Abstract
BACKGROUND: The aim of the study was to determine the prevalence of rare disease-causing variants in cardiomyopathy-associated genes in a cohort of patients with ischemic and non-ischemic dilated cardiomyopathy undergoing heart transplant. METHODS: We conducted a single-center cohort study of 60 adult patients with left ventricular ejection fraction ≤50% and left ventricular end-diastolic dimension ≥95th percentile for sex/height who underwent heart transplant between January 2017 and December 2023 and consented to participate in a cardiac tissue biobank. We evaluated the prevalence of rare (minor allele frequency <0.1%) disease-causing (pathogenic or likely pathogenic by American College of Genetics and Genomics criteria) variants in cardiomyopathy-associated genes. RESULTS: A total of 60 individuals fulfilled the inclusion criteria: 16 with ischemic dilated cardiomyopathy [88% men, median age 65 years, interquartile range (IQR) 64-68 years] and 44 with non-ischemic dilated cardiomyopathy (80% men, median age 53 years, IQR 39-65 years). We found that the prevalence of disease-causing variants was similar between patients with ischemic dilated cardiomyopathy (3/16 or 19%; 95% credible interval 6%-36%) and those with non-ischemic dilated cardiomyopathy (10/44 or 23%; 95% credible interval 12%-33%). Variants in the ischemic dilated cardiomyopathy group were found in the TTN and DMD genes. Variants in the non-ischemic dilated cardiomyopathy group were found in the TTN, FLNC, LMNA, MYH7, and RBM20 genes. CONCLUSIONS: Patients with ischemic dilated cardiomyopathy undergoing heart transplant possessed a similar burden of rare disease-causing variants as those with non-ischemic dilated cardiomyopathy. Our results suggest that genetic testing may be beneficial in patients with advanced heart failure requiring heart transplant due to ischemic dilated cardiomyopathy to detect disease-causing variants in cardiomyopathy-associated genes.