Abstract 4368849: Comparative Transcriptomic Analysis of Atrial Chambers in Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with progressive atrial remodeling. Although clinical interventions often target the left atrium, molecular differences between atrial chambers may influence AF persistence and therapeutic response. Hypothesis: We hypothesized that transcriptomic signatures consistently differentiate the left atrial appendage (LAA) from the right atrial appendage (RAA) in patients with AF and that conserved biomarkers can be identified across independent datasets. Goals: To identify robust, cross-dataset gene expression markers distinguishing LAA from RAA, with potential implications for chamber-specific therapeutic targeting in AF. Methods: Gene expression profiles were obtained from three publicly available microarray datasets (GSE41177, GSE115574, and GSE79768), comprising 85 atrial tissue samples. Differentially expressed genes (DEGs) between LAA and RAA were identified using the limma package. Functional enrichment analysis was conducted using Gene Ontology and KEGG databases. Protein–protein interaction (PPI) networks were constructed using STRING to identify hub genes. Expression validation was visualized through boxplots. Results: We identified 140 unique DEGs, with 32 genes overlapping in two or more datasets. Enrichment analysis revealed significant involvement in atrial morphogenesis, cardiac chamber specification, and bone morphogenetic protein (BMP) signaling. PPI network analysis highlighted BMP10 and PITX2 as central hub genes, each exhibiting consistently enriched expression in LAA across datasets. These patterns were confirmed through cross-dataset boxplot visualization. Conclusion: BMP10 and PITX2 represent conserved transcriptomic markers differentiating LAA from RAA in patients with AF. These genes may serve as biomarkers of chamber-specific remodeling and inform personalized AF management strategies, including targeted ablation or atrial-selective drug development.