Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve - RESTOR-MV

Description:

Current treatment options for patients with left ventricular (LV) systolic dysfunction and functional mitral regurgitation (FMR) include medical therapy or surgery. Surgery can be coronary artery bypass grafting (CABG) (to revascularize viable myocardium and thus improve LV mechanics) and/or mitral valve (MV) repair/replacement. However, outcomes in this group of patients are still poor. The current trial sought to study the safety and efficacy of a novel LV reshaping device, Coapsys (Myocor, Inc., Maple Grove, MN) to treat FMR.

Hypothesis:

Surgery with the Coapsys device would be noninferior to CABG ± MV repair in patients with FMR undergoing cardiac surgery.

Study Design

  • Blinded
  • Randomized
  • Parallel
  • Stratified

Patient Populations:

  • ≥2+ MR
  • Need for concomitant CABG
  • LVEF ≥25%

    Number of screened applicants: 235
    Number of enrollees: 165
    Duration of follow-up: 28.3 months
    Mean patient age: 65.3 years
    Percentage female: 23%
    Ejection fraction: 37%
    NYHA class: II (41.2%), III (49%)

Exclusions:

  • Structural abnormality of the MV
  • Asymptomatic moderate MR
  • Transmural MI within 30 days
  • NYHA functional class IV

Primary Endpoints:

  • All-cause mortality
  • Primary adverse events (all-cause mortality, stroke, reoperation for bleeding, valvular dysfunction, life-threatening arrhythmias, or mechanical device failure)
  • Degree of MR

Secondary Endpoints:

  • NYHA functional class

Drug/Procedures Used:

Patients were allocated by the surgeon to either CABG + MV repair or CABG alone. In the CABG + MV repair stratum, subjects were randomized 1:1 to undergo CABG with mitral ring annuloplasty (control) or undergo CABG + Coapsys (treatment). In the CABG alone stratum, subjects were randomized 1:1 to CABG alone (control) or CABG + Coapsys (treatment).

The Coapsys consists of a single anterior pad and a dual-headed posterior pad (both extracardiac) connected by a flexible transventricular subvalvular chord. This thus reshapes the ventricle, compressing the mitral annulus and subvalvular apparatus to decrease FMR. The device is sized intraoperatively by shortening the chordal length of the device, thus drawing the pads together. Implantation is performed without cardiotomy or cardiopulmonary bypass.

Principal Findings:

A total of 165 patients were randomized, with 149 in the CABG + MV repair stratum (75 CABG + MV repair, 74 CABG + Coapsys) and 16 in the CABG alone stratum (8 CABG, 8 CABG + Coapsys). Mean LV ejection fraction (EF) was about 37% in both strata, with the majority of patients having New York Heart Association (NYHA) class II/III symptoms. The mean MR grade was 2.5 in the CABG + MV repair stratum, and 2.0 in the CABG alone stratum. About 50% had diabetes, 26% had renal insufficiency, 65% had a history of chronic heart failure, 59% had history of myocardial infarction (MI), and about 17% had undergone prior percutaneous coronary intervention; only two patients had undergone prior CABG. Cardiopulmonary bypass was necessary in all patients in the CABG + MV repair arm, but in only 31% of the CABG + Coapsys arm, and none in the CABG stratum.

Although initially designed to enroll at least 250 patients, the trial was terminated early in October 2008 as the sponsor failed to secure further funding for the study, at which point 165 patients had been randomized. An intention-to-treat analysis of all patients showed a survival advantage for the Coapsys treatment with a 2-year survival rate of 87% compared with 77% for the control patients (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.20-0.87, stratified log-rank test p = 0.038). Similar results were noted in the per-protocol analysis. Complication-free survival from any primary adverse event (all-cause mortality, stroke, reoperation for bleeding, valvular dysfunction, life-threatening arrhythmias, or mechanical device failure) was higher in the Coapsys arm (76% vs. 63%, HR 0.46, 95% CI 0.26-0.83, p = 0.022). Paradoxically, FMR at the end of 2 years was significantly lower in the control arm, as compared with the Coapsys arm (mean grade 0.35 vs. 1.24), with a greater reduction from baseline to 1 year in the control arm, as compared with Coapsys (p < 0.0001). In both the Coapsys and control arms, a significant reduction in LV end-diastolic dimension was noted, although this was higher in the Coapsys arm.

Interpretation:

The results of the RESTOR-MV trial indicate that although MR reduction is greater with CABG + MV repair, as compared with the Coapsys device, the latter is associated with overall improvements in LV dimensions, and clinically, with a higher survival and freedom from adverse events at 2 years. The Coapsys device is designed to have a positive reshaping effect on the left ventricle and the mitral annulus, and can be done off-pump, and is thus different from other available methods/devices.

The recent STICH trial noted no improvement in outcomes with LV volume reduction strategies using surgical reconstruction. Further data and experience with the Coapsys device are necessary. More recently, the EVEREST II trial noted promising results in patients with severe MR with the percutaneous MitraClip, as compared with MV surgery. Further data comparing these various new technologies are also necessary.

One limitation of this trial is that they did not include patients with severe LV dysfunction (EF <25%), who are more likely to have severe FMR due to LV dilation. Thus, this limits the generalizability of this trial.

References:

Grossi EA, Patel N, Woo J, et al., on behalf of the RESTOR-MV Study Group. Outcomes of the RESTOR-MV (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) trial. J Am Coll Cardiol 2010;56:1984-1993.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Structural Heart Disease, Mitral Regurgitation

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Mitral Valve Insufficiency, Heart Valve Prosthesis Implantation, Percutaneous Coronary Intervention, Equipment Failure, Renal Insufficiency, Reoperation, Survival Rate, Heart Failure, Cardiopulmonary Bypass, Confidence Intervals, Cardiac Surgical Procedures, Coronary Artery Bypass, Diabetes Mellitus


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