OBJECTIVE: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023. STUDY SELECTION: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method. DATA SYNTHESIS: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6 minute walk distance (6MWD 68.55 m (36.41 to 100.47)) and left ventricular ejection fraction (6.28% (3.88 to 8.77)), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO2 3.48 mL/kg/min (2.84 to 4.12)), quality of life (QOL; -17.26 (-29.99 to -7.80)), resting heart rate (-8.20 bpm (-13.32 to -3.05)), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL (-902.93 to -404.52)). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO2, 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events. CONCLUSIONS: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL.

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