The association between vegetation size and surgical treatment on 6-month mortality in left-sided infective endocarditis. Eur Heart J. 2019;40:2243 51. 68. Suzuki M, Takanashi S, Ohshima Y, et al. Critical potential of early cardiac surgery for infective endocarditis with cardio-embolic strokes. Int J Car- diol. 2017;227:222 4. 69. Garc a-Borbolla Fern ndez R, Sancho Jald n M, Calle P rez G, et al. Per- cutaneous treatment of mitral valve periprosthetic leakage. An alternative to high-risk surgery? Rev Esp Cardiol. 2009;62:438 41. 70. Nietlispach F, Johnson M, Moss RR, et al. Transcatheter closure of paraval- vular defects using a purpose-specific occluder. JACC Cardiovasc Interv. 2010;3:759 65. 71. Klug D, Lacroix D, Savoye C, et al. Systemic infection related to endocar- ditis on pacemaker leads: clinical presentation and management. Circula- tion. 1997;95:2098 107. 72. Baddour LM, Cha Y-M, Wilson WR. Clinical practice. Infections of cardio- vascular implantable electronic devices. N Engl J Med. 2012;367:842 9. 73. Cabell CH, Jollis JG, Peterson GE, et al. Changing patient character- istics and the effect on mortality in endocarditis. Arch Intern Med. 2002;162:90 4. 74. Ghoreishi M, Foster N, Pasrija C, et al. Early operation in patients with mitral valve infective endocarditis and acute stroke is safe. Ann Thorac Surg. 2018;105:69 75. 13. PREGNANCY AND VHD 13.1. Initial Management of Women With VHD Before and During Pregnancy 1. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC guidelines for the management of cardiovascular diseases during preg- nancy. Eur Heart J. 2018;39:3165 241. 2. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation. 2001;104:515 21. 3. Elkayam U, Bitar F. Valvular heart disease and pregnancy part I: native valves. J Am Coll Cardiol. 2005;46:223 30. 4. Le niak-Sobelga A, Tracz W, KostKiewicz M, et al. Clinical and echocardio- graphic assessment of pregnant women with valvular heart diseases ma- ternal and fetal outcome. Int J Cardiol. 2004;94:15 23. 5. Ducas RA, Javier DA, D Souza R, et al. Pregnancy outcomes in women with significant valve disease: a systematic review and meta-analysis. Heart. 2020;106:512 9. 6. Orwat S, Diller G-P, van Hagen IM, et al. Risk of pregnancy in moderate and severe aortic stenosis: from the multinational ROPAC registry. J Am Coll Cardiol. 2016;68:1727 37. 7. Roos-Hesselink J, Baris L, Johnson M, et al. Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy And Cardiac disease (ROPAC). Eur Heart J. 2019;40:3848 55. 8. Sliwa K, van Hagen IM, Budts W, et al. Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac CLINICAL STATEMENTS AND GUIDELINES Disease (ROPAC) of the European Society of Cardiology. Eur J Heart Fail. 2016;18:1119 28. 9. Silversides CK, Grewal J, Mason J, et al. Pregnancy outcomes in women with heart disease: the CARPREG II study. J Am Coll Cardiol. 2018;71:2419 30. 10. Thomas E, Yang J, Xu J, et al. Pulmonary hypertension and pregnancy outcomes: insights from the national inpatient sample. J Am Heart Assoc. 2017;6:e006144. 11. Sugishita Y, Ito I, Kubo T. Pregnancy in cardiac patients: possible influence of volume overload by pregnancy on pulmonary circulation. Jpn Circ J. 1986;50:376 83. 12. van Hagen IM, Thorne SA, Taha N, et al. Pregnancy outcomes in women with rheumatic mitral valve disease: results from the Registry of Pregnancy and Cardiac Disease. Circulation. 2018;137:806 16. 13. Lancellotti P, Lebois F, Simon M, et al. Prognostic importance of quantita- tive exercise Doppler echocardiography in asymptomatic valvular aortic stenosis. Circulation. 2005;112:I377 82. 14. Mar chaux S, Hachicha Z, Bellouin A, et al. Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis. Eur Heart J. 2010;31:1390 7. 15. Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J. 2005;26:1309 13. 13.1.1. Medical Therapy for Women With VHD Before and During Pregnancy 1. Elkayam U, Bitar F. Valvular heart disease and pregnancy part I: native valves. J Am Coll Cardiol. 2005;46:223 30. 2. al Kasab SM, Sabag T, al Zaibag M, et al. Beta-adrenergic receptor block- ade in the management of pregnant women with mitral stenosis. Am J Obstet Gynecol. 1990;163:37 40. 3. Nakhjavan FK, Katz MR, Maranhao V, et al. Analysis of influence of cat- echolamine and tachycardia during supine exercise in patients with mitral stenosis and sinus rhythm. Br Heart J. 1969;31:753 61. 4. Bhatia ML, Shrivastava S, Roy SB. Immediate haemodynamic effects of a beta adrenergic blocking agent-propranolol-in mitral stenosis at fixed heart rates. Br Heart J. 1972;34:638 44. 5. Lydakis C, Lip GY, Beevers M, et al. Atenolol and fetal growth in pregnan- cies complicated by hypertension. Am J Hypertens. 1999;12:541 7. 6. Ruys TP, Maggioni A, Johnson MR, et al. Cardiac medication during preg- nancy, data from the ROPAC. Int J Cardiol. 2014;177:124 8. 7. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC guidelines for the management of cardiovascular diseases during preg- nancy. Eur Heart J. 2018;39:3165 241. 8. Taylor J. The first ESC guidelines on the management of cardiovascular diseases during pregnancy. Eur Heart J. 2011;32:3055 6. 9. Schaefer C. Angiotensin II-receptor-antagonists: further evidence of feto- toxicity but not teratogenicity. Birth Defects Res Part A Clin Mol Teratol. 2003;67:591 4. 10. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital mal- formations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354:2443 51. 11. Shotan A, Widerhorn J, Hurst A, et al. Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evi- dence, potential mechanisms, and recommendations for use. Am J Med. 1994;96:451 6. 12. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071 104. 13. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused up- date of the 2014 AHA/ACC/HRS guideline for the management of pa- tients with atrial fibrillation: a report of the American College of Cardiol- ogy/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Developed in collaboration with the Society of Thoracic Surgeons. Circulation. 2019;140:e125 51. 13.1.2. Intervention for Women With Native VHD Before and During Pregnancy 13.1.2.1. Pre-Pregnancy Intervention 1. Le niak-Sobelga A, Tracz W, KostKiewicz M, et al. Clinical and echocar- diographic assessment of pregnant women with valvular heart diseases maternal and fetal outcome. Int J Cardiol. 2004;94:15 23. 2. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation. 2001;104:515 21. 3. Hameed A, Karaalp IS, Tummala PP, et al. The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol. 2001;37:893 9. 4. Barbosa PJ, Lopes AA, Feitosa GS, et al. Prognostic factors of rheumatic mitral stenosis during pregnancy and puerperium. Arq Bras Cardiol. 2000;75:215 24. 5. Bhatla N, Lal S, Behera G, et al. Cardiac disease in pregnancy. Int J Gynae- col Obstet. 2003;82:153 9. 6. Orwat S, Diller G-P, van Hagen IM, et al. Risk of pregnancy in moderate and severe aortic stenosis: from the multinational ROPAC registry. J Am Coll Cardiol. 2016;68:1727 37. 7. Tzemos N, Silversides CK, Colman JM, et al. Late cardiac outcomes af- ter pregnancy in women with congenital aortic stenosis. Am Heart J. 2009;157:474 80. 8. Arias F, Pineda J. Aortic stenosis and pregnancy. J Reprod Med. 1978;20:229 32. 9. Silversides CK, Colman JM, Sermer M, et al. Early and intermediate-term outcomes of pregnancy with congenital aortic stenosis. Am J Cardiol. 2003;91:1386 9. 10. Yap S-C, Drenthen W, Pieper PG, et al. Risk of complications dur- ing pregnancy in women with congenital aortic stenosis. Int J Cardiol. 