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Introduction. Therapy of patients with acute ST-elevation myocardial infarction and massive coronary thrombosis (TTG 3) is a far from solved problem of modern medicine, since often in such patients immediate stent implantation is associated with the development of myocardial hypoperfusion, reducing the long-term prognosis of life.Aim. To evaluate short-term and long-term efficacy and safety of delayed and immediate coronary artery stenting techniques in patients with acute ST-elevation myocardial infarction and massive coronary thrombosis.Material and methods. Comparative study in parallel groups, a total of 153 patients with ST-elevation myocardial infarction and massive coronary thrombosis (TTG 3), 75 patients in the delayed coronary artery stenting group, 78 patients in the immediate coronary artery stenting group. In the immediate coronary artery stenting group, percutaneous coronary intervention was performed in one stage with stent implantation, in the delayed coronary artery stenting group; percutaneous coronary intervention was performed in two stages: the first was achieving TIMI-3 blood flow using a minimally invasive mechanical strategy, the second was control coronary angiography 5-6 days and the decision on the implantation of the stent. The primary endpoint is: the rate of achieving optimal myocardial perfusion according to angiography, the secondary combined endpoint is the rate of major adverse cardiovascular events.Results. In the hospital period, optimal reperfusion (TIMI-3 and MBG 2-3) after the primary procedure was achieved in 88% in the delayed coronary artery stenting group and 69.2% of immediate coronary artery stenting with an advantage in the delayed coronary artery stenting group (p=0.005). Of the 75 patients in the delayed coronary artery stenting group, 38 patients (51%) did not receive a stent in the delayed period due to the insignificance of stenosis on the control coronary angiography. There was no significant difference in the incidence of major adverse cardiovascular events between the groups. In the long-term period, the median follow-up period was 47 months. The frequency of major adverse cardiovascular events was 13.3% in the delayed coronary artery stenting group and 23.1% in the immediate coronary artery stenting group, with a trend towards the advantage in the delayed coronary artery stenting group (p=0.1). Overall mortality (9.3% vs. 11.7%), recurrent myocardial infarction (2.6% vs. 5.1%), target vessel revascularization rate (1.3% vs. 6.4%) were without significant benefit. between subgroups.Conclusion. In patients with ST-elevation myocardial infarction and massive coronary thrombosis, the use of delayed coronary artery stenting gives an advantage in achieving myocardial perfusion after the procedure, and demonstrates a tendency to reduce adverse cardiovascular events in the long-term period.

Aim. TIntroduction. To evaluate in-hospital angiographic and five-year posthospital clinical outcomes of percutaneous intervention strategy without stent implantation with immediate coronary artery stenting technique in STEMI patients with massive coronary thrombosis.Material and methods. The study enrolled 116 patients with primary STEMI myocardial infarction with the signs of massive thrombosis in the lumen of the main epicardial coronary artery with TIMI thrombus grade greater than 3 after antegrade blood flow restoration. In the 1st group of delayed intervention at the primary stage the blood flow was restored by small diameter balloon inflation and/ or manual vacuum thrombus aspiration until stable TIMI grade 3 blood flow was achieved, at control CAG on day 5-6 in 36 people the stent was not implanted due to insignificance of infarct-related coronary artery stenosis (stenosis less than 50% according to QCA). Immediate stent implantation was performed in 78 patients (group 2). The primary endpoint was the incidence of adverse cardiovascular events, including total mortality, recurrent myocardial infarction, repeated revascularization of the infarct-responsive artery. Secondary endpoint: frequency of achieving optimal myocardial perfusion as measured by angiography – TIMI blood flow and Myocardial Blush Grade.Results. The median follow-up period was 47 months. The incidence of the primary end point (MACE) was 15,8% in group 1 and 23,1% in group 2, with no statistically significant difference (p=0,408). Overall mortality (10,5% and 11,7%), the rate of repeat myocardial infarction (2,6% and 5,1%), and the rate of repeat target vessel revascularization (2,6% and 6,4%) were without significant advantage between subgroups. Optimal reperfusion (TIMI-3 and Myocardial Blush Grade 2-3 after primary procedure was achieved in significantly (p=0,02) more patients in group 1 (89%) than in group 2 (69,2%) ST segment resolution ≥70% after intervention was achieved in 87% of cases in group 1 and in 64,1% of cases in group 2 (p=0,011).Conclusion. In STEMI patients with massive coronary thrombosis, the method of delayed percutaneous intervention increases the rate of achieving optimal blood flow and allows avoiding stent implantation in the infarct-related artery in 50% of cases as compared to the method of immediate stenting. Both methods have comparable hospital and five-year clinical risks.

Heart failure (HF) is a global health problem. Despite advances in the development of effective treatments for patients with heart failure, morbidity and mortality from remain high, and the prognosis is poor. However, there is potential to improve outcomes in HF patients with current disease-modifying therapy. Planning needs and resources, assessing the effectiveness of care for HF patients in clinical practice requires high-quality epidemiological data. Previously performed Russian observational studies of HF were characterized by relatively small sample sizes, inclusion of patients in only one or a few regions, strict selection criteria, single-stage design, or short follow-up. The rationale and design of the all-Russian prospective observational multicenter registry study "PRIORITET-CHF", which included 20000 patients with HF throughout the Russian Federation, is presented. The main aims of the study are to (1) describe baseline clinical and demographic characteristics in outpatients with HF in the Russian Federation and (2) characterize routine therapy and evaluate the compliance of treatment for HF with reduced ejection fraction with current clinical guidelines.

