The objective of our study was to evaluate the concentrations of pro-inflammatory biomarkers in patients with acute myocardial infarction with non-obstructive coronary arteries (MINOCA) compared to patients with acute myocardial infarction with obstructive coronary arteries (MI-CAD) in the early post-infarction period and after 1 year and to perform a comparative analysis of the relationship between laboratory biomarkers and atherosclerosis progression in patients with MINOCA and MI-CAD. Methods: Samples of peripheral venous blood were collected upon admission and on days 2, 4, and 7 of hospitalization and after 1 year. An extended multiplex analysis was performed in blood serum. Multidetector-computed tomography coronary angiography was performed on day 7 and 1 year after acute myocardial infarction to assess the progression of atherosclerosis. Results: The level of high-sensitive C-reactive protein (hsCRP) was elevated upon admission in MINOCA patients compared to MI-CAD patients (p = 0.05), but it was comparable in two groups at other time points and did not exceed the reference range after 1 year. Despite comparable levels of cytokines CXCL-6, LIGHT, CCL-8, and endocan-1 in patients in both groups, MINOCA patients had a greater increase in pro-inflammatory cytokines PlGF, oncostatin M, IL-20, and CCL-15 sVCAM-1 in the early post-infarction period and in CCL-21, sVCAM-1, oncostatin M, and PlGF after 1 year. We observed significant differences in the dynamics of the following biomarkers between patients with MI-CAD and MINOCA: the dynamics of concentrations of CCL21 (p = 0.002), LIGHT (p = 0.03), and endocan-1 (p = 0.03) after 1 year compared to day 1 in MI-CAD and MINOCA patients was opposite, while the dynamics of CXCL6 (p = 0.04) and endocan-1 (p = 0.02) differed between groups when evaluated after 1 year compared to day 7 of the early post-infarction period. In the MINOCA group, factors associated with atherosclerosis progression were concentrations of sVCAM-1 and CCL-21, while in the MI-CAD group, concentrations of CCL-8 and CXCL6 were the main determinants of atherosclerosis progression. Conclusions: This small study showed that MINOCA and MI-CAD patients exhibited differences in a pro-inflammatory biomarker profile in the early post-infarction period and after 1-year follow-up, which implies distinct inflammatory pathways involved in atherogenesis during MINOCA. The key factors that were associated with atherosclerosis progression in MINOCA patients are sVCAM-1 and CCL-21, which may suggest a complex genesis of atherosclerosis progression due to structurally altered plaques and changes in the microcirculatory bed. In MI-CAD patients, CCL-8 and CXCL-6 were the key biomarkers associated with atherosclerosis progression. Further large-scale studies are required to confirm our data.

The relationship between prothrombotic activity and coronary microvascular dysfunction (MVD) is limited. This study aimed to perform a comparative analysis of the relationship between prothrombotic activity and MVD in patients with myocardial infarction without obstructive coronary artery disease (MINOCA) and myocardial infarction with obstructive coronary artery disease (MI-CAD). Material and methods: A total of 37 patients were enrolled in the study; the main group included 16 MINOCA patients, and 21 MI-CAD patients were included in the control group. Blood samples for protein C, antithrombin, WF, plasminogen, and homocysteine were performed on the 4th ± 1 day of admission. CZT-SPECT data were used to determine the standard indices of myocardial perfusion dis-orders (SSS, SRS, and SDS), as well as stress and rest myocardial blood flow (MBF), myocardial flow reserve (MFR), and difference flows (DF). MVD was defined as MFR (≤ 1.91 ml/min); coronary slow flow (CSF) was defined as corrected TIMI frame count (21 ± 3). Results: We performed a step-by-step analysis of prothrombotic activity of the hemostasis system in binary logistic regression for MINOCA patients to identify factors associated with MVD (MFR ≤ 1.91 ml/min). A predictive model was developed to estimate the probability of reduced MFR. A low MFR is related to only plasminogen in MINOCA patients, whereas only wall motion score index (WMSI) in MI-CAD group was associated with a low MFR. Conclusion: This small-scale study revealed the relationship between indicators of prothrombotic activity and MVD. The key factors that affect MVD in MINOCA patients was plasminogen, whereas, in patients with MI-CAD, WMSI was the key factor. Measurements of MVD may enhance the risk stratification and facilitate future targeting of adjunctive antithrombotic therapies in MINOCA and MI-CAD patients.

Сравнительный анализ адренореактивности эритроцитов у пациентов с инфарктом миокарда в зависимости от выраженности коронарной обструкции

