Key result
DCM phenotype in pediatric myocarditis is linked to ~53-point lower 5-year event-free survival.
Why the study?
Myocarditis is a common cause of pediatric heart failure with a postulated genetic background, prompting evaluation of clinical and genetic characteristics to predict outcome in patients 18 years of age or younger.
Does the presence of a DCM phenotype predict worse clinical outcomes and genetic variant burden in pediatric patients with myocarditis?
Cohort (n=42)
Does the presence of a DCM phenotype predict worse clinical outcomes and genetic variant burden in pediatric patients with myocarditis?
Pediatric myocarditis patients presenting with a DCM phenotype have a higher burden of pathogenic cardiomyopathy variants and a significantly worse outcome, warranting targeted genetic evaluation.
Answers are grounded in this paper and cite their sources.
DCM phenotype may flag higher-risk pediatric myocarditis for closer surveillance; leaves open whether genetic testing improves stratification.
Background: Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome. Methods: A cohort of 42 patients (Genetics in Pediatric Myocarditis) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. Genetics in Pediatric Myocarditis patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (myocarditis without phenotype of DCM) and 20 patients with DCM (myocarditis with phenotype of DCM). Results: Myocarditis with phenotype of DCM patients (median age 1.4 years) were younger than myocarditis without phenotype of DCM patients (median age 16.1 years; P <0.001) and were corresponding to heart failure–like and coronary syndrome–like phenotypes, respectively. At least one likely pathogenic/pathogenic variant was identified in 9 out of 42 patients (22%), 8 of them were heterozygous, and 7 out of 9 were in myocarditis with phenotype of DCM. Likely pathogenic/pathogenic variants were found in genes validated for primary DCM ( BAG3, DSP, LMNA, MYH7, TNNI3, TNNT2 , and TTN ). Rare variant enrichment analysis revealed significant accumulation of high-impact disease variants in myocarditis with phenotype of DCM versus healthy individuals ( P =0.0003). Event-free survival was lower ( P =0.008) in myocarditis with phenotype of DCM patients compared with myocarditis without phenotype of DCM and primary DCM. Conclusions: We report heterozygous likely pathogenic/pathogenic variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of likely pathogenic/pathogenic variants, and poor outcome. These phenotype-specific and age group–specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.
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Seidel et al. (2021) conducted a cohort in Pediatric biopsy-proven myocarditis (n=42). Phenotype of dilated cardiomyopathy (DCM) vs. Without phenotype of DCM was evaluated on Combined end point of mechanical circulatory support, heart transplantation, or death at 5 years (p=0.008). Presentation with a dilated cardiomyopathy phenotype in pediatric myocarditis was associated with significantly lower 5-year event-free survival compared to presentation without a DCM phenotype (32% vs 85%, p=0.008).
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