Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study From the Pediatric Cardiomyopathy Registry

Kamsheh, AM; Ware, SM; Bhatnagar, S; Martin, LJ; Lee, TM; Towbin, JA; Kantor, PF; Lal, AK; Bansal, N; Ballweg, JA; Colan, SD; Aronow, BJ; Canter, CE; Lipshultz, SE

doi:10.1161/circheartfailure.125.013104

Heart failure & cardiomyopathies

Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study From the Pediatric Cardiomyopathy Registry

Circ Heart FailPublished 5 Dec 2025Cross-sectional study

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Authors' conclusion

Children with DCM secondary to myocarditis had a higher burden of variants in cardiomyopathy-associated genes than that of heart-healthy controls.

Study context

Population: Children with dilated cardiomyopathy (DCM) in the Pediatric Cardiomyopathy Registry who underwent exome sequencing

Exposure: DCM secondary to myocarditis vs heart-healthy controls
Myocarditis DCMn = 32
Controlsn = 128reference
Outcome: Prevalence of rare predicted-damaging variants in cardiomyopathy-associated genes

Methodological detailsmulticentre registry, matched controls (4:1 on genomic similarity)

Multicentre registry
Matched controls (4:1 on genomic similarity)

Main finding

As reported in the abstract

Rare predicted-damaging variants

Myocarditis DCM34.4%11 of 32

Controls6.3%8 of 128

P < 0.001

Observational data: associations, not effects.

Further findings

Outcome	Myocarditis DCM	Controls	P value
Clinical classification of rare predicted-damaging variants
Pathogenic	1/12	— not stated in the abstract
Likely pathogenic	3/12	— not stated in the abstract
Uncertain significance	8/12	— not stated in the abstract
Benign	— not stated in the abstract	2/8
Likely benign	— not stated in the abstract	4/8
Pathogenic/likely pathogenic variantsMyocarditis DCM vs Controls	12.5% (95% CI 3.5%–29.0%)	0% (95% CI 0%–2.3%)	P < 0.01

— not stated in the abstract

Myocarditis DCM vs DCM alone · rare predicted-damaging variants: P = 0.17
Myocarditis DCM vs DCM alone · pathogenic/likely pathogenic variants: P = 1.00

Myocarditis DCM vs DCM alone

Not significantly different

Original publication

Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study From the Pediatric Cardiomyopathy Registry. Circ Heart Fail. Published 5 December 2025. doi:10.1161/circheartfailure.125.013104

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