Abstract
Functional mitral regurgitation (FMR) occurs when normal or nearly normal mitral leaflets are prevented from proper coaptation by underlying left ventricular (LV) dysfunction, mitral annular dilation, or both. FMR is associated with an adverse prognosis in nonischemic or ischemic LV dysfunction. Multiple studies have confirmed that even mild FMR portends a worse prognosis, and that the risk of FMR is independent of LV volumes and other clinical risk factors. FMR can be difficult to quantitate echocardiographically because it is load dependent and can vary considerably from exam to exam. There is a systematic tendency to underestimate FMR severity by echocardiography because the regurgitant orifice in FMR is typically elliptical, but the formula for calculating regurgitant orifice area assumes circular geometry. Treatment of FMR begins with guideline-directed medical therapy (GDMT) for LV dysfunction and heart failure, including cardiac resynchronization, if indicated. Revascularization should be considered for ischemic FMR, when indicated. Finally, mitral valve surgery should be considered in patients undergoing CABG in whom moderate or greater FMR is present, and also when severe symptomatic FMR persists despite optimal GDMT and revascularization. Percutaneous options for treatment of FMR are in development but are not currently approved in the US.
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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;24:1231–43.
Enriquez-Sarano M, Schaff HV, Orszulak TA, Tajik AJ, Bailey KR, Frye RL. Valve repair improves the outcome of surgery for mitral regurgitation. A multivariate analysis. Circulation. 1995;91:1022–8.
Jokinen JJ, Hippeläinen MJ, Pitkänen OA, Hartikainen JE. Mitral valve replacement vs repair: propensity-adjusted survival and quality-of-life analysis. Ann Thorac Surg. 2007;84:451–8.
David TE, Armstrong S, McCrindle BW, Manlhiot C. Late outcomes of mitral valve repair for mitral regurgitation due to degenerative disease. Circulation. 2013;127:1485–92.
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;91:538–43.
Blondheim DS, Jacobs LE, Kotler MN, Costacurta GA, Parry WR. Dilated cardiomyopathy with mitral regurgitation: decreased survival despite a low frequency of left ventricular thrombus. Am Heart J. 1991;122:763–71.
Robbins JD, Maniar PB, Cotts W, Parker MA, Bonow RO, Gheorghiade M. Prevalence and severity of functional mitral regurgitation in chronic systolic heart failure. Am J Cardiol. 2003;91:360–2.
Patel JB, Borgeson DD, Barnes ME, Rihal CS, Daly RC, Redfield MM. Mitral regurgitation in patients with advanced systolic heart failure. J Card Fail. 2004;10:285–91.
Lamas GA, Mitchell GF, Flaker GC, et al. Clinical significance of mitral regurgitation after acute myocardial infarction. Survival and ventricular enlargement investigators. Circulation. 1997;96:827–33.
Tcheng JE, Jackman Jr JD, Nelson CL, et al. Outcome of patients sustaining acute ischemic mitral regurgitation during myocardial infarction. Ann Intern Med. 1992;117:18–24.
Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103:1759–64.
Grayburn PA, Appleton CP, De Maria AN, Greenberg B, Lowes B, Oh J, et al. BEST Trial Echocardiographic Substudy Investigators. Echocardiographic predictors of morbidity and mortality in patients with advanced heart failure: the Beta-blocker Evaluation of Survival Trial (BEST). J Am Coll Cardiol. 2005;45:1064–71.
Cioffi G, Tarantini L, De Feo S, et al. Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure. Eur J Heart Fail. 2005;7:1112–7.
Rossi A, Dini FL, Faggiano P, Agricola E, et al. Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and non-ischaemic dilated cardiomyopathy. Heart. 2011;97:1675–80.
Deja M, Grayburn P, Sun B, et al. Influence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial. Circulation. 2012;125:2639–48.
Carpentier A. Cardiac valve surgery—the “French correction”. J Thorac Cardiovasc Surg. 1983;86:323–37.
