Epicardial adipose tissue: a potential biomarker and therapeutic target in patients with paradoxical low-gradient aortic stenosis and preserved ejection fraction.

Paradoxical low-flow, low-gradient (LFLG) aortic stenosis (AS) with preserved ejection fraction (ASpEF) is a severe AS subtype associated with worse prognosis and increased mortality compared with high-gradient AS. Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the myocardium, has emerged as a potential biomarker and therapeutic target in this population. EAT influences myocardial and valvular pathology through mechanical compression, metabolic alterations, and secretion of inflammatory mediators such as IL-6, MCP-1, and TNF-α, contributing to left ventricular remodeling and aortic valve degeneration. Recent metabolomic studies demonstrate significant associations between EAT thickness and both positively and negatively correlated metabolites, underscoring its complex role in disease progression. Despite its promise, challenges remain due to limited understanding of EAT-myocardium interactions, variable patient presentation, and confounding factors such as insulin resistance and obesity. Further research is warranted to clarify EAT's pathophysiological role, prognostic value, and therapeutic potential in managing paradoxical LFLG ASpEF.