2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for... Management of Patients With Valvular Heart Disease: A Report of...

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2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the
Management of Patients With Valvular Heart Disease: A Report of the American College
of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing
Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular
Heart Disease): Endorsed by the Society of Cardiovascular Anesthesiologists, Society for
Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons
2006 WRITING COMMITTEE MEMBERS, Robert O. Bonow, Blase A. Carabello, Kanu
Chatterjee, Antonio C. de Leon, Jr, David P. Faxon, Michael D. Freed, William H. Gaasch,
Bruce W. Lytle, Rick A. Nishimura, Patrick T. O'Gara, Robert A. O'Rourke, Catherine M. Otto,
Pravin M. Shah and Jack S. Shanewise
Circulation. 2008;118:e523-e661; originally published online September 26, 2008;
doi: 10.1161/CIRCULATIONAHA.108.190748
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2008 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the
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Practice Guideline
Guideline
2008 Focused UpdatePractice
Incorporated
Into the ACC/AHA 2006
Guidelines for the Management of Patients With Valvular
Heart Disease
A Report of the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines (Writing Committee to Revise the 1998
Guidelines for the Management of Patients With Valvular Heart Disease)
Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular
Angiography and Interventions, and Society of Thoracic Surgeons
2006 WRITING COMMITTEE MEMBERS
Robert O. Bonow, MD, MACC, FAHA, Chair; Blase A. Carabello, MD, FACC, FAHA;
Kanu Chatterjee, MB, FACC; Antonio C. de Leon, Jr, MD, FACC, FAHA;
David P. Faxon, MD, FACC, FAHA; Michael D. Freed, MD, FACC, FAHA;
William H. Gaasch, MD, FACC, FAHA; Bruce W. Lytle, MD, FACC, FAHA;
Rick A. Nishimura, MD, FACC, FAHA; Patrick T. O’Gara, MD, FACC, FAHA;
Robert A. O’Rourke, MD, MACC, FAHA; Catherine M. Otto, MD, FACC, FAHA;
Pravin M. Shah, MD, MACC, FAHA; Jack S. Shanewise, MD*
2008 FOCUSED UPDATE WRITING GROUP MEMBERS
Rick A. Nishimura, MD, FACC, FAHA, Chair; Blase A. Carabello, MD, FACC, FAHA;
David P. Faxon, MD, FACC, FAHA; Michael D. Freed, MD, FACC, FAHA
Bruce W. Lytle, MD, FACC, FAHA; Patrick T. O’Gara, MD, FACC, FAHA;
Robert A. O’Rourke, MD, FACC, FAHA; Pravin M. Shah, MD, MACC, FAHA
TASK FORCE MEMBERS
Sidney C. Smith, Jr, MD, FACC, FAHA, Chair;
Alice K. Jacobs, MD, FACC, FAHA, Vice-Chair; Christopher E. Buller, MD, FACC;
Mark A. Creager, MD, FACC, FAHA; Steven M. Ettinger, MD, FACC;
David P. Faxon, MD, FACC, FAHA†; Jonathan L. Halperin, MD, FACC, FAHA†;
Harlan M. Krumholz, MD, FACC, FAHA; Frederick G. Kushner, MD, FACC, FAHA;
Bruce W. Lytle, MD, FACC, FAHA†; Rick A. Nishimura, MD, FACC, FAHA;
Richard L. Page, MD, FACC, FAHA; Lynn G. Tarkington, RN;
Clyde W. Yancy, Jr, MD, FACC, FAHA
*Society of Cardiovascular Anesthesiologists Representative.
†Former Task Force member during this writing effort.
This document was approved by the American College of Cardiology Foundation Board of Trustees in May 2008 and by the American Heart
Association Science Advisory and Coordinating Committee in May 2008.
The American Heart Association requests that this document be cited as follows: Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP,
Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS. 2008 Focused update incorporated
into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart
Disease). Circulation. 2008;118:e523– e661.
This article has been copublished in the Journal of the American College of Cardiology.
Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org) and the American Heart
Association (my.americanheart.org). A copy of the document is also available at http://www.americanheart.org/presenter.jhtml?identifier⫽3003999
by selecting either the “topic list” link or the “chronological list” link. To purchase additional reprints, call 843-216-2533 or e-mail
[email protected]
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express
permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/
presenter.jhtml?identifier⫽4431. A link to the “Permission Request Form” appears on the right side of the page.
(Circulation. 2008;118:e523-e661.)
© 2008 by the American College of Cardiology Foundation and the American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.108.190748
e523
Downloaded from http://circ.ahajournals.org/
by guest on September 9, 2014
e524
Circulation
October 7, 2008
TABLE OF CONTENTS
Preamble (updated) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e526
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e527
1.1. Evidence Review (UPDATED) . . . . . . . . . . . . . . . .e527
1.2. Scope of the Document (UPDATED) . . . . . . . . .e528
1.3. Review and Approval (NEW) . . . . . . . . . . . . . . . . .e529
2. General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e530
2.1. Evaluation of the Patient With a Cardiac
Murmur . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e530
2.1.1. Introduction (UPDATED) . . . . . . . . . . . . . . . . .e530
2.1.2. Classification of Murmurs . . . . . . . . . . . . . . . . .e530
2.1.2.1. Dynamic Cardiac Auscultation . . . . . . .e531
2.1.2.2. Other Physical Findings . . . . . . . . . . . . . . .e531
2.1.2.3. Associated Symptoms . . . . . . . . . . . . . . . . .e532
2.1.3. Electrocardiography and Chest
Roentgenography . . . . . . . . . . . . . . . . . . . . . . . . . . .e533
2.1.4. Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . .e533
2.1.5. Cardiac Catheterization . . . . . . . . . . . . . . . . . . . .e533
2.1.6. Exercise Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . .e533
2.1.7. Approach to the Patient . . . . . . . . . . . . . . . . . . . .e534
2.2. Valve Disease Severity Table. . . . . . . . . . . . . . . . .e535
2.3. Endocarditis and Rheumatic Fever Prophylaxis
(UPDATED). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e535
2.3.1. Endocarditis Prophylaxis (UPDATED) . . .e535
Table 5 (DELETED)
Table 6 (UPDATED)
Table 7 (UPDATED)
Table 8 (DELETED)
2.3.2. Rheumatic Fever Prophylaxis . . . . . . . . . . . . .e538
2.3.2.1. General Considerations. . . . . . . . . . . . . . . .e538
2.3.2.2. Primary Prevention . . . . . . . . . . . . . . . . . . . .e538
2.3.2.3. Secondary Prevention . . . . . . . . . . . . . . . . .e538
3. Specific Valve Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e539
3.1. Aortic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e539
3.1.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e539
3.1.1.1. Grading the Degree of Stenosis . . . . . .e539
3.1.2. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . .e540
3.1.3. Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e540
3.1.4. Management of the Asymptomatic
Patient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e541
3.1.4.1. Echocardiography (Imaging, Spectral,
and Color Doppler) in Aortic
Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e542
3.1.4.2. Exercise Testing . . . . . . . . . . . . . . . . . . . . . . .e542
3.1.4.3. Serial Evaluations . . . . . . . . . . . . . . . . . . . . .e543
3.1.4.4. Medical Therapy (UPDATED) . . . . . . .e543
3.1.4.5. Physical Activity and Exercise . . . . . . .e543
3.1.5. Indications for Cardiac Catheterization . . .e543
3.1.6. Low-Flow/Low-Gradient Aortic Stenosis. . .e544
3.1.7. Indications for Aortic Valve Replacement. .e544
3.1.7.1. Symptomatic Patients . . . . . . . . . . . . . . . . .e545
3.1.7.2. Asymptomatic Patients . . . . . . . . . . . . . . . .e546
3.1.7.3. Patients Undergoing Coronary Artery
Bypass or Other Cardiac Surgery . . . .e546
3.1.8. Aortic Balloon Valvotomy . . . . . . . . . . . . . . . .e546
3.1.9. Medical Therapy for the Inoperable
Patient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e547
3.1.10. Evaluation After Aortic Valve
Replacement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e547
3.1.11. Special Considerations in the Elderly . . .e547
3.2. Aortic Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . .e547
3.2.1. Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e547
3.2.2. Acute Aortic Regurgitation . . . . . . . . . . . . . . . .e548
3.2.2.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . .e548
3.2.2.2. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e548
3.2.2.3. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e548
3.2.3. Chronic Aortic Regurgitation . . . . . . . . . . . . . .e548
3.2.3.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . .e548
3.2.3.2. Natural History . . . . . . . . . . . . . . . . . . . . . . . .e549
3.2.3.2.1. Asymptomatic Patients With Normal
Left Ventricular Function . . . . . . . .e549
3.2.3.2.2. Asymptomatic Patients With
Depressed Systolic Function . . . . .e550
3.2.3.2.3. Symptomatic Patients. . . . . . . . . . . . .e551
3.2.3.3. Diagnosis and Initial Evaluation. . . . . .e552
3.2.3.4. Medical Therapy . . . . . . . . . . . . . . . . . . . . . .e553
3.2.3.5. Physical Activity and Exercise . . . . . . .e554
3.2.3.6. Serial Testing . . . . . . . . . . . . . . . . . . . . . . . . . .e555
3.2.3.7. Indications for Cardiac
Catheterization . . . . . . . . . . . . . . . . . . . . . . . . .e555
3.2.3.8. Indications for Aortic Valve Replacement
or Aortic Valve Repair . . . . . . . . . . . . . . . .e556
3.2.3.8.1. Symptomatic Patients With Normal
Left Ventricular Systolic
Function . . . . . . . . . . . . . . . . . . . . . . . . . . .e556
3.2.3.8.2. Symptomatic Patients With Left
Ventricular Dysfunction . . . . . . . . . .e557
3.2.3.8.3. Asymptomatic Patients . . . . . . . . . . .e557
3.2.4. Concomitant Aortic Root Disease . . . . . . . . .e558
3.2.5. Evaluation of Patients After Aortic Valve
Replacement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e558
3.2.6. Special Considerations in the Elderly . . . . .e559
3.3. Bicuspid Aortic Valve With Dilated Ascending
Aorta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e559
3.4. Mitral Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e560
3.4.1. Pathophysiology and Natural History . . . . .e560
3.4.2. Indications for Echocardiography in Mitral
Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e561
3.4.3. Medical Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . .e563
3.4.3.1. Medical Therapy: General
(UPDATED) . . . . . . . . . . . . . . . . . . . . . . . . . .e563
3.4.3.2. Medical Therapy: Atrial Fibrillation .e563
3.4.3.3. Medical Therapy: Prevention of
Systemic Embolization . . . . . . . . . . . . . .e564
3.4.4. Recommendations Regarding Physical
Activity and Exercise . . . . . . . . . . . . . . . . . . . .e565
3.4.5. Serial Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e565
3.4.6. Evaluation of the Symptomatic
Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e565
3.4.7. Indications for Invasive Hemodynamic
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e565
3.4.8. Indications for Percutaneous Mitral
Balloon Valvotomy . . . . . . . . . . . . . . . . . . . . . . .e568
3.4.9. Indications for Surgery for Mitral
Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e570
3.4.10. Management of Patients After Valvotomy
or Commissurotomy . . . . . . . . . . . . . . . . . . . .e572
3.4.11. Special Considerations. . . . . . . . . . . . . . . . . .e572
3.4.11.1 Pregnant Patients . . . . . . . . . . . . . . . . . . . .e572
3.4.11.2. Older Patients . . . . . . . . . . . . . . . . . . . . . . .e572
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Bonow et al
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
3.5. Mitral Valve Prolapse . . . . . . . . . . . . . . . . . . . . . . . . .e573
3.5.1. Pathophysiology and Natural History . .e573
3.5.2. Evaluation and Management of the
Asymptomatic Patient (UPDATED) . . .e574
3.5.3. Evaluation and Management of the
Symptomatic Patient (UPDATED) . . . . .e574
3.5.4. Surgical Considerations . . . . . . . . . . . . . . . . . .e576
3.6. Mitral Regurgitation. . . . . . . . . . . . . . . . . . . . . . . . . . .e576
3.6.1. Etiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e576
3.6.2. Acute Severe Mitral Regurgitation . . . . .e576
3.6.2.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . .e576
3.6.2.2. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e576
3.6.2.3. Medical Therapy . . . . . . . . . . . . . . . . . . . . .e576
3.6.3. Chronic Asymptomatic Mitral
Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e577
3.6.3.1. Pathophysiology and Natural History . . .e577
3.6.3.2. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e577
3.6.3.3. Indications for Transthoracic
Echocardiography . . . . . . . . . . . . . . . . . . . . .e577
3.6.3.4. Indications for Transesophageal
Echocardiography. . . . . . . . . . . . . . . . . . . . . . . .e578
3.6.3.5. Serial Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e578
3.6.3.6. Guidelines for Physical Activity and
Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e579
3.6.3.7. Medical Therapy . . . . . . . . . . . . . . . . . . . . . .e579
3.6.3.8. Indications for Cardiac
Catheterization . . . . . . . . . . . . . . . . . . . . . . . . .e579
3.6.4. Indications for Surgery . . . . . . . . . . . . . . . . . . . .e579
3.6.4.1. Types of Surgery . . . . . . . . . . . . . . . . . . . . . .e579
3.6.4.2. Indications for Mitral Valve Operation . .e580
3.6.4.2.1. Symptomatic Patients With Normal
Left Ventricular Function . . . . . . . .e581
3.6.4.2.2. Asymptomatic or Symptomatic Patients
With Left Ventricular Dysfunction .e581
3.6.4.2.3. Asymptomatic Patients With Normal
Left Ventricular Function . . . . . . . .e581
3.6.4.2.4. Atrial Fibrillation . . . . . . . . . . . . . . . . .e582
3.6.5. Ischemic Mitral Regurgitation . . . . . . . . . . . . .e583
3.6.6. Evaluation of Patients After Mitral Valve
Replacement or Repair. . . . . . . . . . . . . . . . . . . . .e584
3.6.7. Special Considerations in the Elderly . . . . .e584
3.7. Multiple Valve Disease . . . . . . . . . . . . . . . . . . . . . . . . .e584
3.7.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e584
3.7.2. Mixed Single Valve Disease . . . . . . . . . . . . . .e584
3.7.2.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . .e584
3.7.2.2. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e584
3.7.2.2.1. Two-Dimensional and Doppler
Echocardiographic Studies . . . . . . .e584
3.7.2.2.2. Cardiac Catheterization . . . . . . . . . . .e585
3.7.2.3. Management . . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.3. Combined Mitral Stenosis and Aortic
Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.3.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.3.2. Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.4. Combined Mitral Stenosis and Tricuspid
Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.4.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.4.2. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.4.3. Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e585
3.7.5. Combined Mitral Regurgitation and Aortic
Regurgitation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e586
e525
3.7.5.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . .e586
3.7.5.2. Diagnosis and Therapy . . . . . . . . . . . . . . . .e586
3.7.6. Combined Mitral Stenosis and Aortic
Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e586
3.7.6.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . .e586
3.7.6.2. Diagnosis and Therapy . . . . . . . . . . . . . . . .e586
3.7.7. Combined Aortic Stenosis and Mitral
Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e586
3.7.7.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . .e586
3.7.7.2. Diagnosis and Therapy . . . . . . . . . . . . . . . . . . . .e586
3.8. Tricuspid Valve Disease . . . . . . . . . . . . . . . . . . . . . . . . . . .e586
3.8.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e586
3.8.2. Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e587
3.8.3. Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e587
3.9. Drug-Related Valvular Heart Disease . . . . . . . . . . . . . .e588
3.10. Radiation Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . .e588
4. Evaluation and Management of Infective Endocarditis . .e589
4.1. Antimicrobial Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e589
4.2. Culture-Negative Endocarditis. . . . . . . . . . . . . . . . . . . . . .e589
4.3. Endocarditis in HIV-Seropositive Patients . . . . . . . . . .e590
4.4. Indications for Echocardiography in
Suspected or Known Endocarditis . . . . . . . . . . . . . . . . .e591
4.4.1. Transthoracic Echocardiography in
Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e592
4.4.2. Transesophageal Echocardiography in
Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e592
4.5. Outpatient Treatment . . . . . . . . . . . . . . . . . . . . . . . . . .e593
4.6. Indications for Surgery in Patients With
Acute Infective Endocarditis . . . . . . . . . . . . . . . . .e593
4.6.1. Surgery for Native Valve
Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e595
4.6.2. Surgery for Prosthetic Valve Endocarditis . . .e596
5. Management of Valvular Disease in Pregnancy . . .e596
5.1. Physiological Changes of Pregnancy . . . . . . . . . .e596
5.2. Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . .e598
5.3. Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e598
5.4. General Management Guidelines . . . . . . . . . . . . . .e598
5.5. Specific Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e599
5.5.1. Mitral Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e599
5.5.2. Mitral Regurgitation . . . . . . . . . . . . . . . . . . . . . . .e599
5.5.3. Aortic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e599
5.5.4. Aortic Regurgitation . . . . . . . . . . . . . . . . . . . . . . .e601
5.5.5. Pulmonic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . .e601
5.5.6. Tricuspid Valve Disease . . . . . . . . . . . . . . . . . . .e601
5.5.7. Marfan Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . .e601
5.6. Endocarditis Prophylaxis (UPDATED) . . . . . . .e601
5.7. Cardiac Valve Surgery . . . . . . . . . . . . . . . . . . . . . . . . .e601
5.8. Anticoagulation During Pregnancy . . . . . . . . . . . .e602
5.8.1. Warfarin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e602
5.8.2. Unfractionated Heparin . . . . . . . . . . . . . . . . . . . .e602
5.8.3. Low-Molecular-Weight Heparins . . . . . . . . .e602
5.8.4. Selection of Anticoagulation Regimen in
Pregnant Patients With Mechanical Prosthetic
Valves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e602
5.9. Selection of Valve Prostheses in Young Women . .e604
6. Management of Congenital Valvular Heart Disease in
Adolescents and Young Adults (UPDATED) . . . . . . . . . .e604
6.1. Aortic Stenosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e604
6.1.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e604
6.1.2. Evaluation of Asymptomatic Adolescents or
Young Adults With Aortic Stenosis . . . . . . . . . . .e604
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6.1.3. Indications for Aortic Balloon Valvotomy in
Adolescents and Young Adults . . . . . . . . . . . . . . . .e605
6.2. Aortic Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e606
6.3. Mitral Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e607
6.4. Mitral Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e608
6.5. Tricuspid Valve Disease . . . . . . . . . . . . . . . . . . . . . . . . . . .e608
6.5.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e608
6.5.2. Evaluation of Tricuspid Valve Disease in
Adolescents and Young Adults . . . . . . . . . . . . . . . .e609
6.5.3. Indications for Intervention in Tricuspid
Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e609
6.6. Pulmonic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e610
6.6.1. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e610
6.6.2. Evaluation of Pulmonic Stenosis in Adolescents
and Young Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e610
6.6.3. Indications for Balloon Valvotomy in Pulmonic
Stenosis (UPDATED). . . . . . . . . . . . . . . . . . . . . . . . .e610
6.7. Pulmonary Regurgitation. . . . . . . . . . . . . . . . . . . . . . . . . . .e611
7. Surgical Considerations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e612
7.1. American Association for Thoracic Surgery/Society of
Thoracic Surgeons Guidelines for Clinical Reporting of
Heart Valve Complications . . . . . . . . . . . . . . . . . . . . . . . .e612
7.2. Aortic Valve Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e614
7.2.1. Risks and Strategies in Aortic Valve Surgery . .e614
7.2.2. Mechanical Aortic Valve Prostheses . . . . . . . . . . .e614
7.2.2.1. Antithrombotic Therapy for Patients With
Aortic Mechanical Heart Valves . . . . . . . . . .e614
7.2.3. Stented and Nonstented Heterografts. . . . . . . . . . .e614
7.2.3.1. Aortic Valve Replacement With Stented
Heterografts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e614
7.2.3.2. Aortic Valve Replacement With
Stentless Heterografts . . . . . . . . . . . . . . . . .e616
7.2.4. Aortic Valve Homografts . . . . . . . . . . . . . . . .e616
7.2.5. Pulmonic Valve Autotransplantation . . .e616
7.2.6. Aortic Valve Repair . . . . . . . . . . . . . . . . . . . . . .e617
7.2.7. Left Ventricle–to–Descending Aorta
Shunt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e617
7.2.8. Comparative Trials and Selection of Aortic
Valve Prostheses . . . . . . . . . . . . . . . . . . . . . . . . . .e617
7.2.9. Major Criteria for Aortic Valve
Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e618
7.3. Mitral Valve Surgery . . . . . . . . . . . . . . . . . . . . . . . . .e618
7.3.1. Mitral Valve Repair . . . . . . . . . . . . . . . . . . . . . .e619
7.3.1.1. Myxomatous Mitral Valve . . . . . . . . . .e619
7.3.1.2. Rheumatic Heart Disease . . . . . . . . . . .e619
7.3.1.3. Ischemic Mitral Valve Disease . . . . .e619
7.3.1.4. Mitral Valve Endocarditis . . . . . . . . . .e620
7.3.2. Mitral Valve Prostheses (Mechanical or
Bioprostheses) . . . . . . . . . . . . . . . . . . . . . . . . . . . .e620
7.3.2.1. Selection of a Mitral Valve
Prosthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e620
7.3.2.2. Choice of Mitral Valve Operation .e620
7.4. Tricuspid Valve Surgery . . . . . . . . . . . . . . . . . . . . . .e621
7.5. Valve Selection for Women of Childbearing Age .e621
8. Intraoperative Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e621
8.1. Specific Valve Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e622
8.1.1. Aortic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e622
8.1.2. Aortic Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . .e622
8.1.3. Mitral Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e622
8.1.4. Mitral Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . .e623
8.1.5. Tricuspid Regurgitation . . . . . . . . . . . . . . . . . . . . . . . .e623
8.1.6. Tricuspid Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e623
8.1.7. Pulmonic Valve Lesions . . . . . . . . . . . . . . . . . . . . . . .e623
8.2. Specific Clinical Scenarios . . . . . . . . . . . . . . . . . . . . . . . . .e623
8.2.1. Previously Undetected Aortic Stenosis During
CABG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e623
8.2.2. Previously Undetected Mitral Regurgitation During
CABG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e623
9. Management of Patients With Prosthetic Heart Valves. .e624
9.1. Antibiotic Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e624
9.1.1. Infective Endocarditis. . . . . . . . . . . . . . . . . . . . . . . . . .e624
9.1.2. Recurrence of Rheumatic Carditis . . . . . . . . . . . . .e624
9.2. Antithrombotic Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . .e624
9.2.1. Mechanical Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . .e625
9.2.2. Biological Valves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e625
9.2.3. Embolic Events During Adequate Antithrombotic
Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e626
9.2.4. Excessive Anticoagulation . . . . . . . . . . . . . . . . . . . . .e626
9.2.5. Bridging Therapy in Patients With Mechanical
Valves Who Require Interruption of Warfarin
Therapy for Noncardiac Surgery, Invasive
Procedures, or Dental Care . . . . . . . . . . . . . . . . . . . .e626
9.2.6. Antithrombotic Therapy in Patients Who Need
Cardiac Catheterization/Angiography . . . . . . . . . .e627
9.2.7. Thrombosis of Prosthetic Heart Valves . . . . . . . .e627
9.3. Follow-Up Visits. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e628
9.3.1. First Outpatient Postoperative Visit . . . . . . . . . . . .e628
9.3.2. Follow-Up Visits in Patients Without
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e629
9.3.3. Follow-Up Visits in Patients With
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e629
9.4. Reoperation to Replace a Prosthetic Valve . . . . . .e629
10. Evaluation and Treatment of Coronary Artery Disease
in Patients With Valvular Heart Disease . . . . . . . . . . . .e630
10.1. Probability of Coronary Artery Disease in Patients
With Valvular Heart Disease . . . . . . . . . . . . . . . . . . .e630
10.2. Diagnosis of Coronary Artery Disease . . . . . . . . .e630
10.3. Treatment of Coronary Artery Disease at the Time
of Aortic Valve Replacement . . . . . . . . . . . . . . . . . . .e631
10.4. Aortic Valve Replacement in Patients Undergoing
Coronary Artery Bypass Surgery . . . . . . . . . . . . . . .e631
10.5. Management of Concomitant MV Disease and
Coronary Artery Disease . . . . . . . . . . . . . . . . . . . . . . . .e632
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e633
Appendix 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e656
Appendix 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e657
Appendix 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e659
Appendix 4 (NEW). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e659
Appendix 5 (NEW). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e660
Preamble (Updated)
It is important that the medical profession play a significant
role in critically evaluating the use of diagnostic procedures
and therapies as they are introduced in the detection, management, or prevention of disease states. Rigorous and expert
analysis of the available data documenting the absolute and
relative benefits and risks of those procedures and therapies
can produce helpful guidelines that improve the effectiveness
of care, optimize patient outcomes, and favorably affect the
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overall cost of care by focusing resources on the most
effective strategies.
The American College of Cardiology (ACC) and the
American Heart Association (AHA) have jointly engaged in
the production of such guidelines in the area of cardiovascular disease since 1980. This effort is directed by the ACC/
AHA Task Force on Practice Guidelines, whose charge is to
develop, update, or revise practice guidelines for important
cardiovascular diseases and procedures. Writing committees
are charged with the task of performing an assessment of the
evidence and acting as an independent group of authors to
develop and update written recommendations for clinical
practice.
Experts in the subject under consideration are selected from
both organizations to examine subject-specific data and write
guidelines. The process includes additional representatives from
other medical practitioner and specialty groups where appropriate. Writing committees are specifically charged to perform a
formal literature review, weigh the strength of evidence for or
against a particular treatment or procedure, and include estimates
of expected health outcomes where data exist. Patient-specific
modifiers, comorbidities, and issues of patient preference that
may influence the choice of particular tests or therapies are
considered, as well as frequency of follow-up. When available,
information from studies on cost will be considered; however,
review of data on efficacy and clinical outcomes will be the
primary basis for preparing recommendations in these
guidelines.
The ACC/AHA Task Force on Practice Guidelines makes
every effort to avoid any actual, potential, or perceived
conflicts of interest that may arise as a result of an outside
relationship or personal interest of a member of the writing
committee. Specifically, all members of the writing committee and peer reviewers of the document are asked to provide
disclosure statements of all such relationships that may be
perceived as real or potential conflicts of interest. Writing
committee members are also strongly encouraged to declare a
previous relationship with industry that may be perceived as
relevant to guideline development. If a writing committee
member develops a new relationship with industry during his
or her tenure, he or she is required to notify guideline staff in
writing. The continued participation of the writing committee
member will be reviewed. These statements are reviewed by
the parent task force, reported orally to all members of the
writing panel at each meeting, and updated and reviewed by
the writing committee as changes occur. Please refer to the
methodology manual for the ACC/AHA guideline writing committees for further description and the relationships with industry
policy.1067 See Appendix 1 for a list of writing committee
member relationships with industry and Appendix 2 for a listing
of peer reviewer relationships with industry that are pertinent to
this guideline.
These practice guidelines are intended to assist healthcare
providers in clinical decision making by describing a range of
generally acceptable approaches for the diagnosis, management, and prevention of specific diseases or conditions. See
Appendix 3 for a list of abbreviated terms used in this
guideline. These guidelines attempt to define practices that
meet the needs of most patients in most circumstances. These
e527
guideline recommendations reflect a consensus of expert opinion
after a thorough review of the available, current scientific
evidence and are intended to improve patient care. If these
guidelines are used as the basis for regulatory/payer decisions,
the ultimate goal is quality of care and serving the patient’s best
interests. The ultimate judgment regarding care of a particular
patient must be made by the healthcare provider and patient in
light of all of the circumstances presented by that patient. There
are circumstances in which deviations from these guidelines are
appropriate.
The current document is a republication of the “ACC/AHA
2006 Guidelines for the Management of Patients With Valvular Heart Disease,”1068 revised to incorporate individual
recommendations from a 2008 focused update,1069 which
spotlights the 2007 AHA Guidelines for Infective Endocarditis Prophylaxis. For easy reference, this online-only version
denotes sections that have been updated. All members of the
2006 Valvular Heart Disease Writing Committee were invited to participate in the writing group; those who agreed
were required to disclose all relationships with industry
relevant to the data under consideration,1067 as were all peer
reviewers of the document. (See Appendixes 4 and 5 for a
listing of relationships with industry for the 2008 Focused
Update Writing Group and peer reviewers, respectively.)
Each recommendation required a confidential vote by the
writing group members before and after external review of
the document. Any writing group member with a significant (greater than $10 000) relationship with industry
relevant to the recommendation was recused from voting
on that recommendation.
Guidelines are reviewed annually by the ACC/AHA Task
Force on Practice Guidelines and are considered current
unless they are updated or sunsetted and withdrawn from
distribution.
Sidney C. Smith, Jr., MD, FACC, FAHA
Chair, ACC/AHA Task Force on Practice Guidelines
1. Introduction
1.1. Evidence Review (UPDATED)
The ACC and the AHA have long been involved in the joint
development of practice guidelines designed to assist healthcare providers in the management of selected cardiovascular
disorders or the selection of certain cardiovascular procedures. The determination of the disorders or procedures to
develop guidelines is based on several factors, including
importance to healthcare providers and whether there are
sufficient data from which to derive accepted guidelines. One
important category of cardiac disorders that affect a large
number of patients who require diagnostic procedures and
decisions regarding long-term management is valvular heart
disease.
During the past 2 decades, major advances have occurred
in diagnostic techniques, the understanding of natural history,
and interventional cardiology and surgical procedures for
patients with valvular heart disease. These advances have
resulted in enhanced diagnosis, more scientific selection of
patients for surgery or catheter-based intervention versus
medical management, and increased survival of patients with
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these disorders. The information base from which to make
clinical management decisions has greatly expanded in recent
years, yet in many situations, management issues remain controversial or uncertain. Unlike many other forms of cardiovascular disease, there is a scarcity of large-scale multicenter trials
addressing the diagnosis and treatment of patients with valvular
disease from which to derive definitive conclusions, and the
information available in the literature represents primarily the
experiences reported by single institutions in relatively small
numbers of patients.
The 1998 Committee on Management of Patients With
Valvular Heart Disease reviewed and compiled this information
base and made recommendations for diagnostic testing, treatment, and physical activity. For topics for which there was an
absence of multiple randomized, controlled trials, the preferred
basis for medical decision making in clinical practice (evidencebased medicine), the committee’s recommendations were based
on data derived from single randomized trials or nonrandomized
studies or were based on a consensus opinion of experts. The
2006 writing committee was charged with revising the guidelines published in 1998. The committee reviewed pertinent
publications, including abstracts, through a computerized search
of the English literature since 1998 and performed a manual
search of final articles. Special attention was devoted to identification of randomized trials published since the original document. A complete listing of all publications covering the treatment of valvular heart disease is beyond the scope of this
document; the document includes those reports that the committee believes represent the most comprehensive or convincing
data that are necessary to support its conclusions. However,
evidence tables were updated to reflect major advances over this
time period. Inaccuracies or inconsistencies present in the
original publication were identified and corrected when possible.
Recommendations provided in this document are based primarily on published data. Because randomized trials are unavailable
in many facets of valvular heart disease treatment, observational
studies, and, in some areas, expert opinions form the basis for
recommendations that are offered.
All of the recommendations in this guideline revision were
converted from the tabular format used in the 1998 guideline
to a listing of recommendations that has been written in full
sentences to express a complete thought, such that a recommendation, even if separated and presented apart from the rest
of the document, would still convey the full intent of the
recommendation. It is hoped that this will increase the
readers’ comprehension of the guidelines. Also, the level of
evidence, either A, B, or C, for each recommendation is now
provided.
Classification of recommendations and level of evidence
are expressed in the ACC/AHA format as follows:
• Class I: Conditions for which there is evidence for and/or
general agreement that the procedure or treatment is
beneficial, useful, and effective.
• Class II: Conditions for which there is conflicting evidence
and/or a divergence of opinion about the usefulness/
efficacy of a procedure or treatment.
• Class IIa: Weight of evidence/opinion is in favor of
usefulness/efficacy.
• Class IIb: Usefulness/efficacy is less well established by
evidence/opinion.
• Class III: Conditions for which there is evidence and/or
general agreement that the procedure/treatment is not
useful/effective and in some cases may be harmful.
In addition, the weight of evidence in support of the
recommendation is listed as follows:
• Level of Evidence A: Data derived from multiple randomized clinical trials.
• Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies.
• Level of Evidence C: Only consensus opinion of experts,
case studies, or standard-of-care.
The schema for classification of recommendations and
level of evidence is summarized in Fig. 1, which also
illustrates how the grading system provides an estimate of the
size of the treatment effect and an estimate of the certainty of
the treatment effect.
Writing committee membership consisted of cardiovascular disease specialists and representatives of the cardiac
surgery and cardiac anesthesiology fields; both the academic
and private practice sectors were represented. The Society of
Cardiovascular Anesthesiologists assigned an official representative to the writing committee.
1.2. Scope of the Document (UPDATED)
The guidelines attempt to deal with general issues of treatment of patients with heart valve disorders, such as evaluation
of patients with heart murmurs, prevention and treatment of
endocarditis, management of valve disease in pregnancy, and
treatment of patients with concomitant coronary artery disease (CAD), as well as more specialized issues that pertain to
specific valve lesions. The guidelines focus primarily on
valvular heart disease in the adult, with a separate section
dealing with specific recommendations for valve disorders in
adolescents and young adults. The diagnosis and management
of infants and young children with congenital valvular abnormalities are significantly different from those of the adolescent or adult and are beyond the scope of these guidelines.
This task force report overlaps with several previously
published ACC/AHA guidelines about cardiac imaging and
diagnostic testing, including the guidelines for the clinical use
of cardiac radionuclide imaging,1 the clinical application of
echocardiography,2 exercise testing,3 and percutaneous coronary intervention.4 Although these guidelines are not intended
to include detailed information covered in previous guidelines on the use of imaging and diagnostic testing, an essential
component of this report is the discussion of indications for
these tests in the evaluation and treatment of patients with
valvular heart disease.
The committee emphasizes the fact that many factors
ultimately determine the most appropriate treatment of individual patients with valvular heart disease within a given
community. These include the availability of diagnostic
equipment and expert diagnosticians, the expertise of interventional cardiologists and surgeons, and notably, the wishes
of well-informed patients. Therefore, deviation from these
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Figure 1. Applying classification of recommendations and level of evidence.
*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many
important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very
clear clinical consensus that a particular test or therapy is useful or effective. †In 2003 the ACC/AHA Task Force on Practice Guidelines recently provided a list of suggested phrases to use when writing recommendations. All recommendations in this guideline have been written in full sentences that express a complete thought, such
that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the
full intent of the recommendation. It is hoped that this will increase readers’ comprehension of the guidelines and will allow queries at the individual recommendation
level.
guidelines may be appropriate in some circumstances. These
guidelines are written with the assumption that a diagnostic
test can be performed and interpreted with skill levels
consistent with previously reported ACC training and competency statements and ACC/AHA guidelines, that interventional cardiological and surgical procedures can be performed
by highly trained practitioners within acceptable safety standards, and that the resources necessary to perform these
diagnostic procedures and provide this care are readily
available. This is not true in all geographic areas, which
further underscores the committee’s position that its recommendations are guidelines and not rigid requirements.
1.3. Review and Approval (NEW)
The 2006 document1068 was reviewed by 2 official reviewers
nominated by the ACC; 2 official reviewers nominated by the
AHA; 1 official reviewer from the ACC/AHA Task Force on
Practice Guidelines; reviewers nominated by the Society of
Cardiovascular Anesthesiologists, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic
Surgeons (STS); and individual content reviewers, including
members of the ACCF Cardiac Catheterization and Intervention
Committee, ACCF Cardiovascular Imaging Committee, ACCF
Cardiovascular Surgery Committee, AHA Endocarditis Committee, AHA Cardiac Clinical Imaging Committee, AHA Cardiovascular Intervention and Imaging Committee, and AHA
Cerebrovascular Imaging and Intervention Committee.
As mentioned previously, this document also incorporates
a 2008 focused update of the “ACC/AHA 2006 Guidelines
for the Management of Patients With Valvular Heart Disease,”1069 which spotlights the 2007 AHA Guidelines for
Infective Endocarditis Prophylaxis.1070 Only recommendations related to infective endocarditis have been revised. This
document was reviewed by 2 external reviewers nominated
by the ACC and 2 external reviewers nominated by the AHA,
as well as 3 reviewers from the ACCF Congenital Heart
Disease and Pediatric Committee, 2 reviewers from the
ACCF Cardiovascular Surgery Committee, 5 reviewers from
the AHA Heart Failure and Transplant Committee, and 3
reviewers from the Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. All information about reviewers’
relationships with industry was collected and distributed to
the writing committee and is published in this document (see
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Appendix 5 for details). This document was approved for
publication by the governing bodies of the ACCF and the
AHA in May 2008 and endorsed by the Society of Cardiovascular Anesthesiologists, the Society for Cardiovascular
Angiography and Interventions, and the Society of Thoracic
Surgeons.
2. General Principles
2.1. Evaluation of the Patient With
a Cardiac Murmur
Table 1.
Classification of Cardiac Murmurs
1. Systolic murmurs
a. Holosystolic (pansystolic) murmurs
b. Midsystolic (systolic ejection) murmurs
c. Early systolic murmurs
d. Mid to late systolic murmurs
2. Diastolic murmurs
a. Early high-pitched diastolic murmurs
b. Middiastolic murmurs
c. Presystolic murmurs
3. Continuous murmurs
2.1.1. Introduction (UPDATED)
Cardiac auscultation remains the most widely used method of
screening for valvular heart disease (VHD). The production
of murmurs is due to 3 main factors:
• high blood flow rate through normal or abnormal orifices
• forward flow through a narrowed or irregular orifice into a
dilated vessel or chamber
• backward or regurgitant flow through an incompetent
valve
Often, more than 1 of these factors is operative.5–7
A heart murmur may have no pathological significance or
may be an important clue to the presence of valvular,
congenital, or other structural abnormalities of the heart.8
Most systolic heart murmurs do not signify cardiac disease,
and many are related to physiological increases in blood flow
velocity.9 In other instances, a heart murmur may be an
important clue to the diagnosis of undetected cardiac disease
(e.g., valvular aortic stenosis [AS]) that may be important
even when asymptomatic or that may define the reason for
cardiac symptoms. In these situations, various noninvasive or
invasive cardiac tests may be necessary to establish a firm
diagnosis and form the basis for rational treatment of an
underlying disorder. Echocardiography is particularly useful
in this regard, as discussed in the “ACC/AHA/ASE 2003
Guidelines for the Clinical Application of Echocardiography.”2 Diastolic murmurs virtually always represent pathological conditions and require further cardiac evaluation, as
do most continuous murmurs. Continuous “innocent” murmurs include venous hums and mammary souffles.
The traditional auscultation method of assessing cardiac
murmurs has been based on their timing in the cardiac cycle,
configuration, location and radiation, pitch, intensity (grades
1 through 6), and duration.5–9 The configuration of a murmur
may be crescendo, decrescendo, crescendo-decrescendo
(diamond-shaped), or plateau. The precise times of onset and
cessation of a murmur associated with cardiac pathology
depend on the period of time in the cardiac cycle in which a
physiologically important pressure difference between 2
chambers occurs.5–9 A classification of cardiac murmurs is
listed in Table 1.
2.1.2. Classification of Murmurs
Holosystolic (pansystolic) murmurs are generated when there
is flow between chambers that have widely different pressures
throughout systole, such as the left ventricle and either the left
atrium or right ventricle. With an abnormal regurgitant
orifice, the pressure gradient and regurgitant jet begin early in
contraction and last until relaxation is almost complete.
Midsystolic (systolic ejection) murmurs, often crescendodecrescendo in configuration, occur when blood is ejected
across the aortic or pulmonic outflow tracts. The murmurs
start shortly after S1, when the ventricular pressure rises
sufficiently to open the semilunar valve. As ejection increases, the murmur is augmented, and as ejection declines, it
diminishes.
In the presence of normal semilunar valves, this murmur
may be caused by an increased flow rate such as that which
occurs with elevated cardiac output (e.g., pregnancy, thyrotoxicosis, anemia, and arteriovenous fistula), ejection of
blood into a dilated vessel beyond the valve, or increased
transmission of sound through a thin chest wall. Most
innocent murmurs that occur in children and young adults are
midsystolic and originate either from the aortic or pulmonic
outflow tracts. Valvular, supravalvular, or subvalvular obstruction (stenosis) of either ventricle may also cause a
midsystolic murmur, the intensity of which depends in part on
the velocity of blood flow across the narrowed area. Midsystolic murmurs also occur in certain patients with functional
mitral regurgitation (MR) or, less frequently, tricuspid regurgitation (TR). Echocardiography is often necessary to separate a prominent and exaggerated (grade 3) benign midsystolic murmur from one due to valvular AS.
Early systolic murmurs are less common; they begin with
the first sound and end in midsystole. An early systolic
murmur is often due to TR that occurs in the absence of
pulmonary hypertension, but it also occurs in patients with
acute MR. In large ventricular septal defects with pulmonary
hypertension and small muscular ventricular septal defects,
the shunting at the end of systole may be insignificant, with
the murmur limited to early and midsystole.
Late systolic murmurs are soft or moderately loud, highpitched murmurs at the left ventricular (LV) apex that start
well after ejection and end before or at S2. They are often due
to apical tethering and malcoaptation of the mitral leaflets due
to anatomic and functional changes of the annulus and
ventricle. Late systolic murmurs in patients with midsystolic
clicks result from late systolic regurgitation due to prolapse of
the mitral leaflet(s) into the left atrium. Such late systolic
murmurs can also occur in the absence of clicks.
Early diastolic murmurs begin with or shortly after S2,
when the associated ventricular pressure drops sufficiently
below that in the aorta or pulmonary artery. High-pitched
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Interventions Used to Alter the Intensity of Cardiac Murmurs
Respiration
Right-sided murmurs generally increase with inspiration. Left-sided murmurs usually are louder during expiration.
Valsalva maneuver
Most murmurs decrease in length and intensity. Two exceptions are the systolic murmur of HCM, which usually becomes much louder, and that of MVP,
which becomes longer and often louder. After release of the Valsalva, right-sided murmurs tend to return to baseline intensity earlier than left-sided murmurs.
Exercise
Murmurs caused by blood flow across normal or obstructed valves (e.g., PS and MS) become louder with both isotonic and isometric (handgrip) exercise.
Murmurs of MR, VSD, and AR also increase with handgrip exercise.
Positional changes
With standing, most murmurs diminish, 2 exceptions being the murmur of HCM, which becomes louder, and that of MVP, which lengthens and often is
intensified. With brisk squatting, most murmurs become louder, but those of HCM and MVP usually soften and may disappear. Passive leg raising usually
produces the same results as brisk squatting.
Postventricular premature beat or atrial fibrillation
Murmurs originating at normal or stenotic semilunar valves increase in intensity during the cardiac cycle after a VPB or in the beat after a long cycle length
in AF. By contrast, systolic murmurs due to atrioventricular valve regurgitation do not change, diminish (papillary muscle dysfunction), or become shorter
(MVP).
Pharmacological interventions
During the initial relative hypotension after amyl nitrite inhalation, murmurs of MR, VSD, and AR decrease, whereas murmurs of AS increase because of
increased stroke volume. During the later tachycardia phase, murmurs of MS and right-sided lesions also increase. This intervention may thus distinguish the
murmur of the Austin-Flint phenomenon from that of MS. The response in MVP often is biphasic (softer then louder than control).
Transient arterial occlusion
Transient external compression of both arms by bilateral cuff inflation to 20 mm Hg greater than peak systolic pressure augments the murmurs of MR, VSD,
and AR but not murmurs due to other causes.
AF indicates atrial fibrillation; AR, aortic regurgitation; AS, aortic stenosis; HCM, hypertrophic cardiomyopathy; MR, mitral regurgitation; MS, mitral stenosis; MVP,
mitral valve prolapse; PS, pulmonic stenosis; VPB, ventricular premature beat; and VSD, ventricular septal defect.
murmurs of aortic regurgitation (AR) or pulmonic regurgitation due to pulmonary hypertension are generally decrescendo, consistent with the rapid decline in volume or rate of
regurgitation during diastole. The diastolic murmur of pulmonic regurgitation without pulmonary hypertension is low
to medium pitched, and the onset of this murmur is slightly
delayed because regurgitant flow is minimal at pulmonic
valve closure, when the reverse pressure gradient responsible
for the regurgitation is minimal. Such murmurs are common
late after repair of tetralogy of Fallot.
Middiastolic murmurs usually originate from the mitral
and tricuspid valves, occur early during ventricular filling,
and are due to a relative disproportion between valve orifice
size and diastolic blood flow volume. Although they are
usually due to mitral or tricuspid stenosis, middiastolic
murmurs may also be due to increased diastolic blood flow
across the mitral or tricuspid valve when such valves are
severely regurgitant, across the normal mitral valve (MV) in
patients with ventricular septal defect or patent ductus arteriosus, and across the normal tricuspid valve in patients with
atrial septal defect. In severe, chronic AR, a low-pitched,
rumbling diastolic murmur (Austin-Flint murmur) is often
present at the LV apex; it may be either middiastolic or
presystolic. An opening snap is absent in isolated AR.
Presystolic murmurs begin during the period of ventricular
filling that follows atrial contraction and therefore occur in
sinus rhythm. They are usually due to mitral or tricuspid
stenosis. A right or left atrial myxoma may cause either
middiastolic or presystolic murmurs similar to tricuspid or
mitral stenosis (MS).
Continuous murmurs arise from high- to low-pressure
shunts that persist through the end of systole and the
beginning of diastole. Thus, they begin in systole, peak near
S2, and continue into all or part of diastole. There are many
causes of continuous murmurs, but they are uncommon in
patients with valvular heart disease.5–9
2.1.2.1. Dynamic Cardiac Auscultation
Attentive cardiac auscultation during dynamic changes in
cardiac hemodynamics often enables the observer to deduce
the correct origin and significance of a cardiac murmur.10 –13
Changes in the intensity of heart murmurs during various
maneuvers are indicated in Table 2.
2.1.2.2. Other Physical Findings
The presence of other physical findings, either cardiac or
noncardiac, may provide important clues to the significance of a
cardiac murmur and the need for further testing (Fig. 2). For
example, a right heart murmur in early to midsystole at the lower
left sternal border likely represents TR without pulmonary
hypertension in an injection drug user who presents with fever,
petechiae, Osler’s nodes, and Janeway lesions.
Associated cardiac findings frequently provide important
information about cardiac murmurs. Fixed splitting of the
second heart sound during inspiration and expiration in a
patient with a grade 2/6 midsystolic murmur in the pulmonic
area and left sternal border should suggest the possibility of
an atrial septal defect. A soft or absent A2 or reversed
splitting of S2 may denote severe AS. An early aortic systolic
ejection sound heard during inspiration and expiration suggests a bicuspid aortic valve, whereas an ejection sound heard
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Figure 2. Strategy for evaluating heart murmurs.
*If an electrocardiogram or chest X-ray has been obtained and is abnormal, echocardiography is indicated.
only in the pulmonic area and at the left sternal border during
expiration usually denotes pulmonic valve stenosis. LV
dilatation on precordial palpation and bibasilar pulmonary
rales favor the diagnosis of severe, chronic MR in a patient
with a grade 2/6 holosystolic murmur at the cardiac apex. A
slow-rising, diminished arterial pulse suggests severe AS in a
patient with a grade 2/6 midsystolic murmur at the second
right intercostal space. The typical parvus et tardus pulse may
be absent in the elderly, even in those with severe AS,
secondary to the effects of aging on the vasculature. Pulsus
parvus may also occur with severely reduced cardiac output
from any cause. Factors that aid in the differential diagnosis
of LV outflow tract obstruction are listed in Table 3.14
Examination of the jugular venous wave forms may provide
additional or corroborative information. For example, regurgitant cv waves are indicative of TR and are often present
without an audible murmur.
For example, symptoms of syncope, angina pectoris, or heart
failure in a patient with a midsystolic murmur will usually
result in a more aggressive diagnostic approach than in a
patient with a similar midsystolic murmur who has none of
these symptoms. An echocardiogram to rule in or rule out the
presence of significant AS should be obtained. A history of
thromboembolism will also usually result in a more extensive
workup. In patients with cardiac murmurs and clinical findings suggestive of endocarditis, echocardiography is
indicated.2
Conversely, many asymptomatic children and young adults
with grade 2/6 midsystolic murmurs and no other cardiac
physical findings need no further workup after the initial
history and physical examination (Fig. 2). A particularly
important group is the large number of asymptomatic older
patients, many with systemic hypertension, who have midsystolic murmurs, usually of grade 1 or 2 intensity, related to
sclerotic aortic valve leaflets; flow into tortuous, noncompliant great vessels; or a combination of these findings. Such
murmurs must be distinguished from those caused by more
2.1.2.3. Associated Symptoms
An important consideration in the patient with a cardiac
murmur is the presence or absence of symptoms15 (Fig. 2).
Table 3.
Factors That Differentiate the Various Causes of Left Ventricular Outflow Tract Obstruction
Factor
Valvular
Discrete
Subvalvular
Supravalvular
Obstructive
HCM
Valve calcification
Common after age 40 y
No
No
No
Dilated ascending aorta
Common after age 40 y
Rare
Rare
Rare
PP after VPB
Increased
Increased
Increased
Decreased
Valsalva effect on SM
Decreased
Decreased
Decreased
Increased
Murmur of AR
Common after age 40 y
Rare
Sometimes
No
Fourth heart sound (S4)
If severe
Uncommon
Uncommon
Common
Paradoxical splitting
Sometimes*
No
No
Rather common*
Ejection click
Most (unless valve calcified)
No
No
Uncommon or none
Maximal thrill and murmur
2nd RIS
1st RIS
2nd RIS
4th LIS
Carotid pulse
Normal to anacrotic* (parvus et tardus)
Unequal
Normal to anacrotic
Brisk, jerky, systolic rebound
*Depends on severity. Modified with permission from Marriott HJL. Bedside cardiac diagnosis. Philadelphia, Pa: Lippincott; 1993:116.
AR indicates aortic regurgitation; HCM, hypertrophic cardiomyopathy; LIS, left intercostal space; PP, pulse pressure; RIS, right intercostal space; SM, systolic
murmur; and VPB, ventricular premature beat.
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significant degrees of aortic valve thickening, calcification,
and reduced excursion that result in milder or greater degrees
of valvular AS. The absence of LV hypertrophy on the
electrocardiogram (ECG) may be reassuring, but echocardiography is frequently necessary. Aortic sclerosis can be
defined by focal areas of increased echogenicity and thickening of the leaflets without restriction of motion and a peak
velocity of less than 2.0 m per second. The recognition of
aortic valve sclerosis may prompt the initiation of more
aggressive programs of coronary heart disease prevention. In
patients with AS, it is difficult to assess the rate and severity
of disease progression on the basis of auscultatory findings
alone.
2.1.3. Electrocardiography and Chest Roentgenography
Although echocardiography usually provides more specific
and often quantitative information about the significance of a
heart murmur and may be the only test needed, the ECG and
chest X-ray are readily available and may have been obtained
previously. The absence of ventricular hypertrophy, atrial
enlargement, arrhythmias, conduction abnormalities, prior
myocardial infarction, and evidence of active ischemia on the
ECG provides useful negative information at a relatively low
cost. Abnormal ECG findings in a patient with a heart
murmur, such as ventricular hypertrophy or a prior infarction,
should lead to a more extensive evaluation that includes
echocardiography (Fig. 2).
Posteroanterior and lateral chest roentgenograms often
yield qualitative information on cardiac chamber size, pulmonary blood flow, pulmonary and systemic venous pressure,
and cardiac calcification in patients with cardiac murmurs.
When abnormal findings are present on chest X-ray, echocardiography should be performed (Fig. 2). A normal chest
X-ray and ECG are likely in asymptomatic patients with
isolated midsystolic murmurs, particularly in younger age
groups, when the murmur is grade 2 or less in intensity and
heard along the left sternal border.16 –18 Routine ECG and
chest radiography are not recommended in this setting.
2.1.4. Echocardiography
Class I
1. Echocardiography is recommended for asymptomatic
patients with diastolic murmurs, continuous murmurs,
holosystolic murmurs, late systolic murmurs, murmurs
associated with ejection clicks, or murmurs that radiate to the neck or back. (Level of Evidence: C)
2. Echocardiography is recommended for patients with
heart murmurs and symptoms or signs of heart failure,
myocardial ischemia/infarction, syncope, thromboembolism, infective endocarditis, or other clinical evidence of structural heart disease. (Level of Evidence: C)
3. Echocardiography is recommended for asymptomatic
patients who have grade 3 or louder midpeaking
systolic murmurs. (Level of Evidence: C)
Class IIa
1. Echocardiography can be useful for the evaluation of
asymptomatic patients with murmurs associated with
other abnormal cardiac physical findings or murmurs
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associated with an abnormal ECG or chest X-ray.
(Level of Evidence: C)
2. Echocardiography can be useful for patients whose
symptoms and/or signs are likely noncardiac in origin
but in whom a cardiac basis cannot be excluded by
standard evaluation. (Level of Evidence: C)
Class III
1. Echocardiography is not recommended for patients
who have a grade 2 or softer midsystolic murmur
identified as innocent or functional by an experienced
observer. (Level of Evidence: C)
Echocardiography with color flow and spectral Doppler
evaluation is an important noninvasive method for assessing
the significance of cardiac murmurs. Information regarding
valve morphology and function, chamber size, wall thickness,
ventricular function, pulmonary and hepatic vein flow, and
estimates of pulmonary artery pressures can be readily
integrated.
Although echocardiography can provide important information, such testing is not necessary for all patients with
cardiac murmurs and usually adds little but expense in the
evaluation of asymptomatic younger patients with short grade
1 to 2 midsystolic murmurs and otherwise normal physical
findings. At the other end of the spectrum are patients with
heart murmurs for whom transthoracic echocardiography
proves inadequate. Depending on the specific clinical circumstances, transesophageal echocardiography, cardiac magnetic
resonance, or cardiac catheterization may be indicated for
better characterization of the valvular lesion.
It is important to note that Doppler ultrasound devices are
very sensitive and may detect trace or mild valvular regurgitation through structurally normal tricuspid and pulmonic
valves in a large percentage of young, healthy subjects and
through normal left-sided valves (particularly the MV) in a
variable but lower percentage of patients.16,19 –22
General recommendations for performing echocardiography in patients with heart murmurs are provided. Of course,
individual exceptions to these indications may exist.
2.1.5. Cardiac Catheterization
Cardiac catheterization can provide important information
about the presence and severity of valvular obstruction,
valvular regurgitation, and intracardiac shunting. It is not
necessary in most patients with cardiac murmurs and normal
or diagnostic echocardiograms, but it provides additional
information for some patients in whom there is a discrepancy
between the echocardiographic and clinical findings. Indications for cardiac catheterization for hemodynamic assessment
of specific valve lesions are given in Section 3, “Specific
Valve Lesions,” in these guidelines. Specific indications for
coronary angiography to screen for the presence of CAD are
given in Section 10.2.
2.1.6. Exercise Testing
Exercise testing can provide valuable information in patients
with valvular heart disease, especially in those whose symptoms are difficult to assess. It can be combined with echocardiography, radionuclide angiography, and cardiac catheterization. It has a proven track record of safety, even among
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asymptomatic patients with severe AS. Exercise testing has
generally been underutilized in this patient population and
should constitute an important component of the evaluation
process.
2.1.7. Approach to the Patient
The evaluation of the patient with a heart murmur may vary
greatly depending on many of the considerations discussed
above.23,24 These include the timing of the murmur in the
cardiac cycle, its location and radiation, and its response to
various physiological maneuvers (Table 2). Also of importance
is the presence or absence of cardiac and noncardiac symptoms
and other findings on physical examination that suggest the
murmur is clinically significant (Fig. 2).
Patients with diastolic or continuous heart murmurs not
due to a cervical venous hum or a mammary souffle during
pregnancy are candidates for echocardiography. If the results
of echocardiography indicate significant heart disease, further
evaluation may be indicated. An echocardiographic examination is also recommended for patients with apical or left
sternal edge holosystolic or late systolic murmurs, for patients
with midsystolic murmurs of grade 3 or greater intensity, and
for patients with softer systolic murmurs in whom dynamic
cardiac auscultation suggests a definite diagnosis (e.g., hypertrophic cardiomyopathy).
Echocardiography is also recommended for patients in
whom the intensity of a systolic murmur increases during the
Valsalva maneuver, becomes louder when the patient assumes the upright position, and decreases in intensity when
the patient squats. These responses suggest the diagnosis of
either hypertrophic obstructive cardiomyopathy or MV prolapse (MVP). Additionally, further assessment is indicated
when a systolic murmur increases in intensity during transient
arterial occlusion, becomes louder during sustained handgrip
exercise, or does not increase in intensity either in the cardiac
cycle that follows a premature ventricular contraction or after
a long R-R interval in patients with atrial fibrillation. The
diagnosis of MR or ventricular septal defect in these circumstances is likely.
In many patients with grade 1 or 2 midsystolic murmurs, an
extensive workup is not necessary. This is particularly true
for children and young adults who are asymptomatic, have an
otherwise normal cardiac examination, and have no other
physical findings associated with cardiac disease.
However, echocardiography is indicated in certain patients
with grade 1 or 2 midsystolic murmurs, including patients
with symptoms or signs consistent with infective endocarditis, thromboembolism, heart failure, myocardial ischemia/
infarction, or syncope. Echocardiography also usually provides an accurate diagnosis in patients with other abnormal
physical findings, including widely split second heart sounds,
systolic ejection sounds, and specific changes in intensity of
the systolic murmur during certain physiological maneuvers
(Table 2).
Although echocardiography is an important test for patients with a moderate to high likelihood of a clinically
important cardiac murmur, it must be re-emphasized that
trivial, minimal, or physiological valvular regurgitation, especially affecting the mitral, tricuspid, or pulmonic valves, is
detected by color flow imaging techniques in many otherwise
normal patients, including many patients who have no heart
murmur at all.16,19 –22 This observation must be considered
when the results of echocardiography are used to guide
decisions in asymptomatic patients in whom echocardiography was used to assess the significance of an isolated
murmur.
Very few data address the cost-effectiveness of various
approaches to the patient undergoing medical evaluation of a
cardiac murmur. Optimal auscultation by well-trained examiners who can recognize an insignificant midsystolic murmur
with confidence (by dynamic cardiac auscultation as indicated) results in less frequent use of expensive additional
testing to define murmurs that do not indicate cardiac pathology.
Characteristics of innocent murmurs in asymptomatic adults
that have no functional significance include the following:
•
•
•
•
•
grade 1 to 2 intensity at the left sternal border
a systolic ejection pattern
normal intensity and splitting of the second heart sound
no other abnormal sounds or murmurs
no evidence of ventricular hypertrophy or dilatation and
the absence of increased murmur intensity with the Valsalva maneuver or with standing from a squatting
position.12
Such murmurs are especially common in high-output states
such as anemia and pregnancy.25,26 When the characteristic
features of individual murmurs are considered together with
information obtained from the history and physical examination, the correct diagnosis can usually be established.24 In
patients with ambiguous clinical findings, the echocardiogram can often provide a definite diagnosis, rendering a chest
X-ray and/or ECG unnecessary.
In the evaluation of heart murmurs, the purposes of
echocardiography are to
•
•
•
•
•
•
•
define the primary lesion in terms of cause and severity
define hemodynamics
define coexisting abnormalities
detect secondary lesions
evaluate cardiac chamber size and function
establish a reference point for future comparisons
re-evaluate the patient after an intervention.
Throughout these guidelines, treatment recommendations
will often derive from specific echocardiographic measurements of LV size and systolic function. Accuracy and
reproducibility are critical, particularly when applied to
surgical recommendations for asymptomatic patients with
MR or AR. Serial measurements over time, or reassessment
with a different imaging technology (radionuclide ventriculography or cardiac magnetic resonance), are often helpful for
counseling individual patients. Lastly, although handheld
echocardiography can be used for screening purposes, it is
important to note that its accuracy is highly dependent on the
experience of the user. The precise role of handheld echocardiography for the assessment of patients with valvular heart
disease has not been elucidated.
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As valuable as echocardiography may be, the basic cardiovascular physical examination is still the most appropriate
method of screening for cardiac disease and will establish
many clinical diagnoses. Echocardiography should not replace the cardiovascular examination but can be useful in
determining the cause and severity of valvular lesions,
particularly in older and/or symptomatic patients.
2.2. Valve Disease Severity Table
Classification of the severity of valve disease in adults is
listed in Table 4.27 The classification for regurgitant lesions is
adapted from the recommendations of the American Society
of Echocardiography.27 For full recommendations of the
American Society of Echocardiography, please refer to the
original document. Subsequent sections of the current guidelines refer to the criteria in Table 427 to define severe valvular
stenosis or regurgitation.
2.3. Endocarditis and Rheumatic Fever
Prophylaxis (UPDATED)
This updated section deals exclusively with the changes in
recommendations for antibiotic prophylaxis against infective
endocarditis in patients with valvular heart disease. Treatment
considerations in patients with congenital heart disease
(CHD) or implanted cardiac devices are reviewed in detail in
other publications1071 and the upcoming ACC/AHA guideline
for the management of adult patients with CHD.1072 For an
in-depth review of the rationale for the recommended
changes in the approach to patients with valvular heart
disease, the reader is referred to the AHA guidelines on
prevention of infective endocarditis, published online April
2007.1070
2.3.1. Endocarditis Prophylaxis (UPDATED)
Class IIa
1. Prophylaxis against infective endocarditis is reasonable for the following patients at highest risk for
adverse outcomes from infective endocarditis who undergo dental procedures that involve manipulation of
either gingival tissue or the periapical region of teeth
or perforation of the oral mucosa1070:
● Patients with prosthetic cardiac valve or prosthetic
material used for cardiac valve repair. (Level of
Evidence: B)
● Patients with previous infective endocarditis. (Level of
Evidence: B)
● Patients with CHD. (Level of Evidence: B)
● Unrepaired cyanotic CHD, including palliative
shunts and conduits. (Level of Evidence: B)
● Completely repaired congenital heart defect repaired with prosthetic material or device,
whether placed by surgery or by catheter intervention, during the first 6 months after the procedure. (Level of Evidence: B)
● Repaired CHD with residual defects at the site or
adjacent to the site of a prosthetic patch or
prosthetic device (both of which inhibit endothelialization). (Level of Evidence: B)
●
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Cardiac transplant recipients with valve regurgitation due to a structurally abnormal valve. (Level of
Evidence: C)
Class III
1. Prophylaxis against infective endocarditis is not recommended for nondental procedures (such as transesophageal echocardiogram, esophagogastroduodenoscopy, or
colonoscopy) in the absence of active infection. (Level of
Evidence: B)1070
(Table 5 of the 2006 Valvular Heart Disease Guideline1068 is
now obsolete.)
Infective endocarditis is a serious illness associated with
significant morbidity and mortality. Its prevention by the
appropriate administration of antibiotics before a procedure
expected to produce bacteremia merits serious consideration.
Experimental studies have suggested that endothelial damage
leads to platelet and fibrin deposition and the formation of
nonbacterial thrombotic endocardial lesions. In the presence
of bacteremia, organisms may adhere to these lesions and
multiply within the platelet-fibrin complex, leading to an
infective vegetation. Valvular and congenital abnormalities, especially those associated with high velocity jets, can
result in endothelial damage, platelet fibrin deposition, and
a predisposition to bacterial colonization. Since 1955, the
AHA has made recommendations for prevention of infective endocarditis with antimicrobial prophylaxis before
specific dental, gastrointestinal (GI), and genitourinary
(GU) procedures in patients at risk for its development.
However, many authorities and societies, as well as the
conclusions of published studies, have questioned the
efficacy of antimicrobial prophylaxis in most situations.
On the basis of these concerns, a writing group was
appointed by the AHA for their expertise in prevention and
treatment of infective endocarditis, with liaison members
representing the American Dental Association, the Infectious
Disease Society of America, and the American Academy of
Pediatrics. The writing group reviewed the relevant literature
regarding procedure-related bacteremia and infective endocarditis, in vitro susceptibility data of the most common
organisms that cause infective endocarditis, results of prophylactic studies of animal models of infective endocarditis,
and both retrospective and prospective studies of prevention
of infective endocarditis. As a result, major changes were
made in the recommendations for prophylaxis against infective endocarditis.
The major changes in the updated recommendations included the following:
• The committee concluded that only an extremely small
number of cases of infective endocarditis might be prevented by antibiotic prophylaxis for dental procedures
even if such prophylactic therapy were 100 percent effective.
• Infective endocarditis prophylaxis for dental procedures is
reasonable only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome
from infective endocarditis.
• For patients with these underlying cardiac conditions,
prophylaxis is reasonable for all dental procedures that
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Table 4.
Classification of the Severity of Valve Disease in Adults
A. Left-sided valve disease
Aortic Stenosis
Indicator
Mild
Jet velocity (m per s)
Less than 3.0
Moderate
Severe
3.0–4.0
Greater than 4.0
Mean gradient (mm Hg)*
Less than 25
25–40
Greater than 40
Valve area (cm2)
Greater than 1.5
1.0–1.5
Less than 1.0
Valve area index (cm2 per m2)
Less than 0.6
Mitral Stenosis
Mild
Moderate
Severe
Mean gradient (mm Hg)*
Less than 5
5–10
Greater than 10
Pulmonary artery systolic pressure (mm Hg)
Less than 30
30–50
Greater than 50
Valve area (cm2)
Greater than 1.5
1.0–1.5
Less than 1.0
Aortic Regurgitation
Mild
Moderate
Severe
Qualitative
Angiographic grade
1⫹
2⫹
3–4⫹
Color Doppler jet width
Central jet, width less
than 25% of LVOT
Greater than mild but no
signs of severe AR
Central jet, width greater than 65% LVOT
Doppler vena contracta width (cm)
Less than 0.3
0.3–0.6
Greater than 0.6
Quantitative (cath or echo)
Regurgitant volume (ml per beat)
Less than 30
30–59
Greater than or equal to 60
Regurgitant fraction (%)
Less than 30
30–49
Greater than or equal to 50
Regurgitant orifice area (cm2)
Less than 0.10
0.10–0.29
Greater than or equal to 0.30
Additional essential criteria
Left ventricular size
Increased
Mitral Regurgitation
Mild
Moderate
Severe
Angiographic grade
1⫹
2⫹
3–4⫹
Color Doppler jet area
Small, central jet (less
than 4 cm2 or less than
20% LA area)
Signs of MR greater than
mild present but no
criteria for severe MR
Vena contracta width greater than 0.7 cm with large
central MR jet (area greater than 40% of LA area)
or with a wall-impinging jet of any size, swirling in
LA
Doppler vena contracta width (cm)
Less than 0.3
0.3–0.69
Greater than or equal to 0.70
Regurgitant volume (ml per beat)
Less than 30
30–59
Greater than or equal to 60
Regurgitant fraction (%)
Less than 30
30–49
Greater than or equal to 50
Less than 0.20
0.20–0.39
Greater than or equal to 0.40
Qualitative
Quantitative (cath or echo)
2
Regurgitant orifice area (cm )
Additional essential criteria
Left atrial size
Enlarged
Left ventricular size
Enlarged
B. Right-sided valve disease
Characteristic
Severe tricuspid stenosis:
Valve area less than 1.0 cm2
Severe tricuspid regurgitation:
Vena contracta width greater than 0.7 cm and systolic flow reversal in hepatic veins
Severe pulmonic stenosis:
Jet velocity greater than 4 m per s or maximum gradient greater than 60 mm Hg
Severe pulmonic regurgitation:
Color jet fills outflow tract; dense continuous wave Doppler signal with a steep deceleration slope
*Valve gradients are flow dependent and when used as estimates of severity of valve stenosis should be assessed with knowledge of cardiac output or forward
flow across the valve. Modified from the Journal of the American Society of Echocardiography, 16, Zoghbi WA, Recommendations for evaluation of the severity of
native valvular regurgitation with two-dimensional and Doppler echocardiography, 777– 802, Copyright 2003, with permission from American Society of
Echocardiography.27
AR indicates aortic regurgitation; cath, catheterization; echo, echocardiography; LA, left atrial/atrium; LVOT, left ventricular outflow tract; and MR, mitral
regurgitation.
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Bonow et al
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
• Maintenance of optimal oral health and hygiene may
reduce the incidence of bacteremia from daily activities
and is more important than prophylactic antibiotics for a
dental procedure to reduce the risk of infective
endocarditis.
Table 6. Endocarditis Prophylaxis for Dental Procedures
(UPDATED)*
Reasonable
Not Recommended
Endocarditis prophylaxis is
reasonable for patients
with the highest risk of
adverse outcomes who
undergo dental
procedures that involve
manipulation of either
gingival tissue or the
periapical region of
teeth or perforation of
the oral mucosa.
Endocarditis prophylaxis is not
recommended for:
• Routine anesthetic injections through
noninfected tissue
• Dental radiographs
• Placement or removal of prosthodontic
or orthodontic appliances
• Adjustment of orthodontic appliances
• Placement of orthodontic brackets
• Shedding of deciduous teeth
• Bleeding from trauma to the lips or
oral mucosa
(Table 8 of the 2006 Valvular Heart Disease Guidelines1068 is
now obsolete.)
