Uncovering the Role of Epicardial Adipose Tissue in Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure. Obesity is a modifiable risk factor of HFpEF; however, body mass index provides limited information on visceral adiposity and patients with similar anthropometrics can present variable cardiovascular risk. Epicardial adipose tissue (EAT) is the closest fat deposit to the heart and has been proposed as a biomarker of visceral adiposity. EAT may be particularly important for cardiac function, because of its location (under the pericardium) and because it acts as a metabolically active endocrine organ (which can produce both beneficial and detrimental cytokines). In this paper, the authors review the role of EAT in normal and pathologic conditions and discuss the noninvasive imaging modalities that allow its identification. This review highlights EAT implications in HFpEF and discuss new therapies that act on EAT and might also exert beneficial effects on the cardiovascular system. • HFpEF is associated with a broad range of metabolic comorbidities, epicardial and intramyocardial fat expansion, and imbalances in adipocyte-associated pro-inflammatory cytokines. • EAT can produce both beneficial and detrimental cytokines, which are easily transmitted to the myocardium via the vasa vasorum, paracrine function, and extracellular vesicles. Under certain stimuli, expanded and dysfunctional EAT shifts its biology and releases pro-inflammatory and fibrotic cytokines, thus fostering (and precipitating) HFpEF. • SGLT2i reduce EAT volume, mute its pro-inflammatory characteristics, and reduce outcomes in large-scale definitively powered trials in HFpEF.