Clinical significance of different assesment methods of myocardial fibrosis in patients with hypertrophic cardiomyopathy.

Abstract

Objective To evaluate prospects for clinical use of circulating biomarkers for characterizing fibrotic changes in the myocardium of patients with hypertrophic cardiomyopathy (HCMP) with left ventricular (LV) outflow tract obstruction.Materials and Methods This was a prospective study with a 12-month follow-up period. The study included 47 patients (29 females and 18 males) with obstructive HCMP who were selected for septal reduction. Echocardiography (EchoCG), cardiac magnetic resonance imaging (MRI) and measurements of serum C-reactive protein, N-terminal pro-brain natriuretic peptide, and relevant circulating markers of fibrosis (TGF-β1, MMP-2,-9, TIMP-1, galectin-3, sST2, CITP, PICP, and PIIINP) were performed for all patients. All patients were evaluated at baseline and at 7 days, 6 and 12 months following surgical treatment. Morphometrical analysis of intraoperative biopsy samples was performed for evaluation of the degree of fibrotic changes. Patients received beta-blockers (95.7%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (34%), loop diuretics (68.1%), aldosterone antagonists (34%), and statins (66%).Results Women with HCMP were older and more frequently had additional risk factors (arterial hypertension). Men had a higher risk of sudden cardiac death. Histological study of intraoperative myocardial biopsy samples showed that the area of fibrotic changes was 13.9±6.9%. According to cardiac MRI mean area of delayed contrast enhancement was 8.7±3.3% of LV myocardial mass. No association was established between traditional cardiovascular risk factors and severity of myocardial fibrotic changes or levels of circulating fibrosis markers. Perhaps that was due to the modifying effect of the drug therapy received by HCMP patients. According to EchoCG maximum pressure gradient in the LV outflow tract before the surgical treatment was 88 (55; 192) mm Hg, and interventricular septal thickness was 22 (16; 32) mm. A considerable decrease (p=0.0002) in the LV outflow tract gradient was observed after myectomy in all patients. At the same time, the left ventricular dimension, which tended to decrease in the early postoperative period, returned to baseline values by the 6th month of follow-up.Conclusion The study confirmed the increase in relevant circulating markers of fibrosis in patients with obstructive HCMP. At the same time, no correlation was observed between levels of circulating biomarkers and severity of fibrosis according to data of histology and cardiac MRI, which was probably due to the modifying effect of drug therapy and limited sampling.

Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy

“…On the one hand, there have been studies on DCM, HCM, and patients with CAD that showed correlations between galectin-3 and MMP-9 with LGE [ 30 , 31 , 32 ]. Conversely, studies on HCM, which explored TGF-β1; MMP-2 and MMP-9; TIMP-1; galectin-3; sST2; CITP, PICP, and PIIINP; hypertensive HF with PICP, PIIINP, CITP and MMP-1; valvular diseases (MMP-2, TIMP-1); and acute myocardial infraction populations (sST2) have reported a lack of any relationship between the biomarkers under analysis and LGE [ 33 , 34 , 35 , 36 ].…”

Molecular biomarker profile of heart failure with mid-range and preserved ejection fraction in patients with type 2 diabetes

“…В литературе на текущий момент представлены немногочисленные исследования, посвященные изучению данного маркера обмена экстрацеллюлярного матрикса при СНпФВ в основном в рамках метаанализов рандомизированных клинических исследований [25]. Учитывая неоднозначные данные о диагностической значимости PICP в зависимости от этиологии СН, сопутствующих заболеваний, влияющих на метаболизм коллагена, выявленные различия в концентрациях описываемого биомаркера по результатам нашего исследования требуют дальнейшего изучения [26,27].…”

Prognostic value of morphological, biochemical, molecular markers of fibrosis in patients with hypertrophic cardiomyopathy

“…У всех участников было подтверждено повышение уровней MMP-2, -9, ТИМП-1, Gal-3, sST2, CITP, PICP, PIIINP, транс формирующего фактора роста-β1. Однако корреляции между уровнем биомаркеров и степенью фиброза по данным морфометрического анализа интраоперационных биоптатов миокарда и МРТ сердца не выявлено [49]. В 2020г Vullaganti S, et al стремились связать наличие замещающего фиброза, измеряемого методом ПНГ, и диффузного фиброза, измеряемого по внеклеточному объему коллагена с помощью МРТ, с выявленными ВНП в генах саркомерных белков.…”