Aim. To analyze associations of interleukin-6 receptor gene (IL6R) polymorphism (rs2228145) with the clinical course characteristics of hypertrophic cardiomyopathy (HCM) in groups of patients with various cardiometabolic risk factors

Material and methods. The sample consisted of 123 patients with HCM. The age  of the included patients ranged from 18 to 91 years (59 [41; 66.5]), of whom 59 were men, 64 — women. Two age groups were identified: the first group included patients from 18 to 44 years old, the second — 45 years and older. The control group consisted of 200 people without cardiovascular diseases and other severe comorbidities.

For genetic testing, DNA was isolated from peripheral blood lymphocytes. Genotyping of the IL6R gene polymorphism (rs2228145) was carried out by realtime polymerase chain reaction.

Results. A significant prevalence of CC genotype of the IL6R gene polymorphism (rs2228145) was revealed in patients aged ³45 years compared with the control group, which occurred in 14,1% and 3,0% of cases, respectively (CC:AC+AA, odds ratio (OR), 0,885, 95% confidence interval (CI), 1,051-0,691, p=0,006), and insignificant prevalence of C allele in this group, which does not reach the level of significance (A:C, OR, 0,870, 95% CI, 0,427-1,02, p=0,06). The prevalence of CC genotype (15,1% vs 3,0%) and C allele (39,0% vs 29,0%) was revealed in patients with HCM in combination with hypertension (HTN) compared with the control group (CC:AS+AA, OR=0,174, 95% CI, 0,047-0,650), p=0,004); (A:C, OR=0,638, 95% CI, 0,406-1,002), p=0,05).

Conclusion. The relationship between the IL6R gene polymorphism (rs2228145) and HTN in patients with HCM was confirmed. The presence of CC genotype and C allele of the rs2228145 IL6R gene polymorphism is significantly more common in patients with HCM with the disease onset ³45 years of age. The presence of CC genotype and C allele of the IL6R gene polymorphism (rs2228145) is associated with HTN in patients with HCM.

Aim. To study the associations of polymorphisms in F2, F7, and PAI1 genes with the presence of vulnerable plaque in coronary arteries (CA) and the blood concentration of proteins encoded by these genes.

Material and methods. The study included 101 men 40-70 years old with documented coronary atherosclerosis, who underwent coronary artery bypass grafting. According to the histological analysis of atherosclerotic plaques, men were divided into 2 groups: 40 men (39,6%) with stable plaque; 61 men (60,4%) with vulnerable plaques in CA. Genotyping of rs1799963 and rs6046 was performed by reverse transcription polymerase chain reaction, rs1799889 — by polymerase chain reaction. Statistical processing was performed using the SPSS 16.0 software package.

Results. In patients with stable plaques, allele A of rs6046 polymorphism in the F7 gene was observed in 2,9 times more often (95% confidence interval (CI), 1,20-7,20, p=0,021) than in men with vulnerable plaques. The odds ratio of the GA genotype carriage is 4,03 times higher among patients with stable plaques in CA compared with vulnerable plaques (95% CI, 1,49-10,93, p=0,006). The odds ratio of the 5G/4G genotype carriage among patients with stable plaques in CA is 2,47 times higher than in patients with vulnerable plaques (95% CI, 1,08-5,62, p=0,039). The 4G/4G genotype carriage is 5,85 times much more common in men with stable plaques (95% CI, 1,61-21,34, p=0,003).

Conclusion. Polymorphism in the PAI1 (rs1799889) and F7 (rs6046) genes are associated with the presence of vulnerable plaques in CA in men with verified coronary atherosclerosis. There were no differences between the groups in the frequencies of genotypes and alleles of the rs1799963 polymorphism of the F2 gene. Also, no significant differences were found in the blood levels of PAI-1 and factor VII in groups with different genotypes.

Aim. To search for causal mutations in candidate genes responsible for the development of sudden cardiac death (SCD) in men who died under the age of 45.

Material and methods. The SCD group (n=37) was formed using the criteria the World Health Organization and the European Society of Cardiology. Autopsy material was collected from men who died suddenly outside medical institutions and underwent forensic medical examination according to the standard protocol. Autopsy revealed no morphological changes that could explain sudden death. The mean age was 32,4±6,4 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform extraction. Clinical exome sequencing was performed. At first, we analyzed the results of sequencing of 24 genes, mutations in which lead to cardiovascular diseases associated with an increased risk of SCD: KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, CACNA1C, CALM1, CALM2, CAV3, KCNE1, KNCJNE2, KCNE2, SCN4B, SNTA1, MYH2, APOB, KCNA5, TGFB3, NEB, PDX1, FLNC, PLEC, KCND3.