Levine RA, Schwammenthal E. Ischemic mitral regurgitation on the threshold of a solution: from paradoxes to unifying concepts. Circulation. 2005;112:745–58.
Nakai H, Kaku K, Takeuchi M, et al. Different influences of left ventricular remodeling on anterior and posterior mitral leaflet tethering. Circ J. 2012;76:2481–7.
Kwan J, Shiota T, Agler DA, Popovic ZB, Qin JX, Gillinov MA, et al. Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation. Real-time three-dimensional echocardiography study. Circulation. 2003;107:1135–40.
Kaul S, Spotnitz WD, Glasheen WP, Touchstone DA. Mechanism of ischemic mitral regurgitation: an experimental evaluation. Circulation. 1991;84:2167–80.
Meris A, Amigoni M, Verma A, et al. Mechanisms and predictors of mitral regurgitation after high-risk myocardial infarction. J Am Soc Echocardiogr. 2012;25:535–42.
Beaudoin J, Handschumacher MD, Zeng X, Hung J, Morris EL, Levine RA, et al. Mitral valve enlargement in chronic aortic regurgitation as a compensatory mechanism to prevent functional mitral regurgitation in the dilated left ventricle. J Am Coll Cardiol. 2013;61:1809–16.
Chaput M, Handschumacher MD, Tournoux F, et al. Mitral leaflet adaptation to ventricular remodeling: occurrence and adequacy in patients with functional mitral regurgitation. Circulation. 2008;118:845–52.
Grayburn PA. New concepts in functional mitral regurgitation: it is not just a disease of the left ventricle. J Am Coll Cardiol. 2013;61:1817–9.
Gertz ZM, Raina A, Saghy L, et al. Evidence of atrial functional mitral regurgitation due to atrial fibrillation: reversal with arrhythmia control. J Am Coll Cardiol. 2011;58:1474–81.
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;16:777–802.
Lancellottti P, Moura L, Pierard L, et al. European Association of Echocardiography recommendations for the assessment of valvular regurgitation, part 2: mitral and tricuspid regurgitation (native disease). Eur J Echocardiogr. 2010;11:307–32. European Association of Echocardiography Guidelines for assessment of MR.
Grayburn PA, Weissman NJ, Zamorano JL. Quantitation of mitral regurgitation. Circulation. 2012;126:2005–17. Review of imaging methods for quantitation of MR, including 3D echocardiography.
Lancelloti P, Lebrun F, Pierard LA. Determinants of exercise-induced changes in mitral regurgitation in patients with coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol. 2003;42:1921–8.
Mittal AK, Langston Jr M, Cohn KE, Selzer A, Kerth WJ. Combined papillary muscle and left ventricular wall dysfunction as a cause of mitral regurgitation: an experimental study. Circulation. 1971;44:174–80.
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP III, Guyton RA, et al. 2014 AHA/ACC Guidelines for the Management of Patients With Valvular Heart Disease, J Am Coll Cardiol. 2014;[Epub ahead of print]. Updated AHA/ACC guidelines for valvular heart disease.
Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: the Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007;28:230–68.
Dujardin KS, Enriquez-Sarano M, Bailey KR, Nishimura RA, Seward JB, Tajik AJ. Grading of mitral regurgitation by quantitative Doppler echocardiography: calibration by left ventricular angiography in routine clinical practice. Circulation. 1997;96:3409–15.
Smith PK, Michler RE, Woo YJ, et al. Design, rationale, and initiation of the Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial: a report from the Cardiothoracic Surgical Network. J Thorac Cardiovasc Surg. 2012;143:111–7.
Pierard LA, Lancelloti P. The role of ischemic mitral regurgitation in the pathogenesis of acute pulmonary edema. N Engl J Med. 2004;35:1627–34.
Lancellotti P, Troisfontaines P, Toussaint AC, Pierard LA. Prognostic importance of exercise-induced changes in mitral regurgitation in patients with chronic ischemic left ventricular dysfunction. Circulation. 2003;108:875–83.