Aim. Based on the results of a sociological survey of patients, to assess quality and availability of health care for cardiovascular diseases (CVDs) in 2020-2021 in the Russian Federation.Material and methods. In August-September 2021, 5159 patients with CVDs from 76 Russian regions were interviewed. Questionnaire (Google form) assessed the change in health care provision over the past two years, the availability of medicine provision, the prevalence and reasons for discontinuation of treatment, as well as the difficulties faced by patients.Results. Improvement in health care provision were assessed by 47,6% of the surveyed patients with CVD, worsening — by 16,6%, and 23,7% did not noted any changes. Improvements regarded diagnosis promptness (29%) and timeliness of treatment (28,5%), availability of subsidized medicines (25%) and better patient routing (21%). However, 37% of respondents did not see any improvements in health care system, or found it difficult to answer. The acute problem of access to diagnostics was considered by 24%, inaccessibility of subsidized medicines — by 17%. In addition, 24% of respondents had difficulties in obtaining specialized cardiology care in the polyclinic and 18% had difficulty in obtaining high-quality medical rehabilitation for CVD.Conclusion. In order to increase public satisfaction with the quality of care, public awareness on health maintenance and patients’ rights to receive care should be improved. In addition, possible barriers to obtaining health care should be eliminated, while consultative and diagnostic assistance and subsidized drug provision should be facilitated for receiving.

The objective of this advisory board meeting was to discuss the place of vericiguat in the treatment algorithm for heart failure with reduced ejection fraction and the necessary requirements for its successful application in clinical practice.

Aim: To perform clinical characterization of patients with chronic heart failure (CHF) in the Moscow Region and to assess if their current treatments meet the current clinical guidelines.Materials and methods: Based on the information submitted from 11 outpatient clinics in the Moscow Region in December 2019, we analyzed retrospective data on 286 patients with CHF, including their concomitant diseases, types of assessments and their results, as well as current treatments.Results: The most common concomitant disease was arterial hypertension (95.1% of the patients). 53.8% of the patients had previous myocardial infarction, 37.8%, diabetes mellitus, and 34.6%, atrial fibrillation. Chronic kidney disease was present in 18.5% of the patients, valvular heart disease in 11.9%, and past stroke in 10.5%. Of non-cardiovascular diseases, the most common were gastrointestinal disorders (25.2%), chronic obstructive pulmonary disease or asthma (9.8%), and anemia (5.2%). Only 8% of the patients had one concomitant disease, whereas 72% had 2 to 3 diseases, and 20% had at least 4 concomitant diseases. Mean number of comorbidities per patient was 2.7. Echocardiography had been performed in 82.9% of the cases. Mean left ventricular ejection fraction was 51.0±10.11%; in 11.5% of the patients it was≤40%. Glomerular filtration rate (GFR) was calculated in 58.7% of the patients. 35.9% of the patients had a GFR of less than 60 mL/min/1.73 m2 , in 3.6% it was≤30 mL/min/1.73 m2 . 83.2% of the patients were treated with renin angiotensin aldosterone system blockers (angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, sacubitril/valsartan), 79.0% with beta-blockers, 53.1% with mineralocorticoid receptor antagonists. Glycosides had been administered to 6.9% of the patients, and diuretics, to 51.1%. In most cases, the doses administered were below those recommended by the international clinical guidelines.Conclusion: We have confirmed the need to increase the adherence of doctors to the clinical guidelines on assessment and management of CHF patients.

An online expert meeting held on November 17, 2021 reviewed the results of the randomized, double-blind, multinational, parallel-group EMPULSE trial, evaluating the clinical benefit and safety of the sodium-glucose co-transporter-2 inhibitor (SGLT2i) empagliflozin compared with placebo in patients hospitalized with acute decompensated heart failure (ADHF). Patients were included in the study regardless of ejection fraction (EF) and the presence of diabetes and randomized during hospitalization after stabilization. In addition, the EMPULSE trial used a composite result analyzed using a stratified benefit ratio — Win Ratio analysis. There is evidence of clinical benefit of empagliflozin in hospitalized patients with preserved and reduced LVEF, as well as in patients with newly diagnosed ADHF or with acute decompensation of chronic heart failure (CHF) compared with placebo, regardless of type 2 diabetes presence. The importance of the favorable results of the EMPULSE trial and its significance for clinical practice, which implies the early administration of empagliflozin for inpatients, is noted. A number of proposals have been adopted to accelerate the introduction of empagliflozin into clinical practice for patients with ADHF.

