Mitral regurgitation: etiology, pathogenesis, diagnosis, and outcomes

Managing a patient with mitral regurgitation (MR) is a difficult task. Degenerative and ischemic changes are the main causes of MR in developed countries, while rheumatic valve changes predominates in developing countries. MR progression occurs gradually and often imperceptibly, which is associated with the compensatory mechanisms of the heart, and leads to left ventricular remodeling and worsens prognosis. The clinical improvement in the patient condition with acute MR after the appearance of heart failure signs is obviously due to a gradual increase in the left atrium and atrial pressure decrease. The initial assessment of MR suggests the presence of heart failure clinical symptoms, which develop as MR volume increases and left ventricular systolic dysfunction worsens. However, these data are insufficient to determine the indications for surgery. Echocardiographic methods should be used to quantify the severity of the defect. The only proven treatment to improve symptoms and prevent heart failure is surgery. The annual mortality rates for surgical treatment in patients aged 50 years and older are about 3% for moderate and 6% for severe MR. Valve-preserving operations are superior in results to prosthetics and reduce mortality in patients with severe organic MR by 70%. The morphology of the valve apparatus lesion is crucial for the successful operation. The consequences of severe rheumatic valve damage limit the possibility of valve repair. If it is impossible to perform valve repair, it is preferable to perform prosthetics of the valve while maintaining the subvalvular apparatus. The best short-term and long-term results of surgical treatment were obtained in asymptomatic patients operated in specialized centers. This highlights the importance of MR early detection and assessment.

1. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on valvular heart disease. Eur Heart J. 2003;24(13):1231-43. DOI:10.1016/S0195-668X(03)00201-X.

2. Enriquez-Sarano M, Akins CW, Vahanian A. Mitral regurgitation. Lancet. 2009;373(9672):1382-94. DOI:10.1016/S0140-6736(09)60692-9.

3. Bokeria LA, Gudkova RG. Cardiovascular surgery — 2012. Diseases and congenital anomalies of the circulatory system. Moscow: AN Bakulev National Research Center of the Russian Academy of Medical Sciences; 2013. (In Russ.)

4. Anyanwu AC, Adams DH. Etiologic Classification of Degenerative Mitral Valve Disease: Barlow’s Disease and Fibroelastic Deficiency. Semin Thorac Cardiovasc Surg. 2007;19(2):90-6. DOI:10.1053/j.semtcvs.2007.04.002.

5. Nishimura RA, Vahanian A, Eleid MF, Mack MJ. Mitral valve disease — сurrent management and future challenges. Lancet. 2016;387(10025):1324-34. DOI:10.1016/S0140-6736(16)00558-4.

6. El Sabbagh A, Reddy YNV, Nishimura RA. Mitral Valve Regurgitation in the Contemporary Era: Insights Into Diagnosis, Management, and Future Directions. JACC Cardiovasc Imaging. 2018;11(4):628-43. DOI:10.1016/j.jcmg.2018.01.009.

7. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease. Circulation. 2021;143(5):e72-227. DOI:10.1161/CIR.0000000000000932.

8. Trichon BH, Felker GM, Shaw LK, et al. Relation of frequency and severity of mitral regurgitation to survival among patients with left ventricular systolic dysfunction and heart failure. Am J Cardiol. 2003;91(5):538-43. DOI:10.1016/S0002-9149(02)03301-5.

9. Baumgartner H, Falk V, Bax JJ, et al.; ESC Scientific Document Group. 2017 ESC/ EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017;38(36):2739-91. DOI:10.1093/eurheartj/ehx391.

10. Olson LJ, Subramanian R, Ackermann DM, et al. Surgical Pathology of the Mitral Valve: A Study of 712 Cases Spanning 21 Years. Mayo Clin Proc. 1987;62(1):22-34. DOI:10.1016/S0025-6196(12)61522-5.

11. David TE, Armstrong S, Sun Z, Daniel L. Late results of mitral valve repair for mitral regurgitation due to degenerative disease. Ann Thorac Surg. 1993;56(1):7-14. DOI:10.1016/0003-4975(93)90396-Y.

12. Barlow JB, Pocock WA. The significance of late systolic murmurs and mid-late systolic clicks. Md State Med J. 1963;12:76-7.

13. Kishon Y, Oh JK, Schaff HV, et al. Mitral Valve Operation in Postinfarction Rupture of a Papillary Muscle: Immediate Results and Long-Term Follow-Up of 22 Patients. Mayo Clin Proc. 1992;67(11):1023-30. DOI:10.1016/S0025-6196(12)61116-1.

14. Acar C, de Ibarra JS, Lansac E. Anterior leaflet augmentation with autologous pericardium for mitral repair in rheumatic valve insufficiency. J Heart Valve Dis. 2004;13(5):741-6.

15. Roldan CA, Shively BK, Lau CC, et al. Systemic lupus erythematosus valve disease by transesophageal echocardiography and the role of antiphospholipid antibodies. J Am Coll Cardiol. 1992;20(5):1127-34. DOI:10.1016/0735-1097(92)90368-W.