The AHA Prevention of Infective Endocarditis Committee
recommended that prophylaxis should be given only to the
high-risk group of patients prior to dental procedures that
involve manipulation of gingival tissue or the periapical
region of the teeth or perforation of oral mucosa. High-risk
patients were defined as those patients with underlying
cardiac conditions associated with the highest risk of adverse
outcome from infective endocarditis, not necessarily those
with an increased lifetime risk of acquisition of infective
endocarditis. Prophylaxis is no longer recommended for
prevention of endocarditis for procedures involving the respiratory tract unless the procedure is performed in a highrisk patient and involves incision of the respiratory tract
mucosa, such as tonsillectomy and adenoidectomy. Prophylaxis is no longer recommended for prevention of infective
endocarditis for GI or GU procedures, including diagnostic
esophagogastroduodenoscopy or colonoscopy. However, in
high-risk patients with infections of the GI or GU tract, it is
reasonable to administer antibiotic therapy to prevent wound
infection or sepsis. For high-risk patients undergoing elective
cystoscopy or other urinary tract manipulation who have
enterococcal urinary tract infection or colonization, antibiotic
therapy to eradicate enterococci from the urine before the
procedure is reasonable.
These changes are a significant departure from the past
AHA723 and European Society of Cardiology1073 recommendations for prevention of infective endocarditis, and may
violate long-standing expectations in practice patterns of
*This table corresponds to Table 3 in the ACC/AHA 2008 Guideline Update on
Valvular Heart Disease: Focused Update on Infective Endocarditis.1069
Adapted with permission.28
involve manipulation of either gingival tissue or the
periapical region of teeth or perforation of oral mucosa.
• Prophylaxis is not recommended based solely on an increased
lifetime risk of acquisition of infective endocarditis.
• Administration of antibiotics solely to prevent endocarditis
is not recommended for patients who undergo GU or GI
tract procedure.
The rationale for these revisions is based on the following:
• Infective endocarditis is more likely to result from frequent
exposure to random bacteremias associated with daily
activities than from bacteremia caused by a dental, GI
tract, or GU procedure;
• Prophylaxis may prevent an exceedingly small number of
cases of infective endocarditis (if any) in individuals who
undergo a dental, GI tract, or GU procedure;
• The risk of antibiotic associated adverse effects exceeds
the benefit (if any) from prophylactic antibiotic therapy;
Table 7.
e537
Regimens for a Dental Procedure (UPDATED)*
Regimen: Single Dose 30 to 60 min
Before Procedure
Situation
Oral
Unable to take oral medication
Agent
Adults
Children
Amoxicillin
2g
50 mg/kg
Ampicillin
2 g IM or IV
50 mg/kg IM or IV
Cefazolin or ceftriaxone
1 g IM or IV
50 mg/kg IM or IV
Cephalexin†‡
2g
50 mg/kg
600 mg
20 mg/kg
OR
Allergic to penicillins or ampicillin—oral
OR
Clindamycin
OR
Allergic to penicillins or ampicillin and unable to take oral medication
Azithromycin or clarithromycin
500 mg
15 mg/kg
Cefazolin or ceftriaxone‡
1 g IM or IV
50 mg/kg IM or IV
600 mg IM or IV
20 mg/kg IM or IV
OR
Clindamycin
*This table corresponds to Table 4 in the ACC/AHA 2008 Guideline Update on Valvular Heart Disease: Focused Update on Infective Endocarditis.1069
†Or use other first- or second-generation oral cephalosporin in equivalent adult or pediatric dosage.
‡Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin.
IM indicates intramuscular; and IV, intravenous.
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patients and healthcare providers. However, the writing
committee for these updated guidelines consisted of experts
in the field of infective endocarditis; input was also obtained
from experts not affiliated with the writing group. All data to
date were thoroughly reviewed, and the current recommendations reflect analysis of all relevant literature. This multidisciplinary team of experts emphasized that previous published guidelines for the prevention of endocarditis contained
ambiguities and inconsistencies and relied more on opinion
than on data. The writing committee delineated the reasons
for which evolutionary refinement in the approach to infective endocarditis prophylaxis can be justified. In determining
which patients receive prophylaxis, there is a clear focus on
the risk of adverse outcomes after infective endocarditis
rather than the lifetime risk of acquisition of infective
endocarditis. The current recommendations result in greater
clarity for patients, health care providers, and consulting
professionals.
Other international societies have published recommendations and guidelines for the prevention of infective endocarditis. New recommendations from the British Society for
Antimicrobial Chemotherapy are similar to the current AHA
recommendations for prophylaxis before dental procedures.
The British Society for Antimicrobial Chemotherapy did
differ in continuing to recommend prophylaxis for high-risk
patients prior to GI or GU procedures associated with
bacteremia or endocarditis.1074
Therefore, Class IIa indications for prophylaxis against
infective endocarditis are reasonable for valvular heart
disease patients at highest risk for adverse outcomes from
infective endocarditis before dental procedures that involve manipulation of either gingival tissue. This high-risk
group includes: 1) patients with a prosthetic heart valve or
prosthetic material used for valve repair, 2) patients with a
past history of infective endocarditis, and 3) patients with
cardiac valvulopathy following cardiac transplantation, as
well as 4) specific patients with CHD. Patients with
innocent murmurs and those patients who have abnormal
echocardiographic findings without an audible murmur
should definitely not be given prophylaxis for infective
endocarditis. Infective endocarditis prophylaxis is not
necessary for nondental procedures which do not penetrate
the mucosa, such as transesophageal echocardiography,
diagnostic bronchoscopy, esophagogastroscopy, or
colonoscopy, in the absence of active infection.
The committee recognizes that decades of previous
recommendations for patients with most forms of valvular heart disease and other conditions have been abruptly
changed by the new AHA guidelines.1069 Because this may
cause consternation among patients, clinicians should be
available to discuss the rationale for these new changes
with their patients, including the lack of scientific evidence to demonstrate a proven benefit for infective endocarditis prophylaxis. In select circumstances, the committee also understands that some clinicians and some
patients may still feel more comfortable continuing with
prophylaxis for infective endocarditis, particularly for
those with bicuspid aortic valve or coarctation of the
aorta, severe mitral valve prolapse, or hypertrophic ob-
structive cardiomyopathy. In those settings, the clinician
should determine that the risks associated with antibiotics
are low before continuing a prophylaxis regimen. Over
time, and with continuing education, the committee anticipates increasing acceptance of the new guidelines
among both provider and patient communities.
A multicenter randomized controlled trial has never been
performed to evaluate the efficacy of infective endocarditis
prophylaxis in patients who undergo dental, GI, or GU
procedures. On the basis of these new recommendations,
fewer patients will receive infective endocarditis prophylaxis.
It is hoped that the revised recommendations will stimulate
properly designed prospective studies on the prevention of
infective endocarditis.
2.3.2. Rheumatic Fever Prophylaxis
2.3.2.1. General Considerations
Rheumatic fever is an important cause of valvular heart
disease. In the United States (and Western Europe), cases of
acute rheumatic fever have been uncommon since the 1970s.
However, starting in 1987, an increase in cases has been
observed.43,44 With the enhanced understanding of the causative organism, group A beta hemolytic streptococcus, its
rheumatogenicity is attributed to the prevalence of M-protein
serotypes of the offending organism. This finding has resulted
in the development of kits that allow rapid detection of group
A streptococci with specificity greater than 95% and more
rapid identification of their presence in upper respiratory
infection. Because the test has a low sensitivity, a negative
test requires throat culture confirmation.44 Prompt recognition
and treatment comprise primary rheumatic fever prevention.
For patients who have had a previous episode of rheumatic
fever, continuous antistreptococcal prophylaxis is indicated
for secondary prevention.
2.3.2.2. Primary Prevention
Rheumatic fever prevention and treatment guidelines have
been established previously by the AHA (Table 9).45
2.3.2.3. Secondary Prevention
Class I
1. Patients who have had rheumatic fever with or without
carditis (including patients with MS) should receive
prophylaxis for recurrent rheumatic fever. (Level of
Evidence: B)
Patients who have had an episode of rheumatic fever are at
high risk of developing recurrent episodes of acute rheumatic
fever. Patients who develop carditis are especially prone to
similar episodes with subsequent attacks. Secondary prevention of rheumatic fever recurrence is thus of great importance.
Continuous antimicrobial prophylaxis has been shown to be
effective. Anyone who has had rheumatic fever with or
without carditis (including patients with MS) should receive
prophylaxis for recurrent rheumatic fever. The 1995 AHA
guidelines for secondary prevention are shown in Table 10,
and the 1995 AHA guidelines for duration of secondary
prevention are shown in Table 11.45
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Bonow et al
Table 9.
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
e539
Primary Prevention of Rheumatic Fever
Agent
Dose
Benzathine/Penicillin G
Mode
Patients 27 kg (60 lb) or less: 600 000 U
Duration
Intramuscular
Once
Oral
10 d
Oral
10 d
Oral
10 d
Oral
5d
Patients greater than 27 kg (60 lb): 1 200 000 U
or
Penicillin V (phenoxymethyl penicillin)
Children: 250 mg 2–3 times daily
Adolescents and adults: 500 mg 2–3 times daily
For individuals allergic to penicillin
Erythromycin
Estolate
20–40 mg per kg per day
2–4 times daily (maximum 1 g per day)
or
Ethylsuccinate
40 mg per kg per day
2–4 times daily (maximum 1 g per day)
or
Azithromycin
500 mg on first day
250 mg per day for the next 4 days
Reprinted with permission from Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement
for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American
Heart Association. Pediatrics 1995;96:758 – 64.45
3. Specific Valve Lesions
3.1. Aortic Stenosis
3.1.1. Introduction
The most common cause of AS in adults is calcification of a
normal trileaflet or congenital bicuspid valve.46 – 49 This calcific disease progresses from the base of the cusps to the
leaflets, eventually causing a reduction in leaflet motion and
effective valve area without commissural fusion. Calcific AS
is an active disease process characterized by lipid accumulaTable 10.
Secondary Prevention of Rheumatic Fever
Agent
Dose
Mode
Penicillin G benzathine
1 200 000 U every 4 wk
(every 3 wk for high-risk*
pts such as those with
residual carditis)
Intramuscular
250 mg twice daily
Oral
0.5 g once daily for pts
27 g (60 lb) or less;
1.0 g once daily for pts
greater than 27 kg (60 lb)
Oral
250 mg twice daily
Oral
tion, inflammation, and calcification, with many similarities
to atherosclerosis.50 – 60 Rheumatic AS due to fusion of the
commissures with scarring and eventual calcification of the
cusps is less common and is invariably accompanied by MV
disease. A congenital malformation of the valve may also
result in stenosis and is the more common cause in young
adults. The management of congenital AS in adolescents and
young adults is discussed in Section 6.1.
3.1.1.1. Grading the Degree of Stenosis
Although AS is best described as a disease continuum, and
there is no single value that defines severity, for these
guidelines, we graded AS severity on the basis of a variety of
hemodynamic and natural history data (Table 4),27,61 using
definitions of aortic jet velocity, mean pressure gradient, and
valve area as follows:
or
Penicillin V
Table 11.
Duration of Secondary Rheumatic Fever Prophylaxis
Category
or
Sulfadiazine
For individuals allergic
to penicillin and
sulfadiazine
Erythromycin
*High-risk patients include patients with residual rheumatic carditis and
patients from economically disadvantaged populations. Dajani A, Taubert K,
Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of
rheumatic fever: a statement for health professionals. Committee on Rheumatic
Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular
Disease in the Young, the American Heart Association. Pediatrics 1995;96:
758 – 64.45
Pts indicates patients.
Duration
Rheumatic fever with carditis and
residual heart disease
(persistent valvular disease)
10 y or greater since last episode and
at least until age 40 y; sometimes
lifelong prophylaxis*
Rheumatic fever with carditis but
no residual heart disease (no
valvular disease)
10 y or well into adulthood, whichever
is longer
Rheumatic fever without carditis
5 y or until age 21 y, whichever is
longer
*The committee’s interpretation of “lifelong” prophylaxis refers to patients
who are at high risk and likely to come in contact with populations with a high
prevalence of streptococcal infection, that is, teachers and day-care workers.
Reprinted with permission from Dajani A, Taubert K, Ferrieri P, et al. Treatment
of acute streptococcal pharyngitis and prevention of rheumatic fever: a
statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the
Young, the American Heart Association. Pediatrics 1995;96:758 – 64.45
Downloaded from http://circ.ahajournals.org/ by guest on September 9, 2014
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October 7, 2008
• Mild (area 1.5 cm2, mean gradient less than 25 mm Hg, or
jet velocity less than 3.0 m per second)
• Moderate (area 1.0 to 1.5 cm2, mean gradient 25 to 40 mm
Hg, or jet velocity 3.0 to 4.0 m per second)
• Severe (area less than 1.0 cm2, mean gradient greater than
40 mm Hg, or jet velocity greater than 4.0 m per second).
When stenosis is severe and cardiac output is normal, the
mean transvalvular pressure gradient is generally greater than
40 mm Hg. However, when cardiac output is low, severe
stenosis may be present with a lower transvalvular gradient
and velocity, as discussed below. Some patients with severe
AS remain asymptomatic, whereas others with only moderate
stenosis develop symptoms. Therapeutic decisions, particularly
those related to corrective surgery, are based largely on the
presence or absence of symptoms. Thus, the absolute valve area
(or transvalvular pressure gradient) is not the primary determinant of the need for aortic valve replacement (AVR).
3.1.2. Pathophysiology
In adults with AS, the obstruction develops gradually—
usually over decades. During this time, the left ventricle
adapts to the systolic pressure overload through a hypertrophic process that results in increased LV wall thickness, while
a normal chamber volume is maintained.62– 64 The resulting
increase in relative wall thickness is usually enough to
counter the high intracavitary systolic pressure, and as a
result, LV systolic wall stress (afterload) remains within the
range of normal. The inverse relation between systolic wall
stress and ejection fraction is maintained; as long as wall
stress is normal, the ejection fraction is preserved.65 However,
if the hypertrophic process is inadequate and relative wall
thickness does not increase in proportion to pressure, wall
stress increases and the high afterload causes a decrease in
ejection fraction.65– 67 Depressed contractile state of the myocardium may also be responsible for a low ejection fraction,
and it is often difficult clinically to determine whether a low
ejection fraction is due to depressed contractility or to
excessive afterload.68 When low ejection fraction is caused by
depressed contractility, corrective surgery will be less beneficial than in patients with a low ejection fraction caused by
high afterload.69
As a result of increased wall thickness, low volume/mass
ratio, and diminished compliance of the chamber, LV enddiastolic pressure increases without chamber dilatation.70 –72
Thus, increased end-diastolic pressure usually reflects diastolic dysfunction rather than systolic dysfunction or failure.73
A forceful atrial contraction that contributes to an elevated
end-diastolic pressure plays an important role in ventricular
filling without increasing mean left atrial or pulmonary
venous pressure.74 Loss of atrial contraction such as that
which occurs with atrial fibrillation is often followed by
serious clinical deterioration.
The development of concentric hypertrophy appears to be
an appropriate and beneficial adaptation to compensate for
high intracavitary pressures. Unfortunately, this adaptation
often carries adverse consequences. The hypertrophied heart
may have reduced coronary blood flow per gram of muscle
and also exhibit a limited coronary vasodilator reserve, even
in the absence of epicardial CAD.75–77 The hemodynamic
stress of exercise or tachycardia can produce a maldistribution of coronary blood flow and subendocardial ischemia,
which can contribute to systolic or diastolic dysfunction of
the left ventricle. Hypertrophied hearts also exhibit an increased sensitivity to ischemic injury, with larger infarcts and
higher mortality rates than are seen in the absence of
hypertrophy.78 – 80 Another problem that is particularly common in elderly patients, especially women, is an excessive or
inappropriate degree of hypertrophy; wall thickness is greater
than necessary to counterbalance the high intracavitary pressures.81– 84 As a result, systolic wall stress is low and ejection
fraction is high; such inappropriate LV hypertrophy has been
associated with high perioperative morbidity and mortality.81,83
3.1.3. Natural History
The natural history of AS in the adult consists of a prolonged
latent period during which morbidity and mortality are very
low. The rate of progression of the stenotic lesion has been
estimated in a variety of invasive and noninvasive studies.85
Once even moderate stenosis is present (jet velocity greater
than 3.0 m per second) (Table 4),27 the average rate of
progression is an increase in jet velocity of 0.3 m per second
per year, an increase in mean pressure gradient of 7 mm Hg
per year, and a decrease in valve area of 0.1 cm2 per year.86 –96
However, there is marked individual variability in the rate of
hemodynamic progression. Although it appears that the
progression of AS can be more rapid in patients with
degenerative calcific disease than in those with congenital or
rheumatic disease,96 –98 it is not possible to predict the rate of
progression in an individual patient. For this reason, regular
clinical follow-up is mandatory in all patients with asymptomatic mild to moderate AS. In addition, progression to AS
may occur in patients with aortic sclerosis, defined as valve
thickening without obstruction to ventricular outflow.99
Aortic sclerosis, defined as irregular valve thickening
without obstruction to LV outflow, is present in about 25% of
adults over 65 years of age and is associated with clinical
factors such as age, sex, hypertension, smoking, serum
low-density lipoprotein and lipoprotein(a) levels, and diabetes mellitus.100 In the Cardiovascular Health Study, the
presence of aortic sclerosis on echocardiography in subjects
without known coronary disease was also associated with
adverse clinical outcome, with an approximately 50% increased risk of myocardial infarction and cardiovascular death
compared with subjects with a normal aortic valve.101 This has
been confirmed in 2 additional studies.102,103 The association
between aortic sclerosis and adverse cardiovascular outcomes
persisted even when age, sex, known cardiovascular disease, and
cardiovascular risk factors were taken into account. However,
the mechanism of this association is unclear and is unlikely to be
related to valve hemodynamics. Studies are in progress to
evaluate potential mechanisms of this association, including
subclinical atherosclerosis, endothelial dysfunction, and systemic inflammation.
In most patients with severe AS, impaired platelet function
and decreased levels of von Willebrand factor can be demonstrated. The severity of the coagulation abnormality correlates
with the severity of AS and resolves after valve replacement,
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Table 12.
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
e541
Clinical Outcomes in Prospective Studies of Asymptomatic Aortic Stenosis in Adults
Study, Year
Kelly et al., 1988109
No. of
Patients
51
Pellikka et al., 1990114
113
Kennedy et al., 1991115
66
Otto et al., 199761
123
Severity of Aortic
Stenosis
Vmax greater than
3.6 m per second
Vmax 4.0 m per second
or greater
Event-Free
Survival Without
Symptoms
Age, y
Mean
Follow-Up
63 ⫾ 8
5–25 mo
Overall
59% at 15 mo
40–94
20 mo
Overall
Overall
86% at 1 y
62% at 2 y
Group
AVA 0.7–1.2 cm2
67 ⫾ 10
35 mo
Overall
59% at 4 y
Vmax greater than
2.6 m per second
63 ⫾ 16
2.5 ⫾ 1.4 y
Overall
93 ⫾ 5% at 1 y
62 ⫾ 8% at 3 y
26 ⫾ 10% at 5 y
Subgroups:
Rosenhek et al., 200096
128
Vmax greater than
4.0 m per second
60 ⫾ 18
22 ⫾ 18 mo
Vmax less than 3–4 m per second
84 ⫾ 16% at 2 y
Vmax 3–4 m per second
66 ⫾ 13% at 2 y
Vmax greater than 3 m per
second
21 ⫾ 18% at 2 y
67 ⫾ 5% at 1 y
56 ⫾ 55% at 2 y
33 ⫾ 5% at 4 y
Overall
Subgroups:
75 ⫾ 9% at 4 y
No or mild Ca2⫹
2⫹
Moderate-severe Ca
Amato et al., 2001117
66
AVA 1.0 cm2 or
greater
18–80
(50 ⫾ 15)
15 ⫾ 12 mo
Overall
20 ⫾ 5% at 4 y
57% at 1 y
38% at 2 y
Subgroups:
AVA 0.7 cm2 or greater
AVA less than 0.7 cm
Das et al., 2005118
Pellikka et al., 2005116
125
622
AVA less than 1.4 cm2
Vmax 4.0 m per second
or greater
56–74
(mean 65)
72 ⫾ 11
12 mo
5.4 ⫾ 4.0 y
2
72% at 2 y
21% at 2 y
Negative exercise test
85% at 2 y
Positive exercise test*
19% at 2 y
Subgroups:
AVA 1.2 cm2 or greater
AVA 0.8 cm2 or less
100% at 1 y
46% at 1 y
No symptoms on exercise test
89% at 1 y
Symptoms on exercise test
49% at 1 y
Overall
82% at 1 y
67% at 2 y
33% at 5 y
*Positive exercise test indicates symptoms, abnormal ST-segment response, or abnormal blood pressure response (less than 20-mm Hg increase) with exercise.
AVA indicates aortic valve area; Ca2⫹, aortic valve calcification; and Vmax, peak instantaneous velocity.
except when the prosthetic valve area is small for patient size
(less than 0.8 cm2 per m2). This acquired von Willebrand
syndrome is associated with clinical bleeding, most often epistaxis or ecchymoses, in approximately 20% of patients.104
Eventually, symptoms of angina, syncope, or heart failure
develop after a long latent period, and the outlook changes
dramatically. After the onset of symptoms, average survival
is 2 to 3 years,105–111 with a high risk of sudden death. Thus,
the development of symptoms identifies a critical point in the
natural history of AS. Management decisions are based
largely on these data; most clinicians treat asymptomatic
patients conservatively, whereas corrective surgery is generally recommended in patients with symptoms thought to be
due to AS. It is important to emphasize that symptoms may be
subtle and often are not elicited by the physician in taking a
routine clinical history.
Sudden death is known to occur in patients with severe AS
and, in older retrospective studies, has been reported to occur
without prior symptoms.105,108,112,113 However, in prospective
echocardiographic studies, sudden death in previously
asymptomatic patients is rare.61,96,109,114 –116 Therefore, although sudden death may occur in the absence of preceding
symptoms in patients with AS,105,108,112,113,116 it is an uncommon event, estimated at less than 1% per year when patients
with known AS are followed up prospectively.
3.1.4. Management of the Asymptomatic Patient
Asymptomatic patients with AS have outcomes similar to
age-matched normal adults. However, disease progression
with symptom onset is common, as detailed in Table
12.61,96,109,114 –118 In a prospective study of 123 asymptomatic
adults with an initial jet velocity of at least 2.6 m per second,
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the rate of symptom development was 38% at 3 years for the
total group. However, clinical outcome was strongly dependent on AS severity, with an event-free survival of 84% at 2
years in those with a jet velocity less than 3 m per second
compared with only 21% in those with a jet velocity more
than 4 m per second.61,98 In another study of 128 asymptomatic adults with an initial aortic jet velocity of at least 4 m per
second, event-free survival was 67% at 1 year and 33% at 4
years, with predictors of outcome that included age and the
degree of valve calcification.96 A third study of patients with
aortic jet velocities greater than 4 m per second provided
similar results, with 33% remaining asymptomatic without
surgery at 5 years.116 Therefore, patients with asymptomatic
AS require frequent monitoring for development of symptoms and progressive disease.
3.1.4.1. Echocardiography (Imaging, Spectral, and Color
Doppler) in Aortic Stenosis
Class I
1. Echocardiography is recommended for the diagnosis
and assessment of AS severity. (Level of Evidence: B)
2. Echocardiography is recommended in patients with AS
for the assessment of LV wall thickness, size, and
function. (Level of Evidence: B)
3. Echocardiography is recommended for re-evaluation of
patients with known AS and changing symptoms or signs.
(Level of Evidence: B)
4. Echocardiography is recommended for the assessment
of changes in hemodynamic severity and LV function
in patients with known AS during pregnancy. (Level of
Evidence: B)
5. Transthoracic echocardiography is recommended for
re-evaluation of asymptomatic patients: every year for
severe AS; every 1 to 2 years for moderate AS; and
every 3 to 5 years for mild AS. (Level of Evidence: B)
Aortic stenosis typically is first suspected on the basis of the
finding of a systolic ejection murmur on cardiac auscultation;
however, physical examination findings are specific but not
sensitive for the diagnosis of AS severity.119 The classic
findings of a loud (grade 4/6), late-peaking systolic murmur
that radiates to the carotids, a single or paradoxically split
second heart sound (S2), and a delayed and diminished
carotid upstroke confirm the presence of severe AS. However, in the elderly, the carotid upstroke may be normal
because of the effects of aging on the vasculature, and the
murmur may be soft or may radiate to the apex. The only
physical examination finding that is reliable in excluding the
possibility of severe AS is a normally split second heart
sound.119
Echocardiography is indicated when there is a systolic
murmur that is grade 3/6 or greater, a single S2, or symptoms
that might be due to AS. The 2-dimensional (2D) echocardiogram is valuable for evaluation of valve anatomy and
function and determining the LV response to pressure overload. In nearly all patients, the severity of the stenotic lesion
can be defined with Doppler echocardiographic measurements of maximum jet velocity, mean transvalvular pressure
gradient, and continuity equation valve area, as discussed in
the “ACC/AHA/ASE 2003 Guidelines for the Clinical Application of Echocardiography.”2 Doppler evaluation of AS
severity requires attention to technical details, with the most
common error being underestimation of disease severity due
to a nonparallel intercept angle between the ultrasound beam
and high-velocity jet through the narrowed valve. When
measurement of LV outflow tract diameter is problematic,
the ratio of outflow tract velocity to aortic jet velocity can
be substituted for valve area, because this ratio is, in effect,
indexed for body size. A ratio of 0.9 to 1.0 is normal, with
a ratio less than 0.25 indicating severe stenosis. Echocardiography is also used to assess LV size and function,
degree of hypertrophy, and presence of other associated
valvular disease.
In some patients, it may be necessary to proceed with
cardiac catheterization and coronary angiography at the time
of initial evaluation. For example, this is appropriate if there
is a discrepancy between clinical and echocardiographic
examinations or if symptoms might be due to CAD.
3.1.4.2. Exercise Testing
Class IIb
1. Exercise testing in asymptomatic patients with AS may
be considered to elicit exercise-induced symptoms and
abnormal blood pressure responses. (Level of Evidence: B)
Class III
1. Exercise testing should not be performed in symptomatic patients with AS. (Level of Evidence: B)
Exercise testing in adults with AS has poor diagnostic
accuracy for evaluation of concurrent CAD. Presumably, this
is due to the presence of an abnormal baseline ECG, LV
hypertrophy, and limited coronary flow reserve. Electrocardiographic ST depression during exercise occurs in 80% of
adults with asymptomatic AS and has no known prognostic
significance.
Exercise testing should not be performed in symptomatic
patients owing to a high risk of complications. However, in
asymptomatic patients, exercise testing is relatively safe and
may provide information that is not uncovered during the
initial clinical evaluation.61,117,118,120 –124 When the medical
history is unclear, exercise testing can identify a limited
exercise capacity, abnormal blood pressure responses, or
even exercise-induced symptoms.117,118,124 In one series,117
patients manifesting symptoms, abnormal blood pressure
(less than 20-mm Hg increase), or ST-segment abnormalities
with exercise had a symptom-free survival at 2 years of only
19% compared with 85% symptom-free survival in those
with none of these findings with exercise. Four patients died
during the course of this study (1.2% annual mortality rate);
all had an aortic valve area less than 0.7 cm2 and an abnormal
exercise test. In another series,118 exercise testing brought out
symptoms in 29% of patients who were considered asymptomatic before testing; in these patients, spontaneous symptoms developed in 51% over the next year compared with
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only 11% of patients who had no symptoms on exercise
testing. An abnormal hemodynamic response (e.g., hypotension or failure to increase blood pressure with exercise) in a
patient with severe AS is considered a poor prognostic finding.117,125 Finally, in selected patients, the observations made
during exercise may provide a basis for advice about physical
activity. Exercise testing in asymptomatic patients should be
performed only under the supervision of an experienced physician with close monitoring of blood pressure and the ECG.
3.1.4.3. Serial Evaluations
The frequency of follow-up visits to the physician depends on
the severity of the valvular stenosis and on the presence of
comorbid conditions. Recognizing that an optimal schedule
for repeated medical examinations has not been defined,
many physicians perform an annual history and physical
examination on patients with asymptomatic AS of any degree. An essential component of each visit is patient education about the expected disease course and symptoms of AS.
Periodic echocardiography may be appropriate as discussed
below. Patients should be advised to promptly report the
development of any change in exercise tolerance, exertional
chest discomfort, dyspnea, lightheadedness, or syncope.
Serial echocardiography is an important part of an integrated approach that includes a detailed history, physical
examination, and, in some patients, a carefully monitored
exercise test. Because the rate of progression varies considerably, clinicians often perform an annual echocardiogram on
patients known to have moderate to severe AS. Serial
echocardiograms are helpful for assessing changes in stenosis
severity, LV hypertrophy, and LV function. Therefore, in
patients with severe AS, an echocardiogram every year may
be appropriate. In patients with moderate AS, serial studies
performed every 1 to 2 years are satisfactory, and in patients
with mild AS, serial studies can be performed every 3 to 5
years. Echocardiograms should be performed more frequently
if there is a change in signs or symptoms.
3.1.4.4. Medical Therapy (Updated)
Antibiotic prophylaxis against recurrent rheumatic fever is
indicated for patients with rheumatic AS. Patients with
associated systemic arterial hypertension should be treated
cautiously with appropriate antihypertensive agents. With
these exceptions, there is no specific medical therapy for
patients who have not yet developed symptoms. Patients who
develop symptoms require surgery, not medical therapy.
There are no medical treatments proven to prevent or delay
the disease process in the aortic valve leaflets. However, the
association of AS with clinical factors similar to those
associated with atherosclerosis and the mechanisms of disease at the tissue level50 – 60,99 –103,126 –129 have led to the
hypothesis that intervention may be possible to slow or
prevent disease progression in the valve leaflet.127,130 Specifically, the effect of lipid-lowering therapy on progression of
calcific AS has been examined in several small retrospective
studies using echocardiography or cardiac computed tomography to measure disease severity,131–136 suggesting a benefit
of statins. However, a prospective, randomized, placebocontrolled trial in patients with calcific aortic valve disease
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failed to demonstrate a benefit of atorvastatin in reducing the
progression of aortic valve stenosis over a 3-year period.137 It
is noteworthy that the patients in this study had high levels of
aortic valve calcification by computed tomography and evidence of moderate to severe AS at baseline, based on peak
aortic valve gradient (48 to 50 mm Hg), aortic valve area
(1.02 to 1.03 cm2), and peak jet velocity (3.39 to 3.45 m per
second). It is possible that the calcific process was too
advanced in these patients to be reversed by short-term statin
therapy. Thus, further trials in patients with less severe aortic
valve calcification, with longer follow-up periods, are needed.
In the meanwhile, evaluation and modification of cardiac risk
factors is important in patients with aortic valve disease to
prevent concurrent CAD.
3.1.4.5. Physical Activity and Exercise
Recommendations for physical activity are based on the
clinical examination, with special emphasis on the hemodynamic severity of the stenotic lesion. The severity can usually
be judged by Doppler echocardiography, but in borderline
cases, diagnostic cardiac catheterization may be necessary to
accurately define the degree of stenosis.
Recommendations on participation in competitive sports
have been published by the Task Force on Acquired Valvular
Heart Disease of the 36th Bethesda Conference.138 Physical
activity is not restricted in asymptomatic patients with mild
AS; these patients can participate in competitive sports.
Patients with moderate to severe AS should avoid competitive sports that involve high dynamic and static muscular
demands. Other forms of exercise can be performed safely,
but it is advisable to evaluate such patients with an exercise
test before they begin an exercise or athletic program.
3.1.5. Indications for Cardiac Catheterization
Class I
1. Coronary angiography is recommended before AVR in
patients with AS at risk for CAD (see Section 10.2).
(Level of Evidence: B)
2. Cardiac catheterization for hemodynamic measurements is recommended for assessment of severity of AS
in symptomatic patients when noninvasive tests are
inconclusive or when there is a discrepancy between
noninvasive tests and clinical findings regarding severity of AS. (Level of Evidence: C)
3. Coronary angiography is recommended before AVR in
patients with AS for whom a pulmonary autograft
(Ross procedure) is contemplated and if the origin of
the coronary arteries was not identified by noninvasive
technique. (Level of Evidence: C)
Class III
1. Cardiac catheterization for hemodynamic measurements is not recommended for the assessment of severity of AS before AVR when noninvasive tests are
adequate and concordant with clinical findings. (Level
of Evidence: C)
2. Cardiac catheterization for hemodynamic measurements is not recommended for the assessment of LV
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function and severity of AS in asymptomatic patients.
(Level of Evidence: C)
In patients with AS, the indications for cardiac catheterization
and angiography are essentially the same as in other conditions, namely, to assess the coronary circulation and confirm
or clarify the clinical diagnosis. In preparation for AVR,
coronary angiography is indicated in patients suspected of
having CAD, as discussed in Section 10.2. If the clinical and
echocardiographic data are typical of severe isolated AS,
coronary angiography may be all that is needed before AVR. A
complete left- and right-heart catheterization may be necessary
to assess the hemodynamic severity of the AS if there is a
discrepancy between clinical and echocardiographic data.
The pressure gradient across a stenotic valve is related to
the valve orifice area and the transvalvular flow.139 Thus, in
the presence of depressed cardiac output, relatively low pressure
gradients may be obtained in patients with severe AS. On the
other hand, during exercise or other high-flow states, significant
pressure gradients can be measured in minimally stenotic valves.
For these reasons, complete assessment of AS requires
• measurement of transvalvular flow
• determination of the mean transvalvular pressure gradient
• calculation of the effective valve area.
Attention to detail with accurate measurements of pressure
and flow is important, especially in patients with low cardiac
output or a low transvalvular pressure gradient.
3.1.6. Low-Flow/Low-Gradient Aortic Stenosis
Class IIa
1. Dobutamine stress echocardiography is reasonable to
evaluate patients with low-flow/low-gradient AS and
LV dysfunction. (Level of Evidence: B)
2. Cardiac catheterization for hemodynamic measurements with infusion of dobutamine can be useful for
evaluation of patients with low-flow/low-gradient AS
and LV dysfunction. (Level of Evidence: C)
Patients with severe AS and low cardiac output often present
with a relatively low transvalvular pressure gradient (i.e.,
mean gradient less than 30 mm Hg). Such patients can be
difficult to distinguish from those with low cardiac output and
only mild to moderate AS. In the former (true anatomically
severe AS), the stenotic lesion contributes to an elevated
afterload, decreased ejection fraction, and low stroke volume.
In the latter, primary contractile dysfunction is responsible for
the decreased ejection fraction and low stroke volume; the
problem is further complicated by reduced valve opening
forces that contribute to limited valve mobility and apparent
stenosis. In both situations, the low-flow state and lowpressure gradient contribute to a calculated effective valve
area that can meet criteria for severe AS. Alternate measures
of AS severity have been proposed as being less flow
dependent than gradients or valve area. These include valve
resistance and stroke work loss. However, all of these
measures are flow dependent, have not been shown to predict
clinical outcome, and have not gained widespread clinical
use.140
In selected patients with low-flow/low-gradient AS and LV
dysfunction, it may be useful to determine the transvalvular
pressure gradient and to calculate valve area during a baseline
state and again during exercise or low-dose pharmacological
(i.e., dobutamine infusion) stress, with the goal of determining whether stenosis is severe or only moderate in severity.123,141–147 Such studies can be performed in the echocardiography laboratory or in the cardiac catheterization
laboratory. This approach is based on the notion that patients
who do not have true anatomically severe stenosis will
exhibit an increase in the valve area and little change in
gradient during an increase in stroke volume.141,142 Thus, if a
dobutamine infusion produces an increment in stroke volume
and an increase in valve area greater than 0.2 cm2 and little
change in gradient, it is likely that baseline evaluation
overestimated the severity of stenosis. In contrast, patients with
severe AS will have a fixed valve area with an increase in stroke
volume and an increase in gradient. These patients are likely to
respond favorably to surgery. Patients who fail to show an
increase in stroke volume with dobutamine (less than 20%),
referred to as “lack of contractile reserve,” appear to have a very
poor prognosis with either medical or surgical therapy.2,148
Dobutamine stress testing in patients with AS should be performed only in centers with experience in pharmacological stress
testing and with a cardiologist in attendance.
The clinical approach to the patient with low-output AS
relies on integration of multiple sources of data. In
addition to measurement of Doppler velocity, gradient, and
valve area, the extent of valve calcification should be
assessed. Severe calcification suggests that AVR may be
beneficial. When transthoracic images are suboptimal,
transesophageal imaging or fluoroscopy may be used to
assess the degree of valve calcification and orifice area.
The risk of surgery and patient comorbidities also are taken into
account. Although patients with low-output severe AS have a
poor prognosis, in those with contractile reserve, outcome is still
better with AVR than with medical therapy.148 Some patients
without contractile reserve may also benefit from AVR, but
decisions in these high-risk patients must be individualized
because there are no data indicating who will have a better
outcome with surgery.
3.1.7. Indications for Aortic Valve Replacement
Class I
1. AVR is indicated for symptomatic patients with severe
AS.* (Level of Evidence: B)
2. AVR is indicated for patients with severe AS* undergoing coronary artery bypass graft surgery (CABG).
(Level of Evidence: C)
3. AVR is indicated for patients with severe AS* undergoing surgery on the aorta or other heart valves. (Level
of Evidence: C)
4. AVR is recommended for patients with severe AS* and
LV systolic dysfunction (ejection fraction less than
0.50). (Level of Evidence: C)
*See Table 4.27
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Figure 3. Management strategy for patients with severe aortic stenosis.
Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may
also be helpful when there is discordance between clinical findings and echocardiography. Modified from CM Otto. Valvular aortic stenosis: disease severity and timing of
intervention. J Am Coll Cardiol 2006;47:2141–51.149 AVA indicates aortic valve area; BP, blood pressure; CABG, coronary artery bypass graft surgery; echo, echocardiography; LV, left ventricular; and Vmax, maximal velocity across aortic valve by Doppler echocardiography.
Class IIa
1. AVR is reasonable for patients with moderate AS*
undergoing CABG or surgery on the aorta or other
heart valves (see Section 3.7 on combined multiple
valve disease and Section 10.4 on AVR in patients
undergoing CABG). (Level of Evidence: B)
Class IIb
1. AVR may be considered for asymptomatic patients
with severe AS* and abnormal response to exercise
(e.g., development of symptoms or asymptomatic hypotension). (Level of Evidence: C)
2. AVR may be considered for adults with severe asymptomatic AS* if there is a high likelihood of rapid progression (age, calcification, and CAD) or if surgery might be
delayed at the time of symptom onset. (Level of Evidence: C)
3. AVR may be considered in patients undergoing CABG
who have mild AS* when there is evidence, such as
moderate to severe valve calcification, that progression
may be rapid. (Level of Evidence: C)
4. AVR may be considered for asymptomatic patients
with extremely severe AS (aortic valve area less than 0.6
cm2, mean gradient greater than 60 mm Hg, and jet velocity
greater than 5.0 m per second) when the patient’s expected
operative mortality is 1.0% or less. (Level of Evidence: C)
Class III
1. AVR is not useful for the prevention of sudden death in
asymptomatic patients with AS who have none of the
findings listed under the Class IIa/IIb recommendations. (Level of Evidence: B)
In adults with severe, symptomatic, calcific AS, AVR is the
only effective treatment. Younger patients with congenital or
rheumatic AS may be candidates for valvotomy (see Section
6.1 under management of adolescents and young adults).
Although there is some lack of agreement about the optimal
timing of surgery in asymptomatic patients, it is possible to
develop rational guidelines for most patients. A proposed
management strategy for patients with severe AS is shown in
Fig. 3.149 Particular consideration should be given to the
natural history of asymptomatic patients and to operative
risks and outcomes after surgery. See also Section 7.2.
3.1.7.1. Symptomatic Patients
In symptomatic patients with AS, AVR improves symptoms and
improves survival.106,150 –155 These salutary results of surgery are
partly dependent on LV function. The outcome is similar in
patients with normal LV function and in those with moderate
depression of contractile function. The depressed ejection fraction in many patients in this latter group is caused by excessive
afterload (afterload mismatch),66 and LV function improves after
AVR in such patients. If LV dysfunction is not caused by
afterload mismatch, survival is still improved, but improvement
in LV function and resolution of symptoms might not be
complete after AVR.150,154,156 –158 Therefore, in the absence of
serious comorbid conditions, AVR is indicated in virtually all
symptomatic patients with severe AS. Because of the risk of
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sudden death, AVR should be performed promptly after the
onset of symptoms. Age is not a contraindication to surgery,
with several series showing outcomes similar to age-matched
normal subjects in the very elderly. The operative risks can be
estimated with readily available and well-validated online risk
calculators from the Society of Thoracic Surgeons (www.
sts.org) and the European System for Cardiac Operative Risk
Evaluation (www.euroscore.org),159 –161 as well as the risk calculator developed specifically for valvular heart surgery by
Ambler et al.162
3.1.7.2. Asymptomatic Patients
Many clinicians are reluctant to proceed with AVR in an
asymptomatic patient,163 whereas others are concerned about
caring for a patient with severe AS without surgery. Although
AVR is associated with low perioperative morbidity and
mortality in many centers, the average perioperative mortality
in the STS database is 3.0% to 4.0% for isolated AVR and
5.5% to 6.8% for AVR plus CABG.164,165 These rates are
33% higher in centers with low volume than in centers with
the highest surgical volume.166 A review of Medicare data,167
involving 684 US hospitals and more than 142 000 patients,
indicates that the average in-hospital mortality for AVR in
patients over the age of 65 years is 8.8% (13.0% in lowvolume centers and 6.0% in high-volume centers). In addition, despite improved longevity of current-generation bioprosthetic valves,168,169 AVR in young patients subjects them
to the risks of structural valve deterioration of bioprostheses168,170 –174 and the appreciable morbidity and mortality of
mechanical valves.172,174 –178 Thus, the combined risk of
surgery in older patients and the late complications of a
prosthesis in younger patients needs to be balanced against
the possibility of preventing sudden death, which, as noted
above, occurs at a rate of less than 1.0% per year.
Despite these considerations, some difference of opinion
persists among clinicians regarding the indications for AVR
in asymptomatic patients with severe AS, because the probability of remaining free of cardiac symptoms without surgery is less than 50% at 5 years.61,96,116 Some argue that
irreversible myocardial depression or fibrosis might develop
during a prolonged asymptomatic stage and that this might
preclude an optimal outcome. Such irreversibility has not
been proved, but this concept has been used to support early
surgery.152,179 Still others attempt to identify patients who are
at especially high risk of sudden death without surgery,
although data supporting this approach are limited. Currently,
there is general agreement that the risk of AVR exceeds any
potential benefit in patients with severe AS who are truly
asymptomatic with normal LV systolic function. However, as
improved valve substitutes are developed and methods of
valve replacement become safer, the risk-benefit balance may
change to favor earlier intervention in AS.
Studies suggest that patients at risk of rapid disease
progression and impending symptom onset can be identified
on the basis of clinical and echocardiographic parameters.
The rate of hemodynamic progression is faster in patients
with asymptomatic severe96 or mild to moderate98 AS when
patient age is over 50 years and severe valve calcification or
concurrent CAD is present. Adverse clinical outcomes are
more likely in patients with a more rapid rate of hemodynamic progression, defined as an annual increase in aortic jet
velocity greater than 0.3 m per second per year or a decrease
in valve area greater than 0.1 cm2 per year.61,96 The presence
of left ventricular hypertrophy by ECG and smaller aortic
valve area by Doppler echocardiography predict the development of symptoms.61,116 In addition, serum levels of B-type
natriuretic peptide may provide important prognostic information.180 In situations in which there is delay between
symptom onset and surgical intervention, patients are at high
risk of adverse outcomes during the waiting period. These
higher-risk patients might warrant more frequent echocardiography or earlier consideration of valve replacement.
In the 1998 ACC/AHA Guidelines for the Management of
Patients with Valvular Heart Disease, consideration was
given to performing AVR in patients with AS and severe LV
hypertrophy and those with ventricular tachycardia (Class
IIb). The current committee determined that there was insufficient evidence to support those recommendations, which are
not carried forward in the current document.
3.1.7.3. Patients Undergoing Coronary Artery Bypass or
Other Cardiac Surgery
Patients with severe AS, with or without symptoms, who are
undergoing CABG should undergo AVR at the time of the
revascularization procedure. Similarly, patients with severe
AS undergoing surgery on other valves (such as MV repair)
or the aortic root should also undergo AVR as part of the
surgical procedure. In patients with moderate AS, it is
generally accepted practice to perform AVR at the time of
CABG.181–185 Many clinicians also recommend AVR for
moderate AS at the time of MV or aortic root surgery (for
further detail, see Section 3.7, “Multiple Valve Disease”).
However, there are no data to support a policy of AVR for
mild AS at the time of CABG, with the exception of those
patients with moderate to severe valvular calcification.98,181,182,185–187 Recommendations for AVR at the time of
CABG are discussed in Section 10.4.
3.1.8. Aortic Balloon Valvotomy
Class IIb
1. Aortic balloon valvotomy might be reasonable as a
bridge to surgery in hemodynamically unstable adult
patients with AS who are at high risk for AVR. (Level
of Evidence: C)
2. Aortic balloon valvotomy might be reasonable for
palliation in adult patients with AS in whom AVR
cannot be performed because of serious comorbid
conditions. (Level of Evidence: C)
Class III
1. Aortic balloon valvotomy is not recommended as an
alternative to AVR in adult patients with AS; certain
younger adults without valve calcification may be an
exception (see Section 6.1.3). (Level of Evidence: B)
Percutaneous balloon aortic valvotomy is a procedure in
which 1 or more balloons are placed across a stenotic valve
and inflated to decrease the severity of AS.188 –190 This
procedure has an important role in treating adolescents and
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young adults with AS (see Section 6.1.) but a very limited
role in older adults. The mechanism underlying relief of the
stenotic lesion in older adults is fracture of calcific deposits
within the valve leaflets and, to a minor degree, stretching of
the annulus and separation of the calcified or fused commissures.191–193 Immediate hemodynamic results include a moderate reduction in the transvalvular pressure gradient, but the
postvalvotomy valve area rarely exceeds 1.0 cm2. Despite the
modest change in valve area, an early symptomatic improvement is usually seen. However, serious acute complications
occur with a frequency greater than 10%,194 –200 and restenosis and clinical deterioration occur within 6 to 12 months in
most patients.195,200 –204 Therefore, in adults with AS, balloon
valvotomy is not a substitute for AVR.204 –207
Some clinicians contend that despite the procedural morbidity and mortality and limited long-term results, balloon
valvotomy can have a temporary role in the management of
some symptomatic patients who are not initially candidates
for AVR.207 For example, patients with severe AS and
refractory pulmonary edema or cardiogenic shock might
benefit from aortic valvuloplasty as a “bridge” to surgery; an
improved hemodynamic state may reduce the risks of surgery. However, most clinicians recommend proceeding directly to AVR in these cases. The indications for palliative
valvotomy in patients in whom AVR cannot be recommended
because of serious comorbid conditions are even less well
established, with no data to suggest improved longevity,
although some patients do report a decrease in symptoms.
Most asymptomatic patients with severe AS who require
urgent noncardiac surgery can undergo surgery at a reasonably low risk with monitoring of anesthesia and attention to
fluid balance.208 –212 Balloon aortic valvotomy is not recommended for these patients. If preoperative correction of AS is
needed, they should be considered for AVR.
3.1.9. Medical Therapy for the Inoperable Patient
Comorbid conditions (e.g., malignancy) or, on occasion,
patient preferences might preclude AVR for severe AS.
Under such circumstances, there is no therapy that prolongs
life, and only limited medical therapies are available to
alleviate symptoms. Patients with evidence of pulmonary
congestion can benefit from cautious treatment with digitalis,
diuretics, and angiotensin converting enzyme (ACE) inhibitors. Indeed, a cautious reduction in central blood volume and
LV preload can be efficacious in some patients with heart
failure symptoms. It should be recognized, however, that
excessive preload reduction can depress cardiac output and
reduce systemic arterial pressure; patients with severe AS are
especially subject to this untoward effect due to a small
hypertrophied ventricle. In patients with acute pulmonary
edema due to AS, nitroprusside infusion may be used to
reduce congestion and improve LV performance. Such therapy should be performed in an intensive care unit under the
guidance of invasive hemodynamic monitoring.213 Digitalis
should be reserved for patients with depressed systolic
function or atrial fibrillation. Atrial fibrillation and other atrial
arrhythmias have an adverse effect on atrial pump function
and ventricular rate; if prompt cardioversion is unsuccessful,
pharmacological control of the ventricular rate is essential. If
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angina is the predominant symptom, cautious use of nitrates
and beta blockers can provide relief. There is no specific
medical therapy for syncope unless it is caused by a bradyarrhythmia or tachyarrhythmia.
3.1.10. Evaluation After Aortic Valve Replacement
Considering the known complications of prosthetic aortic
valves,168,170 –178,214 patients require periodic clinical and selected laboratory examinations after AVR. A complete history and physical examination should be performed at least
once a year. Indications for echocardiography are discussed
in Section 9.3.
3.1.11. Special Considerations in the Elderly
Because there is no effective medical therapy and balloon
valvotomy is not an acceptable alternative to surgery, AVR
must be considered in all elderly patients who have symptoms
caused by AS. Valve replacement is technically possible at
any age,215 but the decision to proceed with such surgery
depends on many factors, including the patient’s wishes and
expectations. Older patients with symptoms due to severe AS,
normal coronary arteries, and preserved LV function can
expect a better outcome than those with CAD or LV dysfunction.110 Certainly advanced cancer and permanent neurological defects as a result of stroke or dementia make cardiac
surgery inappropriate. Deconditioned and debilitated patients
often do not return to an active existence, and the presence of
the other comorbid disorders could have a major impact on
outcome.
In addition to the confounding effects of CAD and the
potential for stroke, other considerations are peculiar to older
patients. For example, a narrow LV outflow tract and a small
aortic annulus sometimes present in elderly women could
require enlargement of the annulus. Heavy calcification of the
valve, annulus, and aortic root may require debridement.
Occasionally, a composite valve-aortic graft is needed. Likewise, excessive or inappropriate hypertrophy associated with
valvular stenosis can be a marker for perioperative morbidity
and mortality.81,83 Preoperative recognition of elderly patients
with marked LV hypertrophy followed by appropriate perioperative management can reduce this morbidity and mortality substantially. There is no perfect method for weighing all
of the relevant factors and identifying specifically high- and
low-risk elderly patients, but this risk can be estimated well in
individual patients.159 –162,216 The decision to proceed with
AVR depends on an imprecise analysis that considers the
balance between the potential for improved symptoms and
survival and the morbidity and mortality of surgery.217–219
3.2. Aortic Regurgitation
3.2.1. Etiology
There are a number of common causes of AR. These include
idiopathic dilatation of the aorta, congenital abnormalities of
the aortic valve (most notably bicuspid valves), calcific
degeneration, rheumatic disease, infective endocarditis, systemic hypertension, myxomatous degeneration, dissection of
the ascending aorta, and Marfan syndrome. Less common
causes include traumatic injuries to the aortic valve, ankylosing spondylitis, syphilitic aortitis, rheumatoid arthritis, osteo-
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genesis imperfecta, giant cell aortitis, Ehlers-Danlos syndrome, Reiter’s syndrome, discrete subaortic stenosis, and
ventricular septal defects with prolapse of an aortic cusp.
Recently, anorectic drugs have also been reported to cause
AR (see Section 3.9.). The majority of these lesions produce
chronic AR with slow, insidious LV dilation and a prolonged
asymptomatic phase (Table 4).27 Other lesions, in particular
infective endocarditis, aortic dissection, and trauma, more
often produce acute severe AR, which can result in sudden
catastrophic elevation of LV filling pressures and reduction in
cardiac output.
3.2.2. Acute Aortic Regurgitation
3.2.2.1. Pathophysiology
In acute severe AR, the sudden large regurgitant volume is
imposed on a left ventricle of normal size that has not had
time to accommodate the volume overload. With an abrupt
increase in end-diastolic volume, the ventricle operates on the
steep portion of a normal diastolic pressure-volume relationship, and LV end-diastolic and left atrial pressures may
increase rapidly and dramatically. The Frank-Starling mechanism is used, but the inability of the ventricle to develop
compensatory chamber dilatation acutely results in a decrease
in forward stroke volume. Although tachycardia develops as
a compensatory mechanism to maintain cardiac output, this is
often insufficient. Hence, patients frequently present with
pulmonary edema or cardiogenic shock. Acute AR creates
especially marked hemodynamic changes in patients with
pre-existing pressure overload hypertrophy, in whom the
small, noncompliant LV cavity is set on an even steeper
diastolic pressure-volume relationship and has reduced preload reserve. Examples of this latter situation include aortic
dissection in patients with systemic hypertension, infective
endocarditis in patients with pre-existing AS, and acute
regurgitation after balloon valvotomy or surgical commissurotomy for congenital AS. Patients may also present with signs
and symptoms of myocardial ischemia. As the LV enddiastolic pressure approaches the diastolic aortic and coronary artery pressures, myocardial perfusion pressure in the
subendocardium is diminished. LV dilation and thinning of
the LV wall result in increased afterload, and this combines
with tachycardia to increase myocardial oxygen demand.
Therefore, ischemia and its consequences, including sudden
death, occur commonly in acute severe AR.
3.2.2.2. Diagnosis
Many of the characteristic physical findings of chronic AR
are modified or absent when valvular regurgitation is acute,
which can lead to underestimation of its severity. LV size
may be normal on physical examination, and cardiomegaly
may be absent on chest X-ray. Pulse pressure may not be
increased because systolic pressure is reduced and the aortic
diastolic pressure equilibrates with the elevated LV diastolic
pressure. Because this diastolic pressure equilibration between aorta and ventricle can occur before the end of diastole,
the diastolic murmur may be short and/or soft and therefore
poorly heard. The elevated LV diastolic pressure can close
the MV prematurely, reducing the intensity of the first heart
sound. An apical diastolic rumble can be present, but it is
usually brief and without presystolic accentuation. Tachycardia is invariably present.
Echocardiography is indispensable in confirming the presence and severity of the valvular regurgitation, determining
its cause, estimating the degree of pulmonary hypertension (if
TR is present), and determining whether there is rapid
equilibration of aortic and LV diastolic pressure. Evidence for
rapid pressure equilibration includes a short AR diastolic
half-time (less than 300 ms), a short mitral deceleration time
(less than 150 ms), or premature closure of the MV.
Acute AR caused by aortic root dissection is a surgical
emergency that requires particularly prompt identification
and management. Transesophageal echocardiography is indicated when aortic dissection is suspected.220 –222 In some
settings, computed tomographic imaging or magnetic resonance imaging should be performed if this will lead to a more
rapid diagnosis than can be achieved by transesophageal
echocardiography.220,221,223 Cardiac catheterization, aortography, and coronary angiography are rarely required, are
associated with increased risk, and might delay urgent surgery unnecessarily.221,224 –227 Angiography should be considered only when the diagnosis cannot be determined by
noninvasive imaging and when patients have known CAD,
especially those with previous CABG (see Section 10.2).
3.2.2.3. Treatment
Death due to pulmonary edema, ventricular arrhythmias,
electromechanical dissociation, or circulatory collapse is
common in acute severe AR, even with intensive medical
management. Urgent surgical intervention is recommended.
Nitroprusside, and possibly inotropic agents such as dopamine or dobutamine to augment forward flow and reduce LV
end-diastolic pressure, may be helpful to manage the patient
temporarily before surgery. Intra-aortic balloon counterpulsation is contraindicated. Although beta blockers are often
used in treating aortic dissection, these agents should be used
very cautiously, if at all, in the setting of acute AR because
they will block the compensatory tachycardia. In patients
with acute severe AR resulting from infective endocarditis,
surgery should not be delayed, especially if there is hypotension, pulmonary edema, or evidence of low output. In patients
with mild acute AR, antibiotic treatment may be all that is
necessary if the patient is hemodynamically stable. Exceptions to this latter recommendation are discussed in Section
4.6.1.
3.2.3. Chronic Aortic Regurgitation
3.2.3.1. Pathophysiology
The left ventricle responds to the volume load of chronic AR
with a series of compensatory mechanisms, including an
increase in end-diastolic volume, an increase in chamber
compliance that accommodates the increased volume without
an increase in filling pressures, and a combination of eccentric and concentric hypertrophy. The greater diastolic volume
permits the ventricle to eject a large total stroke volume to
maintain forward stroke volume in the normal range. This is
accomplished through rearrangement of myocardial fibers
with the addition of new sarcomeres and development of
eccentric LV hypertrophy.228 As a result, preload at the
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sarcomere level remains normal or near normal, and the
ventricle retains its preload reserve. The enhanced total stroke
volume is achieved through normal performance of each
contractile unit along the enlarged circumference.229 Thus,
LV ejection performance is normal, and ejection phase
indexes such as ejection fraction and fractional shortening
remain in the normal range. However, the enlarged chamber
size, with the associated increase in systolic wall stress, also
results in an increase in LV afterload and is a stimulus for
further hypertrophy.228,230 Thus, AR represents a condition of
combined volume overload and pressure overload.231 As the
disease progresses, recruitment of preload reserve and compensatory hypertrophy permit the ventricle to maintain normal ejection performance despite the elevated afterload.232,233
The majority of patients remain asymptomatic throughout
this compensated phase, which may last for decades. Vasodilator therapy has the potential to reduce the hemodynamic
burden in such patients.
For purposes of the subsequent discussion, patients with
normal LV systolic function will be defined as those with
normal LV ejection fraction at rest. It is recognized that other
indices of LV function may not be “normal” in chronic severe
AR and that the hemodynamic abnormalities noted above
may be considerable. It is also recognized that the transition
to LV systolic dysfunction represents a continuum and that
there is no single hemodynamic measurement that represents
the absolute boundary between normal LV systolic function
and LV systolic dysfunction.
In a large subset of patients, the balance between afterload
excess, preload reserve, and hypertrophy cannot be maintained indefinitely. Preload reserve may be exhausted,233
and/or the hypertrophic response may be inadequate,63 so that
further increases in afterload result in a reduction in ejection
fraction, first into the low normal range and then below
normal. Impaired myocardial contractility may also contribute to this process. Patients often develop dyspnea at this
point in the natural history. In addition, diminished coronary
flow reserve in the hypertrophied myocardium may result in
exertional angina.234 However, this transition may be much
more insidious, and it is possible for patients to remain
asymptomatic until severe LV dysfunction has developed.
LV systolic dysfunction (defined as an ejection fraction below
normal at rest) is initially a reversible phenomenon related
predominantly to afterload excess, and full recovery of LV size
and function is possible with AVR.235–246 With time, during
which the ventricle develops progressive chamber enlargement
and a more spherical geometry, depressed myocardial contractility predominates over excessive loading as the cause of
progressive systolic dysfunction. This can progress to the extent
that the full benefit of surgical correction of the regurgitant
lesion, in terms of recovery of LV function and improved
survival, can no longer be achieved.244,247–256
A large number of studies have identified LV systolic function and end-systolic size as the most important determinants of
survival and postoperative LV function in patients undergoing
AVR for chronic AR.235,237–267 Studies of predictors of surgical
outcome are listed in Table 13.
Among patients undergoing valve replacement for chronic
AR with preoperative LV systolic dysfunction (defined as an
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ejection fraction below normal at rest), several factors are
associated with worse functional and survival results after
operation. These are listed in Table 14.
3.2.3.2. Natural History
3.2.3.2.1. Asymptomatic Patients With Normal Left Ventricular Function. There are no truly large-scale studies evaluating
the natural history of asymptomatic patients in whom LV
systolic function was known to be normal (as determined by
invasive or noninvasive testing). The current recommendations
are derived from 9 published series268 –277 involving a total of
593 such patients (range, 27 to 104 patients/series) with a mean
follow-up period of 6.6 years (Table 15). This analysis is subject
to the usual limitations of comparisons of different clinical series
with different patient selection factors and different end points.
For example, 1 series270 represents patients receiving placebo in
a randomized drug trial278 that included some patients with
“early” New York Heart Association (NYHA) functional class II
symptoms (although none had “limiting” symptoms), and another272 represents patients receiving digoxin in a long-term
study comparing the effects of nifedipine with digoxin. In 2
studies,274,276 LV function was not reported in all patients, and it
is unclear whether all had normal LV systolic function at
baseline. In another study,275 20% of patients were not
asymptomatic but had “early” NYHA functional class II
symptoms, and the presence of these symptoms was a
significant predictor of death, LV dysfunction, or development of more severe symptoms. Some patients in this latter
series had evidence of LV systolic dysfunction (fractional
shortening as low as 18%).
The results of these 9 studies are summarized in Tables 15 and
16. The rate of progression to symptoms and/or LV systolic
dysfunction averaged 4.3% per year. Sudden death occurred in 7
of the 593 patients, for an average mortality rate of less than
0.2% per year. Seven of the 9 studies reported the rate of
development of asymptomatic LV dysfunction, defined as an
ejection fraction at rest below normal269 –273,275,276; 37 of a total
of 535 patients developed depressed systolic function at rest
without symptoms during a mean 5.9-year follow-up period, a
rate of 1.2% per year.
Despite the low likelihood of patients developing asymptomatic LV dysfunction, it should also be emphasized that more than
one fourth of patients who die or develop systolic dysfunction do
so before the onset of warning symptoms.269 –271,275 Thus, thorough questioning of patients regarding symptomatic status is not
sufficient in the serial evaluation of asymptomatic patients;
quantitative evaluation of LV function is also indispensable.
Moreover, patients at risk of future symptoms, death, or LV
dysfunction can also be identified on the basis of noninvasive
testing. Five of the natural history studies provide concordant
information on the variables associated with higher risk.270–272,275,276
These variables are age, LV end-systolic dimension (or volume),
LV end-diastolic dimension (or volume), and the LV ejection
fraction during exercise. In 1 study,275 the LV ejection fraction
during exercise was an independent risk factor. However, the
direction and magnitude of change in ejection fraction from rest
to exercise is related not only to myocardial contractility279 but
also to severity of volume overload271,278 –280 and exerciseinduced changes in preload and peripheral resistance.280 In 2
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Table 13.
October 7, 2008
Preoperative Predictors of Surgical Outcome in Aortic Regurgitation
Study
Design
No. of
Patients
Forman et al., 1980251
Retrospective
90
Survival
High-risk group identified by preoperative angiographic LV EF
less than 0.50
Henry et al., 1980257
Prospective
50
Survival
High-risk group identified by preoperative echocardiographic LV
FS less than 0.25 and/or ESD greater than 55 mm
Cunha et al., 1980250
Retrospective
86
Survival
High-risk group identified by preoperative echocardiographic LV
FS less than 0.30. Mortality also significantly associated with
preoperative ESD. Among patients with FS less than 0.30,
mortality higher in NYHA FC III-IV than in FC I-II.
Greves et al., 1981252
Retrospective
45
Survival
High-risk group identified by preoperative angiographic LV EF
less than 0.45 and/or CI less than 2.5 L/mm. Among patients
with EF less than 0.45, mortality higher in NYHA FC III-IV than
in FC I–II.
Kumpuris et al., 1982258
Prospective
43
Survival, heart failure,
LV function
Persistent LV dilatation after AVR predicted by preoperative
echocardiographic LV ESD, radius/thickness mean and endsystolic wall stress. All deaths occurred in patients with
persistent LV dilatation.
Gaasch et al., 1983253
Prospective
32
Symptoms, LV
function
Persistent LV dilatation after AVR predicted by echocardiographic
LV ESD greater than 2.6 cm/m2 and radius/thickness ratio
greater than 3.8. Trend toward worse survival in patients with
persistent LV dilatation.
Fioretti et al., 1983259
Retrospective
47
LV function
Persistent LV dysfunction predicted by preoperative EDD 75 mm
or greater and/or ESD 55 mm or greater
Stone et al., 1984260
Prospective
113
LV function
Normal LV function after AVR predicted by preoperative LV FS
greater than 0.26, ESD less than 55 mm, and EDD less than
80 mm. No preoperative variable predicted postoperative LV
function.
Bonow et al., 1985,
1988254, 245
Prospective
80
Survival, LV function
Postoperative survival and LV function predicted by preoperative
LV EF, FS, and ESD. High-risk group identified by subnormal
EF at rest. Among patients with subnormal EF, poor exercise
tolerance and prolonged duration of LV dysfunction identified
the highest-risk group.
Daniel et al., 1985261
Retrospective
84
Survival, symptoms,
LV function
Outcome after AVR predicted by preoperative LV FS and ESD.
Survival at 2.5 years was 90.5% with FS greater than 0.25
and ESD 55 mm or less but only 70% with ESD greater than
55 mm and FS 25% or less.
Cormier et al., 1986262
Prospective
73
Survival
High-risk group identified by preoperative LV EF less than 0.40
and ESD 55 mm or greater
Sheiban et al., 1986263
Retrospective
84
Survival
High-risk group identified by preoperative LV EF less than 0.50
and ESD greater than 55 mm
Carabello et al., 1987243
Retrospective
14
LV function
Postoperative LV EF predicted by preoperative ESD, FS, EDD, and
radius/thickness ratio
Taniguchi et al., 1987244
Retrospective
62
Survival
High-risk group identified by preoperative ESV greater than 200
ml/m2 and/or EF less than 0.40
Michel et al., 1995256
Retrospective
286
LV function
Postoperative LV dysfunction predicted by preoperative LV EF, FS,
ESD, and EDD
Klodas et al., 1996,
1997264, 265
Retrospective
289
Survival
High-risk group identified by symptom severity and preoperative
EF less than 0.50
Turina et al., 1998266
Retrospective
192
Survival
High-risk group identified by symptom severity, low EF, and
elevated end-diastolic volume
Study, Year
Outcome Assessed
Findings
AVR indicates aortic valve replacement; CI, cardiac index; EDD, end-diastolic dimension; EF, ejection fraction; ESD, end-systolic dimension; ESV, end-systolic
volume; FC, functional class; FS, fractional shortening; LV, left ventricular; and NYHA, New York Heart Association.
multivariate analyses,271,276 only age and end-systolic dimension
on initial study were independent predictors of outcome, as were
the rate of increase in end-systolic dimension and decrease in
resting ejection fraction during serial longitudinal studies.271
During a mean follow-up period of 8 years, patients with initial
end-systolic dimensions greater than 50 mm had a likelihood of
death, symptoms, and/or LV dysfunction of 19% per year. In
those with end-systolic dimensions of 40 to 50 mm, the likelihood was 6% per year, and when the dimension was less than 40
mm, it was zero.271
3.2.3.2.2. Asymptomatic Patients With Depressed Systolic
Function. The limited data in asymptomatic patients with
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Table 14. Factors Predictive of Reduced Postoperative
Survival and Recovery of Left Ventricular Function in Patients
With Aortic Regurgitation and Preoperative Left Ventricular
Systolic Dysfunction
Severity of preoperative symptoms or reduced exercise tolerance
Severity of depression of left ventricular ejection fraction
Duration of preoperative left ventricular systolic dysfunction
depressed LV ejection fraction indicate that the majority develop
symptoms that warrant AVR within 2 to 3 years.281–283 The
average rate of symptom onset in such patients is greater than
25% per year (Table 16).268 –277,281–288
Table 15.
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3.2.3.2.3. Symptomatic Patients. There are no contemporary
large-scale studies of the natural history of symptomatic
patients with chronic AR, because the onset of angina or
significant dyspnea is usually an indication for valve replacement. The data developed in the presurgical era indicate that
patients with dyspnea, angina, or overt heart failure have a
poor outcome with medical therapy, analogous to that of
patients with symptomatic AS. Mortality rates of greater than
10% per year have been reported in patients with angina
pectoris and greater than 20% per year in those with heart
failure.284 –286 LV function was not measured in these patients,
so it is unclear whether symptomatic patients with normal
Studies of the Natural History of Asymptomatic Patients With Aortic Regurgitation
No. of
Patients
Mean
Follow-Up,
y
Progression
to Symptoms,
Death, or LV
Dysfunction,
Rate per y
(%)
104
8.0
3.8
4
0.5
2
Outcome predicted by LV ESD,
EDD, change in EF with exercise,
and rate of change in ESD and
EF at rest with time.
30
4.7
2.1
3
2.1
0
3 Patients who developed
asymptomatic LV dysfunction
initially had lower PAP/ESV ratios
and trended toward higher LV
ESD and EDD and lower FS
Siemienczuk et al., 1989270
50
3.7
4.0
1
0.5
0
Patients included those receiving
placebo and medical dropouts in
a randomized drug trial; included
some patients with NYHA FC II
symptoms; outcome predicted by
LV ESV, EDV, change in EF with
exercise, and end-systolic wall
stress
Scognamiglio et al., 1994*272
74
6.0
5.7
15
3.4
0
All patients received digoxin as part
of a randomized trial
101
4.6
3.0
6
1.3
0
Outcome predicted by pulse
pressure, LV ESD, EDD, and EF
at rest
Ishii et al., 1996274
27
14.2
3.6
—
0
Development of symptoms
predicted by systolic BP, LV ESD,
EDD, mass index, and wall
thickness. LV function not
reported in all patients
Borer et al., 1998275
104
7.3
6.2
7
0.9
4
20% of patients in NYHA FC II;
outcome predicted by initial FC II
symptoms, change in LV EF with
exercise, LV ESD, and LV FS
0.1
0
Development of symptoms
predicted by LV ESD and EDD.
LV function not reported in all
patients
1
Placebo control group in 7-year
vasodilator clinical trial
Study, Year
Bonow et al., 1983,
1991268, 271
Scognamiglio et al., 1986*
Tornos et al., 1995273
269
Progression to
Asymptomatic
LV Dysfunction
n
Rate per y
(%)
Mortality, No.
of Patients
Tarasoutchi et al., 2003276
72
10
4.7
1
Evangelista et al., 2005277
31
7
3.6
—
6.6
4.3
37
Average
593
—
—
1.2
Comments
0.18% per y
A dash indicates that data were not available. *Two studies by the same authors involved separate patient groups.
