Clinical Cardiac Pacing, Defibrillation and Resynchronization Therapy 4th Edition: Expert Consult Premium Edition - Enhanced Online Features and Print

Clinical Cardiac Pacing, Defibrillation, and Resynchronization Therapy fourth edition KENNETH A. ELLENBOGEN, MD Kontos Professor of Medicine Chairman, Division of Cardiology Director, Clinical Electrophysiology Laboratory Medical College of Virginia Richmond, Virginia

G. NEAL KAY, MD Professor, Department of Medicine Director, Clinical Electrophysiology Section The University of Alabama at Birmingham Birmingham, Alabama

CHU-PAK LAU, MD Director, Cardiac Health Heart Centre Honorary Clinical Professor Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong, China

BRUCE L. WILKOFF, MD Director, Cardiac Pacing and Tachyarrhythmia Devices Robert and Suzanne Tomsich Department of Cardiovascular Medicine Institute Medical Information Officer Sydell and Arnold Miller Family Heart and Vascular Institute Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, Ohio

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

CLINICAL CARDIAC PACING, DEFIBRILLATION, AND RESYNCHRONIZTION THERAPY Copyright © 2011, 2007, 2000, 1995 by Saunders, an imprint of Elsevier Inc.

978-1-4377-1616-0

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier. com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data Clinical cardiac pacing, defibrillation, and resynchronization therapy / [edited by] Kenneth A. Ellenbogen … [et al.].—4th ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4377-1616-0 (hardcover : alk. paper)  1.  Cardiac pacing.  2.  Defibrillators.  I.  Ellenbogen, Kenneth A. [DNLM:  1.  Cardiac Pacing, Artificial.  2.  Cardiac Resynchronization Therapy.  3.  Defibrillators, Implantable.  4.  Pacemaker, Artificial. WG 168] RC684.P3C54 2011 617.4′120645—dc23 2011026279

Executive Publisher: Natasha Andjelkovic Developmental Editor: Janice M. Gaillard Publishing Services Manager: Patricia Tannian Project Manager: Sarah Wunderly Design Direction: Ellen Zanolle

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To my wife and family, Phyllis, Michael, Amy, and Bethany, for their patience, support, and love. To my parents, Roslyn and Leon, who instilled in me a thirst for learning. To my students, teachers, and colleagues, who make each day an absolute delight. KAE

To my teachers, colleagues, and students, who have taught me about cardiac pacing. I am also indebted to the many members of the industry who have dedicated their professional careers to the design and improvement of pacing technology. These individuals have greatly improved the therapy that clinicians can offer to their patients, undoubtedly resulting in an improvement in their lives. Perhaps most important, this book is dedicated to my wife, Linda, for her patience and understanding during its preparation. GNK

To my wife and family, Carven, Yuk-Fai, and Yuk-Ming, for their understanding, support, and love. To my teachers, patients, and colleagues, who are my source of inspiration and encouragement. CPL

To my wife, Ellyn, children Jacob and Margaret, Benjamin and Kara, Ephram and Kay for their godly and inspirational patience and support. To my grandchildren, Isabelle and Tobias, for life, hope, and love. To my parents, Harvey and Glenna, for their unconditional love and insights. To Yeshua, the Messiah, for His salvation, and His sustaining covenant love. And for the inspiration of His words in Proverbs 15:2: “The tongue of the wise makes knowledge acceptable.” May the words of this book prove to be wise and useful to the student of cardiac pacing, defibrillation, and heart failure device therapy. BLW

CONTRIBUTORS Amin Al-Ahmad, MD Assistant Professor Department of Cardiovascular Medicine Stanford University School of Medicine Director, Cardiac Electrophysiology Laboratory Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices Angelo Auricchio, MD, PhD Professor of Cardiology University of Magdeburg Magdeburg, Germany Director, Clinical Electrophysiology Unit Fondazione Cardiocentro Ticino Lugano, Switzerland Basic Physiology and Hemodynamics of Cardiac Pacing Bryan Baranowski, MD Associate Staff Section of Cardiac Pacing and Electrophysiology Heart and Vascular Institute Cleveland Clinic Cleveland, Ohio Imaging of Implantable Devices Gust Bardy, MD Clinical Professor of Medicine University of Washington Director, Seattle Institute for Cardiac Research Seattle, Washington Subcutaneous Implantable Cardioverter-Defibrillators Peter H. Belott, MD, FACC, FHRS Director of Electrophysiology Sharp Grossmont Hospital La Mesa, California Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation Janneke Berecki-Gisolf, MD, PhD Senior Research Fellow Monash University Accident Research Centre Melbourne, Victoria, Australia Pacing in Neurally Mediated Syncope Syndromes Paola Berne, MD Senior Fellow Department of Cardiology Electrophysiology Section Thorax Institute Hospital Clínic de Barcelona Barcelona, Spain ICD Therapy in Channelopathies Josep Brugada, MD, PhD, FESC Professor of Medicine Barcelona University Medical Director, Hospital Clínic de Barcelona Barcelona, Spain ICD Therapy in Channelopathies

Mina K. Chung, MD Associate Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, Ohio Imaging of Implantable Devices Joshua M. Cooper, MD Assistant Professor of Medicine University of Pennsylvania Attending Cardiac Electrophysiologist Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Engineering and Construction of Pacemaker and ICD Leads Ann M. Crespi, PhD Senior Principal Scientist Department of Battery Research Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators George H. Crossley III, MD Clinical Professor of Medicine University of Tennessee College of Medicine Chief, Cardiac Services Baptist Hospital Nashville, Tennessee Pacemaker, Defibrillator, and Lead Codes, and Headers J. Kevin Donahue, MD Associate Professor Department of Medicine, Biomedical Engineering, Physiology & Biophysics Case Western Reserve University Clinical Cardiac Electrophysiologist The MetroHealth System Cleveland, Ohio The Biologic Pacemaker Derek J. Dosdall, PhD Assistant Professor Department of Internal Medicine Division of Cardiology University of Utah School of Medicine Adjunct Assistant Professor Department of Bioengineering University of Utah Adjunct Assistant Professor Department of Animal, Dairy, and Veterinary Sciences Utah State University Salt Lake City, Utah Cardiac Electrical Stimulation Kenneth A. Ellenbogen, MD Kontos Professor of Medicine Chairman, Division of Cardiology Director, Clinical Electrophysiology Laboratory Medical College of Virginia Richmond, Virginia Pacing for Atrioventricular Conduction System Disease; Interventional Techniques for Device Implantation

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Contributors

Andrew E. Epstein, MD, FAHA, FACC, FHRS Professor of Medicine University of Pennsylvania Chief, Cardiology Section Philadelphia VA Medical Center Philadelphia, Pennsylvania Troubleshooting of Implantable Cardioverter-Defibrillators Laurence M. Epstein, MD Associate Professor of Medicine Harvard Medical School Chief, Arrhythmia Service Director, Electrophysiology and Pacing Laboratory Brigham and Women’s Hospital Boston, Massachusetts Engineering and Construction of Pacemaker and ICD Leads Derek V. Exner, MD, MPH, FRCPC, FACC, FHRS Professor University of Calgary Canada Research Chair, Cardiovascular Clinical Trials Medical Director, Arrhythmia Program Libin Cardiovascular Institute of Alberta Calgary, Alberta, Canada Clinical Trials of Defibrillator Therapy Jeffrey M. Gillberg, MSEE Research Director Bakken Fellow Medtronic, Inc. Minneapolis, Minnesota Sensing and Detection Anne M. Gillis, MD, FRCPC Professor of Medicine University of Calgary Calgary, Alberta, Canada Pacing for Sinus Node Disease Andrew A. Grace, MBChB, PhD Research Group Head University of Cambridge Consultant Cardiologist Papworth Hospital Cambridge, United Kingdom Subcutaneous Implantable Cardioverter-Defibrillators Henry Halperin, MD, MA Carver Professor of Medicine Johns Hopkins School of Medicine Baltimore, Maryland Electromagnetic Interference and CIEDs Haris M. Haqqani, MBBS(Hons), PhD Senior Lecturer School of Medicine The University of Queensland Consultant Electrophysiologist The Prince Charles Hospital Brisbane, Queensland, Australia Engineering and Construction of Pacemaker and ICD Leads David Hayes, MD Medical Director, Affiliated Practice Network Mayo Clinic Mayo College of Medicine Rochester, Minnesota Ethical Issues

Margaret Hood, MBChB Cardiologist Auckland City Hospital Auckland, New Zealand Subcutaneous Implantable Cardioverter-Defibrillators Henry H. Hsia, MD Associate Professor of Medicine Stanford University School of Medicine Associate Director, Electrophysiology Laboratory Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices Raymond E. Ideker, MD, PhD Jeanne V. Marks Professor of Medicine Professor Departments of Biomedical Engineering and Physiology University of Alabama at Birmingham Birmingham, Alabama Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms Carsten W. Israel, MD Associate Professor of Medicine and Cardiology Department of Cardiology Division of Electrophysiology J. W. Goethe University Frankfurt, Germany Chief of Cardiology Evangelical Hospital Bielefeld Bielefeld, Germany Clinical Trials of Atrial and Ventricular Pacing Modes Bharat K. Kantharia, MD, FRCP, FAHA, FACC, FESC, FHRS Professor of Medicine Director, Cardiac Electrophysiology Training Program The University of Texas-Health Science Center at Houston Director, Cardiac Electrophysiology Laboratories Heart and Vascular Institute–Memorial Hermann Hospital Houston, Texas Approach to Pulse Generator Changes Karoly Kaszala, MD, PhD Assistant Professor of Cardiology Virginia Commonwealth University School of Medicine Director, Cardiac Electrophysiology Hunter Holmes McGuire VAMC Richmond, Virginia Electromagnetic Interference and CIEDs G. Neal Kay, MD Professor of Medicine Director, Cardiac Electrophysiology Section Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama Cardiac Electrical Stimulation Paul Khairy, MD, PhD, FRCPC Associate Professor Department of Medicine University of Montreal Canada Research Chair, Electrophysiology and Adult Congenital Heart Disease Director, Montreal Heart Institute Adult Congenital Center Montreal, Quebec, Canada Sensing and Detection



Daniel B. Kramer Teaching Fellow in Medicine Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories Steven P. Kutalek, MD Associate Professor of Medicine Director, Cardiac Electrophysiology Associate Chief, Division of Cardiology Drexel University College of Medicine Philadelphia, Pennsylvania Approach to Pulse Generator Changes Rachel Lampert, MD Associate Professor Yale University School of Medicine Attending Physician Yale New Haven Hospital New Haven, Connecticut Ethical Issues Chu-Pak Lau, MD Director, Cardiac Health Heart Centre Honorary Clinical Professor Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong, China Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring; Leadless Pacing Concepts Kathy L. Lee, MBBS, FRCP, FACC Honorary Clinical Assistant Professor Medical School University of Hong Kong Hong Kong, China Leadless Pacing Concepts Charles J. Love, MD Professor of Medicine Director, Cardiac Rhythm Device Services Division of Cardiovascular Medicine The Ohio State University Medical Center Columbus, Ohio Pacemaker Troubleshooting and Follow-up William H. Maisel, MD, MPH Associate Professor of Medicine Harvard Medical School Director, Pacemaker and ICD Service Beth Israel Deaconess Medical Center Boston, Massachusetts Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories Saman Nazarian, MD Assistant Professor of Medicine Johns Hopkins University School of Medicine Director, Ventricular Arrhythmia Ablation Service Johns Hopkins Hospital Baltimore, Maryland Electromagnetic Interference and CIEDs

Contributors

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Mark J. Niebauer, MD, PhD Assistant Professor Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Staff Physician Cleveland Clinic Cleveland, Ohio Defibrillation Testing, Implant Testing, And Relation to Empiric ICD Programming Marco V. Perez, MD Clinical Instructor Stanford University School of Medicine Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices Robert Andrew Pickett, MD Physician St. Thomas Research Institute St. Thomas Heart at Baptist Hospital Nashville, Tennessee Pacemaker, Defibrillator, and Lead Codes, and Headers Stephen M. Pogwizd, MD Featheringill Endowed Professor in Cardiac Arrhythmia Research Professor of Medicine, Physiology & Biophysics, and Biomedical Engineering Director, Center for Cardiovascular Biology Associate Director, Cardiac Rhythm Management Laboratory University of Alabama at Birmingham Birmingham, Alabama Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms Frits W. Prinzen, PhD Professor of Physiology Maastricht University Maastricht, the Netherlands Basic Physiology and Hemodynamics of Cardiac Pacing François Regoli, MD, PhD Attending Physician, Cardiologist Fondazione Cardiocentro Ticino Lugano, Switzerland Basic Physiology and Hemodynamics of Cardiac Pacing Dwight W. Reynolds, MD Professor of Medicine Chief, Cardiovascular Section University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation Michael P. Riley, MD, PhD Assistant Professor of Medicine Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Troubleshooting of Implantable Cardioverter-Defibrillators Anthony Rorvick, BS Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators

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Contributors

Elizabeth Vickers Saarel, MD Associate Professor University of Utah Director, Electrophysiology Primary Children’s Medical Center Salt Lake City, Utah Imaging of Implantable Devices

Warren M. Smith, MBChB Honorary Clinical Associate Professor in Medicine University of Auckland Cardiologist Auckland City Hospital Auckland, New Zealand Subcutaneous Implantable Cardioverter-Defibrillators

Leslie A. Saxon, MD Clinical Scholar and Chief Division of Cardiovascular Medicine Keck School of Medicine University of Southern California Los Angeles, California Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Bruce S. Stambler, MD Professor of Medicine Case Western Reserve University Cleveland, Ohio Pacing for Atrioventricular Conduction System Disease

Craig L. Schmidt, PhD Senior Director, Energy Systems Research Medtronic Energy and Component Center Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators Gerald A. Serwer, MD Professor of Pediatrics University of Michigan Attending Pediatric Cardiologist University of Michigan Congenital Heart Center Ann Arbor, Michigan Pediatric Pacing and Defibrillator Use Robert S. Sheldon, BSc, MD, PhD Professor of Cardiac Sciences University of Calgary Senior Vice President of Research Alberta Health Services Calgary, Alberta, Canada Pacing in Neurally Mediated Syncope Syndromes Richard B. Shepard Emeritus Professor, Cardiovascular Surgery University of Alabama at Birmingham Birmingham, Alabama Cardiac Electrical Stimulation Ira Shetty, MD Clinical Assistant Professor Loyola University Medical Center Maywood, Illinois Pediatric Pacing and Defibrillator Use Chung-Wah Siu, MD Clinical Assistant Professor Department of Medicine University of Hong Kong Hong Kong, China Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring Paul M. Skarstad, PhD Senior Director of Research (Retired) Medtronic Energy and Component Center Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators

Marc Strik, MD PhD Student Department of Physiology Maastricht University Maastricht, the Netherlands Basic Physiology and Hemodynamics of Cardiac Pacing Michael O. Sweeney, MD Associate Professor of Medicine Harvard Medical School Cardiac Pacing and Defibrillation Cardiac Arrhythmia Service Brigham and Women’s Hospital Boston, Massachusetts Troubleshooting of Biventricular Devices Charles D. Swerdlow, MD, FACC, FAHA, FHRS Clinical Professor of Medicine Department of Cardiology Cedars Sinai Heart Institute David Geffen School of Medicine University of California Los Angeles Los Angeles, California Sensing and Detection Sandeep Talwar, MD, PhD, FRCP Senior Electrophysiology Fellow Division of Cardiology University of Utah Salt Lake City, Utah Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators Patrick J. Tchou, MD Associate Section Head, Cardiac Electrophysiology and Pacing Department of Cardiovascular Medicine Heart and Vascular Institute Cleveland Clinic Cleveland, Ohio Defibrillation Testing, Implant Testing, And Relation to Empiric ICD Programming Hung-Fat Tse, MD William MW Mong Professorship in Cardiology Academic Chief, Cardiology Division Department of Medicine Queen Mary Hospital The University of Hong Kong Hong Kong, China Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring



Mintu P. Turakhia, MD, MAS Instructor of Medicine Stanford University School of Medicine Director of Cardiac Electrophysiology Veterans Affairs Palo Alto Health Care System Stanford, California Timing Cycles of Implantable Devices Darrel F. Untereker, PhD Vice President of Corporate Research and Technology Strategic and Scientific Operations Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators Niraj Varma, MA, DM, FRCP Consultant Cardiac Electrophysiologist Heart and Vascular Institute Cleveland Clinic Cleveland, Ohio Follow-up Monitoring of Cardiac Implantable Electronic Devices Gregory P. Walcott, MD Associate Professor of Medicine University of Alabama at Birmingham Birmingham, Alabama Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms Paul J. Wang, MD Professor of Medicine Stanford University School of Medicine Director, Cardiac Arrhythmia Service and Cardiac Electrophysiology Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices

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Oussama Wazni, MD Assistant Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Director, Research Development Director, Out Patient Department, Cardiac Electrophysiology Cleveland Clinic Cleveland, Ohio Prevention and Management of Procedural Complications; Techniques and Devices for Lead Extraction Bruce L. Wilkoff, MD Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Director, Cardiac Pacing and Tachyarrhythmia Devices Medical Information Officer Heart and Vascular Institute Cleveland, Ohio Prevention and Management of Procedural Complications; Techniques and Devices for Lead Extraction Seth J. Worley, MD Section Chief for Research Lancaster General Health President and Medical Director Lancaster Heart and Stroke Foundation Lancaster, Pennsylvania Left Ventricular Lead Implantation; Interventional Techniques for Device Implantation Paul C. Zei, MD, PhD Clinical Associate Professor of Medicine Stanford University School of Medicine Director, Cardiovascular Medicine Outpatient Clinics Chief, Clinic Advisory Council Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices

PREFACE It all started with cardiac pacemakers in 1958, but now we have car-

diovascular implantable electronic devices (CIED). Investigations of the electrical stimulation of the heart began long ago, but the truly impressive technological developments of this technology over the past more than 60 years has been the result of intense collaborative efforts of physicians, engineers, allied professionals, and heart rhythm device manufacturers. When we began to collect the information to mentor heart rhythm device professionals for the initial 1995 edition of Clinical Cardiac Pacing we did not have a chapter on implantable defibrillators. We added implantable defibrillators in the second edition (2000), and in the third edition (2007) we added resynchronization therapy. Now we have a fourth edition. Although there is not a new form of therapy, there are still important changes in the technologies and our insights into how they are applied. There has been a huge increment in the evidence base of how and in whom these devices should be used, and a great maturation of the techniques of implantation and extraction of devices, and management of patients with specific conditions. Many new technologies are discussed, including leadless pacing, and the subcutaneous ICD. Our philosophy in putting together the fourth edition remains the same as that of our first three editions. We have planned this book to emphasize the science of cardiac pacing, implantable defibrillation, and cardiac resynchronization therapy, and to underline the importance of the fact that it is an interdisciplinary field. Physicians are part of a large web of health professionals who need increasing amounts of information about implantable devices. We have a web site with this edition that includes figures and movies not included in the paper version of our text, as well as much additional material. All of the figures from the text are included and available for download from this web site. We have sought to meet the needs of many with this textbook. Clinicians, scientists, nurses, technicians, and engineers will find the information in these pages practical, authoritative, and helpful in better understanding this therapy. We are excited about the opportunity to present this material in a comprehensive scientific manner, and in doing so we stand on the shoulders of giants in the field of heart rhythm devices. Sy Furman wrote the initial edition’s foreword, and for that affirmation we are extremely thankful. We are more in debt to his legacy of innovation, problem solving, always asking more questions, and, finally, his commitment to educating any and all who

demonstrate interest. He will always be greatly missed and remind us of our debt to all our colleagues, physicians, engineers, nurses, and technicians. We also owe a great debt of gratitude to Serge Barold and particularly to his singularly important text, Modern Cardiac Pacing, published in 1985 by the Futura Publishing Company. Each of us learned more about cardiac pacing from this textbook than from any mentor. It is hard to give credit to some and not others, but clearly there are so many others and also the giants that came before them. It is our hope that this edition will continue to mentor the next generation of heart rhythm professionals. We gratefully acknowledge the invaluable assistance and encouragement of Natasha Andjelkovic and Janice Gaillard of the Health Sciences Division of Elsevier for all their help in keeping the fourth edition on track. We owe a great debt of gratitude to our colleagues and fellows from the Medical College of Virginia and the McGuire Veterans Affairs Medical Center, the University of Alabama, The University of Hong Kong and Queen Mary Hospital, and the Cleveland Clinic for their patience and support in shouldering the extra workload that allowed us to finish our chapters and editing on time. Most important, we cannot thank enough our many contributors and their colleagues, who labored extensively, often taking time from family and other projects, to finish their chapters. This large group of individuals deserves all the credit and thanks for making the fourth edition possible. Our wonderful secretaries, Vera Wilkerson (Virginia Commonwealth University/Medical College of Virginia), Monica Crosby (Cleveland Clinic), Jenny To (The University of Hong Kong), and Dorothy Welch (University of Alabama) were invaluable for their contributions to help complete this project. This textbook is designed to be a functional tool and reference, helping clinicians, scientists, and engineers make the decisions that improve patients’ lives every day. It is our desire that this book serve as a valuable resource to all of these people for many years to come. Kenneth A. Ellenbogen, MD G. Neal Kay, MD Chu-Pak Lau, MD Bruce L. Wilkoff, MD

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VIDEO CONTENTS Introduction Bruce L. Wilkoff, MD 9 Basic Physiology and Hemodynamics of Cardiac Pacing 1. 3D electroanatomical mapping in a patient with left bundle branch block QRS morphology 2. Animated 3D reconstruction of the left ventricular wall with myocardial strain 21 Permanent Pacemaker and Implantable CardioverterDefibrillator Implantation 3. Catheter Delivery of a Fixed Extended Screw in Lead to Coronary Sinus Os 4. Catheter Delivery of a Fixed Extended Screw in Lead 5. Removal of a Fixed Extended Screw in Lead in the Atrium 22 Left Ventricular Lead Implantation 6. Intracardiac View of Coronary Sinus Os and Thebesian Valve 7. Intracardiac View of the Thebesian Valve and Its Fenestrations 8. Intracardiac View of the Right Atrium from the IVC Including the Coronary Sinus Os and Thebesian Valve 9. Rotating Intracardiac View of the Right Atrium from the IVC Including the Coronary Sinus Os and Thebesian Valve 10. Intracardiac View of a White and Floppy Thebesian Valve 11. Intracardiac View of a Tattered Thebesian Valve 12. Intracardiac View of an Occlusive Balloon Inflation in the Coronary Sinus Os 13. Intracardiac View of Insertion and Occlusion of the Coronary Sinus with a Venography Catheter 14. Intracardiac View of a Double Coronary Sinus OS and Thebesian Valve 15. Intracardiac View of Coronary Sinus Os and Thebesian Valve with Only Free Access from Inferior Direction 16. Intracardiac View of Coronary Sinus Os and Tricuspid and Thebesian Valves with Attempted EP Catheter Access from Above 17. Intracardiac View of Coronary Sinus Os and Tricuspid and Thebesian Valves with Successful EP Catheter Access from Below 18. Intracardiac View of Coronary Sinus OS and Thebesian Valve with Attempted EP Catheter Access from Above 19. Intracardiac View of a Complicated Thebesian and Tricuspid Valve 20. Intracardiac View of Coronary Sinus Os with Early Branching 21. Intracardiac View of Coronary Sinus Os with Early Branching

22. Intracardiac View of Catheters in the Coronary Sinus and Through the Tricuspid Valve 23. Fluoroscopic Venogram of the Main Coronary Sinus and Mid-CS Valve 24. Fluoroscopic Advancement of a Decapolar EP Catheter into the Coronary Sinus 25. 3D image of the Cardiac Venous Anatomy 26. Occlusive Venography of Coronary Sinus LAO 30 27. Occlusive Venography of Coronary Sinus Anteroposterior Projection 28. Occlusive Venography of Coronary Sinus RAO 30 Projection 29. Sheath and Wire Subselected into Anterolateral Branch 30. Sheath and Wire Subselected into Posterior Vein Branch 31. Subvalvular Pouch Mimicking Coronary Sinus Os 32. True Coronary Sinus Venogram 33. Final Lead Position in Posterior-Lateral Branch 24 Approach to Pulse Generator Change 34. Abdominal ICD Pulse Generator with Subcutaneous Patch Electrode 35. Abdominal ICD Pulse Generator with Previously Cut and Capped Additional Electrode 36. Patient from Previous Case After Extraction and Reimplantation 37. Alternative Approach to an Occluded Subclavian Vein 38. Total Occlusion of the Left Subclavian Vein with Reconstitution via the Right Side 25 Prevention and Management of Procedural Complications 39. Transesophageal Echo of Large Right Atrial Vegetation on an ICD Lead 40. Transesophageal Echo of Large Right Atrial Vegetation on a Pacemaker Lead 41. Subclavian Vein Venography and Lead Fractures 26 Techniques and Devices for Lead Extraction 42. Needles-Eye-Snare Extraction of Fractured Ventriculo-Jugular Shunt 43. Fluoroscopy of Embolized Telectronics Accufix Wire 44. Laser Lead Extraction of Single Coil ICD Lead Special Presentation 45. ICD Implantation: Implantation and Management of Complications (PowerPoint presentation)

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Cardiac Electrical Stimulation G. NEAL KAY  |  DEREK J. DOSDALL  |  RICHARD B. SHEPARD

Pathologic cardiac conditions such as asystole, bradycardia, conduc-

tion block, and dyssynchronous contraction may lead to significant morbidity and mortality. One of the most influential and effective medical device therapies developed in the last century is the cardiac pacemaker and implantable cardioverter-defibrillator (ICD). The lives of millions of patients have been improved and extended through the use of pacing techniques that regulate heart rate and improve cardiac output. Direct electrical stimulation of excitable cardiac tissue causes a change in the transmembrane potential of resting cardiac cells. If the transmembrane potential is raised to a certain level, an action potential is initiated in the cells and spreads to adjacent working myocardial cells. The action potential induces mechanical contraction of the cardiac cells that spreads throughout the heart as a self-propagating wavefront. This chapter reviews the fundamental concepts of artificial electrical cardiac stimulation, including the cellular aspects of myocardial stimulation, the influence of external current on cardiac tissue, waveform and electrode considerations, clinical applications and considerations, and ongoing research regarding cardiac stimulation.

Concepts Related to Electrical Stimulation of the Heart STATIC ELECTRIC CHARGE AND ELECTRIC FIELDS Physical objects may acquire an electric charge when they have a net excess or deficit of electrons relative to the number of protons. When the number of electrons exceeds the number of protons, the object is said to have a negative charge, whereas a net deficit of electrons results in the object acquiring a positive charge. An electrically charged object is surrounded by an electric field such that charged objects act at a distance on other objects having similar or opposite charge. The strength of the electric field is related to the magnitude of its charge. A gravitational field also acts at a distance, but an electric field has an important difference, polarity. Thus, electric fields have directionality with the convention that field lines are drawn away from positively charged and toward negatively charged objects. The electric fields surrounding charged objects interact with each other such that the presence of two electrically charged objects results in a force that either attracts the two objects (if they have opposite charges) or repels the two objects (if they have the same qualitative charge). This attractive or repulsive force acts at a distance, not requiring that the charged objects be in contact, and the attractive or repulsive force (F) is given by Coulomb’s law:

F=k

Q1 Q2 r2

where Q1 and Q2 are the magnitude of the charges (measured in coulombs), r is the distance separating the charged objects, and k is a 1 constant equal to with ε being the permittivity of free space. 4πε According to Coulomb’s law, the force attracting or repelling charged objects increases with the magnitude of charge and decreases with the square of the distance that separates them. Potential Difference Voltage is the electrical potential energy possessed by a charge by virtue of its position in space. A charged object in space has potential energy

because of the forces that other charges exert on that object. When two charged objects repel one another, energy is required to move either object closer to the other, thereby increasing the potential energy. However, if the charged object is attracted to another charged object, potential energy will be converted into kinetic energy when either charge moves closer to the other. Thus, the force generated by the interaction of electrical charge is electromotive, tending to move charged objects. Voltage is the potential energy per unit charge for a charge in an electric force field. Thus, in order to move a charge from point A to point B, the work required (measured in joules) is calculated by multiplying the charge, Q, by the voltage difference between points A and B, VAB. Because voltage is potential energy per unit of charge, it is measured in terms of joules/coulomb, as follows:

1 volt = 1 joule/coulomb

When one refers to “voltage,” the reference is to a difference in potential between two points in space. Electric Current An electric current, I, is present when there is a movement of electric charge. Although electric charge may move through several mechanisms, for clinical purposes, electric charge is usually carried by the flow of electrons through a wire (e.g., pacemaker lead) or by the movement of ions in blood, interstitial fluid, across cell membranes, or within the cytoplasm of cells. By historical convention, current is considered to flow in the direction that positive charges would move. In reality, however, an electric current in a wire is carried by the movement of electrons that are negatively charged. For clarity in this chapter, current is stated in terms of electron or ion motion. Because electric current is the movement of charge, it is measured in terms of coulombs per second (It = dQ/dt), with 1 ampere of current equal to the movement of 1 coulomb/sec. The electromotive force for cardiac pacemakers or ICDs is determined by the chemistry of a battery. For lithium-iodine batteries at beginning of life, the chemical reaction generates approximately 2.8 volts of electromotive force. The total amount of charge that is available in the battery is measured in terms of the amount of current that can be provided for a given unit of time. For pacemaker or ICD batteries the amount of charge that can be stored in the battery is measured in terms of ampere-hours, with 1 A-hr equal to 3600 coulombs of charge. ELECTRIC CIRCUIT An electric circuit is an electric charge–conducting pathway that ends at its beginning. For electric circuits involved in myocardial stimulation by pacemakers or ICDs, the voltage difference in the circuit is provided by a battery. The difference in voltage generated by the battery results in a flow of charge (current) from the pulse generator through the conductors in the leads, electrodes, extracellular electrolytes, cell membranes with highly regulated transmission of charged ions in both directions through the membrane, and intracellular ions and charged molecules. As current flows through the complete electric circuit, the net voltage change must be zero (Kirchoff ’s voltage law). Thus, the electromotive force (voltage) generated by the battery (an increase in potential energy) must be completely dissipated (a decrease in potential energy) as current flows through all the elements of the circuit to end at the battery.

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SECTION 1  Basic Principles of Device Therapy

Electric circuits in the clinical practice of pacing have multiple elements, including the pulse generator battery, the lead conductor(s), the electrodes, the myocardium, and blood within the great veins and cardiac chambers. All these elements introduce opposition to the flow of current. Series Circuit In a series circuit, or circuit module, the elements are connected so that current must flow sequentially through each element in the circuit. Thus, the current flowing through all elements in series is the same, with the voltage difference decreasing sequentially as it passes through each element in the circuit. Parallel Circuit In a parallel circuit, two or more elements are joined at each end to a common conductor (node in the circuit). Therefore, the potential difference is the same before each element and after each element, and current will flow from one of the common conductors to the other through any or all of the elements. The degree of current flow in each element is inversely related to the factors that oppose the flow of electric charge in that element. At any node (junction) in an electric circuit, the sum of currents flowing into that node is equal to the sum of currents flowing out of that node (Kirchoff ’s current law). Most biologic circuits are made of various combinations of series and parallel modules or subcircuits. For example, because of electrochemical effects, an electrode placed in the heart may act as a capacitor in parallel with a resistor, both in series with the lead joining the pulse generator to the electrode. ELECTRODE POLARITY All defibrillator and pacemaker electric circuits have both a positively charged electrode (the anode) and a negatively charged electrode (the cathode). The negatively charged cathode is typically the tip electrode on a pacing lead. Electrons from the pulse generator flow through the cathode-tissue interface and return to the anode, which may be located on a pacing lead or the pulse generator casing. The terminology used for electrode polarity may be confusing as applied to lead electrodes and the electrodes of a battery. The electrode in a battery at which oxidation occurs (e.g., oxidation of lithium to yield Li+ plus an electron, e−) is the battery anode. The battery anode, by continuing oxidation, furnishes electrons to the circuit external to it. Therefore, in contradistinction to the terminology used for pacing leads, the terminal of the battery where electrons are provided to the circuit is the battery anode. From the battery anode, electrons flow through the circuitry and eventually enter the pacemaker lead electrode that is in contact with the myocardium. This electrode, receiving electrons from the pulse generator and furnishing electrons to the tissue, is the lead cathode. The return electrode located in the heart or on the pulse generator casing is the lead anode. It collects electrons from the tissue and returns them through the pulse generator circuitry to the positive electrode of the battery, the battery cathode, where reduction occurs (e.g., I2 + 2e− yields 2I−). The consistency in the terminology is that, when oxidation occurs, it occurs at an anode, and in the circuitry, an anode connects to a cathode that subsequently connects to another anode, and so on. OPPOSITION TO FLOW OF ELECTRIC CURRENT In cardiac pacing and defibrillation, several elements in the electric circuit oppose the flow of electric current. As current flows through some of these elements, such as the conductor wires in the leads and pulse generator, the opposition to current flow results in energy being lost as heat. These elements are known as ohmic, and the opposition to current flow is called resistance (R). The instantaneous voltage developed across a perfect resistor is linearly proportional to the instantaneous current flow through the resistor. If a steady voltage across the

resistor is represented by V, the current by I, and an unchanging resistance by R, the relationship is expressed as follows in Ohm’s law:

V = IR

In reality, when all the elements of a cardiac pacing circuit are considered, these factors are much more complex than can be represented by Ohm’s law alone. These other factors include capacitance and inductance. For calculations involving a pulsed (e.g., pacemaker stimulus) or an alternating current (AC) circuit that contain reactive elements (e.g., electrodes in contact with electrolytes), the term impedance (Z) must be used in place of resistance. Impedance is a vector sum of resistance (R) and reactance (X). The following sections discuss the major components of reactance. CAPACITANCE As mentioned earlier, current can be carried in different ways. Electrolyte is used as a generic term for the electrically conductive extracellular and intracellular fluids near pacemaker or defibrillator electrodes and elsewhere in the heart and blood vessels. The electrolyte conducts ions but not electrons. The difference between the conduction of electric currents by electrolytic fluids and the flow of electrons over metal wires is crucial to pacing. Because a negatively charged pacing electrode in contact with the endocardium is surrounded by blood and interstitial fluid, positively charged ions move toward that electrode during a pacing stimulus. This results in the phenomenon of polarization, which develops rapidly and dissipates slowly after the end of the stimulus. The opposite effect occurs on the positively charged anode. This effect of ions moving to oppose the flow of electric current has the effect of a capacitor in the circuit. A capacitor is an object that stores energy in an electric field by holding positive charges apart from closely approximated negative charges. A capacitor requires a material or space between the layers of negative and positive charges that is normally nonconducting (the dielectric). A cell membrane, although leaky, acts as a capacitor by separating the negatively charged inside of the cell from the more positively charged outside. Cell membranes have very high capacitance per unit area of cell membrane. The interface between a pacing electrode and the charged electrolytes that surround the electrode at its surface in the myocardial tissue acts, in part, as a capacitor. The terms Helmholtz capacitor and Helmholtz capacitance are used in this chapter for capacitor-like effects that occur at pacemaker and defibrillator electrode-electrolyte interfaces. Capacitance (C) is the term that specifies, for a given voltage applied across a capacitor, how much electrical charge (Q) can be stored by the capacitor. If V represents a steady voltage applied across the capacitor, then Q = CV. (If E is used instead of V as the symbol for electric potential, the relationship may be expressed as Q = CE.) The unit for capacitance is the farad. One farad is the capacitance of a capacitor that, on being charged to 1 volt, will have stored 1 coulomb of charge. Again, a coulomb is the amount of charge delivered by 1 ampere flowing for 1 second. Coulombs delivered can be expressed as follows:

t

Q t = ∫ i t dt 0

in which Qt is the total charge delivered between time 0 and time t, and it is the instantaneous current at each time segment between time t 0 and time t. The integral ∫ i t dt is the net area under the instantaneous 0 current-versus-time plot. INDUCTANCE When an alternating current flows through a wire, a magnetic field surrounding the wire is induced. An inductor is an object that stores or releases energy in or from a changing magnetic field. The voltage difference across an inductor is proportional to the rate of change of current flowing through the inductor. Energy is stored during the formation of the magnetic field and is released when the magnetic field decreases or disappears. Inductance is the term that specifies the



1  Cardiac Electrical Stimulation

relationship between the voltage across an inductor and the rate of change of current traversing the inductor. The magnitude of the inductance can be represented by the symbol L. If Vt represents the instantaneous voltage across the inductor, and iL represents the instantaneous current flowing through the inductor, the relationship is given by the following equation: di L 1 t or i L = ∫ v t dt dt L 0 Note that the voltage across the inductor is directly proportional to the rate of change of current flowing through the inductor. Cell membrane currents have some of the current- and voltage-versus-time characteristics of an inductance in parallel with a capacitance.1 These inductancelike effects are related to the timing and magnitude of potassium ions moving into and out of the cell.2

vt = L

REACTANCE (CAPACITANCE AND INDUCTANCE) For reactive elements connected in series, net reactance is the scalar sum of inductive reactance (positive in the mathematical complex plane) and capacitive reactance (negative in complex plane). Pure reactance values depend on the rates of change of current and voltage, whereas pure resistance values do not. Phenomena of this type are caused by differences in the timing of the peaks (phase angles) of the voltages or currents in the various reactive components. These reactive effects can be important in biventricular pacing threshold measurements (see later discussion). The component of reactance that is most relevant to both pacing electrodes and cell membranes is capacitance, with inductance being much less important. For example, the cardiac action potential spreading throughout the heart generates a changing magnetic field that transiently stores a very small amount of energy. However, the changing magnetic field generated by spread of the action potential is so small that it is not clinically significant except in the research setting.3 For circuits with resistance R, capacitance C, and inductance L in series, where qt represents the charge accumulated across the capacitance at any time t, and where the current through these combined elements at time t is it, the voltage Vt at time t is described by the following equation: t idt qt di di ∫ 0 v t = i tR + + L or v t = i t R + +L C dt C dt t (remembering that q t = ∫ i t dt and that the voltage across a capacitor 0 qt at time t is ). C These equations indicate that, for an instantaneous current it, the instantaneous voltage across the series circuit is the sum of the effects at that instant in time of the resistance, capacitance, and inductance of the circuit. Note especially that the instantaneous effects are highly t related to the net amount of charge, q t = ∫ i t dt , that has accumulated 0 in the capacitor from time 0 to the instantaneous time t. The equations show that the capacitance effect on the voltage decreases as the capacitance increases. This has clinical relevance in that, for example, the polarization voltage that interferes with autosensing pulse generators decreases as the electrode capacitance increases.

(

)

Cellular Aspects of Myocardial Stimulation THE PHOSPHOLIPID BIMEMBRANE Living cells maintain or regenerate a difference in electric potential across the cell membrane. Excitable tissues such as myocardium respond to electrical stimulation of one or more cells with a wave of electrical depolarization—a transient reversal of the voltage gradient across the membrane—that can propagate from cell to cell. Excitable cells respond to a relatively small applied change in electric potential

5

Phospholipid

Lipid “tail” Phosphate “head” Ion channel

Figure 1-1  The phosphomembrane bilayer of a cardiomyocyte contains ion channels and structures that maintain distinct ion concentrations inside and outside of the cell. Charge pumps maintain an ion concentration gradient across the membrane while ion channels allow for charge in the form of ions to pass through the membrane. The ion current flow causes changes in transmembrane potential and cardiac activation.

difference across the cell membrane by triggering a series of biochemical and biophysical events (described later). These depolarization events result in myocyte contraction. Depolarization propagates along excitable cell membranes, as in the transmission of an action potential along a squid axon, and from myocyte to myocyte through gap junctions. CELL MEMBRANE CHARACTERISTICS Cell membrane characteristics are major determinants of tissue excitability. The membrane of the cardiac myocyte is composed principally of phospholipids, cholesterol, and proteins.4 The membrane phospholipids have a charged polar headgroup and two long hydrocarbon chains arranged as shown in Figure 1-1. The cell membrane comprises two layers of phospholipids with their hydrophobic aliphatic chains oriented toward the central portion of the bilayer membrane and their polar headgroup regions toward the outside boundaries of the membrane. Because the membrane is composed of two layers of phospholipids, the polar regions of the phospholipid molecules interface with the aqueous environments inside and outside the cell. The lipid-soluble hydrocarbon chains are forced away from the aqueous phase to form a nonpolar interior. DETERMINANTS OF THE RESTING TRANSMEMBRANE POTENTIAL Relatively large gradients of individual ion concentrations exist across the cardiac cell membrane.5 The gradient of sodium ions (Na+) across the membrane is approximately 145 millimoles per liter (mmol/L) outside to 10 mmol/L inside. In contrast, the potassium ion (K+) concentration outside the cell is approximately 4.5 mmol/L, whereas the inside concentration is 140 mmol/L. In the absence of a cell membrane, both Na+ and K+ would rapidly move in a direction determined by the concentration gradient. The diffusion force tending to move K+ out of and Na+ into the cell is proportional to the concentration gradients of those ions. The potential energy attributable to the diffusion force (PEd) tending to move K+ out of the cell is given by the following equation:   [K + ]   PEd = RT  ln  + i   [1-1]   [K ]o   where R is the gas constant, T is the absolute temperature, ln is the natural logarithm operator, [K+]i is the concentration of potassium ion inside the cell, and [K+]o is the concentration of potassium ion outside the cell. If the ratio of [K+]i to [K+]o is large, the potential energy across the membrane is large. For each ion species, the difference in concentration between the inside and the outside of the cell results in that ion’s contribution to the difference in electric potential across the cell membrane. In resting cardiac cells, the intracellular cytoplasm has a measured potential of about −90 millivolts (mV), relative to the extracellular

6

SECTION 1  Basic Principles of Device Therapy

fluid. This electric force tends to move positively charged ions such as K+ and Na+ to the inside of the cell and negatively charged ions such as chloride (Cl−) to the outside of the cell in proportion to the potential gradient. The potential energy attributable to the electric force (PEe) tending to move K+ into the cell is expressed as follows: PE e = zFVm



Na+

K+

A

Protein molecules embedded within the cell membrane have numerous functions, including those of being ion channels and signal transducers. The concept of ion channels was proposed in the 1950s by Hodgkin and Huxley.7 However, it was not until the introduction of the patch clamp technique by Neher and Sakmann in 1976 that the properties of these channels could be directly studied.8,9 There are two basic types of ion channels, distinguished by the factors that control opening and closing of the channel. Ion channels at muscle fiber end plates are chemically gated by specific transmitters. The opening of these channels is triggered by the binding of acetylcholine, and their closing is induced by its unbinding. In neuronal axons, conduction is mediated by faster, voltage-gated channels. These channels respond to differences in electric potential between the inside and outside of the

CACNA1C

INa/Ca

NCX1

0

i

Ion Channels

Ca2+

Probable gene SCN5A

ICa.L

Using known values for extracellular K+, Vm(K+) = −90 mV. When Equation 1-3 is solved using Na+ concentrations, a Vm(Na+) of +50 mV is obtained. Therefore, it is the equilibrium potential for potassium ion (not sodium ion) that is the major factor responsible for the resting transmembrane potential. This suggests that the resting membrane is more permeable to K+ than to Na+. To calculate the transmembrane potential when multiple ionic species exist in different concentrations across the membrane, the Goldman constant field equation (modified by Hodgkin and Katz6) is used: + + + + − − − RT   PK [K ]i + PNa [ Na ]i + PCl [Cl ]o + …  Vm =  ln  + + [1-4]  + + −  F   PK [K ] + PNa [ Na ] + PCl [Cl − ] + … where PK+, PNa+, and PCl− are the cell membrane permeabilities for the respective ions. At physiologic concentrations, this equation yields a transmembrane potential of −90 mV (the equilibrium potential for K+). Equation 1-4 describes how resting potentials vary as sodium and potassium ion concentrations are changed. Because there is a passive leak of charged ions through the membrane, the resting potential would not exist at the level of −90 mV unless it were actively maintained. This is accomplished by two active transport mechanisms that exchange Na+ ions for K+ and calcium (Ca2+) ions. One might ask: with all the potassium ions and other positively charged ions in the cell, and with a relatively small amount of negatively charged chloride ions in the cell, how can the interior of the cell be negative with respect to the outside? The answer is that an array of intracellular organic and inorganic anions inside the cell—molecules that do not cross the membrane—carry net negative charges sufficient to make the overall balance of charge negative.

K+

INa

 [K + ]  or, in log base 10 terms, Vm (K + ) = −61.5 log  + i  .  [K ]o 

o

Na+

[1-2]

where z here is the valence (the number of positive or negative electrical charges) of the ion, F is the Faraday constant (96,500 coulombs/ equivalent), and Vm is the transmembrane potential difference (transmembrane voltage, measured in millivolts). During equilibrium, the total of the potential energies from diffusion and electric forces is zero, and no net ionic movement occurs. Therefore, the sum of Equation 1-1 and Equation 1-2 may be set to zero. This yields the Nernst equation, which describes (in measurable electrical units) the potential that must exist for a single ionic species, here K+, to be in equilibrium across the membrane of a resting cardiac cell:  [K + ]  Vm (K + ) = −26.7 ln  + i  [1-3]  [K ]o 

o

Ca2+

IK1

KCNJ2

Ito1

KCND

Ito2

?

IKr

KCHNH2IKCNE2

IKs

KCHQ1IKCNE1

IKp

KCNK?

B Figure 1-2  Ion channels underlie cardiac excitability. A, Key ion channels (and electrogenic transporter) in cardiac cells. K+ channels (green) mediate K+ efflux from the cell; Na+ channels (purple) and Ca2+ channels (orange) mediate Na+ and Ca2+ influx, respectively. The Na+/ Ca2+ exchanger (red) is electrogenic, because it transports three Na+ ions for each Ca2+ ion across the surface membrane. B, Ionic currents and genes underlying the cardiac action potential: top, depolarizing currents as functions of time, and their corresponding genes; middle, ventricular action potential; bottom, repolarizing currents and their corresponding genes. (From Marban E: Cardiac channelopathies. Nature 415:213-218, 2002. ©Nature Publishing Group, http://www.nature.com.)

cell, across the membrane. Voltage-gated channels for sodium, potassium, and calcium appear to operate in similar ways, sharing many of the same structural features. In addition, each type of channel can be subdivided into several subtypes with different conductance or gating properties (Fig. 1-2). VOLTAGE-GATED CHANNELS Voltage-gated channels open in response to an applied electric potential. The source of this voltage can be an action potential propagated from an adjacent cell or the electric field of an artificial pacemaker electrode. If depolarization of the membrane exceeds a threshold voltage, an action potential is triggered, resulting in a complex cascade of ionic currents flowing across the membrane into and out of the cell. As a result of this flow of charge across the membrane, the potential gradient across the membrane changes in a characteristic pattern of events that produce the cardiac action potential (Fig. 1-3).

1  Cardiac Electrical Stimulation

50 Phase 1 Phase 2

–50

Phase 0

0 Threshold

Transmembrane potential (mV)



Phase 3

Phase 4 –100 100

200

300

400

500

Time (msec) Figure 1-3  Microelectrode recording of transmembrane potential (Vm) from left ventricular endocardium of human heart. In phase 0 (depolarization), sodium ions (Na+) rapidly enter the cell through fast channels. In phase 1, the initial repolarization is primarily the result of activation of a transient outward potassium ion (K+) current and inactivation of the fast Na+ current. In phase 2 (plateau), the net current is very small, although the individual Na+, Ca2+, and K+ currents are about an order of magnitude larger. Phase 3 (final repolarization) completes the cycle, with the Na+-K+ pump bringing the membrane potential to a stable point at which inward and outward currents are again in balance. During phase 4, the cell is polarized and gradually undergoes slow depolarization. (From Stokes K, Bornzin G: The electrode-biointerface [stimulation]. In Barold SS [ed]: Modern cardiac pacing. Mt. Kisco, NY, Futra, 1985, pp 33-78.)

Selective membrane-bound proteins (ion channels) determine the passive transmembrane flux of an individual ion species. The transmembrane currents determine or influence cellular polarization at rest, action potential depolarization and repolarization, conduction, excitation-contraction coupling, and myofibril contraction. The channels that regulate transmembrane conductance of Na+ and Ca2+ are voltage gated. The sodium channel is a large protein molecule composed of approximately 1830 amino acids.10 It contains four internally homologous repeating domains, believed to be arranged around a central water-filled pore lined with hydrophilic (“water-loving”) amino acids. It is estimated that there are 5 to 10 Na+ channels per square micrometer (µm2) of cell membrane. When an alteration changes the membrane potential to about −70 to −60 mV (the threshold potential), four to six positively charged amino acids move across the membrane in response to the change in electric field. This causes a change in the conformations of the channel proteins, resulting in opening of the channel. After a single Na+ channel changes to the open conformation, about 104 Na+ ions enter the cell. On depolarization of the membrane, the Na+ channels remain open for less than 1 millisecond (msec). After rapid depolarization of the membrane, the Na+ channel again changes to the closed conformation. In addition to the Na+ channel, specialized proteins are suspended in the cell membrane that have differential selectivity for K+, Ca2+, and Cl− ions, with much different time constants for activation and inactivation. SINOATRIAL AND ATRIOVENTRICULAR NODAL CELLS In contrast to Purkinje fibers and working myocardial cells, sinoatrial (SA) and atrioventricular (AV) nodal cells are characterized by no true resting potential. Following repolarization, the transmembrane potential of the nodal cells reach a minimum of approximately −60 mV. The SA and AV nodal cells have a slow, inward, depolarizing, combined Na+/K+ current known as the “funny” current (If ). These If channels open and cause the transmembrane potential to rise slowly until Ca2+ channels are activated and an action potential is generated. The rate of

7

this rise in transmembrane potential is affected by factors such as autonomic nervous stimulation and hormones. In these nodal structures, depolarization is primarily mediated by inward Ca2+ conductance through specialized Ca2+ channels. There are two types of Ca2+ channels in the mammalian heart. The L-type channels are the major voltage-gated pathway for entry of Ca2+ into the myocyte, and they are heavily modulated by catecholamines.11 The T-type channels contribute to spontaneous depolarization of the cell associated with automaticity (pacemaker currents). The pore of the Ca2+ channel has a functional diameter of about 0.6 nanometers (nm), larger than that of the Na+ channels (0.3-0.5 nm).12 The selectivity for Ca2+ is high, up to 10,000-fold greater than that for Na+ or K+. The key elements are high-affinity binding sites for Ca2+, positioned along a single file pore. “Elution” of a Ca2+ ion occurs when another Ca2+ ion enters and is selectively bound. In normal situations, the SA node has the most pronounced automaticity and highest spontaneous firing rate in the heart. If the SA node is not functioning properly, however, or if block develops between the SA node and the AV node, the AV node will display pacemaker activity at a slightly slower rate than the SA node. In the absence of a pacemaker signal from the AV node, Purkinje fibers will activate at an even slower rate than either the SA or the AV node. MAINTENANCE OF RESTING MEMBRANE POTENTIAL The resting membrane potential is maintained by the pumping of Na+ ions out of the cell and K+ ions into the cell. The Na+,K+—adenosine triphosphatase (ATPase) pump moves three Na+ ions out of the cell in exchange for two K+ ions moved into the cell.13-15 The basic unit of the Na+,K+-ATPase protein (pump) consists of one alpha (α-) and one beta (β-) subunit. The α-subunit is large (1016 amino acids) and spans the entire membrane, whereas the β-subunit is a smaller glycoprotein. There appear to be about 1000 pump sites/µm2 of cardiac cell membrane. The fully activated pump cycles about 50 to 70 times per second (interval of 15-20 msec/cycle). Similarly, the Na+-Ca2+ pump moves three Na+ ions out of the cell in exchange for one Ca2+ ion.16,17 Therefore, both transport mechanisms result in the net movement of one positive charge out of the cell, polarizing the membrane and maintaining a negatively charged interior. The function of both exchange mechanisms depends on the expenditure of energy in the form of high-energy phosphates and is susceptible to interruptions in aerobic cellular metabolism (e.g., during ischemia). THE CARDIAC ACTION POTENTIAL When the voltage gradient across the membrane of a myocyte decreases so that the inside of the cell becomes less negatively charged with respect to the outside of the cell, a critical transmembrane voltage difference is reached, the threshold voltage. At threshold, the cell membrane suddenly undergoes a further depolarization that is out of proportion to the intensity of the applied stimulus. This abrupt change in the potential across the membrane is the start of a cascade of inward and outward currents that together are known as an action potential.18 The cardiac action potential is an enormously complex event and consists of five phases19 (see Fig. 1-3): phase 0, the upstroke phase of rapid depolarization; phase 1, the overshoot phase of initial rapid repolarization; phase 2, the plateau phase; phase 3, the rapid repolarization phase; and phase 4, characterized by a slow, spontaneous depolarization of the membrane in cells with spontaneous pacemaker activity, until the threshold potential is again reached and a new action potential is generated. Phase 0: Rapid Depolarization The upstroke of the action potential is triggered by a decrease in the potential gradient across the membrane to the threshold potential of −70 to −60 mV. On depolarization of the membrane to the less negative threshold voltage, the Na+ channels open, resulting in an influx of

8

SECTION 1  Basic Principles of Device Therapy

positively charged ions (the inward Na+ current) and rapid reversal of membrane polarity. The rate of depolarization in phase 0 ranges from 800 volts per second (V/sec) in Purkinje cells to 200 to 500 V/sec in atrial and ventricular myocytes. In these cells, the inward Na+ current is primarily responsible for phase 0 of the action potential. In SA and AV nodal cells, where the inward Ca2+ current predominates, the upstroke velocity of phase 0 is much lower (20-50 V/sec). Phase 1: Initial Repolarization After voltage-dependent activation of the Na+ current in phase 0, the membrane potential rapidly changes from negative to positive. The increased conductance of Na+ is rapidly followed by voltage-dependent inactivation. Phase 1 is characterized by the transient outward K+ current (IKto). The outward movement of K+ is a major contributor to the various repolarization phases. It is complex and has a number of discrete pathways.20,21 Most K+ currents demonstrate rectification, that is, decreased K+ conductance with depolarization. The K+ currents include the instantaneous inward rectifier K+ current, the outward (delayed) rectifier K+ current, the transient outward currents, and ATP-, Na+-, and acetylcholine-regulated K+ currents. The initial repolarization, however, is mainly the result of activation of a transient outward K+ current and inactivation of the fast inward Na+ current.22 The transient outward K+ current has two components, one voltage gated and the other activated by a local rise in Ca2+. Phase 2: Plateau The net current during the plateau phase is apparently small, although the individual currents (inward Na+ and Ca2+ and outward K+) are each about an order of magnitude larger.23 Among the inward currents are the slowly activating Na+ current, a Ca2+ current, and an Na+-Ca2+ exchange current. Outward currents include a slowly activating K+ current (IKs), a Cl− current, a more rapidly activating K+ current (IKr), an ultra-rapidly activating K+ current (IKur), and the Na+-K+ electrogenic pump. During phase 2 of the action potential, the absolute refractory period, the cardiac cell cannot be excited by an electrical stimulus, regardless of its intensity. Phase 3: Final Repolarization Deactivation of inward Na+ and Ca2+ currents occurs earlier than for the K+ currents, favoring net repolarization of the membrane. When the membrane is sufficiently repolarized, an inward K+ rectifier current is progressively activated, resulting in a regenerative increase in outward currents and an increasing rate of repolarization. Repolarization is also accomplished by the function of the Na+,K+-ATPase pump. The membrane potential eventually becomes stable, so that inward and outward currents are again in balance and the resting potential reestablished. Between the end of the plateau phase and full repolarization, the cell is partially refractory to electrical stimulation. During this period, the relative refractory period, a greater stimulus intensity is required to generate an action potential than required after full recovery of the resting membrane potential. For clinical measurement of myocardial refractoriness, the effective refractory period, stimulation of the heart is usually performed at twice the threshold current, as determined during late diastole. Phase 4: Automaticity and the Conduction System Automaticity is the property of certain cells by which they are able to initiate an action potential spontaneously. It has been known for centuries that the heart can exhibit spontaneous contraction even when completely denervated. Leonardo da Vinci observed that the heart could “move by itself.”24 William Harvey reported that pieces of the heart could “contract and relax” separately.25 Many cells within the specialized conduction system have the potential for automaticity. Not all parts of the heart, however, possess this property. In fact, cells in different areas of the heart have different transmembrane potentials, thresholds, and action potentials. Fast responses are characteristic of ordinary working ventricular muscle cells and His-Purkinje fibers, with resting membrane potentials of −70 to −90 mV and rapid

conduction velocities. Normal SA and AV nodal cells have slow responses, with resting potentials of −40 to −70 mV and slow conduction velocities. Cells, or group of cells, with the fastest rate of spontaneous membrane depolarization during phase 4 are the first to reach threshold potential and initiate a propagated impulse. Therefore, cells with the steepest slope in phase 4 become the heart’s natural pacemaker. Ordinary working myocardial cells usually are not automatic. Normally, depolarization is initiated at the SA node.26,27 Figure 1-4 shows action potentials from different types of cardiac cells.28 Rather than maintaining a stable resting membrane potential, the repolarization of the action potential is followed by a slow depolarization from about −71 to −54 mV, the threshold required to initiate another action potential. This slow, spontaneous depolarization drives cardiac automaticity and is related to a specialized current (If ). In the case of AV nodal cells, the fast upstroke is carried predominantly by an inward Ca2+ current. Repolarization is caused by delayed activation of the K+ current. The balance of inward and outward currents determines the net “pacemaker” current and is finely regulated by both adrenergic and cholinergic neurotransmitters. In the presence of AV block or abnormal SA nodal function, AV junctional cells in the region of the proximal penetrating bundle usually assume the role of pacemaker at rates slower than that of the sinus node. In the absence of disease in the AV junction, the escape rhythm occurs with a frequency that is about 67% of the sinus rate.29

Artificial Electrical Stimulation of Cardiac Tissue Artificial lipid membranes in their pure form are electrical insulators. The myocyte cell membrane (sarcolemma) is much more complicated. Specialized protein molecules in the membrane allow it to be conductive.30,31 These proteins, either singly or in certain groupings, form channels that open and close for transport of specific ions through the membrane in response to particular stimuli. The channel proteins are the end stages of processes that provide both active and passive transport of ions and molecules through the membrane. When application of a pacemaker or defibrillator pulse produces a local electric field gradient, ion drift in the extracellular fluid at that site, as well as ion flow within the cell and within the membrane, are affected by the field. The field-induced ion drift cannot be uniform within and outside the cell because of the different drift properties of different ion types, different ion and protein concentrations within and without the cell, and the barrier impedance effect of connections between cells. The effect of the stimulus is to change the transmembrane voltage of nearby myocytes sufficiently so that depolarization begins in and spreads from these myocyte membranes. Propagation of the stimulus to nearby myocytes occurs because the local transmembrane depolarization changes the voltage gradient across adjacent membranes sufficiently to trigger depolarization of those membranes. To cause an action potential to spread throughout the whole heart, an electrical pulse must stimulate a minimum of approximately 50 closely coupled cardiac cells.5 The result is a self-regenerating action potential that progresses in a wavelike, relatively slow manner beyond the local effect of the pacemaker stimulus. Away from immediate vicinity of the electrode, transmission of depolarization and its velocity depend in part on the resistance and capacitance properties of the membrane, on the opening and closing of ion channels, and on ion flows through the sarcolemma. MYOCARDIAL CELL ELECTRICAL PROPERTIES A single Purkinje fiber typically has an internal resistance that is two to three times greater than that of blood. The specific membrane resistance of a Purkinje fiber is on the order of 104 ohms–square centimeter (Ω-cm2). The time constant of the surface membrane is on the order of 10 msec, and the membrane capacity is about 1 microfaraday (µF)/cm2. Gap junctions are intercellular channels that provide a



9

1  Cardiac Electrical Stimulation

Sinus node Atrial muscle AV node Common bundle Bundle branches Purkinje fibers Ventricular muscle R T

P

U

Q

S

Time (msec) 0 100 200 300 400 500 600 700 Figure 1-4  Action potentials from different cell types in the heart. Specialized pacemaker and conduction cell types have distinct action potential characteristics. Activation times for a normal heartbeat demonstrate the spread of activation throughout the whole heart. AV, Atrioventricular. (From Malmivuo J, Plonsey R: Bioelectromagnetism: principles and applications of bioelectric and biomagnetic fields. New York, 1995, Oxford University Press.)

SINGLE-CELL EXCITATION BY ELECTRICAL STIMULUS The basic principle underlying cardiac pacing is the ability of an externally applied voltage difference to generate a self-propagating wavefront of cardiac depolarization in the heart. This wavefront is the result of propagation of action potentials across the myocardium, a process that involves the opening and closing of ion channels in the membrane. In reality, an applied external electrical stimulus initiates cardiac excitation as a result of passive effects on the transmembrane potential. This is a result of a change in potential that is induced in the extracellular space. Because of the relatively high impedance between cells across the membrane and through the gap junctions compared with the lower impedance path through the extracellular space, relatively small amounts of current pass through the cell membrane. When an external stimulus is applied, the potential within the intracellular space does not vary appreciably over the length and width of a cardiac myocyte (Fig. 1-5). However, near the stimulating electrode, the extracellular stimulus causes a field gradient to develop in the extracellular space. The transmembrane voltage (Vm) is equal to the difference in potential inside the cell (Vi) minus the potential outside the cell in the extracellular space (Ve), so a change in extracellular potential with little change in intracellular potential across the length of the cell results in a net difference in Vm. This is represented as follows:

Vm = (Vi − Ve )

Thus, as considered along the length of a cardiac myocyte, one end has a more negative transmembrane potential than the other. This leads to a net hyperpolarization of the cell on one end and depolarization on the other end. The induced change in Vm has the capacity to open voltage-gated ion channels within the cardiac cell membrane. Voltagegated Na+ channels are opened by a decrease in Vm. If an external

Vi Vm+

Vm–

A

+

–

Ve Vm

Voltage

pathway for electrical communication between myocytes. Their diameter is about 2 nm and length about 12 nm. Gap conductance is voltage sensitive.32 Under pathologic conditions, such as severe hypoxia or ischemia, gap junctions will not function normally.

B

Vi Ve

Figure 1-5  Response of a cardiomyocyte to electric field. Relatively little current passes through the relatively high impedance cell membrane. A, Cardiomyocite exposed to extracellular electric field. The intracellular voltage (Vi) is relatively low impedance and thus does not vary from one side of the cell to the other while the extracellular voltage (Ve) drops from one end of the cell to the other. B, Transmembrane potential (Vm) is defined as Vm = Vi − Ve, so the left side of the cell is hyperpolarized by the external field while the right side of the cell is depolarized. If the extracellular field gradient is large enough, the rightsided portion of the cell may reach threshold and initiate an action potential that may activate the entire cell and spread to adjacent cells through gap junctions. (From Dosdall DJ, Fast VG, Ideker RE: Mechanisms of defibrillation. Annu Rev Biomed Eng. 12:233-258, 2010.)

10

SECTION 1  Basic Principles of Device Therapy

stimulus is strong enough to cause Vm on the depolarized side of the cell to rise above the threshold to activate the inward Na+ channels, the influx of Na+ ions rapidly leads to further depolarization of the cell and initiates an action potential. This action potential spreads to adjacent cells by passing ions through gap junctions and raising Vm in adjacent cells, and initiating an active response through the activation of Na+ channels. FACTORS DETERMINING CAPTURE BY AN ELECTRICAL STIMULUS In order for an electrical stimulus to stimulate (capture) myocardium, it must be applied with sufficient amplitude, for a sufficient duration (measured in milliseconds), at a time when the myocardium is electrically excitable. Many clinical factors determine whether a stimulus of given amplitude will result in capture, including proximity of the electrode to the myocardium, pathology of the underlying cardiac tissue, size and shape of the electrode, and effects of drugs and hormones, as well as electrolytes. For routine clinical practice, the most important factor is that the lead must be positioned close to well-functioning myocardium in a secure manner. (It is also important that the lead does not stimulate the diaphragm or the phrenic nerve, that it is at a site that results in good hemodynamic function, and that the location does not allow the electrode to bump other electrodes.) After adequate lead positioning, the strength-duration relation is the next most important consideration. CURRENT DENSITY, ELECTRIC FIELD GRADIENT, AND PROPAGATION OF DEPOLARIZATION There are two approaches to thinking about how an electrical stimulus induces a self-propagating wavefront of depolarization within myocardium. The current density approach considers the magnitude of current flowing through a given mass of myocardium between the stimulating electrodes and finds this to be the critical factor required to induce a regenerative wavefront of depolarization. From this point of view, the stimulation threshold is a function of current density (amperes/cm2) in the excitable myocardium underlying the electrode.33-36 The electric field approach holds that the critical factor affecting myocardial depolarization is the magnitude of the electric field gradient (volts/cm in viable tissue) that is induced in the myocardium beneath the stimulating electrode.37,38 These approaches are fundamentally the same in that there is a mathematical relationship between the electric field gradient and the current density at the stimulating electrode. Because reactance as well as resistance is present, Ohm’s law in this context must be stated in terms of impedance, as follows:

v = iz

[1-5a]

where v is the stimulus voltage, i is the current, and z is the impedance to current flow. Note that each of these is a vector. Also note that z varies with current density at the electrode (because of interface properties), with direction of current flow (anisotropy), and with domain (extracellular or intracellular). The total energy of the pacing stimulus is determined by the applied voltage, the current, and the duration of the stimulus, as follows:

t

J t = ∫ v t i t dt 0

[1-5b]

where Jt is the energy delivered (expressed in joules) from time zero to time t during the pulse, vt is the voltage, and it is the current at the electrode at instantaneous time t during the pulse. This equation indicates that the total energy delivered during the pulse is proportional to the area under a curve. The curve is formed in the vertical dimension by the instantaneous product of voltage and current applied to the electrode, and in the horizontal dimension by the time elapsing during the pulse. When the time t reaches the programmed pulse duration, the pulse ends. The area under the curve then represents the electrical energy transferred during the time span of the pulse. The equation can easily be solved in real time with a small digital computer, provided

that continuous phasic measurements of the voltage and current in the wire going to the electrode are available. (Note that this equation has blood flow and pressure energy analogs.39) For pacemakers in almost all clinical situations, it is more practical and very reasonable to calculate the energy delivered by a constantvoltage pulse through a pacemaker electrode by means of an approximation. The assumptions are that (1) the voltage during the pulse really is constant and (2) the current flowing is linearly related to the voltage. Because neither is quite true, the questions become (1) whether the information obtained proves useful and (2) to what degree it can be misleading. If the assumptions are close to being correct, the following equation can be approximately correct and useful: V V2 t= t, R R where J is the energy delivered, V is the “constant” voltage, I is the current, R is the resistance, and t is the stimulus duration. This equation indicates that the total energy delivered can be estimated by multiplying the voltage reading displayed on the pacing systems analyzer (PSA) by the current reading on the PSA and multiplying that product by the stimulus duration. Alternatively, the voltage reading can be squared, then divided by the resistance reading, and the quotient multiplied by the stimulus duration. The virtue in this calculation is that ordinary equipment can provide a quick, approximate determination of the total energy delivered per stimulus. In clinical practice, however, the usual range of good or acceptable values for pacing threshold current and voltage is known, and there is rarely a need to calculate the delivered energy. The stimulation threshold of isolated cardiac myocytes depends on their orientation within an electric field. The threshold is lowest when the myocytes are oriented parallel to the field and highest when the axis of the myocytes is perpendicular to the field.40 It is clear that myocardial stimulation may be induced with anodal or cathodal stimulation, or both, although with somewhat different characteristics. Various investigators have used several different parameters to express stimulation threshold, including current (mA), potential (V), energy (J), charge (Q), pulse width (t, msec), and voltage multiplied by stimulus duration (V-sec).41-47 For the purposes of this chapter, the myocardial stimulation threshold for pacing is defined as the minimum stimulus amplitude at any given pulse width required to consistently achieve myocardial depolarization outside the heart’s refractory period.48 Stimulation thresholds measured with a constant-voltage (CV) generator are stated in volts, and those of a constant-current (CI) generator are stated in milliamperes (mA). Note that a true constant-voltage generator may yield a slightly different stimulation threshold than the pseudoconstant-voltage generators in ordinary use. Why must an electrical pacing stimulus rely on propagation in myocardium rather than directly exciting the entire heart? With the magnitude of a stimulus generated by a pacemaker pulse generator, the electric field gradient and ion current density near the electrode are great enough to trigger an action potential only extremely close to the electrode. Unless propagation of the local depolarization occurs, no cardiac contraction will result. In contrast to cardiac pacing with direct production of only local depolarization and dependence on self-propagation of depolarization, defibrillation involves direct depolarization or hyperpolarization of a large portion of the heart. This is necessary to provide at least the minimum local voltage gradient required to produce depolarization over major portions of the myocardium. To do so requires a stimulus intensity that is much greater than that required for pacing49 (see Chapter 2 for a thorough discussion of defibrillation).

J = VIt = V

ELECTRIC POTENTIAL GRADIENTS AND CURRENTS FOR STIMULATION AND DEFIBRILLATION When the electric field exceeds approximately 1 V/cm in the extracellular space during diastole, myocardial stimulation (capture) results. The electric field must be achieved only in the area of several dozen



cells and may be achieved typically with less than 0.5 mA. When the electric field strength is increased to 6 V/cm, ventricular fibrillation may occur if the stimulus is applied during the vulnerable period (approximately the peak of the T wave). An area where the voltage gradient is at least 6 V/cm must be achieved at a distance of 1 cm from the electrode. To accomplish this, a current of approximately 20 mA is required to initiate ventricular fibrillation. This same field strength (6 V/cm) is also required to interrupt ventricular fibrillation (defibrillation). However, defibrillation requires the minimum field intensity to be approximately 6 V/cm at almost all points in the myocardium. In order to achieve this minimum electric field gradient at the same instant over the entire heart, a very large shock current, typically more than 10 A, must be applied. This current is thousands of times greater than the current required for pacing.49 When a pacemaker pulse is applied, electrically excitable myocytes respond with a wave of depolarization followed by repolarization in the myocardium. Depolarization of a small, local group of myocytes begins the self-propagating process. The initial depolarization adjacent to the electrode produces a potential gradient great enough at neighboring myocytes to result in their depolarization. The process is a self-regenerating mechanism that requires time to spread, and once established, it is largely independent of the distance from the stimulating electrode. Defibrillation is largely accomplished by providing an extremely large potential gradient between the defibrillation electrodes. This produces, at one instant within local myocardium everywhere in the heart, at least a 6 V/cm gradient. In contrast, pacing is accomplished by providing a gradient of approximately 1 V/cm or less at a local site and relies on self-propagation to spread the depolarization process throughout the myocardium. VIRTUAL ELECTRODE EFFECT Virtual electrodes are important because they can serve as sites that initiate or prevent depolarization of myocytes.50 Newton and Knisley51 defined virtual electrodes as “experimentally observed regions of large delta Vm that arise distant from the stimulating electrode.” “Delta Vm” (ΔVm) here represents the change in voltage difference across the myocyte membrane during application of the stimulation current. A virtual electrode can be described as a collection of charge predominately of one sign at a site away from a regular electrode. If, in an electrically neutral solution, ions of one charge sign are moved away by an electric field, a relative excess of ions of the other charge sign will be left or will move in the opposite direction. For example, if the regular electrode is paced with a negative-going stimulus, a site elsewhere in the tissue (i.e., not at this physical electrode) may become transiently positive and alter the transmembrane potentials of cells at that site.52-55 In cardiac tissue, a virtual electrode can occur as an effect of anisotropy after a defibrillation shock and can initiate refibrillation. A virtual electrode may also result from ion redistribution patterns in a nonanisotropic medium. In anisotropic tissue, charge redistribution produced by a physical electrode can have a “dog bone” shape.56 The virtual electrodes occur at sites where ions flow into or out of cells by crossing the cell membrane. An applied unipolar stimulation current flows into some cells while simultaneously flowing out of others, thus producing negative and positive virtual electrodes at different locations. In an anisotropic medium, a cathodal pulse produces a virtual electrode with a dog bone shape oriented perpendicular to cardiac fibers and containing a large ΔVm, and a pair of virtual electrodes containing negative ΔVm at locations along the fibers. Theoretical models have shown that this effect can be attributed to unequal tissue anisotropy in the intracellular and extracellular spaces; that is, intracellular current at a given location favors the longitudinal direction 10 to 1, whereas extracellular current favors the longitudinal direction only 3 to 1 (Knisley, personal communication, 2005). Knisley and Pollard57 studied the effects of electrode-myocardial separation on cardiac stimulation of rabbit hearts in conductive solution. The

1  Cardiac Electrical Stimulation

11

electrode-myocardial separation altered the spatial distribution of ΔVm and increased the pacing threshold. In regard to electrode-myocardial tissue separation, Shepard et al.,58 during 1980s transthoracic defibrillator implantation procedures, sewed the electrodes used for rate sensing onto the outer surface of the pericardium. Sensing voltages were normal. Pacing thresholds of these electrodes measured were high (3.7 ± 1.9 mA and 4.5 ± 2.19 V at 0.5msec stimulus duration), as would be expected both from current density considerations and from Knisley’s findings. The initial impedance was 1209 ± 383 Ω, and the chronic impedance was 1550 ± 358 Ω at a median follow-up time of 964 days. The thresholds had by then decreased to 3.8 ± 2.07 V and 2.7 ± 1.8 mA. The transpericardial distance from underlying myocardium did result in high initial pacing thresholds (and in the special distribution of ΔVm near the electrodes). However, the long-term tissue reaction of pericardium and underlying myocardium to the presence of these electrodes was not detrimental in terms of threshold evolution. Virtual electrodes normally exist near an electrode when a pacing pulse is applied. Nikolski and Sambelashvili,59 studying Langendorffperfused rabbit hearts, found that stimuli of magnitude five times threshold produced “make” or stimulus-onset excitation from virtual cathodes, whereas near-threshold stimuli produced “break” or stimulus-termination excitation from virtual anodes. In studying how cardiac tissue damage at an electrode results in a pacing threshold increase, Sambelashvili et al.60 found that the virtual electrode effect was destroyed by very strong (40 mA, 4 msec, biphasic, 240/min) pacing pulses applied for 5 minutes. Fluorescent optical mapping showed that decrease or loss of the virtual electrode polarization was associated with pacing threshold increase. Propidium iodide staining showed tissue damage within an area about 1 mm in diameter surrounding the electrode. Another view of the effect of strong stimuli as just described is that local tissue damage at a pacing electrode increases the distance from the electrode to normal myocytes. Because electric field strength and current density decrease with distance from the electrode, an increase in pacing stimulus amplitude applied to the electrode is necessary to restore the stimulus current density to the pacing threshold level of myocytes at the outer edge of the damaged tissue. ANODAL AND CATHODAL STIMULATION The polarity of a stimulus can be cathodal or anodal. In determining how an artificial electrical stimulus interacts with cardiac cells to initiate this self-propagating wavefront, the mechanism of excitation of cardiac tissue by an electrical stimulus depends on the polarity, strength, and duration of the stimulus. Cardiac excitation may occur immediately adjacent to the electrode by direct stimulation or at a distance from the electrode through virtual electrode effects. The two mechanisms by which electric current stimulates cardiac excitation close to electrodes are cathodal make and anodal break. Virtual electrodes cause cardiac excitation by cathodal break and anodal make phenomenon. Cathode make excitation occurs adjacent to a cathode from the high current density immediately surrounding the electrode. Current flows in the extracellular space and causes hyperpolarization and depolarization of opposite ends of the cell, as shown in Figure 1-5. Current also passes through the cell membrane and causes an increase in Vm that exceeds the threshold for fast Na+ channels to activate. Excitation spreads outward from the central excitation site in an elliptical shape because of tissue anisotropy (Fig. 1-6). Cathode make occurs on the rising edge of the stimulation pulse (Fig. 1-7, A). An anode tends to hyperpolarize cells immediately adjacent to the electrode, but virtual cathodes form on both sides of the central anode. Anode make excitation causes activation to spread on both sides of the central hyperpolarized region until the excitation merges into a single wavefront and spreads elliptically (Fig. 1-7, B). The threshold for stimulation with cathode make is typically higher than for anode make because the virtual cathodes that form at a distance from the central

12

SECTION 1  Basic Principles of Device Therapy

Cathodal make 0 – mV –100 Anodal break

0 + mV –100 Figure 1-6  Action potentials are initiated by cathodal and anodal excitation. Excitation make and break phenomena occur under and near electrodes. Cathodal make occurs when the excitation current directly excites the tissue under the electrode. Anodal break occurs under the excitation electrode on termination of the stimulating pulse. (From Antoni H: Electrical properties of the heart. In Reilly JP, editor: Applied bioelectricity: from electrical stimulation to electropathology. New York, 1998, Springer, p 160.)

0

3

6

anode are weaker and have less depolarizing power than the direct effects of a central cathode. Cathode break excitation occurs when the stimulating pulse is turned off (Fig. 1-7, C). While the stimulation pulse is turned on, the tissue under the stimulating electrode is depolarized, and the fast Na+ channels open and then become unexcitable. Propagation of the excitation is repressed somewhat by the virtual anodes on either side. On termination of the stimulating pulse, the virtual anodes disappear, and excitation spreads from the active tissue under the electrode to the hyperpolarized regions under the virtual anodes. Because the tissue under the virtual anodes was hyperpolarized, the Na+ channels are fully excitable, and the excitation wavefront spreads rapidly through the area previously covered by virtual anodes. Cathode make occurs at a lower threshold than cathode break and is not observed unless tissue is refractory when the stimulation pulse commences but becomes excitable during the pulse. If the tissue has recovered by the time the pulse turns off, cathode break may occur. If the tissue is unexcitable surrounding an anode at the beginning of a stimulation pulse, anode break excitation may result from a mechanism similar to that of cathode break. Excitation may be initiated by the termination of the excitation pulse (Fig. 1-7). Hyperpolarization directly below the anode causes the Na+ channels to become excitable. Depolarization from the virtual cathodes then rapidly propagates into the hyperpolarized region under the anode (Fig. 1-7, D). The virtual cathodes are relatively weak compared to the hyperpolarizing effect of the anode, but the activation spreads from the depolarized region into the hyperpolarized region because the cell membrane has a nonlinear response by which hyperpolarization decays more rapidly than does depolarization. Because anode break relies on virtual cathodes to initiate excitation in recently recovered tissue, however, this mechanism of excitation has the highest threshold of all, the make or break excitation mechanisms.

9

12

15

CM

A

AM

B

15 mV

–85 mV

CB

–185 mV

C

AB

D Figure 1-7  Computer simulation of four types of excitation with stimulating electrode (black rectangle). Cathode make (A), anode make (B), cathode break (C), and anode break (D) excitation are shown at various times; columns are time (t) in milliseconds. In A and B, t = 0 when the stimulation pulse turns on, and in C and D, t = 0 when the stimulation pulse is turned off. (From Wikswo JP, Roth BJ: Virtual electrode theory and pacing. In Efimov IR, Kroll MW, Tchou PJ, editors: Cardiac bioelectric therapy: mechanisms and practical implications. New York, 2009, Springer Science, pp 283-330.)



1  Cardiac Electrical Stimulation

Anode and cathode make and break phenomenon have been detected in computer models and verified in animal experiments.54,61 Optical mapping techniques with voltage-sensitive dye have been particularly useful in illuminating these mechanisms of stimulation.

Strength-Duration Relationships CHRONAXIE, RHEOBASE, ENERGY, AND PULSE DURATION THRESHOLDS





Irh

I=

[1-5c]

−t

threshold in terms of pulse duration can be misleading if the stimulus amplitude setting is omitted or unknown. In 1892, Hoorweg66 used a voltage source, a galvanometer, and lowleakage capacitors to conduct quantitative stimulation studies. He found that the voltage at which a capacitor must be charged to cause depolarization of nerves and muscles is an inverse function of the capacitance of the capacitor, as follows: Vc = aR + b / c



The intensity of an electrical stimulus (measured in volts or milliamperes) that is required to capture the atrial or ventricular myocardium depends on the duration of the stimulus.62,63 The historical background and the relations between the various electrical factors have been reviewed, further studied, and clearly stated by Blair,64 and by Geddes65 for electrode-electrolyte interface function and models. The interaction of stimulus amplitude and stimulus duration (pulse width) defines the strength-duration curve (Fig. 1-8). Lapique described this exponential relationship of stimulus intensity (current), I, and pulse duration, t, as follows:

1− e τ

where Irh is the rheobase current, e is the mathematical constant 2.718, and τ is the membrane time constant. The voltage or current amplitude required for endocardial stimulation has an exponential relation to the pulse duration, with a relatively flat curve at durations of longer than 1 msec and a rapidly rising curve at durations of less than 0.25 msec. Because of this fundamental property, a stimulus of short pulse duration must be of much greater intensity to capture the myocardium than a longer-duration pulse. Conversely, increasing the pulse width to longer than 1 msec has minimal influence on the intensity of the stimulus that is required for capture. Therefore, if one defines the stimulation threshold in terms of pulse amplitude without also specifying the pulse duration, important information is neglected. Similarly, specifying the capture

Threshold (V, µJ, µC)

x

Energy

4 x x

3

x x

x

x

x

x

x

Charge

x

2 Potential

Rheobase

1 Chronaxie 0 0

.2

.4

.6

.8

1.0

1.5

Pulse width (msec) Figure 1-8  Relationships between chronic ventricular canine constantvoltage strength-duration curves expressed in terms of potential ( V ), charge (µC), and energy (µJ) for a tined unipolar lead with an 8-mm2, polished, ring-tip electrode. Thresholds are measured at the point of gain of capture. Rheobase is the current or voltage threshold to the right that is independent of pulse width. Chronaxie is the pulse width at twice the rheobase. (From Stokes K, Bornzin G: The electrodebiointerface [stimulation]. In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, Futura, 1985, pp 33-78.)

[1-6]

In this experimentally determined equation, Vc is the threshold voltage to which a capacitor of capacitance C must be charged to produce stimulation on discharge. R is the resistance of the circuit through which the capacitor is discharged, and a and b are coefficients that vary with the specimen (tissue) tested. Here, the experimentally determined constant a has the dimension amperes and the constant b has the dimension ampere-seconds. (The capacitance can be derived from the equation

C=

Q V

where C is the capacitance, Q is the charge on either conductor, and V is the magnitude of the potential difference across the capacitor; the capacitance has the dimension ampere-seconds [or coulombs] per volt; 1 coulomb per volt = 1 farad). Hoorweg determined that there was only one specific capacitance value for which the threshold charge was a minimum. He also determined that the threshold charge was a linear function of the stimulus duration, “intersecting the y-axis above zero.” However, Hoorweg did not have the capability to measure thresholds at very short pulse durations. In reality, the threshold charge increases toward infinity as the pulse duration approaches zero. In 1901, Weiss67 reported that the threshold charge required for stimulation increases linearly with stimulus duration. He called this relationship the “formule fondamentale.” If I represents the magnitude of the current, t is the stimulus duration, and a and b are constants determined by analyzing the data, Weiss found that: t

t

5

13

∫ Idt = at + b 0

[1-7]

Or, because ∫ idt = Q, the charge in the capacitor at threshold stimu0 lus duration t, Q = at + b. For a constant-current stimulus, this can be stated in words as threshold charge requirement = a amperes times t seconds + b, where b is a constant with dimensional units of ampereseconds. The values of the constants a and b vary with the tissue tested. The left-hand side of Equation 1-7 indicates that the charge delivered into the electrode is, for a constant current, the magnitude of the current multiplied by the duration of the current. The right-hand side states that the charge required to stimulate at threshold is a minimum of b ampere-seconds plus the product of the current level a and the stimulus duration t. Weiss67 noted that, for various stimulus durations tested, the quantity of charge required to initiate depolarization remained constant. The statement that the threshold charge requirement does not change with stimulus duration is true only within a limited range. The limitation leads to the concept of rheobase, as stated in 1909 by Lapique;68 when pulse duration is increased beyond a limited range, the current requirement does not decrease further. The charge delivered continues to increase as pulse duration is increased. Lapique called this minimum current the rheobase, or the lowest stimulus current that continues to capture the heart when the stimulus duration is made extremely long. In this situation, further increases in stimulus duration no longer reduce the magnitude of current required to stimulate the heart. Note from Equation 1-7 that the ratio a/b has the dimensions/ amperes divided by (ampere-seconds); this expression reduces in dimensions to the reciprocal of the stimulus duration. Lapique called the time seen in the a/b ratio the chronaxie, specified in seconds. Chronaxie time experimentally turns out to be approximately the threshold pulse duration at twice rheobase amplitude, and it has become defined

SECTION 1  Basic Principles of Device Therapy

as such; this is illustrated in Figure 1-8. Note again that rheobase is specified in terms of current, and chronaxie is specified in terms of time. Lapique69 determined that stimulation at the chronaxie pulse width approaches the minimum threshold energy. Therefore, the two most important reference points on a current or voltage strength-duration curve are rheobase and chronaxie. Obtaining a true rheobase typically requires pulse widths of 10 msec or greater. For clinical purposes, rheobase can be approximately measured at pulse widths of 1.5 to 2 msec. The value obtained may be slightly greater than the true rheobase. Therefore, the chronaxie stimulus duration obtained by setting the stimulus current at twice the approximate rheobase current and then finding the minimum stimulus duration that will result in capture is slightly low. In a time-saving, useful, and reasonable clinical sense, one may empirically set the stimulus duration at a value determined from experience, such as 0.4 to 0.5 msec and then determine the current and voltage thresholds. Safety factor allowances of current and voltage are then added or subtracted based on the patient’s current and projected clinical status (see later discussion). The goal is to find the combination of pacing threshold stimulus current, voltage, and pulse width that results in minimal charge drain from the pulse generator battery at normal pulse rates. Figure 1-8 shows that, for capture to be accomplished, the least charge was required at the shortest pulse duration (0.1 msec in the figure), but the least energy was required at about 0.3-msec stimulus duration. A very short pulse duration puts thresholds close to the steeply ascending limb of the voltage or current curve, where slight fluctuations can risk loss of capture. For this reason, Irnich70,71 recommended that chronaxie, or the pulse duration slightly to the left of chronaxie, is the most efficient pulse duration for both pacing and defibrillation. In most cases, the pulse duration at chronaxie or slightly greater appears to represent the best overall compromise between adequate safety and generator longevity. One also considers the expected stability or instability of the patient’s status, patient compliance, and follow-up arrangements, both short and long term. Pacing thresholds can also be specified in terms of only energy (microjoules, µJ) or only pulse duration (milliseconds). However, reliance on specifications in either of these units alone can be misleading. Doing so discounts that, regardless of the pulse duration or energy used, the heart cannot be stimulated unless the stimulus amplitude exceeds the rheobase current.72 For example, if rheobase is achieved with a pulse amplitude of 0.5 V and 10 msec, the pulse at this point on the strength-duration curve will have 5 µJ of energy (current × voltage × time) with a 500-Ω lead (1 mA × 0.5 V × 10 msec = 5 µJ). A 0.4-V, 20-msec pulse on a 500-Ω lead has 6.4 µJ of energy (28% greater than the “threshold” energy at 10 msec) but will not result in cardiac capture. Increasing the pulse duration to 100 msec at 0.4 V results in 32 µJ of energy (540% greater than “threshold” energy at 10 msec) but will still not capture the heart, for the same reason. No matter how far the pulse duration is extended (with increased energy), the myocardium will not be captured unless the stimulus amplitude is at least as great as the rheobase value. Therefore, calculation of the energy threshold at very long pulse durations does not provide clinically useful information.73 Coates and Thwaites74 studied the strength-duration curve in 229 patients with 325 leads. The mean atrial chronaxie (n = 101) was 0.24 ± 0.07 msec, and the mean ventricular chronaxie (n = 224) was 0.25 ± 0.07 msec. Mean atrial and ventricular rheobase values were 0.51 ± 0.2 V and 0.35 ± 0.14 V, respectively. Because the pulse generators were set at factory-nominal pulse durations of 0.45 to 0.50 msec, the authors concluded that pacing was suboptimal from the efficiency point of view. They pointed out that battery drain would be reduced by programming pulse duration to the chronaxie value and then programming the voltage to double the chronaxie value. In a study of excitability of rat atria during postnatal development up to 120 days, Gurjao de Godoy et al.75 found that atrial rheobase decreased with animal age and was altered by electric field orientation. Atrial chronaxie increased only with age. The clinician might keep in mind that the chronaxie is influenced not only by electrode material, size, and

stimulation mode, but also by clinically varying biochemical factors. Certainly, marked variations in pacing threshold, either up or down, do occur months and years after implantation in some children and adults.76 As stated earlier, on the left side of the chronaxie point of the strengthduration curve, the current and voltage rise rapidly as stimulus duration decreases. At pulse durations greater than chronaxie, the slope of the strength-duration curve gradually flattens. Small changes in stimulus amplitude are then less likely to result in loss of capture, especially if the threshold has increased because of a pathophysiologic condition. This increased safety comes at the cost of decreased battery life. PRACTICAL APPLICATION TO THRESHOLD MEASUREMENT To determine the strength-duration relationship, the clinician must measure the stimulation threshold at specific amplitudes and pulse durations. However, the result obtained varies somewhat with the method used. Usually the threshold, as measured at a specific stimulus duration (e.g., 0.5 msec), will be slightly higher when the stimulus amplitude is gradually being increased than being decreased. The threshold can also be measured by holding the output voltage constant and changing the stimulus duration. The stimulation threshold then is defined as the lowest-amplitude pulse duration that results in consistent capture of the myocardium. Only the threshold measured in this way can be clinically useful, as noted earlier. It also can be deceptive, because the strength-duration curve is not linear. For example, if the pulse duration threshold is 0.5 msec at an amplitude of 2 V, reprogramming the pacemaker stimulus to a pulse duration of 1 or even 1.5 msec would provide a very small margin of safety 10 9 8

Volts

14

7

D

6

2×V E

5 4

C

3 2

A

2×V 2 × PW

B

1 0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 2.0

Pulse duration (msec) Figure 1-9  Programming of pulse amplitude and pulse duration based on analysis of the strength-duration curve in a patient evaluated at the time of pulse generator replacement (6 years after lead implantation). The rheobase voltage was 1.4 V, and the chronaxie pulse width (PW) was 0.30 msec. Note that the stimulation threshold, determined by decreasing the stimulus amplitude at a constant pulse duration of 0.5 msec, was about 2 V (point A). Doubling of the PW on the relatively flat portion of the strength-duration curve (point B) provides little safety margin for ventricular capture. In contrast, consider a threshold value on the steeply ascending portion of the strength-duration curve (point C). Doubling of the pulse amplitude doubles the safety margin on this portion of the curve, but it lies very close to the curve (point D). An appropriate setting for the chronic pacing pulse might be achieved by doubling the pulse amplitude from point A to point E. Also note that a similar programmed setting would have been obtained had the pulse duration been tripled from point C. Thus, the shape of the strengthduration curve has an important influence on the choice of the amplitude and duration of the pacing pulse.



1  Cardiac Electrical Stimulation 1.0

Effect of Pacing Rate on Stimulation Threshold

0.8 0.7 0.6 0.5

Increment

0.4

Decrement

0.3 0.2 0.1 0.0 2250 2000 1750 1500 1250 1000

750

500

250

Cycle length (msec) Figure 1-10  Pacing thresholds determined by gradually incrementing and decrementing the pulse amplitude until gain and loss of capture, respectively, are demonstrated in a patient with complete atrioventricular block. The pacing threshold was determined at cycle lengths of 2000, 1500, 1000, 750, and 500 msec and with a constant pulse duration of 2.0 msec. To prevent variation in cycle length during incrementing and decrementing pulse amplitudes, a backup pulse was delivered at 25 msec. Note that the threshold values determined in this manner, with increments and decrements of the stimulus amplitude, are similar. Therefore, the Wedensky effect may be marginal when the pacing cycle length is maintained at a constant value.

(Fig. 1-9). Instead, doubling the stimulus amplitude to 4 V at a pulse duration of 0.5 msec would provide an adequate margin of safety. In contrast, consider that, in this same patient, the pulse duration threshold is 0.15 msec at a pulse amplitude of 3.5 V. Increasing the pulse width to 0.45 msec would also provide an adequate safety margin. The reason that a threefold increase in pulse width is not adequate in the first example but is acceptable in the second relates to the location of the threshold stimulus on the strength-duration curve. Consideration of programming the pulse generator to twice the voltage threshold found at the chronaxie pulse duration is only a starting point. Determination of the safety margin necessary for any particular patient depends on several physiologic factors, as discussed next. Capture Hysteresis (Wedensky Effect) The threshold stimulus amplitude measured by decreasing the voltage or current until loss of capture occurs is sometimes less than that determined by increasing the stimulus intensity from below threshold until gain of capture occurs. This hysteresis-like phenomenon is the Wedensky effect,77 the effect of subthreshold stimulation on the subsequent suprathreshold stimulation when the stimulus amplitude is being increased (Fig. 1-10). Langberg et al.78 observed no demonstrable capture hysteresis at pacing cycles longer than 400 msec. They concluded that the Wedensky effect was related to asynchronous pacing in the relative refractory period when incrementing the stimulus intensity, versus the synchronous late-diastolic stimulation when decrementing the stimulus amplitude until loss of capture. Swerdlow et al.79 showed in a study of 40 patients that cardiovascular collapse occurs at AC current levels less than the ventricular fibrillation current threshold. The continuous capture threshold for AC current is less than the capture threshold for a single ordinary pacing stimulus. The authors suggested that continuous capture at low levels of AC current requires a cumulative effect of subthreshold stimuli; this is a variation of the Wedensky effect. The safety standard for 60-hertz (Hz) current leakage longer than 5 seconds should be 20 microamperes (µA) or less to avoid intermittent capture.

Hook et al.80 reported a significant increase in ventricular pacing threshold in 10 of 16 patients at 400 msec and in 15 of 16 at 300 msec (relative to a pacing cycle length of 600 msec). The phenomenon was not observed at every trial (e.g., 12 of 72 trials at 400 msec). The patients were all candidates for ICDs, and 9 of 12 were receiving antiarrhythmic drugs. The leads were bipolar: a pair of epicardial corkscrews in 11 patients and endocardial screw-in lead in five patients. The atrial stimulation threshold has also been shown to vary as a function of pacing rate.81,82 Katsumoto et al.83 reported that 29 of 36 patients exhibited constant-current atrial pacing threshold energy and current variations as a function of pacing rate in the range of 60 to 120 beats per minute (bpm). The pacing was done with activated vitreous carbon electrodes. Kay et al.84 found significant human atrial threshold changes as a function of pacing rate (125-300 bpm) using constant-voltage stimulation. They found a significant increase in rheobase voltage (Fig. 1-11), chronaxie, and minimum threshold energy at pacing rates greater than 225 bpm using platinized (low-polarizing) unipolar electrodes. They also determined strength-interval curves and found no correlation between atrial effective refractory period and rheobase voltage, chronaxie, or rate-dependent changes in either of these values. They concluded that the phenomenon is probably related to the “opposing effects of decreasing cycle length on the action potential duration and the slope of the strength-interval curve. Thus, if the pacing interval shortens to a greater extent than the refractory period and pacing stimuli are delivered during the ascending limb of the strength-interval curve (the relative refractory period), the diastolic threshold will increase.”84 The increase in stimulation threshold with increasing stimulation rate probably has minimal implications for bradycardia pacing. It is important for antitachycardia pacing, however, because threshold must be measured at rates required to interrupt the arrhythmia. In addition, the safety factors used with antitachycardia pacemakers must be based on thresholds measured at the clinically appropriate rates, rather than during pacing at resting rates.

Strength-Interval Relationships Voltage and current stimulation thresholds vary as a function of the coupling interval of the stimulus to prior beats and to the stimulation frequency used for the basic drive train. Figure 1-12 shows a typical ventricular constant-current strength-interval curve. At relatively long extrastimulus coupling intervals (>270 msec), the intensity of the extrastimulus required for ventricular capture is relatively constant, approaching the rheobase value. At shorter extrastimulus coupling 4 Atrial pacing rheobase (V)

0.9

Rheobase (V)

15

3 2 1 0 125

150

175

200

225

250

275

300

Pacing rate (beats per min) Figure 1-11  Effect of pacing rate on atrial rheobase voltage in patients. The rheobase voltage increases significantly for pacing rates greater than 225 beats/min (values shown as mean ± SEM). (From Kay GN, Mulholland DH, Epstein AE, Plumb VJ: Effect of pacing rate on human atrial strength-duration curves. J Am Coll Cardiol 15:1618-1623, 1990.)

16

SECTION 1  Basic Principles of Device Therapy

9 8 7 Current (mA)

6 5

Distal unipolar cathodal

4

Bipolar

3

Proximal unipolar anodal

2 1 0

Because the purpose of a pacing stimulus is to produce high current density at the electrode-electrolyte interface in the heart, the ideal situation is to deliver a low current from a very small surface area of electrode. If high current density (current magnitude divided by the plane area of the myocardium touched by the electrode) can be obtained with a small, high-impedance electrode, the current drained from the battery will be less than with lower impedance. At pacing threshold, a certain current density exists. If the interface area is made smaller, the current can be reduced equivalently and the same current density maintained. Minimizing the current needed for stimulation requires an optimal combination of interface area, current density, surface material and structure of the electrode, and increased impedance from making the electrode interface area smaller. An increase in impedance made to reduce current drain from the battery should be accomplished by making changes in the electrode, not by increasing the resistance of the wires to and from the pacemaker. Opposition to Stimulus Current Flow

240

280

320

360

400

Delay (msec) Figure 1-12  Strength-interval curves. Unipolar distal cathodal, unipolar proximal anodal, and bipolar strength-interval curves during an acute study in a patient with a temporary bipolar lead (equal-sized cathode and anode). The bipolar and unipolar anodal refractory periods are equal and are shorter than the unipolar cathodal refractory period. (From Mehra R, Furman S: Comparison of cathodal, anodal, and bipolar strength-interval curves with temporary and permanent pacing electrodes. Br Heart J 41:468, 1979.)

intervals (0.5

32

SECTION 1  Basic Principles of Device Therapy

titanium has been coated with platinized platinum or vitreous carbon. Others accept the concept that the oxide layer acts as the dielectric of a capacitor, so that no charge is transferred across the dielectric during stimulation. In that situation, current continues to enter and leave each side of the capacitor (see earlier discussion of Helmholtz capacitance). In any case, titanium oxide electrodes are highly corrosion resistant, and these combinations have been found to have excellent long-term performance as pacing electrodes.190-194 Some theories have held that the foreign body reaction is a response to the electrode material.195,196 As a result, many attempts have been made to improve thresholds through the use of more biocompatible materials. For example, some claim that pyrolytic carbons are more biocompatible and produce lower chronic thresholds than platinum.94,197-199 Besides having a different composition, these electrodes are also microporous. When similar electrodes are polished, we have found that the chronic canine thresholds are not significantly different from those observed with polished platinum electrodes. Proper electrode material selection certainly is necessary to prevent unacceptable toxic responses or corrosion. At this point, however, apparently no biocompatible electrode composition significantly improves thresholds. Not all conductive materials are suitable for use as electrodes. Certain materials, such as zinc, copper, mercury, nickel, and lead, are associated with toxic reactions in the myocardium and are unsuitable for use in permanent pacing leads.182 Stainless steel materials are highly varying in composition and microstructure, with great variation between production lots. Electrodes made from one lot may be acceptable, whereas those made from another lot may corrode unacceptably. Because some of the corrosion products may be inflammatory or toxic, high thresholds occasionally occur with these materials. Therefore, stainless steel materials are no longer used for implantable electrodes. The polarity of the electrode may also have an important influence on its chemical stability. For example, Elgiloy, a non-noble and highly polarizing metal alloy, was used in the past as a cathode. It could not be used as an anode because it is susceptible to significant corrosion. Although Elgiloy had other excellent qualities, it is no longer used as a pacemaker electrode. The materials presently used for permanent pacing electrodes include platinum-iridium, titanium (oxide), platinum- or carboncoated titanium, platinized platinum, vitreous carbon, and iridium oxide. The platinized platinum, “activated” carbon, and iridium oxide electrodes are associated with a reduced degree of polarization. A negligible degree of corrosion occurs with these materials. The vitreous carbon electrodes have been improved by roughening the surface, a process known as activation that increases the surface area of the interface, thereby reducing polarization. Fractal coating of the distal electrode also has been introduced as a method for reducing electrode polarization. This technique involves coating the distal electrode with a microscopic granular structure that produces a complex surface. Electrode Location (Epicardial, Endocardial, Intramyocardial) As shown previously in canine ventricles for electrodes without steroid elution, the type of fixation (as opposed to the location of the electrode) has no effect on stimulation thresholds, in that epicardially applied corkscrews, transvenous corkscrews, and passively fixed endocardial electrodes all tend to have about the same chronic thresholds. Most epicardial or myocardial pacing leads are used in pediatric patients, in whom threshold complications are relatively common.200,201 It is generally perceived that epicardial and myocardial electrodes without steroid elution have less desirable threshold performance than endocardial leads. One reason that the performance of epicardial and myocardial leads has lagged behind that of endocardial passively fixed leads is the mechanical limitations involved. Epicardial and transvenous active-fixation leads are significantly more complex and are more difficult to design with all the attributes necessary for low, chronic stimulation thresholds. Nonetheless, there is no inherent reason that transvenous active-fixation or myocardial electrodes should not perform as well as or better than endocardial systems.

The first transvenous steroid-eluting active-fixation lead, the Medtronic Model 5078 (Medtronic, Minneapolis), was bipolar, with an electrically inactive, fixed helix surrounding a 5.8-mm2 porous, platinized cathode. This lead had excellent electrical performance in both the atrium and the ventricle.202-205 However, difficulties with helix distortion and entrapment in some cases resulted in the abandonment of the design. Active-fixation steroid-eluting leads provide significantly reduced pacing thresholds compared with standard active-fixation leads. Active-fixation electrode thresholds tend to be slightly higher than those of passive-fixation steroid-eluting electrodes.206 Steroid elution has also been applied to epicardial leads; with a significant reduction in long-term pacing threshold compared with steroid-free leads.207 PHARMACOLOGIC EFFECTS ON CARDIAC STIMULATION Several types of antiarrhythmic drugs have been demonstrated to increase stimulation thresholds in both humans and animals. Type 1 drugs decrease Na+ conductance and decrease the rate of rise of the action potential. Therefore, it should be no surprise that these agents can increase the threshold for pacing. Type 1A drugs, such as quinidine208 and procainamide,209 may result in increased thresholds, especially when administered in high doses.210 Type 1C drugs, such as encainide, flecainide, and propafenone, have been associated with increased pacing thresholds.211-215 The increase in stimulation threshold with these drugs has been demonstrated to correlate with the change in QRS duration. In addition to the type 1 agents, propranolol has been shown to result in an increase in pacing threshold when administered intravenously.216 Amiodarone, lidocaine, tocainide, and verapamil reportedly have minimal effects on pacing threshold, although we have seen one patient with congenital heart disease in whom amiodarone reproducibly increased the pacing threshold to the point of exit block.217 METABOLIC EFFECTS ON CARDIAC STIMULATION Stimulation Thresholds Stimulation thresholds may rise during sleeping or eating, factors associated with withdrawal of sympathetic tone and increased vagal tone.218,219 In contrast, factors associated with increased sympathetic tone, such as exercise or assumption of the upright posture, are associated with a decrease in threshold. The myocardial stimulation threshold is increased by several metabolic abnormalities, including hypoxemia, hypercarbia, metabolic alkalosis, and metabolic acidosis. In the presence of respiratory or cardiac arrest, the pacing threshold may increase by well over 100%, resulting in loss of capture despite the use of a conventional safety margin. Because of this observation, antitachycardia pacing devices, such as pacemakers and ICDs, are often designed to deliver high-intensity stimuli during anti-tachycardia pacing or after a high-energy shock. In patients undergoing implantation of an ICD, Khastgir et al.220 were unable to demonstrate an increase in pacing threshold 10 and 60 seconds after defibrillation. Ventricular fibrillation was electrically induced, however, and defibrillation was promptly performed under controlled circumstances in this study. PHYSIOLOGIC AND PHARMACOLOGIC EFFECTS ON PACING In the presence of a primary respiratory arrest, pacing stimuli may not capture the myocardium until adequate ventilation and pH balance are restored. Therefore, careful attention to respiration and pH must be maintained during anesthesia in patients with implanted pacemakers to ensure continued myocardial capture. Ischemia produces variable effects on stimulation threshold, depending on the location of the pacing electrode relative to the ischemic myocardium. In the presence of acute myocardial ischemia, the resting membrane potential decreases



1  Cardiac Electrical Stimulation

(cells become partially depolarized), the action potential upstroke velocity decreases, and the action potential duration dramatically shortens. In the presence of metabolic blockade with 2,4-dinitrophenol, Delmar221 noted an upward shift in the strength-duration curve, indicating an increase in the current required for capture at all pulse durations. Therefore, if the stimulating electrode is located in an ischemic region, the stimulation threshold would be expected to increase. With further ischemia and infarction, the myocardial threshold may rise dramatically. This may be seen clinically in patients who develop an acute inferior myocardial infarction (MI) with right ventricular (RV) infarction; in such patients, a previously implanted pacemaker may suddenly lose capture. However, if the stimulating electrode is located in a nonischemic region (e.g., right ventricle), activation of the sympathetic nervous system may reduce the pacing threshold. Hyperkalemia has been shown to increase the stimulation threshold when the serum K+ concentration exceeds 7 mEq/L.222,223 In contrast, in the presence of hypokalemia, intravenous (IV) K+ may decrease the pacing threshold and restore capture of a subthreshold pulse.224 In addition, the reduced excitability during hyperkalemia can be corrected by IV calcium.225 Hyperglycemia in the range of 600 mg/dL may increase stimulation thresholds by as much as 60%.226 Therefore, patients who have diabetes or renal failure—conditions associated with the potential for altered glucose metabolism and electrolyte abnormalities—may need a larger safety margin than other patients. Hypothyroidism has also been demonstrated to increase pacing thresholds, an effect that is reversible with thyroxine replacement.227,228 As stated previously, glucocorticosteroids decrease stimulation thresholds and have been used to treat exit block both acutely and chronically.229 Endogenous and synthetic catecholamines are effective in lowering pacing thresholds.230,231 The effect of IV epinephrine or isoproterenol is to decrease the stimulation threshold initially, followed by an increase. IV or sublingual isoproterenol has been demonstrated to reverse high pacing thresholds related to antiarrhythmic drug toxicity.232

Biventricular Pacing Optimal clinical outcomes with permanent pacing require that the hemodynamic effects of the pacing site and the timing of atrial and ventricular contraction be carefully considered. As a result, cardiac resynchronization pacemakers and ICDs typically use electrodes in the coronary venous system to allow left ventricular (LV) stimulation. Implantation of permanent pacing leads in the cardiac veins is the predominant method for chronic LV stimulation.233 Although epicardial LV pacing using standard myocardial leads remains an effective method for biventricular pacing for the treatment of congestive heart failure, it requires a more extensive operation than a transvenous approach. Transvenous stimulation of the left ventricle requires placement of the lead into a branch of the cardiac venous circulation, usually a posterolateral vein. The electrical properties of chronic stimulation of both the right and left ventricles are complex. The com­ plexity of dual ventricular stimulation has been reported in canine studies.234 The initial clinical approach to cardiac resynchronization therapy (CRT) involved the use of a pulse generator with an atrial output circuit and a single ventricular output circuit. Thus, a pacing stimulus could be delivered in a series configuration to the right ventricle as the anode and the left ventricle as the cathode (or vice versa). Such a configuration had the advantage of having very high impedance because both the anode and the cathode were small, tip electrodes of the RV and LV leads. This approach was limited by the inability to time RV and LV stimuli separately and the marked prolongation of the intracardiac electrogram, which resulted from recording both RV and LV activation during sensing. Such a configuration was not acceptable for ICDs because oversensing of both RV and LV activation occurred in the combined electrogram. The next configuration used clinically involved splitting the current between the RV and the LV electrodes in a shared-cathodal

33

configuration. This configuration was limited by reduced current density at both the RV and the LV tip electrode resulting from the parallel circuit design and inability to separate timing of RV and LV stimulation. In addition, the ventricular electrogram was a composite of RV and LV activation, leading to double counting when the interventricular conduction time was prolonged. Pacing impedance in the ventricular split, bipole configuration was much higher than for either electrode alone. The anode was programmable to be either the pulse generator casing (unipolar split-cathodal configuration) or the ring electrode on the RV lead (bipolar split-cathodal configuration). The magnitude of the current flowing to either ventricular electrode was determined by the impedance of the two leads. The apparent pacing threshold in the left ventricle was dramatically affected by this splitcathodal configuration. For example, Mayhew et al.125 found that, when the unipolar LV (coronary venous) threshold was measured using the coronary venous tip electrode as the cathode and the pulse generator casing as the anode, the mean threshold was 0.7 ± 0.5 V at 0.5-msec pulse duration. Splitting the cathode between the LV tip and the RV tip electrodes increased the apparent LV threshold to 1.0 ± 0.8 V. When the anode was changed from the pulse generator casing to the RV ring electrode, the apparent LV threshold further increased to 1.3 ± 0.9 V. Therefore, a split-cathodal configuration greatly increased the apparent pacing threshold, compared with pacing the coronary venous lead alone. A further observation with the split-cathodal pacing configuration is that the impedance measured with a PSA does not behave as predicted by the simple application of Ohm’s law. For example, when the bipolar pacing configuration was used with the RV ring electrode as the anode,125 the pacing impedance was measured to be 705 Ω in the right ventricle and 874 Ω in the left ventricle. Using a split-cathodal bipolar configuration, the measured impedance was 516 Ω, higher than would be predicted by Ohm’s law, with both ventricles stimulated in parallel (390 Ω). The higher-than-predicted impedance is explained by the size and shape of the combined cathodes being different from those for either electrode alone. The combined-cathodal configuration results in a Warburg resistance and capacitance. Combining electrodes of similar size essentially doubles the cathodal surface area. Because the electrode resistance of a hemispherical electrode is about proportional to the square root of the electrode surface area, doubling the size of the cathode by combining the RV and LV electrodes decreases the Warburg resistance by a factor of 1/ 2. This helps to explain why the measured impedance using a split-cathodal configuration is not halved, as would be predicted by doubling the size of electrodes joined in parallel. Combining electrodes in parallel also increases the voltage droop during a constant-voltage pulse. Coronary venous pacing leads tend to result in higher impedance compared with endocardial RV leads (based on a lower volume of blood surrounding the electrode), and this further tends to shunt current from the higher-impedance electrode to the lower-impedance electrode when both ventricles are stimulated in parallel. This factor serves to increase the apparent LV threshold with the split-cathodal configuration. Current CRT devices use separate RV and LV output circuits, with multiple options for programming the stimulation vector. Thus, the left ventricle can be stimulated by a single electrode in the cardiac venous system or in the bipolar configuration with two electrodes in the cardiac veins. In addition, the unipolar configuration can be used with a single electrode in the cardiac venous system and the oppositepolarity electrode being the RV ring, the pulse generator casing, or another, more proximal electrode of a quadripolar LV lead. The polarities of the LV electrodes can also be reversed. With these multiple options for pacing the left ventricle, the undesirable effects of the older, split-cathodal pacing configuration have been overcome in newer CRT devices. However, because of the additional output circuit, there is additional battery drain with these newer devices. Another feature of CRT devices involves the use of bipolar or even quadripolar cardiac venous leads. These leads differ from traditional right atrial or RV leads in that the surface area of the two cardiac venous electrodes is often similar. Therefore, when the leads are

34

SECTION 1  Basic Principles of Device Therapy

programmed to the bipolar pacing configuration, the impedance is much higher than with unipolar pacing, because current flows between two small electrodes rather than between one small and one large electrode. In addition, the bipolar pacing threshold (measured in volts) is often considerably higher than the unipolar configuration, because the current delivered with higher impedance is reduced. The important clinical advantage of multiple electrode LV pacing leads and independent output circuits with programmable polarity options is the much better chance of finding a cardiac venous site that offers a low stimulation threshold while minimizing the chances of phrenic nerve stimulation.

Automated Capture Features To ensure ventricular capture and allow programming of a low margin of safety, newer pacemakers use algorithms that automatically detect ventricular capture. Based on the measured stimulation threshold, the amplitude of the pacing stimulus is automatically adjusted to provide a programmed margin of safety. The Autocapture feature of St. Jude Medical (St. Paul, Minn.) pacemakers automatically adjusts the amplitude of the stimulation pulse by detecting capture in the ventricle from the evoked ventricular electrogram (the evoked response). The St. Jude pacemakers may use either a bipolar or a unipolar ventricular pacing lead with low polarization properties for the distal electrode. The presence or absence of ventricular capture is determined by sensing of the evoked response from the tip electrode. These devices automatically determine the evoked response gain and sensitivity levels by delivering five paired ventricular pulses of 4.5 V at a minimum pulse duration of 0.5 msec or the programmed value. The first of the paired pulses measures the evoked response, and the second pulse is delivered within 100 msec of the first (i.e., during physiologic refractory period of myocardium) to determine the level of polarization. If the evoked-response (ER) amplitude is greater than 2.5 mV, the measured lead polarization is less than 4.0 mV, and the ratio of the ER/ER sensitivity is greater than 1.8 : 1, the device will automatically determine that the safety margin is acceptable and recommend Autocapture as a programmed feature. The Autocapture feature uses unipolar pacing from the tip electrode and determines capture on a beat-to-beat basis. If a ventricular stimulus is not followed by a detectable evoked response, a second test pulse is given at a value 0.25 V greater than the last threshold measurement, known as the automatic pulse amplitude (APA). If a pulse is not followed by detectable capture, a backup pulse is delivered within 80 to 100 msec at an amplitude of 4.5 V. If two consecutive APA pulses are not followed by an evoked response, the threshold is measured to determine whether the APA needs adjustment. Specifically, the pulse is incremented 0.25 V above the last APA. If capture is not confirmed, the APA is repeated in 0.125-V increments until two consecutive captured events occur. For these devices, all lossof-capture pulses are immediately followed by a backup pulse. A potential complicating factor with detection of the evoked response is differentiating fusion from capture. In the DDD(R) pacing mode, precisely timed intrinsic conduction can result in false detection of loss of capture. To differentiate true loss of capture from fusion, the atrioventricular (AV) delay is incremented by 100 msec after two consecutive loss-of-capture events to search for intrinsic conduction. If intrinsic conduction is indeed present during this extension of the AV delay, the backup pulse is eliminated. On the other hand, if subsequent backup pulses or APA increments are required due to loss of capture, the paced or sensed AV delay is shortened to either 50 or 25 msec, respectively. This sequence can complicate the interpretation of electrocardiographic tracings with irregular AV delays. However, knowledge of the function of the Autocapture algorithm allows recognition that this is a normal phenomenon. Automatic capture algorithms have also been applied by most other manufacturers. The Sorin Group pacemakers (Milan, Italy) detect the evoked response on the tip electrode of a unipolar lead, provided that the polarization properties of the electrode are favorable. Boston Scientific pacemakers (Natick, Mass.) use a lower-capacitance output

capacitor to minimize the afterpotentials on the ventricular lead as a method for improving detection of the evoked response. The smalleroutput capacitor increases the droop of the pacing pulse, but the afterpotential is greatly reduced. The smaller-output capacitor may have the effect of slightly increasing the apparent stimulation threshold, an effect that is usually measurable only when the pacing threshold exceeds 2.5 V. Other manufacturers offer variants of the automatic capture algorithm that do not deliver backup pulses on a beat-to-beat basis but provide automatic determination of pacing threshold at programmed intervals during the day. These devices determine the pacing threshold and adjust the pacing amplitude to provide a programmed margin of safety. In general, automatic capture algorithms function quite effectively and may reduce the risk of loss of capture due to fluctuations in pacing threshold caused by drugs, metabolic derangement, or lead dislodgment. The capability for reducing the programmed margin of safety is effective for prolonging battery life and may reduce the frequency of clinic follow-up visits. The Medtronic Ventricular Capture Management feature determines a strength-duration threshold at a programmable interval (nominally, once per day). After the amplitude threshold is determined at a pulse duration of 0.4 msec, the pulse amplitude is doubled and a pulse duration threshold is measured. The permanent ventricular stimulation amplitude is then automatically reprogrammed using a programmable amplitude safety margin (usually twice the threshold) or a programmable minimum amplitude, whichever is higher. The nominal values for ventricular capture management are a safety margin of twice the threshold with a pulse duration of 0.4 msec and a minimum ventricular amplitude of 2.5 V. During measurement of the pacing threshold, each test pulse is followed by a backup pulse 110 msec later to ensure that a pacing pause does not occur. If the automatically measured ventricular stimulation threshold is greater than 2.5 V at 0.4 msec, the ventricular output is automatically programmed to 5.0 V and 1.0 msec. The Medtronic Atrial Capture Management feature is designed to periodically measure the atrial stimulation threshold and adapt the atrial output to a programmable amplitude safety margin. This feature does not use the evoked potential to determine the presence or absence of atrial capture. Rather, the pacemaker searches for evidence that atrial test pulses reset the sinus node (Atrial Chamber Reset Method) or observes the ventricular response to determine whether a captured atrial test pulse is conducted to the ventricles through the AV conduction system. The Atrial Capture Management feature performs an atrial amplitude threshold at 0.4-msec pulse duration and after loss of capture is detected (defined as two of three test pulses indicating loss of capture); the amplitude setting is increased until atrial capture is confirmed. Because this feature does not rely on detection of the evoked response, there is no restriction on the type of atrial lead that can be used. This feature will not measure thresholds if the sinus rate is consistently faster than 87 bpm.

Adequate Margin of Safety A pacemaker must be programmed with a safety factor that allows for changes in pacing threshold. The clinician needs to know how much thresholds actually change in the acute to chronic period, as well as chronically on an hour-to-hour and day-to-day basis. Settings as low as 2.5 V and 0.5 msec at implantation appear to ensure capture for most adult patients with modern microporous, steroid-eluting leads. Higher values should be used with older-technology leads. Some patients have large variations in threshold. The factors involved in estimating how great a margin of safety to allow in programming are the (1) presently measured threshold, (2) probability of a catastrophe if pacing ceases, (3) patient’s ability to recognize intermittent loss of capture if occurring, (4) pharmacologic milieu, and (5) frequency of pacing threshold monitoring. In most patients, a 1.5 : 1 or 2 : 1 ratio of output voltage (Vo) to threshold voltage (Vthr), or output current to threshold current, provides a reasonable safety factor. The balance over



LONG-TERM AND DIURNAL VARIATIONS IN PACING THRESHOLD McVenes et al.241 found no significant threshold changes in adult canines using then-modern chronic atrial or ventricular leads as a function of eating, sleeping, or exercise. This finding is supported by Kadish et al.,242 who found no changes in chronic human pacing thresholds during a 24-hour period in four of five patients studied. Although in one patient the threshold at 0.6 msec changed from 1 to 1.5 V between 3 and 6 pm, these investigators concluded that “ventricular pacing thresholds do not show substantial diurnal variability.”242 Grendahl and Schaanning243 also found minimal variation in pacing threshold during the day, after meals, or during sleeping or physical activity.184 Shepard et al.76 reviewed 4942 pacing threshold measurements in 257 patients with 312 non-steroid-eluting leads at up to 295 months after implantation. The median in-use time was 17 months. Of the measurements, 1053 were in children younger than 12 years. At stimulus durations of 0.5 ± 0.04 msec, for thresholds measured 1 month or more after implantation, the mean threshold was 1.2 ± 0.66 V for endocardial electrodes and 2.8 ± 1.39 V for epicardially applied electrodes. Highest mean thresholds were in the 6- to 12-year-old age group. In patients with five or more measurements after 3 months of use, an increase in pacing threshold occurred after 3 months in 24%. An additional 21% had at least one threshold that exceeded the post3-months individual patient mean by three standard deviations. Other clinical events possibly related to threshold increases included a doubling of the threshold in a child during two successive summers, when mild cold–like symptoms began. The effects of various drugs on thresholds have been reported, but neither the test protocols nor the results have been consistent.244 Therefore, minimal literature appears to support the statistical validity of any particular safety factor.

35

On the basis of the earlier report of Preston et al.,239 Barold et al.245 suggested that Vo/Vthr must be at least 1.75 to ensure an adequate safety margin, assuming a 50% increase in energy at threshold throughout the day. Ohm et al.177,246 studied threshold evolution as a function of implant duration for an 8-mm2 polished platinum ring electrode and found that this lead had a peak threshold of 2.2 ± 0.75 V at a pulse duration of 0.5 msec measured 2 weeks after implantation. Assuming an output setting of 5 V and 0.5-msec pulse duration, the average patient had a Vo/Vthr of 2.3 : 1 during the peak threshold time. The 98th percentile patient (mean ± 2 standard deviations) had a Vo of 5 V and a Vthr of 2.2 ± 0.75 V, or a safety margin of about 1.35 : 1 at peak threshold. Unpredictable or unusual situations (e.g., myxedema) may occur that justify greater safety factor ratios.247 The important clinical point is that, for patients who are always or intermittently dependent on pacing to stay alive, a much greater pacing safety factor reduces the risk of otherwise unexplained sudden death. PROGRAMMING VOLTAGE VERSUS PULSE WIDTH FOR MAXIMUM PULSE GENERATOR LONGEVITY A common clinical concern for programming of the pulse generator to optimize battery longevity relates to whether it is more useful to program the amplitude or the duration of the output pulse. Based on examination of the strength-duration relationship, it is more efficient to reduce the Vo of the pulse, because the current drain varies as the square of voltage. Figure 1-33 illustrates the effect of doubling the Vthr (at a constant pulse width) or tripling the threshold pulse width (without changing voltage) on current drain. In this example, the rheobase voltage was determined to be 1 V and the chronaxie duration was 0.3 msec. The stimulation threshold was 4 V at a pulse duration of 0.1 msec or 2 V at 0.3 msec. Tripling the pulse duration at 4 V to 0.3 msec provided an adequate (2 : 1) safety margin with a current of 8 mA per pulse (4.8 µA continuous current) and a stimulus energy of 9.6 µJ. Similarly, doubling the Vthr at a pulse duration of 0.3 msec from 2 to 4 V yielded an identical current drain (8 mA/pulse, or 4.8 µA) and safety factor. If the patient had a higher threshold, for example 2 V at 1 msec, doubling of the voltage or tripling of the pulse width would still give the same current drain (12 µA), but the safety factor would be significantly different. Tripling the pulse width would provide a marginal (at best) safety margin, because threshold is approaching rheobase on the flat portion of the strength-duration curve. It would be necessary to double the voltage in this case to ensure a 2 : 1 safety margin. The foremost consideration for programming voltage and pulse duration is patient safety.

22 20 18

Volts, µJ

years is that of safety factor beyond threshold versus how long the pulse generator can be used. Again, clinical factors and patient reliability in checking need to be considered. Children may experience a higher rate of exit block because of their active inflammatory responses. In all patients, but especially children, use of steroid-eluting electrodes is recommended whenever possible.235-237 In a study reporting on 4953 threshold measurements made up to 20 years after implantation, long-term thresholds and threshold variations of non-steroid-eluting electrodes were found to be greater in children than in adults.76 The safety factors provided during the peak threshold phase are highest for steroid-eluting porous electrodes and lower for (in descending order) microporous electrodes, porous electrodes, and polished-tip electrodes, based on data represented in Figure 1-29. There may also be situations in which the patient’s pacemaker must be set at the maximum output at implantation (e.g., if the patient will not be available for follow-up). In these cases, an acceptable balance of safety margin and battery longevity might be obtained with a setting of 2.5 V and 0.5 msec for a steroid-eluting electrode, or a setting of up to 5 V and 0.5 msec with other leads. These numbers are at best only general guides. It is much better to arrange, by whatever means possible, for actual follow-up threshold measurements, both acutely and chronically. Modern perception of the range of chronic circadian threshold variation is based mainly on the work of Sowton and Norman238 (mid1960s), Preston et al.239 (late 1960s), and Westerholm240 (1971). The first two studies used constant-current generators and reported thresholds in terms of energy. Because the computed energy “thresholds” could have been a reflection of changes in impedance, the actual variation in voltage threshold cannot be determined from these studies. Westerholm, who reported both voltage and energy data, noted substantial circadian variations in both parameters. In all these studies, the leads were primarily epicardial/myocardial with polished electrodes. These human data, however, may be of marginal relevance to modern constant-voltage generators and porous, steroid-eluting electrodes.

