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Complex Issues of Cardiovascular Diseases

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Vol 11, No 3 (2022)
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ORIGINAL STUDIES. Cardiology

8-16 365
Abstract

Highlights. Early atherosclerotic changes in the abdominal aortic wall and common iliac arteries in patients without clinical manifestations of critical atherosclerotic stenosis of the lower extremity arteries were studied using contrast enhanced magnetic resonance imaging. A method for quantitative characterization of the accumulation of paramagnetic contrast in the abdominal aortic wall and common iliac arteries is presented.

Aim. To study the pattern of early atherosclerotic lesions of the abdominal aortic wall and common iliac arteries in patients without clinical manifestations of critical atherosclerotic stenosis of the lower extremity arteries using paramagnetic contrast enhancement (CE-) MRI.

Methods. The retrospective study included 36 patients (25 men, 11 women) who underwent MRI of the lumbar spine with CE, without signs of atherosclerosis of the lower extremities. Subsequently, 2.5 and 4 years after CE-MRI, two patients developed acute leg ischemia and required vascular surgeries. At the time of the study, both had higher levels of C-reactive protein in the blood (6.3 mg/L and 5.9 mg/L, while the other patients had <4.2 mg/L). MRI included T2 – and T1-weighted spin-echo scans (T2-w and T1-w) in the axial and sagittal planes, before and in 10-15 minutes after contrast injection. The index of enhancement (IE) of T1-w was calculated based on the ratio of mean intensities of the region of arterial wall over aorta and iliac arteries in CE-MRI and pre-contrast MRI: IE = Int.T1–w. CE / Int. T1–w pre-contrast.

Results. Depending on the IE of the abdominal aortic wall in CE-MRI, patients were divided into three groups: group 1 (n = 11) with IE ≤1.05; group 2 (n = 16) with 1.05 <IE ≤1.15; group 3 (n = 9) with IE >1.15. The aortic IE in all three groups was 1,03 (1,01;1,03); 1,10 (1,09;1,15); 1,36 (1,16;1,40) respectively (p<0.001). The thickness of the abdominal aortic wall progressively increased moving up the group 1, while statistically significant differences were found only between the groups 1 and 3, and the groups 2 and 3 (p<0.001). There were no differences in the wall thickness of the common iliac arteries and the diameter of all vessels studied between the groups. Two patients from the group 3 later presented with acute limb ischemia.

Conclusion. The state of the abdominal aortic wall and common iliac arteries should be evaluated, and IE of T1-w should be calculated when performing CE-MRI examination of the area of the descending aorta to assess pathological neoangiogenesis as the most important component of atherogenesis.

17-28 480
Abstract

 

Highlights. CYP2C19 gene polymorphisms in patients with acute myocardial infarction are common in clinical practice. The article assesses the role of genetic predisposition in the development of ischemic and hemorrhagic events during dual antiplatelet therapy (aspirin and clopidogrel) within the first 12 months after revascularization for acute myocardial infarction.

Aim. To evaluate the impact of CYP2C19 gene *1, *2, *3, *17 alleles polymorphism on 12-month clinical outcomes in patients who underwent coronary revascularization due to acute myocardial infarction and took clopidogrel.

Methods. 363 patients with acute myocardial infarction undergoing percutaneous coronary intervention were enrolled in the prospectively study in 2010–2012. CYP2C19 gene *1, *2, *3, *17 alleles polymorphism analysis was performed in all study participants. Dual antiplatelet therapy, consisting of aspirin and clopidogrel, was prescribed for 12 months. The follow-up period was 12 months, the incidence   of cardiovascular death, non-fatal myocardial infarction, stroke and bleeding was assessed.

Results. 12 months after inclusion in the study, the incidence of composite endpoint (defined as cardiovascular death, non-fatal myocardial infarction and stroke) was observed in 18 patients (7% [5%; 11%]; 95% CI) with wild-type CYP2C19 gene and in 12 patients (11% [6%; 18%]; 95% CI) with lost-of-function *2+*3 alleles, with no statistical difference (OR = 1.6 [0.7; 3.6], 95% CI; p = 0.301). Presence of any LOF-alleles did not predict composite endpoint events (OR = 1.56 [0.71; 3.34], 95% CI, p<0.253). Multivariable logistic regression analysis revealed that CYP2C19*2 homozygotes have higher risk of composite endpoint (OR = 6.34, 95% CI [1.57; 22.23], p<0.005) and myocardial infarction (OR = 5.45, 95% CI [1.14; 19.97], p<0.016) compared to *2 heterozygotes and wild-type carriers.    14 patients had major bleedings, required blood transfusion or hospitalization. Patient’s age, increase in creatinine level and gain-of-function (GOF) CYP2C19*17 homozygotic carriage were identified as the predictors of major bleeding during follow-up period.

