ENCIRCLE: SAPIEN M3 System Transcatheter Mitral Valve Replacement Via Transseptal Access, two-year outcomes

doi:10.1016/j.jacc.2026.10.047

ENCIRCLE

Patient / Population Intervention / Exposure Comparison Outcome

In patients with symptomatic mitral regurgitation unsuitable for surgery or edge-to-edge repair, transseptal mitral valve replacement with the SAPIEN M3 system sustained reduction of mitral regurgitation to mild or less in 97.0% at 2 years, with a 35.6% rate of death or heart failure hospitalisation.

N

299patients

Design

Prospective, multicentre, single-arm study (Edwards; 54 sites in North America, Europe, Israel and Australia) of transseptal TMVR with the SAPIEN M3 system in patients unsuitable for surgery or TEER; failed-TEER and mitral annular calcification registries alongside

Endpoint

Death and heart failure rehospitalisation (primary at 1 year). TCT presents two-year outcomes

ResultThe 2-year composite rate of all-cause mortality or heart failure hospitalisation was 35.6% (25.1% all-cause mortality, 23.0% heart failure hospitalisation). In a 365-day landmark analysis, 1- to 2-year rates were 13.0% for all-cause mortality and 10.6% for first heart failure hospitalisation. MR ≤1+ in 97.0% of patients at 2 years (P < 0.001). Disabling stroke 6.6%, clinically significant valve thrombosis 7.1% and haemolysis requiring intervention 7.6%. No clinically significant left ventricular outflow obstruction. 87.0% of patients were in NYHA class I/II (P < 0.001) and the KCCQ overall summary score rose by a mean 17.2 points (P < 0.001). 6-minute walk distance changed by +9.0 ± 97.3 m (P = 0.246). Follow-up was available for 202 of 210 eligible patients (96.2%).

Webb J, Guerrero ME, et al. J Am Coll Cardiol. 2026; published online 3 November. 10.1016/j.jacc.2026.10.047

Discussion & critique

In patients unsuitable for surgery or edge-to-edge repair, near-elimination of mitral regurgitation and gains in symptoms and health status persisted to 2 years. Without a comparator, the 35.6% rate of death or heart failure hospitalisation, with deaths continuing between years 1 and 2, cannot be attributed to or against the device. The functional and quality-of-life gains are measured in survivors, and 6-minute walk distance did not improve significantly. Disabling stroke, valve thrombosis and haemolysis requiring intervention each affected about 7% of patients, and the abstract gives no data on durability beyond 2 years.