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

• We examined the effect of carvedilol for CHF patients based on β1-AAb positivity.
• Reverse remodeling during carvedilol therapy was correlated with β1-AAb titer.
• β1-AAb titer was an independent predictor of reverse remodeling.
• In DCM, the lowest dose group had worse outcome only in the β1-AAb–negative group.

BackgroundAutoantibody against β1-adrenergic receptors (β1-AAb) exerts agonist-like action inducing receptor uncoupling and myocardial damage. We attempted to determine the significance of β1-AAb in chronic heart failure (CHF) patients who received carvedilol in a substudy of the Japanese Chronic Heart Failure study.Methods and ResultsIn this prospective, randomized, multicenter trial, 117 patients were assigned to 2.5 mg, 5 mg, and 20 mg (n = 38, 36, and 43) carvedilol groups according to the target dose. β1-AAb was positive in 51 patients (44%, P) and negative in 66 (56%, N). The percentage increase of left ventricular ejection fraction over 56 weeks (ΔLVEF) was larger in P than in N (P = .050) and in the high-titer group (H) than in the low-titer group (L; P = .04). Left ventricular (LV) volume decreased to a greater extent in H than in L over 56 weeks. β1-AAb titer was significantly correlated with ΔLVEF and the percentage change of LV volume and was an independent predictor of them. No difference was seen in the composite end point (all-cause mortality and hospitalization for cardiovascular diseases or heart failure). However, in patients with dilated cardiomyopathy, it was more common in the 2.5 mg group than in the other groups in N, and it was similar among the 3 groups in P.ConclusionsOur data suggest that the presence of β1-AAb is associated with favorable response to carvedilol in CHF.