Münch Julia, Avanesov Maxim, Bannas Peter, Säring Dennis, Krämer Elisabeth, Mearini Giulia, Carrier Lucie, Suling Anna, Lund Gunnar, Patten Monica
Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; German Centre for Cardiovascular Research, Hamburg, Germany.
Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Card Fail. 2016 Oct;22(10):845-50. doi: 10.1016/j.cardfail.2016.03.010. Epub 2016 Mar 24.
Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia (VT), and myocardial fibrosis reflects an important risk factor. Several matrix metalloproteinases (MMPs) and procollagen N-terminal propeptides (PNPs) are involved in collagen turnover and discussed as fibrosis biomarkers. We aimed to identify biomarkers that correlate with myocardial fibrosis in late-gadolinium-enhancement cardiac magnetic resonance imaging (LGE-CMR) and/or cardiac events (syncope, VT) in HCM patients.
In 54 HCM patients (age 55.9 ± 14.3 y, 50% female) fibrosis was quantified by LGE-CMR. Serum concentrations of MMP-1, -2, -3, -9, and tissue inhibitor of MMP (TIMP) 1 were analyzed by means of enzyme-linked immunosorbent assay and PINP, PIIINP, and type I collagen C-terminal telopeptide (ICTP) concentrations by radioimmunoassay. MMP-9 was associated with fibrosis in LGE-CMR (mean increase 0.66 g/unit MMP9 [95% confidence interval [CI] 0.50-0.82]; P < .001) and with cardiac events in women (odds ratio [OR] 1.07 [1.01-1.12], P = .01) but not in men. Increased MMP-2 levels in women were associated with lower fibrosis (0.05 [-0.09 to -0.01]; P = .015). MMP-3 levels were positively associated with cardiac events (OR 1.13 [1.05-1.22]; P = .001) independently from fibrosis and sex. No association was detected for MMP-1, TIMP-1, PNPs, and ICTP.
These data suggest that MMP-9 is a useful biomarker for fibrosis and cardiac events in female HCM patients, whereas MMP-3 is associated with a higher event rate independent from fibrosis and sex.
肥厚型心肌病（HCM）与室性心动过速（VT）导致的心源性猝死风险增加相关，心肌纤维化是一个重要的危险因素。几种基质金属蛋白酶（MMPs）和前胶原N端前肽（PNPs）参与胶原蛋白周转，被视为纤维化生物标志物。我们旨在识别与HCM患者延迟钆增强心脏磁共振成像（LGE-CMR）中的心肌纤维化和/或心脏事件（晕厥、VT）相关的生物标志物。
对54例HCM患者（年龄55.9±14.3岁，50%为女性）进行LGE-CMR以量化纤维化。采用酶联免疫吸附测定法分析血清MMP-1、-2、-3、-9和基质金属蛋白酶组织抑制剂（TIMP）1的浓度，采用放射免疫测定法分析PINP、PIIINP和I型胶原C端肽（ICTP）的浓度。MMP-9与LGE-CMR中的纤维化相关（平均增加0.66 g/单位MMP9 [95%置信区间[CI] 0.50 - 0.82]；P < 0.001），且与女性的心脏事件相关（比值比[OR] 1.07 [1.01 - 1.12]，P = 0.01），但与男性无关。女性MMP-2水平升高与较低的纤维化相关（0.05 [-0.09至-0.01]；P = 0.015）。MMP-3水平与心脏事件呈正相关（OR 1.13 [1.05 - 1.22]；P = 0.001），与纤维化和性别无关。未检测到MMP-1、TIMP-1、PNPs和ICTP之间的关联。
这些数据表明，MMP-9是女性HCM患者纤维化和心脏事件的有用生物标志物，而MMP-3与较高的事件发生率相关，与纤维化和性别无关。