Abstract Introduction Overweight and obesity are increasing worldwide and are associated with an increased risk for cardiovascular disease (CVD). The aim of this study was to examine the burden of CVD risk factors among normal weight, overweight, and obese subjects with hypertension, and to evaluate the effectiveness of switching to a single-pill combination (SPC) of perindopril arginine/indapamide for blood pressure (BP) control in overweight and obese subjects treated in routine clinical practice. Methods FORSAGE was a 3-month, multicenter, observational, open-label study conducted in Russian patients with uncontrolled arterial hypertension under previous antihypertensive therapy. Subjects were switched to the full-dose perindopril arginine 10 mg/indapamide 2.5 mg SPC. BP was assessed at 2 weeks, 1 month, and 3 months, and serum creatinine and general health status at 3 months. The present post hoc analysis of the FORSAGE study results explored the effectiveness of perindopril arginine/indapamide SPC in patients with arterial hypertension with regard to baseline body mass index (BMI): normal (

The conclusion of the Expert Council reports an agreement on the place of the P2Y12 receptor blocker prasugrel in the early invasive treatment of patients with acute coronary syndrome ACS, according to the results of the multicenter randomized controlled study ISAR-REACT 5. Prasugrel should be considered the preferred P2Y12 receptor blocker in the planned primary percutaneous coronary intervention and early invasive management of patients with ST segment elevation ACS. Herewith, prasugrel intake in patients with non-ST segment elevation ACS is preferable after coronary angiography and decision for coronary stenting.

The lecture is devoted to the choice of tactics and the rules of reperfusion therapy for ST-elevated myocardial infarction. Since the time of reperfusion is crucial for the survival of these patients and the preservation of a viable myocardium, proper organization of care and strict adherence to the guidelines for drug-induced and non-drug interventions is necessary. The lecture substantiates the tactics of pharmaco-invasive intervention, the choice of thrombolytic agent, provides data on indications and contraindications for thrombolytic therapy, dosing regimen of thrombolytic drugs, other antiplatelet and anticoagulant drugs required for reperfusion. Knowledge of current guidelines should help reduce ischemia time and cases of unjustified refusal to effective interventions.

The expert consensus of the Russian communities discusses the issues of comprehensive medical rehabilitation of patients with coronavirus disease 2019 (COVID-19). COVID-19 is a contagious infectious disease that can cause pulmonary, cardiac, motor, metabolic, neurocognitive and mental disorders, that is, multiple organ dysfunction. COVID-19 survivors, especially after a severe clinical course, face serious psychological and physical problems, posttraumatic stress, cognitive dysfunction, nutritional deficiencies and exacerbation of concomitant chronic diseases. Some patients, regardless of the COVID-19 severity, have a long clinical course of the disease (“chronic-COVID”, “long COVID”). There is evidence of post-acute COVID-19 syndrome. In this regard, patients after COVID-19 will need rehabilitation measures. The expert consensus of the Russian communities presents general principles, stages and aspects of medical rehabilitation after COVID-19, indications and contraindications for rehabilitation interventions. The paper includes recommendations on comprehensive cardiac and pulmonary rehabilitation, as well as specifics of rehabilitation care for different COVID-19 courses within the national three-stage rehabilitation system.

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

At the online meeting held on September 3, 2020, the results of the international multicenter trial EMPEROR-REDUCED were considered. Number of proposals and recommendations for the further study of cardiovascular and renal effects of empagliflozin and its practical use in heart failure patients were agreed.

Relationships and Activities. The Council of Experts was supported by AstraZeneca.

Arterial hypertension in adults. Clinical guidelines 2020

L-carnitine (LC) and its esters do not only participate in the metabolic exchange of the cardiac myocytes (they are responsible for transfer of long-chain fatty acids from the cytoplasm in mytochondria) but have other vital types of activity. They have antioxidant and anti- nflammatory effect at various levels. LC is proved to be a direct antioxidant and to remove already formed oxygen radicals as well as to suppress generation of oxygen radicals by cytoplasmic and membrane-connected ferments as a result of formation of complexes with iron and copper ions in their active centers. The leading reason of LC protective effects is change of activity of redox-sensitive signal paths targeted at nuclear receptors (they are factors of NF-kB; PPARs; Nrf2, AP1 etc. gene transcription). These factors control activity of a group of genes responsible for survival and stability of the cardiovascular system to various types of stress, including oxidative stress, and prevent loss of cardiac myocytes and endothelial cells at ischemia/reperfusion and other hypoxia-conditioned pathologic states. The review considers a number of mechanisms participating in protective effects of LC and its derivatives in the heart and other oxygen-dependent organs and tissues.

Aim. To study the influence of metabolic cytoprotector trimetazidine on the heart rate variability (HRV) in patients with stable ischemic heart disease (CHD).Material and methods. Into the simple, prospective, non-randomized trial totally 50 patients included with stable CHD, continuously showed positive stress test on treadmill. HRV was investigated on the short episodes of recording (the device and software of MEDASS, Russia) before and after 4-month therapy by trimetazidine 35 mg BID in supine position and during the 10-minute active ortostatic test. The temporal and frequency parameters of HRV were assessed.Results. HRV in CHD patients is decreased and the prominence of the decrease depends upon gender, age, diabetes mellitus and ejection fraction. After the shift from supine to upright position with normal reaction of heartrate there was decrease of RR-interval moda and normalized value in the area of high-frequency component, the vegetative balance index increased, as the centralization index, that shows on the decrease of parasympathetic influence. While being treated by trimetazidine the HRV parameters were increased in the temporal area – variational amplitude between maximal and minimal values, also there was decrease (improvement) of vegetative balance index and index of regulatory systems tension.Conclusion. Trimetazidine in patients with stable CHD increases the decreased at baseline HRV and normalizes the reaction on ortostatic test. Its effects can be explained by the decrease of ischemia, oxidative stress and improvement of nitric oxide bioavailability.

