Abstract 12698: Myocardial Infiltration of the Epicardial Adipose Tissue in Human Heart Failure

Abstract

Introduction: The epicardial adipose tissue (EAT) is adipose tissue that is contiguous with the myocardium without barrier. However, there is a fundamental gap in knowledge for the EAT’s role in health and disease. Methods: We employed single-nucleus RNA sequencing (snRNAseq) and molecular techniques to phenotype human EAT procured from patients with heart failure (HF) secondary to dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). EAT was harvested from the right and left ventricles (RV and LV) of 10 healthy control (CTRL) donors ((median age: 54.0 (interquartile range [IQR]: 49.0-57.9) years; 5 [50.0%] males; median BMI: 25.0 ([IQR]: 24.5-28.2) kg/m 2 ), 32 DCM patients ((median age: 55.0 (interquartile range [IQR]: 48.0-60.7) years; 16 [50.0%] males; median BMI: 26.1 ([IQR]: 23.0-30.3) kg/m 2 ) and 22 IHD patients ((median age: 57.5 (interquartile range [IQR]: 52.5-64.5) years; 13 [59.1%] males; median BMI: 27.2 ([IQR]: 25.1-30.7) kg/m 2 ). HF patients were age (p=0.668 (DCM); p=0.172 (IHD)), sex (p>0.999 (DCM); p=0.712 (IHD)), and BMI (p=0.711 (DCM); p=0.515 (IHD)) matched to CTRL. Results: There was a significant expansion of EAT over the LV (mean EAT thickness in CTRL: 1.11mm, DCM: 2.75mm (p=0.002) and IHD: 3.31mm (p<0.001)) and the RV (mean EAT thickness in CTRL: 2.24mm, DCM: 5.57mm (p=0.029) and IHD: 5.11mm (p=0.065)) in HF. There was only a regional expansion of EAT over the LV of IHD patients. Data were analyzed using one-way ANOVA with Tukey’s post hoc test. Histological staining revealed myocardial EAT infiltration in HF, which was absent in CTRL. Nuclei isolated from EAT and adjacent myocardium were then subjected to snRNAseq. The transcriptional signature of HF intramyocardial adipocytes closely resembled unique cell states and gene expression identified in the EAT, suggesting infiltration by the EAT. By contrast, myocardial adipocytes in CTRL tissue were distinct from the EAT. The adipocytes in the interventricular septum, which lacks contiguous EAT, were similar in HF and CTRL. Conclusion: The proximity of the EAT confers a unique position to directly modulate the myocardium. As such, targeting pathogenic EAT expansion and infiltration may be critical to the development of novel therapeutic strategies in HF patients.