Hundley WG, Li HF, Willard JE, et al. Magnetic resonance imaging assessment of the severity of mitral regurgitation: comparison with invasive techniques. Circulation. 1995;92:1151–8.
Gelfand EV, Hughes S, Hauser TH, et al. Severity of mitral and aortic regurgitation as assessed by cardiovascular magnetic resonance: optimizing correlation with Doppler echocardiography. J Cardiovasc Magn Reson. 2006;8:503–7.
Van de Heyning CM, Magne J, Vrints CJ, Piérard L, Lancellotti P. The role of multi-imaging modality in primary mitral regurgitation. Eur Heart J Cardiovasc Imaging. 2012;13:139–51.
Schiros CG, Dell'italia LJ, Gladden JD, et al. Magnetic resonance imaging with 3-dimensional analysis of left ventricular remodeling in isolated mitral regurgitation: implications beyond dimensions. Circulation. 2012;125:2334–42.
Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147–239. Updated AHA/ACC guidelines for heart failure.
McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–69.
Comin-Colet J, Sánchez-Corral MA, Manito N, et al. Effect of carvedilol therapy on functional mitral regurgitation, ventricular remodeling, and contractility in patients with heart failure due to left ventricular systolic dysfunction. Transplant Proc. 2002;34:177–8.
Kanzaki H, Bazaz R, Schwartzman D, et al. A mechanism for immediate reduction in mitral regurgitation after cardiac resynchronization therapy. J Am Coll Cardiol. 2004;44:1619–25.
Porciani MC, Macioce R, Demarchi G, et al. Effects of cardiac resynchronization therapy on the mechanisms underlying functional mitral regurgitation in congestive heart failure. Eur J Echocardiogr. 2006;7:31–9.
Goland S, Rafique AM, Mirocha J, Siegel RJ, Naqvi TZ. Reduction in mitral regurgitation in patients undergoing cardiac resynchronization treatment: assessment of predictors by two-dimensional radial strain echocardiography. Echocardiography. 2009;26:420–30.
Brandt RR, Reiner C, Arnold R, Sperzel J, Pitschner HF, Hamm CW. Contractile response and mitral regurgitation after temporary interruption of long-term cardiac resynchronization therapy. Eur Heart J. 2006;27:187–92.
Kuppahally SS, Fowler MB, Vagelos R, Wang P, Al-Ahmad A, Paloma A, et al. Worsening of left ventricular end-systolic volume and mitral regurgitation without increase in left ventricular dyssynchrony on acute interruption of cardiac resynchronization therapy. Echocardiography. 2009;26:759–65.
Cazeau S, Leclercq C, Lavergne T, et al. Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators. Effect of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001;344:873–80.
Abraham WT, Fisher WG, Smith AL, et al. Multicenter InSync randomized clinical evaluation. Cardiac resynchronization therapy in chronic heart failure. N Engl J Med. 2002;346:1845–53.
Sutton MG, Plappert T, Hilpisch KE, Abraham WT, Hayes DL, Chinchoy E. Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Circulation. 2006;113:266–72.
Di Biase L, Auricchio A, Mohanty P, et al. Impact of cardiac resynchronization therapy on the severity of mitral regurgitation. Europace. 2011;13:829–38.
Onishi T, Onishi T, Marek JJ, et al. Mechanistic features associated with improvement in mitral regurgitation after cardiac resynchronization therapy and their relation to long-term patient outcome. Circ Heart Fail. 2013;6:685–93.
Van Bommel RJ, Marsan NA, Delgado V, et al. Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation. 2011;124:912–9.
Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364:1607–16. Randomized trial of GDMT vs CABG + GDMT in ischemic heart failure.
Kang DH, Sun BJ, Kim DH, et al. Percutaneous vs surgical revascularization in patients with ischemic mitral regurgitation. Circulation. 2011;124(11 Suppl):S156–62.
