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Aim. To study the long-term effects of complex therapy with the addition of enhanced external counterpulsation (EECP) in patients with stable coronary artery disease (CAD) complicated by chronic heart failure (CHF).Material and methods. In the open randomized trial EXCEL (NCT05913778), 118 Patients with the verified ischemic CHF NYHA class II-III with reduced or intermediate left ventricular ejection fraction were included. They were randomized into group 1 (n=59) — optimal medical therapy (OMT) and EECP (35 hours, 2 courses per year), group 2 (n=59) — OMT and EECP (35 hours, 1 course per year). The primary endpoint was the proportion of patients with a 6-minute walk test (6MWT) increase of at least 20% from baseline. The secondary composite endpoint included adverse cardiovascular clinical outcomes (myocardial infarction, revascularization, stroke, death), new cases of atrial fibrillation, diabetes mellitus, decreased renal function, and hospitalizations for CHF.Results. The average CHF NYHA class decreased in group 1 from 2.41±0.49 initially to 1.95±0.47 after 24 months (p20% (primary endpoint) in groups 1 and 2 after 24 months was 98.3% (n=58) and 79.7% (n= 46) respectively (p20%) — 16.4 times lower (odds ratio 0.061, 95% confidence interval 0.008-0.484; p=0.009).Conclusion. Over the 24-month study period, the effect of EECP in patients with coronary artery disease complicated by CHF demonstrated a stable improvement in exercise tolerance, as well as a decrease in the incidence of adverse clinical outcomes, significantly more pronounced in the group with a large number of EECP procedures

Aim. To characterize autoimmune reactions in patients with chronic cardiac failure (CCF) of different etiology. Material and methods. Basic markers of immune activation were measured in 43 patients with coronary heart disease stage I-IIB (NYHA FC I-IV) and 44 patients with dilated cardiomyopathy (DCMP) stage I-IIB (NYHA FC I-IV). Antibodies to myocardial tissue were studied with indirect immunofluorescence. Echocardiography was made by standard recommendations with evaluation of systolic and diastolic left ventricular function. Concentrations of C-reactive protein, IgG, IgA, IgM were estimated nephelometrically. Enzyme immunoassay studied serum levels of IL-8, IL-2R, IL-6, IL-18, IL-10, IFN-gamma, endothelin. Results. Patients with DCMP had higher titers of antimyocardial autoantibodies than in coronary heart disease (CHD) reflecting more severe autoimmune inflammation. In CHD endothelial, systolic and diastolic dysfunctions severity correlated with severity of inflammation. Conclusion. Some characteristics of autoimmune reactions in CCF determine severity of the disease course.

Aim. To study the effect of various therapy regimens with enhanced external counterpulsation (EECP) on exercise tolerance, quality of life, indices of structural and functional state of cardiovascular system in patients with stable coronary artery disease (CAD) complicated by chronic heart failure (CHF).Material and methods. The study included patients with stable CAD complicated by CHF with reduced and intermediate left ventricular ejection fraction (LVEF) from the randomized EXCEL trial (NCT05913778; n=120) and additionally patients with similar inclusion and exclusion criteria (n=90) who were randomized into groups with different EECP treatment regimens for 12 months: Group 1 (n=40): course of 35 hour-long procedures; Group 2 (n=40): course of 35 hourlong procedures every 6 months; Group 3 (n=30): course of 20 hour-long procedures then constantly 1 hour per week; Group 4 (n=30): constantly 2 hours per week; Group 5 (n=30): course of 20 hour-long procedures then constantly 2 hours per week; Group 0 (placebo ; n=40): course of 35 hour-long procedures with compression pressure 80 mm Hg. All patients at baseline and after 12 months were assessed for clinical status, quality of life (MLHFQ, SF-36), NT-proBNP levels, LVEF, as well as exercise tolerance (6-minute walk test; 6MWT) initially, after 3, 6, 9 and 12 months. Correlation analysis and risk assessment of adverse events (combined endpoint — combination of cases of adverse cardiovascular events, deaths, hospitalizations for CHF, new-onset of atrial fibrillation, diabetes, decreased renal function) was performed.Results. Treatment effectiveness had positive correlation with EECP duration (r(S)=0,670; p20% after 12 months was 7,7%, 72,5%, 97,5%, 76,7%, 90%, 100%, respectively. Cumulative event-free survival was highest in groups 5, 4, and 2 (0,97, 0,93, and 0,86, respectively), and the risk of developing combined endpoint in these groups was minimal (0,035, 0,075, and 0,150, respectively).Conclusion. The effect of EECP treatment in patients with coronary artery disease complicated by CHF depended on the EECP hours and regimen. Alternative EECP regimens (with more treatments spread evenly over the year) in addition to optimal medical therapy may improve the management of these patients.

