Risk of arrhythmia and sudden death

Risk of Arrhythmia and Sudden Death

Edited by Marek Malik BMJ Books

Risk of Arrhythmia and Sudden Death

To my parents

Risk of Arrhythmia and Sudden Death Edited by Marek Malik Professor of Cardiac Electrophysiology St George’s Hospital Medical School, London, UK

©BMJ Books 2001 BMJ Books is an imprint of the BMJ Publishing Group

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording and/or otherwise, without the prior written permission of the publishers.

First published in 2001 by BMJ Books, BMA House, Tavistock Square, London WC1H 9JR www.bmjbooks.com British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0-7279-1581-9

Typeset by Phoenix Photosetting, Chatham, Kent Printed and bound by Creative Print and Design Ltd

Contents

Contributors Preface Abbreviations

ix xiii xv

Part I: Problem and methodology 1 Clinical goals of risk stratification Roberto Elosua, Josep Guindo, Xavier Viñolas, Antonio Martinez-Rubio, Toni Bayés-Genis and Antoni Bayés de Luna

3

2 Definition of arrhythmic risk Steen Z Abildstrom, Christian Torp-Pedersen and Lars Køber

10

3 Statistical methods for risk-stratification studies Timothy R Church

19

4 Step-wise risk-stratification strategies Stefan H Hohnloser

29

5 Risk-stratification studies for prospective trial design Marek Malik

37

Part II: Techniques of risk assessment 6 Basic clinical assessment Branco Mautner

49

7 Left ventricular ejection fraction and wall motion score Steen Z Abildstrom, Christian Torp-Pedersen and Lars Køber

57

8 Risk assessment: the 12-lead electrocardiogram Rory Childers

65

9 Electrophysiological study for risk stratification of cardiac patients Velislav Batchvarov

98

10 QT dispersion Velislav Batchvarov and Marek Malik

117

v

Risk of Arrhythmia and Sudden Death

vi

11 Electrocardiographic assessment of myocardial ischaemia (with a note on the ischaemia–arrhythmia connection) Shlomo Stern

135

12 Exercise electrocardiography for the assessment of arrhythmias Michael Cusack and Simon Redwood

144

13 Analysis of monophasic action potentials Peter Taggart and Peter Sutton

155

14 Ventricular signal averaged electrocardiography Piotr Kulakowski

167

15 Signal averaged P wave Antonio Michelucci, Luigi Padeletti, Andrea Colella, Maria Cristina Porciani, Paolo Pieragnoli, Alessandro Costoli and Gian Franco Gensini

180

16 Non-invasive investigation of Wedensky modulation Katerina Hnatkova and Marek Malik

187

17 Ambulatory electrocardiography: use in arrhythmia risk assessment Morrison Hodges and James J Bailey

194

18 Event loop recorders and implantable monitors Mark L Brown

202

19 Basic autonomic tests Federico Lombardi

209

20 Heart rate assessment and monitoring Xavier Copie, Olivier Piot, Thomas Lavergne, Louis Guize and Jean-Yves Le Heuzey

213

21 Heart rate variability Robert E Kleiger and Phyllis K Stein

221

22 Baroreflex sensitivity Maria Teresa La Rovere, Andrea Mortara and Gian Domenico Pinna

234

23 Heart rate turbulence Georg Schmidt

242

24 T wave dynamicity Pierre Maison Blanche and Philippe Coumel

249

25 Repolarisation alternans Daniel M Bloomfield and Richard J Cohen

256

26 Social and psychosocial influences on sudden cardiac death, ventricular arrhythmia and cardiac autonomic function Harry Hemingway

266

Contents

Part III: Clinical studies of risk assessment 27 Risk stratification after myocardial infarction Yee Guan Yap

287

28 Ventricular arrhythmias in chronic heart failure Steven Lindsay and Jim Nolan

297

29 Ventricular arrhythmias in hypertrophic cardiomyopathy Gang Yi and William J McKenna

309

30 Ventricular arrhythmias in apparently healthy athletes Francesco Furlanello, Fredrick Fernando, Amedeo Galassi and Annalisa Bertoldi

