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 EDITION

12

HEART
B R A U N WA L D’S

DISEASE
A TEXTBOOK OF CARDIOVASCULAR MEDICINE

Edited by
PETER LIBBY, MD DEEPAK L. BHATT, MD, MPH
Mallinckrodt Professor of Medicine Executive Director of Interventional Cardiovascular Programs
Harvard Medical School Brigham and Women’s Hospital
Brigham and Women’s Hospital Senior Physician
Boston, Massachusetts Brigham and Women’s Hospital
Professor of Medicine
ROBERT O. BONOW, MD Harvard Medical School
Max and Lilly Goldberg Distinguished Professor of Cardiology Boston, Massachusetts
Department of Medicine
Northwestern University Feinberg School of Medicine SCOTT D. SOLOMON, MD
Chicago, Illinois The Edward D. Frohlich Distinguished Chair
Professor of Medicine
DOUGLAS L. MANN, MD Harvard Medical School
Lewin Distinguished Professor of Cardiovascular Disease Senior Physician
Washington University School of Medicine in St. Louis Brigham and Women’s Hospital
Saint Louis, Missouri Boston, Massachusetts

GORDON F. TOMASELLI, MD
Professor of Medicine (Cardiology) Founding Editor and Online Editor
The Marilyn and Stanley M. Katz Dean
Albert Einstein College of Medicine EUGENE BRAUNWALD, MD,
Executive Vice President and Chief Academic Officer MD(Hon), ScD(Hon), FRCP
Montefiore Medicine Distinguished Hersey Professor of Medicine
Bronx, New York Harvard Medical School
Founding Chairman, TIMI Study Group
Brigham and Women’s Hospital
Boston, Massachusetts
ELSEVIER
1600 John F. Kennedy Blvd.
Ste. 1800
Philadelphia, PA 19103-­2899

BRAUNWALD’S HEART DISEASE: A TEXTBOOK OF TWO-­VOLUME SET ISBN: 978-­0-­323-­72219-­3

CARDIOVASCULAR MEDICINE, TWELFTH EDITION SINGLE VOLUME ISBN: 978-­0-­323-­82467-­5
Copyright © 2022 by Elsevier Inc. INTERNATIONAL EDITION ISBN: 978-­0-­323-­82468-­2

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. Permissions may be sought directly from Elsevier’s
Rights Department: phone: (+1) 215-­239-­3804 (US) or (+44) 1-­865-­843830 (UK); fax: (+44) 1-­865-­853333; e-­mail:
healthpermissions@elsevier.com. You may also complete your request on-­line via the Elsevier website at
http://www.elsevier.com/permissions.

Notice

Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or
appropriate. 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
the practitioner, relying on their own experience and knowledge of the patient, 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 assume any liability
for any injury and/or damage to persons or property arising out of or related to any use of the material
contained in this book.

The Publisher

Previous editions copyrighted 2019, 2015, 2012, 2008, 2005, 2001, 1997, 1992, 1988, 1984, 1980 by Elsevier Inc.

Library of Congress Control Number: 2021936447

Executive Content Strategists: Dolores Meloni, Robin Carter

Senior Content Development Specialist: Anne Snyder
Publishing Services Manager: Catherine Jackson
Senior Project Manager: John Casey
Design Direction: Renee Duenow

About the cover:

Professor C. Michael Gibson is well known in interventional cardiology for his many contributions to clinical sci-
ence. He has had leadership positions in many pivotal clinical trials that have influenced our practice and guidelines.
He originated the TIMI myocardial perfusion grade. He currently leads the Baim Institute for Clinical Research, an
academic research organization at Boston’s Beth Isræl Hospital. Beyond his investigative prowess, Professor Gibson
is an unusually talented artist. The editor-­in-­chief was delighted that he agreed to provide art for the cover for this
12th edition of Braunwald’s Heart Disease. This addition is particularly appropriate because of Dr. Gibson’s long-­
term association with Dr. Braunwald’s research in ischemic heart disease. The editors are proud to have his artistic
rendition of the now classic Heart Disease logo grace the cover of our book.

Printed in United States of America

9 8 7 6 5 4 3 2 1
 To
Beryl, Oliver, and Brigitte
Pat, Rob, Sam, Laura, and Yoko
Benjamin Tan
Charlene, Sarah, Emily, and Matthew
Shanthala,Vinayak, Arjun, Ram, and Raj
Caren, Will and Lyz, Katie and Zach, and Dan
 Contributors

Keith D. Aaronson, MD, MS Sadeer Al-­Kindi, MD

Bertram Pitt MD Collegiate Professor of Cardiovascular Medicine Assistant Professor of Medicine
Professor of Internal Medicine Case Western Reserve University
Division of Cardiovascular Medicine Harrington Heart and Vascular Institute
University of Michigan University Hospitals Cleveland Medical Center
Ann Arbor, Michigan Cleveland, Ohio
Chapter 59. Mechanical Circulatory Support Chapter 3. Impact of the Environment on Cardiovascular Health

Michael J. Ackerman, MD, PhD Nandan S. Anavekar, MBBCh

Windland Smith Rice Cardiovascular Genomics Research Professor Professor of Medicine
Professor of Medicine, Pediatrics, and Pharmacology Department of Cardiovascular Diseases
Mayo Clinic College of Medicine and Science Department of Radiology
Department of Cardiovascular Medicine (Division of Heart Rhythm Mayo Clinic College of Medicine and Science
Services and the Windland Smith Rice Genetic Heart Rhythm Rochester, Minnesota
Clinic) Chapter 80. Infectious Endocarditis and Infections of Indwelling
Department of Molecular Pharmacology & Experimental Devices
Therapeutics (Windland Smith Rice Sudden Death Genomics
Laboratory) Zachi Attia, PhD
Department of Pediatric and Adolescent Medicine (Division of Department of Cardiovascular Medicine
Pediatric Cardiology) Mayo Clinic College of Medicine and Science
Mayo Clinic Rochester, Minnesota
Rochester, Minnesota Chapter 11. Artificial Intelligence in Cardiovascular Medicine
Chapter 63. Genetics of Cardiac Arrhythmias
Sonya V. Babu-­Narayan, MBBS, BSc, PhD, FRCP
Philip A. Ades, MD Adult Congenital Heart Disease
Endowed Professor of Medicine Royal Brompton Hospital
Division of Cardiology Reader, National Heart and Lung Institute
University of Vermont College of Medicine Imperial College London
Director, Cardiac Rehabilitation and Prevention London, United Kingdom
University of Vermont Medical Center Chapter 82. Congenital Heart Disease in the Adolescent and
Burlington,Vermont Adult
Chapter 15. Exercise Physiology and Exercise Electrocardiographic
Testing Larry M. Baddour, MD
Professor of Medicine
Christine M. Albert, MD Mayo Clinic College of Medicine and Science
Chair and Professor of Cardiology Rochester, Minnesota
Smidt Heart Institute, Cedars-­Sinai Medical Center Chapter 80. Infectious Endocarditis and Infections of Indwelling
Los Angeles, California Devices
Chapter 70. Cardiac Arrest and Sudden Cardiac Death
Aaron L. Baggish, MD
Michelle A. Albert, MD, MPH Associate Professor of Medicine
Professor of Medicine Harvard Medical School
Director, Center for the Study of Adversity and Cardiovascular Disease Director, Cardiovascular Performance Program
(NURTURE Center) Massachusetts General Hospital
University of California at San Francisco Boston, Massachusetts
San Francisco, California Chapter 32. Exercise and Sports Cardiology
Chapter 93. Heart Disease in Racially and Ethnically Diverse
Populations C. Noel Bairey Merz, MD
Women’s Guild Endowed Chair in Women’s Health
Mark J. Alberts, MD Director, Barbra Streisand Women’s Heart Center
Chief of Neurology Erika J. Glazer Women’s Heart Research Initiative Director
Hartford Hospital Director, Linda Joy Pollin Women’s Heart Health Program
Hartford, Connecticut; Barbra Streisand Women’s Heart Center
Co-­Physician-­in-­Chief Cedars-­Sinai Heart Institute
Ayer Neuroscience Institute Los Angeles, California
Hartford HealthCare Chapter 91. Cardiovascular Disease in Women
Professor of Neurology
University of Connecticut
Storrs, Connecticut
Chapter 45. Prevention and Management of Ischemic Stroke

vi
 vii
George L. Bakris, MD, MA Ron Blankstein, MD
Professor of Medicine Associate Director, Cardiovascular Imaging Program
Section of Endocrinology, Diabetes and Metabolism Director, Cardiac Computed Tomography

Contributors
Director, American Heart Association Comprehensive Hypertension Co-­Director, Cardiovascular Imaging Training Program
Center Brigham and Women’s Hospital
UChicago Medicine Professor of Medicine and Radiology
Chicago, Illinois Harvard Medical School
Chapter 26. Systemic Hypertension: Mechanisms, Diagnosis, and Boston, Massachusetts
Treatment Chapter 20. Cardiac Computed Tomography