BP indicates blood pressure; EDD, end-diastolic dimension; EDV, end-diastolic volume; EF, ejection fraction; ESD, end-systolic dimension; ESV, end-systolic volume;
FC, functional class; FS, fractional shortening; LV, left ventricular; NYHA, New York Heart Association; and PAP, pulmonary artery pressure.
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Table 16.
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Natural History of Aortic Regurgitation
Asymptomatic patients with normal LV systolic
function268–277
Progression to symptoms and/or LV
dysfunction
Less than 6% per y
Progression to asymptomatic LV dysfunction
Less than 3.5% per y
Sudden death
Less than 0.2% per y
Asymptomatic patients with LV
dysfunction281–283
Progression to cardiac symptoms
Greater than 25% per y
Symptomatic patients284–288
Mortality rate
Greater than 10% per y
LV indicates left ventricular.
ejection fractions have the same adverse outcome as symptomatic patients with LV dysfunction; however, subsequent
data indicate a poor outcome for symptomatic patients with
medical therapy, even among those with preserved LV
systolic function.274,287,288
3.2.3.3. Diagnosis and Initial Evaluation
Class I
1. Echocardiography is indicated to confirm the presence and severity of acute or chronic AR. (Level of
Evidence: B)
2. Echocardiography is indicated for diagnosis and assessment of the cause of chronic AR (including valve
morphology and aortic root size and morphology) and
for assessment of LV hypertrophy, dimension (or
volume), and systolic function. (Level of Evidence: B)
3. Echocardiography is indicated in patients with an
enlarged aortic root to assess regurgitation and the
severity of aortic dilatation. (Level of Evidence: B)
4. Echocardiography is indicated for the periodic reevaluation of LV size and function in asymptomatic
patients with severe AR. (Level of Evidence: B)
5. Radionuclide angiography or magnetic resonance imaging is indicated for the initial and serial assessment
of LV volume and function at rest in patients with AR
and suboptimal echocardiograms. (Level of Evidence:
B)
6. Echocardiography is indicated to re-evaluate mild,
moderate, or severe AR in patients with new or
changing symptoms. (Level of Evidence: B)
Class IIa
1. Exercise stress testing for chronic AR is reasonable for
assessment of functional capacity and symptomatic
response in patients with a history of equivocal symptoms. (Level of Evidence: B)
2. Exercise stress testing for patients with chronic AR is
reasonable for the evaluation of symptoms and functional capacity before participation in athletic activities. (Level of Evidence: C)
3. Magnetic resonance imaging is reasonable for the
estimation of AR severity in patients with unsatisfactory echocardiograms. (Level of Evidence: B)
Class IIb
1. Exercise stress testing in patients with radionuclide
angiography may be considered for assessment of LV
function in asymptomatic or symptomatic patients
with chronic AR. (Level of Evidence: B)
The diagnosis of chronic severe AR can usually be made on
the basis of the diastolic murmur, displaced LV impulse, wide
pulse pressure, and characteristic peripheral findings that
reflect wide pulse pressure. A third heart sound is often heard
as a manifestation of the volume load and is not necessarily
an indication of heart failure. An Austin-Flint rumble is a
specific finding for severe AR.289,290 In many patients with
more mild to moderate AR, the physical examination will
identify the regurgitant lesion but will be less accurate in
determining its severity. When the diastolic murmur of AR is
louder in the third and fourth right intercostal spaces than in
the third and fourth left intercostal spaces, the AR likely
results from aortic root dilatation rather than from a deformity
of the leaflets alone.291 The chest X-ray and ECG are helpful
in evaluating overall heart size and rhythm, evidence of LV
hypertrophy, and evidence of conduction disorders.
Echocardiography is indicated:
• to confirm the diagnosis of AR if there is an equivocal
diagnosis based on physical examination
• to assess the cause of AR and to assess valve morphology
• to provide a semiquantitative estimate of the severity of
AR
• to assess LV dimension, mass, and systolic function
• to assess aortic root size.
In asymptomatic patients with preserved systolic function,
these initial measurements represent the baseline information
with which future serial measurements can be compared. In
addition to semiquantitative assessment of the severity of AR
by color flow jet area and width by Doppler echocardiography, quantitative measurement of regurgitant volume, regurgitant fraction, and regurgitant orifice area can be performed
in experienced laboratories (Table 4).27 Indirect measures of
severity of AR are helpful, using the rate of decline in
regurgitant gradient measured by the slope of diastolic flow
velocity, the degree of reversal in pulse wave velocity in the
descending aorta, and the magnitude of LV outflow tract
velocity.2,292,293 Comparison of stroke volumes at the aortic
valve compared with another uninvolved valve may provide
a quantitative measurement of regurgitant fraction,294 but this
measurement is more technically demanding.
LV wall stress may also be estimated from blood pressure
and echocardiographic measurements. However, such wall
stress measurements are difficult to reproduce, have methodological and conceptual problems, and should not be used for
diagnosis or management decision making in clinical
practice.
For purposes of the subsequent discussion of management
of patients with AR, severe AR is defined as clinical and
Doppler evidence of severe regurgitation (Table 4)27 in
addition to LV cavity dilatation. If the patient is asymptomatic and leads an active lifestyle and the echocardiogram is of
good quality, no other testing is necessary. If the patient has
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Figure 4. Management strategy for patients with chronic severe aortic regurgitation.
Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is discordance between clinical findings and echocardiography. “Stable” refers to stable echocardiographic measurements. In
some centers, serial follow-up may be performed with radionuclide ventriculography (RVG) or magnetic resonance imaging (MRI) rather than echocardiography (Echo)
to assess left ventricular (LV) volume and systolic function. AVR indicates aortic valve replacement; DD, end-diastolic dimension; EF, ejection fraction; eval, evaluation; and SD, end-systolic dimension.
severe AR and is sedentary or has equivocal symptoms,
exercise testing is helpful to assess functional capacity,
symptomatic responses, and hemodynamic effects of exercise
(Fig. 4). If the echocardiogram is of insufficient quality to
assess LV function, radionuclide angiography or cardiac
magnetic resonance should be used in asymptomatic patients
to measure LV ejection fraction at rest and estimate LV
volumes. In patients who are symptomatic on initial evaluation, it is reasonable to proceed directly to transesophageal
echocardiography or cardiac catheterization and angiography
if the echocardiogram is of insufficient quality to assess LV
function or severity of AR.
The exercise ejection fraction and the change in ejection
fraction from rest to exercise are often abnormal, even in
asymptomatic patients268,270 –272,275,283,295–303; however, these
have not been proved to have independent diagnostic or
prognostic value when LV function at rest and severity of LV
volume overload by echocardiography are already known.
One study that did identify the LV ejection fraction response
to exercise as a predictor of symptomatic deterioration or LV
dysfunction275 included many patients with NYHA functional
class II symptoms, LV systolic dysfunction (fractional shortening as low as 18%), and severe LV dilatation (end-diastolic
and end-systolic dimensions as high as 87 and 65 mm,
respectively). Hence, the predictive nature of this response in
asymptomatic patients with normal LV systolic function and
without severe LV dilatation has not been fully demonstrated.
3.2.3.4. Medical Therapy
Class I
1. Vasodilator therapy is indicated for chronic therapy in
patients with severe AR who have symptoms or LV
dysfunction when surgery is not recommended because
of additional cardiac or noncardiac factors. (Level of
Evidence: B)
Class IIa
1. Vasodilator therapy is reasonable for short-term therapy
to improve the hemodynamic profile of patients with
severe heart failure symptoms and severe LV dysfunction
before proceeding with AVR. (Level of Evidence: C)
Class IIb
1. Vasodilator therapy may be considered for long-term
therapy in asymptomatic patients with severe AR who
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have LV dilatation but normal systolic function. (Level
of Evidence: B)
Class III
1. Vasodilator therapy is not indicated for long-term
therapy in asymptomatic patients with mild to moderate AR and normal LV systolic function. (Level of
Evidence: B)
2. Vasodilator therapy is not indicated for long-term
therapy in asymptomatic patients with LV systolic
dysfunction who are otherwise candidates for AVR.
(Level of Evidence: C)
3. Vasodilator therapy is not indicated for long-term therapy in symptomatic patients with either normal LV
function or mild to moderate LV systolic dysfunction who
are otherwise candidates for AVR. (Level of Evidence: C)
Therapy with vasodilating agents is designed to improve
forward stroke volume and reduce regurgitant volume. These
effects should translate into reductions in LV end-diastolic
volume, wall stress, and afterload, resulting in preservation of
LV systolic function and reduction in LV mass. The acute
administration of sodium nitroprusside, hydralazine, nifedipine, or felodipine reduces peripheral vascular resistance and
results in an immediate augmentation in forward cardiac
output and a decrease in regurgitant volume.304 –313 With
nitroprusside and hydralazine, these acute hemodynamic
changes lead to a consistent reduction in end-diastolic volume
and an increase in ejection fraction.304 –306,312 This is an inconsistent finding with a single oral dose of nifedipine.308 –311
Reduced end-diastolic volume and increased ejection fraction
have also been observed in small numbers of patients receiving
long-term oral therapy with hydralazine and nifedipine for
periods of 1 to 2 years278,314; with nifedipine, these effects are
associated with a reduction in LV mass.272,314 Less consistent results have been reported with ACE inhibitors,
depending on the degree of reduction in arterial pressure
and end-diastolic volume.315–317 Reduced blood pressure
with enalapril and quinapril has been associated with
decreases in end-diastolic volume and mass but no change
in ejection fraction.316,317
There are 3 potential uses of vasodilating agents in chronic
AR. It should be emphasized that these criteria apply only to
patients with severe AR. The first is long-term treatment of
patients with severe AR who have symptoms and/or LV dysfunction who are considered poor candidates for surgery because
of additional cardiac or noncardiac factors. The second is
improvement in the hemodynamic profile of patients with severe
heart failure symptoms and severe LV dysfunction with shortterm vasodilator therapy before proceeding with AVR. In such
patients, vasodilating agents with negative inotropic effects
should be avoided. The third is prolongation of the compensated
phase of asymptomatic patients who have volume-loaded left
ventricles but normal systolic function.
Whether this latter effect can be achieved has been investigated in only 2 studies. The first study compared long-acting
nifedipine versus digoxin in a prospective randomized
trial.272 Over a 6-year period, fewer patients randomized to
nifedipine required AVR because of symptoms or develop-
ment of LV dysfunction (ejection fraction less than 0.50).
This study enrolled a relatively small number of patients (143
patients); there were relatively few end points (20 patients in
the digoxin group and 6 in the nifedipine group underwent
AVR); and there was no placebo control group. A more
recent study compared placebo, long-acting nifedipine, and
enalapril in 95 consecutive patients, who were followed for 7
years.277 Neither nifedipine nor enalapril reduced the development of symptoms or LV dysfunction warranting AVR
compared with placebo. Moreover, neither drug significantly
altered LV dimension, ejection fraction, or mass over the
course of time compared with placebo. Thus, definitive
recommendations regarding the indications for long-acting
nifedipine or ACE inhibitors cannot be made at this time.
If vasodilator therapy is used, the goal is to reduce systolic
blood pressure, and drug dosage should be increased until
there is a measurable decrease in systolic blood pressure or
the patient develops side effects. It is rarely possible to decrease
systolic blood pressure to normal because of the increased LV
stroke volume, and drug dosage should not be increased excessively in an attempt to achieve this goal. Vasodilator therapy is
of unknown benefit and is not indicated in patients with normal
blood pressure or normal LV cavity size.
Vasodilator therapy is not recommended for asymptomatic
patients with mild or moderate AR and normal LV function in
the absence of systemic hypertension, because these patients
have an excellent outcome with no therapy. In patients with
severe AR, vasodilator therapy is not an alternative to surgery
in asymptomatic or symptomatic patients with LV systolic
dysfunction; such patients should be considered surgical
candidates rather than candidates for long-term medical
therapy unless AVR is not recommended because of additional cardiac or noncardiac factors. Whether symptomatic
patients who have preserved systolic function can be treated
safely with aggressive medical management and whether
aggressive medical management is as good or better than
AVR have not been determined. It is recommended that
symptomatic patients undergo surgery rather than long-term
medical therapy.
There is scant information about long-term therapy with
drugs other than vasodilators in asymptomatic patients with
severe AR and normal LV function. Thus, there are no data to
support the long-term use of digoxin, diuretics, nitrates, or
positive inotropic agents in asymptomatic patients and no data
with regard to any drug in patients with mild or moderate AR.
3.2.3.5. Physical Activity and Exercise
There are no data suggesting that exercise, particularly
strenuous periodic exercise, will contribute to or accelerate
the progression of LV dysfunction in AR. Asymptomatic
patients with normal LV systolic function may participate in
all forms of normal daily physical activity, including mild
forms of exercise and in some cases competitive athletics.
Isometric exercise should be avoided. Recommendations
regarding participation in competitive athletics were published by the Task Force on Acquired Valvular Heart Disease
of the 36th Bethesda Conference.138 Before participation in
athletics, exercise testing to at least the level of exercise
required by the proposed activity is recommended so that the
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patient’s tolerance for this degree of exercise can be evaluated. This does not necessarily evaluate the long-term effects
of strenuous exercise, which are unknown.
3.2.3.6. Serial Testing
The aim of serial evaluation of asymptomatic patients with
chronic AR is to detect the onset of symptoms and objectively
assess changes in LV size and function that can occur in the
absence of symptoms. In general, the stability and chronicity
of the regurgitant lesion and the LV response to volume load
need to be established when the patient first presents to the
physician, especially if AR is moderate to severe. If the
chronic nature of the lesion is uncertain and the patient does
not present initially with one of the indications for surgery,
repeat physical examination and echocardiography should be
performed within 2 to 3 months after the initial evaluation to
ensure that a subacute process with rapid progression is not
under way. Once the chronicity and stability of the process
has been established, the frequency of clinical re-evaluation
and repeat noninvasive testing depends on the severity of the
valvular regurgitation, the degree of LV dilatation, the level
of systolic function, and whether previous serial studies have
revealed progressive changes in LV size or function (Fig. 4).
In most patients, serial testing during the long-term follow-up
period should include a detailed history, physical examination, and echocardiography. Serial chest X-rays and ECGs
have less value but are helpful in selected patients.
Asymptomatic patients with mild AR, little or no LV
dilatation, and normal LV systolic function can be seen on a
yearly basis, with instructions to alert the physician if
symptoms develop in the interim. Yearly echocardiography is
not necessary unless there is clinical evidence that regurgitation has worsened. Routine echocardiography can be performed every 2 to 3 years in such patients.
Asymptomatic patients with normal systolic function but
severe AR and significant LV dilatation (end-diastolic dimension greater than 60 mm) require more frequent and careful
re-evaluation, with a history and physical examination every
6 months and echocardiography every 6 to 12 months,
depending on the severity of dilatation and stability of
measurements. If patients are stable, echocardiographic measurements are not required more frequently than every 12
months. In patients with more advanced LV dilatation (enddiastolic dimension greater than 70 mm or end-systolic
dimension greater than 50 mm), for whom the risk of
developing symptoms or LV dysfunction ranges between
10% and 20% per year,271,272 it is reasonable to perform serial
echocardiograms as frequently as every 4 to 6 months. Serial
chest X-rays and ECGs have less value but are helpful in
selected patients.
Chronic AR may develop from disease processes that
involve the proximal ascending aorta. In patients with aortic
root dilatation, serial echocardiograms are indicated to evaluate aortic root size, as well as LV size and function. This is
discussed in Section 3.2.4.
Repeat echocardiograms are also recommended when the
patient has onset of symptoms, there is an equivocal history
of changing symptoms or changing exercise tolerance, or
there are clinical findings that suggest worsening regurgita-
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tion or progressive LV dilatation. Patients with echocardiographic evidence of progressive ventricular dilatation or
declining systolic function have a greater likelihood of
developing symptoms or LV dysfunction271 and should have
more frequent follow-up examinations (every 6 months) than
those with stable LV function.
In some centers with expertise in nuclear cardiology, serial
radionuclide ventriculograms to assess LV volume and function at rest may be an accurate and cost-effective alternative
to serial echocardiograms. However, there is no justification
for routine serial testing with both an echocardiogram and a
radionuclide ventriculogram. Serial radionuclide ventriculograms are also recommended in patients with suboptimal
echocardiograms, patients with suggestive but not definite
echocardiographic evidence of LV systolic dysfunction, and
patients for whom there is discordance between clinical
assessment and echocardiographic data. In centers with specific expertise in cardiac magnetic resonance imaging, serial
magnetic resonance imaging may be performed in place of
radionuclide angiography for the indications listed above. In
addition to accurate assessment of LV volume, mass, wall
thickness, and systolic function,318 –322 cardiac magnetic resonance imaging may be used to quantify the severity of
valvular regurgitation.323–327
Serial exercise testing is also not recommended routinely
in asymptomatic patients with preserved systolic function;
however, exercise testing may be invaluable to assess functional capacity and symptomatic responses in patients with
equivocal changes in symptomatic status. Serial exercise
imaging studies to assess LV functional reserve are not
indicated in asymptomatic patients or those in whom symptoms develop.
3.2.3.7. Indications for Cardiac Catheterization
Class I
1. Cardiac catheterization with aortic root angiography
and measurement of LV pressure is indicated for
assessment of severity of regurgitation, LV function, or
aortic root size when noninvasive tests are inconclusive
or discordant with clinical findings in patients with
AR. (Level of Evidence: B)
2. Coronary angiography is indicated before AVR in
patients at risk for CAD. (Level of Evidence: C)
Class III
1. Cardiac catheterization with aortic root angiography
and measurement of LV pressure is not indicated for
assessment of LV function, aortic root size, or severity
of regurgitation before AVR when noninvasive tests
are adequate and concordant with clinical findings and
coronary angiography is not needed. (Level of Evidence: C)
2. Cardiac catheterization with aortic root angiography
and measurement of LV pressure is not indicated for
assessment of LV function and severity of regurgitation in asymptomatic patients when noninvasive tests
are adequate. (Level of Evidence: C)
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Cardiac catheterization is not required in patients with
chronic AR unless there are questions about the severity of
AR, hemodynamic abnormalities, or LV systolic dysfunction
that persist despite physical examination and noninvasive
testing, or unless AVR is contemplated and there is a need to
assess coronary anatomy. The indications for coronary arteriography are discussed in Section 10.2. In some patients
undergoing left-heart catheterization for coronary angiography, additional aortic root angiography and hemodynamic
measurements may provide useful supplementary data.
Hemodynamic and angiographic assessment of the severity
of AR and LV function may be necessary in some patients
being considered for surgery when there are conflicting data
between clinical assessment and noninvasive tests. Less
commonly, asymptomatic patients who are not being considered for surgery may also require invasive measurement of
hemodynamics and/or determination of severity of AR when
this information cannot be obtained accurately from noninvasive tests.
Hemodynamic measurements during exercise are occasionally helpful for determining the effect of AR on LV
function or making decisions regarding medical or surgical
therapy. In selected patients with severe AR, borderline or
normal LV systolic function, and LV chamber enlargement
that is approaching the threshold for surgery (defined below),
measurement of cardiac output and LV filling pressures at
rest and during exercise with a right-heart catheter may be
valuable for identifying patients with severe hemodynamic
abnormalities in whom surgery is warranted.
3.2.3.8. Indications for Aortic Valve Replacement or
Aortic Valve Repair
The majority of patients with severe AR requiring surgery
undergo valve replacement (see Section 7.2.). However, in
several surgical centers, there is increasing experience in
performing aortic valve replacement in selected patients (see
Section 7.2.6.). In the discussion that follows, the term
“AVR” applies to both aortic valve replacement and aortic
valve repair, with the understanding that aortic valve repair
should be considered only in those surgical centers that have
developed the appropriate technical expertise, gained experience in patient selection, and demonstrated outcomes equivalent to those of valve replacement. The indications for valve
replacement and repair do not differ.
In patients with pure, chronic AR, AVR should be considered only if AR is severe (Table 4).27 Patients with only mild
AR are not candidates for AVR, and if such patients have
symptoms or LV dysfunction, other causes should be considered, such as CAD, hypertension, or cardiomyopathic processes. If the severity of AR is uncertain after a review of
clinical and echocardiographic data, additional information
may be needed, such as invasive hemodynamic and angiographic data. The following discussion applies only to those
patients with pure, severe AR.
2. AVR is indicated for asymptomatic patients with
chronic severe AR and LV systolic dysfunction (ejection fraction 0.50 or less) at rest. (Level of Evidence: B)
3. AVR is indicated for patients with chronic severe AR
while undergoing CABG or surgery on the aorta or
other heart valves. (Level of Evidence: C)
Class IIa
1. AVR is reasonable for asymptomatic patients with severe
AR with normal LV systolic function (ejection fraction
greater than 0.50) but with severe LV dilatation (enddiastolic dimension greater than 75 mm or end-systolic
dimension greater than 55 mm).* (Level of Evidence: B)
Class IIb
1. AVR may be considered in patients with moderate AR
while undergoing surgery on the ascending aorta.
(Level of Evidence: C)
2. AVR may be considered in patients with moderate AR
while undergoing CABG. (Level of Evidence: C)
3. AVR may be considered for asymptomatic patients
with severe AR and normal LV systolic function at rest
(ejection fraction greater than 0.50) when the degree of
LV dilatation exceeds an end-diastolic dimension of 70
mm or end-systolic dimension of 50 mm, when there is
evidence of progressive LV dilatation, declining exercise tolerance, or abnormal hemodynamic responses to
exercise.* (Level of Evidence: C)
Class III
1. AVR is not indicated for asymptomatic patients with
mild, moderate, or severe AR and normal LV systolic
function at rest (ejection fraction greater than 0.50)
when degree of dilatation is not moderate or severe
(end-diastolic dimension less than 70 mm, end-systolic
dimension less than 50 mm).* (Level of Evidence: B)
3.2.3.8.1. Symptomatic Patients With Normal Left Ventricular Systolic Function. AVR is indicated in patients with
normal LV systolic function (defined as ejection fraction
greater than 0.50 at rest) who have NYHA functional class III
or IV symptoms. Patients with Canadian Heart Association
functional class II to IV angina pectoris should also be
considered for surgery. In many patients with NYHA functional class II dyspnea, the cause of symptoms is often
unclear, and clinical judgment is required. Patients with
well-compensated AR often have chronic mild dyspnea or
fatigue, and it may be difficult to differentiate the effects of
deconditioning or aging from true cardiac symptoms. In such
patients, exercise testing may be valuable. If the cause of
these mild symptoms is uncertain and they are not severe
enough to interfere with the patient’s lifestyle, a period of
observation may be reasonable. However, new onset of mild
dyspnea has different implications in severe AR, especially in
patients with increasing LV chamber size or evidence of
Class I
1. AVR is indicated for symptomatic patients with severe
AR irrespective of LV systolic function. (Level of
Evidence: B)
*Consider lower threshold values for patients of small stature of either
gender.
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declining LV systolic function into the low normal range.
Thus, even if patients have not achieved the threshold values
of LV size and function recommended for surgery in asymptomatic patients, development of mild symptoms is an indication for AVR in a patient who is nearing these values.
3.2.3.8.2. Symptomatic Patients With Left Ventricular Dysfunction. Patients with NYHA functional class II, III, or IV
symptoms and with mild to moderate LV systolic dysfunction
(ejection fraction 0.25 to 0.50) should undergo AVR. Patients
with NYHA functional class IV symptoms have worse
postoperative survival rates and lower likelihood of recovery
of systolic function than patients with less severe symptoms,245,250,252,254 but AVR will improve ventricular loading
conditions and expedite subsequent management of LV
dysfunction.238
Severely symptomatic patients (NYHA functional class
IV) with advanced LV dysfunction (ejection fraction less than
0.25 and/or end-systolic dimension greater than 60 mm)
present difficult management issues. Some patients will manifest meaningful recovery of LV function after AVR, but
many will have developed irreversible myocardial changes.
The mortality associated with valve replacement approaches
10%, and postoperative mortality over the subsequent few
years is high. Valve replacement should be considered more
strongly in patients with NYHA functional class II and III
symptoms, especially if
• symptoms and evidence of LV dysfunction are of recent
onset;
• intensive short-term therapy with vasodilators and diuretics results in symptomatic improvement;
• intravenous positive inotropic agents result in substantial
improvement in hemodynamics or systolic function.
However, even in patients with NYHA functional class IV
symptoms and ejection fraction less than 0.25, the high risks
associated with AVR and subsequent medical management of
LV dysfunction are usually a better alternative than the higher
risks of long-term medical management alone.328
3.2.3.8.3. Asymptomatic Patients. AVR in asymptomatic patients remains a controversial topic, but it is generally
agreed233,329 –335 that AVR is indicated in patients with LV
systolic dysfunction. As noted previously, for the purposes of
these guidelines, LV systolic dysfunction is defined as an
ejection fraction below normal at rest. The lower limit of
normal will be assumed to be 0.50, with the realization that
this lower limit is technique dependent and may vary among
institutions. The committee also realizes that there may be
variability in any given measurement of LV dimension or
ejection fraction. Therefore, the committee recommends that
2 consecutive measurements be obtained before one proceeds
with a decision to recommend surgery in the asymptomatic
patient. These consecutive measurements could be obtained
with the same test repeated in a short time period (such as a
second echocardiogram after an initial echocardiogram) or
with a separate, independent test (e.g., radionuclide ventriculography, magnetic resonance imaging, or contrast left ventriculography after an initial echocardiogram).
AVR is also recommended in patients with severe LV
dilatation (end-diastolic dimension greater than 75 mm or
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end-systolic dimension greater than 55 mm), even if ejection
fraction is normal. The majority of patients with this degree
of dilatation will have already developed systolic dysfunction
because of afterload mismatch and will thus be candidates for
valve replacement on the basis of the depressed ejection
fraction. The elevated end-systolic dimension in this regard is
often a surrogate for systolic dysfunction. The relatively
small number of asymptomatic patients with preserved ejection fraction despite severe increases in end-systolic and
end-diastolic chamber size should be considered for surgery,
because they appear to represent a high-risk group with an
increased incidence of sudden death,271,336 and the results of
valve replacement in such patients have thus far been excellent.264 In contrast, postoperative mortality is considerable
once patients with severe LV dilatation develop symptoms or
LV systolic dysfunction.264 The recommendations regarding
the risk of sudden death and postoperative outcome with
severe LV dilatation were based on reports of sudden death in
2 of 3 patients with an LV end-diastolic dimension greater
than 80 mm271 and 2 patients with an LV end-diastolic
volume index greater than 200 ml/m2.336 It should be recognized, however, that LV end-diastolic dimension, whether
examined as a continuous or as a dichotomous variable (less
than 80 vs. greater than 80 mm), has not been found to be
predictive of postoperative survival or LV function, whereas
ejection fraction is predictive. Conservatively managed patients with an end-diastolic dimension exceeding 70 mm
likewise exhibit a favorable clinical outcome.276 These data
do not strongly support the use of extreme LV enlargement as
an indication for AVR, unless cardiac symptoms or systolic
dysfunction is present.337 However, the committee recommends surgery before the left ventricle achieves an extreme
degree of dilatation and recommends AVR for patients with
LV end-diastolic dimension greater than 75 mm.
Anthropometric normalization of LV end-diastolic dimension (or volume) should be considered, but unfortunately,
there is lack of agreement as to whether or not normalization
based on body surface area or body mass index is predictive
of outcome.288,338 Normalization of end-diastolic dimension
for body surface area tends to mask the diagnosis of LV
enlargement, especially in patients who are overweight.339
The use of height and a consideration of gender are likely to
be more appropriate than body surface area.340
Patients with severe AR in whom the degree of LV
dilatation has not reached but is approaching these threshold
values (e.g., LV end-diastolic dimension of 70 to 75 mm or
end-systolic dimension of 50 to 55 mm) should be followed
with frequent echocardiograms every 4 to 6 months, as noted
previously (Fig. 4). In addition, AVR may be considered in
such patients if there is evidence of declining exercise
tolerance or abnormal hemodynamic responses to exercise,
for example, an increase in pulmonary artery wedge pressure
greater than 25 mm Hg with exercise.
Several patient subgroups develop LV systolic dysfunction
with less marked LV dilatation than observed in the majority
of patients with uncomplicated AR. These include patients
with long-standing hypertension in whom the pressureoverloaded ventricle has reduced compliance and a limited
potential to increase its chamber size; patients with concom-
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itant CAD, in whom myocardial ischemia may develop with
increasing myocardial wall stress, resulting in LV dysfunction; and patients with concomitant MS, in whom the left
ventricle will not dilate to the same extent as in patients with
pure AR.341 In such patients, it is particularly important that
LV ejection fraction and not merely systolic dimension be
monitored. Women also tend to develop symptoms and LV
dysfunction with less LV dilatation than men338; this appears
to be related to body size, because these differences are not
apparent when LV dimensions are corrected for body surface
area. Hence, LV dimensions alone may be misleading in
small patients of either gender, and the threshold values of
end-diastolic and end-systolic dimension recommended
above for AVR in asymptomatic patients (75 and 55 mm,
respectively) may need to be reduced in such patients. There
are no data with which to derive guidelines for LV dimensions corrected for body size, and clinical judgment is
required.
A decrease in ejection fraction during exercise should not
be used as the only indication for AVR in asymptomatic
patients with normal LV systolic function at rest, because the
exercise ejection fraction response is multifactorial, and the
strength of evidence is limited. The ejection fraction response
to exercise has not proved to have independent prognostic
value in patients undergoing surgery.254 The change in
ejection fraction with exercise is a relatively nonspecific
response related to both severity of volume load271,296,300,301
and exercise-induced changes in preload and peripheral
resistance280 that develop early in the natural history of AR.
AVR should also not be recommended in asymptomatic
patients with normal systolic function merely because of
evidence of LV dilatation as long as the dilatation is not
severe (end-diastolic dimension less than 75 mm or endsystolic dimension less than 55 mm).
Patients who demonstrate progression of LV dilatation or
progressive decline in ejection fraction on serial studies
represent a higher-risk group who require careful monitoring,271 but such patients often reach a new steady state and
may do well for extended periods of time. Hence, AVR is not
recommended until the threshold values noted above are
reached or symptoms or LV systolic dysfunction develop.
However, prompt referral to AVR once patients develop
symptoms, subnormal ejection fraction, or progressive LV
dilatation results in significantly better postoperative survival
than if AVR is delayed until symptoms or LV systolic
function becomes more severe.254,265,267
The surgical options for treating AR are expanding, with
growing experience in aortic homografts, pulmonary autografts, unstented tissue valves, and aortic valve repair. If
these techniques are ultimately shown to improve long-term
survival or reduce postoperative valve complications, it is
conceivable that the thresholds for recommending AVR may
be reduced. Until such data are available, the indications for
surgery for AR should not vary with the operative technique
to be used.
3.2.4. Concomitant Aortic Root Disease
In addition to causing acute AR, diseases of the proximal
aorta may also contribute to chronic AR. Dilatation of the
ascending aorta is among the most common causes of isolated
AR.342 In such patients, the valvular regurgitation may be less
important in decision making than the primary disease of the
aorta, such as Marfan syndrome, dissection, or chronic
dilatation of the aortic root related to hypertension or a
bicuspid aortic valve (see Section 3.3). In such patients, if the
AR is mild or the left ventricle is only mildly dilated,
management should focus on treating the underlying aortic
root disease. In many patients, however, AR may be severe
and associated with severe LV dilatation or systolic dysfunction, in which case decisions regarding medical therapy and
timing of the operation must consider both conditions. In
general, AVR and aortic root reconstruction are indicated in
patients with disease of the aortic root or proximal aorta and
AR of any severity when the degree of dilatation of the aorta
or aortic root reaches or exceeds 5.0 cm by echocardiography.343 However, some have recommended surgery at a lower
level of dilatation (4.5 cm) or based on a rate of increase of
0.5 cm per year or greater in surgical centers with established
expertise in repair of the aortic root and ascending aorta.344
Aortic root and ascending aorta dilation in patients with
bicuspid aortic valves is discussed in greater detail in Section
3.3.
3.2.5. Evaluation of Patients After
Aortic Valve Replacement
After AVR, close follow-up is necessary during the early and
long-term postoperative course to evaluate prosthetic valve
function and assess LV function, as discussed in Sections 9.3.
to 9.3.3. An echocardiogram should be performed soon after
surgery to assess the results of surgery on LV size and
function and to serve as a baseline against which subsequent
echocardiograms may be compared. This could be performed
either before hospital discharge or preferably at the first
outpatient re-evaluation. Within the first few weeks of surgery, there is little change in LV systolic function, and
ejection fraction may even deteriorate compared with preoperative values because of the reduced preload,345 even though
ejection fraction may increase over the subsequent several
months. Thus, persistent or more severe systolic dysfunction
early after AVR is a poor predictor of subsequent improvement in LV function in patients with preoperative LV
dysfunction. A better predictor of subsequent LV systolic
function is the reduction in LV end-diastolic dimension,
which declines significantly within the first week or 2 after
AVR.240,245,346 This is an excellent marker of the functional
success of valve replacement, because 80% of the overall
reduction in end-diastolic dimension observed during the
long-term postoperative course occurs within the first 10 to
14 days after AVR,240,245,346 and the magnitude of reduction
in end-diastolic dimension after surgery correlates with the
magnitude of increase in ejection fraction.245
After the initial postoperative re-evaluation, the patient
should be seen and examined again at 6 and 12 months and
then on a yearly basis if the clinical course is uncomplicated.
If the patient is asymptomatic, the early postoperative echocardiogram demonstrates substantial reduction in LV enddiastolic dimension, and LV systolic function is normal,
serial postoperative echocardiograms after the initial early
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postoperative study are usually not indicated. However,
repeat echocardiography is warranted at any point at which
there is evidence of a new murmur, questions of prosthetic
valve integrity, or concerns about LV function. Patients with
persistent LV dilatation on the initial postoperative echocardiogram should be treated as would any other patient with
symptomatic or asymptomatic LV dysfunction, including
treatment with ACE inhibitors and beta-adrenergic blocking
agents. In such patients, repeat echocardiography to assess
LV size and systolic function is warranted at the 6- and
12-month re-evaluations. If LV dysfunction persists beyond
this time frame, repeat echocardiograms should be performed
as clinically indicated. Management of patients after AVR is
discussed in greater detail in Section 9.3.
3.2.6. Special Considerations in the Elderly
The vast majority of elderly patients with aortic valve disease
have AS or combined AS and AR, and pure AR is uncommon.347 Elderly patients with AR generally fare less well than
patients who are young or middle-aged. Patients older than 75
years are more likely to develop symptoms or LV dysfunction
at earlier stages of LV dilatation, have more persistent
ventricular dysfunction and heart failure symptoms after
surgery, and have worse postoperative survival rates than
their younger counterparts. Many such patients have concomitant CAD, which must be considered in the evaluation of
symptoms, LV dysfunction, and indications for surgery.
Because the goal of therapy is to improve the quality of life
rather than longevity, symptoms are the most important guide
to determining whether or not AVR should be performed.
Nonetheless, asymptomatic or mildly symptomatic patients
who develop LV dysfunction (as defined previously) should
be considered for AVR if the risks of surgery are balanced in
otherwise healthy patients against the expected improvement
in long-term outcome.
3.3. Bicuspid Aortic Valve With Dilated
Ascending Aorta
Class I
1. Patients with known bicuspid aortic valves should
undergo an initial transthoracic echocardiogram to
assess the diameters of the aortic root and ascending
aorta. (Level of Evidence: B)
2. Cardiac magnetic resonance imaging or cardiac computed tomography is indicated in patients with bicuspid aortic valves when morphology of the aortic root or
ascending aorta cannot be assessed accurately by echocardiography. (Level of Evidence: C)
3. Patients with bicuspid aortic valves and dilatation of
the aortic root or ascending aorta (diameter greater
than 4.0 cm*) should undergo serial evaluation of
aortic root/ascending aorta size and morphology by
echocardiography, cardiac magnetic resonance, or
computed tomography on a yearly basis. (Level of
Evidence: C)
*Consider lower threshold values for patients of small stature of either
gender.
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4. Surgery to repair the aortic root or replace the ascending
aorta is indicated in patients with bicuspid aortic valves if
the diameter of the aortic root or ascending aorta is
greater than 5.0 cm* or if the rate of increase in diameter
is 0.5 cm per year or more. (Level of Evidence: C)
5. In patients with bicuspid valves undergoing AVR because
of severe AS or AR (see Sections 3.1.7 and 3.2.3.8), repair
of the aortic root or replacement of the ascending aorta is
indicated if the diameter of the aortic root or ascending
aorta is greater than 4.5 cm.* (Level of Evidence: C)
Class IIa
1. It is reasonable to give beta-adrenergic blocking agents
to patients with bicuspid valves and dilated aortic roots
(diameter greater than 4.0 cm*) who are not candidates for surgical correction and who do not have
moderate to severe AR. (Level of Evidence: C)
2. Cardiac magnetic resonance imaging or cardiac computed
tomography is reasonable in patients with bicuspid aortic
valves when aortic root dilatation is detected by echocardiography to further quantify severity of dilatation and involvement of the ascending aorta. (Level of Evidence: B)
There is growing awareness that many patients with bicuspid
aortic valves have disorders of vascular connective tissue,
involving loss of elastic tissue,348,349 which may result in
dilatation of the aortic root or ascending aorta even in the
absence of hemodynamically significant AS or AR.350 –353
Aortic root or ascending aortic dilatation can progress with
time in this condition.354 These patients have a risk of aortic
dissection that is related to the severity of dilatation.349,355–357
Recommendations for athletic participation in patients with
bicuspid valve disease and associated dilatation of the aortic
root or ascending aorta from the 36th Bethesda Conference138
are based on limited data but with the understanding that
aortic dissection can occur in some patients with aortic root or
ascending aorta diameters less than 50 mm.344,356,358 Therapy
with beta-adrenergic blocking agents might be effective in
slowing the progression of aortic dilatation, but the available
data have been developed in patients with Marfan syndrome359 and not in patients with bicuspid aortic valves.
Echocardiography remains the primary imaging technique
for identifying those patients in whom the aortic root or
ascending aorta is enlarged. In many cases, echocardiography, including transesophageal imaging, provides all of the
necessary information required to make management decisions. More accurate quantification of the diameter of the
aortic root and ascending aorta, as well as full assessment of
the degree of enlargement, can be obtained with cardiac
magnetic resonance imaging or computed tomography. These
techniques also allow for an accurate depiction of the size and
contour of the aorta in its arch, descending thoracic, and
abdominal segments. When the findings on transthoracic
echocardiography relative to the aortic root and ascending
aorta are concordant with those of either cardiac magnetic
resonance or computed tomographic imaging, then transthoracic echocardiography can be used for annual surveillance.
The dimensions of the aortic root and ascending aorta show
considerable variability in normal populations. Regression
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formulas and nomograms have been developed for adolescents and adults that account for age and body surface area.360
An upper limit of 2.1 cm per m2 has been established at the
level of the aortic sinuses. Dilatation is considered an increase
in diameter above the norm for age and body surface area,
and an aneurysm has been defined as a 50% increase over the
normal diameter.361
Surgery to repair the aortic root or replace the ascending
aorta has been recommended for those patients with greatly
enlarged aortic roots or ascending aortas.344,349,357,358 In recommending elective surgery for this condition, a number of
factors must be considered, including the patient’s age, the
relative size of the aorta and aortic root, the structure and
function of the aortic valve, and the experience of the surgical
team. Aortic valve-sparing operations are feasible in most
patients with dilatation of the aortic root or ascending aorta
who do not have significant AR or aortic valve calcification.362–364 It is recommended that patients with bicuspid
valves should undergo elective repair of the aortic root or
replacement of the ascending aorta if the diameter of these
structures exceeds 5.0 cm. Such surgery should be performed
by a surgical team with established expertise in these procedures. Others have recommended a value of 2.5 cm per m2 or
greater as the indication for surgery.365 If patients with
bicuspid valves and associated aortic root enlargement undergo AVR because of severe AS or AR (Sections 3.1.7. and
3.2.3.8.), it is recommended that repair of the aortic root or
replacement of the ascending aorta be performed if the
diameter of these structures is greater than 4.5 cm.366
3.4. Mitral Stenosis
3.4.1. Pathophysiology and Natural History
MS is an obstruction to LV inflow at the level of the MV as
a result of a structural abnormality of the MV apparatus,
which prevents proper opening during diastolic filling of the
left ventricle. The predominant cause of MS is rheumatic
carditis. Isolated MS occurs in 40% of all patients presenting
with rheumatic heart disease, and a history of rheumatic fever
can be elicited from approximately 60% of patients presenting with pure MS.367,368 The ratio of women to men presenting with isolated MS is 2:1.367–369 Congenital malformation of
the MV occurs rarely and is observed mainly in infants and
children.370 Acquired causes of MV obstruction, other than
rheumatic heart disease, are rare. These include left atrial
myxoma, ball valve thrombus, mucopolysaccharidosis, and severe annular calcification.
In patients with MS due to rheumatic fever, the pathological process causes leaflet thickening and calcification, commissural fusion, chordal fusion, or a combination of these
processes.370,371 The result is a funnel-shaped mitral apparatus
in which the orifice of the mitral opening is decreased in size.
Interchordal fusion obliterates the secondary orifices, and
commissural fusion narrows the principal orifice.370,371
The normal MV area is 4.0 to 5.0 cm2. Narrowing of the
valve area to less than 2.5 cm2 typically occurs before the
development of symptoms.139 With a reduction in valve area
by the rheumatic process, blood can flow from the left atrium
to the left ventricle only if propelled by a pressure gradient.
This diastolic transmitral gradient is the fundamental expres-
sion of MS372 and results in elevation of left atrial pressure,
which is reflected back into the pulmonary venous circulation. Decreased pulmonary venous compliance that results in
part from an increased pulmonary endothelin-1 spillover rate
may also contribute to increased pulmonary venous pressure.373 Increased pressure and distension of the pulmonary
veins and capillaries can lead to pulmonary edema as pulmonary
venous pressure exceeds that of plasma oncotic pressure. In
patients with chronic MV obstruction, however, even when it is
severe and pulmonary venous pressure is very high, pulmonary
edema may not occur owing to a marked decrease in pulmonary
microvascular permeability. The pulmonary arterioles may react
with vasoconstriction, intimal hyperplasia, and medial hypertrophy, which lead to pulmonary arterial hypertension.
An MV area greater than 1.5 cm2 usually does not produce
symptoms at rest.374 However, if there is an increase in
transmitral flow or a decrease in the diastolic filling period,
there will be a rise in left atrial pressure and development of
symptoms. From hydraulic considerations, at any given
orifice size, the transmitral gradient is a function of the square
of the transvalvular flow rate and is dependent on the diastolic
filling period.139 Thus, the first symptoms of dyspnea in
patients with mild MS are usually precipitated by exercise,
emotional stress, infection, pregnancy, or atrial fibrillation
with a rapid ventricular response.374 As the obstruction across
the MV increases, decreasing effort tolerance occurs.
As the severity of stenosis increases, cardiac output becomes subnormal at rest374 and fails to increase during
exercise.375 The degree of pulmonary vascular disease is also
an important determinant of symptoms in patients with
MS.373,374,376 A second obstruction to flow develops from
increased pulmonary arteriolar resistance,376,377 which may
protect the lungs from pulmonary edema.376,377 In some
patients, an additional reversible obstruction develops at the
level of the pulmonary veins.378,379 The low cardiac output
and increased pulmonary arteriolar resistance, which results
from functional and structural changes (alveolar basement
membrane thickening, adaptation of neuroreceptors, increased lymphatic drainage, and increased transpulmonary
endothelin spillover rate), contribute to the ability of a patient
with severe MS to remain minimally symptomatic for prolonged periods of time.374,376,377
The natural history of patients with untreated MS has been
defined from studies in the 1950s and 1960s.367–369 Mitral
stenosis is a continuous, progressive, lifelong disease, usually
consisting of a slow, stable course in the early years followed
by a progressive acceleration later in life.367–369,380 In developed countries, there is a long latent period of 20 to 40 years
from the occurrence of rheumatic fever to the onset of
symptoms. Once symptoms develop, there is another period
of almost a decade before symptoms become disabling.367
Overall, the 10-year survival of untreated patients presenting
with MS is 50% to 60%, depending on symptoms at presentation.368,369 In the asymptomatic or minimally symptomatic
patient, survival is greater than 80% at 10 years, with 60% of
patients having no progression of symptoms.368,369,380 However, once significant limiting symptoms occur, there is a
dismal 0% to 15% 10-year survival rate.367–369,380,381 Once
there is severe pulmonary hypertension, mean survival drops
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to less than 3 years.382 The mortality of untreated patients
with MS is due to progressive pulmonary and systemic
congestion in 60% to 70%, systemic embolism in 20% to
30%, pulmonary embolism in 10%, and infection in 1% to
5%.369,370 In North America and Europe, this classic history
of MS has been replaced by an even milder delayed course
with the decline in incidence of rheumatic fever.380,383 The
mean age of presentation is now in the fifth to sixth decade380,383;
more than one third of patients undergoing valvotomy are older
than 65 years.384 In some geographic areas, MS progresses more
rapidly, presumably due to either a more severe rheumatic insult
or repeated episodes of rheumatic carditis due to new streptococcal infections, resulting in severe symptomatic MS in the late
teens and early 20s.380 Serial hemodynamic and Dopplerechocardiographic studies have reported annual loss of MV area
ranging from 0.09 to 0.32 cm2.385,386
Although MS is best described as a disease continuum, and
there is no single value that defines severity, for these
guidelines, MS severity is based on a variety of hemodynamic
and natural history data (Table 4)27 using mean gradient,
pulmonary artery systolic pressure, and valve area as follows:
mild (area greater than 1.5 cm2, mean gradient less than 5 mm
Hg, or pulmonary artery systolic pressure less than 30 mm Hg),
moderate (area 1.0 to 1.5 cm2, mean gradient 5 to 10 mm Hg, or
pulmonary artery systolic pressure 30 to 50 mm Hg), and severe
(area less than 1.0 cm2, mean gradient greater than 10 mm Hg,
or pulmonary artery systolic pressure greater than 50 mm Hg).
3.4.2. Indications for Echocardiography in Mitral Stenosis
Class I
1. Echocardiography should be performed in patients for
the diagnosis of MS, assessment of hemodynamic severity
(mean gradient, MV area, and pulmonary artery pressure),
assessment of concomitant valvular lesions, and assessment
of valve morphology (to determine suitability for percutaneous mitral balloon valvotomy). (Level of Evidence: B)
2. Echocardiography should be performed for reevaluation in patients with known MS and changing
symptoms or signs. (Level of Evidence: B)
3. Echocardiography should be performed for assessment of the hemodynamic response of the mean
gradient and pulmonary artery pressure by exercise
Doppler echocardiography in patients with MS when
there is a discrepancy between resting Doppler
echocardiographic findings, clinical findings, symptoms, and signs. (Level of Evidence: C)
4. Transesophageal echocardiography in MS should be
performed to assess the presence or absence of left
atrial thrombus and to further evaluate the severity of
MR in patients considered for percutaneous mitral
balloon valvotomy. (Level of Evidence: C)
5. Transesophageal echocardiography in MS should be performed to evaluate MV morphology and hemodynamics
in patients when transthoracic echocardiography provides suboptimal data. (Level of Evidence: C)
Class IIa
1. Echocardiography is reasonable in the re-evaluation of
asymptomatic patients with MS and stable clinical find-
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ings to assess pulmonary artery pressure (for those with
severe MS, every year; moderate MS, every 1 to 2 years;
and mild MS, every 3 to 5 years). (Level of Evidence: C)
Class III
1. Transesophageal echocardiography in the patient with
MS is not indicated for routine evaluation of MV morphology and hemodynamics when complete transthoracic
echocardiographic data are satisfactory. (Level of Evidence: C)
The diagnosis of MS should be made on the basis of the
history, physical examination, chest X-ray, and ECG (Fig. 5).
Patients may present with no symptoms but have an abnormal
physical examination.380,383 Although some patients may
present with fatigue, dyspnea, or frank pulmonary edema, in
others, the initial manifestation of MS is the onset of atrial
fibrillation or an embolic event.367 Rarely, patients may
present with hemoptysis, hoarseness, or dysphagia. The
characteristic auscultatory findings of rheumatic MS are
accentuated first heart sound (S1), opening snap (OS), lowpitched middiastolic rumble, and a presystolic murmur. These
findings, however, may also be present in patients with
nonrheumatic MV obstruction (e.g., left atrial myxoma) and
may be absent with severe pulmonary hypertension, low
cardiac output, and a heavily calcified immobile MV. A
shorter A2-OS interval and longer duration of diastolic
rumble indicates more severe MS. An A2-OS interval of less
than 0.08 seconds implies severe MS.387 Physical findings of
pulmonary hypertension, such as a loud P2 or right ventricular
(RV) heave, also suggest severe MS.
The diagnostic tool of choice in the evaluation of a patient
with MS is 2D and Doppler echocardiography.388 –393 Echocardiography is able to identify restricted diastolic opening of
the MV leaflets due to “doming” of the anterior leaflet and
immobility of the posterior leaflet.388,390,392,393 Other entities
that can simulate the clinical features of rheumatic MS, such
as left atrial myxoma, mucopolysaccharidosis, nonrheumatic
calcific MS, cor triatriatum, and a parachute MV, can be
readily identified by 2D echocardiography. Planimetry of the
orifice area may be possible from the short-axis view.
Two-dimensional echocardiography can be used to assess the
morphological appearance of the MV apparatus, including
leaflet mobility and flexibility, leaflet thickness, leaflet calcification, subvalvular fusion, and the appearance of commissures.391,394 –398 These features may be important when one
considers the timing and type of intervention to be performed.394 – 400 Patients with mobile noncalcified leaflets, no
commissural calcification, and little subvalvular fusion may
be candidates for either balloon catheter or surgical commissurotomy/valvotomy.394 –399 There are several methods used
to assess suitability for valvotomy, including a Wilkins score
(Table 17),400 an echocardiographic grouping (based on valve
flexibility, subvalvular fusion, and leaflet calcification),397
and the absence or presence of commissural calcium.398
Chamber size and function and other structural valvular,
myocardial, or pericardial abnormalities can be assessed with
the 2D echocardiographic study.
Doppler echocardiography can be used to assess the
hemodynamic severity of the obstruction.389,391,401 The mean
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Figure 5. Management strategy for patients with mitral stenosis.
*The writing committee recognizes that there may be variability in the measurement of mitral valve area (MVA) and that the mean transmitral gradients, pulmonary artery
wedge pressure (PAWP), and pulmonary artery systolic pressure (PP) should also be taken into consideration. †There is controversy as to whether patients with severe
mitral stenosis (MVA less than 1.0 cm2) and severe pulmonary hypertension (pulmonary artery pressure greater than 60 mm Hg) should undergo percutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement to prevent right ventricular failure. ‡Assuming no other cause for pulmonary hypertension is present. AF indicates atrial
fibrillation; CXR, chest X-ray; ECG, electrocardiogram; echo, echocardiography; LA, left atrial; MR, mitral regurgitation; and 2D, 2-dimensional.
Table 17.
Determinants of the Echocardiographic Mitral Valve Score
Grade
Mobility
Subvalvular Thickening
Thickening
1
Highly mobile valve with only leaflet
tips restricted
Minimal thickening just below the
mitral leaflets
Leaflets near normal in thickness
(4 to 5 mm)
A single area of increased
echo brightness
Calcification
2
Leaflet mid and base portions have
normal mobility
Thickening of chordal structures
extending up to one third of
the chordal length
Midleaflets normal, considerable
thickening of margins (5 to 8
mm)
Scattered areas of brightness
confined to leaflet margins
3
Valve continues to move forward in
diastole, mainly from the base
Thickening extending to the distal
third of the chords
Thickening extending through the
entire leaflet (5 to 8 mm)
Brightness extending into the
midportion of the leaflets
4
No or minimal forward movement
of the leaflets in diastole
Extensive thickening and
shortening of all chordal
structures extending down to
the papillary muscles
Considerable thickening of all
leaflet tissue (greater than 8 to
10 mm)
Extensive brightness
throughout much of the
leaflet tissue
Reprinted with permission from Wilkins GT, Weyman AE, Abascal VM, Block PC, Palacios IF. Percutaneous balloon dilatation of the mitral valve: an analysis of
echocardiographic variables related to outcome and the mechanism of dilatation. Br Heart J 1988;60:299 –308.400
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transmitral gradient can be accurately and reproducibly measured from the continuous-wave Doppler signal across the
MV with the modified Bernoulli equation.391,401 The MV area
can be noninvasively derived from Doppler echocardiography with either the diastolic pressure half-time method401– 404
or the continuity equation.402 The half-time method may be
inaccurate in patients with abnormalities of left atrial or LV
compliance, those with associated AR, and those who have
had mitral valvotomy.403,404 Doppler echocardiography may
also be used to estimate pulmonary artery systolic pressure
from the TR velocity signal405 and to assess severity of
concomitant MR or AR. Formal hemodynamic exercise
testing can be done noninvasively with either a supine bicycle
or upright treadmill with Doppler recordings of transmitral
and tricuspid velocities.406 – 409 This allows measurement of
both the transmitral gradient407– 409 and pulmonary artery
systolic pressure406,408 at rest and with exercise.410 The
criteria for the assessment of the severity of MS are summarized in Table 4.27 These criteria are applicable when the heart
rate is between 60 and 90 bpm.
In all patients with MS, an initial clinical history, physical
examination, ECG, and chest X-ray should be performed. 2D
and Doppler echocardiography should also be performed to
confirm the diagnosis of MS and rule out other causes of MV
obstruction and concomitant problems that would require
further therapy, that is, myocardial or other valvular heart
disease. The morphology of the MV apparatus and suitability
for valvotomy should be assessed. The severity of MS should
be determined using both the mean transmitral gradient and
valve area from the Doppler echocardiogram, and pulmonary
artery pressure should be estimated when possible. A transesophageal echocardiogram is not required unless a question
about diagnosis remains after transthoracic echocardiography.
In the asymptomatic patient who has documented mild MS
(valve area greater than 1.5 cm2 and mean gradient less than
5 mm Hg), no further investigations are needed on the initial
workup (Fig. 5). These patients usually remain stable for
years.368,369,380 If there is more significant MS, a decision to
proceed further should be based on the suitability of the
patient for mitral valvotomy. In patients with pliable, noncalcified valves with no or little subvalvular fusion, no calcification in the commissures, and no left atrial thrombus,
percutaneous mitral valvotomy can be performed with a low
complication rate and may be indicated if symptoms develop.
Because of the slowly progressive course of MS, patients may
remain “asymptomatic” with severe stenosis merely by readjusting their lifestyles to a more sedentary level. Elevated
pulmonary vascular resistance and/or low cardiac output may
also play an adaptive role in preventing congestive symptoms
from occurring in patients with severe MS.374,376,377 Elevation
of pulmonary vascular resistance is an important physiological event in MS,377 and the level of pulmonary pressure is an
indicator of the overall hemodynamic consequence. Patients
with moderate pulmonary hypertension at rest (pulmonary
artery systolic pressure greater than 50 mm Hg) and pliable
MV leaflets may be considered for percutaneous mitral
valvotomy even if they deny symptoms. In patients who lead
a sedentary lifestyle, a hemodynamic exercise test with
Doppler echocardiography is useful.406 – 409 Objective limita-
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tion of exercise tolerance with a rise in transmitral gradient
greater than 15 mm Hg and a rise in pulmonary artery systolic
pressure greater than 60 mm Hg may be an indication for
percutaneous valvotomy if the MV morphology is suitable.
There is a subset of asymptomatic patients with severe MS
(valve area less than 1.0 cm2) and severe pulmonary hypertension (pulmonary artery systolic pressure greater than 75%
of systemic pressure either at rest or with exercise). If these
patients do not have a valve morphology favorable for percutaneous mitral balloon valvotomy or surgical valve repair, it is
controversial whether MV replacement should be performed in
the absence of symptoms to prevent RV failure, but surgery is
generally recommended in such patients. However, the patient
(and the family) should be involved in the decision regarding
intervention.
3.4.3. Medical Therapy
3.4.3.1. Medical Therapy: General (Updated)
In the patient with MS, the major problem is mechanical
obstruction to inflow at the level of the MV, and no medical
therapy will specifically relieve the fixed obstruction. The LV
is protected from a volume or pressure overload, and thus, no
specific medical therapy is required in the asymptomatic
patient in normal sinus rhythm who has mild MS. Because
rheumatic fever is the primary cause of MS, prophylaxis
against rheumatic fever is recommended.
In the patient who has more than a mild degree of MS,
counseling on avoidance of unusual physical stresses is
advised. Increased flow and a shortening of the diastolic
filling period by tachycardia increase left atrial pressure
against an obstructed MV. Agents with negative chronotropic
properties, such as beta blockers or heart rate–regulating
calcium channel blockers, may be of benefit in patients in
sinus rhythm who have exertional symptoms if these symptoms occur with high heart rates.411,412 The greater efficacy of
a beta blocker compared with a heart rate–regulating calcium
channel blocker has been reported.413 Some patients with MS
have increased bronchial reactivity that may improve with
inhaled corticosteroids.414 Salt restriction and intermittent
administration of a diuretic are useful if there is evidence of
pulmonary vascular congestion. Digitalis does not benefit
patients with MS in sinus rhythm unless there is LV or RV
dysfunction.415
Although MS is a slowly progressive condition, acute
pulmonary edema can occur suddenly in asymptomatic patients with severe MS, especially with the onset of rapid atrial
fibrillation, and this can be rapidly fatal. Thus, patients should
be counseled to seek medical attention immediately if they
experience a sudden marked increase in shortness of breath.
3.4.3.2. Medical Therapy: Atrial Fibrillation
Patients with MS are prone to developing atrial arrhythmias,
particularly atrial fibrillation and atrial flutter. Thirty to forty
percent of patients with symptomatic MS develop atrial
fibrillation.367,368 Structural changes from the pressure and
volume overload alter the electrophysiological properties of
the left atrium,380 and the rheumatic process itself may lead to
fibrosis of the internodal and interatrial tracts and damage to
the sinoatrial node. There may be significant hemodynamic
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consequences resulting from the acute development of atrial
fibrillation, primarily from the rapid ventricular rate, which
shortens the diastolic filling period and causes elevation of
left atrial pressure. Atrial fibrillation occurs more commonly
in older patients367 and is associated with a poorer prognosis,
with a 10-year survival rate of 25% compared with 46% in
patients who remain in sinus rhythm.369 The risk of arterial
embolization, especially stroke, is significantly increased in
patients with atrial fibrillation.367,368,416 – 418
Treatment of an acute episode of rapid atrial fibrillation
consists of anticoagulation with heparin and control of the
heart rate response. Intravenous digoxin, heart rate–
regulating calcium channel blockers, or beta blockers should
be used to control ventricular response by slowing conduction
through the atrioventricular node. Intravenous or oral amiodarone can also be used when beta blockers or heart rateregulating calcium channel blockers cannot be used. If there
is hemodynamic instability, electrical cardioversion should be
undertaken urgently, with intravenous heparin before, during,
and after the procedure. In selected patients, chemical cardioversion may also be attempted. Patients who have been in
atrial fibrillation longer than 24 to 48 h without anticoagulation are at an increased risk for embolic events after cardioversion, but embolization may occur with less than 24 h of
atrial fibrillation. The decision to proceed with elective
cardioversion is dependent on multiple factors, including
duration of atrial fibrillation, hemodynamic response to the
onset of atrial fibrillation, a documented history of prior
episodes of atrial fibrillation, and a history of prior embolic
events. If the decision has been made to proceed with elective
cardioversion in a patient who has had documented atrial
fibrillation for longer than 24 to 48 h and who has not been on
long-term anticoagulation, 1 of 2 approaches is recommended
based on data from patients with nonrheumatic atrial fibrillation. The first is anticoagulation with warfarin for more than
3 weeks, followed by elective cardioversion.419 The second is
anticoagulation with heparin and transesophageal echocardiography to look for left atrial thrombus. In the absence of left
atrial thrombus, cardioversion is performed with intravenous
heparin before, during, and after the procedure.420 It is
important to continue long-term anticoagulation after
cardioversion.
Recurrent paroxysmal atrial fibrillation may be treated for
maintenance of sinus rhythm in selected patients with Class
IC antiarrhythmic drugs (in conjunction with negative dromotropic agent) or Class III antiarrhythmic drugs; however,
eventually, the atrial fibrillation becomes resistant to prevention or cardioversion,376 and control of ventricular response
becomes the mainstay of therapy. Digoxin slows the heart
rate response in patients with atrial fibrillation and MS.415
However, heart rate–regulating calcium channel blockers or
beta blockers are more effective for preventing exerciseinduced increases in heart rate. Patients with either paroxysmal or sustained atrial fibrillation should be treated with
long-term anticoagulation with warfarin to prevent embolic
events if they do not have a strong contraindication to
anticoagulation.417,421 It is controversial whether percutaneous mitral valvotomy should be performed in patients with
new-onset atrial fibrillation and moderate to severe MS who
are otherwise asymptomatic.
Successful percutaneous balloon mitral commissurotomy
may not prevent the development of atrial fibrillation. Advanced age and left atrial dimension appear to be the
important predictors of development of atrial fibrillation.422
3.4.3.3. Medical Therapy: Prevention of Systemic
Embolization
Class I
1. Anticoagulation is indicated in patients with MS and
atrial fibrillation (paroxysmal, persistent, or permanent). (Level of Evidence: B)
2. Anticoagulation is indicated in patients with MS and a
prior embolic event, even in sinus rhythm. (Level of
Evidence: B)
3. Anticoagulation is indicated in patients with MS with
left atrial thrombus. (Level of Evidence: B)
Class IIb
1. Anticoagulation may be considered for asymptomatic
patients with severe MS and left atrial dimension
greater than or equal to 55 mm by echocardiography.*
(Level of Evidence: B)
2. Anticoagulation may be considered for patients with
severe MS, an enlarged left atrium, and spontaneous
contrast on echocardiography. (Level of Evidence: C)
Systemic embolization may occur in 10% to 20% of patients
with MS.367,368,416 The risk of embolization is related to age
and the presence of atrial fibrillation.367,368,416 – 418 One third of
embolic events occur within 1 month of the onset of atrial
fibrillation, and two thirds occur within 1 year. The frequency
of embolic events does not seem to be related to the severity
of MS, cardiac output, size of the left atrium, or even the
presence or absence of heart failure symptoms.368,417,424 An
embolic event may thus be the initial manifestation of MS.367
In patients who have experienced an embolic event, the
frequency of recurrence is as high as 15 to 40 events per 100
patient-months.417– 421
There are no randomized trials examining the efficacy of
anticoagulation in preventing embolic events specifically in
patients with MS. Retrospective studies have shown a 4- to
15-fold decrease in the incidence of embolic events with
anticoagulation in these patients.417,421 This benefit applies to
both systemic and pulmonary embolism. Most trials involved
patients who had 1 embolus before the onset of anticoagulation
therapy.421 However, large randomized trials have demonstrated
a significant reduction in embolic events by treatment with
anticoagulation in subsets of patients with atrial fibrillation not
associated with MS.425,426 In these randomized trials, the subset
of patients who benefited most from anticoagulation were those
with the highest risk of embolic events.353,354 Patients with MS
at the highest risk for future embolic events are those with prior
embolic events and those with paroxysmal or persistent atrial
*This recommendation is based on a grade C level of evidence given by
the American College of Chest Physicians Fourth Consensus Conference
on Antithrombotic Therapy.423
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fibrillation.367,368,416 – 418,421 Paroxysmal atrial fibrillation may be
difficult to detect; ambulatory ECG monitoring is valuable in
patients with palpitations. There are no data to support the
concept that oral anticoagulation is beneficial in patients with
MS who have not had atrial fibrillation or an embolic event. It is
controversial whether patients without atrial fibrillation or an
embolic event who might be at higher risk for future embolic
events (i.e., those with severe MS or an enlarged left atrium)
should be considered for long-term warfarin therapy.423,427
Although embolic events are thought to originate from left
atrial thrombi,417,418 the presence or absence of a left atrial
thrombus does not appear to correlate with embolic
events.367,418 Left atrial thrombi are found during surgery in
15% to 20% of patients with prior embolic events and a
similar number of patients without embolic events.367,416
However, in clinical practice, anticoagulation is frequently
used if obvious left atrial thrombi are detected.
It has been suggested that surgical commissurotomy reduces the incidence of future embolic events.381 There are no
randomized trial data to support this hypothesis, and the
retrospective studies that have been reported were performed
before the availability of standardized anticoagulation regimens. Other retrospective studies have concluded that surgery
does not decrease the incidence of systemic emboli.380,428,429
One prospective study has reported decreased risk for arterial
embolism after mitral commissurotomy.430
3.4.4. Recommendations Regarding Physical Activity and
Exercise
Many patients with mild MS will remain asymptomatic even
with strenuous exercise. In more severe MS, exercise can
cause sudden marked increases in pulmonary venous pressure
from the increase in heart rate and cardiac output, at times
resulting in pulmonary edema.375,376 The long-term effects of
repeated exertion-related increases in pulmonary venous and
pulmonary artery pressures on the lung or right ventricle remain
unknown. MS rarely causes sudden death.367–369 These factors
must be considered when recommending physical activity and
exercise for the patient with MS.
In the majority of patients with MS, recommendations for
exercise are symptom limited. Patients should be encouraged
to pursue a low-level aerobic exercise program for maintenance of cardiovascular fitness. Exertional symptoms of
dyspnea are the limiting factors in terms of exercise tolerance.
However, there is a subset of asymptomatic patients who wish to
participate in competitive athletics who may deny symptoms.
The 36th Bethesda Conference on Recommendations for Determining Eligibility for Competition in Athletes with Cardiovascular Abnormalities published guidelines for patients with MS
who wish to engage in competitive athletics.138
3.4.5. Serial Testing
Serial follow-up testing of a patient with MS should be based
on whether the results of a test will dictate either a change in
therapy or a recommendation for a procedure. Patients with
MS usually have years without symptoms before the onset of
deterioration.367,380 All patients should be informed that any
change in symptoms warrants re-evaluation. In the asymptomatic patient, yearly re-evaluation is recommended (Fig. 5).
At the time of the yearly evaluation, a history, physical
e565
examination, chest X-ray, and ECG should be obtained.
Physical examination is useful to assess the progression of the
severity of MS. A shortening of the A2-OS interval, longer
duration of the middiastolic murmur, and the presence of
findings of pulmonary hypertension indicates more severe
MS. An echocardiogram is not recommended yearly unless
there is a change in clinical status or the patient has severe
MS. Ambulatory ECG monitoring (Holter or event recorder)
to detect paroxysmal atrial fibrillation is indicated in patients
with palpitations.
3.4.6. Evaluation of the Symptomatic Patient
Patients who develop symptoms should undergo evaluation
with a history, physical examination, ECG, chest X-ray, and
echocardiogram (Figs. 6 and 7). Two-dimensional and Doppler echocardiography are indicated to evaluate MV morphology, MV hemodynamics, and pulmonary artery pressure.
Patients with NYHA functional class II symptoms and
moderate or severe MS (MV area less than or equal to 1.5
cm2 or mean gradient greater than 5 mm Hg) may be
considered for mitral balloon valvotomy if they have suitable
MV morphology and no left atrial thrombi. Patients who have
NYHA functional class III or IV symptoms and evidence of
severe MS have a poor prognosis if left untreated367–369 and
should be considered for intervention with either balloon
valvotomy or surgery.
A subset of patients have significant limiting symptoms,
yet clinical and Doppler echocardiographic evaluation do not
indicate moderate or severe MS. In such patients, formal
exercise testing or dobutamine stress may be useful to
differentiate symptoms due to MS from other causes of
symptoms. Exercise tolerance, heart rate and blood pressure
response, transmitral gradient, and pulmonary artery pressure
can be obtained at rest and during exercise. This can usually
be accomplished with either supine bicycle or upright exercise testing with Doppler recording of TR and transmitral
velocities.406 – 409 Right- and left-heart catheterization with
exercise may be helpful and occasionally necessary.431 Patients who are symptomatic with a significant elevation of
pulmonary artery pressure (greater than 60 mm Hg), mean
transmitral gradient (greater than 15 mm Hg), or pulmonary
artery wedge pressure (greater than 25 mm Hg) during
exercise375,407– 409,432,433 have hemodynamically significant MS
and should be considered for further intervention. Alternatively,
patients who do not manifest elevation in either pulmonary
artery, pulmonary artery wedge, or transmitral pressures coincident with development of exertional symptoms most likely
would not benefit from intervention on the MV.
3.4.7. Indications for Invasive Hemodynamic Evaluation
Class I
1. Cardiac catheterization for hemodynamic evaluation
should be performed for assessment of severity of MS
when noninvasive tests are inconclusive or when there is
discrepancy between noninvasive tests and clinical findings regarding severity of MS. (Level of Evidence: C)
2. Catheterization for hemodynamic evaluation including
left ventriculography (to evaluate severity of MR) for
patients with MS is indicated when there is a discrep-
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Circulation
October 7, 2008
Figure 6. Management strategy for patients with mitral stenosis and mild symptoms.
