Results from ENCIRCLE Announced at TCT 2025 Published Simultaneously in The Lancet
SAN FRANCISCO – OCTOBER 27, 2025 – Results from a pivotal clinical trial to evaluate the safety and efficacy of a fully percutaneous transseptal mitral valve replacement (TMVR) procedure 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.
Findings were reported today at TCT® 2025, the annual scientific symposium of the Cardiovascular Research Foundation® (CRF®) and published simultaneously in The Lancet. TCT is the world’s premier educational meeting specializing in interventional cardiovascular medicine.
TMVR is an emerging treatment option for patients with symptomatic mitral valve disease who are not candidates for surgery or commercially available transcatheter treatment options. Early generations of dedicated TMVR systems relied primarily on surgical transapical delivery of transcatheter heart valves (THV) which were associated with considerable risk including 30-day mortality up to 14%. The ENCIRCLE trial utilized the balloon-expandable, dedicated SAPIEN M3 mitral THV. The device is comprised of both the SAPIEN M3 dock, designed as a landing zone to anchor the valve, and valve system.
A total of 1,171 patients were screened at 56 sites in the United States, 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 MR ≥ 3+, 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 rehospitalization 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% (95% CI: 20.6-30.6; p <0.0001). All-cause death and heart failure hospitalization rates were 13.9% and 16.7%, respectively.
Pre-specified secondary endpoints included improvement in mitral regurgitation grade, New York Heart Association (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 (p<0.001), 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 (p<0.001) 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 David Daniels, MD, Chief of Structural Heart, Sutter Health. “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.
Dr. Daniels reported research/grant support from Edwards Lifesciences, royalties/patent beneficiary and executive role/ownership interest with Solo Pace Inc.