Gary J. Balady, MD Erin A. Bohula, MD, DPhil

Professor of Medicine TIMI Study Group and Division of Cardiology
Boston University School of Medicine Brigham and Women’s Hospital
Director, Non-­Invasive Cardiovascular Laboratories Harvard Medical School
Boston Medical Center Boston, Massachusetts
Boston, Massachusetts Chapter 38. ST-­Elevation Myocardial Infarction: Management
Chapter 15. Exercise Physiology and Exercise Electrocardiographic
Testing Marc P. Bonaca, MD, MPH
Executive Director
David T. Balzer, MD CPC Clinical Research
Professor of Pediatrics Professor of Medicine
Division of Pediatric Cardiology Cardiology and Vascular Medicine
Washington University School of Medicine in St. Louis University of Colorado
Saint Louis, Missouri Aurora, Colorado
Chapter 83. Catheter-­Based Treatment of Congenital Heart Disease in Chapter 35. Approach to the Patient with Chest Pain
Adults Chapter 43. Peripheral Artery Diseases

Joshua A. Beckman, MD Robert O. Bonow, MD

Professor of Medicine Max and Lilly Goldberg Distinguished Professor of Cardiology
Division of Cardiovascular Medicine Department of Medicine
Vanderbilt University College of Medicine Northwestern University Feinberg School of Medicine
Director, Section of Vascular Medicine Chicago, Illinois
Vanderbilt University Medical Center Chapter 72. Aortic Valve Stenosis
Nashville, Tennessee Chapter 73. Aortic Regurgitation
Chapter 23. Anesthesia and Noncardiac Surgery in Patients with Heart Chapter 76. Mitral Regurgitation
Disease
Barry A. Borlaug, MD
Donald M. Bers, PhD Professor of Medicine
Distinguished Professor and Chair Mayo Medical School
Department of Pharmacology Director, Circulatory Failure Research
University of California, Davis Consultant, Cardiovascular Diseases
Davis, California Mayo Clinic College of Medicine and Science
Chapter 46. Mechanisms of Cardiac Contraction and Relaxation Rochester, Minnesota
Chapter 46. Mechanisms of Cardiac Contraction and Relaxation
Aruni Bhatnagar, PhD
Professor of Medicine Jason S. Bradfield, MD
University of Louisville Associate Professor of Medicine
Louisville, Kentucky Director, Specialized Program for Ventricular Tachycardia
Chapter 28. Cardiovascular Disease Risk of Nicotine and Tobacco UCLA Cardiac Arrhythmia Center
Products Ronald Reagan UCLA Medical Center
Los Angeles, California
Deepak L. Bhatt, MD, MPH Chapter 102. Cardiovascular Manifestations of Autonomic Disorders
Executive Director of Interventional Cardiovascular Programs
Brigham and Women’s Hospital Eugene Braunwald, MD, MD(Hon), ScD(Hon), FRCP
Senior Physician Distinguished Hersey Professor of Medicine
Brigham and Women’s Hospital Harvard Medical School
Professor of Medicine Founding Chairman, TIMI Study Group
Harvard Medical School Brigham and Women’s Hospital
Boston, Massachusetts Boston, Massachusetts
Chapter 41. Percutaneous Coronary Intervention Chapter 1. Cardiovascular Disease: Past, Present, and Future
Chapter 44. Treatment of Noncoronary Obstructive Vascular Disease Chapter 39. Non-­ST Elevation Acute Coronary Syndromes

Bernadette Biondi, MD Alan C. Braverman, MD

Professor of Internal Medicine Alumni Endowed Professor in Cardiovascular Diseases
Department of Clinical Medicine and Surgery Director, Marfan Syndrome and Aortopathy Clinic
Federico II University Washington University School of Medicine in St. Louis
Naples, Italy Director, Inpatient Cardiology Firm
Chapter 96. Endocrine Disorders and Cardiovascular Disease Barnes-­Jewish Hospital
Saint Louis, Missouri
Chapter 42. Diseases of the Aorta
 viii
John E. Brush Jr., MD Mark A. Creager, MD
Senior Medical Director Professor of Medicine and Surgery
Sentara Health Research Center Geisel School of Medicine at Dartmouth
CONTRIBUTORS

Sentara Healthcare Hanover, New Hampshire;

Professor of Medicine Director, Heart and Vascular Center
Department of Internal Medicine Heart and Vascular Center
Eastern Virginia Medical School Dartmouth-­Hitchcock Medical Center
Norfolk,Virginia Lebanon, New Hampshire
Chapter 5. Clinical Decision-­Making in Cardiology Chapter 43. Peripheral Artery Diseases

Hugh Calkins, MD Paul C. Cremer, MD

Catherine Ellen Poindexter Professor of Cardiology Assistant Professor of Medicine
Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve
Director, Cardiac Arrhythmia Service University
The Johns Hopkins Medical Institutions Associate Director of Cardiovascular Training Program
Baltimore, Maryland Cleveland Clinic Foundation
Chapter 66. Atrial Fibrillation: Clinical Features, Mechanisms, and Cleveland Clinic
Management Cleveland, Ohio
Chapter 71. Hypotension and Syncope Chapter 86. Pericardial Diseases

John M. Canty Jr., MD Juan A. Crestanello, MD

SUNY Distinguished and Albert and Elizabeth Rekate Professor of Professor of Surgery
Medicine Mayo Clinic College of Medicine and Science
Division of Cardiovascular Medicine Rochester, Minnesota
Jacobs School of Medicine and Biomedical Sciences Chapter 80. Infectious Endocarditis and Infections of Indwelling Devices
University at Buffalo
Buffalo, New York Anne B. Curtis, MD
Chapter 36. Coronary Blood Flow and Myocardial Ischemia Charles and Mary Bauer Professor and Chair
SUNY Distinguished Professor
Robert M. Carney, PhD Department of Medicine
Professor of Psychiatry Jacobs School of Medicine and Biomedical Sciences
Washington University School of Medicine in St. Louis University at Buffalo
Saint Louis, Missouri Buffalo, New York
Chapter 99. Psychiatric and Psychosocial Aspects of Cardiovascular Chapter 61. Approach to the Patient with Cardiac Arrhythmias
Disease
George D. Dangas, MD, PhD
Y.S. Chandrashekhar, MD Professor of Medicine (Cardiology)
Professor of Medicine Zena and Michael A Wiener Cardiovascular Institute
Division of Cardiology Icahn School of Medicine at Mount Sinai
University of Minnesota New York, New York
Chief of Cardiology Chapter 21. Coronary Angiography and Intravascular Imaging
VA Medical Center
Minneapolis, Minnesota James P. Daubert, MD
Chapter 75. Mitral Stenosis Professor of Medicine
Cardiology (Electrophysiology)
Peng-­Shen Chen, MD Duke University Medical Center
Cedars-­Sinai Medical Center Durham, North Carolina
Los Angeles, California Chapter 69. Pacemakers and Implantable Cardioverter-­Defibrillators
Chapter 71. Hypotension and Syncope
James A. de Lemos, MD
Mina K. Chung, MD Professor of Medicine
Professor of Medicine Sweetheart Ball-­Kern Wildenthal MD PhD Distinguished Chair in
Cardiovascular and Metabolic Sciences Cardiology
Lerner Research Institute UT Southwestern Medical Center
Cleveland Clinic Lerner College of Medicine of Case Western Reserve Dallas, Texas
University Chapter 40. Stable Ischemic Heart Disease
Staff, Cardiovascular Medicine
Cleveland Clinic Jean-­Pierre Després, PhD
Cleveland, Ohio Professor
Chapter 69. Pacemakers and Implantable Cardioverter-­Defibrillators Kinesiology Department
Université Laval
Leslie T. Cooper Jr., MD Scientific Director
Professor of Medicine VITAM – Centre de recherche en santé durable
Chair, Department of Vascular Medicine Centre intégré universitaire de santé et de services sociaux de la
Mayo Clinic Capitale-­Nationale
Jacksonville, Florida Québec City, Québec, Canada
Chapter 55. Myocarditis Chapter 30. Obesity: Medical and Surgical Management
 ix
Stephen Devries, MD G. Michael Felker, MD, MHS
Executive Director Professor of Medicine
Gaples Institute for Integrative Cardiology Vice Chief for Clinical Research

Contributors
Deerfield, Illinois; Division of Cardiology
Division of Cardiology Duke University School of Medicine
Northwestern University Feinberg School of Medicine Director, Cardiovascular Research
Chicago, Illinois Duke Clinical Research Institute
Chapter 34. Integrative Approaches to the Management of Patients with Durham, North Carolina
Heart Disease Chapter 49. Diagnosis and Management of Acute Heart Failure