16. Lund MB, Ihlen H, Voss BMR, et al. Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin’s disease: an echocardiographic study. Heart. 1996;75(6):591-5. DOI:10.1136/hrt.75.6.591.

17. Enriquez-Sarano M, Seward JB, Bailey KR, Tajik AJ. Effective regurgitant orifice area: a noninvasive Doppler development of an old hemodynamic concept. J Am Coll Cardiol. 1994;23(2):443-51. DOI:10.1016/0735-1097(94)90432-4.

18. Yellin EL, Yoran C, Sonnenblick EH, et al. Dynamic changes in the canine mitral regurgitant orifice area during ventricular ejection. Circ Res. 1979;45(5):677-83. DOI:10.1161/01.RES.45.5.677.

19. Schwammenthal E, Chen C, Benning F, et al. Dynamics of mitral regurgitant flow and orifice area. Physiologic application of the proximal flow convergence method: clinical data and experimental testing. Circulation. 1994;90(1):307-22. DOI:10.1161/01.CIR.90.1.307.

20. Enriquez-Sarano M, Basmadjian AJ, Rossi A, et al. Progression of mitral regurgitation: a prospective Doppler echocardiographic study. J Am Coll Cardiol. 1999;34(4):1137-44. DOI:10.1016/S0735-1097(99)00313-7.

21. Lutra A. Echo-KG in simple terms. Practical Medicine. 2017. (In Russ.)

22. Flachsсkampf F, Sandrikov VA. Practical echocardiography. Guide to echocardiographic diagnosis. Moscow; 2013. (In Russ.)

23. Grigioni F, Enriquez-Sarano M, Zehr KJ, et al. Ischemic mitral regurgitation: Longterm outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103(13):1759-64. DOI:10.1161/01.CIR.103.13.1759.

24. Tolstikhina AA, Levin VI. Analysis of parameters of mitral valve insufficiency assessment: clinical application. Medical Alphabet. 2018;4(37):51-6 (In Russ.)

25. Vahanian A, Beyersdorf F, Praz F, et al.; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022;43(7):561-632. DOI:10.1093/eurheartj/ehab395. Erratum in: Eur Heart J. 2022;43(21):2022. DOI:10.1093/eurheartj/ehac051.

26. de Groot-De Laat LE, McGhie J, Ren B, et al. A modified echocardiographic classification of mitral valve regurgitation mechanism: The role of three-dimensional echocardiography. J Cardiovasc Imaging. 2019;27(3):189-99. DOI:10.4250/jcvi.2019.27.e29.

27. Kim HM, Cho GY, Hwang IC, et al. Myocardial Strain in Prediction of Outcomes After Surgery for Severe Mitral Regurgitation. JACC Cardiovasc Imaging. 2018;11(9):1235-44. DOI:10.1016/j.jcmg.2018.03.016.

28. Ling LH, Enriquez-Sarano M, Seward JB, et al. Clinical Outcome of Mitral Regurgitation Due to Flail Leaflet. N Engl J Med. 1996;335(19):1417-23. DOI:10.1056/NEJM199611073351902.

29. Grigioni F, Enriquez-Sarano M, Ling LH, et al. Sudden death in mitral regurgitation due to flail leaflet. J Am Coll Cardiol. 1999;34(7):2078-85. DOI:10.1016/S0735-1097(99)00474-X.

30. Kligfield P, Hochreiter C, Niles N, et al. Relation of sudden death in pure mitral regurgitation, with and without mitral valve prolapse, to repetitive ventricular arrhythmias and right and left ventricular ejection fractions. Am J Cardiol. 1987;60(4):397-9. DOI:10.1016/0002-9149(87)90261-X.

31. Avierinos JF, Gersh BJ, Melton LJ 3rd, et al. Natural history of asymptomatic mitral valve prolapse in the community. Circulation. 2002;106(11):1355-61. DOI:10.1161/01.CIR.0000028933.34260.09.

32. Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, et al. Quantitative Determinants of the Outcome of Asymptomatic Mitral Regurgitation. N Engl J Med. 2005;352(9):875-83. DOI:10.1056/NEJMoa041451.

33. Avierinos JF, Brown RD, Foley DA, et al. Cerebral ischemic events after diagnosis of mitral valve prolapse: A community-based study of incidence and predictive factors. Stroke. 2003;34(6):1339-44. DOI:10.1161/01.STR.0000072274.12041.FF.

34. Sutton TM, Stewart RAH, Gerber IL, et al. Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation. J Am Coll Cardiol. 2003;41(12):2280-7. DOI:10.1016/S0735-1097(03)00486-8.

35. Grigioni F, Avierinos JF, Ling LH, et al. Atrial fibrillation complicating the course of degenerative mitral regurgitation: Determinants and long-term outcome. J Am Coll Cardiol. 2002;40(1):84-92. DOI:10.1016/S0735-1097(02)01922-8.

36. Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for Evaluation of the Severity of Native Valvular Regurgitation with Two-dimensional and Doppler Echocardiography. J Am Soc Echocardiogr. 2003;16(7):777-802. DOI:10.1016/S0894-7317(03)00335-3.

