Atrial Fibrillation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

ATRIAL FIBRILLATION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES ...

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ATRIAL

FIBRILLATION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Atrial Fibrillation: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83753-8 1. Atrial Fibrillation-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on atrial fibrillation. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ATRIAL FIBRILLATION .............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Atrial Fibrillation.......................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 49 The National Library of Medicine: PubMed ................................................................................ 51 CHAPTER 2. NUTRITION AND ATRIAL FIBRILLATION..................................................................... 99 Overview...................................................................................................................................... 99 Finding Nutrition Studies on Atrial Fibrillation ........................................................................ 99 Federal Resources on Nutrition ................................................................................................. 113 Additional Web Resources ......................................................................................................... 113 CHAPTER 3. ALTERNATIVE MEDICINE AND ATRIAL FIBRILLATION ............................................ 115 Overview.................................................................................................................................... 115 National Center for Complementary and Alternative Medicine................................................ 115 Additional Web Resources ......................................................................................................... 123 General References ..................................................................................................................... 124 CHAPTER 4. DISSERTATIONS ON ATRIAL FIBRILLATION .............................................................. 125 Overview.................................................................................................................................... 125 Dissertations on Atrial Fibrillation ........................................................................................... 125 Keeping Current ........................................................................................................................ 126 CHAPTER 5. CLINICAL TRIALS AND ATRIAL FIBRILLATION ......................................................... 127 Overview.................................................................................................................................... 127 Recent Trials on Atrial Fibrillation ........................................................................................... 127 Keeping Current on Clinical Trials ........................................................................................... 130 CHAPTER 6. PATENTS ON ATRIAL FIBRILLATION ......................................................................... 133 Overview.................................................................................................................................... 133 Patents on Atrial Fibrillation..................................................................................................... 133 Patent Applications on Atrial Fibrillation................................................................................. 161 Keeping Current ........................................................................................................................ 192 CHAPTER 7. BOOKS ON ATRIAL FIBRILLATION............................................................................. 193 Overview.................................................................................................................................... 193 Book Summaries: Online Booksellers......................................................................................... 193 The National Library of Medicine Book Index ........................................................................... 195 Chapters on Atrial Fibrillation .................................................................................................. 196 CHAPTER 8. MULTIMEDIA ON ATRIAL FIBRILLATION .................................................................. 197 Overview.................................................................................................................................... 197 Bibliography: Multimedia on Atrial Fibrillation ....................................................................... 197 CHAPTER 9. PERIODICALS AND NEWS ON ATRIAL FIBRILLATION ............................................... 199 Overview.................................................................................................................................... 199 News Services and Press Releases.............................................................................................. 199 Academic Periodicals covering Atrial Fibrillation..................................................................... 203 CHAPTER 10. RESEARCHING MEDICATIONS ................................................................................. 205 Overview.................................................................................................................................... 205 U.S. Pharmacopeia..................................................................................................................... 205 Commercial Databases ............................................................................................................... 207 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 211 Overview.................................................................................................................................... 211 NIH Guidelines.......................................................................................................................... 211 NIH Databases........................................................................................................................... 213 Other Commercial Databases..................................................................................................... 216

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The Genome Project and Atrial Fibrillation .............................................................................. 216 APPENDIX B. PATIENT RESOURCES ............................................................................................... 221 Overview.................................................................................................................................... 221 Patient Guideline Sources.......................................................................................................... 221 Finding Associations.................................................................................................................. 228 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 231 Overview.................................................................................................................................... 231 Preparation................................................................................................................................. 231 Finding a Local Medical Library................................................................................................ 231 Medical Libraries in the U.S. and Canada ................................................................................. 231 ONLINE GLOSSARIES................................................................................................................ 237 Online Dictionary Directories ................................................................................................... 240 ATRIAL FIBRILLATION DICTIONARY ................................................................................. 241 INDEX .............................................................................................................................................. 301

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with atrial fibrillation is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about atrial fibrillation, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to atrial fibrillation, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on atrial fibrillation. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to atrial fibrillation, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on atrial fibrillation. The Editors

1 From

the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON ATRIAL FIBRILLATION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on atrial fibrillation.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and atrial fibrillation, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “atrial fibrillation” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Atrial Fibrillation and Its Relationship to Dental Care Source: JADA. Journal of the American Dental Association. 130(7): 1080-1085. July 1999. Summary: The number of Americans diagnosed with and treated for atrial fibrillation (AF) continues to rise. This article reports on a study undertaken to determine how AF may affect the provision of dental care. The author conducted a literature search, using terms such as 'atrial fibrillation' and 'dental care.' The author found a lack of information on these combined topics. Therefore, the author extrapolated information from articles on AF, the medical and surgical management of AF, and dental care, in order to determine appropriate guidelines for the dental treatment of patients with AF. The author found that complications can arise from AF and that medical management of AF can affect the delivery of dental care. Dentists should determine the underlying cause of AF to decide if antibiotic prophylaxis is indicated. Patients who are receiving

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anticoagulation therapy may not need to alter their therapy schedules for minor oral surgery procedures. Anxiety as a result of AF may require use of anxiety reducing protocols before dental treatment. The author concludes that the dental management of patients with AF may require treatment modifications, but generally will not deviate significantly from routine standards. 1 table. 50 references.

Federally Funded Research on Atrial Fibrillation The U.S. Government supports a variety of research studies relating to atrial fibrillation. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to atrial fibrillation. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore atrial fibrillation. The following is typical of the type of information found when searching the CRISP database for atrial fibrillation: •

Project Title: 5-D IMAGE GUIDED CARDIAC ABLATION THERAPY Principal Investigator & Institution: Robb, Richard A.; Professor of Biophysics and Computer Sci; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Cardiac arrhythmias are a major clinical problem. We propose a significant and unique solution. Based on our preliminary results and progress with minimally invasive, multi dimensional image-guided interventions for myocardial ablation of cardiac arrhythmias in experimental animals, we have developed a theoretical basis and shown significant promise for proving the hypothesis that realtime, anatomy-based imaging and accurate fusion with electrophysiologic recordings will significantly improve the outcomes of catheter-based ablation of cardiac arrhythmias. In addition to greater success with less risk of morbidity/mortality, other important benefits will include reduced procedure time, less x-ray exposure, and lower cost. Our multi-disciplinary team (biomedical engineering, cardiology, radiology, computer science) will focus on atrial fibrillation (AF) where current treatment strategies are ineffective. However, our approach and system will be adaptable to treatment of any cardiac arrhythmias that can be reached by a catheter. The target goal is to achieve outcomes with catheter-based ablation comparable to surgical procedures, which can be 80-90% effective for AF, primarily due to direct visualization of the target cardiac anatomy through the surgically opened chest. But surgical procedures are undesirably invasive and accompanied by significant risk and cost. We will test our hypothesis by developing and validating a complete prototype system for image-guided

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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catheter-based cardiac ablation featuring accurate real-time and on-line localization, visualization and targeting of the treatment region. This new system will be based on rapid volume image acquisition, real-time computer image processing and interactive display of three-dimensional anatomical images registered and mapped with electrophysiological data during successive cardiac cycles - a five-dimensional image guided intervention system. The system will be constructed using currently available microprocessors, display technology, mapping hardware and standard interfaces for 3D imaging modalities, including electron beam, CT, multirow spiral CT, MRI and ultrasound. Image processing steps, including segmentation, registration, modeling and rendering will be performed by customizing and optimizing algorithms previously developed and evaluated in our laboratory. The systems engineering task will essentially be one of designing, assembling and testing the integration of physical components (hardware, software and data) and procedural components (tasks) which have been separately developed and successfully demonstrated. This prototype system will then be thoroughly validated in the animal laboratory, with modifications and refinements for improved performance and user interface incorporated as these are indicated during the evaluation studies. We firmly believe that development, validation and optimization of this prototype system will herald a new generation of advanced technology for minimally invasive treatment of cardiac arrhythmias that will dramatically and positively impact the field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACE INHIBITION AND BETA BLOCKADE IN CONGESTIVE CARDIOMYOPATHY Principal Investigator & Institution: Katz, Arnold; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGING AND PERIOPERATIVE OUTCOMES Principal Investigator & Institution: Leung, Jacqueline M.; Anesthesia and Perioperative Care; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: (Applicant s abstract) People > 65 years of age are expected to exceed 50 million or 20% of the total population by the end of the century. The elderly undergo approximately 40% of all surgical procedures, amounting to an annual expenditure of over $60 billion. Our previous work demonstrated the postoperative in-hospital morbidity rate in octogenarians undergoing non- cardiac surgery to be 25%. By multivariate logistic regression, a history of neurological disease, congestive heart failure and arrhythmia increased the odds of developing any adverse postoperative events. Our work here focuses on the identification of the predictors of perioperative complications in geriatric surgical patients followed by clinical trials to modify the risk factor(s) in order to improve perioperative outcome. Four integrated clinical studies are planned: 1) A prospective, longitudinal cohort study of 600 consecutive geriatric surgical patients undergoing non-cardiac surgery. This study aims to determine the impact of perioperative complications on the functional status and long-term survival of the elderly surgical patients by measuring pre-defined in-hospital adverse postoperative outcomes, and functional and survival status at two years postoperatively. 2) A

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prospective cohort study of 200 geriatric patients undergoing non-cardiac surgery. This study aims to determine the accuracy of preoperative clinical methods of assessing heart function as compared to echocardiography; and also the prognostic relationship between preoperative diastolic dysfunction and postoperative heart failure. 3) A prospective cohort study of 300 patients undergoing coronary artery bypass graft surgery. This study aims to determine if left atrial dysfunction as measured by intraoperative transesophageal echocardiography provides incremental value in predicting the occurrence of postoperative atrial fibrillation when compared with routine clinical data. In later years, we will perform 4) a randomized, clinical trial of regional versus general anesthesia in 500 elderly patients undergoing orthopedic surgery. This study aims to determine the incidence of postoperative cognitive dysfunction and delirium between regional versus general anesthesia after controlling for intraoperative anesthetic and hemodynamic management and postoperative pain management. Postoperative cognitive function and delirium will be measured by standard neuropsychological tests and the Confusion Assessment Method. We believe that our studies will provide important results contributing ultimately to the improvement of perioperative outcomes in geriatric patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ATRIAL FIBRILLATION FOLLOW UP INVESTIGATION OF RHYTHM MANAGEMENT (AFFIRM) Principal Investigator & Institution: Waldo, Albert L.; Walter H. Pritchard Professor of Cardiol; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: The AFFIRM Study will compare whether optimized antiarrhythmic drug therapy administered in an attempt to maintain normal sinus rhythm has an impact on total mortality when compared to optimized therapy which merely controls the heart rate of the main pumping chambers during atrial fibrillation. The study will be analyzed on an intent-to-treat basis. The hypothesis is that in patients with atrial fibrillation, total mortality with primary therapy intended to maintain sinus rhythm is equal to total mortality with primary therapy intended to control heart rate. Because stroke is such an important endpoint, composite endpoints will include 1) total mortality and disabling stroke and disabling anoxic encephalopathy; 2) total mortality, disabling stroke, or anoxic encephalopathy, major bleeding, and cardiac arrest. A third objective is to ascertain the cost of each therapy. There are 200 sites participating in the main trial which will run from 5/96-10/99 with the goal of 5000 enrolled patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ATRIAL FIBRILLATION FOLLOW UP OF RHYTHM MANAGEMENT Principal Investigator & Institution: Kaufman, Elizabeth S.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001 Summary: The AFFIRM Study is a two-arm clinical trial of high risk patients with documented atrial fibrillation and a high risk of recurrence, morbid events, and death. The treatment will be randomized to rhythm control and anticoagulation, or rate control and anticoagulation. Consenting adults with a qualifiying episode of atrial fibrillation within 30 days and considered to be at significant risk for stroke will be categorized as single episode (in which case sinus rhythm will be restored prior to randomization) or recurrent episodes (2 or more episodes in the past 6 months). The primary endpoint of

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the trial is total morbidity. Secondary endpoints include stroke, intracranial hemorrhage, disabling anoxic encephalopathy, major non-CNS hemorrhage, cardiac arrest, cost of therapy, quality of life, and functional status. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ATRIAL FIBRILLATION IN PATIENTS AFTER CARDIAC SURGERY Principal Investigator & Institution: Funk, Marjorie; Professor; None; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ATRIAL FIBRILLATION INCIDENCE, RISK FACTORS AND GENETICS Principal Investigator & Institution: Heckbert, Susan R.; Associate Professor; Epidemiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): The goal of this research is to assess the safety of commonly used medications in relation to the risk of incident atrial fibrillation (AF), and to assess the association of several genetic polymorphisms with stroke risk after AF onset. Several lines of evidence suggest that both beta-blockers and ACE inhibitors may prevent or inhibit the atrial electrical remodeling that allows AF to become established and maintained. Withdrawal of these medications may be associated with increased risk of AF in individuals at risk. Genetic polymorphisms that promote thrombosis are associated with an increased risk of venous thrombosis, and in some studies, with arterial thrombosis including stroke or myocardial infarction. Although several recently published trials indicate that warfarin or aspirin treatment of patients with AF decreases the risk of stroke, little is known about the risk of stroke as a complication of AF in relation to genetic variants that affect clotting. The proposed project will build on successful population-based studies of myocardial infarction and stroke at Group Health Cooperative (GHC), a large non-profit health maintenance organization. Detailed information from the GHC computerized pharmacy database on the timing of medication use among approximately 1500 incident AF cases and 1750 controls with medically treated hypertension will permit us to assess the risk of incident AF associated with the use or recent stopping of beta-blockers or ACE inhibitors. This project will collect DNA samples on a population-based inception cohort of approximately 855 AF patients, and will examine the risk of stroke in relation to genetic variants known to affect coagulation. The main tasks of the proposed project are: 1) identification of cases with incident AF and controls; 2) review of outpatient and inpatient medical records to assess eligibility and collect information on risk factors and medical history; 3) classification of medication use over time; 4) for AF patients, telephone interview and collection of blood samples; 5) blood specimen processing, DNA extraction, and genotyping; and 6) data analysis of the associations of medication use and genotype with AF onset and stroke complications. This project will contribute important information about drug safety and will incorporate advances in molecular biology to study AF and its complications, problems of considerable public health importance in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ATRIAL FIBRILLATION: ANATOMY VERSUS CELL PHYSIOLOGY Principal Investigator & Institution: Hastings, Harold M.; Professor; Physics; Hofstra University 210 Weller Hall Hempstead, Ny 11550 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Chronic atrial fibrillation, affecting more than 2 million patients in the US and causing 15 percent of all strokes, currently presents one of the greatest treatment challenges in cardiac electrophysiology. Atrial fibrillation is accompanied by both clinically apparent alterations in overall atrial anatomy such as pronounced dilatation, and experimentally measurable changes in tissue and cellular electrophysiology including changes in conduction velocity and restitution properties. The combination of anatomic and electrophysiologic abnormalities has been suggested as a reason that atrial fibrillation occurs and is perpetuated. It is our hypothesis that the anatomical structure of diseased atria is the dominant factor in allowing normally selfterminating atrial fibrillation to become sustained, while cellular electrophysiology plays a more limited role. To test this hypothesis, we will develop computer models of both normal and diseased atrial structure and cell physiology and simulate atrial fibrillation to determine whether diseased anatomy, remodeled electrophysiology, or both are necessary to support sustained atrial fibrillation. This research should lead to future animal experiments and ultimately clinical applications. If altered anatomy is indeed a primary mechanism that allows atrial fibrillation to become sustained, the anticipated clinical relevance to treatments such as radiofrequency catheter ablation is significant, in that it may be possible to develop more effective ablation patterns by taking into account the anatomical details of individual patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ATRIAL FIBRILLATION: MECHANISMS AND PREVENTION Principal Investigator & Institution: Rosen, Michael R.; Gustavus A. Pfeiffer Professor of Pharma; Pharmacology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-JUL-2004 Summary: (the applicant's description verbatim): Atrial fibrillation is a major cause of morbidity as well as of mortality due to stroke in the United States. Moreover, atrial fibrillation - once it occurs- tends to recur and to become persistent, such that most clinical interventions used remain palliative rather than curative. The goal of the proposed studies is to consider the mechanisms for the initiation of atrial fibrillation in a way that stresses early warnings of the likelihood of fibrillation and modalities for prevention. As such, we rely on the ECG and vectorcardiogram to study the P and Ta waves and the effects on these of altered atrial rate and activation, as the heart is paced at various rates and at various sites in a conscious canine model. We also consider the remodeling that occurs electrophysiologically with alterations in activation and rate in studies of intact animal and cellular electrophysiology, ion channels and gap junctions. We then proceed to the induction of atrial fibrillation, observing its evolution from non-sustained to sustained and the association of P and Ta wave changes, cellular electrophysiology, ion channels and gap junctions that occur with this sequence. Finally, in considering new modalities of prevention we use individual and combined approaches with an antiarrhythmic drug, an angiotensin II receptor-blocking drug and a Ca channel agonist to attempt to slow and/or reverse evolution of the substrate. Among the variables intensively studied are the rate-related changes in action potential characteristics in multicellular preparations, the role of Ca in determining these events, changes in inward (Na and Ca) and outward (K) currents that contribute to cardiac

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repolarization and the molecular determinants of gap junctional function. Finally, because of the role of age as an independent risk factor in the clinical expression of atrial fibrillation, and our preliminary data suggesting significant alterations in repolarizing currents with age, all studies are performed in adult and old animals. The significance of the work is in the attempt to utilize an understanding of mechanism in the design of methods for early identification of risk, and in the testing of modalities for prevention in an adult population and an aged population. Although cellular electrophysiologic and biophysical and molecular biological techniques are used the approach is not reductionist, but integrative, deliberately focused on synthesizing a mechanistic understanding of clinically-observed changes in P and Ta waves and their utilization in prediction and prevention of atrial fibrillation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BENEFICIAL EFFECTS OF SINUS RHYTHM ON HEMODYNAMIC PARAMETERS Principal Investigator & Institution: Silverman, David; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CA2+-MEDIATED MECHANISMS OF ATRIAL PACEMAKER ACTIVITY Principal Investigator & Institution: Lipsius, Stephen L.; Physiology; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (adapted from the applicant's description): The long-range goal of the applicant is to understand the physiological mechanisms that determine and regulate atrial pacemaker activity, particularly with respect to latent atrial pacemakers and their contribution to atrial dysfunction. Latent atrial pacemakers are specialized cells localized in specific regions of the right atrium outside of the SA node region. They are thought to participate in a wide variety of atrial arrhythmias including brady-tachy syndrome, atrial tachycardia, supraventricular tachycardia and atrial fibrillation. Although of major clinical importance, the cellular mechanisms underlying latent atrial pacemaker activity are not well understood. Preliminary results by the applicant indicate that latent atrial pacemaker activity is regulated by bursting of local intracellular Ca2+ release, i.e., Ca2+ sparks, from the sarcoplasmic reticulum (SR) specifically during the late phase of diastolic depolarization. The mechanisms governing diastolic release of SR Ca2+ in atrial pacemaker cells is not clear. Whole-cell (perforated & ruptured patch) recording methods and measurements of intracellular Ca2+ concentration ((Ca)i) using laser scanning confocal microscopy will be used to determine the mechanism governing diastolic SR Ca2+ release in latent atrial and SA node pacemaker cells isolated from cat right atrium. The following hypotheses will be tested: 1) voltage-dependent activation of T-type Ca2+ current (ICa,T) during the late diastolic slope triggers SR Ca2+ release which in turn stimulates inward Na/Ca exchange current to depolarize the membrane to threshold, 2) both acetylcholine and norepinephrine regulate diastolic SR Ca2+ release triggered by ICa,T and thereby regulate atrial pacemaker activity, 3) by elevating (Ca)i, cardiac glycosides and low extracellular (K) enhance this normal mechanism of atrial pacemaker automaticity, and thereby elicit

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atrial dysrhythmias not dependent on Ca2+ overload of the SR, 4) low temperature inhibits atrial pacemaker activity by inhibiting diastolic SR Ca2+ release triggered by ICa,T, and 4) transitional atrial pacemaker cells lack diastolic time-dependent currents and therefore depend primarily on SR Ca2+ release triggered by ICa,T for their pacemaker mechanism. It is expected that the results gained from these studies will provide fundamental insight into the cellular mechanisms governing normal and abnormal atrial pacemaker function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIAC NA-CA EXCHANGER: HYPERTROPHIC REGULATION Principal Investigator & Institution: Menick, Donald R.; Professor; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The etiologies of late hypertrophy and heart failure are extremely complex but altered cellular calcium regulation appears to be a final common cause in both arrhythmogenesis and contractile dysfunction. The SR Ca2+-ATPase (SERCA) and sarcolemmal Na+-Ca2+ exchanger (NCX1) are two major transporters responsible for reducing [Ca2+]i to a low resting level during relaxation. SERCA expression and activity are decreased in hypertrophy and failure and we and others have shown that expression and activity in NCX1 is increased in this situation. Recent reports have demonstrated that upregulation of the exchanger appears to be a critical link between contractile dysfunction and arrhythmogenesis. Additional studies have documented the cardioprotective effect resulting from inhibition of calcium influx via NCX1 in ischemia/reperfusion, digitalis toxicity and atrial fibrillation-induced shortening of atrial refractiveness. So far these results are solely based on acute studies and do not address long-term treatment. We discovered that inhibition of NCX1 calcium influx pathway (reverse mode) either by KB-R7943 or by lowering [Ca2+]o, resulted in the activation of signaling factors that leads to specific upregulation of the exchanger gene. This novel and exciting finding should have a profound impact on potential long-term treatment and places regulation of exchanger activity in a whole new light. The exchanger, whose activity is acutely sensitive to [Ca2+]o, [Ca2+]i, [Na+]i, and membrane potential (Em), may also act as a cellular rheostat that plays a role in the modulation of specific signal transduction pathways. Our hypothesis is that alteration of exchanger activity can directly activate signal transduction pathways resulting in changes in exchanger gene expression. This will be tested through the following aims: 1) Determine that the KBR induced activation of p38 and upregulation of NCX1 is directly mediated by the exchanger. 2) Determine whether changes in exchanger activity transduce the activation of signaling pathways by direct interaction or via changes in [Ca2+]i. 3) Identify factors interacting directly with the exchanger that mediate the activation of p38. 4) Identify the downstream factors in the signaling pathway mediating p38 activation. This work will allow us to better understand the role that exchanger activity plays in failure and provide a framework for therapeutic development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPUTER-GUIDED FIBRILLATION

DESIGNER

ABLATION

OF

ATRIAL

Principal Investigator & Institution: Cherry, Elizabeth M.; Physics; Hofstra University 210 Weller Hall Hempstead, Ny 11550 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005

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Summary: (provided by applicant): Catheter ablation techniques to treat chronic reentrant atrial fibrillation (AF) have been largely unsuccessful. We postulate that a major determinant of failure is the extreme variability in atrial structure among patients, so that no single catheter ablation strategy will be successful; rather, therapy must be individualized for a given patient. We hypothesize that incorporating specific anatomic information about an individual patient's atrial structure into the ablation strategy will increase the likelihood of success. In this project, we propose to perform the fundamental research necessary to bring patient-specific ablation therapy to the animal laboratory and, ultimately, to human patients. Using three-dimensional endocardial mapping techniques during electrophysiologic diagnostic studies, patient-specific atrial anatomy will be reconstructed from data sets containing the locations and electrogram characteristics of atrial points obtained by a catheter probe. Simulations of AF will be performed using the reconstructed atria. Within this framework, different ablation strategies will be tested in silico to determine how ablation lesions can be successfully performed for each specific individual anatomic structure. This work is designed to lead directly to testable ablation strategies and to novel clinical paradigms in the treatment of AF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--AMBULATORY ELECTROCARDIOGRAMS Principal Investigator & Institution: Stone, Peter H.; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001 Summary: The main responsibility for the Ambulatory ECG Core is to provide analytical support for other projects which are designed to assess the impact of air pollution on vulnerability to cardiac arrhythmias. The ECG will be assessed both in terms of conventional endpoints including heart rhythm and ST-segment and QRST morphology, and for autonomic tone and cardiac vulnerability. The latter will be determined using the spectral analytical techniques of heart rate variability (HRV) and T-wave alternans, respectively. In the case of Project #1, the analyses will be directed to measuring the effects of air pollution on patients with documented myocardial infarction initially, and for subsequent groups as required. For Project 2, the Core will be a resource of expertise in cardiology. For Project 3, the analyses will provide information concerning the effect of air pollution on the free-living elderly. HRV provides a measure of autonomic balance, an important factor influencing cardiac vulnerability and a possible mediator of the deleterious influences of air pollution. T-wave alternans is a beat-by-beat variation in the area and morphology of that waveform and has been shown in numerous experimental studies to be predictive of ventricular fibrillation during diverse physiologic and pharmacologic interventions. HRV and T- wave alternans have been shown in clinical investigations to be valuable in risk stratification in diverse forms of cardiac disease. Ambulatory BCO data will be analyzed with a high capacity, state-of-the-art MARS Unity Workstation, which runs validated software for all of the standard ECG endpoints and for HRV analysis in time and frequency domains. We have recently developed and validated the software for complex demodulation of the T-wave to quantify the level of alternans and have employed the method in records of ambulatory patients with angina and silent ischemia. Thus, with the availability of this system and the involvement of individuals who are highly experienced in its use, it will -be possible to process and analyze sizeable numbers of ECG data which will be generated by Projects l & 3. Ultimately, this comprehensive hypothesis- directed approach to ECG analysis should provide important insights regarding the effects of air

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Atrial Fibrillation

pollution on cardiac vulnerability and should help to elucidate the underlying mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MICROARRAY SUPPORT Principal Investigator & Institution: Levy, Shawn E.; Research Assistant Professor and Directo; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Vanderbilt University has established a state-of-theart microarray facility that is presently supported by the Vanderbilt-Ingram Cancer Center, the Diabetes Center and the Vanderbilt NIDDK Biotechnology Center. This facility provides high quality microarray production, hybridization and data analysis for members of these research centers. Core B will enable Program investigators access to the full spectrum of advanced technologies offered by this resource. Projects 0010, 0011 and 0013 will utilize Core B for proposed experiments aimed at revealing changes in gene expression associated with arrhythmia susceptibility. In Project 0010, experiments have been outlined to compare gene expression patterns between mice expressing a CaM Kinase II inhibitory peptide or control peptide in heart in experimental cardiomyopathies. These experiments seek knowledge of the role of CaMKII and its upstream and downstream regulators on molecular pathways leading to cardiac failure and arrhythmias. Project 0011 will utilize microarray experiments to study an in vitro cell culture system for examining electrical remodeling in atrial myocytes subjected to rapid pacing, with the goal of identifying early molecular changes contributing to an atrial fibrillation-susceptible phenotype. Project 0013 has developed a novel molecular resource, a canine expressed sequence tag (EST) collection from heart, that will be used to develop gene arrays to be applied initially to dog models of susceptibility to arrhythmias closely resembling human disease. Core B consists of two main critical elements: (1) microarray production and hybridization; and (2) data acquisition and analysis. Both elements operate with state-of-the-art technological and computational tools that guarantee superior quality and reliability in microarray experiments. The Core will support the salaries of key personnel needed for operating the core, equipment and other infrastructure costs that enable expansion of existing services, and support for expertise in analysis of the data that emerge from microarray experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DATA COORDINATING CENTER FOR PACING MODE SELECTION TRIAL Principal Investigator & Institution: Lee, Kerry L.; Associate Professor of Biostatistics; Community and Family Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-JUN-1995; Project End 31-MAY-2001 Summary: The objective of this proposal is to establish a Statistical and Data Coordinating Center for the multicenter pacemaker Mode Selection Trial (MOST) in patients with sick sinus syndrome. The study is a two-arm, single blind, randomized clinical trial that will enroll 2,000 patients who require permanent pacemaker implantation. Qualifying patients will receive a dual chamber pacemaker, which prior to implantation, will be noninvasively programmed by random assignment to either single chamber ventricular pacing (VVIR) or dual chamber, rate-modulated pacing (DDDR). Following discharge, all patients will be followed via clinic visits at 1, 3, and 6 months, and at 6-month intervals thereafter. Patients will be recruited into the trial over a period

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of 3 years, with a subsequent minimum follow-up period of 1.5 years. The primary endpoint of the trial is a composite outcome consisting of all-cause mortality or nonfatal stroke. Important secondary endpoints include (1) quality of life and cost effectiveness, (2) total mortality, (3) cardiovascular mortality, (4) death, stroke, or congestive heart failure requiring hospitalization, (5) atrial fibrillation, (6) heart failure score, and (7) pacemaker syndrome. In collaboration with the Clinical Coordinating Center and the Quality of Life and Cost Center, the Data Coordinating Center will perform the following major functions: (1) participate in all phases of planning and study design; (2) coordinate the preparation of data collection forms and procedures; (3) prepare a manual of operations; (4) provide training and guidance in data collection procedures; (5) coordinate the randomization of patients; (6) efficiently organize the flow and management of all patient data; (7) establish and adhere to high standards of quality control for data management; (8) perform on-site monitoring of completed data forms; (9) prepare weekly status reports for the Clinical Coordinating Center and Quality of Life and Cost Center; (10) prepare regular reports for study committees; (11) coordinate and perform appropriate statistical analyses of study data; and (12) participate in the preparation of study publications. Noteworthy features of this proposal include: a detailed assessment of sample size requirements; telephone randomization of patients; double data entry; complete follow-up of all patients; on-site audits of data by trained nurse monitors; use of economical and efficient computer hardware and software; stateof-the-art methods of data analysis; and an experienced team of investigators. Through the services it provides, which extend across all aspects of study design, data collection, data management, and data analysis, the Data Coordinating Center will be a vital resource in the execution of this clinical trial. The results of this study are anticipated to provide important new clinical information and to greatly enhance the appropriateness of pacemaker therapy in patients with sick sinus syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIASTOLIC DYSFUNCTION & ATRIAL FIBRILLATION IN ELDERLY Principal Investigator & Institution: Tsang, Teresa S.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Nonvalvular atrial fibrillation (AF) is an agerelated public health problem associated with marked morbidity and mortality. We propose to prospectively examine the structural, hemodynamic, and neurohormonal/ inflammatory factors associated with first AF and investigate whether sleep apnea independently predicts AF. In Aim 1, we will confirm that diastolic function and left atrial (LA) volume are predictive of AF, incremental to clinical and other echocardiographic variables. We hypothesize that diastolic dysfunction and increased LA volume independently predict nonvalvular AF. In Aim 2, the distribution and correlates of changes in diastolic function and LA volume will be described, and we will determine whether serial measurements of these parameters provide incremental information on risk of AF. In Aim 3, we plan to explore how neurohormonal activation, specifically atrial natriuretic peptide (ANP) release, and the inflammatory marker, Creactive protein (CRP), are associated with LA size, diastolic function, and AF development. We hypothesize that there is an independent role for ANP, but not for CRP, in the prediction of AF, after clinical and echocardiographic parameters have been considered. In Aim 4, we will assess relationships between arterial stiffness, diastolic function and LA volume, and determine whether arterial stiffness independently

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Atrial Fibrillation

predicts AF. In Aim 5, we will evaluate sleep apnea as an independent predictor of AF development, after accounting for other clinical and echocardiographic risk factors. We plan to recruit 800 adults at significant risk for nonvalvular AF on the basis of age > 65 years and the presence of two or more known AF risk factors (hypertension, diabetes, history of coronary artery disease, and history of congestive heart failure). Prior history of AF, embolic stroke, organic valvular disease and congenital heart disease are the major exclusion criteria. All participants must be able to provide informed consent. Echocardiography, electrocardiogram (ECG), ANP, CRP, noninvasive arterial stiffness assessments (pulse wave velocity and augmentation index) will be obtained at baseline and annually thereafter. The Berlin Sleep Questionnaire to assess risk of sleep apnea will be completed by all participants at baseline and annually. A subgroup of 200 participants will undergo sleep studies, using a portable recording system, for detection of sleep apnea. Ascertainment of AF involves regular ECG surveillance, and patient report of AF with ECG confirmation. Identification of the cascade of factors contributing to AF development will have important implications in primary prevention of this major public health problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOES VT BEGET VT? REMODELING IN HEALED INFARCTION Principal Investigator & Institution: Callans, David; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Protracted atrial fibrillation (AF) conditions the atrium through electrical remodeling to perpetuate AF (AF begets AF). Whether this is true for episodic ventricular tachycardia (VT) due to healed myocardial infarction (MI) is not known so this proposal asks whether VT begets VT. A related issue is how VT electrically remodels the infarcted ventricle. Experimental and clinical evidence indicates that postNG VT is reentrant. While VT maintenance mechanisms are controversial, the role of refractoriness in VT initiation is usually not disputed. We therefore propose to study whether episodic VT affects VT inducibility and remodels refractoriness. Study hypotheses were based on the distinct properties of the infarcted (1Z), border (13Z), and normal (NZ) zone tissues associated with MI and on the phenomena of repolarization remodeling due to cardiac memory, failure or hypertrophy. Hypothesis 1 is that VT remodels refractoriness even in hearts already remodeled by MI. Hypothesis 2 is that refractoriness remodeling in the IZ, BZ and NZ differentially responds to the influence of VT rate versus site of origin. Hypothesis 3 is that VT-dependent changes in inducibility result from differences in refractoriness remodeling of the BZ with respect to the IZ or to the NZ. Hypothesis 4 is that changes in BZ and NZ plateau and repolarization currents are responsible for refractoriness remodeling in these tissues. To test these hypotheses we will use swine having healed MI caused by bead embolization. Fast or slow ventricular pacing (VP) from 1 of 3 test sites will simulate episodic VT. VT inducibility and peri-infarct endocardial refractoriness; will be assessed in vivo using CARTO electro-anatomic catheter mapping before and after MI and after VP of MI. Terminal in vitro studies will use whole cell voltage clamp to correlate remodeled BZ and NZ refractoriness with changes in plateau ion currents. We will measure steady state, peak activated and kinetic properties of Ik and ICaL and the current-voltage relations of Ik1 and InaCa. Indo-1 and fluo-3 recordings of the calcium transient will be used to determine the direction and relative magnitude of InaCa flux. Refractoriness due to INa reactivation will be detected via voltage and time-dependent recovery of upstroke velocity. If the study hypotheses are true then the labile and inhomogeneous

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remodeling properties of the post-MI heart may cause episodic VT to have either a positive or negative effect on VT inducibility. If the latter occurs then novel therapy based on pacing may be possible. If the former is true then preventive therapy could be directed against such remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTRODE DESIGN FOR CARDIAC TACHYARRYTHMIA RF ABLATION Principal Investigator & Institution: Webster, John G.; Professor; Biomedical Engineering; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 30-JUN-2003 Summary: (Adapted from Applicant's Abstract): The goal of this study is to optimize catheter design for the cure of atrial fibrillation and ventricular tachycardia by endocardial radiofrequency (RF) ablation. It is estimated that currently in the USA about 2 million people are affected by some form of atrial fibrillation. Also, each year about 200,000 patients are treated for ventricular tachycardia. Atrial fibrillation, although itself not fatal, is a frequent cause of stroke and is linked to a high degree of cardiovascular mortality. Ventricular tachycardia is the main cause of sudden cardiac death, affecting particularly patients suffering from myocardial infarction. To cure cardiac dysrhythmias, radiofrequency current flows through an electrode on a catheter in contact with the endocardium to ablate undesired arrhythmia substrates. This research will improve the electrodes and improve the procedure. In vitro tests on myocardium will yield physical parameters of electric conductivity, and thermal conduction, capacity, and heat convection variation throughout the endocardium. In vivo swine tests will improve accuracy of most parameters. The parameters will be used to improve a 3-dimensional finite element computer model that simulates the electric power deposited, the myocardial temperature rise and the volume and distribution of the 50 degree Celsius contour that defines the lesion boundary. Further in vitro and in vivo tests will confirm the accuracy of the model. The model will predict lesion volumes resulting from proposed new electrodes. These are (1) uniform current density electrodes that prevent hot spots, steam generation "popping" and coagulum formation; (2) noncontact electrodes that generate larger lesions; (3) needle electrodes that generate larger lesions; (4) long electrodes that generate linear lesions for curing atrial fibrillation; (5) balloon electrodes that permit large imprints; (6) cooled electrodes; and (7) other novel electrodes. The model will aid in the design of new electrodes. The model will also predict the lesion volume at each ablation site. These volume predictions will form guidelines for setting tip temperature to achieve desired lesion volume at each ablation site and thus enhance present ablation techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ELECTROPHYSIOLOGY MYOCARDIUM IN AF

OF

THE

PULMONARY

VEIN

Principal Investigator & Institution: Olgin, Jeffrey E.; Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Atrial fibrillation is the most common arrhythmia and accounts for significant morbidity and mortality. Recently, evidence has suggested that atrial fibrillation may be a result of focal activity from the atrial myocardium of the pulmonary veins. However, the mechanism of this form of atrial fibrillation is not

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Atrial Fibrillation

known nor is the reason why there is a predominance of these foci in the pulmonary veins. It is the long-term goal of this application to study the electrophysiologic properties of the atrial myocardium of the pulmonary veins and define structure/function relationships of the arrhythmogenic substrate. In particular, we will utilize high resolution optical mapping of cardiac activation in a canine model of atrial dilatation and atrial fibrillation to identify the precise mechanism of focal atrial fibrillation. In the first Specific Aim, we will identify the potential substrate for arrhythmias in the myocardium of the pulmonary vein and identify the role of triggers such as calcium channel agonists and a-adrenergic agonists. In the second Specific Aim, we will study the role of acute pulmonary vein dilatation on the substrate and triggering of focal atrial fibrillation. In the third Specific Aim, we will study the effect chronic pulmonary vein dilatation on the substrate and mechanism of focal atrial fibrillation. In the last Specific Aim, we will study how focal discharges from the pulmonary vein myocardium interact with the vulnerable substrate of the remainder of the atrium to produce sustained atrial fibrillation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY FIBRILLATION

OF

ANTICOAGULATION

IN

ATRIAL

Principal Investigator & Institution: Singer, Daniel E.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-MAR-2006 Summary: We propose to continue our studies of a uniquely informative cohort of greater than 13,559 patients with atrial fibrillation (AF) from Kaiser Medical Care Program of Northern California ("Kaiser"). Our overall goal remains to optimize prevention of stroke in AF by improving selection of patients treated with anticoagulants, and by improving the management of anticoagulation. AF is the most common significant cardiac rhythm disorder. Its frequency increases strikingly with age, reaching a prevalence of nearly 10 percent in those over age 80. AF is also a powerful risk factor for stroke, raising this risk 5-fold. Randomized trials (RCTs) have established that anticoagulation largely removes the stroke risk posed by AF. Nonetheless, warfarin remains a burdensome and risky therapy. There is considerable uncertainty whether warfarin therapy will prove beneficial under real-world conditions. Guidelines call for long-term anticoagulation, and for use of anticoagulants in the elderly. Yet, the RCTs were relatively brief, with a mean follow-up of only 18 months, and few patients greater than or equal to 80 years old were studied. During the 2.7 years of current funding we have established methods to assemble a very large AF cohort, characterize baseline features and warfarin status, and follow for thromboembolic and hemorrhagic events. This has been accomplished efficiently via comprehensive automated clinical and administrative Kaiser databases supplemented by medical chart review. Continued follow-up of our AF cohort will provide unique assessments of both the long-term impact of anticoagulation and the impact of anticoagulation among the oldest patients with AF. Further, we will be able to address other important controversies including the need for anticoagulation in patients greater than or equal to 65 years old without other risk factors for stroke, and the optimal intensity of anticoagulation in older AF patients. In addition, we will address the provocative new finding that estrogen replacement therapy substantially raises the risk of stroke among women with AF. In all, continued study of our cohort will efficiently provide powerful insights into optimizing stroke prevention strategies for the many older Americans with AF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FEASIBILITY STUDY PAROXYSMAL ATRIAL FIBRILLATION

OF

CATHETER

Principal Investigator & Institution: Haines, David; Charlottesville Box 400195 Charlottesville, Va 22904

ABLATION

University

of

17

FOR

Virginia

Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOCAL MODIFICATION OF ELECTRICAL CONDUCTION IN THE HEART Principal Investigator & Institution: Donahue, John K.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 30-NOV-2006 Summary: (provided by applicant): Conventional approaches for the treatment of cardiac arrhythmias are limited to pharmacotherapy, ablation or implantable devices. Each of these strategies is effective in certain situations, but each is also associated with a number of untoward effects. With the limitations of currently available therapies, there is a need for new approaches to treat common cardiac arrhythmias. The central hypothesis of this proposal is that genetic manipulation of the cardiac substrate in a controlled, localized manner can effectively treat cardiac arrhythmias. As an initial attempt to investigate this theory, we will focus on the atrioventricular node, an anatomically well-defined region where functional changes are easily observed. Realizing the limitations of prior in vivo gene transfer strategies, this proposal seeks to investigate the central hypothesis in a systematic fashion by defining the variables important for vector delivery, by limiting the area of investigation to a specific intracardiac region, and by using conventional cellular techniques to investigate the mechanisms responsible for the observed phenotypic changes. To that end, the overall goal of this proposal will be to suppress AV nodal conduction in a controllable manner, sufficient to reduce the heart rate during atrial fibrillation but not to produce complete AV block. The specific aims to be addressed include: 1) To evaluate the effect of manipulating basic physiological variables on the efficiency of in vivo gene delivery to the AV node. 2) To evaluate the effect on AV nodal conduction of gene transfer-induced alterations in cellular levels of G proteins and potassium channels, and 3) To characterize the cellular mechanisms responsible for suppression of AV nodal conduction in states of gene transfer-induced protein overexpression. Successful completion of these aims will provide proof of principle that gene therapy strategies are viable options for the future treatment of common cardiac arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FRAMINGHAM OFFSPRING STUDY: PSYCHOSOCIAL RISK FACTORS Principal Investigator & Institution: Eaker, Elaine D.; Eaker Epidemiology Enterprises, Llc 8975 County Rd, V Chili, Wi 54420 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2003 Summary: (Provided by Applicant) The outstanding design and methods of the Framingham Offspring Study offers the next major step in understanding how behavioral, psychological, and social factors not only contribute to health and illness, but also interact with biological factors to influence health outcomes. A unique data set

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Atrial Fibrillation

of social, psychological, and behavioral measures were collected at the third examination of the Offspring Study from 1984 through 1987 (which results in 14 to 17 years of follow-up). Hypotheses for this research are focused toward understanding the sex and age differences in the effects these variables have on health endpoints. The research questions involve the prediction of three separate endpoints: incidence of coronary heart disease; the incidence and prognosis of atrial fibrillation; and total mortality. The analyses of psychosocial predictors for these outcomes are divided into four conceptual areas: 1) occupational status and strain, income, and employment status; 2) type A behavior, expressions of anger, hostility, and rate; 3) symptoms of depression, tension, anxiety, and feelings of aloneness; and 4) marital relationships and marital strain. These psychosocial variables will be analyzed jointly with the physiological risk factors collected at the same time to assess independence and interaction of effects. To date these psychosocial data have not been analyzed or published. There are many studies that have examined the associations between psychological and social characteristics and cardiovascular morbidity and mortality. Findings from these studies, however, are often conflicting and may result from inadequate study designs (e.g., case-control where psychosocial assessment takes place after the health event of interest), use of different measures or scales, study of noncomparable populations, or defining different outcomes. The strength of the Framingham Study involves longitudinal data collection; large numbers of both men and women; a standard and thorough follow-up protocol; careful assessment of heart disease and mortality endpoints; collection of information on other risk factors for disease and death concurrently with psychosocial risk factors (enabling the examination of and control for confounding or causal pathways); and the ability to examine the interrelationships between a number of different psychosocial risk factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC BASIS OF ATRIAL FIBRILLATION Principal Investigator & Institution: Ellinor, Patrick T.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 30-NOV-2007 Summary: (provided by the applicant): The candidate has a basic science background in cellular physiology and has recently completed medical residency, cardiology and electrophysiology fellowship training. He is currently a clinical research fellow and will join the staff of the Cardiology Division at Massachusetts General Hospital in July 2002. The candidate seeks to obtain formal training in clinical research methods while developing a research program to elucidate the molecular basis of atrial fibrillation. Atrial fibrillation is the most common significant arrhythmia, affecting over 2 million Americans. Although rare in youth, the prevalence of atrial fibrillation increases with age and afflicts one in ten individuals over eighty. Atrial fibrillation presents a considerable socioeconomic burden, associated with chronic medication use, nearly one fourth of all strokes in the elderly, and a reduced life expectancy in affected individuals. Most atrial fibrillation is considered secondary to other conditions such as hyperthyroidism, hypertension, cardiomyopathy or valvular disorder; however, a substantial minority of patients without obvious cause are said to have "!one" atrial fibrillation. The clinical heterogeneity of atrial fibrillation has restricted previous attempts to define the genetic etiology of this disorder. We therefore propose use of a complementary strategy of individuals and families to further define the clinical phenotypes, the genetic epidemiology, and the genetic basis of this disorder. Of patients with atrial fibrillation, we hypothesize that individuals with lone atrial fibrillation are

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the most likely to have a genetic component to their condition. We propose to prospectively study these individuals and their first-degree relatives in order to formally define the genetic architecture of atrial fibrillation while identifying larger kindreds suitable for positional cloning approaches. With this approach, we have characterized over one hundred probands with lone atrial fibrillation and identified multiple extended families with inherited atrial fibrillation. Further efforts to identify the causal genes are underway. Identification of these genes will permit definition of the molecular pathways that contribute to atrial fibrillation, while the availability of the probands will enable longitudinal studies using genotypes to predict outcomes and enable detailed evaluation of gene-gene and gene-drug interactions. The ultimate goal of these complementary strategies is to lead to novel therapeutic strategies for the prevention and treatment of this common and morbid condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC DETERMINANTS OF HEMATOMA VOLUME Principal Investigator & Institution: Rosand, Jonathan; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Intracerebral hemorrhage (ICH), bleeding into brain parenchyma from an arterial source, is the deadliest form of stroke and, in contrast to ischemic stroke, lacks any well-proved effective therapy. Although the majority of cases of ICH are spontaneous, ICH is also the most feared complication of warfarin, a medication indicated for long-term use in millions of Americans with atrial fibrillation. When associated with warfarin, ICH is even more devastating, with fatality over 50%. This research program aims to identify the genetic predictors of outcome from ICH and from ICH specifically related to warfarin. It will investigate apolipoprotein E genotype (APOE) and the factor XIII Val34Leu polymorphism. The objectives of this proposal are to determine 1) whether APOE predicts large hematoma volume in acute ICK, acute hematoma enlargement, and poor clinical outcome from acute ICH, and 2) whether factor XIII Val34Leu predicts hemorrhage recurrence in survivors of ICH, and is an independent protective factor for outcome from ICH related to warfarin. These objectives will be completed in a carefully characterized cohort of consecutive cases of spontaneous ICH. Because of the rapid growth in the understanding of both the human genome and the molecular basis of coagulation and vessel pathology, this cohort is likely to form the foundation of a powerful, open-ended search for genetic determinants of ICH and serve as a crucial tool for future studies. During the award period, in addition to serving as principal investigator for the proposed studies, Dr. Rosand will complete formal didactic training in research ethics, epidemiology, and biostatistics with a focus on the statistics applied to genetic studies of complex diseases. His mentor will be Dr. Steven M. Greenberg. Drs. James F. Gusella and Walter J. Koroshetz will serve as co-mentors. Upon conclusion of the award, Dr. Rosand, who has completed clinical fellowship training in stroke and critical care neurology, will have acquired the requisite skills to function as an independent investigator with specific expertise in genetic epidemiology. He will be trained to conduct fundamental studies in clinical and molecular epidemiology of acute cerebrovascular disease as well as pivotal clinical trials of novel therapeutic interventions for ICH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Atrial Fibrillation

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Project Title: GENETIC MARKERS OF THROMBOSIS IN EMBOLIC STROKE Principal Investigator & Institution: Furie, Karen L.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Approximately 60% of all ischemic strokes are believed to be due to emboli. It is well established that the risk of embolic stroke increases with age. Although certain underlying conditions have been associated with a higher risk of embolism, the majority of embolic strokes occur in patients for whom no definite cause can be identified. Thus, it is imperative that markers of stroke risk be developed for this particular mechanism of cerebral infarction. In order to identify markers of embolic stroke risk, it is logical to focus on the hemostatic system, which regulates clot formation. Fibrinogen and von Willebrand factor (vWF) levels have been associated with a higher risk of ischemic stroke, and are elevated in highrisk cardiac conditions, such as atrial fibrillation. Recently, polymorphisms in the genes encoding vWF, fibrinogen, and factor XIII have been identified and linked to thrombotic events. These polymorphisms increase circulating levels of vWF and fibrinogen, respectively, and contribute to the formation of unstable thrombus due to ineffective fibrinogen to factor XIII crosslinking. In addition, a polymorphism of factor XHI has been identified, which increases its enzymatic activity and appears to result in the formation of unstable clot. The proposed project is a 5year, casecontrol study at a single academic medical center collecting genetic material and factor levels on consecutive cases of embolic stroke, nonembolic stroke, nonstroke controls. The Specific Aims of this project are to: 1) test the hypothesis that the allele frequencies for polymorphisms in the genes encoding vWF, fibrinogen, and factor XIII are higher in patients with embolic stroke than in nonembolic stroke subtypes or nonstroke controls, 2) test the hypothesis that the levels of vWF and fibrinogen will increase with age and that there will be an interaction between age and allele status affecting the vWF and fibrinogen levels, 3) establish the effects of conventional stroke risk factors on the expression of polymorphisms in the vWF, fibrinogen, and factor XIII genes, and 4) determine whether there is an association between allele status in the vWF, fibrinogen, and factor XIII polymorphisms and shortterm death or recurrent stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IDENTIFYING A GENE FOR CANINE CARDIOMYOPATHY Principal Investigator & Institution: Jakobs, Petra M.; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 10-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Atrial fibrillation (AF) causes significant morbidity, disability, and mortality related to heart disease and stroke in the human population. Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation and systolic contractile dysfunction and is an important cause of heart failure. In some canine breeds, DCM is a relatively common, lethal disease. A recent study of 500 Irish Wolfhounds (IW) found that 24% had DCM; 88% of these affected dogs also had AF. The DCM/AF phenotype appears to be inherited as an autosomal dominant trait. We have collected DNA and clinical data from a large family of IW in which AF and progressive DCM is segregating. Our hypothesis is that a mutation in a single gene causes DCM/AF in IW, and we propose to map this gene by linkage analysis and to use the tools of positional cloning and candidate gene analysis to identify the gene. One of the most common genetic causes of human DCM is mutation in the lamin A/C gene. The phenotype

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caused by lamin A/C mutations in such patients also includes conduction system disease and therefore resembles the DCM/AF phenotype in IW. In preliminary studies, we have excluded lamin A/C as the locus of the defect in IW. Hence our proposed work presents an ideal opportunity to identify a novel DCM/AF disease gene. If successful, this may lead to improved knowledge of the mechanisms of DCM and AF in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING ANTI-THROMBOTIC USE IN STROKE PREVENTION Principal Investigator & Institution: Beyth, Rebecca J.; Assistant Professor of Medicine; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by the applicant): Atrial fibrillation is a common disorder and an important risk factor for stroke. Evidence from controlled clinical trials shows that adjusted-dose warfarin decreases the risk of stroke by two-thirds. Clinical practice guidelines recommend that most atrial fibrillation patients receive life-long anticoagulation; only about one-third of atrial fibrillation patients receive it. This study is a randomized controlled trial of an intervention (the RBC) to increase the appropriate use of anti-thrombotic therapy (warfarin and aspirin) for stroke prevention in patients with chronic atrial fibrillation. The intervention is a tailored patient-specific risk-benefit consult (RBC) that incorporates the risks and benefits of anti-thrombotic therapy for stroke prevention using the American College of Chest Physicians guidelines and the Outpatient Bleeding Risk Index, a validated risk assessment for major bleeding. The intervention is aimed at primary care providers practicing in different clinical settings. Evidence-based specific recommendations about the use of anti-thrombotic therapy, as well as the quality of anti-thrombotic management will be formulated for each atrial fibrillation patient in the intervention physician's panel. The control and the intervention physicians will also receive performance feedback in the form of an Achievable Benchmark of Care (ABC) that informs them of the percentage of their patient panel with atrial fibrillation that is receiving anti-thrombotic therapy in relation to the other physicians (intervention or control) in their group. The primary outcome is the change, pre-to post-intervention, in the proportion of eligible patients with chronic atrial fibrillation who are prescribed anti-thrombotics. This will be measured by the proportion of the eligible patients in each physician's panel for whom anti-thrombotics are currently prescribed at baseline, 6-months, and 12-months. Secondary safety outcomes are the proportion of individuals in the physician's panel with stroke, the proportion of anticoagulated patients with major bleeds, and the proportion of total treatment time during which the International Normalized Ratio is below, above and within therapeutic range. This study will test a novel and generalizable approach to increasing the appropriate use of anti-thrombotic therapy in patients with atrial fibrillation in a community setting and the findings will provide valuable insight into stroke prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LINEAR LESION DEVICE Principal Investigator & Institution: Sherman, Jon; Vice-President; Enable Medical Corporation 6345 Centre Park Dr West Chester, Oh 45069 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2002 Summary: (provided by applicant): Atrial Fibrillation is an electrical malfunction of the upper pumping chambers of the heart causing major medical and lifestyle problems.

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The current treatments are pharmaceutical (side effects and minimal effectiveness), pacemakers (after destroying the electrical system of the heart, expensive and moderately effective), and electrically isolating areas of the heart using the MAZE procedure - surgically cutting the heart and sewing back together creating scar tissue to block malfunctioning electrical pathways. This MAZE procedure has proven to be nearly 100 percent effective, however it is long and extraordinarily difficult. Due to the promising concept, this approach is aggressively being investigated using ablation catheters and probes to create lesions. However, to isolate electrical pathways, a complete electrical block in the tissue must be made and these technologies are limited in their ability to create transmural lesions. With these technologies, charring and extensive atrial damage occur, which can increase risk of stroke. Our technology addresses these issues by incorporating RF Bipolar energy into a device that will quickly and safely create a transmural linear lesion, from endocardium to epicardium, in a single application while protecting the surrounding tissue. In Phase I we will fabricate a prototype and evaluate our lesions for transmurally and ability to electrically isolate tissue. PROPOSED COMMERCIAL APPLICATION: Our technclogy will overcome the limitations of the current methods of treating atrial fibrillation (AF) and can be used to treat AF during open-heart procedures and to reduce the occurrence of post-operative AF episodes. This market alone exceeds $1.2 BB/year. The devices that can be developed using this technology have a strong potential of being incorporated into minimally invasive procedures adding an additional $1.5 BB to the market potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MAGNETIC INTERVENTION

RESONANCE

GUIDED

ELECTROPHYSIOLOGY

Principal Investigator & Institution: Halperin, Henry R.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Ventricular tachyarrhythmias and atrial fibrillation are the most important arrhythmias affecting patients. They are the most frequently encountered tachycardias, account for the most morbidity and mortality, and despite much progress, remain therapeutic challenges. Invasive electrical studies of the heart (electrophysiologic studies) are often used in the diagnosis and therapy of arrhythmias, and may arrhythmias can be cured by selective destruction of critical electrical pathways with radiofrequency (RF) catheter ablation. A major limitation in studying arrhythmias in patients, however, is the lack of ability to accurately correlate anatomical and electrical information. Anatomy is derived from x-ray images, which are two-dimensional and have substantial anatomic ambiguity. Another major limitation is the lack of ability to visualize ablated areas of myocardium during catheter ablation procedures, making it difficult to confirm the presence of ablated lesions in the desired locations. We have developed ways of combining the anatomic information from magnetic resonance imaging (MRI), with electrophysiologic testing and catheter ablation. We hypothesize that magnetic resonance imaging, with transesophageal receivers, intracardiac receivers and MRI- compatible (non-magnetic) electrode catheters, can (1) provide accurate navigation of catheters without radiation, (2) provide the ability to visualize ablated lesions, and (3) aid in producing more accurate electrical maps. As a prototype for the development of new approaches to electrophysiologic testing and catheter ablation, this proposal addresses atrial fibrillation primarily. The imaging technologies developed in this project, should however, be broadly applicable to using MRI to guide interventional procedures in the heart in general, as well as in other organ systems. This project is an

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ongoing partnership between the Johns Hopkins University School of Medicine, the Johns Hopkins University Applied Physics Laboratory, Surgivision Inc., Robin Medical Inc., and Bard Electrophysiology, Inc., all of which have supplied resources to the project, and will continue to cost share. The School of Medicine is the lead institution and will be (1) developing specifications for advanced imaging and ablation catheter systems, (2) testing new technology as developed, and (3) performing interventional studies. The Applied Physics Laboratory is developing the technology for advanced intracardiac and transesophageal MRI receivers, and is developing software for 3dimensional reconstruction of MR imaging. Surgivision is developing clinical-grade versions of the MR receivers. Robin Medical is developing technologies for precisely localizing the tip of a catheter inside an MRI scanner. Bard Electrophysiology is supplying non-magnetic electrode catheters for use in the MRI scanner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM TACHYCARDIA

AND

BEHAVIOR

OF

SYMPTOMATIC

Principal Investigator & Institution: Pritchett, Edward L.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001 Summary: Investigators in the Divisions of Clinical Pharmacology and Cardiology at Duke University Medical Center have used the Rankin General Clinical Research Center to study patients with atrial fibrillation and other common disorders of the heart rhythm. Atrial fibrillation is the most common disorder of the heart rhythm requiring treatment with antiarrhythmic drugs, and it accounts for over one-third of all U.S. hospitalizations for arrhythmias. Patients with atrial fibrillation have their usually normal heart rhythm replaced by periods of rapid, irregular heart beating that may cause a sense of pounding in the chest, shortness of breath, chest pain, dizziness, or loss of consciousness. These periods may last for minutes or hours, or they may last indefinitely unless acute treatment is given by a physician. Studies conducted on the Rankin General Clinical Research Center have concentrated on elucidating the mechanism, clinical course, and optimal treatment of atrial fibrillation and related disorders of the heart rhythm. These studies have focused on measuring the frequency of spontaneous occurrence of atrial fibrillation and paroxysmal supraventricular tachycardia. Among 150 patients studied who had their antiarrhythmic drug therapy withdrawn, one-half had a spontaneous, symptomatic recurrence in about 3 weeks; in fact, about 1 in 5 had a symptomatic recurrence of their arrhythmia in less than 1 day. The average heart rate during recurrences was 132 beats/min for patients with atrial fibrillation and 198 beats/min for patients with paroxysmal supraventricular tachycardia. Among the patients with atrial fibrillation, about 1 in 9 had a second arrhythmia, atrial flutter, recorded along with fibrillation. The frequency of asymptomatic arrhythmias was approximately 12 times the rate of symptomatic arrhythmias. Curiously, quality of life was not affected by the frequency of arrhythmia occurrence. Similar methods were used to study patients with ventricular tachycardia who had an implanted cardioverter defibrillator (ICD). The frequency of ICD shocks in this population provided an estimate of the occurrence of ventricular tachycardia. About 1/3 of the patients had an episode of ventricular tachycardia within 1 month. Results of these studies are important for designing clinical trials of chronic antiarrhythmic drug therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Atrial Fibrillation

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Project Title: MECHANISMS OF LONG-TERM CARDIAC ION CHANNEL REGULATION Principal Investigator & Institution: Satin, Jonathan; Physiology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Heart failure (HF) and atrial fibrillation (AF) represent two of the most prevalent heart diseases in the U.S. In moderate to severe HF and in AF numerous phenotypic changes occur including a reduction of voltage-gated calcium channel current density. Changes in Ca channel expression may have farreaching effects on heart function due to their central role in excitation contraction coupling. Also, Ca channels have been implicated in excitation-transcription coupling. Thus alterations of Ca channel expression in the heart can also impact on disease progression. The principal voltage-gated Ca channel in the heart (CaV1.2) is extensively studied in the realm of its biophysical characteristics and second messenger modulation. However, very sparse information is available regarding longer term regulation of Ca channel expression. In this proposal we introduce a novel mechanistic hypothesis governing the functional expression of cardiac Ca channels in the sarcolemma of cardiac myocytes. In our preliminary data we show evidence for a ras-related monomeric Gprotein interaction with the CaV1.2 accessory subunit CaVb2. We propose to test the global hypothesis that G-protein interaction with CaVb subunits reduces Ca channel current density by competing for CaV1.2 binding. Moreover, our preliminary data shows strong evidence that this is a dynamic process that is modulated by chronic PKA activity. There are four specific aims that guide our experimental design: Aim 1 will characterize the time course and sub-cellular localization of nascent G-protein and CaVb complexes. Aim 2 will characterize the intracellular second messenger modulation of Gprotein-CaVb regulation of Ca channel current expression. Aim 3 will characterize the modulation of Ca channel current and G-protein modulation in native cells. Aim 4 will characterize the function of these G-proteins in heart function. These aims encompass approaches ranging from investigations of a purely molecular nature (protein-protein interactions), to in vitro model systems (heterologous expression of recombinant proteins), to native cell systems (primary isolates and cultures of heart cells), to the impact of a single class of G-proteins on tissue level heart function. This proposal may identify a novel class of therapeutic targets for alleviation of heart dysfunction in HF and AF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICRONUTRIENTS, STROKE AND COGNITION IN AGING Principal Investigator & Institution: Folstein, Marshal F.; Professor and Medical Director; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-DEC-2002 Summary: A major determinant of the quality of life for elderly individuals is the efficiency of their mental processes. Loss of neurocognitive functioning has been noted in elderly individuals; the severity of this loss ranges from simple memory deficits to profound dementia of the Alzheimer's variety. It is important to discover to what extent such functional decline is preventable and reversible. Specific to this project is the possibility that nutritional factors are important. Since estimates of the incidence of micronutrient deficiency in the elderly is quite large, intervention could significantly reduce the public health burden. The aim of this multidisciplinary study is to determine

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the prevalence of elevated homocysteine, brain disease, and cognitive decline in the homebound elderly. From 7500 homebound elderly, representative of all registered cases from a specified geographical area, a cohort of 1600 elders will be assessed. The assessment will include dietary history and serum nutrient levels, as well as comprehensive neuropsychological testing. Clinical examination and MRI scans will be performed on a subset of 400 subjects. Known risks for cognitive impairment such as diagnosed depression, anxiety, hypertension, diabetes, atrial fibrillation, medications, APOE, saturated fat intake, and mutations of MTHFR will be measured and included in analyses as covariates and effect modifiers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROSCOPIC ARRHYTHMIAS

DISCONTINUITIES

AS

A

BASIS

FOR

Principal Investigator & Institution: Spach, Madison S.; Professor; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-1993; Project End 30-NOV-2005 Summary: (the applicant's description verbatim): This is a competitive renewal application to the National Heart, Lung, and Blood Institute, where it has been administered in the past, for a continuing ROl grant on "Microscopic Discontinuities as a Basis for Arrhythinias." This renewal application is also designated in relation to Program Announcement 99-035 entitled "Impact of Aging on Atrial Fibrillation Development" because the proposed research is intended to link the initiation of atrial reentrant arrhythmias to changes in atrial microstructure that occur during aging in association with the escalating incidence of atrial fibrifiation. The research is focused on determining the mechanisms that lead to reentrant arrhythmias when changes in cardiac microstructure occur secondary to aging and disease. Implicit in this objective, the longterm goal is to understand the interrelationships between cell-to-cell current flow, ionic current flow through cell membranes, current flow in interstitial space, and propagation phenomena. The hypothesis of the project is that changes in cardiac microstructure due to aging and disease produce loading mechanisms that create conduction disturbances which induce and maintain reentrant arrhythmias. The specific aims are to: 1) determine how variations in the specific components of cardiac microstructure (e.g., distribution of gap junctions, cell morphology, variations of interstitial space) affect propagation at a cellular level; 2) develop a quantitative representation (model) of microscopic multidimensional propagation based on natural cell geometry, gap junction distribution, and interstitial space variations; and, 3) explore the sensitivity of conduction disturbances that occur with premature action potentials to variations in the different components of cardiac microstructure. Toward this end, we have established procedures to investigate these mechanisms by combining experimental measurements of intracellular, interstitial, and extracellular potentials with computer simulations that are based on multidimensional cellular models developed from documented microscopic substrates at different ages. Such computer models are essential since they provide a way to evaluate the role of the specific components of myocardial architecture at a microscopic level. Elucidation of the role of microscopic discontinuities has significant implications for new therapeutic approaches to arrhythmias associated with aging and structural heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODE SELECTION TRIAL IN SINUS NODE DYSFUNCTION (MOST) Principal Investigator & Institution: Lamas, Gervasio A.; Director of Cardiovascular Research And; Mount Sinai Medical Center (Miami Beach) 4300 Alton Rd Miami Beach, Fl 331402800 Timing: Fiscal Year 1999; Project Start 01-JUN-1995; Project End 31-MAY-2004 Summary: Approximately 130,000 pacemakers were implanted in the United States in 1993, at a cost of well over $1 billion. Pacemaker recipients may have single chamber ventricular or dual chamber pacemakers implanted. Dual chamber pacemakers are more expensive and less long-lived, but more physiologic, than single chamber pacemakers. The purpose of this 5 year mode Selection Trial (MOST) is to determine whether dual chamber rate modulated pacing (DDDR) in patients with sick sinus syndrome: improves event-free survival; leads to superior quality of life and functional status; is more costeffective than rate modulated single chamber (VVIR) pacing. The primary endpoint of MOST is a composite endpoint consisting of all cause mortality or stroke. The study is designed with a 90% power to detect a 25% difference between groups (p=0.05, 2 tailed). Secondary endpoints include health status and cost-effectiveness, total mortality, cardiovascular mortality, development of atrial fibrillation, development of pacemaker syndrome, and a combined clinical endpoint of non-fatal stroke, heart failure hospitalization, or death. Eligible, consenting patients with sick sinus syndrome will undergo DDDR pacemaker implantation and be randomly and noninvasively programmed to DDDR pacemaker implantation and be randomly and noninvasively programmed to DDDR or to VVIR. Enrollment will take place over 3 years, and followup will vary from 1.5 years to 4.5 years. Clinical and electrocardiographic data will be assessed by semi-annual visits, and quality of life will be assessed in a 1400 patient subset by yearly telephone interviews. Health care expenditures also will be assessed. Thus, this study will assess the patient benefits (clinical endpoints and health status), and societal benefits (cost effectiveness) of pacing mode selection in sinus node dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODIFICATION FIBRILLATION

OF

AV

NODE

FUNCTION

IN

ATRIAL

Principal Investigator & Institution: Mazgalev, Todor N.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 29-FEB-2004 Summary: Atrial fibrillation (AF), the most common sustained tachyarrhythmia, has fostered intense clinical and experimental interest. The significant discomfort, morbidity and mortality as well as the increasing prevalence among the aging population have generated an on-going multidisciplinary effort to understand the underlying pathophysiology. While atrial fibrillation is a multi-symptomatic decease, the high and irregular ventricular rate is one of the major undesirable consequences. It has a direct effect on the compromised mechanical performance. Since the AV node (AVN) is the only natural barrier for the bombarding atrial impulses, its function during AF can not be overestimated. Yet very little is known about the mechanisms underlying the AVN electrophysiology during AF. In the absence of safe and effective drug therapy, one of the most frequently used nonpharmacologic treatment strategies is radiofrequency ablation (RFA). This destruction necessitates permanent pacing with an undesirable alteration of the normal sequence of ventricular depolarization. We propose to use an

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integrated electrophysiologic-echocardiographic approach to explore a novel nondestructive strategy for ventricular rate control during AF. Our specific aims are: AIM number I. To investigate how functional or anatomic modification of the atrial inputs into the AVN affects ventricular rate during AF (in-vitro studies). AIM number 2. To investigate selective vagal stimulation of the AVN as a novel non-destructive mechanism for controlling ventricular rate during AF; also to determine how short and long term AF affects the electrical remodeling and vagal responsiveness of the AVN (invitro electrophysiologic and voltage-clamp studies). AIM number 3. To evaluate and compare the effects of localized AVN vagal stimulation versus AVN ablation on ventricular rate control and ventricular mechanical performance in spontaneous AF model in-vivo (electrophysiologic and echocardiographic studies). The long-term objectives are to provide the mechanistic basis for the development of new nondestructive clinical strategies for ventricular rate control during AF that are based on the normal AVN electrophysiology and provide better mechanical heart performance. This would benefit patients with pharmacologically resistant or surgically inappropriate treatment of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR FIBRILLATION

GENETIC

BASIS

FOR

FAMILIAL

ATRIAL

Principal Investigator & Institution: Brugada-Terradellas, Ramon; Assistant Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-JAN-2005 Summary: (the applicant's description verbatim): The overall objective is to identify the gene responsible for familial atrial fibrillation (Afib) located at 10q22, map novel chromosomal loci, and attempt to identify one of the novel genes. Afib, the most common sustained dysrhythm, affects over two million Americans and accounts for one third of all strokes over the age of 65 years. Therapy ineffective in preventing or eliminating Afib is directed at controlling the heart rate and preventing systemic emboli. Financial burden is estimated at $9 billion annually. A molecular basis for Afib has yet to be determined. Accordingly, we identified five families of 83 members, including 36 affected, with Atib segregating as a highly penetrant autosomal dominant trait and mapped the chromosomal locus to 10q22. We have collected data and DNA on 20 additional families, four of which are not linked to 10q22 indicating genetic heterogeneity, and have identified another 100 probands with familial atrial fibrillation but no data has been collected. Initial region of 11.3 cM contained several candidate genes which were sequenced in the family and no mutation was identified. Subsequently, 2 additional families with recombinants narrowed the region to a genetic distance of 0.6 cM and physical distance of 1.2 mb. A continuous contig of the region was assembled with a six-BAC tiling path. There are 38 ESTs present in the region and 2 of the ESTs tested so far show cardiac expression one of which appears to be a zinc finger transcription factor. Aim I is to amplify and sequence both genes represented by these 2 cardiac ESTs in 2 normal and 2 affected family members. If no mutation is found (Aim II), genes represented by the remaining 36 ESTs known to be present in the region will be analyzed and those expressed in the heart will be sequenced in family members for mutations (as in Aim 1). Subsequently, if no mutations are identified, we (Aim 3) will attempt to identify sequences that code for unknown genes by methods such as analyzing additional BAG sequences using computerized homology searches against DNA, protein and EST databases and also using gene prediction software. After identification, these novel genes will be characterized and sequenced as in Aims 1 and 2.

