Current Cardiology Reports

, 21:139 | Cite as

Treatment of Functional Mitral Regurgitation in Heart Failure

  • Enrico FabrisEmail author
  • Antonio De Luca
  • Giancarlo Vitrella
  • Davide Stolfo
  • Marco Masè
  • Renata Korcova
  • Marco Merlo
  • Serena Rakar
  • Arnoud W. J. van’t Hof
  • Elvin Kedhi
  • Andrea Perkan
  • Gianfranco Sinagra
Myocardial Disease (A Abbate and G Sinagra, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Myocardial Disease


Purpose of Review

To analyze the current state of the art of functional mitral regurgitation (FMR) treatment.

Recent Findings

The first-line treatment of severe FMR consists of guideline medical therapy (GMT) and resynchronization therapy when indicated; the impact of new medical therapies like sacubitril/valsartan needs further assessment. Valvular intervention may be considered in FMR symptomatic patients despite GMT, and can be performed surgically or percutaneously. MitraClip is a safe percutaneous procedure associated with symptoms improvement. Recently, the COAPT trial showed superior outcomes for MitraClip versus GMT contrasting the MITRA-FR trial which showed no benefit of MitraClip compared with GMT. These results should be interpreted as complementary rather than opposite.


The COAPT trial provided a “proof of concept” that percutaneous treatment of severe FMR in patients without too advanced left ventricular disease translates into a prognostic benefit. Careful patient selection will play a critical role in defining the clinical niche for successful interventions.


Functional mitral regurgitation Mitral valve repair Transcatheter interventions MitraClip Heart failure Heart team 


Compliance with Ethical Standards

Conflict of Interest

Enrico Fabris, Antonio De Luca, Giancarlo Vitrella, Davide Stolfo, Marco Masè, Renata Korcova, Marco Merlo, Serena Rakar, Elvin Kedhi and Andrea Perkan declare that they have no conflict of interest.

Arnoud WJ van’t Hof reports grants from Medtronic and Abbott, and personal fees from AstraZeneca.