1  Cardiac Electrical Stimulation

Energy (2× voltage)

16 14 12

Energy (3× PW)

10 8

Energy (threshold)

6 4

Threshold (V)

2 0

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 PW (msec) Figure 1-33  Effect on current drain and safety margin of programming the stimulus voltage to twice the threshold (at a constant pulse duration) or programming the pulse width (PW) to three times the threshold value (at the threshold voltage). See text for discussion.

36

SECTION 1  Basic Principles of Device Therapy

Summary Myocardial stimulation is the fundamental principle underlying artificial cardiac pacing. Perhaps the most important concept for programming of an implantable pacing system is a thorough understanding of the strength-duration relationship. Pulse generators allow the clinician to program both the pulse amplitude (in volts) and the pulse duration (in milliseconds). The stimulation threshold is a function of both these parameters. The exponential shape of the strength-duration curve must always be considered when programming the output pulse to ensure an adequate margin of safety between the delivered stimulus and the capture threshold. For example, pulse durations of 1 msec and greater are located on the flat portion of the strength-duration curve, whereas pulse durations of less than 0.15 msec are on the steeply rising portion of the curve. The practical importance of these facts can be appreciated by considering two points on the strength-duration curve shown in Figure 1-9. If the clinician determines the threshold to occur at point A (2 V and 0.5 msec) by decrementing the stimulus voltage at a constant pulse duration, programming of the pulse duration to 1 msec (point B) would provide very little margin of safety. Similarly, if the threshold is measured to be at point C (3.5 V and 0.15 msec) by decrementing the pulse duration at a constant voltage, doubling of the stimulation voltage to 7 V (point D) also would provide a poor safety margin. When one considers the shape of the strength-duration curve, a more appropriate programmed setting would be provided by doubling the threshold voltage at a pulse duration of 0.5 msec (point E, 4 V and 0.5 msec). As a general rule, if the threshold is determined by decrementing the stimulus voltage, an adequate margin of safety can be assumed by doubling the voltage if the pulse duration used was greater than 0.3 msec. The two most important points on the strength-duration curve (rheobase and chronaxie) are easily estimated with modern pulse generators (see Fig. 1-8). Rheobase can be estimated by decrementing the output voltage at a pulse duration of 1.5 to 2 msec. Chronaxie can then be estimated by determining the threshold pulse duration at twice the rheobase voltage. If instead the threshold is determined by decrementing the pulse duration, an adequate safety margin can be assumed by tripling the pulse duration only if the threshold is 0.15 msec or less. If the rheobase and chronaxie are measured, doubling of the threshold voltage at the chronaxie pulse duration provides an excellent method for programming a pacing system. In most circumstances, however, experienced clinicians will measure the pacing threshold at an initial stimulus duration of 0.4 or 0.5 msec, then make decisions based on their knowledge of the patient’s problems and medications. What constitutes an adequate safety factor depends on knowledge of the patient’s status. How dependent on the pacemaker is the patient? How medically stable is the patient? What medicines that can influence the pacing threshold is this patient taking? Have important threshold variations been seen, or are they anticipated in this patient after the initial stabilization period? Are there problems with the leads? How old is the pulse generator, and what is the known history of this pulse generator and attached leads in other patients? These factors determine clinical judgments about voltage and current safety, frequency of pacing and medical status monitoring, and early or late replacement of the pulse generator and leads. When programming the pulse generator at implantation, the clinician must also consider the acute to chronic evolution of the stimulation threshold. Because an acute rise in threshold typically occurs during the first several weeks after lead implantation, voltage and pulse duration may need to be programmed to higher values than needed for chronic pacing. The physician should reevaluate the stimulation threshold after the acute rise (and sometimes subsequent fall). For

most patients, the pacing system can be programmed to chronic output settings at a follow-up evaluation about 6 weeks after lead implantation. Although these recommendations may not be as applicable to patients receiving a steroid-eluting lead, caution is still warranted. The importance of drug and electrolyte effects on the strengthduration curve should also be appreciated. For patients requiring antiarrhythmic therapy, the stimulation threshold should be measured a number of times after drug initiation to ensure an adequate margin of safety for pacing. Similarly, patients who are more likely to experience alterations in electrolyte concentration (e.g., patients with renal failure, patients taking potassium-wasting diuretics) may need their pace­ makers to be programmed with a greater margin of safety. Perhaps most important, the degree to which the heart depends on pacing to sustain life or to prevent severe symptoms must be factored into the choice of a programmed margin of safety. For pacemakerdependent patients, a pacing pulse at least 2.5 times the chronic capture threshold is usually recommended. In contrast, patients unlikely to experience severe symptoms should failure to capture occur may have their pacemaker programmed to a lower margin of safety, perhaps twice the threshold. The effect of pacing rate on the stimulation threshold should also be considered for patients who require antitachycardia pacing, with the pacing threshold measured at all rates likely to be used. In the presence of high impedance caused by lead fracture, the current output of a constant-voltage pulse generator decreases. Loss of capture can occur. If lead insulation failure occurs, the impedance as seen by the pulse generator may decrease because of current shunting to noncardiac tissue. This results in an increase in the current from the pulse generator without a change in the nominal output voltage. This change may not be detected early if threshold is determined only by the voltage required for pacing capture. Measuring the voltage/current ratio allows detection of the nominal impedance and alterations in lead insulation or in wire continuity. Because some wire fractures intermittently make and break contact, a normal impedance measurement does not always ensure that the lead is intact. Pacing impedance is determined by four factors: (1) resistance in the conductor wire pathways, (2) polarization at the electrode-tissue interfaces, (3) resistance (small geometric size for high resistance) at the electrode-tissue interface, and (4) impedance/resistance of the tissues between the electrodes. The first two factors are energy inefficient, decreasing the current available for stimulation, whereas the third factor decreases current drain without decreasing the efficiency of stimulation. An ideal electrode would have, among other attributes, high resistance and high capacitance (low polarization voltage) at the electrode-tissue interface. Pacing with a monophasic stimulus is more energy efficient than pacing with a bipolar stimulus. The pacing threshold is greater at normal stimulus durations for biphasic stimuli than uniphasic stimuli with the same total duration. For successful defibrillation, biphasic stimuli are more energy efficient. A biphasic stimulus with proper characteristics reduces the postpulse ion rearrangements. Biphasic stimuli also may reverse continuing local and undesirable chemical processes at the electrode.

Conclusion Electrical stimulation, not only of the heart but also of other types of tissue (e.g., brain), is being used clinically more and more. Increasing knowledge of fundamental factors in electrical stimulation and practical developments for particular clinical circumstances is ongoing. Such knowledge will help cardiologists, as well as physicians and surgeons of other disciplines, make good decisions and expand the range of patient care.



1  Cardiac Electrical Stimulation

37

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Proc Natl Acad Sci USA 92:11220-11224, 1995. 128. Mehra R, Furman S: Comparison of cathodal, anodal, and bipolar strength-interval curves with temporary and permanent pacing electrodes. Br Heart J 41:468-476, 1979. 129. Kay GN: Basic aspects of cardiac pacing. In Ellenbogen KA, editor: Cardiac Pacing, Cambridge, MA, 1992, Blackwell Scientific. 130. Preston TA: Anodal stimulation as a cause of pacemakerinduced ventricular fibrillation. Am Heart J 86:366-372, 1973. 131. Bilitch M, Cosby RS, Cafferry EA: Ventricular fibrillation and competitive pacing. N Engl J Med 276:598-604, 1967.

132. Stokes K, Bird T, Taepke R: A new low threshold, high impedance microelectrode. In Antonioli GE, Reufeut AE, Ector H, editors: Pacemaker leads, Amsterdam, 1991, Elsevier, pp 543-548. 133. Bird T, Stokes KB: Ventricular electrode spacing and anode size [abstract 205]. Rev Eur Technol Biomed 3:63, 1990. 134. De Caprio V: Endocardial electrograms from transvenous pacemaker electrodes [PhD thesis in biomedical engineering]. 1977, Polytechnic Institute of New York. 135. Garberoglio B, Inguaggiato B, Chinaglia B, Cerise O: Initial results with an activated pyrolytic carbon tip electrode. Pacing Clin Electrophysiol 6:440, 1982. 136. Jones JL, Jones RE, Balasky G: Improved cardiac cell excitation with symmetrical biphasic defibrillation waveforms. Am J Physiol 253:H1418-H1424, 1987. 137. Knisley SB, Smith WM, Ideker RE: Effect of intrastimulus polarity reversal on electric field stimulation thresholds in frog and rabbit myocardium. J Cardiovasc Electrophysiol 3:239-254, 1992. 138. Tse HF, Lau CP, Leung SK, et al: Single lead DDD system: a comparative evaluation of unipolar, bipolar and overlapping biphasic stimulation and the effects of right atrial floating electrode location on atrial pacing and sensing thresholds. Pacing Clin Electrophysiol 19:1758-1763, 1996. 139. Izquierdo R, Rodrigo G, Pelegrin J, et al: Single lead DDD pacing using electrodes with longitudinal and diagonal atrial floating dipoles. Pacing Clin Electrophysiol 25:1692-1698, 2002. 140. Ripart A, Fletcher R: Sensing. In Ellenbogen KA, Kay GN, Wilkoff B, editors: Clinical cardiac pacing, Philadelphia, 1992, Saunders. 141. Barold SS, Ong LS, Heinle RA: Stimulation and sensing thresholds for cardiac pacing: Electrophysiologic and technical aspects. Prog Cardiovasc Dis 24:1, 1981. 142. Barold SS, Ong LS, Heinle RA: Stimulation and sensing thresholds for cardiac pacing: electrophysiologic and technical aspects. Prog Cardiovasc Dis 24:1, 1981. 143. Smyth NPD, Tarjan PP, Chernoff E, et al: The significance of electrode surface area and stimulating thresholds in permanent cardiac pacing. J Thorac Cardiovasc Surg 71:559, 1976. 144. Parsonnet V, Zucker IR, Kannerstein ML: The fate of permanent intracardiac electrodes. J Surg Res 6:285, 1966. 145. Thalen HJT, Van den Berg JW: Threshold measurements and electrodes of the cardiac pacemaker. Acta Pharmacol Nederl 14:227, 1966. 146. Akyurekli Y, Taichman GC, White DL, et al: Myocardial responses to sutureless epicardial lead pacing. In Meere C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp. 147. Furman S, Hurzler P, Parker B: Clinical thresholds of endocardial cardiac stimulation: a long-term study. J Surg Res 19:149, 1975. 148. Wilson GJ, MacGregor DC, Bobyn JD, et al: Tissue response to porous-surface electrodes: basis for a new atrial lead design. In Moore C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp. 149. Amundson D, McArthur W, MacCarter D, et al: Porous electrode-tissue interface. In Moore C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Monstreal, 1979, PaceSymp. 150. Amundson DC, McArthur W, Moshaffafa M: The porous endocardial electrode. Pacing Clin Electrophysiol 2:40, 1979. 151. MacGregor DC, Wilson GJ, Lixfeld W, et al: The porous surface electrode: a new concept in pacemaker lead design. J Thorac Cardiovasc Surg 78:281, 1979. 152. Breivik K, Ohm O-J, Engedahl H: Acute and chronic pulse-width thresholds in solid versus porous tip electrodes. Pacing Clin Electrophysiol 5:650, 1982. 153. Berman ND, Dickson SE, Lipton IM: Acute and chronic clinical performance comparison of porous and solid electrode design. Pacing Clin Electrophysiol 5:67, 1982. 154. Freud GE, Chinaglia B: Sintered platinum for cardiac pacing. Int J Artif Organs 4:238, 1981. 155. MacCarter DM, Lundberg KM, Corstjens JP: Porous electrodes: concept, technology and results. Pacing Clin Electrophysiol 6:427, 1983. 156. MacGregor DC, Pilliar RM, Wilson GJ, et al: Porous metal surfaces: a radical new concept in prosthetic heart valve design. Trans Am Soc Artif Intern Organs 22:646, 1976. 157. Elmqvist H, Schuller H, Richter G: The carbon tip electrode. Pacing Clin Electrophysiol 6:436, 1983. 158. Stokes KB, Bornzin G: The electrode-biointerface (stimulation). In Barold SS, editor: Modern cardiac pacing, Mt Kisco, NY, 1985, Futura, pp 33-78. 159. Cornacchia O, Maresta A, Nigro P, et al: Effect of propafenone on chronic ventricular pacing threshold in patients with steroideluting (capture) and conventional leads. Eur J Card Pacing Electrophysiol 2:A88, 1992. 160. Pearce JA, Bourland JD, Neilsen W, et al: Myocardial stimulation with ultrashort duration current pulses. Pacing Clin Electrophysiol 5:52-58, 1982. 161. Meyers GH, Parsonnet V: Engineering in the heart and blood vessels. New York, 1989, Wiley-Interscience. 162. Hurzeler P, Furman S, Escher DJW: Cardiac pacemaker current thresholds versus pulse duration. In Silverman HT, Miller IF, Salkind AJ, editors: Electrochemical bioscience and bioengineering, Princeton, NJ, 1973, Electrochemical Society, pp 124. 163. Barold SS, Winner JA: Techniques and significance of threshold measurement for cardiac pacing. Chest 70:760, 1976. 164. Brownlee WC, Hirst R: Six years experience with atrial leads. Pacing Clin Electrophysiol 9(6 pt 2):1239-1242, 1989.

165. Luceri RM, Furman S, Hurzeler P, et al: Threshold behavior of electrodes in long-term ventricular pacing. Am J Cardiol 40:184, 1977. 166. Bornzin GA, Stokes KB, Wiebusch WA: A low-threshold, lowpolarization platinized endocardial electrode [abstract]. Pacing Clin Electrophysiol 6:A-70, 1983. 167. Elmqvist H, Schuller H, Richter G: The carbon tip electrode. Pacing Clin Electrophysiol 6:436, 1983. 168. Mond H, Stokes KB: The electrode-tissue interface: the revolutionary role of steroid elution. Pacing Clin Electrophysiol 15:95107, 1992. 169. Ohm O-J, Breivik K: Pacing leads. In Gomez FP, editor: Cardiac pacing, electrophysiology, tachyarrhythmias, Madrid, 1985, Editorial Group, pp 971-985. 170. Hoff PI, Breivik K, Tronstad A, et al: A new steroid-eluting electrode for low-threshold pacing. In Gomez FP, editor: Cardiac pacing, electrophysiology, tachyarrhythmias, Mt Kisco, NY, 1985, Futura, pp 1014-1019. 171. Anderson JM: Inflammatory response to implants. ASAIO Trans 34:101-107, 1988. 172. Henson PM: Mechanisms of exocytosis in phagocytic inflammatory cells. Am J Pathol 101:494-514, 1980. 173. Robinson TF, Cohen-Gould L, Factor SM: Skeletal framework of mammalian heart muscle: arrangement of inter- and pericellular connective tissue structures. Lab Invest 29:482-498, 1983. 174. Preston TA, Judge RD: Alteration of pacemaker threshold by drug and physiologic factors. Ann NY Acad Sci 167:686-692, 1969. 175. Stokes KB, Anderson J: Low threshold leads: the effect of steroid elution. In Antonioli GE, editor: Pacemaker leads, Amsterdam, 1991, Elsevier, pp 537-542. 176. Sibille Y, Reynolds HY: Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis 141:471-502, 1990. 177. Benditt DG, Kriett JS, Ryberg C, et al: Cellular electrophysiologic effects of dexamethasone sodium phosphate: implications for cardiac stimulation with steroid-eluting electrodes. Int J Cardiol 22:67-73, 1989. 178. Stokes KB, Kriett JM, Gornick CA, et al: Low-threshold cardiac pacing electrodes. In Frontiers of Engineering in Health Care: Proceedings of the Fifth Annual Conference IEEE Engineering in Medicine and Biology Society, 1983. 179. Irnich W: Considerations in electrode design for permanent pacing. In Thalen HJT, editor: Proceedings of the IVth International Symposium on Cardiac Pacing, Assen, The Netherlands, 1973, Van Gorcum, pp 268. 180. Irnich W: Engineering concepts of pacemaker electrodes. In Schaldach M, Furman S, editors: Advances in pacemaker technology, New York, 1975, Springer-Verlag, pp 241. 181. Mond H, Sloman JG, Cowling R, et al: The small tined pacemaker lead: absence of displacement. In Meere C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp, pp 29-35. 182. Baker JH, Shepard RB, Plimb VJ, Kay GN: Effects of fixation mechanism and electrode material on atrial stimulation threshold: long-term evaluation in 338 patients [abstract]. Pacing Clin Electrophysiol 15:54, 1992. 183. Cornacchia D, Jacopi F, Fabbri M, et al: Comparison between active screw-in and passive leads for permanent transvenous ventricular pacing [abstract]. Pacing Clin Electrophysiol 6:A56, 1983. 184. EI Gamal M, Van Gelder L, Bonnier J, et al: Comparison of transvenous atrial electrodes employing active (helicoidal) and passive (tined J-lead) fixation in 116 patients [abstract]. Pacing Clin Electrophysiol E 6:205, 1983. 185. Kay GN, Anderson K, Epstein AE, Plumb VJ: Active fixation atrial leads: randomized comparison of two lead designs. Pacing Clin Electrophysiol 12:1355-1361, 1989. 186. Rasor NS, Spickler JW, Clabaugh JW: Comparison of power sources for advanced pacemaker applications. In Proceedings of the 7th Intersociety Energy Conversion Engineering Conference, Washington, DC, 1972, American Chemical Society, p 752. 187. Hirshorn MS, Holley LK, Hales JR, et al: Screening of solid and porous materials for pacemaker electrodes. Pacing Clin Electrophysiol 4:380, 1981. 188. Schaldah M: New pacemaker electrodes. Trans Am Soc Artif Intern Organs 17:29, 1971. 189. Helland J, Stokes KB: Nonfibrosing cardiac pacing electrode. US Patent No 4033357. February 17, 1976. 190. Elmqvist H, Schuller H, Richter G: The carbon tip electrode. Pacing Clin Electrophysiol 6:436, 1983. 191. Thuesen L, Jensen PJ, Vejby-Christensen H, et al: Lower chronic stimulation threshold in the carbon-tip than in the platinum-tip endocardial electrode: a randomized study. Pacing Clin Electrophysiol 12:1592-1599, 1989. 192. Bornzin GA, Stokes KB, Wiebush WA: A low threshold, low polarization, platonized endocardial electrode. Pacing Clin Electrophysiol 6:A70, 1983. 193. Mugica J, Duconge B, Henry L, et al: Clinical experience with new leads. Pacing Clin Electrophysiol 11:1745-1752, 1988. 194. Djordjevic M, Stojanov P, Velimirovic D, et al: Target lead-low threshold electrode. Pacing Clin Electrophysiol 9:1206-1210, 1986. 195. Amundson DC, McArthur W, Moshaffafa M: The porous endocardial electrode. Pacing Clin Electrophysiol 2:40, 1979. 196. Timmis GC, Helland J, Westveer DC, et al: The evolution of low threshold leads. Clin Prog Pacing Electrophysiol 1:313, 1983.



197. Berman ND, Dickson SE, Lipton IM: Acute and chronic clinical performance comparison of porous and solid electrode design. Pacing Clin Electrophysiol 5:67, 1982. 198. Freud GE, Chinaglia B: Sintered platinum for cardiac pacing. Int J Artif Organs 4:238, 1981. 199. Kay GN, Anderson K, Epstein AE, Plumb VJ: Active fixation atrial leads: randomized comparison of two lead designs. Pacing Clin Electrophysiol 12:1355-1361, 1989. 200. Stokes KB: Preliminary studies on a new steroid eluting epicardial electrode. Pacing Clin Electrophysiol 11:1797-1803, 1988. 201. Hamilton R, Gow R, Bahoric B, et al: Steroid-eluting epicardial leads in pediatrics: improve epicardial thresholds in the first year. Pacing Clin Electrophysiol 14:2066, 1991. 202. Stokes KB, Frohling G, Bird T, et al: A new bipolar low threshold steroid eluting screw-in lead. Eur J Card Pacing Electrophysiol 2:A89, 1992. 203. Schwaab B, Frohling G, Schwerdt H, et al: Long-term follow-up of a bipolar steroid eluting pacing lead with active and passive fixation. In Antoniolo GE, editor: Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 361-364. 204. Schwaab B, Frohling G, Schwerdt H, et al: Long-term follow-up of three microporous active fixation leads in atrial position. In Antoniolo GE, editor: Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 365-368. 205. Schwaab B, Frohling G, Schwerdt H, et al: Atrial and ventricular pacing characteristics of a steroid eluting screw-in lead. In Antoniolo GE, editor. Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 383-388. 206. Menozzi C: Comparison between latest generation steroideluting screw-in and tined leads: Long term follow-up. In Antoniolo GE, editor: Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 389-394. 207. Nurnberg JH, Schopper H, Busscher U, et al: Retrospective comparison of epicardial steroid-eluting and conventional leads for pacing after corrective surgery in congenital heart disease. Pacing Clin Electrophysiol 20:1193, 1997. 208. Wallace AG, Cline RE, Sealy WC, et al: Electrophysiologic effects of quinidine. Circ Res 19:960-969, 1966. 209. Gay RJ, Brown DF: Pacemaker failure due to procainamide toxicity. Am J Cardiol 34:728-731, 1974. 210. Moss AJ, Goldstein S: Clinical and pharmacological factors associated with pacemaker latency and incomplete pacemaker capture. Br Heart J 31:112, 1969. 211. Hellestrand KJ, Burnett PJ, Milne JR, et al: Effect of the anti­ arrhythmic agent flecainide acetate on acute and chronic pacing thresholds. Pacing Clin Electrophysiol 6:892, 1983. 212. Salel AF, Seagren SC, Pool PE: Effects on encainide on the function of implanted pacemakers. Pacing Clin Electrophysiol 12:1439, 1989. 213. Montefoschi N, Boccadamo R: Propafenone induced acute variation of chronic atrial pacing threshold: a case report. Pacing Clin Electrophysiol 13:480-483, 1990. 214. Huang SK, Hedberg PS, Marcus FI: Effects of antiarrhythmic drugs on the chronic pacing threshold and the endocardial R

1  Cardiac Electrical Stimulation wave amplitude in the conscious dog. Pacing Clin Electrophysiol 9:660, 1986. 215. Bianconi L, Boccadamo R, Toscano S, et al: Effects of oral propafenone therapy on chronic myocardial pacing threshold. Pacing Clin Electrophysiol 15:148-154, 1992. 216. Kubler W, Sowton E: Influence of beta-blockade on myocardial threshold in patients with pacemakers. Lancet 2:67, 1970. 217. Irnich W, Gebhardt U: The pacemaker-electrode combination and its relationship to service life. In Thalen HJT, editor: To pace or not to pace: controversial subjects in cardiac pacing, The Hague, 1978, Martin Nijhoff, pp 209. 218. Gay RJ, Brown DF: Pacemaker failure due to procainamide toxicity. Am J Cardiol 34:728-731, 1974. 219. Preston TA, Fletcher RD, Lucchesi BR, Judge RD: Changes in myocardial threshold: physiologic and pharmacologic factors in patients with implanted pacemakers. Am Heart J 74:235, 1967. 220. Khastgir T, Lattuca J, Aarons D, et al: Ventricular pacing threshold and time to capture postdefibrillation in patients undergoing implantable cardioverter-defibrillator implantation. Pacing Clin Electrophysiol 14:768-772, 1991. 221. Delmar M: Role of potassium currents on cell excitability in cardiac ventricular myocytes. J Cardiovasc Electrophysiol 3:474486, 1992. 222. Gettes LS, Shabetai R, Downs TA, et al: Effect of changes in potassium and calcium concentrations on diastolic threshold and strength-interval relationships of the human heart. Ann NY Acad Sci 167:693-705, 1969. 223. Lee D, Greenspan K, Edmands RE, et al: The effect of electrolyte alteration on stimulus requirement of cardiac pacemakers. Circulation 38:124, 1968. 224. Walker WJ, Elkins JT, Wood LW, et al: Effect of potassium in restoring myocardial response to a subthreshold cardiac pacemaker. N Engl J Med 271:597, 1964. 225. Surawicz B, Chelbus H, Reeves JT, et al: Increase of ventricular excitability threshold by hyperpotassemia. JAMA 191:71-76, 1965. 226. Westerholm CJ: Threshold studies in transvenous cardiac pacemaker treatment. Scand J Thorac Cardiovasc Surg 8(suppl):1, 1971. 227. Schlesinger Z, Rosenberg T, Stryjer D, et al: Exit block in myxedema, treated effectively by thyroid hormone replacement. Pacing Clin Electrophysiol 3:737-739, 1980. 228. Basu D, Chatterjee K: Unusually high pacemaker threshold in severe myedema: decrease with thyroid hormone therapy. Chest 70:677-679, 1976. 229. Nagatomo Y, Ogawa T, Kumagae H, et al: Pacing failure due to markedly increased stimulation threshold 2 years after implantation: successful management with oral prednisolone—a case report. Pacing Clin Electrophysiol 12:1034-1037, 1989. 230. Haywood J, Wyman MG: Effects of isoproterenol, ephedrine, and potassium on artificial pacemaker failure. Circulation 32(suppl II):110, 1965. 231. Katz A, Knilans TK, Evans JJ, Prystowsky EN: The effects of isoproterenol on excitability, supranormal excitability and

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conduction in the human ventricle [abstract]. Pacing Clin Electrophysiol 14:710, 1991. 232. Levick CE, Mizgala HF, Kerr CR: Failure to pace following high dose anti-arrhythmic therapy: reversal with isoproterenol. Pacing Clin Electrophysiol 7:252-256, 1984. 233. Daubert C, Ritter P, Cazeau S, et al: Permanent biventricular pacing in dilated cardiomyopathy: Is a totally endocardial approach technically feasible? Pacing Clin Electrophysiol 19:699, 1996. 234. McVenes R, Stokes K: Alternative pacing sites: how the modern technology deals with this new challenge. In Antonioli GE, editor. Pacemaker leads 1997, Bologna, 1997, Monduzi Editore, pp 223-228. 235. Hurzeler P, Furman S, Escher DJW: Cardiac pacemaker current thresholds versus pulse duration. In Silverman HT, Miller IF, Salkind AJ, editors: Electrochemical bioscience and bioengineering, Princeton, NJ, 1973, Electrochemical Society, pp 124. 236. Stokes KB, Church T: The elimination of exit block as a pacing complication using a transvenous steroid-eluting lead. Pacing Clin Electrophysiol 10:748, 1987. 237. Till JA, Jones S, Rowland E, et al: Clinical experience with a steroid eluting lead in children [abstract]. Circulation 80:389, 1989. 238. Sowton E, Norman J: Variations in cardiac stimulation thresholds in patients with pacing electrodes. In Digest of the 7th International Conference on Medical and Biological Engineering, 1967, Stockholm. 239. Preston TA, Fletcher RD, Luchesi BR, et al: Changes in myocardial threshold: physiologic and pharmacologic factors in patients with implanted pacemakers. Am Heart J 74:235-242, 1967. 240. Westerholm C-J: Threshold studies in transvenous cardiac pacemaker treatment. Scand J Thorac Surg Suppl 8(suppl):1-35, 1971. 241. McVenes R, Lahtinen S, Hansen N, Stokes K: Physiologic and drug induced changes in cardiac pacing and sensing parameters [abstract 324]. Eur J Card Pacing Electrophysiol 2:A86, 1992. 242. Kadish A, Kong T, Goldberger J: Diurnal variability in ventricular stimulation threshold and electrogram amplitude [abstract]. Eur J Card Pacing Electrophysiol 2:A86, 1992. 243. Grendahl H, Schaanning CG: Variations in pacing threshold. Acta Med Scand 187:75-78, 1970. 244. Barold S: Effect of drugs on pacing thresholds. In Antonioli GE, Aubert AE, Ector H, editors: Pacemaker leads 1991, New York, 1991, Elsevier, pp 73-86. 245. Barold SS, Ong LS, Heinle RA. Stimulation and sensing thresholds for cardiac pacing: Electrophysiologic and technical aspects. Prog Cardiovasc Dis 24:1, 1981. 246. Ohm O-J, Breivik K: Pacing leads. In Gomez FP, editor: Cardiac pacing, electrophysiology, tachyarrhythmias, Madrid, 1985, Editorial Group, pp 971-985. 247. Basu D, Chatterjee K: Unusually high pacemaker threshold in severe myedema: decrease with thyroid hormone therapy. Chest 70:677-679, 1976.

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2 

SECTION 1  Basic Principles of Device Therapy

Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms GREGORY P. WALCOTT  |  STEVEN M. POGWIZD  |  RAYMOND E. IDEKER

E

lectrical defibrillation is the only practical means for halting ventricular fibrillation (VF). Although it has been known for more than a century that application of an electric shock directly to the myocardium causes VF, and that the heart can be returned to normal rhythm by subsequent application of a shock of greater magnitude,1-3 knowledge of the mechanisms underlying the process of defibrillation was slow in developing. Only the introduction of novel techniques for the analysis of action potentials and activation sequences has allowed greater insight into the physiology of both fibrillation and defibrillation.4-8 It is hoped that this insight will result in a higher success rate for external defibrillation and improved design of implantable cardioverter-defibrillators (ICDs). A large part of current research is dedicated to determining the underlying reason for the success or failure of a defibrillating shock. VF is maintained by multiple activation fronts that are constantly moving in a pattern of reentry. Characteristics of the activation pattern and action potential are believed to be important determinants of whether a shock will successfully defibrillate the heart. A successful defibrillating shock is believed to extinguish most of these activation fronts, permitting the resumption of coordinated responsiveness.9-13 For the defibrillating shock to be completely successful, this must be accomplished without creating an environment that promotes susceptibility to reinitiation of fibrillation.9,10 It has been established that successful defibrillation requires that the shock results in adequate distribution of the potential gradient (a surrogate for local current flow) throughout the ventricular myocardium.14-16 Fundamentally, defibrillation is believed to be realized through an electrical pulse that causes an alteration in the transmembrane potential of myocytes. It most likely requires a rapid induction of changes in the transmembrane potential of the myocytes in a critical mass of myocardium (75%-90% of myocardium in dogs).13,14,16 Because this represents a large mass of tissue, depolarization must be achieved at a considerable distance from the stimulating electrode. To gain an understanding of this complex far-field process, various mathematical models have been generated and predictions of computer simulations compared with physiologic findings. Both discontinuities in the anisotropic properties of the extracellular and intracellular domains, as described by the bidomain model,17,18 and highly resistive discontinuities in the intracellular space (e.g., collagenous septa), as described in the secondary source model,19-21 may contribute to the far-field changes in the potential gradient that halt the activation fronts of fibrillation; these are discussed later. The mechanisms underlying degeneration into fibrillation in failed shocks remain incompletely understood. Residual wandering wavelets,22 nonuniform refractoriness,23 and areas of low potential gradient, in which critical points (centers of reentrant circuits) form,15 may be the sources of propagating wavefronts that can result in fibrillation through reentry. Centrifugal propagation from ectopic foci induced by the defibrillation shock may also play a role, especially in the atrium.10 This chapter expands on the subjects just mentioned, discussing characteristics of VF important to understanding defibrillation and characteristics of shock that lead to successful defibrillation, such as waveform shape and electrode configuration. A shock is traced from its origin at the defibrillation electrodes to its distribution through the

40

heart, with a discussion of its effect on the transmembrane potential and how it leads to the successful cessation of fibrillation.

Fibrillation Understanding defibrillation requires an understanding of fibrillation. Knowing the basic characteristics of VF and whether it is maintained by reentrant or focal activity, as well as the characteristics of the action potential and the excitability of the fibrillating tissue, helps to define the therapy that will be successful in stopping the arrhythmia. Ventricular fibrillation has been characterized as progressing through four stages, based on high-speed cinematography of electrically induced fibrillation in dog hearts24 (Fig. 2-1). A brief undulatory, or tachysystolic, stage lasting only 1 to 2 seconds occurs first. It is characterized by three to six undulatory contractions that resemble a series of closely occurring systoles and involve the sequential contraction of large areas of the myocardium. This is followed by a second stage of convulsive incoordination (15-45 seconds) during which more frequent waves of contraction sweep over smaller regions of the myocardium. Because the contractions in each region are not in phase, the ventricles are pulled in a convulsive manner. It is during this stage of fibrillation that the ICD shocks are given, about 10 to 20 seconds after the onset of fibrillation. In the third stage of tremulous incoordination, the independently contracting areas of the ventricular surface become even smaller, giving the heart a “trembling” appearance. Tremulous incoordination lasts for 2 to 4 minutes, before the fourth and final stage of atonic fibrillation occurs. Atonic fibrillation develops within 3 to 5 minutes after the onset of fibrillation and is characterized by the slow passage of feeble contraction wavelets over short distances. With time, the number of quiescent areas increases. Ischemia plays a role in the development of the third and fourth stages, because the fibrillating heart remains in the second stage if the coronary arteries are perfused with oxygenated blood.25,26 Driving the mechanical activity of the heart during fibrillation is the electrical activity of the myocardium. The electrical activity of the heart during fibrillation has been studied using both extracellular and optical recordings. Several groups have suggested that fibrillation is maintained by reentry. In most cases, reentry appears to be caused by “wandering wavelets” of activation, activation fronts that follow continually changing pathways from cycle to cycle. In some studies, the activation sequence appears moderately repeatable from cycle to cycle, following approximately the same pathway.27-29 Occasionally, a spiraling pattern of functional reentry emanates from the same region for several cycles. Sometimes, the central core of these spiral waves meanders across the heart.5 At other times, new reentrant activation fronts are generated when one front interacts with another during its vulnerable period. Study of VF suggests that there is a level of organization to the seemingly random patterns of wandering wavelets. Two competing hypotheses have been proposed to explain this organization. The “mother rotor” hypothesis was first proposed by Lewis30 in 1925 and revived in 1996 by Gray and Jalife.31 This hypothesis proposes that a single, stationary reentrant circuit (or mother rotor), located in the fastestactivating region of the heart, “drives” VF by giving rise to activation fronts that propagate throughout the remainder of the myocardium.29



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

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CELLULAR ACTION POTENTIAL AND EXCITABLE GAP DURING FIBRILLATION y y

W

y

y

X

B

A

C

D

E

F

Figure 2-1  Spread of waves in analysis of motion pictures obtained during four stages of fibrillation described by Wiggers. A, Spread of wavefront during initial, undulatory stage. B, Theoretical passage of impulses from point x to form a wavefront at y. C through F show the appearance of contraction waves in the small rectangular area W from A, magnified. C, Undulatory stage; D, convulsive stage; E, tremulous stage; F, atonic stage. (From Wiggers CJ: Studies of ventricular fibrillation caused by electric shock: cinematographic and electrocardiographic observations of the natural process in the dog’s heart—its inhibition by potassium and the revival of coordinated beats by calcium. Am Heart J 5:351-365, 1930.)

These wavefronts propagate away from this fast-activating region, encounter areas of unidirectional block, and break up into smaller, slower-moving waveforms that resemble Wiggers’ wandering wavelets. Experiments best demonstrating the “mother” rotor have been performed in small hearts, from guinea pigs or rabbits. Studies of larger hearts have shown areas of faster and slower activation across the heart, but the existence of a single reentrant rotor that drives fibrillation has not been clearly demonstrated.32,33 In contrast to the mother rotor hypothesis is the “restitution” hypothesis. Restitution properties of the heart have been recognized for many years. Restitution in the heart refers to the relationship between the duration of an action potential in a particular cell and the duration of the previous diastolic or resting interval. If the previous diastolic interval (DI) is short, the current action potential duration (APD) will also be short. If the previous DI is long, the current APD will be long. For a regular rhythm, the preceding DI is constant and, therefore, so is the duration of the subsequent APD. The relationship between an APD and the previous DI is often described graphically as a plot of APDn versus DIn-1 (Fig. 2-2). The steepness of the restitution curve is an important characteristic of this curve, especially at short DIs. If this slope is greater than 1, then, at a constant cycle length, a single perturbation in DI will cause the ensuing APDs and DIs to oscillate, with the oscillations progressively increasing until the site is refractory at the time of the next cycle, causing conduction block and VF initiation. During VF, it is hypothesized that, when the slope of the restitution curve is greater than 1, oscillations in DI and APD increase until block occurs and wavefronts break up. Figure 2-2 shows an example of a restitution curve recorded from the right ventricle of a pig. The relationship between a DI and the subsequent APD is well defined during paced rhythm but less well defined during VF. Understanding how VF is maintained may help develop new therapies that will make fibrillation easier to stop. If VF is maintained by a mother rotor, targeting of electrical therapy, either shocks or pacing, to the region that contains the dominant reentrant circuit may be successful in halting VF. If VF is started and maintained primarily by the DI restitution properties of the heart, drugs that decrease the slope of the restitution curve, especially at short coupling intervals, may be successful in halting VF.

In the past few years, knowledge of the characteristics of the action potentials during fibrillation has increased greatly. This is a direct result of the introduction of techniques for recording action potentials in whole hearts, either in vivo31 or in perfused, isolated hearts.4-6,10,31 During fibrillation, the action potentials are altered: the APD is decreased; the action potential upstroke is slowed (decreased firstorder derivative, dV/dt) and of decreased magnitude; the plateau phase is abbreviated; and DIs are abbreviated or absent (Fig. 2-3). During the first few seconds of VF (or atrial fibrillation), the activation rate is quite rapid; the mean cycle length of VF in patients undergoing defibrillator implantation was 213 ± 27 msec.6 DIs are rarely seen during early fibrillation, and the upstroke of most action potentials occurs before the transmembrane potential has returned to baseline from the previous action potential. The demonstration of an excitable gap in fibrillating atrial tissue,34 as well as evidence of an excitable gap in fibrillating ventricular tissue,35 suggests that there are periods late in the action potential in the fibrillating myocardium during which an electrical stimulus can capture a portion of the fibrillating myocardium. Knowledge of an excitable gap provides an opportunity to stimulate the tissue just in front of a fibrillating wavefront, to cause wavefront block. As described in Chapter 1, the electrical activity of the heart is controlled ultimately by ion channels located in the cell membrane of the myocyte. It has been established that both the voltage-gated fast channels (sodium [Na+]) and slow channels (Na+ and calcium [Ca2+]) are active during the first few seconds of VF.8 The fast-channel activity is indicated by the rapidity of the upstroke of the action potential (phase

200 180 160 APD60 (msec)

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140 120 100 80 60 40 0

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DI (msec) Figure 2-2  Restitution curve recorded from right ventricle of pig. Dynamic action potential duration APD60 restitution relationship during pacing and ventricular fibrillation (VF) in one animal. (APD60 is the action potential duration at 60% of return to resting membrane voltage.) Open circles represent data from pacing, and solid squares represent data throughout 60 seconds of VF. Data were recorded from the anterior right ventricle using a floating microelectrode. The heart was stimulated using decremental pacing at an initial pacing rate of 1 pulse every 450 msec. The stimulus-to-stimulus interval was progressively shortened until either the heart was refractory to the stimulation or VF was induced. Note that the open circles form an exponential relationship between the diastolic interval (DI) and APD60, whereas the relationship between DI and APD60 is not well defined during VF. (From Huang J, Zhou X, Smith WM, Ideker RE: Restitution properties during ventricular fibrillation in the in situ swine heart. Circulation 110:3161-3167, 2004.)

42

SECTION 1  Basic Principles of Device Therapy

I II III

MAP 250 msec ECM Figure 2-3  Recording during ventricular fibrillation in a human. Leads I, II, and III are body surface electrocardiograms. Note that there is no period of diastole between action potentials. MAP, Right ventricular monophasic action potentials; ECM, local bipolar electrogram. (From Swartz JF, Jones JL, Fletcher RD: Characterization of ventricular fibrillation based on monophasic action potential morphology in the human heart. Circulation 87:1907-1914, 1993.)

0) during early fibrillation and its sensitivity to administration of the Na+ channel blocker, tetrodotoxin. As fibrillation proceeds, the upstrokes of the action potentials become increasingly slower, with a decreased dV/dtmax, but the action potentials remain sensitive to tetrodotoxin until 1 to 5 minutes after initiation of fibrillation. A transition then occurs in which the action potential upstrokes become insensitive to tetrodotoxin. This suggests that the propagation of the action potential is no longer mediated primarily by the fast voltage-gated Na+ channels and may be mediated by slow voltage-gated Ca2+ channel activity in the later stages of fibrillation.4 The activation complexes recorded from the ventricular myocardium remain active only as long as the coronary arteries are perfused with oxygenated blood, suggesting that ischemia may be responsible for the loss of fast-channel activation during prolonged VF.26

Defibrillation As previously mentioned, application of a powerful electrical shock to the heart is the only reliable means of stopping fibrillation. Successful defibrillation can reflect either the immediate cessation of all activation fronts or the cessation of activation fronts after two to three cycles,11,36 followed by coordinated beating of the heart. Unsuccessful defibrillation can reflect a failure to inhibit the fibrillating activation fronts or the resumption of fibrillating activation fronts after their initial inhibition. WAVEFORMS, CURRENT STRENGTH, AND DISTRIBUTION DURING DEFIBRILLATION The two most common waveform shapes used clinically are the monophasic and biphasic waveforms. In monophasic waveforms, the polarity of the shock is unchanged at each electrode for the entire duration of the electrical shock. In biphasic waveforms, the polarity of the shock reverses at each electrode partway through the defibrillation waveform. Many studies, in both animals and humans, have shown that biphasic waveforms can defibrillate with less current and energy than monophasic waveforms, in both internal and transthoracic defibrillation configurations.37-40 Within each type, waveforms can be described as truncated exponential or damped sinusoidal shapes. ICDs use truncated exponential biphasic waveforms. Most external defibrillators have used damped sinusoidal monophasic waveforms, but because of the inductor necessary to shape the waveform, these defibrillators tend to be large and heavy. More recently, smaller, lighter external defibrillators have been developed that use truncated exponential biphasic waveforms similar to those used in ICDs. Damped sinusoidal biphasic waveforms are used in external defibrillators in Russia; similar to truncated exponential biphasic waveforms, these show improved efficacy over monophasic waveforms.41,42

However, not all biphasic waveforms are superior to monophasic waveforms, For example, if the second phase of the biphasic waveform becomes much longer than the first phase, the energy required for defibrillation increases and can eventually rise to a level greater than the energy required to defibrillate with a monophasic waveform (with duration equal to the first phase of the biphasic waveform).40,43,44 The optimum duration of the two phases of the biphasic waveform depends on the electrode impedance and the defibrillator capacitance.45-48 Several groups have shown that defibrillation efficacy for square waveforms follows a strength-duration relationship similar to that for cardiac stimulation;49,50 as the waveform becomes longer, the average current at the 50% success point (the current when one half of delivered shocks will succeed) becomes progressively less, approaching an asymptote called the rheobase.51 On the basis of this observation, some suggest that cardiac defibrillation can be mathematically modeled using a resistor-capacitor (RC) network to represent the heart45,51-53 (Fig. 2-4). As empirically determined, the time constant for the parallel RC network is 2.5 to 5 msec.45,47,53 In one version of the model,53 a current waveform is applied to the RC network. The voltage across the network is then calculated for each time point during the defibrillation pulse. The relative efficacies of different waveform shapes and durations can be compared by determining the current strength that is necessary to make the voltage across the RC network reach a particular value, called the defibrillation threshold. Several observations can be made from this model. First, for square waves, as the waveform duration becomes longer, the voltage across the network increases, approaching an asymptote, or rheobase. For truncated exponential waveforms, however, the model voltage rises, reaches a peak, and then, if the waveform is long enough, begins to decrease (see Fig. 2-4). Therefore, the model predicts that monophasic exponential waveforms should be truncated at a time when the peak voltage across the RC network is reached. Current or energy delivered after that point is wasted. In support of this prediction, strength-duration relationships measured in both animals53 and humans54 do not approach an asymptote but rather reach a minimum and remain constant as the waveform lengthens. This minimum occurs over a range of waveform durations and does not extend indefinitely. Schuder et al.55 showed that, if the duration of a waveform becomes too long, defibrillation efficacy decreases. Second, the model predicts that the heart acts as a low-pass filter.52 Therefore, waveforms that rise gradually should have better efficacy than waveforms that turn on immediately. This prediction has been shown to hold true for external defibrillation,56 internal atrial defibrillation,57 and internal ventricular defibrillation.58 Ascending ramps defibrillate with a greater efficacy than do descending ramps.58,59 Third, several groups have suggested that the optimal first phase of a biphasic waveform is the optimal monophasic waveform.46,53 If so, what does the model predict as the “best” second phase of a biphasic waveform? Empirically, the role of the second phase apparently is to return the model voltage response back to zero as quickly as possible, thereby maximizing the increased efficacy of the biphasic waveform over that of the monophasic waveform with the same duration as phase 1 of the biphasic waveform. If the network voltage does not reach zero, or if it overshoots zero, efficacy is lost. Swerdlow et al.47 showed in humans that the “best” phase 2 of a biphasic waveform returns the model response close to zero. Together, these models allow the clinician to choose optimal capacitor sizes for truncated exponential biphasic waveforms, the waveforms most often used in ICDs. The capacitor must be large enough to be able to raise the network voltage to its threshold value and still hold enough charge to drive the network voltage back to zero. For a 40-Ω interelectrode impedance and a network time constant of 2.8 msec, the minimum capacitor that can accomplish this has a capacitance of 75 microfarads (µF). These models can also help in choosing shock parameters, including phase duration for biphasic waveforms. Shock duration should be varied depending on defibrillation lead impedance; patients with low impedance should receive short-duration shocks, whereas patients

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Figure 2-4  Parallel resistor-capacitor (RC) network representation of heart. Responses of RC network to monophasic and biphasic truncated exponential waveforms with a time constant of 7 msec. The parallel RC network has a time constant of 2.8 msec. A, Input monophasic waveforms. The leading-edge current of the input waveform was 10 A. The waveforms were truncated at 1, 2, 3, 4, 5, 6, 8, and 10 msec.  B, Model response, V(t). Initially, as the waveform lengthens, V(t) increases until it reaches a maximum at about 4 msec, after which it begins to decrease. C, Input biphasic waveforms. The leading-edge current was 10 A. Phase 1 was truncated at 6 msec. Phase 2 was truncated after 1, 2, 3, 4, 5, 6, 7, and 8 msec. D, Model response does not change polarity until the phase 2 duration is longer than 2 msec. (From Walcott GP, Walker RG, Cates AW, et al: Choosing the optimal monophasic and biphasic waveforms for ventricular defibrillation. J Cardiovasc Electrophysiol 6:737-750, 1995.)

with high impedance should receive longer-duration shocks. Initially, the concept of “tilt” was used to vary shock phase durations with impedance. Tilt is defined as the quotient of the leading-edge voltage minus the trailing voltage at the end of the shock divided by the voltage at the beginning of the shock, expressed as a percentage. For example, a shock with starting voltage of 500 V and ending voltage of 100 V has a tilt of 80%. If tilt is held constant, shock duration varies linearly with shock impedance. Compared with model predictions (Fig. 2-5), fixedtilt waveforms are too short for patients with low impedance and too

long for patients with higher impedance. One defibrillator manufacturer has developed a reference table that gives waveform phase durations as a function of patient impedance using a model similar to the one previously presented.60,61 Their model uses “model time constants” of 2.5, 3.5, and 4.5 msec. It is recommended that the 3.5-msec constant be used first. If the defibrillation threshold for the 3.5-msec waveform is unsatisfactory, using the 4.5-msec constant is likely to be more effective than 2.5 msec. Waveforms that are too short tend to fail; waveforms that are too long tend to waste shock energy yet still defibrillate. The location of the defibrillation electrodes affects the magnitude of the shock necessary to defibrillate the heart. Typically, 200 to 360 J of energy are necessary for successful defibrillation, with the defibrillation electrodes located on the body surface, during transthoracic defibrillation with a damped sinusoidal monophasic waveform. Although less energy is required for a truncated exponential biphasic waveform,62 only about 4% to 20% of the current that is delivered to transthoracic defibrillation electrodes ever reaches the heart.63,64 Indeed, when the defibrillation electrodes are placed in the heart itself, usually only 20 to 34 J of energy is required, and the requirement may be as low as only a few joules when large, contoured epicardial electrodes are used.40,65 The strength of the shock also varies for different locations on or in the heart; epicardial patches defibrillate with a lower shock energy than transvenous electrode configurations.66 Although defibrillation efficacy is usually described by some measure of defibrillation shock “strength” (energy, voltage, or current), little insight into the mechanisms of defibrillation can be obtained from these measures. Knowing how the current (or voltage) of a defibrillation shock is distributed over the heart allows greater understanding of how defibrillation occurs. Several studies have measured the potential gradient distribution throughout the heart during a defibrillation shock.14,67,68 The potential gradient is a measure of the spatial variation of shock voltage across the heart. The potential gradient is measured in volts per centimeter (V/cm) of tissue. In a region with a high potential gradient, the difference in voltage between a given point and an area 1 cm distant from that point is high. Regions of low potential gradient have a measured voltage that is similar to that of nearby points. These studies show an uneven potential distribution for most electrode configurations, with areas of high potential gradient near the defibrillation electrodes and areas of low potential gradient in regions distant from the defibrillating electrodes. It has been hypothesized that a minimum potential gradient must be attained for successful defibrillation to occur, and that this requirement is independent of the current applied or the electrode configuration.15,16 After a shock that fails to defibrillate VF, the site of earliest activation immediately after the 65%

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2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

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44

SECTION 1  Basic Principles of Device Therapy

shock can be mapped and related to the electric field that was produced by the shock. For shocks near the defibrillation threshold, the sites of earliest activation after a failed shock occur in the areas of lowest potential gradient. The minimum potential gradient required for defibrillation is lower for biphasic than for monophasic waveforms (4 vs. 6 V/cm). A minimum potential gradient of 6 V/cm was required for successful defibrillation using a 10-msec truncated exponential monophasic waveform in the open-chest dog model.16 Similar findings were observed using a 14-msec truncated exponential monophasic waveform and multiple electrode configurations.15 In contrast, a minimum potential gradient of 4 V/cm was required for successful defibrillation using a truncated exponential biphasic waveform. Because higher shock strengths are required to induce a higher potential gradient, biphasic shocks successfully defibrillate with lower energy than monophasic shocks (i.e., a lower-voltage gradient is required). The requirement for a minimum potential gradient may reflect the need for a shock to prevent the generation of new activation fronts that can result in reinitiation of fibrillation.69 Examination of activation patterns after failed defibrillation for progressively larger shock strengths indicate that postshock activation occurs at numerous sites throughout the ventricle, and that reentry is common when the shock strength is much lower than that needed for defibrillation70 (Fig. 2-6). At shock strengths just lower than those required for defibrillation, postshock activation arises in a limited number of myocardial regions. The activation fronts then propagate to activate other regions of the myocardium for a few cycles before reentry occurs; activation becomes disorganized; and fibrillation is reinitiated. Although postshock activation sites can still arise in regions of lowest potential gradient after a shock slightly greater than that required for defibrillation, the cycles of activation that originate from these sites are slower. These activations terminate after a few cycles without reinitiating fibrillation.69-71 At least two inferences can be drawn from the model that the lowest potential gradient region determines whether or not a shock will halt fibrillation. First, different shock electrode configurations with the same defibrillation threshold (DFT) have the same lowest potential gradient value, but in different regions of the heart. Single-coil versus dual-coil defibrillator systems have similar DFTs. Mapping of postshock activations shows that the earliest recorded activity after the shock is the anterior left ventricle for dual-coil shocks but the posterior area for single-coil shocks.72 Thus the low gradient region presumably is anterior for dual-coil shocks and posterior for single-coil shocks, although this inference needs to be confirmed experimentally. Crossley et al.73 measured DFTs for shocks from either an electrode in the right ventricular (RV) apex or RV outflow tract to the pulse generator can and showed that DFTs were not significantly different for the two configurations. We can infer that the lowest potential gradient level was the same for each configuration, but likely in a different location. Second, high DFTs occur in some patients because either (1) the geometry of their heart is such that the low potential gradient region has a lower potential gradient than in most patients, or (2) these patients require a higher gradient level in the low gradient region to defibrillate. In either case, unusual lead configurations may help in these patients. A subcutaneous array can lower high DFTs,74 most likely by directing current to the left ventricular free wall. Likewise, an azygos vein electrode can be useful in lowering high thresholds,75 likely by directing current to the posterior portion of the heart. The previous discussion shows how defibrillation can fail because a shock is of insufficient strength. Another issue involves the defibrillation shock that becomes extremely large. At high shock strengths, the probability of defibrillation success again begins to decrease. It is believed that, at large strengths, defibrillation shocks can have detrimental effects on the heart. Increasing the shock strength to very high levels (>1000 V with transvenous electrodes) can result in activation fronts arising from regions of high potential gradient that reinduce VF.76 Cates et al.77 showed that, for both monophasic and biphasic shocks, increasing shock strength does not always improve the probability of successful defibrillation and may even increase the incidence

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Figure 2-6  Phase maps of single rabbit heart. Maps show the last cycle before a shock (left side) and the first cycle after a shock (right side) of 100 V (A), 200 V (B), 600 V (C), and 800 V (D) that failed to defibrillate. The defibrillation threshold was 800 ± 200 V in this series. Colors represent phase, and the symbols + and − indicate phase singularities or centers of reentrant circuits of opposite direction. Phase singularities as a marker of reentry were observed during ventricular fibrillation just before the shock in all cases. A and B, Postshock phase singularities were observed after failed 100-V and 200-V shocks. Visual analysis of animations of the optical recordings indicated that many of the phase singularities represented reentrant activations occurring immediately after the shock, so that the postshock interval was 0 msec. C and D, No phase singularities were observed after the 600-V and 800-V shocks. For the 600-V shock, activation propagated away in all directions from two early sites, at the apex and at the lateral base of the left ventricle, both of which appeared after a postshock interval of 42 msec. For the 800-V shock, a single wavefront of activation appeared at the apex and propagated away in all directions in a focal pattern after a postshock interval of 72 msec. (From Chattipakorn N, Banville I, Gray RA, Ideker RE: Effects of shock strengths on ventricular defibrillation failure. Cardiovasc Res 61:39-44, 2004.)

of postshock arrhythmias. Chapman et al.78 showed in dogs that the time required for the heart to recover hemodynamically after a defibrillation episode was shorter for biphasic than for monophasic shocks. Further, they showed that hemodynamic recovery took longer after high-energy shocks than after low-energy shocks. Reddy et al.79 showed that transthoracic defibrillation with biphasic shocks resulted in less postshock electrocardiographic evidence of myocardial dysfunction (injury or ischemia) than standard monophasic damped sinusoidal waveforms, and without compromise of defibrillation efficacy. One mechanism implicated in the means by which shocks cause damage to the myocardium is electroporation, the formation of holes or pores in the cell membrane. Electroporation may occur in regions where the shock potential gradient is high (>50 to 70 V/cm) and may even occur in regions where the potential gradient is much less than 50 V/cm.80 The very high voltage can result in disruption of the phospholipid membrane bilayer and in the formation of pores that permit



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

the free influx and efflux of ions and micromolecules. Electroporation can cause the transmembrane potential to change temporarily to a value almost equal that of the plateau of the action potential. At this transmembrane potential, the cell is paralyzed electrically, being both unresponsive and unable to conduct an action potential. Exposure of the myocardium to yet higher potential gradients, probably greater than 150 V/cm, results in arrhythmic beating, and at extremely high potential gradients, necrosis may occur.81 The shape of the waveform alters the strength of the shock at which these detrimental effects occur. Use of a 10-msec, truncated exponential monophasic waveform for VF in dogs resulted in conduction block in regions where the potential gradient was greater than 64 ± 4 V/cm.82 Shocks that created even higher potential gradients in the myocardium (71 ± 6 V/cm) were required for conduction block when a 5-msec/5msec, truncated exponential biphasic shock was used. Adding a second phase to a monophasic waveform, thereby making it a biphasic waveform, reduced the damage sustained by cultured chick myocytes compared with that induced by the monophasic waveform alone.83 Therefore, biphasic waveforms are less likely to cause damage or dysfunction in high-gradient regions than monophasic waveforms. MODELS PROPOSED TO EXPLAIN INDUCTION OF CHANGES IN TRANSMEMBRANE POTENTIAL THROUGHOUT HEART DURING DEFIBRILLATION SHOCK A shock in the form of a square wave given across the defibrillation electrodes appears almost immediately as a square wave in the extracellular space of the heart. There is no significant distortion, because the extracellular space throughout the body is primarily resistive, with little reactive component. Phase delays and alterations of the appearance of the shock wave occur in the transmembrane potential, however, because of the capacitance and ion channels of the myocyte membrane.84 Consequently, a square-wave shock can elicit an exponential change with time in the transmembrane potential (Fig. 2-7). The nonlinear behavior of the membrane caused by the ion channels also affects the outcome of reversing the polarity of the defibrillation shock. Reversing the polarity may reverse the sign of the change in the transmembrane potential in some regions of the myocardium, and

Extracellular space

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B Figure 2-7  Effect of square-wave shock on extracellular potential and transmembrane potential. The square-wave shock appears immediately as a relatively undistorted square wave in the extracellular space. It appears as an exponentially increasing change in the transmembrane potential. When a shock of a given polarity is delivered during the action potential plateau (A), the depolarization obtained is different in magnitude and time course from the hyperpolarization obtained with a shock of the opposite polarity (B). (From Walcott GP, Knisley SB, Zhou X, et al: On the mechanism of ventricular defibrillation. Pacing Clin Electrophysiol 20:422-431, 1997.)

45

the nonlinear behavior of the membrane can alter the magnitude and the time course of this change. As discussed previously, reversing the polarity of the shock may not reverse the sign of the change in the transmembrane potential in all regions of the heart; some areas may be hyperpolarized with both shock polarities.85 This may reflect the nonlinear behavior of the membrane ion channels. Several models have been formulated in an attempt to explain the mechanisms by which the defibrillation shock is distributed throughout the myocardium to restore coordinated, effective action potentials. As yet, none of the models adequately describes all the experimental findings on the action potential changes during defibrillation. It is well established experimentally that changes occur many centimeters from the defibrillating shock electrodes. These changes in transmembrane potential can result in new action potentials or prolongation of the action potential as described previously.23,86 Direct excitation can be observed,23 even far from the electrode (>30 mm),87 as well as across the entire heart.88 Although the one-dimensional cable model described in Chapter 1 adequately describes the generation of self-propagating action potentials close to an electrode as required for pacing, it fails to account for the far-field changes observed during defibrillation. During stimulation or defibrillation, this model predicts that the tissue near the anode should be hyperpolarized, whereas the tissue near the cathode should be depolarized.89 The magnitude of the hyperpolarization or depolarization decreases exponentially with the distance from the electrodes according to the membrane space constant, the distance at which the hyperpolarization or depolarization has decreased by 63%. For cardiac tissue, the space constant is only 0.5 to 1 mm.89,90 Therefore, the onedimensional cable equations predict that tissue more than 10 space constants (~1 cm) distant from the defibrillation electrodes should not directly undergo changes in transmembrane potential because of the shock field. That is, new action potentials should not arise by direct excitation at distances greater than 1 cm from the electrodes. This model fails to describe the experimentally observed global distribution of action potentials during defibrillation. Therefore, several additional mathematical formulations have been proposed, including the sawtooth model,21,91-93 the formation of secondary sources at barriers in the myocardium,20,94 and the bidomain model,95 to explain how a defibrillation shock affects the transmembrane potential a long distance from the shocking electrodes. In the simplest formulation of these models, the extracellular and intracellular spaces are considered to be low-resistance media and the membrane to be a high-resistance medium in parallel with capacitance. The simple case models incorporate only passive myocardial properties. The models have been rendered more realistic by the addition of active components to represent the ion channels in the membrane, gap junctions, and membrane discontinuities.96,97 By convention, the current is defined as the flow of positive ions from the anode to the cathode. Sawtooth Model The one-dimensional cable model positions two low-resistance continuous spaces that conduct current from the shock, the intracellular space and the extracellular space, separated by a high-resistance cell membrane. In the sawtooth model the intracellular space is divided by a series of high-resistance barriers, the gap junctions. Because of these high-resistance barriers, current moving in the intracellular space is forced to exit into the extracellular space and reenter the cell on the other side of the barrier. Exit and reentry of the current from the intracellular domain results in hyperpolarization near the end of the cell closest to the anode and depolarization near the end of the cell closest to the cathode. A tracing of the changes in transmembrane potential along a fiber during the shock should therefore resemble the teeth of a saw, with each tooth corresponding to an individual cell21,91-93 (Fig. 2-8). Increases in the junctional resistances are predicted to increase the magnitude of the potential changes at the ends of the cell.21 Although gap junctions are of low resistivity, they can present significant junctional resistance under certain conditions, such as hypoxia98,99 and calcium depletion.100 As the resistance of the gap junctions

SECTION 1  Basic Principles of Device Therapy

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Figure 2-8  Sawtooth model of transmembrane potential during a shock. A, Transmembrane potential shown is a summation of the membrane potential profile of the cable model and the periodicity arising from the periodic changes in intracellular resistance. The anode is to the left and the cathode is to the right in this one-dimensional model. The fiber is divided into 31 cells of equal length separated by junctions of high resistance. In the figure, the junctional resistance is shown much greater than is believed to occur in cardiac fibers, to allow the sawtooth pattern to be seen. B, Two parts of the summation in panel A are shown; Vm0, transmembrane potential profile of cable model; Vm1, periodicity arising from periodic changes in intracellular resistance. (Modified from Krassowska W, Pilkington TC, Ideker RE: Periodic conductivity as a mechanism for cardiac stimulation and defibrillation. IEEE Trans Biomed Eng 34:555-560, 1987.)

increases, it is predicted that a greater fraction of current passes preferentially across the cell membrane rather than along the cell. The sawtooth model adequately describes the requirement for a minimum potential gradient, because the magnitudes of the hyperpolarization and polarization at the ends of the cells are directly proportional to the strength of the stimulus. It also adequately describes the generation of action potentials at a distance from the electrodes and the differences in threshold stimuli between cathodal and anodal stimulation. Sawtooth changes in transmembrane potential have been observed in preparations of isolated cardiomyocytes;101,102 however, such a pattern in isolated cells would be consistent with the cable model. This pattern has not been observed in a syncytium of cardiac cells.20,103,104 Secondary Source Model Although the resistivity of the gap junctions at the boundaries between the cells may not adequately explain the physiologic effects of defibrillation, the resistivity of other intracellular discontinuities and

interruptions may well play a role. Most theories concerning the generation of action potentials and their propagation across the ventricle, such as the bidomain theory described later, consider the myocardium to be a uniform electrical continuum. This assumption does not take into account the discontinuities of the intracellular domain, where the myocardium is interrupted by barriers such as connective tissue septa, blood vessels, and scar tissue. As described previously for the sawtooth model, the intracellular current, on encountering such a barrier, must leave the intracellular space, cross the barrier, and reenter the intracellular domain on the other side. Depolarization should occur on one side of the barrier and hyperpolarization on the other side. Therefore, the barrier acts as a set of electrodes during the shock, becoming a secondary source of action potentials (Fig. 2-9). These secondary sources are important causes of depolarization and hyperpolarization throughout the myocardial tissues during a shock.20 The resistive barriers act in a manner similar to that described for the sawtooth model. In this case, however, the resistive barriers represent larger discontinuities, which tend to increase with age and cardiac hypertrophy.105 Computer simulations have shown that the cathodal stimulation delivered to the myocardium near an oval scar results in three distinct activation fronts: the primary activation front and secondary fronts at the distal and proximal edges, which are generated by the exit and reentry of current from the intracellular and extracellular spaces106 (see Fig. 2-8). Optical techniques have directly recorded changes in transmembrane potentials throughout a monolayer of ventricular myocytes.20 Localized regions of depolarization and hyperpolarization coincided with discontinuities in the monolayer, resulting in slow conductance. Microscopic regions of depolarization and hyperpolarization have also been observed in isolated slabs of left ventricle, although their correlation with anatomic structures was not possible using optical mapping techniques because of the light-scattering properties of myocardium.107 The significance of secondary sources was demonstrated in whole hearts by mapping of action potentials and determination of shock thresholds before and after the generation of a transmural lesion in the myocardial walls of dogs.94 Generation of the lesion resulted in the development of a region of direct activation in the area of the lesion, in addition to the region of direct activation resulting from the stimulating electrode observed before the lesion. Furthermore, the strength of the shock required to cause direct

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Figure 2-9  Computer model of secondary sources adjacent to scar elicited by single, large, pacing pulse. Area to the right represents myocardium that contains a rectangular scar (stippled region). On the left is the blood pool with a pacing catheter in it. Note that a pacing pulse depolarizes not only tissue near the cathode but also tissue near the scar. (From Street AM: Effects of connective tissue embedded in viable cardiac tissue on propagation and pacing: implications for arrhythmias. Durham, NC, 1996, Department of Biomedical Engineering, Duke University, p 134.)



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

10

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Figure 2-10  Isochronal activation maps. Maps obtained after cathodal stimulation before and after creation of a transmural incision that caused secondary sources adjacent to the lesion. Isochrones are drawn at 5-msec intervals, timed from the onset of the S1 or S2 stimulus. Arrows represent direction of activation. Darkened regions represent areas directly activated by the stimulus. Black vertical bars represent the approximate location of the transmural incision. A, S1 stimulus delivered before incision. B, 75-mA S2 stimulus delivered before incision. C, 250-mA S2 stimulus delivered before incision. D, S1 stimulus delivered after incision. E, 75-mA S2 stimulus delivered after incision. F, Orientation of the long axis of myocardial fibers. (From White JB, Walcott GP, Pollard AE, et al: Myocardial discontinuities: a substrate for producing virtual electrodes to increase directly excited areas of the myocardium by shocks. Circulation 97:1738-1745, 1998.)

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activation in the area of the lesion was less than one half of that required before generation of the lesion (Fig. 2-10). The effects of secondary sources have major implications for the probability of successful defibrillation at different shock strengths in individual patients, particularly elderly patients, as well as the potential for reentry. Furthermore, the size and placement of operative lesions may play significant roles in the success of subsequent defibrillation. Bidomain Model The bidomain model is an extension of the one-dimensional cable model into two or three dimensions. That is, the extracellular and intracellular spaces are represented as single, continuous domains that extend in two or three dimensions and are separated by the highly resistive cell membrane95 (Fig. 2-11). If the conductivities of the intracellular and extracellular spaces are constant in all directions, the

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Figure 2-11  Circuit diagram of two-dimensional bidomain model. Top of the resistor network represents the extracellular space; bottom of network represents the intracellular space. The symbol reΔx represents the extracellular resistivity in the x direction; reΔy represents the extracellular resistivity in the y direction; riΔx and riΔy represent the intracellular resistivities in the x and y directions. The rectangles represent the cell membrane. For a passive model, the rectangle would be replaced by a parallel resistor-capacitor network. For an active model, the rectangle would be replaced by a membrane ion model.

F

model collapses to the one-dimensional cable model. Anisotropy refers to the manner in which conductivities change with the direction of myocardial fiber orientation. Clerc108 showed that conductivity is higher in the direction parallel to the long axis of myocardial fibers (longitudinal) than in the direction perpendicular to the fibers (transverse) for both the intracellular and extracellular spaces. If conductivities change with direction but change the same for the intracellular and extracellular spaces, the bidomain model collapses to the onedimensional cable model. Studies have shown that the anisotropy ratio in ventricle is about 3 : 1 in the extracellular space and 10 : 1 in the intracellular space. When anisotropy ratios are used, the bidomain model begins to give new insights into how shocks change the transmembrane potential. Similar to the one-dimensional cable model, the bidomain model predicts that hyperpolarization occurs in tissue that lies under the extracellular anodal electrode. Likewise, depolarization occurs in tissue under the extracellular cathodal electrode. Unlike the one-dimensional cable model, the bidomain model also predicts that depolarization occurs along the long axis of the myocardial fibers at distances just a few millimeters from the anode. A similar effect is predicted to occur at the cathode, with hyperpolarization at distances of a few millimeters.109 Therefore, the effect on the transmembrane potential near the shocking electrode is predicted to be much more complicated by the bidomain model than by the one-dimensional cable model. The power of the bidomain model, however, is that it hypothesizes that there should be changes in the transmembrane potential, either hyperpolarization or depolarization, across the entire heart. In this model, the change in transmembrane potential elicited by the shock depends on the distribution of intracellular and extracellular current, which is affected by the change in potential gradient with distance, the distance from the electrode, and the orientation of the myocardial fibers. Experimental studies show a complex pattern of transmembrane potential changes during the delivery of a defibrillation shock, similar to those predicted by the bidomain model.85,110,111 The transmembrane potential changes that occur during the delivery of a defibrillation shock can lead to the initiation of reentry and subsequent reinitiation of fibrillation after the shock. Reentrant circuits can be described by the mathematical concept of a phase singularity.112 Phase can be used to describe the cardiac action potential, with 0 phase assigned to the upstroke of the action potential and 2Π phase assigned to the end of the action potential. A reentrant circuit can be thought of as a circle of phase starting at 0 (excitation) and continuing

48

SECTION 1  Basic Principles of Device Therapy

Postshock transmembrane voltage (mV´)

Postshock activation isochronal maps (5 ms) 1st beat 2nd beat 125 11.5  11.5 mm

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0

75 mV´

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Shock Figure 2-12  Creation of shock-induced phase singularity. Left upper panel shows the change in transmembrane potential at the end of a +100/−200 V biphasic shock (i.e., at 15th msec of 16-msec shock), which resulted in a single extra beat. Scale is shown in millivolts, calibrated to a control 100-mV action potential. Point of phase singularity is indicated by the black circle. Middle upper panel shows a 5-msec isochronal map that depicts the initiation of the postshock spread of activation. The map starts at the onset of the 8-msec phase 2 of the shock (polarity reversal). Lower panels show optical recordings from several recording sites used to reconstruct the activation maps. Right upper panel shows a continuation of the reentrant activation shown in the middle panel. Reentrant activity self-terminates after encountering refractory tissue in the lower right corner of the field of view (see traces in right lower panel). (From Efimov IR, Cheng Y, Van Wagoner DR, et al: Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure. Circ Res 82:918-925, 1998.)

to 2Π (recovery). The reentrant circuit moves around a central point, called a phase singularity. Efimov et al.110 showed that a defibrillation shock can impose changes on the transmembrane potential extending from 0 phase through 2Π phase (Fig. 2-12). Thus, a reentrant circuit is generated and fibrillation induced. The authors suggest that induced reentrant circuits may be one way that defibrillation shocks can fail. The secondary source and bidomain models may not be mutually exclusive; rather, both may contribute to the changes in transmembrane potential. The exact mechanism by which an electrical pulse results in defibrillation remains incompletely understood at the level of the cell membrane and the ion channels. As the transmembrane potential attains values closer to the typical resting transmembrane potential than the usual minimum of −65 mV observed in fibrillating myocytes, this may allow the voltage-gated Na+ channels to recover sufficiently and the myocytes to regain full excitability. EFFECT OF DEFIBRILLATING SHOCK FIELD ON CELLULAR ACTION POTENTIAL The final common pathway of changes in the transmembrane potential caused by a defibrillation shock involves effects on the shape and duration of the cellular action potential. The shock can have one of three effects on the myocardium, depending on the local strength of the shock and its timing with respect to the local action potential. If the shock is delivered during the early plateau, there will be little or no prolongation of the action potential. If the shock is strong enough and is delivered relatively late during the action potential, it will initiate a new action potential. A shock that is strong enough but is delivered during early phase 3 of the action potential will modify and prolong an ongoing action potential without initiating an entirely new action potential (Fig. 2-13).

To defibrillate the heart successfully, a defibrillating shock (1) must stop most or all activation wavefronts on the heart and (2) must not reinitiate fibrillation. The extension of refractoriness hypothesis helps to explain how a shock can stop fibrillation. A shock can prolong the refractory period of an action potential without triggering a new potential if it is of sufficient strength and is delivered at an appropriate interval with respect to the upstroke.23,113 If the first activation front that forms after a defibrillation shock encounters tissue with an extended refractory period, the front will be stopped because it cannot propagate into the region of refractory tissue. Also, a defibrillation shock must not restart fibrillation. If only part of the front encounters tissue with an extended refractory period, only part of the front will be halted. The rest of the activation front will propagate forward and will eventually move into the area that could not be stimulated or that would not allow propagation (unidirectional block). This process of stimulating some tissue and creating unidirectional block in adjacent regions creates a reentrant circuit that eventually breaks down into fibrillation. The critical point is that point at which a critical shock strength intersects a critical level of refractoriness, leading to the formation of a reentrant circuit.114-116 Optical mapping has revealed another type of critical point about which reentry can occur in response to the shock electric field.110 This type of critical point is formed when the shock electric field causes a large region of hyperpolarization immediately adjacent to a large region of depolarization. According to Efimov et al.,117 a biphasic shock waveform is more efficacious because the second phase of the shock obliterates the regions of hyperpolarization and depolarization so that the critical-point reentrant wavefront does not arise. Both types of critical points share two attributes; first, they produce a wavefront that appears immediately after the shock, and second, the wavefront forms a reentrant circuit.



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms 1.6 V/cm, 2 msec

S1-S2 (ms)

0 (mV)

222 225

80

A

100 msec 8.4 V/cm, 2 msec S1-S2 (ms) 90 110 130, 150, 170 180 200 210 220 230

(mV)

0

80

B

230 90 S1-S2 (msec) 100 msec

Figure 2-13  Transmembrane recordings from guinea pig papillary muscle. Recordings show an all-or-none response to a weak field stimulus and action potential prolongation in response to a larger stimulus. A, Recordings that illustrate the response to an S2 stimulus of 1.6 V/cm oriented along the fibers. The S1-S2 stimulus interval for each response (milliseconds) is indicated to the right of the recordings. The responses are much different, even though the change in S2 timing was only 3 msec. An S1-S2 interval of 222 msec caused almost no response, whereas an interval of 225 msec produced a new action potential.  B, Range of action potential extensions produced by an S2 stimulus generating a potential gradient of 8.4 V/cm oriented along long axis of myofibers; recordings from same cell as in A. The action potential recordings, obtained from one cellular impairment, are aligned with the S2 time. An S1 stimulus was applied 3 msec before phase 0 of each recording. The longest (230 msec) and shortest (90 msec) S1-S2 intervals tested are indicated beneath their respective phase 0 depolarizations. The S1-S2 interval for each response is indicated to the right. (From Knisley SB, Smith WM, Ideker RE: Effect of field stimulation on cellular repolarization in rabbit myocardium: Implications for reentry induction. Circ Res 70:707-715, 1992.)

REFIBRILLATION CAUSED BY DEFIBRILLATION SHOCK Although activation wavefronts consistent with the two types of critical points are observed following shocks given during the vulnerable period of paced rhythm and after shocks much weaker than the DFT during VF, these wavefronts are usually not observed after shocks near DFT strength during VF.118-123 Instead, earliest activation is not recorded until 50 to 60 msec after the shock, an interval called the isoelectric window, and wavefronts spread centrifugally away from this early site in a focal activation pattern. This pattern is present not only in electrical epicardial recordings (Fig. 2-14) but also in optical epicardial recordings (Fig. 2-15), which are not subject to saturation of the amplifiers by the shock as are electrical recordings. This activation pattern may represent epicardial breakthrough of an intramural reentrant circuit caused by a critical point. However, the same focal activation pattern has been observed in three-dimensional transmural electrical

49

recordings with plunge needles, during which an isoelectric window was also observed intramurally.122 This window has also been observed in optical recordings of a thin layer of spared epicardial tissue in which the intramural myocardium was frozen.123 Following a failed shock slightly weaker than the DFT, the focal activation pattern is seen for several cycles before the less organized pattern of VF reappears (see Fig. 2-14). However, this same focal activation pattern can be observed for one or more cycles after a successful defibrillation shock (see Fig. 2-15, B). These findings suggest that the failed shock reinitiates VF by causing a trigger (the focus) that interacts with the substrate (the ventricular tissue). If the trigger focus lasts long enough for reentry to develop in the ventricular myocardium substrate, the shock fails. If the trigger focus halts before reentry is induced in the myocardial substrate, the shock succeeds. This concept raises the possibility that cardiac disease or drugs can alter DFT by altering the trigger, the substrate, or both. For example, conditions that increase the number of cycles of the focal trigger or that decrease the cycle length of the trigger might increase DFT. Similarly, conditions that allow more easily induced reentry in the substrate, such as an increased dispersion of refractoriness, could also increase DFT. Although several mechanisms have been hypothesized, the cause of the focal activations after the shock is not definitively known, nor is it known why increasing the shock electric field decreases the number of focal postshock activations. One hypothesis is that the focus is not a true focus but arises from “tunnel propagation.”124 According to this hypothesis, a small part of a VF activation wavefront is not extinguished but propagates intramurally during the postshock isoelectric window, where it is undetected by three-dimensional mapping because it is so small. When sufficient tissue recovers, it is able to break out as a large wavefront. This wavefront appears to arise focally because the small, slowly propagating tunnel of activation is not detected by mapping. According to this hypothesis, a biphasic waveform has a lower DFT than a monophasic waveform because it decreases the number and size of the tunnels for the same-strength shock. However, the finding at multiple focal cycles is difficult to explain with the tunnel propagation hypothesis; multiple focal cycles, not just one, are present after the shock (see Fig. 2-14). Another hypothesis is that the focal activation arises where an intracellular calcium (Cai) “sinkhole” is present after the shock.123 This hypothesis is based on optical recordings demonstrating that Cai decreases during the isoelectric period in the region where the focus will later appear (Fig. 2-16). After the formation of the sinkhole, the action potential in this region is immediately preceded by an increase in Cai, suggesting the potential arises from triggered activity. According to this hypothesis, a biphasic waveform has a lower DFT than a monophasic waveform because it causes less postshock heterogeneity in Cai.125 In one study the DFT after VF of 10 seconds was significantly decreased by flunarizine, a drug that prevents activity triggered by delayed afterdepolarization (DAD).126 However, another study did not find that DFT after 10 seconds of VF was altered either by flunarizine or by pinacidil, a drug that prevents activity triggered by early afterdepolarization (EAD).127 A third study found that DFT after 20 seconds of VF was not altered by flunarizine, but that DFT was reduced by flunarizine after 7 minutes of VF by 82%.128 This suggests that after long-duration VF, but not short-duration VF, the focal postshock activation may arise from a DAD. Another finding indicates that the mechanism of defibrillation may differ depending on the duration of VF. The earliest postshock activation after the isoelectric period arises primarily in the working myocardium following VF of about 30 seconds, but arises primarily in Purkinje fibers after VF of 180 seconds.129 These differences in defibrillation after short- versus long-duration VF are probably related to the different characteristics of the activation wavefronts maintaining these short or long VFs.130-132 It has even been reported recently that endocardial ventricular activation is not reentrant but arises focally from Purkinje fibers in up to 30% of cases during long-duration VF133 (Fig. 2-17). This finding raises the startling possibility that to defibrillate

50

SECTION 1  Basic Principles of Device Therapy

64

74

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Figure 2-14  Example of postshock cycles after failed shock in pig. Defibrillation shock was of a strength near the defibrillation threshold (DFT), delivered from electrodes in the right ventricular apex and the superior vena cava. Recordings were made simultaneously from 504 electrodes distributed globally over the porcine ventricular epicardium. Electrode sites are indicated in gray on a polar projection, with the atrioventricular groove at the periphery and the left ventricular apex in the center. Anterior is at the bottom of the projection, and the left ventricle is to the right. Each panel shows in black the electrode sites at which an activation occurred at any time during each 10-msec interval. Numbers above the panels indicate the start of each 10-msec interval relative to the shock onset. Red arrows indicate the site of earliest recorded activation for each cycle. The first cycle appeared on the epicardium 64 msec after the shock at the anteroapical left ventricle. The second cycle (154 msec) arose on the epicardium in the same region as the first cycle and also propagated away in a focal pattern. The third (235 msec) and fourth (315 msec) cycles arose before the activation front from the previous cycle disappeared. (From Chattipakorn N, Fotuhi PC, Ideker RE: Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold. J Cardiovasc Electrophysiol 11:1014-1021, 2000.)



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

51

RV Posterior coronary vein

LAD

LV

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84

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A

B Figure 2-15  Similar activation patterns of postshock cycle 1 after failed (A) and successful (B) shocks. Maps from a pig heart are oriented as shown at top of figure; RV, right ventricle; LV, left ventricle; LAD, left anterior descending (coronary artery). Numbers above maps are times in milliseconds relative to defibrillation shock onset. Recording sites where action potential upstroke reached 50% of the action potential amplitude at any time during each 8-msec interval are black. Activation arose focally at the left ventricular apex where the shock electric field is weak and appeared 84 msec after the shock in A and 72 msec after the shock in B. Activation wavefronts propagated focally away from the apex toward the base in an organized pattern for both the failed and the successful shock episodes. (From Chattipakorn N, Banville I, Gray RA, Ideker RE: Mechanism of ventricular defibrillation for near-defibrillation threshold shocks: a whole-heart optical mapping study in swine. Circulation 104:1313-1319, 2001.)

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SECTION 1  Basic Principles of Device Therapy

Cai

A

100 msec

Vm Vm

Activation isochrone

Cai

C

–8 –4

0 msec

0

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4 8 (F–F)/F (%)

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60 msec

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Vm

Figure 2-16  Intracellular calcium (Cai) “sinkhole” and earliest postshock activation during unsuccessful shock in isolated rabbit heart. A, Optical signals from the site marked by an asterisk in B. The isoelectric window is the time between the time of the defibrillation shock (red line) and the time when the postshock Vm tracing crosses F (fluorescence strength, black line). B, Optical maps after failed shock (200 V), with time of the shock as time 0. C, Consecutive isochronal activation maps (left), isochronal repolarization map (middle), and Cai maps (right). Cai sinkholes (white arrows) are seen at the same site before the onset of the repetitive activations; Act, activation; Rep, repolarization. D, Optical tracings from the center (top two tracings) and edge (bottom two tracings) of the Cai sinkhole. Horizontal line segments on the tracings represent the levels of F. (From Hwang GS, Hayashi H, Tang L, et al: Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorff-perfused rabbit ventricles. Circulation 114:2595-2603, 2006.)



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

2

3

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5 6

7 8 9 10 11 12 13 14 15

Recordings

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53

RV apex

Activation times

aVR

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550 msec

Figure 2-17  Recordings and activation times for 15 cycles after ventricular fibrillation in dog. A, Soon after onset of VF; B, after 5 minutes of VF. Left ventricular endocardial basket recordings from 64 unipolar electrodes are shown at the top of each panel, with a right ventricular (RV) unipolar recording and ECG lead (aVR) below them. Below the ECG are the ventricular activation times recorded at the 64 basket electrodes during the same period, with each short vertical line representing an activation. At the bottom of each panel, the activations for all 64 electrodes are shown on a single line. The 15 cycles are numbered at the top of B. In A, endocardial activations are present throughout the cardiac cycles, consistent with reentry. In B, however, activation is highly synchronized with activation present during only a small part of the cardiac cycle, so that 14 large temporal gaps are present between the 15 cycles of activation in which no activations are present. This finding is inconsistent with reentry near the left ventricular endocardium. In both A and B, RV activation and ECG appear disorganized, as expected for VF. (From Robichaux RP et al: Periods of highly synchronous, non-reentrant endocardial activation cycles occur during long-duration ventricular fibrillation. J Cardiovasc Electrophysiol 21:1266-1273, 2010.)

long-duration VF, a shock must not only halt reentrant activation wavefronts, but also halt focal, possibly triggered, activity. Thus, although significant advances have been made in our understanding of the mechanisms of defibrillation, it is clear that there is still much more to be learned.

Acknowledgment This work was supported in part by National Institutes of Health grant HL-42760.

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Walcott GP, Walker RG, Krassowska W, et al: Choosing the optimum monophasic and biphasic waveforms for defibrillation. Pacing Clin Electrophysiol 17:789, 1994. 49. Blair HA: On the intensity-time relations for stimulation by electric currents. II. J Gen Physiol 15:731-755, 1932. 50. Lapicque L: L’Excitabilite en fonction du temps. Paris, 1926, Libraire J Gilbert, p 371. 51. Irnich W: The fundamental law of electrostimulation and its application to defibrillation. Pacing Clin Electrophysiol 13:14331447, 1990. 52. Sweeney RJ, Gill GM, Jones JL, Reid PR: Defibrillation using a high-frequency series of monophasic rectangular pulses: observations and model predictions. J Cardiovasc Electrophysiol 7:134143, 1996. 53. Walcott GP, Walker RG, Cates AW, et al: Choosing the optimal monophasic and biphasic waveforms for ventricular defibrillation. J Cardiovasc Electrophysiol 6:737-750, 1995. 54. Gold MR, Shorofsky SR: Strength-duration relationship for human transvenous defibrillation. Circulation 96:3517-3520, 1997. 55. Schuder JC, Stoeckle H, West JA,Kesar PY: Transthoracic ventricular defibrillation in the dog with truncated and untruncated exponential stimuli. IEEE Trans Biomed Eng 18:410-415, 1971. 56. Walcott GP, Melnick SB, Chapman FW, et al: Comparison of damped sinusoidal and truncated exponential waveforms for external defibrillation. J Am Coll Cardiol 27:237A, 1996. 57. Harbinson MT, Allen JD, Imam Z, et al: Rounded biphasic waveform reduces energy requirements for transvenous catheter cardioversion of atrial fibrillation and flutter. Pacing Clin Electrophysiol 20:226-229, 1997.

58. Hillsley RE, Walker RG, Swanson DK, et al: Is the second phase of a biphasic defibrillation waveform the defibrillating phase? Pacing Clin Electrophysiol 16:1401-1411, 1993. 59. Schuder JC, Rahmoeller GA, Stoeckle H: Transthoracic ventricular defibrillation with triangular and trapezoidal waveforms. Circ Res 19:689-694, 1966. 60. Denman RA, Umesan C, Martin PT, et al: Benefit of millisecond waveform durations for patients with high defibrillation thresholds. Heart Rhythm 3:536-541, 2006. 61. Keane D, Aweh N, Hynes B, et al: Achieving sufficient safety margins with fixed duration waveforms and the use of multiple time constants. Pacing Clin Electrophysiol 30:596-602, 2007. 62. Bardy GH, Marchlinski FE, Sharma AD, et al: Multicenter comparison of truncated biphasic shocks and standard damped sine wave monophasic shocks for transthoracic ventricular defibrillation. Transthoracic Investigators. Circulation 94:2507-2514, 1996. 63. Camacho MA, Lehr JL, Eisenberg SR: A three-dimensional finite element model of human transthoracic defibrillation: paddle placement and size. IEEE Trans Biomed Eng 42:572-578, 1995. 64. Lerman BB, Deale OC: Relation between transcardiac and transthoracic current during defibrillation in humans. Circ Res 67:1420-1426, 1990. 65. Karlon WJ, Eisenberg SR, Lehr JL: Effects of paddle placement and size on defibrillation current distribution: a threedimensional finite element model. IEEE Trans Biomed Eng 40:246-255, 1993. 66. Block M, Hammel D, Isburch F, et al: Results and realistic expectations with transvenous lead systems. Pacing Clin Electrophysiol 15:665-670, 1992. 67. Tang ASL, Wolf PD, Afework Y, et al: Three-dimensional potential gradient fields generated by intracardiac catheter and cutaneous patch electrodes. Circulation 85:1857-1864, 1992. 68. Tang ASL, Wolf PD, Claydown FJ III, et al: Measurement of defibrillation shock potential distributions and activation sequences of the heart in three-dimensions. Proc IEEE 76:11761186, 1988. 69. Chen PS, Wolf PD, Melnick SD, et al: Comparison of activation during ventricular fibrillation and following unsuccessful defibrillation shocks in open-chest dogs. Circ Res 66:1544-1560, 1990. 70. Chattipakorn N, Banville I, Gray RA, Ideker RE: Effects of shock strengths on ventricular defibrillation failure. Cardiovasc Res 61:39-44, 2004. 71. Shibata N, Chen PS, Dixon EG, et al: Epicardial activation after unsuccessful defibrillation shocks in dogs. Am J Physiol 255: 902-909, 1988. 72. Walcott GP, Chau WC, Ideker RE, et al: Early activation following shocks delivered in humans: the difference between transvenous and “active can” ICD systems. J Am Coll Cardiol 29:427A, 1997. 73. Crossley GH, Boyce K, Roelke M, et al: A prospective randomized trial of defibrillation thresholds from the right ventricular outflow tract and the right ventricular apex. Pacing Clin Electrophysiol 32:166-171, 2009. 74. Verma A, Kaplan AJ, Sarak B, et al: Incidence of very high defibrillation thresholds (DFT) and efficacy of subcutaneous (SQ) array insertion during implantable cardioverter defibrillator (ICD) implantation. J Interv Card Electrophysiol 29:127-133, 2010. 75. Kommuri NV, Kollepara SL, Saulitis E, et al: Azygos vein lead implantation for high defibrillation thresholds in implantable cardioverter defibrillator placement. Indian Pacing Electrophysiol J 10:49-54, 2010. 76. Walker RG, Walcott GP, Smith WM, Ideker IE: Sites of earliest activation following transvenous defibrillation. Circulation 90(pt 2):I-447, 1994. 77. Cates AW, Wolf PD, Hillsley RE, et al: The probability of defibrillation success and the incidence of postshock arrhythmia as a function of shock strength. Pacing Clin Electrophysiol 17:12081217, 1994. 78. Chapman FW, El-Abbaday TZ, Walcott GP, et al: Dysfunction following transthoracic defibrillation shocks in dogs. Pacing Clin Electrophysiol 20:1128, 1997. 79. Reddy RK, Gleva MJ, Gliner BE, et al: Biphasic transthoracic defibrillation causes fewer ECG ST-segment changes after shock. Ann Emerg Med 30:127-134, 1997. 80. DeBruin KA, Krassowska W: Electroporation and shockinduced transmembrane potential in a cardiac fiber during defibrillation strength shocks. Ann Biomed Eng 26:584-596, 1998. 81. Schuder JC, Gold JH, Stoeckle H, et al: Transthoracic ventricular defibrillation in the 100 kg calf with symmetrical one-cycle bidirectional rectangular wave stimuli. IEEE Trans Biomed Eng 30:415-422, 1983. 82. Yabe S, Smith DM, Duabert JP, et al: Conduction disturbances caused by high current density electric fields. Circ Res 66:11901203, 1990. 83. Jones JL, Jones RE: Decreased defibrillator-induced dysfunction with biphasic rectangular waveforms. Am J Physiol 247: H792H796, 1984. 84. Walcott GP, Knisley SB, Zhou X, et al: On the mechanism of ventricular defibrillation. Pacing Clin Electrophysiol 20:422-431, 1997. 85. Clark DM, Rogers JM, Ideker RE, Knisley SB: Intracardiac defibrillation-strength shocks produce large regions of hyperpolarization and depolarization. J Am Coll Cardiol 27:147A, 1996.

86. Zhou X, Wolf PD, Rollins DL, et al: Effects of monophasic and biphasic shocks on action potentials during ventricular fibrillation in dogs. Circ Res 73:325-334, 1993. 87. Daubert JP, Frazier DW, Wolf PD, et al: Response of relatively refractory canine myocardium to monophasic and biphasic shocks. Circulation 84:2522-2538, 1991. 88. Colavita PG, Wolf PD, Smith WM, et al: Determination of effects of internal countershock by direct cardiac recordings during normal rhythm. Am J Physiol 250: H736-H740, 1986. 89. Weidmann S: Electrical constants of trabecular muscle from mammalian heart. J Physiol 210:1041-1054, 1970. 90. Kléber AG, Riegger CB: Electrical constants of arterially perfused rabbit papillary muscle. J Physiol 385:307-324, 1987. 91. Krassowska W, Frazier DW, Pilkington TC, Ideker RE: Potential distribution in three-dimensional periodic myocardium. Part II. Application to extracellular stimulation. IEEE Trans Biomed Eng 37:267-284, 1990. 92. Krassowska W, Pilkington TC, Ideker RE: Potential distribution in three-dimensional periodic myocardium. Part I. Solution with two-scale asymptotic analysis. IEEE Trans Biomed Eng 37:252-266, 1990. 93. Plonsey R, Barr RC: Effect of microscopic and macroscopic discontinuities on the response of cardiac tissue to defibrillating (stimulating) currents. Med Biol Eng Comput 24:130-136, 1986. 94. White JB, Walcott GP, Pollard AE, Ideker RE: Myocardial discontinuities: a substrate for producing virtual electrodes that directly excite the myocardium by shocks. Circulation 97:17381745, 1998. 95. Tung L: A bidomain model for describing ischemic myocardial DC potentials, Cambridge, 1978, Massachusetts Institute of Technology. 96. Trayanova N: Discrete versus syncytial tissue behavior in a model of cardiac stimulation. II. Results of simulation. IEEE Trans Biomed Eng 43:1141-1150, 1996. 97. Trayanova N: Discrete versus syncytial tissue behavior in a model of cardiac stimulation. I. Mathematical formulation. IEEE Trans Biomed Eng 43:1129-1140, 1996. 98. Kieval RS, Spear JF, Moore EN: Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium. Circ Res 71:127-136, 1992. 99. Shaw RM, Rudy Y: Electrophysiologic effects of acute myocardial ischemia: a mechanistic investigation of action potential conduction and conduction failure. Circ Res 80:124-138, 1997. 100. Shaw RM, Rudy Y: Ionic mechanisms of propagation in cardiac tissue: roles of the sodium and L-type calcium currents during reduced excitability and decreased gap junction coupling. Circ Res 81:727-741, 1997. 101. Knisley SB, Blitchington TF, Hill BC, et al: Optical measurements of transmembrane potential changes during electric field stimulation of ventricular cells. Circ Res 72:255-270, 1993. 102. Windisch H, Ahammer H, Schaffer P, et al: Optical multisite monitoring of cell excitation phenomena in isolated cardiomyocytes. Pflugers Arch 430:508-518, 1995. 103. Wikswo JP, Lin SF, Abbas RA: Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation. Biophys J 69:2195-2210, 1995. 104. Zhou, X., Ideker RE, Blitchington TF, et al: Optical transmembrane potential measurements during defibrillation-strength shocks in perfused rabbit hearts. Circ Res 77:593-602, 1995. 105. Sommer JR, Scherer B: Geometry of cell and bundle appositions in cardiac muscle: light microscopy. Am J Physiol 248:H792H803, 1985. 106. Street AM, Plonsey R: Activation fronts elicited remote to the pacing site due to the presence of scar tissue. In Proc 18th Annu Int Conf IEEE Eng Med Biol Soc, Amsterdam, 1996, Piscataway, NJ, Institute of Electrical and Electronics Engineers. 107. Sharifov OF, Ideker RE, Fast VG: High-resolution optical mapping of intramural virtual electrodes in porcine left ventricular wall. Cardiovasc Res 64:448-456, 2004. 108. Clerc L: Directional differences of impulse spread in trabecular muscle from mammalian heart. J Physiol 255:335-346, 1976. 109. Knisley SB: Transmembrane voltage changes during unipolar stimulation of rabbit ventricle. Circ Res 77:1229-1239, 1995. 110. Efimov IR, Cheng YN, Van Wagoner DR, et al: Virtual electrodeinduced phase singularity: a basic mechanism of defibrillation failure. Circ Res 82:918-925, 1998. 111. Efimov IR, Cheng YN, Bierman M, et al: Transmembrane voltage changes produced by real and virtual electrodes during monophasic defibrillation shock delivered by an implantable electrode. J Cardiovasc Electrophysiol 8:1031-1045, 1997. 112. Iyer AN, Gray RA: An experimentalist’s approach to accurate localization of phase singularities during reentry. Ann Biomed Eng 29:47-59, 2001. 113. Knisley SB, Smith WM, Ideker RE: Effect of field stimulation on cellular repolarization in rabbit myocardium. Implications for reentry induction. Circ Res 70:707-715, 1992. 114. Chen PS, Wolf PD, Dixon EG, et al: Mechanism of ventricular vulnerability to single premature stimuli in open-chest dogs. Circ Res 62:1191-1209, 1988. 115. Frazier DW, Wolf PD, Wharton JM, et al: Stimulus-induced critical point: mechanism for electrical initiation of reentry in normal canine myocardium. J Clin Invest 83:1039-1052, 1989. 116. Winfree AT: When time breaks down: the three-dimensional dynamics of electrochemical waves and cardiac arrhythmias, Princeton, NJ, 1987, Princeton University Press. 117. Efimov IR, Cheng Y, Yamanouchi Y, et al: Direct evidence of the role of virtual electrode-induced phase singularity in success and



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

failure of defibrillation. J Cardiovasc Electrophysiol 11:861-868, 2000. 118. Chen PS, Shibata N, Dixon EG, et al: Activation during ventricular defibrillation in open-chest dogs: evidence of complete cessation and regeneration of ventricular fibrillation after unsuccessful shocks. J Clin Invest 77:810-823, 1986. 119. Chattipakorn N, Fotuhi PC, Ideker RE: Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold. J Cardiovasc Electrophysiol 11:1014-1021, 2000. 120. Chattipakorn N, Banville I, Gray RA, Ideker RE: Mechanism of ventricular defibrillation for near-defibrillation threshold shocks: a whole-heart optical mapping study in swine. Circulation 104:1313-1319, 2001. 121. Wang NC, Lee MH, Ohara T, et al: Optical mapping of ventricular defibrillation in isolated swine right ventricles: demonstration of a postshock isoelectric window after near-threshold defibrillation shocks. Circulation 104:227-233, 2001. 122. Chattipakorn N, Fotuhi PC, Chattipakorn SC, et al: Threedimensional mapping of earliest activation after near-threshold

ventricular defibrillation shocks. J Cardiovasc Electrophysiol 14:65-69, 2003. 123. Hwang GS, Hayashi H, Tang L, et al: Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorffperfused rabbit ventricles. Circulation 114:2595-2603, 2006. 124. Constantino J, Long Y, Ashihara T, Trayanova NA: Tunnel propagation following defibrillation with ICD shocks: hidden postshock activations in the left ventricular wall underlie isoelectric window. Heart Rhythm 7:953-961, 2010. 125. Hwang GS, Tang L, Joung B, et al: Superiority of biphasic over monophasic defibrillation shocks is attributable to less intracellular calcium transient heterogeneity. J Am Coll Cardiol 52:828835, 2008. 126. Chattipakorn N, Ideker RE: Delayed afterdepolarization inhibitor: a potential pharmacologic intervention to improve defibrillation efficacy. J Cardiovasc Electrophysiol 14:72-75, 2003. 127. Zheng X, Walcott GP, Smith WM, et al: Evidence that activation following failed defibrillation is not caused by triggered activity. J Cardiovasc Electrophysiol 16:1200-1205, 2005.

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128. Zheng X, Li L, Dosdall DJ, et al: Following long duration ventricular fibrillation, flunarizine greatly reduces the defibrillation threshold and the incidence of refibrillation. Circulation 120(Suppl 2):1481, 2009. 129. Dosdall DJ, Osorio J, Robichaux RP, et al: Purkinje activation precedes myocardial activation following defibrillation after long-duration ventricular fibrillation. Heart Rhythm 7:405-412, 2010. 130. Wiggers CJ: The mechanism and nature of ventricular fibrillation. Am Heart J 20:399-412, 1940. 131. Huang J, Rogers JM, Killingsworth CR, et al: Evolution of activation patterns during long-duration ventricular fibrillation in dogs. Am J Physiol Heart Circ Physiol 286:H1193-H1200, 2004. 132. Huizar JF, Warren MD, Shvedko AG, et al: Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart. Am J Physiol Heart Circ Physiol 293:H1617-H1628, 2007. 133. Robichaux RP, Dosdall DJ, Osorio J, et al: Periods of highly synchronous, non-reentrant endocardial activation cycles occur during long-duration ventricular fibrillation. J Cardiovasc Electrophysiol 21:1266-1273, 2010.

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3 

SECTION 1  Basic Principles of Device Therapy

Sensing and Detection CHARLES D. SWERDLOW  |  JEFFREY M. GILLBERG  |  PAUL KHAIRY

Sensing of cardiac depolarizations and detection of arrhythmias

control the electrical therapies of pacemakers and implantable cardioverter-defibrillators (ICDs). When a wavefront of depolarization passes the tip electrode of an intracardiac lead, a deflection in the continuous electrogram signal travels instantaneously up the lead wire to the pacemaker or ICD, where sensing electronics amplifies, filters, digitizes, and processes the signal. A sensed event occurs at the instant when the sensing system determines that an atrial or ventricular depolarization has occurred. Dual-chamber pacemakers and ICDs have separate sensing systems for the atrium and ventricle. Appropriate sensing results in one sensed event for each activation wavefront in the corresponding chamber. Failure to sense activation wavefronts results in undersensing, which can cause inappropriate pacing, failure to switch modes, or failure to detect a tachyarrhythmia. Undersensing occurs if the depolarization signal has insufficient amplitude or frequency content to be recognized as a sensed event, or if a blanking period disables the sensing amplifier at the time of the event. Oversensing occurs when nonphysiologic signals or physiologic signals that do not reflect local myocardial depolarization are sensed. Oversensing can cause inappropriate pacing inhibition, pacemaker tracking, or ICD therapy. Detection algorithms process sensed events to classify the atrial or ventricular rhythm. This classification is used to control beat-by-beat paced events, to change the pacing mode, to store data regarding tachyarrhythmias, and to terminate sustained tachyarrhythmias with antitachycardia pacing or shocks.

Electrograms SURFACE ELECTROCARDIOGRAM VS. INTRACARDIAC ELECTROGRAM An electrogram (EGM) is a graphic display of the potential difference between two points in space over time. During the upstroke of a myocardial action potential, the inside of the cell abruptly changes from its resting negative potential (with respect to the outside of the cell) to a neutral or slightly positive potential. After about 250 to 400 milliseconds (msec), the cell membrane is then repolarized, with the inside of the cell returning to its resting, negatively charged state. Figure 3-1 illustrates how an EGM is recorded between two electrodes in contact with the myocardium. The electrocardiogram (ECG) is recorded from two electrodes on the surface of the body at some distance from the heart. The typical amplitude of its QRS complex is about 1 millivolt (mV). The locations of the two electrodes determine the vectorial “viewpoint” from which the electrical activity of the entire heart is observed from the body surface. In contrast, the ventricular endocardial unipolar EGM typically is 5 to 20 mV in amplitude when recorded from a small electrode on the tip of a lead placed in direct contact with the apex of the right ventricle (Fig. 3-2). The second electrode needed to record this unipolar EGM is the pacemaker or ICD metal “can,” which is located some distance from the heart. The location of this distant second electrode, sometimes called the “indifferent electrode,” has a much smaller effect on the signal’s properties, although it may record noncardiac electric potentials (e.g., from pectoral muscle). The ECG records electrical activity from the entire heart, whereas the EGM records only local wavefronts of depolarization and repolarization. The EGM depends on

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the viability of approximately 1 or 2 cm3 of myocardium immediately under the tip electrode,1,2 as depicted in Figure 3-2. ELECTRODE SYSTEMS Figure 3-3 contrasts endocardial unipolar (tip-to-can), bipolar (tip-toring), and integrated bipolar (tip-to-coil) electrode systems, and Figure 3-4 shows representative examples. Epicardial electrode systems may be either unipolar (tip-to-can) or bipolar (tip-to-tip). These different electrode configurations have EGMs with similar R-wave amplitudes and slew rates, provided that the interelectrode spacing is at least 10 mm, as is true of almost all commercial pacemaker and defibrillator leads. Because they are more likely to oversense than bipolar EGMs, unipolar electrode systems are contraindicated for ICDs and are used infrequently for modern pacemakers. ICD integrated bipolar electrodes sense between the right ventricular tip electrode and right ventricular high-voltage coil, with sensing characteristics closer to the bipolar than the unipolar configuration. Compared with true bipolar electrodes, integrated ICD bipolar electrodes are more likely to oversense myopotentials and electromagnetic interference (EMI).3,4 In one study, oversensing occurred in 40% of patients with integrated bipolar sensing, compared with 8% of patients with true bipolar systems.4 AMPLITUDE, SLEW RATE, AND WAVESHAPE The largest and steepest deflection on the local EGM, called the intrinsic deflection, occurs when the wavefront of depolarization passes the small-tip electrode. The EGM amplitude traditionally is defined as the peak-to-peak amplitude of the intrinsic deflection (measured in mV), as shown in Figure 3-5. The duration of a ventricular EGM usually is less than that of the QRS of the surface ECG, because the EGM is a local signal. The amplitude of an atrial electrogram (AEGM) or ventricular electrogram (VEGM) is determined primarily by the excitable tissue near the tip electrode and therefore is usually similar for unipolar and bipolar signals. Typical amplitudes are 5 to 30 mV for VEGMs and 1.5 to 6 mV for AEGMs.1,2,5 The maximum slope of the intrinsic deflection is the slew rate, measured in volts per second, which represents the maximum rate of change of EGM voltage. Mathematically, it is the first derivative of the voltage, dV/dt, so it depends on both the amplitude and the duration of the EGM, and it provides a crude representation of the frequency content. The frequency content of ventricular and atrial EGMs is similar and in the range of 5 to 50 Hz. T waves and far-field R waves have lower frequency content, whereas most myopotentials and EMI have higher frequency content (Fig. 3-6). Typical values for slew rates are 2 to 3 V/sec for VEGMs and 1 to 2 V/sec for AEGMs.3,4 Usually, an EGM with acceptable amplitude also has an acceptable minimum slew rate (>1 V/sec for VEGMs, >0.3 V/sec for AEGMs). EGMs with very low amplitude will not be sensed, regardless of the slew rate. Increasing the size of the tip electrode in the range of 2 to 10 millimeters (mm) has minimal effect on atrial EGM amplitude but increases EGM duration (Fig. 3-7). For short ventricular bipolar interelectrode spacing of 5 mm or less, the R-wave amplitude decreases, because the difference between the two unipolar EGMs from each electrode causes cancellation in the net bipolar signal. The slew rate increases, because the time between arrival of the wavefront at the two electrodes decreases more than the EGM amplitude. When two electrodes are widely separated, as in early Y-adapted cardiac



3  Sensing and Detection

1

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resynchronization electrode systems, two distinct intrinsic deflections may be recorded on the EGM—one representing right ventricular (RV) activation and the other left ventricular (LV) activation. The interval between these deflections is determined by the conduction delay between the ventricles near the two electrodes. The waveshapes of EGMs are quite variable (Fig. 3-8), probably because geometry of the trabecular endocardium adjacent to the tip electrode is complex. In one study at pacemaker lead implantation, 58% of unipolar EGMs were biphasic, with an initial upstroke followed by a roughly equal downstroke; 30% were predominantly monophasic negative, and 12% were predominantly monophasic positive.1 The ventricular depolarization recorded on the atrial electrode is referred to as the far-field R wave (FFRW). Oversensing of the FFRW confounds interpretation of the atrial rhythm. The amplitude of the FFRW depends on the location of the atrial electrode. It is greatest near the septum, intermediate in the right atrial appendage, and least on

     

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E Figure 3-1  An electrogram (EGM) is recorded between two electrodes in contact with the myocardium. A, At rest, both electrodes record a similar charge, with no potential difference between them.  B and C, As a wavefront of depolarization moves under electrode 1, a difference in electrical charge is generated such that electrode  1 becomes electrically negative with respect to electrode 2. D, As the wavefront propagates under electrode 2, no potential difference between the two electrodes is recorded. E, The depolarization wavefront is followed by a wavefront of repolarization, during which a potential difference of opposite polarity is recorded. Because the EGM is determined by the instantaneous potential difference between the electrodes, the amplitude and shape of the recorded signal are determined by the direction from which the wavefront approaches the electrodes. For example, if a wavefront of depolarization reached both electrodes at the same time, there would be no potential difference between the electrodes, and an EGM would not be inscribed.

Time Figure 3-2  Concept drawing of spatial and temporal relationships for unipolar endocardial EGM. Upper panel, Anatomic drawing. Lower panel, EGM recorded from a small-surface-area electrode at the tip of a pacemaker or defibrillator lead that makes direct contact with the endocardium in the right ventricular (RV) apex. The second electrode required to record an EGM is not shown, because it is a distant and “indifferent” electrode, usually the metal can of the pulse generator, and its location is not important provided that it is a substantial distance from the tip electrode. During a ventricular depolarization, the depolarization wavefront propagates from the septum, around the RV apex, and up the RV free wall (arrows). When the wavefront of depolarization arrives at location 1, just as it approaches the electrode, the initial positive deflection of the EGM occurs, at time 1. When the wavefront passes closest to the tip electrode at location 2, the major negative deflection on the EGM occurs, labeled as time 2. As the wavefront recedes from the electrode at location 3, the final portion of the EGM is inscribed at time 3. This local EGM is not affected by the depolarization wavefront as it travels farther from the electrode. Therefore, the local EGM is shorter in duration than the surface electrocardiographic QRS complex.

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SECTION 1  Basic Principles of Device Therapy

pulse generator. Greater sensing safety margins are preferred for activefixation leads. The method of lead tip stabilization, active screw-in or passive tines, has had no significant effect on sensing characteristics in most studies.8,9 Steroid-eluting electrodes reduce chronic pacing thresholds substantially, but also have no significant effects on sensing.10-13 Metabolic, Ischemic, Aging, and Drug Effects RV-Coil

Ring Tip

Figure 3-3  The three practical endocardial electrode configurations used by most pacemakers and ICDs. The distant and indifferent or “can” electrode is not shown because it is out of the field of view. The unipolar configuration used in Figure 3-1 to explain EGM formation simply records the signal between the tip electrode and the can. The tip electrode can be an active-fixation screw or a small-surface-area tip electrode with various geometries. This unipolar configuration is subject to considerable noise and interference signals and is not suitable for ICDs. The bipolar configuration uses the Tip and Ring electrodes shown in this figure. The interelectrode spacing is typically 12 to 15 mm, and the ring electrode may or may not make contact with the endocardium. The integrated bipolar configuration uses the Tip and RV-Coil electrodes shown in the figure. EGMs recorded from bipolar and integrated bipolar configurations are very similar, and one less conductor is needed for the integrated bipolar configuration. The main disadvantages of the integrated bipolar configuration are susceptibility to diaphragmatic myopotentials, undesired atrial EGMs in small hearts, and slower postshock recovery times caused by electrode polarization. RV, Right ventricular.

the right atrial free wall. Even if the FFRW has comparable amplitude to the P wave, its slew rate usually is much lower. In one series, the mean slew rate was 1.2 V/sec for AEGMs and 0.13 V/sec for FFRWs.1 If an active-fixation, screw-in tip electrode is successfully attached to the myocardium, the acute VEGM has a current of injury, with an elevated ST segment (Fig. 3-9) that is usually greatly reduced within 10 minutes after electrode fixation. During this 10-minute period, the EGM amplitude and slew rate usually do not change despite changes in waveshape, but the pacing threshold decreases by an average of 40%.2 Acute to Chronic Changes and Fixation The amplitude and slew rate of intracardiac EGMs typically decline during the first several days to weeks after lead implantation and then increase to chronic values that are slightly lower than those measured at implantation.6 The initial decrease in EGM amplitude is caused by the inflammatory response and edema at the electrode-tissue interface. This gradually resolves and is followed by development of a small, inexcitable fibrotic zone surrounding the electrode tip (Fig. 3-10). This inflammation and fibrotic tissue effectively increases the distance between the surface of the electrode and excitable myocardium that generates the EGM signal. Although chronic EGM amplitudes usually are reduced by less than 10% compared with acute amplitudes, chronic slew rates are reduced by 30% to 40%.7 The acute reduction in EGM amplitude is often greater with activefixation leads than with passive fixation leads. Atrial undersensing can occur during the acute phase despite adequate EGM amplitudes at implantation. To account for these time-related changes in EGM amplitude, the filtered EGM recorded at lead implantation should be at least twice the sensitivity threshold that will be programmed in the

The effects of metabolic abnormalities and drugs on pacing thresholds are well described. Much less information is available concerning their effects on EGMs and sensing. Factors that reduce EGM amplitude, slow conduction velocity, or diminish slew rate may produce either oversensing or undersensing. By prolonging the intracardiac EGM duration beyond blanking periods, ischemia or antiarrhythmic drugs can produce double-counting of the QRS complex.14 Similarly, drugs that prolong the PR or QT interval beyond the refractory period may result in oversensing.15,16 Undersensing may result from reduction in EGM amplitude or slew rate after myocardial infarction at the electrode-tissue interface, from drug and electrolyte effects,15,16 or from progression of conduction system disease. Acute ischemia causes ST-segment changes that can be detected on VEGMs. Monitoring of EGM ST-segment shifts has been proposed as a method for monitoring ischemia for pacemakers and ICDs.17 The likelihood of recording abnormal AEGMs (defined as ≥100 msec in duration or having ≥8 fragmented deflections) correlates with age of the patient (r = 0.34; P < .0005).18 Exercise, Respiratory, and Postural Effects The effect of exercise on the AEGM amplitude and slew rate is variable. Some studies have reported statistically significant decreases in amplitude that average 10% to 20% but may reach 40% in some patients.19,20 Other studies did not find significant changes between rest and exercise.21,22 Decreases in AEGM amplitude were not caused by atrial rate alone or by beta blockade.23 VDD/R lead studies with “floating” atrial electrodes showed particularly large decreases with exercise.24,25 Decreases in AEGM amplitude with lead maturation support the programming of a large safety margin for sensing at implantation to offset effects of lead maturation. P-wave amplitude increases significantly during full inspiration, during full expiration, and with erect posture.22 Respiratory variation averaged 9.7% for unipolar AEGMs and 11.5% for bipolar AEGMs.25,26 The effect of respiration on VEGMs was less, especially with the unipolar configuration.26 Ventricular Electrograms during Premature Ventricular Complexes, Ventricular Tachycardia, and Ventricular Fibrillation Premature ventricular complexes (PVCs) may have lower-amplitude R waves than sinus-rhythm R waves, as shown in Figure 3-11, but the reverse may also be true. For monomorphic ventricular tachycardia (VT), mean amplitude decreased only slightly from values in sinus rhythm—14% for epicardial EGMs and 5% for endocardial EGMs.27 In contrast, EGM amplitudes during ventricular fibrillation (VF) decreased by 25% for epicardial and 41% for endocardial EGMs. More importantly, EGMs in VF often have low, highly variable, and rapidly changing amplitudes and slew rates. Figure 3-12 shows endocardial spontaneous VF EGMs from different patients, illustrating variability in intrinsic deflections, amplitudes, slew rates, and morphologies. In a study of induced VF reproducibility, 50% of the variability was caused by interpatient differences and the other 50% occurred among repeated episodes in the same patient.28 In another study, the VEGM amplitude in VF was 1 mV or less in at least one VF episode in 29% of patients.27 If VF lasts for minutes, the amplitude and slew rate of the EGMs decrease. Atrial Electrograms during Rhythms Other Than Sinus Atrial activation from ectopic sites or atrial arrhythmias can alter the amplitude, frequency content, slew rate, and morphology of the



3  Sensing and Detection

59

Figure 3-4  Ventricular electrocardiograms (ECGs) recorded from different electrode configurations in the same patient. The central panel shows a left anterior oblique radiograph of a cardiac resynchronization ICD system. Each of the four tracings shows surface ECG lead II, EGM markers, and one ventricular EGM during atrial pacing at a rate of 75 bpm. Top left, Far-field EGM recorded between the right ventricular (RV) coil electrode and the electrically active ICD housing (CAN). Lower left, Integrated bipolar EGM recorded between RV tip and RV coil electrodes. Lower right, True bipolar EGM recorded between the RV tip and ring electrodes. Top right, Left ventricular (LV) unipolar EGM recorded between the LV tip electrode and can. EGM scale is 0.5 mV/mm, except for the LV unipolar EGM, which has a scale of 2 mV/mm. The downward EGM ventricular sense (VS) markers correspond to the time at which the true bipolar RV tip-ring EGM crosses the sensing threshold. Because the “field of view” of this EGM is local, its duration is short. It occurs early in the QRS complex of this patient with left bundle branch block. The integrated bipolar tipcoil EGM has a peak-to-peak amplitude and slew rate similar to those of the true bipolar EGM. However, its field of view is larger due to the size of the RV coil, and therefore the T wave is larger. Low-amplitude atrial EGMs are visible because of the proximity of the coil to the tricuspid anulus. Both the RV coil-CAN and the LV unipolar EGM are widely spaced, between an intracardiac electrode and the extracardiac can. Their duration is closer to that of the QRS complex. The intrinsic deflection of the LV unipolar electrode is late in the QRS complex, corresponding to late activation of the lateral left ventricle. The greater amplitude of the LV unipolar EGM reflects the greater muscle mass of the left ventricle. EGMs recorded from the superior vena cava (SVC) coil and from the atrial bipole (right atrium, RA) are not shown. Radiograph and EGMs are from different patients. Radiograph is for illustrative purposes only.

AEGM. Retrograde atrial activation during ventricular pacing reduces AEGM amplitude and slew rate by up to 50%.29 These EGM changes are more pronounced in the high right atrium than in the right atrial appendage or low right atrium.30 The frequency content of the AEGM is not significantly altered by retrograde atrial activation.31 Analysis of EGM turning-point morphology or the first-differential coefficient of slew rate has been used to discriminate sinus EGMs from those recorded during retrograde and ectopic atrial activation in small groups of patients.32 Atrial EGMs during atrial fibrillation (AF) are characterized by extreme temporal and spatial variability. EGMs tend to be most organized in the trabeculated right atrial appendage and more disorganized in the smooth right atrium or coronary sinus.33-35 Thus electrode spacing and positioning of atrial leads influence EGM characteristics during AF36-38 and may cause inconsistent diagnosis of AF based on rate criteria. The amplitude of chronic, unipolar pacemaker EGMs was 40% less in AF than in sinus rhythm.39 A comparison of acute AEGM amplitudes recorded with temporary pacing catheters showed that the mean sinus-rhythm EGM amplitude decreased only slightly in atrial flutter but decreased by about 50% in AF.35 Antiarrhythmic drugs may also

interfere with sensing during AF by reducing atrial rate, median frequency, and EGM amplitude.40 SUBCUTANEOUS ELECTROCARDIOGRAPHY The subcutaneous ECG is similar to the surface ECG because the two subcutaneous electrodes are sufficiently distant from the heart that they record electrical activity from the entire heart. As with the surface ECG, the amplitude of subcutaneous ECG signals usually is 1 mV or less. Simultaneous recordings of subcutaneous ECG signals and surface ECG signals from electrodes placed directly over the subcutaneous locations have similar amplitude and signal-to-noise ratio.41 Practical implantation considerations usually limit the subcutaneous electrode separation distance to 4 to 8 cm, compared with the typical surface ECG limb lead electrode separation of 40 to 60 cm. The orientation of the two subcutaneous electrodes relative to the heart can affect the amplitude of the signal recorded.42 Mapping studies on the chest skin with 4-cm electrode spacing in the range used by implantable loop recorders (ILRs) show larger intrinsic QRS amplitudes of 0.5 ± 0.1 mV for vertical orientation in the left parasternal zone and for horizontal orientation near the apex of the heart.

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SECTION 1  Basic Principles of Device Therapy

Time (∆T)

chamber is turned off or “blanked” for a short blanking period (20-250 msec) after each spontaneous depolarization or pacing stimulus, to prevent a single depolarization resulting in multiple sensed events. In the refractory period that follows the blanking period, the sense amplifier remains enabled. Sensed events occurring in refractory periods do not alter pacemaker timing cycles but may be sensed for tachyarrhythmia detection algorithms. BLANKING AND REFRACTORY PERIODS

Amplitude Slew rate =

Voltage (mV) (∆V) in volts/sec (∆T)

SENSING

ATRIUM

VENTRICLE

Electrogram

>1.5-2.0 mV

>5-6 mV

Slew rate (V/sec)

>0.3

>1.0

Figure 3-5  Major clinical descriptors of electrogram. The peak-topeak amplitude of the EGM is the difference in voltage recorded between two electrodes and is measured in millivolts (mV). The slew rate is equal to the first derivative of the EGM (dV/dt) and is a measure of the sharpness of the EGM and therefore its frequency content. Slew rate is measured in volts per second (V/sec). Usually, the amplitude of the EGM should be greater than 1.5 to 2.0 mV in the atrium and at least 5 to 6 mV in the ventricle at the time of lead implantation, to ensure adequate sensing. The slew rate should be at least 0.3 V/sec in the atrium and at least 1 V/sec in the ventricle.

Subcutaneous ECGs are used to detect arrhythmias in ILRs, to obviate the need for surface ECG electrodes during follow-up of pacemakers and ICDs, and to detect VT/VF in an ICD without intravascular electrodes.

Sensing The methods and technology of sensing and detection in ICDs and pacemakers share many features, but there are two major differences. First, ICDs need reliable sensing and detection during VF, but pacemakers do not. Second, pacemakers may use unipolar or bipolar sensing, whereas ICDs always use bipolar sensing. GENERAL CONCEPTS Figure 3-13 shows the primary functional operations of sensing systems used by pacemakers and ICDs. The raw signal passes from the leads to the connector, through hermetic feedthroughs with highfrequency filters and high-voltage protection circuitry, before reaching the sensing amplifier. After the signal is amplified, a band-pass filter processes it to reduce T waves, myopotentials, and EMI (filtering). Then, it is rectified to nullify effects of signal polarity (rectification). Finally, it is compared with the sensing-threshold voltage. At the instant the processed signal exceeds the sensing-threshold voltage, a sensed event is declared to the timing circuits and indicated by a marker pulse on the programmer marker channel. The sense amplifier in the same

Signal amplitude (mV)

Voltage (∆V)

Blanking periods and refractory periods are used to prevent undesirable behavior caused by oversensing or double-counting of cardiac activity (Figs. 3-14 and 3-15). The specifications of blanking/refractory periods have substantial impact on ICD sensing and pacing functions (Fig. 3-16). Same-chamber blanking/refractory periods after sensed events reduce double-counting of intrinsic cardiac depolarizations that may result in escape pacing at a rate slower than the programmed lower rate in pacemakers or inappropriate detection of VF in ICDs. After paced events, the same-chamber blanking/refractory periods are typically longer and prevent oversensing of the pacing artifact and evoked response. The blanking/refractory periods in the ventricle after atrial sensed or paced events and in the atrium after ventricular sensed or paced events are called cross-chamber blanking/refractory periods. Cross-chamber blanking periods help to prevent oversensing of the pacing artifact after a paced event in the opposite chamber. The atrial blanking period after ventricular events, postventricular atrial blanking (PVAB), is designed to avoid oversensing of ventricular pacing stimuli and FFRWs. Longer postventricular atrial refractory periods (PVARPs) prevent retrogradely conducted atrial activation from resetting atrial timing cycles for dual-chamber pacing. Crosschamber blanking in the atrium after a ventricular event must be minimized in ICDs with tachyarrhythmia detection (ICDs or atrial therapy ICDs) to avoid undersensing the atrial rhythm, particularly during high ventricular rates. Long PVAB periods prevent reliable sensing of AF and atrial flutter/atrial tachycardia (AT). However, short PVAB periods may result in atrial sensing of FFRWs. NOT SENSED

SENSED

70 50 40 30 20 10

Amplifier threshold R Waves

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4

EMI

T Waves Far-field R wave

3 2

Muscle potentials

1 0.7 1

2

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20

50

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Frequency (Hz) Figure 3-6  Signal amplitude versus frequency. This plot shows the approximate characteristics of the P and R waves that pacemakers and ICDs are intended to sense and the approximate characteristics of  the electromagnetic interference (EMI, muscle potentials), T waves, and far-field R waves that they are intended not to sense. The sense amplifier’s filters are designed to sense signals that are above the U-shaped amplifier threshold curve and to reject signals that are below the curve. P waves and R waves have similar frequency characteristics, but usually R waves have higher dominant frequency than P waves. Muscle potentials usually have higher-frequency components than intracardiac signals. T waves and far-field R waves have lower frequencies. As shown, there are some overlaps in these amplitude-frequency characteristics that cause oversensing or undersensing in particular situations. The ellipses representing the amplitude-frequency characteristics in  this figure are conceptual and are not based on quantitative measurements.