Conclusion. In this study CYP2C19 LOF alleles polymorphism except the CYP2C19*2 homozygotic carriage demonstrated no impact on the incidence of ischemic events during 12-month follow-up in patients with acute MI who underwent successful revascularization. CYP2C19*17 homozygotes demonstrated increased risk of major bleeding only in young individuals with elevated blood creatinine levels.

29-39 354
Abstract

Highlights. The most important goal of atrial fibrillation surgical treatment is to eliminate the arrhythmia in order to restore atrial contractility and improve their transport function. Our study showed positive dynamics of atrial contractility and remodeling after the maze-3 procedure against the background of a regular heart rhythm restoration. The study of sinus rhythm predictors maintenance and recovery of atrial transport function will help to make patient selection more personified.

Aim. Evaluation of atrial contractility and remodeling after the maze-3 procedure with combined interventions on the heart.

Methods. The analysis of 217 combined surgical interventions was carried out, where a maze-3 was used to treat atrial fibrillation (AF). The operations were performed in our center from 2012 to 2016. Key points of the study: rhythm after surgery and echocardiographic control in the long-term follow-up in order to determine the dynamics of atrial contractility and volumes. The average follow-up period was 47 (1–100) months. 40 (18.4%) patients had paroxysmal, 38 (17.5%) persistent, 139 (64.1%) long-term persistent AF. The mean AF duration before surgery was 27.4 months (1–200 months). The indications for the maze-3 procedure were: ineffectiveness of antiarrhythmic therapy, the need to perform combined cardiac procedures. We used standard statistical research methods with one – and multivariate logistic regression.

Results. In the long-term follow-up, sinus rhythm (SR) persists in 79% of patients. In the long-term follow-up, in this group of patients, the left atrial contractility was  restored  from  76%  to  91%,  while  the  biatrial  contractility  increased from 82 to 96%. Shorter AF duration before surgery was a positive predictor of SR recovery and atrial contractility (p = 0.005), while pulmonary artery pressure and patient age negatively affected these indicators (p = 0.041 and p = 0.038, respectively). The presence of SR early after surgery was not a significant predictor of AF freedom. At the same time, according to the long-term observations, patients maintaining a regular atrial heart rate had positive indicators of atrial systolic function restoration and a positive dynamics of a decrease in atrial volumes.

Conclusion. SR and restoration of left atrial contractility are two interrelated goals of the maze procedure. The negative factors associated with the failure of surgical treatment of AF are increased pressure in the pulmonary artery, long-term AF before surgery, and the age of patients.

40-50 361
Abstract

Highlights. The frequency of long-term fatal cardiovascular complications in patients with chronic coronary syndrome subjected to selective (non-emergency) percutaneous coronary interventions was estimated.

Risk stratification model of long-term fatal cardiovascular complications in patients with chronic coronary syndrome subjected to selective percutaneous coronary interventions has been created.

Aim. To determine the frequency of long-term fatal cardiovascular events (CVE) after elective percutaneous coronary interventions (PCI) and to develop a model for stratifying the risk of these events.

Methods. 150 patients with chronic coronary syndrome and indications for endovascular myocardial  revascularization  were  included  in  the  research.  After  PCI  the patients were observed on an outpatient basis for year. The frequency of fatal cardiovascular complications was estimated by telephone interview 6 years after the index intervention.

Results. Survival in the study group after 6 years was 86.1%. Fatal CVEs were reported in 10.6% of patients. The following baseline variables were significant predictors of cardiovascular death included in the individual risk assessment model: NYHA functional class of chronic heart failure (odds ratio (OR) 0.06, 95% confidence interval (CI) 0.003-1.106), lean plasma glucose level (OR 0.07, 95% CI 0.12-0.43), atrial fibrillation (OR 43.1, 95% CI 2.01–922.01), as well as the value of creatinine in the blood one year after the intervention (OR 1.14, 95% CI 1.0–1.3) and glomerular filtration rate (CKD-EPI) (OR 1.4, 95% CI 1.09–1.81). The area under the curve (AUC) of the developed model was 0.976 [95% CI 0,000–1,000].

Conclusion. The proposed risk stratification model of developing long-term fatal cardiovascular complications in patients with chronic coronary syndrome subjected to selective (non-emergency) PCI allows identifying patients with an unfavorable long-term (six-year) prognosis.

51-63 456
Abstract

Highlights. Taking into account the connection between the increase in the volume of myocardial adipose tissue and vessels with massive calcification of the coronary arteries in coronary heart disease, morphometry of epicardial and perivascular adipose tissue during routine tomographic examinations can be considered as a non-invasive technique for determining a surrogate marker of severe coronary lesion.

Aim. To evaluate the relationship of coronary artery calcification (CA) and morphometric parameters of local fat depots in patients with coronary heart disease (CHD).