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Concurrently, additional pedigrees segregating familial atrial fibrillation (Afib) will be collected and the phenotypes of affected individuals carefully characterized by clinical and electrocardiographic analysis. DNA isolated from individuals will be analyzed for known DNA markers and subjected to genetic linkage analysis to determine if the disease in any of these families is linked to the 10q22 locus and if so, the responsible mutations will be identified. We will also map novel chromosomal loci responsible for Afib in those families not linked to 10q22. For the novel locus with the smallest critical region, we will initially pursue the responsible gene by sequencing candidate genes located in the region and subsequently, if necessary, will pursue positional cloning as in Aims 1-3 to identify the responsible gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR TARGETS IN ATRIAL FIBRILLATION Principal Investigator & Institution: Murray, Katherine T.; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Atrial fibrillation is the most common sustained cardiac arrhythmia and a major source of morbidity and mortality in the US. Available antiarrhythmic drugs are often ineffective and create serious proarrhythmia because channels in the ventricle are affected. In addition, electrical remodeling due to rapid stimulation in the atrium further perpetuates the arrhythmia, contributing to its refractory nature. The goal of this proposal is to identify novel targets for the treatment of atrial fibrillation by investigating the molecular basis of an atrial-specific ultra-rapid K+ current, IKur, and the early intracellular events that trigger the remodeling process. While the Kv1.5 gene product is an important component of IKur, our preliminary data indicate that this -subunit cannot fully recapitulate IKur, and we will test the hypothesis that co-assembly of additional channel subunits and/or signaling proteins occurs in vivo. The Kv1.5 complex will be isolated from human atrium and coassembled K+ channel lpha and/or etasubunits will be identified using antibody-based methods. Following heterologous expression of the proteins identified, electrophysiologic techniques will be used to confirm if the resultant K+ current phenotype is that of IKur. An analogous strategy will be used to determine the role of A-kinase anchoring proteins (AKAPs) in the Kv1.5 signaling complex. We will also test the hypothesis generated by our preliminary data that a Kv eta subunit can function as an AKAP. Finally, our initial results indicate that chronic rapid stimulation of atrial cells in culture leads to electrical remodeling, and this system will be used to test the hypothesis that the molecular events that trigger remodeling resemble those of cardiac hypertrophy, with activation of specific intracellular signaling cascades. The knowledge gained from these studies will improve our understanding of the molecular components of atrial electrophysiology, and should lead to the development of novel targets to treat atrial fibrillation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MRI COMPATIBLE ELECTRODE CATHETER SYSTEM Principal Investigator & Institution: Gelfand, Yakov; Lexmed Technologies, Inc. 7708 Crossland Rd Baltimore, Md 21208 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2004 Summary: (provided by applicant): Atrial fibrillation and ventricular tachyarrhythmias occurring in patients with structurally abnormal hearts are the most important arrhythmias in contemporary cardiology. They represent the most frequently

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encountered tachycardias, account for the most morbidity and mortality, and, despite much progress, and remain therapeutic challenges. Invasive studies of the electrical activity of the heart (electrophysiologic study) are often used in the diagnosis and therapy of arrhythmias, and many arrhythmias can be cured by selective destruction of critical electrical pathways with radiofrequency (RF) catheter ablation. Attempts at applying ablation to atrial fibrillation and ventricular tachycardia have been made. Success has been limited, however, by the long time duration of procedures, resulting from the difficulty of creating continuous linear lesions in a setting where areas of ablated myocardium cannot be directly visualized. Continuous linear lesions, without gaps, can block critical arrhythmogenic circuits and reduce the amount of electrically contiguous arrhythmogenic substrate, thereby eliminating arrhythmias. We hypothesize that magnetic resonance imaging (MRI), with MRI-compatible diagnostic and therapeutic systems; can allow electrophysiology studies and catheter ablation to be performed without x-ray radiation. We also hypothesize that this technology will provide the ability to visualize ablation lesions, which should greatly simplify production of continuous linear lesions, and should improve the effectiveness of ablation procedures in general. In addition to electrophysiology, these methods may be applicable to guiding other diagnostic and therapeutic techniques. In Phase I, we will complete a prototype steerable ablation catheter that will allow us to target any area of the endocardial surface of the heart. We will also develop integral filters for protecting the catheters from excessive heating during MR imaging. We will test the prototype catheters in animals to show that electrophysiology studies can be done under MR guidance alone, that lesions can be produced and imaged, that linear lesions can be produced, and that MRI has sufficient resolution to allow detection of significant gaps in the lesions. In Phase II, we will develop, test, and prepare for manufacturing and marketing, a clinical-grade version of the ablation system, and apply for FDA approval for testing the technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTERED STUDY OF STROKE GENETICS Principal Investigator & Institution: Meschia, James F.; Associate Professor; Mayo Clinic Jacksonville 4500 San Pablo Rd Jacksonville, Fl 32224 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 30-JUN-2005 Summary: Stroke is among the leading causes of death and disability in adults in the U.S. Over the past several decades, clinical studies have identified many environmental risk factors for stroke such as hypertension, diabetes mellitus and cigarette smoking. More recent evidence suggests that genetic components also contribute to the risk of stroke as well. Growth in the understanding of the human genome and advances in genetic epidemiology, make it possible to clarify the genetic contributions to complex diseases such as ischemic stroke. The overall long-term objective of this application is to search for regions of interest in the human genome that may harbor stroke susceptibility genes. The primary aim of the application is to collect DNA samples from 300 sibling pairs concordant for ischemic stroke and to perform a genome wide screen for genetic risk factors for ischemic stroke in these individuals. The screen will employ microsatellite markers spaced at a maximum of 20 centamorgan intervals. Secondary aims include: (1) identifying genetic regions of interest associated with ischemic stroke in adults below age 50 years and (2) identifying genetic regions of interest that are independent of stroke risk factors such as diabetes, hypertension, cigarette smoking, and atrial fibrillation. Probands will be screened for sibs concordant for stroke from patients with acute ischemic stroke who present to hospitals that are participating in the NIH-

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sponsored trial comparing carotid angioplasty/stenting to endarterectomy (CREST RO1-NS38384-01). A centralized stroke verification committee will assure and accuracy in stroke phenotyping. DNA banking will be done to permitted future collaborative efforts to study the genetic basis for stroke risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NATIONAL TRENDS IN OUTPATIENT QUALITY INDICATORS Principal Investigator & Institution: Stafford, Randall S.; Assistant Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: Despite the increasing attention on health care quality improvement in the U.S., the national quality of outpatient health care services has not been assessed. Particularly lacking are rigorous evaluations of trends in the quality of outpatient care for racial and ethnic minorities. This application will address this issue using data from the 1992-2001 National Ambulatory Medical Care Surveys (NAMCS) and National Hospital Ambulatory Medical Care Surveys (NHAMCS). Its aims are to: 1) construct a set of outpatient quality indicators, 2) assess quality of care at the national level using the selected indicators, 3) evaluate time trends in these indicators, and 4) determine patient, physician and organizational predictors of quality of care, with a particular focus on racial/ethnic minorities. A set of 27 proposed quality indicators will provide a quantitative assessment of quality and will cover: 1) recommended medications (e.g., warfarin in atrial fibrillation), 2) antibiotic use (e.g., antibiotics in viral respiratory infections), 3) physician counseling/disease management (e.g., dietary counseling in diabetes), 4) diagnostic testing (e.g., screening urinalysis tests), and 5) medication errors (e.g., risky drug-drug interactions). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW DRUGS FOR TREATMENT OF ATRIAL FIBRILLATION Principal Investigator & Institution: Lacerda, Antonio E.; Chantest, Inc. 14656 Neo Pky Cleveland, Oh 44128 Timing: Fiscal Year 2001; Project Start 07-AUG-2001; Project End 30-APR-2002 Summary: Atrial fibrillation (AF) is the commonest cardiac arrhythmia and in its chronic form affects more than two million patients in the USA. AF is associated with cardiac and non-cardiac diseases. About 10% of cases have no obvious cause (lone AF). Stroke is the commonest complication with a 25% greater risk than control in older age groups. Drugs that block sodium, potassium and calcium channels provide the customary treatment. All of these drugs may have toxic side effects because their ion cannel targets are present in ventricle where block may produce lethal arrhythmias. Our long-term objective is to develop a satisfactory drug for AF. As a first step we have identified a novel target that is limited to human atrium and should therefore be free from the risk of ventricular arrhythmias. The specific aim of this proposal is to discover novel, selective drugs acting on this atrial-delimited target for the treatment of AF. The novel target will be expressed in cell lines for use in high throughput functional screens of small compounds derived from directed and diversity libraries. Confirmed leads will be fully characterized and two to five preclinical drug candidates should be available within two years. PROPOSED COMMERCIAL APPLICATIONS: Atrial fibrillation is a very common disease for which there is no satisfactory treatment. A drug that has high efficacy with little toxicity would have great therapeutic and commercial value. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NONINVASIVE ASSESSMENT OF ATRIAL FIBRILLATION Principal Investigator & Institution: Kynor, David B.; Creare, Inc. Box 71, Etna Rd Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-MAR-2003 Summary: Atrial arrhythmias are extremely common and are often associated with significant morbidity and mortality. The ability to develop and prescribe new treatments for atrial arrhythmias depends on the availability of better diagnostic tools that are simple, inexpensive, and effective enough to support their use for screening large numbers of patients. During Phase I, we developed signal processing algorithms that permit noninvasive assessment of patients suffering from atrial fibrillation. T algorithms were tested on patient data and found to assist clinicians in predicting patient response to cardioversion in an attempt to terminate the arrhythmia and restore sinus rhythm. During Phase II, we will investigate alternate algorithms for identification and classification of atrial arrhythmias. Our goal is development of a tool that will allow the clinician to rapidly identify specific arrhythmias and measure the progress of individual patients through different courses of therapy. PROPOSED COMMERCIAL APPLICATION: The technology developed under this program could be used in diagnostic devices like electrocardiogram monitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OPTICAL COHERENCE TOMOGRAPHY FOR PULMONARY CIRCULATION Principal Investigator & Institution: Brezinski, Mark E.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-MAR-2006 Summary: (provided by applicant): This program is a continuation of NIH R29 HL.55686, extending optical coherence tomography (OCT) imaging to the evaluation of pulmonary arterial and venous circulation. OCT is a recently developed method of high resolution imaging which was developed for the evaluation of unstable plaque through this program. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than sound. It's resolution, between 4 and 20 um, is up to 25 X higher than anything available in clinical medicine. Among the observations under NIH R29 HL1155686, OCT demonstrated a feasibility for the identification of vulnerable plaque, superior resolution to high frequency ultrasound (IVUS), and in vivo imaging in a rabbit model. In addition, a catheter based delivery system and high speed data acquisition system were developed. The technology is now being commercialized for in vivo human imaging. In this proposal, we will be extending OCT imaging to the pulmonary vasculature. In particular, in addition to +/-aracterizing normal pulmonary vasculature, a focus will be placed on the evaluation of pulmonary hypertension and the guidance of pulmonary vein ablation for atrial fibrillation. Pulmonary hypertension, an increase in pulmonary blood pressure, is a leading cause of mortality worldwide. Current methods of assessing the pulmonary vasculature are inadequate or dangerous. A method of high resolution assessment of the vasculature could be a powerful tool in the management of this disorder. Atrial fibrillation is a common disorder associated with a high incidence of stroke. It has recently been demonstrated that a significant portion of atrial fibrillation can be cured by ablation of foci in the pulmonary veins. However, this procedure is associated with a high incidence of pulmonary vein stenosis. A technology capable of controlling the degree of ablation could substantially improve the outcome of this procedure. The hypothesis of this proposal is that OCT demonstrates

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a feasibility for high resolution assessment of pulmonary vasculature, both for diagnosis and guiding interventions. The hypothesis will be tested through the following specific aims: Aim 1. Development of an OCT Imaging Catheter, Aim 2. Assessing the Pulmonary Veins Ablation in an Animal Model, Aim 3. Vascular Assessments In Vitro, Aim 4. OCT Elastography and Aim 5. OCT Imaging will be performed in an Animal Model of PTN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FIBRILLATION

OPTIMAL

ANTITHROMBOTIC

THERAPY

IN

ATRIAL

Principal Investigator & Institution: Gage, Brian F.; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: Although clinical trials demonstrated that antithrombotic therapy can reduce the risk of stroke in carefully selected patients with atrial fibrillation (AF), many patients were excluded from these trials because of their advanced age, comorbid conditions, or both. Exclusion of the very elderly has led to uncertainty about the effectiveness and safety of stroke prophylaxis for patients older than 75 years. To address the shortcoming of available data, we will compare outcomes in a cohort of 3600 Medicare beneficiaries with AF who were prescribed warfarin, aspirin, or neither upon hospital discharge. In collaboration with 5 Peer Review Organizations (PROs) we will use Medicare Part A claims data to determine how prescribing antithrombotic therapy affects the rates of death, stroke, and hemorrhage. The broad, long-term objective of the proposed study is to decrease the mortality and improve the quality of life of patients who have AF. In pursuit of this dual objective, the study has 3 specific aims: (l) to determine the effectiveness of prescribing antithrombotic therapy in very elderly patients with AF; (2) to determine the safety of prescribing antithrombotic therapy in very elderly patients with AF; and (3) to conduct a formal cost-benefit analysis of prescribing antithrombotic therapy in very elderly patients with AF. To assess effectiveness, we will determine how antithrombotic therapy affects the rate of death or nonfatal stroke. To assess safety, we will determine how antithrombotic therapy affects the rate of major hemorrhage. To perform the cost-benefit analysis we will use the observed rates of death, stroke, and hemorrhage in a decision model to estimate the effect of antithrombotic therapy on quality- adjusted survival and costs. Results from our pilot study, in combination with other literature, demonstrate that the proposed project has potential to save lives, prevent strokes, and reduce health care expenditure. In our pilot study we found that the absolute reduction in death and nonfatal stroke attributable to antithrombotic therapy may be greatest in patients older than 75. If the proposed project confirms the results of the pilot study, it will clarify the risks and benefits of prescribing antithrombotic therapy to the very elderly and elucidate the optimal stroke prophylaxis for this growing population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND ATRIAL FIBRILLATION Principal Investigator & Institution: Van Wagoner, David R.; Director, Basic Cardiac Electrophysiolog; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 10-JUN-2001; Project End 30-APR-2005 Summary: More than two million Americans suffer from various forms of atrial fibrillation (AF). AF is a major cause of stroke and an independent risk factor for

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mortality. Following initiation, AF tends to self-perpetuate, due in part to electrophysiological remodeling of the atria. The high rate activity of the fibrillating atria has multiple electrophysiological, metabolic, and hemodynamic consequences. AF increases atrial oxygen consumption 2-3 fold, and increases the availability of reactive oxygen species (oxidative stress). In post-cardiac surgery patients the increase in oxidative stress is striking, and one-third of these patients develop postoperative AF. The goal of this application is to determine the relationship between oxidative stress and the electrophysiological remodeling that occurs during AF. Oxidative stress modulates the activity of several ion channels (Ca, K, and ryanodine receptor) important for normal atrial function. In preliminary studies, we have demonstrated that rapid pacing of canine atria results in increased oxidative injury, and that treating patients with vitamin C (an antioxidant) can decrease the incidence of post-operative AF. Thus, we propose that increased oxidative stress is a key link between the major risk factors for the development of AF, and that the electrophysiological remodeling accompanying the onset of atrial fibrillation is the result of oxidative stress. To test our hypothesis, parallel studies will be performed in patients and in a rapidly paced canine model of AF. The aims of this study are: 1) to determine the impact of oxidative stress on action potentials, Ca, K currents, and shortening in isolated atrial myocytes; 2) to assess the oxidative injury in atrial tissue using biochemical and immunohistochemical techniques, and to correlate this with in vivo electrophysiological properties; 3) to correlate plasma levels of oxidative stress markers and anti-oxidant capacity with electrophysiological changes in vivo; 4) to prospectively evaluate antioxidant therapies, with respect to their capacity to decrease levels of markers of oxidative stress and attenuate the electrophysiological remodeling that occurs in fibrillating canine atria; and finally, to directly evaluate the impact of vitamin C on the incidence of post-operative AF in patients. Successful therapies should prevent oxidative Injury, blunting the reduction in atrial effective refractory period that accompanies the onset of AF, minimizing its perpetuation, and facilitating Its termination. We anticipate that these early interventions will prove to be the most effective approach to the long term treatment and prevention of AF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PH III: AZIMILIDE CONTROLLED TRIAL Principal Investigator & Institution: Bahnson, Tristram D.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001 Summary: Purpose: The purpose of this study is to assess the safety of long-term use of azimilide in patients with atrial fibrillation/flutter and/or paroxysmal sypraventricular tachycardia. Atrial fibrillation is the most common cause of clinically significant sustained tachycardia and occurs in up to 12% of individuals over age 75. Incidence increases with each decade of life. Furthermore, atrial fibrillation is responsible for up to 1/3 of thromboembolic strokes. Anticoagulation, pharmacologic control of the ventricular response, and antiarrhythmic pharmacotherapy have been the main stays of treatment for atrial fibrillation. However, the selection of available antiarrhythmic drugs, and their efficacy, are limited. Specifically, of available antiarrhythmic agents, only sotalol and amiodarone are considered safe in patients with underlying heart disease. Atrial fibrillation is most often associated with valvular, ischemic, or hypertrophic heart disease, limiting the use of available type I antiarrhythmic agents. Further, the class III agents sotalol and amiodarone are potent negative chronotropic agents which limits their usefulness in patients with atrial fibrillation in association with sinus node disease (brady-tachy syndrome), also a frequent clinical occurence.

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Accordingly, there is an important need for the development of new antiarrhythmic drugs with the following characteristics: 1) safety in patients with structural heart disease. 2) absence of significant negative chronotropic effects. One such drug is Azimilide, a class III antiarrhythmic agent with very weak bradycardic effects at test dosing levels, and which appears to be safe when used in individuals with structural heart disease. Methods: This is a multi-center double-blind, placebo-controlled, parallel design clinical trial studying a daily oral dose of 125 mg of azimilide dihydrochloride. Results: Results of the double blind trial of azimilide has been reported in preliminary form (n=89) with demonstration of a significant decreases in mean time to AF recurrence in azimilide treated patients (130 days; 100mg/d and 125mg/d) comparted with control (17 days, p (log rank) of 0.002). Significance: The significance of this clinical research program is to test the safety and efficacy of this promising new antiarrhythmic drug in the treatment of atrial fibrillation. Atrial fibrillation is the most common cause of clinically significant sustained tachycardia and occurs in up to 12% of individuals over age 75. Incidence increases with each decade of life. Furthermore, atrial fibrillation is responsible for up to 1/3 of thromboembolic strokes. Future Plans: Phase III trials of Azimilide are ongoing, and it is anticipated that currently enrolled patients will be followed prospectively for a total of 24 months. After completion of the phase III trials of Azimilide for treatment of atrial fibrillation, further studies of the safety and efficacy of this new antiarrhythmic agent to control paroxysmal atrial fibrillation in specific clinical circumstances are envisioned. These studies will be conducted under separate protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOGENOMICS OF ARRHYTHMIA THERAPY Principal Investigator & Institution: Roden, Dan M.; Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-JUL-2005 Summary: Sudden death due to ventricular fibrillation kills 250,000-500,000 Americans each year and up to 5,000.000 American have a history of atrial fibrillation, which is associated with stroke, heart failure, and increase mortality. There is substantial interindividual variability in response ti ion channel blocker, B-blocker, and warfarin, drugs widely used in the therapy of arrhythmias; some patients display beneficial effects, while others exhibit lack of efficacy or even life- threatening adverse effects. The hypothesis to be tested here is that allelic variants in candidate genes- implicated by an emerging understanding of molecular physiology and pharmacology-contribute to such variable drug responses. Work in our laboratories and elsewhere has identified allelic variants, and their functional consequences, in candidate genes, including drug metabolizing enzymes, ion channel proteins, and components of intracellular signaling systems. We have 4 Specific Aims: (1) to expand polymorphism discovery, focusing on new candidate genes; to determine frequencies of common polymorphisms in defined ethnic groups; and to ealuate variant protein function in vito; (2) to assess the role of allelic variants in modulating atrial and ventricular fibrillation and their response to drugs; (3) to determine the value of pre-prescription genotyping for QT prolonging antiarrhythmics and for warfarin; and (4) to use acute challenge with ibutilide and atenolol in sib-pairs to identify familial component(s) in drug responses (QT and heart rate change), and to determine the role of candidate and gene-gene interactions in modulating those responses. The studies will be supported by expertise in clinical pharmacology, clinical and basic electrophysiology, genetic epidemiology, bioinformatics, and polymorphism discovery and allele typing. This research will

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rigorously test the concept that advances in genetic science and molecular pharmacology can be combined to improve drug therapy. The outcomes will be not only improved drug therapy of arrhythmias, but also further development of appropriate methods to exploit genomic science to enhance drug therapy in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSIOLOGIC BENEFITS OF BIVENTRICULAR PACING IN CHF Principal Investigator & Institution: Hamdan, Mohamed H.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-AUG-2003 Summary: (The applicant's description verbatim): Acute biventricular (BV) pacing has been shown to result in hemodynamic improvement in patients with left ventricular dysfunction. Based on these studies, the effect of long term BV pacing on exercise tolerance and quality of life are being assessed in large prospective trials. What remains unknown are the effects of BV pacing on sympathetic activity, a known predictor of cardiac mortality, and on the incidence of ventricular arrhythmias. We hypothesize that in patients with LV dysfunction 1) BV pacing decreases sympathetic activity compared to intrinsic conduction in the presence of intraventricular conduction delay 2) BV and LV pacing improves hemodynamics and decreases sympathetic activity compared to right ventricular pacing 3) BV pacing decreases the inducibility of ventricular arrhythmias and 4) that this latter effect is due to preexcitation and prolongation of the coupling interval in the "slow" zone of the tachycardia circuit. To test these hypotheses, consecutive patients referred to the arrhythmia section at the Dallas VAMC with LV dysfunction and an indication for electrophysiologic evaluation will be enrolled in the study. During phase 1 and 2, arterial pressure, central venous pressure and muscle sympathetic nerve activity using microneurography will be recorded during sinus rhythm, atrial pacing (in patients with a QRS greater than 150msw) and atrialventricular pacing (RV, LV or BV). Pacing will be performed at a rate 10 beats faster than sinus rhythm. During phase 3 and 4, we will assess the effect of BV pacing on the inducibility of ventricular arrhythmias and the associated electrophysiologic changes. The outcome of this study will have a great impact on our management of patients with congestive heart failure. A reduction in sympathetic activity, demonstrated first with acute BV pacing and later with long term pacing, may have a beneficial effect on mortality. Similarly, a reduction in inducibility of ventricular arrhythmias, if present with long term pacing, may have an impact on the survival and on our management of patients with implantable defibrillators and frequent shocks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POST CORONARY BYPASS ATRIAL ARRHYTHMIC PREDICTION RULE Principal Investigator & Institution: Passman, Rod S.; Medicine; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The proposed study seeks to develop and validate a clinical prediction rule for post-coronary artery bypass grafting (CABG) atrial fibrillation and atrial flutter (AF). These arrhythmias occur in 20-40% of the 500,000 patients undergoing CABG, and increase the morbidity, cost, and length of stay associated with the procedure. Though several studies have suggested that prophylactic therapy with beta-adrenergic blockers decreases the risk of post-CABG AF, this efficacy

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Atrial Fibrillation

has not been universally appreciated. As a result, several new prophylactic therapies have been introduced, though some with significant toxicities associated with them. It is therefore imperative to identify a priori those individuals most at risk of developing post-CABG AF, as well as those unlikely to develop this endpoint. In this manner, those individuals most at risk of developing post-CABG AF may be targeted for prophylactic therapy, while those in a low risk category may be spared the exposure to a potentially deleterious therapy from which they are less likely to derive benefit. Additionally, the identification of a high-risk subgroup would allow for the execution of smaller randomized controlled trials, and may provide insight into the etiology of post-CABG AF. The study is a retrospective cohort study designed to identify pre-, intra-, and postoperative variables which may be associated with post-CABG AF. From these results, a clinical prediction rule will be formulated. Validation of the prediction rule will then take place in a prospective cohort study using a different group of patients from which the rule was derived. This will allow for the assessment of both validity and generalizability. The candidate has committed himself to a career as an independent investigator, with an interest in the application of rigorous epidemiologic techniques to questions of importance in cardiac electrophysiology, his area of clinical expertise. This project will be an integral part of the candidate?s career development plan and his maturation as an epidemiologist, cardiac electrophysiologist, and clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRIMARY AND SECONDARY PREVENTION OF CHD AND STROKE Principal Investigator & Institution: Ornstein, Steven M.; Family Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: The principal aim of the application is to study the impact of a quality improvement model using academic detailing and electronic medical records (EMR) on adherence with clinical practice guidelines for prevention of cardiovascular disease and stroke in primary care settings. The long-term objective of the research is to validate a method implementing evidence- based medicine in primary care, using an approach combining information tools and behavioral change theory. Investigators from the Medical University of South Carolina's Center for Health Care Research (CHCR) will conduct the study in 22 affiliated Practice Partner Research Network (pPRNet) sites across the United States. Project investigators have developed and refined the model to be tested in this application in previous research. The model is termed "Quality Improvement through Electronic Medical Records (QIT-EMR)." The primary prevention guidelines studied will be screening for hypertension and hypertension control, screening for hyperlipidemia, and hormone replacement therapy for postmenopausal females. The secondary prevention guidelines will be cholesterol lowering for patients with coronary heart disease (CHD) and diabetes mellitus (DM), beta-blockers for patients with a history of myocardial infarction, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients with heart failure, oral anticoagulant therapy for patients with atrial fibrillation, and glycemic and blood pressure control in patients with DM. The study will be a three-year randomized controlled clinical trial. It will test the hypothesis that practices that receive the QITEMR model interventions will have greater improvement in the proportion of patients who receive the primary and secondary preventive interventions and achieve target outcomes than do comparison practices. Data for the study will be obtained from the existing EMR at each study practice. Control group practices will receive information about the clinical practice guidelines, and quarterly reports detailing their adherence

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with them. Intervention group practices will receive identical information and participate in four practice site visits by study investigators, three investigator meetings, and ongoing communication to implement the QIT-EMR model. A formative evaluation of the interventions will be conducted. At the conclusion of the trial, the impact and cost of the intervention will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEIN KINASE A MODULATION OF KV1.5 Principal Investigator & Institution: Williams, Christine M.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: In humans, IKUR - is an atrial-specific, ultra-rapid, delayed rectifier K+ current that is increased by (beta-adrenergic stimulation. Although the cloned K+ channel, Kv1.5 is the principal molecular correlate of IKUR, our preliminary data suggest that co-assembly of other factors or proteins is required to recapitulate the native current and its modulation by protein kinase A (PKA). We will test the hypothesis that Kv1.5 is part of a multi-protein complex that includes an A Kinase Anchoring Protein (AKAP) that targets PKA to the channel. Using electrophysiologic techniques, the role of AKAP co-expression with Kvl.5 to enable the PKA response will be examined. In addition, I will test the hypothesis that an auxiliary K+ channel beta subunit can function as an AKAP. Finally, I will investigate what molecules coassemble with Kv1.5 in human atria. Given the atrial specificity of this K+ current in humans, novel strategies to treat atrial-based arrhythmias such as atrial fibrillation may result. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF STRETCH IN FOCAL ATRIAL FIBRILATION Principal Investigator & Institution: Arora, Rishi; Medicine; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The candidate wishes to pursue an academic and research career in cardiac electrophysiology, with a primary focus on the pathophysiology of atrial arrhythmias in animal models. He has dedicated one of the last two years of his fellowship (in clinical cardiac electrophysiology) to the animal lab, and has already done considerable work in understanding the electrophysiology of the pulmonary veins and their role in the genesis of atrial fibrillation (AF). A better understanding of the underlying mechanisms of AF is crucial to the development of effective preventive and therapeutic strategies for this arrhythmia. Recent observations suggest that in a large number of patients, AF may be originating from focal "triggers" in the pulmonary veins. The electrophysiologic properties of these focal sources are poorly defined, however. With the aid of high-resolution optical mapping, the candidate has recently described heterogeneous conduction and repolarization within the pulmonary veins, and has demonstrated micro re-entry in this region. This project aims to further characterize the electrophysiologic properties of canine pulmonary veins, in response to acute or chronic atrial stretch. It is expected that this mentored award will allow the candidate to develop the analytical as well as the technical and methodological skills he requires to develop into an independent physician-scientist. The candidate's mentors have a long track record of pathbreaking investigation in basic and clinical arrhythmia research; in addition, the animal research facilities at the Krannert Institute are amongst

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the finest in the world. Specific Aim 1 will attempt to study the effects of acute balloon stretch/dilatation on the electrophysiology of normal, canine pulmonary veins. Both high-density endocardial catheter mapping (in the intact dog) and high-resolution optical mapping (in a Langendorff preparation) will be utilized to study the pulmonary veins. In Specific Aim 2, we will examine electrophysiologic characteristics of the pulmonary vein in the setting of chronic atrial dilatation. A canine model of chronic mitral regurgitation will be used for this purpose. Optical mapping will be performed in a Landendorff preparation to determine the electrophysiology in the intact vein. Histologic and gap junction studies will be also performed as part of this aim. In addition, we will study the electrophysiology of isolated pulmonary vein cardiomyocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLOW RELEASE PROPAFENONE SYMPTOMATIC RECURRENCE OF A

IN

PREVENTION

OF

Principal Investigator & Institution: Biblo, Lee; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001 Summary: The purpose of this study is to test the effectiveness of propaferone slow release (Rythmol-SR) in preventing symptomatic atrial fibrillation. This research project will also gather information relating to the side effects experienced with Rythmol-SR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOFTWARE PROMOTES NCEP/AHA PROVIDER GUIDELINE ADHERENCE Principal Investigator & Institution: Baruch, Lawrence; Coecare.Com, Llc 185 Bridge Plaza N, Ste 306 Fort Lee, Nj 07024 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Cardiovascular disease continues to be the leading cause of mortality and morbidity in the United States To assist health care practitioners in their integration of new information into clinical practice, professional organizations such as the National Cholesterol Education Program Expert Treatment Panel (ATP Ill), American Heart Association (AHA), American College of Cardiology (ACC), and Expert Treatment Panel (ATP III), Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), develop guidelines to promote evidence-based standards of care in the management of cardiovascular disease. Despite the comprehensive nature and widespread dissemination of these guidelines, target parameters are not being achieved, and patients are not managed optimally. These diseases include achievement of lipid and blood pressure goals, usage of antiplatelet or anticoagulant therapy in patients with coronary artery disease and atrial fibrillation, usage of 13-blockers in patients post myocardial infarction, and the usage of t3-blockers and converting enzyme inhibitors in patients with systolic left ventricular dysfunction. The failure of implementation of optimal evidenced based guideline care has been attributed to a number of reasons including lack of knowledge of the guidelines and the failure of the guidelines to instruct the health care provider on strategies to implement the guidelines in individual patients. To facilitate the incorporation of these treatment guidelines in everyday medical practice, the Cardiac Goal Program software has been developed to prompt entry of data essential to the management of cardiovascular disease, based on Class I or Grade A recommendations

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using established guidelines, into standardized, computerized forms with a reminder system. The aims of the proposal are the incorporation of NCEP cholesterol treatment algorithms into the existing Cardiovascular Goal Program, employ usability methodologies, including in-depth interviews and focus groups with physicians, nurses, and physicians assistants, and refine the existing software based on the feedback from the practitioner's and retest the feasibility. If this automated clinical information and decision support system is successful and widely implemented, the best outcomes from care for chronic cardiovascular disease may be achieved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPATIO-TEMPORAL PERIODICITY IN ATRIAL FIBRILLATION Principal Investigator & Institution: Jalife, Jose; Professor of Pharmacology; Pharmacology; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 20-JUN-2003 Summary: This is an application to produce a quantitative analysis of the dynamics and mechanisms of acute sustained atrial fibrillation (AF) in Langendorff-perfused sheep hearts. A major goal is to determine the role played by discrete atrial structures in the dynamics of wave propagation and mechanisms of AF. The general hypothesis is that the intricate 3D musculature of the atria plays a major role in the maintenance of AF. Specifically, it is proposed that acute AF induced by burst pacing depends on 1) uninterrupted periodic reentrant activity within discrete areas of the atria, with the shortest reentrant circuits acting a dominant frequency source that drives the atria and maintains sustained AF activity; and, 2) the high frequency of wave fronts emanating from the source areas interact with anatomical and/or functional obstacles, which produces fragmentation of the wave front and wavelet formation. Preliminary experimental results using Fast Fourier Transforms (FFTs) show that the dominant frequency peak of overall atrial electrical events correlates with local areas of periodic activity (i.e., uninterrupted patterns of reentry within the left atrium). Preliminary results also show that areas with aperiodic activity (multiple variable wavefronts) have relatively low local AF activation frequencies versus the periodic areas that have higher local activation frequencies, and these areas are separated by gross anatomical structures between the two atria, such as the atrial septum and Bachmann's bundle. There are three specific aims. 1) To combine epicardial optical mapping with frequency analysis and statistical techniques to identify discrete areas of spatiotemporal periodicity, which are identified as areas that have similar recurrent AF activation intervals with similar activation sequences. Once these areas have been identified, their contribution to the frequency content of the global atrial electrogram will be determined. 2) To use the optical mapping system and electrical signals recorded with 16 electrodes as a combined approach for spectral analysis of the electrical activity of a large number of atrial areas during AF. The optical signals, along with the bipolar electrical recordings at multiple sites, will be used as a systematic approach to localize the sources that produce the dominant frequencies in the FFTs. 3) To provide a quantitative understanding of the mechanisms of wavelet formation and of the complex patterns of activation spread that characterize AF. Mechanisms will be defined in the context of nonlinear dynamics by using the concepts of the general theory of wave propagation in excitable media, and newly developed analytical tools will be used to account for the fragmentation of wave fronts by phase singularity points that produce wavelets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STROKE PREVALENCE & RISK W/ HYPERTENSION, DIABETES, TIA & CARDIOVASCULAR FACTORS Principal Investigator & Institution: Wiebers, David O.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SUBCUTANEOUS RHUIL4 IN PATIENTS WITH RA Principal Investigator & Institution: St Clair, Eugene W.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001 Summary: Purpose: The purpose of the present study is to determine the safety and tolerability and potential clinical efficacy of subcutaneous doses of recombinant human IL-4 (rHuIL-4) in patients with rheumatoid arthritis (RA). RA is a chronic inflammatory disease of unknown etiology. It is characterized by synovial inflammation with frequent progression to articular cartilage and bone destruction. The synovial inflammatory response in RA consists predominately of T lymphocytes, mostly T helper cells (Th), with fewer numbers of macrophages and B lymphocytes. The Th cells can be divided into two overlapping subpopulations with important functional significance, Th1 and Th2 cells. Th1 cells secrete IL-2 and interferon- and regulate cell-mediated responses. Th2 cells secrete IL-4, IL-5, and IL-10, and mediate humoral responses. Most Th cells in the rheumatoid joint belong to the Th1 subpopulation. The synovial tissue in RA exhibits other features typical of a cell-mediated response, including hypervascularity, upregulation of cell adhesion molecules, and overexpression of pro-inflammatory cytokines such as IL-1 and tumor necrosis factor (TNF)-. IL-4, a cytokine produced by Th2 cells and macrophages, has primarily immunosuppressive and anti-inflammatory properties. The inhibitory effects of IL-4 have been observed in animal models of arthritis where it can ameliorate joint inflammation. Methods: The study is a multicenter, double-blind, placebo-controlled, escalating dose (0.5, 1.0, and 2.0 5g/kg) clinical trial with a dosing period of 6 weeks. The main outcomes for the study are the frequency and severity of adverse effects and the American College of Rheumatology Core Disease Measures. Results: The study has been completed. A total of four patients were enrolled at this site. The study population was predominantly female (3/1) and Caucasian. The study drug was well tolerated and did not cause any serious adverse event reactions. One patient, a Caucasian male, was seen during the reporting period. There were two serious adverse events that occurred during the course of the study. One patient with a past history of supraventricular tachycardia, hypertension, and hypothyroidism (managed with Levothyroxin) was admitted to the hospital for atrial fibrillation. Because of the cardiotoxicity profile of IL-4 in preclinical trials, the investigator considers the atrial fibrillation to be possibly related to the study drug. The second serious adverse event concerned a patient who was admitted for hip replacement surgery. This patient had long- standing disease and a past history of multiple joint replacements. IL-4 treatment did not improve disease measures. Significance: RA is widely believed to be a Th1-mediated disease, although the data to support this hypothesis is circumstantial. For example, Th1 cells are associated with cellular immune responses, which seems to fit with the characteristics of rheumatoid joint inflammation, and T cell clones isolated from synovial tissue of RA patients most often secrete Th1 cytokines. Additional insights into whether RA is a Th-driven

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41

response in RA may be obtained by examining the treatment and biological effects of cytokines that downregulate Th1 responses. Future plans: Since, interleukin-4 did not yield the expected effect in RA patients, there are no plans for future studies at this time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURGICAL TREATMENT OF CARDIAC ARRHYTHMIAS Principal Investigator & Institution: Damiano, Ralph J.; Professor; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 08-AUG-1983; Project End 31-JUL-2007 Summary: Atrial fibrillation (AF) is the most common arrhythmia in the world, and a significant source of morbidity and mortality. Unfortunately, antiarrhythmic drugs have had limited efficacy and numerous side effects. Transvenous ablation techniques require prolonged, often multiple, procedures and have had high complication rates and questionable long-term efficacy. Over the last two decades, our laboratory has developed two successful surgical approaches for the treatment of AF. The Maze and Radial procedures have the best-documented long-term results in the treatment of atrial fibrillation, with over 90% of patients remaining arrhythmia-free at 10 years. Despite their proven efficacy, few surgeons around the world actually perform these procedures, both because of their invasiveness and complexity. Moreover, these operations are far from perfect, and still result in significant morbidity in terms of postoperative atrial arrhythmias, conduction disturbances, and atrial dysfunction. Our goal in this competing renewal is to develop a less invasive procedure with more widespread applicability by moving from an anatomically based operation that was designed to eliminate all possible mechanisms of AF to a mapping-directed procedure that addresses the specific focal mechanisms responsible for AF in each particular patient. To accomplish this goal and to evaluate the physiologic consequences of our interventions, the following specific aims are proposed: 1) Develop a real-time algorithm using intraoperative epicardial mapping to identify focal sources and substrates for AF to allow for mapping-directed therapy. 2) Develop less-invasive surgical procedures for the treatment of AF based on real time mapping data and the assessment of the physiological consequences and mechanistic insight from the operations. 3) Develop techniques to evaluate atrial function non-invasively to allow for the precise assessment of the hemodynamic consequences of surgery for AF. 4) Determine the causes of postoperative arrhythmias associated with surgical procedures to ablate AF, and modify these procedures to minimize their occurrence. If we can achieve these aims, the thousands of chronic AF patients yearly who undergo valvular and coronary surgery will have their arrhythmia cured in the operating room at the time of surgery, and our surgical treatment will become a viable option to a lifetime of anti-arrhythmic drug therapy and anticoagulation for millions of patients with lone AF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: SURGICAL TREATMENT OF CARDIAC ARRHYTHMIAS Principal Investigator & Institution: Boineau, John P.; Medical Science Service; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 08-AUG-1983; Project End 31-JUL-2003 Summary: This renewal application requests five years' support for work now in continuous progress for over 15 years at Washington University. Dr. John Boineau, the new PI, has replaced Dr. James Cox, the former P1, who transferred to Georgetown University Hospital. Dr. Cox remains as a special consultant. The broad aims continue to

42

Atrial Fibrillation

be the direct or surgical ablation of cardiac arrhythmias. The emphasis of the current renewal is focused upon the development of a new procedure, the radial incisions approach (RIA), to eradicate atrial fibrillation (AF) and restore atrial transport function and is directed primarily toward patients undergoing surgery for valvular or ischemic heart disease. Conventional valve or CABG surgery does not eliminate and may not prevent AF in these patients. The availability of an effective means of eradicating this arrhythmia in these patients at the time of surgery would permit control of rate and rhythm, limit embolic stroke, and improve cardiac performance, outcome, and the quality of life. Whereas the Maze and RIA assume randomly distributed and changing reentry which are eliminated without prior activation mapping, new data indicate that some forms of AF result from (spatially) stable reentry which can be identified by new mapping methods and focally ablated. Thus, a second project is directed toward map guided, focal cryoablation of AF. This could be performed off bypass as a more limited and rapid alternative to the more extensive and (bypass) time consuming RIA procedure. A third project is targeted at prevention and correction of postoperative atrial flutter (AFL) after the Fontan operation in congenital heart patients or after lung transplant surgery. Studies will be performed in both realistic animal models with atrial enlargement and patients with AF and AFL and will center about the use of new automated, 3-D mapping techniques and rapid numerical analysis of potentials recorded simultaneously from to 512 electrodes during the arrhythmias. Preliminary observations indicate that the proposed studies are feasible, will provide new information regarding the different mechanisms of AF and AFL that are related to atrial enlargement and/or atrial surgery, and this data will be used to develop the new surgical ablation techniques to control or prevent these arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED PHOSPHOLAMBAN

ABLATION

AND

ALTERATION

OF

MOUSE

Principal Investigator & Institution: Kranias, Evangelia G.; Professor; Pharmacology & Cell Biophysics; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-JUL-1981; Project End 31-MAY-2004 Summary: Evidence from in vitro and in vivo studies indicates that phospholamban is an important regulatory phosphoprotein in the mammalian heart. Dephosphorylated phospholamban is an inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase and phosphorylation of phospholamban relieves in inhibitory effects. Phospholamban is phosphorylated at distinct amino acids by three different protein kinases, namely serine 10 by protein kinase C, serine 16 by cAMP-dependent protein kinase, and threonine 17 by Ca2+-calmodulin-dependent protein kinase. Phospholamban has also been shown to be phosphorylated in vivo by both cAMP-dependent and Ca2+- calmodulin-dependent protein kinases during isoproterenol stimulation of intact hearts. Phosphorylation of phospholamban and the accompanied increases in the Ca2+-uptake rates by the SR have been postulated to the responsible for the increases in the rate of myocardial relaxation during beta-adrenergic stimulation of the heart. However, the exact role of phospholamban in the regulation of contractility and whether phosphorylation of this protein alone is directly responsible for and sufficient to cause the alterations in myocardial relaxation observed during beta-adrenergic stimulation is not presently known. Thus, our goal is to design animal models, which will elucidate the role of phospholamban in the regulation of SR function, myocardial contractility and the responses of the heart to beta-agonists. Specifically, we propose to target the phospholamban gene locus in murine embryonic stem cells. The targeting will be

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43

directed towards ablation of the protein or introduction of site specific mutations in the coding region. Unlike other transgenic systems, the chromosomal context will be maintained and other systems will be used to generate mice, which will be analyzed at the molecular genetic, biochemical and physiological levels. Ablation of phospholamban will allow definition of the basic function of this protein in the contractile performance of control hearts, their responses to beta-agonists and the role of phospholamban in heart disease, where evidence indicates that its mRNA expression levels are significantly reduced. Generation of phospholamban mutants will provide information on structure/function relationships in phospholamban in the intact animal. This genetic approach carried out via gene targeting technology will provide fundamental information on the basic function of phospholamban and the physiologic and pathophysiologic significance of alterations in its content or its primary structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THORACIC VEINS AND SUSTAINED ATRIAL FIBRILLATION Principal Investigator & Institution: Chen, Peng-Shen; Director, Pacemaker and Icd Clinic; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The broad and long-term objective of this research project is to test the hypothesis that repetitive rapid activities (RRAs) within the thoracic veins underlie the mechanisms of sustained atrial fibrillation (AF). Recent studies show that paroxysmal AF episodes are often initiated and maintained by RRAs from the thoracic veins, including pulmonary veins, the vein of Marshall, and the superior vena cava. Sustained AF includes both persistent AF and permanent AF. While RRAs in the thoracic veins underlie the mechanisms of paroxysmal AF, the relation between RRAs and the mechanisms of sustained AF is less clear. The purpose of the present grant proposal is to perform studies in humans and in a canine model to test the Thoracic Vein Hypothesis of sustained AF. Specific Aims: (1) We will perform intraoperative mapping studies and radiofrequency (RF) ablation studies in human patients with sustained AF to demonstrate the presence of RRAs in human thoracic veins, and to compare the activation rate within the thoracic veins and those in the LA and RA. (2) Effects of sympathetic stimulation, beta blockade and antiarrhythmic drugs on a canine model of sustained AF induced by rapid pacing of the thoracic veins. We will perform chronic rapid pacing of the extrapericardial portion of a canine thoracic vein to induce sustained AF. High density computerized mapping will be used to determine whether or not there are RRAs from all thoracic veins. We will then determine if the RRAs can be suppressed or enhanced by pharmacological or electrophysiological intervention. (3) Thoracic veins in dogs can fibrillate without being connected to the atria. Using RF ablation technique, one of the thoracic veins will be electrically isolated at its junction from the remainder of the atria. Chronic rapid pacing will be performed from that vein to determine if sustained RRAs can be induced within the vein without being electrically connected to the atria. (4) Termination of sustained AF by thoracic vein isolation. We will induce AF by chronic rapid pacing in a thoracic vein. During second surgery, we will perform epicardial RF catheter ablation to electrically isolate all thoracic veins from the atria. (5) Immunocytochemical studies of the thoracic veins. We will use immunocytochemical staining techniques to determine if there are pacemaking cells in the thoracic veins, and whether or not the location of the pacemaking cells correlate with the sites of RRAs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THYROID ACTION IN THE HEART Principal Investigator & Institution: Dillmann, Wolfgang H.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 01-MAY-1979; Project End 31-AUG-2007 Summary: (provided by applicant): Thyroid hormone (T3) markedly influences the contractile and electrophysiological function of the heart. Recent results from T3 receptor (TR) knockout (KO) mice indicate that TR alpha KO mice have decreased contractile function and heart rate but TR beta KO mice have normal cardiac function. TR alpha 1 is the predominant TR isoform (TRI) in the heart and the TR alpha KO cardiac phenotype could therefore result from quantitative and overlapping or unique qualitative TR alpha 1 effects. In Aim I we will explore the quantitative and/or qualitative nature of the TR isoform effects on the heart in rescue type of experiments using viral vectors, crosses of TRI KO mice with TRI transgenic mice and TR alpha and TR beta gene promoter knock in mice expressing tagged TR alpha 1 or TR beta 1 in cardiac myocytes. Contractile function and gene expression profiles using conventional mRNA quantitation and DNA microarrays will be determined. In addition we will use TR alpha exon 3 LoxP floxed mice, which allow for myocyte specific inducible deletion of TR alpha, to determine developmental influences and effects of other organs on cardiac function. We recently generated these mice. In Aim II we will determine in wild type mice with pressure overload induced heart failure (HF) exhibiting decreased TR and T3 levels if the diminished contractile phenotype can be rescued using viral vector or transgenic animal based TR alpha 1 or TR beta 1 substitution in combination with TR ligands. With adequate rescue by TR beta 1 novel T3 analogues, with preferred TR beta 1 binding like GC1, can be used which have markedly diminished effects on heart rate compare to T3, potentially allowing for contractile rescue without unwanted electrophysiological effects. These studies will provide new insights into a specific type of non-thyroidal illness syndrome resulting from HF which presents a very significant medical problem. In Aim III the basis for T3 mediated increased in heart rate will be explored by identifying T3 responsive pacemaker ion channels in the sinus node. In addition the mechanisms underlying hyperthyroidism induced atrial fibrillation will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TOWARDS FIBRILLATION

A

NON-INVASIVE

THERAPY

FOR

ATRIAL

Principal Investigator & Institution: Scherlag, Benjamin J.; Medicine; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Atrial fibrillation (AF) has been called the arrhythmia of the 21st century since it is the most common arrhythmia whose prevalence increases as the population ages. Recent clinical studies have suggested that trains of rapid electrical discharges from the pulmonary veins induce paroxysmal (P) or episodic AF. The mechanism by which this focal activity leads to PAF is unknown. Therefore, our initial studies have concentrated on this mechanism providing for a 4 step strategy towards developing a non-invasive therapy for PAF 1) Demonstration that local autonomic nerve stimulation at the base of the pulmonary veins can cause the conversion of rapid focal firing from the pulmonary veins into PAF. 2) Demonstration that low level electrical stimuli applied to the vagosympathetic trunks can condition the cardiac ganglia so that stimuli applied to the latter will manifest a significant alteration

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in the threshold for induction of PAF. 3) Utilize time varying electromagnetic fields (EMFs) applied to the cervical vagosympathetic trunks in order to significantly alter the AF threshold. 4) Since magnetic components of EMFs penetrate soft tissues and bone unattenuated, our final approach will employ a large 18" Helmholtz coil by which the EMF will be applied across the chest to induce low-level electrical stimulation of intrinsic cardiac nerves. Again, the objective is to demonstrate electrical conditioning of the local cardiac autonomic nerves in order to alter baseline conditions for AF induction. In this developmental phase, all of these studies will be acutely performed in Napentobarbital anesthetized dogs. Our long-term objectives relate to the extension of the previously described strategies to animal models of chronic or sustained AF which if applied to the clinical arena would profoundly alter the treatment of these arrhythmias in man. This new therapeutic approach could be utilized as a non-invasive application or incorporated into an implantable device for treatment of patients with PAF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSCRIPTIONAL REMODELING IN CARDIAC ARRHYTHMIAS Principal Investigator & Institution: George, Alfred L.; Director, Division of Genetic Medicine a; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Electrical remodeling describes the electrophysiological changes occurring in chronic cardiac diseases associated with an increased susceptibility to arrhythmias. Changes reflecting remodeling in readily measured electrophysiologic characteristics (action potential duration, individual ionic currents) have been observed in large animal models with arrhythmias closely resembling those in humans. In the dog model of chronic complete AV block (CAVB), biventricular hypertrophy occurs along with substantial increases in action potential duration that render the animals prone to developing Torsades de Pointes during exposure to QT-prolonging antiarrhythmic agents. Similarly in chronic atrial fibrillation (both human and various pacing-induced animal models), atrial electrical remodeling produces a cellular substrate that perpetuates the arrhythmia (?atrial fibrillation begets atrial fibrillation?). Evidence points to long term changes in gene expression as an important element in the genesis of these arrhythmia prone states. However, our knowledge of the identity and temporal sequence of changes in gene expression underlying these two conditions is rudimentary. In this Project, we will use microarray technology to survey global patterns of transcriptional remodeling in dog hearts that occur following chronic AV block and with pacing-induced atrial fibrillation. This work requires that we develop a gene array from a panel of canine expressed sequence tags that we have started to collect. Development of a canine microarray will enable us to examine changes in gene expression in hypertrophied ventricular myocardium of CAVB dogs and assess differences between subgroups of animals that exhibit susceptibility or resistance to drug-induced Torsade de Pointes. We will also be able to characterize the transcriptional remodeling in atrial myocardium associated with induction of atrial fibrillation in dogs subjected to rapid atrial pacing. Robust statistical analyses of microarray data will be used to direct appropriate validation experiments using separate methods. These studies will provide new insights into the pathogenesis of arrhythmia susceptibility and contribute to identifying potential new targets for therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Atrial Fibrillation

•

Project Title: TRENDS IN AND OUTCOMES OF MEDICATION USE IN OLDER ADULTS Principal Investigator & Institution: Psaty, Bruce M.; Professor, Medicine and Epidemiology; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 30-JUN-2005 Summary: This proposal, the 2nd revision of a competing continuation last reviewed in March 2000, is an ancillary study to the Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary disease and stroke in 5888 older adults. This revision addresses questions such confounding and interpretation raised by the Study Section. In CHS, medical conditions are well characterized, and participants are followed closely for events. CHS clinic visits, where medication data had been collected, ended in 1999, and the NHLBI plans to provide full support only for events follow-up for an additional 5 years. This project provides support to 4 Field Centers to continue to collect medication data by telephone interview and to CHS scientists to continue analyses of these data. In a pilot study of 74 subjects, agreement between in-clinic and telephoneinterview medication inventories was excellent. The purpose is to assess use of cardiovascular medications and their associations with outcomes among older adults. To date, the project is associated with 26 publications and 7 presentations. The aims, which focus on the use of cardiovascular medications and their association with events, are consistent with PA99-097 entitled, "Diversity in Medication Use and Outcomes in Aging Populations." One innovative feature of this study is the age of the cohort. At baseline in 1989-90, the mean age of the CHS cohort was 72.8 years, and as of Oct 1999, the mean age of the survivors was 81.2 years: 2290 (55.9 percent) of the 4095 surviving CHS participants are 80 years of age or older. Over the last several decades, the results of randomized clinical trials and meta-analyses have helped to define optimal care for patients with cardiovascular disease or with risk factors for cardiovascular disease. Guidelines have been formulated for the care of patients with coronary disease or with risk factors such as elevated levels of cholesterol or blood pressure. But information about the implementation of guidelines or the effect of clinical trials on practice patterns is often lacking for older adults; and we also lack information about the efficacy and safety of most medications for older adults, especially the oldest old, who are the fastest growing segment of the US population. The aim of this project is to describe the use of various cardiovascular medications and their association with outcomes among older adults. The project has good to excellent power for a number of hypotheses, including: the use of ACE inhibitors and beta- blockers in subjects with heart failure or coronary disease and their association with total mortality; the use of warfarin in patients with atrial fibrillation and their association with stroke or death; the use of blood pressure and lipid lowering medications and their association with cardiovascular events and cognitive function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ULTRASONIC EPICARDIAL ABLATION FOR TREATING ATRIAL FIB. Principal Investigator & Institution: Bernardi, Richard B.; President; Spectrasonics Imaging 489 Devon Park Dr Strafford, Pa 19087 Timing: Fiscal Year 2003; Project Start 08-APR-2003; Project End 30-NOV-2003 Summary: (provided by applicant): Spectrasonics Imaging, in collaboration with Riverside Research Institute (RRI) and Columbia Presbyterian Hospital proposes a Phase I effort to design, acquire and evaluate a linear array high intensity focused

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ultrasound (HIFU) transducer for the application of epicardial ablation for treating atrial fibrillation (AF). The transducer is to have both HIFU and pulse echo imaging capability - the latter for monitoring tissue change during the ablation and thereby controlling the process. HIFU has advantages over other ablation energy sources (e.g. RF) because the energy can be focused to produce homogeneous transmural lesions. The long term objective is to develop a system that will safely and effectively ablate the left atrium in a pattern that will block conduction from aberrant foci causing AF. The initial patient population will be AF patients undergoing cardiac surgery such as coronary artery bypass grafts (CABG) and mitral valve replacement (MVR). Eventually it may be possible to conduct the procedure thoroscopically and treat a much wider AF population. The Phase 1 program will involve determining frequency, size, focal and intensity requirements, devising a practical transducer design, and then modeling the design to verify beam shape and the resulting tissue temperature and damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VERY FIBRILLATION

LOW

ENERGY

CARDIOVERSION

FOR

ATRIAL

Principal Investigator & Institution: Wolf, Patrick D.; Biochemical Engineering; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: Internal atrial defibrillation is a successful therapy for the treatment of atrial fibrillation(AF). Current internal atrial defibrillators(IAD) use conventional defibrillation technology to deliver high energy shocks with a high likelihood of success. The applied shock strength of 3-10 Joules is above a patient's pain threshold and this limits the broad application of IAD therapy. A technology is proposed that utilizes multiple very low energy (less than.5J) shocks(VLES) with a low probability of first shock success but a high cumulative probability of conversion. A telemetry system will be implanted in an ovine model of AF. The combined animal model and telemetry system will be used as a test bed for VLES atrial cardioversion. The telemetry unit transmits 4 electrograms a distance of 10 meters and delivers continuous and programmed pacing by remote control. This system will be enhanced by adding pressure monitoring and VLES circuitry. It will be used 1) to characterize electrical remodeling and to track changes in infra-atrial pressure induced by the rapid pacing protocol and 2) to measure the energy that corresponds to a 5 percent level of success, and 3) to test three strategies for increasing the VLES probability of success. The three strategies are: 1) pre-VLES overdrive pacing 2) pre-VLES non-linear dynamics based pacing, and 3) use of class III antiarrhythmic drugs with VLES. Epicardial mapping will be used to identify the mechanism of VLES defibrillation and to characterize the effects of the 3 enhancement strategies. The work proposed in this grant will advance the science of remote testing in unanesthetized animals, will characterize the development of electrical modeling and myocardial pathology produced by rapid pacing in sheep, and will test a total of four strategies for very low energy atrial defibrillation. These advances will increase our understanding of the progression of AF and allow a successful therapy for this debilitating disease to be more broadly applied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRTUAL ELECTRICAL-ANATOMICAL IMAGING OF THE HEART Principal Investigator & Institution: Khoury, Dirar Shafiq.; Assistant Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030

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Atrial Fibrillation

Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2005 Summary: (Provided by Applicant): Atrial fibrillation (AF) is the most common heart rhythm disorder: it affects more than two million Americans, is responsible for one-third of all strokes over the age of 65 years, and annually costs 9 billion dollars to manage. Furthermore, about 300,000 Americans die of sudden cardiac death annually, primarily due to ventricular rhythm disorders (ventricular tachycardia (VT and fibrillation) which result in intractable, extremely rapid heartbeats. Unfortunately, current pharmacological therapy for managing these disorders is often ineffective, thereby shifting emphasis to nonpharmacological therapy (e.g. ablation and pacing). Catheter ablation has been successful in managing many atrial and a few ventricular rhythm disorders. However, due to limitations in present mapping techniques, brief, chaotic, or complex rhythms such as AF and VT cannot be mapped adequately, resulting in their unsuccessful elimination. Advancing the management of abnormal heartbeats is contingent on developing mapping techniques that identify their mechanisms, localize their sites of origin, and elucidate effects of therapy. Our objective is to develop a catheter-based, cardiac electrophysiological imaging technique that simultaneously maps multiple endocardial electrograms on a beat-by-beat basis and combines three-dimensional activation-recovery sequences with endocardial anatomy. The hypothesis is that virtual electrical-anatomical imaging of the heart based on (1) cavitary electrograms that are measured with a noncontact, multielectorde probe and (2) three-dimensional endocardial anatomy that is determined with integrated, intracardiac echocardiography (ICE), provides an effective and efficient means to diagnose abnormal heartbeats and deliver therapy. Therefore, we will: (1) build a noncontact, electrical-anatomical imaging catheter-system that carries both a multielectrode catheter-probe for acquiring cavitary electrograms from multiple directions, and a central ICE catheter for acquiring endocardial anatomical images; (2) advance novel mathematical methods to compute endocardial electrograms and reconstruct three-dimensional activation-recovery sequences based on noncontact cavitary probe electrograms and geometry determined by ICE; and, (3) prove the utility of virtual electrical-anatomical imaging in the canine beating heart by characterizing models of AF, myocardial infarction, and VT and identifying their components, and by quantifying ablation lesions as assessed by both electrical and echocardiographic criteria. The proposed catheter can be introduced into the blood-filled cavity without surgery and provides three-dimensional electricalanatomical images on a beat-by-beat basis. With this approach, one can pinpoint the site of origin and type of abnormal heartbeats and advance their therapy. In line with a Bioengineering Research Grant, the research develops a system the outcome of which is to improve the benefit-risk and benefit-cost relationships of patient care and advance heart rhythm-related research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VOLTAGE DEPENDENT K+ CHANNELS IN HEAT--KV15 ALPHA SUBUNI Principal Investigator & Institution: Hill, Joseph A.; Associate Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: The broad, long-term objectives of this proposal are to determine the specific function and macromolecular structure of Kv1.5 (a voltage-dependent K+ channel alpha subunit possibly involved in repolarization of the cardiac action potential). This work is based on the hypothesis that the Kv1.5 alpha subunit is a component of a K+ channel involved in phase repolarization of the cardiac action potential (and hence functions as a

Studies

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receptor of anti-arrhythmic drugs with Class III action). This work is a first step in the long process of dissecting the proteins that mediate repolarizing outward current in the heart. The Specific Aims are 1) compare the electrophysiological characteristics of delayed-rectifier K+ currents in wild-type cardiac myocytes with those from mutant animals lacking a functional Kv1.5 gene, 2) compare ambulatory electrocardiograms in mice from three genetic backgrounds (wild-type, Kv1.5-null, heterozygotic) at baseline and after exposure to drugs that modulate myocyte repolarization, and 3) determine whether the absence of Kv1.5 in vivo modulates protein and transcript levels of other alpha and/or beta subunits. Increasingly, disorders of repolarization are causally implicated in many malignant cardiac arrhythmias. These arrhythmias underlie sudden cardiac death which is a major killer of Americans today causing an estimated 400,000 deaths per year. Increasingly, we treat atrial fibrillation the commonest arrhythmia, afflicting 1 percent of persons older than 60 years old-with repolarization-active antiarrhythmic agents. The structural basis of repolarizing current in heart is presently poorly characterized. However, the ion channels that mediate repolarizing K+ current serve as receptors for anti-arrhythmic drugs with Class III activity, one of our major weapons against these devastating arrhythmias. The research design centers on comparing physiologic parameters and biochemical features of wild-type mice with mice deficient in Kv1.5. The methods to be used are biochemical and immunological (Western blots, immunoprecipitation) and electrophysiological (patch clamping, ambulatory electrocardiography). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “atrial fibrillation” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for atrial fibrillation in the PubMed Central database: •

A Novel Approach to the Prevention of Thromboembolism in Atrial Fibrillation. by Ganjoo AK.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101167

•

Ablation of atrial fibrillation: a procedure come of age? by Wharton JM.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59627

•

Anticoagulation therapy for patients with atrial fibrillation. by Hart RG.; 2000 Oct 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80541

3 Adapted 4

from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Atrial Fibrillation

•

Anticoagulation therapy for patients with atrial fibrillation. by Connolly SJ.; 2000 Nov 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80300

