Elsevier

International Journal of Cardiology

Volume 371, 15 January 2023, Pages 516-522
International Journal of Cardiology

Clinical profile and outcome of cardiomyopathies in infants and children seen at a tertiary centre

https://doi.org/10.1016/j.ijcard.2022.09.034Get rights and content

Highlights

  • Children with CMP with infantile onset and with a metabolic etiology had the worst prognosis.

  • MACE is most commonly associated with DCM, inborn errors of metabolism and genetic syndromes.

  • NGS genetic testing was pivotal to reach an etiological diagnosis and guide management.

Abstract

Introduction

Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade.

Patients and methods

We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded.

Results

We enrolled 110 patients (65 males), diagnosed at a median age of 27 [4–134] months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases.

Conclusions

In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management.

Introduction

Cardiomyopathies (CMPs) in children are rare entities, characterized by greater etiological and clinical heterogeneity compared to adult populations. Causes in pediatric patients include genetic, neuromuscular and metabolic diseases, coronary artery abnormalities, tachyarrhythmias, myocarditis and toxic agents; in a sizeable subset of children with “idiopathic” disease, no clear cause can be identified [1,2]. In these age groups, the possibility to identify the molecular defect by genetic testing is lower than at older other ages [14].

Inherited pediatric cardiomyopathies have a complex and heterogeneous background [3]. Genetic testing is widely employed, exploiting constant technical and cultural progress in the field, and may be key in reaching a final diagnosis as well as in guiding cascade family screening. Increasingly, genetic results are being used in predicting long-term outcome [4]. However, genotype-phenotype correlations are often elusive, and the natural history of pediatric cardiomyopathies remains poorly understood due to paucity of longitudinal data, calling for further research as novel therapeutic options, including gene therapy, are emerging [2]. Aim of this study was therefore to recapitulate the clinical, genetic and phenotypic correlates of children with cardiomyopathies consecutively referred to a tertiary care pediatric center, and to assess the relevance of presenting features in predicting risk of cardiovascular events during follow up.

Section snippets

Patient selection

We retrospectively reviewed 110 patients with pediatric-onset cardiomyopathy referred to the Cardiology Department of Meyer Children's Hospital, a tertiary care children hospital in Florence, Italy, between January 2008 and December 2019. This study included all consecutive patients aged ≤18 years referred for cardiovascular, genetic and metabolic screening who had at least two clinical visits or a baseline visit and a remote/telephone follow up >1 year apart. All patients with metabolic

Baseline clinical characteristics

The 110 patients (45 females, 40.9%) were diagnosed at a median age of 27 [4–134] months. Overall, 38 (35%) had an infant onset (<1 year of life), while the remaining 72 children (65%) were older than 1 year (Table 1). Phenotypes were evenly distributed among infant and childhood onset patients with a predominance of HCM (46.4%). Overall, 48 patients (43.6%) were diagnosed with HCM, 35 (31.8%) with DCM, 12 (10.9%) with LVNC, 3 (2.7%) with RCM, 7 (6.3%) mixed (3 HCM/LVNC, 2 HCM/RCM, 2 DCM/LVNC)

Discussion

In this retrospective study, we analysed 110 patients who received a diagnosis of pediatric cardiomyopathy under the age of 18, of whom about one third (35%) had an infant onset (<1 year of age). HCM was the most represented phenotype, accounting for 44% of the total; consistently, mutations in sarcomere protein genes and metabolic diseases were the most common etiologies, accounting for 31% and 32% of the total, respectively. About one third of patients had evidence of familial transmission of

Conclusions

In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Hypertrophic cardiomyopathy showed less severe prognosis compared to other phenotypes, even though arrhythmic complications were significant. Dilated cardiomyopathy, genetic syndromes and inborn errors of metabolism

Disclosure

None.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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