Aim. To study the influence of biogenic stimulators Actovegine and Zifodine (deproteinized hemodrivates of calf blood) on reactive oxygen species formation by blood phagocytes in patients with chronic heart failure (CHF).Material and methods. Reactive oxygen species formation was registered by lucigenine-dependent chemiluminiscence on the luminomenter “Biotox-7” (Russia) in 20 patients with CHF of II-III functional classes by NYHA. The hemiluminiscences basal and stimulated by farbolic ether (RMA) were measured, as also inhibitory activity of Actovegine and Zifodine.Results. In CHF patients’ blood there was “spontaneous” secretion superoxide anion radicals, that is showing presence of preactivated phagocytes. In addition, a significant increase of oxygen radicals is shown as a response to RMA (1 mcM). Actovegine and Zifodine dose-dependently suppressed prominence of the response. While concomitantly applied Actovegine and Zifodine at the RMA background there was additive inhibitory effect found, which was not depended on consequence of additives.Conclusion. Actovegine and Zifodine decrease reactive oxygen species secretion by phagocytes, which are extracted from the blood of CHF patients. Addictiveness of such inhibitory effects of Actovegine and Zifodine shows absence of their identity by structure and of improper translation of this data into conclusions on effectiveness and safety, found in clinical practice while prescribing Actovegine and Zifodine.

Aim. To assess the effects of the four-month trimetazidine MR therapy on the parameters of 24-hour electrocardiogram (ECG) monitoring and heart rate variability (HRV) in patients with stable coronary heart disease (CHD).Material and methods. This prospective, non-randomised study, with the inclusion of 66 consecutive patients who had stable CHD and stable stress test results, investigated the effects of trimetazidine MR therapy on the parameters of 24-hour ECG monitoring and HRV.Results. Trimetazidine MR did not markedly affect the 24-hour, daytime, or nighttime levels of heart rate. Trimetazidine MR therapy was not associated with any substantial changes in frequency and time-domain HRV parameters or in the incidence of cardiac arrhythmias. However, there was a significant reduction in the number of patients with ST segment depression (from 66,7% to 43,8%; p

The study aim was to assess the importance of adequate administration of medications with negative chronotropic effect in the improvement of clinical course and prognosis among patients with coronary heart disease (CHD) and heart failure. The possibility and appropriateness of combination therapy with β-adrenoblockers (β-AB) and an If channel blocker ivabradine is justified. The authors analyse current real-world trends in the administration and dose titration of these medications among ambulatory Russian patients. Russian doctors need to be more active in the treatment of patients with CHD and heart failure and better understand the need for and benefits of dose titration of medications with negative chronotropic effect, as well as the importance of combination therapy for the improvement of clinical course, prognosis, and quality of life.

This review presents the modern views on the effectiveness of water-soluble angiotensin-converting enzyme (ACE) antagonists and calcium antagonists (CA), as monotherapy or as fixed-dose combination therapy, in the treatment of arterial hypertension (AH). The results of the X-ray structural analysis of crystal ACE-lisinopril complexes suggest a highly selective, strong inhibitory effect of lisinopril on various ACE forms of the hormonal renin-angiotensin-aldosterone system and tissue renin-angiotensin systems. The association between specific action mechanisms and therapeutic effects in hypertension is analysed for a third-generation CA amlodipine. The benefits of a fixed-dose combination medication Ekvator (amlodipine 5 mg plus lisinopril 10 mg) in hypertension are described, including its synergetic protective effects.

Aim. To assess the effectiveness and safety of the full-dose combination therapy with perindopril (10 mg) and indapamide (2,5 mg) in patients with arterial hypertension (AH). Material and methods. The simple, non-randomised, prospective study included 36 patients with Stage 1-2 AH. Treatment effectiveness was assessed by the reduction in office blood pressure (BP) levels, results of the 24-hour BP monitoring (BPM), morning BP surge (MS), BP load area and time, BP variability, and diurnal index. Safety parameters included the levels of sodium, potassium, glucose, hepatic aminotransferases, urea, creatinine, and the presence of hypotension episodes. Statistical analysis was performed in SPSS 12. Results. The three-month therapy resulted in the achievement of target levels of systolic and diastolic BP (SBP, DBP) in 83% and 100% of the patients, respectively. According to the 24-hour BPM results, there was a significant reduction in the levels of SBP24 (from 148,3±18,2 to 134±11,1 mm Hg; p=0,001), DBP (from 84,8±12,3 to 76,9±9,1 mm Hg; p=0,001), and pulse BP (from 64,0±14,6 to 58,4±9,6 mm Hg; p=0,012). There was also a significant reduction in the load time indices of SBPday (from 72,5% (95% confidence interval, CI, 43,3-95,3) to 46,5% (95% CI 16,3-64,0); p=0,001) and DBPday (from 84,5% (54,0-100,0) to 57,0% (35,0-82,3); p=0,002). MS velocity decreased for both SBP (from 16,4 (12,5-25,1) to 12,7 (10,8-15,8) mm Hg (p=0,017) and DBP (from 15,8 (10,2-22,0) to 12,2 (9,3-17,8) mm Hg (p=0,019). During the therapy course, no hypotension episodes or marked changes in blood biochemistry and electrolyte parameters were registered. Conclusion. Initiating antihypertensive therapy with a full-dose combination of perindopril and indapamide was both effective and safe.

