Large Trials Support Mitral Valve Repair in Heart Failure

LONDON — Opinions about the relative value of interventions to control mitral regurgitation secondary to heart failure might be altered by two large randomized trials. The RESHAPE-HF2 trial showed that mitral transcatheter edge-to-edge repair (M-TEER) has an advantage over guideline-recommended medical therapy alone, and the MATTERHORN trial showed M-TEER to be noninferior to surgery.

In the RESHAPE-HF2 trial, 505 patients with moderate to severe functional mitral regurgitation were randomized to the M-TEER group, in which patients received mitral valve repair with the MitraClip device (Abbott) plus guideline-recommended medical therapy, or to the control group, in which patients were treated with guideline-recommended medical therapy alone.

At 24 months, the primary endpoint of cardiovascular death or hospitalization for heart failure was 30% lower in the M-TEER group than in the control group (hazard ratio, 0.64; P = .002), reported Stefan D. Anker, MD, PhD, professor of tissue homeostasis in cardiology and metabolism at Charité – Universitätsmedizin, Berlin, Germany.

Both the RESHAPE-HF2 and MATTERHORN trials were presented at the European Society of Cardiology (ESC) Congress 2024, and both were simultaneously published in The New England Journal of Medicine.

Earlier trials helped set the stage for RESHAPE-HF2 and MATTERHORN and were an important part of the conversation at ESC.

The Trials Leading Up to RESHAPE-HF2 and MATTERHORN

Six years ago, the COAPT trial showed a similar benefit to the RESHAPE-HF2 trial in 614 patients, but all had severe disease.

COAPT was followed by the much smaller MITRA-FR trial, and the results were disappointing. M-TEER failed to show a benefit relative to guideline-recommended medical therapy alone in 304 patients with less severe mitral regurgitation than in those randomized in COAPT.

However, although RESHAPE-HF2 enrolled more patients with moderate severity mitral regurgitation, MITRA-FR has now become the outlier of these three trials, said Gregg W. Stone, MD, director of academic affairs at the Mount Sinai Heart Health System in New York City, who was the ESC invited discussant for the trial.

Stone, who was the principal investigator of COAPT, provided several potential explanations for why MITRA-FR failed to show benefit but said that RESHAPE-HF2 changes the landscape not only for patients with severe mitral regurgitation but also possibly for those with milder forms.

Convinced that RESHAPE-HF2 and COAPT together now make M-TEER a standard for patients with severe disease, Stone said he agrees with Anker that RESHAPE-HF2 “opens the door” for the treatment of moderate mitral regurgitation.

Stone called for a trial comprising exclusively patients with moderate mitral regurgitation to prove this hypothesis.

MATTERHORN Compares Surgery With M-TEER

In MATTERHORN, 210 patients with heart failure and mitral regurgitation who had persistent symptoms were randomized to M-TEER with the MitraClip device or to surgical valve replacement. The study was designed as a noninferiority comparison of the primary composite endpoint of death, hospitalization for heart failure, mitral valve reintervention, implantation of an assist device, and stroke.

After 1 year, there were fewer primary events in the M-TEER group than in the surgery group (16.7% vs 22.5%). This met the prespecified definition of noninferiority by a highly statistically significant margin (P < .0001), said Volker Rudolph, MD, PhD, an interventional cardiologist at the Heart and Diabetes Center in Bad Oeynhausen, Germany, who presented the data.

Data from the MATTERHORN study should be considered less compelling, according to Jo Chikwe, MD, who is chair of the Department of Cardiac Surgery at Cedars-Sinai Medical Center in Los Angeles, and the ESC invited discussant for the trial.

Chikwe outlined numerous problems with the design and conclusions of the trial.

Conclusions Questioned

First, she questioned the choice of a 17.5% noninferiority margin, which she considers too generous to prove noninferiority. In addition, she voiced concern about the relatively large 8% of patients lost to follow-up and the 3% of patients in the M-TEER group who required surgery during initial hospitalization. She said she considers these a source of bias that make the results difficult to interpret.

Perhaps most important, Chikwe said, is that a follow-up of 1 year is not enough to draw conclusions when comparing M-TEER with surgery, which is a potentially definitive repair. At 1 year, fewer patients in the M-TEER group than in the surgery group had mitral regurgitation of grade 2+ or lower (73% vs 98%).

She extrapolated COAPT data — using the progression of heart failure class from baseline to 1 year in the MATTERHORN trial — to predict a steep subsequent deterioration in both the treatment groups. By 3 years, she said, the majority of patients, regardless of treatment, would likely be in class III or higher heart failure or dead. By 4 years, she predicted the majority would be dead.

Outcomes in the surgery group of the MATTERHORN trial were worse than she would expect in a similar population treated at her own institution, so she concluded that, ultimately, the MATTERHORN data “are very far away from proving the noninferiority” of M-TEER over a follow-up period that is fair to long-term outcomes.