Another Trial Sides With MitraClip for Functional Mitral Regurgitation

LONDON — Despite another positive trial, controversy rages on over transcatheter edge-to-edge repair (TEER or M-TEER) in people with symptomatic heart failure (HF) and functional mitral regurgitation (MR).

All three primary endpoints of RESHAPE-HF2 supported significant clinical benefit to the MitraClip procedure in a population with various stages of MR, predominantly severe, reported Stefan Anker, MD, PhD, of Charité Universitätsmedizin Berlin, in a presentation at the European Society of Cardiology (ESC) meeting:

• Composite of first or recurrent hospitalization for HF or cardiovascular death during 24 months: 37.0 vs 58.9 events per 100 person-years (RR 0.64, 95% CI 0.48-0.85)
• Rate of first or recurrent hospitalization for HF during 24 months: 26.9 vs 46.6 events per 100 person-years (RR 0.59, 95% CI 0.42-0.82)
• Change from baseline to 12 months on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) scale: increase of 21.6 vs 8.0 points on average (P<0.001)

During a press conference, Anker called these “clinically meaningful and important differences” favoring TEER over medical therapy alone. Results were simultaneously published in the New England Journal of Medicine.

As such, RESHAPE-HF2 “may have removed all doubt about the benefits of M-TEER in selected symptomatic HF patients with moderate-to-severe (3+) or severe (4+) MR,” Gregg Stone, MD, and Bhavanadhar Penta, MBBS, both of Icahn School of Medicine at Mount Sinai in New York City, commented in the Journal of the American College of Cardiology (JACC).

More provocative, however, was Anker and colleagues’ suggestion of a more liberal use of this technology, given the benefits seen with RESHAPE-HF2’s population of relatively less sick people compared with the foundational TEER studies (despite the trialists’ initial intentions, most participants had MR grade 1+ or lower in severity, or an effective regurgitant orifice area <0.30 cm²).

“A broader application of M-TEER for heart failure with functional MR of less than severe disease grade may be appropriate and deserves further study,” Anker said, although he declined to elaborate on how big the candidate pool could ultimately get.

Importantly, however, RESHAPE-HF2 had been stopped early because of difficult enrollment. It was also undermined by the multiplicity of endpoints and various protocol modifications made during study conduct, cautioned Jean-François Obadia, MD, PhD, of Louis Pradel Hospital in Lyon, France, and colleagues in a separate JACC editorial.

Some had hoped that this trial would be a tie-breaker between two conflicting studies in functional MR, both dating back to 2018. COAPT showed that MitraClip TEER reduced HF hospitalizations within 24 months over medical therapy alone, whereas the MITRA-FR trial found that the MitraClip was of no additional help for cutting 12-month all-cause mortality and unplanned HF hospitalization.

“Several hypotheses have been proposed to explain these discordant results, including differences in the severity of heart failure, medical treatment, and the mechanisms underlying functional mitral regurgitation,” Anker and colleagues recalled.

Despite the lingering controversy over the clinical benefits of TEER for functional MR, U.S. and European guidelines already give mitral TEER a class IIa recommendation for COAPT-like patients.

“[E]xpansion of this indication to a cohort with moderate (2+) MR must await the results from an appropriately powered dedicated randomized trial in this lower-risk but more prevalent patient population,” according to Stone and Penta.

Similarly, the suggestion to widen the pool of TEER candidates was shot down by Obadia and colleagues in their editorial. “Based on the results of RESHAPE-HF2, we cannot condone more liberal use of TEER as treatment of secondary MR, which contradicts the current guidelines. It is crucial to emphasize that the role of the Heart Team remains critical, and a tailored approach for each patient remains necessary,” they wrote.

RESHAPE-HF2 investigators had sought to enroll people with grade 3+ or 4+ functional MR from nine countries. They ended up with 505 individuals randomized (mean age 70, approximately 80% men). Echocardiography showed that 74.5% actually had grade 1+ or lower MR (mild), 17.7% grade 2+ MR (moderate), 4.1% grade 3+ MR (moderate-to-severe), and 3.7% grade 4+ MR (severe).

Even so, this cohort went on to be assigned guideline-recommended medical therapy with or without an additional MitraClip procedure. Follow-up lasted 18.8 months on average.

Anker’s group reported that the incidence of MitraClip-related safety events reached 1.6% of patients. These included two cases of hematoma, one pericardial effusion, and one right atrial perforation resulting in thoracotomy after MitraClip placement.

Separately, a study-level meta-analysis in JACC of MITRA-FR, COAPT, and RESHAPE-HF2 was attempted in an accompanying report. In this analysis, also published by JACC, investigators found that TEER was associated with a borderline reduction of HF hospitalizations through 24 months (HR 0.69, 95% CI 0.49-0.97) but no significant effect on all-cause mortality (HR 0.76, 95% CI 0.57-1.01) or cardiovascular mortality (HR 0.77, 95% CI 0.56-1.06).

Anker stressed the importance of a patient-level meta-analysis to draw more definitive conclusions. He said his group already has an agreement to share data with the MITRA-FR group, but the COAPT side has not committed.

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