Therapeutic Translation of Epicardial Adipose Tissue Targeting in Heart Failure With Preserved Ejection Fraction: How Far Are We?

Heart failure with preserved ejection fraction (HFpEF) exhibits an inflammatory-metabolic phenotype in association with multiple factors. Among them, epicardial adipose tissue (EAT), a type of visceral adipose tissue surrounding the heart, has been gaining attention. EAT expansion is associated with the development of HFpEF, the increased risk for heart failure-related mortality in patients with HFpEF, independent of age, body mass index, diabetes, and sex. Thus, reducing EAT expansion has been proposed as a promising therapeutic strategy for treating HFpEF. Although specific treatment for EAT expansion is unavailable, modulating the inflammatory response and systemic energy metabolism are beneficial in improving clinical symptoms or prognosis in patients with HFpEF. To further enhance our capacity in effectively treating HFpEF, this review discusses the knowledge gaps between EAT expansion and the lack of a platform to reduce EAT expansion in HFpEF, including the choices of appropriate animal models, the conceptual mechanisms of glucose and lipid metabolism in EAT expansion toward potential strategies for selective EAT-targeted therapeutic avenues.