Treatment of functional mitral regurgitation in chronic heart failure: can we get a 'proof of concept' from the MITRA-FR and COAPT trials?

Functional mitral regurgitation (FMR) is associated with poor outcomes in patients with heart failure (HF). However, it is not clear whether FMR is just a consequence of left ventricular (LV) remodelling or a factor contributing to cardiomyopathy progression. There will be more clarity about this controversy when the effects of FMR correction on outcomes will be shown. FMR correction can be performed surgically or, more often, percutaneously with the MitraClip procedure. MitraClip is the most widely used device with more than 70 000 implants performed to date. Observational studies suggest that MitraClip treatment of FMR is safe and associated with improved symptoms, quality of life and functional status in HF patients. Two recently randomized controlled clinical trials have investigated the impact of MitraClip on the outcomes of HF patients: Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) and Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT). Both trials randomized patients to MitraClip plus guideline-directed medical therapy (GDMT) or GDMT alone. No reduction in the primary endpoint of all-cause mortality or HF hospitalizations was shown in MITRA-FR, whereas a significant reduction in HF hospitalizations (primary endpoint) as well as in mortality alone were shown in COAPT. The aim of this review is to summarize the pathophysiology, prevalence, prognostic role and management of FMR, focusing on the differences between MITRA-FR and COAPT and trying to provide possible explanations for the diverging results. We speculate that the two trials should be interpreted as complementary rather than opposite. Patients with severe FMR (effective regurgitant orifice area > 30 mm2 ) despite maximum tolerated GDMT (including cardiac resynchronization therapy), and without too advanced cardiomyopathy seem to be the best candidates for MitraClip treatment. MITRA-FR and COAPT provide us a long awaited 'proof of concept': FMR may be considered a leading actor in cardiomyopathy progression rather than a mere marker of severity.