Aim. Study of the association of polymorphic variants of CYP2C19 (G681A), P2RY12 (H1/H2), ITGB3 (T1565C), ITGA2 (C807T), eNOS3 (T786C) genes with high residual platelet reactivity (HRPR) to clopidogrel and acetylsalicylic acid (ASA) at different terms of myocardial infarction (MI).

Material and methods. The study included 400 patients with MI aged 31-74 years, 317 (79,3%) men and 83 (20,7%) women. Platelet aggregation performed on days 1-2, 12-14 and 28-30 of MI, and genotyping by the polymerase chain reaction were analyzed using the STATISTICA 10.0 program.

Results. Differences were found in ADP-test 1-3 depending on the CYP2C19 (G681A) polymorphism, ADP-test 1 depending on the P2RY12 (H1/H2) polymorphism, ADP-test 2 depending on the ITGB3 (T1565C) polymorphism, ASPI-test 1 depending on the eNOS (T786C) polymorphism. The risk of HRPR to clopidogrel is higher in 681A CYP2C19 allele carriers compared to the G681 carriers throughout the entire observation period: initially odds ratio (OR) of 1,8 (1,14-2,88), p=0,012, on days 12-14 of MI, OR of 1,7 (1,08-2,68), p=0,023 and on days 28-30 of MI, OR of 2,3 (1,42-3,81), p=0,0008. The risk of HRPR to clopidogrel is higher in AA CYP2C19 genotype carriers compared to GG genotype carriers, on days 1-2 of MI (OR 6,5 (1,16-36,4), p=0,033), on days 28-30 of MI (OR 7,8 (1,26-48,0), p=0,027). The risk of HRPR to clopidogrel on days 1-2 of MI is higher in H2 P2RY12 locus carriers compared to H1 locus carriers (OR 1,5 (1,02-2,22), p=0,039). The risk of HRPR to ASA on days 1-2 of MI is higher in the 786C eNOS3 allele carriers compared to T786 allele carriers (OR 1,4 (1,02-1,96), p=0,036). Carriers of haplotypes of minor alleles of CYP2C19 + ITGA2 + P2RY12 + eNOS genes (OR 3,9 (1,13-13,65), p=0,032) and CYP2C19 + ITGA2 + eNOS genes (OR 5,1 (1,7214,96), p=0,0032) have higher risk of HRPR to dual antiplatelet therapy (DAPT) on days 28-30 of MI compared to the rest of patients.

Conclusion. The association of HRPR to clopidogrel with the CYP2C19 (G681A) polymorphism was found during the entire observation period, with the P2RY12 (H1/H2) polymorphism on days 1-2 of MI, with the ITGB3 (T1565C) polymorphism on days 10-12 of MI. The association of HRPR to ASA with eNOS (T786C) polymorphism was found on days 1-2 of MI. Minor allele haplotypes of the CYP2C19 + ITGA2 + P2RY12 + eNOS genes and CYP2C19 + ITGA2 + eNOS genes were associated with a higher risk of developing HRPR to DAPT on days 28-30 of MI.

Aim. Branched-chain amino acids (BCAAs) have been postulated as potential indicators of cardiovascular risk. The objective of this study was to explore the relationship between plasma BCAAs and different stages of cardiovascular disorders.

Material and methods. In our cross-sectional study, plasma BCAAs (valine, leucine and isoleucine) in individuals without cardiovascular diseases (CVDs) (nonCVD group, total n=27, with n=16 healthy, but with metabolic disorders) were compared to patients diagnosed with CVDs [CVD group, total n=109, being n=61 hypertension (n=31 with signs of beginning of myocardial remodeling) and n=48 patients with coronary artery disease (CAD)].