•

ASA or low-molecular-weight heparin in the initial management of acute ischemic stroke complicating atrial fibrillation? by Farquhar D.; 2001 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80756

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Atrial fibrillation associated with sumatriptan. by Morgan DR, Trimble M, McVeigh GE.; 2000 Jul 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27444

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Atrial fibrillation in a primary care practice: prevalence and management. by Ceresne L, Upshur RE.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116583

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Atrial fibrillation in chronic dialysis patients in the United states: risk factors for hospitalization and mortality. by Abbott KC, Trespalacios FC, Taylor AJ, Agodoa LY.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149358

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Atrial Fibrillation: The Most Common Arrhythmia. by Wyndham CR.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101077

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Determination of the Target Ventricular Rate in Patients with Atrial Fibrillation by Evaluation of Ventriculoarterial Coupling. by Nobuoka S, Hatano S, Nagashima J, Yoshida A, Adachi H, Imai Y, Shibamoto M, Ikeda K, Miyake F.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116734

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Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. by Devereaux PJ, Anderson DR, Gardner MJ, Putnam W, Flowerdew GJ, Brownell BF, Nagpal S, Cox JL.; 2001 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59994

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Identification of patients with atrial fibrillation in general practice: a study of screening methods. by Sudlow M, Rodgers H, Kenny RA, Thomson R.; 1998 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28628

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Implementing evidence based medicine in general practice: audit and qualitative study of antithrombotic treatment for atrial fibrillation. by Howitt A, Armstrong D.; 1999 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27873

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Lone atrial fibrillation in vigorously exercising middle aged men: case-control study. by Karjalainen J, Kujala UM, Kaprio J, Sarna S, Viitasalo M.; 1998 Jun 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28577

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Long-term management of atrial fibrillation: Rhythm or rate control? by Kovacs KA.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149258

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New insights into the mechanisms and management of atrial fibrillation. by Khairy P, Nattel S.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134179

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Physicians' perceptions of the benefits and risks of warfarin for patients with nonvalvular atrial fibrillation. by Bungard TJ, Ghali WA, McAlister FA, Buchan AM, Cave AJ, Hamilton PG, Mitchell LB, Shuaib A, Teo KK, Tsuyuki RT.; 2001 Aug 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81330

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Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. by Hellemons BS, Langenberg M, Lodder J, Vermeer F, Schouten HJ, Lemmens T, van Ree JW, Knottnerus JA.; 1999 Oct 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28250

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Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness. by Kalra L, Yu G, Perez I, Lakhani A, Donaldson N.; 2000 May 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27364

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Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269]. by Mant JW, Richards SH, Hobbs FD, Fitzmaurice D, Lip GY, Murray E, Banting M, Fletcher K, Rahman J, Allan T, Raftery J, Bryan S.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201020

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Rhythm versus rate control for atrial fibrillation management: what recent randomized clinical trials allow us to affirm. by Nattel S.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149253

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Risk of mortality in a cohort of patients newly diagnosed with chronic atrial fibrillation. by Ruigomez A, Johansson S, Wallander MA, Garcia Rodriguez LA.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99044

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Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation. by Taylor FC, Cohen H, Ebrahim S.; 2001 Feb 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26572

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The impact of patients' preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis. by Protheroe J, Fahey T, Montgomery AA, Peters TJ.; 2000 May 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27382

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with atrial fibrillation, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “atrial fibrillation” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for atrial fibrillation (hyperlinks lead to article summaries): •

A 60-year-old woman with atrial fibrillation. Author(s): Singer DE. Source: Jama : the Journal of the American Medical Association. 2003 October 22; 290(16): 2182-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570954&dopt=Abstract

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A case series of sotalol-induced torsade de pointes in patients with atrial fibrillation-a tale with a twist. Author(s): Tan HH, Hsu LF, Kam RM, Chua T, Teo WS. Source: Ann Acad Med Singapore. 2003 May; 32(3): 403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854385&dopt=Abstract

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A fatal complication due to radiofrequency ablation for atrial fibrillation: atrioesophageal fistula. Author(s): Sonmez B, Demirsoy E, Yagan N, Unal M, Arbatli H, Sener D, Baran T, Ilkova F. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 281-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842562&dopt=Abstract

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A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT). Author(s): Carlson MD, Ip J, Messenger J, Beau S, Kalbfleisch S, Gervais P, Cameron DA, Duran A, Val-Mejias J, Mackall J, Gold M; Atrial Dynamic Overdrive Pacing Trial (ADOPT) Investigators. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 627-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932592&dopt=Abstract

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A randomized clinical trial of the efficacy of radiofrequency catheter ablation and amiodarone in the treatment of symptomatic atrial fibrillation. Author(s): Krittayaphong R, Raungrattanaamporn O, Bhuripanyo K, Sriratanasathavorn C, Pooranawattanakul S, Punlee K, Kangkagate C. Source: J Med Assoc Thai. 2003 May; 86 Suppl 1: S8-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866763&dopt=Abstract

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A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. Author(s): Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D'Agostino RB, Larson MG, Kannel WB, Benjamin EJ. Source: Jama : the Journal of the American Medical Association. 2003 August 27; 290(8): 1049-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941677&dopt=Abstract

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Ablate and pace revisited: long term survival and predictors of permanent atrial fibrillation. Author(s): Queiroga A, Marshall HJ, Clune M, Gammage MD. Source: Heart (British Cardiac Society). 2003 September; 89(9): 1035-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923021&dopt=Abstract

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Ablation of atrial fibrillation: awaiting the new paradigm. Author(s): Ellenbogen KA, Wood MA. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 198-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875750&dopt=Abstract

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Amiodarone for conversion of atrial fibrillation. Author(s): Botelho RJ. Source: Anesthesiology. 2003 September; 99(3): 756; Author Reply 757. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960566&dopt=Abstract

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Amiodarone reduces the incidence of atrial fibrillation after coronary artery bypass grafting. Author(s): Yagdi T, Nalbantgil S, Ayik F, Apaydin A, Islamoglu F, Posacioglu H, Calkavur T, Atay Y, Buket S. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1420-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830063&dopt=Abstract

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Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians' fears often unfounded. Author(s): Man-Son-Hing M, Laupacis A. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1580-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860581&dopt=Abstract

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Atrial fibrillation after adult lung transplantation. Author(s): Kogan A, Ilgaev N, Sahar G, Kramer M, Saute M, Aravot D, Berman M, Vidne BA. Source: Transplantation Proceedings. 2003 March; 35(2): 679. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644093&dopt=Abstract

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Atrial fibrillation after conventional and off-pump coronary artery bypass grafting: two opposite trends in timing of atrial fibrillation occurrence? Author(s): Siebert J, Lewicki L, Mlodnicki M, Rogowski J, Lango R, Anisimowicz L, Narkiewicz M. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 March; 9(3): Cr137-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640343&dopt=Abstract

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Atrial fibrillation and stroke prevention. Author(s): Hart RG. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1015-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968083&dopt=Abstract

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Atrial fibrillation as a risk factor for stroke recurrence. Author(s): Penado S, Cano M, Acha O, Hernandez JL, Riancho JA. Source: The American Journal of Medicine. 2003 February 15; 114(3): 206-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637135&dopt=Abstract

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Atrial fibrillation: classification, pathophysiology, mechanisms and drug treatment. Author(s): Markides V, Schilling RJ. Source: Heart (British Cardiac Society). 2003 August; 89(8): 939-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860883&dopt=Abstract

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Atrial fibrillation: current surgical options and their assessment. Author(s): Gillinov AM, Blackstone EH, McCarthy PM. Source: The Annals of Thoracic Surgery. 2002 December; 74(6): 2210-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643434&dopt=Abstract

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Atrial fibrillation--more evidence that it's here to stay. Author(s): McAnulty JH. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849667&dopt=Abstract

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Atricure bipolar radiofrequency clamp for intraoperative ablation of atrial fibrillation. Author(s): Gillinov AM, McCarthy PM. Source: The Annals of Thoracic Surgery. 2002 December; 74(6): 2165-8; Discussion 2168. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643412&dopt=Abstract

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Autonomic modulation preceding the onset of atrial fibrillation. Author(s): Maisel WH. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522494&dopt=Abstract

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Balancing risk in atrial fibrillation. Author(s): Ali SN, Hardman SM. Source: The Practitioner. 2001 May; 245(1622): 357. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11373966&dopt=Abstract

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Balancing the risks of stroke and upper gastrointestinal tract bleeding in older patients with atrial fibrillation. Author(s): Man-Son-Hing M, Laupacis A. Source: Archives of Internal Medicine. 2002 March 11; 162(5): 541-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871922&dopt=Abstract

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Baseline characteristics of patients with atrial fibrillation: the AFFIRM Study. Author(s): AFFIRM Investigators. Atrial Fibrillation Follow-up Investigation of Rhythm Management. Source: American Heart Journal. 2002 June; 143(6): 991-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075254&dopt=Abstract

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Basic mechanisms of atrial fibrillation. Author(s): Van Wagoner DR. Source: Cleve Clin J Med. 2003 July; 70 Suppl 3: S2-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882402&dopt=Abstract

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Beating-heart surgical treatment of atrial fibrillation with microwave ablation. Author(s): Maessen JG, Nijs JF, Smeets JL, Vainer J, Mochtar B. Source: The Annals of Thoracic Surgery. 2002 October; 74(4): S1307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400806&dopt=Abstract

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Bedside calculation of stroke risk in patients with atrial fibrillation. Author(s): Sprague D, Loewen P. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 March 1; 60(5): 427-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635446&dopt=Abstract

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Behaviour of the adrenergic cardiovascular drive in atrial fibrillation and cardiac arrhythmias. Author(s): Grassi G, Seravalle G, Bertinieri G, Mancia G. Source: Acta Physiologica Scandinavica. 2003 March; 177(3): 399-404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609012&dopt=Abstract

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Beneficial effect of carvedilol on heart rate response to exercise in digitalised patients with heart failure in atrial fibrillation due to idiopathic dilated cardiomyopathy. Author(s): Agarwal AK, Venugopalan P. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2001 August; 3(4): 437-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511429&dopt=Abstract

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Benefits of prophylactic continuous infusion of furosemide after the maze procedure for atrial fibrillation. Author(s): Ad N, Suyderhoud JP, Kim YD, Makary MA, DeGroot KW, Lue HC, Pirovic EA, Duvall WZ, Cox JL. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 February; 123(2): 2326. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828281&dopt=Abstract

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Bepridil prevents paroxysmal atrial fibrillation by a class III antiarrhythmic drug effect. Author(s): Yoshida T, Niwano S, Inuo K, Saito J, Kojima J, Ikeda-Murakami K, Hara H, Izumi T. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 314-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687836&dopt=Abstract

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Biatrial multisite mapping of atrial premature complexes triggering onset of atrial fibrillation. Author(s): Schmitt C, Ndrepepa G, Weber S, Schmieder S, Weyerbrock S, Schneider M, Karch MR, Deisenhofer I, Schreieck J, Zrenner B, Schomig A. Source: The American Journal of Cardiology. 2002 June 15; 89(12): 1381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062732&dopt=Abstract

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Biatrial pacing for paroxysmal atrial fibrillation: a randomized prospective study into the suppression of paroxysmal atrial fibrillation using biatrial pacing. Author(s): Mirza I, James S, Holt P. Source: Journal of the American College of Cardiology. 2002 August 7; 40(3): 457-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142111&dopt=Abstract

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Bilateral renal arterial embolisation in a patient with mitral stenosis and atrial fibrillation: an uncommon reason of flank pain. Author(s): Yavuzgil O, Gurgun C, Zoghi M. Source: Anadolu Kardiyoloji Dergisi : Akd = the Anatolian Journal of Cardiology. 2003 March; 3(1): 73-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626316&dopt=Abstract

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Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial. Author(s): Page RL, Kerber RE, Russell JK, Trouton T, Waktare J, Gallik D, Olgin JE, Ricard P, Dalzell GW, Reddy R, Lazzara R, Lee K, Carlson M, Halperin B, Bardy GH; BiCard Investigators. Source: Journal of the American College of Cardiology. 2002 June 19; 39(12): 1956-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084594&dopt=Abstract

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Biphasic waveform cardioversion as an alternative to internal cardioversion for atrial fibrillation refractory to conventional monophasic waveform transthoracic shock. Author(s): Benditt DG, Samniah N, Iskos D, Lurie KG, Padanilam BJ, Sakaguchi S. Source: The American Journal of Cardiology. 2001 December 15; 88(12): 1426-8, A8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741567&dopt=Abstract

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Bleeding and thromboembolic risks of internal cardioversion for persistent atrial fibrillation. Author(s): Tse HF, Lau CP. Source: Pacing and Clinical Electrophysiology : Pace. 2002 December; 25(12): 1752-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520677&dopt=Abstract

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Bleeding complications in patients with atrial fibrillation undergoing cardioversion randomized to transesophageal echocardiographically guided and conventional anticoagulation therapies. Author(s): Klein AL, Murray RD, Grimm RA, Li J, Apperson-Hansen C, Jasper SE, Goodman-Bizon AS, Lieber EA, Black IW; ACUTE Investigators. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860217&dopt=Abstract

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Blockade of atrial angiotensin II type 1 receptors: a novel antiarrhythmic strategy to prevent atrial fibrillation? Author(s): Klein HU, Goette A. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2205-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821248&dopt=Abstract

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Blood flow in the left atrial appendage and embolic stroke in nonvalvular atrial fibrillation. Author(s): Takada T, Yasaka M, Nagatsuka K, Minematsu K, Yamaguchi T. Source: European Neurology. 2001; 46(3): 148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598333&dopt=Abstract

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By the way, doctor. Drugs for atrial fibrillation. I had atrial fibrillation and was zapped back into sinus rhythm several weeks ago. It seems like I'm going to have to take either aspirin or Coumadin. Which is better, and why? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2001 April; 26(6): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340029&dopt=Abstract

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Can P wave parameters obtained from 12-lead surface electrocardiogram be a predictor for atrial fibrillation in patients who have structural heart disease? Author(s): Altunkeser BB, Ozdemir K, Gok H, Temizhan A, Tokac M, Karabag T. Source: Angiology. 2003 July-August; 54(4): 475-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934768&dopt=Abstract

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Can P wave wavelet analysis predict atrial fibrillation after coronary artery bypass grafting? Author(s): Vassilikos V, Dakos G, Chouvarda I, Karagounis L, Karvounis H, Maglaveras N, Mochlas S, Spanos P, Louridas G. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 305-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687834&dopt=Abstract

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Catheter ablation of chronic atrial fibrillation with noncontact mapping: are continuous linear lesions associated with ablation success? Author(s): Seidl K, Schwacke H, Zahn R, Rameken M, Drogemuller A, Senges J. Source: Pacing and Clinical Electrophysiology : Pace. 2003 February; 26(2 Pt 1): 534-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710311&dopt=Abstract

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Catheter ablation of paroxysmal atrial fibrillation initiated by non-pulmonary vein ectopy. Author(s): Lin WS, Tai CT, Hsieh MH, Tsai CF, Lin YK, Tsao HM, Huang JL, Yu WC, Yang SP, Ding YA, Chang MS, Chen SA. Source: Circulation. 2003 July 1; 107(25): 3176-83. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821558&dopt=Abstract

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Catheter-induced linear lesions in the left atrium in patients with atrial fibrillation: an electroanatomic study. Author(s): Ernst S, Ouyang F, Lober F, Antz M, Kuck KH. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1271-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522495&dopt=Abstract

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Characteristics of rapid rhythms recorded within pulmonary veins during atrial fibrillation. Author(s): Tada H, Ozaydin M, Oral H, Knight BP, Chugh A, Scharf C, Pelosi F Jr, Strickberger SA, Morady F. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1342-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822750&dopt=Abstract

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Characterization of onset mechanism and waveform analysis in patients with atrial fibrillation using a high-resolution noncontact mapping system. Author(s): Weber S, Ndrepepa G, Schneider M, Geissler B, Schreieck J, Karch M, Schmieder S, Deisenhofer I, Zrenner B, Schomig A, Schmitt C. Source: Journal of Cardiovascular Electrophysiology. 2003 February; 14(2): 176-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693501&dopt=Abstract

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Circadian variation in ventricular tachycardia and atrial fibrillation in a medicalcardiological ICU. Author(s): Delle Karth G, Reinelt P, Buberl A, Geppert A, Huelsmann M, Berger R, Heinz G. Source: Intensive Care Medicine. 2003 June; 29(6): 963-8. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698245&dopt=Abstract

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Classifications and practice guidelines in atrial fibrillation: a changing landscape. Author(s): Saksena S. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2003 February; 8(1): 5-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652171&dopt=Abstract

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Clinical characteristics in transient ischemic attack patients with atrial fibrillation. Author(s): Kimura K, Minematsu K, Wada K, Yonemura K, Nakajima M. Source: Intern Med. 2003 March; 42(3): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705790&dopt=Abstract

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Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study. Author(s): Boriani G, Gallina M, Merlini L, Bonne G, Toniolo D, Amati S, Biffi M, Martignani C, Frabetti L, Bonvicini M, Rapezzi C, Branzi A. Source: Stroke; a Journal of Cerebral Circulation. 2003 April; 34(4): 901-8. Epub 2003 March 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649505&dopt=Abstract

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Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm. Author(s): Nao T, Ohkusa T, Hisamatsu Y, Inoue N, Matsumoto T, Yamada J, Shimizu A, Yoshiga Y, Yamagata T, Kobayashi S, Yano M, Hamano K, Matsuzaki M. Source: The American Journal of Cardiology. 2003 March 15; 91(6): 678-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633797&dopt=Abstract

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Comparison of monophasic and biphasic shocks for transthoracic cardioversion of atrial fibrillation. Author(s): Scholten M, Szili-Torok T, Klootwijk P, Jordaens L. Source: Heart (British Cardiac Society). 2003 September; 89(9): 1032-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923020&dopt=Abstract

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Comparison of prognostic value of atrial fibrillation versus sinus rhythm in patients on long-term hemodialysis. Author(s): Vazquez E, Sanchez-Perales C, Lozano C, Garcia-Cortes MJ, Borrego F, Guzman M, Perez P, Pagola C, Borrego MJ, Perez V. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 868-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516897&dopt=Abstract

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Comparison of the efficacy and safety of two biphasic defibrillator waveforms for the conversion of atrial fibrillation to sinus rhythm. Author(s): Neal S, Ngarmukos T, Lessard D, Rosenthal L. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 810-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516881&dopt=Abstract

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Competing autonomic mechanisms precede the onset of postoperative atrial fibrillation. Author(s): Amar D, Zhang H, Miodownik S, Kadish AH. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1262-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522493&dopt=Abstract

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Concomitant recovery of atrial mechanical and endocrine function after cardioversion in patients with persistent atrial fibrillation. Author(s): Wozakowska-Kaplon B, Opolski G. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1716-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767653&dopt=Abstract

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Controversies in the mechanisms and ablation of pulmonary vein atrial fibrillation. Author(s): Chen SA, Tai CT, Yeh HI, Chen YJ, Lin CI. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822745&dopt=Abstract

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Current clinical issues in atrial fibrillation. Author(s): Chung MK. Source: Cleve Clin J Med. 2003 July; 70 Suppl 3: S6-11. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882403&dopt=Abstract

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Cycle length-dependent repolarization changes during atrial fibrillation in the Brugada syndrome. Author(s): Marquez MF, Medrano G, Frank R, Fontaine G, Hermosillo AG, Cardenas M. Source: Journal of Electrocardiology. 2003 April; 36(2): 161-4; Discussion 165. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764699&dopt=Abstract

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D-dimer determination as a screening tool to exclude atrial thrombi in atrial fibrillation. Author(s): Somloi M, Tomcsanyi J, Nagy E, Bodo I, Bezzegh A. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 85-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842257&dopt=Abstract

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Delayed cure despite early recurrence after pulmonary vein isolation for atrial fibrillation. Author(s): O'Donnell D, Furniss SS, Dunuwille A, Bourke JP. Source: The American Journal of Cardiology. 2003 January 1; 91(1): 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505579&dopt=Abstract

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Determinants of persistent atrial fibrillation in patients with DDD pacemaker implantation. Author(s): Demir AD, Soylu M, Ozdemir O, Balbay Y, Topaloglu S, Sasmaz A, Korkmaz S. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 719-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698672&dopt=Abstract

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Determination of the target ventricular rate in patients with atrial fibrillation by evaluation of ventriculoarterial coupling. Author(s): Nobuoka S, Hatano S, Nagashima J, Yoshida A, Adachi H, Imai Y, Shibamoto M, Ikeda K, Miyake F. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2002; 29(2): 100-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075864&dopt=Abstract

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Development and description of a decision analysis based decision support tool for stroke prevention in atrial fibrillation. Author(s): Thomson R, Robinson A, Greenaway J, Lowe P; DARTS Team. Source: Quality & Safety in Health Care. 2002 March; 11(1): 25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078365&dopt=Abstract

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Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. Author(s): Devereaux PJ, Anderson DR, Gardner MJ, Putnam W, Flowerdew GJ, Brownell BF, Nagpal S, Cox JL. Source: Bmj (Clinical Research Ed.). 2001 November 24; 323(7323): 1218-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719412&dopt=Abstract

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Differences in heart rate dynamics before the spontaneous onset of long and short episodes of paroxysmal atrial fibrillation. Author(s): Vikman S, Yli-Mayry S, Makikallio TH, Airaksinen KE, Huikuri HV. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2001 April; 6(2): 134-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11333171&dopt=Abstract

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Differences in sympathetic and vagal effects on paroxysmal atrial fibrillation: a simulation study. Author(s): Ashihara T, Yao T, Namba T, Kawase A, Ikeda T, Nakazawa K, Ito M. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2002; 56 Suppl 2: 359S-363S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653194&dopt=Abstract

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Differences in the morphology and duration between premature P waves and the preceding sinus complexes in patients with a history of paroxysmal atrial fibrillation. Author(s): Dilaveris PE, Pantazis A, Zervopoulos G, Kallikazaros J, Stefanadis C, Toutouzas PK. Source: Clin Cardiol. 2003 July; 26(7): 341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862301&dopt=Abstract

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Dilatation of the pulmonary veins in atrial fibrillation: a transesophageal echocardiographic evaluation. Author(s): Knackstedt C, Visser L, Plisiene J, Zarse M, Waldmann M, Mischke K, Koch KC, Hoffmann R, Franke A, Hanrath P, Schauerte P. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1371-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822754&dopt=Abstract

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Dissociated activity and pulmonary vein fibrillation following functional disconnection: impact for the arrhythmogenesis of focal atrial fibrillation. Author(s): Willems S, Weiss C, Risius T, Rostock T, Hoffmann M, Ventura R, Meinertz T. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1363-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822753&dopt=Abstract

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Diurnal and seasonal variation of stroke incidence in patients with cardioembolic stroke due to atrial fibrillation. Author(s): Spengos K, Vemmos K, Tsivgoulis G, Manios E, Zakopoulos N, Mavrikakis M, Vassilopoulos D. Source: Neuroepidemiology. 2003 May-June; 22(3): 204-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711853&dopt=Abstract

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Does short-term anticoagulation with heparin increase risk for microemboli patients undergoing transesophageal guided electrical cardioversion for atrial fibrillation? A transcranial Doppler ultrasonography study. Author(s): Gokterin O, Uzener N, Ata N, Kudaiberdieva G, Gucuyener D, Ozdemir G, Timuralp B. Source: International Journal of Cardiology. 2003 March; 88(1): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659996&dopt=Abstract

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Dofetilide (Tikosyn): a new drug to control atrial fibrillation. Author(s): Saliba WI. Source: Cleve Clin J Med. 2001 April; 68(4): 353-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11326815&dopt=Abstract

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Dofetilide and atrial fibrillation. Author(s): Benson LM, Powless D. Source: The American Journal of Nursing. 2003 February; 103(2): 64Aa-64Cc, 64Ee-64Gg. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582342&dopt=Abstract

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Doppler transmitral flow indexes and risk of atrial fibrillation (the Framingham Heart Study). Author(s): Vasan RS, Larson MG, Levy D, Galderisi M, Wolf PA, Benjamin EJ; National Heart, Lung, and Blood Institute, National Institutes of Health. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1079-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714150&dopt=Abstract

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Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Author(s): Touboul P, Brugada J, Capucci A, Crijns HJ, Edvardsson N, Hohnloser SH. Source: European Heart Journal. 2003 August; 24(16): 1481-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919771&dopt=Abstract

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Drop in plasma brain natriuretic peptide levels after successful direct current cardioversion in chronic atrial fibrillation. Author(s): Ohta Y, Shimada T, Yoshitomi H, Inoue S, Murakami Y, Shimizu H, Nakamura K, Ohta T, Katoh H, Ishibashi Y. Source: The Canadian Journal of Cardiology. 2001 April; 17(4): 415-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11329541&dopt=Abstract

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Duration of warfarin sodium therapy prior to electrical cardioversion of atrial fibrillation. Author(s): Ryman J, Frick M, Frykman V, Rosenqvist M. Source: Journal of Internal Medicine. 2003 January; 253(1): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588539&dopt=Abstract

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Dynamic alterations in right atrial activation during atrial fibrillation. Author(s): O'Donnell D, Furniss SS, Bourke JP. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2003 February; 8(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652175&dopt=Abstract

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Effect of amiodarone on dispersion of atrial refractoriness and cycle length in patients with atrial fibrillation. Author(s): Fynn SP, Todd DM, Hobbs WJ, Armstrong KL, Fitzpatrick AP, Garratt CJ. Source: Journal of Cardiovascular Electrophysiology. 2003 May; 14(5): 485-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776865&dopt=Abstract

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Effect of atrial fibrillation and an irregular ventricular response on sympathetic nerve activity in human subjects. Author(s): Wasmund SL, Li JM, Page RL, Joglar JA, Kowal RC, Smith ML, Hamdan MH. Source: Circulation. 2003 April 22; 107(15): 2011-5. Epub 2003 Apr 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681998&dopt=Abstract

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Effect of atrial fibrillation duration on probability of immediate recurrence after transthoracic cardioversion. Author(s): Oral H, Ozaydin M, Sticherling C, Tada H, Scharf C, Chugh A, Lai SW, Pelosi F Jr, Knight BP, Strickberger SA, Morady F. Source: Journal of Cardiovascular Electrophysiology. 2003 February; 14(2): 182-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693502&dopt=Abstract

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Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. Author(s): Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, Singer DE. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1019-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968085&dopt=Abstract

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Effect of right atrial pacing, intravenous amiodarone and beta blockers for suppression of atrial fibrillation after coronary artery bypass surgery: a pilot study. Author(s): Cardona F, Seide H, Cox RA, Perez CM. Source: P R Health Sci J. 2003 June; 22(2): 119-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866134&dopt=Abstract

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Effectiveness and costs of chemical versus electrical cardioversion of atrial fibrillation. Author(s): de Paola AA, Figueiredo E, Sesso R, Veloso HH, Nascimento LO; SOCES Investigators. Source: International Journal of Cardiology. 2003 April; 88(2-3): 157-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714194&dopt=Abstract

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Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: a meta-analysis. Author(s): Letelier LM, Udol K, Ena J, Weaver B, Guyatt GH. Source: Archives of Internal Medicine. 2003 April 14; 163(7): 777-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695268&dopt=Abstract

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Effects of lisinopril in patients with heart failure and chronic atrial fibrillation. Author(s): Van Den Berg MP, Crijns HJ, Van Veldhuisen DJ, Griep N, De Kam PJ, Lie KI. Source: Journal of Cardiac Failure. 1995 December; 1(5): 355-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836710&dopt=Abstract

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Effects of low-dose warfarin and aspirin versus no treatment on stroke in a mediumrisk patient population with atrial fibrillation. Author(s): Edvardsson N, Juul-Moller S, Omblus R, Pehrsson K. Source: Journal of Internal Medicine. 2003 July; 254(1): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823646&dopt=Abstract

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Effects of operator experience on the outcome and duration of pulmonary vein isolation procedures for atrial fibrillation. Author(s): Knight BP, Oral H, Chugh A, Scharf C, Lai SW, Pelosi F Jr, Strickberger SA, Morady F. Source: The American Journal of Cardiology. 2003 March 15; 91(6): 673-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633796&dopt=Abstract

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Efficacy of antithrombotic therapy for atrial fibrillation in the oldest old. Author(s): Fisher A, Davis M. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 887-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757587&dopt=Abstract

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Electrical cardioversion for atrial fibrillation and flutter. Author(s): Mead GE, Flapan AD, Elder AT. Source: Cochrane Database Syst Rev. 2002; (1): Cd002903. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869642&dopt=Abstract

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Electrical disconnection versus anatomical isolation of the pulmonary veins: two sides of the same treatment for atrial fibrillation? Author(s): Adragao P, Reis-Santos K, Scanavacca M, Cavaco D, Aguiar C, Morgado F, Ribeiras R, Bernardo R, Bonhorst D, Seabra-Gomes R. Source: Rev Port Cardiol. 2003 June; 22(6): 777-87. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526695&dopt=Abstract

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Electrocardiographic and electrophysiological characteristics of atrial fibrillation organized into atrial flutter by oral administration of class I antiarrhythmic agents. Author(s): Ohmura K, Kobayashi Y, Miyauchi Y, Endoh Y, Atarashi H, Katoh T, Takano T. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 692-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698669&dopt=Abstract

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Electrophysiologically guided pulmonary vein isolation during sustained atrial fibrillation. Author(s): Macle L, Jais P, Scavee C, Weerasooriya R, Shah DC, Hocini M, Choi KJ, Raybaud F, Clementy J, Haissaguerre M. Source: Journal of Cardiovascular Electrophysiology. 2003 March; 14(3): 255-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716106&dopt=Abstract

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Emergency department-based atrial fibrillation treatment strategy with lowmolecular-weight heparin. Author(s): Wakai A. Source: Annals of Emergency Medicine. 2003 May; 41(5): 757-8; Author Reply 758-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744251&dopt=Abstract

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Emergency management of atrial fibrillation. Author(s): Wakai A, O'Neill JO. Source: Postgraduate Medical Journal. 2003 June; 79(932): 313-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840118&dopt=Abstract

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Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials. Author(s): Vermes E, Tardif JC, Bourassa MG, Racine N, Levesque S, White M, Guerra PG, Ducharme A. Source: Circulation. 2003 June 17; 107(23): 2926-31. Epub 2003 May 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771010&dopt=Abstract

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Evolution of non-pharmacological curative therapy for atrial fibrillation. Where do we stand today? Author(s): Pappone C, Rosanio S. Source: International Journal of Cardiology. 2003 April; 88(2-3): 135-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714191&dopt=Abstract

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Extraction of physiological and clinical information from intra-atrial electrograms during atrial fibrillation: review of methods. Author(s): Barbaro V, Bartolini P, Calcagnini G, Censi F. Source: Ann Ist Super Sanita. 2001; 37(3): 319-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889947&dopt=Abstract

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Factor V Leiden mutation and its relation to left atrial thrombus in chronic nonrheumatic atrial fibrillation. Author(s): Gokce M, Ucar F, Kucukosmanoglu M, Erdogan T, Kaplan S. Source: Japanese Heart Journal. 2003 July; 44(4): 481-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906030&dopt=Abstract

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Factors associated with early atrial fibrillation after ablation of common atrial flutter. A single centre prospective study. Author(s): Da Costa A, Romeyer C, Mourot S, Messier M, Cerisier A, Faure E, Isaaz K. Source: European Heart Journal. 2002 March; 23(6): 498-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863353&dopt=Abstract

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Factors associated with the development of atrial fibrillation in COPD patients: the role of P-wave dispersion. Author(s): Tukek T, Yildiz P, Akkaya V, Karan MA, Atilgan D, Yilmaz V, Korkut F. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2002 July; 7(3): 222-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167183&dopt=Abstract

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Factors influencing physicians' reported use of anticoagulation therapy in nonvalvular atrial fibrillation: a cross-sectional survey. Author(s): Gross CP, Vogel EW, Dhond AJ, Marple CB, Edwards RA, Hauch O, Demers EA, Ezekowitz M. Source: Clinical Therapeutics. 2003 June; 25(6): 1750-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860496&dopt=Abstract

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Factors predicting success rate and recurrence of atrial fibrillation after first electrical cardioversion in patients with persistent atrial fibrillation. Author(s): Frick M, Frykman V, Jensen-Urstad M, Ostergren J, Rosenqvist M. Source: Clin Cardiol. 2001 March; 24(3): 238-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11288971&dopt=Abstract

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Familial atrial fibrillation is a genetically heterogeneous disorder. Author(s): Darbar D, Herron KJ, Ballew JD, Jahangir A, Gersh BJ, Shen WK, Hammill SC, Packer DL, Olson TM. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821245&dopt=Abstract

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Feasibility of predicting the risk of atrial fibrillation after coronary artery bypass surgery with logistic regression model. Author(s): Hakala T, Pitkanen O, Hippelainen M. Source: Scand J Surg. 2002; 91(4): 339-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558083&dopt=Abstract

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Feasibility of pulmonary vein ostia radiofrequency ablation in patients with atrial fibrillation: a multicenter study (CACAF pilot study). Author(s): Stabile G, Bertaglia E, Senatore G, de Simone A, Zerbo F, Carreras G, Turco P, Pascotto P, Fazzari M. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 284-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687829&dopt=Abstract

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Fibrin D-dimer levels in atrial fibrillation as an index of thrombogenesis: a possible test to exclude left atrial thrombus? Author(s): Tayebjee MH, Lip GY. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 47-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842244&dopt=Abstract

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Findings suggest revised atrial fibrillation approach. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2003 January 10; 14(1): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762304&dopt=Abstract

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Five-year mortality in men and women with atrial fibrillation. Author(s): Wandell PE. Source: Scandinavian Journal of Primary Health Care. 2001 June; 19(2): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11482411&dopt=Abstract

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Focal atrial fibrillation: A four-headed Lernaean hydra? Author(s): Delacretaz E. Source: Journal of Cardiovascular Electrophysiology. 2002 February; 13(2): 189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900297&dopt=Abstract

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Frequency of anticoagulation for atrial fibrillation and reasons for its non-use at a Veterans Affairs medical center. Author(s): Bradley BC, Perdue KS, Tisdel KA, Gilligan DM. Source: The American Journal of Cardiology. 2000 March 1; 85(5): 568-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11078269&dopt=Abstract

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Frequency of symptomatic atrial fibrillation in patients enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Author(s): Epstein AE, Vidaillet H, Greene HL, Curtis AB, Ellenbogen KA, Simmons T, Mickel M. Source: Journal of Cardiovascular Electrophysiology. 2002 July; 13(7): 667-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139289&dopt=Abstract

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Frequent and prolonged asymptomatic episodes of paroxysmal atrial fibrillation revealed by automatic long-term event recorders in patients with a negative 24-hour Holter. Author(s): Roche F, Gaspoz JM, Da Costa A, Isaaz K, Duverney D, Pichot V, Costes F, Lacour JR, Barthelemy JC. Source: Pacing and Clinical Electrophysiology : Pace. 2002 November; 25(11): 1587-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494616&dopt=Abstract

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Frequent atrial premature contractions as a surrogate marker for paroxysmal atrial fibrillation in patients with acute ischaemic stroke. Author(s): Wallmann D, Tuller D, Kucher N, Fuhrer J, Arnold M, Delacretaz E. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1247-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975433&dopt=Abstract

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Functional disconnection of arrhythmogenic pulmonary veins in patients with paroxysmal atrial fibrillation guided by combined electroanatomical (CARTO) and conventional mapping. Author(s): Weiss C, Willems S, Risius T, Hoffmann M, Ventura R, Meinertz T. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2002 July; 6(3): 267-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154329&dopt=Abstract

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Further evidence of localized posterior interatrial conduction delay in lone paroxysmal atrial fibrillation. Author(s): Platonov PG, Yuan S, Hertervig E, Kongstad O, Roijer A, Vygovsky AB, Chireikin LV, Olsson SB. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2001 April; 3(2): 100-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11333046&dopt=Abstract

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Gender and age differences in induced atrial fibrillation. Author(s): Tada H, Sticherling C, Chough SP, Baker RL, Wasmer K, Daoud EG, Oral H, Pelosi F Jr, Knight BP, Strickberger SA, Morady F. Source: The American Journal of Cardiology. 2001 August 15; 88(4): 436-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545773&dopt=Abstract

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Genomic medicine and atrial fibrillation. Author(s): Mestroni L. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2193-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821246&dopt=Abstract

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Getting to the heart of atrial fibrillation. Author(s): Yee CA, Rozewicz B. Source: Nursing Management. 2003 September; 34(9): 21-7; Quiz 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501528&dopt=Abstract

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Giant multiperforated atrial septal aneurysm in a patient with paroxysmal atrial fibrillation. Author(s): De Ridder S, Cramer MJ, Ernst JM, Jaarsma W. Source: European Journal of Echocardiography : the Journal of the Working Group on Echocardiography of the European Society of Cardiology. 2003 June; 4(2): 154-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749879&dopt=Abstract

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Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a biatrial basket mapping study. Author(s): Lin JL, Lai LP, Tseng YZ, Lien WP, Huang SK. Source: Journal of the American College of Cardiology. 2001 March 1; 37(3): 904-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693769&dopt=Abstract

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Heart failure complicated by atrial fibrillation: mechanistic, prognostic, and therapeutic implications. Author(s): Gronefeld GC, Hohnloser SH. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 June; 8(2): 10713. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808483&dopt=Abstract

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Heart rate variability and recurrence of atrial fibrillation after electrical cardioversion. Author(s): Ann Intern Med. 2003 Apr 15;138(8):1 Source: Annals of Medicine. 2003; 35(1): 36-42. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12693916

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Heart-brain relationship: atrial fibrillation and stroke. Author(s): Bornstein N, Corea F, Galllai V, Parnetti L. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2002 OctoberNovember; 24(7-8): 493-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450224&dopt=Abstract

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Hemodynamic effects of alternative atrial pacing sites in patients with paroxysmal atrial fibrillation. Author(s): Dabrowska-Kugacka A, Lewicka-Nowak E, Kutarski A, Zagozdzon P, Swiatecka G. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 278-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687828&dopt=Abstract

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Atrial Fibrillation

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High accuracy of automatic detection of atrial fibrillation using wavelet transform of heart rate intervals. Author(s): Duverney D, Gaspoz JM, Pichot V, Roche F, Brion R, Antoniadis A, Barthelemy JC. Source: Pacing and Clinical Electrophysiology : Pace. 2002 April; 25(4 Pt 1): 457-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991371&dopt=Abstract

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High incidence of focal atrial fibrillation (AF) from the right atrium (RA). Author(s): Chen SA, Lee SH, Tai CT, Yu WC. Source: Journal of Cardiovascular Electrophysiology. 2001 January; 12(1): 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204076&dopt=Abstract

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High plasma brain natriuretic peptide level in thromboembolism patients associated with nonvalvular atrial fibrillation: cause or effect? Author(s): Fukui S, Otani N, Katoh H, Nawashiro H, Shima K. Source: Stroke; a Journal of Cerebral Circulation. 2002 August; 33(8): 1943-4; Author Reply 1943-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154238&dopt=Abstract

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High plasma brain natriuretic polypeptide level as a marker of risk for thromboembolism in patients with nonvalvular atrial fibrillation. Author(s): Shimizu H, Murakami Y, Inoue S, Ohta Y, Nakamura K, Katoh H, Sakne T, Takahashi N, Ohata S, Sugamori T, Ishibashi Y, Shimada T. Source: Stroke; a Journal of Cerebral Circulation. 2002 April; 33(4): 1005-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11935052&dopt=Abstract

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Histologic atrial myolysis is associated with atrial fibrillation after cardiac operation. Author(s): Ad N, Snir E, Vidne BA, Golomb E. Source: The Annals of Thoracic Surgery. 2001 September; 72(3): 688-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11565642&dopt=Abstract

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Homocysteine and the risk of stroke and thromboembolism in atrial fibrillation: an uncertain role. Author(s): Nadar S, Lip GY. Source: Stroke; a Journal of Cerebral Circulation. 2003 September; 34(9): E143; Author Reply E143-5. Epub 2003 August 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933971&dopt=Abstract

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Hospitalizations for atrial fibrillation in the general male population: morbidity and risk factors. Author(s): Wilhelmsen L, Rosengren A, Lappas G. Source: Journal of Internal Medicine. 2001 November; 250(5): 382-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887972&dopt=Abstract

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Hospitalized atrial fibrillation after renal transplantation in the United States. Author(s): Abbott KC, Reynolds JC, Taylor AJ, Agodoa LY. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 April; 3(4): 471-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694071&dopt=Abstract

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How can epidemiological studies help us to prevent stroke? The example of atrial fibrillation. Author(s): Thomson R. Source: Age and Ageing. 2002 November; 31 Suppl 3: 9-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450922&dopt=Abstract

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How patients with atrial fibrillation value different health outcomes: a standard gamble study. Author(s): Robinson A, Thomson R, Parkin D, Sudlow M, Eccles M. Source: Journal of Health Services Research & Policy. 2001 April; 6(2): 92-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357250&dopt=Abstract

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How to enhance acute outcome of electrical cardioversion by drug therapy: importance of immediate reinitiation of atrial fibrillation. Author(s): Van Noord T, Van Gelder IC, Crijns HJ. Source: Journal of Cardiovascular Electrophysiology. 2002 August; 13(8): 822-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212706&dopt=Abstract

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Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation. Author(s): Dobrev D, Wettwer E, Kortner A, Knaut M, Schuler S, Ravens U. Source: Cardiovascular Research. 2002 May; 54(2): 397-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062344&dopt=Abstract

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Hybrid therapy of atrial fibrillation. Author(s): Santini M, Pignalberi C, Ricci R, Calo L. Source: Ital Heart J. 2002 October; 3(10): 571-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478814&dopt=Abstract

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Hyperhomocysteinemia is associated with the presence of left atrial thrombus in stroke patients with nonvalvular atrial fibrillation. Author(s): Ay H, Arsava EM, Tokgozoglu SL, Ozer N, Saribas O. Source: Stroke; a Journal of Cerebral Circulation. 2003 April; 34(4): 909-12. Epub 2003 February 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624219&dopt=Abstract

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Atrial Fibrillation

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Hyperthyroidism and the management of atrial fibrillation. Author(s): Shimizu T, Koide S, Noh JY, Sugino K, Ito K, Nakazawa H. Source: Thyroid : Official Journal of the American Thyroid Association. 2002 June; 12(6): 489-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165111&dopt=Abstract

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Hypertrophic cardiomyopathy in the elderly: significance of atrial fibrillation. Author(s): Doi Y, Kitaoka H. Source: J Cardiol. 2001; 37 Suppl 1: 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11433817&dopt=Abstract

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Ibutilide for pharmacological cardioversion of atrial fibrillation and flutter: impact of race on efficacy and safety. Author(s): Gowda RM, Punukollu G, Khan IA, Wilbur SL, Vasavada BC, Sacchi TJ. Source: American Journal of Therapeutics. 2003 July-August; 10(4): 259-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845389&dopt=Abstract

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Ibutilide versus amiodarone in atrial fibrillation: a double-blinded, randomized study. Author(s): Bernard EO, Schmid ER, Schmidlin D, Scharf C, Candinas R, Germann R. Source: Critical Care Medicine. 2003 April; 31(4): 1031-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682468&dopt=Abstract

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Images in cardiovascular medicine. Pulmonary vein stenosis after radiofrequency ablation for atrial fibrillation: image findings with multiphasic pulmonary magnetic resonance angiography. Author(s): Fink C, Schmaehl A, Bock M, Tuengerthal S, Delorme S. Source: Circulation. 2003 May 20; 107(19): E129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756194&dopt=Abstract

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Impact of atrial fibrillation on the voltage of bipolar signals acquired from the left and right atria. Author(s): Ndrepepa G, Schneider MA, Karch MR, Weber S, Schreieck J, Zrenner B, Schmitt C. Source: Pacing and Clinical Electrophysiology : Pace. 2003 April; 26(4 Pt 1): 862-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715847&dopt=Abstract

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Impact of rate versus rhythm control on quality of life in patients with persistent atrial fibrillation. Results from a prospective randomized study. Author(s): Gronefeld GC, Lilienthal J, Kuck KH, Hohnloser SH; Pharmacological Intervention in Atrial Fibrillation (PIAF) Study investigators. Source: European Heart Journal. 2003 August; 24(15): 1430-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909072&dopt=Abstract

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Inappropriate use of atrioventricular nodal vagal stimulation in atrial fibrillation. Author(s): Krohn BG. Source: Circulation. 2003 April 8; 107(13): E90; Author Reply E90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682036&dopt=Abstract

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Incidence and clinical consequences of atrial fibrillation within 1 year of first-time isolated coronary bypass surgery. Author(s): Elahi M, Hadjinikolaou L, Galinanes M. Source: Circulation. 2003 September 9; 108 Suppl 1: Ii207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970234&dopt=Abstract

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Incidence of pulmonary vein stenosis 2 years after radiofrequency catheter ablation of refractory atrial fibrillation. Author(s): Arentz T, Jander N, von Rosenthal J, Blum T, Furmaier R, Gornandt L, Josef Neumann F, Kalusche D. Source: European Heart Journal. 2003 May; 24(10): 963-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714028&dopt=Abstract

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Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation. role of phosphatase 2A. Author(s): Klein G, Schroder F, Vogler D, Schaefer A, Haverich A, Schieffer B, Korte T, Drexler H. Source: Cardiovascular Research. 2003 July 1; 59(1): 37-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829174&dopt=Abstract

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Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention. Author(s): Wattigney WA, Mensah GA, Croft JB. Source: Circulation. 2003 August 12; 108(6): 711-6. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885749&dopt=Abstract

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Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation. Author(s): Roldan V, Marin F, Blann AD, Garcia A, Marco P, Sogorb F, Lip GY. Source: European Heart Journal. 2003 July; 24(14): 1373-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871695&dopt=Abstract

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International consensus on nomenclature and classification of atrial fibrillation: A collaborative project of the Working Group on Arrhythmias and the Working Group of Cardiac Pacing of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Author(s): Levy S, Camm AJ, Saksena S, Aliot E, Breithardt G, Crijns HJ, Davies DW, Kay GN, Prystowsky EN, Sutton R, Waldo AL, Wyse DG; Working Group on Arrhythmias of European Society of Cardiology; Working Group of Cardiac Pacing of European Society of Cardiology; North American Society of Pacing and Electrophysiology. Source: Journal of Cardiovascular Electrophysiology. 2003 April; 14(4): 443-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741724&dopt=Abstract

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International consensus on nomenclature and classification of atrial fibrillation; a collaborative project of the Working Group on Arrhythmias and the Working Group on Cardiac Pacing of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Author(s): Levy S, Camm AJ, Saksena S, Aliot E, Breithardt G, Crijns H, Davies W, Kay N, Prystowsky E, Sutton R, Waldo A, Wyse DG; Working Group on Arrhythmias, Working Group on Cardiac Pacing of the European Society of Cardiology, North American Society of Pacing and Electrophysiology. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 April; 5(2): 119-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633634&dopt=Abstract

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Intracardiac low-energy versus transthoracic high-energy direct-current cardioversion of atrial fibrillation: a randomised comparison. Author(s): Friberg J, Gadsboll N. Source: Cardiology. 2003; 99(2): 72-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711881&dopt=Abstract

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Intraoperative high-rate atrial pacing test as a predictor of atrial fibrillation after coronary artery bypass surgery. Author(s): Hakala T, Berg E, Hartikainen JE, Hippelainen MJ. Source: The Annals of Thoracic Surgery. 2002 December; 74(6): 2072-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643397&dopt=Abstract

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Intravenous amiodarone for cardioversion of recent-onset atrial fibrillation. Author(s): Cybulski J, Kulakowski P, Budaj A, Danielewicz H, Maciejewicz J, KawkaUrbanek T, Ceremuzynski L. Source: Clin Cardiol. 2003 July; 26(7): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862299&dopt=Abstract

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Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: the Atrial Fibrillation Suppression Trial II (AFIST II). Author(s): White CM, Caron MF, Kalus JS, Rose H, Song J, Reddy P, Gallagher R, Kluger J; Atrial Fibrillation Suppression Trial II. Source: Circulation. 2003 September 9; 108 Suppl 1: Ii200-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970233&dopt=Abstract

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Intravenously administered digoxin in patients with acute atrial fibrillation: a population pharmacokinetic/pharmacodynamic analysis based on the Digitalis in Acute Atrial Fibrillation trial. Author(s): Hornestam B, Jerling M, Karlsson MO, Held P; DAAf Trial Group. Source: European Journal of Clinical Pharmacology. 2003 March; 58(11): 747-55. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634981&dopt=Abstract

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Is it time to choose amiodarone for postoperative atrial fibrillation? Author(s): Saltman AE. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1202-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830035&dopt=Abstract

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Is pulmonary vein isolation necessary for curing atrial fibrillation? Author(s): Stabile G, Turco P, La Rocca V, Nocerino P, Stabile E, De Simone A. Source: Circulation. 2003 August 12; 108(6): 657-60. Epub 2003 Aug 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900336&dopt=Abstract

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JAMA patient page. Atrial fibrillation. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2003 August 27; 290(8): 1118. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941685&dopt=Abstract

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Just another case of atrial fibrillation? Author(s): Varma N, Suryaprasad A, Cosio FG. Source: Pacing and Clinical Electrophysiology : Pace. 2002 March; 25(3): 358-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990666&dopt=Abstract

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KCNQ1 gain-of-function mutation in familial atrial fibrillation. Author(s): Chen YH, Xu SJ, Bendahhou S, Wang XL, Wang Y, Xu WY, Jin HW, Sun H, Su XY, Zhuang QN, Yang YQ, Li YB, Liu Y, Xu HJ, Li XF, Ma N, Mou CP, Chen Z, Barhanin J, Huang W. Source: Science. 2003 January 10; 299(5604): 251-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522251&dopt=Abstract

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Lasso catheter guided ablation for paroxysmal atrial fibrillation: the first experience in Thailand. Author(s): Raungratanaamporn O, Bhurippanyo K, Chotinaiwattarakul C, Suksap S, Chirapastan A, Ninmaneechot N, Numee M. Source: J Med Assoc Thai. 2003 May; 86 Suppl 1: S96-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866775&dopt=Abstract

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Late improvement in ventricular performance following internal cardioversion for persistent atrial fibrillation: an argument in support of concealed cardiomyopathy. Author(s): Boriani G, Biffi M, Rapezzi C, Ferlito M, Bronzetti G, Bacchi L, Zannoli R, Branzi A. Source: Pacing and Clinical Electrophysiology : Pace. 2003 May; 26(5): 1218-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765450&dopt=Abstract

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Left atrial appendage function and pulmonary venous flow in patients with nonrheumatic atrial fibrillation and their relation to spontaneous echo contrast. Author(s): Bollmann A, Binias KH, Grothues F, Schwerdtfeger A, Klein HU. Source: Echocardiography (Mount Kisco, N.Y.). 2002 January; 19(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11884253&dopt=Abstract

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Left atrial flutter after radiofrequency catheter ablation of focal atrial fibrillation. Author(s): Villacastin J, Perez-Castellano N, Moreno J, Gonzalez R. Source: Journal of Cardiovascular Electrophysiology. 2003 April; 14(4): 417-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741717&dopt=Abstract

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Left atrial size after cardioversion for atrial fibrillation: effect of external direct current shock. Author(s): Mattioli AV, Bonatti S, Bonetti L, Mattioli G. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 March; 16(3): 271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618736&dopt=Abstract

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Left atrial size and function after spontaneous cardioversion of atrial fibrillation and their relation to N-terminal atrial natriuretic peptide. Author(s): Mattioli AV, Bonatti S, Bonetti L, Borella P, Mattioli G. Source: The American Journal of Cardiology. 2003 June 15; 91(12): 1478-81, A8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804740&dopt=Abstract

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Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation. Author(s): Stoddard MF, Singh P, Dawn B, Longaker RA. Source: American Heart Journal. 2003 April; 145(4): 676-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679765&dopt=Abstract

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Left atrial thrombus, transient ischemic attack, and atrial fibrillation: does left atrial thrombus predict? Does absence protect? Author(s): Sheahan RG. Source: American Heart Journal. 2003 April; 145(4): 582-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679752&dopt=Abstract

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Left ventricular performance during acute rate control in atrial fibrillation: the importance of heart rate and agent used. Author(s): Pinter A, Dorian P, Paquette M, Ng A, Burns M, Spanu I, Freeman M, Korley V, Newman D. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 March; 8(1): 1724. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652326&dopt=Abstract

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Left ventricular relaxation abnormality is detectable by analysis of the relaxation time constant in patients with atrial fibrillation. Author(s): Harada K, Sugishita Y, Shimizu T, Yao A, Matsui H, Kohmoto O, Serizawa T, Nagai R, Takahashi T. Source: Japanese Circulation Journal. 2001 July; 65(7): 610-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450688&dopt=Abstract

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Lessons from the Stroke Prevention in Atrial Fibrillation trials. Author(s): Hart RG, Halperin JL, Pearce LA, Anderson DC, Kronmal RA, McBride R, Nasco E, Sherman DG, Talbert RL, Marler JR; Stroke Prevention in Atrial Fibrillation Investigators. Source: Annals of Internal Medicine. 2003 May 20; 138(10): 831-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755555&dopt=Abstract

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Linear ablation for atrial fibrillation: have we come full circle?. Author(s): Wilber DJ. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1283-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522496&dopt=Abstract

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Locus for atrial fibrillation maps to chromosome 6q14-16. Author(s): Ellinor PT, Shin JT, Moore RK, Yoerger DM, MacRae CA. Source: Circulation. 2003 June 17; 107(23): 2880-3. Epub 2003 Jun 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782570&dopt=Abstract

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Lone atrial fibrillation during pregnancy. Author(s): Gowda RM, Punukollu G, Khan IA, Wilbur SL, Navarro VS, Vasavada BC, Sacchi TJ. Source: International Journal of Cardiology. 2003 March; 88(1): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660001&dopt=Abstract

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Long term warfarin associated with bilateral blindness in a patient with atrial fibrillation and macular degeneration. Author(s): Ung T, James M, Gray RH. Source: Heart (British Cardiac Society). 2003 September; 89(9): 985. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923003&dopt=Abstract

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Long-term management of atrial fibrillation: rhythm or rate control? Author(s): Kovacs KA. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 March 4; 168(5): 591-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615758&dopt=Abstract

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Long-term outcome after stroke due to atrial fibrillation. Author(s): Mattle HP. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16 Suppl 1: 3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698012&dopt=Abstract

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Low incidence of hemorrhagic complications of oral anticoagulant therapy in patients with atrial fibrillation in the daily practice of an anticoagulation clinic. Author(s): Poli D, Antonucci E, Lombardi A, Cecchi E, Corsini I, Gensini GF, Abbate R, Prisco D. Source: Ital Heart J. 2003 January; 4(1): 44-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690920&dopt=Abstract

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Low-dose oral amiodarone prophylaxis reduces atrial fibrillation after pulmonary resection. Author(s): Lanza LA, Visbal AI, DeValeria PA, Zinsmeister AR, Diehl NN, Trastek VF. Source: The Annals of Thoracic Surgery. 2003 January; 75(1): 223-30; Discussion 230. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537220&dopt=Abstract

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Low-energy cardioversion versus medical treatment for the termination of atrial fibrillation after CABG. Author(s): Bechtel JF, Christiansen JF, Sievers HH, Bartels C. Source: The Annals of Thoracic Surgery. 2003 April; 75(4): 1185-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683560&dopt=Abstract

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Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. Author(s): AFFIRM First Antiarrhythmic Drug Substudy Investigators. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 20-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849654&dopt=Abstract

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Management of atrial fibrillation in older patients. Author(s): Khan SA, Ghosh P. Source: J Pak Med Assoc. 2002 December; 52(12): 566-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627906&dopt=Abstract

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Management of atrial fibrillation in the emergency department. Author(s): Crozier I, Melton I, Pearson S. Source: Internal Medicine Journal. 2003 April; 33(4): 182-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680985&dopt=Abstract

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Managing atrial fibrillation--redrawing a line in the sand. Author(s): Kilborn MJ. Source: The Medical Journal of Australia. 2003 May 19; 178(10): 480-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741931&dopt=Abstract

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Managing chronic atrial fibrillation: strategies to control symptoms and prevent embolism. Author(s): Martin DO. Source: Cleve Clin J Med. 2003 July; 70 Suppl 3: S30-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882405&dopt=Abstract

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Mapping atrial fibrillation. Uncertainty despite resolution. Author(s): Cain ME, Faddis MN. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 361-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875776&dopt=Abstract

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Markers of inflammation in atrial fibrillation. Author(s): Rosa A, Diurni V, Placido A, Bertazzoni G. Source: Acta Cardiol. 2003 February; 58(1): 43-4; Author Reply 44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625496&dopt=Abstract

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Measures of organization during atrial fibrillation. Author(s): Sih HJ. Source: Ann Ist Super Sanita. 2001; 37(3): 361-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889952&dopt=Abstract

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Mechanisms of onset of atrial fibrillation: a multicenter, prospective, pacemakerbased study. Author(s): Guyomar Y, Thomas O, Marquie C, Jarwe M, Klug D, Kacet S, Carlioz R, Ferrier A, Fossati F, Guerin S, Heuls S, Graux P. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1336-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822749&dopt=Abstract

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Mechano-electric feedback and atrial fibrillation. Author(s): Ravelli F. Source: Progress in Biophysics and Molecular Biology. 2003 May-July; 82(1-3): 137-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732274&dopt=Abstract

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Meta-analysis of antiarrhythmic therapy in the prevention of postoperative atrial fibrillation and the effect on hospital length of stay, costs, cerebrovascular accidents, and mortality in patients undergoing cardiac surgery. Author(s): Zimmer J, Pezzullo J, Choucair W, Southard J, Kokkinos P, Karasik P, Greenberg MD, Singh SN. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714166&dopt=Abstract

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Morphology of atrial myocardium in human pulmonary veins: a postmortem analysis in patients with and without atrial fibrillation. Author(s): Hassink RJ, Aretz HT, Ruskin J, Keane D. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 110814. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678939&dopt=Abstract

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Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. Author(s): Pappone C, Rosanio S, Augello G, Gallus G, Vicedomini G, Mazzone P, Gulletta S, Gugliotta F, Pappone A, Santinelli V, Tortoriello V, Sala S, Zangrillo A, Crescenzi G, Benussi S, Alfieri O. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 185-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875749&dopt=Abstract

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New atrial fibrillation and elective surgery. Author(s): Oxorn D. Source: Anesthesiology. 2003 September; 99(3): 756; Author Reply 757. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960567&dopt=Abstract

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New technique for simultaneous catheter mapping of pulmonary veins for catheter ablation in focal atrial fibrillation. Author(s): Kumagai K, Gondo N, Matsumoto N, Noguchi H, Tojo H, Yasuda T, Nakashima H, Saku K. Source: Cardiology. 2000; 94(4): 233-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11326144&dopt=Abstract

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Nicotine gum-induced atrial fibrillation. Author(s): Choragudi NL, Aronow WS, DeLuca AJ. Source: Heart Disease. 2003 March-April; 5(2): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713677&dopt=Abstract

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NO hope for patients with atrial fibrillation. Author(s): Rubart M, Zipes DP. Source: Circulation. 2002 November 26; 106(22): 2764-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450999&dopt=Abstract

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Nonfluoroscopic magnetic electroanatomic mapping to facilitate focal pulmonary veins ablation for paroxysmal atrial fibrillation. Author(s): Tse HF, Lee KL, Fan K, Lau CP. Source: Pacing and Clinical Electrophysiology : Pace. 2002 January; 25(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11877938&dopt=Abstract

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Non-invasive assessment of atrial fibrillation (AF) cycle length in man: potential application for studying AF. Author(s): Meurling CJ, Sornmo L, Stridh M, Olsson SB. Source: Ann Ist Super Sanita. 2001; 37(3): 341-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889950&dopt=Abstract

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Non-linear time series analysis: methods and applications to atrial fibrillation. Author(s): Hoekstra BP, Diks CG, Allessie MA, Degoede J. Source: Ann Ist Super Sanita. 2001; 37(3): 325-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889948&dopt=Abstract

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Nonpharmacological approaches to atrial fibrillation. Author(s): Scheinman MM, Morady F. Source: Circulation. 2001 April 24; 103(16): 2120-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11319205&dopt=Abstract

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Nonrheumatic atrial fibrillation and left ventricular hypertrophy in the prognosis of reversible ischaemic neurological deficit. Author(s): Atanassova PA, Vukov MI, Chalakova NT, Tokmakova MP, Dobreva BV. Source: Folia Med (Plovdiv). 2002; 44(4): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751684&dopt=Abstract

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Nonvalvular atrial fibrillation: an important cause of stroke. Author(s): Bornstein NM, Pavlovic AM. Source: Adv Neurol. 2003; 92: 203-12. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760184&dopt=Abstract

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Obstructive sleep apnea and the recurrence of atrial fibrillation. Author(s): Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, Shamsuzzaman AS, Somers VK. Source: Circulation. 2003 May 27; 107(20): 2589-94. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743002&dopt=Abstract

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Off-pump coronary artery bypass graft surgery: the incidence of postoperative atrial fibrillation. Author(s): Archbold RA, Curzen NP. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1134-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975397&dopt=Abstract

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Off-pump coronary artery bypass grafting does not decrease the incidence of atrial fibrillation. Author(s): Salamon T, Michler RE, Knott KM, Brown DA. Source: The Annals of Thoracic Surgery. 2003 February; 75(2): 505-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607662&dopt=Abstract

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Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. Author(s): Naccarelli GV, Wolbrette DL, Khan M, Bhatta L, Hynes J, Samii S, Luck J. Source: The American Journal of Cardiology. 2003 March 20; 91(6A): 15D-26D. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670638&dopt=Abstract

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On the outcome in stroke patients one year later: the role of atrial fibrillation. Author(s): Cisternino MD, Giaquinto S, Maiolo I, Palma E, Valeriani M, Vittoria E. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 January; 10(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534996&dopt=Abstract

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Optimal investigation of the elderly and very elderly patient with atrial fibrillation-what must be done? Author(s): Vlietstra RE. Source: The American Journal of Geriatric Cardiology. 2002 November-December; 11(6): 376-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417844&dopt=Abstract

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Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. Author(s): van Walraven C, Hart RG, Singer DE, Laupacis A, Connolly S, Petersen P, Koudstaal PJ, Chang Y, Hellemons B. Source: Jama : the Journal of the American Medical Association. 2002 November 20; 288(19): 2441-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435257&dopt=Abstract

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Oral loading single dose flecainide for pharmacological cardioversion of recent-onset atrial fibrillation. Author(s): Khan IA. Source: International Journal of Cardiology. 2003 February; 87(2-3): 121-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559528&dopt=Abstract

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Ought dialysis patients with atrial fibrillation be treated with oral anticoagulants? Author(s): Vazquez E, Sanchez-Perales C, Garcia-Cortes MJ, Borrego F, Lozano C, Guzman M, Gil JM, Liebana A, Perez P, Borrego MJ, Perez V. Source: International Journal of Cardiology. 2003 February; 87(2-3): 135-9; Discussion 139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559531&dopt=Abstract

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Overexpression of heat shock protein 60/10 in myocardium of patients with chronic atrial fibrillation. Author(s): Schafler AE, Kirmanoglou K, Pecher P, Hannekum A, Schumacher B. Source: The Annals of Thoracic Surgery. 2002 September; 74(3): 767-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12238837&dopt=Abstract

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Pacemaker prevention therapies for the control of drug-refractory paroxysmal atrial fibrillation. Author(s): Kale M, Bennett DH. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 2003 April; 5(2): 123-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633635&dopt=Abstract

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Patient education series. Patient-education guide: atrial fibrillation. Author(s): Adkins L. Source: Nursing. 2003 July; 33(7): 46-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851500&dopt=Abstract

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Persistent atrial fibrillation: rate control or rhythm control. Rate control is not inferior to rhythm control. Author(s): Boos CJ, More RS, Carlsson J. Source: Bmj (Clinical Research Ed.). 2003 June 28; 326(7404): 1411-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829529&dopt=Abstract

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Platelet activation, haemorheology and thrombogenesis in acute atrial fibrillation: a comparison with permanent atrial fibrillation. Author(s): Kamath S, Blann AD, Chin BS, Lip GY. Source: Heart (British Cardiac Society). 2003 September; 89(9): 1093-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923042&dopt=Abstract

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Predictors of warfarin use among Ohio medicaid patients with new-onset nonvalvular atrial fibrillation. Author(s): Johnston JA, Cluxton RJ Jr, Heaton PC, Guo JJ, Moomaw CJ, Eckman MH. Source: Archives of Internal Medicine. 2003 July 28; 163(14): 1705-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885686&dopt=Abstract

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Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Author(s): Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY. Source: Circulation. 2003 July 1; 107(25): 3141-5. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796127&dopt=Abstract

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Propafenone versus ibutilide for post operative atrial fibrillation following cardiac surgery: neither strategy improves outcomes compared to rate control alone (the PIPAF study). Author(s): Soucier R, Silverman D, Abordo M, Jaagosild P, Abiose A, Madhusoodanan KP, Therrien M, Lippman N, Dalamagas H, Berns E. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 March; 9(3): Pi19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640352&dopt=Abstract

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Prospective assessment of late conduction recurrence across radiofrequency lesions producing electrical disconnection at the pulmonary vein ostium in patients with atrial fibrillation. Author(s): Cappato R, Negroni S, Pecora D, Bentivegna S, Lupo PP, Carolei A, Esposito C, Furlanello F, De Ambroggi L. Source: Circulation. 2003 September 30; 108(13): 1599-604. Epub 2003 Sep 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963643&dopt=Abstract

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Pulmonary vein internal electrical activity does not contribute to the maintenance of atrial fibrillation. Author(s): Ndrepepa G, Schneider MA, Karch MR, Weber S, Schreieck J, Schomig A, Schmitt C. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1356-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822752&dopt=Abstract

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Pulmonary vein isolation using transvenous catheter cryoablation for treatment of atrial fibrillation without risk of pulmonary vein stenosis. Author(s): Tse HF, Reek S, Timmermans C, Lee KL, Geller JC, Rodriguez LM, Ghaye B, Ayers GM, Crijns HJ, Klein HU, Lau CP. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 752-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932615&dopt=Abstract

