Abstract Body: Ventricular pacing-induced heart failure in canines is a well-established large animal model that closely recapitulates the structural, functional, and molecular characteristics of human dilated cardiomyopathy (DCM). Despite significant advances in understanding the pathological remodeling associated with DCM, the molecular mechanisms particularly the role of non-coding RNAs remain undefined. Circular RNAs (circRNAs), a unique class of non-coding RNAs characterized by their covalently closed loop structures, have recently emerged as critical regulators of gene expression, influencing various cellular processes such as transcription, splicing, and translation. However, their contribution to the pathogenesis of DCM is still largely unexplored. In this study, we conducted high-throughput RNA sequencing analysis on ventricular tissues obtained from four control and four ventricular-paced canine hearts to investigate the differential expression in circRNAs associated with pacing-induced heart failure. Our comprehensive analysis identified several circRNAs that were significantly dysregulated between the control and heart failure groups. Among them, key circRNAs exhibiting the most notable changes were prioritized for further validation and functional characterization. This study provides novel insights into the dynamic regulation of circRNAs during the progression of DCM. The identified circRNAs could potentially serve as biomarkers for disease diagnosis or prognosis and might represent promising therapeutic targets for mitigating adverse cardiac remodeling. Overall, our findings lay an important foundation for future mechanistic studies aimed at unraveling the functional roles of circRNAs in heart failure and advancing RNA-based therapeutic strategies for human DCM.