2008;126:240 6. 11. Sugishita Y, Ito I, Kubo T. Pregnancy in cardiac patients: possible influence of volume overload by pregnancy on pulmonary circulation. Jpn Circ J. 1986;50:376 83. 12. Bryg RJ, Gordon PR, Kudesia VS, et al. Effect of pregnancy on pressure gradient in mitral stenosis. Am J Cardiol. 1989;63:384 6. 13. Palacios IF, Sanchez PL, Harrell LC, et al. Which patients benefit from percutaneous mitral balloon valvuloplasty? Prevalvuloplasty and post- valvuloplasty variables that predict long-term outcome. Circulation. 2002;105:1465 71. 14. van Hagen IM, Roos-Hesselink JW, Ruys TPE, et al. Pregnancy in women with a mechanical heart valve: data of the European Society of Cardi- ology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation. 2015;132:132 42. 15. De Santo LS, Romano G, Della Corte A, et al. Mechanical aortic valve replacement in young women planning on pregnancy: maternal and fetal outcomes under low oral anticoagulation, a pilot observational study on a comprehensive pre-operative counseling protocol. J Am Coll Cardiol. 2012;59:1110 5. 16. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC guidelines for the management of cardiovascular diseases during preg- nancy. Eur Heart J. 2018;39:3165 241. 13.1.2.2. During-Pregnancy Intervention 1. Tzemos N, Silversides CK, Colman JM, et al. Late cardiac outcomes af- ter pregnancy in women with congenital aortic stenosis. Am Heart J. 2009;157:474 80. 2. Banning AP, Pearson JF, Hall RJ. Role of balloon dilatation of the aor- tic valve in pregnant patients with severe aortic stenosis. Br Heart J. 1993;70:544 5. 3. Easterling TR, Chadwick HS, Otto CM, et al. Aortic stenosis in pregnancy. Obstet Gynecol. 1988;72:113 8. 4. Lao TT, Adelman AG, Sermer M, et al. Balloon valvuloplasty for congenital aortic stenosis in pregnancy. Br J Obstet Gynaecol. 1993;100:1141 2. 5. McIvor RA. Percutaneous balloon aortic valvuloplasty during pregnancy. Int J Cardiol. 1991;32:1 3. 6. Myerson SG, Mitchell ARJ, Ormerod OJM, et al. What is the role of balloon dilatation for severe aortic stenosis during pregnancy? J Heart Valve Dis. 2005;14:147 50. 7. Tumelero RT, Duda NT, Tognon AP, et al. Percutaneous balloon aortic valvuloplasty in a pregnant adolescent. Arq Bras Cardiol. 2004;82: 98 101. 8. McCann GP, Steadman CD, Ray SG, et al. Managing the asymptomatic patient with severe aortic stenosis: randomised controlled trials of early surgery are overdue. Heart. 2011;97:1119 21. 9. Ben Farhat M, Gamra H, Betbout F, et al. Percutaneous balloon mitral commissurotomy during pregnancy. Heart. 1997;77:564 7. 10. de Souza JA, Martinez EE Jr, Ambrose JA, et al. Percutaneous balloon mi- tral valvuloplasty in comparison with open mitral valve commissurotomy for mitral stenosis during pregnancy. J Am Coll Cardiol. 2001;37:900 3. CLINICAL STATEMENTS AND GUIDELINES 11. Glantz JC, Pomerantz RM, Cunningham MJ, et al. Percutaneous balloon valvuloplasty for severe mitral stenosis during pregnancy: a review of ther- apeutic options. Obstet Gynecol Surv. 1993;48:503 8. 12. Iung B, Cormier B, Elias J, et al. Usefulness of percutaneous balloon commissurotomy for mitral stenosis during pregnancy. Am J Cardiol. 1994;73:398 400. 13. Weiss BM, von Segesser LK, Alon E, et al. Outcome of cardiovascular sur- gery and pregnancy: a systematic review of the period 1984 1996. Am J Obstet Gynecol. 1998;179:1643 53. 14. Becker RM. Intracardiac surgery in pregnant women. Ann Thorac Surg. 1983;36:453 8. 15. Chambers CE, Clark SL. Cardiac surgery during pregnancy. Clin Obstet Gynecol. 1994;37:316 23. 16. Parry AJ, Westaby S. Cardiopulmonary bypass during pregnancy. Ann Tho- rac Surg. 1996;61:1865 9. 17. Gulraze A, Kurdi W, Niaz F, et al. Mitral balloon valvuloplasty during preg- nancy: the long term up to 17 years obstetric outcome and childhood development. Pak J Med Sci. 2014;30:86 90. 18. Vinayakumar D, Vinod GV, Madhavan S, et al. Maternal and fetal out- comes in pregnant women undergoing balloon mitral valvotomy for rheu- matic mitral stenosis. Indian Heart J. 2016;68:780 2. 19. Salome N, Dias CC, Ribeiro J, et al. Balloon mitral valvuloplasty during pregnancy our experience. Rev Port Cardiol. 2002;21:1437 44. 20. Weiss BM, von Segesser LK, Alon E, et al. Outcome of cardiovascular sur- gery and pregnancy: a systematic review of the period 1984 1996. Am J Obstet Gynecol. 1998;179:1643 53. 13.2. Prosthetic Valves in Pregnant Women 13.2.1. Initial Management 1. Samiei N, Amirsardari M, Rezaei Y, et al. Echocardiographic evaluation of hemodynamic changes in left-sided heart valves in pregnant women with valvular heart disease. Am J Cardiol. 2016;118:1046 52. 2. Goland S, Schwartzenberg S, Fan J, et al. Monitoring of anti-Xa in preg- nant patients with mechanical prosthetic valves receiving low-molecular- weight heparin: peak or trough levels? J Cardiovasc Pharmacol Ther. 2014;19:451 6. 3. Vause S, Clarke B, Tower CL, et al. Pregnancy outcomes in women with mechanical prosthetic heart valves: a prospective descriptive population based study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system. BJOG. 2017;124:1411 9. 4. van Hagen IM, Roos-Hesselink JW, Ruys TPE, et al. Pregnancy in women with a mechanical heart valve: data of the European Society of Cardi- ology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation. 2015;132:132 42. 5. D Souza R, Ostro J, Shah PS, et al. Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis. Eur Heart J. 2017;38:1509 16. 6. Steinberg ZL, Dominguez-Islas CP, Otto CM, et al. Maternal and fetal outcomes of anticoagulation in pregnant women with mechanical heart valves. J Am Coll Cardiol. 2017;69:2681 91. 7. Lancellotti P, Pibarot P, Chambers J, et al. Recommendations for the im- aging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016;17:589 90. 8. Tong AT, Roudaut R, Ozkan M, et al. Transesophageal echocardiogra- phy improves risk assessment of thrombolysis of prosthetic valve throm- bosis: results of the international PRO-TEE registry. J Am Coll Cardiol. 2004;43:77 84. 9. zkan M, akal B, Karakoyun S, et al. Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low- dose, slow infusion of tissue-type plasminogen activator. Circulation. 2013;128:532 40. 10. Alshawabkeh L, Economy KE, Valente AM. Anticoagulation during preg- nancy: evolving strategies with a focus on mechanical valves. J Am Coll Cardiol. 2016;68:1804 13. 11. Tong AT, Roudaut R, Ozkan M, et al. Transesophageal echocardiogra- phy improves risk assessment of thrombolysis of prosthetic valve throm- bosis: results of the international PRO-TEE registry. J Am Coll Cardiol. 2004;43:77 84. 12. Ozkan M, Cakal B, Karakoyun S, et al. Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low-dose, slow infusion of tissue-type plasminogen activator. Circulation. 2013;128:532 40. 13.2.2. Anticoagulation for Pregnant Women With Mechanical Prosthetic Heart Valves 1. Alshawabkeh L, Economy KE, Valente AM. Anticoagulation during preg- nancy: evolving strategies with a focus on mechanical valves. J Am Coll Cardiol. 2016;68:1804 13. 2. Samiei N, Amirsardari M, Rezaei Y, et al. Echocardiographic evaluation of hemodynamic changes in left-sided heart valves in pregnant women with valvular heart disease. Am J Cardiol. 2016;118:1046 52. 3. D Souza R, Ostro J, Shah PS, et al. Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis. Eur Heart J. 2017;38:1509 16. 4. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000;160:191 6. 