Effect of Genotype on Myocardial Strain in Phenotype-Negative Individuals at Genetic Risk for Arrhythmogenic Cardiomyopathy

Motivation: Arrhythmogenic cardiomyopathy is a leading cause of sudden cardiac death in individuals <35 years of age and is frequently unrecognized prior to a sudden death event. Genomic screening may identify at-risk individuals early, yet risk of future events is unknown, and biomarkers of early dysfunction/arrhythmia development are lacking. Goal(s): Quantify the association between genetic risk and myocardial structure or function in individuals with pathogenic/likely pathogenic arrhythmogenic cardiomyopathy-associated variants identified through secondary findings of genomic sequencing. Approach: Assessment of myocardial tissue maps, strain, torsion, and dyssynchrony will be compared between genotype-positive cases and matched genotype-negative controls, both without cardiovascular disease, using DENSE-MRI. Impact: The results of this study will help inform patients and providers in the management of genomic screening-identified genetic risk for arrhythmogenic cardiomyopathy by identifying potential biomarkers of nascent disease development, which may prompt early intervention to reduce mortality.