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QRS aberration during atrial fibrillation at rest and during exercise. Effect of a selective potassium channel blocking agent. Author(s): Houltz B, Darpo B, Crijns HJ, Swedberg K, Blomstrom P, Jensen SM, Svernhage E, Edvardsson N. Source: Journal of Electrocardiology. 2002 July; 35(3): 201-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122610&dopt=Abstract

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QRST subtraction combined with a pacemap catalogue for the prediction of ectopy source by surface electrocardiogram in patients with paroxysmal atrial fibrillation. Author(s): Choi KJ, Shah DC, Jais P, Hocini M, Macle L, Scavee C, Weerasooriya R, Raybaud F, Clementy J, Haissaguerre M. Source: Journal of the American College of Cardiology. 2002 December 4; 40(11): 201321. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475463&dopt=Abstract

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Quadruple pads approach for external cardioversion of atrial fibrillation. Author(s): Marrouche NF, Bardy GH, Frielitz HJ, Gunther J, Brachmann J. Source: Pacing and Clinical Electrophysiology : Pace. 2001 September; 24(9 Pt 1): 1321-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584453&dopt=Abstract

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Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. Author(s): Dorian P, Paquette M, Newman D, Green M, Connolly SJ, Talajic M, Roy D. Source: American Heart Journal. 2002 June; 143(6): 984-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075253&dopt=Abstract

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Quality of life in atrial fibrillation: relevance of the autonomic nervous system. Author(s): Lewalter T, Luderitz B. Source: European Heart Journal. 2001 February; 22(3): 196-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161929&dopt=Abstract

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Quality of life in nonpharmacologic treatment of atrial fibrillation. Author(s): Engelmann MD, Pehrson S. Source: European Heart Journal. 2003 August; 24(15): 1387-400. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909067&dopt=Abstract

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Quality of life in patients with paroxysmal atrial fibrillation and its predictors: importance of the autonomic nervous system. Author(s): van den Berg MP, Hassink RJ, Tuinenburg AE, van Sonderen EF, Lefrandt JD, de Kam PJ, van Gelder IC, Smit AJ, Sanderman R, Crijns HJ. Source: European Heart Journal. 2001 February; 22(3): 247-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161936&dopt=Abstract

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Quality of life in patients with silent atrial fibrillation. Author(s): Savelieva I, Paquette M, Dorian P, Luderitz B, Camm AJ. Source: Heart (British Cardiac Society). 2001 February; 85(2): 216-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156677&dopt=Abstract

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Quality-of-life in patients with paroxysmal atrial fibrillation after catheter ablation: results of long-term follow-up. Author(s): Erdogan A, Carlsson J, Neumann T, Berkowitsch A, Neuzner J, Hamm CW, Pitschner HF. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 678-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698667&dopt=Abstract

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Quantification of left atrial appendage spontaneous echo contrast in patients with chronic nonalvular atrial fibrillation. Author(s): Ito T, Suwa M, Nakamura T, Miyazaki S, Kobashi A, Kitaura Y. Source: J Cardiol. 2001 June; 37(6): 325-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11433808&dopt=Abstract

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Radiofrequency ablation for atrial fibrillation. Author(s): Sriratanasathavorn C. Source: J Med Assoc Thai. 2003 May; 86 Suppl 1: S83-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866773&dopt=Abstract

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Rate control in atrial fibrillation. Author(s): Boos C, More R. Source: Clinical Medicine (London, England). 2003 May-June; 3(3): 291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848272&dopt=Abstract

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Rate control in atrial fibrillation: choice of treatment and assessment of efficacy. Author(s): Boriani G, Biffi M, Diemberger I, Martignani C, Branzi A. Source: Drugs. 2003; 63(14): 1489-509. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834366&dopt=Abstract

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Rate control versus rhythm control for the management of atrial fibrillation: the verdict of the AFFIRM trial. Author(s): Salam AM. Source: Expert Opinion on Investigational Drugs. 2003 July; 12(7): 1231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831357&dopt=Abstract

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Reduced lung function and risk of atrial fibrillation in the Copenhagen City Heart Study. Author(s): Buch P, Friberg J, Scharling H, Lange P, Prescott E. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 June; 21(6): 1012-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797497&dopt=Abstract

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Restoring sinus rhythm in atrial fibrillation: a Pyrrhic victory? Author(s): Dorian P, Mangat I. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 30-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849655&dopt=Abstract

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Reversal of atrial mechanical dysfunction after cardioversion of atrial fibrillation: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy. Author(s): Sanders P, Morton JB, Kistler PM, Vohra JK, Kalman JM, Sparks PB. Source: Circulation. 2003 October 21; 108(16): 1976-84. Epub 2003 Oct 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557372&dopt=Abstract

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Reverse remodeling of sinus node function after catheter ablation of atrial fibrillation in patients with prolonged sinus pauses. Author(s): Hocini M, Sanders P, Deisenhofer I, Jais P, Hsu LF, Scavee C, Weerasoriya R, Raybaud F, Macle L, Shah DC, Garrigue S, Le Metayer P, Clementy J, Haissaguerre M. Source: Circulation. 2003 September 9; 108(10): 1172-5. Epub 2003 Sep 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952840&dopt=Abstract

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Risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter. Author(s): Reithmann C, Dorwarth U, Dugas M, Hahnefeld A, Ramamurthy S, Remp T, Steinbeck G, Hoffmann E. Source: European Heart Journal. 2003 July; 24(13): 1264-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831821&dopt=Abstract

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Safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications in patients with atrial fibrillation or atrial flutter. Author(s): Hauser TH, Pinto DS, Josephson ME, Zimetbaum P. Source: The American Journal of Cardiology. 2003 June 15; 91(12): 1437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804730&dopt=Abstract

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Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction. Author(s): Ozcan C, Jahangir A, Friedman PA, Munger TM, Packer DL, Hodge DO, Hayes DL, Gersh BJ, Hammill SC, Shen WK. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842241&dopt=Abstract

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Simultaneous multisite endocardial mapping of sustained and non-sustained atrial fibrillation in humans. Author(s): Karch MR, Ndrepepa G, Zrenner B, Saur C, Schneider MA, Schomig A, Schmitt CS. Source: J Invasive Cardiol. 2003 May; 15(5): 257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730633&dopt=Abstract

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Single chamber atrial fibrillation involving only the left atrium: implications for maintenance and radiofrequency ablation therapy. Author(s): Karch MR, Ndrepepa G, Schneider MA, Weber S, Schreieck J, Schmitt C. Source: Pacing and Clinical Electrophysiology : Pace. 2003 April; 26(4 Pt 1): 883-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715850&dopt=Abstract

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Single-beat determination of Doppler-derived aortic flow measurement in patients with atrial fibrillation. Author(s): Sumida T, Tanabe K, Yagi T, Kawai J, Konda T, Fujii Y, Okada M, Yamaguchi K, Tani T, Morioka S. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 July; 16(7): 712-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835656&dopt=Abstract

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Stroke and atrial fibrillation following cardiac surgery. Author(s): Murdock DK, Rengel LR, Schlund A, Olson KJ, Kaliebe JW, Johnkoski JA, Riveron FA. Source: Wmj. 2003; 102(4): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967018&dopt=Abstract

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Stroke prevention in atrial fibrillation. Author(s): Waldo AL. Source: Jama : the Journal of the American Medical Association. 2003 August 27; 290(8): 1093-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941684&dopt=Abstract

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Sudden death due to atrial fibrillation in hypertrophic cardiomyopathy: a predictable event in a young patient. Author(s): Favale S, Pappone C, Nacci F, Fino F, Resta F, Dicandia CD. Source: Pacing and Clinical Electrophysiology : Pace. 2003 February; 26(2 Pt 1): 637-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722693&dopt=Abstract

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Sustained atrial tachycardia in heart failure: is it the precursor to atrial fibrillation? Author(s): Goldberger JJ. Source: Journal of Cardiovascular Electrophysiology. 2003 May; 14(5): 508-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776868&dopt=Abstract

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Symptoms at the time of arrhythmia recurrence in patients receiving azimilide for control of atrial fibrillation or flutter: results from randomized trials. Author(s): Connolly SJ, Schnell DJ, Page RL, Wilkinson WE, Marcello SR, Pritchett EL; Azimilide Supraventricular Arrhythmia Program Investigators. Source: American Heart Journal. 2003 September; 146(3): 489-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947368&dopt=Abstract

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Tedisamil in coronary disease: additional benefits in the therapy of atrial fibrillation? Author(s): Opie LH. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 June; 8 Suppl 1: S33-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746750&dopt=Abstract

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Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Author(s): Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D'Agostino RB, Murabito JM, Kannel WB, Benjamin EJ. Source: Circulation. 2003 June 17; 107(23): 2920-5. Epub 2003 May 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771006&dopt=Abstract

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Termination of persistent atrial fibrillation resistant to cardioversion by a single radiofrequency application. Author(s): Herweg B, Kowalski M, Steinberg JS. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1420-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822761&dopt=Abstract

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The -174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication? Author(s): Gaudino M, Andreotti F, Zamparelli R, Di Castelnuovo A, Nasso G, Burzotta F, Iacoviello L, Donati MB, Schiavello R, Maseri A, Possati G. Source: Circulation. 2003 September 9; 108 Suppl 1: Ii195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970232&dopt=Abstract

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The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial (AIRCRAFT). Author(s): Weerasooriya R, Davis M, Powell A, Szili-Torok T, Shah C, Whalley D, Kanagaratnam L, Heddle W, Leitch J, Perks A, Ferguson L, Bulsara M. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1697-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767649&dopt=Abstract

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The prevalence of atrial fibrillation in incident stroke cases and matched population controls in Rochester, Minnesota: changes over three decades. Author(s): Tsang TS, Petty GW, Barnes ME, O'Fallon WM, Bailey KR, Wiebers DO, Sicks JD, Christianson TJ, Seward JB, Gersh BJ. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849666&dopt=Abstract

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The safety of low-molecular weight heparins for the prevention of thromboembolic events after cardioversion of atrial fibrillation. Author(s): Yigit Z, Kucukoglu MS, Okcun B, Sansoy V, Guzelsoy D. Source: Japanese Heart Journal. 2003 May; 44(3): 369-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825804&dopt=Abstract

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Thoracoscopic extracardiac obliteration of the left atrial appendage for stroke risk reduction in atrial fibrillation. Author(s): Blackshear JL, Johnson WD, Odell JA, Baker VS, Howard M, Pearce L, Stone C, Packer DL, Schaff HV. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1249-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522490&dopt=Abstract

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Total pulmonary vein occlusion as a consequence of catheter ablation for atrial fibrillation mimicking primary lung disease. Author(s): Ernst S, Ouyang F, Goya M, Lober F, Schneider C, Hoffmann-Riem M, Schwarz S, Hornig K, Muller KM, Antz M, Kaukel E, Kugler C, Kuck KH. Source: Journal of Cardiovascular Electrophysiology. 2003 April; 14(4): 366-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741706&dopt=Abstract

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Transesophageal echocardiography before cardioversion of recurrent atrial fibrillation: does absence of previous atrial thrombi preclude the need of a repeat test? Author(s): Shen X, Li H, Rovang K, Hee T, Holmberg MJ, Mooss AN, Mohiuddin SM. Source: American Heart Journal. 2003 October; 146(4): 741-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564332&dopt=Abstract

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Underutilization of anticoagulation therapy in chronic atrial fibrillation. Author(s): Guo GB, Chang HW, Chen MC, Yang CH. Source: Japanese Heart Journal. 2001 January; 42(1): 55-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11324807&dopt=Abstract

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Use of intracardiac echocardiography for prediction of chronic pulmonary vein stenosis after ablation of atrial fibrillation. Author(s): Saad EB, Cole CR, Marrouche NF, Dresing TJ, Perez-Lugones A, Saliba WI, Schweikert RA, Klein A, Rodriguez L, Grimm R, Tchou P, Natale A. Source: Journal of Cardiovascular Electrophysiology. 2002 October; 13(10): 986-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435183&dopt=Abstract

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Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Author(s): Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A, Cano L, Cano JM, Cabeza P, Moro C. Source: Circulation. 2002 July 16; 106(3): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119249&dopt=Abstract

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Use of remifentanil in fast atrial fibrillation. Author(s): Williams H, Spoelstra C. Source: British Journal of Anaesthesia. 2002 April; 88(4): 614. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066756&dopt=Abstract

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Use of transesophageal contrast echocardiography for excluding left atrial appendage thrombi in patients with atrial fibrillation before cardioversion. Author(s): von der Recke G, Schmidt H, Illien S, Luderitz B, Omran H. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2002 October; 15(10 Pt 2): 1256-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411914&dopt=Abstract

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Use patterns of low-molecular weight heparin and the impact on length of stay in patients hospitalized for atrial fibrillation. Author(s): Kim MH, Decena BF, Bruckman D, Eagle KA. Source: American Heart Journal. 2003 April; 145(4): 665-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679763&dopt=Abstract

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Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm. Author(s): Fujiki A, Tsuneda T, Sugao M, Mizumaki K, Inoue H. Source: The American Journal of Cardiology. 2003 August 15; 92(4): 472-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914884&dopt=Abstract

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Usefulness of atrial fibrillation as a marker of outcome after percutaneous coronary intervention. Author(s): El-Omar MM, Dangas G, Mehran R, Lansky AJ, Kipshidze NN, Polena S, Fahy M, Moussa I, Glasser L, Moses JW, Stone GW, Leon MB. Source: The American Journal of Cardiology. 2003 January 15; 91(2): 232-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521640&dopt=Abstract

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Usefulness of atrial pacing for prevention and termination of atrial tachyarrhythmias in a patient with persistent atrial fibrillation. Author(s): Israel CW, Gronefeld G, Li YG, Hohnloser SH. Source: Pacing and Clinical Electrophysiology : Pace. 2002 October; 25(10): 1527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418754&dopt=Abstract

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Usefulness of electron beam tomography in the prone position for detecting atrial thrombi in chronic atrial fibrillation. Author(s): Tani T, Yamakami S, Matsushita T, Okamoto M, Toyama J, Suzuki S, Fukutomi T, Itoh M. Source: Journal of Computer Assisted Tomography. 2003 January-February; 27(1): 78-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544247&dopt=Abstract

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Vagal stimulation and atrial fibrillation: experimental models and clinical uncertainties. Author(s): Wilber DJ, Morton JB. Source: Journal of Cardiovascular Electrophysiology. 2002 December; 13(12): 1280-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521346&dopt=Abstract

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Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. Author(s): Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Source: Jama : the Journal of the American Medical Association. 2001 June 13; 285(22): 2864-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401607&dopt=Abstract

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Value of isolating the pulmonary veins in the treatment of atrial fibrillation. Sinus rhythm recovery after pulmonary vein isolation and persistent fibrillation inside the disconnected pulmonary veins. Author(s): Adragao P, Aguiar C, Morgado F, Cavaco D, Bonhorst D, e Melo JQ, SeabraGomes R. Source: Rev Port Cardiol. 2002 February; 21(2): 221-7. English, Portuguese. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11963290&dopt=Abstract

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Value of precardioversion transesophageal echocardiography in managing cardioversion in atrial fibrillation. Author(s): Manning WJ, Silverman DI, Seto TB, Weigner MJ. Source: Journal of the American College of Cardiology. 2002 November 20; 40(10): 1889; Author Reply 1889-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446076&dopt=Abstract

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Variability in the manifestation of pre-excited atrial fibrillation: its quantification, theoretical origin, and diagnostic potential. Author(s): Lau EW, Ng GA, Griffith MJ. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2001 April; 6(2): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11333168&dopt=Abstract

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Variation in the utilization of antiarrhythmic drugs in patients with new-onset atrial fibrillation. Author(s): Zimetbaum P, Ho KK, Olshansky B, Hadjis T, Lemery R, Friedman PA, Cannom DS, Chen XH, Josephson ME; FRACTAL Investigators. Source: The American Journal of Cardiology. 2003 January 1; 91(1): 81-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505578&dopt=Abstract

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Ventricular fibrillation during electrical cardioversion of pre-excited atrial fibrillation. Author(s): Adlam D, Azeem T. Source: Postgraduate Medical Journal. 2003 May; 79(931): 297-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782780&dopt=Abstract

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Ventricular rate control in atrial fibrillation: what is the optimal rate? The concept of controlling the heart rate burden. Author(s): Singh BN. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 March; 8(1): 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652323&dopt=Abstract

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VErapamil plus antiarrhythmic drugs reduce atrial fibrillation recurrences after an electrical cardioversion (VEPARAF Study). Author(s): De Simone A, De Pasquale M, De Matteis C, Canciello M, Manzo M, Sabino L, Alfano F, Di Mauro M, Campana A, De Fabrizio G, Vitale DF, Turco P, Stabile G. Source: European Heart Journal. 2003 August; 24(15): 1425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909071&dopt=Abstract

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VERDICT: the Verapamil versus Digoxin Cardioversion Trial: A randomized study on the role of calcium lowering for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation. Author(s): Van Noord T, Van Gelder IC, Tieleman RG, Bosker HA, Tuinenburg AE, Volkers C, Veeger NJ, Crijns HJ. Source: Journal of Cardiovascular Electrophysiology. 2001 July; 12(7): 766-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469424&dopt=Abstract

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Warfarin for non-valvar atrial fibrillation: still underused in the 21st century? Author(s): Bo S, Ciccone G, Scaglione L, Taliano C, Piobbici M, Merletti F, Pagano G. Source: Heart (British Cardiac Society). 2003 May; 89(5): 553-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695466&dopt=Abstract

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Warfarin for nonvalvular atrial fibrillation in primary care--another example of the age paradox? Author(s): Burton CD, Hamilton KE, Isles CG, Norrie J. Source: Journal of Cardiovascular Risk. 2001 October; 8(5): 307-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702037&dopt=Abstract

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Warfarin for stroke prevention in octogenarians with atrial fibrillation. Author(s): Howard PA, Ellerbeck EF, Engelman KK, Dunn MI. Source: The American Journal of Geriatric Cardiology. 2001 May-June; 10(3): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11360838&dopt=Abstract

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Warfarin therapy for an octogenarian who has atrial fibrillation. Author(s): Gage BF, Fihn SD, White RH. Source: Annals of Internal Medicine. 2001 March 20; 134(6): 465-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255522&dopt=Abstract

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Warfarin therapy for atrial fibrillation in the elderly. Author(s): Lackie CL, Garbarino KA, Pruetz JA. Source: The Annals of Pharmacotherapy. 2002 February; 36(2): 200-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847934&dopt=Abstract

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Warfarin use in atrial fibrillation: A random sample survey of family physician beliefs and preferences. Author(s): Pradhan AA, Levine MA. Source: Can J Clin Pharmacol. 2002 Winter; 9(4): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584578&dopt=Abstract

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What characterizes episodes of atrial fibrillation requiring cardioversion? Experience from patients with an implantable atrial cardioverter. Author(s): Frykman V, Ayers GM, Darpo B, Rosenqvist M. Source: American Heart Journal. 2003 April; 145(4): 670-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679764&dopt=Abstract

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When to convert atrial fibrillation? Author(s): Sorrentino MJ. Source: Postgraduate Medicine. 2003 June; 113(6): 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838801&dopt=Abstract

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Which acute stroke patients with atrial fibrillation are prescribed warfarin therapy? Results from one-year's experience in Dundee. Author(s): Craig J, MacWalter RS, Goudie BM. Source: Scott Med J. 2000 August; 45(4): 110-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060912&dopt=Abstract

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With pulmonary vein isolation for paroxysmal atrial fibrillation ablation, one size does not fit all. Author(s): Haines DE. Source: Journal of Cardiovascular Electrophysiology. 2002 October; 13(10): 962-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435179&dopt=Abstract

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Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Author(s): Halperin JL; Executive Steering Committee, SPORTIF III and V Study Investigators. Source: American Heart Journal. 2003 September; 146(3): 431-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947359&dopt=Abstract

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Ximelagatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. SPORTIF II: a dose-guiding, tolerability, and safety study. Author(s): Petersen P, Grind M, Adler J; SPORTIF II Investigators. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742279&dopt=Abstract

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CHAPTER 2. NUTRITION AND ATRIAL FIBRILLATION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and atrial fibrillation.

Finding Nutrition Studies on Atrial Fibrillation The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “atrial fibrillation” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on atrial fibrillation: •

Anticoagulant therapy for atrial fibrillation. Recommendations from major studies. Author(s): Michigan Heart and Vascular Institute, St Joseph Mercy Hospital, Ann Arbor. Source: Kahn, J K Postgrad-Med. 1992 September 1; 92(3): 119-24, 129-30 0032-5481

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Anticoagulant therapy in recurrent cerebral embolism: a retrospective study in nonvalvular atrial fibrillation. Author(s): Department of Neurology, Tokyo Metropolitan Geriatric Hospital, Japan. Source: Yamanouchi, H Nagura, H Ohkawa, Y Sakurai, Y Kuzuhara, S Kuramoto, K Shimada, H Toyokura, Y J-Neurol. 1988 September; 235(7): 407-10 0340-5354

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Anticoagulation in patients with valvular heart disease, atrial fibrillation, or both. Author(s): Department of Medicine, Albert Einstein College of Medicine, Bronx, New York. Source: Kadish, S L Lazar, E J Frishman, W H Cardiol-Clin. 1987 November; 5(4): 591628 0733-8651

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Anticoagulation therapy for atrial fibrillation and coronary disease. Author(s): Yale University School of Medicine, New Haven, Connecticut, USA. Source: Ezekowitz, M D J-Thromb-Thrombolysis. 2000 June; 9 Suppl 1S47-51 0929-5305

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Antithrombotic therapy for stroke prevention among Medicare beneficiaries hospitalized in Alaska with atrial fibrillation. Author(s): PRO-West/Alaska, Anchorage 99508, USA. Source: Gordian, M E Mustin, H D Alaska-Med. 1998 Oct-December; 40(4): 79-84 00024538

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Asymptomatic embolisation in non-valvular atrial fibrillation and its relationship to anticoagulation therapy. Author(s): Department of Surgery, Royal Free Hampstead NHS Trust, London, UK. Source: Tinkler, Kerry Cullinane, Marisa Kaposzta, Zoltan Markus, Hugh S Eur-JUltrasound. 2002 June; 15(1-2): 21-7 0929-8266

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Atrial fibrillation and anabolic steroids. Author(s): Department of Emergency Medicine, Jacobi Medical Center, Bronx, New York, USA. Source: Sullivan, M L Martinez, C M Gallagher, E J J-Emerg-Med. 1999 Sep-October; 17(5): 851-7 0736-4679

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Atrial fibrillation and anticoagulation in patients with permanent pacemakers: implications for stroke prevention. Author(s): Department of Cardiology, Royal Melbourne Hospital, Parkville, Victoria, Australia. Source: Sparks, P B Mond, H G Kalman, J M Jayaprakash, S Lewis, M A Grigg, L E Pacing-Clin-Electrophysiol. 1998 June; 21(6): 1258-67 0147-8389

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Atrial fibrillation and anticoagulation. Author(s): Stanford University School of Medicine, Palo Alto, California, USA. Source: Marcus, R R Atwood, J E Adv-Intern-Med. 1999; 44239-65 0065-2822

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Atrial fibrillation threshold predicted long-term efficacy of pharmacological treatment of patients without structural heart disease. Author(s): Kyoto Prefectural University of Medicine, Second Department of Medicine, Kawaramachi Hirokoji, Japan. [email protected] Source: Shirayama, T Shiraishi, H Yoshida, S Matoba, Y Imai, H Nakagawa, M Europace. 2002 October; 4(4): 383-9 1099-5129

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Atrial fibrillation. Source: Anonymous Harv-Mens-Health-Watch. 1998 April; 2(9): 1-4 1089-1102

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Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies. Author(s): Department of Medicine (Neurology), University of Texas Health Science Center, San Antonio, TX 78284, USA. Source: Hart, R G Pearce, L A Miller, V T Anderson, D C Rothrock, J F Albers, G W Nasco, E Cerebrovasc-Dis. 2000 Jan-February; 10(1): 39-43 1015-9770

•

Cost-Effectiveness of antiarrhythmic drugs for prevention of thromboembolism in patients with paroxysmal atrial fibrillation. Source: Anonymous Jpn-Circ-J. 2001 September; 65(9): 765-8 0047-1828

•

Development and description of a decision analysis based decision support tool for stroke prevention in atrial fibrillation. Author(s): Department of Epidemiology and Public Health, School of Health Sciences, Newcastle Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. [email protected] Source: Thomson, Richard Robinson, Angela Greenaway, Jane Lowe, Philip QualHealth-Care. 2002 March; 11(1): 25-31 0963-8172

•

Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. Author(s): Department of Medicine, Dalhousie University, Halifax, Nova Scotia, B3K 6A3, Canada. [email protected] Source: Devereaux, P J Anderson, D R Gardner, M J Putnam, W Flowerdew, G J Brownell, B F Nagpal, S Cox, J L BMJ. 2001 November 24; 323(7323): 1218-22 0959-8138

•

Doctors' beliefs on the use of antithrombotic therapy in atrial fibrillation: identifying barriers to stroke prevention. Author(s): are important strategies for targeting barriers to the use of anticoagulation for stroke prevention. Source: Peterson, G M Boom, K Jackson, S L Vial, J H Intern-Med-J. 2002 Jan-February; 32(1-2): 15-23 1444-0903

•

Does lone atrial fibrillation constitute a risk of embolization, and how should we manage it? Author(s): American University Hospital, Beirut, Lebanon. Source: Sawaya, J I J-Med-Liban. 1992; 40(2): 117 0023-9852

•

Effect of low-intensity warfarin therapy on left atrial thrombus resolution in patients with nonvalvular atrial fibrillation: a transesophageal echocardiographic study. Author(s): Second Department of Internal Medicine, Yamaguchi University School of Medicine, Japan. Source: Kimura, M Wasaki, Y Ogawa, H Nakatsuka, M Wakeyama, T Iwami, T Ono, K Nakao, F Matsuzaki, M Jpn-Circ-J. 2001 April; 65(4): 271-4 0047-1828

•

Effects of MgSO4 and glucose, insulin and potassium (GIK) on atrial conduction during the first 12 hours after DC-conversion of chronic atrial fibrillation. Author(s): Department of Cardiology, Lund University, Sweden. Source: Ingemansson, M P Carlson, J PlatoNovember, P Olsson, S B Scand-Cardiovasc-J. 2001 October; 35(5): 340-6 1401-7431


•

Ethnic differences in patient perceptions of atrial fibrillation and anticoagulation therapy: the West Birmingham Atrial Fibrillation Project. Author(s): University Department of Medicine, City Hospital, Birmingham, England. [email protected] Source: Lip, Gregory Y H Kamath, Sridhar Jafri, Marian Mohammed, Afzal Bareford, David Stroke. 2002 January; 33(1): 238-42 1524-4628

•

Idiopathic atrial fibrillation in a champion Standardbred racehorse. Author(s): School of Veterinary Science, University of Melbourne, Parkville, Victoria. Source: Stewart, G A Fulton, L J McKellar, C D Aust-Vet-J. 1990 May; 67(5): 187-91 00050423

•

Impaired exercise-induced vasodilatation in chronic atrial fibrillation--role of endothelium-derived nitric oxide. Author(s): Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan. Source: Takahashi, N Ishibashi, Y Shimada, T Sakane, T Ohata, S Sugamori, T Ohta, Y Inoue, S Nakamura, K Shimizu, H Katoh, H Murakami, Y Circ-J. 2002 June; 66(6): 583-8 1346-9843

•

Improving management of atrial fibrillation and anticoagulation in a community hospital. Author(s): Carney Hospital Anticoagulation Clinic, Boston, USA. Source: Gaughan, G L Dolan, C Wilk Rivard, E Geary, G Libbey, R Gilman, M A Lanata, H Jt-Comm-J-Qual-Improvolume 2000 January; 26(1): 18-28 1070-3241

•

Instability of anticoagulation intensity contributes to occurrence of ischemic stroke in patients with non-rheumatic atrial fibrillation. Author(s): The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan. [email protected] Source: Nozawa, T Asanoi, H Inoue, H Jpn-Circ-J. 2001 May; 65(5): 404-8 0047-1828

•

Intracardiac overdrive pacing as a treatment of atrial flutter in a horse. Author(s): Department of Internal Medicine and Clinical Biology of Large Animal, Faculty of Veterinary Medicine, University of Ghent, Merelbeke, Belgium. Source: Van Loon, G Jordaens, L Muylle, E Nollet, H Sustronck, B Vet-Rec. 1998 March 21; 142(12): 301-3 0042-4900

•

Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor? Author(s): Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK. Source: Chung, N A Belgore, F Li Saw Hee, F L Conway, D S Blann, A D Lip, G Y Stroke. 2002 September; 33(9): 2187-91 1524-4628

•

Left atrial and appendage mechanical function after pharmacological or electrical cardioversion in patients with chronic atrial fibrillation: a multicenter, randomized study. Author(s): Emergency Medicine Maggiore Hospital, Italy. Source: Mazzone, C Pandullo, C Scardi, S Salvi, R Miccio, M Cattarini, G Morgera, T ItalHeart-J. 2000 February; 1(2): 128-36 1129-471X

•

Long-term pharmacologic management of atrial fibrillation in the elderly. Author(s): Department of Medicine, Division of Cardiology, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH 44106, USA. [email protected]

Nutrition

103

Source: Waldo, A L Am-J-Geriatr-Cardiol. 2002 Jul-August; 11(4): 233-44; quiz 244-6 1076-7460 •

Long-term prevention of atrial fibrillation after coronary artery bypass surgery: comparison of quinidine, verapamil, and amiodarone in maintaining sinus rhythm. Author(s): Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey. Source: Yilmaz, A T Demirkilic, U Arslan, M Kurulay, E Ozal, E Tatar, H Ozturk, O JCard-Surg. 1996 Jan-February; 11(1): 61-4 0886-0440

•

Mechanisms of cardiac arrhythmias: focus on atrial fibrillation. Author(s): Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Source: Rosen, M R J-Gend-Specif-Med. 2001; 4(3): 37-47 1523-7036

•

Modification of intrinsic AV-nodal properties by magnesium in combination with glucose, insulin, and potassium (GIK) during chronic atrial fibrillation. Author(s): Department of Cardiology, Lund University, Sweden. Source: Ingemansson, M P Carlson, J Olsson, S B J-Electrocardiol. 1998 October; 31(4): 281-92 0022-0736

•

Natural history of atrial fibrillation. Author(s): Department of Cardiology, Heart Institute of Japan, Tokyo Women's Medical College. Source: Hirosawa, K Sekiguchi, M Kasanuki, H Kimata, S Kaneko, N Nakamura, K Aosaki, M Takahashi, S Kondo, M Heart-Vessels-Suppl. 1987; 214-23 0935-736X

•

New antiarrhythmic drugs for the treatment of atrial fibrillation. Author(s): Department of Heart Disease, S. Filippo Neri Hospital, Rome, Italy. [email protected] Source: Castro, A Bianconi, L Santini, M Pacing-Clin-Electrophysiol. 2002 February; 25(2): 249-59 0147-8389

•

Non-rheumatic atrial fibrillation and stroke. Author(s): Austin and Repatriation Medical Centre, Melbourne, Vic. Source: Tonkin, A Aust-N-Z-J-Med. 1999 June; 29(3): 467-72 0004-8291

•

Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation. Author(s): Cardiology Department, Piacenza General Hospital, Piacenza, Italy. Source: Capucci, A Villani, G Q Aschieri, D Rosi, A Piepoli, M F Eur-Heart-J. 2000 January; 21(1): 66-73 0195-668X

•

Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Author(s): Division of Neurology, Department of Medicine, University of Texas. Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7883, USA. [email protected]. Source: Benavente, O Hart, R Koudstaal, P Laupacis, A McBride, R Cochrane-DatabaseSyst-Revolume 2000; (2): CD001927 1469-493X

•

Oral magnesium reduces ventricular ectopy in digitalised patients with chronic atrial fibrillation. Author(s): Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland. Source: Lewis, R V Tregaskis, B McLay, J Service, E McDevitt, D G Eur-J-ClinPharmacol. 1990; 38(2): 107-10 0031-6970


•

Outcomes in the management of atrial fibrillation: clinical trial results can apply in practice. Author(s): Tasmanian School of Pharmacy, Faculty of Health Science, University of Tasmania, Hobart, Australia. Source: Jackson, S L Peterson, G M Vial, J H Daud, R Ang, S Y Intern-Med-J. 2001 August; 31(6): 329-36 1444-0903

•

Paroxysmal atrial fibrillation after high-dose melphalan in five patients autotransplanted with blood progenitor cells. Author(s): Clinica di Ematologia, Universita di Ancona, Italy. Source: Olivieri, A Corvatta, L Montanari, M Brunori, M Offidani, M Ferretti, G F Centanni, M Leoni, P Bone-Marrow-Transplant. 1998 May; 21(10): 1049-53 0268-3369

•

Paroxysmal atrial fibrillation in a young female patient following marijuana intoxication--a case report of possible association. Author(s): Department and Division of Internal Medicine and Cardiology, Medical University, ul. Banacha 1a, 02-097 Warsaw, Poland. Source: Kosior, D A Filipiak, K J Stolarz, P Opolski, G Med-Sci-Monit. 2000 Mar-April; 6(2): 386-9 1234-1010

•

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: I. Reduced flow velocity in the left atrial appendage (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study). Author(s): Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, NY 10029, USA. [email protected] Source: Goldman, M E Pearce, L A Hart, R G Zabalgoitia, M Asinger, R W Safford, R Halperin, J L J-Am-Soc-Echocardiogr. 1999 December; 12(12): 1080-7 0894-7317

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Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence. Author(s): Clinical Services Unit-Pharmaceutical Sciences, Vancouver Hospital and Health Sciences Center, University of British Columbia, Vancouver, BC, Canada. Source: Slavik, R S Tisdale, J E Borzak, S Prog-Cardiovasc-Dis. 2001 Sep-October; 44(2): 121-52 0033-0620

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Pharmacological therapy of atrial fibrillation. Author(s): J.W. Goethe-University, Frankfurt a. M., Germany. Source: Gronefeld, G Bender, B Li, Y G Hohnloser, S H Thorac-Cardiovasc-Surg. 1999 August; 47 Suppl 3334-8 0171-6425

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Plasmin-alpha2-antiplasmin complex in patients with atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators. Author(s): Department of Neurology, The University of Arizona, Tucson, USA. Source: Feinberg, W M Macy, E Cornell, E S Nightingale, S D Pearce, L A Tracy, R P Bovill, E G Thromb-Haemost. 1999 July; 82(1): 100-3 0340-6245

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Platelet P-selectin levels in relation to plasma soluble P-selectin and betathromboglobulin levels in atrial fibrillation. Author(s): Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK. Source: Kamath, Sridhar Blann, Andrew D Caine, Graham J Gurney, David Chin, Bernard S P Lip, Gregory Y H Stroke. 2002 May; 33(5): 1237-42 1524-4628

•

Platelets and atrial fibrillation. Author(s): Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.

Nutrition

105

Source: Kamath, S Blann, A D Lip, G Y Eur-Heart-J. 2001 December; 22(24): 2233-42 0195-668X •

Prescribing patterns for the use of antithrombotics in the management of atrial fibrillation in Zimbabwe. Author(s): [email protected] Source: Bhagat, K Tisocki, K Cent-Afr-J-Med. 1999 November; 45(11): 287-90 0008-9176

•

Prevalence of atrial fibrillation and antithrombotic prophylaxis in emergency department patients. Author(s): Department of Emergency Medicine, University of Michigan, Ann Arbor 48109, USA. [email protected] Source: Scott, P A Pancioli, A M Davis, L A Frederiksen, S M Eckman, J Stroke. 2002 November; 33(11): 2664-9 1524-4628

•

Safety and effectiveness of oral quinidine in cardioversion of persistent atrial fibrillation. Author(s): Division of Cardiology, Second Idrima Kinonikon Asfaliseon Hospital, N. Plastira 22 N Krini, Thessaloniki, Greece. Source: Kirpizidis, C Stavrati, A Geleris, P Boudoulas, H J-Cardiol. 2001 December; 38(6): 351-4 0914-5087

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Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation? Author(s): Department of Medicine, Guy's, King's & St Thomas' School of Medicine, King's College, London, UK. [email protected] Source: Evans, A Perez, I Yu, G Kalra, L Stroke. 2001 December 1; 32(12): 2828-32 15244628

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Stroke prevention as an indication for the Maze procedure in the treatment of atrial fibrillation. Author(s): Department of Thoracic and Cardiovascular Surgery, Georgetown University Medical Center, Washington, DC 20007, USA. Source: Ad, N Cox, J L Semin-Thorac-Cardiovasc-Surg. 2000 January; 12(1): 56-62 10430679

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Stroke prevention in elderly patients with atrial fibrillation. Author(s): Geriatric Unit, Changi General Hospital, Singapore. [email protected] Source: Lew, S J Lim, J K Singapore-Med-J. 2002 April; 43(4): 198-201 0037-5675

•

The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation. Author(s): Department of Cardiology, South Hospital, Sweden. Source: Frick, M Darpo, B Ostergren, J Rosenqvist, M Eur-Heart-J. 2000 July; 21(14): 1177-85 0195-668X

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The morbidity related to atrial fibrillation at a tertiary centre in one year: 9.0% of all strokes are potentially preventable. Author(s): Department of Neurology, The Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, 3050, Australia. [email protected] Source: Evans, A Davis, S Kilpatrick, C Gerraty, R Campbell, D Greenberg, P J-ClinNeurosci. 2002 May; 9(3): 268-72 0967-5868


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The tachycardia-induced dog model of atrial fibrillation. clinical relevance and comparison with other models. Author(s): Department of Pharmacology, Centre for Therapeutic Research, Merck Frosst Canada, 16711 Trans Canada Hwy., Kirkland, Quebec, Canada. [email protected] Source: Gaspo, R J-Pharmacol-Toxicol-Methods. 1999 September; 42(1): 11-20 1056-8719

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The ten most commonly asked questions about stroke prevention in atrial fibrillation. Author(s): The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York 10029-6574, USA. Source: Halperin, J L Cardiol-Revolume 2001 Jul-August; 9(4): 187-92 1061-5377

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Transoesophageal echocardiography-guided cardioversion of atrial fibrillation or flutter. Selection of a low-risk group for immediate cardioversion. Author(s): Department of Cardiology, University Hospital, Lund, Sweden. Source: Roijer, A Eskilsson, J Olsson, B Eur-Heart-J. 2000 May; 21(10): 837-47 0195-668X

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Treatment for atrial fibrillation complications. Author(s): University of Pittsburgh Medical Center, USA. [email protected] Source: Whittle, J Pa-Med. 2000 January; 103(1): 16 0031-4595

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Treatment of atrial fibrillation with warfarin in Rhode Island. Author(s): [email protected] Source: Gifford, D R Silverman, L R Med-Health-R-I. 2000 May; 83(5): 156-7 1086-5462

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Treatment of chronic nonvalvular atrial fibrillation in the elderly: a decision analysis. Author(s): Division of General Internal Medicine, Geriatric Medicine, and Clinical Epidemiology, Toronto Hospital, Ontario, Canada. Source: Naglie, I G Detsky, A S Med-Decis-Making. 1992 Oct-Dec; 12(4): 239-49 0272989X

•

Very low-intensity antithrombotic therapy in atrial fibrillation. Author(s): Danish National Board of Health, Copenhagen, Denmark. Source: Koefoed, B G Petersen, P J-Thromb-Thrombolysis. 1999 January; 7(1): 67-71 09295305

The following information is typical of that found when using the “Full IBIDS Database” to search for “atrial fibrillation” (or a synonym): •

A case of atrial fibrillation with congestive heart failure. Source: Belgrave, J.O.S. Equine-Veterinary-Education (United Kingdom). (1990). volume 2(1) page 2-4. racehorses heart diseases electrocardiography digitalis cardiovascular agents circulatory disorders

Additional physician-oriented references include: •

Anticoagulant therapy for atrial fibrillation. Recommendations from major studies. Author(s): Michigan Heart and Vascular Institute, St Joseph Mercy Hospital, Ann Arbor. Source: Kahn, J K Postgrad-Med. 1992 September 1; 92(3): 119-24, 129-30 0032-5481

•

Anticoagulation in patients with valvular heart disease, atrial fibrillation, or both. Author(s): Department of Medicine, Albert Einstein College of Medicine, Bronx, New York. Source: Kadish, S L Lazar, E J Frishman, W H Cardiol-Clin. 1987 November; 5(4): 591628 0733-8651

Nutrition

107

•

Anticoagulation therapy for atrial fibrillation and coronary disease. Author(s): Yale University School of Medicine, New Haven, Connecticut, USA. Source: Ezekowitz, M D J-Thromb-Thrombolysis. 2000 June; 9 Suppl 1S47-51 0929-5305

•

Antithrombotic therapy for stroke prevention among Medicare beneficiaries hospitalized in Alaska with atrial fibrillation. Author(s): PRO-West/Alaska, Anchorage 99508, USA. Source: Gordian, M E Mustin, H D Alaska-Med. 1998 Oct-December; 40(4): 79-84 00024538

•

Asymptomatic embolisation in non-valvular atrial fibrillation and its relationship to anticoagulation therapy. Author(s): Department of Surgery, Royal Free Hampstead NHS Trust, London, UK. Source: Tinkler, Kerry Cullinane, Marisa Kaposzta, Zoltan Markus, Hugh S Eur-JUltrasound. 2002 June; 15(1-2): 21-7 0929-8266

•

Atrial fibrillation and anabolic steroids. Author(s): Department of Emergency Medicine, Jacobi Medical Center, Bronx, New York, USA. Source: Sullivan, M L Martinez, C M Gallagher, E J J-Emerg-Med. 1999 Sep-October; 17(5): 851-7 0736-4679

•

Atrial fibrillation. Source: Anonymous Harv-Mens-Health-Watch. 1998 April; 2(9): 1-4 1089-1102

•

Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies. Author(s): Department of Medicine (Neurology), University of Texas Health Science Center, San Antonio, TX 78284, USA. Source: Hart, R G Pearce, L A Miller, V T Anderson, D C Rothrock, J F Albers, G W Nasco, E Cerebrovasc-Dis. 2000 Jan-February; 10(1): 39-43 1015-9770

•

Cost-Effectiveness of antiarrhythmic drugs for prevention of thromboembolism in patients with paroxysmal atrial fibrillation. Source: Anonymous Jpn-Circ-J. 2001 September; 65(9): 765-8 0047-1828

•

Development and description of a decision analysis based decision support tool for stroke prevention in atrial fibrillation. Author(s): Department of Epidemiology and Public Health, School of Health Sciences, Newcastle Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. [email protected] Source: Thomson, Richard Robinson, Angela Greenaway, Jane Lowe, Philip QualHealth-Care. 2002 March; 11(1): 25-31 0963-8172

•

Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. Author(s): Department of Medicine, Dalhousie University, Halifax, Nova Scotia, B3K 6A3, Canada. [email protected] Source: Devereaux, P J Anderson, D R Gardner, M J Putnam, W Flowerdew, G J Brownell, B F Nagpal, S Cox, J L BMJ. 2001 November 24; 323(7323): 1218-22 0959-8138

•

Doctors' beliefs on the use of antithrombotic therapy in atrial fibrillation: identifying barriers to stroke prevention. Author(s): are important strategies for targeting barriers to the use of anticoagulation for stroke prevention. Source: Peterson, G M Boom, K Jackson, S L Vial, J H Intern-Med-J. 2002 Jan-February; 32(1-2): 15-23 1444-0903


•

Does lone atrial fibrillation constitute a risk of embolization, and how should we manage it? Author(s): American University Hospital, Beirut, Lebanon. Source: Sawaya, J I J-Med-Liban. 1992; 40(2): 117 0023-9852

•

Effect of low-intensity warfarin therapy on left atrial thrombus resolution in patients with nonvalvular atrial fibrillation: a transesophageal echocardiographic study. Author(s): Second Department of Internal Medicine, Yamaguchi University School of Medicine, Japan. Source: Kimura, M Wasaki, Y Ogawa, H Nakatsuka, M Wakeyama, T Iwami, T Ono, K Nakao, F Matsuzaki, M Jpn-Circ-J. 2001 April; 65(4): 271-4 0047-1828

•

Effects of MgSO4 and glucose, insulin and potassium (GIK) on atrial conduction during the first 12 hours after DC-conversion of chronic atrial fibrillation. Author(s): Department of Cardiology, Lund University, Sweden. Source: Ingemansson, M P Carlson, J PlatoNovember, P Olsson, S B Scand-Cardiovasc-J. 2001 October; 35(5): 340-6 1401-7431

•

Ethnic differences in patient perceptions of atrial fibrillation and anticoagulation therapy: the West Birmingham Atrial Fibrillation Project. Author(s): University Department of Medicine, City Hospital, Birmingham, England. [email protected] Source: Lip, Gregory Y H Kamath, Sridhar Jafri, Marian Mohammed, Afzal Bareford, David Stroke. 2002 January; 33(1): 238-42 1524-4628

•

Idiopathic atrial fibrillation in a champion Standardbred racehorse. Author(s): School of Veterinary Science, University of Melbourne, Parkville, Victoria. Source: Stewart, G A Fulton, L J McKellar, C D Aust-Vet-J. 1990 May; 67(5): 187-91 00050423

•

Impaired exercise-induced vasodilatation in chronic atrial fibrillation--role of endothelium-derived nitric oxide. Author(s): Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan. Source: Takahashi, N Ishibashi, Y Shimada, T Sakane, T Ohata, S Sugamori, T Ohta, Y Inoue, S Nakamura, K Shimizu, H Katoh, H Murakami, Y Circ-J. 2002 June; 66(6): 583-8 1346-9843

•

Improving management of atrial fibrillation and anticoagulation in a community hospital. Author(s): Carney Hospital Anticoagulation Clinic, Boston, USA. Source: Gaughan, G L Dolan, C Wilk Rivard, E Geary, G Libbey, R Gilman, M A Lanata, H Jt-Comm-J-Qual-Improvolume 2000 January; 26(1): 18-28 1070-3241

•

Instability of anticoagulation intensity contributes to occurrence of ischemic stroke in patients with non-rheumatic atrial fibrillation. Author(s): The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan. [email protected] Source: Nozawa, T Asanoi, H Inoue, H Jpn-Circ-J. 2001 May; 65(5): 404-8 0047-1828

•

Intracardiac overdrive pacing as a treatment of atrial flutter in a horse. Author(s): Department of Internal Medicine and Clinical Biology of Large Animal, Faculty of Veterinary Medicine, University of Ghent, Merelbeke, Belgium. Source: Van Loon, G Jordaens, L Muylle, E Nollet, H Sustronck, B Vet-Rec. 1998 March 21; 142(12): 301-3 0042-4900

Nutrition

109

•

Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor? Author(s): Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK. Source: Chung, N A Belgore, F Li Saw Hee, F L Conway, D S Blann, A D Lip, G Y Stroke. 2002 September; 33(9): 2187-91 1524-4628

•

Left atrial and appendage mechanical function after pharmacological or electrical cardioversion in patients with chronic atrial fibrillation: a multicenter, randomized study. Author(s): Emergency Medicine Maggiore Hospital, Italy. Source: Mazzone, C Pandullo, C Scardi, S Salvi, R Miccio, M Cattarini, G Morgera, T ItalHeart-J. 2000 February; 1(2): 128-36 1129-471X

•

Long-term pharmacologic management of atrial fibrillation in the elderly. Author(s): Department of Medicine, Division of Cardiology, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH 44106, USA. [email protected] Source: Waldo, A L Am-J-Geriatr-Cardiol. 2002 Jul-August; 11(4): 233-44; quiz 244-6 1076-7460

•

Long-term prevention of atrial fibrillation after coronary artery bypass surgery: comparison of quinidine, verapamil, and amiodarone in maintaining sinus rhythm. Author(s): Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey. Source: Yilmaz, A T Demirkilic, U Arslan, M Kurulay, E Ozal, E Tatar, H Ozturk, O JCard-Surg. 1996 Jan-February; 11(1): 61-4 0886-0440

•

Mechanisms of cardiac arrhythmias: focus on atrial fibrillation. Author(s): Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Source: Rosen, M R J-Gend-Specif-Med. 2001; 4(3): 37-47 1523-7036

•

Modification of intrinsic AV-nodal properties by magnesium in combination with glucose, insulin, and potassium (GIK) during chronic atrial fibrillation. Author(s): Department of Cardiology, Lund University, Sweden. Source: Ingemansson, M P Carlson, J Olsson, S B J-Electrocardiol. 1998 October; 31(4): 281-92 0022-0736

•

Natural history of atrial fibrillation. Author(s): Department of Cardiology, Heart Institute of Japan, Tokyo Women's Medical College. Source: Hirosawa, K Sekiguchi, M Kasanuki, H Kimata, S Kaneko, N Nakamura, K Aosaki, M Takahashi, S Kondo, M Heart-Vessels-Suppl. 1987; 214-23 0935-736X

•

New antiarrhythmic drugs for the treatment of atrial fibrillation. Author(s): Department of Heart Disease, S. Filippo Neri Hospital, Rome, Italy. [email protected] Source: Castro, A Bianconi, L Santini, M Pacing-Clin-Electrophysiol. 2002 February; 25(2): 249-59 0147-8389

•

Non-rheumatic atrial fibrillation and stroke. Author(s): Austin and Repatriation Medical Centre, Melbourne, Vic. Source: Tonkin, A Aust-N-Z-J-Med. 1999 June; 29(3): 467-72 0004-8291


•

Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation. Author(s): Cardiology Department, Piacenza General Hospital, Piacenza, Italy. Source: Capucci, A Villani, G Q Aschieri, D Rosi, A Piepoli, M F Eur-Heart-J. 2000 January; 21(1): 66-73 0195-668X

•

Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Author(s): Division of Neurology, Department of Medicine, University of Texas. Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7883, USA. [email protected]. Source: Benavente, O Hart, R Koudstaal, P Laupacis, A McBride, R Cochrane-DatabaseSyst-Revolume 2000; (2): CD001927 1469-493X

•

Oral magnesium reduces ventricular ectopy in digitalised patients with chronic atrial fibrillation. Author(s): Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland. Source: Lewis, R V Tregaskis, B McLay, J Service, E McDevitt, D G Eur-J-ClinPharmacol. 1990; 38(2): 107-10 0031-6970

•

Outcomes in the management of atrial fibrillation: clinical trial results can apply in practice. Author(s): Tasmanian School of Pharmacy, Faculty of Health Science, University of Tasmania, Hobart, Australia. Source: Jackson, S L Peterson, G M Vial, J H Daud, R Ang, S Y Intern-Med-J. 2001 August; 31(6): 329-36 1444-0903

•

Paroxysmal atrial fibrillation after high-dose melphalan in five patients autotransplanted with blood progenitor cells. Author(s): Clinica di Ematologia, Universita di Ancona, Italy. Source: Olivieri, A Corvatta, L Montanari, M Brunori, M Offidani, M Ferretti, G F Centanni, M Leoni, P Bone-Marrow-Transplant. 1998 May; 21(10): 1049-53 0268-3369

•

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: I. Reduced flow velocity in the left atrial appendage (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study). Author(s): Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, New York, NY 10029, USA. [email protected] Source: Goldman, M E Pearce, L A Hart, R G Zabalgoitia, M Asinger, R W Safford, R Halperin, J L J-Am-Soc-Echocardiogr. 1999 December; 12(12): 1080-7 0894-7317

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Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence. Author(s): Clinical Services Unit-Pharmaceutical Sciences, Vancouver Hospital and Health Sciences Center, University of British Columbia, Vancouver, BC, Canada. Source: Slavik, R S Tisdale, J E Borzak, S Prog-Cardiovasc-Dis. 2001 Sep-October; 44(2): 121-52 0033-0620

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Pharmacological therapy of atrial fibrillation. Author(s): J.W. Goethe-University, Frankfurt a. M., Germany. Source: Gronefeld, G Bender, B Li, Y G Hohnloser, S H Thorac-Cardiovasc-Surg. 1999 August; 47 Suppl 3334-8 0171-6425

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Plasmin-alpha2-antiplasmin complex in patients with atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators. Author(s): Department of Neurology, The University of Arizona, Tucson, USA. Source: Feinberg, W M Macy, E Cornell, E S Nightingale, S D Pearce, L A Tracy, R P Bovill, E G Thromb-Haemost. 1999 July; 82(1): 100-3 0340-6245

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Platelet P-selectin levels in relation to plasma soluble P-selectin and betathromboglobulin levels in atrial fibrillation. Author(s): Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK. Source: Kamath, Sridhar Blann, Andrew D Caine, Graham J Gurney, David Chin, Bernard S P Lip, Gregory Y H Stroke. 2002 May; 33(5): 1237-42 1524-4628

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Platelets and atrial fibrillation. Author(s): Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK. Source: Kamath, S Blann, A D Lip, G Y Eur-Heart-J. 2001 December; 22(24): 2233-42 0195-668X

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Prescribing patterns for the use of antithrombotics in the management of atrial fibrillation in Zimbabwe. Author(s): [email protected] Source: Bhagat, K Tisocki, K Cent-Afr-J-Med. 1999 November; 45(11): 287-90 0008-9176

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Prevalence of atrial fibrillation and antithrombotic prophylaxis in emergency department patients. Author(s): Department of Emergency Medicine, University of Michigan, Ann Arbor 48109, USA. [email protected] Source: Scott, P A Pancioli, A M Davis, L A Frederiksen, S M Eckman, J Stroke. 2002 November; 33(11): 2664-9 1524-4628

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Safety and effectiveness of oral quinidine in cardioversion of persistent atrial fibrillation. Author(s): Division of Cardiology, Second Idrima Kinonikon Asfaliseon Hospital, N. Plastira 22 N Krini, Thessaloniki, Greece. Source: Kirpizidis, C Stavrati, A Geleris, P Boudoulas, H J-Cardiol. 2001 December; 38(6): 351-4 0914-5087

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Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation? Author(s): Department of Medicine, Guy's, King's & St Thomas' School of Medicine, King's College, London, UK. [email protected] Source: Evans, A Perez, I Yu, G Kalra, L Stroke. 2001 December 1; 32(12): 2828-32 15244628

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Stroke prevention as an indication for the Maze procedure in the treatment of atrial fibrillation. Author(s): Department of Thoracic and Cardiovascular Surgery, Georgetown University Medical Center, Washington, DC 20007, USA. Source: Ad, N Cox, J L Semin-Thorac-Cardiovasc-Surg. 2000 January; 12(1): 56-62 10430679

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Stroke prevention in elderly patients with atrial fibrillation. Author(s): Geriatric Unit, Changi General Hospital, Singapore. [email protected] Source: Lew, S J Lim, J K Singapore-Med-J. 2002 April; 43(4): 198-201 0037-5675


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The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation. Author(s): Department of Cardiology, South Hospital, Sweden. Source: Frick, M Darpo, B Ostergren, J Rosenqvist, M Eur-Heart-J. 2000 July; 21(14): 1177-85 0195-668X

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The morbidity related to atrial fibrillation at a tertiary centre in one year: 9.0% of all strokes are potentially preventable. Author(s): Department of Neurology, The Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, 3050, Australia. [email protected] Source: Evans, A Davis, S Kilpatrick, C Gerraty, R Campbell, D Greenberg, P J-ClinNeurosci. 2002 May; 9(3): 268-72 0967-5868

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The tachycardia-induced dog model of atrial fibrillation. clinical relevance and comparison with other models. Author(s): Department of Pharmacology, Centre for Therapeutic Research, Merck Frosst Canada, 16711 Trans Canada Hwy., Kirkland, Quebec, Canada. [email protected] Source: Gaspo, R J-Pharmacol-Toxicol-Methods. 1999 September; 42(1): 11-20 1056-8719

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The ten most commonly asked questions about stroke prevention in atrial fibrillation. Author(s): The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York 10029-6574, USA. Source: Halperin, J L Cardiol-Revolume 2001 Jul-August; 9(4): 187-92 1061-5377

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Transoesophageal echocardiography-guided cardioversion of atrial fibrillation or flutter. Selection of a low-risk group for immediate cardioversion. Author(s): Department of Cardiology, University Hospital, Lund, Sweden. Source: Roijer, A Eskilsson, J Olsson, B Eur-Heart-J. 2000 May; 21(10): 837-47 0195-668X

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Treatment for atrial fibrillation complications. Author(s): University of Pittsburgh Medical Center, USA. [email protected] Source: Whittle, J Pa-Med. 2000 January; 103(1): 16 0031-4595

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Treatment of atrial fibrillation with warfarin in Rhode Island. Author(s): [email protected] Source: Gifford, D R Silverman, L R Med-Health-R-I. 2000 May; 83(5): 156-7 1086-5462

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Treatment of chronic nonvalvular atrial fibrillation in the elderly: a decision analysis. Author(s): Division of General Internal Medicine, Geriatric Medicine, and Clinical Epidemiology, Toronto Hospital, Ontario, Canada. Source: Naglie, I G Detsky, A S Med-Decis-Making. 1992 Oct-Dec; 12(4): 239-49 0272989X

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Very low-intensity antithrombotic therapy in atrial fibrillation. Author(s): Danish National Board of Health, Copenhagen, Denmark. Source: Koefoed, B G Petersen, P J-Thromb-Thrombolysis. 1999 January; 7(1): 67-71 09295305

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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMD®Health: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND ATRIAL FIBRILLATION Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to atrial fibrillation. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to atrial fibrillation and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “atrial fibrillation” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to atrial fibrillation: •

“Cardioversion” of atrial fibrillation. A report on the treatment of 65 episodes in 50 patients. Author(s): LOWN B, PERLROTH MG, KAIDBEY S, ABE T, HARKEN DE. Source: The New England Journal of Medicine. 1963 August 15; 269: 325-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13931297&dopt=Abstract

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A high-temporal resolution algorithm for quantifying organization during atrial fibrillation. Author(s): Sih HJ, Zipes DP, Berbari EJ, Olgin JE. Source: Ieee Transactions on Bio-Medical Engineering. 1999 April; 46(4): 440-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217882&dopt=Abstract


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A prospective randomized trial of aspirin-clopidogrel combination therapy and doseadjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation. Author(s): Kamath S, Blann AD, Chin BS, Lip GY. Source: Journal of the American College of Cardiology. 2002 August 7; 40(3): 484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142115&dopt=Abstract

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A video-assisted thoracoscopic technique to encircle the four pulmonary veins: a new surgical intervention for atrial fibrillation ablation. Author(s): Manasse E, Infante M, Ghiselli S, Cariboni U, Alloisio M, Barbone A, Addis A, Gallotti R. Source: Heart Surg Forum. 2002; 5(4): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538114&dopt=Abstract

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Analysis of randomness of atrial and ventricular rhythm in atrial fibrillation. Author(s): van den Berg MP, de Langen CD, Haaksma J, Bel KJ, Crijns HJ, Dijk WA, Lie KI. Source: European Heart Journal. 1995 July; 16(7): 971-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7498214&dopt=Abstract

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Anatomy-guided linear atrial lesions for radiofrequency catheter ablation of atrial fibrillation. Author(s): Schwartzman D, Kuck KH. Source: Pacing and Clinical Electrophysiology : Pace. 1998 October; 21(10): 1959-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9793093&dopt=Abstract

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Assessment of global atrial fibrillation organization to optimize timing of atrial defibrillation. Author(s): Everett TH 4th, Moorman JR, Kok LC, Akar JG, Haines DE. Source: Circulation. 2001 June 12; 103(23): 2857-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401945&dopt=Abstract

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Atrial fibrillation during adjuvant chemotherapy with docetaxel: a case report. Author(s): Palma M, Mancuso A, Grifalchi F, Lugini A, Pizzardi N, Cortesi E. Source: Tumori. 2002 November-December; 88(6): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597151&dopt=Abstract

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Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation. Author(s): Jayachandran JV, Sih HJ, Winkle W, Zipes DP, Hutchins GD, Olgin JE.

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Source: Circulation. 2000 March 14; 101(10): 1185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10715267&dopt=Abstract •

Atrial fibrillation. Author(s): BELLET S. Source: Jama : the Journal of the American Medical Association. 1964 August 10; 189: 419-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14162141&dopt=Abstract

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Blood hematocrit changes during paroxysmal atrial fibrillation. Author(s): Imataka K, Nakaoka H, Kitahara Y, Fujii J, Ishibashi M, Yamaji T. Source: The American Journal of Cardiology. 1987 January 1; 59(1): 172-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3812234&dopt=Abstract

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Carotid sinus hypersensitivity and syndrome in patients with chronic atrial fibrillation. Author(s): Cicogna R, Mascioli G, Bonomi FG, Kieval RS, Bernabo MG, Turelli A, Visioli O. Source: Pacing and Clinical Electrophysiology : Pace. 1994 October; 17(10): 1635-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7800566&dopt=Abstract

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Carotid sinus massage in paroxysmal atrial fibrillation. Author(s): SCHWARTZ W. Source: Journal of the American Geriatrics Society. 1960 March; 8: 200-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14444024&dopt=Abstract

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Circadian variation of paroxysmal atrial fibrillation. Author(s): Yamashita T, Murakawa Y, Sezaki K, Inoue M, Hayami N, Shuzui Y, Omata M. Source: Circulation. 1997 September 2; 96(5): 1537-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9315544&dopt=Abstract

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Computer analysis of myocardial tension and pressure variations in atrial fibrillation. Author(s): Mahler Y, Rogel S. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1970 July; 29(1): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4912875&dopt=Abstract

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Conversion of atrial fibrillation to sinus rhythm by carotid sinus massage. Author(s): Ali N, Mills R, Mostaan M. Source: The American Journal of Cardiology. 1984 February 1; 53(4): 652. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6695806&dopt=Abstract


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Conversion of atrial fibrillation to sinus rhythm by direct-current shock. Author(s): ORAM S, DAVIES JP, WEINBREN I, TAGGART P, KITCHEN LD. Source: Lancet. 1963 July 27; 2: 159-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13940259&dopt=Abstract

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DC electroconversion of patients with atrial fibrillation admitted to a coronary care unit. Author(s): Edhag O, Hofvendahl S, Lundman T, Nordlander R, Nyquist O, Sjogren A. Source: Acta Med Scand. 1974 January-February; 1-2(1): 105-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4817077&dopt=Abstract

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Determination of refractory periods and conduction velocity during atrial fibrillation using atrial capture in dogs: direct assessment of the wavelength and its modulation by a sodium channel blocker, pilsicainide. Author(s): Shinagawa K, Mitamura H, Takeshita A, Sato T, Kanki H, Takatsuki S, Ogawa S. Source: Journal of the American College of Cardiology. 2000 January; 35(1): 246-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10636287&dopt=Abstract

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Differential response to carotid sinus pressure during sinus rhythm and atrial fibrillation. Author(s): Hellestrand KJ, Nathan AW, Camm AJ. Source: British Heart Journal. 1982 May; 47(5): 504-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7073915&dopt=Abstract

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Drugs for atrial fibrillation. Digoxin comes from Digitalis lanata. Author(s): Hollman A. Source: Bmj (Clinical Research Ed.). 1996 April 6; 312(7035): 912. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8611904&dopt=Abstract

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Effectiveness and safety of oral verapamil to control exercise-induced tachycardia in patients with atrial fibrillation receiving digitalis. Author(s): Panidis IP, Morganroth J, Baessler C. Source: The American Journal of Cardiology. 1983 December 1; 52(10): 1197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6359848&dopt=Abstract

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Endoscopy-assisted radiofrequency ablation around the coronary sinus ostium in dogs: its effects on atrioventricular nodal properties and ventricular response during atrial fibrillation. Author(s): Tanaka K, Cha YM, Fujimura O. Source: Journal of Cardiovascular Electrophysiology. 1996 November; 7(11): 1063-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8930738&dopt=Abstract


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Epicardial radiofrequency ablation of both atria in the treatment of atrial fibrillation: experience in patients. Author(s): Raman JS, Ishikawa S, Power JM. Source: The Annals of Thoracic Surgery. 2002 November; 74(5): 1506-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440600&dopt=Abstract

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Experience with “cardioversion” of atrial fibrillation and flutter. Author(s): MORRIS JJ Jr, KONG Y, NORTH WC, MCINTOSH HD. Source: The American Journal of Cardiology. 1964 July; 14: 94-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14176899&dopt=Abstract

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External shock therapy for atrial fibrillation. Author(s): GRIFFITHS PD, HUNTSMAN RG, THOMAS CG. Source: British Medical Journal. 1964 January 4; 5374: 53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14071640&dopt=Abstract

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Frequency domain algorithm for quantifying atrial fibrillation organization to increase defibrillation efficacy. Author(s): Everett TH 4th, Kok LC, Vaughn RH, Moorman JR, Haines DE. Source: Ieee Transactions on Bio-Medical Engineering. 2001 September; 48(9): 969-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11534845&dopt=Abstract

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Further experience of electrical conversion of atrial fibrillation to sinus rhythm: analysis of 100 patients. Author(s): ORAM S, DAVIES JP. Source: Lancet. 1964 June 13; 41: 1294-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14149151&dopt=Abstract

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Future directions of electrotherapy for atrial fibrillation. Author(s): Reuter D, Ayers GM. Source: Journal of Cardiovascular Electrophysiology. 1998 August; 9(8 Suppl): S202-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9727698&dopt=Abstract

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High resolution mapping of the pulmonary vein and the vein of Marshall during induced atrial fibrillation and atrial tachycardia in a canine model of pacing-induced congestive heart failure. Author(s): Okuyama Y, Miyauchi Y, Park AM, Hamabe A, Zhou S, Hayashi H, Miyauchi M, Omichi C, Pak HN, Brodsky LA, Mandel WJ, Fishbein MC, Karagueuzian HS, Chen PS. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 348-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875775&dopt=Abstract


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Inhibition of atrial fibrillation by pulmonary vein isolation and auricular resection-experimental study in a sheep model. Author(s): Fieguth HG, Wahlers T, Borst HG. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 1997 April; 11(4): 714-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9151043&dopt=Abstract

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Isolated episodes of atrial fibrillation and acupuncture. Author(s): Celentano A, Palmieri V, Zulati P, Di Minno G. Source: Nutr Metab Cardiovasc Dis. 2003 June; 13(3): 183-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955800&dopt=Abstract

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Knowledge level and coping strategies according to coagulation levels in older persons with atrial fibrillation. Author(s): St-Louis L, Robichaud-Ekstrand S. Source: Nursing & Health Sciences. 2003 March; 5(1): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603723&dopt=Abstract

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Learned control of ventricular rate in patients with atrial fibrillation. Author(s): Bleecker ET, Engel BT. Source: Psychosomatic Medicine. 1973 March-April; 35(2): 161-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4704790&dopt=Abstract

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Lessons learned from computerized mapping of the atrium. Surgery for atrial fibrillation and atrial flutter. Author(s): Ferguson TB Jr, Schuessler RB, Hand DE, Boineau JP, Cox JL. Source: Journal of Electrocardiology. 1993; 26 Suppl: 210-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8189128&dopt=Abstract

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Maintenance of sinus rhythm after conversion of atrial fibrillation and fibrillatory wave rate. Author(s): Aberg H, Nordgren L. Source: Upsala Journal of Medical Sciences. 1973; 78(1): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4702327&dopt=Abstract

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Modeling and closed-loop pharmacologic control of the ventricular rate during induced atrial fibrillation in anesthetized dogs. Author(s): Jannett TC, Kay GN, Crossley GH. Source: Biomed Instrum Technol. 1990 November-December; 24(6): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1979756&dopt=Abstract


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Nonhomogeneous local atrial activity during acute atrial fibrillation: spectral and dynamic analysis. Author(s): Karagueuzian HS, Khan SS, Peters W, Mandel WJ, Diamond GA. Source: Pacing and Clinical Electrophysiology : Pace. 1990 December; 13(12 Pt 2): 193742. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1704571&dopt=Abstract

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On the association between failure in converting atrial fibrillation and fibrillatory wave rate. Author(s): Aberg H, Nordgren L. Source: Upsala Journal of Medical Sciences. 1973; 78(1): 41-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4702328&dopt=Abstract

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P wave polarities of an arrhythmogenic focus in patients with paroxysmal atrial fibrillation originating from superior vena cava or right superior pulmonary vein. Author(s): Kuo JY, Tai CT, Tsao HM, Hsieh MH, Tsai CF, Lin WS, Lin YK, Ding YA, Hou CJ, Tsai CH, Chen SA. Source: Journal of Cardiovascular Electrophysiology. 2003 April; 14(4): 350-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741704&dopt=Abstract

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Paroxysmal atrial fibrillation following marijuana intoxication: a two-case report of possible association. Author(s): Kosior DA, Filipiak KJ, Stolarz P, Opolski G. Source: International Journal of Cardiology. 2001 April; 78(2): 183-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398765&dopt=Abstract

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Paroxysmal atrial fibrillation in a young female patient following marijuana intoxication--a case report of possible association. Author(s): Kosior DA, Filipiak KJ, Stolarz P, Opolski G. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 March-April; 6(2): 386-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208344&dopt=Abstract

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Recognition of digitalis intoxication in the presence of atrial fibrillation: analysis of 167 cases. Author(s): Zhao HY, Feng ZG, Guan SL, Chen MZ. Source: Acta Acad Med Wuhan. 1981; 1(2): 34-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7052261&dopt=Abstract

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Relationship between ventricular rate and cardiac output in mimic experimental atrial fibrillation. Author(s): Liau CS, Chen MF, Lin FY, Tsai CH, Lee YT.


