Sacubitril/Valsartan Improves Exercise Capacity in HFpEF with Mitral Regurgitation
The PRAISE-MR trial finds sacubitril/valsartan significantly improves exercise hemodynamics and quality of life in a high-risk HFpEF phenotype.
Summary
The PRAISE-MR trial randomized 84 patients with heart failure with preserved ejection fraction (HFpEF) and significant mitral regurgitation to sacubitril/valsartan or standard care. After six months, the sacubitril/valsartan group showed meaningful improvements in exercise hemodynamics, peak oxygen consumption, and quality-of-life scores. The drug also reduced NT-proBNP, shrank left atrial volume, and blunted the worsening of mitral regurgitation that typically occurs during exercise. Symptomatic low blood pressure was the main barrier to reaching target doses. These results suggest sacubitril/valsartan may offer particular benefit for this specific HFpEF subgroup, though larger placebo-controlled trials are needed to confirm clinical outcomes.
Detailed Summary
Heart failure with preserved ejection fraction (HFpEF) is notoriously difficult to treat, and the presence of atrial functional mitral regurgitation (AFMR) makes the prognosis even worse. Finding therapies that address both the hemodynamic burden and the valve dysfunction in this phenotype is a major clinical priority.
The PRAISE-MR trial enrolled 84 patients across multiple centers in Belgium. All had symptomatic HFpEF and at least moderate AFMR. Participants were randomly assigned to sacubitril/valsartan — a combined angiotensin receptor neprilysin inhibitor — or standard-of-care therapy. The primary endpoint was the six-month change in the exercise pulmonary arterial pressure-to-cardiac output slope, measured using a sophisticated combination of cardiopulmonary exercise testing and simultaneous echocardiography.
Sacubitril/valsartan significantly improved the hemodynamic slope compared to standard care, reflecting better cardiac efficiency under stress. Peak VO2 increased by nearly 1 mL/kg/min in the treatment group while declining in controls. Kansas City Cardiomyopathy Questionnaire scores rose by a clinically meaningful 10 points versus just 2 in the control arm. NT-proBNP and left atrial volume fell substantially, and the exercise-induced surge in mitral regurgitation severity was significantly blunted.
These findings point to a phenotype-specific benefit: sacubitril/valsartan appears to simultaneously improve cardiac mechanics, reduce filling pressures, and stabilize the mitral valve apparatus during physical stress — a combination that no prior therapy has demonstrated in this patient group.
Caveats are important. The trial was open-label and relatively small at 84 patients. Only 60% of participants achieved target drug dosing due to hypotension. The summary is based on the abstract only, and full data including subgroup analyses and adverse event profiles are not yet available. Confirmation in a larger, placebo-controlled, outcomes-driven trial is essential before this becomes standard practice.
Key Findings
- Sacubitril/valsartan improved the exercise pulmonary pressure-to-cardiac output slope by 0.93 mmHg/L/min versus standard care.
- Peak VO2 rose ~1.5 mL/kg/min more in the treatment group compared to controls over 6 months.
- Quality-of-life scores (KCCQ) improved 10 points with sacubitril/valsartan vs. 2 points with standard care.
- Exercise-induced worsening of mitral regurgitation was significantly blunted in the sacubitril/valsartan group.
- NT-proBNP and left atrial volume both fell significantly, signaling reduced cardiac stress.
Methodology
Multicenter, randomized, open-label trial with blinded primary endpoint assessment across Belgian cardiology centers. Eighty-four patients with HFpEF and at least moderate AFMR were assigned to sacubitril/valsartan or standard-of-care for 6 months. The primary endpoint used cardiopulmonary exercise testing combined with simultaneous echocardiography, a rigorous and novel hemodynamic assessment approach.
Study Limitations
The trial was open-label and small (n=84), limiting generalizability and increasing risk of performance bias. Only 60% of patients achieved target sacubitril/valsartan dosing due to hypotension, which may underestimate the true treatment effect. Critically, this summary is based on the abstract only, as the full manuscript was not accessible.
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