Randomized Investigation of the MitraClip Device in Heart Failure: Second Trial in Patients With Clinically Significant Functional Mitral Regurgitation - RESHAPE-HF2

Aug 31, 2024
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Abbott Laboratories
Date Presented:
08/31/2024
Date Published:
08/31/2024
Original Posted Date:
08/31/2024
References

Contribution To Literature:

The RESHAPE-HF2 trial showed that M-TEER using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality at 2 years in symptomatic HF patients with grade 3-4+ MR.

Description:

The goal of the trial was to assess the safety and efficacy of mitral transcatheter edge-to-edge repair (M-TEER) using MitraClip among symptomatic heart failure (HF) patients with secondary mitral regurgitation (MR).

Study Design

Patients with HF and grade 3-4+ MR who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT) were randomized to M-TEER with MitraClip + GDMT (n = 250) versus GDMT alone (n = 255). This trial had an open-label design.

  • Total screened: 621
  • Total number of enrollees: 505
  • Duration of follow-up: 24 months (median 18.8 months)
  • Mean patient age: 70 years
  • Percentage female: 20%

Inclusion criteria:

  • Signs and symptoms of HF despite GDMT
  • Left ventricular ejection fraction (LVEF) of 20-50%
  • Moderate-to-severe (3+) or severe (4+) secondary MR 
  • Within 90 days before enrollment, either a hospitalization for HF or an elevated plasma natriuretic peptide concentration (a B-type natriuretic peptide [BNP] level of ≥300 pg/mL or an N-terminal pro–BNP [NT-proBNP] level of ≥1000 pg/mL)

Exclusion criteria:

  • Mitral surgery indicated
  • Degenerative mitral valve disease and any of the following procedures performed within 90 days before enrollment: percutaneous coronary intervention (PCI), cardiovascular (CV) surgery, or atrial fibrillation ablation

Other salient features/characteristics:

  • Prior myocardial infarction: 55%, prior PCI: 48%, prior coronary artery bypass grafting (CABG): 26%
  • Ischemic HF: 65%
  • HF hospitalization within 1 year: 66%
  • Median EF: 32%
  • Echo: effective regurgitant orifice area (EROA): 0.23 cm2, median regurgitation volume: 36 mL
  • Final MR >2+ in MitraClip arm: 7.9%

Principal Findings:

The primary endpoint, rate of first or recurrent HF hospitalization or CV death at 24 months, for MitraClip + GDMT vs. GDMT, was 37.0 vs. 58.9 events per 100 patient-years (rate ratio [RR] 0.64, 95% confidence interval [CI] 0.48-0.85, p = 0.002; number needed to treat = 5.1).

  • First or recurrent HF hospitalization: 26.9 vs. 46.6 events per 100 patient-years (p = 0.002)
  • Mean change from baseline in Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ­-OS): 21.6 vs. 8 (p < 0.001)

Secondary outcomes for MitraClip + GDMT vs. GDMT:

  • MR ≤2+ at 12 months: 90.4% vs. 36.1% (p < 0.001)
  • Mean change in 6-minute walk distance from baseline to 12 months: 34.0 vs. 5.1 (p = 0.05)
  • All-cause mortality: 22.3% vs. 29.6% (p = 0.09)
  • CV mortality: 17.8% vs. 20.4% (p = 0.43)

Hospitalization data: Time to first event of CV death or HF hospitalization (hazard ratio [HR] 0.65, 95% CI 0.49-0.85, p = 0.002), the rate of recurrent CV hospitalizations (RR 0.75, 95% CI 0.57-0.99, p = 0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR 0.74, 95% CI 0.57-0.95, p = 0.017), and of recurrent CV death and CV hospitalizations (RR 0.76, 95% CI 0.58-0.99, p = 0.040), were all lower in the M-TEER group. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% vs. 17.4% of follow-up time, p < 0.0001; 1,067 vs. 1,776 total days lost, p < 0.0001). History of ≥1 HF hospitalization before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (p for interaction = 0.03) and of recurrent HF hospitalizations within 24 months (p for interaction = 0.06).

Interpretation:

The results of this trial indicate that M-TEER using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality at 2 years in symptomatic HF patients with grade 3-4+ MR. The majority of benefit was related to a reduction in HF hospitalization. Significant improvements were noted in quality-of-life measurements and other patient-centered outcomes. Benefit was greater among those with a history of HF hospitalization within the past year.

These findings confirm the results of the COAPT trial, which also noted a benefit with M-TEER over GDMT alone. In contrast, the MITRA-FR trial did not show a benefit in this patient population. Interestingly, the EROA in the RESHAPE-HF 2 trial was closer to MITRA-FR (~0.25 cm2) than COAPT (0.4 cm2) suggesting less severe MR at baseline, but a benefit was nonetheless noted.

References:

Anker SD, Friede T, von Bardeleben RS, et al., for the RESHAPE-HF2 Investigators. Transcatheter Valve Repair in Heart Failure With Moderate to Severe Mitral Regurgitation. N Engl J Med 2024;Aug 31:[Epub ahead of print].

Ponikowski P, Friede T, von Bardeleben RS, et al. Hospitalization of Symptomatic Patients With Heart Failure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2. J Am Coll Cardiol 2024; Aug 31:[Epub ahead of print].

Presented by Dr. Stefan Anker at the European Society of Cardiology Congress, London, UK, August 31, 2024.

Clinical Topics: Heart Failure and Cardiomyopathies, Valvular Heart Disease, Acute Heart Failure, Mitral Regurgitation

Keywords: Heart Failure, Mitral Valve Insufficiency, ESC24, ESC Congress


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