Mayo clinic cardiology

Mayo Clinic Cardiology
Concise Textbook
THIRD EDITION

Editors
Joseph G. Murphy, MD
Margaret A. Lloyd, MD
Associate Editors
Gregory W. Barsness, MD
Arshad Jahangir, MD
Garvan C. Kane, MD
Lyle J. Olson, MD
MAYO CLINIC SCIENTIFIC PRESS
AND INFORMA HEALTHCARE USA, INC.
Mayo Clinic Cardiology
Concise Textbook
THIRD EDITION

ISBN 0-8493-9057-5
The triple-shield Mayo logo and the words MAYO, MAYO CLINIC,
and MAYO CLINIC SCIENTIFIC PRESS are marks of Mayo Foundation
for Medical Education and Research.
©2007 by Mayo Foundation for Medical Education and Research.
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tion. This book should not be relied on apart from the advice of a qual-
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The authors, editors, and publisher have exerted efforts to ensure that
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rent recommendations and practice at the time of publication. However,
in view of ongoing research, changes in government regulations, and the
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Some drugs and medical devices presented in this publication have
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Printed in Canada
10 9 8 7 6 5 4 3 2

DEDICATION
This book is dedicated to my parents, my wife Marian,
without whose support and encouragement this textbook would not have been possible,
and my children Owen, Sinéad, and Aidan, as well as Tornados, Spartans, Pink Panthers, and Tommies everywhere.
For my parents, who taught me to love books. Booksellers everywhere, thank you as well.
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vii
FOREWORD
It is a distinct honor and pleasure to write this foreword for the third edition of Mayo Clinic Cardiology: Concise Textbook.
I have had the pleasure of working on the staff of Mayo Clinic’s Division of Cardiovascular Diseases for the past 25 years. Although the
diagnosis and treatment of cardiovascular diseases and the day-to-day practice of medicine have changed greatly during that time, the Mayo Clinic
tradition of clinical excellence in cardiovascular disease has not. The unique strength of the Division is its breadth of clinical expertise across the areas
of acute coronary care, electrophysiology, intervention, adult congenital heart disease, valvular heart disease, vascular disease, heart failure, and
others. This expertise covers both common conditions in the practice of cardiovascular disease and those that are very uncommon, even in major
tertiary referral centers. The breadth of that expertise is reflected in the range of topics covered in this book. The common conditions include ST-
segment elevation myocardial infarction, for which Mayo Clinic conducted one of the first clinical trials comparing thrombolytic therapy with
acute angioplasty, and chronic mitral insufficiency, to which Mayo Clinic investigators have made multiple major contributions to both diagnosis
and the timing and benefit of mitral valve repair. The uncommon conditions include adult congenital heart disease, hypertrophic cardiomyopathy,
and pericardial disease, on which the size of our practice has permitted a few of my colleagues to focus their expertise.
This book began as an outgrowth of the syllabus for the Mayo Cardiovascular Review Course for Cardiology Boards and Recertification. This
highly successful course attracts an annual attendance of more than 700, including cardiology fellows preparing for their initial boards, practicing
cardiologists preparing for recertification, and experienced clinicians who simply want to ensure that they are up-to-date on the latest cardiovascular
science and care. Readers from any one of these broad categories will find this book very useful.
Both the education of cardiology fellows and the practice of cardiovascular medicine are increasingly subject to time constraints. Our fellows
complain that 3 or 4 years is simply inadequate to master the rapidly expanding scope of cardiovascular science and practice. Practicing physicians
find that their working day grows ever longer, leaving less time for continuing medical education. The strength of this book is its concise presentation
of the existing state of cardiovascular practice, as emphasized by its subtitle.
There is a growing crisis in the health care system, focused on rapid increases in health care costs and evidence of suboptimal quality. The
practice of cardiovascular medicine will be under increasing pressure to shift from the more-care-is-better paradigm that dominated in the past to
afocusonimprovingqualityandefficiency.TheDartmouthAtlasofHealthCareidentifiedtheMedicarereferralregioncenteredonRochester,Minnesota,
as a “high-quality, low-cost” region. The principles underlying that efficiency are evident throughout this text. It is hoped that it will assist the read-
er in his or her personal quest to improve the quality of cardiovascular care in clinical practice.
Raymond J. Gibbons, MD
Consultant, Division of Cardiovascular Diseases
Mayo Clinic
Arthur M. & Gladys D. Gray Professor of Medicine
Mayo Clinic College of Medicine
Rochester, Minnesota

PREFACE
he cover art of the “iceberg” heart is meant to symbolize the significant extent of occult cardiovascular disease in our society and the ruthless “icy”
nature of cardiovascular death that curses the sea of humanity.
It has been a great honor to oversee the publication of this, the third, edition of Mayo Clinic Cardiology: Concise Textbook (formerly titled
Mayo Clinic Cardiology Review). Large textbooks are never the work of one or two individuals but rather the product of a team of dedicated pro-
fessionals, as has been the case for this book. This textbook from a single institution was written by a diverse faculty of more than 100 cardiologists
from more than 17 countries.
This textbook is primarily a teaching and learning textbook of cardiology rather than a reference textbook. In response to welcome feedback
from readers of our two previous textbook editions, we have maintained a relatively large typeface to make the textbook easily readable and have
avoided the temptation to reduce the font size to increase content. Newer electronic search modalities have made textbook references less timely
and we have deleted most chapter references and all multiple-choice questions to save space.
This textbook is designed to present the field of cardiology in a reader-friendly format that can be read in about 12 months. Many small car-
diology textbooks are bare-bones compilations of facts that do not explain the fundamental concepts of cardiovascular disease, and many large car-
diology textbooks are voluminous and describe cardiology in great detail. Mayo Clinic Cardiology: Concise Textbook is designed to be a bridge
between these approaches. We sought to present a solid framework of ideas with sufficient depth to make the matter interesting yet concise, aimed
specifically toward fellows in training or practicing clinicians wanting to update their knowledge. The book contains 1,400 figures, 483 of which
are color photographs to supplement the text. Teaching points and clinical pearls have been added to make the textbook come alive and challenge
the reader.
The concept for this textbook originated from the first syllabus for the Mayo Cardiovascular Review Course, a function the textbook continues
to fulfill. The impetus to produce this textbook owes much to the encouragement of Rick Nishimura, MD, and Steve Ommen, MD, the direc-
tors of the Mayo Cardiovascular Review Course now in its 11th year.
This third edition is a complete revision of all previous chapters of the textbook and has been expanded at the suggestion of cardiology fellows
to now include 40 new chapters, including newer aspects of electrophysiology, interventional cardiology, noninvasive imaging, and randomized
clinical trials.
The text is intended primarily for cardiology fellows studying for cardiology board certification and practicing cardiologists studying for board
recertification. It will also be useful for physicians studying for examinations of the Royal Colleges of Physicians, anesthesiologists, critical care
physicians, internists and general physicians with a special interest in cardiology, and coronary care and critical care nurses.
WethankallourcolleaguesintheMayoClinicDivisionofCardiovascularDiseasesatRochester,Arizona,andJacksonvillewhogenerouslycon-
tributedtothiswork.WealsothankWilliamD.Edwards,MD,forpermissiontouseslidesfromtheMayoCliniccardiologypathologicimagedata-
base.LeAnnSteeandRandallJ.Fritz,DVM,atMayoClinic,contributedenormouslythroughtheireditorialguidance.SandyBebermanatInforma
Healthcare patiently guided this project through countless tribulations. We thank both Mayo Clinic and the Informa Healthcare production teams:
at Mayo—Roberta Schwartz (production editor), Sharon Wadleigh (scientific publications specialist), Jane Craig and Virginia Dunt (editorial assis-
tants), Kenna Atherton and John Hedlund (proofreaders), Karen Barrie (art director), Jonathan Goebel (graphic designer) and Charlene Wibben
(ContinuingMedicalEducation);atInformaHealthcare—SuzanneLassandro(projecteditor),andRickBeardsley(productionandmanufacturing).
We specifically acknowledge colleagues from outside North America who contributed many ideas to this book and who translated previous editions
ofthebookintoseveralforeignlanguages.WehaveincludedashortSIconversiontableforcommonlaboratoryvaluestoaidtheirreadingofthebook.
We would appreciate comments from our readers about how we might improve this textbook or, specifically, about any errors that you find.
Joseph G. Murphy, MD Margaret A. Lloyd, MD
Consultant, Division of Cardiovascular Consultant, Division of Cardiovascular Diseases,
Diseases, and Chair, Section of Scientific Publications, Mayo Clinic
Mayo Clinic Assistant Professor of Medicine
Professor of Medicine Mayo Clinic College of Medicine
Mayo Clinic College of Medicine Rochester, Minnesota
Rochester, Minnesota
murphy.joseph@mayo.edu
T
ix

xi
SI UNITS AND ALTERNATIVE SCIENTIFIC NAMES
SI UNITS
Cholesterol (Total Cholesterol, LDL Cholesterol, HDL Cholesterol)
200 mg/dL = 5.2 mmol/L
Triglycerides
Glucose
200 mg/dL = 11.0 mmol/L
Creatinine
1 mg/dL = 88.4 μmol/L
2 mg/dL = 177 μmol/L
3 mg/dL = 265 μmol/L
ALTERNATIVE SCIENTIFIC NAMES
Epinephrine = adrenaline
Norepinephrine = noradrenaline
Isoproterenol = isoprenaline

