Abstract 14343: Early Genetic Screening and Cardiac Intervention in Patients With Genetic Cardiomyopathies Within a Multidisciplinary Care Model

Abstract

Introduction: Patients with genetic cardiomyopathies are a heterogeneous group of patients who experience significant morbidity and mortality. Early cardiac assessment and intervention coupled with access to genetic counselling and testing may improve clinical outcomes and prevent progression to end-stage heart failure. Methods: Our prospective cohort study was conducted at our multidisciplinary Cardiomyopathy Clinic and patients with suspected genetic cardiomyopathy (CM) or a family history of CM ( n =405) were recruited. Patients with genetic analysis completed ( n =228) were categorized into dilated cardiomyopathy (DCM) ( n= 118), hypertrophic cardiomyopathy (HCM) ( n= 55), infiltrative cardiomyopathy (CM) ( n= 18), and Stage A/at-risk for CM ( n= 37). Continuous variables were analyzed using Wilcoxon signed-rank test or paired t test, while categorical variables were compared using Pearson chi-square tests. Results: There was a median follow-up time of 13 months (IQR: 7 - 21 months) with an increase in genetic testing, cascade family screening, optimization of guideline-directed medical therapy, and usage of device therapies compared to prior to clinic enrolment. In patients with genetic testing, 29.4% ( n= 67) had positive genotypes (pathogenic or likely pathogenic variants), 11.8% ( n= 27) had variants of unknown significance (VUS), and 58.8% ( n= 134) had negative or inconclusive genotypes. Optimization of medical and device therapies resulted in improvements in left ventricular ejection fraction from 30.5% (20.8 - 42.5%) to 45.5% (34.0 - 48.5%, P< 0.001), reduced left ventricular mass index from 121.2 g/m 2 (116.2 - 146.4 g/m 2 ) to 107.0 g/m 2 (88.9 - 134.7 g/m 2 , P< 0.001), and reduced E/e’ ratio from 12.6 cm/s (9.2 - 15.3 cm/s) to 10.9 cm/s (9.0 - 14.2 cm/s, P= 0.015). These improvements were driven by patients with negative genotypes (no variants or VUS) relative to those with positive genotypes. Additionally, patients with normal blood pressure (SBP < 120 mmHg and DBP < 80 mmHg) at follow-up had improvement in LVEF ( P< 0.001) and LVMI ( P= 0.005). Conclusion: Our findings demonstrate the efficacy of a combined cardiovascular genetics clinic in improving the clinical trajectories of patients with genetic cardiomyopathies.