Epicardial fat and atrial fibrillation: The role of profibrinogenic mediators

Abstract

Background. Epicardial adipose tissue (EAT) has certain paracrine functions, which could be associated with proinflammatory and fibrotic changes in myocardium even in patients without structural heart disease but with atrial fibrillation (AF). Purpose: to evaluate interrelationship between clinical data, parameters of tissue Doppler imaging (TDI), EAT thickness estimated by magnetic resonance imaging (MRI), and biochemical markers of fibrosis and inflammation in patients with nonvalvular AF without concomitant ischemic heart disease (IHD). Materials and Methods. We included in this study 39 AF patients without valvular pathology or IHD with normal or moderately increased left atrial (LA) dimension (mean age 50.8±13.9 years, 49 % men). The following groups were distinguished for analysis: with idiopathic AF (iAFgroup, n=21); with AF and arterial hypertension (AF+AH group, n=18); with normal (<4.5cm) (n=29), and with slightly enlarged (=4.5cm) LA dimensions (n=10). Besides standard ECG and echocardiography (ECHO), all patients underwent TDI and cardiac MRI with late gadolinium enhancement (LGE). Periventricular EAT thickness and LA fibrosis were calculated by MRI. Examination also included measurement of levels of matrix metalloproteinases (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), transforming growth factor ß1 (TGF-ß1), and soluble intercellular adhesion molecule (sICAM). Results. Most close correlations were found between EAT thickness and levels of the following biomarkers were found to closest: MMP-9 (t=0.65; Tcr=0, 16), TIMP-1 (t=0, 71; Tcr=0, 18) in iAF group; and TGF-ß1 (t=0.22; Tcr=0.19) in the whole group. The LA fibrosis (%) was associated with TIMP-1 with strongest correlation in iAF group (t=0.72; Tcr 0.21). Myocardial mass was significantly associated with TGF-ß1 in the group with LA<4.5cm (t=0.92, Tcr 0.14), and with LA=4.5cm (t=0.81, Tcr 0.24). E/e' by TDI correlated with levels of MMP-9 and TIMP-1 (t=0.65, Tcr=0.16, and t=0.56, Tcr=0.21, respectively), and with TGF-ß1 being closest in the group with LA <4.5 cm (t=0, 57; Tcr 0, 14). Among clinical factors body mass was slightly associated with EAT (t=0.33, Tcr=0.26). Conclusion. The EAT and LA fibrosis by LGE MRI is significantly associated with markers of fibrosis (MMP-9, TIMP-1, TGF-ß1) in patients with AF without structural heart disease. Elevation of MMP-9 and TIMP-1 levels are associated with LV diastolic dysfunction in these patients, what can reflect initial signs of atrial cardiomyopathy even in patients with nonvalvular "nonischemic" AF with normal or slightly enlarged LA.