Abstract 11087: Autoantibody Titer Directed Against β1-Adrenergic Receptors is a Predictor of Reverse Remodeling During Carvedilol Therapy for Chronic Heart Failure: Japanese Chronic Heart Failure (J-CHF) Study

Abstract

Introduction: Autoimmune disorder is one of the features characterizing congestive heart failure (CHF) not only due to idiopathic dilated cardiomyopathy, but due to other etiologies. Autoantibody directed against β1-adrenergic receptors (β1-AAb) exerts agonist-like action inducing receptor uncoupling, and elicits persistent myocardial damage. We, therefore, attempted to determine the significance of β1-AAb in patients with CHF who received β-blocker carvedilol in the substudy of J-CHF study. Methods: In this prospective, randomized, multicenter trial, 117 patients (left ventricular ejection fraction [LVEF] ≤ 40%) with mild to moderate CHF were assigned to 2.5mg/5mg/20mg (n=38/36/43) carvedilol groups according to the target dose. Sera were collected at baseline and β1-AAb titer was determined using ELISA. Results: ELISA showed 66 patients as negative and 36/7/7/1 patients as 20-fold (x20) / x40 / x80 / x160 positive, respectively. When the study population was divided into β1-AAb high titer (≥ x40, H) and low titer (≤ x20, L) groups, there were no significant differences in vital signs or cardiac function at baseline between 2 groups. The % change of LVEF during 56 weeks after carvedilol introduction (ΔLVEF) was significantly larger in H than L (H, +85±78% vs. L, +43±65%, p=0.04). LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) decreased to a greater extent in H than L during 56 weeks (LVEDV, 182±50 to 119±43 ml vs. 202±52 to 167±58 ml, p<0.005 by ANOVA; LVESV, 136±47 to 62±36 ml vs. 141±47 to 97±53 ml, p=0.048 by ANOVA). β1-AAb titer was significantly correlated with ΔLVEF and the % change of LV volume (LVEF, r=0.24, p=0.02; LVEDV, r=-0.26, p=0.02; LVESV r=-0.27, p=0.01). Multiple regression analysis demonstrated that β1-AAb titer was an independent predictor of ΔLVEF and the % changes of LV volume after adjusting for age, gender, allocated dose of carvedilol, heart rate at baseline, plasma BNP at baseline, etiology of CHF and the presence of atrial fibrillation (ΔLVEF β=0.286, p=0.01; ΔLVEDV β=-0.227, p=0.04; ΔLVESV, β=-0.250, p=0.02). Conclusions: The findings in the present study suggested that β1-AAb has a crucial role as one of the determinants of reverse remodeling during carvedilol therapy for patients with CHF.