От имени исследователей программы АПРЕЛЬ - Метаболический синдром (МС) в последние годы привлекает к себе повышенное внимание медицинской общественности. Это обусловлено не только широким распространением данного симптомокомплекса в популяции, но и тем, что у пациентов с МС риск развития сердечно-сосудистых осложнений в 2–10 раз выше, чем у лиц без метаболических нарушений. Основную роль в развитии сердечно-сосудистых осложнений у больных с МС играют артериальная гипертония (АГ), дислипидемия и гипергликемия. При этом особое значение в последнее время придается повышенному уровню глюкозы после еды, так называемой постпрандиальной гипергликемии. В целом ряде исследований было показано, что именно постпрандиальная гипергликемия является самостоятельным фактором риска развития ишемической болезни сердца и мозгового инсульта. Одним из наиболее эффективных и безопасных лекарственных средств, способных влиять на постпрандиальную гипергликемию, является акарбоза. Механизм действия препарата заключается в обратимой блокаде a-глюкозидаз (сахараза, глюкоамилаза, мальтаза) в верхнем отделе тонкой кишки. Это приводит к нарушению ферментативного расщепления поли- и олигосахаридов и всасыванию моносахаридов, вследствие чего предотвращается развитие постпрандиальной гипергликемии и снижается уровень инсулина. Результаты научного исследования, проводимого в отделе системных гипертензий НИИ кардиологии им. А.Л.Мясникова у пациентов с АГ, нарушенной толерантностью к глюкозе (НТГ) и ожирением, продемонстрировали способность акарбозы позитивно влиять не только на углеводный обмен, но и на обмен липидов, а также снижать избыточную массу тела и повышенный уровень артериального давления (АД).Результаты научных работ и крупных международных исследований по изучению влияния терапии акарбозой на развитие сердечно-сосудистых заболеваний и СД типа 2 у больных с НТГ послужили основанием для проведения Российской многоцентровой программы АПРЕЛЬ (Многоцентровая рандомизированная программа по изучению эффективности применения Акарбозы у Пациентов с наРушенной толЕрантностью к глюкозе и артериаЛЬной гипертонией). Целью этой программы являлась оценка эффективности применения ингибитора a-глюкозидаз акарбозы в дозах 150 и 300 мг в сутки и немедикаментозных мероприятий по изменению образа жизни и стереотипов питания на течение АГ, показатели углеводного, липидного обмена и массу тела.АПРЕЛЬ является открытой рандомизированной, выполненной на параллельных группах, многоцентровой программой.Она проводилась в России в 17 исследовательских центрах 10 городов – Москве, Санкт-Петербурге, Волгограде, Екатеринбурге, Краснодаре, Новосибирске, Томске, Тюмени, Уфе и Челябинске.

