Microvascular obstruction (MVO) of coronary arteries increases the mortality rate and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). According to preliminary data platelets, inflammation, Ca2+ overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. Many questions related to the pathogenesis of MVO remain unanswered. The role of endothelial cell damage in the formation of MVO in patients with AMI and PCI is unknown. It is unclear whether nitric oxide (NO) production reduces or decreases sensitivity of smooth muscle cells of coronary arteries to NO in patients with MVO. It was obtained only indirect evidence on the involvement of inflammation in the development of MVO. The role of ROS in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied.
The significance of thromboxane A, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is unknown before. It was not obtained conclusive evidence on the involvement of coronary artery spasm in the development of MVO. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI was not performed. It is not clear whether endogenous adrenaline exacerbates MVO or, conversely, prevents MVO.

Heart rhythm disorders (HRDs) are one of the most complex and urgent problems in both adult and pediatric cardiology. One of the important points of research in the field of arrhythmology is the study of the mechanisms of HRD formation. The mechanisms that trigger arrhythmias in children have their own peculiarity associated with the age-related aspects of the formation of both the cardiovascular system and the systems responsible for its regulation, primarily the autonomic nervous system (ANS). The article presents current literature data on the contribution of the ANS to the formation of arrhythmias and the information content of its markers depending on age.

In half of cases during coronary angiography (CAG), obstructive coronary artery lesions aren’t detected in patients with chronic coronary artery disease. Such patients mostly have vasospastic angina (VSA) and/or microvascular angina (MVA). These patients can be performed repeated diagnostic tests, including selective coronary angiography, but as a result they are never diagnosed correctly. This review presents modern pathogenetic mechanisms for the development and methods of diagnosing of ischemia with non-obstructive coronary artery disease. It also highlights choice of treatment tactics in accordance with the identified pathophysiological mechanism for the development of chronic coronary artery disease.

 Heart failure (HF) is a highly prevalent syndrome characterized by etiological and clinical heterogeneity. This review highlights the genetic mechanisms underlying the development of this pathological condition. The results of recent genetic studies confirm the etiological complexity and clinical  heterogeneity of HF. Identification of rare pathogenic variants underlying the development of HF among patients and their relatives is important for the  timely adjustment of lifestyle and the implementation of preventive measures to reduce the risk of this syndrome and its complications. 

Currently catheter radiofrequency ablation (RFA) has become the standard treatment for patients with atrial fibrillation (AF). During RFA, additional linear lesions are performed along the posterior wall of the left atrium, which can cause damage to the esophagus. The manuscript considers the methods introduced into practice to prevent damage to the esophagus during RFA, the pros and cons of the techniques.

Acute myocardial infarction (AMI) is one of the main causes of mortality among the able-bodied population in Russia and the population of economically developed countries. In recent years, deaths from AMI in the USA and Europe have not decreased. This is due to the lack of highly effective drugs for the treatment of AMI. One of the promising drugs to improve the survival of patients with AMI is erythropoietin. We searched for full-text publications in the PubMed database and on the website of the journal Nature. In studies performed on animals, it was shown that erythropoietin (5000 U/kg) is able to increase cardiac tolerance to ischemia and reperfusion due to activation of a number of kinases (PKC, ERK1/2, Akt, JAK2, PI3K) and due to GSK-3β kinase inactivation. Erythropoietin prevents post-infarction remodeling of the heart and enhances the process of myocardial neovascularization in rats and dogs. Erythropoietin in used doses (on the average 1000 U/kg) does not affect infarct size in patients with AMI and does not have an effect on post-infarction ventricular remodeling in humans. The reason for this discrepancy between experimental and clinical data remains unclear. It is possible that the use of large doses of erythropoietin or the use of its analogues that do not affect erythropoiesis can prevent the development of post-infarction cardiac remodeling in humans.

Relevance. Pathology of non-infectious genesis is currently playing a leading role in the structure of overall morbidity of the population. The incidence of inflammatory bowel diseases increases all over the world. The severity of inflammatory bowel diseases complicates the presence of comorbid pathology, metabolic disorders, which lead to disability and the risk of premature death. Currently available diagnostic measures allow to detect disorders at the stage of clinical manifestations. There are several factors causing the development of pathological changes at the early stage including the peculiarities of intestinal microbiome formation and the predominance of certain microorganism clusters with the subsequent formation of a biotype, which may allow diagnosing the disease at a latent stage.
Aim: To evaluate the role of the intestinal microbiota in the formation of inflammatory bowel diseases and metabolic disorders according to the data of national and foreign literature.
Material and Methods. The review of literature on this topic was carried out based on the analysis of data obtained from the publications indexed in PubMed, Web of Science, Scopus, Google Academy, and eLibrary.ru databases over the past 10 years.
Results. Data on the role of intestinal microbiota in the development of changes in patients with inflammatory bowel diseases and metabolic disorders (obesity, impaired glucose tolerance, and diabetes mellitus) were revealed. New potential mechanisms for the development of type 2 diabetes mellitus were identified, and the features of the generic composition of the flora in patients with comorbid pathology were described.
Conclusion. The obtained results suggest that further research is required to improve understanding of this pathology and to create the methods for correcting the gut microbiota in case of abnormal findings.

New coronavirus disease (COVID-19) is a life-threatening infection that can lead to the development of persisting symptoms. Clinical, radiological and histopathological characteristics of post-coronavirus pneumonia are similar to secondary organizing pneumonia (SOP). This type of pneumonia is considered to be a complication of COVID-19, which correlates with the severity of the disease and increases patient mortality rates.
It should be noted that radiological signs of pneumonia are can be observed in recovered individuals in 67% of cases. Moreover, fibrosis, complicated by symptoms of respiratory failure, may develop in 5-8% of the cases despite the fact that SOP resolves independently in 25% of individuals, and, in most cases, can be easily treated.
Currently there are no methods of treating SOP induced by COVID-19; the first-line therapy involves the use of glucocorticosteroids (GCs). Despite the effectiveness of GCs, the treatment lasts for more than six months, and the disease has a high probability of relapse upon treatment discontinuation. Clinical trials have been registered to determine the optimal treatment duration and dosages of GCs in SOP treatment after COVID-19, however, the lack of consensus remains, keeping this issue open. This review provides data regarding organizing pneumonia, SOP induced by COVID-19, its radiological signs and treatment options within the framework of ongoing clinical trials.