Source: Journal of Electrocardiology. 1994 April; 27(2): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8201300&dopt=Abstract •

Response of atrial fibrillatory activity to carotid sinus massage in patients with atrial fibrillation. Author(s): Bollmann A, Wodarz K, Esperer HD, Toepffer I, Klein HU. Source: Pacing and Clinical Electrophysiology : Pace. 2001 September; 24(9 Pt 1): 1363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584458&dopt=Abstract

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Risk factors associated with development of atrial fibrillation early after coronary artery bypass grafting. Author(s): Cagli K, Gol MK, Keles T, Sener E, Yildiz U, Uncu H, Tasdemir O, Bayazit K. Source: The American Journal of Cardiology. 2000 May 15; 85(10): 1259-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802015&dopt=Abstract

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Robotic atrial septal defect repair and endoscopic treatment of atrial fibrillation. Author(s): Argenziano M, Williams MR. Source: Semin Thorac Cardiovasc Surg. 2003 April; 15(2): 130-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838483&dopt=Abstract

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Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation. Author(s): Brignole M, Gianfranchi L, Menozzi C, Raviele A, Oddone D, Lolli G, Bottoni N. Source: Journal of the American College of Cardiology. 1993 October; 22(4): 1123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8409051&dopt=Abstract

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Spontaneous conversion of long-standing atrial fibrillation. Author(s): Gardner JD, Dunn M. Source: Chest. 1982 April; 81(4): 429-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7067507&dopt=Abstract

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Synchronized counter-shock treatment of atrial fibrillation. a report of twelve cases. Author(s): JONES WL, OGBORN RJ, GUNNARSON R, HILL WA, ORTMEIER DG, RUD PD. Source: S D J Med. 1964 July; 17: 19-25. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14176716&dopt=Abstract

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The effect of drugs and lead maturation on atrial electrograms during sinus rhythm and atrial fibrillation. Author(s): Bump TE, Ripley KL, Guezennec A, Arzbaecher R.


Source: American Heart Journal. 1989 March; 117(3): 577-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2919537&dopt=Abstract •

The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation. Author(s): Frick M, Darpo B, Ostergren J, Rosenqvist M. Source: European Heart Journal. 2000 July; 21(14): 1177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924301&dopt=Abstract

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The treatment of atrial fibrillation by direct current countershock. Author(s): ROBICSEK F, MCCALL M, TAYLOR FH, NAJIB A, SANGER PW. Source: Coll Works Cardiopulm Dis. 1963 April; 66: 501-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14053066&dopt=Abstract

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Thoracoscopic epicardial radiofrequency ablation for vagal atrial fibrillation in dogs. Author(s): Chevalier P, Obadia JF, Timour Q, Bui-Xuan B, Fatemi M, Kirkorian G, Tabib A, Loire R, Touboul P. Source: Pacing and Clinical Electrophysiology : Pace. 1999 June; 22(6 Pt 1): 880-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10392385&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/


The following is a specific Web list relating to atrial fibrillation; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Cardiac Arrhythmia Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements Warfarin Source: Healthnotes, Inc.; www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON ATRIAL FIBRILLATION Overview In this chapter, we will give you a bibliography on recent dissertations relating to atrial fibrillation. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “atrial fibrillation” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on atrial fibrillation, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Atrial Fibrillation ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to atrial fibrillation. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Cardioversion of Atrial Fibrillation: a Novel Approach by Manoharan, Ganesh; Md from Queen's University of Belfast (northern Ireland), 2002, 345 pages http://wwwlib.umi.com/dissertations/fullcit/f721857

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Echocardiographic Assessment of Atrioventricular Plane Displacement: Clinical Application in Patients with Coronary Artery Disease, Atrial Fibrillation and Aortic Stenosis by Rydberg, Erik Gosta Rikard; Dr from Lunds Universitet (sweden), 2003, 120 pages http://wwwlib.umi.com/dissertations/fullcit/f148257

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Emergency Department Treatment of Clinically Stable Paroxysmal Atrial Fibrillation by Kapur, Atul Kumar; Msc from University of Ottawa (canada), 2002, 114 pages http://wwwlib.umi.com/dissertations/fullcit/MQ72772


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Evaluation of New Non-pharmacological Therapies for Symptomatic Atrial Fibrillation: with Special Emphasis on the Maze Procedure by Lonnerholm, Erik Stefan; Phd from Uppsala Universitet (sweden), 2002, 68 pages http://wwwlib.umi.com/dissertations/fullcit/f721617

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Prefiltering for Improved Unknown and Known Source Correlation Detection of Broadband Oscillatory Transients and Predicting the Onset of Paroxysmal Atrial Fibrillation Using Feature Extraction and a Hamming Neural Network by Dean, Marcella Elsener; Phd from University of New Orleans, 2003, 255 pages http://wwwlib.umi.com/dissertations/fullcit/3093162

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The Relationships among Uncertainty, Seriousness of Illness, Social Support, Appraisal of Uncertainty, Health Locus of Control, and Perceived Health Status in Patients Newly Diagnosed with Atrial Fibrillation by Kang, Younhee; Phd from Case Western Reserve University (health Sciences), 2002, 172 pages http://wwwlib.umi.com/dissertations/fullcit/3058837

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND ATRIAL FIBRILLATION Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning atrial fibrillation.

Recent Trials on Atrial Fibrillation The following is a list of recent trials dedicated to atrial fibrillation.8 Further information on a trial is available at the Web site indicated. •

A safety and efficacy trial evaluating the use of SanOrg34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation Condition(s): Atrial Fibrillation Study Status: This study is currently recruiting patients. Sponsor(s): Organon Purpose - Excerpt: This trial will include patients who have a heart condition called atrial fibrillation. Atrial fibrillation is an abnormal rhythm (irregular beat) in the heart. Patients with atrial fibrillation have an increased chance for a blood clot to form in the heart and move to other blood vessels in the body and cause obstruction. This obstruction may damage tissue. For example, a blood clot plugging a vessel in the brain could cause a stroke. Therefore, patients with atrial fibrillation may be given anticoagulant (blood-thinning) tablets such as warfarin or acenocoumarol. The purpose of this study is to compare the safety and effectiveness of a new injectable anticoagulant drug that is administered once weekly, SanOrg34006 (International Nonproprietary Name - idraparinux sodium), with warfarin or acenocoumarol tablets. Assignment to either SanOrg34006 (idraparinux sodium) Injection or vitamin K antagonist (warfarin or acenocoumarol) tablets will be purely by chance and will be known by both patients and their doctors. Phase(s): Phase III Study Type: Interventional

8 These

are listed at www.ClinicalTrials.gov.


Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070655 •

Efficacy and Safety Evaluation of Azimilide or Sotalol vs placebo for Treatment of Patients With Atrial Fibrillation. Condition(s): Atrial Fibrillation Study Status: This study is currently recruiting patients. Sponsor(s): Procter & Gamble Pharmaceuticals Purpose - Excerpt: Atrial fibrillation (abnormal rhythm in the upper chamber of the heart) is a common supraventricular arrhythmia (a type of abnormal heart rhythm) for which antiarrhythmic therapy is often prescribed. The primary goals of therapy are to maintain sinus rhythm (normal heart rhythm) and to reduce the occurrence of episodes of atrial fibrillation. The double-blind, placebo-controlled phase of this study is designed to evaluate the efficacy and safety of oral azimilide compared with placebo and with sotalol, an antiarrhythmic drug, in maintaining sinus rhythm in patients who require cardioversion (electric shock to correct heart rhythm) to correct atrial fibrillation. Once this phase of the study is completed, a second phase with a different study design will be conducted. The second phase is an open-label, follow-up phase to the first study. The follow-up phase will continue to evaluate the long-term safety of a daily oral dose of azimilide in patients who complete the double-blind, placebo-controlled phase of this study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035451

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Efficacy and Safety of Azimilide for the Treatment of Patients With Atrial Fibrillation Condition(s): Atrial Fibrillation Study Status: This study is currently recruiting patients. Sponsor(s): Procter & Gamble Pharmaceuticals Purpose - Excerpt: Atrial fibrillation (abnormal rhythm in the upper chamber of the heart) is a common supraventricular arrhythmia (abnormal heart rhythm) for which antiarrhythmic therapy is often prescribed. The primary goals of therapy are to maintain sinus rhythm (normal heart rhythm) and to reduce the occurrence of episodes of atrial fibrillation. Azimilide may have an effect on increasing the time to first recurrence of symptomatic atrial fibrillation or atrial flutter and symptomatic paroxysmal supraventricular tachycardia (other types of abnormal heart rhythms). This doubleblind, placebo-controlled study is designed to evaluate the efficacy and safety of azimilide compared with placebo in maintaining sinus rhythm in patients who require cardioversion (electric shock to correct heart rhythm) to reduce atrial fibrillation. Once this phase of the study is completed, a second phase with a different study design will be conducted. The second phase is an open-label follow-up phase to the study. This follow-up phase will continue to evaluate the long-term efficacy and safety of a daily oral dose of azimilide in patients who complete the double-blind, placebo-controlled phase of this study. Phase(s): Phase III

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035477 •

Efficacy and Safety of Azimilide in the Prophylactic Treatment of Patients With Atrial Fibrillation. Condition(s): Atrial Fibrillation Study Status: This study is currently recruiting patients. Sponsor(s): Procter & Gamble Pharmaceuticals Purpose - Excerpt: Atrial fibrillation (an abnormal rhythm in the upper chamber of the heart) is a common supraventricular arrhythmia (a type of abnormal heart rhythm) for which antiarrhythmic therapy is often prescribed. The primary goals of therapy are to maintain sinus rhythm (normal heart rhythm) and to reduce the occurrence of episodes of atrial fibrillation. Azimilide may have an effect on increasing the time to first recurrence of symptomatic atrial fibrillation or atrial flutter and symptomatic paroxysmal supraventricular tachycardia (other types of abnormal heart rhythms). This double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of azimilide compared with placebo in prolonging the time to the first symptomatic arrhythmia recurrence in patients with a history of atrial fibrillation and congestive heart failure and/or ischemic heart disease) and those without these conditions. Once this phase of the study is completed, a second phase with a different study design will be conducted. The second phase is an open-label, follow-up phase. The follow-up phase of the study is designed to evaluate the long-term efficacy and safety of a daily oral dose of azimilide in patients who complete the double-blind, placebo-controlled phase of this study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035464

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Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial Condition(s): Heart Disease; Stroke; Ischemic Heart Disease; Myocardial Infarction; Atrial Fibrillation Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to determine which of two treatments, Warfarin or aspirin, is better for preventing death and stroke in patients with poor heart function. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041938


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The Home INR Study Condition(s): Atrial Fibrillation; Mechanical heart valve Study Status: This study is not yet open for patient recruitment. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program Purpose - Excerpt: Since home monitors of prothrombin time (PT) may potentially improve the safety, quality, and convenience of chronic anticoagulation management, it is likely that there will be demands from providers, patients, and manufacturers to make home monitors available to VA patients. The rationale for patient self-testing (PST) is that, compared to conventional high quality anticoagulation management (HQACM), it would permit more intense monitoring and increased patient participation in his/her own care, resulting in increased precision in anticoagulation control and thus fewer events of thromboembolism (strokes) and bleeding. The secondary hypothesis is that PST and HQACM will be comparable in terms of health care utilization and cost. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032591

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “atrial fibrillation” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON ATRIAL FIBRILLATION Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “atrial fibrillation” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on atrial fibrillation, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Atrial Fibrillation By performing a patent search focusing on atrial fibrillation, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.


The following is an example of the type of information that you can expect to obtain from a patent search on atrial fibrillation: •

Apparatus and method for diagnosis and therapy of electrophysiological disease Inventor(s): Anderson; Scott C. (Sunnyvale, CA), Gallup; David A. (Hayward, CA), Pless; Benjamin (Atherton, CA), Richman; Roxanne L. (Los Gatos, CA), Ulstad, Jr.; Jack E. (Boulder Creek, CA), Vaska; Matthias (Palo Alto, CA) Assignee(s): Epicor, Inc. (Sunnyvale, CA) Patent Number: 6,311,692 Date filed: July 19, 1999 Abstract: The invention provides apparatus and methods for mapping conduction pathways and creating lesions in the heart wall for the treatment of atrial fibrillation. The apparatus may include at least one epicardial ablation probe having a plurality of electrodes for creating a lesion. The apparatus and method facilitate the formation of a lesion which electrically isolates the pulmonary veins from the surrounding myocardium. Excerpt(s): This invention relates generally to the diagnosis and treatment of electrophysiological diseases of the heart, and more specifically to devices and methods for epicardial mapping and ablation for the treatment of atrial fibrillation. Atrial fibrillation results from disorganized electrical activity in the heart muscle, or myocardium. The surgical maze procedure has been developed for treating atrial fibrillation and involves the creation of a series of surgical incisions through the atrial myocardium in a preselected pattern so as to create conductive corridors of viable tissue bounded by scar tissue. While very effective in treating atrial fibrillation, the maze procedure is highly invasive, high in moribidity and mortality, and difficult to perform by even the most skilled surgeons. The procedure not only requires a median sternotomy or other form of gross thoracotomy for access to the heart, but requires stopping the heart and establishing cardiopulmonary bypass, to which a significant part of the trauma, morbidity and mortality of the maze procedure may be attributed. As a less invasive alternative to the surgical incisions used in the maze procedure, transmural ablation of the heart wall has been proposed. Such ablation may be performed either from within the chambers of the heart (endocardial ablation) using endovascular devices (e.g. catheters) introduced through arteries or veins, or from outside the heart (epicardial ablation) using devices introduced into the chest through surgical incisions. Various ablation technologies have been proposed, including cryogenic, radiofrequency (RF), laser and microwave. The ablation devices are used to create elongated transmural lesions--that is, lesions extending through a sufficient thickness of the myocardium to block electrical conduction--which form the boundaries of the conductive corridors in the atrial myocardium. Perhaps most advantageous about the use of transmural ablation rather than surgical incisions is the ability to perform the procedure on the beating heart without the use of cardiopulmonary bypass. Web site: http://www.delphion.com/details?pn=US06311692__

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Apparatus and method for treating ventricular tachyarrhythmias Inventor(s): Dreher; Robert D. (Roseville, MN), Gilkerson; James O. (Stillwater, MN), Krig; David B. (Brooklyn Park, MN), Linder; William J. (Golden Valley, MN), Wald; Jan D. (Edina, MN), Zimmer; William L. (Roseville, MN) Assignee(s): Cardiac Pacemakers, Inc. (St. Paul, MN) Patent Number: 6,317,632 Date filed: October 11, 2000 Abstract: A system and method for selectively treating a ventricular tachycardia based on sensed atrial and ventricular intervals from the patient's heart. A detection window of the ten most recent atrial and ventricular intervals are analyzed for the occurrence of either tachycardia or fibrillation. When a majority of the sensed intervals are satisfied, the apparatus starts a duration time interval. Ventricular intervals and atrial intervals are compare, ventricular interval greater than the atrial interval by a bias factor the system delivers tachycardia therapy to the heart. Alternatively, the method withholds tachycardia therapy to the heart when the atrial rate is classified as atrial fibrillation and the ventricular response is unstable. Excerpt(s): The present invention relates generally to implantable pulse generators and in particular to implantable cardioverter-defibrillators for treating ventricular tachyarrhythmias. Implantable cardioverter-defibrillators (ICDs) have evolved significantly since their clinical introduction by Miroski in 1980. Initial ICDs were designed to recognize ventricular fibrillation and to deliver high-energy shocks in an attempt to treat the arrhythmia. However, clinical electrophysiology research indicated that an ICD capable of recognizing and treating ventricular tachycardias as well as ventricular fibrillation was useful for prevention of arrhythmic death. Subsequent ICD development lead to devices that were able to treat ventricular tachycardias with antitachycardia pacing and low-energy cardioversion shocks in conjunction with backup defibrillation therapy. These ICDs monitored the heart rate and the onset of the ventricular arrhythmia from ventricular endocardial signals to determine when the heart was in need either of cardioversion to treat a ventricular tachycardia or of defibrillation to treat ventricular fibrillation. While it was successful in detecting ventricular arrhythmias, the ICDs were unable to reliably discriminate sinus tachycardia and atrial arrhythmias, particularly paroxysmal atrial fibrillation, from malignant ventricular rhythms because of the sole reliance on ventricular cardiac signals to determine the cardiac state. As a result, the ICD might deliver inappropriate therapy based on aberrant ventricular signals that have their origins in an undetected supraventricular tachyarrhythmia, leading to an uncomfortable cardioversion shock being delivered to the patient. Web site: http://www.delphion.com/details?pn=US06317632__

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Atrial branding iron catheter and a method for treating atrial fibrillation Inventor(s): Fuimaono; Kristine B. (Covina, CA), Haissaguerre; Michel (Talence, FR) Assignee(s): Biosense Webster, Inc. (Diamond Bar, CA) Patent Number: 6,371,955 Date filed: August 10, 1999


Abstract: A catheter for ablating tissue comprises a catheter body, a tip section, a branding iron assembly and an infusion tube. The catheter body has an outer wall, proximal and distal ends, and at least one lumen extending therethrough. The tip section comprises a segment of flexible tubing having proximal and distal ends and at least one lumen therethrough. The proximal end of the tip section is fixedly attached to the distal end of the catheter body. The branding iron assembly has proximal and distal ends and is fixedly attached at its proximal end to the distal end of the tubing of the tip section. The branding iron assembly is bent relative to the tubing and comprises a nonretractable tubular electrode formed of a material having shape-memory. The tubular electrode has proximal and distal ends and at least one irrigation port through which fluid can pass from the inside to the outside of the electrode. The infusion tube extends through a lumen in the tip section, with its distal end in fluid communication with the proximal end of the tubular electrode. Excerpt(s): The present invention relates to an improved steerable electrode catheter having an irrigated tip that is particularly useful for treating atrial fibrillation. Atrial fibrillation is a common sustained cardiac arrhythmia and a major cause of stroke. This condition is perpetuated by reentrant wavelets propagating in an abnormal atrial-tissue substrate. Various approaches have been developed to interrupt wavelets, including surgical or catheter-mediated atriotomy. It is believed that to treat atrial fibrillation by radio-frequency ablation using a catheter, continuous linear lesions must be formed to segment the heart tissue. By segmenting the heart tissue, no electrical activity can be transmitted from one segment to another. Preferably, the segments are made too small to be able to sustain the fibrillatory process. A preferred technique for treating atrial fibrillation by radio-frequency ablation would be a "branding iron" approach, where a relatively long electrode can be held stationary in good contact with the heart wall while ablation is completed. In this way, a continuous transmural burn may be effected. U.S. Pat. No. 5,800,428 to Nelson et al. discloses a radio frequency ablation catheter system having a flexible, tubular electrode for creating a continuous linear lesion. The tubular electrode is selectively extendable from the distal end of the catheter. The catheter further comprises mechanisms for remotely manipulating and extending the electrode. However, having an extendable electrode house in the catheter provides less degrees of freedom with respect to the shape, size and length of the tubular electrode. Moreover, the physician has to deal with additional moving and manipulatable parts, adding complexity to the procedure. Further, a retractable electrode can cause contamination because blood or coagulate on the electrode can be pulled into and entrapped inside the catheter. The entrapped coagulate can also affect the ability of the electrode to be further extended and retracted. Accordingly, it would be desirable to provide a catheter design having an electrode for creating linear lesions that overcomes these drawbacks. Web site: http://www.delphion.com/details?pn=US06371955__ •

Atrial sensing and multiple site stimulation as intervention for atrial fibrillation Inventor(s): Mower; Morton M. (Baltimore, MD) Assignee(s): Mower CHF Treatment Irrevocable Trust (Baltimore, MD) Patent Number: 6,337,995 Date filed: November 13, 2000 Abstract: Atrial sensing and stimulation as intervention for atrial fibrillation. The present invention relates to a method of atrial defibrillation using an implanted electronic stimulator. In a variety of protocols varying combinations of conventional and

Patents 137

biphasic stimulation are applied at threshold and sub-threshold levels. In a preferred embodiment, the implantable electronic stimulator of the present invention includes multiple electrodes having stimulating and sensing capabilities. The small size of these electrodes allows for intravenous insertion into the patient. Excerpt(s): The present invention relates generally to electronic stimulation devices to control the beating of hearts, especially hearts with pathologies that interfere with normal rhythmicity, electrical conduction, and/or contractility. In particular, the present invention relates to pacemakers used to overcome atrial fibrillation by use of 1) atrial sensing; 2) electrical test stimulation of the atria; and 3) multiple site stimulation in which the various atrial areas are slowly entrained to a common beating rate to produce electrical/functional conformity, i.e., cardioversion, with each case either eventuating in spontaneous reversion to a normal atrial rhythm, or reduced energy requirement for reversion by electrical countershock. Morbidity associated with malfunctions of the atria, while not immediate, is high. Atrial malfunctions of rhythmicity (e.g., atrial fibrillation, various atrial arrhythmias, A-V block and other conduction abnormalities, etc.) can contribute to thrombosis, emboli, stroke and/or heart failure, each of which can place a patient in significant peril. Atrial Sensing A variety of approaches have been developed which use pacemakers to counter atrial malfunctions of rhythmicity, as well as attendant effects on ventricular function. In addition, sophisticated approaches have been developed for pacemaker systems to determine the nature of any particular ventricular malfunction, and whether a malfunction originates in the atria or in the ventricles. One such approach uses ventricular sensing to measure/determine the probability density function (pdf) on a moment-to-moment basis. For example, U.S. Pat. No. 5,163,429 to Cohen discloses the use of narrow window pdf data as but one criterion among several for assessing ventricular cardiac function. The use of pdf data to determine ventricular fibrillation also is disclosed in Implantable CardioverterDefibrillators (N. A. Estes III, A. Manolis & P. Wang, ed.). U.S. Pat. No. 5,421,830 to Epstein et al. (discussed further below) also discloses the use of pdf data as one set among a variety of data types that collectively are also used to assess cardiac function. The use of probability density function data for assessing atrial cardiac function has not been disclosed and presents its own unique difficulties as will be further discussed. Web site: http://www.delphion.com/details?pn=US06337995__ •

Automated collection and analysis patient care system and method for diagnosing and monitoring the outcomes of atrial fibrillation Inventor(s): Bardy; Gust H. (Seattle, WA) Assignee(s): Cardiac Intelligence Corporation (Seattle, WA) Patent Number: 6,411,840 Date filed: November 16, 1999 Abstract: An automated system and method for diagnosing and monitoring the outcomes of atrial fibrillation is described. A plurality of monitoring sets is retrieved from a database. Each of the monitoring sets include recorded measures relating to patient information recorded on a substantially continuous basis. A patient status change is determined in response to an atrial fibrillation diagnosis by comparing at least one recorded measure from each of the monitoring sets to at least one other recorded measure. Both recorded measures relate to the same type of patient information. Each patient status change is tested against an indicator threshold corresponding to the same type of patient information as the recorded measures which


were compared. The indicator threshold corresponds to a quantifiable physiological measure of a pathophysiology resulting from atrial fibrillation. Excerpt(s): The present invention relates in general to atrial fibrillation (AF) diagnosis and analysis, and, in particular, to an automated collection and analysis patient care system and method for diagnosing and monitoring the outcomes, including cardiovascular consequences, of atrial fibrillation throughout disease onset, progression, regression and status quo. Atrial fibrillation is a heart rhythm abnormality that is one of the leading causes of cardiovascular disease-related morbidity in the world. Clinically, atrial fibrillation involves an abnormality of electrical impulse formation and conduction that originates in the atria, that is, the upper chambers of the heart. Atrial fibrillation can occur in patients with any type of underlying structural heart abnormality, such as coronary artery disease, valvular heart disease, congenital heart disease, and cardiomyopathies of various kinds, thereby complicating patient management and therapy. Further, atrial fibrillation can sometimes occur in patients with no known underlying structural abnormalities or in patients with lung disease or hormonal or metabolic disorders. As well, the occurrence of atrial fibrillation can exacerbate other disorders, for example, myocardial ischemia or congestive heart failure. Effective treatment must include weighing the presence of any comorbidities primary or secondary to atrial fibrillation and whether therapy should be directed against rate control or restoration of normal sinus rhythm. Atrial fibrillation is characterized by multiple swirling wavelets of electrical current spreading across the atria in a disorganized manner. The irregularity of electrical conduction throughout the atria creates irregular impulse propagation through the atrioventricular node into the ventricle and can frequently cause a patient to notice a disturbingly erratic sensation of the heartbeat. These symptoms of an erratic heartbeat, or palpitation, can be trivial or seriously disturbing to the patient's daily functions. Occasionally, the impulse conduction is extremely rapid, leading to reduced diastolic filling of the heart chambers and reduced cardiac pumping action. Rapid heart rate, as well as poor coordination of atrial and ventricular pumping functions, not only lead to a decrease in cardiac output, but also, depending upon the nature of any underlying heart disease, can exacerbate heart failure, coronary blood flow, and pulmonary disorders. Atrial fibrillation may also occur and be totally inconsequential in its cardiovascular and cardiopulmonary consequences or its affect on the patient's quality of life. Yet, even if silent from a cardiovascular and symptom perspective, if persisting beyond a 48 hour period, atrial fibrillation can also result in blood clot formation in the atria, thereby creating the potential for thromboembolism which can lead to strokes or injuries to limbs and major organs. Thus, the outcomes or consequences of atrial fibrillation can be gross or subtle and be rapid or gradual in onset, consequently requiring a range of approaches, from observation to providing emergent interventions. Web site: http://www.delphion.com/details?pn=US06411840__ •

Cardiac rhythm management system promoting atrial pacing Inventor(s): Hartley; Jesse W. (Lino Lakes, MN), Kramer; Andrew P. (Stillwater, MN), Krig; David B. (Brooklyn Park, MN), Stahmann; Jeffrey E. (Ramsey, MN) Assignee(s): Cardiac Pacemakers, Inc. (St. Paul, MN) Patent Number: 6,351,669 Date filed: May 21, 1999

Patents 139

Abstract: A cardiac rhythm management system includes an atrial pacing preference (APP) filter for promoting atrial pacing. The APP filter includes an infinite impulse response (IIR) or other filter that controls the timing of delivery of atrial pacing pulses. The atrial pacing pulses are delivered at an APP-indicated pacing rate that is typically at a small amount above the intrinsic atrial heart rate. For sensed beats, the APP indicated rate is increased until it becomes slightly faster than the intrinsic atrial heart rate. The APP-indicated pacing rate is then gradually decreased to search for the underlying intrinsic atrial heart rate. Then, after a sensed atrial beat, the APP filter again increases the pacing rate until it becomes faster than the intrinsic atrial rate by a small amount. As a result, most atrial heart beats are paced, rather than sensed. This decreases the likelihood of the occurrence of an atrial tachyarrhythmia, such as atrial fibrillation. The decreased likelihood of atrial tachyarrhythmia, in turn, decreases the likelihood of inducing a ventricular arrhythmia, either as a result of the atrial tachyarrhythmia, or as the result of delivering a defibrillation shock to treat the atrial tachyarrhythmia. Excerpt(s): This invention relates generally to cardiac rhythm management systems and particularly, but not by way of limitation, to a cardiac rhythm management system promoting atrial pacing. When functioning properly, the human heart maintains its own intrinsic rhythm, and is capable of pumping adequate blood throughout the body's circulatory system. However, some people have irregular cardiac rhythms, referred to as cardiac arrhythmias. Such arrhythmias result in diminished blood circulation. One mode of treating cardiac arrhythmias uses drug therapy. Drug therapy is not always effective for treating arrhythmias of certain patients. For such patients, an alternative mode of treatment is needed. One such alternative mode of treatment includes the use of a cardiac rhythm management system. Such systems are often implanted in the patient and deliver therapy to the heart. Cardiac rhythm management systems include, among other things, pacemakers, also referred to as pacers. Pacers deliver timed sequences of low energy electrical stimuli, called pace pulses, to the heart, such as via a transvenous leadwire or catheter (referred to as a "lead") having one or more electrodes disposed in or about the heart. Heart contractions are initiated in response to such pace pulses (this is referred to as "capturing" the heart). By properly timing the delivery of pace pulses, the heart can be induced to contract in proper rhythm, greatly improving its efficiency as a pump. Pacers are often used to treat patients with bradyarrhythmias, that is, hearts that beat too slowly, or irregularly. Web site: http://www.delphion.com/details?pn=US06351669__ •

Cardio therapeutic heart sack Inventor(s): Okuzumi; Yuzi (Parker, CO) Assignee(s): Acorn Cardiovascular, Inc. (St. Paul, MN) Patent Number: 6,587,734 Date filed: November 1, 1999 Abstract: This invention relates to implantable heart sack that can be equipped with pacemaker leads and/or defibrillation leads for the treatment of cardiomyopathy, hypertrophic cardiomyopathy, tachycardia, bradycardia, ventricular fibrillation, atrial fibrillation etc. The heart sack was prepared from biocompatible, biostable, implantable polyetherurethane, polycarbonateurethane, silicone, polysiloxaneurethane, polyfluoroethylene, or hydrogenated poly(styrene-butadiene) copolymer. The heart sack is equipped with attached sutures to make it easier to attach onto the heart. The heart sack can be made semipermeable or perforated to have numerous holes. The heart sack


can be reinforced with fiber or filament. Ordinary pacemaker leads can be attached to the inner side of the heart sack. However, the pacemaker leads of this invention were prepared from noble metal (gold, platinum, rhodium and platinum-Rhodium alloys) or stainless steel coated, deposited or plated mono-filaments, yarns, braids, cords, wires or films, or cylindrical tubes of polyamide, polyimide, polyester, and/or polypropylene that are encased in multi-lumen insulating tube or coaxial tube made of biocompatible, biostable, implantable polyetherurethane, polycarbonateurethane, silicone, polysiloxaneurethane, polyfluoroethylene, or hydrogenated poly(styrene-butadiene) copolymer. The leads can be mounted onto the inner surface of the heart sack and contoured to the heart. The heart sack can be coated with hydrophilic coating containing an antimicrobial agent that gives the heart sack a low coefficient of friction, excellent biocompatibility and antimicrobial properties. Excerpt(s): This invention relates to a biocompatible, biostable and implantable heart sack which is prepared from biocompatible, biostable and implantable elastomers selected from the group consisting of polyetherurethane, polycarbonateurethane, silicone, poly(siloxane) urethane and/or hydrogenated poly (styrene-butadiene) copolymer for the treatment of cardiomyopathy, hypertrophic cardiomyopathy, tachycardia, bradycardia, ventricular fibrillation, atrial fibrillation etc. The heart sack of this invention can be reinforced with mono-filaments, yarns, braids, cords, knitted or woven or non-woven cloth made of a biocompatible, biostable, implantable polyamide, polyimide, polyester, polypropylene, and/or polyurethane etc. The heart sack of this invention can be equipped with pacemaker leads and defibrillation leads. The leads and electrodes of this invention are made of noble metal or stainless steel deposited, coated or plated mono-filaments, yarns, braids, cords, wires, films, cloth and/or cylindrical tubes. The noble metal used for this invention is selected from the group consisting of gold, platinum, rhodium and their alloys. The mono-filaments, yarns, braids, cords, wires, films, cloth or cylindrical tubes materials to be coated, deposited or plated with noble metal are selected from the group consisting of poly(ethylene terephthalate), poly(butylene terephthalate), polyamide, polyimide, polypropylene, polyetherurethane, polycarbonateurethane and their copolymers. The heart sack and electrodes are very flexible and have good biocompliance with heart muscle. They have high strength and excellent mechanical properties. Ordinary pacemaker leads and defibrillation leads could be also imbedded into the heart sack to provide cardiac pacing or defibrillation. Electrical therapeutic heart sack devices are a new and noble concept. Cardiomyopathy is a commonly observed disease in an aging population. Cardiomyopathy is a defect of myocardial function. There are three categories of Cardiomyopathies; dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy. Dilated cardiomyopathy refers to a condition in which there is weakened contraction of the ventricles with an apparent dilation of the ventricles. This leads to inadequate perfusion, and increased pulmonary and systemic venous congestion. It will lead essentially to loss of heart function. The history of the disease is one of progressive deterioration. The mortality in one year is greater than 50% for those people who have a poorly functioning heart. Hyper cardiomyopathy is a disease of the heart muscle. It is characterized with an overactive left ventricle due to its increase in muscle mass resulting in an obstruction of the blood that is being pumped from the left ventricle to the rest of the body. This causes dyspnea on exertion and chest pain due to ischemia. Currently, there is no treatment to alter the course of the disease. Restrictive cardiomyopathy is least common of cardiomyopathies. It is due to other pathological processes such as scerderma, amyloid, sarcoid, or storage decease. This invention is to prevent enlargement of the heart and thinning of the heart wall of patients with dilated cardiomyopathy, or hypertrophic cardiomyopathy by the use of a heart sack.

Patents 141

Web site: http://www.delphion.com/details?pn=US06587734__ •

Catheter for treating supraventricular tachyarrhythmias Inventor(s): Hsu; William (Circle Pines, MN), KenKnight; Bruce H. (Maple Grove, MN) Assignee(s): Cardiac Pacemackers, Inc. (St. Paul, MN) Patent Number: 6,430,449 Date filed: December 16, 1999 Abstract: A system and method for treating atrial fibrillation using atrial pacing pulses to convert an atrial fibrillation to non-fibrillation atrial arrhythmia prior to delivering a low energy cardioversion/defibrillation shock. The system and method treats atrial fibrillations by first applying a plurality of pacing pulses to the atria which converts the atrial fibrillation to non-fibrillation atrial arrhythmia. Ventricular intervals are concurrently sensed and analyzed while the plurality of electrical pacing pulses are being applied. Upon detecting a period of stable ventricular intervals, the system then proceeds to deliver a low-energy cardioverting/defibrillating pulse of electrical energy across the atria of the heart. Excerpt(s): The present invention relates generally to implantable medical devices and in particular to implantable electrical pulse generators for treating supraventricular tachyarrhythmias. Effective, efficient ventricular pumping action depends on proper cardiac function. Proper cardiac function, in turn, relies on the synchronized contractions of the myocardium at regular intervals. When the normal cardiac rhythm is initiated at the sinoatrial node, the heart is said to be in sinus rhythm. However, when the heart experiences irregularities in the coordinated contraction of the myocardium, due to electrophysiologic disturbances caused by a disease process or from an electrical disturbance, the heart is denoted to be arrhythmic. The resulting cardiac arrhythmia impairs cardiac efficiency and can be a potential life threatening event. In the supraventricular region of the heart, electrophysiologic disturbances are called supraventricular tachyarrhythmias (SVT). SVT can take several distinguishable forms, including paroxysmal atrial tachycardia, atrial flutter, or atrial fibrillation. SVT are selfsustaining process and may be paroxysmal or chronic. Web site: http://www.delphion.com/details?pn=US06430449__

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Compounds for treatment of cardiac arrhythmia synthesis, and methods of use Inventor(s): Druzgala; Pascal (Santa Rosa, CA), Milner; Peter G. (Los Altos Hills, CA) Assignee(s): Aryx Therapeutics (Los Altos Hill, CA) Patent Number: 6,316,487 Date filed: October 6, 2000 Abstract: The subject invention pertains to novel compounds, and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns a method of making the novel compounds. The novel compounds are rapidly metabolized analogs of amiodarone, having the distinct and advantageous characteristic of being metabolized to a less lipophilic compound. The new compounds can have particular utility for treating life-threatening ventricular tachyarrhythmias, especially in patients with congestive heart failure (CHF). The


product can also provide effective management for ventricular arrhythmias and supraventricular arrhythmias, including atrial fibrillation and re-entrant tachyarrhythmias involving accessory pathways. Excerpt(s): Congestive heart failure (CHF) is a disease affecting approximately 2% of the population of the United States (Sami, M. H. [1991] J. Clin. Pharmacol. 31:1081). Despite advances in the diagnosis and treatment of CHF, the prognosis remains poor with a 5year mortality rate higher than 50% from the time of diagnosis (McFate Smith, W. [1985] Am. J. Cardiol. 55:3A; McKee, P. A., W. P. Castelli, P. M. McNamara, W. B. Kannel [1971] N. Engl. J. Med. 285:1441). In patients with CHF, the rate of survival is lowest in those patients with severe depression of left ventricular function and patients who have frequent ventricular arrhythmias. Patients with ventricular arrhythmias and ischemic cardiomyopathy have an increased risk of sudden death. The presence of ventricular tachycardia in patients with severe CHF results in a three-fold increase in sudden death compared to those without tachycardia (Bigger, J. T., Jr. [1987] Circulation 75(suppl.IV):28). Because of the high prevalence of sudden unexpected death in patients with CHF, there has been a growing interest in the prognostic significance of arrhythmias in these patients. Several compounds have been used in the management of cardiac arrhythmias in patients with congestive heart failure. Unfortunately, antiarrhythmic drug therapy has been disappointing. The efficacy of antiarrhythmic drugs markedly decreases as left ventricular function declines, such that only a small fraction of patients with CHF are responsive to antiarrhythmic therapy. No antiarrhythmic drug has prevented sudden death in patients with CHF. There is even a question of increased mortality associated with certain antiarrhythmic drugs (the CAST investigators [1989] N. Engl. J. Med. 321:406). Scientists define tachycardia and ventricular fibrillation as being of multiple nature. It now seems clear, and is accepted in the art, that re-entry is the underlying mechanism to most sustained arrhythmias. Prolonging ventricular repolarization as a means of preventing ventricular arrhythmias has consequently received renewed attention. This points to Class-III agents as drugs of choice in the treatment of arrhythmias. A Class-III agent, as referred to herein, is an agent which is classified as such in the Vaughan-Williams classification of antiarrhythmic drugs. A Class-III agent exerts its primary antiarrhythmic activity by prolonging cardiac action potential duration (APD), and thereby the effective refractory period (ERP), with no effect on conduction. These electrophysiological changes, which are brought about by blockade of cardiac potassium channels, are well known in the art. Because the blockade of cardiac potassium channels is not associated with depression of the contractile function of the heart, Class-III agents are particularly attractive for use in patients with CHF. Unfortunately, the existing Class-III agents are limited in their utility by additional pharmacological activities, lack of good oral bioavailability, or a poor toxicity profile. The only two Class III agents currently marketed are bretylium (i.v. only) and amiodarone (i.v. and p.o.). Web site: http://www.delphion.com/details?pn=US06316487__ •

Device for the transvenous cardioversion of atrial fibrillation or atrial flutter including three coil electrodes Inventor(s): Michel; Ulrich (Kaiserslautern, DE) Assignee(s): Cardiac Pacemakers, Inc. (St. Paul, MN) Patent Number: 6,438,416 Date filed: March 20, 2000

Patents 143

Abstract: A transvenous catheter for the cardioversion of atrial fibrillation or atrial flutter and/or the stimulation of the heart's activity. The catheter has an electrically active section within a heart and an electrically passive section carrying electrical cables. At least two defibrillation electrodes are located in the electrically active section and coupled to the electrical cables of the catheter. Additionally, there are at least one sensing ring electrode positioned between the at least two defibrillation electrodes and coupled to the electrical cables. Excerpt(s): The present invention relates generally to implantable medical devices and in particular to an implantable transvenous catheter as well as an analysis, pacemaker and/or defibrillation unit. A disorder having a rapid, irregular sequence of heart beats resulting from a disordered electrical excitation of the atria, is known as atrial fibrillation or atrial flutter. A distinction is made between paroxysmal (sudden) and persistent (chronic) arrhythmia. Some of these arrhythmia types may be treated by medications while others must be treated by external cardioversion. For this latter treatment, a high quantity of energy is output through the external area of the body, conventionally under anesthetic to restore the normal cardiac rhythm (sinus rhythm). Several studies have managed to show that the transvenous cardioversion of atrial fibrillation and/or atrial flutter can be performed with a considerably lower energy level than if the energy is applied to the external area of the body. The use of an energy quantity of 200 J in an initial phase of treatment for external cardioversion and, in the event of its failure, two further pulses of 360 J, is proposed by Gordon A. Ewy as the optimal form of therapy in his article entitled "Optimal Technique for Electrical Cardioversion of Atrial Fibrillation", Circulation, pp. 1645 ff, Volume 86, No. 5, November 1986. Despite these high levels of energy output, Ewy emphasizes that great care must be given to ensuring the correct positioning and low transfer resistance of the external defibrillation electrodes, to achieve the best results. Web site: http://www.delphion.com/details?pn=US06438416__ •

Drug bolus delivery system Inventor(s): Christiansen; Chris C. (Oakdale, MN), Lent; Mark (Brighton Park, MN), Robinson; Reginald D. (Plymouth, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,635,049 Date filed: April 30, 1999 Abstract: An bolus delivery system includes an implantable pump, a sensor for sensing an adverse patient condition, such as atrial fibrillation, and a catheter for delivery of a bolus of drug to a target area of a living body. The pump is provided with a bolus metering assembly which includes, in a preferred embodiment, an auxiliary bellows defining a bolus reservoir in addition to the main reservoir of the pump. The auxiliary bellows is selectively placed in fluid communication with the pressurized main supply of drug via an inlet valve to refill the bolus reservoir. An outlet valve is provided to permit egress of the bolus to the catheter from the bolus reservoir. A drive train including a stepper motor and a face cam selectively opens and closes the inlet and outlet valves to effect accumulation or metering and delivery of the bolus. The auxiliary bellows is preferably provided as a collapsible element resiliently biased to an expanded position and is collapsed under pressure in the main reservoir to expel the bolus.


Excerpt(s): The present invention relates to implantable devices for delivering beneficial agents or drugs to a living body. More particularly, the present invention relates to implantable devices for metering and delivering a drug bolus to a target area in a living body in response to sensed adverse patient conditions. Cardiac arrhythmias, which are irregularities in cardiac rhythms, adversely affect millions of individuals. Atrial fibrillation is likely the most common cardiac arrhythmia and may result in dizziness, weakness and other adverse effect. Moreover, atrial fibrillation, may result in death if it leads to ventricular fibrillation. Accordingly, significant efforts have been undertaken to provide therapy to prevent or relieve atrial fibrillation. Such efforts have included drug therapy, in the form of oral or intravenous drugs, and electrical defibrillation techniques. Implantable systems are known for detecting the onset of fibrillation and providing a patient with electronic countermeasures. For example, U.S. Pat. No. 5,817,131, which is incorporated herein by reference in its entirety, discloses an implantable atrial defibrillators which includes implements for monitoring electrical activity of the heart and providing cardioversion countermeasures as well as pain relief therapy to the central nervous system in response to detection of the onset of atrial fibrillation or other adverse conditions. Web site: http://www.delphion.com/details?pn=US06635049__ •

Heart stimulation device with electrotonic inhibition Inventor(s): Gaggini; Guido (Milan, IT), Garberoglio; Bruno (Turin, IT), Marcelli; Emanuela (Macerata, IT), Plicchi; Gianni (Bologna, IT) Assignee(s): Sorin Biomedica Cardio S.p.A. (Saluggia, IT) Patent Number: 6,493,585 Date filed: May 10, 2001 Abstract: Electrodes can generate electrical stimulation pulses at least one first intensity level and at least one second intensity level. The first and second intensity levels are above and below a given stimulation threshold, respectively. The synchronous or asynchronous delivery of second-level pulses enables the conduction of the atrioventricular node to be modulated by electrotonic effect, for example, to reduce ventricular frequency in the event of atrial fibrillation. Excerpt(s): The present invention relates to a device and a method for electrical stimulation of the heart. Experimental studies on animals and on man (such as those reported, for example, in the work "Electronic inhibition and active facilitation of excitability in ventricular muscle" by J. M. Davidenko, M. Delnar, and J. Beaumont in J. Cardiov. Electrophysiol. Vol. 5, No. 11 November 1994, pages 945-960), have shown the effects of subthreshold electrical stimuli on response to subsequent stimulations. These effects are referred to briefly by the term electrotonic inhibition. According to this research, the introduction of a subthreshold conditioning stimulus between two abovethreshold stimulations is followed by a transitory decay in the excitability of the muscle stimulated. In particular, a subthreshold stimulus triggered a certain period of time before the subsequent above-threshold stimulus may delay the response to the subsequent stimulus in question, increasing so-called latency, that is, the interval between the pulse and the respective rapid front of the action potential, and even having an actual inhibition effect. The degree of inhibition is directly proportional to the amplitude and to the duration of the subthreshold conditioning stimulus and is inversely proportional to the post-conditioning period between the electrotonic inhibition pulse and the next stimulation pulse. Electrotonic inhibition can explain some

Patents 145

phenomena which occur during atrial fibrillation in man. This applies in particular to the paradoxical effect of a reduction in ventricular frequency due to the action of a vagotonic drug such as digitalis (which reduces atrial refractory periods and therefore considerably increases the frequency of local atrial fibrillation) and to the effect observed, also during atrial fibrillation, of a reduction in the shortest R-R periods of the electrocardiograph signal, to the point of disappearance, when the ventricle is stimulated at longer intervals. Web site: http://www.delphion.com/details?pn=US06493585__ •

Implantable ventricular cadioverter-defibrillator employing atrial pacing for preventing a trial fibrillation form ventricular cardioversion and defibrillation shocks Inventor(s): Kroll; Mark W. (Simi Valley, CA) Assignee(s): Pacesetter, Inc. (Sylmar, CA) Patent Number: 6,442,426 Date filed: December 1, 1999 Abstract: An implantable ventricular cardioverter/defibrillator applies a quantity of electrical energy to a heart for terminating a ventricular arrhythmia while preventing the induction of atrial fibrillation. The cardioverter/defibrillator includes a ventricular arrhythmia detector and an atrial pacer that delivers atrial pacing pulses to an atrium of the heart when the ventricular arrhythmia detector detects a ventricular arrhythmia. A generator applies a quantity of electrical energy to the heart in timed relation to a delivered atrial pacing pulse to terminate the ventricular arrhythmia to avoid inducing atrial fibrillation. Excerpt(s): The present invention generally relates to an implantable ventricular cardioverter/defibrillator. The present invention more particularly relates to such a cardioverter/defibrillator which employs atrial pacing for preventing the induction of atrial fibrillation from ventricular cardioversion and defibrillation shocks. Extremely high-energy shocks cardiovert or defibrillate the entire heart so as to cardiovert or defibrillate both. the atria and the ventricles to thus preclude induction of atrial fibrillation during ventricular cardioversion or defibrillation. However, the modern trend is to employ more moderate energy shocks for ventricular cardioversion and defibrillation. These energy levels may not cardiovert or defibrillate the atria during ventricular cardioversion and defibrillation. thus frequently the atria in fibrillation after ventricular cardioversion or defibrillation. The induction of atrial fibrillation by ventricular arrhythmia shock therapy causes a cascading sequence of unfortunate problems. The delivery of the ventricular shock usually occurs during a period of patient unconsciousness and is not felt. However, after atrial fibrillation is induced, the patient is left with significant anxiety that there is still an arrhythmia. This can lead to inappropriate decisions on the part of the patient, as well as the implantable ventricular cardioverter/defibrillator. For example, the implanted device can mistake the atrial fibrillation for a ventricular arrhythmia and thus cause another shock to be delivered to the patient. This second shock is often extremely painful, because the patient will now be conscious. The second delivered shock, moreover, will most likely merely serve to ensure that the patient remains in atrial fibrillation. Web site: http://www.delphion.com/details?pn=US06442426__


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Linear ablation assembly Inventor(s): Schaer; Alan K (San Jose, CA) Assignee(s): Cardima, Inc. (Fremont, CA) Patent Number: 6,302,880 Date filed: October 29, 1998 Abstract: An intravascular device for the formation of linear lesions which has particular utility in the treatment of atrial fibrillation and flutter. The intravascular device has an outer delivery member with a distal section which has an elongated opening and a support element coextending with the opening. An EP device having a plurality of electrodes on its distal section is slidably disposed within the inner lumen of the delivery member but it is secured by its distal end within the distal extremity of the delivery member at least while in operation. In this manner an axial force in the proximal direction on the proximal extremity of the EP device, which extends out of the patient during the procedure, will cause the distal shaft section of the EP device to arch outwardly out of and away from the distal section of the delivery shaft along an inner side of the curved distal section and engage the surface of the patient's heart chamber. RF electrical energy delivered to the electrodes on the distal shaft section of the EP device will form a linear lesion which terminates the fibrillation or flutter. Excerpt(s): This invention generally relates to the detection and elimination of cardiac arrhythmia and particularly atrial fibrillation. Atrial fibrillation is the disorganized depolarization of a patient's atrium with little or no effective atrial contraction. This condition may be chronic or intermittent, and it presently affects approximately 2 million or more people in the United States alone. For atrial fibrillation refractory to conventional drug therapy, it has been conventional practice to make incisions in the atrial wall, to surgically segregate the tissue thereof, to discontinue the atrial fibrillation. The atrial segments formed by the surgical segregation are electrically isolated and too small to allow the fibrillation to continue. However, the surgical technique is quite traumatic and is unacceptable to a large fraction of those patient's experiencing atrial fibrillation or flutter. Avitall in U.S. Pat. No. 5,487,385 discloses the use of high frequency electrical energy with a specific intravascular electrophysiological (EP) device to form linear ablations within a patient's atrial chamber to provide results similar to the surgical techniques in terminating atrial fibrillation but with significantly reduced trauma. However, the Avitall device cannot be readily placed within the patient's atrial chamber and provide the necessary contact between the electrodes on the device and the atrial tissue to generate linear lesions of a requisite length when RF electrical energy is emitted from the electrodes. What has been needed is an ablation assembly which can be readily manipulated within a patient's atrial chamber to generate effective linear lesions at any desired location within the atrial chamber. The present invention satisfies these and other needs. Web site: http://www.delphion.com/details?pn=US06302880__

Patents 147

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Method and apparatus for displaying information retrieved from an implanted medical device Inventor(s): Blowers; Paul (St. Paul, MN), Dirnberger; Denise (Blaine, MN), Jamar; Pamela (Plymouth, MN), Ousdigian; Kevin T. (St. Paul, MN), Stone; Karen A. (White Bear Lake, MN), Webb; James D. (Maple Grove, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,583,796 Date filed: December 14, 2000 Abstract: A graphical user interface is provided controllably displaying information retrieved from an implantable device, such as a pacemaker. The graphical user interface is comprised of a first and second window. The first window is adapted to display data identifying a plurality of episodes recorded by the implantable device, wherein the data is comprised of a plurality of fields. One of the fields may be used to identify a type of episode, such as ventricular tachycardia (VT), atrial and ventricular tachycardia (A&V), atrial fibrillation (AF), atrial flutter (Afl), atrial tachycardia (AT), and premature atrial contraction (PAC). The second window is adapted to display data types, such as VT, A&V, AF, Afl, AT, and PAC, that may be present in the plurality of fields, wherein at least one of the data types may be selected to filter the episodes displayed in the first window and display those episodes having the selected data types. Excerpt(s): This invention relates generally to a method and apparatus for displaying data, and, more particularly, to a method and apparatus for displaying data related to cardiac episodes, which have been recorded by an implanted medical device. Since the introduction of the first implantable pacemakers in the 1960s, there have been considerable advancements in both the field of electronics and medicine, such that there is presently a wide assortment of commercially available body-implantable electronic medical devices. The class of implantable medical devices now includes pacemakers, implantable cardioverters, defibrillators, neural stimulators, and drug administering devices, among others. Today's state-of-the-art implantable medical devices are vastly more sophisticated and complex than early ones, capable of performing significantly more complex tasks. The therapeutic benefits of such devices have been well proven. As the functional sophistication and complexity of implantable medical device systems have increased over the years, it has become increasingly useful to include a system for facilitating communication between one implanted device and another implanted or external device, for example, a programming console, monitoring system, or the like. Shortly after the introduction of the earliest pacemakers, it became apparent that it would be desirable for physicians to non-invasively obtain information regarding the operational status of the implanted device, and/or to exercise at least some control over the device, e.g., to turn the device on or off or adjust the pacing rate, after implant. As new, more advanced features have been incorporated into implantable devices, it has been increasingly useful to convey correspondingly more information to/from the device relating to the selection and control of those features. Web site: http://www.delphion.com/details?pn=US06583796__


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Method and apparatus for dual chamber bi-ventricular pacing and defibrillation Inventor(s): Alt; Eckhard (Ottobrunn, DE), Sanders; Richard (Houston, TX), Stotts; Lawrence J. (Lake Jackson, TX) Assignee(s): Intermedics, Inc. (St. Paul, MN) Patent Number: 6,370,427 Date filed: July 23, 1998 Abstract: Device and method are disclosed in which leads with pacing and defibrillating electrodes are implanted into both the right and left ventricles of a patient's heart to enable simultaneous pacing of both ventricles to reduce the width of the QRS complex of the patient's cardiac activity to a more normal duration, and, when appropriate, to apply electrical shock waveforms to both ventricles simultaneously for lower energy defibrillation of the ventricles. In applying the defibrillation therapy, the defibrillating electrode in the left ventricle may be used as the anode and the defibrillating electrode in the right ventricle may be used as the cathode, or both ventricular defibrillating electrodes may be the anode and the metal case in which the shock waveform generator is implanted may be the cathode. Implanting a lead with pacing and defibrillating electrodes in the right atrium enables selective pacing and defibrillation of the atria, in which atrial fibrillation is treated by applying the shock waveform across the right atrial and left ventricular defibrillation electrodes. Excerpt(s): The present invention relates generally to implantable medical devices for treating cardiac dysrhythmias, and more particularly to a multi-mode device which is adapted to provide bi-ventricular therapy to the patient's heart in response to sensing applicable dysrhythmias. Progress in medicine is based largely on progress in the technology of devices and apparatus for administering therapy. For example, significant advances in design techniques that have resulted in continuing reductions in the size of implantable defibrillators, including size of the function generator itself as well as in the heart leads associated therewith, have led to a capability to implant defibrillators at considerably lower risk to patients. During the first few years following the advent of implantable defibrillators, implant procedures required general anesthesia and thoracotomy, and the patient was faced with all of the risks associated with opening the chest cavity. The mortality rate of the procedure tended to limit widespread use of the device. In recent years, with lower defibrillation thresholds (DFTs) and reduction in high voltage capacitor and battery sizes, smaller and more easily implantable devices have been developed, which have allowed this operation to be performed today under only local anesthesia. Smaller diameter and more easily inserted transvenous lead systems have overcome the need for a thoracotomy, and mortality associated with the procedure has been concomitantly reduced to less than one percent. The cosmetic aspects of such an implantation have also improved, with device size and weight allowing it to be implanted in the pectoral region that had previously been reserved for devices capable of only pacing functions, rather than the lower abdomen. Web site: http://www.delphion.com/details?pn=US06370427__

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Method and device for performing cooling- or cryo-therapies for, e.g., angioplasty with reduced restenosis or pulmonary vein cell necrosis to inhibit atrial fibrillation Inventor(s): Dobak, III; John D. (La Jolla, CA), Kramer; Hans W. (Temecula, CA), Yon; Steve A. (San Diego, CA) Assignee(s): Innercool Therapies, Inc. (San Diego, CA) Patent Number: 6,602,276 Date filed: March 21, 2001 Abstract: The present invention provides an enhanced method and device to inhibit or reduce the rate of restenosis following angioplasty or stent placement. The invention involves placing a balloon tipped catheter in the area treated or opened through balloon angioplasty immediately following angioplasty. The balloon, which can have a dual balloon structure, may be delivered through a guiding catheter and over a guidewire already in place from a balloon angioplasty. A fluid such as a perfluorocarbon may be flowed into the balloon to freeze the tissue adjacent the balloon, this cooling being associated with reduction of restenosis. The catheter may also be used to reduce atrial fibrillation by inserting and inflating the balloon such that an exterior surface of the balloon is in contact with at least a partial circumference of the portion of the pulmonary vein adjacent the left atrium. Excerpt(s): Balloon angioplasty, or the technology of reshaping of a blood vessel for the purpose of establishing vessel patency using a balloon tipped catheter, has been known since the late 1970's. The procedure involves the use of a balloon catheter that is guided by means of a guidewire through a guiding catheter to the target lesion or vessel blockage. The balloon typically is equipped with one or more marker bands that allow the interventionalist to visualize the position of the balloon in reference to the lesion with the aid of fluoroscopy. Once in place, i.e., centered with the lesion, the balloon is inflated with a biocompatible fluid, and pressurized to the appropriate pressure to allow the vessel to open. Typical procedures are completed with balloon inflation pressures between 8 and 12 atmospheres. A percentage of lesions, typically heavily calcified lesions, require much higher balloon inflation pressures, e.g., upward of 20 atmospheres. At times, the balloon inflation procedure is repeated several times before the lesion or blockage will yield. The placement of stents after angioplasty has become popular as it reduces the rate of restenosis. Restenosis refers to the renarrowing of the vascular lumen following vascular intervention such as a balloon angioplasty procedure or stent insertion. Restenosis is clinically defined as a greater than 50% loss of initial lumen diameter. The mechanism or root causes of restenosis are still not fully understood. The causes are multifactorial, and are partly the result of the injury caused by the balloon angioplasty procedure and stent placement. With the advent of stents, restenosis rates have dropped from over 30% to 10-20%. Recently, the use and effectiveness of low-dose radiation administered intravascularly following angioplasty is being evaluated as a method to alter the DNA or RNA of an affected vessel's cells in the hope of reducing cell proliferation. Web site: http://www.delphion.com/details?pn=US06602276__


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Method and system for preventing atrial fibrillation by rapid pacing intervention Inventor(s): Boute; Willem (Dieren, NL) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,650,938 Date filed: April 27, 2001 Abstract: A method of pacing cardiac tissue using an implantable medical device is provided. A first fibrillation-indicative interval is determined based on a first fibrillation-indicative event. A first adjusted pacing interval, wherein the first adjusted pacing interval is shorter than the first fibrillation-indicative interval, is determined and the cardiac tissue is paced based on the first adjusted pacing interval. If the cardiac tissue is not captured by pacing at the first adjusted pacing interval, an additional fibrillation-indicative interval is determined based on an additional earlier fibrillationindicative event. An additional adjusted pacing interval, wherein the additional adjusted pacing interval is shorter than the additional fibrillation-indicative interval is determined and the cardiac tissue is paced based on the additional adjusted pacing interval. Excerpt(s): The present invention relates to the field of implantable medical devices. More particularly, the present invention relates to cardiac pacing systems that provide a method for preventing atrial fibrillation by rapid pacing intervention. Tachyarrhythmias are episodes of high-rate cardiac depolarizations. Tachyarrhythmias may occur in one chamber of the heart or may be propagated from one chamber to another. Some tachyarrhythmias are sufficiently high in rate to compromise cardiac output from the chamber(s) affected, leading to loss consciousness or death, in the case of ventricular fibrillation or weakness and dizziness in the case of atrial fibrillation. Atrial fibrillation is often debilitating, due to the loss of atrial cardiac output, and may sometimes lead to ventricular fibrillation. Generally, fibrillation may be terminated by administering high energy level cardioversion/defibrillation shocks or pulses until the fibrillation is terminated. For example, in the context of implantable anti-arrhythmia devices, these pulses may be applied by means of large surface area electrodes on or in the chamber to be defibrillated. However, the high energy level pulses are often sufficient to cause pain to the patient. Moreover, in some cases an atrial defibrillation pulse is delivered at an inappropriate time and may cause ventricular arrhythmias. Thus, it would be desirable to prevent or decrease the occurrence of atrial fibrillation. Web site: http://www.delphion.com/details?pn=US06650938__

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Method of treatment and pharmaceutical composition Inventor(s): de Gasparo; Marc (Es Planches, CH), Webb; Randy Lee (Flemington, NJ) Assignee(s): Novartis AG (Basel, CH) Patent Number: 6,395,728 Date filed: January 9, 2001 Abstract: The invention relates to a method for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, myocardial infarction and its sequelae, supraventricular and ventricular arrhythmias, atrial fibrillation or atrial flutter, atherosclerosis, angina

Patents 151

(whether stable or ustable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetessecondary aldosteronism, primary and secondary pulmonary hyperaldosteronism, primary and pulmonary hypertension, renal failure conditions, such as diabetic nephropathy,glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), and stroke, comprising administering a therapeutically effective amount of combination of (i) the AT.sub.1 -antagonists valsartan or a pharmaceutically acceptable salt thereof and (ii) a Calcium channel blocker or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a mammal in need of such treatment and to corresponding pharmaceutical combination composition. Excerpt(s): (iii) a pharmaceutically acceptable carrier. Valsartan is disclosed in EP 0443983 A. A CCB useful in said combination is preferably selected from the group consisting of amlodipine, diltiazem, felodipine, fendiline, flunarizine, gallopamil, isradipine, lacidipine, mibefradil, nicardipine, nifedipine, niguldipine, niludipine, nimodipine, nisoldipine, nitrendipine, nivaldipine, ryosidine, tiapamil and verapamil, and in each case, a pharmaceutically acceptable salt thereof. All these drugs are therapeutically used as CCBs, e.g. as anti-hypertensive, anti-angina pectoris or antiarrhythmic drugs. Web site: http://www.delphion.com/details?pn=US06395728__ •

Method of using spectral measures to distinguish among atrialfibrillation, atrialflutter and other cardiac rhythms Inventor(s): Reddy; Shankara (Cedarburg, WI), Taha; Basel (Menomonee Falls, WI), Xue; Joel (Germantown, WI) Assignee(s): GE Medical Systems Information Technologies, Inc. (Milwaukee, WI) Patent Number: 6,597,943 Date filed: December 26, 2000 Excerpt(s): The field of the invention relates to cardiac monitoring and more particularly to methods of distinguishing between different types of cardiac abnormalities. Atrial fibrillation (AFIB) and atrial flutter (AFL) are two of the most common abnormal cardiac rhythms, constituting up to 8% of electrocardiograms (ECGs) collected by hospitals. The two rhythms have clinically different implications and require different management. In addition, fibrillatory and flutter waves have different generating mechanisms in the atria. However, these two rhythms are often cross classified by physicians and by computerized ECG analysis systems for two main reasons. First, patterns of atrial flutter and fibrillation often coexist within the same ECG segment examined. The second cause of cross-classification is due to the difficulty of detecting atrial activity (visually or by computer time-based analysis) due to the overlying (and dominant) waveforms of ventricular origin (i.e., the QRS complex and T-wave), especially in the case of high ventricular rates. A method and apparatus are provided for differentiating among atrial-flutter, atrial-fibrillation and other cardiac rhythms. The method includes the steps of estimating a spectral entropy of atrial cardiac activity from an electrocardiogram of a patient and determining that the patient has atrial fibrillation when the spectral entropy is greater than a predetermined value. Web site: http://www.delphion.com/details?pn=US06597943__


