The Liraglutide Effects in Atrial Fibrillation (LEAF) Biomarker Study

Background Biomarkers provide prognostic information in atrial fibrillation(AF). Epicardial adipose tissue(EAT) may promote atrial substrate through release of adipokines mediating inflammation and fibrosis. Objectives To evaluate the relationship of left atrial(LA) biomarkers to LAEAT and peripheral biomarkers. Methods Patients with AF with BMI≥27 kg/m2 undergoing catheter ablation were randomized to receive a structured RFM program (n=28) or RFM+liraglutide (n=31) up to 1.8 mg sc daily. Peripheral blood biomarkers were collected at enrollment, prior to ablation, and 12 months post-ablation. During the procedure, LA blood was drawn for biomarker assessment. LAEAT was quantified by CT just prior to ablation. Results Fifteen of 21 markers differed between peripheral and LA samples: CRP, galectin, NT-proANP, troponinT, FFAs, adiponectin, fibrinogen, Activin-A, TGF-ß, MMPs, and TIMPs (p<0.05); many showed strong (r>0.55, p<0.001) correlation (CRP, Galectin, IL-6, Resistin, NT-proANP, NT-proBNP, Adiponectin, Fibrinogen, MMP1), some moderate (r=0.31-0.43) correlation (MCP-1, Troponin T, PAI-1, TIMP1), and some no correlation (TNF-α, FFAs, TGF-β, MMP-2, MMP-8, MMP-9, TIMP-2). Activin-A had a unique bimodal profile. LAEAT volume correlated with MMP-1 (r=0.28, 95%CI 0.00 to 0.52; p=0.049). LAEAT-HU correlated inversely with TIMP-1 (r=−0.37, 95%CI -0.60 to -0.08; p=0.015). Time-dependent changes were observed in NT-proBNP, FFAs, adiponectin, resistin, MMP-2, TIMP-1, and TIMP-2 (p<0.01); there was no treatment effect. Conclusions Differences between pre-ablation peripheral and LA blood biomarkers may reflect changes in EAT and atrial myocardium metabolism and structure, suggesting LA biomarkers may be more relevant to atrial remodeling than peripheral biomarker levels. LA Activin A appears to be a promising biomarker for phenotyping AF.