Highlights

• Patients with IHD and complete coronary revascularization in history suffering from ADCHF should consider EMB to clarify the etiology of decompensation.
• According to the EMB results, concomitant myocarditis is diagnosed in the majority of patients with IHD and ADCHF.
• The results of immunohistochemistry indicate that patients with IHD and ADCHF often have antigen expression toward cardiotropic viruses.

Abstract

Aim. To compare the clinical and morphological profile of patients with acute decompensated chronic heart failure (ADCHF) with ischemic and non-ischemic etiology with the following determination of the antigen expression toward cardiotropic viruses in myocardium.

Methods. The observational study included 56 patients with ADCHF and LV EF <40%, the patients were divided into 2 groups: patients with ischemic heart disease (IHD) after complete coronary revascularization (n = 26) and patients without IHD (n = 30). All patients underwent standard clinical, instrumental and laboratory examinations (invasive coronary angiography and endomyocardial biopsy (EMB) with morphological analysis and determination of the antigen expression toward cardiotropic viruses).

Results. Patients with ischemic ADCHF presented with fewer rates of shortness of breath during hospitalization compared with patients with non-ischemic ADCHF (12 vs 53%, p = 0.001), fewer rates of wheezing (54 vs 74%, p = 0.014), lower heart rhythm (76 vs 90, p = 0.047) and lower respiratory rate (18.5 vs 22, p = 0.031), lower N-terminal prohormone of brain natriuretic peptide levels (403.1 vs 964.0 pg/mL, p = 0.019), and lower incidence of diffuse LV hypokinesis (58 vs 87%, p = 0.002), but ischemic ADCHF patients also presented with higher rates of edema of the lower extremities (46 vs 20%, p = 0.037) and atrioventricular blockade of varying degree (35 vs 7%, p<0.05). According to EMB data, concomitant myocarditis was diagnosed in 69% of patients with ischemic ADCHF and in 80% of patients with non-ischemic ADCHF. Patients in both groups were more likely to present with the expression of enterovirus antigens (77 and 80%), and less likely to present with the expression of human herpesvirus 6 (HHV-6, 50 and 53%) and Epstein-Barr virus antigens (EBV, 23 and 20%), respectively (there were no statistically significant differences).

Conclusions. Patients with ischemic ADCHF had less pronounced decompensation compared with patients with non-ischemic ADCHF. Patients with ischemic ADCHF have concomitant myocarditis in 69% of cases according to EMB. Enterovirus, HHV-6 and EBV antigens were the most commonly expressed antigens. Thus, the majority of patients with IHD and complete coronary revascularization in history had ADCHF due to a combination of IHD and viral myocarditis.

Highlights

• We propose serum biomarkers as risk assessment tools for patients with COVID-19.
• J-waves are a common ECG finding, detected in 4–6% of the population, and are a risk factor for ventricular tachycardia and mortality in COVID-19 patients.

Aim. To evaluate the prognostic potential of a combination of cardiac-specific biomarkers and ECG J-waves regarding long-term mortality and cardiovascular complications after discharge in patients with COVID-19-associated pneumonia.

Methods. Serum biomarkers sST2, VCAM-1 and hs-TnI were assessed at admission in 254 patients hospitalized with COVID-19-associated pneumonia. ECGs on admission were analyzed for the presence of J waves. Clinical and laboratory characteristics of patients, as well as biomarker concentrations and the presence of J-waves on the ECG, were correlated with mortality and cardiovascular complications after discharge at 12 months [FU: 347 (310, 449) days]. Cox proportional hazards models were used to identify predictors of the risk of mortality and the composite endpoint up to one year after discharge.

Results. A high level of VCAM-1 was a significant predictor of the risk of a combined endpoint (MI, stroke, pulmonary embolism, sudden death): HR = 1.049, CI 95%: 1.016–1.083; and high sST2 level was a significant predictor of the risk of both death (HR = 1.006, CI 95%: 1.004–1.007) and the composite endpoint (HR = 1.005, CI 95%: 1.003–1.006). In the generalized multivariate model, when other influencing factors were combined, the presence of a J-wave on the ECG during hospitalization was statistically insignificant (p > 0.5) for predicting sudden death up to a year after discharge.

