Unraveling the Complex Pathophysiology of Heart Failure with Preserved Ejection Fraction: Mechanistic Insights and Therapeutic Frontiers

Heart failure with preserved ejection fraction (HFpEF) represents a significant and growing subset of heart failure cases, characterized by clinical signs and symptoms of heart failure despite a normal or near-normal left ventricular ejection fraction (LVEF). Unlike heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying HFpEF are multifactorial and complex, involving intricate interactions between comorbidities, myocardial structural and functional abnormalities, and systemic inflammatory responses. This review delves into the intricate pathophysiology of HFpEF, exploring the roles of myocardial fibrosis, ventricular-arterial coupling, endothelial dysfunction, and extracardiac factors such as obesity, diabetes, and hypertension. Understanding these mechanisms is crucial for the development of targeted therapeutic strategies aimed at improving patient outcomes in HFpEF.