Effect of empagliflozin with or without carvedilol on tricuspid regurgitation and right ventricular remodeling: PROVE trial.

BACKGROUND: Functional tricuspid regurgitation (TR) is associated with adverse outcomes. As TR, right ventricular (RV) remodeling, and worsening TR form a vicious cycle, therapies that reverse RV remodeling and reduce TR are needed. We examined whether sustained-release carvedilol (carvedilol SR), empagliflozin, or their combination reduces RV volumes and TR severity in patients with significant functional TR. METHODS: In this randomized trial with a 2 × 2 factorial design, 56 patients were assigned to carvedilol SR plus empagliflozin, carvedilol SR, empagliflozin, or placebo. The primary end point was the change in RV end-systolic volume index from baseline to 12 months. Secondary end points included changes in RV end-diastolic volume index, RV ejection fraction, vena contracta width (VCW), effective regurgitant orifice area (EROA), and regurgitant volume. Cardiac magnetic resonance imaging assessed RV volumes, and echocardiography evaluated TR severity. RESULTS: Baseline characteristics were well balanced between treatment groups (mean age 71 ± 7 years; men 55%; diabetes 14%; atrial fibrillation 89%). Empagliflozin did not change RV volumes or RV ejection fraction. However, empagliflozin reduced VCW (1.45 mm; 95% confidence interval [CI], 0.69-2.20), EROA (0.09 cm2; 95% CI, 0.02-0.17), and regurgitant volume (10.7 mL; 95% CI, 4.2-17.2) compared with placebo. Carvedilol SR showed no significant effect on primary or secondary end points. Compared with placebo, carvedilol SR plus empagliflozin reduced VCW (- 0.78 ± 1.15 mm vs. 0.56 ± 1.45 mm, P = 0.03) but did not change other outcomes. CONCLUSIONS: Carvedilol SR, empagliflozin, or their combination showed no significant reduction in RV volumes, but empagliflozin significantly reduced TR severity in patients with functional TR. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04345796 (PROVE trial).