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3  Sensing and Detection

Unipolar (mV)



200 ms

1.7 mV

2 mm Bipolar contact

32 msec 1.6 mV

10 mm Bipolar contact

Bipolar (mV)

1 mV

5 0 5

1

5

1.3 mV

Orthogonal contact

20 msec 0.8 mV

Orthogonal floating

20 msec Figure 3-7  Effects of electrode configurations on atrial endocardial electrogram. The EGMs were obtained from a single patient with two catheters placed simultaneously in the right atrial appendage. One catheter had 2-mm ring electrodes (top three tracings), and the other catheter had 1-mm orthogonal electrodes. The surface electrocardiogram tracing is shown at the top of the figure. Time and voltage amplitude scales are shown. For each electrode configuration (right), the corresponding EGM is shown (left), with the peak-to-peak amplitude and EGM duration labeled. “Contact” refers to electrodes in contact with the atrial tissue. “Floating” refers to noncontact electrodes in the atrial chamber. Note that greater ring electrode spacing, from 2 to 10 mm, prolongs EGM duration without altering the amplitude. The unipolar EGM shows a wider and diminished atrial EGM and a prominent far-field ventricular EGM as well. The orthogonal electrode configurations provide EGMs of lesser amplitude and shorter duration, compared with the ring electrodes.

Implantable cardioverter-defibrillators that require tachyarrhythmia detection typically have shorter blanking and refractory periods than standard pacemakers, so that short cardiac cycles can be sensed reliably. As shown in the bottom marker diagrams of Figure 3-16, blanking periods may be adaptively extended based on noise-sampling windows (30-60 msec) if suprathreshold activity (due to cardiac or extracardiac sources such as EMI) is identified on the EGM immediately after a sensed event. If noise is seen in consecutive windows after a sensed event, the blanking period is “retriggered” for that beat to avoid double-counting or continuous oversensing. This operation may result in paradoxical undersensing of the cardiac rhythm when more sensitive sensing levels are programmed if noise is oversensed.43,44 The duration of the total atrial refractory period (TARP), equal to the atrioventricular (AV) delay plus the PVARP, in DDD pacing modes limits atrial tracking of the atrium at high sinus rates without affecting atrial sensing, as shown in Figure 3-17. Because the AV delay of most dual-chamber pacemakers shortens in response to increasing atrial rates or sensor input, the TARP also shortens. Several manufacturers now offer dual-chamber pacemakers that shorten the PVARP with increasing atrial or sensor-indicated rates, further reducing the TARP during exercise. The result of these newer algorithms is that the programmed upper tracking rate can be safely increased while providing protection at lower heart rates from initiation of pacemaker-mediated tachycardia caused by retrograde conduction.

Unipolar (mV)

55 msec

Bipolar (mV)

1.0 mV

3

4

7

8

9

5

0 5

0

50 msec Unipolar contact

2

100 (ms)

5 0 5

6

5

10

0 5

0

100 (ms)

Figure 3-8  Similarities of unipolar and bipolar electrograms. Examples recorded from a lead placed in the right atrial appendage in 10 patients. Note that the amplitudes of unipolar and bipolar EGMs are similar for each patient. The waveshapes of unipolar and bipolar EGMs for a given patient may be quite similar (patient 3) or quite different (patient 8), although these differences can be attributed to the relative size of the major inflections. Some of these differences may depend on whether the ring electrode for the bipolar recording makes contact with the myocardium. On the whole, intrapatient differences between unipolar and bipolar recordings appear to be less than interpatient differences.

120 mV 110 mV

Acute

18.4 mV

10 minutes

14.4 mV

1 hour

13.1 mV

210 mV 220 mV 120 mV 110 mV

210 mV 220 mV 120 mV 110 mV

10 mV 20 mV Figure 3-9  Acute current of injury at implantation. Top panel, Highresolution recording shows marked ST-segment elevation, indicating the current of injury when an active fixation screw-in tip electrode is extended into the endocardium. Middle panel, After only 10 minutes, most of the ST-segment elevation in the signal has disappeared. Bottom panel, The EGM is not appreciably different at 1 hour after implantation.

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SECTION 1  Basic Principles of Device Therapy

SENSING THRESHOLDS IN PACEMAKERS

Approximate outline of lead body and helix Figure 3-10  Gross microscopic slide specimen shows myocardium remaining after removal of endocardial active-fixation screw lead. The large dotted line shows where the lead body was located, and the colored staining shows a thin, fibrotic sheath around the lead body. The approximate location of the helical screw-tip electrode is shown by  the solid coiled line. The oval shape (dotted line) shows the size of the fibrotic capsule that formed around the helical extended-tip electrode. Most of the tissue outside the dotted lines stained red, indicating that it was active myocardium capable of conducting depolarizations. The tip region of this electrode is similar to that of the tip electrode in Figure 3-1, so propagation of depolarization wavefronts must travel around the tip electrode, in tissue largely out of the field of view on the right side of this figure.

Sensing thresholds in most pacemakers are programmable to a constant value. Ventricular sensing channels in conventional pacemakers typically operate at sensing thresholds of 2.5 to 3.5 mV, about 10 times less sensitive than those in ICDs. Therefore, pacemakers may undersense VF. Atrial sensitivity thresholds are typically 0.3 to 0.6 mV, to allow sensing of small-amplitude atrial EGMs during AF and to improve the accuracy of AF diagnostics. Unipolar sensing thresholds typically are set higher (less sensitive) than bipolar sensing thresholds to reduce oversensing of far-field cardiac and extracardiac signals that can lead to inappropriate pacemaker inhibition or tracking. Newer pacemakers automatically adjust the sensitivity setting to adapt to changes in EGM amplitude over time. Typically, these functions operate to modify sensing thresholds based on a series of 10 to 20 ventricular beats. One such algorithm employs two simultaneous sensing levels: the programmed sensitivity (inner target) and a value twice the programmed value (outer target) (Fig. 3-18).45 Sensed EGMs exceeding both target values decrease the sensitivity. Signals exceeding only the inner target increase the sensitivity. In this manner, a 2 : 1 sensing margin is maintained. Rapid, automated sensitivity adjustments may be desired when EGM amplitudes can be expected to change over a brief period, such as beat-to-beat variations from respiration, body position changes, or fluctuating EGM morphologies during AF.46 Far-field R-wave oversensing can be minimized by (1) selecting an atrial lead with a closely spaced bipolar electrode pair (≤10 mm), (2) choosing an implantation location that yields an FFRW/P-wave ratio of less than 0.5,47 (3) titrating programmed sensitivity to reject FFRWs without undersensing P waves and low-amplitude AF, and (4) using PVAB.

CHART SPEED 25.0 mm/s ECG

0.2 mV/mm LEAD II

V EGM

1.0 mV/mm

Slew rate=dV/dt ∆V

P-P Amplitude

∆t

Marker channel

V S

V S

V S

V S

V S

V S

V S

V S

Figure 3-11  Surface electrocardiogram (ECG) lead II, bipolar right ventricular electrogram, and event markers with downward pulses that show when sensing occurred. The QRS amplitude on the ECG is about 1 mV, which is typical. The peak-to-peak amplitude of the sinus R waves is about 10 to 12 mV, which is also typical. The slew rate is the maximum slope (dV/dt) of the EGM intrinsic deflection; it is difficult to measure with a paper speed this slow. The two premature ventricular complexes (PVCs) (fourth and sixth) have different amplitudes and shapes on both the ECG and the EGM. The sinus beat in the center, between the two PVCs, has its main intrinsic deflection during the last part of the ECG QRS complex. The left edge of the sense marker indicates the instant that sensing by the ICD occurred. Therefore, EGM morphology and timing of the sense marker may not correspond to the start of the QRS on the ECG as electrocardiographers expect. Each R wave was sensed only once because sensing is blanked by the ICD for 120 msec after each ventricular sense (VS).



3  Sensing and Detection

63

1 mV

1 mV

1 mV

1 mV

1 mV

1 mV

1 mV

1 mV

1 sec

1 mV Figure 3-12  Variability in electrograms during spontaneous ventricular fibrillation (VF). Bipolar EGMs recorded during VF detection and charging by Medtronic Gem ICDs are shown for nine patients. The 1-mV calibration markers are the same except for the bottom tracing, where the calibration pulse is about three times larger, meaning that the ventricular EGM for this patient was three times smaller than for the other eight patients. Also note that rapid intrinsic deflections are visible on all tracings, although some substantial beat-to-beat variations in amplitude occurred. The abbreviated sense markers are shown at the bottom edge of each stored EGM strip. The sense amplifier blanking period was 120 msec, and the programmed sensitivity in each case was 0.3 mV, except in the sixth tracing from the top, which had 0.6 mV sensitivity. Note that there was slight VF undersensing on the bottom tracing when large EGMs were followed by smaller EGMs.

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SECTION 1  Basic Principles of Device Therapy

Time of sensed event Electrograms

Filter

Output

Voltage

100

0

Input

1

Rectifier

0

Frequency

To timing circuits

Threshold Voltage

Amplifier

Output

Electrodes and lead

Blanking period

Threshold

0

Input

Variable for Auto-gain control

Time

Variable for Auto-gain threshold

Figure 3-13  Functional block diagram for pacemaker or implantable cardioverter-defibrillator (ICD) sense amplifier. The EGM signal from the two implanted electrodes is first amplified for subsequent processing. Band-pass filtering reduces the amplitude of lower-frequency signals such as T waves and far-field R waves and higher-frequency signals such as myopotentials and electromagnetic interference. After band-pass filtering, the signal is rectified to make polarity unimportant. The thresholding operation compares the amplified, filtered, and rectified signals with the sensing threshold voltage. At the instant the processed signal exceeds the sensing threshold voltage, the sense amplifier is blanked (turned off) for 20 to 120 msec, so each depolarization is sensed only once, and a sensed event is declared to pacemaker or ICD timing circuits. For pacemakers, the programmed sensitivity controls the constant sensing threshold voltage. For ICDs, the amplifier gain may be controlled by the input EGM amplitude. The programmable sensing threshold for ICDs controls the high and low limits on the sensing threshold, which automatically adjusts on a beat-by-beat basis (see text discussion). In actual circuits, some functions (e.g., amplification, filtering) may be integrated.

VENTRICULAR SENSING IN VENTRICULAR ICDS The guiding design principle is that sensing of VF and polymorphic VT should be sufficiently reliable that clinically significant delays in detection do not occur. Although high sensitivity is required to ensure reliable sensing during VF, continuous high sensitivity results in oversensing of cardiac or extracardiac signals during regular rhythm, which may cause inappropriate detection of VT or VF. To minimize both undersensing during VF and oversensing during regular rhythms, ICDs use feedback mechanisms based on R-wave amplitude that adjust the sensing threshold dynamically. To maximize the likelihood of detecting VF, blanking periods are kept short. Automatic Adjustment of Sensitivity Adjustment of Sensitivity in Normal Rhythm.  All ICDs automatically adjust sensitivity in relation to the amplitude of each sensed R wave (Fig. 3-19). At the end of the blanking period after each sensed ventricular event, the sensing threshold is set to a high value. It then decreases with time until a minimum value is reached. Compared with a fixed sensing threshold, automatic adjustment of sensitivity increases the likelihood of sensing low-amplitude and varying EGMs, while minimizing the likelihood of T-wave oversensing. The methods of the different manufacturers for automatic adjustment of sensitivity perform similarly after small R waves but differently

after large R waves. Figure 3-20 shows that after large R waves, the Boston Scientific ICDs increase the sensing floor. In the Cognis/Teligen family, the sensing floor is set to one-eighth the amplitude of the measured R wave if that value is greater than the programmed sensitivity. This prevents T-wave oversensing in the setting of large R waves and reduces oversensing of low-amplitude noncardiac signals (e.g., diaphragmatic myopotentials, EMI). However, it may increase the risk of undersensing during rare episodes of VF with highly variable EGM amplitude.48 Postpacing Automatic Adjustment of Sensitivity.  After ventricular pacing, all ICDs set ventricular sensitivity to a highly sensitive value to prevent pacing during VF. The sensitivity threshold then decays to the programmed sensitivity level (Fig. 3-21). Thus ICDs are especially vulnerable to oversensing of low-amplitude signals late in diastole during pacing, when the amplifier sensitivity or gain is maximal. Clinically, the most important manifestation is the oversensing of diaphragmatic myopotentials.3

V P Figure 3-14  Loss of atrial sensing with apparent ventricular undersensing and ventricular pacing. In the second complex, an atrial pacing stimulus follows the P wave because of undersensing in the atrium. The atrial pacing stimulus occurs at the start of the ventricular QRS complex. The ventricular EGM is not sensed because of blanking in the ventricular sensing amplifier immediately after the atrial pacing stimulus. This sequence is repeated in the fourth, sixth, and eighth complexes. Atrial undersensing may lead to apparent ventricular undersensing because the ventricular blanking period does not permit sensing of electrical signals for 10 to 40 msec after an atrial output pulse.

V P

V P

V S

V P

V S

V P

Figure 3-15  Oversensing of T waves causing interruptions in VVI pacemaker timing. The surface electrocardiogram (top tracing) and pacemaker marker channel (bottom tracing) show ventricular oversensing of T waves. The first three complexes show ventricular pacing (VP) with capture. The pauses after the third and fourth complexes result from T-wave oversensing (VS), demonstrated by the marker channel.



3  Sensing and Detection

65

ECG AEGM VEGM

ICD

Marker channel AS 0 100

AS 30 100

120 VS AS

30 AP 200

200 VP

30

Adaptive (retriggerable) blanking periods

AS

AS 30 100

0 AP 200

200 VP

30 120 VS

200 VP

AP

AS

AP

Pacemaker VS

VP

VP

ICD same chamber: 200 ms postpace 120 ms post V sense 100 ms post A sense Cross-chamber: 30 ms postpace blank 0 ms postsense blank 310 ms postventricular refractory

VP

VS

Pacemaker same chamber: 63 ms postpace or postsense (retriggerable) 230 ms ventricular refractory period Cross-chamber: 180 ms postventricular atrial blanking 250-400 ms postventricular atrial refractory (auto) 20-45 ms postatrial pace ventricular blanking

Figure 3-16  Basic blanking and refractory periods for DDDR mode (Medtronic Marquis DR ICD and EnPulse DR pacemakers). The top tracings show the surface electrocardiogram (ECG), atrial electrogram (AEGM), and ventricular electrogram (VEGM) signals. The bottom two marker diagrams illustrate atrial or ventricular pacing (AP, VP), atrial or ventricular sensing (AS, VS), blanking periods (purple), and refractory periods (blue). Blanking periods in ICDs are usually of fixed duration, whereas same-chamber blanking in pacemakers is generally adaptive, with short (30-50 msec) blanking periods that “retrigger” when suprathreshold signals are present during the blanking period. Adaptive blanking periods can extend indefinitely, resulting in activation of noise-reversion asynchronous pacing. Note the considerably shorter blanking periods on the atrial channel in the ICD; this allows more accurate sensing of atrial depolarizations during high ventricular rates, which is critical for tachyarrhythmia detection and discrimination algorithms. Also note the lack of ventricular refractory periods in ICDs; this allows inhibition of pacing when high rates are sensed. Ventricular blanking periods in pacemakers may be shorter than in ICDs because of the approximately 10-fold less sensitive sensing threshold in pacemakers compared with ICDs.

Automatic Gain Control.  Early Ventritex ICDs (St. Jude Medical) used automatic step adjustments of gain as a primary means for avoiding T-wave oversensing and ensuring detection of low-amplitude VF EGMs. This resulted in sensing errors when EGM amplitude changed abruptly.49-51 In Boston Scientific ICDs before the Cognis/Teligen models, “slow” Automatic Gain Control adjusts the dynamic gain of the sensing amplifier slowly in response to temporal changes in R-wave amplitude. This ensures that the peak of the sensed R wave reaches about 75% of the amplifier gain, and that the sensing EGM is not truncated or “clipped.”

The minimum value of amplifier range is one eighth of the maximum value, so the minimum sensitivity decreases as R-wave amplitude increases. In Cognis/Teligen models, the range sense amplifier is sufficient (0 to 32 mV) that “slow” Automatic Gain Control is not used. In these Boston Scientific ICDs, “Automatic Gain Control” refers to automatic adjustment of sensitivity. In older Boston Scientific ICDs, “fast” Automatic Gain Control refers to automatic adjustment of sensitivity. Thus, whatever the name applied, automatic control of sensitivity, rather than gain, has become the primary method of beat-to-beat sensing adjustment in all ICDs. 2 seconds

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS AS

VP

AS

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS

VP

AS

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS AS

VP

AS

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS AS

VP

AS

AS

VP

Figure 3-17  Intracardiac marker channels. In a patient with a DDD pacemaker, channels identify atrial events within postventricular atrial refractory periods (PVARPs) that are sensed but not tracked. The surface electrocardiogram (top tracing) demonstrates ventricular pacing at the upper rate limit during atrial flutter. The atrial marker channel demonstrates atrial events that were sensed within PVARP (AS) and atrial events sensed outside PVARP (AS). After a ventricular pacing stimulus (VP), some atrial EGMs are not sensed, resulting in apparent EGM dropout because the atrium is blanked for a period after delivery of a VP. Only atrial signals recorded outside PVARP (AS) are tracked.

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SECTION 1  Basic Principles of Device Therapy

mV

mV

10 8 6 4 2 0 2 4 6 8 10 Increase Increase Increase Increase Increase Decrease Increase Decrease sensitivity sensitivity sensitivity sensitivity sensitivity sensitivity sensitivity sensitivity 2:1 safety Barely Converging on 2:1 safety Optimal sensing margin sensing margin for sensing (equilibrium around a achieved 2:1 safety margin) Outer target (1/2 sensitivity level) Inner target (programmed sensitivity level)

Figure 3-18  Autosensing algorithm to maintain a 2 : 1 sensing safety margin. See text for details. (From Castro A, Liebold A, Vincente J, et al: Evaluation of autosensing as an automatic means of maintaining a 2:1 sensing safety margin in an implanted pacemaker. Autosensing Investigation Team. Pacing Clin Electrophysiol 19:1708-1713, 1996.)

Ventricular Blanking Periods Ventricular blanking periods prevent ventricular oversensing of samechamber signals (R-wave double-counting) and cross-chamber signals (atrial pacing pulses and P waves) in regular rhythms. Because reliable sensing in VF requires minimizing blanking periods, blanking periods in ICDs are short and may occasionally be insufficient to prevent oversensing. Short Same-Chamber Blanking Periods and R-wave DoubleCounting.  In adults who are not taking antiarrhythmic drugs, interEGM intervals for filtered EGMs in VF vary from about 130 to 300 msec, with a peak near 200 msec (Fig. 3-22). Therefore, fixed or nominal blanking ICD periods after ventricular sensed events range from 120 to 135 msec. R-wave double-counting occurs if the duration of the sensing EGM exceeds the ventricular blanking period. Cross-Chamber Blanking Periods and Undersensing of VT/VF.  Under most conditions, ICDs apply only the minimum cross-chamber ventricular blanking required to prevent “crosstalk” resulting from an

Unfiltered R ventricular EGM

T

atrial pacing stimulus. During high-rate atrial or dual-chamber pacing, ventricular sensing may be restricted to short periods of the cardiac cycle because of the combined effects of ventricular blanking after ventricular events and cross-chamber ventricular blanking after atrial pacing. If a sufficient fraction of the cardiac cycle is blanked, systematic undersensing of VT or VF may occur. When pacing and blanking events occur at intervals that are multiples of a VT cycle length, ventricular complexes may be repeatedly undersensed, delaying or preventing detection.52-54 This occurs most often with rate-smoothing algorithms. “Sensing” Other Ventricular Electrograms Implantable cardioverter-defibrillator may use information derived from other VEGMs (shock-channel EGM, LV EGM in resynchronization systems) to enhance their functionality. The EGM from the shock channel (far-field EGM) is not used by transvenous ICDs for rate counting because bipolar or integrated bipolar EGMs are less susceptible to extracardiac signals. However, some manufacturers (Boston Scientific, Medtronic) use morphologic characteristics of far-field EGMs for discrimination of supraventricular tachycardia (SVT) from VT. Ventricular fibrillation

1 sec

Automatically adjusting sensing threshold

Filtered and rectified EGM 0.3 mV

Programmed sensitivity

Figure 3-19  Automatic adjustment of sensitivity. ICDs adjust sensitivity in relation to the amplitude of each sensed R wave. The goal of this feature is to permit sensing of low-amplitude and varying-amplitude EGMs while minimizing T-wave oversensing. The figure shows two sinus beats followed by the onset of ventricular fibrillation (VF). The upper panel shows the unfiltered ventricular EGM. The lower panel shows the corresponding filtered and rectified EGM. After each sensed ventricular event, the sensing threshold is set to a predetermined fraction of the R-wave amplitude. For large R waves, the initial sensing threshold may have a maximum value. The threshold then decreases with time until it reaches a minimum value equal to the programmed sensitivity, which is nominally about 0.3 mV. For sinus beats, the threshold is larger than the T waves, preventing oversensing. When VF begins, the smaller R waves keep the threshold at a lower value, which allows sensing of R waves that are even smaller than the T waves in sinus rhythm.



3  Sensing and Detection

Automatically adjusted sensitivity (mV)

10.0 Boston Scientific Medtronic St. Jude Threshold

9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 0

200

400

600

800

1000

Time (msec) Figure 3-20  Comparison of automatically adjusted sensitivity after sensed ventricular events for three manufacturers of ICDs after large (10 mV) R wave. The programmed sensing threshold is approximately 0.3 mV. After sensed ventricular events, Medtronic ICDs reset the sensing threshold to 8 to 10 times the programmed sensitivity, up to a maximum of 75% of the sensed R wave. The value of Auto-Adjusting Sensitivity then decays exponentially from the end of the (sense) blanking period, with a time constant of 450 msec, until it reaches the programmed (maximum) sensitivity. At the nominal sensitivity of 0.3 mV, there is little difference between the sensitivity curves of Medtronic ICDs after large and small spontaneous R waves. If the R wave is large, the entire Auto-Adjusting Sensitivity curve can be altered substantially by changing the programmed value of maximum sensitivity (see Fig. 3-19). At nominal settings, the St. Jude Threshold Start begins at 62.5% of the measured R wave for values between 3 and 6 mV. If the R-wave amplitude is greater than 6 mV or less than 3 mV, the Threshold Start is set to 62.5% of these values (3.75 mV and 1.875 mV, respectively). The sensing threshold remains constant for a Decay Delay period of 60 msec and then decays linearly with a slope of 3 mV/sec. Both the Threshold Start percent and the Decay Delay are programmable, over the range of 50% to 75% and 0 to 220 msec, respectively (see Fig. 3-21). Boston Scientific Cognis-Telegin ICDs set the starting threshold to 75% of sensed R waves with a maximum limit of 3/2 · Peak Running Average. Sensitivity then decays using digital steps, each seven-eighths the amplitude of the previous step. For sensed events, the duration of the first step is 65 msec, and the duration of subsequent steps is 35 msec. This results in a sensitivity of one-half the peak R wave in about 170 msec. (See text for further details.) After a paced ventricular event, all ICDs also adjust sensitivity dynamically, starting at the end of the (pace) blanking period, but the threshold starts at a more sensitive setting. (Modified from Swerdlow C, Friedman P: Advanced ICD troubleshooting. Part I. Pacing Clin Electrophysiol 28:1322-1346, 2005.)

Automatic analysis of the far-field EGM has also been proposed as a method to identify oversensing in ICDs resulting from lead fracture or sensing-lead connection problem. In one approach, the peak-peak far-field EGM amplitude is measured in a small window centered around each sensed event (on near-field channel) to discriminate rapid oversensing from true VT/VF. Oversensing is identified when sensed events on the near-field channel correspond to isoelectric periods on the far-field channel.55,56 In true VF, isoelectric periods are rare on the far-field channel (Fig. 3-23). Evaluating Sensing of Ventricular Fibrillation at Implantation Increasing interest in implanting ICDs without assessing defibrillation efficacy has focused attention on the extent to which adequacy of VF sensing can be determined from EGMs recorded in baseline rhythm.

67

Although the statistical correlation between R-wave amplitude in VF and baseline rhythm is weak,57,58 two studies reported that sensing of VF is adequate with nominal sensitivities near 0.3 mV if the baseline R wave is sufficiently large (≥5 mV or ≥7 mV).59 Rarely, clinically significant undersensing of VF or polymorphic VT may occur despite adequate sinus-rhythm R waves.48,60 In these cases, undersensing occurs because auto-adjusting sensitivity criteria respond inadequately to variations in R-wave amplitude, rather than consistently low-amplitude R waves. The reproducibility of this phenomenon is unknown, as is its predicted extent at implantation. Therefore, it is uncertain whether clinically appropriate testing at implantation can detect this infrequent cause of undersensing. During ICD implant with true bipolar sensing and current digital sensing amplifiers, clinically significant undersensing of VF is rare and unrelated to sinus-rhythm R-wave amplitude.61 Undersensing of spontaneous VT/VF in the VF zone is similarly rare. Reliable sensing of VF cannot be predicted from baseline EGMs if the baseline ventricular rhythm is paced. Sensitivity is programmed to a less sensitive value than nominal (e.g., to avoid T-wave oversensing), or patients have other implanted electronic ICDs, such as pacemakers, cardiac contractility modulation devices, or transcutaneous electrical nerve stimulation (TENS) units, that could cause device-device interactions. Postshock Sensing Postshock sensing is critical for redetection of VF after unsuccessful shocks and for accurate detection of episode termination. Electroporation, the process by which strong electric fields create microscopic holes in the cardiac cell membranes, has been proposed as the mechanism for postshock distortion of EGMs recorded from high-voltage electrodes.62 Because EGMs of dedicated bipolar sensing electrodes are minimally affected by shocks,63 they became standard for early epicardial ICDs. For transvenous ICDs, postshock sensing recovers more rapidly with true bipolar sensing configurations than with integrated bipolar sensing.64,65 This is a minor issue for current integrated bipolar leads with a pacing tip electrode–to–distal coil spacing of approximately 12 mm.66 ATRIAL SENSING IN DUAL-CHAMBER ICDS AND ATRIAL ICDS Accurate sensing of atrial EGMs is essential for accurate discrimination between VT/VF and rapidly conducted SVTs that satisfy ventricular rate criteria in dual- or triple-chamber ICDs. Rapid discrimination is essential to ensure prompt delivery of ventricular therapy while minimizing inappropriate shocks. Historically, some inappropriate detection of AT/AF has been considered an acceptable consequence of maintaining high sensitivity for detecting VT/VF. The atrial lead should be positioned at implantation to minimize FFRWs. Leads with an interelectrode spacing of 10 mm or less reduce oversensing of FFRWs. Atrial lead dislodgement, oversensing of FFRWs, or undersensing from low-amplitude AEGMs or atrial blanking periods can cause inaccurate identification of AEGMs. These errors in sensing may result in misclassification of VT as SVT, or vice versa. Postventricular Atrial Blanking and Rejection of Far-Field R Waves To prevent oversensing of FFRWs, older dual-chamber ICDs had fixed PVAB periods, similar to those in pacemakers (Fig. 3-24). With a fixed blanking period, the blanked proportion of the cardiac cycle increases with the ventricular rate. Atrial undersensing caused by PVAB causes underestimation of the atrial rate during rapidly conducted atrial flutter or AF, resulting in inappropriate detection of VT67 (Fig. 3-24, lower panel). Without PVAB, however, atrial oversensing of FFRWs could cause overestimation of the atrial rate during tachycardias with a 1 : 1 AV relationship.68 This may result in either inappropriate rejection of VT as SVT, if FFRWs are counted consistently as atrial EGMs, or inappropriate detection of SVT as VT, if FFRWs are counted inconsistently.69

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SECTION 1  Basic Principles of Device Therapy

Postpace

Postsense

Filtered and rectified EGM Postsensed maximum

8x

Postpaced maximum

4.5x

Programmed sensitivity

0.3mV

Postpace blanking Marker channel V Pace

V Pace

V Sense

V Pace

V Sense

Figure 3-21  Comparison of automatic adjustment of sensitivity after paced and sensed ventricular events. The filtered and rectified ventricular EGM, the corresponding sensing threshold, and ventricular (V) event markers are shown. Horizontal bars denote postpacing blanking periods. The blanking periods after paced events are longer than those after sensed events (250-350 vs. 120-140 msec), and the initial values of sensitivity are less. In this Medtronic ICD example, the initial sensing threshold after sensed events is 8 times the minimum programmed sensitivity of 0.3 mV, whereas the initial threshold after paced events is 4.5 times that value. The goal of a lower initial postpacing threshold is to prevent pacing into ventricular fibrillation. It compensates in part for the longer postpacing blanking period.

Medtronic ICDs also reject FFRWs algorithmically by identifying a specific pattern of atrial and ventricular events that fulfill specific criteria (Fig. 3-25). Intermittent sensing of FFRWs or frequent premature atrial events may disrupt this pattern, resulting in misclassification of a tachycardia. Therefore, it is preferable to reject FFRWs after sensed ventricular events by decreasing atrial sensitivity, if this can be done without undersensing of AF. Atrial sensitivity can be reduced to 0.45 mV with a low risk of undersensing AF. Less sensitive values should be programmed only if the likelihood of rapidly conducted AF is low. FFRW oversensing that occurs only after paced ventricular events (when auto-adjusting atrial sensitivity is maximal) does not cause inappropriate detection of SVT as VT, but it may cause inappropriate 100

Number of intervals

SENSING IN CARDIAC RESYNCHRONIZATION ICDS

Sensitivity = 0.3 mV n=772 Measured VF intervals n=786

80

60

40

20

0 0

100

200

300

400

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mode switching and can contribute to inappropriate detection of AF or atrial flutter. Medtronic ICDs (starting with Entrust) and Boston Scientific ICDs (starting with Vitality) may use brief atrial blanking or a period of reduced, automatically-adjusting sensitivity (or both) to reject FFRWs without preventing detection of AF (Fig. 3-26). St. Jude ICDs and Medtronic ICDs starting with Entrust provide programmable atrial blanking after sensed ventricular events to individualize the trade-off between oversensing of FFRWs and undersensing of AEGMs in AF. St. Jude ICDs also provide programmable atrial sensing Threshold Start and Decay Delay, corresponding to the same features in the ventricular channel.

600

Cycle length (msec) Figure 3-22  Sensed cycle lengths of human ventricular fibrillation (VF) EGMs by ICD sensing system compared with manual cyclelength measurements of same signals from many patients. Two histograms are superimposed. The red and orange vertical bars show the manually measured cycle lengths during VF (786 intervals); the blue bars show the intervals sensed by the ICD (772 intervals). Intervals of less than 120 msec, the blanking period, were not permitted. Note that there was some oversensing for intervals shorter than 180 msec, a slight amount of undersensing for intervals between 180 and 280 msec, and a small number of long intervals greater than 280 msec, which represent undersensing during VF. The peak in the histograms occurs at about 220 msec.

Left ventricular PVCs may activate the left ventricle but may not be sensed in the right ventricle before pacing is delivered. In this case, LV pacing could be delivered during the vulnerable period of the PVC. Boston Scientific cardiac resynchronization ICDs also sense in the left ventricle to reduce ventricular proarrhythmia by preventing pacing into the LV vulnerable period. The left ventricular protection period (LVPP) is a programmable interval (300-500 msec) following an LV event when the ICD will not pace in the left ventricle (Fig. 3-27). This prevents inadvertent delivery of an LV pacing pulse during the LV vulnerable period. The LVPP differs from other pacing refractory periods, which are designed to prevent inappropriate inhibition of pacing. In contrast, the left ventricular refractory period (LVRP), after a sensed or paced event on the LV lead, is a conventional refractory period. It prevents sensed events from causing inappropriate loss of cardiac resynchronization pacing following sensed events such as T-wave oversensing on the LV lead. The LVRP provides an interval following either an LV sense or an LV pace event (or leading ventricular pace event when LV offset is not programmed to zero), during which LV sensed events do not inhibit pacing. Use of a long LVRP shortens the LV sensing window. LVRP is available whenever LV sensing is enabled. Thus, LVRP minimizes unnecessary inhibition of resynchronization pacing while the LVPP minimizes the risk of LV pacing during the LV vulnerable periods.

Ventricular Oversensing: Recognition and Troubleshooting Oversensing is defined as sensing of unintended nonphysiologic signals or of physiologic signals that do not accurately reflect local depolarization. Nonphysiologic signals usually arise from extracardiac EMI (e.g.,



3  Sensing and Detection Lead noise

69

Ventricular fibrillation

Near-field EGM

Near-field EGM

Far-field EGM

Far-field EGM

Marker

Marker F 2 S2 1 7 0 0

F F S1 S 3 4 3 0 0

F S 3 7 0

F F F S1 S 1 S 3 3 5 1 0 0 0

F F F S 1 S1 S 3 4 0 0

4 5 0

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V S 2 3 0

V S 2 2 0

V F F F F S 1 S1 S1 S 2 S 2 0 7 5 5 0 0 0 0 0 0

V F F S 2 S1 S 3 2 0 0

4 7 0

VF Rx: Defib

Figure 3-23  Algorithm to discriminate pace-sense conductor failure of true bipolar ICD leads from ventricular fibrillation using far-field EGM (Medtronic Protecta ICDs, currently investigational). In pace-sense conductor failures, the far-field EGM has long isoelectric segments, which are not present in true VF. Stored EGM tracings during lead noise oversensing (left) and spontaneous VF (right) are shown; top tracings are the near-field (RVtip-RVring) EGM, middle tracings are the far-field EGM (RV coil-can), and the sensing markers are the lower tracing. Oversensing is identified by analyzing the peak-peak amplitudes of the far-field EGM in a 200-msec window centered at each of 12 sense markers (sensing derived from near-field EGM), as shown by the red arrows and boxes. Oversensing is identified when there are at least two far-field EGM analysis windows with isoelectric (3000 2000 1500 1000 800 600 400 300 3000 2000 1500 1000 800 600 400 300 2500 2000 1500 1000 800 600 400 300 3000 ohms

1000 ohms

08/31/ 06

D

11/09/ 06

01/18/ 07

03/29/ 07

>3000 2000 1500 1000 800 600 400 300 slowest VT τ Consider SVT specificity

terminate or discriminate 1 : 1 tachycardias by using simultaneous atrial and ventricular ATP.115 Single-Chamber Atrial Building Blocks The final four detection building blocks are the atrial correlates of the single-chamber ventricular building blocks: P-P interval (atrial cycle length), P-P regularity, P-P onset, and AEGM morphology. Their primary role is to identify the presence (or absence) of atrial tachyarrhythmias and to invoke (or inhibit) the application of single chamber ventricular building blocks such as interval stability and/or EGM morphology. To date, atrial EGM morphology has not been applied in ICDs to discriminate between antegrade and retrograde conduction. SVT-VT DISCRIMINATION IN SINGLE-CHAMBER ICDS R-R Interval Regularity Measures of R-R interval regularity usually are referred to as measures of R-R interval “stability” or “stability algorithms.” Technical details and optimal programmed values differ among manufacturers. Specific measures of R-R regularity interact with the method of counting R-R

intervals and the duration required for detection. Requiring consecutive R-R intervals or a higher number of intervals to fulfill the rate and regularity criteria improves rejection of AF but increases the risk that detection of VT will be delayed.107,108,116-120 Regularity criteria can reject AF with ventricular rates slower than 170 beats per minute (bpm) in the absence of antiarrhythmic drugs. At faster rates, these criteria cannot discriminate AF from VT reliably, because R-R intervals in AF are more regular;116-120 and the criteria may prevent detection of VT in the presence of amiodarone or type IC antiarrhythmic drugs.117,119 These drugs may cause regular VT to become irregular, or they may cause rapid polymorphic VT to slow from the VF zone, where discriminators do not apply, to the VT zone, where regularity discriminators do apply. R-R regularity may also be used to select the first VT therapy: ATP for regular VT and shock for irregular and presumed VF or polymorphic VT. Sudden Onset Measures of abruptness of onset of a tachycardia have high specificity for rejecting sinus tachycardia,116,118-120 but may prevent detection of VT that originates during SVT or VT that starts abruptly with an initial

Shock

AS

VF 265

AS 1713 VF 233

VF 255

VF 240

VF 243

VF 243

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AS 1713 VF 230 Detct Chrg

AS 855 VS 563

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AS 855

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VP 858

AS 855

AS 858 VF 858

VP 858

AS 855

AS 858 VP 858

VP 858 –– 23 Dvrt Chrg

70 min–1 70 min–1 Post–attempt EGM (10 sec max) Post–attempt Avs A Rate Post–attempt Avs V Rate

RV Tip-Coil

Attempt 1 Attempt Type Elapsed Time Therapy Delivered

Diverted Reconfirm 80.03 VF Shock 1

RA

–– 855

(AS) 858 VP 858

PVP+

Figure 3-53  Confirmation (“reconfirmation”) and aborted shock. Ventricular tachycardia (VT) in the ventricular fibrillation (VF) detection zone is detected and initiates capacitor charging (Chrg) before it terminates spontaneously. The noncommitted shock is diverted (Dvrt Chrg). AS, Atrial sensed event; VP, ventricular paced event.



89

3  Sensing and Detection Coil-Can

RV tip-ring

2 4 0

F D

V V V V V V V V S S S S S S S S 2 2 2 2 2 2 2 2 1 1 1 2 2 2 3 3 0 0 0 0 0 0 0 0 VF VF Rx 1 Defib

5 2 0

V S

4 5 0

V S

3 1 0

V S

4 9 0

V S

3 9 0

V S

3 8 0

V S

3 8 0

V S

3 8 0

V S

3 8 0

V S

3 9 0

V S

3 9 0

C V E S

3 9 0

C D 29.9J

7 2 0

V S

3 2 0

V S

Figure 3-54  Confirmation failure. Two ventricular EGMs and event markers are shown from a single-chamber ICD. The programmed ventricular tachycardia (VT) and ventricular fibrillation (VF) detection intervals are 380 and 320 msec, respectively. Detection of rapid VT as VF results in capacitor charging (VF Rx 1 Defib). After the charging cycle ends (CE), Medtronic ICDs deliver the shock (CD) if the ventricular cycle length after charging is less than the programmed VT interval + 60 msec. In St. Jude and Boston Scientific ICDs, shocks for VF are confirmed if the ventricular cycle length is less than the VT interval. RV, Right ventricular. (From Swerdlow CD, Friedman PA: Advanced ICD troubleshooting. Part II. Pacing Clin Electrophysiol 29:70-96, 2006.)

TABLE

3-1 

Tachyarrhythmia Detection Building Blocks

Tachyarrhythmia Detection Building Blocks Purpose/Information Single-Chamber Ventricular Building Blocks Identifies sustained high ventricular rates R-R interval + duration R-R regularity Discrimination of monomorphic VT (regular cycle lengths) from rapid AF (irregular cycle lengths) R-R onset

Identifies sudden ventricular rate changes

VEGM morphology

Abnormal VEGM morphology may indicate ventricular tachyarrhythmias Intervals after entrainment of VT by burst pacing are less variable than intervals after burst pacing during SVT

Burst ventricular pacing

Key Dual-Chamber Building Block Comparison of atrial vs. VT diagnosed if atrial rate is less than ventricular ventricular rate rate Dual-Chamber Building Blocks P-R dissociation P-R dissociation usually indicates VT P-R patterns/relationships

Consistent P-R patterns/relationships usually indicate SVT Chamber of acceleration Identifies whether tachycardia initiates in atrium or ventricle Atrial or ventricular pacing, Discrimination of 1 : 1 rhythms using ventricular response in opposite chamber response to atrial extrastimuli Single-Chamber Atrial Building Blocks P-P intervals Identifies high atrial rates P-P regularity Regular atrial rate indicates organized atrial activity P-P onset Identifies sudden atrial rate changes AEGM morphology

Identifies atrial tachyarrhythmias and/or retrograde conduction

Potential Weaknesses SVT with high ventricular rates that overlap with VT/VF rates May lose effectiveness as ventricular rates during AF increase; 2 : 1 atrial flutter has regular R-R intervals; may cause underdetection of VT with irregular R-R intervals Not specific for atrial or ventricular tachyarrhythmias; may miss VT arising during sinus tachycardia Confounded by conduction aberrancy or changes in “normal” VEGM morphology Sensitive to single interval measurement, potential detection time delay, and potential proarrhythmia

Confounded by atrial undersensing or far-field R-wave oversensing

AV reentrant tachycardia; VT with 1 : 1 retrograde conduction; AF that conducts rapidly with apparent P-R dissociation AV reentrant tachycardia and VT with 1 : 1 retrograde conduction A single oversensed/undersensed event may result in misclassification. Primarily aids diagnosis for 1 : 1 rhythms; concerns for VT detection delay and proarrhythmia High atrial rates may be present during true VT/VF. Minimal benefit for ventricular tachyarrhythmia characterization Not specific for atrial or ventricular tachyarrhythmias (e.g., VT with 1 : 1 retrograde association) Confounded by far-field R waves and changes in “normal” AEGM morphology

AEGM, Atrial electrogram; AF, atrial fibrillation; AV, atrioventricular; SVT, supraventricular tachycardia; VEGM, ventricular electrogram VF, ventricular fibrillation; VT, ventricular tachycardia.

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SECTION 1  Basic Principles of Device Therapy

rate below the VT detection limit. In the latter case, the ICD misclassifies the “onset” of the arrhythmia as the gradual acceleration of the VT rate across the VT rate boundary. This criterion does not prevent SVT with sudden onset from being treated inappropriately. Ventricular EGM Morphology Analysis of ventricular EGM morphology,114,120-123 alone or in combination with stability, probably provides the best single-chamber SVT-VT discrimination for initial detection of VT. The morphology building block is the key element of single-chamber algorithms and the central single-chamber component of dual-chamber algorithms with this feature. For this reason, a more detailed analysis is provided. VENTRICULAR EGM MORPHOLOGY FOR SVT-VT DISCRIMINATION General Electrogram morphology algorithms are the most complex and effective building blocks in single-chamber detection algorithms. All morphology algorithms share common steps (Fig. 3-55): (1) record a template EGM of baseline rhythm; (2) construct and store a quantitative representation of this template; (3) record EGMs from an unknown tachycardia; (4) time-align the template and tachycardia EGMs; (5) construct a quantitative, normalized representation of each tachycardia EGM; (6) compare the representation of each tachycardia EGM with that of the template to determine its degree of morphologic similarity; (7) classify each tachycardia EGM as a morphology match or nonmatch with the template; and (8) classify the tachycardia rhythm as VT or SVT based on the fraction of EGMs that match the template. Steps 3 through 8 are performed in real time. Morphology algorithms differ according to EGM source or sources, methods of filtering and alignment, and details of quantitative representations. The features of specific algorithms are described in Figure 3-56. Limitations of Morphology Algorithms The START study (SAFARI trial) of arrhythmias recorded at ICD implant reported individual differences for the performance of singlechamber discrimination algorithms based primarily on EGM morphology.124 Morphology algorithms share common failure modes for inappropriate detection of SVT as VT: (1) inaccurate template, (2) EGM truncation, (3) alignment errors, (4) oversensing of pectoral

Extracted features stored in ICD memory

Template EGM (baseline rhythm)

(1)

(4)

(2)

Compare features

Time align EGMs

Match % = 1 – Area of Difference Area of Template

Tachycardia Template

(2)

Extracted features calculated in real time

(4)

(3)

Tachycardia EGM Figure 3-55  General steps in all morphology algorithms. See text for details.

myopotentials, (5) rate-related aberrancy, (6) SVT soon after shocks, and (7) inappropriate classification of VT as SVT. Inaccurate Template.  The template may be inaccurate because the baseline EGM changed (e.g., postimplantation lead maturation, intermittent bundle branch block) or because the template was recorded from an abnormal rhythm (e.g., idioventricular or bigeminal PVCs). Accurate SVT-VT discrimination requires periodic automatic or manual template updates. Most modern ICDs include an automatic template updating feature, except for cardiac resynchronization ICDs, which are intended to pace the ventricles continuously. If automatic updates are not available, the morphology algorithm should be updated when the EGM becomes chronic. However, the template cannot be updated without intrinsic AV conduction. If software permits, the template match should be verified initially and during follow-up. Electrogram Truncation.  EGM truncation (“clipping”) occurs when the recorded EGM signal amplitude exceeds the range of the EGM amplifier so that the maximum or minimum portion of the EGM is clipped. This removes EGM features for analysis and alters the timing of the tallest peak, which can affect alignment. The amplitude scale in Medtronic and St. Jude ICDs should be adjusted so that the EGM used for morphology analysis is 25% to 75% of the dynamic range (Fig. 3-57). Alignment Errors.  Alignment errors prevent match between a tachycardia EGM and a morphologically similar stored EGM. Mechanisms depend on the method used for EGM alignment (Fig. 3-58). Accurate alignment in the St. Jude algorithm is sensitive to the value of the sensing threshold at the onset of the ventricular EGM, as determined by Automatic Sensitivity Control. If a template EGM is acquired at the most sensitive setting of Automatic Sensitivity Control (either because of a slow sinus rate or after a ventricular paced beat), a low-amplitude peak at the onset of the ventricular EGM may be used for alignment. During tachycardia, the next R wave may occur before Automatic Sensitivity Control reaches its sensitive value. In this case, the lowamplitude peak at the onset of the ventricular EGM may not be used for alignment. If identical template and tachycardia EGMs are then compared, their representations in the morphology algorithm will not match. Usually, they are assigned morphology match scores of 0% (see Fig. 3-58). In patients who have dual-chamber ICDs and intact AV conduction, the most reliable template is acquired or verified during atrial pacing at a rate close to the VT rate. In single-chamber ICDs, options may include acquiring or verifying the template during exercise testing and altering the minimum sensitivity, Threshold Start, or Threshold Delay. If a template is acquired during atrial pacing or exercise testing, automatic template updating should be disabled to prevent overwriting the template with one acquired in baseline rhythm. Medtronic ICDs align EGMs based on their tallest (positive or negative) peaks. If an EGM has two peaks of near-equal amplitude, or if such peaks are caused artificially by truncation of large EGMs that exceed the programmed dynamic range, minor variations in their relative amplitudes may result in an alignment error.120 An alternative EGM source should be selected. The Boston Scientific morphology algorithm (Rhythm ID) simultaneously collects data from two different channels: the local bipolar rate-sense EGM and shock EGM.125,126 It considers the vector of depolarization wavefront (with shock EGM as the reference), the timing of the peak signal recorded on the rate-sense EGM, and alignment of eight characteristic points of the shock EGM. A correlation equation aligns peaks on the rate-sense EGM for each QRS complex of the unknown rhythm with the rate-sense EGM peak of the sinus template, then compares the eight captured points with the template. Oversensing of Pectoral Myopotentials.  In Medtronic ICDs, oversensing of pectoral myopotentials may prevent an SVT from matching the sinus template if the RV coil-to-can EGM is used for morphology analysis and the R-wave amplitude is small. The effect of myopotentials



3  Sensing and Detection

91

100 Shock

50 0 Template

50 B

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Tachycardia EGM

A

–

B –

= A’

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60 40 20 0 −20 −40

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Wavelet transform

mV

Digitized electrogram (x[n]) 0

200 msec Smallest amplitude wavelets

C

− 0 +

0

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Figure 3-56  Specific morphology algorithms. A, St. Jude MD algorithm. The positive and negative deflections in the sensing EGM are normalized and modeled as a series of three polygons (A, B, and C in the template EGM; A’, B’, and C’ in the tachycardia EGM). The normalized areas of these polygons are then computed. Each tachycardia EGM is compared with the template EGM in three steps. First, the difference in area of corresponding polygons is computed. Second, the absolute values of these differences are summed. Third, a match score is constructed to be inversely proportional to the sum of these differences. If a programmable number (= 4) of 8 complexes in a sliding window exceed the programmable threshold (nominally 60%), the rhythm is classified as supraventricular tachycardia (SVT). If not, it is classified as ventricular tachycardia (VT). B, Boston Scientific Vector Timing and Correlation (VTC) algorithm. This algorithm aligns shocking EGMs of the tachycardia and template based on the peak of the rate-sensing EGM. This method takes advantage of spatiotemporal differences between activation sequences in VT and baseline rhythm that cannot be detected from a single EGM. In this example, the peak of the shock EGM has similar timing to the peak of the rate-sensing EGM in sinus rhythm, but much later timing in VT. The amplitude of the shocking EGM (upper panel) is computed at each of 8 points selected on the basis of their timing relative to the peak of the sensing EGM (lower panel) and extracted as an eight-element “feature set,” corresponding to an eightdimensional vector. Feature sets of each tachycardia EGM are compared with the template EGM by computing the product-moment correlation coefficient between the two feature sets. This value, named the feature correlation coefficient (FCC), is a measure of mean spatiotemporal difference in ventricular activation between tachycardia and baseline rhythm. A threshold value for the feature correlation coefficient was selected to optimize SVT-VT discrimination on a test data set. This value is neither published nor programmable. If at least 3 of 10 complexes in a sliding window exceed the threshold, the rhythm is classified as SVT; if not, it is classified as VT. C, Medtronic Wavelet algorithm. The algorithm expresses the morphology of ventricular EGMs using the wavelet-transform. Wavelets are functions of constant shape and limited time duration.* They form the basis of a mathematical transformation that represents signals efficiently if they are both highly localized in time and preceded and followed by isoelectric intervals. Wavelets are therefore well suited for representing transient biomedical signals such as ventricular EGMs. The algorithm compares the morphology of ventricular EGMs during a tachycardia with a template recorded during baseline rhythm. This comparison is expressed as a percent-match score that describes the degree of morphologic similarity of the baseline and tachycardia EGMs using a programmable source. In general, the EGM recorded between right ventricular and superior vena cava coils is preferred as a default. This signal combines far-field sensitivity to morphology differences between VT and SVT with resistance to pectoral myopotentials. The algorithm begins processing when a tachycardia fulfills the programmed rate criterion for detection of VT and 8 beats remain to fulfill the programmed duration criterion for detection of VT. Percentmatch scores are calculated for each of the last 8 beats before detection. Beats with match scores less than a programmable threshold (nominally 70%) are classified as ventricular. Nominally, a tachycardia is classified as VT if 6 or more of the 8 analyzed EGMs are classified as ventricular. Otherwise, it is classified initially as SVT. If the tachycardia is classified as SVT, the algorithm is applied to each successive 8-beat sliding window until the rate criterion for VT is no longer fulfilled. (*Meyer Y: Wavelets: algorithms and applications. Philadelphia, 1993, Society for Industrial and Applied Mathematics.)

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SECTION 1  Basic Principles of Device Therapy

Range 9.8 mV

Range 14.4 mV

A

T S

5 9 0

V S

6 5 0

V S

4 5 0

No match 64%

V S

5 2 0

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3 4 0

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T T 3 S 3 S 2 1 0 0

No match 64%

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3 2 0

No match 61%

T S 3 3 0

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3 4 0

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T 3 S 3 4 4 0 0

T S 3 3 0

T S

3 7 0

T S

Figure 3-57  Electrogram truncation as source of error for morphology algorithms. A, St. Jude MD template EGM is truncated (arrow) with an amplifier range of 9.8 mV. Truncation was corrected by increasing the range to 14.4 mV. Inconsistent truncation may prevent supraventricular tachycardia (SVT) morphology from matching the template. B, Medtronic Wavelet algorithm. EGMs in rapidly conducted atrial fibrillation exceed the maximum amplitude range of 8 mV, resulting in varying degrees of truncation (“clipping”) of the right ventricular (RV) coil-to-can + superior vena cava (SVC) signal compared with the template. Inappropriate detection of ventricular tachycardia (VT) occurs at right. Complexes below show the last eight EGMs before detection at higher resolution. These tachycardia EGMs are clipped (arrow) so that the peaks are cut off. The rhythm is classified as VT because six of the last eight EGMs have less than 70% match. This problem was corrected by expanding the EGM scale ±16 mV AS, Atrial sensed event; VP, ventricular paced event.

T 3 D 3 6 0 0 VT 0

No match 64%

4 mV 20 ms QRS Template

No match 67%

Match 76%

No match 61%

Match 76%

B

SVT

X

SINUS

X

X

T

386 397

S

T

100

0

0

0

417

382

397

401

394

858 862 A 394

0

100 866

862 A

R

862 A

R 233

629 R

100 866

229 R R Sensitivity

S

R 229

633

637

R

10

Figure 3-58  Alignment error in morphology algorithm. Interaction of Automatic Sensitivity Control and morphology analysis in St. Jude MD algorithm. Left panel, Stored EGM of supraventricular tachycardia (SVT) inappropriately detected as ventricular tachycardia (VT). Right panel, Programmer strip of validated template in sinus rhythm. Despite identical ventricular EGMs, morphology match scores are 0% in SVT and 100% in sinus rhythm. Slanted line denotes slope of Automatic Sensitivity Control. In sinus rhythm, Automatic Sensitivity Control reaches minimum value before the next ventricular EGM, so that the small peak at onset of EGM (arrows) is used for alignment. In SVT, Automatic Sensitivity Control does not reach minimum, and the small peak is not used for alignment.



3  Sensing and Detection

93

degrees of aberration often distort the terminal portion of the EGM sufficiently that the percent match is less than the nominal threshold. In St. Jude ICDs, reducing the fraction of EGMs required to exceed the match threshold from 5 of 8 beats to 3 or 4 of 8 beats may reduce this problem without compromising detection of monomorphic VT. Reducing the match percent required to exceed the match threshold may also prevent misclassification of aberrantly conducted SVT as VT, but it results in a greater chance of misclassifying monomorphic VT as SVT than does reducing the fraction of EGMs.

on match percent can be tested by pectoral muscle exercise. Select an alternative EGM source (e.g., distal coil to proximal coil) to prevent such oversensing. Pectoral myopotentials also pose a source of error in Boston Scientific ICDs, which necessarily incorporate the high-voltage EGM in morphology analysis. Oversensing of pectoral myopotentials is not a problem for St. Jude ICDs, which use near-field EGMs for morphology analysis. Rate-Related Aberrancy.  If complete bundle branch aberrancy occurs reproducibly, the template may be recorded during rapid atrial pacing (Fig. 3-59). However, subtle and varying aberrancy can confound templates acquired during baseline rhythm (Fig. 3-60). If a template is acquired at a fast rate, automatic template updating should be deactivated to prevent subsequent auto-acquisition of a slow, baseline template without aberrancy. During rapidly conducted AF, subtle

Supraventricular Tachycardia Soon after Shock.  After a shock, ICD detection algorithms reclassify the rhythm as “sinus” and revert to their initial detection mode within a few seconds, but postshock distortion of EGM morphology may persist for 30 seconds to several minutes.60,120 No SVT-VT discrimination algorithm relies on EGM morphology

V.C.6 TEMPLATE IN LBBB WITH ATRIAL PACING A. Capture confirmed: 1.0 V @ 0.5 ms 1.0 V

A. Capture lost: 0.75 V @ 0.5 ms 0.75 V

Return: 3.5 V

ECG

x

x

x

x

x

x

34

40

37

37

40

31

S 664

664 660

A

664 664

664

A R

A R

297

297 383

664 668

A R 297 367

664

289

A

A

A

R 297

367

664 664

A

R

281 367

664

S 100

100

1001

A

P

R

R

R

281 367

242 383

751

RA

RV

ECG

x 100 750 750 A R 289 461

RA

100 750 750 A R 881 469

x 40 750

A 281

R

R 469

100 750 750 A R 281 469

100 750 754 A R 281 469

100 750 750 A R 289 461

100 750 750 A R 289 461

100 750 750 A R 289 461

100 750 746 A R 289 461

100 750 750 A R 889 461

RV

Baseline

Atrial pacing LBBB

Press here for Active Template Scoring

Now Scoring

Figure 3-59  Left bundle branch aberrancy error in morphology algorithm. Programmer strips show electrocardiogram (ECG), event markers, right atrial EGM, and right ventricular true bipolar EGM. Top panel, Measurement of atrial pacing threshold. Captured beats are conducted with rate-related left bundle branch aberrancy resulting in failure of morphology to match template collected in sinus rhythm. The last two ventricular EGMs at the slower sinus rate show 100% template match. A new template was acquired during atrial pacing. Middle panel, Near 100% morphology match to new template during conduction with left bundle branch aberrancy. Bottom panel, EGM morphology templates recorded during baseline sinus rhythm (left) and atrial pacing (right). LBBB, Left bundle branch block; RA, right atrium; RV, right ventricle.

94

SECTION 1  Basic Principles of Device Therapy

DD

RA

Trigger X S T T T T T T T T T T T T T T T T ATP ATP ATP ATP ATP 46 44 36 39 38 51 37 49 39 35 57 43 24 28 50 D= 355 348 355 352 348 352 355 348 348 352 348 348 352 348 348 343 343 343 359 343 355 352 352 352 352 352 352 352 348 352 352 348 348 348 348 348 X

R

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

R

ATP ATP ATP ATP ATP

R

RV

* R

* R

* R

* R

* R

* R

* R

* R

* R

* R

* R

* R

H V

* R

R R R D 332 340 332 336 336 332 340 336 336 336 336 340 336 336 340 340 336 336 336 332 336 336 336 336 336 336 336 340 336 336 344 340 R

R

R

R

R

R

R

R

R

R

R

ECG

R

R

R

R

X S

X S

0

S 100

703 543 P

R

156

RA

RV

S 0

S 100

527 P

P R

R

520

559 P

S 100

754 P

R 156

673

S 0

100

668

828

156 689

X

684

843 P

R

309 301 250 367 297

R

V

R

R

R

ECG

X 100

S 649V

485

660 P

P

P

R

R

R

70

156

156

698

500

X

X

X

X

X

X

X

61 62 0 21 38 51 34 0 0 52 398 398 398 398 398 398 398 398 398 398 402 406 402 402 402 406 402 402 395 398 A A A A A A A A A A R

R 243

R 243

R 273

R 273

R 281

R 297

R 289

303

R R R 297 297

528

RA

RV

Figure 3-60  Error in morphology algorithm caused by subtle rate-related aberrancy. Top panel and middle panel, Dual-chamber stored EGM from inappropriately treated sinus tachycardia. Right atrial (RA) EGMs, event markers, and true bipolar right ventricular (RV) EGMs are shown. Values immediately below event markers, corresponding to EGMs in ventricular tachycardia (VT) zone (labeled “T”), indicate the percent match between EGM morphology in VT and sinus morphology (seen in lower left panel). Corresponding “X” labels above event markers indicate that the morphology algorithm classifies the beat as VT because the match is less than 60%. Burst antitachycardia pacing (ATP) is delivered at the right of the first panel. Dotted arrow indicates that panels are not continuous. After several trials of ATP (not shown), a shock is delivered toward the end of the second panel (HV). “Trigger” at right of upper panel indicates (inappropriate) detection of VT. “D =” at right of upper panel indicates that the atrial rate is equal to the ventricular rate. S denotes intervals in the sinus zone above the VT detection interval of 360 msec. Time line is in seconds. Bottom panels show real-time programmer strips. Bottom left panel, 100% template match in sinus rhythm (arrows) and 0% match on premature ventricular complexes (PVCs). However, the bottom right panel, recorded during atrial pacing at a cycle length of 400 msec, shows only two EGMs with adequate match (check marks, arrows). Note that the surface electrocardiogram (ECG) does not show identifiable aberrancy despite sufficient changes in EGM to prevent template match.



3  Sensing and Detection

after shocks until the arrhythmia episode terminates. However, algorithms revert to their initial detection mode within a few seconds after a shock. If postshock SVT starts after the rhythm has been classified as sinus but before postshock EGM distortion dissipates, any morphology algorithm may misclassify SVT as VT.120 Therefore, distortion of the EGM after a shock could result in a repetitive sequence of inappropriate classification of SVT as VT, inappropriate shocks for SVT, and perpetuation of postshock EGM changes in SVT by each successive shock.

95

about whether comparable features are required for Medtronic and Boston Scientific algorithms. SVT-VT DISCRIMINATION IN DUAL-CHAMBER AND CARDIAC RESYNCHRONIZATION ICDS The integration of dual-chamber building blocks into detection algorithms may be considered in terms of the relative rates of the atrium and ventricle (Fig. 3-62). Operation for Atrial Rate Less Than Ventricular Rate

Inappropriate Classification of Ventricular Tachycardia as Supraventricular Tachycardia.  The St. Jude morphology algorithm, which analyzes only the rate-sensing electrode, continuously misclassifies up to 6% of VTs as SVT (Fig. 3-61). However, if it is restricted to tachycardias (with ventricular rate ≤ atrial rate in dual-chamber ICDs), only 2% of VTs are misclassified.114 The Medtronic morphology algorithm, which usually analyzes high-voltage EGMs, misclassifies about 1% of VTs as SVT.127 If misclassification occurs, an alternative EGM source may provide adequate discrimination. Limited data indicate that the corresponding error rate for the Boston Scientific algorithm is comparable or lower. When the St. Jude morphology algorithm is used in a single-chamber ICD, the sustained-duration time-out (Maximum Time to Diagnosis, Section V.F) should be programmed unless the algorithm is known to classify all clinical VTs correctly. Opinions differ

Dual-chamber detection algorithms revert to single-chamber operation when the atrial rate is slower than the ventricular rate and generally do not apply any single-chamber discriminators. Operation for Atrial Rate Equal to Ventricular Rate The vast majority of tachycardias with 1 : 1 AV relationship are SVT, primarily sinus tachycardia. VT with 1 : 1 VA conduction accounts for less than 10% of VTs detected by ICDs. The building blocks used by each manufacturer for distinguishing 1 : 1 AV conduction of SVT from 1 : 1 VA conduction are summarized in Table 3-2. A dual-chamber onset rule that evaluates both P-R and R-R interval onset improves specificity of R-R interval onset-type building blocks for sinus tachycardia with minimal loss of sensitivity for VT.128 Sorin ICDs classify

V.C.7 VT 3 DAYS POSTDISCHARGE ECG

T

T

T 100

T 100

T 100

T 100

T 100

T 100

T 100

T 100

T

438

434

441

438

438

445

445

445

441

441

445

441

445

R

R

R

R

R

R

R

R

R

R

R

R

R

R

R

X

Sinus rhythm T 100

438

434

R

R

S

S

100

R

691

691

R

R

T

100

T

438

T

100

T

441

100

100

T

430

T

100

T

95

RV

100

T

0

X T

100

X T

X T

0 0 0 VT: Predischarge EPS

10

379

379

383

R

R

R

0

11

Figure 3-61  Failure to detect ventricular tachycardia (VT) because of inappropriate classification of VT as supraventricular tachycardia (SVT) by morphology algorithm (St. Jude MD). Upper panel, Programmer strip from symptomatic tachycardia classified as SVT 3 days after implantation. Electrocardiogram (ECG), event markers, and right ventricular (RV) true bipolar EGM are displayed. Morphology match is 100% on most beats. The 12-lead ECG showed a left bundle branch block–type pattern, a broad R wave in V1 (distinctly different from conducted sinus QRS complexes), and atrioventricular (AV) dissociation. Lower panel, Event markers and RV EGM during tachycardia (left), sinus rhythm after manually delivered antitachycardia pacing (center), and induced VT at predischarge electrophysiologic study (EPS) (right). EGM morphology during spontaneous VT and sinus rhythm are similar and distinct from induced VT at predischarge EPS. True bipolar EGMs fail to distinguish VT from SVT in 5% to 10% of VTs.

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SECTION 1  Basic Principles of Device Therapy

nonconducted, it is considered ventricular in origin. Individual examples are shown in Figures 3-63 to 3-66. As in the electrophysiology laboratory, pacing methods may also be used to discriminate 1 : 1 tachycardias (see Active Discrimination).

300 VF

AF/VF

Ventricular rate (bpm)

250 (A-rate, V-rate)

(A=V) ST/VT/VF

200 VT 150

VF Interval (V>A)

100

AT/VT

VT Interval

(A>V) Sinus

50

AF/VT

AT

AF

Operation for Atrial Rate Greater Than Ventricular Rate The building blocks used by each manufacturer for distinguishing rapidly conducted AF and atrial flutter from VT during atrial arrhythmias are summarized in Table 3-3. Although various combinations of these building blocks successfully discriminate VT from SVT in VT zones, most VT during AF is sufficiently rapid to be detected in the VF zone,129 where some discriminators lose specificity or may not be applied at all. For example, R-R regularity cannot be applied in the VF zone because polymorphic VT has irregular R-R intervals, and undersensing of VF exaggerates the irregularity of measured R-R intervals. AV dissociation occurs uniformly during rapidly conducted AF,68 and morphology templates acquired during sinus rhythm often misclassify aberrantly conducted beats. Individual examples are shown in Figures 3-67 to 3-69. Specific Algorithms

0 0

100

200

300

Atrial rate (bpm) Figure 3-62  Dual-chamber “rate plane” highlights power of atrial versus ventricular rate. Dual-chamber rhythm classification can be visualized as a graph that plots atrial rate (A-rate) on the abscissa and ventricular rate (V-rate) on the ordinate. All points above the horizontal line representing the ventricular tachycardia (VT) intervals will be detected as VT or ventricular fibrillation (VF) on the basis of ventricular rate alone. Points that are both above this line and above and to the left of the line of identity are VT, and no additional discriminators need to be applied in this region, provided that atrial sensing is reliable. These discriminators can be restricted to rhythms with 1 : 1 atrioventricular (AV) relationship on the line of identity and those in which the atrial rate exceeds the ventricular rate in the region below and to the right of the line of identity. AF, Atrial fibrillation; AT, atrial tachycardia; ST, sinus tachycardia. (Modified from Morris M, Marcovecchio A, KenKnight B, et al: Retrospective evaluation of detection enhancements in a dualchamber implantable cardioverter defibrillator: implications for ICD programming [abstract]. Pacing Clin Electrophysiol 22:849, 1999.)

the 1 : 1 tachycardias based on “chamber of acceleration”: the first accelerated cycle is classified as “supraventricular” if two ventricular events are classified as “conducted,” if the R-R interval is greater than 75% of the preceding P-P interval. If the two ventricular events defining the first accelerated interval are ‘ ‘conducted,’ ’ the origin of the acceleration is declared “atrial.” Conversely, if the first accelerated beat is

TABLE

3-2 

Figures 3-70 to 3-74 show block diagrams of the principal dualchamber detection algorithms in clinical use today. Legends identify unique features of each algorithm. Single-Chamber vs. Dual-Chamber Discriminators Nominal programming of dual-chamber algorithms is safe.130,131 Dualchamber stored EGMs provide higher diagnostic accuracy for troubleshooting than single-chamber stored EGMs. However, dual-chamber discriminators cannot be implemented without the complications inherent in atrial leads. Also, dual-chamber ICDs introduce unique risks for underdetection of VT caused by cross-chamber ventricular blanking after atrial pacing (see Intradevice Interactions). In addition, with early dual-chamber algorithms, optimal values of programmable parameters were not known; initial approaches to the problem of atrial blanking versus FFRW oversensing had limited success; and atrial sensing problems and specific design flaws degraded performance. Not surprisingly, clinical studies of early dual-chamber algorithms reported no benefit over single-chamber algorithms.67,68,132,133 More recent, randomized prospective studies demonstrate moderate superiority in SVT-VT discrimination for dual-chamber over single-chamber algorithms.134,135 However, no agreement exists as to when the incremental implant complexity, price, risk of atrial lead complications, and reduced longevity of a dual-chamber ICD are justified for SVT-VT discrimination alone. Generally, dual-chamber ICDs should be considered in patients who are likely to have rapidly conducted SVT, those in whom monomorphic VT and sinus tachycardia rates are likely to overlap, and those who will benefit from additional diagnostics for atrial arrhythmias. Text continued on page 101

Discrimination of Tachycardias with Atrial Rate Equal to Ventricular Rate

Building Blocks Single chamber R-R stability P-P stability Sudden onset VEGM morphology Dual Chamber A rate vs. V rate P-R patterns AV association Chamber of acceleration

GDT Rhythm ID

Medtronic PR Logic

X

X [X] {X}

St. Jude Rate Branch

Sorin Parad+

Biotronik SMART

X

X

(X) X (X) [X]

X X

X X X X

X X X

X

GDT, Boston Scientific; VEGM, ventricular electrogram; A, atrial; V, ventricular; AV, atrioventricular. X, Algorithm uses this building block; [X], new PR Logic ST rule (Entrust) uses sudden R-R and P-R onsets; (X), “implicit” use of these building blocks via pattern analysis; {X}, Protecta ICDs (investigational) integrate Wavelet VEGM morphology into dual-chamber interval analysis.



3  Sensing and Detection

97

Date Time Type 17 - MAR - 2003 12:18 Spontaneous tial Detection Parameters 20 VF: 00 VT: SVT Inhibit = On, SRD 3:00 m:s 50 VT-1: SVT Inhibit = On Nonsutained Rhythm Average V Rate

SVT 158 bpm

End of Episode

25 cm/s

RA RV Tip–RV Coil

Shock AS ––

VS ––

AS 503

VS 543

VS 430

AS 508 VS 510

AS 415

AS 348 VS 440

VS 420

AS 375 VT-1 380

AS 363

AS 320

VT-1 365

(AS) 350

(AS) 378

VT-1 VS-Hy 335 405

(AS) 375

AS 398

AS 355

AS 338

(AS) 355 (AS) 318

VT-1 VT-1 VT-1 353 VT-1 365 VT-1 385 358 370

VT-1 383 VT-1 328 Epsd

Figure 3-63  Appropriate rejection of supraventricular tachycardia (SVT) with 1 : 1 atrioventricular (AV) conduction by AV relationship and morphology algorithm. Right atrial (RA), right ventricular (RV) rate-sensing, and Shock EGMs are shown in order with dual-chamber event markers. SVT begins with gradual warm-up, accelerating from a cycle length of approximately 540 msec to 380 msec in 3 seconds. The Boston Scientific Rhythm ID algorithm classifies morphology as SVT based on 1 : 1 AV association combined with constant shock morphology and constant timing relationship between peaks of two ventricular EGMs. The label ATR at bottom of event markers indicates that the rhythm is classified as SVT. Upper panel shows episode summary classifying rhythm as SVT.

TABLE

3-3 

Discrimination of Tachycardias with Atrial Rate Greater than Ventricular Rate

Building Blocks Single Chamber R-R stability P-P stability VEGM morphology Dual Chamber A rate vs. V rate P-R patterns AV association

GDT Rhythm ID

Medtronic PR Logic

St. Jude Rate Branch

Sorin Parad+

Biotronik SMART

X

X X {X}

X

X

X X

X X X

X

X X

X

X

X X

X

A, Atrial; AV, atrioventricular. GDT, Boston Scientific; X, Algorithm uses this building block; {X}, Protecta ICDs (investigational) integrate Wavelet VEGM morphology into dual-chamber interval analysis; V, ventricular; VEGM, ventricular electrogram.

98

SECTION 1  Basic Principles of Device Therapy

SINUS TACHYCARDIA

VT WITH 1:1 RETROGRADE CONDUCTION

P R

P R A Programmable 1:1 VT-ST boundary (nominally 50% R-R interval)

N Programmable 1:1 VT-ST boundary (nominally 50% R-R interval) Junctional Retrograde Antegrade

A Sinus tachycardia

VT with 1:1 retrograde conduction

1 1 1 1 1 1 1 1 1 1 3 2 2 3 2 2 3 3 3 3 3 3 3 3 7 6 6 7 7 7 7 7 7 7 5 2 9 8 1 8 8 3 1 1 0 0 0 0 0 A 0 A 0 A 0 A0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 S S S S S S S S S S S S S S S S S S S S S S S S S

P-R (ms) Marker events R-R (ms)

V V V V V V V V V V V T T T T T T T T T T T T T T T T S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 3 S3 S3 S 3 S 3 S 3 S 3 S 3 S 4 S4 S 3 S 3 S 3 S3 S 3 S 3 D 9 9 9 9 9 9 7 8 5 7 8 6 6 6 6 6 4 3 9 9 6 9 6 6 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

300 P-R (ms) 200 100 500 R-R (ms) 400 300

B

1:1 A:V conduction

P-R expected range

Sudden P:R change

R-R expected range VT/VF therapy zone

Gradual R:R change

VT DETECTED

Figure 3-64  A, Discrimination of 1 : 1 tachycardias by P-R pattern using the original sinus tachycardia criterion in Medtronic PR Logic (GEM III, Marquis, Maximo, InSync Marquis, InSync Maximo) ICDs. PR Logic uses patterns of A-V, V-A, V-V, and A-A intervals from consecutive ventricular events to form couple codes describing supraventricular tachycardias (SVTs). These couple codes are based on the number of atrial (A) events within the ventricular (V) interval and their relative timing. Discrimination of sinus tachycardia (ST) from ventricular tachycardia (VT) with 1 : 1 retrograde conduction is critically dependent on the programmable 1 : 1 VT-ST boundary, which is defined nominally as 50% of the current R-R interval (with optional values of 35%, 66%, 75%, and 85%). P-R intervals less than the defined percentage of the current R-R interval and greater than 70 msec are considered antegrade (left panel), and P-R intervals equal to or greater than that percentage of the R-R interval and also greater than 40 msec are considered retrograde (right panel). Rhythms in the detection zone with 1 : 1 pattern and antegrade P-R intervals are classified as ST, and therapies are withheld. Rhythms with 1 : 1 pattern and retrograde P-R intervals are classified as VT. B, New adaptive ST rule in PR Logic (Medtronic Entrust DR ICD) no longer uses 1 : 1 VT-ST boundary to discriminate ST from VT with 1 : 1 retrograde conduction. Rather, it uses a combination of pattern, sudden R-R onset, and sudden P-R onset. Operation of the new adaptive ST criterion is illustrated by this example of a spontaneous episode of ST that converted into VT with 1 : 1 retrograde conduction. During the ST, the R-R and P-R intervals occurred within their expected ranges. After initiation of VT, the R-R and P-R intervals occurred outside their expected ranges. Evidence of ST was lost by the third beat of VT. The sudden change in R-R intervals was small (460 msec), so the R-R intervals during the VT occurred within twice the R-R interval expected range, and adaptation of the RR interval expected range continued. Eventually, the R-R interval expected range adapts to accept the R-R intervals of the VT. Conversely, the P-R intervals occurred outside of twice the P-R expected range, and adaptation was inhibited. VT is appropriately detected after 16 consecutive R-R intervals in the VT detection zone despite gradual R-R onset of a 1 : 1 rhythm, because the P-R intervals had sudden onset and were no longer within the expected P-R interval range. VF, Ventricular fibrillation. (From Stadler RW, Gunderson BD, Gillberg JM: An adaptive interval-based algorithm for withholding ICD therapy during sinus tachycardia. Pacing Clin Electrophysiol 26:1189-1201, 2003.)



3  Sensing and Detection

99

AEGM

VEGM

P-R Intervals A S

V

R-R Intervals

1 5 A0 S

1 5 A0 S V S

7 7 0

1 9 A 0 R V S

4 0 0

V S

3 5 0

1 6 A 0 R T S

3 3 0

1 9 T 0 S T F

3 6 0

1 8 A 0 R T S

3 6 0

1 6 A0 R T S

3 4 0

1 5 T0 S T S

3 2 0

1 6 T 0 S T S

3 4 0

1 6 T0 S T S

3 4 0

1 7 T0 S T S

3 5 0

1 6 T 0 S T S

3 4 0

1 6 T 0 S T S

3 4 0

T S

Interval (ms)

Detection Burst

1 2 T0 S

1 2 T0 S

T 3 F 0 0

3 0 0

1 1 T0 S

T T F 3 F 0 0

1 6 T 0 S

3 6 0

1 1 T0 S T S

4 T0 S

T T 2 F 2 P 9 6 0 0 FVT

Term.

1500 1200 900 600 400 200

ATP

212

210

28

26

24

22 0 2 Time (sec)

4

6

8

10

12

Figure 3-65  Appropriate detection of ventricular tachycardia (VT) with 1 : 1 ventricular-atrial (VA) conduction by abrupt change in P-R pattern and ventricular rate. Upper panel, Dual-chamber stored EGMs and dual-chamber EGM markers. Note that upper numerical values indicate P-R interval, not P-P interval. Lower panel, Interval plot. VT starts in the ventricle with a premature ventricular complex, followed by abrupt change in ventricular rate, ventricular EGM morphology, and the PR-RR relationship (Medtronic PR Logic). Fast VT (FVT) detection at right of EGM is followed by burst antitachycardia pacing (VT Rx 1 Burst), designated by ATP on interval plot. This results in abrupt termination of VT. Note that older versions of this algorithm, which discriminated VT from SVT based only on the PR-RP percentage, may have classified this long-RP tachycardia incorrectly as SVT. AEGM, Atrial electrogram; TF, interval in FVT zone; TS, interval in VT zone; VEGM, ventricular (true bipolar) electrogram; VS, ventricular sensed event.

Figure 3-66  Classification of 1 : 1 tachycardias by chamber of origin. The Sorin Parad algorithm classifies 1 : 1 tachycardias by chamber of onset. Stored ventricular EGM is shown with dual-chamber event markers (top, atrial; bottom, ventricular). Event log and Event summary are shown above each stored EGM. Upper panel, Supraventricular tachycardia (SVT) is diagnosed by atrial onset. Lower panel, Ventricular tachycardia (VT) is diagnosed by ventricular onset.

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SECTION 1  Basic Principles of Device Therapy

Figure 3-67  Ventricular tachycardia (VT) during rapidly conducted atrial flutter discriminated by morphology of ventricular EGM. VT occurs during atrial flutter with 2 : 1 atrioventricular (AV) conduction. Time line marks indicate that the ventricular rate had been in the VT zone for 24 seconds at the beginning of the panel. VT therapy is withheld because of both the 2 : 1 AV relationship and the morphology match of ventricular EGMs to baseline sinus-rhythm EGMs (not shown). Numbers below event markers indicate 98% to 100% morphology match in atrial flutter, compared with 40% to 47% match in VT; “ (A rate + 10 bpm)

ACTIVE DISCRIMINATION

Yes

VT

No VTC rhythm No correlated? Yes SVT

A rate >200 bpm and No V rate unstable (>20 ms)

VT

Yes SVT

Figure 3-70  Boston Scientific Rhythm ID algorithm. The central features of this algorithm are comparison of atrial (A) and ventricular (V) rates (first step) and analysis of ventricular EGM morphology (Vector Timing and Correlation, or VTC). If the V rate exceeds the A rate by at least 10 bpm, the rhythm is classified as ventricular tachycardia (VT). If at least 3 of the last 10 beats are classified as supraventricular by morphology analysis, the rhythm is classified as supraventricular tachycardia (SVT). If morphology analysis does not classify the rhythm as SVT, the A rate and the regularity of the V rate are evaluated. The rhythm is classified as SVT if the A rate exceeds 200 bpm and the ventricular rhythm is irregular (measured ventricular interval stability >20 msec). Otherwise, it is classified as a VT.

Active discrimination represents a paradigm shift in the design of detection algorithms, from “diagnose before intervening” to “treat first; analyze only those tachycardias that persist after treatment.” Although active discrimination presents the risk of proarrhythmia (Fig. 3-75), it can be valuable in discriminating tachycardias with 1 : 1 AV association (Figs. 3-76 and 3-77). One such algorithm was designed and implemented by Biotronik (and incorporated into the SMART-II algorithm) but is not commercialized in Biotronik ICDs.136 Feasibility investigations recently demonstrated a new algorithm using simultaneous atrial and ventricular ATP either to terminate or to discriminate 1 : 1 tachycardias. If the tachycardia persists after the simultaneous AV ATP, the discrimination algorithm considers the rhythm ventricular in origin, if the first sensed event after pacing is on the ventricular channel, and supraventricular in origin otherwise. In 62 ambulatory dual-chamber ICD patients, the algorithm terminated or correctly classified 1379 of 1381 SVT sequences (specificity 99.9%) and 23 of 26 VTs (sensitivity 88.5%).115 FEATURES TO OVERRIDE DISCRIMINATORS Programmable duration-based “safety net” features deliver therapy if an arrhythmia satisfies the ventricular rate criterion for a sufficiently long duration even if discriminators indicate SVT. The premise is that VT will continue to satisfy the rate criterion for the programmed duration, whereas the ventricular rate during transient sinus tachycardia or AF will decrease below the VT rate boundary before the programmed duration is exceeded. The limitation is delivery of inappropriate

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SECTION 1  Basic Principles of Device Therapy

A-V RATE BRANCH Median atrial rate/ median ventricular rate

V A). If V < A, the algorithm applies morphology discrimination (and/or both interval stability and N:1 AV association). If V = A, it applies morphology discrimination (and/or sudden onset). All rhythms in the V > A rate branch are treated as ventricular tachycardia (VT). ST, Sinus tachycardia; SVT, supraventricular tachycardia; VF, ventricular fibrillation.

BIOTRONIK SMART

V rate > A rate

V rate = A rate

V rate < A rate

V unstable

V stable

N:1 multiplicity

A unstable

No N:1 multiplicity

V unstable

V stable

A stable

AV trend

VT

AFlut

VT

AFib

VT

VT

AV irregular

AV regular

No AV trend

Sudden onset

No sudden onset

VT

Sinus T

VT

1:1 SVT

Figure 3-72  Biotronik SMART algorithm. The high-level structure of this algorithm is similar to that of the St. Jude ICD. SMART first compares atrial (A) and ventricular (V) rates. If the V rate is faster, ventricular tachycardia (VT) is diagnosed. If the V rate is slower, ventricular interval stability and A : V ratio analysis results in discrimination of atrial fibrillation (AFib; unstable ventricular rhythm), atrial flutter (AFlut; stable rhythm, N:1 association), and VT (stable rhythm, AV dissociated). If the A rate and V rate are equal, SMART analyzes the interval stability. If the R-R interval is stable and the P-P interval is unstable, VT is diagnosed. If the PP interval is stable, the algorithm sequentially analyzes AV association (“AV Trend”) and sudden onset as discriminators. Sinus T, Sinus tachycardia; SVT, supraventricular tachycardia.



3  Sensing and Detection

A rate < V rate (Many RRs don’t have Ps) A R

Building blocks

Possible classification

T S

T S

A rate = V rate (Most RRs have only 1 P)

A R T S

T S

VT/VF (not SVT)

A R T S

A R T S

A R T S

A R T S

T S

A R T S

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A R

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VT/VF + SVT

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Atrial fib/flutter

VT/VF (not SVT)

ST/AT (w/FFRW OS) VT/VF

• R-R intervals • PR patterns

• RR intervals • PR patterns

Get more data

A rate > V rate (Most RRs have more than 1 P)

A R

103

Process PR logic building blocks (up to 24 R-R intervals and P:R patterns)

A R T S

VT/FVT/VF detection by RR intervals? Yes

No

Yes Median RR < SVTLimit? No

Yes

Double tachycardia identified? No

• RR intervals • PP intervals • PR patterns • RR regularity • PR dissociation • PP regularity

AFib/AFlutter?

Yes

No Sinus tach?

Yes

No Other 1:1 SVT?

Yes

No VT/FVT/VF DETECTION

A

B

Figure 3-73  Medtronic PR Logic algorithm. A, Clinical decision process. The rhythm types are represented using P-R marker diagram examples (top), from least complex (left) to most complex (right). A list of possible PR Logic decisions and the building blocks used are also shown for each of the rhythm types. Note that PR Logic implicitly employs a ventricular (V) rate > atrial (A) rate override (first column), because all rhythms with A rate < V rate and V rate in one of the detection zones are classified as ventricular tachycardia/fibrillation (VT/VF). For tachycardias with A rate = V rate (i.e., 1 : 1 tachycardias, center column), the original PR Logic uses P-R patterns and discriminates 1 : 1 rhythms with critical P-R interval timing zones (see Fig. 3-64, A). The new sinus tachycardia (ST) criterion in PR Logic (Entrust and later) uses the P-R pattern along with P-R and R-R suddenonset criteria (see Fig. 3-64, B). For rhythms with A rate > V rate, PR Logic uses P-R patterns along with R-R regularity, P-R dissociation, and P-P regularity to ensure detection of double tachycardia (VT or VF during atrial fibrillation [AFib]) and to withhold therapy for 2 : 1 atrial flutter, rapid AFib, and ST with far-field R-wave oversensing (FFRW OS). In the newest Medtronic ICDs (Protecta, currently investigational), EGM morphology analysis (Wavelet) is applied for rhythms with A rate ≥ V rate that are identified by SVT by PR Logic pattern analysis alone. In addition, detection of double tachycardia in the Protecta devices requires that abnormal EGM morphology be present. Integration of Wavelet EGM morphology with PR Logic is designed to improve detection specificity compared to PR Logic interval analysis alone. B, PR Logic computational flow diagram. On each ventricular event, PR Logic processes the new P-R, R-P, P-P, and R-R patterns and timing information for the building blocks. If VT/fast VT (FVT) or VF rate detection criteria are satisfied, the ventricular rate override criterion is checked first. If the median R-R interval is less than the supraventricular tachycardia (SVT) limit, detection occurs through the single-chamber detection criteria without considering the PR Logic discrimination algorithm. If the median R-R interval is greater than the SVT limit, and if double tachycardia (VT/FVT/VF + SVT) is not detected, the three PR Logic criteria for identifying SVTs are tested in the order shown. If any one of the PR Logic SVT criteria is satisfied, inappropriate detection is avoided. If an SVT is not positively identified by PR Logic pattern analysis and the A rate ≥ V rate, EGM morphology analysis (Wavelet) is applied and classify the rhythm as SVT if the EGM morphology during tachycardia matches the template. If none of the SVT discrimination criteria is satisfied, VT/FVT/VF is detected when the R-R interval–based criterion is satisfied. If SVT is identified, the entire process repeats itself on each ventricular event until VT/FVT or VF is detected or the rhythm slows out of the ventricular rate detection zones.

therapy when SVT exceeds the programmed duration, which occurs frequently for durations of 1 minute or less and in up to 10% of SVTs at 3 minutes, depending on the VT detection interval and AV conduction.116 Because SVTs are much more common than VTs, programming of discriminator override duration to 3 minutes results primarily in inappropriate therapy of SVT. Programmed durations of 5 to 10 minutes are required to minimize such inappropriate therapy.137 The decision to use a discriminator override should be based on clinical factors, including the probability that discriminators will prevent detection of VT, the likely consequences of failure to detect VT, and the likelihood that SVT in the VT rate zone will persist long enough to trigger inappropriate therapy because of the override. For example, override features may be considered whenever a morphology algorithm is programmed without inducing VT at electrophysiologic study. The Medtronic Protecta ICDs incorporate an additional, separately programmable “VF Zone High Rate Time Out.” It applies only to rhythms that are consistently in the VF rate detection zone. This new algorithm allows SVT discriminators to be applied with

longer-duration (or no) time-out for slower rhythms, with a separate override duration for rhythms with rates in the VF zone. SVT-VT DISCRIMINATORS IN REDETECTION The SVT-VT discrimination during redetection serves two purposes: (1) to prevent inappropriate therapy for SVT after appropriate therapy for VT (Fig. 3-78) and (2) to provide a second chance for the algorithm to classify SVT correctly after inappropriate therapy. Biotronik ICDs (Fig. 3-79) and sorin-ELA ICDs provide essentially equivalent SVT-VT discrimination in initial detection and redetection, except that algorithm building blocks related to tachycardia onset are disabled. Boston Scientific algorithms permit programming discriminators after shocks, but not after ATP, when it is more useful and reliable. In Medtronic ICDs, the single-chamber stability discriminator applies to redetection only if it is “on” for initial detection. The user interface does not indicate that it applies in redetection, and it is rarely programmed for this purpose. St. Jude ICDs do not apply discriminators to redetection.

104

SECTION 1  Basic Principles of Device Therapy

Tachyarrhythmia detected

Unstable

RR Stability

Diagnosis AF No VTLC No Diagnosis VT

Inappropriate Detection, Inappropriate Therapy, and Inappropriate Shocks All failures of SVT-VT discrimination algorithms do not have equivalent clinical outcomes. ATP is delivered immediately after detection so the numbers of detections and therapies are equivalent. In contrast, shock delivery requires capacitor charging, during which therapy may be aborted. However, inappropriate ATP is often unnoticed. It terminates about 40% of SVTs and reduces the ventricular rate below the VT detection interval in another 20%.139 In contrast, inappropriate shocks adversely affect quality of life.140 Active discrimination blurs the distinction between detection and therapy because only tachycardias that persist immediately after diagnostic pacing are classified.

Stable

Associated PR Yes Yes

Diagnosis No AF Diagnosis AFlutter

PR Association 1:1 Gradual

Diagnosis ST

IS VENTRICULAR THERAPY FOR SVT ALWAYS INAPPROPRIATE?

Acceleration Sudden Origin of acceleration Atrial

Diagnosis AT

Ventricular Diagnosis VT

Figure 3-74  Sorin Parad+ algorithm. If most of the detected R-R intervals are in the ventricular tachycardia (VT) zone, ventricular interval stability is analyzed in a first step, using a histogram of R-R intervals. If the rhythm is irregular, atrial fibrillation (AF) is diagnosed and therapy is withheld. If the rhythm is regular, the atrioventricular (AV) association is assessed by comparing peak amplitudes of R-R and P-R interval histograms. If the rhythm is AV dissociated, VT is diagnosed, unless the Long Cycle Search is activated, which inhibits therapy if a long ventricular cycle (VTLC, characteristic of AF) is identified. If N:1 P-R association is identified, the rhythm is classified as supraventricular tachycardia (SVT). In the presence of 1 : 1 P-R association, the Parad+ evaluates the rate of acceleration of the ventricular rate. If acceleration is gradual, sinus tachycardia (ST) is diagnosed. If acceleration is sudden, Parad+ identifies the chamber of origin and withholds therapy if it is the atrium. AFlutter, Atrial flutter; AT, atrial tachycardia.

Neither Medtronic nor St. Jude ICDs provide any discriminators to reject sinus tachycardia in redetection. MEASURING PERFORMANCE OF SVT-VT DISCRIMINATION ALGORITHMS Valid assessments and comparisons of algorithm performance require consideration of multiple ICD-related and clinical factors. A comprehensive assessment requires analysis of all tachycardia episodes, including those not stored in ICD memory and those in the VF zone to which discriminators may not apply.68,69,130 Programmed detection parameters may influence reported algorithm performance.69 In most studies, a few patients contribute a large number of SVT or VT episodes. Therefore, statistical methods such as the generalized estimating equation (GEE)138 should control for such clustered, nonindependent data. Quantitative Considerations Detection algorithms must maintain almost 100% sensitivity for detection of VT; but detection of hemodynamically-stable asymptomatic VT is not necessarily synonymous with therapy. If patient populations and programmed detection boundaries are equivalent, positive predictive accuracy may be the most useful statistical measure of algorithm performance.68 However, it is highly dependent on the ratio of SVT to VT episodes and therefore on the programmed detection rate and patient population (prevalence of SVT and VT). However, it is almost impossible to obtain a clinically meaningful comparison of different detection algorithms based only on their performance on different sets of data.

Persistent, rapidly conducted atrial arrhythmias can cause hemodynamic compromise in patients with LV dysfunction or ischemia in patients with severe coronary artery disease. Thus, algorithmically inappropriate ventricular therapy may fortuitously terminate clinically significant SVT, although inappropriate ventricular therapy for SVT may also be proarrhythmic.141 Further, in patients with ICDs, rapid conduction in AF is often transient, and symptoms are often mild, but ventricular shocks delivered shortly after detection do not permit spontaneous termination of AF or slowing of the ventricular rate. Therefore, shocks will be delivered for AF that may have spontaneously terminated or slowed. Inappropriate shocks for AF may place patients at risk for thromboembolism if they are not anticoagulated. Also, early recurrence is common after transvenous cardioversion of AF.142 Experts differ about whether algorithmically inappropriate ventricular therapy of SVT may be clinically appropriate in specific clinical situations. ICDs designed to deliver both atrial and ventricular therapies may be implanted in patients who are likely to benefit from ICD-based therapy of SVT.

Detection: Programming and Troubleshooting The multiple programmable parameters that affect detection directly or indirectly provide opportunities both for customizing detection and for operator error. A prospective study reported that empirical programming of dual-chamber ICDs provided comparable performance to individualized programming.131 Nevertheless, it is important to understand the many trade-offs and compromises inherent in ICD detection strategies. DETECTION ZONES AND DURATION Zones and Zone Boundaries In patients receiving secondary prevention therapy, typical values for rate zone boundaries are 400 to 360 msec for the sinus-VT boundary, 330 to 240 msec for VT–fast VT boundary, and 300 to 240 msec for the upper limit of the VF zone boundary, with longer cycle lengths for the last boundary usually found in two-zone programming. In primary prevention patients and those whose only arrhythmia is VF, typically one or two zones are programmed, with the sinus boundary set at 330 to 300 msec.143,144 This approach lowers the risk of inappropriate therapy but increases the risk of not treating VT. Programming that permits delivery of ATP is desirable for most patients, even those undergoing implantation for primary prevention and those whose only clinical arrhythmia is VF, because most spontaneous VF begins with rapid VT, and most rapid VT can be terminated by ATP.145-147 Three zones permit different ATP therapies for two distinct rates of VT, as well as ATP for monomorphic VT that overlaps in rate with polymorphic VT. In the largest primary prevention trial,144 ICDs were programmed to a single detection zone at a cycle length of 320 msec, without SVT-VT discriminators, but approximately one



105

3  Sensing and Detection

RA ATP

ATP ATP

413

373

S

S

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ATP ATP

T

T

T

T

T

422 422 422 422 422 422 418 434 422 418 426 422 422 410

493 P

ATP

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ATP ATP ATP ATP ATP ATP ATP ATP D 423 423 413 431 399 443 423

R

ATP ATP ATP ATP ATP ATP ATP ATP

RV 32

33

34

35

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40

DDI

Proarrhythmia ATP in 1:1 SVT (rapidly conducted AF)

T

F

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40 DDI

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F

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42

F

F 8V

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328 293 301 289 305 371 426 344 430 414 397 P P P R R R R R R

48

49

* R

* R

* R

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F

F

F

F

* R

* R

* R

* R

* R

* R

* R

H V

* R

R R D 309 301 281 285 324 465 309 297 461 473 309 309 320 297 305 324 316 355 262 289 301 270 426 277 242 246 242 254 316 383 281 281 301 270 281 293 387 309 P R R R R R R R R R R R R R R R R R R R R R R

320 332 293 348 305 441 R

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* R

50

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* R

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51

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R

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44

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* R

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45

* R

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* R

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47

* R

* R

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48

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D 26 293 289 309 305 230 297 320 277 293 273 277 285 273 293 258 324 336 418 328 293 297 273 258 309 305 324 277 313 35 P P R R R R R R R R R R R R R R R R

52

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H V 830V

6 262 445 281 648 309 289 2 324 285 254 285 285 266 297 313 273 R

48

R

R

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49

R

R

R

50

R

R

51

Figure 3-75  Atrial proarrhythmia caused by ventricular antitachycardia pacing in 1 : 1 supraventricular tachycardia (SVT). Continuous stored EGM shows right atrial (RA) EGM, event markers, and true bipolar right ventricular (RV) EGM. In the top panel, antitachycardia pacing (ATP) is delivered after rate-only, inappropriate detection of sinus tachycardia as ventricular tachycardia. Ventricular-atrial conduction occurs, initiating atrial fibrillation (AF), which is detected as ventricular fibrillation because redetection does not utilize discriminators. AF requires two shocks (HV) before termination. The first shock is delivered at the end of the middle panel and the second in the middle of the lower panel. Recording is suspended for approximately 1 second after each shock.

106

SECTION 1  Basic Principles of Device Therapy

EGM1: Atip to Aring

EGM2: Can to HVB 3 1 0

A-A interval (ms) Marker annotation

T S

V-V interval (ms)

3 1 0

3 1 0

A A S S

A S

3 2 0

A S

T T T S S S 3 3 3 1 1 1 0 0 0

3 2 0

3 3 3 2 2 2 0 0 0 A A A A S S S S

6 4 0

A S

T T T T T T T S S D P P P P 3 3 3 2 2 2 2 1 2 2 7 7 7 7 0 0 0 0 0 0 0

3 2 0

A S

3 2 0

3 1 0 A A S S

2 7 0

T T T T P P P P 2 2 2 2 7 7 7 7 0 0 0 0

third of shocks were inappropriate, most often for rapidly conducted AF. The sinus-VT rate boundary should be slow enough to ensure detection of all hemodynamically compromising VTs. To prevent underdetection of irregular VT, the VT detection interval should be set with a safety margin at least 40 to 50 msec longer than the slowest predicted VT for consecutive-interval counting and 30 to 40 msec longer for “X out of Y” or “interval + interval-average” counting.134 This safety margin should be greater if rapidly conducted SVT is unlikely or SVT-VT discrimination is reliable at long cycle lengths (Sorin ICDs). The boundary between the two VT zones should be based on the cycle length at which different types or fewer trials of ATP are preferred. The VT-VF rate boundary is based on the cycle length below which ATP or ATP before charging should not be delivered. In Medtronic ICDs, which use consecutive-interval counting above the VF interval and “X out of Y” counting below it, this boundary should be set to prevent underdetection of irregular, polymorphic VT by consecutive-interval counting.

A S

3 6 0

7 1 0

A S

3 1 0

V S

3 1 0

A A S S

3 1 0

T T S F 3 2 6 7 0 0

Figure 3-76  Effect of ventricular antitachycardia pacing on supraventricular tachycardia (SVT) with 1 : 1 atrioventricular (AV) relationship. Atrial EGM (Atip to Aring), high-voltage ventricular EGM (Can to HVB), and dual-chamber event markers are shown. Burst ventricular antitachycardia pacing at cycle length 270 msec is applied to SVTs with cycle lengths of 310 to 320 msec. The atrial interval after the last paced beat is accelerated to the pacing rate, probably indicating entrainment of the atrium. The A-A-V response at termination of pacing is diagnostic of atrial tachycardia.

Duration for Detection of Ventricular Tachycardia Detection duration before ATP should rarely be decreased from nominal values, because therapy is immediate after detection, and undersensing of monomorphic VT is rare. It should be increased in patients who have long episodes of nonsustained VT. Substantial increases in duration for detection of VT probably are safe in St. Jude and Boston Scientific ICDs, which use counting methods that are insensitive to occasional long ventricular intervals or undersensing. In contrast, consecutive-interval counting used by Medtronic ICDs in the VT zone and the Sorin persistence counter (nominally set to 12 consecutive intervals for VT and 6 for VF) may underdetect VT if occasional, long ventricular intervals or undersensing occurs.119 Duration for Detection of Ventricular Fibrillation Duration for detection of VF generally should not be reduced from nominal to prevent inappropriate therapy or aborted shocks for nonsustained VT.146,148 A prospective study of primary prevention patients demonstrated that long-duration detection (30/40 intervals) did not

A-EGM

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A R T S

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3 3 3 4 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 8 8 9 2 1 1 1 1 2 2 3 2 2 2 2 7 6 6 4 6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 A A A A A A A A A A A A A A A A A A A A R R R R S S S S S S S S S S S S R R R R T S

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T T T T T T T T T T T P P P P P P P P P P P 4 3 3 3 3 3 3 3 3 3 3 9 2 2 2 2 2 2 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0

V S

3 9 0

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3 8 0

Figure 3-77  Atrial response to ventricular antitachycardia pacing during ventricular tachycardia (VT) with 1 : 1 ventricular-atrial (VA) conduction. Stored atrial (A) and ventricular (V) EGMs are shown with event markers. During antitachycardia pacing, atrial rate accelerates to ventricular rate. The V-A-V response at termination of pacing is characteristic of VT, although atrioventricular (AV) nodal and AV reciprocating tachycardias cannot be excluded.



3  Sensing and Detection

107

RV Tip-RV Ring

RV Coil-Can T F 3 2 0

3 1 0

T F 3 2 0

T F 3 2 0

T F 3 3 0

VT

T F 3 3 0

T F 3 3 0

T F 3 3 0

T F 3 4 0

T F 3 3 0

T F 3 5 0

T F 3 4 0

T F 3 3 0

T F 3 4 0

T F 3 3 0

T F 3 4 0

ATP

T F 3 6 0

T F 3 6 0

T P

T P

T P3 6 0

T P2 9 0

T T P2 P 2 9 9 0 0

T P2 9 0

T P2 9 0

Sinus Tachycardia T F2 9 0

T F 2 9 0

T P2 9 0

T P

T S

8 1 0

ATP T• F

4 3 0

T• F

T• F

4 3 0

4 4 0

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T• F

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4 5 0

T• F

T P

4 4 0

T P

3 3 6 6 0 0 FVT Rx 1/Sec 2

T P

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3 6 0

T P

3 6 0

T F

4 6 2

T F

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Sinus Tachycardia T P

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14.9 J

A V-V 1,800

VF = 300 ms Burst

V-V interval (ms)

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FVT = 360 ms 20.1 J

VT = 470 ms 35.1 J

34.8 J

14.9 J

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1,200 900 600 Sinus Tach 400

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220

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0

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40

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*

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Time (sec) [0 = detection]

Figure 3-78  Redetection. Inappropriate therapy of sinus tachycardia after appropriate therapy for ventricular tachycardia (VT) in a singlechamber ICD. Ventricular sensing and high-voltage leads are shown with event markers. A, Continuous stored EGM strips after detection of VT. The top strip shows successful antitachycardia pacing (ATP) of VT followed by sinus tachycardia in the Fast VT (FVT) zone (TF on event markers). The second strip shows the first inappropriate sequence of ATP. The third strip shows the first of five shocks delivered after ATP. B, Interval plot shows the entire episode. No U.S. ICD manufacturer provides for VT-supraventricular tachycardia (SVT) discrimination after ATP. RV, Right ventricular; VF, ventricular fibrillation. (From Swerdlow CD, Friedman PA: Advanced ICD troubleshooting. Part II. Pacing Clin Electrophysiol 29:70-96, 2006.)

108

AFlut 399

AFlut 398

AFlut 399

VT1 390

VT1 398

VT1 399

AS 719 Ars 195 AS 203 AS 196 Ars 195 AS 203 AS 195 Ars 196 AS 203 Ars 195 AS 196 AS 203 Ars 195 VS 1844

AS Ars 109 VT2 320

20 J 81Ohm

25 AS 985 VS 984

AS 984 VS 984

VS 985

AS 985

AS 975

AS 985 VS 977

AS 984

Shock

VS 984

VS 984

AS 984

AS 985 VS 985

AS 726 VS 992

AFlut 391

AFlut 390

AFlut 391

AFlut 391

AFlut 398

AFlut 398

AS 195 AS 204 Ars 195 AS 195 AS 203 Ars 196 AS 203 Ars 195 AS 195 AS 203 Ars AS 125

25 mm/s

VS 984

Charge

VT2 328

VT2 321

VT2 328

VT2 351

AS 351

AS 352

VT2 352

AS 351

VT1 351

VT2 352

VT2 352

AS 704

AS 1617 VT2 320

VT2 328

VT2 320

VT2 321

VT2 328

AS 586 VT2 351

VT2 320

VT1

VT2 320

VT2 320

VT2 328

AS 750

AS 1617

SECTION 1  Basic Principles of Device Therapy

Figure 3-79  Supraventricular tachycardia/ventricular tachycardia (SVT-VT) discrimination in redetection. Dual-chamber EGM markers, atrial EGM, and true bipolar EGM are shown in this continuous strip from a Biotronik Lexos ICD, Model 347000. Rhythm at beginning of upper panel is VT with ventricular-atrial (VA) dissociation. Vertical dotted line indicates detection and start of capacitor charging (Charge). Black horizontal line indicates period of capacitor charging followed by successful shock. Postshock nonsustained atrial flutter begins toward right side of upper panel, continues into lower panel, and shows transient atrial flutter followed by conversion to sinus rhythm. Ventricular rhythm is classified by the lower row of markers as VT2 (faster VT zone) before shock, VT1 (slower VT zone) for the first four ventricular EGMs of atrial flutter, and conducted atrial flutter (Aflut) beginning at the fifth conducted ventricular EGM during atrial flutter (arrowhead). Without SVT-VT discrimination in redetection, VT would have been redetected after 10 intervals.

increase risk of syncope compared to historical controls.143 A significant reduction in heart failure hospitalization (as well as shocks) was reported in a controlled study of primary-prevention, nonischemic heart failure patients comparing detection duration of 12/16 with 30/40 intervals.149

redetection may prevent inappropriate redetection of delayed termination of VT (type II break) or postshock nonsustained VT. ICDs misclassify effective therapy as ineffective if VT/VF recurs before the ICD identifies episode termination and reclassifies the posttherapy rhythm as “sinus” (Fig. 3-80). Misclassification may also occur if SVT begins after successful VT therapy but before ICD-defined episode termination because of frequent premature beats or nonsustained tachycardia. Decreasing the duration for redetection of sinus rhythm (St. Jude) may correct this classification error.

Duration for Redetection Inappropriate therapy for nonsustained VT or SVT may be delivered after ATP or shocks (see Fig. 3-78). Increasing the duration for

5 3 0

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1600

A R V S

V S

5 7 0

2

5 5 0

A R

V 1 C S 9 E 0

4 2 0

V S

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C D 15.0

Figure 3-80  Failure to identify post-therapy sinus rhythm because of rapid reinitiation of ventricular tachycardia (VT) after successful therapy. Atrial EGM, ventricular true bipolar EGM, and EGM markers classify the rhythm as sinus (8 consecutive intervals). Therefore, VT is inappropriately redetected instead of being detected de novo for the second time. This results in delivery of the second programmed Fast VT (FVT) therapy, cardioversion, rather than repeat delivery of the previously successful antitachycardia pacing (ATP) stimulus, which is both painless and more energy efficient. Redetection marker (FV Rx 2 CV) indicates onset of capacitor charging for the second VT therapy. Shock is not shown. Large numbers below right side of upper panel and left side of lower panel show value of sinus rhythm counter, which increments for each interval in the sinus zone (VS) and is reset to zero by premature ventricular complexes (PVCs) with a coupling interval of less than the VT detection interval of 400 msec (TS). VS markers indicate unclassified ventricular intervals during capacitor charging. AS, Atrial sensed event; AR, atrial intervals in pacing refractory period.



3  Sensing and Detection

Recommended Programming of SVT-VT Discriminators in Dual-Chamber ICDs

RANGE OF CYCLE LENGTHS TO WHICH SVT-VT DISCRIMINATORS APPLY

TABLE

The SVT-VT discriminators apply in a range of cycle lengths bounded on the slower end by the VT detection interval and on the faster end by a minimum cycle length that varies among manufacturers (see Fig. 3-51). Usually, SVT-VT discriminators will not withhold inappropriate therapy for SVT if the majority of ventricular intervals (typically 70%80%) are shorter than the SVT limit. Therefore, rapidly conducted AF may be classified as VT even if the mean cycle length is 20 to 40 msec longer than the SVT limit. Programming a sufficiently short, minimum cycle length for SVT-VT discrimination is critical to reliable rejection of SVT. When discriminators are programmed, approximately 25% of inappropriate therapy is caused by SVT with ventricular cycle lengths shorter than that minimum cycle length.68,137,150 In some ICDs, the SVT discriminators can be programmed only in the VT detection zone if two-zone programming is used or in the slowest zone with three-zone programming. In currently approved Medtronic ICDs, the SVT limit is programmable independently, but the performance of SVT-VT discriminators is linked implicitly to the VT/VF zone boundary. AF is not rejected by RR regularity at cycle lengths shorter than the programmed VF detection interval; thus rapidly conducted AF cannot be distinguished from VF in dualchamber and cardiac resynchronization ICDs before the (now investigational) Protecta models. In nominal programming, the “VF Detection Interval” forms the boundary between the VT and Fast VT zones. Therefore, this degradation in discrimination of VT from rapidly conducted AF usually occurs between the VT and Fast VT zones. In these ICDs, conducted AF in the Fast VT zone may be discriminated by programming “Fast VT via VT” rather than the nominal “Fast VT via VF.” The risk is delay in detection of unusual, markedly irregular fast VT with occasional cycle lengths in the sinus zone.

Medtronic PR Logic AFib/AFlutter ON Sinus Tach ON*

Atrial View AFib Rate Threshold 200 bpm

Other 1 : 1 SVTs

Onset 9%

{Wavelet ON Match Threshold = 70%}, Protecta devices only (investigational)

Inhibit if unstable 10%

PROGRAMMING OF SVT-VT DISCRIMINATORS Single-Chamber Discriminators Technical details vary among manufacturers, as do corresponding recommended programmed values, which are summarized in Table 3-4. See earlier Ventricular EGM Morphology for SVT-VT Discrimination for programming and troubleshooting of morphology algorithms. Dual-Chamber Discriminators Dual-chamber algorithms should be programmed “on” in any patient with intact AV conduction and a functioning atrial lead. Specific considerations for each manufacturer are summarized in Table 3-5. In St. Jude ICDs, discriminators may be combined using either the “any” or “all” operators. Using “any,” the algorithm detects VT if any discriminator classifies the tachycardia as VT, resulting in higher sensitivity and lower specificity. Conversely, using “all,” the algorithm detects VT only if all discriminators classify the tachycardia as VT, resulting in lower sensitivity and higher specificity. The “all” operator corresponds to the addition of discriminators in other algorithms.

3-5 

109

Boston Scientific Rhythm ID ON

St. Jude Rate Branch Rate Branch ON A = V Branch: Morphology A > V Branch Morphology; may combine Stability† with “ANY” logic

V rate > A rate ON Sustained rate duration = 3 minutes *In older models before Entrust (Model D153DRG) (*1:1 VT-ST Boundary = 66%). †Stability at 80 msec with AV Association of 60 msec. A, Atrial; AFib, atrial fibrillation; Tach, tachycardia; V, ventricular.

St. Jude Rate Branch.  Morphology should be programmed in both the “V = A” and “V < A” rate branches. Recommended programming adds the stability discriminator in the V < A branch using the “any” operator. This results in a minor increase in sensitivity for detection of VT (98% to 99%) and a similarly minor decrease in specificity (82% to 79%). Addition of the stability discriminator using the “all” operator reduces inappropriate detection of aberrantly conducted AF, but may also reduce sensitivity for detection of VT.114 Boston-Scientific Rhythm ID.  This algorithm has no programmable features. Medtronic PR Logic.  At implantation, rejection rules should be programmed “on” for sinus tachycardia and atrial fibrillation/flutter. The 1 : 1 SVT rejection rule should not be programmed until the atrial lead is stable, because its dislodgement to the ventricle may result in misclassification of VT as a 1 : 1 SVT. This potential problem also applies to the St. Jude Rate Branch algorithm without additional discriminators.

Failure to Deliver Therapy: Undersensing and Underdetection Undersensing and underdetection may be caused by ICD system performance, programmed values (including human error), or a combination of the two. They result in failure to delivery therapy or delay in therapy. UNDERSENSING

TABLE

3-4 

Recommended Programming of SVT-VT Discriminators in Single-Chamber ICDs

Stability* Onset Morphology

Medtronic 40-50 msec, NID = 16 84%-88% 3 of 8 electrograms ≥70% match

Boston Scientific 24-40 msec, duration 2.5 sec 9% Not programmable†

St. Jude 80 msec 150 msec 5 of 8 electrograms ≥60% match

*Less strict values are required for patients taking type I or III antiarrhythmic drugs. †3 of 10 electrograms with Feature Correlation Coefficient greater than threshold. ICDs, Implantable cardioverter-defibrillators; NID, number of intervals to detect VT; SVT-VT, Supraventricular tachycardia–ventricular tachycardia.

Ventricular fibrillation may be undersensed because of combinations of programming (sensitivity, rate, or duration), low-amplitude EGMs, rapidly varying EGM amplitude, drug effects, and postshock tissue changes. At present, the most common causes of VF undersensing are drug or hyperkalemic effects that slow VF into the VT zone, ischemia, and rapidly varying EGM amplitude48,71 (Fig. 3-81). ICDs that adjust dynamic range based on the amplitude of the sensed R wave (Boston Scientific) may be the most vulnerable to rapidly varying EGM amplitude (Fig. 3-82). ICD features that reduce sensitivity to prevent T-wave oversensing may also result in undersensing of VF.60 Prolonged ischemia from sustained VT slower than the VT detection interval may cause deterioration of signal quality, resulting in undersensing of VF. Lead, connector, or generator problems may also manifest as undersensing.

110

SECTION 1  Basic Principles of Device Therapy

Near field V

VF 158

Pre-attempt EGM (10 sec max) Initial Detection VF Zone Pre-attempt AVS Rate 176 bpm

VF 248

Far field V

VF 253 Epsd Grad 1

VF 163

VF 265

VF 163

VF 263 VF 155

VF 280

VF 155

VF 270

VF 270 VF 168

VF 163

VF 265

VF 158

VF VF 283 270 VF VF 163 165

VF 278 VF 143

VF 303 VF 135

VF 305 VF 165

VF 280 VF 168

VF 278 VF 165

VF 290 VF 165

VF 278

VF 175

VF 278

VF 160

VF 300

VF 163

VF 298

VF 168

–– 533

VF 373 –– 98

VF 138 VS 465

VS 335 Dvrt

Chrg

A

End of Episode 00.25

Pre-attempt EGM (10 sec max) Initial Detection Pre-attempt AVS Rate 218 bpm

25 mm/s

VF –– 228 VF 165 230

VS 365

VS 478

VF 140

VS 345

VF 143

VS 345 VF 145

VS 353

VF 153

VS 353

VF 145

VT 310

VF 170

VS 355

VF 145

VS 368

VF 138

VT 315

VF 135 VS 425

VT 310

VF 173

VS 345

VF 145

VF 158 VS 355

VS 368

VS 543

VS 625

VS 578

VF 230

VF 228 Detct Chrg

VF 218

VF 190

VF 188

VF VF VF 135 223 225 VF VF VF VF 188 258 155 195

VS 383

VF 288

VF 243

VF 188

VF 178

VF 280

VF 218

VF 243

–– 170

Chrg

–– 223

VF 170

1

VF 260

VF 180

Shock

Attempt

VF 230

Attempt Type Elapsed Time Therapy Delivered

VF 208

14J Biphasic 00:01 VF Shock 1

Far field V

Pre-attempt EGM (10 sec max) Initial Detection Pre-attempt AVS Rate 60 bpm

Near field V

–– 1363

VS 1573

B Figure 3-81  Underdetection of ventricular fibrillation (VF) caused by hyperkalemia (potassium level, 6.7 mg/dL) in the setting of chronic amiodarone therapy. A, Near-field and far-field ventricular (V) EGM and event markers of a Boston Scientific Prizm VR ICD. The top panel shows a sine-wave ventricular tachycardia (VT) in the far-field channel, which is detected as VF because local EGMs on the near-field channel are doublecounted. At right of upper panel, four intervals greater than the programmed VF detection interval of 316 msec (190 bpm) result in an aborted shock. The lower panel shows persistence of VF after the shock is aborted. Too few intervals are sensed in the VF zone to permit detection of VF. The patient was resuscitated by external shock. B, ICD system testing after correction of hyperkalemia. Induced VF is sensed reliably and is terminated by an ICD shock. The near-field EGM is narrow, indicating that double EGMs present during the clinical arrhythmia were caused by functional conduction block. (Courtesy Dr. Felix Schnoell.)



3  Sensing and Detection

111

ECG

RA

RV (Tip-Coil)

(AS) 1343

PVC 303 VF 265

(AS) 1268

(AS) 1215 PVC 580

VS PVC 305 310

PVP

PVC 283

PVC 483

PVP

(AS) 1185

AS 1158

PVC VP-MT 320 VF 523 170 PVP

VP 555

PVC PVC 288 VF 330 273 PVP

VS 31

PVP

Figure 3-82  Undersensing of ventricular fibrillation (VF) despite normal R wave in sinus rhythm (18.5 mV). Programmer strip recorded at implantation testing of a Boston Scientific Prizm ICD shows electrocardiogram (ECG), right atrial (RA) EGM, and integrated bipolar right ventricular (RV) sensing EGM (Tip-Coil) during implantation testing. The VF EGMs have highly variable amplitudes, resulting in undersensing of low-amplitude EGMs immediately after high-amplitude ones (arrows). Intermittent ventricular pacing (VP) introduces postpacing blanking periods. Slow Automatic Gain Control may contribute to this type of undersensing. AS, atrial sensed event; PVC, premature ventricular complex; PVP→, extension of postventricular atrial refractory period (PVARP); VP, ventricular paced event. (Modified from Dekker LR, Schrama TA, Steinmetz FH, et al: Undersensing of VF in a patient with optimal R wave sensing during sinus rhythm. Pacing Clin Electrophysiol 27:833-834, 2004.)

ICD INACTIVATION If detection is programmed “off ” for surgery using electrocautery, reprogramming must be performed at the end of the procedure, a fact that is easily forgotten, especially with outpatient surgery. One study reported an unexplained 11% annual incidence of transient suspension of detection.151 This problem is addressed in Medtronic ICDs with an audible patient alert that sounds if programmed detection or therapy is “off ” for longer than 6 hours. VENTRICULAR TACHYCARDIA SLOWER THAN PROGRAMMED DETECTION INTERVAL In most ICD patients, VT with cycle lengths greater than 400 to 450 msec are tolerated well, but repeated inappropriate therapies are not. SVT-VT discrimination algorithms, except those in Sorin models,71,134,152 deliver fewer inappropriate therapies if the VT detection interval is programmed to a shorter cycle length, simply because fewer SVTs are evaluated. However, slow VT can be catastrophic in patients with severe LV dysfunction or ischemia,153 and a long VT detection interval is important in some patients with advanced heart failure (Fig. 3-83). The VT detection interval should be increased if antiarrhythmic drug therapy is initiated, particularly with amiodarone or a sodium channel–blocking (type IA or IC) drug.15 It may be prudent to measure the cycle length of induced VT at electrophysiologic testing after initiation of drug therapy.154 However, spontaneous VT often is slower than induced VT.155 SVT-VT DISCRIMINATORS The SVT-VT discriminators may prevent or delay therapy if they misclassify VT or VF as SVT.114,116,119,156 Discriminators that reevaluate the rhythm diagnosis during an ongoing tachycardia (e.g., stability, most dual-chamber algorithms) reduce the risk of underdetection of VT compared with discriminators that withhold therapy if the rhythm is

not classified correctly by the initial evaluation (e.g., onset, chamber of origin algorithms). The minimum cycle length for SVT-VT discrimination should be set to prevent clinically significant delay in detection of hemodynamically unstable VT. PACEMAKER-ICD INTERACTIONS Interactions between ICDs and separate pacemakers have become rare since ICDs incorporated dual-chamber bradycardia pacing. Potential interactions have been reviewed.157-159 The principal interaction that may delay or prevent ICD therapy is oversensing of high-amplitude pacemaker stimulus artifacts. If this occurs during VF, repetitive autoadjustment of sensitivity may prevent detection of VF. INTRADEVICE INTERACTIONS In intradevice interactions, bradycardia pacing features of dualchamber ICDs may interact with and impair detection of VT or VF.54 During high-rate, atrial or dual-chamber pacing, sensing may be restricted to short periods of the cardiac cycle because of the combined effects of ventricular blanking after ventricular pacing and crosschamber ventricular blanking after atrial pacing, which is needed to avoid crosstalk. If a sufficient fraction of the cardiac cycle is blanked, systematic undersensing of VT or VF may occur. When pacing and blanking events occur at intervals that are multiples of a VT/VF cycle length, ventricular complexes are repeatedly undersensed, delaying or preventing detection52-54 (Fig. 3-84). Intradevice interactions have been reported most frequently with the use of the rate-smoothing algorithm.52-54 This algorithm is intended to prevent VT/VF initiated by sudden changes in ventricular rate.160 Rate smoothing prevents sudden changes in ventricular rate by pacing both the atrium and the ventricle at intervals based on the preceding (baseline) R-R interval. As an unintended consequence, it may prevent sensing of VT/VF in some patients, because rate smoothing introduces

112

SECTION 1  Basic Principles of Device Therapy

Atrial EGM RV Coil-Can

Interval (ms) 1800 VF Detected

1720

3 5 0

A P T S

6 8 0

VV SP

4 2 0

V S

F F F F F F S S S S S S 2 1 1 2 1 1 1 8 2 0 2 6 0 0 0 0 0 0

4 6 0

V S

2 1 0

1600

A P

1760 F S

7 2 0

VV SP

4 7 0

V S

1 7 0

F S

4 7 0

V F S S 1 3 0

4 6 0

V S

2 1 0

F S

1 8 0

F S

1 8 0

F S

2 3 0

F S

2 2 0

F S

F F F F V V S S S S S S 2 1 1 1 4 2 5 3 8 8 4 0 0 0 0 0 0 0 VF Rx 1 Defib

5 1 0

V S

4 6 0

V S

1400 1200 1000

3.7 minutes

800 600

TDI

400

FDI 200 0 600

400

0

200

Time Before VF Detection (Seconds)

VF Detected

Figure 3-83  Ventricular tachycardia (VT) slower than the programmed detection interval. The lower panel is a “Flashback Interval” plot of R-R interval cycle lengths before detection of ventricular fibrillation (VF), which occurs at the right side of each panel. The interval number before detection is plotted on the abscissa, and the corresponding interval is plotted on the ordinate. Horizontal lines indicate the VT detection interval (TDI) of 400 msec and the VF detection interval (FDI) of 320 msec. Shortly after the 500th interval preceding detection, regular tachycardia begins abruptly. The constant cycle length indicates reliable ventricular sensing. Atrial flashback intervals (not shown) demonstrated atrioventricular (AV) dissociation. This VT is not detected despite reliable sensing, because the cycle length is greater than the programmed TDI. VT persists for 3.7 minutes until approximately interval 280 before detection, when sensed intervals become highly variable. This indicates degeneration of the rhythm to VF with undersensing that delays detection. During VT and VF, atrial Flashback Intervals (not shown) indicated lower rate limit bradycardia pacing at 40 bpm (1500 msec). The upper panel shows stored atrial and far-field ventricular EGMs immediately before detection with atrial and ventricular channel showing event markers. Specific undersensed EGMs cannot be identified because the rate-sensing EGM was not recorded. However, long sensed R-R intervals ending with ventricular sense (VS) markers indicate undersensing and correspond to long intervals in the upper panel. VF Rx 1 Defib at lower right (arrow) denotes “VF detected.” AP, Atrial paced event; FD, VF detected; FS, intervals in VF zone. (From Swerdlow C, Friedman P: Advanced ICD troubleshooting. Part I. Pacing Clin Electrophysiol 28:1322-1346, 2005.)

repetitive postpacing blanking periods. The algorithm applies rate smoothing to baseline intervals independent of their cycle length, including intervals in the VT or VF zones. Intradevice interactions that result in delayed or absent detection of VT/VF are most common and most dangerous when VT is fast. The parameter interrelationships that result in delayed or absent detection of VT/VF are complex and difficult to predict, but usually elicit a programmer warning. Generally, aggressive rate smoothing (a small, allowable percentage change in RR intervals), a high upper pacing rate, and a long and fixed AV interval favor undersensing and should be avoided. If rate smoothing is required, the AV delay should be dynamic, the upper rates should be 125 bpm or less, and parameter combinations that result in warnings should be avoided. This programming reduces, but does not eliminate, the risk of undersensing.52-54

Detection of SVT/VT as Diagnostic Tool and Basis for Atrial Antitachycardia Pacemakers and Atrial ICDs Detection of SVT and VT provides diagnostics that are useful for pacemaker management.161 Atrial antitachycardia pacing and shocks provide a therapeutic option for some patients with paroxysmal atrial

tachycardia/flutter (AT) and atrial fibrillation (AF). Appropriate delivery of this therapy requires accurate detection and discrimination AT and AF independent of ventricular rate. PACEMAKER DIAGNOSTICS Monitoring for Ventricular Tachycardia Some pacemakers have ventricular high-rate diagnostics that trigger EGM and marker storage of nonpaced rhythms that are faster than a specific rate. Triggers based on ventricular rate alone store episodes that may be rapidly conducted SVT, ventricular oversensing, or VT. Studies of these diagnostics demonstrate the importance of stored EGMs to confirm the diagnosis, because the false-positive detection rate is high.162 Newer dual-chamber pacemakers and antitachycardia pacemakers incorporate tachyarrhythmia detection algorithms that are identical or substantially similar to those in dual-chamber ICDs (Fig. 3-85). The performance of these algorithms may be influenced by differences in pacemaker and ICD atrial sensing characteristics (fixed atrial sensitivity, automatically adjusting sensitivity, or intermediate case) and atrial blanking periods (Fig. 3-86). Even with accurate atrial sensing, Bayes theorem predicts that the fraction of false-positive VT detection in patients with pacemakers is large, because the incidence of true VT is low.