Marcelo F. Di Carli, MD Jerome L. Fleg, MD

Seltzer Family Professor of Radiology and Medicine Medical Officer
Harvard Medical School Division of Cardiovascular Sciences
Executive Director, Cardiovascular Imaging Program National Heart, Lung, and Blood Institute
Chief, Division of Nuclear Medicine and Molecular Imaging Bethesda, Maryland
Brigham and Women’s Hospital Chapter 90. Cardiovascular Disease in Older Adults
Boston, Massachusetts
Chapter 18. Nuclear Cardiology Lee A. Fleisher, MD
Professor
Sharmila Dorbala, MD, MPH Anesthesiology and Critical Care
Professor of Radiology Professor of Medicine
Harvard Medical School University of Pennsylvania Perelman School of Medicine
Director, Nuclear Cardiology Philadelphia, Pennsylvania
Division of Nuclear Medicine and Molecular Imaging Chapter 23. Anesthesia and Noncardiac Surgery in Patients with Heart
Brigham and Women’s Hospital Disease
Boston, Massachusetts
Chapter 18. Nuclear Cardiology Daniel E. Forman, MD
Professor of Medicine
Adam L. Dorfman, MD University of Pittsburgh
Professor Chair, Section of Geriatric Cardiology
Departments of Pediatrics and Radiology Divisions of Geriatrics and Cardiology
Director, Non-­Invasive Imaging, Division of Pediatric Cardiology University of Pittsburgh Medical Center
University of Michigan Medical School Director, Cardiac Rehabilitation
C. S. Mott Children’s Hospital VA Pittsburgh Healthcare System
Ann Arbor, Michigan Pittsburgh, Pennsylvania
Chapter 82. Congenital Heart Disease in the Adolescent and Adult Chapter 90. Cardiovascular Disease in Older Adults

Dirk J. Duncker, MD, PhD Kenneth E. Freedland, PhD

Professor of Experimental Cardiology Professor of Psychiatry
Department of Cardiology Washington University School of Medicine in St. Louis
Erasmus MC, University Medical Center Rotterdam Saint Louis, Missouri
Rotterdam, The Netherlands Chapter 99. Psychiatric and Psychosocial Aspects of Cardiovascular Disease
Chapter 36. Coronary Blood Flow and Myocardial Ischemia
Paul Friedman, MD
Kenneth A. Ellenbogen, MD Norman Blane & Billie Jean Harty Chair
Martha M. and Harold W. Kimmerling Professor of Cardiology Mayo Clinic Department of Cardiovascular Medicine Honoring
Director, Electrophysiology and Pacing Robert L. Frye, MD
Virginia Commonwealth University School of Medicine Professor of Medicine
Richmond,Virginia Mayo Clinic College of Medicine and Science
Chapter 64. Therapy for Cardiac Arrhythmias Rochester, Minnesota
Chapter 11. Artificial Intelligence in Cardiovascular Medicine
Thomas H. Everett IV, PhD
Associate Professor of Medicine J. Michael Gaziano, MD, MPH
The Krannert Institute of Cardiology and Division of Cardiology Professor of Medicine
Indiana University School of Medicine Harvard Medical School
Indianapolis, Indiana Chief, Division of Aging
Chapter 71. Hypotension and Syncope Brigham and Women’s Hospital
Director, Preventive Cardiology
James C. Fang, MD VA Boston Healthcare System
Professor of Medicine Boston, Massachusetts
Division of Cardiovascular Medicine Chapter 2. Global Burden of Cardiovascular Disease
University of Utah
Executive Director, Cardiovascular Service Line Thomas A. Gaziano, MD, MSc
University of Utah Health Sciences Associate Professor
Salt Lake City, Utah Harvard Medical School
Chapter 13. History and Physical Examination: An Evidence-­Based Physician
Approach Cardiovascular Medicine Division
Brigham & Women’s Hospital
Boston, Massachusetts
Chapter 2. Global Burden of Cardiovascular Disease
 x
Jacques Genest, MD William J. Groh, MD, MPH
Professor of Medicine Clinical Professor of Medicine
Faculty of Medicine Medical University of South Carolina
CONTRIBUTORS

McGill University Chief of Medicine

Research Institute of the McGill University Health Centre Ralph H. Johnson VAMC
Montreal, Quebec, Canada Charleston, South Carolina
Chapter 27. Lipoprotein Disorders and Cardiovascular Disease Chapter 100. Neuromuscular Disorders and Cardiovascular Disease

Robert Gerszten, MD Martha Gulati, MD, MS

Herman Dana Professor of Medicine Chief of Cardiology
Harvard Medical School Professor of Medicine
Chief, Division of Cardiovascular Medicine University of Arizona–Phoenix
Beth Israel Deaconess Medical Center Phoenix, Arizona
Boston, Massachusetts Chapter 91. Cardiovascular Disease in Women
Chapter 8. Proteomics and Metabolomics in Cardiovascular Medicine
Rebecca Tung Hahn, MD
Linda D. Gillam, MD, MPH Director of Interventional Echocardiography
Dorothy and Lloyd Huck Chair Center for Interventional and Vascular Therapy
Department of Cardiovascular Medicine Columbia University Medical Center
Morristown Medical Center New York, New York
Morristown, New Jersey; Chapter 76. Mitral Regurgitation
Professor of Medicine
Thomas Jefferson University Gerd Hasenfuss, MD
Philadelphia, Pennsylvania Professor of Medicine
Chapter 16. Echocardiography Chair, Department of Cardiology and Pneumology
University of Göttingen Medical Center
John R. Giudicessi, MD, PhD Göttingen, Germany
Assistant Professor of Medicine Chapter 47. Pathophysiology of Heart Failure
Department of Cardiovascular Medicine (Division of Heart Rhythm
Services and the Windland Smith Rice Genetic Heart Rhythm Howard C. Herrmann, MD
Clinic) John W. Bryfogle Jr. Professor of Cardiovascular Medicine
Mayo Clinic College of Medicine and Science Division of Cardiovascular Medicine
Rochester, Minnesota University of Pennsylvania Perelman School of Medicine
Chapter 63. Genetics of Cardiac Arrhythmias Health System Director for Interventional Cardiology
Hospital of the University of Pennsylvania
Robert P. Giugliano, MD, SM Philadelphia, Pennsylvania
Staff Physician Chapter 78. Transcatheter Therapies for Mitral and Tricuspid Valvular
Cardiovascular Medicine Heart Disease
Brigham and Women’s Hospital
Professor of Medicine Joerg Herrmann, MD
Harvard Medical School Professor of Medicine
Boston, Massachusetts Department of Cardiovascular Medicine
Chapter 39. Non-­ST Elevation Acute Coronary Syndromes Mayo Clinic
Rochester, Minnesota
Ary L. Goldberger, MD Chapter 22. Invasive Hemodynamic Diagnosis of Cardiac Disease
Professor of Medicine Chapter 57. Cardio-­Oncology: Approach to the Patient
Harvard Medical School
Department of Medicine Ray E. Hershberger, MD
Beth Israel Deaconess Medical Center Professor of Internal Medicine
Boston, Massachusetts Director, Division of Human Genetics
Chapter 14. Electrocardiography Division of Cardiovascular Medicine
Section of Heart Failure and Cardiac Transplantation
Jeffrey J. Goldberger, MD, MBA Dorothy M. Davis Heart and Lung Research Institute
Professor of Medicine Wexner Medical Center at the Ohio State University
Chief, Cardiovascular Division Columbus, Ohio
University of Miami Miller School of Medicine Chapter 52. The Dilated, Restrictive, and Infiltrative Cardiomyopathies
Miami, Florida
Chapter 70. Cardiac Arrest and Sudden Cardiac Death Carolyn Y. Ho, MD
Associate Professor of Medicine
Samuel Z. Goldhaber, MD Cardiovascular Division
Professor of Medicine Brigham and Women’s Hospital
Harvard Medical School Boston, Massachusetts
Director, Thrombosis Research Group Chapter 54. Hypertrophic Cardiomyopathy
Associate Chief and Clinical Director
Division of Cardiovascular Medicine Priscilla Y. Hsue, MD
Brigham and Women’s Hospital Professor
Boston, Massachusetts Department of Medicine
Chapter 87. Pulmonary Embolism and Deep Vein Thrombosis University of California, San Francisco
San Francisco, California
Chapter 85. Cardiovascular Abnormalities in HIV-­Infected Individuals
 xi
W. Gregory Hundley, MD Scott Kinlay, MBBS, PhD
Professor of Medicine Chief, Cardiology (acting)
Chairman, Cardiology Division Director Cardiac Catheterization Laboratory and Vascular Medicine