Prifti E, Bonacchi M, Frati G, et al. Should mild-to-moderate and moderate ischemic mitral regurgitation be corrected in patients with impaired left ventricular function undergoing simultaneous coronary revascularization? J Card Surg. 2001;16:473–83.
Harris KM, Sundt III TM, Aeppli D, Sharma R, Barzilai B. Can late survival of patients with moderate ischemic mitral regurgitation be impacted by intervention on the valve? Ann Thorac Surg. 2002;74:1468–75.
Balu V, Hershowitz S, Zaki Masud A, et al. Mitral regurgitation in coronary artery disease. Chest. 1982;81:550–5.
Grossi EA, Zakow PK, Sussman M, et al. Late results of mitral valve reconstruction in the elderly. Ann Thorac Surg. 2000;70:1224–6.
Fattouch K, Guccione F, Sampognaro R, Panzarella G, Corrado E, Navarra E, et al. Point: efficacy of adding mitral valve restrictive annuloplasty to coronary artery bypass grafting in patients with moderate ischemic mitral valve regurgitation: a randomized trial. J Thorac Cardiovasc Surg. 2009;138:278–85.
Chan KM, Punjabi PP, Flather M, Wage R, Symmonds K, Roussin I, et al. Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation: final results of the Randomized Ischemic Mitral Evaluation (RIME) trial. Circulation. 2012;126:2502–10.
Wu A, Aaronson K, Bolling S, et al. Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol. 2005;45:381–7.
Acker MA, Bolling S, Shemin R, et al. Mitral valve surgery in heart failure: insights from the Acorn Clinical Trial. J Thorac Cardiovasc Surg. 2006;132:568–77.
Braun J, Bax JJ, Versteegh MI, Voigt PG, Holman ER, Klautz RJ, et al. Preoperative left ventricular dimensions predict reverse remodeling following restrictive mitral annuloplasty in ischemic mitral regurgitation. Eur J Cardiothorac Surg. 2005;27:847–53.
Gillinov A, Wierup P, Blackstone E, et al. Is repair preferable to replacement for ischemic mitral regurgitation? J Thorac Cardiovasc Surg. 2001;122:1125–41.
Mihaljevic T, Lam B, Rajeswaran J, et al. Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation. J Am Coll Cardiol. 2007;49:2191–201.
Ryan L, Jackson B, Hamamoto H, et al. The influence of annuloplasty ring geometry on mitral leaflet curvature. Ann Thorac Surg. 2008;86:749–60.
Acker M. Should moderate or greater mitral regurgitation be repaired in all patients with LVEF <30 %? Mitral valve repair in patients with advanced heart failure and severe functional mitral insufficiency reverses left ventricular remodeling and improves symptoms. Circ Heart Fail. 2008;1:281–4.
Braun J, van de Veire NR, Klautz RJ, et al. Restrictive mitral annuloplasty cures ischemic mitral regurgitation and heart failure. Ann Thorac Surg. 2008;85:430–6.
Jimenez J, Liou S, Padala M, et al. A saddle-shaped annulus reduces systolic strain on the central region of the mitral valve anterior leaflet. J Thorac Cardiovasc Surg. 2007;134:1562–8.
Kron I, Green G, Cope J. Surgical relocation of the posterior papillary muscle in chronic ischemic mitral regurgitation. Ann Thorac Surg. 2002;74:600–1.
David TE, Uden DE, Strauss HD. The importance of the mitral apparatus in left ventricular function after correction of mitral regurgitation. Circulation. 1983;68:1176–82.
David TE, Burns RJ, Bacchus CM, Druck MN. Mitral valve replacement for mitral regurgitation with and without preservation of chordae tendineae. J Thorac Cardiovasc Surg. 1984;88:718–25.
