Key result
Thin filament variants carry ~3-fold higher SCD-MACE risk in pediatric HCM.
Why the study?
The clinical and genetic characteristics of Japanese pediatric HCM had not been comprehensively characterized, and the applicability of Western SCD risk prediction models such as HCM Risk-Kids and PRiMACY to Asian children remained uncertain.
Do established sudden cardiac death risk prediction models (HCM Risk-Kids, AHA, PRiMACY clinical, PRiMACY genetic) accurately predict SCD-related major adverse cardiovascular events in Japanese children with hypertrophic cardiomyopathy?
Cohort (n=141)
Yes
Do established sudden cardiac death risk prediction models (HCM Risk-Kids, AHA, PRiMACY clinical, PRiMACY genetic) accurately predict SCD-related major adverse cardiovascular events in Japanese children with hypertrophic cardiomyopathy?
In Japanese pediatric HCM, thin filament gene variants carry a higher risk of sudden cardiac death events, and the HCM Risk-Kids model provides both acceptable discrimination and superior calibration for risk stratification compared to PRiMACY clinical.
HCM Risk-Kids may aid SCD risk stratification in Japanese pediatric HCM; extends Western model validation to an Asian cohort.
Background Sudden cardiac death (SCD) is the leading cause of mortality in pediatric hypertrophic cardiomyopathy (HCM). Risk prediction models including HCM Risk-Kids and PRiMACY have been developed predominantly in Western populations, but their applicability to Asian children remains uncertain. The clinical and genetic characteristics of Japanese pediatric HCM have not been comprehensively characterized. Objectives To characterize the clinical and genetic features of Japanese pediatric HCM and externally validate established SCD risk prediction models. Methods This retrospective multicenter study enrolled 141 Japanese children with HCM from 35 hospitals (2013–2025). Clinical characteristics were compared between infantile-onset (<1 year) and childhood-onset groups, and between genetic subgroups. The primary outcome was SCD-related major adverse cardiovascular events (SCD-MACE). External validation of four risk models (HCM Risk-Kids, AHA, PRiMACY clinical, PRiMACY genetic) was performed. Results Infantile-onset HCM comprised 31.2% (n=44) of the cohort, substantially higher than typically reported in Western studies. Pathogenic variants were identified in 53.9%, predominantly in MYBPC3 (20.6%), MYH7 (15.6%), and other sarcomeric genes (17.7%). Genetic yield was significantly lower in infantile-onset (27.3%) versus childhood-onset patients (65.9%, P<0.001). Genotype-specific outcomes differed significantly (P=0.046): thin filament variant carriers had the highest SCD-MACE rate (32.0%) versus MYBPC3 (10.3%), MYH7 (9.0%), and variant-negative (10.7%). Variant-positive patients showed regression of septal hypertrophy Z-scores during follow-up, while variant-negative patients demonstrated stable hypertrophy. Over median 52-month follow-up, 20 patients (14.2%) experienced SCD-MACE, with 5-year and 10-year event-free survival of 91.2% and 79.8%. All four risk models demonstrated acceptable discrimination (AUC 0.69–0.74) without significant inter-model differences. HCM Risk-Kids showed adequate calibration (Hosmer-Lemeshow P=0.252, slope 1.105), while PRiMACY clinical demonstrated miscalibration (P=0.034). Unexplained syncope (HR 25.5, P<0.001) and NSVT (HR 13.3, P=0.035) were significant predictors. Conclusions Japanese pediatric HCM exhibits distinctive features including high infantile-onset proportion, lower genetic yield in infants, and elevated SCD risk with thin filament gene variants. Established risk models maintain acceptable discrimination, with HCM Risk-Kids demonstrating superior calibration for clinical application.
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Hirono et al. (2026) conducted a cohort in Pediatric hypertrophic cardiomyopathy (n=141). Thin filament gene variants and SCD risk prediction models (HCM Risk-Kids, AHA, PRiMACY) vs. MYBPC3, MYH7, and variant-negative subgroups was evaluated on Sudden cardiac death-related major adverse cardiovascular events (SCD-MACE) (p=0.046). Thin filament variants carried the highest SCD-MACE rate (32.0%, P=0.046) in Japanese pediatric HCM, while HCM Risk-Kids showed acceptable discrimination (AUC 0.69–0.74) and calibration (P=0.252).
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