Артериальной гипертонией (АГ) страдают 15–25% взрослого населения. Наличие АГ существенно влияет на состояние здоровья, продолжительность и качество жизни пациентов, так как заболевание является основным фактором риска развития сердечно-сосудистых осложнений. Подобно головному мозгу и почкам, сердце участвует в патогенезе АГ и одновременно является органом-мишенью. Наиболее частыми изменениями сердца при АГ являются гипертрофия левого желудочка (ГЛЖ), которая встречается у 25–30% больных АГ и диастолическая дисфункция левого желудочка (ЛЖ). Доказано, что ГЛЖ при АГ является независимым фактором риска сердечно-сосудистой заболеваемости и смертности, а также основным доклиническим проявлением поражения сердечно-сосудистой системы, которое повышает риск ишемической болезни сердца (ИБС) и инфаркта миокарда, инсульта и застойной сердечной недостаточности, внезапной смерти и общей смертности [1–9]. По данным Корнельского и Фрамингемского исследований, при наличии ГЛЖ риск смертельных и несмертельных осложнений повышается в 2–4 раза независимо от возраста, пола и других факторов риска [4, 8]. Частота выявления ГЛЖ у больных АГ повышается с возрастом (от 6% в возрасте до 30 лет до 43% после 70 лет), встречается у 23–33% лиц старше 59 лет [1] и у 23% у мужчин и 33% женщин старше 59 лет [10]. Кроме того, частота выявления ГЛЖ зависит от тяжести АГ (от 20% при мягкой до 50% и более при тяжелой) и применяемого метода исследования: от 7% по данным электрокардиографии (ЭКГ) до 45% по данным эхокардиографии (ЭхоКГ) и 70% магнитно-резонансной (МР) и вентрикулографии [11–14]. ЭхоКГ является более точным неинвазивным методом определения массы миокарда левого желудочка (ММЛЖ), чем традиционные методы. Данные о ММЛЖ, полученные ЭхоКГ-методом тесно коррелируют с данными аутопсии [14]. ЭхоКГ позволяет не только выявлять ГЛЖ, но и следить за ее динамикой при лечении АГ [4, 15, 16]. Считается, что метод ЭхоКГ дает 10% погрешность в измерении индекса ММЛЖ (ИММЛЖ), поэтому достоверной динамикой ИММЛЖ на фоне лечения могут считаться только изменения более 10%. Требования к антигипертензивной терапии включают в себя достижение целевого уровня артериального давления (АД) и обеспечение протективного действия на органы-мишени. Таким образом, оптимизация лечения больных АГ, ставящая своей целью не только снижение АД, но и органопротекцию с применением современных антигипертензивных препаратов, остается актуальной задачей. Цель исследования: оценить эффективность и переносимость монотерапии моэксиприлом (моэкс, “Schwarz Parma AG”, Германия) в дозе 7,5–15 мг/сут или в комбинации его с гидрохлортиазидом (ГХТ) в дозе 12,5–25 мг/сут у пациентов с мягкой и умеренной АГ, имеющих ГЛЖ во время активного лечения в течение 52 нед.

Aim. To study an antioxidant action of antioxidant vitamins (vitamins С, Е and provitamin A) in vitro and in vivo. Material and methods. The study was made of kinetic parameters of copper-initiated free radical oxidation (FRO) of low density lipoproteins (HDLP) in human blood plasm, antioxidant potential of rat liver and myocardium, the level of FRO products in HDLP and activity of glutathione peroxidase in erythrocytes of 31 males aged 40-64 years with coronary heart disease (CHD). Results. An antioxidant action of the combinations alpha-tocopherol+ascorbic acid and alpha-tocopherol+beta-carotin was much more potent than that of each of the component alone. The whole complex of the antioxidants completely suppressed FRO of HDLP in the model system. Feeding rats for 30 days with a complex of antioxidant vitamins and selenium produced a sharp enhancement of the antioxidant potential of the liver and a complete suppression of free radical processes in the myocardium. If this complex was given to CHD patients for 2 months, it sharply reduced the amount of FRO primary and secondary products in blood plasm LDLP in growing activity of erythrocytic selenium-containing glutathione peroxidase. Conclusion. The scheme is proposed for objective experimental assessment of antioxidant efficacy of multicomponent antioxidant medication in laboratory and clinical trials.