Aim. To study the effects of a thiazide-like diuretic indapamide (Ind) on the levels of free oxygen radicals generated by blood phagocytes and isolated neutrophils in patients with heart failure (HF). Material and methods. Using whole blood samples and isolated neutrophils of 16 HF patients (NYHA Functional Class II–III), the generation of free oxygen radicals was examined with a chemiluminometre “Biotox-7”, in the presence of luminophores – lucigenin (30 mkM) and luminol (50 mkM). The standard stimulators of blood phagocytes and neutrophils were bacterial tripeptide (FMLP, 3 mkM) and phorbol ester (PMA, 1 mkM). The generation of superoxide anions (O2-) and hydroxyl radicals was continuously assessed by the number of impulses per second and presented as integral chemiluminescence (summary value for 10 minutes). Inhibiting effects of varied Ind concentrations were assessed by the decrease (%) in the peak stimulated luminescence. Antioxidant activity of Ind was studied in the cell-free medium generating hydroxyl radicals. Statistical analysis of the data was performed with the use of SigmaPlot software. Results. At baseline, the blood of HF patients contained pre-activated (primed) phagocytes, as shown by the “spontaneous” production of superoxide anions due to neutrophil adhesion on cuvette walls. PMA markedly increased the production of oxygen radicals. In the neutrophil suspension, Ind dose-dependently (0,5–2 mkM) reduced the peak PMA response levels of superoxide anions up to the baseline levels. Moreover, Ind demonstrated a similar effect in whole blood samples of HF patients. FMLP increased the production of oxygen radicals and potentiated the subsequent response of phagocytes to PMA. Ind (2 mkM), when added after FMLP and PMA, reduced the post-stimulation levels of superoxide anions up to baseline values. The initial exposure of blood samples to Ind decreased spontaneous generation of oxygen radicals and the magnitude of subsequent response to FMLP and PMA. Antioxidant effects of Ind were also observed in the cell-free medium, which suggests a direct interaction between Ind and oxygen radicals. Conclusion. Low Ind concentrations provided a marked antioxidant effect, which could be clinically significant in the management of HF patients.

Electrocardiography is the most accessible and widely used method for diagnosing myocardial infarction (MI) and predicting MI outcomes. This paper presents the results of the prospective study, assessing ST segment dynamics in 248 MI patients and evaluating its role in predicting short-term (3 months) post-hospital MI outcomes. At least once (at admission, at Days 6-8, or at discharge), ST segment elevation was registered in 117 MI patients (47%), and ST segment depression – in 134 (54%). Among these participants, persistent ST elevation/depression, registered at all control points, was observed only in 15%: two thirds (26 out of 37) had persistent ST elevation, and the others – persistent ST depression. During the three-month follow-up period, a combined endpoint (cardiovascular death, non-fatal MI, stroke, or unstable angina) was registered in 48 participants (19,7%; the endpoint was evaluated in 245 patients with known post-hospital outcomes). Independent predictors of poor post-hospital MI prognosis included persistent ST elevation (odds ratio 2,9; 95% confidence interval 1,2-7,0) and persistent ST depression (odds ratio 4,3; 1,2-14,8), but not episodic, non-persistent ST elevation/depression.

The study investigated the medical assessment of arterial hypertension (AH) severity and its association with seeking urgent medical assistance (ambulance calls and hospitalizations). The main criteria for medical assessment of AH severity were the patients’ self-evaluation of their status, systolic blood pressure level, and self-assessment of the pre-administered AH therapy effectiveness. The prognostic value of medical assessment of AH severity was relatively low, with sensitivity of 51% and specificity of 74% for visual analogue scale (VAS) assessment (≥55 points). The more accurate instrument for assessing the risk of seeking urgent medical assistance was the SCORE risk scale (risk level ≥2,4%). Patients’ self-assessment of their status with VAS had additional prognostic value. All three methods combined could result in sensitivity of 90%, but specificity of 34%. The doctors linked their assessment of AH severity with a necessity to use more antihypertensive medications in more severe patients. However, among patients with medically assessed severity ≥55 VAS points, adding indapamide retard to the therapy resulted in a significant reduction in the risk of seeking urgent medical assistance (odds ratio 0,36; 95% confidence interval 0,20-0,73). No such effect was observed in medically assessed “non-severe” patients.

