Ventricular functional mitral regurgitation: mechanism and therapeutic advances_West China Medical Journal

Authors：

CHEN Panke , HU Xingwei ,  SHI Bei

Department of Cardiology, the Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P. R. China;

Corresponding?author：

SHI Bei, Email: shibei2147@163.com

Keywords：

Mitral regurgitation; ventricular functional mitral regurgitation; transcatheter edge-to-edge repair; heart failure; left ventricular remodeling; treatment strategy

DOI：

10.7507/1002-0179.202509092

Video：

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Abstract Full text Figures/Tables Video References Cited by

Mitral regurgitation is one of the most common valvular heart diseases, with functional mitral regurgitation being the predominant type. Ventricular functional mitral regurgitation (VFMR) occurs due to impaired left ventricular systolic function combined with left ventricular dilation, leading to mitral annular enlargement and papillary muscle displacement, which cause relative tethering of the mitral leaflets despite structurally normal valve apparatus. Patients with VFMR often present with severe heart failure, face high surgical risks, and have a poor prognosis. In recent years, mitral valve transcatheter edge-to-edge repair (TEER) has emerged as a well-established interventional technique, offering a new treatment option for VFMR patients and significantly improving clinical outcomes. This review focuses on the advances in the pathogenesis, epidemiological characteristics, diagnosis, and management of VFMR, particularly the application and efficacy-influencing factors of TEER.

1.	Li RL, Luo CW, Ho YC, et al. Heart valve operations associated with reduced risk of death from mitral valve disease but other operations associated with increased risk of death: a national population-based case-control study. J Cardiothorac Surg, 2019, 14(1): 165.
2.	Hirasawa K, Izumo M. Role of 3D transesophageal echocardiography for transcatheter mitral valve repair-a mini review. Front Cardiovasc Med, 2022, 9: 815304.
3.	Vesely MR, Benitez RM, Robinson SW, et al. Surgical and transcatheter mitral valve repair for severe chronic mitral regurgitation: a review of clinical indications and patient assessment. J Am Heart Assoc, 2015, 4(12): e002424.
4.	Russo E, Russo G, Cassese M, et al. The role of cardiac resynchronization therapy for the management of functional mitral regurgitation. Cells, 2022, 11(15): 2407.
5.	Reid A, Ben Zekry S, Naoum C, et al. Geometric differences of the mitral valve apparatus in atrial and ventricular functional mitral regurgitation. J Cardiovasc Comput Tomogr, 2022, 16(5): 431-441.
6.	Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2021, 143(5): e35-e71.
7.	Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J, 2022, 43(7): 561-632.
8.	Hung JW. Ischemic (functional) mitral regurgitation. Cardiol Clin, 2013, 31(2): 231-236.
9.	Enriquez-Sarano M, Benfari G, Messika-Zeitoun D, et al. Functional mitral regurgitation: a proportionate or disproportionate focus of attention?. Eur J Heart Fail, 2021, 23(10): 1759-1762.
10.	Okamoto C, Okada A, Nishimura K, et al. Prognostic comparison of atrial and ventricular functional mitral regurgitation. Open Heart, 2021, 8(1): e001574.
11.	Claeys MJ, Debonnaire P, Bracke V, et al. Clinical and hemodynamic effects of percutaneous edge-to-edge mitral valve repair in atrial versus ventricular functional mitral regurgitation. Am J Cardiol, 2021, 161: 70-75.
12.	Furukawa A, Abe Y, Ito K, et al. Mechanisms of changes in functional mitral regurgitation by preload alterations. J Cardiol, 2018, 71(6): 570-576.
