Evaluation of circulating biomarkers and expression of relevant fibrosis genes in patients with obstructive hypertrophic cardiomyopathy

Aim. To compare the profile of circulating biomarkers and expression of relevant fibrosis genes in the myocardium with clinical and morphological data on the severity of myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy (HCM) who underwent septal myectomy.

Materials and methods. This prospective study included 69 patients with obstructive HCM and indications for septal reduction. The results of paraclinical investigation, echocardiography, cardiac magnetic resonance imaging, histological examination, serum biomarker levels (transforming growth factor beta-1 (TGF-β1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), galectin-3, soluble interleukin-1 receptor 4 (ST2) (sST2), C-telopeptide of type I collagen (CITP), C-terminal propeptide of type I collagen (PICP) and N-terminal propeptide of type III procollagen (PIIINP)), analysis of RNA obtained from intraoperative myocardial biopsies were assessed.

Results. Increased serum levels of galectin-3, TGF-β1, sST2 and collagen synthesis markers, as well as the level of the collagen degradation marker CITP were revealed. Relationships were established between the PIIINP level and interventricular septum thickness indexed to the body surface area (p=0,049), as well as the left atrial diameter (p=0,024). An increase in the expression levels of relevant fibrosis genes, with the exception of TIMP1, was noted. An increased level of circulating PIСP was associated with an increase in the expression of galectin-3 and interleukin-1 receptor type 1 genes in the myocardium. Septal myectomy allowed revealing that patients without improvement in N-terminal pro-brain natriuretic peptide had a higher sST2 level. A negative relationship was established between the MMP9 gene expression in the myocardium and changes of the left atrial size in the long-term period after septal myectomy (p=0,032).

Conclusion. The profile of circulating biomarkers is associated with the expression of relevant fibrosis genes in the myocardium and is a promising non-invasive method for assessing the activity of fibrosis processes. Myocardial fibrosis plays an important role in assessing the prognosis during the follow-up of patients with HCM.

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