Clinical presentation and long‐term outcomes of infantile hypertrophic cardiomyopathy: a European multicentre study

Abstract

AimsChildren presenting with hypertrophic cardiomyopathy (HCM) in infancy are reported to have a poor prognosis, but this heterogeneous group has not been systematically characterized. This study aimed to describe the aetiology, phenotype, and outcomes of infantile HCM in a well-characterized multicentre European cohort. Methods and resultsOf 301 children diagnosed with infantile HCM between 1987 and 2019 presenting to 17 European centres [male n = 187 (62.1%)], underlying aetiology was non-syndromic (n = 138, 45.6%), RASopathy (n = 101, 33.6%), or inborn error of metabolism (IEM) (n = 49, 16.3%). The most common reasons for presentation were symptoms (n = 77, 29.3%), which were more prevalent in those with syndromic disease (n = 62, 61.4%, P < 0.001), and an isolated murmur (n = 75, 28.5%). One hundred and sixty-one (53.5%) had one or more co-morbidities. Genetic testing was performed in 163 (54.2%) patients, with a disease-causing variant identified in 115 (70.6%). Over median follow-up of 4.1 years, 50 (16.6%) underwent one or more surgical interventions; 15 (5.0%) had an arrhythmic event (6 in the first year of life); and 48 (15.9%) died, with an overall 5 year survival of 85%. Predictors of all-cause mortality were an underlying diagnosis of IEM [hazard ratio (HR) 4.4, P = 0.070], cardiac symptoms (HR 3.2, P = 0.005), and impaired left ventricular systolic function (HR 3.0, P = 0.028). Conclusions This large, multicentre study of infantile HCM describes a complex cohort of patients with a diverse phenotypic spectrum and clinical course. Although overall outcomes were poor, this was largely related to underlying aetiology emphasizing the importance of comprehensive aetiological investigations, including genetic testing, in infantile HCM.

Natural History of Hypertrophic Cardiomyopathy in Noonan Syndrome With Multiple Lentigines

“…Prediction of clinical outcomes for patients with HCM is challenging because of the substantial heterogeneity of the population, particularly in children. Several registries have investigated the outcomes for HCM with different etiologies [18][19][20][21][22] and demonstrated that patients with RASopathies carry a higher risk of death or heart transplantation compared with idiopathic or sarcomeric HCM. Wilkinson et al 21 reported that patients with NS and HCM have a worse risk profile at presentation compared with other children with HCM, resulting in a 1-year mortality of 22%.…”

Pediatric Hypertrophic Cardiomyopathy: Exploring the Genotype‐Phenotype Association

“…Infants with pathologic hypertrophy are often associated with inborn errors of metabolism, which confers a significantly increased risk of death. 19 It could be possible that variants in pathways associated with metabolic disorders could be another example. In addition, genetic variants of α‐protein kinase 3 have been implicated as a pediatric cardiomyopathy gene.…”

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

“…Presentation in infancy (<1 year of age) was associated with an increased risk of cardiovascular death 5,6,8,83,84 ; however, the cause of death in this subgroup is most commonly associated with congestive heart failure and non-cardiovascular causes, rather than sudden cardiac death. 85 One study reported an increased risk of sudden cardiac death or malignant arrhythmia occurring in children above 13 years of age, 24 and a population-based study showed that 8-16-year-olds had a significantly higher mortality rate in sudden cardiac death than 17-30-year-olds, with the highest rate between the ages of 9 and 14 years. 44 Maurizi et al 22 evaluated 100 hypertrophic cardiomyopathy patients from 1 to 16 years old at diagnosis to describe the long-term outcome of paediatric onset hypertrophic cardiomyopathy and to identify agespecific arrhythmic risk factors.…”