There is a universal trend towards increase of patients with chronic kidney disease by 7% on average. In the Russian Federation, the annual increase is even higher, at about 10%. The average age of patients receiving renal replacement therapy is 60 years in the Tomsk region and 56 years in Russia, which is relatively lower than in European countries and the United States. With increasing age of patients receiving dialysis treatment, a progressive increase in the incidence of secondary hyperparathyroidism is recorded. Mineral and bone disorders, hyperphosphatemia, hypercalcemia all lead to premature vascular calcification, increase the risk of cardiovascular complications and death. At the same time, elderly patients are characterized by an increase in risks immediately after the start of dialysis therapy. There is a global tendency towards increase in the target level of parathyroid hormone. Parathyroidectomy is recognized as a gold standard for treatment of drug-resistant hyperparathyroidism across the world. As the development of hyperplasia in the parathyroid glands does not proceed synchronously, instead progressing at different rates and in the selective glands, methods of local influence on the altered glands have recently been developed in order to gradually control secondary hyperparathyroidism. Alternative to the total parathyroidectomy are minimally invasive non-surgical methods, attractive due to a smaller number of complications, such as bleeding and paresis of the recurrent laryngeal nerve. Examples of minimally invasive methods are local injections of preparations of the active form of vitamin D, which lead to apoptosis of parathyroid gland cells instead of their destruction, and are safer in relation to surrounding tissues. This article presents current data on the prevalence of secondary hyperparathyroidism in chronic kidney disease. An analysis of clinical trials was carried out based on articles indexed in the Scopus database, the Russian Science Citation Index, PubMed and Web of Science.

Background. Acute coronary syndromes are often associated with the onset or aggravation of anxiety and depressive disorders, delirium, cerebral ischemia up to the development of a stroke.
Aim: To study the level of brain-specific protein S100B in blood plasma in patients with acute coronary syndrome (ACS) associated with anxiety-depressive disorders (ADD).
Material and Methods. The study included 81 patients with ACS and the presence of anxiety and depression. Patients were surveyed using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory, and the Sheehan Patient-Rated Anxiety Scale. All patients underwent blood sampling to study the level of S100B protein.
Results. Patients included in the study were diagnosed with clinical anxiety and subclinical depression. In 35 patients (43%), the S100B protein level varied from 0 to 90 ng/l, and in 46 patients (57%), its level was above 90 ng/l. According to correlation analysis in patients, positive correlations were found between a high level of S100B protein in the blood serum and clinical indicators (diabetes mellitus, obesity, smoking, arterial hypertension, postinfarction cardiosclerosis, a history of cerebral stroke), levels of anxiety and depression, as well as negative correlations between high level of S100B protein in blood serum and glomerular filtration rate, left ventricular ejection fraction.
Conclusions. An increase in the level of S100B protein was observed in comorbid patients with clinically pronounced anxiety and depressive symptoms. It is possible that higher values of glial protein S100B in the blood at admission in patients with ACS may predict a more severe course of cardiovascular disease and a worse neurological prognosis, but it requires further study.

Progressive or accelerated atherosclerosis is accompanied by unfavorable clinical outcomes. Studying and understanding this process and creating a personalized method for assessing the risk and prognosis of this disease are necessary to optimize approaches to treatment and prevention.
Aim: To compare two approaches to the creation of prognostic risk model of progressive atherosclerosis: non-linear regression model of logistic type and free cross-platform visual programming system Orange method.
Material and Methods. The retrospective cohort study included 202 patients with confirmed coronary heart disease: 147 men and 55 women. The mean age of the patients was 53.3 ± 7.16 years. Group 1 included patients with myocardial infarction or unstable stenocardia, emergency arterial stenting, stroke, peripheral arterial thrombosis, critical ischemia and lower extremity amputation within 2 years before inclusion in the study. Patients in the comparison group did not have these events. Predictive models of the influence of different studied parameters on the probability of rapid progression of atherosclerosis were built using factor and correlation analysis and free cross-platform Orange visual programming system.
Results. The authors’ suggested approaches to the evaluation of the risk of progressive atherosclerosis have a good prognostic accuracy (sensitivity 94.1, specificity 97.0 and accuracy 95.5 coefficients, respectively) for the regression model and 0,950 (95,0%) for the machine learning model. However, the construction of the regression model is a more complex procedure compared to the second approach, where the choice of informative indicators for the prediction model is made by Orange. Nevertheless, the above two approaches can successfully complement each other, allowing to build more accurate predictive risk models.
Conclusion. The proposed authors’ approaches to assessing the risk of progressive atherosclerosis have a good prognostic accuracy.

Despite the technological developments in the healthcare industry, cardiovascular disease mortality occupies a leading place among the structure of general mortality of the population. The use of modern treatment methods, especially, percutaneous coronary intervention, provides timely assistance to patients with acute coronary syndrome and helps to reduce mortality frequency. Currently, clear algorithms for the management of patients with ST-segment elevation myocardial infarction have been developed. However, despite it, there are paradigms in the management of patients with non-ST-segment elevation myocardial infarction (NSTEMI). This is primarily due to the fact that the vast majority of patients with NSTEMI are elderly and senile persons. This review article presented the main factors that adversely affect short- and long-term prognosis and results of clinical studies dedicated to the study of this problem.

