Effects of exercise training on cardiac output in subjects with heart failure with preserved ejection fraction (HFpEF) – a protocol for a systematic review and meta-analysis

Abstract

Background: Patients with heart failure with preserved ejection fraction (HFpEF) commonly experience exercise intolerance, resulting in reduced cardiorespiratory fitness. This is characterised by a decreased maximal oxygen uptake (V̇O_2peak), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO₂). While exercise training has been shown to improve V̇O_2peak in HFpEF patients, the effects on CO remain unclear. The aim of this study is to systematically review and analyse the current evidence on the effects of supervised exercise training on CO in patients with HFpEF. Methods: We will systematically search for literature describing the effects of supervised exercise training on CO in patients with HFpEF. All eligible studies published before 30 June 2023 in the following electronic databases will be included: Medline (Ovid), Embase (Ovid), SportDiscus (EBSCOhost), and CENTRAL (Cochrane Library). Effect sizes will be extracted for CO before and after a supervised exercise training intervention at rest and maximal exercise. Mass of heterogeneity (I²) will be calculated and either fixed effect models or random effect models will be used for meta-analysis. To detect a potential publication bias, funnel plot analyses will be performed. Discussion: While several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O_2peak, CO, and a-vDO₂ are much scarcer, especially in patients with HFpEF. From a physiological perspective, measuring CO before and after supervised exercise training seems to be a reasonable way to accurately operationalise a potential improvement in cardiac function. PROSPERO registration number CRD42022361485.