Michael J. Ackerman, MD, PhD
Consultant, Divisions of Cardiovascular Diseases and Pediatric
Cardiology and Department of Molecular Pharmacology and
Experimental Therapeutics*
Associate Professor of Medicine, Pediatrics, and Pharmacology†
Thomas G. Allison, PhD
Consultant, Division of Cardiovascular Diseases*
Associate Professor of Medicine†
Naser M. Ammash, MD
Nandan S. Anavekar, MB, BCh
Chief Medical Resident and Instructor in Medicine†
Christopher P. Appleton, MD
Consultant, Division of Cardiovascular Diseases‡
Professor of Medicine†
Samuel J. Asirvatham, MD
John W. Askew III, MD
Fellow in Nuclear Cardiology†
Luciano Babuin, MD
Research Collaborator, Mayo School of Graduate Medical
Education†
Assistant Professor of Medicine†
Malcolm R. Bell, MD
Patricia J. M. Best, MD
Senior Associate Consultant, Division of Cardiovascular
Diseases*
Joseph L. Blackshear, MD
Consultant, Division of Cardiovascular Diseases§
David J. Bradley, MD, PhD
Peter A. Brady, MD
Jerome F. Breen, MD
Consultant, Department of Radiology*
Assistant Professor of Radiology†
John F. Bresnahan, MD
Frank V. Brozovich, MD, PhD
Diseases and Department of Physiology and Biomedical
Engineering*
Professor of Medicine and of Physiology†
T. Jared Bunch, MD
Fellow in Cardiovascular Diseases and Assistant Professor of
Medicine†
John C. Burnett, Jr, MD
Professor of Medicine and of Physiology†
Mark J. Callahan, MD
Yong-Mei Cha, MD
Krishnaswamy Chandrasekaran, MD
Panithaya Chareonthaitawee, MD
Frank C. Chen, MD
Fellow in Cardiovascular Diseases†
Horng H. Chen, MD
Stuart D. Christenson, MD
Senior Associate Consultant, Division of
Cardiovascular Diseases*
Alfredo L. Clavell, MD
Heidi M. Connolly, MD
CONTRIBUTORS
*Mayo Clinic, Rochester, Minnesota.
†Mayo Clinic College of Medicine, Rochester, Minnesota.
‡Mayo Clinic, Scottsdale, Arizona.
§Mayo Clinic, Jacksonville, Florida. xiii

Leslie T. Cooper, Jr, MD
Richard C. Daly, MD
Consultant, Division of Cardiovascular Surgery*
Associate Professor of Surgery†
Brooks S. Edwards, MD
Robert P. Frantz, MD
Paul A. Friedman, MD
Robert L. Frye, MD
Apoor S. Gami, MD
Fellow in Cardiovascular Diseases and
Gerald T. Gau, MD
Thomas C. Gerber, MD, PhD
Consultant, Division of Cardiovascular Diseases and
Department of Radiology§
Associate Professor of Medicine and of Radiology†
Bernard J. Gersh, MB, ChB, DPhil
Jason M. Golbin, DO
Fellow in Thoracic Diseases and Critical Care Medicine†
Martha A. Grogan, MD
Richard J. Gumina, MD
Senior Associate Consultant, Division of Cardiovascular Diseases*
Stephen C. Hammill, MD
David L. Hayes, MD
Chair, Division of Cardiovascular Diseases*
Sharonne N. Hayes, MD
Anthony A. Hilliard, MD
Michael J. Hogan, MD, MBA
Consultant, Division of Regional and International Medicine‡
David R. Holmes, Jr, MD
Allan S. Jaffe, MD
Arshad Jahangir, MD
Traci L. Jurrens, MD
Ravi Kanagala, MD
Diseases*
Garvan C. Kane, MD
Fellow in Cardiovascular Diseases and Instructor in Medicine†
Birgit Kantor, MD, PhD
Diseases*
Tomas Kara, MD, PhD
Research Fellow in Hypertension and Assistant Professor of
Medicine†
Bijoy K. Khandheria, MD
Chair, Division of Cardiovascular Diseases‡
Stephen L. Kopecky, MD
Iftikhar J. Kullo, MD
Sudhir S. Kushwaha, MD
André C. Lapeyre III, MD
Hon-Chi Lee, MD, PhD
§Mayo Clinic, Jacksonville, Florida. xiv

Amir Lerman, MD
Francisco Lopez-Jimenez, MD, MS
Verghese Mathew, MD
Robert D. McBane, MD
Marian T. McEvoy, MD
Consultant, Division of Dermatology*
Associate Professor of Dermatology†
Michael D. McGoon, MD
Shaji C. Menon, MD
Fellow in Pediatric Cardiology†
Fletcher A. Miller, Jr, MD
Todd D. Miller, MD
Wayne L. Miller, MD, PhD
Andrew G. Moore, MD
Instructor in Medicine†
Thomas M. Munger, MD
Ajay Nehra, MD
Consultant, Department of Urology*
Professor of Urology†
Rick A. Nishimura, MD
Jae K. Oh, MD
Lyle J. Olson, MD
Steve Ommen, MD
Oyere K. Onuma, BS
Research Trainee, Division of Cardiovascular Diseases*
Thomas A. Orszulak, MD
Professor of Surgery†
Michael J. Osborn, MD
Narith N. Ou, PharmD
Pharmacist*
Lance J. Oyen, PharmD
Pharmacist*
Assistant Professor of Pharmacy†
Douglas L. Packer, MD
John G. Park, MD
Consultant, Division of Pulmonary and Critical Care
Medicine*
Robin Patel, MD
Consultant, Division of Infectious Diseases*
Associate Professor of Microbiology and Professor of Medicine†
Patricia A. Pellikka, MD
Sabrina D. Phillips, MD
Diseases*
Co-burn J. Porter, MD
Consultant, Division of Pediatric Cardiology*
Professor of Pediatrics†
Udaya B. S. Prakash, MD
Consultant, Division of Pulmonary and Critical Care Medicine*
Professor of Medicine,†*Mayo Clinic, Rochester, Minnesota.
§Mayo Clinic, Jacksonville, Florida. xv

Abhiram Prasad, MD
Sarinya Puwanant, MD
Research Fellow in Cardiovascular Diseases†
Robert F. Rea, MD
Margaret M. Redfield, MD
Guy S. Reeder, MD
Charanjit S. Rihal, MD
Richard J. Rodeheffer, MD
Brian P. Shapiro, MD
Win-Kuang Shen, MD
Raymond C. Shields, MD
Instructor in Medicine†
Clarence Shub, MD
Justo Sierra Johnson, MD, MS
Robert D. Simari, MD
Lawrence J. Sinak, MD
Virend K. Somers, MD, PhD
Peter C. Spittell, MD
James M. Steckelberg, MD
Chair, Division of Infectious Diseases*
Thoralf M. Sundt III, MD
Professor of Surgery†
Imran S. Syed, MD
Deepak R. Talreja, MD
Fellow in Cardiovascular Diseases and Instructor in Medicine†
Zelalem Temesgen, MD
Consultant, Division of Infectious Diseases*
Andre Terzic, MD
Consultant, Department of Molecular Pharmacology*
Professor of Medicine and of Pharmacology†
Randal J. Thomas, MD, MS
Henry H. Ting, MD
Cindy W. Tom, MD
Laurence C. Torsher, MD
Consultant, Division of Anesthesia*
Assistant Professor of Anesthesiology†
Teresa S. M. Tsang, MD
Eric M. Walser, MD
Senior Associate Consultant, Department of Radiology§
Professor of Radiology†
Carole A. Warnes, MD
Paul W. Wennberg, MD
Robert Wolk, MD, PhD
Research Collaborator in Cardiovascular Diseases*
R. Scott Wright, MD
Waldemar E. Wysokinski, MD
Leonid V. Zingman, MD
Research Associate, Division of Cardiovascular Diseases*
Assistant Professor of Medicine and Instructor in Pharmacology†
§Mayo Clinic, Jacksonville, Florida. xvi

FUNDAMENTALS OF CARDIOVASCULAR DISEASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
1. Cardiovascular Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
Clarence Shub, MD
2. Applied Anatomy of the Heart and Great Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27
Joseph G. Murphy, MD, R. Scott Wright, MD
3. Evidence-Based Medicine and Statistics in Cardiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55
Apoor S. Gami, MD, Charanjit S. Rihal, MD
4. Noncardiac Surgery in Patients With Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61
Traci L. Jurrens, MD, Clarence Shub, MD
5. Essential Molecular Biology of Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .73
Cindy W. Tom, MD, Robert D. Simari, MD
6. Medical Ethics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95
John G. Park, MD
7. Restrictions on Drivers and Aircraft Pilots With Cardiac Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . .103
Stephen L. Kopecky, MD
NONINVASIVE IMAGING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115
8. Principles of Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117
Teresa S. M. Tsang, MD
9. Stress Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143
Patricia A. Pellikka, MD
10. Transesophageal Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .151
Sarinya Puwanant, MD, Lawrence J. Sinak, MD, Krishnaswamy Chandrasekaran, MD
11. Nuclear Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .161
John W. Askew III, MD, Todd D. Miller, MD
12. Positron Emission Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .173
Panithaya Chareonthaitawee, MD
13. Cardiovascular Computed Tomography and Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . .185
Thomas C. Gerber, MD, PhD, Eric M. Walser, MD
14. Cardiac Radiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .205
Jerome F. Breen, MD, Mark J. Callahan, MD
15. Atlas of Radiographs of Congenital Heart Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .223
Sabrina D. Phillips, MD, Joseph G. Murphy, MD
16. Cardiopulmonary Exercise Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .231
17. Stress Test Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .241
Stuart D. Christenson MD
xvii
TABLE OF CONTENTS

ELECTROPHYSIOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .247
18. Electrocardiographic Diagnoses: Criteria and Definitions of Abnormalities . . . . . . . . . . . . . . . . . . .249
19. Cardiac Cellular Electrophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .295
Hon-Chi Lee, MD, PhD
20. Normal and Abnormal Cardiac Electrophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .309
21. Indications for Electrophysiologic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .321
Michael J. Osborn, MD
22. Cardiac Channelopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .335
T. Jared Bunch, MD, Michael J. Ackerman, MD, PhD
23. Pediatric Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .345
Co-burn J. Porter, MD
24. Atrial Fibrillation: Pathogenesis, Diagnosis, and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .351
Paul A. Friedman, MD
25. Atrial Fibrillation: Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .363
David J. Bradley, MD, PhD
26. Atrial Flutter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .371
Yong-Mei Cha, MD
27. Supraventricular Tachycardia: Diagnosis and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .379
Samuel J. Asirvatham, MD
28. Ventricular Tachycardia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .389
Thomas M. Munger, MD
29. Arrhythmias in Congenital Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .405
Peter A. Brady, MD
30. Arrhythmias During Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .415
Peter A. Brady, MD
31. Heritable Cardiomyopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .425
Shaji C. Menon, MD, Steve R. Ommen, MD, Michael J. Ackerman, MD, PhD
32. Syncope: Diagnosis and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .443
Win-Kuang Shen, MD
33. Pacemakers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .455
David L. Hayes, MD, Margaret A. Lloyd, MD
34. Cardiac Resynchronization Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .467
David L. Hayes, MD
35. Technical Aspects of Implantable Cardioverter-Defibrillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .473
Robert F. Rea, MD
36. Implantable Cardioverter-Defibrillator Trials and Prevention
of Sudden Cardiac Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .481
Margaret A. Lloyd, MD, Bernard J. Gersh, MB, ChB, DPhil
37. Sudden Cardiac Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .493
Ravi Kanagala, MD
xviii

38. Heart Disease in Athletes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .507
39. Atlas of Electrophysiology Tracings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .509
VALVULAR HEART DISEASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .521
40. Valvular Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .523
41. Valvular Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .535
42. Rheumatic Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .549
Andrew G. Moore, MD
43. Carcinoid and Drug-Related Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .555
Heidi M. Connolly, MD, Patricia A. Pellikka, MD
44. Prosthetic Heart Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .563
Martha A. Grogan, MD, Fletcher A. Miller, Jr, MD
45. Surgery for Cardiac Valve Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .575
Thomas A. Orszulak, MD
AORTA AND PERIPHERAL VASCULAR DISEASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .583
46. Peripheral Vascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .585
47. Cerebrovascular Disease and Carotid Stenting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .595
Peter C. Spittell, MD, David R. Holmes, Jr, MD
48. The Aorta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .601
49. Renovascular Disease and Renal Artery Stenting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .613
Verghese Mathew, MD
50. Pathophysiology of Arterial Thrombosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .625
Robert D. McBane, MD, Waldemar E. Wysokinski, MD
51. Treatment and Prevention of Arterial Thrombosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .635
Robert D. McBane, MD, Waldemar E. Wysokinski, MD
52. Venous and Lymphatic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .655
Raymond C. Shields, MD
53. Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .663
Paul W. Wennberg, MD
54. Marfan Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .673
Naser M. Ammash, MD, Heidi M. Connolly, MD
xix

CORONARY ARTERY DISEASE RISK FACTORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .685
55. Coronary Heart Disease Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .687
56. Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .695
57. Pathogenesis of Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .699
Joseph L. Blackshear, MD, Birgit Kantor, MD, PhD
58. Dyslipidemia and Classical Factors for Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .715
Francisco Lopez-Jimenez, MD, MS, Justo Sierra Johnson, MD, MS, Virend K. Somers, MD, PhD,
Gerald T. Gau, MD
59. Novel Risk Markers for Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .725
Iftikhar J. Kullo, MD
60. Diabetes Mellitus and Coronary Artery Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .735
Robert L. Frye, MD, David R. Holmes, Jr, MD
61. Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .741
Michael J. Hogan, MD, MBA
62. Heart Disease in Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .751
Patricia J. M. Best, MD, Sharonne N. Hayes, MD
63. Heart Disease in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .761
Imran S. Syed, MD, Joseph G. Murphy, MD, R. Scott Wright, MD
64. Erectile Dysfunction and Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .767
Bijoy K. Khandheria, MD, Ajay Nehra, MD
MYOCARDIAL INFARCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .771
65. Cardiac Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .773
Brian P. Shapiro, MD, Luciano Babuin, MD, Allan S. Jaffe, MD
66. Acute Coronary Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .781
Anthony A. Hilliard, MD, Stephen L. Kopecky, MD
67. Chronic Stable Angina . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .795
Frank C. Chen, MD, Frank V. Brozovich, MD, PhD
68. Right Ventricular Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .807
Richard J. Gumina, MD, R. Scott Wright, MD, Joseph G. Murphy, MD
69. Adjunctive Therapy in Acute Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .813
R. Scott Wright, MD, Imran S. Syed, MD, Joseph G. Murphy, MD
70. Complications of Acute Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .827
Joseph G. Murphy, MD, John F. Bresnahan, MD, Margaret A. Lloyd, MD,
Guy S. Reeder, MD
71. Reperfusion Strategy for ST-Elevation Myocardial Infarction:
Fibrinolysis Versus Percutaneous Coronary Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .843
Henry H. Ting, MD
72. Fibrinolytic Trials in Acute Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .855
Patricia J. M. Best, MD, Bernard J. Gersh, MB, ChB, DPhil, Joseph G. Murphy, MD
xx

73. Risk Stratification After Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .869
Randal J. Thomas, MD, MS
74. Cardiac Rehabilitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .875
75. Coronary Artery Bypass Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .883
Thoralf M. Sundt III, MD
DISEASES OF THE HEART, PERICARDIUM, AND PULMONARY CIRCULATION . . . . . . . . . . . . . . . .891
76. Pericardial Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .893
Jae K. Oh, MD
77. Pulmonary Embolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .913
Jason M. Golbin, DO, Udaya B. S. Prakash, MD
78. Pulmonary Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .929
Michael D. McGoon, MD
79. Pregnancy and the Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .951
Heidi M. Connolly, MD
80. Adult Congenital Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .965
Carole A. Warnes, MD
81. HIV Infection and the Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .977
Joseph G. Murphy, MD, Zelalem Temesgen, MD
82. Infective Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .983
Robin Patel, MD, Joseph G. Murphy, MD, James M. Steckelberg, MD
83. Systemic Disease and the Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1017
Marian T. McEvoy, MD, Joseph G. Murphy, MD
84. Cardiac Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1027
85. Sleep Apnea and Cardiac Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1035
Tomas Kara, MD, PhD, Robert Wolk, MD, PhD, Virend K. Somers, MD, PhD
86. Cardiovascular Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1043
87. Acute Brain Injury and the Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1049
Nandan S. Anavekar, MB, BCh, Sarinya Puwanant, MD, Krishnaswamy Chandrasekaran, MD
88. Noncardiac Anesthesia in Patients With Cardiovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . .1057
Laurence C. Torsher, MD
CARDIOMYOPATHY AND HEART FAILURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1069
89. Cardiovascular Reflexes and Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1071
Alfredo L. Clavell, MD, John C. Burnett, Jr, MD
90. Systolic Heart Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1077
Wayne L. Miller, MD, PhD, Lyle J. Olson, MD
91. Diastolic Heart Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1087
Christopher P. Appleton, MD
xxi

92. Heart Failure: Diagnosis and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1101
Richard J. Rodeheffer, MD, Margaret M. Redfield, MD
93. Pharmacologic Therapy of Systolic Ventricular Dysfunction and Heart Failure . . . . . . . . . . . . . . .1113
Richard J. Rodeheffer, MD, Margaret M. Redfield, MD
94. Myocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1125
Leslie T. Cooper, Jr, MD, Oyere K. Onuma, BS
95. Dilated Cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1139
Horng H. Chen, MD
96. Restrictive Cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1145
Sudhir S. Kushwaha, MD
97. Hypertrophic Cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1153
Steve Ommen, MD
98. Right Ventricular Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1167
Robert P. Frantz, MD
99. Congestive Heart Failure: Surgical Therapy and Permanent Mechanical Support . . . . . . . . . . . . .1173
Richard C. Daly, MD, Brooks S. Edwards, MD
100. Cardiac Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1179
Brooks S. Edwards, MD, Richard C. Daly, MD
CARDIAC PHARMACOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1187
101. Principles of Pharmacokinetics and Pharmacodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1189
Arshad Jahangir, MD, Leonid V. Zingman, MD, Andre Terzic, MD, PhD
102. Antiarrhythmic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1205
Peter A. Brady, MD
103. Modulators of the Renin-Angiotensin System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1223
Garvan C. Kane, MD, Peter A. Brady, MD
104. Principles of Diuretic Usage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1231
Garvan C. Kane, MD, Joseph G. Murphy, MD
105. Digoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1233
Arshad Jahangir, MD
106. Principles of Inotropic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1245
Garvan C. Kane, MD, Joseph G. Murphy, MD, Arshad Jahangir, MD
107. Nitrate Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1249
Garvan C. Kane, MD, Peter A. Brady, MD
108. Calcium Channel Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1253
Arshad Jahangir, MD
109. ββ-Adrenoceptor Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1265
Arshad Jahangir, MD
110. Antiplatelet Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1283
Garvan C. Kane, MD, Yong-Mei Cha, MD, Joseph G. Murphy, MD
111. Cardiac Drug Adverse Effects and Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1291
Narith N. Ou, PharmD, Lance J. Oyen, PharmD, Arshad Jahangir, MD
xxii

