Author + information
- Published online December 2, 2008.
- Carole A. Warnes, MD, FRCP, FACC, FAHA, Co-Chair, WRITING COMMITTEE MEMBER,
- Roberta G. Williams, MD, MACC, FAHA, Co-Chair, WRITING COMMITTEE MEMBER,
- Thomas M. Bashore, MD, FACC, WRITING COMMITTEE MEMBER,
- John S. Child, MD, FACC, FAHA, WRITING COMMITTEE MEMBER,
- Heidi M. Connolly, MD, FACC, WRITING COMMITTEE MEMBER,
- Joseph A. Dearani, MD, FACC, WRITING COMMITTEE MEMBER⁎,
- Pedro del Nido, MD, WRITING COMMITTEE MEMBER,
- James W. Fasules, MD, FACC, WRITING COMMITTEE MEMBER,
- Thomas P. Graham Jr, MD, FACC, WRITING COMMITTEE MEMBER†,
- Ziyad M. Hijazi, MBBS, MPH, FACC, FSCAI, WRITING COMMITTEE MEMBER‡,
- Sharon A. Hunt, MD, FACC, FAHA, WRITING COMMITTEE MEMBER,
- Mary Etta King, MD, FACC, FASE, WRITING COMMITTEE MEMBER§,
- Michael J. Landzberg, MD, FACC, WRITING COMMITTEE MEMBER,
- Pamela D. Miner, RN, MN, NP, WRITING COMMITTEE MEMBER,
- Martha J. Radford, MD, FACC, WRITING COMMITTEE MEMBER,
- Edward P. Walsh, MD, FACC, WRITING COMMITTEE MEMBER∥ and
- Gary D. Webb, MD, FACC, WRITING COMMITTEE MEMBER¶
- ACC/AHA Practice Guidelines
- congenital heart disease
- cardiac defects
- congenital heart surgery
- unoperated/repaired heart defects
- medical therapy
- cardiac catheterization
Task Force Members
Sidney C. Smith, Jr, MD, FACC, FAHA, Chair; Alice K. Jacobs, MD, FACC, FAHA, Vice-Chair; Cynthia D. Adams, RSN, PhD, FAHA#; Jeffrey L. Anderson, MD, FACC, FAHA#; Elliott M. Antman, MD, FACC, FAHA⁎⁎; Christopher E. Buller, MD, FACC; Mark A. Creager, MD, FACC, FAHA; Steven M. Ettinger, MD, FACC; Jonathan L. Halperin, MD, FACC, FAHA#; Sharon A. Hunt, 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; Barbara Riegel, DNSc, RN, FAHA#; Lynn G. Tarkington, RN; Clyde W. Yancy, MD, FACC, FAHA
Table of Contents
1.1. Methodology and Evidence Review.......e150
1.2. Organization of Committee and Relationships With Industry.......e151
1.3. Document Review and Approval.......e151
1.4. Epidemiology and Scope of the Problem.......e151
1.5. Recommendations for Delivery of Care and Ensuring Access.......e151
1.5.1. Recommendations for Access to Care.......e154
1.5.2. Recommendations for Psychosocial Issues.......e155
1.5.3. Transition of Care.......e156
1.5.4. Exercise and Athletics.......e157
1.5.7. Congenital Syndromes.......e158
1.5.8. Medical/Ethical/Legal Issues.......e158
1.6. Recommendations for Infective Endocarditis.......e159
1.7. Recommendations for Noncardiac Surgery.......e163
1.8. Recommendations for Pregnancy and Contraception.......e163
1.9. Recommendations for Arrhythmia Diagnosis and Management.......e164
1.9.1. Management of Tachyarrhythmias: Wolff-Parkinson-White Syndrome.......e165
1.9.2. Intra-Atrial Reentrant Tachycardia or Atrial Flutter.......e165
1.9.3. Atrial Fibrillation.......e166
1.9.4. Ventricular Tachycardia.......e166
1.10. Management of Bradycardias.......e167
1.10.1. Sinoatrial Node Dysfunction.......e167
1.10.2. Atrioventricular Block.......e168
1.11. Cyanotic Congenital Heart Disease.......e168
1.11.1. Recommendations for Hematologic Problems.......e168
22.214.171.124. Renal Function.......e169
126.96.36.199. Orthopedic and Rheumatologic Complications.......e169
188.8.131.52. Neurological Complications.......e169
184.108.40.206. Pulmonary Vascular Disease.......e169
1.12. Recommendations for General Health Issues for Cyanotic Patients.......e169
1.12.1. Hospitalization and Operation.......e169
1.12.2. Cardiac Reoperation and Preoperative Evaluation.......e169
1.13. Heart Failure in Adult Congenital Heart Disease.......e170
1.14. Recommendations for Heart and Heart/Lung Transplantation.......e172
2. Atrial Septal Defect.......e173
2.1.1. Associated Lesions.......e173
2.2. Clinical Course.......e173
2.2.1. Unrepaired Atrial Septal Defect.......e173
2.3. Recommendations for Evaluation of the Unoperated Patient.......e174
2.3.1. Clinical Examination.......e174
2.3.3. Chest X-Ray.......e174
2.3.5. Magnetic Resonance Imaging.......e174
2.3.6. Exercise Testing.......e175
2.4. Diagnostic Problems and Pitfalls.......e175
2.5. Management Strategies.......e175
2.5.1. Recommendations for Medical Therapy.......e175
2.5.2. Recommendations for Interventional and Surgical Therapy.......e175
2.5.3. Indications for Closure of Atrial Septal Defect.......e176
2.5.4. Catheter Intervention.......e176
2.5.5. Key Issues to Evaluate and Follow-Up.......e176
2.6. Recommendations for Postintervention Follow-Up.......e176
2.6.1. Endocarditis Prophylaxis.......e176
2.6.2. Recommendation for Reproduction.......e177
3. Ventricular Septal Defect.......e178
3.1.1. Associated Lesions.......e178
3.2. Clinical Course (Unrepaired).......e179
3.3. Clinical Features and Evaluation of the Unoperated Patient.......e179
3.3.1. Clinical Examination.......e179
3.3.3. Chest X-Ray.......e179
3.3.5. Magnetic Resonance Imaging/Computed Tomography.......e179
3.3.6. Recommendations for Cardiac Catheterization.......e180
3.4. Diagnostic Problems and Pitfalls.......e180
3.5. Management Strategies.......e180
3.5.1. Recommendation for Medical Therapy.......e180
3.5.2. Recommendations for Surgical Ventricular Septal Defect Closure.......e180
3.5.3. Recommendation for Interventional Catheterization.......e180
3.6. Key Issues to Evaluate and Follow-Up.......e181
3.6.1. Recommendations for Surgical and Catheter Intervention Follow-Up.......e181
3.6.2. Recommendation for Reproduction.......e181
4. Atrioventricular Septal Defect.......e181
4.2. Associated Lesions.......e181
4.3. Clinical Features and Evaluation.......e181
4.3.1. Clinical Examination.......e182
4.3.3. Chest X-Ray.......e182
4.3.5. Magnetic Resonance Imaging.......e182
4.3.6. Recommendation for Heart Catheterization.......e182
4.3.7. Exercise Testing.......e182
4.4. Management Strategies.......e182
4.4.1. Medical Therapy.......e182
4.4.2. Recommendations for Surgical Therapy.......e182
4.5. Key Issues to Evaluate and Follow-Up.......e183
4.5.1. Key Postoperative Issues.......e183
4.5.2. Evaluation and Follow-Up of the Repaired Patient.......e183
4.5.3. Electrophysiology Testing/Pacing Issues in Atrioventricular Septal Defects.......e183
4.5.4. Recommendations for Endocarditis Prophylaxis.......e183
4.6.1. Genetic Aspects.......e183
4.6.2. Recommendations for Pregnancy.......e183
5. Patent Ductus Arteriosus.......e184
5.1. Definition and Associated Lesions.......e184
5.2. Presentation and Clinical Course.......e184
5.3. Recommendations for Evaluation of the Unoperated Patient.......e184
5.3.1. Clinical Examination.......e184
5.3.4. Chest X-Ray.......e184
5.3.5. Cardiac Catheterization.......e184
5.3.6. Magnetic Resonance Imaging/Computed Tomography.......e184
5.4. Problems and Pitfalls.......e184
5.5. Management Strategies.......e185
5.5.1. Recommendations for Medical Therapy.......e185
5.5.2. Recommendations for Closure of Patent Ductus Arteriosus.......e185
5.5.3. Surgical/Interventional Therapy.......e185
5.6. Key Issues to Evaluate and Follow-Up.......e185
6. Left-Sided Heart Obstructive Lesions: Aortic Valve Disease, Subvalvular and Supravalvular Aortic Stenosis, Associated Disorders of the Ascending Aorta, and Coarctation.......e185
6.2. Associated Lesions.......e186
6.3. Clinical Course (Unrepaired).......e186
6.4. Recommendations for Evaluation of the Unoperated Patient.......e186
6.4.1. Clinical Examination.......e187
6.4.3. Chest X-Ray.......e187
6.4.5. Magnetic Resonance Imaging/Computed Tomography.......e187
6.4.6. Stress Testing.......e187
6.4.7. Cardiac Catheterization.......e187
6.5. Problems and Pitfalls.......e188
6.6. Management Strategies for Left Ventricular Outflow Tract Obstruction and Associated Lesions.......e188
6.6.1. Recommendations for Medical Therapy.......e188
6.6.2. Catheter and Surgical Intervention.......e188
220.127.116.11. Recommendations for Catheter Interventions for Adults With Valvular Aortic Stenosis .......e188
18.104.22.168. Recommendations for Aortic Valve Repair/Replacement and Aortic Root Replacement.......e189
6.7. Recommendations for Key Issues to Evaluate and Follow-Up.......e190
6.8. Isolated Subaortic Stenosis.......e190
6.8.2. Associated Lesions.......e191
6.8.3. Clinical Course With/Without Previous Intervention.......e191
6.8.4. Clinical Features and Evaluation.......e191
22.214.171.124. Clinical Examination.......e191
126.96.36.199. Chest X-Ray.......e191
6.8.5. Diagnostic Cardiac Catheterization.......e191
6.8.6. Problems and Pitfalls.......e191
6.8.7. Management Strategies.......e191
188.8.131.52. Medical Therapy.......e191
184.108.40.206. Recommendations for Surgical Intervention.......e191
6.8.8. Recommendations for Key Issues to Evaluate and Follow-Up.......e192
6.8.9. Special Issues.......e192
220.127.116.11. Exercise and Athletics.......e192
6.9. Supravalvular Aortic Stenosis.......e192
6.9.2. Associated Lesions.......e192
6.9.3. Clinical Course (Unrepaired).......e192
6.10. Recommendations for Evaluation of the Unoperated Patient.......e193
6.10.1. Clinical Examination.......e193
6.10.3. Chest X-Ray.......e193
6.10.5. Stress Testing.......e193
6.10.6. Myocardial Perfusion Imaging.......e193
6.10.7. Cardiac Catheterization.......e193
6.11. Management Strategies for Supravalvular Left Ventricular Outflow Tract.......e193
6.11.1. Recommendations for Interventional and Surgical Therapy.......e193
6.11.2. Recommendations for Key Issues to Evaluate and Follow-Up.......e194
6.11.3. Special Issues.......e194
6.11.4. Exercise and Athletics.......e194
6.11.5. Recommendations for Reproduction.......e194
6.12. Aortic Coarctation.......e194
6.12.2. Associated Lesions.......e194
6.12.3. Recommendations for Clinical Evaluation and Follow-Up.......e194
6.13. Clinical Features and Evaluation of Unrepaired Patients.......e195
6.13.2. Chest X-Ray.......e195
6.13.3. Echocardiography and Doppler.......e195
6.13.4. Stress Testing.......e195
6.13.5. Magnetic Resonance Imaging/Magnetic Resonance Angiography or Computed Tomography With 3-Dimensional Reconstruction.......e195
6.13.6. Catheterization Hemodynamics/Angiography.......e195
6.13.7. Problems and Pitfalls.......e195
6.14. Management Strategies for Coarctation of the Aorta.......e195
6.14.1. Medical Therapy.......e195
6.14.2. Recommendations for Interventional and Surgical Treatment of Coarctation of the Aorta in Adults.......e195
6.14.3. Recommendations for Key Issues to Evaluate and Follow-Up.......e196
6.14.4. Exercise and Athletics.......e196
6.14.6. Endocarditis Prophylaxis.......e197
7. Right Ventricular Outflow Tract Obstruction.......e197
7.2. Associated Lesions.......e197
7.3. Valvular Pulmonary Stenosis.......e198
7.4. Clinical Course.......e198
7.4.1. Unrepaired Patients.......e198
7.4.2. Noonan Syndrome Patients With Prior Repair.......e198
7.5. Recommendations for Evaluation of the Unoperated Patient.......e198
7.5.1. Clinical Examination.......e198
7.5.3. Chest X-Ray.......e198
7.5.5. Magnetic Resonance Imaging/Computed Tomography.......e199
7.5.6. Cardiac Catheterization.......e199
7.5.7. Relationship Between Peak Instantaneous Doppler Echocardiographic Pressure Gradients and Peak-to-Peak Cardiac Catheterization Gradients.......e199
7.6. Problems and Pitfalls.......e199
7.6.2. Chest Pain.......e199
7.6.3. Enlarging Right Ventricle.......e199
7.6.4. Pulmonary Arterial Hypertension.......e200
7.6.6. Systemic Venous Congestion.......e200
7.7. Management Strategies.......e200
7.7.1. Recommendations for Intervention in Patients With Valvular Pulmonary Stenosis.......e200
7.7.2. Percutaneous Balloon Pulmonary Valvotomy.......e200
7.7.3. Surgical Pulmonary Valvotomy or Valve Replacement.......e201
7.8. Recommendation for Clinical Evaluation and Follow-Up After Intervention.......e201
7.8.2. Endocarditis Prophylaxis.......e202
7.8.3. Exercise and Athletics.......e202
7.9. Right-Sided Heart Obstruction Due to Supravalvular, Branch, and Peripheral Pulmonary Artery Stenosis.......e202
7.9.1. Definition and Associated Lesions.......e202
7.9.2. Clinical Course.......e202
7.10. Clinical Features and Evaluation of the Unrepaired Patient.......e202
7.10.2. Chest X-Ray.......e203
7.10.4. Magnetic Resonance Imaging/Computed Tomography.......e203
7.10.5. Cardiac Catheterization.......e203
7.11. Recommendations for Evaluation of Patients With Supravalvular, Branch, and Peripheral Pulmonary Stenosis.......e203
7.11.1. Problems and Pitfalls.......e203
7.11.2. Management Strategies.......e203
18.104.22.168. Medical Therapy.......e203
7.12. Recommendations for Interventional Therapy in the Management of Branch and Peripheral Pulmonary Stenosis.......e203
7.12.1. Recommendations for Evaluation and Follow-Up.......e204
7.13. Right-Sided Heart Obstruction Due to Stenotic Right Ventricular–Pulmonary Artery Conduits or Bioprosthetic Valves.......e204
7.13.1. Definition and Associated Lesions.......e204
7.13.2. Recommendation for Evaluation and Follow-Up After Right Ventricular–Pulmonary Artery Conduit or Prosthetic Valve.......e204
7.13.3. Clinical Examination.......e204
7.13.5. Chest X-Ray.......e204
7.13.7. Magnetic Resonance Imaging/Computed Tomography.......e204
7.13.8. Cardiac Catheterization.......e204
7.14. Recommendations for Reintervention in Patients With Right Ventricular–Pulmonary Artery Conduit or Bioprosthetic Pulmonary Valve Stenosis.......e204
7.14.1. Medical Therapy.......e205
7.14.2. Interventional Catheterization.......e205
7.14.3. Surgical Intervention.......e205
7.14.4. Key Issues to Evaluate and Follow-Up.......e205
7.15. Double-Chambered Right Ventricle.......e205
7.15.1. Definition and Associated Lesions.......e205
7.15.2. Clinical Features and Evaluation of the Unoperated Patient.......e205
7.15.3. Clinical Examination.......e206
7.15.5. Echocardiography-Doppler Imaging.......e206
7.15.6. Magnetic Resonance Imaging.......e206
7.15.7. Cardiac Catheterization.......e206
7.16. Problems and Pitfalls.......e206
7.16.1. Multiple Levels of Right Ventricular Outflow Tract Obstruction.......e206
7.17. Management Strategies.......e206
7.17.1. Recommendations for Intervention in Patients With Double-Chambered Right Ventricle.......e206
7.18. Key Issues to Evaluate and Follow-Up.......e206
8. Coronary Artery Abnormalities.......e206
8.1. Definition and Associated Lesions.......e206
8.1.1. General Recommendations for Evaluation and Surgical Intervention.......e206
8.2. Recommendations for Coronary Anomalies Associated With Supravalvular Aortic Stenosis.......e207
8.2.1. Clinical Course (Unrepaired) .......e207
8.2.2. Clinical Features.......e207
8.3. Recommendation for Coronary Anomalies Associated With Tetralogy of Fallot.......e207
8.3.1. Preintervention Evaluation.......e207
8.3.2. Surgical and Catheterization-Based Interventions.......e207
8.4. Recommendation for Coronary Anomalies Associated With Dextro-Transposition of the Great Arteries After Arterial Switch Operation.......e207
8.4.1. Definition and Associated Lesions.......e207
8.4.2. Clinical Course.......e207
8.4.3. Clinical Features and Evaluation After Arterial Switch Operation.......e208
8.4.4. Surgical and Catheterization-Based Intervention.......e208
8.5. Recommendations for Congenital Coronary Anomalies of Ectopic Arterial Origin.......e208
8.5.1. Definition, Associated Lesions, and Clinical Course.......e208
8.5.2. Clinical Features and Evaluation of the Unoperated Patient.......e208
22.214.171.124. Preintervention Evaluation.......e208
8.5.3. Management Strategies.......e208
126.96.36.199. Surgical and Catheterization-Based Intervention.......e208
8.6. Recommendations for Anomalous Left Coronary Artery From the Pulmonary Artery.......e209
8.6.1. Definition and Associated Lesions and Clinical Course.......e209
8.7. Management Strategies.......e209
8.7.1. Surgical Intervention.......e209
8.7.2. Surgical and Catheterization-Based Intervention.......e209
8.8. Recommendations for Coronary Arteriovenous Fistula.......e209
8.8.2. Clinical Course.......e210
8.8.3. Preintervention Evaluation.......e210
8.9. Recommendations for Management Strategies.......e210
8.9.1. Surgical Intervention.......e210
8.9.2. Catheterization-Based Intervention.......e210
8.9.3. Preintervention Evaluation After Surgical or Catheterization-Based Repair.......e210
9. Pulmonary Hypertension/Eisenmenger Physiology.......e210
9.2. Clinical Course.......e211
9.2.1. Dynamic Congenital Heart Disease–Pulmonary Arterial Hypertension.......e211
9.2.2. Immediate Postoperative Congenital Heart Disease–Pulmonary Arterial Hypertension.......e211
9.2.3. Late Postoperative Congenital Heart Disease–Pulmonary Arterial Hypertension.......e211
9.2.4. Normal to Mildly Abnormal Pulmonary Vascular Resistance States.......e211
9.2.5. Eisenmenger Physiology.......e212
9.3. Problems and Pitfalls.......e212
9.4. Recommendations for Evaluation of the Patient With Congenital Heart Disease–Pulmonary Arterial Hypertension.......e212
9.4.1. Dynamic Congenital Heart Disease–Pulmonary Arterial Hypertension.......e212
9.4.2. Eisenmenger Physiology.......e213
9.5. Management Strategies.......e213
9.5.1. Recommendations for Medical Therapy of Eisenmenger Physiology.......e213
9.6. Key Issues to Evaluate and Follow-Up.......e214
9.6.1. Recommendations for Reproduction.......e214
9.6.3. Other Interventions.......e215
9.6.4. Recommendations for Follow-Up.......e215
9.6.5. Endocarditis Prophylaxis.......e215
10. Tetralogy of Fallot.......e215
10.1. Definition and Associated Lesions.......e215
10.2. Clinical Course (Unrepaired).......e215
10.2.1. Presentation as an Unoperated Patient.......e215
10.2.2. Postsurgical Presentation.......e215
10.3. Clinical Features and Evaluation.......e215
10.3.1. Clinical Examination.......e215
10.3.3. Chest X-Ray.......e216
10.3.4. Initial Surgical Repair.......e216
10.4. Recommendations for Evaluation and Follow-Up of the Repaired Patient.......e216
10.4.1. Recommendation for Imaging.......e217
10.5. Recommendations for Diagnostic and Interventional Catheterization for Adults With Tetralogy of Fallot.......e217
10.5.1. Branch Pulmonary Artery Angioplasty.......e217
10.5.2. Exercise Testing.......e218
10.5.3. Diagnostic Catheterization.......e218
10.6. Problems and Pitfalls in the Patient With Prior Repair.......e218
10.7. Management Strategy for the Patient With Prior Repair.......e218
10.7.1. Medical Therapy.......e218
10.8. Recommendations for Surgery for Adults With Previous Repair of Tetralogy of Fallot.......e218
10.8.1. Recommendations for Interventional Catheterization .......e219
10.9. Key Issues to Evaluate and Follow-Up .......e219
10.9.1. Recommendations for Arrhythmias: Pacemaker/Electrophysiology Testing.......e219
10.9.4. Endocarditis Prophylaxis.......e221
11. Dextro-Transposition of the Great Arteries.......e221
11.2. Associated Lesions.......e221
11.3. Clinical Course: Unrepaired.......e221
11.4. Recommendation for Evaluation of the Operated Patient With Dextro-Transposition of the Great Arteries.......e221
11.4.1. Clinical Features and Evaluation of Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure.......e222
11.4.2. Clinical Examination.......e222
11.4.4. Imaging for Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure.......e222
188.8.131.52. Recommendations for Imaging for Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure.......e222
11.4.5. Cardiac Catheterization.......e223
11.5. Clinical Features and Evaluation of Dextro-Transposition of the Great Arteries After Arterial Switch Operation.......e223
11.5.1. Clinical Examination.......e223
11.5.3. Chest X-Ray.......e223
11.5.4. Recommendations for Imaging for Dextro-Transposition of the Great Arteries After Arterial Switch Operation.......e223
11.5.5. Recommendation for Cardiac Catheterization After Arterial Switch Operation.......e223
11.6. Clinical Features and Evaluation: Dextro-Transposition of the Great Arteries After Rastelli Operation.......e224
11.6.2. Chest X-Ray.......e224
11.7. Recommendations for Diagnostic Catheterization for Adults With Repaired Dextro-Transposition of the Great Arteries.......e224
11.7.1. Problems and Pitfalls.......e224
11.8. Management Strategies.......e224
11.8.1. Medical Therapy.......e224
11.8.2. Recommendations for Interventional Catheterization for Adults With Dextro-Transposition of the Great Arteries.......e224
184.108.40.206. Interventional Catheter Options After Atrial Baffle.......e225
220.127.116.11. Interventional Catheter Options After Arterial Switch Operation.......e225
18.104.22.168. Interventional Catheter Options After Rastelli Repair.......e225
11.8.3. Recommendations for Surgical Interventions.......e225
22.214.171.124. After Atrial Baffle Procedure (Mustard, Senning) .......e225
126.96.36.199. After Arterial Switch Operation.......e225
188.8.131.52. After Rastelli Procedure.......e225
184.108.40.206. Reoperation After Atrial Baffle Procedure.......e226
220.127.116.11. Reoperation After Arterial Switch Operation.......e226
18.104.22.168. Reoperation After Rastelli Repair.......e226
22.214.171.124. Other Reoperation Options.......e227
11.9. Recommendations for Electrophysiology Testing/Pacing Issues in Dextro-Transposition of the Great Arteries.......e227
11.10. Key Issues to Evaluate and Follow-Up.......e227
11.10.1. Recommendations for Endocarditis Prophylaxis.......e227
11.10.2. Recommendation for Reproduction.......e228
11.10.3. Activity and Exercise.......e228
12. Congenitally Corrected Transposition of the Great Arteries.......e228
12.2. Associated Lesions.......e228
12.3. Clinical Course.......e228
12.3.1. Presentation in Adulthood: Unoperated.......e228
12.4. Clinical Features and Evaluation of the Unoperated Patient.......e229
12.4.1. Clinical Examination.......e229
12.4.3. Exercise Testing.......e229
12.4.4. Chest X-Ray.......e230
12.4.5. Two-Dimensional Echocardiography.......e230
12.4.6. Magnetic Resonance Imaging.......e230
12.4.7. Cardiac Catheterization.......e230
12.5. Recommendations for Evaluation and Follow-Up of Patients With Congenitally Corrected Transposition of the Great Arteries.......e230
12.6. Key Issues of Unoperated Patients.......e230
12.7. Management Strategies.......e231
12.8. Interventional Therapy.......e231
12.8.1. Recommendations for Catheter Interventions.......e231
12.8.2. Initial Surgical Repair.......e231
12.8.3. Recommendations for Surgical Intervention.......e231
12.8.4. Problems and Pitfalls.......e232
12.9. Arrhythmias/Pacemaker/Electrophysiology Testing.......e232
12.10. Recommendations for Postoperative Care.......e232
12.10.1. Recommendations for Endocarditis Prophylaxis.......e232
12.10.2. Recommendation for Reproduction.......e233
13. Ebstein's Anomaly.......e233
13.2. Clinical Course (Unoperated).......e233
13.2.1. Pediatric Presentation.......e233
13.2.2. Initial Adult Presentation.......e233
13.3. Clinical Features and Evaluation of the Unoperated Patient.......e233
13.4. Recommendation for Evaluation of Patients With Ebstein's Anomaly.......e234
13.4.1. Clinical Examination.......e234
13.4.3. Chest X-Ray.......e234
13.4.5. Magnetic Resonance Imaging/Computed Tomography.......e234
13.5. Recommendations for Diagnostic Tests.......e234
13.5.1. Cardiac Catheterization.......e235
13.5.2. Problems and Pitfalls.......e235
13.6. Management Strategies.......e235
13.6.1. Recommendation for Medical Therapy.......e235
13.6.2. Physical Activity.......e235
13.7. Recommendation for Catheter Interventions for Adults With Ebstein's Anomaly.......e235
13.7.1. Recommendation for Electrophysiology Testing/Pacing Issues in Ebstein's Anomaly.......e235
13.7.2. Recommendations for Surgical Interventions.......e235
13.7.3. Postoperative Findings.......e236
13.7.4. Expected Postoperative Course.......e236
13.8. Problems and Pitfalls.......e236
13.9. Recommendation for Reproduction.......e236
13.10. Recommendation for Endocarditis Prophylaxis.......e237
14. Tricuspid Atresia/Single Ventricle.......e237
14.2. Clinical Course (Unoperated and Palliated).......e237
14.3. Clinical Features and Evaluation of the Unoperated or Palliated Patient.......e237
14.3.2. Clinical Examination.......e237
14.3.4. Chest X-Ray.......e238
14.3.6. Magnetic Resonance Imaging/Computed Tomography.......e238
14.3.7. Recommendation for Catheterization Before Fontan Procedure.......e238
14.4. Recommendation for Surgical Options for Patients With Single Ventricle.......e238
14.5. Recommendation for Evaluation and Follow-Up After Fontan Procedure.......e239
14.6. Clinical Features and Evaluation.......e240
14.6.1. Clinical Examination.......e240
14.6.3. Chest X-Ray.......e240
14.6.4. Recommendation for Imaging.......e240
14.7. Recommendation for Diagnostic and Interventional Catheterization After Fontan Procedure.......e240
14.7.1. Evaluation of Patients With Protein-Losing Enteropathy.......e240
14.7.2. Problems and Pitfalls.......e241
14.8. Recommendations for Management Strategies for the Patient With Prior Fontan Repair.......e241
14.8.1. Recommendations for Medical Therapy.......e241
14.9. Recommendations for Surgery for Adults With Prior Fontan Repair.......e241
14.10. Key Issues to Evaluate and Follow-Up.......e242
14.10.1. Recommendations for Electrophysiology Testing/Pacing Issues in Single-Ventricle Physiology and After Fontan Procedure.......e242
14.10.2. Other Issues to Evaluate and Follow-Up.......e243
14.10.3. Recommendations for Endocarditis Prophylaxis.......e243
14.10.5. Recommendations for Reproduction.......e244
Appendix 1. Author Relationships With Industry and Other Entities.......e244
Appendix 2. Peer Reviewer Relationships With Industry and Other Entities.......e245
Appendix 3. Abbreviations List.......e247
Appendix 4. Definitions of Surgical Procedures for the Management of Adults With CHD.......e247
It is important that the medical profession play a central role in critically evaluating the use of diagnostic procedures and therapies introduced and tested for detection, management, or prevention of disease. Rigorous, expert analysis of the available data documenting absolute and relative benefits and risks of these procedures and therapies can produce guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the cost of care by focusing resources on the most effective strategies.
The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of guidelines in the area of cardiovascular disease since 1980. The American College of Cardiology (ACC)/AHA Task Force on Practice Guidelines is charged with developing, updating, and revising practice guidelines for cardiovascular diseases and procedures and directs this effort. Writing committees are charged with assessing the evidence as an independent group of authors to develop, update, or revise recommendations for clinical practice.
Experts in the subject under consideration have been selected from both organizations to examine subject-specific data and write guidelines in partnership with representatives from other medical practitioner and specialty groups. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against particular treatments or procedures, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of tests or therapies are considered, as well as the frequency of follow-up and cost-effectiveness. When available, information from studies on cost is considered, but data on efficacy and clinical outcomes constitute the primary basis for recommendations in these guidelines.
The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid actual, potential, or perceived conflicts of interest that might arise as a result of industry relationships or personal interests among the writing committee. Specifically, all members of the writing committee, as well as peer reviewers of the document, are asked to disclose all such relationships that might be perceived as real or potential conflicts of interest. Writing committee members are also strongly encouraged to declare previous relationships with industry that might be perceived as relevant to guideline development. If a writing committee member develops a new relationship with industry during their tenure, they are required to notify guideline staff in writing. These statements are reviewed by the parent task force, reported orally to all members at each meeting of the writing committee, and updated and reviewed by the writing committee as changes occur. Please refer to the methodology manual for ACC/AHA guideline writing committees for further description of the relationships with industry policy (1). See Appendix 1 for author relationships with industry and Appendix 2 for peer reviewer relationships with industry 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 diagnosis, management, and prevention of specific diseases or conditions. Clinicians should consider the quality and availability of expertise in the area where care is provided. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. The recommendations reflect a consensus of expert opinion after a thorough review of the available current scientific evidence and are intended to improve patient care.
Patient adherence to prescribed and agreed upon medical regimens and lifestyles is an important aspect of treatment. Prescribed courses of treatment in accordance with these recommendations are only effective if they are followed. Because lack of patient understanding and adherence may adversely affect outcomes, physicians and other healthcare providers should make every effort to engage the patient's active participation in prescribed medical regimens and lifestyles.
If these guidelines are used as the basis for regulatory or payer decisions, the goal is quality of care and serving the patient's best interest. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and the patient in light of all of the circumstances presented by that patient. There are circumstances in which deviations from these guidelines are appropriate.
The guidelines will be reviewed annually by the ACC/AHA Task Force on Practice Guidelines and considered current unless they are updated, revised, or withdrawn from distribution. The executive summary and recommendations are published in the December 2, 2008, issue of the Journal of the American College of Cardiology and December 2, 2008, issue of Circulation. The full-text guidelines are e-published in the same issue of these journals and posted on the ACC (www.acc.org) and AHA (htttp://my.americanheart.org) World Wide Web sites.
Sidney C. Smith, Jr, MD, FACC, FAHA
Chair, ACC/AHA Task Force on Practice Guidelines
1.1. Methodology and Evidence Review
The recommendations listed in this document are, whenever possible, evidence-based. Unlike other ACC/AHA practice guidelines, there is not a large body of peer-reviewed published evidence to support most recommendations, which will be clearly indicated in the text. An extensive literature survey was conducted that led to the incorporation of 647 references. Searches were limited to studies, reviews, and other evidence conducted in human subjects and published in English. Key search words included but were not limited to adult congenital heart disease (ACHD), atrial septal defect, arterial switch operation, bradycardia, cardiac catheterization, cardiac reoperation, coarctation, coronary artery abnormalities, cyanotic congenital heart disease, Doppler-echocardiography, d-transposition of the great arteries, Ebstein's anomaly, Eisenmenger physiology, familial, heart defect, medical therapy, patent ductus arteriosus, physical activity, pregnancy, psychosocial, pulmonary arterial hypertension, right heart obstruction, supravalvular pulmonary stenosis, surgical therapy, tachyarrhythmia, tachycardia, tetralogy of Fallot, transplantation, tricuspid atresia, and Wolff-Parkinson-White. Additionally, the writing committee reviewed documents related to the subject matter previously published by the ACC and AHA. References selected and published in this document are representative and not all-inclusive.
The committee reviewed and ranked evidence supporting current recommendations with the weight of evidence ranked as Level A if the data were derived from multiple randomized clinical trials involving a large number of individuals. The committee ranked available evidence as Level B when data were derived from a limited number of trials involving a comparatively small number of patients or from well-designed data analyses of nonrandomized studies or observational data registries. Evidence was ranked as Level C when the consensus of experts was the primary source of the recommendation. In the narrative portions of these guidelines, evidence is generally presented in chronological order of development. Studies are identified as observational, randomized, prospective, or retrospective. The committee emphasizes that for certain conditions for which no other therapy is available, the indications are based on expert consensus and years of clinical experience and are thus well supported, even though the evidence was ranked as Level C. An analogous example is the use of penicillin in pneumococcal pneumonia where there are no randomized trials and only clinical experience. When indications at Level C are supported by historical clinical data, appropriate references (eg, case reports and clinical reviews) are cited if available. When Level C indications are based strictly on committee consensus, no references are cited. The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in ACHD patients summarize both clinical evidence and expert opinion. The schema for classification of recommendations and level of evidence is summarized in Table 1, which also illustrates how the grading system provides an estimate of the size of treatment effect and an estimate of the certainty of the treatment effect.
1.2. Organization of Committee and Relationships With Industry
The ACC/AHA Task Force on Practice Guidelines was formed to create clinical practice guidelines for select cardiovascular conditions with important implications for public health. This guideline writing committee was assembled to adjudicate the evidence and construct recommendations regarding the diagnosis and treatment of ACHD. Writing committee members were selected with attention to ACHD subspecialties, broad geographic representation, and involvement in academic medicine and clinical practice. The writing committee included representatives of the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
All members of the writing committee were required to disclose all relationships with industry relevant to the data under consideration (1).
1.3. Document Review and Approval
This document was reviewed by 3 external reviewers nominated from both the ACC and the AHA, as well as reviewers from the American Society of Echocardiography, Canadian Cardiovascular Society, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, and Society of Thoracic Surgeons, and 20 individual content reviewers which included reviewers from the ACC Congenital Heart Disease and Pediatric Cardiology Committee and the AHA Congenital Cardiac Defects Committee. All reviewer relationships with industry information were collected and distributed to the writing committee and are published in this document (see Appendix 2 for details).
This document was approved for publication by the governing bodies of the ACCF and the AHA and endorsed by the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
1.4. Epidemiology and Scope of the Problem
Remarkable improvement in survival of patients with congenital heart disease (CHD) has occurred over the past half century since reparative surgery has become commonplace. Since the advent of neonatal repair of complex lesions in the 1970s, an estimated 85% of patients survive into adult life. The 32nd Bethesda Conference report in 2000 estimated that there were approximately 800 000 adults with CHD in the United States (2,3). Given modern surgical mortality rates of less than 5%, one would expect that in the next decade, almost 1 in 150 young adults will have some form of CHD. In particular, there are a substantial number of young adults with single-ventricle physiology, systemic right ventricles (RVs), or complex intracardiac baffles who are now entering adult life and starting families. Young adults have many psychological, social, and financial issues that present barriers to proactive health management. The infrastructure that is provided to most pediatric cardiology centers, namely, case management by advanced practice nurses and social workers, is largely lacking within the adult healthcare system. Recognizing the compound effects of a complex and unfamiliar disease with an unprepared patient and healthcare system, the ACC/AHA ACHD Guideline Writing Committee has determined that the most immediate step it can take to support the practicing cardiologist in the care of ACHD patients is to provide a consensus document that outlines the most important diagnostic and management strategies and indicates when referral to a highly specialized center is appropriate. To provide ease of use, the writing committee constructed this document by lesion type and in each section included recommendations on topics common to all lesions (eg, infective endocarditis [IE] prophylaxis, pregnancy, physical activity, and medical therapy).
1.5. Recommendations for Delivery of Care and Ensuring Access
1. The focus of current healthcare access goals for ACHD patients should include the following:
a. Strengthening organization of and access to transition clinics for adolescents and young adults with CHD, including funding of allied healthcare providers to provide infrastructure comparable to that provided for children with CHD. (Level of Evidence: C)
b. Organization of outreach and education programs for patients, their families, and caregivers to recapture patients leaving pediatric supervisory care or who are lost to follow-up. Such programs can determine when and where further intervention is required. (Level of Evidence: C)
c. Enhanced education of adult cardiovascular specialists and pediatric cardiologists in the pathophysiology and management of ACHD patients. (Level of Evidence: C)
d. A liaison with regulatory agencies at the local, regional, state, and federal levels to create programs commensurate with the needs of this large cardiovascular population. (Level of Evidence: C)
2. Health care for ACHD patients should be coordinated by regional ACHD centers of excellence that would serve as a resource for the surrounding medical community, affected individuals, and their families (Table 2).⇓
a. Every academic adult cardiology/cardiac surgery center should have access to a regional ACHD center for consultation and referral. (Level of Evidence: C)
b. Each pediatric cardiology program should identify the ACHD center to which the transfer of patients can be made. (Level of Evidence: C)
c. All emergency care facilities should have an affiliation with a regional ACHD center. (Level of Evidence: C)
3. ACHD patients should carry a complete medical “passport” that outlines specifics of their past and current medical history, as well as contact information for immediate access to data and counsel from local and regional centers of excellence. (Level of Evidence: C)
4. Care of some ACHD patients is complicated by additional special needs, including but not restricted to intellectual incapacities or psychosocial limitations that necessitate the inclusion of designated healthcare guardians in all medical decision making. (Level of Evidence: C)
5. Every ACHD patient should have a primary care physician. To ensure and improve communication, current clinical records should be on file with the primary care physician and a local cardiovascular specialist, as well as at a regional ACHD center; patients should also have copies of relevant records. (Level of Evidence: C)
6. Every cardiovascular family caregiver should have a referral relationship with a regional ACHD center so that all patients have geographically accessible care. (Level of Evidence: C)
The need for delivery of appropriate healthcare to ACHD patients largely remains unmet. The 32nd Bethesda Conference report in 2000 recommended organizing ACHD care within a regional and national system of specialized adult CHD centers of excellence that would disseminate care, provide education, orchestrate research and innovation, and serve as a general resource for the region within this model (3) (Table 2). Such a system has been demonstrated to improve care for adults with similar chronic severe illness, such as severe heart failure, for which measures of improvement surrounding uniformity of care within a guidelines framework, medical and surgical outcomes, decreased visits, improved patient quality of life, cost containment, data collection and knowledge dissemination, trials of new therapeutics, and enhanced insurability have been achieved.
A detailed integration of caregivers and support was suggested by the 32nd Bethesda Conference, from primary care to patient advocacy groups to the highest levels of subspecialty resources. The pediatric cardiology team should be paired with adult cardiologists to facilitate transition of care for affected individuals. It was recommended that all ACHD patients have a provider who constitutes the medical “home,” as well as at least 1 overreaching visit with a cardiologist with advanced training and experience with ACHD patients (4). A pattern of visits, follow-up, surgical care, subspecialty (catheterization, electrophysiology) cardiac and noncardiac care, emergent medical access, data coordination and dissemination, referral guidance, and education (with recognized regional variation) was suggested for ACHD patients and their caregivers based on the degree of medical complexity. Improvement in patient outcome was stressed via extension of physician caregiving by team-based clinical care associates (midlevel practitioners) with expertise in the management of ACHD patients.
The 32nd Bethesda Conference described 3 levels of training of adult cardiovascular specialists in terms of experience in ACHD (5). Task Force 9 covered training in the care of adult patients with CHD and differentiated 3 levels of training and expected expertise. These levels were subsequently incorporated into the COCATS (Core Cardiology Training Symposium) III document (6). Level 1 training consists of basic exposure to CHD patients and organized educational material on CHD. To enable proper recognition of the problems of adults with CHD and to be cognizant of when specialized referral is needed, all medical cardiology fellows should achieve level 1 training in CHD. Level 1 trainees should be instructed by a faculty member with level 2 or 3 training or its equivalent. A pediatric cardiologist should also be involved in these training programs.
Level 2 training represents additional training for fellows who plan to care for adult patients with CHD so that they may acquire expertise in the clinical evaluation and management of such patients. Level 2 training generally requires 1 year of training in ACHD: either a 1-year formal program at a regional or tertiary care ACHD center or cumulative experience of 12 months through repetitive rotations or electives as a cardiology fellow with experienced ACHD cardiologists. This training should prepare the individual to be well-equipped for the routine care of even moderate to complex ACHD and to recognize when more advanced consultation or referral is advisable.
Level 3 training represents the level of knowledge needed by those graduates who wish to make a clinical and academic/research commitment to this field and not only become competent in the care of the entire spectrum of adult patients with CHD but also participate in the teaching and research of ACHD. Level 3 trainees generally require 2 years of training. These 24 months may either be consecutive or cumulative experience, and some recognition can be given to overall experience in CHD, be it pediatric, adolescent, or adult (eg, prior pediatric cardiology training or rotations). Such level 3 training would be sufficient to clinically manage the most complex ACHD patient in a regional or tertiary care center, to pursue an academic career, to train others in the field, or to direct an ACHD center program (6).
The 32nd Bethesda Conference report in 2000 highlighted the need for healthcare professionals, patients, and their families, together with regulatory agency representatives, to develop a strategic plan for organized advocacy for ACHD patients (3,4). This ACC/AHA Guideline Committee, working in parallel with but independently of a workgroup of the National Heart, Lung, and Blood Institute charged with recommending key research opportunities in ACHD patients, recognizes key actions that are currently and urgently required to improve care access for ACHD patients.
1.5.1. Recommendations for Access to Care
1. An individual primary caregiver or cardiologist without specific training and expertise in ACHD should manage the care of adults with complex and moderate CHD (Tables 3 and 4)⇓⇓(7) only in collaboration with level 2 or level 3 ACHD specialists. (4) (Level of Evidence: C)
2. For ACHD patients in the lowest-risk group (simple CHD;Table 5),⇓cardiac follow-up at a regional ACHD center is recommended at least once to formulate future needs for follow-up. (Level of Evidence: C)
3. Frequent follow-up (generally every 12 to 24 months) at a regional ACHD center is recommended for the larger group of adults with complex and moderate CHD. A smaller group of adults with very complex CHD will require follow-up at a regional ACHD center at a minimum of every 6 to 12 months. (Level of Evidence: C)
4. Stabilized adult patients with CHD who require admission for urgent or acute care should be transferred to a regional ACHD center, except in some circumstances after consultation with the patient's primary level 2 or level 3 ACHD specialist. (4) (Level of Evidence: C)
5. Diagnostic and interventional procedures, including imaging (ie, echocardiography, magnetic resonance imaging [MRI], or computed tomography [CT]), advanced cardiac catheterization, and electrophysiology procedures for adults with complex and moderate CHD should be performed in a regional ACHD center with appropriate experience in CHD and in a laboratory with appropriate personnel and equipment. Personnel performing such procedures should work as part of a team with expertise in the surgical and transcatheter management of patients with CHD. (Level of Evidence: C)
6. Surgical procedures that require general anesthesia or conscious sedation in adults with moderate or complex CHD should be performed in a regional ACHD center with an anesthesiologist familiar with ACHD patients. (Level of Evidence: C)
7. ACHD patients should be transferred to an ACHD center for urgent or acute care of cardiac problems. (Level of Evidence: C)
8. Adult patients with complex or high-risk CHD should be transferred to an ACHD center for urgent or acute noncardiac problems. (Level of Evidence: C)
9. An ACHD specialist should be notified or consulted when a patient with simple or low-risk CHD is admitted to a non-ACHD center. (Level of Evidence: C)
After leaving the pediatric healthcare system, a percentage of ACHD patients do not succeed in achieving continuous cardiovascular care (8,9). Accordingly, ACHD patients are underserved compared with other heart disease populations. Barriers to healthcare access exist for ACHD patients, including the following:
• Failure to have guided transition from pediatric to adult care
• Lack of sufficient numbers of specialty clinics and regional centers
• Inadequate access to or availability of insurance (10)
• Insufficient education of patients and caregivers regarding disease nature and follow-up (11,12)
• Inadequate system of management of patient's cognitive or psychosocial impairment
• Inadequate infrastructure for case management.
