Sudden cardiac death (SCD) is the most common mode of death outside of infancy in childhood hypertrophic cardiomyopathy (HCM),^1,2 with higher annual rates compared with those in adults with the disease.³ Current practice guidelines recommend primary prevention implantable cardioverter defibrillators (ICDs) in children based on the presence of clinical risk factors for SCD extrapolated mostly from observational adult studies,^4,5 but this approach poorly discriminates risk in both adult and pediatric populations.^6,7 A clinical risk tool (HCM Risk-SCD) that estimates the 5-year risk of SCD was developed⁸ and validated in adults with HCM.^9-12 The aim of this study was to develop a similar pediatric SCD risk model using a large, international cohort and compare its performance with the adult model.

Childhood-onset cardiomyopathies are rare and poorly characterized. This study examined the baseline characteristics and 1-year follow-up of children with cardiomyopathy in the first European Cardiomyopathy Registry. Prospective data were collected on individuals aged 1–<18 years enrolled in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis long-term registry (June 2014–December 2016). A total of 633 individuals aged ≤18 years with hypertrophic [HCM; n = 388 (61.3%)], dilated [DCM; n = 206 (32.5%)], restrictive [RCM; n = 28 (4.4%)], and arrhythmogenic right ventricular cardiomyopathy [ARVC; n = 11 (1.7%)] were enrolled by 23 referral centres in 14 countries. Median age at diagnosis was 4.0 [interquartile range (IQR) 0–10] years, and there was a male predominance [n = 372 (58.8%)] across all subtypes, with the exception of DCM diagnosed <10 years of age; 621 (98.1%) patients were receiving cardiac medication and 80 (12.6%) had an implantable cardioverter-defibrillator. A total of 253 patients (253/535, 47.3%) had familial disease. Genetic testing was performed in 414 (67.8%) patients with a pathogenic or likely pathogenic variant reported in 250 (60.4%). Rare disease phenocopies were reported in 177 patients (28.0%) and were most frequent in patients under 10 years [142 (30.9%) vs. 35 (19.6%); P = .003]. Over a median follow-up of 12.5 months (IQR 11.3–15.3 months), 18 patients (3.3%) died [HCM n = 9 (2.6%), DCM n = 5 (3.0%), RCM n = 4 (16.0%)]. Heart failure events were most frequent in RCM patients (36.0%). The findings confirm the heterogeneous aetiology of childhood cardiomyopathies and show a high frequency of familial disease. Outcomes differed by cardiomyopathy subtype, highlighting a need for disease-specific evaluation and treatment. Characteristics and outcomes of paediatric onset cardiomyopathy in a European population. HCM, hypertrophic cardiomyopathy; DCM, dilated cardiomyopathy; RCM, restrictive cardiomyopathy; ARVC, arrhythmogenic right ventricular cardiomyopathy.

In hypertrophic cardiomyopathy (HCM), the following five risk factors have a major role in the primary prevention of sudden death (SD): family history of SD (FHSD), syncope, massive wall thickness (MWTh) >30 mm, non-sustained ventricular tachycardia (nsVT) in Holter monitoring of electrocardiography, and abnormal blood pressure response to exercise (aBPRE). In HCM, as a genetic cardiac disease, the risk for SD may also exist from birth. The aim of the study was to compare the survival curves constructed for each of the five risk factors in a traditional follow-up model (started at the first presentation of a patient at the institution) and in a novel follow-up model (started at the date of birth). In an additional analysis, we compared the survival rate in three subgroups (without FHSD, with one SD, and with two or more SDs in a family). A total of 1306 consecutive HCM patients (705 males, 601 females, mean age of 47 years, and 193 patients were <18 years) evaluated at 15 referral centres in Poland were enrolled in the study. In a novel method of follow-up, all the five risk factors confirmed its prognostic power (FHSD: P = 0.0007; nsVT: P < 0.0001; aBPRE: P = 0.0081; syncope: P < 0.0001; MWTh P> 0.0001), whereas in a traditional method, only four factors predicted SD (except aBPRE). In a novel model of follow-up, FHSD in a single episode starts to influence the prognosis with a delay to the fifth decade of life (P = 0.0007). Multiple FHSD appears to be a very powerful risk factor (P < 0.0001), predicting frequent SDs in childhood and adolescence. The proposed concept of a lifelong calculated follow-up is a useful strategy in the risk stratification of SD. Multiple FHSD is a very ominous risk factor with strong impact, predicting frequent SD episodes in the early period of life.

To date limited data are available to predict the progression to end-stage heart failure (HF) with subsequent death (non-SCD), need for heart transplantation, or sudden cardiac death (SCD) in children with hypertrophic cardiomyopathy (HCM). We aimed to determine predictors of long-term outcome in children with HCM. A total of 112 children (median 14.1, IQR 7.8–16.6 years) were followed up for the median of 6.5 years for the development of morbidity and mortality, including arrhythmic and HF-related secondary end points. HF end point included HF-related death or heart transplant, and arrhythmic end point included resuscitated cardiac arrest, appropriate ICD discharge, or SCD. Overall, 23 (21 %) patients reached the pre-defined composite primary end point. At 10-year follow-up, the event-free survival rate was 76 %. Thirteen patients (12 %) reached the secondary arrhythmic end point, and 10 patients (9 %) reached the secondary HF end point. In multivariate model, prior cardiac arrest (r = 0.658), QTc dispersion (r = 0.262), and NSVT (r = 0.217) were independent predictors of the arrhythmic secondary end point, while HF (r = 0.440), LV posterior wall thickness (r = 0.258), LA size (r = 0.389), and decreased early transmitral flow velocity (r = 0.202) were all independent predictors of the secondary HF end point. There are differences in the risk factors for SCD and for HF-related death in childhood HCM. Only prior cardiac arrest, QTc dispersion, and NSVT predicted arrhythmic outcome in patients aged <18 years. LA size, LV posterior wall thickness, and decreased early transmitral flow velocity were strong independent predictors of HF-related events.

Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.