Results. Of 37 samples, we revealed 13 probable pathogenic missense mutations in 9 samples (24,3%). Of 13 probable pathogenic variants, 5 were new.

Conclusion. This pilot study provides following conclusions: it is necessary to continue molecular autopsy research in Russia; to increase the effectiveness of detecting causal mutations, it is necessary to reduce the age of patients with SCD included in the study; studying the families of deceased; cooperation of experienced specialists — forensic pathologist, laboratory geneticist, cardiologist.

Aim. Comparative analysis of the deoxyribonucleic acid (DNA) methylation level in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes (9p21.3 locus) in vessels with/without atherosclerotic lesions, as well as in leukocytes of patients with clinically relevant carotid artery (CA) atherosclerosis and healthy individuals.

Material and methods. The group of patients with clinically relevant atherosclerosis included 22 individuals with severe stenosis (>80%) of CA. Samples of atherosclerotic plaques, presenting CA regions, and great saphenous veins, as well as peripheral blood samples (leukocytes) were obtained from patients. The control group consisted of 14 individuals with the mild CA stenosis (£24%) and without hemodynamically relevant changes; peripheral blood samples were obtained from each of them. DNA methylation level was assessed by targeted bisulfite sequencing of amplicons.

Results. The tissue-specific methylation of 31 CpG-site in the CDKN2A/2B and CDKN2B-AS1 gene enhancer was established: the vascular tissues significantly differed from the peripheral blood leukocytes. At the same time, there was an increase in the methylation level of both certain CpG sites and whole analyzed CA region affected by atherosclerosis (48,6 [34,8; 62,0]%), compared with intact vessels, both arteries (25,2 [23,1; 41,60]%, p=0,0001) and veins (35,0 [31,6; 40,0]%, p=0,0039). Patients had lower methylation levels in all CpG sites in blood leukocytes compared to blood vessel samples (8,7 [6,1; 9,7]%; p<0,05). At the same time, the level of DNA methylation in the blood leukocytes of atherosclerotic patients does not differ from that in healthy individuals (9,3 [8,3; 13,6]%; p>0,8).

Conclusion. In the present study, the relationship between an increase in the DNA methylation in the enhancer of the CDKN2A/2B and CDKN2B-AS1 genes in CA and their atherosclerotic lesions was revealed, as well as the tissue-specific DNA methylation between vessels and peripheral blood leukocytes.

Aim. To determine the relationship between the serum interleukin (IL) 18 level, the carriage of variant alleles IL18, IL18R1, IL18RAP and the risks of myocardial infarction (MI), hypertension, multifocal atherosclerosis in patients with stable coronary artery disease (CAD).

Material and methods. Two hundred and sixty patients with stable coronary artery disease living in a large industrial region ofWestern Siberia were examined. Serum IL18 concentrations was determined by the enzyme immunoassay. Genotyping was performed by real-time polymerase chain reaction using TaqMan technology.

Results. We revealed associations of rs13015714 IL18R1 and rs917997 IL18RAP sites with the MI risk (odds ratio (OR), 1,95 [95% confidence interval (CI), 1,063,58], p=0,029; OR, 2,01 [95% CI, 1,11-3,64], p=0,018, respectively). Associations of rs13015714 and rs917997 sites with high IL18 concentrations (genotypes C/T + T/T 488,0 [321,0, 687,2] pg/ml and T/G + G/G 504,2 [275,6; 655,5] pg/ml) was observed.

Conclusion. The relationship between the minor alleles of rs13015714 IL18R1 and rs917997 IL18RAP sites with an increased risk of MI in patients with stable CAD was shown. Also, polymorphism at rs13015714 and rs917997 sites provides different levels of circulating IL18. In particular, the carriage of minor alleles is associated with increased IL-18 levels in patients with previous MI and multifocal atherosclerosis or hypertension, as well as with an increase in the risk of these pathologies.

