Background:
Heart failure with preserved ejection fraction (HFpEF) is a progressive condition associated with high hospitalization and mortality rates. Exercise intolerance, chronotropic incompetence, elevated resting heart rate, and diastolic dysfunction are key prognostic markers. This systematic review and meta-analysis evaluated the effects of pharmaceutical and physical therapies on exercise capacity, chronotropic response, and left ventricular filling pressure (LVFP) in individuals with HFpEF.
Methods:
We conducted a systematic search of PubMed, Medline, the Clinical Trials Register, and Cochrane Central from inception to June 8, 2024. We included randomized controlled trials (RCTs) involving adults with HFpEF that reported peak oxygen consumption (VO2peak) as the primary outcome, with secondary outcomes including resting and peak heart rate and rest E/e′. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool for pharmaceutical studies and the Tool for the Assessment of Study Quality and Reporting in Exercise scale for physical therapy studies. Data were synthesized using a random-effects model in Review Manager 5.4.1.
Results:
Twenty-one studies (N = 2,491 participants) met inclusion criteria; 14 were included in the meta-analysis (pharmaceutical [n = 10], physical [n = 4]). Physical therapy significantly improved VO₂peak (mean difference [MD] 2.33 mL·kg‾¹·min‾¹; 95% confidence interval [95% CI], 1.71–2.95 mL·kg‾¹·min‾¹; P < 0.00001; I² = 0%) and increased peak heart rate [HR] (MD, 9.78 b·min‾¹; 95% CI, 3.93–15.63 b·min‾¹; P = 0.001; I² = 39%). Pharmaceutical therapies showed no significant pooled effects overall. Subgroup analyses showed β-blockers and phosphodiesterase inhibitors reduced peak HR; mineralocorticoid receptor antagonists increased peak HR and reduced rest E/e′. The evidence base is limited by small sample sizes and heterogeneity across interventions and study populations. Sparse data prevented broader comparisons.
Conclusion:
Current evidence suggests that exercise-based physical therapies may improve exercise capacity and chronotropic response in HFpEF, and mineralocorticoid receptor antagonists may reduce LVFP. Heart rate–lowering therapies do not appear to impair exercise capacity. However, because of generally low to moderate certainty of evidence, these findings should be interpreted cautiously. Further high-quality, standardized RCTs are needed to confirm these effects and guide clinical practice.
Registration:
Registered with PROSPERO (CRD42024556709).
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)