ENCIRCLE Evaluates Edwards Sapien M3 TMVR System for MR Reduction

October 27, 2025—Results from the ENCIRCLE pivotal clinical trial demonstrated effective reduction of mitral regurgitation (MR) with low rates of complications and mortality using a fully percutaneous transseptal mitral valve replacement (TMVR) procedure in patients with symptomatic, moderate-to-severe MR who are not candidates for conventional surgery or transcatheter edge-to-edge repair procedures.

The ENCIRCLE trial is evaluating the safety and efficacy of fully percutaneous TMVR using the balloon-expandable, dedicated Sapien M3 mitral transcatheter heart valve (Edwards Lifesciences). The device is composed of and the Sapien M3 dock, which is designed as a landing zone to anchor the valve and valve system.

The findings were reported by David Daniels, MD, et al at the TCT 2025 scientific symposium and published simultaneously by Professor Mayra E. Guerrero, MD, et al in The Lancet.

As summarized in the TCT press release, the ENCIRCLE trial investigators treated 299 patients who had MR ≥ 3+, New York Heart Association (NYHA) class ≥ II, and were unsuitable for surgery or commercially available transcatheter treatment options because of clinical, anatomic, or technical considerations. Of these 299 patients, 287 underwent valve implantation. Follow-up was completed at 30 days, 6 months, and 1 year. The primary endpoint was a composite of all-cause mortality and rehospitalization for heart failure at 1 year compared to a prespecified performance goal of 45%.

The 1-year primary endpoint findings included the following:

• Composite event rate, 25.2% (95% CI, 20.6-30.6; P < .0001)
• All-cause death rate, 13.9%
• Heart failure hospitalization rate, 16.7%

For the prespecified secondary endpoints of improvement in MR grade, NYHA class, Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS), and left ventricular end-diastolic volume index at 1 year, the investigators reported the following:

• All patients had improvement in MR grade with more than 95% of patients having ≤1+ total MR.
• NYHA improvement observed in 73.4% of patients (P < .001), with approximately 88% of patient considered as having NYHA class I or II.
• The improvement in KCCQ-OS was 18.4 ± 1.68 (P < .001) with approximately 43% of patients having ≥ 20-point score improvement.
• Rates of stroke, clinically significant leaflet thrombosis, and hemolysis were 9.3%, 6.7%, and 7.1%, respectively.