5. Lawley CM, Lain SJ, Algert CS, et al. Prosthetic heart valves in pregnancy, outcomes for women and their babies: a systematic review and meta- analysis. BJOG. 2015;122:1446 55. 6. Xu Z, Fan J, Luo X, et al. Anticoagulation regimens during pregnancy in patients with mechanical heart valves: a systematic review and meta-anal- ysis. Can J Cardiol. 2016;32:1248.e1 9. 7. Batra J, Itagaki S, Egorova NN, et al. Outcomes and long-term effects of pregnancy in women with biologic and mechanical valve prostheses. Am J Cardiol. 2018;122:1738 44. 8. Yinon Y, Siu SC, Warshafsky C, et al. Use of low molecular weight hepa- rin in pregnant women with mechanical heart valves. Am J Cardiol. 2009;104:1259 63. 9. Rowan JA, McCowan LM, Raudkivi PJ, et al. Enoxaparin treatment in women with mechanical heart valves during pregnancy. Am J Obstet Gy- necol. 2001;185:633 7. 10. Abildgaard U, Sandset PM, Hammerstr m J, et al. Management of preg- nant women with mechanical heart valve prosthesis: thromboprophylaxis with low molecular weight heparin. Thromb Res. 2009;124:262 7. 11. van Hagen IM, Roos-Hesselink JW, Ruys TPE, et al. Pregnancy in women with a mechanical heart valve: data of the European Society of Cardi- ology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation. 2015;132:132 42. 12. Goland S, Schwartzenberg S, Fan J, et al. Monitoring of anti-Xa in preg- nant patients with mechanical prosthetic valves receiving low-molecular- weight heparin: peak or trough levels? J Cardiovasc Pharmacol Ther. 2014;19:451 6. 13. Elkayam U. Anticoagulation therapy for pregnant women with mechani- cal prosthetic heart valves: how to improve safety? J Am Coll Cardiol. 2017;69:2692 5. 14. Vause S, Clarke B, Tower CL, et al. Pregnancy outcomes in women with mechanical prosthetic heart valves: a prospective descriptive population based study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system. BJOG. 2017;124:1411 9. 15. Oran B, Lee-Parritz A, Ansell J. Low molecular weight heparin for the pro- phylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy. Thromb Haemost. 2004;92:747 51. 16. Steinberg ZL, Dominguez-Islas CP, Otto CM, et al. Maternal and fetal outcomes of anticoagulation in pregnant women with mechanical heart valves. J Am Coll Cardiol. 2017;69:2681 91. 17. D Souza R, Silversides CK, McLintock C. Optimal anticoagulation for pregnant women with mechanical heart valves. Semin Thromb Hemost. 2016;42:798 804. 18. Vitale N, De Feo M, De Santo LS, et al. Dose-dependent fetal complica- tions of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol. 1999;33:1637 41. 19. Meschengieser SS, Fondevila CG, Santarelli MT, et al. Anticoagulation in pregnant women with mechanical heart valve prostheses. Heart. 1999;82:23 6. 20. Sadler L, McCowan L, White H, et al. Pregnancy outcomes and cardiac complications in women with mechanical, bioprosthetic and homograft valves. BJOG. 2000;107:245 53. 21. Horlocker TT, Vandermeuelen E, Kopp SL, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Soci- ety of Regional Anesthesia and Pain Medicine evidence-based guidelines (fourth edition). Reg Anesth Pain Med. 2018;43:263 309. 22. De Santo LS, Romano G, Della Corte A, et al. Mitral mechanical re- placement in young rheumatic women: analysis of long-term survival, CLINICAL STATEMENTS AND GUIDELINES valve-related complications, and pregnancy outcomes over a 3707-pa- tient-year follow-up. J Thorac Cardiovasc Surg. 2005;130:13 9. 23. Ayad SW, Hassanein MM, Mohamed EA, et al. Maternal and fetal out- comes in pregnant women with a prosthetic mechanical heart valve. Clin Med Insights Cardiol. 2016;10:11 7. 24. Al-Lawati AAM, Venkitraman M, Al-Delaime T, et al. Pregnancy and me- chanical heart valves replacement; dilemma of anticoagulation. Eur J Car- diothorac Surg. 2002;22:223 7. 25. Hassouna A, Allam H. Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: a meta-analysis. Interact Cardiovasc Thorac Surg. 2014;18:797 806. 26. zkan M, akal B, Karakoyun S, et al. Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low- dose, slow infusion of tissue-type plasminogen activator. Circulation. 2013;128:532 40. 27. McLintock C, McCowan LME, North RA. Maternal complications and pregnancy outcome in women with mechanical prosthetic heart valves treated with enoxaparin. BJOG. 2009;116:1585 92. 28. Massel DR, Little SH. Antiplatelet and anticoagulation for patients with prosthetic heart valves. Cochrane Database Syst Rev. 2013;CD003464. 29. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran ver- sus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206 14. 30. Lameijer H, Aalberts JJJ, van Veldhuisen DJ, et al. Efficacy and safety of di- rect oral anticoagulants during pregnancy; a systematic literature review. Thromb Res. 2018;169:123 7. 31. Beyer-Westendorf J, Michalski F, Tittl L, et al. Pregnancy outcome in pa- tients exposed to direct oral anticoagulants - and the challenge of event reporting. Thromb Haemost. 2016;116:651 8. 32. Cohen H, Arachchillage DR, Middeldorp S, et al. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14:1673 6. 33. Quinn J, Von Klemperer K, Brooks R, et al. Use of high intensity adjusted dose low molecular weight heparin in women with mechanical heart valves during pregnancy: a single-center experience. Haematologica. 2009;94:1608 12. 34. James AH, Brancazio LR, Gehrig TR, et al. Low-molecular-weight heparin for thromboprophylaxis in pregnant women with mechanical heart valves. J Matern Fetal Neonatal Med. 2006;19:543 9. 35. Meschengieser SS, Fondevila CG, Santarelli MT, et al. Anticoagulation in pregnant women with mechanical heart valve prostheses. Heart. 1999;82:23 6. 36. De Santo LS, Romano G, Della Corte A, et al. Mitral mechanical replace- ment in young rheumatic women: analysis of long-term survival, valve- related complications, and pregnancy outcomes over a 3707-patient-year follow-up. J Thorac Cardiovasc Surg. 2005;130:13 9. 37. Al-Lawati AA, Venkitraman M, Al-Delaime T, et al. Pregnancy and me- chanical heart valves replacement; dilemma of anticoagulation. Eur J Car- diothorac Surg. 2002;22:223 7. 38. De Santo LS, Romano G, Della Corte A, et al. Mechanical aortic valve replace- ment in young women planning on pregnancy: maternal and fetal outcomes under low oral anticoagulation, a pilot observational study on a comprehen- sive pre-operative counseling protocol. J Am Coll Cardiol. 2012;59:1110 5. 39. McLintock C, McCowan LM, North RA. Maternal complications and preg- nancy outcome in women with mechanical prosthetic heart valves treated with enoxaparin. BJOG. 2009;116:1585 92. 40. Sillesen M, Hjortdal V, Vejlstrup N, et al. Pregnancy with prosthetic heart valves 30 years nationwide experience in Denmark. Eur J Cardiothorac Surg. 2011;40:448 54. 41. James AH, Brancazio LR, Gehrig TR, et al. Low-molecular-weight heparin for thromboprophylaxis in pregnant women with mechanical heart valves. J Matern Fetal Neonatal Med. 2006;19:543 9. heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses. J Am Coll Cardiol. 1996;27:1698 703. 43. Sbarouni E, Oakley CM. Outcome of pregnancy in women with valve pros- theses. Br Heart J. 1994;71:196 201. 44. Ozkan M, Cakal B, Karakoyun S, et al. Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low- dose, slow infusion of tissue-type plasminogen activator. Circulation. 2013;128:532 40. 45. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran ver- sus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206 14. 