Gianfranco Sinagra reports personal fees from Novartis, Vifor pharma, Boston, Bayer, AstraZeneca, and Dompè.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Baumgartner H, Falk V, Bax JJ, de Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2017;38(36):2739–91. Scholar
  2. 2.
    Rossi A, Dini FL, Faggiano P, Agricola E, Cicoira M, Frattini S, 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(20):1675–80. Scholar
  3. 3.
    Varadarajan P, Sharma S, Heywood JT, Pai RG. High prevalence of clinically silent severe mitral regurgitation in patients with heart failure: role for echocardiography. J Am Soc Echocardiogr. 2006;19(12):1458–61. Scholar
  4. 4.
    Sannino A, Smith RL, Schiattarella GG, Trimarco B, Esposito G, Grayburn PA. Survival and cardiovascular outcomes of patients with secondary mitral regurgitation. JAMA Cardiol. 2017;2(10):1130–9. Scholar
  5. 5.
    Goliasch G, Bartko PE, Pavo N, Neuhold S, Wurm R, Mascherbauer J, et al. Refining the prognostic impact of functional mitral regurgitation in chronic heart failure. Eur Heart J. 2018;39(1):39–46. Scholar
  6. 6.
    Inciardi RM, Rossi A, Benfari G, Cicoira M. Fill in the gaps of secondary mitral regurgitation: a continuum challenge from pathophysiology to prognosis. Curr Heart Fail Rep. 2018;15(2):106–15. Scholar
  7. 7.
    Nappi F, Avatar Singh SS, Santana O, Mihos CG. Functional mitral regurgitation: an overview for surgical management framework. J Thorac Dis. 2018;10(7):4540–55. Scholar
  8. 8.
    Piérard LA, Carabello BA. Ischaemic mitral regurgitation: pathophysiology, outcomes and the conundrum of treatment. Eur Heart J. 2010;31(24):2996–3005. Scholar
  9. 9.
    Liang JJ, Silvestry FE. Mechanistic insights into mitral regurgitation due to atrial fibrillation: “atrial functional mitral regurgitation”. Trends Cardiovasc Med. 2016;26(8):681–9. Scholar
  10. 10.
    Mark JB, Chetham PM. Ventricular pacing can induce hemodynamically significant mitral valve regurgitation. Anesthesiology. 1991;74(2):375–7 Accessed May 19, 2019.CrossRefGoogle Scholar
  11. 11.
    Wong DTL, Leong DP, Khurana S, Puri R, Tayeb H, Sanders P. Severe mitral regurgitation due to right ventricular apical pacing. Case Reports. 2010;2010(oct29 1):bcr1220092524. Scholar
  12. 12.
    Sherrid MV, Balaram S, Kim B, Axel L, Swistel DG. The mitral valve in obstructive hypertrophic cardiomyopathy: a test in context. J Am Coll Cardiol. 2016;67(15):1846–58. Scholar
  13. 13.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1–39.e14. Scholar
  14. 14.
    Wunderlich NC, Beigel R, Ho SY, Nietlispach F, Cheng R, Agricola E, et al. Imaging for mitral interventions: methods and efficacy. JACC Cardiovasc Imaging. 2018;11(6):872–901. Scholar
  15. 15.
    Lancellotti P, Tribouilloy C, Hagendorff A, Popescu BA, Edvardsen T, Pierard LA, et al. Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2013;14(7):611–44. Scholar
  16. 16.
    Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, et al. Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2017;30(4):303–71. Scholar
  17. 17.
    Goebel B, Heck R, Hamadanchi A, Otto S, Doenst T, Jung C, et al. Vena contracta area for severity grading in functional and degenerative mitral regurgitation: a transoesophageal 3D colour Doppler analysis in 500 patients. Eur Heart J Cardiovasc Imaging. 2018;19(6):639–46. Scholar
  18. 18.
    • Bartko PE, Arfsten H, Heitzinger G, Pavo N, Toma A, Strunk G, et al. A unifying concept for the quantitative assessment of secondary mitral regurgitation. J Am Coll Cardiol. 2019;73(20):2506–17. This article provides further insights regarding the evaluation of the severity of mitral regurgitation.CrossRefPubMedGoogle Scholar
  19. 19.
    • Grayburn PA, Sannino A, Packer M. Proportionate and disproportionate functional mitral regurgitation: a new conceptual framework that reconciles the results of the MITRA-FR and COAPT trials. JACC Cardiovasc Imaging. 2019;12(2):353–62. This article introduces the concept of proportionate and disproportionate functional mitral regurgitation.CrossRefGoogle Scholar
  20. 20.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37(27):2129–200. Scholar
  21. 21.
    St John Sutton MG, Plappert T, Abraham WT, Smith AL, DeLurgio DB, Leon AR, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation. 2003;107(15):1985–90. Scholar
  22. 22.