Conclusion. In hospitalized COVID-19 survivors, elevated hsTnI and sST2 levels on admission were strong predictors of CV events during long-term follow-up. On the other hand, the significance of the J-wave on the ECG in predicting long-term CV events remains borderline.

Highlights

The complex role of the brain natriuretic peptide in the pathogenesis of arterial hypertension, as well as the successful use of the N-terminal fragment of the prohormone brain-type natriuretic peptide as a biomarker of cardiovascular diseases determine the relevance of this work.

Aim. To study the association between brain natriuretic peptide levels (NT-proBNP) and markers of the severity of resistant arterial hypertension.

Methods. The study included 40 patients with diagnosed resistant arterial hypertension (RAH) and 30 patients with AH. All patients underwent clinical examination and measurement of NT-proBNP levels before and after receiving standard antihypertensive therapy.

Results. Before receiving standardized antihypertensive therapy (AHT), NT-proBNP levels in the group of patients with RAH and in the group of patients with non-resistant hypertension did not differ significantly (p = 0.48), but systolic BP was statistically significantly higher (p = 0.039) in the group of patients with RAH. RAH revealed a direct association between NT-proBNP and sodium (r = 0,38; p = 0.01), as well as a direct association between NT-proBNP and body mass index (r = 0,32; p = 0.02). Factor analysis revealed a relationship between NT-proBNP and age (p < 0.01), as well as a direct relationship between NT-proBNP and potassium (r = 0,29; p = 0.04). After receiving standardized AHT, NT-proBNP levels decreased in the RAH group and in the non-resistant AH group (p = 0.03; p = 0.0001), but the decrease was less pronounced in the RAH group. NT-proBNP levels after standardized AHT in the RAH group were higher (p < 0.0001) compared to the non-resistant AH group, and relatively high NT-proBNP levels were directly associated with the presence of RAH (p = 0.0025).

Conclusion. The results of the study indicate the presence of an association between NT-proBNP levels and resistant arterial hypertension. Supposedly, this association determines the uncontrolled course of resistant arterial hypertension – desensitization of receptors that regulate vascular tone, lipid metabolism disorders and natriuresis dysfunction.

Highlights

We have developed an algorithm for selecting patients for CT pulmonary angiography in case of suspected pulmonary embolism. The algorithm is based on the results of laboratory studies, duplex ultrasound of the veins of the lower extremities and echocardiography. This algorithm makes it possible to reliably exclude pulmonary embolism in 21.2% of patients without performing CT pulmonary angiography.

Aim. To develop an algorithm for excluding pulmonary embolism and selecting patients for pulmonary angiography based on the results of laboratory and ultrasound studies.

Methods. The retrospective single-center study was conducted using the data of 113 patients admitted to the ICU with suspected pulmonary embolism. Patients underwent echocardiography and duplex ultrasound of the veins of both lower extremities, and computed tomography pulmonary angiography with contrast.

Results. We carried out comparative analysis of clinical and anamnestic data depending on the presence of pulmonary embolism. There were significant differences between the groups by gender (p = 0.008) and age (p = 0.042). The concentration of D-dimer in the group with pulmonary embolism was significantly higher than in the control group (p < 0.001). Moreover, the left ventricular ejection fraction was higher in the group with pulmonary embolism compared to controls (p < 0.001). According to ultrasound data, 59% of patients with pulmonary embolism showed signs of acute deep vein thrombosis of the lower extremities, which was significantly more common compared to the control group (p < 0.001).

Pulmonary angiography should be recommended to patients with suspected pulmonary embolism and signs of prior or acute deep vein thrombosis. In the absence of these signs and a D-dimer concentration of less than 1 500 ng/mL, pulmonary embolism can be reliably excluded. In cases where the concentration of D-dimer is less than 10 000 ng/mL and pulmonary artery systolic pressure is no more than 30 mmHg, then pulmonary embolism can be excluded as well. In all other cases, we recommend to perform pulmonary angiography.

