PRAISE-MR: sacubitril-valsartan verbetert inspanningshemodynamiek bij HFpEF met atriale mitralisinsufficiëntie

Background: Atrial functional mitral regurgitation (AFMR) characterizes a high-risk phenotype in heart failure with preserved ejection fraction (HFpEF). Although sacubitril/valsartan reduces functional MR in HF with reduced EF (HFrEF), its impact on exercise hemodynamics and the dynamic burden of AFMR in HFpEF remains to be elucidated. Methods: This multicenter, randomized, open-label trial with blinded primary endpoint assessment assigned 84 patients with symptomatic HFpEF and ≥moderate AFMR within the previous year to sacubitril/valsartan (n=41) or standard-of-care (SOC; n=43). The primary outcome was the 6-month change in the exercise mean pulmonary arterial pressure to cardiac output (mPAP/CO) slope, assessed using cardiopulmonary exercise testing with simultaneous echocardiography (CPETecho). Secondary outcomes included changes in peak oxygen consumption (peak VO2), Kansas City Cardiomyopathy Questionnaire (KCCQ), NT-proBNP levels, LA volume and function, and AFMR severity in rest and during stress. Results: At 6 months, sacubitril/valsartan significantly improved the mPAP/CO slope compared to SOC (adjusted between-group difference in change: -0.93 mmHg/L/min; 95%CI: -1.80 to -0.07; p=0.035). This hemodynamic benefit was accompanied by improvements in peak VO2 (+0.9 vs. -0.6 mL/kg/min; p=0.002) and KCCQ (median increase: 10 vs. 2 points; p=0.002). Significant reductions in NT-proBNP and LA volume were observed, alongside attenuation of AFMR severity at rest and during exercise. Conclusions: In symptomatic HFpEF with secondary AFMR, sacubitril/valsartan improved exercise hemodynamics, exercise capacity, quality of life, and biomarker and structural endpoints over six months.