Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
Department of Cardiology, Sakakibara Heart Institute, Fuchu, Japan.
J Card Fail. 2015 Mar;21(3):198-207. doi: 10.1016/j.cardfail.2014.12.005. Epub 2014 Dec 18.
Autoantibody 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.
In 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.
Our data suggest that the presence of β1-AAb is associated with favorable response to carvedilol in CHF.
β1-肾上腺素能受体自身抗体(β1-AAb)发挥激动剂样作用,导致受体解偶联和心肌损伤。我们试图在日本慢性心力衰竭研究的亚研究中确定接受卡维地洛的慢性心力衰竭(CHF)患者中β1-AAb 的意义。
在这项前瞻性、随机、多中心试验中,根据目标剂量,117 名患者被分配到 2.5 mg、5 mg 和 20 mg(n=38、36 和 43)卡维地洛组。51 名患者(44%,P)β1-AAb 阳性,66 名(56%,N)阴性。56 周时左心室射血分数的百分比增加(ΔLVEF)在 P 组大于 N 组(P=0.050),在高滴度组(H)大于低滴度组(L;P=0.04)。56 周时,H 组的左心室(LV)容积较 L 组下降更为明显。β1-AAb 滴度与ΔLVEF 和 LV 容积变化百分比显著相关,是其独立预测因子。复合终点(全因死亡率和心血管疾病或心力衰竭住院)无差异。然而,在扩张型心肌病患者中,在 N 中,2.5 mg 组比其他组更常见,而在 P 中,3 组之间相似。
我们的数据表明,β1-AAb 的存在与 CHF 患者对卡维地洛的良好反应相关。