Contributors
VCU School of Medicine VA Boston Healthcare System
Director, Pauley Heart Center West Roxbury, Massachusetts
Virginia Commonwealth University Health Physician, Cardiovascular Division
Richmond,Virginia Brigham and Women’s Hospital
Chapter 98. Tumors Affecting the Cardiovascular System Associate Professor in Medicine
Harvard Medical School
Silvio E. Inzucchi, MD Adjunct Associate Professor in Medicine
Professor, Internal Medicine (Endocrinology) Boston University Medical School
Yale University School of Medicine Boston, Massachusetts
Clinical Chief, Endocrinology Chapter 44. Treatment of Noncoronary Obstructive Vascular Disease
Director,Yale Diabetes Center
Yale-­New Haven Hospital Allan L. Klein, MD, FRCP(C)
New Haven, Connecticut Professor of Medicine
Chapter 31. Diabetes and the Cardiovascular System Cleveland Clinic Lerner College of Medicine of Case Western Reserve
University
Francine L. Jacobson, MD, MPH Director, Center for the Diagnosis and Treatment of Pericardial
Thoracic Radiologist Diseases
Brigham and Women’s Hospital Department of Cardiovascular Medicine
Harvard Medical School Heart,Vascular and Thoracic Institute
Boston, Massachusetts Cleveland Clinic
Chapter 17. Chest Radiography in Cardiovascular Disease Cleveland, Ohio
Chapter 86. Pericardial Diseases
James L. Januzzi Jr., MD
Physician Robert A. Kloner, MD, PhD
Cardiology Division Professor of Medicine (Clinical Scholar)
Massachusetts General Hospital Cardiovascular Division
Hutter Family Professor of Medicine Keck School of Medicine of University of Southern California
Harvard Medical School Los Angeles, California;
Boston, Massachusetts Chief Science Officer
Chapter 48. Approach to the Patient with Heart Failure Scientific Director of Cardiovascular Research Institute
Huntington Medical Research Institutes
Karen E. Joynt Maddox, MD, MPH Pasadena, California
Associate Professor of Medicine Chapter 84. Cardiomyopathies Induced by Drugs or Toxins
Cardiovascular Division
Washington University School of Medicine in St. Louis Kirk U. Knowlton, MD
Co-­Director, Center for Health Economics and Policy Director of Cardiovascular Research
Institute for Public Health at Washington University Intermountain Healthcare Heart Institute
Saint Louis, Missouri Adjunct Professor
Chapter 6. Impact of Health Care Policy on Quality, Outcomes, and Department of Medicine
Equity in Cardiovascular Disease University of Utah
Salt Lake City, Utah;
Jonathan M. Kalman, MBBS, PhD Professor Emeritus of Medicine
Director of Cardiac Electrophysiology University of California, San Diego
Department of Cardiology La Jolla, California
Royal Melbourne Hospital, Melbourne Chapter 55. Myocarditis
Professor of Medicine
University of Melbourne Eric V. Krieger, MD
Melbourne,Victoria, Australia Professor of Medicine
Chapter 65. Supraventricular Tachycardias Division of Cardiology
University of Washington School of Medicine
Suraj Kapa, MD Director, Adult Congenital Heart Service
Assistant Professor of Medicine University of Washington Medical Center
Cardiovascular Diseases Seattle Children’s Hospital
Mayo Clinic College of Medicine and Science Seattle, Washington
Rochester, Minnesota Chapter 82. Congenital Heart Disease in the Adolescent and Adult
Chapter 11. Artificial Intelligence in Cardiovascular Medicine
Harlan M. Krumholz, MD, SM
Morton J. Kern, MD Harold H. Hines, Jr. Professor of Medicine
Professor of Medicine Section of Cardiovascular Medicine
University California, Irvine Department of Medicine
Orange, California; Department of Health Policy and Management
Chief of Medicine and Cardiology School of Public Health
Veterans Administration Long Beach Healthcare System Yale School of Medicine
Long Beach, California Center for Outcomes Research and Evaluation
Chapter 22. Invasive Hemodynamic Diagnosis of Cardiac Disease Yale New Haven Hospital
New Haven, Connecticut
Chapter 5. Clinical Decision-­Making in Cardiology
 xii
Dharam J. Kumbhani, MD, SM Martin B. Leon, MD
Associate Professor of Medicine The Mallah Family Professor of Cardiology
Section Chief, Interventional Cardiology Director, Center for Interventional Vascular Therapy
CONTRIBUTORS

Department of Internal Medicine Columbia University Irving Medical Center

University of Texas Southwestern Medical Center NY Presbyterian Hospital
Dallas, Texas Founder and Chairman Emeritus
Chapter 41. Percutaneous Coronary Intervention Cardiovascular Research Foundation
New York, New York
Raymond Y. Kwong, MD, MPH Chapter 74. Transcatheter Aortic Valve Replacement
Professor of Medicine
Harvard Medical School Martin M. LeWinter, MD
Director of Cardiac Magnetic Resonance Imaging Professor Emeritus of Medicine and Molecular Physiology and
Cardiovascular Division Biophysics
Brigham and Women’s Hospital Larner College of Medicine at the University of Vermont
Boston, Massachusetts Attending Cardiologist
Chapter 19. Cardiovascular Magnetic Resonance Imaging University of Vermont Medical Center
Burlington,Vermont
Bonnie Ky, MD, MSCE Chapter 86. Pericardial Diseases
Associate Professor of Medicine and Epidemiology
Division of Cardiovascular Medicine Peter Libby, MD
Senior Scholar Mallinckrodt Professor of Medicine
Department of Biostatistics, Epidemiology and Informatics Harvard Medical School
University of Pennsylvania School of Medicine Brigham and Women’s Hospital
Philadelphia, Pennsylvania Boston, Massachusetts
Chapter 56. Cardio-­Oncology: Managing Cardiotoxic Effects of Cancer Chapter 10. Biomarkers and Use in Precision Medicine
Therapies Chapter 24. The Vascular Biology of Atherosclerosis
Chapter 25. Primary Prevention of Cardiovascular Disease
Carolyn S.P. Lam, MBBS, PhD, MRCP, MS Chapter 27. Lipoprotein Disorders and Cardiovascular Disease
Professor Chapter 37. ST-­Elevation Myocardial Infarction: Pathophysiology and
Cardiovascular Academic Clinical Program Clinical Evolution
Duke–National University of Singapore
Senior Consultant Cardiologist JoAnn Lindenfeld, MD
National Heart Centre Singapore Professor of Medicine
Singapore Samuel S Riven MD Directorship in Cardiology
Chapter 51. Heart Failure with Preserved and Mildly Reduced Ejection Vanderbilt University Medical Center
Fraction Nashville, Tennessee
Chapter 58. Devices for Monitoring and Managing Heart Failure
Eric Larose, DVM, MD, FRCPC
Professor and Head of Cardiology Division Brian R. Lindman, MD, MSc
Department of Medicine Associate Professor of Medicine
Chair of Research & Innovation in Cardiovascular Imaging Medical Director, Structural Heart and Valve Center
Université Laval Cardiovascular Division
Cardiologist, Institut universitaire de cardiologie et de pneumologie Vanderbilt University Medical Center
de Québec – Université Laval Nashville, Tennessee
Quebec City, Quebec, Canada Chapter 72. Aortic Valve Stenosis
Chapter 30. Obesity: Medical and Surgical Management
Michael J. Mack, MD
John M. Lasala, MD, PhD Chair, Cardiovascular Service Line
Professor of Medicine Baylor Scott & White Health
Director, Structural Heart Disease Program President, Baylor Scott & White Research Institute
Cardiology Division Dallas, Texas
Washington University School of Medicine in St. Louis Chapter 74. Transcatheter Aortic Valve Replacement
Saint Louis, Missouri
Chapter 83. Catheter-­Based Treatment of Congenital Heart Disease in Mohammad Madjid, MD, MS
Adults Associate Professor of Medicine
McGovern Medical School
Daniel J. Lenihan, MD University of Texas Health Science Center at Houston
President, International Cardio-Oncology Society Interventional Cardiologist
Professor of Medicine Heart and Vascular Institute
Director, Cardio-­Oncology Center of Excellence Memorial Hermann Hospital
Cardiovascular Division Houston, Texas
Washington University School of Medicine in St. Louis Chapter 94. Endemic and Pandemic Viral Illnesses and Cardiovascular
Saint Louis, Missouri Disease: Influenza and COVID-­19
Chapter 98. Tumors Affecting the Cardiovascular System
Douglas L. Mann, MD
Eric J. Lenze, MD Lewin Distinguished Professor of Cardiovascular Disease
Professor of Psychiatry Washington University School of Medicine
Washington University School of Medicine in St. Louis Saint Louis, Missouri
Saint Louis, Missouri Chapter 47. Pathophysiology of Heart Failure
Chapter 99. Psychiatric and Psychosocial Aspects of Cardiovascular Chapter 48. Approach to the Patient With Heart Failure
Disease Chapter 50. Management of Heart Failure Patients with Reduced
Ejection Fraction
 xiii
Bradley A. Maron, MD Roxana Mehran, MD
Associate Professor of Medicine Professor of Medicine (Cardiology)
Division of Cardiovascular Medicine Director of Interventional Cardiovascular Research and Clinical Trials