    Kang D-H, Park S-J, Shin S-H, Hong GR, Lee S, Kim MS, et al. Angiotensin receptor neprilysin inhibitor for functional mitral regurgitation. Circulation. 2019;139(11):1354–65. Scholar
  23. 23.
    van Bommel RJ, Marsan NA, Delgado V, Borleffs CJW, van Rijnsoever EPM, Schalij MJ, et al. Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation. 2011;124(8):912–9. Scholar
  24. 24.
    Cipriani M, Lunati M, Landolina M, Proclemer A, Boriani G, Ricci RP, et al. Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy. Eur J Heart Fail. 2016;18(8):1060–8. Scholar
  25. 25.
    Onishi T, Onishi T, Marek JJ, Ahmed M, Haberman SC, Oyenuga O, 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(4):685–93. Scholar
  26. 26.
    Stolfo D, Tonet E, Barbati G, et al. Acute hemodynamic response to cardiac resynchronization in dilated cardiomyopathy: effect on late mitral regurgitation. Pacing Clin Electrophysiol. 2015;38(11):1287–96. Scholar
  27. 27.
    Wu AH, Aaronson KD, Bolling SF, Pagani FD, Welch K, Koelling TM. Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol. 2005;45(3):381–7. Scholar
  28. 28.
    Mihaljevic T, Lam B-K, Rajeswaran J, Takagaki M, Lauer MS, Gillinov AM, 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. Scholar
  29. 29.
    Panaich SS, Arora S, Badheka A, Kumar V, Maor E, Raphael C, et al. Procedural trends, outcomes, and readmission rates pre-and post-FDA approval for MitraClip from the National Readmission Database (2013-14). Catheter Cardiovasc Interv. 2018;91(6):1171–81. Scholar
  30. 30.
    Mauri L, Foster E, Glower DD, Apruzzese P, Massaro JM, Herrmann HC, et al. 4-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J Am Coll Cardiol. 2013;62(4):317–28. Scholar
  31. 31.
    Maisano F, Franzen O, Baldus S, Schäfer U, Hausleiter J, Butter C, et al. Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe. J Am Coll Cardiol. 2013;62(12):1052–61. Scholar
  32. 32.
    •• Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018;379(24):2307–18. This is an important large randomized trial that showed superior outcomes for Mitraclip compared with medical therapy in patients with functional mitral regurgitation.CrossRefGoogle Scholar
  33. 33.
    Barbanti M, Immè S, Grasso C. Transcatheter mitral valve repair: a brief review. EuroIntervention. 2015;11(Suppl W(W)):W42–4. Scholar
  34. 34.
    Nickenig G, Estevez-Loureiro R, Franzen O, Tamburino C, Vanderheyden M, Lüscher TF, et al. Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 pilot European Sentinel Registry. J Am Coll Cardiol. 2014;64(9):875–84. Scholar
  35. 35.
    Capodanno D, Adamo M, Barbanti M, Giannini C, Laudisa ML, Cannata S, et al. Predictors of clinical outcomes after edge-to-edge percutaneous mitral valve repair. Am Heart J. 2015;170(1):187–95. Scholar
  36. 36.
    Puls M, Lubos E, Boekstegers P, von Bardeleben RS, Ouarrak T, Butter C, et al. One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry. Eur Heart J. 2016;37(8):703–12. Scholar
  37. 37.
    Feldman T, Foster E, Glower D, Kar S. Percutaneous repair or surgery for mitral regurgitation. New Engl J Med. 2011;364(15):2187–98. Scholar
  38. 38.
    •• Obadia J-F, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med. 2018;379(24):2297–306. The first large randomized trial comparing MitraClip treatment versus medical therapy in patients with functional mitral regurgitation.CrossRefGoogle Scholar
  39. 39.
    Batchelor W, Starling RC, Stone GW. Secondary mitral regurgitation: is it time for a paradigm shift in treatment? JACC Heart Fail. 2019;7(6):522–6. Scholar
  40. 40.
    Packer M, Grayburn PA. Contrasting effects of pharmacological, procedural and surgical interventions on proportionate and disproportionate functional mitral regurgitation in chronic heart failure. Circulation. 2019;CIRCULATIONAHA.119.039612. Scholar
  41. 41.
    Senni M, Adamo M, Metra M, Alfieri O, Vahanian A. Treatment of functional mitral regurgitation in chronic heart failure: can we get a “proof of concept” from the MITRA-FR and COAPT trials? Eur J Heart Fail. 2019;2019:ejhf.1491. Scholar
  42. 42.
    Whitlow PL, Feldman T, Pedersen WR, Lim DS, Kipperman R, Smalling R, et al. Acute and 12-month results with catheter-based mitral valve leaflet repair: the EVEREST II (endovascular valve edge-to-edge repair) high risk study. J Am Coll Cardiol. 2012;59(2):130–9. Scholar
  43. 43.