14. SURGICAL CONSIDERATIONS 14.1. Evaluation and Management of CAD in Patients With VHD 14.1.1. Management of CAD in Patients Undergoing TAVI 1. Bajaj A, Pancholy S, Sethi A, et al. Safety and feasibility of PCI in patients undergoing TAVR: a systematic review and meta-analysis. Heart Lung. 2017;46:92 9. 2. Chakravarty T, Sharma R, Abramowitz Y, et al. Outcomes in patients with transcatheter aortic valve replacement and left main stenting: the TAVR- LM registry. J Am Coll Cardiol. 2016;67:951 60. 3. Mohr FW, Morice M-C, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three- vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381:629 38. 4. Thalji NM, Suri RM, Daly RC, et al. The prognostic impact of concomitant coronary artery bypass grafting during aortic valve surgery: implications for revascularization in the transcatheter era. J Thorac Cardiovasc Surg. 2015;149:451 60. 5. Faroux L, Guimaraes L, Wintzer-Wehekind J, et al. Coronary artery disease and transcatheter aortic valve replacement: JACC state-of-the-art review. J Am Coll Cardiol. 2019;74:362 72. 6. Goel SS, Ige M, Tuzcu EM, et al. Severe aortic stenosis and coronary artery disease implications for management in the transcatheter aortic valve replacement era: a comprehensive review. J Am Coll Cardiol. 2013;62:1 10. 7. Sankaramangalam K, Banerjee K, Kandregula K, et al. Impact of coro- nary artery disease on 30-day and 1-year mortality in patients undergoing transcatheter aortic valve replacement: a meta-analysis. J Am Heart Assoc. 2017;6:e006092. 8. Millan-Iturbe O, Sawaya FJ, L nborg J, et al. Coronary artery disease, revascularization, and clinical outcomes in transcatheter aortic valve re- placement: real-world results from the East Denmark Heart Registry. Cath- eter Cardiovasc Interv. 2018;92:818 26. 9. Witberg G, Regev E, Chen S, et al. The prognostic effects of coronary disease severity and completeness of revascularization on mortality in pa- tients undergoing transcatheter aortic valve replacement. JACC Cardio- vasc Interv. 2017;10:1428 35. 10. Chieffo A, Giustino G, Spagnolo P, et al. Routine screening of coronary artery disease with computed tomographic coronary angiography in place of invasive coronary angiography in patients undergoing transcatheter aortic valve replacement. Circ Cardiovasc Interv. 2015;8:e002025. 11. Rossi A, De Cecco CN, Kennon SRO, et al. CT angiography to evalu- ate coronary artery disease and revascularization requirement before trans-catheter aortic valve replacement. J Cardiovasc Comput Tomogr. 2017;11:338 46. 12. van den Boogert TPW, Vendrik J, Claessen B, et al. CTCA for detection of significant coronary artery disease in routine TAVI work-up: A systematic review and meta-analysis. Neth Heart J. 2018;26:591 9. 13. Pesarini G, Scarsini R, Zivelonghi C, et al. Functional assessment of coro- nary artery disease in patients undergoing transcatheter aortic valve im- plantation: influence of pressure overload on the evaluation of lesions severity. Circ Cardiovasc Interv. 2016;9:e004088. 14. Ahmad Y, G tberg M, Cook C, et al. Coronary hemodynamics in patients with severe aortic stenosis and coronary artery disease undergoing trans- catheter aortic valve replacement: implications for clinical indices of coro- nary stenosis severity. JACC Cardiovasc Interv. 2018;11:2019 31. 15. Yamanaka F, Shishido K, Ochiai T, et al. Instantaneous wave-free ratio for the assessment of intermediate coronary artery stenosis in patients with severe aortic valve stenosis: comparison with myocardial perfusion scintig- raphy. JACC Cardiovasc Interv. 2018;11:2032 40. 14.1.2. Management of CAD in Patients Undergoing Valve Surgery 1. Graboys TB, Cohn PF. The prevalence of angina pectoris and abnormal coronary arteriograms in severe aortic valvular disease. Am Heart J. 1977;93:683 6. 2. Ramsdale DR, Bennett DH, Bray CL, et al. Angina, coronary risk factors and coronary artery disease in patients with valvular disease. A prospective study. Eur Heart J. 1984;5:716 26. CLINICAL STATEMENTS AND GUIDELINES 3. Dangas G, Khan S, Curry BH, et al. Angina pectoris in severe aortic steno- sis. Cardiology. 1999;92:1 3. 4. Basta LL, Raines D, Najjar S, et al. Clinical, haemodynamic, and coronary angiographic correlates of angina pectoris in patients with severe aortic valve disease. Br Heart J. 1975;37:150 7. 5. Thalji NM, Suri RM, Daly RC, et al. Assessment of coronary artery disease risk in 5463 patients undergoing cardiac surgery: when is preoperative coronary an- giography necessary? J Thorac Cardiovasc Surg. 2013;146:1055 63, 64.e1. 6. Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976;38:46 51. 7. Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979;300:1350 8. 8. Heidenreich PA, Kapoor JR. Radiation induced heart disease: systemic dis- orders in heart disease. Heart. 2009;95:252 8. 9. Gahl K, Sutton R, Pearson M, et al. Mitral regurgitation in coronary heart disease. Br Heart J. 1977;39:13 8. 10. Enriquez-Sarano M, Klodas E, Garratt KN, et al. Secular trends in coronary atherosclerosis analysis in patients with valvular regurgitation. N Engl J Med. 1996;335:316 22. 11. Breisblatt WM, Cerqueira M, Francis CK, et al. Left ventricular function in ischemic mitral regurgitation a precatheterization assessment. Am Heart J. 1988;115:77 82. 12. Mark DB, Berman DS, Budoff MJ, et al. ACCF/ACR/AHA/NASCI/SAIP/ SCAI/SCCT 2010 expert consensus document on coronary computed to- mographic angiography: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Car- diol. 2010;55:2663 99. 13. Opolski MP, Kim WK, Liebetrau C, et al. Diagnostic accuracy of computed tomography angiography for the detection of coronary artery disease in patients referred for transcatheter aortic valve implantation. Clin Res Car- diol. 2015;104:471 80. 14. Hamdan A, Wellnhofer E, Konen E, et al. Coronary CT angiography for the detection of coronary artery stenosis in patients referred for transcatheter aortic valve replacement. J Cardiovasc Comput Tomogr. 2015;9:31 41. 15. Andreini D, Pontone G, Mushtaq S, et al. Diagnostic accuracy of multide- tector computed tomography coronary angiography in 325 consecutive patients referred for transcatheter aortic valve replacement. Am Heart J. 2014;168:332 9. 16. Chieffo A, Giustino G, Spagnolo P, et al. Routine screening of coronary artery disease with computed tomographic coronary angiography in place of invasive coronary angiography in patients undergoing transcatheter aortic valve replacement. Circ Cardiovasc Interv. 2015;8:e002025. 17. Matsumoto S, Yamada Y, Hashimoto M, et al. CT imaging before trans- catheter aortic valve implantation (TAVI) using variable helical pitch scan- ning and its diagnostic performance for coronary artery disease. Eur Ra- diol. 2017;27:1963 70. 18. Rossi A, De Cecco CN, Kennon SRO, et al. CT angiography to evaluate coro- nary artery disease and revascularization requirement before trans-catheter aortic valve replacement. J Cardiovasc Comput Tomogr. 2017;11:338 46. 19. Thalji NM, Suri RM, Daly RC, et al. The prognostic impact of concomitant coronary artery bypass grafting during aortic valve surgery: implications for revascularization in the transcatheter era. J Thorac Cardiovasc Surg. 2015;149:451 60. 20. Byrne JG, Leacche M, Vaughan DE, et al. Hybrid cardiovascular proce- dures. JACC Cardiovasc Interv. 2008;1:459 68. 21. Pontone G, Andreini D, Bartorelli AL, et al. Feasibility and accuracy of a comprehensive multidetector computed tomography acquisition for pa- tients referred for balloon-expandable transcatheter aortic valve implanta- tion. Am Heart J. 2011;161:1106 13. 