Genetic Variants Associated With Worse Outcomes in Pediatric Cardiomyopathy

Researchers call for universal generic testing

Previous research in pediatric cardiomyopathy has focused on causative pathogenic variants but hasn’t demonstrated consistent genotype-outcome findings, according to Danielle Burstein and her colleagues who presented research findings at the American Heart Association Scientific Sessions meeting in Philadelphia in November. Variants of unknown significance (VUS), they say, may represent important genetic modifiers that influence outcomes. AHA15273  

Burstein and her coinvestigators hypothesized that greater genetic variant burden (pathogenic or of unknown significance) correlated with worse outcomes in pediatric cardiomyopathy. In their study, 420 children aged infant to 13 years old underwent multigene testing between 2010 and 2018. The composite endpoint was freedom from major adverse cardiac event.

Across all types of cardiomyopathy, the presence of pathogenic variants alone was insufficient to predict outcome, but increased VUS burden was associated with worse outcomes in dilated cardiomyopathy and hypertrophic cardiomyopathy. VUS in addition to pathogenic variants was associated with MACE across all CM subtypes.

The researchers say their findings highlight the need for universal genetic testing to improve genetic risk stratification models for prognosis and potential therapy.