Aim.To compare parameters of prothrombotic activity in patients with myocardial infarction (MI) with obstructive (MICAD) and non-obstructive coronary artery disease (MINOCA).Material and methods.The study included 40 patients with MI, which were divided into experimental (n=19) and control group (n=21). Three patients (15,7%) with acute myocarditis were excluded from the analysis. Hemostasiological and hematological blood tests were studied upon admission, on the 2nd, 4th, 7th days from hospitalization. Blood samples for protein C, antithrombin, von Willebrand factor (VWF), plasminogen, homocysteine were performed on 4th±1 day from hospitalization. To determine the IgG/IgM anticardiolipin (aCL) and anti-beta 2 glycoprotein I (β2-GPI) antibodies in order to diagnose antiphospholipid syndrome (APS), the ORGENTEC Anti- β2-Glycoprotein I IgG/IgM ELISA enzyme immunoassay was used. Blood tests for lupus anticoagulant were performed using an ACL-Top 700 analyzer (Werfen) with HemosIL SynthASil dRVVT screen/dRVVT confirm and with a SCT screen/SCT confirm quartz activator.Results.According to the data obtained, it was found that patients with MINOCA had a significantly lower level of plasminogen (p=0,007), as well as a higher level of homocysteine (p=0,03). For such indicators as protein C, antithrombin, ejection fraction, differences between the groups were not revealed (p0,05). There was a higher platelet count in patients with MINOCA on the 2^ndand 4^thdays of acute MI (p=0,46 and p=0,01, respectively). However, the hemoglobin level in patients with MINOCA was significantly lower on admission, 4^thand 7^thday of MI (p=0,02, p=0,03 and p=0,04, respectively).Conclusion.According to the study results, in patients with MINOCA and MICAD, differences in blood thrombotic activity were revealed. A higher level of homocysteine and a lower level of plasminogen were determined in patients with MINOCA. For such parameters as protein C, antithrombin, VWF, aCL and β2-GPI antibodies, differences between the groups were not determined. According to laboratory data, patients with MINOCA showed higher platelet count, but lower levels of hemoglobin and hematocrit in the early postinfarction period.

Aim. To study the structural and functional status of coronary blood flow in patients with acute coronary syndrome with nonobstructive coronary arteries using multispiral computed tomography (MSCT) and single photon emission tomography (SPECT) and to compare data of MSCT and invasive coronary angiography (ICA).Material and Methods. This study is a non-randomized, open-label, controlled clinical trial. The study is registered on ClinicalTrials.gov. The inclusion criteria are listed on the site. All patients underwent CT and SPECT.Results. The study included 14 patients with MINOCA; the group comprised predominantly women (n=11, 78.6%); the average age was 61.1±14 years. The risk according to GRACE (Global Registry of Acute Coronary Events) risk score was moderate in 8 patients (57%) and high in 5 patients (35.7%). 85.7% of patients were admitted to hospital within the first six hours from onset of diseases. Three patients (21.4%) received thrombolytic therapy and it was effective in two of them (14%). Risk factors included hypertension (64.2%), dyslipidemia (50%), and burdened history (71.4). According to the results of invasive coronary angiography, intact coronary arteries were detected in 9 patients (64.3%); 5 patients (35.7%) had stenosis up to 50%. Coronary slow-flow phenomenon (TIMI 2) was detected in 11 patients (78.6%) including 8 patients (57.1%) who had coronary slow-flow phenomenon and intact coronary arteries. Severe coronary spasm was registered in 1 patient (7.1%) in the group with ST segment elevation acute coronary syndrome (STE ACS). According to MSCT data, the proportion of patients with intact coronary arteries decreased from 7 (50%) to 5 patients (35.7%) whereas the proportion of patients with nonstenosing atherosclerosis increased from 7 (50%) to 9 patients (64.3%). Twenty six atherosclerotic plaques were detected including eccentric (76%), circular (11.5%), and semi-circular plaques (11.5%). In regard to morphological structure, the atherosclerotic plaques were calcified (59.5%), mostly calcified (7.7%), and soft (29%). Normal myocardial perfusion (Summed Stress Score (SSS) and Summed Rest Score (SRS) <4) was detected in two patients (14.3%); 12 patients (85%) had transitory perfusion defects. The median score values were 7.5 (4; 13) for SSS, 4.7 (1.0; 9.0) for SRS, and 4.7 (3.0; 8.0) for SDS.Conclusion.The introduction of MCTA and SPECT into the algorithm of the examination of patients with acute myocardial infarction and non-obstructive atherosclerosis of the coronary arteries was safe when additionally used during index hospitalization. These approaches provided new information about the structure and function of the coronary arteries. These data provide rationale for further study using a larger group of patients to determine a prognostic significance of detecting the atherosclerotic plaques with the signs of instability in this patient category.

Aim. To study quantitative parameters of coronary atherosclerosis, according to computed tomography coronary angiography (CTCA), and to identify their association with the level of cardiac biomarkers in patients with acute myocardial infarction (MI).Material and methods. The study included patients with newly diagnosed MI. Depending on the coronary artery (CA) stenosis, two groups were formed: 1) MI with obstructive CA ≥50% (MICAD); 2) MI with non-obstructive CA <50% (MINOCA). All patients were assessed for cardiac biomarkers and underwent CTCA.Results. The study included 31 patients as follows: MINOCA group consisted of 10 patients (5 men aged 68 (57; 79) years); MICAD group — 21 patients (13 men aged 62 (56; 68) years). When analyzing cardiac biomarker levels, a significant increase in cardiac troponin I (cTnI) levels was noted on the 4^th (p=0,04) and on the 7^th day (p=0,0009) in MICAD patients. A significant predominance of the volume (p=0,01) and burden (p=0,004) of low-density plaques was revealed in the MICAD group compared to MINOCA. In addition, MICAD patients had significantly increased values of the total atherosclerotic burden (p=0,01) and the total burden of the soft tissue component of plaques (p=0,04). A significant correlation was found between the plaque volume with cTnI on day 7 (ρ=0,52, p<0,05) and the plaque burden with cTnI on day 7 (ρ=0,43, p<0,05).Conclusion. According to CTCA, the soft tissue component of plaques is associated with coronary atherosclerosis severity and myocardial damage in patients with MI. Soft tissue burden is a predictor of more severe myocardial damage, according to the cardiac biomarker data.