Circulating Metabolomic Profile and its Association with Atrial Fibrillation and Systemic Inflammation.

Background: Atrial fibrillation (AF) is a prevalent arrhythmia associated with chronic inflammation and metabolic dysregulation.Metabolic and inflammatory pathways may influence atrial electrophysiology and structural remodeling, contributing to AF onset and persistence, yet key circulating signatures remain poorly defined.Objective: To characterize systemic inflammatory markers and circulating metabolomic profiles in patients with paroxysmal and persistent AF compared to non-AF controls. Methods:In this prospective study, 101 patients were enrolled (mean age 59.9 14.7 years; 72% males) including 41 with paroxysmal AF, 30 with persistent AF, and 30 controls.Fasting plasma samples were analysed using targeted gas chromatography-mass spectrometry to quantify 156 metabolites and multiplex flow cytometry to profile 13 inflammatory cytokines.Results: IL-18 concentrations were significantly elevated in AF patients compared to controls (p = 0.009), with highest levels observed in those with persistent AF.No significant differences were observed in IL-6 or hsCRP.Nine metabolites showed significant differential abundance between AF and controls.Metabolites including Pyridoxine, N-Acetylglutamine, 3-Dehydroquinate, D-Glucose, Glucosamine, Ascorbic acid, and Galacturonic acid were reduced in AF, while capric and caprylic acid were elevated.Beta-alanine was the only metabolite increased in persistent AF relative to both paroxysmal AF and controls.TMAO concentrations did not differ significantly between groups.