Abstract 13179: Distinct Biomarker Profiles for Pediatric and Adult Dilated Cardiomyopathy

Abstract

Introduction: Pediatric and adult dilated cardiomyopathy (DCM) represent distinct entities with divergent gene expression, histopathology, and response to medical therapies. Prognostically important serum biomarkers identified in adults have failed to provide similar diagnostic and prognostic information for children with DCM. We hypothesized that pediatric and adult DCM populations display different biomarker profiles. Methods: Pediatric control (≤18y), pediatric DCM, and adult DCM plasma samples were analyzed using the SOMAscan biomarker platform to simultaneously measure over 1300 known protein analytes. Pediatric control and DCM subjects were age- and gender-matched. Most samples were obtained within 2 years of diagnosis. Biomarkers were compared between groups with p-value <0.05 (false discovery rate) and fold change (ratio of means) >2 considered significant. Principal component analysis was used to visualize differences in proteomic data. Results: The study included 39 pediatric control (mean age 3y, IQR 1-14), 39 pediatric DCM (median age 2.7y, IQR 1-13), and 40 adult DCM (median age 53y, IQR 46-63) subjects. Twenty plasma peptides were upregulated in pediatric DCM compared to controls. Plasma renin and 6-phosphogluconate dehydrogenase represented potential pediatric-specific biomarkers. Pediatric DCM subjects clustered into 4 distinct subgroups with unique biomarker profiles and distinguishing clinical characteristics suggesting the pediatric DCM phenotype may represent a heterogeneous group of diseases. Conclusions: This feasibility study provides important evidence that distinct biomarker profiles are present in pediatric and adult DCM patients. These findings provide preliminary data to inform the design of larger prospective studies to validate pediatric DCM specific biomarkers and investigate their prognostic value.