Aim. In patients with acute coronary syndrome (ACS), to detect pre-activated (primed) phagocytes in peripheral blood and to evaluate the effects of trimetazidine MB, when added to standard therapy, on reactive oxygen species (ROS) production. Material and methods. In 113 hospitalised ACS patients – 86 with myocardial infraction (MI) and 27 with unstable angina (UA) – the dynamics of blood leukocytes and ROS (baseline activity and PMA (phorbol-12-myristate-13-acetate) stimulated activity) was assessed by lucigen-dependent chemiluminescence method. In 60 participants, trimetazidine MB (70 mg/d) effects on ROS production were investigated. Results. At hospital admission, blood leukocyte levels, basal and PMA-stimulated ROS production were significantly higher in AMI patients (especially in those who subsequently died) than in UA participants. Trimetazidine MB therapy facilitated more rapid and manifested leukocyte count reduction, compared to the standard therapy alone: the respective reductions at Days 3-5, 7-10, and 15-21 were -20 vs. -14%, -37 vs. -30%, and -47 vs. -32%. In the trimetazidine MB group, the basal and PMA-stimulated ROS production did not change significantly, while in the standard therapy group, the ROS production increased from Day 3 to Day 15.Conclusion. Adding trimetazidine MB to standard therapy of ACS patients significantly reduced the peripheral blood leukocyte count at Days 15-21, without leukocyte activation in the sub-acute phase of myocardial ischemia.

Aim. То analyse trimetazidine therapy potential in unstable angina (UA).Material and methods. In a randomised, placebo-controlled study including 50 UA patients, the effects of adding trimetazidine MB to standard therapy on angina attack dynamics, total ST depression and QT duration were evaluated. Clinical outcomes were registered during 6 months of the follow-up.Results. In trimetazidine patients (main group, MG), angina attack number reduced after 7 days of the treatment, as well as 30 days and 6 months later — 2,70±1,06, 0,50±0,09 and 0,7±0,12 per week, respectively, comparing to the control group (CG) receiving standard therapy only — 7,10±0,95 (p

Aim. To investigate how trimetazidine (TMZ) directly affects oxidative phosphorylation in intact mitochondria (MCH), isolated from the animals not undergoing ischemia-reperfusion process.Material and methods. Rat liver MCH were isolated by standard methods. Oxidative and phosphorylating MCH functions were studied by polarigraphic methods. TMZ was used in the concentrations of 10-4 М and 10-5 М.Results. TMZ in concentrations of 10-4 М and 10-5 М decreased the time of added adenosine diphosphate (ADPH) phosphorylation, reduced the amount of oxygen (O2) necessary for this phosphorylation, and increased ADPH/O2 coefficient. Therefore, phosphorylation velocity and effectiveness increased, i.e. O2 use became more economical, and ATPH synthesis increased. TMZ also increased breath control, which pointed to oxidation and phosphorylation association. TMZ per se did not separate these two processes.Conclusion. MCH energetic function improvement is one of the key factors in TMZ cytoprotective effects.

Aim. To study the role of lipoprotein lipase (LPL) gene HindIII polymorphism in hospital and post-hospital prognosis of acute coronary syndrome (ACS).Material and methods. The study included 423 ACS patients. In 382 participants with verified myocardial infarction (MI) and unstable angina (UA), LPL gene HindIII polymorphism was analyzed. Hospital and post-hospital (one-year) ACS outcomes were registered.Results. The prevalence of LPL gene Н+/+, Н+/- and Н-/- genotypes was similar among patients with MI and ST segment elevation (ST-MI) and participants with MI, UAand no ST segment elevation (non-ST-MI). At the same time, among those under 65 years, genotype patterns were different in ST-MI vs. UA patients (df=2, p=0,017), mostly due to high prevalence of Н+/+genotype (77 % and 42 %, respectively). Genotype distribution in non-ST-MI patients could be described as intermediate. Hospital and post-hospital lethality, as well as non-fatal ACS complication rate, was similar in different genotype groups. Lethality risk, calculated by hospital risk scale, was higher in elderly Н+/+ carriers. Age-related increase in post-hospital lethality was typical only for Н+/+ carriers (for every 5 years, adjusted risk of cardiovascular death increased by 2,89 (1,23; 6,76) times). No similar tendency was observed for Н- carriers.Conclusion. LPL gene Н+/+ genotype was associated with ST-MI, but only in those under 65 years. Elderly carriers of this genotype had relatively high risk of hospital and post-hospital death

Literature data analysis demonstrates that classical beta-adrenoblockers and thiazide diuretics, even in combination with ACE inhibitors, could be associated with incident cases of diabetes mellitus (DM) in patients with arterial hypertension (AH). In people with high risk of DM development, metabolically neutral medications should be used, e.g., ACE inhibitors, sartans, and calcium antagonists, as well as combined medications.

Aim. To investigate the effects of an anti-ischemic medication trimetazidine on Са2+ ion metabolism in human leukocyte and monocyte precursors – HL-60 promyelocytes.Material and methods. HL-60 cells were cultivated in vitro. Changes in intracellular free Са2+ ion concentration were registered with fluorescent Са2+ probes Fura-2. Results. For the first time it was demonstrated for differentiated and non-differentiated HL-60 cells that an antianginal agent trimetazidine suppressed the activity of plasmatic membrane store operated Са2+ channels (SOC channels). Importantly, trimetazidine did not cause Са2+ ion release from the stores and did not open SOC channels, in contrast to other SOC channel inhibitors, e.g., miconazole. In open SOC channels, trimetazidine and miconazole targeted the same binding areas.Conclusion. The results obtained demonstrate additional trimetazidine effects, linked to selective SOC channel blockade. It provides new potential explanations for trimetazidine effects on electro-inert cells (e.g. blood phagocytes) and its effects in myocardial ischemia.