112. Lipid-Lowering Medications and Lipid-Lowering Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . .1309
INVASIVE AND INTERVENTIONAL CARDIOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1325
113. Endothelial Dysfunction and Cardiovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1327
Brian P. Shapiro, MD, Amir Lerman, MD
114. Coronary Artery Physiology and Intracoronary Ultrasonography . . . . . . . . . . . . . . . . . . . . . . . . . .1343
Abhiram Prasad, MD
115. Coronary Anatomy and Angiographic Views . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1357
André C. Lapeyre III, MD
116. Principles of Interventional Cardiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1369
Gregory W. Barsness, MD, Joseph G. Murphy, MD
117. High-Risk Percutaneous Coronary Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1381
118. Invasive Hemodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1393
119. Contrast-Induced Nephropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1407
Patricia J. M. Best, MD, Charanjit S. Rihal, MD
120. Diagnostic Coronary Angiography and Ventriculography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1413
121. Catheter Closure of Intracardiac Shunts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1441
Guy S. Reeder, MD
122. Atlas of Hemodynamic Tracings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1451
Deepak R. Talreja, MD, Rick A. Nishimura, MD, Joseph G. Murphy, MD
123. Endomyocardial Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1481
Joseph G. Murphy, MD, Robert P. Frantz, MD, Leslie T. Cooper, Jr, MD
124. Coronary Stents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1489
Joseph G. Murphy, MD, Gregory W. Barsness, MD
125. Cardiac Emergencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1503
Arshad Jahangir, MD, Joseph G. Murphy, MD
126. Cardiogenic Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1515
Malcolm R. Bell, MD
APPENDIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1525
Preparing for Cardiology Examinations
Joseph G. Murphy, MD, Margaret A. Lloyd, MD
CREDIT LINES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1541
INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1553
xxiii

S E C T I O N I
Fundamentals of
Cardiovascular Disease
Transected Aorta: Motor Vehicle Accident

GENERAL APPEARANCE
The physical examination, including the general
appearance of the patient, is an extremely important
component of cardiology examinations. Almost every
question has physical examination findings that
provide critical clues to the answer in the stem of the
question. Important clues to a cardiac diagnosis can be
obtained from inspection of the patient (Table 1).
BLOOD PRESSURE
Blood pressure should always be determined in both
arms and in the legs if there is any suspicion of coarcta-
tion of the aorta.A difference in systolic blood pressure
between both arms of more than 10 mm Hg is abnor-
mal (Table 2).
ABNORMALITIES ON PALPATION OF THE
PRECORDIUM
The patient should be examined in both the supine
and the left lateral decubitus position. Examining the
apical impulse by the posterior approach with the
patient in the sitting position may at times be the best
method to appreciate subtle abnormalities of precordial
motion.The normal apical impulse occurs during early
systole with an outward motion imparted to the chest
wall. During mid and late systole, the left ventricle
(LV) is diminishing in volume and the apical impulse
moves away from the chest wall.Thus,outward precor-
dial apical motion occurring in late systole is abnormal.
Remember that point of maximal impulse is not synony-
mous with apical impulse.
Palpation of the Apex
Constrictive pericarditis or tricuspid regurgitation pro-
duces a subtle systolic precordial retraction.
The apical impulse of LV enlargement is usually
widened or diffuse (>3 cm in diameter), can be palpat-
ed in two interspaces, and is displaced leftward. A sub-
tle presystolic ventricular rapid filling wave (A wave)—
frequently associated with LV hypertrophy—may be
better visualized than palpated by observing the
motion of the stethoscope applied lightly on the chest
wall,with appropriate timing during simultaneous aus-
cultation. Likewise, a palpable A wave can be detected
in this manner.The apical impulse of LV hypertrophy
without dilatation is sustained and localized but should
not be displaced.
Causes of a palpable A wave (presystolic impulse)
include the following:
1. Aortic stenosis
2. Hypertrophic obstructive cardiomyopathy
3. Systemic hypertension
3
CARDIOVASCULAR EXAMINATION
Clarence Shub, MD
1

4 Section I Fundamentals of Cardiovascular Disease
Table 1. Clinical Clues to Specific Cardiac Abnormalities Detectable From the General Examination
Condition Appearance Associated cardiac abnormalities
Marfan syndrome Tall Aortic root dilatation
Long extremities Mitral valve prolapse
Acromegaly Large stature Cardiac hypertrophy
Coarse facial features
“Spade” hands
Turner syndrome Web neck Aortic coarctation
Hypertelorism Pulmonary stenosis
Short stature
Pickwickian syndrome Severe obesity Pulmonary hypertension
Somnolence
Friedreich ataxia Lurching gait Hypertrophic cardiomyopathy
Hammertoe
Pes cavus
Duchenne type muscular dystrophy Pseudohypertrophy of calves Cardiomyopathy
Ankylosing spondylitis Straight back syndrome Aortic regurgitation
Stiff (“poker”) spine Heart block (rare)
Jaundice Yellow skin or sclera Right-sided congestive heart failure
Prosthetic valve dysfunction
(hemolysis)
Sickle cell anemia Cutaneous ulcers Pulmonary hypertension
Painful “crises” Secondary cardiomyopathy
Lentigines (LEOPARD syndrome*) Brown skin macules that do Hypertrophic obstructive cardio-
not increase with sunlight myopathy
Pulmonary stenosis
Hereditary hemorrhagic telangiectasia Small capillary hemangiomas Pulmonary arteriovenous fistula
(Osler-Weber-Rendu disease) on face or mouth, with or
without cyanosis
Pheochromocytoma Pale, diaphoretic skin Catecholamine-induced secondary
Neurofibromatosis—café-au- dilated cardiomyopathy
lait spots
Lupus Butterfly rash on face Verrucous endocarditis
Raynaud phenomenon—hands Myocarditis
Livedo reticularis Pericarditis
Sarcoidosis Cutaneous nodules Secondary cardiomyopathy
Erythema nodosum Heart block
Tuberous sclerosis Angiofibromas (face; adenoma Rhabdomyoma
sebaceum)
Myxedema Coarse, dry skin Pericardial effusion
Thinning of lateral eyebrows Left ventricular dysfunction
Hoarseness of voice
Right-to-left intracardiac shunt Cyanosis and clubbing of distal Any of the lesions that cause
extremities Eisenmenger syndrome
Differential cyanosis and Reversed shunt through patent duc-
clubbing tus arteriosus

■ The apical impulse of LV hypertrophy without
dilatation is sustained and localized. It should not be
displaced but may be accompanied by a palpable
presystolic outward movement,the A wave.
■ Outward precordial apical motion occurring in late
systole is abnormal.
■ Multiple abnormal outward precordial movements
may occur: presystolic, systolic, or late systolic
rebound and an A wave in late diastole.
Palpation of the Lower Sternal Area
Precordial motion in the lower sternal area usually
reflects right ventricular (RV) motion.RV hypertrophy
due to systolic overload (such as in pulmonary stenosis)
causes a sustained outward lift. Diastolic overload
(such as in atrial septal defect [ASD]) causes a vigorous
nonsustained motion. In severe mitral regurgitation,
the left atrium expands in systole but is limited in its
posterior motion by the spine.The RV may then be
pushed forward, and the parasternal region is “lifted”
indirectly.
Significant overlap of sites of maximal pulsation
occurs in LV and RV overload states. For example, in
RV overload, the abnormal impulse can overlap with
the LV in the apical sternal region (between the apex
and the left lower sternal border). An LV apical
aneurysm may produce a delayed outward motion and
cause a “rocking”motion.
Palpation of the Left Upper Sternal Area
Abnormal pulsations at the left upper sternal border
(pulmonic area) can be due to a dilated pulmonary
artery (e.g., poststenotic dilatation in pulmonary valve
stenosis, idiopathic dilatation of the pulmonary artery,
or increased pulmonary flow related to ASD or pul-
Chapter 1 Cardiovascular Examination 5
Table 1. (continued)
Condition Appearance Associated cardiac abnormalities
Holt-Oram syndrome Rudimentary or absent thumb Atrial septal defect
Down syndrome Mental retardation Endocardial cushion defect
Simian crease of palm
Characteristic facies
Scleroderma Tight, shiny skin of fingers Pulmonary hypertension
with contraction Myocardial, pericardial, or endocar-
Characteristic taut mouth dial disease
and facies
Rheumatoid arthritis Typical hand deformity Myocardial, pericardial, or endo-
Subcutaneous nodules cardial disease (often subclinical)
Thoracic bony abnormality Pectus excavatum Pseudocardiomegaly
Straight back syndrome Mitral valve prolapse
Carcinoid syndrome Reddish cyanosis of face Right-sided cardiac valve stenosis or
Periodic flushing regurgitation
*LEOPARD syndrome: lentigines, electrocardiographic changes, ocular hypertelorism, pulmonary stenosis, abnormal genitalia,
retardation of growth, deafness.
Table 2. Causes of Blood Pressure Discrepancy
Between Arms or Between Arms and
Legs
Arterial occlusion or stenosis of any cause
Dissecting aortic aneurysm
Coarctation of the aorta
Patent ductus arteriosus
Supravalvular aortic stenosis
Thoracic outlet syndrome