От имени исследовательской группы:Мы выражаем глубокую благодарность всем соисследователям, принимавшим участие в исследовании РОСА: Арутюнову Г.П., Абросимову В.Н., Барбараш О.Л., Бартошу Л.Ф., Волковой Э.Г., Воронину И.М., Габинскому Я.Л., Галявичу А.С., Гапон Л.И., Гельцеру Б.И., Дембицкой А.Ф., Довгалевскому П.Я., Закировой А.Н., Ивлевой А.Я., Кательницкой Л.И., Космачевой Е.Д., Крюкову Н.Н., Лопатину Ю.М., Мартюшову С.И., Мордовину В.Ф., Нечаевой Г.И., Никитину Ю.П., Останиной О.Н., Уринскому М.Е., Фомину И.В., Фурменко Г.И., Хохлову А.Л., Хрусталеву О.А., Чумаковой Г.А., Шляхто Е.В., Щекотову В.В., Якушину С.С., а также всем врачам, участвовавшим в исследовании. Национальный координатор исследования акад. РАМН, член-корр. РАН Юрий Никитич Беленков, главный исследователь Ирина Евгеньевна Чазова, ответственный исполнитель Людмила Геннадьевна Ратова. Цель исследования Целью исследования РОСА стало сравнение эффективности, безопасности и влияния на частоту развития сердечно-сосудистых осложнений у больных АГ двух тактик лечения: применения алгоритма ступенчатого назначения 4 классов антигипертензивных препаратов в группе интенсивного лечения и произвольной антигипертензивной терапии в группе стандартного лечения. Задачи исследования: • Изучить возможность достижения целевого уровня АД [

От имени исследователей - Соисследователи: Аметов А.С., Архипов М.В., Батурин А.К., Волкова Э.Г., Глезер М.Г., Горностаев В.В., Закирова А.Н., Ивлева А.Я., Карпов Р.С., Комиссаренко И.А., Кошельская О.А., Кривозубов Е.Ф., Лазебник Л.Б., Медведева И.В., Мезенцева Н.Г., Недогода С.В., Ратова Л.Г., Соколова Л.А., Спиропулос Н.А., Фурсов А.Н., Чорбинская С.А.,Шестакова М.В. - Проведение программы АПРЕЛЬ было инициировано отделом системных гипертензий НИИ кардиологии им. А.Л.Мясникова РК НПК МЗ и СР РФ под руководством проф. И.Е. Чазовой. Программа стартовала в ноябре 2003 г. и завершилась в июле 2004 г. Она проводилась в Москве и ряде регионов России: Центральном, Северо-Западном, Южном, Поволжье, Уральском, Западной Сибири и республике Башкортостан. В программе принимали участие 17 исследовательских центров из 10 городов России: Москвы, Санкт-Петербурга, Волгограда, Екатеринбурга, Краснодара, Новосибирска, Томска, Тюмени, Уфы, Челябинска. Основанием для проведения программы АПРЕЛЬ послужила широкая распространенность метаболического синдрома (МС), основными проявлениями которого являются абдоминальное ожирение, нарушения углеводного, липидного обмена и артериальная гипертония (АГ).результаты Российского исследования АПРЕЛЬ продемонстрировали, что акарбоза (глюкобай) позитивно воздействует на основные факторы сердечно-сосудистого риска – избыточную массу тела, постпрандиальную гипергликемию и АГ. Снижение массы тела, уровня постпрандиальной гликемии и АД на фоне монотерапии акарбозой суммарно снижает степень риска развития сердечно-сосудистых осложнений, что ранее доказано результатами исследования STOP-NIDDM.Акарбоза обладает уникальным механизмом периферического действия, т.е. способностью препятствовать всасыванию углеводов на уровне тонкой кишки. Периферическое действие акарбозы и отсутствие системного действия определяет ее безопасность для больных МС, т.е. больных с множественными сердечно-сосудистыми факторами риска.Благодаря своей безопасности, способности снижать АД и постпрандиальный уровень глюкозы, не вызывая при этом гиперинсулинемию, а также эффективно уменьшать массу тела, акарбоза может применяться в качестве монотерапии у больных с ожирением, мягкой АГ и нарушениями углеводного обмена.