Results. The plasma concentration of BCAAs was significantly higher in the group of patients with cardiovascular disease compared with the healthy group (p<0.05 for all amino acids tested): valine concentration was 238.7 [219.6; 267.0] μM in the non-CVD group and 261.2 [233.8; 298.7] μM in the CVD group; leucine concentration was 134.8 [122.4; 153.2] μM and 146.8 [129.0; 166.6] μM, respectively; and isoleucine 72.7 [65.3; 84.4] μM and 81.7 [68.0; 96.2] μM, respectively. Leucine and isoleucine concentration levels were minimal in the healthy participant subgroup and maximal in the IBS patient subgroup. No statistically significant differences in BCAAs concentrations were found in the subgroups without CAD. Significant increases in concentrations were observed in the subgroups of patients with CAD as follows: valine concentration was 256.3 [219.0; 297.9] μM in hypertension group and 261.7 [236.5; 307.5] μM in CAD group; leucine concentration was 141.8 [123.5; 166.6] μM and 154.1 [134.7; 172.7] μM, respectively, and isoleucine 72.8 [65.7; 94.0] μM and 85.7 [74.9; 101.7] μM, respectively. BCAAs profiles in all participants with metabolic disorders had “good” diagnostic accuracy with area under the receiver operating characteristics curve being 0.72, 0.70 and 0.70 for valine, leucine and isoleucine, respectively.

Conclusion. BCAAs concentrations are elevated with higher severity of the cardiovascular disorder and exhibit potential as early independent indicators of coronary artery disease.

A clinical observation of the treatment non-compliance consequences with clinical guidelines and principles of empirical therapy selection in a female patient with intravenous drug abuse, viral hepatitis C and HIV infection, with a history of a COVID-19 and the development of uncontrolled staphylococcal infective endocarditis (IE) of the tricuspid valve, complicated recurrence of early prosthetic IE is presented. Successful treatment was achieved only by a combination of tricuspid valve replacement and the appointment of etiotropic therapy for S. aureus (MSSA). The typical clinical scenario was not accompanied by the choice of adequate empirical antibiotic therapy, despite the high suspicion of association with MSSA, which determined the complicated course of IE. Only the polymerase chain reaction of the heart valve tissue played a key role in the etiological diagnosis. The use of valve tissue polymerase chain reaction in addition to traditional microbiological methods is a valuable diagnostic study.

The question of the safety of direct oral anticoagulants (DOACs), despite their high efficacy in the prevention of thrombotic events in atrial fibrillation (AF), remains relevant due to the risk of developing hemorrhagic events while taking standard doses, which requires a thorough personalized approach. The article presents a clinical case of the development of spontaneous hematomas on the skin of the upper and lower extremities and hemarthrosis of the knee joint while taking 20 mg of rivaroxaban in a 72-year-old patient with AF without impaired renal and hepatic function. Due to the increase in the residual plasma concentration of rivaroxaban, a pharmacogenetic study and the Thrombodynamics (TD) test were performed. A pharmacogenetic study did not reveal significant gene polymorphisms associated with the metabolism of rivaroxaban. However, TD allowed us to confirm the presence of significant hypocoagulation at the peak of the residual blood concentration of the drug in the blood, which could cause recurrent hemorrhagic events in the patient. In addition, the patient is taking amiodarone at a dosage of 200 mg per day, which does not allow us to rule out drug-drug interaction, despite the inconsistency of the literature data.

The review is devoted to a modern problem of polypharmacy. A universal definition and clear criteria for this concept have not yet been formed, but it is believed that this is the prescribing of at least 5 medications (M). The article discusses the frequency and main causes of polypharmacy, demonstrates its clear relationship with the age. The presence of overweight and obesity, multimorbidity, low physical activity, fragility are clearly associated with polypharmacy. Cognitive impairment, disability, long-term pain syndrome and malignant diseases also predispose to polypharmacy. The absence of a permanent attending physician, living in a nursing home, consulting with several specialists, poor management of medical records are associated with polypharmacy. It is believed that polypharmacy leads to a following number of adverse consequences: it increases the risk of falls, side effects of M, hospitalizations and even death. The main reason for this is the occurrence of various adverse interactions between M, including unpredictable ones, but the causal relationship of these phenomena with polypharmacy is not always proven. To study of adherence to prescribed therapy with polypharmacy is not an easy task, to date, there is no clear answer to the question whether polypharmacy affects adherence to drug therapy. The article presents in detail the problems of potentially irrational prescriptions, discusses the main methods of preventing and combating polypharmacy. Obviously, the most acceptable methods are the cancellation of drugs that are not indicated or contraindicated to the patient, and the prescribing of those drugs for which there are direct indications, but which the patient does not receive. The patient’s therapy should be individualized as much as possible, taking into account numerous factors related to the peculiarities of the disease course, the prognosis, the patient’s lifestyle, his physical and mental status.