monary hypertension). Pulsations of increased blood
flow are dynamic and quick, whereas pulsations due to
pressure overload cause a sustained impulse.
■ If the apical impulse is not palpable and the patient
is hemodynamically unstable, consider cardiac tam-
ponade as the first diagnosis.
Palpation of the Right Upper Sternal Area
Abnormal pulsations at the right upper sternal border
(aortic area) should suggest an aortic aneurysm. An
enlarged left lobe of the liver associated with severe tri-
cuspid regurgitation may be appreciated in the epigas-
trium,and the epigastric site may be the location of the
maximal cardiac impulse in patients with emphysema
or an enlarged RV.
■ RV hypertrophy due to systolic overload causes a
sustained outward lift. Diastolic overload (as in
ASD) causes a vigorous nonsustained motion.
■ In severe mitral regurgitation,the left atrium expands
in systole but is limited in its posterior motion by the
spine.The RV may then be pushed forward, and the
parasternal region is “lifted”indirectly.
■ Significant overlap of sites of maximal pulsation
occurs in LV and RV overload states.
■ Pulsations of increased blood flow are dynamic and
quick, whereas pulsations due to pressure overload
cause a sustained impulse.
JUGULAR VEINS
Abnormal waveforms in the jugular veins reflect
abnormal hemodynamics of the right side of the heart.
In the presence of normal sinus rhythm, there are two
positive or outward moving waves (a and v) and two
visible negative or inward moving waves (x and y) (Fig.
1).The x descent is sometimes referred to as the systolic
collapse. Ordinarily, the c wave is not readily visible.The
a wave can be identified by simultaneous auscultation
of the heart and inspection of the jugular veins.The a
wave occurs at about the time of the first heart sound
(S1).The x descent follows.The v wave,a slower,more
undulating wave, occurs near the second heart sound
(S2).The y descent follows.The a wave is normally
larger than the v wave, and the x descent is more
marked than the y descent (Tables 3 and 4).
Normal jugular venous pressure decreases with
inspiration and increases with expiration.Veins that fill
at inspiration (Kussmaul sign), however, are a clue to
constrictive pericarditis, pulmonary embolism, or RV
infarction (Table 5).
■ Jugular veins that fill at inspiration (Kussmaul sign)
are a clue to constrictive pericarditis, pulmonary
embolism,or RV infarction.
“Hepatojugular” (Abdominojugular) Reflux Sign
The neck veins distend with steady (>10 seconds)
upper abdominal compression while the patient con-
tinues to breathe normally without straining. Straining
may cause a false-positive “hepatojugular”reflux sign.
The neck veins may collapse or remain distended.
Jugular venous pressure that remains increased and
then falls abruptly (≥4 cm H2O) indicates an abnormal
response. It may occur in LV failure with secondary
pulmonary hypertension.In patients with chronic con-
gestive heart failure,a positive hepatojugular reflux sign
(with or without increased jugular venous pressure), a
third heart sound (S3), and radiographic pulmonary
vascular redistribution are independent predictors of
increased pulmonary capillary wedge pressure.The
Fig. 1. Normal jugular venous pulse. The jugular v wave
is built up during systole, and its height reflects the rate
of filling and the elasticity of the right atrium. Between
the bottom of the y descent (y trough) and the begin-
ning of the a wave is the period of relatively slow filling
of the “atrioventricle” or diastasis period. The wave built
up during diastasis is the h wave. The h wave height also
reflects the stiffness of the right atrium. S1, first heart
sound; S2, second heart sound.

abdominojugular maneuver can also be useful for elicit-
ing venous pulsations if they are difficult to visualize.
■ A positive “hepatojugular”(abdominojugular) reflux
sign may be found in LV failure with secondary pul-
monary hypertension.
■ If the jugular veins are engorged but not pulsatile,
consider superior vena caval obstruction.
ARTERIAL PULSE
Abnormalities of the Carotid Pulse
Hyperdynamic Carotid Pulse
A vigorous, hyperdynamic carotid pulse is consistent
with aortic regurgitation. It may also occur in other
states of high cardiac output or be caused by the wide
pulse pressure associated with atherosclerosis,especially
in the elderly.
Dicrotic and Bisferiens Pulses
A dicrotic carotid pulse occurs in myocardial failure,
especially in association with hypotension, decreased
cardiac output, and increased peripheral resistance.
Dicrotic and bisferious are the Greek and Latin terms,
respectively, for twice beating, but in cardiology they are
not equivalent. The second impulse occurs in early
diastole with the dicrotic pulse and in late systole with
the bisferiens pulse.The bisferiens pulse usually occurs
in combined aortic regurgitation and aortic stenosis,
but occasionally it occurs in pure aortic regurgitation.
Aortic Stenosis
Pulsus parvus (soft or weak) classically occurs in aortic
stenosis but can also result from severe stenosis of any
cardiac valve or can occur with low cardiac output of
Table 3. Timing of Jugular Venous Pulse Waves
a wave—precedes the carotid arterial pulse and is
simultaneous with S4, just before S1
x descent—between S1 and S2
v wave—just after S2
y descent—after the v wave in early diastole
Table 4. Abnormal Jugular Venous Pulse Waves
Increased a wave
1. Tricuspid stenosis
2. Decreased right ventricular compliance due
to right ventricular hypertrophy in severe
pulmonary hypertension
Pulmonary stenosis
Pulmonary vascular disease
3. Severe left ventricular hypertrophy due to
pressure by the hypertrophied septum on
right ventricular filling (Bernheim effect)
Hypertrophic obstructive cardiomyopathy
Rapid x descent
Cardiac tamponade
Increased v wave
Tricuspid regurgitation
Atrial septal defect
Rapid y descent (Friedreich sign)
Constrictive pericarditis
Table 5. Differentiation of Internal Jugular Vein
Pulse and Carotid Pulse
Jugular vein pulse Carotid pulse
Double peak when in Single peak
sinus rhythm
Obliterated by gentle Unaffected by
pressure gentle pressure
Changes with position Unaffected by
and inspiration position or
inspiration
any cause. Severe aortic stenosis also produces a slowly
increasing delayed pulse (pulsus tardus). Because of the
effects of aging on the carotid arteries, the typical find-
ings of pulsus parvus and pulsus tardus may be less
apparent or absent in the elderly, even with severe
degrees of aortic stenosis.
Hypertrophic Obstructive Cardiomyopathy
In hypertrophic obstructive cardiomyopathy, the ven-
tricular obstruction begins in mid systole, increases as

contraction proceeds, and decreases in late systole.The
initial carotid impulse is brisk.The pulse may be bifid
as well (Table 6).
Inequality of the carotid pulses can be due to
carotid atherosclerosis,especially in elderly patients.In a
young patient, consider supravalvular aortic stenosis.
(The right side then should have the stronger pulse.)
Aortic dissection and thoracic outlet syndrome may also
produce inequality of arterial pulses. A pulsating cervi-
cal mass,usually on the right,may be caused by athero-
sclerotic “buckling”of the right common carotid artery
and give the false impression of a carotid aneurysm.
Transmitted Murmurs
Transmitted murmurs of aortic origin,most often due to
aortic stenosis (less often due to coarctation, patent
ductus arteriosus, pulmonary stenosis, and ventricular
septal defect), decrease in intensity as the stethoscope
ascends the neck,whereas a carotid bruit is usually loud-
er higher in the neck and decreases in intensity as the
stethoscope is inched proximally toward the chest.Both
conditions may coexist,especially in elderly patients.An
abrupt change in the acoustic characteristics (pitch) of
the bruit as the stethoscope is inched upward may be a
clue to the presence of combined lesions.
Pulsus Paradoxus
Paradoxical pulse is an exaggeration of the normal (≤10
mm) inspiratory decline in arterial pressure. It occurs
classically in cardiac tamponade but occasionally with
other restrictive cardiac abnormalities, severe conges-
tive heart failure, pulmonary embolism, or chronic
obstructive pulmonary disease (Table 7).
Pulsus Alternans
Pulsus alternans (alternation of stronger and weaker
beats) rarely occurs in healthy subjects and then is tran-
sient after a premature ventricular contraction.It usually
is associated with severe myocardial failure and is
frequently accompanied by an S3,both of which impart
an ominous prognosis.Pulsus alternans may be affected
by alterations in venous return and may disappear as
congestive heart failure progresses. Electrical alternans
(alternating variation in the height of the QRS complex)
is unrelated to pulsus alternans (Table 8).
■ A dicrotic carotid pulse occurs in myocardial failure,
often in association with hypotension, decreased
cardiac output,and increased peripheral resistance.
■ Pulsus parvus (soft or weak) classically occurs in
aortic stenosis but can also result from severe stenosis
of any cardiac valve or can occur with severely low
cardiac output of any cause.
■ Because of the effects of aging on the carotid
arteries, the typical findings of pulsus parvus and
Table 6. Causes of a Double-Impulse Carotid
Arterial Pulse
Dicrotic pulse (systolic + diastolic impulse)
Cardiomyopathy
Left ventricular failure
Bisferiens pulse (two systolic impulses)
Aortic regurgitation
Combined aortic valve stenosis and regurgi-
tation (dominant regurgitation)
Bifid pulse (two systolic impulses with inter-
vening pulse collapse)
Hypertrophic cardiomyopathy
Table 7. Causes of Pulsus Paradoxus
Constrictive pericarditis
Pericardial tamponade
Severe emphysema
Severe asthma
Severe heart failure
Pulmonary embolism
Morbid obesity
Table 8. Pulsus and Electrical Alternans
Pulsus alternans
Severe heart failure
Electrical alternans
Pericardial tamponade
Large pericardial effusions

