Abstract 9751: Combined Cardiomyopathy and Arrhythmia Genetic Testing Identifies Clinical Management Implications and Unexpected Results

Abstract

Introduction: Genetic testing for heritable cardiomyopathy and arrhythmia syndromes has evolved rapidly and is now recommended by cardiology professional societies to establish a genetic etiology, guide clinical management, and identify at-risk family members through cascade screening. However, the advantages of comprehensive, multi-condition gene panels versus condition-specific gene panels are debated. Objective: To assess the yield and clinical management implications of combined cardiomyopathy and arrhythmia genetic testing in a diverse cohort of patients referred for a suspected inherited cardiomyopathy or arrhythmia using a no-charge, sponsored genetic testing program. Methods: De-identified clinical histories and genetic test results were reviewed from a no-charge cardiomyopathy and arrhythmia genetic testing program. Up to 150 genes associated with cardiomyopathies and arrhythmias were evaluated, and positive findings were compared to provider diagnoses at the time of testing request. Results: In a cohort of 4,782 patients, a positive result (molecular diagnosis) was observed in 961 (20%). Of the positive results, 670/961 (70%) conferred clinical management implications, including genes associated with targeted therapy (6%; 57/961) or increased risk of ventricular arrhythmia (18%; 169/961). Positive results for 11% (75/691) of evaluable patients would have been missed by condition-specific panels based on clinician-provided diagnoses. Conclusions: Combined cardiomyopathy and arrhythmia genetic testing identified clinically-relevant variants for 1 in 5 patients suspected of a cardiomyopathy or arrhythmia. Over two-thirds of positive findings had clinical management implications. Combined disease testing captures >10% of patients who would be missed with condition-specific panels and this greater clinical utility may outweigh the burden of uncertain results.