Transcatheter edge-to-edge repair in dynamic severe functional mitral regurgitation: A multicentre, randomised, controlled trial

Abstract Background Functional mitral regurgitation (FMR) is a highly dynamic disease. Some patients exhibit only moderate (2+) FMR at rest, which deteriorates to moderate-to-severe or severe FMR (3+ or 4+) during stress, with effective regurgitant orifice area (EROA) increased ≥0.1 cm2—termed dynamic severe FMR. Observational studies link this condition to worse outcomes, with mitral valve intervention offering potential benefits; however, high-quality evidence remains deficient. Aims The Transcatheter edge-to-edge repair In dynaMic sEvere functional mitral Regurgitation (TIMER) trial aims to assess the safety and effectiveness of transcatheter edge-to-edge repair plus guideline-directed medical therapy versus guideline-directed medical therapy alone in symptomatic chronic heart failure patients with dynamic severe FMR, defined as moderate (2+) regurgitation at rest (EROA ≥0.2 cm2 to <0.3 cm2 and/or regurgitant volume (RVol) ≥30 mL/beat to <45 mL/beat), deteriorating to moderate-to-severe or severe (3+ or 4+) during handgrip stress echocardiography (stress EROA ≥0.30 cm2 and/or RVol ≥45 mL/beat), with EROA increased ≥0.1 cm2. Methods This prospective, multicentre, randomised trial enrols patients with dynamic severe FMR confirmed by a core laboratory using handgrip stress echocardiography, across 20 participating centres in China. Patients are randomised 1:1 to transcatheter edge-to-edge repair plus medical therapy or medical therapy alone. The primary endpoint is the composite incidence of cardiovascular death and all heart failure hospitalisations during the entire follow-up period. Conclusion This trial will provide critical evidence on transcatheter edge-to-edge repair in patients with dynamic severe FMR, informing future treatment recommendations. Trial registration number: NCT07197021