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Aim. To study the long-term effects of complex therapy with the addition of enhanced external counterpulsation (EECP) in patients with stable coronary artery disease (CAD) complicated by chronic heart failure (CHF).Material and methods. In the open randomized trial EXCEL (NCT05913778), 118 Patients with the verified ischemic CHF NYHA class II-III with reduced or intermediate left ventricular ejection fraction were included. They were randomized into group 1 (n=59) — optimal medical therapy (OMT) and EECP (35 hours, 2 courses per year), group 2 (n=59) — OMT and EECP (35 hours, 1 course per year). The primary endpoint was the proportion of patients with a 6-minute walk test (6MWT) increase of at least 20% from baseline. The secondary composite endpoint included adverse cardiovascular clinical outcomes (myocardial infarction, revascularization, stroke, death), new cases of atrial fibrillation, diabetes mellitus, decreased renal function, and hospitalizations for CHF.Results. The average CHF NYHA class decreased in group 1 from 2.41±0.49 initially to 1.95±0.47 after 24 months (p20% (primary endpoint) in groups 1 and 2 after 24 months was 98.3% (n=58) and 79.7% (n= 46) respectively (p20%) — 16.4 times lower (odds ratio 0.061, 95% confidence interval 0.008-0.484; p=0.009).Conclusion. Over the 24-month study period, the effect of EECP in patients with coronary artery disease complicated by CHF demonstrated a stable improvement in exercise tolerance, as well as a decrease in the incidence of adverse clinical outcomes, significantly more pronounced in the group with a large number of EECP procedures

Aim. To study the effect of various therapy regimens with enhanced external counterpulsation (EECP) on exercise tolerance, quality of life, indices of structural and functional state of cardiovascular system in patients with stable coronary artery disease (CAD) complicated by chronic heart failure (CHF).Material and methods. The study included patients with stable CAD complicated by CHF with reduced and intermediate left ventricular ejection fraction (LVEF) from the randomized EXCEL trial (NCT05913778; n=120) and additionally patients with similar inclusion and exclusion criteria (n=90) who were randomized into groups with different EECP treatment regimens for 12 months: Group 1 (n=40): course of 35 hour-long procedures; Group 2 (n=40): course of 35 hourlong procedures every 6 months; Group 3 (n=30): course of 20 hour-long procedures then constantly 1 hour per week; Group 4 (n=30): constantly 2 hours per week; Group 5 (n=30): course of 20 hour-long procedures then constantly 2 hours per week; Group 0 (placebo ; n=40): course of 35 hour-long procedures with compression pressure 80 mm Hg. All patients at baseline and after 12 months were assessed for clinical status, quality of life (MLHFQ, SF-36), NT-proBNP levels, LVEF, as well as exercise tolerance (6-minute walk test; 6MWT) initially, after 3, 6, 9 and 12 months. Correlation analysis and risk assessment of adverse events (combined endpoint — combination of cases of adverse cardiovascular events, deaths, hospitalizations for CHF, new-onset of atrial fibrillation, diabetes, decreased renal function) was performed.Results. Treatment effectiveness had positive correlation with EECP duration (r(S)=0,670; p20% after 12 months was 7,7%, 72,5%, 97,5%, 76,7%, 90%, 100%, respectively. Cumulative event-free survival was highest in groups 5, 4, and 2 (0,97, 0,93, and 0,86, respectively), and the risk of developing combined endpoint in these groups was minimal (0,035, 0,075, and 0,150, respectively).Conclusion. The effect of EECP treatment in patients with coronary artery disease complicated by CHF depended on the EECP hours and regimen. Alternative EECP regimens (with more treatments spread evenly over the year) in addition to optimal medical therapy may improve the management of these patients.

