Percutaneous Transcatheter Mitral Valve Replacement for Symptomatic Mitral Regurgitation

Background Transcatheter mitral valve replacement (TMVR) is an approved treatment option for select high-risk patients with symptomatic mitral regurgitation (MR). The main cohort of the ENCIRCLE trial, evaluating fully percutaneous transseptal TMVR with the SAPIEN M3 system, demonstrated 13.9% mortality, significant MR reduction, and improved functional and health status outcomes at 1 year. Objectives We report 2-year outcomes from the main cohort of the ENCIRCLE trial. Methods Eligible symptomatic patients with ≥3+ MR who were not suitable for surgery or transcatheter edge-to-edge repair underwent TMVR with the SAPIEN M3 system. Independent study oversight included an echocardiographic core laboratory and a clinical events committee. Endpoints included the nonhierarchical composite rate of all-cause mortality or heart failure hospitalization (HFH) as well as clinical, echocardiographic, functional, and health status outcomes. Results A total of 299 patients were treated, with 2-year follow-up data available for 202 of 210 eligible patients (96.2%). Mean age was 75.5 ± 9.3 years, 50.8% were men, and the mean Society of Thoracic Surgeons Predicted Risk of Mortality score for mitral valve replacement was 6.6% ± 4.1%. At 2 years, MR reduction was sustained, with MR ≤1+ in 97.0% patients (*P* < 0.001). The 2-year composite rate of all-cause mortality or HFH was 35.6% (25.1% all-cause mortality, 23.0% HFH). In a 365-day landmark analysis, 1- to 2-year rates were 13.0% for all-cause mortality and 10.6% for first HFH. At 2 years, the rates of disabling stroke, clinically significant valve thrombosis, and hemolysis requiring intervention were 6.6%, 7.1%, and 7.6%, respectively. There were no instances of clinically significant left ventricular outflow obstruction. Improvements in functional and health status outcomes were sustained with 87.0% of patients in NYHA functional class I/II (*P* < 0.001) and a mean Kansas City Cardiomyopathy Questionnaire overall summary score increase of 17.2 points (*P* < 0.001). The 6-minute walk distance increased by +9.0 ± 97.3 m compared to baseline (*P* = 0.246). Conclusions The 2-year results of the ENCIRCLE trial demonstrated durable near MR elimination with sustained improvements in functional and health status outcomes in surviving patients. These findings support transseptal TMVR as a therapeutic option for carefully selected patients with symptomatic MR. (The ENCIRCLE Trial [ENCIRCLE]; [NCT04153292](https://clinicaltrials.gov/study/NCT04153292))