In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

New analysis from the COAPT trial suggests a broader range of heart failure patients with symptomatic significant functional mitral regurgitation that can benefit from percutaneous edge-to-edge repair.

Original article: Lerakis S et al. Outcomes of transcatheter mitral valve repair for secondary mitral regurgitation by severity of left ventricular dysfunction. EuroIntervention 2021;17:e335-42

Interventional Cardiology
Non-coronary Cardiac Intervention


In the COAPT trial, transcatheter mitral valve edge-to-edge repair improved clinical outcomes in symptomatic patients with heart failure and severe or moderate-to-severe functional mitral regurgitation, refractory to medical therapy. In the latest issue of EuroIntervention, Lerakis et al. published a substudy of the COAPT trial focused on the analysis of outcomes by severity of left ventricular dysfunction. It is important to mention that the original protocol intended to enroll patients with LVFE from 20 to 50% but, in reality, a broader spectrum of patients was recruited (LVEF 12%-65%).

Main results

In this new analysis, the two-year rate of death or heart failure hospitalization was non-significantly different in patients with LVFE ≤40% (n=472) vs. LVFE >40% (n=103) (56.7% vs. 53.4%, HR 1.16, 95% CI: 0.86-1.57, p=0.32). Edge-to-edge repair reduced the two-year rate of death or heart failure hospitalization in both groups (LVFE ≤40% HR 0.50, 95% CI: 0.39-0.65 and LVFE >40% HR 0.60, 95% CI: 0.35-1.05; pint=0.55). Moreover, edge-to-edge repair was consistently effective in reducing the individual endpoints of mortality and heart failure hospitalization, improving mitral regurgitation severity, quality of life, and six-minute walk distance in all subgroups of left ventricular dysfunction (LVFE ≤40%, LVFE >40%, LVEF ≤30% or LVEF >30%).


This new data should be interpreted with caution, considering the inherent limitation of such an analysis using underpowered sub-groups and also the difficulty to assess precisely LVEF in such a population. Nonetheless, these findings clearly suggest that significant symptomatic functional mitral regurgitation is associated with poor prognosis even in patients with preserved LVEF – functional mitral regurgitation is a strong predictor of death even in patients with less severe systolic dysfunction. On the other hand, this paper suggests a similar survival and health status benefit of mitral edge-to-edge repair in a spectrum of left ventricular dysfunction that ranges from preserved to severe. This new hypothesis has the potential to generate new therapeutic opportunities for a large population of patients with poor prognosis.

This analysis raises other important issues. Considering that the degree of LVEF dysfunction is less important for the mitral repair outcome, what other factors are relevant to define prognosis and predict therapeutical benefits? One may be the severity or proportion of mitral regurgitation relative to the degree of LV dysfunction and volume. This may be extrapolated from the comparison of COAPT with MITRA-FR, which included patients with less severe regurgitation (mean effective regurgitant orifice area 0.41 cm2 versus 0.31 cm2) and larger LV end-diastolic volumes. Interestingly, the mean population LVEF was similar in the two studies (31.3% and 33.1%). Different exclusion criteria may also play a determinant role. COAPT excluded patients with evidence of right ventricular dysfunction, severe pulmonary hypertension or severe tricuspid regurgitation.

From the strict aspect of LV function, it is important to stress that patients with significant mitral regurgitation and baseline LVEF of 40%-50% more likely resemble patients with LVEF <40% without mitral regurgitation. Thus, the current analysis does not include patients with truly normal LV function. Further studies are required to examine the outcomes of edge-to-edge repair in such patients, where the underlying mechanism is related with atrial dysfunction.

The paper from Lerakis et al and the editorial comment from Metra & Adamo, in the latest issue of Eurointervention, deserve a careful reading. They point out the limitation of LVEF as a prognostic marker and as a predictor of the beneficial effects of edge-to-edge repair of functional mitral regurgitation. Other factors may play a more determinant role such as LV structure, geometry and dimensions, right ventricular function, pulmonary hypertension, concomitant valve disease, clinical stability and optimal medical treatment. Despite of the inherent limitations of this sub-group analysis, it opens new perspectives and hypothesis regarding the applicability of edge-to-edge repair to broader population.


  • 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;379:2307-18
  • 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. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med 2018;379:2297-306
  • Lerakis S, Kini AS, Asch FM, Kar S, Lim DS, Mishell JM, Whisenant B, Grayburn PA, Weissman NJ, Rinaldi MJ, Sharma SK, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Tang GHL, Li D, Crowley A, Lindenfeld J, Abraham WT, Mack MJ, Stone GW. Outcomes of transcatheter mitral valve repair for secondary mitral regurgitation by severity of left ventricular dysfunction. EuroIntervention 2021;17:e335-42
  • Metra M, Adamo M. Treatment of secondary mitral regurgitation in patients with heart failure: when left ventricular ejection fraction may become not crucial. EuroIntervention 2021;17:e271-e273
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.