Contributors
Brigham and Women’s Hospital Zena and Michael A. Wiener Cardiovascular Institute
Harvard Medical School Icahn School of Medicine at Mount Sinai
Department of Cardiology New York, New York
Boston VA Healthcare System Chapter 21. Coronary Angiography and Intravascular Imaging
Boston, Massachusetts
Chapter 88. Pulmonary Hypertension John M. Miller, MD
Professor of Medicine
Nikolaus Marx, MD Indiana University School of Medicine
Professor of Medicine / Cardiology Director, Cardiac Electrophysiology Services
Head of the Department of Internal Medicine I Indiana University Health
University Hospital Aachen Indianapolis, Indiana
Aachen, Germany Chapter 64. Therapy for Cardiac Arrhythmias
Chapter 31. Diabetes and the Cardiovascular System
David M. Mirvis, MD
Justin C. Mason, PhD, FRCP Professor Emeritus
Professor of Vascular Rheumatology Preventive Medicine
Vascular Sciences and Rheumatology University of Tennessee College of Medicine
Imperial College London Memphis, Tennessee
London, United Kingdom Chapter 14. Electrocardiography
Chapter 97. Rheumatic Diseases and the Cardiovascular System
Ana Olga Mocumbi, MD, PhD
Mathew S. Maurer, MD Associate Professor
Arnold and Arlene Goldstein Professor of Cardiology Internal Medicine
Professor of Medicine Universidade Eduardo Mondlane
Columbia University College of Physicians and Surgeons Head of Division
Center for Advanced Cardiac Care Non Communicable Diseases
Columbia University Medical Center Instituto Nacional de Saúde
Director, Clinical Cardiovascular Research Laboratory for the Elderly Maputo, Mozambique
New York, New York Chapter 81. Rheumatic Fever
Chapter 53. Cardiac Amyloidosis
Samia Mora, MD
Peter A. McCullough, MD, MPH Associate Professor of Medicine
Consultant Cardiologist Harvard Medical School
Clinical Professor of Medicine Associate Physician
Department of Internal Medicine Brigham and Women’s Hospital
Texas A&M College of Medicine Boston, Massachusetts
Dallas, Texas Chapter 25. Primary Prevention of Cardiovascular Disease
Chapter 101. Interface Between Renal Disease and Cardiovascular Chapter 27. Lipoprotein Disorders and Cardiovascular Disease
Illness
Fred Morady, MD
Darren K. McGuire, MD, MHSc McKay Professor of Cardiovascular Disease
Professor, Internal Medicine Department of Medicine
Division of Cardiology University of Michigan
University of Texas Southwestern Medical Center Ann Arbor, Michigan
Dallas, Texas Chapter 66. Atrial Fibrillation: Clinical Features, Mechanisms, and
Chapter 31. Diabetes and the Cardiovascular System Management

Alanna A. Morris, MD, MSc

John McMurray, OBE BSc (Hons), MB ChB (Hons), MD,
Associate Professor of Medicine
FRCP
Director, Heart Failure Research
Professor of Medical Cardiology
Emory University School of Medicine
Deputy-­Director (Clinical), Institute of Cardiovascular and Medical
Atlanta, Georgia
Sciences
Chapter 93. Heart Disease in Racially and Ethnically Diverse Populations
BHF Cardiovascular Research Centre
University of Glasgow David A. Morrow, MD, MPH
Honorary Consultant Cardiologist Professor of Medicine
Queen Elizabeth University Hospital Harvard Medical School
Glasgow, Scotland, United Kingdom Boston, Massachusetts
Chapter 4. Clinical Trials in Cardiovascular Medicine Chapter 37. ST-­Elevation Myocardial Infarction: Pathophysiology and
Clinical Evolution
Elizabeth M. McNally, MD, PhD Chapter 38. ST-­Elevation Myocardial Infarction: Management
Director, Center for Genetic Medicine Chapter 40. Stable Ischemic Heart Disease
Northwestern University Feinberg School of Medicine
Chicago, Illinois Dariush Mozaffarian, MD, DrPH
Chapter 100. Neuromuscular Disorders and Cardiovascular Disease Dean, Friedman School of Nutrition Science & Policy
Jean Mayer Professor of Nutrition
Tufts University School of Medicine
Boston, Massachusetts
Chapter 29. Nutrition and Cardiovascular and Metabolic Diseases
 xiv
Kiran Musunuru, MD, PhD, MPH, ML Jeffrey E. Olgin, MD
Professor of Cardiovascular Medicine and Genetics Gallo-­Chatterjee Distinguished Professor
Cardiovascular Institute Chief, Division of Cardiology
CONTRIBUTORS

University of Pennsylvania Perelman School of Medicine University of California, San Francisco

Philadelphia, Pennsylvania San Francisco, California
Chapter 7. Applications of Genetics to Cardiovascular Medicine Chapter 68. Bradyarrhythmias and Atrioventricular Block

Robert J. Myerburg, MD Steve R. Ommen, MD

Professor of Medicine and Physiology Division of Cardiovascular Diseases
Department of Medicine Mayo Clinic College of Medicine and Science
University of Miami Miller School of Medicine Rochester, Minnesota
Miami, Florida Chapter 54. Hypertrophic Cardiomyopathy
Chapter 70. Cardiac Arrest and Sudden Cardiac Death
Catherine M. Otto, MD
Pradeep Natarajan, MD, MMSc Professor of Medicine
Director of Preventive Cardiology J. Ward Kennedy-­Hamilton Endowed Chair in Cardiology
Massachusetts General Hospital Division of Cardiology
Assistant Professor of Medicine University of Washington School of Medicine
Harvard Medical School Director, Heart Valve Clinic
Boston, Massachusetts; Associate Director, Echocardiography
Associate Member University of Washington Medical Center
Program in Medical and Population Genetics Seattle, Washington
Broad Institute of Harvard and MIT Chapter 72. Aortic Valve Stenosis
Cambridge, Massachusetts
Chapter 7. Applications of Genetics to Cardiovascular Medicine Francis D. Pagani, MD, PhD
Otto Gago MD Endowed Professor of Cardiac Surgery
Stanley Nattel, MDCM Department of Cardiac Surgery
Professor University of Michigan
Department of Medicine Ann Arbor, Michigan
Paul-­David Chair in Cardiovascular Electrophysiology Chapter 59. Mechanical Circulatory Support
Montreal Heart Institute
University of Montreal Kristen K. Patton, MD
Montreal, Quebec, Canada Professor of Medicine
Chapter 62. Mechanisms of Cardiac Arrhythmias Division of Cardiology
University of Washington
Rick A. Nishimura, MD Seattle, Washington
Judd and Mary Morris Leighton Professor of Cardiovascular Diseases Chapter 68. Bradyarrhythmias and Atrioventricular Block
Department of Cardiovascular Medicine
Mayo Clinic College of Medicine and Science Patricia A. Pellikka, MD
Rochester, Minnesota The Betty Knight Scripps Professor of Medicine
Chapter 73. Aortic Regurgitation Mayo Clinic College of Medicine and Science
Vice Chair, Academic Affairs and Faculty Development
Vuyisile T. Nkomo, MD, MPH Consultant, Department of Cardiovascular Medicine
Cardiologist Director, Ultrasound Research Center
Professor of Medicine Mayo Clinic
Department of Cardiovascular Medicine Rochester, Minnesota
Mayo Clinic College of Medicine and Science Chapter 77. Tricuspid, Pulmonic, and Multivalvular Disease
Rochester, Minnesota
Chapter 77. Tricuspid, Pulmonic, and Multivalvular Disease Gregory Piazza, MD, MS
Staff Physician
Peter Noseworthy, MD Cardiovascular Division
Consultant Department of Medicine
Cardiovascular Diseases Section Head,Vascular Medicine
Mayo Clinic College of Medicine and Science Brigham and Women’s Hospital
Rochester, Minnesota Boston, Massachusetts
Chapter 11. Artificial Intelligence in Cardiovascular Medicine Chapter 87. Pulmonary Embolism and Deep Vein Thrombosis

