Functional mitral regurgitation (FMR)

Functional mitral regurgitation (FMR)

Functional mitral regurgitation (FMR) occurs due to non-coaptation of mitral leaflets in the setting of left ventricular dilatation. It can occur in cardiomyopathies of both ischemic and idiopathic varieties as well as in left ventricular dilatation due to aortic regurgitation. The distorted shape of the left ventricles restricts the mitral valve closure. Left ventricular remodeling is largely responsible for functional mitral regurgitation. There is increased sphericity of the left ventricle with longer tethering distance and enlarged mitral annulus. But the incidence of functional mitral regurgitation is less than what is expected from left ventricular remodeling. This is thought to be due to the enlargement of mitral leaflets in response to left ventricular enlargement and change in morphology. Enlargement of mitral leaflets may not be due to stretch alone, but also due to active growth of cells and matrix. The enlargement of mitral leaflets causing a less than expected rate of functional mitral regurgitation is more likely to occur in slowly progressive left ventricular dilatation as in chronic aortic regurgitation. For this reason, the chance of functional mitral regurgitation is less in chronic aortic regurgitation than in other cases with corresponding severity of left ventricular dilatation [1].

Proportionate and disproportionate functional MR

Going by the Gorlin hydraulic orifice equation, patients with left ventricular ejection fraction of 30% and a left ventricular end diastolic volume (LVEDV) of 220-250 ml and regurgitant fraction of 50% is expected to have an effective regurgitant orifice area (EROA) of 0.3 cm². MR in these patients is proportionate to the degree of left ventricular dilatation, independent of specific tethering abnormalities of mitral valve leaflets, and can respond to drugs and devices that reduce LVEDV [2]. Patients with EROA of 0.3 – 0.4 cm², but with LVEDV of only 160-200 ml have MR disproportionately higher than predicted by the LVEDV. These patients may be preferentially benefitted from interventions directed at the mitral valve.

MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial enrolled patients with proportionate MR. Mean LVEDV was 252 ml and the mean EROA was 31 mm² in this study. Clinical outcomes of these patients did not differ from medically treated control patients at both one year and two year follow up [3,4].

COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial had chronic heart failure patients with reduced left ventricular ejection fraction and severe secondary MR [5]. Trans catheter mitral valve repair resulted in lower rate of hospitalization for heart failure and lower all cause mortality at 2 years than medical therapy alone. Freedom from device related complications was 96.6% at 12 months. There was a significant reduction of left ventricular volumes at 1 year. Mean LVEDV was 192 ml and mean EROA was 41 mm² indicating disproportionate MR. It has been suggested that the difference in outcome between MITRA-FR and COPAT trials could have been due to the difference in proportionate vs disproportionate functional MR [2].

References

1. Beaudoin J, Handschumacher MD, Zeng X, Hung J, Morris EL, Levine RA, Schwammenthal E. 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;61:1809-1809.
2. 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 Feb;12(2):353-362.
3. Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, Lefèvre T, Piot C, Rouleau F, Carrié D, Nejjari M, Ohlmann P, Leclercq F, Saint Etienne C, Teiger E, Leroux L, Karam N, Michel N, Gilard M, Donal E, Trochu JN, Cormier B, Armoiry X, Boutitie F, Maucort-Boulch D, Barnel C, Samson G, Guerin P, Vahanian A, Mewton N; MITRA-FR Investigators. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018 Dec 13;379(24):2297-2306.
4. Iung B, Armoiry X, Vahanian A, Boutitie F, Mewton N, Trochu JN, Lefèvre T, Messika-Zeitoun D, Guerin P, Cormier B, Brochet E, Thibault H, Himbert D, Thivolet S, Leurent G, Bonnet G, Donal E, Piriou N, Piot C, Habib G, Rouleau F, Carrié D, Nejjari M, Ohlmann P, Saint Etienne C, Leroux L, Gilard M, Samson G, Rioufol G, Maucort-Boulch D, Obadia JF; MITRA-FR Investigators. Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years. Eur J Heart Fail. 2019 Dec;21(12):1619-1627.
5. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant B, Grayburn PA, Rinaldi M, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Marx SO, Cohen DJ, Weissman NJ, Mack MJ; COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318.