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). Nonetheless, 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 not well-known. Objectives (a) To estimate the effect of exercise-based CR on endothelial function, assessed by flow-mediated dilation (FMD); (b) to determine whether high-intensity interval training (HIIT) is better than moderate intensity training (MIT) for improving FMD; and (c) to investigate whether there are differences between resistance exercise (alone or combined with aerobic exercise) and aerobic exercise for enhancing endothelial function. Methods Electronic searchers 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 Most of the included studies performed an aerobic-based CR programme in patients with HF and reduced ejection fraction (HFrEF). We found a FMD increase of 2.74% (95% confidence interval [CI] = 1.69, 3.79%) in favour of CR programmes compared with control groups. Nonetheless, the results of included studies were inconsistent (p < .001; I2 = 94.8%). Higher FMD improvement was found in studies performed with patients with HFrEF compared to patients with HF and preserved ejection fraction, reported radial FMD, or performed higher training frequency. Moreover, HIIT enhanced FMD to a greater extent than MIT (2.65% [95% CI = 0.98, 4.33%]), while no differences were found based on the exercise modality (1.97% [95% CI = − 0.64, 4.58%]). Conclusion Aerobic-based CR is a non-pharmacological treatment for enhancing endothelial function in patients with HFrEF. Nonetheless, training variables such as the aerobic training method (i.e., HIIT and MIT) and training frequency should be considered to properly design exercise-based CR programmes. Registration: The protocol was prospectively registered on the PROSPERO database (CRD42022304687).