37. Ahmed MI, Aban I, Lloyd SG, et al. A randomized controlled phase IIb trial of beta(1)-receptor blockade for chronic degenerative mitral regurgitation. J Am Coll Cardiol. 2012;60(9):833-8. DOI:10.1016/j.jacc.2012.04.029.

38. Varadarajan P, Joshi N, Appel D, et al. Effect of Beta-blocker therapy on survival in patients with severe mitral regurgitation and normal left ventricular ejection fraction. Am J Cardiol. 2008;102(5):611-5. DOI:10.1016/j.amjcard.2008.04.029.

39. Lazam S, Vanoverschelde JL, Tribouilloy C, et al.; MIDA (Mitral Regurgitation International Database) Investigators. Twenty-Year Outcome after Mitral Repair Versus Replacement for Severe Degenerative Mitral Regurgitation: Analysis of a Large, Prospective, Multicenter, International Registry. Circulation. 2017;135(5):410-22. DOI:10.1161/CIRCULATIONAHA.116.023340.

40. Nishimura RA, O’Gara PT, Bavaria JE, et al. 2019 AATS/ACC/ASE/SCAI/STS expert consensus systems of care document: A proposal to optimize care for patients with valvular heart disease: A Joint Report of the American Association for Thoracic Surgery, American College of Cardiology, American Society of Echocardiography, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Catheter Cardiovasc Interv. 2019;94(1):3-26. DOI:10.1002/ccd.28196.

41. Detaint D, Sundt TM, Nkomo VT, et al. Surgical correction of mitral regurgitation in the elderly: Outcomes and recent improvements. Circulation. 2006;114(4):265- 72. DOI:10.1161/CIRCULATIONAHA.106.619239.

42. DiGregorio V, Zehr KJ, Orszulak TA, et al. Results of mitral surgery in octogenarians with isolated nonrheumatic mitral regurgitation. Ann Thorac Surg. 2004;78(3):807-13. DOI:10.1016/j.athoracsur.2004.03.041.

43. Tribouilloy CM, Enriquez-Sarano M, Schaff HV, et al. Impact of preoperative symptoms on survival after surgical correction of organic mitral regurgitation: Rationale for optimizing surgical indications. Circulation. 1999;99(3):400-5. DOI:10.1161/01.CIR.99.3.400.

44. Enriquez-Sarano M, Tajik AJ, Schaff HV, et al. Echocardiographic prediction of survival after surgical correction of organic mitral regurgitation. Circulation. 1994;90(2):830-7. DOI:10.1161/01.CIR.90.2.830.

45. Tribouilloy CM, Enriquez-Sarano M, Schaff HV, et al. Excess mortality due to coronary artery disease after valve surgery: Secular trends in valvular regurgitation and effect of internal mammary artery bypass. Circulation. 1998;98(19 Suppl): II108-15.

46. Shuhaiber J, Anderson RJ. Meta-analysis of clinical outcomes following surgical mitral valve repair or replacement. Eur J Cardiothorac Surg. 2007;31(2):267-75. DOI:10.1016/j.ejcts.2006.11.014.

47. Acker MA, Parides MK, Perrault LP, et al. Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation. N Engl J Med. 2014;370(1):23-32. DOI:10.1056/NEJMoa1312808.

48. Mihaljevic T, Lam BK, Rajeswaran J, et al. Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation. J Am Coll Cardiol. 2007;49(22):2191-201. DOI:10.1016/j.jacc.2007.02.043.

49. Anantha Narayanan M, Aggarwal S, Reddy YNV, et al. Surgical Repair of Moderate Ischemic Mitral Regurgitation — A Systematic Review and Meta-analysis. Thorac Cardiovasc Surg. 2017;65(5):447-456. DOI:10.1055/s-0036-1598012.

50. Feldman T, Foster E, Glower DD, et al. Percutaneous Repair or Surgery for Mitral Regurgitation. N Engl J Med. 2011;364(15):1395-406. DOI:10.1056/NEJMoa1009355. Erratum in: N Engl J Med. 2011;365(2):189. Glower, Donald G [corrected to Glower, Donald D].

51. Giustino G, Camaj A, Kapadia SR, et al. Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial. J Am Coll Cardiol. 2022;80(20):1857-68. DOI:10.1016/j.jacc.2022.08.803.

52. Obadia JF, Messika-Zeitoun D, Leurent G, et al.; MITRA-FR Investigators. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018;379(24):2297-306. DOI:10.1056/NEJMoa1805374.

53. Anker SD, Friede T, von Bardeleben RS, et al.; RESHAPE-HF2 Investigators. Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation. N Engl J Med. 2024;391(19):1799-809. DOI:10.1056/NEJMoa2314328.

54. Baldus S, Doenst T, Pfister R, et al.; MATTERHORN Investigators. Transcatheter Repair versus Mitral-Valve Surgery for Secondary Mitral Regurgitation. N Engl J Med. 2024;391(19):1787-98. DOI:10.1056/NEJMoa2408739