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Siberian Journal of Clinical and Experimental Medicine

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Vol 40, No 3 (2025)
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REVIEWS

11-18 10
Abstract

The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue of modern cardiology. Over the past 10 years, there has been no significant reduction in mortality among patients with AMI. It is quite obvious that there is an urgent need to develop fundamentally new drugs for the treatment of AMI. Glucagon-like peptide-1 receptor (GLP1R) agonists have some promise in this regard. GLP1R agonists have been shown to be able to prevent both ischemic and reperfusion injury to the heart. These compounds not only reduce infarct size, but also improve recovery of cardiac contractility in reperfusion. There is evidence that GLP1R agonists prevent adverse post-infarction remodeling of the heart. These data suggest a need of clinical trials of GLP1R agonists in patients with AMI and percutaneous coronary intervention. Inhibitors of dipeptidyl peptidase-4 which hydrolyzes glucagon-like peptide-1 to inactive peptides have similar positive effects. It has been shown that kinases, heme oxygenase-1 and NO-synthase are involved in the cardioprotective effect of GLP1R agonists.

19-27 9
Abstract

Myocardial fibrosis is closely associated with severe cardiovascular diseases, characterized by increased mortality rates worldwide. The development of myocardial fibrosis is based on the differentiation of fibroblasts into myofibroblasts, which synthesize components of the extracellular matrix in excess. A key regulator of fibroblast differentiation into myofibroblasts is transforming growth factor-beta. In recent years, close attention in the pathogenesis of fibrosis has been given to other growth factors – neurotrophins. It was recently discovered that fibroblasts express brain-derived neurotrophic factor (BDNF), and its receptors are involved in the pathogenesis of fibrosis of various organs and tissues. The role of BDNF and its receptors in the pathogenesis of myocardial fibrosis is just beginning to be studied. This review summarizes the information available in the literature (2019-2023) on the pathophysiological and pathogenetic mechanisms of the relationship between BDNF and cardiac fibrosis. Data presented in the literature showed that the mechanisms of action of BDNF in the cardiovascular system and the pathogenesis of cardiac fibrosis have common points of intersection, which makes this neurotrophin a promising therapeutic target for cardiac fibrosis. Further investigation of these aspects will allow the use of various external effects of BDNF to develop technology for the prevention of cardiac fibrosis.

28-35 11
Abstract

The article presents current ideas about the role of fibroblast growth factor 21 (FGF21) in the regulation of carbohydrate and lipid metabolism, as well as its contribution to the development of systemic inflammation in rheumatoid arthritis, both in laboratory animals and in humans. The classification of the fibroblast growth factor family, regulation of expression and receptor apparatus is considered. Positive effects of FGF21 have been noted in the form of normalization of carbohydrate and lipid metabolism, body weight; drugs analogues of FGF21 have proven themselves well as a therapeutic agent for the treatment of metabolic complications such as diabetes and fatty liver disease. At the same time, data are provided on the connection between elevated levels of FGF21 in blood serum and a number of pathological conditions, such as type 2 diabetes mellitus, coronary heart disease, obesity, non-alcoholic fatty liver disease, and end-stage renal failure. The facts about the controversial role of FGF21 against the background of systemic inflammation in patients with rheumatoid arthritis (RA) are reviewed. On the one hand, FGF21 may have a protective effect in patients with RA; on the other hand, serum FGF21 can be considered as a predictor of future decline in functional status and a potential marker for the progression of systemic inflammation in patients with RA. The prospects for using FGF21 for therapeutic purposes are assessed.

LECTURES

36-49 10
Abstract

Modern clinical guidelines (CGs), serving as the foundation of evidence-based medicine, predominantly exist in text document formats (PDF, DOC). It makes them difficult to automatically process and integrate into Medical Information Systems (MIS) and Clinical Decision Support Systems (CDSS). Physicians are forced to manually search for, analyze, and apply these recommendations, which is time-consuming process and increases the risk of missing important details. To solve this problem, the authors present a practical methodology for converting text-based CGs into machine-readable clinical guidelines through the application of ontological modeling. The key idea consists of a two-level model for their representation. The external level (for physicians) is a hierarchically structured text, familiar and convenient for reading and analysis. Key elements of this structure are “data containers,” which clearly describe observations, interventions, and the conditions for their application. The internal level (for computer systems) is a formalized knowledge graph into which the content of the “containers” is transformed. This graph, built upon medical ontologies and classifiers, can be automatically processed by a CDSS to generate personalized prompts directly during a physician's work with the Electronic Health Record (EHR).

The proposed approach, based on ontological modeling, allows for:

Firstly, integrating CGs into the physician's workflow (the CDSS can automatically analyze patient data and suggest relevant recommendations).

Secondly, enhancing treatment personalization through the automatic analysis of multiple individual patient parameters during decision-making.

Thirdly, facilitating navigation through CGs, as the structured format simplifies the search for needed information and understanding of the relationships between different recommendations. Fourthly, ensuring knowledge relevance (the process of updating machinereadable CGs when new guideline versions appear can be largely automated).

The proposed methodology has been successfully tested on relevant CGs in cardiology, and a CDSS prototype was implemented on the IACPaaS cloud platform. Converting CGs into a machine-readable format is a strategic step from a digital document archive to intelligent assistants that save physician time, reduce error rates, and promote strict adherence to the principles of evidence-based medicine at each patient's bedside.

Despite their importance, modern clinical guidelines do not contribute to the automation of clinical activities. They are presented in text formats, such as PDF and DOC, which limits their use in digital healthcare. This lecture presents a methodology for creating machinereadable clinical guidelines (MCG) to integrate them into medical decision support systems and medical information systems. The authors propose a two-level ontological model that includes an external-level ontology, which is a representation of MCGs in the form of hierarchically templated texts for doctors, and an internal-level ontology, which is a formalized knowledge graph for machine processing. The authors use a hybrid approach to create MCGs, combining the creation of structured MCGs by specialists with the use of large language models for formalization.

