Key result
Sarcomere gene variants linked to ~10-fold higher sudden cardiac arrest risk in pediatric HCM.
Why the study?
Sudden cardiac arrest is a leading cause of death in pediatric hypertrophic cardiomyopathy, but clinical and genetic characteristics and the applicability of current risk prediction models needed assessment.
Do the HCM Risk-Kids and PRIMaCY genetic scoring systems effectively predict sudden cardiac arrest in pediatric hypertrophic cardiomyopathy?
Cohort
Do the HCM Risk-Kids and PRIMaCY genetic scoring systems effectively predict sudden cardiac arrest in pediatric hypertrophic cardiomyopathy?
Effect estimate: OR 10.2
In pediatric HCM, sarcomere gene variants strongly associate with SCA, and while current risk models predict follow-up SCA well, predicting initial SCA presentations remains a major clinical challenge.
Supports sarcomere variant testing for SCA risk stratification in pediatric HCM; leaves open whether genetic data refine existing prediction models.
Background: Sudden cardiac arrest (SCA) is a leading cause of death in pediatric hypertrophic cardiomyopathy (HCM). Objective: The study sought to analyze the clinical and genetic characteristics of pediatric HCM and assess the applicability of current SCA risk prediction models. Methods: We enrolled individuals diagnosed as HCM before 20 years of age, between 2000 and 2020, excluding those secondary to hemodynamic causes and those associated with genetic syndromes other than RASopathies. Results: scores compared with those who experienced SCA later during follow-up. Whole exome sequencing in 55 patients identified genetic pathogenic variants in 80% of cases. The most prevalent pathogenic variants were MYH7 (40%) and MYBPC3 (24%) within the sarcomere gene group, and RAF1 (36.8%) and PTPN11 (21.1%) among RASopathies. SCA events occurred mostly between 10 and 18 years of age. The SCA event-free survival rate was 84.2% by 10 years after diagnosis and associated with sarcomere gene pathogenic variants (odds ratio 10.2). Excluding the 6 patients presented as SCA initially, both the HCM Risk-Kids and PRIMaCY (precision medicine in cardiomyopathy) genetic scoring system exhibited strong predictive power for SCA during follow-up. Conclusion: In pediatric HCM, SCA is notably associated with sarcomere gene pathogenic variants. While newer risk scoring systems, if incorporated with genetic information, effectively predict SCA in this Asia cohort, a challenge remains: nearly half of SCA cases present as the initial clinical manifestation.
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Chiu et al. (2025) conducted a cohort in Pediatric hypertrophic cardiomyopathy. HCM Risk-Kids and PRIMaCY genetic scoring systems was evaluated on Sudden cardiac arrest (SCA) (OR 10.2). In pediatric hypertrophic cardiomyopathy, sudden cardiac arrest was strongly associated with sarcomere gene pathogenic variants (OR 10.2), with an 84.2% event-free survival rate at 10 years.
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