PURPOSE: Given that previous reviews on exercise training in pulmonary hypertension (PH) were largely based on a small number of randomized controlled trials (RCT), their conclusions are subject to bias. This review sought to identify the impact of exercise training on functional capacity and health-related quality of life (HRQoL) in PH using advanced statistical approaches such as meta-analysis by stratification according to study design. REVIEW METHODS: Five databases were searched from January 2015 to April 2020 to update a previous review. Included articles had data extracted, risk of bias (ROB) assessed, and quality rating performed. Data were analyzed using meta-analysis with a random-effects model for 6-min walk test (6MWT) distance and HRQoL. Heterogeneity was explored using stratified meta-analysis, within patient correlation and meta-regression. RESULTS: A total of 28 studies (11 RCT, 12 pre-/post-studies, 2 two-group non-RCT, and three case series) consisting of 1264 patients were included. Meta-analysis of six RCT demonstrated an improved 6MWT distance by 49.5 m (95% CI 27.2 to 71.8, I2 73%, 254 participants, low-moderate ROB) with a low correlation coefficient of 0.34, while the 12 pre-/post-non-RCT showed an improvement of 68.69m (95% CI 50.50 to 86.69, I2 36%, 784 participants, high ROB) along with improvements in Vo2peak (weighted mean difference (WMD) 3.03 mL/kg/min, 95% CI 2.17 to 3.90, I2 0%, p = 0.82), and HRQoL (WMD 2.74, 95% CI -0.82 to 6.30). Metaregression showed that the benefit of exercise on 6MWT distance did not significantly vary across the trial study characteristics. CONCLUSION: This updated review identified an additional body of evidence supporting the efficacy of exercise training on 6MWT distance and HRQoL in stable PH patients. These benefits appeared to be consistent across models of delivery.
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