Aim. To identify the role of impaired production of hypoxia-inducible factors (HIF) 1 and 2 in determining the balance of angiogenesis mediators, pro- and antiinflammatory cytokines in peripheral and coronary sinus blood in patients with coronary artery disease (CAD), with and without ischemic cardiomyopathy (ICM).

Material and methods. The study included 30 patients with coronary artery disease (CAD) and non-cardiomyopathy, 22 patients with CAD without cardiomyopathy, and 20 healthy donors. Patients with non-cardiomyopathy had a lower left ventricular ejection fraction (LVEF) compared to CAD patients without cardiomyopathy (30,00 [22,00; 36,00]% and 59,50 [50,25; 67,00]%, p<0,001). Peripheral (cubital vein) and coronary sinus blood was used as the sample material. The plasma concentrations of TNF-α, TGF-β1, IL-10, VEGF-A, PDGF, and SCF were assessed in both blood samples using a multiplex assay, while HIF-1α, HIF-2α, and IL-6 — an enzyme-linked immunosorbent assay.

Results. In the peripheral blood of patients with CAD, regardless of ICM, the concentration of TNF-α, IL-6, VEGF-A, PDGF was normal, while the SCF level showed a tendency to increase (p=0,054), and TGF-β1 — to decrease (p=0,059); excess IL-10 and HIF-2α was determined only in patients with ICM (respectively, 2,80 [2,00; 3,30] pg/ml versus 1,78 [0,50; 2,40] pg/ml, p=0,018; 40,0% vs 0% of positive cases, p=0,047), excess HIF-1α — only in CAD patients without cardiomyopathy (6,00 [5,00; 6,20] ng/ml and 4,60 [3,28; 5,11] ng/ml, p=0,049). In the coronary flow relative to the peripheral flow in CAD patients without ICM, the concentration of TNF-α, IL-6, PDGF was higher (1,09 [0,68; 2,47] pg/ml, p=0,004; 5,85 [3,12; 7,15] pg/ml, p=0,011; 7,60 [3,70; 9,94] pg/ml, p=0,036), which was not determined in patients with ICM, who had a higher content of TGF-β1 (4,42 [3,38; 5,69] pg/ml, p=0,022). Regardless of ICM type, the VEGF-A content in sinus blood exceeded the systemic level (7,80 [3,25; 9,75] pg/ml, p=0,041), while the concentration of HIF-1α, IL-10, and SCF corresponded to them.

Conclusion. Insufficient cardiac angiogenesis in ICM is largely associated with the anergy of the myocardial proinflammatory response with atherogenesis, rather than with reduced response to hypoxia. This, on the contrary, is more significant at the systemic level in ICM pathogenesis and is characterized by the predominance of HIF-2 over HIF-1.

Cardiac amyloidosis, or amyloid cardiomyopathy, is an infiltrative disease leading to cardiac wall thickening, impaired left ventricular diastolic function, and arrhythmias, followed by the development and progression of heart failure. Ninety-five percent of amyloid cardiomyopathy is caused by two following types of amyloidosis: AL amyloidosis or ATTR amyloidosis. In clinical practice, the combination of these two types of amyloidosis is extremely rare, accounting for 0,8%. This case report demonstrates amyloid cardiomyopathy in a patient with 2A multiple myeloma (Ig-A kappa), AL amyloidosis, and genetically determined hereditary transthyretin amyloidosis (TTR mutation c.302C>, p.A101V). The paper describes the clinical performance, medical history, and diagnosis, and discusses specific amyloidosis therapy.

Aim. To conduct a cost-effectiveness analysis of implementing a specialized heart failure (HF) patient management system at the regional level.

Material and methods. The necessary costs for implementing a specialized HF patient management system in average region within the current healthcare system included staff salaries, training costs, and equipment costs for outpatient HF clinics, inpatient HF departments, and HF patient "schools". To assess the potential economic impact of implementing a specialized HF management system in the region, a mathematical HF model was proposed. This model assumed (1) the absence of such a system in the region, (2) current treatment consistent with the PRIORITY-HF study data, and (3) achievement of optimal HF therapy (a combination of an angiotensin receptor-neprilysin inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist, and a sodium-glucose cotransporter-2 inhibitor) in all patients based on the implementation of the specialized heart failure management system. The potential HF population in the region was calculated per 100 000 residents.

Results. Taking into account standards for cardiologist workload and HF prevalence, one outpatient HF center/office for every 400 000 residents should be established. The amount of additional funding required to expand the implementation of specialized HF patient management systems per 100 000 people (based on the costs of equipment, salaries, and training in the first year and salaries in subsequent years) is RUB 1,6 million for the first year, RUB 4,3 million over 3 years, and RUB 13,7 million over the 10-year analysis (i.e., an average of RUB 1,4 million per year). We demonstrated that, by improving the efficiency of patient management, specialized heart failure patient monitoring systems become economically feasible already within the first year of implementation. The overall reduction in budget expenditures, taking into account the costs of implementing specialized HF patient management systems, amounted to RUB 5,5 million, or RUB -3,128 per 1 HF patient subject to monitoring. Moreover, over 10 years of implementation, 827 deaths and 678 hospitalizations due to heart failure will be prevented per 100 000 people, while budget savings (taking into account cost savings on hospitalizations and deaths in patients with HF with a lower probability of disease progression) will amount to RUB 5,5 million in the first year, RUB 13,9 million over 3 years, and RUB 22,9 million over 10 years over the analysis.