Aim: To study serum values of GM-GSF, CCL22, CCL11 and TRAIL in patients with primary ST-segment elevation myocardial infarction (STEMI) in early and late post-MI period and their relationship with heart remodeling in 12 months after acute myocardial infarction (MI) diagnosis.
Materials and Methods. Eighty four patients with new-onset STEMI were enrolled in the study. Echocardiography was done on day 1 and in 12 months MI. Serum levels of GM-GSF, CCL22, CCL11, TRAIL and C-reactive protein (CRP), NT-pro-NP, troponin I, CK-MV were assessed on days 1 (T1), 7 (T2), in 6 (T3) and 12 months (T4). Patients with adverse left ventricle (LV) remodeling were classified as group 1, and patients with adaptive LV remodeling were classified as group 2 in 12 month of follow-up.
Results. 64 patients underwent a 12-month follow-up, of which adverse LV remodeling developed in. Patients from group 1 showed significantly higher levels of markers of myocardial necrosis (CPK MB, troponin I) on the first day of MI and NT-proBNP at all points of the investigation than in patients from 2nd group, p < 0.05. Analysis of the chemokines revealed, that the serum concentration of GM-CSF at the points Т2, Т3, T4 and TRAIL at points T1, T4 were significantly higher, and CCL22 at all of the study and CCL11 at T1, T2, T3 significantly lower than patients from group 2, p < 0,05. According of multiple linear regression predictors of LV dilatation by the 12th month of MI were the serum levels of GM-CSF (p = 0,004), NT-pro-BNP (p = 0,009) on the 7th day of MI and the age of patients (p = 0,005).
Conclusions. In patients with adverse LV remodeling have higher levels of circulating GM-GSF, TRAIL and lower levels CCL11, CCL22 in early and late post-MI period. Among the studied inflammatory biomarkers, only the level of GM-CSF on the 7th day of STEMI showed an independent relationship with late adverse LV remodeling.

Background. Studies of the role of cytokines in the pathogenesis of coronary artery disease (CAD) are quite relevant. Significant cytokine imbalance is mostly observed in patients with acute coronary syndrome. However, there are limited reports of serum cytokine levels in patients with chronic stable CAD. The problem of relationship between cytokines to the severity of coronary atherosclerosis is still urgent.
Aim: To investigate the relationship between serum levels of cytokines and the severity of CAD.
Material and Methods. Serum levels of IL-2, IL-4, IL-6, IL-10, TNF-a was analyzed in 24 healthy control patients and 70 patients with stable CAD who underwent coronary angiography. Coronary atherosclerosis was assessed with Gensini scoring system. Depending on the median of GS (38.0), the patients were divided into moderate CAD group (GS = 8–37) and severe CAD group (GS ≥ 38). The data were analyzed using Statistical Package for the Social Sciences (SPSS) software 26.0.
Results. Patients with obstructive CAD presented higher TNF-α levels and lower IL-4. Patients with severe CAD increased IL-6 and reduced IL-2 levels. Logistic regression analysis showed that the IL-6 was independently related to the presence of obstructive CAD (OR = 3.836; 95% CI= 1.8–8.177). ROC analysis of the IL-6 logistic regression model showed that a cut-off of 5.19 pg/mL had 75.0 % sensitivity and 70.0 % specificity to predict severe atherosclerosis.
Conclusion. Pro-inflammatory TNF-α and IL-6 cytokines increased, while regulatory IL-2 and anti-inflammatory IL-4 decreased in patients with stable CAD. Cytokine imbalance contributes to CAD progression. Elevated IL-6 levels and the pro-inflammatory potential of the blood increases in case of severe coronary atherosclerosis. It has been shown that with an increase in IL-6 levels, the odds of detecting severe CAD increases 3.5-folds.

Aim: To evaluate the efficacy and safety of the preventive use of glycoprotein (GP) IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction (STEMI) and a high risk of «no-reflow» phenomenon.
Material and Methods. A total of 100 patients were included in the study. For all patients, the risk of no-reflow was calculated using a previously developed scoring system. In case of high risk, GP IIb/IIIa inhibitors were administered according to the decision of the interventional cardiologist. The rate of no-reflow as well as the rates of death, recurrent myocardial infarction and stent thrombosis were analyzed.
Results. High risk of no-reflow was determined in 37 patients, low risk of no-reflow – in 63 patients. In the high-risk group 22 patients (59.5%) GP IIb/IIIa inhibitors were preventively used. In these patients, the frequency of no-reflow was lower compared with high-risk patients who did not receive preventive GP IIb/IIIa inhibitors (9.1 vs. 46.7%, p = 0.017). With the preventive use of GP IIb/IIIa inhibitors in high-risk patients, the rates of no-reflow (9.1 vs. 11.1%, p = 1.000) and angiographic success of percutaneous coronary intervention (72.7 vs. 84.1%, p = 0.341) were comparable with low-risk patients.
Conclusion. The preventive use of GP IIb/IIIa inhibitors in patients with STEMI and a high risk was associated with reduction of «no-reflow». In the prophylactic use of GP IIb/IIIa inhibitors in patients with STEMI and a high risk of no-reflow, the results of their treatment were comparable to patients with a low risk of no-reflow.

Background. The ejection fraction (EF), diastolic dysfunction of the left ventricle (LV) and its volumes play the main role for prognosis assessment. Measurement of left atrial strain is a new method of noninvasive investigation of mechanical function.
Aim: To investigate the mechanical function of the left atrium in patients with acute myocardial infarction (AMI) with different degrees of left ventricular ejection fraction reduction.
Methods. We studied 60 patients with acute ST-segment elevation anterior myocardial infarction. Echocardiography was performed in the first day of acute infarction. The left atrium was assessed by phase volumes, as well as by strain and strain rate using speckle-tracking. 35 healthy subjects were investigated for control. The patients were divided into 4 groups: Group 1 – LV EF 50–60%, Group 2 – LV EF 40–49%, Group 3 – LV EF 30–39%, Group 4 – LV EF 20–29%.
Results. There were no significant differences in left atrial volumes between patients in groups 1–3 and healthy patients. Left atrial volume was increased in the fourth group. In the first group, peak longitudinal atrial strain (PALS) was significantly reduced compared with control group (PALS 22% vs 32.4%, p < 0.000). In the second group PALS was 17.41%, in the third group it was 18.19%. In the group with LV EF less than 30%, PALS was 4.43%. In healthy subjects, the strain rate was – 2.14 cm/s-1, in Group 1 – 2.15 cm/s-1 (p < 0.297), in Group 2 – 1.19 cm/s-1(p < 0.000), in Group 3 – 1.58 cm/s-1 (p < 0.000), and in Group 4 – 1.14 cm/s-1(p < 0.000).
Conclusion. In patients with AMI with LV EF more than 50%, significant violations of LA strain are detected, which may be a predictor of left heart dysfunction. As the LV EF decreases, LA strain decreases and LA volume increases.

