PRECISE-AFMR I: Transcatheter Mitral Valve Edge-to-Edge Repair for Atrial Functional Mitral Regurgitation in Patients at High Surgical Risk

Atrial functional mitral regurgitation (AFMR) develops when enlargement and remodeling of the left atrium and mitral annulus prevent the mitral valve leaflets from closing completely, allowing blood to leak backward through the valve. For patients with significant AFMR who remain symptomatic despite medical treatment and are at high risk for surgery, it is uncertain whether adding transcatheter mitral valve edge-to-edge repair (TEER), a catheter-based procedure that brings the mitral valve leaflets together, provides better outcomes than medical treatment alone. PRECISE-AFMR I is a prospective, multicenter, randomized study that will enroll 182 adults with moderate-to-severe or severe AFMR, high or prohibitive surgical risk, and mitral valve anatomy suitable for TEER. Participants will be assigned in a 1:1 ratio to receive TEER plus optimized guideline-directed medical therapy (GDMT) or optimized GDMT alone. All participants will receive standardized medical care and will be followed for 12 months. The main effectiveness outcome is the occurrence of death from any cause or hospitalization for heart failure within 12 months. The main safety outcome is the occurrence of major device-related adverse events within 12 months. The study will also assess mitral regurgitation severity, symptoms, functional capacity, quality of life, heart failure events, and use of health care resources.

Inclusion Criteria: * 1\. Aged ≥18 years; 2\. Presence of symptoms of heart failure, with New York Heart Association (NYHA) functional class II, III, or ambulatory class IV; 3\. Confirmed by preliminary assessment of the study-site Heart Team and review by the Echocardiography Core Laboratory (ECL) to have at least moderate-to-severe atrial functional mitral regurgitation (AFMR), generally graded as 3+ or 4+; 4\. At least one hospitalization for heart failure within the 12 months prior to enrollment and/or a plasma B-type natriuretic peptide (BNP) level ≥300 pg/mL or N-terminal pro-B-type natriuretic peptide (NT-proBNP) level ≥1,500 pg/mL; 5\. As confirmed by a heart failure specialist at the study site, the subject has received maximally optimized guideline-directed medical therapy (GDMT) and other necessary standardized comprehensive treatment in accordance with current guidelines for at least 3 months. For subjects with concomitant atrial fibrillation, coronary artery disease, or other potentially correctable comorbidities, appropriate evaluation and guideline-recommended management must have been completed, or the subject must have been clearly determined to be unsuitable for further treatment; 6\. Determined by the multidisciplinary Heart Team, in accordance with the process described in Section 4.7, to be at high surgical risk, to have a contraindication to surgery, or to be unsuitable for surgery, or determined after comprehensive assessment that surgical treatment is not the optimal current strategy; 7\. During the screening period or within 90 days prior to randomization, mitral valve anatomy is assessed by echocardiography at the study site and confirmed by the ECL to be suitable for transcatheter edge-to-edge repair (TEER). Anatomical suitability must meet at least all of the following criteria: * Mitral valve area \>4.0 cm² and baseline mean transmitral pressure gradient \