Serum Lipopolysaccharide Is Associated with the Recurrence of Atrial Fibrillation after Radiofrequency Ablation by Increasing Systemic Inflammation and Atrial Fibrosis

Abstract

Objectives. The gut microbiota and its metabolites are linked to inflammation and contribute to the progression of atrial fibrillation (AF), but the predictive value of the gut microbiota-derived metabolite lipopolysaccharide (LPS) for AF recurrence (RAF) is unknown. This study is aimed at investigating (1) the correlation between LPS and RAF and (2) its relationship with inflammation and atrial fibrosis. Method. We performed a single-centre retrospective analysis in 159 AF patients. Fasting plasma samples were collected, and an enzyme-linked immunosorbent assay was used to determine the levels of serum LPS, interleukin-6 (IL-6), collagen type-1 C-terminal telopeptide (CITP), and transforming growth factor-β1 (TGFβ1). The cumulative risk for RAF was evaluated with Kaplan–Meier analysis. Cox proportional hazard analysis was carried out to predict the hazard of RAF. The correlations among LPS and IL-6, CITP, TGFβ1, and left atrial diameter (LAD) were analysed by Pearson’s correlation coefficient. Subsequent univariate and multivariable linear regression analyses were carried out to evaluate the connection between clinical variables and Log-LPS. Results. All 159 AF patients were included in this study. The proportion of persistent atrial fibrillation was 40.3%, the mean age was $61.9\pm 10.1$ years, the proportion of males was 61.6%, and the mean LPS was $56.5\pm 29.5$  pg/mL. After all patients were divided into tertiles according to the circulating LPS level, a total of 44 RAF occurred: 10 in the first tertile, 15 in the second tertile, and 19 in the third tertile (log-rank test $P=0.037$ ). Heart failure (hazard ratio 2.029, $P=0.041$ ), LAD (hazard ratio 1.064, $P=0.022$ ), Log-LPS (hazard ratio 5.686, $P=0.043$ ), and CITP (hazard ratio 6.841, $P=0.033$ ) independently predicted the risk of RAF. In all patients, univariate analysis showed that heart failure, LAD, hs-CRP, IL-6, CITP, and TGF-β1 were connected with Log-LPS. Multivariate linear regression analysis indicated that IL-6 and hs-CRP were independently and positively connected with Log-LPS. Conclusions. Our results indicated that circulating LPS was a predictor of RAF and may contribute to RAF incidence after ablation by increasing systemic inflammation and atrial fibrosis.