Aim. To study the changes of the levels of cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (hsTnI)) in patients with newly diagnosed multiple myeloma (MM) during programmatic treatment with bortezomib (VCd regimen).Material and methods. This prospective pilot study included patients with a newly diagnosed MM (n=30), who were scheduled for a cycle of chemotherapy including a proteasome inhibitor (bortezomib). All patients underwent standard laboratory (complete blood count, biochemical tests, serum protein electrophoresis), electrocardiography, echocardiography, as well as the level of specific laboratory markers of myocardial dysfunction (NT-proBNP) and injury (hsTnI) was determined immediately before treatment, after 3 and 6 cycles of chemotherapy.Results. The mean age was 63,8±10 years with a slight predominance of men (56,7%, n=17). The patients initially had an increased level of NT-proBNP (316 [75,9; 602,6] pg/mL) with its decrease to 144,0 [102,3; 294,0] pg/ml after 3 cycles and to 109,2 [59,9; 344,5] pg/ml after 6 cycles of chemotherapy. At the MM onset, the mean hsTnI values were 0,06 [0,03; 0,49] ng/mL, whereas after 3 and 6 chemotherapy cycles it accounted for 0,02 [0,01-0,68] and 0,65 [0,02; 1,51] ng/ml, respectively, with the normal range of less than 0,1 ng/ml. Despite this, no statistical significance has been obtained. There were no clinical and/or laboratory signs of heart failure, ischemia, or other non-cardiac causes of elevated NT-proBNP levels in this cohort. Multivariate regression analysis revealed the following significant factors influencing the initial hsTnI level: paraprotein, hemoglobin and erythrocyte sedimentation rate (ESR). The resulting regression model was characterized by a strong correlation (r=0,702, p

Aim. To study the levels of pro-inflammatory biomarkers in patients with obstructive and non-obstructive coronary artery disease (CAD), to identify possible differences for diagnosing the degree of coronary obstruction.Material and methods. The observational study included two groups of patients: with non-obstructive (main group, coronary artery stenosis

Aim. To study the levels of fibrosis markers in patients with stable coronary artery disease (CAD) and various types of coronary artery (CA) lesions (obstructive and non-obstructive), to identify possible differences for diagnosing the types of coronary obstruction.Material and methods. The observational study included three groups of patients: with non-obstructive (main group, coronary artery stenosis 0.05). There were no statistically significant differences in TGF-β1 levels depending on the type of left ventricular remodeling (p=0.139). The maximum level of MMP-9 was in the group with obstructive coronary disease and significantly differed from the main group (p

Neuregulin-1β (NRG-1) is an emerging biomarker of heart failure (HF). The mechanisms of its action in HF patients are yet to be investigated. Cardioprotective and anti-inflammatory effects of NRG-1 have been reported.Aim. To assess NRG-1 levels in HF patients and investigate the association between NRG-1 and biomarkers of inflammation and myocardial fibrosis.Material and Methods. NRG-1, biomarkers of inflammation and fibrosis (hsCRP, IL-6, sVCAM-1, MMP-9, Galectin-3, ST2, TGF-β) were assessed in 47 patients with HF and preserved ejection fraction (HFpEF); 39 patients with HF and reduced ejection (HFrEF) and 40 healthy participants. The associations between NRG-1 and biomarkers of inflammation and fibrosis, as well as the composite outcomes of cardiovascular death and HF hospitalisations were assessed.Results. Median NRG-1 levels in HFpEF were 0.969 (0.348; 1.932) ng/ml, in HFrEF – 0.63 (0.348; 1.932), in healthy participants 0.379 (0.195; 0.861) ng/ml, and was significantly higher in HFpEF compared to healthy volunteers (р=0.004). There was no difference in NRG-1 concentration between HFpEF and HFrEF. In HF patients, all biomarkers of inflammation and fibrosis were higher than in controls. ST2, IL-6 and TGF-β were significantly higher in HFrEF compared to HFpEF patients, while hsCRP, sVCAM-1, MMP-9, and Galectin-3 levels were comparable. In HFpEF, NRG-1 was associated with hsCRP (rs=0.378, p=0.023) and IL-6 (rs=0.378, p=0.014). Median follow-up time in patients with HFpEF and in patients was 312 (236; 388) days, in HFrEF – 147 (98; 237) days. In HFpEF, 2 patients died and 19 were hospitalized due to HF. In HFrEF, 10 deaths and 19 hospitalizations were registered. Kaplan-Mayer analysis showed that HFpEF patients with increased NRG-1 and IL-6 had higher levels of HF hospitalisation (log rank test, р=0.046 and р=0.012, respectively). In a multivariable cox proportional hazard model, the association between the NRG-1 and outcomes remained significant after adjustment for age, gender and NTproBNP but diminished when hsCRP and IL-6 were included in the model.Conclusion. NGR-1 level significantly higher in HFpEF compared to healthy participants, and comparable with NRG-1 concentrations in HFrEF. In HFpEF, NRG-1 was associated with biomarkers of inflammation and fibrosis. The prognostic value of NRG-1 in HF requires further investigations.

