Clinical presentation and survival of childhood hypertrophic cardiomyopathy: a retrospective study in United Kingdom

Abstract

AimsUnderstanding the spectrum of disease, symptom burden and natural history are essential for the management of children with hypertrophic cardiomyopathy (HCM). The effect of changing screening practices over time has not previously been studied. This study describes the clinical characteristics and outcomes of childhood HCM over four decades in a well-characterized United Kingdom cohort.Methods and resultsSix hundred and eighty-seven patients with HCM presented at a median age of 5.2 years (range 0–16). Aetiology was: non-syndromic (n = 433, 63%), RASopathy (n = 126, 18.3%), Friedreich’s ataxia (n = 59, 8.6%) or inborn errors of metabolism (IEM) (n = 64, 9%). In infants (n = 159, 23%) underlying aetiology was more commonly a RASopathy (42% vs. 11.2%, P < 0.0001) or IEM (18.9% vs. 6.4% P < 0.0001). In those with familial disease, median age of presentation was higher (11 years vs. 6 years, P < 0.0001), 141 (58%) presented <12 years. Freedom from death or transplantation was 90.6% (87.9–92.7%) at 5 years (1.5 per 100 patient years) with no era effect. Mortality was most frequently sudden cardiac death (SCD) (n = 20, 2.9%). Children diagnosed during infancy or with an IEM had a worse prognosis (5-year survival 80.5% or 66.4%). Arrhythmic events occurred at a rate of 1.2 per 100 patient years and were more likely in non-syndromic patients (n = 51, 88%).ConclusionThis national study describes a heterogeneous disease whose outcomes depend on the age of presentation and aetiology. Overall mortality and SCD rates have not changed over time, but they remain higher than in adults with HCM, with events occurring in syndromic and non-syndromic patients.

A validation study of the European Society of Cardiology guidelines for risk stratification of sudden cardiac death in childhood hypertrophic cardiomyopathy

“…From the total cohort of 687 patients, 8 411 patients had non-syndromic HCM, diagnosed aged 16 years or younger, and without a previous history of sustained ventricular tachycardia or aborted cardiac arrest ( Figure 1 ). Baseline clinical characteristics are shown in Table 1 .…”

“…Childhood HCM is recognized to be a heterogeneous disease 5 , 6 . In our UK cohort, 37% of patients had either a RASopathy syndrome, neuromuscular disease, or inborn error of metabolism, and age of diagnosis ranged from 1 to 16 years of age 8 . Current guidelines do not account for this heterogeneity, providing relative risks for an arrhythmic event for non-homogenous groups rather than individualized estimates.…”

“…Relatively little is known about the sample size requirements for external validation of prediction models, although a sample containing at least 100 events and 100 non-events has been suggested 21 . Using published rates of arrhythmic events in childhood HCM of 1.5/100 patient years 8 with a median follow-up of 5 years, this would require over 1300 patients assuming no dropout during the 5-year follow-up period. Such a sample size would be challenging to achieve for a rare condition with a reported prevalence of childhood HCM below 3/100 000.…”

“…The diagnosis of HCM was made in the presence of left ventricular wall thickness >2 SD above the body surface area (BSA)-corrected population mean ( z -score ≥+2), which could not be solely explained by abnormal loading conditions 9 . Data on the clinical presentation and survival of the entire cohort have been recently published 8 . In the present study, patients with a history of sustained ventricular arrhythmias or aborted SCD were excluded from analysis, as they meet criteria for secondary prevention ICD implantation.…”

The adolescent athlete's heart; A miniature adult or grown‐up child?

“…28 The complex interaction between growth, training, gender and maturity is also true and must be taken into account when assessing , where a clear prepubertal phenotype is more difficult to recognize than in adult life. 31 For children with a family history of HCM, 1 to 2 yearly screening is recommended from aged 10 years 32 as presentation can occur in childhood. 33 These factors make the assessment of normality of cardiac size and function challenging, and during childhood, cardiac chamber sizes should be referenced to somatic size using z scores or relating cardiac dimensions to height or body surface area.…”