3  Sensing and Detection

Surface ECG Atrial EGM Vent EGM

PABP VBP

AS 1875 VS 935

VP 350

VS 350

VP 350

VP 350

AP 863 VF 283 VF 280

AS 970

VP 350

VP 350

VP 350

Surface ECG Atrial EGM Vent EGM

25-FEB-00 19:30

AP 268 VP 560

VP 570

PVC 448

VP 230

VF 308

VT 415

AP 875

AP 723

VF 305

VP 560

AP 863 VF 283

AP 863 VS 575

VF 283

VF 285

AP 1118

VF 280

VP 570

VF 278

AP 860

AP 260 VP 560

VF 298

VF 285

VP 570

AP 850 VP 560

AP 1135

AP 865

VF 288

VP 580

GUIDANT

VP 570

VF 280

Surface ECG Atrial EGM Vent EGM

25-FEB-00 19:30

VENTAK PRIZM

VS 575

VF 283

VP 270

VP 250

Surface ECG Atrial EGM Vent EGM

25-FEB-00 19:30

AP 1630 VP 350

AP 863

AP 863 VF 293

25 mm/s

VENTAK PRIZM

VP 560

VF 280

113

AP 870 VF 300

AP 855 VF 275

AP 853 VS 573

VF 278

AP 858

AP 260

VF 283

AP 560

VF 788

VP 570

External rescue

AP 878 VP 570

VP 580

VF 298

AP 880 VF 290

AP 8737 VS 583

VF 288

VF 293

AP 260 [VS]

VP 560

[AS] (AS) 733 VF 308

Figure 3-84  Failure to detect ventricular tachycardia (VT) caused by intradevice interaction. The rate-smoothing algorithm introduced atrial and ventricular pacing complexes with associated blanking periods that prevented detection of VT during postimplantation testing. An external rescue shock was required. Top to bottom, Surface electrocardiogram (ECG), atrial EGM, ventricular EGM, and event markers. At top, VT is induced by programmed electrical stimulation with a drive cycle length of 350 msec and premature stimuli at 270, 250, and 230 msec (intervals labeled next to event markers). The first sensed ventricular event occurs 448 msec after the pacing drive (PVC 448). The rate-smoothing algorithm drives pacing to prevent a pause after the premature ventricular complex (PVC), labeled AP↓ 1638. A ventricular paced event does not follow the first AP↓ because a ventricular event is sensed (VT 415). Subsequent rate smoothing generated atrial and ventricular pacing pulses (indicated by AP↓ and VP↓ markers, respectively). The resultant postpacing blanking periods are shown on the figure as horizontal bars. PABP denotes cross-chamber (postatrial pacing) ventricular blanking period. VBP denotes same-chamber (postventricular pacing) blanking period. Together, they prevent approximately four of every six VT complexes from being sensed. Because the VT counter must accumulate 8 of 10 consecutive complexes in the VT zone for detection of VT to occur, VT is not detected. (From Swerdlow C, Friedman P: Advanced ICD troubleshooting. Part II. Pacing Clin Electrophysiol 29:70-96, 2006.)

V-V

A-A

VTM=400 ms

Interval (ms)

Detection

1500 1200 900 600

Term. 9 sec

AEGM VEGM

400 A P

200

230

225

220

215

210

Time (sec)

25

0

5

V S

0

A R

1180 5 6 0

1020

V 3 V 4 V S 7 S 5 S 0 0

6 9 0

9 8 0

A S

A R

9 4 0

A R

9 6 0

A R

9 2 0

A R

8 9 0

A R

8 7 0

A R

EGM for

V 5 V 3 V 3 V 3 V 3 V3 V 3 V3 V 3 V 3 V 3 V 3 V 3V 3 V 3 V3 V 3 V S 0 S 8 S 9 S 7 S 8 S3 S 4 S5 S 4 S 6 S 6 S 7 S 4S 6 S 9 S3 S 6 T 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VTM

A V-V

A-A

VTM=400 ms

Interval (ms)

Detection

1500 1200 900 600

Term. 1.4 min

AEGM

0.5mV

VEGM

400 .2000

200 230

225

220

215

210

Time (sec)

25

0

5

0

V S

5 6 0

V S

5 1 0

A b

.2000

A b

EGM for 1

V V V V V V V V V V V V V V V V V V S 4 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 T 1 7 8 7 9 8 7 7 6 8 7 9 5 0 0 8 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VTM

B Figure 3-85  Pacemaker diagnostics for monitoring of ventricular tachycardia (VT), showing stored intervals, atrial electrogrm (AEGM), ventricular electrogram (VEGM), and markers from a patient with a Medtronic EnRhythm DR pacemaker. The left panels show the A-A and V-V intervals plotted against time before VT detection, which requires 16 consecutive intervals at less than the VT monitoring interval of 400 msec (horizontal line). The right panels show dual-chamber EGM and markers. A, Onset of spontaneous VT occurs with several premature ventricular complexes (PVCs) and sudden acceleration of ventricular rate with little or no change in A-A intervals (left panel). The VT cycle length is initially 340 msec and progressively lengthens to greater than 400 msec after several seconds. After 8 consecutive intervals of 400 msec or longer, the ICD declares the episode to be “terminated” despite clear atrioventricular (AV) dissociation and ongoing VT (right-hand side of interval plot). The duration of VT is reported as 9 seconds, representing the time that the RR intervals remained less than 400 msec after initial detection. Dual-chamber EGM and markers leading up to detection of VT indicate appropriate sensing in both chambers and AV dissociation (right panel). B, Rapidly conducted atrial fibrillation with severe atrial undersensing reported as VT. The interval plot shows fast and irregular R-R intervals and long A-A intervals (1500 msec), with sporadic A-A intervals shorter than 200 msec. Dual-chamber EGMs indicate appropriate ventricular sensing but severe atrial undersensing of small-amplitude atrial fibrillation, resulting in false-positive detection of VT. AB, Atrial sensed event in postventricular atrial blanking period; AR, atrial refractory sense; AS, atrial sensed event; VS, ventricular sensed event; VT, VT detected.

114

SECTION 1  Basic Principles of Device Therapy

False-positive VT/VF episodes (%)

100%

80%

Patients with AT/AF history and no VT/VF history

60%

40%

20%

Secondary prevention ICD patient population

0% Higher incidence of true VT/VF relative to SVT Figure 3-86  Rate of inappropriate ventricular tachycardia/fibrillation (VT/VF) detection depends on the patient population. Bayes theorem predicts that patients with a higher incidence of true VT/VF relative to supraventricular tachycardia (SVT) will have fewer inappropriate detections than patients with a lower incidence of VT/VF. The receiver operator curve shows the Bayes theorem prediction of detection performance of an algorithm with a fixed sensitivity and specificity. The curve plots percentage of false-positive detections of VT/VF on the ordinate and estimated incidence of true VT/VF on abscissa. Two data points are plotted from clinical studies of two different patient populations with implanted ICDs running the same VT/SVT discrimination algorithm (Medtronic GEM DR68 and AT500 ICDs* with PR Logic). (*Willems R, Morck ML, Exner DV, et al: Ventricular high-rate episode in pacemaker diagnostics identify a high-risk subgroup of patients with tachy-brady syndrome. Heart Rhythm 1:414421, 2004.)

Monitoring for Atrial Tachycardia and Atrial Fibrillation Traditional pacemaker diagnostics for atrial high-rate episodes and automatic mode switches have been validated as a means of monitoring AT/AF.163,164 Diagnostic accuracy of these methods depends on the specific detection algorithm used and the accuracy of atrial sensing. Mode-switching algorithms and their diagnostics have been used as a surrogate marker for AT/AF detection in patients with dual-chamber pacemakers.161,163 A Holter monitoring study of 40 patients with bipolar pacemakers demonstrated that mode-switching diagnostics appropriately identified 53 of 54 true AT/AF episodes (98.1%) with only one short (13-second) false mode-switching episode.163 Other studies have reviewed stored pacemaker EGMs and found high percentages of inappropriate mode switching caused by atrial oversensing.162,165 Most modern pacemakers and ICDs store atrial EGMs for mode-switching events; and important clinical decisions, such as starting anticoagulation, should be based on analysis of atrial EGMs rather than mode-switching events. Further, absence of mode-switching events is not equivalent to absence of AT/AF in pacemakers with long PVAB periods or low atrial sensitivity. The AT/AF detection algorithms in some pacemakers and ICDs provide substantial additional information, including atrial EGMs, classification of AT versus AF, and integrated displays of data from multiple episodes. These include histograms of episode duration and ventricular rate during AT/AF that may be of value in managing atrial antiarrhythmic drugs and AV nodal blocking drugs (Fig. 3-87). The former histogram, combined with patient-activated ICD interrogations, may permit discontinuation of anticoagulation in some patients. A prospective study of 2486 patients with one or more stroke risk factors and an implantable pacemaker or ICD with continuous AT/AF monitoring evaluated the risk of thromboembolic events as a function of AT/AF burden (hours of AT/AF per day). More than 5.5 hours of AT/AF on any day doubled a patient’s risk of stroke.166 Other studies have demonstrated similar increased risk associated with monitored AT/AF episodes.166,167 Computer modeling predicts that home monitoring of patients with automatic ICD-generated alerts for detected AT/AF may reduce the risk of stroke.168 A multicenter randomized trial is designed to test the hypothesis that initiation and withdrawal of oral anticoagulation therapy guided by continuous AT/

AF monitoring reduces the risk of stroke, embolism and major bleeding compared with conventional management.169 DETECTION OF ATRIAL TACHYCARDIA AND ATRIAL FIBRILLATION Principles Bradycardia pacemakers must detect AT/AF rapidly so that mode switching will avoid uncomfortable pacing at the upper rate limit. To determine the atrial rate and rhythm accurately, atrial blanking must be minimized. As long as the atrial rate exceeds the upper tracking limit, accurate determination of atrial rate and rhythm is not important. Ventricular ICDs must discriminate VT from rapidly conducted AF quickly, to permit rapid detection of hemodynamically compromising VT. Discrimination of AT versus AF is less important. In contrast, atrial antiarrhythmic pacemakers and ICDs must detect AF with high specificity to minimize painful and potentially proarrhythmic therapy. Rapid detection is not important, because AF usually is clinically stable and may terminate spontaneously after hours to days. Therefore, atrial antiarrhythmic ICDs should be capable of permitting therapy for long-duration AT/AF while withholding therapy from self-terminating AT/AF. To achieve this goal, they must be capable of detecting AF continuously for extended periods, to discriminate between repetitive self-terminating episodes and persistent episodes. Because atrial EGMs in AF have low and variable amplitudes and slew rates, antiarrhythmic ICDs must have high (automatically adjusting) atrial sensitivity and apply algorithms that are tolerant of some atrial undersensing. They must also discriminate between AT and AF to deliver ATP for AT. Detection of AT/AF for Atrial Therapy High specificity in AT/AF detection has been achieved by multistep methods for detection of AT/AF. Initial detection is based on the presence of an atrial tachyarrhythmia and absence of VT. This is achieved by a measure of atrial rate combined with either comparison of atrial and ventricular rates (Boston Scientific)170 or use of A-V patterns to identify N:1 rhythms (Medtronic) (Fig. 3-88). The trade-off between atrial undersensing and oversensing of FFRWs that applies to dualchamber ICD algorithms is even more important when considering



115

3  Sensing and Detection VENTRICULAR RESPONSE (IN AF)

Long-term trends May 00

Jul 00

Program/interrogate

Sep 00

Nov 00

P

Drug change

Jan 01

Mar 01

P

# beats

May 01 I

Sotalol

CV/ablation/other AT/AF patient check AT/AF total hrs/day

AT/AF episodes/day

24 20 16 12 8 4 0 .25 20 15 10 5 0

ATP change

% ATP success

.25 20 15 10 5 0

% Pacing/day

(0%)

80-100 bpm

3

(0%)

100-120 bpm

124

(4%)

120-140 bpm

175

(6%)

140-160 bpm

344

(12%)

160-180 bpm

912

(33%)

180-200 bpm

880

(32%)

>200

319

(12%)

100

100 75 50 25 0

ATP ON 80

Antici-Pace Change % Pacing/day — A.total — A. ARS/APP

0

DATA - AT/AF EPISODE DURATION HISTOGRAM

Episodes (%)

Treated AT/AF episodes/day



Episode duration

Figure 3-87  Diagnostic data stored in atrial antiarrhythmic pacemakers and ICDs assist medical management of atrial arrhythmias. Data are taken from three patients with Medtronic AT500 pacemakers. Left panels, Long-term trend data over 1 year. Panels from top to bottom show total hours per day in atrial tachycardia/flutter (AT) or atrial fibrillation (AF), total AT/AF ICD-detected episodes per day, number of daily episodes treated by antitachycardia pacing (ATP), percentage of ATP therapies classified as “successful” by the ICD, percent atrial pacing, and percent ventricular pacing. ATP ON denotes activation of atrial ATP. Note that, although the many episodes of AT/AF are treated and this treatment is usually classified as successful, there is no detectable change in the number of hours per day of AT/AF until sotalol therapy is initiated. Sotalol decreases the total hourly “burden” of AT/AF more by shortening episodes rather than by preventing them. Percent ventricular pacing is high throughout but increases after sotalol treatment to almost 100%. Top right panel, Ventricular rate during AT/AF as percentage of time spent in AT/ AF; 77% of intervals are shorter than intervals corresponding to 160 bpm, and 12% are shorter than intervals corresponding to 200 bpm, indicating inadequate control of ventricular rate. Lower right panel, Histogram of durations of AT/AF episodes since the last follow-up visit. This patient had 10 episodes of AF since the last visit, but only one episode lasted longer than 10 minutes.

detection of AT/AF for atrial therapy. Minimization of atrial blanking is important to prevent undersensing of AF, and rejection of FFRWs is important to prevent inappropriate detection of AT/AF (see earlier Atrial Sensing in Dual-Chamber ICDs and Atrial ICDs). Once initial detection occurs, the episode timer begins, initiating a sustained-detection mode in which AT/AF remains detected despite a moderate degree of undersensing (Fig. 3-89). When this timer expires, atrial therapy is delivered if AT/AF still persists (Fig. 3-90). Atrial episodes must be interrupted if true VT occurs. The final step in detection is discrimination of AT from AF or, alternatively, determining whether the rhythm is likely to respond to atrial ATP. As shown in Figure 3-88, Medtronic atrial ICDs track dynamic changes in atrial tachyarrhythmia (e.g., transitions between AT and AF) based on the median rate and regularity of the atrial rhythm. Boston Scientific atrial ICDs use a more complex algorithm based on maximum rate, standard deviation, and range of the 12 most recent atrial cycle lengths to plot a point in a three-dimensional space. A decision boundary divides the space into two regions: faster/irregular

atrial cycle lengths (AF) and slower/regular cycle lengths (AT). Classifications are made on a sliding window of 12 consecutive cycles until the end of the episode is reached.170,171 Typically, there may be one timer for ATP and one for shock therapy. In newer Medtronic ICDs, the “reactive antitachycardia pacing” algorithm resets the ATP timer to permit repeat attempts at ATP if changes in atrial rate or atrial rhythm regularity are detected, or after a preprogrammed duration of sustained AT/AF. Changes in rate or regularity of the atrial rhythm are classified as a shift to a new rhythm, which may be more susceptible to ATP termination (Fig. 3-91). Detection Considerations for Atrial Shocks In addition to permitting therapy after hours of continuous AF, atrial ICDs may withhold therapy if the episode duration is sufficiently long that patients may be at risk for thromboembolism if they are not adequately anticoagulated, typically 24 hours. R-wave-synchronized atrial shock therapy is restricted to R-R intervals greater than 400 to 500 msec. This minimizes the risk that a therapeutic atrial shock can

116

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Median P-P interval

Auto discrimination zone

AF detection zone

Atrial blanking (100 mS)

AFDI: 280 mS AFDI: 320 mS

ATDImin: 180 mS AT detection zone

AF/AT evidence counter

Atrial fibrillation

P R

A

B

D Count: +1 Count: 28

+1 29

+1 30

A=A range

−1 29

+1 30

+1 31

+1 32

SD

Figure 3-88  Criteria for detection of atrial tachyarrhythmias. A, Medtronic atrial therapy ICDs (Jewel AF, GEM III AT, AT500, and EnRhythm DR) use a combination of atrial cycle length and atrial/ventricular (A : V) patterns to detect atrial fibrillation and atrial flutter. The atrial tachycardia (AT) and atrial fibrillation (AF) detection zones are based on median atrial cycle length (12 P-P intervals) and may overlap. The overlap region is the “autodiscrimination” zone, where regularity of the PP intervals determines whether rhythm classification is AT (regular P-P intervals) or AF (irregular P-P intervals). Detection of AT or AF requires that (1) the median P-P interval is in one of the detection zones and (2) the rhythm is N:1 as determined by the AF/AT evidence counter. The AF/AT evidence counter is an up-down counter (minimum value, 0; maximum value of detection threshold, +15). The counter increments by 1 on each ventricular event if there are two or more atrial events and there is no pattern-based evidence of far-field R-wave oversensing on the atrial channel (see Fig. 3-25, A), and it decrements by 1 if there is strong evidence of lack of N:1 rhythm (e.g., two consecutive 1 : 1 beats). Isolated 1 : 1 beats contribute AF/AT evidence if they are preceded by a confirmed N:1 beat. The AF/AT counter detection threshold is between 24 and 32, depending on the specific ICD. AFDI, Atrial fibrillation detection interval; mS, milliseconds. B, Atrial Rhythm Classification (ARC) algorithm (Boston Scientific) discriminates AF from atrial flutter (AFL) based on the atrial rate and two measurements of variability of atrial rate: the range of the atrial intervals (i.e., the difference between the longest and shortest A-A intervals [A-A range]) and the standard deviation of A-A intervals (SD). The values of these three variables define a point in a three-dimensional space. A curved surface separates the AF region from the AFL region. Points in the AF region have higher atrial rates, a higher range of A-A intervals, and a greater standard deviation of A-A intervals. (From Morris MM, KenKnight BH, Lang DJ: Detection of atrial arrhythmia for cardiac rhythm management by implantable ICDs. J Electrocardiol 33(Suppl):133-139, 2000.)

be delivered into the vulnerable period of the preceding cardiac cycle, but it may prevent shock therapy for rapidly conducted AF. Early or immediate recurrence of AF after shock is an important clinical problem in patients with atrial ICDs. Early recurrence of AF before postshock redetection of sinus rhythm will result in incorrect classification of shock success (Fig. 3-92).

Sensing and Detection Using the Subcutaneous Electrocardiogram IMPLANTABLE SUBCUTANEOUS MONITORING Implantable loop recorders (ILRs) offer patient-activated recordings of subcutaneous ECGs as well as arrhythmia detection algorithms to automatically trigger storage for asystole, bradycardia/tachycardia, and AF. Two sensing electrodes are built into the ILR shell and record a single-lead bipolar ECG that is retrieved with a programmer or remote-monitoring ICD. ECG signals are stored in a circular buffer. Multiple, automatically triggered events may be stored. The memory buffer may also be activated by a hand-held system to record the ECG preceding and following activation. Automated triggers for storage of arrhythmic events in ILRs require robust R-wave sensing and detection algorithms based on RR intervals. The amplitude of R waves recorded by an ILR averages about 0.3 mV, versus 1 to 2 mV recorded in the precordial leads of a surface ECG.

Unlike EGMs, the amplitude of subcutaneous ECGs increases over time to about 0.35 mV at 4 to 6 months, then remains stable.172 R-wave sensing in an ILR uses the same principles as shown in Figure 3-13 with band-pass filtering tuned for lower frequencies and either fixed or auto-adjusting sensitivity. Sensing problems were common with early models that used a fixed sensing threshold, including undersensing caused by abrupt, unexplained decreases in R-wave amplitude and ICD amplifier saturation, as well as oversensing of T waves, myopotentials, and other sources of noise.173-175 Sensing enhancements such as better noise rejection and auto-adjusting threshold reduce both false-positive triggers caused by oversensing and problems related to undersensing.176 Figures 3-93 and 3-94 show examples of rhythms recorded by ILRs. Monitoring of AF burden has been a recent addition to the Medtronic Reveal XT ILRs. The algorithm detects the irregularly irregular ventricular response to conducted AF by analyzing the difference between the present and previous R-R intervals (δRR). Pattern analysis is performed using Lorenz plots, or scatter plots of δRR(i) vs. δRR(i-1) over a duration of 2 minutes.177 The algorithm can distinguish patterns associated with AF and regular AT from sinus rhythm, as shown in Figure 3-95. This algorithm was shown to have sensitivity of 96.1% and specificity of 85.4% for identifying patients with or without AF in a study of 247 patients using Holter ECGs as a “gold standard.”178 AF burden as measured by this algorithm was highly correlated with the Holter standard.



3  Sensing and Detection 13:26:26-1

117

AF - - MS delta

ECG

AEGM

AP

AP

AR FS FS FS FS FS

FS FS FS FS FS FS FS FS FD FD FD

Marker VP PP Median Atrial Evidence

VP 750 0

VS 750 1

VP 750 2

VS 200 30

VP 200 31

VP 210

VP 210 *A

A

ECG

AEGM 1 sec Marker

FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD VS VS PP Median Atrial Evidence

VS 170

VS 170

VP 170

VS 180 *A

FD FDFDFD FD FDFD FD FD FD FD VP 170

VS 170

VS 170

VS 170 *A

B Figure 3-89  Holter recording illustrates continuous detection of atrial fibrillation (AF). A, Onset of AF and initial detection of AF after 32 ventricular events (arrow). Double atrial markers (FS) change to triple markers (FD), and the symbol *A appears on the atrial evidence channel to indicate AF episode in progress. B, Rhythms after 5 hours of continuous recording. AP, Atrial paced event; VP, ventricular paced event; VS, sensed R wave. (From Swerdlow CD, Schsls W, Dijkman B, et al: Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverterdefibrillator. For the Worldwide Jewel AF Investigators. Circulation 101:878-885.)

SUBCUTANEOUS ICDS Investigational subcutaneous ICD (S-ICD) systems, with no transvenous or epicardial leads, are undergoing clinical trials. They rely on subcutaneous ECGs for sensing and detection of VF. The present S-ICD (Cameron Health) uses a 69-cc pulse generator placed in the left midaxillary line over the lower thorax. A single subcutaneous lead is tunneled medially to the left parasternal position and then superiorly along the sternum. It includes two widely spaced sensing electrodes and a defibrillation coil (Fig. 3-96). Sensing The S-ICD automatically selects the best sensing vector based on QRS amplitude and signal-to-noise ratio from among three choices: (1) proximal electrode ring on the lead to the active surface of the pulse generator, (2) distal electrode ring on the lead to the pulse generator, or (3) distal ring to proximal ring. The S-ICD automatically selects one of two amplifier gains (±2 mV unless QRS amplitude is clipped at this setting; otherwise, ±4 mV) and the sensing vector least likely to oversense T waves (Fig. 3-97; see also Fig. 3-96). As in ICDs with intracardiac leads, the S-ICD uses automatic adjustment of sensitivity. Sensitivity increases when rapid rates are detected. In addition to this event detection phase of sensing, the S-ICD has a certification phase that examines sensed events and classifies them as certified QRS complexes or as suspect events. This ensures that accurate ventricular rate is passed to the detection algorithm. An event is

classified as “suspect” if its pattern or timing suggests oversensing, according to specific oversensing rules intended to reject myopotentials, R-wave double-counting, and T-wave oversensing. Sensing and Tachyarrhythmia Detection The detection algorithm (decision phase) examines all certified events and calculates a continuous, running, “four R-to-R interval average” (4 RR average), which is used as a measure of ventricular rate. Rate-based therapy zones include a mandatory rate-only VF (“shock”) zone and an optional VT (“conditional”) zone. In the VT zone the S-ICD uses stable QRS morphology and QRS width to discriminate VT from SVT, as well as varying QRS morphology to identify polymorphic VT. The “START” study compared SVT-VT discrimination using tachyarrhythmias recorded at ICD or S-ICD implant.124 The S-ICD detection algorithm had equivalent sensitivity for VT to the best ICD algorithm (100%), and insignificantly better specificity for rejection of SVT (100% vs. 92%). The S-ICD detection process begins when the “4 RR average” enters either therapy zone. VT or VF detection is a two-step process. The initial detection step uses X of Y counting (18/24 for the first therapy), and the “persistence” step requires that the X of Y criterion remain fulfilled for additional consecutive intervals (nominally two, but automatically increased if shocks are aborted). Capacitor charging begins if persistence is met and if the last two certified sensed events are in a therapy zone. Shock confirmation, redetection, and episode termination function similar to these features in ICDs with intracardiac leads.

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SECTION 1  Basic Principles of Device Therapy

Onset

Detection 12 sec

First Rx

Termination 19 sec

1 min

Marker 5 0 0

P P

2 1 1 1 1 1 1 1 1 7 9 8 9 9 8 9 7 9 A 0 T 0 T0 T 0 T0 T 0 T0 T0F0 T R S F F F F F F S F

V P

220

210

0

230

220

Time (sec)

210

V S

4 4 0

0

V S

4 1 0

T S

3 5 0

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3 7 0

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T S

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Onset

Atip-Vring EGM

Marker

1 2 1 1 1 1 1 1 1 2 2 1 1 2 1 1 2 1 2 1 1 1 1 1 1 2 2 2 8 1 9 9 9 9 9 8 7 1 0 9 9 0 9 9 0 9 0 8 7 6 5 5 5 6 2 2 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 A 0 A 0 A 0 A 0 A0 A 0 A 0 T 0 T 0 T D D D D D D D D D D D D D D D D D D D S P P P P P P S F F V S

4 4 0

6 0 0

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4 4 0

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5 5 0

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6 2 0

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6 2 0

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4 8 0

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4 3 0

First Rx

V S

4 1 0

3 4 0

V S

4 9 0

6 7 0

A P V P

6 0 0

6 6 0

A P 5 9 0

A P

V S

V P

7 4 0

Figure 3-90  Atrial tachycardia (AT) detection and therapy after 1 minute of sustained detection. Spontaneous episode of AT from an atrial therapy ICD. Upper left panel, P-P intervals (open squares) and R-R intervals (closed circles) for this episode. Onset of the AT episode is labeled on the interval plot and on the stored marker channel (top right). The interval plot also labels the initial detection of AT (Detection), delivery of the first therapy (First ATP Rx), and ICD recognition of episode termination (Termination). In this case, therapies were programmed to begin 1 minute after initial detection. Top right panel, Dual-chamber EGM markers preceding detection of AT. Dots indicate discontinuous recording between top and bottom panels. Bottom panel, Composite EGM recorded between the atrial tip electrode (Atip) and the ventricular ring electrode (Vring) and dualchamber EGM markers immediately preceding delivery of successful antitachycardia pacing (First Rx, fast AP events). TS, FS, and TF events refer to atrial intervals in the AT, atrial fibrillation (AF), and overlap zones, respectively. TD (atrial marker), Atrial tachycardia detected; VP, ventricular paced event; VS, ventricular sensed event.

2 2 0

T D

2 1 0

T D

V S

2 1 0

T D

2 1 0

T D

2 1 0

2 1 0

T D

T D

V S

8 1 0

2 3 0

T D

2 4 0

2 5 0

T D

T D

2 4 0

V S

9 4 0

T D

2 3 0

T D

2 2 0

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2 1 0

T D

V S

7 9 0

2 1 0

T D

2 2 0

T D

2 2 0

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6 6 0

T D

2 2 0

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6 8 0

Successful atrial ATP 3 7 0

T S V S

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7 5 0

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T S

7 6 0

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7 7 0

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3 2 0

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3 1 0

7 4 0

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7 5 0

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2 6 0

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1 0 0

6 3 0

1373

A S V S

6 0 0

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1 0 0

A P

9 0 0

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1 0 0

A P

9 8 0

V P

Figure 3-91  Example of successfully terminated atrial tachycardia/fibrillation (AT/AF). Top panel, Atrial EGM and marker diagram from AT/ AF episode (median atrial interval, 220 msec) that was initially detected and treated unsuccessfully with antitachycardia therapy (ATP). Bottom panel, After 2.1 hours, the atrial rate slowed, and the reactive ATP algorithm recognized the presence of a slower, regular AT/AF rhythm with a median atrial interval of 370 msec. Atrial ATP was delivered and successfully terminated the AT/AF. AP, atrial paced event; TD, AT/AF detected; TS, AT/AF sensed event; VP, ventricular paced event; VS, ventricular sensed event. (From Mainardi L, Sornmo L, Cerutti S: Understanding atrial fibrillation: the signal processing contribution, San Rafael, Calif, 2008, Morgan & Claypool.)



3  Sensing and Detection

119

Lead II

Shock

Atip-Aring

ERAF

Markers A A A A AAA R R S R S RS

V S

V S

V C V S E S

A A A AC S S S SD

V R

A S

A S

V P

V S

A S

V S

A A A R R R

V S

V S

A A A A A A AAAA A AA R R RS R RSRSR S RR

V S

V S

V S

V P

V S

V S

V P

Figure 3-92  Postshock early recurrence of atrial fibrillation (ERAF) recorded at implantation occurs three RR intervals after shock. Because the ICD requires five consecutive postshock beats of sinus or atrial paced rhythm to detect termination of atrial fibrillation (AF) and store intervals, no data were stored for this clinically unsuccessful shock. Lead II of the surface electrocardiogram, the atrial EGM, and the atrial and ventricular channels with event markers are shown. AR, Atrial refractory event; AS, atrial sensed event; CD, charge delivered; CE, charge end; VP, ventricular paced event, VS, ventricular sensed event. (From Swerdlow CD, Schwartzman D, Hoyt R, et al: Determinants of first-shock success for atrial implantable cardioverter defibrillators. J Cardiovasc Electrophysiol 13:347-354, 2002.)

11:32:07

11:32:20

11:32:33

11:32:46

11:32:59

Figure 3-93  Stored EGM recorded by an implantable loop recorder (Reveal, Medtronic) shows about 45 seconds of asystole, some myopotentials, perhaps one depolarization in the middle of the asystole, very small deflections throughout that are probably P waves, and relative bradycardia on the bottom panel. The amplitude of the subcutaneous electrocardiogram is approximately 0.25 mV.

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12:22:47 P

12:23:00

230 bpm (260 msec) Figure 3-94  Stored EGM recorded by an implantable loop recorder (Reveal, Medtronic) shows nonsustained tachycardia at about 230 bpm with duration of 8 seconds. The underlying rhythm is reset by the high-rate segment. The patient did activate this stored strip, as indicated by the dark triangle and the “P” marker.

RR 670 435 900 520 800 1030 700 675 760 650 515 625 925 δRR

−235 525 −440 280 250 −350 −25 85 −110 −135 110 300

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3 4 5 6 7 δRR(i-1) (msec)

8

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5 8

11

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δRR(i) (msec)

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1

B Figure 3-95  Algorithm for detection of atrial fibrillation (AF) by implantable loop recorder based on pattern of R-R intervals. A, Illustration showing how R-R intervals derived from a short strip of subcutaneous ECG during AF populate the numerical equivalent of a Lorenz plot of ΔRR intervals. Each point in the Lorenz plot is derived from four R waves that provide three R-R intervals and thus a [δRR(i), δRR(i-1)] value. The markers near the top of each R wave indicate the time at which each R wave is sensed. The magnitude of the vector from the origin of the Lorenz plot to each point encodes the irregularity, and the magnitude coupled with phase encodes the incoherence, of changes in R-R intervals. B, ECG tracings (2-minute duration) of AF (top panel), two examples of atrial flutter (middle and bottom panels), and the corresponding patterns they map to in a Lorenz plot of δRR intervals (right-hand side of each tracing). Note that a collection of δRR intervals on the Lorentz plot during atrial fibrillation/ flutter results in characteristic signatures, including the clustering of points for periods of regularity. These signatures form the basis for the detection/ discrimination algorithm.



3  Sensing and Detection

QRS: T wave: Ratio:

QRS: T wave: Ratio:

1.6 mV 0.4 mV 4

QRS: T wave: Ratio:

0.9 mV 0.1 mV 9

121

1.6 mV 1.0 mV 1.6

Figure 3-96  Electrode system for subcutaneous ICD (S-ICD).

Future Directions: Hemodynamic Sensors for ICDs Current ICDs do not differentiate directly between hemodynamically stable and unstable tachycardias. Morbidity associated with unnecessary shocks for hemodynamically stable VT and repetitive shocks caused by SVT may be reduced using implantable hemodynamic sensors integrated in the therapy decision process. Mixed-venous oxygen saturation, right atrial pressure, RV pressure, subcutaneous photoplethysmography, endocardial accelerometers, and cardiac impedance sensors have been proposed as methods of discriminating hemodynamically stable from unstable tachycardias.57,179-183 Subcutaneous photoplethysmography has been tested in acute and chronic animal models as well as acute human studies. There is a good

correlation between mean arterial pressure and photoplethysmography pulse amplitude; discriminating perfusing (stable) from nonperfusing (unstable) tachycardias is feasible169,184 (Fig. 3-98). An implantable system for ambulatory hemodynamic monitoring using RV pressure has been studied in clinical trials.185 A recent clinical trial studied an ICD with the capability of recording RV pressure waveforms during tachycardias detected using “rate + interval” analysis. Episodes of recorded spontaneous VT-VF demonstrate substantial changes in RV pressure waveforms (Fig. 3-99). Although this clinical trial was terminated because of an unacceptable failure rate of the pressure sensor, it provided valuable data to assist in developing metrics that discriminate hemodynamically stable versus hemodynamically unstable tachyarrhythmias for integration into ICD algorithms.186

Amp mV1

3 0

3 0

0.05

0.1

0.35

0.4

0.15 Time

0.2

0.25

0.3

Amp mV2

3 0

3 0.3

0.45 0.5 0.55 0.6 Time Figure 3-97  Automatic selection of best sensing vector for subcutaneous ICD (S-ICD). The potential sensing vectors for S-ICD are shown. The S-ICD uses the ratio of R-wave amplitude to T-wave amplitude to choose the optimal sensing vector.

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SECTION 1  Basic Principles of Device Therapy

O2 index

Pressure (mm Hg)

ECG (mV)

1 0.5

LED

0

Photodiode

–0.5 200

LED

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O2 index

Pressure (mm Hg)

ECG (mV)

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1.5 1 0.5 0 –0.5 –1 –1.5 200 150 100 50 0 0.02 0 –0.02 –0.04 0

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10 12 Time (sec)

14

16

18

20

Figure 3-98  Recordings from investigational sensor during electrophysiology laboratory testing. The sensor is mounted on the housing of an ICD emulator placed in the pocket during implant testing. Inset shows light-emitting diodes (LED) and light-receiving photodiode on housing of ICD emulator. Each panel shows surface ECG (upper tracing), arterial pressure (middle tracing), and photoplethysmographic oxygen (O2) index of tissue perfusion (lower tracing). The first panel shows the onset of atrial pacing at cycle length 400 msec. The arterial pressure remains stable, and the O2 index retains its phasic component with a mean value near the baseline-normalized value of zero. The second panel shows the onset of VF induced by 50-Hz current. With the onset of 50-Hz stimulation, the arterial pressure drops abruptly, and the O2 index loses its phasic component. About 2 seconds later, the O2 index begins a steep, monotonic decline. (Modified from Kroll MW, Swerdlow CD: The future of the implantable defibrillator. In Efimov I, Kroll M, Tchou P, editors: Cardiac bioelectric therapy: mechanisms and practical implications, Berlin, 2008, Springer Verlag.)



3  Sensing and Detection

123

RV pressure (mm Hg)

100

A

80 VS

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578

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VS VS TS TF TF TS TF TF TS TF TF TF TF TF TF TF TF TF TF TF T 438 328 313 297 344 313 313 344 297 313 313 297 297 297 297 297 313 297 297 313

40 20 0

VT no syncope

RV pressure (mm Hg)

100

B

80 60

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625

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703

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625

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703

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750

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719

484

516

VS TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TFT

297 266 266 266 266 250 266 250250 266 250 266250250 250 266234 250 250

40 20 0

VT syncope

RV pressure (mm Hg)

100

C

80 VS VS VS VS VS TF VS VS VS VS VS VSTF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TFTPTP TPTP 60 VS 375 375 391 375 375 250 469 391 375 391 375 375 266 250 266 250 266266 266 266 250 266266266 201 266 266 266 266 234 219 234 234

40 20 0

Rapidly-conducted AF 0

1

2

3

4

5

6

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10

Figure 3-99  Stored EGM and pressure tracing from investigational ICD with hemodynamic sensor (Medtronic Chronicle ICD). In each panel, the upper tracing shows the shock electrogram recorded between right ventricular (RV) coil and left pectoral ICD housing. The marker channel below it shows interval classification and interval duration in milliseconds. The lower tracing shows RV pressure recorded from the implanted hemodynamic sensor in mm Hg. Horizontal axis shows time in seconds. Intervals are labeled VS (sinus zone), TS (VT zone), and TF (fast VT zone). A, Onset of VT at cycle length 300 msec. The patient was asymptomatic prior to antitachycardia pacing. RV systolic pressure falls by less than half. B, Onset of VT at cycle length 250 msec. The patient presented with syncope. RV systolic pressure drops abruptly and remains below a third of the baseline value. C, Rapidly conducted atrial fibrillation at cycle length 260 msec. Inappropriate antitachycardia pacing (TP markers) occurs for the last four beats. There is only a slight reduction in RV systolic pressure at shorter cycle lengths. The patient had no alteration of consciousness. (Tracings courtesy Dr. Michael Sweeney. From Kroll MW, Swerdlow CD: The future of the implantable defibrillator. In Efimov I, Kroll M, Tchou P, editors: Cardiac bioelectric therapy: mechanisms and practical implications, Berlin, 2008, Springer Verlag.)

REFERENCES 1. Parsonnet V, Myers GH, Kresh YM: Characteristics of intracardiac electrograms. II. Atrial endocardial electrograms. Pacing Clin Electrophysiol 3:406-417, 1980. 2. Saxonhouse SJ, Conti JB, Curtis AB: Current of injury predicts adequate active lead fixation in permanent pacemaker/ defibrillation leads. J Am Coll Cardiol 45:412-417, 2005. 3. Sweeney MO, Ellison KE, Shea JB, Newell JB: Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverter defibrillators. J Cardiovasc Electrophysiol 12:402-410, 2001. 4. Weretka S, Michaelsen J, Becker R, et al: Ventricular oversensing: a study of 101 patients implanted with dual chamber defibrillators and two different lead systems. Pacing Clin Electrophysiol 26:65-70, 2003. 5. Cao J, Koyrakh L, Gillberg J, et al: A new automatic electrogram template updating algorithm: enhancing VT/SVT discrimination in ICDs. Pacing Clin Electrophysiol 24:706, 2001. 6. Platia EV, Brinker JA: Time course of transvenous pacemaker stimulation impedance, capture threshold, and electrogram amplitude. Pacing Clin Electrophysiol 9:620-625, 1986.

7. DeCaprio V, Hurzeler P, Furman S: A comparison of unipolar and bipolar electrograms for cardiac pacemaker sensing. Circulation 56:750-755, 1977. 8. Cornacchia D, Jacopi F, Fabbri M, Finzi C: [Comparison between active screw type and passive electrodes in permanent intraventricular pacing]. Minerva Cardioangiol 32:101-103, 1984. 9. Ceviz N, Celiker A, Kucukosmanoglu O, et al: Comparison of mid-term clinical experience with steroid-eluting active and passive fixation ventricular electrodes in children. Pacing Clin Electrophysiol 23:1245-1249, 2000. 10. Danilovic D, Ohm OJ: Pacing impedance variability in tined steroid eluting leads. Pacing Clin Electrophysiol 21:1356-1363, 1998. 11. Hua W, Mond HG, Strathmore N: Chronic steroid-eluting lead performance: a comparison of atrial and ventricular pacing. Pacing Clin Electrophysiol 20:17-24, 1997. 12. Crossley GH, Brinker JA, Reynolds D, et al: Steroid elution improves the stimulation threshold in an active-fixation atrial permanent pacing lead: a randomized, controlled study. Model 4068 Investigators. Circulation 92:2935-2939, 1995.

13. Wish M, Swartz J, Cohen A, et al: Steroid-tipped leads versus porous platinum permanent pacemaker leads: a controlled study. Pacing Clin Electrophysiol 13:1887-1890, 1990. 14. Ellenbogen KA, Wood MA, Gilligan DM: Evaluation of “inappropriate” ICD shocks in an asymptomatic patient following myocardial infarction. Pacing Clin Electrophysiol 19:254-255, 1996. 15. Goldschlager N, Epstein A, Friedman P, et al: Environmental and drug effects on patients with pacemakers and implantable cardioverter/defibrillators: a practical guide to patient treatment. Arch Intern Med 161:649-655, 2001. 16. Rajawat YS, Patel VV, Gerstenfeld EP, et al: Advantages and pitfalls of combining device-based and pharmacologic therapies for the treatment of ventricular arrhythmias: observations from a tertiary referral center. Pacing Clin Electrophysiol 27:1670-1681, 2004. 17. Theres H, Stadler RW, Stylos L, et al: Comparison of electrocardiogram and intrathoracic electrogram signals for detection of ischemic ST segment changes during normal sinus and ventricular paced rhythms. J Cardiovasc Electrophysiol 13:990-995, 2002.

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SECTION 1  Basic Principles of Device Therapy

18. Centurion OA, Isomoto S, Shimizu A, et al: The effects of aging on atrial endocardial electrograms in patients with paroxysmal atrial fibrillation. Clin Cardiol 26:435-438, 2003. 19. Frohlig G, Schwerdt H, Schieffer H, Bette L: Atrial signal variations and pacemaker malsensing during exercise: a study in the time and frequency domain. J Am Coll Cardiol 11:806-813, 1988. 20. Ross BA, Zeigler V, Zinner A, et al: The effect of exercise on the atrial electrogram voltage in young patients. Pacing Clin Electrophysiol 14:2092-2097, 1991. 21. Schuchert A, Kuck KH, Bleifeld W: Stability of pacing threshold, impedance, and R wave amplitude at rest and during exercise. Pacing Clin Electrophysiol 13:1602-1608, 1990. 22. Shandling AH, Florio J, Castellanet MJ, et al: Physical determinants of the endocardial P wave. Pacing Clin Electrophysiol 13:1585-1589, 1990. 23. 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Karagueuzian HS, Khan SS, Peters W, et al: Nonhomogeneous local atrial activity during acute atrial fibrillation: spectral and dynamic analysis. Pacing Clin Electrophysiol 13:1937-1942, 1990. 39. Lewalter T, Schimpf R, Kulik D, et al: Comparison of spontaneous atrial fibrillation electrogram potentials with the P-wave electrogram amplitude in dual chamber pacing with unipolar atrial sensing. Europace 2:136-140, 2000. 40. Ropella KM, Sahakian AV, Baerman JM, Swiryn S: Effects of procainamide on intra-atrial [corrected] electrograms during atrial fibrillation: implications [corrected] for detection algorithms. Circulation 77:1047-1054, 1988. 41. Bellardine Black CL, Stromberg K, van Balen GP, et al: Is surface ECG a useful surrogate for subcutaneous ECG? Pacing Clin Electrophysiol 33:135-145, 2010. 42. Van Dam P, van Groeningen C, Houben RP, Hampton DR: Improving sensing and detection performance in subcutaneous monitors. J Electrocardiol 42:580-583, 2009. 43. Beeman AL, Deutsch G, Rea RF: Paradoxical undersensing due to quiet timer blanking. Heart Rhythm 1:345-347, 2004. 44. Willems R, Holemans P, Ector H, et al: Paradoxical undersensing at a high sensitivity in dual chamber pacemakers. Pacing Clin Electrophysiol 24:308-315, 2001. 45. Castro A, Liebold A, Vincente J, et al: Evaluation of autosensing as an automatic means of maintaining a 2:1 sensing safety margin in an implanted pacemaker. Autosensing Investigation Team. Pacing Clin Electrophysiol 19:1708-1713, 1996. 46. Nowak B, Kampmann C, Schmid FX, et al: Pacemaker therapy in premature children with high degree AV block. Pacing Clin Electrophysiol 21:2695-2698, 1998. 47. Inama G, Santini M, Padeletti L, et al: Far-field R wave oversensing in dual chamber pacemakers designed for atrial arrhythmia

management: effect of pacing site and lead tip to ring distance. Pacing Clin Electrophysiol 27:1221-1230, 2004. 48. Dekker LR, Schrama TA, Steinmetz FH, Tukkie R: Undersensing of VF in a patient with optimal R wave sensing during sinus rhythm. Pacing Clin Electrophysiol 27:833-834, 2004. 49. Callans DJ, Hook BG, Kleiman RB, et al: Unique sensing errors in third-generation implantable cardioverter-defibrillators. J Am Coll Cardiol 22:1135-1140, 1993. 50. Callans DJ, Hook BG, Marchlinski FE: Paced beats following single nonsensed complexes in a “codependent” cardioverterdefibrillator and bradycardia pacing system: potential for ventricular tachycardia induction. Pacing Clin Electrophysiol 14:1281-1287, 1991. 51. Callans DJ, Hook BG, Marchlinski FE: Effect of rate and coupling interval on endocardial R wave amplitude variability in permanent ventricular sensing lead systems. J Am Coll Cardiol 22:746-750, 1993. 52. Glikson M, Beeman AL, Luria DM, et al: Impaired detection of ventricular tachyarrhythmias by a rate-smoothing algorithm in dual-chamber implantable defibrillators: intradevice interactions. J Cardiovasc Electrophysiol 13:312-318, 2002. 53. Cooper JM, Sauer WH, Verdino RJ: Absent ventricular tachycardia detection in a biventricular implantable cardioverterdefibrillator due to intradevice interaction with a rate-smoothing pacing algorithm. Heart Rhythm 1:728-731, 2004. 54. Shivkumar K, Feliciano Z, Boyle NG, Wiener I: Intradevice interaction in a dual chamber implantable cardioverter-defibrillator preventing ventricular tachyarrhythmia detection. J Cardiovasc Electrophysiol 11:1285-1288, 2000. 55. Gunderson BD, Gillberg JM, Wood MA, et al: Development and testing of an algorithm to detect implantable cardioverterdefibrillator lead failure. Heart Rhythm 3:155-162, 2006. 56. Zhang X, Volosin K, Kumar A, et al: Withholding ICD shocks for detected lead fractures. Heart Rhythm 6:S249, 2009. 57. Ellenbogen KA, Wood MA, Kapadia K, et al: Short-term reproducibility over time of right ventricular pulse pressure as a potential hemodynamic sensor for ventricular tachyarrhythmias. Pacing Clin Electrophysiol 15:971-974, 1992. 58. Leitch J, Klein G, Yee R, et al: Feasibility of an implantable arrhythmia monitor. Pacing Clin Electrophysiol 15:2232-2235, 1992. 59. Swerdlow CD: Implantation of cardioverter-defibrillators without induction of ventricular fibrillation. Circulation 103:2159-2164, 2001. 60. Michaud J, Horduna I, Dubuc M, Khairy P: ICD-unresponsive ventricular arrhythmias. Heart Rhythm 6:1827-1829, 2009. 61. Ruetz L, Koehler JL, Jackson TE, Belk P: Sinus rhythm R-wave amplitude does not predict undersensing of ventricular fibrillation by implantable cardioverter-defibrillators. Circ Arrhythm Electrophysiol 120:S650, 2009. 62. Tung L, Tovar O, Neunlist M, et al: Effects of strong electrical shock on cardiac muscle tissue. Ann NY Acad Sci 720:160-175, 1994. 63. Winkle RA, Bach SM, Jr, Echt DS, et al: The automatic implantable defibrillator: local ventricular bipolar sensing to detect ventricular tachycardia and fibrillation. Am J Cardiol 52:265-270, 1983. 64. Goldberger JJ, Horvath G, Donovan D, et al: Detection of ventricular fibrillation by transvenous defibrillating leads: integrated versus dedicated bipolar sensing. J Cardiovasc Electrophysiol 9:677-688, 1998. 65. Yee R, Jones DL, Jarvis E, et al: Changes in pacing threshold and R wave amplitude after transvenous catheter countershock. J Am Coll Cardiol 4:543-549, 1984. 66. Jung W, Manz M, Moosdorf R, et al: Changes in the amplitude of endocardial electrograms following defibrillator discharge: comparison of two lead systems. Pacing Clin Electrophysiol 18:2163-2172, 1995. 67. Kuhlkamp V, Dornberger V, Mewis C, et al: Clinical experience with the new detection algorithms for atrial fibrillation of a defibrillator with dual chamber sensing and pacing. J Cardiovasc Electrophysiol 10:905-915, 1999. 68. Wilkoff BL, Kuhlkamp V, Volosin K, et al: Critical analysis of dual-chamber implantable cardioverter-defibrillator arrhythmia detection: results and technical considerations. Circulation 103:381-386, 2001. 69. Swerdlow CD: Supraventricular tachycardia–ventricular tachycardia discrimination algorithms in implantable cardioverterdefibrillators: state-of-the-art review. J Cardiovasc Electrophysiol 12:606-612, 2001. 70. Gunderson B, Patel A, Bounds C: Automatic identification of implantable cardioverter-defibrillator lead problems using intracardiac electrograms. Comput Cardiol 29:121-124, 2002. 71. Swerdlow C, Shivkumar K: Implantable cardioverterdefibrillators: clinical aspects. In Zipes DP, Jalife J, editors: Cardiac electrophysiology: from cell to bedside, ed 4, Philadephia, 2004, Saunders, pp 980-993. 72. Pinski SL: 2:1 tracking of sinus rhythm in a patient with a dualchamber implantable cardioverter-defibrillator: what is the mechanism? J Cardiovasc Electrophysiol 12:503-504, 2001. 73. Hsu SS, Mohib S, Schroeder A, Deger FT: T-wave oversensing in implantable cardioverter-defibrillators. J Interv Card Electrophysiol 11:67-72, 2004. 74. Cao J, Shrivastav M, Koehler J, et al: Automatic identification of T-wave oversensing by patterns of alternating amplitude and frequency content in implantable cardioverter defibrillator electrograms [abstract]. Heart Rhythm 5:S094, 2008.

75. Garcia-Moran E, Mont L, Brugada J: Inappropriate tachycardia detection by a biventricular implantable cardioverterdefibrillator. Pacing Clin Electrophysiol 25:123-124, 2002. 76. Gunderson B, Swerdlow C, Wilcox J, et al: Causes of ventricular oversensing in implantable cardioverter-defibrillators: implications for diagnosis of lead fracture. Heart Rhythm 7:626-633, 2010. 77. Lloyd M, Hayes D, Friedman P: Troubleshooting. In Cardiac pacing and defibrillation: a clinical approach, Armonk, NY, 2000, Futura, pp 347-452. 78. Swerdlow CD, Gunderson BD, Ousdigian KT, et al: Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads. Circulation 118:2122-2129, 2008. 79. Cheung JW, Iwai S, Lerman BB, Mittal S: Shock-induced ventricular oversensing due to seal plug damage: a potential mechanism of inappropriate device therapies in implantable cardioverter-defibrillators. Heart Rhythm 2:1371-1375, 2005. 80. Kallinen LM, Hauser RG, Lee KW, et al: Failure of impedance monitoring to prevent adverse clinical events caused by fracture of a recalled high-voltage implantable cardioverter-defibrillator lead. Heart Rhythm 5:775-779, 2008. 81. Chung EH, Casavant D, John RM: Analysis of pacing/ defibrillator lead failure using device diagnostics and pacing maneuvers. Pacing Clin Electrophysiol 32:547-549, 2009. 82. Hauser RG, Hayes DL: Increasing hazard of Sprint Fidelis implantable cardioverter-defibrillator lead failure. Heart Rhythm 6:605-610, 2009. 83. Pinski S, Eguia L, Sgarbossa E, Trohman R: Incidence and causes of commited shocks in noncommited implantable defibrillators [abstract]. J Am Coll Cardiol 39:93A, 2002. 84. Sweesy MW, Holland JL, Smith KW: Electromagnetic interference in cardiac rhythm management devices. AACN Clin Issues 15:391-403, 2004. 85. Lau CP, Leung SK, Tse HF, Barold SS: Automatic mode switching of implantable pacemakers. II. Clinical performance of current algorithms and their programming. Pacing Clin Electrophysiol 25:1094-1113, 2002. 86. Israel CW: Analysis of mode switching algorithms in dual chamber pacemakers. Pacing Clin Electrophysiol 25:380-393, 2002. 87. Lam CT, Lau CP, Leung SK, et al: Improved efficacy of mode switching during atrial fibrillation using automatic atrial sensitivity adjustment. Pacing Clin Electrophysiol 22:17-25, 1999. 88. Leung SK, Lau CP, Lam C, et al: Programmed atrial sensitivity: a critical determinant in atrial fibrillation detection and optimal automatic mode switching [in process citation]. Pacing Clin Electrophysiol 21:2214-2219, 1998. 89. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 107:2932-2937, 2003. 90. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial [see comment]. JAMA 288:3115-3123, 2002. 91. Melzer C, Sowelam S, Sheldon TJ, et al: Reduction of right ventricular pacing in patients with sinus node dysfunction using an enhanced search AV algorithm. Pacing Clin Electrophysiol 28:521-527, 2005. 92. Sweeney M, Nsah E, McGrew F, et al: Reduction in ventricular pacing and its long-term clinical outcomes: preliminary results of the Save Pace Trial [abstract]. Heart Rhythm 2:S322, 2005. 93. Olshansky B, Day J, McGuire M, Pratt T: Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV): design and clinical protocol. Pacing Clin Electrophysiol 28:62-66, 2005. 94. Deering T, Wilensky M, Tondato F, et al: Auto intrinsic conduction search algorithm: a prospective analysis [abstract]. Pacing Clin Electrophysiol 26:1080, 2003. 95. Savoure A, Frohlig G, Galley D, et al: A new dual-chamber pacing mode to minimize ventricular pacing. Pacing Clin Electrophysiol 28:S43-S46, 2005. 96. Sweeney MO, Shea JB, Fox V, et al: Randomized pilot study of a new atrial-based minimal ventricular pacing mode in dualchamber implantable cardioverter-defibrillators. Heart Rhythm 1:160-167, 2004. 97. Pascale P, Pruvot E, Graf D: Pacemaker syndrome during managed ventricular pacing mode: what is the mechanism? J Cardiovasc Electrophysiol 20:574-576, 2009. 98. Mansour F, Talajic M, Thibault B, Khairy P: Pacemaker troubleshooting: when MVP is not the most valuable parameter. Heart Rhythm 3:612-614, 2006. 99. Gillis AM, Purerfellner H, Israel CW, et al: Reducing unnecessary right ventricular pacing with the managed ventricular pacing mode in patients with sinus node disease and AV block. Pacing Clin Electrophysiol 29:697-705, 2006. 100. De Voogt WG, Vonk BF, Albers BA, Hintringer F: Understanding capture detection. Europace 6:561-569, 2004. 101. Schuchert A, Frese J, Stammwitz E, et al: Low settings of the ventricular pacing output in patients dependent on a pacemaker: are they really safe? Am Heart J 143:1009-1011, 2002. 102. Splett V, Trusty JM, Hayes DL, Friedman PA: Determination of pacing capture in implantable defibrillators: benefit of evoked response detection using RV coil-to-can vector. Pacing Clin Electrophysiol 23:1645-1650, 2000.



103. Crossley GH, Mead H, Kleckner K, et al: Automated left ventricular capture management. Pacing Clin Electrophysiol 30:1190-1200, 2007. 104. Sperzel J, Binner L, Boriani G, et al: Evaluation of the atrial evoked response for capture detection with high-polarization leads. Pacing Clin Electrophysiol 28:S57-S62, 2005. 105. Sperzel J, Milasinovic G, Smith TW, et al: Automatic measurement of atrial pacing thresholds in dual-chamber pacemakers: clinical experience with atrial capture management. Heart Rhythm 2:1203-1210, 2005. 106. Olson W: Safety margins for sensing and detection: programming tradeoffs. In Kroll M, Lehmann M, editors: Implantable cardioverter-defibrillator therapy: the engineering-clinical interface, Norwell, Mass, 1996, Kluwer Academic Publishers, pp 389-420. 107. Anderson MH, Murgatroyd FD, Hnatkova K, et al: Performance of basic ventricular tachycardia detection algorithms in implantable cardioverter-defibrillators: implications for device programming. 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Wietholt D, Kuehlkamp V, Meisel E, et al: Prevention of sustained ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators: the PREVENT study. J Interv Card Electrophysiol 9:383-389, 2003. 161. Pollak WM, Simmons JD, Interian A, Jr, et al: Pacemaker diagnostics: a critical appraisal of current technology. Pacing Clin Electrophysiol 26:76-98, 2003. 162. Hammel E, Bertrand B, et al: Appropriate detection of guidant pacemaker stored electrograms assessed by centralized arrhythmia workstation [abstract]. Pacing Clin Electrophsyiol 23:680, 2000. 163. Passman RS, Weinberg KM, Freher M, et al: Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias. J Cardiovasc Electrophysiol 15:773-777, 2004. 164. Seidl K, Rameken M, Breunung S, et al: Diagnostic assessment of recurrent unexplained syncope with a new subcutaneously implantable loop recorder. REVEAL Investigators. Europace 2:256-262, 2000. 165. Israel CW, Gascon D, Nowak B, et al: Diagnostic value of stored electrograms in single-lead VDD systems. Pacing Clin Electrophysiol 23:1801-1803, 2000. 166. Glotzer TV, Daoud EG, Wyse DG, et al: The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol 2:474-480, 2009. 167. Capucci A, Santini M, Padeletti L, et al: Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. J Am Coll Cardiol 46:1913-1920, 2005. 168. Ricci RP, Morichelli L, Gargaro A, et al: Home monitoring in patients with implantable cardiac devices: is there a potential reduction of stroke risk? Results from a computer model tested through Monte Carlo simulations. J Cardiovasc Electrophysiol 20:1244-1251, 2009. 169. Ip J, Waldo AL, Lip GY, et al: Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: rationale, design, and clinical characteristics of the initially enrolled cohort. The IMPACT study. Am Heart J 158:364370, 2009. 170. Morris MM, KenKnight BH, Lang DJ: Detection of atrial arrhythmia for cardiac rhythm management by implantable devices. J Electrocardiol 33(Suppl):133-139, 2000. 171. Schuchert A, Boriani G, Wollmann C, et al: Implantable dualchamber defibrillator for the selective treatment of spontaneous atrial and ventricular arrhythmias: arrhythmia incidence and device performance. J Interv Card Electrophysiol 12:149-156, 2005. 172. Krahn AD, Klein GJ, Yee R, Norris C: Maturation of the sensed electrogram amplitude over time in a new subcutaneous implantable loop recorder. Pacing Clin Electrophysiol 20:16861690, 1997. 173. Thaker JP, Patel MB, Jongnarangsin K, et al: Electromagnetic interference in an implantable loop recorder caused by a portable digital media player. Pacing Clin Electrophysiol 31:13451347, 2008. 174. Trigano A, Blandeau O, Dale C, et al: Risk of cellular phone interference with an implantable loop recorder. Int J Cardiol 116:126-130, 2007. 175. Gimbel JR, Zarghami J, Machado C, Wilkoff BL: Safe scanning, but frequent artifacts mimicking bradycardia and tachycardia during magnetic resonance imaging (MRI) in patients with an

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implantable loop recorder (ILR). Ann Noninvas Electrocardiol 10:404-408, 2005. 176. Brignole M, Bellardine Black CL, Thomsen PE, et al: Improved arrhythmia detection in implantable loop recorders. J Cardiovasc Electrophysiol 19:928-934, 2008. 177. Sarkar S, Ritscher D, Mehra R: A detector for a chronic implantable atrial tachyarrhythmia monitor. Biomed Eng IEEE Trans 55:1219-1224, 2008. 178. Hindricks G, Pokushalov E, Urban L, et al: Performance of a new leadless implantable cardiac monitor in detecting and quantifying atrial fibrillation: results of the XPECT Trial. Circ Arrhythm Electrophysiol 3:141-147, 2010. 179. Bordachar P, Garrigue S, Reuter S, et al: Hemodynamic assessment of right, left, and biventricular pacing by peak endocardial acceleration and echocardiography in patients with

end-stage heart failure. Pacing Clin Electrophysiol 23:1726-1730, 2000. 180. Hegbom F, Hoff PI, Oie B, et al: RV function in stable and unstable VT: is there a need for hemodynamic monitoring in future defibrillators? Pacing Clin Electrophysiol 24:172-182, 2001. 181. Kaye G, Astridge P, Perrins J: Tachycardia recognition and diagnosis from changes in right atrial pressure waveform: a feasibility study. Pacing Clin Electrophysiol 14:1384-1392, 1991. 182. Sharma AD, Bennett TD, Erickson M, et al: Right ventricular pressure during ventricular arrhythmias in humans: potential implications for implantable antitachycardia devices. J Am Coll Cardiol 15:648-655, 1990. 183. Ellenbogen KA, Lu B, Kapadia K, et al: Usefulness of right ventricular pulse pressure as a potential sensor for hemo­

dynamically unstable ventricular tachycardia. Am J Cardiol 65:1105-1111, 1990. 184. Turcott R: Detection of hemodynamically unstable arrhythmias using subcutaneous photoplethysmography [abstract]. Heart Rhythm 2:S83, 2005. 185. Bourge RC, Abraham WT, Adamson PB, et al: Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol 51:1073-1079, 2008. 186. Kroll MW, Swerdlow CD: The future of the implantable defibrillator. In Efimov I, Kroll M, Tchou P, editors: Cardiac bioelectric therapy: mechanisms and practical implications, Berlin, 2008, Springer Verlag, pp 551-570.

4 

Engineering and Construction of Pacemaker and ICD Leads HARIS M. HAQQANI  |  LAURENCE M. EPSTEIN  |  JOSHUA M. COOPER*

Tremendous advances have occurred in implanted cardiac device

therapy, from the evolution of pacemakers to the modern era of highvoltage defibrillation and resynchronization devices. Advances in the components, integrated circuitry, size, and software of the implantable pulse generator are readily apparent, but the revolutionary progress in the design and manufacture of device leads is often not appreciated. In any device system, the lead is the critical interface linking the pulse generator and the myocardium; it allows for communication of electrical signals from the heart to the pulse generator through the sensing circuitry, and in the reverse direction, it allows for bradycardia pacing or tachyarrhythmia therapy. Although leadless pacing1 and defibrillation2 device systems are being actively developed, leads clearly will remain an integral component of device therapy for the foreseeable future. Whether used for pacing, resynchronization, or defibrillation, and regardless of their internal structural design, all leads contain several common components, including electrodes, conductors, insulators, fixation mechanisms, and connector pins. Defibrillation leads also contain shock coils for the delivery of high-voltage, high-current electrical discharges to terminate ventricular fibrillation. This chapter examines each of these elements as well as the overall design, construction, and evolution of pacemaker and implantable cardioverterdefibrillator (ICD) leads.

Pacing Leads HISTORICAL MILESTONES IN DEVELOPMENT Permanently implantable pacing leads evolved from the temporary pacing wires that were first used to provide bradycardia support.3 The initial permanent transvenous leads were unipolar and consisted of a basic conductor, an insulator, and a connector pin. The electrodes were large and polished with high-polarization properties, low electrodetissue impedance, and excessive current drain. No lumen was present in these leads to allow for stylet insertion, so lead implantation was a long, difficult task. Also, no fixation mechanism was present, so lead displacement rates were high. The development of bipolar pacing leads minimized far-field oversensing,4 requiring a major reconsideration of lead body design and structure, because two longitudinal conductors needed to coexist inside the lead, separated only by a thin layer of insulation. This and subsequent increases in complexity required advances in materials science so as not to compromise reliability. The development of passive-fixation tines was a huge step forward and dramatically reduced the rate of reoperation for lead dislodgement compared with existing flange-tipped pacing leads.5-7 Active-fixation helices were introduced subsequently and further improved the stability of implanted leads. Modern electrodes were developed with small geometric surface area but large effective area as a result of porous surfaces, and these optimized the trade-off between high current *Disclosures: Dr. Haqqani is the recipient of a Training Fellowship from the National Health and Medical Research Council of Australia (544309) and the Bayer Fellowship from the Royal Australasian College of Physicians. Drs. Cooper and Epstein have received modest honoraria from Boston Scientific, Medtronic, St. Jude Medical, Biotronik, and Spectranetics.

density and low polarization. Chronic threshold rises and late exit block were still major problems in cardiac pacing at that stage, however, and remained so until the revolutionary incorporation of an elutable dexamethasone reservoir into a porous-tip electrode, essentially eliminating this complication.8 Although this likely resulted from the glucocorticoid and not the redesigned porous titanium-tip electrode, this remained unproved until a pioneering randomized double-blind trial compared two otherwise identical leads and electrodes, with and without steroid elution.9 This unequivocally demonstrated the benefit was the result of the dexamethasone. Subsequent advances have included the universal standardization of connector pins (and consequently device headers), improving lead longevity through the use of better component materials, and improving sensing through the use of narrower bipoles. LEAD STRUCTURE AND POLARITY The basic functions of any cardiac device lead—pacing and sensing— require conductors for current flow between the pulse generator and myocardium and insulators to prevent short-circuiting of this current. These elements may be configured in two ways. First, a pace/sense circuit may be composed of a lead containing one conductor that connects to a negatively charged tip electrode, the cathode, from which electrons flow through the myocardium and thoracic cavity back to the active, positively charged pulse generator (IPG), the anode (Fig. 4-1, A). Such a lead, with only one conductor and electrode, is called a unipolar lead because only one electrode is in contact with the heart (although it is part of a bipolar circuit). It has been established that pacing thresholds are lower at most pulse widths when the intracardiac pacing electrode is configured as the cathode rather than as the anode10 (see Chapter 1). Although once the only option, unipolar leads have largely been replaced by bipolar leads. The alternative system consists of a lead body containing two conductors (separated and surrounded by insulation) that connect to a cathode-tip electrode and an anode ring electrode located several millimeters more proximally (Fig. 4-1, B). The IPG is not an active electrode in a bipolar circuit, and such leads are said to have bipolar configuration. Unipolar systems have a large interelectrode distance from the tip of the intracardiac lead to the IPG, and this large field of view makes them vulnerable to the oversensing of myocardial signals (T waves or electrograms from another chamber, known as “crosstalk”) and farfield nonmyocardial signals such as pacing artifacts (another form of crosstalk), skeletal myopotentials, and nonphysiologic electrical “noise” in up to 38% of patients.11 Electrical signal oversensing can have significant consequences on pacing behavior, including ventricular output inhibition and inappropriate mode switching caused by far-field ventricular oversensing on the atrial channel.12,13 Because of the additional consequence of inappropriate shock delivery if oversensing were to occur in an ICD, it is particularly important for ICD leads to have bipolar sensing circuitry. Since the IPG itself serves as one of the electrodes in a unipolar system, skeletal muscle capture and pectoral muscle stimulation may result in the setting of a higher programmed pacing output. Bipolar leads have been shown to have similar but slightly higher, acute and chronic stimulation thresholds to unipolar leads.4 Bipolar leads also carry an element of redundancy in that they

127

128

SECTION 1  Basic Principles of Device Therapy

Unipolar

Bipolar

+

RV lead

RV lead +

–

A

–

B

Figure 4-1  A, Unipolar pacing circuit, with an intracardiac cathode located on the lead tip in the right ventricle (RV). The circuit is completed by the active pulse generator, which forms the anode. B, In a bipolar circuit, both cathode and anode are located on the lead, with the anode generally formed by a ring electrode proximal to the tip cathode.

can be used in either the bipolar or the unipolar configuration, as in isolated failure of the proximal, anodal conductor, with no demonstrated difference in performance between the two pacing configurations.14 In addition, the much lower amplitude of the bipolar pacing artifact greatly reduces the likelihood of crosstalk and oversensing. The great advantage of bipolar leads is related to their superior sensing properties. These factors have led to the near-universal adoption of the bipolar lead as the configuration of choice in cardiac device systems.15 The only potential disadvantage of bipolar leads is that reliability is lower than with the less complicated unipolar lead,16 although some studies have not supported this contention.15,17 However, insulation failure usually has negligible effects on unipolar lead performance, a clear reliability advantage. In terms of the structure of the lead body, the simple, single-conductor design of unipolar leads had to be modified to accommodate the greater number of components and increased complexity of the bipolar lead body. There are two main bipolar lead designs, coaxial and coradial (Fig 4-2). Coaxial leads have an inner conductor that extends down the length of the lead to the tip electrode, the cathode, arranged in a coil configuration with a central lumen to allow for passage of a stylet at implantation. This coil is covered by a cylindrical length of inner insulation, which in turn

is wrapped by another coil conductor that also runs down the lead to the ring electrode, the anode. A second, outer layer of insulation and lead covering protect the ring conductor from the outside environment, thereby completing the design. Although this coaxial model has been the industry standard for pacing leads for many years, the resulting bulk and stiffness of this four-layer design are significant compared with the simpler unipolar leads. Coradial bipolar leads addressed some of these concerns with new conductor and insulator technology that was subsequently used in ICD lead design. In coradial leads, a single coil extends down the length of the lead (again with a central lumen to allow for stylet insertion) and consists of two parallel, alternating conductor strands, one of which connects to the cathode and the other to the anode. Each conductor strand is individually coated with a bonded layer of ethylene tetrafluoroethylene (ETFE) fluoropolymer insulation (originally by DuPont, Wilmington, Del), which serves to insulate each strand from the other, despite being intertwined. The single, two-component coil is surrounded by a single, outer insulation covering.18 These leads have comparable bulk (~5F diameter) and flexibility to unipolar leads, often with tines or a fixed, nonretractable helix to minimize size; electrical parameters and reliability have not been demonstrably inferior to coaxial leads.18-21 Defibrillator leads have even greater complexity, with two, three, or four conductors that connect to the pacing/sensing electrodes as well as to the high-voltage shocking coil(s), depending on the specific type of lead. Because of the prohibitive bulk that would result from a coaxial design with more than two conductors, ICD leads generally have a different type of structure, known as a multilumen design. This type of ICD lead consists of a long cylinder of insulating material, with separate internal channels running down its length (Fig. 4-3). Each conductor runs down an individual channel, usually with its own additional covering tube of insulation. The configuration and number of channels differ, depending on the number of conductors, the specific manufacturer, and whether air-filled channels are also

Urethane ETFE

Sense

COAXIAL DESIGN Ring Tip

A

Outer insulation Inner insulation

CORADIAL DESIGN

Compression lumen

Defib

Tip

PTFE

B

Ring

Outer insulation

Figure 4-2  A, Coaxial lead body design consists of two nested coil conductors to the tip and ring electrodes, each wrapped in a separate layer of insulation. The inner coil connects to the tip cathode and contains a central lumen for stylet passage; the outer coil connects to the ring anode. B, In coradial design, a single coil contains the parallel conductor strands to the tip and ring electrodes, with each strand covered by a fluoropolymer insulator. A surrounding layer of outer insulation covers the lead body.

HP silicone

Pace

Figure 4-3  Multilumen ICD lead design consists of a single body of insulation with several internal channels that contain the conductor elements (central pace/sense coil and outer high-voltage cables), each covered by its own layer of fluoropolymer insulation. A surrounding layer of outer polyurethane-based insulation is present. HP, Highperformance. (Courtesy Medtronic, Minneapolis.)



4  Engineering and Construction of Pacemaker and ICD Leads

Deflectable delivery catheter

129

DFT conductor strands are then formed into multifilar (i.e., multiple strands or filaments) coils with a central lumen in coaxial leads, as described earlier, or further coated in a layer of ETFE fluoropolymer before being arranged in bifilar coradial coils,28 again with a central lumen. The alternative way of forming a composite-wire conductor is the drawn brazed strand (DBS) method, generally consisting of six strands of a high-resistance material (e.g., MP-35N) that are tightly molded over a central strand of silver, such that the inner, low-resistance metal is forced between and around the strong outer strands (Fig. 4-5, Drawn filled tube

Figure 4-4  Isodiametric, lumenless, 4.1F pacing lead (Model 3830 SelectSecure). There is no central lumen for stylet passage, so the lead is deployed through an 8.5F steerable catheter delivery system (SelectSite C304) at implantation. (Courtesy Medtronic, Minneapolis.)

incorporated into the design to improve lead handling and protect the conductors from flexion-related damage in the dynamic intracardiac and intravascular environment. One other lead body structure worth mentioning are small (4.1F diameter), isodiametric, lumenless pacing leads (Model 3830 SelectSecure; Fig. 4-4). The lack of a central lumen and the use of a conductor cable (rather than coil) allows for increased insulation redundancy, high tensile strength, and reduced bulk. It also means that the activefixation helix is nonextendable because there is no central coil conductor to transmit torque from the connector pin to extend or retract the helix. Fixation of such leads to the myocardium is achieved by turning the entire lead body. To enable implantation without a stylet, the lead is deployed through an 8.5F steerable catheter delivery system (SelectSite C304). Short-term results from this lead have been reasonable, with no signs of increased lead displacement or fracture risk.22,23 The small external diameter of this lead has been considered to be of some benefit in pediatric patients24 and patients with congenital heart disease,25 but the suggestion of a resulting improvement in chronic venous patency from the smaller size is yet to be substantiated in longterm follow-up. In addition, selective site pacing, in both the atria and the ventricles, is facilitated by the deflectable sheath, although steerable and preformed stylets can also be used with conventional leads to achieve this. No published experience with extraction of chronically placed lumenless leads exists, and the lack of a lumen to accommodate a lead-locking device may be a significant disadvantage of this design.

Silver core

MP−35N

A Drawn brazed strand

CONDUCTORS Both the coaxial and the coradial bipolar pacing lead body designs have been in widespread use and proved to be relatively fracture resistant over time. This durability is at least partially related to the materials and design of the conductor elements used in pacing leads. One study found conductor fracture over a 17-year follow-up in 19 of 561 right ventricular pacing leads (3.4%) and then generally at points of high stress, such as at the lead anchoring sleeve and the costoclavicular ligament (subclavian crush).26 The basic material used for most conductors over the last 3 to 4 decades has been MP-35N (SPS Technologies, Cleveland), an alloy of nickel, cobalt, chromium, and molybdenum. The main advantage of MP-35N is its high strength and resistance to corrosion.27 Its main disadvantage is its high electrical resistance, but this has been overcome with the development of composite-wire conductors that incorporate low-resistance metals such as silver and stainless steel with high-strength materials such as titanium, platinum, and platinum-iridium alloy. In pacing leads, these materials are generally incorporated into a drawn filled tube (DFT) composite-wire conductor strand consisting of a thick, strong body of MP-35N or titanium that has been filled with a central core of softer, low-resistance metal such as silver, often encased in a further outer shell of platinum alloy (Fig. 4-5, A). The

Silver

MP−35N

B Figure 4-5  Composite-wire conductor design. A, Drawn filled tube (DFT) composite wire; thick body of MP-35N is filled with softer, lowresistance silver. B, Drawn brazed strand (DBS) wire; six strands of MP-35N are tightly molded over a central strand of silver. DFT and DBS composite wire can then be further fashioned into multifilar coil and cables. (Courtesy St Jude Medical, Sylmar, Calif.)

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SECTION 1  Basic Principles of Device Therapy

B). This results in a low-resistance, durable composite conductor wire that can once again be formed into a multifilar coil for use in pacing leads.29 However, it is also used to form strong, multifilar, braided cables that are employed as the conductors for the high-voltage circuitry of ICD leads. DBS cables are discussed later.

Environmental stresss cracking

INSULATION Pacing lead insulation is a critical and vulnerable component that is often the cause of lead failure.30,31 One of the problems with the major materials used for lead insulation (polyurethane, silicone rubber, fluoropolymers) is that they were not originally designed specifically for this purpose, and each has disadvantages when used as part of a biologic pacing system. They were incorporated by early lead engineers into their designs for lack of any purpose-built alternatives, and it is only recently that any viable, tailored alternatives have been developed. Poly(ether)urethane is a synthetic, segmented polymer with very high tensile strength and resistance to mechanical abrasion. From a physical perspective, this means that a thinner layer of insulation can be used to cover the lead conductors, thereby reducing the overall lead diameter. Also, polyurethane has excellent lubricity and handling characteristics, with a low frictional coefficient, which can facilitate implantation of two or three lead systems by decreasing the physical interactions between the leads. However, polyurethane leads are stiffer and not fully biostable, being subject to in vivo polymer degradation that can cause insulation and late lead failure.32 The two main types of polyurethane are Pellethane 80A and Pellethane 55D (Upjohn, CPR Division, Torrance, Calif), with 80A particularly prone to biodegradation. Two mechanisms of in vivo, biologically mediated degradation of polyurethane predominate: environmental stress cracking (ESC) and metal ion oxidation (MIO)33 (Fig. 4-6). When polyurethane is subjected to repeated mechanical stresses in the presence of surface-active agents provided by macrophages and α2-macroglobulin, parallel polymer molecules are disordered and interchain bonds weakened. This is the mechanism of ESC,34 manifesting as a deep surface cracking visible with electron microscopy, particularly at the anchoring sleeve and venous entry portions of the lead. By comparison, no mechanical stress is required for MIO to develop because this is a chemical reaction that occurs particularly at the conductor-insulator interface.35 Biologic oxidants, such as peroxide from surrounding inflammatory cells,36 can result in the release of metal cations from the conductor, especially cobalt and nickel ions. These cations cause oxidation of the soft zones in the polymer, starting at the α-carbon of the ether bond and resulting in chain break. The harder Pellethane 55D is much less susceptible to both ESC and MIO than 80A but is significantly stiffer. Nevertheless, the long-term performance of Pellethane 55D has been much better than Pellethane 80A, a material notoriously prone to failure. Silicone rubber (polysiloxane) has none of the disadvantages of polyurethane. It is completely inert and biostable over extended periods and thus not vulnerable to MIO or ESC. Silicone is more flexible, which may decrease the risk of damage to cardiac structures, including lead perforation. It is also more thermally resistant to the effects of electrocautery, which can be a significant advantage during pulse generator replacement or system revision.37 Initially, a softer peroxide-catalyzed silicone rubber, MDX4-4515-50A, was used for pacing leads, but new versions with higher tensile strength and abrasion resistance have been developed. These include high-performance (HP) silicone, extra-tear-resistant (ETR) silicone, and Novus (Med4719, Nusil Technologies, Carpinteria, Calif), produced by hybridizing HP and MDX4 silicone. Unfortunately, no variety of silicone rubber has the positive characteristics of polyurethane, including surface lubriciousness and ease of handling. Although these friction-related problems of silicone can be addressed by an outer layering of polyurethane, the main problem with silicone relates to its lower tensile strength and susceptibility to abrasion and tears (Fig. 4-7, A). This means that silicone insulation is more prone to damage during

A Metal ion oxidation

B Figure 4-6  Mechanisms of polyurethane insulation failure on electron microscopy. A, Environmental stress cracking (ESC) results from mechanical stress, leading to disruption of polymer molecule arrays and interchain bonds. B, Metal ion oxidation (MIO) of the polymer soft segments causes polymer chain break. (Courtesy St Jude Medical, Sylmar, Calif.)

implantation and subsequent interactions in the device pocket, and that a thicker insulation layer must be used to maintain lead reliability, thereby increasing lead bulk. Also, as with glass, silicone is a fluid material and thus prone to a gradual flowing process away from pressure points, known as “cold flow,” which can lead to thinned, denuded, and abraded troughs or depressions adjacent to areas of thickened rubber polymer32 (Fig. 4-7, B). The fluoropolymers polytetrafluoroethylene (PTFE) and ETFE (DuPont) have some of the advantages of both silicone and polyurethane, with good abrasion resistance and biostability.38 Unfortunately, their great stiffness excludes them from functioning as the primary insulating material in any lead, but they can be used, as outlined earlier, as a thin coat on conductor strands, particularly in coradial leads. This inner insulating layer can prevent electrical communication between conductor strands and can also protect them from interacting with an adjacent outer layer of polyurethane, thereby reducing MIO. Recently, the development of a specific insulation material for cardiac leads has suggested that the deficiencies of the standard insulators in pacing leads may finally be addressed. The material is a copolymer hybrid composed of 48% silicone, 40% polyurethane hard segment, and 12% polyhexamethylene oxide soft segment; it is called Elast-Eon (Aortech Biomaterials, Clayton, Victoria, Australia). This



4  Engineering and Construction of Pacemaker and ICD Leads

Abrasion: 4 years

A

Silicone abrasion

Cold flow: 1 year

B

Silicone cold flow

Figure 4-7  Mechanisms of silicone rubber insulation failure. A, Weaker molecular structure of silicone makes it more prone to abrasions and tears at points of higher mechanical stress. B, Glasslike fluid composition of silicone renders it susceptible to cold flow away from areas of higher pressure. (Courtesy St Jude Medical, Sylmar, Calif.)

blending of insulating materials results in the product having the strength, lubricity and abrasion resistance of polyurethane, but the flexibility and biostability of silicone.39 Early bench and clinical testing have been promising to date, with little evidence of cold flow, ESC, or MIO phenomena, the main weaknesses of silicone and polyurethane. The material has been used in the St. Jude Medical Optim family of pacing (Models 1888T and 2088T) and ICD leads (Durata), but no long-term data on its chronic performance are yet available.

131

although vitreous carbon cathodes have particular strength, inertness, and long-term electrical reliability.45 More important than the precise material composition of electrodes seems to be their geometry, particularly the surface area. A large cathodal surface area in contact with the endocardium results in a low current density at the electrode-tissue interface and consequently a higher capture threshold. As tip electrodes were reduced in surface area, apart from better thresholds, higher tissue-electrode impedances were also seen, and this increased pulse generator longevity.46,47 Against this beneficial effect of a smaller electrode is the adverse effect on tissue polarization seen with a smaller electrode surface area. Polarization refers to the electrical afterpotential generated at the electrode-tissue interface by ionic movement induced by the pacing stimulus. At pacing pulse delivery, a layer of positively charged cations is attracted to and surrounds the negatively charged cathode (and a larger layer of negatively charged anions surrounds the cation layer), which opposes current flow from the pacing electrode. This polarization potential is recorded as an afterpotential following the stimulus artifact. To maximize the advantages of small-radius electrodes, yet minimize the disadvantage of the polarization effect more prominent with smaller electrode surface area, current electrodes are small in size but have a complex, porous microscopic surface (Fig. 4-8). Regardless of the method of achieving a complex, highly textured surface, such as coating the electrode with microspheres or a woven mesh of microscopic metallic fibers, the resulting large surface area has proved beneficial with regard to pacing and sensing performance. Titanium nitride–coated or iridium-coated cathodes with fractal surface structure achieve the goal of enhanced surface area with a negligible polarization signal48 (Fig. 4-9). Such electrodes have permitted the development of beat-by-beat automatic capture threshold and pacing output management systems that measure the evoked myocardial response following every pacing stimulus. By verifying myocardial capture for each paced beat, with the immediate delivery of a backup higher-output pulse if capture is lost (Fig. 4-10), the pacemaker can maintain a pacing output only marginally above the capture threshold, thereby prolonging pulse generator battery life.49 Another type of automatic threshold algorithm does not verify beat-to-beat capture, but performs an automatic threshold test daily and adjusts the pacing output accordingly (with larger safety margin above capture

ELECTRODES Electrodes represent the final common electrical and mechanical interface between the lead and myocardium. The design and construction of the electrodes influence the acute and chronic electrical performance of the lead. Because the electrode type also determines the fixation mechanisms employed and the lead tip pressure generated, however, mechanical problems such as lead dislodgement and cardiac perforation can also be affected by the tip electrode. The materials used for lead electrodes have evolved over the past 40 years and have included titanium, anodized platinum, platinumiridium alloys, Elgiloy (an alloy of cobalt, iron, chromium, molybdenum, nickel, and manganese), and vitreous carbon. All these display relative inertness in vivo, which minimizes inflammatory reactions and corrosion over the long term. Minor corrosion is seen, however, with Elgiloy and platinum alloys when in situ for extended periods, although this is of uncertain clinical significance.40 While attempting to control for other differences, several human and animal studies have compared these materials, but the results are conflicting.41-44 In general, applications have been found for these materials in electrode composition, with most having reasonable in vivo performance and longevity,

Figure 4-8  Sintered porous electrode (left) and laser porous electrode (right). (From Hirshorn MS, Holley LK, Skalsky M, et al: Characteristics of advanced porous and textured surface pacemaker electrodes. PACE 6:525-536, 1983.)

132

SECTION 1  Basic Principles of Device Therapy

A

B

Figure 4-9  Magnified view (A) and electron micrograph (B) of fractally coated, titanium nitride electrode tip, which optimizes surface area and minimizes polarization resistance. (Courtesy St Jude Medical, Sylmar, Calif.)

threshold). These types of automatic capture-detection algorithms can be unreliable in the setting of a significant polarization afterpotential, because a large polarization signal cannot be distinguished from the local myocardial evoked response.50 Electrodes implanted in myocardium elicit a strong foreign body granulomatous reaction that results in the formation of a local fibrous A

B

capsule at the lead tip, which can have a profound effect on electrical performance. Smooth-surfaced electrodes elicit the formation of a thick, electrically insulating capsule of fibrous and granulation tissue that may impede electrode fixation to the endocardium.51 Complex, porous electrodes, in contrast, are manufactured to have extremely small (20-50 µ in diameter) surface pores that allow for endocardial C

D

II

V5

B 2 1

3

Figure 4-10  Automatic loss of capture algorithm (Autocapture). The atrioventricular (AV) delay is shortened to ensure ventricular pacing (A). The pacing output is automatically decreased until loss of capture is detected by failure to sense a myocardial-evoked response at B2. A backup 5-V pulse is delivered at B3, followed by an automatic gradual increase in pacing output that restores myocardial capture (C), and then resumption of dual-chamber pacing is seen, with the programmed AV delay (D). Modern leads produce negligible polarization afterpotential and thus allow for high-fidelity sensing of the myocardial-evoked response. (Courtesy St Jude Medical, Sylmar, Calif.)



4  Engineering and Construction of Pacemaker and ICD Leads

Steroid plug

133

1699T Optisense, St. Jude Medical) with a standard 10-mm spacing, the close-spaced bipole showed minimal far-field ventricular sensing at a sensitivity of 0.3 mV, compared to 30% 1-year incidence in the standard-bipole group.56 This translated into a large reduction in inappropriate mode switch events, from 23% in the control group to 4% in the narrow-bipole group. FIXATION MECHANISMS

A

Steroid plug

B Figure 4-11  Dexamethasone-eluting reservoirs in passive-fixation (A) and active-fixation (B) leads. (Courtesy St Jude Medical, Sylmar, Calif.)

attachment by way of tissue ingrowth into these regions, which yields a mechanical advantage in addition to the electrical benefits mentioned earlier. A fibrous reaction also occurs with highly textured electrodes, but a lesser insulating effect is observed because the electrically active myocardium is closer to the electrode,51 resulting in improved electrical parameters over time.52 To curtail further the fibrous reaction elicited by the electrode and to decrease the incidence and magnitude of chronic threshold rises, a pharmacologic anti-inflammatory strategy was pursued with glucocorticoid-eluting porous electrodes (Fig. 4-11). These leads showed excellent long-term capture and sensing parameters, with a dramatic reduction in late exit block (i.e., loss of myocardial capture).8 In an elegant and seminal double-blind randomized trial, Mond et al.9 conclusively proved the beneficial effect of steroid elution by comparing two otherwise identical porous titanium electrodes, only one of which incorporated dexamethasone in its tip. There was no difference in capture threshold seen at implant. Although there was an expected late rise in threshold in the standard leads starting at 2 weeks, this was completely abolished in the steroid-eluting lead, both during the trial period and in long-term follow-up.53 Animal studies confirmed that the biologic basis of this electrophysiologic effect was through the glucocorticoid-induced attenuation of the inflammatory reaction, with thinner, less cellular fibrous capsules.54 In bipolar leads, another factor affecting electrical performance, particularly far-field sensing, is the interelectrode distance between the tip cathode and the ring anode. Narrow-spaced bipolar electrodes in atrial leads have been shown to reduce far-field ventricular electrogram sensing without compromising atrial sensing.55 In a randomized trial that compared an atrial lead with a 1.1-mm tip-to-ring spacing (Model

Initial pacemaker leads had no fixation mechanisms, so lead dislodgement rates were high. The first solutions to this problem were wedgeshaped flanges and fins, but these had limitations. The development of scalloped tines was the first robust solution to the problem of lead displacement,5 and comparisons with earlier methods of passive fixation were favorable.57 Tines are usually constructed from the same material as the covering insulation of the lead, typically silicone rubber, and protrude backward from the base of the tip electrode. Their orientation is designed to allow advancement of the lead for initial implantation but to prevent retraction and dislodgement by engaging the myocardial trabeculae of the right atrial appendage and right ventricular apex (Fig. 4-12, A). Although passive-fixation tined leads perform well, with low rates of dislodgement, they are less reliable for pacing at nontraditional sites, and the development of active-fixation leads with a helix at the tip improved the options for pacing site selection (Fig. 4-12, B). These leads generally have an extendable-retractable screw made of platinumiridium or similar alloy that is usually electrically active as part of the cathode. This terminal helix is deployed (i.e., extended out of lead) with clockwise rotation of the connector pin, which transmits torque via the central coil conductor to the helix mechanism at the other end of the lead. A small number of leads use a stylet-driven extension-retraction mechanism. Some smaller-diameter leads have a fixed helix that requires rotation of the entire lead body around the stylet for deployment into the myocardium. Steroid elution from a reservoir at the base of the helix helps to dampen the inflammatory reaction produced by traumatic engagement of the myocardium by the screw. Active- and passive-fixation leads perform similarly overall,58 with some differences related to their construction. Active leads tend to be easier to extract, whereas passive leads tend to have lower chronic thresholds with higher impedances that prolong pulse generator longevity. The clinician must always consider the potential for perforation59 and trauma to surrounding structures60 when using active-fixation leads.61

A

Passive fixation

B

Active fixation

Figure 4-12  Lead fixation mechanisms. A, Passive-fixation tined lead. The tines are constructed of outer insulation material and facilitate advancement of the lead but prevent its retraction by engaging myocardial trabeculae in the right ventricle or right atrial appendage.  B, Extendable-retractable helix is deployed to screw directly into the myocardium in an active-fixation lead. (Courtesy St Jude Medical, Sylmar, Calif.)

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SECTION 1  Basic Principles of Device Therapy

Figure 4-13  Lead anchoring sleeves. Each sleeve contains up to three grooves to allow for suturing the sleeve to the lead body, then to the underlying deep fascia in the pocket. (Courtesy St Jude Medical, Sylmar, Calif.)

IS-1 (pace/sense)

A

LEAD ANCHORING SLEEVES Securing the lead body to the fascia or muscle at the floor of the device pocket at implantation is an important step to prevent lead dislodgement. The sutures used must be fastened firmly but, given the relative fragility of lead insulation as previously outlined, must not be allowed to compromise the lead structure or integrity (Fig. 4-13). Although the anchoring sleeve provides a mechanism to achieve this balance, there has been little development in this area. After being tied down tightly, sleeves made of MDX silicone were found to produce much lower lead deformation than ETR silicone,62 but no long-term in vivo data are available. Suture sleeves that grasp the lead by snapping into place (rather than relying on circumferential deformation of sleeve by encircling suture) have been proposed but are not in current use. CONNECTOR TERMINAL PINS The connector terminal pin forms the interface of the lead with the header of the pulse generator and has gone through significant evolution. With successive generations of pulse generator and lead technology, various standards for connector terminal pins for pacing leads have been used,63,64 as well as two different pin-fixation mechanisms within the device header, the side lock, and the now-universal set screw. Reliability has been high with both pin-header fixation interfaces, although the more forgiving tolerance of the set-screw platform has led to its widespread adoption.65 This design requires a self-sealing grommet to cover the head of the set screw and prevent corrosion of the pin or header connections because pocket fluid enters the header. Sealing fins are required around the lead body or within the header channel to prevent fluid leaking into the header at that site, regardless of the fixation mechanism. Different patterns of connector pins include the 5- and 6-mm-long pins, the 3.2-mm low-profile pin, the VS-1 pin, and the current standard IS-1 connector pin (Fig. 4-14). Compatibility CONNECTOR SIZE OR STANDARD

6 mm, 5/6 mm, 5 mm

3.2 mm

IS−1 Figure 4-14  Evolution of pace/sense connector pins, culminating in current IS-1 standard (bottom).

• 3.2 mm diameter • no sealing rings in header • short receptacle for B lead terminal

IS-1

Figure 4-15  A, IS-1 pace/sense connector pin terminal. B, Cross section of IS-1 header.

between terminal pin type and header channel type is still of major concern when changing pulse generators in patients with older leads. Modern pulse generator headers conform to IS-1 specifications (Fig. 4-15) and are backwards-compatible with VS-1 pins. Occasionally, for example, adapters may be required to downsize a long pin connector to an IS-1 header.

  Resynchronization Leads The symptomatic and prognostic benefits of cardiac resynchronization therapy (CRT) in congestive heart failure patients with electrical dyssynchrony (asynchrony), usually in the form of native left bundle branch block (LBBB) or right ventricular pacing, have been repeatedly demonstrated in those already receiving maximal medical therapy.66,67 Leads used for providing CRT are exposed to different implant conditions than conventional pacing leads and thus have different design parameters. The benefits of CRT were first demonstrated with the placement of left ventricular (LV) epicardial leads. CRT leads can be implanted directly on the epicardium by an open or video-assisted thoracotomy. These leads are, or have similar characteristics to, standard epicardial pacing leads (Fig. 4-16). They are generally sutured or screwed in place on the lateral LV wall. Increasingly, patients who undergo cardiac surgery for coronary disease or valve dysfunction, but who also have heart failure, LV dysfunction, or a chronic need for pacing because of heart block, are having LV epicardial leads implanted at surgery, with the terminal pin end tunneled up to the left infraclavicular fossa for future connection to a CRT device. However, a transvenous approach to LV epicardial lead placement avoids the morbidity and mortality of an open surgical approach and is usually the preferred initial implantation method for patients not otherwise scheduled for cardiac surgery. Therefore, most candidates for CRT therapy have their LV lead implanted transvenously into one of the venous tributaries of the coronary sinus. Compared with standard endocardial pacing, this technique has two challenges:(1) placing the lead into a desirable location despite venous tortuosities, acutely angled branch ostia, obstructive venous valves, patches of myocardial scar with high capture threshold, and regions of phrenic nerve capture, and (2) once placed, achieving stable lead fixation within the thinwalled coronary vein (vs. relative ease of standard tined electrode or active-fixation helix obtaining purchase on endocardial wall of cardiac chamber).



4  Engineering and Construction of Pacemaker and ICD Leads

Figure 4-16  Epicardial active-fixation steroid-eluting leads, implanted surgically. Lead on the left has an active-fixation helix, whereas two electrodes on the right are sutured to the epicardium. (Courtesy St Jude Medical, Sylmar, Calif.)

LEAD PLACEMENT AND FIXATION MECHANISMS For accessing the stimulation site, CRT lead systems come with a range of outer guide introducers to facilitate coronary sinus cannulation and provide support during lead placement. Although the initial transvenous CRT leads were stylet driven, over-the-wire leads were rapidly introduced because of difficulty negotiating venous tortuosities and acute takeoff angles. The development of an over-the-wire system was a major advance,68 and such leads are routinely required to select and place leads in the best possible target venous branches, usually over the posterolateral left ventricle. These leads allow for front or back loading of a 0.014-inch angioplasty wire into the stylet lumen. With or without the assistance of inner guiding catheters, the wire may be used to subselect target venous branches (including those with acute takeoff angles) and the lead may then be tracked over the pre-positioned wire. Obtaining distal vascular access with a wire also allows for venoplasty to facilitate lead placement in the setting of stenotic vascular segments.

135

Once at the target site, and with retraction of the wire or stylet back into the lead body, most lead tips have some degree of memory and assume the form of a preshaped curvature, which may be a smooth curve, an angled cant, or a spiral (Fig. 4-17). These distal lead shapes provide some degree of stability in the target vein by exerting modest lateral pressure on the inner vein surface, thereby increasing friction and a resistance to forward or backward migration. LV lead models that have no distal curvature use small, distal tines to engage the venous wall, but these tines likely have a reduced ability to fix the lead passively in place, particularly in larger vein branches. Thus, stability of tined leads probably relies more on lead flexibility and the cumulative friction along the lead length wherever it is in contact with the venous wall. These straight leads seem to have a higher risk of dislodgement, and subsequent generations of CRT leads have not incorporated tines. In most cases the major contributor to LV lead fixation in the coronary venous system has been the extent to which the outer lead diameter is circumferentially opposed to the inside wall of a venous tributary of given caliber. If the lead has been advanced snugly into a vein branch, significant fixation friction forces may be generated, but lead stability remains variable. The risk of dislodgement also depends on upstream factors, including the number and size of redundant loops and tortuosities in the proximal course of the lead body, cardiac motion, tricuspid valve regurgitation, and interactions with other intracardiac hardware, which can each generate traction forces on the LV lead. Consequently, there is a significant rate of CRT lead displacement of up to 1% to 5% that may require surgical lead revision if there is a significant change in electrode position, ventricular capture threshold, or phrenic capture.66,69,70 The concept of active-fixation leads in the coronary venous system has been brought to clinical practice with the Attain StarFix lead (Model 4195, Medtronic, Minneapolis), which has three sets of deployable lobes that fold out and protrude from the lead body just proximal to the tip (Fig. 4-18). These 12 circumferential lobes are extended by an external sliding-push tubing mechanism, and radiopaque markers are used to indicate whether one, two, or all three sets of lobes are extended or retracted. In a recent multicenter study of 408 implants, Crossley et al.71 found a very low lead dislodgment rate of 0.7% with stable electrical parameters over a mean follow-up of 23 months. Phrenic nerve capture with this unipolar lead required lead revision in 11 patients (2.5%). This reasonable performance must be weighed, however, against potential difficulties of extraction, which fortunately has not been a major issue in the other LV lead models to date. In this study of the active-fixation LV lead, 26 patients (6.4%) underwent an

Figure 4-17  Representative variety of currently available resynchronization leads with differing passive-fixation curvatures. (Courtesy Medtronic, Minneapolis; St Jude Medical, Sylmar, Calif; and Boston Scientific, St Paul, Minn.)

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SECTION 1  Basic Principles of Device Therapy

output is inadvertently programmed below the true LV capture threshold, because RV anodal capture is mistaken for LV cathodal capture during threshold testing.75 No significant differences have been noted in the short-term and long-term complication rates after CRT implantation among the various leads and CRT systems commercially available.76

ICD Leads

Figure 4-18  Active-fixation resynchronization lead (Attain StarFix, Model 4195) with deployable lobes to grip the lumen of the coronary venous tributary in which it is implanted. (Courtesy Medtronic, Minneapolis.)

attempt at lead revision. In two patients, no attempt to remove the lead was made, and in the remaining 24 revisions, five attempts failed (21%). These patients had maximum implant duration of only 941 days. Of the seven patients who had a lead in situ for more than 1 year, four (57%) were unable to be extracted. This study is similar to the experience of Nagele et al.,72 who encountered extraction difficulty caused by immobile lobes in two patients. The ability to un-deploy the lobes seems to be independent of the duration of implant and may be related to local branch vein thrombosis or an ingrowth of fibrous tissue through the lobe loops. Although both these studies were small and represented early experience with this lead, the difficulties with extraction of the StarFix lead contrast with the relative ease of extraction of chronic LV leads, even after extended periods since implantation.73 DESIGN OF CRT LEADS The original CRT leads were exclusively unipolar because of size considerations, given that LV leads had to be advanced through a long, smaller-caliber sheath that was used to engage the coronary sinus selectively. An early example was the EasyTrak lead family (Models 4510/11/12/13, Guidant, St. Paul, Minn.), which had a 6F lead body diameter and an LV-1 connector terminal pin compatible only with LV-1 headers on Guidant CRT pulse generators. Since then, numerous developments in lead size, polarity, and CRT device programmability have greatly increased the options available to the implanting operator, including lead and device options to manage the problem of phrenic nerve capture, as well as to find suitable pacing configurations in the setting of myocardial scar. Most significantly, bipolar CRT leads were developed that were no larger in diameter than the previous generation of unipolar leads and that could therefore be deployed through the same sheath delivery systems and into venous branches of the same caliber. Newer LV lead versions include 4F to 5F leads that can be advanced through smaller venous subselection sheaths, into more diminutive vein branches, which increases the number of lead positioning options. The interelectrode distance in bipolar CRT leads varies from 8 to 21 mm. The great advantage of bipolar leads is the option of programming between multiple different pacing electrode permutations, including true bipolar and extended bipolar configurations, with the option of selecting whether to use the LV tip or the LV ring electrode as the pacing cathode (Fig. 4-19). These programming options may be invaluable in the patient with posterolateral LV fibrosis or a large field of phrenic nerve capture, where an alternate pacing polarity may obviate the need for lead revision. True bipolar LV pacing also eliminates the problem of simultaneous right ventricular (RV) anodal capture, which can be seen in the setting of unipolar LV lead use and can sometimes partially undermine the benefit of LV pacing.74 Anodal capture from the RV ring or coil electrode can hinder proper CRT delivery by eliminating the ability to stimulate the left before the right ventricle, and occasionally by leading to absent LV pacing if the pacing

The development of the implantable cardioverter-defibrillator was a revolutionary step in the history of medicine.77 Sudden-death prevention became an achievable goal, initially in those who had survived cardiac arrest or malignant ventricular arrhythmias,78 but then in patients at risk of dying suddenly (primary prevention).79,80 Modern ICD systems are extremely sophisticated devices, frequently combined with CRT capability, that feature advanced rhythm-discrimination software, antitachycardia pacing (ATP) during capacitor charging, and high-voltage biphasic shocks, all in a pectorally implanted device of 40 cc or less. Advances in pulse generator technology and reliability are important but of limited relevance if progress cannot be matched in ICD lead design, development, and particularly durability. The reductionist view of ICD leads as simply being “pacemaker leads with additional shock coils” ignores the exponential rise in complexity as more components are added. This complexity puts pressure on long-term reliability in a device expected to cope repeatedly with 800-V highcurrent discharges and move with the heartbeat 37 million times annually. As longer follow-up data are published on both older and newer ICD leads, despite the innovations and developments in recent years, clearly this most vulnerable part of the ICD system continues to be prone to late failure.81-84 HISTORICAL EVOLUTION OF ICD LEADS Epicardial patches placed through thoracotomy were the leads first used in human ICD systems.77 The pulse generators in these systems were large and required placement in an abdominal pocket. Shock energy was delivered through a free-floating 12F nonpacing endovascular titanium spring coil that served as the anode, with the patch as the cathode. Sensing was accomplished initially by epicardial patches (or apical cup electrode in the first implant), but this sensing mechanism proved to be unreliable, and dedicated epicardial and endocardial leads were adopted early. These first-generation ICD systems had a high risk of complications, particularly in the large endovascular coil,

6

4

2

5

1 LV lead

RV lead

3

Figure 4-19  Multiple different pacing polarity configurations are possible with modern bipolar resynchronization leads and generators. Each arrow originates at the cathode and ends at the anode of current left ventricular (LV) lead pacing configurations. RV, Right ventricular.



4  Engineering and Construction of Pacemaker and ICD Leads

including superior vena cava thrombosis, coil fracture, insulation failure, and coil retraction into the subclavian vein caused by lack of a lead anchoring sleeve. Consequently, the second-generation ICD devices in the late 1980s were fully epicardial systems, with shock delivery between two epicardial patches and tachyarrhythmia sensing through an epicardial lead. Epicardial patches also had problems, however, including an ongoing infection and pericarditis risk,85 a possible adverse effect on transthoracic external defibrillation threshold, and a perioperative mortality of up to 4% at implantation in these patients, who were generally at high risk for thoracotomy or median sternotomy.86,87 These patch electrodes also displayed poor in vivo durability over time, with a failure rate of up to 28% at 4 years. More than half of patients with obvious lead failure or fracture were asymptomatic. The epicardial pace/sense leads incorporated in these systems were also suspect, with a failure rate of 14.1% at 8.5 years in one study, with lead fracture accounting for half these failures.88 In contrast to patch failure, patients with epicardial pace/sense lead failure were likely to develop multiple inappropriate ICD shocks from oversensing.89 By the early 1990s, advances in pulse generator design and technology allowed miniaturization for infraclavicular pectoral implantation, although this would require an entirely endocardial defibrillation, sensing, and pacing lead system. The initial transvenous leads were implanted with the pulse generator in an abdominal pocket, and the leads were tunneled subcutaneously from their pectoral vascular insertion site down to the abdomen. Such leads, including the Transvene family (Medtronic), were initially based on coaxial pacing lead platforms. Their development added ATP capability to ICD systems, but also new lead-related problems. Apart from the large bulk of these leads (up to 12F), predisposing to venous occlusion and subclavian crush,90 lead failure was frequent, demonstrating a progressive late incidence related to both conductor fracture and insulation defects.91 Addressing these problems required paradigm shifts in lead body design as well as advancements in materials technology, which ushered in the modern era of multilumen, narrow-caliber transvenous ICD leads. ICD LEAD STRUCTURE The basic elements in pacing leads are also found in transvenous ICD leads: conductors, insulation, electrodes, fixation mechanisms, and connector terminals. In addition, however, ICD leads contain the highvoltage circuitry that links the pulse generator with one or two highvoltage shock coils located on the lead body (Fig. 4-20). One of these coils is located in the right ventricle, a variable distance proximal to the tip pace/sense electrode, whereas the other coil, if present, is positioned on the part of the lead located in the superior vena cava.

A

137

Two basic lead body architectures can be used to incorporate all these elements into an ICD lead. First, the coaxial structure, a design essentially borrowed from the pacing platform of the same name, consists of concentric coiled conductors (to tip electrode, ring electrode, and shock coils) layered inside one another and separated by intervening layers of insulation, with the whole assembly housed in an outer covering layer of insulation. The innermost coil connected down to the tip conductor contained a lumen for stylet insertion that assisted with endocardial lead implantation. The best known examples of this design were the Medtronic Transvene and the Ventritex TVL families of ICD leads, first used in the early 1990s. Although initial reports were positive,92 subsequent longitudinal data showed that these leads were prone to early and late failure, caused by a combination of conductor and insulation problems.83,91 Whether these failures were mainly related to the limited durability of the conductor and insulation (polyurethane 80A) materials, or resulted from an inherent weakness of the bulky coaxial architecture in situations of increased complexity as found in ICD leads, will never be known; this design was no longer in use by the late 1990s. The second main paradigm for ICD lead structure, and still the dominant architecture for modern ICD leads, is the multilumen design, in which parallel cable and coil conductors run to the tip, with ring and shock electrodes in separate channel lumens, all within a single frame of insulation; some models also have additional, empty decompression lumens. The conductor to the tip electrode is conventionally coiled and contains the central lumen for stylet insertion. The coil also permits the transfer of torque when the implanting physician rotates the pace/sense connector terminal pin to deploy an active-fixation helix at the distal lead tip. Each conductor, both cable and coil, is invested with an inner layer of insulation, typically of fluoropolymer type, and the entire lead body is encased in a further outer insulation layer (see Fig. 4-3). ICD LEAD SENSING DESIGN Sensing function is critical in ICD systems to allow for accurate rhythm discrimination and to prevent inappropriate shocks from oversensing as well as failure of tachyarrhythmia treatment caused by undersensing. Therefore, unipolar ICD leads were not developed because of the prohibitive risk of oversensing noncardiac potentials, such as pectoral and diaphragmatic myopotentials. Bipolar ICD lead sensing can be arranged according to one of two paradigms: integrated bipolar and dedicated bipolar (also called true bipolar) designs. Sensing in integrated bipolar leads occurs between the tip electrode and the RV shock coil, which doubles as the sensing anode, the distal extent of which is located 6 to 15 mm proximal to the tip. By comparison, dedicated bipolar leads additionally include a conventional ring electrode (the

B

Figure 4-20  A, Dual-coil ICD lead with second high-voltage shock coil residing in the superior vena cava. B, Single-coil ICD lead with one shock coil in the right ventricle only. The active ICD pulse generator generally serves as the cathode or anode for the first phase of biphasic shocks.

138

SECTION 1  Basic Principles of Device Therapy

Integrated bipole lead

12 mm RV high-voltage electrode

A Dedicated bipole lead RV high-voltage electrode

B

25 mm

Ring for pacing and sensing

Figure 4-21  Design pullback. “Pullback” refers to the distance between the lower active edge of the right ventricular (RV) defibrillation electrode and the RV apex. Design pullback should be minimized for lower defibrillation thresholds. The diagrams show the impact of sensing methods on catheter design and the magnitude of the RV electrode pullback. A, Leads using integrated bipolar sensing/pacing methods (from tip to RV defibrillation electrode) typically have a shorter pullback distance (e.g., 12 mm here). B, Leads using dedicated bipolar sensing/ pacing methods have larger distances from catheter tip to active RV defibrillation electrode because of sensing ring (e.g., 25 mm here).

anode) 10 to 15 mm back from the tip, similar to a bipolar pacing lead (Fig. 4-21). The additional electrode means that an extra conductor is required in dedicated bipolar leads, but the smaller anode in these leads confers superior sensing performance with reduced far-field oversensing.93,94 The larger sensing anode (the distal shock coil) in integrated bipolar leads may be of particular concern in patients with small right ventricles, where the proximal end of the coil may extend across the tricuspid anulus and thereby pose a risk of far-field atrial oversensing.93 Integrated bipolar leads may be more prone to oversensing highfrequency respirophasic noise transients (i.e., diaphragmatic myopotentials), which may cause pacing inhibition and inappropriate shocks.95 The increased current density at the smaller anode of a dedicated bipolar lead does, however, increase the likelihood of anodal myocardial stimulation in CRT systems in which LV pacing is programmed in an “extended bipolar” fashion, with the RV ring doubling as the LV pacing anode,75 although in the current era of bipolar LV leads and pacing vector programmability, this is less of a concern. The main theoretical advantage of integrated bipolar leads, apart from their greater simplicity (which may reduce the chance for component failure), relates to the smaller distance between the RV shock coil in these leads and the RV apex, because there is no intervening ring electrode between the shock coil and the lead tip. This is known as the pullback distance, and data suggest a modestly improved defibrillation threshold with shorter pullback distance,96,97 although this was more important before the current era of high-output, biphasic devices and greater defibrillation safety margins. Theoretical concerns about differences in R-wave amplitudes between the two lead designs have not been borne out by comparative studies,98 but some studies suggest longer sensing latency98 with integrated bipolar leads, as well as the potential for undersensing of postshock ventricular fibrillation, presumably from local myocardial stunning around the shock coil and its proximity to the tip cathode.99,100 This phenomenon was not seen when the shock coil was more than 6 mm from the tip electrode. However, in terms of sensing de novo ventricular fibrillation, no significant differences have been demonstrated between the two lead platforms,101 and both are in clinical use today, although dedicated bipolar systems are implanted more frequently. CONDUCTORS As with pacing leads, similar materials are used in ICD lead conductor construction, with MP-35N being the dominant metal alloy employed. As outlined earlier, its advantages include its corrosion and fracture

resistance, but MP-35N–based conductors can still fracture at points of high stress (e.g., costoclavicular ligament). Recent testing suggests that this risk may be related to the presence of contaminant titanium inclusions, although this is controversial.102 In ICD systems, however, low-resistance conductors are essential to minimize voltage drops across the lead during high-voltage shock delivery. This requirement mandates the use of composite wire technology in which individual conductor strands combine higher-resistance MP-35N with a lowresistance metal such as silver in one of two patterns. The DFT pattern (see Fig. 4-5, A) produces conductor strands that are generally formed into coils, whereas in the DBS pattern (see Fig. 4-5, B), strands are twisted into multifilar braided cables (Fig. 4-22). The latter are particularly important in ICD leads because they have very high tensile strength and are more fracture resistant than coils. Failed ICD leads frequently demonstrate intact high-voltage cables with fractured pace/sense coil conductors. One conductor coil strand is generally required, as outlined earlier, to create a lumen for stylet insertion and to permit active-fixation helix deployment. However, the use of multiple parallel cables in a multilumen ICD lead design produces a stronger lead of smaller diameter than would be possible if only coiled conductors were used (as in the now-obsolete coaxial configurations). Each cable generally is housed in its own lumen of the multilumen lead by coating it with stiff, fluoropolymer insulation, preventing abrasion and damage to the soft, silicone-based insulation of the lead body (see Fig. 4-3). Decompression spaces, either within the lumen that houses a conductor or as separate channels in the housing insulation, may reduce the stress on the conductors, particularly in the setting of repeated lead flexion. ELECTRODES AND HIGH-VOLTAGE COILS Electrode composition and design in ICD leads conform to the same basic principles as outlined earlier for pacing leads, with steroid elution, current density, and polarization considerations again dictating the material composition of the tip cathode and ring anode in dedicated bipolar leads. Fixation mechanisms are also similar, with either electrically active extendable-retractable helices or flexible tines being employed. The high-voltage defibrillation shock coil is the defining feature of the ICD lead. All models include at least one shock coil, wrapped around the distal lead body, 5 to 6 cm in length and positioned in the right ventricle, whereas dual-coil leads have a second shock coil located either 17 cm or 21 cm proximal to the shaft end of the RV coil, with this superior vena cava (SVC) coil being slightly longer, 7 to 8 cm (see Fig. 4-20). The RV coil serves as the defibrillation anode or cathode during phase 1 of a biphasic shock, depending on how the ICD is programmed to deliver high-voltage therapy, with the SVC coil and active pulse generator casing together serving as the other shock cathode or anode. With single-coil ICD leads, the pulse generator solely functions as the second high-voltage electrode. Dual-coil leads may assist in lowering the defibrillation threshold (DFT), although the improvement in DFT with the addition of an SVC coil may be modest

Cable

ICD lead Coil Figure 4-22  Filar composition of unraveled high-voltage conductor cable alongside multifilar central pace/sense conductor coil in dissected ICD lead.



4  Engineering and Construction of Pacemaker and ICD Leads

and of greater benefit when the electrical impedance during single-coil shock delivery is higher.103 Because the high-voltage shock vector plays a role in DFT, some ICDs permit programming changes to eliminate either the SVC coil or the pulse generator itself from the shocking circuit, thereby improving the DFT in certain patients. Shocking coil– only leads are also available for implantation in the coronary sinus or azygous vein, or subcutaneously around the left thorax to improve the shock vector in patients with an elevated DFT and unreliable defibrillation with standard shock configurations. The materials used in shock coil construction are generally platinumiridium alloy or platinum alloy–clad tantalum, because titanium coils produce metallic oxides during high-voltage shocks that prevent their use in ICD leads. Polarization also affects the design of shock electrodes, as it does for pacing electrodes, but unlike the situation described earlier with pacing leads, fractally coating the shock coils does not improve defibrillation efficacy.104 However, some data suggest that iridium oxide coating may improve lead porosity and reduce polarization, even to the point of seeing a clinically meaningful reduction in DFT.105,106 Although an essential part of the ICD lead, the presence of endovascular defibrillation coils poses distinct physical problems, especially related to fibrous tissue ingrowth, which can make lead extraction difficult and potentially hazardous, as discussed later. INSULATION Essentially the same materials used in the manufacture of pacing lead insulation are also used in the context of ICD leads, and their respective advantages and disadvantages are discussed earlier. The multilumen design of ICD leads relies on a single, large-caliber body of insulation that contains the conductor lumens. Other insulation elements may include the jackets investing the conductor cables or an additional outer insulation covering, but the mechanical characteristics of the lead will largely be determined by the material used to construct the lead body. Because ICD leads are larger and more complex than pacemaker leads, silicone rubber is the dominant option for ICD lead body insulation; polyurethane 55D and fluoropolymers are too stiff for this purpose, and polyurethane 80A is too susceptible to biodegradation. The relative structural advantages of polyurethane 55D, lubriciousness and high tear strength, can be used to good advantage instead as an outer insulation layer surrounding the lead body. In this location it is far away from the metal conductors within the thick silicone rubber casing and a fluoropolymer jacket. This barrier prevents exposure to metal ions from the MP-35N conductor that can trigger the oxidative degradation of the soft, polyurethane segment. Likewise, although the major structural weaknesses of fluoropolymers (related especially to rigidity) preclude their use as the primary insulator, inner insulation of the coil and cable conductors is well suited to these highly biostable, abrasion-resistant materials. Generally, ETFE is used for coating of the cable conductors, and PTFE is used to line the central lumen lead body that houses the coil conductor. Although silicone rubber may be biostable and flexible enough to be used as the dominant material for ICD lead body insulation, its softness and high frictional coefficient make lead implantation difficult if the outermost surface of the ICD lead is silicone. Outer coverings of polyurethane may address this disadvantage to some extent, but the longterm mechanical risks related to silicone’s softness remain, as well as its susceptibility to abrasion and cold flow, and require the use of thicker silicone layers and thus increased lead caliber. This weakness is particularly marked at high-stress points such as at the costoclavicular ligament or in the pocket next to the pulse generator, where harsh local mechanical forces can lead to progressive insulation abrasion and local silicone thinning at pressure points. If lead insulation is sufficiently thinned or denuded that a low-impedance dielectric is created, particularly where a high-voltage conductor strand closely opposes the metal casing of the pulse generator in the device pocket, a short circuit with arcing can result during shock delivery, leading to ineffective defibrillation and permanent damage to the lead, the ICD circuitry, or both.107

139

As mentioned in the section on pacing leads, newer insulation materials are being developed for specific application in cardiac device leads, including one already in clinical use, Elast-Eon (Aortech Biomaterials, Clayton, Victoria, Australia). This substance is a hybrid copolymer composed of near-equal amounts of silicone and polyurethane and, in extensive laboratory experience, combines advantages of each.39 A family of pacing and ICD leads uses this material as an outer insulator (Optim, St. Jude Medical), but as yet no leads use this material for the primary lead body insulation. ICD LEAD CONNECTOR TERMINALS As with the initial CRT leads, early ICD leads had high-voltage circuitry that terminated proximally in connector pins compatible only with pulse generators made by the same vendor. This was a major problem, particularly at generator change procedures, when lack of hardware cross-compatibility could limit device selection options and increase procedural complexity. The first solutions involved developing a wide range of adapters and extenders that could be used to switch connector pin design. However, this added further complexity to the system, increased the number of electrical connection points, and introduced another component that was subject to similar modes of failure as the rest of the lead. Eventually, industry-wide standardization occurred in ICD systems, such that the pace/sense coil conductor terminates in a standard IS-1 pacing pin that is placed in the IS-1 port of the ICD header, and each high-voltage shock coil terminates in a standard DF-1 (ISO-11318) connector pin. In a dual-coil ICD lead, therefore, three tails ending in one IS-1 pin and two DF-1 pins emerge from a trifurcation yoke attached to the main lead body (Fig. 4-23). Three separate connector ports are found on the ICD header to accommodate the trifurcated end of a dual-coil ICD lead (one IS-1 port and two DF-1 ports). The yoke and lead tails of the ICD lead are subject to insulation and

A

IS−1

B

DF−1

Trifurcation yoke

C

Dual-coil ICD lead

Figure 4-23  ICD lead connector terminals. A, Standard IS-1 pace/ sense connector terminal. B, High-voltage DF-1 pin connects shock coil(s) to generator header. C, Proximal end of dual-coil ICD lead, with central IS-1 pace/sense pin, two high-voltage DF-1 pins, and trifurcation yoke to interface the three terminal pins with lead body.

140

SECTION 1  Basic Principles of Device Therapy

Pin geometry Low voltage

EXTRACTION CONSIDERATIONS

High voltage DF4−LLHH

Low

A

Low

High

Low = pacing/sensing

B

High High = cardioversion/defribrillation DF−4

Figure 4-24  Schematic representation and photograph of the IS-4/ DF-4 connector pin incorporating high-voltage and low-voltage elements in the one pin and thus obviating the need for an external trifurcation yoke. (Courtesy St Jude Medical, Sylmar, Calif.)

conductor failure, just as in the rest of the lead system. They also increase pocket bulk and may contribute to erosion risk, particularly in the setting of a dual-chamber or biventricular device system, with atrial and LV leads also present. Additional abandoned lead ends might also be present in the device pocket, if nonfunctional or redundant leads remain in place in the setting of lead failure or device upgrade. Besides increasing pocket bulk and interaction between device system components, the greater number of connector pins in a standard ICD lead allows inadvertent connector pin reversal in the device header, and the thick fibrous tissue that frequently encapsulates the lead trifurcation yoke can make a generator change or system revision more challenging. The development of the new IS-4/DF-4 standard connector pin has allowed the integration of two DF-1 high-voltage terminals and one bipolar IS-1 pace/sense terminal, all into one connector pin (Fig. 4-24). This new design addresses the mechanical issues associated with current multiterminal ICD leads, but the long-term reliability of these connector pins is currently unknown.108 In addition, this all-in-one connector pin design precludes the ability to replace a single component of the ICD lead, such as the pace/sense or a shocking coil component, in the setting of pace/sense malfunction or elevated DFT.

A

C

Increasingly, ICD systems are being implanted in younger patients with evolving indications outside the context of acquired cardiomyopathy. Channelopathies, arrhythmogenic RV dysplasia, congenital cardiac abnormalities, and sarcoidosis are indications for implant that affect younger patients, often children, who are expected to live with their ICD leads (since generators are changed at regular intervals) over their lifetime. Because ICD lead failure rates continue to accrue over time with current lead and materials technology,81 and lead infection can occur at any time without warning,109 lead manufacturers and physicians must give due consideration to this aspect of device therapy at implant. In addition, abandoned sterile leads are increasingly being removed to allow for reduced intravascular hardware burden, avoidance of inappropriate oversensing,110 and potentially increased longterm venous patency.111 Lead extraction, even with the modern tools and expertise,112 remains a potentially hazardous endeavor,113,114 particularly in young patients with long-standing dual-coil ICD leads, in which tissue ingrowth into the interstices between the helical turns of the shock coil wire may be causing dense, fibrous adhesions and tissue encapsulation of the lead body (Fig. 4-25). With some data indicating that defibrillation efficacy may not be significantly improved with the addition of the SVC coil,115 one approach is to consider implanting only single-coil ICD leads in patients expected to have longer implant duration.116 However, the real solution lies in the manufacture of shock coils that are easier to extract. All newer ICD lead bodies are isodiametric, with the same or a smaller maximal external diameter as proceeding from the proximal to the distal end of the lead (Fig. 4-26), and are 8-Fr size or smaller, which already improves the ease of extraction over previous transvenous ICD lead systems. Manufacturers also have taken different approaches to the problem of shock coil adhesion to the venous and cardiac walls102 (Fig. 4-27). Silicone backfilling of the interstices between the coils has been used in Medtronic leads to reduce fibrous tissue ingrowth. This approach may be effective117 but is limited by the

B

D

Figure 4-25  A, Chronically implanted ICD lead shows extensive adhesions binding the lead tip and shock coil to the trabeculated ventricular endocardium. B, After lead extraction, extent of shock coil–associated fibrosis is evident. C and D, Cross-sectional photomicrographs of a chronically implanted lead show fibrous tissue invasion into interstices between helical turns of the shock coil. (C and D courtesy St Jude Medical, Sylmar, Calif.)



