Effects and Optimal Dose of Exercise on Endothelial Function in Patients with Heart Failure: A Systematic Review and Meta‑Analysis

Abstract

Background Exercise-based cardiac rehabilitation (CR) is considered an effective treatment for enhancing endothelial function in patients with heart failure (HF). However, recent studies have been published and the optimal “dose” of exercise required to increase the benefits of exercise-based CR programmes on endothelial function is still unknown. Objectives (a) To estimate the effect of exercise-based CR on endothelial function, assessed by flow-mediated dilation (FMD), in patients with HF; (b) to determine whether high-intensity interval training (HIIT) is better than moderate-intensity training (MIT) for improving FMD; and (c) to investigate the influence of exercise modality (i.e. resistance exercise vs. aerobic exercise and combined exercise vs. aerobic exercise) on the improvement of endothelial function. Methods Electronic searches were carried out in PubMed, Embase, and Scopus up to February 2022. Random-effects models of between-group mean differences were estimated. Heterogeneity analyses were performed by means of the chi-square test and I2 index. Subgroup analyses and meta-regressions were used to test the influence of potential moderator variables on the effect of exercise. Results We found a FMD increase of 3.09% (95% confidence interval [CI] = 2.01, 4.17) in favour of aerobic-based CR programmes compared with control groups in patients with HF and reduced ejection fraction (HFrEF). However, the results of included studies were inconsistent (p < .001; I2 = 95.2%). Higher FMD improvement was found in studies which were randomised, reported radial FMD, or performed higher number of training sessions a week. Moreover, HIIT enhanced FMD to a greater extent than MIT (2.35% [95% CI = 0.49, 4.22]) in patients with HFrEF. Insufficient data prevented pooled analyses for the effect of exercise in patients with HF and preserved ejection fraction and the influence of exercise modality on the improvement of endothelial function. Conclusion Aerobic-based CR is a non-pharmacological treatment for enhancing endothelial function in patients with HFrEF. However, higher training frequency and HIIT induce greater adaptation of endothelial function in these patients, which should betaken into consideration when designing exercise-based CR programmes. Trial registration The protocol was prospectively registered on the PROSPERO database (CRD42022304687).