CLINICAL STUDIES

50-56 13
Abstract

Objective. It is well-established that rupture of lipid-rich atherosclerotic lesions in the coronary arteries (referred to as vulnerable, high-risk, or unstable plaques) with subsequent coronary artery thrombosis is the most common cause of acute coronary syndrome and sudden cardiac death. Vulnerable plaques are most accurately detected using optical coherence tomography (OCT). Given the high cost of OCT, an urgent task is to search for markers of the development of vulnerable atherosclerotic plaques in the coronary arteries based on routine examination data, which will allow developing effective strategies for the prevention of associated coronary events. In hypertensive patients potential markers may include indicators of systemic inflammation, but little information is available on this topic.

Aim: To identify potential markers of vulnerable atherosclerotic plaques in coronary arteries in patients with stable coronary artery disease and hypertension based on routine laboratory testing.

Material and Methods. The study included patients >18 years old, with a diagnosis of stable coronary artery disease and indications for OCT-guided PCI (extended/calcified/bifurcation lesions and/or diabetes), who gave informed consent to participate in the study. All patients underwent laboratory and instrumental examination in accordance with approved standards of medical care. A total of 30 patients were included in the study: aged 66.5±9.2 years (including 17 men); office BP 134.4±12.4/78.3±6.05 mmHg (systolic, SBP/ diastolic, DBP, respectively); type 2 diabetes mellitus (DM2) was detected in 30%; body mass index was 30.7±5.3 kg/m2.

Results. According to OCT data, patients were divided into two groups: group 1 (n = 19) with the presence of vulnerable atherosclerotic plaque morphology (rich lipid core, lipid plaque with lipid arc expansion>180°, presence of macrophage clusters) and group 2 (n = 11) with atherosclerotic plaques without signs of vulnerability. The groups were comparable in terms of gender, age, blood pressure, antihypertensive, hypoglycemic and lipid-lowering therapy. However, patients in group 1 had statistically significantly higher levels of fibrinogen (3.39±0.86 vs. 2.75±0.45, p = 0.038), platelet-lymphocyte ratio (119.2±31.9 vs. 84.0±30, p = 0.006) and blood creatinine (88.3±13.2 vs. 76.7±7.8, p = 0.014). According to multivariate logistic regression analysis, blood fibrinogen and plateletlymphocyte ratio were independent markers of the presence of vulnerable atherosclerotic plaques.

Conclusion. Platelet-lymphocyte ratio and blood fibrinogen levels, determined as part of a routine examination and reflecting increased activity of systemic inflammation, are markers of the development of vulnerable atherosclerotic plaques in the coronary arteries in patients with stable coronary artery disease and hypertension.

57-67 10
Abstract

Introduction. The systemic inflammatory response (SIR) that occurs in response to ischemia in patients with myocardial infarction (MI) is one of the significant mechanisms of the pathogenesis of this disease, determining its course and outcomes. The content of one of the key factors in the inflammation and regeneration process – macrophages (MFs), both in the myocardium and in target organs, as well as the relationship between the concentration of proand anti-inflammatory MFs in the early and late stages of infarction with its adverse outcomes remain poorly understood.

Aim: To comprehensively study the characteristics of macrophage infiltration of myocardial tissue, kidneys, brain and spleen in patients who died from myocardial infarction-associated shock (MI CS), and to characterize their relationship with the clinical profile of the patient.

Material and Methods. We included 25 patients with fatal MI CS. We examined fragments of spleens (red (RP) and white pulp (WP)), myocardium, kidneys and brain taken during the autopsy. Macrophage infiltration of the tissues was assessed by immunohistochemistry with usage of antibodies for the general marker of MFs – CD68 and to the M2 MFs markers – CD163, CD206, Stabilin-1.

Results. The maximum count of all studied cells was found in the RP: CD68+ 898 (807; 1049), CD163+ 898 (807; 1049), stabilin 1+ 807 (526; 985), CD206+ 11 (9; 19) cells. However, the content of all the studied cells in the RP and WP remained consistently high relative from the early to the late period of MI. In the myocardial (infarcted area), on the contrary, the concentration of all the studied cells increased relative from the early to the late period of MI: CD68+ from 59 (52; 95) to 376 (136; 634), CD163+ from 82 (34; 285) to 697 (545; 982), CD206+ from 21 (12; 43) to 99 (31; 249), stabilin-1+ from 0 (0; 1) to 126 cells (p < 0.05). The only cell type among those studied by us that showed a decrease in its concentration relative to the early to the late period of MI were CD206+ cells in the kidneys: from 6 (5; 8) to 2 (1; 2) (p < 0.005). When analyzing interorgan correlations, attention is drawn to the large number of interorgan interactions at the cellular level, mainly in the early post-infarction period. The correlation was shown between CD163+ cells in brain and age (r = –0.7, p = 0.0006).

Conclusions. A comprehensive analysis of macrophage infiltration of myocardium, kidneys, brain and spleen in patients with fatal MI CS showed that the maximum, consistently high content of the studied cells – CD68+, CD163+, CD206+, stabilin-1+ is characteristic of one of the leading organs of immunogenesis the spleen. The active course of SIR in the myocardium in patients with MI was reflected in an increase in the content of all studied cell types in the infarct area of myocardium, while a decrease in the regenerative capacity in patients with MI was reflected in a decrease in the content of CD206+ cells in the kidneys. A large number of interorgan relationships between MFs in the early period of MI, as well as the presence of relationships between the concentration of MFs in tissues and clinical data, confirms the value of conducting a subsequent comprehensive analysis of the cellular composition of infarcted myocardial tissue in combination with the dynamics of the level of serum markers reflecting the activity of the SIR in patients with MI CS.

