Abstract 4144103: Circulating miRNAs are Differentially Expressed in Pediatric Dilated Cardiomyopathy Patients with Favorable vs. Poor Outcomes

Introduction: microRNAs (miRs) are small single stranded RNAs capable of targeting expression of several genes. Circulating miRs can be important biomarkers of disease progression. Children with dilated cardiomyopathy (DCM) experience multiple outcomes including recovered-normalization, stable disease, and progression to death/ need for transplant. We hypothesized that circulating miRs are differentially expressed among these cohorts and may serve as useful prognostic biomarkers in pediatric DCM patients. Methods: RNA-sequencing was used to detect and quantify circulating miRs. Samples were collected within 3 months of a new diagnosis of DCM. Inclusion criteria included <18 years of age at diagnosis of idiopathic or familial DCM (LVEF<50% or left ventricular end-diastolic dimension [LVEDd] z-score ≥+2). Primary outcomes within 1 year of enrollment were defined as: [1] Death, cardiac transplant, or initiation of mechanical circulatory support; [2] Recovered-normalization of LVsize and function (LVEF≥50% and LVEDd z-score <+2) or [3] Stable-persistent DCM with LVEF<50% or LVEDd z-score ≥+2. Statistical analysis included random forest and hierarchical clustering (HC). Results: Sequencing was performed on 76 patients: death/transplant (n=35), recovered (n=20), or stable DCM (n=21). The top three differentially expressed miRs between the death/transplant and recovery group were miR-424-5p, miR-335-5p, and miR-503-5p (Figure A). HC based on expression of these 3 miRs identified an expression pattern associated with death/transplant outcome (Figure B). miR-503-5p was also among the top 3 miRs most differentially expressed between the stable and the recovery group. Conclusions: These results indicate circulating miRs can predict recovery in the pediatric DCM population. Importantly, miR-503-5p was more highly expressed in the recovery group when compared to both the stable and transplant groups, suggesting expression of this miR may be associated with favorable outcomes. A unique biomarker signature of miRs specific to children with DCM who have the potential to recover would improve risk stratification of this population.