Aim. To determine the pathogenetic role of the oxytocinergic system in the development of myocardium structural and functional changes in women with heart failure with preserved ejection fraction (HFpEF) associated with type 2 diabetes mellitus (DM2T) (diabetic phenotype of HFpEF).

Material and methods. The study included 60 women aged 67.0±4.9 years with HFpEF stage I-IIA, FC I-III, 30 of them had DM2T who were admitted for elective coronary artery bypass grafting. The development of HFpEF is caused by coronary artery disease (CAD) and arterial hypertension (AH). Prior to surgery, all patients underwent a standard examination, blood levels of NT-proBNP, oxytocin (Ox), echocardiography were determined to find the types of left ventricular (LV) myocardial remodeling and diastolic dysfunction (DD). Myocardium biopsies of the right atrium auricle obtained during coronary bypass surgery were studied by microscopy, morphometry and immunohistochemistry (the expression of oxytocin receptors (OxR), a marker of proliferation ki-67).

Results. According to echocardiography, eccentric LV hypertrophy (46.7/36.7%) and DD type 2 (47/17%, p=0.003) prevailed in the group of women with the diabetic phenotype of HFpEF. A higher content of NT-proBNP (480.72±241.87/434.46±282.78 ng/ml, p=0.06) and a lower concentration of Ox (102.11±35.89/320.37±294.71 pg/ml, p=0.0016) in blood serum were established, as well as an increase in the number of cardiomyocytes (CMC) with a high expression level OxR (63.69±19.47/12.16±23.09%, p=0.000) in patients with the diabetic phenotype of HFpEF. Negative associations were determined between the blood level of Ox and the CMC diameter (r=-0.10, p=0.020), the area of their cytoplasm (r=-0.16, p=0.000) and the area of the nuclei (r=-0.11, p=0.015) in patients of both groups. A decrease in Ox concentration in the blood of patients with diabetic phenotype of HFpEF was accompanied by an increase in the number of CMCs with a high level of OxR expression (r=-0.63, p=0.000).

Conclusion. The study has shown the important involvement of oxytocinergic signaling pathways in the HFpEF pathogenesis. HFpEF associated with DM2T in women was characterized by more unfavorable structural and functional changes in the myocardium, a significant increase in the number of hypertrophied CMCs with a high level of OxR expression and Ox decrease in blood serum. The mechanisms of the first-established significant increase in the content of Ox in the blood of patients with HFpEF without diabetes and its significant decrease in patients with diabetic phenotype of HFpEF leading to more pronounced structural and functional changes in the myocardium, require further study.

Aim. To investigate the state of the platelet and plasma components of hemostasis in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).

Material and methods. The study included 42 patients with non-ST-segment elevation myocardial infarction (NSTEMI): MINOCA (n=24) and MI-CAD (n=18). Platelet aggregation ability in response to activation was evaluated using Solar AP2110 and LASCA aggregometers. Platelet functional activity and calcium signaling were assessed using flow cytometry methods. The plasma component of hemostasis, in addition to routine coagulation tests was evaluated using the global coagulation test "Thrombodynamics". The control groups for tests consisted of healthy volunteers.

Results. When analyzing the ability of platelets to form aggregates by the aggregometry tests, it was found that platelets in the MINOCA group formed aggregates significantly worse upon ADP stimulation at various concentrations compared to the MI-CAD group. However, when platelets were stimulated with collagen, the opposite effect was observed: in the MI-CAD group, there was a noticeable decrease in aggregate formation in terms of light scattering amplitude compared to the MINOCA group. Flow cytometry using the functional platelet activity test protocol revealed that both groups showed a significantly increased platelet size after activation, reduced platelet granularity) both at rest and upon activation, significantly decreased number of procoagulant phosphatidylserine-positive platelets, and reduced dense granule release upon activation compared to healthy volunteers. The calcium signaling test showed a weakened calcium release in response to ADP in the MINOCA group compared to the MI-CAD group. In the study of the plasma component, no significant differences between the groups or deviations were found according to both routine tests and the "Thrombodynamics" test.

Conclusion. Platelet activity did not differ significantly between the MINOCA and MI-CAD groups; however, in the MINOCA group, platelet activity was lower in some tests compared to the MI-CAD group. In the study of the plasma hemostasis component, normocoagulation was recorded in both groups.

Aim. To assess the compliance of nephroprotective and anticoagulant therapy in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) with modern clinical guidelines.