Conclusion. The implementation of specialized HF patient management systems may represent an optimal strategy for reducing the burden of disease both in terms of the clinical effectiveness of treatment and economic feasibility.

Mineralocorticoid receptors (MRs) play a significant role in the pathogenesis of a number of internal diseases, including heart failure, hypertension, and chronic kidney disease. Their excessive activation contributes to the development of inflammation, fibrosis, tissue remodeling, and the development of cardiovacular-kidney-metabolic syndrome. The effectiveness of MR antagonism in promoting cardiac and renal protection has been confirmed by large experimental and clinical studies. However, there are significant differences in pharmacological properties between steroidal and nonsteroidal MR antagonists.

This article presents the characteristics of MR antagonists registered in the Russian Federation, including their clinical effects, safety profile, and indications for use. Particular attention is paid to the drug selection algorithm, taking into account individual patient characteristics and the balance of potential benefits and risks. The material is based on current European and Russian clinical guidelines and is intended for practical use by internists in the management of patients with cardiovascular and renal diseases.

The expert consensus proposes a potential program of action to address the problem of low medication adherence in asymptomatic chronic diseases. The experts recognize adherence as a key factor in the success of chronic disease treatment and consider improving adherence as one of the strategic objectives of all programs to reduce mortality and the overall burden of chronic diseases.

This consensus provides valuable advice on the clinical management of patients and the interpretation of research data in areas not covered by clinical guidelines. It is intended for neurologists, cardiologists, and general practitioners. It combines data from modern studies on the risk of cognitive impairment and stroke in patients with lipid metabolism disorders. Approaches and algorithms for hypertriglyceridemia correction as part of the primary and secondary prevention of diseases associated with cerebrovascular diseases and atherosclerosis were developed.

This review analyzes current studies on the stability of various blood biochemical parameters, including those used in routine clinical and research pracice, during processing and long-term storage of blood derivative samples in biobanks. The installation of biobanks, as divisions of research and clinical centers that ensure standardization and quality of pre-laboratory research, is becoming a global trend and serves as an effective tool for improving the quality of biomedical research. The following main preanalytical factors affecting the stability of analytes are discussed: delayed centrifugation, storage temperature and duration, and freeze-thaw cycles of biospecimens. A wide variety of indicators, both variable and stable, were described for various violations of the preanalytical stage of laboratory testing. The quantification of one or more preanalytical biomarkers appears to be a reliable and valid method for the assessment of the processing and storage of blood samples and their derivatives. This is of particular relevance when seeking to confirm the quality of samples for specific types of research. The most appropriate approach to assessing the quality of biobank samples, from both economic and technical perspectives, is the use of routine biomarkers determined in clinical diagnostic laboratories. Candidate markers for violations of fundamental preanalytical procedures for working with biosamples and optimal modes of sample preparation and storage have been proposed, which are most likely not to have a critical impact on the stability of most biochemical blood parameters.

This review addresses the problem of resistance to antiplatelet therapy (acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor), which increases the risk of thrombosis, myocardial infarction, and stroke in cardiac patients. The causes of this phenomenon are complex and include genetic, metabolic, and inflammatory factors. The key focus of this review is the application of modern proteomic technologies for an in-depth study of molecular mechanisms of resistance. High-resolution mass spectrometry and isotope labeling enable the identification and quantification of thousands of proteins in platelets, revealing specific proteomic signatures associated with impaired therapy response. This review summarizes the results of studies demonstrating changes in the platelet proteome both with response and resistance to antiplatelet therapy. A proteomic approach has identified specific protein biomarkers associated with antiplatelet therapy resistance, such as THBS2, DECR1 for acetylsalicylic acid, and SPON2, galectin-9 for clopidogrel, which are involved in platelet activation, inflammation, and metabolism. Proteomic analysis paves the way for personalized medicine, offering the basis for new diagnostic tests and strategies for overcoming resistance.

Aim. To assess the myocardium inotropic reserve in patients with chronic coronary artery disease (CAD) with preserved and reduced left ventricular ejection fraction (LVEF) in β1- and β2-adrenoreceptor (AR) stimulation, and the need for inotropic support after surgical treatment of CAD.

Material and methods. Inotropic responses of isolated myocardial trabeculae to β1- and β2-AR stimulation were studied in 16 patients with preserved LVEF and 17 patients with reduced LVEF. The inotropic response of trabeculae was assessed in isometric mode. Agonists were used to effect β1- and β2-AR against the background of preliminary α-AR block. All patients underwent coronary artery bypass grafting. Vasoactive inotropic score (VIS) in the postoperative period was calculated.