    Sürder D, Pedrazzini G, Gaemperli O, Biaggi P, Felix C, Rufibach K, et al. Predictors for efficacy of percutaneous mitral valve repair using the MitraClip system: the results of the MitraSwiss registry. Heart. 2013;99(14):1034–40. Scholar
  44. 44.
    Stolfo D, De Luca A, Morea G, et al. Predicting device failure after percutaneous repair of functional mitral regurgitation in advanced heart failure: implications for patient selection. Int J Cardiol. 2018;257:182–7. Scholar
  45. 45.
    Taramasso M, Denti P, Latib A, Guidotti A, Buzzatti N, Pozzoli A, et al. Clinical and anatomical predictors of MitraClip therapy failure for functional mitral regurgitation: single central clip strategy in asymmetric tethering. Int J Cardiol. 2015;186:286–8. Scholar
  46. 46.
    De Luca A, Stolfo D, Korcova R, et al. Prognostic value of global longitudinal strain-based left ventricular contractile reserve in candidates for percutaneous correction of functional mitral regurgitation: implications for patient selection. J Am Soc Echocardiogr. in press.Google Scholar
  47. 47.
    Merlo M, Pyxaras SA, Pinamonti B, Barbati G, Di Lenarda A, Sinagra G. Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. J Am Coll Cardiol. 2011;57(13):1468–76. Scholar
  48. 48.
    Pleger ST, Schulz-Schönhagen M, Geis N, Mereles D, Chorianopoulos E, Antaredja M, et al. One year clinical efficacy and reverse cardiac remodelling in patients with severe mitral regurgitation and reduced ejection fraction after MitraClip implantation. Eur J Heart Fail. 2013;15(8):919–27. Scholar
  49. 49.
    Taramasso M, Maisano F, Latib A, Denti P, Buzzatti N, Cioni M, et al. Clinical outcomes of MitraClip for the treatment of functional mitral regurgitation. EuroIntervention. 2014;10(6):746–52. Scholar
  50. 50.
    Berardini A, Biagini E, Saia F, Stolfo D, Previtali M, Grigioni F, et al. Percutaneous mitral valve repair: the last chance for symptoms improvement in advanced refractory chronic heart failure? Int J Cardiol. 2017;228:191–7. Scholar
  51. 51.
    Grayburn PA, Foster E, Sangli C, Weissman NJ, Massaro J, Glower DG, et al. Relationship between the magnitude of reduction in mitral regurgitation severity and left ventricular and left atrial reverse remodeling after MitraClip therapy. Circulation. 2013;128(15):1667–74. Scholar
  52. 52.
    Adamo M, Godino C, Giannini C, Scotti A, Liga R, Curello S, et al. Left ventricular reverse remodelling predicts long-term outcomes in patients with functional mitral regurgitation undergoing MitraClip therapy: results from a multicentre registry. Eur J Heart Fail. 2019;21(2):196–204. Scholar
  53. 53.
    Bail DHL. Treatment of functional mitral regurgitation by percutaneous annuloplasty using the Carillon Mitral Contour System-currently available data state. J Interv Cardiol. 2017;30(2):156–62. Scholar
  54. 54.
    Nickenig G, Schueler R, Dager A, Martinez Clark P, Abizaid A, Siminiak T, et al. Treatment of chronic functional mitral valve regurgitation with a percutaneous annuloplasty system. J Am Coll Cardiol. 2016;67(25):2927–36. Scholar
  55. 55.
    Seferovic PM, Ponikowski P, Anker SD, et al. Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019;2019:ejhf.1531. Scholar
  56. 56.
    Sinagra G, Fabris E, Tavazzi L. The evolution of cardiology: changes, future challenges and opportunities. Futur Cardiol. 2017;13(2):161–71. Scholar
  57. 57.
    Chambers JB, Lloyd G, Rimington HM, et al. The case for a specialist multidisciplinary valve clinic. J Heart Valve Dis. 2012;21(1):1–4 Accessed July 5, 2019.PubMedGoogle Scholar
  58. 58.
    Holmes DR, Rich JB, Zoghbi WA, Mack MJ. The heart team of cardiovascular care. J Am Coll Cardiol. 2013;61(9):903–7. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Enrico Fabris
    • 1
    Email author
  • Antonio De Luca
    • 1
  • Giancarlo Vitrella
    • 1
  • Davide Stolfo
    • 1
  • Marco Masè
    • 1
  • Renata Korcova
    • 1
  • Marco Merlo
    • 1
  • Serena Rakar
    • 1
  • Arnoud W. J. van’t Hof
    • 2
    • 3
  • Elvin Kedhi
    • 4
  • Andrea Perkan
    • 1
  • Gianfranco Sinagra
    • 1
  1. 1.Cardiovascular DepartmentUniversity of TriesteTriesteItaly
  2. 2.Department of CardiologyMaastricht University Medical CenterMaastrichtthe Netherlands
  3. 3.Department of CardiologyZuyderland Medical CenterHeerlenthe Netherlands
  4. 4.AZ Sint-Jan BruggeBrugesBelgium

Personalised recommendations