Myocardial fibrosis (MF) is considered a result of microvascular dysfunction in patients with hypertrophic cardiomyopathy (HCM). Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), capable to degrade collagen, directly participate in the development of MF. First, we investigated the relationships among MF, microvascular rarefaction and MMPs. Then, we assessed the prognostic value of MF-related circulating biomarkers.
55 obstructive hypertrophic cardiomyopathy (HOCM) patients were enrolled following surgical myectomy.Myocardial samples were performed with Masson’s trichrome staining and immunohistochemical procedures to collagen volume fraction (CVF) and microvascular density (MVD) respectively. Enzyme-linked immunosorbent assays (ELISA) were used to assess myocardial and plasma of MMP-2, MMP-9 and TIMP-1,and plasma C-terminal propeptide of procollagen type Ⅰ (PICP) and C-terminal telopeptide of type Ⅰ collagen (ICTP) levels. The composite cardiovascular(CV) endpoint consisted of new onset atrial fibrillation, heart failure requiring hospitalization and all-cause death.
In HOCM patients, MVD was associated with the myocardail MMP-2:TIMP-1 ratio (r=-0.348, P=0.009), whereas no correlation was found between CVF and myocardial MMPs. During the 44-month follow-up, 6 patients were experienced a CV endpoint. The plasma PICP:ICTP ratio and MMP-2:TIMP-1 ratio were the two strongest prognostic makers. In multivariable analyses, high PICP:ICTP and MMP-2:TIMP-1 ratios remained independent predictors of CV outcomes after adjustment for clinical confounders (HR=12.683, P=0.021; HR=17.037, P=0.027).
In HOCM patients, the myocardial MMP-2:TIMP-1 ratio is elevated due to microvascular rarefaction but may not be responsible for MF. High plasma PICP: ICTP and MMP-2:TIMP-1 ratios are independent predictors of adverse outcomes in HOCM patients.
Copyright © 2020. Published by Elsevier Inc.