Patrick T. O’Gara, MD Philippe Pibarot, DVM, PhD

Professor of Medicine Professor
Harvard Medical School Department of Medicine
Senior Physician Québec Heart & Lung Institute
Cardiovascular Division Université Laval
Brigham and Women’s Hospital Québec City, Quebec, Canada
Boston, Massachusetts Chapter 79. Prosthetic Heart Valves
Chapter 13. History and Physical Examination: An Evidence-­Based
Approach
Chapter 79. Prosthetic Heart Valves
 xv
Paul Poirier, MD, PhD, FRCPC Paul M Ridker, MD, MPH
Chief, Cardiac Prevention/Rehabilitation Eugene Braunwald Professor of Medicine
Institut universitaire de cardiologie et de pneumologie de Québec – Harvard Medical School

Contributors
Université Laval Director, Center for Cardiovascular Disease Prevention
Professor Brigham and Women’s Hospital
Faculty of Pharmacy Boston, Massachusetts
Université Laval Chapter 10. Biomarkers and Use in Precision Medicine
Quebec City, Quebec, Canada Chapter 25. Primary Prevention of Cardiovascular Disease
Chapter 30. Obesity: Medical and Surgical Management
Dan M. Roden, MD
Dorairaj Prabhakaran, MD, DM (Cardiology), MSc, FRCP Professor of Medicine, Pharmacology, and Biomedical Informatics
Vice President, Research and Policy Senior Vice President for Personalized Medicine
Public Health Foundation of India Vanderbilt University School of Medicine
Executive Director, Centre for Chronic Disease Control Nashville, Tennessee
Gurgaon, Haryana, India; Chapter 9. Principles of Drug Therapeutics, Pharmacogenomics, and
Professor Biologics
Department of Epidemiology
London School of Hygiene and Tropical Medicine Frederick L. Ruberg, MD
London, United Kingdom Associate Professor of Medicine
Chapter 2. Global Burden of Cardiovascular Disease Section of Cardiovascular Medicine
Department of Medicine and Amyloidosis Center
Sanjay Rajagopalan, MD Boston Medical Center
Professor of Medicine Boston University School of Medicine
Director, Case Cardiovascular Research Institute Boston, Massachusetts
Case Western Reserve University Chapter 53. Cardiac Amyloidosis
Chief, Division of Cardiovascular Medicine
Harrington Heart and Vascular Institute Marc S. Sabatine, MD, MPH
University Hospitals Cleveland Medical Center Chair, TIMI Study Group
Cleveland, Ohio Lewis Dexter MD Distinguished Chair in Cardiovascular Medicine
Chapter 3. Impact of the Environment on Cardiovascular Health Brigham and Women’s Hospital
Professor of Medicine
Michael J. Reardon, MD Harvard Medical School
Professor of Cardiothoracic Surgery Boston, Massachusetts
Department of Cardiovascular Surgery Chapter 35. Approach to the Patient with Chest Pain
Houston Methodist Hospital
Houston, Texas Prashanthan Sanders, MBBS, PhD
Chapter 78. Transcatheter Therapies for Mitral and Tricuspid Valvular Director, Centre for Heart Rhythm Disorders
Heart Disease School of Medicine
Chapter 98. Tumors Affecting the Cardiovascular System University of Adelaide
Director, Cardiac Electrophysiology and Pacing
Susan Redline, MD, MPH Department of Cardiology
Peter C. Farrell Professor of Sleep Medicine Royal Adelaide Hospital
Harvard Medical School Director, Heart Rhythm Group
Senior Physician Heart Health
Division of Sleep and Circadian Disorders South Australian Health and Medical Research Institute
Departments of Medicine and Neurology Adelaide, Australia
Brigham and Women’s Hospital Chapter 65. Supraventricular Tachycardias
Boston, Massachusetts
Chapter 89. Sleep-­Disordered Breathing and Cardiac Disease Marc Schermerhorn, MD
George H. A. Clowes Jr. Professor of Surgery
Shereif Rezkalla, MD Harvard Medical School
Adjunct Professor of Medicine Chief, Division of Vascular and Endovascular Surgery
University of Wisconsin Beth Israel Deaconess Medical Center
Madison, Wisconsin; Boston, Massachusetts
Department of Cardiology and Cardiovascular Research Chapter 42. Diseases of the Aorta
Marshfield Clinic Health System
Marshfield, Wisconsin Benjamin M. Scirica, MD, MPH
Chapter 84. Cardiomyopathies Induced by Drugs or Toxins Associate Professor of Medicine
Harvard Medical School
Michael W. Rich, MD Senior Investigator, TIMI Study Group
Professor of Medicine Associate Physician, Cardiovascular Division
Division of Cardiology Brigham and Women’s Hospital
Washington University School of Medicine in St. Louis Boston, Massachusetts
Saint Louis, Missouri Chapter 37. ST-­Elevation Myocardial Infarction: Pathophysiology and
Chapter 90. Cardiovascular Disease in Older Adults Clinical Evolution
Chapter 99. Psychiatric and Psychosocial Aspects of Cardiovascular
Disease
 xvi
Arnold H. Seto, MD, MPA Randall C. Starling, MD, MPH
Associate Clinical Professor Professor of Medicine
University of California, Irvine Kaufman Center for Heart Failure
CONTRIBUTORS

Cardiologist Heart, Thoracic and Vascular Institute

Veterans Administration Long Beach Healthcare System Cleveland Clinic
Long Beach, California Cleveland, Ohio
Chapter 22. Invasive Hemodynamic Diagnosis of Cardiac Disease Chapter 60. Cardiac Transplantation

Sanjiv J. Shah, MD William G. Stevenson, MD

Neil Stone MD Professor of Medicine Professor of Medicine
Division of Cardiology Division of Cardiology
Northwestern University Feinberg School of Medicine Vanderbilt University Medical Center
Chicago, Illinois Nashville, Tennessee
Chapter 51. Heart Failure with Preserved and Mildly Reduced Ejection Chapter 67.Ventricular Arrhythmias
Fraction
John R. Teerlink, MD, FRCP(UK)
Shabana Shahanavaz, MBBS Professor of Medicine
Associate Professor of Pediatrics University of California School of Medicine, San Francisco,
Director, Cardiac Catheterization Laboratory Director, Heart Failure
The Heart Institute Director, Echocardiography
Cincinnati Children’s Hospital Section of Cardiology
Cincinnati, Ohio San Francisco Veteran Affairs Medical Center
Chapter 83. Catheter-­Based Treatment of Congenital Heart Disease in San Francisco, California
Adults Chapter 49. Diagnosis and Management of Acute Heart Failure

Kalyanam Shivkumar, MD, PhD David J. Tester, BS

Professor of Medicine (Cardiology), Radiology, and Bioengineering Associate Professor of Medicine
Director, UCLA Cardiac Arrhythmia Center and Electrophysiology Mayo Clinic College of Medicine and Science
Programs Department of Molecular Pharmacology & Experimental
Director, Adult Cardiac Catheterization Laboratories Therapeutics (Windland Smith Rice Sudden Death Genomics
Ronald Reagan UCLA Medical Center Laboratory)
Los Angeles, California Mayo Clinic
Chapter 102. Cardiovascular Manifestations of Autonomic Disorders Rochester, Minnesota
Chapter 63. Genetics of Cardiac Arrhythmias
Candice K. Silversides, SM, MD
Professor of Medicine Randal Jay Thomas, MD, MS
University of Toronto Pregnancy and Heart Disease Program Professor of Medicine
Toronto, Ontario, Canada Mayo Clinic Alix School of Medicine
Chapter 92. Pregnancy and Heart Disease Medical Director, Cardiac Rehabilitation Program
Division of Preventive Cardiology
Samuel C. Siu, MD, SM, MBA Department of Cardiovascular Medicine
Professor of Medicine Mayo Clinic
Division of Cardiology Rochester, Minnesota
Schulich School of Medicine and Dentistry Chapter 33. Comprehensive Cardiac Rehabilitation
Western University
London, Ontario, Canada Paul D. Thompson, MD
Chapter 92. Pregnancy and Heart Disease Chief of Cardiology, Emeritus
Hartford Hospital
Scott D. Solomon, MD Hartford, Connecticut
The Edward D. Frohlich Distinguished Chair Chapter 32. Exercise and Sports Cardiology
Professor of Medicine
Harvard Medical School Gordon F. Tomaselli, MD
Senior Physician Professor of Medicine (Cardiology)
Brigham and Women’s Hospital The Marilyn and Stanley M. Katz Dean
Boston, Massachusetts Albert Einstein College of Medicine
Chapter 4. Clinical Trials in Cardiovascular Medicine Executive Vice President and Chief Academic Officer
Chapter 16. Echocardiography Montefiore Medicine
Chapter 51. Heart Failure with Preserved and Mildly Reduced Ejection Bronx, New York
Fraction Chapter 61. Approach to the Patient with Cardiac Arrhythmias
Chapter 94. Endemic and Pandemic Viral Illnesses and Cardiovascular Chapter 62. Mechanisms of Cardiac Arrhythmias
Disease: Influenza and COVID-­19 Chapter 66. Atrial Fibrillation: Clinical Features, Mechanisms, and
Management
Matthew J. Sorrentino, MD Chapter 100. Neuromuscular Disorders and Cardiovascular Disease
Professor of Medicine
Section of Cardiology
UChicago Medicine
Chicago, Illinois
Chapter 26. Systemic Hypertension: Mechanisms, Diagnosis, and
Treatment
 xvii
Mintu P. Turakhia, MD, MAS Nanette Kass Wenger, MD
Associate Professor of Medicine (Cardiovascular Medicine) Professor of Medicine (Cardiology) Emeritus
Executive Director, Center for Digital Health Emory University School of Medicine