Conclusion. We have developed an algorithm for excluding pulmonary embolism and selecting patients for pulmonary angiography. The algorithm makes it possible to increase the specificity of the study from 45.1% to 57.3%. The algorithm is based on the concentration of D-dimer and the results of noninvasive ultrasound diagnostics. Ultrasound examination of the deep veins of the lower extremities and echocardiography allow differential diagnosis of cardiac pathology and other causes of symptoms. Moreover, these methods can become the basis for the selection of patients for pulmonary angiography.

Highlights

Characteristics of IQ level in children with congenital heart disease are presented. The results of a study of IQ levels in children using Raven's progressive matrices are described.

Aim. The level of IQ assessment in children with congenital heart disease in the preoperative period.

Methods. A prospective IQ level was conducted using Raven's progressive matrices in children aged 8–14 years with septal congenital heart defects in the preoperative period on the basis of the Research Institute of Complex Problems of Cardiovascular Diseases.

Results. Among the 70 children included in this study, 22 patients had a documented ventricular septal defect, and 48 had a secondary type of atrial septal defect. According to the IQ test conducted using Raven's progressive matrices, it was revealed that the majority of children had average and below average intelligence (56% and 28%, respectively), and the weakest score in the use of “extraordinary intelligence” was noted in only 16% of cases. It should be noted that “highly developed intelligence” and “defective intellectual abilities” were not identified in any of the patients. Using logistic regression, predictive factors influencing the low IQ level in patients with congenital heart disease were identified, which were: a stable family history, heart failure clinic and comorbid background.

Conclusion. It is necessary to take into account studies of cognitive diseases in domestic children with congenital heart disease to adjust the correction already at the stage of preoperative preparation.

Highlights

Critical aortic coarctation (CoA) in newborns leads to severe pressure overload of the left ventricle (LV), myocardial damage, which is accompanied by a high risk of cardiogenic shock and sudden cardiac death. Palliative stenting of the aortic isthmus in critically ill newborns reduces the incidence of mortality in the hospital period and makes it possible to prepare the patient for radical surgical correction of the defect.

Aim. To compare immediate and long-term results of palliative stenting and surgical correction of critical aortic coarctation in newborns.

Methods. The single-center, retrospective study was conducted at the National Medical Research Center named after Academician E.N. Meshalkin. From 2008 to 2021, the Department of Congenital Heart Diseases performed surgical treatment of 85 patients with critical aortic coarctation. 11 patients were excluded from the study. All patients included in the study (74 patients) were divided into two groups: palliative stenting (n = 20; 27%) and primary surgery (n = 54; 73%). After PSM analysis, the groups were balanced by age, weight, gender, body surface area and lactate. 40 patients were selected: 20 in each group. There were no significant differences between baseline characteristics between the groups.

Results. The technical success of aortic coarctation stenting was 100%. The lethal outcome in the stenting group was in 2 (10%) cases, while in the primary surgery group it was in 11 (55.5%) cases, p = 0.048. Complications in the early postoperative period were higher in the open surgery group. Long-term complications did not differ between groups and had an equal incidence of development.

Conclusions. Palliative stenting of critical aortic coarctation is associated with lower mortality during hospital stay compared with primary surgical correction (10% vs 55.5%, p = 0.048). Multiple organ failure in the early postoperative period is an independent risk factor (HR 102; 95% CI 3.5–295, p < 0.01) of death. Patients with critical aortic coarctation after primary surgical correction have a higher incidence of early postoperative complications in comparison with patients with palliative stenting (80% vs 40%, p = 0.02). The only risk factor for multiple organ failure (HR 22.8; 95% CI 4.1–302, p = 0.03) and/or acute renal failure (HR 17.6; 95% CI 1.3–238, p = 0.02) is primary surgical correction of the defect. The main risk factor for abdominal syndrome are patients operated with cardiopulmonary bypass (HR 19; 95% CI 4.8–280, p = 0.01). Long-term complications do not differ between groups and have an equal frequency of occurrence.

Highlights

• The review describes the outcomes of right ventricular outflow tract stenting in children with the tetralogy of Fallot.
• The features of stent explantation and further functioning of the pulmonary artery valve after surgery are analyzed.

