Aim . To study the long-term effect of enhanced external counterpulsation (EECP) therapy on exercise tolerance, quality of life (QoL), and indicators of the structural and functional state of the cardiovascular system in patients with stable ischemic heart disease (IHD) complicated by chronic heart failure (CHF). Material and methods . This open randomized EXCEL study included 120 patients with verified IHD complicated by NYHA II-III functional class CHF with reduced or mid-range left ventricular (LV) ejection fraction. Patients were randomized into group 1 (n=40), optimal drug therapy (ODT) and EECP (35 hours, 2 courses per year); group 2 (n=40), ODT and EECP (35 hours, 1 course per year); and group 3 (control; n=40), ODT and placebo counterpulsation (35 h, 1 course per year). All patients underwent a 6-minute walk test (6MWT), evaluation of clinical status, QoL with the MLHFQ and SF-36 questionnaires, structural and functional state of large blood vessels and microvasculature, measurement of brain natriuretic peptide precursor (NT-proBNP), and echocardiography at baseline and after 12 months. Results . In groups 1 and 2 after 12 months, the 6MWT distance increased statistically significantly (44.5 and 24.9%, respectively) and the following indexes improved: QoL (SF-36, MLHFQ), the condition of large blood vessels (phase shift, radial augmentation index, central aortic systolic pressure (CASP)) and microvasculature (occlusion index, percentage of perfused capillaries, percentage of capillary recovery), and the LV systolic function (from 40.6±7.5 to 47.5±10.2% and from 41.3± 6.8 to 43.9±10.3%, respectively). The proportion of patients with a >20% increase in the 6MWT at 12 months was 97.5, 72.5, and 7.7%, respectively. A statistically significant decrease in NT-proBNP was observed in all groups. In group 3, the incidence of hospitalizations for CHF and the risk of the composite endpoint were significantly higher. Conclusion . For the 12-month study period, the effects of EECP in patients with IHD complicated by CHF included improvements in exercise tolerance, QoL, vascular and cardiac functional parameters, and a decrease in the incidence of adverse outcomes.

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 <0.05), improved quality of life (increased overall score on the SF-36 questionnaire from 50.3±8.1 to 59.8±8.8, p<0.05), an increase in the left ventricular ejection fraction were found. Significant improvement in indicators showing the function of the endothelium of both large vessels (phase shift: from 5.6 [2.45; 7.3] to 6.8 [3.1; 8.1] m / s) and microcirculatory vessels (occlusion index: from 1.51 [1.21; 1.7] to 1.66 [1.2; 1.9]), as well as a decrease in functional disorders of the capillary bed of the skin (% of perfused capillaries, density of the capillary network in the test with reactive hyperemia) were found after 3 months. However, after 6 months, there were no significant changes in these parameters compared to the baseline value. No significant change in indicators showing structural remodeling of both large vessels and microcirculatory vessels was found.Conclusion. The positive effect of the EECP course on the functional status (exercise tolerance) and quality of life in patients with stable coronary artery disease complicated by chronic heart faillure was found both after 3 and 6 months. Positive dynamics of the functional state of large vessels and microvasculature was found only after 3 months.

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; p<0,001) and treatment regimen (r(S)=0,620; 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 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<0.05). There was also a significant decrease in the HOMA-IR [-9.9% (-26.5; -4.0) vs 7.7% (-7.9; 13.8), p=0.004], as well as in the levels of fasting glucose [-10.5% (-15.8; -4.0) vs -2.7 (-8.3; 5.9), p=0.012] in the EECP group, compared with the OMT group.Conclusion. EECP course therapy in addition to OMT has a positive effect on the functional status and quality of life of patients with CAD and DM. After 3 months of observation, there was noted a positive dynamics of the vascular state, as well as markers of glycemic control, and these changes were more pronounced in the EECP group. The results obtained may indicate the effectiveness of EECP as an add-on treatment for this group of patients.

Aim        A comprehensive assessment of retinal microcirculation in patients with stable ischemic heart disease (IHD) exhibiting obstructive and non-obstructive coronary artery (CA) lesions. Materials and methods This observational comparative study included 35 patients with stable IHD, divided into those with CA obstructive lesions (n=25) and those with ischemia with non-obstructive coronary arteries (INOCA) (n=10). A control group consisted of 30 healthy volunteers with no cardiovascular risk factors. The groups were matched for age and body mass index. All participants underwent coronary angiography or CT coronary angiography. Tissue perfusion and the amplitude-frequency spectrum of blood flow fluctuations (endothelial component) were assessed via laser Doppler flowmetry (LDF) of the bulbar conjunctiva, and optical coherence tomography angiography (OCT-A) of the macular region was performed using the SOLIX platform (Optovue, USA). Results Compared to the control group, patients with INOCA exhibited significantly higher vascular resistance (σ) and coefficient of variation (Kv), indicating more pronounced perfusion fluctuations. Both obstructive IHD and INOCA groups showed reduced endothelial flow amplitudes, a marker of endothelial dysfunction. OCT-A revealed that while macular vessel density remained stable, all IHD patients had increased foveal avascular zone (FAZ) area and perimeter. Specifically, the FAZ area was more significantly enlarged in obstructive IHD, whereas the FAZ perimeter was greater in INOCA ( p <0.05). The left eye FAZ perimeter showed moderate diagnostic accuracy in differentiating stable IHD patients from healthy volunteers (AUC=0.632). Conclusion LDF of the bulbar conjunctiva effectively captures systemic vascular alterations in IHD and differentiates between obstructive and non-obstructive IHD. The integration of LDF and OCT-A provides a promising multimodal approach for the early detection of microvascular impairment, including in IHD patients.

The development of different phenotypes of coronary artery (CA) lesions is regulated via many various factors, such as pro-inflammatory agents, zinc-dependent endopeptidases, growth factors and circulating microRNAs (miRs). To evaluate the expression levels of miR-34a, miR-145 and miR-222, tumor necrosis factor α (TNF-α), matrix metalloproteinases (MMP-1, -9, -13 and -14) and vascular endothelial growth factor (VEGF) in patients with different phenotypes of coronary artery disease (CAD): ischemia/angina with non-obstructive coronary arteries (INOCA/ANOCA) and obstructive CAD (oCAD) compared with a control group. This cross-sectional observational study included 157 subjects with a verified CAD diagnosis (51 patients with INOCA, 76 patients with oCAD and 30 healthy volunteers). The expression of miR-34a, miR-145 and miR-222 (RT-PCR) and the levels of VEGF, TNF-α, MMP-1, MMP-9, MMP-13 and MMP-14 (ELISA) were estimated in plasma samples. A higher concentration of MMP-9 was found in oCAD-group samples compared to the INOCA/ANOCA group. The INOCA/ANOCA group was characterized by higher levels of TNF-α. Based on multivariate regression analysis, a mathematical model predicting the type of CA lesion was constructed. MiR-145 was the independent predictor of INOCA/ANOCA (p = 0.006). Changes in concentrations of MMP-9 and MMP-14 were found in both investigated CAD groups, with MMP-9 levels being significantly higher in obstructive CAD samples than in INOCA/ANOCA, which confirms the role of inflammation in the development of atherosclerosis. A multivariate regression analysis allowed us to achieve a model that can predict the phenotype of stable CAD, and MiR-145 can be assumed as an independent predictor of INOCA/ANOCA.