Methods. 125 patients with stable coronary artery disease aged 59±8.9 years were examined. Visualization of local fat depots, abdominal fat depots, and coronary calcification (CC) was performed using multislice computed tomography with subsequent post-processing of images on the Siemens Leonardo workstation (Germany). Non-contrast magnetic resonance imaging of the heart was used to determine the EAT thickness.

Results. Coronary calcification was detected in 95.2% of the examined patients with coronary artery disease (n = 119). There were higher indices of the EAT thickness of the right and left ventricles in case of massive CC, the thickness of the pericardial adipose tissue at the level of the trunk of the left coronary, anterior descending, circumflex arteries, and increased morphometry indices of the abdominal fat depot in comparison with the patients who had moderate and medium CC.

Conclusion. An increase in the volume of adipose tissue of the myocardium and vessels in CAD is associated with massive calcification, which is reflected in the pathogenetic “adipovascular” continuum, characterized by the stimulation of adipogenesis against the background of atherocalcinosis of the coronary arteries. Morphometry of epicardial and perivascular adipose tissue during routine tomographic studies is a non-invasive technique for determining a surrogate marker of severe coronary lesions.

64-71 2058
Abstract

Highlights. Recurrent myocardial infarction remains an important health problem due to the high mortality of patients. At the same time, there is practically no data in the literature on the prevalence of this complication in the population, which makes studies carried out on the basis of long-term epidemiological programs relevant. The analysis of the “Acute Myocardial Infarction Register” (Tomsk) presented in the paper showed not only a high mortality rate of patients with recurrent infarction, but also a tendency to increase the incidence of this complication, which confirms the need to search for predictors of its occurrence.

Aim. To determine the incidence of recurrent myocardial infarction (RMI) and mortality in patients with RMI in Tomsk for five years (2016–2020), to perform a clinical and anamnestic analysis of RMI episodes registered in 2019 and 2020.

Methods. The study was performed on the basis of the data from the information and analytical database of the WHO program “Registry of Acute Myocardial Infarction”. In 2019–2020 1748 cases of acute myocardial infarction (AMI) were registered, in 1078 men (61.7%) and 670 women (38.3%). 87 patients with RMI were identified, which accounted for 5%. In this group, there were 46 men (52.9%) and 41 (47.1%) women. The age of RMI patients was almost identical (72.2±12.7 years old in men and 72.1±11.4 years old in women).

Results. 51 (58.6%) patients were hospitalized with index AMI in a specialized department, 14 (16.1%) were treated in non-core hospitals and 22 (25.3%) people died at the prehospital stage. Patients with AMI with RMI and without RMI did not differ in clinical and anamnestic parameters. Coronary ventriculography was performed in 51 (58.6%) patients with RMI, in 41 (80.4%) cases there was a multivessel lesion of the coronary bed. RMI occurred in 43 (49.4%) patients who were treated in hospital, in 22 (25.3%) – at home, after discharge. RMI was detected in 22 (25.3%) of the dead at the prehospital stage. Typical and atypical clinical manifestations of RMI occurred in 53% and 47%, respectively. Stent thrombosis (24.1%) and the lack of treatment for indexAMI (35.6%) prevailed among the causes of RMI. It was not possible to establish the cause in 27.6% of cases. An increase in the incidence of RMI was noted from 2016 to 2020. During the follow-up, the mortality rate from RMI was two times higher than that among AMI patients in general.

Conclusion. There were no significant clinical, anamnestic and other differences among patients with and without RMI. The established causes of RMI are not so much causes as a consequence of some factors. This fact, combined with the high mortality rate from RMI and the trend towards an increase in the incidence of RMI, makes it necessary to search for predictors of the onset of RMI and ways to prevent them.

ORIGINAL STUDIES. Cardiology. Internal medicine

72-83 423
Abstract

Highlights. Elevated levels of matrix metalloproteinases 2 and 9 are associated with the initiation and severity of CHF developed after breast cancer therapy with anthracyclines, which may contribute to cardiac remodeling and the progression of systolic dysfunction. Concentrations of matrix metalloproteinases-2 and -9 in blood serum serve as predictors of the unfavorable course of anthracycline-induced heart failure.

Aim. To assess the role of matrix metalloproteinases-2 (MMP-2) and 9 (MMP-9) in the development and course of anthracycline-induced chronic heart failure (CHF) during 24 months of observation.

Methods. The study included 114 women 12 months after completion of chemotherapy (CT) for breast cancer and developed CHF. The control group (n = 70) consisted of women (mean age 45.0 [42.0; 50.0] years old) who received doxorubicin as part of chemotherapy, but they did not develop CHF 12 months after completion of chemotherapy. The levels of biomarkers (MMP-2, MMP-9, NT-proBNP) in blood serum were determined using a sandwich immunoassay.