1.5.2. Recommendations for Psychosocial Issues
1. Individual and family psychosocial screening (including knowledge assessment of cardiac disease and management; perceptions about health and the impact of CHD; social functioning with family, friends, and significant others; employment and insurability status; and screening for cognitive, mood, and psychiatric disorders) should be part of the care of ACHD patients. Advanced practice nurses, physician assistants, psychologists, and social workers should play an integral role in assessing and providing for the psychosocial needs of ACHD patients. (Level of Evidence: C)
2. Informational tools should be developed before transfer from adolescent to adult care and used for patient/family education regarding CHD, including the following elements, to be provided in electronic format:
a. Demographic data, including physician contact. (Level of Evidence: C)
b. Description of CHD, surgeries, interventional procedures, and most recent diagnostic studies. (Level of Evidence: C)
c. Medications. (Level of Evidence: C)
3. Additional health maintenance screening and information should be offered to ACHD patients as indicated during each visit to their ACHD healthcare provider, including the following:
a. Endocarditis prophylaxis measures (refer to Section 1.6, Recommendations for Infective Endocarditis). (Level of Evidence: C)
b. Exercise prescription, guidelines for exercise, and athletic participation for patients with CHD should reflect the published recommendations of the 36th Bethesda Conference report. (5) (Level of Evidence: C)
c. Contraception and pregnancy information, including education regarding risk of CHD in offspring (for men and women). (Level of Evidence: C)
d. General medical/dental preventive care (eg, smoking cessation, weight loss/maintenance, hypertension/lipid screening, oral care, and substance abuse counseling). (Level of Evidence: C)
e. Recommended follow-up with cardiology. (Level of Evidence: C)
4. Vocational referral and health insurance information should be offered to ACHD patients during the transition period and refreshed at the time of their initial consultation in a tertiary referral center and intermittently as indicated by their social situation. (Level of Evidence: C)
5. A formal transition process should be used to provide optimal transfer of patients into ACHD care. This process should begin by 12 years of age and should be individualized on the basis of the patient's maturity level, with the goal being to transition and ultimately transfer the patient into adult care settings depending on the stability of the disease and psychosocial status. (Level of Evidence: C)
6. A psychological evaluation should be obtained if an adult's mental competency is in question and no appointed adult surrogate is available. (Level of Evidence: C)
7. All ACHD patients should be encouraged to complete an advance directive, ideally at a time during which they are not extremely ill or hospitalized, so that they can express their wishes thoughtfully in a less stressful setting and communicate these wishes to their families and caregivers. (Level of Evidence: C)
The degree of psychological impact caused by CHD remains ill defined. Results from decades of literature are divided with regard to the psychological functioning of ACHD patients. Methodologically, the challenges of controlling for medical, social, demographic, genetic, and cognitive variables that interact with psychological development make it difficult to draw general conclusions from studies (13,14); however, important clues regarding psychosocial outcomes have been useful in guiding medical therapy and thus form the foundation for comprehensive management of ACHD patients.
Early studies of psychosocial function dealt only with children and often reflected populations that confronted unrepaired CHD for longer periods of time. Thus, research focused on the “sick child” and recognized a recurrent theme of parental overprotection, as well as profiling the effect CHD had on the family unit (15,16). Maternal perceptions, accurate or not, were far more closely correlated to maladjustment in children than was medical severity of the child's illness (13,17). Intuitively, the psychopathology of children with CHD, imparted by physiological stress during early childhood, disruption of family dynamics, altered school and peer structure, and other unmet childhood milestones, may leave cognitive and psychological marks that carry over into adult life. Although there is evidence that argues for earlier reparative surgery to minimize childhood insecurities and morbidity (18), a correlation between the severity of CHD and psychological adjustment has not been substantiated (16,17,19–22). Moreover, new information is emerging about cognitive functioning in adolescents who underwent surgical repair in infancy with cardiopulmonary bypass that indicates some deficits in planning and self-management (23–27). Long-term behavioral outcome studies after the neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA) have demonstrated highly specific disabilities that might impact the quality of self-care (28). Longer survival and decreasing morbidity among ACHD patients has made quality-of-life issues much more central to the understanding and management of this population (14,29–39). Some quality-of-life issues pertinent to ACHD patients, regardless of severity of disease, include independent living arrangements, education, employment, sports, health and life insurance acquisition, contraception, genetic counseling, and pregnancy concerns (40).
Circumstantial depression and anxiety are understandable in older adolescents and young adults with chronic health problems. One pilot study suggests that up to one third of ACHD patients may have a psychiatric disorder, with depression and anxiety being most prominent (41), whereas only 20% of the general population are afflicted with psychiatric illness (42). Accordingly, a careful assessment of depressive symptoms and their possible overlap with symptoms of medical illness or side effects of medications must be part of the clinical evaluation of ACHD patients (13,14).
1.5.3. Transition of Care
Physical and emotional maturity is the primary requirement for transfer of adolescent or young adult patients into adult care environments. The age at which this occurs varies and may range from the mid-teens to the mid-20s, depending on the patient. However, the process of transitioning, that is, preparing young patients for successful transfer to an adult healthcare provider at a later time, should begin by the age of 12 years (43).
Strategies for transfer of patients with CHD into adult care settings are well described (44,45) and use a stepwise approach to establishing autonomy and understanding one's cardiac problem and lifestyle issues important to long-term stability of CHD. Pediatric clinicians can reinforce autonomy by focusing their communication on the patient, so that the teen years serve as an ongoing “workshop” in which the ultimate goal is accepting ownership of and responsibility for one's cardiac disease. Parents should take an active role in fostering independence in their teenagers. The use of support groups and educational meetings geared toward parents and ACHD patients offers a prime opportunity for parents to discuss their fears and openly communicate reality-based strategies for approaching difficult topics with their children. National support organizations for CHD and ACHD patients now exist and provide resources for families (eg, the Congenital Heart Information Network and the Adult Congenital Heart Association). Regional tertiary centers for the care of ACHD patients may also provide conferences that serve this purpose. Some centers provide transitional support meetings so that adolescents and parents can familiarize themselves with the goals of ACHD care. Despite the availability of structured resources for parents, patients, and families with CHD, the ultimate responsibility still rests with clinicians to meet the educational needs of their young patients. Topics that should be discussed early in childhood and repeatedly through the teens, 20s, and beyond include a description of the cardiac defect and surgeries (including use of diagrams); medications; exercise prescription; risk modification; health maintenance and follow-up recommendations; vocational and educational recommendations; insurance information; and information about genetics, contraception, and pregnancy. This information should be given in verbal and written form and provided to the patient in an electronic or paper format (45,46). This is a reference tool that can be a constant resource for the patient long term and can assist healthcare providers who are not familiar with the patient. The use of advanced practice nurses and physician assistants in pediatric and ACHD settings optimizes the facilitation of the transition process from pediatrics to adult cardiology, identification of patient needs, screening and referral for psychosocial problems, and education and counseling of patients and families (47).
Pertinent medical records, including diagrams of cardiac defects and operations, operative and procedural reports, recent physical examination, electrocardiograms (ECGs), and echocardiograms, should be provided to all cardiologists involved in the care of a patient with CHD. In addition, once patients are properly educated and aware of basic terminology pertaining to their own cardiac status, they should be offered copies of their medical reports, which implies and imparts responsibility and autonomy regarding their condition.
1.5.4. Exercise and Athletics
Exercise restrictions correlate with internalization of fear in young people with CHD (48). The ability to exercise is a fundamental measure of quality of life, perceived capacity for social acceptance, employment, sexual relations, and procreation. Young people with CHD may experience exercise limitations for many reasons, including their underlying cardiac reserve, physical deconditioning, and lack of exercise experience in childhood; poor coordination related to coexisting disabilities; misperceptions about restrictions; lack of interest; and anxiety (43,44). Current symptoms only account for approximately 30% of all barriers to exercise. Recommendations regarding physical training, exercise, and athletics are core to the comprehensive patient education that should begin by early adolescence. An individual exercise prescription (one that accounts for physical limitations, developmental challenges, risk modification, health concerns such as obesity, and personal preferences) needs to be provided and updated regularly so that the beneficial utility of exercise is not lost among a list of restrictions. Guidelines for physical activity and exercise in patients with CHD are outlined in the 36th Bethesda Conference in “Eligibility: Recommendations for Competitive Athletes with Cardiovascular Abnormalities.” (49) Currently, however, there are few data concerning activity guidelines for the nonathlete.
The finding of diminished aerobic capacity in all groups with CHD (50–58) validates the importance of comparative testing over time in patients until reference values can be researched further (54). However, improved oxygen uptake during exercise is only 1 parameter of the effect of training and cannot be used alone to determine whether the main goals of exercise have been achieved (59). Beyond improved oxygen consumption and tolerance of physical activity, physical training of children and adolescents can also result in decreased withdrawal and somatic complaints (60,61). This supports the need for organized exercise programs for young people with CHD, particularly adolescents who view physical activity as the defining focus of a healthy lifestyle despite restrictions from competitive athletics.
Entering the job market and establishing a career is arguably the most important developmental milestone of a young adult's life (30). Careful consideration of the individual's physical, mental, and psychological disposition will help in identifying the right career choice. This is a discussion that should include the cardiologist, so that realistic limitations are explored and misconceptions eliminated. Vocational planning should take place early in adolescence so that appropriate educational options can be pursued long before the patient enters the work force. Ideally, cognitive evaluation should be performed at or before 5 years of age so that the appropriate educational track can be determined. Early childhood intervention has been shown to result in improved employment status during adult life (62). The goal of clinicians caring for those with CHD should be to view every patient as employable and avoid the temptation to accept the status quo when a patient is receiving social security disability income or other disability assistance through Medicaid or Medicare. Governmental assistance programs may perpetuate long-term disability for those fearful of losing their health insurance coverage (63). Reports from more than a decade ago projected that approximately 10% of ACHD patients would be totally disabled (64). Furthermore, 8% to 13% of ACHD patients were receiving public assistance or living as a dependent with relatives (64,65). Important legislation has focused on bringing individuals with disabilities into the work force. Ultimately, with improving longevity in patients with CHD and better surgical outcomes, the proportion of physically disabled ACHD patients is expected to decrease.
Seeking assistance from the state employment development department (the names of these programs vary from state to state) can be an important step in finding jobs for adults with disabilities. These programs offer job and training referrals, counseling, and job search assistance and workshops. Federal programs provide for vocational rehabilitation for disabled individuals, as well as hiring and placement into jobs appropriate for their level of disability.
The Americans With Disabilities Act of 1990 prohibits discrimination with respect to hiring, promotion, or termination of employees on the basis of disability. Therefore, ACHD patients are not required to disclose their cardiac condition to a prospective employer unless physical restrictions imposed by their cardiac disease would limit their ability to satisfy the job description (63). The Family and Medical Leave Act of 1993 states that covered employers must grant eligible employees up to a total of 12 workweeks of unpaid leave during any 12-month period when the employee is unable to work because of a serious health condition or to take care of an immediate family member with a serious health condition (66).
The Work Incentives Improvement Act of 1999 (also known as the Medicaid Buy-In Program) is designed to promote employment and economic self-sufficiency for individuals with disabilities. Under this federal legislation, states can amend their Medicaid programs to enable individuals with disabilities to obtain coverage under Medicaid while giving incentives for these individuals to seek and maintain employment. Advocates in each ACC and AHA chapter should work with state Medicaid programs and state legislators to define appropriate health disabilities eligible for coverage (10).
In the 1990s, studies indicated that up to 20% of ACHD patients were uninsured and that most health insurance policies were individual plans rather than group policies. The heterogeneity of CHD over the life span contributes to the difficulties faced by insurers when assigning risk. Regional tertiary centers specializing in the care of ACHD patients must collaborate in multicenter studies to define and publish survival data in a format amenable to life-table analysis (67). In addition, the use of clinical practice guidelines, such as those outlined in this ACC/AHA document, will further direct insurers, primary care providers, and cardiologists on the appropriate use of diagnostic testing, as well as the appropriate time for referral.
Today, the most affordable way to obtain health insurance is via a group policy, through one's employer, or with health management organizations. With national attention now focused on the need for regional tertiary care for patients with complex CHD, health maintenance organizations are being held accountable for finding appropriate specialized care for ACHD patients. Patients, with their physician's support, need to be their own advocates within the health maintenance organization system and demand referrals if they believe their cardiologist is ill equipped to manage their complex cardiac care. National patient support organizations such as the Adult Congenital Heart Association have made it their mission to educate adults via newsletters, the Internet, and the like about the need for specialized cardiac care in ACHD patients with moderate to severe disease, and they provide an extensive referral network of ACHD specialists.
Currently, at least 30 states offer high-risk health insurance plans through “risk pools.” This provides a safety net for individuals who are denied health insurance because of a preexisting medical condition. More than 250 000 enrollees have been able to obtain comprehensive health insurance protection via these risk pools since the first pools were started in 1976. Risk pools are state created, are nonprofit, and usually do not require tax dollars for operational purposes. Eligible individuals must prove state residency and prove they have been rejected for similar health insurance with similar premiums by at least 1 insurer. Healthcare providers caring for ACHD patients should be aware of options available in their state. Healthcare providers need to give accurate health information to insurers in a prompt fashion so that a fair evaluation of the patient's risk status can be made.
Health and life insurance can be elusive to ACHD patients. Regardless of severity, ACHD patients face a significantly higher risk of being denied life insurance than their peers without CHD (10,40,68). Recent studies found that more than one third of ACHD patients were refused life insurance compared with 4% of age-matched peers without CHD, with no regard to severity of defect (40). A useful resource for state-by-state consumer guidelines about getting and keeping health insurance can be accessed via the Internet at www.healthinsuranceinfo.net.
1.5.7. Congenital Syndromes
Congenital syndromes, including coexisting neurological and cognitive deficits, can further complicate the psychological and social adjustment of ACHD patients. Approximately 18% of congenital heart defects are associated with a congenital syndrome or chromosomal abnormality (69). Among chromosomal abnormalities in infants with cardiovascular defects, 81% are Down syndrome, which has a CHD prevalence of 40%. Adults with Down syndrome represent a growing number of the patients seen in tertiary ACHD clinics and require careful attention to coexisting diseases and special care issues. Hypothyroidism, leukemia, Alzheimer's disease, depression, atlantoaxial subluxation, obesity, and sleep apnea are common in Down syndrome, and regular screening for these ailments should be performed. Often, sedation or general anesthesia is necessary for routine procedures, such as dental cleaning, Pap smears, or prolonged diagnostic procedures that require immobility. The risks of anesthesia and procedures need to be carefully reviewed by CHD specialists and discussed with the patient.
Approximately 15% of patients with tetralogy of Fallot and other conotruncal defects have chromosome 22q11.2 deletion, most commonly manifested as DiGeorge syndrome but also presenting as velocardiofacial (Shprintzen) syndrome and conotruncal anomaly face (Takao) syndrome (70). Patients with a history of type B interrupted aortic arch or truncus arteriosus also have a high incidence of DiGeorge syndrome. Many patients with this chromosome deletion show impairment in social function. Coexisting diseases associated with these overlapping syndromes include schizophrenia, mental disability, deafness, immune deficiencies, endocrinopathies, and clubbed foot (70).
Williams syndrome is a developmental disorder that involves connective tissue, the central nervous system, and supravalvular AS (SupraAS); it has been associated with a chromosome deletion in band 7q11.23 (70). Most Williams syndrome patients have a lack of social inhibition and some degree of mental disability that complicates planning and self-management. Adults with other syndromes, including Noonan and Turner syndromes, have varying degrees of cognitive deficits. Patients with Turner syndrome have a variety of noncardiovascular problems, including ovarian and thyroid disorders, inflammatory bowel disease, pigmented and melanotic nevi, and sensorineural deficits.
Because the cardiologist may be the only regular healthcare provider for adults who have congenital syndromes and chromosomal abnormalities in association with their CHD, careful screening and appropriate referrals (such as endocrinology, genetic counseling, psychiatry, and vocational rehabilitation) should take place. Because of the multiplicity of comorbidities and the potential for impact on cardiovascular management, there should be clarity about which healthcare provider is serving as the medical “home.” Whenever possible, the ACHD specialist should work closely with a primary physician who accepts this responsibility. Although many of these patients are dependent on others for long-term care, some are able to live independently and require sensitive counseling regarding healthcare maintenance and risks. Advice regarding sexual activity and contraception is essential, even if the patient does not request it. Genetic counseling should be offered to all patients.
1.5.8. Medical/Ethical/Legal Issues
Some ACHD patients, especially those with associated syndromes, may be incapable of providing informed consent to the degree that meets ethical and legal standards of understanding their situation, understanding the risks associated with the decision at hand, and communicating a decision based on that understanding. Adults who may require a legal surrogate to facilitate informed consent are those who are cognitively impaired, such as those with Down syndrome, and those with impaired consciousness due to severe illness. If an adult's mental competency is in question, and no appointed adult surrogate is available, a psychological evaluation should be requested (63). The issue of legal guardianship in adults with significant mental disability becomes an ethical and legal challenge when 1 or both parents die or become incapacitated by illness with no accommodation for transfer of guardianship. Guidance in addressing these issues should be included as part of the transition education and reinforced thereafter.
Advance directives can assist family members and healthcare providers in understanding a patient's wishes if they are incapable of speaking for themselves (71). All ACHD patients should be encouraged to complete an advance directive, ideally at a time during which they are not morbidly ill or hospitalized, so that they can express their wishes in a less stressful setting.
1.6. Recommendations for Infective Endocarditis
1. ACHD patients must be informed of their potential risk for IE and should be provided with the AHA information card with instructions for prophylaxis. (Level of Evidence: B)
2. When patients with ACHD present with an unexplained febrile illness and potential IE, blood cultures should be drawn before antibiotic treatment is initiated to avoid delay in diagnosis due to “culture-negative” IE. (Level of Evidence: B)
3. Transthoracic echocardiography (TTE) should be performed when the diagnosis of native-valve IE is suspected. (Level of Evidence: B)
4. Transesophageal echocardiography (TEE) is indicated if TTE windows are inadequate or equivocal, in the presence of a prosthetic valve or material or surgically constructed shunt, in the presence of complex congenital cardiovascular anatomy, or to define possible complications of endocarditis (eg, sepsis, abscess, valvular destruction or dehiscence, embolism, or hemodynamic instability). (72) (Level of Evidence: B)
5. ACHD patients with evidence of IE should have early consultation with a surgeon with experience in ACHD because of the potential for rapid deterioration and concern about possible infection of prosthetic material. (Level of Evidence: C)
1. Antibiotic prophylaxis before dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa is reasonable in patients with CHD with the highest risk for adverse outcome from IE, including those with the following indications:
a. Prosthetic cardiac valve or prosthetic material used for cardiac valve repair. (Level of Evidence: B)
b. Previous IE. (Level of Evidence: B)
c. Unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits. (Level of Evidence: B)
d. Completely repaired CHD with prosthetic materials, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure. (Level of Evidence: B)
e. Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibits endothelialization. (Level of Evidence: B)
2. It is reasonable to consider antibiotic prophylaxis against IE before vaginal delivery at the time of membrane rupture in select patients with the highest risk of adverse outcomes. This includes patients with the following indications:
a. Prosthetic cardiac valve or prosthetic material used for cardiac valve repair. (Level of Evidence: C)
b. Unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits. (Level of Evidence: C)
1. Prophylaxis against IE is not recommended for nondental procedures (such as esophagogastroduodenoscopy or colonoscopy) in the absence of active infection. (Level of Evidence: C)
The clinical setting and presentation of endocarditis have changed over the last 50 years, in part owing to technical advances (eg, cardiac surgery, hemodialysis), the use of prosthetic devices and indwelling lines, the increasing prevalence of intravenous drug abuse, the emergence of resistant organisms, and the continued development of increasingly potent antibiotics (73–78). True surgical cures of congenital cardiovascular disorders are infrequent, and almost all patients who have undergone surgery are left with some form of residua or sequelae, many of which predispose to IE (73,74,77–82).
Epidemiological studies of IE have reported underlying CHD in 11% to 13% of cases (83,84). Li and Somerville reported that IE accounted for 4% of admissions to a specialized adult congenital heart service (85). Including pediatric data, certain unoperated and operated cardiac lesions may be more susceptible to infection (Table 6). Tetralogy of Fallot, TGA, unrepaired ventricular septal defect (VSD), patent ductus arteriosus (PDA), and bicuspid aortic valves (BAVs) with aortic valve stenosis or aortic regurgitation (AR) are susceptible to IE.(73,74,79,81,86–102) Patients who have had surgical palliation of CHD (eg, systemic–to–pulmonary artery shunts) or various types of reparative surgery (often requiring prosthetic materials or valves, conduit insertion, or conduit replacement) have major predisposing conditions for IE (74,79,81,103).
The Second Natural History Study of Congenital Heart Defects reported on the incidence of IE in young adults with aortic stenosis (AS), pulmonary stenosis (PS), and VSD (104). The incidence rate was nearly 35-fold the population-based rate; viridans streptococcus was the predominant organism. The stenotic pulmonary valve was rarely affected, with only 1 case in this series. For VSDs, the risk of IE before surgical closure was more than twice that for the surgically closed VSD. In addition, the presence of AR independently increased the risk of IE in patients with VSD, whether managed medically or surgically. Of those with a surgically repaired VSD who developed IE, at least 22% were known to have a residual VSD leak.
Li and Somerville (85) reported IE in the grown-up congenital heart population comprising 185 patients (214 episodes) during 2 periods, 1983 to 1993 and 1993 to 1996, divided into unoperated or palliated (group I) and operated definitive repair or valve repair/replacement (group II). They noted no IE in atrial septal defect (ASD), closed VSD, patent ductus, isolated PS, or unrepaired Ebstein's anomaly or after Fontan-type or Mustard operations. IE in group I was most commonly represented by VSD (24%), left ventricular outflow tract (LVOT) lesions (17%), and mitral valve disorders (13%) and in group II by LVOT lesions (35%), repaired tetralogy of Fallot (19%), and atrioventricular (AV) defects (14%). Of the 185 patients, 87 (47%) had a known predisposing event (dental procedure or sepsis in group I, 33%; cardiovascular surgery in group II, 50%). Diagnosis was delayed (from onset of symptoms to time of diagnosis) in group I by 60 days and in group II by 29 days.
Niwa et al in 2005 (105) reported IE in 170 pediatric and 69 adult patients from 1997 to 2001. They noted prior cardiac surgery in 199 patients with IE, 88 of whom had surgery for cyanotic cardiovascular malformations. IE was left-sided in 46% and right-sided in 51%; the most common organisms were streptococci (50%) and staphylococci (37%). Surgery during IE was needed in 26% for large vegetations (45%) and heart failure (29%). Complications were seen in 48.5%. Mortality was 8% for medical treatment alone and 11.1% for those who also required surgery. In 33.3% of patients, conditions and procedures associated with IE were identified that preceded IE; the most common were dental manipulation (37.2%) and cardiovascular surgery (25.6%), followed by pneumonia (14.1%). Of these cases, only 28.2% had received antibiotic prophylaxis.
Di Filippo et al reported in 2006 (106) on 153 episodes of IE in CHD diagnosed with the revised Duke criteria, showing an increasing rate with 81 episodes from 1966 to 1989 (3.5 per year) and 72 episodes from 1990 to 2001 (6 per year). During the second period, there were more adults (40% later versus 9% earlier). Of interest, CHD was known in 122 patients before IE but was unrecognized in 31. Of the 153 episodes of IE, 39 occurred in patients who had repaired lesions, 35 in patients who had palliation (usually complex disease), and 79 in patients who had unoperated CHD. Tetralogy of Fallot with IE decreased from 12% to 3%, and complex cyanotic disease increased from 14% to 28%; the proportion of aortic valve anomalies and small VSDs increased. Dental procedures as a presumed cause of IE were more common during the later period (33% versus 20% earlier), cutaneous infection rose to 17% (from 5% earlier), and postoperative infection appeared less frequently later (11%) than earlier (21%). The streptococcus group continued to represent the most prevalent organisms, followed by staphylococci. Their data emphasized that current targets of prevention of IE should include complex cyanotic lesions, lesions repaired with prosthetic material, and small VSDs.
The pathogenesis of IE in part requires damaged or traumatized endothelium and a portal of entry of bacteria into the bloodstream. Bacteria may bind to platelets in the blood pool and then be deposited at the site of vascular endothelial damage. The infective lesion usually occurs at the low-pressure end of a high-gradient lesion at the site of impact of a high-velocity jet. For example, vegetations in conjunction with aortic coarctation may occur in the downstream descending aorta. With aortic valve disease, not only may vegetations occur on the ventricular surface of the valve, but the regurgitant jet impacting on the mitral valve may cause secondary vegetation. Usual sites of vegetations with a restrictive VSD occur where the high-velocity left-to-right jet impacts on the right side of the heart (ie, tricuspid valve septal leaflet or mural RV endocardium). The consequences of the infective vegetation depend on the site or structure involved and the virulence of the organism. Valvular destruction with significant valvular regurgitation or fistulous connections can cause heart failure. Endarteritis (as with patent ductus and coarctation) can cause aneurysm formation with potential for rupture. Embolization of vegetative material can cause arterial obstruction (eg, stroke) and possible abscess formation, and right-sided embolization to the lung can mimic pneumonia. Immunologic reactions can trigger glomerulonephritis or vasculitis as a result of the deposition of circulating immune complexes in the small vessels in skin (Janeway lesion and Osler node) (75).
Many cases of clinically suspected IE are difficult to diagnose with certainty because of altered immune response, prior antibiotic exposure, or indolent organisms and in some patients with acute right-sided IE in whom the systemic and immune responses have not developed (73,75,76,80,81). Now widely accepted, Durack et al incorporated 2-dimensional echocardiography as a means of demonstration of vegetations (77,107). The Duke criteria defined 2 major criteria (positive blood culture with typical microorganisms and evidence of endocardial involvement, eg, a typical vegetation on an echocardiogram) and 6 minor criteria (ie, predisposition, fever, vascular phenomena, immunologic phenomena, suggestive microbiological evidence, and echocardiographic findings consistent with endocarditis but not meeting major echocardiographic criteria), with categories defined as definite, possible, and rejected (107). Echocardiography is crucial in the diagnosis of IE. In general, a TTE study is useful in confirming the presence of vegetation, but often, the sensitivity is too low to rule out its absence. If a TTE study is equivocal, or in the presence of a prosthetic valve or complex congenital cardiovascular anatomy in which transthoracic windows may be inadequate, TEE is indicated (73 to 79, 81, 108 to 112). TEE is particularly important in the search for IE in the adolescent and adult for evaluation of the thoracic aorta, ventricular outflow tracts, and valved conduits and for visualization of the entire ventricular septum. Given the complexity of many of the malformations and the wide array of surgical palliations and repairs, however, performance and interpretation of echocardiography must be done by those with expertise in the native and altered postoperative (109) anatomy (103,108,110–112).
A delay in diagnosis of IE carries the risk of significant morbidity and mortality. A high index of suspicion for IE in any patient with operated or unoperated CHD is a key to early diagnosis (74,78,79,81,103,113–115). Cardiac lesions and their relative risk of developing IE are listed in Table 7.
An antecedent event is identified in a minority of cases with IE (74,79). Awadallah et al identified predisposing events in 56%, with unprotected dental work, recent open heart surgery, and skin infections being the most common (116). Gersony et al found that an antecedent event could be identified in 32% of cases; these events included dental work, previous bacterial infection (ie, pharyngitis, sinusitis, enteritis, or pelvic inflammatory disease), and cardiac catheterization (101).
Additional issues more specific for patients with CHD and risk for IE may not be well recognized by many practitioners (72,74,78–80). Patients with unoperated cyanotic heart disease frequently have acne or have spongy, friable gums; appropriate care is necessary to diminish the risk of bacteremia. Epistaxis and hemoptysis are frequent in the cyanotic patient; nasal cautery may be a risk factor for IE. Nail biting is a problem, with the possibility of local infection being a focus for bacteremia. High-risk behaviors (eg, intravenous drug abuse, body piercing, or tattoos) not uncommon in adolescents and young adults in particular are well-known risk factors, especially for acute staphylococcal IE on the right side of the heart, and the patient should be informed of the risks of these activities. The use of intrauterine devices for female contraception is somewhat controversial because of concern about endocarditis, although the rate of infection is only approximately 1.4 times normal, provided that sexual relationships are monogamous. The AHA recommendations do not advise antibiotic prophylaxis for patients before genitourinary procedures, but because of the high risk for adverse outcome in patients with prosthetic cardiac valves and those with cyanotic CHD and the potential for infection in the setting of a complex vaginal delivery, this committee proposed that antibiotics might be considered in those high-risk patients at the time of membrane rupture (recognizing that proof of efficacy of prophylaxis is not available) (117).
In all cases of IE, cultures should be obtained to try to establish the causative organism before antibiotics are initiated (73,75,78,82,112). CHD patients who present with fever and potential IE should have blood cultures drawn before antibiotic therapy is initiated to avoid subsequent false-negative blood cultures (78,103,118). Recognizing that initial therapy is usually parenteral and usually intravenous, one should recall that cyanotic patients with right-to-left shunts have the possibility of “paradoxical” systemic embolization and, as such, risk of stroke. Air filters should be used on the line with meticulous attention to avoiding injection of air bubbles. Details of all aspects of medical and antimicrobial management of IE are beyond the scope of this review and are addressed by a separate AHA working group, as well as other authors (78,81,99,119,120). Collaboration with an infectious disease specialist is invaluable. Prompt referral of the adult patient with CHD to a specialized center is usually indicated because hemodynamic deterioration may be rapid, and surgical treatment of often complicated anatomy and/or reoperation may be required (78,82). Early consultation with a cardiac surgeon with experience treating adults with CHD is appropriate. Surgical intervention is considered in patients with uncontrolled congestive heart failure, continued emboli, medically uncontrolled infection, prosthetic material infection, and development of heart block (73,75,78,80,112–114,121). Management decisions regarding infected prosthetic valves or conduits in which the duration of preoperative antibiotic therapy must be balanced against the risk of reoperation must be made in collaboration with the surgeon. Ultimately, to reduce costs without risking efficacy, prolonged home parenteral antibiotics may be required after the initial inpatient hospitalization.
Prevention of IE includes nonchemotherapeutic and chemotherapeutic methods (74,75,78,80,81,103). Clinical judgment and discretion are required. It is always worthwhile to strive to provide evidence-based medical care. However, the Cochrane Collaboration did not provide evidence proving whether or not penicillin prophylaxis is effective protection against bacterial endocarditis in those with lesions considered at risk for development of IE and who were about to undergo an invasive dental procedure. They also noted that there is lack of evidence to support published guidelines in this area or to show whether the potential harm or cost of penicillin outweighs the benefit (122).
On the basis of a “revised” assessment regarding the risk of bacteremia-induced endocarditis, new guidelines for the prevention of endocarditis were published in 2006 by the Working Party of the British Society for Antimicrobial Chemotherapy (123). The 2006 guidelines recommend that antimicrobial prophylaxis for dental procedures be confined to those with (1) previous IE, (2) prosthetic cardiac valves, or (3) surgically constructed pulmonary shunts or conduits. In contrast, for bacteremic nondental procedures, the 2006 group expanded the “dental risk” list to also include (4) complex CHD (except not secundum ASD, which is presumably isolated and uncomplicated), (5) complex LVOT obstruction, including AS and BAVs, (6) acquired valvulopathy, and (7) mitral valve prolapse in the presence of echocardiographic “substantial leaflet pathology and regurgitation.” The British Society for Antimicrobial Chemotherapy justifies its decisions by shifting the emphasis from “procedure-related bacteremia” to “cumulative bacteremia.”
The 2007 AHA guidelines for the prevention of endocarditis have substantially changed the recommendations for antibiotic prophylaxis on the basis of a consensus of expert opinions (72). The new, simplified recommendations are based on the proposition that most bacteremia occurs during activities of daily living, that IE is more likely to result from long-term cumulative exposure to these daily random bacteremias than from procedural bacteremias, and that proof is lacking that prophylaxis prevents any (or at most a very small number) cases of IE. They posit that the risks of antibiotic adverse events in the patient (allergic reactions) and the emergence of resistant organisms exceed any proven benefit of antibiotic prophylaxis against IE.
The new AHA guidelines appropriately emphasize maintenance of oral health and hygiene to reduce daily bacteremia and underscore that this is more important than any dental antibiotic prophylaxis. Accordingly, the 2007 AHA writing committee for the updated guidelines on prevention of endocarditis concluded that antibiotic prophylaxis for dental procedures likely to induce procedural bacteremia (those that involve manipulation of gingival tissue or the periapical region of the teeth or perforation of the gingival mucosa) should be confined to cardiac conditions associated with the most significant adverse outcomes should IE develop (72). They included in this group those with previous IE; those with prosthetic cardiac valves or surgically constructed conduits or shunts; those with unrepaired cyanotic CHD or CHD repaired with prosthetic material or devices (until 6 months after the procedure); those with repaired CHD with residual defects at or adjacent to the site of a prosthetic patch or device; and cardiac transplant patients who develop valvulopathy. They specifically recommend no IE prophylaxis before gastrointestinal or genitourinary procedures, a major departure from previous guidelines. The new AHA guidelines have engendered some considerable controversy and may violate long-standing patient and provider expectations and practice. Concern has been expressed that changes in preexisting recommendations were not based on new data or randomized trials and that absence of proof of efficacy and safety cannot be used as proof of absence of efficacy and safety of antimicrobial prophylaxis (124). The present ACHD Guideline Committee understands that there may be reluctance to deviate from prior recommendations for patients with some forms of CHD. This reluctance may be especially true for patients with BAV or coarctation of the aorta. In select circumstances, the committee understands that some clinicians and some patients may still feel more comfortable continuing with IE prophylaxis. Accordingly, this committee recommends that healthcare providers discuss the rationale for these new changes with their patients, including the lack of scientific evidence demonstrating proven benefit for IE prophylaxis. 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 growing acceptance of the new guidelines among both provider and patient communities.
This ACHD writing committee proposes that the “high-risk” group in whom it is reasonable to give antibiotic prophylaxis before dental procedures would include the following: (1) those with a prosthetic cardiac valve; (2) those with prior IE; (3) those with unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits; (4) those with repaired CHD with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure; and (5) those with repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibit endothelialization.
We emphasize that nonchemotherapeutic methods are particularly important in the adolescent or young adult patient with CHD, among whom nail biting, acne, and problems with dental health are common. Oral prevention starts with meticulous oral care and routine preventive care by a dentist or oral hygienist. A patient with cyanotic heart disease often has spongy, friable gums, and a soft-bristle toothbrush must be used. Female contraception should be planned with the risks and benefits of intrauterine devices kept in mind.
The patient's knowledge of the need for and the type of IE prophylaxis is also an important issue (77,103,125). Caldwell et al noted that fewer than 50% of families knew about endocarditis prevention or precautions, and even fewer understood why prophylaxis was considered indicated (91). Cetta and Warnes reported in 1995 from their specialized ACHD clinic that those with CHD had inadequate knowledge about their cardiac lesion, about IE, and about prophylaxis (125). With aggressive education in their clinic, patient knowledge improved, but they emphasized that educational efforts need to be reinforced regularly. A patient should be given a detailed explanation of his or her diagnosis and the rationale for IE prevention, and the patient's specific regimen for dental procedures should be provided. Information about the signs and symptoms of IE should also be provided. At every subsequent visit, it should again be verified that the patient knows what is required for dental care and prophylaxis (74).
1.7. Recommendations for Noncardiac Surgery
1. Basic preoperative assessment for ACHD patients should include systemic arterial oximetry, an ECG, chest x-ray, TTE, and blood tests for full blood count and coagulation screen. (Level of Evidence: C)
2. It is recommended that when possible, the preoperative evaluation and surgery for ACHD patients be performed in a regional center specializing in congenital cardiology, with experienced surgeons and cardiac anesthesiologists. (Level of Evidence: C)
3. Certain high-risk patient populations should be managed at centers for the care of ACHD patients under all circumstances, unless the operative intervention is an absolute emergency. High-risk categories include patients with the following:
a. Prior Fontan procedure. (Level of Evidence: C)
b. Severe pulmonary arterial hypertension (PAH). (Level of Evidence: C)
c. Cyanotic CHD. (Level of Evidence: C)
d. Complex CHD with residua such as heart failure, valve disease, or the need for anticoagulation. (Level of Evidence: C)
e. Patients with CHD and malignant arrhythmias. (Level of Evidence: C)
4. Consultation with ACHD experts regarding the assessment of risk is recommended for patients with CHD who will undergo noncardiac surgery. (Level of Evidence: C)
5. Consultation with a cardiac anesthesiologist is recommended for moderate- and high-risk patients. (Level of Evidence: C)
Performance of any surgical procedure in ACHD patients carries a greater risk than in the normal population. Certain surgical procedures are frequently required in cyanotic patients, such as intervention for gallstones, scoliosis, and, less commonly, cerebral abscess. The risk for noncardiac surgery depends on the nature of the underlying CHD, the extent of the procedure, and the urgency of intervention. Table 7 lists lesions at moderate and high risk for noncardiac surgery.
A thorough evaluation of the patient with CHD should be undertaken before anticipated noncardiac surgery. Basic preoperative assessment includes an ECG, chest x-ray, TTE, and blood tests for full blood count and coagulation screen. It is recommended, when possible, that the preoperative evaluation and surgery be performed in an ACHD center by experienced surgeons and cardiac anesthesiologists. This allows close perioperative follow-up by an ACHD specialist. The specialist team should always be involved in the care of the complex and cyanotic adult patient with CHD, because this minimizes avoidable errors that can cause important morbidity or even death (126).
Select high-risk patient populations should be managed at centers for the care of ACHD patients under all circumstances, unless the operative intervention is an absolute emergency. These patients include those with prior Fontan procedure, severe PAH, cyanotic CHD, or complex CHD with residua such as heart failure, valve disease, or the need for anticoagulation.
Patients with cyanotic CHD, especially when associated with PAH, are at highest risk from noncardiac surgery (126). The bleeding risk can be reduced by preoperative phlebotomy if the hematocrit is more than 65% (127). Anesthetic management is critical, because a fall in systemic vascular resistance can worsen hypoxia, resulting in hemodynamic collapse. Long operations associated with hemodynamic instability and that require large-volume fluid replacement are associated with increased perioperative mortality. Fluid balance is critical in cyanotic and single-ventricle patients and those with heart failure because of occult renal failure in these patients.
Postoperatively, patients with CHD may need intensive care unit monitoring facilities even for relatively minor procedures. Nursing staff should be informed about the specific issues related to the CHD. Special issues that should be considered include administration of endocarditis prophylaxis, the need for anticoagulation around the time of the procedure, anticipation of special problems related to the underlying hemodynamics, filters for intravenous lines in cyanotic patients, prevention of venous thrombosis, monitoring of renal function, special care with drug administration, and the reduced arm blood pressure measurement in patients with prior classic Blalock-Taussig shunts. There is no evidence that cyanotic heart disease per se leads to liver disease (refer to Section 10, Tetralogy of Fallot, and Section 14, Tricuspid Atresia/Single Ventricle, for information regarding long-standing central venous hypertension leading to cardiac cirrhosis). There is increased prevalence of hepatitis C infection in adult patients who underwent CHD surgery before screening in 1992, and therefore these patients should be screened (128).
1.8. Recommendations for Pregnancy and Contraception
1. Patients with CHD should have consultation with an ACHD expert before they plan to become pregnant to develop a plan for management of labor and the postpartum period that includes consideration of the appropriate response to potential complications. This care plan should be made available to all providers. (Level of Evidence: C)
2. Patients with intracardiac right-to-left shunting should have fastidious care of intravenous lines to avoid paradoxical air embolus. (Level of Evidence: C)
3. Prepregnancy counseling is recommended for women receiving chronic anticoagulation with warfarin to enable them to make an informed decision about maternal and fetal risks. (129–131) (Level of Evidence: B)
1. Meticulous prophylaxis for deep venous thrombosis, including early ambulation and compression stockings, can be useful for all patients with intracardiac right-to-left shunt. Subcutaneous heparin or low-molecular-weight heparin is reasonable for prolonged bed rest. Full anticoagulation can be useful for the high-risk patient. (Level of Evidence: C)
1. The estrogen-containing oral contraceptive pill is not recommended for ACHD patients at risk of thromboembolism, such as those with cyanosis related to an intracardiac shunt, severe PAH, or Fontan repair. (Level of Evidence: C)
Congenital malformations now represent the most common cause of maternal morbidity and mortality from heart disease in North America. Better assessment and management of this group of patients is likely to make a substantial improvement in outcomes for mother and baby (132).
Both men and women with ACHD should have a thorough understanding of the risks of transmitting CHD to their offspring. Counseling by an ACHD expert before pregnancy is important and should include genetic evaluation and, specifically for women, assessment of potential fetal risk, risk of prematurity or low birth weight in the offspring, review of medications that may be deleterious to the fetus, appropriate management of anticoagulation, and discussion of potential maternal complications (132). If pregnancy occurs, fetal echocardiography should be obtained and its consequences discussed (132).
The outcome of pregnancy is favorable in most women with CHD provided that functional class and systemic ventricular function are good. PAH presents a serious risk during pregnancy, particularly when the pulmonary pressure exceeds 70% of systemic pressure, irrespective of functional class. Events often occur after delivery (133). The need for full anticoagulation during pregnancy, although not a contraindication, poses an increased risk to both mother and fetus (134). The relative risks and benefits of the different anticoagulant approaches need to be discussed fully with the prospective mother. There is a small group of patients with complex CHD or high-risk disorders in whom pregnancy is either dangerous or contraindicated owing to the risk to mother or fetus. If pregnancy occurs and continues with any of these disorders, these high-risk patients should be managed and delivered in specialized centers with multidisciplinary expertise and experience in CHD, obstetrics, anesthesiology, and neonatology. A coordinated care pathway for supervision of delivery and the postpartum period needs to be developed and in place by the third trimester and made available to all caregivers and to the patient. A normal vaginal delivery or an assisted delivery is usually feasible and may be preferable for patients with CHD. Cesarean delivery is recommended in patients with CHD for obstetric reasons and for women fully anticoagulated with warfarin at the time of delivery due to the risk of fetal intracranial hemorrhage.
Medications should be used only when necessary in any pregnant patient. Certain medications are contraindicated during pregnancy; these medications include angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers. These medications cause congenital and renal disorders in the fetus when given during pregnancy; therefore, they should be discontinued before pregnancy occurs or early during pregnancy if possible (135). Warfarin should be used only after full discussion with the patient about the risks of using warfarin during pregnancy (136).
Although endocarditis is a recognized risk for maternal morbidity and mortality, endocarditis prophylaxis around the time of delivery is not universally recommended for patients with structural heart disease, because some believe that the risk of bacteremia is low. Others routinely administer antibiotics because it is not known in advance whether or not instrumentation will be required. Thus, there is no consensus on this point (117). Antibiotics should be considered for those at highest risk of an adverse outcome and, when appropriate, given as the membranes rupture. Intravenous amoxicillin and gentamicin should be considered for women with high-risk anatomy or previous history of endocarditis (see Section 1.6, Recommendations for Infective Endocarditis).
It is the duty of the ACHD specialist to provide or otherwise make available informed advice on contraception, including discussion of risks. There are limited data on the safety of various contraceptive techniques in ACHD patients. The estrogen-containing oral contraceptive pill is generally not recommended in ACHD patients at risk of thromboembolism, such as those with cyanosis, prior Fontan procedure, atrial fibrillation, or PAH. In addition, this form of contraceptive therapy may upset anticoagulation control. However, medroxyprogesterone, the progesterone-only pills, and levonorgestrel may also cause fluid retention and should be used with caution in patients with heart failure. Depression and breakthrough bleeding may prevent the use of the progesterone-only pills, and there is a higher failure rate than with combined oral contraceptives.
Levonorgestrel, barrier methods, or tubal ligation are the recommended contraceptive methods for women with cyanotic CHD and PAH. The potential complications of the “morning after pill” (levonorgestrel “plan B”) should be explained to those at risk of acute fluid retention. Tubal ligation, although the most secure method of contraception, can be a high-risk procedure in patients with complex CHD or those with PAH. Hysteroscopic sterilization (Essure) may be reasonable for high-risk patients (137). Sterilization of a male partner of a woman with CHD should only occur after full explanation of the prognosis to the patient. The specialist in the ACHD clinic needs to interact with both the general practitioner and the gynecologist to provide optimal advice regarding contraception. The risk of endocarditis with intrauterine devices in women with CHD is controversial, and recommendations should be individualized on the basis of discussions between the cardiologist and gynecologist.
Breast-feeding is safe in women with CHD. Women requiring cardiovascular medications should be aware that many of the medications will cross into breast milk and should clarify the potential effect of medications on the infant with a pediatrician.
