In patients with atrial functional mitral regurgitation (AFMR) and heart failure with reduced ejection fraction (HFpEF), sacubitril/valsartan was associated with improvements in exercise hemodynamics and peak oxygen consumption (VO₂), along with attenuation of an exercised-induced increase in AFMR, according to results from the PRAISE-MR study published May 9 in Circulation.

In their open-label, blinded primary endpoint trial, Sebastiaan Dhont, MD, et al., randomized 84 patients ≥40 years old diagnosed with symptomatic HFpEF and ≥moderate AFMR within the previous year to either sacubitril/valsartan (n=41) or standard of care (SOC) (n=43). Data were collected from February 29, 2024, through September 24, 2025, at two centers in Belgium.

Researchers defined the primary outcome as the six-month change in exercise mean pulmonary arterial pressure to cardiac output slope (mPAP/CO), which was assessed using cardiopulmonary exercise testing with simultaneous echocardiography (CPETecho). Secondary outcomes were changes in peak (VO₂), NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire (KCCQ), left atrial (LA) volume and function and AFMR severity in rest and during stress.

At six-month follow-up, treatment with sacubitril/valsartan significantly improved the mPAP/CO slope when compared with SOC (adjusted between-group difference: −0.93 mm Hg/L/min; 95% CI, −1.80 to −0.07; p=0.035). This hemodynamic improvement was accompanied by a significant increase 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).

Additionally, significant reductions were observed in NT-proBNP levels and LA volume, as well as significant blunting of the dynamic MR increase during exercise. The target dose was achieved in 60% of patients, with symptomatic hypotension representing the primary titration-limiting factor.

"The PRAISE-MR trial is the first prospectively randomized trial to demonstrate that sacubitril/valsartan significantly improves exercise hemodynamics, functional capacity, and quality of life in patients with HFpEF and AFMR," write the authors. "These findings underscore that the phenotypic heterogeneity of HFpEF necessitates a more targeted therapeutic approach."