Enhanced neutrophil extracellular traps formation in AF patients with dilated left atrium.

Abstract

Atrial fibrillation (AF) is associated with cardiac remodelling and prothrombotic state. Enhanced neutrophil extracellular traps (NETs) formation has been reported in AF, contributing to thromboembolism. We investigated whether increased left atrium (LA) diameter and reduced left ventricular ejection fraction (LVEF) affect NETs formation and prothrombotic state in AF patients. In 243 AF patients (median CHA2 DS2 -VASc=4) we measured LA diameter and LVEF, 123 of them with LVEF<50%. Moreover, we determined 3 markers of NETosis: circulating citrullinated histone H3 (H3cit), myeloperoxidase (MPO) and peptidylarginine deiminase 4 (PAD4), along with prothrombotic markers, including endogenous thrombin potential, plasma fibrin clot permeability (Ks ) and clot lysis time (CLT). Ischaemic cerebrovascular events, major bleeding and death were recorded during a median follow-up of 53 months, on anticoagulation. LA diameter correlated positively with H3cit, MPO and PAD4, while LVEF was inversely associated with the same NETosis markers. After adjustment for age and body mass index, concentrations of MPO (per 10units; β=-1.9, 95%CI -3.40;-0.42) and H3cit (per 10units; β=2.02, 95%CI 0.61-3.42) were independently associated with LVEF and LA diameter. LA diameter, but not LVEF, correlated inversely with Ks and positively with CLT. The Cox regression analysis revealed that H3cit >6.16 ng/mL (HR=21.76, 95%CI 2.85-166.28, p=.003) and LA diameter > 46 mm (HR=2.89, 95%CI 1.04-8.03, p=.043) independently predicted cerebrovascular ischaemic events (1.9%/year). This hypothesis-generating study suggests that in AF enlarged LA diameter and reduced LVEF are associated with enhanced NETs formation, which might have clinical importance and contribute to thromboembolic events despite anticoagulation.