The spleen is one of the main reservoirs of monocytes, the leading cells of the post-infarction inflammatory response.
Aim: To assess features of splenic macrophage infiltration, its dynamics and correlations with myocardial macrophage infiltration and an adverse course of the myocardial infarction (MI)
Material and Methods. The macrophage composition of spleen and myocardium sections of patients (n = 30) with fatal MI and persons from the control group without cardiovascular disease (n = 5) was assessed by immunohistochemistry.
Results and conclusion. All investigated cells, as CD68+, CD163+, CD206+, and stabilin-1+ were represented in the spleen regardless of the presence of MI. Their number in spleen in patients with MI remained consistently high regardless of the period of MI, and was accompanied by an increased number of such cells in the infarction area of myocardium. CD68+, CD163+ and stabilin-1+ cells predominated in the red pulp in patients with fatal MI, its number many fold exceeded that in the control group and that in the white pulp and in the infarction area of myocardium. In the white pulp of patients with fatal MI, the number of CD68+ cells predominated, in persons from the control group – CD163+. We revealed only one cell types whose content in the spleen in the control group was higher than in individuals with fatal MI – CD206+in the red pulp. Low content of CD206+ cells in the red and white pulp of the spleen characterized patients with a fatal outcome of MI.

Introduction. Searching of highly specific, sensitive and easy-to-use markers of multiple organ failure (MOF) that will help to the early prognosis of this unfavorable condition, prevent complications and reduce mortality in the early postoperative period is very urgent for the modern medicine.
Aim: To study the pathogenetic significance of the TREM-1 gene polymorphism in MOF in patients with coronary artery disease (CAD) in the early postoperative period.
Material and methods. 592 CAD patients (564 patients with uncomplicated postoperative period and 28 MOF patients) were selected for the presented study. Genotyping polymorphic variants rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535 and rs2234237 in the TREM-1 gene was carried out by polymerase chain reaction.
Results. It was found that the allele T (rs2234246), the allele G (rs1817537) and the allele T (rs3804277) in the TREM-1 gene were associated with an increased MOF risk after elective surgery according to the dominant inheritance model. TREM-1 polymorphic loci rs7768162 and rs4711668 were associated with a decreased MOF risk according to the additive inheritance model. We found no significant associations between polymorphic variants rs2234237, rs6910730, rs9471535, as well as inherited haplotype and MOF risk. Using the MDR analysis, three most significant models of gene-gene interactions of TREM-1 polymorphic loci associated with MOF risk in patients after cardiac surgery were identified.
Conclusion. The obtained results demonstrate a significant contribution of polymorphic variants in the TREM-1 gene to the development of MOF in patients undergoing cardiac surgery.

Aim: evaluate clinical and structural-functional characteristics, including adverse events and outcomes, in patients with noncompact cardiomyopathy (NCM) with various genetic variants.
Material and Methods. 51 unrelated patients with NCM were examined (mean age 37 [28; 47]; men (54.9%), women (45.1%)), observed for 7 to 211 months (in average 38 months). Clinical and instrumental examination included checkup, collection of individual and family history, ECG-12 registration, 24-hour Holter ECG monitoring, echocardiography, magnetic resonance imaging (MRI) of the heart with late contrast enhancement. The search for mutations in the coding sequences of 174 genes associated with cardiovascular pathology was carried out by high-throughput sequencing (NGS).
Results and discussion. In 24 of 51 (47.1%) patients, 27 mutations of pathogenicity classes IV and V were detected, while in 21 (41.2%) patients, mutations were in the genes of sarcomeric proteins, of which 37.5% were in the MYBPC3 gene, 25.0% in the MYH7 gene, and in the TTN gene, leading to a shortened protein (TTNtv) – 33.3%, there is a mutation in the ACTC1 – 1 gene (4.2%). In 5.9% of patients, mutations were detected in genes encoding structural proteins and ion channel subunits. Two or more genetic variants were found in 10 out of 24 (41.7%) patients. No significant genetic variants were identified in 14 (27.4%) patients. Patients with mutations in the TTNtv gene were associated with severe systolic dysfunction, dilation of the left ventricle. Carriers of mutations in the MYBPC3 gene and several genetic variants were more likely to have adverse events and outcomes: progression of chronic heart failure (CHF), ventricular tachyarrhythmias, sudden cardiac death (SCD) with successful resuscitation, mortality. Patients with mutations in the MYH7 gene had no adverse outcomes.
Conclusion. Comparative analysis showed that patients with NCM had the most severe form of the disease with significant clinical manifestations, episodes of clinical death with subsequent resuscitation and cardioverter defibrillator implantation in probands with mutations in TTNtv gene, mutations in the MYBPC3 gene or multiple genetic variants.

Background. Bioprosthetic heart valves (BHVs) are prone to the proteolytic degradation, eventually resulting in their degeneration and failure. Previously, we found cysteine cathepsins with a collagenase and elastase activity in bioprosthetic tissue but it remained unclear whether they precipitated from the circulating blood or have been produced by the infiltrating host cells.
Aim: To study the distribution of cathepsin B, cathepsin K, cathepsin L, cathepsin S, cathepsin V, and cathepsin Z in bioprosthetic heart valves and to identify their source.
Material and Methods. We examined five BHVs excised from the mitral position during the repeated heart valve replacement. Average duration of BHV functioning was 169 ± 31 months. Consecutive sections from the degenerated BHV segments were investigated by Russell-Movat’s pentachrome staining and immunohistochemistry, employing antibodies to leukocyte markers (pan-leukocyte marker CD45, macrophage marker CD68, neutrophil marker myeloperoxidase, T cell marker CD3, and B cell marker CD19) and cathepsins (B, K, L, S, V, and Z).
Results. Macrocalcification and tears were the most frequent degenerative alterations found in BHV leaflets. Further, BHVs were notable for the fragmentation of collagen fibers at and beneath the surface, and were devoid of elastic fibers and mucopolysaccharides. Macrophages were co-localised with the degraded extracellular matrix foci. Cathepsin B was detected only in macrophages whilst other cathepsins (K, L, S, V, and Z) were expressed both in the immune cells and extracellular matrix.
Conclusion. Macrophages are capable of producing all cysteine cathepsins in BHV leaflets. Localisation of cathepsins K, L, S, V, and Z in the extracellular matrix also indicated blood as their major source.

