Abstract 11916: Circulating Concentrations of Orexin A Predict Left Ventricular Myocardial Remodeling

Introduction: Left ventricular reverse remodeling (LVRR) may occur with guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF); LVRR is associated with better outcome in this setting. Molecular factors predictive of LVRR are not well understood. Background: Recent data suggest the minor allele for rs7767652 (upstream to the hypocretin/orexin receptor-2 [ HCRTR2 ] gene) is inversely associated with likelihood for LVRR after GDMT. Infusion of orexin A (the HCRTR2 receptor ligand) was protective against LV remodeling. Hypothesis: Concentrations of circulating orexin A predict LV remodeling in HFrEF (left ventricular ejection fraction [LVEF] Methods: We measured concentrations of orexin A in 113 HFrEF patients at baseline and at 10 months. Patients underwent echocardiography at the same time points. Measures of LV remodeling included LV end-diastolic and end-systolic volume index (LVEDVi, LVESVi) and LVEF. Results: As a function of the median baseline orexin A concentration of 1.04 ng/mL, there was no difference between groups in baseline characteristics, and no difference in concentrations of other prognostic biomarkers. Subjects with baseline orexin A ≥ 1.04 ng/mL had significantly greater reduction in LVEDVi and LVESVi and a trend towards greater improvement in LVEF at 10 months. Significantly fewer subjects with a baseline Orexin A concentration ≥ 1.04 ng/mL had increase in LVEDVi or LVESVi at study completion ( Table ). In binomial regression adjusted for age, gender, and baseline LV volumes, subjects with a baseline orexin A ≥ 1.04 ng/mL were less likely to have increase in LVEDVi (relative risk [RR] 0.51; 95% confidence interval [CI]: 0.30-0.84, P = 0.007) or LVESVi (RR 0.49; 95% CI: 0.28-0.85, P = 0.01). Follow up orexin concentrations did not add to baseline values for predicting LVRR. Conclusions: Orexin A is a unique prognostic biomarker for myocardial remodeling in chronic HFrEF.