Pathophysiological role of epicardial adipose tissue and its phenotypes in patients with diabetes and cardiovascular comorbidities
Authors: Kotha S , Jex N , Chowdhary A , Giannoudi M , Luk C Y , Procter H , Thirunavukarasu S , Cash L , Greenwood J P , Plein S , Kellman P , North N , Levelt E 
Published: November 2023

Abstract

Introduction
Epicardial adipose tissue (EAT) is an active endocrine organ that regulates multiple aspects of cardiac biology including myocardial redox state, intracellular Ca2+ cycling, the electrophysiological and contractile properties of cardiomyocytes, cardiac fibrosis, and coronary atherosclerosis progression.

Purpose
We evaluated associations of CMR-measured EAT area (EATa) with myocardial structure, function and 31P-MRS assessed energetics (phosphocreatine to ATP ratio) in patients with type 2 diabetes (T2D) with and without comorbidities of coronary artery disease (CAD) requiring coronary artery bypass grafting (CABG) and aortic stenosis requiring aortic valve replacement (AVR). We also examined the EAT phenotypes in patients with T2D with and without CAD, CAD patients without T2D and compared them to controls with severe AS without T2D.

Methods
145 participants were recruited including CAD patients undergoing CABG with (30) and without T2D (25); severe AS patients with (20) and without T2D (20) undergoing AVR; T2D patients without cardiovascular disease (30) and healthy controls (20). A month prior to surgery cardiac PCr/ATP; EATa; LV volumes, mass, ejection fraction, mitral inflow E/A ratio, global longitudinal strain (GLS) and myocardial tissue characteristics were assessed. EAT samples were obtained from patients undergoing cardiac surgery for histological assessments.

Results
Participants were matched in age, sex distribution, and body mass index. Across all groups, patients with T2D showed higher EATa compared to those without T2D (138±50 vs 101±51cm2; p&lt;0.0001). EATa was significantly higher in AS patients with T2D versus AS patients without T2D, while there was no significant difference in EATa between the CAD patients with and without T2D. Among the structural parameters, there were significant correlations between the EATa and myocardial pre-contrast T1 (p=0.02; r=0.20). Among the functional parameters there were inverse correlations of EATa with mitral inflow E/A (r=-0.34, p=0.002) and with GLS (r=-0.23, p=0.009). Among the metabolic biomarkers, there were no correlations between the EATa and PCr/ATP ratio. Histologically, compared to the control group of AS patients without T2D, patients with CAD with and without T2D showed larger adipocyte size and higher tissue fibrosis. There were no significant differences in EAT phenotype in adipocyte size, tissue fibrosis or inflammation between CAD patients with and without T2D.

Conclusions
This comprehensive EAT phenotyping study combined invasive and non-invasive methodologies and showed similar magnitudes of changes in EATa, adipocyte size and EAT fibrosis in CAD patients with and without T2D. While we have detected significant relationship of the EATa with the myocardial fibrosis, diastolic function and GLS, there were no correlations of myocardial PCr/ATP with the EATa suggesting other key mechanisms involved in the energetic deficit in patients with T2D.