Table Of Content

Look for these other titles in the Braunwald’s Heart Disease Family Braunwald’s Heart Disease Companions Braunwald’s Heart Disease Review and Assessment Pierre Théroux Acute Coronary Syndromes Leonard S. Lilly Braunwald’s Heart Disease Review and Assessment Elliott M. Antman and Marc S. Sabatine Cardiovascular Therapeutics Braunwald’s Heart Disease Imaging Ziad Issa, John M. Miller, and Douglas P. Zipes Companions Clinical Arrhythmology and Electrophysiology Allen J. Taylor Christie M. Ballantyne Atlas of Cardiovascular Computed Tomography Clinical Lipidology Christopher M. Kramer and W. Gregory Hundley Darren K. McGuire and Nikolaus Marx Atlas of Cardiovascular Magnetic Resonance Diabetes in Cardiovascular Disease Ami E. Iskandrian and Ernest V. Garcia Douglas L. Mann and G. Michael Felker Atlas of Nuclear Cardiology Heart Failure Henry R. Black and William J. Elliott Coming Soon! Hypertension Deepak L. Bhatt Robert L. Kormos and Leslie W. Miller Cardiovascular Interventions Mechanical Circulatory Support David A. Morrow Roger S. Blumenthal, JoAnne M. Foody, Myocardial Infarction and Nathan D. Wong Preventive Cardiology Catherine M. Otto and Robert O. Bonow Valvular Heart Disease Mark A. Creager, Joshua A. Beckman, and Joseph Loscalzo Vascular Medicine xxvii BRAUNWALD’S HEART DISEASE A TEXTBOOK OF CARDIOVASCULAR MEDICINE TENTH EDITION BRAUNWALD’S HEART DISEASE A TEXTBOOK OF CARDIOVASCULAR MEDICINE Edited by Douglas L. Mann, Robert O. Bonow, MD MD, MS Lewin Chair and Professor of Medicine, Cell Biology, and Max and Lilly Goldberg Distinguished Professor of Physiology Cardiology Chief, Division of Cardiology Vice Chairman, Department of Medicine Washington University School of Medicine in St. Louis Director, Center for Cardiac Innovation Cardiologist-in-Chief Northwestern University Feinberg School of Medicine Barnes-Jewish Hospital Chicago, Illinois St. Louis, Missouri Douglas P. Zipes, Founding Editor and Online Editor MD Distinguished Professor Eugene Braunwald, MD, MD(Hon), Professor Emeritus of Medicine, Pharmacology, and Toxicology ScD(Hon), FRCP Director Emeritus, Division of Cardiology and the Distinguished Hersey Professor of Medicine Krannert Institute of Cardiology Harvard Medical School Indiana University School of Medicine Founding Chairman, TIMI Study Group Indianapolis, Indiana Brigham and Women’s Hospital Boston, Massachusetts Peter Libby, MD Mallinckrodt Professor of Medicine Harvard Medical School Chief, Cardiovascular Medicine Division Brigham and Women’s Hospital Boston, Massachusetts 1600 John F. Kennedy Blvd. Ste. 1800 Philadelphia, PA 19103-2899 BRAUNWALD’S HEART DISEASE: A TEXTBOOK Single-volume ISBN: 978-1-4557-5134-1 OF CARDIOVASCULAR MEDICINE, TENTH EDITION Two-volume ISBN: 978-1-4557-5133-4 Volume 1 PN: 9996096335 Copyright © 2015, 2012, 2008, 2005, 200 1, 1997, 1992, 1988, 1984, 1980 Volume 2 PN: 9996096394 b y Saunders, an imprint of Elsevier Inc. International edition ISBN: 978-0-323-29429-4 All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the Publisher. Details on how to seek permission, further information about the Publisher’s permissions policies, and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data Braunwald’s heart disease : a textbook of cardiovascular medicine / edited by Douglas L. Mann, Douglas P. Zipes, Peter Libby, Robert O. Bonow, Eugene Braunwald.—10th edition. p. ; cm. Heart disease Preceded by Braunwald’s heart disease / edited by Robert O. Bonow … [et al.] ; founding editor and online editor Eugene Braunwald. c2012. Includes bibliographical references and index. ISBN 978-1-4557-5134-1 (single-volume : hardcover : alk. paper)—ISBN 978-1-4557-5133-4 (two-volume set : hardcover : alk. paper)—ISBN 9996096335 (volume 1 : hardcover : alk. paper)—ISBN 9996096394 (volume 2 : hardcover : alk. paper)—ISBN 978-0-323-29429-4 (international edition : hardcover : alk. paper) I. Mann, Douglas L., editor. II. Zipes, Douglas P., editor. III. Libby, Peter, editor. IV. Bonow, Robert O., editor. V. Braunwald, Eugene, 1929- , editor. VI. Title: Heart disease. [DNLM: 1. Heart Diseases. 