PO34 Similar genetic yield but distinct gene patterns in paediatric heart failure due to dilated cardiomyopathy and myocarditis

Abstract Background In children, frequent causes of severe heart failure include dilated cardiomyopathy (DCM) and myocarditis. Although considered distinct entities, myocarditis can present with a dilated cardiomyopathy phenotype (MycDCM) (1). In DCM, genetic variants are detected in 30–40% of patients, with a heterogeneous spectrum. Sarcomere genes appear most frequently in primary DCM, whereas the genetic architecture of MycDCM is less well characterized (2). Regarding outcome, children with MycDCM have been reported to experience worse event-free survival compared with those with primary DCM (3). Purpose To compare the genetic spectrum and outcomes of paediatric DCM with (MycDCM) and without biopsy-proven myocarditis (DCM). Methods We retrospectively analysed 138 paediatric patients with DCM at our centre (2013–2023). Genetic testing was performed using cardiomyopathy gene panels, whole exome sequencing (WES) or genome sequencing (WGS). Variants were classified according to ACMG guidelines, and only likely pathogenic/pathogenic (LP/P) were included in further analyses. Children with syndromic diseases were excluded. Myocarditis was confirmed by endomyocardial biopsy. Results All 138 patients underwent genetic testing (n=78 WES/WGS; n=60 panel). Eighty-one (59%) were diagnosed with DCM, 57 (41%) had MycDCM. LP/P variants were detected in 34 patients overall, including 21/81 (26%) in the DCM group and 13/57 (23%) in the MycDCM group. In the DCM group, median age at symptom onset was 0.4 years (IQR 0.0–10.3), 13 (62%) were female. Sarcomere genes predominated with 71% (15/21): TNNT2 (n=4), TNNI3 (n=3), TPM1 (n=3), MYBPC3 (n=2), MYH7, ACTC1, ACTN2 (n=1, respectively). In MycDCM, median age at onset was 3.1 years (IQR 0.5–8.4), 7 (54%) were female. Variants included genes linked to cytoskeletal integrity and inflammation (BAG3, LMNA n=2; FLNC, DES n=1) about half were sarcomere variants (54%; 7/13): TNNT2, TNNI3, TTN n=2, respectively; MYH7 n=1. Heart transplantation was performed in 11/21 (52%) DCM and 9/13 (69%) MycDCM patients. Three patients with DCM died, whereas no deaths occurred in MycDCM. One MycDCM patient with ventricular assist device support was successfully weaned. Four patients were lost to follow-up. Conclusions In paediatric patients with primary DCM, LP/P variants were detected at the same proportion as in those with DCM and biopsy-proven myocarditis. Children with primary DCM were younger at symptom onset and predominantly carried sarcomere gene variants, whereas MycDCM more often harboured variants in genes linked to inflammation. This underscores the importance of in-depth phenotyping and integrated genetic testing to guide diagnosis and management in paediatric heart failure.