Targeting Ketone Body Metabolism Improves Cardiac Function and Hemodynamics in Patients With Heart Failure: A Systematic Review and Meta-Analysis

Abstract Context The impacts of elevated ketone body levels on cardiac function and hemodynamics in patients with heart failure (HF) remain unclear. Objective The effects of ketone intervention on these parameters in patients with HF were evaluated quantitatively in this meta-analysis. Data Sources We searched the PubMed, Cochrane Library, and Embase databases for relevant studies published from inception to April 13, 2024. Ketone therapy included ketone ester and β-hydroxybutyrate intervention. Data Extraction Seven human studies were included for the quantitative analysis. Data Analysis Our results showed that ketone therapy significantly improved left ventricular ejection fraction (standardized mean difference, 0.52 [95% CI, 0.25-0.80]; I2 = 0%), cardiac output (0.84 [95% CI, 0.36-1.32]; I2 = 68%) and stroke volume (0.47 [95% CI, 0.10-0.84]; I2 = 39%), and significantly reduced systemic vascular resistance (–0.92 [95% CI, –1.52 to –0.33]; I2 = 74%) without influencing mean arterial pressure (–0.09 [95% CI: –0.40 to 0.22]; I2 = 0%) in patients with HF. Subgroup analysis revealed that the enhanced cardiac function and favorable hemodynamic effects of ketone therapy were also applicable to individuals without HF. Conclusions Ketone therapy may significantly improve cardiac systolic function and hemodynamics in patients with HF and in patients without HF, suggesting it may be a promising treatment for patients with HF and also a beneficial medical strategy for patients without HF or healthy individuals.