Results. Patients with CHF had signs of cardiac remodeling and higher values of NT-proBNP, MMP-2 and MMP-9 (p<0.001) than women from the control group. After 24 months of observation, all patients with CHF were divided into 2 groups: group 1 – women with an unfavorable course of CHF (n = 54), group 2 – women with favorable course of pathology (n = 60). Criteria for the unfavorable course of CHF: the emergence of new or worsening of existing symptoms/signs of heart failure; and/or hospitalization due to HF decompensation; decrease in left ventricular ejection fraction by more than 10%; or an increase in the functional class of CHF by 1 or more. Baseline echocardiographic parameters and NT-proBNP values did not differ in groups 1 and 2. Levels of MMP-2 were higher by 8% (p = 0.017) and MMP-9 by 18.4% (p<0.001) in group 1. In 1 group the level of MMP-2 decreased after 24 months of observation. In group 2 the level of MMP-2 increased by the end of the observation period. MMP-2 levels ≥388.2 pg/ml (sensitivity 46%, specificity 80%; AUC = 0.64; p = 0.013) and MMP-9 ≥21.3 pg/ml (sensitivity 86%, specificity 84.4%; AUC = 0.9; p<0.001) were determined as predictors of an unfavorable course of CHF.

Conclusion. Remodeling of the extracellular matrix may play an important role in the pathogenesis of CHF initiated by drugs of the anthracycline class. Elevated levels of MMP-2 and MMP-9 in the blood serum are associated with an unfavorable course of anthracycline-induced CHF and can be recommended when assessing the risk of an unfavorable course of pathology.

ORIGINAL STUDIES. Pathological physiology

84-96 510
Abstract

Highlights. The features of subsets of monocytes in combination with the levels of desquamated endotheliocytes, endothelial damage and regeneration mediators and progenitor cell migration-enhancing factors in patients with coronary heart disease and with/without ischemic cardiomyopathy were analyzed. For the first time it was shown that in patients with ischemic cardiomyopathy, compared with CHD patients without cardiomyopathy, higher desquamation of the endothelium is associated with a deficiency of non-classical monocytes and reduced migration of progenitor endothelial cells (VEGFR2+-monocytes) with regenerative potential across the bone marrow due to a deficiency of the HIF-1α mediator in the blood.

Background. The development of ischemic cardiomyopathy (ICM) is an understudied process, and one of its elements may be insufficient regeneration of blood vessels due to an imbalance of subsets of monocytes in the blood.

Aim. To assess subsets of monocytes and desquamated endothelial cells in combination with endothelial damage and regeneration mediators in the blood of patients with coronary heart disease (CHD) and with/without ICM.

Methods. The study included 30 patients with ICM, 22 patients with coronary heart disease without cardiomyopathy aged 55–69 years, and 18 healthy donors. In whole blood, the populations of CD45CD146+ desquamated endothelial cells and progenitor endothelial cells related to CD14+VEGFR2+  monocytes, intermediate CD14++CD16+   and  non-classical  CD14+CD16++   monocytes  were  assessed  by flow cytometry  using  the  appropriate  monoclonal  antibodies  (BD  Biosciens, USA). In blood plasma, the levels of hypoxia-inducible factor HIF-1α, monocyte chemoattractant protein MCP-1 and matrix metalloproteinase MMP-9 were assessed by enzyme immunoassay. The results of the analysis were considered significant at p<0.05.

Results. The number of progenitor and desquamated endothelial cells was increased in both groups of patients with coronary artery disease. At the same time, in patients with ICM, the number of progenitor endothelial cells did not reach the number noted in patients with CHD without cardiomyopathy, while the number of desquamated endothelial cells reached the number noted in CHD patients without cardiomyopathy. There was a deficiency of non-classical monocytes and HIF-1α in the blood of patients with ICM, and an excess of intermediate monocytes and MCP-1 was observed in CHD patients without cardiomyopathy. The concentration of MMP-9 in patients with CHD corresponded to the norm, regardless of the presence of ICM.

Conclusion. In ICM, in contrast to CHD without cardiomyopathy, vascular damage is associated with a deficiency of nonclassical monocytes and reduced endothelial repair due to insufficient migration of progenitor endothelial cells across the bone marrow due to HIF-1α deficiency in the blood.

97-114 434
Abstract

Highlights. Spontaneous endothelial-to-mesenchymal transition of primary human umbilical vein endothelial cells (HUVEC) is characterized by an acquired expression of SNAI2 and TWIST1 genes, loss of endothelial markers and transcription factors (CD31/PECAM1, VE-cadherin, and ERG transcription factor), pronounced expression of S100A4 and ACTA2 genes, and active production of type I collagen, a major component of the extracellular matrix.

An optimal algorithm to detect endothelial-to-mesenchymal transition includes gene expression profiling of endothelial lineage markers (PECAM1, CDH5, VWF, ERG), SNAI2 and TWIST1 transcription factors, mesenchymal specification markers (FAP, S100A4, ACTA2) and markers of extracellular matrix synthesis (COL1A1, COL1A2) along with the subsequent negative staining for CD31/PECAM1, VE-cadherin, or ERG and positive staining for intracellular type I collagen.