4  Engineering and Construction of Pacemaker and ICD Leads

141

tissue ingrowth into, and local adherence of, the shocking coils over time. This has made ICD lead extraction easier in animal models, compared with an identical lead without covering sleeves.117 Recent clinical data have corroborated the potential benefit of modified ICD lead shock coils to improve the ease of extraction.119

Step up in diameter

ICD LEAD FAILURE

Figure 4-26  Lead body diameter may not be uniform throughout (top) or may be isodiametric (bottom), which improves the ability to extract chronically implanted leads. (Courtesy Medtronic, Minneapolis.)

surface area of the outer curvature of the round coil strands; the interstices cannot be fully obliterated because a large, exposed coil surface area is required for effective defibrillation. In Biotronik and St. Jude Medical leads, use of flatwire technology allows complete backfilling of the interhelix turns with silicone, allowing for a completely isodiametric shock coil segment while still reducing fibrous tissue ingrowth, as demonstrated in animal testing.102 A third strategy, employed in Boston Scientific leads, is to cover the defibrillation coils with a thin, encapsulating jacket of semiporous expanded polytetrafluoroethylene (ePTFE; Gore-Tex, Gore and Associates, Flagstaff, Ariz). As with all fluoropolymers, this material is abrasion and tear resistant as well as biostable, but it has been molecularly modified to make it semiporous. This allows for free fluid and ion flow so as not to significantly alter high-voltage electrical conductance during shocks from the underlying defibrillation coils. Consequently, no significant difference in clinical defibrillation efficacy has been demonstrated with the use of ePTFE coils.118 In the setting of an integrated bipolar sensing ICD lead and additional abandoned leads in the right ventricle, mechanical interactions between the large RV coil and adjacent lead materials may occasionally result in sensed electrical artifacts. Oversensing from this type of lead-on-lead interaction may be reduced or eliminated if the metal strands of the RV coil are covered by an ePTFE sleeve.110 The real advantage of the semiporous sleeve, however, is that cellular migration cannot occur into the covered underlying coil interstices, thus reducing Figure 4-27  Solutions to the problem of shock coil fibrous tissue ingrowth. Top panel shows the shock coil interstices backfilled with silicone. Middle two panels demonstrate effective backfilling between flatwire helix turns. Bottom two panels show an ePTFE covering sleeve over the shock coil. (Courtesy Medtronic, Minneapolis; St Jude Medical, Sylmar, Calif; and Boston Scientific, St Paul, Minn.)

The ICD lead is one of the most complex and vulnerable parts of the ICD system, and lead failure is a significant problem (Box 4-1). ICD lead failure, perhaps more so than with pacing lead failure, can lead to sudden death. This can occur not only by loss of pacing support in pacemaker-dependent patients, but as most often seen, also by causing recurrent inappropriate shocks due to oversensing of lead noise. These shocks can induce ventricular fibrillation, which the system may then not be able to defibrillate successfully.120 Early data from the transvenous lead experience held great promise,121 but late lead failure was seen at longer-term follow-up across all lead designs and manufacturers.81 Patient-related factors, such as excessive upper body activity, can contribute to ICD lead failure, as can procedural factors at implant, including subclavian (rather than cephalic) access,122,123 rough handling, traumatic transvenous insertion, overtorquing of active-fixation helices, and kinking of lead loops in the pocket. However, none of these factors is positively identified in most cases; the difficulty in extracting ICD leads (possibly with additional lead damage during its extraction) means that the failure mechanism usually remains obscure. A systematic solution to this problem must involve better ICD lead design and manufacture, with advances in materials technology. The Transvene family (Medtronic) of coaxial ICD leads had a structural failure rate of 38% at 8 years,83 which was more often caused by fracture of the outer high-voltage coil conductor than disruption of the polyurethane 80A insulation. Despite changes in design and materials, however, newer generations of ICD leads are also prone to late failure. Kleemann et al.81 found that cumulative survival of 990 ICD leads implanted between 1992 and 2005 was only 60% at 8 years, mainly from insulation defects, including in silicone-based leads. One in five leads implanted for a decade or longer failed. This study was weighted toward the older lead models, however, and 95% of implants were through subclavian access, which may have affected failure rates and mechanisms.

INGROWTH SOLUTIONS

Silicone backfill

Flatwire design and backfill

ePTFE covering sleeve

142

SECTION 1  Basic Principles of Device Therapy

Box 4-1 

SYMPTOMS AND SIGNS OF LEAD PROBLEMS Pacing/Sensing Oversensing (most common) caused by detection of noise Inappropriate shocks Inappropriate aborted shocks Inhibition of pacing Change in pacing impedance Prolonged oversensing immediately after shock delivery Undersensing in sinus rhythm Undersensing or nonsensing of VT/VF, with failure to deliver therapy Elevated pacing thresholds or noncapture Defibrillation Ineffective defibrillation Change in high-voltage impedance Sudden death VT/VF, Ventricular tachycardia/ventricular fibrillation.

In an industry-wide push for increasing miniaturization, smallcaliber ICD leads were introduced in the mid-2000s. Again, although early data gave no cause for alarm,124 more recently125 the small-caliber (6.6F) Sprint Fidelis lead (Models 6930/6931/6949/6948, Medtronic)

has been identified as much more prone than other contemporary lead models to early and late failure, usually presenting with conductor fracture, noise oversensing, and inappropriate shocks. Initial failure rate was 1.29% at 21 months,126 but risk appears to increase with time, up to 5.7% to 12.1% at 3 years,127-129 a failure rate of 3.75% per year, versus 0.58% per year or less for other contemporary ICD lead models.129,130 The mechanism in most cases is a fracture of the pace/ sense hexafilar cathode conductor, either proximally, near the lead anchoring sleeve, or distally, near the anode ring electrode.102,131 Although no longer being implanted, the problem of failure with this lead is ongoing because of the large number of patients with this model in place.

Conclusion The remarkable progress in lead technology over more than four decades has contributed greatly to the modern era of implantable cardiac rhythm devices. Advances such as fixation mechanisms, steroid elution, and transvenous defibrillation lead development have been milestone events, facilitated by ongoing improvements in materials science and lead design. However, the ideal of a small-caliber, easily implanted-extracted lead with reliable long-term performance does not yet exist. Future advances in lead engineering and construction that allow physicians to approach this goal are eagerly awaited.

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37. Lim KK, Reddy S, Desai S, et al: Effects of electrocautery on transvenous lead insulation materials. J Cardiovasc Electrophysiol 20:429-435, 2009. 38. De Voogt WG: Pacemaker leads: performance and progress. Am J Cardiol 83:187D-191D, 1999. 39. Jenney C, Tan J, Karicheria A, et al: A new insulation material for cardiac leads with potential for improved performance. Heart Rhythm 2:S318-S319, 2005. 40. Parsonnet V, Villanueva A, Driller J, Bernstein AD: Corrosion of pacemaker electrodes. Pacing Clin Electrophysiol 4:289-296, 1981. 41. Mugica J, Duconge B, Henry L, et al: Clinical experience with new leads. Pacing Clin Electrophysiol 11:1745-1752, 1988. 42. Molajo AO, Bowes RJ, Fananapazir L, et al: Comparison of vitreous carbon and Elgiloy transvenous ventricular pacing leads. Pacing Clin Electrophysiol 8:261-265, 1985. 43. Adler S, Spehr P, Allen J, Block W: Chronic animal testing of new cardiac pacing electrodes. Pacing Clin Electrophysiol 13:18961900, 1990. 44. Hirshorn MS, Holley LK, Hales JR, et al: Screening of solid and porous materials for pacemaker electrodes. Pacing Clin Electrophysiol 4:380-390, 1981. 45. Mugica J, Henry L, Attuel P, et al: Clinical experience with 910 carbon tip leads: comparison with polished platinum leads. Pacing Clin Electrophysiol 9:1230-1238, 1986. 46. Moracchini PV, Cornacchia D, Bernasconi M, et al: High impedance low energy pacing leads: Long-term results with a very small surface area steroid-eluting lead compared to three conventional electrodes. Pacing Clin Electrophysiol 22:326-334, 1999. 47. Berger T, Roithinger FX, Antretter H, et al: The influence of high versus normal impedance ventricular leads on pacemaker generator longevity. Pacing Clin Electrophysiol 26:2116-2120, 2003. 48. Bolz A, Hubmann M, Hardt R, et al: Low polarization pacing lead for detecting the ventricular-evoked response. Med Prog Technol 19:129-137, 1993. 49. Erdinler I, Akyol A, Okmen E, et al: Long-term follow-up of pacemakers with an autocapture pacing system. Jpn Heart J 43:631-641, 2002. 50. Luria D, Gurevitz O, Bar Lev D, et al: Use of automatic threshold tracking function with non-low polarization leads: risk for algorithm malfunction. Pacing Clin Electrophysiol 27:453-459, 2004. 51. MacGregor DC, Wilson GJ, Lixfeld W, et al: The porous-surfaced electrode: a new concept in pacemaker lead design. J Thorac Cardiovasc Surg 78:281-291, 1979. 52. Djordjevic M, Stojanov P, Velimirovic D, Kocovic D: Target lead– low threshold electrode. Pacing Clin Electrophysiol 9:1206-1210, 1986. 53. Mond HG, Stokes KB: The steroid-eluting electrode: a 10-year experience. Pacing Clin Electrophysiol 19:1016-1020, 1996. 54. Radovsky AS, Van Vleet JF: Effects of dexamethasone elution on tissue reaction around stimulating electrodes of endocardial pacing leads in dogs. Am Heart J 117:1288-1298, 1989. 55. De Groot JR, Schroeder-Tanka JM, Visser J, et al: Clinical results of far-field R-wave reduction with a short tip-ring electrode. Pacing Clin Electrophysiol 31:1554-1559, 2008. 56. Fung JW, Sperzel J, Yu CM, et al: Multicenter clinical experience with an atrial lead designed to minimize far-field R-wave sensing. Europace 11:618-624, 2009.



4  Engineering and Construction of Pacemaker and ICD Leads 57. Kertes P, Mond H, Sloman G, et al: Comparison of lead complications with polyurethane tined, silicone rubber tined, and wedge tip leads: clinical experience with 822 ventricular endocardial leads. Pacing Clin Electrophysiol 6:957-962, 1983. 58. Hidden-Lucet F, Halimi F, Gallais Y, et al: Low chronic pacing thresholds of steroid-eluting active-fixation ventricular pacemaker leads: a useful alternative to passive-fixation leads. Pacing Clin Electrophysiol 23:1798-1800, 2000. 59. Geyfman V, Storm RH, Lico SC, Oren JW: Cardiac tamponade as complication of active-fixation atrial lead perforations: proposed mechanism and management algorithm. Pacing Clin Electrophysiol 30:498-501, 2007. 60. Van Herendael H, Willems R: Contralateral pneumothorax after endocardial dual-chamber pacemaker implantation resulting from atrial lead perforation. Acta Cardiol 64:271-273, 2009. 61. Vlay SC: Complications of active-fixation electrodes. Pacing Clin Electrophysiol 25:1153-1154, 2002. 62. Li H, Helland J: In vitro evaluation of new design lead anchoring sleeves. Pacing Clin Electrophysiol 15:2005-2010, 1992. 63. Brown S: Connectors for implantable pacemaker leads. Pacing Clin Electrophysiol 3:620-621, 1980. 64. Doring J, Flink R: The impact of pending technologies on a universal connector standard. Pacing Clin Electrophysiol 9:11861190, 1986. 65. Tyers GF, Sanders R, Mills P, Clark J: Analysis of set screw and side-lock connector reliability. Pacing Clin Electrophysiol 15:2000-2004, 1992. 66. Cleland JG, Daubert JC, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539-1549, 2005. 67. Bristow MR, Saxon LA, Boehmer J, et al: Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004. 68. Purerfellner H, Nesser HJ, Winter S, et al: Transvenous left ventricular lead implantation with the Easytrak lead system: the European experience. Am J Cardiol 86:157K-164K, 2000. 69. Linde C, Abraham WT, Gold MR, et al: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol 52:1834-1843, 2008. 70. Beshai JF, Grimm RA, Nagueh SF, et al: Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 357:2461-2471, 2007. 71. Crossley GH, Exner D, Mead RH, et al: Chronic performance of an active-fixation coronary sinus lead. Heart Rhythm 7:472-478, 2010. 72. Nagele H, Azizi M, Hashagen S, et al: First experience with a new active fixation coronary sinus lead. Europace 9:437-441, 2007. 73. Hamid S, Arujuna A, Khan S, et al: Extraction of chronic pacemaker and defibrillator leads from the coronary sinus: laser infrequently used but required. Europace 11:213-215, 2009. 74. Freedman RA, Petrakian A, Boyce K, et al: Performance of dedicated versus integrated bipolar defibrillator leads with CRTdefibrillators: results from a prospective multicenter study. Pacing Clin Electrophysiol 32:157-165, 2009. 75. Thibault B, Roy D, Guerra PG, et al: Anodal right ventricular capture during left ventricular stimulation in CRT-implantable cardioverter defibrillators. Pacing Clin Electrophysiol 28:613-619, 2005. 76. Nof E, Gurevitz O, Carraso S, et al: Comparison of results with different left ventricular pacing leads. Europace 10:35-39, 2008. 77. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 303:322-324, 1980. 78. Connolly SJ, Hallstrom AP, Cappato R, et al: Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator Study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. Eur Heart J 21:20712078, 2000. 79. Moss AJ, Zareba W, Hall WJ, et al: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346:877-883, 2002. 80. Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352:225-237, 2005. 81. Kleemann T, Becker T, Doenges K, et al: Annual rate of transvenous defibrillation lead defects in implantable cardioverterdefibrillators over a period of >10 years. Circulation 115:2474-2480, 2007. 82. Ellenbogen KA, Wood MA, Shepard RK, et al: Detection and management of an implantable cardioverter defibrillator lead

failure: incidence and clinical implications. J Am Coll Cardiol 41:73-80, 2003. 83. Dorwarth U, Frey B, Dugas M, et al: Transvenous defibrillation leads: high incidence of failure during long-term follow-up. J Cardiovasc Electrophysiol 14:38-43, 2003. 84. Luria D, Glikson M, Brady PA, et al: Predictors and mode of detection of transvenous lead malfunction in implantable defibrillators. Am J Cardiol 87:901-904, 2001. 85. Chevalier P, Moncada E, Canu G, et al: Symptomatic pericardial disease associated with patch electrodes of the automatic implantable cardioverter defibrillator: an underestimated complication? Pacing Clin Electrophysiol 19:2150-2152, 1996. 86. Echt DS, Armstrong K, Schmidt P, et al: Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator. Circulation 71:289-296, 1985. 87. Gartman DM, Bardy GH, Allen MD, et al: Short-term morbidity and mortality of implantation of automatic implantable cardioverter-defibrillator. J Thorac Cardiovasc Surg 100:353-357, 1990. discussion 357-359. 88. Almassi GH, Olinger GN, Wetherbee JN, Fehl G: Long-term complications of implantable cardioverter defibrillator lead systems. Ann Thorac Surg 55:888-892, 1993. 89. Daoud EG, Kirsh MM, Bolling SF, et al: Incidence, presentation, diagnosis, and management of malfunctioning implantable cardioverter-defibrillator rate-sensing leads. Am Heart J 128:892-895, 1994. 90. Gallik DM, Ben-Zur UM, Gross JN, Furman S: Lead fracture in cephalic versus subclavian approach with transvenous implantable cardioverter defibrillator systems. Pacing Clin Electrophysiol 19:1089-1094, 1996. 91. Hauser RG, Cannom D, Hayes DL, et al: Long-term structural failure of coaxial polyurethane implantable cardioverter defibrillator leads. Pacing Clin Electrophysiol 25:879-882, 2002. 92. Golino A, Pappone C, Panza A, et al: Clinical experience with the transvenous Medtronic Pacer Cardioverter Defibrillator (PCD) system. Tex Heart Inst J 20:264-270, 1993. 93. Weretka S, Michaelsen J, Becker R, et al: Ventricular oversensing: A study of 101 patients implanted with dual chamber defibrillators and two different lead systems. Pacing Clin Electrophysiol 26:65-70, 2003. 94. Gradaus R, Breithardt G, Bocker D: ICD leads: design and chronic dysfunctions. Pacing Clin Electrophysiol 26:649-657, 2003. 95. Sweeney MO, Ellison KE, Shea JB, Newell JB: Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverter defibrillators. J Cardiovasc Electrophysiol 12:402-410, 2001. 96. Rashba EJ, Bonner M, Wilson J, et al: Distal right ventricular coil position reduces defibrillation thresholds. J Cardiovasc Electrophysiol 14:1036-1040, 2003. 97. Lang DJ, Heil JE, Hahn SJ, et al: Implantable cardioverter defibrillator lead technology: Improved performance and lower defibrillation thresholds. Pacing Clin Electrophysiol 18:548-559, 1995. 98. Frain BH, Ellison KE, Michaud GF, et al: True bipolar defibrillator leads have increased sensing latency and threshold compared with the integrated bipolar configuration. J Cardiovasc Electrophysiol 18:192-195, 2007. 99. Callans DJ, Swarna US, Schwartzman D, et al: Postshock sensing performance in transvenous defibrillation lead systems: analysis of detection and redetection of ventricular fibrillation. J Cardiovasc Electrophysiol 6:604-612, 1995. 100. Natale A, Sra J, Axtell K, et al: Undetected ventricular fibrillation in transvenous implantable cardioverter-defibrillators: prospective comparison of different lead system-device combinations. Circulation 93:91-98, 1996. 101. Goldberger JJ, Horvath G, Donovan D, et al: Detection of ventricular fibrillation by transvenous defibrillating leads: Integrated versus dedicated bipolar sensing. J Cardiovasc Electrophysiol 9:677-688, 1998. 102. Haqqani HM, Mond HG: The implantable cardioverterdefibrillator lead: principles, progress, and promises. Pacing Clin Electrophysiol 32:1336-1353, 2009. 103. Lubinski A, Lewicka-Nowak E, Zienciuk A, et al: Comparison of defibrillation efficacy using implantable cardioverterdefibrillator with single- or dual-coil defibrillation leads and active can. Kardiol Pol 63:234-241, 2005. discussion 242-243. 104. Gradaus R, Bocker D, Dorszewski A, et al: Fractally coated defibrillation electrodes: is an improvement in defibrillation threshold possible? Europace 2:154-159, 2000. 105. Niebauer MJ, Wilkoff B, Yamanouchi Y, et al: Iridium oxide– coated defibrillation electrode: reduced shock polarization and improved defibrillation efficacy. Circulation 96:3732-3736, 1997.

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106. Niebauer MJ, Yamanouchi Y, Hills D, et al: Voltage dependence of ICD lead polarization and the effect of iridium oxide coating. Pacing Clin Electrophysiol 23:818-823, 2000. 107. Sweeney MO: Exploding implantable cardioverter defibrillator. J Cardiovasc Electrophysiol 12:1422-1424, 2001. 108. Hauser RG, Almquist AK: Learning from our mistakes? Testing new ICD technology. N Engl J Med 359:2517-2519, 2008. 109. Klug D, Balde M, Pavin D, et al: Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Circulation 116:1349-1355, 2007. 110. Cooper JM, Sauer WH, Garcia FC, et al: Covering sleeves can shield the high-voltage coils from lead chatter in an integrated bipolar ICD lead. Europace 9:137-142, 2007. 111. Zartner PA, Wiebe W, Toussaint-Goetz N, Schneider MB: Lead removal in young patients in view of lifelong pacing. Europace 12:714-718, 2010. 112. Wazni O, Epstein LM, Carrillo RG, et al: Lead extraction in the contemporary setting: the Lexicon Study: an observational retrospective study of consecutive laser lead extractions. J Am Coll Cardiol 55:579-586, 2010. 113. Hauser RG, Katsiyiannis WT, Gornick CC, et al: Deaths and cardiovascular injuries due to device-assisted implantable cardioverter-defibrillator and pacemaker lead extraction. Europace 12:395-401, 2010. 114. Saad EB, Saliba WI, Schweikert RA, et al: Nonthoracotomy implantable defibrillator lead extraction: results and comparison with extraction of pacemaker leads. Pacing Clin Electrophysiol 26:1944-1950, 2003. 115. Rinaldi CA, Simon RD, Geelen P, et al: A randomized prospective study of single-coil versus dual-coil defibrillation in patients with ventricular arrhythmias undergoing implantable cardioverter defibrillator therapy. Pacing Clin Electrophysiol 26:16841690, 2003. 116. Cooper JM, Stephenson EA, Berul CI, et al: Implantable cardioverter-defibrillator lead complications and laser extraction in children and young adults with congenital heart disease: implications for implantation and management. J Cardiovasc Electrophysiol 14:344-349, 2003. 117. Wilkoff BL, Belott PH, Love CJ, et al: Improved extraction of ePTFE and medical adhesive modified defibrillation leads from the coronary sinus and great cardiac vein. Pacing Clin Electrophysiol 28:205-211, 2005. 118. Koplan BA, Weiner S, Gilligan D, et al: Clinical and electrical performance of expanded polytetrafluoroethylene–covered defibrillator leads in comparison to traditional leads. Pacing Clin Electrophysiol 31:47-55, 2008. 119. Hackler JW, Sun Z, Lindsay BD, et al: Effectiveness of implantable cardioverter defibrillator lead coil treatments in facilitating ease of extraction. Heart Rhythm 7:890-897, 2010. 120. Undavia M, Fischer A, Mehta D: Fatal outcome in a pacemakerdependent patient. Pacing Clin Electrophysiol 32:550-553, 2009. 121. Fahy GJ, Kleman JM, Wilkoff BL, et al: Low incidence of leadrelated complications associated with nonthoracotomy implantable cardioverter-defibrillator systems. Pacing Clin Electrophysiol 18:172-178, 1995. 122. Roelke M, O’Nunain SS, Osswald S, et al: Subclavian crush syndrome complicating transvenous cardioverter-defibrillator systems. Pacing Clin Electrophysiol 18:973-979, 1995. 123. Kron J, Herre J, Renfroe EG, et al: Lead- and device-related complications in the antiarrhythmics versus implantable defibrillators trial. Am Heart J 141:92-98, 2001. 124. Kupper B, Yee R, O’Hara G, et al: Do small (6.6 Fr) active and passive fixation defibrillation leads perform as well as larger sized leads? A multi-centre analysis. Europace 9:657-661, 2007. 125. Hauser RG, Kallinen LM, Almquist AK, et al: Early failure of a small-diameter high-voltage implantable cardioverterdefibrillator lead. Heart Rhythm 4:892-896, 2007. 126. Krahn AD, Champagne J, Healey JS, et al: Outcome of the Fidelis implantable cardioverter-defibrillator lead advisory: a report from the Canadian Heart Rhythm Society Device Advisory Committee. Heart Rhythm 5:639-642, 2008. 127. Faulknier BA, Traub DM, Aktas MK, et al: Time-dependent risk of Fidelis lead failure. Am J Cardiol 105:95-99, 2010. 128. Beukema RJ, Misier AR, Delnoy PP, et al: Characteristics of Sprint Fidelis lead failure. Neth Heart J 18:12-17, 2010. 129. Hauser RG, Hayes DL: Increasing hazard of Sprint Fidelis implantable cardioverter-defibrillator lead failure. Heart Rhythm 6:605-610, 2009. 130. Porterfield JG, Porterfield LM, Kuck KH, et al: Clinical performance of the St. Jude Medical Riata defibrillation lead in a large patient population. J Cardiovasc Electrophysiol 21:551-556, 2010. 131. Cannom DS, Fisher J: The Fidelis recall: how much pressure can the ICD world bear? Pacing Clin Electrophysiol 31:1233-1235, 2008.

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5 

SECTION 1  Basic Principles of Device Therapy

Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring CHU-PAK LAU  |  CHUNG-WAH SIU  |  HUNG-FAT TSE

Implantable sensors monitor changes in the body’s physiologic con-

ditions. Detection of pathophysiologic changes has been used either to modify the pacing rate of a rate-adaptive pacing system or to allow continuous monitoring of medical conditions such as heart failure or ischemia. This chapter reviews the principles and types of sensors that have been investigated and their clinical applications.

SENSORS FOR RATE-ADAPTIVE PACING Basis of Sensor-Driven Pacing Chronotropic incompetence may occur in up to 30% of patients with sinus node disease. It may also develop over time as a result of degeneration, medications, or comorbidities. In addition, for patients whose atrium is unreliable for pacing, such as during atrial fibrillation, an alternative means is required to simulate the response of the sinus node to exercise or emotion. Implantable sensors for cardiac pacing allow a pacing system to respond to exercise and nonexercise requirements for an increase in heart rate. Sensors are now a programmable option of almost all bradycardia pacemakers. Atrioventricular (AV) synchrony enhances cardiac output by augmenting the stroke volume by 20% to 30% during exercise. However, this increase is relatively small compared with the threefold to fourfold increase achieved by an increase in heart rate. The relative contribution of AV synchrony and rate increase in patients with complete AV block was studied in dual-chamber (DDD) and a rate-matched ventricular pacing (VVI) mode.1 At rest, the cardiac output during DDD pacing was 18% higher than during VVI pacing because of AV synchrony. During exercise, however, the net cardiac output was only 8% higher during DDD pacing compared with VVI pacing at an identical rate. An equivalent exercise capacity was reported in another study,2 and both DDD and rate-matched VVI pacing were superior to fixed-rate VVI pacing during exercise. Cardiac output was similar in the two modes at near-maximal exercise, but at lower workload levels, cardiac output was maintained by an increased arteriovenous oxygen saturation difference and arterial lactate level. In addition, systolic and mean blood pressures were lower when exercise was performed without AV synchrony. These findings suggest that rate response is the primary driver for exercise cardiac hemodynamics, with a much smaller contribution of AV synchrony. EXERCISE RESPONSE IN HEART FAILURE In a patient with heart failure, because the left ventricular (LV) filling pressure is elevated and the heart is working at the flat portion of the Frank-Starling curve, an increase in heart rate is the most important means to increase the cardiac output. In a study of 22 patients with poor LV function and implanted rate-adaptive pacemakers, the benefit of rate adaptation to exercise capacity was greatest in those with the poorest LV function.3 In patients with implanted cardiac resynchronization therapy (CRT) devices,4 chronotropic incompetence (maximum heart rate 0.9 in first-, second-, and third-order polynomial equations).17 Furthermore, the calibration between measured MV and impedance MV changes over time (1 week to 1 month). However, the changes were not correlative, with implications for the need of continual automatic adaptation. These findings also suggest the potential use of the sensor for MV monitoring. Boston Scientific (Pulsar Max, Insignia, Altrua).  In the Boston Scientific devices, MV is available in conjunction with an accelerometer sensor, although either sensor can be used alone or blended with the other. MV collected by the atrial or ventricular lead (programmable) over 24 hours is used as an average against which future changes in MV are compared for a rate response. The minimum time for achieving a baseline is 4 minutes (“4 → On”). A linear response curve is used, and a total of 16 response factors can be chosen below the pacing rate estimated for anaerobic threshold. This rate is also programmable. In between the pacing rate for anaerobic threshold and the maximum predicted heart rate, a gentler “high rate response” can be programmed. The adaptation can be made faster by activating the 4-minute walk within 30-minute option, in which the subject is instructed to exercise to achieve the maximal MV change. The telemetered MV impedance signal from a Boston Scientific device was compared with measured MV in 20 patients.18 Respiratory rate was accurately measured by the device during hyperventilation, with difference less than 0.2 breath/min. During 10-minute cycle ergometry at 50 W, the correlation between MV measured directly and by the device was 0.99. Large, individual variations exist between the measured MV and the impedance MV slope, requiring individualized rate-response curves. ELA-Sorin (Chorus, Talent, Opus, Symphony, Rhapsody, Reply).  Minute ventilation is determined from a default bipolar atrial lead, with current injection from distal electrode to casing, and current collection between the proximal pole and casing. In the event of a unipolar atrial lead, the distal electrode of the ventricular lead is used as the current-injecting electrode. Sourcing and injection can also be performed with a bipolar ventricular lead. The automatic slope algorithm in the Chorus determines the resting and maximum MV values daily. If MV over 128 cycles remains below the 24-hour MV average, the lower rate will decrease to the LRL. The device calculates the exercise MV signal by looking for the maximal MV signal and recalculates this value every eighth cycle. The exercise MV value is increased or decreased in 6% intervals. The mean resting and exercise MV values are used to adjust the rate-response slope automatically over the range of values from 1 to 15 in steps of 0.1. The response of the Talent DR during exercise was compared in 81 patients. The correlation coefficient between the sensor rate and programmerderived sensor rate was 0.983 ± 0.005, and a linear relationship was observed between the heart rate reserve and MV reserve.19 Clinical Experience of MV Sensor Pacemakers Minute ventilation is an indirect but reliable marker of metabolic demand, and in the first generation of MV pacemakers (Meta MV, Telectronics), the rate response was proportional to the level of

SECTION 1  Basic Principles of Device Therapy

Limitations of Minute Ventilation Sensing As with all impedance systems, the MV sensor will likely be affected by electromagnetic interference, arm swinging, coughing, and hyperventilation.16 Artificial ventilation will induce an unphysiologic rate, so MV sensing needs to be disabled in such patients (e.g., general anesthesia, mechanical ventilation). The use of MV devices in patients with lung disease and heart failure remain controversial. Early generations of MV-sensing devices limited the maximum detectable respiratory rates to less than 48 to 60 breaths/min to minimize the cardiac effects of changes in impedance. Because of this filtering of the cardiac component of changes in impedance, MV sensors may not accurately reflect rate adaptation at very high respiratory rates, as may occur in children. A bipolar ventricular lead is needed for MV sensing in several models. The battery current for MV sensing may consume approximately 2% of the total current of a dual-chamber pacemaker. Some amplifiers may sense the small impedance pulses unless preventive steps are taken. In some products, a blanking period of about 1 msec is applied to the amplifiers to “blind” them to these pulses. In other cases, special balancing of the pulse achieves the same objective. Sensing of the impedance pulses by a surface electrocardiogram (ECG) monitor may occur, depending on the ECG machine’s frequency response as well as pulse width and balancing of the impedance pulse. Also, frequencies above a few kilohertz (kHz), such as generated by electrocautery and electrosurgery, are detected by the rate-response circuitry and could drive an MV-sensing pacemaker to its maximum rate. It is recommended that the rate-response function be inactivated whenever electrosurgery will be used. Respiration may also be influenced by phonation and coughing that have no direct relevance to change in cardiac output. UNIPOLAR VENTRICULAR IMPEDANCE: CLOSED-LOOP STIMULATION SENSOR Contractility of the right ventricle increases during catecholamine stimulation, as occurs in exercise and emotional stress. In the absence of an adequate rate response, exercise will induce a higher contractility. When rate response is adequate, the change in contractility is less, thus establishing a negative feedback loop and a new, steady contractility state. On the other hand, elevated pacing rates can increase contractility, the so-called Treppe effect, although this has not been important in clinical practice. Right ventricular (RV) impedance can be derived from a standard pacing lead and can be used to monitor heart function and catecholamine state. Sensor and Algorithm The CLS sensor is based on unipolar impedance at the tip of a pacing lead.22 Subthreshold pulses of automatically selected outputs, ranging from 100 to 400 microamperes (µA), with biphasic duration of 46 msec are emitted 50 to 300 msec after a sensed or paced ventricular event. During late diastole immediately after a ventricular paced (Vp)

or sensed (Vs) event, the blood volume of the right ventricle is highest and RV impedance is lowest. On the other hand, as contraction occurs, the walls surrounding the electrode tip draw closer, and impedance rises (Fig. 5-7, A). A baseline waveform will depend on the conduction state of the heart: AsVs, AsVp, ApVs, ApVp (As, atrial sensed; Ap, atrial paced event). Baseline CLS waveforms will be acquired only when the associated accelerometer indicates “no activity,” and a waveform will be discarded within 48 hours if not referenced. An average template of the baseline CLS waveform will take 2 to 3 days to optimize. As contractility increases during exercise, unipolar impedance will change. The time-integrated difference between the exercise and baseline impedance waveforms is converted to a pacing rate using an auto response factor, which is continually adapted and patient specific. The magnitude of rate response is then determined by a programmable exertion threshold rate (ETR; very low, low, medium, high, and very high) (Fig. 5-7, B). The ETR, acting through the auto response factor, will determine that 80% of the heart rate will occur below the ETR and 20% above the ETR. An active young individual will probably require a higher ETR than an inactive elderly patient. Again, the type of rate profile attained will be determined by the patient’s cardiac condition, physical state, and specific automatic response factor. Although not strictly a dual-sensor pacemaker, the incorporated accelerometer performs an “on-off ” function to decide on the acquisition of the baseline CLS waveform and the CLS-driven response. Full CLS-driven rate according to the programmed ETR will be allowed only if the accelerometer registers “exercise”; otherwise, only 20 bpm above the LRL is allowed to enable a nonexercise rate increase. In neurocardiogenic syncope, this rate-limiting algorithm can be inactivated for full overdrive response, as during a syncopal episode. TIME (ms) 240 Resting

200 Units

exertion and correlated with the normal sinus response.20,21 Compared with VVI pacing, MV-based VVIR pacing increased exercise capacity by 33%,21 and maximal oxygen consumption and cardiac output were significantly improved. In one study of 10 patients with the first version of MV-driven VVIR pacing, pacing rate was highly correlated with measured MV (r = 0.89), respiratory quotient (r = 0.89), Vco2 (r = 0.87), tidal volume (r = 0.87), Vo2 (r = 0.84), and respiratory rate (r = 0.84). Maximum oxygen consumption also increased from 13.4 ± 3.4 to 16.3 ± 4.1 mL/kg/min (P = .0004) using MV-driven over VVI pacing. Improvement in symptoms were also documented in the VVIR mode.21 The MV sensor has good long-term stability; programming of the sensor is relatively simple; and the rate response is appropriate during daily activities. Compared with activity pacing, MV is significantly better in achieving a near-normal pacing rate–workload relationship, whereas activity sensing tends to overpace at low-level exercise and underpace at peak exercise and in the recovery period.

160 120

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80 40 50

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100

150

200

250

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Milliseconds after a sensed or paced ventricular event 8

ETR = 73

7 6 Rate (%)

150

ETR = 80

ETR = 92

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5 4

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60

70

80

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Figure 5-7  Closed-loop stimulation (CLS) sensor and algorithm. A, Changes in CLS parameter during exercise. Hatched area represents the difference between baseline and exercise CLS waveforms and is converted to a rate using the exertion threshold rate (ETR). B, Impact of ETR on rate response of CLS. “Medium” ETR corresponds to a rate of 80 beats per minute (bpm; 20 bpm above lower rate limit). Programming this rate will ensure a rate response of 80% less than this rate and 20% above this rate. A higher or lower ETR will result in different rate responses.



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

151

Micro mass PEA Pace/sense Electronics Figure 5-8  Biomechanical Endocardial Sorin Transducer. The BEST sensor (Sorin Biomedica Cardio) consists of a microaccelerometer located inside a rigid capsule at the tip of a standard ventricular pacing lead, which is connected to a triple header. PEA, Peak endocardial acceleration.

Current Closed-Loop Stimulation Devices: Biotronik (Inos, Protos, Cyclos, Entovis, Evia) Acute measurements of the CLS parameter (previously known as “ventricular inotropic index”) were taken in 82 patients with chronically implanted unipolar ventricular leads at pulse generator replacement.22 A wide fluctuation of baseline impedance was observed (500-1500 Ω), whereas CLS fluctuated by about 4 to 25 ohms (Ω), with a good correlation between CLS and the baseline impedance. A clinical study of 205 patients evaluating the CLS pacemaker included a significant number of young subjects with complete AV block caused by Chagas’ disease.23 Satisfactory rate modulation was reported in 93% of patients. In the remaining 7% of patients, rate adaptation could not be achieved because of poor exercise tolerance, severe myocardial dysfunction, and intermittent intrinsic AV conduction. In a multicenter study that included 178 VVIR (Biotronik Neos-PEP) and 84 DDDR (Biotronik Diplos-PEP, InosDR) devices, physiologic rate adaptation was possible in 93% and 96% of patients with these devices, respectively.24 Apart from exercise rate response, this study also involved mental stress testing using color-word matching and the infusion of inotropic agents. A moderate level of rate response was documented in some patients with CLS pacemakers during these nonexercise conditions that was greater than during accelerometer-guided pacing. The benefit of CLS sensor pacing during mental stress and cognitive function has also been studied.25 Considerable interest surrounds the use of the CLS sensor to detect changes in posture. Passive head-up tilt, which depletes intravascular volume, increases the inotropic state of the heart. In a multicenter study, Inotropy Controlled Pacing in Vasovagal Syncope (INVASY), 50 patients with severe vasovagal syncope and positive head-up tilt test were randomized between DDD-CLS and DDI mode at 40 bpm.26 Whereas 7 of 9 patients in the DDI arm experienced syncope within 1 year, only 4 of 41 patients in the DDD-CLS arm had presyncope. The authors suggested the efficacy of this approach, although a placebo effect of pacing was suspected in 22% of patients. In 131 patients with chronotropic incompetence, CLS pacing resulted in a higher pacing rate compared with accelerometer sensor, but no difference in 6-minute walking distance (6MWD) test.27 However, twice as many patients preferred the CLS mode. The use of CLS in the left ventricle, as in a CRT device for monitoring, may be a useful application of this technology (see later discussion).

PEAK ENDOCARDIAL ACCELERATION Sensor and Algorithm The contractile state of the heart can be identified by the maximal velocity of shortening of unloaded myocardial contractile elements, which can be measured with a catheter tip accelerometer attached to the ventricular wall. The “peak endocardial acceleration” represents the endocardial vibration measured by the accelerometer in the right ventricle during isovolumetric contraction phase of the ventricles. This signal is closely associated with the intensity of the first heart sound. The ELA-Sorin BEST (Biomechanical Endocardial Sorin Transducer) sensor is a microaccelerometer consisting of an acceleration sensor built into a nondeformable capsule on the tip of a standard unipolar ventricular pacing lead. The lead is placed against the RV wall so as to be sensitive to its acceleration and insensitive to the pressure of blood and myocardium (Fig. 5-8). This system has a frequency response up to 1 kHz and a sensitivity of 5 mV/G (1 G = 9.8 m/sec/sec). In early animal experience using an external system and an implantable radiotelemetry system, the PEA was not affected by heart rate but significantly increased by emotional stress, exercise stress testing, and inotropic stimulation.28 The PEA signal changes in parallel to the maximal LV dP/dt and appears to measure the global LV contractile performance rather than the regional mechanical function. The PEA signal that occurs 150 msec after the R wave corresponds to the isovolumetric contraction phase of the left ventricle (PEA-I)29 (Fig. 5-9). A smaller signal also occurs in the 100-msec period after the T wave,

ECG

LV dP/dt

Ao Press

LV Press

Advantages and Limitations Closed-loop stimulation appears to be a good sensor to measure cardiac contractility using a conventional ventricular pacing electrode. The demand on pacing energy is acceptable. As a contractility sensor, CLS is sensitive not only to exercise but also to nonexercise requirements, and it may therefore be used for monitoring cardiac contractility for non–rate augmentation purposes. CLS can be used only in a pacing mode that incorporates a ventricular lead. Ventricular ischemia and cardioactive medications likely influence CLS rate adaptation, although automatic adjustment may permit long-term function. A small proportion of patients are not suitable for CLS sensors because of severely impaired RV function. Such patients may be identified preoperatively, and a backup activity sensor is always available.

EA PEA-I

PEA-II

Figure 5-9  BEST tracings. Electrocardiogram (ECG), left ventricular (LV) dP/dt, aortic pressure (Ao Press), LV pressure, and endocardial accelerometer tracing (EA) recordings in a sheep with the BEST sensor (see Fig. 5-8). The peak of the accelerometer tracing during the isovolumic diastole (PEA-II) occurs in a 100-msec period after the T wave on the ECG. (From Plicchi G, Mercelli E, Parlapiano M, et al: PEA-I and PEA-II based implantable haemodynamic monitor: preclinical studies in sheep. Europace 4:49, 2002.)

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SECTION 1  Basic Principles of Device Therapy

the so-called PEA-II, which corresponds to the isovolumetric LV relaxation. PEA-II is related to peak negative dP/dt (r = 0.92) and aortic diastolic pressure (r = 0.91).30 To enable the PEA sensor to be used in patients requiring an ICD lead, the sensor has been incorporated into a right atrial (RA) lead (SonR sensor). Preliminary results suggest that the SonR sensor is similar to the RV PEA signal and that it might be useful in patients receiving cardiac resynchronization therapy with defibrillation (CRT-D).29 This offers the potential to measure cardiac hemodynamics in heart failure patients with an ICD. Current PEA Devices: BEST Sensor Rate–Adaptive Pacemakers (Sorin Best-Living Systems: Miniliving D and S) These PEA devices use a dedicated unipolar ventricular pace/sense lead, which is IS-1 compatible. Together with the two electrodes for PEA signals, a tripolar connector is necessary. These devices also incorporate an activity sensor detecting the vibration (gravitational sensor). In the PEA mode, continuous PEA signal collected over time is used as a reference, against which the change in PEA is compared. A linear pacing rate response curve is used to relate the change in PEA signal and the rate response. In the dual-sensor mode, the combined output from both sensors is used to drive the rate to an intermediate level, and further rate increases are guided by the PEA sensor alone. In addition, prolonged absence (about 45 minutes) of signals from both the gravitational and the PEA sensor will allow the basic rate to decrease to the programmable rest rate. Clinical Results Clinical studies show good correlation between the sinus rate and PEA sensor–indicated rate during daily life activities and submaximal stress testing.31,32 Similar results were obtained in patients tested during electrophysiologic studies using an external system; changes in PEA were linearly related to the RV dp/dt during dobutamine infusion. PEA signals have been used to monitor hemodynamic function and program the A-V interval. In 13 patients with end-stage heart failure implanted with a DDD-PEA device with a custom lead arrangement, PEA level during RV, LV, and biventricular (BiV) pacing were compared.32 Both LV and BiV pacing increased stroke volume (21% and 37%, respectively) compared with RV pacing, and mean PEA changes over 15 minutes were also higher (43% and 38%). In addition, an apparent minimum PEA level at the optimal A-V interval has shown promise in automatically detecting the optimal A-V interval in a dual-chamber device.33 The algorithm is now automatic. An increase in PEA during head-up tilt-table testing has been observed, and the use of PEA-driven overdrive pacing in patients with vasovagal syncope has been reported.34 Patients randomized to DDDR have a reduced frequency of syncope compared with DDI pacing. In 15 patients with a CRT pacemaker, the PEA correctly indentified the optimal AV interval in 75% of patients.35 These data suggest the potential use of PEA sensor for hemodynamic monitoring (see later). Advantages and Limitations PEA is a proportional sensor that shows good correlation to cardiac workload, especially at higher ranges. The PEA sensor is limited by the need for a specialized lead, leading to concerns about its long-term stability and its use at pacemaker replacement (when a standard header pacemaker is used). Development of the PEA sensor in an atrial lead allows its use in patients requiring an ICD lead.

Current Combined Sensor Devices Experience with sensors has suggested that rapidly responding sensors (e.g., activity) are not proportional at higher levels of cardiac workload, whereas proportional sensors are usually slow in response. As a result, an activity sensor overpaces at low activity levels but underpaces at higher exertional levels (Fig. 5-10). Furthermore, single sensors may be limited by insensitivity to nonexercise stress and are prone to

interference by nonphysiologic causes. Thus, it is logical to enhance their rate-response profile by combining two or more sensors. Two principles guide the combining of sensors: sensor blending and sensor cross-checking. Sensor blending involves combining sensordriven rates from individual sensors in a certain ratio. This can be the “faster win” method, in which the higher rate indicated by either sensor is chosen as the pacing rate, or ratios of the individual rates are added together to compute the actual rate response. Sensor cross-checking enhances the specificity of each sensor. If a more specific sensor registers “no exercise” or physiologic stress, changes in the other, less specific sensor can be ignored or its response attenuated (Fig. 5-11). Table 5-3 summarizes instrumentation of current dual-sensor devices. Details of the combined CLS/activity and PEA/activity devices are discussed earlier. CURRENT DUAL-SENSOR DEVICES Medtronic Pacemakers Medtronic marketed two dual-sensor pacemakers: the combined activity and QT sensors (Vitatron) and the combined activity and MV sensors (Kappa 400). Both are no longer manufactured. In the activity/ QT device, a “faster win” algorithm was used, with highest rate of two sensors used to determine actual pacing rate. Since the QT sensor is more specific for physiologic changes, an increase in activity sensor level in the absence of QT documenting exercise was used as a crosscheck, resulting only in a brief and limited rate response. Using an adaptive sensor level to the SURL, the QT sensor level was continuously scaled down if, at the SURL, QT continued to shorten, suggesting the sensor level had reached the upper rate too soon. The converse was also operative. The combined sensor rate was found to be closer to the sinus rate during daily activities.36 In the Kappa 400, a piezoelectric sensor is used for activity sensing, and MV is sensed from a bipolar ventricular lead. Differential sensor blending is used. Up to the ADL rate, activity input predominates, whereas MV-driven pacing will predominate at the SURL. Activity and MV sensors were checked against one another. In the absence of piezoelectric sensor indicating exercise, MV pacing only reached the ADL rate, and vice versa. Only when both MV and activity signified exercise would pacing occur above the ADL rate. The dual-sensor rate response has been reported to be reliable for both maximal and submaximal activities, as well as resistant to nonphysiologic interference.37 Compared with MV sensor alone, dualsensor mode reduces oxygen deficit acquired during exercise by enhancing the initial rate response.38 “Quantitative rate adaptation” is also superior in the dual-sensor mode.39,40 “Rate profile optimization” was found to be a useful method for rate-adaptive programming, comparable to manual programming,41 and may be superior to accelerometer alone for rate optimization.11 Boston Scientific (Insignia, Pulsar Max, Altrua) An accelerometer activity sensor is integrated with the MV sensor, using differential sensor blending. At low heart rates, the blended sensor rate is approximately 80% accelerometer and 20% MV sensor. This ratio changes to 40%/60% near the SURL. In addition, if the MV rate is higher than the accelerometer rate, the dual-sensor rate follows the MV level. In a study involving 120 patients with Insignia, the programmed sensor modes were randomized to the accelerometer sensor alone, the MV sensor alone, or the dual-sensor mode, each for a 3-month period.42 Using the implanted Activity Log to determine the mean percentage and intensity of activity, quality of life (QOL), and New York Heart Association (NYHA) classes were assessed at the end of each period. Overall, either single-sensor DDDR mode improved Activity Log, QOL, and NYHA scores compared with DDD pacing, but with no difference between the two sensors. The dual-sensor mode did not improve these measurements. This study may have been limited by the prolonged, triple-crossover design but does suggest that clinical differences are likely minimal between sensors and their combinations.



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring 1.00

1.0

HR (normalized)

Observed

Expected Quartile 1 137%

0.25 Quartile 2 81%

Quartile 3 66%

A

0.25

0.50

1.00 Max VO2

0.75

Observed

1.0 Total area 122%

0.8

0.6

HR (normalized)

0.4 Quartile 3 100%

0.4

0.2

0.0

Metabolic equivalents (normalized)

Total area 30%

0.8

0.6

Quartile 2 166%

0.8

1.0

Expected

Observed

Quartile 1 352%

1.0

B

Metabolic equivalents (normalized)

HR (normalized)

Expected 0.4

0.0

0.00 Min VO2

0.6 Expected 0.4

Observed

0.2

Quartile 4 75%

0.0

0.0

0.00 Min VO2

C

0.6

0.2

Quartile 4 102%

0.00

0.2

Total area 85%

0.8 HR (normalized)

Total area 89%

0.75

0.50

153

0.25

0.50

0.75

1.00 Max VO2

Metabolic equivalents (normalized)

1.0

D

0.8

0.6

0.4

0.2

0.0

Metabolic equivalents (normalized)

Figure 5-10  Quantification of pacing percentage of minute volume (MV) and activity pacer during graded treadmill exercise. A, Results of the normalized heart rate and workload in one patient. There is overpacing in quartile 1 (137%), underpacing in quartiles 2 (81%) and 3 (66%), and near-ideal pacing in quartile 4. B, Near-ideal rate recovery of the MV sensor. C and D, Exercise response of an activity sensor, with overpacing most of the time, but inadequate rate recovery. (From Kay GN: Quantitation of chronotropic response: comparison of methods for rate-modulated permanent pacemakers. J Am Coll Cardiol 20:1533, 1992.)

TABLE

5-3 

Types of Dual-Sensor Pacemakers in Current Use

Manufacturer Medtronic

Models Kappa 400

Sensors ACT: piezoelectric MV: impedance

Algorithms Blending ≤ADL range: ACT + MV ADL-ER range: mainly ACT

Boston Scientific

Pulsar Max Insignia Altrua

ACT: accelerometer MV: impedance

ELA-Sorin

Chorus Talent Symphony Rhapsody Talos Cylos Entoris

ACT: accelerometer MV: impedance

Blending Low heart rate: ACT 80%, MV 20% High heart rate: ACT 40%, MV 60% No blending MV-determined rate response if ACT indicates exercise No blending No ACT rate contribution Rate response determined only by CLS

Biotronik

CLS: unipolar ventricular impedance ACT: accelerometer

Cross-checking ACT (0) and MV (+): up to ADL rate ACT (+) and MV (0): up to ADL rate ACT (0) and MV (+); and ACT (+) and MV (0): limited rate ACT (+) and MV (0): initial limited rate response ACT (0) and MV (+): rate recovery ACT (0) and CLS (+): limited rate response ACT (+) and CLS (0): no rate response

Automaticity Rate Profile Optimization

AutoLifestyle

Automatic matching MV sensor to LRL and SURL Auto Response Factor adjusts CLS data to reach rate distribution determined by the programmed Exertion Threshold Rate

ACT, Activity level; ADL, activity of daily living; CLS, closed-loop stimulation; ER, exertion response; LRL, lower rate limit; MV, minute ventilation; SURL, sensor-driven upper rate limit.

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SECTION 1  Basic Principles of Device Therapy

TABLE

SR

5-4 

Select Patients for Dual-Sensor Pacemaker

Clinical Situation High exercise heart rate preferred

S1

Avoidance of undue rate acceleration Need for nonexercise rate response

S2

Examples Young, athletic individuals may require a more physiologic sensor. Working in a vibrational environment Vasovagal syncope Stress response

Hemodynamic or other monitoring

Exercise

Nonexercise stress

Interference

Proportionality and speed

Sensitivity

Specificity

Figure 5-11  Algorithms for sensor combinations needed to achieve better proportionality and speed of response, sensitivity, and specificity. Top to bottom, Graphs depict the responses of the sinus node (SR), sensor 1 (S1), sensor 2 (S2), and combined rate profile (S1 + S2). SR shows ideal proportionality, speed of rate response, and freedom from interference. S1 is a rapidly responding sensor, although it is neither proportional nor sensitive and is susceptible to interference. S2 is a proportional and sensitive sensor, although it has a slow response. It is also specific to exercise. Note the improved ability of the combined sensor approach in simulating the sinus rate under different conditions.

The Limiting Chronotropic Incompetence for Pacemaker Recipients (LIFE) study of 1256 patients with chronotropic incompetence found that the blended sensor improved metabolic-chronotropic slope compared with the activity sensor alone43 (Fig. 5-12). However, besides improved physical activity time/energy expenditure, there was no measurable difference in QOL between the blended sensor and the activity sensor alone. A prospective randomized parallel study on activity and MV with the primary outcome of Vo2 is planned (APPROPRIATE study).44 This study will randomize 1000 patients who will be screened for CI using a 6MWD and treadmill heart rate at 1 month. Patients with confirmed CI will have their sensors optimized with a brief walking test. Apart from Vo2 max, rate changes during daily activities will be assessed. This study will shed light in the role of different sensors on exercise oxygen uptake. (Unfortunately, the study was prematurely terminated because of suboptimal recruitment.) ELA-Sorin (Chorus, Talent, Symphony, Rhapsody, Reply) An accelerometer and a MV sensor are combined in these devices. Sensor blending and cross-checking are both operative to effect rate adaptation during exercise (Fig. 5-13). When the accelerometer is active but MV has not increased, as may occur at the beginning of exercise, rate response occurs according to a fixed activity response curve to a limited rate. When MV increases, rate response follows the MV sensor–driven rate. Persistent absence of accelerometer signal is considered the cessation of exercise, and this allows a decrease in the pacing rate using a recovery curve to the LRL, even though MV remains higher than baseline. A multicenter study involved 81 patients with the ELA dual-sensor pacemakers.19 In patients who underwent exercise stress testing at 1-month follow up, sensor-driven rate had good correlation with the sinus rate (r = 0.92 ± 0.07; P < .001), with the slope of linearity at 1.0 ± 0.2. Using metabolic reserve to relate to heart rate reserve, a slope of 1.1 ± 0.2 was obtained, suggesting a close relation between the dualsensor rate and metabolic workload. ARE DUAL SENSORS JUSTIFIED? Dual-sensor implementation is technically and clinically feasible and provides a rate profile closer to the normal sinus rate. In practice, a more specific sensor is added to the activity sensor to enhance its

specificity. However, apart from physiologic parameters such as oxygen uptake and transport kinetics, no clinical benefit over single sensor has been seen in large groups of patients, likely reflecting the limited exercise activities of most patients meeting standard indications for pacing. For select patients who are highly active, however, these dual-sensor pacemakers may provide important clinical benefits (Table 5-4).

Clinical Benefits of Sensor-Driven Pacing Controversy remains about the clinical benefits of sensor-driven pacing, especially the lack of symptomatic benefit observed in some comparative studies. Factors that may affect such comparisons include (1) definition of CI, (2) programming of sensor (extent of rate adaptation), (3) patient populations including their comorbidities, (4) pacing modes, and (5) site of ventricular pacing (Table 5-5). CHRONOTROPIC INCOMPETENCE Although factors contributing to CI can be obvious—age, coronary artery disease, sinus node dysfunction, and cardioactive medications— what constitutes CI remains uncertain. CI can vary from 9% to 84%, MCR SLOPE

1.0

Heart rate reserve (%)

S1 + S2

0.8 p 3

Days with intrathoracic impedance fluid index above threshold (yr–1)

Figure 5-30  Comparison (Poisson regression) of acute decompensated heart failure (ADHF) hospitalization rates between groups of subjects. A, Subjects with no intrathoracic impedance fluid index threshold crossing events (TCEs; n = 197), subjects with one to three TCEs (n = 79), and subjects with more than three TCEs (n = 28). B, Subjects with 0 (n = 1910), subjects with 1 to 30 (n = 31), and subjects with more than 30 (n = 82) intrathoracic impedance fluid index threshold crossing days per year. Error bars indicate 95% confidence intervals. (From Small RS, Wickemeyer W, Germany R, et al: Changes in intrathoracic impedance are associated with subsequent risk of hospitalizations for acute decompensated heart failure: clinical utility of implanted device monitoring without a patient alert. J Card Fail 15:475-481, 2009.)

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SECTION 1  Basic Principles of Device Therapy

Advantages and Limitations

TABLE

Intrathoracic impedance is one of the most extensively used sensors for monitoring heart failure. Its advantages include the relative ease of instrumentation, requiring no additional leads or complex implantation. The battery energy expenditure is low. Intrathoracic impedance has been relatively well characterized in acute setting and for long-term monitoring. Although sensitive, its specificity may be limited because impedance in the vector used may be affected by clinical events that do not indicate pulmonary congestion, such as pleural effusion109 (Table 5-8). INTRACARDIAC IMPEDANCE Impedance signals derived from fully intracardiac electrodes better reflect cardiac volume changes than transthoracic impedance. Indeed, Salo et al.110 reported the use of a tripolar RV lead to measure RV volume changes during the cardiac cycle, from which RV volume and contractility can be derived for rate-adaptive pacing. With the addition of an LV lead in CRT, more accurate measurement of LV volume is now possible for heart failure monitoring. Unipolar Impedance from Right Ventricle Unipolar impedance from the RV apex to the CIED casing samples a small region in the cardiac apex. This results in a signal recorded by the closed-loop stimulation (CLS) sensor (see earlier). Because most current is lost over a distance of about 1 cm from the apex, the signal reflects regional contractility of the ventricle rather than a change in stroke volume. While during acute induction of ventricular fibrillation, the fall in unipolar RV impedance reflects the fall in arterial pressure, the sensitivity is insufficient to discriminate between hemodynamically stable ventricular tachycardia and supraventricular tachycardia.111 These results suggest that unipolar impedance reflects LV contractility only when the changes are significant, and it may not be able to detect small changes in cardiac contractility, as in heart failure monitoring. Multipolar Impedance Several groups and manufacturers have investigated the optimal electrode arrangement for detecting ventricular volumes. With currents flowing between intracardiac electrodes (RV, LV, and RA) and to the CIED casing, enlargement in ventricular volumes will decrease impedance as more of the heart is encompassed. Examining four intrathoracic and two intracardiac vectors in 16 dogs and five sheep, Panescu et al.112 monitored cardiac function with biweekly cardiac catheterization and echocardiography and LA pressure with an implantable

5-8 

Mechanism Blood viscosity Extrapulmonary changes Right-sided heart failure Pulmonary changes

35

–30

LV-Can LAP LV-RV

–25

LV-RA

–20

RV-Can RVcolCan

30 25

–15 –10

20 15 10

–5

RA-Can

0 –7 –6

3 4 5 6 7 8 9 10 11 12 13 14 15 16 Days

5

LAP (mm Hg)

Start of RV pacing

–35

Examples Anemia Pneumothoracic Pleural effusion Peripheral edema not detected Pneumonia

pressure sensor. After several weeks of high-rate pacing to induce heart failure, LVEF decreased significantly (52% to 34%), with increases in LV end-diastolic volume (65 to 97 mL), LV end-diastolic pressure (7 to 16 mm Hg), and LA pressure (7 to 26 mm Hg). Impedance value measured by all vectors decreased with the onset of heart failure (Fig. 5-31). The maximum decrease occurred with LV-can and LV-RV vectors. Importantly, LV-can impedance changes more with heart failure than vectors involving the right-sided heart electrodes (RA-can, RV-can, and RV coil-can), and RV-LV and LV-RA changes were intermediate. LA pressure correlated best with LV-can impedance (r2 = 0.73) than RV-can (r2 = 0.43) and RV coil-can (r2 = 0.52). Circadian variation in impedance also decreased in heart failure (5% ± 2% to 2% ± 1%). Thus, in these animal models, incorporation of an LV vector significantly improved the detection of LV volume increase in heart failure. Biventricular impedance has been measured using a quadripolar electrode arrangement.113,114 In nine mini-pigs with pacing-induced heart failure, biphasic pulses (15 µsec pulse width, 600 µA constant current amplitude) were injected between the RV ring and tip electrode, and impedance was sourced using the LV ring and tip electrode.114 The impedance signal (measured as voltage divided by 600 µA current) was recorded using 8-bite resolution, and the mean impedance was calculated over the entire cardiac cycle. “Stroke impedance” was calculated by the difference between impedance values during systole and diastole. “Systolic impedance” was defined as the highest impedance 50 to 500 msec after the R wave, whereas diastolic impedance was measured by a 20-msec window within the R wave. After 20 days of heart failure induction by rapid pacing in these animals, the increase in LV end-diastolic pressure was found to be significantly correlated with the end-diastolic impedance, which decreased by 30% (r = −0.81; P < .001). End-diastolic volume also trended in the same direction as the impedance value, which decreased by 20%. The corresponding measured intrathoracic impedance decreased by 8%, which had a poorer correlation with the end-diastolic pressure. The less striking change of intrathoracic impedance versus BiV-measured impedance might be attributed to the countering effect of lead/device

–40

Change in impedance (%)

Possible Causes of Increased OptiVol Fluid Index in Absence of Pulmonary Congestion

Figure 5-31  Impedance value measured by all vectors. Animal model shows left ventricular (LV) vector significantly improves detection of LV volume increase in heart failure. The changes in intracardiac impedance trend inversely with left atrial pressure (LAP). (From Panescu D, Naware M, Siou J, et al: Usefulness of monitoring congestive heart failure by multiple impedance vectors. Proc IEEE Eng Med Biol Soc 2008:5668-5670, 2008.)



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

TABLE

5-9 

Intrathoracic vs. Intracardiac (Biventricular) Impedance

Norm (ITZ)

1.05 Heart failure parameters Electrode arrangement

1

Lead/casing maturation Influence of lung disease Influence of lead location Circadian and postural effect Sensitivity and specificity

0.95

00:00 AM 04:00 AM 08:00 AM 12:00 PM 04:00 PM 08:00 PM Time of day Figure 5-32  Variation in intrathoracic impedance depends on time of day. In this animal model (pig #12), circles depict the 4-hour-averaged impedances as recorded by the pacemaker, normalized to the daily mean. Squares depict the means of summarized 4-hour averages. The line estimates diurnal variation by spline interpolation of the means. (From Stahl C, Beierlein W, Walker T, et al: Intracardiac impedance monitors hemodynamic deterioration in a chronic heart failure pig model. J Cardiovasc Electrophysiol 18:985-990, 2007.)

casing maturation, which did not occur with BiV impedance, and pulmonary fluid collection being relatively less in the porcine model of mild heart failure studied (Fig. 5-32). These animal experiments suggest that biventricular impedance can be used to monitor the LV size and pressure changes that occur with heart failure. The theoretical advantages over transthoracic impedance are no significant time lag for lead/pocket maturation and no influence of changes in pulmonary condition on impedance values (e.g., pleural effusion, pneumonia). Because LV end-diastolic pressure increases before pulmonary edema occurs, this sensor can be used to detect deterioration of early heart failure that has not resulted in significant pulmonary fluid accumulation, and to monitor LV function. The limitations include the need for an LV lead (which restricts its use to a CRT device), dependence on the relative position of RV-LV leads (only relative changes rather than absolute value can be detected), and significant diurnal (and possibly postural) changes that must be considered in an implantable system (see Fig. 5-32). Clinical Studies

AortaP (mm Hg) Z (ohm)

Figure 5-33  Biventricular (BiV) impedance in study of 14 heart failure patients. Example of raw data recording: ECG, surface electrocardiogram; AortaP, aortic blood pressure; Z, intracardiac impedance; vertical lines 100 msec in front of QRS complex. The respiratory influence is clearly visible in the pressure and impedance tracings. (From Bocchiardo M, Meyer zu Vilsendorf D, Militello C, et al: Intracardiac impedance monitors stroke volume in resynchronization therapy patients. Europace 12:702-707, 2010.)

ECG (mV)

An acute study of BiV impedance in 14 heart failure patients during implantation of a CRT device also tested the effect of different LV lead locations on BiV impedance measurements; changes in stroke

169

Applicability Clinical evaluations

Intrathoracic Impedance Pulmonary edema RV lead or coil to casing (tripolar) Takes about 1 month Yes Less Yes About 70% (depends on threshold) Pacemakers and ICD Relatively extensive

Biventricular Impedance LV volume RV-LV bipoles (quadripolar) Less Less Likely significant Yes N/A CRT-P or CRT-D Limited

CRT, cardiac resynchronization therapy; D, defibrillation ; ICD, implantable cardioverterdefibrillator; LV, Left ventricular; N/A, not available; P, pacing; RV, right ventricular.

volume were induced with overdrive pacing115 (Fig. 5-33). Data from 20 overdrive pacing episodes and six lead locations showed good correlation between measured stroke impedance and stroke volume (r = 0.82 ± 0.10) and pulse pressure (r = 0.81 ± 0.16). The authors reported no significant effect of LV lead positions on the efficacy of impedance measurement, although accuracy and signal size tended to be better in the midventricular region than in either the basal or the apical region. Lack of lead fixation was suggested for the one outlier in the study. At present, limited data are available on long-term outcome of these devices. Table 5-9 summarizes the relative merits and limitations of intrathoracic and biventricular (intracardiac) impedance. In patients with a suitable device (i.e., LV lead), combined transthoracic and BiV impedance likely can be used. MINUTE VENTILATION Because heart failure leads to compensatory hyperventilation (especially in the resting state), an expert system has been tested that combines activity and MV to predict heart failure.116 The algorithm includes (1) mean daily resting MV and MV during activity and (2) mean daily activity level. A stable MV and activity level will suggest stable clinical heart failure, whereas an increase in MV, especially at rest and combined with decrease in activity, suggests deteriorating heart failure. Conversely, a stable MV level with increase in activity indicates recovery from heart failure. A total of 19 patients with no heart failure history who had received a Talent DDDR (Sorin-ELA) were compared with 48 heart failure patients with a Talent CRT pacemaker. While mean activity was similar, the resting and activity MV levels were

1 0.5 0 –0.5 120 100 80 60 0.8 0.6 0.4 0.2 0 580

585

590

595 Time (s)

600

605

170

SECTION 1  Basic Principles of Device Therapy

higher in the CRT group. Overall, the expert system resulted in a sensitivity of 88%, specificity of 94.7%, positive predictive value of 71%, and negative predictive value of 98.2% for heart failure detection. ST-SEGMENT SHIFT An ST-segment deviation either heralds ischemia or myocardial injury. Myocardial ischemia requires medical therapy or revascularization, especially in symptomatic individuals. Myocardial injury, on the other hand, calls for medical emergency reperfusion. Prompt treatment of a myocardial infarction (MI) will significantly reduce mortality. Delay in patient recognition of MI-induced chest pain (or “silent” MI) contributes significantly to delayed MI presentation.117 Because long-term external ambulatory electrocardiographic recording is unlikely to be practical, electrograms have been proposed to reflect infarct and ischemia in an animal model.118 Incorporation into a CIED with patient alert and remote monitoring allows ST-segment monitoring. The Angel Med Guardian (now under St. Jude Medical) is a singlechamber device with an RV apical lead. An intracardiac electrogram (EGM) was derived from RV apex to the device casing. The device records 10 seconds of EGM data once every 90 seconds for normal sinus beat within 50 to 90 bpm. Data are amplified with a gain of 62.5 to 625 times and band-passed between 0.25 to 45 Hz, followed by A/D conversion at 200 Hz. ST-segment level is compared to the corresponding PQ-segment level, and a baseline ST level is calculated as a rolling 24-hour average, acquired hourly. The extent of the deviation is normalized by the average R-wave voltage. The “normalcy” of ST-segment deviation at different heart rates is further tested during an exercise test, because some ST shifts tend to occur at different heart rates in the absence of ischemia. A rate-adjusted spontaneous ST deviation then will be considered an ischemic event and an alert triggered. A limited number of Guardian devices have been implanted in humans.119 During angioplasty with temporary coronary artery occlusion, ST-segment deviations occurred, with a negative shift during left anterior descending artery occlusion and a positive shift in other arteries (Fig. 5-34). Ten abnormal alerts occurred in six patients, leading to coronary artery interventions. During stress testing, the EGM showed a much cleaner signal and greater shift than the corresponding surface ECG. Typically, a 40% ST depression in the EGM corresponds to −0.8

mV on the surface ECG. Because the EGM is recorded at the RV apex close to left anterior descending artery territory, ischemia in this artery leads to ST depression, whereas ischemia in other territories results in a reciprocal ST elevation. Further work is required to explore the ST-segment sensor’s ability to detect the problem artery. PEAK ENDOCARDIAL ACCELERATION The PEA sensor has been used for rate adaptation. The PEA signal measures the closure sound of the mitral valve and reflects cardiac contractility. A minimal PEA signal occurs during optimal A-V interval in DDD devices120 and reflects the optimal A-V interval in most patients. A new CRT-P (New Living CHF, Sorin) is now available to monitor heart function and to program A-V interval in CRT device. Both contractility and LV filling contribute to PEA, and an index known as “PEA area” is derived from the PEA values at different A-V and V-V intervals. The maximum PEA area will define the optimal V-V and A-V interval for the patient. In 15 patients implanted with CRT with PEA sensor, cardiac catheterization with LV dP/dt was measured with PEA area determined.35 A-V interval was scanned between 60 and 220 msec. The authors found a responder rate to CRT (defined as 10% increase in dP/dt) in 75% of patients. Concordance of PEA area versus dP/dt methods occurred in 8 of 12 patients. These data are interesting, although the role of PEA for A-V interval programming in the long term is uncertain, and the ability of the sensor to monitor LV function remains to be tested.

Combined Heart Failure Diagnostics The Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure (PARTNERS HF) is an observational study on the use of diagnostics to predict heart failure.121 A total of 100 U.S. sites prospectively recruited 694 CRT-D patients and followed them for 11.7 ± 2 months. Table 5-10 shows the diagnostic data considered important in an algorithm to predict ADHF. A positive algorithm was defined as the occurrence of 22 events in eight variables during a 1-month period, including long duration of atrial fibrillation (AF), rapid AF rate, increased OptiVol fluid index,

Baseline LAD

*

Inflation

Baseline LCX Inflation

Baseline RCA Inflation

0

5 Time in seconds

10

Figure 5-34  Guardian device recordings. Before (baseline) and 2 to 3 minutes after (inflation) balloon inflation, which occurred during angioplasty. Data are shown from three patients who underwent balloon occlusions of the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), resulting in ST-interval shifts of −42%, 34%, and 18%, respectively. In the LAD occlusion recording, the arrow points to the time at which the balloon was deflated. The negative ST shift begins to shift positive, toward the shape it demonstrated during the preocclusion baseline recording, within 2 beats. (From Hopenfeld B, John MS, Fischell DR, et al: The Guardian: an implantable system for chronic ambulatory monitoring of acute myocardial infarction. J Electrocardiol 42:481-486, 2009.)



171

5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

TABLE

Eight Cardiac Compass Heart Failure Device Diagnostic Parameters and Algorithms Used in PARTNERS Heart Failure Study

5-10 

Diagnostic Parameter Atrial fibrillation (AF) duration Ventricular rate during AF Fluid index (OptiVol) Patient activity Night heart rate Heart rate variability (HRV) Percentage of pacing CRT ICD shock for potentially lethal VT/VF

Algorithm AF ≥6 hours on at least 1 day in patients without persistent AF (7 consecutive days with ≥23 hours of AF) AF = 24 hours and average ventricular rate during AF ≥90 bpm on at least 1 day High fluid index on at least 1 day; thresholds included ≥60, ≥80, and ≥100 Ω/day Average patient activity 85 bpm for 7 consecutive days (nonoverlapping weekly windows) HRV 2 diagnostic criteria met % triggered evaluations (N = 1324)

6% P 2 diagnostic criteria met (N = 980)

Monthly evaluations with subsequent heart failure hospitalization (pulmonary)

low patient activity, abnormal autonomic tone, and device therapy. A very high OptiVol fluid level (>100 Ω/day) alone is considered positive diagnosis of ADHF. In PARTNERS heart failure, 90 patients had 141 adjudicated heart failure events, occurring 60 days after implantation. A positive combined diagnostic set predicts a 5.5-fold increased risk of hospitalization in the next month, even after adjusting for the clinical variables (Fig. 5-35). Figure 5-36 shows the main diagnostic parameters are OptiVol level of 60 Ω/day or greater, low activity, and heart rate variability (HRV). Additional OptiVol (≥100 Ω/day; 28% of patients) is also predictive of ADHF. Further subgroup analysis suggests that the specificity of ADHF improves with a higher fluid index and using more nonfluid-related indices at the expense of lower specificity. Interestingly, in patients with a prior heart failure history, diagnostic parameters are no longer predictive. The reason for this post-hoc analysis is uncertain. Diagnostic accuracy improves if sampling is performed every 15 days versus less often (Fig. 5-37).

10

20

30

Days after diagnostic evaluation Figure 5-35  Kaplan-Meier estimates of heart failure risk. Percentage of monthly evaluations with a subsequent heart failure hospitalization caused by signs or symptoms of pulmonary congestion. Patients with a positive combined heart failure device diagnostic algorithm had a 5.5-fold increased risk of a subsequent heart failure event within 30 days. CI, Confidence interval. (From Whellan DJ, Ousdigian KT, Al-Khatib SM, et  al; PARTNERS Study Investigators: Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS Heart Failure (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure) study. J Am Coll Cardiol 55:1803-1810, 2010.)

29%

28%

N = 980 evaluations 80

67%

60

62% 43%

40 20

21% 7%

14%

18% 5%

0 AF

0 0

43%

OptiVol >100 met

AF

AF OptiVol Low High Low Low ICD + >60 activity night HRV pacing shock(s) heart % RVR rate Fluid Activity Autonomics Device Therapy

Figure 5-36  Combined heart failure device diagnostics triggered. Venn diagram shows that 72% of evaluations had two or more (≥2) heart failure device diagnostics triggered, with the remaining 28% triggered by OptiVol fluid index of ≥100 Ω/day. OptiVol fluid index, low activity, and low heart rate variability (HRV) were the most common reasons for triggers. AF, Atrial fibrillation; ICD, implantable cardioverter-defibrillator; RVR, rapid ventricular response. (From Whellan DJ, Ousdigian KT, Al-Khatib SM, et al; PARTNERS Study Investigators: Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS Heart Failure (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure) study. J Am Coll Cardiol 55:1803-1810, 2010.)

172

SECTION 1  Basic Principles of Device Therapy

Algorithms

P-value 2.7

Fluid index >60

80

100

70 years).88 Of 952 patients with a first pacemaker implantation between 1994 and 1999, 755 were excluded from the study, mainly for AV block (48%), permanent AF (10%), or BBB (5%), and only 2% of patients did not give consent. The 177 enrolled patients were randomized to receive an AAIR pacing system (n = 54) or a DDDR system programmed to a short AV delay

Study

Physiologic

Ventricular

Wt%

HR [95% CI]

Danish

26/110

40/115

4.5

0.54 [0.33,0.89]

CTOPP

224/1094

367/1474

40.3

0.8 [0.68,0.95]

PASE

35/203

38/204

5.3

0.91 [0.57,1.44]

MOST

217/1014

270/996

34.9

0.79 [0.66,0.94]

UKPACE

98/1012

111/1009

15.1

0.88 [0.67,1.16]

Overall

600/3433

826/3798

100

0.8 [0.72,0.89]

Homogeneity: chi-square = 3.26 df = 4 p = 0.52 Association: chi-square = 17.43 p = 3e–05 0.25

0.50

1.00

2.00

Hazard ratio Figure 10-5  Pooled estimate of atrial fibrillation in randomized trials of pacing mode.



10  Clinical Trials of Atrial and Ventricular Pacing Modes

Study

Physiologic

Ventricular

Wt%

HR [95% CI]

105/1094

156/1474

34.5

0.9 [0.7,1.15]

PASE

14/203

24/204

4.9

0.55 [0.28,1.06]

MOST

104/1014

123/996

31

0.82 [0.63,1.06]

UKPACE

111/1012

105/1009

29.7

1.04 [0.8,1.36]

Overall

334/3323

408/3683

100

0.89 [0.77,1.03]

CTOPP

245

Homogeneity: chi-square = 3.76 df = 3 p = 0.29 Association: chi-square = 2.46 p = 0.12 0.25

0.50

1.00

2.00

Hazard ratio Figure 10-6  Pooled estimate of hospitalization for heart failure in randomized trials of pacing mode.

(150 msec, DDDR-s, n = 60) or a long AV delay (300 msec, DDDR-l, n = 63). Echocardiographic (left atrial diameter, left ventricular function and size) and clinical (AF, stroke or arterial embolism, mortality, heart failure) outcomes were assessed in these three modes of pacing in SND. During the study, patients in the DDDR-s group received pacing for a mean of 90%. Patients in the DDDR-l group still received 17% of (a priori unnecessary) ventricular pacing. After a mean follow-up of 3 years, patients randomized to AAIR did not show a significant change in left atrial diameter, left ventricular diameter or LVEF shortening compared to baseline. In contrast, left atrial diameter was increased and left ventricular shortening fraction decreased significantly in the DDDR-s patients. In the DDDR-l group, the left atrial diameter and the left ventricular end-systolic and end-diastolic diameters increased significantly during the 3-year follow-up. Atrial fibrillation in the 12-lead ECG during at least one follow-up visit was significantly less common in AAIR (7.4%) than in DDDR-s (23.3%) or DDDR-l (17.5%).89 During the study, 16 strokes occurred in 14 patients, but no peripheral embolism was observed. Clinical events, including all-cause mortality, cardiovascular mortality, development of CHF, and increased use of diuretics, did not differ among the three groups. However, progression of HF symptoms, although not significantly different among the groups, was seen, with an increase of at least one NYHA class in 31% of patients paced in AAIR mode versus 30% in DDDR-s and 46% in DDDR-l. The study by Nielsen et al.87 would have required 450 patients for an 80% power to detect clinical or echocardiographic differences between AAIR and DDDR (no differences between DDDR-s and DDDR-l were expected). Inclusion was stopped when a multicenter trial (DANPACE) randomizing SND patients to AAIR versus DDDR pacing was initiated. However, the results of this study from Aarhus suggest that in patients with SND, narrow QRS and normal AV conduction dual-chamber pacing compared to AAIR pacing may result in deleterious effects in terms of left atrial enlargement, left ventricular volumes and ejection fraction, and AF incidence. Surprisingly, even in these select patients, programming the AV delay to very long values was unable to prevent a significant proportion of unnecessary right ventricular pacing. The observed proportion of ventricular pacing of 17% had detrimental effects in terms of left atrial dilatation and incidence of AF similar to DDDR pacing with short AV delay. In a study following these observations, Albertsen et al.90 randomized 50 patients with sinus node disease to AAIR or DDDR (AV delay 220 msec paced and 200 msec sensed). Primary endpoint was dyssynchrony (evaluated by tissue-Doppler imaging with at least 1 segment

with delayed longitudinal contraction) and LVEF (evaluated by 3D echocardiography) after 12 months compared to baseline. Physicians performing echocardiography were blinded with regard to pacing mode. Secondary endpoints referred to 6-minute walking test and NT-proBNP. During follow-up, patients with DDDR pacing received ventricular pacing for 66% of the time. Dyssynchrony slightly increased with DDDR pacing (mean of 1.3 delayed segments at baseline vs. 2.1 after 12 months) but not in AAIR pacing. Although LVEF decreased statistically significant with DDDR pacing (63% at baseline vs. 59% after 12 months; no change observed in AAIR pacing), there was no difference between AAIR and DDDR pacing after 12 months in NYHA class or NT-proBNP. These results confirm other observations of deteriorated left ventricular function with unnecessary right ventricular pacing, and suggest the development of left ventricular dyssynchrony as one cause. At the same time, echocardiographic changes from baseline did not translate into significant clinical changes in this small study. The Danish multicenter randomized trial on single-lead atrial versus dual-chamber pacing in patients with sick sinus syndrome (DANPACE) was started in 1999.91 It compared AAIR and DDDR pacing in patients with SND but with no BBB or AV block (except for PR interval ≤220 msec for patients 3 mo) NYHA I-III, EF ≤ 0.35, dilated cardiomyopathy NSVT, or ≥10 PVCs/hr

ICD vs. best medical therapy

All-cause mortality

No significant alteration (P = .6) with ICD

Resynchronization ICD vs. best medical therapy

All-cause death or hospitalization

20% relative reduction in primary endpoint (P = .01) with resynchronization ICD

ICD vs. placebo

All-cause mortality

ICD vs. best medical therapy

All-cause mortality

23% relative reduction in primary endpoint (P < .01) with ICD 35% relative reduction in primary endpoint (P = .08) with ICD

CABG, Coronary artery bypass graft surgery; EF, ejection fraction; MI, myocardial infarction; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association functional class; PVCs, premature ventricular complexes.



11  Clinical Trials of Defibrillator Therapy

TABLE

11-4 

265

Clinical Trials of ICD Therapy for Heart Failure or Left Ventricular Dysfunction Alone: Population Details and Mortality Results Mortality Results: ICD vs. Other (%)

Trial MADIT-II (2002) AMIOVIRT (2003) CAT (2002) COMPANION* (2004) SCD-HeFT* (2005) DEFINITE (2005)

N 1232 103 104 903 1676 458

Age (yr) 64 52 52 67 60 58

Women (%) 16 30 20 32 23 29

NYHA >II (%) 29 20 35 100 30 21

Mean Ejection Fraction 0.23 0.23 0.24 0.22 0.25 0.21

Mean Followup (mo) 20 24 23 15 46 29

Annual Relative Rate in Controls 10 4 4 19 7 7

Relative Risk Reduction 31 13 17 36 23 35

Absolute Risk Reduction 5.4 1.7 5.4 7.3 6.8 5.2

Number Needed to Treat (36 mo) 10 39 12 5 23 24

NYHA, New York Heart Association functional class. *Patient numbers reflect assignment to an ICD or medical therapy (COMPANION)/placebo (SCD-HeFT).

European centers from July 1997 to January 2002.56 ICD therapy was compared with usual care in patients with ischemic LV dysfunction (LVEF ≤0.30). Patients who had experienced a recent MI (within 1 month of evaluation) or revascularization procedure (within 3 months of evaluation) were not eligible. Patients who underwent invasive electrophysiologic testing and had inducible sustained arrhythmias, fulfilling the criteria for MADIT-I, were also ineligible.Angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and lipid-lowering therapies were prescribed to 70%, 70%, and 66% of participants, respectively, on the basis of data from the last follow-up visit. These rates are higher than in the trials evaluating ICD efficacy in patients with spontaneous or inducible ventricular arrhythmias conducted before the wider recognition of the importance of these medications. Patients were followed up for an average of 20 months. ICD therapy was associated with a 31% relative reduction in mortality (95% CI = 7% to 49%; P 120 msec) had larger absolute and relative risk reductions that trended toward statistical significance. Some considered this finding to indicate that patients with QRS values greater than 120 msec benefit from ICD therapy and that those with shorter QRS values do not, but this remains controversial.111 Delayed ventricular conduction has also been shown to predict a higher risk of death among patients receiving contemporary medical therapy.80 Other noninvasive risk assessment tools, such as T-wave alternans, have been advocated for selecting patients for ICD therapy,112 but their usefulness remains unproved83 (see Ongoing Trials).

The ability of electrophysiologic testing to predict mortality and ICD efficacy was also assessed in MADIT-II.68,113 Electrophysiologic inducibility was performed on 593 patients randomly assigned to ICD therapy. A sustained ventricular arrhythmia was inducible in 36% of patients, who were more likely to demonstrate spontaneous VT in follow-up. In contrast, patients who did not have a sustained inducible ventricular arrhythmia were more likely to experience spontaneous VF. Overall, patients in MADIT-II had a 20% rate of appropriate ICD therapies for VT or VF over 4 years of follow-up. The likelihood of VT or VF was similar for patients with and without inducible arrhythmias at baseline. As with the findings in MUSTT, the MADIT-II data indicate that electrophysiologic testing is suboptimal in identifying patients who will benefit from an ICD. Analyses from MADIT-II include clinical risk factors associated with benefit from ICD therapy114 and with mortality in ICD recipients115 and utility of noninvasive tests to predict ICD benefit. Although both dynamic alterations in QT duration116 and morphology117 predicted an increased risk of death and arrhythmias in MADIT-II, neither measure was useful in discriminating between patients likely versus unlikely to benefit from an ICD. A risk score comprised of five clinical factors (NYHA Class >II, age >70, BUN >26 mg/dL, QRS duration >120 msec, atrial fibrillation) was derived after excluding patients with blood urea nitrogen (BUN) values of at least 50 mg/dL and/or serum creatinine values of at least 2.5 mg/dL. Conventional therapy patients with none of these risk factors had an 8% mortality rate, and those with at least one risk factor had a 28% mortality rate. ICD therapy was not associated with a significant alteration in mortality among the 345 patients with no risk factors (hazard ratio 0.96; P = .91), but was associated with a 49% relative reduction in the risk of death in the 786 patients with at least one risk factor (P 200 pg/mL

Comparison ICD vs. usual care (1 : 1)

N 1550

Primary Endpoint Mortality

Identifier NCT00487279

Status Enrolling

Wearable AED vs. usual care (1 : 1) ICD vs. usual care (1 : 1)

2400

NCT00628966

Enrolling

1400

Sudden death mortality Mortality

NCT00673842

Enrolling

ICD vs. usual care (1 : 1)

1000

Mortality

NCT00541268 NCT00542945

Enrolling

AED, Automated external defibrillator; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MRI, magnetic resonance imaging; NT-BNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association functional class.

tolerated. The primary outcome is time to death from any cause. It is expected to require 2 years of enrollment, with at least 36 months of follow-up. Other Trials Other randomized trials (not listed) are assessing the safety and efficacy of methods to reduce the likelihood of ICD shocks, the utility of CRT in patient groups in whom there is insufficient evidence to date (e.g., narrow QRS duration), and the value of remote monitoring of implanted devices. Several other observational studies assessing risk prediction tools (Holter, imaging, genetic) are also ongoing.

Other Issues COST-EFFECTIVE, NOT INEXPENSIVE Regardless of a clinician’s philosophy related to costly interventions, a fundamental principle is that the choice to implant an ICD must be based on a reasonable probability of success. This principle must be considered in terms of a broad perspective (mortality, QOL, potential complications, cost). Although therapies are labeled as “cost-effective” if they are similar in cost to other interventions (e.g., renal dialysis), this label does not mean that they are “inexpensive.” This issue is of particular relevance when a physician concurrently uses multiple interventions in a single patient (e.g., renal dialysis, CABG, ICD). Ultimately, because of the evolving face of health care delivery, issues of cost influence the practice of medicine. It is also paramount to appreciate that estimates of cost-effectiveness derived from clinical trials may not mirror “real-world” costs. IS THERE A NEED FOR ADDITIONAL RISK ASSESSMENT? Controversy surrounds the use of ICD therapy in all patients with an LVEF of 0.35 or less.177,178 Although widespread use of ICD therapy for prevention of arrhythmic death is understandable, this approach still carries the risk of complications related to implantation and subsequent revisions, besides the cost. Although extrapolation of the findings of past studies is reasonable and often necessary, it is prudent to consider a reasonable probability of success, including assessment of sudden death risk versus the risk of competing modes of death. The analyses from CIDS,103 MUSTT,109 and MADIT-II114 indicate that patients with significant comorbidity, particularly chronic renal impairment,179 may benefit from ICD therapy to a lesser extent. Other sources of data, including large registries, may aid in better selection of appropriate candidates for ICD therapy (see Real-World Effectiveness). In an attempt to include a greater proportion of patients at risk for sudden death (see Fig. 11-2), LV dysfunction has been a major inclusion criterion for most of the completed ICD trials (see Table 11-3).

However, many of these patients do not experience life-threatening arrhythmias in the near term. The incidence of appropriate ICD therapies ranges from 28% to 68% over the initial 2 to 5 years after ICD implantation, depending on the population studied and the duration of follow-up.151,154,180 Patients receiving an ICD on the basis of heart failure or LV dysfunction alone have a twofold to threefold lower risk of life-threatening arrhythmias in the initial 2 to 5 years of follow-up than patients with a history of spontaneous sustained VT/VF181-183 or inducible sustained VT/VF.184 Identifying higher-risk groups in those receiving an ICD for heart failure or LV dysfunction alone has been undertaken.103,109,114 Although useful in helping physicians better understand which patients may benefit from an ICD, these clinical scores should be used as “hypothesis-generating” tools, given the lack of prospective validation to date. Although the relative efficacy of an ICD is similar in most of the ICD trials (see Fig. 11-4), the absolute effect differs substantially. Among sudden death survivors22 and patients with ischemic LV dysfunction and inducible arrhythmias,64,91 the average absolute risk reduction was about 12%. Therefore, the NNT for ICD therapy in this group is approximately 8. In contrast, among patients with only LV dysfunction,23,133 the average absolute benefit was about 6%, translating into an NNT of 16. These data have been used to support the need for methods to better identify patients in whom ICD therapy leads to a greater absolute risk reduction and a lower NNT. The long-term data from MADIT-II identify a large, 13% absolute reduction in mortality with ICD therapy in patients with LV dysfunction.50 This reduction in mortality is similar to that in the randomized trials of ICD therapy in secondary prevention patients, although over shorter follow-up (see Fig. 11-4). The results of RAFT provide further evidence of the cost effectiveness of adding CRT to ICD therapy in patients with prolonged QRS durations and symptomatic heart failure (see Other Informative ICD Trials). Given the consequence of sudden death, it is imperative that a balance is reached between identifying patients with a significant absolute mortality reduction with ICD therapy (specificity) but not excluding most who will die from sudden death (sensitivity) (see Fig. 11-3). Noninvasive tools have also been advocated to better identify patients likely versus unlikely to benefit from an ICD. As discussed, these methods have not proved useful in guiding ICD therapy to date. Ongoing trials (e.g., DETERMINE, REFINE ICD) are assessing whether these tools can be used to select patients in whom an ICD will reduce mortality. Until these and other trials have been completed, it is unclear what role, if any, these methods have in guiding ICD therapy. REAL-WORLD EFFECTIVENESS The sites participating in the reviewed randomized trials are typically high-volume, academically oriented centers. The success rates and complication rates achieved in these trials may not reflect the

276

SECTION 2  Clinical Concepts

results in other centers. Until recently, little was known about the real-world success rates and complications of ICD placement. This issue is particularly relevant when the results of more complex ICD systems that include CRT are applied to less experienced centers, given the steep learning curve associated with implantation of LV leads.185 Large registries have been initiated to assess real-world effectiveness of ICD therapy, most notably the U.S. National Cardiovascular Data Registry (NCDR) Registry. Insights from the NCDR and other registries include improved outcomes when devices are implanted by electrophysiologists versus non-electrophysiologists,186 better outcomes in higher-volume than lower-volume implant centers,187 and significantly impaired outcomes in ICD recipients from comorbidities such as chronic renal disease.188 These data complement the findings from randomized trials. Registry data have also provided insight into implant complications, showing a twofold higher rate of complications with dual-chamber and CRT systems versus single-chamber ICD systems.189 Registry data have also helped in identifying barriers related to device implantation190,191 and the off-label use of devices.53,54 Despite limitations, registry data are providing important insights into real-world application of ICD systems.

Conclusion With advances in implantable cardioverter-defibrillator technology, the patient populations who may benefit from ICD therapy continue to expand. Many trials evaluating ICD efficacy in a variety of settings have convincingly demonstrated that the ICD is superior to antiarrhythmic drug therapy in patients with spontaneous or inducible ventricular arrhythmias. Also, ICD therapy improves the survival of patients with heart failure or LV dysfunction caused by ischemic heart disease or dilated cardiomyopathy. However, patients with LV dysfunction in specific circumstances, notably those with recent myocardial infarction, do not appear to benefit from ICD therapy. Ongoing and future studies will address the role of the ICD early after MI, as well as which patients benefit most from ICD therapy. Issues of reliability, cost, quality of life, and real-world outcomes will also feature prominently in future studies. A tremendous debt of gratitude is owed to the thousands of patients who have helped us learn so much about the usefulness and limitations of ICD therapy over the past 25 years. Without the time and effort of these individuals, we would know far less, and our capacity to reduce the burden of sudden death and improve the lives of so many individuals would be greatly diminished.

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J Am Coll Cardiol 47:1820-1827, 2006. 128. Blatt JA, Poole JE, Johnson GW, et al: No benefit from defibrillation threshold testing in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). J Am Coll Cardiol 52:551-556, 2008. 129. Healey JS, Birnie DH, Lee DS, et al: Defibrillation Testing at the Time of ICD Insertion: An Analysis from the Ontario ICD Registry. J Cardiovasc Electrophysiol 21:1344-1348, 2010. 130. Kadish A, Dyer A, Daubert JP, et al: Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 350:2151-2158, 2004. 131. Ellenbogen KA, Levine JH, Berger RD, et al: Are implantable cardioverter defibrillator shocks a surrogate for sudden cardiac death in patients with nonischemic cardiomyopathy? Circulation 113:776-782, 2006. 132. Kadish A, Schaechter A, Subacius H, et al: Patients with recently diagnosed nonischemic cardiomyopathy benefit from implantable cardioverter-defibrillators. J Am Coll Cardiol 47:2477-2482, 2006. 133. Nanthakumar K, Epstein AE, Kay GN, et al: Prophylactic implantable cardioverter-defibrillator therapy in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials. J Am Coll Cardiol 44:2166-2172, 2004. 134. Bigger JT, Jr, Whang W, Rottman JN, et al: Mechanisms of death in the CABG Patch trial: a randomized trial of implantable cardiac defibrillator prophylaxis in patients at high risk of death after coronary artery bypass graft surgery. Circulation 99:14161421, 1999. 135. Bailey JJ, Berson AS, Handelsman H, Hodges M: Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction. J Am Coll Cardiol 38:19021911, 2001. 136. Bauer A, Guzik P, Barthel P, et al: Reduced prognostic power of ventricular late potentials in post-infarction patients of the reperfusion era. Eur Heart J 26:755-761, 2005. 137. Al-Khatib SM, Hellkamp AS, Lee KL, et al: Implantable cardioverter defibrillator therapy in patients with prior coronary revascularization in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). J Cardiovasc Electrophysiol 19:1059-1065, 2008. 138. Barsheshet A, Goldenberg I, Narins CR, et al: Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT. Heart Rhythm 7:1421-1427, 2010. 139. Dorian P, Connolly S, Hohnloser SH: Why don’t ICDs decrease all-cause mortality after MI? Insights from the DINAMIT study. Circulation 110:502, 2004. 140. Savoye C, Equine O, Tricot O, et al: Left ventricular remodeling after anterior wall acute myocardial infarction in modern clinical practice (from the REmodelage VEntriculaire [REVE] study group). Am J Cardiol 98:1144-1149, 2006. 141. Huikuri HV, Exner DV, Kavanagh KM, et al: Attenuated recovery of heart rate turbulence early after myocardial infarction identifies patients at high risk for fatal or near-fatal arrhythmic events. Heart Rhythm 7:229-235, 2010. 142. Nolan J, Batin PD, Andrews R, et al: Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom Heart Failure Evaluation and Assessment of Risk Trial (UK-Heart). Circulation 98:1510-1516, 1998. 143. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 51:e1-e62, 2008. 144. Fogoros RN: An AVID dissent (editorial) [see comments]. Pacing Clin Electrophysiol 17:1707-1711, 1994. 145. Epstein AE: AVID necessity. Pacing Clin Electrophysiol 16:17731775, 1993. 146. Maron BJ, Shen WK, Link MS, et al: Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy [see comments]. N Engl J Med 342:365-373, 2000.

147. Piccini JP, Dalal D, Roguin A, et al: Predictors of appropriate implantable defibrillator therapies in patients with arrhythmogenic right ventricular dysplasia. Heart Rhythm 2:1188-1194, 2005. 148. Maron BJ, Spirito P, Shen WK, et al: Implantable cardioverterdefibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 298:405-412, 2007. 149. Costantini O, Hohnloser SH, Kirk MM, et al: The ABCD (Alternans Before Cardioverter Defibrillator) Trial: strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention. J Am Coll Cardiol 53:471-479, 2009. 150. Chow T, Kereiakes DJ, Bartone C, et al: Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy. J Am Coll Cardiol 49:50-58, 2007. 151. Klein RC, Raitt MH, Wilkoff BL, et al: Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics versus Implantable Defibrillators (AVID) Trial. J Cardiovasc Electrophysiol 14:940-948, 2003. 152. Wathen M: Implantable cardioverter defibrillator shock reduction using new antitachycardia pacing therapies. Am Heart J 153:44-52, 2007. 153. Grimm W, Flores BT, Marchlinski FE: Shock occurrence and survival in 241 patients with implantable cardioverterdefibrillator therapy. Circulation 87:1880-1888, 1993. 154. Grimm W, Hoffmann JJ, Muller HH, Maisch B: Implantable defibrillator event rates in patients with idiopathic dilated cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left ventricular ejection fraction below 30%. J Am Coll Cardiol 39:780-787, 2002. 155. Garratt CJ, Elliott P, Behr E, et al: Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes. Europace 12:1156-1175, 2010. 156. Maron BJ, Olivotto I, Spirito P, et al: Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large nonreferral-based patient population. Circulation 102:858-864, 2000. 157. Maron BJ, Casey SA, Hauser RG, Aeppli DM: Clinical course of hypertrophic cardiomyopathy with survival to advanced age. J Am Coll Cardiol 42:882-888, 2003. 158. Elliott P, Gimeno J, Mahon N, et al: Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 357:420-424, 2001. 159. Maron BJ, Thompson PD, Ackerman MJ, et al: Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 115:1643-1655, 2007. 160. O’Hanlon R, Grasso A, Roughton M, et al: Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 56:867-874, 2010. 161. Bruder O, Wagner A, Jensen CJ, et al: Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 56:875-887, 2010. 162. Gosling OE, Bellenger N, Spurrell P: Risk assessment with cardiac magnetic resonance imaging in hypertrophic cardiomyopathy. Heart 95:1843, 2009. 163. Pierre-Louis B, Prasad A, Frishman WH: Cardiac manifestations of sarcoidosis and therapeutic options. Cardiol Rev 17:153-158, 2009. 164. Syed J, Myers R: Sarcoid heart disease. Can J Cardiol 20:89-93, 2004. 165. Kim JS, Judson MA, Donnino R, et al: Cardiac sarcoidosis. Am Heart J 157:9-21, 2009. 166. Aizer A, Stern EH, Gomes JA, et al: Usefulness of programmed ventricular stimulation in predicting future arrhythmic events in patients with cardiac sarcoidosis. Am J Cardiol 96:276-282, 2005. 167. Patel MR, Cawley PJ, Heitner JF, et al: Detection of myocardial damage in patients with sarcoidosis. Circulation 120:1969-1977, 2009. 168. Marcus FI, McKenna WJ, Sherrill D, et al: Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 121:15331541, 2010. 169. Dalal D, Nasir K, Bomma C, et al: Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation 112:3823-3832, 2005. 170. Corrado D, Leoni L, Link MS, et al: Implantable cardioverterdefibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/ dysplasia. Circulation 108:3084-3091, 2003. 170a.  Olshansky B, Day JD, Moore S, et al: Is dual-chamber programming inferior to single chamber programming in an implantable cardioverter-defibrillator? Results of the INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AVSH in ICDs) study. Circulation 115:9-16, 2007.

171. Wilkoff BL, Kudenchuk PJ, Buxton AE, et al: The DAVID (Dual Chamber and VVI Implantable Defibrillator) II trial. J Am Coll Cardiol 53:872-880, 2009. 172. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115-3123, 2002. 173. Moss AJ, Hall WJ, Cannom DS, et al: Cardiac-resynchronization therapy for the prevention of heart failure events. N Engl J Med 361:1329-1338, 2009. 174. Solomon SD, Foster E, Bourgoun M, et al: Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: Multicenter Automatic Defibrillator Implantation Trial: cardiac resynchronization therapy. Circulation 122:985992, 2010. 175. Dickstein K, Vardas PE, Auricchio A, et al: 2010 focused update of ESC Guidelines on Device Therapy in Heart Failure: an update of the 2008 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure and the 2007 ESC Guidelines for Cardiac Resynchronization Therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur Heart J 31:2677-2687, 2010. 176. Tang AS, Wells GA, Talajic M, et al: Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators; Cardiac resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363:2385-2395, 2010. 177. Moss AJ: Should everyone with an ejection fraction less than or equal to 30% receive an implantable cardioverter-defibrillator? Everyone with an ejection fraction ≤30% should receive an implantable cardioverter-defibrillator. Circulation 111:25372549, discussion 2549, 2005. 178. Buxton AE: Should everyone with an ejection fraction less than or equal to 30% receive an implantable cardioverter-defibrillator? Not everyone with an ejection fraction ≤30% should receive an implantable cardioverter-defibrillator. Circulation 111:25372549, 2005. 179. Goldenberg I, Moss AJ: Implantable cardioverter defibrillator efficacy and chronic kidney disease: competing risks of arrhythmic and nonarrhythmic mortality. J Cardiovasc Electrophysiol 19:1281-1283, 2008. 180. Theuns DA, Klootwijk AP, Simoons ML, Jordaens LJ: Clinical variables predicting inappropriate use of implantable cardioverter-defibrillator in patients with coronary heart disease or nonischemic dilated cardiomyopathy. Am J Cardiol 95:271274, 2005. 181. Capoferri M, Schwick N, Tanner H, et al: Incidence of arrhythmic events in patients with implantable cardioverter-defibrillator for primary and secondary prevention of sudden cardiac death. Swiss Med Wkly 134:154-158, 2004. 182. Wilkoff BL, Hess M, Young J, Abraham WT: Differences in tachyarrhythmia detection and implantable cardioverter defibrillator therapy by primary or secondary prevention indication in cardiac resynchronization therapy patients. J Cardiovasc Electrophysiol 15:1002-1009, 2004. 183. Theuns DA, Thornton AS, Klootwijk AP, et al: Outcome in patients with an ICD incorporating cardiac resynchronisation therapy: differences between primary and secondary prophylaxis. Eur J Heart Fail 7:1027-1032, 2005. 184. Backenkohler U, Erdogan A, Steen-Mueller MK, et al: Long-term incidence of malignant ventricular arrhythmia and shock therapy in patients with primary defibrillator implantation does not differ from event rates in patients treated for survived cardiac arrest. J Cardiovasc Electrophysiol 16:478-482, 2005. 185. Kautzner J, Riedlbauchova L, Cihak R, et al: Technical aspects of implantation of LV lead for cardiac resynchronization therapy in chronic heart failure. Pacing Clin Electrophysiol 27:783-790, 2004. 186. Curtis JP, Luebbert JJ, Wang Y, et al: Association of physician certification and outcomes among patients receiving an implantable cardioverter-defibrillator. JAMA 301:1661-1670, 2009. 187. Freeman JV, Wang Y, Curtis JP, et al: The relation between hospital procedure volume and complications of cardioverterdefibrillator implantation from the Implantable CardioverterDefibrillator Registry. J Am Coll Cardiol 56:1133-1139, 2010. 188. Aggarwal A, Wang Y, Rumsfeld JS, et al: Clinical characteristics and in-hospital outcome of patients with end-stage renal disease on dialysis referred for implantable cardioverter-defibrillator implantation. Heart Rhythm 6:1565-1571, 2009. 189. Lee DS, Krahn AD, Healey JS, et al: Evaluation of early complications related to de novo cardioverter-defibrillator implantation: insights from the Ontario ICD database. J Am Coll Cardiol 55:774-782, 2010. 190. Daugherty SL, Peterson PN, Wang Y, et al: Use of implantable cardioverter-defibrillators for primary prevention in the community: do women and men equally meet trial enrollment criteria? Am Heart J 158:224-229, 2009. 191. Curtis AB, Yancy CW, Albert NM, et al: Cardiac resynchronization therapy utilization for heart failure: findings from IMPROVE HF. Am Heart J 158:956-964, 2009.

12  12

Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators SANDEEP TALWAR  |  LESLIE A. SAXON

A

paradigm shift in the treatment of heart failure from purely pharmacologic therapy to a strategy that now includes electrical therapy was heralded by the outcomes of major landmark trials of cardiac resynchronization therapy (CRT), which are reviewed in this chapter. These trials have elucidated the relative roles of pacing, defibrillation, and intraventricular conduction delay in the natural history of heart failure. They have helped to identify patient populations who benefit from device therapy as well as limitations in selecting patients based on measures other than QRS width (duration). Advances in remote device follow-up technology are further refining daily management and improving outcomes in heart failure patients. Treatment of the heart failure disease substrate with device-based therapy such as CRT has expanded the potential of a heart failure device that not only treats heart failure, but also diagnoses and prevents heart failure exacerbations and arrhythmic events, aiding overall patient management and tracking. Patients with advanced heart failure can receive contemporary medical therapy combined appropriately with electrical resynchronization. Also, their outcome may be predicted by powerful point-of-source data sets that allow for daily diagnostic measures and patient participation in disease management.1-10 Resynchronization devices now represent about 40% of all implantable cardioverter-defibrillators (ICDs) used in the United States.11 Review of clinical trial data shows that at least one third of patients for whom ICDs are indicated also qualify for a CRT with defibrillator (CRT-D) device.12,13 This proportion is likely to increase with expansion of CRT therapy to patients with mild to moderate heart failure.14 Although the implant procedure for a CRT-D is technically more challenging than that for an ICD, CRT has the added advantages of making patients feel better, causing reverse ventricular remodeling, and reducing heart failure hospitalizations—three important goals when offering device therapy to a population with heart failure.2,9,15,16 Despite the evidence base and guidelines, CRT is underutilized in eligible patients, with significant variation in age, gender, QRS duration, care provider, insurance status, and geographic location of practices.17 This chapter also reviews advances in lead technology, and device features for delivering CRT itself or expanding CRT, such as remote device follow-up and enhanced CRT–heart failure diagnostic devices.18-23

Heart Failure and QRS Delay: Scope of the Problem The greatest expense for the U.S. Medicare Trust Fund is the treatment of heart failure.24-28 The majority of this expense is in the acute management of heart failure hospitalizations, which often require intensive care unit management.26 There are not only about 1 million heart failure hospitalizations yearly, but also 300,000 heart failure deaths. These deaths are primarily caused by progressive pump dysfunction and sudden cardiac death, both of which can be addressed with a CRT and pacemaker (CRT-P) or CRT-D device.8,9 As heart failure severity

increases, characterized by both mechanical and electrical remodeling, the primary cause of cardiovascular death typically is pump failure. Conversely, as heart failure functional class improves, electrical instability plays a more prominent role, such that the absolute number of sudden deaths in the patient with advanced heart failure and QRS prolongation is significant, accounting for about one third of all deaths.29,30 When it accompanies heart failure from systolic dysfunction, QRS delay (≥120 msec) itself adds significant morbidity and mortality.31-36 In fact, mortality rates progressively increase as intraventricular conduction delay increases. The latter may also predispose heart failure patients to an increased risk of ventricular arrhythmias by acting as a substrate for reentrant ventricular tachycardia.37 Affecting 30% to 50% of patients with New York Heart Association (NYHA) Class III or IV heart failure, QRS delay, predominantly left bundle branch block (LBBB), impairs cardiac function by introducing intraventricular dyssynchrony. Severe mechanical left ventricular (LV) dyssynchrony is observed in 60% to 70% of patients with QRS duration of 120 msec or greater. It was previously thought that this group of patients with advanced heart failure would be most likely to benefit from resynchronization therapy; this chapter reviews data disproving this assumption. Conduction delay also worsens atrioventricular (AV) and interventricular (VV) dyssynchrony, whereas intraventricular dyssynchrony results in worsening LV function, as measured by the rise of left ventricular pressure (dP/dt) and filling times.38-41 Interestingly, even in patients with right bundle branch block (RBBB) or intraventricular conduction delay, significant electrical delay to the left ventricle is observed on detailed activation mapping, suggesting that RBBB in this setting often represents “concealed” LBBB.42,43

Studies of CRT in the Acute Setting: How Does It Work? Cardiac resynchronization therapy is defined as the stimulation of the left ventricle or simultaneous stimulation of both the right and the left ventricle after atrial sensed or paced events or in atrial fibrillation (AF). CRT works by multiple mechanisms, ranging from structural changes (e.g., favorable ventricular remodeling, improved peak oxygen consumption, reduced mitral regurgitation) to cellular and molecular changes (e.g., improved adrenergic-stimulated myocyte function, decreased neurohormonal activation, altered ionic currents and calcium homeostasis). In an elegant study, Tomaselli’s group recently demonstrated that CRT abbreviates the dyssynchronous heart failure–induced prolongation of action potential in cells isolated from the LV lateral wall. Aiba et al.44 conclude that CRT partially reverses the cellular triggers and substrate for arrhythmias in this pacing-induced model of heart failure. CRT works by partially or totally correcting AV, VV, and most importantly left intraventricular dyssynchronies, leading to reverse remodeling and restoring adverse electrophysiologic, neurohormonal, and anatomic changes that result from heart failure.40,44-50 The predominant beneficial effects are on measures of systolic function, as summarized in Table 12-1 and discussed in detail in Chapter 9.

279

280

TABLE

12-1 

SECTION 2  Clinical Concepts

Mechanisms of Acute Improvement in Cardiac Function with Cardiac Resynchronization Therapy (CRT)

Type of CRT Atrioventricular (AV) resynchronization Inter/intraventricular resynchronization

Mechanisms Diminished mitral regurgitation Lengthened diastolic filling time Optimization of filling pattern Increases in left ventricular efficiency/systolic blood pressure, dP/dt, pulse pressure, stroke volume, and stroke work Decrease in left ventricular end-systolic volume

In the first closed-chest study of CRT, in 27 subjects with heart failure and QRS delay, Blanc et al.45 demonstrated improvements in systolic blood pressure, pulmonary capillary wedge pressure, and V-wave amplitude with LV or biventricular (BiV) stimulation compared with baseline or right ventricular (RV) pacing. Kass et al.39 and Aurrichio et al.46 subsequently demonstrated that the effects of CRT could be further optimized by AV delay timing to achieve immediate increases in dP/dt and pulse pressure of 12% to 25% with LV or BiV stimulation, in a total of 45 patients. Figure 12-1 demonstrates the effects of pacing site on pressure-volume loops obtained in a patient with heart failure and LBBB. Neither RV pacing site alters the abnormal

loop. However, both left ventricular free wall (LVFW) and BiV stimulation result in reduced LV end-systolic volume and increased stroke volume and stroke work (increased loop width and area). These changes correlated with improved pulse pressure. Interestingly, in the patient with AF and heart block, greater immediate improvement in LV function is achieved with BiV or LV-RV offset stimulation than with single-site LV stimulation, presumably because VV dyssynchrony induced by LV-only stimulation is avoided in the setting of heart block.49 Acute predictors of a beneficial hemodynamic response to CRT were identified to be baseline extent of QRS delay (but not subsequent shortening with pacing) and mechanical dyssynchrony.41,50 LVFW rather than true anterior LV stimulation sites appear to elicit a more robust acute hemodynamic response.48 However, rigorous endocardial mapping has recently shown a high degree of individual variability for the best pacing site.51 The authors concluded that in a homogeneous group of patients with nonischemic dilated cardiomyopathy, the optimal pacing site cannot be predicted, and pacing from the coronary sinus or midlateral wall is rarely optimal. Speckle tracking analysis of torsion suggests that an acute improvement in LV twist after CRT predicts LV reverse remodeling.52 Similar findings in the PROMISE-CRT study support the hypothesis that acute changes in radial mechanical dyssynchrony are associated with LV reverse remodeling.53

RV SEPTUM

LV pressure (mm Hg)

RV APEX 120

120

80

80

40

40

0

0 0

100

200

300

0

LV pressure (mm Hg)

LV FREE WALL

100

200

300

BIVENTRICULAR

120

120

80

80

40

40

0

0 0

100

200

0

300

LV volume (mL)

100

200

300

LV volume (mL)

Intrinsic Paced Figure 12-1  Pressure-volume graphs from a patient with baseline left bundle branch block as a function of varying pacing sites. Data are shown for optimal atrioventricular interval (averaging 125 ± 48 msec) at each site; solid line, NSR control; dashed line, VDD pacing. The difference was negligible between right ventricular (RV) apex and septum pacing. However, left ventricular (LV) pacing produced loops with greater area (stroke work) and width (stroke volume) and a reduced systolic volume. The last finding is consistent with increased contractile function and thus elevation of dP/dtmax. These results were similar in a subset of patients with measurable data. (From Kass DA, Chen CH, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 30:1567-1573, 1999.)



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Controlled Trials of CRT Devices Table 12-2 summarizes the design, inclusion criteria, and results of the early controlled clinical trials of CRT-P and CRT-D devices. In general, inclusion criteria were similar: symptomatic, mostly NYHA Class III and IV heart failure (except REVERSE and MADIT-CRT, later trials that enrolled NYHA I and II patients), left ventricular ejection fraction (LVEF) of less than 0.35, prolonged QRS duration (>120, >130, or >150 msec), and stability of proved medical therapies for heart failure before enrollment.3,5,7-10,54-57 TABLE

12-2 

281

Only two early trials used epicardial LV leads, placed through limited thoracotomy for LV stimulation.4,54 The Multisite Stimulation in Cardiomyopathy–Sinus Rhythm (MUSTIC-SR) trial used a styletdriven coronary sinus lead; the other trials used over-the-wire leads to achieve LV stimulation through a coronary sinus branch vein.3,7-10,54-57 The earliest U.S. CRT study using an epicardial LV lead, the VIGORCHF trial, was not completed because of insufficient patient enrollment for the primary functional endpoint of peak oxygen uptake (peak Vo2). In addition, with the emergence of the coronary sinus branch vein lead, patients and physicians became reluctant to continue using

Early Controlled Trials of CRT Alone or with Implantable Cardioverter-Defibrillator (ICD) Enrollment (Pub) Dates 1998-1999 (2001)

Study (Location) Multisite Stimulation in Cardiomyopathy–Sinus Rhythm (MUSTIC-SR) (Europe)

Type (Duration) Prospective, randomized, single-blind crossover study of HF (3 months)

Multisite Stimulation in Cardiomyopathy–Atrial Fibrillation (MUSTIC-AF) (Europe)

Prospective, randomized, single-blind crossover VVIR-BiV study of HF (2-3 months)

1998-1999 (2002)

Pacing Therapies in Congestive Heart Failure (PATH-CHF) (Europe)

Longitudinal study of CRT with second placebo control phase; first and third periods are crossovers between LV and BiV (3 months) Crossover randomized trial of no CRT vs. CRT in LV only; 2 patient groups: QRS 120150 msec and QRS >150 msec (3 months)

1995-1998 (2002)

PATH-CHF II (Europe)

N* 67

NYHA >III LVEF 60 mm QRS ≥200 msec during ventricular pacing 6MWD 120 msec Sinus rate ≥55 bpm PR ≥150 msec

6MWD, peak Vo2, QOL, NYHA,† hospitalization, patient treatment preference, all-cause mortality, echo indices

59

Peak Vo2, 6MWD, NYHA, QOL†

41

86

NYHA II-IV LVEF ≤0.30 QRS ≥120 msec Optimal therapy for HF; patients with ICDs may be included

Peak Vo2, peak Vo2 AT, 6MWD, QOL, NYHA,† hospitalization

NYHA III-IV LVEF ≤0.35 LVEDD ≥55 mm QRS ≥130 msec Patients with pacing indication not admitted; stable optimal medical therapy NYHA III-IV LVEF ≤0.35 LVEDD ≥55 mm QRS ≥130 msec ICD indication

NYHA, 6MWD, QOL,† echo indices, peak Vo2, mortality, hospitalization, QRS duration, neurohormone levels

453

QOL, NYHA, 6MWD,† peak Vo2, echo indices, exercise duration, HF composite (death, HF hospitalization, NYHA, and patient global self-assessment), safety of CRT-D Combined all-cause mortality and all-cause hospitalization,† QOL, functional capacity, peak exercise performance, cardiac morbidity

369

Prospective, randomized, double-blind, parallel, controlled trial (6 months)

1998-2000 (2002)

Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLEICD) (U.S.)

Prospective, randomized, double-blind, parallel, controlled trial evaluating safety and efficacy of CRT in patients with HF and indication for ICD (6 months) Randomized (1:2:2), open-label, 3-arm study to determine if optimal drug therapy + CRT or drug therapy + CRT-D is superior to drug therapy alone (12 months)

1999-2001 (2003)

Open-label, randomized, controlled trial of CRT + optimal medical therapy vs. optimal medical therapy alone (mean: 29.4 mo)

2001-2003 (2004)

Cardiac Resynchronization in Heart Failure (CARE-HF) (Europe)

Endpoints 6MWD, peak Vo2, QOL, NYHA,† hospitalization, patient treatment preference, all-cause mortality, echo indices

1998 (2003)

Multicenter InSync Randomized Clinical Evaluation (MIRACLE) (U.S.)

Comparison of Medical Therapy Pacing and Defibrillation in Heart Failure (COMPANION) (U.S.)

Inclusion Criteria NYHA III LVEF 60 mm QRS ≥150 msec 6MWD 150 msec No indication for pacemaker or ICD HF hospitalization in past year NYHA III or IV LVEF ≤0.35 LVEDD ≥30 mm/m (height) QRS >150 msec or QRS ≥120 msec plus echo criteria of dyssynchrony; stable optimal medical therapy

All-cause mortality or unplanned cardiovascular hospitalization,† all-cause mortality or hospitalization for HF, NYHA, QOL, echo LV function, neurohormone levels, economic impact

1520

800

Results Improvements in 6MWD, peak Vo2, QOL, and NYHA; reduced hospitalizations; patients preferred CRT Improvements in 6MWD, peak Vo2, QOL, and NYHA; reduced hospitalizations; patients preferred CRT Improvements in exercise capacity, functional status, and QOL

In group with QRS 120-150 msec, no improvement In group with QRS >150 msec, improvements in Vo2, AT, 6MWD, and QOL Improvements in NYHA, 6MWD, QOL, LVEF, ventricular volumes, mitral regurgitation, peak Vo2; reduced hospitalizations Improvements in QOL, NYHA, and clinical composite endpoints; CRT-D safe to use

Stopped early because of reduced all-cause mortality and hospitalization with CRT; reduced all-cause mortality with CRT-D Improvements in morbidity/mortality and cardiovascular hospitalization

Modified from Saxon LA, De Marco T, Prystowsky EN, et al, Executive Summary: Resynchronization Therapy for Heart Failure. Executive Consensus Conference, May 2002. http:// www.hrsonline.org/positionDocs/CRT_12_3.pdf/. AT, Anaerobic threshold; BiV, biventricular; CRT-D, CRT with defibrillator; echo, echocardiographic; HF, heart failure; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; 6MWD, 6-minute walk distance; NYHA, New York Heart Association functional class; QOL, quality of life; Vo2, oxygen uptake. *Accrual or accrual goals. †Primary endpoint.

282

TABLE

12-3 

SECTION 2  Clinical Concepts

Study Endpoints in Trials of CRT Devices

Measure Functional status Heart failure progression Heart failure outcome

Endpoints Quality of life (QOL) 6-minute walk distance Cardiopulmonary exercise test Left ventricular ejection fraction (LVEF), ventricular volume Mitral regurgitation Serum catecholamines, brain natriuretic peptide Heart rate variability Hospitalization Mortality

a more invasive procedure for LV stimulation. The echocardiographic substudy, however, as with the first European Pacing Therapies in Congestive Heart Failure (PATH-I) study, demonstrated improvement in several measures of response to CRT, comparable to levels seen in studies using transvenous LV stimulation for CRT.7,40,54 The VIGORCHF trial demonstrated a decrease in LV and left atrial volumes as well as improvements in LV outflow tract and aortic velocity time integrals and myocardial performance indices with just 12 weeks of CRT. The severity or grade of mitral regurgitation as well as mitral deceleration (a measure of improvement of diastolic LV function) also improved. In the two early U.S. trials that were the basis for attaining the initial approvals from the U.S. Food and Drug Administration (FDA) for CRT-defibrillator (CONTAK CD and MIRACLE-ICD; see later), patients with NYHA Class II were included, but FDA labeling was not requested for this patient subset and was granted only for patients with NYHA III and IV.8,57,58 Exclusion criteria included the presence of an implanted device and requirement for bradycardia pacing support or permanent AF. The early U.S. trials used parallel design; devices were implanted in all patients, who were then randomly assigned to “CRT on” or “CRT off ” status for 6 months. Two principal investigators at each enrolling center were designated in most trials, so the physician managing the medical therapies (heart failure) was blinded as to the treatment assignment, and the implanting physician (electrophysiologist) followed the device performance. The study endpoints in CRT trials have evolved over time. Although all trials have included safety and efficacy endpoints, the initial trials assessed only measures of heart failure functional status, LV systolic function (LVEF), and LV remodeling (LV end-systolic and diastolic dimensions). The later, larger studies targeted mortality and hospitalization endpoints (Table 12-3). The use of these multiple endpoint measures is standard for heart failure trials evaluating medical therapies and has highlighted the issue of defining “benefit” from CRT.1,6 One can define “response” as consisting only of symptom improvement, or one can require that all three measures of heart failure show benefit, as outlined in Table 12-3. To complicate the issue further, no 1 : 1 correlation seems to exist between these measures of response. Again, the CONTAK CD and MIRACLE-ICD studies enrolled some patients with NYHA Class II in addition to those with NYHA III and

Multisite Stimulation in Cardiomyopathy Studies The 2001-2002 European Multisite Stimulation in Cardiomyopathy (MUSTIC) studies provided the first long-term controlled trial data on the efficacy of CRT, delivered as BiV stimulation, for 3-month intervals, compared with normal sinus rhythm or continuous RV-based pacing in AF patients.3,56 Figure 12-2 illustrates the crossover study design of the MUSTIC and MUSTIC–Atrial Fibrillation studies. Although only 48 patients completed the two 3-month crossover study periods, all leads placed in the trial were transvenous, with no significant safety issues. Eligibility for patient enrollment included NYHA Class III with QRS longer than 150 msec. In patients with normal sinus rhythm, quality of life (QOL) score improved by 32%, 6-minute walk distance (6MWD) improved by 23%, and peak Vo2 improved by 8%. Although the study was not statistically powered to determine a reduction in rate of hospitalization, hospitalizations after CRT initiation decreased by two thirds.3 At the end of the crossover phase, patients (who were blinded to treatment) were asked to choose which 3-month period they preferred; 85% chose the pacing period during which they had been assigned to VDD, 10% had no preference, and 4% chose ODO (no pacing). Four patients had severe episodes of congestive heart failure exacerbation during the ODO pacing period. In the patients with permanent AF and continuous RV pacing, 37 of 59 who underwent CRT implantation completed both 3-month crossover phases and had documentation of 97% to 100% CRT delivery. Because of the significant number of dropouts (42%), the intention-to-treat analysis did not show a significant improvement with CRT. In the 37 patients with a complete data set and documentation of CRT, QOL measure did not improve, but 6MWD and peak Vo2 increased significantly, by 9% (P = .05) and 13% (P = .04), respectively.56 When the entire 6-month crossover phase is considered, 10 of 44 patients were hospitalized for heart failure decompensation during RV pacing, whereas only three were hospitalized for heart failure during the CRT period; 85% of patients preferred the CRT period. There was a trend toward a better QOL among patients with CRT (11% improvement; P = .09). Subsequent uncontrolled trials in patients with permanent AF and continuous RV pacing have shown a more robust improvement in these measures, as well as a reverse-remodeling response with CRT compared with RV pacing alone.60,61 The PAVE trial also showed improvement with CRT but did not require heart failure caused by systolic dysfunction for enrollment.62

Inactive pacing

Implantation

Baseline

IV functional status. In the NYHA II group, significant improvements in measures of functional status were not uniformly observed, although some patients experienced a positive reverse-remodeling response.57,58 This has been confirmed in the much larger REVERSE study, where CRT in patients with NYHA Class I/II heart failure resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes in patients with nonischemic cardiomyopathy.15 Clearly, CRT has a positive effect on decreasing LV size, and the subsequent MADITCRT study demonstrated that CRT favorably alters the natural history of heart failure by reducing hospitalization.14,59

CO1

CO2

Randomization Active pacing

4 weeks

2 weeks

12 weeks

12 weeks

Figure 12-2  Crossover study design of MUSTIC studies. Patients were randomly assigned to 3 months each of inactive pacing (ventricular, inhibited at basic rate of 40 bpm) and active pacing (atriobiventricular); CO1, end of crossover period 1; CO2, end of crossover period 2. (From Cazeau S, Leclercq C, Lavergne T, et al: Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873-880, 2001.)