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Methods for inducing atrial and ventricular rhythms using ultrasound and microbubbles Inventor(s): Porter; Thomas R. (Omaha, NE), Xie; Feng (Omaha, NE) Assignee(s): The Board of Regents of the University of Nebraska (Lincoln, NE) Patent Number: 6,439,236 Date filed: October 25, 1999 Abstract: A new and improved method for inducing or pacing atrial and ventricular arrhythmias in animals Embodiments of the invention involve using microbubbles enhanced with an insoluble gas in combination with low frequency ultrasound for its pacing activity. The methods and compositions can be used to pace patients, convert patients out of atrial fibrillation, and as a diagnostic to assess a patient's risk for arrhythmias. Excerpt(s): This invention relates to a new and improved method for inducing or pacing atrial and ventricular arrhythmias in animals. The methods and compositions of the invention can be used to pace patients, convert patients out of atrial fibrillation, convert patients with ventricular rhythm disturbances and even as a diagnostic to assess a patients risk for arrhythmias. Normal sinus rhythm of the heart begins with the sinoatrial node (or `SA node`) generating a depolarization wave front. The impulse causes adjacent myocardial tissue cells in the atria to depolarize, which in turn causes adjacent myocardial tissue cells to depolarize. The depolarization propagates across the atria, causing the atria to contract and empty blood from the atria into the ventricles. The impulse is next delivered via the atrioventricular note (or `AV node`) and the bundle of HIS (or `HIS bundle`) to myocardial tissue cells of the ventricles. The depolarization of these cells propagates across the ventricles, causing the ventricles to contract. This conduction system results in the organized sequence of myocardial contraction leading to a normal heartbeat. Web site: http://www.delphion.com/details?pn=US06439236__

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Pulmonary vein ablation stent and method Inventor(s): Keane; David (Wellesley, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 6,632,223 Date filed: March 30, 2000 Abstract: A system for treating atrial fibrillation includes a stent and a delivery catheter for carrying the stent to a treatment site. The stent is self-expanding, for example, being formed of a shape memory alloy, and is configured to lodge against the interior wall of a pulmonary vein. The stent may be formed as a loop, helix, progressively wound helix or other suitable shape, and in one embodiment has an exposed proximal portion including an ablation region that contacts and subtends a circumference of the vein, or contacts endocardial wall tissue along a circumferential path at the ostium. The proximal portion is attached to an energy delivery line in the catheter to energize the stent and ablate tissue in the circumferential region, forming a lesion to block conduction across the ostium or preventing trigger signals originating in the pulmonary vein from initiating or sustaining fibrillation in the atrium. The stent also provides support for the vessel wall, reducing the likelihood of developing pulmonary vein

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stenosis. The stent may also be deployed without concurrent or concomitant ablation, to prevent or treat primary or secondary pulmonary vein stenosis. Excerpt(s): The present invention relates to cardiac treatment, and particularly relates to methods and devices for treating cardiac conditions such as atrial fibrillation. Atrial fibrillation is a common cardiac rhythm disorder which can affect the quality of a patient's life and may be associated with significant morbidity. Atrial fibrillation is characterized by a rapid disorganized rhythm of the upper chambers of the heart (the atria). Instead of a single wavefront of electrical activation during regular rhythm, atria fibrillation consists of multiple coexistent wavefronts with random reentry. The condition may arise following cardiac surgery, or after infection. Its etiology is varied and has even been hypothesized in some cases to have a genetic component. While medication is effective to control fibrillation in some patients, endocardial ablation or surgical intervention is often necessary for effective treatment. Endovascular approaches may be used to create lesions using an ablation catheter to block intraatrial conduction. Surgical procedures such as Cox's maze have been used to address the problem. This procedure creates surgical lines to compartmentalize the tissue of the cardiac wall into a plurality of regions which are each too small to support a depolarization/repolarization cycle. Web site: http://www.delphion.com/details?pn=US06632223__ •

Pulmonary vein arrhythmia diagnostic device and method for use Inventor(s): Altman; Peter A. (South San Francisco, CA) Assignee(s): BioCardia, Inc. (So. San Francisco, CA) Patent Number: 6,577,895 Date filed: October 13, 2000 Abstract: Devices and methods for testing a pulmonary vein to determine whether or not ablation would be effective in terminating atrial fibrillation. The devices and methods include a catheter having an expandable balloon attached to the distal end of the catheter. The balloon has pores on the distal end of the balloon for administering a fluid into the target pulmonary vein. The fluid inhibits the electrical impulses generated by the target pulmonary vein. Once the electrical impulses of the target pulmonary vein have been inhibited it can be determined whether or not the atrial fibrillation continues to occur. If the atrial fibrillation has been eliminated, then ablation or other therapy is appropriate. Thus, the devices and methods limit unnecessary treatment of a pulmonary vein. Excerpt(s): The inventions described below relate to the field of diagnostic medical devices. Specifically the inventions relate to a device and method for diagnosing whether ablation of a portion of the pulmonary vein will eliminate atrial fibrillation originating in the pulmonary vein. Atrial fibrillation (AF) is a form of heart disease that afflicts millions of people. It is a condition in which the normal contraction of the heart is interrupted, primarily by abnormal and uncontrolled action of the atria of the heart. The heart has four chambers: the right atrium, right ventricle, the left ventricle, the left atrium. The right atrium pumps de-oxygenated blood from the vena cava to the right ventricle, which pumps the blood to the lungs, necessary for return flow of deoxygenated blood from the body. The right atrium contracts to squeeze blood into the right ventricle, and expands to suck blood from the vena cava. The left atrium pumps oxygenated blood from the pulmonary veins (returning from the lungs), necessary for


flow of oxygenated blood from the lungs. The left atrium contracts to squeeze blood into the left ventricle, which then pumps the blood into the aorta and thence to the entire body, and expands to suck blood from the pulmonary veins. The contractions of the atria normally occur in a controlled sequence with the contractions of the other chambers of the heart. When the left atrium or the right atrium fails to contract, contracts out of sequence, or contracts ineffectively, blood flow within the heart is disrupted. The disruption of the normal rhythm of contraction is referred to as an arrhythmia. The arrhythmia, known as atrial fibrillation, can cause weakness of the heart due to reduced ventricular filling and reduced cardiac output. Stroke due to clot formation in a poorly contracting atria (which may lead to brain damage and death), and even other life threatening ventricular arrhythmias can also occur. There is a broad spectrum of situations which fall under the broad heading of AF. For example, in older patients where there is substantial heterogeneity in the conduction within the atrial tissue, the patient is said to have the tissue substrate for AF such that any trigger will result in maintaining AF. In younger patients, the tissue may have more homogeneous conduction and be less likely to have sustained AF. In the younger patient it may be the often reoccurrence of a premature depolarizing tissue which acts as a trigger that causes the clinical manifestation of problematic episodes of AF. Clearly, there is a continuous spectrum of degrees of triggered AF and conduction heterogeneity which acts as a substrate for this arrhythmia, and it is appropriate that a number of medical therapies are being developed to treat and diagnose this disease. Web site: http://www.delphion.com/details?pn=US06577895__ •

QRST subtraction using an adaptive template for analysis of TU wave obscured atrial activity Inventor(s): Groenewegen; Arne Sippens (Burlingame, CA), Lesh; Michael D. (Mill Valley, CA), Mlynash; Michael D. (Mountain View, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,615,075 Date filed: March 14, 2001 Abstract: The present invention provides a noninvasive localization, characterization and classification apparatus and method for cardiac arrhythmias. The invention enables discrete isolation of the intricate spatial and temporal detail in morphology of the atrial activity of interest from superimposed ventricular activity of a preceding heartbeat in a particular arrhythmia. An adaptive QRST subtraction template is used that is modulated for discrepancies in voltage and rate between the QRST template and arrhythmia signal. The QRST template modulation is accomplished by using one or more fiducial points and windows that are annotated in both the QRST template and the arrhythmia signal. The invention includes, but is not limited to, the isolation of atrial activity that are commonly known as: (1) P waves in case of focal atrial fibrillation, atrial tachycardia, and orthodromic AV reentrant tachycardia; (2) fibrillation waves in case of chronic atrial fibrillation; and (3) flutter waves in case of atrial flutter. Excerpt(s): This invention relates generally to electrocardiographic localization and classification of cardiac arrhythmias. More particularly, the present invention relates to noninvasive analysis of TU wave obscured atrial activity. An arrhythmia is any deviation from or disturbance of the normal heart rhythm. This is when the heart's natural pacemaker develops an abnormal rate or rhythm (e.g. a tachycardia where the heart rate is faster than normal), the normal conduction pathway is interrupted, an

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abnormal or accessory conduction pathway controls the rhythm, or when another part of the heart takes over as an ectopic pacemaker. Arrhythmias may be benign, life threatening or even fatal depending on the type of arrhythmia. Several different types of arrhythmias can be distinguished, for example atrial tachycardia, atrioventricular (AV) node reentrant tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia. Although electrocardiographic arrhythmia evaluation is currently feasible by capturing spontaneous tachycardia episodes via ambulatory or emergency electrocardiogram (ECG) recording, analysis of the timing and presumed origin of atrial activation on the body surface is frequently hampered by the simultaneous occurrence of the higher voltage ventricular activation or recovery potentials. During both focal and incisional reentrant atrial tachycardia, the low-amplitude P wave (atrial activity) may be obscured by the preceding high-amplitude QRST segment (ventricular activity). Difficulties are encountered when visually assessing the P wave morphology of TU wave superimposed ectopic atrial beats that are critically related to atrial fibrillation triggered by a focal source, typically situated in one of the pulmonary veins. Similarly, localization of the atrial insertion site using the retrograde P wave morphology obtained during orthodromic AV reentrant tachycardia may be difficult due to partial or complete concealment by the TU wave. Web site: http://www.delphion.com/details?pn=US06615075__ •

Regularization of ventricular rate during atrial tachyarrhythmia Inventor(s): Betzold; Robert A. (Fridley, MN), Igel; David A. (Lino Lakes, MN), Kleckner; Karen J. (New Brighton, MN), Markowitz; H. Toby (Roseville, MN), Schroetter; Jeremy A. (Lauderdale, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,434,424 Date filed: December 22, 1999 Abstract: A pacing system provided with a mode switching feature and ventricular rate regularization (VRR) function adapted to stabilize or regularize ventricular heart rate during chronic or paroxysmal atrial tachyarrhythmia. In a preferred embodiment, the pacing system nominally operates in an atrial synchronized pacing mode such as DDD or DDDR pacing mode. In response to detection of atrial rhythm characteristics consistent with an atrial tachyarrhythmia, e.g., atrial fibrillation, a mode switch into a non-atrial synchronized, ventricular rate regularization pacing mode, e.g. DDIR or VDIR pacing mode, is made. If the VRR function is programmed on, the ventricular pacing rate based upon a rate responsive sensor derived ventricular pacing rate modulated on a beat by beat basis by preceding intrinsic or paced ventricular events, the stability of the intrinsic ventricular heart rate, and any atrial pace events to regularize the ventricular pacing rate. The pacing system may also be permanently programmed to the DDIR pacing mode with the VRR feature functioning continuously. The pacing system may also be permanently programmed to the VVIR pacing mode with VRR function activated, but without consideration of atrial pace events. Excerpt(s): This invention relates to the field of external and implantable cardiac pacing systems incorporated into cardiac pacemakers or implantable cardioverter/defibrillators (ICDs), particularly atrial and ventricular synchronous pacing systems, wherein ventricular heart rate is stabilized or regularized during atrial tachyarrhythmias, particularly atrial fibrillation. Episodes of atrial tachyarrhythmias, including atrial fibrillation (AF), are experienced by some heart patients. Although AF episodes may


not be immediately life threatening, they may be associated with extreme symptoms, a reduced quality of life, and a reduced cardiac output. During AF episodes, the ventricular intervals may vary substantially from one ventricular cycle to the next if such patients have intact AV conduction. See R. J. Cohen et al., "Quantitative Model For Ventricular Response During Atrial Fibrillation", IEEE Transactions on Biomedical Engineering Volume 30, pages 769-782 (1983). Ventricular rate irregularity is undesirable because it is uncomfortable for the patient, may increase susceptibility to ventricular tachyarrhythmias, and can decrease cardiac output. Many patients are not symptomatic during AF. However, symptomatic AF patients are typically treated with drugs, e.g., amiodarone, to suppress the AF and maintain sinus rhythm. These "rhythm control" drug therapies are frequently ineffectual and/or have undesirable side effects. Alternatively, physicians prescribe drugs to reduce the ventricular heart rate ("rate control"). In some patients, it is not possible to achieve rate control due to ineffective drugs, side effects, contraindications, or lack of compliance by the patient. Physicians treat patients who fail rhythm control or rate control drug therapies with AV nodal ablation and pacemaker implantation. AV node ablation is undesirable because it causes irreversible destruction of the AV node, results in the patient being pacemaker dependent, and is associated with an increased risk for sudden cardiac death. Web site: http://www.delphion.com/details?pn=US06434424__ •

SINGLE PASS MULTIPLE CHAMBER IMPLANTABLE ELECTRO-CATHETER FOR MULTI-SITE ELECTRICAL THERAPY OF UP TO FOUR CARDIAC CHAMBERS, INDICATED IN THE TREATMENT OF SUCH PATHOLOGIES AS ATRIAL FIBRILLATION AND CONGESTIVE/DILATE CARDIO MYOPATHY Inventor(s): Cammilli; Leonardo (Via G. Caselli 11, 50100 Florence, IT), Grassi; Gino (Via F. Pasqui 31, 50019 Sesto Fiorentino, Florence, IT) Assignee(s): none reported Patent Number: 6,397,109 Date filed: December 29, 1999 Abstract: A single introduction electro-catheter to be used for permanent, semipermanent or termporary cardiac stimulation through the Coronary Sinus. Said electro-catheter featuring the possibility to stimulate from one to four cardiac chambers, according to the preferred stimulation protocol, either in sequence or simultaneously, said catheter being characterized by part or all of the following features.A) A configuration such to be able to support one, two three or four electrodes, placed on separated segments whenever necessary, said electrodes being placed in contact with the targeted cardiac chambers.B) A stent structure is permanently tied to the electrocatheter, in its distal portion close to the electrode bearing portion of said lead.C) The stent structure, and the mated electro-catheter segments will be kept in their compressed form while introduced in the access vein. Such compressed form being of an acceptable diameter for trasvenous introduction.D) Once the system is advanced to the targeted position in the Coronary Sinus, the stent structure will be expanded, dilating the bifurcation of the lead and pushing the electrodes against the cardiac walls.E) A suitable pre-curvature (40.degree. 90.degree.) is intrinsically given to the lead body along its length, so to allow for an easy positioning of the whole structure in the Coronary Sinus, as described in FIG. 2. Excerpt(s): In clinical electro-physiology there is a growing interest for multisite cardiac pacing intended to be used for prevention and/or therapy of such pathologies as Atrial

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Fibrillation (AF) and dilative cardio myopathy (DCM). It has been proven that appropriately timed (sequential and/or simultaneous) somministration of electrical therapy to the different cardiac chambers, up to all four of them, Right Atrium (RA) and Right Ventriculum (RV) and respectively Left Atrium (LA) and Left Ventriculum (LV) can be beneficial to the patients. The appropriate timing of the stimuli shall be chosen according to the appropriate therapy, but it is crucial, to perform such task, that an adequate number of suitable electrical connections be made to every and each heart chamber to be paced and/or defibrillated. In particular, the above said pathologies are, nowadays, considered as the most likely to experience beneficial effects from multi-site pacing, for said reason the following description will be focused on the above said category of cardiac patients, said particularization not being detrimental to the purpose of disclosure of the general principles underlying the present invention. Web site: http://www.delphion.com/details?pn=US06397109__ •

Surgical ablation tool Inventor(s): Carner; David J. (Fremont, CA), Hilario; Reynaldo P. (Sunnyvale, CA), Seraj; Mahmoud K. (Mountain View, CA) Assignee(s): Cardima, Inc. (Fremont, CA) Patent Number: 6,332,881 Date filed: September 1, 1999 Abstract: This is a tool used during open heart or open chest surgery for creating lesions or lines of ablation in tissue to treat atrial fibrillation. It is a relatively short device having a rigid or semi-rigid shaft connected on one end to a handle and on the other end to a more flexible distal tip having one or more electrodes. The distal end of the shaft is angled so to define a first plane of deflection. A deflection mechanism consisting of a pull wire and flat spring housed in a lumen of the tool is manipulable via the handle for deflecting the distal tip in a plane different than the first plane of deflection, allowing direct contact with the curved surface of the tissue, either epicardial or endocardial, to be ablated. The tool may contain fiber optic or other data lines for transmitting data relevant to the patient, and it may be irrigated to cool the tool and the electrodes or to deliver therapeutic fluids to tissue. The tool may also contain temperature sensing device such as a thermocouple or thermistor, which can optionally be configured in a feedback and control system with the irrigation to selectively monitor and control the temperature of the tool or surrounding tissue. Excerpt(s): This invention generally relates to the treatment of cardiac arrhythmia and atrial fibrillation. In particular, this invention is a surgical ablation tool for treating atrial fibrillation by creating lesions in cardiac tissue during open heart or open chest surgery. Atrial fibrillation (AF) is characterized by the irregular and very rapid beating of the heart's atrial chambers and results when the normal electrical conduction system of the atria malfunctions, leading to irregular and chaotic electrical signals. During AF, the regular pumping action of the atria is replaced by irregular, disorganized and quivering spasms of atrial tissue. These spasms may lead to reduced blood flow, blood clots, stroke and even death. This malfunction results in the failure of the atria to fill the ventricles completely and, consequently, the failure of the heart to pump adequate amounts of blood to the body. Once AF becomes symptomatic, it is typically associated with significant morbidity related to reduced blood flow. Often, the greatest concern is that the reduced cardiac output can lead to blood pooling in the atria and the formation of blood clots. Blood clots in the left atrium can dislodge and travel through the


bloodstream to the brain, resulting in stroke and even death. In the United States, AF currently affects an estimated two million people, with approximately 160,000 new cases being diagnosed each year. About 1.5 million outpatient visits and more than 200,000 patient admissions per year in the United States are associated with AF. AF is responsible for over 70,000 strokes each year in the United States alone; the annual cost of treating these patients is more than $3.6 billion. The cost of drug treatment for AF alone is estimated to be in excess of $400 million worldwide each year. Web site: http://www.delphion.com/details?pn=US06332881__ •

Surgical treatment for atrial fibrillation using radiofrequency technology Inventor(s): Wellman; Parris S. (Hillsborough, NJ) Assignee(s): Ethicon, Inc. (Somerville, NJ) Patent Number: 6,585,733 Date filed: September 28, 2001 Abstract: Ablation systems and methods for treating atrial fibrillation utilizing RF energy are provided. The system generally includes a first conductive member having a shape which defines a desired lesion pattern or a portion of a desired lesion pattern, and a second conductive member effective to transmit ablative radiation to the first conductive member. The first conductive member is adapted to be positioned on a first tissue surface, and the second conductive member is adapted to be positioned on a second, opposed tissue surface. In use, ablative radiation is transmitted from the second conductive member through the tissue to the first conductive member to form a lesion having the desired lesion pattern. Excerpt(s): The present invention relates to instruments and methods for treating atrial fibrillation, and more particularly to a surgical instrument and method for ablating cardiac tissue using radiofrequency energy. Cardiac arrhythmias, such as atrial fibrillation, are a commonly occurring disorder characterized by erratic beating of the heart. The regular pumping function of the atria is replaced by a disorganized, ineffective quivering caused by chaotic conduction of electrical signals through the upper chambers of the heart. While medication can be an effective treatment for some cases, many patients are not responsive to medical therapies and require alternative treatment. As an alternative to medication, a surgical technique, known as the Maze technique, requires open chest surgery to strategically incise the atrial wall, and subsequently repair the incisions by suturing. The result of this surgery is to create scar tissue located along the incision lines and extending through the atrial wall to block electrical conductivity from one segment to another. While the Maze procedure has proven effective in restoring normal sinus rhythm, it requires considerable prolongation of cardiopulmonary bypass and aortic crossclamp time, especially when performed in combination with other open heart procedures. Over the last decade, more simplified techniques have been proposed which replace surgical incisions with ablations, or scars, formed in the heart tissue. The various energy sources used in ablation technologies include cryogenic, radiofrequency (RF), laser, and microwave energy. The ablation devices are used to create tissue lesions in an affected portion of the heart in order to block electrical conduction. Web site: http://www.delphion.com/details?pn=US06585733__

Patents 159

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System and a corresponding method for treating defibrillation in a heart Inventor(s): Renirie; Alexis C (Berg en Dal, NL), Schouten; Vincent (Cadier en Keer, NL), Weijand; Koen (Hoensbroek, NL) Assignee(s): Medtronic Inc. (Minneapolis, MN) Patent Number: 6,330,475 Date filed: December 6, 1999 Abstract: There is provided an implanted system and method for delivering subsonic mechanical waves to one or more selected patient areas, said areas including the patient's heart and/or lungs. The mechanical waves are delivered for the purpose of treating fibrillation or like arrhythmias, for enhancing lung gas exchange, enhancing cardiac muscle fiber relaxation, and enhancing coronary perfusion. Mechanical waves are generated in a frequency range of about 1,100,000 Hz, and preferably 1-50,000 Hz. The waves may be delivered continuously for short or long time periods, or may be controlled in timing either with respect to detected portions of a patient's heartbeat signal or in response to a detected event such as fibrillation. In one preferred embodiment, the implantable system includes a defibrillation shock generator and control for responding to a defibrillation event by first delivering a sequence of mechanical waves and then delivering an electrical defibrillation shock. In another embodiment, the system and method treat incipient fibrillation or arrhythmia by delivering mechanical waves of predetermined timing to the patient's heart and/or lungs. In a specific embodiment, mechanical waves are delivered through an array of transducers to the patient's atrial wall, to treat atrial fibrillation. Excerpt(s): The system and method of this invention relate to systems for treating cardiac fibrillation and, in particular, for using transducers driven at frequencies below the ultrasound range for mechanical treatment of the heart and related target areas. Delivery of electrical shocks has proven to be an effective and relatively safe means for defibrillation of the heart, or for treating various types of cardiac arrhythmias. Implantable defibrillators, cardioverters, and combined pacemaker/cardioverter/defibrillator devices have come into widespread use for treatment of various arrhythmias. As effective as these new devices and systems have been, there remain a number of areas where substantial development work is needed, in order to increase efficiency and reliability, and to deal with known adverse effects. Some of the known problem areas are those of tissue damage in the vicinity of the electrodes across which the shocks are delivered, and in the case of atrial defibrillation, the patient sensation of sharp pain which can be caused by over-stimulation of the phrenic nerve. Despite improvements in lead and electrode design, there remains an ongoing need to reduce the amount of energy delivered in a shock, both for purposes of preserving the battery energy in the implanted device and for the important purpose of reducing patient anxiety about receiving a shock. One alternative approach to the area of defibrillation that has been considered but not given much development is using ultrasound for defibrillating. This involves delivering high energy ultrasound waves to the affected region, e.g., the atrium or ventricle. Unfortunately, this technique has thus far met with a low success rate, on the order of 30%, and has been seen to cause damage to the endothelium and to the cardiac muscle fibers. However, it is the basis of this invention that lower frequency mechanical agitation of the heart has a variety of potential beneficial effects which have not yet been successfully exploited, particularly in treating a fibrillating heart or a heart which is prone to fibrillation or other arrhythmias. Mechanical agitation of the heart, particularly at frequencies below about 50 kHz, can have a direct defibrillation effect, as well as other beneficial effects on the


fibrillating heart. Mechanical agitation, or movement of the cardiac muscle with sufficient energy can change the conductive properties of the muscle, and thus change the loop gain and disrupt the circular conductive paths which had been responsible for the fibrillation or other arrhythmia. Likewise, mechanical agitation may affect action potential duration of myocardial cells, and thus aid in termination of fibrillation. Mechanical agitation directed to the cardiac muscle may facilitate muscle fiber relaxation, and help bring the fibers into diastole. This, in turn, can reduce the threshold for electrical defibrillation. Similarly, mechanical treatment may be used to improve cardiac perfusion. It is known that perfusion of the myocardium is limited to the diastolic phase, and that during fibrillation perfusion stops even though the aortic pressure remains high for a few seconds. Application of low frequency mechanical waves to the myocardium can have a relaxing effect which improves perfusion, as well as a direct massaging effect which aids perfusion. Web site: http://www.delphion.com/details?pn=US06330475__ •

System and method for continuously monitoring classified atrial arrhythmias Inventor(s): Chen; Victor (Minnetrista, MN), Eberle; LeAnne (St. Louis Park, MN), Foster; Clayton (Andover, MN), Propp; Hal (Oakdale, MN), Ricci; Carlos (Apple Valley, MN), Seim; Gary (Minneapolis, MN) Assignee(s): Cardiac Pacemakers, Inc. (St. Paul, MN) Patent Number: 6,470,210 Date filed: April 6, 2001 Abstract: Systems and methods are provided for analyzing occurrences of atrial arrhythmias. Occurrences of each of a number of classified atrial arrhythmia rhythms are detected. The classified atrial arrhythmias may, for example, include at least atrial fibrillation and atrial flutter. A duration of time associated with each of the detected atrial arrhythmia rhythms is measured. Trend data is produced with respect to a predetermined period of time using all or selected ones of the measured time durations. The detecting, measuring, and producing processes may also be performed for one or more unclassified atrial arrhythmias. Excerpt(s): The present invention relates generally to implantable medical devices and, more particularly, to implantable pacemakers and cardioverter-defibrillators for continuously monitoring and accurately measuring atrial arrhythmias. Implantable cardioverter-defibrillators (ICDs) have been developed that employ detection algorithms capable of recognizing and treating ventricular tachycardias and ventricular fibrillation. Detection algorithms are also being developed to recognize and treat atrial tachycardias and atrial fibrillation. In general, ICDs are designed to treat such tachycardias with antitachycardia pacing and low-energy cardioversion shocks in conjunction with back-up defibrillation therapy. These ICDs monitor the heart rate and the onset of the arrhythmia by sensing endocardial signals and determining when the heart is in need of either cardioversion to treat a given tachycardia or of defibrillation to treat a fibrillation condition. Certain ICDs have been designed with dual chamber sensing capabilities to detect and analyze both ventricular and atrial endocardial signals. This increase in cardiac signal input to the ICD has provided an opportunity to determine the origin and the nature of atrial and ventricular tachyarrhythmia, and to reduce the frequency of inappropriate therapy being delivered to an implant patient. Web site: http://www.delphion.com/details?pn=US06470210__

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Use of low molecular weight thrombin inhibitor Inventor(s): Gustafsson; David (Kullavik, SE) Assignee(s): AstraZeneca AB (Sodertalje, SE) Patent Number: 6,462,021 Date filed: November 6, 2000 Abstract: According to the invention there is provided the use of melagatran, or a pharmaceutically-acceptable derivative thereof, for the manufacture of a medicament for the treatment of ischemic disorders in patients having, or at risk of, non-valvular atrial fibrillation. Excerpt(s): This invention relates to a new use of the low molecular weight thrombin inhibitor, melagatran and derivatives thereof. Atrial fibrillation (AF) is characterised by grossly disorganised atrial electrical activity that is irregular in respect of both rate and rhythm. Patients with AF have no visually discernible timing pattern in atrial electrical activity when measured by surface ECG, or in electrogram sequences recorded by catheter electrodes. During AF, the regular pumping action of the atria is replaced by irregular, disorganised and quivering spasms of atrial tissue. These spasms may be experienced as irregular heartbeat, palpitations, discomfort, dizziness and/or angina pectoris. Further, the inefficient pumping action of the heart tends to lead to significant morbidity related to reduced blood flow. More seriously, the reduced cardiac output can lead to blood pooling in the left atria and the formation of blood clots. Blood clots, mostly originating in the left atrium, can dislodge as an embolism and travel through the bloodstream to organs, e.g. the brain, spleen, kidneys etc. If the embolism travels to the brain, this may result in cerebral stroke and even death. Web site: http://www.delphion.com/details?pn=US06462021__

Patent Applications on Atrial Fibrillation As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to atrial fibrillation: •

Ablation catheter and method for isolating a pulmonary vein Inventor(s): Flickinger, William J.; (Lino Lakes, MN), Francischelli, David E.; (Anoka, MN), Mehra, Rahul; (Stillwater, MN), Min, Xiaoyi; (Plymouth, MN), Stewart, Mark T.; (Lino Lakes, MN) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030191463 Date filed: April 16, 2003 Abstract: A catheter assembly and method for treatment of cardiac arrhythmia, for example, atrial fibrillation, by electrically isolating a vessel, such as a pulmonary vein, from a chamber, such as the left atrium. The catheter assembly includes a catheter body

10

This has been a common practice outside the United States prior to December 2000.


and at least one electrode. The catheter body includes a proximal portion, an intermediate portion and a distal portion. The intermediate portion extends from the proximal portion and defines a longitudinal axis. The distal portion extends from the intermediate portion and forms a substantially closed loop transverse to the longitudinal axis. The at least one electrode is disposed along the loop. With this configuration, the loop is axially directed into contact with the chamber wall about the vessel ostium. Upon energization, the electrode ablates a continuous lesion pattern about the vessel ostium, thereby electrically isolating the vessel from the chamber. Excerpt(s): The heart includes a number of pathways that are responsible for the propagation of signals necessary to produce continuous, synchronized contractions. Each contraction cycle begins in the right atrium where a sinoatral node initiates an electrical impulse. This impulse then spreads across the right atrium to the left atrium, stimulating the atria to contract. The chain reaction continues from the atria to the ventricles by passing through a pathway known as the atrioventricular (AV) node or junction, which acts as an electrical gateway to the ventricles. The AV junction delivers the signal to the ventricles while also slowing it, so the atria can relax before the ventricles contract. Disturbances in the heart's electrical system may lead to various rhythmic problems that can cause the heart to beat irregularly, too fast or too slow. Irregular heart beats, or arrhythmia, are caused by physiological or pathological disturbances in the discharge of electrical impulses from the sinoatrial node, in the transmission of the signal through the heart tissue, or spontaneous, unexpected electrical signals generated within the heart. One type of arrhythmia is tachycardia, which is an abnormal rapidity of heart action. There are several different forms of atrial tachycardia, including atrial fibrillation and atrial flutter. With atrial fibrillation, instead of a single beat, numerous electrical impulses are generated by depolarizing tissue at one or more locations in the atria (or possibly other locations). These unexpected electrical impulses produce irregular, often rapid heartbeats in the atrial muscles and ventricles. Patients experiencing atrial fibrillation may suffer from fatigue, activity intolerance, dizziness and even strokes. The precise cause of atrial fibrillation, and in particular the depolarizing tissue causing "extra" electrical signals, is currently unknown. As to the location of the depolarizing tissue, it is generally agreed that the undesired electrical impulses often originate in the left atrial region of the heart. Recent studies have expanded upon this general understanding, suggesting that nearly 90% of these "focal triggers" or electrical impulses are generated in one (or more) of the four pulmonary veins (PV) extending from the left atrium. In this regard, as the heart develops from an embryotic stage, left atrium tissue may grow or extend a short distance into one or more of the PVs. It has been postulated that this tissue may spontaneously depolarize, resulting in an unexpected electrical impulse(s) propagating into the left atrium and along the various electrical pathways of the heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Ablation stent for treating atrial fibrillation Inventor(s): Bowe, Wade A.; (Temecula, CA), Fellows, Chris; (Seattle, WA), Wood, David S.; (Temecula, CA) Correspondence: SCHWEGMAN, LUNDBERG, WOESSNER & KLUTH, P.A.; P.O. BOX 2938; MINNEAPOLIS; MN; 55402; US Patent Application Number: 20030018362 Date filed: April 16, 2002

Patents 163

Abstract: An apparatus and method for treating atrial fibrillation with ablation therapy in which a stent is deployed within a pulmonary vein and tissue surrounding the stent is ablated with radiofrequency energy to stop discharges from ectopic foci in the vein from reaching the left atrium. The deployed stent can then be left in place to prevent stenosis of the vein as well as allowing repeat ablation procedures as needed. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/298,738, filed on Jun. 15, 2001, under 35 U.S.C. 119(e). This invention pertains to methods for treating atrial tachyarrhythmias such as atrial fibrillation. In particular, the invention relates to an apparatus and method for treating atrial fibrillation by ablation therapy. Fibrillation refers to a condition in which muscle fibrils enter a state of extremely rapid, small-scale contractions that do not coordinate to effect contraction of the muscle as a whole. When this occurs in the left ventricle, the heart chamber responsible for pumping blood into the arterial vasculature, it is serious and rapidly fatal. When it occurs in the musculature of the atria, it is less immediately serious and not necessarily fatal. It is still important to treat atrial fibrillation, however, for several reasons. First, atrial fibrillation is associated with a loss of atrio-ventricular synchrony which can be hemodynamically compromising and cause such symptoms as dyspnea, fatigue, vertigo, and angina. Atrial fibrillation can also predispose to strokes resulting from emboli forming in the left atrium. Although drug therapy, in-hospital cardioversion, and implantable cardioverter/defibrillators are acceptable treatment modalities for atrial fibrillation, a curative approach such as ablation therapy offers a number of advantages to certain patients, including convenience and greater efficacy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Animal model of atrial fibrillation and screening and therapeutic methods relating thereto Inventor(s): Kupershmidt, Sabina; (Nashville, TN), Roden, Dan M.; (Nashville, TN) Correspondence: JENKINS & WILSON, PA; 3100 TOWER BLVD; SUITE 1400; DURHAM; NC; 27707; US Patent Application Number: 20030167015 Date filed: June 8, 2001 Abstract: An animal model of atrial fibrillation and a method of identifying an animal exhibiting an atrial fibrillation phenotype. The method includes providing an animal having a minK (-/-) genotype; recording electrocardiograms from the animal over an extended time period; and identifying an atrial fibrillation pattern in the electrocardiograms to thereby identify the animal as exhibiting an atrial fibrillation phenotype. A method of screening candidate substances for activity in the treatment of atrial fibrillation using an animal model is also disclosed, as is a method of treating atrial fibrillation using a candidate compound identified as having activity in the treatment of atrial fibrillation. Excerpt(s): This application is based on and claims priority to U.S. Provisional Application Serial No. 60/210,695, filed Jun. 9, 2000, the entire contents of which are herein incorporated by reference. The present invention pertains generally to an animal model for atrial fibrillation. More particularly, the present invention pertains to a minK (-/-) animal model exhibiting an atrial fibrillation phenotype, and to screening and therapeutic methods relating to the animal model. Atrial fibrillation is a common health problem in the United States, affecting 2-5 million individuals. Symptoms may range


from none to palpitations to exercise limitation due to uncontrolled rates and/or development of decreased cardiac contractility. In addition, atrial fibrillation is a major risk factor for stroke. The age distribution for atrial fibrillation is bell-shaped with a peak at approximately 75 years. The aging of the American population indicates that the incidence of this problem, and its attendant public health burden, is likely to rise substantially over the next decade or two, as the "baby boom" generation enters the age at which atrial fibrillation is especially common. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anthranilamides and methods of their use Inventor(s): Brendel, Joachim; (Bad Vilbel, DE), Hemmerle, Horst; (Indianapolis, IN), Kleemann, Heinz-Werner; (Bischofsheim, DE), Peukert, Stefan; (Frankfurt, DE), Pirard, Bernard; (Frankfurt, DE) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030187033 Date filed: April 26, 2002 Abstract: The present invention is related to anthranilamides of formula I, 1in which R(1) to R(7) have the meanings indicated herein, a process for their preparation, their use as medicaments, and pharmaceutical preparations containing them. The compounds act on the Kv1.5 potassium channel and inhibit a potassium current which is referred to as the ultra-rapidly activating delayed rectifier in the atrium of the human heart. The compounds are therefore suitable for use as novel antiarrhythmic agents for the treatment and prophylaxis of atrial arrhythmias (e.g., atrial fibrillation (AF) or atrial flutter). Excerpt(s): in which R(1), R(2), R(3), R(4), R(5), R(6) and R(7) have the meanings indicated hereinafter, to their preparation and use, and in particular, to their use as pharmaceuticals. The compounds of formula I have not previously been disclosed. They act on the Kv1.5 potassium channel in the atrium of the human heart, which is referred to as ultra-rapidly activating delayed rectifier, and inhibit the potassium current. The compounds are therefore suitable as novel antiarrhythmic agents for the treatment and prophylaxis of atrial arrhythmias, e.g., atrial fibrillation (AF) or atrial flutter. Atrial fibrillation (AF) and atrial flutter are the most common and persistent cardiac arrhythmias. Their occurrence increases with increasing age and frequently leads to other fatal symptoms, such as stroke. AF affects about 1 million Americans each year and leads to more than 80,000 strokes annually in the USA. The class I and III antiarrhythmic agents in use at present reduce the rate of AF occurrence, but can only be used in a limited manner due to their proarrhythmic side effects. Consequently, there is a great medical need to develop better medicaments for the treatment of atrial arrhythmias (S. Nattel (1995) "Newer developments in the management of atrial fibrillation," Am. Heart J., 130:1094-1106). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 165

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Anthranilamides with heteroarylsulfonyl side chain, process of preparation, and use Inventor(s): Bohme, Thomas; (Russelsheim, DE), Brendel, Joachim; (Bad Vilbel, DE), Kleemann, Heinz-Werner; (Bischofsheim, DE), Peukert, Stefan; (Frankfurt, DE) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030114499 Date filed: June 12, 2002 Abstract: This invention encompasses anthranilamides with heteroarylsulfonyl side chain, process for their preparation, their use as medicament or diagnostic aid, and pharmaceutical preparations containing them. Compounds of formula I, 1in which R1 to R7 have the meanings stated in the claims, act on the Kv1.5 potassium channel and inhibit a potassium current which is referred to as the ultra-rapidly activating delayed rectifier in the atrium of the human heart. They are therefore suitable as novel antiarrhythmic ingredients, such as for the treatment and prophylaxis of atrial arrhythmias, e.g. atrial fibrillation (AF) or atrial flutter. Excerpt(s): This application claims the priority of German application No. 10128331.8, filed on Jun. 12, 2001, under 35 U.S.C. 119, which is incorporated by reference. and the pharmaceutically acceptable salts thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Arrhythmia notification Inventor(s): Hess, Michael F.; (Minneapolis, MN), Mehra, Rahul; (Stillwater, MN), Sheth, Nirav Vijay; (Coon Rapids, MN), Ujhelyi, Michael R.; (Maple Grove, MN) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030050566 Date filed: September 7, 2001 Abstract: Notifying a patient or another person of an arrhythmia episode facilitates management of atrial fibrillation (AF) and other arrhythmias, including atrial flutter, atrial tachycardia, and supra ventricular tachycardia, thus enabling the patient to take corrective action even in the absence of symptoms or latent cardiac problems. For example, the patient may be prompted to take a medication, to initiate electrical therapy in the form of pacing or defibrillation, or to seek medical attention. Notification may be issued either by an implantable medical device or by an external device in communication with the implantable medical device. Various types of notifications may be issued under a variety of conditions, some of which may be associated with the duration of an episode. Excerpt(s): The invention relates to implantable medical devices. More particularly, the invention relates to implantable medical devices for treatment of cardiac arrhythmias. The heart functions by generating electrical signals to initiate physical contractions of various portions of the heart in a specific and timed sequence. These electrical signals are generated by the sinus node in the upper right atrial wall near the base of the heart and are conducted through the upper heart chambers, i.e., the right and left atria, and cause them to contract in a synchronous manner. The contractions force the blood contained in the atria into the right and left ventricles, or lower heart chambers. An


electrical depolarization wave then travels through and around the ventricles, causing the ventricles to contract and force the blood throughout the vascular system. The contraction of the right and left ventricles proceeds in an organized fashion that optimizes emptying of the ventricles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Atrial cardiac pacemaker Inventor(s): Thong, Tran; (Portland, OR) Correspondence: HAHN LOESER & PARKS, LLP; TWIN OAKS ESTATE; 1225 W. MARKET STREET; AKRON; OH; 44313; US Patent Application Number: 20030167076 Date filed: December 27, 2002 Abstract: The invention concerns a pacemaker (52) designed for emitting stimulation impulses to an atrium (20) of a heart (22), with a connection for an atrial electrode wire (14) for emitting electrical impulses to the atrium (20), with an atrial stimulation impulse generator (24) that can be connected to the electrode wire (14) and is designed to generate atrial stimulation impulses that are to be emitted over an electrode wire, with a control unit (38) that is connected to the atrial stimulation impulse generator (24) and designed to trigger the stimulation impulse generator (24) in order to generate and emit atrial stimulation impulses, wherein the control unit (38) is designed in an AFprevention mode that triggers the stimulation impulse generator (24) in order to generate a stimulation impulse sequence that is suitable for preventing atrial fibrillation (AF). It is characterized by an interval timer (34) that is connected to the control unit (32) and designed to turn the AF-prevention mode on and off according to the time of day and thereby activate or deactivate, in a time-controlled manner, the generation and emission of the stimulation impulse sequences preventing atrial fibrillation. Excerpt(s): The invention concerns a pacemaker that is designed to emit stimulation impulses to an atrium of a heart. Such a pacemaker normally contains a connection for at least one atrial electrode wire with which electrical impulses can be emitted to an atrium of a heart and discharged into the cardiac tissue (myocardium) in the atrium. The connection for the atrial electrode wire is usually connected to an atrial stimulation generator, which is designed in such a way that it can be triggered to generate atrial stimulation impulses that are to be emitted by the atrial electrode wire. For triggering the stimulation impulse generator, an (atrial) control unit is provided that is connected to the atrial stimulation generator and designed to trigger the stimulation generator, in order to generate and emit atrial stimulation impulses. In the case interesting here, the control unit has an AF-prevention mode in which the atrial control unit triggers the stimulation generator, in order to create a stimulation sequence that is suitable for preventing atrial fibrillation. The previously sketched pacemaker is preferably an ICD (implantable cardioverter/defibrillator) with overdrive stimulation for the preventative treatment of atrial fibrillation. Customarily, such an ICD also has a connection for a ventricular electrode wire and a stimulation impulse generator for ventricular stimulation impulses that are effective in the ventricle of a heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 167

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Atrial fibrillation detection method and apparatus Inventor(s): Bock, Elizabeth Anne; (Elm Grove, WI) Correspondence: MICHAEL BEST & FRIEDRICH, LLP; 100 E WISCONSIN AVENUE; MILWAUKEE; WI; 53202; US Patent Application Number: 20030144597 Date filed: October 18, 2002 Abstract: A method and apparatus to detect irregular heart activity and estimate heart rate. In one embodiment, the heart rate estimation apparatus includes a group of six RR storage structures that receives an input of six successive RR interval values. The apparatus also includes a probability engine coupled to the group of RR storage structures, the probability engine is operable to calculate and output a mean value of the six RR interval values and a median value of the mean value and the six RR interval. In one embodiment, the apparatus carries out a method including the acts of determining a plurality of interval values between successive R waves; determining a mean of a group of six interval values; determining a median interval value for a group including the group of six interval values and the mean of the group of six interval values; and determining a running average of interval values between successive R waves using the median interval value. Excerpt(s): The present application is a continuation of U.S. patent application Ser. No. 09/750,846 filed Dec. 28, 2000, and is hereby incorporated by reference herein. The present invention relates to methods and devices used to detect irregularities in the beating of an animal heart, generally known as "arrhythmias." More particularly, the invention relates to a method and an apparatus to detect atrial fibrillation ("AF"). A variety of methods and devices have been developed to assist physicians in interpreting ECGs. One such tool is known as EKpro detection software, which is available from GE Medical Systems Information Technologies, Inc., the assignee of the present application. EKpro software is designed for monitoring ECG signals in adults and paced patients. EKpro software has particular application in detecting atrial fibrillation. AF is identified by an irregular heart rhythm and is clinically defined as uncoordinated contractions of the atria. The ECG of a patient suffering from atrial fibrillation typically demonstrates irregular ventricular contractions and the absence of P waves. If allowed to continue, AF can cause decreases in exercise tolerance and left ventricular function. In more severe cases, AF can lead to a fatal medical condition. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Bayesian discriminator for rapidly detecting arrhythmias Inventor(s): Chan, Francis Hy; (Pokfulam, HK), Fung, Peter Chin Wan; (Pokfulam, HK), Lau, Chu-pak; (Midlevel, HK), Tse, Hung-Fat; (Midlevel, HK), Xu, Weichao; (Shenzhen, CN) Correspondence: PENNIE AND EDMONDS; 1155 AVENUE OF THE AMERICAS; NEW YORK; NY; 100362711 Patent Application Number: 20030216654 Date filed: May 7, 2002 Abstract: A method for accurate and rapid automated detection of atrial fibrillation (AF), sinus rhythm (SF), and atrial flutter (AFL) is disclosed, which allows


distinguishing of these cardiac signals with lowered risk of errors by implanted pacemakers and like devices. The method includes training episodes of intra-cardiac signals (called the closed data set CDS) to evaluate five feature parameters with a discriminator classifying the signal into AF, AFL or sinus rhythm (SR). Comparison with the independent decisions of experienced physicians for each episode reveals specificity, accuracy and sensitivity of greater than 97%. Each episode is a window of intracardiac signal of interval 1-2 seconds with the discriminator providing results in less than 0.25 s. In another aspect, the method is resistant to the presence of noise in the data. In yet another aspect, more feature parameters may be used in alternative implementations including for detecting signals other than AF, AFL & SR. Excerpt(s): The invention is directed to the generation and analysis of data with a multiple-index Bayesian discriminator. More specifically, the invention is directed to methods, systems, and devices for detecting and treating arrhythmias and heart diseases. Arrhythmias are caused by a disruption of the normal electrical conduction system of the heart, causing abnormal heart rhythms. Normally, the four chambers of the heart (2 atria and 2 ventricles) contract in a very specific, coordinated manner. The signal to contract is an electrical impulse that begins in the "sinoatrial node" (the SA node), which is the body's natural pacemaker. The signal then travels through the two atria and stimulates them to contract. The signal passes through the "atrioventricular note" node (the AV node), and finally travels through the ventricles and stimulates them to contract. Problems can occur anywhere along the electrical conduction system, causing various arrhythmias. There can be a problem in the heart muscle itself, causing it to respond differently to the signal, or causing the ventricles to contract out of step with the normal conduction system. Other causes of arrhythmias include abnormal rhythmicity of the body's natural pacemaker, a shift of the pacemaker from SA node to other parts, blocks at different transmission points, abnormal pathways of impulse conduction, and spontaneous general of abnormal impulses due to ischemia (low flow to coronary arteries), hypoxia (low oxygen), ANS imbalance, lactic acidosis, electrolyte abnormality, drug toxicity, and hemodynamic abnormalities. Atrial fibrillation (AF) is the most common form of supraventricular arrhythmia and is associated with a considerable risk of morbidity and mortality. (Benjamin E J, et al., 1998 Circulation 98:946-952; Ryder K M, et al., 1999 Am J Cardiol. 84:1311R-138R; Chugh S S, et al. 2001 J Am Coll Cardiol. 37:371-377). As many as 2 million Americans are living with atrial fibrillation according to the American Heart Association. Theoretical analyses and high-density mapping studies have suggested that the most common mechanism of AF is the presence of multiple wave fronts or "wavelets" circulating irregularly throughout the atrial tissue. (Moe G K, et al., 1964 Am Heart J. 67:2961-2967; Allessie M A, et al., "Experimental Evaluation of Moe s Multiple Wavelet Hypothesis of Atrial Fibrillation" in Zipes E P, Jalife J, eds. Cardiac Electrophysiology and Arrhyhtmias. Orlando, Fla: Grune & Stratton, Inc., 1985; pp 265-275; Konings KTS, et al., 1994 Circulation 89:16651680). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 169

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Biopolar ablation electrodes and method of use Inventor(s): Pendekanti, Rajesh; (Bridgewater, NJ), Wellman, Parris S.; (Hillsborough, NJ) Correspondence: NUTTER MCCLENNEN & FISH LLP; WORLD TRADE CENTER WEST; 155 SEAPORT BOULEVARD; BOSTON; MA; 02210-2604; US Patent Application Number: 20030065327 Date filed: December 20, 2001 Abstract: Ablation instruments and methods for ablating tissue, and more particularly for treating atrial fibrillation utilizing RF energy are provided. The ablation instrument generally includes two components: a first member adapted to be placed on or adjacent to a first tissue surface, and a second member opposed to the first member and adapted to be placed on or adjacent to a second, opposed tissue surface. Each member includes a conductive element disposed on a portion thereof that is effective to communicate with a source of ablative energy. First and second conductor elements can be provided for transmitting ablative energy from an energy source to the first and second conductive elements. In use, ablative radiation is transmitted between the first and second members through the intervening tissue to form a lesion in the tissue. Excerpt(s): The present invention relates to instruments and methods for ablating tissue, and more particularly to surgical instruments and methods for ablating cardiac tissue using radiofrequency energy. Cardiac arrhythmias, such as atrial fibrillation, are a commonly occurring disorder characterized by erratic beating of the heart. The regular pumping function of the atria is replaced by a disorganized, ineffective quivering caused by chaotic conduction of electrical signals through the upper chambers of the heart. While medication can be an effective treatment for some cases, many patients are not responsive to medical therapies and require alternative treatment. As an alternative to medication, a surgical technique, known as the Maze technique, requires open chest surgery to strategically incise the atrial wall, and subsequently repair the incisions by suturing. The result of this surgery is to create scar tissue located along the incision lines and extending through the atrial wall to block electrical conductivity from one segment to another. While the Maze procedure has proven effective in restoring normal sinus rhythm, it requires considerable prolongation of cardiopulmonary bypass and aortic crossclamp time, especially when performed in combination with other open heart procedures. Over the last decade, more simplified techniques have been proposed which replace surgical incisions with ablations, or scars, formed in the heart tissue. The various energy sources used in ablation technologies include cryogenic, radiofrequency (RF), laser, and microwave energy. The ablation devices are used to create tissue lesions in an affected portion of the heart in order to block electrical conduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html


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Device and method for forming a lesion Inventor(s): Anderson, Scott C.; (Sunnyvale, CA), Gallup, David A.; (Alameda, CA), Pless, Benjamin; (Atherton, CA), Richman, Roxanne L.; (Los Gatos, CA), Ulstad, Jack E. JR.; (Boulder Creek, CA), Vaska, Matthias; (Menlo Park, CA) Correspondence: HOEKENDIJK & LYNCH, LLP; P.O. BOX 4787; BURLINGAME; CA; 94011-4787; US Patent Application Number: 20030028187 Date filed: June 12, 2002 Abstract: The invention provides apparatus and methods for mapping conduction pathways and creating lesions in the heart wall for the treatment of atrial fibrillation. The apparatus may include at least one epicardial ablation probe having a plurality of electrodes for creating a lesion. The apparatus and method facilitate the formation of a lesion which electrically isolates the pulmonary veins from the surrounding myocardium. Excerpt(s): This application is a continuation of co-pending application Ser. No. 09/356,476, filed Jul. 19, 1999, which is a continuation-in-part of application Ser. No. 09/157,824, filed Sep. 21, 1998, which is a continuation-in-part of application Ser. No. 08/943,683, filed Oct. 15, 1997, which is a continuation-in-part of application Ser. No. 08/735,036, filed Oct. 22, 1996, now abandoned, the complete disclosures of which are hereby incorporated herein by reference for all purposes. This invention relates generally to the diagnosis and treatment of electrophysiological diseases of the heart, and more specifically to devices and methods for epicardial mapping and ablation for the treatment of atrial fibrillation. Atrial fibrillation results from disorganized electrical activity in the heart muscle, or myocardium. The surgical maze procedure has been developed for treating atrial fibrillation and involves the creation of a series of surgical incisions through the atrial myocardium in a preselected pattern so as to create conductive corridors of viable tissue bounded by scar tissue. While very effective in treating atrial fibrillation, the maze procedure is highly invasive, high in moribidity and mortality, and difficult to perform by even the most skilled surgeons. The procedure not only requires a median stemotomy or other form of gross thoracotomy for access to the heart, but requires stopping the heart and establishing cardiopulmonary bypass, to which a significant part of the trauma, morbidity and mortality of the maze procedure may be attributed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Device and method for needle-less interstitial injection of fluid for ablation of cardiac tissue Inventor(s): Jahns, Scott E.; (Husdon, WI) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030216724 Date filed: February 3, 2003 Abstract: Methods and apparatus for delivering precise amounts of fluid under pressure into cardiac tissue for the purpose of facilitating ablation of the tissue along a desired lesion line. One method injects fluid under pressure through a discharge orifice in a

Patents 171

needle-less injection device. The injected fluid can be a cytotoxic fluid and/or a highly conductive fluid injected in conjunction with radio frequency ablation to create an ablative virtual electrode. The injected fluid can provide deeper and narrower conduction paths and resulting lesions. Radio frequency ablation can be performed at the same time as the fluid injection, using the injection device as an electrode, or subsequent to the fluid injection, using a separate device. In some methods, the injected fluid is a protective fluid, injected to protect tissue adjacent to the desired lesion line. Fluid delivery can be endocardial, epicardial, and epicardial on a beating heart. The present methods find one use in performing maze procedures to treat atrial fibrillation. Excerpt(s): The present application claims priority to U.S. provisional patent application serial No. 60/381,217, filed on May 16, 2002, titled DEVICE AND METHOD FOR ABLATION OF CARDIAC TISSUE, herein incorporated by reference in its entirety. The present application is related to commonly assigned U.S. patent application Ser. No. __/___,___, filed on ______, titled DEVICE AND METHOD FOR ABLATION OF CARDIAC TISSUE, [disclosure number P-9925]. The present invention relates generally to the field of devices for cardiac surgery, and more specifically to devices for ablation of cardiac tissue. The present invention is directed toward treatment of tachyarrhythmias, which are heart rhythms in which one or more chambers of the heart exhibit an excessively fast rhythm. In particular, the present invention is directed toward treatment of tachycardias, which are due to the presence of ectopic foci within the cardiac tissue or due to the presence of aberrant condition pathways within the cardiac tissue. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Electrophysiologic measure of endpoints for ablation lesions created in fibrillating substrates Inventor(s): Benser, Michael E.; (Birmingham, AL), Hall, Jeffrey A.; (Birmingham, AL), Ideker, Raymond E.; (Birmingham, AL), Sanchez, Javier E.; (Homewood, AL), Smith, William M.; (Birmingham, AL) Correspondence: MYERS BIGEL SIBLEY & SAJOVEC; PO BOX 37428; RALEIGH; NC; 27627; US Patent Application Number: 20030028183 Date filed: March 27, 2001 Abstract: Methods, systems, and computer program products measure electrical activity of the cardiac tissue proximate the lesion site during an ablation treatment, and then compare the measurements to determine whether the lesion is clinically efficacious so as to be able to block myocardial propagation. The methods can include obtaining the measurements and performing the ablation therapy while the subject is experiencing atrial fibrillation and may measure the standard deviation of the electrogram signal.Certain of the methods and systems measure the electrical activity at multiple sites about the lesion site to detect whether the lesion is uniformly or sufficiently transmural about its length (and through the thickness of the wall). Excerpt(s): The present invention is related to cardiac ablation treatments. Ablation therapies can be used to treat certain conditions of the heart including atrial fibrillation. Ablation therapies are typically administered to regions in the heart to kill tissue and form lesions in selected heart tissue such that the lesion formed by the ablated heart tissue is unable to support conduction, and hence, fibrillation. Generally stated, during atrial fibrillation, propagation of the electrical excitation wavefront travels along the


surface substrate tissue (wall). To be effective, the ablated tissue lesion should be transmural such that the tissue is destroyed along the surface and through the thickness of the substrate tissue (or the thickness of the wall) about the lesion (i.e., not merely a surface or superficial lesion). Typically, the ablation therapy is delivered so that a desired contiguous (conventionally linear) lesion pattern or length is formed in the selected myocardial tissue, which kills all viable excitable cells about the surface of the lesion and through the wall thickness underlying the lesion so that the heart is unable to maintain fibrillation. That is, the lesion electrically insulates and separates side-by-side adjacent segments in the atria so that the adjacent segments are effectively electrically isolated from each other by the lesion in a manner that inhibits electrical conduction between the adjacent segments. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Implantable cardiac stimulation device that defibrillates the atria while avoiding the ventricular vulnerable period and method Inventor(s): Bornzin, Gene A.; (Simi Valley, CA), Levine, Paul A.; (Santa Clarita, CA) Correspondence: PACESETTER, INC.; 15900 Valley View Court; Sylmar; CA; 913929221; US Patent Application Number: 20030163165 Date filed: February 28, 2002 Abstract: An implantable cardiac stimulation device applies defibrillating electrical energy to the atria of a heart at a time which avoids inducing ventricular fibrillation of the heart. The device includes an atrial fibrillation detector that detects atrial fibrillation of the heart, a pacing pulse generator that applies a ventricular pacing pulse to the heart responsive to detection of atrial fibrillation, a timer that times a time period through an evoked response and a T-wave caused by the pacing pulse, and a defibrillation pulse generator that applies defibrillating electrical energy to the atria of the heart after the timer completes the timing of the time period. Excerpt(s): The present invention generally relates to an implantable cardiac stimulation device. The invention more particularly relates to such device and method for defibrillating the atria of a heart while avoiding the ventricular vulnerable period of the heart. Atrial fibrillation is a common cardiac arrhythmia. Although it is not life threatening, it is associated with strokes thought to be caused by blood clots forming in areas of stagnant blood flow as a result of prolonged atrial fibrillation. Symptoms of atrial fibrillation may include heart palpitations, dizziness, and even loss of consciousness. Atrial fibrillation can occur suddenly. It is caused by chaotic activity of the atria of the heart. The chaotic atrial activity in turn causes the ventricular activity to be disassociated from the atrial activity. The ventricular activity becomes rapid and variable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 173

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METHOD AND APPARATUS TACHYARRHYTHMIAS

FOR

TREATING

SUPRAVENTRICULAR

Inventor(s): HSU, WILLIAM; (CIRCLE PINES, MN), KENKNIGHT, BRUCE H.; (MAPLE GROVE, MN) Correspondence: SCHWEGMAN LUNDBERG WOESSNER & KLUTH; P O BOX 2938; MINNEAPOLIS; MN; 55402 Patent Application Number: 20030023271 Date filed: March 19, 1998 Abstract: A system and method for treating atrial fibrillation using atrial pacing pulses to convert an atrial fibrillation to non-fibrillation atrial arrhythmia prior to delivering a low energy cardioversion/defibrillation shock. The system and method treats atrial fibrillations by first applying a plurality of pacing pulses to the atria which converts the atrial fibrillation to non-fibrillation atrial arrhythmia. Ventricular intervals are concurrently sensed and analyzed while the plurality of electrical pacing pulses are being applied. Upon detecting a period of stable ventricular intervals, the system then proceeds to deliver a low-energy cardioverting/defibrillating pulse of electrical energy across the atria of the heart. Excerpt(s): The present invention relates generally to implantable medical devices and in particular to implantable electrical pulse generators for treating supraventricular tachyarrhythmias. Effective, efficient ventricular pumping action depends on proper cardiac function. Proper cardiac function, in turn, relies on the synchronized contractions of the myocardium at regular intervals. When the normal cardiac rhythm is initiated at the sinoatrial node, the heart is said to be in sinus rhythm. However, when the heart experiences irregularities in the coordinated contraction of the myocardiurn, due to electrophysiologic disturbances caused by a disease process or from an electrical disturbance, the heart is denoted to be arrhythmic. The resulting cardiac arrhythmia impairs cardiac efficiency and can be a potential life threatening event. In the supraventricular region of the heart, electrophysiologic disturbances are called supraventricular tachyarrhythmias (SVT). SVT can take several distinguishable forms, including paroxysmal atrial tachycardia, atrial flutter, or atrial fibrillation. SVT are selfsustaining process and may be paroxysmal or chronic. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and arrangement for using atrial pacing to prevent early recurrence of atrial fibrillation Inventor(s): Casavant, David A.; (Reading, MA), Euler, David E.; (Minnetonka, MN), Sheth, Nirav V.; (Coon Rapids, MN), Ujhelyi, Michael R.; (Maple Grove, MN) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030144698 Date filed: January 31, 2002 Abstract: A method for preventing early recurrence of atrial fibrillation by pacing a heart in AAI mode at a rate faster than the intrinsic rate for a selected period of time immediately after delivering therapy to terminate the fibrillation. Ventricular backup pacing in VVI mode may also be provided during the atrial pacing.