Background. Currently pacing is the only treatment option for life-threatening bradyarrhythmias. Considering the specific factors of pediatric patients, specialists in this field should be highly professional.
Aim: To present the experience and retrospective analysis of complications of permanent pacing in children and adolescents from Tomsk National Research Medical Center.
Material and Methods. Complications of permanent pacing in children with structurally normal heart and children with congenital heart defects were analyzed. The follow-up was from 1999 to 2021 years. 256 patients aged from 1 month to 18 years participated in the study. Epicardial pacemaker was implanted in 173 children, endocardial – in 83 patients. Average time from primary implantation to complications was 2.1 ± 2.7 years.
Results. Hemodynamic complications are the most common among patients with epicardial and endocardial permanent pacing. Hemodynamic complications with epicardial permanent pacing are associated with intraventricular dissynchrony due to stimulation in the area of the lateral wall or the right ventricular outflow tract. In patients with endocardial permanent pacing hemodynamic complications are associated with the development of pacemaker-induced cardiomyopathy due to permanent pacing of the right ventricle apex and tricuspid regurgitation. Complications such as bacterial endocarditis, infection of the pacemaker and its bed, hemopericardium, subclavian vein occlusion, pericarditis, peacemaker dislocation and lead fracture were less common. Two cases of cardiac strangulation were detected.
Conclusion. Neither epicardial nor endocardial pacemaker implantation guarantee the absence of complications. Implantation of the electrode on the apex of the left ventricle (epicardial pacemaker system), in the area of the His bundle (endocardial pacemaker system), prevents the development of hemodynamic complications. The most rational is the use of a primary epicardial pacemaker system. Such approach allows the veins to be preserved for endocardial stimulation at an older age.

Aim: To test the previously developed predictive model on a test set, including patients with non-valvular atrial fibrillation (AF).
Material and Methods. A predictive model was previously developed on a training set of 638 patients with non-valvular AF. The test set included 175 randomly selected patients with non-valvular AF hospitalized at the Tyumen Cardiology Research Center for radiofrequency ablation (RFA) or electrical cardioversion in 2018-2021. The quality of the predictive model was assessed using ROC analysis.
Results. Arterial hypertension, coronary heart disease, congestive chronic heart failure, and persistent AF were more common in patients of both sets with left atrial appendage (LAA) thrombosis. Patients of the training and test sets with LAA thrombus had more pronounced structural changes in the heart cavities and similar changes in the geometry of the heart: normal left ventricle (LV) geometry was less common and eccentric LV hypertrophy was more common. According to the results of a previous retrospective analysis of the data, independent predictors of LAA thrombosis were persistent type of AF, left atrium size, and eccentric LV hypertrophy. Based on the data gathered, a predictive model LAA thrombosis was developed as an equation that includes 3 variables. The cut-off point for calculating the probability of LAA thrombosis is 0.07. Applying this model on a test set showed the good quality of the model: the area under the curve obtained using ROC analysis was 0.750 (p < 0.001). At the same time, the sensitivity and specificity of this model for the detection of LAA thrombosis were 72.3% and 71%, respectively.
Conclusion. The evaluation of the quality of the LAA thrombosis predictive model developed on the training set confirmed its good quality on a similar test set of patients with non-valvular AF hospitalized for RFA or electrical cardioversion.

Aim: To study the clinical and functional features, as well as intra- and postoperative indicators of patients with chronic thromboembolic pulmonary hypertension (CTEPH) with the development of negative dynamics of cognitive status in the early postoperative period and to identify pathophysiological factors associated with this disorder.
Material and Methods. The study included patients with CTEPH scheduled for pulmonary endarterectomy (PEA). The 1st group (38 people) consisted of patients with the development of negative dynamics of cognitive functions according to the MMSE scale in the early postoperative period, the 2nd group (91 people) – without negative dynamics of cognitive functions. Preoperative clinical, anamnestic data, intraoperative parameters, early postoperative complications and their relationship with the negative postoperative dynamics of cognitive status were analyzed.
Results. The average age of patients in the general group was 54.1 (44.3–68.1) years. The 1st group was characterized by older age (p = 0.03), a prevalence of patients with diabetes mellitus (p = 0.02), arterial hypertension (p = 0.04), atherosclerosis of the brachiocephalic arteries ≤ 50% (p = 0.04) and higher level of Charlesson comorbidity index (p = 0.002) in comparison with the 2nd group. Intraoperative factors for the development of postoperative cognitive impairment were a longer circulatory arrest (CA) during PEA and a more pronounced decrease in cerebral oxygenation during CA. The 1st group of patients were characterized by a large number of complications, including pulmonary heart failure (p = 0.02), acute renal failure (p < 0.001) and atrial fibrillation (p < 0.001) in comparison with the 2nd group. The development of negative postoperative dynamics of cognitive status in CTEPH patients was associated with baseline reduced cognitive function – OR 2.3 (1.4–9.2 95% CI) (p = 0.01) and with the presence of three or more CA during PEA – OR 3.2 (1.1–12.7 95% CI) (p = 0.01).
Conclusion. Independent factors for the development of negative postoperative dynamics of cognitive status in patients with CTEPH were baseline impairment of cognitive function (< 20 points according to the MMSE scale), three or more CA during PEA, and the development of new-onset atrial fibrillation in the early postoperative period.