13.	Carpentier A. Cardiac valve surgery--the “French correction”. J Thorac Cardiovasc Surg, 1983, 86(3): 323-337.
14.	Hirji SA, Cote CL, Javadikasgari H, et al. Atrial functional versus ventricular functional mitral regurgitation: prognostic implications. J Thorac Cardiovasc Surg, 2022, 164(6): 1808-1815.
15.	Dziadzko V, Dziadzko M, Medina-Inojosa JR, et al. Causes and mechanisms of isolated mitral regurgitation in the community: clinical context and outcome. Eur Heart J, 2019, 40(27): 2194-2202.
16.	Gupta R, Gonzales H, Tsai S, et al. Functional mitral regurgitation and the role of transcatheter repair. Struct Heart, 2024, 9(7): 100347.
17.	Stolz L, Doldi PM, Sannino A, et al. The evolving concept of secondary mitral regurgitation phenotypes: lessons from the M-TEER Trials. JACC Cardiovasc Imaging, 2024, 17(6): 659-668.
18.	Tom SK, Kalra K, Perdoncin E, et al. Transcatheter treatment options for functional mitral regurgitation: which device for which patients?. Interv Cardiol, 2024, 19: e10.
19.	Cammalleri V, Antonelli G, De Luca VM, et al. Functional mitral and tricuspid regurgitation across the whole spectrum of left ventricular ejection fraction: recognizing the elephant in the room of heart failure. J Clin Med, 2023, 12(9): 3316.
20.	Sasmita BR, Luo S, Huang B. An updated meta-analysis of treatment in patients with heart failure complicated ventricular functional mitral regurgitation. Rev Cardiovasc Med, 2024, 25(2): 48.
21.	Riccardi M, Cikes M, Adamo M, et al. Functional mitral regurgitation and heart failure with preserved ejection fraction: clinical implications and management. J Card Fail, 2024, 30(7): 929-939.
22.	Mullens W, Martens P. Sacubitril/valsartan to reduce secondary mitral regurgitation. Circulation, 2019, 139(11): 1366-1370.
23.	McGee EC, Gillinov AM, Blackstone EH, et al. Recurrent mitral regurgitation after annuloplasty for functional ischemic mitral regurgitation. J Thorac Cardiovasc Surg, 2004, 128(6): 916-924.
24.	Wakasa S, Shingu Y. Rough-zone suspension with mitral valve replacement for ventricular functional mitral regurgitation. Gen Thorac Cardiovasc Surg, 2024, 72(4): 247-249.
25.	Stone GW, Lindenfeld J, Abraham WT, et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med, 2018, 379(24): 2307-2318.
26.	Obadia JF, Messika-Zeitoun D, Leurent G, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med, 2018, 379(24): 2297-2306.
27.	Izumi Y, Kagiyama N, Maekawara S, et al. Transcatheter edge-to-edge mitral valve repair with extended clip arms for ventricular functional mitral regurgitation. J Cardiol, 2023, 82(4): 240-247.
28.	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): 353-362.
29.	Anker SD, Friede T, von Bardeleben RS, et al. Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials. Eur J Heart Fail, 2024, 26(7): 1608-1615.
30.	Masuda M, Sekiya K, Asai M, et al. Influence of catheter ablation for atrial fibrillation on atrial and ventricular functional mitral regurgitation. ESC Heart Fail, 2022, 9(3): 1901-1913.
31.	Magne J, Lancellotti P, Pierard LA. Exercise pulmonary hypertension in asymptomatic degenerative mitral regurgitation. Circulation, 2010, 122(1): 33-41.
32.	Stocker TJ, Stolz L, Karam N, et al. Long-term outcomes after edge-to-edge repair of secondary mitral regurgitation: 5-year results from the EuroSMR registry. JACC Cardiovasc Interv, 2024, 17(21): 2543-2554.
33.	Stone GW, Abraham WT, Lindenfeld J, et al. Five-year follow-up after transcatheter repair of secondary mitral regurgitation. N Engl J Med, 2023, 388(22): 2037-2048.