Aim. To study effects of adding isosorbide dinitrate (ID) and trimetazidine MB 35 mg (Tr) to beta-adrenoblocker therapy in stable angina (SA) patients. Material and methods. In total, 40 patients with Functional Class II-III SA were examined. Combined therapy effectiveness was studied in a three-month randomized, open, comparative, parallel trial. Physical stress tolerance (PST) in treadmill test, angina attack incidence, nitrate dose, and health self-assessment dynamics (visual analogue scale) were assessed. Results. In both groups, PST increase by Month 1 was similar: 17% and 19%, respectively. Then PST stayed the same in ID group, and further increased in Tr group. By Month 3, PST in Tr group was twice as high as that in ID group: 15% and 34%, respectively. In Tr group, ST depression reduction, comparing to the baseline, was greater than in ID group: 49% vs 27%, respectively. It was associated with reduced angina attack incidence and need in short-acting nitrates. General health self-assessment improved by 20% (Month 1) and 35% (Month 3), comparing to 13% and 18% in ID group, respectively. Two participants dropped out of ID group, due to low medication tolerability (n=2), and myocardial infarction development (n=1). Conclusion. Comparing to ID, Tr demonstrated better tolerability profile, and long-run tolerance effect absence.

The authors propose prognostic models for separate assessment of post-hospital death risk in males and females, hospitalized with acute coronary syndrome, ACS (possible myocardial infarction or unstable angina). The models are based on parameters registered at admission and further calculation of death risk during one-year post-discharge follow-up period. This predicted risk gives a chance to divide patients into risk groups - with minimal (lethality < 1 %) to maximal (lethality > 30 %) risk, as well as to predict possible time of death. Reproducibility of prognostic results was confirmed for new ACS cases.

The authors propose a prognostic model for assessing death risk in patients hospitalized with acute coronary syndrome (possible myocardial infarction or unstable angina). The model is based on parameters registered at admission and further calculation of death risk during in-hospital follow-up period. This predicted risk gives a chance to divide patients into risk groups - with minimal (lethality 40 %) risk. This highly effective technology provides reproducible prognostic results.

Aim. To study the gender-specific perspectives of in-hospital outcome prognosis in acute coronary syndrome (ACS) patients. Material and methods. In total, 1035 consecutive patients with acute myocardial ischemia were included in the study. The role of clinical and laboratory parameters in ACS prognosis was assessed by binary logistic regression. Results. Under age of 65 years, ACS in males resulted in Q-myocardial infarction (MI) more often (23.4%) than in females (9.7%; p

Aim. The principal objective of this randomized, comparative, open clinical trial PRESTIGE was to determine the time of achieving optimal therapeutic dozes of ACE inhibitors. The secondary goal was to assess dynamics of chronic heart failure (CHF) functional classes (FC) during the treatment. Material and methods. The study involved 125 patients with Q-wave acute myocardial infarction (MI): 68 males, 57 females; mean age 67 years. All participants were randomized into perindopril or captropril groups (n=63 and 62, respectively). In dose titration, starting doses were 2 mg/d and 18.75 mg/d, respectively. Recommended daily doses were 4-8 mg once per day for perindopril, and 75-150 mg, three times per day, for captropril. Treatment and follow-up period lasted for 6 months. ACE inhibitor efficacy was assessed by measuring brain natriuretic peptide (BNUP) levels - at baseline, Weeks 8 and 24. Quality of life (QoL) was assessed by two methods: by “health line” and standard Minnesota University Questionnaire for heart failure patients. Incidence of death and hospitalization due to cardiovascular causes was also registered. Results. At Week 8, there was a significant reduction in BNUP level (to 296.5±16.7 pmmol/l; or by 25.4%; р=0.004) in perindorpil group, and to 342.7±13.8 pmmol/ml (by 19.1%; NS; р=0.06) in captopril group. At 6 months, QoL improved in perindopril group (reduced total QoL score, 23.8; р=0.047), and did not change comparing to Week 3, in captopril group (31.4). Conclusion. MI patients with left ventricular dysfunction, early administered ACE inhibitors, achieved target dose of perindopril faster than that of captopril. That was associated with improved clinical course (CHF FC, QoL) in perindopril group.