Aim. To study the expression patterns of matrix metalloproteinases (MMPs) -1, -2, -9, -12 in the leaflets of the epoxy-treated bioprostheses explanted due to dysfunction and to identify the pathways for the accumulation of these enzymes in the xenogenic tissues.

Methods. 19 leaflets from seven epoxy-treated bioprostheses (Kemcor (n = 2), PeriCor (n = 2), UniLine (n = 2) and TiAra (n = 1)) explanted from the mitral or aortic positions during repeat heart valve replacements were included in a study. Sections for microscopic studies were cut on a standard rotary microtome. Cell typing and the expression of MMP-1, -2, -9, -12 were evaluated using immunohistochemical staining with the antibodies against PTPRC/CD45, CD68, neutrophil myeloperoxidase and the corresponding MMPs. Stained samples were examined by light microscopy.

Results. Sporadic cell infiltrates, mainly composed of macrophages (PTPRC/CD45⁺, CD68⁺), were found in 17 leaflets from six explanted bioprostheses. Positive staining for MMP-1, -2, -9, -12 was colocalized with immune cell infiltrates. It is worth noting that MMP-9 staining was visualized even in the absence of cell infiltration, while more intense staining was found in the areas with a loose extracellular matrix. There were no signs of macrophage infiltration or MMP expression in xenotissues of pericardial bioprostheses failed due to thrombosis and explanted two days after implantation. However, a blood clot formed on its surface showed intense MMP-9 staining and included a large proportion of neutrophils positive for myeloperoxidase.

Conclusion. Macrophages and other immune cells that infiltrate xenotissues of epoxy-treated bioprostheses are sources of MMP-1, -2, -9, -12. In addition, MMP-9 can diffuse into bioprosthetic valve leaflets from blood plasma of patients. Thus, MMPs deposition in xenotissues may contribute to the leaflet ruptures and calcifications leading to the development of bioprosthetic valve dysfunction.

Aim. To study the relationship of matrix metalloproteinase-3 (MMP3) genetic polymorphism and dilated ischemic cardiomyopathy (DCM), as well as idiopathic cardiomyopathy (ICM) of unknown etiology.

Material and methods. A total of 221 patients with DCM and ICM were examined (mean age, 55,30±9,69 years). The group of ischemic DCM consisted of 111 people (99 men (89,2%) and 12 women (10,8%)). The mean age of DCM subjects was 51,73±9,74 years (male subgroup, 51,00±8,96 years; female subgroup, 57,75±3,71 years). The ICM group consisted of 110 people (100 men (91,5%) and 10 women (8.5%)). The mean age of ICM subjects was 58,68±8.38 years (male subgroup, 58,29±8.,6 years; female subgroup, 62,90±6,29 years). The control group of subjects (n=121) consisted of healthy people without cardiovascular diseases (mean age, 53,6±4,8 years). All patients of the experimental group underwent routine diagnostic tests, as well as coronary angiography. In case of suspected myocarditis, cardiac magnetic resonance imaging was performed. All patients underwent polymerase chain reaction to determine the MMP3-11715A/6A polymorphism (rs35068180).

Results. In patients with cardiomyopathy, regardless of the disease origin, significant differences were verified in comparison with the control group. Allele 6A (65,8% vs 59,3%, p=0,044) and genotype 6A/6A (42,1% vs 32,6%, p=0,099) were found significantly more frequently in patients with cardiomyopathy than in the control group. In addition, despite various etiological factors, the pathogenetic involvement of MMP3 is likely to have a general direction.

Conclusion. In all patients with cardiomyopathy, the prevalence of MMP3 gene A allele was shown. Due to decrease in the transcription activity in homozygous 6A allele, the stromelysin level in arterial walls also decreases. This promotes the activation of procollagenase-1, the deposition of extracellular matrix and cardiac remodeling

Aim. To study the association of genetic variants in the titin gene (TTN) with the development and clinical course of left ventricular noncompaction in different age groups.

Material and methods. The article discusses three clinical cases of patients with left ventricular noncompaction who were treated at theAlmazovNationalMedicalResearchCenter. We performed a new-generation sequencing of 108 genes associated with cardiomyopathies, as well as whole exome sequencing and Sanger sequencing.

Results. We identified genetic variants in the TTN gene leading to the synthesis of truncated protein: in the first two cases, the cause of noncompaction was a thirteen nucleotide deletion with a reading frame shift, in the second, a nonsense mutation. An algorithm for assessing the pathogenicity of the identified variants and a scheme of diagnostic genetic search are presented.

