Abstract
BACKGROUND AND AIMS: Heart failure (HF) is a multifactorial disease for which peak oxygen uptake (VO(2)peak) may potentially be a prognostic marker of adverse clinical outcomes. This systematic review and meta-analysis aimed to assess published data on the prognostic impact of VO(2)peak in HF. METHODS: A literature search of observational studies was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until January 2025. A meta-analysis was conducted using the random-effects inverse-variance model through hazard ratios (HRs). Increased heterogeneity among studies was evaluated through meta-regressions and publication bias via Egger's test. RESULTS: Sixty-four studies were included in this systematic review and meta-analysis. Per 1 mL/kg/min increase in VO(2)peak, all-cause mortality [HR: 0.86, 95% confidence interval (CI) 0.82-0.90, I(2) = 85%, P < 0.01] and incident ventricular assist device, transplant and all-cause mortality (HR: 0.84, 95% CI 0.79-0.89, I(2) = 33%, P < 0.01) were significantly reduced, but statistical significance of VO(2)peak with cardiovascular mortality was not observed (HR: 0.92, 95% CI 0.82-1.02, I(2) = 0%, P = 0.12) using adjusted models. Variance among studies was detected based on age, sex, body mass index, left ventricular ejection fraction, atrial fibrillation, hypertension, chronic kidney disease, diabetes and treatment. A significant risk of publication bias was evident. CONCLUSIONS: VO(2)peak is a prognostic marker for multiple causes of mortality and hospitalization in patients with HF, which may promote further insights into patient risk stratification for adverse events and targeted management.