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Pacing Therapies in Congestive Heart Failure The two Pacing Therapies in Congestive Heart Failure (PATH-I and PATH-II) European studies were groundbreaking in that chronic device programming was based on acute hemodynamic measures of cardiac performance. In addition, these same measures were used to optimize AV-delay programming.54,55 Begun in 1995 and completed in 1998, these trials enrolled patients with NYHA Class III or IV congestive heart failure, sinus rate higher than 55 beats per minute (bpm), and QRS duration longer than 120 msec. In PATH-I, patients were crossed-over between LV and BiV stimulation with a 1-month interval of no stimulation. A second study phase lasted 9 months and used the CRT mode that achieved what the follow-up physician determined was the most optimal mode. There were no differences in the acute or chronic response of patients whether programmed to LV or BiV CRT. Statistically significant improvements in peak Vo2 anaerobic threshold (24% improvement; P < = .001), 6MWD (25%; P < .001) and QOL (59%; P < .001) were observed at 3 months and 12 months of follow-up. Of 29 patients followed to 12 months, 21 improved from NYHA Class III or IV to Class I or II. Heart failure hospitalizations decreased from 76% in the year before implantation to 31% during the year after implantation. Importantly, LBBB was the type of conduction delay in more than 87% of patients; most CRT trials enroll up to 30% of patients with either intraventricular condition delay (IVCD) or RBBB.4-6,9 This difference may explain why LV stimulation in PATH-I resulted in only an equivalent response to BiV stimulation to achieve CRT, although the study was not statistically powered to demonstrate a difference between the two modalities, and the long-term data were pooled from both modes. The best that one can conclude is that in small numbers of patients who undergo hemodynamic optimization programming during implantation that shows equivalence between LV and BiV stimulation to achieve CRT, longterm symptom responses appear to be equivalent. Extending the observations from PATH-I, PATH-II evaluated LV-only CRT compared with no CRT in a 3-month crossover design.55 In all patients with LBBB (88% of subjects), LV pacing was identified as the optimal single-chamber pacing mode (compared with RV only) on the basis of immediate hemodynamic response, and AV delay timing was optimized in all patients. Patients were further divided by QRS duration according to whether the QRS was more than 120 msec but less than 150 msec (“short QRS”) or more than 150 msec (“long QRS”). Unfortunately, only 35 patients, slightly less than one half of all patients enrolled, completed both 3-month crossover intervals. Nonetheless, the study did demonstrate improvements in peak Vo2, anaerobic threshold, 6MWD, and QOL in the patients with long QRS. For example, 71% of the long-QRS group and 38% of the short-QRS group had an increase in the peak Vo2 of more than 1 mL/kg/min with active pacing. This was the first study to demonstrate that QRS duration predicts the magnitude of symptom response to CRT delivered as LV-only stimulation. Subgroup analysis of all but one of the larger U.S. long-term studies of BiV CRT also suggests that the magnitude of benefit may be greater in patients with longer QRS duration at baseline.5,8-10,57 The EARTH trial will compare chronic LV to BiV stimulation and RV stimulation and assess differences in symptoms and in echocardiographic and metabolic exercise test performance, according to stimulation mode in CRT candidates.63 Multicenter InSync Randomized Clinical Evaluation The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study was the only U.S. trial of CRT for heart failure that used a CRTpacemaker device only.5 The number of patients randomly allocated in U.S. clinical trials was much greater than those in the European trials until the CARE-HF trial. All 453 patients enrolled in the MIRACLE study underwent implantation of the CRT device and then random assignment to “CRT on” or “CRT off ” status for 6 months. Figure 12-3 illustrates the study design of the MIRACLE, MIRACLE-ICD, and CONTAK CD U.S. trials. Unlike the COMPANION trial, in which patients were randomly assigned after consent was obtained and before

CRT

CONTAK CD Implantation

Baseline 6MW, CPX

>30 days

6 months

CRT

No CRT

CRT

MIRACLE ICD Baseline 6MW

283

Implantation

Baseline CPX

0–7 days

6 months

CRT

No CRT

CRT

MIRACLE Baseline 6MW, CPX

Implantation

6 months

CRT

No CRT Figure 12-3  Study design of three U.S. trials. CONTAK CD Biventricular Pacing Study (CONTAK CD), Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD), and Multicenter InSync Randomized Clinical Evaluation (MIRACLE); 6MW, 6-mile walk distance; CPX, cardiopulmonary exercise test; CRT, cardiac resynchronization therapy.

device implantation, these earlier U.S. trials randomly assigned patients only after a successful CRT implant. The U.S. trials also employed strict protocol-mandated criteria on appropriate and stable heart failure medical regimen requirements before consent and device implantation. The primary endpoints, including 6MWD, QOL score, and NYHA functional class, were all favorably influenced by CRT, and the effects of CRT were apparent as early as 1 month after therapy initiation. Patients who underwent CRT showed 13% improvement in 6MWD, 13% improvement in QOL, about 1-mL/kg/min improvement in exercise capacity, and an increase in total exercise time of approximately 60 seconds. Unlike the European and acute hemodynamic studies, neither baseline QRS duration nor type of bundle branch block influenced response to CRT in the MIRACLE study. The secondary endpoints, Vo2 and LVEF, also improved with CRT, as did episodes of heart failure worsening, including heart failure hospitalizations. At 6 months, CRT was associated with decreased LV end-diastolic volume (LVEDV) and LV end-systolic volume, reduced LV mass, increased LVEF (+3.6%), decreased mitral regurgitation jet area (−2.5 cm2), and improvement in the clinical composite heart failure score. Improvements in LVEDV and LVEF were twofold greater in patients with nonischemic cardiomyopathy. CRT resulted in significant improvements in NYHA class and LVEF, regardless of age.64 CONTAK CD and Multicenter InSync ICD Randomized Clinical Evaluation Concurrent with the MIRACLE trial enrollment, two large-scale trials of CRT-defibrillator for patients with heart failure and primary or secondary indications for an ICD were also enrolling subjects, the Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLEICD) and the CONTAK CD Biventricular Pacing Study. Unlike the MIRACLE study, the 950 patients randomly assigned to different therapies in the CRT-D studies had primarily ischemic cardiomyopathy (61%-75%,) and about one half of the patients had a secondary indication for the ICD.8,57 In patients with NYHA Class III or IV status, both studies demonstrated improvements in functional measures of heart failure status. An ongoing debate concerns the impact of CRT and

284

SECTION 2  Clinical Concepts

reverse remodeling on ventricular arrhythmias. Neither study showed a difference in the incidence of treated episodes of ventricular tachycardia or ventricular fibrillation (VT/VF) with CRT on or off, indicating a neutral effect of CRT on the arrhythmia substrate early after device implantation. A subsequent analysis of the MIRACLE-ICD data indicated that patients with secondary ICD indications experienced more ICD therapies for VT, whereas those with primary ICD indications had more therapy for VF.65 The incidence of ICD therapy, as expected, was higher in those with secondary prevention indications. In CONTAK CD, the incidence of ICD therapy over the 6-month follow-up was 16% for both VT and VF. In contrast, in the InSync ICD Italian Registry, a significant reduction in ventricular arrhythmias and shock therapies was reported and correlated with the degree of ventricular remodeling at 12 months.66 Similar findings were seen in the InSync-III Marquis study, in which anatomic responders to CRT demonstrated fewer premature ventricular contractions (PVCs), runs of PVCs, and therapies for VT/VF.67 Improvements in LVEF and ventricular size and dimension and degree of mitral regurgitation were noted in the VIGOR-CHF, MIRACLE, MIRACLE-ICD, and CONTAK CD studies, all of which had core echocardiographic laboratories performing analysis, with excellent intraobserver and interobserver variability.7,40 As mentioned, even the patients with NYHA Class II benefited from CRT in terms of an echocardiographic response of reverse remodeling.16,57 These CRTrelated effects were independent of the use of β-blocker therapy.7 This finding suggests that CRT can exert beneficial effects on the remodeling process across a spectrum of heart failure severity, similar to that observed with angiotensin-converting enzyme (ACE) inhibitor therapy.1 A subsequent study of the effects of CRT on ventricular function, volume, and dimension has shown that the beneficial effects occur as early as 4 weeks and are sustained for a time even after CRT is suspended, indicating that CRT affects cardiac structure.68 Another measure of heart failure progression, level of plasma neurohormones, did not improve or worsen with CRT in the MIRACLEICD or MIRACLE study. This neutral effect may be a result of optimization of medical therapy with neurohormonal antagonists before device implantation or inadequate duration of follow-up.7

Comparison of Medical Therapy, Pacing, and Defibrillation on Heart Failure The Comparison of Medical Therapy, Pacing, and Defibrillation on Heart Failure (COMPANION) study was the first and only U.S. trial statistically powered to assess the impact of CRT on hospitalization and mortality endpoints.9,69 During COMPANION’s design, it was unclear whether ICD therapy in addition to CRT would reduce mortality in advanced heart failure compared with medical therapy. Therefore, the study randomly assigned patients to optimal medical (pharmacologic) therapy for heart failure (OPT), a CRT with pacemaker (CRT-P) alone, or a CRT with an ICD (CRT-D). The patients were assigned in a 1 : 2 : 2 ratio, respectively, to maximize the number of patients receiving devices. Statistical power was insufficient to compare CRT with CRT-D directly (both were compared with OPT), but the highest-order secondary endpoint was mortality. To enrich the anticipated event rate in the trial, patients also needed to have heart failure hospitalization in the previous year, but not in the month preceding enrollment, and to be receiving stable medical therapy at enrollment. Unlike the prior trials of CRT, patients were assigned for therapy and data were analyzed after they had provided informed consent, not after they had undergone a successful implantation. Figure 12-4 provides the design of the COMPANION study, and Table 12-4 lists the clinical characteristics of COMPANION patients. As with MIRACLE patients, and unlike those in the CRT-D studies, an equal proportion of patients in COMPANION had both ischemic and nonischemic etiologies for LV dysfunction. This was the first trial to enroll patients with advanced heart failure who were medically treated with “triple therapy,” consisting of ACE inhibitors, β-receptor blockers, and aldosterone antagonists. The primary study endpoint was a composite of all-cause hospitalization and mortality, and the secondary endpoint was mortality (1520 patients enrolled). Figure 12-5 shows the event-free survival curves for the primary and secondary endpoints and demonstrates the 20% 12-month reduction in death or hospitalization from any cause observed with both CRT and CRT-D devices compared with OPT. The risk of one of these events was 68% in OPT patients, attesting to the

Follow-up n = 1520

Follow-up

Follow-up

1

• OPT Baseline

Randomization Stratification

Implantation

Follow-up

Follow-up

Follow-up

Follow-up

Follow-up

2  • OPT • Resynchronization therapy Implantation

Follow-up

2  • OPT • Resynchronization therapy w/ICD backup 120 msec and the presence of at least two of three markers of dyssynchrony: (1) aortic preejection delay



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Variable

Hazard Ratio for Death from or Hospitalization for Any Cause

No. of Patients Pharmacologic Pacetherapy maker (n308) (n617)

Age 65 yr 65 yr Sex Male Female Cardiomyopathy Ischemic Nonischemic NYHA class III IV LVEF 20% 20% LVEDD 67 mm 67 mm QRS interval width 147 msec 148–168 msec 168 Bundle branch block Left Other Heart ratio 72 beats/min 72 beats/min Systolic BP 112 mm Hg 112 mm Hg Diastolic BP 68 mm Hg 68 mm Hg ACE inhibitor use No Yes β-blocker use No Yes Loop diuretic use No Yes Spironolactone use No Yes

Hazard Ratio for Death from or Hospitalization for Any Cause

287

Hazard Ratio for Death from Any Cause

Pacemakerdefibrillator (n595)

123 185

272 345

272 323

211 97

415 202

401 194

181 127

331 285

325 270

253 55

537 80

512 83

143 165

324 293

282 313

133 122

257 266

248 237

115 111 82

209 203 205

178 232 185

215 93

426 190

434 161

161 147

318 299

315 280

164 144

347 270

307 288

178 130

328 289

316 279

96 212

186 431

183 412

104 204

196 421

193 402

17 291

36 581

20 575

139 169

288 329

267 328 0.0

0.5 Pacemaker better

1.0

1.5 0.0

Pharmacologic therapy better

0.5 Pacemakerdefibrillator better

1.0

1.5 0.0

Pharmacologic therapy better

0.5

1.0

Pacemakerdefibrillator better

1.5

2.0

2.5

Pharmacologic therapy better

Figure 12-6  Patient characteristics and hazard ratios in COMPANION study. Hazard ratios and 95% confidence intervals for the primary endpoint (death from or hospitalization for any cause) and secondary endpoint (death from any cause) according to baseline characteristics of COMPANION patients. Echocardiographically determined values for left ventricular end-diastolic dimension (LVEDD) were not available for all patients. ACE, Angiotensin-converting enzyme; BP, blood pressure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association functional class. (From Bristow MR, Saxon LA, Boehmer J, et al: Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators: Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004.)

greater than 140 msec, (2) interventricular mechanical delay more than 40 msec, and (3) delayed activation of the posterolateral LV wall, as judged by M-mode and pulsed-wave Doppler. The incremental benefit of a BiV defibrillator (CRT-D) over a BiV pacemaker (CRT-P) in patients with LV systolic dysfunction remains uncertain. The CRT-D device is more expensive than a CRT-P device

and has higher long-term costs because of a shorter battery life. Decision-analysis models suggest that the cost of both is within acceptable standards for QOL years, but that the CRT-P is associated with less costs than the CRT-D device.77-79 Appropriate ICD therapy in CRT patients predicts a much worse outcome, and the number needed to treat (NNT) analysis in COMPANION patients favors the placement of

288

SECTION 2  Clinical Concepts

Percentage of patients free of death from any cause or unplanned hospitalization for a major cardiovascular event

100

75 Cardiac resynchronization 50

Medical therapy

25

P 64 cycles). Within 1 year after implantation, mortality rate was 11.7%. Although the incidence of sustained VT was only 4.3%, these patients had a significantly higher risk of all-cause mortality and sudden cardiac death than those without sustained VT. This study highlights the value of remote monitoring to detect patients for urgent upgrade, although this is also associated with increased costs, and not all patients will have VT detected before a sudden fatal arrhythmia. Also, sustained episodes of VT could worsen heart failure symptom status and result in syncope.



289

12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators 1.00

1.00

CRT

CRT 0.75

Medical therapy Hazard ratio 0.55 (95% CI 0.37–0.82, P = 0.003)

.50

Survival

Survival

.75

.25

Hazard ratio 0.54 (95% CI 0.35–0.84, P = 0.006)

0.50

0.25 CRT = 38 HF deaths (9.3%) Medical therapy = 64 HF deaths (15.8%)

0 0

A

Medical therapy

400

800

1200

CRT = 32 sudden deaths (7.8%) Medical therapy = 54 sudden deaths (13.4%) 0.00

1600

Time (days)

0

400

800

B

1200

1600

Time (days)

Figure 12-8  Kaplan–Meier estimates in CARE-HF extension phase. CRT-P patients had reduced risk of sudden death at extended follow-up of 37 months. A, Time to death from worsening heart failure. B, Time to sudden death. (From Cleland JGF, Daubert JC, Erdmann E, et al: Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase] Eur Heart J 27:1928-1932, 2006.)

Two pivotal trials studied the effect of CRT in patients with mild heart failure, REVERSE and MADIT. Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study was the first randomized controlled trial (RCT) of CRT in NYHA Class II patients or in NYHA Class I patients with previous heart failure symptoms.59 Patients were randomized to CRT on or off, with a clinical composite endpoint scoring patients as improved, unchanged, or worsened; intergroup efficacy of CRT was limited to percent patients who worsened at 12 months, because asymptomatic Class I patients cannot improve their symptom status. The prospectively powered secondary endpoint was LV endsystolic volume index (LVESVI). The mean LVEF was 26.7%, mean QRS was 153 msec, and all patients were in sinus rhythm receiving OPT. A CRT-D was implanted in 83% of successfully implanted patients, with even distribution between ischemic and nonischemic arms. AV delay was optimized by echocardiography in all patients, regardless of randomization assignment, before the final programming. Although there was no significant difference in the primary endpoint between the two groups, the active CRT group benefited from reduced heart failure hospitalization and improved ventricular function, with a highly significant reduction in LVESVI59 (Fig. 12-9). The REVERSE European cohort of 287 patients had a longer follow-up over 24 months and were much younger with fewer comorbidities than the non-European sample. This cohort demonstrated a significant difference in primary endpoint between the two study groups, which became evident as early as 6 months and persisted for 24 months. A longer follow-up may have allowed the therapeutic effects of CRT to manifest in patients expected to have a slow progression of disease.15 Multi-Center Automatic Defibrillator Implantation Trial–CRT The Multi-Center Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) study was an RCT comparing CRT-D devices with RV-based ICDs in patients with QRS greater than 130 msec, ejection fraction (EF) of 30% or less, sinus rhythm, ischemic etiology (NYHA Class I or II) or nonischemic etiology (NYHA II only), and a guideline indication for an ICD.14 The primary endpoint was a composite of all-cause mortality and nonfatal

heart failure events (1820 patients enrolled). Over an average follow-up of 2.4 years, the CRT-D group had a 34% risk reduction in the primary endpoint. The trial was stopped early once the interim analysis identified the superiority of CRT-D (Fig. 12-10). The primary endpoint was driven almost entirely by a reduction in the risk of heart failure events, because the annual mortality rate was only 3% in each treatment group. The benefit was evident in patients with both ischemic and nonischemic cardiomyopathy. The outcome curves diverge within the first 2 months, suggesting an early benefit on heart failure hospitalization and other events requiring treatment. Interestingly, prespecified subgroup analysis showed that women derived a greater benefit from CRT-D independent of QRS duration. Patients with QRS of 150 msec or greater derived greater benefit, in keeping with previous trials. No benefit was observed among patients with right bundle branch block. Echocardiographic evaluation showed significant reductions in LV volumes and a mean improvement in EF of 11% at 1 year. Importantly, the results cannot be attributed to an increase in RV pacing–induced heart failure in the ICD group because

% of patients hospitalized for HF

PREVENTION OF HEART FAILURE EVENTS

15

P = 0.03

Hazard ratio = 0.47

10 CRT-OFF 5 CRT-ON 0 0

3

6

9

12

Months since randomization No. at risk CRT-OFF CRT-ON

191 419

187 415

181 411

176 409

119 251

Figure 12-9  Hazard ratios in REVERSE study. Time to first heart failure hospitalization in first 12 months in CRT-OFF and CRT-ON groups. (From Linde C, Abraham WT, Gold MR, et al: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol l52:1834-1843, 2008.)

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SECTION 2  Clinical Concepts

Probability of survival free of heart failure

1.0

The significant improvement in mortality and heart failure hospitalization is a novel observation, as the MADIT-CRT study showed benefit only in heart failure hospitalization. The mean follow-up was longer in the RAFT study and this or other differences in the study populations not apparent from the clinical characteristics data may explain the improvement in mortality observed in RAFT and not in MADIT-CRT. The data from RAFT certainly lend support to the use of CRT in patients with less manifest symptoms of heart failure who have depressed ventricular function and QRS delay. A final important finding of the RAFT study is that the rate of adverse events within 30 days of device implantation was significantly higher in patients in the ICD-CRT group compared to the ICD group. These data indicate that even though LV coronary sinus vein lead implantation can be successfully achieved with current tools by the majority of implanting electrophysiologists, the procedure still carries significant incremental risk compared to a standard left-sided ICD implant. This is particularly important as, in practical terms, the patient populations most apt to increase as a result of the RAFT and MADIT-CRT studies are those undergoing ICD device change-outs with minimally symptomatic heart failure who have continuous RV pacing or native conduction delay.

0.9 CRT-ICD

0.8 0.7

ICD only

P 3.5 >3.5 >3.5 >3.5 >3.5 >3.5 >3.5

Atrium

Impedance (Ω) 480 500 500 480 500 470 470 480 480 480

Amplitude (mV) PACED PACED PACED PACED PACED PACED PACED PACED PACED PACED

Ventricle Impedance (Ω) 680 710 710 710 680 670 710 710 720 680

prevent conduction down the AV node, or simply to enhance the ability to achieve higher pacing rates while maintaining AV synchrony. Various functions (e.g., rate hysteresis, therapeutic pacing rates) in response to sudden decreases in native heart rates complicate these systems even further. Most recently, the widespread use of multichamber pacing for cardiac resynchronization and atrial fibrillation suppression has created an even greater degree of complexity. In the modern pacemaker, interpretation of the paced rhythm requires knowledge of the basic timing intervals. A variety of refractory periods, including postventricular atrial refractory period (PVARP), postventricular atrial blanking period, ventricular refractory period, ventricular blanking period, and paced and sensed A-V intervals, must be considered. Some intervals may change depending on the rate, such as A-V interval, atrial escape interval (when sensor driven or with special features), and PVARP. The clinician also needs to be aware of a number of device-specific responses to protect the system from a variety of anticipated but undesirable behaviors or clinical events. These include crosstalk, the initiation of pacemaker-mediated tachycardia by a premature ventricular beat, mode switching, and multiblock upper rate behavior. To facilitate interpretation of the paced rhythm, almost all modern pacing and ICD systems incorporate the ability to transmit information regarding real-time pacing system behavior to the programmer. These data are displayed on the programmer screen and may also be printed as well. Both paced and sensed events are communicated to the programmer. Displayed as a series of positive or negative marks, with or without alphanumeric annotation, these are generically termed event markers. They have the greatest diagnostic value when superimposed above or below a simultaneously recorded surface ECG (Fig. 29-6). Some systems also display the duration of the atrial and

850

SECTION 4  Follow-up and Programming

ECG Controls

Programmed Parameters

Surface ECG ................................... On Position ........................................... 1 Gain .......................................... 0.25 Filter ............................................ On Markers ........................................... On Position .......................................... 2 IEGM ............................................... Off Position ........................................... 3 Gain ............................................... 5 Configuration ................................. -Sweep Speed ................................... 25

Mode ......................................... DDDR Base Rate ........................................ 65 A-V Delay ....................................... 300 P-V Delay ....................................... 200 Magnet Response ......... Temporary Off Temporary 30 .................................. Off

mV/div

ppm ms ms

mV/div mm/s

1.0 Second

A 273

A R

R

426

627 908

281

A R 627 901

274

A R

R

464

626 900

274

A R 627 901

274

A R 626 900

274

A R 631 896

265

R

R

449

630 908

Figure 29-6  Surface ECG and simultaneous event markers. Telemetry shows an atrial-paced rhythm with intact atrioventricular nodal conduction and isolated ventricular ectopic beats. Key programmed parameters are shown at the upper right, and recording parameters at the upper left (IEGM, intracardiac electrogram). The numbers refer to the millisecond intervals automatically measured and displayed by the programmer. The horizontal lines that follow the alphabetic label (A, atrial-paced output; R, sensed ventricular event) represent the length of the programmed or functional refractory period. Data are from a Pacesetter Trilogy DR+ Model 2360 (St. Jude Medical CRMD, Sylmar, Calif ).

ventricular refractory periods and interval measurements. Others show events that are sensed during the refractory period even though they do not play a role in altering the system timing (i.e., they are sensed but not used). Events may be displayed either in real time or after the tracing has been frozen on the programmer screen using cursors to identify the interval of interest. If the real-time monitor screen method is used to show the rhythm and event markers, the tracing may be frozen and then printed for inclusion in the medical record. Event markers (also called marker channels, annotated event markers, and main timing events by various manufacturers) are most effectively used when they are displayed with a simultaneously recorded ECG rhythm.22-25 Without the ECG, the event marker simply reports the behavior of the pacemaker. This information is valuable in showing that an output has been released or that sensing has occurred. It does not confirm that the stimulus effectively resulted in capture, or that a sensed event was a true atrial or ventricular depolarization. The presence of an output marker does not confirm that the stimulus even reached the heart. The output marker serves only to confirm that the pacemaker delivered a stimulus from its output circuit. This notation is transmitted directly from the pacemaker to the programmer by way of the telemetry module. An open circuit (e.g., a fractured conductor coil) may preclude the output pulse from reaching the heart, but the pacemaker would indicate that an output pulse was released. Similarly, a native depolarization may not be sensed, allowing the pacing stimulus to be released at a time when the myocardium is physiologically refractory. If the markers reported that an event was sensed on the atrial channel and was followed by a ventricular output pulse after a preset delay (known as P-wave synchronous ventricular pacing or tracking), the clinician would know that the pacemaker was capable of sensing in the atria and pacing in the ventricles. Without a simultaneously recorded ECG, it would be impossible to determine whether the pacemaker was responding to inappropriate signals on the atrial channel, whether the ventricular stimulus was effective, or whether a native QRS complex was present but not sensed. Therefore,

telemetered event markers are most effective when displayed with a simultaneously recorded ECG. Event Marker Displays A variety of different displays have been used over the years. Although not intended for this purpose, the simplest event marker for sensed events was achieved with triggered mode pacing, particularly if the output configuration was unipolar. A sensed event would be marked by the simultaneous release of a pacing stimulus coincident with sensing. This was easily recorded on the ECG, because the stimulus artifact distorted the morphology of the native sensed complex. The next evolutionary step in this technology involved the pacemaker emitting a series of subthreshold stimuli of varying amplitudes to represent the release of an output pulse, a sensed event, and the end of a refractory period. Both these systems, the triggered mode and the series of markers, were limited by the signals requiring an intact lead system, to allow the pulse to be delivered to the heart through the lead and subsequently recorded for display by the ECG. With a bipolar output pulse, the small artifact might not be readily visible, particularly in the triggered mode, because it would be obscured by the larger native complexes. In addition, if there were an open circuit (most often a conductor fracture) or an internal insulation failure involving a bipolar lead, no marker would be visible. The next improvement was to transmit coded signals representing paced and sensed events from the pacemaker to the programmer. The programmer reconstituted these signals into a series of varyingamplitude pulses or alphanumeric labels representing paced or sensed events. These could be either displayed on a monitor screen or recorded using a printer integral to the programming system, which allowed for the simultaneous recording of a surface ECG acquired by way of a separate set of cables. The simultaneous ECG and markers allowed the clinician to correlate the behavior of the pacemaker directly with the patient’s rhythm, to determine whether the system is functioning properly. A calibration signal composed of a series of



29  Pacemaker Troubleshooting and Follow-up Marker codes Atrial Pace (AP) Atrial Sense (AS) Atrial Refractory Sense (AR) Vent. Refractory Sense (VR) Vent. Sense (VS) Vent. Pace (VP)

→ → → → → →

A A A P S R

C H

V V V R S P

Figure 29-7  Example of formerly used event marker annotation. Lines of various amplitude are used to designate paced, sensed, and refractory events. Lines above the baseline are used to describe atrial events, and lines below the baseline to describe ventricular events. This type of annotation has been made obsolete by the current annotation systems.

different amplitude pulses or a legend of the cryptic labels allowed the clinician to interpret the various markers (Fig. 29-7). In an early series of markers, the largest pulse represented a pacing output, the intermediate one indicated a sensed event, and the smallest represented either the end of the refractory period or a sensed complex that occurred during the refractory period. With the advent of dual-chamber pacing systems, a marker pulse extending above the baseline identified atrial events, and ventricular events were labeled with a pulse extending below the baseline. This type of marker system has become obsolete, and there are very few devices remaining as active implants that use this scheme. A further refinement to this system was the addition of alphanumeric annotations, which made the simple (yet cryptic) system just described obsolete. Two common sets of notations have been used and are summarized later. These are not the only possibilities, because some manufacturers use a unique set of symbols to identify paced and sensed events, with the location of the symbol on the recording identifying whether it represents an atrial or a ventricular event. Others have expanded on the set of labels and provide, on command, a detailed explanation. One method for single-chamber pacing systems with event marker telemetry uses the letter P to reflect a paced event and S to represent a sensed event. This may cause confusion with other dual-chamber systems in which the letter P reflects a sensed atrial event indicative of a native P wave (with which most medical personnel are familiar, based on their knowledge of the standard ECG). The interpretation of the alphanumeric event markers is often product specific, and the clinic personnel who evaluate the pacing system must take this into account (Fig. 29-8). In the case of dual-chamber pacing or when the pacemaker knows that it is providing atrial pacing and sensing, a native atrial depolarization may be identified as either the letter P or the combination AS. P is taken from the standard ECG identifier for an atrial depolarization. AS is one abbreviation for an atrial sensed event. An atrial stimulus may be identified by either the letter A or the combination AP for atrial paced event. Analogous lettering is used on the ventricular channel. Again, singlechamber pacing in some systems might still use the letters P to represent a paced event and S to refer to a sensed event. Other systems use R to refer to a native ventricular depolarization, which is generically called an R wave on the standard ECG. This may also be identified by the letter combination VS for a ventricular sensed event. The letter V in one system might be used to represent a ventricular pacing stimulus, whereas the identical event may be labeled VP (for ventricular paced event) in other systems. Other symbols may be used for a paced or sensed event and are usually displayed with an identifying key on the resultant printout. Each paced or sensed event may also be identified by a vertical line, going up in the case of atrial events and down for ventricular events. In some cases, a difference in the amplitude of these lines has been retained in conjunction with the alphanumeric lettering. Indeed, as the

851

complexity of the devices increases, the variety of symbols and letters identifying specific events and behaviors is also increasing (see Fig. 29-8). In many systems, interval measurements between the various events are either calculated automatically and displayed, or measured after cursors are aligned with specific events. There may be a time delay between the actual sensed or paced event and the release of the event marker. This is caused by the finite period that is required for the pacemaker to recognize the event and then transmit the appropriate information to the programmer through the telemetry channel. In most cases, priority is given to the normal function of the pacemaker, with the diagnostic marker feature being delayed. Differences of up to 40 msec between the actual event and the resultant marker have been noted. Laddergramming Laddergramming is an advanced adjunct to the interpretation of clinical arrhythmias. It was incorporated in some programming systems by using the known programmed parameters of the pacemaker combined with the event marker information telemetry from the implanted pacemaker23-26 (Fig. 29-9). For all the elegance of these graphic interpretations of the pacemaker’s behavior, they still require the simultaneously recorded ECG rhythms. Although the pacemaker may be functioning normally, in that it is behaving properly with respect to its programmed parameters, failure to capture or properly sense would not be diagnosed from the various diagrams and markers without the simultaneously recorded surface ECG.27 Laddergramming has become a teaching tool at this time, because no programmers currently provide this level of graphic description. Event Marker Limitations Several limitations are associated with event marker telemetry. First, used alone, markers report the behavior of the pacemaker but do not allow the clinician to determine whether this behavior is appropriate for the patient.27 In this regard, markers are analogous to the hand-held digital counters that report pacing rates and intervals. The counters only detect and report the pacing stimuli, not whether these output pulses are effective in causing a cardiac depolarization, or whether native events are properly and consistently sensed. A long interval between consecutive pacing stimuli could reflect normal function because the pacemaker responded appropriately to a native complex, or it could represent a system malfunction with oversensing or no output (e.g., from intermittent lead fracture). Neither event marker telemetry nor the digital counters should be used independently of a simultaneously monitored ECG rhythm. The second limitation is that the report of a stimulus output does not mean that there was appropriate capture. Confirmation of capture requires an ECG or concomitant hemodynamic pulse monitoring. In addition, the markers may report that the pacemaker is sensing a signal, but if this signal is not visible on the surface ECG, there is cause for concern. Is it an appropriate signal that the pacemaker should be sensing (some intrinsic atrial rhythms may not be visible on the specific lead that is being monitored), or is the system responding to an inappropriate or nonphysiologic signal, such as the make-break potentials associated with a breach of the internal insulation in a coaxial bipolar lead? Most pacemaker event marker telemetry is limited to real-time recordings. The markers must be telemetered from the pacemaker to the programmer or another display system while the rhythm is being actively monitored. Neither the pacemaker nor the programmer can retrospectively provide markers for a previously recorded rhythm. If the pacemaker is responding to events that are not visible on the surface ECG, the event marker simply confirms this fact but does not identify the specific signal. An evaluation of sensed but otherwise invisible events requires intracardiac electrogram telemetry or an invasive procedure to record the signal from the implanted lead. Many premium-level pacemakers can store

852

SECTION 4  Follow-up and Programming

Event Marker Annotation Legend AS AP VS VP S P Hy PVC () Sr ↑ ↓ → Tr Ns FB MT PVP→ PMT-B Output↓ ATR↑ ATR↓ ATR-FB ATR-Dur ATR-End TN REFR Caliper

Atrial Sensed Atrial Paced Ventricular Sensed Ventricular Paced Sensed (Single Chamber) Paced (Single Chamber) Hysteresis Rate PVC after Refractory During Refractory Sensor Rate Smoothing Up Rate Smoothing Down Inserted after AFR Trigger Mode Sense Amp Noise During A-Tachy Response Atrial Tracked at MTR PVARP after PVC PMT Detection and PVARP Threshold New Parameters Active A-Tachy Sense Count Up A-Tachy Sense Count Down Fallback Started Onset Started Fallback Ended Noise Indication Refractory Interval Screen Caliper Location End of Report

AP

(AS) VP

AP

(AS) VP

AP

(AS) VP

AP

(AS) VP

(AS)

AP

VP

event markers with or without electrograms. Markers may be stored using a patient trigger (e.g., magnet application),28 a simple battery-operated radiofrequency transmitter, or on spontaneous activation of predefined algorithms or sequences of sensed or paced events. ELECTROGRAM TELEMETRY The clinician evaluates a pacing system based on an analysis of the electrocardiogram (ECG), but the pacemaker does not respond to P waves or QRS complexes. The latter are surface manifestations of the atrial and ventricular depolarizations. The recorded signal that enters the pacemaker’s sense amplifier by way of the electrode located within or on the heart is termed an electrogram or intracardiac electrogram (EGM). The EGM is composed of a number of elements. The portion that is sensed by the pacemaker is termed the intrinsic deflection; it reflects the rapid deflection that occurs when the wave of electrical cardiac depolarization passes by the electrode. The intrinsic deflection can be characterized by both amplitude and slew rate. The change in voltage amplitude divided

AP

Figure 29-8  ECG and EGM tracings with event marker legend. Lower ECG rhythm strip (top) with simultaneously recorded atrial (AEGM, middle) and ventricular (bottom) electrograms. Labels across bottom identify specific events reflecting the behavior of this Boston Scientific pacemaker. In these tracings, the atrial refractory sensed events (AS) are caused by far-field R-wave sensing that is also visible on the AEGM channel.

by the time duration of this portion of the signal is known as the slew rate, measured in volts per second. Most implanted pacemakers require a slew rate of more than 0.5 V/sec for proper sensing. The other portions of the cardiac depolarization, as reflected by the EGM, are termed the extrinsic deflection. Although the extrinsic deflection may have adequate amplitude, the slew rate is usually too low, precluding this portion of the cardiac signal from being sensed by the pacemaker. At implantation, the amplitude of the EGM is usually measured with a pacing system analyzer (PSA) that reports a millivoltage amplitude. The PSA uses its own unique set of filters, which frequently is not identical to those in the pacemaker’s sense amplifier. Therefore, the reported PSA signal, at best, provides an approximation of what the pacemaker effectively sees. Newer pacing system analyzers are now being introduced that will allow adjustment of the filters to match specific models of pacemakers and ICDs to eliminate this discrepancy. Likewise, the morphology of the EGM observed on a high-fidelity monitor is not identical to the signal as seen by the pacemaker, because filters in the pacemaker’s sense amplifier usually have a narrower bandpass and therefore block out some of the frequencies (Fig. 29-10).



29  Pacemaker Troubleshooting and Follow-up

Mode Rate Minimum Maximum RRF Auto A-V Delay Program Current

DDDR + MV 60 ppm 130 ppm 23 Normal

VMR 114 ppm 130 ppm

AMS 114 ppm 130 ppm

(140–100 ms) (#171, 5 May 93)

Longevity > Cell Impedance Magnet Rate

853

50 months 650  90 ppm

Measured RRF Rate Sense Pace

Events Pace A Sense DDDR Noise V Lead I Gain 20 mm/mV Speed 25 mm/s

Telectronics

9600 v4. 1 OUE

Pacing Systems

Figure 29-9  Laddergram from rate-modulated dual-chamber pacing system. The event markers are identified by a variety of symbols displayed in a key to the left of the tracing. In addition, battery (cell) impedance and projected longevity are reported in the upper right portion of the tracing, and selected programmed parameters are shown in the upper left quadrant. AV, Atrioventricular; RRF, rate response factor. Data from a META DDDR Model 1250 Telectronics Pacing Systems, now Pacesetter, St. Jude Medical CRMD, Sylmar, Calif.), displayed with a Model 9600 programmer.

Examining the EGM recorded with a physiologic recorder or telemetry with a wide band-pass can provide valuable information on the slew rate, splintering of the intrinsic deflection, and other morphologic abnormalities. Measurements of the peak-to-peak amplitude of the EGM, as recorded at implantation or as telemetered from an already-implanted pacemaker, are typically used to determine the sensing threshold. This approach may be inappropriate if the frequency content of the signal is outside the constraints of the band-pass filter of the sense amplifier.

If the clinician wants to determine the sensing threshold for a given patient, the sensitivity of the system should be progressively reduced until the system no longer consistently senses the native signal. The least sensitive setting (usually identified by millivolt amplitude) at which there is consistent sensing is the sensing threshold. The precision of this measurement is limited by the number and range of programmable sensitivity options in the specific model of pacemaker.29-31 All modern pacing systems now have the ability automatically to measure the EGM amplitude and report this to the clinician. This measurement

ECG Controls

ECG Controls

Surface ECG ................................... On Position ........................................... 1 Gain ................................................ 1 Filter ............................................ Off Markers ........................................... On Position .......................................... 2 IEGM ............................................... On Position .......................................... 3 Gain ............................................... 5 Configuration .................... Vtip-Vring Sweep Speed ................................. 100 1/4 Second

mV/cm

mV/cm mm/s

Surface ECG ................................... On Position ........................................... 1 Gain ................................................ 1 Filter ............................................ Off Markers ........................................... On Position .......................................... 2 IEGM ............................................... On Position .......................................... 3 Gain ............................................... 5 Configuration .............. V Sense Amp Sweep Speed ................................. 100

mV/cm mm/s

1/4 Second

P 124

P R

134

501 633

Vtip-Vring

mV/cm

R 804 929

V Sense Amp

Figure 29-10  Side-by-side display of telemetered bipolar ventricular electrograms. Before processing by the sense amplifier (Vtip-Vring) on the left and after being processed by the sense amplifier (V Sense Amp) on the right. The simultaneously recorded surface ECG and telemetered event markers are also shown (P, native atrial depolarization; R, native ventricular depolarization), with the horizontal lines representing the atrial (top) and ventricular (bottom) refractory periods. The circuitry of the sense amplifier has a narrow band-pass filter that modifies the raw signal, which can also be telemetered. These signals were telemetered from a Pacesetter Affinity DR pacemaker, Model 5330 (St. Jude Medical CRMD, Sylmar, Calif).

854

SECTION 4  Follow-up and Programming

ECG LEAD II 0.05 mV/mm

A EGM 0.2 mV/mm 0.1 mV/mm

Marker Channel A S

V S

V S

V S

A S

V S

A R

V P

V S

A S

V S

A R

A S

V S

A R

V P

AA SR

V P

V S

V S

V S

V S

V S

Figure 29-11  Dual-chamber pulse generator tracings. Simultaneous surface ECG (top), atrial electrogram (AEGM; middle), and event markers (bottom) (Medtronic). Although the “automatic mode switch” algorithm was enabled, this system did not switch modes despite the persistence of atrial fibrillation (AF); the reason is clearly identified from the AEGMs, which were telemetered before being processed by the sense amplifier. The AF signal is a predominantly low-frequency signal identified by the slow-rise deflections, even though the peak-to-peak amplitude was well above the programmed sensitivity and should have been adequate for AF to be sensed. These low-frequency signals were filtered out by the sense amplifier, as demonstrated by the event markers—very few of the fibrillatory signals are sensed (AS or AR); thus the rhythm never fulfills the rate criteria necessary to initiate mode switching. Note that the signals with a discrete rapid deflection (arrows) were properly sensed, whereas those that were not sensed had relatively slow deflections.

is done through the pacemaker’s band-pass filter and therefore is a good estimation of the EGM size. The limitation to this method occurs when there is a large beat-to-beat or respiratory variation of the EGM size. The best method available uses this automatic measurement together with a beat-by-beat digital readout of the EGM amplitude. With this approach, the range of actual EGMs can be accurately evaluated. Unfortunately, this method of measurement is not widely available. Other EGMs are obtained after the signal is processed by the pacemaker’s sense amplifier. As shown in Figure 29-10, both filtered and unfiltered EGMs may be available. Although the unfiltered telemetered EGM should not be used to determine the sensing threshold, it has many other roles.32,33 A primary value is in identifying signals that are being sensed but are not visible on the surface ECG. Another role is to facilitate analysis of the timing of the pacing system, because the sensed intrinsic deflection resets one or more timers. The intrinsic deflection at which sensing occurs can best be identified from the EGM; it is only indirectly measured from the surface ECG. In many cases, the telemetered EGM may be used to confirm capture (particularly atrial) when the evoked complex (P-wave or QRS) is not visible in any lead of the surface ECG.34,35 The evoked EGM may be enhanced by using a unique output pulse configuration to help cancel the residual polarization artifact, or by recording the signal through electrodes not directly involved with the output pulse. The output pulse tends to overload the telemetry or sense amplifier, driving the signal off scale. This is followed by a refractory period within the telemetry amplifier before anything can again be recognized. However, many of the newer pacing systems have more advanced telemetry systems that are able to blank the output pulse and quickly recover to provide high-quality EGM signals. The telemetered EGM has been effectively used to diagnose native arrhythmias, in which the pacemaker is simply an innocent bystander, or to identify retrograde P waves not visible on the surface ECG. The latter ability may facilitate programming of the PVARP to prevent pacemaker-mediated tachycardia.35-43 The telemetered EGM provides clues to why episodes of undersensing may be occurring, including splintering of the EGM and low slew rates, which may place the signal outside the tight constraints of the pacemaker’s sense amplifier, despite an adequate peak-to-peak amplitude44 (Fig. 29-11). The telemetered EGM can also be monitored periodically to follow the progression of the patient’s intrinsic disease process. A decrease in the amplitude of the telemetered EGM was reported to identify early

rejection effectively in cardiac transplantation recipients; a return to the baseline amplitude correlated with resolution of the rejection process.45 Preliminary work on the signal-averaged EGM, either atrial or ventricular, suggests that it may be helpful in identifying disease in the respective chamber that is beyond the resolution of signal-averaging the surface ECG.46 Limitations of Electrogram Telemetry The apparently adequate amplitude of the telemetered EGM for sensing does not mean that the pacemaker will sense it. The telemetry amplifier may use filters different from those in the sensing circuit, providing qualitative rather than quantitative data on the EGM (see Fig. 29-11). In most pacing systems, telemetered EGMs also have limitations similar to those of event markers. EGMs are real-time recordings and cannot be retrospectively provided by the programmer to facilitate the interpretation of an earlier ECG. Real-time telemetry allows the physician to analyze the behavior of the pacing system when the patient is in the physician’s office or clinic while these diagnostics are being accessed with the programmer. This is impractical over a long period. In addition, it does not allow the patient to move around much while these recordings are being obtained. Long-term monitoring of pacing system behavior requires a Holter monitor, a loop memory recorder, or event counter telemetry, depending on the desired degree of precision. Pacemakers with microprocessors and significant random access memory (RAM) can now store select EGMs,47,48 as well as event markers, when triggered by the patient or by a predefined set of circumstances. This may greatly reduce the need for Holter or other monitoring techniques to evaluate intermittent symptoms in patients with pacemakers. EVENT COUNTER TELEMETRY In simple terms, the pacemaker “knows” when it has released an output pulse or responded to a sensed event. The availability of high-density, low-power RAM and read-only memory (ROM) integral to microprocessors that can be incorporated in the pacemaker has given pacemakers the ability to store information about system performance for retrieval at a later date. The objective of the event counters is to facilitate the clinician’s ability to analyze and manage the patient’s pacing therapy more effectively. Although this may lengthen the evaluation, to retrieve and interpret these data, the



additional time is usually minimal. This technology can provide the clinician with information that is crucial to understanding the performance of the system over time, and consequently to directing the programming of the system and achieving optimal performance. Other techniques, such as standard Holter monitor recordings or repeated exercise tolerance tests, although valuable, are impractical, arduous, and relatively expensive to acquire on a routine or repeated basis. The first use of stored diagnostic data in cardiac pacemakers was associated with the introduction of multiparameter programmability. Simple data using codes to identify implant indications and medications could be downloaded into the pacemaker for retrieval at subsequent follow-up evaluations. This ability has been expanded, allowing entry of free text (date of implantation, lead model numbers, pharmacologic regimens, and acute implant measurements, including capture and sensing thresholds and lead impedances; see Fig. 29-1, B). This information is printed with the programmed parameters each time the pacemaker is interrogated. A variety of diagnostic event counters are now available, too numerous to detail in this chapter. Some provide information on the overall performance of the system, whereas others focus on a specific algorithm or subsystem. Still others provide detailed information on the basis of the time course of events. Select examples are used to illustrate these capabilities. Total System Performance Counters The simplest systems keep track of the number of times a pacing stimulus is released or a native complex is sensed. This allows for an assessment of the degree to which the pacemaker was used by calculating the percent pacing in each chamber. A refinement of this ability allows the pacemaker to diagnose bradycardia and, in the dual-chamber modes, to determine whether the bradycardia was the result of sinus node dysfunction or AV block. Event counters with this ability have also been termed diagnostic data, implanted Holter systems, and data logging.49-55 With the introduction of dual-chamber pacing (specifically the DDD mode), the potential interactions between the pacemaker and the patient increased from two (pacing or sensing in one chamber) to five (pacing or sensing in the atria or ventricles and sensing ventricular activity without preexisting atrial activity). The situation became even more complex with the introduction of multiple-site ventricular and atrial pacing configurations. Knowledge of how the pacing system has behaved over time, combined with the clinician’s knowledge of the patient, provides invaluable information toward assessing the overall performance of the implanted system. The various annotations described in the event marker section were combined to provide a cryptic description of the different operational states of the DDD mode. These include an atrial sensed event followed by a ventricular sensed event (AS-VS or PR), indicating that the pacemaker is inhibited on both channels. Atrial sensing followed by a ventricular paced event (AS-VP or PV) refers to P-wave synchronous ventricular pacing. Atrial pacing with intact AV nodal conduction or functional single-chamber atrial pacing is indicated by AP-VS or AR. Base-rate pacing in both chambers is represented by AP-VP or AV. A ventricular sensed event not preceded by atrial activity, either paced or sensed, is a premature ventricular event (PVE), identified by the letter R or the combination VS. Some systems label these events premature ventricular contractions, or complexes (PVCs). This information may be collected in conjunction with events occurring in specific rate bins, allowing for a detailed report of heart rate distributions. Additional data collected include the percentage of pacing in the atrium and ventricle, length of time at the maximum tracking rate, and the number of episodes in which the pacing system reached the programmed upper rate limit (Fig. 29-12). Additional data may be recorded regarding mode-switching events, pacemakermediated tachycardia (PMT) termination algorithm use, or the number of times any one of several other special features was activated. The counters are able to continue to accumulate data until one of the

29  Pacemaker Troubleshooting and Follow-up

855

pacing state bins is full and cannot accept additional information. At this point, one or more of the counters are frozen. The volume of data that can be stored depends on the memory capacity of the pacemaker that is dedicated to these features. The following example illustrates the amount of data that can be stored, or the quantity of memory. All data are stored in a binary code, represented by a series of 1s and 0s. A binary unit of memory is called a bit. Eight bits are a byte and result in 256 combinations of 1s and 0s. If each series of combinations represents a single item of data, a total of 256 pieces of information can be stored in a system with eight bits of memory. As the number of bits increases, the amount of data that can be stored increases exponentially. If each pacing state is represented by a single combination of bits, and there are 24 bits in the RAM devoted to these counters, more than 17 million events can be counted and stored in memory for retrieval at the time of routine pacing system follow-up. Reading the counters requires access to the memory banks in the pacemaker through the use of specific coded commands from the programmer. One DDD system introduced in the mid-1980s had sufficient memory to provide a summary of pacing system behavior for a period of about 6 months. As memory capacity has increased and data compression algorithms have evolved, these systems are now able to store much more data for periods longer than 1 year. Storing a simple marker of the pacing state and rate requires relatively little memory compared with storing waveform data representing the rhythm, as depicted by a consecutive series of EGMs. A theoretical 100-Hz bandwidth with 200 samples per cardiac cycle at eight bits of resolution per sample, recording the entire rhythm during a 24-hour period, would require 140,000,000 bits/day, even if the heart rate was a steady 60 beats per minute (bpm).47 Most implantable defibrillator systems store a series of EGMs preceding and following the delivery of antitachycardia therapy. Premium pacing systems use certain triggers to initiate EGM storage. These triggers may be a high atrial or a high ventricular rate, initiation of mode switching, or activation of any of several other specialized algorithms. Storage may also be triggered by application of the magnet or use of a simple transmitter device by the patient when symptoms are present. An early method to save memory was to provide “snapshots” of representative complexes; the trigger to store these data in an ICD was delivery of antitachycardia therapy. Extensive storage of cardiac rhythm data within pacemakers became possible with increasingly sophisticated data compression algorithms and more memory than previously available. Higher-bandwidth data transmission channels are required for this volume of data storage, particularly for long series of rhythms, so that transmission can be accomplished as efficiently and as quickly as possible. Implanted looping memory event recorder (implantable loop recorder, ILR) capability, complete with stored rhythms, is now available as a stand-alone device, in ICDs, and in high-end pacemakers. Most of the older pacemakers, however, continue to store only data reflecting the total number of times a pacing state was encountered and, in some systems, the distribution of rates or intervals, rate ranges, or mean rates within these pacing states. This information provides the physician with an overview of the function of the system in the patient. Predominant base-rate pacing is expected in patients with marked sinus node dysfunction and in those receiving certain medications such as beta-adrenergic blockers or some calcium channel blockers. On the other hand, predominant base-rate pacing (AP-VP) in patients whose primary indication for pacing was complete heart block suggests either the development of sinus node dysfunction or primary atrial undersensing. In these same patients with high-grade AV block, frequent counts of AS-VS and PVEs, particularly in the absence of known ventricular ectopy, suggests episodes of ventricular oversensing or resolution of the AV block. Large numbers of counts regarding PMTs warrant a reassessment of retrograde conduction and possible adjustment of the programmed PVARP or PMT prevention and termination algorithm. It may also mean only that the maximum tracking rate (MTR) is

SECTION 4  Follow-up and Programming

HEART RATE HISTOGRAM Time at max track rate Max sensor Max track

Base

A Tach detection Paced (AP-VP, AP-VS) Sensed (AP-VP, AP-VS) PVC Sensor-indicated rate

Time (%)

100

30

50

70

90

EVENTS AP counts VP counts AV conduction counts



170

AS-VP AS-VS AP-VP AP-VS Minutes

AMS base

100

Hours

Time (%)

Episodes

100

V Rates during AMS 100

AS

PVC 175

bpm 0d 9h 20m 34s in AMS since last session

Figure 29-12  Heart rate, event, and mode switch histograms. Data represent the performance of the pacing system over the preceding 448 days, with monitoring of every event. Patient had a St. Jude Medical device programmed to DDDR mode. The event histogram is a graphic display of the relative percentage of events within each of the five basic pacing states, whereas the heart rate histogram is a graphic display of the rate distribution based on atrial sensed or atrial paced events. This distribution reflects normal chronotropic function of the sinus node in this patient, whose pacemaker was placed for intermittent atrioventricular block (almost all the atrial paced events are at the base rate). The percentage of time per rate bin represents a normalized display of the relative percentage of atrial paced or atrial sensed events and premature ventricular sensed events in each rate bin during this period. The AMS summary and V Rates During AMS indicate the atrial rates during mode switch, the duration of the mode switch events, and the ventricular response during the mode switch events. These data can be used to manage antiarrhythmia medication as well as AV node–slowing medications.

being reached, as some devices use the MTR as the trigger for PMT intervention. A large number of counts at the MTR suggests that the upper rate limit should be reassessed, because it may be too low for the patient’s physiologic needs. It might also indicate pathologic atrial rhythms. Event counter telemetry can help reveal the overall function of the pacing system; a variation from the clinician’s knowledge of the patient may suggest the need for a further evaluation. When the additional ability to monitor a series of rates and pacing states is added, chronotropic function can be assessed by the distribution of atrial sensed rates (AS-VS or PR and AS-VP or PV; see Fig. 29-12). Furthermore, atrial pacing at rates above the programmed base rate reflects sensor drive in the DDDR pacing systems, providing an overview of the sensor behavior. The ability to report both rates and pacing states can provide the clinician with a better insight into the cause of PVEs as well as overall pacing system function. True premature ventricular contractions tend to occur at short coupling intervals, which is equivalent to a rapid rate. Large numbers of PVEs might suggest recurrent ventricular arrhythmias.56,57 If there are large numbers of PVE counts at relatively low rates, the clinician should consider episodes of atrial undersensing or accelerated junctional rhythms, which would also fulfill the pacemaker’s criteria for a PVE (i.e., a sensed R wave not preceded by an atrial event). Subsystem Performance Counters An increasing number of specific algorithms and capabilities are used either intermittently or potentially independently of the functional performance of the pacing system. An early counter representative of

this capability is the sensor-indicated rate histogram, which reports the distribution of pacing rates that would have occurred had the sensor been totally controlling the pacing rates.58,59 This counter reports the sensor-defined rates, even if the pacemaker was inhibited by a faster native rhythm or the actual functional rate was being controlled by the sensed atrial activity (Fig. 29-13). Other subsystem performance counters include automatic mode switch histograms, reports of the cumulative length of time for which the system functioned at MTR, number of times the PMT algorithm was enabled, high atrial or ventricular rate episodes (Fig. 29-14), and sudden rate-drop episodes. These diagnostic counters provide detailed information about the use of a specific algorithm or system behavior that is not activated daily or is not visible on the ECG, making identification difficult using standard recording techniques such as a Holter monitor. The principal limitation associated with the two types of counters so far described is that counts are placed in a bin, either the pacing state alone or the pacing state and rate, which provides a onedimensional view of the system’s behavior. If the period of monitoring is short, as during a casual or brisk walk, the clinician can reasonably assess the behavior of the pacing system. Longer periods of monitoring accumulate and overlap the results of many activities. This precludes an assessment of the pacing system’s behavior during a specific activity, or the identification of a symptomatic episode occurring at an earlier time. The ability of the system to store pacing state and rate data with respect to time (i.e., time-based event counters) has been variably termed event record or pacemaker Holter systems.60-62 Technically, this is not yet a true Holter monitor, because continuous rhythm



29  Pacemaker Troubleshooting and Follow-up HEART RATE HISTOGRAM Time at max track rate



bpm HEART RATE HISTOGRAM Time at max track rate

Max sensor Max track

Base

100

0% A Tach detection Paced (AP-VP, AP-VS) Sensed (AP-VP, AP-VS) PVC Sensor-indicated rate

Time (%)

Figure 29-13  Sensor-indicated rate histograms show­ ing heart rates for two patients. The bars show the actual heart rates and are dark if atrial paced or white if atrial sensed (St. Jude Medical pacemaker). The open circles indicate what the activity sensor would have driven the heart rate to if the sensor-indicated rate was faster than the patient’s intrinsic heart rate. A, This histogram is from a patient with a normal sinoatrial (SA) node, showing that the patient’s heart rate exceeded the sensor-indicated rate in all bins except the base rate bin. B, This histogram is from a patient with sinus node incompetence; thus almost all the atrial events are paced, and at the sensor-indicated rate.

857

30

50

70

90

110

B

130

150

170

190 200 225 255 >

bpm

High rate epis-A. Tachy rate (ppm)

Detection rate–180 ppm

*EGM collected >400 202 >400 365 335 >400 >400

Feb 02 06:42 *Feb 01 18:45 Feb 01 11:37 Jan 29 08:38 Jan 28 17:25 Jan 27 01:28 Jan 23 17:34 120 80 Seconds

0

180

Rate (ppm)

High rate epis–A. data >300 250 200 510 100 50

DR

–4 –2 0 Sensed event

2

10 10 14 16 18 20 22 24 Beats

Paced event

A. EGM 2.370 Seconds of EGM Figure 29-14  High-rate episodes on AEGM. High-rate episode summary (top) and high-rate episode graphic with stored atrial electrogram (AEGM; bottom). These data facilitate the clinician’s ability to assess the behavior of the pacing system between office visits. In this case, the specific episode associated with the AEGM reported atrial paced events occurring above the trigger level for this event counter, which was also above the maximum sensor rate. The electrogram demonstrates atrial pacing with a large, far-field R-paced ventricular event; presumably the labeled high-rate episode was caused by far-field sensing. This knowledge may be helpful in further programming of the pacemaker. Data from Medtronic Thera DR Model 7940.

858

SECTION 4  Follow-up and Programming

recordings are not retained in memory, even though rate data may be available. Time-Based System Performance Counters Time-based event counters require an extensive amount of memory. Not only are the pacing state and rate stored, but these data must be stored with respect to preceding and subsequent events. The data cannot be simply dumped into a rate or pacing state bin. Each piece of data (i.e., every cardiac event) must have a time reference, which takes significantly more memory than simple histogram-type counters. Two techniques are available for storing real-time data. One is to continue to accumulate the data until the memory is full and then to freeze the recorded events. Freezing all the counters at the same time maintains the ratios between the events. A clearing function is usually provided to reset the counters. In some devices, reprogramming of any parameter or specific parameters (e.g., rate or pacing mode) can result in the automatic clearing of these data. This “initial events” or “frozen” recording technique is especially useful for short-term monitoring, as in office-based exercise evaluations. It also allows the system’s response to exercise to be evaluated, often without the need for simultaneous ECG monitoring. The other option is to collect the data continuously. As the counters fill, new data are added at the expense of the oldest data (Fig. 29-15). This has been called rolling trend, final trend, or continuous data storage and is based on the “first in, first out” (FIFO) principle. When the patient is seen in follow-up, the data acquired over the time immediately preceding the interrogation of the system are available for review. The patient can often recall symptoms and activities during this period. These can be correlated with the behavior of the pacing system at the time of the symptoms. In this manner, the clinical staff caring for the patient may further assess chronotropic function, the behavior of the pacemaker during a variety of special or usual activities, and whether the sensor and other algorithms are behaving appropriately. The clinician may gain insight into the cause of palpitations and other symptoms that may have occurred during this time by correlation of the recorded data and the patient’s complaints or activities.51,58-62 Sensor-input data have been combined with the actual rates achieved to facilitate reprogramming of the sensor parameters. Once acquired, the data from an exercise session are retained in the memory of the programmer, uploaded to the programmer, and then displayed on a screen. The system’s performance is based on a given set of sensor parameters that were in effect at that time. Because the pacemaker has the actual sensor-signal data, it can calculate how the unit would perform in response to a different set of sensor parameters. If a new set of sensor parameters is entered into the programmer, the curves that were based on the original input data are redrawn to display the system’s projected behavior in response to the new set of parameters. The clinical staff can then determine the best sensor parameters for the individual patient without having the patient perform repeated activities (Fig. 29-16). This feature has been termed redraw,63 exercise test, or prediction model.64 Limitations of Event Counter Telemetry The major value of event counters is providing a review of system performance over time. This is not available from the real-time diagnostic features of measured data and event counter and EGM telemetry. The data, however, are interpretable only after a detailed assessment of the capture and sensing thresholds, in a manner analogous to event marker telemetry. The pacemaker can only store information that it knows about: output and sensed events, sensor data, and activation of unique algorithms. If there is a problem with undersensing, the pacemaker releases a pacing pulse, and the counters report a paced rhythm. Similarly, a large number of sensed events may cause the pacemaker to be inhibited on the respective channel. The counter simply reports a large percentage of sensed events, but this may be clinically inappropriate if the cause is oversensing. With respect to pacing, a rhythm that is predominantly composed of AV- or PV-paced complexes does not necessarily indicate complete

heart block. It might result from a programmed AV delay that was not sufficiently long to allow for full conduction through the AV node. Although the ventricular complex could have been fully paced, it could also have been a fusion or pseudofusion beat. The counters cannot differentiate between these complexes, because the native complex had not yet been sensed, the timer had been completed, and an output was delivered. Another situation would be a total loss of ventricular capture with intact AV nodal conduction (Fig. 29-17). The first conducted R wave in this figure would not have been sensed, because it occurred during the refractory period that followed the ventricular output pulse. An identical result in the counters would occur with intact AV nodal conduction but with ventricular undersensing. The event counters simply report the system’s performance without making any statement or judgment about the appropriateness of this behavior. The information provided by the event counters can be interpreted only after the programmed parameters are known, the pacing and sensing thresholds have been determined, and the status of the native rhythm is known. If the pacemaker is programmed to provide a good margin of safety for both pacing and sensing, the event counters are likely to be an accurate reflection of the patient’s clinical rhythms. These data also provide insight into the degree to which the patient requires pacing support at the current programmed parameters, the chronotropic function of the sinus node, and responsiveness of the sensor. Evidence of oversensing or lead dysfunction renders the event counter data suspect with regard to these findings, although a marked change in event counter data can provide the clinician with a clue to a developing problem. The event counter data cannot be adequately interpreted without knowledge of how these data are collected, the clinical status of the patient, and any unique behavioral performance of the implanted pacemaker. This is illustrated by Figure 29-14, which is an atrial highrate graphic from a Medtronic Thera DR pacemaker. The reported rates were greater than 200 bpm, yet the graphic suggests that these were atrial paced events and that the device is not capable of being programmed to rates this high. It is essential to know how the manufacturer calculates rates. In this case, the device measures the interval between atrial events; if the event preceding the atrial output occurred during the refractory period (labeled AR by the markers), the reported atrial paced rate would be based on the AR-AP interval. With this knowledge, the graphic report can be understood. If this fact were not known, the graphic would suggest a pacing system malfunction. Atrial fibrillation (AF) is a major clinical problem that is common in patients with cardiac implantable electronic devices (CIEDs). Management can be improved by knowing whether AF is present, the frequency of AF, and the duration of AF episodes. Knowing these data allows the clinician to determine the need for antiarrhythmia therapy, for ventricular rate–slowing medication or interventions, or for anticoagulation. Several diagnostic counters are available to assist in the management of AF (Fig. 29-18). These may consist of the number and duration of the episodes, atrial rates and ventricular rates during the episodes, and specific dates and times so that patient symptoms can be correlated to events. The one caution in terms of accepting data from these counters is the possibility of oversensing in the atrial channel, which would cause inappropriate assignment of events to these diagnostics. The most common cause of false information is sensing of the far-field QRS complex by the atrial lead (Fig. 29-19). This leads to double-counting of the heart rate and incorrect classification of the event as atrial high rate. Use of stored EGMs to verify the cause of the high-rate episode is advised whenever possible, to avoid inappropriate treatment for nonexistent AF.

Pacing System Malfunction Interrogating the pacemaker about programmed parameters and measured data, retrieval of any and all event count data, and the use of the event markers and EGM telemetry capabilities are essential in a routine office-based follow-up evaluation. It is even more important when



29  Pacemaker Troubleshooting and Follow-up

859

Legend A =AV

P =PV

=PVE

A=AR

Time Scale

P=PR

S =Paced

S=Sensed V =Vent Paced

60 h

O=Off

D D D

190

Rate (ppm)

170 150 130 110 90 70 50 30 9:33:17 am

9:33:17 pm

9:33:17 am

9:33:17 pm

Time

Event Bar Graph

Event Time Graph 100% Time 91

Time (%)

PV PR AV

9

0 PV

PR

0 AV

AR

0 PVE

AR

PVE 6:33:17 am 2:03:17 am 11:03:17 pm 9:33:17 pm 3:33:17 pm 12:33:17 pm 9:33:17 am

Rate Bar Graph

Rate Time Graph

18

18

11 1 1 1 0

45

65

85

Atrial Sensed Atrial Paced

0

105 125 Rate (ppm)

0

0

145

0

0

165

0 185

Rate (ppm)

Time (%)

52

185 165 145 125 105 85 65 45

100% Time

6:33:17 am 2:03:17 am 11:03:17 pm 3:33:17 pm 9:33:17 pm 12:33:17 pm 9:33:17 am

Figure 29-15  Event record display. The sampling interval was 26 seconds, which provides a detailed overview of the behavior of the pacing system for the preceding 60 hours. The top display is an overview of the moment-to-moment behavior of the pacing system, with the vertical lines representing the maximum and minimum rates during each time period (the total displayed interval is divided into 40 equal time segments) and with the cross-bar representing the mean heart rate. The vertical line is displayed if there are two or more complexes in the specific time bin. The display scale can be expanded to display individual events, in which case a specific alphanumeric label is shown, consistent with the legend in  the upper left. The same data may be displayed as an event bar graph (equivalent to the event histogram) or as a rate bar graph (equivalent to the heart rate histogram). The solid bars represent atrial paced events; thus atrial rates greater than the programmed base rate represent sensor drive. Atrial rates lower than the programmed base rate represent “sleep mode” behavior that was also programmed. The time graphs automatically divide the overall monitoring period into six equal segments. Display is from a Pacesetter Trilogy DR+ Model 2364 (St. Jude Medical).

860

SECTION 4  Follow-up and Programming

RATE RESPONSE OPTIMIZATION Rate response model

Parameters

190 150

Rate (bpm)

Sensor Max sensor rate Threshold (Measured avg) Slope (Measured auto) Reation time Recovery time

Modeled Tested Intrinsic

110 70

Tested On 120 bpm Auto (–0.5) Auto (+3) Very fast Medium

Modeled On 120 bpm Auto (–0.5) A 2.0 16 n/a Very fast Medium

30 0

1

2

4

3

5

Exercise duration (min) Figure 29-16  Exercise test report. The lower line on the graph represents the actual behavior of the pacing system during a hall walk with the settings as noted to the right of the graph as “tested.” Patient has St. Jude Verity pacemaker. The thicker line above represents the behavior of the pacemaker under sensor drive at the proposed or “modeled” values. By using this type of feature, the patient only needs to take a single walk to set up the activity response of the device. Mode: DDDR

Rate: 50 ppm A-V Delay: 175 msec Magnet: TEMPORARY OFF ECG/IEGM PARAMETERS

Surface ECG Surface ECG Gain Surface ECG Filter Intracardiac EGM Intracardiac EGM Gain Chart Speed

ON 1.0 mv/div ON OFF 2.5 mv/div 25.0 mm/sec

evaluating a suspected pacing system malfunction. Knowledge of the present programmed settings, combined with the baseline data with which the current results can be compared, is crucial. Many devices have special programming features and idiosyncrasies that may appear to be malfunctions to clinicians who are not completely familiar with the particular system under scrutiny. It is not unusual to hear about devices being explanted and returned to the manufacturer for failure to pace at the programmed rate, only to find that hysteresis had been enabled. This is only one of many examples of “pseudomalfunctions,” as discussed later.65-69 HISTORICAL CLUES

1.0V P

P

P

V 150

V 147 690 837

V 150

P R

365 350 485

V 122

R

The first step in the evaluation of the patient with a suspected pacing system problem is to gather as much information about the patient as possible (Box 29-1). This includes the indications for the pacemaker, the operative record of the implantation, the model, and possibly the serial numbers of all portions of the implanted pacing system. In addition, one must obtain the current programmed parameters and all

377 Box 29-1 

PATIENT EVALUATION FOR POTENTIAL PACING SYSTEM MALFUNCTION Surface ECG

1.0 sec Figure 29-17  Telemetry data limitations. Although this printout was obtained during a ventricular capture threshold test, it demonstrates the limitations of some of the telemetry data in the absence of a simultaneously recorded electrocardiogram (ECG). The last two ventricular output pulses were subthreshold, resulting in a loss of capture. The endogenous P wave conducted, but with a marked first-degree atrioventricular (AV) block, placing the R wave outside the ventricular refractory period initiated by the subthreshold ventricular output, allowing it to be sensed. Based on event marker and event counter data, this patient would be interpreted as having frequent premature ventricular events (PVEs) interspersed in a stable atrial sensed, ventricular paced rhythm; however, in actuality, there was a loss of ventricular capture with intact AV nodal conduction. Key programmed and recording parameters are also included with each printout to facilitate interpretation; EGM, Electrogram. Data from Pacesetter Synchrony II Model 2022 dualchamber pacing system (St. Jude Medical CRMD, Sylmar, Calif.)

Know the Patient Cardiac and noncardiac diagnoses Exposure to environmental extremes Exposure to sources of electromagnetic interference Programming changes performed by others Know the Pacemaker Manufacturer Model and serial number Alerts or recalls Current programmed settings Device idiosyncrasies Mode and algorithm idiosyncrasies Know the Leads Manufacturer Model and serial number Alerts or recalls Connector type Polarity Insulation material Fixation mechanism Radiographic appearance



29  Pacemaker Troubleshooting and Follow-up

861

Mode Switch Episodes Date/Time

A. Max Rate

37839 37838 37837 37836 37835 37834 37833 37832 37831 37830 37829 37828 37827 37826 37825 37824 37823 37822 37821 37820

Aug 02, 2005 22:07:37 Aug 02, 2005 00:19:30 Jul 30, 2005 23:57:31 Jul 22, 2005 03:22:54 Jul 21, 2005 23:35:48 Jul 21, 2005 21:50:57 Jul 21, 2005 01:25:17 Jul 20, 2005 06:24:08 Jul 20, 2005 01:26:59 Jul 20, 2005 00:58:06 Jul 19, 2005 05:07:23 Jul 19, 2005 03:04:02 Jul 18, 2005 06:15:20 Jul 18, 2005 04:08:05 Jul 18, 2005 03:57:48 Jul 18, 2005 01:14:07 Jul 18, 2005 01:01:24 Jul 17, 2005 17:24:50 Jul 14, 2005 16:02:06 Jul 14, 2005 00:34:16

(Episode in progress) >400 bpm >400 bpm >400 bpm >400 bpm 400 bpm >400 bpm >400 bpm >400 bpm 375 bpm >400 bpm 400 bpm >400 bpm >400 bpm 400 bpm >400 bpm 400 bpm >400 bpm >400 bpm >400 bpm

Avg peak rate

PEAK FILTERED RATE

B

>300 300 275 250 225 200 175 150 125 100

1 0 1 0 0 0 0 0 0

>300 276-300 251-275 226-250 201-225 176-200 151-175 126-150 100-125

1 0 1 0 0 0 0 0 0

V. Max Rate

Duration

146 bpm 94 bpm 143 bpm 80 bpm Paced 128 bpm 102 bpm 80 bpm Paced 91 bpm Paced 95 bpm Paced Paced Paced Paced 85 bpm 154 bpm 130 bpm

22 hr 48 hr 213 hr 4 hr 2 hr 20 hr 19 hr 5 hr 28 min 20 hr 2 hr 21 hr 2 hr 10 min 3 hr 12 min 8 hr 73 hr 15 hr

MODE SWITCH DURATION

Counts

Duration

A

ID#

>48h 0m 48h 0m 24h 0m 8h 0m 3h 0m 1h 0m 20m 0s 6m 0s 3m 0s 1m 0s 0m 0s

Number of occurrences

0 0 0 0 0 0

1

1

0

0 1 0 0 0 0 0 0 1 0

Number of occurrences

CARDIAC COMPASS REPORT

P = Program I = Interrogate AT/AF total hours/day

0

Counts

>48h 0m 24h 0m-48h m 8h 0m-24h 0m 3h 0m-8h 0m 1h 0m-3h 0m 20m 0s-1h 0m 6m 0s-20m 0s 3m 0s-6m 0s 1m 0s-3m 0s 0m 0s-1m 0s

P

I

24 20 16 12 8 4 0

V. rate during >200 AT/AF (bpm) VF Max/day Avg/day

C

150 100

150 msec), and longer time to LV breakthrough.18 Late activation of the posterior or posterolateral basal left ventricle occurred by wavefront propagation around the line of block using the apical or inferior LV walls. Lateral locations of the line of block are characterized by less prolonged QRSd (150 msec) benefit from near-complete replacement of intrinsic activation with BiV or LV pacing (i.e., short AVDs). Patients with less ventricular conduction delay (QRS 150 ms

25 20 dP/dtmax (%)

15 10 5 0 –5 –10 –15

Type II response QRS 120-150 ms

–20 –20

0

20

40

60

80

100

AV delay (% of IAVi) Figure 31-12  Interaction between atrioventricular delay (AVD), magnitude of LV conduction delay, and acute improvement in contractility during CRT. Mean (±SEM) change in LV dP/dtmax when BiV pacing at various AVDs in patients with QRS duration greater than 150 msec (diamonds) or 120 to 150 msec (triangles). The AVDs tested were fixed percentages of the intrinsic A-V interval (iAVI) determined individually for each patient. Acute hemodynamic responders (type I) demonstrate improvement across a broad range of AVDs, whereas hemodynamic nonresponders (type II) may worsen because of very short AVDs. (Modified from Auricchio A et al: Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 99:2993-3001, 1999.)

2. Improved contractility reduces fMR instantaneously and is quantitatively related to an increase in LV dP/dtmax and transmitral pressure59 (Fig. 31-13). 3. Earlier delivery of the posterior apparatus in isovolumetric systole (Fig. 31-14). 4. Reverse volumetric LV remodeling reduces fMR chronically by reducing LV volumes and sphericity, which reduces tethering forces on the mitral valve. Factors 1 to 3 are acute effects and unrelated to geometrical changes (reverse remodeling). Factors 2 to 4 are the primary determinants of reduction in fMR and are directly related to reduction in ventricular conduction delay. It is not well understood what part of the benefit of CRT is caused by reduction in fMR versus resynchronization of contraction directly, because few studies quantitatively measure regurgitant flow. Improved Heart Rate Profile Ventricular resynchronization favorably modifies autonomic balance, as evidenced by reduced mean heart rate and increased heart rate variability, which correlate with improved functional capacity, reverse remodeling, and reduced mortality.95

Cardiac Resynchronization Therapy Systems HARDWARE SYSTEMS Leads and Electrodes: Non–Independently Programmable Ventricular Polarity Configurations Transvenous and epicardial LV pacing leads may be either unipolar or bipolar, although the former dominates current applications. Multiple ventricular pacing polarity configurations are therefore possible. Because programmed polarity settings are common to both ventricular leads, and the type (bipolar or unipolar) of these leads may not be the same, the following considerations apply. In a dual-bipolar configuration, both lead tips are the active electrodes (cathodes) and the rings are the common (nonstimulating) anode. However, the type of ventricular leads implanted defines the

Pulse Generators Conventional dual-chamber pulse generators or specially designed multisite pacing pulse generators may be used for CRT applications (Fig. 31-17). A conventional dual-chamber pulse generator is well suited for CRT in patients with permanent atrial fibrillation. In this situation, the ventricular port is used for the RV lead and the atrial port is used for the LV lead. This permits programming of independent outputs and ventricular-ventricular timing by manipulation of the AV delay. The programming mode can be either DDD/R or DVI/R (see later). A conventional dual-chamber pulse generator can also be used for atrial-synchronous BiV pacing. The single ventricular output must be divided to provide simultaneous stimulation of the RV and LV (dual cathodal system with parallel outputs). This is achieved with a Y adapter and results in simultaneous RV and LV sensing, which may result in ventricular double-counting and loss of CRT, or pacemaker

1

EROA

LV

↓dP/dt 0.5

0

↓Transmitral pressure gradient (TMP) LA

OFF

Time 1

EROA

↓V wave preserves TMP during latter systole

LV

↑dP/dt 0.5

0

CRT

↑Transmitral pressure gradient (TMP)

LA Time

Shaded area = time EROA threshold) resulting in anodal capture. Bottom, Simultaneous BiV pacing when LV output is 2 V and no anodal capture. Note change in activation sequence. During high-LV-output BiV pacing, anodal capture is indicated by attenuation of monophasic R wave in V1 and loss of R (QS) in V2 (horizontal plane) and attenuation of QS in lead I and aVL (frontal plane). QRS duration is shorter. During lower-output BiV pacing, loss of anodal capture is indicated by dominant QS in I, aVL, and dominant R (V1) and RS (V2). QRS duration is longer.

926

SECTION 4  Follow-up and Programming

performance trends. Trend displays include the maximum and minimum LV capture threshold values for the last 80 weeks along with higher-resolution details for the last 14 days.

An ancillary value is the possibility of overcoming phrenic stimulation when the voltage differential between phrenic nerve capture (higher) and LV capture (lower) is sufficiently differentiated. In this situation, LV output voltage can be automatically “capped” beneath the phrenic nerve capture voltage without compromising LV capture. Provision of long-term threshold behavior as a dedicated diagnostic measure might reduce follow-up time by eliminating the need for in-office real-time determinations, and is particularly useful during remote surveillance. When LVCM is enabled, the device automatically monitors the pacing amplitude threshold at periodic intervals, nominally 01:00 am daily. The minimum amplitude that consistently results in ventricular capture (threshold) is stored and reported. If LVCM is programmed to “adaptive,” LV output voltage is automatically reprogrammed toward a selectable maximum output voltage defined by the desired “maximum amplitude safety margin” and reported. Alternately, if LVCM is programmed to “monitor,” LV output is not adjusted, although data regarding threshold determinations are recorded.

Operating Details.  Unlike automatic RV pacing threshold adjusting algorithms in conventional pacemakers, LVCM does not use the evoked response to determine ventricular capture. Rather, LVCM determines LV capture by recording RV sensed events in response to LV monochamber pacing. This requires timing methods to ascertain whether RV sensed events during monochamber LV pacing are caused by native AV conduction, ventricular premature beats, electromagnetic interference (EMI), or other extraneous conditions. RV sensed events outside the “expected” timing window for native AV conduction, or loss of RV sensing during monochamber LV pacing, is used to indicate loss of LV capture (e.g., threshold voltage). The LVCM operation consists of four stages: (1) ventricular rate and stability check, (2) LV-RV conduction check, (3) AV conduction check, and (4) LV pacing threshold search (LVPTS). The order of these stages is not arbitrary. Ventricular rhythm must be stable (6 4 60

Death (%) 1* — 0.8 0

Lead Fracture (%) 4/1.5† 0.5/0.3§ — —

Lead Dislodgment (%) 1.5 2.3/0.5§ 2.4 1.6

Infection (%) 5/1‡ 0.2 0.7 1.8

Other Pocket Complication (%) — 2 3.5 —

Pneumothorax (%) 1.1 — — 1.1

Perforation (%) 0.4 — — 0.7

Modified from Carlson MD, Wilcoff BL, Maisel WH, et al: Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines. Heart Rhythm 3:1250-1273, 2006. *Death within 30 days; not all device implant related. †Subclavian/cephalic. ‡Abdominal/pectoral. §Subcutaneous/submuscular. PM, Pacemaker.

complications from generator changes.74-77 Depending on the specific indications (e.g., recently implanted drug-eluting coronary stents), the timing of a device replacement may need to be carefully considered.77 Risks of Lead Extraction Although lead extraction has historically been associated with a small but significant mortality risk, improvements in lead extraction technology and increased operator experience challenge the reliability of earlier estimates of morbidity and mortality associated with the procedure. For example, among a retrospective cohort of 348 patients undergoing 349 ICD lead extractions (mean implant duration of 27.5 months) at five high-volume extraction centers between May 2005 and August 2009, complete removal of the index lead was accomplished in every case with no major complications, and minor complications were observed in only 0.57% of patients. Simple traction was used in 49.7% of cases, with additional specialized extraction tools required in the remainder.78 In contrast, registry data from both American and European experiences with 7823 extraction procedures involving 12,833 pacemaker and ICD leads demonstrated a major complication rate of 1.6%.79 These studies identified implant duration of the oldest lead, ICD leads (compared to pacemaker leads), female gender, low-volume extraction hospitals, and the need for laser assistance as risk factors for adverse outcomes.79 Similarly, among 2561 pacemaker and ICD leads in 1684 patients undergoing laser lead extraction in the PLEXES Trial, 1.9% experienced a major complication, with 0.8% in-hospital mortality.80 A study of 2405 laser-assisted lead extractions in 1449 patients resulted in a 97.7% clinical success rate, 1.4% major adverse event rate, 0.28% procedure-related mortality, and 1.86% in-hospital mortality.81 Contemporary registries involving high-volume centers similarly report high procedural success rates and very low rates of serious complications (0.4%-0.9%).82,83 Several studies have demonstrated a significant learning curve associated with lead extraction, particularly for operators with fewer than 20 to 30 cases. Even experienced lead extractors continued to improve with time and volume.84-87 HRS guidelines particularly emphasize the importance of operator experience for procedural success and clinical safety.79 Notably, the favorable complication rates associated with lead extraction, which typically involves both lead removal and device system reimplantation, actually appear better than generator replacement alone. This apparent paradox relates to the terminology used to define major and minor complications; even those complications defined for study purposes as “minor” may be clinically important. The HRS Transvenous Lead Extraction Consensus Document defines minor complications to include: hematoma at implant site requiring reoperation, venous thrombosis of implant veins requiring medical intervention, vascular repair at extraction site, blood loss requiring transfusion, pulmonary embolism not requiring surgical intervention, and hemodynamically significant air embolism.79 Clearly, some of the “minor” events are also clinically relevant.

Review of device-assisted lead extraction adverse events reported to FDA revealed 57 deaths and 48 serious cardiovascular injuries between 1995 and 2008, with almost 40% occurring in the final 2 study years.88 Most alarming was the observation that some extraction injuries cannot be mitigated—even by emergency cardiac surgery. These uncommon but catastrophic events should serve as a reminder to consider carefully other advisory device clinical management options before embarking on an invasive and potentially harmful strategy. Indeed, not all advisory or malfunction leads need be removed. Lead abandonment rather than extraction may be an option for some patients with suitable anatomy. Abandoned leads do not appear to have a clinically important interaction with defibrillation threshold or sensing, and did not lead to increased thromboembolic complications, in a small study of 78 patients.89 This approach has also be proven effective in pediatric patients.90 Conservative Management and Device Reprogramming Health care providers and patients may choose to monitor a device under advisory with a strategy of routine or enhanced surveillance, although this may not be applicable to all advisories and may not prevent serious outcomes in cases where manifestations of malfunction may be sudden and drastic.91 The availability of patient-managed, remote, and home monitoring devices may be particularly important in the early detection of problems in a patient known to be at risk for malfunction. In some cases, automated remote alerts have identified performance concerns before an important clinical adverse event.12 Patients, however, may not be aware of audible device alerts or may not interpret them correctly;92 as such, this approach must be individualized for appropriate patients. In some cases, device programming changes or software upgrades may help mitigate the clinical impact of an advisory or device performance issue. For example, algorithms can reduce the incidence of inappropriate shocks in patients with lead fracture.93,94 Device and Patient Factors Impacting Clinical Decision Making In addition to the general procedural risks previously discussed, other device- and patient-related characteristics that may impact the risk/ benefit balance of a specific management strategy include the observed or projected rates of device failure and the clinical manifestation of malfunction. Generator and lead failure may present suddenly (e.g., sudden, catastrophic short circuit) or gradually (e.g., premature battery depletion), predictably or without warning. In some cases, specific subcategories of devices under an advisory may be identified according to features such as serial numbers or technical factors related to the initial implant. Similarly, each patient’s clinical characteristics and individual risk profile influences the best clinical management strategy for their problematic device (see Box 34-2). For example, pacemaker dependence or past burden of tachyarrhythmia may influence the potential consequences of device malfunction for that patient. Duration since implant may also influence decision making; more recently implanted leads are

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SECTION 4  Follow-up and Programming

Box 34-3 

RECOMMENDATIONS FOR CLINICIANS MANAGING PACEMAKER AND ICD ADVISORIES 1. Conservative noninvasive management with periodic device monitoring (remote or in person, as appropriate) should be strongly considered particularly for: • Patients who are not pacemaker dependent.* • Patients with an ICD for primary prevention of sudden cardiac death who have not required device therapy for a ventricular arrhythmia. • Patients whose operative risk is high or patients who have other significant competing morbidities, even when the risk of device malfunction or patient harm is substantial. 2. Device system revision or replacement should be considered if in the clinician’s judgment: • The risk of malfunction is likely to lead to patient death or serious harm, and • The risk of revision or replacement is believed to be less than the risk of patient harm from the device malfunction. 3. Reprogramming of the pacemaker or ICD should be performed when this can mitigate the risk of an adverse event from a lead malfunction. Data from Maisel WH, Hauser RG, Hammill SC, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines. Heart Rhythm 6:869-885, 2009. *Pacemaker dependence refers to patients who have no hemodynamically stable underlying heart rhythm in the absence of pacing.

generally easier to extract than older leads.79 Patient comorbidities influence clinical decision making as well. A patient’s overall prognosis from either their underlying cardiac pathology, as with advanced heart failure, or other conditions, such as malignancies, chronic obstructive pulmonary disease, or end-stage renal disease, may render device replacement excessively risky or imprudent because of the poor prognosis. In general, noninvasive management of generator or lead advisories is preferable when the risk of malfunction is deemed to be low, particularly for patients who are not pacemaker dependent or who have not manifested clinical arrhythmia. However, device replacement or system revision merits consideration if the risk of malfunction is likely to lead to patient death or serious harm, and if the risk of revision or replacement is believed to be less than the risk of patient harm from generator or lead malfunction (Box 34-3).6

PSYCHOLOGICAL IMPACT OF RECALLS AND ADVISORIES Anxiety, depression, and posttraumatic stress disorder are common diagnoses in cardiac implantable electronic device (CIED) patients in the absence of device advisories.95,96 Clinicians should therefore remain alert to the potential emotional and psychological impact on patients of learning that their permanent device has become subject to an advisory. Investigations of device advisory impact on patients’ psychological well-being have yielded mixed results. One study examining associations between ICD recalls and anxiety, depression, and quality of life (QOL) found that recalls reduced patient trust in the health care system and that more severe recalls (FDA class I vs. class II) decreased QOL.97 However, not all studies have demonstrated an untoward psychological impact. For example, in 86 patients with advisory Medtronic Marquis ICDs, there was no evidence of long-term psychological morbidity.98 Other investigations also demonstrate that QOL and psychological features are similar in patients with advisory ICDs and those with nonadvisory ICDs.99,100 However, some studies suggest that younger patients and those who previously received shocks may be more likely to experience advisory-related anxiety.101 Timely, quality physician communication is critical to maintaining patient trust and reducing patient anxiety.54 Patients who exhibit persistent, significant anxiety benefit from formal counseling.102 Although most patients with advisory devices do not experience significant, long-term anxiety, some patients may experience ongoing psychological impact. In some the clinical management strategy may need to be adjusted to account for and potentially alleviate significant symptoms.5,6

Conclusion Pacemaker and ICD systems are complex, sophisticated technologies that will occasionally malfunction or fail to behave as anticipated. As a result, manufacturers or regulatory authorities occasionally issue product advisories to inform health care providers and patients about underperforming devices. To manage device advisories optimally, health care providers should know the rates and mechanisms of device malfunction, terminology and threshold for activation of device advisories, communication methods of abnormal device performance, and clinical management of device advisories and malfunctions.

REFERENCES 1. Maisel WH: Cardiovascular device development: lessons learned from pacemaker and implantable cardioverter-defibrillator therapy. Am J Ther 12:183-185, 2005. 2. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 303:322-324, 1980. 3. Maisel WH: Safety issues involving medical devices: implications of recent implantable cardioverter-defibrillator malfunctions. JAMA 294:955-958, 2005. 4. Maisel WH, Hauser R: Proceedings of the ICD Lead Performance Conference. Heart Rhythm 5:1331-1338, 2008. 5. Carlson MD, Wilcoff BL, Maisel WH, et al: Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines. Heart Rhythm 3:1250-1273, 2006. 6. Maisel WH, Hauser RG, Hammill SC, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines. Heart Rhythm 6:869-885, 2009. 7. Maisel WH, Sweeney MO, Stevenson WG, et al: Recalls and safety alerts involving pacemakers and implantable cardioverterdefibrillator generators. JAMA 286:793-799, 2001. 8. Song SL: Bilitch Report: performance of implantable cardiac rhythm management devices. Pacing Clin Electrophysiol 17:692708, 1994. 9. Kawanishi DT, Song S, Furman S, et al: Failure rates of leads, pulse generators, and programmers have not diminished over the last 20 years: formal monitoring of performance is still needed. Bilitch Registry and STIMAREC. Pacing Clin Electrophysiol 19:1819-1823, 1996. 10. Maisel WH, Moynahan M, Zuckerman BD, et al: Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA 295:1901-1906, 2006.

11. Maisel WH: Pacemaker and ICD generator reliability: metaanalysis of device registries. JAMA 295:1929-1934, 2006. 12. Maisel WH, Kramer DB: ICD lead performance. Circulation 117:2721-2723, 2008. 13. Biotronik Cardiac Rhythm Management Product Performance Report, January 2010. http://www.biotronik.com/sixcms/ media.php/162/BIOTRONIK%20Product%20Performance%20 Report%20January%202010.pdf. 14. Boston Scientific CRM Product Performance Report 2010, Q2 Summary Edition. http://www.bostonscientific.com/ templatedata/imports/HTML/CRM/Product_Performance_ Resource_Center/report_archives/q2_10_ppr.pdf. 15. Medtronic Cardiac Rhythm Disease Management Product Performance Report 2010, ed 1, issue 62. http://www.medtronic. com/crm/performance/downloads/mdt-prod-performance2010-1-en.pdf. 16. Sorin Group Cardiac Rhythm Management Product Performance Report. November 2009. http://www.sorin-crm.com/ uploads/Media/SorinCRM_PPR-worldwide.pdf. 17. St. Jude Medical Cardiac Rhythm Management Product Per­ formance Report. May 2010. http://www.sjmprofessional.com/ Resources/reference-guides/~/media/Cardiac%20Pro/ Reference%20and%20Resources/Reference%20Guides/ Product_Performance_Report_CRM_May2010.ashx. 18. Maisel WH: Semper Fidelis: consumer protection for patients with implanted medical devices. N Engl J Med 358:985-987, 2008. 19. Danish Pacemaker and ICD Register 2007 Annual Report. Odense, Denmark. http://www.pacemaker.dk. 20. Eckstein J, Koller MT, Zabel M, et al: Necessity for surgical revision of defibrillator leads implanted long-term: causes and management. Circulation 117:2727-2733, 2008.

21. Aass H, Ilvento J: Short and medium time experience with a tined, multilumen steroid eluting defibrillation lead. J Interv Card Electrophysiol 6:81-86, 2002. 22. Kron J, Herre J, Renfroe EG, et al: Lead- and device-related complications in the Antiarrhythmics versus Implantable Defibrillators Trial. Am Heart J 141:92-98, 2001. 23. Dorwarth U, Frey B, Gugas M, et al: Transvenous defibrillation leads: high incidence of failure during long-term follow-up. J Cardiovasc Electrophysiol 14:38-43, 2003. 24. Ellenbogen KA, Wood MA, Shepard RK, et al: Detection and management of an implantable cardioverter defibrillator lead failure: incidence and clinical implications. J Am Coll Cardiol 41:73-80, 2003. 25. Luria D, Glikson M, Brady PA, et al: Predictors and mode of detection of transvenous lead malfunction in implantable defibrillators. Am J Cardiol 87:901-904, 2001. 26. Kleemann T, Becker T, Doenges K, et al: Annual rate of transvenous defibrillation lead defects in implantable cardioverterdefibrillators over a period of >10 years. Circulation 115:24742480, 2007. 27. Kitamura S, Satomi K, Kurita T, et al: Long-term follow-up of transvenous defibrillation leads: high incidence of fracture in coaxial polyurethane lead. Circ J 70:273-277, 2006. 28. Hauser RG, Cannom D, Hayes DL, et al: Long-term structural failure of coaxial polyurethane implantable cardioverter defibrillator leads. Pacing Clin Electrophysiol 25:879-882, 2002. 29. Borleffs CJW, Van Erven L, Van Bommel RJ, et al: Risk of failure of transvenous implantable cardioverterdefibrillator leads. Circ Arrhythm Electrophysiol 2:411-416, 2009.



34  Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories 30. Corbisiero R, Armbruster R: Does size really matter? A comparison of the Riata lead family based on size and its relation to performance. Pacing Clin Electrophysiol 31:722-726, 2008. 31. Koplan BA, Weiner S, Gilligan D, et al: Clinical and electrical performance of expanded polytetrafluoroethylene-covered defibrillator leads in comparison to traditional leads. Pacing Clin Electrophysiol 31:47-55, 2008. 32. Kupper B, Yee R, O’Hara G, et al: Do small (6.6 Fr.) active and passive fixation defibrillation leads perform as well as larger sized leads? A multi-centre analysis. Europace 9:657-661, 2007. 33. Luria D, Bar-Lev D, Gurevitz O, et al: Long-term performance of screw-in atrial pacing leads: a randomized comparison of J-shaped and straight leads. Pacing Clin Electrophysiol 28:898902, 2005. 34. Maisel WH: Transvenous implantable cardioverter leads—the weakest link. Circulation 115:2461-2463, 2007. 35. Maisel WH: Medical device regulation: an introduction for the practicing physician. Ann Intern Med 296-302, 2004. 36. US Food and Drug Administration Center for Devices and Radiological Health Annual Reports. http://www.fda.gov/ AboutFDA/CentersOffices/CDRH/CDRHReports/ucm 109733.htm. 37. Kirkpatrick JN, Ghani SN, Burke MC, Knight BP: Postmortem interrogation and retrieval of implantable pacemakers and defibrillators: a survey of morticians and patients. J Cardiovasc Electrophysiol 18:478-482, 2007. 38. US Food and Drug Administration: MAUDE: Manufacturer and User Facility Device Experience. http://www.accessdata.fda. gov/scripts/cdrh/cfdocs/cfmaude/search.cfm. 39. Shah JS, Maisel WH: Recalls and safety alerts affecting automated external defibrillators. JAMA 296:655-660, 2006. 40. Hauser RG, Kallinen LM, Almquist AK, et al: Early failure of a small-diameter high-voltage implantable cardioverterdefibrillator lead. Heart Rhythm 4:892-896, 2007. 41. Maisel WH: Implantable cardioverter-defibrillator lead complication: when is an outbreak out-of-bounds? Heart Rhythm 5:1673-1674, 2008. 42. Padeletti L, Pappone C, Curnis A, et al: Product-experience reporting on endocardial defibrillation leads: a 4-year national perspective. Expert Rev Med Devices 6:383-388, 2009. 43. US Food and Drug Administration: MedSun: Medical Product Safety. www.fda.gov/MedicalDevices/Safety/MedSunMedical ProductSafetyNetwork/default.htm. 44. National Cardiovascular Data Registry: ICD Registry. https:// www.ncdr.com/webncdr/ICD/Default_ssl.aspx. 45. Hammill SC, Kremers MS, Kadish AH, et al: Review of the ICD Registry’s third year, expansion to include lead data and pediatric ICD procedures, and role for measuring performance. Heart Rhythm 6:1397-1401, 2009. 46. Duru F, Luechinger R, Scharf C, Brunckhorst C: Automatic impedance monitoring and patient alert feature in implantable cardioverter defibrillators: being alert for the unexpected! J Cardiovasc Electrophysiol 16:444-448, 2005. 47. US Food and Drug Administration: Background and definitions. http://www.fda.gov/Safety/Recalls/ucm165546.htm. 48. Basile EM, Lorell BH: The Food and Drug Administration’s regulation of risk disclosure for implantable cardioverterdefibrillators: has technology outpaced the agency’s regulatory framework? Food Drug Law J 61:251-272, 2006. 49. Tyers GF: FDA recalls: how do pacemaker manufacturers compare? Ann Thorac Surg 48:390-396, 1989. 50. Mahajan T, Dubin AM, Atkins DL, et al: Impact of manufacturer advisories and FDA recalls of implantable cardioverterdefibrillator generators in pediatric and congenital heart disease patients. J Cardiovasc Electrophysiol 19:1270-1274, 2008. 51. Maisel WH, Stevenson WG, Epstein LM: Changing trends in pacemaker and implantable-cardioverter-defibrillator generator advisories. Pacing Clin Electrophysiol 25:1670-1678, 2002. 52. Levine PA, Stanton MS, Sims JJ: High quality performance of pacemakers and implantable defibrillators. Pacing Clin Electrophsyiol 25:1667-1669, 2002. 53. Krahn AD, Simpson CS, Parkash R, et al: Formation of a national network for rapid response to device and lead advisories: the Canadian Heart Rhythm Society Device Advisory Committee. Can J Cardiol 25:403-405, 2009. 54. Stutts LA, Conti JB, Aranda JM, Jr, et al: Patient evaluation of ICD recall communication strategies: a vignette study. Pacing Clin Electrophysiol 30:1105-1111, 2007. 55. Wilkoff BL, Auricchio A, Brugada J, et al: HRS/EHRA Expert Consensus on the monitoring of cardiovascular implantable electronic devices (CIED): description of the techniques, indications, personnel, frequency and ethical considerations. Heart Rhythm 5:907-925, 2008. 56. Maisel WH: Physician management of pacemaker and implantable cardioverter-defibrillator advisories. Pacing Clin Electrophysiol 27:437-442, 2004.

57. Kay GN, Brinker JA, Kawanishi DT, et al: Risks of spontaneous injury and extraction of an active fixation pacemaker lead: report of the Accufix Multicenter Clinical Study and Worldwide Registry. Circulation 100:2344-2352, 1999. 58. Gould PA, Krahn AD: Complications associated with implantable cardioverter-defibrillator replacement in response to device advisories. JAMA 295:1907-1911, 2006. 59. Klug D, Balde M, Pavin D, et al: Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Circulation 116:1349-1355, 2007. 60. Priori SG, Auricchio A, Nisam S, Yong P: To replace or not to replace: a systematic approach to respond to device advisories. J Cardiovasc Electrophysiol 20:164-170, 2009. 61. Amin MS, Ellenbogen KA: Should recent defibrillator and lead advisories affect decisions to refer patients for implantable cardioverter-defibrillator therapy? Curr Opin Cardiol 25:23-28, 2010. 62. Amin MS, Wood MA, Shepard RK, et al: Clinical judgment versus decision analysis for managing device advisories. Pacing Clin Electrophysiol 31:1236-1240, 2008. 63. Al-Khatib SM, Lucas FL, Jollis JG, et al: The relation between patients’ outcomes and the volume of cardioverter-defibrillator implantation procedures performed by physicians treating Medicare beneficiaries. J Am Coll Cardiol 46:1536-1540, 2005. 64. Curtis JP, Luebbert JJ, Wang Y, et al: Association of physician certification and outcomes among patients receiving an implantable cardioverter-defibrillator. JAMA 301:1661-1670, 2009. 65. Amin MS, Matchar DB, Wood MA, Ellenbogen KA: Management of recalled pacemakers and implantable cardioverterdefibrillators: a decision analysis model. JAMA 296:412-420, 2006. 66. Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators: A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 337:1576-1583, 1997. 67. Gold MR, Peters RW, Johnson JW, Shorofsky SR: Complications associated with pectoral cardioverter-defibrillator implantation: comparison of subcutaneous and submuscular approaches. Worldwide Jewel Investigators. J Am Coll Cardiol 28:1278-1282, 1996. 68. Rosenqvist M, Beyer T, Block M, et al: Adverse events with transvenous implantable cardioverter-defibrillators: a prospective multicenter study. European 7219 Jewel ICD Investigators. Circulation 98:663-670, 1998. 69. Kiviniemi MS, Pirnes MA, Eranen HJ, et al: Complications related to permanent pacemaker therapy. Pacing Clin Electrophysiol 22:711-720, 1999. 70. Gould PA, Gula LJ, Champagne J, et al: Outcome of advisory implantable cardioverter-defibrillator replacement: one-year follow-up. Heart Rhythm 5:1675-1681, 2008. 71. Moore JW III, Barrington W, Bazaz R, et al: Complications of replacing implantable devices in response to advisories: a single center experience. Int J Cardiol 134:42-46, 2009. 72. Costea A, Rardon DP, Padanilam BJ, et al: Complications associated with generator replacement in response to device advisories. J Cardiovasc Electrophysiol 19:266-269, 2008. 73. Anderson KP: Estimates of implantable cardioverter-defibrillator complications: caveat emptor. Circulation 119:1069-1071, 2009. 74. Tompkins C, Cheng A, Dalal D, et al: Dual antiplatelet therapy and heparin “bridging” significantly increase the risk of bleeding complications after pacemaker or implantable cardioverterdefibrillator device implantation. J Am Coll Cardiol 55:23762382, 2010. 75. Thal S, Moukabary T, Boyella R, et al: The relationship between warfarin, aspirin, and clopidogrel continuation in the periprocedural period and the incidence of hematoma formation after device implantation. Pacing Clin Electrophysiol 33:385-388, 2010. 76. Jamula E, Douketis JD, Schulman S: Perioperative anticoagulation in patients having implantation of a cardiac pacemaker or defibrillator: a systematic review and practical management guide. J Thromb Haemost 6:1615-1621, 2008. 77. Kaluza GL, Joseph J, Lee JR, et al: Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 35:1288-1294, 2000. 78. Maytin M, Love CJ, Fischer A, et al: Multicenter experience with extraction of the Sprint Fidelis ICD lead. J Am Coll Cardiol 56, 2010. 79. Wilkoff BL, Love CJ, Byrd CL, et al: Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications, and patient management. Heart Rhythm 6:10851104, 2009.

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80. Byrd CL, Wilkoff BL, Love CJ, et al: Clinical study of the laser sheath for lead extraction: the total experience in the United States. Pacing Clin Electrophysiol 25:804-808, 2002. 81. Wazni O, Epstein LM, Carrillo RG, et al: Lead extraction in the contemporary setting: the LExICon study: an observational retrospective study of consecutive laser lead extractions. J Am Coll Cardiol 55:579-586, 2010. 82. Jones SO, IV, Eckart RE, Albert CM, Epstein LM: Large, singlecenter, single-operator experience with transvenous lead extraction: outcomes and changing indications. Heart Rhythm 5:520-525, 2008. 83. Kennergren C, Bjurman C, Wiklund R, Gabel J: A single-centre experience of over one thousand lead extractions. Europace 11:612-617, 2009. 84. Wilkoff BL, Byrd CL, Love CJ, et al: Trends in intravascular lead extraction: analysis of data from 5339 procedures in 10 years. XIth World Symposium on Cardiac Pacing and Electrophysiology, Berlin. Pacing Clin Electrophysiol 22(6 pt II):A207, 1999. 85. Bracke FA, Meijer A, Van Gelder B: Learning curve characteristics of pacing lead extraction with a laser sheath. Pacing Clin Electrophysiol 21:2309-2313, 1998. 86. Smith HJ, Fearnot NE, Byrd CL, et al: Five-years experience with intravascular lead extraction. U.S. Lead Extraction Database. Pacing Clin Electrophysiol 17:2016-2020, 1994. 87. Ghosh N, Yee R, Klein GJ, et al: Laser lead extraction: is there a learning curve? Pacing Clin Electrophysiol 28:180-184, 2005. 88. Hauser RG, Katsiyiannis WT, Gornick CC, et al: Deaths and cardiovascular injuries due to device-assisted implantable cardioverter-defibrillator and pacemaker lead extraction. Europace 12:395-401, 2010. 89. Glikson M, Suleiman M, Luria DM, et al: Do abandoned leads pose risk to implantable cardioverter-defibrillator patients? Heart Rhythm 6:65-68, 2009. 90. Silvetti MS, Drago F: Outcome of young patients with abandoned, nonfunctional endocardial leads. Pacing Clin Electrophysiol 31:473-479, 2008. 91. Kallinen LM, Hauser RG, Lee KW, et al: Failure of impedance monitoring to prevent adverse clinical events caused by fracture of a recalled high-voltage implantable cardioverter-defibrillator lead. Heart Rhythm 5:775-779, 2008. 92. Simons EC, Feigenblum DY, Nemirovsky D, Simons GR: Alert tones are frequently inaudible among patients with implantable cardioverter-defibrillators. Pacing Clin Electrophysiol 32:12721275, 2009. 93. Kallinen LM, Hauser RG, Tang C, et al: Lead integrity alert algorithm decreases inappropriate shocks in patients who have Sprint Fidelis pace-sense conductor fractures. Heart Rhythm 7:1048-1055,2010. 94. Swerdlow CD, Gunderson BD, Ousdigian KT, et al: Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads. Circulation 118:2122-2129, 2008. 95. Sears SF, Todaro JF, Lewis TS, et al: Examining the psychosocial impact of implantable cardioverter-defibrillators: a literature review. Clin Cardiol 22:481-489, 1999. 96. Sears SF, Matchett M, Conti JB: Effective management of ICD patient psychosocial issues and patient critical events: clinical reviews. J Cardiovasc Electrophysiol 20:1297-1304, 2009. 97. Undavia M, Goldstein NE, Cohen P, et al: Impact of implantable cardioverter-defibrillator recalls on patients’ anxiety, depression, and quality of life. Pacing Clin Electrophysiol 31:1411-1418, 2008. 98. Birnie DH, Sears SF, Green MS, et al: No long-term psychological morbidity living with an implantable cardioverter-defibrillator under advisory: the Medtronic Marquis experience. Europace 11:26-30, 2009. 99. Gibson DP, Kuntz KK, Levenson JL, Ellenbogen KA: Decisionmaking, emotional distress, and quality of life in patients affected by the recall of their implantable cardioverterdefibrillator. Europace 10:540-544, 2008. 100. Cuculi F, Herzig W, Kobza R, Erne P: Psychological distress in patients with ICD recall. Pacing Clin Electrophysiol 29:12611265, 2006. 101. Sears SF, Jr, Conti JB: Psychological aspects of cardiac devices and recalls in patients with implantable cardioverter defibrillators. Am J Cardiol 98:565-567, 2006. 102. Fisher JD, Koulogiannis KP, Lewallen L, et al: The psychological impact of implantable cardioverter-defibrillator recalls and the durable positive effects of counseling. Pacing Clin Electrophysiol 32(8):1012-1016, 2009.

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35  35

Ethical Issues RACHEL LAMPERT  |  DAVID HAYES

CASE 1 The family member of a recently deceased ICD patient recounted the following in an interview1: “His defibrillator kept going off. … It went off 12 times in one night. … He went in, and they looked at it; they said they adjusted it, and they sent him back home. The next day we had to take him back because it was happening again. It kept going off and going off, and it wouldn’t stop going off.” CASE 2 A 65-year-old man (FG) received an ICD 10 years ago after a cardiac arrest (ejection fraction, 30%). He had shock-treated ventricular tachycardia at 250 bpm four times in the last 10 years. He was last seen in person 8 months ago while being followed transtelephonically. In the meantime, his wife called his electrophysiologist and said FG was currently on the oncology floor, having been diagnosed 4 months ago with metastatic cancer. Despite multiple rounds of chemotherapy, FG still had lesions in his brain and bone. He was to be discharged to hospice the following day on a morphine drip. The patient and family requested that ICD therapies be turned off. The EP team deactivated therapies, and FG died in hospice 2 days later, “peacefully,” according to his wife.

The most common ethical issue facing physicians and other health care providers who care for patients with cardiac implantable electronic devices (CIEDs) is that of device deactivation in patients nearing the end of their life or who otherwise request that device therapies be deactivated. Most clinicians (physicians, nurses, and other health care providers) who care for patients with CIEDs have participated in device deactivations.2 However, their understanding of the legal and ethical issues surrounding device deactivation varies, as do clinicians’ attitudes toward deactivation.2,3 Further, as one study reported, 20% of implantable cardioverter-defibrillator (ICD) patients receive shocks in the last weeks of their lives, as illustrated by Case 1. Few patients or families discuss the option with device deactivation with their physicians before the days preceding death, even patients with “do not resuscitate” orders.1 Likewise, few clinicians initiate discussions with patients or family members regarding device deactivations, even when the patient’s situation is terminal. As the population of patients benefiting from and receiving CIEDs continues to grow, clinicians will increasingly care for CIED patients dying of nonarrhythmic, often slow processes, such as cancer and heart failure. Situations such as described in Case 1, in which CIEDs cause pain and reduce quality of life in patients at the end of their life, may likely become more common. Case 2 illustrates how management of CIED therapies in dying patients can be addressed in ways more beneficial to patients and families. To address the uncertainties surrounding CIED deactivation and provide direction for clinicians in these difficult circumstances, the Heart Rhythm Society (HRS) published recommendations regarding deactivation, with input from electrophysiologists, patients, and representatives from the fields of geriatrics, palliative care, psychiatry, nursing, law, ethics, and divinity, as well as industry and patient groups.4

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Ethical and Legal Principles Underlying CIED Deactivation Basic ethical principles applicable to patient care include respect for patient autonomy (the duty to respect patients and their rights of selfdetermination), beneficence (the duty to promote patient interests), nonmaleficence (the duty to prevent or not harm patients), and justice, referring in part to the duty to treat patients and distribute health care resources fairly.5 Informed consent, the most important legal doctrine in the clinician-patient relationship, derives from the ethical principle of respect for persons; autonomy is maximized when patients understand the nature of their diagnoses and treatment options and participate in decisions about their care. The rationale for informed consent is simple: it is the patient’s body and life—the patient must live with the consequences of the treatment—and thus the patient has the most at stake in the decision.6 Clinicians are ethically and legally obligated to ensure that patients are informed about their diagnoses and treatment options.7,8 The U.S. courts have ruled that the right to make decisions about medical treatments is both a common law (derived from court decisions) right based on bodily integrity and self-determination and a constitutional right based on privacy and liberty.6 A corollary to informed consent is informed refusal. A patient has the right to refuse any treatment, even if the treatment prolongs life, or death would follow a decision not to use it. A patient also has the right to refuse a previously consented treatment if the treatment no longer meets the patient’s health care goals, if those goals have changed (e.g., from prolonging life to minimizing discomforts), or if the perceived burdens of the patient’s illness (e.g., quality of life) and ongoing treatment outweigh the perceived benefits of ongoing treatment.6,9-11 Honoring these decisions is an integral part of patient-centered care. If a clinician initiates or continues a treatment that a patient has refused, then ethically and legally the clinician is committing “battery,” regardless of the clinician’s intent.7 Finally, granting requests to withdraw life-sustaining treatments from patients who do not want them, is respecting a right to be left alone and to die naturally of the underlying disease, a legally protected right based on the right to privacy. This has been phrased as “a right to decide how to live the rest of one’s life.” A patient’s right to withdraw unwanted treatment has been consistently upheld by U.S. courts (Table 35-1). In the In re Quinlan case, the New Jersey Supreme Court ruled that the patient had both common law and constitutional rights to refuse continued ventilator support, even though her clinicians believed she would die without it.12 In the Cruzan v. Director, Missouri Department of Health case, which involved a feeding tube, the U.S. Supreme Court ruled the same way; that is, patients have the right to refuse life-sustaining treatments. The Court also ruled that a feeding tube was a medical treatment and that it did not have unique status.13 Whether a feeding tube had unique status was raised again during the Terri Schiavo case. The courts again ruled adult patients have a constitutional right to refuse any treatment, including life-sustaining treatments, and that there is no legal difference between withdrawing an ongoing treatment and not starting it in the first place.14



35  Ethical Issues

TABLE

35-1 

1041

Landmark Legal Cases Confirming the Right to Withhold or Withdraw Life-Sustaining Therapies

Case In re Quinlan Saikewicz In the matter of Shirley Dinnerstein Spring Barber Bouvia Cruzan v. Director, Missouri Department of Health Schiavo*

Year 1976 1977 1978 1980 1983 1985 1990

Court Supreme Court of New Jersey Massachusetts Superior Judicial Court Massachusetts Court of Appeals Massachusetts Superior Judicial Court California Court of Appeals California Court of Appeals U.S. Supreme Court

Withhold/Withdraw Withdrawal Withholding Withholding Withdrawal Withdrawal Both Withdrawal

Therapy Ventilator Chemotherapy Cardiopulmonary Resuscitation Hemodialysis Intravenous fluids Feeding tube Feeding tube

2005

Florida Court of Appeals*

Withdrawal

Feeding tube

*The Florida Supreme Court declined to consider case, the U.S. Supreme Court declined to hear related case.

In none of these cases did the courts distinguish between types of life-sustaining treatments. The law applies to the person, and informed consent is a right of the patient—it is not specific to any one medical intervention.6,14-16 Thus, even though the Supreme Court has not specifically commented on the question of pacemaker or ICD deactivation, because CIEDs deliver life-sustaining therapies, discontinuation of these therapies is clearly addressed by the previous Supreme Court precedents upholding the right to discontinue life-sustaining treatment. In addition, these rights extend to patients who lack decisionmaking capacity, through previously expressed statements (e.g., advance directive) and surrogate decision makers.11,14,17 When patients lack decision-making capacity because of medical illness (e.g., dementia), clinicians must rely on surrogates to make decisions. If the patient has an advance directive (AD) that identifies a surrogate, the patient’s choice of surrogate should be respected7 (see later). In the absence of an AD, clinicians must identify the legally recognized appropriate surrogate. The ideal surrogate is one who best understands the patient’s health care–related goals and preferences. Many U.S. states, however, specify by law a hierarchy of surrogate decision makers (e.g., spouse, followed by adult child, and so on). When making decisions, a surrogate should adhere with the instructions in the patient’s AD (if one exists) and base decisions on the patient’s—not the surrogate’s— values and preferences if known (i.e., the “substituted judgment” standard).18 Although both the law and ethics are clear—a patient has the right to refuse and request the withdrawal of CIED therapies regardless of whether he or she is terminally or irreversibly ill, and regardless of whether the therapies prolong life and death would follow a decision not to use them7—some clinicians who care for patients with CIEDs see a moral distinction between deactivating an ICD and deactivating a pacemaker, particularly in a dependent patient.2 However, while some have questioned whether pacemaker deactivation is similar to assisted suicide or euthanasia,2 there are several key differences between withdrawal of CIED therapies and assisted suicide. First is the issue of clinician intent. When a physician complies with a patient’s request to deactivate a device, the physician’s intent is to remove a treatment that is perceived by the patient as burdensome or is simply unwanted. Although this may have the effect of allowing the patient to die of an underlying disease,12,16,19 hastening death should not be the clinician’s primary intent.7,10,20 In contrast, in assisted suicide, the patient intentionally terminates his own life using a lethal method provided or prescribed by a clinician. In euthanasia, the physician directly and intentionally terminates the patient’s life (e.g., lethal injection). The second point differentiating withdrawal of an unwanted therapy from assisted suicide and euthanasia lies in the cause of death. In assisted suicide or euthanasia, death is caused by the intervention provided, prescribed, or administered by the clinician. In contrast, when a patient dies after a treatment is refused or withdrawn, the cause of death is the underlying disease. There are clearly nuances to this issue. For example, a pacemaker-dependent patient with depression

may request deactivation of the pacemaker because life itself is burdensome. In such situations it is important to determine the decisionmaking capacity of the patient. The U.S. Supreme Court decisions have made a clear distinction between withdrawing life-sustaining treatments and assisted suicide and euthanasia. In the case of Vacco v. Quill,21 Chief Justice Rehnquist wrote: The distinction comports with fundamental legal principles of causation and intent. First, when a patient refuses life-sustaining medical treatment, he dies from an underlying fatal disease or pathology; but if a patient ingests lethal medication prescribed by a physician, he is killed by that medication. … [In Cruzan] our assumption of a right to refuse treatment was grounded not. … on the proposition that patients have a … right to hasten death, but on well established, traditional rights to bodily integrity and freedom from unwanted touching. The Court ruled that all patients have a constitutional right to refuse treatment, but no one has a constitutional right to assisted suicide or euthanasia. In another case,22 the Court ruled that clinicians can legally (and should, from an ethical perspective) provide patients with whatever treatments needed to alleviate suffering, such as morphine, even if the treatments might hasten death. Criminality is determined by the clinician’s intent. Legal precedent does not distinguish between types of unwanted therapies, but there are aspects of pacing therapies in a dependent patient that some clinicians have found problematic. For example, ICD therapies are intermittent whereas pacemaker therapy in a pacemakerdependent patient is continuous; death might not occur immediately after ICD deactivation, whereas death might occur quickly after pacemaker deactivation. However, widespread agreement exists that withdrawing other continuous life-sustaining treatments, such as mechanical ventilation, is ethically and legally permissible. Similarly, clinicians may consider duration of therapy as morally important when considering requests to withdraw life-sustaining treatments. However, withdrawal of other long-term life-sustaining treatments, such as hemodialysis and artificial hydration and nutrition, is well accepted.23 Another concern expressed about withdrawing CIED therapies is that the devices, unlike other life-sustaining treatment, are completely internal. However, the ethical and legal principles involved in the right to refuse treatment are not based on the location of the therapy. Thus, the fact that pacemakers provide therapy that is continuous, internal, and of long duration does not detract from the permissibility of carrying out requests to withdraw this therapy from patients who no longer want it. Some disagreement exists regarding whether a pacemaker is a substitutive therapy, one that substitutes for a pathologically lost function, or a replacement therapy, one that replaces a pathologically lost function. There is agreement that substitutive life-sustaining treatments, such as hemodialysis for kidney failure or a ventilator for respiratory failure, can be withdrawn. A replacement therapy, such as kidney

1042

SECTION 4  Follow-up and Programming

transplantation for kidney failure, literally becomes “part of the patient” and provides the lost function in the same fashion as did the patient’s own body. Replacement therapies also respond to physiologic changes in the host and are independent of external energy sources and control of an expert. Removing or withdrawing a replacement life-sustaining treatment has been characterized as “euthanasia.”23 CIED therapies, including pacemaker support in a pacemakerdependent patient, lack the features of replacement therapies and therefore are most often characterized as “substitutive,”24 although this distinction has been questioned.19 A transplanted kidney, however, has all the features of a replacement therapy. Most would regard carrying out a request to deactivate a pacemaker in a terminally-ill patient as far less morally problematic than carrying out a request to remove a transplanted kidney in the same patient. Deactivating a pacemaker is noninvasive and does not introduce a new pathology (although it may precipitate heart failure symptoms). Removing a kidney, however, is invasive and introduces a new pathology (i.e., a wound). ETHICAL PRINCIPLES UNDERLYING, THE DECISION-MAKING PROCESS Who decides about device deactivation? Ethically and legally, competent patients (or their surrogates) have authority to make decisions. Patients’ decisions have priority over clinicians’ decisions. Because a clinician regards a patient’s decision as “wrong” does not mean the decision is irrational. What criteria should go into making the decision? The patient and physician together must determine a treatment’s effectiveness and the benefits and burdens in the context of the patient’s illness and quality of life. A treatment’s effectiveness is its ability to alter the natural history of a disease. CIEDs are effective, for example, in bypassing life-threatening cardiac conduction abnormalities or treating fatal arrhythmias. However, treatment effectiveness is not the same as treatment benefits and burdens. Benefit is determined by the patient: the patient’s assessment of the treatment’s value. Burden is also determined by the patient: the patient’s assessment of the existing and potential discomforts, costs, and inconveniences associated with the illness and its treatment as the patient perceives it.9 Each patient is unique and weighs such benefits and burdens in relation to their own values, preferences, and health care–related goals. What one patient perceives as beneficial and nonburdensome may be viewed by another patient as nonbeneficial and burdensome. Because benefit and burden are determined by the patient, a patient may decide the burden of CIED therapy outweighs the benefit even if he is not terminally ill. Although patients are the ultimate decision makers, conflicts between caregivers and patients can arise, often when there is misunderstanding among patients and clinicians on goals of care. For example, a clinician may view ongoing CIED therapy in a terminally ill patient as effective, beneficial, and nonburdensome. The patient (or surrogate), however, may strongly disagree. Multidisciplinary care conferences, ethics consultation, and palliative care consultation can be very helpful in resolving these conflicts, especially in clarifying goals of care, establishing the permissibility of withdrawing CIED therapies (and contingency plans if a decision is made not to withdraw CIED therapies), and formulating care plans. Ethics consultation is not required before device deactivation. However, this may be helpful in ambiguous situations such as conflict between members of a family or disagreement between members of the health care team caring for a patient, or caregivers may find that additional support is needed when pursuing a particular treatment course.25 If the decision-making capacity of the patient is in question, or if there are suspicions of coercion, ethics consultation can also be helpful. The Joint Commission requires that health care institutions have processes for addressing ethical concerns that arise in the care of patients.26 Case 3, describing disagreement among both family and caregivers, and case 4, an ambiguous case illustrating possible coercion, illustrate examples in which ethics consultation may be helpful:

CASE 3 An 81-year-old woman with complete atrioventricular (AV) block and no structural heart disease received a permanent DDD pacemaker 18 years ago; the generator was replaced 8 years ago. She is now in a nursing home with progressive dementia. Her son calls and asks if her cardiologist can come and turn off her pacemaker. The cardiologist feels uncomfortable honoring this wish, although the pacemaker nurse who would actually perform the deactivation does not. Before any decisions are made, a daughter calls saying her mother would never want her pacemaker deactivated. CASE 4 An 85-year-old woman had received a pacemaker for congestive heart block 2 years ago. Although her religious group does not believe in implanted devices, she agreed to the device in the hospital. Now, however, she wants to enter an assisted-living/ nursing facility run by her group, but they will not accept her with an active pacemaker. She requests deactivation.

Advance care planning can often prevent ethical dilemmas at the end of life. In this process, which promotes patient autonomy, a patient identifies his or her values, preferences, and goals regarding future health care (e.g., at the end of life) and a surrogate decision maker in the event the patient loses decision-making capacity.7 Ideally, the patient should discuss values and preferences with care providers and potential surrogate decision makers, who should document them in the patient’s medical record, and the patient should complete an advance directive. There are two forms of ADs: the durable power of attorney for health care and the living will. The durable power of attorney for health care allows the patient to specify a surrogate in the event the patient loses decision-making capacity. The living will allows the patient to list specific health care–related values, goals, and preferences. From an ethics standpoint, clinicians should view the AD as an extension of the autonomous person and therefore should respect the values, goals, and preferences listed in the AD. From a legal standpoint, all 50 U.S. states recognize ADs as an extension of the autonomous person. In fact, the Patient Self-Determination Act, passed by Congress in 1990 in response to the Cruzan decision, requires that health care institutions that participate in Medicare and Medicaid programs ask patients whether they have an AD, inform patients of their rights to accept or refuse medical treatments and to create and execute an AD, and to incorporate ADs into patients’ medical records.27 Rights and Responsibilities of Clinicians for Whom Deactivation Is Counter to Their Personal Beliefs Regardless of the ethical and legal permissibility of carrying out requests to withdraw CIED therapies from patients who have (or their surrogate has) made this decision, clinicians—like patients—are moral agents whose personal values and beliefs may lead them to prefer not to participate in device deactivation. A recent survey found that about 10% of clinicians who care for patients with CIEDs view pacemaker deactivation in a pacemaker-dependent patient as a form of assisted suicide or euthanasia.2 Others object to pacemaker deactivation because they believe pacemaker therapy does not prolong the dying process or cause physical discomfort (unlike ICD shocks) and that pacemaker deactivation may cause discomfort (e.g., worsened heart failure symptoms).28 These burdens are ultimately determined by the patient, but clinicians and others, including industry employed allied professionals, should not be compelled to carry out device deactivations if they view the procedure as inconsistent with their personal values.8,28 Under these circumstances, the clinician should inform the patient of the clinician’s preference not to perform CIED deactivation. However, as described in the American Medical Association (AMA) Code of Medical Ethics,29 the clinician should not impose his or her values on or abandon the patient and should ensure that they do not cause the patient emotional distress.30 Instead, the clinician and patient should work to achieve a mutually agreed-upon care plan. If such a



35  Ethical Issues

TABLE

35-2 

1043

Physician-Initiated Discussions with Implant Patients

Timing of Conversation Before implantation

After an episode of increased or repeated firings from an ICD Progression of cardiac disease, including repeated hospitalizations for heart failure and/or arrhythmias When patient/surrogate chooses a “do not resuscitate” (DNR) order* Patients at end of life

Points to Discuss Clear discussion of benefits and burdens of device. Brief discussion of potential future limitations or burdensome aspects of device therapy. Encourage patients to have some form of advance directive. Inform of option to deactivate device in the future. Discussion of possible alternatives, including adjusting medications, adjusting device settings, and cardiac procedures to reduce future shocks. Reevaluation of benefits and burdens of device. Assessment of functional status, quality of life, and symptoms. Referral to palliative and supportive care services. Reevaluation of benefits and burdens of device. Exploration of patient’s understanding of device and how patient conceptualizes it with regard to external defibrillation. Referral to palliative care or supportive services. Reevaluation of benefits and burdens of device. Discussion of option of deactivation addressed with all patients, although deactivation not required.