Aim. To assess the structure and performance of left atrium (LA) before and after 3 cycles of anticancer treatment in lymphoma patients, as well as the incidences of supraventricular arrhythmia (SVA) and the levels of biomarkers of inflammation.Material and Methods. This is a prospective observational study of patients with confirmed diagnosis of lymphoma [n=23; 57% men; median age 52 (34;64) years], who had no prior polychemotherapy. The comparison group included persons without lymphoma [n=18; 50% men; median age 43 (37; 54) years] comparable with the main group in terms of sex, age and risk factors for cardiovascular diseases. Patients with lymphoma underwent 24h-ECG monitoring and advanced transthoracic echocardiography at baseline and after 3 cycles (within 3 months) of anticancer treatment. Biomarkers of inflammation were measured. The results were compared with the data of the comparison group.Results. In lymphoma patients, LA reservoir, conduit, and booster function were found to be impaired at baseline but were comparable with these in matched controls. After 3 cycles of anticancer treatment, a trend to reduction of LA booster and conduit strain was found. The proportion of those with SVA was significantly higher in lymphoma patients before chemotherapy compared to those after anti-cancer treatment or controls: 57% vs 10% and 33% respectively (p

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p

Aim. To study the effect of enhanced external counterpulsation (EECP) on the functional status, quality of life, structural and functional state of the vascular bed, and markers of glycemic control in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM).Material and methods. A pilot prospective randomized study included 30 patients with CAD and DM. Using a random number generator, patients were randomized into 2 groups: EECP (n=15) and a comparison group (n=15). All patients (n=30) received optimal medical therapy (OMT) during 3 months of follow-up. Patients in the EECP group underwent a course of EECP (35 hours, cuff pressure: 220-280 mmHg) during the first 7 weeks of the study. At baseline and after 3 months of follow-up, patients in both groups underwent an assessment of clinical status, quality of life (based on the SF-36 questionnaire), as well as a 6-minute walk test to assess exercise tolerance. The dynamics of fasting glucose, postprandial glucose, insulin resistance index (HOMA-IR) and glycated hemoglobin were assessed. Photoplethysmography and applanation tonometry were performed to assess the state of the vascular bed.Results. In the EECP group, after 3 months, there was a decrease in the frequency of angina attacks and an improvement in the functional class of angina according to the Canadian Cardiovascular Society (CCS) classification. A significant improvement in exercise tolerance was revealed [an increase in the 6-minute walking distance by 51 (35; 65) m, p0.05), with the exception of the reflection index and the stiffness index (p