2. Cardiovascular Diseases. WG 210] 616.1′2–dc23 2014025014 Executive Content Strategist: Dolores Meloni Senior Content Development Specialist: Anne Snyder Publishing Services Manager: Anne Altepeter Project Manager: Louise King Designer: Steven Stave Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 To Laura, Erica, Jonathan, and Stephanie Joan, Debra, Jeffrey, and David Beryl, Oliver, and Brigitte Pat, Rob, and Sam Acknowledgments Completing a textbook the size and complexity of Braunwald’s Heart The editors are also grateful to our colleagues from all over the Disease clearly does not occur in a vacuum. The tenth edition owes world who have offered insightful suggestions to improve Heart a great deal to a great many individuals. First and foremost, we would Disease. We particularly wish to acknowledge the following individ- like to thank Dr. Eugene Braunwald for continuing to provide sage uals who have provided important feedback on numerous chapters: counsel at all stages of planning, writing, and editing of this book. Shabnam Madadi, MD, Cardiac Imaging Center, Shahid Rajaei Heart We also want to thank the incredibly supportive staff at Elsevier, who Center, Tehran, Iran; Azin Alizadeh Asl, MD, and Anita Sadeghpour, enabled the editors to make improvements to the content and visual MD, Tabriz University of Medical Sciences and Madani Heart Hospi- design of the book as it was being compiled. In this regard, we would tal, Tabriz, Iran; Leili Pourafkari, MD, Razi Hospital, Tabriz, Iran; like to recognize several Elsevier staff members for their forbearance Banasiak Waldemar, MD, Centre for Heart Disease, Military Hospi- and indefatigable assistance: Dolores Meloni, executive content strat- tal, Wroclaw, Poland; Carlos Benjamín Alvarez, MD, PhD, Sacré egist, for her boundless energy and enthusiasm for this book; Anne Coeur Institute, Buenos Aires, Argentina; and Elias B. Hanna, MD, Snyder, senior content development specialist, for everything all of Division of Cardiology, Louisiana State University, New Orleans, the time; and Louise King, project manager, whose attention to detail Louisiana. and flexibility were measureless. vi Contributors Keith D. Aaronson, MD, MS Joshua A. Beckman, MD Professor of Internal Medicine, Division of Cardiovascular Associate Professor of Medicine, Harvard Medical School; Medicine, University of Michigan Health System, Ann Arbor, Cardiovascular Medicine Division, Brigham and Women’s Michigan Hospital; Associate Medical Director, VasCore, Massachusetts Mechanical Circulatory Support General Hospital, Boston, Massachusetts Anesthesia and Noncardiac Surgery in Patients with Heart William T. Abraham, MD Disease Professor of Internal Medicine, Physiology, and Cell Biology, Chair of Excellence in Cardiovascular Medicine, Director, Division of Donald M. Bers, PhD Cardiovascular Medicine, Deputy Director, The Davis Heart and Distinguished Professor and Chair, Pharmacology, University of Lung Research Institute, The Ohio State University, Columbus, California Davis, Davis, California Ohio Mechanisms of Cardiac Contraction and Relaxation Devices for Monitoring and Managing Heart Failure Michael A. Bettman, MD Michael A. Acker, MD Professor Emeritus of Radiology, Wake Forest University School of Chief, Division of Cardiovascular Surgery, Director, Penn Medicine Medicine, Winston-Salem, North Carolina Heart and Vascular Center, University of Pennsylvania Health The Chest Radiograph in Cardiovascular Disease System, Philadelphia, Pennsylvania Surgical Management of Heart Failure Deepak L. Bhatt, MD, MPH Senior Investigator, TIMI Study Group, Executive Director, Michael J. Ackerman, MD, PhD Interventional Cardiovascular Programs, Heart and Vascular Windland Smith Rice Cardiovascular Genomics Research Professor, Center, Brigham and Women’s Hospital; Professor of Medicine, Professor of Medicine, Pediatrics, and Pharmacology, Director, Harvard Medical School, Boston, Massachusetts Long QT Syndrome/Genetic Heart Rhythm Clinic, Director, Mayo Coronary Arteriography and Intracoronary Imaging; Clinic Windland Smith Rice Sudden Death Genomics Laboratory, Percutaneous Coronary Intervention; Treatment of Mayo Clinic, Rochester, Minnesota Noncoronary Obstructive Vascular Disease Genetics of Cardiac Arrhythmias William E. Boden, MD Elliott M. Antman, MD Chief of Medicine, Albany Stratton Veterans