22. Lund O, Nielsen TT, Pilegaard HK, et al. The influence of coronary artery disease and bypass grafting on early and late survival after valve replace- ment for aortic stenosis. J Thorac Cardiovasc Surg. 1990;100:327 37. 23. Beach JM, Mihaljevic T, Svensson LG, et al. Coronary artery disease and outcomes of aortic valve replacement for severe aortic stenosis. J Am Coll Cardiol. 2013;61:837 48. 14.2. Intervention for AF in Patients With VHD 1. Ad N, Henry L, Hunt S, et al. Do we increase the operative risk by add- ing the Cox Maze III procedure to aortic valve replacement and coronary artery bypass surgery? J Thorac Cardiovasc Surg. 2012;143:936 44. 2. Badhwar V, Rankin JS, Damiano RJ Jr, et al. The Society of Thoracic Sur- geons 2017 clinical practice guidelines for the surgical treatment of atrial fibrillation. Ann Thorac Surg. 2017;103:329 41. 3. Ad N, Holmes SD, Pritchard G, et al. Association of operative risk with the outcome of concomitant Cox Maze procedure: a comparison of results across risk groups. J Thorac Cardiovasc Surg. 2014;148:3027 33. 4. Ad N, Holmes SD, Rongione AJ, et al. The long-term safety and efficacy of concomitant Cox maze procedures for atrial fibrillation in patients without mitral valve disease. J Thorac Cardiovasc Surg. 2019;157:1505 14. 5. Gillinov AM, Bakaeen F, McCarthy PM, et al. Surgery for paroxysmal atrial fibrillation in the setting of mitral valve disease: a role for pulmonary vein isolation? Ann Thorac Surg. 2006;81:19 26. 6. Gillinov AM, Gelijns AC, Parides MK, et al. Surgical ablation of atri- al fibrillation during mitral-valve surgery. N Engl J Med. 2015;372: 1399 409. 7. Abreu Filho CA, Lisboa LA, Dallan LA, et al. Effectiveness of the maze procedure using cooled-tip radiofrequency ablation in patients with per- manent atrial fibrillation and rheumatic mitral valve disease. Circulation. 2005;112:I20 5. 8. Akpinar B, Guden M, Sagbas E, et al. Combined radiofrequency modified maze and mitral valve procedure through a port access approach: early and mid-term results. Eur J Cardiothorac Surg. 2003;24:223 30. 9. Chua YL, Schaff HV, Orszulak TA, et al. Outcome of mitral valve repair in patients with preoperative atrial fibrillation. Should the maze proce- dure be combined with mitral valvuloplasty? J Thorac Cardiovasc Surg. 1994;107:408 15. 10. Deneke T, Khargi K, Grewe PH, et al. Efficacy of an additional MAZE pro- cedure using cooled-tip radiofrequency ablation in patients with chronic atrial fibrillation and mitral valve disease. A randomized, prospective trial. Eur Heart J. 2002;23:558 66. 11. Jessurun ER, van Hemel NM, Defauw JJ, et al. A randomized study of combining maze surgery for atrial fibrillation with mitral valve surgery. J Cardiovasc Surg (Torino). 2003;44:9 18. 12. Rankin JS, Grau-Sepulveda MV, Ad N, et al. Associations between surgical ablation and operative mortality after mitral valve procedures. Ann Thorac Surg. 2018;105:1790 6. 13. Ad N, Holmes SD, Lamont D, et al. Left-sided surgical ablation for patients with atrial fibrillation who are undergoing concomitant cardiac surgical procedures. Ann Thorac Surg. 2017;103:58 65. 14. Huffman MD, Karmali KN, Berendsen MA, et al. Concomitant atrial fibril- lation surgery for people undergoing cardiac surgery. Cochrane Database Syst Rev. 2016;CD011814. 15. Huffman MD, Malaisrie SC, Karmali KN. Concomitant atrial fibrilla- tion surgery for people undergoing cardiac surgery. JAMA Cardiol. 2017;2:334 5. 16. Friedman DJ, Piccini JP, Wang T, et al. Association between left atrial appendage occlusion and readmission for thromboembolism among patients with atrial fibrillation undergoing concomitant cardiac surgery. JAMA. 2018;319:365 74. 17. Yao X, Gersh BJ, Holmes DR Jr, et al. Association of surgical left atrial ap- pendage occlusion with subsequent stroke and mortality among patients undergoing cardiac surgery. JAMA. 2018;319:2116 26. 18. Johnsrud DO, Melduni RM, Lahr B, et al. Evaluation of anticoagulation use and subsequent stroke in patients with atrial fibrillation after empiric surgical left atrial appendage closure: A retrospective case-control study. Clin Cardiol. 2018;41:1578 82. 19. Abrich VA, Narichania AD, Love WT, et al. Left atrial appendage exclusion during mitral valve surgery and stroke in atrial fibrillation. J Interv Card Electrophysiol. 2018;53:285 92. 20. Garc a-Fern ndez MA, P rez-David E, Quiles J, et al. Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis: a transesophageal echocardiographic study. J Am Coll Cardiol. 2003;42:1253 8. 21. Noseworthy PA, Yao X, Deshmukh AJ, et al. Patterns of anticoagulation use and cardioembolic risk after catheter ablation for atrial fibrillation. J Am Heart Assoc. 2015;4:e002597. 22. Eitel C, Koch J, Sommer P, et al. Novel oral anticoagulants in a real-world cohort of patients undergoing catheter ablation of atrial fibrillation. Euro- pace. 2013;15:1587 93. 23. Melduni RM, Schaff HV, Lee H-C, et al. Impact of left atrial appendage clo- sure during cardiac surgery on the occurrence of early postoperative atrial fibrillation, stroke, and mortality: a propensity score-matched analysis of 10633 patients. Circulation. 2017;135:366 78. CLINICAL STATEMENTS AND GUIDELINES 15. NONCARDIAC SURGERY IN PATIENTS WITH VHD 15.1. Diagnosis of Patients With VHD Undergoing Noncardiac Surgery 1. Liu JB, Liu Y, Cohen ME, et al. Defining the intrinsic cardiac risks of opera- tions to improve preoperative cardiac risk assessments. Anesthesiology. 2018;128:283 92. 2. Wijeysundera DN, Pearse RM, Shulman MA, et al. Assessment of function- al capacity before major non-cardiac surgery: an international, prospective cohort study. Lancet. 2018;391:2631 40. 3. Dakik HA, Chehab O, Eldirani M, et al. A new index for pre-operative cardiovascular evaluation. J Am Coll Cardiol. 2019;73:3067 78. 4. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:e521 643. 5. Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/HFSA/ HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocar- diography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiog- raphy, American Heart Association, American Society of Nuclear Cardi- ology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, So- ciety for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2011;24:229 67. 15.2. Management of the Symptomatic Patient 1. Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guide- line on perioperative cardiovascular evaluation and management of pa- tients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:e278 333. 2. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:e521 643. 3. Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic- valve replacement with a self-expanding prosthesis. N Engl J Med. 2014;370:1790 8. 4. Reardon MJ, Adams DH, Kleiman NS, et al. 2-Year outcomes in patients undergoing surgical or self-expanding transcatheter aortic valve replace- ment. J Am Coll Cardiol. 2015;66:113 21. 5. Thyregod HGH, Steinbr chel DA, Ihlemann N, et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic valve ste- nosis: 1-year results from the all-comers NOTION randomized clinical trial. J Am Coll Cardiol. 2015;65:2184 94. 6. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aor- tic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374:1609 20. 7. Thourani VH, Kodali S, Makkar RR, et al. Transcatheter aortic valve re- placement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet. 2016;387:2218 25. 