Contributors
Stanford University Consultant, Emory Heart and Vascular Center
Stanford, California; Atlanta, Georgia
Chief, Cardiac Electrophysiology Chapter 90. Cardiovascular Disease in Older Adults
VA Palo Alto Health Care System
Palo Alto, California Walter R. Wilson, MD
Chapter 12. Wearable Devices in Cardiovascular Medicine Professor of Medicine
Mayo Clinic College of Medicine and Science
Anne Marie Valente, MD Rochester, Minnesota
Associate Professor Chapter 80. Infectious Endocarditis and Infections of Indwelling Devices
Pediatrics and Internal Medicine
Harvard Medical School Justina C. Wu, MD, PhD
Director, Boston Adult Congenital Heart Program Assistant Professor of Medicine
Children’s Hospital Boston Harvard Medical School
Brigham and Women’s Hospital Director of Echocardiography
Boston, Massachusetts Brigham and Women’s Hospital
Chapter 82. Congenital Heart Disease in the Adolescent and Adult Boston, Massachusetts
Chapter 16. Echocardiography
Orly Vardeny, PharmD, MS
Associate Professor of Medicine Katja Zeppenfeld, MD, PhD
Center for Care Delivery and Outcomes Research Professor of Cardiology
Minneapolis VA Health Care System and University of Minnesota Leiden University Medical Centre
Minneapolis, Minnesota Leiden, The Netherlands
Chapter 94. Endemic and Pandemic Viral Illnesses and Cardiovascular Chapter 67.Ventricular Arrhythmias
Disease: Influenza and COVID-­19
Michael R. Zile, MD
David D. Waters, MD Charles Ezra Daniels Professor of Medicine
Professor Emeritus Division of Cardiology
Department of Medicine Medical University of South Carolina
University of California, San Francisco Charleston, South Carolina
San Francisco, California Chapter 58. Devices for Monitoring and Managing Heart Failure
Chapter 85. Cardiovascular Abnormalities in HIV-­Infected Individuals

Jeffrey I. Weitz, MD, FRCP(C)

Professor of Medicine and Biochemistry
McMaster University
Executive Director
Thrombosis and Atherosclerosis Research Institute
Hamilton, Ontario, Canada
Chapter 95. Hemostasis, Thrombosis, Fibrinolysis, and Cardiovascular
Disease
 Preface
The knowledge relevant to the practice of cardiology continues
to grow by leaps and bounds. Scientific and clinical advances have
occurred at such a rapid pace that clinicians often suffer information
overload. Communications about advances in cardiovascular med-
icine inundate practitioners on a seemingly minute-­to-­minute basis
through journals, mailings, text messages, newsletters, social media,
webinars, advertisements, and other electronic and print media. How
can a practitioner or trainee sift through this cacophony to discern
reliable, durable, and important information critical for practice?
This textbook of cardiovascular medicine offers a solution to this
quandary. The 12th edition of Braunwald’s Heart Disease provides a
comprehensive, carefully curated, balanced, and unbiased distilla-
tion not only of the tried and true, but especially the latest advances
in our field. This volume should serve the novice and experienced
practitioner alike. Trainees and those preparing for certification or
recertification examinations can use this text for an overall review of
contemporary cardiovascular medicine. Practitioners confronting a
particular clinical problem can consult the appropriate section of the
book on an as-­needed basis to answer the clinical question at hand
to aid on-­the-­spot clinical decision making. While not a basic science
textbook, this volume builds on Dr. Braunwald’s founding vision and
reviews fundamental pathophysiologic mechanisms to furnish a foun-
dation for informed practice where appropriate.
Cardiovascular medicine has expanded so enormously that few if
any individuals can maintain mastery of the entire scope of practice.
Sub-­specialization and even sub-­ sub-­
specialization have increased.
Yet, each of us encounters issues within these super-­specialized areas
when we care for and counsel our own patients.The palette of patients’
problems often overlaps the fine divisions our specialty has developed.
This book aims to provide a ready reference so that we can update our
knowledge with recent and authoritative information in areas of car-
diovascular medicine afield from our own primary areas of expertise.
The online content of this textbook contains additional new figures
and tables, as well as over 200 videos that add to the printed version.
Furthermore, through twice monthly online updates by Dr. Braunwald
and through Elsevier’s ClinicalKey, this textbook undergoes constant
updating. Indeed, with the addition of companion volumes, the Heart
Disease family has become a living learning system and comprehen-
sive reference.
As necessitated by evolution and progress in cardiovascular medi-
cine, in planning this 12th edition the editors have carefully reviewed
the content to reflect current knowledge. This edition has 14 totally
new chapters. For example, we have added chapters on artificial intel-
ligence in cardiology and on the use of wearables in cardiovascular
medicine. These two topics will doubtless change our practices pro-
foundly. We expect that future editions will continue to build on these
and other novel areas that will provide us with innovative tools to con-
front our patients’ problems.
We have added a new chapter,“Impact of the Environment on Cardio-
vascular Health,” as we recognize increasingly the clinical importance
of this critical interface. Another new chapter, “Cardiovascular Disease
Risk of Nicotine and Tobacco Products,” highlights the concerning
increase in smokeless tobacco use among youth. The burgeoning field
xviii
of cardio-­oncology has expanded coverage in the 12th edition, with
two chapters devoted to different aspects of this topic. Expanded cov-
erage of valvular heart disease includes a new chapter on interven-
tions for mitral and tricuspid valvulopathies, which complements an
updated chapter on percutaneous interventions for the aortic valve.
These additions acknowledge the growing role of structural heart dis-
ease interventions in tackling these conditions.
The period of planning and preparation of this 12th edition coin-
cided with the pandemic caused by SARS-­CoV-­2. We would be remiss
not to include an expanded discussion of viral heart diseases in a
new chapter, as our specialty needs to prepare for likely future viral
pandemics, as well as deal with the potentially long-­term cardiovas-
cular consequences of COVID-­19. Of course, each and every chapter
in the book has undergone extensive updating and revision to reflect
advances since the last edition. To this end, a number of chapters are
completely written de novo by new authors. Indeed, the 12th edition
boasts almost 80 new authors, reflecting our commitment to continu-
ous refreshment and review of the content.
Our field can take considerable pride in the rapid advances in both
basic and clinical investigation that this book highlights.Yet, we face a
disconnect between these advances and their application to practice.
To this end we include a new chapter, “Impact of Health Care Policy
on Quality and Outcomes of Cardiovascular Disease,” that focuses on
practical societal approaches to ensure that our patients can benefit
from the clinical and basic scientific advances in our field. Moreover,
closing gaps in offering progress in cardiovascular medicine to racially,
ethnically, geographically diverse, or underserved populations presents
a global challenge. We focus on cardiovascular conditions in partic-
ular segments of the population—women, people with diabetes, and
those with HIV/AIDS—that may require specialized approaches; each
of these and others have been accorded a separate chapter.The global
pandemic has placed disparities and inequities in health care in stark
relief, locally and globally. To address this problem, a new chapter,
“Heart Disease in Racially and Ethnically Diverse Populations,” deals
with cardiovascular conditions that confront disadvantaged segments
of our population.
Finally, the Editors were fortunate to enlist Professor Eugene Braun-
wald, the founder of this textbook, to contribute an opening chapter,
“Cardiovascular Disease: Past, Present, and Future,” which shares his
vision from his uniquely broad perspective. We have striven to uphold
the standards that he set for this textbook from the first five editions
that he edited solo. We have aimed to emulate his editorial prowess
and example of refreshing every page of this textbook in each edition
to maximize its utility for all who care for patients with or at risk of
developing cardiovascular disease.
Peter Libby
Robert O. Bonow
Douglas L. Mann
Gordon F. Tomaselli
Deepak L. Bhatt
Scott D. Solomon
 Preface to the First Edition
Cardiovascular disease is the greatest scourge affecting the industri-
alized nations. As with previous scourges — bubonic plague, yellow
fever, and small pox — cardiovascular disease not only strikes down a
significant fraction of the population without warning but also causes
prolonged suffering and disability in an even larger number. In the
United States alone, despite recent encouraging declines, cardiovascu-
lar disease is still responsible for almost 1 million fatalities each year
and more than half of all deaths; almost 5 million persons afflicted with
cardiovascular disease are hospitalized each year. The cost of these
diseases in terms of human suffering and material resources is almost
incalculable.
Fortunately, research focusing on the prevention, causes, diagno-
sis, and treatment of heart disease is moving ahead rapidly. Since
the early part of the twentieth century, clinical cardiology has had
a particularly strong foundation in the basic sciences of physiol-
ogy and pharmacology. More recently, the disciplines of molecular
biology, genetics, developmental biology, biophysics, biochemistry,
experimental pathology and bioengineering have also begun to
provide critically important information about cardiac function
and malfunction.
In the past 25 years, in particular, we have witnessed an explosive
expansion of our understanding of the structure and function of the
cardiovascular system—both normal and abnormal—and of our abil-
ity to evaluate these parameters in the living patient, sometimes by
means of techniques that require penetration of the skin but also with
increasing accuracy, by noninvasive methods. Simultaneously, remark-
able progress has been made in preventing and treating cardiovascular
disease by medical and surgical means. Indeed, in the United States, a
steady reduction in mortality from cardiovascular disease during the
past decade suggests that the effective application of this increased
knowledge is beginning to prolong human life span, the most valued
resource on earth.
To provide a comprehensive, authoritative text in a field that has
become as broad and deep as cardiovascular medicine, I enlisted
the aid of a number of able colleagues. However, I hoped that my
personal involvement in the writing of about half of the book would
make it possible to minimize the fragmentation, gaps, inconsisten-
cies, organizational difficulties, and impersonal tone that sometimes
plague multiauthored texts. Although Heart Disease: A Textbook of
Cardiovascular Medicine is primarily a clinical treatise and not a
textbook of fundamental cardiovascular science, an effort has been
made to explain, in some detail, the scientific bases of cardiovascular
diseases.
To the extent that this book proves useful to those who wish to
broaden their knowledge of cardiovascular medicine and thereby aids
in the care of patients afflicted with heart disease, credit must be given
to the many talented and dedicated persons involved in its prepara-
tion. I offer my deepest appreciation to my fellow contributors for their
professional expertise, knowledge, and devoted scholarship, which has
so enriched this book. I am deeply indebted to them for their coopera-
tion and willingness to deal with a demanding editor.
Eugene Braunwald
1980
xix
 Acknowledgments

