In HF with secondary mitral regurgitation, percutaneous mitral valve repair did not improve 1-year clinical outcomes

Abstract

Question In symptomatic heart failure (HF) with severe, secondary mitral regurgitation (MR), what are the efficacy and safety of adding percutaneous mitral valve repair to medical therapy? Methods Design Randomized controlled trial (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation [MITRA-FR] trial). ClinicalTrials.gov NCT01920698. Allocation Concealed.* Blinding Blinded* (outcome adjudication committee). Follow-up period 12 months. Setting 37 centers in France. Patients 307 patients >18 years of age (mean age 70 y, 75% men, mean left ventricular ejection fraction [LVEF] 33%) who had echocardiography-confirmed severe secondary MR (regurgitant volume >30 mL/beat or effective regurgitant orifice area >20 mm2), LVEF 15% to 40%, and chronic HF symptoms (New York Heart Association functional class II to IV). Exclusion criteria included eligibility for mitral valve surgery. Intervention Percutaneous mitral valve repair, using the MitraClip device, plus guideline-based medical therapy (n =152), or guideline-based medical therapy alone (n =155). Outcomes Primary outcome was a composite of all-cause mortality or unplanned HF hospitalization. Other outcomes included components of the primary outcome, cardiovascular (CV) mortality, survival free of major adverse CV events (a composite of primary outcome events, stroke, or myocardial infarction), and periprocedural complications. 288 patients were needed to detect a 17% absolute reduction in the primary outcome from 50% in the medical therapy alone group (80% power, 2-sided =0.05), with 10% loss to follow-up. Patient follow-up 99% (intention-to-treat analysis). Main results The main results are in the Table. In the mitral valve repair group, implantation was attempted in 95% of patients, and 91% had 1 clip implanted. In patients with attempted implantation, periprocedural complications included bleeding (3.5%), atrial septum lesion or defect (2.8%), cardiogenic shock (2.8%), cardiac embolism (1.4%), and tamponade (1.4%). No patients had urgent conversion to heart surgery or {perioperative death}. Conclusion In heart failure with severe secondary mitral regurgitation, adding percutaneous mitral valve repair to medical therapy did not improve clinical outcomes at 1 year. Percutaneous mitral valve repair + medical therapy (MT) vs MT alone in HF with severe secondary mitral regurgitation Outcomes Event rates At 12 mo Percutaneous mitral valve repair + MT MT alone RRI (95% CI) Primary composite outcome 55% 51% 7.2% (15 to 29) All-cause mortality 24% 22% 9.5% (28 to 61) Unplanned HF hospitalization 49% 47% 8.9% (14 to 34) CV mortality 22% 20% 7.9% (31 to 64) Major adverse CV events 57% 51% 14% (8 to 36) CV = cardiovascular; HF = heart failure; other abbreviations defined in Glossary. RRI and CI calculated from MT-alone event rates and odds ratios or hazard ratios in article. All-cause mortality or unplanned HF hospitalization. All-cause mortality, stroke, myocardial infarction, or unplanned HF hospitalization. Commentary Functional or secondary MR occurs when coaptation of the leaflets is poor due to changes in the left ventricle. Potential causes include displacement of the papillary muscles, mitral annular dilation, and regional wall motion abnormalities that result in restriction of the mitral valve leaflets. Severe secondary MR occurs in about 25% of patients with HF and reduced ejection fraction (HFrEF) and is independently associated with a high mortality rate (40% to 50% at 3 years) (1). Whether fixing MR with a percutaneous transcatheter approach would affect symptoms, rehospitalization rates, or mortality was not previously known. 2 new trials now address this question and have different conclusions. Both trials enrolled patients who had symptomatic, moderate-to-severe or severe MR with reduced ejection fraction and were not considered surgical candidates. Mean ejection fraction, intensity of medical management, use of resynchronization therapy, and rates of coronary artery disease and atrial fibrillation at baseline were similar in both trials, as were the rates of death in control groups at 1 year (22% in MITRA-FR and 23% in COAPT). However, the mean effective regurgitant orifice (ERO) area at baseline was greater in COAPT than in MITRA-FR (mean 41 mm2 vs 31 mm2) (2). In addition, left ventricular end-diastolic volumes were smaller in COAPT than in MITRA-FR (101 mL/m2 vs 135 mL/m2) (2). This suggests that patients enrolled in COAPT had more severe MR but less compromised ventricles. In both trials, patient screening before randomization included core echocardiography laboratory assessment. COAPT included the likelihood of a successful procedure in the assessment. This contributed to a 58% exclusion rate in COAPT vs 32% in MITRA-FR. Both trials enrolled patients who remained symptomatic despite optimal guideline-directed medical therapy. In COAPT, the MitraClip group used more reninangiotensin system blockers than the control group at baseline (P =0.02), and the difference was consistent throughout the trial. Both trials used the same MitraClip device, which joins the anterior and posterior leaflet at the point of regurgitation, effectively creating a double orifice and reducing regurgitation. However, there were differences in technical success. In MITRA-FR, 9% of patients in the MitraClip group could not receive device implantation vs 5% in COAPT. Although COAPT followed patients for about twice as long (median 17 to 23 mo vs 1 y), differences in rehospitalization and all-cause mortality in COAPT were apparent early and persisted throughout the trial. In COAPT, we see the effect of MitraClip-mediated reduction in MR in carefully selected patients who were still symptomatic despite optimal use of devices and guideline-directed medical therapy. They also had worse MR (measured by severity in ERO) but ventricles that were less dilated (in other words, decompensation was probably less advanced) than patients in MITRA-FR. Given how much better patients in the COAPT trial fared with MitraClip vs optimal medical management and how few treatment options remain (left ventricular assist device or transplantation) for patients with HFrEF and severe MR, we now believe that patients similar to those in COAPT should be referred to a heart valve team (including HF specialists) for consideration of this procedure. Results of the RESHAPE-HF2 trial (ClinicalTrials.gov NCT02444338) and the 2-year results of MITRA-FR should be available soon, as well as results from trials of new transcatheter devices (Carillon, Cardioband, Mitralign) and other mitral valve prostheses. Trials of longer duration are also needed to test the durability of these devices. Meanwhile, European guidelines (3) give devices for secondary MR in HFrEF a IIb rating (level of evidence C) and US guidelines do not recommend them yet, although, given these results, this will probably change for a select group of MR patients.