*The committee recognizes that there may be variability in the measurement of mitral valve area (MVA) and that the mean transmitral gradient, pulmonary artery wedge
pressure (PAWP), and pulmonary artery systolic pressure (PP) should also be taken into consideration. †There is controversy as to whether patients with severe mitral stenosis (MVA less than 1.0 cm2) and severe pulmonary hypertension (PH; PP greater than 60 to 80 mm Hg) should undergo percutaneous mitral balloon valvotomy (PMBV)
or mitral valve replacement to prevent right ventricular failure. CXR indicates chest X-ray; ECG, electrocardiogram; echo, echocardiography; LA, left atrial; MR, mitral regurgitation; MVG, mean mitral valve pressure gradient; NYHA, New York Heart Association; PAP, pulmonary artery pressure; and 2D, 2-dimensional.
ancy between the Doppler-derived mean gradient and
valve area. (Level of Evidence: C)
Class IIa
1. Cardiac catheterization is reasonable to assess the
hemodynamic response of pulmonary artery and left
atrial pressures to exercise when clinical symptoms
and resting hemodynamics are discordant. (Level of
Evidence: C)
2. Cardiac catheterization is reasonable in patients with
MS to assess the cause of severe pulmonary arterial
hypertension when out of proportion to severity of
MS as determined by noninvasive testing. (Level of
Evidence: C)
Class III
1. Diagnostic cardiac catheterization is not recommended
to assess the MV hemodynamics when 2D and Doppler
echocardiographic data are concordant with clinical
findings. (Level of Evidence: C)
Hemodynamic measurements by cardiac catheterization can
be used to determine the severity of MS. Direct measure-
ments of left atrial and LV pressure determine the transmitral
gradient, which is the fundamental expression of severity of
MS.372 Because the severity of obstruction is dependent on
both flow and gradient,376 the hydraulic Gorlin equation has
been used in the catheterization laboratory to derive a
calculated valve area.139 Pulmonary artery pressure and pulmonary vascular resistance can be measured to determine the
effect of MS on the pulmonary circulation.
With the advent of Doppler echocardiography, cardiac
catheterization is no longer required for assessment of hemodynamics in the majority of patients with isolated MS.
Reliable measurements of the transmitral gradient may be
obtained with the modified Bernoulli equation.389,391 The
potential problems of angle dependence, pressure recovery,
proximal acceleration, and inadequate velocity signals that
occur in the evaluation of other valve lesions are not present
with MS. There is often overestimation of the transmitral
gradient when catheterization is performed with pulmonary
artery wedge pressure as a substitute for left atrial pressure,
even after correction for phase delay. Thus, the transmitral
gradient derived by Doppler echocardiography may be more
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e567
Figure 7. Management strategy for patients with mitral stenosis and moderate to severe symptoms.
*The writing committee recognizes that there may be variability in the measurement of mitral valve area (MVA) and that the mean transmitral gradient, pulmonary artery
wedge pressure (PAWP), and pulmonary artery systolic pressure (PP) should also be taken into consideration. †It is controversial as to which patients with less favorable
valve morphology should undergo percutaneous mitral balloon valvotomy (PMBV) rather than mitral valve surgery (see text). CXR, chest X-ray; ECG, electrocardiography;
echo, echocardiography; LA, left atrial; MR, mitral regurgitation; MVG, mean mitral valve pressure gradient; MVR, mitral valve replacement; NYHA, New York Heart Association; and 2D, 2-dimensional.
accurate than that obtained by cardiac catheterization with
pulmonary artery wedge pressure.434
MV area is derived from either the half-time method or the
continuity equation by Doppler echocardiography. These
measurements correlate well in most instances with valve
areas from cardiac catheterization.401,402 The Doppler halftime method may be inaccurate if there are changes in
compliance of the left atrium or left ventricle,402,403 especially
after mitral balloon valvotomy, or if there is concomitant AR.
There are limitations to MV area calculations derived from
catheter hemodynamic measurements, because the Gorlin
equation may not be valid under varying hemodynamic
conditions, and the empirical coefficient of discharge may be
inaccurate with different orifice shapes.379,404 Calculation of
valve area by catheterization is also dependent on measurement of transmitral gradient and cardiac output. Gradients
may be inaccurate when pulmonary artery wedge pressure is
used, as may cardiac output derived by the thermodilution
method. When there is concomitant MR, measures of forward
flow by thermodilution or the Fick method will result in
underestimation of the MV area, as discussed in Section
3.7.2.2.2. Thus, there may be inaccuracies with both Doppler
and catheter-derived valve areas, and a single valve area
should not be the sole measure of MS severity. Estimates of
the severity of MS should be based on all data, including
transmitral gradient, MV area, pulmonary artery wedge pressure, and pulmonary artery pressure.
In most instances, Doppler measurements of transmitral
gradient, valve area, and pulmonary pressure will correlate
well with each other. Catheterization is indicated to assess
hemodynamics when there is a discrepancy between Dopplerderived hemodynamics and the clinical status of a symptomatic patient. Absolute left- and right-side pressure measurements should be obtained by catheterization when there is
elevation of pulmonary artery pressure out of proportion to
mean gradient and valve area. Invasive hemodynamic evalu-
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Circulation
October 7, 2008
ation is also necessary to assess the severity and the hemodynamic cause of increased pulmonary vascular resistance,
because pulmonary vasodilator therapy may be of benefit in
such patients. Catheterization including left ventriculography
(to evaluate the severity of MR) is indicated when there is a
discrepancy between the Doppler-derived mean gradient and
valve area. Aortic root angiography may be necessary to
evaluate severity of AR. If symptoms appear to be out of
proportion to noninvasive assessment of resting hemodynamics, right- and left-heart catheterization with exercise may be
useful. Transseptal catheterization may rarely be required for
direct measurement of left atrial pressure if there is doubt
about the accuracy of pulmonary artery wedge pressure.
Coronary angiography may be required in selected patients
who may need intervention (see Section 10.2.).
3.4.8. Indications for Percutaneous Mitral Balloon
Valvotomy
Class I
1. Percutaneous mitral balloon valvotomy is effective for
symptomatic patients (NYHA functional class II, III,
or IV), with moderate or severe MS* and valve morphology favorable for percutaneous mitral balloon
valvotomy in the absence of left atrial thrombus or
moderate to severe MR. (Level of Evidence: A)
2. Percutaneous mitral balloon valvotomy is effective for
asymptomatic patients with moderate or severe MS*
and valve morphology that is favorable for percutaneous mitral balloon valvotomy who have pulmonary
hypertension (pulmonary artery systolic pressure
greater than 50 mm Hg at rest or greater than 60 mm
Hg with exercise) in the absence of left atrial thrombus
or moderate to severe MR. (Level of Evidence: C)
Class IIa
1. Percutaneous mitral balloon valvotomy is reasonable
for patients with moderate or severe MS* who have a
nonpliable calcified valve, are in NYHA functional
class III–IV, and are either not candidates for surgery
or are at high risk for surgery. (Level of Evidence: C)
Class IIb
1. Percutaneous mitral balloon valvotomy may be considered for asymptomatic patients with moderate or
severe MS* and valve morphology favorable for percutaneous mitral balloon valvotomy who have new
onset of atrial fibrillation in the absence of left atrial
thrombus or moderate to severe MR. (Level of
Evidence: C)
2. Percutaneous mitral balloon valvotomy may be considered for symptomatic patients (NYHA functional class
II, III, or IV) with MV area greater than 1.5 cm2 if
there is evidence of hemodynamically significant MS
based on pulmonary artery systolic pressure greater
than 60 mm Hg, pulmonary artery wedge pressure of
25 mm Hg or more, or mean MV gradient greater than
15 mm Hg during exercise. (Level of Evidence: C)
*See Table 4.27
3. Percutaneous mitral balloon valvotomy may be considered as an alternative to surgery for patients with
moderate or severe MS who have a nonpliable calcified
valve and are in NYHA functional class III–IV. (Level
of Evidence: C)
Class III
1. Percutaneous mitral balloon valvotomy is not indicated
for patients with mild MS. (Level of Evidence: C)
2. Percutaneous mitral balloon valvotomy should not be
performed in patients with moderate to severe MR or
left atrial thrombus. (Level of Evidence: C)
The concept of mitral commissurotomy was first proposed by
Brunton in 1902, and the first successful surgical mitral
commissurotomy was performed in the 1920s. By the late
1940s and 1950s, both transatrial and transventricular closed
surgical commissurotomy were accepted clinical procedures.
With the development of cardiopulmonary bypass, open
mitral commissurotomy and replacement of the MV became
the surgical procedures of choice for the treatment of MS.
Percutaneous mitral balloon valvotomy emerged in the mid
1980s. This procedure, in which 1 or more large balloons is
inflated across the MV by a catheter-based approach, has
become the preferred procedure in selected patients compared
with surgical approaches.
The mechanism of improvement from surgical commissurotomy or percutaneous valvotomy is related to the successful
opening of commissures that were fused by the rheumatic
process. This results in a decrease in gradient and an increase
in the calculated MV area, with resulting improvement in
clinical symptomatology. The extent of hemodynamic and
clinical improvement is dependent on the magnitude of
decrease of transmitral gradient and increase in valve area.
Patients with pliable, noncalcified valves and minimal fusion
of the subvalvular apparatus achieve the best immediate and
long-term results when a substantial increase in the valve area
can be achieved.
Closed surgical commissurotomy with either a transatrial
or transventricular approach was popularized in the 1950s
and 1960s. Early and long-term postoperative follow-up
studies showed that patients had a significant improvement in
symptoms and survival compared with those treated medically.435– 437 Closed commissurotomy remains the surgical technique of choice in many developing countries, but open
commissurotomy is the accepted surgical procedure in most
institutions in the United States,438 – 441 because it allows
direct inspection of the MV apparatus and, under direct
vision, division of the commissures, splitting of fused chordae tendineae and papillary muscles, and debridement of
calcium deposits. Amputation of the left atrial appendage is
recommended to reduce the likelihood of postoperative
thromboembolic events.442 The results of the operation are
dependent on the morphology of the MV apparatus and the
surgeon’s skill and experience. In patients with marked
deformity of the MV apparatus, a decision for MV replacement can be made at the time of operation. The risk of surgery
is between 1% and 3%, depending on the concomitant
medical status of the patient.439 – 441 Although there is an
inherent bias in the large reported surgical series, the 5-year
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Bonow et al
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
reoperation rate is 4% to 7%, and the 5-year complicationfree survival rate ranges from 80% to 90%.
Percutaneous mitral balloon valvotomy was first performed
in the early 1980s and became a clinically approved technique in 1994. In the past decade, there have been major
advances in techniques and equipment, as well as changes in
patient selection. A double-balloon technique was the initial
procedure used by most investigators. Today, an hourglassshaped single balloon (Inoue balloon) is used by most centers
performing the technique. Percutaneous mechanical mitral
commissurotomy with a metallic valvotome has been introduced, and the results appear to be similar. The advantage of
this technique is that multiple uses of the metallic device after
sterilization are feasible and reduce the cost of treatment443;
however, it is not widely available, and there is limited
experience with this technique. The balloon valvotomy procedure itself is technically challenging and involves a steep
learning curve. There is a higher success rate and lower
complication rate in experienced, high-volume centers.444
Thus, the results of the procedure are highly dependent on the
experience of the operators involved, which must be considered when making recommendations for proceeding with this
technique.
The immediate results of percutaneous mitral valvotomy are
similar to those of mitral commissurotomy.444 – 453 The mean
valve area usually doubles (from 1.0 to 2.0 cm2), with a 50% to
60% reduction in transmitral gradient. Overall, 80% to 95% of
patients may have a successful procedure, which is defined as a
MV area greater than 1.5 cm2 and a decrease in left atrial
pressure to less than 18 mm Hg in the absence of complications.
The most common acute complications reported in large series
include severe MR, which occurs in 2% to 10%, and a residual
atrial septal defect. A large atrial septal defect (greater than 1.5:1
left-to-right shunt) occurs in fewer than 12% of patients with the
double-balloon technique and fewer than 5% with the Inoue
balloon technique. Smaller atrial septal defects may be detected
by transesophageal echocardiography in larger numbers of
patients. Less frequent complications include perforation of the
left ventricle (0.5% to 4.0%), embolic events (0.5% to 3%), and
myocardial infarction (0.3% to 0.5%). The mortality rate with
balloon valvotomy in larger series has ranged from 1% to
2%444 – 447,453; however, with increasing experience with the
procedure, percutaneous mitral valvotomy can be done in
selected patients with a mortality rate of less than 1%.448
Simultaneous echocardiography may be useful in directing
balloon placement and assessing hemodynamics.
Follow-up information after percutaneous balloon valvotomy is limited. Event-free survival (freedom from death,
repeat valvotomy, or MV replacement) overall is 50% to 65%
over 3 to 7 years, with an event-free survival of 80% to 90% in
patients with favorable MV morphology.398,446,448 – 455 More than
90% of patients free of events remain in NYHA functional class
I or II after percutaneous mitral valvotomy. Randomized trials
have compared percutaneous balloon valvotomy with both
closed and open surgical commissurotomy.456 – 461 These trials,
summarized in Table 18, consisted primarily of younger patients
(aged 10 to 30 years) with pliable MV leaflets. There was no
significant difference in acute hemodynamic results or complication rate between percutaneous mitral valvotomy and surgery,
e569
and early follow-up data indicate no difference in hemodynamics, clinical improvement, or exercise time. However, longerterm follow-up studies at 3 to 7 years459,460 indicate more
favorable hemodynamic and symptomatic results with percutaneous balloon valvotomy than with closed commissurotomy. Of
the 2 studies that compared percutaneous balloon valvotomy
with open commissurotomy, one reported equivalent results,460
and the other showed more favorable results with open commissurotomy.461 This latter study included older patients with higher
MV scores.
The immediate results, acute complications, and follow-up
results of percutaneous balloon valvotomy are dependent on
multiple factors. It is of utmost importance that this procedure
be performed in centers with skilled and experienced operators.
Other factors include age, NYHA functional class, stenosis
severity, LV end-diastolic pressure, cardiac output, and pulmonary artery wedge pressure.446,448,449,453 The underlying MV
morphology is the factor of greatest importance in determining
outcome,394 – 400,446,449,450,453,454,462 and immediate postvalvotomy
hemodynamics are predictive of long-term clinical outcome.448,450,453 Patients with valvular calcification, thickened
fibrotic leaflets with decreased mobility, and subvalvular fusion
have a higher incidence of acute complications and a higher rate
of recurrent stenosis on follow-up (Table 19). Because the
success of the procedure is dependent on the ability to split fused
commissures, the presence of marked fusion and severe calcification of commissures is associated with an increased complication rate and higher incidence of recurrent symptoms.396 –398
Alternatively, in patients with noncalcified pliable valves, mild
subvalvular fusion, and no calcium in the commissures, the
procedure can be performed with a high success rate (greater
than 90%), low complication rate (less than 3%), and sustained
improvement in 80% to 90% over a 3- to 7-year follow-up
period.397,398,400,446,448,450,453,454
Relative contraindications to percutaneous balloon valvotomy include the presence of a left atrial thrombus and
significant (3⫹ to 4⫹) MR. Transesophageal echocardiography is recommended before the procedure to determine the
presence of left atrial thrombus, specifically examining the
left atrial appendage. If a thrombus is found, 3 months of
anticoagulation with warfarin may result in resolution of the
thrombus. A prognostic model for predicting the resolution of
left atrial thrombi in candidates for percutaneous mitral
commissurotomy has been suggested. Combined clinical
functional class and echocardiographic left atrial thrombus
are predictive of the outcome of oral anticoagulation for
thrombus resolution.463
In centers with skilled, experienced operators, percutaneous balloon valvotomy should be considered the initial
procedure of choice for symptomatic patients with moderate
to severe MS who have a favorable valve morphology in the
absence of significant MR or left atrial thrombus. Echocardiographic parameters that can predict the risks of developing
severe MR after percutaneous mitral valvotomy by the Inoue
technique have been reported,464 and the overall echocardiographic assessment397,398,400 identifies patients with less favorable long-term outcome (Tables 17 and 19). In asymptomatic patients with a favorable valve morphology,
percutaneous mitral valvotomy may be considered if there is
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A dash indicates that data were not available. *Significant difference (p less than 0.05) in increased mitral valve area by percutaneous mitral balloon valvotomy (PMBV) compared with surgical commissurotomy.
CC indicates closed commissurotomy; FC, functional class; NYHA, New York Heart Association; OC, open commissurotomy; Post, postprocedure; and Pre, preprocedure.
84
96
18
2.3 ⫾ 0.3
1.0 ⫾ 0.2
—
8.2
49 ⫾ 10
OC
50 mo
82
PMBV
Cotrufo et al., 1999461
38 mo
111
7.6
—
33
67
88
28
1.8 ⫾ 0.3
1.0 ⫾ 0.2
—
90
47 ⫾ 14
—
50
93
—
—
1.3 ⫾ 0.3
1.8 ⫾ 0.3
0.9 ⫾ 0.2
0.9 ⫾ 0.2
—
—
6.0
—
6.0
28 ⫾ 10
30
CC
27 ⫾ 9
30
OC
6.0
30
Ben Farhat et al., 1998460
7y
PMBV
29 ⫾ 12
—
57
87
90
—
1.8 ⫾ 0.4
0.9 ⫾ 0.2
—
72
30
CC
7.0
—
—
13
1.8 ⫾ 0.4
0.9 ⫾ 0.3
—
—
31 ⫾ 9
—
—
10
2.4 ⫾ 0.4*
0.9 ⫾ 0.3
—
6.7
30 ⫾ 9
30
Reyes et al., 1994459
3y
PMBV
—
—
—
—
—
4
5
2.3 ⫾ 0.1
2.1 ⫾ 0.4
0.8 ⫾ 0.2
0.8 ⫾ 0.3
—
—
—
—
20 ⫾ 6
100
19 ⫾ 5
100
CC
Arora et al., 1993
458
22 mo
PMBV
8.4
—
—
—
—
—
—
—
1.7 ⫾ 0.2
1.6 ⫾ 0.2
0.8 ⫾ 2
0.9 ⫾ 0.4
12 ⫾ 2
10 ⫾ 2
7.2
20
28 ⫾ 1
20
CC
7 mo
Turi et al., 1991457
23
22
PMBV
CC
Immediate
Patel et al., 1991456
Procedure
Author, Year
PMBV
27 ⫾ 8
20 ⫾ 6
91
6.0
18 ⫾ 4
—
—
—
—
1.3 ⫾ 0.3
2.1 ⫾ 0.7*
0.8 ⫾ 0.3
0.7 ⫾ 0.2
6⫾3
4⫾3
6.0
30 ⫾ 11
26 ⫾ 26
12 ⫾ 5
Post
Pre
Post
Pre
Age, y
12 ⫾ 4
Freedom From
Reintervention
(%)
Restenosis
(%)
Mitral Valve Area
Mitral Gradient
October 7, 2008
Average
Score
No. of
Patients
Mean
Follow-Up
Randomized Trials of Percutaneous Mitral Balloon Valvotomy and Surgical Commissurotomy
Table 18.
—
Circulation
NYHA
FC I (%)
e570
evidence of a hemodynamic effect on left atrial pressure or
pulmonary circulation (pulmonary artery systolic pressure
greater than 50 mm Hg at rest or greater than 60 mm Hg with
exercise); the strength of evidence for this recommendation is
low because there are no data comparing the results of
percutaneous balloon valvotomy and those of medical therapy in such asymptomatic patients. It is controversial whether
severely symptomatic patients with less favorable valve
morphology should undergo this catheter-based procedure465
(Fig. 7; Table 19). Although there is a higher acute complication rate and a lower event-free survival rate (approximately 50% at 5 years in these patients compared with 80%
to 90% in patients with favorable valve morphology), this
must be weighed against the average in-hospital mortality of
surgical MV replacement of 6%,164,165 which is as high as
16% in low-volume centers,166 and the expected long-term
outcome. In many cases, MV replacement is preferable for
patients with severe valvular calcification and deformity.
Patients who are being considered for an intervention should
undergo evaluation with a history, physical examination, and 2D
and Doppler echocardiographic examination. The appearance
and mobility of the MV apparatus and commissures should be
evaluated by 2D echocardiography, and the transmitral gradient,
MV area, and pulmonary artery pressure should be obtained
from the Doppler examination. If there is a discrepancy between
symptoms and hemodynamics, a formal hemodynamic exercise
test may be performed. Patients thought to be candidates for
percutaneous mitral valvotomy should undergo transesophageal
echocardiography to rule out left atrial thrombus and to examine
the severity of MR. If a left atrial thrombus is present, a repeat
transesophageal echocardiogram can be performed after several
months of anticoagulation. Percutaneous mitral balloon valvotomy may be safely performed if there has been resolution of the
thrombus. If there is a suspicion that the severity of MR is 3⫹ or
4⫹ based on the physical examination or echocardiogram, a left
ventriculogram should be performed. Mitral balloon valvotomy
should not be performed in patients who have grade 3⫹ or 4⫹
MR. Percutaneous mitral balloon valvotomy should be performed only by skilled operators at institutions with extensive
experience in performing the technique.444,447 Thus, the decision
to proceed with percutaneous balloon valvotomy or surgical
commissurotomy is dependent on the experience of the operator
and institution. Because of the less invasive nature of percutaneous balloon valvotomy compared with surgical intervention,
appropriate patients without symptoms or those with NYHA
functional class II symptoms may be considered for catheterbased therapy (Figs. 5 and 6).
3.4.9. Indications for Surgery for Mitral Stenosis
Class I
1. MV surgery (repair if possible) is indicated in patients
with symptomatic (NYHA functional class III–IV)
moderate or severe MS* when 1) percutaneous mitral
balloon valvotomy is unavailable, 2) percutaneous mitral balloon valvotomy is contraindicated because of
left atrial thrombus despite anticoagulation or because
*See Table 4.27
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Table 19.
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
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Echocardiographic Prediction of Outcome of Percutaneous Mitral Balloon Valvotomy
Author, Year
Mean
FollowUp, mo
Cohen et al., 1992446
36 ⫾ 20
Palacios et al., 1995454
20 ⫾ 12
Dean et al., 1996449
38 ⫾ 16
Echo Criteria
No. of
Patients
Age, y
Survival
Survival Free
of Events
84
—
—
68% at 5 y
Score less than or
equal to 8
Score greater than 8
Iung et al., 1996397
32 ⫾ 18
Cannan et al., 1997398
22 ⫾ 10
Palacios et al., 2002453
50 ⫾ 44
52
—
—
28% at 5 y
Score less than or
equal to 8
211
48⫾14
98% at 4 y
98% at 4 y
Score greater than 8
116
64 ⫾ 11
39% at 4 y
39% at 4 y
Score less than or
equal to 8
272
49 ⫾ 13
95% at 4 y
—
Score 8 to 12
306
58 ⫾ 15
83% at 4 y
—
Score greater than 12
24
58 ⫾ 15
24% at 4 y
—
Group 1
87
—
89% at 3 y
—
78% at 3 y
—
65% at 3 y
—
86% at 3 y
Group 2
311
Group 3
130
Com Ca⫺
120
Com Ca⫹
Score greater than 8
Score less than 8
46 ⫾ 13
—
29
—
—
40% at 3 y
278
63 ⫾ 14
82% at 12 y
38% at 12 y
601
51 ⫾ 14
57% at 12 y
22% at 12 y
Events
Death, MVR, repeat
PMBV
Death, MVR, NYHA FC
III–IV symptoms
Death
Death, MVR, repeat
PMBV, FC III–IV
symptoms
Death, MVR, repeat
PMBV
Death, MVR, repeat
PMBV
Echocardiography score based on scoring system of Wilkins et al. ; echocardiographic group based on valve flexibility, chordal fusion, and valve calcification in
Iung et al.397
Com Ca indicates commissural calcification; echo, echocardiographic; FC, functional class; MVR, mitral valve replacement; NYHA, New York Heart Association; and
PMBV, percutaneous mitral balloon valvotomy.
400
concomitant moderate to severe MR is present, or 3)
the valve morphology is not favorable for percutaneous
mitral balloon valvotomy in a patient with acceptable
operative risk. (Level of Evidence: B)
2. Symptomatic patients with moderate to severe MS*
who also have moderate to severe MR should receive
MV replacement, unless valve repair is possible at the
time of surgery. (Level of Evidence: C)
Class IIa
1. MV replacement is reasonable for patients with severe
MS* and severe pulmonary hypertension (pulmonary
artery systolic pressure greater than 60 mm Hg) with
NYHA functional class I–II symptoms who are not
considered candidates for percutaneous mitral balloon
valvotomy or surgical MV repair. (Level of Evidence:
C)
Class IIb
1. MV repair may be considered for asymptomatic patients with moderate or severe MS* who have had
recurrent embolic events while receiving adequate
anticoagulation and who have valve morphology favorable for repair. (Level of Evidence: C)
Class III
1. MV repair for MS is not indicated for patients with
mild MS. (Level of Evidence: C)
2. Closed commissurotomy should not be performed in
patients undergoing MV repair; open commissurotomy is the preferred approach. (Level of Evidence: C)
MV replacement is an accepted surgical procedure for patients with severe MS who are not candidates for surgical
commissurotomy or percutaneous mitral valvotomy. The
perioperative mortality of MV replacement is dependent on
multiple factors, including functional status, age, LV function, cardiac output, concomitant medical problems, and
concomitant CAD. In the young, healthy person, MV replacement can be performed with a risk of less than 5%; however,
in the older patient with concomitant medical problems or
pulmonary hypertension at systemic levels, the perioperative
mortality of MV replacement may be as high as 10% to
20%.166,167 MV replacement with preservation of subvalvular
apparatus aids in maintaining LV function,466 but this can be
particularly difficult in patients with rheumatic MS. Alternative approaches to ventricular preservation exist, such as
artificial chordal reconstruction before MV replacement.467,468 Complications of MV replacement include valve
thrombosis, valve dehiscence, valve infection, valve malfunction, and embolic events. These are discussed in Section 7.3.
There is also the known risk of long-term anticoagulation in
patients receiving mechanical prostheses.
If there is significant calcification, fibrosis, and subvalvular
fusion of the MV apparatus, commissurotomy or percutaneous balloon valvotomy is less likely to be successful, and MV
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replacement will be necessary. Given the risk of MV replacement and the potential long-term complications of a prosthetic valve, there are stricter indications for MV operation in
these patients with calcified fibrotic valves. In the patient with
NYHA functional class III symptoms due to severe MS or
combined MS/MR, MV replacement results in excellent
symptomatic improvement. Postponement of surgery until the
patient reaches the functional class IV symptomatic state
should be avoided, because operative mortality is high and
the long-term outcome is suboptimal. However, if the patient
presents in NYHA functional class IV heart failure, surgery
should not be denied, because the outlook without surgical
intervention is grave. It is controversial whether asymptomatic or mildly symptomatic patients with severe MS (valve
area less than 1 cm2) and severe pulmonary hypertension
(pulmonary artery systolic pressure greater than 60 to 80 mm
Hg) should undergo MV replacement to prevent RV failure,
but surgery is generally recommended in such patients. It is
recognized that patients with such severe pulmonary hypertension are rarely asymptomatic.
3.4.10. Management of Patients After Valvotomy or Commissurotomy
Symptomatic improvement occurs almost immediately after
successful percutaneous balloon valvotomy or surgical commissurotomy, although objective measurement of maximum
oxygen consumption may continue to improve over several
months postoperatively owing to slowly progressive improvement in skeletal muscle metabolism.469 Hemodynamic
measurements before and after either percutaneous valvotomy or surgical commissurotomy have confirmed a decrease
in left atrial pressure, pulmonary artery pressure, and pulmonary arteriolar resistance and an improvement in cardiac
output.470 – 473 In patients with significant right heart failure
after catheter-based or surgical relief of MV obstruction, inhaled
nitric oxide, intravenous prostacyclin, or an endothelin antagonist may be useful in reducing pulmonary vascular resistance
and pulmonary hypertension.474 Gradual regression of pulmonary hypertension over months has been demonstrated.470 – 472
Recurrent symptoms after successful surgical commissurotomy have been reported to occur in as many as 60% of
patients after 9 years405,435,475; however, recurrent stenosis
accounts for symptoms in fewer than 20% of patients.475 In
patients with an adequate initial result, progressive MR and
development of other valvular or coronary problems are more
frequently responsible for recurrent symptoms.475 Thus, in
patients presenting with symptoms late after commissurotomy, a comprehensive evaluation is required to look for other
causes. Patients undergoing percutaneous mitral valvotomy
with an unfavorable MV morphology have a higher incidence
of recurrent symptoms at 1- to 2-year follow-up due to either
an initial inadequate result or restenosis.476
The management of patients after successful percutaneous
balloon valvotomy or surgical commissurotomy is similar to
that of the asymptomatic patient with MS. A baseline echocardiogram should be performed after the procedure to obtain
a baseline measurement of postoperative hemodynamics and
to exclude significant complications such as MR, LV dysfunction, or atrial septal defect (in the case of percutaneous
valvotomy). This echocardiogram should be performed at
least 72 h after the procedure, because acute changes in atrial
and ventricular compliance immediately after the procedure
affect the reliability of the half-time in calculation of valve
area.402,403 Patients with severe MR or a large atrial septal
defect should be considered for early surgery; however, the
majority of small left-to-right shunts at the atrial level will
close spontaneously over the course of 6 months. In patients
with a history of atrial fibrillation, warfarin should be restarted 1 to 2 days after the procedure.
A history, physical examination, chest X-ray, and ECG
should be obtained at yearly intervals in the patient who
remains asymptomatic or minimally symptomatic. Prophylaxis against infective endocarditis (Section 2.3.1) and recurrence of rheumatic fever (Section 2.3.2.3; Table 1145 should
be followed. If the patient is in atrial fibrillation or has a
history of atrial fibrillation, anticoagulation is recommended,
as would be the case for all patients with MS. With recurrent
symptoms, extensive 2D and Doppler echocardiography
should be performed to evaluate the MV hemodynamics and
pulmonary artery pressure and to rule out significant MR or a
left-to-right shunt. As with all patients with MS, exercise
hemodynamics may be indicated in the patient with a discrepancy in clinical and hemodynamic findings.
Repeat percutaneous balloon valvotomy can be performed
in the patient in whom there is restenosis after either a prior
surgical commissurotomy or a balloon valvotomy.378,477 The
results of these procedures are adequate in many patients but
may be less satisfactory than the overall results of initial
valvotomy, because there is usually more valve deformity,
calcification, and fibrosis than with the initial procedure.395,477,478 MV replacement should be considered in those
patients with recurrent severe symptoms and severe deformity of the mitral apparatus.
3.4.11. Special Considerations
3.4.11.1. Pregnant Patients
MS often affects young women who are in their childbearing
years. The increased intravascular volume, increased cardiac
output, and tachycardia associated with pregnancy may raise
complex issues in the patient with MS and are reviewed in
Section 5.5.1. Percutaneous mitral valvuloplasty can be
performed with few or no complications to the mother or the
fetus and excellent clinical and hemodynamic results.479
3.4.11.2. Older Patients
An increasing number of older patients now present with
symptomatic MS, most likely due to a change in the natural
history of the disease.383,384 Older patients are more likely to
have heavy calcification and fibrosis of the MV leaflets, with
significant subvalvular fusion. In patients older than 65 years,
the success rate of percutaneous valvotomy is lower (less than
50%) than in prior reports of younger patients. Procedural
mortality is 3%, and there is an increased risk of complications, including pericardial tamponade in 5% and thromboembolism in 3%; however, in selected patients with favorable
valve morphology, the procedure may be done safely with
good intermediate-term results.384 The long-term clinical
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Table 20.
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
e573
Use of Echocardiography for Risk Stratification in Mitral Valve (MV) Prolapse
Study, Year
No. of
Patients
Chandraratna et al., 1984494
86
Nishimura et al., 1985495
237
Marks et al., 1989496
456
Features Examined
MV leaflets greater than
5.1 mm
Outcome
1 Cardiovascular abnormalities (60% vs. 6%; Marfan
syndrome, TVP, MR, dilated ascending aorta)
MV leaflet 5 mm or greater
1 Sum of sudden death, endocarditis, and cerebral embolus
0.02
LVID 60 mm or greater
1 MVR (26% vs. 3.1%)
0.001
MV leaflet 5 mm or greater
1 Endocarditis (3.5% vs. 0%)
0.02
1 Moderate-severe MR (11.9% vs. 0%)
0.001
1 MVR (6.6% vs. 0.7%)
0.02
1 Stroke (7.5% vs. 5.8%)
Takamoto et al., 1991
497
Babuty et al., 1994498
Zuppiroli et al., 1994499
p<
0.001
NS
1 Ruptured chordae (48% vs. 5%)
142
MV leaflet 3 mm or
greater, redundant, low
echo destiny
58
Undefined MV thickening
No relation to complex ventricular arrhythmias
119
MV leaflet greater than 5
mm
1 Complex ventricular arrhythmias
NS
0.001
Reprinted from the ACC/AHA/ASE 2004 Guidelines for the Clinical Application of Echocardiography.
LVID indicates left ventricular internal diameter; MR, mitral regurgitation; MVR, mitral valve replacement; NS, not significant; TVP, tricuspid valve prolapse; and 1,
increase.
improvement is considerably less and mortality is higher in
older than younger patients.480
3.5. Mitral Valve Prolapse
3.5.1. Pathophysiology and Natural History
MVP refers to a systolic billowing of 1 or both mitral leaflets
into the left atrium with or without MR. Utilizing current
echocardiographic criteria for diagnosing MVP (valve prolapse of 2 mm or more above the mitral annulus in the
long-axis parasternal view and other views481), the prevalence
of this entity is 1% to 2.5% of the population.482 MVP occurs
as a clinical entity with or without thickening (5 mm or
greater, measured during diastasis) and with or without MR.
Primary MVP can be familial or nonfamilial. There is
interchordal hooding due to leaflet redundancy that includes
both the rough and clear zones of the involved leaflets.483 The
basic microscopic feature of primary MVP is marked proliferation of the spongiosa, the delicate myxomatous connective
tissue between the atrialis (a thick layer of collagen and
elastic tissue that forms the atrial aspect of the leaflet) and the
fibrosa or ventricularis (dense layer of collagen that forms the
basic support of the leaflet). Myxomatous proliferation of the
acid mucopolysaccharide– containing spongiosa tissue causes
focal interruption of the fibrosa. Secondary effects of the
primary MVP syndrome include fibrosis of the surface of the
MV leaflets, thinning and/or elongation of the chordae
tendineae, and ventricular friction lesions. Fibrin deposits
often form at the MV–left atrial angle.
Familial MVP is transmitted as an autosomal trait,484,485
and several chromosomal loci have been identified.486 – 488
Primary MVP occurs with increased frequency in patients
with Marfan syndrome and other connective tissue diseases.483,489 – 491 It has been speculated that the primary MVP
syndrome represents a generalized disease of connective
tissue. The increased incidence of MVP in Von Willebrand’s
disease and other coagulopathies, primary hypomastia, and
various connective tissue diseases has been used to support
the concept that increased incidence of MVP is a result of
defective embryogenesis of cell lines of mesenchymal origin.492 Thoracic skeletal abnormalities such as straight thoracic spine and pectus excavatum are commonly associated
with MVP.
The auscultatory findings in MVP, when present, may
consist of a click or multiple clicks that move within systole
with changes in LV dimensions and/or a late systolic or
holosystolic murmur of MR. There may be left atrial dilatation and LV enlargement, depending on the presence and
severity of MR. Involvement of other valves may occur.
Tricuspid valve prolapse may occur in 40% of patients with
MVP.485 Pulmonic and aortic valve prolapses occur in 2% to
10% of patients with MVP.483 There is an increased incidence
of associated secundum atrial septal defect and/or left-sided
atrioventricular bypass tracts and supraventricular arrhythmias.
The natural history of asymptomatic MVP is heterogeneous and can vary from benign and normal life expectancy
to adverse with significant morbidity or mortality. The
spectrum of MR ranges from absent to severe. The most
frequent predictor of cardiovascular mortality is moderate to
severe MR and, less frequently, an LV ejection fraction less
than 0.50.493 Echocardiographic evidence of thickened MV
leaflets (5 mm or greater) is also a predictor of complications
related to MVP (Table 20).494 – 499 In most patients, the MVP
syndrome is associated with a benign prognosis.500,501 The
age-adjusted survival rate for both men and women with
MVP is similar to that of individuals without this entity.485
The gradual progression of MR in patients with MVP may
result in the progressive dilatation of the left atrium and
ventricle. Left atrial dilatation may result in atrial fibrillation,
and moderate to severe MR may eventually result in LV
dysfunction and congestive heart failure.502 Pulmonary hypertension may occur, with associated RV dysfunction. In
some patients, after an initially prolonged asymptomatic
interval, the entire process may enter an accelerated phase as
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a result of left atrial and ventricular dysfunction and atrial
fibrillation. In some instances, spontaneous rupture of MV
chordae will occur.502 Infective endocarditis is a serious
complication of MVP, which is the leading predisposing
cardiovascular diagnosis in most series of patients reported
with endocarditis.490,502,503 Because the absolute incidence of
endocarditis is extremely low for the entire population with
MVP, there is much controversy about the risk of endocarditis in MVP.504
Fibrin emboli are responsible in patients with visual
symptoms consistent with involvement of the ophthalmic or
posterior cerebral circulation.505 Several studies have indicated an increased likelihood of cerebrovascular accidents in
patients under age 45 years who have MVP beyond what
would have been expected in a similar population without
MVP.506
Sudden death is a rare complication of MVP, occurring in
fewer than 2% of known cases during long-term followup,495,500 –511 with annual mortality rates less than 1% per
year. The likely cause is a ventricular tachyarrhythmia, given
the finding of increased incidence of complex ventricular
ectopy on ambulatory ECG recordings in patients with MVP
who had sudden death.512,513 Although infrequent, the highest
incidence of sudden death has been reported in the familial
form of MVP; some patients have also been noted to have QT
prolongation.502,514
3.5.2. Evaluation and Management of the Asymptomatic Patient (UPDATED)
Class I
1. Echocardiography is indicated for the diagnosis of
MVP and assessment of MR, leaflet morphology, and
ventricular compensation in asymptomatic patients
with physical signs of MVP. (Level of Evidence: B)
Class IIa
1. Echocardiography can effectively exclude MVP in
asymptomatic patients who have been diagnosed without clinical evidence to support the diagnosis. (Level of
Evidence: C)
2. Echocardiography can be effective for risk stratification in asymptomatic patients with physical signs of
MVP or known MVP. (Level of Evidence: C)
Class III
1. Echocardiography is not indicated to exclude MVP in
asymptomatic patients with ill-defined symptoms in the
absence of a constellation of clinical symptoms or
physical findings suggestive of MVP or a positive
family history. (Level of Evidence: B)
2. Routine repetition of echocardiography is not indicated for the asymptomatic patient who has MVP and
no MR or MVP and mild MR with no changes in
clinical signs or symptoms. (Level of Evidence: C)
The primary diagnostic evaluation of the patient with MVP is
the physical examination.502,515 The principal auscultatory
feature of this syndrome is the midsystolic click, a highpitched sound of short duration. One or more clicks may vary
considerably in intensity and timing in systole according to
LV loading conditions and contractility. Clicks result from
sudden tensing of the MV apparatus as the leaflets prolapse
into the left atrium during systole. The midsystolic click may
be followed by a late systolic murmur that is usually mediumto high-pitched and loudest at the cardiac apex. Occasionally
the murmur has a musical or honking quality. The character
and intensity of the murmur also vary under certain conditions, from brief and almost inaudible to holosystolic and
loud. Dynamic auscultation is often useful for establishing the
diagnosis of MVP syndrome.515 Changes in LV end-diastolic
volume result in changes in the timing of the midsystolic
click(s) and murmur. When end-diastolic volume is decreased
(such as with standing), MVP occurs earlier in systole and the
click–murmur complex occurs shortly after the first heart
sound. In contrast, any maneuver that augments the volume of
blood in the ventricle (such as squatting), reduces myocardial
contractility, or increases LV afterload, lengthens the time from
onset of systole to occurrence of MVP, and the click–murmur
complex moves toward the second heart sound. MVP can be
present in the absence of these classic auscultatory findings, and
the clicks may be intermittent and variable.
Although the ECG may provide some information in
patients with MVP, it is often normal. Nonspecific ST-T
wave changes, T-wave inversions, prominent Q waves, and
prolongation of the QT interval also occur. Continuous
ambulatory ECG recordings or event monitors may be useful
for documenting arrhythmias in patients with palpitations.
They are not indicated as a routine test for asymptomatic
patients. Most of the arrhythmias detected are not life
threatening, and patients often complain of palpitations when
the ambulatory ECG recording shows no abnormality.
Two-dimensional and Doppler echocardiography is the
most useful noninvasive test for defining MVP. Valve prolapse of 2 mm or more above the mitral annulus in the
long-axis parasternal view and other views, and especially
when the leaflet coaptation occurs on the atrial side of the
annular plane, indicates a high likelihood of MVP. There is
disagreement concerning the reliability of echocardiographic
appearance of anterior leaflet billowing when observed only
in the apical 4-chamber view.496,516 Leaflet thickness of 5 mm
or more indicates abnormal leaflet thickness and its added
presence makes MVP even more certain. Leaflet redundancy is
often associated with an enlarged mitral annulus and elongated
chordae tendineae.502 The absence or presence of MR is an
important consideration and MVP is more likely when MR is
detected as a high velocity eccentric jet in late systole.517
Reassurance is a major part of the management of patients
with MVP. Patients with mild or no symptoms and findings of
milder forms of prolapse should be reassured of the benign
prognosis. A normal lifestyle and regular exercise is encouraged.502,515
3.5.3. Evaluation and Management of the Symptomatic
Patient (UPDATED)
Class I
1. Aspirin therapy (75 to 325 mg per day) is recommended for symptomatic patients with MVP who
experience cerebral transient ischemic attacks. (Level
of Evidence: C)
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2. In patients with MVP and atrial fibrillation, warfarin
therapy is recommended for patients aged greater than
65 or those with hypertension, MR murmur, or a
history of heart failure. (Level of Evidence: C)
3. Aspirin therapy (75 to 325 mg per day) is recommended for patients with MVP and atrial fibrillation who
are less than 65 years old and have no history of MR,
hypertension, or heart failure. (Level of Evidence: C)
4. In patients with MVP and a history of stroke, warfarin
therapy is recommended for patients with MR, atrial
fibrillation, or left atrial thrombus. (Level of Evidence: C)
Class IIa
1. In patients with MVP and a history of stroke who do
not have MR, atrial fibrillation, or left atrial thrombus,
warfarin therapy is reasonable for patients with echocardiographic evidence of thickening (5 mm or
greater) and/or redundancy of the valve leaflets. (Level
of Evidence: C)
2. In patients with MVP and a history of stroke, aspirin
therapy is reasonable for patients who do not have MR,
atrial fibrillation, left atrial thrombus, or echocardiographic evidence of thickening (5 mm or greater) or
redundancy of the valve leaflets. (Level of Evidence: C)
3. Warfarin therapy is reasonable for patients with MVP
with transient ischemic attacks despite aspirin therapy.
(Level of Evidence: C)
4. Aspirin therapy (75 to 325 mg per day) can be beneficial
for patients with MVP and a history of stroke who have
contraindications to anticoagulants. (Level of Evidence: B)
Class IIb
1. Aspirin therapy (75 to 325 mg per day) may be considered for patients in sinus rhythm with echocardiographic
evidence of high-risk MVP. (Level of Evidence: C)
Some patients consult their physicians about 1 or more of the
common symptoms that occur with this syndrome: palpitations, often reported at a time when continuous ambulatory
ECG recordings show no arrhythmias; atypical chest pain that
rarely resembles classic angina pectoris; dyspnea and fatigue,
when objective exercise testing often fails to show any
impairment in exercise tolerance; and neuropsychiatric complaints, with many patients having panic attacks and similar
syndromes.502 Bankier and Littman report that a significant
number of patients with agoraphobia also have MVP; that
45% of patients with panic disorder have MVP; and that
significant predictors for palpitations in these patients are
depression, poor self-rated health, alcohol intoxication in
women, and heavy coffee drinking and physical inactivity in
men.519
Transient cerebral ischemic episodes occur with increased
incidence in patients with MVP, and some patients develop
stroke syndromes. Reports of amaurosis fugax, homonymous
field loss, and retinal artery occlusion have been described;
occasionally, the visual loss persists.506,520 –522
The roles of cardiac auscultation and echocardiography in
the assessment of symptomatic patients with mitral valve
prolapse are the same as for patients without symptoms.
e575
Patients with MVP and palpitations associated with mild
tachyarrhythmias or increased adrenergic symptoms and
those with chest pain, anxiety, or fatigue often respond to
therapy with beta blockers.523 In many cases, however, the
cessation of stimulants such as caffeine, alcohol, and cigarettes may be sufficient to control symptoms. In patients with
recurrent palpitations, continuous or event-activated ambulatory ECG recordings may reveal the presence or absence of
arrhythmias at the time of symptoms and indicate appropriate
treatment of existing arrhythmias. The indications for electrophysiological testing are similar to those in the general
population (e.g., aborted sudden death, recurrent syncope of
unknown cause, and symptomatic or sustained ventricular
tachycardia).524
Orthostatic symptoms due to postural hypotension and
tachycardia are best treated with volume expansion, preferably by liberalizing fluid and salt intake. Mineralocorticoid
therapy or clonidine may be needed in severe cases, and it
may be beneficial to have the patient wear support stockings.
Daily aspirin therapy (75 to 325 mg per day) is recommended for MVP patients with documented transient focal
neurological events who are in sinus rhythm with no atrial
thrombi. Such patients also should avoid cigarettes and oral
contraceptives. The American Stroke Association
guidelines524a recommend aspirin for patients with MVP who
have experienced an ischemic stroke (Class IIa, Level of
Evidence: C), based on the evidence of efficacy of antiplatelet
agents for general stroke patients. No randomized trials have
addressed the efficacy of selected antithrombotic therapies for
the specific subgroup of stroke patients with MVP. In the
current guidelines, the committee recommends aspirin for
those post-stroke patients with MVP who have no evidence of
MR, atrial fibrillation, left atrial thrombus, or echocardiographic evidence of thickening (5 mm or greater) or redundancy of the valve leaflets. However, long-term anticoagulation therapy with warfarin is recommended (Class I) for
post-stroke patients with MVP who have MR, atrial fibrillation, or left atrial thrombus. In the absence of these indications, warfarin is also recommended (Class IIa) in post-stroke
patients with MVP who have echocardiographic evidence of
thickening (5 mm or greater) or redundancy of the valve
leaflets and in MVP patients who experience recurrent transient ischemic attacks while taking aspirin. In each of these
situations, the international normalized ratio (INR) should be
maintained between 2.0 and 3.0). In MVP patients with atrial
fibrillation, warfarin therapy is indicated in patients aged
greater than 65 years and in those with MR, hypertension, or
a history of heart failure (INR 2.0 to 3.0). Aspirin therapy is
satisfactory in patients with atrial fibrillation who are younger
than 65 years old, have no MR, and have no history of
hypertension or heart failure.525,526 Daily aspirin therapy is
often recommended for patients with high-risk echocardiographic characteristics.
A normal lifestyle and regular exercise are encouraged for
most patients with MVP, especially those who are asymptomatic.511,526 Whether exercise-induced ischemia develops
in some patients with MVP remains controversial.527,528
Restriction from competitive sports is recommended when
moderate LV enlargement, LV dysfunction, uncontrolled
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tachyarrhythmias, long-QT interval, unexplained syncope,
prior resuscitation from cardiac arrest, or aortic root enlargement is present individually or in combination.502 A familial
occurrence of MVP should be explained to the patient and is
particularly important in those with associated disease who
are at greater risk for complications. There is no contraindication to pregnancy based on the diagnosis of MVP alone.
Asymptomatic patients with MVP and no significant MR
can be evaluated clinically every 3 to 5 years. Serial echocardiography is not necessary in most patients and is recommended only in patients who have high-risk characteristics on
the initial echocardiogram and in those who develop symptoms consistent with cardiovascular disease or who have a
change in physical findings that suggests development of
significant MR. Patients who have high-risk characteristics,
including those with moderate to severe MR, should be
followed up once a year.
Patients with severe MR with symptoms or impaired LV
systolic function require cardiac catheterization and evaluation for MV surgery (see Section 3.6.4.2). The thickened,
redundant MV can often be repaired rather than replaced with
a low operative mortality and excellent short- and long-term
results.529,530 Follow-up studies also suggest lower thrombotic
and endocarditis risk with valve repair than with prosthetic
valves.
3.5.4. Surgical Considerations
Management of MVP may require valve surgery, particularly
in those patients who develop a flail mitral leaflet due to
rupture of chordae tendineae or their marked elongation.
Most such valves can be repaired successfully by surgeons
experienced in MV repair, especially when the posterior
leaflet of the MV is predominantly affected. MV repair for
MR due to MVP is associated with excellent long-term
survival and remains superior to MV replacement beyond 10
years and up to 20 years after surgery.529,530 Anterior leaflet
MV repair is associated with a higher risk for reoperation than
posterior leaflet repair. As noted in Section 3.6.4.2, cardiologists are strongly encouraged to refer patients who are
candidates for complex MV repair to surgical centers experienced in performing MV repair. Residual MR is associated
with a higher risk for reoperation.530 Symptoms of heart
failure, severity of MR, presence or absence of atrial fibrillation, LV systolic function, LV end-diastolic and endsystolic volumes, and pulmonary artery pressure (rest and
exercise) all influence the decision to recommend MV surgery. Recommendations for surgery in patients with MVP
and MR are the same as for those with other forms of
nonischemic severe MR. For further detail, please review
Section 7.3. on MV surgery.
3.6. Mitral Regurgitation
3.6.1. Etiology
The common causes of organic MR include MVP syndrome,
rheumatic heart disease, CAD, infective endocarditis, certain
drugs, and collagen vascular disease. MR may also occur
secondary to a dilated annulus from dilatation of the left
ventricle. In some cases, such as ruptured chordae tendineae,
ruptured papillary muscle, or infective endocarditis, MR may
be acute and severe. Alternatively, MR may worsen gradually
over a prolonged period of time. These 2 ends of the spectrum
have quite different clinical presentations.
3.6.2. Acute Severe Mitral Regurgitation
3.6.2.1. Pathophysiology
In acute severe MR, a sudden volume overload is imposed on
the left atrium and left ventricle. Acute volume overload
increases LV preload, allowing for a modest increase in total
LV stroke volume.531 However, in the absence of compensatory eccentric hypertrophy (which has had no time to develop), forward stroke volume and cardiac output are reduced. At the same time, the unprepared left atrium and left
ventricle cannot accommodate the regurgitant volume, which
causes large v waves in the left atrium and results in
pulmonary congestion. In this phase of the disease, the patient
has both reduced forward output (even shock) and simultaneous pulmonary congestion. In severe MR, the hemodynamic overload often cannot be tolerated, and MV repair or
replacement must often be performed urgently.
3.6.2.2. Diagnosis
The patient with acute severe MR is almost always severely
symptomatic. Physical examination of the precordium may be
misleading, because a normal-sized left ventricle does not
produce a hyperdynamic apical impulse. The systolic murmur
of MR may not be holosystolic and may even be absent. A
third heart sound or early diastolic flow rumble may be the
only abnormal physical finding present. Transthoracic echocardiography may demonstrate the disruption of the MV and
help provide semiquantitative information on lesion severity;
however, transthoracic echocardiography may underestimate
lesion severity by inadequate imaging of the color flow jet.
Thus, if there is hyperdynamic systolic function of the left
ventricle on a transthoracic echocardiogram in a patient with
acute heart failure, the suspicion of severe MR should be
raised. Because transesophageal echocardiography can more
accurately assess the color flow jet,532 transesophageal imaging should be performed if MV morphology and regurgitant
severity are still in question after transthoracic echocardiography. Transesophageal echocardiography is also helpful in
demonstrating the anatomic cause of acute severe MR and
directing successful surgical repair.
In the hemodynamically stable patient, if CAD is suspected
or there are risk factors for CAD (see Section 10.2), coronary
arteriography is necessary before surgery because myocardial
revascularization should be performed during MV surgery in
those patients with concomitant CAD.533,534
3.6.2.3. Medical Therapy
In acute severe MR, medical therapy has a limited role and is
aimed primarily to stabilize hemodynamics in preparation for
surgery. The goal of nonsurgical therapy is to diminish the
amount of MR, in turn increasing forward output and reducing pulmonary congestion. In the normotensive patient, administration of nitroprusside may effectively accomplish all 3
goals. Nitroprusside increases forward output not only by
preferentially increasing aortic flow but also by partially
restoring MV competence as LV size diminishes.535,536 In the
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patient rendered hypotensive because of a severe reduction in
forward output, nitroprusside should not be administered
alone, but combination therapy with an inotropic agent (such
as dobutamine) and nitroprusside is of benefit in some patients.
In such patients, aortic balloon counterpulsation increases forward output and mean arterial pressure while diminishing
regurgitant volume and LV filling pressure and can be used to
stabilize the patient while they are prepared for surgery. If
infective endocarditis is the cause of acute MR, identification
and treatment of the infectious organism are essential.
3.6.3. Chronic Asymptomatic Mitral Regurgitation
3.6.3.1. Pathophysiology and Natural History
Patients with mild to moderate MR may remain asymptomatic with little or no hemodynamic compromise for many
years; however, MR from a primary MV abnormality tends to
progress over time with an increase in volume overload due
to an increase in the effective orifice area. Progression of the
MR is variable and determined by progression of lesions or
mitral annulus size.537
Once the MR has become severe, there has been time for
development of eccentric cardiac hypertrophy in which new
sarcomeres are laid down in series, which increases the length
of individual myocardial fibers.228,531 The resulting increase
in LV end-diastolic volume is compensatory because it
permits an increase in total stroke volume, which allows for
restoration of forward cardiac output.538 At the same time, the
increase in LV and left atrial size allows accommodation of
the regurgitant volume at a lower filling pressure, and the
symptoms of pulmonary congestion abate. In this phase of
compensated MR, the patient may be entirely asymptomatic,
even during vigorous exercise. It should be noted that in the
compensatory phase, augmented preload and reduced or
normal afterload (provided by the unloading of the left
ventricle into the left atrium) facilitate LV ejection, which
results in a large total stroke volume and a normal forward
stroke volume.
The compensated phase of MR is variable but may last
for many years. However, the prolonged burden of volume
overload may eventually result in LV dysfunction. In this
phase, contractile dysfunction impairs ejection, and endsystolic volume increases. There may be further LV
dilatation and increased LV filling pressure. These hemodynamic events result in reduced forward output and pulmonary
congestion. However, the still favorable loading conditions often
maintain ejection fraction in the low normal range (0.50 to 0.60)
despite the presence of significant muscle dysfunction.531,539,540
Correction of MR should be performed before the advanced
phases of LV decompensation.
Numerous studies indicate that patients with chronic severe MR have a high likelihood of developing symptoms or LV
dysfunction over the course of 6 to 10 years.518,526,541,542 However, the incidence of sudden death in asymptomatic patients
with normal LV function varies widely among these studies.
The natural history of severe MR due to a flail posterior
leaflet has been documented.518 At 10 years, 90% of patients
are dead or require MV operation. The mortality rate in
patients with severe MR caused by flail leaflets is 6% to 7%
per year. However, patients at risk of death are predominantly
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those with LV ejection fractions less than 0.60 or with NYHA
functional class III–IV symptoms, and less so those who are
asymptomatic and have normal LV function.518,543 Severe
symptoms also predict a poor outcome after MV repair or
replacement.543
3.6.3.2. Diagnosis
In evaluating the patient with chronic MR, the history is
invaluable. A well-established estimation of baseline exercise
tolerance is important in gauging the subtle onset of symptoms at subsequent evaluations. Physical examination should
demonstrate displacement of the LV apical impulse, which
indicates that MR is severe and chronic, producing cardiac
enlargement. A third heart sound or early diastolic flow
rumble is usually present and does not necessarily indicate
LV dysfunction. Findings consistent with pulmonary hypertension are worrisome because they indicate advanced disease with worsened prognosis.544 An ECG and chest X-ray
are useful in establishing rhythm and for assessment of the
pulmonary vascularity and pulmonary congestion.
3.6.3.3. Indications for Transthoracic Echocardiography
Class I
1. Transthoracic echocardiography is indicated for baseline evaluation of LV size and function, RV and left
atrial size, pulmonary artery pressure, and severity of
MR (Table 4) in any patient suspected of having MR.
(Level of Evidence: C)
2. Transthoracic echocardiography is indicated for delineation of the mechanism of MR. (Level of Evidence: B)
3. Transthoracic echocardiography is indicated for annual or semiannual surveillance of LV function (estimated by ejection fraction and end-systolic dimension)
in asymptomatic patients with moderate to severe MR.
(Level of Evidence: C)
4. Transthoracic echocardiography is indicated in patients
with MR to evaluate the MV apparatus and LV function
after a change in signs or symptoms. (Level of Evidence: C)
5. Transthoracic echocardiography is indicated to evaluate LV size and function and MV hemodynamics in the
initial evaluation after MV replacement or MV repair.
(Level of Evidence: C)
Class IIa
1. Exercise Doppler echocardiography is reasonable in
asymptomatic patients with severe MR to assess exercise
tolerance and the effects of exercise on pulmonary artery
pressure and MR severity. (Level of Evidence: C)
Class III
1. Transthoracic echocardiography is not indicated for
routine follow-up evaluation of asymptomatic patients
with mild MR and normal LV size and systolic function. (Level of Evidence: C)
An initial comprehensive 2D, Doppler echocardiogram is
indispensable in the management of the patient with MR. The
echocardiogram provides a baseline estimation of LV and left
atrial size, an estimation of LV ejection fraction, and approx-
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imation of the severity of regurgitation.2 Quantification of the
severity of MR (Table 4)27 is strongly recommended.27,541,545,546 In the majority of patients, an estimate of
pulmonary artery pressure can be obtained from the TR peak
velocity.547 Changes from these baseline values are subsequently used to guide the timing of MV surgery. The blood
pressure at the time of each study should be documented,
because the afterload on the ventricle will affect the measured
severity of the MR.
The initial transthoracic echocardiogram should disclose
the anatomic cause of the MR. A central color flow jet of MR
with a structurally normal MV apparatus suggests the presence of functional MR, which may be due to annular
dilatation from LV dilatation or tethering of the posterior
leaflet because of regional LV dysfunction in patients with
ischemic heart disease. An eccentric color flow jet of MR
with abnormalities of the MV apparatus indicates organic
MR. In patients with organic MR, the echocardiogram should
assess the presence of calcium in the annulus or leaflets, the
redundancy of the valve leaflets, and the MV leaflet involved
(anterior leaflet, posterior leaflet, or bileaflet). These factors
will help determine the feasibility of valve repair if surgery is
contemplated. The system proposed by Carpentier548 allows
the echocardiographer to focus on the anatomic and physiologic characteristics of the valve that aid the surgeon in
planning the repair. The valve dysfunction is described on the
basis of the motion of the free edge of the leaflet relative to
the plane of the annulus: type I, normal; type II, increased, as
in MVP; type IIIA, restricted during systole and diastole, and
type IIIB, restricted during systole.
The diagnosis of severe MR should be made by correlating
the findings on physical examination with the findings from a
comprehensive 2D, Doppler echocardiogram. Multiple parameters from the Doppler examination should be used to diagnose
severe MR (Table 4),27 including the color flow jet width and
area, the intensity of the continuous-wave Doppler signal, the
pulmonary venous flow contour, the peak early mitral inflow
velocity, and quantitative measures of effective orifice area and
regurgitation volume.2 In addition, there should be enlargement
of the left ventricle and left atrium in chronic severe MR.
Abnormalities of the MV apparatus are often present if there is
severe MR, but ischemic LV dysfunction may also result in
severe MR. If a discrepancy is present, or if the patient has poor
windows on transthoracic echocardiography, then further evaluation of the severity of MR is required, including cardiac
catheterization, magnetic resonance imaging, or transesophageal
echocardiography.
3.6.3.4. Indications for Transesophageal Echocardiography
(See Also Section 8.1.4.)
Class I
1. Preoperative or intraoperative transesophageal echocardiography is indicated to establish the anatomic
basis for severe MR in patients in whom surgery is
recommended to assess feasibility of repair and to
guide repair. (Level of Evidence: B)
2. Transesophageal echocardiography is indicated for
evaluation of MR patients in whom transthoracic
echocardiography provides nondiagnostic information
regarding severity of MR, mechanism of MR, and/or
status of LV function. (Level of Evidence: B)
Class IIa
1. Preoperative transesophageal echocardiography is reasonable in asymptomatic patients with severe MR who
are considered for surgery to assess feasibility of
repair. (Level of Evidence: C)
Class III
1. Transesophageal echocardiography is not indicated for
routine follow-up or surveillance of asymptomatic patients with native valve MR. (Level of Evidence: C)
3.6.3.5. Serial Testing
The aim of serial follow-up of the patient with MR is to
subjectively assess changes in symptomatic status and objectively assess changes in LV function and exercise tolerance
that can occur in the absence of symptoms. Asymptomatic
patients with mild MR and no evidence of LV enlargement,
LV dysfunction, or pulmonary hypertension can be followed
on a yearly basis with instructions to alert the physician if
symptoms develop in the interim. Yearly echocardiography is
not necessary unless there is clinical evidence that MR has
worsened. In patients with moderate MR, clinical evaluation
including echocardiography should be performed annually
and sooner if symptoms occur.
Asymptomatic patients with severe MR should be followed up with history, physical examination, and echocardiography every 6 to 12 months to assess symptoms or
transition to asymptomatic LV dysfunction. Exercise stress
testing may be used to add objective evidence regarding
symptoms and changes in exercise tolerance. Exercise testing
is especially important if a good history of the patient’s
exercise capacity cannot be obtained. Measurement of pulmonary artery pressure and assessment of severity of MR
during exercise may be helpful.
Interpretation of LV ejection fraction in the patient with
MR is made difficult because the loading conditions present
in MR facilitate ejection and increase ejection fraction, the
standard guide to LV function. Nonetheless, several studies
have indicated that the preoperative ejection fraction is an
important predictor of postoperative survival in patients with
chronic MR.539,544,549 –551 Ejection fraction in a patient with
MR with normal LV function is usually greater than or equal to
0.60. Consistent with this concept, postoperative ventricular
function is lower and survival is reduced in patients with a
preoperative ejection fraction less than 0.60 compared with
patients with higher ejection fractions.550,551
Alternatively or in concert, echocardiographic LV endsystolic dimension (or volume) can be used in the timing of
MV surgery. End-systolic dimension, which may be less load
dependent than ejection fraction,552 should be less than 40
mm preoperatively to ensure normal postoperative LV function.538,551–553 If patients become symptomatic, they should
undergo MV surgery even if LV function is normal.
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3.6.3.6. Guidelines for Physical Activity and Exercise
Recommendations regarding participation in competitive athletics were published by the Task Force on Acquired Valvular
Heart Disease of the 36th Bethesda Conference.138 Asymptomatic patients with MR of any severity who are in sinus
rhythm and who have normal LV and left atrial dimensions
and normal pulmonary artery pressure may exercise without
restriction.138 However, those with definite LV enlargement
(greater than or equal to 60 mm), pulmonary hypertension, or
any degree of LV systolic dysfunction at rest should not
participate in any competitive sports.
3.6.3.7. Medical Therapy
In the asymptomatic patient with chronic MR, there is no
generally accepted medical therapy. Although intuitively, the
use of vasodilators may appear to be logical for the same
reasons that they are effective in acute MR, there are no large,
long-term studies to indicate that they are beneficial. Furthermore, because MR with normal ejection fraction is a disease
in which afterload is not increased,230,538,554,555 drugs that
reduce afterload might produce a physiological state of
chronic low afterload with which there is very little experience. There has not been a consistent improvement in LV
volumes and severity of MR in the small studies that have
examined the effect of ACE inhibitors.312,556 –558 The beneficial effect seen in some studies may be more related to
blockade of tissue angiotensin rather than the vasodilatory
effect of the drug.559 Thus, in the absence of systemic
hypertension, there is no known indication for the use of
vasodilating drugs or ACE inhibitors in asymptomatic patients with MR and preserved LV function.
However, in patients with functional or ischemic MR
(resulting from dilated or ischemic cardiomyopathy), there is
reason to believe that preload reduction may be
beneficial.535 If LV systolic dysfunction is present, primary
treatment of the LV systolic dysfunction with drugs such as
ACE inhibitors or beta blockers (particularly carvedilol) and
biventricular pacing have all been shown to reduce the
severity of functional MR.560 –563
In patients with MR who develop symptoms but have
preserved LV function, surgery is the most appropriate therapy.
If atrial fibrillation develops, heart rate should be controlled with
rate-lowering calcium channel blockers, beta blockers, digoxin,
or, rarely, amiodarone. In patients with severe MR and chronic
atrial fibrillation, a Maze procedure may be added to an MV
repair (see Section 3.6.4.2.4), because this will reduce the risk of
postoperative stroke. Although the risk of embolism with the
combination of MR and atrial fibrillation was formerly considered similar to that of MS and atrial fibrillation, subsequent
studies suggest that embolic risk may be less in MR.564,565
Nonetheless, it is recommended that the INR be maintained at 2
to 3 in this population.
3.6.3.8. Indications for Cardiac Catheterization
Class I
1. Left ventriculography and hemodynamic measurements are indicated when noninvasive tests are incon-
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clusive regarding severity of MR, LV function, or the
need for surgery. (Level of Evidence: C)
2. Hemodynamic measurements are indicated when pulmonary artery pressure is out of proportion to the
severity of MR as assessed by noninvasive testing.
(Level of Evidence: C)
3. Left ventriculography and hemodynamic measurements are indicated when there is a discrepancy between clinical and noninvasive findings regarding severity of MR. (Level of Evidence: C)
4. Coronary angiography is indicated before MV repair
or MV replacement in patients at risk for CAD. (Level
of Evidence: C)
Class III
1. Left ventriculography and hemodynamic measurements
are not indicated in patients with MR in whom valve
surgery is not contemplated. (Level of Evidence: C)
Cardiac catheterization, with or without exercise, is necessary
when there is a discrepancy between clinical and noninvasive
findings. Catheterization is also performed when surgery is
contemplated in cases in which there is still some doubt about
the severity of MR after noninvasive testing or when there is
a need to assess extent and severity of CAD preoperatively. In
patients with MR who have risk factors for CAD (e.g.,
advanced age, hypercholesterolemia, or hypertension) or
when there is a suspicion that MR is ischemic in origin (either
because of known myocardial infarction or suspected ischemia), coronary angiography should be performed before
surgery.
Patients should usually not undergo valve surgery unless
the degree of MR is severe. If there is a discrepancy regarding
the severity of MR between the physical examination or
elements of the comprehensive 2D, Doppler examination,
then transesophageal echocardiography, magnetic resonance
imaging, or left ventriculography should be performed. Although the standard semiquantitative approach to determining
the severity of MR from ventriculography has its own
limitations,566 ventriculography does provide an additional
method to assess LV dilatation and function and gauge the
severity of MR. Exercise hemodynamics may provide additional information that is helpful in decision making.
During the catheterization procedure, a right-heart catheterization should be performed if the severity of MR is
uncertain to obtain right-sided pressures to quantify the
increase in left atrial pressure (pulmonary artery wedge
pressure) and pulmonary artery pressure. The presence or
absence of a large v wave has little diagnostic impact when
combined with data from the rest of the catheterization.567
3.6.4. Indications for Surgery
3.6.4.1. Types of Surgery
Three different MV operations are currently used for correction of MR: 1) MV repair; 2) MV replacement with preservation of part or all of the mitral apparatus; and 3) MV
replacement with removal of the mitral apparatus. Each
procedure has its advantages and disadvantages, and there-
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fore, the indications for each procedure are somewhat
different.
In most cases, MV repair is the operation of choice when
the valve is suitable for repair and appropriate surgical skill
and expertise are available. This procedure preserves the
patient’s native valve without a prosthesis and therefore
avoids the risk of chronic anticoagulation (except in patients
in atrial fibrillation) or prosthetic valve failure late after
surgery. Additionally, preservation of the mitral apparatus
leads to better postoperative LV function and survival than in
cases in which the apparatus is disrupted.545,568 –573 Improved
postoperative function occurs with repair because the mitral
apparatus is an integral part of the left ventricle that is
essential for maintenance of normal shape, volume, and
function of the left ventricle.574 However, MV repair is
technically more demanding than MV replacement, may
require longer extracorporeal circulation time, and may occasionally fail. Valve morphology and surgical expertise are
of critical importance for the success of valve repair (see
below).
The reoperation rate after MV repair is similar to the
reoperation rate after MV replacement.530 There is a 7% to
10% reoperation rate at 10 years in patients undergoing MV
repair, usually for severe recurrent MR.530,575–578 Approximately 70% of the recurrent MR is thought to be due to the
initial procedure and 30% to progressive valve disease.575 The
reoperation rate is lower in those patients who had the initial
operation for posterior leaflet abnormalities than in those who
had bileaflet or anterior leaflet abnormalities.518,577
The advantage of MV replacement with preservation of the
chordal apparatus is that this operation ensures postoperative
MV competence, preserves LV function, and enhances postoperative survival compared with MV replacement, in which
the apparatus is disrupted.570,579 –582 The disadvantage is the
use of a prosthetic valve, with the risks of deterioration
inherent in tissue valves or the need for anticoagulation
inherent in mechanical valves.
MV replacement in which the MV apparatus is resected
should almost never be performed. It should only be performed in those circumstances in which the native valve and
apparatus are so distorted by the preoperative pathology
(rheumatic disease, for example) that the mitral apparatus
cannot be spared. As noted previously (Section 3.4.9), artificial chordal reconstruction does extend the opportunities for
repair in some such patients with rheumatic MR.467,468
The advantages of MV repair make it applicable across the
full spectrum of MR, including the 2 extremes of the
spectrum. Valve repair might be possible in patients with
far-advanced symptomatic MR and depressed LV function
because it preserves LV function at the preoperative level572;
MV replacement with disruption of the apparatus in such
patients could lead to worsened or even fatal LV dysfunction
after surgery. At the other extreme, in the relatively asymptomatic patient with well-preserved LV function, repair of a
severely regurgitant valve might be contemplated to avoid the
onset of ventricular dysfunction from longstanding volume
overload.583 However, failed MV repair would result in the
need for a prosthetic valve; this would represent a clear
complication, because it would impose the risks of a prosthe-
sis on a patient who did not previously require it. Hence,
“prophylactic” surgery in an asymptomatic patient with MR
and normal LV function requires a high likelihood of successful repair.