Affairs Medical Center; Professor of Medicine, Associate Dean for Clinical/Translational Vice Chairman, Department of Medicine, Albany Medical Center; Research, Harvard Medical School; Senior Investigator, TIMI Professor of Medicine, Albany Medical College, Albany, Study Group, Brigham and Women’s Hospital, Boston, New York Massachusetts Stable Ischemic Heart Disease Critical Evaluation of Clinical Trials Robert O. Bonow, MD, MS Larry M. Baddour, MD Max and Lilly Goldberg Distinguished Professor of Cardiology, Vice Professor of Medicine, Mayo Clinic, Rochester, Minnesota Chairman, Department of Medicine, Director, Center for Cardiac Cardiovascular Infections Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois Aaron Baggish, MD Appropriate Use Criteria: Echocardiography; Nuclear Cardiovascular Performance Program, Massachusetts General Cardiology; Cardiac Catheterization; Appropriate Use Hospital; Assistant Professor of Medicine, Harvard Medical Criteria: Multimodality Imaging in Stable Ischemic Heart School, Boston, Massachusetts Disease and Heart Failure; Care of Patients with End-Stage Exercise and Sports Cardiology Heart Disease; Valvular Heart Disease; Guidelines: Infective Endocarditis C. Noel Bairey Merz, MD Women’s Guild Endowed Chair in Women’s Health, Director, Barbra Eugene Braunwald, MD, MD(Hon), ScD(Hon), FRCP Streisand Women’s Heart Center, Director, Preventive Cardiac Distinguished Hersey Professor of Medicine, Harvard Medical Center; Director, Linda Joy Pollin Women’s Healthy Heart School; Founding Chairman, TIMI Study Group, Brigham and Program; Professor of Medicine, Cedars-Sinai Medical Center, Los Women’s Hospital, Boston, Massachusetts Angeles, California Non–ST Elevation Acute Coronary Syndromes Cardiovascular Disease in Women Alan C. Braverman, MD Gary J. Balady, MD Alumni Endowed Professor in Cardiovascular Diseases, Department Director, Non Invasive Cardiovascular Laboratories, Boston Medical of Medicine, Washington University School of Medicine in St. Center; Professor of Medicine, Boston University School of Louis, St. Louis, Missouri Medicine, Boston, Massachusetts Diseases of the Aorta Exercise Testing vii viii J. Douglas Bremner, MD Stephen Devries, MD Professor of Psychiatry and Radiology, Director, Emory Clinical Executive Director, Gaples Institute for Integrative Cardiology, Neuroscience Research Unit, Emory University School of Deerfield, Illinois; Associate Professor of Medicine, Division of s r Medicine; Director, Mental Health Research, Atlanta Veterans Cardiology, Northwestern University, Chicago, Illinois o t Affairs Medical Center, Atlanta, Georgia Integrative Approaches to the Management of Patients with u b Psychiatric and Behavioral Aspects of Cardiovascular Disease Heart Disease ri t n Julie E. Buring, MD Neal W. Dickert, MD, PhD o C Professor of Medicine, Brigham and Women’s Hospital; Professor of Assistant Professor. Department of Medicine, Division of Epidemiology, Harvard Medical School; Harvard School of Cardiology, School of Medicine, Department of Epidemiology, Public Health, Boston, Massachusetts Rollins School of Public Health, Emory University, Atlanta, Risk Markers and the Primary Prevention of Cardiovascular Georgia Disease Ethics in Cardiovascular Medicine Hugh G. Calkins, MD Vasken Dilsizian, MD Professor of Medicine, Director, Cardiac Arrhythmia Service, Professor of Medicine and Radiology, University of Maryland Director, Johns Hopkins Arrhythmogenic Right Ventricular School of Medicine; Chief, Division of Nuclear Medicine, Dysplasia Program, The Johns Hopkins Hospital, Baltimore, University of Maryland Medical Center, Baltimore, Maryland Maryland Nuclear Cardiology; Appropriate Use Criteria: Multimodality Hypotension and Syncope Imaging in Ischemic Heart Disease and Heart Failure Christopher P. Cannon, MD Dirk J. Duncker, MD, PhD Cardiovascular Medicine Division, Brigham and Women’s Hospital; Professor of Experimental Cardiology, Department of Cardiology, Professor of Medicine, Harvard Medical School; Executive Erasmus University Medical Center, Rotterdam, The Netherlands Director, Cardiometabolic Trials, Harvard Clinical Research Coronary Blood Flow and Myocardial Ischemia Institute, Boston, Massachusetts Approach