Results from a pivotal clinical trial to evaluate the safety and efficacy of a fully percutaneous transseptal mitral valve replacement (TMVR) procedure—Sapien M3 (Edwards Lifesciences)—in patients with symptomatic, moderate-to-severe mitral regurgitation (MR) who are not candidates for conventional surgery or transcatheter edge-to-edge repair (TEER) procedures, demonstrated effective MR reduction with low rates of complications and mortality.
One-year data from the ENCIRCLE trial, presented by David Daniels (Sutter Health, San Francisco, USA) during a late-breaking trials session at the 2025 Transcatheter Cardiovascular Therapeutics (TCT) conference (25–28 October, San Francisco, USA), simultaneously published in The Lancet, demonstrated low rates of death and heart failure hospitalisation for patients treated with the device.
Sapien M3 is delivered transfemorally in a procedure that involves two steps, delivering the dock and then the valve to completely replace the mitral valve. The dock wraps around the native mitral leaflets which pulls them and the chordae inward toward the centre of the dock, bringing the papillary muscles closer together. The dock creates a stable and consistent landing zone for placing the Sapien M3 valve.
Trialists screened a total of 1,171 patients were at 56 sites in the USA, Canada, Europe, Israel and Australia. Thirty-five percent of those screened were excluded based on anatomic eligibility criteria. Ultimately, a total of 299 patients with mitral regurgitation (MR) ≥3+, New York Heart Association (NYHA) class ≥II, unsuitable for surgery or commercially available transcatheter treatment options due to clinical, anatomic, or technical considerations, were treated. Of these, 287 patients had a valve implanted. Follow up was completed at 30 days, six months and one year.
The primary endpoint was the composite of all-cause mortality and rehospitalisation for heart failure at one year compared to a pre-specified performance goal of 45%. After one year, the composite event rate was 25.2%. All-cause death and heart failure hospitalization rates were 13.9% and 16.7%, respectively.
Pre-specified secondary endpoints included improvement in MR grade, NYHA class, Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS), and Left Ventricular End Diastolic Volume index (LVEDVi) at one year.
The study found that all patients had improvement in MR grade with more than 95% of patients having ≤1+ total MR at 30 days and one year. NYHA improvement was observed in 73.4% of patients at one year, and ~88% of patients were considered as having NYHA class I or II at one year.
The improvement in KCCQ-OS was 18.4±1.68 with ~43% of patients having ≥20-point score improvement at one year. Rates of stroke, clinically significant leaflet thrombosis, and hemolysis were 9.3%, 6.7%, and 7.1%, respectively at one year.
“Percutaneous transseptal TMVR had a low mortality rate while providing a significant reduction in mitral regurgitation severity and providing meaningful and durable improvements in functional status and quality of life,” said Daniels. “These findings will help guide clinical practice by providing an alternative treatment option for patients who are not suitable for conventional surgery or TEER procedures.”
The study was funded by Edwards Lifesciences.