Material and methods. The study included patients with CKD in combination with AF and in sinus rhythm. Clinical characteristics were retrospectively assessed, as were the use of renin-angiotensin system inhibitors (RASi), statins, sodium-glucose transporter type 2 inhibitors (SGLT-2i) and oral anticoagulants (OAC).

Results. A total of 464 patients (aged 66-80 years) were divided retrospectively in two subgroups — with and without AF. AF was detected in 210 (45.3%) patients. Patients from the subgroup with AF were significantly older (75 vs 72 years, p=0.001), more often had type 2 diabetes mellitus (T2DM) (28.6% vs 20.5%, p=0.042), coronary artery disease (CAD) (40.5% vs 30.7%, p=0.028) and chronic heart failure (CHF). (57.6% vs 22.8%, p<0.001). Mean estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was lower (46 vs 51 ml/min/1.73 m², p<0.001) in patients with AF compared with the group without AF. ACE inhibitors (ACEi) were prescribed in 127 cases (27.4%), angiotensin II receptor blockers (ARBs) — in 227 (49%), angiotensin receptor neprilysin inhibitor (ARNI) — 33 (7.1%), statins — 362 (78%), SGLT2i — 63 (13.6%), direct oral anticoagulants (DOACs) — 203 (43.8%) and warfarin — in 10 cases (2.2%). In those patients in whom SGLT2i was prescribed, eGFR according to the CKD-EPI equation was significantly lower (47 vs 49 ml/min/1.73 m², p=0.043). In patients with T2DM, SGLT-2i-2 was prescribed in 33.9% of cases, in patients with chronic heart failure with reduced ejection fraction (CHFrEF) — in 68.4% of cases. In 196 patients with AF, DOACs were prescribed, in 10 cases — warfarin.

Conclusion. Most patients with CKD receive nephroprotective therapy with RASi and statins according to current KDIGO guidelines. A significant proportion of patients with CHFrEF receive SGLT-2i, but only a third of patients with T2DM and CKD received SGLT-2i therapy.

Aim. To assess the incidence of chronic myocarditis in patients with atrial fibrillation.

Material and methods. The study included 145 patients. The majority of patients were male — 118 (81.4%). The median age was 45 (38; 50) years. Most had paroxysmal AF — 60 (41.4%), slightly fewer had persistent AF — 55 (37.9%), 30 (20.7%) patients had long-term persistent AF. All patients underwent radiofrequency ablation of AF and endomyocardial biopsy (EMB) with subsequent histological and immunohistochemical studies (IHC). Morphological verification of myocarditis was performed in accordance with the Dallas criteria modified by the World Heart Federation.

Results. Signs of chronic myocarditis were identified in 64 patients (44.1%). The median age of patients with myocarditis was 44 (36.5;49) years, without myocarditis — 46 (38;51) years. In men, myocarditis was detected in 50 cases (42%), in women — in 14 (51.9%). In paroxysmal AF, myocarditis was detected in 25 patients (41.7%), in persistent AF — in 23 (41.8%), and in long-term persistent AF — in 16 (53.3%). The groups with and without chronic myocarditis were comparable when compared based on the main echocardiographic parameters. Regression analysis did not show a significant influence of these factors on the probability of detecting chronic myocarditis in patients with AF. In patients under 30 years of age, there were no signs of inflammation without the presence of myocardial fibrosis, while the maximum stage of fibrosis occurred in patients from 31 to 40 years of age. The stage of fibrosis did not depend on gender. More often than others, a combination of enterovirus and herpes virus type 6 was detected in biopsy specimens. In patients over 51 years of age, biopsies generally did not express any virus on immunohistochemical studies.

Conclusion. Chronic myocarditis in patients with AF was significantly more often detected in younger patients (up to 50 years inclusive), and was more common in women, as well as in the presence of a long-term persistent form of AF, regardless of gender. Detection of myocardial fibrosis signs is more typical for young patients with the maximum stage at the age of 31 to 40 years.

Aim. Using the CHAID (Chi Squared Automatic Interaction Detection) method to develop a classification tree for predicting hospital mortality in patients with non-ST-elevation myocardial infarction (non-STEMI) aged 75 years and older and compare the quality of the constructed model with the logistic regression model.