68-75 12
Abstract

Introduction. There is a rapid increase in the prevalence of type 1 diabetes every year around the world. Often the course of this disease is complicated by the development of diabetic ketoacidosis, which significantly worsens the patient’s long-term prognosis. Aim: To study a cohort of patients with type 1 diabetes mellitus depending on the presence or absence of diabetic ketoacidosis. To compare patient outcomes and quality of life depending on the occurrence of diabetic ketoacidosis in patients with type 1 diabetes mellitus.

Material and Methods. The data of 502 patients hospitalized at the V.V.Vinogradov State Clinical Hospital for the decompensation of type 1 diabetes mellitus for the period from 2022 to 2023 were retrospectively analyzed. Clinical and anamnestic data, the results of instrumental (echocardiography and chest X-ray) examinations were evaluated, the presence or absence of diabetic ketoacidosis was established. In the long-term period, the life status of patients was established by telephone contact with the patient or his relative, and the quality of life was assessed based on the Short Form-36 questionnaire.

Results. Median time of life quality and relapses observation after discharge was 18.5 [12.4; 24.0] months. Depending on the presence or absence of diabetic ketoacidosis, patients were divided into 2 groups: the group of patients with diagnosed diabetic ketoacidosis (DKA+) included 206 patients, the group of patients without signs of ketoacidosis (DKA-) – 296 patients. Clinically, patients in the DKA+ group were younger, males were more common, and disease duration was shorter compared to the DKA– group. Telephone contact was established with 84,5% (n = 174) of patients in the DKA+ group and 82.1% (n = 243) of patients in the DKA– group. The development of a fatal outcomes was noted in 1.9% (n = 4) of cases in the DKA+ group and 1.0% (n = 3) of cases in the DKA– group (p = 0.40). According to the results of the Short Form-36 questionnaire, there were no significant differences in the assessments of the physical and mental components of health between the groups (p > 0.05).

Conclusion. Long-term outcomes in patients with type 1 diabetes mellitus and diabetic ketoacidosis were comparable to those in patients without a history of diabetic ketoacidosis. Previous diabetic ketoacidosis does not have a significant negative impact on the quality of life of patients in the long term in our trial.

76-84 11
Abstract

Introduction. Oxidative stress holds a prominent position among the complex and multifactorial pathological mechanisms of atrial fibrillation (AF). It induces structural changes in the atria, promotes myocardial remodeling and arrhythmia progression, and is associated with recurrences after interventional treatment. Currently, there is a lack of data regarding the relationship between plasma levels of oxidative stress biomarkers and the clinical efficacy of catheter ablation for AF in patients with cardiac arrhythmias.

Aim: To assess levels of laboratory biomarkers of prooxidant and antioxidant status in the blood plasma of patients with AF and their relationship with the effectiveness of interventional treatment.

Material and Methods. The study included 39 patients with idiopathic AF hospitalized for interventional treatment by radiofrequency ablation (RFA) of the pulmonary vein ostia. Quantitative determination of biomarkers in the blood was performed by enzyme-linked immunosorbent assay (ELISA) before the surgery. Data on AF relapses and the time of their onset were collected and analyzed for 3 months.

Results. The patients were divided into groups: 1st gr. – paroxysmal AF, 2d gr. persistent, 3d gr. long-term persistent. In all groups, the PerOx level corresponded to a high degree of oxidative stress. In 1st gr. and 3d gr., the relationships between PerOx and the CRP level are shown. An increase in the duration of the disease period was associated with a decrease in the concentration of Gpx1 in the 1st gr. For 2d gr., the relationship of PerOx with the age of patients is shown. The effectiveness of RFA did not differ significantly between the groups and amounted to 78,6, 75 and 84,6%, respectively. The relationships of biomarkers with the development of arrhythmia recurrence after RFA are shown. In 1st gr., in patients with episodes of arrhythmia, the PerOx level was higher compared to other forms of AF.

Conclusion. Measuring biomarkers reflecting systemic oxidative stress and antioxidant status in patients with AF is a promising tool for monitoring and evaluating the effectiveness of interventional arrhythmia treatment.

85-93 65
Abstract

Introduction. Glycemic control is a primary goal in the prevention of vascular complications in diabetes mellitus. Diabetic retinopathy is a common complication of diabetes mellitus. Ultrasound diagnostics makes it possible to safely assess changes in retrobulbar blood flow during glycemic control in patients with type 1 diabetes mellitus at a young age.

Aim: To evaluate association between glycemic control parameters and hemodynamic changes in retrobulbar blood flow in patients with type 1 diabetes mellitus at a young age.

Material and Methods. The study included data from 161 children aged 7–17 years with type 1 diabetes mellitus and glycosylated hemoglobin level more than 7.5%. All patients underwent ophthalmic ultrasound examination. Glycemic control was assessed using flash glucose monitoring technology.

Results. The study showed a statistically significant difference in glycemic control (p < 0.05) in patients with reduced retrobulbar blood flow comparing with a group of patients with unchanged blood flow through the retrobulbar vessels. Patients with reduced retrobulbar blood flow were characterized by an increase in the percentage of glycemic events above and below the target glycemic range (p = 0.000) and a decrease in the percentage of glycemic events within the target glycemic range (p = 0.000). A correlation was established (p < 0.05) between changes in glycemic control indicators and a decrease in blood flow through the retrobulbar vessels.

94-104 9
Abstract

Background. A significant proportion of patients with coronary artery disease (CAD) require myocardial revascularization. Arterial hypertension (AH), as a major risk factor for CAD, may influence the extent and severity of coronary artery (CA) lesions. However, visual assessment of coronary stenosis based on angiographic imaging does not always reflect their true hemodynamic significance. Therefore, the use of invasive functional assessment methods, such as the instantaneous wave-free ratio (iFR), is recommended for quantifying the ischemic potential of borderline stenosis. At present, there are no established clinical predictors for identifying functionally significant coronary lesions. Developing predictive models based on clinical, laboratory, and non-invasive imaging parameters may enhance decision-making regarding myocardial revascularization and the management of modifiable risk factors.