Excerpt(s): This invention relates to the field of pacemakers and pacing algorithms; and, in particular, to delivering atrial overdrive pacing to an atrium to decrease the recurrence of atrial fibrillation after the delivery of a therapy to terminate an atrial arrhythmia. Atrial fibrillation is probably the most common form of cardiac arrhythmia. Patients afflicted with atrial fibrillation generally experience rapid and irregular heartbeats and may even experience dizziness as a result of reduced cardiac output. Atrial fibrillation occurs suddenly and can be corrected by an electrical shock into the atria of the heart. Implantable atrial defibrillators detect the presence of atrial fibrillation and provide a single cardioverting pulse of electrical energy (or electrical shock) as the therapy. However, atrial fibrillation usually returns within minutes after delivery of the electrical therapy in about one-half of the patients with atrial fibrillation episodes. One mechanism for preventing atrial fibrillation involves providing atrial overdrive pacing therapy. This type of therapy paces the right atrium at a rate faster than the atrial intrinsic rate for a predetermined period of time. The implanted device applies pacing pulses to the right atrium (referred to as "A pulses") at a time in the cardiac cycle that is just prior to the occurrence of a spontaneous atrial depolarization (referred to as a "P-wave"). Thus, in overdrive pacing, a sequence of A-pulses applied to the atrium causes the atrium to depolarize at a time in the cardiac cycle that is slightly before the spontaneous occurrence of the P-wave, thereby preventing the onset of an atrial fibrillation episode. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and device for performing cooling or cryo-therapies, for, e.g., angioplasty with reduced restenosis or pulmonary vein cell necrosis to inhibit atrial fibrillation employing tissue protection Inventor(s): Cooper, Stephen R.; (Carlsbad, CA), Dobak III, John D.; (La Jolla, CA), Inderbitzen, Rebecca S.; (San Diego, CA), Kramer, Hans W.; (Temecula, CA), Yon, Steven A.; (San Diego, CA) Correspondence: Mark D Wieczorek; Innercool Therapies Inc; 3931 Sorrento Valley Boulevard; San Diego; CA; 92121; US Patent Application Number: 20030125721 Date filed: October 29, 2002 Abstract: An enhanced method and device are provided to treat atrial fibrillation or inhibit or reduce restenosis following angioplasty or stent placement. A balloon-tipped catheter is disposed in the area treated or opened through balloon angioplasty immediately following angioplasty. The balloon, which can have a dual balloon structure, may be delivered through a guiding catheter and over a guidewire already in place. A fluid such as a perfluorocarbon flows into the balloon to freeze the tissue adjacent the balloon, this cooling being associated with reduction of restenosis. A similar catheter may be used to reduce atrial fibrillation by inserting and inflating the balloon such that an exterior surface of the balloon contacts at least a partial circumference of the portion of the pulmonary vein adjacent the left atrium. In another embodiment, blood perfusion is performed simultaneously. In another embodiment, tissue contacted by the cryoablation catheter, undesired to be ablated, is protected against damage by a separate heating step. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/787,599 filed Mar. 21, 2001, entitled "Method and Device for Performing Cooling- or Cryo-Therapies for, e.g., Angioplasty with Reduced Restenosis or Pulmonary Vein Cell

Patents 175

Necrosis to Inhibit Atrial Fibrillation" which is a continuation-in-part of U.S. patent application Ser. No. 09/516,319, filed Mar. 1, 2000, entitled "Method and Device for Performing Cooling-or Cryo-Therapies for, e.g., Angioplasty with Reduced Restenosis or Pulmonary Vein Cell Necrosis to Inhibit Atrial Fibrillation" which is a continuationin-part of U.S. patent application Ser. No. 09/052,545, filed Mar. 31, 1998, entitled "Circulating Fluid Hypothermia Method and Apparatus" and U.S. patent application Ser. No. 09/215,038, filed Dec. 16, 1998, entitled "Inflatable Catheter for Selective Organ Heating and Cooling and Method of Using the Same". This application is also continuation-in-part and utility conversion of Provisional Application Serial Nos.: 60/272,550 filed Mar. 1, 2001, entitled "Method and Apparatus for Inhibiting Tissue Damage During Cryo-Ablation", and 60/273,095 filed Mar. 2, 2001, entitled "Annular Ring Balloon for Pulmonary Vein Cryoplasty", all of the above are incorporated herein. Balloon angioplasty, or the technology of reshaping of a blood vessel for the purpose of establishing vessel patency using a balloon tipped catheter, has been known since the late 1970's. The procedure involves the use of a balloon catheter that is guided by means of a guidewire through a guiding catheter to the target lesion or vessel blockage. The balloon typically is equipped with one or more marker bands that allow the interventionalist to visualize the position of the balloon in reference to the lesion with the aid of fluoroscopy. Once in place, i.e., centered with the lesion, the balloon is inflated with a biocompatible fluid, and pressurized to the appropriate pressure to allow the vessel to open. Typical procedures are completed with balloon inflation pressures between 8 and 12 atmospheres. A percentage of lesions, typically heavily calcified lesions, require much higher balloon inflation pressures, e.g., upward of 20 atmospheres. At times, the balloon inflation procedure is repeated several times before the lesion or blockage will yield. The placement of stents after angioplasty has become popular as it reduces the rate of restenosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and device to prevent cardiac dysrhythmias Inventor(s): Unsworth, John D.; (Flamborough, CA) Correspondence: John D. Unsworth; c/o Vasotech Corp.; Suite 107; 7 Innovation Dr.; Flamborough; ON; L9H7H-9; CA Patent Application Number: 20030187382 Date filed: February 18, 2003 Abstract: A device to treat dysrhythmias of the heart, for example atrial fibrillation, by creating artificial conduction pathways, fields or patterns. These artificial pathways or fields are created by injecting materials having desired electrical properties into the walls of the heart. Excerpt(s): This application is a continuation-in-part application of U.S. Pat. No. 6,520,927, granted Feb. 18, 2003, having been filed Jan. 14, 2000. This invention generally relates to the conduction system of the heart and the creation of artificial lines of conduction in the wall of the heart to reduce or eliminate cardiac dysrhythmias, for example atrial fibrillation and also to conduct normal impulses from the senatorial node to avoid the necessity of implanting an artificial pacemaker. The conduction system of the normal heart involves impulse formation at the sinus node and impulse propagation through the rest of the heart. Automaticity, or the property of generating spontaneous depolarization to threshold, enables the SA and AV nodes to generate


cardiac action potentials without any stimulus. Automaticity is also present in the left atrium and is thought to contribute to the cause of atrial fibrillation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and system for terminating atrial fibrillation by inducing a ventricular extrasystole with combipolar pacing Inventor(s): Kupper, Bernhard C.H.; (Dusseldorf, DE) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030032986 Date filed: April 30, 2001 Abstract: A method and system for pacing cardiac tissue is provided. Atrial fibrillation is detected in the cardiac tissue. An area of the cardiac tissue is paced with at least one atrial electrode and simultaneously paced with at least one ventricular electrode. A ventricular extra-systole is induced, thereby terminating the atrial fibrillation. Excerpt(s): The present invention relates to the field of implantable medical devices. More particularly, the present invention relates to cardiac pacing systems that provide a method for using pacing pulses to terminate an atrial fibrillation by inducing a ventricular extra-systole through combipolar pacing. Tachyarrhythmias are episodes of high-rate cardiac depolarizations. Tachyarrhythmias may occur in one chamber of the heart or may be propagated from one chamber to another. Some tachyarrhythmias are sufficiently high in rate to compromise cardiac output from the chamber(s) affected, leading to loss consciousness or death, in the case of ventricular fibrillation or weakness and dizziness in the case of atrial fibrillation. Atrial fibrillation is often debilitating, due to the loss of atrial cardiac output, and may sometimes lead to ventricular fibrillation. Generally, fibrillation may be terminated by administering high energy level cardioversion/defibrillation shocks or pulses until the fibrillation is terminated. For example, in the context of implantable anti-arrhythmia devices, these pulses may be applied by means of large surface area electrodes on or in the chamber to be defibrillated. However, the high energy level pulses are often sufficient to cause pain to the patient. Thus, it would be desirable to prevent or decrease the occurrence of atrial fibrillation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for identification and visualization of atrial tissue and therapeutical use thereof Inventor(s): Dubuc, Marc; (Longueuil, CA), Guerra, Peter; (St-Leonard, CA), Tardif, Jean-Claude; (Laval, CA) Correspondence: OGILVY RENAULT; 1981 MCGILL COLLEGE AVENUE; SUITE 1600; MONTREAL; QC; H3A2Y3; CA Patent Application Number: 20030120142 Date filed: September 25, 2002 Abstract: The present invention relates to a method for visual identification of atrial tissue comprising the steps of visualizing a site of atrial tissue formation using a device

Patents 177

adapted for visualizing and obtaining an image; and analyzing the image to determine the presence, location and/or distribution of atrial tissue in the site. The present invention also relates to a method for the treatment of atrial fibrillation in a patient, comprising the steps of identifying atrial tissue in a site of atrial tissue formation by introducing a device adapted for visualization into the site; and substantially ablating atrial tissue previously identified. The present invention further relates to a method for determining the shape of an atrial tissue formation comprising the step of identifying atrial tissue site potential indicative of the shape of the atrial tissue. Excerpt(s): This invention relates to a method for the identification of atrial tissue and method of treatment of atrial fibrillation using same. The treatment of atrial fibrillation (AF) has evolved substantially in recent years, with increasing emphasis being placed on catheter-based approaches to therapy. Hassaguerre and colleagues demonstrated that AF is actually initiated by atrial ectopics originating in the pulmonary veins (Haissaguerre M, et al., N Engl J Med. 1998;339:659-66) and that ablation of these foci could result in a cure of AF. The pulmonary veins (PV) were found to have unique electrophysiological properties, and recording studies suggest that certain PVs have longer sleeves of myocardial tissue thought to be responsible for the generation of these ectopic foci (Chen S A, et al., Circulation. 1999;100:1879-86). Anatomic evidence of sleeves of atrial tissue extending several centimeters into the PVs was described as early as 1966 by Nathan (Nathan H, Eliakim M., Circulation. 1966;34:412-22). More recent studies by Saito et al confirmed the presence of myocardial sleeves in the PV, with the longest sleeves being visualized in the superior veins (Saito T, et al., J Cardiovasc Electrophysiol. 2000;11:888-94). Ablation of ectopic foci originating in the PVs was initially hampered by the lack of an adequate endpoint for the procedure, resulting in recurrences of AF. For this reason, elimination of PV potentials and PV electrical isolation was shown to be a more satisfactory endpoint (Haissaguerre M, et al., Circulation. 2000;101:1409-1417). Further, attempts at eliminating these potentials demonstrated that the conducting tissue and its breakthrough points were often asymmetrically distributed along the vein ostium (Hocini M, et al., Pacing Clin Electrophysiol. 2000;23:1828-31; Haissaguerre M, et al., Circulation. 2000;102:2463-5). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of and apparatus for detecting arrhythmia and fibrillation Inventor(s): Wiesel, Joseph; (West Hempstead, NY) Correspondence: GIBBONS, DEL DEO, DOLAN, GRIFFINGER & VECCHIONE; 1 RIVERFRONT PLAZA; NEWARK; NJ; 07102-5497; US Patent Application Number: 20030055351 Date filed: October 30, 2002 Abstract: The presence of irregular heartbeat and/or possible atrial fibrillation is determined by analyzing a measured pulse rate pattern or heart rate pattern. The standard deviation and mean of time intervals each corresponding to a respective heartbeat are determined and compared to a threshold value. When quotient formed by dividing the standard deviation by the mean has a value greater than or equal to the threshold value, the shortest one of the time intervals and its succeeding time intervals are determined, and the succeeding time interval is compared to the mean. If the succeeding time interval is less than the mean, then the heartbeat is irregular. Alternatively, if the succeeding time interval is greater than the mean, the shortest time interval and its succeeding time interval are eliminated from the sample values, a new


mean and standard deviation are determined, and the quotient of the new standard deviation divided by the new mean are compared to the threshold value. When the quotient is greater than the threshold value, the next shortest interval is determined, and the absolute value of the difference between the next shortest interval and the shortest interval is compared to an empirically determined value. If the difference is greater than the empirically determined value, the heartbeat is irregular. Alternatively, if the difference is greater than the empirically determined value, then the next shortest interval and its succeeding interval are redefined as the new shortest interval and is succeeding interval. The steps are repeated until it is determined that the heartbeat is regular or irregular. Excerpt(s): The present invention generally relates to a method of and an apparatus for detecting irregular heartbeats and, more particularly, to monitoring and analyzing pulse rates for detecting possible atrial fibrillation. The heart is the major muscle that functions as the primary pump for blood flow throughout the body. The heart contains two upper chambers called atria and two lower chambers called ventricles. The right atrium receives oxygen-depleted blood while the left atrium receives blood enriched with oxygen from the lungs. When the atria are full, the outlet valves within the heart open and the atria squeeze blood into the ventricles. The right ventricle then pumps oxygen-depleted blood to the lungs while the left ventricle pumps oxygen-enriched blood to all parts of the body. In this fashion, the heart functions primarily as a double sided pump. The heart's internal pacemaker, known as the sinus node, signals the start of each heart beat. This signal originates in the right atrium in the sinoatrial node and travels simultaneously to the left atrium and down to the interatrial septum to the atrioventricular node. The cycle of electrical stimulation that normally occurs is referred to as normal sinus rhythm. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods & devices for minimally invasive cardiac surgery for atrial fibrillation Inventor(s): Bertolero, Arthur A.; (Danville, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030158464 Date filed: December 4, 2002 Abstract: Devices for enhancing minimally invasive cardiac surgery include a visualization device including an inflatable balloon at or near the distal end. Some visualization devices also include one or more lumens for allowing the introduction of one or more devices to a surgical site through the visualization device. Systems of the invention involve a visualization device which has at least one lumen for allowing introduction of an ablation device and/or other devices. A visualization device with an inflatable balloon may be positioned to create a space between a heart and pericardium when the balloon is inflated. Excerpt(s): The present application claims priority to U.S. Provisional Patent Application Serial No. 60/337,070, filed Dec. 4, 2001, entitled "Methods and Devices for the Least Invasive Cardiac Surgery of Atrial Fibrillation," the entire contents of which is hereby incorporated by reference. The present invention relates generally to medical devices and methods. More specifically, the invention relates to devices and methods for enhancing minimally invasive cardiac surgery of atrial fibrillation. Atrial fibrillation

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(AF) is a heart beat rhythm disorder (or "cardiac arrhythmia") in which the upper chambers of the heart known as the atria quiver rapidly instead of beating in a steady rhythm. This rapid quivering reduces the heart's ability to properly function as a pump. AF is characterized by circular waves of electrical impulses that travel across the atria in a continuous cycle. It is the most common clinical heart arrhythmia, affecting more than two million people in the United States and some six million people worldwide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and apparatus employing ionizing radiation for treatment of cardiac arrhythmia Inventor(s): Bonan, Raoul; (Mirabel, CA), Griffis, Jack C. III; (Decatur, GA), Larsen, Charles E.; (Cumming, GA), Lerohl, Andrew L.; (Hoschton, GA), Schumer, Douglas B.; (Atlanta, GA), Trip, Roelof; (Lawrenceville, GA) Correspondence: COOK, ALEX, MCFARRON, MANZO, CUMMINGS & MEHLER LTD; SUITE 2850; 200 WEST ADAMS STREET; CHICAGO; IL; 60606; US Patent Application Number: 20030153802 Date filed: September 23, 2002 Abstract: Method and apparatus are disclosed employing ionizing radiation for forming lines of ablation or lesions in cardiac tissue to treat atrial fibrillation or other electrophysiological problems with the heart. The apparatus may include a catheter in which the radiation source is advanced hydraulically after the catheter is in place within the heart. Various fixation devices are also disclosed for fixing the location of the catheter within the heart. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/324,299, filed Sep. 24, 2001, and incorporates by reference aforesaid application. The present invention generally relates to the treatment of cardiac arrhythmias (atrial and ventricular) such as, but not limited to, atrial fibrillation and/or to the treatment of vascular restenosis after the use of other ablation techniques. More specifically, the present invention is directed to unique apparatus and/or methods employing ionizing radiation for ablating cardiac issue to treat cardiac arrhythmias. The coordinated contraction of the various chambers of the human heart during a normal heartbeat is controlled by a relatively complex electrical system. The electrical signal that initiates each heartbeat begins at an area in the right atrium commonly called the "sinus node" or the "sinoatrial node." The electrical signal rapidly spreads across the right and left atria. The electrical signal is conducted to the ventricles of the heart through a connection called the atrioventricular node (AV node). From the atrioventricular node, the electrical signal passes along a bundle of special cells in the heart, known as a Bundle of His, which spreads the electrical signal rapidly through the ventricles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html


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Methods and apparatus for reducing the likelihood of atrial fibrillation Inventor(s): Warman, Eduardo N.; (Maple Grove, MN), Markowitz, H. Toby; (Roseville, MN) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030083706 Date filed: October 30, 2001 Abstract: Methods and apparatus for reducing the incidence of atrial fibrillation includes selecting a desired ventricular rate, pacing the ventricle of the heart at the desired ventricular rate, and pacing the atrium of the heart at twice the desired ventricular rate while the desired ventricular rate is less than a preferred rate. Some methods of the present invention include pacing the atrium of the heart at the desired ventricular rate while the desired ventricular rate is greater than the preferred rate. Other methods of the present invention include pacing the atrium of the heart at a predetermined/preferred atrial rate while the desired ventricular rate is greater than the preferred rate. Excerpt(s): The present invention relates generally to cardiac pacemakers. More particularly, the present invention relates to cardiac pacemakers for treating atrial fibrillation. An arrhythmia is a heart rhythm disorder which interferes with the life sustaining blood circulation activities of the heart. Examples of arrhythmias include ventricular fibrillation and atrial fibrillation. Ventricular fibrillation effects the lower chambers of the heart (the ventricles) and atrial fibrillation effects the upper chambers of the heart (the atria). Ventricular fibrillation is a rapid and disorganized firing of muscle fibers within the ventricular myocardium. During ventricular fibrillation, the ventricles do not contract in an organized manner, no blood is pumped, and blood pressure falls to zero. Patient death may occur within 4 minutes from the onset of ventricular fibrillation. Companies such as Medtronic, Inc., have developed implantable defibrillators which may be used to successfully treat ventricular fibrillation by delivering a defibrillating shock to the heart when fibrillation is detected. Atrial fibrillation occurs more frequently than ventricular fibrillation. It has been estimated that atrial fibrillation affects more than million people worldwide. As people age, their chances of developing atrial fibrillation increase dramatically. In fact, approximately 70% of all people with atrial fibrillation are over 65 years of age. Although atrial fibrillation occurs with great frequency, successful therapies for atrial fibrillation have been difficult to identify. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and compositions for use of (S)-bisoprolol Inventor(s): Devane, John; (Athlone, IE), Kelly, John; (Drumcondra, IE) Correspondence: FINNEGAN, HENDERSON, FARABOW; GARRETT & DUNNER, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030091633 Date filed: August 22, 2002 Abstract: Methods of treating, preventing, and/or managing cardiovascular conditions such as hypertension, ischemic heart disease, atrial fibrillation, congestive heart failure,

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angina pectoris, and cardiac arrhythmias, with the (S) stereoisomer of bisoprolol are disclosed, as are compositions and formulations comprising (S)-bisoprolol. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/335,884, filed Nov. 15, 2001, the entire disclosure of which is incorporated herein by reference. Bisoprolol (1-[4-[[2-(1-methylethoxy)ethoxy]-methyl]phenoxy]-3-[(1-methylethyl)amino]-2-propanol), in its racemic form, is a commercially available drug that acts as a.beta.-adrenergic blocking agent (antagonist). The drug acts by blocking neurotransmitter action at.beta.-adrenergic receptors and, as a consequence, disrupts sympathetic nervous system transmission. The effects of.beta.-adrenergic blockade are widespread, reflecting the distribution of these receptors throughout the body. They include, but are not limited to, effects on the heart and cardiovascular system, the gastrointestinal tract, the respiratory tract, the eye, the liver, and the genitourinary system. These effects and others are described, for example, in textbooks such as Goodman and Gilman's. The Pharmacological Basis of Therapeutics (McGraw Hill, 1996) and Rang, Dale and Ritter's Pharmacology (Churchill Livingstone, 1999). The.beta.-adrenergic antagonists are indicated for a number of conditions including, but not limited to, hypertension, ischemic heart disease, atrial fibrillation, congestive heart failure, peripheral arterial occlusive disease, angina pectoris, cardiac dysrhythmias, heart failure, glaucoma, migraine, the effects of thyroid disease, and symptoms of anxiety, such as palpitations. The antagonists are most commonly used in treatment of diseases of the cardiovascular system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treatment and pharmaceutical composition Inventor(s): Ksander, Gary Michael; (Amherst, NH), Webb, Randy Lee; (Flemington, NJ) Correspondence: THOMAS HOXIE; NOVARTIS, CORPORATE INTELLECTUAL PROPERTY; ONE HEALTH PLAZA 430/2; EAST HANOVER; NJ; 07936-1080; US Patent Application Number: 20030144215 Date filed: January 14, 2003 Abstract: The invention relates a pharmaceutical composition comprising a combination of:(i) the AT 1-antagonist valsartan or a pharmaceutically acceptable salt thereof; and(ii) a NEP inhibitor or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable carrier and to a method for the treatment or prevention of a condition or diseaseselected from the group consisting of hypertension, heart failure, such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction, such as Alzheimer's, glaucoma and stroke, comprising administering a therapeutically effective amount of the pharmaceutical composition to a mammal in need thereof.


Excerpt(s): The renin angiotensin system is a complex hormonal system comprised of a large molecular weight precursor, angiotensinogen, two processing enzymes, renin and angiotensin converting enzyme (ACE), and the vasoactive mediator angiotensin II (Ang II). See J. Cardiovasc. Pharmacol., Vol. 15, Suppl. B, pp. S1-S5 (1990). The enzyme renin catalyzes the cleavage of angiotensinogen into the decapeptide angiotensin I, which has minimal biological activity on its own and is converted into the active octapeptide Ang II by ACE. Ang II has multiple biological actions on the cardiovascular system, including vasoconstriction, activation of the sympathetic nervous system, stimulation of aldosterone production, anti-natriuresis, stimulation of vascular growth and stimulation of cardiac growth. Ang II functions as a pressor hormone and is involved the pathophysiology of several forms of hypertension. The vasoconstrictive effects of angiotensin II are produced by its action on the non-striated smooth muscle cells, the stimulation of the formation of the adrenergenic hormones epinephrine and norepinephrine, as well as the increase of the activity of the sympathetic nervous system as a result of the formation of norepinephrine. Ang II also has an influence on electrolyte balance, produces, e.g., anti-natriuretic and anti-diuretic effects in the kidney and thereby promotes the release of, on the one hand, the vasopressin peptide from the pituitary gland and, on the other hand, of aldosterone from the adrenal glomerulosa. All these influences play an important part in the regulation of blood pressure, in increasing both circulating volume and peripheral resistance. Ang II is also involved in cell growth and migration and in extracellular matrix formation. Ang II interacts with specific receptors on the surface of the target cell. It has been possible to identify receptor subtypes that are termed, e.g., AT 1- and AT 2-receptors. In recent times great efforts have been made to identify substances that bind to the AT 1-receptor. Such active ingredients are often termed Ang II antagonists. Because of the inhibition of the AT 1receptor such antagonists can be used, e.g., as anti-hypertensives or for the treatment of congestive heart failure, among other indications. Ang II antagonists are therefore understood to be those active ingredients which bind to the AT 1-receptor subtype. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Non-invasive method and apparatus for cardiac pacemaker pacing parameter optimization and monitoring of cardiac dysfunction Inventor(s): Belalcazar, Hugo Andres; (Bogota, CO) Correspondence: SCHWEGMAN, LUNDBERG, WOESSNER & KLUTH, P.A.; P.O. BOX 2938; MINNEAPOLIS; MN; 55402; US Patent Application Number: 20030097158 Date filed: November 16, 2001 Abstract: Non-invasive method and apparatus for monitoring the condition of a heart failure patient and for optimizing the pacing parameters of a cardiac device implanted in a patient. A plethysmogram signal, e.g., a finger photoplethysmogram, is obtained from a patient and provided to a programmer device. The plethysmogram signal is analyzed by the programmer device to obtain a cardiac performance parameter, e.g., a pulse amplitude response, a degree of pulsus alternans, or irregularity in the pressure pulses detected in an atrial fibrillation patient. The effect on the cardiac performance parameter derived from the plethysmogram is determined for various pacing parameter values in a manner so as to reject noncardiogenic effects and artifacts. Pacing parameters resulting in the best cardiac performance parameter may be selected as the optimum pacing parameters. The programmer device may monitor a Valsalva maneuver

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performed by a patient. Optimum pacing parameters may be derived by analysis of the plethysmogram signals obtained during performance of the Valsalva maneuver using different pacing parameters. Excerpt(s): The present invention pertains generally to medical devices and more particularly to medical devices for monitoring activity of the heart and providing therapy thereto including implantable cardiac pacemakers and external programmers and other devices for determining optimal pacing parameters for such implantable pacemakers and for providing such pacing parameters to an implanted device. Various types of medical devices are employed to monitor electrical or other activity of the heart and to provide therapy to the heart for the correction of electrical conduction defects, inadequate pump function, or irregular cardiac rhythms. Such defects and irregular rhythms may result from or indicate various pathological conditions of the heart, including congestive heart failure. Many such devices are implantable beneath the skin of a patient, i.e., in the patient's chest. Such implantable devices include a hermetically sealed canister containing electronic circuitry for implementing the functions of the device, one or more electrodes implanted in one or more of the ventricles and/or atria of the heart, or in close proximity thereto, and leads for connecting the electrodes to the circuitry within the device canister. The device circuitry includes circuitry for detecting electrical signals produced by the heart, which signals are picked up at the electrodes, along with circuitry, typically implemented in a microprocessor, for analyzing the thus detected cardiac signals. The device may also include circuitry for providing therapy in the form of electrical signals applied to the heart. Such signals are provided to the heart via the leads and electrodes mounted in the heart so as to correct electrical conduction defects or abnormal rhythms. The analysis circuitry controls the delivery of such electrical therapy signals based on the detected cardiac activity signals. The implantable device may also include a transmitter/receiver for transmitting cardiac activity and other information to an external device for, e.g., storage and/or further analysis, and for receiving information, such as programming instructions, from the external device via, for example, an RF link. An example of such an implantable cardiac device is an implantable cardiac pacemaker. A pacemaker provides relatively low-level electrical pulses to the heart to stimulate heart activity when the natural cardiac rate provided by the heart is too low. A dual chamber pacemaker includes electrodes positioned in both the atria and ventricles of the heart for detecting naturally occurring atrial and ventricular activations, and for providing pacing pulses to the atria and/or ventricles as needed. Such a device monitors the time between sensed and paced atrial and ventricular activations and provides pacing pulses as needed to maintain an adequate heart rate. For example, such a device will note the occurrence of a sensed or paced atrial or ventricular event and, if a subsequent naturally occurring atrial and/or ventricular event is not sensed within a certain time (escape interval) following the first sensed or paced event, a pacing pulse will be applied to the atria and/or ventricles to maintain a desired heart rate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html


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Novel compounds for treatment of cardiac arrhythmia, synthesis, and methods of use Inventor(s): Druzgala, Pascal; (Santa Rosa, CA) Correspondence: SALIWANCHIK LLOYD & SALIWANCHIK; A PROFESSIONAL ASSOCIATION; 2421 N.W. 41ST STREET; SUITE A-1; GAINESVILLE; FL; 326066669 Patent Application Number: 20030158194 Date filed: December 10, 2002 Abstract: The subject invention pertains to novel compounds (and salts thereof), and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns methods of making the novel compounds. The novel compounds are rapidly metabolized analogs of amiodarone, having the distinct and advantageous characteristic of being metabolized to a less lipophilic compound. This results in an improved safety profile. The new compounds have particular utility for treating life-threatening ventricular tachyarrhythmias, especially in patients with congestive heart failure (CHF). The compounds also provide effective management for ventricular arrhythmias and supraventricular arrhythmias, including atrial fibrillation and re-entrant tachyarrhythmias involving accessory pathways. Excerpt(s): This application claims the benefit of provisional patent application Serial No. 60/339,898, filed Dec. 10, 2001, which is hereby incorporated by reference in its entirety. Congestive heart failure (CHF) is a disease affecting approximately 2% of the population of the United States (Sami, M. H. [1991] J. Clin. Pharmacol. 31:1081). Despite advances in the diagnosis and treatment of CHF, the prognosis remains poor with a 5year mortality rate higher than 50% from the time of diagnosis (McFate Smith, W. [1985] Am. J. Cardiol. 55:3A; McKee, P. A., W. P. Castelli, P. M. McNamara, W. B. Kannel [1971] N. Engl. J. Med. 285:1441). In patients with CHF, the rate of survival is lowest in those patients with severe depression of left ventricular function and patients who have frequent ventricular arrhythmias. Patients with ventricular arrhythmias and ischemic cardiomyopathy have an increased risk of sudden death. The presence of ventricular tachycardia in patients with severe CHF results in a three-fold increase in sudden death compared to those without tachycardia (Bigger, J. T., Jr. [1987] Circulation 75 (Supplement IV):28). Because of the high prevalence of sudden unexpected death in patients with CHF, there has been a growing interest in the prognostic significance of arrhythmias in these patients. Several compounds have been used in the management of cardiac arrhythmias in patients with congestive heart failure. Unfortunately, antiarrhythmic drug therapy has been disappointing. The efficacy of anti-arrhythmic drugs markedly decreases as left ventricular function declines, such that only a small fraction of patients with CHF are responsive to anti-arrhythmic therapy. No anti-arrhythmic drug has prevented sudden death in patients with CHF. There is even a question of increased mortality associated with certain anti-arrhythmic drugs (the CAST investigators [1989] N. Engl. J. Med. 321:406). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel nucleic acid molecules and polypeptides encoding baboon TAFI Inventor(s): Hsu, Mei-Yin; (Hillsboro, NJ), Matsueda, Gary R.; (Princeton, NJ), Nayeem, Akbar; (Newtown, PA), Tamura, James K.; (Yardley, PA) Correspondence: STEPHEN B. DAVIS; BRISTOL-MYERS SQUIBB COMPANY; PATENT DEPARTMENT; P O BOX 4000; PRINCETON; NJ; 08543-4000; US Patent Application Number: 20030215850 Date filed: March 4, 2003 Abstract: The present invention relates to the isolation and identification of novel baboon nucleic acid molecules and proteins and polypeptides encoded by such nucleic acid molecules, or degenerate variants thereof, which proteins and polypeptides comprise novel baboon thrombin-activatable fibrinolysis inhibitors or "TAFI" enzyme molecules. Because the novel baboon TAFI proteins and polypeptides of the invention inhibit the breakdown of blood clots, they may be therapeutically useful for the treatment of blood disorders wherein clotting needs to be regulated or promoted, such as hemophilia or von Willebrand's disease or in other situations, such as trauma, wherein blood clotting or coagulation needs to be regulated or promoted. The sequences of the invention are also useful in screening methods for the identification of compounds that modulate the expression of the baboon TAFI nucleic acids and/or the activity of the baboon TAFI proteins and polypeptides of the invention. Such agonist or antagonist compounds may be useful in the treatment of various blood clotting disorders and conditions requiring hemostatic control such as hemophilia or various thrombotic diseases such as deep venous thrombosis, coronary artery disease, stroke associated with atrial fibrillation and recurrent thrombosis following stroke or myocardial infarction. Excerpt(s): This application is a continuation-in-part Application of and claims benefit to provisional application U.S. Serial No. 60/361,523 filed Mar. 4, 2002, under 35 U.S.C. 119(e). The entire teachings of the referenced application are incorporated herein by reference. The sequences of the invention are also useful in screening methods for the identification of compounds that modulate the expression of the baboon TAFI nucleic acids and/or the activity of the baboon TAFI proteins and polypeptides of the invention. Such agonist or antagonist compounds may be useful in the treatment of various blood clotting disorders and conditions requiring hemostatic control such as hemophilia or various thrombotic diseases such as deep venous thrombosis, coronary artery disease, stroke associated with atrial fibrillation and recurrent thrombosis following stroke or myocardial infarction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Ortho, ortho-substituted nitrogen-containing bisaryl compounds, processes for their preparation, their use as medicaments, and pharmaceutical preparation comprising them Inventor(s): Brendel, Joachim; (Bad Vilbel, DE), Hemmerle, Horst; (Bad Soden, DE), Kleemann, Heinz-Werner; (Bischofsheim, DE), Peukert, Stefan; (Frankfurt, DE) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030060470 Date filed: December 5, 2001


Abstract: Ortho, ortho-substituted nitrogen-containing bisaryl compounds, processes for their preparation, their use as medicaments, and pharmaceutical preparations including their use as antiarrhythmic active compounds, for example, for the treatment and prophylaxis of atrial arrhythmias, e.g. atrial fibrillation (AF) or atrial flutters. Compounds of the invention include compounds of the formula I 1 Excerpt(s): This application claims the benefit of foreign priority under 35 U.S.C.sctn.119 of German patent application no. 10060807.8-44, filed on Dec. 7, 2000 the contents of which are incorporated by reference herein. The present invention relates to ortho, ortho-substituted nitrogen-containing bisaryl compounds. Embodiments of the invention include processes for their preparation, their use as medicaments, and pharmaceutical preparations comprising them. substituted or unsubstituted biphenylyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl or a substituted or unsubstituted N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, where the substituted phenyl, substituted naphthyl, substituted biphenylyl, substituted furyl, substituted thienyl and the substituted N-containing heteroaromatic are each independently substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF.sub.3, OCF.sub.3, NO.sub.2, CN, COOMe, CONH.sub.2, COMe, NH.sub.2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R(13) is hydrogen; R(2) is hydrogen or methyl; R(3) is C.sub.yH.sub.2y--R(16); where y is 0, 1, 2, 3 or 4; and y cannot be 0 if R(16) is OR(17); R(16) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, carbon atoms, CF.sub.3, OR(17), SO.sub.2Me, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl or a substituted or unsubstituted N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, where the substituted phenyl, substituted naphthyl, substituted furyl, substituted thienyl and the substituted N- containing heteroaromatic are each independently substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF.sub.3, NO.sub.2, OCF.sub.3, CN, COOMe, CONH.sub.2, COMe, NH.sub.2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R(17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF.sub.3, substituted phenyl, unsubstituted phenyl, substituted 2-, 3- or 4- pyridyl, or unsubstituted 2-, 3- or 4pyridyl where the substituted phenyl or substituted 2-, 3- or 4- pyridyl are each independently substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF.sub.3, NO.sub.2, CN, COOMe, CONH.sub.2, COMe, NH.sub.2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R(4) is hydrogen or alkyl having 1 or 2 carbon atoms; R(5) is independently of one another chosen from F, Cl, Br, I, CF.sub.3, NO.sub.2, CN, COOMe, CONH.sub.2, COMe, NH.sub.2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino; R(30) and R(31) independently of one another are hydrogen or methyl; and their pharmaceutically acceptable salts In another embodiment, the compounds of the formula I are those in which A4 is nitrogen and A1, A2, A3, A5, A6, A7 and A8 independently of one another are chosen from CH and CR(5), where at least 5 of these groups are CH; and their pharmaceutically acceptable salts. In an even further embodiment, the compounds of the formula I are those in which: R(1) is C(O)OR(9), SO.sub.2R(10), COR(11) or C(O)NR(12)R(13); where R(9), R(10), R(11) and R(12) independently of one another are C.sub.xH.sub.2x--R(14); where x is 0, 1, 2 or 3; R(14) is alkyl having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 carbon atoms, CF.sub.3, substituted phenyl, unsubstituted phenyl, substituted

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pyridyl, or unsubstituted pyridyl where the substituted phenyl and substituted pyridyl are each independently substituted by 1 or 2 substituents chosen from F, Cl, Br, I, CF.sub.3, OCF.sub.3, OH, alkyl having 1, 2 or 3 carbon atoms or alkoxy having 1 or 2 carbon atoms; R(13) is hydrogen; R(2) is hydrogen; R(3) is C.sub.yH.sub.2y--R(16); y is 0, 1 or 2; R(16) is alkyl having 1, 2, 3 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF.sub.3, substituted phenyl, unsubstituted phenyl, substituted pyridyl, or unsubstituted pyridyl where the substituted phenyl and substituted pyridyl are each independently substituted by 1 or 2 substituents chosen from F, Cl, CF.sub.3, alkyl having 1, 2 or 3 carbon atoms and alkoxy having 1 or 2 carbon atoms; R(4) is hydrogen; R(5) is independently of one another chosen from F, Cl, CF.sub.3, CN, COOMe, CONH.sub.2, COMe, NH.sub.2, OH, alkyl having 1, 2 or 3 carbon atoms and alkoxy having 1 or 2 carbon atoms; R(30) and R(31) independently of one another are hydrogen or methyl; and their pharmaceutically acceptable salts. Another example of the compounds of the formula I are those in which: R(1) is C(O)OR(9) or COR(11); R(9) and R(11) independently of one another are C.sub.xH.sub.2x--R(14); where x is 0, 1, 2 or 3; R(14) is cycloalkyl having 5 or 6 carbon atoms substituted phenyl, or unsubstituted phenyl where the substituted phenyl is substituted by 1 or 2 substituents chosen from F, Cl, Br, I, CF.sub.3, OCF.sub.3, OH, alkyl having 1, 2 or 3 carbon atoms or alkoxy having 1 or 2 carbon atoms; R(2) is hydrogen; R(3) is C.sub.yH.sub.2y--R(16); y is 0, 1 or 2; R(16) is alkyl having 1, 2 or 3 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, substituted phenyl, unsubstituted phenyl, substituted pyridyl, or unsubstituted pyridyl, where the substituted phenyl and substituted pyridyl are each independently substituted by 1 or 2 substituents chosen from F, Cl, CF.sub.3, OCF.sub.3, alkyl having 1, 2 or 3 carbon atoms and alkoxy having 1 or 2 carbon atoms; R(4) is hydrogen; R(5) is independently of one another chosen from F, Cl, alkyl having 1, 2, 3 carbon atoms and alkoxy having 1 or 2 carbon atoms; R(30) and R(31) are hydrogen; and their pharmaceutically acceptable salts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Permanent Atrial-His-Ventricular sequential pacing Inventor(s): Casavant, David A.; (Reading, MA) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030078625 Date filed: October 23, 2001 Abstract: A method and apparatus for cardiac pacing and, more particularly, for AtrialHis-Ventricular sequential pacing to improve sino-atrial node dysfunction or heart block superior to the His bundle. As a derivative, His-Ventricular sequential pacing can be employed to treat permanent atrial fibrillation. Excerpt(s): The present invention relates to a method and apparatus for cardiac pacing and, more particularly, for Atrial-His-Ventricular sequential pacing to improve sinoatrial node dysfunction or heart block superior to the His bundle. As a derivative, His-Ventricular sequential pacing can be employed to treat permanent atrial fibrillation. The sinoatrial (SA) node represents the natural pacemaker that controls the rhythmic electrical excitation in a normal human heart. At an appropriate time, an electrical impulse arising from the SA node is transmitted to the right and left atrial chambers. This impulse causes muscle tissue surrounding the atrium to depolarize and contract which generates an electrical signal known as a P-wave. The same electrical


impulse arising from the SA node also travels to the right and left ventricles through the atrioventricular (AV) node and atrioventricular (AV) bundle. The AV node, situated in the lower portion of the right atrium, receives the impulse to contract. The impulse is then transmitted through the AV bundle comprising Common Bundle of His (His bundle), right and left bundle branches, and Purkinje fibers that cover most of the endocardial surface of the ventricles. The ventricular muscle tissue depolarizes, generating an R-wave, then contracts. This forces blood held in the ventricles through the arteries and to various body locations. This action is repeated in a rhythmic cycle in which the atrial and ventricular chambers alternately contract and pump, then relax and fill. Disturbances of impulse formation by the sinus node and/or AV conduction block due to disease and aging are commonly treated by artificial pacing. An artificial pacemaker is an implantable medical device that monitors the activity of the heart for the occurrence of P- and/or R-waves. When a P- or R-wave is not sensed after a prescribed period of time, the pacemaker electronically generates stimuli in order to force the depolarization of the atria and/or ventricles. A pacemaker-generated stimulus that is delivered to the atria is known as an A-pulse, whereas a stimulus delivered to the ventricles is a V-pulse. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

System and method for magnetic-resonance-guided electrophysiologic and ablation procedures Inventor(s): Atalar, Ergin; (Columbia, MD), Berger, Ronald D.; (Baltimore, MD), Calkins, Hugh; (Baltimore, MD), Halperin, Henry R.; (Baltimore, MD), Lardo, Albert; (Baldwin, MD), Lima, Joao; (Timonium, MD), McVeigh, Elliot R.; (Potomac, MD) Correspondence: NIXON & VANDERHYE, PC; 1100 N GLEBE ROAD; 8TH FLOOR; ARLINGTON; VA; 22201-4714; US Patent Application Number: 20030199755 Date filed: April 28, 2003 Abstract: A system and method for using magnetic resonance imaging to increase the accuracy of electrophysiologic procedures is disclosed. The system in its preferred embodiment provides an invasive combined electrophysiology and imaging antenna catheter which includes an RF antenna for receiving magnetic resonance signals and diagnostic electrodes for receiving electrical potentials. The combined electrophysiology and imaging antenna catheter is used in combination with a magnetic resonance imaging scanner to guide and provide visualization during electrophysiologic diagnostic or therapeutic procedures. The invention is particularly applicable to catheter ablation, e.g., ablation of atrial fibrillation. In embodiments which are useful for catheter ablation, the combined electrophysiology and imaging antenna catheter may further include an ablation tip, and such embodiment may be used as an intracardiac device to both deliver energy to selected areas of tissue and visualize the resulting ablation lesions, thereby greatly simplifying production of continuous linear lesions. The invention further includes embodiments useful for guiding electrophysiologic diagnostic and therapeutic procedures other than ablation. Imaging of ablation lesions may be further enhanced by use of MR contrast agents. The antenna utilized in the combined electrophysiology and imaging catheter for receiving MR signals is preferably of the coaxial or "loopless" type. High-resolution images from the antenna may be combined with low-resolution images from surface coils of the MR scanner to produce a composite image. The invention further provides a system for eliminating the pickup of

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RE energy in which intracardiac wires are detuned by filtering so that they become very inefficient antennas. An RF filtering system is provided for suppressing the MR imaging signal while not attenuating the RF ablative current. Steering means may be provided for steering the invasive catheter under MR guidance. Other ablative methods can be used such as laser, ultrasound, and low temperatures. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/106,965 filed Nov. 4, 1998, the entire disclosure of which is incorporated herein by reference. The invention relates in general to ablation and electrophysiologic diagnostic and therapeutic procedures, and in particular to systems and methods for guiding and providing visualization during such procedures. Atrial fibrillation and ventricular tachyarrhythmias occurring in patients with structurally abnormal hearts are of great concern in contemporary cardiology. They represent the most frequently encountered tachycardias, account for the most morbidity and mortality, and, despite much progress, remain therapeutic challenges. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Transmural ablation tool and method Inventor(s): Pendekanti, Rajesh; (Bridgewater, NJ), Wellman, Parris S.; (Hillsborough, NJ) Correspondence: NUTTER MCCLENNEN & FISH LLP; WORLD TRADE CENTER WEST; 155 SEAPORT BOULEVARD; BOSTON; MA; 02210-2604; US Patent Application Number: 20030069572 Date filed: September 28, 2001 Abstract: An ablation method and device contacts one surface of a target layer and positions the tissue to ablate entirely through the layer. The tissue may be a wall of the heart (ablated, for example, to form blocking lesions for atrial fibrillation), and ablation may be performed with the heart stopped or beating, and effected by either endocardial or epicardial contact. Access may be through an open incision or a minimally invasive technique involving a small opening through which one or more elongated surgical tools are inserted. Illustratively, an atrial ablation treatment can be performed prophylactically (after CABG), or independently to treat an existing condition. A tool of the present invention has a handle at a proximal end, a bipolar ablation head, and an elongated body interconnecting the handle and the ablation head. A channel or contoured surface fixes and bends the tissue such that inter-electrode conduction paths span the thickness of the layer, thus dependably creating a fully transmural ablation lesion. The oriented transmural energy conduction paths reduce the possibility of inducing coagulation of blood in the heart chamber. One bipolar assembly has an electrode spacing of approximately ten millimeters across a channel of about five millimeters depth. Preferably the ablation head forms a suction holder, connected through internal passages to a vacuum pressure of about 100-500 mmHg, and immobilizes the contacted tissue. Excerpt(s): The present invention relates to tissue ablation and more particularly to methods and devices for creating effective ablation extending entirely through a layer of tissue. It has particular application to methods and devices for ablating foci and for forming conduction blocking lesions in a wall of the heart. Over the last decade, the field of electrophysiology, especially mapping and treatment of arrhythmias of the heart, has grown spectacularly. A great number of ablation tools and catheters have been devised,


and procedures have been methodically tested employing a number of catheter-like ablation devices, often with structures specifically constructed to enable the instrument to place a specific lesion at a site or region. Among catheter-based cardiac interventional techniques, the most common employ either high frequency (RF) electrical energy or cryogenic cooling to ablate tissue and cause scarring. Other available catheters employ laser illumination, microwave energy or heated surface contact to ablate tissue at a region or along a path operative to destroy aberrant tissue or disconnect an aberrant conduction pathway. These cardiac treatment methods require mapping of the aberrant foci within the heart, and then selective ablation of foci, or lines that isolate the foci, in the heart wall. Such ablation treatment is generally a time-consuming and complex procedure. Each of these approaches has its own particular advantages and constraints. Thus, for example, basket catheter constructions are intended for delivery (typically along an endovascular route) into a cardiac chamber, and seek to provide an expanded electrode structure that may maintain itself in fixed contact with the endocardial wall of a still-beating heart for protracted time periods, so that mapping and ablation operations may be carried out in a fixed frame of reference at plural discrete points or along discrete arcs or segments. Still other catheters may have ablation tips with a particular geometry effective to provide oriented arc or segment lesions. Many common catheter devices act as drag electrodes with an ablation tip that "draws" lines of conduction block, ablating tissue at its point of contact as the tip is moved along the heart wall, allowing greater flexibility in placement, but at the expense of stability of positioning. Such catheter tips may require (and include) one or more barbs or prongs that penetrate the cardiac wall to anchor the ablation tip assembly. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Ventricular pacing for prevention of atrial fibrillation Inventor(s): Wagner, Darrell O.; (Isanti, MN) Correspondence: SCHWEGMAN, LUNDBERG, WOESSNER & KLUTH, P.A.; P.O. BOX 2938; MINNEAPOLIS; MN; 55402; US Patent Application Number: 20030125775 Date filed: January 3, 2002 Abstract: A method and apparatus for preventing atrial fibrillation arising from a premature atrial contraction. Upon detection of a premature atrial contraction, a pace is delivered to a ventricle at a specified AV interval selected as either a late-pace or earlypace value. The resulting ventricular depolarization then occurs during a time when the atria are not vulnerable to the triggering of fibrillation. Excerpt(s): This invention pertains to systems and methods for cardiac rhythm management. In particular, the invention relates to cardiac pacemakers and their methods of operation. Tachyarrhythmias are abnormal heart rhythms characterized by a rapid heart rate, typically expressed in units of beats per minute (bpm). They can occur in either chamber of the heart (i.e., ventricles or atria) or both. Examples of tachyarrhythmias include sinus tachycardia, ventricular tachycardia, ventricular fibrillation (VF), atrial tachycardia, and atrial fibrillation (AF). Tachycardia is characterized by a rapid rate, either due to an ectopic excitatory focus or abnormal excitation by normal pacemaker tissue, while fibrillation occurs when the chamber depolarizes in a chaotic fashion with abnormal depolarization waveforms as reflected by an EKG. An electrical shock applied to a heart chamber (i.e., defibrillation or cardioversion) can be used to terminate most tachyarrhythmias by depolarizing

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excitable myocardium, which thereby prolongs refractoriness, interrupts reentrant circuits, and discharges excitatory foci. Implantable cardioverter/defibrillators (ICDs) provide this kind of therapy by delivering a shock pulse to the heart when fibrillation is detected by the device. ICDs can be designed to treat either atrial or ventricular tachyarrhythmias, or both, and may also incorporate cardiac pacing functionality. The most dangerous tachyarrhythmias are ventricular tachycardia and ventricular fibrillation, and ICDs have most commonly been applied in the treatment of those conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Ventricular rate stabilization Inventor(s): Bout, Wim; (Dieren, NL), Corbucci, Giorgio; (Cento (FE) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030199935 Date filed: April 22, 2002 Abstract: Techniques for stabilizing the rate of a ventricle, during conducted atrial fibrillation for example, adjust the escape interval of an implantable medical device to increase or decrease the pacing rate. In some embodiments, the escape interval is adjusted to achieve and maintain a percentage of pacing. In other embodiments, the stability of the ventricular rate is quantified as a function of measured R-R intervals, and the escape interval is adjusted to achieve and maintain a level of stability. In still other embodiments, a mean compensatory pause length is determined, and the escape interval is adjusted as a function of the mean compensatory pause length, to maintain the escape interval at or near the mean compensatory pause length. Excerpt(s): The present invention relates generally to cardiac pacemakers, and more particularly to cardiac pacemakers having a ventricular escape interval that can be adjusted to stabilize the ventricular rate. When functioning properly, a heart maintains its own intrinsic rhythm, and is capable of pumping adequate blood throughout a circulatory system. This intrinsic rhythm is a function of intrinsic signals generated by the sinoatrial node, or SA node, located in the upper right atrium. The SA node periodically depolarizes, which in turn causes the atrial heart tissue to depolarize such that right and left atria contract as the depolarization travels through the atrial heart tissue. The atrial depolarization signal is also received by the atrioventricular node, or AV node, which, in turn, triggers a subsequent ventricular depolarization signal that travels through and depolarizes the ventricular heart tissue causing the right and left ventricles to contract. Some patients, however, have irregular cardiac rhythms, referred to as cardiac arrhythmias. Cardiac arrhythmias result in diminished blood circulation because of diminished cardiac output. Atrial fibrillation is a common cardiac arrhythmia that reduces the pumping efficiency of the heart. Atrial fibrillation is characterized by rapid, irregular, uncoordinated depolarizations of the atria. These depolarizations may not originate from the SA node, but may instead originate from an arrhythmogenic substrate, such as an ectopic focus, within the atrial heart tissue. The reduced pumping efficiency due to atrial fibrillation requires the ventricle to work harder, which is particularly undesirable in sick patients that cannot tolerate additional stresses. As a result of atrial fibrillation, patients must typically limit activity and exercise.


Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with atrial fibrillation, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “atrial fibrillation” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on atrial fibrillation. You can also use this procedure to view pending patent applications concerning atrial fibrillation. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON ATRIAL FIBRILLATION Overview This chapter provides bibliographic book references relating to atrial fibrillation. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on atrial fibrillation include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “atrial fibrillation” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “atrial fibrillation” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “atrial fibrillation” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

ABC of Atrial Fibrillation by G. Y. Lip (Editor); ISBN: 0727910701; http://www.amazon.com/exec/obidos/ASIN/0727910701/icongroupinterna

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Acute Management of Atrial Fibrillation and Flutter (Round Table Series (RTS)) by A. Camm (Editor); ISBN: 1853153206; http://www.amazon.com/exec/obidos/ASIN/1853153206/icongroupinterna

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Atrial Fibrillation by A. John Camm, et al (1999); ISBN: 1853177156; http://www.amazon.com/exec/obidos/ASIN/1853177156/icongroupinterna

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Atrial Fibrillation (1991); ISBN: 3540196994; http://www.amazon.com/exec/obidos/ASIN/3540196994/icongroupinterna

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Atrial Fibrillation by John Rawles; ISBN: 0387196994; http://www.amazon.com/exec/obidos/ASIN/0387196994/icongroupinterna


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Atrial Fibrillation by David Martin, et al; ISBN: 0865421005; http://www.amazon.com/exec/obidos/ASIN/0865421005/icongroupinterna

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Atrial Fibrillation : My Heart, the Doctors, and Me by E. A. Butler (2000); ISBN: 0967520304; http://www.amazon.com/exec/obidos/ASIN/0967520304/icongroupinterna

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Atrial Fibrillation after Cardiac Surgery (DEVELOPMENTS IN CARDIOVASCULAR MEDICINE Volume 222) by Jonathan S. Steinberg (Editor); ISBN: 0792386558; http://www.amazon.com/exec/obidos/ASIN/0792386558/icongroupinterna

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Atrial Fibrillation for the Clinician by Francis D. Murgatroyd, A. John Camm; ISBN: 0879936142; http://www.amazon.com/exec/obidos/ASIN/0879936142/icongroupinterna

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Atrial Fibrillation in Clinical Practice by Gregory Y. H. Lip; ISBN: 1853178950; http://www.amazon.com/exec/obidos/ASIN/1853178950/icongroupinterna

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Atrial Fibrillation in Practice (In Practice) by G.Y.H. Lip; ISBN: 1853154849; http://www.amazon.com/exec/obidos/ASIN/1853154849/icongroupinterna

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Atrial Fibrillation: A Treatable Disease? (Developments in Cardiovascular Medicine, 139) by Jan Herre Kingma (Editor), et al (1992); ISBN: 0792320085; http://www.amazon.com/exec/obidos/ASIN/0792320085/icongroupinterna

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Atrial Fibrillation: Facts from Yesterday, Ideas for Tomorrow (The Bakken Research Center Series; V. 8) by Henri E. Kulbertus (1994); ISBN: 0879930977; http://www.amazon.com/exec/obidos/ASIN/0879930977/icongroupinterna

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Atrial Fibrillation: Mechanisms and Management by Rodney H., Md. Falk (Editor), Philip J., Md. Podrid (Editor); ISBN: 039751767X; http://www.amazon.com/exec/obidos/ASIN/039751767X/icongroupinterna

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Atrial Fibrillation: Mechanisms and Therapeutic Strategies by S. Bertil Olsson, et al; ISBN: 0879935871; http://www.amazon.com/exec/obidos/ASIN/0879935871/icongroupinterna

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Atrial Flutter and Fibrillation: From Basic to Clinical Applications by Nadir Saoudi (Editor), et al; ISBN: 0879936614; http://www.amazon.com/exec/obidos/ASIN/0879936614/icongroupinterna

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Cardiac arrhythmias : the management of atrial fibrillation; ISBN: 3540555889; http://www.amazon.com/exec/obidos/ASIN/3540555889/icongroupinterna

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Cardiac Arrhythmias: The Management of Atrial Fibrillation by R. W. F. Campbell, Michiel Johannes Janse; ISBN: 0387555889; http://www.amazon.com/exec/obidos/ASIN/0387555889/icongroupinterna

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Evaluation of New Non-Pharmacologial Therapies for Symptomatic Atrial Fibrillation: With Special Emphasis on the Maza Procedure (Comprehensive Summaries of Uppsala Dissertations from the Faculty of mediciNe, 1113) by Stefan Lonnerholm (2002); ISBN: 9155452159; http://www.amazon.com/exec/obidos/ASIN/9155452159/icongroupinterna

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Hybrid Therapy for Atrial Fibrillation - Catheter ablation: Hype or Hope? [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3WE; http://www.amazon.com/exec/obidos/ASIN/B00008R3WE/icongroupinterna

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Lone Atrial Fibrillation: Towards a Cure by Hans R. Larsen (2002); ISBN: 0968637515; http://www.amazon.com/exec/obidos/ASIN/0968637515/icongroupinterna

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Nonpharmacological Management of Atrial Fibrillation by Francis D. Murgatroyd (Editor), A. John Camm (Editor); ISBN: 0879936657; http://www.amazon.com/exec/obidos/ASIN/0879936657/icongroupinterna

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Pulmonary Vein Recordings: A Practical Guide to the Mapping & Ablation of Atrial Fibrillation by Laurent Macle; ISBN: 1901346412; http://www.amazon.com/exec/obidos/ASIN/1901346412/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “atrial fibrillation” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Ambulatory care stroke prevention and treatment initiative: management of atrial fibrillation: final report, September 1997. Author: Center for Clinical Quality Evaluation.; Year: 1992; Washington, DC: Center for Clinical Quality Evaluation, [1997]

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Analysis of the acoustic spectral signiture of prosthetic heart valves in patients experiencing atrial fibrillation [microform] Author: Scott, David D.; Year: 1997; [Livermore, CA: Lawrence Livermore National Laboratory, 1994]

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Anticoagulation for stroke prevention in chronic non-valvular atrial fibrillation Author: Green, C. J.; Year: 1995; Vancouver, British Columbia, Canada: BCOHTA CHSPR, 1995; ISBN: 1896256023 http://www.amazon.com/exec/obidos/ASIN/1896256023/icongroupinterna

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Atrial fibrillation Author: Morris, Douglas C.; Year: 1994; Chicago: Year Book Medical, 1980; ISBN: 0815199155 http://www.amazon.com/exec/obidos/ASIN/0815199155/icongroupinterna

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Atrial fibrillation: mechanisms and management Author: Falk, Rodney H.; Year: 1997; New York: Raven Press, c1992; ISBN: 0881678317

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Atrial fibrillation: proceedings of a symposium held in Kiruna, Sweden, June 24-27, 1981 Author: Kulbertus, H. E. (Henri E.); Year: 1982; Mölndal, Sweden: Hässle, 1982; ISBN: 918552025X

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Atrial fibrillation, etiology, course, and prognosis: a follow-up study of 1212 cases Author: Godtfredsen, John.; Year: 1975; Copenhagen: [s.n.], 1975

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Early and late results of conversion of atrial fibrillation with quinidine; a clinical and hemodynamic study. Author: Cramér, Gun.; Year: 1974; Göteborg, 1968

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Investigations into respiratory and haemodynamic changes following pulmonary surgery; with special reference to the aetiology of postoperative atrial fibrillation.

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.


[Translated from the Danish. Author: Alstrup, Poul.; Year: 1951; Odense] Odense Univ. Press, 1974; ISBN: 8774920987 http://www.amazon.com/exec/obidos/ASIN/8774920987/icongroupinterna •

Stroke prevention through management of atrial fibrillation: a guide for changing practice patterns. Author: Center for Clinical Quality Evaluation.; Year: 1992; Washington, DC: Center for Clinical Quality Evaluation, [1997?]

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The use of meta-analysis in a technology assessment: warfarin for stroke prevention in atrial fibrillation Author: Green, C. J.; Year: 1995; Vancouver, British Columbia, Canada: BCOHTA CHSPR, 1997

Chapters on Atrial Fibrillation In order to find chapters that specifically relate to atrial fibrillation, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and atrial fibrillation using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “atrial fibrillation” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on atrial fibrillation: •

Stroke and Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 449-456. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail: [email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on stroke and diabetes is from a compilation and assessment of data on diabetes and its complications in the United States. Diabetes is more common in the African American population than in the white population in the United States and contributes to the increased risk of stroke among African Americans. Persons with diabetes may have a worse prognosis after a stroke. Elevated blood pressure is the major risk factor for stroke. Other risk factors for stroke, besides diabetes, include cigarette smoking and a high level of low density lipoprotein (LDL) cholesterol. Stroke is substantially increased in individuals who have other vascular diseases, especially coronary heart disease, left ventricular hypertrophy, atrial fibrillation, and peripheral vascular disease. The author maintains that preventing stroke in people with diabetes is feasible through identifying and treating risk factors, especially hypertension, cigarette smoking, and high LDL cholesterol. It is unknown whether reduction of blood glucose levels by either pharmacologic or nonpharmacologic methods will reduce the risk of stroke. It is also possible to identify individuals with atherosclerosis and to more aggressively intervene to reduce the risk of stroke by a combination of therapies. 6 figures. 6 tables. 32 references. (AA-M).

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CHAPTER 8. MULTIMEDIA ON ATRIAL FIBRILLATION Overview In this chapter, we show you how to keep current on multimedia sources of information on atrial fibrillation. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Atrial Fibrillation The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in atrial fibrillation (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on atrial fibrillation: •

Atrial fibrillation [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1981; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1981

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Atrial fibrillation [videorecording]. Year: 2003; Format: Videorecording; Timonium, MD: Milner-Fenwick, 2003

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Atrial fibrillation and flutter [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital, [and] Marshfield Medical Research Foundation; Year: 1993; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, [1993]

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Current concepts in the treatment of atrial fibrillation and flutter [videorecording] Source: produced by Virginia Hospital Television Network, Office of Medical Education, Medical College of Virginia/Virginia Commonwealth University; Year: 1992; Format: Videorecording; Richmond, Va.: The University, c1992

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Current concepts in the treatment of atrial fibrillation and flutter [videorecording] Source: produced by Virginia Hospital Television Network, Office of Medical


Education, Medical College of Virginia/Virginia Commonwealth University; Year: 1992; Format: Videorecording; Richmond, Va.: Virginia Commonwealth University, c1992 •

Management of atrial fibrillation [videorecording]: sudden cardiac death Source: produced by Heart House Learning Center & Heart House Digital; Year: 1998; Format: Videorecording; Bethesda, MD: American College of Cardiology, 1998

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Nonvalvular atrial fibrillation [videorecording]: a management dilemma Source: with Michael D. Ezekowitz; Year: 1990; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1990

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Premature atrial contractions, atrial flutter, and atrial fibrillation [filmstrip] Source: Trainex Corporation; Year: 1971; Format: Filmstrip; [Garden Grove, Calif.]: Trainex, c1971

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The Maze IV procedure for atrial fibrillation [videorecording]: a simplified operation using bipolar radiofrequency ablation Source: American College of Surgeons; produced by Ciné-Med; Year: 2002; Format: Videorecording; [Woodbury, Conn.]: CinéMed, c2002

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The Maze-III procedure for atrial fibrillation [videorecording] Source: produced by Ciné-Med; Year: 1992; Format: Videorecording; [Wayne, N.J.]: American Cyanamid, c1992

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CHAPTER 9. PERIODICALS AND NEWS ON ATRIAL FIBRILLATION Overview In this chapter, we suggest a number of news sources and present various periodicals that cover atrial fibrillation.

News Services and Press Releases One of the simplest ways of tracking press releases on atrial fibrillation is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “atrial fibrillation” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to atrial fibrillation. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “atrial fibrillation” (or synonyms). The following was recently listed in this archive for atrial fibrillation: •

Mortality rate high among dialysis patients with atrial fibrillation Source: Reuters Medical News Date: October 28, 2003


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Inadequate anticoagulation in atrial fibrillation patients raises stroke severity Source: Reuters Industry Breifing Date: September 10, 2003

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Longitudinal conduction indicates ablation sites for atrial fibrillation treatment Source: Reuters Medical News Date: August 06, 2003

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Hospitalizations for atrial fibrillation increasing at "dramatic" rate Source: Reuters Medical News Date: July 28, 2003

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Ablation therapy may be more effective than drugs for atrial fibrillation Source: Reuters Medical News Date: July 15, 2003

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FDA advisors reject Cardima's atrial fibrillation device Source: Reuters Industry Breifing Date: May 29, 2003

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Characteristics of atrial fibrillation requiring cardioversion identified Source: Reuters Medical News Date: May 05, 2003

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Left atrial thrombus is associated with TIA in patients with atrial fibrillation Source: Reuters Medical News Date: April 24, 2003

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Exanta tops warfarin for patients with atrial fibrillation Source: Reuters Industry Breifing Date: April 03, 2003

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Long-term statin use lowers risk of atrial fibrillation Source: Reuters Medical News Date: April 01, 2003

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Metoprolol reduces risk of atrial fibrillation after cardiac surgery Source: Reuters Industry Breifing Date: March 14, 2003

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Pulmonary vein isolation can be helpful in persistent atrial fibrillation Source: Reuters Medical News Date: February 07, 2003

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Extended-release propafenone helpful in paroxysmal atrial fibrillation Source: Reuters Industry Breifing Date: January 17, 2003

•

Potassium channel gene mutation associated with familial atrial fibrillation Source: Reuters Medical News Date: January 09, 2003

•

Bristol-Myers, Icagen extend atrial fibrillation collaboration Source: Reuters Industry Breifing Date: December 20, 2002

•

Dual-chamber ICD pacing detrimental for some patients with atrial fibrillation Source: Reuters Industry Breifing Date: December 19, 2002

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•

Rate control effective for atrial fibrillation Source: Reuters Medical News Date: December 04, 2002

•

Oral anticoagulants more effective than aspirin at reducing atrial fibrillation-related stroke risk Source: Reuters Industry Breifing Date: November 20, 2002

•

St. Jude, Novation ink purchasing deal for atrial fibrillation technology Source: Reuters Industry Breifing Date: November 18, 2002

•

Atrial fibrillation common among ER patients, often untreated Source: Reuters Medical News Date: November 04, 2002

•

Increased mortality risk seen with atrial fibrillation, especially in women Source: Reuters Medical News Date: October 29, 2002

•

Biatrial pacing effective in controlling paroxysmal atrial fibrillation Source: Reuters Medical News Date: August 23, 2002

•

Two amiodarone regimens reduce atrial fibrillation risk after open-heart surgery Source: Reuters Industry Breifing Date: August 12, 2002

•

Verapamil improves success of second cardioversion for atrial fibrillation Source: Reuters Industry Breifing Date: August 07, 2002

•

Biphasic shock waveform advantageous in cardioversion of atrial fibrillation Source: Reuters Medical News Date: July 09, 2002

•

Cardioversion of atrial fibrillation normalizes atrial natriuretic peptide levels Source: Reuters Medical News Date: June 28, 2002

•

Addition of irbesartan to amiodarone reduces recurrence of atrial fibrillation Source: Reuters Industry Breifing Date: June 24, 2002

•

Long-term participation in sports seems to predispose men to atrial fibrillation Source: Reuters Medical News Date: April 10, 2002

•

Pulmonary vein isolation is safe, curative for atrial fibrillation Source: Reuters Medical News Date: March 20, 2002

•

Rate control deemed "primary strategy" for managing atrial fibrillation Source: Reuters Industry Breifing Date: March 18, 2002

•

Biphasic waveform cardioversion effective for refractory atrial fibrillation Source: Reuters Industry Breifing Date: January 18, 2002


•

Cardiome initiates pivotal phase II atrial fibrillation trial Source: Reuters Industry Breifing Date: January 17, 2002

•

High relapse rate observed after electrical cardioversion for atrial fibrillation Source: Reuters Medical News Date: December 26, 2001

•

Warfarin underused in atrial fibrillation patients in long-term care Source: Reuters Medical News Date: November 12, 2001

•

Risk factor for atrial fibrillation recurrence identified Source: Reuters Medical News Date: November 07, 2001

•

Icagen, Bristol-Myers extend deal to develop atrial fibrillation therapy Source: Reuters Industry Breifing Date: October 22, 2001

•

Carvedilol effective in heart failure patients with concomitant atrial fibrillation Source: Reuters Industry Breifing Date: September 28, 2001

•

Pacemaker for atrial fibrillation holds promise Source: Reuters Industry Breifing Date: September 04, 2001

•

New guidelines stress individualized therapies for atrial fibrillation Source: Reuters Industry Breifing Date: August 30, 2001

•

New guidelines for management of atrial fibrillation announced Source: Reuters Medical News Date: August 29, 2001 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

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Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “atrial fibrillation” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “atrial fibrillation” (or synonyms). If you know the name of a company that is relevant to atrial fibrillation, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “atrial fibrillation” (or synonyms).

Academic Periodicals covering Atrial Fibrillation Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to atrial fibrillation. In addition to these sources, you can search for articles covering atrial fibrillation that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for atrial fibrillation. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with atrial fibrillation. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).


The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to atrial fibrillation: Amiodarone •

Systemic - U.S. Brands: Cordarone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202029.html

Anticoagulants •

Systemic - U.S. Brands: Coumadin; Miradon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202050.html

Caffeine •

Systemic - U.S. Brands: Cafcit; Caffedrine Caplets; Dexitac Stay Alert Stimulant; Enerjets; Keep Alert; Maximum Strength SnapBack Stimulant Powders; NoDoz Maximum Strength Caplets; Pep-Back; Quick Pep; Ultra Pep-Back; Vivarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html

Disopyramide •

Systemic - U.S. Brands: Norpace http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202204.html

Dofetilide •

Systemic - U.S. Brands: Tikosyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500068.html

Heparin •

Systemic - U.S. Brands: Calciparine; Liquaemin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202280.html

Nicotine •

Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202280.html

•

Systemic - U.S. Brands: Habitrol; Nicorette; Nicotrol; Prostep http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202407.html

Procainamide •

Systemic - U.S. Brands: Promine; Pronestyl; Pronestyl-SR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202483.html

Propafenone •

Systemic - U.S. Brands: Rythmol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202486.html

Quinidine •

Systemic - U.S. Brands: Cardioquin; Quin-Release http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202498.html

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.


•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.


•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “atrial fibrillation” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “atrial fibrillation” (or synonyms) into the “For these words:” box. The following is a sample result: •

Stroke and Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 449-456. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail: [email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on stroke and diabetes is from a compilation and assessment of data on diabetes and its complications in the United States. Diabetes is more common in the African American population than in the white population in the United States and contributes to the increased risk of stroke among African Americans. Persons with diabetes may have a worse prognosis after a stroke. Elevated blood pressure is the major risk factor for stroke. Other risk factors for stroke, besides diabetes, include cigarette smoking and a high level of low density lipoprotein (LDL) cholesterol. Stroke is substantially increased in individuals who have other vascular diseases, especially coronary heart disease, left ventricular hypertrophy, atrial fibrillation, and peripheral vascular disease. The author maintains that preventing stroke in people with diabetes is feasible through identifying and treating risk factors, especially hypertension, cigarette smoking, and high LDL cholesterol. It is unknown whether reduction of blood glucose levels by either pharmacologic or nonpharmacologic methods will reduce the risk of stroke. It is also possible to identify individuals with atherosclerosis and to more aggressively intervene to reduce the risk of stroke by a combination of therapies. 6 figures. 6 tables. 32 references. (AA-M).

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The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “atrial fibrillation” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 18587 112 737 29 6 19471

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “atrial fibrillation” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are 15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.


used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Atrial Fibrillation In the following section, we will discuss databases and references which relate to the Genome Project and atrial fibrillation. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “atrial fibrillation” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for atrial fibrillation: 21

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

Physician Resources

•

217

Panic Disorder Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?167870 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell


anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “atrial fibrillation” (or synonyms) into the search box and click “Go.”

