Abstract 11884: Presence of Autoantibody Directed against β1-Adrenergic Receptors is Associated with Amelioration of Cardiac Function in Response to Carvedilol: Japanese Chronic Heart Failure (J-CHF) Study
Background: Autoimmune disorder is one of the features characterizing congestive heart failure (CHF) not only due to idiopathic dilated cardiomyopathy (DCM), but due to other etiologies. Autoantibody against β1-adrenergic receptors (β1AAB) exerts agonist-like action inducing receptor uncoupling, and elicits persistent myocardial damage in such patients. We, therefore, attempted to determine the significance of β1AAB in CHF patients who received β-blocker carvedilol in the substudy of J-CHF study.
Methods and materials: In this prospective, randomized, multicenter, stratified trial, 364 CHF patients (EF ≤ 40%) were assigned to carvedilol 2.5 mg, 5 mg, or 20 mg daily, plus optimal standard therapy. One-hundred eighteen patients (age 60±14 years old, Male 88) were available for the intention-to-treat analyses in the substudy. Study subjects were randomly assigned to 2.5 mg (n=39), 5 mg (n=36), and 20 mg (n=43) group according to the target dose. Sera were collected and presence of β1AAB was determined using ELISA.
Results: β1AAB was found to be positive in 51 patients (P, 43%), and negative in the remaining 67 (N). There was no difference in dose assignment (2.5 mg/5mg/20mg; P, 15/21/15; N, 24/15/28), final fixed dose (8.8±7.6 mg vs. 10.0±7.9 mg, NS), or cardiac function at baseline between P and N. Left ventricular ejection fraction (LVEF) measured by ultrasonic echocardiography tended to be larger in P than N 48 weeks after introduction of carvedilol (49±13% vs. 41±14%, p=0.05). Left ventricular end-diastolic dimension tended to be smaller in P than N (5.4±1.0 cm vs. 5.8±0.8 cm, p=0.09). Left ventricular end-systolic dimension was significantly smaller in P than N (4.2±1.1 cm vs.4.5±1.0 cm, p=0.01). During 38±18 months follow-up, no significant difference was seen in the composite primary endpoint of all-cause mortality and hospitalization for cardiovascular diseases and heart failure (25% in P and 22% in N, p=0.85). However, in DCM patients, primary endpoint was significantly higher in 2.5 mg group than other groups in N (p=0.03). There was no difference in the primary endpoint according to the 3 groups in P.
Conclusions: Our study data suggest that the presence of β1AAB is associated with favorable response to carvedilol in CHF patients.
- © 2012 by American Heart Association, Inc.