Aim. To analyze the technical aspects related to the explantation of stents from right ventricular outflow tract (RVOT) and repair of the pulmonary artery valve during radical correction (RC) of tetralogy of Fallot (TOF), and the results of subsequent surgical treatment of these patients.

Methods. The study included 25 children with a cyanotic TOF who received a two-stage correction of CHD (stage 1 – RVOT stenting, stage 2 – RC of TOF).

Results. Shortly after RVOT stenting, we noted positive changes in the condition of children. The median of arterial oxygen saturation rose from 80% to 95%, the gradient on RVOT decreased from 72 to 53 mmHg. After 3 months children underwent RC of TOF. Patients received palliative care in the form of RVOT stenting with a low complication rate, only 4% of patients had a fatal outcome. During RC of TOF, there were no technical difficulties regarding explantation of the stent from RVOT. The thirty-day survival rate was 96%. During RC 16% of patients avoided transannular repair procedure.

Conclusion. The patients were provided with effective palliative care such as RVOT stenting, which was reflected by improved oxygenation after the procedure and optimal growth of the pulmonary arteria and left ventricle by the time of RC. There were no technical difficulties regarding the explantation of the stent from RVOT during RC.

Highlights

The review presents the results of valve-sparing and reconstructive aortic root surgeries. The results of the analysis of patients` data can help specialists to compare and develop novel approaches to the treatment of patients with aortic root diseases. The presented “Russian conduit” procedure developed by the authors is an option for treatment of the aortic valve and aortic root defects.

Aim. To develop an optimal technique for surgical treatment of aortic root pathologies. The review presents data on modern surgical approaches in the management of the disease, including the Bentall-De Bono procedure, “classic” and “modified” David procedures, the “Russian Conduit” procedure, and the Ross procedure.

Methods. The retrospective study involved 183 patients who underwent surgeries for aortic root pathologies. Patients were divided into five groups based on the surgical techniques. Clinical and laboratory data were evaluated in the mid-term postoperative period. Statistical analysis included comparative methods using various criteria and tests.

Results. The David procedure was advantageous over the Bentall-De Bono procedure for patients with intact aortic valve leaflets. The “Russian conduit” procedure demonstrated safety and durability comparable to the classic David procedure, along with good hemodynamic performance. There was a higher frequency of residual aortic regurgitation following leaflet repair within the “modified” David procedure.

Conclusion. The results confirm that techniques using autologous tissues, such as the “Russian conduit” and “Protected Ross” are effective and safe alternatives to traditional replacement methods. The David procedure remains preferable for patients without leaflet damage, while procedures involving complete replacement are advisable for patients with severe valve pathology.

Highlights

Despite the widespread use of thoracoscopic ablations in the treatment of atrial fibrillation, accurate predictors of recurrent arrhythmia have not been established, therefore, the effectiveness of this procedure varies significantly (from 38 to 83%). According to clinical guidelines, thoracoscopic ablation should be considered in patients after primary catheter ablation. Several studies have noted that patients with a catheter ablation in history have a significantly higher risk of recurrent atrial fibrillation after thoracoscopic ablation compared with patients without catheter ablation in the 5-year follow-up period. However, our study results indicated similar prevalence of recurrent arrhythmia in patients with and without catheter ablation. Taking into account all of the above, we have evaluated the impact of previous catheter ablations on the effectiveness of thoracoscopic ablation of atrial fibrillation in the long-term follow-up period.

Aim. To assess the impact of failed pulmonary vein catheter ablation (CA) on the efficacy and safety of thoracoscopic ablation (TSA) in the long-term follow-up period.

Material and Methods. “Box lesion” TSA with left atrial auricle (LAA) exclusion was performed in 47 patients with CA in history and 103 patients without CA. The procedure was considered effective in the absence on 24-h HM ECG of any atrial tachyarrhythmia of more than 30 seconds duration recorded at the examination checkpoints.   

Results. The efficiency of TSA in the group with CA was 61,5% and 77,5% in the group without CA, with a mean follow-up period of 2,6 ± 0,83 years. Univariate and multivariate Cox proportional hazards analyses showed that prior CA statistically significantly increased the risks of atrial tachyarrhythmia recurrence by 1,936-fold (95% CI 1,931–4,026, p = 0,037) and 1,917-fold (95% CI 1,913–4,098, p = 0,042), respectively. 

