RESHAPE-HF2 Shows Clear Benefit of MitraClip for Functional Mitral Regurgitation

The RESHAPE-HF2 trial, presented at ESC 2024, offers further insights into the transcatheter management of patients with heart failure with reduced ejection fraction (HFrEF) and moderate-to-severe functional mitral regurgitation (FMR). The trial demonstrated that transcatheter mitral valve edge-to-edge repair (M-TEER) with the MitraClip device, in combination with guideline-recommended medical therapy, significantly reduced heart failure hospitalizations and improved health status compared to medical therapy alone. The results further support M-TEER for select patients with HFrEF and FMR

Functional mitral regurgitation is a frequent complication in heart failure, and prior randomized trials have shown conflicting results regarding the benefit of M-TEER. The MITRA-FR trial (2018) showed no significant reduction in mortality or heart failure hospitalization with M-TEER compared to medical therapy, while the COAPT trial (2018) demonstrated substantial benefits, including reductions in both hospitalizations and all-cause mortality. The discordant findings have been attributed to differences in patient selection, baseline medical therapy, and severity of FMR. Guidelines currently recommend M-TEER in select patients with symptomatic heart failure and moderate-severe secondary MR who remain symptomatic despite optimal medical therapy, particularly those at high surgical risk.

RESHAPE-HF2 was a multicenter, randomized trial that enrolled 505 patients across 30 sites in 9 countries. Participants had symptomatic heart failure, grade 3+ or 4+ functional MR, and a left ventricular ejection fraction between 20% and 50%, despite being on guideline-directed medical therapy. Patients were randomized in a 1:1 ratio to M-TEER plus medical therapy (device group) or medical therapy alone (control group). The trial’s three primary endpoints were the rate of first or recurrent hospitalization for heart failure or cardiovascular death at 24 months, first or recurrent heart failure hospitalization at 24 months, and change in health status at 12 months as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ-OS).

The mean age of participants was 70 years, with 20% of patients being women. Ischemic cardiomyopathy was present in 65% of the patients. The median left ventricular ejection fraction (LVEF) was 31%, indicating moderate to severe systolic dysfunction, and the median regurgitant volume was 36 mL. A large proportion of patients (66%) had been hospitalized for heart failure within the previous year, and nearly half of the participants had atrial fibrillation.

The results were significant. At 24 months, the composite endpoint of heart failure hospitalization or cardiovascular death occurred at a rate of 37.0 events per 100 patient-years in the TMVr group, compared to 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% CI, 0.48 to 0.85; p=0.002). The rate of first or recurrent heart failure hospitalizations was also lower in the TMVr group (26.9 vs. 46.6 events per 100 patient-years; rate ratio, 0.59; 95% CI, 0.42 to 0.82; p=0.002). Furthermore, patients in the device group experienced a significantly greater improvement in health status, with an average KCCQ-OS score increase of 21.6 points compared to 8.0 points in the control group (mean difference, 10.9 points; p<0.001). Safety outcomes were favorable, with device-related adverse events occurring in only 1.6% of patients.

Unlike the MITRA-FR trial, which failed to show a benefit, RESHAPE-HF2 confirms a clear reduction in heart failure hospitalizations and improvement in patient-reported outcomes. Unlike COAPT, RESHAPE-HF2 did not demonstrate a mortality benefit, perhaps related to less severe heart failure or FMR at baseline. Still, the reductions in hospitalizations and symptom burden are clinically meaningful, particularly for patients with high morbidity from recurrent hospitalizations. Patients with heart failure hospitalization in the prior year derived more significant benefits. Interestingly, the mean effective regurgitant orifice area (EROA) for RESHAPE-HF2 (0.25 cm²) was lower than in MITRA-FR (0.31 cm²) or COAPT (0.40 cm²), indicating benefit with lower degrees of FMR.

In clinical practice, the RESHAPE-HF2 results provide strong support for M-TEER as a therapeutic option for patients with heart failure and significant functional MR who are not candidates for surgery. The trial adds to the growing evidence suggesting that appropriately selected patients with functional MR may benefit substantially from M-TEER. Guideline-directed medical therapy in collaboration with heart failure specialists and treatment decisions guided by expert heart teams remain vital to realizing the fullest benefit from M-TEER.

 Reference:

Anker SD, Friede T, von Bardeleben RS, et al. Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation. N Engl J Med. 2024; DOI:10.1056/NEJMoa2314328.