Mechanical intervention of FMR: the game changers
Although long-term outcomes of surgical repair for primary MR have been excellent, treatment for FMR with valve repair or replacement has produced less favorable results. Both US and European guidelines currently recommend medical therapy as the initial strategy and mainstay of FMR management with CRT and revascularization as appropriate.7-9 In the 2017 American College of Cardiology/American Heart Association (ACC/AHA) valvular guidelines, the biggest change was a new recommendation that “it is reasonable to choose chordal-sparing MV replacement over downsized annuloplasty repair if an operation is considered for severely symptomatic patients (New York Heart Association (NYHA) class III-IV) with chronic severe ischemic MR (stage D) and persistent symptoms despite GDMT”.8This was based on remarkable findings of a cardiothoracic surgical trials network (CTSN) multicenter RCT showing that the recurrence rate of moderate-to-severe MR over 1 and 2 years was significantly higher in the restrictive annuloplasty repair group than in the replacement group, associated with a higher incidence of HF and rehospitalization.11,12 In addition, the recommendation for MV repair in patients with chronic, moderate ischemic MR undergoing coronary artery bypass grafting (CABG) changed from “may be considered” to “usefulness of MV repair is uncertain” (2b, Level B-R).8 This modification was largely based on another CTSN study demonstrating that the addition of restrictive MV annuloplasty to CABG did not add any survival benefit or reduce overall adverse events or readmissions.13,14 A superficial interpretation of these two CTSN trials favors replacement in patients with severe FMR. For moderate FMR, leaving it alone at the time of CABG seems to be reasonable.
The reality of the poor prognosis despite rigorous GDMT (and CRT when indicated) and the high proportion of advanced HF patients who are too risky or unsuitable for conventional surgery have stimulated rapid development of less-invasive transcatheter technologies. Currently, the most widely used TMVr device is the MitraClip (Abbott Vascular, Santa Clara, California). This transcatheter intervention produces an edge-to-edge leaflet coaptation and creates a double-orifice MV.44 The efficacy and safety of Mitraclip for moderate-to-severe FMR were evaluated in 2 large RCTs: MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) and COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy).15,16 Both trials randomized patients to MitraClip along with GDMT vs. GDMT alone. The MITRA-FR trial found no differences in a composite of death from any cause and readmissions for HF at 1 year, while the COAPT trial found a significant reduction in hospital readmissions for HF at 2 years and overall mortality. On the basis of the results of the COAPT trial, the FDA approved the MitraClip for the treatment of FMR in patients with HF who remain symptomatic despite GDMT.9 Consequently, new changes have been made in the most recently published “2020 Focused update of the 2017 ACC expert consensus decision pathway on the management of mitral regurgitation”,9 which supported the consideration of TMVr in the management of FMR.
However, the strikingly opposed findings across the 2 MitraClip RCTs, which used precisely the same device to reduce MR, have generated intense debate because these results cannot be simply explained by differences in trial design, length of follow-up, or statistical power.37 Intriguingly, an examination of the baseline characteristics of the patients participating in the 2 trials indicated that the studies included 2 distinctly different populations of patients with FMR.45,46 Patients enrolled in the COAPT trial had more severe FMR (EROA 41mm2 vs. 31mm2; RVol 60ml vs. 45ml) and less dilated ventricles (LVEDV index 101ml/m2 vs. 135ml/m2) than those in the MITRA-FR trial. According to the concepts of proportionate and disproportionate MR, it is evident that the patients in the MITRA-FR trial represent a population in which the MR is proportional to the ventricular dilatation and is a consequence, not a cause, of the ventricular disease. Therefore, these patients would generally respond favorably with an improved prognosis when treated with GDMT aiming at reducing the ventricular volume. In contrast, the patients in the COAPT trial had disproportionate degrees of FMR, with higher RVol for smaller ventricles, in which proper functioning of the MV apparatus is disproportionately undermined, leading to severe MR that cannot be explained by the degree of LV enlargement. These patients would be ideal candidates for mechanical interventions aimed at correcting the MR.37-39
Hence, the outcomes of recent surgical and transcatheter RCTs emphasized the importance of patient selection and, taken together, have delineated the beneficial role of MV intervention in FMR patients who have disproportionate regurgitation despite GDMT (or CRT when indicated). Concurrently, the effectiveness of MV intervention in patients with proportionate or non-severe MR is yet to be proven.47