Abstract 18860: Molecular Pathways Altered in Pediatric Dilated Cardiomyopathy Hearts Are Dependent on Disease Etiology

Abstract

Introduction: Dilated cardiomyopathy presents a significant clinical burden in pediatric patients due to limited effective treatment options. This study hypothesizes molecular alterations in the heart of pediatric dilated cardiomyopathy (DCM) patients are dependent on specific etiologies. By understanding the molecular mechanisms underlying different etiologies, we aim to enhance diagnostics and guide future targeted therapies. An advanced understanding of the molecular mechanisms of DCM holds potential to transform pediatric cardiovascular care. Methods: RNA was extracted from the IRB approved University of Colorado's pediatric cardiac tissue bank. Samples included non-failing (NF), idiopathic dilated cardiomyopathy (IDCM), myocarditis, and left-ventricle non-compaction (LVNC) hearts. RNA-seq was performed using the Illumina HiSeq 4000 platform, and aligned using the TOPmed RNA-seq pipeline. Statistical analysis between NF and each etiology was performed to identify fold changes and q-values. Gene expression analysis was further examined using Ingenuity Pathway Analysis (Qiagen). Results: Demographics of patient samples were as follows: NF (N=23, % male=61%, Median age=13.65 years, Interquartile range (IQR)=8.6), IDCM (N=20, % male=55%, Median age=9.83 years, IQR=8.98), myocarditis (N=4, % male=75%, Median age=0.35 years, IQR=0.1), LVNC (N=3, % male=33.3%, Median age=0.27 years, IQR= Undetermined). Comparisons between NF versus IDCM, NF versus myocarditis, and NF versus LVNC hearts revealed noteworthy differences in gene expression patterns. Pathways associated with IDCM related to inflammation and immune response trends, whereas DNA repair and cellular damage were strongly associated with myocarditis. Lastly, analysis of LVNC hearts suggest pathways associated with ischemic remodeling. Conclusions: In conclusion, our study provides insights into gene expression patterns associated with different etiologies of DCM in pediatric patients. Distinct patterns were observed between non-failing and IDCM, myocarditis, or LVNC hearts. These findings have implications for improving diagnostics and guiding targeted therapies in pediatric DCM management.