Symptomatic mitral regurgitation (MR) in patients who are not candidates for surgery or transcatheter edge-to-edge repair (TEER) remains a highly complex clinical scenario associated with poor prognosis. Although TEER has demonstrated benefit in selected populations, a significant proportion of patients present with unfavorable anatomy or comorbidities that limit its indication.
The development of transcatheter mitral valve replacement (TMVR) via a fully percutaneous transseptal approach represents a potentially superior strategy, allowing for more effective elimination of regurgitation. However, to date, available evidence has mainly derived from feasibility studies or devices requiring transapical access, an approach associated with higher morbidity and mortality.
The ENCIRCLE study is the first trial to evaluate a fully percutaneous transseptal system in a native, non-calcified mitral valve. Its objective was to assess the safety and efficacy at one year of the SAPIEN M3 system for TMVR.
This was a prospective, multicenter, single-arm study conducted at 56 centers across six countries. Patients ≥18 years old, with NYHA functional class ≥II, moderate-severe or severe MR, and deemed unsuitable for surgical replacement or TEER by the Heart Team were included.
The primary endpoint was a non-hierarchical composite of all-cause death or heart failure (HF) rehospitalization at one year, compared against a prespecified performance goal of 45%.
Among 1,171 patients screened, 299 were treated, achieving a 96% successful device implantation rate. The mean age was 77 years; 71% had a high symptomatic burden (NYHA III–IV), and the mean STS score was 6.6%.
There were no intraprocedural deaths, no significant left ventricular outflow tract obstruction, and no conversions to surgery. Thirty-day mortality was 0.7%. At one year, the incidence of the primary endpoint was 25.2% (95% CI 20.6–30.6), significantly lower than the prespecified performance goal of 45% (p<0.0001). All-cause mortality was 13.9% (95% CI 10.4–18.5), and HF rehospitalization occurred in 16.7% (95% CI 12.8–21.6).
From a hemodynamic standpoint, 96% of patients had MR ≤1+ at one year (79% with no or trivial MR and 16% with mild MR). In addition, a reduction in left ventricular end-diastolic volume and an improvement in stroke volume were observed. Clinically, 73% improved by at least one NYHA functional class (p<0.0001), with a significant increase in quality of life as measured by the KCCQ-OS (mean increase of 18.4 points; p<0.0001).
Regarding adverse events, the rate of disabling stroke at one year was 3.9%, clinically significant valve thrombosis occurred in 6.7%, and mitral reintervention was required in 6.4% of patients.
Conclusions
In patients with symptomatic MR who were not candidates for surgery or TEER, transseptal transcatheter mitral valve replacement with the SAPIEN M3 system was associated with a significantly lower rate of death or HF rehospitalization at one year compared with the prespecified performance goal, along with very low early mortality and a sustained, near-complete reduction of mitral regurgitation.
Reference: Guerrero ME, Daniels DV, Makkar RR, Thourani VH, Asch FM, Pham M, Muhammad KI, Greenbaum AB, Vasquez A, Oldemeyer JB, Dahle TG, Rihal C, Morse MA, Rodriguez E, O’Neill BP, Russo M, Whisenant B, Yadav P, Yu X, Wang DD, Makar M, Baran DA, Mahoney P, Reddy G, Blanke P, Webb J; ENCIRCLE Trial Executive Committee and Study Investigators. Percutaneous transcatheter valve replacement in individuals with mitral regurgitation unsuitable for surgery or transcatheter edge-to-edge repair: a prospective, multicountry, single-arm trial. Lancet. 2025 Nov 29;406(10519):2541-2550. doi: 10.1016/S0140-6736(25)02073-2. Epub 2025 Oct 27. Erratum in: Lancet. 2025 Nov 29;406(10519):2540. doi: 10.1016/S0140-6736(25)02380-3. PMID: 41167201.
Subscribe to our weekly newsletter
Get the latest scientific articles on interventional cardiology
