Abstract 4371113: Differential Gene Expression Signatures Underlying Postoperative Atrial Fibrillation

Abstract

Introduction: Postoperative atrial fibrillation (poAF) is a serious complication following cardiac surgery, contributing to increased ICU and hospital length of stay, heightened stroke risk, and increased morbidity and mortality. While clinical risk factors such as obesity, hypertension, and a history of atrial fibrillation are known contributors, the genetic mechanisms driving poAF in cardiac surgery patients are not well understood. Thus, understanding the specific gene expression changes in atrial tissues associated with poAF may provide insights into pathophysiology and highlight novel therapeutic targets. Hypothesis: This study aims to compare left atrial transcriptome profile in patients with poAF to those without to identify the genes that are differentially expressed. Methods/Approach: We performed bulk-RNA sequencing on left atrial tissue collected from 86 patients undergoing mitral valve surgery. Differential gene expression (DGE) analysis was then performed to determine genes significantly associated with poAF status using DESeq2, accounting for key covariates including patient age, sex, sequencing batch year, left atrial size, left ventricular ejection fraction, and prior history of atrial fibrillation. P-values following DGE were then adjusted using Benjamini-Hochberg correction to minimize False Discovery Rate. Results: We identified 35 genes demonstrating statistically significant expression (adjusted p-value < 0.05, absolute log2 fold change > 1) between patients who developed poAF and those who did not. Among the identified differential expressed genes, immune-related genes such as JCHAIN were upregulated and regulatory non-coding RNAs including ARHGAP26-AS1 and LIN28AP2 were highly downregulated. Notably, RPL21P70, a pseudogene of the RPL21 gene expressed in heart muscle, was heavily downregulated. These genes may contribute to atrial remodeling and inflammatory processes involved in atrial fibrillation. Conclusion: Our study revealed a set of differentially expressed genes associated with the development of post-operative atrial fibrillation in cardiac surgery patients. While several of these genes play roles in immune signaling and RNA regulation, a notable portion consisted of pseudogenes, whose biological function remains poorly understood. Future exploration into upregulation and downregulation of identified genes provide a basis for further study and highlight potential targets for therapeutic intervention.