Abstract 4140148: Genetic Influence in Patients Transplanted for Myocarditis in the TOPMed-TOPCHeF Cohort of Explanted Hearts

Background: Myocarditis is a leading cause of secondary cardiomyopathy and stems from infection, medications, or immune etiologies. Recent reports identify an overlap between myocarditis and pathogenic / likely pathogenic (P/LP) genetic variants of dilated and arrhythmogenic cardiomyopathies (DCM/ACM). Hypothesis: We hypothesized that myocarditis leading to heart failure and transplantation could be influenced by P/LP mutations for DCM/ACM. Aims: To evaluate the impact of genetics in myocarditis, we investigated a series of patients presenting with symptoms consistent with myocarditis who were found to have P/LP genetic signatures for dilated and arrhythmogenic cardiomyopathies DCM/ACM. Methods: Patients with myocarditis, defined by retrospective clinical diagnosis, were selected from the NHLBI Trans-Omics for Precision Medicine (TOPMed) - Trans-Omics for Precision Medicine for Congestive Heart Failure (TOPCHeF) cohort. After informed consent, patients’ explanted hearts were collected in the University of Colorado Heart Tissue Bank. A total of 837 hearts (697 failing and 140 control hearts) underwent whole genome DNA sequencing (WGS). Results: 11 patients had a diagnosis of myocarditis based on clinical history. None had acute myocarditis at time of transplantation. P/LP variants in DCM/ACM genes were found in 6 patients. The average age at transplantation was 42.8 years for patients with genetic variants and 38.9 without. Demographics are included in table 1. The most common genetic variants were Titin truncations. Full genetic data are included in table 2. Conclusion: 50% of patients undergoing transplantation with a clinical diagnosis of myocarditis in the TOPMed-TOPCHeF population had P/LP variants in DCM/ACM genes. This underscores the importance of genetic testing in patients with a clinical presentation of myocarditis for future management implications.