title: Serum Matrix Metalloproteinases as Quantitative Biomarkers for Myocardial Fibrosis and Sudden Cardiac Death Risk Stratification in Patients With Hypertrophic Cardiomyopathy.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; German Centre for Cardiovascular Research, Hamburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Münch
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maxim
authors.initials: M
authors.lastname: Avanesov
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bannas
authors.affiliation: Institute of Computational Neuroscience, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Säring
authors.affiliation: German Centre for Cardiovascular Research, Hamburg, Germany; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Krämer
authors.affiliation: German Centre for Cardiovascular Research, Hamburg, Germany; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Giulia
authors.initials: G
authors.lastname: Mearini
authors.affiliation: German Centre for Cardiovascular Research, Hamburg, Germany; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrier
authors.affiliation: Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Suling
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Lund
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany; German Centre for Cardiovascular Research, Hamburg, Germany. Electronic address: patten@uke.de.
authors.forename: Monica
authors.initials: M
authors.lastname: Patten
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality* / Q000503:physiopathology; D015331:Cohort Studies; D016001:Confidence Intervals; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D016017:Odds Ratio; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D020782:Matrix Metalloproteinases
keywords: Collagen turnover; cardiac magnetic resonance imaging; syncope; ventricular tachycardia