鶹ýӰ

Another Trial Sides With MitraClip for Functional Mitral Regurgitation

— RESHAPE-HF2 has provocative implications for a wider pool of TEER candidates

MedpageToday
ESC over a photo of ExCeL London conference and exhibition center.

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 .

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, 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 .

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 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.

  • author['full_name']

    Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine.

Disclosures

RESHAPE-HF2 was funded by Abbott Laboratories.

Anker disclosed grants and personal fees from Vifor and Abbott Vascular; personal fees for consultancies, trial committee work and/or lectures from Actimed, Astra Zeneca, Bayer, Bioventrix, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Cytokinetics, Edwards, Farraday Pharmaceuticals, GSK, HeartKinetics, Impulse Dynamics, Medtronic, Novartis, Novo Nordisk, Occlutech, Pfizer, Regeneron, Relaxera, Repairon, Scirent, Sensible Medical, Servier, Vectorious, and V-Wave; and being named co-inventor of two patent applications regarding MR-proANP.

Obadia reported serving on advisory boards or receiving grants from Abbott, Carmat, Edwards, Jenscare, Tricare; and consulting for Delacroix Chevalier and Landanger.

Stone has received speaker honoraria from Pulnovo, Medtronic, Amgen, Boehringer Ingelheim, Abiomed; has served as a consultant to CorFlow, Cardiomech, Robocath, Daiichi Sankyo, Ablative Solutions, Vectorious, Miracor, Apollo Therapeutics, Elucid Bio, Abbott, Cardiac Success, Occlutech, Millennia Biopharma, Remote Cardiac Enablement, Valfix, Zoll, HeartFlow, Shockwave, Impulse Dynamics, Adona Medical, Oxitope, HighLife, Elixir, Aria; and has equity/options from Cardiac Success, Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Valfix, Xenter. Dr. Stone's employer, Mount Sinai Hospital, receives research grants from Shockwave, Biosense-Webster, Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Vascular Dynamics, Pulnovo, V-wave and PCORI (via Weill Cornell Medical Center).

Bhavanadhar had no disclosures.

Primary Source

New England Journal of Medicine

Anker SD, et al "Transcatheter valve repair in heart failure with moderate to severe mitral regurgitation" N Engl J Med 2024; DOI: 10.1056/NEJMoa2314328.

Secondary Source

Journal of the American College of Cardiology

Anker MS, et al "Percutaneous transcatheter edge-to-edge repair for functional mitral regurgitation in heart failure: A meta-analysis of three randomized controlled trials" J Am Coll Cardiol 2024; DOI: 10.1016/j.jacc.2024.08.026.

Additional Source

Journal of the American College of Cardiology

Obadia J-F, et al "Plea for an in-depth analysis of the RESHAPE-HF2 results" J Am Coll Cardiol 2024; DOI: 10.1016/j.jacc.2024.08.030.

Additional Source

Journal of the American College of Cardiology

Source Reference: Stone GW and Bhavanadhar P "M-TEER for functional MR: Erasing all doubt" J Am Coll Cardiol 2024; DOI: 10.1016/j.jacc.2024.08.037.