Aim. To  develop  an  algorithm  and  tools  to  determine  endothelial-to-mesenchymal transition (EndoMT) in vitro.

Methods. We examined two batches of human umbilical vein endothelial cells (HUVEC) where the first cell batch had a conventional endothelial morphology and the second cell batch underwent a spontaneous EndoMT. Human coronary artery endothelial cells (HCAEC) and human internal thoracic artery endothelial cells (HITAEC) were used as the negative control for EndoMT. Molecular profile was assessed by means of reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining with the further confocal microscopy.

Results. In contrast to HUVEC with the physiological profile and arterial ECs, HUVEC undergoing EndoMT lost the expression of endothelial lineage markers (PECAM1, CDH5, VWF, ERG) and acquired the expression of EndoMT transcription factors (SNAI2, TWIST1), mesenchymal markers (FAP, S100A4, ACTA2), and extracellular matrix components (COL1A1, COL1A2) while retaining expression of the common vascular  markers  (HES1,  NRP1).  Western  blotting  analysis  confirmed  the loss of endothelial markers (CD31/PECAM1, VE-cadherin/CDH5, ERG) and demonstrated retained expression of abovementioned vascular markers. Negligible expression of MYH11 and SMTN genes encoding specific contractile markers (smooth muscle myosin heavy chain and smoothelin) in combination with the acquired expression of ACTA2 gene encoding less specific contractile marker alpha smooth muscle actin indicated the phenotypic identity of EndoMT-transformed HUVEC to myofibroblasts but not contractile vascular smooth muscle cells. Loss of immunofluorescence staining of endothelial markers (CD31/PECAM-1, VE-cadherin, and ERG transcription factor) and pronounced intracellular staining of type I collagen testified to the ongoing EndoMT.

Conclusion. An  algorithm  to  assess  EndoMT  implies  measurement  of  the  expression  of PECAM1, CDH5, VWF, ERG, SNAI2, TWIST1, FAP, S100A4, ACTA2, COL1A1, and COL1A2 genes in combination with the respective immunofluorescence staining for CD31/PECAM-1, VE-cadherin, or ERG transcription factor and type I collagen.

ORIGINAL STUDIES. Public health

115-124 254
Abstract

Highlights. A comparative analysis of the morbidity rate in the population in Moscow, the Central Federal District and the Russian Federation for the period from 2012 to 2019 depending on the age groups was carried out; performance of the Center for Prevention and Health Centers in Moscow and in its administrative districts was assessed; suggestions for improving the organizational structure of the population prevention in the megapolis were made.

Aim. To analyze and assess the organizational structure of population prevention in Moscow, and to suggest proposals for its improvement.

Methods. The data of the Ministry of Health of Russian Federation on the morbidity rate in the (general) population in Moscow, the Central Federal District and the Russian Federation, by age groups of the population was analyzed. The analysis and assessment of the performance was done for the following entities carrying out preventive programs in Moscow: the Center for Prevention (CP), 58 departments and 224 offices for prevention, 62 Health Centers (HC) and the performance of youth-friendly clinics in the Russian Federation. We used statistical, sociological, analytical research methods for the analysis.

Results. Total morbidity rate in the population of Moscow (2019) was lower than in the Central Federal District and in the Russian Federation, it amounted to 140,743.0 per  100  thousand  of  the  population,  in  the  Central  Federal  District  it  was 149701.0‰оо, and in the Russian Federation it was 164899.4‰оо.At the same time, total morbidity rate in children aged 14 years old in Moscow was higher than in the Russian Federation and in the Central Federal District; it amounted to 222946.1 per 100 thousand of the corresponding population, in the Russian Federation it was 219845.6‰оо, and the Central Federal District it was 211643.2‰оо. The analysis of total morbidity in children in Moscow by classes of diseases is given. The article analyzes the performance of CP and HC in Moscow and output of youth-friendly clinics in Russia. Suggestions for improving the organizational structure of the population prevention in the megapolis were made.

Conclusion. Total morbidity rate in the population in Moscow is lower than in the Central Federal District and the Russian Federation, however, the rates in children are higher than in the Russian Federation for a number of diseases. The results obtained should be taken into account in the development of the population-based prevention strategies for children. Based on the results of the study, it can be concluded that the Center and departments for prevention in Moscow are subject to reorganization; additional duties and responsibilities should be introduced and existing ones should be adjusted. It is necessary to organize the continuity and coordination in care provided by the CP, HC and primary health care physicians. It is recommended to create more youth-friendly clinics in the Russian Federation, in particular, in Moscow.