Aim: To evaluate the associations between the functional significance of CA stenosis and clinical, laboratory, blood pressure (BP), and epicardial adipose tissue (EAT) parameters in patients with stable CAD and HT.

Material and Methods. The study included 82 patients (56 men; mean age 66.1 ± 8.5 years) with stable CAD and HT, all of whom had borderline (50–90%) CA stenosis identified by coronary angiography. All participants underwent comprehensive clinical and laboratory assessment, transthoracic echocardiography, 24-hour ambulatory BP monitoring (ABPM), computed tomography (CT) for EAT volume and density evaluation, and iFR measurement to determine the functional significance of coronary stenosis.

Results. Patients were divided into two groups based on iFR values: those with functionally significant stenosis (iFR ≤ 0.89; n = 58) and those without (iFR > 0.89; n = 24). Both groups were comparable in baseline clinical and laboratory parameters. Patients with functionally significant stenosis demonstrated significantly higher clinical systolic BP (SBP), 24-hour SBP, and pulse pressure; greater daytime SBP load; reduced heart rate variability; a higher percentage of blood monocytes; lower prevalence of abdominal obesity; and smaller left atrial (LA) size. Multivariate logistic regression analysis, confirmed by ROC analysis, identified clinical SBP, monocyte percentage, and LA size as independent predictors of functionally significant stenosis.

Conclusion. In patients with stable CAD and HT, the presence of functionally significant CA stenosis is associated with elevated SBP, increased monocyte count, and smaller LA size.

105-113 12
Abstract

Background. Clinical suspicion of unstable angina in patients with previously unverified coronary artery disease (CAD) has limited efficacy in decisions whether invasive coronary angiography is necessary. A likelihood-based approach to selecting the optimal diagnostic test in evaluating chest pain offers distinct clinical benefits, but decision points for noninvasive angiography or functional testing for lowand intermediate-risk acute chest pain patients with previously unverified CAD remain undefined.

Aim: To find decision-making point to select stress-echocardiography (SE) as the initial test in lowto intermediate-risk acute chest pain patients with previously unverified CAD.

Methods. The study included 129 patients, aged 56 ± 11 years, of whom 83 (64%) were male and 97 (75%) had ≥ 3 risk factors for CAD. They underwent exercise SE. The diagnostic performance of SE was analyzed to identify true positive (TP) SE results; reference methods were invasive or noninvasive coronary angiography. TP SE was the target outcome in favor of SE as the initial test. All patients were clustered into phenogroups based on differences in serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and atherogenic index (AI). TC, non-HDL-C, and AI were used to determine thresholds for belonging to a phenogroup in which the odds of TP SE were higher.

Results. The rate of TP SE was 8%. Patients with TP SE had higher levels of non-HDL-C (p = 0.001) and AI (p = 0.066) compared to the remaining patients. After clustering, 2 phenogroups were identified in the total study population, uniting the 36% of patients with the highest non-HDL-C and AI. The odds ratio for TP SE in this joint group was 7.2 (1.4–36.6). Non-LDL >4.42 mmol/l estimate joint group membership with sensitivity 0.91, specificity 0.88, and area under curve 0.97.

Conclusion. Non-HDL-C >4.42 mmol/l may be considered in low to intermediate risk acute chest pain patients with previously unverified CAD as a criterion for using SE as a starting test.

114-122 9
Abstract

Hypertrophic cardiomyopathy (HCM) is a genetically determined myocardial disease with a characteristic relentless progression. The manifestation of this pathology in childhood is associated with a high risk of sudden cardiac death and the development of heart failure (HF) symptoms. Transaortic extended septal myectomy (TAESM) is currently recognized as the “gold standard” for the treatment of this pathology. However, data on the outcomes of such interventions in children with obstructive HCM are very limited, which does not allow for a complete assessment of its effectiveness.

Aim: To evaluate structural and systolic-diastolic changes in the characteristics of the left heart chambers in children with obstructive HCM after TAESM in the early and long-term follow-up periods, based on echocardiography (EchoCG) data.

Material and Methods. A retrospective analysis was conducted of data from children with HCM after successful TAESM in the cardiac surgery department No. 2 of the Research Institute of Cardiology, Tomsk National Research Medical Center, from 2010 to 2024. Immediate and long-term EchoCG indicators of heart structures were evaluated.

Results. The average age of patients was 5.51 ± 2.2 years. 46 (92%) patients had symptoms of HF. Biventricular myectomy was performed in 16 (32%) cases. In the preoperative period, there was a significant gradient in the left ventricular outflow tract (LVOT) of 75.0 [57.0; 127.0] mm Hg, mitral regurgitation of varying degrees, and systolic anterior motion of the mitral valve (SAM syndrome) in all patients. After successful TAESM, a significant decrease in dynamic LVOT obstruction, structural and anatomical characteristics, and systolic and diastolic function of the left ventricle (LV) was recorded. Follow-up in the long-term period showed a decrease in the median z-score of the left ventricular posterior wall thickness from 2.6 [0.9; 5.2] to 2.0 [1.1; 3.12], the left ventricular mass index from 167.6 [55.1; 370.37] to 148.66 [34.25; 3259.1] g/m2, the TEI index from 0.95 [0.3; 1.64] to 0.65 [0.34; 1.15], p = 0.04; 0.012 and 0.024, respectively. The z-score of the left ventricular end-diastolic volume (EDV) also changed statistically significantly from –3.8 [–2.42; 5.99] to –0.07 [–1.99; 5.6], p = 0.034. The remaining indicators remained within the reference values.

