亲环素 A 可预测行心肌内膜活检的充血性心力衰竭患者的临床转归。
Cyclophilin A predicts clinical outcome in patients with congestive heart failure undergoing endomyocardial biopsy.
机构信息
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Germany.
出版信息
Eur J Heart Fail. 2013 Feb;15(2):176-84. doi: 10.1093/eurjhf/hfs185. Epub 2012 Dec 12.
AIMS
Cyclophilin A (CyPA) represents a ubiquitous intracellular protein, which is secreted by inflammatory and by dying/necrotic cells. The aim of this study was to evaluate the prognostic relevance of CyPA expression in endomyocardial biopsies of consecutive patients with congestive heart failure.
METHODS AND RESULTS
A total of 227 unselected patients (age 53.9 ± 15 years) with congestive heart failure undergoing endomyocardial biopsy for diagnostic reasons were enrolled. Biopsies were analysed using established histopathological and immunohistological criteria together with CyPA staining. Virus genome was studied by polymerase chain reaction. CyPA was significantly enhanced in patients with inflammatory cardiomyopathy (n = 127) as compared with patients with non-inflammatory cardiomyopathy (n = 100, P < 0.0001). During a mean follow-up of 16.3 months, 60 patients (26.4%) reached the primary endpoint, a composite of all-cause death, heart transplantation, malignant arrhythmia, and heart failure-related rehospitalization. Of all clinical (ejection fraction, New York Heart Association functional class), laboratory (brain natriuretic peptide), and immunohistological parameters (CyPA, extracellular matrix metalloproteinase inducer, CD68, CD3, major hisocompatibility complex II, and virus genome) tested, only CyPA was identified as an independent predictor for the composite endpoint [hazard ratio (HR) 2.4; 95% confidence interval (CI) 1.2-5.2; P = 0.019] as well as for all-cause death and heart transplantation alone (HR 4.7; 95% CI 1.1-19.8; P = 0.036). Subgroup analysis revealed CyPA as a predictor in patients with non-inflammatory cardiomyopathy for the composite endpoint (HR 3.0; 95% CI 1.3-6.6; P = 0.007) as well as all-cause death or heart transplantation alone (HR 6.4; 95% CI 1.4-28.1; P = 0.014).
CONCLUSIONS
CyPA is an independent predictor of clinical outcome in patients with congestive heart failure undergoing endomyocardial biopsy.
目的
亲环素 A（CyPA）是一种普遍存在于细胞内的蛋白质，可由炎症细胞和死亡/坏死细胞分泌。本研究旨在评估连续心力衰竭患者心内膜心肌活检中 CyPA 表达的预后相关性。
方法和结果
共纳入 227 例因诊断原因接受心内膜心肌活检的心力衰竭患者（年龄 53.9±15 岁）。使用既定的组织病理学和免疫组织化学标准以及 CyPA 染色分析活检。通过聚合酶链反应研究病毒基因组。与非炎症性心肌病患者（n=100）相比，炎症性心肌病患者（n=127）的 CyPA 明显增强（P<0.0001）。在平均 16.3 个月的随访期间，60 例患者（26.4%）达到了主要终点，即全因死亡、心脏移植、恶性心律失常和心力衰竭相关再住院的复合终点。在所有临床（射血分数、纽约心脏协会功能分级）、实验室（脑钠肽）和免疫组织化学参数（CyPA、细胞外基质金属蛋白酶诱导剂、CD68、CD3、主要组织相容性复合物 II 和病毒基因组）中，只有 CyPA 被确定为复合终点的独立预测因子[危险比（HR）2.4；95%置信区间（CI）1.2-5.2；P=0.019]，以及全因死亡和单独心脏移植的独立预测因子（HR 4.7；95%CI 1.1-19.8；P=0.036）。亚组分析显示，CyPA 是非炎症性心肌病患者复合终点（HR 3.0；95%CI 1.3-6.6；P=0.007）和全因死亡或单独心脏移植（HR 6.4；95%CI 1.4-28.1；P=0.014）的预测因子。
结论
CyPA 是接受心内膜心肌活检的心力衰竭患者临床结局的独立预测因子。
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