pulsus tardus may be less apparent or absent in the
elderly,even with severe degrees of aortic stenosis.
■ Inequality of the carotid pulses can be due to carotid
atherosclerosis, especially in elderly patients. In a
young patient, consider supravalvular aortic stenosis.
(The right side then should have the stronger pulse.)
■ Transmitted murmurs of aortic origin, most often
due to aortic stenosis (less often due to coarctation,
patent ductus arteriosus, pulmonary stenosis, or ven-
tricular septal defect), decrease in intensity as the
stethoscope ascends the neck,whereas a carotid bruit
is usually louder higher in the neck and decreases in
intensity as the stethoscope is inched proximally
toward the chest.
■ Paradoxical pulse occurs classically in cardiac tam-
ponade but occasionally with other restrictive cardiac
abnormalities, severe congestive heart failure, pul-
monary embolism, or chronic obstructive pulmonary
disease.
■ Pulsus alternans usually is associated with severe
myocardial failure and is frequently accompanied by
an S3,both of which impart an ominous prognosis.
Abnormalities of the Femoral Pulse
In hypertension, simultaneous palpation of radial and
femoral pulses may reveal a delay or relative weakening
of the femoral pulses, suggesting aortic coarctation.
The finding of a femoral (or carotid) bruit in an adult
suggests diffuse atherosclerosis. Fibromuscular dyspla-
sia is less common and occurs in younger patients.
HEART SOUNDS
First Heart Sound
Only the mitral (M1) and tricuspid (T1) components
of S1 are normally audible. M1 occurs before T1 and
is the loudest component. Wide splitting of S1
occurs with right bundle branch block and Ebstein
anomaly.
Factors Influencing the Intensity of S1
PR Interval
The PR interval varies inversely with the loudness of
S1—with a long PR interval, the S1 is soft; conversely,
with a short PR interval,the S1 is loud.
Mitral Valve Disease
Mitral stenosis produces a loud S1 if the valve is
pliable. When the valve becomes calcified and immo-
bile, the intensity of S1 decreases.The S1 may also be
soft in severe aortic regurgitation (related to early clo-
sure of the mitral valve) caused by LV filling from the
aorta.
The Rate of Increase of Systolic Pressure Within the LV
A loud S1 can be produced by hypercontractile states,
such as fever,exercise,thyrotoxicosis,and pheochromo-
cytoma.Conversely,a soft S1 can occur in LV failure.
If S1 seems louder at the lower left sternal border
than at the apex (implying a loud T1), suspect ASD or
tricuspid stenosis. Atrial fibrillation produces a variable
S1 intensity. (The intensity is inversely related to the
previous RR cycle length; a longer cycle length pro-
duces a softer S1.) A variable S1 intensity during a
wide complex, regular tachycardia suggests atrioven-
tricular dissociation and ventricular tachycardia.The
marked delay of T1 in Ebstein anomaly is related to
the late billowing effect of the deformed (sail-like)
anterior leaflet of the tricuspid valve as it closes in sys-
tole.Table 9 lists causes of an abnormal S1.
■ If S1 seems to be louder at the base than at the apex,
suspect an ejection sound masquerading as S1. If the
S1 is louder at the lower left sternal border than at
the apex (implying a loud T1), suspect ASD or tri-
cuspid stenosis.
Table 9. Abnormalities of S1 and Their Causes
Loud S1
Short PR interval
Mitral stenosis
Left atrial myxoma
Hypercontractile states
Soft S1
Long PR interval
Depressed left ventricular function
Early closure of mitral valve in acute severe
aortic incompetence
Ruptured mitral valve leaflet or chordae
Left bundle branch block

■ A variable S1 intensity during a wide complex, regu-
lar tachycardia suggests atrioventricular dissociation
and ventricular tachycardia.
■ The marked delay of T1 in Ebstein anomaly is relat-
ed to the late billowing effect of the deformed (sail-
like) anterior leaflet of the tricuspid valve as it closes
in systole.
Systolic Ejection Clicks (or Sounds)
The ejection click (sound) follows S1 closely and can
be confused with a widely split S1 or, occasionally, with
an early nonejection click. Clicks can originate from
the left or right side of the heart.
The three possible mechanisms for production of
the clicks are as follows:
1. Intrinsic abnormality of the aortic or pulmonary
valve,such as congenital bicuspid aortic valve
2. Pulsatile distention of a dilated great artery, as
occurs in increased flow states such as truncus
arteriosus (aortic click) or ASD (pulmonary click)
or in idiopathic dilatation of the pulmonary artery
3. Increased pressure in the great vessel, such as in
aortic or pulmonary hypertension
Because an aortic click is not usually heard with
uncomplicated coarctation, its presence should suggest
associated bicuspid aortic valve. In the latter condition,
the click diminishes in intensity, becomes “buried”in
the systolic murmur, and ultimately disappears as the
valve becomes heavily calcified and immobile later in
the course of the disease.Although a click implies cusp
mobility, its presence does not necessarily exclude
severe stenosis. A click would be expected to be absent
in subvalvular stenosis.The timing of the pulmonary
click in relationship to S1 (reflecting the isovolumic
contraction period of the RV) is associated with hemo-
dynamic severity in valvular pulmonary stenosis.With
higher systolic gradient and lower pulmonary artery
systolic pressure, the isovolumic contraction period
shortens and thus the earlier the click occurs in
relationship to S1. A pulmonary click can occur in
idiopathic dilatation of the pulmonary artery, and this
condition may be a masquerader of ASD, especially in
young adults.The pulmonary click due to valvular pul-
monary stenosis is the only right-sided heart sound
that decreases with inspiration. Most other right-sided
auscultatory events either increase in intensity with
inspiration (most commonly) or show minimal
change.The pulmonary click is best heard along the
upper left sternal border, but if it is loud enough or if
the RV is markedly dilated,it may be heard throughout
the precordium.The aortic click radiates to the aortic
area and the apex and does not change with respira-
tion.The causes of ejection clicks are listed in Table 10.
■ The presence, absence, or loudness of the ejection
click does not correlate with the degree of valvular
stenosis.
■ An aortic click is not heard with uncomplicated
coarctation; its presence should suggest associated
bicuspid aortic valve.
■ A click is absent in subvalvular or supravalvular aortic
stenosis or hypertrophic obstructive cardiomyopathy.
■ A pulmonary click can occur in idiopathic dilatation
of the pulmonary artery, a condition that may mimic
ASD,especially in young adults.
■ The pulmonary click is best heard along the upper
left sternal border.The aortic click radiates to the
aortic area and the apex and does not change with
respiration.
Mid-to-Late Nonejection Clicks (Systolic Clicks)
Nonejection clicks are most commonly due to mitral
valve prolapse. Rarely, nonejection clicks can be caused
by papillary muscle dysfunction, rheumatic mitral valve
disease, or hypertrophic obstructive cardiomyopathy.
Table 10. Causes of Ejection Clicks
Aortic click
Congenital valvular aortic stenosis
Congenital bicuspid aortic valve
Truncus arteriosus
Aortic incompetence
Aortic root dilatation or aneurysm
Pulmonary click
Pulmonary valve stenosis
Atrial septal defect
Chronic pulmonary hypertension
Tetralogy of Fallot with pulmonary valve
stenosis (absent if there is only infundibular
stenosis)
Idiopathic dilated pulmonary artery

Other rare causes of nonejection clicks (that can mas-
querade as mitral prolapse) include ventricular or atrial
septal aneurysms, ventricular free wall aneurysms, and
ventricular and atrial mobile tumors, such as myxoma.
A nonejection click not due to mitral valve prolapse
does not have the typical responses to bedside maneu-
vers found with mitral valve prolapse,as outlined below.
Mitral Valve Prolapse
Maneuvers that decrease LV volume,such as standing or
the Valsalva maneuver,move the click earlier in the car-
diac cycle.Conversely,maneuvers that increase LV vol-
ume,such as assuming the supine position and elevating
the legs,move the click later in the cardiac cycle.With a
decrease in LV volume, a systolic murmur, if present,
would become longer. Interventions that increase sys-
temic blood pressure make the murmur louder.
■ Miscellaneous causes of nonejection clicks (that can
masquerade as mitral prolapse) include ventricular or
atrial septal aneurysms, ventricular free wall
aneurysms, and ventricular and atrial mobile tumors,
such as myxoma.
■ Maneuvers that decrease LV volume, such as stand-
ing or the Valsalva maneuver, move the click earlier
in the cardiac cycle. Conversely, maneuvers that
increase LV volume, such as assuming the supine
position and elevating the legs, move the click later
in the cardiac cycle.
Second Heart Sound
S2 is often best heard along the upper and middle left
sternal border.Splitting of S2 (Fig.2) is best heard dur-
ing normal breathing with the subject in the sitting
position.
SPLITTING?
NORMAL NARROW FIXED WIDE FIXED REVERSED
Normal Pulm HT RBBB
PS
ASD
PDA (L to R shunt)
LBBB
AS
IHD
S2 + OS
S2 + S3
S2 + pericardial
knock
S2 + tumor
plop
A2 > P2
Normal
P2 > A2
Pulm HT (any) cause
AS
Pseudo:
VSD & L to R shunt
A2 vs P2?
Fig. 2. Branching logic tree for second heart sound (S2) splitting. A2, aortic closure sound; AS, aortic stenosis; ASD,
atrial septal defect; HT, hypertension; IHD, ischemic heart disease; LBBB, left bundle branch block; L to R, left-to-
right; OS, opening snap; P2, pulmonic closure sound; PDA, patent ductus arteriosus; PS, pulmonary stenosis; Pulm
HT, pulmonary hypertension; RBBB, right bundle branch block; S3, third heart sound; VSD, ventricular septal defect.

