Department of Pathology, University Hospital Favaloro Foundation, Buenos Aires, Argentina.
J Am Coll Cardiol. 2011 Apr 5;57(14):1523-31. doi: 10.1016/j.jacc.2010.09.080.
The aim of this study was to identify the remodeling parameters cardiomyocyte (CM) damage or death, hypertrophy, and fibrosis that may be linked to outcomes in patients with advanced heart failure (HF) in an effort to understand the pathogenic mechanisms of HF that may support newer therapeutic modalities.
There are controversial results on the influence of fibrosis, CM hypertrophy, and apoptosis on outcomes in patients with HF; other modalities of cell damage have been poorly investigated.
In endomyocardial biopsy specimens from 100 patients with idiopathic dilated cardiomyopathy and advanced HF, CM diameter and the extent of fibrosis were determined by morphometry. The proportion of CMs with evidence of apoptosis, autophagic vacuolization (AuV), and oncosis was investigated by immunohistochemical methods and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. Those parameters were correlated with mortality in 3 years of follow-up by univariate analysis and with multivariate models incorporating the clinical variables more relevant to the prediction of outcomes.
CM AuV occurred in 28 patients (0.013 ± 0.012%) and oncosis in 41 (0.109 ± 0.139%). Nineteen patients showed both markers. Apoptotic CM nuclei were observed in 3 patients. In univariate analysis, CM diameter and AuV, either alone or associated with oncosis, were predictors of mortality. In multivariate analysis, CM diameter (hazard ratio: 1.37; 95% confidence interval: 1.12 to 1.68; p = 0.002) and simultaneous presence in the same endomyocardial biopsy specimen of AuV and oncosis (hazard ratio: 2.82; 95% confidence interval: 1.12 to 7.13; p = 0.028) were independent predictors of mortality.
CM hypertrophy and AuV, especially in association with oncosis, are predictors of outcome in patients with idiopathic dilated cardiomyopathy and severe HF.
本研究旨在识别与晚期心力衰竭（HF）患者结局相关的心肌细胞（CM）损伤或死亡、肥大和纤维化的重塑参数，以了解可能支持新型治疗方法的 HF 发病机制。
纤维化、CM 肥大和细胞凋亡对 HF 患者结局的影响存在争议；其他细胞损伤方式研究甚少。
在 100 例特发性扩张型心肌病和晚期 HF 患者的心肌活检标本中，通过形态计量学确定 CM 直径和纤维化程度。通过免疫组织化学方法和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法研究凋亡、自噬空泡（AuV）和胀亡的 CM 比例。通过单变量分析和纳入与结局预测更相关的临床变量的多变量模型，将这些参数与 3 年随访期间的死亡率相关联。
28 例（0.013±0.012%）患者存在 CM AuV，41 例（0.109±0.139%）患者存在胀亡。19 例患者同时存在这两种标志物。3 例患者存在凋亡的 CM 核。单变量分析显示，CM 直径和 AuV 单独或与胀亡相关，是死亡率的预测因素。多变量分析显示，CM 直径（危险比：1.37；95%置信区间：1.12 至 1.68；p=0.002）和同一心肌活检标本中同时存在 AuV 和胀亡（危险比：2.82；95%置信区间：1.12 至 7.13；p=0.028）是死亡率的独立预测因素。
CM 肥大和 AuV，尤其是与胀亡同时存在，是特发性扩张型心肌病和严重 HF 患者结局的预测因素。
