Pharmacologic and Lifestyle Interventions to Modulate the Epigenome in Heart Failure

Heart failure (HF) remains a major global health concern with high morbidity and mortality, particularly in cases with preserved ejection fraction, where treatment options are limited. Epigenetic mechanisms, including DNA methylation, histone modification, and noncoding RNAs, are increasingly recognized for their role in HF development and progression. These processes integrate genetic and environmental signals, offering novel targets for therapy. Emerging pharmacologic agents, alongside repurposed drugs with epigenetic effects, show promising results. Additionally, lifestyle factors such as diet and exercise influence the epigenome, opening new avenues for personalized, nonpharmacological interventions aimed at modifying disease trajectory and improving clinical outcomes.