125-133 502
Abstract

Highlights. The subjective and objective indicator of health is the most important parameter characterizing the motivation of the population to preserve public health. In Russian and foreign epidemiological studies, differences in attitude to one`s health are dependent upon social and economic status, gender differences, ecology, and marital status. For the first time, the parameters of the subjective and objective indicator of health were determined among women in the population of a medium-sized urban city in Western Siberia. It must be mentioned that women remain to be the most vulnerable category of the population in terms of psychological stress. The data obtained using Tyumen`s population will assist in the prediction of the population`s response to preventive programs, estimation of the amount of preventive care needed, taking into account the expenses, and analysis of the effectiveness of possible intervention.

Aim. To determine some parameters of the subjective and objective indicator of health (health attitudes and health self-assessment) among women in urban population.

Methods. The epidemiological study included a representative sample of women of working age (25–64 years old) residing in the Central Administrative District of Tyumen, stratified by age (1 000 women, response rate 70.3%). The attitude of the population towards health was assessed using the standard WHO MONICA-psychosocial questionnaire “Awareness and Attitude towards Health”.

Results. The obtained data revealed low responsibility for health among working age women (36.5–46.7%), and predominantly negative self-assessment of health (70.0%). The results showed a low responsibility for cardiovascular health in the female population (a fifth of the population trusted only their own feelings, and more than half of the population would not seek medical help for mild pain in the chest). A trend towards increasing negative self-assessment of health and increasing trust in the examination of a physician without additional examination was noted in the participants in young to middle age range.

Conclusion. The subjective and objective indicator of population`s health requires further studies and can be used as a basis for the development and implementation of comprehensive preventive programs that take into account gender and age-dependent features and risks.

ORIGINAL STUDIES. Intensive care

134-142 328
Abstract

Highlights. The article discusses the features of general anesthesia in patients with cerebrovascular diseases using the relaxant binding agent sugammadex.

Aim. To evaluate the effectiveness of sugammadex in endovascular management of cerebrovascular diseases.

Methods. The study included 57 patients who underwent endovascular treatment of cerebrovascular disease under general anesthesia. The experimental group included 29 patients who were injected with sugammadex - a selective relaxant binding agent for reversal of neuromuscular block induced by rocuronium. The comparison group included 28 patients who did not undergo decurarization (n = 13), or it was performed with neostigmine (n = 15). Acceleromyography was used to monitor the state of neuromuscular function.

Result. Onset of action and duration of action of rocuronium at a dose of 0.9 mg/kg did not differ between the groups. The neuromuscular recovery time was 2.14 [1.67; 2.59] minutes after administration of sugammadex, compared with spontaneous 35.8 [31.5; 40.4] minutes and neostigmine-induced 22.1 [16.8; 27.3] minutes (p<0.001). No adverse or allergic reactions were noted after administration of the relaxant binding agent.

Conclusion. Using a specific antidote sugammadex to eliminate the effect of rocuronium helps to restore neuromuscular function within 2–3 minutes and assess the neurological status of patients immediately after the endovascular treatment of cerebrovascular disease.

ORIGINAL STUDIES. Cardiovascular surgery

143-151 282
Abstract

Highlights. Non-invasive method for the assessment of the mobility and deformation of the wire element of the bioprosthesis in the cardiac cycle based on the developed mathematical algorithm is presented. Numerical analysis of the behavior of the wire element of the “TiAra” bioprosthesis is shown for the first time. The developed method can be used for other medical devices as well.

Aim. To develop a method for non-invasive assessment of the mobility and deformation of the wire element of the aortic heart valve bioprosthesis in the cardiac cycle based on mathematical processing of visual medical data.

Methods. Multidetector computed tomography data of patient P. (male, 66 years old), who received the “TiAra” aortic bioprosthesis (NeoCor CJSC, Kemerovo), were used for the study. Using the built-in tools in the Mimics Medical Image Processing Software (Materialize, Belgium), based on the radio density, 5 stages of movement of  the  wire  element  of  the  bioprosthesis  were  reconstructed  in  the  form  of 3D-models.  The  differences between  the  models,  characterizing  deformation in the cardiac cycle, were quantitatively assessed using a proprietary Matlab algorithm (The MathWorks, USA), calculating the distance between similar points. Moreover, obtained data on displacements was used in the numerical study of the stress-strain state of a 3D-model of the wire element by the finite element method in the Abaqus/CAE software (Dassault Systèmes SE, France).

Results. The proposed method for assessing the mobility of the wire element made it possible to quantitatively evaluate the biomechanics of the “TiAra” stentless bioprosthesis based on multidetector computed tomography, a non-invasive clinical tool. The movements that the bioprosthesis undergoes during the cardiac cycle (the maximum value is 2.04 mm in the radial direction) are comparable to the movement of the aortic root of a healthy patient. The results of the numerical modeling of the stress state of the wire element did not indicate high amplitudes (peak value – 564 MPa) that would be capable of causing critical damage to the wire. It allows us to confirm the clinical safety of the bioprosthesis in real conditions like asymmetric and uneven loads. Moreover, deformations observed in the bioprosthesis are similar in the amplitude to the displacements of the aortic root described in the literature, which highlights the main feature of the bioprosthesis – ensuring the physiological biomechanics throughout the cardiac cycle.