Actuality. Currently there are no long-term studies about the course of multiple sclerosis (MS) after coronavirus disease 2019 (COVID-19), in comparison with healthy volunteers who recovered from COVID-19 and patients with MS who didn’t have COVID-19.
Aim: To study effect of COVID-19 on MS course.
Material and Methods. We examined 39 patients with MS who recovered from COVID-19 (40.76 ± 11 years), 21 patients with MS who didn’t have COVID-19 (38.1 ± 12 years) and 33 healthy volunteers who recovered from COVID-19 (39.7 ± 10 years). We performed neurological examination and testing according to clinical and neuropsychological scales.
Results. The majority of MS patients had a mild form of COVID-19 (22 people, 68.75%). Among the symptoms of COVID-19 in MS patients, headaches (12 people, 30.8% vs. 18 people, 54.5%) and chest pain (2 people, 5.1% vs. 9 people, 27.3%) were less common than in the control group of healthy volunteers. The duration of the disease, the age of onset, the average frequency of exacerbations, the use of disease modifying therapies, the result on clinical and neuropsychological scales did not show statistically significant differences between the two groups of patients with MS. The incidence of post-COVID syndrome in patients with MS was 79.48% and 88.44% in healthy volunteers. Among MS patients who had COVID-19, there were significantly more persons with a moderate decrease in the quality of life, higher fatigue scores compared to healthy volunteers, but less apathy compared to patients without COVID-19 with MS. The presence of vaccination reduced the risk of COVID-19 infection by 7.4 times in patients with MS.
Conclusion. There was no significant effect of COVID-19 on patients with MS during short-term follow-up.

Taking into account the lack of consensus between different scientific groups on the nature and unity of the pathomorphological substrate of non-alcoholic and metabolically associated fatty liver diseases, there is a need to find new instrumental methods for their differential diagnosis in order to develop the correct treatment and monitoring tactics.
Aim: To assess the possibilities of using the complex application of instrumental diagnostic methods for the differential diagnosis of metabolically associated and non-alcoholic fatty liver disease.
Methodology and Methods. The study involved 94 patients of a multidisciplinary hospital with a combination of ultrasound signs of liver steatosis according to the B-mode. As part of the two stages of the diagnostic examination, clinical, laboratory and instrumental methods were used, including a block of ultrasound diagnostics (assessment of the thickness of visceral fat, quantitative liver steatometry, two-dimensional elastography of shear waves of the liver), dual-energy X-ray absorptiometry in the “Whole body” mode. The control group included 78 patients without signs of hepatic steatosis according to B-mode ultrasound.
Results. All patients were divided into groups according to signs of metabolic syndrome, with subsequent distribution into conditional groups of patients with non-alcoholic and metabolically associated fatty liver disease, highlighting the main signs of both diseases. Metabolic syndrome was detected in 24 women (29.27%), 18 men (21.95%). In 53 patients (64.63%), the presence of hepatic steatosis was quantitatively confirmed, of which 39 patients were found to be overweight or obese (47.56%).
Conclusion. Indicators of the instrumental assessment of the metabolic status and a complex diagnostic algorithm were determined, allowing for differential diagnosis between non-alcoholic and metabolically associated fatty liver disease with a quantitative assessment of liver steatosis.

Aim: To study the effect of new synthesized pyrimidine derivatives on the growth of Mycobacterium lufu (M. lufu) and Mycobacterium tuberculosis (M. tuberculosis) when cultivated on Shkolnikova’s medium.
Materials and methods. The objects of research were new synthesized derivatives of 6 samples of derivatives of pyrimidine - 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-trions under laboratory codes TAG1, TAG2, TAG3, TAG4, TAG5, TAG6 and 7 samples of 5-(getarylmethylidene)-2,4,6-pyrimidine-2,4,6(1H, 3H, 5H)-trions under the laboratory codes TAG7, TAG8, TAG9, TAG10, TAG11, TAG12, TAG13. M. lufu and M. tuberculosisH37Rv strains were used as test cultures. The antimycobacterial activity of the studied compounds was studied by the method of serial dilutions.
Research results. All studied compounds were found to exhibit antimycobacterial activity. The greatest inhibitory effect against M. lufu was noted for TAG1, TAG4, TAG7, TAG12, and TAG13, which was comparable to that of the reference drug dapsone. By the nature of the inhibitory effect on the growth of M. tuberculosis, the compounds under the laboratory codes TAG 1, TAG 4, TAG 7 and TAG13 were comparable to isoniazid, and the effect of the TAG3 compound was even slightly superior to the reference drug.
Conclusion. Among the studied new synthesized pyrimidine derivatives, compounds under the laboratory codes TAG1, TAG4, TAG 7 and TAG13 have the most pronounced antimicrobial activity both against M. lufu and M. tuberculosis, which allows us to consider them as the most promising substances for further research on the search for antimycobacterial, including antileprosy drugs.

Introduction. Chronic constipation is one of the most actual problems in modern coloproctology and found in 14–16% of developed countries population. The causes of chronic constipation vary widely from functional to organic. The latter include dolichocolon, different variants of which occur in 16% cases.
Aim: To give a morphological and quantitative characteristic of the decompensated stage of dolichocolon based on the morphogenesis of changes in comparison with the histologically normal colon.
Material and Methods. Colon tissue samples from 16 people were used and divided into two groups. The first, control group, included 8 sectional cases of a morphologically normal colon wall. The second, the study group, was represented by surgical material from 8 patients with dolichocolon decompensated stage. Observation groups were comparable by sex and age.
Results. In average, in patients with the decompensated dolichocolon stage, in comparison with the control group, statistically significantly (p ˂ 0.05), the thickness of the mucous and muscular membranes decreases by 1.07 and 2.26 times, respectively. The thickness of the submucosa increases by 1.17 times. However, the maximum and minimum values of this parameter change only by 1.35 times, while in the control group – by 7.21 times, as a consequence of the development of insufficiency of the evacuation-motor function of the colon which indicates the maximum smoothness of the colon wall, and is a consequence of its functional insufficiency. The specific proportion of neuro plexuses in the muscular membrane is 1.45 times higher than in the control group. However, the number of nerve cells decreases by 2.98 times, as a result of the development of insufficiency in the evacuation-motor function of the colon. The average area of lymphatic follicles decreases by 1.49 times, and secondary follicles disappear altogether, meaning the depletion of the compensatory-adaptive reactions of the lymphoid apparatus.
Conclusion. Morphological and morphometric signs of irreversible changes, such as dystrophy, atrophy and sclerosis of all structural elements of the thick wall in the stage of decompensated dolichocolon, suggest surgical treatment, as well as prevention of the development of decompensation of the general condition of patients.