Results. Adrenergic activity of trabeculae in patients with preserved LVEF is provided by β1-AR, and in patients with reduced LVEF — by β2-AR, which is 150 (138; 163)% and 139 (120; 193)%, respectively. In this case, the total β-adrenergic reactivity of the trabeculae with reduced LVEF is lower than with preserved LVEF (p=0,034). VIS in reduced LVEF exceeded the threshold values and was three times higher than with preserved LVEF (p=0,007).

Conclusion. In chronic CAD, the myocardium retains pronounced β-adrenergic reactivity. With preserved LVEF, the main contribution to myocardial β-adrenergic reactivity is made by β1-AR. With reduced LVEF, β-adrenergic reactivity is determined by β2-AR, but this does not completely compensate inotropic effects. This fact may probably be one of the reasons for greater need for postoperative inotropic support in patients with reduced LVEF.

Aim. To assess the contribution of aortic valve (AV) calcification severity to permanent pacemaker (PP) insertion after transcatheter aortic valve implantation (TAVI) during the hospitalization.

Material and methods. The study included 94 patients with severe aortic stenosis who underwent TAVI. All patients underwent multislice computed tomography (CT) before the procedure to assess AV calcification.

Results. During the hospital period, eight patients (8,5%) required PP implantation. CT made it possible to reveal that patients who underwent pacemaker implantation after TAVI compared with patients without pacemaker had higher calcium volume in the left coronary cusp (LCC) (424,6 mm³ [223,1-524,7] vs 151,6 mm³ [91,9-276,2], respectively, p=0,005) and non-coronary cusp (608,2 mm³ [254,5-805,2] vs 283,7 mm³ [173,6-398,9], respectively, p=0,035). As a result of multivariate regression analysis, the independent predictors of pacemaker implantation after TAVI were the initial right bundle branch block (RBBB) (odds ratio (OR): 15,77; 95% confidence interval (CI): 2,06-120,5; p=0,008) and LCC calcium volume >300 mm³ (OR: 7,98; 95% CI: 1,38-46,11; p=0,020).

Conclusion. According to the study results, initial RBBB and LCC calcification are independent predictors of permanent pacemaker implantation after TAVI during the hospital period. Further studies are needed to predict and prevent post-operative complications.

Aim. To analyze the effect of elevated high-sensitivity C-reactive protein (hs-CRP) on the clinical course and complexity of coronary artery disease (CAD), and the risk of coronary artery bypass graft (CABG) failure.

Material and methods. The study included 84 patients with stable CAD who underwent examination and isolated CABG. Evaluation of hs-CRP levels was performed before surgery, 24 hours and 7 days after CABG. Control coronary bypass angiography was performed intraoperatively and 1 year after CABG.

Results. We found that chronic increase in hs-CRP levels affects the complexity of CAD (Syntax Score) and the development of critical unfavorable prognostic coronary lesions. The risk of hemodynamically significant stenosis of the left coronary artery trunk increases 6-fold (odds ratio 5,9; 95% confidence interval (CI): 1,89-18,5). Dysfunction of coronary conduits was determined in 12% of patients 1 year after CABG, which was caused by thrombotic vein graft occlusion in 70% and hemodynamically significant graft stenosis in 30% of cases. These patients had significantly higher hs-CRP levels at all testing time points (before surgery, 24 hours and 7 days after CABG), indicating a more pronounced activation of inflammatory mechanisms. Predictive analysis established a significant role of hs-CRP levels before surgery (relative risk (RR) 1,43; 95% CI: 1,23-1,67, p<0,001) and 24 hours after surgery (RR 1,16; 95% CI: 1,06-1,27, p<0,001) as a risk factor for coronary bypass graft failure in the midterm period after surgery.

Conclusion. Our study confirmed the leading role of inflammation in triggering and maintaining the main mechanisms determining coronary conduit damage after CABG, which is the basis for bypass graft failure. Established elevated hs-CRP levels can be considered as predictors of bypass graft failure and unfavorable outcomes of myocardial revascularization.

Russian Society of Cardiology (RSC)

With the participation of: the Association of Cardiovascular Surgeons, All-Russian Scientific Society of Specialists in Clinical Electrophysiology, Arrhythmology and Pacing (VNOA)

Approved by the Research and Practical Council of the Ministry of Health of the Russian Federation.

Russian Society of Cardiology (RSC)

With the participation of: the Association of Cardiovascular Surgeons, All-Russian Scientific Society of Specialists in Clinical Electrophysiology, Arrhythmology and Pacing (VNOA)

Approved by the Research and Practical Council of the Ministry of Health of the Russian Federation

Russian Society of Cardiology (RSC)

With the participation of: All-Russian Scientific Society of Specialists in Clinical Electrophysiology, Arrhythmology and Pacing (VNOA), Association of Pediatric Cardiologists of Russia, Russian Society of Holter Monitoring and Noninvasive Electrophysiology, All-Russian Public Organization "Russian Society of Emergency Medical Care"

Approved by the Research and Practical Council of the Ministry of Health of the Russian Federation