Conclusion. The study results revealed that previous unsuccessful pulmonary vein CA may reduce the effectiveness of TSA in the long-term follow-up period. However, this topic requires further research involving multivariate analysis on a larger cohort of patients.

Highlights

The presented study is relevant due to high incidence of cognitive impairment during cardiac surgery in children. The article describes and proves the effectiveness of a cerebral protection strategy using ketamine infusion in subanesthetic doses.

Abstract

Aim. To assess the effectiveness of ketamine infusion in the postoperative period for neuroprotection in children during surgical correction of congenital septal heart defects.

Methods. The study included 68 patients aged from 1 to 60 months and weighing from 3.9 to 19.5 kg who underwent correction of atrial or ventricular septal defect with cardiopulmonary bypass. All subjects were randomized into three groups: patients in the study group-1 (SG-1) received ketamine infusion after the completion of surgery and for the next 16 hours at a dose of 0.1 mg/kg/hour; patients in study group-2 (SG-2) received ketamine at a dose of 0.2 mg/kg/hour, and patients in the control group (CG) did not receive ketamine. To analyze the severity of damage to the neurovascular unit, the following specific serum markers were used: S-100-ß, neuron-specific enolase, glial fibrillary acidic protein, occludin and claudin-1. Blood for analysis of marker concentrations was collected at 3 control points: 1 – before the start of the operation, 2 – immediately after completion of cardiopulmonary bypass, 3 – 16 hours after the operation.

Results. The groups were comparable in terms of pre- and intraoperative characteristics. S-100-ß protein in patients who received 0.1 mg/kg/hour ketamine did not differ from controls, but patients who received 0.2 mg/kg/hour ketamine showed statistically significant differences compared to the group with lower concentrations. Neurospecific enolase had lower concentrations in both study groups compared to the controls. Occludin showed a significantly lower concentration only in the group with a ketamine dose of 0.2 mg/kg/hour. Glial fibrillary acidic protein and claudin-1 concentrations did not differ between groups.

Conclusions. The study results showed the effectiveness of using ketamine infusion at a dose of 0.1 and 0.2 mg/kg/hour for cerebral protection in children in the postoperative period of correction of congenital septal heart defects. Moreover, they proved that a ketamine dose of 0.2 mg/kg/hour has a more pronounced neuroprotective effect.

Highlights

Abdominal surgeries are complicated by an infectious process, the development of which significantly aggravates the underlying disease, lengthens the patient’s stay in the hospital, increases the cost of treatment, causes deaths and negatively affects the recovery time of operated patients. In order to prevent the formation of adhesions and the development of infection, it is promising to use anti-adhesion membranes that have their own antibacterial activity.

Aim. To study the antibacterial activity of biodegradable membranes containing tigecycline upon implantation into an infected wound in a laboratory animal model.

Methods. We used the following composition of biodegradable polymers for the manufacture of membranes: copolymer polylactide-co-glycolide (50:50) Mm 20-30 KDa and polylactide-co-glycolide (85:15). We dissolved the polymers were in 1,1,1,3,3,3-Hexafluoroisopropanol, and to impart antibacterial properties to the membrane, we added the antibiotic tigecycline to the membrane composition, and assessed the optimal concentration of the antibiotic. We prepared the membranes using electrospinning. To evaluate the antibacterial effectiveness of membranes when implanted into a wound infected with Staphylococcus aureus we used an animal model (rat).

Results. The prepared membranes containing tigecycline at a concentration of 0.5 mg/mL solution exerted maximum antibacterial effect. When implanted into an infected wound in laboratory animals, membranes containing tigecycline effectively suppressed the infectious process. By the 14^th day of follow-up, we noted a complete healing of the wound, the absence of an inflammatory reaction, moreover we histologically confirmed an active infectious process.

Conclusion. Biodegradable polymer membranes containing tigecycline as an antibacterial component effectively suppress the infectious process in an animal experiment.

