Cardiopulmonary exercise testing for prognostication in heart failure with preserved ejection fraction: Meta-analysis

Background Heart failure with preserved ejection fraction (HFpEF) is associated with substantial morbidity and mortality, yet optimal risk stratification remains limited. Cardiopulmonary exercise testing (CPET) offers integrated physiologic assessment, but its prognostic role in HFpEF is not well established. Methods We conducted a systematic review and meta-analysis of observational studies evaluating the prognostic value of CPET parameters in HFpEF. Databases were searched through March 2026. Primary outcomes included all-cause mortality, heart failure (HF) hospitalization, and composite cardiac events. Pooled event rates were estimated using random-effects generalized linear mixed models, and hazard ratios (HRs) were synthesized using inverse-variance random-effects models. Results Eight studies including 1397 patients were analyzed. The pooled incidence of all-cause mortality was 11.7% (95% CI 6.9–19.1), HF hospitalization 21.5% (95% CI 12.2–35.1), and composite cardiac events 15.9% (95% CI 10.5–23.2). Higher VE/VCO₂ slope was significantly associated with increased risk of composite cardiac events (HR 1.12, 95% CI 1.06–1.17) and showed a borderline association with mortality (HR 1.04, 95% CI 1.00–1.08). Peak VO₂ was not significantly associated with outcomes, with substantial heterogeneity observed. Conclusions In HFpEF, VE/VCO₂ slope is associated with an increased risk of composite cardiac events, supporting its role in risk stratification. Peak VO₂ showed inconsistent prognostic value, likely reflecting population and methodological heterogeneity. Larger prospective studies are needed to refine CPET-based risk models in HFpEF. PROSPERO registration CRD420261374935.