Determining the effect size of structured and unstructured physical activity on clinical outcomes associated with adult and adolescent congenital heart conditions: protocol for a systematic review with multivariate meta-analysis and meta-regression of randomised controlled trials

Objectives To determine the effect size of physical activity on clinical outcomes of a cohort comprising adults and adolescents with congenital heart (CH) conditions and examine change in outcomes arising from study or intervention covariates. Design Systematic review and multivariate meta-analysis and meta-regression of randomised controlled trials (RCTs). Data sources Searches of PubMed, CINAHL, SPORTDiscus, EMBASE and Web of Science from inception to June 30, 2024. Eligibility criteria We will include published RCTs of CH adolescents (> 16 years) and adults with ≥ 10 participants, an intervention duration ≥ 6 weeks, intensity > 40% maximal oxygen consumption or > 6 OMNI-RES Scale or equivalent, and reporting pre-/post-measurements. Trials of subjects with other chronic disease, pregnant/lactating, or testing diet modification or medications concurrently, will be excluded. Results We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statements. Multivariate meta-analyses will be performed to investigate the effects of physical activity interventions on independent and correlated physiological and psychological outcomes, and use a random mean difference, Knapp-Hartung adjusted, 95% confidence interval, meta-analysis model. Heterogeneity will be evaluated using fail-safe N, rank correlation, trim-and-fill, regression tests, and precision and standard error funnel plots. Multivariate meta-regression will explore whether study or intervention variables explain change in outcomes. Analyses will be performed in Comprehensive Meta-Analysis 4.0. Study quality will be evaluated using TESTEX and the Cochrane Risk of Bias assessment. Discussion We aim to determine the impact of different modes of structured and unstructured exercise protocols on clinical outcomes of adults and adolescents diagnosed with CH conditions and identify any covariates that might explain changes in these outcomes. Systematic review registration PROSPERO CRD42023400406.