Conclusion. The presented method of qualitative computer assessment of the movement of the wire element of heart valve prosthesis using the “TiAra” bioprosthesis as an example demonstrates its validity as a tool for studying prosthesis functioning.

ONLINE. ORIGINAL STUDIES. Cardiovascular surgery

152-161 379
Abstract

Highlights. The article presents the outcomes of endovascular and minimally invasive atrial septal defect closure in children under the age of 3 and aged 3 to 18 years with subsequent assessment of heart remodeling.

Aim. To compare the outcome and features of cardiac remodeling (CR) in children under and over 3 years of age after minimally invasive (MI) and endovascular closure of atrial septal defect (ASD).

Methods. The retrospective single-center study included 100 children with secondary ASD who underwent endovascular and MI ASD closure. The patients were divided into 2 groups. The first group (n = 42) included children under the age of 3 years after MI and EC, the median age was 2 years [1.5; 3], and the second group (n = 58) included children aged 4-18 years after MI and EC, the median age was 7 years [6; 12], respectively, p = 0.001. According to the design of the study, the groups statistically differed in height and body weight (p = 0.001). According to the ASD diameter, there were no differences between the groups (p<0.05) in the number of patients with perforated atrial septal aneurysms and aortic rim deficiency. During inpatient care and 3–4 months after surgery, the outcome and indices of CR obtained by echo imaging were assessed.

Results. Surgical outcomes and medium-term follow-up analysis revealed that all children in both groups successfully underwent ASD closure in the absence of residual shunts. There were no hospital-acquired and medium-term complications. The length of hospital stay of children under 3 years was 7.5 days. [3; 9], which was significantly longer in comparison with the children of the older age group (3 days. [3;7]), (p = 0,001). ICU length of stay in the younger group of children was 24 hours [0; 24], while in the older group it was 0 days. [0; 24], p = 0,001. In the postoperative period, hemoglobin levels significantly decreased in children under 3 years of age (from 124.5 [119; 130] g/L, to 105 [97; 122] g/L, (p = 0.001)), while in the older age group this indicator remained the same. The analysis of features of CR during 3-4-month follow-up in both groups revealed that the initial changes indicating pathological CR were more pronounced in children older than 3 years. Significant dynamics of echocardiographic indices were observed in both groups during follow-up period, it manifested in the form of an increased volume and size of the left heart, and decreased volume and size of the right heart.

Conclusion. Endovascular  and  minimally  invasive ASD  closure  is  an  effective and  safe technique of ASD closure in children of various ages. In children over 3 years of age, pathological CR is initially more pronounced than in children under 3 years of age, indicating the expediency of an early ASD closure. At the same time, younger children  more  often  require  mechanical  ventilation,  cardiopulmonary  bypass, and a longer hospital stay and ICU stay. Higher number of EC performed in the group of young children could offset these negative consequences. Changes in CR indices after ASD closure in groups of children of different ages demonstrates comparable positive trends.

ONLINE. ORIGINAL STUDIES. Pathological physiology

162-176 507
Abstract

Highlights. The use of vascular smooth muscle cell markers, e.g. smooth muscle myosin heavy chain (SM-MHC) and alpha smooth muscle actin (α-SMA) for immunodetection of adventitial and perivascular microvessels (vasa vasorum) is preferrable over endothelial markers (CD31 and VE-cadherin) as it allows to define vascular geometry regardless of sectioning artifacts and provides ideal signal-to-noise ratio.

Aside from elastic laminae which discriminate arterioles from venules and capillaries, we were unable to confirm any specific markers of arterial, venous, and capillary differentiation, although KLF2 and PROX1 transcription factors indicated venous specification and HEY1 suggested capillary identity in rat aortas.

Aim. To develop an optimal approach to detection of microvessels and to evaluate the techniques for the differential immunostaining of arterioles, venules, and capillaries in human saphenous veins and rat aortas.

Methods. Saphenous veins excised during the coronary artery bypass graft surgery were used for the study. Serial cryosections were analyzed by means of haematoxylin and eosin and Russell-Movat’s pentachrome stainings and by immunofluorescent staining for endothelial cell markers (CD31 and VE-cadherin), vascular smooth muscle cell markers (SM-MHC and α-SMA), mechanosensitive transcription factors (KLF2 and KLF4), transcription factors of arterial specification (HES1, HEY1, ERG), transcription factors and markers of venous identity (NR2F2, NRP2), and transcription factors and markers of lymphatic lineage (PROX1, LYVE1, VEGFR3). Samples were visualized by light and confocal microscopy.