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Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “atrial fibrillation” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on atrial fibrillation can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to atrial fibrillation. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to atrial fibrillation. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “atrial fibrillation”:


•

Other guides Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Heart Valve Diseases http://www.nlm.nih.gov/medlineplus/heartvalvediseases.html Pacemakers and Implantable Defibrillators http://www.nlm.nih.gov/medlineplus/pacemakersandimplantabledefibrillators.ht l

Within the health topic page dedicated to atrial fibrillation, the following was listed: •

General/Overviews Arrhythmias http://www.nlm.nih.gov/medlineplus/tutorials/arrhythmiasloader.html Cardiac Arrhythmias Source: American College of Cardiology http://www.acc.org/media/patient/chd/cardiac%255Farrhythmias.htm What Are Arrhythmias? Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=560

•

Diagnosis/Symptoms Diagnosing Arrhythmias Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3 Echocardiogram Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/echocardiogram.pdf Fainting (Syncope) Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/fainting/index.html Other Symptoms of Heart Rhythm Disorders Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/other.html Rapid Heartbeat (Tachycardia and Fibrillation) Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/too_fast.html

Patient Resources

Slow Heartbeat (Bradycardia) Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/signs_symptoms/too_slow.html Transesophageal Echocardiogram (TEE) Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/tee.pdf •

Treatment Ablation Source: North American Society of Pacing and Electrophysiology http://www.naspe.org/library/patient_education/treatments/ablation/ Arrthythmia Medications Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=18 Cardioversion http://circ.ahajournals.org/cgi/reprint/106/22/e176.pdf Catheter Ablation of Arrhythmias http://circ.ahajournals.org/cgi/reprint/106/25/e203.pdf Defibrillation Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=30 Lead Extraction Source: North American Society of Pacing and Electrophysiology http://www.naspe.org/library/patient_education/treatments/lead_extraction/

•

Nutrition Caffeine, Diet and Heart Arrhythmias Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/substances/diet.html New Guidelines Focus on Fish, Fish Oil, Omega-3 Fatty Acids Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3006624

•

Specific Conditions/Aspects Arrhythmias Originating in the Atria Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=10 Arrhythmias Originating in the Ventricles Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=11 Atrial Fibrillation http://www.nlm.nih.gov/medlineplus/tutorials/atrialfibrillationloader.html

223


Atrial Fibrillation Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00291 Bundle Branch Block Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=990 Heart Block Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=992 JAMA Patient Page: Atrial Fibrillation Source: American Medical Association http://www.medem.com/search/article_display.cfm?path=%5C%5CTANQUERA Y%5CM_ContentItem&mstr=/M_ContentItem/ZZZIX1IGUJD.html&soc=JAMA/A rchives&srch_typ=NAV_SERCH Postural Tachycardia Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/postural_tachycardia_s yndrome.htm Sick Sinus Syndrome http://circ.ahajournals.org/cgi/reprint/108/20/e143.pdf Substances That Can Cause Heart Rhythm Disorders Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/substances/index.html Sudden Cardiac Death Source: Congenital Heart Information Network http://www.tchin.org/resource_room/c_art_21_.htm Wolff-Parkinson-White Syndrome Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4785 •

Children Checklist for Parents of Children with Arrhythmias Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=20 Children and Arrhythmia Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=2 Diagnosing Arrhythmias in Children Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4 Treating Arrhythmias in Children Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=26

Patient Resources

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Types of Arrhythmia in Children Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=7 •

From the National Institutes of Healt Facts about Arrhythmias/Rhythm Disorders Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/heart/other/arrhyth.htm

•

Latest News Cardiac Imaging Can Be 'Gatekeeper' for Implantable Heart-Shocker Source: 10/07/2003, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3015775 Radio Wave Surgery Can Prevent Heart Problem Source: 11/05/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14542 .html Sept. 11 Attacks Cause Rise in Heart Attack Source: 11/12/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14688 .html Weight Loss Supplement May Raise Heart Risk Source: 11/10/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14596 .html

•

Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ North American Society of Pacing and Electrophysiology http://www.naspe.org/

•

Prevention/Screening Am I at Risk? Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=562 Risk Factors & Prevention Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/risk_factors/index.html


•

Research Atrial Fibrillation Hospitalizations Triple Since 1985, Will Continue Climb Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3014151 Cardiac Imaging Can Be 'Gatekeeper' for Implantable Heart-Shocker Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3015775 Fish Oils in Heart Cells Can Block Dangerous Heart Rhythms Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3012101 Keen ER Identification Could Avert Future Strokes Source: American Heart Association http://www.americanheart.org/presenter.jhtml%3Bjsessionid=1VNULWCFBVA2R WFZOAHCCZQ?identifier=3006242 Lifesaving Properties of Beta Blockers Extend to More Patients Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3006098 Radiofrequency Treatment of Abnormal Heart Rhythm Can Damage the Vessels That Return Blood from the Lungs to the Heart Source: American College of Physicians http://www.annals.org/cgi/content/full/138/8/I-41 Study Findings Suggest Revised Approach to Therapy for Atrial Fibrillation Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/dec2002/nhlbi-04.htm Tissue-Engineered Cells Transmit Electrical Signals in Animal Hearts Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3006669

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “atrial fibrillation” (or synonyms). The following was recently posted:

Patient Resources

•

227

ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guide Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 October; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2968&nbr=2194&a mp;string=atrial+AND+fibrillation

•

Antithrombotic therapy in atrial fibrillation. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2726&nbr=1952&a mp;string=atrial+AND+fibrillation

•

Atrial fibrillation: drug treatment and electric cardioversion Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2002 March 4); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3377&nbr=2603&a mp;string=atrial+AND+fibrillation

•

Preventive health care, 2000 update. Use of ambulatory electrocardiography for the detection of paroxysmal atrial fibrillation in patients with stroke Source: Canadian Task Force on Preventive Health Care - National Government Agency [Non-U.S.]; 2000; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2703&nbr=1929&a mp;string=atrial+AND+fibrillation Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Management of New Onset Atrial Fibrillation Summary: Atrial fibrillation (AF) is the most common arrhythmia physicians face in clinical practice, accounting for about one-third of hospitalizations for arrhythmia. The prevalence of AF is 0. Source: Agency for Healthcare Research and Quality http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6996


The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to atrial fibrillation. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to atrial fibrillation. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with atrial fibrillation. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about atrial fibrillation. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at

Patient Resources

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http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “atrial fibrillation” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “atrial fibrillation”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “atrial fibrillation” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “atrial fibrillation” (or a synonym) into the search box, and click “Submit Query.”

231

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.


libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/


•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/


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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on atrial fibrillation: •

Basic Guidelines for Atrial Fibrillation Atrial fibrillation/flutter Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000184.htm MS Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000737.htm Myocarditis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000149.htm WPW Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000151.htm

•

Signs & Symptoms for Atrial Fibrillation Arrhythmia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm


Breathing difficulty, lying down Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003076.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Dyspnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Hypotension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Irregular pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Lightheadedness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Palpitations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Syncope Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Tachycardia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm •

Diagnostics and Tests for Atrial Fibrillation AMP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003368.htm Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Coronary angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003876.htm

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ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Echocardiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Exercise treadmill ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003878.htm Heart rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm Pulmonary angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003813.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm T4 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003517.htm Thyroid function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003444.htm TSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Background Topics for Atrial Fibrillation Alcohol use Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001944.htm Auscultation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002226.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Emboli Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Heart disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000147.htm


Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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ATRIAL FIBRILLATION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Propanol: An isomer of 1-propanol. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acoustic: Having to do with sound or hearing. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH]


Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aeroembolism: Joint pains, respiratory distress, and central nervous system symptoms which may follow decompression after exposure to air or other gas mixture at a pressure greater than the normal atmospheric pressure. [NIH] Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Distribution: The frequency of different ages or age groups in a given population. The distribution may refer to either how many or what proportion of the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha

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particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternans: Ipsilateral abducens palsy and facial paralysis and contralateral hemiplegia of the limbs, due to a nuclear or infranuclear lesion in the pons. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation,


especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign

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substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiplasmin: A member of the serpin superfamily found in human plasma that inhibits the lysis of fibrin clots which are induced by plasminogen activator. It is a glycoprotein, molecular weight approximately 70,000 that migrates in the alpha 2 region in immunoelectrophoresis. It is the principal plasmin inactivator in blood, rapidly forming a very stable complex with plasmin. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH]


Arrhythmogenic: Producing or promoting arrhythmia. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arthrosis: A disease of a joint. [EU] Articular: Of or pertaining to a joint. [EU] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Asynchronous: Pacing mode where only one timing interval exists, that between the stimuli. While the duration of this interval may be varied, it is not modified by any sensed event once set. As no sensing occurs, the upper and lower rate intervals are the same as the pacema. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]

Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the

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hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Bends: The form of aeroembolism that is marked by intense pain in muscles and joints due to formation of gas bubbles in the tissues. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Factors: Compounds made by living organisms that contribute to or influence a


phenomenon or process. They have biological or physiological activities. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomedical Engineering: Application of principles and practices of engineering science to biomedical research and health care. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bisoprolol: A cardioselective beta-1-adrenergic blocker. It is effective in the management of hypertension and angina pectoris. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the

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bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channel Agonists: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in vascular smooth muscle and/or cardiac muscle cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissueselective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture. [NIH]

Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the


brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Glycosides: Substances obtained from species of Digitalis, Strophanthus, and other plants that contain specific steroid glycosides or their semisynthetic derivatives and used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the Na(+)-K(+)-exchanging ATPase and they are often used in cell biological studies for that purpose. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiological: Relating to the study of the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiomyopathy, Hypertrophic: A myocardial disease characterized by hypertrophy, involving mainly the interventricular septum, interfering with left ventricular emptying. [NIH]

Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which

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can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH] Carotid Sinus: The dilated portion of the common carotid artery at its bifurcation into external and internal carotids. It contains baroreceptors which, when stimulated, cause slowing of the heart, vasodilatation, and a fall in blood pressure. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DCshock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and


leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Venous Pressure: The blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Angiography: Radiography of the vascular system of the brain after injection of a contrast medium. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical Plexus: A network of nerve fibers originating in the upper four cervical spinal cord segments. The cervical plexus distributes cutaneous nerves to parts of the neck, shoulders, and back of the head, and motor fibers to muscles of the cervical spinal column, infrahyoid muscles, and the diaphragm. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaos: Complex behavior that seems random but actually has some hidden order. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] CHD: Coronary heart disease. A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH]

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Chemotherapy: Treatment with anticancer drugs. [NIH] Chest cavity: Space in body surrounding the lungs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH]


Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray

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machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]

Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH]


Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [NIH] Cost-Benefit Analysis: A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. Cost effectiveness compares alternative ways to achieve a specific set of results. [NIH] Coumarin: A fluorescent dye. [NIH] Criterion: A standard by which something may be judged. [EU] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and

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citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Defibrillation: The act to arrest the fibrillation of (heart muscle) by applying electric shock across the chest, thus depolarizing the heart cells and allowing normal rhythm to return. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU]


Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dilatation: The act of dilating. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given

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stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. [NIH] Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastomers: A generic term for all substances having the properties of natural, reclaimed, vulcanized, or synthetic rubber, in that they stretch under tension, have a high tensile strength, retract rapidly, and recover their original dimensions fully. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocardiograph: Apparatus which, by means of currents produced by contractions of the cardiac muscle, records heart movements as electro-cardiograms. [NIH] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [NIH]

Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding


ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromagnetic Fields: Fields representing the joint interplay of electric and magnetic forces. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH]

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Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Fistula: Abnormal passage communicating with the esophagus. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Evaluation Studies: Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, clinical


trials, drug evaluation, and drug evaluation, preclinical are available. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expressed Sequence Tags: Sequence tags derived from cDNAs. Expressed sequence tags (ESTs) are partial DNA sequences from clones. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [NIH] Family Planning: Programs or services designed to assist the family in controlling

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reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fendiline: Coronary vasodilator; inhibits calcium function in muscle cells in excitationcontraction coupling; proposed as antiarrhythmic and antianginal agents. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flank Pain: Pain emanating from below the ribs and above the ilium. [NIH] Flatus: Gas passed through the rectum. [NIH] Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [NIH]


Flunarizine: Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy. [NIH] Fluoroscopy: Production of an image when X-rays strike a fluorescent screen. [NIH] Flutter: A rapid vibration or pulsation. [EU] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractals: Patterns (real or mathematical) which look similar at different scales, for example the network of airways in the lung which shows similar branching patterns at progressively higher magnifications. Natural fractals are self-similar across a finite range of scales while mathematical fractals are the same across an infinite range. Many natural, including biological, structures are fractal (or fractal-like). Fractals are related to "chaos" (see nonlinear dynamics) in that chaotic processes can produce fractal structures in nature, and appropriate representations of chaotic processes usually reveal self-similarity over time. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallopamil: Coronary vasodilator that is an analog of iproveratril (verapamil) with one more methoxy group on the benzene ring. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrula: The embryo in the early stage following the blastula, characterized by morphogenetic cell movements, cell differentiation, and the formation of the three germ

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layers. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genitourinary system: The parts of the body that play a role in reproduction, getting rid of waste products in the form of urine, or both. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less


than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Group Practice: Any group of three or more full-time physicians organized in a legally recognized entity for the provision of health care services, sharing space, equipment, personnel and records for both patient care and business management, and who have a predetermined arrangement for the distribution of income. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest

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as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH]


Hydra: A genus of freshwater cnidarians, of interest because of their complex organization and because their adult organization corresponds roughly to the gastrula of higher animals. [NIH]

Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hyperaldosteronism: Aldosteronism. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH]

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Idiopathic: Describes a disease of unknown cause. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantable pump: A small device installed under the skin to administer a steady dose of drugs. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]


Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the

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large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU]


Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU]

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Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and


diseases. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Angiography: Non-invasive method of vascular imaging and determination of internal anatomy without injection of contrast media or radiation exposure. The technique is used especially in cerebral angiography as well as for studies of other vascular structures. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] McMaster: Index used to measure painful syndromes linked to arthrosis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage. [NIH]

MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer -

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medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mibefradil: A benzimidazoyl-substituted tetraline that binds selectively to and inhibits calcium channels, T-type. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]


Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] Myocardial Contraction: Contractile activity of the heart. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle

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known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [NIH]


Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [NIH] Nisoldipine: 1,4-Dihydro-2,6-dimethyl-4 (2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-methylpropyl ester. Nisoldipine is a dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina. [NIH] Nitrendipine: Ethyl methyl 2,4-dihydro-2,6-dimethyl-4(3-nitrophenyl)-3,5pyridinedicarboxylate. A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonlinear Dynamics: The study of systems which respond disproportionately (nonlinearly) to initial conditions or perturbing stimuli. Nonlinear systems may exhibit "chaos" which is classically characterized as sensitive dependence on initial conditions. Chaotic systems, while distinguished from more ordered periodic systems, are not random. When their behavior over time is appropriately displayed (in "phase space"), constraints are evident which are described by "strange attractors". Phase space representations of chaotic systems, or strange attractors, usually reveal fractal (fractals) self-similarity across time scales. Natural, including biological, systems often display nonlinear dynamics and chaos. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides

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form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pacer: Device that delivers battery-supplied electrical stimuli over leads with electrodes in contact with the heart. Virtually all leads are inserted transvenously. Electronic circuitry regulates the timing and characteristics of the stimuli. [NIH] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]

Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpitation: A subjective sensation of an unduly rapid or irregular heart beat. [EU]


Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Admission: The process of accepting patients. The concept includes patients accepted for medical and nursing care in a hospital or other health care institution. [NIH] Patient Participation: Patient involvement in the decision-making process in matters pertaining to health. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH]

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PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phallic: Pertaining to the phallus, or penis. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacology, Clinical: The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans. [NIH] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Phrenic Nerve: The motor nerve of the diaphragm. The phrenic nerve fibers originate in the cervical spinal column (mostly C4) and travel through the cervical plexus to the diaphragm. [NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their


cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same

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population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Population Control: Includes mechanisms or programs which control the numbers of individuals in a population of humans or animals. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the


treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prone Position: The posture of an individual lying face down. [NIH] Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH]

Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some

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cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH]


Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Veins: The veins that return the oxygenated blood from the lungs to the left atrium of the heart. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH]

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Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH]


Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH]

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Responsive pacemaker: Any pacemaker that varies its rate in response to changes in the activity of a biological parameter that varies in parallel with the need for greater cardiac output, thus providing heart rate adaptability. [NIH] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Restrictive cardiomyopathy: Heart muscle disease in which the muscle walls become stiff and lose their flexibility. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhythmicity: Regular periodicity. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH]


Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Sarcoid: A cutaneus lesion occurring as a manifestation of sarcoidosis. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH]

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Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Sick Sinus Syndrome: Dysfunction of the sinoatrial node manifested by persistent sinus bradycardia, sinus arrest, sinoatrial exit block, chronic atrial fibrillation and inability of the heart to resume sinus rhythm following cardioversion for atrial fibrillation. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by


a physician, or subjective when perceived by the patient. [NIH] Sinoatrial Node: The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava and right atrium. Contraction impulses probably start in this node, spread over the atrium and are then transmitted by the atrioventricular bundle to the ventricle. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sotalol: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH]

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Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]


Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfamoyl: AMPA/Kainate antagonist. [NIH] Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Surgical Instruments: Hand-held tools or implements used by health professionals for the performance of surgical tasks. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and

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contraction. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Systemic: Affecting the entire body. [NIH] Systole: Period of contraction of the heart, especially of the ventricles. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachyarrhythmia: Tachycardia associated with an irregularity in the normal heart rhythm. [EU]

Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachycardia, Supraventricular: A generic expression for any tachycardia that originates above the bundle of His. [NIH] Tachycardia, Ventricular: An abnormally rapid ventricular rhythm with wide QRS complexes, usually in excess of 150 per minute. It is generated within the ventricle, below the Bundle of His, and is most commonly associated with atrioventricular dissociation. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Thoracotomy: Surgical incision into the chest wall. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH]


Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH]

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Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tungsten: A metallic element with the atomic symbol W, atomic number 74, and atomic weight 183.85. It is used in many manufacturing applications, including increasing the hardness, toughness, and tensile strength of steel; manufacture of filaments for incandescent light bulbs; and in contact points for automotive and electrical apparatus. [NIH] Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH]


Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and

Dictionary 299

treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]


301

INDEX 2 2-Propanol, 181, 241 A Abdomen, 148, 241, 249, 253, 273, 293, 295, 297 Abducens, 241, 243 Aberrant, 47, 135, 171, 190, 241 Ablate, 15, 41, 47, 53, 152, 189, 190, 241, 251, 260 Abscess, 241, 291 Acetone, 241 Acetylcholine, 9, 241, 278 Acidosis, 168, 241 Acoustic, 195, 241 Action Potentials, 25, 33, 176, 241 Adaptability, 241, 251, 289 Adenosine, 241, 243, 281 Adjuvant, 105, 112, 116, 123, 241, 264, 265 Adrenal Cortex, 241, 242, 288 Adrenal Medulla, 241, 251, 261, 278 Adrenergic, 16, 35, 37, 42, 56, 181, 241, 242, 246, 248, 261, 284, 286, 292, 294 Adrenergic Agonists, 16, 241 Adrenergic Antagonists, 181, 242 Adverse Effect, 34, 40, 144, 159, 242, 259, 291 Aeroembolism, 242, 247 Aetiology, 195, 242 Affinity, 242, 272, 292 Agar, 242, 282 Age Distribution, 164, 242 Age Groups, 30, 242 Aged, 80 and Over, 242 Agonist, 8, 185, 242, 294 Airway, 242, 249, 292 Aldosterone, 182, 242 Algorithms, 5, 31, 39, 160, 174, 242, 248 Alimentary, 242, 270, 271 Alkaline, 241, 242, 249 Alkaloid, 242, 286, 289 Alpha Particles, 242, 286 Alternans, 11, 182, 243 Alternative medicine, 203, 243 Amino Acid Sequence, 243, 244, 262, 265 Amino Acids, 42, 243, 244, 265, 280, 283, 285, 291

Amiodarone, 33, 52, 53, 64, 65, 74, 76, 77, 80, 103, 109, 110, 141, 142, 156, 184, 201, 206, 243 Amlodipine, 151, 243 Ampulla, 243, 260 Amyloid, 140, 243 Anabolic, 100, 107, 243 Anabolic Steroids, 100, 107, 243 Anaesthesia, 94, 243, 269 Anal, 243, 263, 273 Analog, 243, 264, 271 Analogous, 28, 31, 243, 296 Anatomical, 5, 8, 22, 39, 48, 66, 243, 246, 255, 269, 280, 290 Anemia, 243, 266 Anesthesia, 5, 6, 148, 242, 243, 244, 246, 260 Anesthetics, 243, 261 Aneurysm, 71, 244, 298 Angina, 11, 150, 151, 161, 163, 181, 243, 244, 248, 271, 277, 278, 284 Angina Pectoris, 151, 161, 181, 243, 244, 248, 271, 284 Anginal, 244, 278 Angiography, 238, 239, 244 Angioplasty, 30, 149, 174, 244, 246 Angiotensin-Converting Enzyme Inhibitors, 36, 244 Angiotensinogen, 182, 244, 288 Animal model, 37, 40, 42, 45, 47, 163, 244 Anode, 148, 244 Antagonism, 244, 258 Anterior Cerebral Artery, 244, 252 Antianginal, 243, 244, 263 Antibacterial, 244, 293 Antibiotic, 3, 30, 244, 293 Antibiotic Prophylaxis, 3, 244 Antibodies, 244, 245, 267, 269, 273 Antibody, 28, 242, 244, 245, 254, 267, 269, 274, 286, 293 Anticoagulant, 36, 38, 53, 80, 100, 106, 127, 245, 285, 299 Antigen, 242, 244, 245, 254, 267, 268, 269, 274, 286 Antihypertensive, 245, 277, 278 Anti-inflammatory, 40, 245, 246 Anti-Inflammatory Agents, 245, 246 Antimicrobial, 140, 245


Antineoplastic, 245, 274, 277, 297 Antineoplastic Agents, 245, 277 Antioxidant, 33, 245, 279 Antiplasmin, 104, 111, 245 Antiseptic, 241, 245 Antithrombotic, 32, 50, 66, 100, 101, 105, 106, 107, 111, 112, 227, 245 Anxiety, 4, 18, 25, 145, 159, 181, 245, 284 Aorta, 154, 245, 250, 256, 266, 298 Apnea, 14, 245 Apolipoproteins, 245, 272 Applicability, 41, 245 Aqueous, 245, 247, 256, 260 Arginine, 245, 278 Aromatic, 245, 294 Arrhythmogenic, 16, 29, 70, 121, 191, 246 Arterial, 7, 13, 19, 31, 35, 51, 57, 163, 181, 246, 252, 253, 268, 278, 285, 295, 296 Arteries, 134, 168, 188, 245, 246, 248, 252, 255, 256, 266, 271, 273, 275, 276, 286 Arteriolar, 246, 249, 263, 288 Arterioles, 246, 248, 250, 276, 298 Arthrosis, 246, 274 Articular, 40, 246, 272 Artifacts, 182, 246 Aspirin, 7, 21, 32, 51, 58, 65, 85, 116, 129, 201, 246 Asymptomatic, 23, 69, 100, 107, 246, 263 Asynchronous, 144, 246 Atenolol, 34, 246 Atherectomy, 246, 260 Atrioventricular Node, 17, 90, 138, 144, 178, 179, 191, 246, 294 Auricular, 120, 246 Autonomic, 11, 44, 55, 60, 88, 122, 241, 246, 278, 292, 294 Autonomic Nervous System, 88, 246, 292, 294 B Bacteria, 244, 245, 247, 260, 261, 275, 287, 293, 296, 297 Bacteriophage, 247, 282, 296 Bacteriuria, 247, 297 Base, 44, 165, 247, 257, 265, 271, 295 Basement Membrane, 247, 262 Bends, 189, 247 Benign, 155, 247 Benzene, 247, 264 Beta blocker, 65, 247 Beta-pleated, 243, 247 Beta-Thromboglobulin, 104, 111, 247 Bilateral, 57, 80, 247

Bile, 247, 264, 267, 273, 293 Bioavailability, 142, 247 Biochemical, 33, 43, 47, 49, 247, 291 Biological Factors, 17, 247 Biological response modifier, 248, 270 Biomedical Engineering, 4, 15, 156, 248 Biopsy, 248, 280 Biosynthesis, 248, 291 Biotechnology, 12, 49, 51, 195, 203, 213, 248 Biphasic, 57, 60, 137, 201, 248 Bisoprolol, 180, 181, 248 Blood Cell Count, 248, 266 Blood Coagulation, 248, 249, 295 Blood Glucose, 196, 214, 248, 270 Blood vessel, 127, 149, 175, 244, 247, 248, 249, 250, 251, 252, 253, 255, 260, 261, 265, 271, 273, 280, 281, 292, 293, 296, 297, 298 Blood Volume, 248, 250 Body Fluids, 248, 249, 292 Bolus, 143, 144, 248 Bolus infusion, 248 Bone Marrow, 247, 248, 269, 273, 275, 276 Bone scan, 248, 290 Bowel, 243, 249, 258 Bowel Movement, 249, 258 Brachiocephalic Veins, 249, 294 Bradycardia, 139, 140, 223, 249, 291 Bradykinin, 249, 278, 282 Branch, 224, 235, 249, 260, 273, 280, 281, 285, 292, 295 Breakdown, 185, 249, 258, 264 Bronchi, 249, 261, 271, 296 Bronchodilator, 249, 271 Bypass, 42, 75, 134, 249 C Calcium Channel Agonists, 16, 249 Calcium channel blocker, 151, 243, 249, 278, 298 Calcium Channel Blockers, 249, 278 Calcium Channels, 30, 75, 249, 275 Calmodulin, 42, 249, 264 Capillary, 249, 250, 265, 298 Carbohydrates, 250, 252 Carbon Dioxide, 250, 263, 264, 288, 298 Carcinogen, 250, 275, 297 Carcinogenic, 247, 250, 270, 284, 293 Cardiac arrest, 6, 7, 250, 294 Cardiac Glycosides, 9, 250 Cardiac Output, 121, 138, 150, 154, 156, 157, 161, 174, 176, 191, 250, 289, 294

Index 303

Cardiological, 59, 250 Cardiomyopathy, 18, 78, 90, 139, 140, 142, 184, 250 Cardiomyopathy, Hypertrophic, 139, 140, 250 Cardiopulmonary, 134, 138, 158, 169, 170, 250 Cardiopulmonary Bypass, 134, 158, 169, 170, 250 Cardioselective, 246, 248, 250, 284 Cardiotonic, 250, 258 Cardiotoxicity, 40, 250 Cardiovascular Agents, 106, 250 Cardiovascular disease, 36, 38, 46, 138, 250 Cardiovascular System, 181, 182, 251 Cardioversion, 31, 47, 57, 60, 61, 63, 64, 65, 66, 68, 71, 73, 74, 76, 78, 80, 85, 88, 90, 92, 93, 94, 95, 96, 97, 102, 103, 105, 106, 109, 110, 111, 112, 115, 119, 123, 125, 128, 135, 137, 141, 142, 143, 144, 145, 150, 160, 163, 173, 176, 190, 200, 201, 202, 223, 227, 251, 291 Carotid Sinus, 117, 118, 122, 251 Case report, 104, 116, 121, 251, 253 Case series, 52, 251, 253 Catecholamine, 251, 281 Catheter Ablation, 8, 11, 22, 29, 43, 52, 75, 78, 83, 88, 90, 93, 116, 188, 223, 251 Catheterization, 244, 251 Catheters, 22, 29, 134, 189, 251 Cathode, 148, 244, 251, 260 Caudal, 251, 268, 283 Causal, 18, 19, 251 Cell Adhesion, 40, 251 Cell Adhesion Molecules, 40, 251 Cell Death, 251, 252, 277 Cell Differentiation, 251, 264, 291 Cell Division, 247, 252, 275, 282, 290 Cell membrane, 25, 249, 252, 257, 264, 281, 283, 299 Cell Physiology, 8, 252 Cell proliferation, 149, 252, 291 Central Nervous System, 144, 241, 242, 246, 247, 249, 252, 264, 277, 283, 291 Central Venous Pressure, 35, 252 Centrifugation, 252, 266 Cerebral, 20, 60, 72, 73, 100, 161, 244, 252, 257, 261, 262, 264, 266, 274, 285, 295, 296 Cerebral Angiography, 252, 274 Cerebral Infarction, 20, 252

Cerebrovascular, 19, 80, 82, 249, 251, 252, 278 Cerebrum, 252 Cervical, 45, 252, 266, 281 Cervical Plexus, 252, 281 Cervix, 252 Chaos, 252, 264, 278 Character, 244, 252 CHD, 36, 222, 252, 256, 273 Chemotherapy, 116, 253 Chest cavity, 148, 253 Chest Pain, 23, 140, 253 Chest wall, 253, 295 Cholesterol, 36, 38, 46, 196, 214, 247, 252, 253, 256, 272, 273, 290, 293 Cholesterol Esters, 253, 272 Chromosomal, 27, 43, 253 Chromosome, 79, 253, 272, 290 Chronic renal, 253, 264 Chronotropic, 33, 253 Chylomicrons, 253, 272 Circulatory system, 139, 191, 253 Clamp, 14, 27, 54, 253 Clinical Medicine, 31, 89, 253, 283 Clinical study, 253, 255 Cloning, 19, 20, 28, 248, 253 Coagulation, 7, 19, 120, 185, 189, 248, 253, 282, 296, 299 Cofactor, 253, 285, 295 Collapse, 249, 254, 292 Combination Therapy, 116, 254, 261 Complement, 254, 265, 274, 282 Complementary and alternative medicine, 115, 124, 254 Complementary medicine, 115, 254 Computational Biology, 213, 254 Computed tomography, 254, 255, 290 Computer Simulation, 25, 254 Computerized axial tomography, 254, 290 Concomitant, 61, 153, 202, 255 Confounding, 18, 46, 255 Congestion, 140, 255 Connective Tissue, 248, 255, 263, 264, 265, 273, 289 Connexins, 255, 264 Consciousness, 23, 150, 172, 176, 255, 257, 258, 295 Constriction, 255, 271, 298 Constriction, Pathologic, 255, 298 Contamination, 136, 255 Continuous infusion, 56, 255 Contractility, 42, 137, 164, 244, 255


Contraindications, ii, 156, 255 Contralateral, 243, 255 Contrast Media, 255, 274 Control group, 36, 255, 284, 287 Controlled clinical trial, 21, 36, 255, 287 Controlled study, 128, 129, 255 Coordination, 138, 255 Coronary Arteriosclerosis, 255, 276 Coronary Artery Bypass, 6, 35, 47, 53, 54, 58, 65, 68, 76, 84, 103, 109, 122, 256 Coronary Circulation, 244, 256 Coronary Disease, 46, 92, 100, 107, 256 Coronary heart disease, 18, 36, 196, 214, 250, 252, 256 Coronary Thrombosis, 256, 275, 276 Coronary Vessels, 256 Cortical, 256, 262, 290 Cost-benefit, 32, 256 Cost-Benefit Analysis, 32, 256 Coumarin, 51, 256 Criterion, 137, 256 Critical Care, 19, 74, 256 Curative, 8, 67, 163, 201, 256, 295 Cyclic, 250, 256, 266, 278, 284 Cytokine, 40, 256 Cytoplasm, 252, 256, 266, 276, 290 Cytotoxic, 171, 256, 291 D Dairy Products, 256, 290 Data Collection, 13, 18, 256, 264 Databases, Bibliographic, 213, 256 Deletion, 44, 257 Delirium, 6, 257 Dementia, 24, 257 Density, 15, 24, 38, 43, 137, 168, 196, 214, 252, 257, 272, 279, 292 Dental Care, 3, 257 Depolarization, 9, 26, 146, 152, 153, 166, 174, 175, 188, 190, 191, 257, 291 Deuterium, 257, 268 Diabetes Mellitus, 29, 36, 257, 266 Diabetic Retinopathy, 151, 181, 257, 281 Diagnostic procedure, 133, 203, 257 Dialyzer, 257, 267 Diaphragm, 252, 257, 281 Diastole, 160, 257 Diastolic, 6, 9, 13, 138, 160, 257, 268 Digestion, 242, 247, 249, 258, 273, 293 Digestive system, 131, 258 Digitalis, 10, 77, 106, 118, 121, 145, 250, 258

Dilatation, 8, 16, 20, 38, 63, 244, 258, 284, 298 Dilated cardiomyopathy, 20, 56, 140, 258 Dilation, 140, 246, 249, 258, 298 Diltiazem, 151, 258 Dimethyl, 258, 271, 277, 278 Disease Progression, 24, 258 Disinfectant, 241, 258 Disorientation, 257, 258 Dissociation, 242, 258, 271, 295 Distal, 136, 146, 153, 156, 157, 162, 178, 251, 256, 258, 260, 285 Diuretic, 182, 258, 264 Dizziness, 23, 144, 150, 161, 162, 172, 174, 176, 238, 258, 298 Docetaxel, 116, 258 Dorsal, 258, 283 Double-blinded, 74, 258 Drive, ii, vi, 56, 99, 103, 110, 143, 258 Drug Evaluation, 259, 262 Drug Evaluation, Preclinical, 259, 262 Drug Interactions, 19, 30, 207, 259 Drug Toxicity, 168, 259 Duodenum, 247, 259, 260, 293 Dyes, 243, 259 Dyspareunia, 259, 261 Dyspnea, 140, 163, 238, 259 Dystrophy, 60, 259 E Echocardiography, 6, 14, 48, 71, 78, 91, 93, 94, 95, 106, 112, 239, 259 Ectopic, 71, 155, 163, 171, 177, 190, 191, 259 Edema, 257, 259, 264, 283 Effector, 241, 254, 259 Elastomers, 140, 259 Elective, 83, 259 Electric Conductivity, 15, 259 Electric shock, 128, 257, 259 Electrocardiogram, 14, 31, 58, 87, 151, 155, 259 Electrocardiograph, 145, 259 Electrocardiography, 49, 106, 227, 259 Electrocoagulation, 253, 259 Electrode, 15, 22, 136, 143, 148, 156, 159, 162, 166, 171, 176, 189, 190, 244, 251, 260 Electrolyte, 168, 182, 242, 257, 260, 283, 292 Electromagnetic Fields, 45, 260 Electrons, 245, 247, 251, 259, 260, 271, 279, 286

Index 305

Electrophysiological, 5, 33, 43, 44, 45, 48, 49, 66, 134, 142, 146, 170, 177, 179, 260, 298 Emboli, 14, 20, 27, 101, 108, 137, 163, 239, 260, 299 Embolism, 20, 81, 100, 161, 260, 286, 299 Embolization, 14, 101, 108, 260, 299 Embolus, 260, 269 Embryo, 251, 260, 264, 269 Emulsion, 260, 263 Encephalopathy, 6, 7, 260 Endarterectomy, 30, 244, 246, 260 Endocardium, 15, 22, 260, 297 Endoscope, 260 Endoscopic, 122, 260 Endothelial cell, 260, 295, 297 Endothelium, 102, 108, 159, 261, 278, 297 Endothelium, Lymphatic, 261 Endothelium, Vascular, 261 Endothelium-derived, 102, 108, 261, 278 Endotoxic, 261, 272 Endotoxin, 261, 297 Environmental Health, 212, 214, 261 Enzymatic, 20, 249, 254, 261, 263, 267, 289 Enzyme, 38, 182, 185, 259, 261, 266, 273, 275, 282, 285, 288, 291, 294, 295, 299 Enzyme Inhibitors, 38, 261, 282 Epidemiological, 73, 261 Epinephrine, 182, 241, 242, 261, 271, 278 Epithelium, 247, 261 Esophageal, 52, 261 Esophageal Fistula, 52, 261 Esophagus, 258, 261, 293 Estrogen, 16, 261 Estrogen Replacement Therapy, 16, 261 Ethnic Groups, 34, 261 Evaluation Studies, 5, 261 Evoke, 262, 293 Excitability, 144, 262, 286 Excitation, 24, 143, 171, 187, 190, 246, 262, 263 Excitatory, 190, 262 Exercise Test, 262 Exercise Tolerance, 35, 167, 262 Exogenous, 262, 265 Exon, 44, 262 Expressed Sequence Tags, 45, 262 Extracellular, 9, 25, 182, 243, 255, 262, 263, 292 Extracellular Matrix, 182, 255, 262, 263 Extracellular Space, 262 Extraction, 7, 67, 126, 223, 262

Extravasation, 262, 266 Extremity, 146, 252, 262 F Facial, 243, 262, 292 Facial Paralysis, 243, 262 Family Planning, 213, 262 Fat, 167, 248, 252, 256, 260, 263, 272, 289, 290, 292 Fatigue, 162, 163, 238, 263, 266 Felodipine, 151, 263 Femoral, 250, 263 Femoral Artery, 250, 263 Fendiline, 151, 263 Fibrin, 69, 245, 248, 263, 282, 295, 296 Fibrinogen, 20, 263, 282, 285, 295 Fibrinolysis, 185, 263 Fibroblasts, 263, 270 Fibrosis, 263, 290 Fixation, 179, 263 Flank Pain, 57, 263 Flatus, 263, 264 Flecainide, 85, 263 Flunarizine, 151, 264 Fluoroscopy, 149, 175, 264 Flutter, 23, 33, 35, 42, 60, 66, 67, 74, 78, 90, 91, 102, 106, 108, 112, 119, 120, 128, 129, 141, 142, 143, 146, 147, 150, 151, 154, 155, 160, 162, 164, 165, 167, 173, 181, 193, 194, 197, 198, 237, 246, 264 Focus Groups, 39, 264 Fold, 16, 33, 142, 184, 264 Forearm, 248, 264 Fovea, 263, 264 Fractals, 264, 278 Friction, 140, 264 Frontal Lobe, 244, 252, 264 Furosemide, 56, 264 G Gallbladder, 258, 264 Gallopamil, 151, 264 Ganglia, 44, 241, 264, 277, 294 Gap Junctions, 8, 25, 255, 264 Gas, 152, 159, 242, 247, 250, 263, 264, 268, 278, 294, 298 Gas exchange, 159, 264, 298 Gastrin, 264, 267 Gastrointestinal, 55, 181, 249, 261, 264, 291, 292, 293 Gastrointestinal tract, 55, 181, 264, 291, 293 Gastrula, 264, 268 Gelatin, 265, 266, 295


Gene, 10, 12, 17, 19, 20, 27, 28, 34, 42, 44, 45, 49, 172, 195, 200, 248, 255, 265, 290 Gene Expression, 10, 12, 44, 45, 265 Gene Targeting, 43, 265 Generator, 145, 148, 159, 166, 172, 265 Genetic Code, 265, 278 Genetic Engineering, 248, 253, 265 Genital, 265, 297 Genitourinary, 181, 265, 297 Genitourinary system, 181, 265 Genotype, 7, 19, 163, 265, 281 Geriatric, 5, 85, 97, 100, 105, 106, 111, 112, 265 Gland, 241, 265, 273, 280, 282, 290, 293, 296 Glomerular, 151, 181, 265, 278, 288 Glomerular Filtration Rate, 265, 278 Glomeruli, 265 Glomerulonephritis, 151, 181, 265 Glomerulus, 265 Glucose, 101, 103, 108, 109, 248, 257, 265, 268, 270 Glucose Intolerance, 257, 265 Glucuronic Acid, 266, 267 Glycine, 266, 291 Glycoprotein, 245, 263, 266, 295, 297 Governing Board, 266, 283 Grade, 23, 29, 38, 266 Graft, 6, 84, 266 Grafting, 35, 53, 54, 58, 84, 122, 256, 266, 269 Granulocytes, 266, 291, 299 Group Practice, 37, 266 Growth, 19, 29, 182, 243, 244, 245, 251, 252, 266, 270, 274, 282, 296 Guanylate Cyclase, 266, 278 H Health Status, 26, 126, 266 Heart attack, 251, 266 Heart failure, 5, 10, 13, 14, 20, 24, 26, 34, 35, 36, 44, 46, 56, 60, 65, 71, 91, 92, 106, 119, 129, 137, 138, 141, 142, 150, 180, 181, 182, 183, 184, 202, 244, 250, 255, 266, 273 Heart Valves, 195, 266 Heartbeat, 138, 152, 154, 159, 161, 177, 179, 222, 223, 266, 294, 298 Hematocrit, 117, 248, 266 Hematoma, 19, 266 Hemiplegia, 243, 266 Hemodialysis, 60, 257, 267 Hemodynamics, 35, 267

Hemorrhage, 7, 19, 32, 259, 267, 293, 299 Heparin, 50, 63, 66, 94, 206, 267 Hepatic, 257, 267 Heredity, 265, 267 Heterogeneity, 18, 27, 154, 242, 267 Histamine, 264, 267 Homogeneous, 47, 154, 267 Homologous, 255, 265, 267, 290, 294 Hormonal, 138, 182, 261, 267, 280 Hormone, 36, 44, 182, 242, 261, 264, 267, 270, 289, 291, 295, 296 Hormone Replacement Therapy, 36, 267 Humoral, 40, 267 Humour, 267 Hybrid, 73, 90, 194, 267 Hybridization, 12, 267 Hybridomas, 267, 270 Hydra, 69, 268 Hydrogen, 186, 241, 247, 250, 257, 268, 272, 276, 277, 279, 281, 285 Hydrolysis, 268, 281, 283, 285 Hydrophilic, 140, 268 Hydrophobic, 268, 272 Hyperaldosteronism, 151, 268 Hyperlipidemia, 36, 268 Hyperplasia, 151, 181, 268 Hypersensitivity, 117, 268, 289 Hyperthyroidism, 18, 44, 74, 268, 284 Hypertrophic cardiomyopathy, 74, 91, 140, 150, 181, 268 Hypertrophy, 10, 14, 28, 45, 84, 196, 214, 250, 268 Hypoglycaemia, 257, 268 Hypothalamus, 247, 268, 282 Hypothyroidism, 40, 268 Hypoxia, 168, 257, 268 I Id, 113, 123, 224, 227, 228, 234, 236, 268 Idiopathic, 56, 102, 108, 269, 290 Illusion, 269, 298 Immune response, 40, 241, 245, 269, 274, 299 Immune system, 269, 273, 297, 299 Immunization, 269, 284 Immunoelectrophoresis, 242, 245, 269 Immunogenic, 269, 272, 286 Immunology, 241, 242, 269 Immunosuppressive, 40, 269 Impairment, 25, 257, 269, 275 Implantable pump, 143, 269 Implantation, 12, 26, 61, 90, 148, 156, 269 In vitro, 12, 14, 15, 24, 42, 259, 269, 296

Index 307

In vivo, 14, 15, 17, 28, 31, 33, 42, 49, 267, 269 Incision, 158, 169, 189, 269, 271, 295 Incisional, 155, 269 Indicative, 150, 177, 193, 269, 280, 298 Induction, 8, 45, 145, 269 Infant, Newborn, 242, 269 Infarction, 7, 129, 252, 269, 288 Infection, 153, 241, 247, 248, 257, 269, 273, 289, 294, 299 Infiltration, 265, 270 Inflammation, 40, 81, 245, 246, 263, 270, 289 Informed Consent, 14, 270 Infusion, 136, 270 Initiation, 8, 14, 25, 33, 90, 270 Inlay, 270, 289 Innervation, 116, 270 Inotropic, 246, 263, 270 Insight, 10, 21, 36, 41, 67, 270 Insulin, 101, 103, 108, 109, 249, 270 Insulin-dependent diabetes mellitus, 270 Interferon, 40, 270 Interferon-alpha, 270 Interleukin-4, 41, 270 Interleukin-6, 75, 92, 270 Intermittent, 146, 270, 273 Interstitial, 25, 170, 262, 270, 288 Intestines, 264, 270, 290 Intoxication, 104, 121, 257, 271, 299 Intracellular, 9, 24, 25, 28, 34, 249, 269, 271, 278, 283, 284, 291 Intravascular, 146, 271 Intravenous, 65, 76, 77, 137, 144, 270, 271 Intrinsic, 35, 45, 103, 109, 139, 155, 173, 174, 191, 242, 247, 271 Invasive, 4, 22, 29, 41, 44, 83, 90, 134, 170, 178, 182, 188, 189, 271, 274 Involuntary, 263, 271, 276 Ion Channels, 8, 33, 44, 49, 271 Ionization, 271 Ionizing, 179, 243, 271 Ions, 247, 249, 250, 258, 260, 268, 271, 283, 285, 290 Irrigation, 136, 157, 271 Ischemia, 10, 11, 140, 168, 271, 288 Ischemic stroke, 19, 20, 29, 50, 102, 108, 271 Isoproterenol, 42, 271 Isradipine, 151, 271 J Joint, 38, 40, 92, 242, 246, 260, 271

K Kb, 212, 271 Kinetic, 14, 271 L Labile, 14, 254, 272 Large Intestine, 258, 271, 272, 287, 292 Latency, 144, 272 Latent, 9, 165, 272 Length of Stay, 35, 82, 94, 272 Lethal, 20, 30, 272 Lethargy, 268, 272 Leukocytes, 248, 266, 270, 272, 276, 297 Levo, 272, 274 Library Services, 234, 272 Life cycle, 248, 272 Life Expectancy, 18, 272 Ligaments, 255, 272 Ligands, 44, 251, 272 Linkage, 20, 28, 272 Lip, 51, 69, 72, 75, 86, 102, 104, 105, 108, 109, 111, 116, 193, 194, 272 Lipid, 38, 46, 245, 270, 272, 279 Lipid A, 38, 272 Lipid Peroxidation, 272, 279 Lipophilic, 141, 184, 272 Lipopolysaccharides, 272 Lipoprotein, 196, 214, 272, 273 Lisinopril, 65, 273 Liver, 181, 247, 258, 260, 264, 266, 267, 273, 288, 290 Liver scan, 273, 290 Lobe, 244, 252, 273 Localization, 5, 24, 154, 273 Localized, 9, 17, 27, 70, 263, 266, 269, 273, 282, 290 Longitudinal Studies, 19, 273 Longitudinal study, 60, 273 Long-Term Care, 202, 273 Loop, 120, 152, 160, 162, 273 Low-density lipoprotein, 272, 273 Lumen, 136, 140, 146, 149, 157, 178, 261, 273 Lung Transplantation, 53, 273 Lymph, 252, 253, 260, 261, 267, 273, 290 Lymph node, 252, 273, 290 Lymphatic, 261, 269, 273, 293 Lymphatic system, 273, 293 Lymphocyte, 245, 273, 274 M Macula, 264, 274 Macula Lutea, 274 Macular Degeneration, 80, 274


Magnetic Resonance Angiography, 74, 274 Magnetic Resonance Imaging, 22, 29, 188, 274, 290 Major Histocompatibility Complex, 270, 274 Malignant, 49, 135, 245, 274 Mammary, 256, 274 Manifest, 44, 266, 274 McMaster, 101, 107, 274 Meat, 274, 290 Mediate, 10, 40, 49, 251, 274 Mediator, 11, 182, 274, 291 Medical Records, 7, 36, 274, 289 Medical Staff, 258, 274 Medicament, 161, 165, 274 Medication Errors, 30, 274 MEDLINE, 213, 274 Melphalan, 104, 110, 274 Membrane, 9, 10, 252, 254, 257, 258, 262, 271, 275, 281, 286, 289, 290, 291 Membrane Glycoproteins, 275 Memory, 14, 24, 136, 152, 257, 275 Meninges, 252, 275 Menopause, 275, 283, 284 Mental Disorders, 131, 275, 284, 285 Mental Health, iv, 4, 131, 212, 215, 275, 284, 285 Mental Processes, 24, 258, 275 Mentors, 19, 37, 275 Meta-Analysis, 65, 85, 196, 275 Metabolic disorder, 138, 275 Metastasis, 251, 275 MI, 14, 84, 97, 240, 275 Mibefradil, 151, 275 Microbe, 275, 296 Microorganism, 253, 275, 299 Microscopy, 9, 247, 275 Migration, 182, 275 Mitochondrial Swelling, 275, 277 Mitotic, 258, 275 Mitotic inhibitors, 258, 275 Mitral Valve, 47, 276 Modeling, 5, 47, 120, 276 Modification, 27, 103, 109, 265, 276, 286 Molecule, 245, 247, 254, 258, 259, 261, 262, 268, 276, 279, 287, 291, 298 Monitor, 54, 87, 121, 157, 160, 182, 183, 276, 278 Monocytes, 270, 272, 276 Mononuclear, 276, 297 Morphology, 11, 25, 62, 82, 154, 155, 276

Motor nerve, 276, 281 Multicenter study, 68, 276 Muscle Contraction, 276, 290 Muscle Fibers, 159, 180, 246, 276, 292 Muscular Dystrophies, 259, 276 Musculature, 39, 163, 276 Mydriatic, 258, 276 Myeloproliferative Disorders, 247, 276 Myocardial Contraction, 152, 276 Myocardial infarction, 7, 11, 14, 15, 36, 38, 48, 150, 181, 185, 247, 256, 275, 276, 284, 299 Myocardial Ischemia, 138, 244, 256, 276 Myopathy, 157, 181, 277 N Natriuresis, 182, 244, 277 NCI, 1, 130, 211, 277 Necrosis, 149, 174, 175, 252, 269, 275, 276, 277, 288, 290 Need, 3, 4, 16, 17, 34, 93, 135, 148, 151, 159, 160, 164, 181, 196, 214, 229, 253, 277, 289 Nephropathy, 151, 181, 277 Nervous System, 182, 246, 252, 266, 274, 277, 280, 294 Neural, 126, 147, 243, 267, 277, 280 Neurologic, 277, 296 Neurology, 19, 58, 85, 100, 101, 103, 104, 105, 107, 110, 111, 112, 277 Neuromuscular, 241, 262, 277 Neuromuscular Junction, 241, 277 Neuronal, 249, 277 Neurons, 262, 264, 277, 294 Neurophysiology, 257, 277 Neuropsychological Tests, 6, 277 Neutrons, 242, 277, 286 Nicardipine, 151, 277 Nifedipine, 151, 278 Nimodipine, 151, 278 Nisoldipine, 151, 278 Nitrendipine, 151, 278 Nitric Oxide, 102, 108, 278 Nitrogen, 185, 186, 242, 263, 274, 278 Nonlinear Dynamics, 39, 264, 278 Norepinephrine, 9, 182, 241, 242, 278 Nuclear, 243, 260, 277, 278 Nuclei, 242, 244, 260, 262, 265, 274, 277, 278, 285 Nucleic acid, 185, 265, 267, 278, 286 Nucleic Acid Hybridization, 267, 278 Nursing Care, 279, 280

Index 309

O Observational study, 50, 51, 62, 101, 107, 279 On-line, 5, 83, 237, 279 Opacity, 257, 279 Ophthalmology, 263, 279 Optic Disk, 257, 274, 279 Osteoporosis, 261, 279 Outpatient, 7, 21, 30, 90, 158, 279 Oxidation, 245, 272, 279 Oxidative Stress, 33, 279 Oxygen Consumption, 33, 262, 279, 288 Oxygenator, 250, 279 P Pacer, 145, 279 Pain Threshold, 47, 279 Palliative, 8, 279, 295 Palpitation, 138, 279 Palsy, 243, 280 Pancreas, 258, 270, 280 Pancreatic, 249, 280 Parenchyma, 19, 280 Particle, 280, 292, 296 Patch, 9, 49, 280 Pathogenesis, 45, 280 Pathologic, 241, 248, 255, 268, 280, 298 Pathologies, 137, 156, 280 Pathophysiology, 26, 37, 54, 138, 182, 280 Patient Admission, 158, 280 Patient Participation, 130, 280 Peptide, 12, 13, 64, 72, 78, 182, 201, 280, 283, 285, 296 Percutaneous, 94, 280 Perfusion, 140, 159, 160, 174, 268, 280 Pericardium, 178, 280 Periodicity, 39, 280, 289 Perioperative, 5, 280 Peripheral Vascular Disease, 181, 196, 214, 264, 280 PH, 33, 101, 107, 281 Phallic, 263, 281 Pharmaceutical Preparations, 164, 165, 186, 265, 281 Pharmacodynamic, 77, 281 Pharmacokinetic, 77, 281 Pharmacologic, 11, 26, 33, 102, 104, 109, 110, 120, 196, 214, 243, 281, 296 Pharmacology, Clinical, 34, 281 Pharmacotherapy, 17, 33, 62, 97, 281 Phenotype, 12, 20, 28, 44, 163, 281 Phenyl, 186, 281 Phospholipases, 281, 291

Phospholipids, 263, 272, 281 Phosphorus, 249, 281 Phosphorylated, 42, 281 Phosphorylation, 42, 281 Photocoagulation, 253, 281 Phrenic Nerve, 159, 281 Physiologic, 11, 26, 41, 43, 49, 242, 248, 281, 284, 287, 294 Physiology, 9, 18, 24, 34, 89, 117, 156, 250, 260, 277, 281 Pilot study, 32, 46, 65, 68, 282 Pituitary Gland, 182, 282 Plants, 242, 250, 258, 265, 276, 278, 282, 296 Plaque, 31, 244, 246, 282 Plasma protein, 261, 282, 285 Plasmin, 104, 111, 245, 282 Plasminogen, 245, 282 Platelet Activation, 86, 116, 282, 291 Platelet Aggregation, 278, 282 Platelets, 104, 111, 247, 278, 282, 291, 296 Platinum, 140, 273, 282 Poisoning, 257, 259, 271, 282 Polymers, 282, 285, 294 Polymorphism, 19, 20, 34, 92, 282 Polypeptide, 72, 243, 263, 267, 282, 283, 299 Pons, 243, 262, 283 Population Control, 92, 283 Port, 66, 95, 136, 283 Port-a-cath, 283 Posterior, 70, 243, 258, 280, 283 Postmenopausal, 36, 261, 279, 283 Postnatal, 283, 293 Postoperative, 5, 41, 42, 60, 73, 77, 82, 84, 92, 195, 283 Postsynaptic, 283, 291 Postural, 224, 283 Potassium, 17, 30, 73, 87, 101, 103, 108, 109, 142, 164, 165, 200, 242, 283, 286 Potassium Channels, 17, 73, 142, 283 Potentiation, 283, 291 Practice Guidelines, 21, 36, 59, 215, 226, 227, 283 Preclinical, 30, 40, 259, 283 Precursor, 91, 182, 244, 259, 261, 278, 282, 283, 285 Pre-Eclampsia, 247, 283 Prevalence, 16, 18, 25, 26, 44, 50, 92, 105, 111, 142, 184, 227, 283 Primary endpoint, 6, 13, 26, 283 Primary Prevention, 14, 36, 75, 284


Probe, 11, 48, 134, 170, 284 Progression, 40, 47, 138, 244, 284 Progressive, 20, 140, 251, 253, 257, 261, 266, 276, 277, 282, 284, 288 Projection, 278, 284 Promoter, 44, 284 Prone, 45, 95, 159, 284 Prone Position, 95, 284 Propafenone, 87, 200, 206, 284 Prophylaxis, 32, 80, 105, 111, 164, 165, 186, 264, 284, 299 Proportional, 144, 284 Propranolol, 246, 284 Prospective study, 56, 67, 273, 284 Prostaglandin, 244, 284 Protease, 254, 285 Protein C, 37, 243, 245, 247, 272, 285 Protein Kinases, 42, 285 Protein S, 195, 248, 265, 285 Proteins, 17, 24, 28, 34, 37, 49, 185, 243, 245, 252, 254, 255, 264, 267, 269, 276, 278, 280, 282, 285, 286, 287, 291, 295, 296, 299 Proteinuria, 151, 181, 283, 285 Proteolytic, 254, 263, 282, 285 Prothrombin, 130, 285, 295 Prothrombin Time, 130, 285 Protocol, 18, 34, 47, 51, 156, 285 Protons, 242, 268, 271, 285, 286 Proximal, 136, 146, 152, 162, 189, 258, 285, 291 Psychiatry, 263, 285 Psychomotor, 257, 285 Public Health, 7, 13, 24, 101, 107, 164, 215, 285 Public Policy, 213, 285 Publishing, 49, 285 Pulmonary Artery, 248, 286, 298 Pulmonary Embolism, 286, 299 Pulmonary hypertension, 31, 151, 181, 286 Pulsation, 264, 286 Pupil, 258, 276, 286 Purines, 286, 291 Q Quality of Life, 7, 13, 23, 24, 26, 32, 35, 42, 74, 82, 138, 156, 286 Quinidine, 103, 105, 109, 111, 195, 206, 286 Quinine, 286 R Race, 74, 181, 274, 275, 286 Radiation, 22, 29, 149, 158, 169, 179, 244, 256, 271, 274, 286, 290, 299

Radioactive, 248, 268, 269, 271, 273, 278, 286, 287, 290 Radiofrequency ablation, 26, 52, 68, 74, 89, 91, 118, 119, 123, 198, 286 Radioimmunoassay, 247, 286 Radiological, 280, 286 Radiology, 4, 286, 287 Radiopharmaceutical, 265, 287 Random Allocation, 287 Randomization, 6, 13, 287 Randomized, 6, 12, 16, 21, 36, 46, 51, 52, 56, 57, 74, 91, 92, 94, 96, 102, 109, 116, 259, 287 Randomized clinical trial, 12, 46, 51, 52, 287 Randomized Controlled Trials, 36, 287 Reactivation, 14, 287 Reactive Oxygen Species, 33, 287 Receptor, 8, 33, 36, 44, 49, 182, 245, 286, 287, 291 Recombinant, 24, 40, 287, 298 Recombinant Proteins, 24, 287 Recombination, 265, 287 Rectum, 249, 258, 263, 264, 272, 287 Recur, 8, 280, 287 Reentry, 39, 42, 153, 288 Refer, 1, 242, 254, 258, 263, 273, 274, 277, 288, 291 Refraction, 288, 293 Refractory, 28, 33, 57, 75, 86, 118, 142, 145, 146, 201, 260, 288 Regimen, 259, 281, 288 Regurgitation, 38, 266, 288 Relapse, 202, 288 Reliability, 12, 159, 288 Remission, 287, 288 Renal failure, 151, 181, 257, 288 Renin, 182, 244, 288 Renin-Angiotensin System, 244, 288 Reperfusion, 10, 288 Reperfusion Injury, 288 Research Design, 49, 288 Resection, 80, 120, 288 Respiration, 245, 250, 276, 288 Responsive pacemaker, 44, 289 Restitution, 8, 289 Restoration, 103, 110, 138, 287, 288, 289, 299 Restrictive cardiomyopathy, 140, 289 Retina, 257, 274, 289 Retinal, 257, 279, 289 Retrograde, 155, 289

Index 311

Retrospective, 36, 100, 289 Retrospective study, 100, 289 Reversion, 137, 251, 289 Rheumatism, 289 Rheumatoid, 40, 289 Rheumatoid arthritis, 40, 289 Rhythmicity, 137, 168, 289 Risk patient, 6, 65, 289 Rod, 35, 253, 289 Rubber, 259, 289 Ryanodine, 33, 289 S Salivary, 258, 290 Salivary glands, 258, 290 Saphenous, 256, 290 Saphenous Vein, 256, 290 Sarcoid, 140, 290 Sarcoidosis, 290 Sarcolemma, 24, 290 Sarcoplasmic Reticulum, 9, 42, 290 Saturated fat, 25, 290 Scans, 25, 290 Scleroderma, 151, 181, 290 Sclerosis, 151, 181, 290 Screening, 30, 31, 36, 50, 61, 163, 185, 253, 290, 297 Secretion, 267, 268, 270, 290 Sediment, 290, 297 Segmentation, 5, 290 Segregation, 146, 247, 287, 290 Seizures, 257, 280, 290 Sella, 282, 290 Semisynthetic, 250, 291 Sensor, 143, 155, 291 Septal, 71, 77, 122, 244, 291 Septum, 39, 178, 246, 250, 291 Septum Pellucidum, 291 Sequencing, 28, 291, 294 Serine, 42, 291 Serotonin, 281, 291, 294 Serous, 261, 291 Serum, 25, 254, 273, 286, 291, 297 Sick Sinus Syndrome, 12, 26, 224, 291 Side effect, 22, 30, 38, 41, 156, 164, 205, 242, 291, 296 Signal Transduction, 10, 291 Signs and Symptoms, 288, 291 Sinoatrial Node, 141, 152, 162, 168, 173, 178, 179, 187, 191, 291, 292 Skeletal, 253, 271, 276, 286, 290, 292 Skeleton, 271, 284, 292 Skull, 292, 295

Sleep apnea, 13, 84, 292 Small intestine, 253, 259, 267, 271, 292 Smooth muscle, 182, 249, 263, 267, 271, 288, 292 Social Environment, 286, 292 Sodium, 30, 64, 118, 127, 242, 277, 278, 286, 292 Soft tissue, 45, 248, 292 Solitary Nucleus, 247, 292 Solvent, 241, 247, 292 Somatic, 267, 292, 297 Sotalol, 33, 52, 105, 112, 123, 128, 292 Sound wave, 255, 292 Spatial disorientation, 258, 292 Specialist, 228, 258, 292 Species, 250, 261, 267, 275, 286, 287, 293, 297, 299 Specificity, 37, 168, 242, 249, 293 Spectrum, 12, 154, 293 Sperm, 253, 293 Spinal cord, 252, 253, 266, 275, 277, 293, 294 Spleen, 161, 273, 290, 293 Stabilization, 191, 293 Staging, 290, 293 Steady state, 14, 293 Steel, 140, 253, 293, 297 Stem Cells, 42, 293 Stent, 149, 152, 156, 162, 163, 174, 293 Steroid, 250, 293 Stimulant, 206, 267, 271, 293 Stimulus, 144, 176, 188, 255, 259, 260, 262, 270, 271, 272, 293, 295 Stomach, 258, 261, 264, 267, 270, 292, 293 Stress, 33, 202, 246, 251, 279, 289, 293 Stroke Volume, 250, 294 Stroma, 280, 294 Styrene, 139, 140, 289, 294 Subacute, 269, 294 Subclinical, 269, 290, 294 Subcutaneous, 40, 259, 294 Substrate, 8, 16, 17, 29, 45, 136, 154, 172, 191, 259, 261, 294 Suction, 189, 294 Sudden cardiac death, 15, 48, 49, 156, 198, 294 Sudden death, 34, 91, 142, 184, 294 Sulfamoyl, 186, 294 Sumatriptan, 50, 294 Superior vena cava, 43, 121, 249, 292, 294 Suppression, 17, 56, 65, 77, 294


Supraventricular, 23, 40, 91, 128, 129, 135, 141, 142, 150, 168, 173, 181, 184, 294 Surgical Instruments, 169, 294 Sympathetic Nervous System, 181, 182, 244, 246, 294 Sympathomimetic, 261, 271, 278, 294 Symptomatic, 23, 26, 38, 52, 69, 126, 128, 129, 156, 157, 194, 263, 294 Synaptic, 291, 294 Synchrony, 163, 294 Syncope, 122, 222, 238, 295 Synovial, 40, 295 Systemic, 27, 140, 206, 245, 248, 257, 261, 267, 269, 290, 295, 298, 299 Systole, 176, 295 Systolic, 20, 38, 268, 295 T Tachyarrhythmia, 26, 71, 135, 139, 155, 160, 295 Tachycardia, Supraventricular, 9, 295 Tachycardia, Ventricular, 190, 295 Temporal, 45, 92, 115, 154, 274, 295 Teratogenic, 258, 295 Testosterone, 243, 295 Therapeutics, 68, 71, 74, 79, 92, 96, 141, 181, 207, 295 Thermal, 15, 258, 277, 295 Thoracic, 43, 52, 53, 54, 55, 56, 72, 76, 77, 80, 84, 85, 105, 111, 119, 120, 257, 295, 299 Thoracotomy, 134, 148, 170, 295 Thorax, 241, 294, 295, 297 Threonine, 42, 291, 295 Threshold, 9, 45, 100, 137, 144, 160, 175, 177, 262, 268, 295 Thrombin, 161, 185, 263, 282, 285, 295 Thromboembolism, 49, 51, 72, 98, 101, 104, 107, 110, 130, 138, 295 Thrombomodulin, 285, 295 Thromboplastin, 285, 295 Thrombosis, 7, 102, 104, 109, 111, 137, 185, 247, 285, 293, 296 Thrombus, 20, 67, 69, 73, 79, 101, 108, 200, 256, 269, 271, 276, 282, 296, 298 Thyroid, 44, 74, 181, 239, 268, 296 Thyroid Gland, 268, 296 Thyrotropin, 268, 296 Tin, 103, 109, 282, 296 Tissue Culture, 249, 296 Tomography, 31, 95, 254, 255, 296 Torsion, 269, 296

Toxic, iv, 30, 247, 250, 258, 259, 275, 294, 296 Toxicity, 10, 30, 142, 250, 259, 296 Toxicology, 214, 296 Toxins, 245, 249, 266, 269, 296 Trace element, 296 Trachea, 249, 296 Traction, 253, 296 Transduction, 10, 291, 296 Transfection, 248, 296 Transient Ischemic Attacks, 103, 110, 124, 296 Transmitter, 183, 241, 271, 274, 278, 297 Transplantation, 53, 73, 253, 269, 274, 297 Trauma, 134, 146, 170, 185, 257, 277, 297 Tumor Necrosis Factor, 40, 297 Tungsten, 251, 297 Tunica Intima, 260, 297 U Ultrasonography, 63, 297 Unconscious, 244, 268, 297 Uremia, 288, 297 Urethane, 140, 297 Urinalysis, 30, 297 Urinary, 247, 265, 297 Urine, 247, 258, 265, 277, 285, 297 Urogenital, 265, 297 Uterus, 252, 297 V Vaccine, 241, 285, 297 Vagal, 27, 62, 75, 95, 123, 297 Vagus Nerve, 292, 297 Valves, 143, 178, 298 Vascular endothelial growth factor, 102, 109, 298 Vascular Resistance, 243, 263, 298 Vasoactive, 182, 298 Vasoconstriction, 182, 249, 261, 298 Vasodilatation, 102, 108, 251, 298 Vasodilation, 244, 298 Vasodilator, 249, 263, 264, 267, 277, 278, 298 Vasomotor, 261, 298 Vector, 17, 44, 296, 298 Vena, 153, 298 Venous, 7, 31, 78, 140, 185, 247, 248, 252, 285, 298, 299 Venous blood, 248, 252, 298 Venous Pressure, 252, 298 Venous Thrombosis, 7, 185, 247, 298, 299 Ventricular, 11, 12, 14, 15, 20, 22, 23, 26, 28, 30, 33, 34, 35, 38, 45, 48, 50, 59, 62,

Index 313

64, 67, 78, 79, 84, 90, 96, 103, 110, 116, 118, 120, 121, 135, 137, 138, 139, 140, 141, 142, 144, 145, 147, 148, 150, 151, 152, 154, 155, 160, 163, 165, 166, 167, 172, 173, 176, 179, 180, 181, 183, 184, 187, 189, 190, 191, 196, 214, 243, 250, 263, 284, 294, 295, 298 Ventricular Dysfunction, 35, 38, 67, 90, 150, 181, 298 Ventricular fibrillation, 11, 34, 96, 135, 137, 139, 140, 142, 144, 150, 160, 172, 176, 180, 190, 298 Ventricular Function, 90, 137, 142, 167, 184, 298 Venules, 248, 250, 261, 298 Verapamil, 96, 103, 109, 118, 151, 201, 264, 298 Vertigo, 163, 264, 298 Veterinary Medicine, 102, 108, 213, 298 Viral, 30, 44, 296, 299 Viral vector, 44, 299 Virulence, 296, 299

Virus, 247, 265, 270, 282, 296, 299 Visceral, 247, 297, 299 Visceral Afferents, 247, 297, 299 Vitreous Hemorrhage, 257, 299 Vitro, 15, 27, 32, 267, 299 Vivo, 15, 17, 27, 31, 33, 42, 299 Voltage-gated, 24, 299 W Wakefulness, 257, 299 White blood cell, 244, 272, 273, 299 Windpipe, 296, 299 Withdrawal, 7, 257, 299 Wound Healing, 251, 299 X Xenograft, 244, 299 X-ray, 4, 22, 29, 239, 251, 254, 264, 278, 287, 290, 299 Y Yeasts, 281, 299 Z Zymogen, 285, 299


Index 315


Atrial Fibrillation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Atrial Fibrillation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Atrial Septal Defect - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Atrial Flutter - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Influenza A - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lipomas - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Barbiturates - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Cephalexin - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Lymphedema - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Vaginitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Feet - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Glioblastoma Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Female Infertility - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Living Will - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Benzene - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Erythema Multiforme - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Atrial Fibrillation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References