Exercise Training for Heart Failure With Preserved Ejection Fraction (ExTraMATCH III): Protocol for an Individual Patient Data Meta-Analysis

Background: We will undertake an individual patient data (IPD) meta-analysis to assess the impact of exercise-based cardiac rehabilitation in patients with heart failure with preserved ejection fraction (HFpEF) on mortality and hospitalization and quality of life of exercise-based cardiac rehabilitation according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischemic etiology, ejection fraction, and exercise capacity. Despite emerging evidence supporting exercise training in HFpEF, uncertainties remain in the interpretation and understanding of this evidence base. Clinicians and health care providers seek definitive estimates of impact on mortality, hospitalization and health-related quality of life (HRQoL). This work is, therefore, important as HFpEF treatment options are evolving; however, efficacy of some medications is equivocal, so optimizing exercise rehabilitation is vital. Methods: We conducted a systematic search to identify randomized trials of exercise training for at least 3 weeks compared with no exercise control with 6-month follow up or longer, providing IPD time to event on mortality or hospitalization (all-cause or heart failure-specific). IPD will be combined into a single dataset. We will use Cox proportional hazards models to investigate the effect of exercise-based cardiac rehabilitation and the interactions between exercise-based cardiac rehabilitation and participant characteristics. We will use a mix of one-stage and two-stage models. Original IPD will be requested from the authors of all eligible trials; we will check original data and compile a master dataset. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modeled simultaneously while accounting for the clustering of participants with studies. Results: We expect our analyses to show improved mortality, hospitalization, cardiorespiratory fitness, and health-related quality of life. Conclusion: This work will clarify exercise-based rehabilitation delivery methods to optimize benefits for people with HFpEF.