Abstract 15754: The Prevalence of Electronic Health Record-Based Clinical Phenotypes in Patients With Pathogenetic Variants Associated With Arrhythmogenic Right Ventricular Cardiomyopathy
Objective Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare myocardial disorder. Genetic etiology is ascribed to variants in 8 genes (PKP2, DSP, DSC2, DSG2, JUP, TMEM43, TGFβ2, RYR2). We aimed to establish the prevalence and clinical phenotype of individuals with pathogenic variants (PV) in these genes from an unselected cohort.
Methods Whole-exome sequences for 31,036 patients in the MyCode™ Biorepository were evaluated for pathogenic or likely pathogenic (P/LP) ARVC variants reported in ClinVar or the ARVC database. Composite ICD-9 data from the electronic health records of PV individuals vs a non-PV control group were analyzed.
Results 57 P/LP variants were identified in 240 individuals (0.77%), aged 61 ± 19 years. Characteristics of this PV group versus a non-PV control group are summarized in the table. Zero patients in the PV group had a documented diagnosis of ARVC. Use of implantable cardioverter defibrillators—the primary treatment for ARVC—was rare. Of individuals ≥55 years, 24% with PV had no history of cardiac disease (vs. 22% for non-PV). However, there was a modest increase in the prevalence of cardiac electrical abnormalities (e.g., tachycardia, fibrillation) in PV vs. non-PV. There was also a trend towards increased diagnoses of 'other primary cardiomyopathy'.
Conclusions The prevalence of reported pathogenic ARVC variants (0.77%) greatly exceeds the disease prevalence (0.02 - 0.10%). In this cohort of 240 genotype-positive subjects, there was little evidence of overt ARVC disease, suggesting that the positive-predictive value for classic ARVC in individuals with an incidental positive genetic finding is low. The increased risk of certain clinical findings, not specific to ARVC, supports the notion that the spectrum of phenotypes associated with pathogenic variants in these genes is broader than classically described. Targeted “deep phenotyping” is needed to assess subclinical phenotypes in genomically screened populations.
Author Disclosures: C.M. Haggerty: Ownership Interest; Modest; Regeneron Pharmaceuticals. S.A. Pendergrass: None. M. Barr: None. J.B. Leader: None. D.N. Hartzel: Ownership Interest; Modest; Regeneron Pharmaceuticals. M.D. Ritchie: None. D.J. Carey: None. D.H. Ledbetter: Consultant/Advisory Board; Modest; Natera, Inc.. M.S. Williams: None. F.E. Dewey: Employment; Significant; Regeneron Pharmaceuticals. A. Lopez: Employment; Significant; Regeneron Pharmaceuticals. J. Penn: Employment; Significant; Regeneron Pharmaceuticals. J.D. Overton: Employment; Significant; Regeneron Pharmaceuticals. J.G. Reid: Employment; Significant; Regeneron Pharmaceuticals. M.F. Murray: None. B.K. Fornwalt: None.
- © 2015 by American Heart Association, Inc.