Conclusion. Causal role of TTN-truncating variants in development of cardiomyopathies and, in particular, left ventricular noncompaction, requires a comprehensive clinical, segregation and bioinformatic analysis using international databases and the use of bioinformatics software.

Aim. To study molecular biomarkers in patients with type 2 diabetes (T2D) in combination with heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) and compare the data obtained with clinical characteristics of myocardial remodeling.

Material and methods. The study included 42 patients with T2D (men — 53%, mean age — 60 years) with clinical manifestations of class II HF: 29 patients with HFpEF (group 1) and 13 patients with HFmrEF (group 2). The control group consisted of 13 healthy people, which were comparable in sex and age and had a normal body mass index (BMI). Patients received stable glucose-lowering and optimal drug therapy for HF for 3 months prior to enrollment in the study. Patients with HFpEF and HFmrEF were comparable in clinical and demographic parameters, had glycated hemoglobin (HbA ) of 8,5% and 8,8%, respectively (p>0,05), increased BMI or grade I-II obesity.

We studied following biomarkers: NT-proBNP, highly sensitive C-reactive protein (hsCRP), sST2, galectin-3, procollagen type I C-terminal propeptide (PICP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1).

Results. Volumetric parameters of the left ventricle (LV),LV mass indexed to growth and NT-proBNP were higher in the group of HFpEF patients (p<0,05 for all). The concentrations of galectin-3, PICP were higher, and the MMP-9/TIMP-1 ratio decreased in patients with T2D compared with the control group (p<0,05 for all). PICP values were higher in patients with HFmrEF compared with patients with HFpEF (106,4 (85,4; 140,4) ng/ml vs 46,8 (12,6; 98,6 ng/ml), respectively, p=0,043). In patients with T2D and HF, a relationship was found between TIMP-1 andLV end-diastolic volume (r=-0,68; p=0,042).

Conclusion. Patients with HFmrEF and T2D have higherLV volume and mass, higher concentrations of NT-proBNP and PICP in comparison with patients with HFpEF. The direction of MMP-9/TIMP-1 changes may reflect a decrease in antifibrotic processes. Further prospective studies on large samples using a multiple biomarker model are required in T2D and various HF phenotypes.

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.

Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.

Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na⁺ /K⁺ . Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.

Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.

Aim. To study clinical and hemodynamic and laboratory parameters for the 2-year prognosis of patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM).

Material and methods. The study included 90 patients (61,4±8,6 years old) with NYHA class II-IV CHF related to coronary artery disease and hypertension. All patients underwent clinical examination, resting 12-lead electrocardiography, transthoracic echocardiography, and blood chemistry testing. Two-year follow-up was conducted to determine the prognosis of patients with CHF and DM.

Results. CHF duration in patients with DM was 17% more, despite a comparable average age of patients. Echocardiography showed significant left ventricular dilatation and, as a result, systolic dysfunction in patients of the I group (with DM). Hypoalbuminemia was detected in both groups, but it was more pronounced in patients with CHF and DM. With comparable average creatinine concentrations, patients with CHF and DM had higher blood urea levels (13,2±2,1 µmol/L and 9,4±2,6 µmol/L, respectively). Patients of group I had significantly lower glomerular filtration rate (GFR) compared to the comparison group (by 13%). In group I, there were 42 rehospitalizations during the follow-up period, while in the comparison group — 29. Acute cerebrovascular accident was recorded in 7% and 4% of cases, respectively. Myocardial infarction (MI), including recurrent MI, was registered 50% more often in patients with DM. The mortality rate in patients of the group I was 3,5 times higher than in the comparison group.

Conclusion. Features of the course of CHF depending on the presence of concomitant type 2 DM were revealed. These include the relatively early manifestation of CHF symptoms, the prevalence of patients with moderate to severe CHF and severe left ventricular systolic dysfunction. The results of a biochemical study of the blood of group I patients were characterized by hypoalbuminemia, hypertriglyceridemia, and a significant decrease in GFR. It is noted that the presence of concomitant DM aggravates the course of CHF of ischemic and nonischemic genesis, which is manifested by an increase in the frequency of repeated hospitalizations and deaths during 2-year follow-up.

