Abstract 4366533: York Trinity Score: An Anticipatory Risk Tool For Predicting Pathogenic Genotypes in Dilated Cardiomyopathy Phenotypes

Abstract

Background: Genetic testing enables early identification, and risk stratification for both probands and at-risk family members with dilated cardiomyopathy (DCM). Although clinical tools to predict positive gene test result (G+) have been proposed, none are routinely used. Objectives: To develop a clinical gene positivity risk tool based on a comprehensive, up-to-date, and anticipatory gene panel that targets DCM patients. Methods: Clinical, electrocardiogram, echocardiographic, and cardiac magnetic resonance (CMR) imaging variables were collected for 223 genotyped patients from a single US center with DCM. Independent predictors of G+ were identified using multivariable logistic regression and combined to form the York Trinity Gene Yield Score, which was formulated in both practical and computed versions. Results: 26% of the derivation cohort were G+ for a known DCM mutation. The York Trinity Score consists of three independent predictors of G+: T-wave inversion (OR: 2.21; 95% CI: 1.09-4.45; P = 0.027), absence of left bundle branch block (OR: 6.45; 95% CI: 2.45-16.99; P < 0.001), and the total number of segments with late gadolinium enhancement (OR: 1.25; 95% CI: 1.11-1.41; P < 0.001). Those variables yielded a G+ rate ranging from 5% when none of them were present (score 0), to 83.3% when all of them were present (score 3). Internal validation provided a C-statistic of 0.76 (95% CI: 0.70–0.82) for the computed version and 0.72 (95% CI: 0.65–0.78) for the practical version. Conclusion: The York Trinity Gene Yield Score is a promising tool with predictive performance for identifying pathogenic genotypes across broader DCM phenotypes.