The Impact of β-Blocker Therapy on Peak VO2 in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for over half of all heart failure cases and remains without definitive therapy. β-blockers (BB) are frequently prescribed, often extrapolated from HFrEF management, but their benefit in HFpEF is uncertain. By reducing heart rate and contractility, BB may further limit exercise capacity in patients whose cardiac output is rate-dependent. PURPOSE: To systematically evaluate the impact of BB therapy on functional capacity, quality of life, and natriuretic peptide levels in patients with HFpEF. METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO CRD420251229202). PubMed, Embase, and Cochrane databases were searched through November 2025 for randomized and observational studies assessing BB therapy or withdrawal in HFpEF. The primary end point was peak oxygen consumption (VO2 peak). Secondary outcomes included Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Mean or standardized mean differences (95% CI) were pooled using a random-effects model. RESULTS: Five studies comprising 803 patients (525 on BB therapy) were included. BB use was associated with a significant reduction in VO2 peak (MD = -2.02 mL·kg⁻1·min⁻1; 95% CI -3.26 to -0.79; p < 0.01). No significant differences were found in MLHFQ scores (SMD = 0.32; 95% CI -0.57 to 1.21; p = 0.48) or NT-proBNP levels (MD = 130.71 pg/mL; 95% CI -143.27 to 404.69; p = 0.35). CONCLUSIONS: BB therapy was associated with lower objective peak VO2 without consistent effects on patient-reported outcomes or natriuretic peptides. TRIAL REGISTRY: Prospero registration: CRD420251229202.