to the Patient with Chest Pain; Non–ST Elevation Ezekiel J. Emanuel, MD, PhD Acute Coronary Syndromes Vice Provost for Global Initiatives, Diane V.S. Levy and Robert M. Levy University Professor, Chairperson, Department of Medical John M. Canty, Jr., MD Ethics and Health Policy, University of Pennsylvania, Albert and Elizabeth Rekate Professor of Medicine, Division of Philadelphia, Pennsylvania Cardiovascular Medicine, Western New York Veterans Affairs Ethics in Cardiovascular Medicine Healthcare System, University at Buffalo, Buffalo, New York Coronary Blood Flow and Myocardial Ischemia Rodney H. Falk, MD Director, Cardiac Amyloidosis Program, Brigham and Women’s John D. Carroll, MD Hospital; Associate Clinical Professor of Medicine, Harvard Professor of Medicine, University of Colorado Denver, Denver, Medical School, Boston, Massachusetts Colorado; Director of Interventional Cardiology and Co-Medical The Dilated, Restrictive, and Infiltrative Cardiomyopathies Director, Cardiac and Vascular Center, University of Colorado Hospital, Aurora, Colorado James C. Fang, MD Transcatheter Therapies for Structural Heart Disease in Adults Professor of Medicine, Chief, Division of Cardiovascular Medicine, Executive Director, Cardiovascular Service Line, University of Augustin Castellanos, MD Utah Health Sciences Center, Salt Lake City, Utah Emeritus Professor of Medicine, University of Miami Miller School The History and Physical Examination: An Evidence-Based of Medicine, Miami, Florida Approach Cardiac Arrest and Sudden Cardiac Death G. Michael Felker, MD, MHS Ming Hui Chen, MD, MSc Associate Professor of Medicine, Division of Cardiology, Duke Boston Children’s Hospital and Dana Farber Cancer Institute, University School of Medicine, Durham, North Carolina Director, Cardiovascular Health for Cancer Survivors; Assistant Diagnosis and Management of Acute Heart Failure Professor of Medicine, Harvard Medical School, Boston, Massachusetts Stacy D. Fisher, MD Cardiovascular Complications of Cancer Therapeutic Agents Director of Women’s and Complex Heart Diseases, Medicine, Cardiology, and Pediatric Cardiology, University of Maryland Leslie T. Cooper, Jr., MD Comprehensive Heart Center, Baltimore, Maryland Director, Gonda Vascular Center, Mayo Clinic, Rochester, Minnesota Cardiovascular Abnormalities in HIV-Infected Individuals Myocarditis Lee A. Fleisher, MD Mark A. Creager, MD Robert D. Dripps Professor and Chair, Anesthesiology and Critical Director, Vascular Center, Brigham and Women’s Hospital; Simon C. Care, Professor of Medicine, Perelman School of Medicine at the Fireman Scholar in Cardiovascular Medicine, Professor of University of Pennsylvania, Philadelphia, Pennsylvania Medicine, Harvard Medical School, Boston, Massachusetts Anesthesia and Noncardiac Surgery in Patients with Heart Peripheral Artery Diseases Disease Charles J. Davidson, MD Thomas Force, MD Chief, Clinical Cardiology, Medical Director, Bluhm Cardiovascular Professor of Medicine, Division of Cardiovascular Medicine, Institute, Northwestern Memorial Hospital; Professor of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee Northwestern University Feinberg School of Medicine, Chicago, Cardiovascular Complications of Cancer Therapeutic Agents Illinois Cardiac Catheterization ix William K. Freeman, MD Sarah J. Goodlin, MD Professor of Medicine, Mayo Clinic College of Medicine, Chief, Geriatrics, Portland Veterans Affairs Medical Center; Rochester, Minnesota Associate Professor, Oregon Health and Science University, C Cardiovascular Infections Portland, Oregon o n Care of Patients with End-Stage Heart Disease t J. Michael Gaziano, MD, MPH r ib Chief, Division of Aging, Brigham and Women’s Hospital; Scientific William J. Groh, MD, MPH u t Director, Massachusetts Veterans Epidemiology Research and Associate Professor of Medicine, Indiana University School of o r Information Center, Veterans Administration Boston Healthcare Medicine, Indianapolis, Indiana s System; Professor of Medicine, Harvard Medical School, Boston, Neurologic Disorders and Cardiovascular Disease Massachusetts Global Burden of Cardiovascular Disease Martha Gulati, MD, MS Associate Professor of Medicine, Division of Cardiology, Associate Thomas