The article analyzes the case of the development of ventricular tachycardia and type 2 myocardial infarction (MI) in an 80-year-old patient with a history of coronary artery disease, MI and chronic heart failure. In 2020, the patient was diagnosed with ventricular extrasystole and started antiarrhythmic therapy with diethylamino propionylethoxycarbonylaminophenothiazine 150 mg per day and sotalol 160 mg per day. In 2022, the patient had an episode of clinical death due to ventricular tachycardia with successful resuscitation. A diagnosis of non-ST-elevation acute coronary syndrome was made, coronary angiography was performed, which did not reveal significant coronary stenosis. Upon further examination, the dynamics of biomarkers of myocardial necrosis confirmed the diagnosis of acute MI. In the analyzed case, the development of ventricular tachycardia and MI is most likely associated with the intake of diethylaminopropionylethoxycarbonylaminophenothiazine in combination with sotalol, prescribed in the presence of contraindications to their use.

Heart failure and arrhythmias are pathogenetically closely interconnected and they are mutually aggravating each other. At the same time, tachycardia-induced cardiomyopathy is particularly a reversible disease with proper treatment. This article presents a case report of an elderly patient with hypertension and atrial fibrillation, which are associated to an advanced heart failure and complicating the management of a decreasing kidneys filtration capacity, hematuria and brain stroke. In this case report, tachycardia-induced cardiomyopathy is caused by persistent atrial fibrillation. A complex approach to diagnosis and evidence-based treatment (in particular cardioversion and radiofrequency ablation) made it possible to restore sinus rhythm and compensate heart failure. Dynamics of the clinical state of the patient, laboratory indicators, echocardiographic characteristics allowed us to retrospectively verify atrial fibrillation-mediated cardiomyopathy as the main cause of heart failure progression, and classify this clinical case as heart failure with improved ejection fraction.

Atrial fibrillation is one of the most common cardiac arrhythmias. By all estimates, the number of patients with this arrhythmia will only increase. Currently, the main and most used methods for the treatment of atrial fibrillation are radiofrequency and cryo-balloon ablation. However, the accumulated experience of their use has revealed a number of shortcomings — the lack of long-term pulmonary vein isolation, as well as life-threatening procedure complications. Relatively recent foreign studies showed data on the use of an alternative method of influencing arrhythmogenic foci. The method is based on the use of non-thermal pulsed field ablation, which leads to the appearance of pores in cardiomyocytes and their necrosis, which causes a more stable electrical left atrial pulmonary vein isolation. The margins of the lesions in this exposure are usually very sharp with a narrow transition from normal tissue to tissue with the complete necrosis, while not damaging neighboring structures such as blood vessels, nerves and esophagus. At present, information published in the literature on the use of pulsed field ablation in various fields of medicine, including oncology and cardiology, is clearly not enough. The implementation of this method for the interventional treatment of cardiac arrhythmias is considered a promising direction and is the subject of research by many leading scientific groups around the world. The purpose of this review is to structure the most significant information on the use of pulsed field ablation, presented in the literature, to analyze its possibilities, effectiveness, and disadvantages.

Aim. To study the role of biomarkers in assessing the vulnerability of atherosclerotic plaques.