Conclusion: TAESM is an effective procedure for reducing the gradient in the LVOT, eliminating SAM syndrome, and reducing mitral regurgitation in children with obstructive HCM, both in the early and long-term follow-up periods. These results are confirmed by EchoCG data, the “gold standard” of diagnosis. In addition, there is a significant decrease in left ventricular myocardial mass, the z-score of the LV posterior wall thickness, and the left atrial volume index, which may indirectly indicate reverse remodeling of the chambers after successful TAESM in children. A statistically significant decrease in the z-score of hypertrophic and restrictive cardiomyopathy after TRESM indicates the possibility of using these indicators to quantitatively assess the effectiveness of surgical intervention.

123-130 52
Abstract

Introduction. The relevance of this work is due to the high incidence of pacemaker-induced cardiomyopathy (PICM) associated with chronic right ventricular pacing, reaching up to 30% in the pediatric population. Current evidence suggests the benefits of left ventricular (LV) pacing in preserving contractile function and intraventricular synchrony. This study presents the immediate and longterm results of epicardial LV pacemaker lead implantation in children.

Aim: To retrospectively assess epicardial LV pacing in children with atrioventricular blocks (AVB).

Material and methods. This single-center retrospective study included patients with clinically significant atrioventricular (AV) block who underwent implantation of an epicardial pacing system with the ventricular lead localized in the LV apex. In the early and late postoperative periods, all patients underwent a comprehensive examination, including: 12-channel electrocardiography (ECG) with assessment of the QRS complex width, pacemaker function control, 24-hour Holter monitoring, echocardiography (EchoCG) according to a standard protocol with determination of LV contractile function parameters, chest X-ray in the frontal and lateral views. To minimize the influence of anthropometric variability in childhood, such EchoCG parameters as LV end-diastolic volume, as well as the sizes of the left and right atria were expressed as a percentage of the expected values, taking into account weight and height characteristics. Additionally, intraventricular dyssynchrony (IVD) was assessed using tissue Doppler ultrasonography and global longitudinal strain (GLS) of the LV using Speckle-tracking echocardiography.

Results. From 2013 to 2024, 36 patients underwent primary implantation of an epicardial pacemaker system with the ventricular lead localized at the apex of the LV (33 dual-chamber systems in DDD mode, 3 single-chamber systems in VVI mode). The age of patients at the time of surgery was 4 [1;7] years, from 14 days to 14 years. There were no clinical signs of heart failure and echocardiographic markers of PICMP in the entire group in the early postoperative period and during long-term follow-up (up to 9 years). During longterm follow-up (up to 9 years), all patients had no clinical signs of heart failure and echocardiographic markers of PICMP, including IVD and increased LV GLS.

Conclusion. Epicardial LV pacing in children with AVB demonstrates favorable long-term results, including preservation of systolic function, intraventricular synchrony, and absence of signs of PICMP. The data obtained confirm the advisability of choosing the LV apex as the optimal implantation point in this category of patients.

131-139 9
Abstract

Introduction. The COVID-19 pandemic caused an increase in the number of patients with persistent pulmonary changes, characterized by long-term retention of areas of pulmonary consolidation. While standard computed tomography (CT) remains the primary diagnostic method, it has limited capability in differentiating between benign and malignant processes due to the nonspecific nature of their radiological features. Recently, with the advancement of new technologies in radiological imaging, it becomes possible to evaluate regional blood flow in various organs and tissues through specialized perfusion studies using CT and magnetic resonance imaging (MRI).

Aim: To assess the diagnostic significance of quantitative parameters of perfusion computed tomography, such as blood flow (BF), blood volume (BV), vascular permeability (PS), mean transit time (MTT), and time to peak (TTP), in differentiating post-inflammatory and malignant areas of pulmonary consolidation in patients recovered from COVID-19-associated pneumonia.

The retrospective cohort study included a group of patients (n = 41) aged 18 to 75 years with a history of COVID-19-associated pneumonia confirmed by positive PCR test results, with persistent clinical manifestations of post-COVID syndrome 12 weeks after discharge from the hospital. At the stage of in-depth clinical examination, all patients underwent CT of the chest organs, which revealed areas of lung parenchyma consolidation larger than 1 cm in size, which could not be unambiguously differentiated between post-inflammatory and neoplastic changes according to native and contrast CT. Perfusion CT was performed using a low-dose protocol (100 kV, 200 mA) on a 128-slice GE Optima CT660 computed tomography scanner with intravenous administration of 50–60 ml of iodine-containing contrast at an injection rate of 4.0 ml/s. The slice thickness was 5 mm with a scanning duration of 45–50 s. Material and Methods. The retrospective cohort study included a group of patients (n = 41) aged 18 to 75 years with a history of COVID-19-associated pneumonia confirmed by positive PCR test results, who exhibited persistent clinical manifestations of postCOVID syndrome 12 weeks after hospital discharge. These patients underwent perfusion CT as a part of an in-depth clinical follow-up. All patients received a chest CT scan, which revealed areas of pulmonary parenchymal consolidation larger than 1 cm that could not be definitively differentiated between post-inflammatory and neoplastic changes based on native and contrast-enhanced CT findings. Perfusion CT was performed using a low-dose protocol (100 kV, 200 mA) on a 128-slice GE Optima CT 660 scanner with intravenous administration of an iodinated contrast agent (50–60 mL) at an injection rate of 4.0 mL/s. The slice thickness was 5 mm, and the scan duration was 45–50 seconds.

Results. Statistically significant differences were found in vascular wall permeability and time to peak contrast enhancement between neoplastic and post-inflammatory consolidation areas: PS was 13.54 (5.71; 66.01) mL/100 g/min and TTP was 11.57 (7.19; 15.71) seconds for neoplastic lesions, compared to 5.30 (1.90; 10.63) mL/100 g/min and 32.55 (15.83; 38.28) seconds, respectively, for post-inflammatory lesions. Logistic regression analysis confirmed the high diagnostic efficacy of the model incorporating PS and TTP: the area under the ROC curve (AUC) was 87.5%, sensitivity was 80%, and specificity was 81.3%. TTP demonstrated the greatest contribution to differentiating the lesions: p = 0.004; OR = 0.888; 95% CI OR (0.81989; 0.96254), while PS showed moderate significance: p = 0.075; OR = 1.057; 95% CI OR (0.99445; 1.12421).

