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

• Published in: International journal of cardiology Vol. 393; p. 131405
• Main Authors: Boleti, Olga D., Roussos, Sotirios, Norrish, Gabrielle, Field, Ella, Oates, Stephanie, Tollit, Jennifer, Nepali, Gauri, Bhole, Vinay, Uzun, Orhan, Daubeney, Piers E.F., Stuart, Graham A., Fernandes, Precylia, McLeod, Karen, Ilina, Maria, Liaqath, Muhammad Najih Ali, Bharucha, Tara, Delle Donne, Grazia, Brown, Elspeth, Linter, Katie, Khodaghalian, Bernadette, Jones, Caroline, Searle, Jonathan, Mathur, Sujeev, Boyd, Nicola, Reindhardt, Zdenka, Duignan, Sophie, Prendiville, Terence, Adwani, Satish, Zenker, Martin, Wolf, Cordula Maria, Kaski, Juan Pablo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2023
• Subjects: Cardiomyopathy, Hypertrophic - complications; Cardiomyopathy, Hypertrophic - diagnosis; Child; Child, Preschool; Death, Sudden, Cardiac - epidemiology; Death, Sudden, Cardiac - etiology; Humans; Hypertrophic cardiomyopathy; Infant; Noonan syndrome; Pediatrics; RASopathies; Retrospective Studies; Risk Assessment; Risk Factors; Sudden cardiac death; Syncope; NSML; Pediatrics; LP; RV; NS; LV; RASopathies; CFCS; LVOT; RVOT; P; MLVWT; ANOVA; MACE; Noonan syndrome; LVOTO; NYHA; CCF; NSVT; NS-LAH; ICD; IQR; Sudden cardiac death; RVOTO; RA; CS; CV; HCM; LA; SCD; Hypertrophic cardiomyopathy; CHD; VT; LVH
• DOI: 10.1016/j.ijcard.2023.131405
• ISSN: 0167-5273; 1874-1754

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. [Display omitted] •Children with RASopathy associated hypertrophic cardiomyopathy (HCM) have a high risk for sudden cardiac death (SCD)•The HCM Risk-Kids risk prediction model used for children with non-syndromic HCM appears unsuitable for use in this cohort•Non-sustained ventricular tachycardia and unexplained syncope emerge as predictors of SCD•Larger collaborations are needed to validate these results and identify specific risk factors for SCD in this population