1.9. Recommendations for Arrhythmia Diagnosis and Management
1. Complete and appropriate noninvasive testing, as well as clear knowledge of the specific anatomy and review of all surgical and procedural records, is recommended before electrophysiological testing or device placement is attempted in ACHD patients. (Level of Evidence: C)
2. Decisions regarding tachycardia management in ACHD patients should take into account the broad cardiovascular picture, particularly repairable hemodynamic issues that might favor a surgical or catheter-based approach to treatment. (Level of Evidence: B)
3. Catheter ablation procedures for ACHD patients should be performed at centers where the staff is experienced with the complex anatomy and distinctive arrhythmia substrates encountered in congenital heart defects. (Level of Evidence: B)
4. Pacemaker and device lead placement (or replacement) in ACHD patients should be performed at centers where the staff is familiar with the unusual anatomy of congenital heart defects and their surgical repair. (Level of Evidence: B)
5. Epicardial pacemaker and device lead placement should be performed in all cyanotic patients with intracardiac shunts who require devices. (Level of Evidence: B)
1. It is reasonable to recommend the use of an implantable cardioverter defibrillator for any patient who has had a cardiac arrest or experienced an episode of hemodynamically significant or sustained ventricular tachycardia (VT). (Level of Evidence: C)
2. Pacemaker implantation can be beneficial in ACHD patients with bradyarrhythmias and may be helpful in overdrive pacing in patients with difficult-to-control tachyarrhythmias (see ACC/AHA/HRS 2008 Guidelines for Device-Based therapy of Cardiac Rhythm Abnormalities). (138) (Level of Evidence: B)
1. Pacemaker implantation may be beneficial for asymptomatic adult patients with resting heart rates of less than 40 beats per minute or abrupt pauses in excess of 3 seconds. (Level of Evidence: C)
Cardiac arrhythmias are a major source of morbidity and mortality for ACHD patients. Although rhythm disorders can often be observed in adults with unrepaired or palliated defects, the most difficult cases usually involve patients who have undergone prior intracardiac repairs, especially when this reparative surgery was performed relatively late in life (139,140). In this setting, the electrical pathology stems from the unique and complex myocardial substrates created by septal patches and suture lines in combination with cyanosis and abnormal pressure/volume status of variable duration. Virtually the entire spectrum of rhythm disturbances is manifested in these patients, including some disorders that are specific to the anatomic defect or the surgical technique used for repair (Table 8).
The optimal management strategy for many of these arrhythmias is as yet undetermined. The dramatic evolution of interventional electrophysiology in recent years, including techniques such as catheter or surgical ablation and implantation of antitachycardia devices, has broadened the list of therapeutic options significantly, but much of the literature in this field is still limited to small institutional series and anecdotal case reports. In the absence of large prospective outcome trials, current policies for arrhythmia treatment often involve extrapolation from studies of more conventional types of adult heart disease, such as ischemic myopathy. This approach, although a useful starting point, can underestimate the unique anatomic and physiological challenges of the ACHD patient. More organized multicenter research is needed in this area, as is more aggressive cross-training of electrophysiologists from both pediatrics and internal medicine to meet the special needs of these patients. Furthermore, until knowledge of these conditions is more widely disseminated, it is reasonable to recommend that interventional arrhythmia procedures be performed at centers where the staff is experienced with the complex anatomy and distinctive arrhythmia substrates encountered in congenital heart defects.
1.9.1. Management of Tachyarrhythmias: Wolff-Parkinson-White Syndrome
Accessory pathways can complicate certain forms of CHD, especially Ebstein's anomaly of the tricuspid valve (141). Tachycardia symptoms may begin in childhood but become increasingly problematic in adult years, when atrial dilation or surgical scars predispose the patient to atrial flutter or atrial fibrillation with potential for rapid conduction over an accessory pathway. An attempt at definitive therapy with catheter ablation has become the standard of care for these patients. However, compared with simple accessory pathway ablation in a structurally normal heart, the acute success rates are reported to be lower and the risk of recurrence higher in patients with anatomic defects (141–143). These differences appear to relate to the challenges of distorted anatomic landmarks, abnormal location for the AV node, and a high incidence of multiple pathways in the CHD population. Intraoperative accessory pathway ablation can be considered in the patient with Ebstein's anomaly referred for operative intervention for tricuspid valve disease. This approach has been demonstrated to be safe and effective (144).
1.9.2. Intra-Atrial Reentrant Tachycardia or Atrial Flutter
The most common form of tachycardia seen in the ACHD patient population is macroreentry within atrial muscle. This arrhythmia usually surfaces as a late postoperative disorder, and in children, it has been associated with chronotropic incompetence. Although it may arise after nearly any procedure that involves a right atriotomy (even simple closure of an ASD), the incidence is clearly highest after the Mustard, Senning, and Fontan operations, in which as many as 30% to 50% of patients can be expected to develop a symptomatic episode during extended follow-up (144,145). The term “intra-atrial reentrant tachycardia” (IART) has become the customary designation for this arrhythmia to distinguish it from classic atrial flutter seen in structurally normal hearts (146–148). Whereas typical atrial flutter involves a very predictable circuit around the tricuspid annulus that results in the familiar ECG appearance of sawtooth flutter waves at a rate of 300 beats per minute, IART can involve novel circuits around surgical scars and patches that generate a much wider spectrum of atrial rates and P-wave contours. Generally, IART tends to be slower than typical flutter, with atrial rates in the range of 170 to 250 beats per minute (144). In the setting of a healthy AV node, these rates will frequently allow a pattern of 1:1 AV conduction that may result in hemodynamic instability, syncope, or possibly death (149–151). Even if the ventricular response rate is safely titrated, sustained IART of long duration can be responsible for thromboembolic events.
Once IART is recognized, acute interruption is easily accomplished with either electrical cardioversion, overdrive pacing (150), or administration of certain class I or class III antiarrhythmic drugs (152). The far more difficult challenge is prevention of recurrence and adequate assessment of hemodynamic status that might predispose to recurrent tachycardia. Chronic antiarrhythmic drugs are still used in many cases, but the general experience with pharmacological therapy for this condition has been discouraging (149,153), which has led to a growing preference for nonpharmacological options at most centers.
Pacemaker implantation can be useful for those patients who have concomitant sinus node dysfunction as a prominent component of their clinical picture. Simply increasing the atrial rate to an appropriate level for the hemodynamic status can often result in marked reduction in IART frequency (150), while at the same time making it safer to prescribe medications that might aggravate bradycardia (138). Pacemakers with advanced programming features that incorporate atrial tachycardia detection and automatic burst pacing may also be beneficial in select cases (150,155) but carry the risk of accelerating the atrial rate and must thus be used cautiously in patients with robust AV conduction. Newer-generation implantable cardioverter defibrillators equipped with algorithms for both atrial tachycardia and VT detection and treatment, including atrial antitachycardia pacing and low-energy shocks for atrial tachycardia, have also been used successfully in a small number of ACHD patients with recurrent IART.
Catheter ablation has been adopted by many institutions as an early intervention for recurrent IART. The technique has evolved rapidly in terms of mapping accuracy and effectiveness, particularly since the introduction of 3-dimensional mapping technology for improved circuit localization (156,157) and irrigated-tip or large-tip ablation catheters for more effective lesion creation (158). With current technology, acute success rates of nearly 90% can be achieved with catheter ablation, although later tachycardia recurrence is still disappointingly common (159). The recurrence risk appears to be particularly high in the Fontan population of patients, who tend to have multiple IART circuits and the thickest/largest atrial dimensions. Although still far from perfect, ablation results for IART are likely to improve with continued advances in technology and even now are superior to the degree of control obtained with medications alone.
If the above measures fail to prevent IART recurrence, or if a patient with IART is returning to the operating room for hemodynamic reasons, consideration should be given to surgical ablation during a right atrial Maze operation. This procedure is used most commonly for the Fontan population with the most refractory variety of IART and is usually combined with revision of the Fontan connection or conversion from an older atriopulmonary anastomosis to a cavopulmonary connection. Results are encouraging, with very low rates of IART recurrence (160), but the surgical risks must be weighed against the electrophysiological benefit.
1.9.3. Atrial Fibrillation
Although far less common than IART in ACHD patients, atrial fibrillation is no less difficult to treat. It occurs most often in patients with congenital AS, mitral valve disease, or palliated single ventricles (161). Management principles are similar to atrial fibrillation encountered in other forms of heart disease, beginning with medical therapy for anticoagulation and ventricular rate control as needed, followed by electrical cardioversion. Class III antiarrhythmic agents may offer protection against recurrence of atrial fibrillation for some patients, but as in the case of IART, drug therapy has been only marginally successful for this group. Also similar to IART, pacemaker implantation may reduce atrial fibrillation episodes in patients with concomitant sinus node dysfunction. Successful elimination of atrial fibrillation has also been reported after combined right and left atrial Maze operations, which may be reasonable to consider if a patient requires cardiac surgery to address hemodynamic issues. Catheter ablation has not yet been extended in any systematic way to atrial fibrillation in the ACHD patient population.
1.9.4. Ventricular Tachycardia
There are several scenarios in which high-grade ventricular arrhythmias may develop in the ACHD patient. The most familiar involves macroreentrant VT as a late complication in postoperative patients who have undergone ventriculotomy and/or patching of a VSD, such as tetralogy of Fallot repair. In such cases, the reentry circuit is typically caused by narrow conduction corridors around regions of scar in the RV outflow tract (RVOT). The incidence of late VT or sudden death for repaired tetralogy has been estimated between 0.5% and 6.0% in various series (140,162,163). Some patients with slow organized VT may be hemodynamically stable at presentation, but VT tends to be rapid for the majority, producing syncope or cardiac arrest as the presenting symptom. The clinical picture is often confounded by the fact that symptomatic atrial tachycardias are also common in ACHD patients (164), which makes it difficult at times to tell whether an event was caused by VT, IART, or both.
Predicting which CHD patients will develop VT in advance of an episode remains a challenge. Studies seeking risk factors in the population with tetralogy of Fallot have identified older age at time of reparative surgery, advanced degrees of RV dilation, and prolonged QRS duration greater than 180 milliseconds as independent variables (140,165–167), although the predictive accuracy for each of these factors is imperfect. Holter monitoring and exercise testing have also been examined as screening tools with some degree of correlation between spontaneous ectopy and future VT events, but because ectopy on ambulatory monitoring is nearly ubiquitous in this population, the positive predictive value is diluted. Formal ventricular stimulation study can discriminate between high- and low-risk CHD patients (168,169) but remains too imperfect and too impractical to be recommended as a general screening tool. Intracardiac electrophysiology testing is usually reserved for selected patients with concerning symptoms or Holter findings when VT is suspected but not yet proven. At present, there is no generally accepted scheme for rhythm surveillance in asymptomatic patients with tetralogy of Fallot. Some combination of the above tests must be viewed in the context of the individual patient's history and general hemodynamic status to guide testing and treatment decisions whenever symptoms are minimal or absent. Symptoms of palpitations, dizziness, or unexplained syncope would obviously heighten the index of suspicion and should trigger a thorough and prompt diagnostic evaluation, which probably should include formal electrophysiological testing.
Although tetralogy of Fallot is typically cited as the archetypal lesion when VT in the ACHD patient population is discussed, serious ventricular arrhythmias may also develop in a number of other malformations, even in the absence of direct surgical scarring to ventricular muscle. Examples include congenital AS, dextro- or levo-TGA when the right ventricle supports the systemic circulation, severe Ebstein's anomaly, certain forms of single ventricle, and VSD with PAH. The appearance of ventricular arrhythmias in these cases commonly coincides with deterioration in overall hemodynamic status (165).
Therapy for VT in ACHD patients is complex and evolving. Similar to VT treatment in ischemic heart disease, sole reliance on pharmacological management has now been largely abandoned. Empirical beta blockade and class I or class III agents might still be prescribed in rare cases when the clinician remains ambivalent about a patient's VT risk after thorough testing, but no data support this approach once sustained VT or cardiac arrest has occurred. Drug therapy has now been replaced at most centers by more definitive interventions, such as implantable cardioverter defibrillator placement, catheter ablation, or arrhythmia surgery. Before deciding among these options, hemodynamic catheterization combined with comprehensive electrophysiology study should be obtained. Reparable hemodynamic issues may be identified that would favor a surgical strategy for therapy, such as closure of a residual septal defect or relief of valve regurgitation, combined with intraoperative VT mapping and ablation (170). In addition, IART may be identified as either a contributing or confounding factor for a patient's symptoms and can be addressed with either catheter or surgical ablation at the same setting. Finally, if VT can be induced that is slow enough to support the circulation during mapping, catheter ablation of the VT circuit may be considered on the basis of the risks and benefits to the individual patient (171,172). Although reports of ablation for VT in ACHD patients are still limited to small series, it appears that it can be accomplished with a reasonable degree of acute success (173,174); however, the risk of VT recurrence after ablation is now being more clearly defined and may exceed 20% (174). It seems wise to reserve ablation as isolated VT therapy for those CHD patients with superior hemodynamics and single circuits of slow tachycardia, and even then, to perform follow-up stimulation studies to ensure that the same or different circuits cannot be induced before dismissing the need for an implantable cardioverter defibrillator. Perhaps a more important role for catheter ablation may be as supplemental therapy to reduce the shock burden in patients with frequent VT recurrences who already have an implantable cardioverter defibrillator in place.
Most ACHD patients with documented or highly suspected VT are now managed with an implantable cardioverter defibrillator (175). Transvenous systems are possible in most cases, with the notable exceptions of single-ventricle patients, those with obstructed venous channels, and those with significant intracardiac shunts who would be at risk for systemic embolic events from an intravascular lead. Acute defibrillation thresholds in CHD patients are comparable to those encountered in acquired heart disease. What may differ during follow-up is the need for lead revision. There is now growing evidence that lead failure from insulation or conductor breaks is relatively high in this group (175), which possibly reflects a more active lifestyle for young ACHD patients than for an older population with ischemic disease.
1.10. Management of Bradycardias
1.10.1. Sinoatrial Node Dysfunction
Although some rare forms of heterotaxy syndrome can be associated with congenital dysfunction or absence of the sinoatrial node, pathological sinus bradycardia in ACHD patients is more often an acquired problem related to cardiac surgery. Direct trauma to the sinoatrial node or its arterial supply occurs fairly frequently after the Mustard, Senning, Glenn, and Fontan operations (139,144,176,177). The likelihood of a patient developing IART or atrial fibrillation becomes significantly increased in this setting. Furthermore, patients with suboptimal hemodynamics may become symptomatic owing to chronotropic incompetence and the loss of AV synchrony. The updated guidelines for antibradycardia pacemaker implantation developed by the ACC and AHA (138) include information pertinent to CHD under the heading of “children and adolescents.” These same guidelines can be applied reasonably well to ACHD patients. Implantation of an atrial or dual-chamber pacing system with activity responsiveness is recommended as a Class I indication in any symptomatic patient with sinoatrial node dysfunction. This will include most of those with tachy-brady syndrome and symptoms from recurrent atrial tachycardias, as well as any patient who is shown to have pause-dependent VT. Pacemaker implantation is also recommended as a Class IIb indication for asymptomatic adult patients with resting heart rates of less than 40 beats per minute or abrupt pauses in excess of 3 seconds. The possibility of developing ventricular dysfunction with apical ventricular pacing exists. Although dual-chamber pacing systems may be implanted, manipulation of pacing programming to maintain atrial pacing with intact AV conduction is desirable.
There are a number of unique technical considerations during pacemaker implantation in ACHD patients. Transvenous lead positions, for example, will often have to be modified in response to the cardiac lesion and vascular redirection imposed by surgical patches or anastomotic stenosis, as occurs after the Mustard or Senning operations. Transvenous leads may be impossible or ill advised in other CHD lesions, including in some postoperative Fontan patients or patients with intracardiac shunting, thereby necessitating epicardial lead placement. With either the endocardial or epicardial approach, it can be challenging to locate lead anchor points with proper pacing and sensing function due to fibrosis and patching, particularly for an atrial lead. Clear knowledge of the specific anatomy and review of all surgical records are essential before device placement is attempted in these patients.
1.10.2. Atrioventricular Block
Surgical repair of CHD may result in direct trauma to the AV conduction tissues. Although improved knowledge of the anatomy of the AV node and His bundle in various CHD lesions has lessened its occurrence (178), closure of some VSDs, surgery for left-sided heart outflow obstruction, and replacement or repair of an AV valve may still be complicated by AV block. Fortunately, in more than half of cases, this injury is a transient phenomenon, and conduction recovers within 7 to 10 days of the operation (179). Permanent pacemaker implantation is advised (138) as a Class I indication for any patient with postoperative advanced second- or third-degree AV block that is not expected to resolve or persists at least 7 to 10 days after cardiac surgery. A pacemaker is also recommended by some as a Class IIb indication when surgical AV block recovers but the patient is left with permanent bifascicular block.
The AV conduction tissues may also be congenitally abnormal in terms of their location and function in specific forms of CHD, notably congenitally corrected TGA (CCTGA), as well as AV septal defect (AVSD), particularly those with Down syndrome (180–182). These patients may be more susceptible to surgical or catheter-induced AV block but may also develop AV block spontaneously at any point in time ranging from fetal life to adulthood. Patients with these particular anatomic defects merit periodic assessment of AV conduction with serial ECGs and Holter monitoring, even if AV conduction was not directly affected by surgery.
1.11. Cyanotic Congenital Heart Disease
Right-to-left intracardiac or extracardiac shunts result in hypoxemia, erythrocytosis, and cyanosis. Cyanotic ACHD patients should be seen at least annually by an ACHD specialist. Survival is determined by the type of underlying CHD and the medical complications of cyanosis.
1.11.1. Recommendations for Hematologic Problems
1. Indications for therapeutic phlebotomy are hemoglobin greater than 20 g per dL and hematocrit greater than 65%, associated with headache, increasing fatigue, or other symptoms of hyperviscosity in the absence of dehydration or anemia. (Level of Evidence: C)
1. Repeated routine phlebotomies are not recommended because of the risk of iron depletion, decreased oxygen-carrying capacity, and stroke. (Level of Evidence: C)
Cyanosis in patients with CHD has profound hematologic consequences that may affect many organ systems and need to be recognized and managed appropriately. The hematologic complications of chronic hypoxemia are erythrocytosis, iron deficiency, and bleeding diathesis (183). The increase in red blood cell mass that accompanies cyanosis is a compensatory response to improve oxygen transport. The white blood cell count is usually normal, and the platelet count may be normal or reduced.
The increased red blood cell mass may result in an increase in blood viscosity. However, the most likely cause of complications in adults with cyanotic CHD is aggressive phlebotomy or blood loss (184). Most cyanotic patients have compensated erythrocytosis with stable hemoglobin that requires no intervention. Therapeutic phlebotomy, therefore, is usually unnecessary unless the hemoglobin is more than 20 g/dL and the hematocrit is greater than 65% with associated symptoms of hyperviscosity and no evidence of dehydration. At these levels, patients may experience symptoms of headache and poor concentration. These symptoms may be relieved by removal of 1 unit of blood, always with an equal volume replacement of dextrose or saline. The purpose of the phlebotomy is to relieve hyperviscosity symptoms and occasionally, before elective operation, to improve coagulation. Repetitive phlebotomies deplete iron stores and may result in production of iron-deficient red blood cells. Iron deficiency, even in the face of erythrocytosis, is undesirable because of the reduced oxygen-carrying capacity and deformability of red blood cells (microcytes) and increased risk of stroke. A peripheral blood smear and serum ferritin or transferrin saturation will confirm the diagnosis.
The treatment for iron deficiency in a patient with destabilized erythropoiesis is challenging. Oral administration of iron frequently results in a rapid and dramatic increase in red cell mass; therefore, caution should be exercised and hemoglobin monitored. Once the serum ferritin and/or transferrin saturation is within the normal range, iron supplementation may be discontinued. Occasionally, patients are intolerant of oral iron and should be placed on pulses of intravenous iron supplementation instead.
Hemostatic abnormalities have been documented in up to 20% of cyanotic patients. Platelet dysfunction and clotting factor deficiencies combine to produce a bleeding tendency in these patients. Epistaxis, gingival bleeding, menorrhagia, and pulmonary hemorrhage are the most common causes of bleeding. The use of anticoagulants and antiplatelet agents, therefore, is controversial and confined to well-defined indications with careful monitoring of the degree of anticoagulation. For a given concentration of citrate solution, the volume must be adjusted downward to correct for the lower plasma volume in those with high hematocrits.
126.96.36.199. Renal Function
In chronic cyanosis, the renal glomeruli are abnormal, frequently hypercellular, and congested and eventually become sclerotic (185). This results in a reduction of the glomerular filtration rate, increased creatinine levels, and proteinuria. This may cause problems with radiopaque contrast material and dehydration, leading to uremia, oliguria, and even anuria. Thus, patients should be hydrated before procedures that involve contrast media.
Abnormal urate clearance is common, and this in conjunction with an increased turnover of red blood cells leads to hyperuricemia and occasionally gout. Hyperuricemia without gout is usually well tolerated and rarely requires intervention (186). Symptomatic gout should be treated.
Medications that affect renal function, such as ACE inhibitors, diuretics, nonsteroidal antiinflammatory drugs, and select antibiotics, should be given with concern and cautious monitoring. As in all persons proceeding to catheterization, cyanotic patients should have an appropriate assessment of glomerular filtration rate (which may require more than measurement of serum creatinine), and the hydration state should be maximized within the constraints of appropriateness for a safe procedure. A low threshold for the use of renally protective strategies (N-acetylcysteine or bicarbonate administration) should be considered when indicated.
The increased breakdown of red blood cells in chronic cyanosis results in an increased risk of calcium bilirubinate gallstones. Surgical intervention is not recommended until patients become symptomatic (refer to Section 1.7, Recommendations for Noncardiac Surgery).
188.8.131.52. Orthopedic and Rheumatologic Complications
Hypertrophic osteoarthropathy with thickened, irregular periosteum occurs in the setting of cyanotic CHD. This may be accompanied by aching and tenderness, especially in the long bones of the legs.
Scoliosis occurs in a high percentage of patients with cyanotic CHD and is occasionally severe enough to compromise pulmonary function and require surgical intervention. Preoperative evaluation by an ACHD cardiologist and cardiac anesthesiologist is recommended before the operation for scoliosis is undertaken because of the recognized increased risk of surgery in cyanotic patients, especially those with PAH, for which this procedure may be contraindicated.
184.108.40.206. Neurological Complications
Neurological complications include an increased risk for paradoxical cerebral emboli. Brain abscess in cyanotic patients and thromboembolic events in patients with atrial tachycardia or atrial stasis associated with transvenous pacing leads can result in new neurological symptoms. These complications should be suspected in a cyanotic patient with headache, fever, and new neurological symptoms. Substantial cognitive and psychosocial issues are prevalent in this population, as discussed in Section 1.5.2, Recommendations for Psychosocial Issues.
220.127.116.11. Pulmonary Vascular Disease
Pulmonary vascular disease commonly accompanies cyanosis in patients with ACHD. The management of and concerns about pulmonary vascular disease and ACHD are discussed in more detail in a later section (Section 9, Pulmonary Hypertension/Eisenmenger Physiology).
1.12. Recommendations for General Health Issues for Cyanotic Patients
1. Cyanotic patients should drink nonalcoholic and noncaffeinated fluids frequently on long-distance flights to avoid dehydration. (Level of Evidence: C)
1. Supplemental oxygenation may be considered for cyanotic patients during long-distance flights. (Level of Evidence: C)
Cyanotic patients should use only pressurized commercial airplanes. Oxygen therapy, although often unnecessary, may be suggested for prolonged travel. Similarly, residence at high altitude is detrimental for patients with cyanosis. Dehydration should be avoided by frequent fluid intake on long flights and during sports activities.
Competitive sports should be avoided in cyanotic patients (187). Cyanosis is a recognized handicap to fetal growth and development, and pregnancy outcome is impacted, with an increased risk of congestive heart failure, preterm delivery, intrauterine growth retardation, and miscarriage. Increased maternal and fetal mortality are also noted and correlate with the degree of cyanosis, ventricular dysfunction, and pulmonary pressures (117).
1.12.1. Hospitalization and Operation
Cyanotic patients are at high risk during any hospitalization or operation. When hospitalized for medical or surgical problems, these patients should be seen and followed up by an ACHD specialist. Management strategies that should be applied include those likely to reduce the risk of paradoxical emboli related to air in the intravenous lines. Medication adjustment may be needed, with cyanosis taken into account. Early ambulation may prevent venous stasis and thrombophlebitis.
1.12.2. Cardiac Reoperation and Preoperative Evaluation
Although some ACHD patients present without prior intervention, the majority will have undergone 1 or more prior repairs. Review of prior operative notes can provide important insight when a cardiac repair is planned. Repeat sternotomy may be associated with cardiac injury. The heart and great arteries may be closely adherent to the sternum because of the loss of pericardial integrity or presence of conduit material in the anterior mediastinum. In addition, right-sided heart structures may be enlarged or hypertensive, which also increases the potential for injury during sternotomy. Morphological abnormalities of the aorta, pulmonary artery, or ventricle–to–pulmonary artery conduit may also be at increased risk of injury. Peripheral vascular abnormalities may be present secondary to previous cardiac catheterization or operative procedures. For example, the radial pulse may be absent in patients with a prior classic Blalock-Taussig shunt. Femoral artery or vein occlusion may have occurred secondary to prior catheterization procedures or indwelling monitoring lines. Knowledge of the status of femoral or auxiliary vessels before reoperation may be particularly important if cannulation for establishment of cardiopulmonary bypass via these vessels is being planned.
To minimize the potential problems that may arise at the time of rerepair, additional preoperative studies may be necessary. The choice of the various supplemental imaging studies should be individualized on the basis of the surgeon's preference and institutional availability. Imaging studies that are frequently used include ultrasound, cine angiography, or MRI to document patency of cardiac anatomy (or occlusion) and status of femoral or axillary vessels. Coronary angiography or CT angiography is used to identify coronary anomalies or obstructive lesions. CT imaging of the chest may be helpful in identifying the relationship and proximity of the right ventricle, right atrium, aorta, pulmonary artery, or extracardiac conduit to the sternum or anterior chest wall. The importance of reviewing prior surgical notes when a repeat operation is planned cannot be overemphasized.
Men aged 35 years or older, premenopausal women 35 years or older with risk factors for atherosclerosis, and postmenopausal women should be evaluated by cardiac catheterization and coronary angiography to rule out associated coronary artery disease before they undergo reoperative cardiac surgery (112).
1.13. Heart Failure in Adult Congenital Heart Disease
The New York Heart Association classification may be inadequate in ACHD patients, particularly if they are cyanotic. Respiratory physiology in cyanotic heart disease is well understood, and it is known that dyspnea may occur within the first 30 seconds of commencing exercise because of the arrival of hypoxemic and acidotic blood at the central receptors; thus, such dyspnea is not due to “pulmonary congestion,” as is the case in heart failure (188–190). Therefore, cyanotic patients with ACHD may have dyspnea on exertion without having heart failure. It is preferable to use a functional ability or activity index (191). The patient with CHD who survives to adulthood will often have 1 or more substrates for developing the clinical syndrome of heart failure, which may either be right- or left-sided or involve both sides of the circulation. Typical ACHD substrates for late heart failure in ACHD patients are as follows:
• Severe AS and/or regurgitation BAV and variants, subvalvular or supravalvular pathology, superimposed coarctation
• Severe congenital mitral stenosis/regurgitation
• Unoperated ASD or partial AVSD
• D-transposition after Mustard or Senning operation, in which the morphological right ventricle is the systemic ventricle
• Tetralogy of Fallot with early-era surgery, long-standing shunt, or severe pulmonary regurgitation
• Single-ventricle physiology
• Fontan surgery.
Many ACHD patients have experienced a combination of prolonged volume and pressure overload. Factors that predispose to the development of late heart failure include abnormal anatomy, surgical sequelae, and progression of underlying pathology. Myocardial damage during cardiac surgery was more common in patients who had operations during the earlier surgical era, but it may still occur in the present day with long cardiopulmonary bypass time, the need for large patches, or incisional scars (192). The reason for late heart failure in certain subsets of ACHD patients is of intense interest but not completely resolved. For example, anomalies in which the SV is a morphological right ventricle or there is a single ventricle have a higher incidence of myocardial dysfunction over time and with time may develop heart failure pathology (193). The presence of significant tricuspid (especially systemic AV valve) regurgitation is strongly associated with RV dysfunction and may be progressive (194). Inappropriate ventricular hypertrophy or myocardial oxygen supply-demand imbalance that results in myocardial ischemia has also been proposed to be a causative factor (195,196). In some forms of cardiac failure, there is evidence of biventricular interaction such that dysfunction of either ventricle negatively influences the other (ie, ventricular-ventricular dependence) (197,198). A straightforward example of adverse interventricular interaction is seen in right-sided heart volume overload in ASD, which results in changes in left ventricular (LV) shape, end-diastolic volume, and ejection fraction, which will normalize after closure of the defect (197). A recent special report on ventricular form and function, although targeted at the left ventricle, notes a shift from primary emphasis on contractile state and load to newer concepts of interaction and dynamic rearrangement of the myocardial layers, factors that may be altered considerably in CHD (199,200). To these substrates, other possible pathogenetic factors for heart failure can be added, such as the following:
• Prolonged cyanosis
• Prolonged pressure overload (eg, AS and subaortic stenosis [SubAS])
• Prolonged volume overload (eg, aortopulmonary shunt, AV semilunar valve regurgitation, or residual shunt)
• Poor myocardial intraoperative preservation
• Large ventricular septal patch
• Large ventricular incisions/scar
• Residual LVOT or RVOT obstruction (eg, PS/pulmonary regurgitation) or shunts (eg, VSD patch leak)
In addition, the following superimposed diseases or conditions unrelated to ACHD patients that become common in adulthood can contribute to or “tip the balance” toward development of heart failure:
• Acquired valvular heart disease
• Coronary artery disease
• Systemic hypertension
• Diabetes mellitus
• Chronic respiratory disease
• Cardiotoxic chemotherapy/mediastinal irradiation
• Illicit drug use
• Acquired renal or liver disease
• Obstructive sleep apnea
• Hyperthyroidism or hypothyroidism.
One concept that deserves more attention in the field of heart failure and ACHD is that of “ventriculoarterial coupling.” It is well known that increased systemic arterial pressure or isolated systolic hypertension occurs in many individuals as they age and that this has detrimental effects. Changes in aortic diameter, stiffness, and wave reflection increase with age, which leads to an increase in ventricular afterload and may adversely affect late systolic ejection and/or early diastolic relaxation. Such aging changes may be detrimental to a systemic right or single ventricle that is ill prepared for any additional afterload. In addition, a combination of ventricular hypertrophy and arterial stiffening may lead to diastolic heart failure in the presence of preserved ventricular ejection fraction.
Signs of heart failure in ACHD patients may vary from the usual findings in patients with acquired heart disease and heart failure. Cardiorespiratory and ventilatory responses to exercise after a Fontan procedure, for example, are subnormal, including lower than expected V˙o2 max, subnormal cardiac output and heart rate responses to exercise, and an abnormal reduction of resting arterial O2 saturation at peak exercise. After a Fontan or Glenn procedure, interpretation of the jugular venous pressure loses its usual meaning.
The ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the adult appropriately notes that critical assessment of ventricular function is needed in the patient with heart failure (201). It is desirable that assessments of function include quantitative measurements (eg, cardiopulmonary exercise testing with determination of oxygen consumption or cardiac function assessed by echocardiography with specific measures of systolic and diastolic function). Cardiac MRI to assess ventricular anatomy and function, dimensions, myocardial perfusion, and ischemia in adults with unoperated or operated CHD (eg, after atrial switch procedures) may be helpful (202–204). MRI studies of systemic right ventricles and single ventricles may show abnormalities of myocardial twist, torsion, radial motion, shortening, and strain relations (205,206). The frequent presence of abnormal ventricular anatomy warrants the addition of a Doppler echocardiography–derived index of myocardial performance index (or Tei index) or measurement of blood levels of brain natriuretic peptide (BNP) (192–194,207,208).
BNP production is affected by ventricular wall stress (eg, pressure overload such as AS, in which BNP appears to be influenced by both systolic and diastolic load) (209). BNP has been shown to be elevated not only in patients with heart failure and LV systolic dysfunction but also in patients with diastolic dysfunction and in RV dysfunction (198). However, BNP can be elevated in cyanotic heart disease without evidence of heart failure or myocardial dysfunction (210). BNP levels overall have been shown to be predictors of cardiac events (211) and have been shown to aid in emergency department diagnosis of heart failure when the cause of a patient's dyspnea is unclear (212), but their role in outpatient diagnosis and clinical follow-up of heart failure and ACHD remains under investigation. Serial measurement of BNP in patients at risk for the development of heart failure, such as patients with single-ventricle anatomy, may prove useful in guiding intervention.
Many current therapeutic strategies for the treatment of heart failure are directed at blocking activation of the neurohormonal system. The role of such medical treatments (eg, ACE inhibitors, angiotensin receptor blockers, and beta blockers) in the prevention or treatment of heart failure has only been studied in small numbers of ACHD patients. One such report on the use of ACE inhibitors in adults after the Mustard procedure showed no significant change in MRI parameters of RV volumes and ejection fractions or of measured exercise capacity (V˙o2 max, exercise duration, and blood pressure response) for the group as a whole, although there was improvement in some patients; the authors recommended a multiinstitutional prospective trial (53).
Established medical therapy for those with acquired heart disease and heart failure now incorporates medications directed at the renin-angiotensin-aldosterone system and sympathetic nervous systems. Although there exist multiple large, randomized, controlled clinical trials of drugs and other therapeutic interventions for heart failure in acquired heart disease, none have included the ACHD population (213). Thus, one should extrapolate cautiously from heart failure trials in acquired heart disease (214–218).
Aldosterone blockade with spironolactone has been shown in a small number of Fontan patients to improve the protein-losing enteropathy (PLE) syndrome (219). Few clinical trials have addressed the effect of angiotensin receptor blockers on outcomes in any adult patients with CHD. The role of the central and peripheral autonomic nervous system in ACHD patients has received some attention but needs further investigation (220–226). For example, in patients with previously operated tetralogy of Fallot, RVOT reconstruction may have affected cardiac autonomic nervous activity, which may also affect exercise hemodynamics, in part via heart rate recovery, altered respiratory physiology, and a decreased systolic blood pressure response with reduced cardiac output reserve. Critical investigation of various medications and other interventions for the possible treatment or prevention of heart failure in patients after tetralogy of Fallot repair, in patients with diminished systemic right or single-ventricle function, and in patients after a Fontan procedure is needed to optimize outcomes for these patients.
The role of pacemaker therapy in the treatment of cardiac failure is evolving rapidly (71,227). The need for pacing often coincides with worsening hemodynamic status, and it is not always possible to separate cause and effect. Regardless, it is well known that abnormal activation sequences (eg, from RV pacing) may cause a reduction in ventricular function (228,229).
Intraventricular or interventricular dyssynchrony may exacerbate chronic heart failure. Cardiac resynchronization therapy is an accepted means of improving ventricular function in conditions with normal 2-ventricle morphology and is now being proposed for treatment of heart failure in patients with a systemic RV (230). At present, there is no evidence to support its use in any patient with single-ventricle morphology. Current criteria for cardiac resynchronization therapy implantation in patients with normal (2-ventricle) morphology and heart failure include persistent heart failure symptoms despite appropriate medical therapy, QRS duration greater than or equal to 120 milliseconds with left bundle-branch block morphology, and the presence of sinus rhythm.
1.14. Recommendations for Heart and Heart/Lung Transplantation
1. Patients with CHD and heart failure who may require heart transplantation should be evaluated and managed in tertiary care centers with medical and surgical personnel with experience and expertise in the management of both CHD and heart transplantation. (Level of Evidence: C)
2. Patients with CHD and heart or respiratory failure who may require lung or heart/lung transplantation should be evaluated and managed in tertiary care centers with medical and surgical personnel with experience and expertise in the management of CHD and lung or heart/lung transplantation. (Level of Evidence: C)
In ACHD patients, postoperative ventricular failure may occur early after operation but more commonly develops late after operation, often in adulthood. Late systemic ventricular failure can be associated with many congenital diagnoses.
The pretransplantation evaluation involves a multidisciplinary approach that addresses assessment of cardiopulmonary, renal, neurological, hepatic, infectious disease, socioeconomic, and psychological issues. In addition to history and physical examination, diagnostic studies include ECG, echocardiography, chest x-ray, and Holter monitoring. Cardiac catheterization is required to assess pulmonary vascular resistance (PVR) and transpulmonary gradient (231). In addition to cardiac catheterization, MRI or CT angiography is often performed to delineate the anatomy in patients with complex CHD (eg, patients with malposition of the great arteries and/or substernal position of an extracardiac conduit, abnormalities of systemic venous return, and situs abnormalities).
Many patients with long-standing heart failure may have elevated PVR. Consequently, donor right-sided heart failure may result when the heart is abruptly placed proximal to such a high-resistance pulmonary vascular bed. Pharmacological modulation of pulmonary hemodynamics with pulmonary vasodilators during cardiac catheterization helps predict outcome after heart transplantation (232,233). In most centers, a fixed PVR index of 6 units or more or a transpulmonary gradient greater than 15 mm Hg that does not respond to vasodilator therapy (oxygen, nitric oxide, milrinone, or dobutamine) is a contraindication to cardiac transplantation alone, although transplantation from a rare donor with PAH in a Domino procedure with heart/lung transplantation in 1 recipient followed by transplantation of the recipient's heart into another recipient may still be successful.
Contraindications to cardiac transplantation include the following:
• Active infection
• Positive serology for human immunodeficiency virus or hepatitis C infections
• Severe metabolic disease
• Multiple other severe congenital anomalies
• Multisystem organ failure
• Active malignancy
• Cognitive or behavioral disability that interferes with compliance.
Heart/lung transplantation is usually reserved for patients with uncorrectable or previously repaired or palliated CHD associated with significant pulmonary vascular obstructive disease, such as single-ventricle physiology with pulmonary vascular disease or LV dysfunction with associated pulmonary vascular disease. When a simple cardiac defect is present, such as ASD, VSD, or PDA, the cardiac defect can often be repaired at lung transplantation (234). In the presence of more complex intracardiac abnormalities, combined heart/lung transplantation is usually most appropriate.
Previous thoracotomies are not an absolute contraindication to transplantation, but in the presence of chronic cyanosis, vascular collaterals may lead to fatal hemorrhagic complications. The absence of detectable recurrence of malignancy for 5 years may permit successful transplantation. Obesity is a relative contraindication to transplantation.
Survival rates after heart transplantation have improved over the years, and the current predicted posttransplantation half-life (the time at which 50% of those with transplanted organs remain alive, or median survival) for the entire cohort of pediatric and adult heart recipients is 10 years, with a half-life of 13 years for those who survive the first year; however, having ACHD as an indication for transplant increases that risk during the first year by 2-fold (235).
Advances in selection, technique, and management of patients undergoing lung or heart/lung transplant have resulted in significant improvement in survival. Overall, survival after pediatric lung transplantation as reported by the International Society of Heart and Lung Transplant registry is approximately 75% at 1 year and 60% at 2 years (236). The most common cause of mortality in the first month after lung transplantation is acute graft failure; from 1 month to 1 year after transplantation, infection is the leading cause of death. From 1 to 3 years after lung transplantation, chronic rejection or bronchiolitis obliterans is the leading cause of death. Beyond this time frame, main causes of death include chronic rejection and infection. The outcome for heart/lung transplantation is similar to that for lung transplantation.
Actuarial survival at 10 years after heart/lung transplantation is 20%. Results of lung and heart/lung transplantation for PAH and ACHD are comparable to those reported for children, with an increased risk of early mortality related to perioperative complications and complexity compared with transplantation for obstructive pulmonary disease or cystic fibrosis. Outcomes for lung transplantation and cardiac repair are comparable to those for heart/lung transplantation in the treatment of PAH and CHD (237).
2. Atrial Septal Defect
One of the most common adult congenital heart defects, an ASD is a persistent communication between the atria. There are several different types of ASD: the secundum ASD in the region of the fossa ovalis (75% of cases), the primum ASD (15% to 20%) positioned inferiorly near the crux of the heart, the sinus venosus ASD (5% to 10%) located superiorly near the superior vena caval entry or inferiorly near the inferior vena caval entry, and the uncommon coronary sinus septal defect (less than 1%), which causes shunting through the ostium of the coronary sinus (238). The patent foramen ovale (PFO) is a flaplike communication in which the septum primum covering the fossa ovalis overlaps the superior limbic band of the septum secundum. In some patients, the septum primum or secundum is aneurysmal and may have multiple small fenestrations.
2.1.1. Associated Lesions
ASD can be associated with additional malformations in nearly 30% of cases (Table 9) (239). As a form of AVSD, the primum ASD is nearly always accompanied by a cleft in the anterior mitral valve leaflet. Discrete SubAS may develop postoperatively. Sinus venosus defects frequently have partial anomalous venous drainage of the right pulmonary veins. This association is present in a small number of patients with secundum ASDs as well. Mitral valve prolapse is frequently seen in patients with ASD. Valvular pulmonic stenosis is frequently described in association with ASD, but in some cases, there is a mild RV outflow gradient that is caused by increased flow but not a structural valve abnormality (240,241).
Coronary sinus septal defect, a defect in the roof of the coronary sinus and not technically an ASD, may be accompanied by partial or total anomalous pulmonary venous connection and/or a persistent left superior vena cava draining to the coronary sinus.
2.2. Clinical Course
2.2.1. Unrepaired Atrial Septal Defect
The consequence of left-to-right shunt across an ASD is RV volume overload and pulmonary overcirculation. Large atrial shunts lead to symptoms from excess pulmonary blood flow and right-sided heart failure, including frequent pulmonary infections, fatigue, exercise intolerance, and palpitations. Atrial arrhythmias—atrial flutter, atrial fibrillation, and sick sinus syndrome—are a common result of long-standing right-sided heart volume and pressure overload. Flow-related PAH accompanies large left-to-right shunts, and pulmonary vascular obstructive disease may develop in adult years but occurs much later with ASD than with high-pressure left-to-right shunts such as VSD or PDA. Paradoxical embolism from peripheral venous or pelvic vein thromboses, atrial arrhythmias, unfiltered intravenous infusions, or indwelling venous catheters is a risk for all defects regardless of size (242–244).
The initial presentation in adulthood most commonly includes symptoms of dyspnea and palpitations (245,246). Other modes of presentation in the previously undiagnosed adult with an ASD include cardiomegaly on routine chest x-ray, a more audible murmur during pregnancy, new onset of atrial flutter/fibrillation, or a paradoxical embolic event. Patients with small defects (less than 10 mm) may remain asymptomatic well into the fourth and fifth decade of life (236,246); however, symptoms may develop with increasing age even with small defects owing to an increase in shunting caused by a decrease in LV compliance secondary to coronary artery disease, acquired valvular disease, or hypertension.
2.3. Recommendations for Evaluation of the Unoperated Patient
1. ASD should be diagnosed by imaging techniques with demonstration of shunting across the defect and evidence of RV volume overload and any associated anomalies. (Level of Evidence: C)
2. Patients with unexplained RV volume overload should be referred to an ACHD center for further diagnostic studies to rule out obscure ASD, partial anomalous venous connection, or coronary sinoseptal defect. (Level of Evidence: C)
1. Maximal exercise testing can be useful to document exercise capacity in patients with symptoms that are discrepant with clinical findings or to document changes in oxygen saturation in patients with mild or moderate PAH. (Level of Evidence: C)
2. Cardiac catheterization can be useful to rule out concomitant coronary artery disease in patients at risk because of age or other factors. (Level of Evidence: B)
1. In younger patients with uncomplicated ASD for whom imaging results are adequate, diagnostic cardiac catheterization is not indicated. (Level of Evidence: B)
2. Maximal exercise testing is not recommended in ASD with severe PAH. (Level of Evidence: B)
The diagnostic workup for a patient with a suspected ASD is directed at defining the presence, size, and location of the ASD; the functional effect of the shunt on the right and left ventricles and the pulmonary circulation; and any associated lesions.
2.3.1. Clinical Examination
Clinical findings include a precordial lift, systolic pulmonary flow murmur, and fixed splitting of the second heart sound (although fixed splitting is not invariable). With large shunts, a diastolic flow rumble across the tricuspid valve is present.
The ECG often shows right-axis deviation, right atrial enlargement, incomplete right bundle-branch block (secundum ASD), superior left-axis deviation (primum ASD), or an abnormal P-wave axis (superiorly located sinus venosus ASD). Complete heart block may be present in association with familial ASD (247). The superior left axis with RV conduction delay seen in primum ASD is due to the anatomic position of the conduction bundles and should not be confused with bifascicular block.
2.3.3. Chest X-Ray
The chest x-ray may show RV and right atrial enlargement, a prominent pulmonary artery segment, and increased pulmonary vascularity.
A TTE is the primary diagnostic imaging modality for ASD. The study should include 2-dimensional imaging of the atrial septum from the parasternal, apical, and subcostal views with color Doppler demonstration of shunting. Subcostal views with deep inspiration and high right parasternal views can be particularly helpful for imaging ASD in adults. The entire atrial septum from the orifice of the superior vena cava to the orifice of the inferior vena cava should be visualized to detect sinus venosus defects or the extension of large secundum defects in these regions. A TEE may be necessary to identify the connection of all pulmonary veins in patients with ASD. In adults with poor-quality transthoracic images, TEE may be necessary to adequately image the atrial septum (248–251), because it provides exact localization and sizing of the ASD, as well as measurement of septal rims, each of which is important for decision making.
A large coronary sinus orifice with evidence of atrial shunting may indicate a defect in the roof of the coronary sinus (eg, sinoseptal defects). Thus, the entire coronary sinus roof should be imaged when this is suspected. When a coronary sinoseptal defect is associated with lesions that cause right-to-left shunting, the orifice of the coronary sinus may not be enlarged and the defect not recognized until after definitive surgery, at which time a left-to-right shunt may occur. With PAH, the low velocity of the shunt flow across the coronary sinoseptal defect may be difficult to distinguish from other low-velocity flow within the atria.
