Longitudinal Plasma Proteome Changes Before and After Catheter Ablation in Atrial Fibrillation

Abstract Background Proteins in human plasma serve as critical markers for predicting disease risk and guiding therapeutic development. Current prediction models for atrial fibrillation (AF) largely rely on electronic health records; however, the plasma proteome of patients with AF reflects key biological processes, including inflammation, that are not captured by clinical variables alone. Circulating inflammatory mediators contribute to electrical and structural remodelling in the atria, thereby sustaining the AF phenotype. Identification of plasma proteins associated with AF may therefore improve understanding of the inflammatory and other biological processes underlying AF pathophysiology. Objective In this study, we profiled the plasma proteome of patients with paroxysmal AF (pxAF), persistent AF (persAF), and non-AF controls using Olink assay technology. Methods Plasma samples from 30 individuals were analysed with the Olink Reveal panel. Differential expression analysis of normalised protein expression (NPX) values was performed between groups, with differentially expressed proteins (DEPs) defined by P < 0.05. Results We identified 87 DEPs in pxAF and 107 DEPs in persAF compared with controls. From these, we shortlisted 11 candidate proteins that were upregulated in persAF at baseline and showed reduced expression 12 months after catheter ablation. This subset of proteins is implicated in the regulation of inflammation (CCL23, CXCL10, IL33), metabolism (ALDH3A1, NDUFS6), cell-matrix adhesion (AFAP1L1, LGALS7, SPOCK1), and physiological signalling (NOS1, PROK1, PTH). Conclusion Collectively, these plasma proteins highlight systemic molecular mechanisms contributing to AF pathogenesis and represent potential AF-specific biomarkers warranting further investigation in larger clinical cohorts and mechanistic studies.