3.6.4.2. Indications for Mitral Valve Operation
Class I
1. MV surgery is recommended for the symptomatic
patient with acute severe MR.* (Level of Evidence: B)
2. MV surgery is beneficial for patients with chronic
severe MR* and NYHA functional class II, III, or IV
symptoms in the absence of severe LV dysfunction
(severe LV dysfunction is defined as ejection fraction
less than 0.30) and/or end-systolic dimension greater
than 55 mm. (Level of Evidence: B)
3. MV surgery is beneficial for asymptomatic patients
with chronic severe MR* and mild to moderate LV
dysfunction, ejection fraction 0.30 to 0.60, and/or endsystolic dimension greater than or equal to 40 mm.
(Level of Evidence: B)
4. MV repair is recommended over MV replacement in the
majority of patients with severe chronic MR* who require surgery, and patients should be referred to surgical
centers experienced in MV repair. (Level of Evidence: C)
Class IIa
1. MV repair is reasonable in experienced surgical centers
for asymptomatic patients with chronic severe MR* with
preserved LV function (ejection fraction greater than
0.60 and end-systolic dimension less than 40 mm) in
whom the likelihood of successful repair without residual
MR is greater than 90%. (Level of Evidence: B)
2. MV surgery is reasonable for asymptomatic patients
with chronic severe MR,* preserved LV function, and
new onset of atrial fibrillation. (Level of Evidence: C)
3. MV surgery is reasonable for asymptomatic patients
with chronic severe MR,* preserved LV function, and
pulmonary hypertension (pulmonary artery systolic
pressure greater than 50 mm Hg at rest or greater than
60 mm Hg with exercise). (Level of Evidence: C)
4. MV surgery is reasonable for patients with chronic severe
MR* due to a primary abnormality of the mitral apparatus and NYHA functional class III–IV symptoms and
severe LV dysfunction (ejection fraction less than 0.30
and/or end-systolic dimension greater than 55 mm) in
whom MV repair is highly likely. (Level of Evidence: C)
Class IIb
1. MV repair may be considered for patients with chronic
severe secondary MR* due to severe LV dysfunction
(ejection fraction less than 0.30) who have persistent
NYHA functional class III–IV symptoms despite optimal therapy for heart failure, including biventricular
pacing. (Level of Evidence: C)
*See Table 4.27
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Class III
1. MV surgery is not indicated for asymptomatic patients
with MR and preserved LV function (ejection fraction
greater than 0.60 and end-systolic dimension less than
40 mm) in whom significant doubt about the feasibility
of repair exists. (Level of Evidence: C)
2. Isolated MV surgery is not indicated for patients with
mild or moderate MR. (Level of Evidence: C)
In many cases, the type of operation, MV repair versus
replacement, is important in timing surgery. In fact, although
the type of surgery to be performed is never actually
established until the operation, many situations lend themselves to preoperative prediction of the operation that can be
performed. This prediction is based on the skill and experience of the surgeon in performing repair and on the location
and type of MV disease that caused the MR. Nonrheumatic
posterior leaflet prolapse due to degenerative MV disease or
a ruptured chordae tendineae can usually be repaired using a
resection of the portion of the valve and an annuloplasty.584,585 Involvement of the anterior leaflet or both
anterior and posterior leaflets diminishes the likelihood of
repair because the operation requires other interventions, such
as chordal shortening, chordal transfer, and innovative anatomic repairs.586 –591 Consequently, the skill and experience of
the surgeon are probably the most important determinants of
the eventual operation that will be performed. In general,
rheumatic involvement of the MV and calcification of the
MV leaflets or annulus diminish the likelihood of repair, even
in experienced hands.592
The number of patients undergoing MV repair for MR has
increased steadily over the past decade in the United States
and Canada in relation to the number undergoing MV
replacement. However, among isolated MV procedures reported in the STS National Cardiac Database from 1999 to
2000,593 the frequency of repair was only 35.7% (3027 of a
total of 8486 procedures), which suggests that MV repair is
underutilized. The STS National Database also indicates an
operative mortality rate of under 2% in patients undergoing
isolated MV repair in 2004, which compares favorably to the
greater than 6% operative mortality rate for patients undergoing isolated MV replacement.165 Considering the beneficial
effect of MV repair on survival and LV function, cardiologists
are strongly encouraged to refer patients who are candidates
for MV repair to surgical centers experienced in performing
MV repair.
3.6.4.2.1. Symptomatic Patients With Normal Left Ventricular Function. Patients with symptoms of congestive heart
failure despite normal LV function on echocardiography
(ejection fraction greater than 0.60 and end-systolic dimension less than 40 mm) require surgery. Surgery should be
performed in patients with mild symptoms and severe MR
(Fig. 8), especially if it appears that MV repair rather than
replacement can be performed. The feasibility of repair is
dependent on several factors, including valve anatomy and
surgical expertise. Successful surgical repair improves symptoms, preserves LV function, and avoids the problems of a
prosthetic valve. When repair is not feasible, MV replace-
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ment with chordal preservation should relieve symptoms and
maintain LV function.
3.6.4.2.2. Asymptomatic or Symptomatic Patients With Left
Ventricular Dysfunction. Preoperative variables that are predictive of postoperative survival, symptomatic improvement,
and postoperative LV function are summarized in Table
21.538,539,544,549 –552 The timing of surgery for asymptomatic
patients is controversial, but most would now agree that MV
surgery is indicated with the appearance of echocardiographic
indicators of LV dysfunction. These include LV ejection
fraction less than or equal to 0.60 and/or LV end-systolic
dimension greater than or equal to 40 mm (Fig. 8). Surgery
performed at this time will likely prevent further deterioration
in LV function and improve longevity. This is true whether
repair or replacement is performed,551 although repair is
clearly preferred. It must be emphasized that, unlike with the
timing of AVR for AR, LV ejection fraction should not be
allowed to fall into the lower limit of the normal range in
patients with chronic MR.551,594 –596 The data regarding postoperative survival are much stronger with LV ejection fraction than with end-systolic dimension,544,549 –551 whereas both
ejection fraction and end-systolic dimension strongly influence postoperative LV function and heart failure.538,539,544,551,552 MV surgery should also be recommended
for symptomatic patients with evidence of LV systolic dysfunction (ejection fraction less than or equal to 0.60, and/or
end-systolic dimension greater than or equal to 40 mm).
Determining the surgical candidacy of the symptomatic
patient with MR and far-advanced LV dysfunction is a
common clinical dilemma. The question that often arises is
whether the patient with MR has such advanced LV dysfunction that he or she is no longer a candidate for surgery. Often
such cases present difficulty in distinguishing primary cardiomyopathy with secondary MR from primary MR with secondary myocardial dysfunction. In the latter case, if MV
repair appears likely, surgery should still be contemplated
(Fig. 8). Even though such a patient is likely to have
persistent LV dysfunction, surgery is likely to improve
symptoms and prevent further deterioration of LV function.328 If MV replacement is necessary in such patients, it
should be performed only if the chordal apparatus can be
preserved. The modification of MV geometry by an “undersized” annular ring in patients with severe LV dysfunction and significant functional MR may be beneficial in a
subset of patients with primary myocardial disease,597– 602
although the impact on outcomes compared with aggressive medical therapy, including beta blockers and cardiac
resynchronization therapy,560 –563 has not been studied in a
prospective randomized trial.
3.6.4.2.3. Asymptomatic Patients With Normal Left Ventricular Function. As noted previously, repair of a severely
regurgitant valve may be contemplated in an asymptomatic
patient with severe MR and normal LV function to preserve
LV size and function and prevent the sequelae of chronic
severe MR.541 Although there are no randomized data with
which to recommend this approach to all patients, the
committee recognizes that some experienced centers are
moving in this direction for patients for whom the likelihood
of successful repair is high. Natural history studies indicate
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Figure 8. Management strategy for patients with chronic severe mitral regurgitation.
*Mitral valve (MV) repair may be performed in asymptomatic patients with normal left ventricular (LV) function if performed by an experienced surgical team and if the likelihood of successful MV repair is greater than 90%. AF indicates atrial fibrillation; Echo, echocardiography; EF, ejection fraction; ESD, end-systolic dimension; eval, evaluation; HT, hypertension; and MVR, mitral valve replacement.
uniformly that asymptomatic patients with severe MR and
normal LV function have a high likelihood of developing
symptoms and/or LV dysfunction warranting operation over
the course of 6 to 10 years.518,526,541,542 Two recent studies
have also addressed the risk of sudden death541,542 in asymptomatic patients with severe MR and normal LV function. In
a long-term retrospective study in which severity of MR was
quantified by Doppler echocardiography,541 198 patients with
an effective orifice area greater than 40 mm2 had a 4% per
year risk of cardiac death during a mean follow-up period of
2.7 years. However, in the second study of 132 patients
followed up prospectively for 5 years, during which the
indications for surgery were symptoms, development of LV
dysfunction (ejection fraction less than 0.60), LV dilatation
(LV end-systolic dimension greater than 45 mm), atrial
fibrillation, or pulmonary hypertension, there was only 1
cardiac death in an asymptomatic patient, but this patient had
refused surgery which was indicated by development of LV
dilation.542
MV repair is often recommended in hemodynamically
stable patients with newly acquired severe MR, such as might
occur with ruptured chordae. Surgery is also recommended in
an asymptomatic patient with chronic MR with recent onset
of atrial fibrillation in whom there is a high likelihood of
successful valve repair (see below).
Surgery for asymptomatic patients with severe MR and
normal LV function should only be considered if there is a
greater than 90% likelihood of successful valve repair in a
center experienced in this procedure. As noted above, cardiologists are strongly encouraged to refer patients who are
candidates for MV repair to surgical centers experienced in
performing MV repair.
3.6.4.2.4. Atrial Fibrillation. Atrial fibrillation is a common,
potentially morbid arrhythmia associated with MR. In patients with MR due to MVP, there is a high risk of development of atrial fibrillation. The development of atrial fibrillation is independently associated with a high risk of cardiac
death or heart failure.603 Preoperative atrial fibrillation is an
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Table 21.
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
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Preoperative Predictors of Surgical Outcome in Mitral Regurgitation
Study, Year
Study
Design
Schuler et al., 1979539
Retrospective
Type of
Surgery
No. of
Patients
MVR
20
Outcome Assessed
LV function
Findings
12 Patients with average LV EF 0.70 had normal
postoperative EF; 4 patients with average EF 0.58
had postoperative EF 0.25
Phillips et al., 1981549
Retrospective
MVR
105
Survival
EF less than 0.50 predicted poor survival
Zile et al., 1984538
Prospective
MVR
16
Heart failure, LV
function
LV ESD index greater than 2.6 cm per m2 (45 mm)
and LV FS less than 0.32 predicted poor outcome
Crawford et al., 1990544
Prospective
MVR
48
Survival, LV function
LV EF less than 0.50 predicted reduced survival; ESV
less than 50 ml per m2 predicted persistent LV
dilatation
Wisenbaugh et al., 1994552
Registry
MVR
26
Survival, LV function
ESD, EDD, and FS predicted poor survival and LV
function; only ESD significant in multivariate
analysis
Enriquez-Sarano et al., 1994550
Retrospective
Survival
LV EF 0.60 or less predicted poor survival whether
MVR or CP was performed; EF estimated by echo
FS or visual analysis
Enriquez-Sarano et al., 1994551
Retrospective
LV function
EF, ESD, LV diameter/thickness ratio, and endsystolic wall stress predicted outcome; EF
estimated by echo FS or visual analysis
MVR-CP
35
MVR
214
MV repair
195
MVR
104
MV repair
162
CP indicates chordal sparing procedure; echo, echocardiographic; EDD, end-diastolic dimension; EF, ejection fraction; ESD, end-systolic dimension; ESV, end-systolic
volume; FS, fractional shortening; LA, left atrial; LV, left ventricular; MV, mitral valve; MVR, mitral valve replacement; and PAWP, pulmonary artery wedge pressure.
independent predictor of reduced long-term survival after
MV surgery for chronic MR.551,603– 605 The persistence of
atrial fibrillation after MV surgery can lead to thromboembolism and partially nullifies an advantage of mitral repair by
requiring anticoagulation.605 Predictors of the persistence of
atrial fibrillation after successful valve surgery are the presence of atrial fibrillation for greater than 1 year and left atrial
size greater than 50 mm.606 In 1 study, an even shorter
duration of preoperative atrial fibrillation (3 months) was a
predictor of persistent atrial fibrillation after MV repair607;
persistent atrial fibrillation after surgery occurred in 80% of
patients with preoperative atrial fibrillation greater than or
equal to 3 months but in no patient with preoperative atrial
fibrillation less than 3 months. Although patients who develop atrial fibrillation also usually manifest other symptomatic or functional changes that would warrant MV operation,
many clinicians would consider the recent onset of atrial
fibrillation to be an indication in and of itself for surgery, if
there is a high likelihood of valve repair (Fig. 8).582,607 In
patients presenting for MV operation with chronic atrial
fibrillation, a concomitant Maze procedure may prevent
future thromboembolic events by restoring normal sinus
rhythm.608 – 614 The decision to proceed with a Maze procedure should be based on the age and health of the patient, as
well as the surgical expertise, because this procedure may add
to the morbidity of the operation.
3.6.5. Ischemic Mitral Regurgitation
The outlook for the patient with ischemic MR is substantially
worse than that for regurgitation from other causes.533,615 A
worse prognosis accrues from the fact that ischemic MR is
usually caused by LV dysfunction resulting from myocardial
infarction. Furthermore, the MV itself is usually anatomically
normal, and MR is secondary to papillary muscle displacement and tethering of the mitral leaflet(s). The mechanism of
MR in chronic ischemic disease is local LV remodeling
(apical and posterior displacement of papillary muscles),
which leads to excess valvular tenting and loss of systolic
annular contraction.616 – 623 The indication for MV operation
in the patient who undergoes CABG with mild to moderate
MR is still unclear, but there are data to indicate benefit of
MV repair in such patients.624 – 627 Patients with ischemic
heart disease who have MR have a worse prognosis than
those who do not have MR.628 – 631 CABG alone may improve
LV function and reduce ischemic MR in selected patients,629,632 especially those with transient severe MR due to
ischemia, in whom myocardial revascularization can eliminate episodes of severe MR. However, CABG alone is
usually insufficient and leaves many patients with significant
residual MR, and these patients would benefit from concomitant MV repair at the time of the CABG.623– 627,633– 642 Mitral
annuloplasty alone with a downsized annuloplasty ring is
often effective at relieving MR.637,638,641
In severe MR secondary to acute myocardial infarction,
hypotension and pulmonary edema often occur. Severe MR
occurs in 6% to 7% of patients with cardiogenic shock.643 The
cause of the MR should be established, because the MR may
be due to a ruptured papillary muscle, papillary muscle
displacement with leaflet tethering, or annular dilatation from
severe LV dilatation. Those patients with an acute rupture of
the papillary muscle should undergo surgery on an emergency basis, with either valve repair or MV replacement.644 In
those patients with papillary muscle dysfunction, treatment
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should initially consist of hemodynamic stabilization, usually
with insertion of an intra-aortic balloon pump. Surgery should
be considered for those patients who do not improve with
aggressive medical therapy. Correction of acute severe ischemic MR usually requires valve surgery in addition to
revascularization. The best operation for ischemic MR is
controversial,645,646 but MV repair with an annuloplasty ring
is the best approach in most instances.624,627,633– 642
3.6.6. Evaluation of Patients After Mitral Valve
Replacement or Repair
After MV surgery, follow-up is necessary to detect late
surgical failure and assess LV function, as discussed in
Section 9.3. For patients in whom a bioprosthesis has been
inserted, the specter of eventual deterioration is always
present and must be anticipated. If a mechanical valve has
been inserted, anticoagulation is required, and chronic surveillance of prothrombin time and INR is necessary. After
valve repair, follow-up to assess the effectiveness of the repair
is indicated early, especially because most repair failures are
detected soon after surgery.
3.6.7. Special Considerations in the Elderly
Elderly patients with MR fare more poorly with valve surgery
than do their counterparts with AS. In general, operative
mortality increases and survival is reduced in patients older
than 75 years of age, especially if MV replacement must be
performed or if the patient has concomitant CAD or other
valve lesions.164,167,545,647– 650 Operative mortality in the elderly is low in experienced centers,651 but the overall operative mortality for MV replacement in this age group in the
United States exceeds 14%167,649,650 and is particularly high
(greater than 20%) in low-volume centers.167 Although the
risks are reduced if MV repair is performed rather than MV
replacement, the majority of patients in this age group require
concomitant CABG.650 The average operative risk for combined MV repair plus CABG in the United States is 8%,165
which will undoubtedly be higher in the older population.
These risks are worth taking in patients with significant
symptoms. However, under most circumstances, asymptomatic patients or patients with mild symptoms should be treated
medically.
3.7. Multiple Valve Disease
3.7.1. Introduction
Remarkably few data exist to objectively guide the management of mixed valve disease. The large number of combined
hemodynamic disturbances (and their varied severity) yields
a large number of potential combinations to consider, and few
data exist for any specific category. Hence, each case must be
considered individually, and management must be based on
understanding the potential derangements in hemodynamics
and LV function and the probable benefit of medical versus
surgical therapy. Other than recommending evaluation with
physical examination, echocardiography, and cardiac catheterization as clinically indicated for patient evaluation and
management, the committee has developed no specific recommendations in this section.
3.7.2. Mixed Single Valve Disease
3.7.2.1. Pathophysiology
In mixed mitral or aortic valve disease, 1 lesion usually
predominates over the other, and the pathophysiology resembles that of the pure dominant lesion. Thus, for the patient
with mixed AS and AR in whom stenosis predominates, the
pathophysiology and management resemble that of pure AS.
The left ventricle develops concentric hypertrophy rather than
dilatation. The timing of AVR is based on symptomatic
status. However, if the attendant regurgitation is more than
mild, it complicates the pathophysiology by placing the
concentrically hypertrophied and noncompliant left ventricle
on a steeper portion of its diastolic pressure-volume curve, in
turn causing pulmonary congestion. The effect is that neither
lesion by itself might be considered severe enough to warrant
surgery, but both together produce substantial hemodynamic
compromise that necessitates intervention.
In patients with severe AR and mild AS, the high total
stroke volume due to extensive regurgitation may produce a
substantial transvalvular gradient. Because the transvalvular
gradient varies with the square of the transvalvular flow,139 a
high gradient in predominant AR may be predicated primarily
on excess transvalvular flow rather than on a severely
compromised orifice area.
In mixed mitral disease, predominant MS produces a left
ventricle of normal volume, whereas in predominant MR,
chamber dilatation occurs. A substantial transvalvular gradient may exist in regurgitation-predominant disease because of
high transvalvular flow, but, as in mixed aortic valve disease
with predominant regurgitation, the gradient does not represent severe orifice stenosis.
3.7.2.2. Diagnosis
3.7.2.2.1. Two-Dimensional and Doppler Echocardiographic Studies. As noted above, chamber geometry is
important in assessing the dominant lesion (stenotic versus
regurgitant), which in turn is important in management. For
instance, a small left ventricle is inconsistent with chronic
severe regurgitation. Doppler interrogation of the aortic valve
and MVs with mixed disease should provide a reliable
estimate of the transvalvular mean gradient; however, there
may be a significant discrepancy between the Dopplerderived maximum instantaneous gradient and catheter peak
gradient with mixed aortic valve disease. Exercise hemodynamics derived by Doppler echocardiography have been
helpful in managing mixed valve disease. MV area can be
measured accurately by the half-time method in mixed
MS/MR. Aortic valve area would be measured inaccurately at
the time of cardiac catheterization in mixed AS/AR if cardiac
output were measured by either thermodilution or the Fick
method. The valve area can be measured more accurately by
the continuity equation from Doppler echocardiography in
mixed AS/AR; however, the continuity equation calculation
of valve area may not be completely independent of flow.652
Although these valve area measurements by Doppler echocardiography are more accurate than those obtained at cardiac
catheterization, in general, the confusing nature of mixed
valve disease makes cardiac catheterization necessary to
obtain additional hemodynamic information in most patients.
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3.7.2.2.2. Cardiac Catheterization. Catheterization is often
necessary to fully assess hemodynamics. The diagnosis of
“moderate” mixed disease is frequently made on the basis of
noninvasive tests alone. This term suggests that the valve
disease is not severe enough to mandate surgery. However, as
noted previously, the nondominant lesion may exacerbate the
pathophysiology of the dominant lesion and produce symptoms. In this context, a complete hemodynamic evaluation
that includes exercise hemodynamics may be important. For
example, resting hemodynamics in mixed mitral disease
might show a transmitral gradient of 5 mm Hg, a valve area
of 1.5 cm2, and 2⫹ MR, with a resting pulmonary artery
wedge pressure of 15 mm Hg. However, with exercise, the
wedge pressure can increase dramatically, identifying a
hemodynamic cause for the patient’s symptoms and suggesting that mechanical correction will be of benefit. Many cases
of mixed valve disease require hemodynamic exercise testing
to delineate proper assessment.653
Hemodynamic estimation of valve area requires determination of total valve flow and transvalvular gradient. The presence
of valvular regurgitation in a primarily stenotic valve causes
forward cardiac output to underestimate total valve flow, which
is the sum of forward plus regurgitant flow. Thus, if standard
measures of forward cardiac output (e.g., thermodilution or Fick
method) are used to calculate valve area, the area will be
underestimated. One approach to this problem is to use total
stroke volume (angiographic end-diastolic volume minus endsystolic volume) in place of forward stroke volume (Fick or
thermodilution cardiac output/heart rate) in the Gorlin formula.
Although this approach is logically valid, it has not been
clinically tested or vetted against a “gold standard.” Furthermore, angiographic stroke volume is dependent on accurate
calculation of cardiac volumes, which can be difficult in the very
large and/or spherical left ventricles encountered in valvular
regurgitation.654 In general, the utility of this approach is limited.
Doppler pressure half-time may be very useful in this situation.
3.7.2.3. Management
Unlike the management of a severe pure valve lesion, solid
guidelines for mixed disease are difficult to establish. The
most logical approach is to surgically correct disease that
produces more than mild symptoms or, in the case of
-dominant aortic valve disease, to operate in the presence of
even mild symptoms. In regurgitant dominant lesions, surgery can be delayed until symptoms develop or asymptomatic
LV dysfunction (as gauged by markers used in pure regurgitant disease) becomes apparent. The use of vasodilators to
forestall surgery in patients with asymptomatic mixed disease
is untested. Anticoagulants should be used in mixed mitral
disease if atrial fibrillation is present. In mixed mitral disease
with moderate or severe (3⫹ to 4⫹) regurgitation, percutaneous mitral balloon valvotomy is contraindicated because
regurgitation may worsen.
3.7.3. Combined Mitral Stenosis and
Aortic Regurgitation
3.7.3.1. Pathophysiology
When both AR and MS coexist, severe MS usually coexists
with mild AR with pathophysiology similar to that of isolated
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MS. However, the coexistent AR is occasionally severe. The
combination of coexistent severe MS and severe AR may
present confusing pathophysiology and often leads to misdiagnosis. MS restricts LV filling, blunting the impact of AR on
LV volume.341 Thus, even severe AR may fail to cause a
hyperdynamic circulation, so that typical signs of AR are
absent during physical examination. Likewise, echocardiographic LV cavitary dimensions may be only mildly enlarged.
Doppler half-time measurements of MV area may be inaccurate in the presence of significant AR. The picture presented
by this complex combination of lesions usually requires all
diagnostic modalities, including cardiac catheterization, for
resolution.
3.7.3.2. Management
Mechanical correction of both lesions is eventually necessary
in most patients. Development of symptoms or pulmonary
hypertension is the usual indication for intervention. Combined aortic valve and MV replacement is a reasonable
approach, but when correction is anticipated in patients with
predominant MS, balloon mitral valvotomy followed by AVR
may be performed. This obviates the need for double-valve
replacement, which has a higher risk of perioperative mortality and postoperative complications than single-valve replacement.165 In most cases, it is advisable to perform mitral
valvotomy first and then monitor the patient for symptomatic
improvement. If symptoms disappear, correction of AR can
be delayed.
3.7.4. Combined Mitral Stenosis and
Tricuspid Regurgitation
3.7.4.1. Pathophysiology
When TR coexists with MS, some elements of pulmonary
hypertension are also usually present. Thus, the issue arises
whether TR will or will not improve when MS is corrected
and pulmonary artery pressure decreases.655 Unfortunately,
the status of the tricuspid valve after correction of MS is
difficult to predict. In general, if pulmonary hypertension is
severe and the tricuspid valve anatomy is not grossly distorted, improvement in TR can be expected after correction of
MS.656 On the other hand, if there is severe rheumatic
deformity of the tricuspid valve, dilatation of the tricuspid
annulus, or severe TR, competence is likely to be restored
only by surgery.
3.7.4.2. Diagnosis
Once TR is suspected by physical examination to coexist with
MS, both can be further evaluated by Doppler echocardiographic studies. The presence of TR almost guarantees that an
estimation of pulmonary artery pressure can be made by
Doppler interrogation of the tricuspid valve. An evaluation of
the anatomy of both the mitral and tricuspid valves can be
made.
3.7.4.3. Management
If the MV anatomy is favorable for percutaneous balloon
valvotomy and there is concomitant pulmonary hypertension,
valvotomy should be performed regardless of symptom status. After successful mitral valvotomy, pulmonary hypertension and TR almost always diminish.656
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If MV surgery is performed, concomitant tricuspid annuloplasty should be considered, especially if there are preoperative signs or symptoms of right-sided heart failure, rather
than risking severe persistent TR, which may necessitate a
second operation.657 If intraoperative assessment suggests
that TR is functional without significant dilatation of the
tricuspid annulus, it may not be necessary to perform an
annuloplasty. However, there is growing evidence that TR
associated with dilatation of the tricuspid annulus should be
repaired.658,659 Tricuspid dilatation is an ongoing process that
may progress to severe TR if untreated. Annuloplasty of the
tricuspid valve based on tricuspid dilatation improves functional status independent of the degree of TR.658 Residual TR
after tricuspid annuloplasty is determined principally by the
degree of preoperative tricuspid leaflet tethering.660
3.7.5. Combined Mitral Regurgitation and
Aortic Regurgitation
3.7.5.1. Pathophysiology
As noted in the previous discussions of isolated MR and AR,
these are 2 very different diseases with different pathophysiological effects and different guidelines for the timing of
surgery. Thus, in the patient with double-valve regurgitation,
proper management becomes problematic. The most straightforward approach is the same as for mixed single-valve
disease, that is, to determine which lesion is dominant and to
treat primarily according to that lesion. Although both lesions
produce LV dilatation, AR will produce modest systemic
systolic hypertension and a mild increase in LV wall
thickness.
3.7.5.2. Diagnosis and Therapy
Doppler echocardiographic interrogation shows bivalve regurgitation and an enlarged left ventricle. 2D echocardiography is usually performed to assess the severity of AR and
MR, LV size and function, left atrial size, pulmonary artery
pressure, and feasibility of MV repair. When surgery is
required, AVR plus MV repair is the preferred strategy when
MV repair is possible.661
3.7.6. Combined Mitral Stenosis and Aortic Stenosis
3.7.6.1. Pathophysiology
Combined stenotic disease is almost always secondary to
rheumatic heart disease. Obstruction of flow at the MV
diminishes aortic valve flow as well. Thus, the problem of
evaluating aortic valve severity in a low-flow/low-gradient
situation often exists.
3.7.6.2. Diagnosis and Therapy
In patients with significant AS and MS, the physical findings
of AS generally dominate, and those of MS may be overlooked, whereas the symptoms are usually those of MS.
Noninvasive evaluation should be performed with 2D and
Doppler echocardiographic studies to evaluate the severity of
AS and MS, paying special attention to suitability for mitral
balloon valvotomy in symptomatic patients, and to assess
ventricular size and function. If the degree of AS appears to
be mild and the MV is acceptable for balloon valvotomy, this
should be attempted first. If mitral balloon valvotomy is
successful, the aortic valve should then be re-evaluated.
3.7.7. Combined Aortic Stenosis and Mitral Regurgitation
3.7.7.1. Pathophysiology
Combined AS and MR often develop secondary to rheumatic
heart disease. However, congenital AS and MVP may occur
in combination in younger patients, as may degenerative AS
and MR in the elderly. If severe, AS will worsen the degree
of MR. In addition, MR may cause difficulty in assessing the
severity of AS because of reduced forward flow. MR will also
enhance LV ejection performance, thereby masking the early
development of LV systolic dysfunction caused by AS.
Development of atrial fibrillation and loss of atrial systole
may further reduce forward output because of impaired filling
of the hypertrophied left ventricle.
3.7.7.2. Diagnosis and Therapy
Noninvasive evaluation should be performed with 2D and
Doppler echocardiography to evaluate the severity of both AS
and MR. Attention should be paid to LV size, wall thickness,
and function; left atrial size; right-heart function; and pulmonary artery pressure. Particular attention should be paid to
MV morphology in patients with these combined lesions.
Patients with severe AS and severe MR (with abnormal MV
morphology) with symptoms, LV dysfunction, or pulmonary
hypertension should undergo combined AVR and MV replacement or MV repair. AVR plus MV repair is the preferred
strategy when MV repair is possible.661 However, in patients
with severe AS and lesser degrees of MR, the severity of MR
may improve greatly after isolated AVR, particularly when
there is normal MV morphology. Intraoperative transesophageal echocardiography and, if necessary, visual inspection of
the MV should be performed at the time of AVR to determine
whether additional MV surgery is warranted in these patients.
In patients with mild to moderate AS and severe MR in
whom surgery on the MV is indicated because of symptoms,
LV dysfunction, or pulmonary hypertension, preoperative
assessment of the severity of AS may be difficult because of
reduced forward stroke volume. If the mean aortic valve
gradient is greater than 30 mm Hg, AVR should be performed. In patients with less severe aortic valve gradients,
inspection of the aortic valve and its degree of opening on 2D
or transesophageal echocardiography and visual inspection
by the surgeon may be important in determining the need for
concomitant AVR.
3.8. Tricuspid Valve Disease
3.8.1. Pathophysiology
Tricuspid valve dysfunction can occur with normal or abnormal valves. When normal tricuspid valves develop dysfunction, the resulting hemodynamic abnormality is almost always pure regurgitation. This occurs with elevation of RV
systolic and/or diastolic pressure, RV cavity enlargement, and
tricuspid annular dilatation662,663; RV systolic hypertension
occurs in MS, pulmonic valve stenosis, and the various
causes of pulmonary hypertension. RV diastolic hypertension
occurs in dilated cardiomyopathy, RV infarction, and RV
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failure of any cause.662,663 Pacemaker-induced severe TR is
rare but may require intervention.
Abnormalities of the tricuspid valve leading to TR can
occur with rheumatic valvulitis, infective endocarditis, carcinoid, rheumatoid arthritis, radiation therapy, trauma (such as
repeated endomyocardial biopsies), Marfan syndrome, tricuspid valve prolapse, tricuspid annular dilatation, or congenital
disorders such as Ebstein’s anomaly663 or a cleft tricuspid
valve as part of atrioventricular canal malformations. Anorectic drugs may also cause TR (see Section 3.9).
Tricuspid stenosis is most commonly rheumatic in origin.
On very rare occasions, infective endocarditis (with large
bulky vegetations), congenital abnormalities, carcinoid, Fabry’s disease, Whipple’s disease, or previous methysergide
therapy may be implicated.664 Right atrial mass lesions
represent a nonvalvular cause of obstruction to the tricuspid
orifice and may also over time destroy the leaflets and cause
regurgitation. Rheumatic tricuspid involvement usually results in both stenosis and regurgitation.
3.8.2. Diagnosis
The clinical features of tricuspid stenosis include a giant a
wave and diminished rate of y descent in the jugular venous
pulse, a tricuspid opening snap, and a murmur that is
presystolic as well as middiastolic and that increases on
inspiration.665 Because chronic rheumatic valve disease is the
most common cause of tricuspid stenosis, there is usually
associated mitral and/or aortic disease, and the clinical
findings include those associated with the other 2 valves,
especially the MV.
The clinical features of TR include abnormal systolic c and
v waves in the jugular venous pulse, a lower left parasternal
systolic murmur (holosystolic or less than holosystolic, depending on the severity of hemodynamic derangement) that
may increase on inspiration (Carvallo’s sign), a middiastolic
murmur in severe regurgitation, and systolic hepatic pulsation. In rare instances, severe TR may produce systolic
propulsion of the eyeballs,666 pulsatile varicose veins,667 or a
venous systolic thrill and murmur in the neck.668 Other
associated clinical features are related to the cause of TR.
Moderate or severe TR may be present without the classic
clinical features.
Echocardiography is valuable in assessing tricuspid valve
structure and motion, measuring annular size, and identifying
other cardiac abnormalities that might influence tricuspid
valve function. Doppler echocardiography permits estimation
of the severity of TR,669 RV systolic pressure, and the
tricuspid valve diastolic gradient. Although echocardiography
is a valuable diagnostic tool, it should be pointed out that
clinically insignificant TR is detected by color Doppler
imaging in many normal persons.16,19 –22 This is not an
indication for either routine follow-up or prophylaxis against
bacterial endocarditis. Clinical correlation and judgment must
accompany the echocardiographic results. Systolic pulmonary artery pressures greater than 55 mm Hg are likely to
cause TR with anatomically normal tricuspid valves, whereas
TR occurring with systolic pulmonary artery pressures less than
40 mm Hg is likely to reflect a structural abnormality of the
valve apparatus. Systolic pulmonary artery pressure estimation
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combined with information about annular circumference will
further improve the accuracy of clinical assessment.662
3.8.3. Management
Class I
1. Tricuspid valve repair is beneficial for severe TR in
patients with MV disease requiring MV surgery. (Level
of Evidence: B)
Class IIa
1. Tricuspid valve replacement or annuloplasty is reasonable for severe primary TR when symptomatic. (Level
of Evidence: C)
2. Tricuspid valve replacement is reasonable for severe
TR secondary to diseased/abnormal tricuspid valve
leaflets not amenable to annuloplasty or repair. (Level
of Evidence: C)
Class IIb
1. Tricuspid annuloplasty may be considered for less than
severe TR in patients undergoing MV surgery when
there is pulmonary hypertension or tricuspid annular
dilatation. (Level of Evidence: C)
Class III
1. Tricuspid valve replacement or annuloplasty is not indicated in asymptomatic patients with TR whose pulmonary artery systolic pressure is less than 60 mm Hg in the
presence of a normal MV. (Level of Evidence: C)
2. Tricuspid valve replacement or annuloplasty is not
indicated in patients with mild primary TR. (Level of
Evidence: C)
The patient’s clinical status and the cause of the tricuspid
valve abnormality usually determine the appropriate therapeutic strategy. Medical and/or surgical management may be
required. For example, in the patient with severe MS and
pulmonary hypertension with resulting RV dilatation and TR,
relief of MS and the resulting decrease in pulmonary artery
pressure may result in substantial diminution of the degree of
TR. The timing of surgical intervention for TR remains
controversial, as do the surgical techniques. To some extent,
this controversy has diminished since the advent of 2D and
Doppler echocardiography for preoperative diagnosis and
assessment. Intraoperative transesophageal Doppler echocardiography allows refinement of annuloplasty techniques to
optimize outcome.670 – 672 At present, surgery on the tricuspid
valve for TR occurs commonly at the time of MV surgery. As
noted in Section 3.7.4.3, TR associated with dilatation of the
tricuspid annulus should be repaired,658,659 because tricuspid
dilatation is an ongoing process that may progress to severe
TR if left untreated.
Tricuspid valve balloon valvotomy has been advocated for
tricuspid stenosis of various causes.673– 675 However, severe
TR is a common consequence of this procedure, and results
are poor when severe TR develops.
Patients with severe TR of any cause have a poor long-term
outcome because of RV dysfunction and/or systemic venous
congestion.676 Tricuspid valve and chordal reconstruction can be
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attempted in some cases of TR resulting from endocarditis and
trauma.677– 679 In recent years, annuloplasty has become an
established surgical approach to significant TR.657– 660,680 – 684
When the valve leaflets themselves are diseased, abnormal,
or destroyed, valve replacement with a low-profile mechanical valve or bioprosthesis is often necessary.685 A biological
prosthesis is preferred because of the high rate of thromboembolic complications with mechanical prostheses in the
tricuspid position. In patients with associated conduction
defects, insertion of a permanent epicardial pacing electrode
at the time of valve replacement can avoid the later need to
pass a transvenous lead across the prosthetic valve.
3.9. Drug-Related Valvular Heart Disease
In addition to the common causes of the valvular lesions
described in the preceding sections, there are a number of
uncommon causes related to systemic diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid antibody syndrome, and ankylosing spondylitis), drugs (e.g., ergotamine, methysergide, anorexiant
medications, and pergolide), and toxins. It is beyond the
scope of these guidelines to discuss the specific pathology
and natural history of valve disease stemming from each of
these many causes. In general, the evaluation and management
strategies for patients with valve disease related to these disorders are directed both toward the underlying systemic process
when appropriate and to the diagnosis and treatment of the
associated valvular disease according to the guidelines developed for each of the valve lesions as described in Section 3.
The sympathomimetic appetite-suppressant drug fenfluramine and its pure d-enantiomer, dexfenfluramine, were removed from the market in September 1997 after several
reports of unusual left-sided valvular heart disease (AR and
MR) linked to these agents.686 – 690 These medications, when
used alone or in combination with the noradrenergic agent
phentermine, had been previously implicated as a cause of
pulmonary hypertension, even when used for less than 1
month.691– 693 The echocardiographic and histopathological
findings reported were similar to those described in patients
with carcinoid or ergotamine-induced valvular heart disease.694 – 699 The fibroproliferative response appears to be
mediated via the 5-HT2B receptor.700 Subsequent reports have
estimated a lower prevalence of anorexiant drug–related
valvulopathy meeting Food and Drug Administration (FDA)
criteria and have identified age, dose, and duration of exposure as risk factors for its development.701–706 In the metaanalysis by Sachdev and colleagues, the pooled prevalence of
qualifying valvular regurgitation among patients treated for
more than 90 days was 12.0% compared with 5.9% for the
unexposed group (odds ratio 2.2, 95% confidence interval
1.7–2.7).707 This increase was primarily the result of mild or
greater AR (exposed 9.6% and unexposed 4.5%, odds ratio
2.5, 95% confidence interval 1.9 –3.3). The prevalence among
patients exposed for less than 90 days was 6.8% compared
with 5.8% for unexposed patients (odds ratio 1.4, 95%
confidence interval 0.8 –2.4).707 Isolated reports have implied
that the valvular disease associated with combination- or
single-drug therapy does not progress and may improve after
cessation of treatment.708,709 Concomitant therapy with a
selective serotonin reuptake inhibitor for depression or panic
disorder does not appear to confer incremental risk.703 Fewer
patients are now presenting for initial evaluation since the
drugs were removed from the market in 1997. To date, an
excess prevalence of valvular heart disease has not been
reported for sibutramine, a serotonin and norepinephrine
reuptake inhibitor, or for phentermine when used as monotherapy for obesity.710,711 The lipase inhibitor orlistat is not
known to produce valvular disease. There are now several
reports of a carcinoid-like valvulopathy in Parkinson’s disease patients treated with pergolide, a dopamine-receptor
agonist.712–714 A history of exposure to any of the ergotaminelike agents briefly reviewed here should prompt a careful
cardiovascular examination, echocardiography when indicated, and treatment as would be dictated by the nature and
severity of the heart valve lesion(s).
3.10. Radiation Heart Disease
Mediastinal radiation may produce cardiac valve abnormalities that usually become evident at least 5 years after the
radiation injury. The assessment and treatment of these
patients can be difficult in part because these valve lesions
occur within a context of multiple cardiac and noncardiac
abnormalities produced by radiation. Radiation-induced valvular lesions are based on calcification of valve leaflets and
the fibrous skeleton of the heart. Mixed aortic valve disease
that combines stenosis and insufficiency is the most common
lesion, but MR and TR may also occur. Nonvalvular aspects
of radiation-induced heart disease include a restrictive cardiomyopathy, aortic and great vessel calcification, coronary
artery stenoses including ostial lesions and diffuse lesions,
pericardial constriction, and conduction abnormalities. Noncardiac abnormalities such as skin and sternal necrosis,
recurrent pleural effusions, and radiation-induced pulmonary
dysfunction can also play a role in the overall picture.
Valve dysfunction is often part of a presenting picture of
congestive heart failure and dyspnea, but the relative contributions of valve dysfunction and restrictive cardiomyopathy
may be difficult to separate. In addition, recurrent pleural
effusions are often prominent, and radiation-induced pulmonary dysfunction can occur. Thus, for these patients, dyspnea
is a multifactorial problem.
For patients with radiation heart disease, surgery for any
cardiac lesion should be approached with caution.715 First,
symptom relief secondary to valve surgery may be incomplete because the restrictive cardiomyopathy may limit improvement of congestive heart failure symptoms, and pulmonary dysfunction may contribute to ongoing symptoms of
dyspnea. Second, surgical risks are increased for patients with
radiation heart disease both from cardiac disease and noncardiac conditions, such as aortic calcification and skin necrosis.
Thus, logic dictates that patients be significantly symptomatic
before undergoing surgery or have substantial jeopardy from
severe coronary artery lesions. Third, reoperation for a patient
with mediastinal radiation is an extremely difficult issue,
because the radiation injury appears to be ongoing after a
primary operation, creating severe mediastinal adhesions and
an increased risk of reoperation.715 The most common indication for surgery for patients with radiation heart disease is
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CAD, a common cause of late mortality after mediastinal
radiation. During coronary artery surgery, even moderately
dysfunctional aortic valves should be replaced to avoid the
dangers of early reoperation in the future.716 Aortic and aortic
root calcification can make even primary surgery for AVR
difficult, and the lack of aortic root enlargement may limit the
size of a prosthesis that can be implanted. Overall, radiation
heart disease constitutes one of the most difficult management
problems in acquired heart disease, and patients with this
condition should be evaluated in centers with experience in
its management.717
4. Evaluation and Management of Infective
Endocarditis
Class I
1. Patients at risk for infective endocarditis who have
unexplained fever for more than 48 h should have at
least 2 sets of blood cultures obtained from different
sites. (Level of Evidence: B)
Class III
1. Patients with known valve disease or a valve prosthesis
should not receive antibiotics before blood cultures are
obtained for unexplained fever. (Level of Evidence: C)
Infective endocarditis may be suspected in a patient with a
cardiac murmur suggestive of organic valvular or congenital
heart disease or in a patient with a prosthetic heart valve by
the presence of fever, anemia, hematuria, and physical findings such as petechiae, Osler’s nodes, Janeway lesions, Roth
spots, splenomegaly, and splinter hemorrhages. A definitive
diagnosis may be made with positive blood cultures and/or
characteristic echocardiographic findings. The diagnosis of
infective endocarditis is often imprecise, because bacteremia
can occur without endocardial infection, and endocarditis can
occur with negative blood cultures, especially if a patient has
received antibiotics for minor undiagnosed febrile illness.30
The role of echocardiography has emerged with visualization
of vegetation by transthoracic echocardiography in approximately 60% to 75% of patients and by transesophageal
echocardiography in more than 95% of patients.718
Criteria for the diagnosis of infective endocarditis were
proposed by Van Reyn et al.719 based on the combination of
blood cultures, clinical signs, and symptoms. Durack et al
proposed a new set of diagnostic criteria that placed echocardiographic findings of endocardial lesions on an equal footing
as positive blood cultures.720 The Duke criteria designated a
patient as “definite,” “rejected,” or “possible” with regard to
the likelihood of infective endocarditis. Because the designation of “possible” infective endocarditis seemed overly broad
based on 1 minor criterion if the patient did not meet
requirements for “rejected,”721 a more recent modification of
the Duke criteria has been developed with the intent to
improve diagnostic specificity without sacrificing sensitivity.722 These modified Duke criteria are shown in Table 22,
which defines major and minor criteria, and in Table 23,
which uses the diagnostic classifications of definite, possible,
or rejected.
e589
The diagnosis of infective endocarditis in a patient with a
pathological murmur or a valvular prosthesis and unexplained
fever lasting more than 72 h should include an assessment for
vascular and immunologic phenomena, 3 to 5 sets of blood
cultures, and a transthoracic echocardiogram. When the
echocardiogram is technically inadequate, is nondiagnostic,
or is negative for infective endocarditis, transesophageal
echocardiography should be obtained.
4.1. Antimicrobial Therapy
Antimicrobial therapy in endocarditis is guided by identification of the causative organism. The majority (80%) of cases
of endocarditis are due to streptococcal and staphylococcal
organisms. The latter species is also the most frequent
organism in endocarditis resulting from intravenous drug
abuse. Eighty percent of tricuspid valve infection is by
Staphylococcus aureus. This organism is also a frequent
cause of infective endocarditis in patients with insulindependent diabetes mellitus. With prosthetic valve endocarditis, a wide spectrum of organisms can be responsible within
the first year of operation. However, in “early” prosthetic
valve endocarditis, usually defined as endocarditis during the
first 2 months after surgery, Staphylococcus epidermidis is
the predominant offending organism. Late-onset prosthetic
valve endocarditis follows the profile of native valve endocarditis, that is, streptococci (viridans) and staphylococci.
Enterococcus faecalis and E. faecium account for 90% of
enterococcal endocarditis, which is usually associated with
malignancy or manipulation of the genitourinary or gastrointestinal tract. Gram-positive and Gram-negative bacilli are
relatively uncommon causes of endocarditis. In recent years,
the HACEK group of organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella species) has
become an important cause of endocarditis. These organisms
cause large vegetations (greater than 1 cm), large-vessel
embolism, and congestive heart failure. They should be
considered along with fungal endocarditis when large vegetations are noted. Fungi, especially Candida, are important
causes of endocarditis in patients with prosthetic valves,
compromised immune systems, and intravenous drug abuse.
Several of the AHA recommendations for antimicrobial
regimens, updated in 2005, are given in Tables 24 through
29.723 Complete treatment regimens for resistant organisms
are provided in that statement from the AHA which can be found
at http://www.americanheart.org/presenter.jhtml?identifier⫽
2158.723
4.2. Culture-Negative Endocarditis
Culture-negative endocarditis most frequently (62%) results
from prior antibiotic treatment before blood cultures are
drawn.724,725 Other reasons for negative blood cultures include infections due to Candida; Aspergillus; other fastidious,
slow-growing organisms726 such as Q-fever and Bartonella
organisms; and noninfective endocarditis such as LibmanSacks endocarditis in patients with systemic lupus erythematosus. A proposed regimen for culture-negative, presumed
bacterial endocarditis723 is shown in Table 30.
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Table 22.
October 7, 2008
Definition of Terms Used in the Proposed Modified Duke Criteria for the Diagnosis of Infective Endocarditis*
Major criteria
Blood culture positive for IE
Typical microorganisms consistent with IE from 2 separate blood cultures:
Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or
Community-acquired enterococci in the absence of a primary focus; or
Microorganisms consistent with IE from persistently positive blood cultures, defined as follows:
At least 2 positive cultures of blood samples drawn more than 12 h apart; or
All of 3 or a majority of greater than 4 separate cultures of blood (with first and last sample drawn at least 1 h apart)
Single positive blood culture for Coxiella burnetti or anti-phase 1 IgG antibody titer greater than 1:800
Evidence of endocardial involvement
Echocardiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE
[paravalvular abscess]; TTE as first test in other patients), defined as follows:
Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative
anatomic explanation; or
Abscess; or
New partial dehiscence of prosthetic valve
New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient)
Minor criteria
Predisposition, predisposing heart condition or injection drug use
Fever, temperature greater than 38°C
Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway’s
lesions
Immunologic phenomena; glomerulonephritis, Osler’s nodes. Roth’s spots, and rheumatoid factor
Microbiological evidence: positive blood culture but does not meet a major criterion,† or serological evidence of active infection with organism consistent with IE
Echocardiographic minor criteria eliminated
*Modifications are shown in bold type.
†Excludes single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis. Reprinted with permission from Li JS, Sexton
DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633– 8.722
IE indicates infective endocarditis; TEE, transesophageal echocardiography; and TTE, transthoracic echocardiography.
4.3. Endocarditis in HIV-Seropositive Patients
Endocarditis in patients who are HIV (human immunodeficiency virus) seropositive usually occurs as a complication of
injection drug use or long-term indwelling central catheters.
Table 23.
S. aureus is the most frequent pathogen. When endocarditis is
not related to intravenous drug use, right- and left-sided
valves are equally involved. Intravenous drug use is the most
common cause of tricuspid valve endocarditis. Endocarditis-
Definition of Infective Endocarditis According to the Proposed Modified Duke Criteria*
Definite infective endocarditis
Pathological criteria
(1) Microorganisms demonstrated by culture or histological examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or
(2) Pathological lesions; vegetation, or intracardiac abscess confirmed by histological examination showing active endocarditis
Clinical criteria
(1) 2 major criteria, or
(2) 1 major criterion and 3 minor criteria; or
(3) 5 minor criteria
Possible infective endocarditis
(1) 1 major criterion and 1 minor criterion; or
(2) 3 minor criteria
Rejected
(1) Firm alternate diagnosis explaining evidence of infective endocarditis; or
(2) Resolution of infective endocarditis syndrome with antibiotic therapy for less than 4 days; or
(3) No pathological evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for less than 4 days; or
(4) Does not meet criteria for possible infective endocarditis, as noted above
*Modifications are shown in bold type. Reprinted with permission from Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis
of infective endocarditis. Clin Infect Dis 2000;30:633– 8.722
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Table 24. Therapy of Native Valve Endocarditis Caused by Highly Penicillin-Susceptible Viridans Group Streptococci and
Streptococcus bovis
Duration,
wk
Regimen
Dosage and Route*
Aqueous crystalline
penicillin G
sodium
12–18 million U per 24 h IV either continuously or in 4 or
6 equally divided doses
4
2 g per 24 h IV/IM in 1 dose
4
Comments
Preferred in most patients greater than 65 y of age
or patients with impairment of 8th cranial nerve
function or renal function
or
Ceftriaxone sodium
Pediatric dose†: penicillin 200 000 U per kg per 24 h IV
in 4–6 equally divided doses; ceftriaxone 100 mg per
kg per 24 h IV/IM in 1 dose
Aqueous crystalline
penicillin G
sodium
12–18 million U per 24 h IV either continuously or in 6
equally divided doses
2
2 g per 24 h IV/IM in 1 dose
2
3 mg per kg per 24 h IV/IM in 1 dose
2
Pediatric dose: penicillin 200 000 U per kg per 24 h IV in
4–6 equally divided doses; ceftriaxone 100 mg per kg
per 24 h IV/IM in 1 dose; gentamicin 3 mg per kg per
24 h
2
Two-week regimen not intended for patients with
known cardiac or extracardiac abscess or for those
with creatinine clearance of less than 20 ml per
min, impaired 8th cranial nerve function, or
Abiotrophia, Granulicatella, or Gemella spp
infection. Gentamicin dosage should be adjusted to
achieve peak serum concentration of 3–4 mcg per
ml and trough serum concentration of less than 1
␮g per ml when 3 divided doses are used;
nomogram used for single daily dosing.
or
Ceftriaxone sodium
plus
Gentamicin sulfate‡
IV/IM in 1 dose or 3 equally divided doses§
Vancomycin
hydrochloride储
30 mg per kg per 24 h IV in 2 equally divided doses not
to exceed 2 g per 24 h unless concentrations in
serum are inappropriately low
Pediatric dose: 40 mg per kg per 24 h IV in 2–3 equally
divided doses
4
Vancomycin therapy recommended only for patients
unable to tolerate penicillin or ceftriaxone;
vancomycin dosage should be adjusted to obtain
peak (1 h after infusion completed) serum
concentration of 30–45 ␮g per ml and a trough
concentration range of 10–15 ␮g per ml
Minimum inhibitory concentration less than or equal to 0.12 ␮g per ml.
*Dosages recommended are for patients with normal renal function.
†Pediatric dose should not exceed that of a normal adult.
‡Other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy.
§Data for once-daily dosing of aminoglycosides for children exist, but no data for treatment of infective endocarditis exist.
储Vancomycin dosages should be infused during course of at least 1 h to reduce risk of histamine-release “red man” syndrome.
Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement
for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the
Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434.723
IM indicates intramuscular; and IV, intravenous.
related mortality in patients with acquired immune deficiency
syndrome (AIDS) exceeds that of HIV-positive patients
without AIDS. Thus, it is recommended that endocarditis in
patients with AIDS be treated with maximum-duration antibiotic regimens.723
4.4. Indications for Echocardiography in
Suspected or Known Endocarditis
Echocardiography is useful for the detection and characterization of the hemodynamic and pathological consequences of infection. These consequences include valvular
vegetations; valvular regurgitation; ventricular dysfunction; and associated lesions such as abscesses, shunts, and
ruptured chordae.727 The indications for transthoracic and
transesophageal echocardiography are discussed in the
“ACC/AHA/ASE 2004 Guidelines for the Clinical Application of Echocardiography”2 and the 2005 AHA endocarditis guidelines.723 Transesophageal imaging is more sensitive in detecting vegetations than transthoracic
imaging,718,723,728 particularly in patients with prosthetic
valves, and in determining the presence and severity of
important complications such as abscesses and perforations. In patients with prosthetic valves, it is reasonable to
proceed directly to transesophageal imaging as the firstline diagnostic test when endocarditis is suspected. Echocardiography can be useful in the case of culture-negative
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October 7, 2008
Table 25. Therapy of Native Valve Endocarditis Caused by Strains of Viridans Group Streptococci and Streptococcus bovis Relatively
Resistant to Penicillin
Regimen
Aqueous crystalline
penicillin G
sodium
Dosage* and Route
Duration,
wk
Comments
24 million U per 24 h IV either continuously or in 4 to 6
equally divided doses
4
Patients with endocarditis caused by penicillin-resistant
(MIC greater than 0.5 ␮g per ml) strains should be
treated with regimen recommended for enterococcal
endocarditis
2 g per 24 h IV/IM in 1 dose
4
Recommended for enterococcal endocarditis (see Table
26)723
3 mg per kg per 24 h IV/IM in 1 dose
2
or
Ceftriaxone sodium
plus
Gentamicin sulfate†
Pediatric dose‡: penicillin 300 000 U per 24 h IV in 4 to
6 equally divided doses; ceftriaxone 100 mg per kg per
24 h IV/IM in 1 dose; gentamicin 3 mg per kg per 24 h
IV/IM in 1 dose or 3 equally divided doses
Vancomycin
hydrochloride‡
30 mg per kg per 24 h IV in 2 equally divided doses not
to exceed 2 g per 24 h, unless serum concentrations
are inappropriately low
4
Vancomycin§ therapy is recommended only for
patients unable to tolerate penicillin or ceftriaxone
therapy
Pediatric dose: 40 mg per kg per 24 h in 2 or 3 equally
divided doses
Minimum inhibitory concentration (MIC) greater than 0.12 ␮g per ml to less than or equal to 0.5 ␮g per ml.
*Dosages recommended are for patients with normal renal function.
†See Table 24 for appropriate dosage of gentamicin.
‡Pediatric dose should not exceed that of a normal adult.
§See Table 24 for appropriate dosage of vancomycin.
Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement
for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the
Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434.723
IM indicates intramuscular; IV, intravenous; and MIC, minimum inhibitory concentration.
endocarditis729 or the diagnosis of a persistent bacteremia
the source of which remains unidentified after appropriate
evaluation.2
4.4.1. Transthoracic Echocardiography in Endocarditis
Class I
1. Transthoracic echocardiography to detect valvular
vegetations with or without positive blood cultures is
recommended for the diagnosis of infective endocarditis. (Level of Evidence: B)
2. Transthoracic echocardiography is recommended to
characterize the hemodynamic severity of valvular lesions in
known infective endocarditis. (Level of Evidence: B)
3. Transthoracic echocardiography is recommended for
assessment of complications of infective endocarditis
(e.g., abscesses, perforation, and shunts). (Level of
Evidence: B)
4. Transthoracic echocardiography is recommended for
reassessment of high-risk patients (e.g., those with a
virulent organism, clinical deterioration, persistent or
recurrent fever, new murmur, or persistent bacteremia). (Level of Evidence: C)
Class IIa
1. Transthoracic echocardiography is reasonable to diagnose infective endocarditis of a prosthetic valve in the
presence of persistent fever without bacteremia or a
new murmur. (Level of Evidence: C)
Class IIb
1. Transthoracic echocardiography may be considered
for the re-evaluation of prosthetic valve endocarditis
during antibiotic therapy in the absence of clinical
deterioration. (Level of Evidence: C)
Class III
1. Transthoracic echocardiography is not indicated to reevaluate uncomplicated (including no regurgitation on baseline echocardiogram) native valve endocarditis during antibiotic treatment in the absence of clinical deterioration, new
physical findings or persistent fever. (Level of Evidence: C)
4.4.2. Transesophageal Echocardiography in Endocarditis
Class I
1. Transesophageal echocardiography is recommended to
assess the severity of valvular lesions in symptomatic
patients with infective endocarditis, if transthoracic echocardiography is nondiagnostic. (Level of Evidence: C)
2. Transesophageal echocardiography is recommended to
diagnose infective endocarditis in patients with valvular
heart disease and positive blood cultures, if transthoracic
echocardiography is nondiagnostic. (Level of Evidence: C)
3. Transesophageal echocardiography is recommended to
diagnose complications of infective endocarditis with
potential impact on prognosis and management (e.g.,
abscesses, perforation, and shunts). (Level of Evidence: C)
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Table 26. Therapy for Native Valve or Prosthetic Valve Enterococcal Endocarditis Caused by Strains Susceptible to Penicillin,
Gentamicin, and Vancomycin
Regimen
Ampicillin sodium
Duration,
wk
Dosage* and Route
Comments
12 g per 24 h IV in 6 equally divided doses
4 to 6
Native valve: 4-wk therapy recommended for
patients with symptoms of illness less than or
equal to 3 mo; 6-wk therapy recommended for
patients with symptoms greater than 3 mo
18–30 million U per 24 h IV either continuously or in 6
equally divided doses
4 to 6
Prosthetic valve or other prosthetic cardiac material:
minimum of 6-wk therapy recommended
3 mg per kg per 24 h IV/IM in 3 equally divided doses
4 to 6
or
Aqueous crystalline
penicillin G sodium
plus
Gentamicin sulfate†
Pediatric dose‡: ampicillin 300 mg per kg per 24 h IV in 4 to
6 equally divided doses; penicillin 300 000 U per kg per
24 h IV in 4 to 6 equally divided doses; gentamicin 3 mg
per kg per 24 h IV/IM in 3 equally divided doses
Vancomycin
hydrochloride§
30 mg per kg per 24 IV in 2 equally divided doses
6
Vancomycin therapy is recommended only for
patients unable to tolerate penicillin or ampicillin
3 mg per kg per 24 h IV/IM in 3 equally divided doses
Pediatric dose: vancomycin 40 mg per kg per 24 h
IV in 2 or 3 equally divided doses; gentamicin 3 mg per kg
per 24 h IV/IM in 3 equally divided doses
6
6 wk of vancomycin therapy recommended because
of decreased activity against enterococci
plus
Gentamicin sulfate
*Dosages recommended are for patients with normal renal function.
†Dosage of gentamicin should be adjusted to achieve peak serum concentration of 3 to 4 ␮g per ml and a trough concentration of less than 1 ␮g per ml. Patients
with a creatinine clearance of less than 50 ml per min should be treated in consultation with an infectious diseases specialist.
‡Pediatric dose should not exceed that of a normal adult.
§See Table 24 for appropriate dosing of vancomycin.
Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement
for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the
Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434.723 See full
document for treatment regimens of resistant organisms.
IM indicates intramuscular; IV, intravenous.
4. Transesophageal echocardiography is recommended
as first-line diagnostic study to diagnose prosthetic
valve endocarditis and assess for complications. (Level
of Evidence: C)
5. Transesophageal echocardiography is recommended
for preoperative evaluation in patients with known
infective endocarditis, unless the need for surgery is
evident on transthoracic imaging and unless preoperative imaging will delay surgery in urgent cases. (Level
of Evidence: C)
6. Intraoperative transesophageal echocardiography is
recommended for patients undergoing valve surgery
for infective endocarditis. (Level of Evidence: C)
4.5. Outpatient Treatment
Patients with penicillin-susceptible S. viridans endocarditis
who are hemodynamically stable, compliant, and capable of
managing the technical aspects of outpatient therapy may be
candidates for a single daily-dose regimen of ceftriaxone.723
Clinical reports suggest that right-sided endocarditis caused
by S. aureus in intravenous drug users may be amenable to a
short 2-week course of therapy.730,731 Monotherapy with
ceftriaxone or combination therapy with an aminoglycoside
has been tried as an outpatient therapeutic option732; however,
more data are needed to determine with more certainty
whether such outpatient regimens have therapeutic effectiveness equivalent to the established 4- to 6-week regimens.
Class IIa
1. Transesophageal echocardiography is reasonable to
diagnose possible infective endocarditis in patients
with persistent staphylococcal bacteremia without a
known source. (Level of Evidence: C)
Class IIb
1. Transesophageal echocardiography might be considered to detect infective endocarditis in patients with
nosocomial staphylococcal bacteremia. (Level of Evidence: C)
4.6. Indications for Surgery in Patients With
Acute Infective Endocarditis
Surgery is indicated in patients with life-threatening congestive heart failure or cardiogenic shock due to surgically
treatable valvular heart disease with or without proven
infective endocarditis if the patient has reasonable prospects
of recovery with satisfactory quality of life after the operation.615,723,733–757 Surgery should not be delayed in the setting
of acute infective endocarditis when congestive heart failure
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Table 27.
October 7, 2008
Therapy for Endocarditis Caused by Staphylococci in the Absence of Prosthetic Materials
Regimen
Dosage* and Route
Duration
Comments
Oxacillin-susceptible strains
Nafcillin or oxacillin†
12 g per 24 h IV in 4–6 equally divided doses
6 wk
For complicated right-sided IE and for left-sided IE;
for uncomplicated right-sided IE, 2 wk (see full
text)
3 mg per kg per 24 h IV/IM in 2 or 3 equally
divided doses
3–5 d
Clinical benefit of aminoglycosides has not been
established
with
Optional addition of
gentamicin sulfate‡
Pediatric dose§: Nafcillin or oxacillin 200 mg
per kg per 24 h IV in 4–6 equally divided
doses; gentamicin 3 mg per kg per 24 h IV/
IM in 3 equally divided doses
For penicillin-allergic
(nonanaphylactoid type)
patients:
Cefazolin
Consider skin testing for oxacillin-susceptible
staphylococci and questionable history of
immediate-type hypersensitivity to penicillin
6 g per 24 h IV in 3 equally divided doses
6 wk
Cephalosporins should be avoided in patients with
anaphylactoid-type hypersensitivity to beta lactams;
vancomycin should be used in these cases§
3 mg per kg per 24 h IV/IM in 2 or 3 equally
divided doses
3–5 d
Clinical benefit of aminoglycosides has not been
established
6 wk
Adjust vancomycin dosage to achieve 1-h serum
concentration of 30–45 ␮g per ml and trough
concentration of 10–15 ␮g per ml
with
Optional addition of
gentamicin sulfate
Pediatric dose: cefazolin 100 mg per kg per
24 h IV in 3 equally divided doses;
gentamicin 3 mg per kg per 24 h IV/IM in 3
equally divided doses
Oxacillin-resilient strains
Vancomycin储
30 mg per kg per 24 h IV in 2 equally divided
doses
*Dosages recommended are for patients with normal renal function.
†Penicillin G 24 million U per 24 h IV in 4 to 6 equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin susceptible (minimum inhibitory
concentration less than or equal to 0.1 ␮g per ml) and dose does not produce beta lactamase.
‡Gentamicin should be administered in close temporal proximity to vancomycin, nafcillin, or oxacillin dosing.
§Pediatric dose should not exceed that of a normal adult.
储For specific dosing adjustment and issues concerning vancomycin, see Table 24 footnotes.
Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement
for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the
Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434.723
IE indicates infective endocarditis; IM, intramuscular; and IV, intravenous.
intervenes. Surgery is not indicated if complications (severe
embolic cerebral damage) or comorbid conditions make the
prospect of recovery remote.
The indications for surgery for infective endocarditis in
patients with stable hemodynamics are less clear. Consultation with a cardiovascular surgeon is recommended in a
patient with complicated endocarditis so that the surgical
team is aware of the patient who may suddenly need surgery.
Surgery is recommended in patients with annular or aortic
abscesses, heart block, recurrent emboli on appropriate antibiotic therapy, infections resistant to antibiotic therapy, and
fungal endocarditis. It is recognized that the presence of
valvular vegetations poses a threat of embolic events. Prosthetic valve endocarditis and native valve endocarditis caused
by S. aureus are almost always surgical diseases. Early
surgery in MV endocarditis caused by virulent organisms
(such as S. aureus or fungi) may make repair possible.
Echocardiography, especially with transesophageal imaging,
identifies vegetations and provides size estimation in many
instances. Patients with a vegetation diameter greater than 10
mm have a significantly higher incidence of embolization
than those with a vegetation diameter less than or equal to 10
mm,718 and this risk appears to be higher in patients with MV
endocarditis than in those with aortic valve endocarditis.
However, surgery on the basis of vegetation size alone is
controversial.
Patients with prosthetic valves who receive warfarin anticoagulation and develop endocarditis should have their warfarin discontinued and replaced with heparin. This recommendation is less related to the possibility of hemorrhagic
complications of endocarditis758 than the possibility of urgent
surgery. If surgery is required, the effects of warfarin will
have dissipated, and heparin can easily be reversed. Likewise,
aspirin, if part of the medical regimen, should also be
discontinued. If neurological symptoms develop, anticoagulation should be discontinued until an intracranial hemorrhagic event is excluded by magnetic resonance imaging or
computed tomographic scanning.
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Table 28.
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Therapy for Prosthetic Valve Endocarditis Caused by Staphylococci
Regimen
Duration,
wk
Dosage* and Route
Comments
Oxacillin-susceptible strains
Nafcillin or oxacillin
12 g per 24 h IV in 6 equally divided doses
At least 6
900 mg per 24 h IV/PO in 3 equally divided doses
At least 6
Penicillin G 24 million U per 24 h IV in 4 to 6 equally
divided doses may be used in place of nafcillin or
oxacillin if strain is penicillin susceptible (minimum
inhibitory concentration less than or equal to 0.1
mcg per ml) and does not produce ␤-lactamase;
vancomycin should be used in patients with
immediate-type hypersensitivity reactions to ␤lactam antibiotics (see Table 24 for dosing
guidelines); cefazolin may be substituted for nafcillin
or oxacillin in patients with non-immediate-type
hypersensitivity reactions to penicillins
plus
Rifampin
plus
Gentamicin†
3 mg per kg per 24 h IV/IM in 2 or 3 equally divided
doses
Pediatric dose‡: nafcillin or oxacillin 200 mg per kg
per 24 h IV in 4 to 6 equally divided doses;
rifampin 20 mg per kg per 24 h IV/PO in 3 equally
divided doses; gentamicin 3 mg per kg per 24 h
IV/IM in 2 equally divided doses
Oxacillin-resistant strains
Vancomycin
30 mg per kg per 24 h in 2 equally divided doses
At least 6
900 mg per 24 h IV/PO in 3 equally divided doses
At least 6
Adjust vancomycin to achieve 1-h serum concentration
of 30 to 45 ␮g per ml and trough concentration of
10 to 15 ␮g per ml
plus
Rifampin
plus
Gentamicin
3 mg per kg per 24 h IV/IM in 2 or 3 equally divided
doses
Pediatric dose: vancomycin 40 mg per kg per 24 h
IV in 2 or 3 equally divided doses; rifampin 20 mg
per kg per 24 h IV/PO in 3 equally divided doses
(up to adult dose); gentamicin 3 mg per kg per
24 h IV or IM in 3 equally divided doses
*Dosages recommended are for patients with normal renal function.
†Gentamicin should be administered in close proximity to vancomycin, nafcillin, or oxacillin dosing.
‡Pediatric dose should not exceed that of a normal adult.
Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement
for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the
Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434.723
IM indicates intramuscular; IV, intravenous; and PO, by mouth.
4.6.1. Surgery for Native Valve Endocarditis
Class I
1. Surgery of the native valve is indicated in patients with
acute infective endocarditis who present with valve
stenosis or regurgitation resulting in heart failure.
(Level of Evidence: B)
2. Surgery of the native valve is indicated in patients with
acute infective endocarditis who present with AR or MR
with hemodynamic evidence of elevated LV end-diastolic
or left atrial pressures (e.g., premature closure of MV
with AR, rapid decelerating MR signal by continuous-
wave Doppler (v-wave cutoff sign), or moderate or severe
pulmonary hypertension). (Level of Evidence: B)
3. Surgery of the native valve is indicated in patients with
infective endocarditis caused by fungal or other highly
resistant organisms. (Level of Evidence: B)
4. Surgery of the native valve is indicated in patients with
infective endocarditis complicated by heart block, annular or aortic abscess, or destructive penetrating
lesions (e.g., sinus of Valsalva to right atrium, right
ventricle, or left atrium fistula; mitral leaflet perforation with aortic valve endocarditis; or infection in
annulus fibrosa). (Level of Evidence: B)
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Table 29.