Aim. To determine the median levels of neuregulin-1 (NRG-1; endothelium-derived growth factor and the natural agonist of the ERBB3 and ERBB4 receptors) NRG-1 in healthy volunteers and to study the associations of NRG-1 levels with gender and age.Material and Methods. Ninety seven healthy participants were enrolled (median age of 44 [32-54], men 45 men [46.4%]). The following age groups were identified: 20-29 y.о. (n=20, men – 50.0%), 30-39 y.о. (n=21, men – 52.4%), 40-49 y.о. (n=22, men – 45.5%), 50-59 y.о. (n=22, men – 36.4%); 60-69 y.о. (n=12, men – 50.0%). Peripheral blood samples were collected at the time of enrolment, standard laboratory tests were performed, and NRG-1 levels were determined in the plasma samples by ELISA.Results. In the cohort of 97 healthy participants the median value of NRG-1 was 0.3 [0.121-2.24] ng/ml. NRG-1 levels did not differ significantly between men and women (p=0.145), indicating that NRG-1 levels are not influenced by gender. The levels of NRG-1 were similar in the different age groups: age 20-29 years=0.26 [0.17-0.37] ng/ml; age 30-39=0.24 [0.1-0.39] ng/ml; age 40-49=0.31 [0.19-1.15] ng/ml; age 50-59=0.37 [0.19-1.0] ng/ml; age 60-69=0.4 [0.13-0.81] ng/ml. Correlation analysis between NRG-1 levels and route blood measurements (haemoglobin, lipids, glucose, creatinine, and uretic acid) did not show significant associations.Conclusions. In this study, the median value of NRG-1 plasma levels were determined. The results of the study show that age and gender had no influence on NRG-1 values.

Aim. To study the mid-term effects of enhanced external counterpulsation (EECP) in the structural and functional parameters of blood vessels, exercise tolerance and quality of life indicators in patients with verified coronary artery disease (CAD).Material and methods. Patients (n=70) with verified stable CAD (angina pectoris class II-III) complicated by chronic heart faillure class II-III (NYHA) were included in the study. Data from 65 patients (48 to 74 years old; 45 men and 20 women) are included in the final analysis. All patients had a course of EECP (35 hours procedures with a compression pressure of 220-280 mm Hg). All patients at baseline, 3 and 6 months later had a 6 walk minute test (6WMT), an assessment of the clinical status, quality of life of patients (Minnesota Living with Heart Failure Questionnaire, SF-36). Computer nailfold video capillaroscopy, photoplethysmography with pulse wave recording and contour analysis, applanation tonometry to assess central aortic systolic pressure and radial augmentation index were performed to assess the structural and functional state of large and microcirculatory vessels.Results. Significant improvement in exercise tolerance both after 3 and after 6 months (increase in distance in 6WMT by 44.6% after 3 months and 34.3% after 6 months, p

Aim. To study the level of serum biomarkers of endothelial dysfunction and myocardial stress in patients with various types of hypertrophic cardiomyopathy (HCM).Material and Methods. 48 patients with hypertrophic cardiomyopathy (27 men and 21 women) were examined, the mean age was 54±13 years. The patients were divided into two groups according to the course options: group 1 - symptomatic stable course (n=14); group 2 - progressive course of symptomatic HCM (n=34). In accordance with the assigned tasks, all patients underwent determination of biological markers of neurohumoral systems in blood serum using immunofluorescence assay analysis: N-terminal fragment of brain natriuretic peptide (NT-proBNP), von Willebrand factor (vWF), endothelin-1, E-selectin with subsequent evaluation and correlation of results with clinical and instrumental characteristics of patients. When performing echocardiography following parameters were assessed: dimensions of the heart chambers, the thickness of the interventricular septum, the thickness of the posterior wall of the left ventricle (LV), LV mass, LV mass index, the ratio between LV filling in diastole (peak E) and atrial systole (peak A)-(E/A), relative myocardial thickness index, left atrial volume index.Results. Both groups showed increased levels of NT-proBNP and endothelin-1. E-selectin and vonWillebrand factor remained within the normal range. There was no statistically significant intergroup difference. There was a correlation between the level of the index of the relative myocardial thickness and the level of NT-proBNP (r=0.30; p=0.04). A correlation was found between the level of the vWF marker and the left atrial volume index (r=0.32; p=0.04). When assessing the association of indicators of intracardiac hemodynamics with other markers (E-selectin and endothelin-1, no statistically significant relationships were found.Conclusion. In the course of the research, it was found that the high activity of endothelin-1 and NT-proBNP reflects endothelial dysfunction and myocardial stress in patients with HCM, especially in patients with a progressive variant of HCM. However, we did not find any changes in the levels of E-selectin and von Willebrand factor, as well as their intergroup differences. These results require additional studies to assess endothelial dysfunction in patients with HCM.

