Percutaneous transcatheter valve replacement in individuals with mitral regurgitation unsuitable for surgery or transcatheter edge-to-edge repair: a prospective, multicountry, single-arm trial

Background Patients with severe mitral regurgitation are frequently not candidates for surgery or transcatheter edge-to-edge repair (TEER). We aimed to evaluate 1-year outcomes of a novel percutaneous transseptal transcatheter mitral valve replacement (TMVR) system in patients unsuitable for surgery or TEER. Methods In this prospective, multicentre, single-arm, pivotal trial, adult patients (aged ≥18 years) with symptomatic moderate-to-severe or severe mitral regurgitation who were not suitable for surgery or TEER were recruited at 56 centres in six countries (the USA, Canada, the UK, the Netherlands, Israel, and Australia). Eligible patients were treated with TMVR using the SAPIEN M3 system (Edwards Lifesciences, Irvine, CA, USA). The primary endpoint was a non-hierarchical composite of all-cause mortality and heart failure rehospitalisation at 1 year in the as-treated population, compared with a prespecified performance goal of 45%. This trial is registered with ClinicalTrials.gov , NCT04153292 , and is ongoing. Findings Between June 9, 2020, and Oct 10, 2023, 1171 patients were screened, of whom 299 were treated. Follow-up data were available for 283 (95%) patients at 30 days and 243 (81%) at 1 year (median follow-up 1·4 years [IQR 1·0–2·1]). The median age was 77·0 years (IQR 70·0–82·0), 152 (51%) participants self-reported as male and 147 (49%) as female, and the mean Society of Thoracic Surgeons predicted risk of 30-day mortality for mitral valve replacement was 6·6%. There were no intraprocedural deaths, no instances of left ventricular outflow tract obstruction causing haemodynamic compromise, and no conversions to surgery. The primary endpoint rate of 25·2% (95% CI 20·6–30·6) was significantly lower than the prespecified performance goal of 45% (p<0·0001). Interpretation Percutaneous transseptal TMVR with the SAPIEN M3 system effectively reduced mitral regurgitation with low rates of complications and mortality. These findings support percutaneous TMVR with the SAPIEN M3 system as a therapeutic option for patients who are unsuitable for surgery or TEER. Funding Edwards Lifesciences.