Abstract 15108: Phenotypic Associations and Clinical Outcomes of Genetically Predicted Left Ventricular End Systolic Diameter in Prevalent Heart Failure

Abstract

Introduction: Varying degrees of systolic dysfunction after myocardial injury suggest a genetic basis for cardiac contractile reserve. Left ventricular end systolic dimension (LVESD), acquired by transthoracic echocardiography (TTE), is a proxy for cardiac contractility, and common variation underlying LVESD may offer insight into the underlying biology and clinical manifestations of heart failure (HF) and related phenotypes. Hypothesis: We hypothesized that elevations in genetically predicted LVESD would be associated with prevalent HF with reduced ejection fraction (HFrEF), but not HF with preserved ejection fraction (HFpEF), and with mortality among those with established HF. Methods: LVESD measurements (n = 7,630) were extracted for adults of European ancestry with available genome-wide genotyping who had also undergone clinically indicated TTE at Vanderbilt University Medical Center (VUMC). A polygenic risk score (PRS) for LVESD was created and validated in a separate cohort. HF status was defined using a validated algorithm. Logistic regressions were used to test for association of the PRS with prevalent HFrEF and HFpEF. Cox proportional hazards was used to test for association between PRS and incident death among (2,672) subjects with HF. All models were conducted in R and adjusted for age and sex. Results: A linear model of measured LVESD was significant for PRS (R^2 = 0.092, p < 0.001). The PRS was significantly associated with prevalent HFrEF (OR 1.15 per SD, p < 0.003) but not HFpEF. Genetically predicted LVSD was not associated with mortality among patients with HF (OR 1.01, p = 0.83). Conclusions: Genetically predicted LVESD, assessed by PRS, was associated with risk of prevalent HFrEF but not HFpEF. LVESD PRS was not associated with incident death in subjects with overall HF. These results suggest a potential role of LVSD PRS in HFrEF risk stratification, and further research should explore the relationship between LVESD PRS and incident HF.