Heart failure with preserved ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Little progress has been in the treatment of this condition since its introduction some 30 years ago. It's accepted that HFpEF is heterogeneous in many ways, ethologically and phenotypically. The underlying mechanisms of the syndrome are not clear. Recently, it has been shown that the diagnostic criteria for HFpEF lacks sensitivity and specificity. Novel treatment approaches, which were developed based on current HFpEF pathophysiological concepts, did not show either clinical or prognostic benefit for patients. Therefore, there is an urgent need to revise current diagnostic approaches and to further investigate the underlying mechanisms. Recently, two novel diagnostic score systems were proposed: H2PEF and HFA-PEFF. Recently, a number of phase II and III randomized control trials have been completed. Here, the authors discuss the potential novel diagnostic approaches to HFpEF and treatment perspectives.

The prevalence of coronary heart disease (CHD) and type 2 diabetes mellitus (type 2 diabetes) in Russia and in the world continues to increase. Despite the prevention and optimization of therapy, CHD retains its leadership among all causes of death, and the mortality rate from type 2 diabetes and its complications gradually increases too. To improve the treatment of the above mentioned diseases, it is necessary to clarify the pathogenetic mechanisms of their development. The formation of endothelial dysfunction, characterized by an increase in the level of cell adhesion molecules and vasoconstriction, is a common link characteristic for the course and progression of CHD and type 2 diabetes. This article presents an analysis of preand clinical studies on the role of endothelial dysfunction markers: cell adhesion molecules (E-selectin), vasoconstriction (endothelin-1) and von Willebrand factor in patients with CHD, including those with type 2 diabetes mellitus.

Aim. To study some vascular remodeling markers in hypertensive patients depending on the presence of type 2 diabetes mellitus.Material and methods. The study included patients with essential hypertension 1-2 degrees of increase in blood pressure with/without type 2 diabetes (30 and 32 patients respectively). Using photoplethysmography in combination with reactive hyperemia test structural and functional markers of vascular remodeling were determined: in large vessels – stiffness index and phase shift; in microvessels – reflection index and the occlusion index. Using the computer video capillaroscopy of the nail bed the density of the capillary network at rest, after venous occlusion and after the test with reactive hyperemia was determined. ELISA was used for determining the level of humoral markers of endothelium dysfunction and vascular bed remodeling: metalloproteinase 9, metalloproteinase 9 inhibitor, E-selectin, endothelin, transforming growth factor (TGF-β1), endothelial growthfactor A.Results. In compare with hypertensive patients in hypertensive patients with type 2 diabetes significantly higher stiffness index values (11.15 [10.05; 12.35] vs 10.15 [8.83; 11.83] m/s; p=0.04) were found as well as significantly lower (p=0.00) capillary network density at rest (26.4 [24.2; 27.6] vs 35.1 [33.0; 45.0] cap/mm2; p=0.00) after the tests with reactive hyperemia (29 [24; 33.3] vs 40.0 [35.0;43.3] cap/mm2; p=0.00) and venous occlusion (32.5 [27.8; 34.5] vs 40.0 [33.0; 45.0] cap/mm2). In hypertensive patients with type 2 diabetes significantly higher levels of TFG-β1 (11648 [4117.8; 37933.8] vs 3938.5 [1808.8; 7694] pg/ml; p=0.00) and significantly lower levels of endothelin-1 (0,46 [0,29;1,3] vs 1.73 [0.63; 2.30] ng/ml; p=0.01) was detected in compare with hypertensive patients without type 2 diabetes.Conclusion. In both groups some signs of vascular remodeling were found at the level of both large arteries and microvessels (arterioles and capillaries). However, the group of hypertension + type 2 diabetes mellitus had statistically significantly more pronounced changes in arterial stiffness, capillary network density, as well as humoral markers levels of fibrosis and endothelial dysfunction.