8. Okuno T, Yahagi K, Horiuchi Y, et al. The role of transcatheter aor- tic valve replacement in the patients with severe aortic stenosis re- quiring major non-cardiac surgery. Cardiovasc Interv Ther. 2019; 34:345 51. 9. Kogoj P, Devjak R, Bunc M. Balloon aortic valvuloplasty (BAV) as a bridge to aortic valve replacement in cancer patients who require urgent non- cardiac surgery. Radiol Oncol. 2014;48:62 6. 10. Calicchio F, Guarracino F, Giannini C, et al. Balloon aortic valvuloplasty before noncardiac surgery in severe aortic stenosis: a single-center experi- ence. J Cardiovasc Med (Hagerstown). 2017;18:109 13. 11. Kennon S, Archbold A. Expert opinion: guidelines for the management of patients with aortic stenosis undergoing non-cardiac surgery: out of date and overly prescriptive. Interv Cardiol. 2017;12:133 6. 15.3. Management of the Asymptomatic Patient 1. Agarwal S, Rajamanickam A, Bajaj NS, et al. Impact of aortic stenosis on postoperative outcomes after noncardiac surgeries. Circ Cardiovasc Qual Outcomes. 2013;6:193 200. 2. Zahid M, Sonel AF, Saba S, et al. Perioperative risk of noncardiac surgery associated with aortic stenosis. Am J Cardiol. 2005;96:436 8. 3. Tashiro T, Pislaru SV, Blustin JM, et al. Perioperative risk of major non- cardiac surgery in patients with severe aortic stenosis: a reappraisal in contemporary practice. Eur Heart J. 2014;35:2372 81. 4. Bajaj NS, Agarwal S, Rajamanickam A, et al. Impact of severe mitral regur- gitation on postoperative outcomes after noncardiac surgery. Am J Med. 2013;126:529 35. 5. Lai H-C, Lai H-C, Lee W-L, et al. Mitral regurgitation complicates postop- erative outcome of noncardiac surgery. Am Heart J. 2007;153:712 7. 6. Meyer S, McLaughlin VV, Seyfarth H-J, et al. Outcomes of noncardiac, nonobstetric surgery in patients with PAH: an international prospective survey. Eur Respir J. 2013;41:1302 7. 7. Klinger JR, Elliott CG, Levine DJ, et al. Therapy for pulmonary arterial hy- pertension in adults: update of the CHEST guideline and expert panel report. Chest. 2019;155:565 86. 8. Lai H-C, Lai H-C, Lee W-L, et al. Impact of chronic advanced aortic regur- gitation on the perioperative outcome of noncardiac surgery. Acta Anaes- thesiol Scand. 2010;54:580 8. 9. Goertz AW, Lindner KH, Seefelder C, et al. Effect of phenylephrine bolus administration on global left ventricular function in patients with coronary artery disease and patients with valvular aortic stenosis. Anesthesiology. 1993;78:834 41. 10. Goertz AW, Lindner KH, Sch tz W, et al. Influence of phenylephrine bolus administration on left ventricular filling dynamics in patients with coronary artery disease and patients with valvular aortic stenosis. Anesthesiology. 1994;81:49 58. 11. Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guide- line on perioperative cardiovascular evaluation and management of pa- tients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:e278 333. 12. Christ M, Sharkova Y, Geldner G, et al. Preoperative and perioperative care for patients with suspected or established aortic stenosis facing non- cardiac surgery. Chest. 2005;128:2944 53. 13. O Keefe JHJ, Shub C, Rettke SR. Risk of noncardiac surgical procedures in patients with aortic stenosis. Mayo Clin Proc. 1989;64:400 5. 14. Ho MC, Beathe JC, Sharrock NE. Hypotensive epidural anesthesia in pa- tients with aortic stenosis undergoing total hip replacement. Reg Anesth Pain Med. 2008;33:129 33. 15. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:e521 643. 16. Mittnacht AJ, Fanshawe M, Konstadt S. Anesthetic considerations in the patient with valvular heart disease undergoing noncardiac surgery. Semin Cardiothorac Vasc Anesth. 2008;12:33 59. 17. Frogel J, Galusca D. Anesthetic considerations for patients with advanced valvular heart disease undergoing noncardiac surgery. Anesthesiol Clin. 2010;28:67 85. 18. Smilowitz NR, Armanious A, Bangalore S, et al. Cardiovascular outcomes of patients with pulmonary hypertension undergoing noncardiac surgery. Am J Cardiol. 2019;123:1532 7. 16. EVIDENCE GAPS AND FUTURE DIRECTIONS 16.1. Prevention of Valve Disease: Stage A 1. Nazarzadeh M, Pinho-Gomes A-C, Smith Byrne K, et al. Systolic blood pressure and risk of valvular heart disease: a mendelian randomization study. JAMA Cardiol. 2019;4:788 95. 2. Lindman BR, Clavel M-A, Mathieu P, et al. Calcific aortic stenosis. Nat Rev Dis Primers. 2016;2:16006. 3. Lindman BR. Aortic stenosis: moving from treatment to prevention. J Am Coll Cardiol. 2017;69:1533 5. CLINICAL STATEMENTS AND GUIDELINES 4. Atkins SK, Aikawa E. Valve under the microscope: shining a light on emerging technologies elucidating disease mechanisms. Heart. 2019;105:1610 1. 5. Peeters FECM, Meex SJR, Dweck MR, et al. Calcific aortic valve stenosis: hard disease in the heart: a biomolecular approach towards diagnosis and treatment. Eur Heart J. 2018;39:2618 24. 6. Carapetis JR. Rheumatic heart disease in developing countries. N Engl J Med. 2007;357:439 41. 7. Soler-Soler J, Galve E. Worldwide perspective of valve disease. Heart. 2000;83:721 5. 8. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368:1005 11. 9. Go AS, Mozaffarian D, Roger VL, et al. Executive summary: heart disease and stroke statistics 2013 update: a report from the American Heart As- sociation. Circulation. 2013;127:143 52. 10. Hagler MA, Hadley TM, Zhang H, et al. TGF- signalling and reactive oxy- gen species drive fibrosis and matrix remodelling in myxomatous mitral valves. Cardiovasc Res. 2013;99:175 84. 11. Miller JD, Weiss RM, Heistad DD. Calcific aortic valve stenosis: methods, models, and mechanisms. Circ Res. 2011;108:1392 412. 12. Lindman BR, Arnold SV, Bagur R, et al. Priorities for patient-centered re- search in valvular heart disease: a report from the National Heart, Lung, and Blood Institute Working Group. J Am Heart Assoc. 2020;9:e015975. 16.2. Medical Therapy to Treat or Prevent Disease Progression: Stage B 1. Park SJ, Dweck MR. Multimodality imaging for the assessment of severe aortic stenosis. J Cardiovasc Imaging. 2019;27:235 46. 2. Everett RJ, Dweck MR. Renin-angiotensin system inhibition in aortic ste- nosis: thinking beyond transcatheter aortic valve replacement. J Am Coll Cardiol. 2019;74:642 4. 3. Lindman BR, Otto CM, Douglas PS, et al. Blood pressure and arterial load after transcatheter aortic valve replacement for aortic stenosis. Circ Car- diovasc Imaging. 2017;10:e006308. 4. Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368:503 12. 5. Lindman BR, Arnold SV, Bagur R, et al. Priorities for patient-cen- tered research in valvular heart disease: a report from the National Heart, Lung, and Blood Institute Working Group. J Am Heart Assoc. 2020;9:e015975. 16.3. Optimal Timing of Intervention: Stage C 1. Nicolau S, Ionescu T, Cleanoveanu G, et al. [National system for the reg- istration of congenital malformations and genetic diseases] [Article in Ro- manian]. Rev Pediatr Obstet Ginecol Pediatr. 1987;36:193 215. 2. Campo J, Tsoris A, Kruse J, et al. Prognosis of severe asymptomatic aortic stenosis with and without surgery. Ann Thorac Surg. 2019;108:74 9. 3. Kataruka A, Otto CM. Valve durability after transcatheter aortic valve im- plantation. J Thorac Dis. 2018;10:S3629 S36. 4. Lindman BR, Arnold SV, Bagur R, et al. Priorities for patient-centered re- search in valvular heart disease: a report from the National Heart, Lung, and Blood Institute Working Group. J Am Heart Assoc. 2020;9:e015975. 16.4. Better Options for Intervention: Stage D 1. Otto CM. Informed shared decisions for patients with aortic stenosis. N Engl J Med. 2019;380:1769 70. 