Clip therapy for secondary mitral regurgitation: the beginning of a long story?

Abstract

Secondary mitral regurgitation (SMR) is the consequence of the mal-coaptation of the mitral valve leaflets, due to substantial alteration (mostly dilatation and flattening) of the mitral annulus geometry and/or an imbalance between closing and tethering forces [1]. SMR is a frequent clinical issue. Reported in up to 30% of heart failure patients, SMR is an independent marker associated with the risk of death or rehospitalisation [2]. MR itself worsens the left ventricular (LV) function and dilatation, hence increasing the MR’s severity, setting up a vicious circle. Therefore, in addition to amelioration of symptoms, it seems attractive to hypothesise that treating the MR could improve patient’s prognosis. Treatment of SMR was mainly based on optimal medical therapy, including cardiac resynchronisation therapy when appropriate [3]. A surgical treatment has been evaluated mainly in ischaemic heart diseases. The results are limited because of 1an important morbidity and mortality in patients with high surgical risk [4]; 2a high recurrence of MR after conservative surgery [5]; 3limited benefits in terms of survival and functional results essentially in the most ‘severe’ patients (e.g. cases with poorer left ventricular function) [6]. Thus, surgical treatment of SMR (mitral valve replacement mostly) is essentially restricted to lowerrisk patients having greater MR degree, and mainly when concomitant revascularization is feasible [3]. In the last decade, the MitraClip therapy emerged as an attractive treatment of MR: in the EVEREST II randomised trial, this percutaneous edge-to-edge repair showed similar improvements in clinical outcomes, with significantly superior safety (rate of blood transfusion and duration of mechanical ventilation), compared to surgery in 279 patients with symptomatic moderate to severe primitive or secondary MR [7]. Since this publication, long term worldwide results reported the persistence of the result at 5 years [8], as well as the safety of this technique in the hands of trained teams, even in high risk populations [9,10]. Interestingly, in a recent meta-analysis of 3253 patients treated by MitraClip therapy for SMR, a clear functional benefit has been reported. In addition, behind a reduction of the grade of the MR, a reverse left ventricular (LV) remodelling, and a reduction of pulmonary pressure, at follow-up, has been demonstrated. However, the prognosis of those treated patients remained poor with an 18% mortality at 12 months [11]. Another meta-analysis of 6 retrospective studies with a propensity-matched analysis showed that patients treated by MitraClip for a SMR had a better prognosis in term of mortality and re-hospitalization (median follow-up of 400-day), compared to patients treated by optimal medical treatment alone [12]. Based on these premises, the results of the two large multicenter randomised trials below were more than expected. The COAPT trial showed for the 1st time, on 614 patients, a clear benefit of a MitraClip therapy in SMR, on the top of an optimal medical therapy (OMT): the primary endpoint (all hospitalisations for heart failure within 24 months), was significantly reduced in the MitraClip group (HR 0.53; 95 CI 0.40-0.70; p> .001), with an impressive number needed to treat (NNT) of 3.1. It also showed a significant reduction of the allcause mortality in the MitraClip group (HR 0.62; 95 CI 0.46-0.82; p< .001), with a NNT of 5.9, as well as an improvement in quality of life, NYHA functional class, and functional parameters [13]. On the other hand, the MITRA-FR trial failed to show any 12-months clinical benefit of an additional MitraClip therapy on the top of an OMT, in 304 patients with severe symptomatic SMR [14].