Evaluating the Utility of a New Pathogenicity Predictor for Pediatric Cardiomyopathy

Area of Science:

• Cardiology
• Genetics
• Pediatrics

Background:

• Pediatric cardiomyopathy (CM) contributes to significant childhood morbidity and mortality.
• Genetic factors are key contributors to pediatric CM, but variant interpretation for risk stratification remains challenging.
• Previous studies linked CardioBoost (CB) scores to severe outcomes in adult CM, prompting investigation in pediatric populations.

Purpose of the Study:

• To evaluate the association between CardioBoost (CB) scores and clinical outcomes in pediatric cardiomyopathy patients.
• To determine if CB-classified disease-causing variants can stratify risk for severe clinical outcomes in children with CM.
• To assess the utility of the CardioBoost tool in the pediatric CM population.

Main Methods:

• Retrospective, single-center cohort study of 104 pediatric CM patients evaluated at Children's Hospital of Philadelphia.
• CardioBoost (CB) scores were calculated and categorized (≤0.1, 0.1-0.9, ≥0.9).
• Major adverse cardiac event (MACE) served as the composite endpoint to assess clinical outcomes.

Main Results:

• No significant association was found between CB score categories and the risk of MACE in pediatric CM patients.
• The study included diverse pediatric CM types: 31% dilated CM (DCM), 43% hypertrophic CM (HCM), and 26% other CM.
• The findings indicate limitations in applying adult-derived variant interpretation tools to pediatric populations.

Conclusions:

• The CardioBoost scoring system did not demonstrate significant predictive value for clinical outcomes in pediatric cardiomyopathy.
• This study underscores the ongoing challenges and deficits in interpreting genetic variants for risk stratification in pediatric CM.
• Caution is advised when utilizing the CardioBoost tool for clinical outcome stratification in pediatric CM patients.