2. Lindman BR, Clavel M-A, Mathieu P, et al. Calcific aortic stenosis. Nat Rev Dis Primers. 2016;2:16006. 3. Lindman BR, Arnold SV, Bagur R, et al. Priorities for patient-centered re- search in valvular heart disease: a report from the National Heart, Lung, and Blood Institute Working Group. J Am Heart Assoc. 2020;9:e015975. Appendix 1. Author Relationships With Industry and Other Entities (Relevant) 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section Catherine M. Otto (Co-Chair) University of Washington J. Ward Kennedy-Hamilton Endowed Chair in Cardiology and Professor of Medicine None None None None None None None Rick A. Nishimura (Co-Chair) Mayo Clinic Department of Cardiovascular Medicine and Judd and Mary Morris Leighton Professor of Cardiovascular Diseases and Hypertension None None None None None None None Robert O. Bonow Northwestern University, Feinberg School of Medicine Vice Chair for Development and Innovation, Department of Medicine; Max and Lilly Goldberg Distinguished Professor of Cardiology; and Professor of Medicine None None None None None None None Blase A. Carabello East Carolina Heart Institute at East Carolina University Professor and Chief, Division of Cardiology None None None Edwards Lifesciences (DSMB) John P. Erwin III Clinical Department Chair of Internal Medicine, NorthShore University Health System Clinical Professor, University of Chicago Pritzker School of Medicine None None None None None None None (Continued) CLINICAL STATEMENTS AND GUIDELINES Federico Gentile Centro Cardiologico Gentile, Naples, Italy None None None None None None None Hani Jneid Baylor College of Medicine Associate Professor of Medicine; The Michael DeBakey VA Medical Center Director of Interventional Cardiology Research None None None None None None None Eric V. Krieger University of Washington, School of Medicine Associate Professor of Medicine; Director, Seattle Adult Congenital Heart Disease Service None None None None None None None Michael Mack Baylor Scott & White Health Chair, Cardiovascular Service line None None None Abbott Vascular Edwards Lifesciences Medtronic Christopher McLeod Mayo Clinic Clinical Director for Cardiovascular Medicine (Jacksonville, FL) None None None None None None None Patrick T. O Gara Watkins Family Distinguished Chair in Cardiology, Brigham and Women s Hospital: Professor of Medicine Harvard Medical School None None None None Edwards Scientific Medtronic Vera H. Rigolin Northwestern University, Feinberg School of Medicine Professor of Medicine (Cardiology) None None AstraZeneca Merck/ Schering- Plough* Pfizer* Thoralf M. Sundt III Massachusetts General Hospital Chief, Division of Cardiac Surgery; Co-Director, Corrigan Minehan Heart Center None None None Thrasos* Edwards Lifesciences Medtronic Annemarie Thompson Duke University Medical Center Professor of Anesthesiology, Medicine, and Population Health Sciences, Director, Anesthesiology Residency Program None None None None None None None Christopher Toly Simulab Corporation Chief Executive Officer, Chief Technology Officer None None None None None None None This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document. These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the Writing Committee during the document development process. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% of the voting stock or share of the business entity, or ownership of $5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Please refer to https://www.acc. org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees. *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. Significant relationship. This disclosure was entered under the Clinical Trial Enroller category in ACC s disclosure system. To appear in this category, the author acknowledges that there is no direct or institutional relationship with the trial sponsor as defined in the (ACCF or ACC/AHA) Disclosure Policy for Writing Committees. ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; DSMB, Data and Safety Monitoring Board; FL, Florida; and VA, Veterans Affairs. Appendix 1. Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section CLINICAL STATEMENTS AND GUIDELINES Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive) 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Abigail M. Khan Official Reviewer AHA Oregon Health and Science University None None None None None None Andrew R. Waxler Official Reviewer Board of Governors Alternate Penn State Health None Amarin* Sanofi Regeron* None None DalCor Pharmaceutical Medicines Company Penn State St Joseph Medical Center Foundation Board Member Penn State St. Joseph Medical Center Pharmacy and Therapeutics Committee Member Pfizer Inc Regeneron Sanofi None Daniel M. Shindler Official Reviewer ACC Board of Governors University of Medicine and Dentistry, Robert Wood Johnson Medical School, New Brunswick, New Jersey None None None None None None William A. Zoghbi Official Reviewer ACC Clinical Policy Approval Committee Houston Methodist- Chairman, Department of Cardiology None None None None None None Y. Joseph Woo Content Reviewer Joint Committee on Clinical Practice Guidelines Stanford University School of Medicine None None None None NIH* None Adrian F. Hernandez Content Reviewer Joint Committee on Clinical Practice Guidelines Duke University School of Medicine Amgen Inc. AstraZeneca Pharmaceuticals Bayer Corporation U.S. Biofourmis Boehringer Ingelheim Pharmaceuticals, Inc Boston Scientific* Merck and Co., Inc. Novartis* Pfizer Relypsa Sanofi-Aventis* Xogenex None None American Regent AstraZeneca* Daiichi Sankyo Genentech, Inc Glaxo Smith Kline* Merck and Co., Inc. NIH Novartis* PCORI Verily* Eidos (DSMB) AHA Defendant, patent dispute, Anastasia L. Armbruster Content Reviewer Joint Committee on Clinical Practice Guidelines St. Louis College of Pharmacy None AstraZeneca Pharmaceuticals None None None None Andrew M. Kates Content Reviewer ACC/AHA Washington University School of Medicine- Professor of Medicine Director, Cardiovascular Fellowship Program None None None None None None Andrew Wang Official Reviewer AHA Duke University Medical Center-Professor of Medicine American College of Physicians* Cytokinetics RioVant UpToDate None None Myokardia* Abbott Vascular AHA, Circulation Journal* Medtronic MyoKardia, Inc Defendant, Diagnosis of Infective Endocarditis, Anita Deswal Content Reviewer Joint Committee on Clinical Practice Guidelines The University of Texas MD Anderson Cancer Center Department Chair, Cardiology, Ting Tsung and Wei Fong Chao Distinguished Chair, Professor of Medicine None None None NIH* ACC AHA Heart Failure Society of America None Ann Bolger Content Reviewer ACC/AHA University of California, San Francisco-Professor of Medicine General Electric None None None None None (Continued) CLINICAL STATEMENTS AND GUIDELINES (Continued) Brian R. Lindman Content Reviewer ACC/AHA Vanderbilt University Medical Center None None None Edwards Lifesciences* None None Bulent Gorenek Content Reviewer Joint Committee on Clinical Practice Guidelines Eskisehir Osmangazi University School of Medicine Professor of Cardiology AstraZeneca Sandoz None None None None None Carole A. Warnes Content Reviewer ACC/AHA Mayo Clinic-Professor of Medicine None None None None None None Cheryl Batzing Content Reviewer ACC/AHA Lay Reviewer Church Ministries International Donor Relations Manager None None None None None None Christine C. Rekash Content Reviewer ACC/AHA Lay Reviewer U.S. Department of Justice Paralegal Heart Valve Voice Advocate Good Samaritan Hospital AHA Bluhm Cardiovascular Institute at Northwestern Hospital None None Edwards Life Sciences Heart Valve Voice PCORI None Daniel B. Mark Content Reviewer Joint Committee on Clinical Practice Guidelines Duke Clinical Research Institute Professor of Medicine None None None HeartFlow* Merck and Co., Inc.