Right atrial and RV enlargement with diastolic flattening and paradoxical motion of the interventricular septum are evidence of RV volume overload and a significant left-to-right shunt. The RV systolic pressure should be estimated from the peak velocity of the tricuspid regurgitant jet if present. Two-dimensional imaging should assess associated lesions such as mitral valve prolapse, cleft mitral valve, anomalous pulmonary veins, and PS, and their functional significance should be determined by color and spectral Doppler.
Contrast echocardiography with intravenous agitated saline injection is used to confirm the presence of a right-to-left atrial shunt if imaging and color Doppler are not conclusive (252). Additionally, the presence of negative contrast in the right atrium may be helpful in identifying a left-to-right shunt. If a left-to-right shunt or RV volume overload is recognized but unexplained, the patient should be referred to an ACHD center for further imaging studies.
2.3.5. Magnetic Resonance Imaging
MRI provides an additional noninvasive imaging modality if findings by echocardiography are uncertain. Direct visualization of the defect and pulmonary veins is possible, RV volume and function can be quantified, and estimates of shunt size can also be obtained (253–255). Contrast-enhanced ultrafast cine CT can also provide diagnostic information, although the radiation exposure limits its utility in most cases (256).
Diagnostic cardiac catheterization is not required for uncomplicated ASDs in younger patients with adequate noninvasive imaging (257,258). It is generally reserved for investigation of coronary artery disease in those patients at risk by virtue of age or family history and for whom surgical intervention is planned and to assess PVR and reactivity in patients with significant PAH. Catheterization may also be required to evaluate ASD size, pulmonary venous return, and associated valvular disease if noninvasive methods have been unable to provide this information. In most instances, catheterization is now performed in conjunction with device closure of the defect.
2.3.6. Exercise Testing
Exercise testing can be useful to document exercise capacity in patients with symptoms that are discrepant with clinical findings or to document changes in oxygen saturation in patients with PAH. Maximal exercise testing is not recommended in ASD with severe PAH, however.
2.4. Diagnostic Problems and Pitfalls
The gradual onset of symptoms and the subtlety of the physical findings with ASDs often lead to late diagnosis, which puts the patient at greater risk for developing PAH, arrhythmia, and paradoxical embolism. False-positive diagnosis of ASD can result from either apparent septal dropout on 2-dimensional echocardiography images or misinterpretation by color Doppler of vena caval inflow as shunt flow. The use of contrast echocardiography or TEE will prevent false-positive interpretations. Patients with partial anomalous pulmonary venous drainage without an ASD will have RV volume overload and may be erroneously presumed to have an ASD.
False-negative diagnoses are relatively common in adults with poor-quality transthoracic images, especially patients with sinus venosus ASD. Because of its superior location, the superior sinus venosus defect is most often missed by TTE (248). Patients with an unexplained RV volume overload by TTE should be studied by TEE or another imaging modality to fully evaluate the atrial septum and pulmonary veins and to rule out defects in the roof of the coronary sinus.
2.5. Management Strategies
2.5.1. Recommendations for Medical Therapy
1. Cardioversion after appropriate anticoagulation is recommended to attempt restoration of the sinus rhythm if atrial fibrillation occurs. (Level of Evidence: A)
2. Rate control and anticoagulation are recommended if sinus rhythm cannot be maintained by medical or interventional means. (Level of Evidence: A)
Patients with small shunts and normal RV size are generally asymptomatic and require no medical therapy. Routine follow-up of the patient with a small ASD without evidence of RV enlargement or PAH should include assessment of symptoms, especially arrhythmias, and possible paradoxical embolic events. A repeat echocardiogram should be obtained every 2 to 3 years to assess RV size and function and pulmonary pressure. Reductions in LV compliance related to hypertension, coronary artery disease, or acquired valvular disease increase the degree of left-to-right shunt across an existing ASD.
Atrial arrhythmias should be treated to restore and maintain sinus rhythm if possible (259). If atrial fibrillation occurs, both antiarrhythmic therapy and anticoagulation should be recommended.
ASDs that are large enough to cause PAH should be closed provided there is evidence of pulmonary vascular reactivity and a net left-to-right shunt. Medical therapy for PAH is indicated only for those patients who are considered to have irreversible PAH and therefore are not eligible for ASD closure (refer to Section 9, Pulmonary Hypertension/Eisenmenger Physiology, for more extensive discussion of the treatment of PAH).
2.5.2. Recommendations for Interventional and Surgical Therapy
1. Closure of an ASD either percutaneously or surgically is indicated for right atrial and RV enlargement with or without symptoms. (Level of Evidence: B)
2. A sinus venosus, coronary sinus, or primum ASD should be repaired surgically rather than by percutaneous closure. (Level of Evidence: B)
3. Surgeons with training and expertise in CHD should perform operations for various ASD closures. (Level of Evidence: C)
1. Surgical closure of secundum ASD is reasonable when concomitant surgical repair/replacement of a tricuspid valve is considered or when the anatomy of the defect precludes the use of a percutaneous device. (Level of Evidence: C)
2. Closure of an ASD, either percutaneously or surgically, is reasonable in the presence of:
a. Paradoxical embolism. (Level of Evidence: C)
b. Documented orthodeoxia-platypnea. (Level of Evidence: B)
1. Closure of an ASD, either percutaneously or surgically, may be considered in the presence of net left-to-right shunting, pulmonary artery pressure less than two thirds systemic levels, PVR less than two thirds systemic vascular resistance, or when responsive to either pulmonary vasodilator therapy or test occlusion of the defect (patients should be treated in conjunction with providers who have expertise in the management of pulmonary hypertensive syndromes). (Level of Evidence: C)
2. Concomitant Maze procedure may be considered for intermittent or chronic atrial tachyarrhythmias in adults with ASDs. (Level of Evidence: C)
1. Patients with severe irreversible PAH and no evidence of a left-to-right shunt should not undergo ASD closure. (Level of Evidence: B)
Surgical closure has been the “gold standard” form of treatment, with excellent late outcome. A surgeon not trained in CHD should be cautious when planning to close a secundum ASD, because the intraoperative discovery of an unexpected primum ASD or partial anomalous pulmonary venous drainage can present challenges.
Primary operation includes pericardial patch closure or direct suture closure. Tricuspid valve repair should be performed for significant tricuspid regurgitation (TR). Anomalous pulmonary venous drainage should be repaired. The Warden procedure (translocation of the superior vena cava to the right atrial appendage) may be applied to the sinus venosus ASD when the anomalous pulmonary venous drainage enters the mid or upper superior vena cava. A concomitant Maze procedure may be performed for intermittent/chronic atrial fibrillation/flutter. The surgical approach can be by right thoracotomy or sternotomy, and more limited incisions are feasible with either approach.
Early mortality is approximately 1% in the absence of PAH or other major comorbidities. Long-term follow-up is excellent, and preoperative symptoms decrease or abate. The incidence of atrial fibrillation/flutter is reduced when concomitant antiarrhythmic procedures (eg, Maze) are performed; however, atrial arrhythmias may occur de novo after repair.
The need for reoperation of residual/recurrent ASD is uncommon. Superior vena cava stenosis or pulmonary vein stenosis may occur after closure of sinus venosus ASD.
2.5.3. Indications for Closure of Atrial Septal Defect
Small ASDs with a diameter of less than 5 mm and no evidence of RV volume overload do not impact the natural history of the individual and thus may not require closure unless associated with paradoxical embolism. Larger defects with evidence of RV volume overload on echocardiography usually only cause symptoms in the third decade of life, and closure is usually indicated to prevent long-term complications such as atrial arrhythmias, reduced exercise tolerance, hemodynamically significant TR, right-to-left shunting and embolism during pregnancy, overt congestive cardiac failure, or pulmonary vascular disease that may develop in up to 5% to 10% of affected (mainly female) individuals.
2.5.4. Catheter Intervention
The development of percutaneous transcatheter closure techniques has provided an alternative method of closure for uncomplicated secundum ASDs with appropriate morphology (260–262). Currently, the majority of secundum ASDs can be closed with a percutaneous catheter technique. When this is not feasible or is not appropriate, surgical closure is recommended.
Sinus venosus, coronary sinus, and primum defects are not amenable to device closure. An ASD with a large septal aneurysm or a multifenestrated atrial septum requires careful evaluation by and consultation with interventional cardiologists before device closure is selected as the method of repair.
2.5.5. Key Issues to Evaluate and Follow-Up
Key issues to evaluate and monitor in adults with ASD are listed in Table 10.
2.6. Recommendations for Postintervention Follow-Up
1. Early postoperative symptoms of undue fever, fatigue, vomiting, chest pain, or abdominal pain may represent postpericardiotomy syndrome with tamponade and should prompt immediate evaluation with echocardiography. (Level of Evidence: C)
2. Annual clinical follow-up is recommended for patients postoperatively if their ASD was repaired as an adult and the following conditions persist or develop:
a. PAH. (Level of Evidence: C)
b. Atrial arrhythmias. (Level of Evidence: C)
c. RV or LV dysfunction. (Level of Evidence: C)
d. Coexisting valvular or other cardiac lesions. (Level of Evidence: C)
3. Evaluation for possible device migration, erosion, or other complications is recommended for patients 3 months to 1 year after device closure and periodically thereafter. (Level of Evidence: C)
4. Device erosion, which may present with chest pain or syncope, should warrant urgent evaluation. (Level of Evidence: C)
Follow-up for patients after device closure requires clinical assessment of symptoms of arrhythmia, chest pain, or embolic events and echocardiographic surveillance for device position, residual shunting, and complications such as thrombus formation or pericardial effusion. The frequency of echocardiographic follow-up is usually at 24 hours, 1 month, 6 months, and 1 year and at regular intervals thereafter.
Pericardial effusions and cardiac tamponade may occur up to several weeks after surgical repair of ASDs and should be evaluated by clinical examination and echocardiography before hospital discharge and at the early postoperative visits. Patients and their primary care physicians should be instructed to report fever or unusual symptoms of chest or abdominal pain and vomiting or undue fatigue in the first weeks after surgery, because they might represent early signs of cardiac tamponade. Assessment of pulmonary pressure, RV function, and residual atrial shunting should also be made during follow-up echocardiography. Clinical and ECG surveillance for recurrent or new-onset arrhythmia is an important feature of postoperative evaluation. Periodic long-term clinical follow-up is required for patients postoperatively if their ASD was repaired as an adult, if PAH was present preoperatively, if there were atrial arrhythmias either preoperatively or postoperatively, if there was RV or LV dysfunction preoperatively or postoperatively, or if there are coexisting valvular or other cardiac lesions. Patients with ASD who have undergone surgical closure in childhood are generally free of late complications.
2.6.1. Endocarditis Prophylaxis
Endocarditis does not occur in patients with isolated ASDs and is usually associated with concomitant valvular lesions, such as a cleft mitral valve (94). Endocarditis prophylaxis is therefore not indicated for isolated ASDs before or after surgery except for the first 6 months after closure (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).
2.6.2. Recommendation for Reproduction
1. Pregnancy in patients with ASD and severe PAH (Eisenmenger syndrome) is not recommended owing to excessive maternal and fetal mortality and should be strongly discouraged. (Level of Evidence: A)
Pregnancy in patients with ASDs is generally well tolerated, with no maternal mortality and no significant maternal or fetal morbidity. Although the left-to-right shunt may increase with the increase in cardiac output during pregnancy, this is counterbalanced by the decrease in peripheral resistance.
Women with large shunts and PAH may experience arrhythmias, ventricular dysfunction, and progression of PAH. Pregnancy in patients with ASD and severe PAH (Eisenmenger syndrome) is contraindicated owing to excessive maternal and fetal mortality and should be strongly discouraged (263,264). Paradoxical embolism may occasionally be encountered in small and large ASDs (134,265).
Familial occurrence of secundum ASDs is well recognized, and in some kindreds, a defect has been localized to chromosome 5 (266). Familial ASD with AV conduction defect is an autosomal dominant trait, with mutations in the cardiac homeobox transcription factor gene NKX2–5 (267,268).
The risk of transmission of CHD to offspring of women with sporadic ASD is estimated at 8% to 10% (133,269). Genetic syndromes with skeletal abnormalities associated with ASD include a variety of heart-hand syndromes, of which Holt-Oram syndrome is best known (270–272). Both secundum and primum ASDs are associated with trisomy 21 (Down syndrome). Because of the possibility of familial occurrence, a careful family history should be taken in patients with ASD, and parents and offspring should be evaluated clinically for possible septal defect, conduction disturbances, and skeletal anomalies.
Patients with small ASDs and without PAH have normal exercise capacity and do not need any limitation of physical activity. In those patients with large left-to-right shunts, exercise is often self-limited owing to decreased cardiopulmonary function (273). Symptomatic supraventricular or ventricular arrhythmias may also compromise exercise capacity and impose limitations on engagement in competitive sports. Patients with significant PAH (peak systolic pulmonary artery pressure greater than 40 mm Hg) should limit their activity to low-intensity sports. Severe PAH with right-to-left shunting is usually self-limiting, but participation in athletics or active physical effort should be avoided (274).
3. Ventricular Septal Defect
VSD is the most common congenital heart defect at birth (275) and presents in approximately 3.0 to 3.5 infants per 1000 live births. Because there is a high incidence of spontaneous closure of small VSDs, the incidence is much less in older infants and particularly in adults (276,277).
There are 4 anatomic types of VSDs (278–280), with multiple synonyms for each type. In an effort to establish a unified reporting system, the Society for Thoracic Surgery's Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery developed a classification scheme, as shown in Table 11.
Type 1 VSDs lie in the outflow portion of the RV and account for approximately 6% of defects in non-Asian populations but up to 33% in Asian patients (278). Spontaneous closure of this defect is uncommon.
Type 2 or perimembranous VSDs are the most common defects, and almost 80% of defects are in this location. This defect is in the membranous septum and is adjacent to the septal leaflet of the tricuspid valve, which can become adherent to the defect, thus forming a pouch or “aneurysm” of the ventricular septum. This pouch will limit left-to-right shunting and can result in partial or complete closure of the defect. On the LV side of the septum, the defect is adjacent to the aortic valve.
Type 3 or inlet VSDs occur in the lower part of the right ventricle and adjacent to the tricuspid valve (278–280). These defects typically occur in patients with Down syndrome.
Type 4 or muscular VSDs can be located centrally (midmuscular), apically, or at the margin of the septum and RV free wall. They can be multiple in number. Spontaneous closure is common, and although these defects can account for up to 20% of VSDs in infants, the incidence is much lower in adults (276–278).
3.1.1. Associated Lesions
Although VSD is most often an isolated lesion, it is a common component of complex abnormalities such as conotruncal defects (eg, tetralogy of Fallot, TGA). VSD can also be associated with left-sided obstructive lesions such as SubAS and coarctation of the aorta. A subpulmonary (supracristal) VSD is often associated with progressive aortic valve regurgitation caused by prolapse of the aortic cusp (usually right) through the defect.
3.2. Clinical Course (Unrepaired)
It is unlikely for an adult with an isolated VSD to present with no prior workup/diagnosis. Possible scenarios include the following:
• An asymptomatic patient with a systolic murmur previously thought to be an innocent murmur
• Fever and bacteremia secondary to IE
• A new diastolic murmur of AR secondary to aortic valve prolapse
• Cyanosis and exercise intolerance secondary to the progressive development of pulmonary vascular disease.
Clinical presentation in an isolated VSD depends largely on defect size and PVR. Small defects that are less than or approximately equal to 25% the size of the aortic annulus diameter have small left-to-right shunts, no left ventricle volume overload, and no PAH and present as systolic murmurs.
VSDs that are more than 25% but less than 75% of the aortic diameter can be classified as moderate in size, with small to moderate left-to-right shunts, mild to moderate LV volume overload, and mild or no PAH. Patients may remain asymptomatic or develop symptoms of mild congestive heart failure. Symptoms usually abate with medical treatment and with time as the size of the VSD decreases in absolute terms or relative to increasing body size.
If the defect is large (greater than or equal to 75% of the aortic diameter), there is usually a moderate to large left-to-right shunt, LV volume overload, and PAH. Most adult patients with large VSDs will have a history of congestive heart failure in infancy. Rarely, patients with large VSDs do not develop large left-to-right shunts and do not have the normal postnatal fall in PVR. They can present with right-to-left shunting and Eisenmenger syndrome later in childhood or as adolescents or young adults. Key issues to follow in patients with VSD are summarized in Table 12. Patients with a small VSD who develop endocarditis may present with pulmonary embolism or cerebral abscess. Spontaneous closure of small defects can occur at any age but most commonly occurs in infancy (277,281,282). Postsurgical presentations include signs and symptoms associated with IE, AR, heart block, LV dysfunction, PAH, TR, recurrent VSD, and ventricular arrhythmias.
3.3. Clinical Features and Evaluation of the Unoperated Patient
3.3.1. Clinical Examination
VSD is characterized clinically by a systolic murmur that is usually maximal at the left lower sternal border. When RV pressure is low, the VSD murmur is blowing and pansystolic. With incremental increases in RV pressure, the murmur is shorter, softer, and lower pitched. Small, muscular VSDs are usually very high-pitched and occupy early systole only because muscular contraction closes the defect.
In patients with large VSD and significant PAH, the ECG will show biventricular hypertrophy or isolated RV hypertrophy, depending on the extent to which the LVOT has diminished in response to the reduction in left-to-right shunt.
3.3.3. Chest X-Ray
Patients with a small VSD will have a normal chest x-ray. The presence of a significant left-to-right shunt will create the appearance of left atrial and LV enlargement and increased pulmonary vascular markings. Patients with significant PAH will not demonstrate LV enlargement but will have a prominent pulmonary artery segment and diminished pulmonary vascular markings at the periphery of the lung.
Echocardiography-Doppler is the mainstay of modern diagnosis. Transthoracic echocardiographic studies are almost always diagnostic in children and adolescents and in most adults with good echocardiographic windows. Data to be obtained include the number of defects, location of defect(s), chamber sizes, ventricular function, presence or absence of aortic valve prolapse and/or regurgitation, presence or absence of RV or LV outflow obstruction, and presence or absence of TR. Estimation of RV systolic pressure from TR jet, VSD jet, and/or septal configuration should be a part of the study. In adults with poor echocardiographic windows, TEE may be necessary.
Echocardiography-Doppler of postoperative patients should focus on the presence or absence and location of residual shunting and the evaluation of pulmonary artery pressure by TR or pulmonary regurgitation jet velocity. In addition, patients should be evaluated for AR, ventricular function, and RV or LV outflow obstruction.
3.3.5. Magnetic Resonance Imaging/Computed Tomography
MRI or CT may be useful, if local expertise in cardiac studies is available, for the following:
• Assessment of pulmonary artery, pulmonary venous, and aortic anatomy if there are coexisting lesions
• To confirm the anatomy of unusual VSDs such as inlet or apical defects not well seen by echocardiography.
3.3.6. Recommendations for Cardiac Catheterization
1. Cardiac catheterization to assess the operability of adults with VSD and PAH should be performed in an ACHD regional center in collaboration with experts. (Level of Evidence: C)
1. Cardiac catheterization can be useful for adults with VSD in whom noninvasive data are inconclusive and further information is needed for management. Data to be obtained include the following:
a. Quantification of shunting. (Level of Evidence: B)
b. Assessment of pulmonary pressure and resistance in patients with suspected PAH. Reversibility of PAH should be tested with various vasodilators. (Level of Evidence: B)
c. Evaluation of other lesions such as AR and double-chambered right ventricle. (Level of Evidence: C)
d. Determination of whether multiple VSDs are present before surgery. (Level of Evidence: C)
e. Performance of coronary arteriography is indicated in patients at risk for coronary artery disease. (Level of Evidence: C)
f. VSD anatomy, especially if device closure is contemplated. (Level of Evidence: C)
3.4. Diagnostic Problems and Pitfalls
Problems and pitfalls in the diagnosis of adults with VSDs include the following:
• Patients with loud murmur of a known small VSD may develop double-chambered right ventricle or SubAS with little appreciable change in murmur.
• Patients with a small VSD and aortic valve prolapse may develop progressive AR.
• Patients with unrecognized RV outflow obstruction associated with a VSD may have a high-velocity TR jet and may be assumed to have PAH.
• A VSD jet may be mistaken for a TR jet in a patient with normal pulmonary pressure assumed to have PAH.
3.5. Management Strategies
3.5.1. Recommendation for Medical Therapy
1. Pulmonary vasodilator therapy may be considered for adults with VSDs with progressive/severe pulmonary vascular disease (refer to Section 9, Pulmonary Hypertension/Eisenmenger Physiology). (Level of Evidence: B)
3.5.2. Recommendations for Surgical Ventricular Septal Defect Closure
1. Surgeons with training and expertise in CHD should perform VSD closure operations. (Level of Evidence: C)
2. Closure of a VSD is indicated when there is a Qp/Qs (pulmonary–to–systemic blood flow ratio) of 2.0 or more and clinical evidence of LV volume overload. (Level of Evidence: B)
3. Closure of a VSD is indicated when the patient has a history of IE. (Level of Evidence: C)
1. Closure of a VSD is reasonable when net left-to-right shunting is present at a Qp/Qs greater than 1.5 with pulmonary artery pressure less than two thirds of systemic pressure and PVR less than two thirds of systemic vascular resistance. (Level of Evidence: B)
2. Closure of a VSD is reasonable when net left-to-right shunting is present at a Qp/Qs greater than 1.5 in the presence of LV systolic or diastolic failure. (Level of Evidence: B)
1. VSD closure is not recommended in patients with severe irreversible PAH. (Level of Evidence: B)
Primary operation for isolated VSD includes patch closure, usually with a synthetic material (eg, Dacron, polytetrafluoroethylene [Gore-Tex]), and, rarely, primary closure. Careful intraoperative inspection of the muscular septum by TEE is indicated to rule out associated VSDs that might manifest by shunting only after closure of the dominant VSD. Associated RV outflow obstruction should be treated with resection or RV outflow patch enlargement, AR by aortic valve replacement (AVR), and SubAS usually by resection of a subaortic membrane and rarely by a Konno procedure tricuspid valve repair if there is associated significant TR.
Early mortality is approximately 1% in the absence of elevated PVR. Late survival is excellent when ventricular function is normal. PAH may regress, progress, or remain unchanged. Atrial fibrillation may occur and is more likely if there has been chronic volume overload resulting in left atrial dilatation. Complete heart block may occur early or late after surgical repair. Ventricular arrhythmias are uncommon unless repair is performed late in life. The need for reoperation for a residual VSD is uncommon. Late reoperation is occasionally required for TR or AR.
3.5.3. Recommendation for Interventional Catheterization
1. Device closure of a muscular VSD may be considered, especially if the VSD is remote from the tricuspid valve and the aorta, if the VSD is associated with severe left-sided heart chamber enlargement, or if there is PAH. (Level of Evidence: C)
Indications for catheter device closure of VSD include residual defects after prior attempts at surgical closure, restrictive VSDs with a significant left-to-right shunt, trauma, or iatrogenic artifacts after surgical replacement of the aortic valve. Indications for closure of restrictive VSDs in the adult population include a history of bacterial endocarditis or a hemodynamically significant left-to-right shunt (Qp/Qs greater than 1.5:1).
Percutaneous closure of VSD offers an attractive alternative to surgical management in patients with increased surgical risk factors, multiple previous cardiac surgical interventions, poorly accessible muscular VSDs, or “Swiss cheese”–type VSDs. At the time of this writing, US Food and Drug Administration approval for device closure of VSDs in the United States is limited to closure of muscular VSDs. Experience with percutaneous closure of other types of VSDs has been obtained at centers outside the United States or in centers with investigational protocols.
Complications have been reported in as many as 10.7% of patients and most frequently include rhythm and conduction abnormalities, as well as hypotensive episodes or blood loss (283); however, complications are significantly associated with a lower patient weight (below 10 kg), and therefore the adult population is likely to represent a lower-risk group for percutaneous closure of muscular VSDs. Complications after closure of perimembranous VSDs predominantly include rhythm and conduction abnormalities, as well as the potential for new or increased AR or TR, which is usually of a trivial or mild degree.
Success rates of the procedure are high, with closure rates with the membranous device of up to 92% at 15 minutes after device implantation and a 92% rate of complete closure at the 12-month follow-up for device closure of muscular VSD. These results, unfortunately, are not matched in patients undergoing closure of a postinfarct VSD because of the often moribund status of these patients and the tendency of the VSD to enlarge over time owing to ongoing necrosis.
3.6. Key Issues to Evaluate and Follow-Up
3.6.1. Recommendations for Surgical and Catheter Intervention Follow-Up
1. Adults with VSD with residual heart failure, shunts, PAH, AR, or RVOT or LVOT obstruction should be seen at least annually at an ACHD regional center. (Level of Evidence: C)
2. Adults with a small residual VSD and no other lesions should be seen every 3 to 5 years at an ACHD regional center. (Level of Evidence: C)
3. Adults with device closure of a VSD should be followed up every 1 to 2 years at an ACHD center depending on the location of the VSD and other factors. (Level of Evidence: C)
Adults with no residual VSD, no associated lesions, and normal pulmonary artery pressure do not require continued follow-up at a regional ACHD center except on referral from their cardiologist or physician. Patients who develop bifascicular block or transient trifascicular block after VSD closure are at risk in later years for the development of complete heart block and should be followed up yearly by history and ECG and have periodic ambulatory monitoring and/or exercise testing.
3.6.2. Recommendation for Reproduction
1. Pregnancy in patients with VSD and severe PAH (Eisenmenger syndrome) is not recommended owing to excessive maternal and fetal mortality and should be strongly discouraged. (Level of Evidence: A)
Women with small VSDs, no PAH, and no associated lesions have no increased cardiovascular risk for pregnancy. Women with PAH should be counseled against pregnancy (refer to Section 9, Pulmonary Hypertension/Eisenmenger Physiology).
Pregnancy is generally well tolerated, with no maternal mortality and no significant maternal or fetal morbidity. Although the left-to-right shunt may increase with the increase in cardiac output during pregnancy, this is counterbalanced by the decrease in peripheral resistance. Women with large shunts and PAH may experience arrhythmias, ventricular dysfunction, and progression of PAH.
No activity restrictions are indicated for patients with small VSDs, no associated lesions, and normal ventricular function. If pulmonary vascular disease is present, activity is usually self-restricted, but patients should be advised against strenuous exercise or travel to altitudes above 5000 feet. Long-distance air travel should be approached with caution to avoid dehydration, with specific recommendation by an ACHD specialist concerning the need for supplemental oxygen (refer to Section 9, Pulmonary Hypertension/Eisenmenger Physiology).
4. Atrioventricular Septal Defect
The terms AVSD, AV canal defect, and endocardial cushion defect can be used interchangeably to describe this group of defects. The basic morphology of AVSD includes a large, central defect that may lie above the AV valve (refer to Section 2, Atrial Septal Defect) or may extend to variable degrees above and below the AV valve; therefore, the interventricular communication can range from large to small. There is a common AV valve annulus that stretches across both ventricles. There may be a common superior leaflet, or the superior leaflet may be separated at its distal margin into right and left components. The AV valve may be misaligned with respect to the ventricles, in association with hypoplasia of the right or left ventricle. The left AV valve is a trileaflet valve made of superior and inferior bridging leaflets separated by a mural leaflet. There may be abnormal lateral rotation of the posteromedial papillary muscle. Most complete AVSDs are in Down syndrome patients (more than 75%). Most partial AVSDs occur in non–Down syndrome patients (more than 90%).
4.2. Associated Lesions
Tetralogy of Fallot and other conotruncal anomalies and heterotaxy syndromes also occur in association with AVSD.
4.3. Clinical Features and Evaluation
Most patients will have had surgery in childhood. The unrepaired adult may be asymptomatic or may present with congestive heart failure, exertional limitation, PAH and cyanosis, IE, or atrial flutter/fibrillation. Patients with partial AVSD are likely to become symptomatic at a younger age if significant left AV valve regurgitation is present.
4.3.1. Clinical Examination
Physical examination of the unoperated patient may show findings of an ASD, a VSD, AV valve regurgitation, LVOT obstruction, or PAH with cyanosis. A patient with severe PAH may have no murmur, a single loud second heart sound, and cyanosis/clubbing.
The typical repaired patient will have a normal examination apart from an apical systolic murmur if there is residual mitral regurgitation or subaortic obstruction. Subaortic obstruction may occur naturally in association with abnormal AV valve attachments or may be the consequence of surgery. In addition, the surgical repair may have created AV valve stenosis. Cyanosis should not be present in the absence of Eisenmenger syndrome or RV outflow obstruction.
The typical ECG shows superior left-axis deviation with a counterclockwise loop in the frontal plane. First-degree AV block may be present. Atrial flutter or fibrillation may develop in the older patient. Left atrial enlargement and LV hypertrophy may be present if there is significant left AV valve regurgitation. RV hypertrophy may predominate if there is PAH or associated RVOT obstruction.
4.3.3. Chest X-Ray
Cardiomegaly may be present due to dilation of the right or left AV heart chambers, depending on the degree and direction of AV valve regurgitation and the degree and level of left-to-right shunting. Increased pulmonary vascular markings are present when there is a significant left-to-right shunt. Pulmonary venous congestion may be seen when there is long-standing mitral regurgitation. In patients with PAH, a prominent main pulmonary artery segment and pruning of distal pulmonary vessels may be present.
In the patient with a partial and unrepaired AVSD, TTE is the primary imaging modality and should include demonstration of the borders of the primum ASD, a VSD (if present), the morphology and function of the AV valve, ventricular size and shunting, and SubAS (if present). In the patient with a complete and unrepaired AVSD, this will include the presence and size of the septal defect, the morphology and function of the common AV valve, and ventricular size and function. When the ventricular portion of the septal defect is large, the ventricular septum may be deficient apically and inferiorly. Pulmonary artery pressures (expected to be very high in complete AVSD) should be evaluated by measuring TR and pulmonary regurgitation jet velocity with simultaneous systemic blood pressure measurement. Evidence of subaortic obstruction, caused by AV valve attachments to the crest of the interventricular septum, should be sought by imaging and Doppler. In the postrepair patient, residua may include left AV valve dysfunction, SubAS, VSD patch leak, and PAH. It may be difficult to distinguish residual LV to right atrial shunt from TR with RV hypertension. The failure to distinguish these may result in erroneous diagnosis of PAH.
4.3.5. Magnetic Resonance Imaging
MRI may be useful to evaluate venous and arterial anatomy when associated lesions are suspected. Three-dimensional MRI is sometimes helpful in delineating leaflet morphology and outflow anatomy.
4.3.6. Recommendation for Heart Catheterization
1. Cardiac catheterization is reasonable to assess PAH and test vasoreactivity in patients with repaired or unrepaired AVSD. (Level of Evidence: B)
Heart catheterization has a limited role in the assessment of these patients unless noninvasive findings are equivocal. Evaluation of PAH and coronary anatomy may be needed when reoperation is being considered. Hemodynamic data may also be needed when noninvasive studies have not been able to provide this information.
4.3.7. Exercise Testing
Exercise testing may be used to objectively assess functional capacity.
4.4. Management Strategies
4.4.1. Medical Therapy
Most patients need no regular medication in the absence of specific problems. ACE inhibitors and/or diuretics may be used in patients with AV valve regurgitation and symptoms of chronic heart failure. Pulmonary vasodilation therapy may be indicated in patients with PAH and no significant left-to-right shunt who are deemed to be at high risk for surgical repair, but this should be approached with caution because of the potential for producing a significant right-to-left shunt.
4.4.2. Recommendations for Surgical Therapy
1. Surgeons with training and expertise in CHD should perform operations for AVSD. (Level of Evidence: C)
2. Surgical reoperation is recommended in adults with previously repaired AVSD with the following indications:
a. Left AV valve repair or replacement for regurgitation or stenosis that causes symptoms, atrial or ventricular arrhythmias, a progressive increase in LV dimensions, or deterioration of LV function. (Level of Evidence: B)
b. LVOT obstruction with a mean gradient greater than 50 mm Hg or peak instantaneous gradient greater than 70 mm Hg, or a gradient less than 50 mm Hg in association with significant mitral regurgitation or AR. (Level of Evidence: B)
c. Residual/recurrent ASD or VSD with significant left-to-right shunting (refer to Section 2, Atrial Septal Defect, and Section 3, Ventricular Septal Defect). (Level of Evidence: B)
Primary operation is rarely recommended for complete AVSD in adults because of pulmonary vascular obstructive disease. Unoperated partial or transitional AVSD, also known as partial or transitional AV canal, may not be identified until adulthood. Primary repair is generally recommended provided there is no fixed PAH.
Complete AVSD is usually repaired during infancy because of the risk of accelerated pulmonary vascular disease. Partial AVSD, also known as partial AV canal, is usually repaired in early childhood. The timing of repair of intermediate or transitional AVSD depends on the size of the VSD and the degree of shunting. Complete repair usually includes patch closure of the septal defect. Suture of the cleft in the left AV valve is dependent on leaflet morphology and surgical choice. Pulmonary artery banding of complete AVSD is rarely performed and is reserved for complex lesions.
Rerepair includes valve repair or replacement for left AV regurgitation or stenosis. LVOT obstruction is treated most commonly by resection of the fibrous stenosis/membrane, modified Konno procedure, or Konno-Rastan procedure. Suture or patch closure is performed for residual/recurrent ASD or VSD. A concomitant Maze procedure may be performed for intermittent or chronic atrial fibrillation/flutter. Management of patients should be in tertiary CHD centers or children's hospitals with experienced medical and surgical personnel.
4.5. Key Issues to Evaluate and Follow-Up
4.5.1. Key Postoperative Issues
Late complications may include left AV valve regurgitation and/or stenosis, LVOT obstruction with or without AR, and the development of heart block. Left AV valve regurgitation or stenosis requiring reoperation may occur in approximately 5% to 10% of patients. LVOT obstruction may occur in 5% of patients.
In the patient with prior repair, the onset of atrial arrhythmias should prompt a search for an underlying hemodynamic abnormality. Subaortic obstruction should be ruled out when there is a loud or harsh systolic murmur. Progressive left AV valve regurgitation may occur. The presence of an apical diastolic rumble without evidence of left-sided heart volume overload should prompt evaluation for left AV valve stenosis, particularly when there is evidence of PAH.
4.5.2. Evaluation and Follow-Up of the Repaired Patient
All patients should be assessed by and have periodic or regular follow-up with a cardiologist who has expertise in ACHD. The frequency, although typically annual, may be determined by the extent and degree of residual abnormalities. Appropriate imaging (2-dimensional and Doppler echocardiography in most patients) should be undertaken by staff trained in imaging of complex congenital heart defects and should include serial observation of AV valve function and evaluation of the LVOT. Periodic 24-hour ambulatory monitoring should be performed to assess rhythm abnormalities. Periodic cardiopulmonary testing may be helpful. Other testing should be arranged in response to clinical problems.
4.5.3. Electrophysiology Testing/Pacing Issues in Atrioventricular Septal Defects
In AVSD, the AV node and bundle of His are displaced inferiorly along the AV ring (182). This position puts the conduction system at risk for injury during surgical repair (169). Functional properties of these displaced conduction tissues can be suboptimal early in life (including the possibility of congenital complete heart block) and may worsen with age. For these reasons, the status of AV conduction must be monitored regularly with ECG and periodic Holter monitoring in adults with repaired or palliated AVSD.
4.5.4. Recommendations for Endocarditis Prophylaxis
1. Antibiotic prophylaxis before dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa is reasonable in patients with CHD with the highest risk for adverse outcome from IE, including those with the following indications:
b. Previous IE. (Level of Evidence: B)
c. Unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits. (Level of Evidence: B)
d. Completely repaired CHD with prosthetic materials, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure. (Level of Evidence: B)
e. Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibit endothelialization. (Level of Evidence: B)
2. It is reasonable to consider antibiotic prophylaxis against IE before vaginal delivery at the time of membrane rupture in select patients with the highest risk of adverse outcomes. This includes patients with the following indications:
b. Unrepaired and palliated cyanotic CHD, including surgically constructed palliative shunts and conduits. (Level of Evidence: C)
1. Prophylaxis against IE is not recommended for nondental procedures (such as esophagogastroduodenoscopy or colonoscopy) in the absence of active infection. (Level of Evidence: C)
4.6.1. Genetic Aspects
Trisomy 21, or Down syndrome, is commonly seen in association with AVSD. Such patients have a 50% risk of transmitting trisomy 21 and other genetic defects to their offspring. Reproductive counseling and discussion with the patient and those with medical power of attorney is warranted.
4.6.2. Recommendations for Pregnancy
1. All women with a history of AVSD should be evaluated before conception to ensure that there are no significant residual hemodynamic lesions that might complicate the management of pregnancy. (Level of Evidence: C)
2. The issue of pregnancy risk and preventive measures should be discussed with women with Down syndrome and their caregivers. (Level of Evidence: C)
Pregnancy is usually well tolerated by women who have had repair and who have no major residua, as well as by women with a primum defect who are functionally well. Pregnancy is not advised for women with severe PAH.
Most patients with uncomplicated, repaired AVSD can enjoy unlimited activity. Most will have subnormal exercise performance when measured objectively, but this typically does not impact on a normal lifestyle. Patients with important clinical problems (eg, severe left AV valve regurgitation, ongoing arrhythmias, or important LVOT obstruction) will often be advised to limit their activity. Advice regarding elite athletic activity should be individualized.
5. Patent Ductus Arteriosus
5.1. Definition and Associated Lesions
PDA is a persistent communication between the aorta and the pulmonary artery. It can be isolated or may be present in association with all forms of CHD. The most common associated lesions are VSDs or ASDs.
5.2. Presentation and Clinical Course
Unoperated patients may present with a heart murmur or symptoms caused by a large left-to-right shunt, including shortness of breath and easy fatigability. If the PDA is large and nonrestrictive, the patient may present with Eisenmenger physiology, including differential cyanosis and clubbing. Patients are at an increased risk of developing endarteritis, heart failure, and pulmonary vascular disease.
5.3. Recommendations for Evaluation of the Unoperated Patient
1. Definitive diagnosis of PDA should be based on visualization by imaging techniques and demonstrations of the shunting across the defect (with or without evidence of clinically significant LV volume overload). (Level of Evidence: C)
1. Diagnostic cardiac catheterization is not indicated for uncomplicated PDA with adequate noninvasive imaging. (Level of Evidence: B)
2. Maximal exercise testing is not recommended in PDA with significant PAH. (Level of Evidence: B)
The diagnostic workup for a patient with a suspected PDA is directed at defining the presence and size of the PDA, the functional effect of the shunt on the left atrium and left ventricle, the pulmonary circulation, and any associated lesions.
5.3.1. Clinical Examination
If the PDA is moderate or large, the presence of a continuous machinery-type murmur, heard best at the left infraclavicular area, and increased pulses are almost diagnostic. If PAH is present, only a systolic murmur may be heard. A wide pulse pressure is present when the PDA is large and there is a large left-to-right shunt. This must be distinguished from other causes of wide pulse pressure, such as aortic insufficiency and hyperthyroidism. In a patient with a large ductus and PAH, the oxygen saturation in the upper and lower extremities may be helpful in diagnosis of a large PDA with right-to-left shunt at the ductal level, because unoxygenated blood from the ductus enters the aorta distal to the left subclavian artery, causing cyanosis and often clubbing in the lower extremities.
The ECG may be normal if the ductus is small or may show left atrial enlargement and LV hypertrophy if there is a moderate left-to-right shunt. RV hypertrophy may be present if there is PAH.
Echocardiography with color Doppler in the parasternal short-axis view is diagnostic of a PDA. Measurement of the transpulmonary gradient across the ductus with continuous-wave Doppler can estimate the pulmonary artery pressure; however, in cases of significant elevation of PVR, echocardiography may not be diagnostic, and cardiac catheterization and angiography may be indicated.
5.3.4. Chest X-Ray
The chest x-ray may or may not show cardiomegaly and increased pulmonary vascular markings, depending on the size of the left-to-right shunt. There may be a prominent proximal pulmonary artery segment indicating elevated pulmonary artery pressure. An enlarged left atrium and left ventricle due to the left-to-right shunt may point to the presence of a significant PDA. One should look for calcification in the region of the ductus, because a calcified ductus is at an increased risk of rupture during surgical repair (284–286).
5.3.5. Cardiac Catheterization
During cardiac catheterization, it is important to evaluate the degree of shunt (in either direction), the PVR, and the reactivity of the vascular bed. Angiography can determine the size and shape of the ductus. If size and shape are suitable, the PDA can be treated in the catheterization laboratory.
5.3.6. Magnetic Resonance Imaging/Computed Tomography
Other diagnostic tests including CT scan or MRI of the chest usually are not necessary to diagnose a PDA.
5.4. Problems and Pitfalls
The differential diagnosis of a PDA on physical examination includes an aortopulmonary collateral, coronary arteriovenous fistula (CAVF), ruptured sinus of Valsalva, and a VSD with associated AR. It is important to differentiate between PDA and coronary AV fistulas, which may have similar findings. Echocardiography and/or angiography should be able to differentiate all of these conditions. In older adults, the calcified ductus poses a surgical risk, and catheter intervention should be the first option.
5.5. Management Strategies
The anatomy of the PDA in the adult is remarkable for the presence of calcification and general tissue friability in the area of the aortic isthmus and pulmonary artery, which makes surgical manipulation in the adult more hazardous than in the child. The need for surgical closure of a PDA in the adult is uncommon. When a PDA occurs in isolation, device closure is usually feasible. A PDA in combination with other intracardiac pathology may be closed at the time of cardiac operation. However, when cardiac operation is required for other reasons (eg, coronary artery bypass grafting), preoperative device closure of the PDA should be considered given the potential anatomic difficulties often encountered with the PDA in the adult population.
The primary surgical approach may be via thoracotomy or sternotomy, with or without cardiopulmonary bypass. The presence of ductal calcification in the adult can increase surgical risk. Ligation and division or patch closure from inside the main pulmonary artery or inside the aorta can be performed, depending on the presence or absence of ductal calcification. The majority of PDAs (greater than 95%) can be closed by operation, and early mortality is low. Recanalization is rare. Complications may include recurrent laryngeal nerve or phrenic nerve injury or thoracic duct injury.
5.5.1. Recommendations for Medical Therapy
1. Routine follow-up is recommended for patients with a small PDA without evidence of left-sided heart volume overload. Follow-up is recommended every 3 to 5 years for patients with a small PDA without evidence of left-heart volume overload. (Level of Evidence: C)
1. Endocarditis prophylaxis is not recommended for those with a repaired PDA without residual shunt. (Level of Evidence: C)
5.5.2. Recommendations for Closure of Patent Ductus Arteriosus
1. Closure of a PDA either percutaneously or surgically is indicated for the following:
a. Left atrial and/or LV enlargement or if PAH is present, or in the presence of net left-to-right shunting. (Level of Evidence: C)
b. Prior endarteritis. (Level of Evidence: C)
2. Consultation with ACHD interventional cardiologists is recommended before surgical closure is selected as the method of repair for patients with a calcified PDA. (Level of Evidence: C)
3. Surgical repair by a surgeon experienced in CHD surgery is recommended when:
a. The PDA is too large for device closure. (Level of Evidence: C)
b. Distorted ductal anatomy precludes device closure (eg, aneurysm or endarteritis). (82) (Level of Evidence: B)
1. It is reasonable to close an asymptomatic small PDA by catheter device. (Level of Evidence: C)
2. PDA closure is reasonable for patients with PAH with a net left-to-right shunt. (Level of Evidence: C)
1. PDA closure is not indicated for patients with PAH and net right-to-left shunt. (Level of Evidence: C)
5.5.3. Surgical/Interventional Therapy
Currently, the 2 approaches for PDA closure are surgical closure (285,286) and percutaneous catheter closure.(287–316) Surgical closure of PDA in the adult may pose some problems due to the friability and/or calcification of the ductus, atherosclerosis, and aneurysm formation, as well as the presence of other unrelated comorbid conditions, such as coronary atherosclerosis or renal disease, that may adversely affect the perioperative risk. Adults with PDA are better suited for percutaneous closure with either the occlusion device or coils because of its high success and few complications (317). If the PDA is associated with other conditions that require surgical correction, the ductus may be closed during the same operation, although percutaneous closure of the PDA before other cardiac surgery may decrease the risk of cardiopulmonary bypass.
5.6. Key Issues to Evaluate and Follow-Up
Adults with large PDAs are likely to have Eisenmenger physiology. Such patients require frequent follow-up to monitor their progress/deterioration. Problems associated with Eisenmenger physiology are discussed in Section 9, Pulmonary Hypertension/Eisenmenger Physiology.
Patients who have undergone surgical/PDA closure can be discharged safely from follow-up once complete closure of the ductus is documented by TTE. Antibiotic prophylaxis is discontinued 6 months after PDA closure. Follow-up approximately every 5 years for patients who received a device is recommended because of the lack of long-term data on device closure with the occlusion device.
6. Left-Sided Heart Obstructive Lesions: Aortic Valve Disease, Subvalvular and Supravalvular Aortic Stenosis, Associated Disorders of the Ascending Aorta, and Coarctation
LVOT obstruction syndromes include SubAS, valvular AS, SupraAS, and aortic coarctation (318). Obstruction can occur singly or at multiple levels, as an isolated lesion or in combination with septal defects or conotruncal anomalies.
BAV is one of the most common congenital cardiovascular malformations, with an estimated incidence of 1% to 2% of the population. The prevalence of AS is harder to calculate because, unlike many other congenital heart lesions, a BAV may develop significant obstruction or regurgitation after midlife, with a peak age range for surgical intervention between 60 and 80 years (275,319). There is male preponderance for AS. A BAV may be inherited, and family clusters have been studied (319,320).
BAV abnormalities arise from abnormal cusp formation during valvulogenesis, commonly with fusion between 2 cusps, forming 1 smaller and 1 larger cusp. Variants range from a nearly trileaflet aortic valve with cusp inequality to a unicuspid and dysplastic valve. A BAV can be predominately obstructive or regurgitant, depending on the degree of commissural fusion. The valve may dome in systole, but a dysplastic valve is poorly mobile and does not dome. In many patients with BAV, the histology of the aortic wall is similar to Marfan syndrome, with abnormalities of smooth muscle, extracellular matrix, elastin, and collagen (321–323).
In general, the severity of valvular AS in adults is graded mild, moderate, or severe on the basis of the valve area and jet velocity across the aortic valve as measured by Doppler echocardiography. Degrees of AS are defined in the 2006 ACC/AHA valvular heart disease guidelines as mild (a valve area greater than 1.5 cm2, mean gradient less than 25 mm Hg, or jet velocity less than 3.0 ms), moderate (valve area 1.0 to 1.5 cm2, mean gradient 25 to 40 mm Hg, or jet velocity 3.0 to 4.0 ms), or severe (valve area less than 1.0 cm2, mean gradient greater than 40 mm Hg, or jet velocity greater than 4.0 m per s). Not all experts agree with these specifics, but these values provide a frame of reference in discussing severity of AS. In adolescents and young adults less than 30 years of age, AS severity is often reported on the basis of the mean gradient measured by Doppler echocardiography (112).
6.2. Associated Lesions
Abnormalities associated with BAV disease include SubAS, parachute mitral valve, VSD, PDA, or coarctation of the aorta with varying degrees of arch hypoplasia. A left-dominant coronary artery system is more frequent with BAV (324). Turner syndrome may be associated with AS in addition to aortic coarctation. The presence of multiple levels of left-sided heart obstructions (eg, SubAS, BAV, AS, coarctation, parachute mitral valve, or supramitral ring) is termed Shones syndrome. Patients presenting in childhood with LVOT obstruction generally have more complex or severe disease than those found to have BAV in adult life. BAV disease can be associated with progressive dilation of the aortic root, aortic aneurysm, and even rupture or dissection; intrinsic abnormalities of aortic wall elastin may result in ascending aortic dilation even with a normally functioning aortic valve.
6.3. Clinical Course (Unrepaired)
In adults, in the absence of superimposed acute endocarditis, BAV disease is usually a slowly progressive disorder with gradual development and progression of AS or AR (325,326). Asymmetrical flow patterns with turbulence subject the BAV to abnormally high stresses, which leads to thickening, calcification, and progressive stenosis or leaflet retraction and AR (42).
Evidence of echocardiographic “sclerosis” may be seen as early as the second decade, and calcification is often evident by the fourth decade (327). Most patients older than 45 years have significant BAV calcification and/or thickening, which often relates to hemodynamic severity. The presence of risk factors, such as hyperlipidemia, appears to be associated with progression of BAV stenosis (328,329).
Progressive AS is the most common complication of BAV, and many patients will require valve surgery or percutaneous valvuloplasty, with only one third or fewer remaining functionally normal by the fifth decade of life (330). The rate of progression of valvular AS is faster in those valves with anteroposterior-oriented line of closure and in those with greater closure-line eccentricity (327). In such patients, the BAV systolic peak pressure gradient increased 27 mm Hg per decade. Concomitant AR can also accelerate progression of valvular AS (327).
In addition to ascending aorta aneurysms and dissections, there can be familial aortocervicocephalic arterial dissections in conjunction with BAV disease (331). In a longitudinal study of the long-term outcomes of 622 adults with asymptomatic but hemodynamically severe AS at study inception, most developed symptoms within 5 years, and sudden death occurred at a rate of 1% per year (332).
Gradual progression of AR may occur in BAV due to several mechanisms (ie, leaflet prolapse or fibrosis and leaflet edge retraction or aortic root dilatation). Abrupt AR occurs owing to IE with leaflet destruction or perforation or, rarely, owing to loss of suspension of a leaflet due to intimal aortic dissection. Rarely, a flail aortic valve occurs spontaneously as a result of rupture of tenuous support at a raphe. Aortic dissection is well described in BAV, particularly if associated with aortic coarctation (333–335). The risk of aortic dissection in BAV is estimated at 5 to 9 times that of the general population (334,336).
6.4. Recommendations for Evaluation of the Unoperated Patient
Recommendations and guidelines concerning AS, BAV, and AR in the adult patient are also discussed in the 2006 valvular heart disease guidelines (112).
1. Primary imaging and hemodynamic assessment of AS and aortic valve disease are recommended by echocardiography-Doppler to evaluate the presence and severity of AS or AR; LV size, function, and mass; and dimensions and anatomy of the ascending aorta and associated lesions. (Level of Evidence: B)
2. Echocardiography is recommended for reevaluation of patients with AS who experience a change in signs or symptoms and for assessment of changes in AS hemodynamics during pregnancy. (Level of Evidence: B)
3. In asymptomatic adolescents and young adults, echocardiography-Doppler is recommended yearly for AS with a mean Doppler gradient greater than 30 mm Hg or peak instantaneous gradient greater than 50 mm Hg and every 2 years for patients with lesser gradients. (Level of Evidence: C)
4. Cardiac catheterization is recommended when noninvasive measurements are inconclusive or discordant with clinical signs. (Level of Evidence: C)
5. Coronary angiography is recommended before aortic valve surgery for coronary angiography in adults at risk for coronary artery disease. (Level of Evidence: B)
6. Coronary angiography is recommended before a Ross procedure if noninvasive imaging of the coronary arteries is inadequate. (Level of Evidence: C)
7. A yearly ECG is recommended in young adults less than 30 years of age with mean Doppler gradients greater than 30 mm Hg or peak Doppler gradients greater than 50 mm Hg. (Level of Evidence: C)
8. An ECG is recommended every other year in young adults less than 30 years of age with mean Doppler gradients less than 30 mm Hg or peak Doppler gradients less than 50 mm Hg. (Level of Evidence: C)
1. In asymptomatic young adults less than 30 years of age, exercise stress testing is reasonable to determine exercise capability, symptoms, and blood pressure response. (Level of Evidence: C)
2. Exercise stress testing is reasonable for patients with a mean Doppler gradient greater than 30 mm Hg or peak Doppler gradient greater than 50 mm Hg if the patient is interested in athletic participation or if clinical findings differ from noninvasive measurements. (Level of Evidence: C)
3. Exercise stress testing is reasonable for the evaluation of an asymptomatic young adult with a mean Doppler gradient greater than 40 mm Hg or a peak Doppler gradient greater than 64 mm Hg or when the patient anticipates athletic participation or pregnancy. (Level of Evidence: C)
4. Dobutamine stress testing can be beneficial in the evaluation of a mild aortic valve gradient in the face of low LV ejection fraction and reduced cardiac output. (Level of Evidence: C)
5. MRI/CT can be beneficial to add important information about the anatomy of the thoracic aorta. (Level of Evidence: C)
6. Exercise stress testing can be useful to evaluate blood pressure response or elicit exercise-induced symptoms in asymptomatic older adults with AS. (Level of Evidence: B)
1. Magnetic resonance angiography may be beneficial in quantifying AR when other data are ambiguous or borderline. (Level of Evidence: C)
1. Exercise stress testing should not be performed in symptomatic patients with AS or those with repolarization abnormality on ECG or systolic dysfunction on echocardiography. (Level of Evidence: C)
6.4.1. Clinical Examination
A delayed carotid upstroke with decreased volume is usual with severe AS. A systolic thrill may be present in the suprasternal notch or at the upper right sternal border. Palpation of the LV impulse may reveal a prominent and sustained apical impulse. A systolic ejection sound is usually present (until the fourth decade, after which calcification may restrict mobility of the cusps), usually loudest at the apex but also radiating to the base. An apical crescendo-decrescendo systolic murmur of AS radiating to the upper right sternal border and over the carotids is characteristic.
In patients with moderate to severe AR and LV enlargement, the apical impulse is displaced laterally and is hyperdynamic. An early diastolic high-pitched murmur of AR is usually loudest along the mid-left sternal border. An AR murmur that is louder at the right sternal border indicates aortic root dilatation.
An ECG may reveal QRS voltage of LV hypertrophy, a left atrial abnormality pattern, and/or ST-T repolarization changes.
6.4.3. Chest X-Ray
The chest x-ray may reveal a prominent right-sided heart–border silhouette of the ascending aorta (if dilated), calcification in the aortic valve (if calcification is present), and a left-sided heart–border silhouette of LV hypertrophy/enlargement.
The echocardiographic assessment should include valve anatomy and motion; aortic root anatomy and dimensions; LV mass, size/volumes, and function (both systolic and diastolic); and the presence or absence of AR. For AS, the continuity equation should be used in adults to calculate aortic valve area (cm2), preferably indexed to body surface area (cm2 per m2).
The peak instantaneous aortic valve gradient alone may overestimate the severity of AS. The mean Doppler gradient may be more reflective of the peak-to-peak gradient as measured at catheterization that is classically used for clinical decision making. Several different methods for quantification of AR should be used, including pressure half-time, jet width, and degree of proximal descending aortic diastolic flow reversal (337).
6.4.5. Magnetic Resonance Imaging/Computed Tomography
MRI/magnetic resonance angiography or CT is valuable in evaluating anatomy of the entire aorta to quantify AR in borderline cases.
6.4.6. Stress Testing
Selective use of exercise stress testing to assess blood pressure and heart rate response, rhythm disorders, and ST-T segment changes may be warranted. The prognostic value of exercise-induced ST depression and T-wave inversion is age dependent, because 80% of adults with AS will have ST depression without prognostic significance. On the other hand, ST-T changes in an adolescent or young adult with exercise may be indications for intervention. The use of stress echocardiography to assess aortic valve area and gradient, LV ejection fraction, and LV volume response may be helpful. The selective use of dobutamine stress echocardiographic studies has been valuable in low-gradient AS with low LV ejection fractions, a situation that is uncommon in adolescents with AS or AR but may be present in older adults with concomitant myocardial or coronary artery disease.
6.4.7. Cardiac Catheterization
Diagnostic catheterization is used selectively when the clinical and echocardiography-Doppler data are incongruent or as a prelude to catheter or surgical intervention. In many laboratories, it is used primarily for the assessment of preoperative coronary anatomy in males greater than 35 years of age or those with other risk factors for atherosclerosis.
6.5. Problems and Pitfalls
Problems and pitfalls regarding BAV stenosis include the following:
• The click murmur of a BAV may be misdiagnosed as mitral valve prolapse.
• A systolic murmur may be thought to be “benign” because an ejection click is not recognized.
• To quantify the severity of valvular AS by echocardiography-Doppler, mean gradient and aortic valve area should be used rather than relying only on peak systolic gradient, which may overestimate the severity of stenosis. The aortic valve area should be indexed to body surface area to correct for different body sizes and habitus.
• Progressive aortic dilatation may occur in patients with BAV even in the absence of significant AS or AR.
• In the presence of increased LV dimensions and normal wall thickness, an increased LV mass is present. LV mass calculations are needed and should be indexed to body surface area (338).
6.6. Management Strategies for Left Ventricular Outflow Tract Obstruction and Associated Lesions
6.6.1. Recommendations for Medical Therapy
1. It is reasonable to treat systemic hypertension in patients with AS while monitoring diastolic blood pressure to avoid reducing coronary perfusion. (Level of Evidence: C)
2. It is reasonable to administer beta blockers in patients with BAV and aortic root dilatation. (Level of Evidence: C)
3. It is reasonable to use long-term vasodilator therapy in patients with AR and systemic hypertension while carefully monitoring diastolic blood pressure to avoid reducing coronary perfusion. (Level of Evidence: C)
1. It may be reasonable to treat patients with BAV and risk factors for atherosclerosis with statins with the aim of slowing down degenerative changes in the aortic valve and preventing atherosclerosis. (Level of Evidence: C)
1. Vasodilator therapy is not indicated for long-term therapy in AR for the following:
a. The asymptomatic patient with only mild to moderate AR and normal LV function. (Level of Evidence: B)
b. The asymptomatic patient with LV systolic dysfunction who is otherwise a candidate for AVR. (Level of Evidence: B)
c. The asymptomatic patient with either LV systolic function or mild to moderate LV diastolic dysfunction who is otherwise a candidate for AVR. (Level of Evidence: C)
There are currently no established medical treatments proven to alter the natural history or halt the progression of stenosis in BAV disease (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information). Beta blockers may be administered to delay or prevent aortic root dilatation or progression, but benefit has only been validated in patients with Marfan syndrome or acute aortic dissections. Judicious afterload reduction in patients with hypertension to reduce systolic blood pressure and lower LV wall tension may delay onset of LV dilatation or dysfunction but should be balanced against the risk of reducing diastolic coronary perfusion. There is no clear evidence that afterload reduction decreases the volume of AR or reduces the need for AVR (339). Multimodality molecular imaging has identified proteolytic and osteogenic activity in early aortic valve disease, a precursor to atherosclerotic and calcific degenerative AS (340). Thus, statins may slow the progression of acquired or calcific degenerative AS and probably have a role in treatment of BAV disease early in the process, before significant calcification and AS or AR have developed (341). Although no clinical trials have confirmed the benefits of statins in BAV disease, it appears reasonable to treat those patients who have risk factors for atherosclerosis.
6.6.2. Catheter and Surgical Intervention
In adults with AS, intervention for significant disease usually involves AVR or Ross repair; however, selected adolescents and young adults may benefit from percutaneous balloon valvuloplasty. This technique should be performed at centers with appropriate experience and expertise (112).
18.104.22.168. Recommendations for Catheter Interventions for Adults With Valvular Aortic Stenosis
1. In young adults and others without significantly calcified aortic valves and no AR, aortic balloon valvotomy is indicated in the following patients:
a. Those with symptoms of angina, syncope, dyspnea on exertion, and peak-to-peak gradients at catheterization greater than 50 mm Hg. (Level of Evidence: C)
b. Asymptomatic adolescents or young adults who demonstrate ST or T-wave abnormalities in the left precordial leads on ECG at rest or with exercise and a peak-to-peak catheter gradient greater than 60 mm Hg. (Level of Evidence: C)
1. Aortic balloon valvotomy is reasonable in the asymptomatic adolescent or young adult with AS and a peak-to-peak gradient on catheterization greater than 50 mm Hg when the patient is interested in playing competitive sports or becoming pregnant. (Level of Evidence: C)
1. Aortic balloon valvotomy may be considered as a bridge to surgery in hemodynamically unstable adults with AS, adults at high risk for AVR, or when AVR cannot be performed secondary to significant comorbidities. (Level of Evidence: C)
1. In older adults, aortic balloon valvotomy is not recommended as an alternative to AVR, although certain younger patients may be an exception and should be referred to a center with experience in aortic balloon valvuloplasties. (Level of Evidence: B)
2. In asymptomatic adolescents and young adults, aortic balloon valvotomy should not be performed with a peak-to-peak gradient less than 40 mm Hg without symptoms or ECG changes. (Level of Evidence: B)
When valvular AS is secondary to bicuspid commissural fusion, especially in young adults, the potential exists for successful balloon dilation with gradient reduction and extended freedom from reintervention (320). Increasing calcification, with concomitantly increasing transvalvular gradient with increasing patient age, limits results in older adults, in whom AVR is the intervention of choice (320). Criteria for intervention vary, with typical indications including a valve area less than or equal to 0.45 cm2 per m2 (if not indexed, 0.8 cm2 for an average-sized adult with a height of 1.7 m2), especially in the setting of symptoms of dyspnea, angina, or syncope or with worsening ventricular function. Balloon valvuloplasty may be considered in younger patients in whom there is a need to have augmented cardiac output, such as those with a desire to become pregnant or to participate in vigorous sports. When balloon valvuloplasty is indicated, patients should be referred to a center experienced in the procedure.
22.214.171.124. Recommendations for Aortic Valve Repair/Replacement and Aortic Root Replacement
1. Aortic valvuloplasty, AVR, or Ross repair is indicated in patients with severe AS or chronic severe AR while they undergo coronary artery bypass grafting, surgery on the aorta, or surgery on other heart valves. (Level of Evidence: C)
2. AVR is indicated for patients with severe AS and LV dysfunction (LV ejection fraction less than 50%). (Level of Evidence: C)
3. AVR is indicated in adolescents or young adults with severe AR who have:
a. Development of symptoms. (Level of Evidence: C)
b. Development of persistent LV dysfunction (LV ejection fraction less than 50%) or progressive LV dilatation (LV end-diastolic diameter 4 standard deviations above normal). (Level of Evidence: C)
4. Surgery to repair or replace the ascending aorta in a patient with a BAV is recommended when the ascending aorta diameter is 5.0 cm or more or when there is progressive dilatation at a rate greater than or equal to 5 mm per year. (112) (Level of Evidence: B)
1. AVR is reasonable for asymptomatic patients with severe AR and normal systolic function (ejection fraction greater than 50%) but with severe LV dilatation (LV end-diastolic diameter greater than 75 mm or end-systolic dimension greater than 55 mm⁎). (Level of Evidence: B)
2. Surgical aortic valve repair or replacement is reasonable in patients with moderate AS undergoing coronary artery bypass grafting or other cardiac or aortic root surgery. (Level of Evidence: B)
1. AVR may be considered for asymptomatic patients with any of the following indications:
a. Severe AS and abnormal response to exercise. (Level of Evidence: C)
b. Evidence of rapid progression of AS or AR. (Level of Evidence: C)
c. Mild AS while undergoing coronary artery bypass grafting or other cardiac surgery and evidence of a calcific aortic valve. (Level of Evidence: C)
d. Extremely severe AS (aortic valve area less than 0.6 cm and/or mean Doppler systolic AV gradient greater than 60 mm Hg) in an otherwise good operative candidate. (Level of Evidence: C)
e. Moderate AR undergoing coronary artery bypass grafting or other cardiac surgery. (Level of Evidence: C)
f. Severe AR with rapidly progressive LV dilation when the degree of LV dilation exceeds an end-diastolic dimension of 70 mm or end-systolic dimension of 50 mm, with declining exercise tolerance, or with abnormal hemodynamic responses to exercise. (Level of Evidence: C)
2. Surgical repair may be considered in adults with AS or AR and concomitant ascending aortic dilatation (ascending aorta diameter greater than 4.5 cm) coexisting with AS or AR. (Level of Evidence: B)
3. Early surgical repair may be considered in adults with the following indications:
a. AS and a progressive increase in ascending aortic size. (Level of Evidence: C)
b. Mild AR if valve-sparing aortic root replacement is being considered. (Level of Evidence: C)
1. AVR is not useful for prevention of sudden death in asymptomatic adults with AS who have none of the findings listed under the Class IIa/IIb indications. (Level of Evidence: B)
2. AVR is not indicated in asymptomatic patients with AR who have normal LV size and function. (Level of Evidence: B)
In adults, surgical AVR or Ross procedure is the primary intervention for aortic valve disease. Complications related to Shones syndrome and multiple levels of obstruction warrant referral to a surgeon with experience in ACHD. Congenital heart surgeons should perform complex operations that involve LVOT obstruction (eg, modified Konno or Konno procedure), and management of these patients should be in a tertiary center with experienced ACHD medical and surgical personnel.
In BAV disease, there is no consensus regarding the specific diameter of the ascending aorta for which replacement is indicated, but greater than or equal to 5 cm has been suggested by some (112). Whether aortic root replacement or wrapping is optimal in such patients is a matter of debate; results of AVR in CHD have an acceptable medium-term result (342). There has been concern about the stability of neoaortic root sizes with the Ross procedure for BAV with a dilated aortic root (322), in part because of data on the free-standing aortic root technique, after which progressive root enlargement and neo-AR have been noted (340). Simon-Kupilik et al (343) reported that by 7 years after the Ross procedure, only 45% of patients were free of neoaortic autograft dilatation, but 90% had an increase in autograft root dimensions greater than 25%. However, dilatation did not always necessitate reoperation for aneurysm formation or increasing AR (343), and the use of a subcoronary Ross procedure results in stable root dimensions (344,345).
6.7. Recommendations for Key Issues to Evaluate and Follow-Up
1. Lifelong cardiology follow-up is recommended for all patients with aortic valve disease (AS or AR) (operated or unoperated; refer to Section 6.4, Recommendations for Evaluation of the Unoperated Patient). (Level of Evidence: A)
2. Serial imaging assessment of aortic root anatomy is recommended for all patients with BAV, regardless of severity. The frequency of imaging would depend on the size of the aorta at initial assessment: if less than 40 mm, it should be reimaged approximately every 2 years; if greater than or equal to 40 mm, it should be reimaged yearly or more often as progression of root dilation warrants or whenever there is a change in clinical symptoms or findings. (Level of Evidence: B)
3. Prepregnancy counseling is recommended for women with AS who are contemplating pregnancy. (Level of Evidence: B)
4. Patient referral to a pediatric cardiologist experienced in fetal echocardiography is indicated in the second trimester of pregnancy to search for cardiac defects in the fetus. (Level of Evidence: C)
5. Women with BAV and ascending aorta diameter greater than 4.5 cm should be counseled about the high risks of pregnancy. (Level of Evidence: C)
6. Patients with moderate to severe AS should be counseled against participation in competitive athletics and strenuous isometric exercise. (Level of Evidence: B)
7. Echocardiographic screening for the presence of BAV is recommended for first-degree relatives of patients with BAV. (Level of Evidence: B)
Progressive or recurrent AS, AR, or aortic enlargement may occur in the presence of a BAV. Patients with or without intervention should be followed up at least yearly for symptoms and findings of progressive AS/AR ventricular dysfunction and arrhythmia. This includes resting and stress ECGs to look for ischemic changes or arrhythmia; echocardiography-Doppler to monitor LV size/volume and systolic and diastolic function, aortic valve function, and aortic root size and anatomy; and 24-hour ambulatory ECG monitoring.
With or without intervention, both AS and AR are progressive lesions that may ultimately require surgical intervention. Prosthetic valve complications include endocarditis, thrombosis, periprosthetic regurgitation with or without hemolysis, and obstruction related to pannus in growth. Patients who undergo the Ross procedure (placement of the native pulmonary valve in the aortic position and pulmonary or aortic homograft replacement of the pulmonary valve) are at risk of developing autograft dilatation with progressive neo-AR, right-sided pulmonary homograft obstruction and/or regurgitation, and occasionally myocardial ischemia and/or infarct related to proximal coronary artery obstruction or kinking. Patients who undergo the Bentall procedure (aortic root replacement with a composite valve and graft with coronary reimplantation) are also at risk for proximal coronary obstruction.
Congenital AS with a long-standing significant gradient can be associated with ventricular arrhythmias in adulthood, including the small possibility of sudden cardiac death (346). Patients should be monitored carefully for symptoms and should have regular ECGs, plus periodic ambulatory rhythm monitoring, to assist in early detection of arrhythmias (104,347).
Most pregnancies with congenital AS are uncomplicated, but in those with severe AS, morbidity is higher, although deaths are still rare (348,349). Prepregnancy counseling is recommended. Referral to a fetal cardiologist is indicated in the second trimester because there is an increased risk of transmitting CHD to offspring. Delivery in all but the mildest of cases may be best accomplished at centers experienced with high-risk heart disease. Vaginal delivery is generally preferable to cesarean delivery except in the presence of obstetric contraindications or severe cardiac situations, such as aortic aneurysm, dissection, or critical AS, or in women who are undergoing anticoagulation (because of the risks of intracranial bleeding in the newborn). Delivery may be performed under controlled circumstances at approximately 38 weeks (provided fetal lung maturity is deemed sufficient) with appropriate monitoring of maternal heart rate, blood pressure, and fetal monitoring. Even though the 2007 AHA Scientific Statement on Prevention of Infective Endocarditis does not recommend routine prophylaxis for vaginal delivery or cesarean section, many obstetricians administer antibiotics at the time of rupture of membranes for women with aortic valve disease (74) (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information). Prepregnancy or prenatal evaluation and counseling in women with congenital aortic valve disease is essential to explore options and manage risks. The role of balloon valvuloplasty in the palliation of symptomatic pregnant women with AS requires further study, but it may be applied successfully if symptoms are refractory to medical therapy (348,350). There is no evidence that pregnancy accelerates progression of congenital AS or AR. In some cases, the drop in systemic vascular resistance that accompanies pregnancy may reduce the regurgitant fraction in AR (351).
Patients with moderate to severe AS who participate in competitive athletics risk sudden cardiac death, likely from arrhythmias; therefore, they should be strongly counseled against competitive athletics and strenuous isometric exercise. Patients with aortopathy should be similarly counseled about the risks of chest injury. Exercise and athletics have been addressed in the report of Task Force 2 on CHD of the 36th Bethesda Conference (49).
6.8. Isolated Subaortic Stenosis
SubAS refers to a discrete fibrous ring or fibromuscular narrowing and is distinct from genetic hypertrophic cardiomyopathy with dynamic LVOT obstruction. Often, the subaortic fibrous ring may extend onto the anterior mitral leaflet. On occasion, accessory mitral tissue or anomalous chords may cause SubAS. SubAS is usually a solitary congenital defect but may be superimposed on other congenital heart defects (eg, VSD) or acquired under certain circumstances (eg, after VSD patching). Although the obstruction is usually fixed, a secondary dynamic component may develop due to myocardial hypertrophy and dynamic LV ejection.
The prevalence of discrete SubAS among ACHD patients has been reported to be 6.5% (352), with a male preponderance of 2:1. In some cases, such as Shones syndrome, SubAS may be familial.
6.8.2. Associated Lesions
SubAS may occur as an associated defect with VSDs, AVSD, or conotruncal anomalies and may develop after patch closure of a perimembranous or malaligned VSD or AVSD (353).
6.8.3. Clinical Course With/Without Previous Intervention
The course of SubAS is often progressive. The unrepaired history includes progressive aortic valve damage, ventricular dysfunction, IE, and sudden cardiac death. The dominant feature may be obstruction or AR (352,354,355). AR occurs in more than 50% of those with SubAS. Once the peak Doppler gradient across the SubAS is more than 30 mm Hg, and if the membrane is immediately adjacent to the aortic valve or there is extension of the membrane onto the mitral valve, LVOT obstruction is likely to be progressive (354). Once the peak instantaneous Doppler LVOT gradient reaches 50 mm Hg or more, there is increased risk for moderate or severe AR (354). Patients are at risk for endocarditis, which will contribute to worsening AR (356).
6.8.4. Clinical Features and Evaluation
126.96.36.199. Clinical Examination
The murmur of SubAS is crescendo-decrescendo and is present at the apex and over the left parasternal precordium. Transmission into the carotids is inconsistent. In contrast to valvular AS, no ejection click is present. In some patients, a thrill may be present. A high-frequency early diastolic murmur of AR may be heard along the left sternal border.
The ECG may be normal if there is no significant AS or AR or may show varying degrees of LV hypertrophy and secondary repolarization abnormalities.
188.8.131.52. Chest X-Ray
The chest x-ray is usually normal unless the development of significant AR results in LV dilatation and/or the ascending aorta.
Transthoracic 2-dimensional echocardiography-Doppler is the initial diagnostic method of choice to precisely characterize LV outflow anatomy, severity of subaortic gradient, associated aortic valve abnormality, degree of AR, diameter of the ascending aorta, and mitral valve involvement, as well as to assess LV hypertrophy and function (systolic and diastolic) in patients suspected of having SubAS. TEE may add valuable anatomic detail, both preoperatively and intraoperatively. Three-dimensional echocardiography may be particularly helpful in demonstrating complex LV outflow anatomy.
6.8.5. Diagnostic Cardiac Catheterization
Noninvasive imaging is usually sufficient for evaluation and monitoring of patients with SubAS. Cardiac catheterization may be indicated when SubAS is associated with other lesions. Accurate measurement of the subvalvular gradient necessitates the use of end-hole or micromanometer-tipped catheters. LV angiography is often unreliable for diagnosis of a discrete subaortic membrane, although carefully angulated views may reveal the membrane.
6.8.6. Problems and Pitfalls
The findings of a discrete fibrous subaortic ring may be subtle on TTE, unless there are good acoustical windows that allow transducer positions perpendicular to the membrane and the LVOT obstruction is examined carefully with color flow Doppler. The degree of SubAS may be underestimated or overestimated in the presence of a VSD, depending on whether the VSD is proximal or distal to the subaortic obstruction.
6.8.7. Management Strategies
184.108.40.206. Medical Therapy
There is no specific medical therapy for SubAS, except endocarditis prophylaxis when there is a prior history of endocarditis (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).
220.127.116.11. Recommendations for Surgical Intervention
1. Surgical intervention is recommended for patients with SubAS and a peak instantaneous gradient of 50 mm Hg or a mean gradient of 30 mm Hg on echocardiography-Doppler. (Level of Evidence: C)
2. Surgical intervention is recommended for SubAS with less than a 50-mm Hg peak or less than a 30-mm Hg mean gradient and progressive AR and an LV dimension at end-systolic diameter of 50 mm or more or LV ejection fraction less than 55%. (Level of Evidence: C)
1. Surgical resection may be considered in patients with a mean gradient of 30 mm Hg, but careful follow-up is required to detect progression of stenosis or AR. (Level of Evidence: C)
2. Surgical resection may be considered for patients with less than a 50-mm Hg peak gradient or less than a 30-mm Hg mean gradient in the following situations:
a. When LV hypertrophy is present. (Level of Evidence: C)
b. When pregnancy is being planned. (Level of Evidence: C)
c. When the patient plans to engage in strenuous/competitive sports. (Level of Evidence: C)
1. Surgical intervention is not recommended to prevent AR for patients with SubAS if the patient has trivial LVOT obstruction or trivial to mild AR. (Level of Evidence: C)
Surgical intervention should be recommended for patients with SubAS when the peak instantaneous echocardiographic gradient is greater than 50 mm Hg, the mean gradient is greater than 30 mm Hg, or catheter measurement of the resting peak-to-peak gradient is greater than 50 mm Hg. Patients with lesser degrees of obstruction may be considered for surgery in the presence of LV systolic dysfunction or significant aortic valve regurgitation or if the patient desires to become pregnant or to participate in active sports.
Patients with peak gradients less than 50 mm Hg and symptoms of breathlessness or fatigability should be investigated with exercise Doppler to determine whether the gradient increases with exertion. The presence of LV systolic dysfunction or a VSD proximal to the SubAS may result in underestimation of obstruction. The value of surgical resection for the sole purpose of preventing progressive AR in patients without other criteria for surgical intervention has not been determined and is an issue about which there is no clear consensus.
Surgical repair of discrete SubAS usually involves circumferential resection of the fibrous ring and some degree of resection of the muscular base along the left septal surface. Potential operative complications include injury to the aortic or mitral valves, complete heart block, or creation of a VSD. Patients with associated AR often undergo valve repair at the time of subaortic resection. Fibromuscular or tunnel-type SubAS is more difficult to palliate surgically and usually involves a more aggressive septal resection and sometimes mitral valve replacement. Patients with SubAS due to severe long-segment LVOT obstruction may require a Konno procedure, which involves an extensive patch augmentation of the LV outflow area to the aortic annulus.
Postoperative complications may include damage to the aortic or mitral valve, heart block, iatrogenic VSD, and IE. SubAS may recur after surgical repair; repair of SubAS in children does not necessarily prevent AR development in adults (352,357). However, data exist to suggest that surgical resection of fixed SubAS before the development of a more than 40-mm Hg LVOT gradient may prevent reoperation and secondary progressive aortic valve disease (358). Although catheter palliation has been performed in some centers on an experimental basis, its efficacy has not been demonstrated (359).
6.8.8. Recommendations for Key Issues to Evaluate and Follow-Up
1. Lifelong cardiology follow-up, including evaluation by and/or consultation with a cardiologist with expertise in ACHD, is recommended for all patients with SubAS, repaired or not. (Level of Evidence: C)
2. The unoperated asymptomatic adult with stable LVOT obstruction due to SubAS and a mean gradient less than 30 mm Hg without LV hypertrophy or significant AR should be monitored at yearly intervals for increasing obstruction, the development or progression of AR, and the evaluation of systolic and diastolic LV function. (Level of Evidence: B)
1. Stress testing to determine exercise capability, symptoms, ECG changes or arrhythmias, or increase in LVOT gradient is reasonable in the presence of otherwise equivocal indications for intervention. (Level of Evidence: C)
Progressive and/or recurrent obstruction and progressive AR may occur in patients with or without intervention. Recurrent obstruction is frequent after resection of SubAS and occurs at a rate of approximately 20% over 10 years. In addition, AR may occur despite resection of the subaortic membrane.
6.8.9. Special Issues
Refer to Section 6.7.1, Reproduction.
18.104.22.168. Exercise and Athletics
Refer to Section 6.7.2, Activity/Exercise.
6.9. Supravalvular Aortic Stenosis
SupraAS is a fixed obstruction that arises from just above the sinus of Valsalva and extends a variable distance along the aorta. The origin of the coronary arteries is usually proximal to the obstruction, which subjects them to high systolic pressure and limited diastolic flow. There may be partial or complete ostial obstruction of the coronary arteries, ectasia, or aneurysm of the coronary arteries (360). Pathological specimens with diffuse or focal intimal and medial fibrosis, hyperplasia, dysplasia, adventitial fibroelastosis, and occasional intramedial dissection have been reported in children and more commonly in adults (361–363). This may produce significant coronary insufficiency and early onset of coronary artery disease in adult life.
6.9.2. Associated Lesions
SupraAS is commonly seen in Williams syndrome and can be associated with hypoplasia of the entire aorta, renal artery stenosis, stenoses of other major aortic branches, and long-segment peripheral pulmonary artery stenosis. Williams syndrome, an autosomal dominant disorder due to an elastin gene mutation, is associated with abnormal (elfin) facies, cognitive and behavioral disorders, and joint abnormalities. Familial non-Williams SubAS is also associated with branch pulmonary artery stenosis and hypoplasia, as well as hypoplastic descending aorta and renal artery stenosis.
6.9.3. Clinical Course (Unrepaired)
Most patients with SupraAS will be followed up from childhood and may present in adult life with symptoms due to significant outflow obstruction, systemic hypertension, or ischemia. Clinical presentation with ischemic symptomatology referable to insufficient coronary artery flow has been reported due to either anatomic obstruction or myocardial hypertrophy that limits nonepicardial coronary flow (364).
6.10. Recommendations for Evaluation of the Unoperated Patient
1. TTE and/or TEE with Doppler and either MRI or CT should be performed to assess the anatomy of the LVOT, the ascending aorta, coronary artery anatomy and flow, and main and branch pulmonary artery anatomy and flow. (Level of Evidence: C)
2. Assessment of anatomy and flow in the proximal renal arteries is recommended in ACHD patients with SupraAS. (Level of Evidence: C)
3. Assessment of systolic and diastolic ventricular function is recommended in ACHD patients with SupraAS. (Level of Evidence: C)
4. Assessment of aortic and mitral valve anatomy and function is recommended in ACHD patients with SupraAS. (Level of Evidence: C)
5. Adults with a history or presence of SupraAS should be screened periodically for myocardial ischemia. (Level of Evidence: C)
1. Exercise testing, dobutamine stress testing, positron emission tomography, or stress sestamibi with adenosine studies can be useful to evaluate the adequacy of myocardial perfusion. (Level of Evidence: C)
6.10.1. Clinical Examination
Preferential flow (Coanda effect) up the rightward portion of the ascending aorta into the right brachiocephalic artery may produce discordant amplitude of arterial pulsations in the carotids and upper extremities. There may also be a differential blood pressure between the right and left arm. A systolic thrill in the suprasternal notch is common. There may be a dynamic LV apical impulse. The second heart sound may be narrowly or paradoxically split. A fourth heart sound may be present over the LV apical thrust. An ejection click is absent. There is a crescendo-decrescendo murmur at the cardiac base, with radiation to the right side of the neck. Careful auscultation over the back and flank may reveal murmurs of peripheral pulmonary artery stenosis or renal artery stenosis. Hypertension and an abdominal bruit may signify renal artery stenosis.
The ECG may reveal LV hypertrophy and secondary ST-T–wave abnormalities versus ischemic changes, depending on the severity of LVOT obstruction and the degree of coronary involvement. ST-T–wave changes may not regress after surgery, even if the gradient has been relieved; therefore, it is important to determine whether these postoperative abnormalities are recent versus chronic.
6.10.3. Chest X-Ray
The chest x-ray is often normal but may reveal LV hypertrophy or asymmetry of the aortic knob.
TTE and TEE demonstrate the diameter and anatomy of the aortic sinus, sinotubular ridge, and proximal ascending aorta, the origins of the coronary arteries, the systolic gradient across the SupraAS obstruction, and the degree of LV hypertrophy. MRI/CT is required to more precisely define the anatomy of the aorta and branches, as well as the pulmonary arteries. As with any long-segment obstruction, assessment of the gradient can be challenging and may require cardiac catheterization for complete assessment of hemodynamic severity of the stenosis. Patients with Williams syndrome should have imaging of the entire aorta, including the renal arteries, because of the association with arterial stenosis at any level.
6.10.5. Stress Testing
Stress testing may be helpful to assess coronary involvement and LV compensation.
6.10.6. Myocardial Perfusion Imaging
Noninvasive screening for coronary insufficiency may be helpful if there are symptoms or ECG findings of ischemia or if there is significant coronary involvement on imaging studies. Patients with limited cognitive function may be unable to perform maximal stress testing but pharmacological stress (adenosine or dobutamine) nuclear imaging with positron emission tomography, single photon emission computed tomography, or MRI may be performed.
6.10.7. Cardiac Catheterization
Diagnostic catheterization may help to delineate anatomy and accurately measure gradients. Selective coronary angiography should be approached with caution after thorough noninvasive and angiographic examination of the aortic root, because coronary ostial stenosis is a frequent occurrence in this population. Intravascular ultrasonography may provide definition of coronary artery anatomy and define the nature and extent of the diseased vessel before consideration of repair.
6.11. Management Strategies for Supravalvular Left Ventricular Outflow Tract
6.11.1. Recommendations for Interventional and Surgical Therapy
1. Operative intervention should be performed for patients with supravalvular LVOT obstruction (discrete or diffuse) with symptoms (ie, angina, dyspnea, or syncope) and/or mean gradient greater than 50 mm Hg or peak instantaneous gradient by Doppler echocardiography greater than 70 mm Hg. (Level of Evidence: B)
2. Surgical repair is recommended for adults with lesser degrees of supravalvular LVOT obstruction and the following indications:
a. Symptoms (ie, angina, dyspnea, or syncope). (Level of Evidence: B)
b. LV hypertrophy. (Level of Evidence: C)
c. Desire for greater degrees of exercise or a planned pregnancy. (Level of Evidence: C)
d. LV systolic dysfunction. (Level of Evidence: C)
3. Interventions for coronary artery obstruction in patients with SupraAS should be performed in ACHD centers with demonstrated expertise in the interventional management of such patients. (Level of Evidence: C)
Surgical relief of SupraAS is accomplished with the use of complex patching of the aorta, with reconstruction of the coronary ostia or bypass grafting, depending on the anatomy of the lesion. Surgical results with reconstruction of the coronary ostium or bypass grafting, depending on anatomy of the lesions noted, have been described without long-term follow-up (365). Branch pulmonary artery stenosis may be addressed during the same surgical procedure. There are no long-term follow-up data on adults after surgery for SupraAS. Catheter-based techniques have not been described for this lesion.
6.11.2. Recommendations for Key Issues to Evaluate and Follow-Up
1. Both operated and unoperated patients with SupraAS should be followed up annually at a regional ACHD center. (Level of Evidence: C)
2. Long-term psychosocial assessment and oversight, including the need for legal guardianship, are recommended for patients with Williams syndrome. (Level of Evidence: C)
Repair of SupraAS results in low early and late mortality and low incidence of recurrent obstruction. The durability of patch material requires long-term observation for assessment of aneurysm formation. Both operated and unoperated patients with SupraAS require lifelong annual follow-up to evaluate the degree of obstruction and LV compensation, the development of coronary insufficiency or systemic hypertension, and the development of mitral regurgitation.
Patients with Williams syndrome require long-term psychosocial follow-up to assess competency for self-care and recommend appropriate measures. This is particularly important because these patients have verbal and social skills that result in an overestimation of their executive functioning.
6.11.3. Special Issues
In SupraAS, abnormal systolic forces on the proximal coronary arteries and ostia may accelerate coronary artery disease, and impaired diastolic coronary filling due to ostial obstruction may cause or augment myocardial ischemia. Care must be taken to avoid circumstances that decrease diastolic pressure so that critical coronary perfusion is maintained.
6.11.4. Exercise and Athletics
Refer to Section 6.7.2, Activity/Exercise.
6.11.5. Recommendations for Reproduction
1. SupraAS, whether associated with Williams syndrome or nonsyndromic, has a strong likelihood of being an inherited disorder. Undetected family members may be at risk for hypertension, coronary disease, or stroke; therefore, all available relatives should be screened. (Level of Evidence: C)
2. Patients with SupraAS and significant obstruction, coronary involvement, or aortic disease should be counseled against pregnancy. (Level of Evidence: C)
6.12. Aortic Coarctation
Discrete coarctation of the aorta consists of short-segment narrowing in the region of the ligamentum arteriosum adjacent to the origin of the left subclavian artery. In some cases, there is also narrowing of the aortic arch or isthmus. Extensive collateral vessels may arise proximal to the obstruction. The presence of abundant collaterals may reduce the gradient across the coarctation and mask the severity of the obstruction. An associated intrinsic abnormality in the aortic wall predisposes to dissection or rupture in the ascending aorta or the area of the coarctation. The adult who had surgical repair of coarctation of the aorta as an infant is more likely to have associated cardiac lesions with BAV, SubAS, VSD, and varying degrees of arch hypoplasia. Residual hemodynamic problems from any of these defects may complicate the clinical course and may require more detailed evaluation and follow-up.
6.12.2. Associated Lesions
Associated lesions include BAV, SubAS, mitral valve abnormalities such as parachute mitral stenosis, VSD, and circle of Willis cerebral artery aneurysm.
6.12.3. Recommendations for Clinical Evaluation and Follow-Up
1. Every patient with systemic arterial hypertension should have the brachial and femoral pulses palpated simultaneously to assess timing and amplitude evaluation to search for the “brachial-femoral delay” of significant aortic coarctation. Supine bilateral arm (brachial artery) blood pressures and prone right or left supine leg (popliteal artery) blood pressures should be measured to search for differential pressure. (Level of Evidence: C)
2. Initial imaging and hemodynamic evaluation by TTE, including suprasternal notch acoustic windows, is useful in suspected aortic coarctation. (Level of Evidence: B)
3. Every patient with coarctation (repaired or not) should have at least 1 cardiovascular MRI or CT scan for complete evaluation of the thoracic aorta and intracranial vessels. (Level of Evidence: B)
Aortic coarctation may be recognized in the adult, usually because of systemic arterial hypertension and discrepant upper- and lower-extremity pulses. Patients may complain of exertional headaches, leg fatigue, or claudication. Occasionally, the patient may come to medical attention because of a murmur due to BAV or VSD.
Unoperated survival averages 35 years of age, with 75% mortality by 46 years of age. Systemic hypertension, accelerated coronary heart disease, stroke, aortic dissection, and congestive heart failure are common complications in patients who have not had surgery or who are operated on in later childhood or adult life. An associated BAV with varying degrees of AS or AR may be present. Death may be related to congestive heart failure, aortic rupture/dissection, endocarditis/endarteritis, intracerebral hemorrhage, or myocardial infarction.
6.13. Clinical Features and Evaluation of Unrepaired Patients
Hypertension is present in the right arm, relative to the lower extremities, unless an anomalous origin of the right subclavian artery is present. The left subclavian artery may be close to the aortic narrowing and thus may or may not be hypertensive. The carotid pulsations may be hyperdynamic. There is a pulse delay between the right arm and the femoral or popliteal arteries. A murmur or bruit may be heard in the left interscapular position, either due to the coarctation or to collaterals. If collateral vessels are present, continuous murmurs may be present over the parasternal areas (mammary arteries) and around the left scapula; occasionally, periscapular collaterals can be palpated. Auscultation should be directed toward detecting a parasternal and apical systolic ejection sound suggestive of an associated BAV with or without a systolic crescendo-decrescendo murmur of LVOT obstruction or an early diastolic decrescendo murmur of AR.
The ECG may demonstrate LV hypertrophy and secondary ST-T–wave abnormalities but occasionally will show RV conduction delay.
6.13.2. Chest X-Ray
An anterior-posterior projection of the chest x-ray may show a prominent curvilinear shadow along the mid-right sternal border that represents a dilated ascending aorta. An indentation at the coarctation site may produce a “3 sign” adjacent to the area beneath the transverse arch and above the main pulmonary artery silhouette. Notching on the underside of the ribs (usually 3 to 9) from collateral vessels may be apparent.
6.13.3. Echocardiography and Doppler
The coarctation may be demonstrated on a suprasternal notch view of the aortic arch and proximal descending aorta, which, when combined with color flow imaging and continuous-wave spectral Doppler interrogation, may demonstrate turbulence in the proximal descending aorta and show the characteristic flow profile of forward diastolic flow. An abnormal Doppler flow pattern may also be noted in the abdominal aorta, ie, decreased pulsatility and absence of early diastolic flow reversal. Abnormal flow in collateral vessels can be detected by color flow and pulse Doppler. It is also important to measure the dimensions of the aortic annulus, aortic sinuses, sinotubular ridge, and ascending aorta. The anatomy of the aortic valve should be determined, as well as LV size, mass, and function. Careful investigation should rule out associated lesions such as VSD, SubAS, and mitral valve deformity.
6.13.4. Stress Testing
In addition to the usual evaluation of exercise capacity and symptoms, rhythm, and ECG response, stress testing goals include assessment of the systemic arterial blood pressure response at rest and with exercise, which is a surrogate evaluation of the coarctation gradient. Stress-echocardiography–Doppler is valuable and is targeted at obtaining the rest and exercise suprasternal notch continuous-wave Doppler coarctation gradient, including the diastolic profile. Arm-leg blood pressure and echocardiography-Doppler gradient assessment during exercise may be problematic and better assessed with supine ergometer stress testing or dobutamine stress testing.
6.13.5. Magnetic Resonance Imaging/Magnetic Resonance Angiography or Computed Tomography With 3-Dimensional Reconstruction
MRI or CT angiography with 3-dimensional reconstruction identifies the precise location and anatomy of the coarctation and entire aorta, as well as collateral vessels (366). Magnetic resonance angiography to search for aneurysms of the intracranial arteries is appropriate. Magnetic resonance angiography may also be useful to quantify collateral flow.
6.13.6. Catheterization Hemodynamics/Angiography
Diagnostic cardiac catheterization is mainly justified when associated coronary artery disease is suspected and surgery is planned; however, MRI/magnetic resonance angiography or CT remains the preferred means of imaging the area of coarctation. Cardiac catheterization is also indicated if catheter-based intervention (angioplasty or stent) is to be performed, and generally, this should be performed only in centers with interventional capability.
6.13.7. Problems and Pitfalls
In the presence of sizable collaterals, femoral pulses may be less diminished, and catheter-based and Doppler systolic gradients may not capture the degree of obstruction of aortic coarctation and hence may be misleading. Repair of coarctation late in childhood or in adult life often does not prevent persistence or late recurrence of systemic hypertension. Hypertension can also reappear several years after coarctation repair.
6.14. Management Strategies for Coarctation of the Aorta
6.14.1. Medical Therapy
Hypertension should be controlled by beta blockers, ACE inhibitors, or angiotensin-receptor blockers as first-line medications. The choice of beta blockers or vasodilators may be influenced in part by the aortic root size, the presence of AR, or both.
6.14.2. Recommendations for Interventional and Surgical Treatment of Coarctation of the Aorta in Adults
1. Intervention for coarctation is recommended in the following circumstances:
a. Peak-to-peak coarctation gradient greater than or equal to 20 mm Hg. (Level of Evidence: C)
b. Peak-to-peak coarctation gradient less than 20 mm Hg in the presence of anatomic imaging evidence of significant coarctation with radiological evidence of significant collateral flow. (Level of Evidence: C)
2. Choice of percutaneous catheter intervention versus surgical repair of native discrete coarctation should be determined by consultation with a team of ACHD cardiologists, interventionalists, and surgeons at an ACHD center. (Level of Evidence: C)
3. Percutaneous catheter intervention is indicated for recurrent, discrete coarctation and a peak-to-peak gradient of at least 20 mm Hg. (Level of Evidence: B)
4. Surgeons with training and expertise in CHD should perform operations for previously repaired coarctation and the following indications:)
a. Long recoarctation segment. (Level of Evidence: B)
b. Concomitant hypoplasia of the aortic arch. (Level of Evidence: B)
1. Stent placement for long-segment coarctation may be considered, but the usefulness is not well established, and the long-term efficacy and safety are unknown. (Level of Evidence: C)
The appropriate type of treatment for native coarctation of the aorta in adults remains somewhat controversial. In particular, for women who are or will be of childbearing age after repair, there is a concern about the tissue integrity of the paracoarctation region, particularly during pregnancy. As such, one may select direct surgical repair with excision of the paracoarctation tissue for those individuals. For recurrent aortic coarctation (coarctation after surgical repair), the prevailing opinion now is that catheter-based intervention (balloon or stent) is generally safe and the preferred alternative to surgery in the absence of confounding features (eg, aneurysm or pseudoaneurysm formation, or significant coarctation that affects the adjoining arch arterial branches).
McCrindle et al reported the recurrence rate after balloon angioplasty of primary coarctation in adults at approximately 7%, with a further 7% of patients having a suboptimal primary outcome (367). For localized discrete narrowing, balloon angioplasty is an acceptable alternative to surgical repair as a primary intervention but is still considered less suitable for long-segment or tortuous forms of coarctation.
In the majority of circumstances, discrete recoarctation is managed with balloon dilation with or without stent placement. In many ACHD centers, surgery is reserved for patients who are unsuitable for percutaneous treatment or who have undergone unsuccessful percutaneous treatment.
Reoperation is performed via midline sternotomy or posterolateral thoracotomy, depending on the precise form of repair required for a given individual and whether associated lesions (BAV disease, dilated aortic root) need to be addressed simultaneously. The use of partial or full cardiopulmonary bypass may be required to prevent paralytic complications. Intervention, whether via a catheter approach or surgery, should be done in centers with experience in the medical and surgical care of ACHD patients.
Early mortality is usually less than 1% for primary operation. Early mortality is higher for reoperation (1% to 3%) and can be as high as 5% to 10% if there are significant comorbidities or significant LV dysfunction. Rebound hypertension can occur early after repair and may be prevented or blunted by preoperative administration of a beta blocker. Morbidity in adults with reoperation for coarctation can be considerable and may include significant early postoperative bleeding, pleural effusion, lung contusion, recurrent laryngeal nerve palsy, or phrenic nerve injury (with hemidiaphragmatic paresis or paralysis). Other postoperative complications include recoarctation and hypertension. Aneurysm formation at the repair site can occur after patch aortoplasty (particularly with the use of a Dacron patch) or resection of the coarctation shelf. False aneurysms may also occur at the repair site. Late dissection proximal or distal to the repair site can occur. Paraplegia secondary to spinal cord ischemia is rare but is more common with poor collateral circulation. Arm claudication or subclavian steal syndrome is rare but in particular may occur after use of the subclavian flap technique.
6.14.3. Recommendations for Key Issues to Evaluate and Follow-Up
1. Lifelong cardiology follow-up is recommended for all patients with aortic coarctation (repaired or not), including an evaluation by or consultation with a cardiologist with expertise in ACHD. (Level of Evidence: C)
2. Patients who have had surgical repair of coarctation at the aorta or percutaneous intervention for coarctation of the aorta should have at least yearly follow-up. (Level of Evidence: C)
3. Even if the coarctation repair appears to be satisfactory, late postoperative thoracic aortic imaging should be performed to assess for aortic dilatation or aneurysm formation. (Level of Evidence: B)
4. Patients should be observed closely for the appearance or reappearance of resting or exercise-induced systemic arterial hypertension, which should be treated aggressively after recoarctation is excluded. (Level of Evidence: B)
5. Evaluation of the coarctation repair site by MRI/CT should be performed at intervals of 5 years or less, depending on the specific anatomic findings before and after repair. (Level of Evidence: C)
1. Routine exercise testing may be performed at intervals determined by consultation with the regional ACHD center. (Level of Evidence: C)
All patients with either interventional catheterization or surgical repair of coarctation of the aorta should have close follow-up and aggressive management of blood pressure and other risk factors for cardiovascular disease. This should include at least yearly cardiology evaluations. Consultation with a cardiologist with special expertise in ACHD should be obtained on initial contact to determine risk factors specific for the patient's anatomy and the presence of associated lesions. Evaluation of the repair site by MRI/CT should be repeated at intervals of 5 years or less, depending on the specific anatomic findings before and after repair. Consideration should be given to cumulative lifetime radiation exposure with multiple CT examinations.
6.14.4. Exercise and Athletics
Exercise and athletics have been addressed recently by the 36th Bethesda Conference (49). Significant residual or unrepaired coarctation, associated BAV with AS, or a dilated aortic root warrants prohibition of contact sports, isometric or heavy weight lifting, and sudden stop-start sports. It would be prudent to have a cardiology consultation, stress testing, and an echocardiogram before permitting low- to moderate-level dynamic sports or light weight lifting.
Pregnancy in coarctation of the aorta continues to be a source of concern, but major cardiovascular complications are infrequent (368). An assessment of the hemodynamic status, severity of coarctation, and associated lesions, particularly BAV, AS, or a significantly dilated root, should be undertaken before pregnancy for proper planning and advice. The potential for aortic dissection remains, although it is quite small unless the aorta is dilated significantly.
6.14.6. Endocarditis Prophylaxis
Patients with uncomplicated native coarctation or uncomplicated, recurrent coarctation that is successfully repaired do not require endocarditis prophylaxis unless there is a prior history of endocarditis or a conduit has been inserted or if surgical repair or stenting has been performed less than 6 months previously (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).
7. Right Ventricular Outflow Tract Obstruction
Obstruction to the RVOT in the adult patient can be either congenital or acquired. Table 13 summarizes the various forms.
Congenital obstruction can be at the pulmonary valve, below the pulmonary valve, or above the pulmonary valve. Below the pulmonary valve, obstruction can be either at the infundibular or the subinfundibular level. Infundibular stenosis is a crucial component of tetralogy of Fallot (369). Other congenital forms of infundibular stenosis include reactive myocardial hypertrophy that is secondary to pulmonary valvular stenosis or, much less commonly, stenosis of the ostium of the infundibulum itself. Case reports of other causes include a pouch of accessory tricuspid valve tissue or an accessory tricuspid valve leaflet (370), fibrous tags from the valve openings of the inferior vena cava or coronary sinus that obstruct the RVOT (371), and aneurysms of either the aortic sinus of Valsalva (372,373) or the membranous interventricular septum (374).
Subinfundibular stenosis or double-chambered right ventricle is a rare form of outflow obstruction that results in the RV being divided into a high-pressure inlet portion and a low-pressure outlet portion by a thick muscle bundle, the hypertrophied septoparietal trabeculation, an anomalous apical shelf, or an abnormal moderator band (375,376). The degree of obstruction can vary widely, and an associated VSD is common.
The sequelae from surgical intervention may also result in stenosis, at times requiring reintervention. Postoperatively, valvular or conduit stenosis and regurgitation of implanted bioprosthetic pulmonary valves placed during childhood are expected outcomes for many patients when they reach adulthood. Pulmonary valve and trunk stenosis of the pulmonary homograft in patients undergoing the Ross procedure has been a particularly difficult problem, seen in up to 20% of patients in some series (377). Postoperative conduit stenosis and regurgitation are also major issues for patients with tetralogy of Fallot.
7.2. Associated Lesions
Pulmonary valvular, subvalvular, or supravalvular stenosis may be an associated lesion in many patients with other forms of complex CHD. In addition, a markedly dilated pulmonary main trunk consistent with a low-pressure pulmonary artery aneurysm may be present and is occasionally seen with PS. These large main pulmonary artery aneurysms may achieve considerable size and may appear as a mediastinal mass on chest x-ray. They are usually asymptomatic, but in rare situations, they compress contiguous areas such as the left main coronary artery and then cause chest pain. Rupture is extremely rare in these low-pressure, highly elastic vessels, and so, in and of themselves, they do not require intervention (378). This is in marked contrast to hypertensive pulmonary aneurysms, which may rupture.
7.3. Valvular Pulmonary Stenosis
Valvular PS is usually an isolated lesion, occurs in approximately 7% to 12% of all CHD, and accounts for 80% to 90% of all lesions that cause RVOT obstruction (379). Its inheritance rate is low, ranging from 1.7% to 3.6% (380,381). Approximately 20% of patients with valvular PS have a dysplastic valve (382,383), and if part of Noonan syndrome, these patients have an autosomal dominant trait with variable penetrance that has been mapped to chromosome 12 (384,385).
There are 3 morphological types of clinical significance.
1. The typical dome-shaped pulmonary valve is characterized by a narrow central opening but a preserved, mobile valve mechanism. Three rudimentary raphes are usually present, but clear-cut commissures are not identifiable. The pulmonary trunk is dilated, mostly owing to an inherent medial abnormality. The jet from the stenotic valve tends to favor flow to the left pulmonary arterial branch. Calcification of the valve is occasionally seen in older adult patients.
2. The dysplastic pulmonary valve is less common. The leaflets are poorly mobile, and there is marked myxomatous thickening with no commissural fusion. The pulmonary annulus and the outflow tract may also be narrowed. The lesion is a frequent component of the Noonan syndrome.
3. The unicuspid or bicuspid pulmonary valve is generally a feature of tetralogy of Fallot. It may or may not create significant obstruction itself.
PS is considered mild when the peak gradient across the valve is less than 30 mm Hg, moderate when the gradient is 30 to 50 mm Hg, and severe when the gradient is greater than 50 mm Hg.
7.4. Clinical Course
7.4.1. Unrepaired Patients
Valvular PS usually presents with an asymptomatic systolic murmur, but occasionally, a patient will present with exercise intolerance. Stenosis is rarely progressive when the initial gradient is mild, but moderate PS can progress owing to progressive valve stenosis or reactive hypertrophy of the infundibulum.
The outcome of medically managed patients with PS was discussed in the Second Natural History Study (104). Patients with peak-to-peak catheterization-derived gradients greater than 80 mm Hg underwent pulmonary valvotomy. Patients with gradients greater than 50 mm Hg clearly did worse than those with gradients less than 50 mm Hg (104).
7.4.2. Noonan Syndrome Patients With Prior Repair
For the most part, the clinical issues regarding when to intervene in the postoperative patient are similar to those for patients before surgery. The main difference is in the presence of valvular regurgitation. In low-pressure pulmonary regurgitation (mean pulmonary artery pressure less than 20 mm Hg), the diastolic gradient between the RV and pulmonary artery may be quite small, and significant pulmonary regurgitation may be difficult to detect. Restenosis after percutaneous valvuloplasty is more common if a residual gradient greater than 30 mm Hg remains immediately after the procedure. A dilated pulmonary artery may not decrease in size after pulmonary valve intervention.
7.5. Recommendations for Evaluation of the Unoperated Patient
1. Two-dimensional echocardiography-Doppler, chest x-ray, and ECG are recommended for the initial evaluation of patients with valvular PS. (Level of Evidence: C)
2. A follow-up physical examination, echocardiography-Doppler, and ECG are recommended at 5-year intervals in the asymptomatic patient with a peak instantaneous valvular gradient by Doppler less than 30 mm Hg. (Level of Evidence: C)
3. A follow-up echocardiography-Doppler is recommended every 2 to 5 years in the asymptomatic patient with a peak instantaneous valvular gradient by Doppler greater than 30 mm Hg. (Level of Evidence: C)
1. Cardiac catheterization is unnecessary for diagnosis of valvular PS and should be used only when percutaneous catheter intervention is contemplated. (Level of Evidence: C)
7.5.1. Clinical Examination
Most adult patients with PS are normal in appearance. In the Noonan syndrome, there is characteristically short stature, webbed neck, hypertelorism, lymphedema, low-set ears and hairlines, hyperelastic skin, chest deformities (eg, flat, pectus excavatum or pectus carinatum), and micrognathia (383). Approximately one third of Noonan patients are mentally disabled, and cryptorchidism is common.
The cardiac examination of a patient with PS is dependent on the severity of stenosis, the pathology of the valve, and any associated cardiac lesions. The physical examination in mild PS is characterized by a normal jugular venous pulse, no RV lift, and a pulmonary ejection sound that tends to decrease with inspiration. It is the only right-sided auscultatory event that decreases with inspiration (owing to premature opening of the pulmonary valve by the atrial kick into the stiff RV). A pulmonary ejection murmur that increases with inspiration is usually heard ending in mid systole. In severe PS, there is usually an elevated jugular venous pressure with a prominent “A” wave. An RV lift is common, and there is a much louder and longer pulmonary ejection murmur with loss of the ejection sound. Wide splitting of S2 may be present, and P2 may be reduced or absent. A right-sided S4 may also be heard. Evidence for right-sided heart failure is uncommon until late in the disease process.
The ECG is usually normal when the RV systolic pressure is less than 60 mm Hg, but more severe obstruction leads to right atrial enlargement, right-axis deviation, and RV hypertrophy (386).
7.5.3. Chest X-Ray
The heart size on chest x-ray is normal unless there is an associated cardiac lesion. Vascular fullness in the left lung base greater than the right base (Chen's sign) is due to the preferential pulmonary flow to the left lung in patients with PS (387). Dilatation of the main pulmonary artery is common in doming PS but not in dysplastic PS. Calcification of the valve may rarely be seen in older patients. The right atrium may be enlarged.
TTE is generally definitive, but in some patients, TEE may better define the anatomy of the RVOT. A Doppler gradient is readily determined and is used to define when to intervene. Pulmonary valve mobility can also be assessed, along with the presence of other cardiac lesions, and RV function can be semiquantified. Saline microcavitations can help define any right-to-left shunt due to a PFO. When the PS is severe, systolic interventricular septal flattening may be present. In patients with a dysplastic pulmonary valve, the valve can be seen to be thickened and immobile, with the absence of poststenotic dilation of the main pulmonary artery. Evidence of pulmonary regurgitation should be sought by Doppler examination.
7.5.5. Magnetic Resonance Imaging/Computed Tomography
In uncomplicated valvular PS, the use of MRI or CT is simply confirmatory. These studies do provide excellent imaging of the main, branch, and peripheral pulmonary arteries and are useful when these associated lesions are of concern or to assess the degree of pulmonary regurgitation or TR.
7.5.6. Cardiac Catheterization
Cardiac catheterization is rarely necessary for diagnosis. Gradients above, at, and below the pulmonic valve should be obtained. A peak RV systolic pressure of less than 35 mm Hg and a systolic pulmonary valve gradient of less than 10 mm Hg are considered the upper limits of normal. RV angiography helps define contractile function, the presence of infundibular obstruction, and mobility of the pulmonary valve. Angiography of the pulmonary artery can assess the degree of pulmonary regurgitation and any stenotic lesions in the main, branch, or peripheral pulmonary arteries.
There is little progression in PS severity when the gradient is less than 30 mm Hg; such patients can be followed up at least every 5 years with a clinical examination and Doppler echocardiogram. Those with more significant stenosis should be followed up on a yearly basis. Most patients with PS who reach adulthood are asymptomatic and require no specific therapy. If a dynamic outflow tract obstruction exists, therapy with drugs that slow the heart rate and improve diastolic filling time (ie, beta blockers) (388) and those that might potentially reduce the systolic gradient and improve lusitropy (ie, calcium channel blockers and disopyramide) may also be used clinically, in a manner similar to that in patients with hypertrophic cardiomyopathy and other diseases of LV diastolic dysfunction. Elevated right-sided heart pressures, edema, and ascites can be treated with thiazides, loop diuretics, and aldosterone antagonists as appropriate.
7.5.7. Relationship Between Peak Instantaneous Doppler Echocardiographic Pressure Gradients and Peak-to-Peak Cardiac Catheterization Gradients
The 2006 ACC/AHA valvular heart disease guidelines and much of the older literature used the catheter-derived peak-to-peak gradient across the pulmonary valve to determine when to intervene in valvular PS (112). Patients with valvular PS do not require cardiac catheterization for diagnosis, however, and the relationship between the peak-to-peak invasive hemodynamic gradient and the Doppler peak instantaneous gradient becomes relevant in deciding appropriateness for invasive evaluation and intervention. There are recent data that suggest the peak-to-peak gradient by cardiac catheterization correlates best with the mean Doppler (and not peak instantaneous Doppler) gradient in this situation (389) and that the peak instantaneous gradient systematically overestimates the peak-to-peak cardiac catheterization gradient by slightly more than 20 mm Hg. Correlation of the echocardiography-Doppler gradient with other clinical findings is important.
7.6. Problems and Pitfalls
In the adult, the symptoms related to PS may be confused with a variety of other conditions that need to be considered. Some of these are noted below. A pulmonary velocity of up to 2.5 m per s may be detected by echocardiography-Doppler in patients with an ASD or pulmonary regurgitation. This relates only to increased flow across the pulmonary valve and does not imply coexistent PS.
Dyspnea occurs in patients with severe PS. Whenever symptoms do not match the severity of the anatomy (ie, symptoms with a PS gradient less than 50 mm Hg or no symptoms and a severe PS gradient), exercise studies are often helpful in assessment of functional capacity. A determination of maximal oxygen consumption along with exercise duration is also useful.
7.6.2. Chest Pain
In the older patient or one with multiple risk factors for coronary artery disease, if angina-type symptoms are present, a stress imaging study should be done to help screen for functional coronary artery disease. Markedly enlarged pulmonary artery aneurysms may rarely cause chest pain by compression of the left main coronary artery.
7.6.3. Enlarging Right Ventricle
Progressive RV dilation in patients with PS suggests an associated lesion such as ASD. In the postoperative patient, this may imply restenosis or pulmonary regurgitation. The severity of low-pressure pulmonary regurgitation may be difficult to diagnose clinically or by echocardiography, because the RV end-diastolic pressure may be only a few millimeters of mercury below the pulmonary arterial end-diastolic pressure. This results in a minor diastolic gradient that is difficult to detect by auscultation and color Doppler because the flow is laminar. Occasionally, imaging with MRI or pulmonary angiography may be required.
7.6.4. Pulmonary Arterial Hypertension
Patients with isolated valvular PS are not expected to have PAH. If evidence of PAH is present, then other causes must be considered, such as associated peripheral pulmonary artery stenosis. Patients who had a systemic–to–pulmonary artery shunt as a child may have branch pulmonary artery stenosis at the site of the anastomosis. In some postoperative patients, repair of the PS may have been only part of a larger surgical procedure that included a late VSD closure or patent ductus repair, and pulmonary vascular disease may now complicate the clinical picture.
Cyanosis is usually not part of RVOT lesions, unless there is an associated ASD or a substantial increase in right atrial pressure and right-to-left shunting through a PFO. Otherwise, one should seek an alternative source of the cyanosis.
7.6.6. Systemic Venous Congestion
The presence of systemic venous congestion suggests significant RV dysfunction and is an uncommon finding in isolated PS. Exceptions occasionally seen in adults are those patients with cor pulmonale due to intrinsic lung disease or to left-sided heart disease, those with constrictive pericarditis or a restrictive cardiomyopathy, and those with severe TR due to other causes (eg, endocarditis, percutaneous pacemaker, or Ebstein's anomaly). These diagnoses must be excluded before the right-sided heart failure is attributed to PS.
7.7. Management Strategies
There is no specific medical therapy for valvular PS. If right-sided heart failure occurs, it is treated primarily with diuretics. There are few data to support the efficacy of digoxin in this circumstance. Patients with atrial arrhythmias often require either antiarrhythmic therapy, ablation, or both. Sudden death is very rare (390). The treatment of significant PS is either by percutaneous balloon valvuloplasty or by surgical intervention.
7.7.1. Recommendations for Intervention in Patients With Valvular Pulmonary Stenosis
1. Balloon valvotomy is recommended for asymptomatic patients with a domed pulmonary valve and a peak instantaneous Doppler gradient greater than 60 mm Hg or a mean Doppler gradient greater than 40 mm Hg (in association with less than moderate pulmonic valve regurgitation). (Level of Evidence: B)
2. Balloon valvotomy is recommended for symptomatic patients with a domed pulmonary valve and a peak instantaneous Doppler gradient greater than 50 mm Hg or a mean Doppler gradient greater than 30 mm Hg (in association with less than moderate pulmonic regurgitation). (Level of Evidence: C)
3. Surgical therapy is recommended for patients with severe PS and an associated hypoplastic pulmonary annulus, severe pulmonary regurgitation, subvalvular PS, or supravalvular PS. Surgery is also preferred for most dysplastic pulmonary valves and when there is associated severe TR or the need for a surgical Maze procedure. (Level of Evidence: C)
4. Surgeons with training and expertise in CHD should perform operations for the RVOT and pulmonary valve. (Level of Evidence: B)
1. Balloon valvotomy may be reasonable in asymptomatic patients with a dysplastic pulmonary valve and a peak instantaneous gradient by Doppler greater than 60 mm Hg or a mean Doppler gradient greater than 40 mm Hg. (Level of Evidence: C)
2. Balloon valvotomy may be reasonable in selected symptomatic patients with a dysplastic pulmonary valve and peak instantaneous gradient by Doppler greater than 50 mm Hg or a mean Doppler gradient greater than 30 mm Hg. (Level of Evidence: C)
1. Balloon valvotomy is not recommended for asymptomatic patients with a peak instantaneous gradient by Doppler less than 50 mm Hg in the presence of normal cardiac output. (Level of Evidence: C)
2. Balloon valvotomy is not recommended for symptomatic patients with PS and severe pulmonary regurgitation. (Level of Evidence: C)
3. Balloon valvotomy is not recommended for symptomatic patients with a peak instantaneous gradient by Doppler less than 30 mm Hg. (Level of Evidence: C)
7.7.2. Percutaneous Balloon Pulmonary Valvotomy
Since the initial successful report of percutaneous balloon valvotomy for pulmonary valve stenosis in 1982 (391), the procedure has evolved to become the treatment of choice for patients with classic domed valvular PS. Balloon valvotomy produces relief of the gradient by commissural splitting. As might be expected from the morphology, results in patients with a dysplastic pulmonary valve are less impressive. In the Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) registry, in 784 cases, the mean transvalvular gradient declined from 71 to 28 mm Hg in patients with typical PS and from 79 to 49 mm Hg in patients with a dysplastic valve (392).
The procedure is usually performed from the right femoral vein. Because of the elasticity of the pulmonary annulus, it has been found that oversizing the balloons up to 1.4 times the measured pulmonary annulus is more effective in achieving a successful result (usually defined by a final valvular gradient of less than 20 mm Hg). To accomplish this oversizing in adults, a double-balloon procedure is frequently used. In general, acute complications from the procedure have been minimal. During the acute performance of the valvotomy, vagal symptoms predominate, along with catheter-induced ventricular ectopy and occasionally right bundle-branch block. Other complications include pulmonary valve regurgitation, pulmonary edema (presumably from increasing pulmonary blood flow to previously underperfused lungs), cardiac perforation and tamponade, high-grade AV nodal block, and transient RVOT obstruction. The latter is sometimes referred to as a “suicidal right ventricle” and is due to abrupt infundibular obstruction once the pulmonary valve obstruction has been relieved (393). This may be alleviated by volume expansion and beta blockade. This postprocedural infundibular obstruction tends to regress over time.
7.7.3. Surgical Pulmonary Valvotomy or Valve Replacement
In 1948, the first pulmonary valve commissurotomies were reported by Sellors (394). Varco introduced the technique of “blind” pulmonary valvotomy in 1951 (395), although better results were found with direct visualization and open techniques quickly became the norm. In patients with a dysplastic valve, partial or total valvectomy was required, and often, a transannular patch was needed owing to annular or pulmonary trunk hypoplasia. Residual pulmonary valve regurgitation is commonplace with all these procedures (396), and late pulmonary valve replacement is often necessary decades later.
In patients with PS and significant valvular regurgitation, valve replacement may be required. Mechanical valve replacement (397) is rarely used because of concerns regarding thrombosis and the potential need for measurement of pulmonary pressures; mechanical PVR can be considered in selected patients who have had multiple previous operations and are undergoing warfarin therapy because of another mechanical valve prosthesis. Owing to low pulmonary artery pressure and slow flow despite anticoagulation, there is a high risk of valve thrombosis with mechanical prosthetic valves in the pulmonary position. Bioprosthetic valves (398) can be effectively implanted with good durability in patients of all ages, although valvular degeneration eventually ensues in all. The bovine jugular vein valved xenograft has also been used with good early but mixed late results (399). Although pulmonary homograft replacement (398) is a popular means of surgical reconstruction in children, it has limited durability in the adult patient, especially in the setting of elevated pulmonary artery pressures. Stenosis of the pulmonary homograft has been a particular issue in patients undergoing the Ross procedure (400).
In patients with a markedly dilated main pulmonary artery associated with PS, there are no guidelines to suggest a particular size that requires operative intervention. Because these are low-pressure aneurysms that rarely, if ever, rupture, the decision to intervene surgically is usually a function of whether they are symptomatic, are compressing contiguous structures, or are associated with pulmonary regurgitation and subsequent right ventricle enlargement (378). In these patients, reduction pulmonary arterioplasty or main pulmonary artery replacement with a tube graft or valved tube graft can be accomplished.
Early mortality for isolated pulmonary valve operation is approximately 1% in children. There are no comparable adult data. Freedom from reoperation for bioprosthetic valve deterioration is approximately 90% at 10 years. Residual obstruction may progress. Pulmonary regurgitation may occur; progression of pulmonary regurgitation may eventually necessitate pulmonary valve replacement. Late survival is similar to that of an age-matched population when valvular RVOT obstruction occurs as an isolated lesion.
7.8. Recommendation for Clinical Evaluation and Follow-Up After Intervention
1. Periodic clinical follow-up is recommended for all patients after surgical or balloon pulmonary valvotomy, with specific attention given to the degree of pulmonary regurgitation; RV pressure, size, and function; and TR. The frequency of follow-up should be determined by the severity of hemodynamic abnormalities but should be at least every 5 years. (Level of Evidence: C)
The murmur of pulmonary regurgitation is easily missed on clinical examination, because it is soft and often short owing to the rapid equilibration of pulmonary artery diastolic pressure with the diastolic pressure in the right ventricle. It may be missed on echocardiography because of minimal turbulence and only small pressure differences between the right ventricle and the pulmonary artery. After pulmonary valvuloplasty the heart size should be normal on chest x-ray. A progressively increasing heart size should prompt the search for pulmonary regurgitation or another lesion. The development of atrial arrhythmias should also prompt a search for residual hemodynamic lesions such as pulmonary regurgitation.
Long-term follow-up data for percutaneous balloon pulmonary valvotomy are now available for up to 10 years. In one representative study (401), mean follow-up of 6.4 plus or minus 3.4 years was available in 62 patients. Some persistent pulmonary regurgitation was present in 39%, and the restenosis (greater than 35 mm Hg at follow-up) rate was only 4.8%. In a smaller study in adults (402) followed up for 4.5 to 9 years, no restenosis was reported in 24 patients after the gradient was reduced from 82 plus or minus 29 mm Hg to 37 plus or minus 14 mm Hg by the acute procedure. In another report of 127 adult patients without valve dysplasia, excellent results were also observed, with a residual gradient primarily found only in those patients who had an inadequate initial result (403). In the VACA registry (404), follow-up data were available on 533 patients a mean of 8.7 years after valvotomy. A suboptimal result (defined as gradient greater than 35 mm Hg at the end of the procedure) was present in 23%. Valve morphology and annulus size were the most significant predictors of long-term results. Pulmonary regurgitation was more commonly seen when the balloon-to-annulus ratio exceeded 1.4, which suggests an optimal ratio of 1.2 to 1.4. Subjective grades of pulmonary regurgitation reported included the following: none (26%), trivial (22%), mild (45%), moderate (7%), and severe (0%). Failure of the original procedure to reduce the gradient significantly also predicted poor long-term success. When restenosis does occur after percutaneous balloon pulmonary valvotomy, it appears that a repeat procedure is effective in patients without dysplastic pulmonary valves (405). Several studies have been reported that compared balloon valvotomy with matched surgical control patients (392,406,407).
In 1 study (406), gradients were slightly but statistically higher in the post–balloon valvotomy group than in the surgical cohort (24 plus or minus 2.7 versus 16 plus or minus 1.5 mm Hg). Pulmonary regurgitation, however, was absent (55%) or mild (45%) in the valvuloplasty group yet at least mild (45%) or moderate (45%) in the surgical cohort. Ventricular ectopy was also much more common in the surgical group (70% versus 5%). Thus, overall results were more favorable in the balloon valvotomy group.
Percutaneous balloon valvotomy thus appears to be an excellent alternative to surgical valvuloplasty or valve replacement in most patients with classic, doming, valvular PS. Its use in patients with a dysplastic valve is much less established, although several authors have suggested situations wherein it may be feasible (408,409). Postoperative valvular, conduit, or homograft stenosis contributes to the causes of clinical RVOT obstruction, with valvular degeneration expected after approximately 10 to 12 years (410). There are some data showing that porcine valves may outlast homografts in children (411). After surgical valvotomy, pulmonary regurgitation is common, and after 3 to 4 decades, RV dysfunction and secondary TR may ensue, necessitating pulmonary valve replacement in some patients. This should be undertaken before there is severe RV enlargement and any more than mild RV dysfunction. Deteriorating exercise capacity or the onset of atrial or ventricular arrhythmias is also a sign of the need for pulmonary valve replacement. This emphasizes the need for lifelong follow-up in such patients (412).
Pregnancy is well tolerated unless the lesion is extremely severe. Percutaneous valvotomy can be performed during pregnancy if necessary, although the need is unusual.
7.8.2. Endocarditis Prophylaxis
Pulmonary valve endocarditis is very rare, and endocarditis prophylaxis is not recommended (413) (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).
7.8.3. Exercise and Athletics
The 1986 AHA committee report (414) recommends no restriction of activity with mild PS and nonstrenuous exercise with moderate PS; it restricts only those with severe PS. For the competitive athlete, the special ACC Task Force report (415) recommends that PS patients with peak gradients less than 50 mm Hg may participate in all competitive sports, although those with more severe PS should participate only in low-intensity sports.
7.9. Right-Sided Heart Obstruction Due to Supravalvular, Branch, and Peripheral Pulmonary Artery Stenosis
7.9.1. Definition and Associated Lesions
Abnormal narrowing of the main pulmonary artery, the major pulmonary arterial branches, and the peripheral pulmonary arteries can all lead to obstruction of RV outflow. Supravalvular PS or pulmonary arterial stenosis is caused by narrowing of the main pulmonary trunk, the pulmonary arterial bifurcation, or the primary and/or intrapulmonary branches. One variant, the hourglass pattern, is similar to SupraAS and is technically a form of valvular PS, because it is due to stenosis at the commissural ridge of the valve (416). The other pulmonary supravalvular lesions are in the main branches or more peripheral and range from single focal lesions to diffuse hypoplastic ones to frank occlusion; they may be secondary to previous placement of a pulmonary artery band. The pulmonary arterial segments distal to patent stenotic lesions often exhibit poststenotic dilation. Membranous forms of obstruction both above and below the pulmonary valve have also been described. Central and peripheral pulmonary artery stenosis may be a major cardiovascular feature in the Alagille and Keutel syndromes (417–421). Pulmonary artery stenoses are also sequelae of the congenital Rubella syndrome, Williams syndrome, or scarring at the site of a previous pulmonary artery band or aorticopulmonary shunt. These lesions appear pathologically as areas of fibrous intimal proliferation with varying degrees of medial hyperplasia and loss of elastic fibers in the affected areas. The lesions can be single or multiple, and their severity can range from mild valvular stenosis to complete occlusion. Similar lesions have been reported in patients with systemic vasculitis, such as Behcet or Takayasu arteritis, and in patients with Ehlers-Danlos and Silver syndrome. Owing to the normally low vascular resistance present in the pulmonary circuit, a great deal of vascular obstruction is required to result in PAH. Despite the fact that it is unclear what severity of stenosis is truly flow-limiting in the pulmonary arteries, most clinicians define an angiographically significant lesion to be greater than 50% diameter narrowing. These significant lesions would be expected to have a pressure gradient across them and to result in hypertension in the more proximal pulmonary artery.
7.9.2. Clinical Course
Peripheral pulmonary artery stenoses tend to occur in multiple tertiary branches of the pulmonary tree and are progressive; by the time patients are seen as adults, there may be considerable loss of lung parenchyma due to totally occluded segmental pulmonary arteries. With PAH, pulmonary valve regurgitation may be expected.
7.10. Clinical Features and Evaluation of the Unrepaired Patient
The clinical symptom complex is similar to that of valvular PS. Dyspnea and chest pain are uncommon. In severe cases, RV dilation and associated TR may occur. Most patients seen in adulthood are patients referred for suspected primary PAH or chronic pulmonary thromboembolic disease. In the evaluation of a patient with suspected PAH, the presence of peripheral bruits over the back or on either lateral side of the chest during auscultation should raise the suspicion of peripheral PS. These pulmonary vascular bruits are usually systolic only but may be continuous and increase with inspiration. Cyanosis may appear if elevated right atrial pressures result in right-to-left shunting across a PFO.
Findings of certain syndromes should raise suspicion for the presence of pulmonary vessel stenotic lesions. The sequelae of the congenital Rubella syndrome consist of cataracts, deafness, hypotonia, retinopathy, dermatoglyphic abnormalities, and mental disability (422), and PS and peripheral PS are not uncommon.
The Alagille syndrome is an autosomal dominant disorder also called arteriohepatic dysplasia. The prominent features include deep-set eyes, a small pointed chin, and a prominent overhanging forehead (419). Abnormalities of the liver, heart, eyes, kidney, and skeleton occur, and peripheral PS frequently accompanies the disorder.
The Williams syndrome phenotype has micrognathia, a large mouth and lips, an upturned nose, hypertelorism, malformed teeth, broad forehead, and baggy cheeks (420). SupraAS coexists with peripheral PS.
The Keutel syndrome (423) consists of diffuse calcification of the cartilage, short stubby fingers (brachytelephalangism), hearing loss, and peripheral PS. It is a rare disorder believed to be autosomal recessive in its inheritance pattern.
ECG criteria for RV hypertrophy with strain and right-axis deviation are commonplace in the adult and are related to the severity of the lesion and the RV systolic pressure.
7.10.2. Chest X-Ray
The lung fields on chest x-ray may reveal varying shadows of poststenotic peripheral arterial dilatations in patients with peripheral PS.
TTE-Doppler helps confirm the presence of RV systolic hypertension and any pulmonary valve regurgitation. Echocardiography may also be able to define proximal pulmonary branch stenosis. It is of much less value in the identification of peripheral PS. TEE is likewise useful only when there are proximal pulmonary artery lesions. Radionuclide studies reveal the severity of peripheral PS in different lung segments.
7.10.4. Magnetic Resonance Imaging/Computed Tomography
Cardiac MRI with pulmonary angiography and CT are much superior to echocardiography-Doppler for imaging these lesions, and both can help confirm the diagnosis.
7.10.5. Cardiac Catheterization
Cardiac catheterization with contrast angiography is definitive and provides additional information regarding the extent of these lesions, the angiographic severity, the pressure drop across the lesions, and the degree of any associated PAH.
7.11. Recommendations for Evaluation of Patients With Supravalvular, Branch, and Peripheral Pulmonary Stenosis
1. Patients with suspected supravalvular, branch, or peripheral PS should have baseline imaging with echocardiography-Doppler plus 1 of the following: MRI angiography, CT angiography, or contrast angiography. (Level of Evidence: C)
2. Once the diagnosis is established, follow-up echocardiography-Doppler to assess RV systolic pressure should be performed periodically, depending on severity. (Level of Evidence: C)
7.11.1. Problems and Pitfalls
Patients with peripheral PS lesions may present with what appears to be a functional precordial murmur. Auscultation over the lung fields should reveal the characteristic vascular bruits. Many patients are asymptomatic. More often in adults, the patient presents with dyspnea of unknown origin. Elevated RV systolic pressure identified by echocardiography should prompt a search for causes of PAH that include collagen vascular disease, portal hypertension, human immunodeficiency virus, use of anorexigens, veno-occlusive disease, sleep apnea, chronic obstructive pulmonary disease, and sarcoidosis (424).
7.11.2. Management Strategies
22.214.171.124. Medical Therapy
Because these supravalvular lesions are mechanical obstructions, there are no effective medical therapies, except for the treatment of right-sided heart failure when it occurs. However, there are interventional therapies that may be attempted.
7.12. Recommendations for Interventional Therapy in the Management of Branch and Peripheral Pulmonary Stenosis
1. Percutaneous interventional therapy is recommended as the treatment of choice in the management of appropriate focal branch and/or peripheral pulmonary artery stenosis with greater than 50% diameter narrowing, an elevated RV systolic pressure greater than 50 mm Hg, and/or symptoms. (Level of Evidence: B)
2. In patients with the above indications for intervention, surgeons with training and expertise in CHD should perform operations for management of branch pulmonary artery stenosis not anatomically amenable to percutaneous interventional therapy. (Level of Evidence: B)
Branch pulmonary artery stenosis and/or hypoplasia may be associated with a variety of cardiac malformations or may be a residual from prior surgical intervention, such as an anastomotic lesion at the distal site of a prior Blalock-Taussig or Potts shunt procedure. Surgical exposure to these areas is often difficult, which favors attempts at percutaneous approaches. In some series, the acute success rate—defined as an increase of greater than 50% of predilation vessel diameter or a 20% decrease in systolic RV–to–aortic systolic pressure ratio (425)—has been as high as 60% initially. Complications have included arterial rupture, unilateral or segmental edema, thrombosis, and hemoptysis. In some instances, higher-pressure balloon inflations have improved results.
The highly elastic pulmonary arteries have proved resilient to balloon procedures, and angioplasty methods have generally given way to stent procedures in which there appears to be a higher initial success rate and a lower intermediate-term incidence of restenosis (426). When restenosis does occur, it may respond to redilation. Stents have proved effective compared with either percutaneous angioplasty or surgical intervention in this situation. Stenting of branch PS has also been used in the operating room as adjunctive therapy.
The use of balloon angioplasty and stenting may also be applied to more distal peripheral PS, although the results have generally been less impressive than with branch stenosis (427). Although initial angiographic results from stenting in this situation often appear encouraging, there are currently inadequate data to recommend the routine use of percutaneous intervention for patients with distal peripheral PS. Surgical intervention with patch enlargement is feasible for supravalvular PS when an oval patch is used (428), and more proximal branch stenosis may also be approached surgically if the vessel is of adequate size. More peripheral stenotic segments cannot usually be corrected with surgery. At times, the only alternative for patients with severe peripheral PS associated with major loss of lung parenchyma is lung transplantation.
7.12.1. Recommendations for Evaluation and Follow-Up
1. Patients with peripheral PS should be followed up every 1 to 2 years, on the basis of severity, with a clinical evaluation and echocardiography-Doppler to evaluate RV systolic pressure and RV function. (Level of Evidence: C)
2. Discussion with a cardiac surgeon with expertise in CHD should take place before percutaneous peripheral pulmonary artery interventions are undertaken. (Level of Evidence: C)
The lesions in peripheral PS may be progressive, so patients should be followed up every 1 to 2 years with echocardiography-Doppler to assess RV peak systolic pressure and function. If symptoms recur, then reimaging of the pulmonary arteries is required to assess whether restenosis has occurred and whether further intervention is feasible. Restenosis of these lesions is common, and repeat percutaneous angioplasty, stenting, or surgical intervention may be required when this occurs. When questions arise, consultation between the interventionalist and a congenital heart surgeon is necessary to determine the best approach.
7.13. Right-Sided Heart Obstruction Due to Stenotic Right Ventricular–Pulmonary Artery Conduits or Bioprosthetic Valves
7.13.1. Definition and Associated Lesions
Some gradient is to be expected across any RV–pulmonary artery conduit or any bioprosthetic valve placed in the RVOT. A variety of conduit types have been used in the RVOT, some with valvular tissue and some without. Pulmonary homografts have now come into widespread use, although bioprosthetic (porcine or pericardial) pulmonary valve replacements are still performed. Several groups have also reported experience with use of the valved bovine jugular venous conduit (Contegra), although some issues regarding stenosis at the distal pulmonary site have been noted (429). The normal gradient anticipated across the various prosthetic valves is dependent on the valve size and the flow across the valve. Associated pulmonary regurgitation increases the gradient. A recent review from the American Society of Echocardiography outlines the normally expected Doppler gradients for all prosthetic valves (430) and takes into account the type of valve and the size. Stenosis of the RV–pulmonary artery conduit or any bioprosthetic valve in this position may be graded with the peak Doppler gradient, with a 50-mm Hg gradient considered severe stenosis. This would be expected to result in an RV systolic pressure equal to or greater than 75 mm Hg. In children and young adults, a ratio of RV systolic to LV systolic pressure greater than 0.67 is another parameter for defining a severe lesion. In older adults, the systemic resistance is much higher than in children, and the use of this ratio has been less helpful.
7.13.2 Recommendation for Evaluation and Follow-Up After Right Ventricular–Pulmonary Artery Conduit or Prosthetic Valve
1. After surgical relief of RVOT obstruction with a conduit or prosthetic valve, patients should be followed up on a 1- to 2-year basis with echocardiography-Doppler assessment of RV systolic pressure and function, as well as a measurement of the gradient across the RVOT. (Level of Evidence: C)
7.13.3. Clinical Examination
A precordial systolic murmur that transmits to the back is an important sign of conduit obstruction. The pulmonary closure sound is usually inaudible. In patients with significant RV obstruction, jugular venous distension with a prominent A wave may be appreciated.
Because all bioprosthetic valves and conduit valves eventually degenerate, both pulmonary regurgitation and stenosis will ensue. As with many lesions that result in RV pressure or volume overload, the ECG may reflect RV hypertrophy or any associated arrhythmias.
7.13.5. Chest X-Ray
The chest x-ray may reveal an enlarging right side of the heart or calcification within the valve or conduit.
TTE and Doppler are particularly helpful in delineating hemodynamics and facilitate measurement of RV pressure, RV size and function, and gradient across the conduit and prosthetic valve; however, tubular narrowing in a conduit is often associated with underestimation of the gradient.
7.13.7. Magnetic Resonance Imaging/Computed Tomography
CT and MRI can be used to help define lesion severity and may demonstrate conduit adherence to the sternum, something of interest to the surgeon if a reoperation is contemplated.
7.13.8. Cardiac Catheterization
Because distal conduit stenosis is frequent, cardiac catheterization and angiography in addition to CT and MRI can define the level and severity of stenosis.
7.14. Recommendations for Reintervention in Patients With Right Ventricular–Pulmonary Artery Conduit or Bioprosthetic Pulmonary Valve Stenosis
1. Surgeons with training and expertise in CHD should perform operations for patients with severe pulmonary prosthetic valve stenosis (peak gradient greater than 50 mm Hg) or conduit regurgitation and any of the following:
a. Decreased exercise capacity. (Level of Evidence: C)
b. Depressed RV function. (Level of Evidence: C)
c. At least moderately enlarged RV end-diastolic size. (Level of Evidence: C)
d. At least moderate TR. (Level of Evidence: C)
1. Either surgical or percutaneous therapy can be useful in symptomatic patients with discrete RV–pulmonary artery conduit obstructive lesions with greater than 50% diameter narrowing or when a bioprosthetic pulmonary valve has a peak gradient by Doppler greater than 50 mm Hg or a mean gradient greater than 30 mm Hg. (Level of Evidence: C)
2. Either surgical or percutaneous therapy can be useful in asymptomatic patients when a pulmonary bioprosthetic valve has a peak Doppler gradient greater than 50 mm Hg. (Level of Evidence: C)
1. Surgical intervention may be considered preferable to percutaneous catheter intervention when an associated Maze procedure is being considered for the treatment of atrial arrhythmia. (Level of Evidence: C)
7.14.1. Medical Therapy
Medical management of symptomatic patients with residual or recurrent RVOT obstruction is limited to diuresis and is generally ineffective. There are no effective preventative treatments.
7.14.2. Interventional Catheterization
Both angioplasty and stenting have been applied to obstruction in an RV–to–pulmonary artery conduit. Such cases can present difficult issues, and the decision to proceed with a percutaneous intervention should be made in association with an ACHD surgeon or an ACHD interventionalist. Several investigators have reported success in reducing gradients in RV–to–pulmonary artery conduits or bioprostheses using balloon dilation (431,432), stenting, or percutaneous valve replacement (431–433). The value of these options often depends on whether a discrete obstruction occurs at the stenotic conduit valve or is the result of conduit compression between the sternum and heart, intimal peel formation, or obstruction at the ventricular anastomosis. Obstruction of the distal end of the conduit may be amenable to percutaneous balloon intervention in which the procedure may be useful as a temporary palliation that allows postponement of surgical intervention (434).
A potential alternative to either balloon dilation or stenting in conduit obstruction has been presented recently by Bonhoeffer et al (435), wherein pulmonary valves have been implanted percutaneously within the stenotic conduit. The authors used a bovine jugular venous valve mounted onto a balloon-expandable stent for percutaneous placement. Although the procedure is investigational, it appears quite possible that this approach will evolve to provide an excellent option for the therapy of conduit stenosis and regurgitation. The procedural concept has yet to be proven in larger clinical trials and has yet to be shown to be effective in patients with native valvular PS or regurgitation.
7.14.3. Surgical Intervention
Surgical intervention is generally required once there is evidence of important RV enlargement or the development of significant TR. Because of the complexity of these procedures at times, surgical intervention should be done by a team with specific expertise in ACHD issues.
7.14.4. Key Issues to Evaluate and Follow-Up
Most patients are not limited physically unless the gradient across the conduits or prosthetic valves is greater than 50 mm Hg. Pregnancy is well tolerated unless RV failure is a major issue. Much as with postprocedural valvular PS, the degree of obstruction and the severity of the pulmonary regurgitation determine the frequency of follow-up and the necessary studies. For asymptomatic patients with RV pulmonary artery conduits (with or without a valve) and for those with prosthetic pulmonary valves, regular follow-up with echocardiography-Doppler is usually sufficient. Endocarditis prophylaxis is recommended for patients with a prosthetic pulmonary valve or conduit (refer to Section 1.6, Recommendations for Infective Endocarditis).
7.15. Double-Chambered Right Ventricle
7.15.1. Definition and Associated Lesions
In patients with a double-chambered right ventricle, the right ventricle is divided into a higher-pressure proximal chamber and lower-pressure distal chamber by anomalous myocardial muscle bundles. The morphological features may be very diverse and may involve an anomalous septoparietal band, an anomalous apical shelf, or an abnormal moderator band (376). The distance between the moderator band and the pulmonary artery may be abnormally short (436).
Although the anatomic substrate is congenital, the degree of RVOT obstruction is progressive over time. In approximately three fourths of cases, the VSD is below (proximal to) the level of the midventricular obstruction. Complete or partial spontaneous closure of the VSD can produce worsening RV outflow obstruction and dysfunction. Other associations include valvular PS, tetralogy of Fallot, and double-outlet right ventricle. Unlike tetralogy of Fallot, there is also subaortic obstruction in a number of these patients. The anomaly is uncommon and occurs in approximately 1% of patients with CHD (437). No genetic pattern has been identified, although it has been reported to develop in approximately 3% of patients with repaired tetralogy of Fallot and 3% to 10% of patients with an isolated VSD (438,439).
7.15.2. Clinical Features and Evaluation of the Unoperated Patient
Although most patients undergo repair before adulthood, some present much later. Symptoms in the adult may mimic coronary disease (angina) or LV dysfunction (dyspnea). Occasionally, dizziness and syncope may occur. Some patients are recognized because of the increasing intensity of a systolic murmur, previously ascribed to a small VSD or functional murmur.
7.15.3. Clinical Examination
If midventricular obstruction is marked, the resulting hypertrophy results in an RV heave, and the murmur across the obstruction is harsh, increases with inspiration, and may be accompanied by a palpable thrill. The murmur of an associated VSD may be evident if present. If there is an associated interatrial connection, or the VSD is proximal to the obstruction, cyanosis may occur. Rarely, RV failure and TR develop as the obstruction progresses. In 1 study of patients without repair, the midventricular gradients increased an average of 6.2 plus or minus 3 mm Hg each year (440).
The ECG usually suggests RV hypertrophy. Right-sided leads may help confirm the diagnosis, with upright T waves in V3R in 40% of the patients tested (441).
7.15.5. Echocardiography-Doppler Imaging
The TTE is diagnostic, with demonstration of the hypertrophy and Doppler/color flow evidence of midventricular gradient. The VSD may be noted. TEE is not usually necessary for the diagnosis.
7.15.6. Magnetic Resonance Imaging
In addition to TTE, MRI is the most useful imaging modality for defining the anatomy (442).
7.15.7. Cardiac Catheterization
Cardiac catheterization and angiography are confirmatory and provide relevant imaging and hemodynamic and shunt information but are rarely necessary to establish the diagnosis.
7.16. Problems and Pitfalls
7.16.1. Multiple Levels of Right Ventricular Outflow Tract Obstruction
As noted previously, RVOT obstruction can occur at multiple levels that can exist simultaneously. The peak RV systolic pressure, as estimated by echocardiography-Doppler via the TR jet, may be the result of more than 1 level of obstruction; therefore, it is important to investigate this possibility thoroughly before surgical intervention is considered. This is particularly important in the adult, in whom prior surgical procedures and other causes of PAH may complicate the clinical picture.
7.17. Management Strategies
7.17.1. Recommendations for Intervention in Patients With Double-Chambered Right Ventricle
1. Surgery is recommended for patients with a peak midventricular gradient by Doppler greater than 60 mm Hg or a mean Doppler gradient greater than 40 mm Hg, regardless of symptoms. (Level of Evidence: B)
1. Symptomatic patients with a peak midventricular gradient by Doppler greater than 50 mm Hg or a mean Doppler gradient greater than 30 mm Hg may be considered for surgical resection if no other cause of symptoms can be discerned. (Level of Evidence: C)
Echocardiography or cardiac MRI should be used for follow-up. In patients with anginal symptoms, cardiac catheterization to exclude coronary disease may be warranted. Because there may be some dynamic obstruction contributing to the gradient, beta blockers and calcium channel blockers may be tried, but there are few data as to the effectiveness of any medical intervention, and significant (greater than 60-mm Hg peak Doppler gradient) stenosis should be treated with surgical resection.
Isolated case reports of the use of percutaneous balloon techniques, stenting, and alcohol ablation have been reported in patients with subvalvular fibromuscular obstruction, with variable success (443–445). Alcohol ablation of a feeding RV conus branch artery was reported to result in a reduction in the outflow tract gradient. Stenting may also prove to be effective, although stent fracture may occur (446), which raises concerns about stent integrity in the contracting RVOT. Currently, there are no follow-up or comparative results available to suggest any of these percutaneous options are preferable to a surgical approach in these patients.
In patients with double-chambered right ventricle, resection and outflow-enlarging procedures have been very effective, with excellent long-term results (447). Many also require repair of an associated VSD.
7.18. Key Issues to Evaluate and Follow-Up
Most patients do well after surgical intervention of the midventricular obstruction and have few physical limitations. The recurrence of obstruction after adequate surgical repair is quite rare, and follow-up of associated congenital defects usually takes precedence when these patients are reevaluated. There are case reports of patients developing a double-chambered RV after repair of either tetralogy of Fallot (438) or a perimembranous VSD (448). Activity is usually unlimited after surgery. Endocarditis prophylaxis is not recommended (refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information).
8. Coronary Artery Abnormalities
8.1. Definition and Associated Lesions
This section includes discussion of patients with acquired coronary anomalies as a result of surgical manipulation of their congenital anomaly, as well as those patients with congenital coronary abnormalities associated with ectopic origins of the coronary arteries.
8.1.1. General Recommendations for Evaluation and Surgical Intervention
1. Any patient with CHD who has had coronary artery manipulation should be evaluated for coronary artery patency, function, and anatomic integrity at least once in adulthood. (Level of Evidence: C)
2. Surgeons with training and expertise in CHD should perform operations for the treatment of coronary artery anomalies. (Level of Evidence: C)
Surgical results after the use of reconstruction of the coronary ostium or bypass grafting, depending on anatomy of the lesions noted, have been described, without long-term follow-up (365). In addition to the more commonly noted coronary abnormalities described elsewhere in this section, late development of coronary artery disease that requires revascularization (percutaneous or surgical) has been shown to occur after the Ross procedure, aortic and pulmonary atresia, and Kawasaki disease (449).
8.2. Recommendations for Coronary Anomalies Associated With Supravalvular Aortic Stenosis
1. Adults with a history or presence of SupraAS should be screened every 1 or 2 years for myocardial ischemia. (Level of Evidence: C)
2. Interventions for coronary artery obstruction in patients with SupraAS should be performed in ACHD centers with demonstrated expertise in the interventional management of these patients. (Level of Evidence: C)
Although SupraAS may be the least common of the lesions of the LV outflow, lesions may be associated with coronary obstruction from partial to complete ostial obliteration, and patients with these lesions are also at risk for ectasia and aneurysm of the coronary arteries (360). Pathological specimens with diffuse or focal intimal and medial fibrosis, hyperplasia, dysplasia, adventitial fibroelastosis, and occasional intramedial dissection have been reported in children and more commonly in adults (361–363).
8.2.1. Clinical Course (Unrepaired)
Clinical presentation with ischemic symptomatology referable to insufficient coronary artery flow has been reported due to either anatomic obstruction or myocardial hypertrophy that limits nonepicardial coronary flow (364).
8.2.2. Clinical Features
There are no current data describing the incidence of coronary artery symptomatology or outcomes in adults with SupraAS. Nonetheless, given the similarity of pathology to other diffuse coronary arteriopathies, the present writing committee would recommend noninvasive screening for myocardial ischemia in all adults with SupraAS, regardless of repair status. If further definition of coronary artery anatomy were suggested, other imaging modalities such as cardiac catheterization, CT angiography, or intravascular ultrasonography might better define the nature and extent of diseased vessel before consideration of repair.
8.3. Recommendation for Coronary Anomalies Associated With Tetralogy of Fallot
1. Coronary artery anatomy should be determined before any intervention for RV outflow. (Level of Evidence: C)
Abnormalities seen in CHD include single coronary artery, coronary arteriovenous fistula, intramural coronary artery, supravalvular ridge, accessory left anterior descending coronary artery, and anomalous coronary artery from the pulmonary artery. The most common and important abnormality is the left anterior descending coronary artery arising from the right coronary artery and crossing the RV outflow, which occurs in approximately 3% to 7% of persons with tetralogy of Fallot. The occurrence is more common when the aortic root is more anterior, rightward, or lateral (450).
Given the remarkable survival of adults with tetralogy, it is not of surprise that occurrence of atherosclerotic coronary artery disease has been described (451).
8.3.1. Preintervention Evaluation
Coronary artery origin and course should be delineated before any surgical or interventional procedure, because the potential exists for damage to anomalous coronary arteries to occur during cardiac exposure, surgery on the RVOT, and stenting of RV outflow.
8.3.2. Surgical and Catheterization-Based Interventions
Coronary artery bypass and percutaneous coronary interventions for occurrence of atherosclerotic disease in adults with tetralogy of Fallot have been described (451).
8.4. Recommendation for Coronary Anomalies Associated With Dextro-Transposition of the Great Arteries After Arterial Switch Operation
1. Adult survivors with dextro-TGA (d-TGA) after ASO should have noninvasive ischemia testing every 3 to 5 years. (Level of Evidence: C)
8.4.1. Definition and Associated Lesions
The coronary artery course plays an important role in the surgical repair of d-TGA. The most common anatomic arrangement occurs in nearly two thirds of patients, with the left coronary artery arising from the anterior facing sinus and the right coronary artery from the posterior facing sinus. Sixteen percent of patients with d-TGA have a circumflex that arises from the right coronary artery, and the remaining patients have inverted coronary artery variants, single coronary arteries, or intramural coronary arteries (452). Damage to the sinus node coronary artery, whether during surgery or during balloon septostomy, has been implicated in the occurrence of atrial arrhythmias and sinus node dysfunction after repair.
8.4.2. Clinical Course
After great artery translocation and transfer of coronary arteries, early and late postoperative loss of coronary perfusion may occur due to causes such as anatomic torsion, extrinsic compression, focal or diffuse fibrocellular intimal thickening, and small-caliber distal coronary arteries with functional decrease in coronary flow reserve (453–455). Survival free of coronary events has been reported as 93% and 88% at 1 and 15 years, respectively, with many reports associating coronary events with increased mortality (455).
8.4.3. Clinical Features and Evaluation After Arterial Switch Operation
No single ischemia provocation test has been shown to be both sufficiently sensitive and specific to screen for coronary flow abnormalities after a switch repair of d-TGA, and combinations of testing, including echocardiography, nuclear scintigraphy, and exercise testing, have been suggested to improve sensitivity and specificity (455). Given the emergence of an adult population of survivors with d-TGA after ASO, with undefined future course and morbidity, the present writing committee recommends episodic noninvasive ischemia provocation testing every 3 to 5 years. Positive results should be pursued by invasive catheterization with measurement of coronary flow reserve and intravascular ultrasound when appropriate.
8.4.4. Surgical and Catheterization-Based Intervention
Successful surgical, balloon angioplasty, and catheter-based stent revascularizations have been reported after ASO repair for d-TGA (456–458). We recommend that obstructive lesions with associated ischemia or flow abnormalities undergo revascularization appropriate to the lesion.
8.5. Recommendations for Congenital Coronary Anomalies of Ectopic Arterial Origin
1. The evaluation of individuals who have survived unexplained aborted sudden cardiac death or with unexplained life-threatening arrhythmia, coronary ischemic symptoms, or LV dysfunction should include assessment of coronary artery origins and course. (Level of Evidence: B)
2. CT or magnetic resonance angiography is useful as the initial screening method in centers with expertise in such imaging. (Level of Evidence: B)
3. Surgical coronary revascularization should be performed in patients with any of the following indications:
a. Anomalous left main coronary artery coursing between the aorta and pulmonary artery. (Level of Evidence: B)
b. Documented coronary ischemia due to coronary compression (when coursing between the great arteries or in intramural fashion). (Level of Evidence: B)
c. Anomalous origin of the right coronary artery between aorta and pulmonary artery with evidence of ischemia. (Level of Evidence: B)
1. Surgical coronary revascularization can be beneficial in the setting of documented vascular wall hypoplasia, coronary compression, or documented obstruction to coronary flow, regardless of inability to document coronary ischemia. (Level of Evidence: C)
2. Delineation of potential mechanisms of flow restriction via intravascular ultrasound can be beneficial in patients with documented anomalous coronary artery origin from the opposite sinus. (Level of Evidence: C)
1. Surgical coronary revascularization may be reasonable in patients with anomalous left anterior descending coronary artery coursing between the aorta and pulmonary artery. (Level of Evidence: C)
8.5.1. Definition, Associated Lesions, and Clinical Course
Congenital anomalous origin of the coronary arteries may occur in 1% to 1.2% of all coronary angiograms performed, with 0.5% of them having the highest-risk lesions of the left main or left anterior descending branch artery arising from the opposite sinus of Valsalva (459). Coronary anomalies account for approximately 15% of sudden cardiac deaths in athletes (potentially due to torsion or slitlike compression of the proximal coronary artery, exercise-induced compression, vasospasm, or ischemic or scar-induced ventricular arrhythmia) (460,461). In 80% of autopsies in athletes with sudden cardiac death and anomalous coronary artery origins, the affected coronary artery coursed between the aorta and the pulmonary artery (461,462).
8.5.2. Clinical Features and Evaluation of the Unoperated Patient
126.96.36.199. Preintervention Evaluation
Patients may present with aborted sudden death, chest pain, arrhythmia, LV dysfunction, or exercise-induced presyncope or syncope. Recently, clinical ischemia provocation screening has been suggested to reduce the global risk of sudden cardiac events in high-risk competitive sports populations; however, individual case reports in which such testing failed to reveal at-risk abnormalities in athletes who later succumbed to sudden coronary death due to anomalous coronary origins highlight the need for further improvement in screening strategies. Visualization of coronary artery course is achieved by CT or MRI (463,464).
To date, anatomic delineation of a coronary artery course between the aorta and pulmonary artery in a young (less than age 50 years) person remains the greatest known risk for an adverse event, with or without symptoms (319). Catheter-based measurement of flow reserve and coronary intravascular ultrasonography have the potential to delineate mechanisms of potential flow obstruction and are increasingly part of diagnostic and therapeutic algorithms (459,465). At present, especially in those younger than age 50 years, this writing committee recommends coronary CT or MRI for more definitive definition of coronary course in persons suspected of having anomalous coronary origins.
8.5.3. Management Strategies
188.8.131.52. Surgical and Catheterization-Based Intervention
Both surgical revascularization (eg, marsupialization, coronary bypass, or coronary reimplantation) and limited cases of transcatheter stenting have been reported to have short-term stability, without long-term follow-up (466). Coronary bypass grafting is increasingly viewed as a less favorable approach in light of the potential for competitive flow (467).
Surgical revascularization in centers with expertise in the surgical management of anomalous coronary arteries is suggested (319,462,468). Surgical repair is indicated when the left coronary arteries arise from the opposite sinus and course between the aorta and pulmonary artery. Surgical repair is also indicated when the right coronary artery arises from the opposite sinus or courses between the aorta and pulmonary artery in association with concomitant symptoms, or when there is evidence of otherwise unexplained inducible ischemia in these territories (469,470). When the patient has an anomalous right coronary artery and no evidence of ischemia, management is more controversial. A conservative approach in this situation may be reasonable. Given the not uncommon occurrence of anomalous coronary origins and their potential for a devastating outcome, it is imperative that improved data are generated regarding diagnosis, follow-up, and longer-term outcomes.
8.6. Recommendations for Anomalous Left Coronary Artery From the Pulmonary Artery
1. In patients with an anomalous left coronary artery from the pulmonary artery (ALCAPA), reconstruction of a dual coronary artery supply should be performed. The surgery should be performed by surgeons with training and expertise in CHD at centers with expertise in the management of anomalous coronary artery origins. (Level of Evidence: C)
2. For adult survivors of ALCAPA repair, clinical evaluation with echocardiography and noninvasive stress testing is indicated every 3 to 5 years. (Level of Evidence: C)
8.6.1. Definition and Associated Lesions and Clinical Course
ALCAPA is relatively rare, occurring in 1 in 300 000 live births. Improved operative revascularization, ensuing myocardial remodeling, and improved medical management of heart failure have increased survival after ALCAPA repair. Similarly, these improvements in care and the recognition of hibernating myocardium have increased the survival of adults with ALCAPA (471). Most adults survive because of collaterals from the right coronary artery, but they may have myocardial ischemia, LV dysfunction, mitral regurgitation, or ventricular arrhythmia. The transition from single to dual coronary surgical repair was performed first by a Takeuchi intrapulmonary arterial baffle; since then, coronary artery reimplantation or coronary bypass grafting has been used for repair (472).
Suprapulmonary arterial stenosis, baffle leaks, and baffle stenosis have all been reported after Takeuchi baffle repair. Late postrepair AR and residual significant mitral valve disease have both been reported. Chest pain, nuclear and positron emission tomography myocardial perfusion abnormalities, and decreased exercise performance have been noted after dual coronary artery repair and may correlate with residual patchy myocardial fibrosis from preoperative ischemia, as well as from residual proximal graft obstruction (473–476). Proximal, midvessel, and even distal coronary artery obstructions, with coronary flow reserve abnormalities, have been noted and treated with intracoronary balloon dilations, stenting, radiotherapy, and reoperation (477–480). There has been no consistent correlation between long-term outcome and late symptoms, noninvasive ischemia and blood flow abnormality testing, residual coronary anatomic or flow abnormalities, or late interventions.
8.7. Management Strategies
8.7.1. Surgical Intervention
If patients present in adulthood with decreased systolic function and previously unrecognized ALCAPA, the present writing committee suggests surgical myocardial revascularization to achieve a dual coronary supply, regardless of myocardial viability testing, given the lack of current data to correlate such testing with outcomes. Given the increasing awareness of residual coronary artery, myocardial, and valvular abnormalities, the present writing committee suggests surveillance with echocardiography and noninvasive ischemia provocation testing every 3 to 5 years for patients after repair of ALCAPA.
8.7.2. Surgical and Catheterization-Based Intervention
Surgical repair by either arterial bypass or, more commonly, reimplantation of the anomalous coronary into the aorta is indicated because of the risk of sudden cardiac death (481,482). If ischemia is demonstrated in patients after repair of ALCAPA with either concomitant symptomatology or echocardiographic changes, the present writing committee recommends invasive catheterization with planned intervention determined by clinical findings.
8.8. Recommendations for Coronary Arteriovenous Fistula
1. If a continuous murmur is present, its origin should be defined either by echocardiography, MRI, CT angiography, or cardiac catheterization. (Level of Evidence: C)
2. A large CAVF, regardless of symptomatology, should be closed via either a transcatheter or surgical route after delineation of its course and its potential to fully obliterate the fistula. (Level of Evidence: C)
3. A small to moderate CAVF in the presence of documented myocardial ischemia, arrhythmia, otherwise unexplained ventricular systolic or diastolic dysfunction or enlargement, or endarteritis should be closed via either a transcatheter or surgical approach after delineation of its course and its potential to fully obliterate the fistula. (Level of Evidence: C)
1. Clinical follow-up with echocardiography every 3 to 5 years can be useful for patients with small, asymptomatic CAVF to exclude development of symptoms or arrhythmias or progression of size or chamber enlargement that might alter management. (Level of Evidence: C)
1. Patients with small, asymptomatic CAVF should not undergo closure of CAVF. (Level of Evidence: C)
The development of epicardial and intramural coronary arteries has recently become better understood, with increasing awareness of the vasculogenesis involved in regulation of cell fate, cell migration, transition, and patterning (483). Nonetheless, the present writing committee still has a very primitive understanding of CAVF occurrence and long-term outcomes. The incidence is 0.1% to 0.2% of all catheterized patients, second in frequency of all coronary artery congenital abnormalities to anomalous origin of the coronary arteries (484). Fistulas arise from either or both coronary arteries, with drainage more typically to the right atrium, right ventricle, or right atrial–superior vena cava junction, and occasionally to the coronary sinus or left side of the heart.
8.8.2. Clinical Course
Although the potential for associated myocardial ischemia and infarction, endarteritis, dissection, and rupture has been documented, there are few data associating occurrence, shunt properties, anatomic features, and outcomes. Increasing fistula and shunt size may be associated with increased abnormalities of coronary flow and complications that include chest pain, decreased life expectancy, and risk of rupture (485). Small fistulas may slowly increase in size with advancing age and changes in systemic blood pressure and aortic compliance. Periodic clinical evaluation with imaging such as echocardiography to assess both the size of the fistula and ventricular function is reasonable. Sometimes, small fistulas are detected as an incidental finding on echocardiography.
8.8.3. Preintervention Evaluation
Transcatheter delineation of the CAVF course and access to distal drainage should be performed in all patients with audible continuous murmur and recognition of CAVF.
8.9. Recommendations for Management Strategies
1. Surgeons with training and expertise in CHD should perform operations for management of patients with CAVF. (Level of Evidence: C)
2. Transcatheter closure of CAVF should be performed only in centers with expertise in such procedures. (Level of Evidence: C)
3. Transcatheter delineation of CAVF course and access to distal drainage should be performed in all patients with audible continuous murmur and recognition of CAVF. (Level of Evidence: C)
8.9.1. Surgical Intervention
Surgical fistula closure can be successful if CAVF is well defined and clear surgical access is believed to be technically achievable. Recurrence may be a problem if anatomic definition is suboptimal, and surgery may be difficult to perform owing to poorly visualized, typically distal fistulous connections. Surgical closure of audible CAVF with appropriate anatomy is recommended in all large CAVFs and in small to moderate CAVFs in the presence of symptoms of myocardial ischemia, threatening arrhythmia, unexplained ventricular dysfunction, or left atrial hypertension.
8.9.2. Catheterization-Based Intervention
Numerous reports of transcatheter closure with coils or detachable devices describe near or complete CAVF occlusion in attempted closure procedures (486). Criteria for transcatheter closure of CAVF are similar to those used for surgical closure of CAVF. Transcatheter closure of CAVF should be performed only in centers with particular expertise in such intervention.
8.9.3. Preintervention Evaluation After Surgical or Catheterization-Based Repair
Patients with CAVF, even after repair, may still have large, patulous epicardial conduits. Intermediate- and longer-term follow-up of these thin-walled, ectatic coronary arteries after either surgical or transcatheter repair appears mandated.
9. Pulmonary Hypertension/Eisenmenger Physiology
PAH, a progressive increase in PVR, can lead to subpulmonary ventricular failure and death. PAH can frequently be related to pulmonary venous hypertension (most commonly due to left AV valve disorders, volume excess, or systemic ventricular end-diastolic pressure elevation) and can be classified as World Health Organization PAH class II (due to “left heart disease”) with therapies guided toward improving these causes. Within this section, however, the present writing committee will primarily focus on disorders in which PAH is due to other abnormalities and is generally hemodynamically defined as a mean pulmonary artery pressure greater than 25 mm Hg at rest or greater than 30 mm Hg with exercise, pulmonary capillary wedge pressure less than or equal to 15 mm Hg, and PVR greater than 3 mm Hg per L per min per m2. Idiopathic PAH or PAH of unclear relationship to other diseases is typically a diagnosis of exclusion within the World Health Organization (group I PAH), according to a classification scheme similar to the World Health Organization clinical classification (424). Additional “triggers” for the development of PAH may be present at increased rates in patients with CHD compared with nonaffected individuals. These triggers include but are not restricted to parenchymal and restrictive lung disease, hypoventilation, high altitude, genetic predispositions such as Down syndrome, and left atrial or pulmonary venous hypertension or obstruction. Particular CHD-related PAH (CHD-PAH) occurs in a number of different scenarios, including the following:
a. “Dynamic” PAH related to high shunt flow that responds to reduction of the shunt
b. Immediate postoperative or “reactive” PAH
c. Late, postoperative PAH
d. Secondary to lesions that cause pulmonary venous hypertension
e. Shunt reversal (eg, Eisenmenger physiology).
These guidelines will largely focus on the management of dynamic PAH and Eisenmenger physiology. Recently, CHD-PAH has been recognized to have potentially differing pathogenetic mechanisms, therapeutic goals, treatment plans, and outcomes compared with idiopathic PAH. Hence, during the Third World Symposium on Pulmonary Arterial Hypertension, CHD-PAH was categorized as a unique entity within the more global PAH categorization (group I) (424). Subcategories were also designated on the basis of the complexity and size of the defect, its association with additional extracardiac anomalies, and the status of anatomic repair. More recently, an expansion of the subcategorization has been proposed that allows for further classification based on anatomy (defects above and below the tricuspid valve, as well as clarification of specific types of complex disease), the presence of myocardial restriction (as evidenced by equalization of pressure between chambers), and direction of shunt (left to right, right to left, or balanced) (487).
Congenital heart defects that can lead to PAH are numerous. Unrepaired, large systemic–to–pulmonary artery (left-to-right) shunts, seen in ASD, VSD, AVSD, and PDA, account for most cases of PAH. However, complex lesions such as partial or total anomalous pulmonary venous return, unrepaired or palliated conoventricular defects including truncus arteriosus, or transposition of the great arteries, and single-ventricle variants can also result in the development of PAH. Other causes of PAH may include pulmonary vein stenosis and pulmonary veno-occlusive disease. Over time, with severe vascular changes accompanying a persistent large anatomic shunt, a bidirectional or predominantly right-to-left shunt accompanied with oxygen-unresponsive hypoxemia can ensue, identified as Eisenmenger physiology (488). In patients with large left-to-right shunts or unrepaired complex congenital heart defects, PAH can develop as early as the first decade of life; however, in patients with medium-sized or larger ASDs, Eisenmenger syndrome typically appears later in life and may be recognized first during the changes in hemodynamic loading that occur with pregnancy. Whether additional triggers of PAH other than intravascular shunts are required for development of Eisenmenger syndrome remains debatable.
9.2. Clinical Course
9.2.1. Dynamic Congenital Heart Disease–Pulmonary Arterial Hypertension
The development of CHD-PAH associated with systemic–to–pulmonary artery shunts is dependent on both the type and size of the underlying anatomic defect, as well as the magnitude of shunt flow (shear stress and structural changes lead to intravascular and matrix-dependent inflammatory mediator release and changes). Pulmonary vascular histology resembles that described in idiopathic PAH, with medial thickening and plexiform lesions in severe cases (489). In fact, the hypertensive pulmonary arteriopathy, vasoconstriction, and marked increase in pulmonary ventricular afterload of CHDs was the first model used to assist in the understanding of the vascular and cardiac changes associated with idiopathic PAH (490).
Individuals with an unrepaired truncus arteriosus are at very high risk of developing PAH, whereas those with VSDs and ASDs are at moderate and relatively low risk, respectively. Whether the variation in these risks is related to shunt flow or to an underlying genetic predisposition is unknown. The nature of the anatomic abnormality also determines the age at presentation. Patients with AVSD, truncus arteriosus, transposition of the great vessels, large PDA, and VSD present earliest. Most patients with CHD-PAH have a better prognosis than those with idiopathic PAH.
9.2.2. Immediate Postoperative Congenital Heart Disease–Pulmonary Arterial Hypertension
More commonly reported in children than in ACHD patients, pulmonary vascular reactivity due to perioperative endothelial cell injury may be heightened in the immediate postoperative phase of cardiopulmonary surgery. This can precipitate marked increases in PVR, leading to acute right-sided heart failure with the attendant decrease in cardiac output, systemic hypotension, metabolic acidemia, and right-sided heart ischemia. In addition, airway resistance increases in relation to peribronchial edema and bronchoconstriction, gas exchange suffers, and alveolar edema and cardiovascular collapse may occur in the final stages. Immediate perioperative acute increases in pulmonary resistance that precipitate a “crisis” tend to occur in individuals with more “dynamic” and less “fixed” resistance.
9.2.3. Late Postoperative Congenital Heart Disease–Pulmonary Arterial Hypertension
Typically, late postoperative CHD-PAH is attributed to the timing of anatomic shunt repair that is too late, miscalculation of the likelihood of surgical repair, or the long-standing effects of stable but elevated RV afterload that leads to recalcitrant vascular remodeling. However, when one diagnoses late postoperative CHD-PAH, the multiple additional non–shunt-mediated risk factors (including LV hypertrophy and diastolic dysfunction, valvular abnormalities, pulmonary venous hypertension or obstruction, restrictive or hypoventilatory lung disease, chronic liver disease, and toxin use) that contribute to PAH must be ruled out to target appropriate therapy.
9.2.4. Normal to Mildly Abnormal Pulmonary Vascular Resistance States
Individuals with tricuspid atresia or similar single-ventricle physiologies who undergo surgical creation of cavopulmonary anastomoses (Glenn shunt and its variants or Fontan palliation and its variants) have pulmonary circulation that connects directly to the systemic venous circulation, lacks normal pulsatile flow, and hence depends on low PVR for survival. Because the subpulmonary ventricle has been bypassed, and circulation of blood relies solely on systemic ventricular function, any increase in pulmonary vascular impedance can interfere with LV filling. Thus, maintenance of a low PVR is critically important. Clinical course and further management strategies are discussed elsewhere in these guidelines.
9.2.5. Eisenmenger Physiology
Similar to patients with idiopathic PAH, dyspnea on exertion is the most common presenting symptom of patients with Eisenmenger physiology, followed by palpitation, edema, volume retention, hemoptysis, syncope, and progressive cyanosis (488). Increasingly through the third decade of life, morbidity becomes substantial in this patient population. Eisenmenger patients have additional complications compared with patients with idiopathic or other forms of secondary PAH. Hypoxemia-related secondary erythrocytosis leads to increased blood viscosity and intravascular sludging worsened by associated iron deficiency. Organ damage may result, predominantly noted in cerebrovascular changes from sludging, stroke, and alterations in renal function. Hyperpnea may also occur. Right-sided volume overload and elevated systemic venous pressure may lead to changes in hepatic function. Hyperuricemia may result in gout. Hemoptysis remains a potential threat to life when severe; the occurrence of other clinical bleeding disorders is a matter of debate. Concomitant congenital skeletal abnormalities and restrictive lung disease may worsen hypoxemia. True cardiac ischemic chest pain due to RV ischemia, coronary artery compression by a dilated pulmonary artery, or atherosclerosis may occur with exertion or at rest. Progressive subpulmonary ventricular failure and premature death are the rule in adults with Eisenmenger syndrome, with immediate causes of death including pulmonary ventricular failure, severe hemoptysis from bronchial artery rupture or pulmonary infarction, complications during pregnancy, and cerebral vascular events, including occlusive strokes, systemic paradoxical embolization, and brain abscesses (264,491,492). Death during noncardiac surgery also occurs. Poor functional class is a significant predictor of mortality for Eisenmenger patients, as are serological evidence of low systemic organ perfusion, worsened hypoxemia, and LV systemic dysfunction (493).
9.3. Problems and Pitfalls
Below are the problems and pitfalls in the diagnosis and management of ACHD-related PAH.
• Patients with severe ACHD-related PAH do not have loud murmurs on auscultation because the RV pressure is similar to the LV pressure. In such patients, associated anomalies such as PS should be excluded.
• All potential triggers for PAH, including noncongenital cardiac triggers, should be sought. Therapies for noncongenital triggers should be maximized.
• Diagnosis and therapy hinge on accurate and definitive cardiac catheterization. Additional imaging modalities are often of assistance.
• Oxygen-responsive hypoxemia may occur and should be treated.
• Pregnancy is contraindicated in women with CHD-PAH.
9.4. Recommendations for Evaluation of the Patient With Congenital Heart Disease–Pulmonary Arterial Hypertension
1. Care of adult patients with CHD-related PAH should be performed in centers that have shared expertise and training in both ACHD and PAH. (Level of Evidence: C)
2. The evaluation of all ACHD patients with suspected PAH should include noninvasive assessment of cardiovascular anatomy and potential shunting, as detailed below:
a. Pulse oximetry, with and without administration of supplemental oxygen, as appropriate. (Level of Evidence: C)
b. Chest x-ray. (Level of Evidence: C)
c. ECG. (Level of Evidence: C)
d. Diagnostic cardiovascular imaging via TTE, TEE, MRI, or CT as appropriate. (Level of Evidence: C)
e. Complete blood count and nuclear lung scintigraphy. (Level of Evidence: C)
3. If PAH is identified but its causes are not fully recognized, additional testing should include the following:
a. Pulmonary function tests with volumes and diffusion capacity (diffusing capacity of the lung for carbon monoxide). (Level of Evidence: C)
b. Pulmonary embolism–protocol CT with parenchymal lung windows. (Level of Evidence: C)
c. Additional testing as appropriate to rule out contributing causes of PAH. (Level of Evidence: C)
d. Cardiac catheterization at least once, with potential for vasodilator testing or anatomic intervention, at a center with expertise in catheterization, PAH, and management of CHD-PAH. (Level of Evidence: C)
1. It is reasonable to include a 6-minute walk test or similar nonmaximal cardiopulmonary exercise test as part of the functional assessment of patients with CAD-PAH. (Level of Evidence: C)
9.4.1. Dynamic Congenital Heart Disease–Pulmonary Arterial Hypertension
Surgical experience has suggested that the changes that occur with shunt-mediated PAH are reversible, provided the surgery is performed before pulmonary vascular changes are “fixed.” Catheterization-based calculations of pulmonary blood flow (Qp) with isolation of all sources of Qp, individualized measurements of resistance in isolated lung segments, and direct measurement of pulmonary venous pressure are typically used to assess PAH reversibility and the likelihood of surgical success. Acute administration of inhaled (nitric oxide) or intravenously administered (prostacyclin) pulmonary vascular agents is frequently used in such investigations to assess for acute reactivity and potential to subsequently (with surgical or pharmacological intervention) mimic achieved lowering of PVR and, when appropriate to anatomy and physiology, similar lowering of pulmonary artery pressures. However, studies have not been performed that firmly establish the pressures, flows, and resistances that define such reactivity. Many centers use a preoperative PVR less than 10 to 14 Wood units and a pulmonary/systemic resistance ratio less than or equal to two thirds as thresholds associated with better surgical outcomes (494,495), but individual institutions vary with regard to these thresholds, often modifying them according to the specific anatomic lesion and responses to acute vasodilator testing. All additional potential causes of PAH in this population must be excluded, because therapeutic strategies may differ significantly.
An important concept with regard to predicting the outcome of surgery, especially in borderline cases, is that PVR is flow dependent. Thus, it should not be assumed that PVR will necessarily fall in proportion to the reduction in shunt and pulmonary blood flow. High shunt flows can recruit pulmonary vasculature (thereby reducing PVR). With the elimination of shunt, these additionally recruited vascular beds may “de-recruit,” no longer accommodating the increased blood flow, and PVR (and hence pulmonary artery pressure) may fall less than would be predicted on the basis of the reduction of blood flow alone.
9.4.2. Eisenmenger Physiology
Diagnosis and evaluation of Eisenmenger physiology require a detailed history to look for all possible PAH triggers and a thorough understanding of current and past anatomy, as well as knowledge of all past surgical and medical interventions. Documentation of the size and direction of intracardiac or intravascular shunts present at the atrial, ventricular, or great arterial level is required, as is a precise documentation of the extent of the severity of pulmonary arteriolar hypertension. A suggested basic evaluation of adults with presumed Eisenmenger physiology includes assessment of anatomy, degree of PAH, ventricular function, and both the presence and magnitude of secondary complications. Evaluation includes finger and toe oximetry, chest x-ray, ECG, pulmonary function tests with volumes and CO2 diffusion, anatomic lesion definition (by use of noninvasive or invasive modalities, as necessary), pulmonary embolism–protocol CT with “chest windows,” complete blood count with indices, ferritin and iron studies, and renal and hepatic function tests, along with 6-minute walk testing (with or without oximetry or cardiopulmonary testing). Other tests may be performed as indicated if the diagnosis is less certain: hepatitis B and C panels; cryoglobulins; human immunodeficiency virus serologies; procoagulant evaluation; and rheumatologic serologies (including scleroderma, mixed connective tissue disorder, and systemic lupus erythematosus). A complete cardiac catheterization, with potential for vasodilator testing or anatomic interventions, should be performed, but only at a center with expertise in the diagnosis and management of ACHD and adult patients with PAH. Open lung biopsy presently has a very limited role in patient diagnosis or management.
9.5. Management Strategies
9.5.1. Recommendations for Medical Therapy of Eisenmenger Physiology
1. It is recommended that patients with Eisenmenger syndrome avoid the following activities or exposures, which carry increased risks:
a. Pregnancy. (Level of Evidence: B)
b. Dehydration. (Level of Evidence: C)
c. Moderate and severe strenuous exercise, particularly isometric exercise. (Level of Evidence: C)
d. Acute exposure to excessive heat (eg, hot tub or sauna). (Level of Evidence: C)
e. Chronic high-altitude exposure, because this causes further reduction in oxygen saturation and increased risk of altitude-related cardiopulmonary complications (particularly at an elevation greater than 5000 feet above sea level). (Level of Evidence: C)
f. Iron deficiency. (Level of Evidence: B)
2. Patients with Eisenmenger syndrome should seek prompt therapy for arrhythmias and infections. (Level of Evidence: C)
3. Patients with Eisenmenger syndrome should have hemoglobin, platelet count, iron stores, creatinine, and uric acid assessed at least yearly. (Level of Evidence: C)
4. Patients with Eisenmenger syndrome should have assessment of digital oximetry, both with and without supplemental oxygen therapy, at least yearly. The presence of oxygen-responsive hypoxemia should be investigated further. (Level of Evidence: C)
5. Exclusion of air bubbles in intravenous tubing is recommended as essential during treatment of adults with Eisenmenger syndrome. (Level of Evidence: C)
6. Patients with Eisenmenger syndrome should undergo noncardiac surgery and cardiac catheterization only in centers with expertise in the care of such patients. In emergent or urgent situations in which transportation is not feasible, consultation with designated caregivers in centers with expertise in the care of patients with Eisenmenger syndrome should be performed and sustained throughout care. (Level of Evidence: C)
1. All medications given to patients with Eisenmenger physiology should undergo rigorous review for the potential to change systemic blood pressure, loading conditions, intravascular shunting, and renal or hepatic flow or function. (Level of Evidence: C)
2. Pulmonary vasodilator therapy can be beneficial for patients with Eisenmenger physiology because of the potential for improved quality of life. (Level of Evidence: C)
An emphasis on patient education and avoidance of destabilizing situations and volume shifts that result in alteration of catecholamines, extreme fatigue, high-altitude exposure, contact with cigarette smoke, changes in renal or hepatic function, or use of medications that may modulate flow to or function of these organs is advocated. Avoidance of pregnancy and iron deficiency and prompt therapy for arrhythmia or infection are recommended. A concept of team planning for all procedures is mandated because of the potential for morbid and mortal outcomes of even the simplest of interventions for any ailment. The optimal type and mode of anesthetic administration should be individualized by experts in the care of persons with Eisenmenger physiology. Risk of right-to-left embolization warrants avoidance of bubbles, and consideration of the use of air filters on all venous catheters still tends to be advocated, although controversy exists regarding the relative benefit obtained compared with meticulous guarding of all intravenous administration systems.
Erythrocytosis tends to remain stable in cyanotic patients, and alterations in serum hemoglobin tend to be indicative of intercurrent issues that require their own correction (refer to Section 7.6.5, Cyanosis). Therapeutic phlebotomy or erythropheresis has a very limited role in patient management and should only be performed if the hemoglobin is more than 20 g per dL and the hematocrit is greater than 65% with associated symptoms of hyperviscosity and no evidence of dehydration. Iron deficiency anemia should be avoided, given the suggestion that iron-deficient red blood cells with less oxygen-carrying capacity and less potential for deformation may lead to increased incidence of strokes and vascular complication (184). Achievement of replete iron stores, combined with optimal serum hemoglobin and blood viscosity, is the optimal approach (496,497).
Therapies for adults with CHD-PAH have been limited and have included oxygen, warfarin, diuretics, calcium channel blockers, long-term continuous intravenous epoprostenol, oral prostacyclin analogues, oral endothelin antagonists, oral phosphodiesterase inhibition, and lung or lung/heart transplantation. The benefit of supplemental oxygen administration is a matter of debate given the conflict between recognized concomitant oxygen-responsive and -unresponsive components to hypoxemia in many patients and the lack of sufficient trial data to assess benefit (498,499). The use of oxygen therapy may help if there is a component of oxygen-responsive vasoconstriction. Despite few data, calcium channel blockers have shown limited results or have worsened well-being.