October 7, 2008
Therapy for Both Native and Prosthetic Valve Endocarditis Caused by HACEK* Microorganisms
Regimen
Ceftriaxone sodium
Dosage and Route
Duration,
wk
2 g per 24 h IV/IM in 1 dose†
4
12 g per 24 IV in 4 equally divided doses
4
1000 mg per 24 h PO or 800 mg per 24 h IV
in 2 equally divided doses
Pediatric dose储: Ceftriaxone 100 mg per kg
per 24 h IV/IM once daily; ampicillinsulbactam 300 mg per kg per 24 h IV
divided into 4 or 6 equally divided doses;
ciprofloxacin 20 to 30 mg per kg per 24 h
IV/PO in 2 equally divided doses
4
Comments
Cefotaxime or another third- or fourth-generation cephalosporin
may be substituted
or
Ampicillin-sulbactam‡
or
Ciprofloxacin‡§
Fluoroquinolone therapy recommended only for patients unable
to tolerate cephalosporin and ampicillin therapy;
levofloxacin, gatifloxacin, or moxifloxacin may be
substituted; fluoroquinolones generally not recommended for
patients less than 18 y old
Prosthetic valve: patients with endocarditis involving prosthetic
cardiac valve or other prosthetic cardiac material should be
treated for 6 wk
*Haemophilus parainfluenzae, Haphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae.
†Patients should be informed that intramuscular injection of ceftriaxone is painful.
‡Dosage recommended for patients with normal renal function.
§Fluoroquinolones are highly active in vitro against HACEK microorganisms. Published data on use of fluoroquinolone therapy for endocarditis caused by HACEK are minimal.
储Pediatric dose should not exceed that of a normal adult.
Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement
for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the
Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434.723
IM indicates intramuscular; IV, intravenous; and PO, by mouth.
Class IIa
1. Surgery of the native valve is reasonable in patients
with infective endocarditis who present with recurrent
emboli and persistent vegetations despite appropriate
antibiotic therapy. (Level of Evidence: C)
Class IIb
1. Surgery of the native valve may be considered in
patients with infective endocarditis who present with
mobile vegetations in excess of 10 mm with or without
emboli. (Level of Evidence: C)
Patients with left-sided native valve endocarditis complicated by
congestive heart failure, systemic embolization to vital organs,
or presence of a large vegetation on echocardiography have poor
outcomes on medical treatment alone. A large cohort study using
a multivariate model reported that valve surgery was associated
with improved 6-month survival.759 An additional benefit of
early surgery is likely to include successful valve repair as an
outcome, especially for the MV. When at all possible, MV repair
should be performed instead of MV replacement in the setting of
active infection because of the risk of infection of prosthetic
materials.760 –762 Aortic valves may often be repaired as well if
there are leaflet perforations, and this is preferable to AVR for
the same reasons.
4.6.2. Surgery for Prosthetic Valve Endocarditis
Class I
1. Consultation with a cardiac surgeon is indicated for
patients with infective endocarditis of a prosthetic
valve. (Level of Evidence: C)
2. Surgery is indicated for patients with infective endocarditis of a prosthetic valve who present with heart
failure. (Level of Evidence: B)
3. Surgery is indicated for patients with infective endocarditis of a prosthetic valve who present with dehiscence evidenced by cine fluoroscopy or echocardiography. (Level of Evidence: B)
4. Surgery is indicated for patients with infective endocarditis of a prosthetic valve who present with evidence
of increasing obstruction or worsening regurgitation.
(Level of Evidence: C)
5. Surgery is indicated for patients with infective endocarditis of a prosthetic valve who present with complications (e.g., abscess formation). (Level of Evidence: C)
Class IIa
1. Surgery is reasonable for patients with infective endocarditis of a prosthetic valve who present with evidence of
persistent bacteremia or recurrent emboli despite appropriate antibiotic treatment. (Level of Evidence: C)
2. Surgery is reasonable for patients with infective endocarditis of a prosthetic valve who present with relapsing infection. (Level of Evidence: C)
Class III
1. Routine surgery is not indicated for patients with
uncomplicated infective endocarditis of a prosthetic
valve caused by first infection with a sensitive organism. (Level of Evidence: C)
5. Management of Valvular Disease in
Pregnancy
5.1. Physiological Changes of Pregnancy
The evaluation and management of valvular heart disease in
the pregnant patient requires an understanding of the normal
physiological changes associated with gestation, labor, delivery, and the early postpartum period. On average, there is a
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Bonow et al
Table 30.
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
e597
Therapy for Culture-Negative Endocarditis Including Bartonella Endocarditis
Regimen
Native valve
Ampicillin-sulbactam
plus
Gentamicin sulfate†
Vancomycin‡
plus
Gentamicin sulfate
plus
Ciprofloxacin
Prosthetic valve (early—less
than or equal to 1 y)
Vancomycin
plus
Gentamicin sulfate
plus
Cefepime
plus
Rifampin
Prosthetic valve (late—
greater than 1 y)
Suspected Bartonella,
culture negative
Ceftriaxone sodium
plus
Gentamicin sulfate
with/without
Doxycycline
Documented Bartonella,
culture positive
Doxycycline
plus
Gentamicin sulfate
Dosage* and Route
Duration,
wk
12 g per 24 h IV in 4 equally divided doses
4–6
3 mg per kg per 24 h IV/IM in 3 equally divided doses
30 mg per kg per 24 h IV in 2 equally divided doses
4–6
4–6
3 mg per kg per 24 h IV/IM in 3 equally divided doses
4–6
1000 mg per 24 h PO or 800 mg per 24 h IV in 2 equally divided
doses
Pediatric dose§: ampicillin-sulbactam 300 mg per kg per 24 h IV
in 4–6 equally divided doses; gentamicin 3 mg per kg per 24 h
IV/IM in 3 equally divided doses; vancomycin 40 mg per kg per
24 h in 2 or 3 equally divided doses; ciprofloxacin 20–30 mg
per kg per 24 h IV/PO in 2 equally divided doses
4–6
30 mg per kg per 24 h IV in 2 equally divided doses
6
3 mg per kg per 24 h IV/IM in 3 equally divided doses
2
6 g per 24 h IV in 3 equally divided doses
6
900 mg per 24 h PO/IV in 3 equally divided doses
Pediatric dose: vancomycin 40 mg per kg per 24 h IV in 2 or 3
equally divided doses; gentamicin 3 mg per kg per 24 h IV/IM
in 3 equally divided doses; cefepime 150 mg per kg per 24 h
IV in 3 equally divided doses; rifampin 20 mg per kg per 24 h
PO/IV in 3 equally divided doses
6
Comments
Patients with culture-negative endocarditis
should be treated with consultation with
an infectious diseases specialist
Vancomycin recommended only for patients
unable to tolerate penicillins
6
Same regimens as listed above for native
valve endocarditis
2 g per 24 h IV/IM in 1 dose
6
Patients with Bartonella endocarditis should
be treated in consultation with an
infectious diseases specialist
3 mg per kg per 24 h IV/IM in 3 equally divided doses
2
200 mg per kg per 24 h IV/PO in 2 equally divided doses
6
200 mg per 24 h IV or PO in 2 equally divided doses
6
3 mg per kg per 24 h IV/IM in 3 equally divided doses
Pediatric dose: ceftriaxone 100 mg per kg per 24 h IV/IM once
daily; gentamicin 3 mg per kg per 24 h IV/IM in 3 equally
divided doses; doxycycline 2–4 mg per kg per 24 h IV/PO in 2
equally divided doses; rifampin 20 mg per kg per 24 h PO/IV in
2 equally divided doses
2
If gentamicin cannot be given, then replace
with rifampin, 600 mg per 24 h PO/IV in
2 equally divided doses
*Dosages recommended are for patients with normal renal function.
†See Table 24 for appropriate dosing of gentamicin.
‡See Table 24 for appropriate dosing of vancomycin.
§Pediatric dose should not exceed that of a normal adult.
Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement
for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the
Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434.723
IM indicates intramuscular; IV, intravenous; and PO, by mouth.
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October 7, 2008
50% increase in circulating blood volume during pregnancy
that is accompanied by a commensurate increase in cardiac
output that usually peaks between the midportion of the
second and third trimesters. The augmented cardiac output
derives from an increase in the stroke volume, although there
is also a smaller increase in heart rate, averaging 10 to 20
beats per minute. Because of the effects of uterine circulation
and endogenous hormones, systemic vascular resistance falls
with a disproportionately greater lowering of diastolic blood
pressure and a wide pulse pressure. Inferior vena caval
obstruction from a gravid uterus in the supine position can
result in an abrupt decrease in cardiac preload, which leads to
hypotension with weakness and lightheadedness. These
symptoms resolve quickly with a change in position.763
There is a further abrupt increase in cardiac output during
labor and delivery related in part to the associated anxiety and
pain. Uterine contractions can lead to marked increases in
both systolic and diastolic blood pressure. After delivery,
there is an initial surge in preload related to the autotransfusion of uterine blood into the systemic circulation and to
caval decompression.763
Pregnancy is also associated with a hypercoagulable state
due to relative decreases in protein S activity, stasis, and
venous hypertension.764 Estrogens can interfere with collagen
deposition within the media of the medium and large muscular arteries. Circulating elastase can break up the elastic
lamellae and weaken the aortic media during pregnancy.
Weakening of the vascular wall may in turn predispose to
dissection with or without an underlying connective tissue
disorder.765 Relaxin, an insulin-like growth factor hormone, is
detectable in serum during pregnancy and causes a decrease
in collagen synthesis and may predispose to aortic dissection
during pregnancy.766
5.2. Physical Examination
The physical examination of the normal parturient is notable
for a slightly fast resting heart rate, bounding pulses, a
widened pulse pressure with a low normal peak systolic
pressure, and warm extremities. Venous pressure is usually at
or near the upper limits for nonpregnant women but rarely in
a clearly abnormal range. The thyroid gland may be enlarged
in the absence of clinical hyperthyroidism. Depending on the
stage of pregnancy, the lung volumes may be low because of
the raised diaphragms. The precordial impulse is hyperkinetic, and the first heart sound may be louder than normal,
with prominent splitting. The second heart sound is usually
physiologically split but may also widen and appear fixed
during the later stages of pregnancy. Third heart sounds are
present in most patients. A soft grade 1 to 2 midsystolic
murmur that is best heard along the mid to upper left sternal
edge is a frequent finding.26 A continuous murmur, which
reflects either a venous hum or a mammary souffle, may
sometimes be heard during auscultation. The cervical venous
hum is best appreciated in the right supraclavicular fossa and
can be obliterated by movement of the chin toward the
stethoscope or digital pressure over the ipsilateral jugular
vein. The mammary souffle is a systolic or continuous sound
over the engorged breast that can usually be obliterated with
firm pressure applied to the diaphragm of the stethoscope. It
Table 31. Valvular Heart Lesions Associated With High
Maternal and/or Fetal Risk During Pregnancy
Severe AS with or without symptoms
AR with NYHA functional class III–IV symptoms
MS with NYHA functional class II–IV symptoms
MR with NYHA functional class III–IV symptoms
Aortic and/or mitral valve disease resulting in severe pulmonary
hypertension (pulmonary pressure greater than 75% of systemic
pressures)
6. Aortic and/or mitral valve disease with severe LV dysfunction (EF less
than 0.40)
7. Mechanical prosthetic valve requiring anticoagulation
8. Marfan syndrome with or without AR
1.
2.
3.
4.
5.
AR indicates aortic regurgitation; AS, aortic stenosis; EF, ejection fraction;
LV, left ventricular; MR, mitral regurgitation; MS, mitral stenosis; and NYHA,
New York Heart Association.
is heard in the supine position and attenuates or disappears
when standing. It is appreciated in the late stages of pregnancy or early in the puerperium. Diastolic heart murmurs are
unusual. The increased blood volume and enhanced cardiac
output associated with normal pregnancy can accentuate the
murmurs associated with stenotic heart valve lesions (e.g.,
MS and AS). On the other hand, murmurs of AR, MR, and
ventricular septal defect can actually attenuate or become
inaudible as systemic vascular resistance is lowered.767
5.3. Echocardiography
Normal pregnancy is accompanied by echocardiographic
evidence of mild ventricular chamber enlargement. Pulmonic
and tricuspid valvular regurgitation, as assessed by Doppler
interrogation, is the rule rather than the exception.768 Most
women will demonstrate Doppler evidence of “physiological” MR in the absence of structural valve disease. Atrioventricular valve regurgitation may result from the annular
dilatation that accompanies ventricular enlargement. Appreciation of these echocardiographic and Doppler findings in
normal individuals is an important foundation for the noninvasive evaluation of subjects with suspected valvular disease.
The use of ultrasound during pregnancy poses no risk to the
mother or fetus.
5.4. General Management Guidelines
Clinical experience has shown that there are several cardiac
conditions in which the physiological changes of pregnancy
are poorly tolerated. For some conditions, such as cyanotic
heart disease, Eisenmenger syndrome, or severe pulmonary
hypertension, pregnancy should be discouraged. Valvular
heart lesions associated with high maternal and fetal risk
during pregnancy are listed in Table 31. Lesions associated
with low risk during pregnancy are listed in Table 32.
Reimold and Rutherford769 and Elkayam and Bitar770,771
have published excellent reviews for the clinical practitioner
involved in managing pregnant patients who have either
valvular or prosthetic heart disease. They delineate the
increased risk of adverse maternal, fetal, and neonatal outcomes on the basis of valvular abnormality and the NYHA
functional class. Additionally, Siu et al. have identified
predictors of adverse maternal and fetal outcomes in a
heterogeneous group of Canadian women with congenital or
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Bonow et al
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
Table 32. Valvular Heart Lesions Associated With Low
Maternal and Fetal Risk During Pregnancy
1. Asymptomatic AS with low mean gradient (less than 25 mm Hg and
aortic valve area greater than 1.5 cm2) in presence of normal LV
systolic function (EF greater than 0.50)
2. NYHA functional class I or II AR with normal LV systolic function
3. NYHA functional class I or II MR with normal LV systolic function
4. MVP with no MR or with mild to moderate MR with normal LV systolic
function
5. Mild MS (MVA greater than 1.5 cm2, gradient less than 5 mm Hg)
without severe pulmonary hypertension
6. Mild to moderate pulmonary valve stenosis
AR indicates aortic regurgitation; AS, aortic stenosis; EF, ejection fraction;
LV, left ventricular; MR, mitral regurgitation; MS, mitral stenosis; MVA, mitral
valve area; MVP, mitral valve prolapse; and NYHA, New York Heart Association.
acquired heart disease.772,773 Abnormal functional capacity
(NYHA functional class II or higher) and left-sided heart
obstruction were predictors of neonatal complications that
included premature birth, intrauterine growth retardation,
respiratory distress syndrome, intraventricular hemorrhage,
and death. However, outcomes data are limited for pregnant
patients with valvular heart disease, except for those with
MS.769,770
Individual counseling usually requires a multidisciplinary
approach and should include information regarding contraception, maternal and fetal risks of pregnancy, and expected
long-term outcomes. However, many patients with valvular
heart disease can be successfully managed throughout pregnancy and during labor and delivery with conservative
medical measures designed to optimize intravascular volume
and systemic loading conditions.
Simple interventions such as bed rest and avoidance of the
supine position should not be overlooked. Whenever possible, symptomatic or severe valvular lesions should be addressed and rectified before conception and pregnancy. Contemporaneous management with a dedicated obstetric team
accustomed to working with high-risk patients is encouraged.
Drugs should generally be avoided whenever possible (Table
33).763
5.5. Specific Lesions
5.5.1. Mitral Stenosis
Young pregnant women with a previous history of acute
rheumatic fever and carditis should continue to receive
penicillin prophylaxis as indicated in the nonpregnant state.
Patients with mild to moderate MS can almost always be
managed with judicious use of diuretics and beta blockade.
Diuretics are given to relieve pulmonary and excess systemic
venous congestion, but care must be taken to avoid vigorous
volume depletion to protect against uteroplacental hypoperfusion. Beta blockers are chiefly indicated to treat or prevent
tachycardia to optimize diastolic filling. Although the nonselective beta blocker propranolol has been in use for decades,
some authorities recommend a cardioselective beta blocker
such as metoprolol or atenolol to prevent the potential
deleterious effects of epinephrine blockade on myometrial
activity.
e599
Patients with severe MS who are symptomatic before
conception will not predictably tolerate the hemodynamic
burden of pregnancy and should be considered for percutaneous balloon mitral valvotomy before conception, provided
the valve is anatomically suitable. Patients with severe MS who
develop NYHA functional class III–IV symptoms during pregnancy should undergo percutaneous balloon valvotomy.774
For the rare patients with MS who fail medical management during pregnancy with repetitive or persistent heart
failure, there is now a nearly 10-year experience with balloon
mitral valvotomy, either with very limited fluoroscopy (less
than 1 to 2 minutes’ exposure with both pelvic and abdominal
shielding) or echocardiographic guidance. The reported results with mitral balloon valvotomy have been excellent, with
few maternal or fetal complications, although caution is advised
in interpreting outcomes from individual centers reporting relatively few patients.775–784 Percutaneous mitral balloon valvotomy should only be performed in experienced centers and only
after aggressive medical measures have been exhausted. In
developing countries, there is a long history of successful
surgical closed commissurotomy for pregnant women.785
5.5.2. Mitral Regurgitation
MVP is the most common cause of MR in pregnant women.
The physical findings pertinent to MVP may be obscured or
varied by the physiological changes of pregnancy, especially
the increased blood volume and reduced systemic vascular
resistance. Associated MR can usually be managed medically, although on rare occasions, MV surgery is required
because of ruptured chordae and acute, severe worsening of
the regurgitant lesion. Medical management includes diuretics for the rare patient with pulmonary congestion. Vasodilator therapy is indicated only in the presence of concomitant
systemic hypertension and should not be advised in the
setting of normal or low systemic blood pressure.
Angiotensin-converting enzyme inhibitors are considered unsafe and are contraindicated because of their multiple adverse
effects on fetal development. There is wide experience with
hydralazine, an agent generally considered safe. When MV
surgery is required, repair is always preferred, as would be the
case for any young patient but especially in relation to the
desirability of avoiding the potential need for anticoagulation.
5.5.3. Aortic Stenosis
The most common cause of AS in pregnant women is
congenital aortic valve disease. Patients with mild obstruction
and normal LV systolic function can be managed conservatively throughout the pregnancy. Patients with moderate to
severe obstruction (Table 4)27 or symptoms should be advised
to delay conception until relief of AS can be obtained.
Women with severe AS who become pregnant but who
remain asymptomatic or have mild symptoms may often be
managed conservatively during pregnancy with bed rest,
oxygen, and beta blockers. In women with severe AS who
develop symptoms, consideration may have to be given to
either percutaneous aortic balloon valvotomy786,787 or surgery
(depending on the anatomic findings) before labor and delivery. These procedures are fraught with danger to both the
mother and fetus, although successful outcomes have been
reported. Neither is to be undertaken without caution and
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Circulation
Table 33.
October 7, 2008
Cardiovascular Drugs in Pregnancy
Drug
Use in Pregnancy
Potential Side Effects
Breast Feeding
Risk Factors
Adenosine
Maternal and fetal arrhythmias
No side effects reported; data on use during first
trimester are limited
Data NA
C
Amiodarone
Maternal arrhythmias
IUGR, prematurity, congenital goiter, hypothyroidism
and hyperthyroidism, transient bradycardia, and
prolonged QT in the newborn
Not recommended
C
Angiotensin-converting
enzyme inhibitors
Hypertension
Oligohydramnios, IUGR, prematurity, neonatal
hypotension, renal failure, anemia, death, skull
ossification defect, limb contractures, patent
ductus arteriosus
Compatible
C
Beta blockers
Hypertension, maternal arrhythmias,
myocardial ischemia, mitral
stenosis, hypertrophic
cardiomyopathy, hyperthyroidism,
Marfan syndrome
Fetal bradycardia, low placental weight, possible
IUGR, hypoglycemia, no information on carvedilol
Compatible, monitoring
of infant’s heart rate
recommended
Digoxin
Maternal and fetal arrhythmias,
heart failure
No evidence for unfavorable effects on the fetus
Compatible
C
Diltiazem
Myocardial ischemia, tocolysis
Limited data; increased incidence of major birth
defects
Compatible
C
Disopyramide
Maternal arrhythmias
Limited data; may induce uterine contraction and
premature delivery
Compatible
C
Diuretics
Hypertension, congestive heart
failure
Hypovolemia leads to reduced uteroplacental
perfusion, fetal hypoglycemia, thrombocytopenia,
hyponatremia, hypokalemia; thiazide diuretics can
inhibit labor and suppress lactation
Compatible
C
Flecainide
Maternal and fetal arrhythmias
Limited data; 2 cases of fetal death after successful
treatment of fetal SVT reported, but relation to
flecainide uncertain
Compatible
C
Heparin
Anticoagulation
None reported
Compatible
C
Hydralazine
Hypertension
None reported
Compatible
C
Lidocaine
Local anesthesia, maternal
arrhythmias
No evidence for unfavorable fetal effects; high
serum levels may cause central nervous
depression at birth
Compatible
C
Nifedipine
Hypertension, tocolysis
Fetal distress related to maternal hypotension
reported
Compatible
C
Nitrates
Myocardial infarction and ischemia,
hypertension, pulmonary edema,
tocolysis
Limited data; use is generally safe, few cases of
fetal heart rate deceleration and bradycardia have
been reported
Data NA
C
Acebutolol: B
Labetalol: C
Metoprolol: C
Propranolol: C
Atenolol: D
Procainamide
Maternal and fetal arrhythmias
Limited data; no fetal side effects reported
Compatible
C
Propafenone
Fetal arrhythmias
Limited data; fetal death reported after direct
intrauterine administration in fetuses with fetal
hydrops
Data NA
C
Quinidine
Maternal and fetal arrhythmias
Minimal oxytoxic effect, high doses may cause
premature labor or abortion; transient neonatal
thrombocytopenia and damage to eighth nerve
reported
Compatible
C
Sodium nitroprusside
Hypertension, aortic dissection
Limited data; potential thiocyanate fetal toxicity,
fetal mortality reported in animals
Data NA
C
Sotalol
Maternal arrhythmias, hypertension,
fetal tachycardia
Limited data; 2 cases of fetal death and 2 cases of
significant neurological morbidity in newborns
reported, as well as bradycardia in newborns
Compatible, monitoring
of infant’s heart rate
recommended
B
Verapamil
Maternal and fetal arrhythmias,
hypertension, tocolysis
Limited data; other than a single case of fetal death
of uncertain cause, no adverse fetal or newborn
effects have been reported
Compatible
C
Warfarin
Anticoagulation
Crosses placental barrier; fetal hemorrhage in utero,
embryopathy, central nervous system
abnormalities
Compatible
X
FDA classification: Category B: Either animal reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or
animal reproduction studies have shown an adverse effect that was not confirmed in controlled studies in women. Category C: Either studies in animals have revealed
adverse effects on the fetus and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if potential
benefits justify the potential risk to the fetus. Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant woman may be
acceptable despite the risk. Category X: Studies in animals or human beings have demonstrated fetal abnormalities. The risk of the use of the drug in pregnant women
clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. Source: Drug Information for the Health Care
Professional (USDPI Vol 1); Micromedex; 23rd ed (January 1, 2003). Adapted and modified with permission from Elkayam U. Pregnancy and cardiovascular disease.
In: Zipes DP, Libby P, Bonow RO, Braunwald E, editors. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 7th ed. Philadelphia, PA: Elsevier,
2005:1965.763 The guidelines committee added warfarin, heparin, and hydralazine to this list.
IUGR indicates intrauterine growth retardation; NA, not available; and SVT, supraventricular tachycardia.
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Bonow et al
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
forewarning. There is an association between the presence of
a bicuspid aortic valve and aortic root dilatation, which may
predispose to spontaneous aortic dissection, usually in the
third trimester, especially if there is an associated aortic
coarctation.
5.5.4. Aortic Regurgitation
Isolated AR, like MR, can usually be managed medically
with a combination of diuretics and, if necessary, vasodilator
therapy.788 Angiotensin-converting enzyme inhibitors are
considered unsafe and are contraindicated because of their
multiple adverse effects on fetal development. Women with
symptoms or signs of LV failure should be monitored
throughout labor and delivery with strict attention to volume
status and blood pressure. As is true for MR, surgery during
pregnancy should be contemplated only for control of refractory NYHA functional class III or IV symptoms. Consideration regarding LV size or systolic function in less symptomatic patients should not apply. The recommendations for
AVR based on LV size that apply to nonpregnant patients
should not be used for pregnant patients.
5.5.5. Pulmonic Stenosis
Pulmonic valve stenosis can exist in isolation but frequently
accompanies other congenital heart lesions. In general, patients with cyanotic congenital heart disease tolerate the
stresses of pregnancy far less well than those with acyanotic
lesions. Isolated pulmonic stenosis is rarely a significant
impediment to a successful pregnancy. This lesion can be
approached with percutaneous valvotomy under echocardiographic guidance when necessary.
5.5.6. Tricuspid Valve Disease
Tricuspid valve disease may be congenital (Ebstein’s anomaly, tricuspid atresia) or acquired (endocarditis, myxomatous
replacement/proliferation, carcinoid). The approach to the
patient with tricuspid valve involvement as part of a more
complex congenital heart disease syndrome is predicated on
the features of the associated lesions. Isolated TR should not
pose a significant problem during pregnancy, although greater
care may be necessary to protect against diuretic-induced
hypoperfusion.
5.5.7. Marfan Syndrome
The Marfan syndrome is an inheritable disorder of connective
tissue that often stems from abnormalities in the fibrillin gene
on chromosome 15. It is transmitted in an autosomal dominant fashion and is recognized clinically by its ocular,
skeletal, and cardiovascular expressions. Spontaneous aortic
dissection or rupture is the most feared cardiovascular complications associated with pregnancy.765,789,790 Dissection can
occur at any point along the aorta but most commonly
originates in the ascending portion. Enlargement of the aortic
root to greater than 4.0 cm identifies a particularly high-risk
group, although a normal dimension is by no means a
guarantee against this catastrophic complication. Aortic root
enlargement may or may not be accompanied by regurgitation and an audible heart murmur. MVP with regurgitation is
also frequently detected.
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Any woman with Marfan syndrome should be counseled
against pregnancy, because aortic rupture or dissection can
occur in any root size. All patients with Marfan syndrome
should have a screening transthoracic echocardiogram with
careful assessment of aortic root dimensions. Enlargement
greater than 4.5 cm is generally considered an indication for
elective repair before conception, usually with a composite
valve-graft conduit and reimplantation of the coronary arteries. If any degree of aortic root enlargement (greater than 4.0
cm) is first detected during pregnancy, some authorities
recommend termination of the pregnancy with prompt aortic
repair, although this is controversial. Less controversial is
prompt repair if serial imaging studies demonstrate progressive dilatation over time. Dissection and rupture are most
likely to occur during the third trimester or near the time of
delivery. Special care must be taken to provide adequate
analgesia to prevent wide surges in blood pressure and its rate
of rise (dP/dt) during labor and delivery. Obstetric techniques
to shorten the second stage of labor are appropriate. General
anesthesia and caesarean section may allow more optimal
hemodynamic control. The use of prophylactic beta blockade
throughout the pregnancy is strongly recommended. Such
treatment has been shown to slow the rate of aortic dilatation
and reduce the cumulative incidence of cardiovascular complications in nonpregnant adolescents and adults.359 Successful surgical correction does not confer a normal risk during
subsequent pregnancy, because such patients remain at increased for aortic dissection, albeit reduced compared with
patients with Marfan syndrome who have not undergone
surgical intervention.
5.6. Endocarditis Prophylaxis (UPDATED)
The Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the AHA does not recommend routine
antibiotic prophylaxis in patients with valvular heart disease
undergoing uncomplicated vaginal delivery or caesarean
section unless infection is suspected. Antibiotics are optional
for high-risk patients with prosthetic heart valves, a previous
history of endocarditis, complex congenital heart disease, or
a surgically constructed systemic-pulmonary conduit.1070,1072
5.7. Cardiac Valve Surgery
The performance of cardiac valve surgery is a difficult and
complex undertaking in the pregnant patient. Even under
ideal conditions, including the use of cardiopulmonary bypass
techniques that promote high flow rates and warm perfusion
temperatures, there is a high incidence of fetal distress,
growth retardation, or wastage.791–795 If possible, it is always
preferable to delay surgery until the time the fetus is viable
and a caesarean section can be performed as part of a
concomitant procedure.796,797 Surgery should be pursued only
in the setting of medically refractory cardiac symptoms
(pulmonary congestion), especially if a low-output syndrome
intervenes.
For suitable valve lesions, repair is always preferred over
replacement. If valve replacement is necessary, the choice of
a heart valve substitute can be problematic. Bioprosthetic
valves degenerate more quickly in younger patients, a process
that can be further accelerated during pregnancy.798 Although
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such valves may not require longer-term anticoagulation, they
do expose the young patient to an earlier risk of failure and need
for reoperation. Mechanical valve substitutes are more durable,
but the obligate need for anticoagulation may complicate current
and future pregnancies. For aortic valve disease, homograft
valves or pulmonary autografts should be considered.799
5.8. Anticoagulation During Pregnancy
Given the paucity of data regarding the efficacy of anticoagulants during pregnancy, recommendations concerning their
use during pregnancy are based largely on extrapolations from
data from nonpregnant patients, from case reports, and from case
series of pregnant patients.771,799 – 802
5.8.1. Warfarin
Warfarin (vitamin K antagonist therapy) crosses the placenta
and has been associated with an increased incidence of
spontaneous abortion, prematurity, and stillbirth. Warfarin
can also cause bleeding in the fetus, and fetal cerebral
hemorrhage can complicate labor and delivery, especially if
forceps evacuation is necessary. The manufacturer considers
the use of warfarin during pregnancy to be strictly contraindicated because of its association with embryopathy, consisting of nasal hypoplasia and/or stippled epiphyses after in
utero exposure during the first trimester of pregnancy, and
central nervous system abnormalities after exposure during
any trimester. The true incidence of warfarin embryopathy
has been difficult to ascertain. This has ranged from less than
5% to as high as 67%,801– 804 and an estimate of 4% to 10%
seems reasonable.805,806 However, the risk of clinically important
embryopathy may be lower if the dose of warfarin is less than or
equal to 5 mg per day.
Warfarin is probably safe during the first 6 weeks of gestation,
but there is a risk of embryopathy if warfarin is taken between 6
and 12 weeks of gestation. For women requiring long-term
warfarin therapy who are attempting pregnancy, it seems wise to
perform frequent pregnancy tests with the substitution of unfractionated heparin (UFH) or low-molecular-weight heparin
(LMWH) for warfarin when pregnancy is achieved. Warfarin is
also relatively safe during the second and third trimesters of
pregnancy but must be discontinued and switched to a heparin
compound several weeks before delivery.
5.8.2. Unfractionated Heparin
Several studies suggest that UFH or LMWH therapy is safe
for the fetus.800 – 804 Heparin does not cross the placenta and
does not have the potential to cause fetal bleeding or
teratogenicity. Thus, heparin is generally considered safer
than warfarin during pregnancy in terms of the development
of embryopathy.805,807 However, bleeding at the uteroplacental junction is possible, and numerous case series and patient
registries attest to a high incidence of thromboembolic
complications (12% to 24%), including fatal valve thrombosis, in high-risk pregnant women managed with subcutaneous
UFH or LMWH.805,808 – 810 When heparin is used during the
first trimester, the risks of maternal thromboembolism and
maternal death are more than doubled. These studies have
been criticized because of the inclusion of a predominant
population of women with older-generation and more throm-
bogenic prostheses, inadequate heparin dosing, and/or the
lack of meticulous monitoring strategies. Unfortunately, the
efficacy of adjusted-dose subcutaneous heparin has not been
definitively established.
During pregnancy, the activated partial thromboplastin
time (aPTT) response to heparin is often attenuated because
of increased levels of factor VIII and fibrinogen. Adjusteddose subcutaneous UFH can cause a persistent anticoagulant
effect at the time of delivery, which can complicate its use
before labor. Bleeding complications appear to be very
uncommon with LMWH.811
5.8.3. Low-Molecular-Weight Heparins
LMWHs have potential advantages over UFH during pregnancy because they 1) cause less heparin-induced thrombocytopenia; 2) have a longer plasma half-life and a more
predictable dose response than UFH; 3) have greater ease of
administration, with lack of need for laboratory monitoring
and the potential for once-daily dosing administration; 4) are
likely associated with a lower risk of heparin-induced osteoporosis; and 5) appear to have a low risk of bleeding
complications. They do not cross the placenta and are likely
safe for the fetus.811 Allergic skin reactions to both LMWH
and UFH can occur.
As the pregnancy progresses (and most women gain weight),
the potential volume of distribution for LMWH changes. It is
thus necessary to measure plasma anti-Xa levels 4 to 6 h after the
morning dose and adjust the dose of LMWH to achieve an
anti-Xa level of approximately 0.7 to 1.2 units per ml.
Although LMWHs have been used successfully to treat
deep venous thrombosis in pregnant patients, there are no
data to guide their use in the management of patients with
mechanical heart valves.810 Reports of LMWH use in pregnant women with prosthetic heart valves are becoming more
frequent, and many physicians now prescribe these agents
during pregnancy in women with mechanical valves, but
treatment failures have been reported. The use of LMWH
during pregnancy remains controversial because of an early
warning by the manufacturer and FDA in July 2001 regarding
safety concerns in this situation. In 2004, labeling approved
by the FDA indicated specifically that use of LMWH for
thromboprophylaxis in pregnant women with mechanical
prosthetic heart valves has not been studied adequately.
In a clinical study of pregnant women with prosthetic heart
valves given subcutaneous enoxaparin (1 mg per kg twice daily),
2 of 8 women developed prosthetic valve thromboses that led to
maternal and fetal death. Although a causal relationship has not
been established, these deaths may have been due to therapeutic
failure or inadequate anticoagulation.811
5.8.4. Selection of Anticoagulation Regimen in Pregnant
Patients with Mechanical Prosthetic Valves
Class I
1. All pregnant patients with mechanical prosthetic
valves must receive continuous therapeutic anticoagulation with frequent monitoring (see Section 9.2.).
(Level of Evidence: B)
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2. For women requiring long-term warfarin therapy who
are attempting pregnancy, pregnancy tests should be
monitored with discussions about subsequent anticoagulation therapy, so that anticoagulation can be continued uninterrupted when pregnancy is achieved.
(Level of Evidence: C)
3. Pregnant patients with mechanical prosthetic valves
who elect to stop warfarin between weeks 6 and 12 of
gestation should receive continuous intravenous UFH,
dose-adjusted UFH, or dose-adjusted subcutaneous
LMWH. (Level of Evidence: C)
4. For pregnant patients with mechanical prosthetic
valves, up to 36 weeks of gestation, the therapeutic
choice of continuous intravenous or dose-adjusted subcutaneous UFH, dose-adjusted LMWH, or warfarin
should be discussed fully. If continuous intravenous
UFH is used, the fetal risk is lower, but the maternal
risks of prosthetic valve thrombosis, systemic embolization, infection, osteoporosis, and heparin-induced
thrombocytopenia are relatively higher. (Level of Evidence: C)
5. In pregnant patients with mechanical prosthetic valves
who receive dose-adjusted LMWH, the LMWH should
be administered twice daily subcutaneously to maintain the anti-Xa level between 0.7 and 1.2 U per ml 4 h
after administration. (Level of Evidence: C)
6. In pregnant patients with mechanical prosthetic valves
who receive dose-adjusted UFH, the aPTT should be at
least twice control. (Level of Evidence: C)
7. In pregnant patients with mechanical prosthetic valves
who receive warfarin, the INR goal should be 3.0
(range 2.5 to 3.5). (Level of Evidence: C)
8. In pregnant patients with mechanical prosthetic
valves, warfarin should be discontinued and continuous intravenous UFH given starting 2 to 3 weeks before
planned delivery. (Level of Evidence: C)
Class IIa
1. In patients with mechanical prosthetic valves, it is
reasonable to avoid warfarin between weeks 6 and 12
of gestation owing to the high risk of fetal defects.
(Level of Evidence: C)
2. In patients with mechanical prosthetic valves, it is
reasonable to resume UFH 4 to 6 h after delivery and
begin oral warfarin in the absence of significant bleeding. (Level of Evidence: C)
3. In patients with mechanical prosthetic valves, it is
reasonable to give low-dose aspirin (75 to 100 mg per
day) in the second and third trimesters of pregnancy in
addition to anticoagulation with warfarin or heparin.
(Level of Evidence: C)
Class III
1. LMWH should not be administered to pregnant patients with mechanical prosthetic valves unless anti-Xa
levels are monitored 4 to 6 h after administration.
(Level of Evidence: C)
2. Dipyridamole should not be used instead of aspirin as
an alternative antiplatelet agent in pregnant patients
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with mechanical prosthetic valves because of its harmful effects on the fetus. (Level of Evidence: B)
In April 2004, labeling approved by the FDA stated that
pregnancy alone conferred an increased risk for thromboembolism and an even higher risk with thrombotic disease and
certain high-risk pregnancy conditions. Although not adequately studied, women with mechanical prosthetic heart
valves may be at higher risk for thromboembolism during
pregnancy regardless of the anticoagulant used, and when
pregnant, they have a higher rate of fetal loss from stillbirth,
spontaneous abortion, and premature delivery.
With both warfarin and UFH, monitoring is required to
assess whether the antithrombotic effects of these drugs
change during pregnancy because of alterations in intravascular volume. Both European and North American guidelines
emphasize that the use of oral coumarin derivatives throughout pregnancy targeted to an INR of 2.0 to 3.0 confers the
greatest maternal protection (5.7% risk of death or thromboembolism) and that heparin used during the first trimester
confers a lesser degree of protection. Unfortunately, these
drugs are also associated with a great risk of fetal loss (up to
30%).812
To examine the validity of these conclusions and explore
optimum antithrombotic regimens, Chan and colleagues813
performed a systematic review of the literature examining
fetal and maternal outcomes of pregnant women with prosthetic heart valves. Because no randomized trials were identified, the overview consisted of prospective and retrospective
cohort studies. This analysis suggests that warfarin is more
efficacious than UFH for thromboembolic prophylaxis of
women with mechanical heart valves in pregnancy, but with
an increased risk of embryopathy.813 The use of low-dose
UFH is inadequate; the use of adjusted-dose UFH warrants
aggressive monitoring and appropriate dose adjustment. Contemporary aPTT reagents are more sensitive to the anticoagulant effect of heparin. Therefore, a minimum target aPTT
ratio of 1.5 times the control is likely to be inadequate. A
target aPTT ratio of at least twice the control should be
attained.
Thus, there are still insufficient grounds to make definitive
recommendations about optimal antithrombotic therapy in
pregnant patients with mechanical heart valves, because
properly designed studies have not been performed. Substantial concern remains about the fetal safety of warfarin, the
efficacy of subcutaneous UFH and of LMWH in preventing
thromboembolic complications, and the risks of maternal
bleeding with various regimens. European experts have
recommended warfarin therapy throughout pregnancy in
view of the reports of poor maternal outcomes with heparin
and their impression that the risk of embryopathy with
coumarin derivatives has been overstated, especially if the
dosage of warfarin is less than or equal to 5 mg per day.
The American College of Chest Physicians Conference on
Antithrombotic and Thrombolytic Therapy814,815 concluded
that it is reasonable to use 1 of the following 3 regimens: 1)
either LMWH or UFH between 6 and 12 weeks and close to
term only, with warfarin used at other times; 2) aggressive
dose-adjusted UFH throughout pregnancy; or 3) aggressive
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adjusted-dose LMWH throughout pregnancy. Before any of
these approaches is used, it is crucial to explain the risks in
detail to the patient. If warfarin is used, the dose should be
adjusted to attain a target INR of 3.0 (range 2.5 to 3.5). If
subcutaneous UFH is used, it should be initiated in high doses
(17 500 to 20 000 U every 12 h) and adjusted to prolong a 6-h
postinjection aPTT of at least twice the control. Adjusteddose LMWH appears to be a reasonable substitute for UFH,
but further information is required about dosing during
pregnancy. If LMWH is used during pregnancy, it has been
recommended that it be administered twice daily and dosed to
achieve anti-Xa levels of 0.7 to 1.2 U per ml 4 to 6 h after
injection.771,814 The addition of aspirin 75 to 100 mg can be
considered in an attempt to reduce the risk of thrombosis, with
the recognition that it can increase the risk of bleeding.808
Dipyridamole should not be considered as an alternative
antiplatelet agent because of its harmful effects on the fetus.
Neither warfarin nor heparin is contraindicated in postpartum
mothers who breast-feed.807
5.9. Selection of Valve Prostheses in
Young Women
A major area of ongoing controversy concerns the use of
prosthetic heart valves in women likely to become pregnant.769,771 Bioprostheses are not as durable as mechanical
prostheses, although they may eliminate the need for anticoagulation therapy associated with mechanical prostheses.
Also, MV repair is preferable to MV replacement whenever
possible in women contemplating pregnancy, because it does
not require anticoagulation. Furthermore, MV balloon commissurotomy is an alternative to surgery in many patients
with MS. The Ross procedure in patients requiring AVR is an
attractive option for women who wish to become pregnant,
but this should be performed only in institutions with established expertise in this procedure.799
6. Management of Congenital Valvular Heart
Disease in Adolescents and Young Adults
(UPDATED)
Although the majority of valvular heart disease in older adults
is acquired, the predominant cause is congenital in adolescents and young adults. It has been estimated that the
prevalence of moderate or complex congenital heart disease
in adults is approximately 419 000 in the United States.816
Many patients with congenital heart disease have some
valvular involvement; frequently, it is part of a more complex
congenital cardiac anomaly, that is, tricuspid stenosis in
children with pulmonary atresia and an intact ventricular
septum or AS as part of a series of left-sided heart obstruction
lesions (Shone’s syndrome). The management of these complex diseases with multiple valve involvement is beyond the
scope of these guidelines. Rather, this section concerns
isolated valve involvement when it is the primary anatomic
abnormality.
In evaluating valvular stenosis in children, the severity of
valvular obstruction is usually reported as the peak ventricular–to–peak great artery systolic gradient at cardiac catheterization or maximum instantaneous or mean gradient by
Doppler echocardiography rather than valve area. In the
catheterization laboratory, the variation in body size from the
neonate to the adult, difficulties in measuring cardiac output
(especially in young children), and the relatively rare patient
with low cardiac output have made peak ventricular–to–peak
great artery pressure gradients for semilunar valves and atrial
a-wave–to–RV or LV end-diastolic or mean pressure gradients for atrioventricular valves the reference standards rather
than valve area. With the development of Doppler echocardiographic assessment of valvular obstruction, many pediatric
cardiologists have continued to rely on gradients calculated
from peak velocity for the semilunar valves rather than on
mean gradient or valve area. The peak gradient measured by
Doppler velocity (based on maximum instantaneous velocity)
is almost always higher than the peak ventricular–to–peak
great vessel gradient measured at catheterization. The difference between Doppler peak instantaneous and catheterization
peak-to-peak gradients is greater with AS than with pulmonic
stenosis and has resulted in most cardiologists using mean
gradients, especially in patients with AS. Significant valvular
regurgitation may exacerbate the differences. In contrast to
children and adolescents, valve area is used by many centers
in evaluation of the young adult.
Ventricular end-systolic or end-diastolic diameter or volumes
used in evaluating patients with valvular regurgitation are
frequently corrected for the large variations in body size among
adolescents and young adults. Chamber size is corrected for
body surface area (m2) or commonly by the number of standard
deviations (z score) above or below the mean with standard
nomograms that correct for body size.817
The management of the neonate, infant, and young child
differs significantly from that of the adolescent and young
adult. This section will deal exclusively with adolescents and
young adults.
6.1. Aortic Stenosis
6.1.1. Pathophysiology
Although most adults with valvular AS have a degenerativecalcific process that produces immobilization of the valve
cusps, adolescents and young adults with isolated AS almost
always have congenital fusion of 1 or more commissures that
results in a bicuspid or unicuspid valve. Although the prevalence of bicuspid and unicuspid valves may be as high as 1%
to 2%, only 1 of 50 children born with these abnormalities
will actually have significant obstruction or regurgitation by
adolescence.
For purposes of these guidelines, adolescents and young
adults are defined as patients with minimally calcified valves
who are less than 30 years old. Some adults with minimally
calcified valves who are more than 30 years old may also
benefit under these guidelines.
Much of what has been written in these guidelines for
adults with acquired AS may be transferred to the adolescent
or young adult (see Section 3.1.); however, certain important
differences must be emphasized. Throughout childhood, the
aortic annulus and aortic valve must grow in parallel with
somatic growth. If growth of either the annulus or valve
leaflets lags, increased obstruction may occur. Therefore, the
rate of progression during childhood and adolescent growth
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can be different from that in the adult with acquired heart
disease. The report from the joint study on the Natural
History of Congenital Heart Defects818 followed 473 patients
(before the advent of echocardiography), 60% of whom were
initially evaluated between 2 and 11 years of age and 34%
between 11 and 21 years of age. One third of the children had
an increase in the transaortic gradient measured by cardiac
catheterization during the 4- to 8-year follow-up period.
However, the 54 patients greater than 12 years of age showed
very small increases. Those with higher initial gradients had
a greater likelihood of demonstrating an increase in the
gradient.
Long-term results of the original cohort have been reported,819
with a mean follow-up period of 20 years. Only 20% of those
with initial peak LV–to–peak aortic pressure gradients less
than 25 mm Hg at initial catheterization had any intervention.
However, in those with an initial catheter-derived LV–to–
peak aortic gradient greater than 50 mm Hg, arrhythmias,
sudden death, or other morbid events (including endocarditis,
congestive heart failure, syncope, angina, myocardial infarction, stroke, and pacemaker insertion) occurred at a rate on
average of 1.2% per year. Sudden cardiac death occurred in
25 of the 370 patients followed up over an average of 8000
patient years, for an average incidence of 0.3% per year. The
severity of obstruction in those who died could not be determined, and a higher-risk subgroup could not be excluded.
6.1.2. Evaluation of Asymptomatic Adolescents or Young
Adults With Aortic Stenosis
Class I
1. An ECG is recommended yearly in the asymptomatic
adolescent or young adult with AS who has a Doppler
mean gradient greater than 30 mm Hg or a peak
velocity greater than 3.5 m per second (peak gradient
greater than 50 mm Hg) and every 2 years if the
echocardiographic Doppler mean gradient is less than
or equal to 30 mm Hg or the peak velocity is less than
or equal to 3.5 m per second (peak gradient less than or
equal to 50 mm Hg). (Level of Evidence: C)
2. Doppler echocardiography is recommended yearly in
the asymptomatic adolescent or young adult with AS
who has a Doppler mean gradient greater than 30 mm
Hg or a peak velocity greater than 3.5 m per second
(peak gradient greater than 50 mm Hg) and every 2
years if the Doppler gradient is less than or equal to 30
mm Hg or the peak jet velocity is less than or equal to
3.5 m per second (peak gradient less than or equal to 50
mm Hg). (Level of Evidence: C)
3. Cardiac catheterization for the evaluation of AS is an
effective diagnostic tool in the asymptomatic adolescent
or young adult when results of Doppler echocardiography are equivocal regarding severity of AS or when there
is a discrepancy between clinical and noninvasive findings
regarding severity of AS. (Level of Evidence: C)
4. Cardiac catheterization is indicated in the adolescent
or young adult with AS who has symptoms of angina,
syncope, or dyspnea on exertion if the Doppler mean
gradient is greater than 30 mm Hg or the peak velocity
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is greater than 3.5 m per second (peak gradient greater
than 50 mm Hg). (Level of Evidence: C)
5. Cardiac catheterization is indicated in the asymptomatic adolescent or young adult with AS who develops
T-wave inversion at rest over the left precordium if the
Doppler mean gradient is greater than 30 mm Hg or
the peak velocity is greater than 3.5 m per second
(peak gradient greater than 50 mm Hg). (Level of
Evidence: C)
Class IIa
1. Graded exercise testing is a reasonable diagnostic
evaluation in the adolescent or young adult with AS
who has a Doppler mean gradient greater than 30 mm
Hg or a peak velocity greater than 3.5 m per second
(peak gradient greater than 50 mm Hg) if the patient is
interested in athletic participation, or if the clinical
findings and Doppler findings are disparate. (Level of
Evidence: C)
2. Cardiac catheterization for the evaluation of AS is a
reasonable diagnostic tool in the asymptomatic adolescent or young adult who has a Doppler mean gradient
greater than 40 mm Hg or a peak velocity greater than
4 m per second (peak gradient greater than 64 mm
Hg). (Level of Evidence: C)
3. Cardiac catheterization for the evaluation of AS is
reasonable in the adolescent or young adult who has a
Doppler mean gradient greater than 30 mm Hg or a
peak velocity greater than 3.5 m per second (peak
gradient greater than 50 mm Hg) if the patient is
interested in athletic participation or becoming
pregnant, or if the clinical findings and the Doppler
echocardiographic findings are disparate. (Level of
Evidence: C)
The diagnosis of AS can usually be made clinically, with
severity estimated by ECG and Doppler echocardiographic
studies. Diagnostic cardiac catheterization is occasionally
required if there is a discrepancy among clinical evaluation,
ECG, and/or Doppler echocardiographic findings. Exercise
testing may be useful, especially in those interested in athletic
participation. Diagnostic cardiac catheterization may be helpful if the clinical findings and the Doppler echocardiographic
assessment are disparate.
6.1.3. Indications for Aortic Balloon Valvotomy in
Adolescents and Young Adults
Class I
1. Aortic balloon valvotomy is indicated in the adolescent
or young adult patient with AS who has symptoms of
angina, syncope, or dyspnea on exertion and a catheterization peak LV–to–peak aortic gradient greater
than or equal to 50 mm Hg without a heavily calcified
valve. (Level of Evidence: C)*
2. Aortic balloon valvotomy is indicated for the asymptomatic adolescent or young adult patient with AS who
*Gradients are usually obtained with patients sedated. If general anesthesia is used, the gradients may be somewhat lower.
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has a catheterization peak LV–to–peak aortic gradient
greater than 60 mm Hg. (Level of Evidence: C)*
3. Aortic balloon valvotomy is indicated in the asymptomatic adolescent or young adult patient with AS who
develops ST or T-wave changes over the left precordium on ECG at rest or with exercise and who has a
catheterization peak LV–to–aortic gradient greater
than 50 mm Hg. (Level of Evidence: C)*
Class IIa
1. Aortic balloon valvotomy is reasonable in the asymptomatic adolescent or young adult patient with AS
when catheterization peak LV–to–peak aortic gradient
is greater than 50 mm Hg and the patient wants to play
competitive sports or desires to become pregnant.
(Level of Evidence: C)*
2. In the adolescent or young adult patient with AS,
aortic balloon valvotomy is probably recommended
over valve surgery when balloon valvotomy is possible.
Patients should be referred to a center with expertise in
balloon valvotomy. (Level of Evidence: C)*
Class III
1. Aortic balloon valvotomy should not be performed
when the asymptomatic adolescent or young adult
patient with AS has a catheterization peak LV–to–peak
aortic gradient less than 40 mm Hg without symptoms
or ECG changes. (Level of Evidence: C)*
Balloon valvotomy for calcific AS in older adults constitutes
at best very short-term palliation. In contrast, balloon valvotomy in children and adolescents with obstruction due to
fusion of commissures is considerably more efficacious.
There are insufficient published data to establish an age
cutoff. Until more information becomes available, recommendations for balloon valvotomy should be limited to adolescents and young adults. In a large collaborative registry
involving 606 patients from 23 institutions, the peak LV–to–
peak aortic pressure gradients at catheterization were reduced
by a mean of 60%.820 In a single-institution study of 148
patients dilated at age 1 month to 20 years,821 midterm results
showed an 8-year actuarial survival of 95%, with 3 of the 4
deaths occurring in infants who were dilated at less than 1
year of age. Seventy percent of patients were free from operation
and 50% were free from intervention 8 years after dilation,
which was similar to results reported with surgical valvuloplasty.
Long-term follow-up information is incomplete because balloon
valvotomy was not introduced until the 1980s.
Although balloon dilation has become standard in children
and adolescents with AS, it is rarely recommended in older
adults with calcific valves, because even short-term palliation
is uncommon. Because balloon valvotomy has resulted in
good midterm palliation with little morbidity and little or no
short- or intermediate-term mortality in children, adolescents,
and young adults, the indications for intervention are considerably more liberal than those in older adults, in whom
intervention usually involves valve replacement.
Surgical valvotomy is of historic interest but is now rarely
used except in situations in which interventional cardiologists
are not available. Children and young adults with peak
Doppler gradients of 64 mm Hg or more or mean gradients
greater than 40 mm Hg and those with symptoms may be
considered for cardiac catheterization and possible balloon
dilation. Patients with lower gradients (50 mm Hg peak or 30
mm Hg mean) are sometimes referred for catheterization if
they are interested in participating in athletics, are contemplating pregnancy, or have developed ST–T-wave changes
over the left precordium at rest or with exercise. The gradient
should be confirmed hemodynamically before proceeding
with dilation. Gradients are usually obtained with the patient
sedated. If general anesthesia is used, the gradients may be
lower. It is reasonable to perform valvotomy in asymptomatic
patients with catheterization gradients greater than 60 mm Hg
and in some patients with a catheterization peak LV–to–peak
aortic pressure gradient of 50 to 60 mm Hg who have
symptoms, have associated ischemic changes on rest or
exercise ECG, are interested in participating in vigorous
athletics, or are contemplating pregnancy. In those children
who have had a balloon valvuloplasty when younger, a repeat
attempt is usually tried before surgical valve replacement
using the above criteria if significant AR is not present.
When balloon aortic valvotomy is ineffective or significant
AR is present, valve repair or replacement may be necessary.
Long-term follow-up into adulthood is mandatory, because
the long-term cumulative risks of endocarditis, thromboembolism, and bleeding from anticoagulation over 20- to 40year follow-up have been problematic, and progressive stenosis has been observed.153,822 Because degeneration of
homograft or bioprosthetic valves is usually accelerated in the
young (see Sections 7.2 and 7.3), AVR is usually performed
with a mechanical valve. Recently, there has been a renewed
interest in valve repair or the Ross operation,153,822 that is,
moving the native pulmonary valve to the aortic position
using a homograft to replace the pulmonary valve. Three
studies from the Netherlands (343 patients; mean age 26
years),823 Canada (155 patients; mean age 35 years),824 and
the United States (328 patients)825 have shown relatively low
operative mortality (2.6%, 0.6%, and 4.6%, respectively) with
actuarial survival of 94% and 98% at 7 years in 2 of the studies
and 89.9% at 8 years in the other. The most common complications were AR, usually secondary to neoaortic root dilation,
and RV outflow tract obstruction, with intervention necessary in
approximately 10% of patients within 7 to 10 years.
Although the Ross operation, homograft, heterograft, and
valve repair each appear to offer an attractive alternative to a
mechanical valve for those with a relative contraindication to
warfarin for anticoagulation (e.g., athletes or woman desiring
pregnancy), in the absence of long-term results, it is not
believed that the indications for surgery with the Ross
operation, heterograft, or homograft differ from those for
mechanical valve replacement at this time.
6.2. Aortic Regurgitation
Class I
1. An adolescent or young adult with chronic severe AR*
with onset of symptoms of angina, syncope, or dyspnea
*See Table 4.27
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on exertion should receive aortic valve repair or replacement. (Level of Evidence: C)
2. Asymptomatic adolescent or young adult patients with
chronic severe AR* with LV systolic dysfunction (ejection fraction less than 0.50) on serial studies 1 to 3
months apart should receive aortic valve repair or
replacement. (Level of Evidence: C)
3. Asymptomatic adolescent or young adult patients with
chronic severe AR* with progressive LV enlargement
(end-diastolic dimension greater than 4 standard deviations above normal) should receive aortic valve repair
or replacement. (Level of Evidence: C)
4. Coronary angiography is recommended before AVR in
adolescent or young adult patients with AR in whom a
pulmonary autograft (Ross operation) is contemplated
when the origin of the coronary arteries has not been
identified by noninvasive techniques. (Level of Evidence: C)
Class IIb
1. An asymptomatic adolescent with chronic severe AR*
with moderate AS (peak LV–to–peak aortic gradient
greater than 40 mm Hg at cardiac catheterization) may
be considered for aortic valve repair or replacement.
(Level of Evidence: C)
2. An asymptomatic adolescent with chronic severe AR*
with onset of ST depression or T-wave inversion over the
left precordium on ECG at rest may be considered for
aortic valve repair or replacement. (Level of Evidence: C)
AR is an uncommon isolated congenital lesion, although it
may occasionally develop in adolescents and young adults
with a bicuspid aortic valve, discrete subaortic obstruction, or
prolapse of 1 aortic cusp into a ventricular septal defect. It is
commonly the consequence of attempts to relieve stenosis of
the valve by either balloon dilation or surgical valvulotomy,
as part of a connective tissue disorder, or when the pulmonary
artery is relocated in the aortic position (Ross procedure or
arterial switch repair of transposition). The indications for
surgery with severe isolated AR or mixed aortic valve disease
are at present similar to those for adults, that is, symptoms,
LV dysfunction (ejection fraction less than 0.50), or very
increased LV end-diastolic or end-systolic diameter, taking
into account variations in body size. If the durability of
pulmonary autograft and homograft valves in the RV outflow
tract is substantiated in long-term studies, the indications for
autograft valve replacement are likely to become more
liberal. Surgery has usually involved mechanical or biological
valve replacement (see Sections 3.2.3.8 and 7.2), but some
have performed the Ross operation or aortic valve repair.
Although not all valves are amenable to repair, some success
has been reported for AR after balloon dilation (100%
freedom from reoperation at 1 year and 80% from reintervention at 3 years)826 and with a prolapsing leaflet (freedom
from reoperation of 95%, 87%, and 84% at 1, 5, and 7 years,
respectively).827 Aortic valve repair is a viable alternative in
some centers and may be preferred in the future, but in view
of the relative youth of the patients and lack of long-term
durability of valve repair or replacement with biological
valves, these alternatives to mechanical valve replacement
may be appropriate only for those with a contraindication to
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anticoagulation in the majority of centers. Indications for
surgery in patients with AR and dilated aortic roots or
ascending aortas are the same as in older adult patients (see
Sections 3.2.4 and 3.3).
6.3. Mitral Regurgitation
Class I
1. MV surgery is indicated in the symptomatic adolescent or
young adult with severe congenital MR* with NYHA
functional class III or IV symptoms. (Level of Evidence: C)
2. MV surgery is indicated in the asymptomatic adolescent or young adult with severe congenital MR* and
LV systolic dysfunction (ejection fraction less than or
equal to 0.60). (Level of Evidence: C)
Class IIa
1. MV repair is reasonable in experienced surgical centers
in the asymptomatic adolescent or young adult with
severe congenital MR* with preserved LV systolic function if the likelihood of successful repair without residual
MR is greater than 90%. (Level of Evidence: B)
Class IIb
1. The effectiveness of MV surgery is not well established
in asymptomatic adolescent or young adult patients
with severe congenital MR* and preserved LV systolic
function in whom valve replacement is highly likely.
(Level of Evidence: C)
MR caused by myxomatous MV disease and MVP is a
common congenital lesion, but other forms of isolated congenital MR are extremely uncommon. MR can be associated
with MVP in adolescents or young adults with connective
tissue, metabolic, or storage diseases. It can be seen with
acquired inflammatory diseases such as rheumatic fever,
endocarditis, or Kawasaki disease or with certain collagen
vascular disorders.
MR also develops commonly in children with primum
atrioventricular septal defects. These defects are caused by a
deficiency of the atrioventricular septum in the embryonic
heart. There may be an isolated ostium primum atrial septal
defect; ventricular septal defect in the inlet (posterior) septum; abnormalities of the mitral or tricuspid valve, including
clefts; or some combination of the above. In a complete
atrioventricular septal defect, there is a combination of a large
primum atrial septal defect, a large inlet (posterior) ventricular septal defect, and a common atrioventricular valve that
failed to develop into separate mitral and tricuspid valves.
Repair of the defects in early childhood, with low mortality
and morbidity, is now commonplace. The most common
long-term sequela of surgery is MR, which can be mild,
moderate, or severe.
The pathophysiology, diagnosis, and medical therapy of
residual MR in atrioventricular septal defects, rheumatic
fever, or MVP are similar to those discussed for the adult with
MR (Section 3.5). When MR is associated with symptoms or
*See Table 4.27
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deteriorating LV systolic function on echocardiography or
angiography, surgery should be performed. In children with
MR associated with atrioventricular septal defects, the MR
can usually be reduced or eliminated with surgery. In patients
with MR after atrioventricular septal defect repair or MR
secondary to MVP, rheumatic fever, or inflammatory disease,
it is usually possible to decrease the MR with MV repair and
annular reduction. Rarely, MV replacement with a mechanical or biological valve is necessary. When valve repair rather
than replacement is likely, surgery for severe MR is frequently performed in asymptomatic patients before the development of heart failure or LV dysfunction. On the other
extreme, for symptomatic patients with MR and severe LV
dysfunction, cardiac transplantation may be the preferred
option to MV replacement or repair.
6.4. Mitral Stenosis
Class I
1. MV surgery is indicated in adolescent or young adult
patients with congenital MS who have symptoms
(NYHA functional class III or IV) and mean MV
gradient greater than 10 mm Hg on Doppler echocardiography.* (Level of Evidence: C)
Class IIa
1. MV surgery is reasonable in adolescent or young adult
patients with congenital MS who have mild symptoms
(NYHA functional class II) and mean MV gradient
greater than 10 mm Hg on Doppler echocardiography.* (Level of Evidence: C)
2. MV surgery is reasonable in the asymptomatic adolescent or young adult with congenital MS with pulmonary artery systolic pressure 50 mm Hg or greater and
a mean MV gradient greater than or equal to 10 mm
Hg.* (Level of Evidence: C)
Class IIb
1. The effectiveness of MV surgery is not well established
in the asymptomatic adolescent or young adult with
congenital MS and new-onset atrial fibrillation or
multiple systemic emboli while receiving adequate
anticoagulation.* (Level of Evidence: C)
In developed countries, MS in adolescents and young adults
is often congenital in origin. In developing areas of the world,
MS is more likely to result from rheumatic fever. Congenital
MS is usually classified by the component of the mitral
apparatus that is abnormal, that is, the leaflets, annulus,
chordae, or papillary muscles. Frequently, multiple valve
components are involved, which results in rolled, thickened
leaflet margins; shortened and thickened chordae tendineae;
obliteration of the interchordal spaces with abnormal chordal
insertions; papillary muscle hypoplasia; and fusion of the
anterolateral and posteromedial papillary muscles.828 This
latter condition causes the mitral apparatus to appear like a
funnel or a parachute. MS results from the inability of blood
*See Table 4.27
to pass unobstructed from the left atrium to the LV through a
very abnormal mitral apparatus.
Congenital MS may be associated with a wide variety of
other congenital cardiac malformations of the left side of the
heart, including bicuspid aortic valve and AS, supravalvar
mitral ring, and/or coarctation of the aorta.
The clinical, electrocardiographic, and radiologic features
of congenital MS are similar to those of acquired MS in
adults. The echocardiogram is essential in evaluating the MV
apparatus and papillary muscles and may provide considerable insight into the feasibility of successful valve repair. The
information obtained from transthoracic imaging is usually
sufficient, but in adolescents and young adults, a transesophageal echocardiogram is sometimes necessary.
Medical management including beta blockers and diuretics
may be of some utility with mild MS. It is important to
prevent and treat common complications such as pulmonary
infections, endocarditis, and atrial fibrillation. Surgical intervention may be necessary in severe cases. The surgical
management of congenital MS has improved considerably
with the improved appreciation of the mechanism of MV
function and the improved ability to visualize the valve
afforded by transesophageal echocardiography. In those patients with a parachute MV, creation of fenestrations among
the fused chordae may increase effective orifice area and
improve symptoms dramatically. MV replacement may occasionally be necessary but is especially problematic in those
with a hypoplastic mitral annulus, in whom an annulusenlarging operation may be necessary. Recently, balloon
dilation of congenital MS has been attempted,829 but its utility
is limited in patients with significant stenosis of the subvalvular apparatus. This is one of the most difficult and dangerous therapeutic catheterization procedures and should be
undertaken only in centers with operators who have established experience and skill in this interventional procedure. In
adolescent and young adult patients with rheumatic MS, the
results of balloon dilation are similar to those in older adults
(see Section 3.4.8). Pulmonary artery hypertension usually
resolves with relief of the MS.
6.5. Tricuspid Valve Disease
6.5.1. Pathophysiology
Acquired disease of the tricuspid valve is very uncommon in
adolescents and young adults. Other than occasional cases of
TR secondary to trauma, bacterial endocarditis in intravenous
drug abusers, and small ventricular septal defects in adolescents in whom the jet through the ventricular septum creates
endothelial damage to the tricuspid valve, virtually all cases
of acquired TR are limited to case reports.
Most cases of tricuspid valve disease are congenital, with
Ebstein’s anomaly of the tricuspid valve being the most
common. In Ebstein’s anomaly, there is inferior displacement
of the septal and posterior leaflets of the valve into the right
ventricle. If there is significant adherence of the leaflets to the
RV wall, the normal or relatively normal anterior leaflet fails
to coapt with the abnormal posterior leaflet, creating severe
TR. If the valve leaflets are not adherent, there is redundancy
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of valve tissue with severe prolapse associated with varying
degrees of TR.
There is wide variation in the severity of valve leaflet
abnormalities in Ebstein’s disease. Some children may have
severe TR, especially in the perinatal period, when pulmonary vascular resistance and resulting RV pressures are high.
Others have very mild abnormalities that may not be recognized until a chest X-ray obtained for other reasons shows
cardiomegaly. An interatrial communication, usually in the
form of a patent foramen ovale, is present in most cases. If TR
elevates right atrial pressure above left atrial pressure, rightto-left shunting can occur, with resulting hypoxemia. One or
more accessory conduction pathways are quite common, with
a risk of paroxysmal atrial tachycardia of approximately 25%.
Patients with Ebstein’s anomaly may be asymptomatic
with no cyanosis and no atrial arrhythmias. They often are
cyanotic owing to right-to-left shunting,830 which is associated with exercise intolerance. RV dysfunction may eventually lead to right-sided congestive heart failure frequently
exacerbated by an atrial arrhythmia such as atrial tachycardia,
atrial flutter, or atrial fibrillation. Exercise testing may be
useful in determining symptom status and degree of exerciseinduced arterial desaturation.
The natural history of Ebstein’s anomaly varies. In patients
who present in the perinatal period, the 10-year actuarial
survival is 61%.831 In a study that included more children
who presented after the perinatal period, the probability of
survival was 50% at 47 years of age.832 Predictors of poor
outcome include NYHA functional class III or IV symptoms,
cardiothoracic ratio greater than 65%, atrial fibrillation, severity of cyanosis, and magnitude of TR. However, patients
with Ebstein’s anomaly who reach late adolescence and
adulthood often have an excellent outcome.832
6.5.2. Evaluation of Tricuspid Valve Disease in Adolescents
and Young Adults
Class I
1. An ECG is indicated for the initial evaluation of adolescent and young adult patients with TR, and serially every
1 to 3 years, depending on severity. (Level of Evidence: C)
2. Chest X-ray is indicated for the initial evaluation of
adolescent and young adult patients with TR, and
serially every 1 to 3 years, depending on severity.
(Level of Evidence: C)
3. Doppler echocardiography is indicated for the initial
evaluation of adolescent and young adult patients with
TR, and serially every 1 to 3 years, depending on
severity. (Level of Evidence: C)
4. Pulse oximetry at rest and/or during exercise is indicated for the initial evaluation of adolescent and young
adult patients with TR if an atrial communication is
present, and serially every 1 to 3 years, depending on
severity. (Level of Evidence: C)
Class IIa
1. If there is a symptomatic atrial arrhythmia, an electrophysiology study can be useful for the initial evalu-
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ation of adolescent and young adult patients with TR.
(Level of Evidence: C)
2. Exercise testing is reasonable for the initial evaluation
of adolescent and young adult patients with TR, and
serially every 1 to 3 years. (Level of Evidence: C)
Class IIb
1. Holter monitoring may be considered for the initial
evaluation of asymptomatic adolescent and young
adult patients with TR, and serially every 1 to 3 years.