Conclusion. Quantitative parameters of vascular permeability and time to peak contrast enhancement have significant, statistically reliable diagnostic value compared to other parameters such as blood flow rate, blood volume, and mean transit time of the contrast agent. These parameters can serve for the differential assessment of pulmonary consolidation characteristics.

140-147 9
Abstract

Aim: To analyze the results of antegrade brain perfusion via the brachiocephalic trunk during hemiarch surgery in patients with variant anatomy of the brachiocephalic trunk.

Material and Methods. The retrospective study included 259 patients who underwent surgery for an ascending aneurysm. The patients were divided into two groups depending on the anatomy of the brachiocephalic trunk: with normal (n = 202) and variant vascular anatomy (n = 57). Intraoperative and early postoperative data were analyzed in patients of both groups, including an assessment of neurological and cognitive status.

Results. According to infrared spectroscopy, the level of brain oxygenation in patients of both groups did not exceed normal values during the entire operation, including the period of circulatory arrest (63–72%). In 1 (0.49%) case, a stroke developed in the group with normal brachiocephalic trunk anatomy. The incidence of delirious condition in the early postoperative period was higher in the group with normal brachiocephalic trunk anatomy – 8 (3.9%) versus 1 (1.7%) cases in the group with variant brachiocephalic trunk anatomy, but without statistically significant differences (p = 0.414). Cognitive function in the postoperative period in patients in the groups with normal and variant brachiocephalic trunk anatomy did not decrease below the normal threshold of 25 and 23 points, respectively (p = 0.11).

Conclusions. Antegrade perfusion of the brain through the brachiocephalic trunk during hemiarch operations in patients with normal and variant anatomy of the brachiocephalic trunk does not worsen cognitive status, reduces the frequency of neurological complications, thus this type of perfusion is appropriate, safe and effective.

148-160 93
Abstract

Background. Aortic dissection remains one of the most challenging cardiovascular pathologies for radical surgical treatment. The frozen elephant trunk (FET) procedure allows simultaneous reconstruction of the aortic arch and descending thoracic aorta. However, long-term outcomes are largely determined by postoperative aortic remodeling.

Aim: To compare aortic remodeling after implantation of dissection-specific versus conventional hybrid prostheses using a standardized protocol and to assess the incidence of specific complications – distal stent graft-induced new entry (dSINE) and endoleaks.

Material and Methods. This prospective single-center study included 106 patients with aortic dissection who underwent FET between 2014 and 2025. Patients were divided into two groups: Group 1 (n = 56) – “Soft Elephant Trunk” hybrid prosthesis (MedInzh, Russia); Group 2 (n = 50) – conventional hybrid prostheses (E-Vita Open Plus, Thoraflex Hybrid, Medtronic Valiant). Remodeling was assessed according to a patented protocol (RU 2841599 C1), including planimetry (area, perimeter) at 7 aortic levels and volumetry in 3 segments using CT before surgery, postoperatively, at 6 months, and annually up to 5 years. Remodeling was classified according to Dohle DS criteria as positive (PR), negative (NR), or stable (SR).

Results. At critical stent graft implantation levels (2–4), Group 1 showed a consistent decrease in NR and an increase in PR, whereas Group 2 demonstrated an irregular pattern with frequent NR episodes. Volumetric assessment revealed stable remodeling in Group 1, while Group 2 showed NR progression at 4–5 years. The 5-year incidence of dSINE was significantly lower in Group 1 (8.9% vs. 42.9%; p = 0.001). Use of a dissection-specific hybrid prosthesis was associated with a reduced risk of dSINE (OR 0.10; 95% CI 0.02–0.36; p = 0.001), while type B dissection increased the risk (OR 10.46; 95% CI 2.37–62.68; p = 0.004). Late (>5 years) type 1b endoleaks occurred more frequently in Group 2 (31.4% vs. 7.1%; p = 0.009).

Conclusions. The use of dissection-specific hybrid prostheses in aortic dissection surgery provides more stable positive remodeling and reduces the incidence of dSINE and late endoleaks compared with conventional prostheses. The standardized planimetric and volumetric protocol allows reliable monitoring of remodeling and timely identification of indications for reintervention.

161-169 15
Abstract

Introduction. Aortic valve replacement (AVR) is one of the most frequently performed procedures in cardiac surgery, which significantly improves the quality of life and increases its duration. Recently, transcatheter aortic valve implantation (TAVI) has been actively used, which is especially important in patients with concomitant pathology, in particular coronary heart disease (CHD). In this article, we describe the experience of successful surgical treatment of patients who underwent TAVI in combination with coronary artery bypass grafting.

Aim: To compare the results of open transaortic implantation of the “MedLAB–CT” prosthesis in combination with coronary bypass surgery, in comparison with similar indicators when replacing the aortic valve with a mechanical prosthesis with coronary artery bypass grafting, at the hospital stage.

Material and Methods. Patients operated in the clinic from June 2020 to November 2023. A retrospective observational comparison of the results of surgical treatment of two groups of patients was performed: Group 1 study group, which consisted of 60 patients who underwent open transaortic implantation of the prosthesis “MedLAB-CT” in combination with CABG. Group 2 control group, it included 99 patients who underwent AVR with a mechanical prosthesis and CABG. Using the Propensity Score Matching (PSM) pseudorandomization method, 60 patients were selected from the comparison group.

Results. Cardiopulmonary bypass time was significantly less in the “MedLAB-CT” + CABG group – 57.4 ± 8.3 min (p = 0.003). A statistical difference in the time of aortic clamping was revealed: in the study group had a value of 43.2 ± 5.2 min, in the comparison group 75.4 ± 9.2 min (p = 0.002). There were no statistically significant differences in the duration of surgery (p = 0.224), length of stay in the intensive care unit (p = 0.805) and hospitalization (p = 0.783).

