Unraveling Heart Failure Phenotypes: A Systematic Review and Meta-analysis of Peak Oxygen Uptake and Its Determinants

Abstract

Background

Understanding the impact of heart failure (HF) phenotype on peak oxygen uptake (peak $\dot{V}$O₂) is essential for advancing personalized treatment strategies and enhancing patient outcomes. Therefore, we conducted a systematic review and meta-analysis of the evidence examining differences in peak $\dot{V}$O₂ (primary objective) and its determinants (secondary objectives) between patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF).

Methods

Studies comparing peak $\dot{V}$O₂ in HFrEF vs HFpEF were found through PubMed (1967-2024), Scopus (1981-2024), and Web of Science (1985-2024). Data extraction and methodologic quality assessment were completed by 2 independent coders. Differences between HFrEF and HFpEF were compared using weighted mean difference (WMD) and 95% confidence intervals (95% CIs) derived from random effects meta-analysis.

Results

After screening 3107 articles, 25 unique studies were included in the analysis for the primary outcome (HFrEF n = 3783; HFpEF n = 3279). Peak $\dot{V}$O₂ (WMD: –1.6 mL/kg/min, 95% CI: –2.3 to –0.8 mL/kg/min), and peak exercise measures of cardiac output (WMD: –1.1 L/min, 95% CI: –2.1 to –0.2 L/min), stroke volume (WMD: –10.1 mL, 95% CI: –16.6 to –3.7 mL), heart rate (WMD: –4 bpm, 95% CI: –6 to –2 bpm), and left ventricular ejection fraction (WMD: –28.2%, 95% CI: –32.6% to –23.8%) were significantly lower while peak exercise arterial-venous oxygen difference was significantly higher in HFrEF compared with HFpEF (2.3 mL/dL, 95% CI: 1.6-2.9 mL/dL).

Conclusions

Our findings highlight distinct physiological impairments along the oxygen cascade in HFrEF compared with HFpEF, with direct implications for the management and treatment strategies of these HF subtypes.