External validation of the HCM Risk-Kids model for predicting sudden cardiac death in childhood hypertrophic cardiomyopathy

Abstract

Aims Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualized estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort. Methods and results A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1–16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twenty-three patients (5.4%) met the SCD end-point within 5 years, with an overall incidence rate of 2.03 per 100 patient-years [95% confidence interval (CI) 1.48–2.78]. Model validation showed a Harrell’s C-index of 0.745 (95% CI 0.52–0.97) and Uno’s C-index 0.714 (95% 0.58–0.85) with a calibration slope of 1.15 (95% 0.51–1.80). A 5-year predicted risk threshold of ≥6% identified 17 (73.9%) SCD events with a corresponding C-statistic of 0.702 (95% CI 0.60–0.81). Conclusions This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of ≥6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualized risk predictions and shared decision-making in children with HCM.

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy

“… 4 As sudden death is a rare event, a composite definition of life-threatening arrhythmias was used for this study, which includes appropriate ICD therapies. This is in keeping with previous studies in adults and children with HCM, 11 , 27 , 36 , 39 but it is plausible that not all appropriate therapies would have necessarily resulted in sudden death untreated. Genetic testing was not performed systematically in this cohort, therefore it is beyond the scope of this study to investigate the yield of genetic testing in preadolescent nonsyndromic HCM.…”

Indications and management of implantable cardioverter-defibrillator therapy in childhood hypertrophic cardiomyopathy

“…A large-scale external validation study of HCM Risk-Kids was reported in 2022, confirming the ability of the model with a threshold of >6% risk at 5 years to identify over 70% of children with a major arrhythmic event and a C-statistic of 0.75. 93 Additional external validation was provided from a national cohort, in which similar performance was observed (C-statistic 0.69, sensitivity 73%, positive predictive value 22%, and negative predictive value 95%). 47 In this study, using data from ≥7 years of age in patients with a diagnosis in infancy improved the C-statistic to 0.76, and combining HCM Risk-Kids score with electrocardiogram risk score improved specificity and C-statistic compared with either measure alone.…”

Treatment Strategies for Cardiomyopathy in Children: A Scientific Statement From the American Heart Association

“…Norrish et al 109 have reported the HCM Risk-Kids risk prediction model, which is based on unexplained syncope, degree of hypertrophy, left atrial diameter, and nonsustained supraventricular tachycardia in a cohort of 421 patients 1 to 16 years of age. If all 4 risk factors were present, the 5-year risk of experiencing the composite end point was ≈10%.…”