(Level of Evidence: C)
6.5.3. Indications for Intervention in Tricuspid
Regurgitation
Class I
1. Surgery for severe TR is recommended for adolescent
and young adult patients with deteriorating exercise
capacity (NYHA functional class III or IV). (Level of
Evidence: C)
2. Surgery for severe TR is recommended for adolescent
and young adult patients with progressive cyanosis and
arterial saturation less than 80% at rest or with
exercise. (Level of Evidence: C)
3. Interventional catheterization closure of the atrial
communication is recommended for the adolescent or
young adult with TR who is hypoxemic at rest and with
exercise intolerance due to increasing hypoxemia with
exercise, when the tricuspid valve appears difficult to
repair surgically. (Level of Evidence: C)
Class IIa
1. Surgery for severe TR is reasonable in adolescent and
young adult patients with NYHA functional class II
symptoms if the valve appears to be repairable. (Level
of Evidence: C)
2. Surgery for severe TR is reasonable in adolescent and
young adult patients with atrial fibrillation. (Level of
Evidence: C)
Class IIb
1. Surgery for severe TR may be considered in asymptomatic adolescent and young adult patients with increasing heart size and a cardiothoracic ratio of more
than 65%. (Level of Evidence: C)
2. Surgery for severe TR may be considered in asymptomatic adolescent and young adult patients with stable heart
size and an arterial saturation of less than 85% when the
tricuspid valve appears repairable. (Level of Evidence: C)
3. In adolescent and young adult patients with TR who are
mildly cyanotic at rest but who become very hypoxemic
with exercise, closure of the atrial communication by
interventional catheterization may be considered when
the valve does not appear amenable to repair. (Level of
Evidence: C)
4. If surgery for Ebstein’s anomaly is planned in adolescents and young adult patients (tricuspid valve repair
or replacement), a preoperative electrophysiological
study may be considered to identify accessory pathways. If present, these may be considered for mapping
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and ablation either preoperatively or at the time of
surgery. (Level of Evidence: C)
Surgical management of Ebstein’s anomaly remains challenging.833 A Glenn anastomosis between the superior vena
cava and right pulmonary artery is occasionally performed to
reduce the volume load on the right ventricle. For adolescents
and young adults, tricuspid valve repair has been attempted.
Reconstruction of the valve is possible, especially when there
is a mobile anterior leaflet free of tethering to the ventricular
septum. Valvuloplasty may be performed with positioning of
the displaced leaflet of the tricuspid valve to the normal level,
sometimes with placation of the atrialized portion of the right
ventricle to reduce its size. If TR is mild and hypoxemia at
rest or exercise is problematic, closure of the atrial septal
defect in the catheterization laboratory has been successful in
eliminating the hypoxemia.
Occasionally, the tricuspid valve is not reparable, and
valve replacement with a bioprosthesis or a mechanical valve
may be necessary.834 When present, atrial communications
should be closed unless significant postoperative TR or RV
dysfunction is anticipated and the presence of an atrial septal
defect may allow decompression of the right atrium. If an
accessory pathway is present, this should be mapped and
ablated either preoperatively in the electrophysiology laboratory or at the time of surgery.
and serially every 5 to 10 years for follow-up examinations. (Level of Evidence: C)
2. Transthoracic Doppler echocardiography is recommended for the initial evaluation of pulmonic stenosis
in adolescent and young adult patients, and serially
every 5 to 10 years for follow-up examinations. (Level
of Evidence: C)
3. Cardiac catheterization is recommended in the adolescent or young adult with pulmonic stenosis for evaluation of the valvular gradient if the Doppler peak jet
velocity is greater than 3 m per second (estimated peak
gradient greater than 36 mm Hg) and balloon dilation
can be performed if indicated. (Level of Evidence: C)
Class III
1. Diagnostic cardiac catheterization is not recommended
for the initial diagnostic evaluation of pulmonic stenosis in adolescent and young adult patients. (Level of
Evidence: C)
The clinical diagnosis of pulmonary valve stenosis is straightforward, and the severity can usually be determined accurately by 2D and Doppler echocardiography. Diagnostic
catheterization is rarely required.
6.6.3. Indications for Balloon Valvotomy in Pulmonic Stenosis (UPDATED)
6.6. Pulmonic Stenosis
Class I
6.6.1. Pathophysiology
Because the pulmonary valve is the least likely valve to be
affected by acquired heart disease, virtually all cases of
pulmonary valve stenosis are congenital in origin. Most
patients with stenosis have a conical or dome-shaped pulmonary valve formed by fusion of the valve leaflets. Occasionally, the valve may be thickened and dysplastic, with the
stenosis caused by inability of the valve leaflets to separate
sufficiently during ventricular systole.835
Symptoms are unusual in children or adolescents with
pulmonary valve stenosis even when severe. Adults with
long-standing severe obstruction may have dyspnea and
fatigue secondary to an inability to increase cardiac output
adequately with exercise. Exertional syncope or lightheadedness may occur in the presence of severe pulmonic
stenosis with systemic or suprasystemic RV pressures, with
decreased preload or dehydration, or with a low systemic
vascular resistance state (such as pregnancy). However,
sudden death is very unusual. Eventually, with long-standing
untreated severe obstruction, TR and RV failure may occur.
At any age, if the foramen ovale is patent, RV compliance
may be reduced sufficiently to elevate right atrial pressure,
which allows right-to-left shunting and cyanosis. This increases the risk of paradoxical emboli.
1. Balloon valvotomy is recommended in adolescent and
young adult patients with pulmonic stenosis who have
exertional dyspnea, angina, syncope, or presyncope
and an RV–to–pulmonary artery peak-to-peak gradient greater than 30 mm Hg at catheterization. (Level of
Evidence: C)
2. Balloon valvotomy is recommended in asymptomatic
adolescent and young adult patients with pulmonic stenosis and RV–to–pulmonary artery peak-to-peak gradient greater than 40 mm Hg at catheterization. (Level of
Evidence: C)
6.6.2. Evaluation of Pulmonic Stenosis in Adolescents and
Young Adults
Class I
1. An ECG is recommended for the initial evaluation of
pulmonic stenosis in adolescent and young adult patients,
Class IIb
1. Balloon valvotomy may be reasonable in asymptomatic
adolescent and young adult patients with pulmonic
stenosis and an RV–to–pulmonary artery peak-to-peak
gradient 30 to 39 mm Hg at catheterization. (Level of
Evidence: C)
Class III
1. Balloon valvotomy is not recommended in asymptomatic
adolescent and young adult patients with pulmonic stenosis and RV–to–pulmonary artery peak-to-peak gradient less than 30 mm Hg at catheterization. (Level of
Evidence: C)
The clinical course of children and young adults with pulmonary valve stenosis has been well described. The Natural
History of Congenital Heart Defects study836 in the mid 1960s
and early 1970s followed 564 patients with valvar pulmonary
stenosis with cardiac catheterization at 4- and 8-year inter-
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vals. On admission to the study, an average of 15% of patients
were less than 2 years old; 20% were 12 to 21 years old; and
the remainder were 2 to 11 years old. At initial cardiac
catheterization, they were divided into 4 groups based on
severity: less than 25 mm Hg peak-to-peak gradient between
the right ventricle and the pulmonary artery, trivial; 25 to 49
mm Hg, mild; 50 to 79 mm Hg, moderate; and greater than 80
mm Hg, severe.
Of the 261 patients (46% of the total) treated medically,
most had trivial, mild, or moderate obstruction. None of these
patients had cyanosis or congestive heart failure, and only 6%
had symptoms. There were no deaths during the study. The
pressure gradients were stable in the majority, with 14% of
patients manifesting a significant increase and 14% a significant decrease. Most of the increases were in children less
than 2 years old and/or those with initial gradients greater
than 40 mm Hg. Those not in either category had only a 4%
chance of an increase in the gradient greater than 20 mm Hg.
There was little or no change in the overall status of the
medically treated patients. During the period of observation,
304 patients, most with moderate or severe disease, were
treated surgically. Only 1 death occurred among the 245
patients in this group who underwent surgery beyond infancy.
At postoperative follow-up, the gradient had been reduced to
insignificant levels in more than 90%, with no recurrence of
pulmonary stenosis in those followed up to 14 years.
In 1993, the second Natural History of Congenital Heart
Defects study837 reported on the 16- to 29-year (mean 22
years) follow-up of the same group of patients. The probability of 25-year survival was 96%, not statistically different
from the normal control group. Fewer than 20% of patients
managed medically during the first Natural History Study
subsequently required a valvotomy, and only 4% of the
patients who had undergone surgery required a second
operation. Most patients, whether managed medically or
surgically, had mild obstruction by Doppler echocardiography. For patients who had an initial transpulmonary gradient
less than 25 mm Hg in the first Natural History Study, 96%
were free of cardiac operation over a 25-year period.
Surgical relief of severe obstruction by valvotomy with a
transventricular838 or transpulmonary artery839 approach predates the introduction of cardiopulmonary bypass. A nonsurgical approach with balloon valvotomy was described in
1982840 and by the late 1980s had become the procedure of
choice in the United States for the typically domed, thickened
valve, both for children841 and adults.842,843 Surgery is still
usually required for the dysplastic valve often seen in Noonan’s
syndrome. Although long-term follow-up of pulmonary balloon
valvotomy is not yet available, the early and midterm results (up
to 10 years)844 suggest that the long-term results will be similar
to surgical valvotomy, that is, little or no recurrence over a 22to 30-year period. Some pulmonary regurgitation almost invariably occurs after valvuloplasty, but it is rarely clinically important in this group.
In those with severe or long-standing valvular obstruction,
infundibular hypertrophy may cause secondary obstruction
when the pulmonary valve is successfully dilated. This
frequently regresses over time without treatment. Some have
advocated transient pharmacological beta blockade, but there
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is insufficient information to determine whether this is effective or necessary.
From the Natural History Study data, it appears that
congenital mild pulmonary stenosis is a benign disease that
rarely progresses, that moderate or severe pulmonary stenosis
can be improved with either surgery or balloon valvotomy at
very low risk, and that patients who undergo surgery or
balloon valvotomy have an excellent prognosis and a low rate
of recurrence. Thus, the goal of the clinician is to ascertain the
severity of the disease, treat those in whom it is moderate or
severe, and infrequently follow up on those with mild
disease.845
6.7. Pulmonary Regurgitation
Pulmonary valve regurgitation is an uncommon congenital
lesion seen occasionally with what has been described as
idiopathic dilation of the pulmonary artery or with connective
tissue disorders. In this condition, the annulus of the pulmonary valve dilates, which causes failure of the leaflets to coapt
during diastole. Mild pulmonary regurgitation may be a
normal finding on Doppler echocardiography.
Although pulmonary regurgitation is unusual as an isolated
congenital defect, it is an almost unavoidable result of either
surgical or balloon valvuloplasty of valvular pulmonic stenosis or surgical repair of tetralogy of Fallot. Among patients
with pulmonic stenosis who underwent surgical valvotomy in
the first Natural History Study,836 87% had pulmonary regurgitation by Doppler echocardiography in the second Natural
History Study,837 although it was audible in only 58%. The
echocardiogram tended to overestimate severity compared
with auscultation, with 20% considered moderate to severe by
Doppler but only 6% by auscultation. In those with pulmonary regurgitation, the right ventricle tended to be larger, but
RV systolic dysfunction was uncommon, being present in
only 9%.
Pulmonary regurgitation also commonly occurs after successful repair of tetralogy of Fallot. Several studies have
documented that the vast majority of children and young
adults who underwent surgery in the late 1950s and 1960s
continued to do well for up to 35 years after surgery.846
However, an increasing number of patients with longstanding pulmonary regurgitation have developed severe RV
dilatation and diminished RV systolic performance, which
can lead to an inadequate ability to augment cardiac output
with exercise and, in some cases, congestive heart failure.
This group has also been shown to have a significant
incidence of ventricular arrhythmias known to be associated
with late sudden death. Increased pulmonary artery pressure
from LV dysfunction or residual peripheral pulmonary artery
stenosis will increase the amount of regurgitation, and these
conditions should be treated when present. Cardiac magnetic
resonance has proven to be a useful tool for evaluating
pulmonary regurgitant fraction, RV end-diastolic and endsystolic volumes, and RV ejection fraction. A wide variation
has been observed, but many adolescents and young adults
with repaired tetralogy of Fallot have regurgitant fractions
exceeding 40% to 50%, with RV end-diastolic dimensions of
more than 150 ml per m2 (normal 75 ml per m2) and RV
ejection fractions of less than 0.40. Gatzoulis et al. have noted
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that QRS prolongation (greater than 180 m per second)
relates to RV size and predicts malignant ventricular arrhythmias and sudden death after tetralogy of Fallot repair.847
Pulmonary valve replacement, usually with a homograft or
xenograft, has been performed with low risk,833 has been
shown to stabilize QRS duration, and, in conjunction with
cryoablation, has decreased the incidence of pre-existing
atrial and ventricular tachyarrhythmias.848 Pulmonary valve
replacement has also been found to result in reduction in
regurgitant fraction and RV end-diastolic volumes but little
change in RV ejection fraction.849,850
Most physicians would perform pulmonary valve replacement in patients with NYHA functional class II or III
symptoms and severe pulmonary regurgitation, but for
asymptomatic patients, the indications based on regurgitant
fraction, RV end-diastolic or end-systolic volume, and RV
ejection fraction remain unclear. Many would share the
concern that it may be unwise to wait until RV function
deteriorates, and that with pulmonary regurgitation, as with
AR, valve replacement (see Section 3.2.3.8) should be considered before irreversible damage to ventricular performance
occurs.851 That point has yet to be determined, however.
7. Surgical Considerations
Cardiac valve surgery began with off-pump trans-LV and/or
trans-left atrial commissurotomy performed to treat rheumatic MS in the early 1950s. Since this limited beginning,
valve surgery has flourished on the basis of advances in
surgical experience and technology, particularly the development of cardiopulmonary bypass, effective prosthetic valves,
and consistent intraoperative myocardial protection.
The availability of cardiopulmonary bypass allowed isolation of the heart from the circulation and the performance of
true open heart operations. Early valve operations were by
necessity conservative in nature and included open commissurotomy of the MV, simple repair of some types of MR and
AR, and decalcification of aortic valves.
The development of cardiac valve prostheses in the early
1960s expanded the spectrum of pathologies in patients with
valvular heart disease that could be treated surgically. Many
different designs for prosthetic heart valves were studied
experimentally and clinically during the 1970s, but by 1980,
the basic designs of the prostheses used today had been
established. Available heart valve prostheses can be grouped
into 2 major categories: mechanical valves and bioprostheses.
Mechanical valves have the advantage of structural stability
but the disadvantage of requiring anticoagulation with warfarin. Bioprostheses have the advantage of not requiring
anticoagulation with warfarin but the disadvantage of being
subject to time-related structural valve failure. All heart valve
replacement strategies are imperfect. An excellent review of
long-term durability and complications of valve prostheses
has been published by Grunkemeier et al.852 based on 265
clinical studies involving more than 61 000 prostheses and a
cumulative experience of 319 749 valve-years (Table 34).
After the development of cardiopulmonary bypass and
valvular prostheses, the next important technological advance
was development of cardioplegic myocardial protection, a
strategy that allows intraoperative protection of ventricular
function, even for patients with diffuse CAD, and at the same
time provides a favorable surgical field for complex valve
operations. As a result, abnormal preoperative myocardial
function is no longer the major predictor of risk for patients
undergoing valve surgery, and the overall in-hospital mortality and morbidity have decreased. In addition, effective
myocardial protection has made possible the most recent
technological trend in valve surgery, which is in the direction
of complex valve reparative procedures and the avoidance of
valve replacement.
7.1. American Association for Thoracic Surgery/
Society of Thoracic Surgeons Guidelines for
Clinical Reporting of Heart Valve Complications
In 1988, standards for defining and reporting complications
after heart valve operations were proposed by the Ad Hoc
Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity, a joint committee of the
American Association for Thoracic Surgery and the STS.853
These guidelines were revised in 1996.854,855 The complications determined to be of critical importance in the 1996
guidelines are summarized as follows:
• Structural valvular deterioration refers to any change in
function of an operated valve that results from an intrinsic
abnormality that causes stenosis or regurgitation.
• Nonstructural dysfunction is a composite category that
includes any abnormality that results in stenosis or regurgitation of the operated valve that is not intrinsic to the
valve itself, exclusive of thrombosis and infection. This
category includes inappropriate sizing, also called “valve
prosthesis-patient mismatch,”856 and tissue ingrowth
around the prosthesis that may cause a fixed stenosis or
inhibit valve motion, causing stenosis and/or regurgitation.
• Valve thrombosis is any thrombus, in the absence of
infection, attached to or near an operated valve that
occludes part of the blood flow path or interferes with
function of the valve.
• Embolism is any embolic event that occurs in the absence
of infection after the immediate perioperative period
(when anesthesia-induced unconsciousness is completely
reversed). This includes any new, temporary or permanent,
focal or global neurological deficit and peripheral embolic
event; emboli proven to consist of nonthrombotic material
are excluded.
• Bleeding event (formerly anticoagulant hemorrhage) is
any episode of major internal or external bleeding that
causes death, hospitalization, or permanent injury or requires transfusion. The complication “bleeding event”
applies to all patients, whether or not they are taking
anticoagulants or antiplatelet drugs.
• Operated valvular endocarditis is any infection that involves an operated valve. Morbidity associated with active
infection, such as valve thrombosis, thrombotic embolus,
bleeding event, or paravalvular leak, is included under this
category and not in other categories of morbidity.
The consequences of the above events include reoperation;
valve-related mortality; sudden unexpected, unexplained
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Table 34.
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Prosthetic Valve Clinical Studies
Type
Model
Position
Series
Valves
Valve-Years
Mechanical valves
Ball
Disc
Starr-Edwards
Björk-Shiley
Monostrut
5
2339
19 069
8
2524
20 928
Aortic
4
795
5954
Mitral
6
1330
8895
Aortic
4
4950
16 776
Mitral
3
4265
14 747
Aortic
8
1964
11 918
Mitral
4
638
3256
Aortic
2
185
1239
Mitral
1
103
716
Omnicarbon
Aortic
2
232
1280
Mitral
1
95
463
Ultracor
Aortic
1
225
751
Mitral
1
172
660
Medtronic Hall
Omniscience
Bileaflet
Aortic
Mitral
St. Jude
Carbomedics
Aortic
14
6813
33 379
Mitral
15
5636
28 456
Aortic
5
2252
7928
Mitral
4
1094
3917
Edwards Tekna
Aortic
4
1039
4586
Duromedics
Mitral
2
439
1903
Sorin Bicarbon
Aortic
1
163
408
95
37 253
187 230
Total mechanical
Biological valves
Porcine
Hancock I
Aortic
10
4118
30 260
Mitral
6
2014
16 282
Aortic
2
858
5010
Mitral
3
551
3086
Aortic
3
1265
2779
Mitral
3
779
2066
Carpentier-Edwards
Aortic
9
3069
15 962
Mitral
7
1977
12 632
Freestyle
Aortic
1
699
577
Bicor
Aortic
1
856
2317
Hancock II
Intact
Pericardial
C-E Perimount
Mitroflow
Homograft
Homograft
Mitral
1
137
510
Aortic
10
4865
23 027
Mitral
3
481
2179
Aortic
2
318
1800
Mitral
1
96
576
Aortic
Total biological
Total
8
2119
13 457
70
24 202
132 519
265
61 455
319 749
Modified with permission from Grunkemeier GL, Li HH, Naftel DC, et al. Long-term performance of heart valve prostheses. Curr Probl Cardiol 2000;25:73–154.852
death; cardiac death; total deaths; and permanent valverelated impairment854,855 in addition to cardiac-related symptoms such as dyspnea, fatigue, and angina. In addition, valve
prosthesis may produce hemolysis due either to the valve
itself or to associated perivalvular leak.
There is a wide range in the reported incidence of
complications with the same prosthetic valve and between
different valves.852 This is most likely due to variation
among series rather than to valve type and model.857 It has
been emphasized858 that these variations include factors
associated with patients (e.g., ventricular function, comorbidities), medical center (e.g., surgical variables, definitions of complications, thoroughness of follow-up), and
data analysis (e.g., influences of patient-related factors).857
In addition, published data represent only a small fraction
of valves implanted.852,858
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Many types of bias affect reported results,859 which might
be overcome with randomized trials; however, randomized
trials also have difficulties.860,861 The number of randomized
studies of prosthetic heart valves is small, and the majority of
those that have been reported are of insufficient size to add
importantly to the knowledge already obtained from careful
observational studies.
7.2. Aortic Valve Surgery
The types of operations available to treat aortic valve dysfunction include AVR with a mechanical or a bioprosthetic
valve, AVR with an allograft (homograft) valve, pulmonic
valve autotransplantation (Ross operation),153,822– 825,862 aortic
valve repair, and left ventricle–to– descending aorta shunt.
Each has specific advantages and disadvantages. Cardiopulmonary bypass is used in aortic valve operations, and these
procedures are usually performed through a median sternotomy incision, although partial sternotomy (minimally invasive incisions) is gaining acceptance. See Sections 3.1.7 and
3.2.3.8 for indications for AVR or repair in patients with AS
and AR.
7.2.1. Risks and Strategies in Aortic Valve Surgery
The voluntary STS database165 received reports regarding
9108 to 11 665 isolated AVRs per year during the years 1999
through 2004 (total of 62 834 operations). This voluntary
registry is not inclusive of national practice, but it represents
the best approximation currently available. Selected patientrelated descriptors were mean age 66 years, female gender
42%, and previous cardiac surgery 16.5%. Approximately
76% of patients had AS, and the mean LV ejection fraction
was 0.53. In-hospital mortality by year ranged from 2.9% to
3.6%, and the risk of permanent stroke was 1.5% to 1.8%.
Experienced centers have reported mortality rates for primary
isolated AVR of less than 1% to 2%, although the national
average in the STS database is 3% to 4%165 and is higher in
low-volume centers.166 During the 1999 to 2002 time frame,
the implantation of mechanical valves declined from 41% to
33% of total cases, with a corresponding increase in the
implantation of bioprostheses from 50% to 65%, whereas the
use of homografts was steady at approximately 2%.
The majority of patients undergoing AVR have other
cardiac lesions, most commonly CAD, and more complex
pathology has been associated with increased risk. Experienced centers have reported very little incremental risk
associated with combined pathology, but the mortality rates
for a combined AVR and CABG is 6% to 7%.165 Even
technical expertise does not negate the influence of cardiac
and noncardiac comorbidity associated with diffuse atherosclerosis or aneurysmal disease.
7.2.2. Mechanical Aortic Valve Prostheses
Designs of mechanical aortic valve prostheses currently
available in the United States include ball-and-cage valves,
single tilting disc prostheses, and bileaflet prostheses. Balland-cage valves have the disadvantage of noise and hemodynamic inefficiency and today are rarely used, although the
mechanical stability of ball-and-cage prostheses has been
excellent at follow-up intervals of more than 30 years.
Single-tilting disc valves currently available in the United
States are the Medtronic-Hall valve and the Omnicarbon
valve. These valves have superior hemodynamic efficiency to
ball-and-cage valves and have been structurally stable. The
most severe disadvantage of the single-disc design is severe
hemodynamic compromise if disc thrombosis or immobility
occurs.
The most common mechanical valve design used in the
aortic position is the bileaflet valve, with versions available in
the United States being manufactured by St. Jude, CarboMedics, ATS Medical, and On-X. The bileaflet valves are relatively quiet, appear to be mechanically stable, and are
relatively hemodynamically efficient. The operation for implantation of mechanical prostheses is standard, as is the
surgery for reoperation when that is needed. The disadvantages of mechanical valves are the need to take warfarin for
anticoagulation to prevent thromboembolism, the risk of
bleeding complications, the risk of thromboembolism despite
warfarin therapy, endocarditis, and hemodynamic inefficiency
in smaller sizes. Also, the structural stability of mechanical
valves does not eliminate the possibility of reoperation for
other indications such as valve thrombosis, tissue ingrowth
and valve dysfunction, periprosthetic leak, endocarditis,
symptomatic patient-prosthesis mismatch, and multiple
bleeding episodes secondary to warfarin therapy.
7.2.2.1. Antithrombotic Therapy for Patients With Aortic
Mechanical Heart Valves
After mechanical AVR, the goal of antithrombotic therapy is
usually to achieve an INR of 2.5 to 3.5 for the first 3 months
after surgery and 2.0 to 3.0 beyond that time (see Section 9.2).
Low-dose aspirin (75 to 100 mg per day) is also indicated in
addition to warfarin,808 as discussed in Section 9.2.1. At that
level of anticoagulation, the risk of significant hemorrhage
appears to be 1% to 2% per year. Although the goal of
mechanical and materials engineering has been to produce a
mechanical valve that does not require anticoagulation with
warfarin, that goal has not yet been achieved. Trials diminishing or eliminating anticoagulation with warfarin or substituting platelet inhibitors for warfarin have so far noted a high
rate of thromboembolism.
7.2.3. Stented and Nonstented Heterografts
7.2.3.1. Aortic Valve Replacement With Stented Heterografts
The most commonly used aortic valve prostheses in the
United States today are stented heterografts that are constructed with bovine pericardial tissue or porcine aortic valve
tissue arranged on a cloth and metal frame. These valves have
the advantages of a low thromboembolism rate without
warfarin, a simple and standard implantation technique, a
standard reoperation risk, a low risk of catastrophic valve
failure, and widespread availability in many valve sizes. The
disadvantages of stented heterografts are structural valve
deterioration, imperfect hemodynamic efficiency, a standard
risk of prosthetic valve endocarditis, and a low (0.7% per
year) but present risk of thromboembolism without warfarin
anticoagulation. Stented pericardial heterografts have better
hemodynamic performance than porcine heterografts, especially in smaller sizes (less than 21 mm).863– 866 In a random-
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Table 35.
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e615
Structural Valve Deterioration of Bioprosthetic Valves
Number of
Valves
Mean
Follow-Up,
y
AVR
Jamieson et al.,
1988867
5.6
572
Cohn et al.,
1989868
6.0
Jones et al.,
1990869
Freedom From
SVD, %
MVR
Time of
SVD
Estimate, y
Age, y
AVR
MVR
509
10
30–59
81 ⫾ 4
78 ⫾ 5
Greater than 60
91 ⫾ 3
71 ⫾ 9
971
708
15
40 or less
41– 69
70 or greater
68 ⫾ 9
86 ⫾ 2
94 ⫾ 3
68 ⫾ 10
84 ⫾ 13
84 ⫾ 10
Hancock porcine bioprosthesis (includes
146 combined AVR ⫹ MVR procedures)
8.3
610
528
10
Less than 40
40 – 49
50 –59
60 – 69
46 ⫾ 7
60
79
92 ⫾ 2
47 ⫾ 8
48 ⫾ 8
61
80 ⫾ 6
Hancock or Carpentier-Edwards porcine
bioprosthesis (includes 88 combined AVR
⫹ MVR procedures)
Burdon et al.,
1992872
7.3
857
793
15
16 –39
40 – 49
50 –59
60 – 69
Greater than 70
33 ⫾ 7
54 ⫾ 10
57 ⫾ 6
73 ⫾ 6
93 ⫾ 3
37 ⫾ 6
38 ⫾ 12
38 ⫾ 5
61 ⫾ 15
62 ⫾ 6
Hancock I and Hancock modified orifice
porcine bioprosthesis
Burr et al.,
1992873
—
574
500
7
Less than 65
65– 69
70 –79
80 or greater
94 ⫾ 1
98 ⫾ 1
100
100
88 ⫾ 2
90 ⫾ 4
95 ⫾ 3
100
Carpentier-Edwards standard porcine
bioprosthesis (similar results were
obtained with Carpentier-Edwards supraannular porcine bioprosthesis)
13–15
Less than 65
62 ⫾ 8
65–69
98 ⫾ 3
63 ⫾ 8
70–79
95 ⫾ 5
74 ⫾ 19
Author, Year
Comments
Carpentier-Edwards standard porcine
bioprosthesis
37 ⫾ 7
80 or greater
100
—
Pelletier et al.,
1992874
7.0
451
547
10
Less than 45
45–54
55– 64
65 or greater
70
84
84
93
55
64
69
95
Carpentier-Edwards standard (302 AVR, 324
MVR) improved annulus (97 AVR, 135
MVR), supra-annular (52 AVR, 88 MVR)
porcine bioprostheses (includes 121
combined AVR ⫹ MVR and 5 combined
MVR ⫹ TVR procedures)
Cosgrove et al.,
1995875
7.8
310
—
10
Less than 65
65 or greater
88.6
95.5
—
—
Carpentier-Edwards pericardial aortic
bioprosthesis
Pelletier et al.,
1995876
4.5
416
—
10
Less than 60
60 – 69
70 or greater
86.3
95.3
100
—
—
—
Carpentier-Edwards pericardial aortic
bioprosthesis
Cohn et al.,
1998877
6.1
843
—
10
50 or less
51– 69
70 or greater
57
77
96
—
—
—
Hancock modified orifice porcine aortic
valve
15
50 or less
16
—
51–69
54
—
Banbury et al.,
2001168
Jamieson et al.,
2001879
12
6.2
70 or greater
87
—
267
—
15
45
55
65
75
58
70
82
91
—
—
—
—
Carpentier-Edwards pericardial aortic
bioprosthesis
836
332
12
51– 60
61–70
Greater than 70
90 ⫾ 3
97 ⫾ 3
Medtronic Intact porcine bioprosthesis
92 ⫾ 3
96 ⫾ 2
98 ⫾ 1
AVR indicates aortic valve replacement; MVR, mitral valve replacement; SVD, structural valve deterioration; and TVR, tricuspid valve replacement.
ized trial comparing stented porcine xenografts and stented
pericardial valves,866 the reduced pressure gradients with the
pericardial valve translated into greater reduction in LV mass at
a mean 1.2-year follow-up period after AVR.
The first-generation stented heterografts (porcine heterografts) exhibited a freedom from structural valve deterioration of approximately 40% by 18 postoperative years. How-
ever, the rate of structural valve deterioration is agerelated,168,867– 880 being increased for younger patients, and in
patients less than 40 years of age, approximately half of
porcine valves fail by 10 years (Table 35). Bovine pericardial
valves appear to have a lower rate of structural valve
deterioration, with 15-year data indicating that 77% of valves
in surviving patients of all ages are functioning without
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explantation, and among patients undergoing primary AVR at
an age greater than 65 years, fewer than 10% underwent valve
explantation by 15 postoperative years.168,876 The reported
rate of structural valve deterioration for second-generation
porcine valves appears so far to be equivalent to that of
stented bovine valves.
7.2.3.2. Aortic Valve Replacement With Stentless Heterografts
Stentless heterografts are valves constructed from porcine
aortic valves that use a smaller amount of cloth for stabilization, sewing, and tissue ingrowth than a full cloth-metal stent.
The major goal of stentless heterografts is to achieve enhanced
hemodynamic efficiency relative to stented valves.881– 886 The
long-term importance of hemodynamic efficiency of prosthetic heart valves is currently a subject of investigation and
disagreement. The argument favoring the use of stentless
valves is that stented valves of any kind are at least partially
stenotic (particularly in small sizes) and that even small
postoperative gradients may lead to incomplete LV mass regression postoperatively,883,885– 887 which will, in turn, lead to impaired long-term survival and symptom status. Some randomized and nonrandomized but comparative studies885– 887 have
reported lower transvalvular gradients and more consistent
regression of LV mass after AVR when stentless valves are used
than with stented prostheses, whereas other studies show no
differences.888,889 In addition, the long-term importance of LV
mass regression is not clear.
One nonrandomized study reported improved postoperative survival with stentless than with stented porcine bioprostheses.890 However, in the several randomized trials comparing stented and stentless valves, there has been no difference
in patient outcomes at 1 to 3 years after surgery.886 – 889 It is
clear that the combination of large and active patients and
small aortic valve prostheses can lead to high transprosthetic
gradients (particularly with exercise) and symptoms related to
patient-prosthesis mismatch.856 However, the importance of
small transvalvular gradients is as yet unclear. Stentless
heterografts have the disadvantage that their implantation is
more complex than that for stented valves, and their longterm outcomes are unknown. There is a low incidence (7% to
10%) of early mild AR in some series,883,884,886 which may
progress with time, but it is uncertain whether this differs
from the experience with some stented bioprostheses.856,883,884 Observational studies with 8- to 10-year followup891 appear to show a low risk of structural valve deterioration with stentless heterografts, and the hope is that improved
hemodynamic design will lead to improved longevity. Time
will tell. Stentless valves are implanted with techniques
similar to those used for aortic valve homografts, but they
have the advantage of increased availability compared with
aortic valve homografts.
7.2.4. Aortic Valve Homografts
Aortic valve allografts (homografts) have been used for AVR
since early in the cardiac surgical era,892 but the rapid failure
rate of early homografts (30% structural valve deterioration
by 10 years) and the complex implantation techniques required limited their use. The use of homografts has been
revived by cryopreservation techniques that appear to diminish the rate of structural valve deterioration.169,171 Homografts
may be implanted as a “free hand” valve in the subcoronary
position; as a “mini-root” replacement, during which the
valve is implanted within the native root cylinder; and as a
full root replacement, during which the native aortic root is
removed and entirely replaced with the homograft aortic root,
the coronary arteries being reimplanted into the homograft.
All these operations are more complex than the implantation
of standard mechanical valves or stented heterografts. Total
aortic root replacement is currently the most common homograft implantation strategy.
It had been hoped that aortic valve homografts would outlast
heterografts, particularly in young patients, but to date, longterm data do not support this view. One possible advantage of
homografts is in the avoidance of early endocarditis and in the
treatment of aortic valve endocarditis,893– 896 particularly complex aortic root endocarditis, although the literature does not
demonstrate the superiority of any single prosthesis in these
situations.852,897–900 The risk of thromboembolism is very low
after homograft implantation, and hemodynamic efficiency is
excellent even in small sizes. The biggest disadvantage of
homografts is that reoperation after homograft AVR is more
difficult than reoperation after placement of standard prostheses,
because the entire homograft may become severely calcified. In
a randomized trial comparing homografts and stentless bioprosthetic valves, there was no difference in hemodynamics or
patient outcomes at 1 year after operation.901,902 As with stentless
bioprostheses, AR may develop, and there is an increased
likelihood of need for reoperation in patients under the age of 40
years.903
7.2.5. Pulmonic Valve Autotransplantation
Pulmonic valve autotransplantation (Ross operation) is an
operation developed in an attempt to provide a permanent
biological aortic valve prosthesis using the pulmonic
valve.153,822,823,825,862 In this operation, the pulmonic valve is
excised and used to replace the aortic valve either as a
subcoronary implantation or as a full aortic root replacement,
while the pulmonic valve is then replaced with an alternative
prosthesis, usually a pulmonic homograft. This operation has
been performed in small numbers, and long-term follow-up
studies have been inconsistent, which makes analysis of
long-term advantages and disadvantages difficult. The known
advantages of the procedure are that the autograft may grow
in children, warfarin is not required, there is a low incidence
of thromboembolism, the autograft is a hemodynamically
efficient valve, and the incidence of endocarditis is low.904
The disadvantage of pulmonic autotransplantation is that the
operation is much more complex than standard AVR and in
most series has been associated with at least some increase in
in-hospital mortality. There is also an incidence of early
aortic valve failure based on technical considerations or
dilatation of the aortic root, and the homograft used to replace
the pulmonic valve is also subject to failure, sometimes early,
within a few years of operation.862 Small, short-term randomized and nonrandomized comparisons of pulmonary autografts and aortic homografts have demonstrated no definite
advantage of either in adults in terms of hemodynamics and
patient outcome.905–907 Deterioration of the pulmonary homograft also offsets potential advantages of the autograft.
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Table 36. Probability of Death Due to Any Cause, Any Valve-Related Complications, and Individual Valve-Related Complications
15 Years After Randomization in the Veterans Affairs Cooperative Study on Valvular Heart Disease
Aortic Valve
Mitral Valve
Mechanical
(n ⴝ 198)
Porcine
(n ⴝ 196)
p
Mechanical
(n ⴝ 88)
Porcine
(n ⴝ 93)
p
Death due to any cause
66 ⫾ 3
79 ⫾ 3
0.02
81 ⫾ 4
79 ⫾ 4
0.30
Any valve-related complications
65 ⫾ 4
66 ⫾ 5
0.26
73 ⫾ 6
81 ⫾ 5
0.56
Systemic embolism
18 ⫾ 4
18 ⫾ 4
0.66
18 ⫾ 5
22 ⫾ 5
0.96
Bleeding
51 ⫾ 4
30 ⫾ 4
⬍0.001
53 ⫾ 7
31 ⫾ 6
0.01
Endocarditis
7⫾2
15 ⫾ 5
0.45
11 ⫾ 4
17 ⫾ 5
0.37
Valve thrombosis
2⫾1
1⫾1
0.33
1⫾1
1⫾1
0.95
Perivalvular regurgitation
8⫾2
2⫾1
0.09
17 ⫾ 5
7⫾4
0.05
10 ⫾ 3
29 ⫾ 5
0.004
25 ⫾ 6
50 ⫾ 8
0.15
0⫾0
23 ⫾ 5
⬍0.001
5⫾4
44 ⫾ 8
⬍0.001
Event
Reoperation
Structural valve failure
Values are actuarial percentages plus/minus standard error. Note: p values are for differences between mechanical and porcine valves. Data are from
Hammermeister K, Sethi GK, Henderson WG, et al. Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the
Veterans Affairs randomized trial. J Am Coll Cardiol 2000;36:1152– 8.174 Reprinted with permission.
7.2.6. Aortic Valve Repair
Multiple strategies for aortic valve repair have been explored,
some successfully. Aortic valve repair by decalcifying stenotic calcific aortic valves was used in the preprosthesis era
but abandoned because of recalcification and restenosis.
Revival of its use with modern myocardial protection and
decalcification techniques still is associated with a high rate
of restenosis. Repair of rheumatic aortic valves has, in
general, not been successful over time. In contrast, repair of
insufficient bicuspid aortic valves in the adult has been increasingly successful at limited numbers of centers.827,908,909 Among
the advantages of this strategy are the lack of need for
anticoagulation, a low thromboembolic risk, a low endocarditis risk, a hemodynamically efficient valve, and a
straightforward reoperation, if needed. The disadvantages
are lack of uniform applicability, lack of widespread
experience with surgical techniques, and the need for
reoperation. Long-term data are limited, but the risk of
reoperation appears to be about 15% by 10 postoperative
years. Although late calcification of these repaired valves
has to be considered likely given enough time, calcification
may be delayed in some patients with repaired bicuspid
valves, who may avoid reoperation for decades.
Much progress has been made in the repair of aortic valves
rendered insufficient by aortic root pathology.364,910 –915 When
an aortic root aneurysm exists, the operation to restore
competence to the aortic valve involves resecting the aorta
and resuspending the valve in association with a Dacron graft
that is used to replace the aorta. Advantages of this strategy
include avoidance of warfarin, a low thromboembolic risk, a
very efficient valve, and what appears to be a low risk of
prosthetic valve endocarditis. The disadvantages are, again,
limited applicability in the setting of intrinsic leaflet pathology and the high level of surgical expertise and experience
required.
7.2.7. Left Ventricle–to–Descending Aorta Shunt
In situations involving pathologies that make standard AVR
operations particularly risky, such as multiple previous operations, severe aortic calcification, and previous radiation therapy,
a left ventricle–to– descending thoracic aortic shunt using a
Dacron graft containing a valve can be an effective alternative
treatment.916 This procedure is performed through a left thoracotomy with or without cardiopulmonary bypass. A valved
conduit is connected to the LV apex via a metal connector and
then anastomosed to the descending intrathoracic aorta. Favorable short-term outcomes have been reported, but the long-term
hemodynamics results and complication rate associated with this
strategy are currently unknown.
7.2.8. Comparative Trials and Selection of Aortic Valve
Prostheses
Two randomized trials have compared outcomes for patients
receiving mechanical and bioprosthetic valves in the aortic
position, the Edinburgh Heart Valve Trial (1975–1979)917
and the Veterans Affairs Cooperative Study on Valvular
Heart Disease (1979 –1982).174,918 Both compared the BjorkShiley tilting-disc valve with first-generation porcine heterografts. In the Veterans Affairs trial, 15-year survival rates
were superior for patients with mechanical valves (34%)
compared with those with bioprostheses (21%) in the aortic
position (p ⫽ 0.02), but 20-year survival rates were no
different in the Edinburgh trial. As expected, bleeding rates
were significantly higher for patients with mechanical valves,
and structural valve deterioration and reoperation rates were
higher for patients with bioprostheses in both trials.174,917,918
The long-term results of the Veterans Affairs Cooperative
Study174 are shown in Table 36.
Despite the randomized design of these trials and the
apparent slight advantage for patients receiving mechanical
prostheses, the trend in the United States has been away from
mechanical prostheses and towards biological valves for
multiple reasons.
• Current bioprostheses appear to have lower rates of structural
valve deterioration than those used during the randomized
trials that involved first-generation bioprostheses. Reoperation rates for patients over 65 years of age are particularly low
with modern stented bioprostheses (Table 35).
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• The risks of reoperation have continued to decrease since
these trials were completed, particularly the risk of a first
reoperation.
• Patients undergoing AVR today represent an older population than those studied in the randomized trials.
• Young patients undergoing aortic valve surgery are often
reluctant to accept warfarin therapy and the activity constraints associated with anticoagulants.
• There are some nonrandomized but relatively large comparative trials that have shown apparent survival benefit
for patients receiving bioprostheses, particularly for those
over the age of 65 years.919
On the basis of these considerations, most patients over 65
years of age receive a bioprosthesis. There are no data
involving large patient numbers that clearly show long-term
advantages for one type of aortic valve operation over another
or for any individual prosthesis over another.
At many major valve surgery centers, the age threshold for
the use of bioprosthetic valves in the aortic position has
decreased to well below 65 years in those patients who do not
wish to take anticoagulation. The decision requires full discussion with the patient, with the understanding that there is a
higher chance of the need for reoperation with a bioprosthesis.
In the previous 1998 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease, mechanical
valves were recommended (Class IIa) in patients with endstage renal failure, especially those undergoing chronic dialysis, because of the concern of accelerated calcification of
bioprosthetic valves. Subsequent retropsective studies919a
have demonstrated no significant difference in outcome of
such patients treated with mechanical prostheses versus
bioprostheses. The current writing committee has made no
specific recommendations for valve selection in dialysis
patients, but notes the difficulties in maintaining anticoagulation in these patients.
Selection among biological valve operations is based on logic
and opinion rather than consistently defined differences and
outcomes. Surgeon experience is important, because there are no
long-term data justifying the use of operations that increase
perioperative risk. The most common biological valve used is a
stented heterograft because of its easy implantation, the ease of
reoperation, the extensive data defining its late outcomes, and
the lack of data supporting the use of more complex strategies.
Although it had been hoped that homografts would have an
improved failure rate relative to stented heterografts, at this
point, data do not support that view. A stentless allograft or
homografts are a good choice for patients with small aortic root
sizes at risk for patient-prosthesis mismatch.856,863– 865 Stentless
heterografts have been effective in the short term, but the extent
of their advantage is unclear in regard to valve efficiency, and
long-term failure rates are not known.886,889,920 Current data
noting a 20% failure rate by 10 postoperative years do not
indicate improved long-term outcomes compared with stented
bioprostheses. Pulmonic valve autotransplantation is used by
some to allow growth of the autograft in children. Its use in
adults has been limited by some increase in operative risk and
data indicating a reoperation rate of approximately 20% by 10
postoperative years.
7.2.9. Major Criteria for Aortic Valve Selection
Class I
1. A mechanical prosthesis is recommended for AVR in
patients with a mechanical valve in the mitral or
tricuspid position. (Level of Evidence: C)
2. A bioprosthesis is recommended for AVR in patients of
any age who will not take warfarin or who have major
medical contraindications to warfarin therapy. (Level
of Evidence: C)
Class IIa
1. Patient preference is a reasonable consideration in the
selection of aortic valve operation and valve prosthesis.
A mechanical prosthesis is reasonable for AVR in
patients under 65 years of age who do not have a
contraindication to anticoagulation. A bioprosthesis is
reasonable for AVR in patients under 65 years of age
who elect to receive this valve for lifestyle considerations after detailed discussions of the risks of anticoagulation versus the likelihood that a second AVR may
be necessary in the future. (Level of Evidence: C)
2. A bioprosthesis is reasonable for AVR in patients aged
65 years or older without risk factors for thromboembolism. (Level of Evidence: C)
3. Aortic valve re-replacement with a homograft is reasonable for patients with active prosthetic valve endocarditis. (Level of Evidence: C)
Class IIb
1. A bioprosthesis might be considered for AVR in a
woman of childbearing age (see Sections 5.7 and 5.8).
(Level of Evidence: C)
7.3. Mitral Valve Surgery
MV surgery began with valve-conserving operations for
rheumatic MS and expanded to treat a variety of pathologies
once prosthetic valve replacement became available. Today,
valve-conserving operations have become more common and
are used to treat a variety of pathologies. Analysis of the
outcomes after MV surgery is complex. Those outcomes are
affected not only by the valve-coronary pathology treated but
also by LV function, cardiac rhythm, and surgeon experience.
Operations currently available to treat MV dysfunction include closed mitral commissurotomy, replacement with a
mechanical prosthesis, replacement with a bioprosthesis,
replacement with an MV homograft or Ross-type autograft,
and a variety of reparative MV procedures.
The surgical approaches to MV surgery are varied. Closed
or “off-pump” mitral commissurotomy can be performed
either percutaneously with a balloon catheter or surgically
through a left thoracotomy (see Sections 3.4.8 and 3.4.9). The
standard approach for MV replacement or complex repair is
use of a median sternotomy with cardiopulmonary bypass;
however, many alternative incisions are now used, including
partial sternotomy and small right thoracotomy access, strategies described as “minimally invasive.” Video-assisted and
robotic-assisted MV surgery are becoming more feasible, and
standard outcomes have been described for small numbers of
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selected patients undergoing surgery at centers that specialize
in these alternative surgical strategies.
When the MV is replaced, an attempt is made to preserve
at least part of the subvalvular apparatus, that is, the chordae
tendineae connecting the papillary muscles with the valve
annulus. Experimental and clinical data show that long-term
LV function may benefit by this strategy.
7.3.1. Mitral Valve Repair
MV surgery began with conservative operations for rheumatic
MS; within the last 20 years, conservative operations to treat MR
have been developed and popularized to treat degenerative and
functional MV disease, as well as some patients with MV
endocarditis. The outcomes of MV repair must be analyzed according to the pathologies treated rather than the operation alone.
7.3.1.1. Myxomatous Mitral Valve
Class I
1. MV repair is recommended when anatomically possible
for patients with severe degenerative MR who fulfill
clinical indications, and patients should be referred to
surgeons who are expert in repair. (Level of Evidence: B)
2. Patients who have undergone successful MV repair
should continue to receive antibiotics as indicated for
endocarditis prophylaxis. (Level of Evidence: C)
3. Patients who have undergone successful MV repair
and have chronic or paroxysmal atrial fibrillation
should continue to receive long-term anticoagulation
with warfarin. (Level of Evidence: B)
4. Patients who have undergone successful MV repair
should undergo 2D and Doppler echocardiography
before discharge or at the first postoperative outpatient
visit. (Level of Evidence: C)
5. Tricuspid valve repair is beneficial for severe TR in
patients with MV disease that requires MV surgery.
(Level of Evidence: B)
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experienced surgeons can repair the MV using strategies that
involve removal of unsupported leaflet structures, transfer of
chordae,467,468 or the use of artificial chordae to support
unstable areas of the leaflet, the sliding of supported areas of
the leaflet to cover the MV orifice, and stabilization of the
size and shape of the MV annulus with an artificial
ring.529,530,545,568 –573 When possible, MV repair is the treatment of choice for degenerative valve disease, because
patients in sinus rhythm do not need warfarin, the thromboembolism rate is low, valve efficiency and hemodynamics are
good, there is little adverse effect on LV function, the risk of
endocarditis is low, and the long-term survival rate is favorable compared with MV replacement (see Section 3.6.4).
Concomitant tricuspid valve repair should be performed
when there is severe TR or mild-to-moderate TR and tricuspid annular dilatation (see Section 3.7.4.3 and Section 3.8.3).
In patients presenting for MV repair with chronic atrial
fibrillation, a concomitant surgical procedure to eliminate atrial
fibrillation may prevent future embolic events by restoring
normal sinus rhythm.608 – 614 The decision to proceed with a
surgical procedure to eliminate atrial fibrillation should be made
based on the age and health of the patient, as well as the surgical
expertise, because this procedure may add to the morbidity of
the operation (see Section 3.6.4.2.4).
The likelihood of a successful MV repair is related to the
extent of the MV dysfunction (with isolated posterior leaflet
dysfunction being the most favorable condition); the presence
and extent of calcification; the amount of pliable, noncalcified
valve tissue; and surgeon experience. Recurrent MR after repair
may occur with time, but in favorable situations, more than 90%
of valves are still functioning well after 10 years.529,530
7.3.1.2. Rheumatic Heart Disease
Class I
Class IIa
1. Percutaneous or surgical MV commissurotomy is indicated when anatomically possible for treatment of severe
MS, when clinically indicated. (Level of Evidence: C)
1. Oral anticoagulation is reasonable for the first 3
months after MV repair. (Level of Evidence: C)
2. Long-term treatment with low-dose aspirin (75 to 100
mg per day) is reasonable in patients who have undergone successful MV repair and remain in sinus
rhythm. (Level of Evidence: C)
3. Tricuspid annuloplasty is reasonable for mild TR in
patients undergoing MV repair when there is pulmonary hypertension or tricuspid annular dilatation.
(Level of Evidence: C)
Rheumatic MR is inconsistently reparable, and the long-term
outcomes after repair are not as good as for valve repair for
degenerative MV disease. Rheumatic pathology often leads to
leaflet and chordal scarring, which restricts the leaflet motion,
and leaflet scarring may be progressive after repair. Rheumatic MS that is not associated with severe chordal fusion or
shortening or with calcification may be treated with either
percutaneous or open mitral commissurotomy with a high
degree of long-term success. Clinical indications for these
procedures are discussed in Section 3.4.8.
Class IIb
7.3.1.3. Ischemic Mitral Valve Disease
By definition, all patients with ischemic MR have significant
CAD that usually has a significant effect on long-term
survival. The pathology of ischemic MR has multiple subgroups, with the most common situation being functional
MR, in which the valve leaflets are structurally normal, but
LV chamber enlargement and papillary muscle displacement
tether the MV via the chordal attachments and prevent leaflet
coaptation.616 – 623 When functional MR is severe, it may be
1. In patients with MR and a history of atrial fibrillation, a
Maze procedure may be considered at the time of MV
repair. (Level of Evidence: B)
Myxomatous MV disease produces MR based on rupture or
elongation of chordae tendineae, valve leaflet instability,
annulus dilatation, or multiple causes that result in excessive
MV leaflet motion. In the majority of these conditions,
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corrected by placement of an annuloplasty ring that decreases
the annular circumference, shortens the intertrigonal distance,
reduces the septal-lateral (anterior-posterior) annular diameter, and restores the geometry of the annulus, thereby allowing the MV leaflets to coapt.624 – 627,633– 642 This strategy
acutely decreases or eliminates MR, but because the fundamental abnormality is related to LV function, the late survival
rate of these patients is relatively low compared with patients
with other MV pathologies, and the recurrence rate of mitral
dysfunction is higher. For patients with moderate functional
MR, it is not yet clear whether MV repair improves
outcomes.
Patients with ischemic MV disease who have anatomic MR
based on infarction or rupture of the papillary muscles benefit
from either mitral repair or MV replacement. Papillary muscle
rupture often produces severe MR and hemodynamic decompensation, which is an indication for emergency surgery.
7.3.1.4. Mitral Valve Endocarditis
With increased surgical experience in mitral reparative techniques, MV endocarditis has become more consistently treatable with repair.760 –762 There appears to be a low risk of
recurrent infection, and in experienced hands, it is often
possible to avoid the need for an MV prosthesis (see Section
4.6.1). Surgery, however, must not be delayed until extensive
valve disruption has occurred.
7.3.2. Mitral Valve Prostheses (Mechanical
or Bioprostheses)
Mechanical Prostheses: Ball-and-cage valves, single-tilting
disc valves, and bileaflet prostheses are available MV prostheses. Ball-and-cage valves have been effective but can
cause some degree of outflow tract obstruction by projecting
into the LV outflow tract, a problem not present with bileaflet
or disc valves. Most studies have shown that the thromboembolism risk is greater for patients with mechanical MV
prostheses than for patients with aortic valves, even when
adjusted for the presence of atrial fibrillation. Thus, anticoagulation for patients with mechanical MV prostheses is
maintained at an INR of 2.5 to 3.5 indefinitely.
Bioprostheses: Both porcine heterografts and bovine pericardial heterografts are available in the United States for MV
replacement. Porcine heterografts have been followed up for
longer intervals, but limited data appear to show a slower rate
of structural valve deterioration for second-generation porcine heterografts and bovine pericardial valves.921,922 The
failure rate of mitral heterografts appears to be higher than
that for aortic heterografts (Table 35). For example, in the VA
Cooperative Study, 29% of aortic valve and 50% of mitral
porcine heterografts needed reoperation by 15 postoperative
years (Table 36).174
7.3.2.1. Selection of a Mitral Valve Prosthesis
Class I
1. A bioprosthesis is indicated for MV replacement in a
patient who will not take warfarin, is incapable of
taking warfarin, or has a clear contraindication to
warfarin therapy. (Level of Evidence: C)
Class IIa
1. A mechanical prosthesis is reasonable for MV replacement in patients under 65 years of age with longstanding atrial fibrillation. (Level of Evidence: C)
2. A bioprosthesis is reasonable for MV replacement in
patients 65 years of age or older. (Level of Evidence: C)
3. A bioprosthesis is reasonable for MV replacement in
patients under 65 years of age in sinus rhythm who
elect to receive this valve for lifestyle considerations
after detailed discussions of the risks of anticoagulation
versus the likelihood that a second MV replacement
may be necessary in the future. (Level of Evidence: C)
The STS National Cardiac Surgery Database165 indicates that
the numbers of MV reparative procedures are increasing
relative to MV replacement. For isolated MV operations
during the years 2000 through 2004, valve repairs numbered
2335, 2755, 3779, 3978, and 3712, respectively, compared
with 4215, 4141, 4517, 4145, and 3579 MV replacement
operations, respectively. Mortality rates were 1.5% to 2.0%
for repair versus 5.4% to 6.4% for MV replacement. Among
patients receiving a MV replacement, more patients received
mechanical valves than bioprostheses. Medicare data indicate
that the mortality for isolated MV replacement in patients older
than 65 years is 14.1%, which increases to 20.5% in low-volume
centers.167 When MV pathology is combined with CAD, the
risks of surgery increase. For the same 5 years noted above, an
average of 3637 patients per year underwent MV repair combined with CABG,165 with mortality rates ranging from 7% to
8.7%, and 2814 patients per year underwent MV replacement
plus CABG, with mortality rates in excess of 11%. The majority
of patients in this group received bioprostheses. The selection of
a valve is a multifactorial decision.
7.3.2.2. Choice of Mitral Valve Operation
MV repair should be able to be achieved by experienced
surgeons for the majority of patients with degenerative MV
disease and ischemic valve disease, and patients should be
referred to surgeons expert in repair. For patients with rheumatic
MV disease and endocarditis, repair may be more difficult.
For patients undergoing MV replacement, preservation of
the chordal apparatus preserves LV function and enhances
postoperative survival compared with MV replacement in
which the apparatus is disrupted,570,579 –582 as discussed in
Section 3.6.4.1. In the randomized trials, there was no
difference in survival rate based on valve type; however, the
failure rate of bioprostheses has been higher in the mitral than
in the aortic position (Table 35), which adds impetus to the
use of mechanical prostheses in younger patients.
The availability of surgical ablation procedures for atrial
fibrillation offers the possibility of converting the patient to
sinus rhythm and avoiding anticoagulation after MV repair or
replacement with a bioprosthesis.608 – 614 If patients can be
maintained in sinus rhythm, the advantage of a bioprosthesis
is enhanced. For patients with a history of atrial fibrillation
who are undergoing MV repair, a Maze-type procedure
results in sinus rhythm in 75% to 90% of cases by 6
postoperative months, with long-term data indicating sustained results up to 8 years and reduced risk of stroke.611,614
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The effect of ablation of atrial fibrillation for patients with
multivalve disease or valve disease combined with CAD is
not known.
7.4. Tricuspid Valve Surgery
Class I
1. Severe TR in the setting of surgery for multivalvular
disease should be corrected. (Level of Evidence: C)
Class IIa
1. Tricuspid annuloplasty is reasonable for mild TR in
patients undergoing MV surgery when there is pulmonary hypertension or tricuspid annular dilatation.
(Level of Evidence: C)
The most common cause of TR is dilatation of the tricuspid
valve annulus caused by pulmonary hypertension. The tricuspid leaflets are usually normal, and tricuspid valve annuloplasty usually corrects or improves the situation. Severe TR
should be treated with annuloplasty during operations for
multivalvular disease (see Sections 3.7.4.3 and 3.8.3). Other
causes of TR include rheumatic valvular disease, endocarditis, leaflet scarring due to inflammatory conditions, and
adherence of tricuspid valve structures to transtricuspid pacing wires. When leaflet anatomy is severely abnormal, tricuspid valve replacement may be needed, but this situation is not
common. There are no data clearly showing the advantage of
one type of tricuspid prosthesis over another.
7.5. Valve Selection for Women of Childbearing Age
There is no ideal valve prosthesis for women of childbearing
age who might wish to become pregnant (see detailed
discussion in Section 5.8). Bioprostheses may be subject to
premature heterograft or homograft failure. Because mechanical valves require anticoagulation, there is an increased risk
of fetal abnormalities and mortality, and there may be an
increased risk of maternal complications, including thromboembolism. Discussion with the patient concerning the risk of
the prosthesis is important (see Section 5.8.4).
8. Intraoperative Assessment
Class I
1. Intraoperative transesophageal echocardiography is
recommended for valve repair surgery. (Level of Evidence: B)
2. Intraoperative transesophageal echocardiography is
recommended for valve replacement surgery with a
stentless xenograft, homograft, or autograft valve.
(Level of Evidence: B)
3. Intraoperative transesophageal echocardiography is
recommended for valve surgery for infective endocarditis. (Level of Evidence: B)
Class IIa
1. Intraoperative transesophageal echocardiography is
reasonable for all patients undergoing cardiac valve
surgery. (Level of Evidence: C)
e621
Detailed and comprehensive evaluation of valve lesions during cardiac surgery has become possible and common since the
development of transesophageal echocardiography. This includes confirmation of the preoperative diagnosis and associated
pathology, provision of additional detail and depth about the
severity and mechanism of valve dysfunction, detection of
previously undiagnosed conditions, and evaluation of the surgical result in the operating room, which makes possible the
immediate correction of detected problems. Studies have documented the impact of intraoperative transesophageal echocardiography on valve surgery, with changes in the operative plan
based on transesophageal echocardiography findings reported in
11% to 14% of cases and detection of problems with surgical
procedure and subsequent need to return to cardiopulmonary
bypass reported in 2% to 6%.923–926 Other important aspects of
transesophageal echocardiography during valve surgery include
assessment of ventricular function and detection of intracardiac
air and aortic dissection.
Currently, the application of transesophageal echocardiography during valve surgery varies a great deal from institution
to institution. Availability of equipment and expertise are
important factors in determining this application, and the
committee recognizes that such resources may vary. Although controlled, randomized trials substantiating the benefit
of intraoperative transesophageal echocardiography during
valve surgery have not been performed, there are many
nonrandomized studies, case series, and significant expert
experience that support its utility in this setting.
Intraoperative transesophageal echocardiography is especially important during valve repair surgery. Examination
before cardiopulmonary bypass provides insight into the
mechanism of valve dysfunction and therefore facilitates
surgical planning. More importantly, intraoperative transesophageal echocardiography allows immediate assessment
of the repair after cardiopulmonary bypass. Intraoperative
transesophageal echocardiography during valve replacement
surgery with a stented prosthetic valve is also useful, although
there will be a lower rate of problems detected after cardiopulmonary bypass. Valve replacement with a stentless xenograft, homograft, or autograft valve will have a higher
likelihood of technical problems during surgery, and therefore, transesophageal echocardiography is virtually essential
in this setting because it is currently the best way to assess
valve function intraoperatively. Because of the potential for
multiple valve involvement and associated lesions such as
abscesses and fistulas, transesophageal echocardiography
should also be performed during valve surgery for acute
infective endocarditis. Patients undergoing valve surgery may
have other indications for intraoperative transesophageal
echocardiography, such as severely decreased LV function or
hemodynamic instability. The committee recommends that
institutions performing valve surgery establish consistent and
credible intraoperative echocardiography programs with
knowledgeable echocardiographers committed to and capable
of providing accurate anatomic and functional information
relevant to valve operations. Such services should be available during surgery to facilitate evaluation of unexpected
difficulties. Although transesophageal echocardiography is
generally a safe procedure when properly performed in
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appropriate patients, there are risks to its performance.927
Thus, preoperative screening for risk factors and the obtainment of informed consent should be a routine part of every
intraoperative transesophageal study.
A physician trained in transesophageal echocardiography,
be it a cardiologist, cardiac anesthesiologist, or cardiac
surgeon, must perform the intraoperative transesophageal
echocardiogram.928 Intraoperative transesophageal echocardiography studies may vary considerably in duration depending
on complexity of the information being sought. For instance,
evaluation of complex MV repair before cardiopulmonary
bypass often requires a detailed, time-consuming study,
whereas evaluation of severe calcific AS tends to be more
limited and less time consuming. The physician must have
sufficient time to obtain comprehensive images as needed to
ensure an accurate diagnosis, facilitate perioperative decision
making, and enhance patient outcome. Echocardiography
technicians or sonographers should not manipulate an intraoperative transesophageal echocardiography probe, nor
should they be put in a position to provide patient outcomerelated interpretations or advice.
Several means of evaluating patients during valve surgery
other than transesophageal echocardiography are available,
but they are not a substitute for the direct anatomic information provided by transesophageal echocardiography. Measurements of intracardiac pressures and flows may be made
with central venous and pulmonary artery catheters or by
direct transmyocardial needle insertion after exposure of the
heart. A surface echocardiographic transducer may be placed
in a sterile sheath and passed onto the surgical field for
application directly to the heart or the ascending aorta, a
technique called epicardial and epiaortic echocardiography,
as a useful alternative in patients in whom transesophageal
probe insertion cannot be performed or is contrain
dicated.929 Information gained from all these techniques may
be complementary and may be combined to obtain a more
comprehensive characterization of the lesion.
In general, whenever possible, the decision to treat a valve
lesion surgically should be made before the patient is in the
operating room. Specifically, in cases of MR, intraoperative
assessment of the degree of MR can be misleading owing to
the unloading effects of general anesthesia. In a patient having
surgery for another reason (e.g., CABG or another valve),
intraoperative transesophageal echocardiography occasionally might provide the basis for this decision, but it should not
replace preoperative assessment of the valve lesion with
transthoracic echocardiography or catheterization. Intraoperative transesophageal echocardiography can confirm the preoperative diagnosis, provide additional details that may guide
the surgical procedure, and help to guide management of
hemodynamics. It remains the best means of immediately
assessing the technical results of the surgical procedure in the
operating room.
8.1. Specific Valve Lesions
8.1.1. Aortic Stenosis
The surgical treatment for AS is almost always replacement
with a prosthetic valve. Intraoperative transesophageal echocardiography926 can be used to measure the size of the aortic
annulus to facilitate selection of the proper size prosthesis and
also, in patients with bicuspid valves, to provide information
regarding aortic root dilatation and need for repair (see
Section 3.3). After implantation of the prosthesis, transesophageal echocardiography can detect technical problems such as
paravalvular regurgitation or abnormal leaflet motion. Stentless prostheses and homografts are more prone to distortion,
with resulting regurgitation, and should be assessed in the
operating room by transesophageal echocardiography. Excessive cardiac vent return or arterial pulsatility during cardiopulmonary bypass may be indications of significant AR after
AVR. Transesophageal echocardiography can be used to
confirm the diagnosis. Transesophageal imaging can also
determine the adequacy of coronary reimplantation by both
direct imaging of the coronaries and assessment of LV
function.
8.1.2. Aortic Regurgitation
Although the severity and significance of AR is partially
dependent on afterload and may be difficult to quantify with
transesophageal echocardiography during surgery, transesophageal echocardiography usually provides highresolution images of the aortic valve and is quite helpful in
determining the mechanism and cause of regurgitation. The
amount of cardiac vent return and arterial pulsatility during
cardiopulmonary bypass may provide some indication of
severity as well. The surgical treatment for AR is usually
replacement with a prosthetic valve, but valve repair is
sometimes attempted. Measurements of the size of the aortic
root may direct the surgeon toward root replacement rather
than simple replacement of the regurgitant valve. Intraoperative transesophageal echocardiography should be used to
evaluate the results of an aortic valve repair immediately after
cardiopulmonary bypass. Considerations of the transesophageal echocardiography evaluation of a prosthetic aortic valve
after cardiopulmonary bypass are similar to those for AS.
8.1.3. Mitral Stenosis
Most adult patients presenting for surgery for MS have
rheumatic heart disease, although extremely severe mitral
annular calcification on occasion may cause significant stenosis. Intraoperative transesophageal echocardiography can
provide anatomic information, especially about the subvalvar
structures, that is difficult to directly visualize through the left
atriotomy and is critical in deciding whether to replace or
repair a rheumatic valve. The presence of thrombus in the left
atrium may be detected with transesophageal echocardiography as well. Intraoperative transesophageal echocardiography
should be used to evaluate the results of a mitral commissurotomy immediately after cardiopulmonary bypass, primarily
to detect significant MR. Residual stenosis may be difficult to
quantify by echocardiography. For example, the pressure
half-time method to measure MV area is probably not
accurate immediately after a commissurotomy and should not
be relied on solely to assess adequacy of the commissurotomy.403 Although the Doppler-derived transmitral pressure
gradient is easily obtained and may help in this situation, this
may underestimate MS severity in the presence of a low
cardiac output. The transmitral gradient can be measured by
direct transduction of LV and left atrial pressures if there is
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concern about residual stenosis. If a prosthetic MV is implanted, transesophageal echocardiography can detect technical problems such as paravalvular regurgitation or abnormal
leaflet motion. Small, insignificant central and paravalvular
leaks are commonly seen immediately after cardiopulmonary
bypass and should not be a cause for concern.930
8.1.4. Mitral Regurgitation
Patients undergoing surgery for MR usually have either
myxomatous degeneration (MVP) or ischemic heart disease.
Other less common causes of MR that requires surgery are
infective endocarditis and rheumatic heart disease. Because
the change in hemodynamic loading conditions caused by
general anesthesia during surgery may lead to underestimation of the severity of MR by intraoperative transesophageal
echocardiography,632,633,931,932 the decision to operate is best
made before surgery based on the symptoms and preoperative
testing. If intraoperative evaluation is required as a precursor
to MV repair or replacement, the operator must attempt to
reproduce both preoperative afterload and preload conditions.
Intraoperative transesophageal echocardiography may provide additional information about the mechanism of regurgitation and may be helpful to direct the decision whether to
repair or replace the valve.923,924,933 Thus, intraoperative
transesophageal imaging should be used whenever a repair is
contemplated. Intraoperative transesophageal echocardiography should also be used to evaluate the results of an MV
repair immediately after cardiopulmonary bypass to assess
for residual MR, systolic anterior motion of the valve leaflets,
and restriction of mitral opening with stenosis. Representative
loading conditions may need to be created with volume or
vasopressors to fully assess the adequacy of the MV repair
immediately after the patient is weaned from cardiopulmonary bypass. If a prosthetic MV is implanted, transesophageal
echocardiography can detect technical problems such as
paravalvular regurgitation or abnormal leaflet motion. Small,
insignificant central or paravalvular leaks are commonly
observed immediately after cardiopulmonary bypass, and
should not be a cause for concern.930 It is possible to injure
the left circumflex coronary artery or tether a cusp of the
aortic valve with a suture placed in the mitral annulus.
Therefore, assessment of LV function and examination of the
aortic valve and adjacent structures should always be performed with transesophageal echocardiography after MV
surgery.
8.1.5. Tricuspid Regurgitation
TR that requires surgery is most often secondary to annular
dilation with right-sided heart enlargement, which is usually
corrected with tricuspid valve repair. Secondary TR can
change with the hemodynamic loading conditions. Therefore,
the decision to address TR surgically is best made before
induction of general anesthesia and surgery whenever possible (see Sections 3.7.4 and 3.8). Intraoperative transesophageal echocardiography can provide detailed information
about the mechanism of TR that is useful in deciding whether
to repair or replace a valve and should be used when a repair
is contemplated. Intraoperative transesophageal echocardiography should be used to evaluate the results of a tricuspid
valve repair immediately after cardiopulmonary bypass to
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assess for residual regurgitation and restriction of the tricuspid valve opening with stenosis. If a prosthetic tricuspid valve
is implanted, transesophageal echocardiography can detect
technical problems such as paravalvular regurgitation or
abnormal leaflet motion.
8.1.6. Tricuspid Stenosis
Tricuspid stenosis that requires surgery is most commonly
due to rheumatic heart disease and is treated by replacement
of the valve with a prosthesis. As with other prosthetic valve
replacements, transesophageal echocardiography can detect
technical problems such as paravalvular leaks or immobile
leaflets after cardiopulmonary bypass and allow correction of
the problem during the same operation.
8.1.7. Pulmonic Valve Lesions
In adults, the pulmonic valve is much less commonly operated on than the aortic, mitral, and tricuspid valves. It is often
difficult to image with transesophageal echocardiography,
and decisions to operate on the pulmonic valve should be
made based on preoperative studies such as transthoracic
echocardiography or cardiac magnetic resonance whenever
possible. Pulmonic valve lesions are treated surgically by
prosthetic valve replacement in adults, and transesophageal
echocardiography may be able to detect technical problems
such as paravalvular leaks or immobile leaflets in the operating room after cardiopulmonary bypass. When the issue of
pulmonic stenosis is raised during heart surgery, direct
measurement of RV and pulmonary artery pressures with
catheters or needles can be very helpful.