Material and methods. A retrospective analysis of the case histories of 119 sequentially enrolled patients aged ≥75 years who were hospitalized in a cardiology department due to non-STEMI in 2020-2021 was carried out. The construction of a predictive model of probability of dying was carried out using the logistic regression method. To assess the impact of various predictors affecting the probability of dying during the of hospitalization period in patients with non-STEMI, a classification tree was developed using the CHAID method. To compare the quality of logistic regression models and the classification tree, the areas under the ROC curve and confidence intervals were estimated.

Results. Based on the construction of a binary logistic regression, it was found that the factors increasing hospital mortality were cardiogenic shock (CS): odds ratio (OR) 47.55; 4.00-589.16; p=0.002; new-onset atrial fibrillation: OR 6.45; 1.39-30.42; p=0.018; and the number of points on the GRACE scale: for each increase by 1 point: OR 1.03; 1,00-1,05; p=0.046. Similar data were obtained when analyzing the classification tree: in patients with CS, the predicted mortality was 91.7%. The probability of an unfavorable outcome based on the constructed classification tree was higher than the average in the analyzed sample in persons without CS, 2-3 degree atrioventricular blocks, and pulmonary edema, but with right bundle branch block on the electrocardiogram (25.0%) and in persons without CS and atrioventricular blockages of 2-3 degrees, but with pulmonary edema and a Q wave on the electrocardiogram (50.0%). Both methods of predicting hospital mortality are applicable. There were no statistically significant differences in the quality of both constructed models; the difference in the areas under the ROC curves was 0.043±0.268 with a 95% confidence interval of -0.055-0.141, p=0.387.

Conclusion. Both developed methods can be used to determine the probability of dying in a hospital. Currently, the recruitment of patients into a prospective study of a similar design has begun and is continuing, during which validation of the constructed forecasting models is planned.

Aim. To establish the frequency of achieving target of blood pressure (BP) levels and lipid spectrum parameters (LS) in patients with arterial hypertension (AH) and multifocal atherosclerotic lesion (MFAL) with normal and elevated levels of lipoprotein (a) (Lp(a)) in real clinical practice.

Material and methods. The study included 110 patients with AH and MFAL, median age was 59.0 (51.0; 64.3) years. Depending on the level of Lp(a), all patients were divided into 2 groups: group 1 — 72 patients (65.5%), Lp(a) level was ≤50 mg/dl (13.2 (3.7; 21.1)), group 2 — 38 patients (34.5%) Lp(a) level was >50 mg/dl (89.5 (62.5; 110.0)). The diagnosis of MFAL included damage to two or more arterial basins according to carotid artery, abdominal aorta and lower extremities arteries duplex scan. Patients of both groups received antihypertensive, lipid-lowering, and antiplatelet therapy.

Results. Patients in groups 1 and 2 showed similar blood pressure levels and frequency of antihypertensive therapy use. In both groups, the majority of patients were on a free combination of antihypertensive drugs, only a third of patients used a fixed combination. In most cases, patients of both groups did not reach the target blood pressure levels (63.9% — group 1, 55.3% — group 2), despite the fact that the average blood pressure figures were relatively low (132;83 mmHg in each group). Drug control was also unsatisfactory in both groups, regardless of the level of Lp(a). However, all drug indicators were significantly worse in group 2, despite comparable lipid-lowering therapy, which more often included statin monotherapy. Combination therapy with lipid-lowering drugs was used in patients of groups 1 and 2 only in 20.8% and 10.5%, respectively. Parameters of low-grade inflammation high-sensitivity C-reactive protein and interleukin-6 did not differ between the groups and did not exceed the reference values.

Conclusion. An increased level of Lp(a) may be accompanied by drug disorders and increased BP in patients with MFAL. Due to the lack of effective Lp(a) reducing therapy, the prevention of cardiovascular events in such patients should focus on BP and lipid spectrum correction. The use of fixed combinations, including antihypertensive and lipid-lowering drugs, can lead to improved adherence to therapy, increased BP and LS control.

The article defines the original drug (OD) and examines the history of the appearance of generic drugs (GD), as well as the evolution of views to prove their bioequivalence to OD. The question is considered to what extent pharmacokinetic equivalence can guarantee the clinical equivalence of OD and GD. The data on the rules of registration of GD in different countries are provided. A brief overview of various types of studies comparing the clinical efficacy and safety of OD and GD (meta-analyses, randomized controlled trials, observational studies, description of clinical cases) and their main results is given. The results of a number of observational studies on the replacement of OD with GD and its consequences are presented. The existing system of current quality control of GD is described, numerous cases of recall of GD due to detected violations during their production are given. It is mentioned about individual cases of clinical inefficiency of GD and their side effects identified by the practical physicians. It is concluded that a qualitatively produced GD with proven pharmacokinetic equivalence to OD is able to provide therapy of the same quality as OD. However, numerous cases of the appearance of GD on the pharmaceutical market, which does not correspond to the quality of OD, make us somewhat wary of therapy based on VP. Both the practitioner and the patient should know which of the drugs prescribed by the international nonproprietary name is OD and which is GD.

