The epicardial adipose tissue volume is in patients with type 2 diabetes mellitus associated with a lowered myocardial perfusion reserve

Abstract Introduction The epicardial adipose tissue (EAT) has unobstructed vascular connection to the myocardium and has a secretome very different from that of other fat depots. The EAT fat pad and its paracrine and vasocrine secretion of pro-inflammatory and profibrotic cytokines is suggested to contribute to heart failure with preserved ejection fraction (HFpEF) pathogenesis albeit via unknown mechanisms. Animal studies and magnetic resonance imaging studies in patients with type 2 diabetes mellitus (T2DM) have documented that important myocardial changes linking diabetic cardiomyopathy to systolic and diastolic dysfunction are myocardial microvascular dysfunction and myocardial fibrosis. Purpose To investigate whether a high volume of EAT is associated with impaired myocardial perfusion reserve (MPR) or disperse fibrosis in patients with T2DM. Methods 198 patients with T2DM but without ischemic heart disease were identified from a cross-sectional cardiovascular magnetic resonance imaging cohort study. 25 healthy controls were included for characterization of baseline characteristics. With gadolinium for contrast, MPR was determined by perfusion sequences and disperse fibrosis was determined from the myocardial extracellular volume (ECV). Volumes of EAT and pericardial adipose tissue (PAT) were determined from cine images. Results The T2DM patients (69% male) had a median age 59 IQR [50, 67] yrs, BMI 30.7 IQR [27.8, 33.7] kg/m2, and EAT of 17.3 IQR [14.2, 22.4] cm2. All patients had normal left ventricle ejection fraction. Compared to the healthy controls, patients with T2DM had higher BMI, abdominal circumference, ECV, EAT, and PAT volumes, and lower MPR (all p<0.001). In univariable regression analysis, EAT and PAT were both associated with higher BMI, abdominal circumference, and age (all p<0.02). In multivariable regression analysis, however, with adjustments for age, sex, BMI, and T2DM-duration, only EAT and MPR were significantly associated (P<0.01), whereas EAT and ECV were not. The PAT volume was not associated with MPR nor ECV. High-sensitive CRP was associated with the EAT volume (p<0.001), but hs-CRP was not associated with MPR or ECV. Conclusion An increased epicardial adipose tissue volume is in patients with T2DM associated with myocardial microvascular dysfunction. Irrespective of a generally heightened inflammatory level, the mechanism by which EAT contribute to development of HFpEF is therefore possibly via an EAT-induced impairment of the myocardial perfusion reserve. Randomized studies targeting a decreased epicardial adipose tissue volume are needed to demonstrate if this will improve myocardial microvascular dysfunction and hence limit development of HFpEF in patients with T2DM.Univariable analysis of EAT and ECVUnivariable analysis of EAT and MPR