1. Li RL, Luo CW, Ho YC, et al. Heart valve operations associated with reduced risk of death from mitral valve disease but other operations associated with increased risk of death: a national population-based case-control study. J Cardiothorac Surg, 2019, 14(1): 165.
2. Hirasawa K, Izumo M. Role of 3D transesophageal echocardiography for transcatheter mitral valve repair-a mini review. Front Cardiovasc Med, 2022, 9: 815304.
3. Vesely MR, Benitez RM, Robinson SW, et al. Surgical and transcatheter mitral valve repair for severe chronic mitral regurgitation: a review of clinical indications and patient assessment. J Am Heart Assoc, 2015, 4(12): e002424.
4. Russo E, Russo G, Cassese M, et al. The role of cardiac resynchronization therapy for the management of functional mitral regurgitation. Cells, 2022, 11(15): 2407.
5. Reid A, Ben Zekry S, Naoum C, et al. Geometric differences of the mitral valve apparatus in atrial and ventricular functional mitral regurgitation. J Cardiovasc Comput Tomogr, 2022, 16(5): 431-441.
6. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2021, 143(5): e35-e71.
7. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J, 2022, 43(7): 561-632.
8. Hung JW. Ischemic (functional) mitral regurgitation. Cardiol Clin, 2013, 31(2): 231-236.
9. Enriquez-Sarano M, Benfari G, Messika-Zeitoun D, et al. Functional mitral regurgitation: a proportionate or disproportionate focus of attention?. Eur J Heart Fail, 2021, 23(10): 1759-1762.
10. Okamoto C, Okada A, Nishimura K, et al. Prognostic comparison of atrial and ventricular functional mitral regurgitation. Open Heart, 2021, 8(1): e001574.
11. Claeys MJ, Debonnaire P, Bracke V, et al. Clinical and hemodynamic effects of percutaneous edge-to-edge mitral valve repair in atrial versus ventricular functional mitral regurgitation. Am J Cardiol, 2021, 161: 70-75.
12. Furukawa A, Abe Y, Ito K, et al. Mechanisms of changes in functional mitral regurgitation by preload alterations. J Cardiol, 2018, 71(6): 570-576.
13. Carpentier A. Cardiac valve surgery--the “French correction”. J Thorac Cardiovasc Surg, 1983, 86(3): 323-337.
14. Hirji SA, Cote CL, Javadikasgari H, et al. Atrial functional versus ventricular functional mitral regurgitation: prognostic implications. J Thorac Cardiovasc Surg, 2022, 164(6): 1808-1815.
15. Dziadzko V, Dziadzko M, Medina-Inojosa JR, et al. Causes and mechanisms of isolated mitral regurgitation in the community: clinical context and outcome. Eur Heart J, 2019, 40(27): 2194-2202.
16. Gupta R, Gonzales H, Tsai S, et al. Functional mitral regurgitation and the role of transcatheter repair. Struct Heart, 2024, 9(7): 100347.
17. Stolz L, Doldi PM, Sannino A, et al. The evolving concept of secondary mitral regurgitation phenotypes: lessons from the M-TEER Trials. JACC Cardiovasc Imaging, 2024, 17(6): 659-668.
18. Tom SK, Kalra K, Perdoncin E, et al. Transcatheter treatment options for functional mitral regurgitation: which device for which patients?. Interv Cardiol, 2024, 19: e10.
19. Cammalleri V, Antonelli G, De Luca VM, et al. Functional mitral and tricuspid regurgitation across the whole spectrum of left ventricular ejection fraction: recognizing the elephant in the room of heart failure. J Clin Med, 2023, 12(9): 3316.
20. Sasmita BR, Luo S, Huang B. An updated meta-analysis of treatment in patients with heart failure complicated ventricular functional mitral regurgitation. Rev Cardiovasc Med, 2024, 25(2): 48.
21. Riccardi M, Cikes M, Adamo M, et al. Functional mitral regurgitation and heart failure with preserved ejection fraction: clinical implications and management. J Card Fail, 2024, 30(7): 929-939.
22. Mullens W, Martens P. Sacubitril/valsartan to reduce secondary mitral regurgitation. Circulation, 2019, 139(11): 1366-1370.
23. McGee EC, Gillinov AM, Blackstone EH, et al. Recurrent mitral regurgitation after annuloplasty for functional ischemic mitral regurgitation. J Thorac Cardiovasc Surg, 2004, 128(6): 916-924.
24. Wakasa S, Shingu Y. Rough-zone suspension with mitral valve replacement for ventricular functional mitral regurgitation. Gen Thorac Cardiovasc Surg, 2024, 72(4): 247-249.
25. Stone GW, Lindenfeld J, Abraham WT, et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med, 2018, 379(24): 2307-2318.
26. Obadia JF, Messika-Zeitoun D, Leurent G, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med, 2018, 379(24): 2297-2306.
27. Izumi Y, Kagiyama N, Maekawara S, et al. Transcatheter edge-to-edge mitral valve repair with extended clip arms for ventricular functional mitral regurgitation. J Cardiol, 2023, 82(4): 240-247.
28. 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): 353-362.
29. Anker SD, Friede T, von Bardeleben RS, et al. Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials. Eur J Heart Fail, 2024, 26(7): 1608-1615.
30. Masuda M, Sekiya K, Asai M, et al. Influence of catheter ablation for atrial fibrillation on atrial and ventricular functional mitral regurgitation. ESC Heart Fail, 2022, 9(3): 1901-1913.
31. Magne J, Lancellotti P, Pierard LA. Exercise pulmonary hypertension in asymptomatic degenerative mitral regurgitation. Circulation, 2010, 122(1): 33-41.
32. Stocker TJ, Stolz L, Karam N, et al. Long-term outcomes after edge-to-edge repair of secondary mitral regurgitation: 5-year results from the EuroSMR registry. JACC Cardiovasc Interv, 2024, 17(21): 2543-2554.
33. Stone GW, Abraham WT, Lindenfeld J, et al. Five-year follow-up after transcatheter repair of secondary mitral regurgitation. N Engl J Med, 2023, 388(22): 2037-2048.

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