PRAISE-MR is the first medical-therapy trial demonstrating exercise-hemodynamic benefit in HFpEF with atrial functional mitral regurgitation (AFMR). In 84 patients randomized to sacubitril-valsartan or standard of care, the 6-month change in exercise mPAP/CO slope improved by 0.93 mmHg/L/min with sacubitril-valsartan (95% CI 0.07–1.80; p=0.035). Peak VO2, KCCQ score, NT-proBNP, LA volume and AFMR severity all improved. The findings position ARNI as a credible disease-modifying option for HFpEF + AFMR, alongside transcatheter mitral repair as evidence emerges.
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.
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.
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.
In symptomatic HFpEF with secondary AFMR, sacubitril/valsartan improved exercise hemodynamics, exercise capacity, quality of life, and biomarker and structural endpoints over six months.
