Heart Failure
PRAISE-MR — Angiotensin Receptor Neprilysin Inhibitor in HFpEF and Secondary Mitral Regurgitation
- Authors: PRAISE-MR investigators
- Journal / date: Circulation, 2026
- DOI / URL: 10.1161/CIRCULATIONAHA.126.080833 | PMID 42104906
- Source basis: Abstract only
- Study type: Multicenter, randomized, open-label, blinded-endpoint trial
- Population: N=84 symptomatic HFpEF with ≥moderate atrial functional MR (AFMR) in the past year
- Intervention / comparator: Sacubitril/valsartan (n=41) vs standard of care (n=43), 6 months
- Primary endpoint & result: Change in exercise mPAP/CO slope on CPET-echo. Adjusted between-group difference: −0.93 mmHg/L/min (95% CI −1.80 to −0.07; p=0.035) favoring ARNI.
- Key secondary endpoints:
- Peak VO₂: +0.9 vs −0.6 mL/kg/min (p=0.002)
- KCCQ: +10 vs +2 points median (p=0.002)
- NT-proBNP and LA volume: significant reductions (p<0.001 both)
- Exercise MR augmentation: significantly blunted (p=0.020)
- Safety: Target dose achieved in 60%; symptomatic hypotension was the main titration-limiting factor.
- Why it matters (clinical takeaway):
- Suggests a phenotype-specific role for ARNI in HFpEF with AFMR — a high-risk phenotype with no proven HFpEF therapy aimed at the MR itself.
- Hemodynamic + symptom + biomarker signals are concordant, which is reassuring for a small open-label trial.
- Practically: in HFpEF patients with significant AFMR who tolerate the hypotension trade-off, sacubitril/valsartan may be worth a trial with attention to exercise dyspnea and KCCQ.
- Caveats / limitations: Open-label (blinded endpoint), N=84, single primary endpoint that is a surrogate hemodynamic measure. Needs a larger placebo-controlled outcomes trial before becoming a strong recommendation.
- Referenced trials pulled forward: PARAGON-HF (sacubitril/valsartan in HFpEF) — to add to trials/ on next pass.