Epicardial adipose tissue(EAT)is associated with atrial fibrillation(AF), but the underlying mechanisms remain to be fully elucidated.<Study 1>Left atrial appendage(LAA)samples were obtained from 59 consecutive AF patients during cardiovascular surgery. Histology revealed that the severity of fibrotic remodeling of EAT was associated with left atrial(LA)myocardial fibrosis. Protein concentration analysis demonstrated that the total collagen in the LA myocardium was positively correlated with proinflammatory and profibrotic cytokines/chemokines including interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor, and matrix metalloproteinase-2 and matrix metalloproteinase-9 in EAT. The proinflammatory and profibrotic cytokines/chemokines in EAT and the total collagen in the LA were also positively correlated with angiopoietin-like protein-2(Angptl2)in EAT.<Study 2>We tested the hypothesis that Angptl2 contained in peri-left atrial EAT can induce atrial myocardial fibrosis. Human peri-left atrial EAT and abdominal subcutaneous adipose tissue(SAT)were collected from 9 autopsy cases. EAT- or SAT-conditioned medium was dropped onto the rat left atrial epicardial surface using an organo-culture system. EAT-conditioned medium induced atrial fibrosis in organo-cultured rat atrium with a progressive increase in the number of myofibroblasts. The profibrotic effect of EAT was greater than that of SAT. EAT in patients with AF induced a more significant atrial fibrosis than in those without. Treatment with human recombinant Angptl2 induced fibrosis in organo-cultured rat atrium, which was suppressed by concomitant treatment with Angptl2 antibody. Our results suggested that antagonizing the expression of Angptl2 in EAT could be a useful therapeutic approach to prevent AF.
Atrial antitachycardia pacing(A-ATP)has been reported to reduce atrial tachyarrhythmias(AT/AF)burden. However, little is known about predictive factors of AT/AF burden reduction. The aim of this study was to determine factors of AT/AF burden reduction. Twenty-two patients treated with new-generation A-ATP(Reactive ATP, Medtronic Inc., Minneapolis, MN, USA)were included in this study, and baseline characteristics, intracardiac electrocardiograms(ECGs), and a 12-lead ECGs, Cardiac echography, BNP were obtained. An AT/AF burden reduction of more than 50% was defined as effective. Patients with baseline AT/AF burden of less than 5% were excluded(because it is difficult to determine the effectiveness of treatment)as well as patients with only one episode. The effective group(5 patients)had higher prevalences of longer intracardiac AT/AF average tachycardia cycle length(AvCL)(>300ms)(28.6% vs 5.2%, p<0.05), organized atrial fibrillation(AF)and atrial tachycardia(AT)(71.9% vs 48.5%, p<0.05), and history of catheter ablation(CA)or Maze surgery for AF(80% vs 14%, p<0.02)than those in the ineffective group(7 patients). F wave CL of 12-lead ECGs was significantly larger in the effective group than in the ineffective group(220.5ms vs 141.4ms, p<0.05). A-ATP was effective in longer or organized AF and AT AvCL cases. A history of CA or Maze surgery and long F wave CL in 12-lead ECGs were confirmable predictors of A-ATP efficacy before device implantation.