Epicardial fat remodeling in HFrEF: loss of buffering capacity and lipotoxic risk
M Maczewski, O Luniewska, M M Maczewski, M Nowakowski, L Nogajski, A Sander, K Urbanowicz, B Kutryb-Zajac, P Leszek, L Heather, A PaterekAbstract
Epicardial adipose tissue (EAT) is a metabolically active depot located between the myocardium and pericardium. Under physiological conditions, EAT acts as a local buffer, absorbing excess circulating free fatty acids (FFAs) and protecting the myocardium from lipotoxic stress. In heart failure with reduced ejection fraction (HFrEF), we hypothesize that EAT undergoes inflammatory remodeling that impairs this protective function.
We analyzed EAT volume, density, histology, and radiomic features in HFrEF patients and healthy controls. Although EAT volume did not differ between groups, HFrEF patients showed increased CT density and reduced average adipocyte size in the innermost 2.5 mm layer adjacent to the left ventricle. Radiomic analysis revealed greater tissue heterogeneity in HFrEF, paralleled by a broader adipocyte size distribution- including both numerous small and abnormally large adipocytes-features absent in healthy EAT. These findings suggest a pro-inflammatory shift, with smaller adipocytes potentially reflecting diminished lipid storage capacity.
As previously reported, NEFA levels were elevated in HFrEF, likely due to neurohormonal-driven lipolysis. EAT remodeling may further impair local buffering, increasing myocardial lipotoxic stress.
Myocardial triglyceride (TAG) levels were not significantly increased in HFrEF. Interestingly, patients with denser EAT (≥ –80.5 HU) had lower myocardial TAG concentrations, suggesting that reduced adipocyte storage capacity may increase FFA flux into the myocardium and promote formation of bioactive, potentially toxic lipids.
Our preliminary lipidomic data demonstrate a shift in lipid distribution, with increased accumulation of sphingomyelins and bioactive ceramides in the myocardium, lipid intermediates associated with apoptosis, inflammation, and mitochondrial dysfunction.
These findings demonstrate that impaired EAT buffering may not lead to TAG overload within the myocardium but instead favor accumulation of bioactive, toxic lipids. Ongoing work includes expanded lipidomic profiling and assessment of mitochondrial function. Collectively, our findings suggest that in HFrEF, EAT loses its protective buffering role, contributing to myocardial injury through altered myocardial lipid handling.