Clinical Electrophysiology -> Atrial Fibrillation & Atrial Flutter: -> Physiology D-PO01 - Featured Poster Session (ID 11) Poster

D-PO01-020 - Structural Remodeling Precedes The First Onset Of Atrial Fibrillation (ID 883)

Abstract

Background: Several well studied pathophysiological processes have been associated with the prevalence of atrial fibrillation (AF). However, empirical data on the biological processes (BP) that are active in human atrial myocardium before the first onset of AF are lacking.
Objective: To determine the over-represented BPs that are active in the atrial myocardium preceding the first onset of AF.
Methods: We selected patients without a history of AF who participated in the PREDICT AF trial (NCT03130985). In this trial, 150 patients underwent CABG/valvular surgery with left atrial appendage (LAA) removal. Patients were followed after 1, 6, 12 and 24 months with Holter and ECGs. The primary endpoint was any atrial tachyarrhythmia on ECG or continuous monitoring >30s after the first 30 days. For the current study we performed whole transcriptome sequencing in 22 LAAs of PREDICT AF patients. We then determined the active BP in patients who develop new-onset AF by gene set enrichment analysis (GSEA).
Results: 7 out of 22 patients developed an atrial tachyarrhythmia >30 days after surgery. Two of these developed both postoperative AF and new-onset AF <40 days. Excluding these 2 patients we found 995 differentially expressed genes (non-adjusted p<0.05). GSEA revealed 116 upregulated BP (FDR-adjusted p<0.1), primarily related to extracellular matrix (ECM) remodeling such as BMP signaling, ECM proteoglycans and Collagens (figure).
Conclusion: Significant ECM remodeling occurs within the atrium before the first onset of AF and is composed of a composite of signaling pathways, synthesis of various ECM proteins and ECM receptor signaling. Early detection of these changes may help to prevent future AF.
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