 Remote monitoring systems of implanted antiarrhythmic devices are becoming a common method of functioning monitoring with the possibility of recording arrhythmias and transmitting data to a doctor, along with routine checks in medical institutions. It is important to inform patients about possible unscheduled visits to the hospital if necessary and to be in touch with them. In the clinical case presented below, the patient did not feel the shock discharge of the implanted cardioverter-defibrillator and did not contact the clinic. The alarm notification received by the doctor and the subsequent analysis of the remote monitoring data made it possible to identify and promptly eliminate the dislocation of the defibrillation lead in a hospital. 

 A literature review is presented with an analysis of a clinical case of a patient with a combination of Brugada syndrome (BS) and myocardial infarction without obstructive coronary artery disease ((MINOCA). The presence of BS in a patient does not exclude the development of myocardial infarction. The article discusses the difficulties of differential diagnosis of BS and Brugada phenocopies in patients urgently admitted to the cardiology department with recurrent chest pain and a diagnosis of acute coronary syndrome with ST segment elevation. Careful history taking, analysis of the electrocardiogram dynamics, and invasive coronary angiography contributed  to the identification the combination of BS and MINOCA in the patient. 

The article presents a case report of Stevens-Johnson syndrome (SJS), a rare but serious pathological process with erosive mucosal lesions and widespread skin lesions. SJS is usually caused by an allergic reaction to  medications, sometimes triggers of the syndrome are infectious diseases, but often the cause cannot be determined. A disease, especially drug-induced,  can occur in practice of any specialty physicians. But it is not always  recognized in time. It often requires an individual approach to treatment. The presented clinical case confirms a need for timely diagnosis, early initiation of individual treatment. 

COVID-19 is especially severe in patients with a premorbid background.
Aim: To describe a clinical case of SARS-CoV-2 infection complicated by bilateral viral pneumonia, cardiogenic pulmonary edema, and dilated сardiomyopathy.
Clinical case. Patient M.V., 76 years old, from 02.11.2022 to 03.11.2022 was hospitalized at the Republican Cardiological Dispensary with a diagnosis of Bilateral viral pneumonia, the percentage of damage was 75%. Acute respiratory distress syndrome, severe. Complaints at admission: lack of air in a horizontal position, fever up to 38,0 °С, dry cough. Computed tomography of the chest was performed; bilateral viral pneumonia was determined (75% of lesions). PCR smear for coronavirus infection was positive. Determination of troponin T from 02.11.2022: 0.022 ng/ml. History: hypertension for many years with maximum blood pressure of 190/100 mm Hg, acute myocardial infarction of the anterior wall of the left ventricle with ST segment elevation (November 20, 2021), percutaneous coronary intervention (November 20, 2021). The above complaints were noted within a week. On the second day of inpatient treatment, a lethal outcome occurred. She was sent for a post-mortem examination. In the lungs, histological examination revealed a violation of microcirculation in the form of erythrocyte sludge, stasis. Widespread atelectasis/dystelectasis. There was intraalveolar edema. On macroscopic examination, the cavities of the heart are enlarged.Histological examination revealed large-focal cardiosclerosis, areas of wave-like deformation of myocardial muscle fibers. Virological examination of sectional material in the lungs and heart revealed SARS-CoV-2 RNA.
Conclusion. Viral infection with COVID-19 contributed to the development of decompensation of chronic heart failure in the form of arrhythmia and cardiogenic pulmonary edema in a patient with dilated cardiomyopathy.

The article presents a rare clinical case of a child of the first month of life with heart attack-like changes on the ECG and multiple rhabdomyomas in the heart, associated with tuberous sclerosis complex. The child was followed up for 11 months. The patient did not require therapy. Dynamic observation showed normalization of ECG parameters – no signs of myocardial infarction. 

Justification. One of the serious complications of acute myocardial infarction (AMI) is out-of-hospital cardiac arrest, which is associated with electrical instability of the myocardium, ventricular arrhythmias. The development of a complication in the presence of an emergency medical team requires immediate resuscitation measures, including basic resuscitation measures and defibrillation.
Aim: To present a clinical case of a patient with AMI with ST segment elevation complicated by recurrent ventricular fibrillation, hospitalized in an emergency hospital with the possibility of performing invasive interventions.
Methodology and methods of research. The analysis of anamnesis, electrocardiographic data of the patient, the results of coronary angiography and stenting of the coronary artery, echocardiography examination, Holter monitoring, laboratory studies was carried out.
Results. Patient P., female, 81 years old, was taken to the emergency hospital 2 hours and 15 minutes after the start of the clinic. At the prehospital stage, recurrent ventricular fibrillation, stopped by repeated three defibrillations. Non-contact, twice bouts of motor arousal. The council decided to conduct coronary angiography with possible stenting of the coronary arteries immediately. It was performed by femoral access on the right in 30 minutes after hospitalization. Complete occlusion of the anterior interventricular artery was revealed. Conductor recanalization and stenting of permanent residence was performed using a drug-coated stent. In the intensive care unit, drip administration of dopamine, noninvasive ventilation of the lungs, heparin administration were continued; double antiplatelet therapy, atorvastatin, amiodarone were prescribed. Since the fourth day, a beta-blocker has been added to therapy. Physical and psychological rehabilitation was carried out. She was discharged on the 15th day in a satisfactory condition.
Conclusion. Out-of-hospital cardiac death requires urgent resuscitation measures, among which defibrillation occupies a special place, as well as immediate hospitalization to a cardiology center with the possibility of performing invasive  interventions. Early rehabilitation plays an important role in the treatment of patients.