Highlights

In the modern literature, the algorithms for managing patients with CKD and ACS are not fully covered. However, approximately one in three ACS patients has CKD. To date, the frequency of using radial arterial access and intravascular imaging in patients with ACS and CKD in clinical practice is increasing, which significantly improves outcomes. However, many topics related to these issues remain poorly understood, so it is necessary to conduct specialized studies among all stages of CKD, taking into account eGFR, and the severity of albuminuria.

Abstract

The number of patients suffering from chronic kidney disease (CKD) is growing progressively, in half of the cases they die from cardiovascular diseases (CVD) before they reach the terminal stage of renal failure. Patients with CKD belong to a special group of the population when considering ACS therapy. CKD complicates diagnosis, risk stratification, pharmacological therapy, invasive treatment, and ACS outcomes. The purpose of the review is to analyze the domestic and foreign literature on the management of ACS in patients with CKD, as well as to offer practical recommendations for practitioners and identify current knowledge gaps that require further research. ACS makes a significant contribution to the morbidity and mortality of patients with CKD, which makes it extremely relevant to study the features of ACS management in this group of patients. It is not uncommon for patients and clinicians to reject scientifically based diagnostic and therapeutic methods due to concerns about worsening renal failure. Although overcoming this phenomenon partly depends on following the recommendations, a complete solution to the problem will equally depend on a proper assessment of the risks, pharmacological and invasive factors characteristic of patients with CKD. To date, the frequency of using radial arterial access and intravascular imaging in patients with ACS and CKD in clinical practice is increasing, which significantly improves outcomes. Nevertheless, a large number of knowledge gaps remain, so it is necessary to conduct specialized studies among all stages of CKD, not only taking into account eGFR, but also the severity of albuminuria. It is important to note that this will require better representation of CKD patients in randomized trials.

Highlights
Spontaneous coronary artery dissection (SСAD) is recognized as an important cause of acute myocardial infarction (AMI), especially in young and middle-aged women. Polygenic assessment is currently limited due to the lack of diversity in most large-scale SСAD studies, which tend to have a significant bias towards patients of European origin or study exclusively individuals of European origin. Further studies involving larger and more diverse populations are needed to better understand the various vascular biological mechanisms underlying SСAD and CHD as two different causes of AMI.

Abstract
Spontaneous coronary artery dissection (SСAD) is recognized as an important cause of acute myocardial infarction (AMI), especially in young and middle-aged women. Studies have revealed the complex genetic architecture underlying SСAD, with variants with different effect sizes playing a role. The purpose of the study is to analyze the current literature on the genetic and clinical factors of SСAD, highlighting those unique factors that distinguish SСAD from atherosclerotic lesions leading to AMI. The primary sources were searched in the electronic databases PubMed, eLibrary and Google Scholar. When identifying both rare and common genetic variations in patients with this pathology, a wide variety of potential genetic mechanisms associated with endothelial cells, extracellular matrix and blood coagulation cascade were revealed. A genetic study of DMCA has revealed important positive links between this disease and other systemic arteriopathies, as well as striking negative links with coronary heart disease and MI. The results have led to the emergence of a new clinical and genetic spectrum of AMI, which may be important for the treatment of AMI, especially in young female patients.

Highlights

• The review delves into the proposed concept of the morphofunctional arterial conduit system used in open heart surgery.
• Based on this concept, the review presents analogous morphofunctional stent/balloon-artery system for endovascular treatment of coronary artery disease.

Abstract

 The review article describes potential modeling of the interaction between a stent/balloon and a coronary artery analogous to and based on the previously proposed concept of the morphofunctional arterial conduit system. The system substantiates the advantages and disadvantages of various techniques of coronary artery bypass grafting and should be accounted for when choosing a stent. This interaction during endovascular treatment of coronary artery disease is of great importance for the development of new generation of devices, as well as for the management of various factors involved in the prevention of stent dysfunction and progression of coronary atherosclerosis.

Highlights

• 3D modeling is a complex process that requires collaboration of specialists from various fields, such as radiologists, cardiologists, cardiac surgeons and engineers.
• The use of 3D imaging systems is especially relevant in the field of congenital heart defects due to the diversity of anatomical variations.
• To date, such systems are being actively introduced into the medical industry, in particular in the surgical treatment of congenital heart defects.