The article briefly describes the stages of creating the main methods of acute myocardial infarction (MI) and its complications treatment. It is noted that currently existing clinical guidelines (CG) were formed at the end of the first decade of the XXI century; since then there have been no principal changes in the CG due to the lack of fundamentally new approaches to the acute MI treatment, its immediate and long-term outcomes. Compliance with the current CG has significantly reduced hospital mortality in acute MI and improved long-term outcomes. However, today, despite compliance with the CG, the absolute hospital mortality rates for acute MI remain quite high, and the long-term prognosis of patients’ lives is very unfavorable. A number of major randomized clinical trials that ended in 2023-2024 and studied fundamentally new approaches to the treatment of acute MI and its long–term outcomes are analyzed. It is noted that none of these studies gave a positive result. A new study with beta-blockers, which proved its positive effect on the mortality of patients with acute MI in the 80s of the twentieth century, gave negative results. This may indicate that a number of acute MI treatment methods, the effectiveness of which was proven several decades ago, have now lost their significance. It is concluded that despite compliance with modern CG, the residual risk of death after acute MI remains quite high. It is necessary to develop principally new methods of treating this disease.

Resistant arterial hypertension is characterized by failure to control target blood pressure despite long-term use of optimal or maximum tolerated doses of three different antihypertensive drugs, including diuretic. Patients with resistant hypertension are included in a group of people at high risk of cardiovascular and renal complications, including accelerated progression of chronic kidney disease with a more rapid transition to the final stage of the disease. Resistant hypertension is based on a salt-sensitive, volume-dependent form of hypertension, which usually occurs against the background of increased aldosterone production and normal or even decreased renin plasma activity. A key role in its formation is played by an increase of sodium reabsorption in the kidneys, associated with excessive activity of aldosterone-sensitive epithelial sodium channels (ENaC), which control the reabsorption of this ion in the distal segments of the nephron. Its assumed that in this pathological process, in addition to aldosterone, is also involved the small Rho GTFase Rac1 — regulatory G-protein, which can enter into a direct ligand-independent interaction with mineralcorticoid receptors, performing the function of a powerful nonsteroidal activator of the transmission of their intracellular signals. Based on controlled, randomized clinical trials, the optimal fourth drug to overcome resistance in such patients is the steroid mineralcorticoid receptor antagonist spironolactone. However, the inclusion of this drug in antihypertensive therapy not only fails to control blood pressure in a significant proportion of patients with resistant hypertension, but also significantly increases the risk of hyperkalemia, especially in people with impaired renal function. The review presents data on the pharmacodynamics and pharmacokinetics of new inhibitors of aldosterone synthase-aldosterone-mineralocorticoid receptor hormonal system baxdrostat and finerenone, as well as the results of clinical studies assessing the clinical effectiveness and safety profile of these drugs in patients with resistant hypertension.

The Beers Criteria are a tool for optimizing pharmacotherapy in elderly patients, containing information on potentially inappropriate drugs, which is only advisory in nature and is not mandatory for use in Russian Federation. In the updated version of the Beers Criteria from 2023, the expert opinion on rivaroxaban has changed — instead of "use with caution", as stated in the previous document from 2019, the experts now believe that "long-term treatment with rivaroxaban in non-valvular atrial fibrillation (AF) and venous thromboembolic complications (VTE) should be avoided in favor of safer alternative anticoagulants". This statement is based on moderate-quality evidence obtained from observational studies and network meta-analyses, which are significantly inferior to randomized controlled trials and have numerous limitations. The available evidence base for the use of rivaroxaban in elderly patients with AF and VTE and critical comments on the Beers criteria methodology, indicate the recommendations of the American Geriatrics Society experts regarding direct oral anticoagulants (DOAC) should be treated thoughtfully and carefully. When choosing a DOAC in elderly patients with AF or VTE, one should primarily focus on current clinical guidelines mandatory for use in Russian Federation, and on the data of studies that studied the efficacy and safety of specific DOACs in this category of patients. Rivaroxaban is a well-studied anticoagulant in elderly patients with AF and VTE, since its efficacy and safety have been established in RCTs and specially designed multicenter prospective observational studies with a fairly high quality of evidence. Based on this, rivaroxaban is a justified treatment option for elderly and senile patients with AF or VTE.