A. Gaziano, MD, MSc Professor of Clinical Public Health, Division of Epidemiology, Assistant Professor, Harvard Medical School; Cardiovascular Sarah Ross Soter Chair, Women’s Cardiovascular Health, Section Medicine Division, Brigham and Women’s Hospital, Boston, Director, Preventive Cardiology and Women’s Cardiovascular Massachusetts Health, The Ohio State University Wexner Medical Center, Global Burden of Cardiovascular Disease Columbus, Ohio Cardiovascular Disease in Women Jacques Genest, MD Professor of Medicine, Cardiology, McGill University; Scientific Roger J. Hajjar, MD Director, Centre for Innovative Medicine, McGill University Health Director, Cardiovascular Research Center, Icahn School of Centre, Montreal, Quebec, Canada Medicine at Mount Sinai, New York, New York Lipoprotein Disorders and Cardiovascular Disease Cardiovascular Regeneration and Gene Therapy Robert E. Gerszten, MD Joshua M. Hare, MD Director of Clinical and Translational Research, Massachusetts Louis Lemberg Professor of Medicine, Cardiovascular Division, General Hospital Institute for Heart, Vascular, and Stroke Care; Director, Interdisciplinary Stem Cell Institute, University of Miami Professor of Medicine, Harvard Medical School; Senior Associate Miller School of Medicine, Miami, Florida Member, Broad Institute, Boston, Massachusetts Cardiovascular Regeneration and Gene Therapy Biomarkers, Proteomics, Metabolomics, and Personalized Medicine Gerd Hasenfuss, MD Professor of Medicine, Chair, Department of Cardiology and Linda Gillam, MD, MPH Pneumology, Chair, Heart Center, University of Goettingen; Chairperson, Department of Cardiovascular Medicine, Morristown Chair, Heart Research Center, DZHK (German Center of Medical Center, Atlantic Health System, Morristown, New Jersey Cardiovascular Research), Goettingen, Germany Echocardiography Pathophysiology of Heart Failure Geoffrey S. Ginsburg, MD, PhD Ray E. Hershberger, MD Executive Director, Center for Personalized and Precision Medicine, Professor of Medicine, Director, Division of Human Genetics, Duke University Health Systems; Director, Genomic Medicine, Division of Cardiovascular Medicine, Section of Heart Failure Institute for Genome Sciences and Policy, Professor of Medicine, and Cardiac Transplantation, The Ohio State University Wexner Pathology and Biomedical Engineering, Duke University School Medical Center, Columbus, Ohio of Medicine, Durham, North Carolina The Dilated, Restrictive, and Infiltrative Cardiomyopathies Personalized and Precision Cardiovascular Medicine L. David Hillis, MD Robert P. Giugliano, MD, SM Professor and Chair, Internal Medicine, The University of Texas Physician, Cardiovascular Medicine Division, Brigham and Health Science Center, San Antonio, Texas Women’s Hospital; Associate Professor of Medicine, Harvard Chemical Cardiomyopathies Medical School, Boston, Massachusetts Non–ST Elevation Acute Coronary Syndromes William E. Hopkins, MD Associate Professor of Medicine, The University of Vermont; Ary L. Goldberger, MD Attending Cardiologist, Fletcher Allen Health Care, Burlington, Professor of Medicine, Harvard Medical School; Director, Margret Vermont and H.A. Rey Institute for Nonlinear Dynamics in Medicine; Pericardial Diseases Associate Chief, Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Boston, Massachusetts Marc Humbert, MD, PhD Electrocardiography Professor of Respiratory Medicine, Service de Pneumologie, Hôpital Bicêtre; Assistance, Publique Hôpitaux de Paris, Université Samuel Z. Goldhaber, MD Paris-Sud, Paris, France Professor of Medicine, Harvard Medical School; Director, Pulmonary Hypertension Thrombosis Research Group; Senior Staff Physician, Cardiovascular Medicine Division, Brigham and Women’s James L. Januzzi, Jr., MD Hospital, Boston, Massachusetts Professor of Medicine, Harvard Medical School; Roman W. Pulmonary Embolism De Sanctis Endowed Distinguished Clinical Scholar, Division of Cardiology, Massachusetts General Hospital, Boston, Larry B. Goldstein, MD Massachusetts Professor of Neurology and Director, Duke Stroke Center, Duke Clinical Assessment of Heart Failure University; Staff Neurologist, Durham Veterans Affairs Medical Center, Durham, North Carolina Prevention and Management of Ischemic Stroke