Abstract

Alongside traditional visualization methods, 3D modeling of the heart and blood vessels is an attractive tool that complements the assessment of congenital heart defect anatomy. With technological advancements, there is active integration of such systems into the medical industry. The use of 3D visualization systems is especially relevant in the field of congenital heart defects due to the diversity of anatomical variations. With advanced image post-processing technologies, it becomes possible to obtain realistic models and simulations of complex congenital heart defects in patients, which is crucial for both diagnosis and treatment planning. This review summarizes the current capabilities of 3D modeling in the field of congenital heart defect surgery, and describes the prospects of using such technologies in daily clinical practice.

Highlights

• Modeling proinflammatory endothelial dysfunction in vitro is achieved by inducing mitochondrial-oxidative stress (alkylating agent mitomycin C), lysosomal-calcium stress (calciprotein particles), cytokine stress (lipopolysaccharide addition), or metabolic stress (palmitic acid addition). In vivo, this can be modeled by comparing aged and young laboratory rodents (specifically hyperlipidemic mice).
• To model vasospastic endothelial dysfunction in vitro, it is advisable to use inhibitors of endothelial NO synthase. For in vivo modeling, rats with stress-induced hereditary arterial hypertension (SIHAH) should be used, comparing them with normotensive Wistar rats in experiments.
• For modeling prothrombotic endothelial dysfunction, it is appropriate to use the S1 subunit of the Spike protein of the SARS-CoV-2 virus or its receptor-binding domain (RBD), as well as transgenic K18-hACE2 mice expressing the human ACE2 receptor.

Abstract

Despite its high clinical relevance to a range of acute (COVID-19, sepsis, multiple organ failure) and chronic (arterial hypertension, frailty syndrome, deep vein thrombosis) conditions and its direct impact on the development of adverse outcomes, the concept of endothelial dysfunction remains rather vague. Considering the various triggers, development mechanisms, molecular markers, and pathological consequences, it is reasonable to classify endothelial dysfunction as a typical pathological process into three types, determined by the leading pathogenetic factor: proinflammatory, vasospastic, and prothrombotic. Except for the hemostatically active high-molecular-weight multimers of von Willebrand factor accompanying the development of prothrombotic endothelial dysfunction in COVID-19, reliable and clinically applicable circulating markers of endothelial dysfunction remain unknown, significantly complicating the study of therapeutic correction methods. This review discusses approaches to modeling these types of endothelial dysfunction in cell cultures and animal models, as well as clinical scenarios for verifying potential markers identified in experiments. For modeling proinflammatory endothelial dysfunction in vitro, it is optimal to use mitomycin C, calciprotein particles, lipopolysaccharide, and palmitic acid; for vasospastic dysfunction – endothelial NO synthase inhibitors; for prothrombotic dysfunction – the S1 subunit of the SARS-CoV-2 Spike protein or its receptor-binding domain. For modeling proinflammatory endothelial dysfunction in vivo, mitomycin C is proposed; for vasospastic dysfunction – rats with hereditary baseline and stress-induced arterial hypertension; for prothrombotic dysfunction – intravenous administration of the S1 subunit or its receptor-binding domain to transgenic mice expressing the human ACE2 receptor (K18-hACE2). The systematic search for markers of endothelial dysfunction is based on step-by-step mass spectrometric profiling and dot-blot profiling (or multiplex immunofluorescent assay based on magnetic microspheres) of the cellular secretome (in serum-free culture medium) and blood serum (after fractionation and removal of high-molecular-weight proteins and supramolecular complexes), followed by verification of the selected markers using enzyme-linked immunosorbent assay.

Highlights

• Potential cellular markers of vasospastic endothelial dysfunction include endothelial NO synthase and its phosphorylated forms, mechanosensitive transcription factors, as well as markers of nitrosative and oxidative stress.
• Probable cellular markers of proinflammatory endothelial dysfunction may encompass transcription factors of the endothelial-mesenchymal transition, proinflammatory transcription factors, mechanosensitive transcription factors, inducible cell adhesion molecules, components of the basement membrane, and key endothelial integrins.
• Cellular markers of prothrombotic endothelial dysfunction may include components of the endothelial glycocalyx, as well as membrane and cytoplasmic anti- and prothrombotic molecules responsible for regulating local and systemic hemostasis.