316

31 Paroxysmal atrial fibrillation Johan EP Waktare

325

32 Persistent atrial fibrillation Joseph T Dell’Orfano and Gerald V Naccarelli

336

33 Permanent atrial fibrillation Isabelle C Van Gelder and Harry JGM Crijns

348

34 Arrhythmias associated with the long QT syndrome Peter J Schwartz

353

35 Arrhythmia associated with other cardiac diseases Patrick Lam and Paul Schweitzer

360

36 Arrhythmias associated with non-cardiac disease Josef Kautzner

365

Part IV: Antiarrhythmic trials 37 Antiarrhythmic device trials Arthur J Moss

379

38 Recent antiarrhythmic drug trials Michiel J Janse

389

Index

395

vii

Contributors

Steen Z Abildstrom Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark James J Bailey Center for Information Technology, National Institutes of Health, Bethesda, Maryland, USA Velislav Batchvarov Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK Antoni Bayés de Luna Departamento de Cardiología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Toni Bayés-Genis Fellow, Mayo Clinic, Rochester, Minnesota, USA Annalisa Bertoldi Department of Cardiology, S. Chiara Hospital, Trento, Italy

Richard J Cohen Whitaker Professor, Harvard University–Massachusetts Institute of Technology, Division of Health Sciences and Technology, Massachusetts, USA Andrea Colella Istituto di Clinica Medica e Cardiologia, Università di Firenze, Florence, Italy Xavier Copie Department of Cardiology, Broussais Hospital, Paris, France Alessandro Costoli Istituto di Clinica Medica e Cardiologia, Università di Firenze, Florence, Italy Philippe Coumel Hôpital Lariboisière, Paris, France Harry JGM Crijns Department of Cardiology, Thoraxcenter, University Hospital Groningen, Groningen, The Netherlands

Daniel M Bloomfield Assistant Professor of Medicine, Division of Cardiology, College of Physicians and Surgeons, Columbia University, USA

Michael Cusack Clinical Research Fellow, Department of Cardiology, Rayne Institute, St Thomas’ Hospital, London, UK

Mark L Brown Staff Scientist, Tachyarrhythmia Research Department, Atrial Fibrillation Research Group, Medtronic, Minneapolis, Minnesota, USA

Joseph T Dell’Orfano Department of Medicine, Division of Cardiology, The State University of New York at Stony Brook, Stony Brook, New York, USA

Rory Childers Professor of Medicine, Section of Cardiology, University of Chicago Medical Centre, Chicago, USA

Roberto Elosua Unidad de Lípidos y Epidemiología Cardiovascular, Instituto Municipal de Investigación Médica, Barcelona, Spain

Timothy R Church Division of Environmental and Occupational Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA

Fredrick Fernando Sports Science Institute, Italian National Olympic Committee, Rome, Italy ix

Risk of Arrhythmia and Sudden Death

Francesco Furlanello S. Raffaele Scientific Institute, Milan-Rome, Italy

Piotr Kulakowski Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland

Amedeo Galassi Arrhythmia and Electrophysiological Center, S Donato Institute, Milan, Italy

Patrick Lam Beth Israel Medical Center, New York, USA

Gian Franco Gensini Istituto di Clinica Medica e Cardiologia, Università di Firenze, Florence, Italy

Maria Teresa La Rovere Fondazione “Salvatore Maugeri”, IRCCS, Divisione di Cardiologia, Centro Medico Montescano, Pavia, Italy

Louis Guize Department of Cardiology, Broussais Hospital, Paris, France

Thomas Lavergne Department of Cardiology, Broussais Hospital, Paris, France

Josep Guindo Departmento di Cardiologia, Hospital de la Santa Creui i Sant Pau, Barcelona, Spain Harry Hemingway Senior Lecturer in Epidemiology, International Centre for Health and Society, Department of Epidemiology and Public Health, University College London Medical School, London; Director of Research and Development, Department of Research and Development, Kensington & Chelsea and Westminster Health Authority, London, UK Morrison Hodges Minneapolis Heart Institute Foundation, Minnesota, USA Stefan H Hohnloser Department of Medicine, Division of Cardiology, J.W. Goethe University, Frankfurt, Germany Katerina Hnatkova Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK Michiel J Janse Cardiovascular Research, Academic Medical Center, Amsterdam, The Netherlands

Jean-Yves Le Heuzey Department of Cardiology, Broussais Hospital, Paris, France Steven Lindsay Consultant Cardiologist, Bradford Royal Infirmary, Bradford, UK Federico Lombardi Cardiologia, Dipartimento di Medicina, Chirurgia e Odontoiatria Ospedale S Paolo, Università degli Studi di Milano, Milan, Italy Pierre Maison Blanche Hôpital Lariboisière, Paris, France Marek Malik Professor of Cardiac Electrophysiology, Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK Antonio Martinez-Rubio Departamento de Cardiología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Josef Kautzner Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Branco Mautner President, International Society for Holter and NonInvasive Electrocardiology; Academic Vice-Chancellor, Favaloro University, Belgrano, Buenos Aires, Argentina

Robert E Kleiger Professor of Medicine, Washington University School of Medicine; Medical Director of Washington University School of Medicine HRV Laboratory, St Louis, USA

William J McKenna Professor of Cardiac Medicine, Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK

Lars Køber Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark

Antonio Michelucci Istituto di Clinica Medica e Cardiologia, Università di Firenze, Florence, Italy

x

Contributors

Andrea Mortara Fondazione “Salvatore Maugeri”, IRCCS, Divisione di Cardiologia, Centro Medico Montescano, Pavia, Italy

Peter J Schwartz Professor and Chairman, Department of Cardiology, Policlinico S Matteo, IRCCS and University of Pavia, Italy

Arthur J Moss Professor of Medicine (Cardiology), Director, Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, New York, USA

Paul Schweitzer Beth Israel Medical Center, New York, USA

Gerald V Naccarelli Chief, Division of Cardiology, MS Hershey Medical Center of the Pennsylvania State University, Hershey, Pennsylvania, USA Jim Nolan Consultant Cardiologist, Cardiothoracic Centre, North Staffordshire Hospital, Stoke on Trent, UK Luigi Padeletti Istituto di Clinica Medica e Cardiologia, Università di Firenze, Florence, Italy Paolo Pieragnoli Istituto di Clinica Medica e Cardiologia, Università di Firenze, Florence, Italy Gian Domenico Pinna Servizio di Bioingegneria, Fondazione “Salvatore Maugeri”, IRCCS, Centro Medico Montescano, Pavia, Italy Olivier Piot Department of Cardiology, Broussais Hospital, Paris, France

Phyllis K Stein Research Assistant Professor of Medicine, Washington University School of Medicine; Director of Washington University School of Medicine HRV Laboratory, St Louis, USA Shlomo Stern Emeritus Professor of Medicine, Hebrew University, and the Bikur Cholim Hospital, Jerusalem, Israel Peter Sutton Departments of Cardiology, UCL Hospitals and Hatter Institute, University College Hospital, London, UK Peter Taggart Departments of Cardiology, UCL Hospitals and Hatter Institute, University College Hospital, London, UK Christian Torp-Pedersen Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark Isabelle C Van Gelder Department of Cardiology, Thoraxcenter, University Hospital Groningen, Groningen, The Netherlands Xavier Viñolas Departamento de Cardiología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Maria Cristina Porciani Istituto di Clinica Medica e Cardiologia, Università di Firenze, Florence, Italy

Johan EP Waktare Cardiological Sciences, St George’s Hospital Medical School, London UK

Simon Redwood Senior Lecturer / Honorary Consultant Cardiologist, Department of Cardiology, Rayne Institute, St Thomas’ Hospital, London, UK

Yee Guan Yap Specialist Registrar in Cardiology, Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK

Georg Schmidt Deutsches Herzzentrum und Medizinische Klinik der Technischen Universität München, Munich, Germany

Gang Yi Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK

xi

Preface

In the developed world, the cost of medical care is rapidly rising and practically every clinical, pharmacological or technological breakthrough brings not only an improved quality of life and prolonged patient survival but also a significant burden on healthcare providers irrespective of whether they are privately organised or government controlled. Despite the differences in the economies and healthcare arrangements of the Western world countries, the discussions about the ever rising cost of medical care are everywhere similarly heated. Clearly, there are no easy solutions since removing a potentially life-saving treatment from any human being is not ethical. At the same time, no country of the world is so wealthy that it could afford the best available treatment and care for all its citizens. Cardiology is no exception to this trend. For instance, studies that have confirmed the efficacy and appropriateness of the prophylactic use of implantable defibrillators are examples of findings that have both clinical and financial implications. Still, compared to comprehensive safety nets and resuscitation programs designed to save patients only after they have suffered from malignant ventricular arrhythmias, prophylactic use of implantable defibrillators is most likely a cost-saving option. In general, prophylactic medicine is one of the most effective ways of reducing the overall costs of medical care while, at the same time, maintaining adequate quality of life and improving the survival of the overall population. It is therefore not surprising that prophylactic methods are presently receiving substantial attention from both clinical community and healthcare providers. The advances in prophylactic medicine are clearly dependent on improved risk markers and advanced risk stratification approaches. Again, cardiology is no exception. Cardiac risk stratification is presently being investigated not only to identify patients who might benefit from more cost-effective modes of prophylactic treatment but also, even more importantly, to save patients who would otherwise succumb to cardiac death and sudden cardiac death in particular. For all these reasons, I was very pleased when I was offered the opportunity of editing this book on risk stratification of arrhythmias and sudden cardiac death. Indeed, some of the principles and methodologies of arrhythmia

