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

PRECISE-AFMR I is designed to address the limited randomized evidence for transcatheter edge-to-edge repair (TEER) in patients with atrial functional mitral regurgitation (AFMR). The study uses standardized phenotypic and imaging assessment to identify patients in whom AFMR is the predominant mechanism of mitral regurgitation and whose mitral valve anatomy is considered suitable for TEER.

Before randomization, each participant will provide written informed consent and undergo clinical, laboratory, and imaging assessments. Echocardiographic data will be submitted to an independent echocardiography core laboratory (ECL) for confirmation of the AFMR diagnosis, mitral regurgitation severity, left ventricular function, left atrial remodeling, and anatomical suitability for TEER. An eligibility committee will then review the clinical findings, surgical risk, prior treatment, and ECL assessment. Only participants confirmed as eligible by both the ECL and the eligibility committee will proceed to randomization.

Eligible participants will be randomly assigned in a 1:1 ratio to TEER plus optimized guideline-directed medical therapy (GDMT) or optimized GDMT alone. Randomization will be performed through a central randomization system or electronic data capture system using blocked randomization stratified by study center or center group. The allocation sequence will be generated and maintained independently, and treatment assignment will not be released until eligibility and baseline assessments have been completed.

Because TEER is an interventional procedure, participants and treating investigators will not be blinded to treatment assignment. To reduce potential assessment bias, key echocardiographic measurements will be centrally reviewed by the ECL, and major clinical and safety events will be adjudicated by an independent clinical events committee that is blinded to treatment assignment whenever feasible. Both groups will receive comparable follow-up intensity, event collection, heart failure management, atrial fibrillation management, anticoagulation or antiplatelet therapy when clinically indicated, and management of comorbid conditions.

Participants assigned to the TEER group will undergo the procedure in addition to continued optimized GDMT and standardized clinical care. TEER is intended to be performed as soon as clinically feasible after randomization, preferably within 14 days and, when medically delayed, within 30 days whenever possible. Participants assigned to the control group will not undergo planned TEER before completion of the 12-month primary evaluation period and will receive individualized optimization of GDMT and other indicated standard treatments.

All randomized participants will be followed for 12 months, with major assessments conducted at baseline, treatment or discharge, 30 days, 6 months, and 12 months. Rescue TEER or another necessary intervention may be considered for participants in the GDMT group who experience clinically significant deterioration despite optimized treatment. Such treatment will require reassessment by the heart team, confirmation that the anticipated benefit outweighs the risk, and renewed informed consent. Rescue treatment and crossover events will be fully documented, while the primary efficacy analysis will follow the intention-to-treat principle.

Study data will be collected using standardized case report forms or an electronic data capture system. The ECL will centrally review key imaging outcomes, the clinical events committee will adjudicate major clinical and safety events, and an independent data and safety monitoring board will periodically review participant safety and study conduct.