Rozich JD, Carabello BA, Usher BW, Kratz JM, Bell AE, Zile MR. Mitral valve replacement with and without chordal preservation in patients with chronic mitral regurgitation. Mechanisms for differences in postoperative ejection performance. Circulation. 1992;86:1718–26.
Horskotte D, Schulte HD, Bircks W, Strauer BE. The effect of chordal preservation on late outcome after mitral valve replacement: a randomized study. J Heart Valve Dis. 1993;2:150–8.
Khabbaz KR, Mahmood F, Shakil O, et al. Dynamic 3-dimensional echocardiographic assessment of mitral annular geometry in patients with functional mitral regurgitation. Ann Thorac Surg. 2013;95:105–10.
Gillinov AM, Wierup PN, Blackstone EH, et al. Is repair preferable to replacement for ischemic mitral regurgitation? J Thorac Cardiovasc Surg. 2001;122:1125–241.
Filsoufi F, Salzberg S, Adams D. Current management of ischemic mitral regurgitation. Mt Sinai J Med. 2005;72:105–15.
Adams D, Filsoufi F, Aklog L. Surgical treatment of the ischemic mitral valve. J Heart Valve Dis. 2002;11:S21–5.
Acker MA, Parides MK, Perrault LP, Moskowitz AJ, et al. Mitral-valve repair vs replacement for severe ischemic mitral regurgitation. N Engl J Med. 2014;370:23–32. Randomized trial of mitral valve replacement vs repair in ischemic FMR.
Feldman T, Young A. Percutaneous approaches to valve repair in mitral regurgitation. J Am Coll Cardiol. 2014; [Epub ahead of print].
Feldman T, Foster E, Glower D, Kar S, Rinaldi MJ, Fail PS, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011;364:1395–406.
Mauri L, Foster E, Glower DD, Apruzzese P, Massaro JM, Herrmann HC, et al. Four-year results of a randomized controlled trial of percutaneous repair vs surgery for mitral regurgitation. J Am Coll Cardiol. 2013;62:317–28.
Foster E, Kwan D, Feldman T, Weissman N, Grayburn P, Schwartz A, et al. Percutaneous mitral valve repair in the initial EVEREST cohort: evidence of reverse left ventricular remodeling. Circ Cardiovasc Interv. 2013;6:522–30.
Grayburn PA, Sangli C, Massaro J, Mauri L, Weissman NJ, Glower DG, et al. The relationship between the magnitude of reduction in mitral regurgitation severity and left ventricular and left atrial reverse remodeling after MitraClip therapy. Circulation. 2013;128:1667–74.
Auricchio A, Schillinger W, Meyer S, Maisano F, Hoffmann R, Ussia GP, et al. PERMIT-CARE Investigators. Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling. J Am Coll Cardiol. 2011;58:2183–9.
Glower DD, Kar S, Trento A, Lim DS, Bajwa T, Quesada R, et al. Percutaneous MitraClip® device therapy for mitral regurgitation in 351 patients: high risk subset of the EVEREST II Study. J Am Coll Cardiol. 2013; [In press].
Siminiak T, Wu JC, Haude M, Hoppe UC, Sadowski J, Lipiecki J, et al. Treatment of functional mitral regurgitation by percutaneous annuloplasty: results of the TITAN Trial. Eur J Heart Fail. 2012;14:931–8.
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Mina M. Benjamin declares that he has no conflict of interest. Robert L. Smith declares that he has no conflict of interest. Paul A. Grayburn reports grants and personal fees from Abbott Vascular, grants from Medtronic, grants from Edwards, grants from Aastrom, grants from Guided Delivery Systems, and grants from Valtech Cardio.
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Benjamin, M.M., Smith, R.L. & Grayburn, P.A. Ischemic and Functional Mitral Regurgitation in Heart Failure: Natural History and Treatment. Curr Cardiol Rep 16, 517 (2014). https://doi.org/10.1007/s11886-014-0517-0
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DOI: https://doi.org/10.1007/s11886-014-0517-0