risk stratification are rather complex and, in some cases, perhaps not fully appreciated and understood by clinical cardiologists and electrophysiologists. In order to offer a comprehensive coverage of the field, I have divided the contents of the book into four sections. The first part contains chapters dealing with the general principles of risk stratification, explaining the individual facets of methodology and technology and summarising the goals of arrhythmic risk stratification studies. The second part is devoted to a detailed description of individual investigation techniques aimed at identification of patients at high risk of arrhythmia or sudden death. The third part describes the present experience with applying the risk stratification technologies and tests to patients of different clinically defined groups. Finally, the two chapters of the final part summarise the presently conducted clinical trials utilising the risk stratification techniques. As with every multi-authored book, I faced the usual editoral dilemma of finding the proper balance between having the book compact with cross-references within individual chapters and having the chapters suited for separate reading. Eventually, I felt that with a book of this size aimed at providing a source of standard references, each chapter should contain a standard coverage of its subject. Hence, I am happy to recommend the reader to select chapters corresponding to his/her particular needs and interest. Needless to say, reading the book in its entirety offers much more comprehensive learning of the whole field. Without the kind positive response of the authors of the individual chapters, this book would have never been written. I truly appreciate the efforts of the individual contributors and am very grateful for their kind help. My deep thanks also go to my secretary, Mrs Melanie Monteiro, who carefully organised the editorial office of this book and who helped me in many other ways. I am grateful to the publisher for their useful suggestions, significant technical help, and kind flexibility. My apologies go to my wife and children since far too frequently I have devoted the time that I should have spent with them to the editing of this text. Marek Malik xiii

Abbreviations

AECG AF/AT APC AT BRS CHF DAD EAD ECG EGM ERP FRP HCM HF HRV ICD ILR LF LVEF LVH MAPs MI

ambulatory electrocardiography atrial fibrillation/atrial tachycardia atrial premature contraction attributable risk baroreflex sensitivity congestive heart failure delayed after-depolarisations early after-depolarisations electrocardiograph electrogram effective refractory period functional refractory period hypertrophic cardiomyopathy high frequency heart rate variability cardioverter/defibrillator implantable loop recorder low frequency left ventricular ejection fraction left ventricular hypertrophy monophasic action potentials myocardial infarction

NPV NSVT PCA pNN50

PPV PSVT rMSSD ROC SACT SDNN SDNNIDX SNRT TO TP ULF VA VPC VT

negative predictive value non-sustained ventricular tachycardia principal component analysis percentage of normal to normal RR intervals that differ ≥50 ms from the preceding interval positive predictive value paroxysmal supraventricular tachycardia root mean square of successive differences of normal to normal RR intervals receiver-operating characteristic sinoatrial conduction time standard deviation of normal to normal RR intervals SDNN index sinus node recovery time turbulence onset total power ultralow frequency ventricular arrhythmias ventricular premature contraction ventricular tachycardia

xv

Part I Problem and methodology

1

1

Clinical goals of risk stratification Roberto Elosua, Josep Guindo, Xavier Viñolas, Antonio Martinez-Rubio, Toni Bayés-Genis and Antoni Bayés de Luna

The clinical goals of risk stratification of sudden death (SD) are to identify subjects who are at high risk and, eventually, to reduce the incidence of SD. We will focus in this chapter on aspects related to epidemiological and clinical issues to stratify risk of SD. We consider SD as a syndrome that may be associated with different diseases and situations. The term “sudden death” has been used in different ways by epidemiologists, clinicians, forensic pathologists, etc. Clinically, the term is used for deaths due to natural causes that occur within 1 hour of the onset of symptoms in a person with or without pre-existing heart disease, but in whom the time and mode of death are unexpected. In approximately one-third of cases the death is instantaneous, without symptoms or coinciding only during a few seconds with the presence of symptoms. If the patient is found dead, death is considered to be “sudden” if the subject was seen alive and well in the preceding 24 hours.1 In this chapter we shall discuss the need for identification of high-risk populations for malignant arrhythmias and sudden death. It is especially important to emphasise the paradox that the highest-risk subgroups (cardiac arrest survivors or patients with an ejection fraction