 

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Aim. To assess the effect of dapagliflozin in patients with heart failure with reduced ejection fraction (HFrEF) on reducing cardiovascular mortality as the main goal of a federal project on the prevention of cardiovascular diseases.

Material and methods. All adult Russian patients with a documented NYHA class II-IV HFrEF (EF £40%) were considered the target population. The characteristics of the patients corresponded to those of the Russian Hospital Heart Failure Registry (RUS-HFR). The study looked at an increase in the dapagliflozin use in addition to standard therapy by 10% of patients annually in 2021-2023 and calculated the number of deaths that could be prevented. Cardiovascular mortality curve was created by extrapolation of the DAPA-HF study results using the Kaplan-Meier method. Further, the contribution of prevented deaths with dapagliflozin to the achievement of regional and federal targets for reducing cardiovascular mortality was calculated for 1, 2, and 3 years.

Results. In case of 10% annual increase in dapagliflozin use in patients with NYHA class II-IV HFrEF, this will allow:

—   to prevent an additional 1,736 cardiovascular deaths in the first year, achieving the target of federal project on the prevention of cardiovascular diseases in 2021 by 5,9%;

—   to prevent an additional 3,784 cardiovascular deaths in the second year, achieving the target of federal project on the prevention of cardiovascular diseases in 2022 by 12,9%;

—   to prevent an additional 5,485 cardiovascular deaths in the third year, achieving the target of federal project on the prevention of cardiovascular diseases in 2023 by 18,7%.

Conclusion. The use of dapagliflozin in patients with HFrEF will reduce mortality from cardiovascular diseases.

The article presents the main results of the Russian post-marketing multicenter open-label program TRICOLOR (Triple fixed-dose combination in the treatment of hypertension).

Aim. To evaluate the antihypertensive efficacy and tolerability of the triple amlodipine/indapamide/perindopril fixed-dose combination, as well as the adherence of hypertensive (HTN) patients to this therapy in actual clinical practice.

Material and methods. The program enrolled 1247 outpatients aged 18 to 79 of both sexes with essential HTN. All patients included in the study receive amlodipine/ indapamide/perindopril fixed-dose combination. The patient’s condition was assessed according to four visits: visit 1 — at inclusion, visit 2 — after 2 weeks, visit 3 — after 4 weeks, visit 4 — after 12 weeks of follow-up. At each visit, the achievement of the target blood pressure (BP) <140/90 mm Hg and <130/80 mm Hg. At enrollment and visit 4, quality of life was analyzed using the SF-36 questionnaire and adherence to therapy using a validated 6-question questionnaire.

Results. After 12 weeks, a significant decrease in systolic and diastolic BP was recorded — by 33,5 and 14,3 mm Hg, respectively (p<0,001). Target BP <140/90 mm Hg after 12-week follow-up was achieved by the overwhelming majority (93,4%) of patients. After 12 weeks, the proportion of patients with good medical adherence increased from 18,8% to 49,0%, while the proportion of patients with low adherence, on the contrary, decreased from 46,3% to 5,1%.

Conclusion. The results of the TRICOLOR program demonstrate a high antihypertensive efficacy, good tolerance and medical adherence of triple amlodipine/indapamide/perindopril fixed-dose combination in patients with essential HTN in actual clinical practice in Russia.

The review article presents current data on the clinical and prognostic significance, as well as on the prevalence of comorbidities in patients with atrial fibrillation (AF). The prevalence of hypertension, diabetes and heart failure in patients with AF is discussed according to the Russian and foreign registry studies, randomized clinical trials. The problem of the effect of comorbidity on the risk of embolism and bleeding in AF is outlined. Potentialities of a novel oral anticoagulant edoxaban (based on the ENGAGE AF-TIMI 48 trial) for managing the risks of thromboembolic and bleeding events in AF and comorbidities. Sub-analyzes of the ENGAGE AF-TIMI 48 trial were discussed, which demonstrated efficacy comparable to warfarin in the embolism prevention and higher safety against bleeding, regardless of the comorbidity profile.