Abstract

This review examines several groups of potential cellular markers for various types of endothelial dysfunction: vasospastic, proinflammatory, and prothrombotic. For this purpose, we screened the PubMed database for the respective publications over the past 45 years. Immunohistochemical analysis of the development of vasospastic endothelial dysfunction involves measuring the expression of endothelial NO synthase and its phosphorylated forms (serine-113/117, threonine-495, serine-632, serine-1176/1177), mechanosensitive transcription factors (KLF2, KLF4, and NRF2), markers of nitrosative stress (3-nitrotyrosine and 6-nitrotryptophan), and oxidative stress markers (proteins associated with malondialdehyde or methylglyoxal, xanthine oxidase, and isoforms of NADPH oxidase NOX1, NOX2, NOX4, and NOX5). Potential immunohistochemical markers of proinflammatory endothelial dysfunction include N-cadherin as a mesenchymal cell marker in combination with the loss of endothelial markers (CD31 and VE-cadherin), transcription factors of endothelial-mesenchymal transition (Snail, Slug, Twist1, and Zeb1), proinflammatory transcription factors (NF-κB, IRF1, IRF3, IRF5, IRF7, AP-1, ATF1, ATF2, ATF3, ATF4, ATF6, EGR-1, EGR-3, STAT1, STAT3, and STAT4), NLRP3 as a marker of inflammasomes, the aforementioned mechanosensitive transcription factors, inducible cell adhesion molecules (VCAM1, ICAM1, E-selectin), as well as components of the basement membrane (laminin, type IV collagen, nidogen-1, nidogen-2, perlecan, fibronectin) and endothelial integrins (α2β1, α3β1, α5β1, α9β1, αvβ3, αvβ5). Immunohistochemical analysis of prothrombotic endothelial dysfunction may rely on assessing the expression of components of the endothelial glycocalyx (via immunofluorescent staining with UEA-1, which binds to fucosylated glycans, or through immunohistochemical staining for syndecan-1, heparan sulfate, chondroitin sulfate, hyaluronic acid, perlecan, and glypican-1), as well as evaluating the expression of its antithrombotic (antithrombin III, tissue factor inhibitor, thrombomodulin, CD39, CD73) or prothrombotic proteins (heparanase, hyaluronidase, angiotensin-converting enzyme 2, von Willebrand factor). Verification of immunohistochemical markers differentially expressed in control and model animals should be conducted using electron microscopy of adjacent vascular segments to establish associative and correlative relationships between molecular and pathomorphological markers.

Highlights

The review describes a rare clinical case of isolated left ventricular apical hypoplasia with atrial septal defect.

Abstract

Isolated left ventricular apical hypoplasia is characterized by impaired left ventricle. The frequency of the disease is 0.5-0.75% and it can be easily detected on echocardiography. The disease is difficult to diagnose due to absence of symptoms, therefore timely diagnosis and treatment can prevent any complications and improve the quality of life.

Highlights

Treatment of coronary lesion and severe aortic stenosis in patients with comorbidities remains a serious issue. Specialists are still debating the appropriate treatment strategy and number of stages of interventions. The uniqueness of the presented case lies in the fact that stenting and transcatheter implantation of the aortic valve were urgently performed in a patient with acute coronary syndrome and severe aortic stenosis. The presented case indicates it is preferable to perform a combined procedure.

Abstract

This paper presents a clinical case of successful treatment of a 72-year-old patient with left main disease and severe degenerative aortic valve stenosis with poor left ventricular ejection fraction. On the second day after admission to the hospital, the patient developed acute myocardial infarction. He underwent emergency percutaneous coronary intervention. However, hemodynamic instability and pulmonary edema persisted. Heart team performed emergency transcatheter transapical aortic valve implantation (MedLab-CT №27), which allowed specialists to stabilize the patient`s condition. The postoperative period proceeded without significant complications; the patient was discharged on the 12^th day.

The members of the working group confirmed no conflict of interest or financial support.