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. 2025 May 14;5(3):oeaf055.
doi: 10.1093/ehjopen/oeaf055. eCollection 2025 May.

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

Konstantinos Prokopidis  1   2 , Krzysztof Irlik  3   4 , Theocharis Ispoglou  5 , Panagiotis Ferentinos  5 , Alexandros Mitropoulos  6 , Mathias Schlögl  7 , Masoud Isanejad  1 , Kamil Kegler  3 , Katarzyna Nabrdalik  2   8 , Gregory Y H Lip  2   9
Affiliations

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

Konstantinos Prokopidis et al. Eur Heart J Open. .

Abstract

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 (VO2peak), 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 VO2peak (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 VO2peak.

Conclusion: HFpEF patients demonstrated superior VO2peak, 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 VO2peak and cardiac efficiency in HFpEF.

Keywords: HFpEF; HFrEF; Heart failure; Physical function; VO2peak.

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Conflict of interest statement

Conflict of interest: None declared.

Figures

Figure 1
Figure 1
Literature search for the included studies.
Figure 2
Figure 2
Differences in six-minute walking distance between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
Figure 3
Figure 3
Differences in VO2peak between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
Figure 4
Figure 4
Differences in cardiac output between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
Figure 5
Figure 5
Differences in stroke volume between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
See this image and copyright information in PMC

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