Material and methods. A review of literature sources investigating the biomarker assessment of the vulnerability of atherosclerotic plaques published for the period 01.01.2016 to 31.12.2022 was carried out. Literature search was carried out in English and Russian in PubMed databases, in Google Academy, Elibrary.ru according to the following keywords: “biomarkers of plaque vulnerability”, “NLR and vulnerable plaque”, “CRP and vulnerable plaque”, ”MMP-9 and vulnerable plaque”, “TIMP-1 and vulnerable plaque”, ”galectin-3 and vulnerable plaque”, “NGAL and vulnerable plaque”. A total of 183 articles were found, of which 42 articles in full-text format containing original clinical studies were selected for the preparation of this review.

Results. Numerous studies have shown that the vulnerability and rupture of the plaque, rather than its size and severity of stenosis, are the main cause of cardiovascular events in patients with coronary heart disease. Small plaques rich in lipids often become unstable due to an inflammatory reaction supported by the interaction between lipoproteins, monocytes, macrophages, T-lymphocytes and vascular wall cells. NLR, CRP, NGAL, Galectin-3, as well as markers of extracellular matrix degradation (MMP-9, TIMP-1) can play a special role in assessing the vulnerability of plaques.

Conclusion. The development of acute coronary syndrome is based on the destabilization of the atherosclerotic plaque, which occurs not only due to changes in its lipid composition, but also infiltration by immuno-inflammatory cells, degradation of the extracellular matrix, as well as an active inflammatory reaction and neovascularization of the plaque. Therefore, traditional imaging methods that characterize the plaque by its appearance and size are not enough to predict the risk of rupture and the development of an acute thrombotic event. Thus, there is a need to identify new biomarkers that would correlate with the instability of plaque atheroma.

The article is devoted to the discussion of modern approaches to the use of laboratory methods to improve the tactics of using direct oral anticoagulants (DOACs) therapy. Clinical situations in which it may be reasonable to use data on the blood concentration of DOACs are given, including very old age, a marked deviation from the norm of body weight or impaired renal function. Data on the role of measuring the blood level of DOACs are considered in cases of the development of diseases or complications in which information is required on the preservation of the anticoagulant effect of DOACs, for example, in the development of severe bleeding or the need for urgent surgical intervention. The advantages and limitations of modern laboratory methods for assessing the blood concentration of DOACs are discussed. It is emphasized that one of the main advantages of using DOACs is the absence of the need to monitor laboratory parameters in most patients. Data from pharmacological studies are presented that may be useful in explaining the mechanisms that determine the higher safety of some DOACs compared to others. Promising methods for assessing the blood level of DOACs, as well as the possibility of using less specific reagents for assessing the concentration of DOACs, are considered. The possibility of using less specific, but more accessible methods for assessing the blood concentration of factor Xa inhibitors, in particular, a reagent for assessing the level of the antifactor, which is used to determine the blood level of heparin, is being considered. The opinions of experts on the role of assessing the blood level of DOACs and the possibility of tactics for selecting doses of DOACs based on laboratory analysis data are given.

Cardiovascular disease is the most common cause of death worldwide. In this regard, there is a need to find and implement effective methods for the prevention and treatment of such diseases. Lifestyle modification is an important component of a complex of preventive and therapeutic measures, including nutrition optimization, increased physical activity, and breaking bad habits. Currently, an actively developing area is the use of biologically active additives to food, in order to replenish the missing nutrients in the diet and maintain health. In the course of the present review, an analysis was made of randomized clinical trials performed over the past 5 years. The studies investigated both the short-term effects of taking omega-3 polyunsaturated fatty acids (effect on the blood lipid spectrum, blood pressure levels) and longterm results (development of myocardial infarction, stroke, cardiovascular mortality). This supplement has demonstrated a positive effect on immediate outcomes, namely the reduction of total cholesterol, low-density lipoprotein, triglycerides (lipid-lowering effect). However, there was no significant effect on long-term results. It also provides information on studies that have examined the cardioprotective effects of supplements such as resveratrol, red yeast rice, L-arginine, and curcumin. An analysis of publications has shown that these supplements have the potential to reduce the risk of development and progression of cardiovascular diseases due to possible hypolipidemic, endothelial protective, and antihypertensive effects. Nutraceutical support can be an effective addition to the basic treatment and help reduce morbidity and mortality due to cardiovascular disease.