Determinants of S2 include the following:
1. Ventricularactivation(bundlebranchblockdelays
closureoftheventricle’srespectivesemilunarvalve)
2. Ejection time
3. Valve gradient (increased gradient with low pres-
sure in the great vessel delays closure)
4. Elastic recoil of the great artery (decreased elastic
recoil delays closure,such as in idiopathic dilata-
tion of the pulmonary artery)
Splitting of S2
Wide but physiologic splitting of S2 (Fig. 3) may be
due to the following:
1. Delayed electrical activation of the RV,such as in
right bundle branch block or premature ventric-
ularcontractionoriginatingintheLV(whichcon-
ducts with a right bundle branch block pattern)
2. Delay of RV contraction,such as in increased RV
stroke volume and RV failure
3. Pulmonary stenosis (prolonged ejection time)
In ASD, there is only minimal respiratory varia-
tion in S2 splitting.This is referred to as fixed splitting.
Fixed splitting should be verified with the patient in
the sitting or standing position because healthy sub-
jects occasionally appear to have fixed splitting in the
supine position.When the degree of splitting is unusu-
ally wide, especially when the pulmonary component
of the second heart sound (P2) is diminished, suspect
concomitant pulmonary stenosis. Indeed, this condi-
tion is the cause of the most widely split S2 that can be
recorded.
Wide, fixed splitting, although considered typical
of ASD, occurs in only 70% of patients with ASD.
However, persistent expiratory splitting is audible in
most. Normal respiratory variation of the S2 occurs in
up to 8% of patients with ASD. With Eisenmenger
physiology,the left-to-right shunting decreases and the
degree of splitting narrows. A pulmonary systolic ejec-
tion murmur (increased flow) is common in patients
with ASD, and with a significant left-to-right shunt, a
diastolic tricuspid flow murmur can be heard as well.
As with aortic stenosis,as pulmonary stenosis increases
in severity, P2 decreases in intensity, and ultimately S2
becomes single.
The wide splitting of S2 in mitral regurgitation
and ventricular septal defect is related to early aortic
valve closure (in ventricular septal defect, P2 is delayed
as well), which, in turn, is due to decreased LV ejection
time, but the loud pansystolic regurgitant murmur
often obscures the wide splitting of S2 so that the S2
appears to be single.
Partial anomalous pulmonary venous connection
may occur alone or in combination with ASD (most
often of the sinus venosus type). Wide splitting of S2
occurs in both conditions, but it usually shows normal
respiratory variation in isolated partial anomalous pul-
monary venous connection.
Fig. 3. Diagrammatic representation of normal and
abnormal patterns in the respiratory variation of the
second heart sound. The heights of the bars are propor-
tional to the sound intensity. A, aortic component; AS,
aortic stenosis; ASD, atrial septal defect; Exp., expira-
tion; Insp., inspiration; MI, mitral incompetence; P,
pulmonary component; PS, pulmonary stenosis; VSD,
ventricular septal defect.

Pulmonary hypertension may cause wide splitting
of S2, although the intensity of P2 is usually increased
and widely transmitted throughout the precordium.
■ Fixed splitting should be verified with the patient in
the sitting or standing position because healthy sub-
jects occasionally appear to have fixed splitting in the
supine position.
■ Wide, fixed splitting, although considered typical of
ASD,occurs in only 70% of patients with ASD.
■ Wide splitting of S2 occurs in both partial anom-
alous pulmonary venous connection and ASD, but it
usually shows normal respiratory variation in isolated
partial anomalous pulmonary venous connection.
■ Pulmonary hypertension may cause wide splitting of
S2, although the intensity of P2 is usually increased
and widely transmitted throughout the precordium.
Paradoxical (Reversed) Splitting of S2
Paradoxical splitting of S2 is usually caused by condi-
tions that delay aortic closure. Examples include the
following:
1. Electrical delay of LV contraction, such as left
bundle branch block (most commonly)
2. Mechanical delay of LV ejection, such as aortic
stenosis and hypertrophic obstructive cardio-
myopathy
3. Severe LV systolic failure of any cause
4. Patent ductus arteriosus,aortic regurgitation,and
systemic hypertension are other rare causes of
paradoxic splitting
Paradoxical splitting of S2 (that is, with normal
QRS duration) may be an important bedside clue to
significant LV dysfunction. In severe aortic stenosis,
the paradoxical splitting is only rarely recognized
because the late systolic ejection murmur obscures S2.
However, when paradoxical splitting of S2 is found in
association with aortic stenosis, usually in young adults
(assuming left bundle branch block is absent), severe
aortic obstruction is suggested. Similarly, paradoxical
splitting in hypertrophic obstructive cardiomyopathy
implies a significant resting LV outflow tract gradient.
Transient paradoxical splitting of S2 can occur with
myocardial ischemia, such as during an episode of
angina, either alone or in combination with an apical
systolic murmur of mitral regurgitation (papillary mus-
cle dysfunction) or prominent fourth heart sound (S4).
■ When paradoxical splitting of S2 is found in associa-
tion with aortic stenosis, usually in young adults
(assuming left bundle branch block is absent), severe
aortic obstruction is suggested. Similarly, paradoxical
splitting in hypertrophic obstructive cardiomyopathy
implies a significant resting LV outflow tract
gradient.
■ Transient paradoxical splitting of S2 can occur with
myocardial ischemia, such as during an episode of
angina,either alone or in combination with an apical
systolic murmur of mitral regurgitation (papillary
muscle dysfunction) or a prominent S4.
Intensity of S2
Loud S2
Ordinarily,the intensity of the aortic component of the
second heart sound (A2) exceeds that of the P2. In
adults, a P2 that is louder than A2, especially if P2 is
transmitted to the apex, implies either pulmonary
hypertension or marked RV dilatation, such that the
RV now occupies the apical zone.The latter may occur
in ASD (approximately 50% of patients). Hearing two
components of the S2 at the apex is abnormal in adults,
because ordinarily only A2 is heard at the apex.Thus,
when both components of S2 are heard at the apex in
adults,suspect ASD or pulmonary hypertension.
Soft S2
Decreased intensity of A2 or P2, which may cause a
single S2, reflects stiffening and decreased mobility of
the aortic or pulmonary valve (aortic stenosis or pul-
monary stenosis, respectively). A single S2 may also be
heard in older patients and the following cases:
1. With only one functioning semilunar valve,such
asinpersistenttruncusarteriosus,pulmonaryatre-
sia,or tetralogy of Fallot
2. When one component of S2 is enveloped in a
long systolic murmur,such as in ventricular sep-
tal defect
3. With abnormal relationships of great vessels,such
as in transposition of the great arteries
■ When both components of S2 are heard at the apex
in adults, implying an increased pulmonary compo-
nent of S2, suspect ASD or pulmonary hyper-
tension.

Opening Snap
A high-pitched snapping sound related to mitral or tri-
cuspid valve opening, when present, is abnormal and is
referred to as an opening snap (OS).This may arise
from either a doming stenotic mitral valve or tricuspid
valve, more commonly the former.The intensity of an
OS correlates with valve mobility.Rarely,an OS occurs
in the absence of atrioventricular valve stenosis in con-
ditions associated with increased flow through the
valve,such as significant mitral regurgitation.
In mitral stenosis, the presence of an OS, often
accompanied by a loud S1, implies a pliable mitral
valve.The OS is often well transmitted to the left ster-
nal border and even to the aortic area. In mitral steno-
sis,the absence of an OS implies the following:
1. Severe valvular immobility and calcification (note
thatanOScanstillbeheardinsomeofthesecases)
2. Mitral regurgitation is the predominant lesion
■ Significant mitral stenosis may be present in the
absence of an OS if the mitral valve leaflets are fixed
and immobile.
S2-OS Interval
The S2–mitral OS interval reflects the isovolumic
relaxation period of the LV.With increased severity of
mitral stenosis and greater increase in left atrial pres-
sures, the S2-OS interval becomes shorter and may be
confused with a split S2.The S2-OS interval should
not vary with respiration.The S2-OS interval widens
on standing, whereas the split S2 either does not
change or narrows. Mild mitral stenosis is associated
with an S2-OS interval of more than 90 ms,and severe
mitral stenosis with an interval of less than 70 ms.
However, the S2-OS interval is an unreliable predictor
of the severity of mitral stenosis. Other factors that
increase left atrial pressures, such as mitral regurgita-
tion or LV failure, can also affect this interval. When
the S2-OS interval is more than 110 to 120 ms, the
OS may be confused with an LV S3. In comparison,
the LV S3 is usually low-pitched and is localized to the
apex.
A tricuspid valve OS caused by tricuspid stenosis
can be recognized by its location along the left sternal
border and its increase with inspiration.In normal sinus
rhythm, a prominent A wave can be seen in the jugular
venous pulse,along with slowing of the Y descent.
An LV S3, which implies that rapid LV filling can
occur,is rare in pure mitral stenosis.Also,an RV S3 can
occur in mitral stenosis with severe secondary pul-
monary hypertension and RV failure. An RV S3 is
found along the left sternal border and increases with
inspiration. A tumor “plop” due to an atrial myxoma
has the same early diastolic timing as an OS and can
be confused with it.
■ In mitral stenosis, the presence of an OS, often
accompanied by a loud S1, implies a pliable mitral
valve that is not heavily calcified. (In such cases, the
patient may be a candidate for mitral commissuroto-
my or balloon valvuloplasty rather than mitral valve
replacement.)
■ In general, mild mitral stenosis is associated with an
S2-OS interval >90 ms, and severe mitral stenosis
with an interval <70 ms.
■ A tumor “plop”due to atrial myxoma has the same
early diastolic timing as an OS and can be confused
with it.
Third Heart Sound
The exact mechanism of S3 production remains con-
troversial, but its timing relates to the peak of rapid
ventricular filling with rapid flow deceleration. Factors
related to S3 intensity include the following:
1. Volumeandvelocityofbloodflowacrosstheatrio-
ventricular valve
2. Ventricular relaxation and compliance
Although a physiologic S3 can be heard in young
healthy subjects,it should not be audible after age 40.An
RV S3 may be augmented with inspiration.The physio-
logic S3 may disappear in the standing position; the
pathologic S3 persists. An S3 in a patient with mitral
regurgitation implies severe regurgitation or a failing LV
or both.The presence of a diastolic flow rumble (“rela-
tive”mitral stenosis) after the S3 suggests severe mitral
regurgitation. An S3 is less common in conditions that
cause thick,poorly compliant ventricles,for example,LV
hypertrophy that occurs with pressure overload states
(such as aortic stenosis or hypertension),until late in the
disease. An S3 may occur in hypertrophic obstructive
cardiomyopathy with normal systolic function.
The pericardial knock of constrictive pericarditis is
similar to an S3 and is associated with sudden arrest of
ventricular expansion in early diastole.The pericardial