Obesity is one of the leading and the most serious risk factors of cardiovascular diseases. Overweight provokes many metabolic and hemodynamic disorders. About 30% of inhabitants of the planet have overweight and prevalence of obesity increases by 10% every 10 years according to the WHO data. The probability of arterial hypertension in obese patients is 50% higher than in people with normal body mass. Framingham study showed that obesity is an independent, significant risk factor of ischemic heart disease, myocardial infarction, cerebral stroke and diabetes mellitus. The most dangerous is the central obesity with the preferential fat deposition in the abdomen. Combination of visceral obesity, violation of carbohydrate and lipid metabolism, arterial hypertension, and close pathogenic relationship between these factors underlie the isolated symptom complex known as metabolic syndrome. J. Vague was the first to describe relationship between abdominal obesity with cardiovascular disease and mortality in 1947. In our country G.F. Lang noticed common combination of arterial hypertension with obesity, lipid and carbohydrate metabolism disorders. Thus, metabolic syndrome significantly increases risk and severity of cardiovascular disease. Within last decades criteria of metabolic syndrome stays constant. The factors of insulin resistance and endothelial dysfunction as stages of the pathogenesis of the metabolic syndrome have been studied in detail. The mechanisms of insulin resistance and endothelial dysfunction are discussed in detail in this article as well as inflammatory markers and the significance of highly sensitive C-reactive protein.

Possibilities and prospects for the clinical use of enhanced external counterpulsation (EECP), which has long established itself throughout the world, are discussed in the article. Historical background, as well as the development stages of EECP for the treatment of patients with coronary heart disease (CHD) and chronic heart failure (CHF) are considered. The mechanism of action of the EECP and the main hemodynamic, neurohumoral and tissue effects that justify its use are presented. The effect of EECP on endothelial function and coronary reserve, disorders of which occurs in the majority of cardiovascular diseases, is considered separately. Treatment of patients with CHD, including complicated by CHF, are the most studied indications for EECP using in medical practice. The evidence base for treatment of patients with these disorders by EECP is presented in the article. Prospects for the EECP application in other areas of medicine are also presented.

Aim. To study the structure of co-morbidities, especially connective tissue undifferentiated dysplasia syndrome (CTDS), in patients with hypertrophic cardiomyopathy (HCM) to develop an algorithm of complex examination of patients.Material and methods. Patients with HCM (n=186; 88 men and 78 women) were examined. The diagnosis of HCM was based on current guidelines; molecular genetic study was performed in the absence of phenotypic manifestations. Echocardiography and standard examination of cardiac patient were performed in all patients to identify comorbidities. Genotyping of polymorphisms of 12 modifying genes was performed in 61 patients and 61 people in the control group.Results. HCM was most often associated with uterine myoma (52%), cardiac and extracardiac congenital malformations (50%), and thyroid diseases (37%). Combination of HCM with different variants of connective tissue dysplasia was found in 17% of patients (mitral valve prolapse – 6.3%, tricuspid valve prolapse – 2.7%, supplemental chords – 4.5%, bivalve aortic disease – 1.8%, increased left ventricular trabeculation – 3.6%, atrial septal aneurysm – 3.6%, membranous ventricular septal defect – 1.8%).Conclusion. CTDS is one of the most often associated disorders in patients with HCM. The study of the association of CTDS and HCM, the nature of their genetic structure and similarity of pathogenesis require further study.