Exercise capacity in heart failure: a systematic review and meta-analysis of HFrEF and HFpEF disparities in VO2peak and 6-minute walking distance.

Aims: Heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) exhibit unique physiological pathways, influencing exercise capacity and functional performance. This systematic review and meta-analysis aimed to compare peak oxygen consumption (VO_2peak), six-minute walk distance (6MWD), cardiac output (CO), and stroke volume (SV), between these phenotypes.

Methods and results: A systematic literature search of cohort studies via databases (PubMed, Web of Science, Scopus, and Cochrane Library) was conducted from inception until October 2024. A meta-analysis using a random-effects model to calculate the pooled effects was employed. Forty-six studies were included. HFrEF patients demonstrated significantly greater 6MWD compared to HFpEF (k = 20; mean difference (MD): 18.09 m, 95% confidence interval (CI) 1.59-34.59, I² = 86%, P = 0.03), though this difference became insignificant after adjusting for comorbidities. Conversely, HFpEF patients exhibited higher VO_2peak (k = 20; MD: -0.78 mL/kg/min, 95% CI -1.45--0.11, I² = 89%, P = 0.02), CO (k = 12; MD: -1.15 L/min, 95% CI -2.11--0.19, I² = 97%, P = 0.02), and SV (k = 14; SMD: -1.00, 95% CI -1.60--0.39, I² = 95%, P < 0.01). Age was identified as a significant moderator of VO_2peak.

Conclusion: HFpEF patients demonstrated superior VO_2peak, CO, and SV compared to HFrEF patients, while the observed 6MWD advantage in HFrEF was likely influenced by comorbidities. Our findings emphasize the importance of tailoring rehabilitation strategies to HF phenotype-specific physiological profiles, particularly focusing on improving VO_2peak and cardiac efficiency in HFpEF.