A 79-year-old woman was admitted to the emergency department of cardiology after transient loss of consciousness episode and a recorded ventricular tachycardia. The ST segment elevation in I, aVL, V1-V5 leads up to 6 mm and ST-segment depression up to 1 mm in III, aVF were registered at admission. The emergency coronary angiography showed of slowed coronary blood flow without stenosing atherosclerosis. The diagnosis of acute myocardial infarction was based on: 1. The typical progression of ECG: ST elevation resolved and the T wave become inverted; 2. The transient increasing CK up to 439 U/l, CK-MB up to 52 U/l and troponin I up to 5.8 ng/ml; 3. The inclusion of paramagnetic in the myocardium in the anterior wall and septum of LV by the type of ischemic damage. The diagnosis of Takotsubo syndrome based on rapid and complete recovery of contractility and geometry of the left ventricle (LV). At the 2nd day LV ejection fraction was 21%; the dyskinesis, akinesis of the anterior and antero-lateral walls of the left ventricle were registered. At the 7th day the hypokinesis zones was not detected. The article discusses the literature data on the frequency of combination of these diseases and possible pathogenetic mechanisms of this combination.

 The most frequent benign cardiac tumor is a cardiac myxoma with its favorite location in left atrium. The disease has no specific symptoms and requires paraclinical diagnostic methods. We report a rare case of the left atrial myxoma with dynamic mitral valve obstruction symptoms associated with rheumatic mitral stenosis and chronic obstructive pulmonary disease. There are difficulties with interpretation of the case due to similarity of clinical presentation the  diseases. 

One of the topical issues in percutaneous coronary interventions (PCI) is the stenting of extended lesions. Currently, there are two main approaches: stenting with a single long stent (SLS) and stenting with two or more overlapping stents (OS). However, due to the conical geometry of the vessel, stenting of the SLS with a large difference between the proximal and distal reference diameters of the artery may lead to worse results than stenting of the OS, due to lower device compliance to the vessel. The article presents a clinical case illustrating our proposed algorithm for making a decision in favor of SLS or OS based on data obtained using optical coherence tomography.

Patients with ulcerative colitis exacerbation associated with COVID-19 infection represent a particular group who require additional attention and follow-up due to an increased risk of thrombosis. The article presents a clinical case of a patient born in 1971 with ulcerative colitis in association with antiphospholipid syndrome. Additionally the patient had a latent inherited thrombophilia, which activation was probably caused by exacerbation of ulcerative colitis. Nevertheless, there may have been additional triggering activity of a COVID-19 infection that the patient suffered before the exacerbation of ulcerative colitis. The patient usually had a fever in the morning during an exacerbation of ulcerative colitis. During current hospitalization, fever was also presented. To clarify the cause of the fever patient’s examination was performed. Infectious and inflammatory processes, neoplasms, connective tissue diseases were excluded. However, genetic testing revealed the presence of an increased risk of thrombosis in the patient (ITGA2 C/T, ITGB3 T/C were presented). At the same time, thrombotic masses in the portal vein, subtotal thrombosis of the right hepatic branch of the portal vein, thrombosis of the upper mesenteric vein up to 30%, lower mesenteric vein up to 70% were detected during ultrasound and computer tomography (CT) examination of the abdominal cavity. It should be noted that the management of patients with exacerbation of ulcerative colitis, especially with association with COVID-19 infection, requires an individual approach considering the risk assessment of thrombotic complications. Comprehensive examination is highly recommended, including genetic testing of patients in the clinical management of such patients.

The main purpose of the health care system is to maintain and improve the health of the population. Staffing is the main resource of the health care system, which allows to achieve the set goals and objectives. In this regard, it is of interest to identify the links between the human and resource capacity of health care and the level of population health, which can indicate the rationality of implementation of health-preserving technologies.
Aim: To establish a link between the levels of resource and staff potential of the health care system and population health in the Arkhangelsk region over the period 2010–2020.
Material and Methods. Population health indicators (incidence, life expectancy at birth, total fertility rate, infant mortality, maternal mortality) and health system indicators (availability of doctors, beds, capacity of outpatient clinics, number of nurses) were used as the material. Autocorrelation functions, cross-correlation functions, autoregressive integrated moving average were used to identify relationships.
Results. Resource and staffing indicators have no significant correlation with population health levels in the Arkhangelsk region over the period 2010-2020.
Conclusion. Our study found no significant links between indicators of the resource and staff capacity of the health care system and population health in the Arkhangelsk Region over the period 2010–2020, which may be due to the qualitative and quantitative characteristics of the data used.

Background. It is the competence of making diagnostic and therapeutic decisions that is the most important in clinical practice. Digital model of treatment and diagnostic process (TDP) allows provide the remote formation of skills for decision-making.
Aim: To provide the methodological support of remote formation of competences, to improve and assess the skills of medical decision-making in cardiology.
Methods. Clinical and diagnostic information from different sources was the material for creating virtual models of TDP. Skilled cardiologists were involved to develop technical specification; knowledge engineering methods were used. Fifty virtual patients with linear structure and ten with branched structure were developed. Technical specification was implemented using Web technologies – Java Script (framework Vue.js), Twitter bootstrap, PostgreSQL.
Results. In the first phase of this project only a Web-resource was created. All digital models of patients’ TDP were placed in a linear order without any interactivity. To assess the effectiveness of medical decisions in the second phase of the project, branched TDP model with interactivity was created. It covers all stages of medical decision-making: from the patient hospital admission to his discharge. Besides the real invariant treatment of the patient, the model includes “subjunctive” process variants – “how could it be if ...” Among the interactive blocks, experts considered those leading to a change in TDP trajectory. We named them as “trigger” blocks, where the decisions influence upon TDP outcome. To assess the effectiveness of decisionmaking by learners, the rating system has been developed. It makes it possible to calculate not only general, but also particular personal ratings for certain categories of medical and diagnostic decisions.
Conclusion. This study suggests the methodology for remote formation and evaluation of doctor’s competencies, which is implemented in the format of virtual TDP models.