Cardiology, like other branches of medicine, is increasingly faced with the need not only to optimize patient treatment, reduce financial costs, but also to improve long-term outcomes. The volume of information required for such tasks is significant, and a doctor’s time is severely limited. Additional software capable of processing large amounts of data in a short period can assist doctors. Clinical decision support system (CDSS) is a type of software that, based on numerous clinical characteristics, provides doctors with information on the most likely diagnosis, patient risk profile, most suitable therapy, and more. Nowadays, CDSS finding more and more applications in cardiology and cardiovascular medicine. The experience of its clinical use has also been accumulated in the Russian Federation. The problem of the correct choice of anticoagulant therapy remains relevant in clinical practice. In addition, despite the proven benefit of prescribing anticoagulants in patients with atrial fibrillation (AF) at a high risk, the frequency of "underprescription" of oral anticoagulants (OACs) remains relatively high. The introduction of a strategy for a personalized approach to the selection of anticoagulants, based on individual patient characteristics, can significantly improve adherence to clinical guidelines and, as a result, reduce the risk of thromboembolic complications. This article discusses the positive and negative aspects of using CDSS in the management of patients with AF, highlighting the main limitations when using them in conditions close to real clinical practice.

The article describes a clinical case of BRAHH syndrome in a patient with arterial hypertension and permanent atrial fibrillation (AF). The patient took perindopril 10 mg, indapamide 2.5 mg, amlodipine 10 mg, bisoprolol 2.5-5 mg daily. She was admitted to a hospital complaining of severe weakness, a heart rate decreases to 38 beats per minute against the background of high blood pressure. During the examination, she was diagnosed with complete atrioventricular block against the background of AF, stage 4 chronic kidney disease and severe hyperkalemia (potassium 8.7 mmol/l). The patient was prescribed treatment aimed at eliminating hyperkalemia, and temporary pacing was established. Against this background, her condition improved, and the complete atrioventricular blockade was resolved. This clinical example meets the criteria of BRAHH syndrome, since against the background of taking an atrioventricular node blocker in a small dose, a patient with chronic kidney disease and severe hyperkalemia developed complete atrioventricular block against the background of AF, accompanied by high blood pressure.

The article presents a clinical case of development of mural infective endocarditis (IE) with formation of vegetations in the region of the upper third of the interventricular septum in patient A., 51 years old, with uncorrected tetralogy of Fallot. The patient was admitted with complaints of increased heart rate, interruptions in the heart work, feet swelling, shins up to the upper third, dyspnea at rest, general weakness, fever up to 39 ^оC, sweating, headache. During transthoracic echocardiography on the upper third of the interventricular septum (IVS) from the side of the RV, an additional echo-positive linear mobile formation 0.9 cm long is visualized, similar to the chords of the tricuspid valve. Thus, based on the identification of 1 major Duke criterion (imaging criterion — the presence of parietal vegetation) and 3 minor criteria (predisposing factors — congenital heart disease of the blue type; fever >38 ^оC; positive blood culture not meeting the requirements for the major criterion), laboratory and instrumental diagnostic data and anamnesis, the following diagnosis was established: "Secondary infective endocarditis with damage to the upper third of the interventricular septum". Taking into account the sensitivity of the identified microflora, polymyxin and moxifloxacin were prescribed. During therapy, a dry cough and dry wheezing in the projection of the middle lobe on the right appeared. To exclude septic embologenic pneumonia, computed tomography of the chest organs was performed, on which no focal/infiltrative changes were detected. However, a shunt connecting the brachiocephalic trunk with the right pulmonary artery was visualized, which may explain the cause of compensation of hypoxemia that arose due to pathological hemodynamics as a result of high pulmonary stenosis. Given the incomplete effectiveness of therapy, as well as the sensitivity of the infectious agents isolated, a decision was made to change antibacterial therapy to vancomycin in combination with imipenem. Conservative treatment methods allowed not only to compensate for the existing clinical symptoms, but also to achieve reference values of laboratory parameters, despite the impossibility of surgical intervention.