Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: Validation of the HCM risk-kids model and predictors of events.

Hypertrophic cardiomyopathy Noonan syndrome Pediatrics RASopathies Sudden cardiac death

Journal

International journal of cardiology

ISSN: 1874-1754

Titre abrégé: Int J Cardiol

Pays: Netherlands

ID NLM: 8200291

Informations de publication

Date de publication:
15 Dec 2023

Historique:

received: 12 07 2023

revised: 09 09 2023

accepted: 27 09 2023

pubmed: 1 10 2023

medline: 1 10 2023

entrez: 30 9 2023

Statut: ppublish

Résumé

RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated. To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population. Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters. Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis. Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further.

Sections du résumé

BACKGROUND BACKGROUND

AIM OBJECTIVE

To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population.

METHODS METHODS

Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters.

RESULTS RESULTS

Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis.

CONCLUSION CONCLUSIONS

Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further.

Identifiants

DOI: 10.1016/j.ijcard.2023.131405 PMID: 37777071

pubmed: 37777071

pii: S0167-5273(23)01398-0

doi: 10.1016/j.ijcard.2023.131405

pii:

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

131405

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of Competing Interest Wolf CM: consultancy with Day One Biopharmaceuticals, Inc., BioMarin Pharmaceuticals, Adrenomed AG, and Pliant Therapeutics; ownership interest: Preventage Therapeutics. Zenker M: consultancy with Day One Biopharmaceuticals, Inc. and Novo Nordisk.