Futile MITRA-FR and a positive COAPT trial: Where does the evidence leave the clinicians?

Secondary mitral regurgitation (MR) in dilated ventricles is a cardiovascular disease condition that has an enormous population burden and significantly contributes to the high mortality in heart failure with reduced ejection fraction (HFrEF) patients.Moreover, cardiovascular physicians and scientists have been struggling to find a therapeutic answer for secondary MR in HFrEF patients over the last few decades.Previous randomized controlled trials (RCTs) looking for an annular surgical solution (e.g., an undersized annuloplasty ring) to a ventricular problem (i.e., left ventricular dysfunction causing annular dilatation and secondary MR) have been largely negative [1].Recently, the results of the COAPT trial [2] comparing a percutaneous mitral-valve repair therapy (using a MitraClip device) plus medical therapy to medical therapy alone in carefully selected HFrEF patients with more than moderate secondary MR were published.The absolute risk reduction in all-cause mortality in patients receiving the MitraClip in the COAPT trial [2] was 17% which translated to a number needed to treat (NNT) of 6 to prevent one death over two years, similar NNT was observed with the use of renin-angiotensin inhibitors in HFrEF.Not only that, the results showed similarly impressive reductions in all-cause mortality across the various pre-specified subgroup analyses in the COAPT trial [2].Success and effect size of this magnitude does not happen frequently, and this certainly should be considered as welcoming news to the clinicians and patients alike.But a key question to consider is that if an effect size like this is biologically plausible?Especially when our percutaneous approach of treatment using the MitraClip device is fundamentally similar to what our surgical colleagues have done with an annuloplasty ring over the last few decades.In both the percutaneous