Aim. To assess moexipril clinical efficacy, safety, and target organ protection in postmenopausal women. Material and methods. An open, randomized, non-comparative trial involved 32 postmenopausal women (mean age 63.17±0.87 years), with arterial hypertension (AH) mean duration of 10.4±2.3 years, Sixteen-week moexipril therapy influence on blood pressure (BP) level (office measurement and 24-hour BP monitoring), vascular function, and microalbuminuria (MAU) in morning urine portion, was investigated. Results. Target BP level was achieved in 29 out of 30 patients: 9 women received 7.5 mg/d of moexipril, 13–15 mg/d, 8–15 mg/d, plus hydrochlorthiazide (12.5 mg/d); 2 women were excluded due to adverse events. Office BP level declined from 164.33±1.45/94.50±0.89 mm Hg to 133.5±0.57/81.5±0.65 mm Hg. In 24-hour BP monitoring, day- and nighttime BP levels decreased, as well as pulse BP, and BP variability. In reactive hyperemia and nitroglycerine tests, vasodilatation increased by approximately 50% and 40%, respectively. MAU significantly reduced from 28.28±3.94 to 8.10±1.00 mg/l (p

The authors analyze the results of principal studies focused on cardiomyocyte (CMC) energy metabolism in normal physiological state and ischemia. Special emphasis is put on mechanisms of regulation and interaction of main energetic substrate oxidation processes, as well as on chemical substances and pharmaceutical agents affecting key stages of energetic metabolism in ischemia. Medications that partially reduce fatty acid (FA) oxidation in ischemic myocardium, demonstrate cytoprotective action. Their clinical safety is explained by preventing CMC accumulation and toxicity prevention of FT and their products.

Heart pace-maker activity is controlled by highly specialized sinus node (SN) myocytes. This control is linked to functional activity of f-channels providing Na+ and К+ If current. F-channels are activated by plasmatic membrane hyperpolarization in pace-maker cells, at diastolic values of membrane potential. Recent experiments have demonstrated that If current activates slow diastolic depolarization (DD) and regulates the rate of this process, together with endogenous neuromediators and exogenous chemical agents. Decrease in the quantity of open f-channels reduces If current, DD rate and increases threshold membrane potential time. As the result, heart rate (HR) decreases. If current is also controlled by cAMP binding to f-channel proteins. cAMP level in SN myocyte cytoplasma is influenced by autonomous nervous system (ANS) neuromediators. This is the mechanism for ANS regulation of HR in physiological settings. Search for chemical agents selectively targeting f-channels resulted in the development of a new medication, ivabradine (Coraxan®), which is used for angina treatment in patients with sinus rhythm. The medication decreases HR by If current reduction and DD time increase. Importantly, ivabradine does not affect other ion channels.

Aim. То investigate the association between ID polymorphism of ACE gene and acute coronary syndrome (ACS) development and progression. Material and metliods. This prospective study analyzed hospital and post-hospital (one-year) outcomes in 376 patients with myocardial infarction (MI) or unstable angina (UA), as well as outcome association with ACE gene ID polymorphism. Results. Q-wave IM risk in ACE gene DD genotype patients was 2,1 and 2,5 times higher than in participants with ID or II genotypes, respectively. On the contrary, UA episodes in these patients were significantly less frequent, being registered in 24,8%, 45,8%, and 52,3% of the subjects with DD, ID, and II genotypes, respectively (df=2; p

Aim. To compare the effectiveness of the combination therapy with ivabradine and β-adrenoblockers (β-AB) and the dose-titration β-AB therapy. Material and methods. This multi-centre, open, controlled study included 1104 patients with functional Class (FC) II-III stable angina (SA), sinus rhythm, and heart rate (HR) ≥60 bpm, who received regular β-AB therapy in submaximal doses. The participants were divided into the standard therapy group (β-AB therapy with the dose titration to the maximal tolerated dose; 228 patients (20,7%)) and the ivabradine therapy group (876 patients (79,3%))Results. Both groups were comparable by main demographical and clinical characteristics. Adding ivabradine to the β-AB therapy resulted in a more pronounced HR reduction at Week 16, compared to the standard therapy group (61±6 vs. 63±8 bpm; p=0,001). By the end of the study, the percentage of the patients with FC I SA was significantly higher in the ivabradine group than in the standard therapy group (37,1% vs. 28%; p=0,017). The average number of angina attacks between Weeks 8 and 16 was significantly lower in the ivabradine group than in the standard therapy group – 4 (2;10) vs. 6 (2;15), respectively (p=0,015). In the standard therapy group, the incidence of adverse events, such as dyspnoea, hypotension, and fatigue, was significantly higher than in the ivabradine group – 18,4% vs. 9,4%, respectively (p

Aim. To pharmacoeconomically estimate the use of a fixed-dose combination of perindopril and amlodipine in the treatment of hypertensive patients. Materials and methods. A pharmacoeconomic study was conducted on the basis of the Russian postmarketing observational open program POTENTIAL, which included the estimation of direct and indirect costs associated with the addition of a fixed-dose combination of perindopril and amlodipine to conventional therapy for hypertension in patients who had not achieved adequate blood pressure (BP) control. Cost-difference, cost-effectiveness, and budget-impact analyses were carried out. Results. The addition of prestance to conventional therapy for hypertension can reduce total costs by 5.-5.8 times, direct costs required to achieve 1% of patients with adequate BP control by 20.5-42.1 times, and direct costs to improve a patient’s status by one visual analogue scale score by 1.03-2.11 times. Within a 5-year horizon, the administration of prestance can decrease the cost of therapy for high BP and related strokes by 1.39-1.46 times. Conclusion. Due its high efficacy, prestance (amlodipine + perindopril) is a pharmacoeconomically preferred alternative only to the conventional therapy for hypertension even if the least costly generics are used, in both the short and medium term.