The conception and creation of this textbook of over 100 chapters and almost 2000 pages required
the expertise, assistance, and skills of many dedicated individuals. We thank the contributors who have
authored the chapters that comprise this textbook. We recognize the leadership of Ms. Dolores Meloni,
executive content strategist at Elsevier, for her guidance and assistance at all stages of the planning and
preparation of this volume. Ms. Anne Snyder, senior content development specialist, provided invaluable
and detailed assistance on a daily basis. The editors owe her a great debt of gratitude. Mr. John Casey,
senior project manager, cheerfully worked with the authors and the editors in executing the composition
and proofing of this tome and accommodating last-­minute additions and alterations to make the print
edition as accurate and up to date as possible. The editors would not have been able to produce this
book and ensure its quality without all of these contributions.
We also thank colleagues the world over who provided suggestions on how to improve Braunwald’s
Heart Disease and identified points that could use clarification. We welcome such input that will enable
us to improve this edition in subsequent printings and plan future editions to meet our readers’ needs
even better.

xx
Another random document with
no related content on Scribd:
Obliquity of Ecliptic, 16, 120
Old Red Sandstone, 34
Optimum of Climate, 127
Ordovician, 33

P.
Pajaritan, 150
Palmyra, 142
Pamirs, 77
Pampean, 100, 125
Patagonia, post-glacial, 133
Patom Highlands, 78
Peat-bog Period, 140
Penck, 49, 51
Pendulation Theory, 20
Peorian, 91
Permian, 35
Persia, 84, 142
Peru, 99
Pettersson, 134, 145
Piedmont ice-sheets, 57, 109
Piltdown Man, 161
Pithecanthropus, 160
Pliocene, 47
Pluvial periods, 71, 140
Poles, motion of, 20, 40
Pre-Cambrian Glaciation, 33
Proterozoic Glaciation, 32
Pueblo ruins, 150
Pulse of Asia, 153
Pumpelly, 84, 163
Pyrenees, 57

Q.
Quaternary Ice Age, 47

R.
Ragunda, Lake, 49
moraines, 121
Reid, 138
Retreat of the Ice, 49
Riss Glaciation, 49, 61
Riss-Wurm Interglacial, 50, 53
Rixdorf, 62
Rodgers, 133
Romania, 66
Ruwenzori, 103

S.
Sagas, 141, 146
Sahara, 74, 105
Sangamon, 90
Scania, 49
Schmidt, 53
Scotland, 57, 61, 64
Scrobicularia Zone, 130
Selsey, 58
Sequoia, 143
Shell-banks, 47, 56
Siberia, 78
Sicilian, 70
Sierra Nevada, 93, 94
Sievers, 99
Silurian, 33
Skærumhede, 63
Slugs, 115
Smith, Elliott, 159
Solar radiation, 15
South America, 97, 125, 132, 157
South Georgia, 97
South Orkneys, 114
Spitaler, 18
Spitzbergen, 80, 130
Stanovoi Mountains, 79
Steppe climate, 53
Stone rivers, 98
Submerged forests, 137
Suess, Lake, 104
Sunspots, 145
Susa, Neolithic, 163
Sven Hedin, 84
Sweden, 49, 56, 118
Syria, 72

T.
Tapes, 129
Tasmania, 109
Tchad, 106
Tertiary, 42, 116
Thracia Zone, 131
Tian-Shan Mountains, 77
Tibet, 82
Tidal friction, 39
Tide-generating force, 134, 145
Tierra del Fuego, 97, 133
Tillite, 32
Titicaca, Lake, 101
Toronto Stage, 91
Trapa, 129
Trasimeno, Lake, 154
Tree-rings and rainfall, 143
Turbarian, 140
Triassic, 37
Tyndall, 19

U.
Uinta Mountains, 94
Unio in Niagara, 132
Ural Mountains, 57

V.
Venezuela, 100
Verkhoiansk Mountains, 79
Victoria Nyanza, 104
Vikings, 164
Volcanic dust, 16, 20
Vollossovitsch, 79

W.
Wales, 57, 64
Warren, Lake, 123
Wasatch Mountains, 93, 94
Wayland, 104
Wegener, 20, 34
Wernert, 53
White Sea, 130
Wine harvest, 155
Winters, severe, 155
Wisconsin Glaciation, 91, 92
Wolf, 145
Wurm Glaciation, 48

Y.
Yarmouth Stage, 88
Yoldia Sea, 50, 124
Yucatan, 151
Yukon, 124

Printed in Great Britain by Jarrold & Sons, Ltd., Norwich.

 FOOTNOTES:
[1] By this term we shall in future understand only that part of it
which is responsible for thermal effects.
[2] If the figure of the earth is adjusted to its speed of rotation
before the development of ice-sheets, the latter renders it too
prolate, and there will be a tendency for readjustment by the
transference of mass towards the equator.
[3] This has been the subject of much discussion recently. For a
summary see Science Progress, 17, 1922, October, p. 233.
[4] Leverett, F. (see Bibliography).
[5] See reference to Antevs in this connexion.
[6] “The pulse of Asia,” p. 356. See also a new work by E.
Huntington, entitled: “Climatic changes.”
[7] “Climatic variations in historic and prehistoric time.”
[8] “Sur le prétendu changement du climat européen en temps
historique.”
[9] Or lemur-like ancestor. There is evidence to show that man’s
ancestor was a nocturnal animal, whose food supply was
governed by the phases of the moon.
[10] “Scientific monthly,” New York, 4, 1917, pp. 16-26.
[11] “Science progress,” 15, 1920, p. 74.
[12] “Climate and evolution.”
[13] “Civilization and climate.”
TRANSCRIBER’S NOTE
Obvious typographical errors and punctuation errors have been corrected after
careful comparison with other occurrences within the text and consultation of
external sources.
Some hyphens in words have been silently removed, some added, when a
predominant preference was found in the original book.
Except for those changes noted below, all misspellings in the text, and
inconsistent or archaic usage, have been retained.
Pg 64: ‘powerful conviction’ replaced by ‘powerful convection.
Pg 97: ‘and Tierra del Fuega’ replaced by ‘and Tierra del Fuego’.
Pg 103: ‘Drakenberge Mountains’ replaced by ‘Drakensberg Mountains’.
Pg 150: ‘modern Pueblas who’ replaced by ‘modern Pueblos who’.
Pg 166: ‘coffiecients are’ replaced by ‘coefficients are’.
 *** END OF THE PROJECT GUTENBERG EBOOK THE
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