knock is of higher frequency than S3, occurs slightly
earlier in diastole, may vary with respiration, and is
more widely transmitted.The causes of S3 are listed in
Table 11.
■ An S3 in a patient with mitral regurgitation implies
severe regurgitation or a failing LV or both.
■ An S3 is less common in conditions that cause thick,
poorly compliant ventricles, for example, LV hyper-
trophy that occurs with pressure overload states.
■ The pericardial knock is of higher frequency than
S3, occurs slightly earlier in diastole, may vary with
respiration,and is more widely transmitted.
Fourth Heart Sound
The S4 is thought to originate within the ventricular
cavity and results from a forceful atrial contraction into
a ventricle having limited distensibility, such as in
hypertrophy or fibrosis.It is not heard in healthy young
persons or in atrial fibrillation.
Common pathologic states in which an S4 is often
present include the following:
1. Aortic stenosis
2. Hypertension
3. Hypertrophic obstructive cardiomyopathy
4. Pulmonary stenosis
5. Ischemic heart disease
As the S4 becomes closer to S1,the intensity of the
latter increases. Sitting or standing may attenuate the
S4. A loud S4 can be heard in acute mitral regurgita-
tion (e.g.,with ruptured chordae tendineae) or regurgi-
tation of recent onset (the left atrium has not yet sig-
nificantly dilated). With chronic mitral regurgitation
due to rheumatic disease, the left atrium dilates,
becomes more distensible, and generates a less forceful
contraction. Under these circumstances, an S4 is usual-
ly absent. An S4 can still be heard in patients with LV
hypertrophy or ischemic heart disease, despite enlarge-
ment of the left atrium.
Although an S4 can be heard in otherwise healthy
elderly patients, a palpable S4 (a wave) should not be
present unless the LV is abnormal.An S4 can originate
from the RV. A right-sided S4 is increased in intensity
with inspiration, is often associated with large jugular
venous a waves, and is best heard along the left sternal
border rather than at the apex (this is the usual site of
an LV S4).
In patients with aortic stenosis who are younger than
40 years,the presence of an S4 usually indicates signifi-
cant obstruction.Similarly,the presence of right-sided S4,
in association with pulmonary stenosis,indicates severe
pulmonary valve obstruction.An S4 is present in most
patients with hypertrophic obstructive cardiomyopathy
and in patients with acute myocardial infarction and is
often heard in patients with systemic hypertension.
■ A loud S4 can be heard in acute mitral regurgitation
(e.g., with ruptured chordae tendineae) and can be a
clue that the regurgitation is of recent onset.
■ Although an S4 can be heard in otherwise healthy
elderly patients,a palpable S4 (a wave) should not be
present unless the LV is abnormal.
■ An S4 is present in most patients with hypertrophic
obstructive cardiomyopathy and in patients with
acute myocardial infarction and is often heard in
patients with systemic hypertension.
CARDIAC MURMURS
Systolic Murmurs
Systolic murmurs (Fig. 4) may be divided into two
categories:
Table 11. Causes of S3
Physiologic in young adults and children
Severe left ventricular dysfunction of any cause
Left ventricular dilatation without failure due to
Mitral regurgitation
Ventricular septal defect
Patent ductus arteriosus
Right ventricular S3 in right ventricular failure
and severe tricuspid regurgitation
Pericardial knock in constrictive pericarditis
S3 is augmented in intensity with an increase in
venous return due to
Leg elevation
Exercise
Release phase of Valsalva maneuver
S3 is augmented in intensity with increased sys-
temic peripheral resistance due to sustained
handgrip

Fig. 4. Sketches of various murmurs and heart sounds.
A1, Short, midsystolic murmur with normal aortic (A2)
and pulmonic (P2) components of the second heart
sound (S2)—findings consistent with an innocent
murmur.
A2, Holosystolic murmur that decreases in the latter
part of systole—a configuration observed in acute mitral
regurgitation.
A3, An ejection sound and a short early systolic
murmur, plus accentuated, closely split S2—consistent
with pulmonary hypertension, as with an Eisenmenger
ventricular septal defect.
B1, Early to midsystolic murmur with vibratory compo-
nent—typical of an innocent murmur.
B2, An ejection sound followed by a diamond-shaped
murmur and wide splitting of S2 that may be present
with atrial septal defect or mild pulmonic stenosis; an
ejection sound is more likely with valvular pulmonic
stenosis.
B3, Crescendo-decrescendo systolic murmur, not
holosystolic; the third heart sound (S3) and fourth heart
sound (S4) are present—findings consistent with mitral
systolic murmur heard in congestive cardiomyopathy or
coronary artery disease with papillary muscle dysfunc-
tion and cardiac decompensation.
C1, Longer, somewhat vibratory crescendo-decrescendo
systolic murmur with wide splitting of S2. If S2
becomes fused with expiration, atrial septal defect is less
likely; if the remainder of the cardiovascular evaluation
is normal, this finding is consistent with an innocent
murmur.
C2, Midsystsolic murmur and wide splitting of S2 that
was “fixed”—findings typical of atrial septal defect.
C3, Prolonged diamond-shaped systolic murmur mask-
ing A2 with delayed P2, S4, and ejection sound—find-
ings typical of valvular pulmonic stenosis of moderate
severity.
D1, Late apical systolic murmur of prolapsing mitral
valve leaflet.
D2, Systolic click—late apical systolic murmur of pro-
lapsing mitral leaflet syndrome.
D3, S4 and midsystolic murmur consistent with mitral
systolic murmur of cardiomyopathy or ischemic heart
disease.
E1, Early crescendo-decrescendo systolic murmur end-
ing in midsystole consistent with innocent murmur and
small ventricular septal defect.
E2 and E3, Holosystolic murmur consistent with mitral
or tricuspid regurgitation, and ventricular septal defect.
1. Ejection types, such as aortic or pulmonary
stenosis
2. Pansystolic or regurgitant types, such as mitral
regurgitation,tricuspid regurgitation,or ventric-
ular septal defect
Most, but not all, systolic murmurs fit into this
simple classification scheme. Factors that differentiate
the various causes of LV outflow tract obstruction are
shown in Table 12.The effects of various maneuvers on
murmurs and S2 are shown in Figure 5.
Aortic and Pulmonary Stenosis
Stenosis of the aortic or pulmonary valves causes a
delay in the peak intensity of the systolic murmur relat-
ed to prolongation of ejection.The magnitude of the
delay is proportional to the severity of obstruction.The
intensity (loudness) of an ejection systolic murmur may
not reflect the severity of obstruction.Thus, for exam-
ple, a patient with mild aortic stenosis or a normal
mechanical aortic prosthesis and increased cardiac
output may have a loud murmur (grade 3 or 4).
Conversely, a patient with severe aortic stenosis and
low cardiac output may have only a grade 1 or 2 mur-
mur.However,the timing of peak intensity may still be
delayed. For valvular pulmonary stenosis, early timing
of the ejection click,a widely split S2,and delayed peak
intensity of systolic murmur suggest severe stenosis.

Hypertrophic Obstructive Cardiomyopathy
Patients with hypertrophic obstructive cardiomyopathy
can have three different types and locations of systolic
murmurs:
1. Mid to lower left sternal border (LV outflow tract
obstruction)
2. Apex (associated mitral regurgitation)
3. Upper left sternal border (RV outflow tract
obstruction)—uncommon (a bedside clue is a
prominent jugular venous a wave).
Frequently, the louder systolic murmur at the mid
left sternal border, which can be widely transmitted,
may merge with or mask the others.
Aortic Stenosis Versus Aortic Sclerosis
A frequent clinical problem is the differentiation of
aortic stenosis from benign aortic sclerosis.With aortic
sclerosis, there should be no other clinical, electrocar-
diographic, or radiographic evidence of heart disease.
The systolic murmur is generally of grade 1 or 2 inten-
sity and peaks early.The carotid upstroke should be
normal. A normal S2 (that is, A2 preserved) supports a
benign process, but remember that S2 can appear sin-
gle in healthy elderly subjects.The systolic murmur of
aortic stenosis, in contrast, is delayed (peaking late in
systole) and is usually louder, and the carotid pulse is
weakened and delayed (parvus et tardus) (remember
the exception of the elderly, who may have normal
carotid pulses despite having significant aortic steno-
sis).The apical impulse in aortic stenosis is frequently
abnormal also (see the “Abnormalities on Palpation of
the Precordium”section above).
Supravalvular Aortic Stenosis
The systolic murmur of supravalvular aortic stenosis is
maximal in the first or second right intercostal space,
and a carotid pulse inequality may be present (see the
“Abnormalities of the Carotid Pulse” section above).
Patients are usually young. (The differential diagnosis
of LV outflow tract obstruction is shown in Table 12.)
Table 12. Factors That Differentiate the Various Causes of Left Ventricular Outflow Tract Obstruction
Feature Valvular Supravalvular Discrete subvalvular HOCM
Valve calcification Common after Absent Absent Absent
age 40 y
Dilated ascending aorta Common Rare Rare Rare
PP after VPB Increased Increased Increased Decreased
Valsalva effect on SM Decreased Decreased Decreased Increased
Murmur of AR Common Rare Sometimes Absent
Fourth heart sound (S4) If severe Uncommon Uncommon Common
Paradoxical splitting Sometimes* Absent Absent Common*
Ejection click Most (unless Absent Absent Uncommon or
valve calcified) absent
Maximal thrill & 2nd RIS 1st RIS 2nd RIS 4th LIS
murmur
Carotid pulse Normal to Unequal Normal to anacrotic Brisk, jerky; systolic
anacrotic* rebound
(parvus et
tardus)
AR, aortic regurgitation; HOCM, hypertrophic obstructive cardiomyopathy; LIS, left intercostal space; PP, pulse pressure; RIS,
right intercostal space; SM, systolic murmur; VPB, ventricular premature beat.

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