Conclusion. The proposed method of open transaortic implantation of the MedLAB-CT prosthesis in combination with coronary bypass surgery can significantly reduce the time of cardiopulmonary bypass and myocardial ischemia, which has a positive effect on the course of the postoperative period.

170-177 9
Abstract

Introduction. Chronic bronchitis is the most common chronic lung disease. The main problem of this disease is late diagnosis due to mild clinical symptomatology and untimely application of patients for medical help. One tool to solve this problem is the search of predictors of bronchiectasis development in patients with chronic mucopurulent bronchitis.

Aim: To optimize the prediction of bronchiectasis formation in patients with chronic mucopurulent bronchitis.

Material and Methods. Observation of 92 patients with chronic mucopurulent bronchitis was carried out and an attempt to predict bronchiectasis formation in them after 12 months of observation was made. The course of chronic mucopurulent bronchitis was assessed after 12 months. The main group was divided into two subgroups depending on the development of bronchiectasis according to chest computed tomography (CCT). The content of circulating annexin V mononuclear cells at different stages of apoptosis of circulating annexin V mononuclear cells and the neutrophil-lymphocyte index (NLI) were determined.

Results. To develop a personalized prediction of the probability of bronchiectasis formation in patients with chronic mucopurulent bronchitis after 12 months, the studied biomarkers were analyzed and the dynamics of these biomarkers were assessed after 12 months of observation (second control point). Increasing the probability of bronchiectasis development in patients with chronic mucous-purulent bronchitis according to the results of the study are: increase in the value of neutrophil-lymphocytic index at exacerbation of chronic mucous-purulent bronchitis by 1 increases the risk of bronchiectasis formation in 57,136. The presence of association of microbial agents increases the risk of bronchiectasis formation by 57,077 times. Increase in the specific weight (%) of circulating annexin V mononuclear cells at the early stage of apoptosis at the beginning of exacerbation by 1% increases the risk of bronchiectasis formation by 4,982 times, increase in disease duration by 1 year increases the risk by 1,633 times.

Conclusion. The obtained personalized algorithm for predicting the probability of bronchiectasis formation in patients with chronic mucopurulent bronchitis has high sensitivity and specificity – 96,6% and 98,4%, respectively.

EXPERIMENTAL STUDIES

178-187 10
Abstract

Cardiac surgeries with cardiopulmonary bypass (CBP) lead to significant changes in the morphofunctional state of the lungs, accompanied by the formation of post-perfusion pulmonary syndrome. Reperfusion significantly increases lung damage due to the influx of oxygen and calcium ions, as well as leukocytes and blood clotting system components activated by contact with the apparatus circuit material. Cells of the inflammatory infiltrate damage matrix proteins by releasing proteolytic enzymes that damage the structure of collagen and elastin and lead to the formation of their modified forms with altered spatial organization and mechanical properties. Nitric oxide (II) (NO) has the potential to affect the key pathogenic mechanisms of ischemic-reperfusion damage. Under cardiopulmonary bypass, there is a deficiency of endogenous nitric oxide, so perioperative delivery of exogenous NO is likely to compensate for this deficiency.

Aim: To characterize the changes occurring in the intercellular matrix of the lungs under the conditions of simulated surgeries with cardiopulmonary bypass and the effect of perioperative delivery of nitric oxide on their severity.

Material and Methods. The study was conducted on 6 male domestic sheep. The animals of the “CBP” group (n = 3) underwent CBP and mechanical ventilation (MV) according to the standard procedure. In the “CBP + NO” group (n = 3), sheep additionally received nitric oxide (II) at a dose of 80 ppm through modified circuits of ventilators and cardiopulmonary bypass throughout the experiment. The duration of cardiopulmonary bypass was 90 minutes. The content of matrix metalloproteinases-2 and -9 in the lungs was assessed by immunohistochemistry. Collagen fibers were detected by Van – Gieson staining and an immunohistochemical reaction to type I collagen.

Results. In the lungs of sheep treated with nitric oxide on the background of cardiopulmonary bypass, a decrease in the intensity of immune staining for MMP-2 (p < 0.001) and MMP-9 (p < 0.001), higher specific volume (p < 0.001) and qualitative characteristics of collagen fibers were noted.

Conclusion. The use of nitric oxide in experimental modeling of cardiac surgery helps to limit the damaging effect of cardiopulmonary bypass on the intercellular matrix of the lungs.

CLINICAL CASES

188-193 9
Abstract

Patients with neoplasms have a higher risk of developing cardiovascular diseases. In 90% of patients, acute coronary catastrophe occurs with the progression of cancer. The complexity of managing such patients is associated with an increased risk of bleeding, thrombotic complications and the need for surgical treatment of cancer in the near future. We analyze a case of simultaneous stenting of the trunk of the left coronary artery and resection of the bladder for decaying adenocarcinoma in a patient with acute coronary syndrome without high-risk ST segment elevation. The main principle of managing such patients today remains the joint work of a multidisciplinary team and an individual approach.

HEALTHCARE AND PUBLIC HEALTH

194-204 12
Abstract

One of the key tasks of the development of the healthcare system is to create conditions for increasing the availability of medical care to the population, a problem which is most acutely felt in small and hard-to-reach settlements. The purpose of this review is to analyze and summarize the available world data on organizational technologies for the provision of medical care in small and hard-to-reach settlements. During the work, a literature review of scientific original articles included in international and domestic databases was conducted using PRISMA criteria. The main research question was formed as follows: what organizational technologies are used in healthcare to increase the availability of medical care in small and hard-to-reach settlements?

The literature review demonstrates that currently various organizational tools and technologies are used in the world that reliably contribute to eliminating inequalities in the receipt of medical services, as well as improving clinical outcomes, despite transport barriers. At the same time, significant opportunities for modern medical and organizational solutions have been established both in the prevention of diseases and in diagnosis, treatment and rehabilitation. A systematic review revealed the limitations of applied research demonstrating the implementation of comprehensive organizational models with performance evaluation before and after the intervention, which forms a reserve and opportunity for further research in the field.

