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Clinical Trial
. 2025 Nov 29;406(10519):2541-2550.
doi: 10.1016/S0140-6736(25)02073-2. Epub 2025 Oct 27.

Percutaneous transcatheter valve replacement in individuals with mitral regurgitation unsuitable for surgery or transcatheter edge-to-edge repair: a prospective, multicountry, single-arm trial

Mayra E Guerrero  1 , David V Daniels  2 , Raj R Makkar  3 , Vinod H Thourani  4 , Federico M Asch  5 , Michael Pham  6 , Kamran I Muhammad  7 , Adam B Greenbaum  8 , Alejandro Vasquez  9 , J Bradley Oldemeyer  10 , Thom G Dahle  11 , Charanjit Rihal  12 , M Andrew Morse  13 , Evelio Rodriguez  14 , Brian P O'Neill  15 , Mark Russo  16 , Brian Whisenant  17 , Pradeep Yadav  18 , Xiao Yu  19 , Dee Dee Wang  20 , Moody Makar  21 , David A Baran  22 , Paul Mahoney  23 , Gautam Reddy  9 , Philipp Blanke  24 , John Webb  25 ; ENCIRCLE Trial Executive Committee and Study Investigators
Collaborators, Affiliations
Clinical Trial

Percutaneous transcatheter valve replacement in individuals with mitral regurgitation unsuitable for surgery or transcatheter edge-to-edge repair: a prospective, multicountry, single-arm trial

Mayra E Guerrero et al. Lancet. .

Erratum in

  • Department of Error.
    [No authors listed] [No authors listed] Lancet. 2025 Nov 29;406(10519):2540. doi: 10.1016/S0140-6736(25)02380-3. Lancet. 2025. PMID: 41318213 No abstract available.

Abstract

Background: Patients with severe mitral regurgitation are frequently not candidates for surgery or transcatheter edge-to-edge repair (TEER). We aimed to evaluate 1-year outcomes of a novel percutaneous transseptal transcatheter mitral valve replacement (TMVR) system in patients unsuitable for surgery or TEER.

Methods: In this prospective, multicentre, single-arm, pivotal trial, adult patients (aged ≥18 years) with symptomatic moderate-to-severe or severe mitral regurgitation who were not suitable for surgery or TEER were recruited at 56 centres in six countries (the USA, Canada, the UK, the Netherlands, Israel, and Australia). Eligible patients were treated with TMVR using the SAPIEN M3 system (Edwards Lifesciences, Irvine, CA, USA). The primary endpoint was a non-hierarchical composite of all-cause mortality and heart failure rehospitalisation at 1 year in the as-treated population, compared with a prespecified performance goal of 45%. This trial is registered with ClinicalTrials.gov, NCT04153292, and is ongoing.

Findings: Between June 9, 2020, and Oct 10, 2023, 1171 patients were screened, of whom 299 were treated. Follow-up data were available for 283 (95%) patients at 30 days and 243 (81%) at 1 year (median follow-up 1·4 years [IQR 1·0-2·1]). The median age was 77·0 years (IQR 70·0-82·0), 152 (51%) participants self-reported as male and 147 (49%) as female, and the mean Society of Thoracic Surgeons predicted risk of 30-day mortality for mitral valve replacement was 6·6%. There were no intraprocedural deaths, no instances of left ventricular outflow tract obstruction causing haemodynamic compromise, and no conversions to surgery. The primary endpoint rate of 25·2% (95% CI 20·6-30·6) was significantly lower than the prespecified performance goal of 45% (p<0·0001).

Interpretation: Percutaneous transseptal TMVR with the SAPIEN M3 system effectively reduced mitral regurgitation with low rates of complications and mortality. These findings support percutaneous TMVR with the SAPIEN M3 system as a therapeutic option for patients who are unsuitable for surgery or TEER.

Funding: Edwards Lifesciences.

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Conflict of interest statement

Declaration of interests MEG reports institutional research grant support from Edwards Lifesciences. DD reports acting as a consultant and proctor for Edwards Lifesciences. RRM reports research grants and travel support from Edwards Lifesciences, Abbott, Boston Scientific, Medtronic, and JenaValve; and equity in and being an advisor for iCardio. VT reports consultancy and research for Edwards Lifesciences. FMA reports directing an institutional academic core laboratory with MedStar Health; and research grants or contracts with Edwards Lifesciences, Abbott, Boston Scientific, Medtronic, Ancora Heart, Neovasc, Johnson & Johnson, InnovHeart, Polares Medical, InterShunt, TRiCares, Xeltis, Foldax, CroiValve, VDyne, Us2.ai, Ultromics, MyCardium, GE, TOMTEC, and egnite. MP reports author royalties for up-to-date topics related to heart transplantation, not related to the current work. KM reports acting as a consultant and proctor for Edwards Lifesciences, Medtronic, and Abbott; and consultancy for Ancora Heart and Emboline. AG reports acting as a consultant and proctor for Edwards Lifesciences. AV reports consultancy for Edwards Lifesciences and Atrion Medical. JBO reports acting as a proctor for Edwards Lifesciences. TD reports acting as a consultant and proctor for Edwards Lifesciences. CR reports institutional research grant support from Edwards Lifesciences. MAM reports participation in the speakers bureau for physician training for Edwards Lifesciences. ER reports consultancy for and research-related payments from Abbott, Edwards Lifesciences, Medtronic, AtriCure, 3ive Labs, and Boston Scientific. BPO reports consultancy for Edwards Lifesciences. MR reports acting as a speaker and consultant for Edwards Lifesciences and Abbott; and being a site principal investigator for Edwards Lifesciences, Abbott, and Jena. BW reports acting as a consultant and proctor for Edwards Lifesciences. PY reports acting as a consultant and speaker for Edwards Lifesciences, Abbott, and Boston Scientific; and participation on advisory boards with stock options for DASI Simulations, Trisol, Pi-Cardia, TRiCare, and Excision Medical. XY reports employment by Edwards Lifesciences. DDW reports consultancy for Edwards Lifesciences and Abbott. MAM reports consultancy for Abbott Vascular, Boston Scientific, Edwards Lifesciences, and GE HealthCare. DAB reports paid consultancy for Envello; participation on steering committees for CareDx and Natera; and participation on data and safety monitoring boards for XVIVO, the PACCS trial, and the MAGENTA Elevate trial. PM reports consultancy for Edwards Lifesciences, Medtronic, and Abbott. PB reports consultancy and provision of institutional cardiac CT core laboratory service for Edwards Lifesciences without direct personal compensation. JW reports consultancy for Edwards Lifesciences. GR declares no competing interests.

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