Nagatomo Yuji, McNamara Dennis M, Alexis Jeffrey D, Cooper Leslie T, Dec G William, Pauly Daniel F, Sheppard Richard, Starling Randall C, Tang W H Wilson
Heart and Vascular Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Sakakibara Heart Institute, Fuchu, Japan.
Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
J Am Coll Cardiol. 2017 Feb 28;69(8):968-977. doi: 10.1016/j.jacc.2016.11.067.
Among various cardiac autoantibodies (AAbs), those recognizing the β-adrenergic receptor (βAR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption.
The goal of this study was to investigate the role of βAR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy.
Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-βAR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months.
Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-βAR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-βAR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint.
IgG3-βAR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.
在各种心脏自身抗体（AAbs）中，那些识别β-肾上腺素能受体（βAR）的抗体表现出激动剂样作用，并可导致心肌损伤，而β受体阻滞剂和免疫球蛋白G3（IgG3）免疫吸附可逆转这种损伤。
本研究旨在探讨IgG3亚类的βAR-AAbs在近期发病的心肌病患者中的作用。
对近期发病的心肌病患者（左心室射血分数[LVEF]≤0.40；病程<6个月）在入组时采集外周血样本。测定IgG和IgG3-βAR-AAb的存在情况，并在基线和6个月时评估超声心动图。对患者进行≤48个月的随访。
在353例有足够血液样本用于分析的患者中，62例（18%）IgG3-βAR-AAbs呈阳性（IgG3组），58例（16%）IgG呈阳性但IgG3呈阴性（非IgG3组），其余为阴性。各组在基线时的收缩压、心率或LVEF无显著差异。与其他组相比，非IgG3组的左心室舒张末期和收缩末期直径显著更大（左心室舒张末期直径，p<0.01；左心室收缩末期直径，p=0.03）。在6个月时，IgG3组的LVEF显著更高（p=0.007）。多元回归分析显示，即使在多变量调整后，IgG3-βAR-AAb仍是6个月时LVEF及6个月内LVEF变化的独立预测因子（6个月时的LVEF，β=0.20，p=0.01；LVEF变化，β=0.20，p=0.008）。在基线时纽约心脏协会功能分级较高（III或IV级）的患者中，IgG3组全因死亡、心脏移植和因心力衰竭住院的复合终点发生率较低，而非IgG3组的复合终点发生率最高。
IgG3-βAR-AAbs与近期发病的心肌病患者更良好的心肌恢复相关。