Helpful Phrases to Consider “It seems clear at this point that this device is in your best interest, but you should know at some point if you become very ill from your heart disease or another process you develop in the future, the burden of this device may outweigh its benefit. While that point is hopefully a long way off, you should know that turning off your defibrillator is an option. ” “I know that your device caused you some recent discomfort and that you were quite distressed. I want to work with you to see if we can adjust the settings to assure that the device continues to work in the appropriate manner. If we can’t get you to that point, then we may want to consider turning it off altogether, but let’s try some adjustments first.” “It appears as though your heart disease is worsening. We should really talk about your thoughts and questions about your illness at this point and see if your goals have changed at all.” “Now that we’ve established that you would not want resuscitation in the event your heart were to go into an abnormal pattern of beating, we should reconsider the role of your device. In many ways it is also a form of resuscitation. Tell me your understanding of the device, and let’s talk about how it fits into the larger goals for your medical care at this point.” “I think at this point we need to reconsider your [device]. Given how advanced your disease is, we need to discuss whether it makes sense to keep it active. I know this may be upsetting to talk about, but can you tell me your thoughts at this point?”

Modified from Lampert R, Hayes DL, Annas GJ, et al: Heart Rhythm Society Expert Consensus Statement on the management of cardiovascular implantable electronic devices (CIEDs) in patients nearing end of life or requesting withdrawal of therapy. Heart Rhythm 7:1008-1026, 2010. *Patients may choose to forego intubation, CPR, and external defibrillation while at the same time deciding to keep the defibrillation function of their ICD active. A patient’s choice to be “DNR” may or may not be concomitant with a decision to withdraw CIED therapy, as resuscitation interventions and the ICD each carries its own benefits and burdens.

plan cannot be achieved, the primary clinician should involve a second clinician who is willing to comanage the patient and provide legally permissible care and procedures, including CIED deactivation.28,29 It is important for the health care team to recognize and address any conflicts within the team. It is also the responsibility of the institution to ensure that services that are legal and that may be requested by the patient are available. Preventing Both Ethical Dilemmas and Painful Shocks at End of Life: Importance of Early, Proactive Communication “It hadn’t occurred to me to turn it off until [the cardiology fellow said] you could turn these things off and I’m like, ‘oh, okay.’ I mean it wasn’t something that I had ever encountered, and it crossed my mind on a technical level, but not really, ‘Oh, I should have this conversation.’ ” ICD patient31 CASE 5 A 74-year-old woman had an ICD inserted 5 years ago after her first episode of ventricular tachycardia. As her heart disease progressed, the episodes of ventricular tachycardia increased. While at home one afternoon, her defibrillator shocked her several times, and she was admitted to the hospital. She went in and out of consciousness and was hemodynamically unstable for the next 72 hours. After a long family meeting, her family and cardiologist decided that no further aggressive treatments would be continued and that her care would focus on comfort. During the night, her ICD shocked her 10 times, while her nurse tried desperately to contact someone to turn off her ICD. Finally, at 3 am, the cardiologist came in and deactivated the ICD. She died 2 hours later.17

Timely and effective communication among patients, families, and health care providers is essential to informed consent and to prevent situations such as described in Case 5. Effective communication includes determining the patient’s goals of care, helping the patients weigh the benefits and burdens of device therapy as his clinical situation changes, clarifying the consequences of deactivation, and

discussing potential alternative treatments, as well as encouraging the patient to complete an AD. Clinicians must take a proactive role in discussions about the option of deactivation in the context of the patient’s goals for care. These conversations should continue over the course of the patient’s illness. As illness progresses, patient preferences for outcomes and the level of burden acceptable to a patient may change.32,33 Advanced care planning conversations improve outcomes for both patients and their families,34 as patients with ICDs who engage in advance care planning are less likely to experience shocks while dying because ICD deactivation has occurred.35 Studies show that patients and families desire conversations about end-of-life care.36-38 Few patients with CIEDs discuss device deactivation with their clinicians or know that device deactivation is an available option.1,3,31 Even though many patients with CIEDs have ADs, very few of them mention the device specifically in their ADs.39 Clinicians must take a proactive role in initiating discussions about the option of deactivation, from the time of implantation throughout a patient’s life as the clinical situation changes (Table 35-2). The complexity of these conversations, however, is evident in data from physicians demonstrating that although they believe they should engage in these types of conversations with patients, they rarely do.1,3,31 DISCUSSION OF DEVICE DEACTIVATION WITH OVERALL GOALS OF CARE Communication techniques used to discuss the role of the device need to move from treatment-directed conversations to goal-directed conversations. In other words, asking patients and their families, “Do you want the device to remain on?” is often as misleading and misunderstood by them as the question, “Do you want everything done?” Without a better understanding of their current state of health and the role of the cardiac device, patients cannot make fully informed decisions. Table 35-3 outlines the steps needed for goal-directed communication and some useful phrases to begin conversations at each point. These conversations should include a discussion of quality of life, functional status, perceptions of dignity, and both current and potential future symptoms, because each of these elements can influence

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TABLE

35-3 

SECTION 4  Follow-up and Programming

Steps for Communicating with Patients and Families about Goals of Care with CIEDs

Step 1.  Determine what patients/families know about their illness. 2.  Determine what the patient and family know about the role that the device plays in their health both now and in the future. 3.  Determine what additional information the patient and family want to know about the patient’s illness. 4.  Correct or clarify any misunderstandings about the current illness and possible outcomes, including the role of the device. 5.  Determine the patient and family’s overall goals of care and desired outcomes.

6.  Using the stated goals as a guide, work to tailor treatments, and in this case the management of the cardiac device, to those goals.

Sample Phrase to Begin Conversation “What do you understand about your health and what is occurring in terms of your illness?” “What do you understand the role of the [CIED] to be in your health now?

“What else would be helpful for you to know about your illness or the role the [CIED] plays within it?

“I think you have a pretty good understanding of what is happening in terms of your health, but there are a few things I would like to clarify with you.” “Given what we’ve discussed about your health and the potential likely outcomes of your illness, tell me what you want from your health care at this point.” Note: Sometimes patients and families may need more guidance at this point, so some potential guiding language might be: “At this point some patients tell me they want to live as long as possible, regardless of the outcome, whereas other patients tell me that the goal is to be as comfortable as long as possible while also being able to interact with their family. Do you have a sense of what you want at this point?” Phrases to be used here depend on the goals as set by the patient and family. For a patient who states that her desired goal is to live as comfortably as possible for whatever remaining time she has left: “Given what you’ve said about assuring that you are as comfortable as possible it might make sense to deactivate the shocking function of your ICD. What do you think about that?” or For a patient who states he wants all life-sustaining treatments to be continued, an appropriate response might be, “In that case, perhaps leaving the antiarrhythmia function of the device active would best be in line with your goals. However, you should understand that this may cause you and your family discomfort at the end of life. We can make a decision at a future point in time about turning the device off. Tell me your thoughts about this.”

Table adapted from references 1, 35, 38, 48, and 49. CIEDs, Cardiac implantable electronic devices.

how patients set goals for their health care. Step 2 is particularly important, because data shows that some patients with ICDs do not understand the role the device plays in their health, particularly in terms of care at the end of life.40 The goal is not to overburden patients with decisions, but to determine an overall set of guiding principles by which clinicians can help patients make decisions. These conversations should follow the model of “shared decision making” in which clinicians work together with patients and families to ensure that patients understand, in the context of their illness, the benefits and burdens of a particular treatment and the potential outcomes that may result from its continued use or discontinuation.41 Clinicians must also recognize that while the ultimate power for decision making rests with patients, they may be influenced by factors such as family, culture, or religion. Likewise, although cost should not play a role in the ways that clinicians counsel patients and families, cost does influence the way that some patients make decisions. Studies of patients with serious illness note that many families often lose their savings as well as a major source of income from either the illness itself or from other family members having to care for the patient.41,42 In addition, many of these factors may influence a patient to cede the power of decision making to other individuals. Benefits/Burdens of Ongoing Device Therapy; Consequences/Uncertainties of Deactivation An important role for the clinician is to provide factual information concerning the beneficial and negative effects of continuing device therapy. The patient can then assess how the benefits and burdens of continued therapy fit with ongoing health care goals. It is also vital for both the health care provider and the patient to have an accurate understanding of the expected consequences of device deactivation. Although in some cases (e.g., patients who are 100% pacemaker dependent) this may be relatively straightforward, in many situations it will be difficult to predict a patient’s clinical course after deactivation. The timing and lethality of tachyarrhythmias are unpredictable, and bradyarrhythmias may variously manifest with syncope, heart failure, angina, fatigue, or sudden death. Consultation with a clinical electrophysiologist may help clarify the clinical picture, although significant

uncertainty will remain in many cases. Case 6 illustrates the importance of communication with the family regarding the unpredictability of consequences of deactivation of ICD therapies: CASE 6 An 80-year-old man with dilated cardiomyopathy in rural Florida received a biventricular ICD for left bundle branch block (LBBB) and congestive heart failure (CHF). He later developed progressive CHF and became bedbound and hypotensive. He had no history of ventricular arrhythmias treated with shocks or antitachycardia pacing (ATP). His daughter asks if the ICD can be turned off immediately. An industry-employed allied professional (IEAP) went to the home and deactivated ATP therapies. The daughter then became angry toward both the IEAP and electrophysiology (EP) team when her father did not die immediately, stating she had a plane to catch to return home.

Once a patient’s goals of care are determined, knowledge about a specific device, whether pacemaker, ICD, or cardiac resynchronization therapy (CRT) device, is essential to determining how to change its settings consistent with the patients’ goals regarding survival and quality of life. Pacemaker and CRT therapy are indicated for the amelioration of symptoms caused by bradycardia and heart failure, respectively.43 For patients who have no underlying intrinsic rhythm (“pacemaker dependent”), pacing also provides life-sustaining therapy. Pacemaker dependence, however, can vary over time.44 In a pacemakerdependent patient, death may follow immediately after cessation of pacing therapy. If the patient is not pacemaker dependent, the dying process is unpredictable, and patients need to be assessed closely for symptoms of distress. Deactivation of pacing therapy may result in symptoms that worsen the quality of life (QOL) of a patient who is not pacemaker dependent, but appropriate symptom control in this group can be used effectively to ensure comfort.44 If CRT improves heart failure or reduces arrhythmia burden, discontinuation may impact survival as well as symptoms and QOL. However, ICDs do not improve symptoms, and shocks from an ICD have added to patient and family suffering when the device has fired at the end of life.1,17,28



35  Ethical Issues

Deactivation of ICD shock therapy may thus improve QOL in such patients by eliminating the pain and emotional distress associated with the delivery of noxious ICD discharges. Elimination of defibrillation therapy is less likely to result in immediate death unless the patient is experiencing incessant or increasingly frequent ventricular arrhythmias. In addition to deactivation, other options for treatment withdrawal are available. Patients and their surrogates may choose not to replace devices as their generators become depleted.45,46 Further, partial or selective deactivation of therapies is an option. Patients or surrogates can determine whether they wish to terminate the ATP or CRT components, or only the shocking function. The complex interaction between determining a patient’s goals of care and the options for CIED management shows that there is no “one size fits all” approach to decision making in patients with advanced illness. Instead, only by clearly examining a patient’s understanding and desired (and undesirable) outcomes can clinicians work with patients and families to ensure appropriate device management at the end of a patient’s life to enhance quality of care while maintaining function and reducing symptom burden. Discussion of Potential Alternative Treatments CASE 7 A 21-year-old man presented with recurrent syncope caused by polymorphic ventricular tachycardia and received a defibrillator as therapy. Multiple shocks caused by recurrent episodes of torsades de pointes (electrical storm) resulted in his request to have the defibrillator removed. Prolongation of the number of intervals to detect, as well as eventual success of empirical antiarrhythmic therapy, resulted in resolution of the episodes of torsades de pointes and resultant shocks. The patient withdrew his request for defibrillator removal.

As part of the decision-making process for deactivation of some or all CIED therapies in a particular patient, the physician should consider and advise the patient of alternative therapies that might impact the decision. For example, patients with recurrent ventricular arrhythmias resulting in painful ICD shocks may be candidates for reprogramming of ATP therapies, catheter ablation, or pharmacologic treatments and may benefit from referral to a center with expertise in these techniques. Patients with worsening congestive heart failure may be candidates for advanced therapies such as left ventricular assist devices (LVADs) or cardiac transplantation. SUPPORTING PARTICIPANTS IN THE DECISIONMAKING PROCESS The Family Although the ultimate decision regarding treatments rests with the patient (or legal surrogate), conversations about device deactivation optimally occur with the support of the family. Although the primary individuals providing a patient support are generally the partner or blood relative,47 it is important for the health care team to understand the patient’s extended support network, both to help maintain the patient’s overall health and for guidance when the patient can no longer make decisions. In addition to the formal written AD, conversations among members of the health care team, patient, and family in early phases of the patient’s course of disease will help put the entire family “on the same page” in terms of the goals of medical care.48 Health care providers play an important role in supporting the patient’s surrogate and facilitating communication and support of additional family members. Health Care Providers Key members of the patient’s health care team should be included in deactivation discussions. The patient’s electrophysiologist and cardiologist should be included in deactivation conversations whenever possible, both because they are a member of the care team for these patients, and also to assure that all therapeutic options available to

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meet the patient’s goals can be evaluated. An interdisciplinary approach is essential to support the patient and family. Nurses, social workers, and clergy often play a key role in helping patients understand the device in terms of the overall context of their health and help them better comprehend aspects of their care related to device management. Psychiatric Consultation CASE 8 A 69-year-old man with coronary artery disease (CAD), left ventricular ejection fraction (LVEF) of 30%, and New York Heart Association (NYHA) Class I received a prophylactic ICD 2 years earlier. He has never used the ICD. After his wife dies, he comes to clinic and asks that his ICD be turned off. CASE 9 A 20-year-old woman with tetralogy of Fallot underwent surgical repair at age 6 complicated by congestive heart block requiring a permanent pacemaker (PPM). She was married at age 19, but less than 1 year later divorced and returned to live with her mother. She comes to clinic and asks that the pacemaker be turned off.

Routine psychiatric consultation is not needed for patients who are considering device deactivation. It should be reserved for cases where health care providers or families have concerns that a particular psychiatric disorder may be interfering with the patient’s ability to make informed decisions. Examples include major depression, where a “death wish” exists in the patient with untreated depression or thought disorders (e.g., paranoid delusions). For example, in cases 8 and 9, the potential for depression should be evaluated by a psychiatrist. Neuropsychiatric disorders, including delirium and dementia, can also impact decision-making ability. When in doubt, a psychiatric consultation can help the team assess for adequate decision-making ability at a specific point of time. Palliative Care Specialists CASE 10 A 74-year-old man (JE) was admitted to the cardiac care unit in cardiogenic shock. He was intubated, an intra-aortic balloon pump was emergently inserted, and multiple vasoactive agents were started. JE was weaned from the intra-aortic balloon pump 3 days later and extubated 1 week later. However, JE’s condition progressively worsened, with the onset of sepsis and early signs of renal and liver failure. His level of consciousness vacillated between periods of confusion and periods of lucidity. Several family meetings occurred, and working with the palliative care team, a decision was made to stop aggressive treatments. A fentanyl drip was started at 2 mg/hr, and all JE’s vasoactive agents were stopped and ICD therapies deactivated. Within minutes, JE had chest pain, which diminished after he received further fentanyl. His opiate drip was gradually titrated until his chest pain was relieved. JE died 4 hours later.17

Palliative care relieves suffering and improves quality of life for patients with advanced illness and their families. Unlike hospice care, palliative care can be provided simultaneously with appropriate life-prolonging therapies.49 Most U.S. hospitals have some form of a palliative care program.50 Because changing or deactivating device settings can result in gradual worsening of chronic symptoms or onset of new symptoms, it may be helpful to involve palliative care in the care of patients before devices settings are altered, because these concerns can often be eliminated with early symptoms assessment and treatment. In addition to symptom management, palliative care clinicians are experts at complex conversations surrounding progressive illness. Their involvement in discussions about CIEDs helps to ensure that the patient and family have the opportunity to understand fully the nuances of these decisions and the implications for device management for the patient. Studies show that patients who receive palliative

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SECTION 4  Follow-up and Programming

care are more likely to have their treatment wishes followed and have better QOL at the end of life.34 Palliative care also plays a key role in supporting families of patients with advanced disease, who themselves undergo declines in physical and mental health and have an increased risk of death compared with nonfamily controls.51-53 Discussions about deactivation may be misconstrued by patients and families as the beginning of abandonment. They must understand that even if they choose to deactivate the device, the clinicians involved in their care will continue to work with them to ensure that their needs (physical and otherwise) are met. Palliative care can assist with safe and seamless transitions from one system of care to another. Hospice care is provided to patients with a prognosis of 6 months or less to live who have decided to forgo all treatments aimed at curing their underlying terminal illness.54 Hospice clinicians should be included in conversations for patients as they near the end of life to ensure continuity in implementing the goals of care regarding a CIED. Currently, most hospices do not have practices in place to ensure that these conversations occur at enrollment. Both specialists and generalists must partner with hospices to facilitate these conversations and ensure the availability of clinicians who can deactivate CIEDs for patients near the end of life. Further, both hospice and palliative care clinicians can help clarify concerns and misperceptions about the device after the patient has died. For example, some families have erroneous concerns that they may be shocked by touching their deceased relative, or that the device must be explanted after death (which is only true in the case of cremation). Likewise, the clinician can dispel the myth that continued pacemaker function after a patient has died is unnecessarily prolonging life, or even that the impulses from the device are capturing or affecting the heart in some way. IMPROVING COMMUNICATION ABOUT END-OF-LIFE CARE: IMPORTANCE OF EDUCATION To improve communication about device management for patients with advanced disease, educational endeavors need to be instituted for both health care professionals and trainees. Ongoing education for clinicians in practice, including physicians, nurses, social workers, clergy, and device manufacturer representatives, should incorporate teaching about the importance of conversations on device management to improve communication skills and create practice change. Training programs for health care professionals have been shown to improve their knowledge and increase the likelihood they will put new skills into practice.55-57 In addition, fellows and other clinicians in training must also learn the importance of these conversations, as well as undergo training specifically aimed at improving skills in communication. Senior health care providers modeling these conversations for learners are key to improving trainee education about these complex discussions.

Logistics of CIED Deactivation On notification by the patient or a health care provider, the patient’s attending physician then assumes responsibility for addressing the request, counseling the patient, and making a written order in the patient’s medical record. In many cases the attending physician will require consultation with the patient’s cardiologist or cardiac electrophysiologist to determine the specific CIED therapies that are to be deactivated. These specifics should be a part of the written order. Although the nuances of medical practice require a tailored approach to each patient, HRS recommends that the following series of procedures be consistently applied4: 1. Confirming mental capacity requirements to make the decision to withdraw CIED support. The responsible clinician should assess whether the patient or surrogate adequately understands the facts of the patient’s medical condition and the likely consequences of withdrawal of therapy, and that the patient is free of coercion by others. Accurately gauging

patient understanding in this context requires that the responsible clinician be qualified to discuss in detail the benefits and any potential negative effects of ongoing device therapy. Depending on the clinical context, this may require consultation with a clinical electrophysiologist, if one is not already directly involved in the patient’s care. Patients who have psychological or cognitive problems that may benefit from counseling or pharmacologic therapies should have these addressed before deactivation proceeds. 2. Identifying the legal surrogate if the patient lacks capacity. 3. Ensuring documentation requirements for withdrawing or withholding a CIED. Deactivation of CIED therapies requires a written order from the attending physician. This should preferably precede deactivation. In emergent situations, a verbal order should be followed by written documentation within 24 hours. The person responsible for ordering device deactivation may be the patient’s primary care physician, cardiologist, cardiac electrophysiologist, a hospitalist, or a palliative care specialist. Any of these specialists may be the most appropriate physician for such an order, although collaboration among the patient’s physicians is ideal. The written documentation in the medical record needs to address the following: a. Confirmation that the patient (or legal surrogate) has requested device deactivation. b. Capacity of the patient to make the decision, or identification of the appropriate surrogate. c. Confirmation that alternative therapies have been discussed, if relevant. d. Confirmation that consequences of deactivation have been discussed. e. Specific device therapies to be deactivated. f. Notification of family if consistent with patient’s wishes. 4. Establishing palliative care interventions and providing patient and family support. For patients at the end of life, device deactivation should be viewed as one of many potential interventions aimed at preventing discomfort or prolonged suffering. Patients must also be offered the full range of palliative measures to treat symptoms associated with the progression of their underlying illness, especially any new symptoms that may emerge from cessation of device therapy. To allow the patient to experience these symptoms without sedation or analgesia is contrary to humane end-of-life care. Clinical care of patients with arrhythmias does not end with device deactivation, and patients may benefit significantly from pharmacologic measures that minimize symptoms. In addition, the families of patients may often require considerable emotional support, especially if they have acted as the patient’s decision-making surrogate. Setting expectations for family members regarding the consequences and uncertainties of deactivation is imperative. It may be especially important to have a member of the clergy present for patients with a well-defined faith tradition. Formal consultation with palliative care experts is available in most hospital settings and frequently in long-term care facilities or other nonhospital care settings. This may be particularly appropriate when there is any uncertainty about symptom management before and after device deactivation. It is generally appropriate to discontinue rhythm monitoring when pacing therapy is withdrawn. 5. Knowing how to deactivate the device. Deactivation should be performed whenever possible by individuals with EP expertise, such as physicians or device clinic nurses or technicians. In situations where this expertise is not available (see later), deactivation should be performed by medical personnel, such as a hospice physician or nurse, with guidance from IEAPs.58 Pacing therapy, given the caveats indicated for a pacemakerdependent patient, may be withdrawn by programming to specific modes (OOO, ODO, or OSO). If such modes are not available for the device in question, the rate can be lowered and the output adjusted to subthreshold levels so as to render the pacemaker nonfunctional. Deactivation of shocking and ATP functions in an ICD



35  Ethical Issues may be accomplished by reprogramming of the device or continuous application of a magnet over certain pulse generators. Notably, there may be differences in the response to magnet application among different manufacturers’ devices and individual device programmed features. This further emphasizes the importance of consulting individuals with EP expertise to ensure that the process is as smooth as possible. Since the most urgent need for deactivation of CIEDs is the situation of repetitive ICD shocks, the recent HRS statement on deactivation suggests that, for patients who are diagnosed with a terminal illness, consideration should be given to providing them with a doughnut magnet and that they be given detailed instructions on its use.4 Application of a magnet over ICDs usually will temporarily suspend antitachycardia therapies while not disabling bradycardia pacing functions. However, it should be emphasized that although ICD shocks may be very painful and frightening, they may be lifesaving; therefore, deactivation of the device may not be warranted even in the presence of repetitive shocks, unless the patient has made the decision to forego further device therapies.

ROLE OF INDUSTRY-EMPLOYED ALLIED PROFESSIONAL In many situations, IEAPs may be asked to assist available medical personnel in deactivation when EP expertise is not available. The role of the IEAP is to provide technical assistance to medical personnel,58 who will then perform actual deactivation. Available data from a survey of HRS members and IEAPs suggests that IEAPs perform deactivation 50% of the time,2 the recent HRS statement on deactivation recommends that the IEAP should always act under direct supervision of medical personnel.4 IEAPs experience significant role conflicts when asked to perform clinical functions, in particular device deactivation,59 as illustrated by the following quotes from IEAP interviews59: I never physically ever hit the program button. I will set it all up, and then I will have someone hit it … if that makes me sleep at night, maybe that is what it is. The first time I ever had to do it, I was fine until I walked to my car and thought, ‘Oh my God.’ I just lost it when it was over with. Everyone has got their war story … where they almost couldn’t be professional about it or they almost couldn’t do their job. Most IEAPs are comfortable deactivating all ICDs, but many are not in the case of pacemakers. Clinicians must provide medical supervision to IEAPs in performance of device deactivation. Each manufacturer has policies for their personnel that apply to deactivation of CIED therapies, and it is the responsibility of IEAPs to ensure adherence to these policies. If the representative is asked by the patient and the attending physician to deactivate therapies that conflict with the policies of the company, the IEAP has the right to object to programming of the device. In this situation the attending physician assumes responsibility to find another mechanism for device programming, usually by contacting the physician who implanted or who follows the patient’s CIED. Communication with IEAPs by medical personnel at the scene, as well as physicians with EP expertise, needs to include specific instructions regarding features to deactivate, as well as information about the patient’s overall goals. Indeed, once the IEAP has a better understanding of the purpose of changing a device’s settings, the representative may be able to provide suggestions or clarify misperceptions. IEAPs stress this in interviews: “[Clinicians] should not say, ‘Turn off device,’ but they should say, ‘Disable or turn off—discontinue all tachyarrhythmia therapies. …”59 CONSIDERATIONS IN SPECIFIC CLINICAL SETTINGS How the request for deactivation is handled and who will perform deactivation often depends on the setting: (1) acute care hospital with EP expertise, (2) acute care hospital without EP expertise or

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nonhospital health-care facility, (3) at home. For each of these settings, the initial steps previously described are the same. Acute Care Hospital with Electrophysiologic Expertise For patients who are hospitalized in a center with EP expertise at the time that deactivation of the CIED is requested, their attending physician should arrange for a cardiac electrophysiologist or other clinician with expertise in CIED programming to perform deactivation. An order is documented in the chart by the attending physician that precisely specifies which CIED therapies are to be deactivated (bradycardia pacing, cardiac resynchronization pacing, ATP, or ICD shocks). The cardiologist, cardiac electrophysiologist, or their trained designee would then program the CIED in accordance with the order and should document the programming in the patient’s medical record. Inpatient Facilities Without Electrophysiologic Expertise For patients at a hospital, hospice, or long-term care facility without EP expertise, the attending physician should contact the physician responsible for following the patient’s CIED for consultation as to which therapies should be deactivated. For patients who are able to be discharged and are well enough to travel to a clinic with programming capability, an outpatient visit may be acceptable for device deactivation. However, because deactivation of therapies may be followed by the patient’s rapid demise, such as deactivation of pacing therapy in a dependent patient, clinic setting may not always be appropriate. For patients who are unable to travel, the attending physician should arrange for a programmer to be brought to the patient. This may require the assistance of a physician who follows CIED patients. In many cases, IEAPs who represent the specific manufacturer of the patient’s CIED will be asked to bring a programmer to the patient’s bedside. Medical personnel (ideally the attending physician) would deactivate the CIED using the programmer, with technical assistance provided by the IEAP. Patients at Home Patients who are at home on notifying their physician of their request for CIED deactivation may present logistical challenges. For patients who are too ill to travel to a clinic or in whom deactivation would result in rapid demise, arrangements must be made for a programmer to be brought to their home by medical personnel or IEAP. The attending physician should write an order in the patient’s medical record, including specific therapies to be deactivated. This information must be communicated to the on-site personnel, preferable in written/faxed format, unless the urgency of the situation requires verbal communication. An IEAP then should be provided to assist the physician’s clinical designee (e.g., visiting nurse, home hospice personnel) with the programmer and provide the technical assistance necessary to deactivate the specific therapies requested. If no medical personnel can be arranged, in rare cases the IEAP may be asked to perform deactivation after appropriate communication with and documentation by the attending physician. In situations where the requested deactivation is not in keeping with the manufacturer’s policies, the attending physician assumes responsibility for resolving this conflict. This may involve further consultation with a physician who has expertise in CIED therapy.

Device Deactivation in the Pediatric Patient A full discussion of end-of-life issues in minors is beyond the scope of this chapter. However, patients age 24 or under account for 1% to 2% of device implants,60 and it should be recognized that there will be unique situations where quality survival may be unattainable even for a child, and a “good death”61 may be the more appropriate goal. Two major questions may arise when one is considering forgoing lifesustaining treatment for a seriously ill juvenile patient: should the young person be informed about the gravity of his illness? And if so,

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to what extent should that young person participate in the end-of-life decision? Management of CIEDs in children nearing end of life or requesting withdrawal of treatment requires an assessment of the child’s decision-making capacity. Whether or not the child has capacity, communication of decisions should be provided to the child, recognizing developmental level and individual preferences. An ongoing dialogue is required with the juvenile patient, in which his or her concerns are probed and assurance is given that any questions about the illness and its treatment will be answered truthfully. If a child does not have decision-making capacity, a parent or guardian should make decisions in the child’s best interest. (See also Chapter 18.)

Withholding Device Therapy A second, less frequently-discussed ethical aspect of device therapy lies in the decision to withhold this therapy from a patient who may not benefit or in whom benefit is less clear. The ACC/AHA guidelines for device-based therapy clearly state that “recommendations for consideration of ICD therapy, particularly those for primary prevention, apply only to patients who … have a reasonable expectation of survival with a good functional status for more than one year.”43 However, as recently described by Beauregard,62 palliative care experts may be

consulted regarding device deactivation in patients with more recent implants. How often this occurs and why are unknown. The question has been raised whether implanting electrophysiologists may ignore severe comorbidities that might limit the benefit of ICDs.62 However, in one reported series of patients requesting deactivation, the three patients diagnosed with malignancy before device implant had all been given life expectancy of longer than 1 year by their oncologist.63 Ethics requires that physicians not impose on patients therapies that may be medically futile, as outlined by the AMA Code of Ethics.8 However, “medical futility” may be difficult to determine. A “reasonable expectation of survival for more than one year,” a relatively “hard” endpoint, can already be difficult to predict in many cases; “reasonable expectation of survival with good functional status” is even more difficult to define. To prevent the situation of device implantation in individuals who may shortly be requesting deactivation, it is important first for the physician to weigh carefully the ICD benefit in the context of the patient’s overall medical condition. Also, similar to deactivation discussions, discussions about initial implant should also follow patientcentered, “shared decision-making” models.64 Especially in older individuals, discussion of ICD implantation should focus on overall goals of care for a patient’s remaining years.

REFERENCES 1. Goldstein NE, Lampert R, Bradley E, et al: Management of implantable cardioverter-defibrillators in end-of-life care. Ann Intern Med 141:835-838, 2004. 2. Mueller PS, Jenkins SM, Bramstedt KA, Hayes DL: Deactivating implanted cardiac devices in terminally ill patients: practices and attitudes. Pacing Clin Electrophysiol 31:560-568, 2008. 3. Goldstein N, Bradley E, Zeidman J, et al: Barriers to conversations about deactivation of implantable defibrillators in seriously ill patients: results of a nationwide survey comparing cardiology specialists to primary care physicians. J Am Coll Cardiol. 54:371373, 2009. 4. Lampert R, Hayes DL, Annas GJ, et al: Heart Rhythm Society Expert Consensus Statement on the management of cardiovascular implantable electronic devices (CIEDs) in patients nearing end of life or requesting withdrawal of therapy. Heart Rhythm 7:1008-1026, 2010. 5. Beauchamp TL: Principles of biomedical ethics, ed 6, New York, 2009, Oxford University Press. 6. Annas GJ: The rights of patients: the authoritative ACLU guide to the rights of patients, ed 3, New York, 2004, New York University Press. 7. Snyder L, Leffler C: Ethics manual, fifth edition. Ann Intern Med 142:560-582, 2005. 8. American Medical Association Council on Ethical and Judicial Affairs. AMA 2008–2009. Code of Medical Ethics: current opinions and annotations. Chicago, 2010, AMA Press. 9. Pellegrino ED: Decisions to withdraw life-sustaining treatment: a moral algorithm. JAMA 283:1065-1067, 2000. 10. Rhymes JA, McCullough LB, Luchi RJ, et al: Withdrawing very low-burden interventions in chronically ill patients. JAMA 283:1061-1063, 2000. 11. Quill TE, Barold SS, Sussman BL: Discontinuing an implantable cardioverter-defibrillator as a life-sustaining treatment. Am J Cardiol 74:205-207, 1994. 12. In re Quinlan. 70 N.J. 10, 355 A.2d 647 New Jersey Supreme Court. 1976. 13. Cruzan v. Director Missouri Department of Health. 497 U.S. 261 88-1503, 1990. 14. Annas GJ: “Culture of life” politics at the bedside—the case of Terri Schiavo. N Engl J Med 352:1710-1715, 2005. 15. Burt RA: Death is that man taking names, Berkeley, 2002, University of California Press. 16. Schneider C: The practice of autonomy: patients, doctors, and medical decisions, New York, 1998, Oxford University Press. 17. Wiegand DL, Kalowes PG: Withdrawal of cardiac medications and devices. AACN Adv Crit Care 18:415-425, 2007. 18. Belcherton State School v. Saikewicz. 370 N.E. 2d. 417, 1977. 19. Kay GN, Bittner GT: Should implantable cardioverterdefibrillators and permanent pacemakers in patients with terminal illness be deactivated? Deactivating implantable cardioverter-defibrillators and permanent pacemakers in patients with terminal illness: an ethical distinction. Circ Arrhythmia Electrophysiol 2:336-339, 2009. 20. Meisel A, Snyder L, Quill T, American College of Physicians– American Society of Internal Medicine End-of-Life Care Consensus: Seven legal barriers to end-of-life care: myths, realities, and grains of truth. JAMA 284:2495-2501, 2000. 21. Vacco v. Quill. 521 U.S. 793, 95-1858. Supreme Court of the United States, 1997. 22. Washington v. Glucksberg. 521 U.S. 702, 96-110. Supreme Court of the United States, 1997.

23. Sulmasy DP: Within you/without you: biotechnology, ontology, and ethics. J Gen Intern Med 1:69-72, 2008. 24. Zellner RA, Aulisio MP, Lewis WR: Deactivating permanent pacemakers in patients with terminal illness; patient autonomy is paramount. Circ Arrhythmia Electrophysiol 2:340-344, 2009. 25. Swetz KM, Crowley ME, Hook C, Mueller PS: Report of 255 clinical ethics consultations and review of the literature. Mayo Clin Proc 82:686-691, 2007. 26. The Joint Commission. Joint Commission Requirements, 2010. 27. PSDA-90. Ominbus Budget Reconciliation Act of 1990. [Patient Self-Determination Act of 1990]. Pub. L. 101–508, 4206, and 4751. (Medicare and Medicaid, respectively), 42 U.S.C. 1395cc(a) (I) (Q), 1395 mm (c) (8), 1395cc(f), 1396(a)(57), 1396a(a) (58), and 1396a(w) (Suppl 1991). U S, 2010. 28. Braun TC, Hagen NA, Hatfield RE, Wyse DG: Cardiac pacemakers and implantable defibrillators in terminal care. J Pain Symptom Manage 18:126-131, 1999. 29. AMA Council on Ethical and Judicial Affairs: Physician objection to treatment and individual patient discrimination: CEJA Report 6-A-07, Chicago, 2007, AMA Press. 30. May T: Bioethics in a liberal society, Baltimore, 2002, Johns Hopkins University Press. 31. Goldstein NE, Mehta D, Teitelbaum E, et al: “It’s like crossing a bridge”: complexities preventing physicians from discussing deactivation of implantable defibrillators at the end of life. J Gen Intern Med 1:2-6, 2008. 32. Fried TR, Bradley EH, Towle VR, Allore H: Understanding the treatment preferences of seriously ill patients. N Engl J Med 346:1061-1066, 2002. 33. Fried TR, Byers AL, Gallo WT, et al: Prospective study of health status preferences and changes in preferences over time in older adults. Arch Intern Med 166:890-895, 2006. 34. Wright AA, Zhang B, Ray A, et al: Associations between end-oflife discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA 300:1665-1673, 2008. 35. Lewis WR, Luebke DL, Johnson NJ, et al: Withdrawing implantable defibrillator shock therapy in terminally ill patients. Am J Med 119:892-896, 2006. 36. Singer PA, Martin DK, Kelner M: Quality end-of-life care: patients’ perspectives. JAMA 281:163-181, 1999. 37. Nicolasora N, Pannala R, Mountantonakis S, et al: If asked, hospitalized patients will choose whether to receive life-sustaining therapies. J Hosp Med 1:161-167, 2006. 38. Fried TR, O’Leary JR: Using the experiences of bereaved caregivers to inform patient- and caregiver-centered advance care planning. J Gen Intern Med 23:1602-1607, 2008. 39. Berger JT, Gorski M, Cohen T: Advance health planning and treatment preferences among recipients of implantable cardioverter-defibrillators: an exploratory study. J Clin Ethics 17:72-78, 2006. 40. Goldstein NE, Mehta D, Siddiqui S, et al: “That’s like an act of suicide”: patients’ attitudes toward deactivation of implantable defibrillators. J Gen Intern Med 1:7-12, 2008. 41. Goldstein NE, Back AL, Morrison RS: Titrating guidance: a model to guide physicians in assisting patients and family members who are facing complex decisions. Arch Intern Med 168:1733-1739, 2008. 42. Covinsky KE, Goldman L, Cook EF, et al: The impact of serious illness on patients’ families. SUPPORT Investigators. Study to

Understand Prognoses and Preferences for Outcomes and Risks of Treatment. JAMA 272:1839-1844, 1994. 43. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation 117:e350-e408, 2008. 44. Schoenfeld MH: Follow-up assessments of the pacemaker patient. In Ellenbogen KA, Wood MA, editors: Cardiac pacing and ICDs, ed 5, Hoboken, NJ, 2008, Wiley-Blackwell, pp 498-545. 45. Schoenfeld MH: Deciding against defibrillator replacement: second-guessing the past? Pacing Clin Electrophysiol 23:20192021, 2000. 46. Wilkoff BL, Auricchio A, Brugada J, et al: Heart Rhythm Society, European Heart Rhythm Association, American College of Cardiology, American Heart Association, European Society of Cardiology Heart Failure Association, Heart Failure Society of America. HRS/EHRA expert consensus on the monitoring of cardiovascular implantable electronic devices (CIEDs): description of techniques, indications, personnel, frequency and ethical considerations. Heart Rhythm 5:907-925, 2008. 47. Emanuel EJ, Fairclough DL, Slutsman J, et al: Assistance from family members, friends, paid care givers, and volunteers in the care of terminally ill patients. N Engl J Med 341:956-963, 1999. 48. Lynn J, Goldstein NE: Advance care planning for fatal chronic illness: avoiding commonplace errors and unwarranted suffering. Ann Intern Med 138:812-818, 2003. 49. Morrison RS, Meier DE: Clinical practice: palliative care. N Engl J Med 350:2582-2590, 2004. 50. Goldsmith B, Dietrich J, Du Q, Morrison RS: Variability in access to hospital palliative care in the United States. J Palliat Med 11:1094-1102, 2008. 51. Schulz R, Beach SR: Caregiving as a risk factor for mortality: the Caregiver Health Effects Study. JAMA 282:2215-2219, 1999. 52. Schulz R, Newsom J, Mittelmark M, et al: Health effects of caregiving: the Caregiver Health Effects Study: an ancillary study of the Cardiovascular Health Study. Ann Behav Med 19:110-116, 1997. 53. Lee S, Colditz GA, Berkman LF, Kawachi I: Caregiving and risk of coronary heart disease in U.S. women: a prospective study. Am J Prev Med 24:113-119, 2003. 54. National Consensus Project for Quality Palliative Care: Clinical practice guidelines for quality palliative care, 2009. 55. Ersek M, Grant MM, Kraybill BM: Enhancing end-of-life care in nursing homes: Palliative Care Educational Resource Team (PERT) program. J Palliat Med 8:556-566, 2005. 56. Robinson K, Sutton S, von Gunten CF, et al: Assessment of the Education for Physicians on End-of-Life Care (EPEC) Project. J Palliat Med 7:637-645, 2004. 57. Unutzer J, Katon W, Callahan CM, et al: Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. Treatment IIIM-PAtC. JAMA 288:2836-2845, 2002. 58. Lindsay BD, Estes NA, 3rd, Maloney JD, et al: Heart Rhythm Society policy statement update: recommendations on the role of industry-employed allied professionals (IEAPs). Heart Rhythm 5, 2008.



59. Mueller PS, Ottenberg AL, Hayes DL: Role conflicts among industry employed allied professionals: characteristics and recommendations for addressing them. Heart Rhythm 7:S11, 2010. 60. Zhan C, Baine WB, Sedrakyan A, Steiner C: Cardiac device implantation in the United States from 1997 through 2004: a population-based analysis. J Gen Intern Med 1:13-19, 2008.

35  Ethical Issues 61. Baines P: Medical ethics for children: applying the four principles to paediatrics. J Med Ethics 34:141-145, 2008. 62. Beauregard L: Ethics in electrophysiology: a complaint from palliative care. Pacing Clin Electrophysiol 33:226-267, 2010.

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63. Kobza R, Erne P: End-of-life decisions in patients with malignant tumors. Pacing Clin Electrophysiol 30:845-849, 2007. 64. Mead N, Bower P: Patient-centredness: a conceptual framework and review of the empirical literature. Soc Sci Med 51:1087-1110, 2000.

Acute myocardial infarction (Continued)

Acute myocardial infarction (Continued)

INDEX

Acute myocardial infarction (Continued)

Page numbers followed by f indicate figures; t, tables; b, text in boxes.

A AAI atrial hysteresis, timing interval for, 816f AAI mode atrial refractory period, timing interval for, 816f AAI mode blanking period, timing interval for, 816f AAI pacing, 223-224. See also Atrial pacing contraindications for, 320t hypertrophic obstructive cardiomyopathy during, 229f pacemaker syndrome during, 227-228 refractory period for, 400f timing interval for, 815-816, 815f-816f ventricular tachycardia during, 319f AAIR pacing contraindications for, 320t managed ventricular pacing and AVB during exercise, 351f criteria for switching, 351f pacemaker syndrome during, 227-228 refractory period for, 400 sinus node disease and, 318-320 AAI(R) pacing mode, MVP algorithm and, 833-834 AAI(R)-to-DDDR mode switching, 833-834, 834f AAIR vs. AAI/VVI, 156 AAIsafeR mode, 316-317, 834-835 AAT pacing mode, 836 Abdominal pacemaker, radiography of, 773f-774f Abdominal pocket, for ICD, 496, 496f Absolute risk reduction, for sudden cardiac death, 260 Accelerometer, 146 monitoring walking distance, 159f Accelerometer-based pacemaker, 147-149 Acoustic energy, 435-439 Acoustic radiation, 1005 Acoustic window, 437, 437f Acquired AV block causes of, 333-336, 333t permanent pacing for, 337t Action potential, 7 fibrillation and, 41 from heart cells, 9f secondary source model for, 46 Action potential duration (APD) diastolic interval and, 41 restitution relationship of, 41f Activation polarization, 177 Active discrimination, 101 Active-fixation electrode acute endocardial placement of, 411f chronic long-term thresholds for, 408f Active-fixation helix, 127, 133f in epicardial active-fixation steroid-eluting lead, 135f Active-fixation lead in atrium, advantages of, 475 in coronary venous system, 135-136, 136f current of injury and, 476 dexamethasone-eluting reservoir in, 133f

Active-fixation screw, positioning of, 783f, 791 Active screw-in, sensing and, 58 Activity of daily living programming, 147 Activity sensing, 145-146 Activity-sensing device limitations of, 149 types of, 147-148 Activity-sensing pacemaker, 147f types of, 147-149 Activity sensor, 145-146 clinical results of, 148-149 types of, 147f Acuity Spiral LV lead, 598-600 in target vein, 599f Acuity Steerable LV lead, 598 in target vein, 599f Acute atrial epicardial electrode threshold, 406f Acute care hospital with electrophysiologic expertise, device deactivation and, 1047 Acute decompensated heart failure (ADHF), 156-157 hospitalization for, 167f, 999 symptoms, signs, and investigations, limitations of, 157-158 triggers of, 156-157 Acute myocardial infarction anterior or anteroseptal, effects of, 338, 339t atrioventricular block and, 338 with BBB, 339-341, 340t without BBB, 338, 339t AV node conduction disturbances during, 323 bundle branch block in, 340t electrocardiogram of, 341f mortality and sudden death rate, 341 high-grade AV block and, 340f BBB after recovery, 343 inferior or posterior, effects of, 338, 339t occurrence of, 338 onset of, 338 pacing in permanent, 345-346, 345t temporary, 344-345 thrombolytic therapy for, 341-343 Adapter categories of, 734 older models of, 733f pocket bulk from, 736f Adaptive-rate pacing, 825-827 Advanced Elements of Pacing Randomized Controlled Trial (ADEPT), 236-237 Advisory notice. See Product advisory Air embolism prevention of, 467b risk of, 466 Alignment error, 90, 92f Alternans Before Cardioverter-Defibrillator (ABCD) observational study, 272 Alternative medicine device, electromagnetic interference and, 1013 Alternative-ventricular site pacing, 801-803 ALTITUDE study, 296

Aluminum electrolytic capacitor components of, 187 cutaway view of, 188f photomicrograph of, 187f Ambulatory electrocardiographic monitoring, 414-415 Ambulatory failure, 448 Ambulatory pacemaker implantation, 448-449 analysis of, 448t protocol for, 448b Ambulatory surgery, definition of, 448 American College of Cardiology/American Heart Association AV block risks, pacemaker recommendations on, 328 cardiac channelopathy risk stratification/ treatment guidelines, 385 ICD and CRT implantation guidelines and, 491-492 ICD therapy recommendations by, 273t pacing mode selection guidelines, 253 Aminophylline, 338 Amiodarone, defibrillation threshold and, 907f Amiodarone versus Implantable CardioverterDefibrillator Trial (AMIOVIRT) for ICD therapy, 266 criteria, comparison groups and results, 264t population details/mortality results, 265t Ampere-hour, 176 Amplatz Goose Neck, 761, 763f Amplitude, 56-59 of electrogram, 58 exercise effect on, 58 during retrograde atrial activation, 58-59 undersensing and, 58 Amplitude Safety Margin, LVCM and, 927 Anchor balloon technique, 558 coronary sinus cannulation with, 693 for coronary sinus cannulation, 697f coronary sinus recovery using, 694-695 equipment for, 697b Andersen-Tawil syndrome, 332 Anesthesia general endotracheal, 754 for lead extraction, 754 for pacemaker implantation, 452 types of, 452t Anesthetist, for pacemaker implantation, 444 Angel Med Guardian, 170, 170f Angioplasty, of collateral vein, 677f, 682f Angioplasty balloon, 623-625 rupture of, 687f Angioplasty wire, 631f, 699, 700f coronary balloon and delivery guide, loading, 696f Anisotropy ratio, 47 Anodal capture, 924 ventricular activation sequence, effect of, 925f Anodal shock, 376-377 Anodal stimulation, 11-13 action potential initiation by, 12f

1051

1052

Index

Anodal stimulation (Continued) cathodal stimulation versus, 23 tachyarrhythmias, generation of, 23 threshold at coupling intervals, 23, 23f Anode, 4 batteries and, 175, 176f corrosion of, 23 definition of, 175 resistance of, 16 Anode break computer simulation of, 12f occurrence of, 12f Anode make computer simulation of, 12f effects of, 11-12 Anterior septum, contraction patterns in, 209f Anterior subpectoralis muscle approach, for ICD implantation, 502f Anterolateral chest, anatomy of, 454f Antiarrhythmic drug, stimulation threshold and, 32 Antiarrhythmic versus Implantable Defibrillator (AVID) trial CIDS, CASH and, pooled analysis of, 263 for ICD therapy, 261-262 criteria, comparison groups and results, 262t population details/mortality results, 262t shock incidence in, 902 Antibiotic-impregnated pouch, 738f Antibiotic prophylaxis, for infection prevention, 452-453 Antibradycardia pacing revised NASPE/BPEG generic code for, 196, 197t examples of, 198t Antibradycardia therapy, in Long QT Syndrome, 386-387 Antimicrobial irrigation protocol, 453t Antishoplifting gate, electromagnetic interference and, 1012 Antitachycardia device, oversensing in, 722f Antitachycardia pacing advantage of, 380 burst versus ramp, 379-380 in children, 421 electrode placement/selection, 421 indications for, 83, 379-380 problems with, 907-908, 908t stimulation threshold and, 15 VT shock therapy and, 904 Antitheft device, electromagnetic interference and, 1012 AOO pacing mode, 836 Aortic pressure tracings, in heart failure patient, 217f Aortic velocity time interval by ECG method versus EGM-based method QuickOpt, 967f pacemaker AVI change effect on, 926 semi-automatic adjustment of, 968 Arrhythmia atrial electrogram during, 58-59 detection of, 56 event notification for, 999 failure to convert, cause of, 904-905 Arrhythmogenic right ventricular dysplasia (ARVD) computed tomography and, 808 magnetic resonance imaging and, 808

Artificial electrical stimulation, of cardiac tissue, 8-13 Ascorbic acid, 622 Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients, 314 Asynchronous activation, 209-210 Asynchronous heart failure, cause of, 913-915 Asynchronous LV contraction, hemodynamic consequences of, 913 Asynchronous pacing mode, AOO, VOO, DOO, 836 Asynchronous ventricular activation, 914f Asynchrony, 913 Atonic stage, of ventricular fibrillation, 41f development of, 40 Atrial activation/contraction, 205 Atrial activation time (AAT), 949-950 analysis of, 951f Atrial antiarrhythmic pacemaker, diagnostic data stored in, 115f Atrial antitachycardia pacemaker, SVT-VT detection and, 112-116 Atrial antitachycardia pacing therapy, 311f atrial fibrillation frequency and, 312f median AT/AF burden before and after, 312f at baseline and years after, 312f Atrial arrhythmia cause of, 880 detection of, 902 Atrial-based timing, 823-825 Atrial-based timing cycle, 829f Atrial-based timing pacemaker, prolongation of AEI in, 829f Atrial blanking period, 815f Atrial capture latency, 949 Atrial capture management, 79, 84f Atrial Capture Management feature, 34 Atrial coupling, atrial fibrillation disrupting, 911 Atrial desynchronization, 911-915 Atrial/dual-chamber pacing, ventricular single-chamber pacing versus, 238-239 Atrial Dynamic Overdrive Pacing Trial (ADOPT), 310 AF suppression and, 832 Atrial electrode, placement of, 475f atrial positioning for, 475, 475f techniques for, 474-476, 475f using straight/non-preformed lead, 475 through persistent left superior vena cava, 489f Atrial electrogram (AEGM), 86f-87f amplitude of, 56 during arrhythmias, 58-59 during atrial fibrillation, 58-59 atrioventricular pacing and, 216f exercise effect on, 58 in heart failure patient, 217f high-rate episodes on, 857f respiratory variation in, 58 Atrial endocardial electrogram, 61f Atrial epicardial electrode implantation, 405 Atrial escape interval (AEI), 823-824, 824f prolongation in atrial-based timing pacemaker, 829f Atrial fibrillation. See also Atrial antitachycardia pacing therapy atrial coupling, disruption of, 911

Atrial fibrillation (Continued) atrial/dual-chamber pacing versus ventricular single-chamber pacing, 239 atrial electrogram during, 58-59 atrial flutter, organizing into, 311f atrial pacing causing, 833 cardiac desynchronization caused by, 972f CIEDs and, 858 complete heart block and, 326 detection of, 306-307 algorithm for, 120f for atrial therapy, 114-115 factors influencing, 307t principles of, 114 frequency in, 312f Holter recording of, 117f home monitoring for, 994f hospitalization for, 307f inappropriate detection of, 100f inappropriate shocks for, 389f monitoring for, 114 multiple shocks and, 902, 903f pacing algorithms in prevention of, 308-311 in termination of, 311-312 pacing mode and, 246f, 306-313 impact on, 307t in prevention of, 307-308 RCT for, 244f, 246 pacing mode and mortality, studies on, 239t postshock early recurrence of, 119f prevention of, 832-833 right ventricular apical pacing and, 503 site-specific pacing for prevention, 312-313 suppression algorithm for, 833f symptomatic, time spent in, 310f termination of, 118f thromboembolism risk and, 313-314 undersensing in QRS complex in, 875f ventricular pacing and, 314-315, 315f, 317-318 VVI pacing mode for, 813 Atrial fibrillation lead system, 793 radiographic view of, 796f Atrial Fibrillation Reduction Atrial Pacing Trial, 314 Atrial flutter appropriate rejection of, 101f detection algorithm for, failure of, 831f electrograms of children in, 415f mode switching during, 830-831 algorithms for, 831, 831f organizing into from AF, 311f Atrial high rate episode (AHRE), 159-160 Atrial ICD atrial sensing in, 67 SVT-VT detection and, 112-116 Atrial lead with fracture/protrusion, 794f lead dislodgment with, 483 positioning of, 312-313, 313f radiography of, 780-781 in RA appendage, 784f Atrial muscle, action potential of, 9f Atrial natriuretic factor (ANF), 205-206 Atrial oversensing, 970-971 Atrial pacing (AAI). See also AAI pacing for AF prevention, 312-313 atrial fibrillation and, 833



Atrial pacing (Continued) cardiac output versus mean atrial pressure during, 209f competitive versus noncompetitive, 833 DDD pacing versus, 243 clinical events in, 244t electrogram method and, 950f hemodynamic effects of, 210f optimal pacemaker AVI during, 953f pacemaker AVI interaction with, 949-952 for stressing His-Purkinje system, 328 ventricular pacing versus, meta-analysis of, 243 for ventricular synchrony, 218 Atrial pacing preference (APP), 832 Atrial pressure, atrial pacing and, 209f Atrial proarrhythmia, 105f Atrial rate dual-chamber rhythm classification and, 96f ventricular rate versus, 95 Atrial refractory period AAI mode, 816f hysteresis and, 815-816 Atrial sensing, 223-224 in dual-chamber and atrial ICDs, 67 electrogram method and, 950f far-field R wave rejection by, 71f loss of, 64f optimal pacemaker AVI during, 953f postventricular atrial blanking effect on, 69f Atrial sensitivity, mode switching and, 831f Atrial septal pacing, 509-510 selective site pacing and, 509 Atrial Septal Pacing Clinical Efficacy Trial (ASPECT), 310 Atrial shock, detection considerations for, 115-116 Atrial single-chamber pacing dual-chamber pacing versus, clinical trials for, 243-247 in sinus node disease, 237-238, 237t Atrial switch operation, 393 endocardial electrode implantation after, 412f Atrial synchronized ventricular pacing, ventricular single-chamber pacing versus, 235 Atrial tachyarrhythmia detection of, 116f pacemaker implantation and, 395 with rapid ventricular conduction, 971-973 Atrial tachycardia detection of for atrial therapy, 114-115 principles of, 114 therapy and, 118f false-positive detection of, 308f monitoring for, 114 termination of, 118f Atrial Therapy Efficacy and Safety Trial (ATTEST), 311-312 Atrial tracking, sensor-driven appearance of, 826f Atrial tracking preference (ATP), 970, 971f Atrial tracking recovery (ATR), 970f-971f CRT, minimizing loss of, 970 Atrial transport block, cause of, 943f Atrial uncoupling, 911 Atrial undersensing, 64f forms of, 968 ventricular safety pacing resulting from, 819f

Index

Atrial-ventricular activation time, by surface ECG and local EGM timing, 951, 951f Atrial vulnerable period, 830-831 Atrioventricular block acquired causes of, 333-336, 333t permanent pacing for, 337t acute myocardial infarction and, 338 with BBB, 339-341, 340t without BBB, 338, 339t in AV node, 325f cardiac pacing and, 234 cause of, 323 chronic, permanent pacing in, 337 classification of, 329 as congenital, 331-332 crosstalk and, 877f diagnosis of sites for, 325 diastolic dysfunction causing, 943-944 exercised-induced transient, 336 first-degree, 329 as high-grade definition of, 330 rhythm strip of, 330f in His-Purkinje system atropine, 326f LV cavity volume, effects on, 212f Lyme disease and, 335 mortality rates of, 342f pacing mode for selection of, 346-353 survival rate with, 239t Paroxysmal, 330-331 radial artery pressure with, 226f rhythm strips of, 325f right ventricular apical pacing in, 350 risk factors for, 328-329 second-degree, 330 single-lead VDD versus dual-chamber DDD pacing, 235 site-specific ventricular pacing for, 350-353 symptoms of, 329 syncope with incomplete RBBB, tracings from, 336f types and characteristics of, 323 type II second-degree, 325f type I second-degree, 325f vagally mediated, 336 ventricular versus “physiologic” pacing modes, 238 Atrioventricular conduction system anatomy of, 323 representative diagram of, 324f atropine improving, 325-326 diagnosis of disturbances in electrocardiography, 323-327 electrophysiologic study, 327-328 Atrioventricular conduction system disease connective tissue disorder and, 336 diagnosis, pathophysiology and prognosis for, 323-360 inherited, 332-333 Atrioventricular conduction time, 927 Atrioventricular coupling, 911 schematic representation of, 912f Atrioventricular decoupling excessively long pacemaker AVI causing, 944f schematic representation of, 912f

1053

Atrioventricular delay interval, 216f automatic rate-responsive atrioventricular delay (RAAVD), 350f exercise and activity, 215f factors influencing, 214t in long-term CRT, optimization studies, 293-294 LV outflow recording at, 214f optimization of, 225-226, 225f pacemaker syndrome and, 318 programming of hemodynamic effects of, 214f PQ interval, effect of, 215f purpose of, 214 Atrioventricular desynchronization arrhythmia, 884 Atrioventricular dyssynchrony, pacemaker syndrome and, 228-229 Atrioventricular electromechanical time, RA pacing effect on, 951-952, 952f Atrioventricular interval, 817-819 biventricular capture and, 837 determination of, 213 determining optimal, 349f hemodynamic effects of, 912f programming of, 348-350 rate-adaptive shortening/delay, 349 Atrioventricular interval hysteresis, 818-819 positive, 820f Atrioventricular interval prolongation, diagrammatic representation of, 825f Atrioventricular mechanical latency (AML), 946-947 Atrioventricular mechanics, optimal AV resynchronization and, 915 Atrioventricular nodal ablation, 335 Atrioventricular nodal cell action potential of, 9f characteristics of, 7 Atrioventricular node, 323 acute myocardial infarction and, 323 anatomy of, 323 Atrioventricular pacing, 216f hemodynamic effects of, 210f rate smoothing leading to, 842f sequential, 213 surface ECG, AEG, VEG, PCW recordings during, 216f Atrioventricular resynchronization, 947-948 approaches to comparison of, 948-949 conventional echocardiography, 944-947 optimization of, 943-944 LV inflow analysis and, 944-947 methods to guarantee, 936-938 optimal pacemaker AVI for, 948 Ritter method for, 944-945, 945f summary of, 946f using acute changes in aortic pressure, 949f using electrogram analysis, 950f using invasive hemodynamic monitoring, 947, 947f Atrioventricular search hysteresis (AVSH), 272 Atrioventricular synchronous pacing, 234 Atrioventricular synchrony, 144 importance of, 213 physiologic effects of, 211-219

1054

Index

Atrioventricular timing (AV timing) automatic adjustment of QuickOpt, 966-968 SmartDelay optimization, 963-968 Atrioventricular uncoupling, 911 Atrium active-fixation leads in, advantages of, 475 function of, 213 Atropine, AV conduction and, 325-326 Autocapture, 132f Autocapture fusion avoidance, in St. Jude Medical pacemaker, 355f Autocapture pacemaker, sense amplifier for, 353-354 Autocapture pacing advantages/benefits of, 353 adverse effects of, 353 Autocapture threshold search, 354f Automated capture feature, 34, 353 Automatic capture verification, pacing output management and, 353-355 Automatic drug delivery systems, 371 Automatic Gain Control, 65 Automaticity, cardiac action potential and, 8 Automatic mode switching (AMS), 78 in pacemaker, 830 sensitivity and specificity of, 82f Automatic pulse amplitude (APA), 34 Automatic rate-responsive atrioventricular delay (RAAVD), fixed AV delay versus, 350f Automatic remote monitoring, 989 with daily screening, 996 data transmission for, 990f speed/time for, 991f event notification, 989t follow-ups for, 998 Autosensing, for sensing safety margin, 66f Auxotonic relaxation, ventricular pacing versus sinus rhythm, 209 A-V Rate Branch, 102f Axillary approach, for ICD implantation, 501-502 Axillary-subclavian junction, high-grade stenosis of, 649f Axillary/subclavian venography, showing venous anatomy, 780f Axillary vein, 453-454 pectoralis minor muscle and, anatomic relation of, 459f ultrasonic image of, 463f Axillary vein approach, for endocardial electrode implantation, 410 Axillary venipuncture Nichalls’ landmarks for, 460f using guidewire as landmark, 484f Axillary venous access contrast venography and, 462 cutdown technique for, 462 Doppler flow detection/ultrasound techniques for, 462-463, 463f lateral access to, 463 retention wire, before/after insertion, 533f techniques for, 453b for transvenous pacemaker placement, 459-468 using first rib, 460, 462f using guidewire as landmark, 485f using J-tipped polytetrafluoroethylene guidewire, 462, 463f

Azygos vein anatomy of, 500f sheath insertion from right axillary vein, 716f Azygos vein cannulation, 712b catheter for, 712f advanced over glide wire, 713f from right side, 715f Azygos vein coil placement, 714f interventional approach to, 711-713 Azygos vein defibrillation coil, 498-499 Azygos vein defibrillation lead, 793 radiographic view of, 797f Azygos vein occlusion venography, 781f Azygos venography, 803

B Bachmann’s bundle, 509 Balanced Endless-loop tachycardia (ELT), 881 Balloon. See also Anchor balloon technique aramid fiber (Kevlar), 652f compliance of, 623-624 compliant versus noncompliant, 624f-625f types of, 623-624 coronary sinus cannulation with, 693 coronary sinus venogram, 693 diameter of, 625, 625f inflation pressure of, 625 length of, 625 long versus peripheral balloon, 651f in myocardium, inflating, 681, 690f for occlusive coronary sinus venography, 589 compliant versus noncompliant, 588-589, 589f trauma from, 588-589 over-the-wire versus monorail, 624f predilation of small vein for larger balloon, 678f profile of, 625, 625f short, total occlusion dilation with, 652f for subclavian vein venoplasty, 647-652 technique considerations for, 624 Balloon catheter, 623 Balloon venoplasty, of main coronary sinus, 664f-665f Baseline left bundle branch block, pressure-volume graphs of, 280f Baseline left bundle branch block activation, lead positions and, 936f Battery as case negative/positive, 176 charge available for, 3 charge drain from, minimizing, 16 chemistries in defibrillators, 182-183 cutaway view of, 183f chemistries in pacemakers lithium-carbon, 181-182 lithium-hybrid cathode, 182 lithium-iodine, 181, 181f classification of, 176 primary, 176 secondary, 176 components of anode and cathode, 175 electrolytes, 175-176 separator, 176 defibrillation performance, effect on, 189-190 end-of-service indication, 180-181 elective replacement indicator, 180 false triggering, 180-181 methods for monitoring, 180

Battery (Continued) functional characteristics of capacity, 176 energy and energy density, 176-177 stoichiometry and cell balance, 177 function and electrochemistry of chemical reactions, 175 energy storage, 175 generator survival code and, 396f in ICD, 183-184 lithium-layered silver vanadium oxide-carbon monofluoride, 184 lithium-manganese dioxide, 184 lithium-silver vanadium oxide (LiSVO), 183-184 impedance optimization for minimal consumption of, 22 in implantable cardiac rhythm management devices average versus instantaneous current drain, 178 design requirements for, 178 power requirements for, 178 pulse amplitude on pacing current, effect of, 179 pulse width on pacing current, effect of, 179, 179f shape, size, and mass constraints, 178 size, energy density, and current drain, 178 load voltage versus capacity plot, 177f load voltage versus current drain plot, 177f longevity of, 16 programming voltage versus pulse width for, 35, 35f measured data in, 844-846 non-ideal behavior of polarization, 177 self-discharge, 177-178 power sources for capacitors, 186-189 rechargeable lithium-ion battery, 185-186 pulse generator, longevity of, 178-179 safety concerns with, 184-185 schematic representation of, 176f sealing of, 176 Battery anode, 4 Battery cathode, 4 Battery depletion behavior during, 875 ICD follow visit and, 722 indicators of, 720, 720b mode, rate, parameter change, cause of, 866, 866b Battery discharge, monitoring, 180 Battery impedance, 180 for pacemaker, 846f Battery replacement indications for, 181 reoperation for, 729-730 Battery status indicator, 721f dataset measuring, 866-867 Battery voltage, 180 for pacemaker, 846f Beat-by-beat behavior. See Timing cycle BEST sensor, 151 tracings for, 151f Beta-2 adrenergic receptor gene transfer, biologic pacemaker and, 191



Beta-adrenergic blocker in Brugada syndrome, 390 for cardiac channelopathies CPVT, 385 Long QT Syndrome, 383-384 for vasovagal syncope, 366 BEta-blocker STrategy plus Implantable Cardioverter-Defibrillator Study (BEST-ICD) for ICD therapy, 270 criteria, comparison groups and results, 268t population details/mortality results, 269t Betacel, 434 Bezold-Jarisch reflex, 338 Bidirectional telemetry, 844 Bidomain model, 47-48 circuit diagram of, 47f Bidomain theory, 18 Bifascicular block, 326-327 chronic, permanent pacing in, 338t progression of, 331 Bilateral occlusion, lead extraction for, 751f Biologic pacemaker, 439-440 advances in development of, 320 cell therapy strategies for, 193-194 development of, 191-194 gene therapy approach to beta-2 adrenergic receptor gene transfer, 191 IF manipulations, 191-193 IK1 knockout, 191 Biomedical endocardial Sorin transducer, 151f Biotronik dual-sensor pacemaker, 153t Biotronik LV lead, 598 Biotronik SMART algorithm, 102f Biphasic stimulation energy requirements for, 26 in rabbit/frog ventricles, 26, 26f Biphasic stimulus effect, on voltage decay, 19, 19f Biphasic waveform, 42-45 charge burping theory and, 375-376, 376f definition of, 374 Bipolar electrocoagulation, 1019 Bipolar electrode system, 56 Bipolar electrogram, unipolar electrogram versus, 61f Bipolar IS-1 connector, 872f Bipolar pacing lead, 23, 127 example of, 614f stimulation threshold of, 127-128 Bipolar pacing system electrocardiogram of, 12-lead, 868f electrodes and leads in, 23 electrode sensing for, 405f implantation thresholds for, 405f unipolar pacing versus, 404-405 Bipolar split-cathodal configuration, 33 Bipolar stimulation, 23-24 Bipolar ventricular electrogram, telemetered, 853f Biventricular capture, atrioventricular interval and, 837 Biventricular cardiac resynchronization system, upgrading to, 725 Biventricular cart, 529, 530f Biventricular device, troubleshooting of, 911-986 Biventricular impedance clinical studies for, 169 intrathoracic impedance versus, 169t measurement of, 168-169

Index

Biventricular pacemaker, 219-220 upgrading to, 732-733 precautions for, 733 venous access for, 732 venous stenosis, 732-733 Biventricular pacing, 33-34, 839f atypical QRS hieroglyphic signatures during, 939f configurations for, 921f CT for patient not responding to, 808f effect on ventricular repolarization, 983f electrical activation times for RV/LV during, 223f functional conduction block line manipulation during, 955f incomplete ventricular activation fusion during, 937f increase during AT/AF caused by VRR, 977f leads and electrodes for, 922f left ventricular dysfunction and, 352-353 loss of, 840-841, 841f LV activation fusion, heterogenous effects on, 957f with LV paced event before RV sensed event, 837f percentage of, 160-161 polymorphic ventricular tachycardia during, 983f pulse generator for, 923f refractory periods and, 840 right ventricular pacing versus, trial evaluating, 252-253 with RV-based timing after atrial event, 837f competitive pacing and, 841f LV refractory extension and, 841f with RV sensed event before LV paced event, 837f sensing and, 838-841, 839f-840f sequential versus simultaneous, 963 neural effect of, 965f spontaneous/pacing-induced conduction blocks implications during, 958-959 timing cycle in, 837 goals of, 836-837 premature beats and, 840 ventricular activation wavefront fusion during, 939f at shortened AVD, 938f Biventricular pacing cable, 532f Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) study, 252, 295-296 Biventricular RV-LV interval, 838f RV sensing with, 839f Biventricular sensing pacing and, 838-841, 839f-840f response to, 838f unipolar pacing and, 840f with univentricular pacing, 839 Biventricular versus RV Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) study, 295-296, 352-353 Blanking period, 56 AAI mode, 816f in cardiac resynchronization ICDs event markers illustrating, 71f DDD atrial, 819f

1055

Blanking period (Continued) for DDD(R) pacing mode, 65f definition of, 874-875 for pacemakers and ICDs, 61 sensing and, 60 short same-chamber, 66 ventricular, 813 BLOCK-HF trial, 252 Blunt microdissection, Frontrunner XP CTO Catheter for, 633f Booster pump, 213 Borrelia burgdorferi, 335 Boston Scientific activity-sensing device, 148 Boston Scientific Acuity Bear-Away Inner Catheter, 591f-592f Boston Scientific dual-sensor pacemaker, 152-154, 153t Boston Scientific ICD Automatic Gain Control for, 65 Guidant Model 1831 as, 901f Boston Scientific LV lead, 598-600 Boston Scientific over-the-wire LV pacing lead, 598f Boston Scientific pacemaker, 34 autocapture threshold test from, 353f Boston Scientific Rhythm ID algorithm, 101f Boston Scientific ventilation-sensing device, 149 Bradycardia cardiac pacing and, 234 vasovagal syncope and, 364-365 implantable recorder, 365 loop recordings, 370 pacemaker memory, 365 tilt-table test, 365 Bradycardia pacing, 211-213 goal of, 836 problems with, 907-908, 908t stimulation threshold and, 15 Bradycardia pulse generator, 179 Bradycardia timing cycle, dual-chamber, 816-825 Brain natriuretic peptide (BNP), 157 heart failure status and, 167f Branching atrioventricular bundle, 324f British Pacing and Electrophysiology Group (BPEG), 813 pacemaker codes by, 195 Brugada syndrome, 332, 384-385 beta-adrenergic blocker in, 390 inappropriate shocks for AF in, 389f risk stratification for, 384-385 sinus tachycardia during exercise, 388f therapeutic recommendations for, 385 ICD therapy, 386t ventricular fibrillations in, 386f Buddy wire technique, 655-656 for straightening vein segment, 656f for LV lead placement, 657f Bulldog lead extender, 761 Bundle branch, action potential of, 9f Bundle branch aberrancy, 93, 93f Bundle branch block (BBB), 323 acute myocardial infarction and, 340t electrocardiogram of, 341f mortality and sudden death rate, 341 after AMI and high-grade AV block, 343 diagnosis/prognosis for, 331 electrophysiologic study for, 328 Burst antitachycardia pacing, 379-380

1056

Index

Byrd Femoral Workstation, 762f, 766f Byrd’s technique, for access to subclavian vein, 459-460, 460f

C Cameron Heald S-ICD detection algorithm, 430 Canadian Implantable Defibrillator Study (CIDS) AVID, CASH and, pooled analysis of, 263 for ICD therapy, 262-263 criteria, comparison groups and results, 262t population details/mortality results, 262t Canadian Trial of Physiologic Pacing (CTOPP), 242 clinical events in, 242t critical appraisal of, 242, 249 intolerance to VVI(R) in, 250f sinus node disease and pacing, 305 Cannon A wave, 864 Cannulation catheter, 538-541 Can-to-patch shocking vector, 430-431 Capacitance, 4 at electrode-tissue interface, relationship to polarization voltage, 21-22 membrane depolarization and, 22-23 polarization versus, 18-19 sine-wave voltage and, 17 Capacitive current flow, 21 Capacitive reactance, inductive reactance versus, 17 Capacitor, 4 as battery power source, 186-189 as charged, 20 components of, 186 defibrillation performance, effect on, 189-190 energy delivery for, 187 energy density, 187 energy storage for, 186 failure modes of, 189 dielectric oxide degradation, 189 short circuit, 189 future of, 189 in ICD, 187 construction of, 187-188 non-ideal behavior of, 188-189 deformation, 188 internal resistance, 188-189 leakage current, 188 schematic representation of, 186f Capacitor charging initiation of, 88f rapid VT/VF detection and, 89f Capacity plot, load voltage versus, 177f Capture automated, 34 cause of loss of, 873b changes in, pacing system malfunction and, 867 Capture hysteresis (Wedensky effect), 15 Capture latency, 949 effect on EGM timing to electrical activity, 951, 951f Capture management, 79 algorithm/graph for, 867f Capture threshold, factors increasing, 873, 873b Carbon dioxide, iodinated contrast versus, 621 Cardiac action potential, 7-8 events producing, 7 origination of, 203 phases of, 7

Cardiac action potential (Continued) automaticity and conduction system, 8 final repolarization, 8 initial repolarization, 8 rapid depolarization, 7-8 Cardiac Arrest Study Hamburg (CASH) AVID, CIDS and, pooled analysis of, 263 for ICD therapy, 263 criteria, comparison groups and results, 262t population details/mortality results, 262t Cardiac automaticity gene therapy approach to, 191-193 molecular therapy experiments to induce, 192t Cardiac catheterization laboratory for pacemaker implantation, 444 view of, 444f Cardiac channelopathy Brugada syndrome as, 384 catecholaminergic polymorphic ventricular tachycardia as, 385 considerations for, 385-386 ICD therapy for, 383-392, 386t complications from, 387-390 Long QT Syndrome as, 383-384 Short QT Syndrome as, 384 Cardiac compass report, 861f Cardiac contractility modulation (CCM), 296 Cardiac cycle, events of, 205f Cardiac depolarization. See Depolarization Cardiac desynchronization, atrial fibrillation causing, 972f Cardiac electrical stimulation, 3-39 concepts of, 3-5 effects of, 3 Cardiac excitation ion channel and, 6f occurrence/mechanism for, 11 types of, 12f virtual electrode causing, 11 Cardiac implantable electronic device (CIED) atrial fibrillation and, 858 benefits/burdens of, 1044-1045 cardioversion or defibrillation, 1021-1022, 1022b communicating about goals of care, 1044t complications from hemothorax from, 742-743 implantation-related, 741 intrathoracic introducer approaches as, 742f lead dislodgment as, 741-742 lead stress/fracture, 742f perforation, 743 pneumothorax from, 742 pocket hematoma, 743 vein thrombosis, 743 deactivation of, 1040 logistics of, 1046-1047 direct-current cardioversion and defibrillation and, 1021-1022 electromagnetic interference and, 1004-1027 CIEDs, effect on, 1014b follow-up for scheduled, 988t unscheduled, 988b indications for, 741 infection and bacteriology of, 744-746 erosion and, 745f erythema and fluctuance, 744f

Cardiac implantable electronic device (Continued) fat necrosis, 745f incidence of, 744-746 management of, 746 presentation of, 744 prevention of, 744 purulent discharge, 745f risk factors for, 744 lead and device performance for, 999-1001 magnetic resonance imaging and, 1016f monitoring of. See also Automatic remote monitoring; Home monitoring economic/regulatory considerations, 1001-1002 HM event notification, 991f in-person, 987 manufacturer resources for, 989t patient-activated remote, 988-989 purpose of, 987 remote, 987-999 pain and, 743-744 patient’s right to refuse, 1040-1046 rights/responsibilities of clinicians, 1042-1043 physician choice for, 741 physician-initiated discussion and, 1043t programmer and, communication between, 1010 psychological impact of, 1038 radiofrequency current effect on, 1023 timing cycles and, 813 types of, 987 withholding therapy, 1048 Cardiac index, changes to, 397f Cardiac mechanical cycle, 938, 940f Cardiac memory, 210 repolarization abnormalities and, 210-211 Cardiac output atrial pacing and, 209f Doppler echocardiography examination/ calculation of, 216 Cardiac pacemaker. See Pacemaker Cardiac pacing. See also Pacing charge conduction/transmembrane potential changes in, 17-18 electric current flow, opposition to, 4 gradient for, 11 physiology and hemodynamics of, 203-233 principle of, 9 sinus node dysfunction and, 393 for symptomatic bradycardia, 211 for syncope treatment, 234 Cardiac perforation. See Perforation Cardiac pump function asynchronous ventricular muscle contraction and, 210 electromechanical events and, 911-920 LBB block and, 209 reduced, cause of, 210 Cardiac resynchronization ICD blanking period in, 71f sensing in, 68 SVT-VT discrimination in, 95-96 Cardiac Resynchronization in Heart Failure (CARE-HF), 285-288 endpoints in, 282t Kaplan-Meier estimates in, 288f extension phase, 289f types, criteria, endpoints and results for, 281t



Cardiac resynchronization therapy (CRT), 33 in acute settings, 279-280 advent of, 443 benefits of, 134, 516 cardiac function improvement with, 280t, 927-943 clinical trials of, 279-299, 295t complications from non-pacing operation-related, 980-981 complications of arterial versus venous system, 585-587 pacing operation-related, 976-980 coronary sinus access for, 535-541 contrast use in, 535-537 coronary sinus and, 489-490 coronary sinus lead positions in, 789f coronary venoplasty techniques for buddy wire technique, 655-656 Doppler echo optimization on hemodynamics in, impact of, 293f echocardiography for assessing response to, 294-295 future populations for, 295-296 goal of, 221 hardware system for leads and electrodes, 920 pulse generator, 920-922 heart failure and devices for, 296-297 hemodynamic/long-term remodeling effects of, 221f implant table for, 623f indications for, 836-837 lead design for, 136 loss of, causes for LV capture loss, 974-976 native ventricular activation competition, 971-973 pacing operation-related, 968-971 prevention of pacing on T wave, 971 LV ejection fraction and, 434 LV lead implantation and, 134, 519, 520f responders versus non responders, 521f LV remodeling and, 434 maintaining continuous, strategies for, 968 mechanical dyssynchrony, measurement of, 422f mechanisms of, 915-920 pacemaker AVI during, 936-938 pacemaker syndrome and, 226-227 pacing in, 434 physiology of, 220-221 programming considerations for LV pacing output voltage, automatic adjustment of, 925-927 pacing modes, 922-923 pacing outputs, 925 programming goal of, 928 response to, 294t comparison of, 974f echocardiography for assessing, 294-295 predictors of, 294-295 reverse volumetric LV remodeling, maximizing probability of, 927-943 sequential ventricular timing in, 959-961 for structural cardiac disease, 421-423 synchrony, strategies to restore, 219-226 ventricular activation wavefront fusion after, 933f

Index

Cardiac resynchronization therapy (Continued) ventricular activation wavefront fusion during, 927-929, 931, 933f Cardiac resynchronization therapy (CRT) defibrillator, left ventricular lead in, 790f Cardiac resynchronization therapy (CRT) trial, 281-290 for evaluating device features/programming, 292-294 long-term in special populations, 291-292 procedural safety and LV performance in, 290-291, 290t types, criteria, endpoints and results for, 281t Cardiac Resynchronization Therapy in Patients with Heart Failure and Narrow QRS trial (RethinQ), 291 Cardiac sarcoidosis, 271 complete heart block and, 335-336 Cardiac stimulation. See also Stimulation threshold metabolic effects on, 32 pharmacologic effects on, 32 Cardiac tamponade echocardiography diagnosing, 807-808 lead extraction and, 752 transvenous approach and, 765 as postimplantation complication, 806-807 Cardiac tissue, artificial electrical stimulation of, 8-13 Cardiomyocyte electric field, response to, 9f membrane composition of, 5 phospholipid bimembrane of, 5f Cardiomyopathy Trial (CAT) for ICD therapy, 266 criteria, comparison groups and results, 264t population details/mortality results, 265t Cardiopulmonary exercise testing, DDDR vs DDD pacing modes, 236 Cardiovascular mortality, pacing and, 246f Cardioversion, 1021-1022, 1022b CARE trial, 621 Carotid sinus, 362-363 Carotid sinus hypersensitivity, carotid sinus syncope and, 363 Carotid sinus massage cardioinhibitory and vasodepressor response to, 363f carotid sinus hypersensitivity and, 363 complications from, 363-364 indications for, 362-363 physiological responses to, 363 Carotid sinus reflex, 361 Carotid sinus syncope. See also Carotid sinus massage carotid sinus hypersensitivity and, 363 clinical perspective for, 361 diagnosis of, 362-364 history of, 361 occurrence of, 361 pacing for, 362t benefits of, 362 contraindications, 364 patient selection for, 362 physiology, 361 studies for, 362t support for, 364

1057

Carotid sinus syncope (Continued) symptoms of, 361 treatment of, 361-362 CAST study, 238 Catecholaminergic polymorphic ventricular tachycardia (CPVT), 385 nonsustained polymorphic ventricular tachycardia in, 390f risk stratification for, 385 therapeutic recommendations for, 385 ICD therapy, 386t Catheter, intimal flap, effects of, 586f Cathodal shock, 376-377 Cathodal stimulation, 11-13 action potential initiation by, 12f anodal stimulation versus, 23 isochronal activation maps after, 47f threshold at coupling intervals, 23, 23f Cathode, 4 batteries and, 175, 176f definition of, 175 resistance of, 16 Cathode break computer simulation of, 12f occurrence of, 12 Cathode limitation battery, 183 Cathode make computer simulation of, 12f occurrence of, 11, 12f Cell, as balanced, 177 Cell membrane, 5 Cell therapy strategy, for biologic pacemaker, 193-194 Cellular action potential, 41-42 defibrillating shock field effect on, 48 Cellular phone, electromagnetic interference and, 1011-1012 Cephalic vein, 454, 457 lead introduction into, 457f Cephalic venous access, for transvenous pacemaker placement, 456-457 Certification phase, of sensing, 117 CHADS-2 score-enhanced thromboembolic risk assessment, 999 Charge burping theory, 375-376, 376f Charge conduction, 17-18 Charge movement, in wires and tissue, 18 Chemical energy, batteries and, 175 Chemotherapy, heart block and, 335 Chest radiography. See also Preprocedural chest radiography CRT, lack of response to, 772 of dual-chamber pacing system, 786f of hemothorax, 806f of pneumothorax, 806f Children antitachycardia pacing in with congenital heart disease, 417-421 electrode placement/selection, 421 in atrial flutter, electrogram of, 415f congenital CHB and pacemaker free, 395, 395f CRT therapy for structural cardiac disease in, 421-423 device systems in, 798f dextrocardia in, 801f dual-chamber pacing contraindications for, 399 features for, 401

1058

Index

Children (Continued) dual-coil intrathoracic defibrillator system in, 420f dual-coil single-lead transvenous defibrillator system in, 419, 421f epicardial patch in, 419, 420f exit block and, 35 heart rate and exercise, 400f-401f ICD use in, 417 follow-up procedures for, 420-421 implantation approaches, 418-419 patient selection for, 417-418 programming considerations for, 419-420 support groups for, 425 initial pacemaker implantation in, 394f LQTS and pacemaker implantation, 395 pacemaker implantation and ambulatory electrocardiographic monitoring, 414-415 clinic visit, 412-413 exercise testing, 413-414 follow-up methods for, 412-417 follow-up periods for, 416 indications for, 395-396 intracardiac electrogram, 413, 414f prophylactic medication, 423 psychosocial adjustment, 423-425 remote/transtelephonic monitoring, 415-416 selection of, 396-409 support groups for, 425 survival rate with, 396f pacemaker implantation in anesthesia for, 486 expertise for, 486 leads for, 486 pacemaker pocket in, 486 permanent cardiac pacemaker in, 393 QRS complex in, 419 Rate-responsive pacing features for, 400-401 right ventricular pacing effects on, 217 single-coil transvenous defibrillator system in, 419, 421f transvenous permanent pacemaker implantation approach in, 485-486 unipolar versus bipolar pacing in, 404-405 Chronaxie, 13-14, 13f Chronic AV block, permanent pacing in, 337 Chronic bifascicular block, permanent pacing in, 338t Chronic circadian threshold variation, 35 Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF), 162, 163f, 296 diagnostic parameters for, 171t Chronotropic incompetence, 144, 154-156 definition of, 236, 825-827 in dual-chamber pacing, 235-236 incidence of, 144 lower rate limits and, 223-224 prevalence of, 155f for rate-adaptive pacing, 827 sensors in patients with, 154f sinus node disease and rate-adaptive pacing, 320 Circulating nurse, for pacemaker implantation, 444 Classic Mobitz type II, 324-325 Clavicle displacement, 455-456 anterior, 455f posterior, 455f

Clavicle-first rib lead discontinuity, 895f CLEAR trial, 225-226 Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision (CONNECT), 992 Closed-loop sensor system, 144, 145f Closed-loop simulation sensor, 146 advantages and limitations of, 151 syncope recurrence with, 371f types of, 151 unipolar ventricular impedance and, 150-151 Clot formation, venoplasty failure and, 660, 660f Coagulation, 1019 Coaxial lead, 128, 128f Cognis/Teligen model, Automatic Gain Control for, 65 Colapinto needle, 635 Combined heart failure diagnostics, 171f PARTNERS and, 170-171 Combipolar sensing, 880 Common bundle, action potential of, 9f Common law, 1040 Communicating, 195 Compact node, 323 Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION), 284-285 clinical characteristics of, 285t for ICD therapy, 266 criteria, comparison groups, and results, 264t population details/mortality results, 265t Kaplan-Meier estimates in, 286f patient characteristics and hazard ratios in, 287f study design for, 284f types, criteria, endpoints, and results for, 281t COMPASS-HF, 162, 163f Compensatory hyperventilation, 169-170 Competitive atrial pacing, 833 after premature ventricular complex, 835 prevention of, 833 Competitive ventricular pacing, 841 biventricular pacing with RV-based timing and, 841f Complete AV block, 334 Complete heart block (CHB). See also Heart block as acute or chronic, 330 ambulatory electrocardiogram showing, 395f cardiac sarcoidosis and, 335-336 congenital, 394-395 diagnosis of, 326 escape rhythm in, 326 incidence of, 342f infectious diseases and, 335 Stokes-Adams attack and, 330 symptoms/prognosis for, 330 Composite-wire conductor design, 129-130, 129f Computed tomography biventricular pacing, as nonresponder to, 808f device implantation and, 808 for LV lead repositioning, 808f Concentration polarization, 177 Concomitant symptomatic heart block, sick sinus syndrome and, 334 Conducted atrial fibrillation response effect on BiV pacing delivery, 975f pacing rate changes and, 972, 974f Ventricular Sense Response, combined effects of, 979f

Conducted electromagnetic interference, 1004 Conduction abnormal, activation sequence during, 206 cardiac action potential and, 8 of heart impulse, 204f Conduction block anterior line interaction, schematic view of, 956f-957f fixed versus functional, 952-953 implications of, 954 LV activation fusion, heterogenous effects on, 957f negative effects of, 959f posterior line interaction, schematic view of, 956f spontaneous/pacing-induced, implications during BiV pacing, 958-959 Conduction loss, 16-17 Conductor for pacing leads, 129-130 design of, 129 fracture of, 129 Conductor fracture, 791, 791f-792f, 807 non-physiologic, rapid make-break potential in, 902f Conductor resistance, 16-17 Conduit, creation of, 751-752 Confirmation/reconfirmation, 83-85, 88f Congenital AV block, 331-332 Congenital complete heart block, 394-395 children pacemaker free and, 395, 395f Congenital heart disease in children ICD use, 417 dextrocardia and, 797 Fontan procedure for, 797 Senning/Mustard procedure for, 797 special considerations for, 794-797 persistent left superior vena cava, 794 tetralogy of Fallot and, 797 transatrial endocardial atrial pacing in, 487f Congestive heart failure (CHF). See also Heart failure heart block and, 212 pacing and, 314 signs of, 157 sinus node remodeling in, 301-304 Connective tissue disorder, AV conduction disease and, 336 Connector terminal pin, 134, 134f high-voltage and low-voltage elements of, 140f CONNECT trial, 891 Conscious sedation, protocols for, 452t Constant-current stimulation, 25-26 constant-voltage stimulation versus, 24-26, 25f logarithmic plots of, 25f Constant-voltage stimulation, 25-26 constant-current stimulation versus, 24-26, 25f logarithmic plots of, 25f Constitutional right, 1040 Consumed charge, of battery, 180 Contact mapping, 207f CONTAK CD Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) and, 283-284 study design for, 283f Continuous atrial pacing algorithm, 832



Contraction pattern abnormal during LBBB and ventricular pacing, 206-211 at LV lateral wall pacing, 209f Contrast-induced nephropathy comparison of ionic versus nonionic, 621 low-osmolar nonionic versus iso-osmolar nonionic, 621 contrast volume and, 621 definition of, 620 periprocedural hydration for fluids for, 620 parts of, 620-621 protocol for, 620-621 prevention of, 620-622 risk factors for, 620b Contrast injection, 532f approach to, 530 coronary sinus cannulation with, 541-585 coronary sinus os and anatomy surrounding, 541-547, 544f-545f, 547f locating with, 538-541 defining obstruction, 637, 637f high-grade stenosis, demonstration of, 534f indications and recommendations for, 529 by operator and assistant, 532f simplified system for, 530f into subclavian vein occlusion revealing opening, 627f revealing total occlusion, 627f after venoplasty with previous cardiac surgery, 685f-686f without previous cardiac surgery, 689f venous access for, 530-533 Contrast media half-strength versus full-strength, 548, 548f importance of, 620 iodinated, 529 kidneys and, 620 occlusive coronary sinus venogram with with full-strength contrast, 549f with half-strength contrast, 548f osmolality of, 621 types of, 621 use of, 620 volume of, 621 Contrast staining cause of, 588-589, 589f balloon-induced trauma, 588-589 delivery guide, 590f extravasation, 588 from trauma, 588, 588f vein perforation, 590f subclavian venoplasty and, 655f Contrast venography, 464, 464f axillary venous access and, 462 Conus arteriosus, 507 Conventional echocardiography, LV inflow analysis and, 944-947 Conventional versus Multisite Pacing for Bradyarrythmia Therapy (COMBAT) study, 295-296 Convulsive incoordination stage, of ventricular fibrillation, 40, 41f

Index

Cook locking stylet first-generation, 760-761, 760f second-generation, 761 third-generation, 761, 762f Cook Pacemaker, 760-761 Cook’s Needle’s Eye Snare, 761, 763f Coping methods, for children with pacemakers, 423 Coradial bipolar lead, 128 Coronary Artery Bypass Graft (CABG) Patch trial, 257 for ICD therapy, 269 criteria, comparison groups and results, 268t population details/mortality results, 269t Coronary balloon anchored to regain venous CS, and target vein, 696f anchoring pacing wire, 694f angioplasty wire, loading on, 696f characteristics of, 693 indications for, 650 LV lead placement using, 693-694 subclavian vein occlusion, predilation of, 651f for subclavian venoplasty, 647-650 types of, 650 Coronary sinus advancing sheath or guide into, 558-585 balloon venoplasty of, 664f-665f composite illustration with guide in, 546f-547f coronary venoplasty and, 656-660 dissection of, on LAO clarified on AP view, 552f in LAO projection, 509f lateral wall vein and, RAO view of, 550f lead extraction from, 769, 769f left atrium, draining into, 560f for pacing, 489-490 in RAO projection, 509f venoplasty of, 662-664 after lead dislodgment, 667f-670f Coronary sinus access catheter definition of, 516, 618 intimal flap, effects of, 586f peel-away sheath for kink in, 537f use of, 537f removal of, 572-579, 581f anatomical, 537f nonanatomical, 536f, 572-578 shape of, 533 braided guide (core), 542f CS cannulation difficulties and, 555 with proximal curve, 558f-559f sheath for, 536f torque control and, 542f types of, 541f telescoping cannulation assist for, 526f Touhy-Borst valve, wire inserted through, 547f-548f types of Medtronic Attain Command 6250 series, 593f St. Jude, 596f vein perforation by, 524f vein selector and guide deploying through, 568 loading into, 571f Coronary sinus aneurysm, 587f Coronary sinus balloon venography, 788f

1059

Coronary sinus cannulation anchored balloon effect on, 697f braided guide (core) for, 565f catheter above proximal curve, 541f counterclockwise torque, effects of, 561f above CS, 540f below CS, 540f device combination for, 543f difficulties in, 556f anatomic variants, 555 balloon catheter, 563f downward sigmoid CS, 564f finding CS os, 555 small target veins, 567f stenotic CS, 564f tortuous initial segment, 561f valve preventing, 563f eustachian ridge/thebesian valve and assisting, 539f inhibiting, 539f process with contrast injection, 541-585 techniques for, 572 vein selector and guide of proximal target vein, 575f in tortuous vein, 570f vein selector failure and, 569f Coronary sinus defibrillation lead, 793 Coronary sinus fibrosis, 770f Coronary sinus lead positions in CRT, 789f radiography of positioning of, 782 Coronary sinus lead delivery system, 591f Coronary sinus os anatomy surrounding, 538, 538f contrast injection defining, 541-547, 544f-545f, 547f locating with contrast injection, 538-541 location of, 555, 559f high versus low CS, 559f variability of on anteroposterior projection, 543f high-to-low, 543f Coronary sinus vein balanced/anterior lateral patterns of, 558f cannulation of, 557f identification of, 556f midlateral/posterolateral patterns of, 557f Coronary sinus venogram balloon, 693 traction on, for cannulation, 693f-694f Coronary vein rupture of, 688f stent to straighten, 683f-684f Coronary venoplasty before and after, 522f, 684f coronary sinus and, 656-660 elements of, 662b equipment for, 693b left ventricular lead implantation and, 662-681 techniques for, 655-656 Coronary venous system active-fixation lead in, 135-136, 136f anatomy of, 547-554 basic patterns of, 554 LV lead fixation in, 135 Cost-effectiveness, of ICD therapy, 258-259 Coulomb, 176 Coulomb’s law, 3 Counterpressure, 757

1060

Index

Countertraction, 756-757, 757f CPS Universal Slitter, 597f Creatinine level, 622 Crista supraventricularis, 507 Crista terminalis, 505-506 Critical point formation of, 40 types of, 48 Cross-chamber blanking period, 60, 66 Cross-stimulation definition and cause of, 883-884 ECG rhythm strip showing, 883f Crosstalk, 127-128, 817-818 AV block and, 877f ECG rhythm strip showing, 877f factors promoting, 877, 877b inhibition of, 876-879 prevention of, 877-878 safety output pulse for, 878 safety pacing and, 878f Crosstalk sensing, 817 Crosstalk sequelae, prevention of, 878-879 Cross-ventricular endless-loop tachycardia, 976 CRT. See Cardiac resynchronization therapy (CRT) Cruzan v. Director, Missouri Department of Health case, 1040 Cumulative radiation, effects of, 1024 Current, 17-18 Current amplitude, 13 Current collector, in batteries, 176, 176f Current density, depolarization and, 10 Current of injury, 58 active lead fixation and, 476 at implantation, 61f Curved electrode/generator, 428, 429f Cutdown technique for axillary venous access, 462 for electrode placement, 456-457, 456f Cutter and telescoping hub guide, 582f-583f Cutting-balloon venoplasty focused-force venoplasty versus, 661-662 for stenotic target vein, 663f Cylindrical aluminum electrolytic, construction of, 187

D Daily life, electromagnetic interference and, 1011-1013 Damped sinusoidal monophasic waveform, 42 Danish multicenter randomized trials, 245 Danish study, 237 DDD atrial blanking period, 819f DDD-LV pacing, acute hemodynamics of, 435f DDD mode upper rate response, with Wenckebach AV block, 824f DDD pacemaker diagrammatic representation of function of, 817f intracardiac marker channel and, 65f DDD pacing atrial pacing versus, 243 clinical events in, 244t dual-chamber devices in, 816 indications for, 234 monoplane ventriculography during, 229f timing interval for, 816f two-lead electrocardiogram showing, 825f with ventricular-based lower rate timing, 828f

DDD refractory period, 818f DDD safety pacing window, 818f DDI pacing mode timing cycle in, 835-836, 836f VDI mode versus, 836 DDIR pacing mode, mode switching to, 830f DDD(R) pacing mode, 34 blanking and refractory period for, 65f managed ventricular pacing and AVB during exercise, 351f criteria for switching, 351f mode switching to, 833-834 mode switching to DDIR, 830f MVP versus, 317f DDD(R)-to-AAIR mode switching, 834f DDDR vs DDD, 156 Debridement of ICD pocket, 731f after lead extraction, 754 Decision-making process ethical principles underlying, 1042-1043 rights/responsibilities of clinicians, 1042-1043 participant support in family, 1045 health care provider, 1045 palliative care specialist, 1045-1046 psychiatric consultant, 1045 Defibrillation batteries and capacitor effect on, 189-190 causing refibrillation, 49-53 charge conduction/transmembrane potential changes in, 17-18 CIED patient undergoing, 1021-1022, 1022b direct depolarization/hyperpolarization, 10 dual-chamber versus ventricular pacing with, 247-249 effects of, 18 efficacy of, 43-44 electric (power-on) reset, 1009-1010 electric current flow, opposition to, 4 electric potential gradients/currents for, 10-11 gradient for, 11 membrane depolarization in, 22-23 minimum potential gradient requirement for, 44 monophasic versus biphasic stimulation, 26 postshock activation after failure of, 52f postshock cycles after failed and successful shocks, 51f after failure of, 50f principles of, 40-55 sawtooth model and, 45-46 sensing function, loss of, 875-876 strength-duration curve for, 375f strength-duration relationship for, 374 success of, 40, 42-53, 375f Defibrillation lead header, evolvement of, 733 Defibrillation system echocardiography and, 807 identification of, 771 radiography of, 771 Defibrillation testing at ICD implantation electroporation, 377-378 energy testing, 377-378 indications for, 377 as programming guide, 378 risks of, 378-379

Defibrillation threshold, 42, 498f, 710f amiodarone increasing, 907f azygos vein defibrillation coil for, 498-499 drugs and clinical conditions affecting, 375t high, interventional approach to, 711, 711f increase in, factors contributing to, 904-905, 905t patient with high, 379 management of, 380f phase maps for shock, 44f potential gradient value and, 44 RV electrode polarity influence on, 376t subcutaneous coil placement for, 717f subcutaneous defibrillation electrode for, 497-498, 498f for subcutaneous ICDs, 430f Defibrillator. See also Implantable cardioverterdefibrillator (ICD) battery chemistries in, 182-183 cutaway view of, 183f electric circuits of, 4 increased standards for, 734 pediatric pacing and, 393-427 power systems for, 175-190 voltage-time curve during shock by, 183f Defibrillator adapter, 735t Defibrillator code, 196-197 Defibrillator lead design of, 128-129 in large posterior lateral vein, 552f radiography of, 771-794 Defibrillators in Acute Myocardial Infarction Trial (DINAMIT) for ICD therapy, 269-270 criteria, comparison groups and results, 268t population details/mortality results, 269t Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, 257 ICD shocks and, 258 for ICD therapy, 268 criteria, comparison groups, and results, 264t population details/mortality results, 265t Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) trial, 273-275, 275t Defibrillator therapy. See also Implantable cardioverter-defibrillator (ICD) therapy clinical trials of, 257-278 randomized controlled trials for, 261f Delayed afterdepolarization (DAD), 49 indications for CPVT, 385 Delayed AV coupling, 911 Delivered capacity lithium-iodine battery and, 181 resistance and voltage, relationship between, 180f Delivery catheter system, 437 Delivery guide angioplasty wire, loading on, 696f contrast staining from, 590f coronary sinus, advancing into, 517f CS access catheter and deploying through, 568 loading into, 571f definition of, 516, 523, 618 for lead placement, 525f advancing to target vein, 574f advantages and limitations of, 576f



Delivery guide (Continued) lumen size of, 568 Medtronic Attain over-the-wire 4194 pacing lead requirement for, 606f removal of, 572, 579f lead length and, 581f renal-shaped, with vein selector, 528f shape of, 523f new approach to, 526 previous approach to, 524-526 selection of, 568 supporting Quarter lead, 612f tip section, comparison of, 524-526, 526f-527f in tortuous vein, 570f types of comparison of, 597f Pressure Products, 595f St. Jude, 597f use of, 524-526, 524f Deltopectoral area, anatomy of, 502f Deltopectoral groove, 460 anatomy of, 456f needle and syringe trajectory, 462f subpectoral approach and, 502f superficial landmarks of, 461f view of incision perpendicular to, 461f Dental equipment, electromagnetic interference and, 1023-1024 Depolarization, 7-8. See also Direct depolarization; Rapid depolarization approaches to, 10 cardiac action potential and, 7 electrical stimulus and, 10 initiation of, 8 Ohm’s law and, 10 prevention of, 11 sensing of, 56 ventricular, recording of, 57-58 Detection, 56-126 of atrial tachycardia, 118f programming/troubleshooting for, 104-109 using subcutaneous electrocardiogram, 116-117 zones/zone boundaries for, 104-106 Detection algorithm, 56 Detection duration of ventricular fibrillation, 106-108 of ventricular tachycardia before ATP, 106 Device advisory notice. See Product advisory Device circuitry, EMI in, 1015 Device deactivation, 1040 clinical settings for, 1047 acute care hospital with electrophysiologic expertise, 1047 at home, 1047 inpatient facilities without electrophysiologic expertise, device deactivation and, 1047 consequences/uncertainties of, 1044-1045 end-of-life, preventing shock and ethical dilemmas in, 1043 ethical and legal principles of, 1040-1046 industry-employed allied professional, role of, 1047 logistics of, 1046-1047 overall goals of care and, 1043-1045 in pediatric patient, 1047-1048 rights/responsibilities of clinicians, 1042-1043

Index

Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE HF), 223, 292-293 Device implantation computed tomography and, 808 in D-transposition of great arteries after Mustard procedure, 802f fluoroscopy and venography of, 801-806 in infants and children, 798f interventional techniques for, 618-718 electrophysiologic versus, 618-619 special skill set, 619 morbidity and mortality rate, 619 preimplant preparation, 622b catheter manipulation/contrast injection, 622 room setup and table position, 622 preparation for, 622-625 Device malfunction communication after identification of, 1034 replacement rate for, 1028 Device performance definition of, 1029 factors affecting, 1028 surveillance of, 1031-1034 Device recall, 1033-1034 psychological impact of, 1038 Device registry for CIED performance, 1028-1029 National Cardiovascular Device Registry (NCDR), 1002 pacemaker and ICD malfunctions in, 1030f Device reliability definition of, 1029 role of, 1028 Device removed from service unrelated to malfunction, 1029 Device replacement elective or repair, 730-732 guidelines and techniques for, 730 surgical considerations for, 729-733 tools for, 737f venography and, 729 Device therapy, withholding, 1048 Dexamethasone-eluting reservoir, 133f Dextrocardia, 797 radiographic view of, 800f-801f DF-1 header standards, 197-198 DF-4 dual-coiled ICD header, 199f DF-4 dual-coiled ICD lead, 199f DF-4 header/lead technology, 197-198 DF-4 lead configuration, 735f Diagnostic radiation, electromagnetic interference and, 1021 Diaphragmatic myopotential, 77 oversensing of, 81f Diaphragmatic sensing, high-grade AV block and, 899f Diaphragmatic stimulation, 864 Diastolic dysfunction atrioventricular block and, 943-944 echocardiographic filling patterns of, 941f Diastolic function, 938 asynchronous activation effect on, 209-210 atrial pacing effect on, 953f electrocardiographic patterns of before/after preload reduction, 940-941 preload changes modifying, 940-941, 941f

1061

Diastolic function (Continued) increased contraction/relaxation times on, 941f loading conditions, effects of change in, 940f pacing rate change effect on, 942f pressure gradient and, 940f Diastolic interval (DI) action potential duration and, 41 fibrillation and, 41 Diathermy, 1018-1019 Dielectric, 4 Differential atrial sensing, 883 Differential atrioventricular interval (AVI), 818f, 820f Digoxin toxicity, 326 Dilated cardiomyopathy (DCM), 912 LBBB as cause of, 914 Dilator complications from, 648f directing glide wire, 628f exchanging, 626-627, 629f subclavian venoplasty versus, 646-655 “Dip” phenomenon, 23 Direct-current cardioversion and defibrillation, electromagnetic interference and, 1021-1022, 1022b Direct depolarization, defibrillation and, 10 Directed needle catheter, for total occlusion, 636f Direct electrical stimulation, 3 Direct His bundle pacing, 511 Direct needle puncture, 635 Direct traction, 755-756, 756f Discoordination, mechanical asynchrony versus, 222 Discrimination building blocks for, 85-88 of tachycardia atrial rate equal to ventricular rate, 96t atrial rate greater than ventricular rate, 97t Discriminator confirmation/redetection/episode termination by, 83-85 overriding, features for, 101-103 role of, 83-85 single-chamber versus dual chamber, 96 of tachycardia, 98f Disease-related biomedical factors, children with pacemakers and, 423 Distal conduction system, pharmacologic stress testing of, 328 Dog boning, 623 DOO pacing mode, 836 Doppler echocardiography, cardiac output examination/calculation with, 216 Doppler flow detection, for axillary venous access, 462-463, 463f Dotter snare, 761 Drain plot, load voltage versus, 177f Draping, for pacemaker implantation, 450-451, 451f Drawn brazed strand (DBS) method, of conductor design, 129f Drawn filled tube method, of conductor design, 129f Drift velocity, 18 Drug-induced bradycardia, 336 D-transposition of the great arteries, 797 device systems in, 802f pacemaker system in, 803f

1062

Index

Dual Chamber and Atrial Tachyarrhythmias and Adverse Events Study (DATAS) clinical events in, 248f purpose of, 248 Dual Chamber and VVI Implantable Defibrillator (DAVID) trial, 223-224 clinical endpoints in, 248t RVA pacing and, 350 RV pacing and, 725 with VVI backup pacing, 248 Dual-chamber building block atrial versus ventricular rate, 85 purpose/weaknesses of, 89t Dual-chamber DDD pacing, single-lead VDD pacing versus, 235 Dual-chamber discriminator, 96 Dual-chamber generator, longevity of, 397f Dual-chamber hysteresis, 835 Dual-chamber ICD atrial sensing in, 67 EMI and EAS in, 1006f sinus tachycardia during exercise with, 388f SVT-VT discrimination in, 95-96 Dual-chamber pacemaker crosstalk inhibition in, 876-879 DDD pacing and, 234 fusion avoidance algorithm for, 355 mode, rate, parameter change, cause of, 866, 866b noise reversion/electrical reset responses of, 1008t rate drop-responsive pacing with, 370 sensing system of, 56 Dual-chamber pacing mode advantages of, 234 atrial-single chamber pacing versus, clinical trials for, 243-247 chest radiograph of, 786f in children, features for, 401 in chronotropic incompetence, 235-236 contraindications for children, 399 cost-effectiveness of, 253 double-blind crossover studies for, 239-243 event markers for, 851 Medicare trial and, 239 pacemaker syndrome and atrioventricular dyssynchrony during, 228-229 postventricular atrial refractory period (PVARP) and, 401 randomized controlled trials for, 234 rate-adaptive ventricular pacing (VVIR) versus, 235t rate-modulated, laddergramming from, 853f rate response, with versus without, 236-237 runaway pacemaker in, 879 sick sinus syndrome, RCT for, 245 superiority of, 234 timing cycle in, 836 AOO, VOO, DOO modes, 836 DDI mode, 835-836, 836f VDD mode, 835, 836f VDI mode, 836 triggered versus inhibited mode, 235 upgrading to, 725 venous access for, 468b ventricular pacing versus, 238-243 in defibrillator patients, 247-249 ventricular pacing with rate response versus, 234-235

Dual-chamber pulse generator PVARP extension on PVE, 882f tracings for, 854f Dual-chamber rhythm classification, 96f Dual-chamber timing cycle, 816-825 Dual-chamber venous access, methods of, 468-469 Dual-coil intrathoracic defibrillator system, 419, 420f Dual-coil single-lead transvenous defibrillator system, 419, 421f Dual-sensor pacemaker justification for, 153f patient selection for, 154t principles guiding, 152 types of, 152-154, 153t DVI-committed mode (DVI-C), 878-879 Dynamic atrial overdrive (DAO) pacing algorithm, 310 Dynamic atrioventricular delay, 818 Dyspnea, acute decompensated heart failure and, 156-157 Dyssynchrony, occurrence of, 911

E Early afterdepolarization (EAD), 49 Early recurrence of atrial fibrillation (ERAF), 119f EasyTrak LV lead, 598-600 instability of, 602f phrenic pacing and, 601f target vein, before/after placement of, 601f types of, 600 Echocardiography CRT therapy, assessment of, 294-295 for native/lead vegetation diagnosis, 808, 808f for pacemaker and defibrillation systems, 807 for pericardial effusion and tamponade diagnosis, 807-808 Echocardiography Guided Cardiac Resynchronization Therapy (Echo-CRT), 291 Edema, venoplasty failure and, 660, 660f Education, for vasovagal syncope, 365 Effective pressure, of balloon, 625 Effective refractory period, 8 Efficacy of ICD in Patients with Non-Ischemic Systolic Heart Failure (DANISH) trial, 274-275, 275t ELA-Sorin dual-sensor pacemaker, 153t, 154 ELA-Sorin over-the-wire LV pacing lead, 600, 603f stylet-driven, 603f ELA-Sorin ventilation-sensing device, 149, 151 algorithm for, 155f tracings for, 151f Elective replacement indicator battery changes and, 846 in implantable pulse generators, 180 Elective replacement time (ERT), 846 Electric (power-on) reset, electromagnetic interference and, 1009-1010 contemporary ICDs, 1010t dual-chamber pacemakers set to DDDR, 1008t Electrical activation abnormal sequence of, 206 as asynchronous cardiac structure/function, 210 clinical consequences of, 217-218 reduced pump function, 210 in LBB block, 206 physiology of, 203-211

Electrical activation (Continued) of RV/LV during baseline LBBB and BIV pacing, 223f during sinus rhythm, 203-204 three-dimensional isochronic representation of, 204f Electrical charge movement, in wires and tissue, 18 Electrical defibrillation, ventricular fibrillation versus, 40 Electrical dyssynchrony (asynchrony), 134 Electrical energy, batteries and, 175 Electrical impedance, 177 Electrical insulator, 8 Electrical noise artifact, 901f Electrical remodeling, 158 Electrical resynchronization, 960f Electrical signal oversensing, 127-128 Electrical stimulus capture by, 10 depolarization and, 10 single-cell excitation by, 9-10 threshold for, 10 Electrical storm, 258 Electrical testing clinician, for pacemaker implantation, 444 Electric charge, 3 Electric circuit, of defibrillator, 4 Electric current, 3 opposition to flow of, 4 Electric field, 3, 1004 cardiomyocyte response to, 9f decrease in, 1011 stimulus threshold and, 10 strength/directionality of, 3 Electric field gradient depolarization and, 10 electric charge and, directed motion of, 17-18 Electric potential gradient/current membrane depolarization and, 22-23 for stimulation/defibrillation, 10-11 Electric power, electromagnetic interference and, 1013 Electrocardiogram (ECG) of acute myocardial infarction, 341f after aortic valve surgery and AF, 327f atrioventricular pacing and, 216f AV conduction, P-R interval prolongation, RBBB, 327f of bipolar pacing system, 868f DDD pacing and, 825f electrode placement for, 56 for Long QT Syndrome, 383 LV/RV capture and, 923-925 from sick sinus syndrome, 394f simultaneous, rhythm strip and event markers, 848f surface versus intracardiac, 56 Electrocardiogram (ECG) tracing endless-loop tachycardia on, 882f with event marker legend, 852f functional noncapture and, 871f latency showing on, 874f of pacemaker programmed to VVI demand rate of 50 bpm, 869f demand rate of 60 bpm, 869f pseudofusion beats in, 875f pseudo-ventricular tachycardia on, 879f



Electrocardiogram (ECG) tracing (Continued) from pulse generator beyond elective replacement interval, 872f rhythms on different systems, 865f safety pacing on, 878f ventricular pacing on, 864-865, 864f Electrocautery for battery change, 730 contraindications for, 480 electromagnetic interference and, 1019 for pacemaker implantation, 446 Electrocoagulation, 1019 Electroconvulsive therapy (ECT), 1018 Electrode atrial, placement of, 474-476, 489f in bipolar pacing, 23 collagenous capsule around, 26f corrosion of, 23 as curved, 428, 429f design of fixation mechanism, 31 location, 32 materials for, 31 spatial/size relationship between pairs of, 31 electrical characteristics of, 410-411 epicardial, placement of, 478 features affecting performance, 26-28 geometric surface area of, 26-27 for ICD implantation, 494f in ICD lead, 138-139 ideal versus non-ideal, 22 for implantable leadless pacing system, 437 implantation of, 456-457, 456f increasing size, effects of, 56-57 longevity of, 397f microporous surfaces of, 27f, 30 in pacing leads design of, 131, 131f-132f implantation reaction from, 132-133 placement of, 403f for atrial endocardial electrogram, 61f for electrocardiogram, 56 with pores, 27 collagen formation, 30 repositioning of, 487 shock parameters and, 43 for single-chamber ventricular pacing, 398-399 size versus sensing performance of, 27-28 steroid-eluting, 30-31 strength-duration curve for, 411f surface area of maximizing, 27 porous versus microporous, 30 ventricular, placement of, 470-474, 489f virtual description of, 11 importance of, 11 occurrence of, 11 Electrode-electrolyte interface, 16 circuit representation of, 19f processes of, 21-22 reactance and charge movement at, 17 Electrode-myocardium interface EMI causing damage to, 1010 mechanical instability at, 31 Electrode polarity, 4 Electrode polarization, 18f Electrodessication, 1019

Index

Electrode system for subcutaneous ICDs, 121f types of, 56 Electrode-tissue interface capacitance at, relationship to polarization voltage, 21-22 Helmholtz capacitance and, 16 impedance at, 16-17 micrograph of, 30f Electrofulguration, 1019 Electrogram (EGM), 56-60 amplitude and slew rate of, 58 AV resynchronization, analysis for, 950f clinical descriptors of, 60f elements of, 852 pacemakers storing, 854 peak-to-peak amplitude measurements of, 853-854 recording of, 57f sensing occurrence in, 62f sinus rhythm with PVC, 890f tracings with event markers, 852f ventricular fibrillation, variability during, 63f Electrogram telemetry, 852-854 limitations of, 854 qualitative versus quantitative, 854 Electrogram truncation, 90, 92f Electrolyte, 4 batteries and, 175-176, 176f Electrolytic capacitor, 189 Electromagnetic compatibility, 1004 Electromagnetic field, 1004 types in MRI, 1014-1015 Electromagnetic interface (EMI), 56 minimizing, 827 Electromagnetic interference (EMI) CIEDs and, 1004-1027 definition and risk factors for, 1004 diagnosis of, 1006 dual-chamber ICD shock caused by, 1009f electronic article surveillance and, 1006f electrosurgery and, 1020 electric (power-on) reset, 1009-1010 generation, 1018-1021 management of, 1020, 1020b factors influencing, 1011b frequency of, 1004 knowledge of, 1005-1006 testing protocols, 1006 in vitro testing, 1006 in vivo testing, 1006 pacemaker and ICD response to, 1006-1011 communication inhibition, 1010 determinants of, 1010-1011 electric (power-on) reset, 1009-1010 electrode-myocardium interface damage, 1010 mode switching, 1007-1008, 1007f noise reversion/asynchronous pacing/electrical reset responses of, 1010t noise reversion/electrical reset responses of, 1008t noise reversion mode, 1008-1009 pacing interference, 1006-1011 rapid/premature pacing, 1007-1008 reed switch closure, 1010 spurious tachyarrhythmia detection, 1008 sources of, 1004-1005, 1005b acoustic radiation, 1005

1063

Electromagnetic interference (Continued) conducted, 1004 in daily life, 1011-1013 ionizing radiation as, 1004-1005 medical equipment and, 1021-1024 radiated, 1004 in working environment, 1014 Electromagnetic interference, causes of, 871t Electromagnetic spectrum, 1005f Electromechanical order, 911 Electromechanics, LBBB effect on, 916f Electromotive, 3 Electron charge of, 3 flow of, 3 Electron drift current, 18 Electron flow, ion flow versus, 18 Electronic article surveillance, 1006f Electronic article surveillance device, 1012-1013 Electrophysiologic study (EPS), 331t of atrioventricular conduction system disturbances, 327-328 limitations of, 328-329 usefulness of, 328 Electrophysiology (EP) catheter extravasation of contrast from from trauma, 588, 588f Electrophysiology laboratory testing, investigational sensor during, 122f Electroporation, 44-45 risk of, 377-378 Electrosection, 1019 Electrosurgery, electromagnetic interference and electric (power-on) reset and, 1009-1010 generation of, 1018-1021 management of, 1020, 1020b Electrosurgical dissection sheath (EDS), 759-760, 759f EMPIRIC study, 380 Empty heart syndrome, 361 Encapsulation, in leads, 748f Endless-loop tachycardia (ELT), 829-830 cross-ventricular, 976 detection and termination of, 883, 883f ECG rhythm strip showing, 882f initiation of, 881f occurrence of, 880-883 overview of, 881b prevention of, 881-883 rate of, 881 Endocardial activation, total, 208f Endocardial approach, for ICD implantation, 495 pectoral pocket for, 500-501 Endocardial bipolar lead, 872f Endocardial CRT, 435f Endocardial electrode system bipolar electrodes for, 404f in congenital heart disease, 487f at corrective cardiac surgery, 487 implantation technique for, 409-410 after atrial switch operation, 412f axillary vein approach, 410 transcutaneous pacing, 409-410 venous angiography, 410 longevity of, 397f long-term pulse-width thresholds for, 404f pediatric pacing and, 402-404, 402f types of, 406-408

1064

Index

Endocardial electrode system (Continued) acute thresholds for, 408f distribution of use, 407f Endocardial electrogram, 58f Endocardial lead placement alternatives to, 487-490 during thoracotomy, 487f-488f Endocardial LV stimulation, leadless pacing and, 434 Endocardial pacemaker, implantation of, in child, 402f Endocardial pacing contraindications to, 404b in right ventricular apex, 498f Endocardial stimulation, current amplitude/voltage for, 13 Endocardial unipolar lead, 872f Endocytosis, 29f End-of-life improving communication about, 1046 preventing shock and ethical dilemmas in, 1043 End of service (EOS), 846 ENDOTAK transvenous endocardial pace and shock electrode, 495, 495f Energy, 13-14, 13f joule as, 176 storage of, 21 Energy density, 176-177 for capacitors, 187 Energy output, generator and, 399 Enoxaparin, bolus dosing of, 725 Environment stress cracking cause of, 130f polyurethane degradation and, 130 Epicardial active-fixation steroid-eluting lead, 135f Epicardial approach, to ICD implantation, 493-495, 493f Epicardial CRT, acute hemodynamics of, 435f Epicardial defibrillation patch, 419, 420f Epicardial electrode system implantation technique for, 409 left thoracotomy approach, 409 median sternotomy approach, 409 subxiphoid approach, 409 longevity of, 397f long-term pulse-width thresholds for, 404f pediatric pacing and, 402-404 changes in, 402f placement of, 478 approaches to, 478 indications for, 478 types of, 405-406, 405f as unipolar or bipolar, 56 Epicardial lead, 782 Epicardial LV lead placement. See Surgical epicardial LV lead placement Epicardial LV pacing lead, as unipolar or bipolar, 920 Epicardial permanent pacemaker implantation approach, 453 Epicardial RA/RV pacing lead, radiography of, 790f Epimyocardial electrode, 405-406 Epinephrine, 33 Episode termination, 83-85 Eroding device, 736-737 Erosion, 736, 745f cause of, 745f of leads through implant pocket, 745f

Erythema, 744f ESTEEM-CRT trial, 291 Ethical issues, in device deactivation, 1040-1046 European Society of Cardiology (ESC), pacing mode selection guidelines, 253-254 Event counter telemetry histogram for, 856f information provided by, 858 limitations of, 858 objective of, 854-858 types of subsystem performance counter, 856-858 time-based system performance counter, 858 total system performance counter, 855-856 Event detection phase, of sensing, 117 Event marker, 848f annotations for, formerly used, 850-851, 851f displays for, 850-851 for dual-chamber pacing, 851 limitations of, 851-852 single-chamber pacing with, 851 surface ECG and, 850f telemetry for, 849-852 Event marker legend, ECG and EGM tracings with, 852f Event notification. See Home monitoring Event record display, 859f Evoked response, 34 automatic sensing of, 79 postpacing polarization artifact and, 83f Evolution sheath, 760, 760f Excimer laser sheath, 758-761, 758f Excitable gap, 41-42 Excitation. See also Cardiac excitation types of, 12f Excitation-contraction (E-C) coupling, 204, 204f-205f Exercise Atrioventricular delay interval and, 215f DDDR vs DDD pacing modes, 236 dyssynchronous activation effect on, 209 heart contractility and, 150 identification of, 151 heart failure and, 144 heart rate and, 144 in children, 400f-401f hemodynamics of, 825-827 sinus tachycardia during, 388f Exercise-induced transient AV block, 336 Exercise testing acute intermittent loss of capture during, 418f ECG recording, 416f multiblock development and syncope, 417f pacemaker follow-up in children, 413-414 strength-duration curve for, 419f change with time, 419f using treadmill, 153f Exercise test report, 860f Exertion response programming, 147 Exit block, children experiencing, 35 Exocytosis, 29f Extended bipolar ventricular electrogram, 86f-87f Extension of refractoriness hypothesis, 48 External defibrillator, 42 External electromagnetic interference, 74-75 cause of electric drill, 76f electroconvulsive therapy, 76f

External jugular vein, 454 Extracardiac signal, 74-77 Extracardiac stimulation, 864 causes of, 864b Extracellular space, 45-46 Extracorporeal shock wave lithotripsy (ESWL) effects of, 1023 indications for, 1023 Extra support wire, 516 definition of, 618 Extrinsic deflection, 852

F Failure to capture, 868-869, 872-874 Fallback response, heart rate and, 832 Family, supporting in decision-making process, 1045 Faraday, Michael, 21 Faradic current flow, 21 Far-field QRS wave, 862f Far-field R wave (FFRW), 57-58 oversensing, 74 minimizing, 62 prevention of, 67-68 postventricular atrial blanking/rejection of, 67-68 rejection of by atrial sensing features, 71f by Medtronic ICD, 68 by pattern analysis, 70f Femoral vein, lead extraction through, 766-767 Fibrillation action potential and, 41 diastolic interval (DI) and, 41 heart, mechanical activity of, 40 stages of, 40, 41f Fibrosis coronary sinus, 770f from encapsulated lead, 749f lead extraction and, 748f-749f Finger photoplethysmography (FPPG), 947-948 optimizing AV resynchronization and, 949f Firmware, 1029 First-degree AV block, 329 First-generation locking stylet, 760-761, 760f First-generation multisite pacing pulse generator, 922 First Multicenter Automatic Defibrillator Implantation Trial (MADIT-I) for ICD therapy, 263 criteria, comparison groups and results, 262t population details/mortality results, 262t Fishhook electrode, 405 acute implantation voltage and current threshold for, 406f threshold for, 406, 406f-407f Five-position ICHD pacemaker code, 195, 196t, 813 pacing modes described by, 197t Fixation mechanism, 133 Fixed conduction block anterior zone interaction of, 958f cause of, 952-953, 954f characteristics of, 953 implications of, 954 Fixed-rate ventricular pacing, 234 Fixed-rate ventricular single-chamber pacing (VVI), rate-adaptive ventricular pacing versus, 234, 235t



Flow of electrons, 3 Fluctuance, 744f Fludrocortisone acetate, for vasovagal syncope, 366 Flunarizine, 49 Fluoroscopy device implantation and, 801-806 for pacing system malfunction, 867-868 Flux density, 1004 Focused-force venoplasty, 618 of collaterals between veins, 663f cutting-balloon venoplasty versus, 661-662 for elastic obstruction, 654f Kevlar balloon and, 652-653 to resolve focal obstruction, 653f Fontan procedure, 393, 398 for congenital heart disease, 797 Footprint number, 159, 160f Formule fondamentale, 13 Frank-Starling relation, 205 failing ventricle and, 940f FREEDOM trial, 225-226 Frontrunner XP CTO Catheter, 632, 633f Functional atrial undersensing, 968 Functional conduction block, 952-953 implications of, 954 line of correlation with regional mechanical delay, 956f during LBBB activation, 955f manipulation during BiV pacing, 955f LV pacing and, 954 physiologic basis of, 954 Functional mitral regurgitation, 921f reduction in, 918-920, 920f Functional noncapture, 870-871 cause of, 873, 884f ECG rhythm strip showing, 871f Functional oversensing, 870-871 Functional undersensing, 874-875 “Funny” current, 7