Recent multicenter studies using high-tech cardiac imaging and novel translational technologies have shown that cardiac fibrofatty replacement, characteristic of arrhythmogenic cardiomyopathy (ACM), is observed in both ventricles; left ventricular (LV) involvement may be minimal, on par with the right ventricle (RV), or dominant. In 2019, the Heart Rhythm Society (HRS) proposed a new approach to the assessment of arrhythmic and genetic diseases with the inclusion of new phenotypes — left-dominant ACM and biventricular ACM. In 2020, to improve the diagnosis of left ventricular phenotypes, European experts revised ACM criteria (based on the 2010 ITF criteria), which are called the Padua criteria.

The presented article highlights the clinical and genetic aspects of the new concept and the difficulties in ACM diagnosis, the practical experience of using new diagnostic algorithm. To help practitioners, step-by-step differential diagnosis and risk stratification of right and left ventricular phenotypes are presented using clinical examples (leftdominant ACM with a pathogenic variant in the LMNA gene; right-dominant ACM associated with a desmoplakin gene mutation, with predominant RV and moderate LV involvement; and an isolated RV ACM associated with a mutation in the plakophilin 2 gene).

Currently, the development of chronic heart failure (CHF) is considered from the perspective of pathological structural remodeling of myocardium and fibrosis. Despite the widespread use of molecular genetic markers in clinical practice, only a small number of them are used to evaluate remodeling processes, as well as to predict potential complications associated with heart failure (HF). In addition, the relationship between many biomarkers with instrumental and histological confirmation of myocardial fibrosis has not yet been determined. Myocardial fibrosis remains quite debatable and controversial subject, which actualizes the further study of this direction. The discovery of pathogenetic and diagnostic markers of myocardial fibrosis could contribute to the development of targeted therapy. Of particular interest is the search for possible pathogenetic markers, since this is relevant for clinical practice.

In cardiovascular studies, two related parameters that determine the same physical variable are often recorded. Interpretation of the calculated indicators presented in the form of ratios and differences is difficult, since they can be associated with several combinations of primary data giving the same value.

Aim. To find a way to overcome this limitation and take a more comprehensive approach.

Material and methods. We analyzed the data on left ventricular volume and blood pressure (BP) in 275 patients (women — 207), obtained using echocardiography and BP monitor. To calculate a lost companion (c) value based on a difference or dimensionless ratio, we applied the Pythagorean theorem. The lost companion is

defined as the hypotenuse in each study area. To calculate the pulse pressure companion (PP), the following formula was used: PP(c)=Ö(SBP²+SBP²). Similar methods were applied to ejection fraction (EF), augmentation pressure (AG) and AG/PP ratio, resulting in the ratio called augmentation index (AIx).

Results. 1. Mean blood pressure (MBP) acts as a surrogate for the PP companion (PPc) values (R=0,970, N=257). 2. We have identified correlations between PPc and pulse wave velocity (R=0,397, N=193), and AGc with AIx (75) (R=0,662, N=198). 3. EF has an inverse relationship with the end diastolic volume (EDV) (R=-0,559, N=187), and the ventricular-arterial coupling (VAC) correlates with ESV (r=-0,627, N=180). 4. Comparison of EDV and VACc revealed R of 0,949.

Conclusion. Companions calculated from the available data can have significant additional diagnostic value without the need for additional measurements. It is important to note that the combination of traditional ratio-based and suggested companions allows for more accurate data on individual patients.

According to modern healthcare requirements, it is necessary to increase workforce capacity of primary care practice, therefore, improving the specialist training is one of the high-priority problems of medical education. Not enough attention is paid to paramedic education and their role in Russian healthcare. The presented analysis of the paramedic profession history and the current state of high-quality healthcare in Russia shows the need to create a regulatory basis for the training of paramedics in the higher education system — a bachelor’s degree.

Aim. To assess the features of diagnosis, treatment and outcomes of pulmonary embolism (PE) in patients of Russian hospitals.

Material and methods. The register included all hospitalized patients with PE identified by any diagnostic method. Duration of inclusion was 12 months. In-hospital period management was assessed. Information about the included patients was provided by 20 hospitals from 15 Russian cities.

