Abstract 12866: Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome

Introduction: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. Objectives: This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes. Methods: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against those 429 donors from the GTEx project without cardiac background. Results: The IHD transcriptome was characterized using repressed RNA expressions in pathways for cell-cell contacts and mitochondrial dysfunction. Specifically, we identified the increased expressions of the CSRNP3 , FUT10 , SHD , NAV2-AS4 , and hsa-mir-181 genes to correlate with the complexity of coronary artery obstructions or with a functional cardiac benefit from bypass surgery. Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes we characterized here pave the way for disease mechanism-based identification of biomarkers allowing for the early detection and treatment of IHD.