G Gadolinium contrast agent, 621 Galvanometer, 13 Gap junction, 8-9, 45-46 General endotracheal anesthesia, 754 Generator characteristics of, 399-400 as curved, 428, 429f features for, 399-401 selection of, 396 single-chamber versus dual chamber, 399f survival curve for, 396f Generator mode selection, 396-399 Gene therapy approach, to biologic pacemaker, 191-193 Global Utilization of Streptokinase and TissueType Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial, 342-343 Glucocorticoid pacing thresholds, effect on evolution of, 31 stimulation threshold, effect on, 33 Gooseneck snare to control distal end of wire antegrade approach, 699f retrograde approach, 698f into sheath/out of hub, 700f view of, 698f

Index

Gouy-Chapman model, 20 Gouy-Chapman-Stern model, 20 Gravitational field, 3 Great arterial switch procedure, 804f Guardian device, 170 recordings from, 170f Guidant Endotak ICD lead, pseudofracture of, 797f Guidant Model 1831 ICD, 901f Guide support-based delivery system, 516-617. See also Left ventricular lead implantation components of, 523-524 indications for, 522-523 limitations of, 516 use of, 516 Glide wire, dilator directing, 628f

H Harvey, William, 8 HCN4 protein, 303f Health care provider children with pacemakers and implications for, 423 provider-family interactions, 424 decision-making process, participant support in, 1045 Heart anatomy of, 506f spatial relationships and, 456, 456f axial section of, 510f left anterior oblique (LAO) of, 507, 508f right anterior oblique (RAO) of, 507, 508f sections of, 507 Heart block. See also Complete heart block; Surgically induced heart block cause of, 334 congestive heart failure and, 212 development of, 394 effects of, 211-212 radiation therapy/chemotherapy and, 335 ventricular rates at rest in, 212f ventricular septal defect (VSD) and, 394 Heart contractility, exercise and, 150-151 Heart failure. See also Acute decompensated heart failure (ADHF); Congestive heart failure; Impedance AEG, VEG, and aortic pressure tracing in, 217f brain natriuretic peptide and, 167f cardiac resynchronization therapy (CRT) and, 296-297 cause of, 279 contact/noncontact mapping in, 207f detection of, 159-160 event notification for, 999, 1000f-1001f exercise and, 144 heart rate versus, 223-224 history and frequency of, 172f ICD therapy clinical trials for, 264-270 criteria, comparison groups and results, 264t pooled analysis of, 268 population details/mortality results, 265t map of RV and LV activation, 220f MID-Heft Study data and, 166f minute ventilation predicting, 169-170 monitoring of accelerometer, 159f pathologic changes, 158 physiologic changes, 158 mortality from, 161f

1065

Heart failure (Continued) OptiVol and, 166-167 level changes in, 165f prevention of, clinical trials for Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADITCRT), 289-290 Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction (REVERSE), 289 QRS delay and, 279 right ventricular pressure and, 161-162 sensors for, 158-170 activity monitoring, 159 heart rate variability, 159-160 monitoring, 156-171 types of, 158t transseptal time, total endocardial activation time, total QRS duration in, 208f ventricular asynchrony and, factors contributing to, 914 ventricular pacing and, 315-316, 315f “physiologic” pacing modes versus, 239 Heart failure hospitalization incidence of, 279, 999 randomized controlled trials for, 245f survival versus death with AT/AF vs no AT/AF, 973f HeartNet, 1033 HeartPOD LA pressure monitoring device, 163 Heart rate age and, 156 change, cause of, 866b drug therapy and mortality rate with changes in, 224f exercise and, 144 in children, 400f-401f fallback response for, 832 heart failure versus, 223-224 hemodynamics of, 825-827 histogram for, 856f myocardial perfusion and, 207-208 physiologic effects of, 211-219 rate-drop response to, 832, 833f sensor-indicated histogram for, 857f smoothing algorithms for, 832, 832f Heart rate variability footprint number and, 160f heart failure and, 159-160 Heart Rhythm Society (HRS) ICD and CRT implantation guidelines by, 491-492 pacemaker codes by, 195 Task Force on Lead Performance Policies and Guidelines, 1031 Helmholtz capacitance, 4 concept of, 22 decay of, 19, 19f electrode-tissue interface and, 16 pacing configuration of, 19f Helmholtz capacitor, 4 Helmholtz double layer capacitance effect of, 20 structure of, 21f Hemodialysis, 622 Hemodynamic Guided Home Self-Therapy in Severe Heart Failure Patients trial, 163, 296

1066

Index

Hemodynamic monitoring invasive finger photoplethysmography, 947-948 for optimal AV resynchronization, 947, 947f noninvasive, 947-948 Hemodynamic sensor for ICD, 121 investigational ICD, stored EMG and pressure tracing from, 123f Hemofiltration, 622 Hemothorax chest radiograph of, 806f in CIED implantation, 742-743 as postimplantation complication, 806 Heparin, bolus dosing of, 725 High defibrillation threshold management of, 380f transvenous ICD system and, 793, 795f-796f High-energy defibrillation lead header, evolvement of, 733 High-grade AV block acute myocardial infarction and, 340f BBB after recovery, 343 definition of, 330 diaphragmatic sensing in, 899f rhythm strip of, 330f, 337f High-intensity headlamps, for pacemaker implantation, 446f High osmolar contrast agent, 621 High-power battery, safety concerns with, 184-185 High right ventricular septal, 218 High-voltage coil, for ICD lead, 138-139, 138f High-voltage lead pin configuration, 725f His bundle capture, criteria for, 511 His bundle electrogram (HBE), 343, 343f His bundle pacing indications for, 218 radiography of, 787f His-Purkinje system AV block in, 325 atropine, 326f intracardiac tracing for, 326f Holter recording, of atrial fibrillation, 117f Holt-Oram syndrome, 332-333 Homburg Biventricular Pacing Evaluation (HOBIPACE) study, right ventricular versus biventricular pacing, 252 Home monitoring, 989 data transmission for speed/time for, 991f early detection with, 993f event notification for, 991f arrhythmia, 999 for atrial fibrillation, 994f generator malfunction, 996f heart failure, 999 heart failure diagnostics, 1000f-1001f lead fracture, 995f lead function, 998f follow-ups for, 998 Hook vein selector, 573f, 576f Hospitalization. See also Heart failure hospitalization acute decompensated heart failure and, 167f for atrial fibrillation, 307f Hydration fluid protocol for, 620-621 types of

Hydration fluid (Continued) hypotonic saline, 620 isotonic saline, 620 sodium bicarbonate, 620 Hydrophilic wire/catheter and balloons, 517, 618 Hyperglycemia, 33 Hyperkalemia, stimulation threshold, effect on, 33 Hyperpolarization, 9f defibrillation and, 10 Hyperpolarization-activated cyclic nucleotide (HCN), 439 Hypertension, ventricular remodeling and, 211 Hypertrophic cardiomyopathy (HCM), 271 oversensing in, 898f-899f pacemaker implantation and, 396 R wave versus T wave, 897 Hypertrophic obstructive cardiomyopathy during AAI pacing, 229f pacing in, 229 Hypothyroidism, 33 Hypotonic saline, 620 Hysteresis rate, 815, 815f atrial periods and, 815-816 dual-chamber and search, 835

I ICD capsule, scar tissue debridement in, 731f ICD header DF-4 dual-coiled, 199f standard IS-1/DF-1 dual coiled, 199f ICD-induced proarrhythmia, 892b ICD lead adapters for, 734-735 body uniformity, 141f connector terminals for, 139-140 defibrillation threshold for, 728 development of, 136-142 DF-4 dual-coiled, 199f electrodes and high-voltage coils for, 138-139, 138f engineering and construction of, 127-143 evolution of, 136-137 evolvement of, 733 extraction of, 140-141, 140f failure of, 141-142 shock coil ingrowth, 141f signs and symptoms of, 142b failure rate of, 897 insulation for, 139 interchangeability of, 724, 724f upgrade to adapter, 724f pacing/sensing capabilities for, 727-728 perforation of, 743f performance of, 429f placement of, 793-794 on anteroseptal wall of RV outflow tract, 794f positioning in tetralogy of Fallot with persistent left superior vena cava, 804f pseudodiscontinuity of, 793-794 pseudofracture of, 793f recent developments in, 140-141 sensing design for, 137-138 special issues for, 722-723 standard IS-1/DF-1 dual coiled, 198f structure of, 137, 137f study results of, 1031f survival rate of, 428 ICD lead adapter, 736f

ICD lead connector, 743f ICD pocket, debridement of, 731f-732f ICD. See Implantable cardioverter-defibrillator (ICD) ICD shock, 258 ICHD (Inner-Society Commission for Heart Disease Resources) five-position pacemaker code by, 195 pacing modes described by, 197t three-position pacemaker code by, 195, 196t modification to, 195 pacing modes described by, 196t Iliac venous access, 482-483, 483f Iloprost, 622 Immediate Risk-Stratification Improves Survival Study (IRIS) for ICD therapy, 270 criteria, comparison groups, and results, 268t population details/mortality results, 269t Impedance battery consumption, optimizing for minimum, 22 definition of, 17, 846-847 in extracellular electrolyte, 22-23 insulation defect and, 16 intracardiac, 168-169 intrathoracic, 164-168 pacing, effects of, 25f after lead implantation, 29 Medtronic Model 5880A, 24f principle of, 146 unipolar ventricular impedance and, 168 value measure by all vectors, 168f Implantable cardiac rhythm management device batteries in average versus instantaneous current drain, 178 design requirements for, 178 power requirements for, 178 pulse amplitude on pacing current, effect of, 179 pulse width on pacing current, effect of, 179, 179f shape, size, and mass constraints, 178 size, energy density, and current drain, 178 Implantable cardioverter-defibrillator (ICD), 117, 428-433, 499-500. See also Defibrillator; Subcutaneous ICD advisories for, 1033-1034, 1034f antiarrhythmia drugs effect on, 906b atrial/ventricular signals in EGM, 892f-893f automatic optimization of, detection algorithm for, 77-79 automatic sensitivity adjustment of, 67f batteries used in, 183-184 lithium-layered silver vanadium oxide-carbon monofluoride, 184 lithium-manganese dioxide, 184 lithium-silver vanadium oxide (LiSVO), 183-184 blanking and refractory period for, 61 capacitors used in, 187 construction of, 187-188 in children, 417 follow-up procedures for, 420-421 implantation approaches, 418-419 patient selection for, 417-418 programming considerations for, 419-420



Implantable cardioverter-defibrillator (Continued) psychosocial adjustment, 424-425 support groups for, 425 complications from device defects, 387 implantation, 387 inappropriate shocks, 387, 389f infection, 387 major versus minor, 749b never used device, 387-389 reoperation, 725 strategies to avoid, 389-390, 390t design of, implications of, 190 detection algorithm for, 84f electromagnetic interference and communication inhibition, 1010 determinants of, 1010-1011 electric (power-on) reset, 1009-1010 electrode-myocardium interface damage, 1010 mode switching, 1007-1008, 1007f noise reversion mode, 1008-1009 pacing interference, 1006-1011 rapid/premature pacing, 1007-1008 reed switch closure, 1010 shock by, 1009f spurious tachyarrhythmia detection, 1008 electromotive force for, 3 endocardial electrogram configuration for, 58f equipment for, 730f evolvement of, 889 extraction complications for, 429t follow-up for interventions for, interval/unscheduled, 738 noncompliance of, 729f header configurations for, 734f hemodynamic sensors for, 121 history of, 443 identification of, 863 implantation of approaches to, 493-495, 493f complications from, 1037t considerations for, 493 cosmetic approach, 503, 504f equipment for, 492-493, 493b indications for, 999 leads and electrodes for, 494f location for, 492-493 parts of, 492 personnel for, 491-493, 491b submuscular pouch for, 501-503, 502f techniques for, 490-491 with unipolar pacemaker, 905f implanted loop memory event recorder capability in, 855-856 inactivation of, 111 intervention for acute problems, 737-738 interventions for, interval/unscheduled, 738 longevity of, 179-180 malfunction of, 1028 annual number, 1028, 1029f-1030f mechanisms of, 1028-1029 registries of, 1030t MRI and, 809 neurostimulators and, 1018 noise reversion/asynchronous pacing/electrical reset responses of, 1010t oversensing in, 722, 722f

Index

Implantable cardioverter-defibrillator (Continued) correction of, 897 pacing algorithms in, 841-842 pacing problems with, 907-908, 908t P and R wave, sensing of, 60f performance of, 1028-1034 permanent cardiac pacemaker and, 443-515 pocket creation for, 496-503 abdominal, 496, 496f subcutaneous versus submuscular, 496t postimplant testing arrhythmia detection, 377 defibrillation testing, 377-379 pacing thresholds, 377 of tachyarrhythmia therapy, 379-380 power systems for, 175-190 product advisories for, 1028 programming recommendations for, 380, 381t radiation oncology center protocols for, 1024 radiography of, 773f-775f rate detection zones for, 88f removal from service, classification of, 1031-1032, 1032f replacement of, 729-733 resynchronization devices as, 279 selective site pacing for, 503-512, 505f sense amplifier, diagram for, 64f sensitivity, automatic adjustment of, 64 subcutaneous defibrillation electrode in, 497-498, 498f for sudden death prevention, 328 truncated exponential biphasic waveforms and, 42 tunneling and, 496-497 VT/VF detection failure by, 906-907 withholding therapy, 1048 Implantable cardioverter-defibrillator (ICD) malfunction clinical history of, 889 electrocardiography recordings and, 889 lead problems causing, 891 physical examination for, 889 radiographic evidence of, 891-892 remote telemetry for determining, 891 telemetry for, 889-891 troubleshooting of, 889-910 principles of, 889-892 ventricular fibrillation, failure to detect, 900f Implantable cardioverter-defibrillator (ICD) pulse generator older models of, 733f performance of, 1028 radiography of, 771, 778f-779f replacement of, 719 indications for, 720-721, 720b, 723-725 invasive evaluation for, 727-729, 729f noninvasive evaluation for, 719-729 reoperation, factors to reduce need for, 720b risks of, 1036 special considerations for, 719 tools for, 735-736, 735b, 737f Implantable cardioverter-defibrillator (ICD) therapy. See also specific trial names for ACC/AHA recommendations for, 273t for cardiac channelopathies, 383-392, 386t complications from, 387-390 for cardiac sarcoidosis, 271

1067

Implantable cardioverter-defibrillator therapy (Continued) clinical trials of, 257-278 assessing mortality, 275t contraindications for, 274t cost-effectiveness of, 275 efficacy: randomized trials, review of, 261-273 evolution of, 257, 260-261 growth of use of, 258f guidelines for, 273 for heart failure or LV dysfunction clinical trials of, 264-270 criteria, comparison groups and results, 264t pooled analysis of clinical trials, 268 population details/mortality results, 265t for hypertrophic cardiomyopathy, 271 indications for, 274t limitations of cost-effectiveness of, 258-259 reliability, 258 shocks, 258 utilization, 259 nonrandomized studies of, 270-271 primary versus secondary prevention in, 259 problems with, 905 prophylactic catheter ablation reducing, 904 quality of life and, clinical trials for, 257 risk assessment for, 275 for spontaneous/inducible ventricular arrhythmias, 261-264 criteria, comparison groups and results, 262t pooled analysis of clinical trials, 263 population details/mortality results, 262t Implantable device imaging of, 771-810 timing cycles of, 813-843 Implantable hemodynamic monitor (IHM) system, 162f, 296 Implantable leadless pacing system development of, 437-439 infection risk in, 438 intracardiac electrode for, 438f pulse generator for, 438f sensed signal, transmission of, 439 ultrasound transmission/focusing in, 439f Implantable loop recorder (ILR), 116 atrial fibrillation detection algorithm by, 120f radiography of, 771 stored EGM recording by, 119f nonsustained tachycardia, 120f types of, 780f Implantable pulse generator (IPG), 127 elective replacement indicator in, 180 Implantable sensor characteristics of, 144-146 chronotropic incompetence, in patients with, 154f classification of, 144-146, 146t technical, 145-146 for heart failure monitoring, 156-171 performance of, 146t for rate adaptation/hemodynamic monitoring, 144-174 role of, 144 Implantable subcutaneous monitoring, 116 Implanted loop memory event recorder, 855-856 Implant table, for CRT, 623f

1068

Index

Implied total atrial refractory period, interventricular refractory period and, 970f Impress Azygous Left (JL-3.5) catheter, 712f Indirect traction, 756 Inducible ventricular arrhythmia ICD therapy clinical trials for, 261-264 criteria, comparison groups and results, 262t population details/mortality results, 262t Inductance, 4-5 sine-wave voltage and, 17 Induction technology, 439 Inductive reactance, 5 capacitive reactance versus, 17 Industry-employed allied professional, role of, 1047 Infants device systems in, 798f transvenous permanent pacemaker implantation approach in, 485-486 Infarction ventricular remodeling and, 211 Infection CIED implantation and bacteriology of, 744-746 erosion and, 745f erythema and fluctuance, 744f fat necrosis, 745f incidence of, 744-746 management of, 746 presentation of, 744 prevention of, 744 purulent discharge, 745f risk factors for, 744 lead extraction for, 747-749 pacemaker implantation and, 444 antibiotic prophylaxis/wound irrigation, 452-453 antimicrobial irrigation protocols, 453t Infectious disease, complete heart block (CHB) and, 335 Inferior vena cava, pacemaker and generator lead insertion through, 489, 489f Inflammation exit block and, 35 lead implantation and, 29 Informed consent, for lead extraction, 754 Informed refusal, 1040 Infraclavicular pocket, 483f Infraclavicular space, musculoskeletal anatomy of, 458f Inherited AV conduction system disease, 332-333 Inhibition of Unnecessary RV Pacing with AVSH in ICDs (INTRINSIC-RV), 272 Injury. See Current of injury Inner-Society Commission for Heart Disease Resources (ICHD) five-position pacemaker code by, 195 pacing modes described by, 197t three-position pacemaker code by, 195, 196t modification to, 195 pacing modes described by, 196t Inotropy Controlled Pacing in Vasovagal Syncope (INVASY), 371 Inpatient facilities without electrophysiologic expertise, device deactivation and, 1047 Inpatient pacemaker implantation, 448-449 In-person monitoring, for CIEDs, 987

Instrument table custom-built, 529-530, 531f positioning for LV lead implantation, 529-530, 531f Insulation in pacing leads, 130-131 defect in, 16 recent developments in, 130 Integrated bipolar electrode system, 56 Integrated sliceable hemostatic hub technology for CS access catheter removal, 581f example of, 582f Intensified follow-up indicator, 846 Interatrial conduction time (IACT), 348 QuickOpt for estimating, 966f SmartDelay and, 966 Interface, between ion drift current and electron drift current, 18 Inter/intraventricular resynchronization, cardiac function improvement with, 280t Internal jugular vein, 454-455 International Study on Syncope of Uncertain Etiology, 369 Interpenetrating domains, 18 InterVA, 918f Interventricular asynchrony, 221 Interventricular conduction delay, 917 Interventricular decoupling, 912 Interventricular dyssynchrony, 912 Interventricular interval timing cycle, 965f Interventricular refractory period, 968 role of, 970f Interventricular timing (VV timing) automatic adjustment of QuickOpt, 966-968 SmartDelay optimization, 963-968 considerations for, 952-968 semi-automatic adjustment of, 968 Interventricular timing delay, 837-838 Intra-atrial electrogram, 876f Intracardiac electrocardiogram (ICEGM), of intrinsic beats and PVC, 876f Intracardiac electrogram (IEGM), 56 as pacemaker follow-up in children, 413 in DDD mode, 414f with left atrial pacing, 414f from unipolar atrial lead, 869f Intracardiac electrogram determination, 413 Intracardiac impedance, 168-169 intrathoracic impedance versus, 169t Intracardiac marker channel, 65f Intracardiac pacemaker, implantation procedure for, 435f Intracardiac shunting, 403 Intracardiac signal, ventricular oversensing and, 69-74 Intracardiac ventricular electrogram, 146 Intracellular calcium “sinkhole”, 49, 52f Intracellular space, 45-46 Intradevice interaction, 111-112 VT detection failure by, 113f Intra-Hisian block, 323 Intramyocardial electrode, 405 Intraprocedural complication, 747 Intrathoracic impedance advantages and limitations of, 168 algorithm performance for validation data set, 166f

Intrathoracic impedance (Continued) intracardiac impedance versus, 169t measurement of, 164f for pulmonary fluid status clinical outcome studies for, 165-167 device description, 164 feasibility studies for, 165 monitoring of, 165f variation in, 169f Intrathoracic subclavian vein puncture, anatomic orientation of safety zone for, 459f IntraVA, 918f Intraventricular asynchrony, 221 Intraventricular conduction system, 203 Intraventricular delay interval, 226 Intrinsic atrioventricular interval (iAVI), 911 definition of, 964 Intrinsic beat, ICEGM and surface ECG of, 876f Intrinsic deflection recording of, 56-57 slew rate and, 56 Introducer set, 457, 457f Invasive hemodynamic monitoring finger photoplethysmography and, 947-948 for optimal AV resynchronization, 947 Investigational ICD, 123f Iodinated contrast media. See also Contrast injection; Contrast media carbon dioxide versus, 621 indications and recommendations for, 529 simplified system for, 530f types of, 621 Ion, movement of, 3 Ion channel cardiac excitability and, 6f electrical activity and, 41-42 types of, 6 Ion drift, 8 Ion drift current, 18 Ion flow, 8 electron flow versus, 18 processes of, 21 Ionic contrast agent, 621 Ionizing radiation, 1004-1005 IS-1 connector, 872f IS-1 technology, 197-198 IS-4 lead configuration, 735f Isoelectric window, 49 Iso-osmolar contrast agent, 621 Isoproterenol, 33 Isotonic saline, 620

J Jackson-Pratt drainage system, 447f Johns Hopkins Protocol, for MRI studies with CIEDs, 1015-1016, 1016f Joule (j), 176 J-tipped polytetrafluoroethylene guidewire, axillary venous access using, 462, 463f Jugular venous access, 482

K Kaplan-Meier estimates in Cardiac Resynchronization in Heart Failure (CARE-HF), 288f extension phase, 289f



Kaplan-Meier estimates (Continued) in Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION), 286f in Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), 290f Kearns-Sayre syndrome, 333 Kevlar balloon, focused-force venoplasty and, 652-653 Key dual-chamber building block, 89t Kidney, contrast material and, 620 Kinetic energy, 435 Kirchoff ’s voltage law, 3 Koch’s triangle landmarks, 507f

L Laddergramming, 851 from rate-modulated dual-chamber pacing system, 853f LA-LV transmitral pressure gradient, 938 Laser crossing client/patient characteristics for, 637t complications, prevention of, 638-639 procedural characteristics for, 637t of superior vena cava occlusion, 641f of total occlusions, 635-639 limitations of, 638 orthogonal view, 639-646, 639f Latency definition of, 874 ECG tracing showing, 874f Lateral cardiac vein pacing, ventricular activation during, 932f Lateral wall vein LAO projection of, 551f LV lead implantation on, 566f occlusion of, 588f RAO view of, 550f-551f with selective injection of contrast, 553f Lead. See also Insulation; Pacing lead abandoned, radiography of, 791f in bipolar pacing, 23 broken/insulation defect in, 16, 722f, 807 oversensing from, 75-77, 79f performance effect from, 128 in cardiac resynchronization therapy, 134 complications from, 749b, 803-806 detection of, 803-806 conductor fraction and insulation break in, 807 design of, 128f, 136 encapsulation of, 748f engineering and construction of, 127-143 epicardial active-fixation steroid-eluting, 135f extracted/dislodged, replacement of, 664 failure of documentation of, 721-722 ICDs and, 428 signs and symptoms of, 142b fixation mechanism for, 133f, 135-136 for ICD implantation, 494f improper positioning of, 864 interchangeability of, 724 Lead Integrity Alert and, 80f long-term, testing sensing/pacing capabilities of, 727-728

Index

Lead (Continued) malfunction of, 721-722 identification of, 793-794 monitoring of function of, 998f performance, 999-1001 MRI-compatible, 809f older models of, 733f passively fixed, 30-31 perforation of, 589 preexisting, crossing obstructed/occluded vein in, 625-646 protrusion of, 794f radiographic/fluoroscopic identification of, 726-727 radiography of, 771 removal of, 747 classification of, 1031-1032, 1032f replacement of, 664 securing of, 478-481 in situ, replacement of, 664 stimulation impedance, importance of, 866-867 stress and fracture of, 742f structural integrity of, 728-729 structure and polarity of, 127-129 upgrade to adapter, 724f venous access, sacrificing for, 629-632, 632f Lead anchoring sleeve, 134, 134f Lead anode, 4 Lead cathode, 4 Lead clinical success rate, 747 Lead code, 197 Lead connector, 733-734, 743f configurations for, 734t Lead connector pin, device for, 780f Lead discontinuity, clavicle-first rib, 895f Lead dislodgment, 133 in CIED implantation, 741-742 EGM of, 894f example of, 892f-893f left ventricular, incidence of, 979-980 macro-dislodgment of, 741-742 micro-dislodgment of, 741-742 occurrence of, 737-738 perforation and, 807f postimplantation chest radiography of, 807 radiographic evidence of, 891-892 reducing risk of, 525f Lead extraction anesthesia for, 754 approaches to, 761-763 surgical, 767-769 transvenous, 764-767 clinical considerations for informed consent, 754 patient information/preparation, 753-754 pocket management, 754-755 procedure room, 754 clinical outcome of, 748t complications/risks of, 1037 conduit creation and, 751-752 from coronary sinus, 769, 769f definition of, 747 fibrosis, canine model of, 748f fluoroscopy during, 803 goals and outcomes for, 747 inactive leads, 752 indications for, 747-752

1069

Lead extraction (Continued) bilateral occlusion, 751f infection, 747-749 noninfected systems, 749 risk to patient, 751 thrombosis or venous stenosis, 751-752, 752f instruments for, 757-758 electrosurgical dissection sheath (EDS), 759-760, 759f evolution sheath, 760, 760f excimer laser sheath, 758-761, 758f locking stylets, 760-761, 760f mechanical sheath, 757-758, 758f snares, 761 left-sided implantation and, 769f MRI-related indications, 752 replacement of, 664 risks and outcomes of, 752-753 SVC tears, 752, 752f tamponade, 752 techniques and devices for, 747-770 techniques for, 755-761 counterpressure, 757 countertraction, 756-757, 757f direct traction, 755-756, 756f indirect traction, 756 traction, 755 training and skills for, 755 view of, 751f Lead failure cause of, 130 insulation failure and, 77f multiple shocks and, 897 Twiddler’s syndrome and, 891-892 Lead fracture home monitoring event notification for, 995f inappropriate shocks and, 723f oversensing and, 79f radiographic evidence of, 891-892 radiograph of, 895f view of, 727f Lead-generator interface, structural integrity of, 728-729 Lead impedance, 846-847 increase in, cause of, 848 measurements for, 848 measurements for pacemaker, reporting, 848, 849f pacing current and, 179-180 bradycardia pulse generator, 179 ICD longevity, 179-180 role of, 76-77 telemetry for, 848 Lead Integrity Alert, 80f Leadless pacemaker, 439f Leadless pacing challenges in development for, 438b concepts for, 434-440 experimental setup for, 436f induction technology for, 439 Lead perforation, 891-892 chest radiograph of, 897f Lead pin configuration, 725f Lead placement for baseline LBBB activation, 936f body response to, 29 pacing impedance, effect on, 29 platform for

1070

Index

Lead placement (Continued) catheter shape, 533 lumen size, 533 removal, cutting versus peeling, 533-535 sites for, 135-136 stimulus threshold and, 26 threshold changes as function of time after, 28, 28f ventricular undersensing/oversensing, 377 Lead slack, 805f Lead status, 846-848 Lead tip stabilization, sensing and, 58 Learned helplessness, 424 Left anterior oblique (LAO), 507, 508f coronary sinus in, 509f view of, 512f Left anterolateral thoracotomy approach, for ICD implantation, 494, 494f Left atrial contraction, after mitral valve closure, 224f Left atrial pacing, intracardiac electrogram with, 414f Left atrial pressure, 163 changes in, 164f monitoring of, 163, 296 Left atrial pressure sensing device, 163f Left atrium, coronary sinus draining into, 560f Left bundle branch, 323 Left bundle branch block (LBBB), 134 abnormal activation sequence during, 206 abnormal contraction during, 206-211 cardiac pump function, impaired, 209 effects of, 217-218 cardiac structure/function and, 211 characterization/registration of, 929 contact/noncontact mapping in, 207f dilated cardiomyopathy, cause of, 914 effects of, 912 electrical activation in, 206 electrical activation times for RV/LV during, 223f electromechanics, effects on, 916f impulse conduction in, 206 local energetic efficiency, effect on, 207-209 map of RV and LV activation, 220f pressure-volume loops during, 917f prognosis for, 217 trifascicular block and, 326-327 ventricular activation characterization during, 928-929 Left bundle branch block (LBBB) activation, 928-929, 955f Left bundle branch block (LBBB)-induced asynchrony, 915f Left bundle branch block (LBBB) ventricular activation lead position for, 936f LV longitudinal strain map and, 934f Left subcostal approach, for ICD implantation, 494-495, 495f Left superior vena cava, patient with, 554f-555f Left thoracotomy approach for epicardial electrode implantation, 409 for ICD implantation, 494, 494f Left ventricle filling pressure, 163 Left ventricular activation, in heart failure and LBBB, 220f

Left ventricular activation fusion, conduction block and BiV pacing effect on, 957f Left ventricular activation time (LVAT), 929 calculation using surface ECG, 930f Left ventricular assist device (LVAD), electromagnetic interference and, 1021 Left ventricular breakthrough time, 206 Left ventricular capture electrocardiography for determining, 923-925 loss of, 927, 974f single-cycle, 927 Left ventricular capture management (LVCM) diagnostic reporting and, 926 limitations and complications of, 927 operating constraints for, 927 operating details for, 926-927, 926f performance of, 927 programming options for, 926 purpose/role of, 925-926 short-long-short sequences/pseudo-crosstalk during, 928f threshold determination for, 927 uncertain atrial capture and, 927 Left ventricular conduction block anterior line interaction, schematic view of, 956f-957f posterior line interaction, schematic view of, 956f Left ventricular conduction delay, by stimulation proximal to line of block, 958f Left ventricular dysfunction biventricular pacing and, 352-353 ICD therapy clinical trials for, 264-270 criteria, comparison groups and results, 264t, 268t pooled analysis of, 268 population details/mortality results, 265t, 269t in specific circumstances, 268 Left ventricular ejection fraction, 210-211 cardiac resynchronization therapy and, 434 Left ventricular endocardial activation, 913 Left ventricular epicardial activation, 913 Left ventricular epicardial lead, 135-136 benefits of, 134 fixation mechanism for, 135 Left ventricular free wall, contraction patterns in, 209f Left ventricular free wall pacing, external work values during, 209f Left ventricular lateral wall pacing, contraction patterns at, 209f Left ventricular lead. See also Over-the-wire LV pacing lead in CRT-D, 790f CT for repositioning of, 808f dislodgment by stylet, 585f with electrode and tool, 614f failure of, 600f misplacement of, 490 procedural safety and performance of, 290-291, 290t replacing unstable, 610f in target vein, 598f types of Biotronik, 598, 598f Boston Scientific, 598-600, 598f EasyTrak, 598-600 Medtronic, 600-608 as unipolar or bipolar, 920

Left ventricular lead delivery system evolution of, 591-610 types of, 591 Boston Scientific, 591f-592f Pressure Products, 595f Situs LDS-2, 593f Left ventricular lead dislodgment, 979-980 Left ventricular lead implantation. See also Guide support-based delivery system abnormal, radiographic view of, 784f-785f anchor balloons for, 681-695 approaches to, 517-519 complications of EP versus open-lumen catheter with contrast, 587 lead perforation, 589 radiation exposure, 589 contrast material use for, 620 with coronary balloon as anchor, 693-694 coronary venoplasty and, 662-681 CRT and, 519, 520f responders versus non responders, 521, 521f equipment for, 711b extraction and, 769f failed antegrade/difficult retrograde push-pull technique, 679f-681f fluoroscopy/chest radiography at fluoroscopic error, 519-521, 519f second implantation, 520f with interventional techniques catheter/lead movement, preventing restricted, 530-532 contrast, 529, 530f details and rationale for, 529-530 equipment and room setup for, 529, 531f platform for, 533-535 steps summary for, 526-541 on lateral wall, 566f location for, 519 mid-thoracotomy/thorascopic approaches to, 613f repositioning of, 522f slack for lead, 585 insufficient, 586f snare for, 695-699, 700b types of, 698f target vein absence/phrenic pacing present, 691f-692f transseptal approach to, 517-518, 700-701, 701f-702f Selectsite snare approach to, 703f-706f types of, 519f venoplasty and, 664, 666f after dislodgment, 667f-670f venous access sheaths for, 535f Left ventricular outflow analysis, 947 Left ventricular pacing effect on ventricular repolarization, 983f functional conduction block emergence during, 954 fusion beats during, 917-918 pressure-volume diagrams during, 210f pressure-volume loops during, 917f sites for, 222 site-specific effects on VT initiation/termination, 982f ventricular proarrhythmias during, 980-981 Left ventricular pacing fusion, 917-918



Left ventricular protection period (LVPP), 68, 971-973 Left ventricular pump function, 912f Left ventricular refractory period (LVRP), 68 Left ventricular refractory period (LVRP) extension, 841f Left ventricular remodeling cardiac resynchronization therapy and, 434 reverse volumetric, 917-918 Left ventricular scar volume, quantification of, 925, 930f Left ventricular wall, three-dimensional reconstruction of, 218f Lenègre’s disease, 333-334 Lev’s disease, 333-334 Life-sustaining therapy patient’s right to refuse, 1040 legal cases confirming, 1041t Light-emitting diode (LED), 122f Line of block, 206 Lithium-carbon monofluoride battery, 181-182 discharge curve of, 182f Lithium-cobalt oxide, 185-186 Lithium-hybrid cathode battery, 182 discharge curve of, 182f Lithium-iodine battery, 181 cell structure of, 181 charge available for, 3 cutaway view of, 181f delivered capacity, effects of current drain on, 181 discharge curve of, 181 Lithium-ion battery. See also Rechargeable lithium–ion battery diagram of, 185f discharge curve for, 186f Lithium-layered silver vanadium oxide-carbon monofluoride battery, 184 discharge curve for, 185f Lithium-manganese dioxide battery, 184 voltage and internal resistance with extent of discharge, 184f Lithium-silver vanadium oxide (LiSVO) battery, 183-184 area-normalized resistance of, 184f charge time-optimized, 183-184, 184f discharge characteristics, plot of, 183f discharge of, 182f Lithotripsy, electromagnetic interference and, 1023 Load voltage capacity plot versus, 177f drain plot versus, 177f Locking stylet, 760-761, 760f Longevity, 178-179 Long QT Syndrome, 383-384 antibradycardia therapy in, 386-387 pacemaker implantation and, 395 risk stratification for aborted cardiac arrest, 383-384 age and gender, 383 electrocardiogram, 383 EPS study and family history, 383 genotype, 383 symptoms of, 383 therapeutic recommendations for, 384 ICD therapy, 386t ventricular tachycardia and, 903f

Index

Long-term high-energy lead, testing DFT for, 728 Long-term lead, testing sensing/pacing capabilities of, 727-728 Los Angeles County-University of Southern California Medical Center (LAC-USCMC) Coronary Care Unit (CCU) acute myocardial infarction with AV block, 338 AV block progression, 339 with BBB, 339 without BBB, 339 Low atrial septum lead, 511f Lower rate behavior, 823-825 Lower rate limits (LRL), 223-224, 823-824 Low osmolar contrast agent, 621 Low-pass filter, 42 Low-voltage lead pin configuration, 725f L-transposition of the great arteries, 797 in pacemaker system after Senning and great arterial switch procedures, 804f Lung wetness monitoring system, 875 Lyme disease, 335

M Magnet-activated paced rate, change in, 719 Magnetic field, 1004 decrease in, 1011 Magnetic reed switch closure, electromagnetic interference and, 1010 Magnetic resonance imaging (MRI) contraindications for, 808-809 implantable cardioverter-defibrillator (ICD), 809 device implantation and, 808 electromagnetic interference and, 1014-1018 CIEDs, effect on, 1014b types of, 1014-1015 high pacing rates caused by, 880 lead/generator artifact in, 1017f pacemaker and lead compatible, 809f radiofrequency field and, 1015 Magnet rate, for pacemaker, 846f Magnet response, of pulse generator, 721b, 863 Magney approach, to subclavian venipuncture, 461f Main coronary sinus balloon venoplasty of, 664f-665f venoplasty of, 662-664 Malfunction. See also Implantable cardioverterdefibrillator (ICD) malfunction; Lead, malfunction of definition of, 1029 Managed ventricular pacing (MVP), 219, 316 during AAI pacing, 319f AAI/R+ versus DDD/R mode AVB during exercise, 351f criteria for switching, 351f algorithm for, 833-834 causing ventricular tachycardia, 352f DDD(R) mode versus, 317f example of, 398f rhythm strips of, 317f in sinus node dysfunction, 398 Manufacturer and User Facility Device Experience (MAUDE) database, 1033 Manufacturer’s representative, for pacemaker implantation, 444 Maximum tracking rate (MTR), 822-823 P-wave tracking and, 826f

1071

McLeod Crossover Study, 368 Mean atrial interval (MAI), 830 Measured data, 844-848 battery status, 844-846 Measured data telemetry, 847f Mechanical activation physiology of, 203-211 during sinus rhythm, 204-206 Mechanical asynchrony determination of, 221-222 discoordination versus, 222 Mechanical dyssynchrony measurement, before CRT therapy, 422f Mechanical sheath, 757-758, 758f Median sternotomy approach for epicardial electrode implantation, 409 for ICD implantation, 494, 494f Medical Product Safety Network (MedSun), 1033 Medicare Recovery Audit program, 448-449 Medicare trial, 239 Medtronic activity-sensing device, 147, 147f Medtronic Atrial Capture Management feature, 34 Medtronic Attain Ability 4196 lead, 608 venous anatomy suitable for, 608f-609f Medtronic Attain Command 6250 series CS access catheter, 593f Medtronic Attain hybrid guidewire, 594f instability of, 602f phrenic pacing and, 601f Medtronic Attain left-sided heart lead, 604f Medtronic Attain over-the-wire 4194 pacing lead, 604, 604f coil anode of, 605f delivery guide, requirement of, 606f pacing threshold for, 606f proximal lead alignment phrenic pacing and, 607f with venous anatomy and withdrawal, 607f Medtronic CareLink Programmer 2090, features of, 447t Medtronic Chronic IHM, 161 Medtronic delivery guide and slicing tools, 594f Medtronic dual-sensor pacemaker, 152, 153t Medtronic ICD, far-field R wave rejection by, 68 Medtronic lead, 600-608 Medtronic Lead Integrity Alert (LIA), 76-77, 80f Medtronic Model 10295A, 407f Medtronic Model 1356, 24f Medtronic Model 3830, 408 implantation technique for, 410 Medtronic Model 4951 acute implantation voltage and current threshold for, 406f threshold for, 406f Medtronic Model 4951M(P), 406f Medtronic Model 4951P, 407f Medtronic Model 4965 acute implantation voltage and current threshold for, 406f Kaplan-Meier survival curve for, 407f threshold for, 406f Medtronic Model 4968, 407f Medtronic Model 5069, 406f Medtronic Model 5880A external pulse generator, 24f Medtronic Model 6917, 406f Medtronic Model 6937A, 498 Medtronic Model 7000A, 24f

1072

Index

Medtronic pacemaker, event log and histogram for, 861f Medtronic PR logic algorithm, 103f Medtronic Protecta ICD, 103 Medtronic ventilation-sensing device, 149 Medtronic Ventricular Capture Management feature, 34 Membrane space constant, 45 Metabolic storage disorder, 333 Metal detector, electromagnetic interference and, 1013 Metal ion oxidation, polyurethane degradation and, 130 Microdissection failure of, 635f success of, 632 of total occlusions, 634f Frontrunner XP CTO Catheter for, 632, 633f Microporosity, 27 Microvolt T Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients (MASTER), 272 Middle cardiac vein pacing, ventricular activation during, 932f MID-Heft Study data, 166f Midlateral free wall, LV lead placement and, 519 Midwest Pediatric Pacemaker Registry (MPPR), 393 data collected for, 394t Millivolt amplitude, 853-854 Minimum potential gradient, 43-44 for defibrillation, 44 sawtooth model and, 46 Minute ventilation, 169-170 Minute ventilation sensing, 149-150 limitations of, 150 Minute ventilation-sensing device clinical experience of, 149-150 types of, 149 Mitochondrial disorder, 333 Mitral valve closure, left atrial contraction after, 224f Mitral valve surgery sigmoid coronary sinus after, 562f tortuous proximal coronary veins after, 566f M-mode endocardiography, 207 Moderator band, 507 Mode Selection in Sinus Node Dysfunction (MOST), 240-241 clinical events in, 241t critical appraisal of, 241, 249 intolerance to VVI(R) in, 250f pacemaker syndrome in, 241, 241f pacing mode, clinical events according to, 309f RVA pacing and, 350 sinus node disease and pacing, 305 Mode switching AAI(R) to DDD(R), 833-834 activation from DDDR to DDIR, 830f during atrial flutter, 830-831 algorithms for, 831, 831f atrial sensitivity and, 831f cause of, 866b far-field R wave, 970-971 effect on frequency, duration, and symptoms, 831f electromagnetic interference and, 1007-1008, 1007f

Mode switching (Continued) histogram for, 856f, 861f in pacemaker, 830 purpose of, 970-971 Modified Elencwajg-Cardinal femoral approach, to transseptal left ventricular lead placement, 707f-710f Monitoring. See specific devices Monitor-only zone, for ventricular tachycardia, 83 Monochamber LV activation, 939f Monochamber LV pacing QRS hieroglyphic signatures during, 937f as atypical, 939f ventricular activation during, 931, 931f Monochamber LV pacing threshold, 925f Monochamber RV activation, 939f Monochamber RV apical pacing, 924 Monochamber RV pacing QRS hieroglyphic signatures during, 937f as atypical, 939f Monochamber RV pacing threshold, ventricular activation sequences during, 925f Monophasic stimulation energy requirements for, 26 in rabbit/frog ventricles, 26, 26f Monophasic waveform, 42-45 definition of, 374 Mortality in acute myocardial infarction and BBB, 341 atrial/dual-chamber pacing versus ventricular single-chamber pacing, 238-239 in atrioventricular block, 342f from heart failure, 161f ICD therapy clinical trials assessing, 275t pacing mode and, studies on, 239t sinus node disease and, 305-306 in relation to pacing mode, 238t “Mother rotor” hypothesis, of ventricular fibrillation, 40-41 Movement of ions, 3 mRNA, in sinus node, 302f Multicenter Automatic Defibrillator Implantation Trial. See also First Multicenter Automatic Defibrillator Implantation Trial (MADIT-I); Second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), 272-273, 295t for heart failure prevention, 289-290 Kaplan-Meier estimates in, 290f Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD), 281t CONTAK CD and, 283-284 study design for, 283f types, criteria, endpoints, and results for, 281t Multicenter InSync Randomized Clinical Evaluation (MIRACLE), 281t, 283 study design for, 283f Multicenter Investigation of the Limitation of Infarct Size (MILIS), 340-341 Multicenter Unsustained Tachycardia Trial (MUSTT) for ICD therapy, 263-264 criteria, comparison groups and results, 262t population details/mortality results, 262t Multichannel ECG recording system, for pacemaker implantation, 445

Multilumen ICD lead, 128-129, 128f Multiple shocks cause of, 892-904, 892t atrial fibrillation and, 902, 903f drugs or ICD, 902-904 lead failure as, 897 P wave, T wave, and atrial flutter, over sensing of, 897 supraventricular arrhythmias, 902 management of, 892 Multipolar impedance, 168-169 Multisite Stimulation in Cardiomyopathy (MUSTIC), 282-288 crossover study for, 282f Multisite Stimulation in Cardiomyopathy-Atrial Fibrillation (MUSTIC-AC), 281t Multisite Stimulation in Cardiomyopathy-Sinus Rhythm (MUSTIC-SR), 281-282 types, criteria, endpoints, and results for, 281t Muscular stimulation, 1018 Mustard procedure for congenital heart disease, 797 device systems in DTGA after, 802f Myocardial infarction, 257 Myocardial perfusion, heart rate and, 207-208 Myocardial scar, 925 Myocardial stimulation cellular aspects of cell membrane characteristics, 5 phospholipid bimembrane, 5 resting transmembrane potential, 5-6 by pacemakers, clinical aspects of, 28-33 Myocardium balloon inflation in, 681, 690f excitation-contraction (E-C) coupling in, 204, 204f fibrillation of, 40 Myocardium-electrode interface, 31 Myopotential inhibition inappropriate inhibition caused by, 870f oversensing and, 869-870 Myopotential oversensing, 77, 897, 900f Myopotential sensing, 897, 900f Myopotential tracking cause of, 880 ECG rhythm strip showing, 880f

N N-acetylcysteine, 621-622 NASPE/BPEG defibrillator (NDB) code, 196, 198t short form for, 197, 198t NASPE/BPEG generic (NBG) pacemaker code, 195-196, 197t revision to, 196, 197t, 814t examples of, 198t short form for, 197 NASPE/BPEG pacemaker-lead (NBL) code, 197, 198t examples of, 198t National Cardiovascular Device Registry (NCDR), 1002, 1033 Native ventricular activation, 971-973 Neck, anatomic structures of, 453, 454f-455f Needle’s Eye Snare, 761, 763f Negative AV/PV hysteresis, 821f Negative charge, 3 NEPHRIC Study, 621 Nephrotoxic drug, 620



Net reactance, 5 Neurally mediated syncope syndrome definition/types of, 361 pacing in neurally mediated, 361-373 Neuromuscular disease, 335 Neuronal axon conduction, voltage-gated channel and, 6 Neurostimulator, electromagnetic interference and, 1018 New York Heart Association (NYHA) diagnostic class, 223 right ventricular versus biventricular pacing, 252 Nichall’s landmarks, for axillary venipuncture, 460f Nighttime heart rate, 159-160, 161f Node, 4 Noise response algorithm, 827 Noise response pacing, 876f Noise-reversion mode, electromagnetic interference and, 1008-1009 Nominal pressure, of balloon, 625 for subclavian/innominate venoplasty, 647 Noncapture, 873b Noncompetitive atrial pacing, 833 ventricular timing and, 834f Noncontact mapping, 207f Nonfaradic current flow, 21 Noninvasive hemodynamic monitoring, 947-948 Nonsustained polymorphic ventricular tachycardia (NSVT), 390f No-output condition, 868-869, 868b Normal rhythm, sensitivity, automatic adjustment of, 64 North American Society of Pacing and Electrophysiology (NASPE), Mode Code Committee of, 195, 813 AV block risks, pacemaker recommendations on, 328 North American Vasovagal Pacemaker Study (VPS-I), 367, 367f Nurse anesthetist, for pacemaker implantation, 444

O Occlusion. See Total occlusion Occlusive coronary sinus venography, 548-550 balloons for, 589 compliant versus noncompliant, 589f trauma from, 588-589 contrast staining in, 588-589, 589f balloon-induced trauma, 588-589 delivery guide, 590f extravasation of contrast, 588, 588f unmasking of trauma, 588 vein perforation, 590f with full-strength contrast, 549f with half-strength contrast, 548f lateral wall vein and, RAO view of, 550f potential risks from, 589 target vein identified on, 576f Ohmic, 4 Ohmic polarization, 17 Ohm’s law, 4 depolarization and, 10 One-dimensional cable model, 45-46 bidomain model and, 47-48 Open-circuit voltage, of battery, 177

Index

Open-heart surgery for lead extraction, 768-769 surgical epicardial LV pacing for, 611 venoplasty after, 671f Open-loop sensor system, 144, 145f Operating room, for pacemaker implantation, 445 benefits of, 445-446 pitfalls for, 445 Optical sensor, 146 OptiVol, 166-167 increased fluid index, cause of, 168t level changes in, 165f threshold for, 167 Osmolality, of nonionic contrast agents, 621 Outpatient pacemaker implantation, 448-449 analysis of, 448t protocol for, 448b Overdrive Atrial Septum Stimulation (OASIS), 832 Overinflated balloon, 625 Oversensing. See also T-wave oversensing in antitachycardia device, 722f confirmation of, 870-871 definition of, 68-69, 847 of diaphragmatic myopotentials, 81f electromagnetic interference and, 1007 of external electromagnetic interference, 74-75 in far-field R wave (FFRW), 74 minimizing, 62 prevention of, 67-68 in hypertrophic cardiomyopathy (HCM), 898f-899f in ICD correction of, 897 ventricular fibrillation, 900f in implantable cardiac rhythm management devices, 722, 722f lead/connector problems causing, 75-77 lead fracture causing, 79f lead insulation failure causing, 77f myopotential and, 77, 869-870 output pulse, lack of, 869 pacing system inhibition and, 870 of pectoral myopotentials, 90-93 P-wave, 74, 75f of P waves, T waves, and atrial flutter, 897 types of, 72f ventricular, 814 VVI ventricular, 814f Over-the-wire balloon, 623, 624f Over-the-wire LV pacing lead Biotronik, 598f Boston Scientific, 598f ELA-Sorin, 600, 603f stylet-driven, 603f Medtronic, 604f Oxidation definition of, 175 occurrence of, 4

P Paced atrial event, 818 Pacemaker. See also Pacemaker implantation advisories for, 1033-1034, 1034f automated capture features of, 34 automatic capture verification, 353-355 automatic drug delivery systems, 371 automatic mode switching in, 78, 830

1073

Pacemaker (Continued) automatic optimization of, detection algorithm for, 77-79 battery chemistries in lithium-carbon, 181-182 lithium-hybrid cathode, 182 lithium-iodine, 181, 181f blanking and refractory period for, 61 Boston Scientific, 34 in children ambulatory electrocardiographic monitoring, 414-415 clinic visit, 412-413 exercise testing, 413-414 follow-up methods for, 412-417 follow-up periods for, 416 indications for, 395-396 intracardiac electrogram, 414f prophylactic medication and, 423 psychosocial adjustment, 423-425 remote/transtelephonic monitoring, 415-416 selection of, 396-409 support groups for, 425 survival rate with, 396f complications requiring reoperation, 725 current flow in, factors opposing, 16-22 current sensor-driven, 147-152 of defibrillator, 4 diagnostics for, 112, 113f dual-chamber, 56 electromagnetic interference and communication inhibition, 1010 determinants of, 1010-1011 electric (power-on) reset, 1009-1010 electrode-myocardium interface damage, 1010 mode switching, 1007-1008, 1007f noise reversion mode, 1008-1009 pacing interference, 1007 rapid/premature pacing, 1007-1008 reed switch closure, 1010 spurious tachyarrhythmia detection, 1008 electromotive force for, 3 endocardial electrogram configuration for, 58f equipment for, 730f equivalent circuit for, 20f event log and histogram for, 861f evolvement of, 443, 844 extraction complications for, 429t goal of, 223 for hypertrophic cardiomyopathy, 396 identification of, 863 implanted loop memory event recorder capability in, 855-856 increased standards for, 734 interventions for, interval/unscheduled, 738 leadless pacemaker and, co-implant of, 439f magnet rate, battery voltage and impedance of, 846f malfunction of annual number, 1028, 1029f-1030f registries of, 1030t measured data in, 844-848 battery status, 844-846 MRI-compatible, 809f myocardial stimulation, clinical aspects of, 28-33 neurostimulators and, 1018 operational modes of, 813 P and R wave, sensing of, 60f

1074

Index

Pacemaker (Continued) parameters and measured data in, 845f performance of, 1028-1034 power systems for, 175-190 product advisories for, 1028 rate modulation in, 346 replacement of, 729-733 safety, adequate margin of, 34-35 sense amplifier, diagram for, 64f sensing threshold in, 62 Sorin Group, 34 St. Jude Medical, 34 SVT-VT detection and, 112-116 telemetry in, 844 troubleshooting and follow-up for, 844-888 ventricular capture verification schemes for, 79 ventricular pacing, minimizing, 156 voltage threshold, determining, 399-400 Pacemaker adapter, 735t Pacemaker atrioventricular interval atrial pacing interaction with, 949-952 changes in, effect on aortic VTI, 926 effects of, 938-943 excessively long, atrioventricular coupling from, 944f optimal, during atrial sensing/pacing, 953f Ritter method for, 944-945, 945f summary of, 946f short, atrial transport block from, 943f use during CRT, 936-938 Pacemaker battery depletion, 721b, 721f Pacemaker capture, automatic assessment of, 79 Pacemaker clinic visit, 412-413 Pacemaker code five-position ICHD code as, 195 NASPE/BPEG generic (NBG) code as, 195-196 three-position ICHD code as, 195 Pacemaker-ICD interaction, 111 Pacemaker implantation anatomic approaches for, 453-456 antibiotic prophylaxis/wound irrigation, 452-453 in children anesthesia for, 486 expertise for, 486 leads for, 486 pacemaker pocket in, 486 complications from, 749b, 1037t day of anesthesia, sedation, and pain relief, 452, 452t draping process, 450-451, 451f patient preparation, 450 site preparation, 450-451 equipment for, 445 electrocautery device, 446 high-intensity headlamps, 446f monitoring equipment, 445, 445b multichannel ECG recording system, 445 pacing system analyzer, 445 spare parts/service kits, 446, 447b surgical instruments, 445, 445b, 445f facility for, 444 infection risk and, 444 inpatient versus outpatient procedure, 448-449 intervention for acute problems, 737-738 leads, pockets, and closure in, 478-481 neck, upper extremities, thorax, anatomic structures of, 453 payment for, 448-449

Pacemaker implantation (Continued) personnel for, 444 anesthetist or nurse anesthetist, 444 circulating nurse, 444 electrical testing clinician, 444 manufacturer’s representative, 444 OR versus CCL personnel, 444 physician or surgeon, 443-444 scrub nurse/technician, 444 uniform for, 451 postoperative care for activity, 481 discharge, 481 documentation, 481 follow-up, 482 monitoring, 481 preoperative orders for, 449-450 preoperative patient assessment for, 449 preoperative planning for, 447-450 radiography alternatives in, 486-487 site for, 456 special considerations for iliac venous access, 482-483, 483f jugular venous access, 482 transaxillary retropectoral, 485f wound drainage and, 480 Pacemaker lead engineering and construction of, 127-143 fracture of, 727f lead dislodgment in, 133 malfunction of, identification of, 782-793 radiography of positioning of, 780-793 removal from service, classification of, 1031-1032, 1032f Pacemaker lead conductor fracture, radiography of, 791f Pacemaker lead impedance, measurements for, reporting, 848, 849f Pacemaker-mediated tachycardia (PMT), 820-822, 821f algorithms for, 829-830 cause of, 879-883, 976 endless-loop tachycardia and, 880-883 intervention using PVARP extension, 830f ventricular extrasystole, terminated/initiated by, 822f Pacemaker memory, 365 Pacemaker pocket alternative cosmetic locations for, 483-485 anterior axillary line, 485f inframammary placement of, 484f in children, 486 creation of, 479 Pacemaker pocket stimulation, 864 Pacemaker pulse generator battery depletion, documentation of, 719-720 general magnet responses of, 721b magnet placement response, 726 malfunction of, 1028 mechanisms of, 1028-1029 performance of, 1028 radiography of, 771 reattachment of, 728f replacement of, 719 indications for, 720b, 723-724 invasive evaluation for, 727-729 noninvasive evaluation for, 719-729 reoperation, factors to reduce need for, 720b

Pacemaker pulse generator (Continued) risks of, 1036 tools for, 735-736, 735b, 737f Pacemaker Selection in Elderly Study (PASE), 240 clinical events in, 240t critical appraisal of, 240, 249 intolerance to VVI(R) in, 250f Pacemaker syndrome, 226-229 during AAI or AAIR pacing, 227-228 AAIR pacemaker recording, 228f atrioventricular dyssynchrony and, 228-229 continuous rhythm strip for, 227f long AV delays causing, 318 in MOST study, 241, 241f pacemaker system upgrade for, 476-478 pacing and, 314 pathophysiology of, 227 reflex pathways in, 228f sinus node disease and, 234 symptoms of, 227t, 314t treatment of, 227 Pacemaker system in D-transposition of great arteries after Senning procedure, 803f echocardiography and, 807 in L-transposition of great arteries after Senning and great arterial switch procedures, 804f radiography of, 773f-774f in subpectoral position, 772f Pacemaker system upgrade, 476-478 lead compatibility and, 476-478 tunneling and, 477 Penrose drain and lead for, 477f techniques for, 477-478 venous access for, 476 using contralateral subclavian venin, 477f Pace/sense connector pin, 134f Pace/sense connector pin terminal, 134f Pacing. See also Cardiac pacing antitachycardia and bradycardia, 15 APD restitution relationship during, 41f atrial fibrillation and, RCT for, 244f, 246 for atrioventricular block selection of, 346-353 survival rate with, 239t in cardiac resynchronization therapy, 434, 922-923 cardiovascular mortality and, 246f in chronic AV block, 337 congestive heart failure (CHF) and, 314 coronary sinus for, 489-490 Danish study on, 237 DDD(R) mode, 34 future perspectives on, 254 guidelines for selection of, 253-254 in hypertrophic obstructive cardiomyopathy, 229 leadless concepts for, 434 experimental setup for, 436f long-term leads for, 727-728 membrane depolarization in, 22-23 monophasic versus biphasic stimulation, 26 mortality and, randomized trials of, 239t, 243f pacemaker syndrome and, 314 patient preference of, 236f



Pacing (Continued) physiologic/pharmacologic effects on, 32-33 in post-AMI period permanent, 345-346, 345t temporary, 344-345 problems with, 907-908, 908t quality of life and, 314 radiofrequency current effect on, 1023 radiofrequency field causing inhibition of, 1016-1017 randomized controlled trials on, 237 critical appraisal of, 249-250 issues to consider, 249-250 limitations of, 253 sensor-driven, 154-156 for sinus node disease, 300-322 indications for, 318t survival rate with, 238t sites for, 222-223, 801 alternate, 801-803 strength-duration curve in, 374 Pacing artifact, ECG displaying, 868-869 Pacing current lead impedance and, 179-180 bradycardia pulse generator, 179 ICD longevity, 179-180 pulse amplitude, effect of, 179 pulse width, effect of, 179, 179f Pacing electrode features affecting performance, 26-28 geometric surface area of, 26-27 placement of, 403f Pacing impedance effects of, 25f after lead implantation, 29 Medtronic Model 5880A, 24f Pacing-induced conduction block, implication on BiV pacing, 958-959 Pacing lead anchoring sleeves for, 134 conductor design for, 129-130 connector terminal pins for, 134 development of, 127 electrodes and, 131-133 fixation mechanism for, 133 insulation for, 130-131 as isodiametric and lumenless, 129, 129f radiography of, 771-794 replacing unstable, 608f screw-in versus screw-on, 614f sensed signal, transmission of, 439 structure and polarity of, 127-129 subclavian venous access without, 642f-643f total occlusion without, 644f-646f unipolar and bipolar, 614f Pacing lead adapter/sleeves, 735f Pacing rate changes in, cause of, 866b diastolic function and changes, 942f rheobase voltage and, 15f stimulation threshold, effect on, 15 Pacing system failure of, 868b follow-up for, 885 high impedance, effects of, 22 identification of, 771 monitoring of frequency of, 885

Index

Pacing system (Continued) remote, 885 transtelephonic, 885 radiography of, 771 Pacing system analyzer (PSA), 10 EGM amplitude, measuring of, 852-853 for pacemaker implantation, 446, 446f Pacing system code, 195, 814t revised, 813 Pacing system malfunction behavior mistaken as, 863 capture/sensing threshold changes and, 867 differential diagnosis of, 868-876 failure of output, 868-872 fluoroscopic evaluation for, 867-868 oversensing and, 870 patient evaluation for, 860-862, 860b history/physical examination, 862 invasive analysis, 862b noninvasive testing, 862, 862b physical examination and telemetry, 864-868 radiography for, 867 undersensing and, 875 Pacing Therapies in Congestive Heart Failure (PATH-CHF), 283 types, criteria, endpoints and results for, 281t Pacing Therapies in Congestive Heart Failure II (PATH-CHF II), 281t Pacing threshold, 15f drugs increasing, 874b glucocorticoids effect on, 31 at ICD implantation, 377 long-term/diurnal variations in, 35 for Medtronic Attain, 4193 versus 4194, 606f metabolic abnormalities and drugs effect on, 58 Pacing to Avoid Cardiac Enlargement (PACE) trial, 292, 295t, 315-316 Pain, in CIED implantation, 743-744 PainFREE Rx study, 380 Pain relief, for pacemaker implantation, 452 Paired Transvenous Defibrillation trial, 430 Palliative care specialist, supporting in decisionmaking process, 1045-1046 Palliative surgery, for congenital heart disease, 797 Parallel circuit, 4 Paranodal area, HCN4 protein in, 303f Paroxysmal atrial fibrillation: DDD(R) with mode switching, 235-236 Paroxysmal AV block, 330-331 Paroxysmal high-grade AV block, 337f Parsonnet pouch, 501, 738f PARTNERS. See Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in patients with Heart Failure (PARTNERS-HF) Passive-fixation electrode, acute thresholds for, 408f Passive-fixation lead, dexamethasone-eluting reservoir in, 133f Passive-fixation tine, 133f development of, 127 dislodgment of, 133 Passive tines, sensing and, 58 Patient-activated remote monitoring, 988-989, 990f Patient advisory model (PAM), 163 Patient preparation, for pacemaker implantation, 450

1075

Peak endocardial acceleration (PEA), 146, 170 advantages and limitations of, 152 atrioventricular delay interval and, 225-226 clinical results of, 152 sensor and algorithm for, 151-152 types of devices for, 152 Pectoralis minor muscle, 459f Pectoral myopotentials, 90-93 Pectoral pocket, 500-501 for ICD implantation, 504f Pectoral sheath extraction, 629 Pediatric pacemaker implantation anesthesia for, 486 expertise for, 486 leads for, 486 Pediatric pacing defibrillator use and, 393-427 electrode placement for endocardial versus epicardial system, 402-404, 402f electrode selection for, 402-409 generator features for, 399-401, 402b characteristics of, 399-400 dual-chamber pacing, 401 rate-responsive pacing, 400-401 Pediatric patient, device deactivation in, 1047-1048 Pediatric transvenous ICD system, after Senning procedure, 803f Peel-away sheath kink in, 537f removal of, 584f use of, 537f Peeling, 533-535 Penetrating bundle, 323, 324f Penrose drain and lead, 477f Percentage biventricular pacing, 160-161 Percutaneous approach, for venous access, 457, 463f Percutaneous coronary venoplasty (PCV), 656 Percutaneous subclavian venipuncture, 460, 461f air embolization risk with, 466 prevention of, 467b complications of, 469-470, 469b introducer sheath buckling, 466f method for, 465, 465f figure-eight stitch, 466f Percutaneous transhepatic cannulation, 489-490 Perforation in CIED implantation, 743 echocardiography diagnosing, 808 of ICD lead, 743f of lead, 589, 891-892 chest radiograph of, 897f lead dislodgment and, 807f as postimplantation complication, 806-807 Pericardial effusion echocardiography diagnosing, 807-808 as postimplantation complication, 806-807 Pericardium cardiac tamponade and, 765 wall integrity, loss of, 765 Peripheral nerve stimulator, 1018 Peripheral subclavian vein occlusion, dilation of, 534f Peripheral venogram, for subclavian vein occlusion, 625-646, 626f, 781f

1076

Index

Permanent cardiac pacemaker in children, 393 implantable cardioverter-defibrillator (ICD) and, 443-515 implantation of, 489 indications for sinus node dysfunction, 393 surgically induced heart block, 394 Persistent left superior vena cava (SVC), 488, 488f, 794 absence of, 489 with absence of right superior vena cava, 488f atrial/ventricular electrode placement through, 489f ICD lead positioning in tetralogy of Fallot with, 804f radiographic view of, 799f types of, schematic representation of, 799f Personal media player, electromagnetic interference and, 1011-1012 Phantom reprogramming, 866 Pharmacologic stress testing, 328 Phase, 47-48 Phase angle, 17 Phase singularity, 47-48 shock-induced, creation of, 48f Phospholipid bimembrane, 5 of cardiomyocyte, 5f Phrenic nerve stimulation, 976 Phrenic pacing EasyTrak LV lead and, 601f LV lead placement absent of target vein and, 691f-692f Medtronic Attain hybrid guidewire and, 601f Medtronic Attain over-the-wire 4194 pacing lead and, 607f venoplasty and, 671, 674f push-pull technique, 675f Physical counterpressure maneuver, for vasovagal syncope, 365-366 Physician for ICD and CRT implantation, requirements for, 491-492 for pacemaker implantation, 443-444 Physiologic pacing mode atrioventricular block and, 238 heart failure and, 239 sinus node disease and, 319f Piezoelectric crystal, 146 use of, 158-159 Pinacidil, 49 Plasmablade, 480 Plateau phase, of cardiac action potential, 7-8 Pneumothorax chest radiograph of, 806f in CIED implantation, 742 as postimplantation complication, 806 from subclavian venipuncture, 470 Pocket erosion, 745f Pocket hematoma, 737 in CIED implantation, 743 Pocket infection, 744 Pocket management, after lead extraction, 754-755 Pocket twitch, 725, 737 Polarity, 3 Polarization, 4 of battery, 177 capacitance versus, 18-19

Polarization (Continued) definition of, 20 distorting effects of, 28 electrode, effect of, 18f Polarization overvoltage, 17, 18f Polyester (Dacron) Parsonnet pouch, 447f Polymorphic ventricular tachycardia. See also Catecholaminergic polymorphic ventricular tachycardia during BiV pacing, 983f Polytetrafluoroethylene (PTFE), 130 Polyurethane characteristics/types of, 130 degradation of, 130 Pore structure, on electrodes, 27 Positive atrioventricular interval hysteresis, 820f Positive charge, 3 Post-AV nodal ablation evaluation (PAVE), 252, 291-292 Postimplantation radiography, 806-807 complications from, 806-807 Post-market surveillance goal of, 1031 methods of, 1031-1032, 1031t Postpacing polarization artifact, 83f Postshock activation, 44, 49 during failed shock, 52f Postshock cycles, 50f-51f recordings/activation time for, 53f Postshock sensing, 67 Postventricular atrial blanking (PVAB), 60 atrial sensing, effects on, 69f of far-field R wave, 67-68 Postventricular atrial refractory period (PVARP), 60, 820-822, 821f dual-chamber pacing and, 401 endless-loop tachycardia and, 881-882 PVE and, 882f P-wave tracking caused by, lack of, 822f VDD system, pacemaker programming on, 348 Potassium channel gene, 332 Potential difference, 3 Potential gradient, 43-44 Power density, 1004 Power frequency, 1004 P-R dissociation building block, 85-88 Prediction of ICD Therapies Study (PREDICTS), 274 Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT), 295t Premature ventricular complex (PVC) after competitive atrial pacing, 835 EGM displaying, 890f extension of PVARP in response to, 822 ICEGM and surface ECG of, 876f ventricular electrogram during, 58 PREPARE study, 380 Preprocedural chest radiography, 771 dextrocardia and, 797 overlay of diagram on, 772f pacing/defibrillation system, identification of, 771 patient anatomy, identification of, 771 Pressure Products CS access catheter, 595f Pressure Products delivery guide, 595f Pressure sensor left atrial sensor as, 163 right ventricular, 161-162

Pressure-volume loops, during LBBB and LV pacing, 917f PREVENT-HF trial, 252 Procedural success rate, 747 Product advisory annual number of, 1034f clinical management of, 1038, 1038b balancing risks versus benefits, 1036 options for, 1036-1038 overview and clinician responsibilities, 1035-1036 device recalls and, 1033-1034 number, rate, and reasons for, 1033-1034 for pacemaker and ICDs, 1028 psychological impact of, 1038 threshold for activation of, 1033 Product notification, 1033 Programmed sensitivity, 62 Programmer CIED and, communication between, 1010 for implantable leadless pacing system, 437 pacemaker/ICD identification by, 863 Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in patients with Heart Failure (PARTNERS-HF), 170-171 diagnostic parameters for, 171t Progressively large dilator drawbacks of, 647 hemodynamic collapse in using, 648f subclavian venoplasty versus, 646-655 Propagation depolarization and, 10 electrical pacing stimulus and, 10 Prophylactic medication, for children with pacemakers, 423 Proton, 3 Proximal/distal subtotal venous occlusion, dilation of, 535f P-R patterns/relationship building block, 85-88 Pseudo-atrial undersensing Atrial Tracking Recovery and, 970 loss of CRT from, 968, 969f Pseudo-crosstalk, during LVCM, 928f Pseudodiscontinuity, of ICD lead, 793-794 Pseudofracture of Guidant Endotak ICD lead, 797f of ICD lead, 793f types of, 791 Pseudofusion beat, ECG tracing showing, 875f Pseudonormalization, 940-941 Pseudo-pacemaker syndrome, 911 Pseudo-ventricular tachycardia, 879 ECG rhythm strip showing, 879f Psychiatric consultant, supporting in decisionmaking process, 1045 Psychosocial adjustment, for children with pacemakers, 423-425 Pullback, 138f Pulmonary arterial pressure sensor, 163-164 Pulmonary artery pressure, 161 Pulmonary capillary wedge pressure, atrioventricular pacing and, 216f Pulmonary fluid status. See Intrathoracic impedance Pulmonic valve, 507



Pulse amplitude, 14f in generator, 399 pacing current and, 179 pacing threshold and, 15f programming of, 14f Pulse artifact present, 872-874 Pulse duration, 13, 14f programming of, 14f Pulse duration threshold, 13 Pulse generator, 16 for biventricular pacing, 923f for cardiac resynchronization therapy, 920-922 component failure of, 871-872 elective replacement indicator in, 180 failure of, 872b first-generation multisite pacing, 922 identification of, 726b make and model of, 726-727 radiographic/fluoroscopic, 726, 726f for implantable leadless pacing system, 437 inframammary placement of, 484f lead adaptability for, 733-737 location of, 771 longevity of, battery and, 178-179 magnet response of, 721b, 863 malfunction of, 1028 mechanisms of, 1028-1029 manufacturer and type of, 771 migration of, 771 radiography of, 771, 776f-777f with radiopaque identification tags, 863f replacement of approaches to, 719-740 indications for, 720b, 723-725 invasive evaluation for, 727-729, 729f noninvasive evaluation for, 719-727 procedure for, 730, 731f reoperation, factors to reduce need for, 720b risks of, 1036-1037 tools for, 735-736, 735b, 737f second-generation multisite pacing, 922 skin erosion from, 736 with vascular overload and abandoned lead, 727f ventricular IEGM telemetered by, 870f Pulse generator connector block, 733 Pulse generator-lead interface malfunction, 723 Pulse width, 13 battery longevity, programming for, 35, 35f in generator, 399 pacing current and, 179, 179f shock waveform and, 375f importance of, 375 Pure capacitance, 17 Pure inductance, 17 Purkinje fiber action potential of, 9f resistance of, 8-9 Purkinje-myocardial junction, 203 Purkinje network, 203 Purkinje system, 203 Push-pull technique definition of, 618 failed antegrade/difficult retrograde LV lead placement, 679f-681f to gain guide support, 661, 661f venoplasty to avoid phrenic pacing and, 675f PVC PVARP extension, 822

Index

P-wave amplitude, 58 P-wave oversensing, 74, 75f P-wave tracking, 822f long PVARP causing in, 828f maximum tracking rate and, 826f P-wave undersensing, 827f

Q QRS activation, total, in heart failure, 208f QRS complex, 217f in children, 419 undersensing of, 875f, 878f QRS delay, heart failure and, 279 QRS duration, 218, 912 QRS notching, 929 QT interval, 146 Quality of life ICD shocks and, 258 ICD therapy and, clinical trials for, 257 pacing and, 314 product advisories and, 1038 Quarter pacing lead, 610 delivery guide support for, 612f QuickFlex 1156T OTW LV pacing lead, 610 QuickFlex Micro 1258 OTW LV pacing lead, 610, 611f-612f QuickFlex XL 1158T OTW LV pacing lead, 610, 610f QuickOpt clinical performance of, 967 for IACT estimating, 966f limitations of, 967-968 operating specifics for, 966 purpose of, 966

R Radial artery pressure, with atrioventricular block, 226f Radiated electromagnetic interference, 1004 Radiation therapy, heart block and, 335 Radiofrequency catheter ablation, 334 indications for, 1022-1023 Radiofrequency current, CIEDs and, 1023 Radiofrequency field effects of MRI on CIEDs, 1014b electromagnetic interference and in device circuitry, 1015 MRI and, 1015 pacing inhibition and, 1016-1017 Radiofrequency guidewire, for subclavian vein occlusion, 632-635 Radiofrequency identification technology (RIT), 1021 Radiography of abandoned leads, 791f of abdominal pacemaker/ICD systems, 773f-774f of abnormal LV lead placement, 784f-785f of atrial fibrillation lead system, 796f of azygos vein defibrillation lead, 797f of dextrocardia, 800f in child, 801f of epicardial RA/RV pacing lead, 790f of His bundle pacing, 787f of ICD pulse generator, 778f-779f of ICD with defibrillation leads, 775f of pacemaker/ICD pulse generators/ILR, 771 pacemaker implantation and, 486-487 of pacemaker lead conductor fracture, 791f

1077

Radiography (Continued) of pacing/defibrillator leads, 771-794 atrial lead positions, 780-781 coronary sinus lead positions, 782 epicardial lead positions, 782 pacemaker leads, 780-793 transvenous leads, 782f venous anatomy for localization of, 772 ventricular lead positions, 781 for pacing system malfunction, 867 of persistent left superior vena cava, 799f postimplantation, 806-807 complications from, 806-807 preprocedural chest, 771 pacing/defibrillation system, identification of, 771 patient anatomy, identification of, 771 of pulse generator, 776f-777f of single-lead VDD pacing system, 787f of ventricular pacing/atrial leads, 784f of ventricular pacing lead in RV outflow tract, 786f Radiotherapy, electromagnetic interference and, 1024, 1024b Ramp antitachycardia pacing, 379-380 Randomized controlled trial for atrial fibrillation and pacing mode, 244f, 246 Danish study as, 237 for dual-chamber pacing, 234 hospitalization for heart failure, 245f on pacing mode, 237 for sick sinus syndrome, 245 for sinus node disease, 245 Rapid depolarization. See also Depolarization Rapid exchange balloon, 623, 624f Rapidly conducted atrial fibrillation, 100f Rapidly conducted atrial flutter, 101f Rate-adaptive algorithm, 827 Rate-adaptive atrioventricular delay, 818 Rate-adaptive pacing mode, 156 for chronotropic incompetence, 827 sensors for, 144-156 for SND and chronotropic incompetence, 320 Rate-adaptive PVARP, 827 Rate-adaptive system, 158-170 curves used in, 145f design of, 145f Rate-adaptive ventricular pacing (VVIR), 234 dual-chamber pacing versus, 235t fixed-rate ventricular single-chamber pacing versus, 234, 235t VVI versus, 156 Rate burst pressure, of balloon, 625 Rate-drop response, heart rate and, 832, 833f Rate drop-responsiveness study blinded randomized studies McLeod Crossover Study, 368 Second Vasovagal Pacemaker Study (VPS-II), 368-369 Vasovagal Syncope and Pacing Trial (SYNPACE), 369 open-label randomized studies early termination of, 369 North American Vasovagal Pacemaker Study (VPS-I), 367 Vasovagal Syncope International Study (VASIS), 367-368 Rate drop-responsive pacemaker, 367

1078

Index

Rate drop-responsive pacing, 366t, 367 with dual-chamber programming, 370 Rate hysteresis, 367 Rate-modulated dual-chamber pacing system, laddergramming from, 853f Rate modulation, in pacemaker, 346 Rate profile optimization, 147, 148f Rate-related aberrancy, 93 morphology algorithm, error in, 94f Rate-response curve, 148f Rate-responsive pacing, 400-401 Rate smoothing, 367 algorithms for, 832, 832f AV pacing, leading to, 842f RD-CHF study, 252 Reactance, 5 capacitive versus inductive, 17 at electrode-electrolyte interface, 17 Real-time telemetry, 854 Rechargeable lithium-ion battery, 185-186 characteristics of, 185 end of service life, 186 method of recharge, 186 principles of operation, 185-186 Recommended replacement time (RRT), 846 RECOVER Study, 621 Rectus sheath, anatomy of, 497f Redetection, 83-85, 107f duration for, 108 SVT-VT discrimination in, 103-104, 108f Reduced battery voltage, 721 Reduction, 175 Reel syndrome, 791 Refibrillation, 49-53 Refractory period for AAI pacing, 400f for AAIR pacing, 400 biventricular pacing and, 840 for DDD(R) pacing mode, 65f events during, purpose of, 874-875 extension due to noise, 81f for pacemakers and ICDs, 61 relative versus effective, 8 sensing and, 60 total atrial, 823 ventricular, 813 Relative refractory period, 8 electromagnetic interference and, 1008 Relative risk reduction, for sudden cardiac death, 260 Reliability, of ICD therapy, 258 Remote monitoring. See also Automatic remote monitoring; Home monitoring for CIEDs databases for, 1001 implementation of, 992-999 manufacturer resources for, 989t medicolegal issues, 1002 patient-activated, 988-989 regulations for, 1002 service integration, 1001-1002 systems for, 988 technologic advances, 987-992 wand-based versus automatic, 990f device clinic implications and, 992-997 patient aspects of, 998-999 of pediatric pacemaker, 415-416 surveillance for, 997f

Renal failure drugs preventing ascorbic acid, 622 iloprost, 622 N-acetylcysteine, 621-622 sodium bicarbonate, 621 hemofiltration and hemodialysis for, 622 RENEWAL-AVT, 292 concomitant conversion in, 292f RENEWAL Study, 292-293 Repetitive non-reentrant ventriculoatrial synchronous rhythm definition and cause of, 884 management of, 884 Replacement therapy, 1041-1042 Repolarization cardiac action potential and, 7 final, 8 initial, 8 cardiac memory and, 210-211 cause of, 8 re Quinlan, 1040 Resistance, 4, 846-847 voltage and delivered capacity, relationship between, 180f Resistor-capacitor (RC), 42, 43f Resting membrane potential, 7 Resting transmembrane potential, 5-6 Restitution curve, 41f Restitution hypothesis, of ventricular fibrillation, 41 Resynchronization/Defibrillation for Advanced Heart Failure Trial (RAFT), 273 Resynchronization for the Hemodynamic Treatment for Heart Failure Management (RHYTHM II ICD) study, 961-963 Resynchronization lead, 134-136 pacing polarity configurations for, 136f placement and fixation mechanism for, 135-136 types of, 135f Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction (REVERSE), 295t hazard ratios in, 289f for heart failure prevention, 289 Resynchronizer, 223 Retention wire, axillary vein venogram of, 533f Retrograde atrial activation, 58-59 Retrograde microdissection, of total occlusion, 634f Reverse remodeling, 917-918 Reverse volumetric LV remodeling, 917-918 baseline/post-CRT predictors of, 929f cardiac resynchronization therapy and, 927-943, 928f global measure of ventricular fusion predicting, 929f Revised pacing system code, 813 Rheobase, 13-14, 13f, 42 Rheobase voltage, pacing rate and, 15f Right anterior oblique (RAO), 507, 508f coronary sinus in, 509f image of, 512f Right atrial appendage lead, 511f Right atrial pacing effect on AV electromechanical timing, 951-952, 952f effect on multi-chamber timing, 951, 952f selective sites for, 509

Right atrium characteristics of, 505f composite illustration with guide in, 545f HCN4 protein in, 303f Koch’s triangle landmarks on, 507f selective site pacing and, 506 view of, 506f Right bundle branch (RBB) anatomy of, 323 trifascicular block and, 326-327 Right bundle branch block (RBBB), syncope with and AV block, tracings from, 336f Right-sided heart bypass, 393 Right ventricle anteroposterior view of, 512f characteristics of, 507 composite illustration with guide in, 544f dissection opening of, 507f Right ventricular activation, in heart failure and LBBB, 220f Right ventricular activation time (RVAT), 929 calculation using surface ECG, 930f Right ventricular apex pacing, 209f Right ventricular apical pacing, 316 atrial fibrillation and, 503 in atrioventricular block, 350 effects of, 316t harmful effects of, 350 ventricular activation sequence and, 936 Right ventricular based timing biventricular pacing with competitive pacing and, 841f LV refractory extension and, 841f Right ventricular capture, 923-925 Right ventricular outflow tract (RVOT), 218, 352 RV selective site pacing and, 510 Right ventricular outflow tract pacing, 218 Right Ventricular Outflow versus Apical Pacing (ROVA) trial, 352 Right ventricular pacing, 156, 838f abnormal activation sequence during, 206 biventricular pacing versus, trials evaluating, 252-253 in children, effects of, 217 hemodynamics and, 833-834 local energetic efficiency, effect on, 207-209 unnecessary, role of prevention in, 250-251 Right ventricular pressure, 161-162 sensor measuring, 157f Right ventricular pressure waveform, in real time, 162f Right ventricular selective site pacing, 510 Right ventricular sensing heart failure, measuring pressure in, 157f with positive RV-LV interval, 839f with premature LV extrasystoles, 838f Right ventriculotomy, for lead extraction, 768 Ring-coil impedance, 891f Risk Estimation Following Infarction Noninvasive Evaluation–ICD Efficacy (REFINE-ICD), 274, 275t Ritter method, 944-945, 945f summary of, 946f Rolling threshold, 147 Runaway pacemaker definition of, 879 example of, 879f



R-wave double-counting, 66, 74, 86f-87f cause of, 75f

S Safety adequate margin of, 34-35 autosensing for, 66f with high-power batteries, 184-185 Safety alert, 1033 Safety output pulse crosstalk and, 878 delivery effects of, 878-879 Safety pacing, crosstalk and, 878f Salt/fluid, for vasovagal syncope, 365 same-chamber blanking period, short, 66 Sarcolemma, 8 Sawtooth effect, 18 Sawtooth model, 45-46 minimum potential gradient and, 46 of transmembrane potential during shock, 46f Scatter radiation, 1024 Schiavo, Terri, 1040 ScoutPro ACS Introducer System, 591f Scrub nurse/technician, for pacemaker implantation, 444 SDAAM, 159-160, 161f SDANN, heart rate variability and, 159 Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) trial, 317-318 Search AV hysteresis, 316 Search hysteresis, 835 Secondary source model, 46-47 computer mode of, 46f Second-degree AV block, 330 Second Dual Chamber and VVI Implantable Defibrillator (DAVID-II) trial, 272 Second-generation locking stylet, 761 Second-generation multisite pacing pulse generator, 922 Second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II), 248, 257 ICD shocks and, 258 for ICD therapy, 264-266 criteria, comparison groups and results, 264t population details/mortality results, 265t RVA pacing and, 350 Second Thrombolysis in Myocardial Infarction (TIMI II), 338 Second Vasovagal Pacemaker Study (VPS-II), 368-369 outcome of, 369 Sedation, for pacemaker implantation, 452 conscious, protocols for, 452t Seldinger technique, 457 Selective serotonin reuptake inhibitor, for vasovagal syncope, 366 Selective site pacing considerations for, 505 future of, 512 for ICD implantation, 503-512 radiographic anatomy and, 507-509 for right atrium, 509 right atrium and, 505-507 right ventricle and, 507 Selectsite steerable catheter, 505f Selectsite steerable stylet, 505f

Index

Selectsite snare approach, to transseptal left ventricular lead placement, 703f-706f Self-contained intracardiac pacemaker, 434-439 Self-discharge, of battery, 177-178 Selvester QRS score, 929 Senning procedure for congenital heart disease, 797 pacemaker system in DTGA after, 803f pacemaker system in LTGA after great arterial switch procedure and, 804f pediatric transvenous ICD system implanted after, 803f Sensed atrial event, 818 Sensed event, 56 Sensing, 56-126 in cardiac resynchronization ICDs, 68 concepts of, 60 event detection and certification phases of, 117 failure of, 874-876 in ICD lead, 137-138 long-term leads for, 727-728 minute ventilation, 149-150 occurrence of, 62f in pacemakers and ICDs, 60-68 parameters for, 146 postshock, 67 refractory/blanking period and, 874-875 subcutaneous ICD and, 117 with subcutaneous lead, 431 in surface electrocardiogram, 62f tachyarrhythmias detection and, 117 of ventricular electrograms, 66-67 of ventricular fibrillation, 64 evaluation at implantation, 67 Sensing integrity counter (SIC), 75 Sensing latency, 949 effect on EGM timing to electrical activity, 951, 951f Sensing threshold EGM peak-to-peak measurement as, 853-854 in pacemakers, 62 pacing system malfunction and, 867 Sensing-threshold voltage, 60 Sensitivity automatic adjustment of, 64-65, 66f in ICDs, 67f methods of, 64 in normal rhythm, 64 postpacing, 64f of automatic mode switching algorithms, 82f Sensor. See also Implantable sensor for heart failure, 158-170 activity monitoring, 159 heart rate variability, 159-160 types of, 158t for rate adaptation, 158 Sensor blending, 152 Sensor cross-checking, 152 Sensor-driven appearance, of atrial tracking, 826f Sensor-driven atrial stimulus, P wave inhibiting, 826f Sensor-driven pacemaker, 147-149 Sensor-driven pacemaker tachycardia causes of, 879b occurrence of, 879-880 Sensor-driven pacing, 144, 825-827 benefits of, factors affecting, 154-156, 155t rate-adaptive pacing modes for, 156

1079

Sensor-driven pacing (Continued) timing cycles of, 827 upper-rate limit and, 156 ventricular pacing site and, 156 Sensor-driven rate smoothing, 823 Sensor-indicated heart rate histogram, 857f Sensor rate profile, 147, 148f Separator, of battery, 176 Sequential R-L ventricular activation despite simultaneous BiV pacing, 961f LV capture latency causing, 961f LV capture latency/differential paced activation wavefront conduction times, 962f during simultaneous BiV pacing, 964f Sequential ventricular stimulation, 961-963 Sequential ventricular timing in CRT, implementation of, 959-961 Series circuit, 4 Service kit, for pacemakers, 446, 447b Sheath removal of, 579f-580f lead length and, 581f Shock. See also Multiple shocks causing refibrillation, 49-53 defibrillation success and, 40 electrode placement and, 43 ICD therapy limitations and, 258 inappropriate for AF in Brugada syndrome patient, 389f morbidity of, 904 lead fracture causing, 723f parameters for, 42-43 phase maps of, 44f postshock activation after failure of, 52f postshock cycles after failed and successful shocks, 51f after failure of, 50f sawtooth model of transmembrane potential during, 46f supraventricular tachycardia after, 93-95 ventricular fibrillation from, 377f waveform, altering strength of, 45 Shock coil ingrowth, 141f Shock-induced phase singularity, 48f Shocking electrode, in right ventricular apex, 498f Shock waveform components of, 374 pulse width and, 375f Short balloon for SVC-innominate vein junction occlusion, 652 total occlusion dilation with, 652f Short QT Syndrome, 384 risk stratification for, 384 therapeutic recommendations for, 384 ICD therapy, 386t Sick sinus syndrome cardiac pacing and, 393 concomitant symptomatic heart block and, 334 electrocardiogram from, 394f single-chamber pacing for, 398 single-lead atrial versus dual-chamber pacing in, RCT for, 245 Sigmoid coronary sinus preventing guide advancement, 564f with previous mitral valve repair, 562f

1080

Index

Silicone rubber, 130 insulation failure, mechanisms of, 131f Simultaneous BiV pacing despite sequential R-L ventricular activation, 961f LV capture latency causing, 961f LV capture latency/differential paced activation wavefront conduction times, 962f during sequential R-L ventricular activation, 964f Simultaneous electrocardiogram, rhythm strip and event markers for, 848f Simultaneous LV sensing, double-counting and, 978 Simultaneous RV sensing, double-counting and, 978 Single-chamber atrial building blocks, 88 purpose/weaknesses of, 89t Single-chamber discriminator, 96 Single-chamber ICD SVT-VT discrimination in R-R interval regularity, 88 sudden onset, 88-90 ventricular electrogram morphology, 90 Single-chamber pacing with event markers, method for, 851 mode, rate, parameter change, cause of, 866, 866b runaway pacemaker in, 879 timing cycles and, 813-816 SSI mode, 813 ventricular blanking and refractory periods, 813 VVI mode, 813-815 venous access for, 468b Single-chamber ventricular building blocks, 85 purpose/weaknesses of, 89t Single-chamber ventricular demand (VVI), double-blind crossover studies for, 239-243 Single-chamber ventricular pacing, electrode system for, 398-399 Single-coil transvenous defibrillator system, 419, 421f Single-lead atrial pacing, sick sinus syndrome and, RCT for, 245 Single-lead VDD pacing dual-chamber DDD pacing in atrioventricular block, 235 radiography of, 787f Sinoatrial nodal cell, 7 Sinus bradycardia, lower rate limits and, 223-224 Sinus node action potential of, 9f anatomy of, 323 HCN4 protein in, 303f mRNA in, 302f Sinus node disease. See also Atrial fibrillation; Thromboembolism AAIR versus DDDR, RCT for, 245 atrial versus ventricular single chamber pacing in, 237-238, 237t bipolar voltage mapping in, 304f cardiac pacing and, 234 chronotropic incompetence and rate-adaptive pacing, 320 clinical outcomes in, 305-306 course of, 305

Sinus node disease (Continued) diagnosis of, 305, 305t electrocardiographic manifestations of, 300 mortality relating to pacing mode, 238t pacemaker diagnostics for, 306-313, 306f pacemaker syndrome and, 234 pacemaking mechanisms in, 301f pacing for, 300-322 indications for, 318t pathophysiology and diagnosis of cellular electrophysiology, 300 clinical electrophysiology, 300 physiologic pacing mode and, 319f symptoms of, 304-305, 305t treatment of AAIR pacing, 318-320 pacing modalities, 318-320 Sinus node dysfunction. See also Sick sinus syndrome managed ventricular pacing in, 398 permanent cardiac pacemaker for, 393 Sinus rhythm auxotonic relaxation and, 209 electrical activation during, 203-204 failure to detect, 108f mechanical activation during, 204-206 pressure-volume diagrams during, 210f Sinus tachycardia, 388f Site preparation, for pacemaker implantation, 450-451 Situs LDS-2 lead delivery system, 593f Slew rate, 56-59 definition of, 852 of electrogram, 58 exercise effect on, 58 during retrograde atrial activation, 58-59 undersensing and, 58 SmartDelay optimization, 963-966 clinical performance of, 966 limitations of, 966 operating constraints of, 965-966 operating specifics for, 963-964 Snare Byrd Femoral Workstation, 762f clinical circumstances for use of, 698 for left ventricular lead implantation, 695-699 types of, 698f ten-mm single loop system, use of, 698f use and types of, 761 Social-environmental factors, children with pacemakers and, 423 Sodium bicarbonate, 620 for renal failure prevention, 621 Sodium channel, 7 Sodium channel gene, 332 Sorin Group pacemaker, 34 Sorin Parad+ algorithm, 104f Special procedures room, for pacemaker implantation, 444 Specific absorption rate (SAR), 1004 Specificity, of automatic mode switching algorithms, 82f Speckle tracking, 221-222 Spinal cord stimulation, 1018 Split-cathodal configuration, 33 Spontaneous conduction block, implication on BiV pacing, 958-959

Spontaneous ventricular arrhythmia ICD therapy clinical trials for, 261-264 criteria, comparison groups, and results, 262t population details/mortality results, 262t Spontaneous ventricular depolarization, 822 Square waveform, 42, 45 effects of, 45f SSI pacing, 813 Stab-in electrode, 405 Stacked-plate aluminum electrolytic construction of, 187-188 cutaway view of, 188f Standard IS-1/DF-1 dual-coiled ICD header, 199f Standard IS-1/DF-1 dual-coiled ICD lead, 198f Staphylococcus aureus, 452 Staphylococcus epidermis, 452 Staphylococcus species, CIED implantation infections and, 744-746 StarFix lead, 608 in target vein, 609f START study, 117 Static current drain, 179 Static electrical charge, 3 Static magnetic field, 1004 effects of on generator, 1014 MRI on CIEDs, 1014b Stenosis, view of, 752f Stenotic coronary sinus lateral wall vein and, RAO view of, 550f-551f preventing guide advancement, 564f Stent, coronary vein, straightening of, 683f-684f Steroid-eluting electrode, 30-31 acute implantation voltage and current threshold for, 406f acute thresholds for, 408f in children, 405-406 threshold for, 406, 406f-407f Stimulation anodal and cathodal, 11-13 electric potential gradients/currents for, 10-11 Stimulation impedance, 846-847 importance of, 866-867 Stimulation threshold, 13 antitachycardia/bradycardia pacing and, 15 electrode design effect on, 31-32 glucocorticoids effect on, 33 mechanism of fixation effect on, 31 metabolic effects on, 32 pacing rate effect on, 15 pharmacologic effects on, 32 strength-duration relationship and, 14 St. Jude A-V Rate Branch, 102f St. Jude CS access catheter, 596f St. Jude Medical activity-sensing device, 147-148 rate-response curve and “auto” slope in, 148f St. Jude Medical delivery guide, 597f St. Jude Medical ICDs, Automatic Gain Control for, 65 St. Jude Medical Model V193 ICD, 889-890, 890f St. Jude Medical Model V242 ICD, 889-890, 891f St. Jude Medical over-the-wire LV pacing lead types of, 610, 610f QuickFlex 1156T, 610 QuickFlex Micro 1258, 610, 611f-612f QuickFlex XL 1158T, 610, 610f



St. Jude Medical pacemaker autocapture fusion avoidance in, 355f automated capture features of, 34 Stokes-Adams attack, 329 Complete heart block (CHB) and, 330 Strength-duration curve, 13, 13f-14f for defibrillation, 375f logarithmic plots of, 25f in pacing, 374 stability of, 28 Strength-duration relationship, 13-15, 13f battery longevity and, 35, 35f stimulation threshold and, 14 Strength-interval curve, 16f Strength-interval relationship, 15-16 Stroke impedance, 168-169 Stroke index, changes to, 398f Stroke. See Thromboembolism Structural cardiac disease, CRT therapy for, 421-423 ST-segment shift, 170 Study of Atrial Fibrillation Reduction (SAFARI) trial, 310 Stylet characteristics of, 579-585 LV pacing lead dislodged by, 585f removal of, 579-585 Subclavian clavicle-first rib crush syndrome, 791, 792f Subclavian crush phenomenon, 458 Subclavian/innominate occlusion, crossing, 625-646, 628f Subclavian/innominate venoplasty, 647-653 complications of, 653 deceptive wire location, 655f dilation of occlusion, 650f training required to perform, 653-655 Subclavian vein, 454 Byrd’s technique for access to, 459-460, 460f location/deformities of, 455-456 Subclavian vein approach, for endocardial electrode implantation, 410 Subclavian vein occlusion (stenosis) contrast injection into revealing opening, 627f revealing total occlusion, 627f crossing, 626-627 system for, 628f defining obstruction, 626 dilation of, 649f dilator for, 650 injection system for defining, 626f peripheral venography of, 781f predilation with coronary balloon, 651f preexisting leads and, 625-646, 626f progressively large dilators, hemodynamic collapse using, 648f radiofrequency guidewire for, 632-635 subclavian venoplasty versus progressively large dilator, 646-655 venoplasty equipment for, 647b venous access without pacing leads, 642f-643f Subclavian venipuncture Magney approach to, 461f pneumothorax from, 470 using contrast venography, 464, 464f

Index

Subclavian venoplasty balloons for, 647-652 coronary balloon for, 647-650 elements of, 656b progressively large dilators versus, 646-655 staining and, 655f Subclavian venous access, for transvenous pacemaker placement, 457-459 Subclavian window, 457, 457f Subcutaneous defibrillation electrode, 497-498, 498f Subcutaneous electrocardiogram, 116-117 Subcutaneous electrocardiography, 59-60 Subcutaneous electrode/lead, sensing with, 431 Subcutaneous emphysema, 872 Subcutaneous ICD. See also Implantable cardioverter-defibrillator (ICD) crossing angled hydrophilic catheters for, 628f curved generator/electrode for, 428, 429f defibrillation threshold for, 430f early investigation experience with, 428 electrode system for, 121f future of, 432-433 history/background of, 428 lead and pulse generator location for, 500f locations for components in situ, 431, 431f optimal defibrillation configuration for, 428-430, 430f parasternal electrode for, 430f programming screen for, 432f sensing and, 117 sensing vector for, automatic selection of, 121f Subcutaneous patch/coil/array, 803 Subcutaneous tunneling, 484f Subeustachian space, composite illustration with guide in, 546f Submuscular pectoral pouch, 501-503, 502f anterior axillary line, 502f Subpectoralis muscle approach, for ICD implantation anterior, 502f anterior axillary fold, 503f deltopectoral groove and, 502f Substitutive therapy, 1041-1042 Subsystem performance counter, 856-858 Subxiphoid approach for epicardial electrode implantation, 409 for ICD implantation, 494, 494f Sudden cardiac death definition/implications for clinical trials for, 257 individual risk versus population impact of, 259-260, 259f specificity versus sensitivity, 260f relative versus absolute risk reduction for, 260 risk groups for, 259-260 Sudden Cardiac Death Heart Failure Trial (SCD-HeFT), 257 ICD shocks and, 258 for ICD therapy, 266-267 criteria, comparison groups and results, 264t population details/mortality results, 265t tachyarrhythmia therapy and, 379 Superior mediastinum, anatomic structures of, 454f Superior vena cava, lead extraction and, 752

1081

Superior vena cava-innominate vein junction occlusion dilation of long versus peripheral balloon, 651f short balloon for, 652 Superior vena cava occlusion, 640f laser opening of, 641f Support group, for children with pacemakers/ICD, 425 Supraventricular arrhythmia, multiple shocks and, 902 Supraventricular tachycardia atrial proarrythmia caused by, 105f detection as diagnostic tool, 112-116 inappropriate classification of, 95 rejection of, 97f after shock, 93-95 ventricular antitachycardia effect on, 106f ventricular therapy for, 104 Surface electrocardiogram, 56, 876f of intrinsic beats and PVC, 876f RV/LV activation time calculation using, 930f sensing occurrence in, 62f simultaneous event markers and, 850f Surgeon for ICD and CRT implantation, requirements for, 491-492 for pacemaker implantation, 443-444 Surgical epicardial LV lead placement, 518 for biventricular pacing, 518f equipment for, 613 safety with, 518 transvenous versus, 611-613 Surgical epicardial LV pacing indications for, 611-613 open-heart surgery, 611 unsuccessful percutaneous insertion, 611 Surgical lead extraction approach, 767-769 open-heart procedure, 768-769 right ventriculotomy as, 768 transatrial approach to, 767-768, 768f Surgically induced heart block, 393, 394f incidence of, 394f permanent cardiac pacemaker for, 394 structural cardiac defects associated with, 394t Surgical smoke cause and prevention of, 480 risks associated with, 480b Surveillance of device performance, 1031-1034 post-market goal of, 1031 methods of, 1031-1032, 1031t for remote monitoring, 997f Survival rate with atrioventricular block in relation to pacing mode, 239t with sinus node disease in relation to pacing mode, 238t SVT-VT discrimination, 85-104 algorithms for, measuring performance of, 104 inappropriate detection/therapy/shocks, 104 quantitative considerations, 104 in dual-chamber and cardiac resynchronization ICDs, 95-96 programming for, 109, 109t dual-chamber discriminators, 109 single-chamber discriminators, 109

1082

Index

SVT-VT discrimination (Continued) range of cycle lengths for, 109 in redetection, 108f during redetection, 103-104 in single-chamber ICDs R-R interval regularity, 88 sudden onset, 88-90 ventricular electrogram morphology, 90 SVT-VT discriminator, 111 Synchronous ventricular activation, 914f Synchrony, 911 Syncope. See also Carotid sinus syncope; Vasovagal syncope AV block with incomplete RBBB, tracings from, 336f cardiac pacing as treatment for, 234 definition of, 361 electrophysiologic study for, 328, 331t Long QT Syndrome and, 383 recurrence with/without pacemaker, 370f closed-loop simulation, 371f in VASIS, 368f in VPS-I, 367f in VPS-II, 368f Syncope Diagnosis and Treatment Study (SYDAT), 368 Systolic function, asynchronous activation effect on, 209-210 Systolic impedance, 168-169

T Table positioning for device implantation importance of, 623f Table. See Implant table; Instrument table Tachyarrhythmia anodal stimulation generating, 23 electromagnetic interference and, 1008 sensing and detection of, 117 Tachyarrhythmia detection building blocks, 89t Tachyarrhythmia therapy, at ICD postimplantation, 379-380 Tachycardia classification of, 99f pseudo-ventricular, 879, 879f Tachycardiac episode, 79-82 Tachycardia discrimination, 98f atrial rate equal to ventricular rate, 96t atrial rate greater than ventricular rate, 97t Tachysystolic stage, of ventricular fibrillation, 40 Talent DDDR, 169-170 Tamponade, lead extraction and, 752 transvenous approach and, 765 Tantalum electrolytic capacitor construction of, 188 cutaway view of, 189f Target rate profile, 147, 148f Task Force on Lead Performance Policies and Guidelines, Heart Rhythm Society (HRS), 1031 Telemetered bipolar ventricular electrogram, 853f Telemetry, 848f definition of, 844 electromagnetic interference and, 1010 of event markers, 849-852 for ICD malfunction, 889-891 for lead impedance, 848 limitations of, 860f measured data, 847f

Tendon of Todaro, 506-507 Tetralogy of Fallot, 797 ICD lead positioning in, 804f Therapeutic current, 179 Therapeutic magnet, electromagnetic interference and, 1013 Thermistor, 146 Third-generation lock stylet, 761, 762f Thoracoscopic approach, for ICD implantation, 495 Thoracotomy, endocardial lead placement during, 487f-488f Thorax, anatomic structures of, 453 Three-position ICHD pacemaker code, 195, 196t, 813 pacing modes described by, 196t Threshold voltage, 7 Thromboembolism atrial/dual-chamber pacing versus ventricular single-chamber pacing, 239 atrial fibrillation risk and, 313-314 occurrence of, 313 pacing mode and mortality, studies on, 239t transseptal LV lead implantation approach and, 517-518 Thrombolytic therapy, 341-343 Thrombosis, lead extraction and, 751-752 Tiered-therapy ICDs, 83 Tilt, 42-43 Tilt-table test, 365 Time-based system performance counter, 858 Timing cycle in biventricular pacing, 837 goals of, 836-837 definition of, 813 diagrammatic representation of, 828f in dual-chamber pacing modes, 836 DDI mode, 835-836 VDD mode, 835, 836f VVT and AAT modes, 836 ICD, pacing algorithms in, 841-842 of implantable devices, 813-843 of sensor-driven pacing, 827 single-chamber pacing and, 813-816 SSI mode, 813 Tissue debridement, 754 Total atrial refractory period (TARP), 61, 823, 824f PVARP and AVI, 826f Total endocardial activation, in heart failure, 208f Total occlusion dilation with short balloon, 652f directed needle catheter for, 636f laser crossing of, 635-639 limitations of, 638 orthogonal view, 639f microdissection of, 634f Frontrunner XP CTO Catheter for, 632, 633f Success, 632 retrograde microdissection of, 634f sites for, 650f without implanted leads, 639-646 without pacing leads to follow, 644f-646f Total QRS activation, in heart failure, 208f Total reactance, 17 Total system performance counter, 855-856 Touhy-Borst valve, wire inserted through, 547f-548f

Traction definition of, 755 direct, 755-756 indirect, 756 Transaortic ICD implant, lead extraction, 753f Transatrial endocardial atrial pacing, in congenital heart disease, 487f Transaxillary retropectoral pacemaker implantation, 485f Transclavicular tunneling, 482 Transcutaneous electrical nerve stimulation (TENS), 67 indications for, 1018 shocks from, 1018 Transcutaneous pacing, endocardial electrode implantation and, 409-410 Transdiaphragmatic approach, for ICD implantation, 495 Transhepatic cannulation, 489 Transhepatic lead implantation, 490f Transient hypotension, vasovagal syncope and, 364-365 Transiliac ICD implantation, 500 leads tunneled in, 501f Transitional cell zone, 323 Transjugular intrahepatic portosystemic shunt set (TIPS needle), 635 Transmember potential after biphasic shock, 48f cellular action potential and, 48 changes in, in cardiac pacing/defibrillation, 17-18 sawtooth model of, 46f Transmember voltage, 9 mechanism of change in, 18 Transmitral pressure gradient, 938 LV inflow velocity pattern changes and, 941f Transseptal activation delay, 913 Transseptal activation time, 206 in heart failure, 208f Transseptal left ventricular lead pacing, 517-518 Transseptal left ventricular lead placement, 700-701, 701f-702f modified Elencwajg-Cardinal femoral approach to, 707f-710f Selectsite snare approach to, 703f-706f Transtelephonic monitoring for CIEDs, 988 of pacing system, 885 of pediatric pacemaker, 415-416 Transthoracic defibrillator implantation, 11 Transthoracic impedance, 146 Transvenous access venography, 801 Transvenous electrode implantation, 410 Transvenous endocardial lead placement. See Endocardial lead placement Transvenous ICD system, high defibrillation thresholds and, 793, 795f-796f Transvenous lead bulk in pocket of, 736f radiographic appearance of, 782f Transvenous lead extraction. See also Lead extraction indications for, 750b Transvenous lead extraction approach complications from, 764-765 cardiac tamponade, 765 wall integrity, loss of, 765



Transvenous lead extraction approach (Continued) through femoral vein, 766-767 through lead vein entry site, 764-765 through remote vein sites, 765-766 through superior vein, 767 Transvenous LV pacing lead, as unipolar or bipolar, 920 Transvenous pacemaker system, in subpectoral position, 772f Transvenous pacing, contraindications for, 485-486 Transvenous permanent pacemaker implantation approach, 453 cephalic venous access for, 456-457 in infants and children, 485-486 subclavian venous access for, 457-459 Transvenous permanent pacemaker lead placement, 464 Treadmill exercise, 153f Treatment refusal, patient’s right to, 1040 Tremulous incoordination stage, of ventricular fibrillation, 40, 41f TRENDS study, 314 Tricuspid annulus, composite illustration with guide at, 545f Tricuspid valve, 507 Trifascicular block, 326-327 Trifascicular conduction system, 203 Triggered pacing mode, VVT and AAT, 836 Triphasic rate-response curve, 147, 147f True atrial undersensing, 968 Truncated exponential biphasic waveform, 42 TRUST trial, 989-992 objective of, 989-990 results for, 992f study design for, 991f Tunneling pacemaker system upgrade and, 477 Penrose drain and lead for, 477f subcutaneous, 484f techniques for, 477-478 transclavicular, 482 Tunnel propagation, 49 T wave, prevention of pacing on, 971 T-wave oversensing, 64, 64f, 69-74, 72f, 86f-87f bipolar signal preventing, 73f classification of, 71, 72f correcting, programmable features for, 73f reduction of, 71-74 rejection of, 74f Twiddler’s syndrome, 501, 729f cause of, 791, 864 lead failure in, 891-892 radiographic view of patient with, 793f Twiddling, 896f Two-dimensional bidomain model, 47f

U Ultrasound energy converter, 437, 438f Ultrasound pacing, 436-437 acoustic window for, 437, 437f investigational equipment of, 436f oscilloscope recording during, 437f transmission and focusing of, 439f Ultrasound technique, for axillary venous access, 462-463, 463f-464f Uncoupling consequences of

Index

Uncoupling (Continued) at atrial level, 911 at atrioventricular level, 911 Underdetection cause of, 109-112 of ventricular fibrillation, 110f Undersensing in atrium, 64f cause of, 58, 109-112, 874b effects of, 56 pacing system malfunction and, 875 of QRS complex, 878f with AF, 875f ventricular, 814 of ventricular fibrillation, 109, 111f VT induction and, 902-904 of VT/VF, 66 Undulatory stage, of ventricular fibrillation, 40, 41f Unidirectional block, 48 Unipolar atrial lead, IEGM from, 869f Unipolar electrode system, 56 spatial/temporal relationships for, 57f Unipolar electrogram, bipolar electrogram versus, 61f Unipolar impedance from right ventricle, 168 Unipolar lead, 127 insulation failure, effect of, 128 stimulation threshold of, 127-128 Unipolar pacing circuit, 128f Unipolar pacing lead, 614f Unipolar pacing system, 16, 728f bipolar pacing versus, 404-405 biventricular sensing and, 840f electrode sensing for, 405f implantation thresholds for, 405f Unipolar split-cathodal configuration, 33 Unipolar stimulation, 23-24 Unipolar ventricular impedance, 168 closed-loop simulation sensor and, 150-151 United Kingdom Pacing and Cardiovascular Events (UKPACE) Trial, 242-243 clinical events in, 242t critical appraisal of, 242-243, 249 intolerance to VVI(R) in, 250f Univentricular pacing, biventricular sensing with, 839 Universal Slitter and guide hub, 582f-583f CPS, 597f Upper limit of vulnerability (ULV) method, 378 Upper rate behavior, 822-823, 823f purpose of, 839-840 Upper rate interval (URI), 824f Upper rate limit, 156 Upper-rate set point, 147 Usable energy density, 178 U.S. Joint Commission on Accreditation of Health Care Organizations, 452 Utilization, of ICD therapy, 259

V Vacco v. Quill, 1041 Vagally mediated AV block, 336 Vasopressor, for vasovagal syncope, 366 Vasovagal syncope bradycardia, evidence for, 365 implantable recorder, 365 loop recordings, 370

1083

Vasovagal syncope (Continued) pacemaker memory, 365 tilt-table test, 365 clinical perspective for, 364 epidemiology, 364f evolving technology for, 370-371 management of, 365t medical therapy for beta-adrenergic blocker, 366 Fludrocortisone acetate, 366 rate drop-responsive pacemaker, 367 RCTs for, 366, 366t selective serotonin reuptake inhibitors, 366 vasodepressors, 366 occurrence of, 361 pacing for, 364, 365t benefits of, 366-369 clinical trials of, 369 guidelines for, 371 observational studies, 367 patient selection for, 369-370 rate drop-responsive, 366t, 367 sensors of transient heart rate decrease, 367 physiology of, 364-365 symptoms and QOL for, 364 transient hypotension and, 364-365 treatment of, 365-366 physical counterpressure maneuvers, 365-366 reassurance and education, 365 salt and fluids, 365 Vasovagal Syncope and Pacing Trial (SYNPACE), 369 outcome of, 369 Vasovagal Syncope International Study (VASIS), 367-368, 368f VDD mode, 836f VDD pacemaker, 347f VDD pacing, 219t timing cycle in, 835 VDD(R) pacing, 347 VDD system electrode placement for, 347 implantation of, 347 pacemaker programming of, 348 radiography of, 787f reliability of, 347 complications versus, 347 VDI pacing mode DDI mode versus, 836 timing cycle in, 836 Vegetation, echocardiography diagnosing, 808, 808f Vein, pacing lead-induced perforation of, 590f Vein laceration, 695 Vein rupture, 695 Vein selector, 516 CS access catheter and deploying through, 568 loading into, 571f definition of, 618 failure to cannulate target vein, 569f functions of, 516 injection system and, 572f removal of, 572 renal-shaped delivery guide with, 528f shape of, 568 in tortuous vein, 570f

1084

Index

Vein selector (Continued) types of, 517f hook, 573f standard versus hook, 576f Velocity time integral (VTI), 947 aortic, pacemaker AVI change effect on, 926 Venography device implantation and, 801-806 device replacement and, 729 indications for, 729 venous occlusion and, 729f Venoplasty, 675f for additional LV lead placement, 666f angioplasty balloon versus inflation pressure for, 623-625 of branch vein, 676f of collaterals between veins, 671-681 contrast injection after with previous cardiac surgery, 685f-686f without previous cardiac surgery, 689f failure of edema or clot formation, 660, 660f lack of guide support, 658f using CS access catheter, 659f Kevlar balloon and, 652f after LV lead displacement, 667f-670f after LV lead implantation, 664 of main coronary sinus, 662-664 after open-heart surgery, 671f phrenic pacing and, 671, 674f push-pull technique, 675f of small/stenotic target vein, 664-671 without open-heart surgery, 672f-673f with stent placement, 681 success of, 659f procedures and techniques ensuring, 660-662 training required to perform, 653-655 venous integrity loss with, 681 Venoplasty balloon, preparation of, 626b Venous access sacrificing lead for, 629-632, 632f of total subclavian occlusion, without leads, 642f-643f Venous angioplasty, endocardial electrode implantation and, 410 Venous occlusion, 729f Venous stenosis, lead extraction and, 751-752 Ventricle loading condition, effects of change in, 938, 940f Ventricular activation, 205 anodal capture effect on, 925f characterization during LBBB using QRS hieroglyphics, 928-929 during lateral cardiac vein pacing, 932f LV only effect on LV strain map and, 934f LVO pacing effect on LV strain map and, 935f during middle cardiac vein pacing, 932f during monochamber LV pacing, 931, 931f reverse volumetric LV remodeling, predicting during CRT, 928f RVA pacing and, 936 during sequential BiV pacing at shortened AVD, 938f Ventricular activation time, 951f

Ventricular activation wavefront fusion achievement/confirmation of, 952 during biventricular pacing, 939f CRT after, 933f CRT during, 927-929, 931, 933f as CRT translational mechanism, 952 incomplete, during simultaneous biventricular pacing, 937f Ventricular antitachycardia pacing atrial proarrythmia caused by, 105f supraventricular tachycardia, effect on, 106f ventricular tachycardia, atrial response to, 106f Ventricular arrhythmia EGM displaying, 890f ICD therapy clinical trials for, 261-264 criteria, comparison groups, and results, 262t population details/mortality results, 262t Ventricular asynchrony, heart failure and, factors contributing to, 914 Ventricular asystole, 211 Ventricular-based timing, 823-825 Ventricular-based timing cycle, 829f DDD mode with, 828f Ventricular blanking period, 813 Ventricular Capture Management feature, 34 Ventricular capture threshold, voltage output and, 925 Ventricular capture verification, 79 Ventricular conduction, atrial tachyarrhythmia with, 971-973 Ventricular conduction block, 952-953 ventricular activation wavefront fusion challenges, 958-959 Ventricular conduction delay asynchronous heart failure caused by, 913-917 mechanical dyssynchrony inducing, 916f Ventricular contraction, 205 Ventricular depolarization, far-field R wave and, 57-58 Ventricular double-counting, 968 elimination of, 979 loss of CRT from, 969f of nonsustained VT in nondedicated CRT-D system, 980f reduction of, 968-970 simultaneous RV and LV sensing causing, 978 during VT on stored EGM in nondedicated CRT-D system, 981f Ventricular electrode, placement of, 470-474, 470f stylet placement/withdraw, 474, 474f suture sleeves to secure, 474, 474f through persistent left superior vena cava, 489f Ventricular electrogram (VEGM) amplitude of, 56 atrioventricular pacing and, 216f current of injury, 58 in heart failure patient, 217f during premature ventricular complex (PVC), 58 recording of, 59f sensing cycle lengths of, 68f sensing occurrence in, 62f, 66-67 Ventricular electrogram morphology for SVT-VT discrimination limitations of, 90-95 steps for, 90-95, 90f types of, 91f

Ventricular electromechanical resynchronization, 927-931 Ventricular escape interval, 813 Ventricular extrasystole, 822f Ventricular fibrillation APD restitution relationship during, 41f in Brugada syndrome, 386f detection duration of, 106-108 detection of, 79-83 from electrosurgical equipment, 1019f enhancements for, 907t ICD failure, 900f, 906-907, 906t inappropriate, 87f, 114f electrical defibrillation versus, 40 electrogram variability during, 63f mother rotor hypothesis of, 40-41 oversensing and, 72f recording of, 42f recordings/activation time for cycles after, 53f sensing of, 64 evaluation at implantation, 67 shock producing, 377f stages of, 40 underdetection of, 110f undersensing of, 66, 109, 111f ventricular electrogram during, 58 ventricular tachycardia converting to, failure of, 904-905, 905t Ventricular fibrillation detection zone, 88f Ventricular filling, 938, 940f Ventricular fusion, 355 Ventricular ICD SVT-VT discrimination in, 85-104 ventricular sensing in, 64-67 Ventricular interval, counting, 82 Ventricular intracardiac electrogram (IEGM), 870f Ventricular lead attenuation of, 867f lead dislodgment with, 483 radiography of positioning of, 781 Ventricular muscle, action potential of, 9f Ventricular oversensing, 78f, 814, 978-980 intracardiac signal and, 69-74 lead implantation and, 377 recognition/troubleshooting for, 68-79 Ventricular pacing, 64f abnormal contraction during, 206-211 algorithms to minimize, 316-318 AAIsafeR mode, 316-317 managed ventricular pacing, 316 search AV hysteresis, 316 alternative sites for, 218-219, 320 atrial fibrillation and, 314-315, 315f atrial pacing versus, meta-analysis of, 243 atrioventricular block and, 238 auxotonic relaxation and, 209 cardiac structure/function and, 211 deleterious effects of, 316f detrimental effects of, 314-318 dual-chamber pacing versus, 238-243 in defibrillator patients, 247-249 effects of, 211f, 212t on electrocardiogram, 864-865, 864f electromagnetic interference and, 1007-1008 fixed-rate versus rate-adaptive, 234 heart failure and, 239, 315-316, 315f local energetic efficiency, effect on, 207-209 mean frontal plane QRS axis during, 924f



Ventricular pacing (Continued) minimizing, 219 modes for, 317-318 to reduce AF, 317-318 MVP versus DDD(R) mode, 317f pacemaker operations minimizing, 156 pressure-volume diagrams during, 210f rate response, with versus without, 234 with rate response versus dual-chamber pacing, 234-235 rates at rest, 212f reduction of, 78-79 site-specific, in AV block, 350-353 Ventricular pacing lead in RV apex, 784f in RV outflow tract, 786f Ventricular pacing site, 156 Ventricular pacing threshold, 924 Ventricular premature beats, 973 Ventricular proarrhythmia, during LV pacing, 980-981 Ventricular rate atrial rate versus, 95 counting methods for, 82 detection zones for, 83 dual-chamber rhythm classification and, 96f stabilization leading to pacing, 842f Ventricular Rate Regularization (VRR), 972, 975f-976f BiV pacing increase during AT/AF by, 977f ventricular response pacing (VRP) and, 835 Ventricular refractory period, 813 VVI pacing and, 400f VVI pacing mode for, 814f Ventricular remodeling, 211 mechanisms of, 916f Ventricular repolarization, BiV and LV pacing effect on, 983f Ventricular response pacing (VRP), 835f ventricular rate regularization and, 835 Ventricular resynchronization, 917 Ventricular safety pacing, 78, 817-818, 819f resulting from atrial undersensing, 819f Ventricular Sense Response (VSR), 978f conducted AF response, combined effects of, 979f Ventricular sensing, in ventricular ICDs, 64-67 Ventricular septal defect (VSD), heart block and, 394 Ventricular single-chamber pacing atrial/dual-chamber pacing versus, 238-239 atrial synchronized ventricular pacing versus, 235 in sinus node disease, 237-238, 237t Ventricular synchrony maintenance of, 218 role of, 217-219 Ventricular tachycardia (VT). See also Catecholaminergic polymorphic ventricular tachycardia during AAI pacing, 319f antitachycardia pacing and, 904 detection duration before ATP, 106 detection failure for, 95f ICD system, 906-907, 906t

Index

Ventricular tachycardia (Continued) by intradevice interaction, 113f detection of, 79-83, 99f as diagnostic tool, 112-116 enhancements for, 907t inappropriate, 114f EGM morphologies of, 902 inappropriate classification of, 95 Long QT Syndrome and, 903f managed ventricular pacing causing, 352f monitor-only zones for, 83 oversensing and, 72f pacemaker diagnostics for, 112, 113f pacing-induced, 904f post-therapy sinus rhythm, detection failure, 108f during rapidly conducted atrial flutter, 100f site-specific effects of LV/RV pacing on, 982f as slower than programmed detection interval, 111, 112f undersensing and, 66, 902-904 ventricular antitachycardia pacing, atrial response to, 106f ventricular double-counting during, 981f ventricular electrogram during, 58 ventricular fibrillation, failure to convert, 904-905, 905t in ventricular fibrillation detection zone, 88f Ventricular therapy, for SVT, 104 Ventricular timing, noncompetitive atrial pacing algorithm and, 834f Ventricular triple-counting in nondedicated CRT-P system, 981f occurrence of, 978-979 Ventricular uncoupling, 911-915 Ventricular undersensing, 64f, 814 lead implantation and, 377 VVI pacing mode for, 815f Ventriculoatrial (VA) coupling, 911 Ventriculography, 229f Ventriculotomy, 768 Vert, 630f for crossing occlusion, 631f at peripheral/proximal coil, 630f without glide wire, 630f directing glide wire, 628f for crossing occlusion, 629f with no visible opening, 630f Vest Prevention of Early Sudden Death Trial (VEST), 274, 275t VF Zone High Rate Time Out, 103 Video capsule endoscopy, electromagnetic interference and, 1021 Virtual electrode cardiac excitability and, 11 description of, 11 importance of, 11 occurrence of, 11 Virtual electrode effect, 11 cause of, 376 Volt, 176 Voltage, 3 battery longevity, programming for, 35, 35f decay of, 19, 19f

1085

Voltage (Continued) for endocardial stimulation, 13 resistance and delivered capacity, relationship between, 180f Voltage-gated channel neuronal axon conduction and, 6 opening of, 6 Voltage threshold, 399-400 VOO pacing mode, 815, 836 VVI pacing, 814f diagrammatic representation of, 814f ECG tracing of demand rate of 50 bpm, 869f demand rate of 60 bpm, 869f timing cycles and, 813-815 ventricular refractory period after, 400f VVI ventricular hysteresis, 815f VVI ventricular oversensing, 814f VVI ventricular refractory period, 814f VVI ventricular undersensing, 815f VVO pacing mode, 815f VVT pacing mode, 836

W Waist, elimination of, 662f Wall integrity, loss of cardiac tamponade and, 765 treatment mechanisms for, 765 Wand-based remote monitoring, 990f Warburg impedance effect of, 22 pacing configuration of, 19f Warfarin, bolusing dosing of, 725 Waveform duration of, 43f as monophasic or biphasic, 42-45 shock strength and, 45 Wavefront block, 41-42 Waveshape, of electrogram, 57 Wedensky effect (capture hysteresis), 15 Wenckebach block, 323 Wenckebach pacemaker AV block, DDD mode upper rate response, 824f Wenckebach periodicity, 324 Wenckebach sequence, AV nodal block with, 324 Wet pocket, 480 Wire exchanging to augment support, 517, 618 Wireless cardiac simulation (WiCS) development of, 437 intracardiac electrode for, 438f pulse generator for, 438f Wireless communication device, electromagnetic interference and, 1011-1012 Wire-refractory total occlusion, 629 laser crossing of, 638 venogram of, 638f Wolff-Parkinson-White syndrome, 206, 333 Working environment, electromagnetic interference and, 1014 Wound irrigation, for infection prevention, 452-453

Z Zapper, electromagnetic interference and, 1013