Non-Pharmacological Interventions in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis

Objective : To determine the effectiveness of non-pharmacological 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-pharmacological interventions conducted in patients with HFrEF were included. Data Extraction : Data were extracted by two 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 (GRADE) method. Data Synthesis : A total of 82 eligible studies (4,574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals (CrI). High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (3.48 ml/kg∙min [2.84, 4.12]), quality of life (-17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/ml [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve quality of life. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in peak oxygen consumption, 6-minute walk distance, and quality of life. 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, 6-minute walk distance, and quality of life. Registration : PROSPERO, ID CRD42022312017.