Results. For the period from April 15, 2018 to April 15, 2019, 609 patients were included in the register (women — 50,7%, mean age — 63,0±14,5 years, minimum-maximum — 19-94 years). Among the known risk factors for PE, the most common were lower limb varicose veins (31,4%), heart failure (23,3%), previous deep vein thrombosis (19,4%), cancer (17,1%). The median time from symptom onset to suspicion/confirmation of PE was 4 days (1-3 quartiles — 1-8 days). Shortness of breath, syncope/presyncope, chest pain/discomfort, cough, leg pain or lower extremity asymmetry and hemoptysis were noted in 88,7%, 30,0%, 29,8%, 17,3%, 9,4% and 8,5% of patients, respectively. Echocardiography was performed in 89,5%, and Doppler ultrasound of lower limb veins — in 85,9% of patients. Signs of venous thrombosis were found in 57,8% of patients. Computed tomographic (CT) pulmonary angiography was performed in 89,2% of patients, pulmonary scintigraphy and pulmonary angiography — 0,8% each.

Conclusion. Symptoms and main risk factors for PE in Russian patients did not fundamentally differ from those previously known. There was good adherence to modern guidelines for the diagnosis of PE, but adherence to guidelines on drug therapy met requirements only in half of the cases. There was an excessive use of TLT, as well as the use of ineffective methods of administering and monitoring anticoagulant therapy.In total, imaging technologies were used in 90,6% of patients, and signs confirming PE were found in 92,7%. Thrombolytic therapy (TLT) was performed in 25,0%; 92,0% of patients received anticoagulants. At the same time, unfractionated heparin (UFH) was injected subcutaneously in 26,3% of cases, and in one third of patients the drug was injected in doses unadjusted by body weight. In 42,7% of patients received UFH, the target activated partial thromboplastin time was not achieved. With warfarin treatment, the target international normalized ratio was achieved in only 48,4% of patients. Inferior vena cava filter placement and thrombectomy were performed in 1,3% each. During hospitalization (median — 11 days), 9,9% of patients died.

Aim. To study the prevalence of geriatric syndromes and assess their relationship with senile asthenia in persons aged ³65 years living in Russian regions with different demographic, climatic and socio-economic characteristics.

Material and methods. We examined 664 patients aged 65-107 years (mean age, 79±9 years; men, 25%) living in Moscow (n=365) and Voronezh (n=299). All patients underwent a comprehensive geriatric examination, which consisted of two stages: a survey with original questionnaire and an objective examination.

Results. The prevalence of senile asthenia was 66,4%, including 47,4% in people aged 65-74, 71,1% — 75-84 years, and 82,8% — ³85 years (p for trend <0,001). Senile asthenia was associated with age (odds ratio (OR), 2,36; 95% confidence interval (CI), 1,89-2,93; p<0,001) and female sex (OR, 1,52; 95% CI 1,06-2,18; p=0,024). Patients with senile asthenia had a lower socioeconomic status. Also, close associations of senile asthenia with other geriatric syndromes (dementia, depression, vision and hearing impairment, incontinence, falls, high risk of falls, functional decline, failure to thrive) with OR from 1,32 to 7,22 were revealed.

Conclusion. The first results of the EVCALIPT study indicate a high incidence of senile asthenia in persons aged ³65 years and its close association with other geriatric syndromes and socio-economic factors.

Aim. To compare the shortand medium-term outcomes of hemiarch and nonhemiarch replacement for ascending aortic aneurysm (AAA).

Material and methods. The study included 151 patients with non-syndromic AAA who underwent an elective replacement. Patients were divided into two groups: group 1 (non-hemiarch, n=40) — standard ascending aortic replacement; group 2 (hemiarch, n=111) — ascending aortic replacement with the hemiarch anastomosis in conditions of moderate hypothermia and circulatory arrest with unilateral antegrade cerebral perfusion. To eliminate systematic differences between the compared groups, the propensity score matching (PSM) method was used.

Results. Before PSM, there were no significant intergroup differences in the incidence of neurological complications, myocardial infarction, prolonged ventilation, or acute kidney injury. Bleeding-related reoperation rates and hospital mortality significantly differed between groups. After pseudo-randomization between the non-hemiarch and hemiarch groups, there were no significant differences in the incidence of neurological events, myocardial infarction, prolonged ventilation, reoperations for bleeding, acute renal injury, and hospital mortality. Median-term survival and freedom from aortic reoperations also did not show significant intergroup differences.

Conclusion. Hemiarch replacement for AAA does not lead to an increase in the incidence of postoperative complications, as well as the risk of shortand mediumterm mortality compared with non-hemiarch.

Aim. To create a methodological base for distance learning of cardiology healthcare professionals — multimedia clinical diagnostic tasks.

