Evaluating the Utility of a New Pathogenicity Predictor for Pediatric Cardiomyopathy

Abstract

Pediatric cardiomyopathy (CM) has significant childhood morbidity and mortality which is caused by both genetic and environmental factors. Previous research has focused on identifying genetic variants in pediatric CM for diagnostic purposes, but not for risk stratification. The current study was modeled after previous work which showed an association between CardioBoost-classified disease-causing variants and an increased risk for severe clinical outcomes in adults with CM to assess if the same association is true in pediatric CM. This was a retrospective, single-center cohort study that evaluated outcomes in pediatric CM patients who were evaluated by the Children’s Hospital of Philadelphia (CHOP). CardioBoost (CB) scores were generated for these patients, and scores were categorized as ≤0.1, 0.1-0.9, and ≥0.9. Composite endpoint was freedom from a major adverse cardiac event (MACE). 104 patients were included in the final analysis. 32 (31%) had DCM, 45 (43%) had HCM, and 27 (26%) had other CM. There was no significant association between CB score and clinical outcome in pediatric CM patients. Overall, this study highlights the continued deficits in variant interpretation for pediatric CM. We recommend using caution when applying this tool to stratify clinical outcomes in the pediatric population.