205-211 7
Abstract

Introduction. Due to the increasing number of cancer patients, it is necessary to improve the quality of specialized medical care that is offered to them. Radiation therapy has been one of the most significant and rapidly developing methods of treating malignant neoplasms for several decades. The equipment, technologies, and organization of radiation therapy in specialized medical institutions are constantly being improved. However, since the beginning of 2024, there has been a critical situation in the radiation therapy departments of the Primorsky Regional Cancer Center, which is caused by the long waiting lists for patients who are referred for radiation therapy in a 24-hour hospital. An analysis of the delay in hospitalization for radiation therapy has identified the need to optimize the existing system for organizing pre-radiation preparation.

Aim: To study the organizational and clinical-economic effectiveness of implementing of pre-hospital pre-radiation topometric training in the activities of an oncological dispensary.

Material and Methods. The study used statistical data and regulations governing the provision of medical care in the field of “oncology”, applied the method of clinical and economic research “impact on the budget”, general scientific methods – systematization and comparison.

Results. The scientific substantiation of the clinical and economic efficiency of the organization of pre-radiation topometric training at the pre-hospital stage is presented. The possibility of carrying out at least 220 additional hospitalizations per year to provide highly effective medical care to patients with oncological diseases without additional financial costs for increasing the bed capacity has been proven. The financial equivalent of the achieved benefits has been calculated, amounting to more than 3 million 280 thousand rubles per year.

Conclusion. The introduction of pre-hospital pre-radiation training significantly improves the quality of specialized medical care for patients with cancer, is clinically effective and economically justified. The most valuable aspect of the organizational improvement being studied is the absence of the need to increase financial investments in the activities of a medical organization. The benefits obtained can be further increased by changing the order of topometry processes and inpatient patient card design for the category of patients who have not completed pre-radiation training at the pre-hospital stage.

DIGITAL TECHNOLOGIES IN MEDICINE AND HEALTHCARE

212-224 11
Abstract

Introduction. The high prevalence of chest X-ray and fluorographic examinations creates significant workload for the radiology department. One promising solution for optimizing the preventive radiography and fluorography pipelines is employing artificial intelligence (AI) technologies. This approach demonstrates effectiveness in triaging studies based on binary assessment (“normal”/”abnormal”). Evaluation of this method identified shortcomings in the form of false-negative results requiring further study and improvement.

Aim: To evaluate potential methods for reducing false-negative results in automated triage of preventive chest radiographic examinations using AI-powered software.

Material and Methods. In a retrospective diagnostic study conducted from May 1, 2025, to June 30, 2025, we analyzed 411 cases of false-negative results identified during evaluation of automated triage powered by three different AI models. The study utilized data from preventive chest radiographic examinations performed in outpatient setting and mass screening examinations of the adult population in Moscow. Images were re-analyzed by two expert radiologists (> 10 years of experience) considering the available clinical information and patient history data. Analytical and descriptive statistical methods were used.

Results. The majority (n = 266) of false-negative results were associated with missed infiltrative changes and pulmonary foci. The remaining clinically significant discrepancies were observed in 24 cases.

Analysis of archival data and patient histories identified additional information that, when integrated into AI-powered services, could influence study interpretation and reduce false-negative risk. Such data were found in 68.3% of cases (n = 198) with clinically significant omissions and in 5% (n = 6) with clinically insignificant omissions.

Conclusion. Reducing false-negative results requires an integrated approach: implementing duplicate AI services, improving physician referral quality, and integrating clinical data and previous patient study results into AI algorithms, necessitating development of multimodal AI software.

225-234 9
Abstract

Aim: To validate an automated design algorithm for the leaflet apparatus of a polymeric heart valve prosthesis, focusing on achieving high hydrodynamic performance through design, prototyping, and in vitro testing.

Material and Methods. The study employs a proprietary automated design algorithm based on computational modeling and numerical analysis of the hydrodynamic characteristics of heart valve prosthesis leaflets in computational modeling. The algorithm generated a large number of geometrical variants (over 16,000), which were subsequently evaluated for their functionality, including the effective orifice area, coaptation area, and stress distribution within the leaflet material. Based on the design algorithm's output, the optimal leaflet geometry was selected and prototyped using casting techniques to produce three samples. These prototypes were evaluated in vitro under simulated physiological flow conditions using a hydrodynamic testing system.

Results. The geometries produced by the design algorithm exhibited a wide range of quantitative metrics for the targets: the mean effective orifice area was 38.85% (minimum 7.54%; maximum 85.78%); the coaptation area was 1.08% (0–1.88%); and the maximum stress was 0.47 MPa (0.25–1.43 MPa). The optimal leaflet geometry selected for prototyping demonstrated an effective orifice area of 85.75%, a coaptation area of 0.45%, and a maximum stress of 1.023 MPa. Prototyping and subsequent in vitro testing confirmed the high functional performance of the developed sample, although significant deviations in quantitative indicators from the results of numerical modeling were observed due to the specifics of prototyping. These discrepancies indicate the need for further refinement of the algorithm and improvements in the prototyping methodology.

Conclusion. The study confirms the effectiveness of the proposed automated algorithm for the development and optimization of polymeric heart valve prostheses. The primary advantage of this methodology lies in its ability to rapidly generate and evaluate a large number of geometrical variants, thereby enhancing the accuracy and functionality of the final product. The results demonstrate the significant potential of automated design in biomedical engineering and pave the way for the development of more advanced medical devices. Future efforts should focus on improving the accuracy of numerical models and prototyping techniques to ensure even higher quality and durability of polymeric heart valve prostheses.



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ISSN 2713-2927 (Print)
ISSN 2713-265X (Online)