Material and methods. The interdisciplinary team used text and multimedia formats for clinical diagnostic data. Web technologies provided remote access to information located on the server.

Results. The report presents the experience of the practical implementation of multimedia clinical diagnostic tasks in cardiology, including the augmented reality. The variability of presenting information to students is implemented in the multimedia clinical diagnostic tasks, which is integrated with the rating system for evaluating decisions. The solution paths are determined by the actions of the students in the trigger interactive blocks and is evaluated by the rating system. Personal rating is a numerical value that integrally characterizes the decisionmaking competence of students. The conversion of the quantitative rating into the conventional form (‘pass/fail’, ‘excellent’, ‘good’, ‘passing grade’) will be provided after the trial period of the software.

Conclusion. The created Web service and computer simulations can become a methodological basis for the distance learning in cardiology. This technology can be in demand in the continuing medical education.

We report a case of mixed phenotype cardiomyopathy (non-compaction cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy), associated with DSP genetic variant.  The sudden cardiac death was the first and only symptom.

The article presents the results of clinical, instrumental and molecular genetic tests of three generations of a family with inherited cardiomyopathy caused by a new variant in the MYBPC3 gene. A specific feature of this case is the phenotypic heterogeneity of the mutation — a combination of hypertrophic cardiomyopathy and left ventricular non-compaction in family members. Attention is drawn to the various severity of clinical manifestations in relatives of carriers of mutation: from asymptomatic to severe heart failure and acute cerebrovascular accident.

In February 2020, apandemic of a SARS-CoV-2 infection was declared. The number of people who have been exposed to the novel coronavirus infection is steadily increasing around the world. Comparison of data on pathogenesis, clinical course, complications and outcomes with other respiratory viral infections, primarily caused by Betacoronavirus, gives reason to expect an increase in the number of patients after COVID-19 with long-term cardiovascular, respiratory and other complications. In the pathogenesis of possible complications, the leading role will be played by impaired immune function, primarily the adaptive immunity. This review examines the involvement of T-helpers and the humoral factors they produce in the pathogenesis of complications of viral (coronavirus) infections with cardiovascular and respiratory injury, as well as the known data on the genetic determination of cytokine-producing activity of these cells.

Extracellular vesicles are biological membrane-coated objects with size less then 1000 nm. They can contain variety of biologically active molecules (such as proteins, miRNA, mRNA, DNA etc.) and also are able to provide intercellular communications and implement lots if biological functions. Now possibilities of using extracellular vesicles for therapeutic approaches against various diseases and pathological conditions are rapidly discovered. In the most of cases mesenchymal stem cells are the sources of extracellular vesicles and miRNAs which vesicles transport are considered to be causable agents of their activities. In-vitro studies show that extracellular vesicles provide anti-inflammatory, anti-apoptotic activities and can stimulate angiogenesis and regeneration. Performed studies which were analyzed and structurized by us in this review demonstrate current perspectives for clinical use of extracellular vesicles in the therapy of such clinical conditions as oxidative stress, ischemia-reperfusion injury, tumor growth etc.

The role of molecular genetic factors in cardiovascular disease (CVD) development has been actively studied in recent years. In patients with acute myocardial infarction and heart failure, the genetic component contributes to the determination of inflammation and persistence of inflammatory mediators in the myocardium. The genetic component in combination with traditional CVD risk factors determines the clinical course of the disease, the severity and its outcome. This review summarizes the data on relationship of proand anti-inflammatory cytokines with coronary artery disease and its clinical manifestations.

Home blood pressure monitoring (HBPM) is strongly recommended by current guidelines as an effective out-of-office diagnostic and monitoring tool in patients with hypertension (HTN). However, there are personal, cultural, logistic difficulties owing to low effectiveness of HBPM. These put HBPM at a disadvantage in routine clinical practice. As such, telehealth solutions are of special interest nowadays, particularly blood pressure telemonitoring (BPTM) with or without remote counseling. BPTM might become something of digital assistant in the long-term patients’ follow-up and it fits well into the practice of continuity of medical care. The purpose of this review is to highlight not only the benefits of BPTM, but important discrepancies that may impede its widespread implementation in everyday clinical work. Critical comments address the lack of long-term, high-quality studies, absence of hard clinical outcomes and uncertainty on the best technical performance.