Transplantation has offered a limited survival benefit for this patient population, given the unpredictability of transplant-free survival and significantly higher perioperative mortality in this cohort of patients, although individual outcomes may warrant individual considerations (500). Newer theoretical procedures such as pulmonary artery banding have not been studied adequately. Symptomatic adults with Eisenmenger physiology should be counseled about the results of randomized, controlled trials of vasomodulator therapies for PAH, with particular emphasis on those trials performed specifically in adults with Eisenmenger physiology.
Anticoagulation with warfarin is widely used in patients with PAH on the basis of observational studies, in the absence of randomized, controlled trials supporting benefit or evaluating risk. In adults with Eisenmenger physiology, recognition of in vivo pulmonary thrombus (350), contrasted with reports of in vitro abnormalities of coagulation in persons with cyanosis (501), has led to debate over the potential benefit of oral anticoagulant therapy, particularly with the concomitant bleeding diathesis inherent in the condition. In patients with active or chronic hemoptysis, anticoagulation is contraindicated.
The theoretical possibility of worsening of right-to-left shunting raises questions about the safety of using pulmonary artery modulating therapies that also have systemic vasodilator potential. Nevertheless, some of these agents (intravenous prostacyclin and oral sildenafil) have yielded improvements in hemodynamics, exercise tolerance, and/or systemic arterial oxygen saturation in limited case studies (501–507). The potential for significant adverse reaction due to these agents has been recognized.
Randomized, controlled trials showing a benefit of many of these agents for patients with PAH have included small numbers of patients with Eisenmenger physiology; however, the utility of these trials in guiding therapy for patients with Eisenmenger physiology is limited, given that the trials were not designed to test hypotheses specifically in such patients and were not randomized to therapy within an Eisenmenger subgroup (505–509). Results of the first randomized, controlled trial of medical therapy in adults with Eisenmenger syndrome due to predominantly either ASD or VSD, with oral bosentan compared with placebo (BREATHE-5, the Bosentan Randomized trial of Endothelin Antagonist THErapy-5), documented therapeutic safety and improvement in symptomatic measures, 6-minute walk distance, and hemodynamics after short-term (4 months) use of bosentan (510). The use of these agents should be restricted to centers with demonstrated expertise in CHD-PAH.
9.6. Key Issues to Evaluate and Follow-Up
9.6.1. Recommendations for Reproduction
1. Women with severe CHD-PAH, especially those with Eisenmenger physiology, and their partners should be counseled about the absolute avoidance of pregnancy in view of the high risk of maternal death, and they should be educated regarding safe and appropriate methods of contraception. (Level of Evidence: B)
2. Women with CHD-PAH who become pregnant should:
a. Receive individualized counseling from cardiovascular and obstetric caregivers collaborating in care and with expertise in management of CHD-PAH. (Level of Evidence: C)
b. Undergo the earliest possible pregnancy termination after such counseling. (Level of Evidence: C)
3. Surgical sterilization carries some operative risk for women with CHD-PAH but is a safer option than pregnancy. In view of advances in minimally invasive techniques, the risks and benefits of sterilization modalities should be discussed with an obstetrician experienced in management of high-risk patients, as well as with a cardiac anesthesiologist. (Level of Evidence: C)
1. Pregnancy termination in the last 2 trimesters of pregnancy poses a high risk to the mother. It may be reasonable, however, after the risks of termination are balanced against the risks of continuation of the pregnancy. (Level of Evidence: C)
1. Pregnancy in women with CHD-PAH, especially those with Eisenmenger physiology, is not recommended and should be absolutely avoided in view of the high risk of maternal mortality. (Level of Evidence: B)
2. The use of single-barrier contraception alone in women with CHD-PAH is not recommended owing to the frequency of failure. (Level of Evidence: C)
3. Estrogen-containing contraceptives should be avoided. (Level of Evidence: C)
Pregnancy carries particular risk for individuals with CHD-PAH, especially those with Eisenmenger physiology, with mostly older case series suggesting maternal mortality in the latter group of up to 50% and similarly high levels of fetal loss. Even after a successful pregnancy, maternal mortality may be particularly increased in the first several days after delivery (511). Termination of pregnancy, particularly in its mid and later phases, with its concomitant volume and hormonal fluctuations also carries a high maternal risk. Termination in the first trimester is the safer option. Recent case series have reported individual ability of the adult with Eisenmenger physiology to survive pregnancy with concomitant use of modern vasomodulatory agents. It remains unclear whether the potential for pregnancy survival is any different in persons with Eisenmenger syndrome than in adults with PAH without intravascular shunting, and because of the lack of predictability of outcome, pregnancy remains absolutely contraindicated for these patients. Counseled contraception is strongly advised, although the particular method of such is a matter of debate. Maternal sterilization carries a defined operative risk of mortality, and endoscopic sterilization may be the safer option. Hormonal therapies increase the preexisting potential for thrombosis, although progesterone-only preparations may be considered. Barrier methods have an increased rate of failure, and intrauterine device implantation carries anecdotally increased infection risk, although the highest risk is for local infection in multipartner couples. There is no consensus on comparative contraceptive risks; therefore, the patient should discuss options with a high-risk obstetrician (maternal fetal medicine specialist).
9.6.3. Other Interventions
There are limited case data on surgical or transcatheter attempts to limit pulmonary blood flow so as to potentially remodel the pulmonary vascular bed and alter PVR (509).
9.6.4. Recommendations for Follow-Up
1. Patients with CHD-related PAH should:
a. Have coordinated care under the supervision of a trained CHD and PAH provider and be seen by such individuals at least yearly. (Level of Evidence: C)
b. Have yearly comprehensive evaluation of functional capacity and assessment of secondary complications. (Level of Evidence: C)
c. Discuss all medication changes or planned interventions with their CHD-related PAH caregiver. (Level of Evidence: C)
1. Endocardial pacing is not recommended in patients with CHD-PAH with persistent intravascular shunting, and alternative access for pacing leads should be sought (the risks should be individualized). (512) (Level of Evidence: B)
9.6.5. Endocarditis Prophylaxis
Refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information.
10. Tetralogy of Fallot
10.1 Definition and Associated Lesions
Tetralogy of Fallot has 4 components: subpulmonary infundibular stenosis, a VSD, an aorta that overrides the VSD by less than 50% of its diameter, and RV hypertrophy. There can be varying levels of severity, and a morphological spectrum exists. The most extreme form is pulmonary atresia with VSD, which is not discussed here. The single and large VSD is usually in the subaortic position. The pulmonary valve is often small and stenotic. Pulmonary artery anomalies are frequent and include hypoplasia and stenosis. Pulmonary artery hypoplasia may involve the pulmonary trunk or the branch pulmonary arteries. Pulmonary artery stenosis at any of these levels is common. Occasionally, the pulmonary artery is absent, most often on the left side. Associated anomalies can include a secundum ASD, AVSD (usually in a patient with Down syndrome), and a right aortic arch in approximately 25% of cases. Coronary artery anomalies also occur, most commonly with a left anterior descending coronary artery arising from the right coronary artery and crossing the RVOT (approximately 3% of cases).
10.2. Clinical Course (Unrepaired)
10.2.1. Presentation as an Unoperated Patient
Presentation as an unoperated patient is now rare in countries with access to modern cardiac surgery, but it can be seen in immigrants living in the United States and in patients who live in countries without access to surgical repair. An occasional patient is seen with relatively mild pulmonary obstruction and mild cyanosis (the so-called pink tetralogy), in which case the diagnosis may not be made until adult life. It is usually mistaken for a small VSD because of the loud precordial murmur. Other patients who have not had previous access to health care and who have severe RV outflow obstruction but abundant aorticopulmonary collaterals may present late with cyanosis and loud continuous murmurs over the thorax. TTE and cardiac catheterization may confirm the diagnosis. The course and anatomy of the epicardial coronary arteries should be defined before definitive repair.
10.2.2. Postsurgical Presentation
Almost all patients with repairable forms of tetralogy of Fallot in the United States will have had reparative surgery. They are usually asymptomatic. Exercise limitation or atrial and/or ventricular arrhythmias imply hemodynamic difficulties.
10.3. Clinical Features and Evaluation
10.3.1. Clinical Examination
The typical postrepair patient has a soft ejection systolic murmur from the RVOT. The presence of a low-pitched, delayed diastolic murmur in the pulmonary area is consistent with pulmonary regurgitation. Such patients usually have an absent P2 component of the second sound. The patient may have a pansystolic murmur of a VSD patch leak. A diastolic murmur of AR may also be heard. The occasional adult patient may present having had a palliative shunt only. Such patients usually have cyanosis and clubbing. If the shunt is patent, a continuous murmur may be heard. In the presence of a prior classic Blalock-Taussig shunt, the brachial and radial pulses may be diminished or absent on that side.
In patients with transventricular repairs (the norm until the 1990s), complete right bundle-branch block is almost always present, in which case QRS duration may reflect the degree of RV dilation. A QRS duration of 180 ms or more has been identified as a risk factor for sustained VT and sudden cardiac death (167). The presence of atrial flutter or fibrillation or of sustained VT reflects severe hemodynamic difficulties (513,514).
10.3.3. Chest X-Ray
In patients with a good hemodynamic result, the heart size is usually normal. Cardiomegaly usually reflects important pulmonary regurgitation and/or TR. The aortic arch is right-sided in 25% of cases.
10.3.4. Initial Surgical Repair
Complete repair is considered 1) in palliated patients without irreversible PAH or unfavorable pulmonary artery anatomy and 2) as a primary operation, usually performed in the first year of life. An adult who has undergone palliation earlier in life can be considered for surgery for complete repair after thorough evaluation indicates favorable anatomy and hemodynamics.
Complete repair consists of VSD closure and relief of RVOT obstruction. Relief of RVOT obstruction may include simple resection of infundibular stenosis (muscle), but if the pulmonary annulus is small, more extensive surgery may be necessary. This may include RV outflow patch augmentation or placement of a transannular patch that disrupts the integrity of the pulmonary valve. Occasionally, an extracardiac conduit must be placed from the right ventricle to the pulmonary artery when an anomalous coronary artery crosses the RVOT. If the pulmonary valve itself is abnormal, a pulmonary valvotomy or pulmonary valve resection may be necessary. Effort should be made to preserve the pulmonary valve during the primary operation when performed in infancy. A PFO or small ASD is usually closed. When complete repair is performed in adulthood, pulmonary valve replacement may be required if the native pulmonary valve integrity is disrupted (Table 14).
Key postoperative issues are summarized below:
• Residual pulmonary regurgitation
• RV dilation and dysfunction from pulmonary regurgitation, possibly with associated TR
• Residual RVOT obstruction
• Branch pulmonary artery stenosis or hypoplasia
• Sustained VT
• Sudden cardiac death
• AV block, atrial flutter, and/or atrial fibrillation
• Progressive AR
• Syndromal associations.
The most common problem encountered in the adult patient after repair is that of pulmonary regurgitation. This is frequently missed on clinical examination because the murmur is short and quiet and the pulmonary regurgitation is often overlooked on echocardiography. Patients who present with arrhythmias or cardiomegaly should undergo a thorough evaluation to rule out underlying hemodynamic abnormalities. AR may also occur, often accompanied by aortic root dilatation.
10.4. Recommendations for Evaluation and Follow-Up of the Repaired Patient
1. Patients with repaired tetralogy of Fallot should have at least annual follow-up with a cardiologist who has expertise in ACHD. (Level of Evidence: C)
2. Patients with tetralogy of Fallot should have echocardiographic examinations and/or MRIs performed by staff with expertise in ACHD. (Level of Evidence: C)
3. Screening for heritable causes of their condition (eg, 22q11 deletion) should be offered to all patients with tetralogy of Fallot. (Level of Evidence: C)
4. Before pregnancy or if a genetic syndrome is identified, consultation with a geneticist should be arranged for patients with tetralogy of Fallot. (Level of Evidence: B)
5. Patients with unrepaired or palliated forms of tetralogy should have a formal evaluation at an ACHD center regarding suitability for repair. (Level of Evidence: B)
All patients should have regular follow-up with a cardiologist who has expertise in ACHD (3,4,10,43,82,515,516). The frequency, although typically annual, may be determined by the extent and degree of residual abnormalities. Appropriate imaging (2-dimensional echocardiography annually in most cases and/or MRI every 2 to 3 years) should be undertaken by staff trained in imaging of complex congenital heart defects. An ECG should be performed annually to assess cardiac rhythm and to evaluate QRS duration. Periodic cardiopulmonary testing may be helpful to facilitate serial follow-up of exercise capacity and to evaluate the potential for exercise-induced arrhythmias. Other testing should be arranged in response to clinical problems, particularly a Holter monitor if there is concern about arrhythmias.
10.4.1. Recommendation for Imaging
1. Comprehensive echocardiographic imaging should be performed in a regional ACHD center to evaluate the anatomy and hemodynamics in patients with repaired tetralogy of Fallot. (Level of Evidence: B)
Echocardiography is usually very helpful in assessing a patient after repair of tetralogy. The presence and severity of residual RVOT obstruction and pulmonary regurgitation can usually be assessed along with the presence or absence of TR. The tricuspid regurgitant velocity facilitates measurement of the RV pressure. A residual VSD may be seen. RV volume and wall motion are not reliably quantified by standard techniques, although size and function can be determined qualitatively. Doppler measurement of the RV myocardial performance index may be a useful adjunct to serial assessment of RV systolic function. Atrial size can be assessed. Aortic root dilation and AR should be sought and evaluated at regular intervals.
MRI is now seen as the reference standard (517,518) for assessment of RV volume and systolic function. It can be helpful in assessing the severity of pulmonary regurgitation and in evaluating important associated pathology, especially involving the pulmonary arteries and the ascending aorta. Left-sided heart disease can also be evaluated. Recently, CT scanning has become available (519–521) to make similar measurements of RV volume and systolic function and is potentially helpful in patients who cannot have an MRI, although because of the higher radiation exposure, it is not suitable for serial measurements.
10.5. Recommendations for Diagnostic and Interventional Catheterization for Adults With Tetralogy of Fallot
1. Catheterization of adults with tetralogy of Fallot should be performed in regional centers with expertise in ACHD. (Level of Evidence: C)
2. Coronary artery delineation should be performed before any intervention for the RVOT. (Level of Evidence: C)
1. In adults with repaired tetralogy of Fallot, catheterization may be considered to better define potentially treatable causes of otherwise unexplained LV or RV dysfunction, fluid retention, chest pain, or cyanosis. In these circumstances, transcatheter interventions may include:
a. Elimination of residual shunts or aortopulmonary collateral vessels. (Level of Evidence: C)
b. Dilation (with or without stent implantation) of RVOT obstruction. (Level of Evidence: B)
c. Elimination of additional muscular or patch margin VSD. (Level of Evidence: C)
d. Elimination of residual ASD. (Level of Evidence: B)
For the unusual case of a patient with tetralogy of Fallot who has undergone palliation with a surgical shunt, catheterization should be performed to assess the potential for repair. The presence or absence of additional muscular VSDs may be determined, as well as the course and anatomy of the epicardial coronary arteries. The pulmonary architecture and vascular pressure and resistance should be delineated, because pulmonary artery distortion and PAH are frequent sequelae of palliative surgical shunts. Potential catheter interventions include elimination of collateral vessels or systemic–pulmonary artery shunts, dilation/stent implantation of obstructed pulmonary arteries, and, more recently, the possibility of percutaneous pulmonary valve implantation. Heart catheterization is not used routinely in the assessment of patients who have undergone repair, except when surgery or other therapy is being considered or for the evaluation of the pulmonary and coronary arteries.
10.5.1. Branch Pulmonary Artery Angioplasty
Balloon angioplasty of a branch pulmonary artery results in intimal and medial dissection and subsequent inflammatory repair and increase in vessel size. Dilation may be considered when RV pressure is more than 50% of the systemic level or at lower pressure when there is RV dysfunction. Balloon pulmonary artery angioplasty may also be considered when there is unbalanced pulmonary blood flow greater than 75%, 25%, or otherwise unexplained dyspnea with severe vascular stenosis (522,523). Pulmonary artery balloon angioplasty may be an effective way to reduce obstruction to pulmonary blood flow, thereby increasing pulmonary vascular capacitance and decreasing PVR (524). Balloon angioplasty is usually effective for intermediate-branch pulmonary artery stenoses/occlusions, although it may require coimplantation of large stents (up to 24 to 26 mm diameter in width, up to 5.8 cm in length) in more proximal main and early branch pulmonary arteries or right ventricle–to–pulmonary artery conduits. Intravascular stents are of potential benefit as well in the presence of intimal flaps, vessel kinks, and stenoses, especially in the early perioperative period. Postdeployment antiinflammatory or antiproliferative/anticoagulant strategies remain undefined. Stent redilation has been shown to be effective in selected patients as late as 10 years after implantation (525). The applicability of these techniques has recently been extended to adults with very distal segmental pulmonary artery stenoses and appears promising (427,526). The transcatheter approach to the management of residual muscular or patch margin VSDs (indications typically include a Qp/Qs greater than 1.5 to 2.0, or less in the setting of PAH, left atrial hypertension, or LV failure) remains an effective alternative to reoperative surgical closure (527,528).
10.5.2. Exercise Testing
Exercise testing may be used to assess functional capacity objectively and to evaluate possible exertional arrhythmias. Serial evaluations may be helpful (55,529).
10.5.3. Diagnostic Catheterization
Catheter assessments and interventions for adults with previously repaired tetralogy of Fallot are indicated for the following when adequate data cannot be obtained noninvasively:
• Assessment of hemodynamics
• Assessment of pulmonary blood flow and resistance
• Assessment of the nature of RV outflow or pulmonary artery obstruction
• Delineation of coronary artery origin and course before any interventional procedure
• Assessment of ventricular function and presence of residual septal defects, as well as assessment of the degree of mitral regurgitation or AR. The potential for placement of transcatheter implants to reduce or eliminate residual VSDs should be discussed in advance with the patient and medical-surgical team
• Assessment of the significance of flow across a PFO or ASD and its potential elimination
• Performance of coronary angiography, with potential to eliminate symptomatic obstructive lesions
• Assessment of pulmonary regurgitation and right-sided heart failure.
10.6. Problems and Pitfalls in the Patient With Prior Repair
The following problems occur in patients after repair of tetralogy of Fallot:
• Cardiomegaly on chest x-ray should prompt the search for a residual hemodynamic lesion (commonly pulmonary regurgitation).
• The development of arrhythmias (atrial or ventricular) should prompt the search for an underlying hemodynamic abnormality (commonly pulmonary regurgitation).
• Diagnostic confusion may occur in the context of double-outlet right ventricle, in which the aorta overrides the right ventricle by more than 50%. In such cases, the VSD patch is more extensive and predisposes to the presence of postoperative subaortic obstruction, which should be carefully excluded.
• Hypoxemia in postoperative patients should prompt a search for a PFO or ASD with a right-to-left shunt.
• The presence of RV enlargement or dysfunction and the presence of important TR should prompt the search for a residual hemodynamic lesion (commonly pulmonary regurgitation).
Some postoperative patients may have LV dysfunction. This may relate to prolonged cardiopulmonary bypass, poor myocardial protection from an early surgical era, or trauma to a coronary artery at the time of repair, or it may be secondary to severe RV dysfunction.
10.7. Management Strategy for the Patient With Prior Repair
10.7.1. Medical Therapy
Most patients need no regular medication in the absence of significant residual hemodynamic abnormality. Heart failure medications may be necessary in the setting of RV and LV dysfunction.
10.8. Recommendations for Surgery for Adults With Previous Repair of Tetralogy of Fallot
1. Surgeons with training and expertise in CHD should perform operations in adults with previous repair of tetralogy of Fallot. (Level of Evidence: C)
2. Pulmonary valve replacement is indicated for severe pulmonary regurgitation and symptoms or decreased exercise tolerance. (Level of Evidence: B)
3. Coronary artery anatomy, specifically the possibility of an anomalous anterior descending coronary artery across the RVOT, should be ascertained before operative intervention. (Level of Evidence: C)
1. Pulmonary valve replacement is reasonable in adults with previous tetralogy of Fallot, severe pulmonary regurgitation, and any of the following:
a. Moderate to severe RV dysfunction. (Level of Evidence: B)
b. Moderate to severe RV enlargement. (Level of Evidence: B)
c. Development of symptomatic or sustained atrial and/or ventricular arrhythmias. (Level of Evidence: C)
d. Moderate to severe TR. (Level of Evidence: C)
2. Collaboration between ACHD surgeons and ACHD interventional cardiologists, which may include preoperative stenting, intraoperative stenting, or intraoperative patch angioplasty, is reasonable to determine the most feasible treatment for pulmonary artery stenosis. (Level of Evidence: C)
3. Surgery is reasonable in adults with prior repair of tetralogy of Fallot and residual RVOT obstruction (valvular or subvalvular) and any of the following indications:
a. Residual RVOT obstruction (valvular or subvalvular) with peak instantaneous echocardiography gradient greater than 50 mm Hg. (Level of Evidence: C)
b. Residual RVOT obstruction (valvular or subvalvular) with RV/LV pressure ratio greater than 0.7. (Level of Evidence: C)
c. Residual RVOT obstruction (valvular or subvalvular) with progressive and/or severe dilatation of the right ventricle with dysfunction. (Level of Evidence: C)
d. Residual VSD with a left-to-right shunt greater than 1.5:1. (Level of Evidence: B)
e. Severe AR with associated symptoms or more than mild LV dysfunction. (Level of Evidence: C)
f. A combination of multiple residual lesions (eg, VSD and RVOT obstruction) leading to RV enlargement or reduced RV function. (Level of Evidence: C)
Late survival after tetralogy repair is excellent; 35-year survival is approximately 85%. The need for reintervention, usually for pulmonary valve insertion, increases after the second decade of life. Surgical intervention is indicated for symptomatic patients with severe pulmonary regurgitation or asymptomatic patients with severe PS or pulmonary regurgitation in association with signs of progressive or severe RV enlargement or dysfunction. Patients with RV–to–pulmonary artery conduit repairs often require further intervention for conduit stenosis or regurgitation. Any intervention that involves the RVOT requires careful preoperative assessment of the coronary anatomy to avoid interruption of an important coronary vessel. Some patients experience increasing AR, which requires surgical intervention.
10.8.1. Recommendations for Interventional Catheterization
1. Interventional catheterization in an ACHD center is indicated for patients with previously repaired tetralogy of Fallot with the following indications:
a. To eliminate residual native or palliative systemic–pulmonary artery shunts. (Level of Evidence: B)
b. To manage coronary artery disease. (Level of Evidence: B)
1. Interventional catheterization in an ACHD center is reasonable in patients with repaired tetralogy of Fallot to eliminate a residual ASD or VSD with a left-to-right shunt greater than 1.5:1 if it is in an appropriate anatomic location. (Level of Evidence: C)
Interventional catheterization in previously repaired tetralogy of Fallot should be planned carefully with the medical and surgical team in an ACHD center. Although there is experience in the use of catheter devices to close residual shunts, experience with the use of percutaneous stent-valve implants in the RV outflow for patients with pulmonary regurgitation and right-sided heart failure is recent, and efficacy/safety remains undefined, but this technique appears promising.
10.9. Key Issues to Evaluate and Follow-Up
10.9.1. Recommendations for Arrhythmias: Pacemaker/Electrophysiology Testing
1. Annual surveillance with history, ECG, assessment of RV function, and periodic exercise testing is recommended for patients with pacemakers/automatic implantable cardioverter defibrillators. (Level of Evidence: C)
1. Periodic Holter monitoring can be beneficial as part of routine follow-up. The frequency should be individualized depending on the hemodynamics and clinical suspicion of arrhythmia. (Level of Evidence: C)
1. Electrophysiology testing in an ACHD center may be reasonable to define suspected arrhythmias in adults with tetralogy of Fallot. (Level of Evidence: C)
Despite overall excellent hemodynamic outcomes after surgery for tetralogy of Fallot, there remains a concerning incidence of unexpected sudden death during long-term follow-up (Table 15). VT appears to be the mechanism responsible for most of these events, although rapidly conducted IART (atrial flutter) or AV block may be responsible in some cases. The incidence of sudden death for the adult tetralogy population can be estimated from several large series to be on the order of 2.5% per decade of follow-up (162,166,346,530,531). Although this incidence is lower than the risk of sudden cardiac death in other forms of adult heart disease (eg, ischemic myopathy or hypertrophic myopathy), it is nonetheless a devastating outcome that has been the topic of intense clinical investigation for more than 30 years (Table 16).
Numerous studies have attempted to define the mechanism and risk factors for the development of sudden arrhythmic death in this group. To date, no perfect risk-stratification scheme has emerged, although several isolated variables have been identified that correlate modestly well with malignant arrhythmias. As shown in Table 16, the earliest of these is related to compromised AV conduction, with the hypothesis that trauma to AV conduction tissues at the time of surgery (enough to cause permanent bifascicular block) could lead to late sudden death, presumably due to abrupt worsening of conduction with asystole (532). By the 1980s, however, the emphasis shifted away from AV block toward VT as the more common mechanism for sudden death in tetralogy patients (533–537). Multiple clinical and laboratory variables have since been linked to an elevated likelihood of VT, although the predictive accuracy for all these items remains imperfect. The general picture that emerges for the high-risk tetralogy patient involves some combination of 1) long-standing palliative shunts, 2) older age at the time of definitive surgery, 3) abnormal RV hemodynamics (due to pulmonary regurgitation and/or residual outflow obstruction), 4) high-grade ectopy on Holter monitor, and 5) inducible VT at electrophysiological study.(140,165,167,169,170,223,538–549) In addition, it has recently become apparent that reasonable correlation exists between VT and certain ECG findings, particularly QRS duration greater than 180 ms (167,170). This is not surprising considering that the most dramatic degrees of QRS prolongation tend to be seen among tetralogy patients with highly dysfunctional and dilated right ventricles (so-called mechanoelectric interaction). The QRS width on ECG can thus be viewed as a crude proxy for size and function of the right ventricle and can be tracked easily in any adult tetralogy patient who is not pacemaker dependent.
The proper risk-stratification approach to an asymptomatic adult with repaired tetralogy is a matter of debate. Most clinicians rely on a yearly evaluation with careful history, physical examination, and ECG, supplemented every few years with Holter monitoring or exercise testing to screen for high-grade ventricular ectopy, as well as periodic echocardiograms or MRIs to monitor the functional status of the right ventricle. Should nonsustained VT be detected on surveillance monitoring in an asymptomatic patient, or should RV function appear to be deteriorating, opinions still vary widely as to the appropriate response. Some would recommend electrophysiology study to refine the arrhythmia risk; some would advise surgery for pulmonary valve replacement if regurgitation exists; some would prescribe antiarrhythmic drugs; some would implant a primary prevention defibrillator; and some refrain from treatment as long as the patient remains free of symptoms. In the absence of firm outcome data, no single approach can be dismissed or advocated, so that therapy continues to be individualized for asymptomatic patients depending largely on institutional experience and philosophy.
Worrisome symptoms (ie, palpitations, dizziness, or an episode of syncope) should obviously heighten the index of suspicion for serious arrhythmias in tetralogy patients and trigger a prompt evaluation, including hemodynamic catheterization and electrophysiology study. At most centers, treatment is usually tailored according to data obtained from these invasive studies (169). Programmed ventricular stimulation during electrophysiology study provides reasonably good predictive information regarding the risk of future clinical VT events and all-cause mortality. In addition, if stable monomorphic VT can be induced and sustained sufficiently long to permit mapping, catheter ablation of the VT circuit might be considered. An electrophysiology study could also uncover IART (atrial flutter) as a contributing or confounding factor for a patient's symptoms, which might be addressed with catheter ablation at the same setting. Repairable hemodynamic issues may also be identified by echocardiography or cardiac catheterization that could possibly shift therapy toward a surgical approach, such as closure of a residual septal defect or relief of valve regurgitation, combined with intraoperative VT mapping and ablation.
Serious symptoms in adult patients with tetralogy of Fallot (ie, documented sustained VT or cardiac arrest) are now managed with implantable cardioverter defibrillators at almost all centers. There is little debate on this recommendation in the modern era of reliable transvenous devices (175). Even when catheter or surgical VT ablation has been tried with acute success, the recurrence risk for ablative therapy remains too uncertain (174) not to defer to an implantable cardioverter defibrillator in a patient who has clearly demonstrated the potential for life-threatening arrhythmias.
Pregnancy is not advised in patients with unrepaired tetralogy of Fallot. After repair of tetralogy of Fallot, the prognosis for a successful pregnancy is good provided there are no important hemodynamic residua and functional capacity is good. A comprehensive, informed cardiovascular evaluation is recommended before each pregnancy. Pregnancy is usually well tolerated even in the setting of severe pulmonary regurgitation, as long as RV function is no more than mildly depressed and sinus rhythm is maintained (550).
Patients with tetralogy of Fallot have an increased risk of fetal loss, and their offspring are more likely to have congenital anomalies than offspring in the general population, especially in the setting of a 22q11.2 microdeletion. Screening for 22q11.2 microdeletion should be considered in patients with conotruncal abnormalities before pregnancy to provide appropriate genetic counseling (69). In the absence of a 22q11 deletion, the risk of a fetus having CHD is approximately 4% to 6%. Fetal echocardiography should be offered to the mother in the second trimester.
Recommendations are summarized by Task Force 1 of the 36th Bethesda Conference on CHD (3).
10.9.4. Endocarditis Prophylaxis
Refer to the AHA guidelines on endocarditis prophylaxis (72). Also, refer to Section 1.6, Recommendations for Infective Endocarditis, for additional information.
11. Dextro-Transposition of the Great Arteries
TGA implies that each great artery arises from the wrong ventricle. TGA is AV concordance with ventriculoarterial discordance. As such, d-TGA implies that the aorta arises rightward and anterior to the pulmonary artery and arises from the systemic right ventricle.
11.2. Associated Lesions
Patients with d-TGA by definition have abnormal origins of the aorta and pulmonary artery. Anomalies of the coronary ostia are also common, and clear delineation is required. Additional congenital cardiac lesions include VSD, which occurs in up to 45% of cases, LVOT obstruction in approximately 25% of cases, and coarctation of the aorta in approximately 5%.
11.3. Clinical Course: Unrepaired
The infant with d-TGA will generally present with cyanosis, and some form of admixture of blood is required for survival. For the past 2 decades, ASO in the neonatal period has been the primary surgical repair of choice for uncomplicated d-TGA. In patients who present late (after 6 to 8 weeks of age), pulmonary artery banding to prepare the left ventricle is often necessary. Patients with d-TGA and associated VSD may undergo initial pulmonary artery banding or shunt procedure, depending on the presence or absence of subpulmonary artery obstruction. If there is an associated large VSD, a Rastelli procedure can be performed as a primary procedure. Initial presentation in adulthood would be rare unless the patient is from an underserved country and has the appropriate admixture of blood; usually, some form of VSD and pulmonic stenosis (tetralogy of Fallot physiology) or VSD with pulmonary vascular disease will be present with associated cyanosis.
11.4. Recommendation for Evaluation of the Operated Patient With Dextro-Transposition of the Great Arteries
1. Patients with repaired d-TGA should have annual follow-up with a cardiologist who has expertise in the management of ACHD patients. (Level of Evidence: C)
Most adults born with d-TGA will have had 1 or more operations in childhood. All patients should have regular follow-up with a cardiologist who has expertise in ACHD. The frequency may be determined by the degree of residual hemodynamic abnormalities, and these become more common, along with the occurrence of arrhythmias, with advancing age.
All operated d-TGA patients should be seen at least annually by a specialist in an ACHD regional center, with attention given to rhythm disorders, as well as ventricular and valvular function. Stress testing, including cardiopulmonary stress testing, should be applied selectively. If specialized testing is performed, it is best done at a regional center. If significant abnormalities are uncovered by these examinations, or if the patient is symptomatic, more frequent follow-up visits are indicated.
11.4.1. Clinical Features and Evaluation of Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure
Because the ASO only gained acceptance in the 1980s, many adults with d-TGA will have had a Mustard or Senning procedure. These procedures involve an atrial baffle that redirects the systemic venous blood to the mitral valve and left ventricle, which remains committed to the pulmonary artery. The pulmonary venous blood is redirected to the tricuspid valve and right ventricle, which remains committed to the aorta.
The atrial baffle (Mustard or Senning) procedure for d-TGA has characteristic late long-term problems. The most common early structural complications include baffle obstruction, which most commonly affects the superior limb rather than the inferior vena cava. Facial suffusion and “superior vena cava syndrome” may result. Inferior vena cava obstruction may cause hepatic congestion or even cirrhosis. Baffle leaks occur in up to 25% of patients. Most are small but may pose a risk of paradoxical embolus, particularly in the setting of atrial arrhythmias and an endocardial pacemaker. Pulmonary venous obstruction may also occur but is less common. Subpulmonary stenosis and PS may occur, in part related to the abnormal geometry of the left ventricle, which becomes distorted and compressed by the enlarged systemic right ventricle. Long term, the most important complication after atrial baffle is failure of the systemic right ventricle and systemic TR. These complications have a major impact on morbidity and mortality. Important but less common complications include PAH, residual VSD, dynamic subpulmonic stenosis, and a host of conduction and arrhythmia disturbances with the potential for implantation of permanent pacemakers or sudden death (37,108,111,551–558).
11.4.2. Clinical Examination
The adult with a prior atrial baffle procedure may have a relatively normal examination. More commonly, features of RV enlargement and TR are present. A loud A2 is usually present owing to the anterior position of the aorta and should not be confused with the loud P2 of PAH. A harsh systolic murmur may be a feature of a residual VSD or subpulmonary stenosis. Heart failure with features of systemic TR occurs with increasing frequency with longer duration of follow-up. Sudden cardiac death also occurs in a small percentage of patients.
The ECG demonstrates right-axis deviation and RV hypertrophy in patients with prior atrial baffle because the right ventricle is the SV. Bradycardia may represent a slow junctional rhythm or complete heart block. Rhythm abnormalities may be further elucidated by ambulatory rhythm monitoring (Holter or event recorder). Bradycardia and/or syncope may be presenting features related to sinus node dysfunction. Exercise testing to determine functional capacity and the potential for arrhythmias may be helpful.
11.4.4. Imaging for Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure
A narrow mediastinal shadow is common on chest x-ray in patients with d-TGA because of the parallel relationship of the great arteries. Ventricular size and pulmonary markings depend on patient status but are normal in patients with preserved ventricular function.
184.108.40.206. Recommendations for Imaging for Dextro-Transposition of the Great Arteries After Atrial Baffle Procedure
1. In patients with d-TGA repaired by atrial baffle procedure, comprehensive echocardiographic imaging should be performed in a regional ACHD center to evaluate the anatomy and hemodynamics. (Level of Evidence: B)
2. Additional imaging with TEE, CT, or MRI, as appropriate, should be performed in a regional ACHD center to evaluate the great arteries and veins, as well as ventricular function, in patients with prior atrial baffle repair of d-TGA. (Level of Evidence: B)
1. Echocardiography contrast injection with agitated saline can be useful to evaluate baffle anatomy and shunting in patients with previously repaired d-TGA after atrial baffle. (Level of Evidence: B)
2. TEE can be effective for more detailed baffle evaluation for patients with d-TGA. (Level of Evidence: B)
Comprehensive echocardiography is the mainstay of anatomic and hemodynamic assessment in most d-TGA patients after atrial baffle (108,111,551) and should be performed in an experienced center. Evaluation for intra-atrial baffle anatomy and shunting or obstruction may warrant echocardiography contrast injection. Assessment of systemic RV function is challenging by echocardiography. In addition to routine evaluation of ventricular size and function, measurement of the dP/dt of the AV regurgitant jet, Doppler tissue indices of annular motion, and the myocardial performance index may provide further insight (108,111,194,551,559,560). Tissue Doppler evaluation of myocardial acceleration during isovolumic contraction has been validated as a sensitive, noninvasive method to assess RV contractility (561,562). The myocardial performance index has the advantage of representing indices of both systolic and diastolic function without geometric constraints and has shown a relationship to BNP levels in ACHD patients (193). The coronary anatomy may be difficult to evaluate by echocardiography in the adult patient.
TEE is used to provide complementary information, including imaging of atrial anatomy, the presence of baffle leak or obstruction, and intracardiac thrombus. Radiological imaging with MRI or CT can be used to further assess atrial baffle patency, systemic ventricular function, and coronary anatomy.
MRI or magnetic resonance angiography is usually superior for evaluation of the extracardiac great arteries and veins. Comparison of TTE with cardiac MRI to assess ventricular function in adults after atrial baffle procedures has shown a good correlation between ventricular dimensions and function (563). MRI has also been shown to correlate closely with equilibrium radionuclide ventriculography assessment of RV ejection fraction (564). Current MRI techniques with first-pass, contrast-enhanced myocardial perfusion and myocardial delayed enhancement for viability, ischemia, and/or infarction are valuable tools (204).
11.4.5. Cardiac Catheterization
Cardiac catheterization is used to assess hemodynamics, baffle leak, superior vena cava or inferior vena cava pathway obstruction, pulmonary venous pathway obstruction, myocardial ischemia, unexplained systemic RV dysfunction, or significant LV stenosis (subpulmonary stenosis or LVOT obstruction) or to assess the PAH, with potential for vasodilator testing. Cardiac catheterization in patients after the atrial baffle procedure also provides the opportunity for intervention. For adults after palliative atrial baffle repair for d-TGA, VSD, and pulmonary vascular disease, catheterization may be indicated to assess the potential for pulmonary artery vasomodulator therapy.
11.5. Clinical Features and Evaluation of Dextro-Transposition of the Great Arteries After Arterial Switch Operation
The quality of life and health status of children 11 to 15 years of age after ASO are similar to those of normal children and significantly better than those of children who have undergone the atrial baffle procedure (565). In the current era, the preference is for an ASO, and the earliest survivors of this procedure are now adolescents and young adults (566,567). Long-term concerns after the ASO include coronary insufficiency, myocardial ischemia, ventricular dysfunction and arrhythmias, and issues regarding stenosis at the great arterial anastomotic sites, as well as development of aortic or pulmonary regurgitation. Significant neoaortic root dilatation and neoaortic valve regurgitation may develop over time, in part related to older age at the time of ASO or to an associated VSD with previous pulmonary artery banding (568).
11.5.1. Clinical Examination
Patients with prior ASO are now being seen in adult clinics. They may present with no specific findings on physical examination or with a systolic murmur related to arterial obstruction at the arterial anastomosis site. Diastolic murmurs of aortic or pulmonary regurgitation may be noted.
The ECG should be normal in patients after ASO without residua. Ischemic ECG changes are occasionally noted at rest or may occur with exercise, which suggests compromise of the coronary ostia. This should be evaluated further. RV and LV hypertrophy may occur with outflow obstruction.
11.5.3. Chest X-Ray
The chest x-ray after uncomplicated ASO should be unremarkable. A narrow pedicle may be noted.
11.5.4. Recommendations for Imaging for Dextro-Transposition of the Great Arteries After Arterial Switch Operation
1. Comprehensive echocardiographic imaging to evaluate the anatomy and hemodynamics in patients with d-TGA and prior ASO repair should be performed at least every 2 years at a center with expertise in ACHD. (Level of Evidence: C)
2. After prior ASO repair for d-TGA, all adults should have at least 1 evaluation of coronary artery patency. Coronary angiography should be performed if this cannot be established noninvasively. (Level of Evidence: C)
1. Periodic MRI or CT can be considered appropriate to evaluate the anatomy and hemodynamics in more detail. (Level of Evidence: C)
Echocardiography after ASO may demonstrate minimal findings or 1 or more of the recognized complications after ASO, which include the following: 1) stenosis at the arterial anastomotic sites, most commonly PS (567); 2) aortic root dilatation; and 3) neoaortic valve regurgitation (native pulmonary valve) (569). Coronary complications cannot be assessed adequately by echocardiography, but stress echocardiography may facilitate detection of ischemia. CT angiography has been used recently. Patients with intramural or single coronary arteries have increased mortality compared with those with the typical coronary pattern (570).
11.5.5. Recommendation for Cardiac Catheterization After Arterial Switch Operation
1. Coronary angiography is reasonable in all adults with d-TGA after ASO to rule out significant coronary artery obstruction. (Level of Evidence: C)
Coronary ischemia is a recognized late complication after ASO, with concern about ischemia or infarction reported in up to 8% of patients after ASO. These complications are due to reimplantation of the coronary arteries during surgery (567). Noninvasive testing for coronary ischemia may not be sufficiently sensitive, and coronary arteriography has been recommended 5, 10, and 15 years after ASO to detect significant late coronary artery stenosis. Aortic root angiography is recommended to detect ostial coronary artery disease.
Hemodynamic cardiac catheterization is used to assess pulmonary and aortic anastomosis obstruction when incompletely evaluated by other imaging modalities. Cardiac catheterization in patients after ASO also provides the opportunity for intervention.
11.6. Clinical Features and Evaluation: Dextro-Transposition of the Great Arteries After Rastelli Operation
The Rastelli operation for a combination of d-TGA, PS, and VSD has recognized complications that include RVOT or pulmonary conduit obstruction, superimposed RV failure, and TR. LVOT obstruction may also occur from the intraventricular baffle, arrhythmias from atriotomy and/or ventriculotomy incisions, residual VSD, myocardial hypertrophy, chamber enlargement, aortic root dilatation, and aortic valve regurgitation. The 3 most common late causes of postoperative death are sudden cardiac death, heart failure, and reoperation.
Patients who have undergone the Rastelli procedure may present with dyspnea, fatigue, or arrhythmias. As the pulmonary valve degenerates and becomes more obstructive, the A wave in the jugular venous pressure rises, an RV heave becomes apparent, and the murmur across the pulmonary valve becomes louder. The P2 becomes quieter, and when the valve is severely calcified, it disappears entirely.
The ECG in post-Rastelli patients often demonstrates right bundle-branch block. RV hypertrophy and progressive conduction disease may occur with time.
11.6.2. Chest X-Ray
The chest x-ray demonstrates a narrow pedicle with associated features of conduit replacement. Cardiac enlargement may occur with progressive valve disease.
Echocardiography is the primary imaging modality in patients with prior Rastelli operation. Recurrent RV or LV outflow obstruction can usually be delineated adequately by echocardiography-Doppler examination. Assessment of RV pressure and the occurrence of conduit obstruction can be facilitated by measurement of TR velocity. Additional important features should include assessment of pulmonary regurgitation, residual or baffle-margin VSD, and development of PAH.
11.7. Recommendations for Diagnostic Catheterization for Adults With Repaired Dextro-Transposition of the Great Arteries
1. Diagnostic catheterization of the adult with d-TGA should be performed in centers with expertise in the catheterization and management of ACHD patients. (Level of Evidence: C)
1. For adults with d-TGA after atrial baffle procedure (Mustard or Senning), diagnostic catheterization can be beneficial to assist in the following:
a. Hemodynamic assessment. (Level of Evidence: C)
b. Assessment of baffle leak. (Level of Evidence: B)
c. Assessment of superior vena cava or inferior vena cava pathway obstruction. (Level of Evidence: B)
d. Assessment of pulmonary venous pathway obstruction. (Level of Evidence: B)
e. Suspected myocardial ischemia or unexplained systemic RV dysfunction. (Level of Evidence: B)
f. Significant LV outflow obstruction at any level (LV pressure greater than 50% of systemic levels, or less in the setting of RV dysfunction). (Level of Evidence: B)
g. Assessment of PAH, with potential for vasodilator testing. (Level of Evidence: C)
2. For adults with d-TGA, VSD, and PS, after Rastelli-type repair, diagnostic catheterization can be beneficial to assist in the following:
a. Coronary artery delineation before any intervention for RVOT obstruction. (Level of Evidence: C)
b. Assessment of residual VSD. (Level of Evidence: C)
c. Assessment of PAH, with potential for vasodilator testing. (Level of Evidence: C)
d. Assessment of subaortic obstruction across the left ventricle–to–aorta tunnel. (Level of Evidence: C)
11.7.1. Problems and Pitfalls
The following are potential problems and pitfalls related to adults with d-TGA:
• Antiarrhythmic therapy, which might aggravate sinus node dysfunction in patients after atrial baffle operation, must be used cautiously.
• A detailed assessment of the atrial baffle for leak and obstruction must be undertaken before endocardial pacemaker implantation.
• There is potential for endocardial pacing leads to exacerbate obstruction in the atrial baffle.
• The absence of typical symptoms of coronary ischemia does not preclude the presence of important ostial coronary artery disease in patients with prior ASO.
11.8. Management Strategies
11.8.1. Medical Therapy
The role of medical treatment (eg, ACE inhibitors and beta blockers) to prevent or treat ventricular dysfunction has only been studied in small numbers, and its benefit is controversial (571–573). The role of ACE inhibitors and beta blockers remains uncertain, and beta blockers may precipitate complete AV block in patients with preexisting sinus node dysfunction. Therapy for heart failure now incorporates medications directed at the renin-angiotensin-aldosterone system.