Zuern Christine S, Walker Britta, Sauter Martina, Schaub Malte, Chatterjee Madhumita, Mueller Karin, Rath Dominik, Vogel Sebastian, Tegtmeyer Roland, Seizer Peter, Geisler Tobias, Kandolf Reinhard, Lang Florian, Klingel Karin, Gawaz Meinrad, Borst Oliver
Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076, Tuebingen, Germany.
Clin Res Cardiol. 2015 Dec;104(12):1033-43. doi: 10.1007/s00392-015-0871-y. Epub 2015 May 26.
Risk stratification in patients with suspected myocarditis is pivotal for optimizing therapy. Stromal cell-derived factor 1 (SDF-1) is an inflammatory chemokine expressed in the inflamed and failing myocardium. Therefore, we aimed to investigate whether endomyocardial expression of SDF-1 identifies high-risk patients with suspected myocarditis.
We prospectively enrolled 174 patients with non-ischemic HF who underwent endomyocardial biopsy for suspected myocarditis. Biopsies were analyzed using established histopathological and immunohistological criteria together with SDF-1 staining. SDF-1 was significantly enhanced in patients with inflammatory cardiomyopathy (65.4 % positive biopsies) as compared to patients with non-inflammatory cardiomyopathy (19.1 %, p < 0.001). SDF-1 expression levels correlated significantly with the degree of myocardial fibrosis (correlation coefficient r = 0.196; p = 0.010) since patients with severe myocardial fibrosis displayed high myocardial SDF-1 expression. During a mean follow-up of 27.5 months, 20 patients (11.5 %) died. The 4-year mortality rate was 26.0 % among the 92 SDF-1-positive patients vs. 9.5 % among the 82 SDF-1-negative patients (p = 0.001). On multivariable analysis which considered clinical (NYHA functional class, left ventricular ejection fraction), laboratory (brain natriuretic peptide, troponin I) and biopsy staining, SDF-1 was the strongest independent predictor of mortality (hazard ratio 6.1; 95 % confidence interval 1.4-27.5; p = 0.018). Subgroup analysis revealed SDF-1 as a predictor of mortality in both patients with inflammatory and non-inflammatory cardiomyopathy.
Endomyocardial expression of SDF-1 is enhanced in inflammatory cardiomyopathy, positively correlates with myocardial fibrosis and identifies high-risk patients with suspected myocarditis.
疑似心肌炎患者的风险分层对于优化治疗至关重要。基质细胞衍生因子1（SDF-1）是一种在炎症和衰竭心肌中表达的炎性趋化因子。因此，我们旨在研究SDF-1的心内膜表达是否能识别疑似心肌炎的高危患者。
我们前瞻性纳入了174例因疑似心肌炎接受心内膜心肌活检的非缺血性心力衰竭患者。活检组织采用既定的组织病理学和免疫组织学标准以及SDF-1染色进行分析。与非炎性心肌病患者（19.1%，p<0.001）相比，炎性心肌病患者的SDF-1显著增强（活检阳性率65.4%）。SDF-1表达水平与心肌纤维化程度显著相关（相关系数r=0.196；p=0.010），因为严重心肌纤维化患者的心肌SDF-1表达较高。在平均27.5个月的随访期间，20例患者（11.5%）死亡。92例SDF-1阳性患者的4年死亡率为26.0%，而82例SDF-1阴性患者的4年死亡率为9.5%（p=0.001）。在考虑临床（纽约心脏协会功能分级、左心室射血分数）、实验室（脑钠肽、肌钙蛋白I）和活检染色的多变量分析中，SDF-1是死亡率最强的独立预测因子（风险比6.1；95%置信区间1.4-27.5；p=0.018）。亚组分析显示，SDF-1是炎性和非炎性心肌病患者死亡率的预测因子。
炎性心肌病患者的心内膜SDF-1表达增强，与心肌纤维化呈正相关，并可识别疑似心肌炎的高危患者。
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