* Merck and Co., Inc.* None Dave L. Dixon Content Reviewer Joint Committee on Clinical Practice Guidelines Virginia Commonwealth University School of Pharmacy None None None Centers for Disease Control and Prevention* Community Pharmacy Foundation* Accreditation Council for Clinical Lipidology American Pharmacists Association American College of Pharmacy Cardiology Practice Research Network National Lipid Association None David H. Adams Content Reviewer ACC/AHA Mt. Sinai Medical Center None None None Abbott Medtronic NeoChord Edwards Lifesciences* Medtronic* None David E. Newby Content Reviewer ACC/AHA University of Edinburgh Chancellor s Building Professor of Cardiology AstraZeneca* Bristol-Myers Squibb Company* CellProthera Eli-Lilly Glaxo Smith Kline* Jansen Oncoarendi Pfizer Reckitt Benckiser Pharmaceuticals Inc. Roche Toshiba None None AstraZeneca* Boehringer Ingelheim* Bristol-Myers Squibb Company* GlaxoSmithKline* Merck and Co., Inc.* Pfizer* UCB Inc. (DSMB) AstraZeneca Pharmaceuticals Bristol-Myers Squibb Company CellProthera Esperion Infraredx None Jacqueline E. Tamis-Holland Content Reviewer Joint Committee on Clinical Practice Guidelines Mount Sinai Saint Luke s Hospital None None None Internal- Minneapolis Heart Institute-North American Covid STEMI Registry Abbott Vascular AHA Bronx Lebanon Hospital, Cardiology Fellowship Program Director Medscape/Heart. org Merck and Co., Inc. NIH The NGS Predict Study None Appendix 2. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness CLINICAL STATEMENTS AND GUIDELINES Jeanne M. DeCara Content Reviewer ACC/AHA University of Chicago Medicine None None None None Intersocietal Accreditation Commission None Jos A. Joglar Content Reviewer Joint Committee on Clinical Practice Guidelines UT Southwestern Medical Center Professor, Internal Medicine. Program Director, Clinical Cardiac Electrophysiology Fellowship Program Professor None None None None None None Joseph Edward Marine Content Reviewer Joint Committee on Clinical Practice Guidelines Johns Hopkins University School of Medicine ACC* None None None UpToDate None Kim K. Birtcher Content Reviewer Joint Committee on Clinical Practice Guidelines University of Washington Director, Adult Congenital Heart Disease Program Jones & Bartlett Learning None None None None None Larry M. Baddour Content Reviewer ACC/AHA Mayo Clinic, Rochester, MN Boston Scientific* None None None UpToDate, Inc.* None Latha Palaniappan Content Reviewer Joint Committee on Clinical Practice Guidelines Stanford Medicine 23 and me National Minority Cardiovascular Alliance None None NIH* None None Lisa de las Fuentes Content Reviewer Joint Committee on Clinical Practice Guidelines Washington University, School of Medicine, Department of Medicine, Cardiovascular Division Acceleron Altavant Arena Bayer Healthcare Pharmaceuticals Express Scripts Johnson & Johnson Mentor Planning and Consulting Phase Bio V-wave WebMD, LLC* Bayer Healthcare Pharmaceuticals* Simply Speaking* None Acceleron* Altavant* Bayer Healthcare Pharmaceuticals Complexa* Johnson & Johnson* Liquidia* Medtronic* NIH* Reata Trio Analytics* United Therapeutics* University of Kentucky (DSMB) University of Toronto ACC AHA Circulation Journals, Editorial Board Ironwood Pulmonary Hypertension Association* None Mariann Piano Content Reviewer Joint Committee on Clinical Practice Guidelines Vanderbilt University None None None None None None Mark Reisman Content Reviewer ACC/AHA University of Washington Medical Center-Section Head, Interventional Cardiology Boston Scientific None None None None None Milind Y. Desai Content Reviewer ACC/AHA Cleveland Clinic None None None None None None Patrick Collier Content Reviewer AHA Cleveland Clinic None None None None None None Philippe Pibarot Content Reviewer ACC/AHA Professor, Department of Medicine, Laval University Head of Cardiology Research, Institut Universitaire de Cardiologie et de Pneumologie de Qu bec / Qu bec Heart & Lung Institute None None None Canadian Institutes of Health Research* Cardiac Phoenix* Edwards Lifesciences* Medtronic* V-Wave Ltd.* None None Rebecca T. Hahn Content Reviewer ACC Professor of Medicine at Columbia University Medical Center Edwards Lifesciences Medtronic Philips Healthcare Abbott Vascular Baylis Medical Siemens Healthineers NaviGate None Director of the Echo Core Lab None (Continued) Appendix 2. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness CLINICAL STATEMENTS AND GUIDELINES Sandra Lauck Content Reviewer ACC/AHA University of British Columbia, Vancouver, Canada None Abbott Edwards Lifesciences* None None None None Suzanne Arnold Content Reviewer ACC/AHA St. Luke s Mid America Heart Institute None None None None Abbott Laboratories None Terrence D. Welch Content Reviewer ACC/AHA Dartmouth-Hitchcock Medical Center None None None None None None Vinod H. Thourani Content Reviewer ACC Piedmont Heart Institute Abbott Vascular Boston Scientific Edwards Lifesciences Gore Medical Jenavalve None None None Abbott Medical Medtronic None Wendy Tsang Content Reviewer ACC/AHA Toronto General Hospital UpToDate None None Heart and Stroke Foundation of Canada* Peter Munk Cardiac Center Innovation Committee* Heart and Stroke Foundation of Canada* None William F. Armstrong Content Reviewer ACC/AHA University of Michigan Professor of Medicine, Division of Cardiovascular Disease None None None None None Defendant, medical malpractice, William Schuyler Jones Content Reviewer Joint Committee on Clinical Practice Guidelines Duke University Health System Bayer Healthcare Pharmaceuticals* Janssen Pharmaceuticals, Inc* None None Bristol Myers Squibb PCORI None None Zachary D. Goldberger Content Reviewer Joint Committee on Clinical Practice Guidelines University of Wisconsin School of Medicine and Public Health, Associate Professor of Medicine None None None None None None Stephan Windecker Content Reviewer ACC/AHA Inselspital Universit tsspital Bern Direktor und Chefarzt, Universit tsklinik f r Kardiologie None None None None Abbott* Amgen* Bayer* Biotronik* Boston Scientific* Bristol-Myers Squibb CSL Behring Edwards Lifesciences* Medtronic* Polares Medical SINO Medical Technologies, Inc None This table represents all relationships of reviewers with industry and other entities that were reported at the time of peer review, including those not deemed to be relevant to this document, at the time this document was under review. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% of the voting stock or share of the business entity, or ownership of $5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Names are listed in alphabetical order within each category of review. Please refer to https://www.acc.org/guidelines/about-guidelines- and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees. *Significant relationship. No financial benefit. ACC indicates American College of Cardiology; AHA, American Heart Association; DSMB, Data and Safety Monitoring Board; NIH, National Institutes of Health; PCORI, Patient-Centered Outcomes Research Institute; and UT, University of Texas. Appendix 2. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness