Serum Matrix Metalloproteinases as Quantitative Biomarkers for Myocardial Fibrosis and Sudden Cardiac Death Risk Stratification in Patients With Hypertrophic Cardiomyopathy

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• 作者：Julia Mü ; nch ; MD¹ ; ² ; Maxim Avanesov ; MD³ ; Peter Bannas ; MD³ ; Dennis Sä ; ring ; PhD⁴ ; Elisabeth Krä ; mer² ; ⁵ ; Giulia Mearini ; PhD² ; ⁵ ; Lucie Carrier ; PhD² ; ⁵ ; Anna Suling ; PhD⁶ ; Gunnar Lund ; MD³ ; Monica Patten ; MD¹ ; ² ; ^{patten@uke.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Collagen turnover ; syncope ; ventricular tachycardia ; cardiac magnetic resonance imaging
• 刊名：Journal of Cardiac Failure
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：22
• 期：10
• 页码：845-850
• 全文大小：295 K

文摘

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.

Methods and Results

15">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.

Conclusions

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.