The Application of Epicardium in Heart Failure Treatment: Opportunities and Challenges.

Heart failure remains one of the leading causes of morbidity and mortality worldwide. Conventional treatment strategies, while beneficial, face numerous limitations. Drug therapies may lead to resistance, while device-based treatments such as LVAD and ICD carry risks of infection, bleeding, device failure, and high costs. For end-stage heart failure, heart transplantation is further constrained by donor shortages and immune rejection. In contrast, cell-based therapies have emerged as a promising alternative. Recent studies have highlighted the critical role of the epicardium and epicardium-derived cells (EPDCs) in cardiac regeneration. These cells contribute to heart repair through multiple mechanisms, including direct cell therapy, the development of epicardium-based biomaterials, and integration with gene therapy approaches. This review outlines the anatomical structure and biological functions of the epicardium, explores the regenerative potential of the epicardium and EPDCs, and evaluates their application in heart failure treatment. Furthermore, it discusses the translational potential and current challenges associated with epicardial-based therapies, offering novel insights and strategies for heart failure management.