8.2. Specific Clinical Scenarios
8.2.1. Previously Undetected Aortic Stenosis
During CABG
CAD and AS are commonly present in the same patient. On
occasion, intraoperative transesophageal echocardiography
detects previously undiagnosed AS in a patient undergoing
CABG surgery. Indications for AVR in this situation are the
same as described in Section 10.4. If the AS is moderate or
severe, AVR is indicated. Controversy persists as to whether
AVR should be performed during CABG surgery when mild
AS is present. There may be difficulty in accurately assessing
the severity of AS with intraoperative transesophageal echocardiography by Doppler techniques in some patients. Confirmation of the severity of the gradient may be obtained after
the heart is exposed by direct transduction of the LV and aortic
pressures. Epicardial echocardiography may also provide additional, helpful information.
8.2.2. Previously Undetected Mitral Regurgitation
During CABG
On occasion, intraoperative transesophageal echocardiography may detect previously undiagnosed, significant MR in a
patient undergoing CABG surgery (see Sections 3.6.5,
7.3.1.3, and 10.5). An examination of the valve with transesophageal echocardiography should be performed to determine the mechanism of the MR. If there is a structural
abnormality such as prolapse or flail, the valve should be
repaired or replaced. Ischemic MR due to LV remodeling and
apical tenting of the leaflets can be very dynamic and may
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Table 37.
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October 7, 2008
Recommendations for Antithrombotic Therapy in Patients With Prosthetic Heart Valves
Aspirin
(75–100 mg)
Warfarin
(INR 2.0–3.0)
Warfarin
(INR 2.5–3.5)
No
Warfarin
Mechanical prosthetic valves
AVR–low risk
Less than 3 months
Greater than 3 months
Class I
Class I
Class I
Class I
Class IIa
AVR–high risk
Class I
Class I
MVR
Class I
Class I
Biological prosthetic valves
AVR–low risk
Less than 3 months
Class I
Greater than 3 months
Class I
AVR–high risk
Class IIa
Class IIb
Class IIa
Class I
Class I
Less than 3 months
Class I
Class IIa
Greater than 3 months
Class I
MVR–low risk
MVR–high risk
Class I
Class IIa
Class I
Depending on patients’ clinical status, antithrombotic therapy must be individualized (see special situations in text). In patients receiving warfarin, aspirin is
recommended in virtually all situations. Risk factors: atrial fibrillation, left ventricular dysfunction, previous thromboembolism, and hypercoagulable condition.
International normalized ratio (INR) should be maintained between 2.5 and 3.5 for aortic disc valves and Starr-Edwards valves. Modified with permission from McAnulty
JH, Rahimtoola SH. Antithrombotic therapy in valvular heart disease. In: Schlant R, Alexander RW, editors. Hurst’s The Heart. New York, NY: McGraw-Hill,
1998:1867–74.934
AVR indicates aortic valve replacement; and MVR, mitral valve replacement.
respond to acute hemodynamic management in the operating
room by increasing or decreasing in severity according to
changes in afterload and LV size. Patients with severe
ischemic MR should undergo MV repair or MV replacement
(see Sections 3.6.5 and 7.3.1.3). Controversy exists as to
whether patients having CABG surgery with moderate or
mild MR should undergo MV repair as well. However, the
hemodynamic effects of drugs received during surgery often
lessen the severity of the MR, and mild intraoperative MR
may increase postoperatively. Hence, it is reasonable to
perform MV repair when there is moderate and, in many
cases, mild MR detected on intraoperative transesophageal
echocardiography.
9.2. Antithrombotic Therapy (Table 37)
Class I
9.1.1. Infective Endocarditis
All patients with prosthetic valves need appropriate antibiotics for prophylaxis against infective endocarditis (see Section
2.3.1).
1. After AVR with bileaflet mechanical or Medtronic Hall
prostheses, in patients with no risk factors,* warfarin
is indicated to achieve an INR of 2.0 to 3.0. If the
patient has risk factors, warfarin is indicated to
achieve an INR of 2.5 to 3.5. (Level of Evidence: B)
2. After AVR with Starr-Edwards valves or mechanical
disc valves (other than Medtronic Hall prostheses), in
patients with no risk factors,* warfarin is indicated to
achieve an INR of 2.5 to 3.5. (Level of Evidence: B)
3. After MV replacement with any mechanical valve,
warfarin is indicated to achieve an INR of 2.5 to 3.5.
(Level of Evidence: C)
4. After AVR or MV replacement with a bioprosthesis
and no risk factors,* aspirin is indicated at 75 to 100
mg per day. (Level of Evidence: C)
5. After AVR with a bioprosthesis and risk factors,*
warfarin is indicated to achieve an INR of 2.0 to 3.0.
(Level of Evidence: C)
6. After MV replacement with a bioprosthesis and risk
factors,* warfarin is indicated to achieve an INR of 2.0 to
3.0. (Level of Evidence: C)
7. For those patients who are unable to take warfarin
after MV replacement or AVR, aspirin is indicated in
a dose of 75 to 325 mg per day. (Level of Evidence: B)
9.1.2. Recurrence of Rheumatic Carditis
Patients with rheumatic heart disease continue to need antibiotics as prophylaxis against recurrence of rheumatic carditis
(see Section 2.3.2).
*Risk factors include atrial fibrillation, previous thromboembolism, LV
dysfunction, and hypercoagulable condition.
9. Management of Patients with Prosthetic
Heart Valves
The results of valve surgery with regard to survival, functional class, valve function, and complications are dependent
on patient related factors, cardiac function, type of surgery,
type of prosthesis, and medical comorbidities.857
9.1. Antibiotic Prophylaxis
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8. The addition of aspirin 75 to 100 mg once daily to
therapeutic warfarin is recommended for all patients
with mechanical heart valves and those patients with
biological valves who have risk factors.* (Level of
Evidence: B)
Class IIa
1. During the first 3 months after AVR with a mechanical
prosthesis, it is reasonable to give warfarin to achieve
an INR of 2.5 to 3.5. (Level of Evidence: C)
2. During the first 3 months after AVR or MV replacement with a bioprosthesis, in patients with no risk
factors,* it is reasonable to give warfarin to achieve an
INR of 2.0 to 3.0. (Level of Evidence: C)
Class IIb
1. In high-risk patients with prosthetic heart valves in
whom aspirin cannot be used, it may be reasonable
to give clopidogrel (75 mg per day) or warfarin to
achieve an INR of 3.5 to 4.5. (Level of Evidence: C)
All patients with mechanical valves require warfarin therapy, as indicated in Table 37.934 Aspirin is recommended
for all patients with prosthetic heart valves: aspirin alone
in patients with bioprostheses and no risk factors, and
aspirin combined with warfarin in patients with mechanical heart valves and high-risk patients with bioprostheses.
In high-risk patients who cannot take aspirin, the addition
of clopidogrel to warfarin therapy should be considered. Even
with the use of warfarin, risk of thromboemboli is 1% to 2%
per year,171,172,174,214,852,935 but the risk is considerably higher
without treatment with warfarin.936 The risk of a clinical
thromboembolism is on average 0.7% per year in patients
with biological valves in sinus rhythm; this figure is derived
from several studies in which the majority of patients were
not undergoing therapy with warfarin.171,172,174,214,937 Almost
all studies have shown that the risk of embolism is greater
with a valve in the mitral position (mechanical or biological)
than with one in the aortic position.172,178,852,936,938 With either
type of prosthesis or valve location, the risk of emboli is
probably higher in the first few days and months after valve
insertion,937 before the valve is fully endothelialized.804
It is frequently difficult to maintain a patient at a fixed or
relatively fixed level of anticoagulation owing to changes in
absorption of medication, the effects of various foods and
medications, and changes in liver function. Therefore, in
clinical practice, the patient’s anticoagulation level is maintained within a certain therapeutic range. This can be optimized through a program of patient education and close
surveillance by an experienced healthcare professional.
9.2.1. Mechanical Valves
All patients with mechanical valves require anticoagulation.
For mechanical prostheses in the aortic position, the INR with
warfarin therapy should be maintained between 2.0 and 3.0
for bileaflet valves and Medtronic Hall valves and between
2.5 and 3.5 for other disc valves and Starr-Edwards valves;
for prostheses in the mitral position, the INR should be
maintained between 2.5 and 3.5 for all mechanical
valves.172,174,852,938 –947 There is a difference of opinion regard-
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ing the Starr-Edwards valve in the aortic position, with the
minority opinion recommending that INR be maintained
between 2.0 and 3.0. The recommendation for higher INR
values in the mitral position is based on the greater risk of
thromboembolic complications with mechanical valves in the
mitral position171,852,936,938,942,943,946,947 and the greater risk of
bleeding at higher INRs.946 In patients with aortic mechanical
prosthesis who are at higher risk of thromboembolic complications, INR should be maintained at 2.5 to 3.5, and the
addition of aspirin should be considered (see below). These
include patients with atrial fibrillation, previous thromboembolism, and a hypercoagulable state. Many would also include patients with severe LV dysfunction in this higher-risk
group.948 Some prostheses are thought to be more thrombogenic than others (particularly the tilting-disc valves), and a
case could be made for increasing the INR to between 3 and
4.5; however, this level of anticoagulation is associated with
a considerably increased risk of bleeding.938,949
The addition of low-dose aspirin (75 to 100 mg per day) to
warfarin therapy (INR 2.0 to 3.5) not only further decreases
the risk of thromboembolism808,946,950 –953 but also decreases
mortality due to other cardiovascular diseases. A slight
increase in the risk of bleeding with this combination should
be kept in mind.950,954 The risk of gastrointestinal irritation
and hemorrhage with aspirin is dose dependent over the range
of 100 to 1000 mg per day, and the antiplatelet effects are
independent of dose over this range.955,956 There are no data
in patients with prosthetic heart valves receiving warfarin and
aspirin in doses of 100 to 325 mg per day. Doses of 500 to
1000 mg per day clearly increase the risk of bleeding.957–959
The addition of aspirin (75 to 100 mg per day) to warfarin
should be strongly considered unless there is a contraindication to the use of aspirin (i.e., bleeding or aspirin intolerance).
This combination is particularly appropriate in patients who
have had an embolus while undergoing warfarin therapy,
those with known vascular disease, and those who are known
to be particularly hypercoagulable. As an example, such
combination therapy is recommended by a committee concerning the use of antithrombotic therapy in women during
pregnancy.807 The method of anticoagulation in pregnant
patients is controversial and is discussed in Section 5.8.
Thromboembolic risk is increased early after insertion of
the prosthetic heart valve. The use of UFH early after
prosthetic valve replacement, before warfarin achieves therapeutic levels, is controversial. Many centers start UFH as
soon as the risk of increased surgical bleeding is reduced
(usually within 24 to 48 h), with maintenance of aPTT
between 55 and 70 s. After an overlap of UFH and warfarin
for 3 to 5 days, UFH is discontinued when an INR of 2.0 to
3.0 is achieved. In some patients, achievement of therapeutic
INR must be delayed several days after surgery because of
mitigating complications.
9.2.2. Biological Valves
Because of an increased risk of thromboemboli during the
first 3 months after implantation of a biological prosthetic
valve, anticoagulation with warfarin is often used, especially when the valve is in the mitral position,937 although
most centers use only aspirin for biological valves in the
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aortic position. The risk is particularly high in the first few
days after surgery, and many centers start UFH as soon as
the risk of increased surgical bleeding is reduced (usually
within 24 to 48 h), with maintenance of aPPT between 55
and 70 seconds. After an overlap of UFH and warfarin for
3 to 5 days, UFH may be discontinued when an INR of 2.0
to 3.0 is achieved. After 3 months, the tissue valve can be
treated like native valve disease, and warfarin can be
discontinued in more than two thirds of patients with
biological valves.174,937,960 In the remaining patients with
associated risk factors for thromboembolism, such as atrial
fibrillation, previous thromboembolism, or hypercoagulable condition, lifelong warfarin therapy is indicated to
achieve an INR of 2.0 to 3.0. Many would also recommend
continuing anticoagulation in patients with severe LV
dysfunction (ejection fraction less than 0.30).948
9.2.3. Embolic Events During Adequate Antithrombotic
Therapy
In the patient who has a definite embolic episode while
undergoing adequate antithrombotic therapy, the dosage of
antithrombotic therapy should be increased, when clinically
safe, as follows:
• Warfarin, INR 2.0 to 3.0: warfarin dose increased to
achieve INR of 2.5 to 3.5
• Warfarin, INR 2.5 to 3.5: warfarin dose may need to be
increased to achieve INR of 3.5 to 4.5
• Not taking aspirin: aspirin 75 to 100 mg per day should be
initiated
• Warfarin plus aspirin 75 to 100 mg per day: aspirin dose
may also need to be increased to 325 mg per day if the
higher dose of warfarin is not achieving the desired clinical
result
• Aspirin alone: aspirin dose may need to be increased to
325 mg per day, clopidogrel 75 mg per day per day added,
and/or warfarin added.
9.2.4. Excessive Anticoagulation
In most patients with INR above the therapeutic range,
excessive anticoagulation can be managed by withholding
warfarin and monitoring the level of anticoagulation with
serial INR determinations.804 Excessive anticoagulation (INR
greater than 5) greatly increases the risk of hemorrhage.
However, rapid decreases in INR that lead to INR falling
below the therapeutic level increase the risk of thromboembolism. Patients with prosthetic heart valves with an INR of
5 to 10 who are not bleeding can be treated by withholding
warfarin and administering 1 to 2.5 mg of oral vitamin K1
(phytonadione).804,961 The INR should be determined after
24 h and subsequently as needed. Warfarin therapy is restarted and adjusted dose appropriately to ensure that the INR
is in the therapeutic range. In emergency situations, the use of
fresh frozen plasma is preferable to high-dose vitamin K1,962
especially parenteral vitamin K1, because use of the latter
increases the risk of overcorrection to a hypercoagulable state.
Low-dose intravenous vitamin K (1 mg) appears safe in this
situation.963
9.2.5. Bridging Therapy in Patients With Mechanical
Valves Who Require Interruption of Warfarin
Therapy for Noncardiac Surgery, Invasive Procedures,
or Dental Care
Class I
1. In patients at low risk of thrombosis, defined as those
with a bileaflet mechanical AVR with no risk factors,*
it is recommended that warfarin be stopped 48 to 72 h
before the procedure (so the INR falls to less than 1.5)
and restarted within 24 h after the procedure. Heparin
is usually unnecessary. (Level of Evidence: B)
2. In patients at high risk of thrombosis, defined as those
with any mechanical MV replacement or a mechanical
AVR with any risk factor, therapeutic doses of intravenous UFH should be started when the INR falls
below 2.0 (typically 48 h before surgery), stopped 4 to
6 h before the procedure, restarted as early after
surgery as bleeding stability allows, and continued
until the INR is again therapeutic with warfarin therapy. (Level of Evidence: B)
Class IIa
1. It is reasonable to give fresh frozen plasma to patients
with mechanical valves who require interruption of warfarin therapy for emergency noncardiac surgery, invasive
procedures, or dental care. Fresh frozen plasma is preferable to high-dose vitamin K1. (Level of Evidence: B)
Class IIb
1. In patients at high risk of thrombosis, therapeutic doses
of subcutaneous UFH (15 000 U every 12 h) or LMWH
(100 U per kg every 12 h) may be considered during the
period of a subtherapeutic INR. (Level of Evidence: B)
Class III
1. In patients with mechanical valves who require interruption of warfarin therapy for noncardiac surgery,
invasive procedures, or dental care, high-dose vitamin
K1 should not be given routinely, because this may create
a hypercoagulable condition. (Level of Evidence: B)
The risk of increased bleeding during a procedure performed
with a patient receiving antithrombotic therapy has to be
weighed against the increased risk of a thromboembolism
caused by stopping the therapy. The risk of stopping warfarin
can be estimated and is relatively slight if the drug is withheld
for only a few days. As an example, in a worst-case scenario
(e.g., a patient with a mechanical prosthesis with previous
thromboemboli), the risk of a thromboembolism when the
patient is not taking warfarin is 10% to 20% per year. Thus,
if therapy were stopped for 3 days, the risk of an embolus
would be 0.08% to 0.16%. There are theoretical concerns that
stopping the drug and then reinstituting it might result in
hypercoagulability or that there might be a thrombotic “rebound.” An increase in markers for activation of thrombosis
*Risk factors: atrial fibrillation, previous thromboembolism, LV dysfunction, hypercoagulable conditions, older-generation thrombogenic valves,
mechanical tricuspid valves, or more than 1 mechanical valve.
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with abrupt discontinuation of warfarin therapy has been
observed,964 but it is not clear whether the clinical risk of
thromboembolism increases.965 In addition, when warfarin
therapy is reinstituted, there are theoretical concerns about a
hypercoagulable state caused by suppression of protein C and
protein S before the drug affects the thrombotic factors.
Although these risks are only hypothetical, individuals at very
high risk should be treated with heparin until INR returns to
the desired range.
Management of antithrombotic therapy must be individualized, but some generalizations apply.934 Antithrombotic therapy
should not be stopped for procedures in which bleeding is
unlikely or would be inconsequential if it occurred, for example,
surgery on the skin, dental cleaning, or simple treatment for
dental caries. Eye surgery, particularly for cataracts or glaucoma,
is usually associated with very little bleeding and thus is
frequently performed without alterations to antithrombotic treatment. When bleeding is likely or its potential consequences are
severe, antithrombotic treatment should be altered. If a patient is
taking aspirin, it should be discontinued 1 week before the
procedure and restarted as soon as it is considered safe by the
surgeon or dentist. Clopidogrel should be stopped at least 5 days
before the procedure.
Spyropoulos et al. performed a retrospective analysis of
costs and clinical outcomes associated with LMWH for
perioperative bridging in patients receiving long-term oral
anticoagulant therapy.966 The mean total healthcare costs in
the perioperative period were significantly lower (by $13
114) in patients receiving long-term oral anticoagulant therapy with LMWH than in those receiving it with UFH for an
elective surgical procedure. The cost savings associated with
LMWH use were accomplished through the avoidance or
minimization of inpatient stays and no increase in the overall
rate of clinical adverse events in the postoperative period.966
For patients with a bileaflet mechanical aortic valve and no
risk factors, warfarin should be stopped before the procedure
so that the INR is less than 1.5 (which is often 48 to 72 h after
warfarin is discontinued)934,967 and restarted within 24 h after
a procedure. Admission to the hospital or a delay in discharge
to give heparin is usually unnecessary.965,968 –970 Patients at
high risk of thrombosis include all patients with mechanical
mitral or tricuspid valve replacements and patients with an
AVR and any risk factors. Such risk factors include atrial
fibrillation, previous thromboembolism, hypercoagulable
condition, older-generation mechanical valves, LV dysfunction (ejection fraction less than 0.30), or more than 1
mechanical valve.971–973 When UFH is used, it should be
started when INR falls below 2.0 (i.e., 48 h before surgery)
and stopped 4 to 6 h before the procedure. UFH should be
restarted as early after surgery as bleeding stability allows,
and the aPTT should be maintained at 55 to 70 s until
warfarin is therapeutic. LMWH is attractive because it is
more easily used outside the hospital. One study of bridging
therapy for interruption of warfarin included 215 patients
with mechanical valves. In the total group of 650 patients, the
risk of thromboembolism (including possible events) was
0.62%, with 95% confidence intervals of 0.17% to 1.57%.
Major bleeding occurred in 0.95% (0.34% to 2.00%).974
However, concerns about the use of LMWH for mechanical
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valves persists, and package inserts continue to list a warning
for this use of these medications.815
High-dose vitamin K1 should not be given routinely,
because this may create a hypercoagulable condition. For
emergency situations, fresh frozen plasma is preferable to
high-dose vitamin K1 (see Section 9.2.4).
9.2.6. Antithrombotic Therapy in Patients Who Need Cardiac Catheterization/Angiography
In an emergency or semiurgent situation, cardiac catheterization
can be performed in a patient taking warfarin, but preferably, the
drug should be stopped, on average, 72 h before the procedure so
that INR is less than 1.5 (see above). The drug should be
restarted as soon as the procedure is completed. This is true for
patients with biological valves who are receiving antithrombotic
therapy and for those with mechanical valves. If a patient has
more than 1 risk factor that predisposes to thromboembolism,
heparin should be started when INR falls below 2.0 and should
be continued when warfarin is restarted. After an overlap of 3 to
5 days, heparin may be discontinued when the desired INR is
achieved. If the catheterization procedure is to include a transseptal puncture (especially in a patient who has not had previous
opening of the pericardium), patients should be removed from
all antithrombotic therapy, and INR should be less than 1.2; the
same is true if an LV puncture is to be performed.975 In patients
who are to undergo transseptal or LV puncture and are receiving
heparin therapy, heparin should be discontinued 4 to 6 h before
the procedure(s) and can be restarted without a bolus more than
4 h after the sheath in the peripheral vessel has been removed.
9.2.7. Thrombosis of Prosthetic Heart Valves
Class I
1. Transthoracic and Doppler echocardiography is indicated in patients with suspected prosthetic valve
thrombosis to assess hemodynamic severity. (Level of
Evidence: B)
2. Transesophageal echocardiography and/or fluoroscopy
is indicated in patients with suspected valve thrombosis
to assess valve motion and clot burden. (Level of
Evidence: B)
Class IIa
1. Emergency operation is reasonable for patients with a
thrombosed left-sided prosthetic valve and NYHA functional class III–IV symptoms. (Level of Evidence: C)
2. Emergency operation is reasonable for patients with a
thrombosed left-sided prosthetic valve and a large clot
burden. (Level of Evidence: C)
3. Fibrinolytic therapy is reasonable for thrombosed
right-sided prosthetic heart valves with NYHA functional class III–IV symptoms or a large clot burden.
(Level of Evidence: C)
Class IIb
1. Fibrinolytic therapy may be considered as a first-line
therapy for patients with a thrombosed left-sided
prosthetic valve, NYHA functional class I–II symptoms, and a small clot burden. (Level of Evidence: B)
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2. Fibrinolytic therapy may be considered as a first-line
therapy for patients with a thrombosed left-sided
prosthetic valve, NYHA functional class III–IV symptoms, and a small clot burden if surgery is high risk or
not available. (Level of Evidence: B)
3. Fibrinolytic therapy may be considered for patients
with an obstructed, thrombosed left-sided prosthetic
valve who have NYHA functional class II–IV symptoms and a large clot burden if emergency surgery is
high risk or not available. (Level of Evidence: C)
4. Intravenous UFH as an alternative to fibrinolytic therapy may be considered for patients with a thrombosed
valve who are in NYHA functional class I–II and have
a small clot burden. (Level of Evidence: C)
sidered. An alternative in patients who remain hemodynamically
stable is to convert intravenous UFH to combined therapy with
subcutaneous UFH (twice daily to an aPTT of 55 to 80 s) and
warfarin (INR 2.5 to 3.5) for 1 to 3 months on an outpatient basis
to allow for endogenous fibrinolysis.985 If intravenous UFH,
fibrinolytic therapy, combined UFH/fibrinolytic therapy, or
combined UFH/warfarin is successful, warfarin doses should be
increased so that INR is between 3.0 and 4.0 (approximately 3.5)
for prosthetic aortic valves and between 3.5 and 4.5 (approximately 4.0) for prosthetic MVs. These patients should also
receive low-dose aspirin.
Thrombosis of mechanical tricuspid valve prostheses may
be treated with fibrinolytic therapy, although experience with
this is limited.987,988
Obstruction of prosthetic heart valves may be caused by
thrombus formation, pannus ingrowth, or a combination of
both. The cause may be difficult to determine and requires
knowledge of the clinical presentation and findings on echocardiography, including transesophageal echocardiography.976 –981 If the prosthesis is obstructed by pannus, fibrinolytic therapy will be ineffective, and the valve needs to be
replaced. Fibrinolytic therapy for a left-sided prosthetic valve
obstructed by thrombus is associated with significant risks
(cerebral emboli in 12% to 15% of cases) and is often
ineffective. Fibrinolytic therapy in such patients is reserved
for those in whom surgical intervention carries a high risk and
those with contraindications to surgery.976 –980,982–986
In patients with a “small clot” who are in NYHA functional
class I or II, treatment with short-term intravenous UFH
therapy or continuous infusion of fibrinolytic therapy may be
considered.976 –980,982–986 The size threshold for this recommendation is difficult to define because of the lack of large
cohort studies and differing thresholds from small studies
(ranging from 5 to 10 mm, as determined by transesophageal
echocardiography), below which intravenous UFH or fibrinolytic therapy is safe and effective.976 –978,984 The risk associated with clot size is a continuous function, with 1 study
showing an odds ratio of 2.41 per 1-cm2 increment.978 Data
support the use of urokinase, streptokinase, or recombinant
tissue plasminogen activator as the fibrinolytic agents in this
situation. Factors that identify patients at risk for adverse
outcomes of fibrinolytic therapy include active internal bleeding, history of hemorrhagic stroke, recent cranial trauma of
neoplasm, diabetic hemorrhagic retinopathy, large thrombi,
mobile thrombi, hypertension (greater than 200 over 120 mm
Hg), hypotension or shock, and NYHA functional class
III–IV symptoms. If fibrinolytic therapy is successful, it
should be followed by intravenous UFH until warfarin
achieves an INR of 3.0 to 4.0 for aortic prosthetic valves and
3.5 to 4.5 for mitral prosthetic valves. If partially successful,
fibrinolytic therapy may be followed by a combination of
subcutaneous UFH twice daily (to achieve an aPTT of 55 to
80 s) plus warfarin (INR 2.5 to 3.5) for a 3-month period.985
Patients with small thrombi who receive intravenous UFH as
first-line therapy and who do not respond successfully may
receive a trial of continuous-infusion fibrinolytic therapy. If
fibrinolytic therapy is unsuccessful or there is an increased risk
associated with fibrinolytic therapy, reoperation should be con-
9.3. Follow-Up Visits
Class I
1. For patients with prosthetic heart valves, a history,
physical examination, and appropriate tests should be
performed at the first postoperative outpatient evaluation, 2 to 4 weeks after hospital discharge. This should
include a transthoracic Doppler echocardiogram if a
baseline echocardiogram was not obtained before hospital discharge. (Level of Evidence: C)
2. For patients with prosthetic heart valves, routine
follow-up visits should be conducted annually, with
earlier re-evaluations (with echocardiography) if there
is a change in clinical status. (Level of Evidence: C)
Class IIb
1. Patients with bioprosthetic valves may be considered
for annual echocardiograms after the first 5 years in
the absence of a change in clinical status. (Level of
Evidence: C)
Class III
1. Routine annual echocardiograms are not indicated in
the absence of a change in clinical status in patients
with mechanical heart valves or during the first 5 years
after valve replacement with a bioprosthetic valve.
(Level of Evidence: C)
9.3.1. First Outpatient Postoperative Visit
The first outpatient evaluation after valve surgery usually
occurs 3 to 4 weeks after hospital discharge. By this time, the
patient’s physical capabilities and expected improvement in
functional capacity can be assessed.
The workup on this visit should include an interval or
complete history and physical examination, ECG, chest
X-ray, 2D and Doppler echocardiography, complete blood
count, blood urea nitrogen/creatinine, electrolytes, lactate
dehydrogenase, and INR, if indicated. The main focus of the
examination is on signs that relate to function of the prosthesis or that might suggest the presence of infection or a
myocardial infarction, conduction, or valvular disorder. Severe perivalvular MR may be inaudible on physical examination, a fact to remember when one considers the possible
causes of functional deterioration in a patient. In patients who
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undergo surgery in the setting of acute valvular infection, the
first postoperative visit may occur at the end of a postoperative course of antibiotics. Surveillance blood cultures may be
indicated at this visit if 1 or more weeks have passed since
cessation of antibiotics to confirm bacteriologic cure.
Echocardiography is the most useful noninvasive test. It
provides information about prosthesis stenosis/regurgitation, valve area, assessment of other valve disease(s), pulmonary hypertension, atrial size, LV and RV hypertrophy,
LV and RV size and function, and pericardial effusion/
thickening. It is an essential component of the first postoperative visit because it allows an assessment of the effects and
results of surgery, as well as serving as a baseline for
comparison should complications or deterioration occur later.
Every prosthetic heart valve has an intrinsic degree of
obstruction857,989 –992; one reason for obtaining a baseline
Doppler echocardiogram early after valve replacement is so
that this intrinsic gradient can be measured and compared
with subsequent measurements if necessary. The gradient
varies among different types of prosthetic valves. Doppler
echocardiography also detects the prosthetic valve regurgitation that is normal for various types of mechanical valve.
Multiple other noninvasive tests (e.g., cardiac magnetic resonance) have emerged for the assessment of valvular and ventricular function, but these should be performed only in selected
patients for specific indications. Fluoroscopy can reveal abnormal rocking of a dehiscing prosthesis, limitation of the occluder
if the latter is opaque, and strut fracture of the convexoconcave
Björk-Shiley valve. Radionuclide angiography or cardiac magnetic resonance is useful to determine whether functional deterioration is the result of reduced ventricular function and is
performed if the same data cannot be obtained by echocardiography. Cardiac magnetic resonance is safe for all commercially
available prosthetic heart valves.
9.3.2. Follow-Up Visits in Patients Without Complications
Patients who have undergone valve replacement are not cured
but still have serious heart disease. They have exchanged
native valve disease for prosthetic valve disease and must be
followed with the same care as patients with native valve
disease.993 The clinical course of patients with prosthetic
heart valves is influenced by several factors,857 including LV
dysfunction, progression of other valve disease, pulmonary
hypertension, other cardiac diseases, complications of prosthetic heart valves, and clinical heart failure. The interval
between routine follow-up visits depends on the patient’s
needs. Anticoagulant regulation does not require visits to the
physician’s office but should be closely supervised by an
experienced healthcare professional.
The asymptomatic uncomplicated patient needs to be seen
only at 1-year intervals, at which time a complete history and
thorough physical examination should be performed. ECG
and chest X-ray examinations are not routinely indicated but
are valuable in individual patients. Additional tests that are
often performed include hemoglobin, hematocrit, and lactate
dehydrogenase. No further echocardiographic testing is required after the initial postoperative evaluation in patients
with mechanical valves who are stable and who have no
symptoms or clinical evidence of LV dysfunction, prosthetic
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valve dysfunction, or dysfunction of other heart valves, in
keeping with the ACC/AHA/ASE 2003 Guidelines for the
Clinical Application of Echocardiography.2 Once regurgitation is detected, close follow-up with 2D and Doppler
echocardiography every 3 to 6 months is indicated. Echocardiography is indicated in any patient with a prosthetic heart
valve whenever there is evidence of a new murmur or change
in clinical status, when there are questions about prosthetic
valve integrity and function, and when there are concerns
about ventricular function.
9.3.3. Follow-Up Visits in Patients With Complications
Class I
1. Patients with LV systolic dysfunction after valve surgery should receive standard medical therapy for
systolic heart failure. This therapy should be continued
even if there is improvement of LV dysfunction. (Level
of Evidence: B)
LV dysfunction and clinical heart failure after valve replacement may be the result of
• preoperative LV dysfunction that persists or improves only
partially
• perioperative myocardial damage
• other valve disease that has progressed
• complications of prosthetic heart valves
• associated heart disease such as CAD and systemic
hypertension.
Any patient with a prosthetic heart valve who does not improve
after surgery or who later shows deterioration of functional
capacity should undergo appropriate testing, including 2D and
Doppler echocardiography and, if necessary, transesophageal
echocardiography and cardiac catheterization with angiography
to determine the cause. Patients with postoperative LV systolic
dysfunction, even if asymptomatic, should receive standard
medical therapy for systolic heart failure, and this therapy should
be continued indefinitely even if there is improvement in systolic
function and/or symptoms. All patients should also receive
primary and secondary prevention measures to reduce the risk of
future cardiovascular events.
9.4. Reoperation to Replace a Prosthetic Valve
Reoperation to replace a prosthetic heart valve is a serious
clinical event. It is usually required for moderate to severe
prosthetic dysfunction (structural and nonstructural), dehiscence, and prosthetic endocarditis. Reoperation may also be
needed for recurrent thromboembolism, severe intravascular
hemolysis, severe recurrent bleeding from anticoagulant therapy, and thrombosed prosthetic valves In a patient with a
small aortic annulus, valve prosthesis-patient mismatch may
occur after AVR,856,989 –992,994,995 especially if a stented bioprosthesis is used. If a patient with AS does not improve
clinically after AVR, prosthetic valve function should be
evaluated. In selected situations, repeat AVR to replace a
malfunctioning prosthesis may be necessary.
The patient who is in stable condition without prosthetic
valve endocarditis under many circumstances undergoes reoperation with only slightly greater risk than that accompa-
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nying the initial surgery. For the patient with catastrophic
prosthetic valvular dysfunction, surgery is clearly indicated
and urgent. The patient without endocarditis or severe prosthetic valve dysfunction requires careful hemodynamic evaluation, and the decision about reoperation should then be
based on hemodynamic abnormalities, symptoms, ventricular
function, and current knowledge of the natural history of the
particular prosthesis.
10. Evaluation and Treatment of Coronary
Artery Disease in Patients with Valvular
Heart Disease
Many patients with valvular heart disease have concomitant
CAD, but there are only limited data regarding the optimal
strategies for diagnosis and treatment of CAD in such
patients. Thus, management decisions are usually developed
by blending information from the randomized studies of
treatment of CAD and the smaller published series of patients
undergoing surgical treatment of valvular heart disease.
10.1. Probability of Coronary Artery Disease in
Patients With Valvular Heart Disease
The probability of developing CAD in the general population996 and the prevalence of CAD in patients who come to
medical attention997 can be estimated on the basis of age, sex,
and clinical risk factors. The prevalence of CAD in patients
with valvular heart disease is determined by these same
variables.998 Risk factors for coronary atherosclerosis in
patients with valvular disease should be approached with the
prevention and risk reduction strategies that have been
recommended for the general population.999
Ischemic symptoms are important markers of CAD in the
general population. Thus, the prevalence of CAD (average)
has been estimated at 90% in middle-aged men with typical
angina AS, 50% in those with atypical angina, 16% in those
with nonanginal chest pain, and 4% in asymptomatic subjects.997 On the basis of data from the Framingham Study, the
rate of CAD increases with age, and in asymptomatic individuals who are low risk, it ranges from 1% to 6%. In those
aged less than 45 years, the risk is 1% to 2%.1000 In contrast,
ischemic symptoms in patients with valvular heart disease
may have multiple causes, such as LV chamber enlargement,
increased wall stress or wall thickening with subendocardial
ischemia,1001 and RV hypertrophy.1002 Angina is thus a less
specific indicator of CAD in patients with valvular heart
disease than in the general population.
Among patients with severe AS, angina is a common
symptom in young patients with normal coronary arteries and
congenital or rheumatic AS. On the other hand, CAD is a
common finding in older symptomatic men with AS. Among
patients with AS, the prevalence of CAD is 40% to 50% in
those with typical angina, an average 25% in those with
atypical chest pain, and an average 20% in those without
chest pain.1003–1010 Even in patients less than 40 years old with
no chest pain and no coronary risk factors, the prevalence of
CAD is 0% to 5%.998,1005,1011 In elderly patients (greater than
70 years old), angina is a strong determinant of CAD
(sensitivity 78%, specificity 82%).1012 Calcification of the
aortic valve is also associated with a high presence of CAD
(90%).1013 In general, because angina is a poor marker of
CAD in patients with AS, coronary angiography is recommended in symptomatic patients before AVR in men older
than 35 years; premenopausal women older than 35 years
with coronary risk factors, as well as asymptomatic men older
than 45 years; women older than 55 years; and those with 2
or more coronary risk factors.
CAD is less prevalent in patients with AR than in those
with AS,1003–1010,1014 –1020 which is related in part to the
younger age of patients with AR. The prevalence of CAD in
patients with MS (an average of 20%) is lower than in
patients with aortic valve disease,1015,1017,1018,1021,1022 an observation explained principally on the basis of differences in
age and gender. Nonetheless, because of the impact of
untreated CAD on perioperative and long-term postoperative
survival, preoperative identification of CAD is of great
importance in patients with AR or MS and those with AS.
Thus, in symptomatic patients and/or those with LV dysfunction, preoperative coronary angiography is recommended in
men aged greater than 35 years, premenopausal women aged
greater than 35 years with coronary risk factors, and postmenopausal women.
The relation between MR and CAD is unique in that CAD
is frequently the cause of this valve lesion. The management
of these patients is discussed in Section 3.6.5. Neither angina
nor heart failure symptoms are reliable markers of CAD in
these patients. In patients undergoing catheterization to evaluate the cause and severity of MR, CAD is present in an
average of 33%.1023,1024 In patients undergoing catheterization for acute ischemic syndromes, an average of 20% have
associated MR.(1025 Those with chronic CAD and MR
usually have lower LV ejection fractions and more extensive
CAD than those without MR.1023,1026 However, CAD is
infrequent in patients with degenerative MV disease undergoing surgery. In a large series, only 1.3% of such patients
had CAD, and they only had single-vessel disease. Thus,
routine coronary angiography is not indicated in patients
undergoing MV surgery for MR due to MV degeneration in
the absence of symptoms and without risk factors when they
are less than 45 years of age.1027
10.2. Diagnosis of Coronary Artery Disease
Class I
1. Coronary angiography is indicated before valve surgery (including infective endocarditis) or mitral balloon commissurotomy in patients with chest pain,
other objective evidence of ischemia, decreased LV
systolic function, history of CAD, or coronary risk
factors (including age). Patients undergoing mitral
balloon valvotomy need not undergo coronary angiography solely on the basis of coronary risk factors.
(Level of Evidence: C)
2. Coronary angiography is indicated in patients with
apparently mild to moderate valvular heart disease but
with progressive angina (Canadian Heart Association
functional Class II or greater), objective evidence of
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e631
ischemia, decreased LV systolic function, or overt
congestive heart failure. (Level of Evidence: C)
3. Coronary angiography should be performed before valve
surgery in men aged 35 years or older, premenopausal
women aged 35 years or older who have coronary risk
factors, and postmenopausal women. (Level of Evidence: C)
determined by noninvasive imaging and when patients have
known CAD, especially those with previous CABG (see Section
3.2.2.3).
Class IIa
Class I
1. Surgery without coronary angiography is reasonable
for patients having emergency valve surgery for acute
valve regurgitation, aortic root disease, or infective
endocarditis. (Level of Evidence: C)
1. Patients undergoing AVR with significant stenoses
(greater than or equal to 70% reduction in luminal
diameter) in major coronary arteries should be treated
with bypass grafting. (Level of Evidence: C)
Class IIb
Class IIa
1. Coronary angiography may be considered for patients
undergoing catheterization to confirm the severity of
valve lesions before valve surgery without pre-existing
evidence of CAD, multiple coronary risk factors, or
advanced age. (Level of Evidence: C)
1. In patients undergoing AVR and coronary bypass
grafting, use of the left internal thoracic artery is
reasonable for bypass of stenoses of the left anterior
descending coronary artery greater than or equal to
50% to 70%. (Level of Evidence: C)
2. For patients undergoing AVR with moderate stenosis
(50% to 70% reduction in luminal diameter), it is
reasonable to perform coronary bypass grafting in
major coronary arteries. (Level of Evidence: C)
Class III
1. Coronary angiography is not indicated in young patients
undergoing nonemergency valve surgery when no further
hemodynamic assessment by catheterization is deemed
necessary and there are no coronary risk factors, no
history of CAD, and no evidence of ischemia. (Level of
Evidence: C)
2. Patients should not undergo coronary angiography
before valve surgery if they are severely hemodynamically unstable. (Level of Evidence: C)
The resting ECG in patients with valvular heart disease
frequently shows ST-segment changes due to LV hypertrophy, LV dilatation, or bundle-branch block, which reduces
the accuracy of the ECG at rest and during exercise for the
diagnosis of concomitant CAD.
Similarly, resting or exercise-induced regional wall-motion
abnormalities are nonspecific markers for CAD in patients
with underlying valvular heart disease who have LV hypertrophy and/or chamber dilatation,1028 –1030 as are myocardial
perfusion abnormalities induced by exercise or pharmacological stress.1029,1031–1034 Limited data are available on the use of
myocardial perfusion imaging with thallium-201 or
technetium-99m perfusion agents in patients with severe
valvular disease. Although some studies of perfusion imaging
in AS have demonstrated a sensitivity of 87% and a specificity of 77%, the presence of CAD is missed in 13% of
patients with CAD.1035 Given the importance of determining
the presence of CAD, coronary angiography remains the most
appropriate method for the definitive diagnosis of CAD.1004
Noninvasive imaging is useful when CAD is suspected in
patients with mild valve stenosis or regurgitation and normal
LV cavity size and wall thickness.
In patients undergoing emergency valve surgery for acute AR,
aortic dissection, or endocarditis with hemodynamic instability,
cardiac catheterization, aortography, and coronary angiography
are rarely required, are associated with increased risk, and might
delay urgent surgery unnecessarily.221,224 –227 Angiography
should be considered only when the valve diagnosis cannot be
10.3. Treatment of Coronary Artery Disease at the
Time of Aortic Valve Replacement
As noted previously, more than 33% of patients with AS
who are undergoing AVR have concomitant CAD. More
than 50% of patients older than 70 years have CAD.
Several studies have reported the outcomes of patients
undergoing combined CABG and AVR. Although combined myocardial revascularization and AVR increases
cross-clamp time1036 and has the potential to increase
perioperative myocardial infarction and early postoperative mortality compared with patients without CAD undergoing isolated AVR,1037–1040 in several series, combined
CABG has had little or no adverse effect on operative
mortality.1041–1047 Moreover, combined CABG and AVR reduces the rates of perioperative myocardial infarction, operative
mortality, and late mortality and morbidity compared with
patients with significant CAD who do not undergo revascularization at the time of AVR.1045,1046,1048,1049 In addition to severity
of CAD, the multivariate factors for late postoperative mortality
include severity of AS, severity of LV dysfunction, age greater
than 70 years (especially in women), and presence of NYHA
functional class IV symptoms.1046,1050,1051 Incomplete revascularization is associated with greater postoperative systolic dysfunction1052,1053 and reduced survival rates1054 after surgery
compared with patients who receive complete revascularization.
For more than a decade, improved myocardial preservation
techniques have been associated with reduced overall operative
mortality,1055 and it has become standard practice to bypass all
significant coronary artery stenoses when possible in patients
undergoing AVR. The committee recommends this approach.
10.4. Aortic Valve Replacement in Patients
Undergoing Coronary Artery Bypass Surgery
Class I
1. AVR is indicated in patients undergoing CABG who
have severe AS who meet the criteria for valve replacement (see Section 3.1.7). (Level of Evidence: C)
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Class IIa
1. AVR is reasonable in patients undergoing CABG who
have moderate AS (mean gradient 30 to 50 mm Hg or
Doppler velocity 3 to 4 m per second). (Level of Evidence: B)
Class IIb
1. AVR may be considered in patients undergoing CABG
who have mild AS (mean gradient less than 30 mm Hg or
Doppler velocity less than 3 m per second) when there is
evidence, such as moderate-severe valve calcification, that
progression may be rapid. (Level of Evidence: C)
Patients undergoing CABG who have severe AS should undergo
AVR at the time of revascularization. Decision making is less
clear in patients who have CAD that requires CABG when these
patients have mild to moderate AS. Controversy persists regarding the indications for “prophylactic” AVR at the time of CABG
in such patients. This decision should be made only after the
severity of AS is determined by Doppler echocardiography and
cardiac catheterization.
Confirmation by cardiac catheterization is especially important in patients with reduced stroke volumes, mixed valve
lesions, or intermediate mean aortic valve gradients (between
30 and 50 mm Hg) by Doppler echocardiography, because
many such patients may actually have severe AS (as discussed in Section 3.1.6). The more complex and controversial
issue is the decision to replace the aortic valve for only mild
AS at the time of CABG, because the degree of AS may
become more severe within a few years, necessitating a
second, more difficult AVR operation in a patient with patent
bypass grafts.
It is difficult to predict whether a given patient with
CAD and mild AS is likely to develop significant AS in the
years after CABG. As noted previously (see Section 3.1.3),
the natural history of mild AS is variable, with some
patients manifesting a relatively rapid progression of AS
with a decrease in valve area of up to 0.3 cm2 per year and
an increase in pressure gradient of up to 15 to 19 mm Hg
per year; however, the majority may show little or no
change.61,86 –95,107,1056 The average rate of reduction in
valve area is 0.12 cm2 per year61, but the rate of change in
an individual patient is difficult to predict.
Retrospective studies of patients who have come to AVR
after previous CABG have been reported in which the mean
time to reoperation was 5 to 8 years.1057–1062 The aortic valve
gradient at the primary operation was small, less than 20 mm
Hg, but the mean gradient increased significantly to greater
than 50 mm Hg at the time of the second operation. These
reports represent selected patients in whom AS progressed to
the point that AVR was warranted. The number of patients in
these surgical series who had similar gradients at the time of
the primary operation but who did not have significant
progression of AS is unknown.
Although definitive data are not yet available, patients with
intermediate aortic valve gradients (mean gradient 30 to 50
mm Hg at catheterization or transvalvular velocity of 3 to 4 m
per second by Doppler echocardiography) who are undergoing CABG may warrant AVR at the time of revasculariza-
tion,181–185 whereas patients with gradients below 10 mm Hg
do not need valve replacement. The degree of mobility and
calcification are also important factors predicting more rapid
progression of aortic disease and should be taken into
consideration, particularly in those with gradients between 10
and 25 mm Hg.98,181,185–187,1063–1066 Because of the lack of
data, controversy exists regarding AVR at the time of CABG,
and the strength of these recommendations is reduced.
10.5. Management of Concomitant Mitral Valve
Disease and Coronary Artery Disease
Most patients with both MV disease and CAD have ischemic
MR, as discussed in Sections 3.6.5 and 7.3.1.3. In patients
with 1 to 2⫹ MR, ischemic symptoms usually dictate the
need for revascularization. Patients with more severe ischemic MR usually have significant LV dysfunction, and the
decision to perform revascularization and MV repair is based
on symptoms, severity of CAD, LV dysfunction, and inducible myocardial ischemia.
In patients with MV disease due to diseases other than
ischemia, significantly obstructed coronary arteries identified
at preoperative cardiac catheterization are generally revascularized at the time of MV surgery. There are no data to
indicate the wisdom of this general policy, but because
revascularization usually adds little morbidity or mortality to
the operation, the additional revascularization surgery is
usually recommended.
Staff – 2006 Guideline
American College of Cardiology Foundation
Thomas E. Arend, Jr., Esq., Interim Chief Staff Officer
Kristen N. Fobbs, Specialist, Practice Guidelines
Mark D. Stewart, MPH, Associate Director, EvidenceBased Medicine
Erin A. Barrett, Specialist, Clinical Policy and Documents
Kristina Petrie, MS, Associate Director, Practice Guidelines
Peg Christiansen, Librarian
American Heart Association
M. Cass Wheeler, Chief Executive Officer
Rose Marie Robertson, MD, FACC, FAHA, Chief
Science Officer
Kathryn A. Taubert, PhD, FAHA, Senior Scientist
Staff – 2008 Focused Update Incorporation
American College of Cardiology Foundation
John C. Lewin, MD, Chief Executive Officer
Charlene May, Senior Director, Science and Clinical Policy
Kennedy Elliott, Project Manager, Practice Guidelines
Sue Keller, BSN, MPH, Senior Specialist, EvidenceBased Medicine
Lisa Bradfield, Associate Director, Practice Guidelines
American Heart Association
Gayle R. Whitman, RN, PhD, FAAN, FAHA, Vice
President, Office of Science Operations
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1033. Rask LP, Karp KH, Eriksson NP, Mooe T. Dipyridamole thallium-201
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1035. Van TA. The value of myocardial perfusion imaging for diagnosing
coronary artery disease in patients with aortic valve stenosis. Adv
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valve replacement and myocardial revascularization: factors influencing early and late results. Scand J Thorac Cardiovasc Surg 1984;18:
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1037. Donzeau-Gouge P, Blondeau P, Enriquez O, et al. Calcified aortic
stenosis and coronary disease: apropos of 115 surgically-treated cases
[in French]. Arch Mal Coeur Vaiss 1984;77:856 – 64.
1038. Craver JM, Weintraub WS, Jones EL, Guyton RA, Hatcher CR Jr.
Predictors of mortality, complications, and length of stay in aortic
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1039. Stahle E, Bergstrom R, Nystrom SO, Hansson HE. Early results of
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1040. Aranki SF, Rizzo RJ, Couper GS, et al. Aortic valve replacement in the
elderly: effect of gender and coronary artery disease on operative
mortality. Circulation 1993;88:II17–23.
1041. Loop FD, Phillips DF, Roy M, Taylor PC, Groves LK, Effler DB.
Aortic valve replacement combined with myocardial revascularization:
late clinical results and survival of surgically-treated aortic valve
patients with and without coronary artery disease. Circulation 1977;
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valve replacement and aorta-coronary bypass surgery: results with
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1043. Nunley DL, Grunkemeier GL, Starr A. Aortic valve replacement with
coronary bypass grafting: significant determinants of ten-year survival.
J Thorac Cardiovasc Surg 1983;85:705–11.
1044. Kay PH, Nunley D, Grunkemeier GL, Garcia C, McKinley CL, Starr
A. Ten-year survival following aortic valve replacement: a multivariate
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1986;27:494 –9.
1045. Mullany CJ, Elveback LR, Frye RL, et al. Coronary artery disease and
its management: influence on survival in patients undergoing aortic
valve replacement. J Am Coll Cardiol 1987;10:66 –72.
1046. Czar LSC, Gray RJ, Stewart ME, De Robertis M, Chaux A, Matloff
JM. Reduction in sudden late death by concomitant revascularization
with aortic valve replacement. J Thorac Cardiovasc Surg 1988;95:390 –
400.
1047. Lytle BW, Cosgrove DM, Goormastic M, Loop FD. Aortic valve
replacement and coronary bypass grafting for patients with aortic
stenosis and coronary artery disease: early and late results. Eur Heart J
1988;9 Suppl E:143–7.
1048. Lund O, Nielsen TT, Pilegaard HK, Magnussen K, Knudsen MA. The
influence of coronary artery disease and bypass grafting on early and
late survival after valve replacement for aortic stenosis. J Thorac
Cardiovasc Surg 1990;100:327–37.
1049. Iung B, Drissi MF, Michel PL, et al. Prognosis of valve replacement for
aortic stenosis with or without coexisting coronary heart disease: a
comparative study. J Heart Valve Dis 1993;2:430 –9.
1050. Lytle BW, Cosgrove DM, Loop FD, et al. Replacement of aortic valve
combined with myocardial revascularization: determinants of early and
late risk for 500 patients, 1967–1981. Circulation 1983;68:1149 – 62.
1051. Magovern JA, Pennock JL, Campbell DB, et al. Aortic valve replacement and combined aortic valve replacement and coronary artery
bypass grafting: predicting high risk groups. J Am Coll Cardiol
1987;9:38 – 43.
1052. Schaff HV, Bixler TJ, Flaherty JT, et al. Identification of persistent
myocardial ischemia in patients developing left ventricular dysfunction
following aortic valve replacement. Surgery 1979;86:70 –7.
1053. Hwang MH, Hammermeister KE, Oprian C, et al. Preoperative
identification of patients likely to have left ventricular dysfunction after
aortic valve replacement. Participants in the Veterans Administration
Cooperative Study on Valvular Heart Disease. Circulation 1989;80:
I65–76.
1054. Roberts DL, DeWeese JA, Mahoney EB, Yu PN. Long-term survival
following aortic valve replacement. Am Heart J 1976;91:311–7.
1055. Galvin I, Mosieri J, Paneth M, Gibson D. An analysis of isolated aortic
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age. J Cardiovasc Surg (Torino) 1988;29:577– 81.
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1056. Cha SD, Naeem SM, Maranhao V, Gooch AS. Sequential study of left
ventricular function in aortic valvular stenosis. Cathet Cardiovasc
Diagn 1982;8:145–54.
1057. Collins JJ Jr, Aranki SF. Management of mild aortic stenosis during
coronary artery bypass graft surgery. J Card Surg 1994;9:145–7.
1058. Fiore AC, Swartz MT, Naunheim KS, et al. Management of asymptomatic mild aortic stenosis during coronary artery operations. Ann
Thorac Surg 1996;61:1693–7.
1059. Hoff SJ, Merrill WH, Stewart JR, Bender HW Jr. Safety of remote
aortic valve replacement after prior coronary artery bypass grafting.
Ann Thorac Surg 1996;61:1689 –91.
1060. Leprince P, Tsezana R, Dorent R, et al. Reoperation for aortic valve
replacement after myocardial revascularization. Arch Mal Coeur Vaiss
1996;89:335–9.
1061. Odell JA, Mullany CJ, Schaff HV, Orszulak TA, Daly RC, Morris JJ.
Aortic valve replacement after previous coronary artery bypass grafting. Ann Thorac Surg 1996;62:1424 –30.
1062. Phillips BJ, Karavas AN, Aranki SF, et al. Management of mild aortic
stenosis during coronary artery bypass surgery: an update, 1992–2001.
J Card Surg 2003;18:507–11.
1063. Eitz T, Kleikamp G, Minami K, Gleichmann U, Korfer R. Aortic valve
surgery following previous coronary artery bypass grafting: impact of
calcification and leaflet movement. Int J Cardiol 1998;64:125–30.
1064. Hochrein J, Lucke JC, Harrison JK, et al. Mortality and need for
reoperation in patients with mild-to-moderate asymptomatic aortic
valve disease undergoing coronary artery bypass graft alone. Am
Heart J 1999;138:791–7.
1065. Hilton TC. Aortic valve replacement for patients with mild to moderate
aortic stenosis undergoing coronary artery bypass surgery. Clin Cardiol
2000;23:141–7.
1066. Eitz T, Kleikamp G, Minami K, Korfer R. The prognostic value of
calcification and impaired valve motion in combined aortic stenosis
and coronary artery disease. J Heart Valve Dis 2002;11:713– 8.
1067. ACC/AHA Task Force on Practice Guidelines. Manual for ACC/AHA
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ACC/AHA Task Force on Practice Guidelines. Available at:
http://www.acc.org/qualityandscience/clinical/manual/pdfs/
methodology.pdf and http://circ.ahajournals.org/manual/. Accessed
June 2007.
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guidelines for the management of patients with valvular heart disease:
a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (writing Committee to
Revise the 1998 guidelines for the management of patients with
valvular heart disease) developed in collaboration with the Society of
Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic
Surgeons. J Am Coll Cardiol 2006;48:e1–148.
1069. Nishimura RA, Carabello BA, Faxon DP, et al. ACC/AHA 2008
guideline update on valvular heart disease: focused update on infective
endocarditis prophylaxis. J Am Coll Cardiol 2008;52:676 – 85.
1070. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective
endocarditis: guidelines from the American Heart Association: a
guideline from the American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology,
Council on Cardiovascular Surgery and Anesthesia, and the Quality of
Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007;116:1736 –54.
1071. Baddour LM, Bettmann MA, Bolger AF, et al. Nonvalvular cardiovascular device-related infections. Circulation 2003;108:2015–31.
1072. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008
guidelines for the management of adults with congenital heart disease:
a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to
Develop Guidelines for the Management of Adults With Congenital
Heart Disease). J Am Coll Cardiol 2008. In press.
1073. Horstkotte D, Follath F, Gutschik E, et al. Guidelines on prevention,
diagnosis and treatment of infective endocarditis executive summary;
the task force on infective endocarditis of the European society of
cardiology. Eur Heart J 2004;25:267–76.
1074. Gould FK, Elliott TS, Foweraker J, et al. Guidelines for the prevention
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Antimicrobial Chemotherapy J Antimicrob Chemother 2006;57:1035–
42.
KEY WORDS: ACC/AHA practice guideline 䡲 valvular heart diseaseheart
valves 䡲 cardiac murmur 䡲 valve lesion 䡲 thoracic surgery.
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Appendix 1. Author Relationships With Industry—ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart
Disease
Committee Member
Research Grant
Stock Ownership/
Patents
Speakers’ Bureau
Board of
Directors
Consultant/Advisory Board
Robert O. Bonow, MD
None
None
None
None
Had a prior relationship with Wyeth
Pharmaceuticals regarding
anorectic drugs
Blase A. Carabello, MD
None
None
None
None
None
Kanu Chatterjee, MD
None
●
Astra-Zeneca
Bristol-Myers
Squibb
● MSD
● Scios
None
None
●
None
●
Antonio C. de Leon, Jr.,
MD
None
None
David P. Faxon, MD
None
●
●
Aventis-Sanofi
Bristol-Myers
Squibb
●
●
Medical Technologies
International
CV Therapeutics
Yamanouchi
None
None
None
●
●
Boston Scientific
Johnson & Johnson
Michael D. Freed, MD
None
None
None
None
None
William H. Gaasch, MD
None
None
None
None
None
Bruce W. Lytle, MD
None
None
●
None
●
Rick A. Nishimura, MD
None
None
None
None
None
Patrick O’Gara, MD
None
None
None
None
None
Robert O’Rourke, MD
●
Merck
Pfizer
None
None
None
None
St. Jude
Medical
None
●
None
None
●
Johnson & Johnson
Patent pending on
use of ACE inhibitors
Shares purchased on open
market. No options.
Catherine M. Otto, MD
●
Pravin M. Shah, MD
None
None
None
None
●
Jack Shanewise, MD
None
None
None
None
None
FenPhen litigation
This table represents the relationships of committee members with industry that were reported orally at the initial writing committee meeting and updated in
conjunction with all meetings and conference calls of the writing committee during the document development process. It does not necessarily reflect relationships
with industry at the time of publication.
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e657
Appendix 2. Peer Reviewer Relationships With Industry—ACC/AHA 2006 Guidelines for the Management of Patients With Valvular
Heart Disease
Peer Reviewer*†
Representation
Research Grant
Speakers’ Bureau/
Honoraria
Stock
Ownership
Consultant/
Advisory Board
Dr. Mazen Abu-Fadel
●
Content Reviewer—ACCF
Cardiac Catheterization and
Intervention Committee
None
None
None
None
Dr. Lishan Akolg
●
Organizational Reviewer—
Society of Thoracic Surgeons
None
None
None
●
Content Reviewer—Individual
None
Dr. Joseph Alpert
●
Guidant
J&
J Cardiovations
● Medical CV
● Medtronic
● Myocor
● St. Jude Medical
●
Exeter, Inc
None
EK Guard
Novartis
● Sanofi-Aventis
●
●
Dr. Jeffrey Anderson
●
Content Reviewer—Individual
None
●
Bristol-Myers
Squibb/Sanofi
● diaDexus
● Merck
None
Merck
Dr. Larry Baddour
●
Content Reviewer—AHA
Rheumatic Fever, Endocarditis,
and Kawasaki Disease
Committee
None
None
None
None
Dr. Simon Body
●
Organizational Reviewer—
Society of Cardiovascular
Anesthesiologists
●
None
None
None
Dr. Ann Bolger
●
Official Reviewer (cardiology)—
AHA Rheumatic Fever,
Endocarditis, and Kawasaki
Disease Committee
None
None
None
None
Dr. Charles Bridges
●
Organizational Reviewer—
Society of Thoracic Surgeons
None
None
None
None
Dr. Jay Brophy
●
Official Reviewer—Board of
Governors
None
None
None
None
Dr. Matthew Budoff
●
Content Reviewer—AHA
Cardiovascular Imaging and
Intervention Committee
None
●
None
None
Dr. Melvin Chietlin
●
Content Reviewer—Individual
Review
None
None
None
None
Dr. John Child
●
Content Reviewer—ACC/AHA
Management of Adults With
Congenital Heart Disease
None
None
None
None
Dr. Michael Crawford
●
Content Reviewer—Individual
None
None
None
None
Dr. Ted Feldman
●
Organizational Reviewer—
Society for Cardiovascular
Angiography and Interventions
●
Abbott
Atritech
● Bristol-Myers
Squibb
● Cardiac
Dimensions
● Cordis
● Evalve
None
None
●
Official Reviewer—Board of
Trustees Review
None
None
None
None
Dr. Linda Gillam
●
Bayer
Diagnostics
General Electric
●
Bristol-Myers
Squibb
● Cardiac
Dimensions
● Cordis
● Guidant
● Myocor
(Continued)
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Peer Reviewer*†
Dr. Ami Iskandrian
Speakers’ Bureau/
Honoraria
Stock
Ownership
Astellas Pharma
Bristol-Myers
Squibb
● CV Therapeutics
● GE Healthcare
● Molecular Insight
None
None
Representation
Content Reviewer—ACCF
Cardiovascular Imaging
Committee
● Content Reviewer—AHA
Cardiovascular Imaging and
Intervention Committee
● Content Reviewer—AHA Cardiac
Imaging Committee
●
Research Grant
●
●
Consultant/
Advisory Board
Acusphere
(Blinded Reader)
● CV Therapeutics
● International
Atomic Energy
(IAEA)
●
Dr. Donald Larsen
●
Content Reviewer—AHA
Cerebrovascular Imaging and
Intervention Committee
None
●
Dr. Peter Lockhart
●
Content Reviewer—AHA
Rheumatic Fever, Endocarditis,
and Kawasaki Disease
Committee
None
None
None
None
Dr. Joseph Mathew
●
Organizational Reviewer—
Society of Cardiovascular
Anesthesiologists
None
None
None
None
Dr. Debabrata Mukherjee
●
Content Reviewer—ACCF
Cardiac Catheterization and
Intervention Committee
None
None
None
None
Dr. Robert Robbins
●
Official Reviewer (surgery)—
AHA
None
None
None
None
Dr. Carlos Ruiz
●
Content Reviewer—ACCF
Cardiac Catheterization and
Intervention Committee
None
None
None
None
Dr. Richard Shemin
●
Content Reviewer—ACCF
Cardiovascular Surgery
Committee
● Organizational Reviewer—
Society of Thoracic Surgeons
None
None
None
●
Microvention
●
Gardant
●
Microtherapeutics
3F Therapeutics
Edwards Life
Sciences
● St. Jude Medical
●
Dr. Stanton Shernan
●
Organizational Reviewer—
Society of Cardiovascular
Anesthesiologists
None
Dr. Thoralf Sundt
●
Content Reviewer—ACCF
Cardiac Catheterization and
Intervention Committee
●
Dr. Kathryn Taubert
●
Content Reviewer—AHA
Rheumatic Fever, Endocarditis,
and Kawasaki Disease
Committee
Dr. Zoltan Turi
●
Dr. Roberta Williams
Dr. William Zoghbi
None
None
None
None
None
None
None
None
None
None
Organizational Reviewer—
Society for Cardiovascular
Angiography and Interventions
None
None
None
None
●
Content Reviewer—ACC/AHA
Management of Adults With
Congenital Heart Disease
None
None
None
None
●
Content Reviewer—Individual
None
None
None
None
CarboMedics
This table represents the relationships of peer reviewers with industry that were disclosed at the time of peer review of this guideline. It does not necessarily reflect
relationships with industry at the time of publication.
*Participation in the peer review process does not imply endorsement of the document.
†Names are listed in alphabetical order within category of review.
ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; and AHA, American Heart Association.
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e659
Appendix 3. Abbreviation List
ACC ⫽ American College of Cardiology
INR ⫽ international normalized ratio
ACCF ⫽ American College of Cardiology Foundation
LMWH ⫽ low-molecular-weight heparin
ACE ⫽ angiotensin converting enzyme
LV ⫽ left ventricular
AHA ⫽ American Heart Association
MR ⫽ mitral regurgitation
aPTT ⫽ activated partial thromboplastin time
MS ⫽ mitral stenosis
AR ⫽ aortic regurgitation
MV ⫽ mitral valve
AS ⫽ aortic stenosis
MVP ⫽ mitral valve prolapse
AVR ⫽ aortic valve replacement
NYHA ⫽ New York Heart Association
CAD ⫽ coronary artery disease
RV ⫽ right ventricular
CABG ⫽ coronary artery bypass surgery
STS ⫽ Society of Thoracic Surgeons
ECG ⫽ electrocardiogram
TR ⫽ tricuspid regurgitation
FDA ⫽ Food and Drug Administration
2D ⫽ two-dimensional
HIV ⫽ human immunodeficiency virus
UFH ⫽ unfractionated heparin
Appendix 4. Author Relationships With Industry—ACC/AHA 2008 Guideline Update on Valvular Heart Disease: Focused Update on
Infective Endocarditis Writing Committee
Committee Member
Consultant
Speakers’ Bureau/
Honoraria
Ownership/
Partnership/
Principal
Research
Institutional,
Organizational, or
Other Financial
Benefit
Expert Witness
Dr. Rick A. Nishimura
None
None
None
None
None
None
Dr. Blase A. Carabello
None
None
None
None
None
None
Dr. David P. Faxon
●
Boston Scientific
Bristol-Myers Squibb
● GlaxoSmithKline
● Johnson & Johnson
None
None
None
None
None
Dr. Michael D. Freed
None
None
None
None
None
None
Dr. Bruce W. Lytle
None
None
None
None
None
None
Dr. Patrick T. O’Gara
None
None
None
None
None
None
Dr. Robert A. O’Rourke
None
None
None
None
None
None
Dr. Pravin M. Shah
●
None
None
None
None
None
●
Edwards LifeSciences
This table represents the relationships of committee members with industry that were reported orally at the initial writing committee meeting and updated in
conjunction with all meetings and conference calls of the writing committee during the document development process. It does not necessarily reflect relationships
with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% or more of the
voting stock or share of the business entity, or ownership of $10 000 or more of the fair market value of the business entity; or if funds received by the person from
the business entity exceed 5% of the person’s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the
preceding definition. Relationships in this table are modest unless otherwise noted.
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Appendix 5. Peer Reviewer Relationships With Industry—ACC/AHA 2008 Guideline Update on Valvular Heart Disease: Focused Update
on Infective Endocarditis
Peer Reviewer*
Representation
Dr. Ann F. Bolger
● Official AHA
Reviewer
Dr. Paul L.
Douglass
●
Dr. Timothy J.
Gardner
● Official AHA
Reviewer
Dr. Chittur A.
Sivaram
●
Dr. David Aguilar
Consultant
Speakers’ Bureau/
Honoraria
Ownership/
Partnership/
Principal
Research
Institutional,
Organizational,
or Other
Financial Benefit
Expert
Witness
None
None
None
None
None
None
●
Aventis
Merck
● Novartis
●
Bayer Healthcare
Bristol-Myers
Squibb
● Pfizer
None
None
None
None
●
●
None
None
None
None
None
None
Official
Reviewer—ACCF
Board of
Governors
None
None
None
None
None
None
●
Content
Reviewer—AHA
Heart Failure &
Transplant
Committee
None
None
None
None
None
None
Dr. Larry M.
Baddour
●
Content
Reviewer—AHA
Rheumatic Fever,
Endocarditis, &
Kawasaki Disease
Committee
●
American
College of
Physicians
● Enturia
● UpToDate
None
None
None
None
None
Dr. Louis I. Bezold
●
Content
Reviewer—ACC
Congenital Heart
Disease &
Pediatric
Committee
None
None
None
None
None
None
Dr. Robert O.
Bonow
●
Content
Reviewer—2006
Writing Committee
Chair
None
None
None
None
None
None
Dr. A. Michael
Borkon
●
Content
Reviewer—ACC
Cardiovascular
Surgery Committee
None
None
None
None
None
None
Dr. Jeffrey A.
Feinstein
●
Content
Reviewer—ACC
Congenital Heart
Disease &
Pediatric
Committee
None
None
None
None
None
None
Dr. Gary S. Francis
●
Content
Reviewer—AHA
Heart Failure &
Transplant
Committee
●
Boehringer
Ingelheim
● Johnson &
Johnson
● NitroMed
● Novartis
● Otsuka
None
None
●
National
Institutes of
Health†
● Pfizer†
None
None
Official
Reviewer—ACCF
Board of Trustees
(Continued)
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Bonow et al
Peer Reviewer*
Representation
ACC/AHA VHD Guidelines: 2008 Focused Update Incorporated
e661
Institutional,
Organizational,
or Other
Financial Benefit
Expert
Witness
Consultant
Speakers’ Bureau/
Honoraria
Ownership/
Partnership/
Principal
Research
Dr. Wayne L.
Miller
●
Content
Reviewer—AHA
Heart Failure &
Transplant
Committee
None
None
None
None
None
None
Dr. Judith E.
Mitchell
●
Content
Reviewer—AHA
Heart Failure &
Transplant
Committee
●
Astellas
GlaxoSmithKline
● NitroMed
None
None
None
None
None
Dr. John B.
O’Connell
●
Content
Reviewer—AHA
Heart Failure &
Transplant
Committee
None
None
None
None
None
None
Dr. Geoffrey L.
Rosenthal
●
Content
Reviewer—ACC
Congenital Heart
Disease &
Pediatric
Committee
None
None
None
None
None
None
Dr. Anne Rowley
●
Content
Reviewer—AHA
Rheumatic Fever,
Endocarditis, &
Kawasaki Disease
Committee
None
None
None
None
None
None
Dr. Hartzell V.
Schaff
●
Content
Reviewer—ACC
Cardiovascular
Surgery Committee
None
None
None
●
AtriCure
Bolton Medical
● Jarvik Heart
● Medtronic
● Sorin Group/
Carbomedics
● St. Jude
● Thoratec
● W.L. Gore and
Associates
●
●
●
Dr. Kathryn A.
Taubert
●
Content
Reviewer—AHA
Rheumatic Fever,
Endocarditis, &
Kawasaki Disease
Committee
None
None
None
●
None
None
Sorin Group†
St. Jude†
None
None
This table represents the relationships with industry that were disclosed at the time of peer review. It does not necessarily reflect relationships with industry at
the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% or more of the voting stock or share
of the business entity, or ownership of $10 000 or more of the fair market value of the business entity; or if funds received by the person from the business entity
exceed 5% of the person’s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition.
Relationships in this table are modest unless otherwise noted.
*Names are listed in alphabetical order within each category of review.
†Significant (greater than $10 000) relationship.
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