Results. In comparison with endothelial cell markers (CD31 and VE-cadherin), vascular smooth muscle cell markers (SM-MHC and α-SMA) permitted objective evaluation of vascular geometry and maximized signal-to-noise ratio irrespective of specific marker, microvessel specification or antibody used. Autofluorescence and specific histological  pattern  of  elastic  membranes  at  Russell-Movat’s  pentachrome staining allowed to discriminate arterioles from venules and capillaries. Albeit immunostaining of rat aortas found specific markers of venous endothelial cells (KLF2 and PROX1) and capillary endothelial cells (HEY1), these findings have not been confirmed in saphenous veins. We were unable to find specific markers of human venules and capillaries among the saphenous vein vasa vasorum despite an extensive screening of multiple markers.

Conclusion. Immunodetection of microvessels (e.g., vasa vasorum) should be performed by using vascular smooth muscle cell markers (SM-MHC and α-SMA) rather than endothelial cell markers (CD31 and VE-cadherin). Lack of specific markers to discern microvessels of different lineages suggests Russell-Movat’s pentachrome staining as an optimal option for the machine learning of neural networks to analyse the microvessels including vasa vasorum.

OONLINE . ORIGINAL STUDIES. Public health

177-187 712
Abstract

Highlights. It is necessary to manage adverse events in order to maintain health and safety of patients and medical workers in the process of healthcare. One of the tools that can improve the system of managing such events is the Poka-Yoke technique.

Aim. To theoretically justify and analyze the possibility of using lean manufacturing tools in the management of adverse events to ensure the quality and safety of healthcare.

Methods. The analysis of domestic and foreign literature, regulatory and legal documentation for the period from 2015 to 2021 was carried out. The following keywords were used as search terms: “adverse events”, “medical error”, “risk management in healthcare organization”, “Poka-Yoke technology”, “adverse events management system”. The Russian Science Citation Index database, “Garant” reference system and Google Scholar search engine were used to find full text publications. The analysis of public reports of government officials on the issues of improving the safety of healthcare was carried out. The methods of system and logical analysis were used for the analysis. The article presents the experience of developing an adverse events management system at the Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases” (Kemerovo, Russia).

Results. The analysis revealed a variety of approaches to management of adverse events. The authors believe that the “Poka-yoke” method, described in the set of national standards  and  technical  specifications maintained  by  the  Russian  Federation “GOST R 56407-2015 Lean manufacturing. Basic methods and tools”, can be implemented in the process of managing adverse events. The main advantage of Poka-yoke method is the fact that it is prevention-based; thus, it is possible to introduce the concept of zero defects in healthcare process. The experience of the Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases” confirms the expediency of using this technique for the development of the adverse events management system.

Conclusion. Implementation of the Poka-Yoke technique leads to the improvement in the adverse events management system.

ONLINE. CASE STUDY. Cardiovascular surgery

199-203 592
Abstract

Highlights. The paper presents a unique clinical case of patient with congenital heart defect known as Bland-White-Garland syndrome diagnosed in the adulthood. Takeuchi repair (creation an intrapulmonary tunnel) was carried out to treat this defect.

Background. An anomalous origin of the left coronary artery from the pulmonary artery (Bland-White-Garland syndrome) is an uncommon but severe pathology that requires immediate  surgical  treatment.  The  use  of  modern  diagnostic  methods  (both non-invasive and invasive) has resulted in higher prevalence of this syndrome, diagnosed not only in an early childhood, but also in adulthood. Recording each medical case and choosing an optimal treatment strategy will increase knowledge of this pathology and reduce the high risk of mortality. The paper presents a clinical case of this syndrome in an adult patient who had remained undiagnosed for a long time as the syndrome was masked under the clinical features of chronic heart failure. Takeuchi repair (creation an intrapulmonary tunnel) was carried out to treat this extremely rare defect for a patient of this age group.

ONLINE. REVIEW. Cardiovascular surgery

188-198 797
Abstract

Highlights. Mechanical thrombectomy is the “gold standard” treatment of patients with large-vessel occlusions. Five randomized trials conducted in 2015 made a significant contribution to the development and introduction of mechanical thrombectomy into clinical practice. The DAWN and DEFUSE-3 trials have provided new insights into the pathophysiology of ischemic stroke and ensured the advancement in the therapeutic field.

Abstract. Stroke is one of the leading causes of death and disability worldwide. The general strategy for the treatment of ischemic stroke is aimed at restoring blood flow to the ischemic regions of the brain. Intravenous thrombolysis has been the treatment for acute ischemic stroke since 1996. However, since 2015, as a result of 5 randomized trials, endovascular mechanical thrombectomy has become the gold standard for the treatment of patients with large cerebral artery occlusion. The DAWN and DEFUSE 3 trials have provided new insights into the pathophysiology of ischemic stroke, shifting the paradigm from “time = brain” to “collaterals = brain”. In this article, the authors will consider development of endovascular devices, modern mechanical thrombectomy techniques, and directions for further research of endovascular treatment for ischemic stroke.



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