Aim. To study effectiveness of various types of coronary stenting in bifurcation stenoses. Material and methods. Fifty six patients with bifurcation stenoses were divided into 2 groups: stenting of the basic and side branch of the coronary artery (CA) was made in group 1 patients (n = 27), stenting of the basic branch and balloon angioplasty of the side branch were made in group 2 (n = 29). Primary clinical and angiographic response reached 96 and 90% in groups 1 and 2, respectively. Complications were absent in group 1, occurred in 13.7% cases in group 2 (the difference was insignificant). One year after the procedure lethal outcomes were absent. The number of unfavourable clinical outcomes was higher in group 1 (25.9 and 13.7%, respectively, p = 0.4). The rate of restenoses detected angiographically was not significantly different in group 1 and 2 (33 and 26%, respectively). Conclusion. Stenting of bifurcation stenoses brings about good short-term and satisfactory long-term results in most of the patients. The rate of the complications was low. Two stents implantation (in basic and side branches) has no significant advantages over stenting of the basic CA and balloon angioplasty of its side branch.

Aim. An open non-randomized trial was initiated to assess clinical and angiographic results of using the coronary stent "Ephesos" in 457patients with stable or unstable angina pectoris and native coronary affections. Material and methods. 268 stents have been implanted in 231 patients with stable angina (SA) and 271 stents - in 226 patients with unstable angina (UA). 46% lesions were complicated. The length of stenosis was 12.9 ± 6.7 mm in the group SA and 14.1 ± 7.4 mm in the group UA, 30%? stenoses were long. Results. Successful stenting was stated in 99%, without cases of acute thrombosis. Non-fatal myocardial infarction took place in hospital in 1.3% of SA patients and in 2.6% of UA patients. Incidence of cardiac complications (death, recurrent angina pectoris, myocardial infarction, restenosis, repeated revascularization) for 6-month follow-up was 15.6% in SA group and 18.1% in UA group. At angiographic control, the index of vascular diameter loss made up 0.22 ±0.2 in SA group and 0.3 ± 0.27 in UA group. Incidence of restenosis was 12 and 14%, respectively. 18-month follow-up found no differences in frequency of complications: 21.6 and 22.6%, in groups SA and UA, respectively. Conclusion. Implantation of the stent "Ephesos" is effective in prevention of thrombosis and restenosis in patients with stable or unstable angina pectoris at high risk of intervention.

Aim. To study the changes of the levels of cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (hsTnI)) in patients with newly diagnosed multiple myeloma (MM) during programmatic treatment with bortezomib (VCd regimen).Material and methods. This prospective pilot study included patients with a newly diagnosed MM (n=30), who were scheduled for a cycle of chemotherapy including a proteasome inhibitor (bortezomib). All patients underwent standard laboratory (complete blood count, biochemical tests, serum protein electrophoresis), electrocardiography, echocardiography, as well as the level of specific laboratory markers of myocardial dysfunction (NT-proBNP) and injury (hsTnI) was determined immediately before treatment, after 3 and 6 cycles of chemotherapy.Results. The mean age was 63,8±10 years with a slight predominance of men (56,7%, n=17). The patients initially had an increased level of NT-proBNP (316 [75,9; 602,6] pg/mL) with its decrease to 144,0 [102,3; 294,0] pg/ml after 3 cycles and to 109,2 [59,9; 344,5] pg/ml after 6 cycles of chemotherapy. At the MM onset, the mean hsTnI values were 0,06 [0,03; 0,49] ng/mL, whereas after 3 and 6 chemotherapy cycles it accounted for 0,02 [0,01-0,68] and 0,65 [0,02; 1,51] ng/ml, respectively, with the normal range of less than 0,1 ng/ml. Despite this, no statistical significance has been obtained. There were no clinical and/or laboratory signs of heart failure, ischemia, or other non-cardiac causes of elevated NT-proBNP levels in this cohort. Multivariate regression analysis revealed the following significant factors influencing the initial hsTnI level: paraprotein, hemoglobin and erythrocyte sedimentation rate (ESR). The resulting regression model was characterized by a strong correlation (r=0,702, p

Aim. To study the levels of pro-inflammatory biomarkers in patients with obstructive and non-obstructive coronary artery disease (CAD), to identify possible differences for diagnosing the degree of coronary obstruction.Material and methods. The observational study included two groups of patients: with non-obstructive (main group, coronary artery stenosis

Aim. To study the levels of fibrosis markers in patients with stable coronary artery disease (CAD) and various types of coronary artery (CA) lesions (obstructive and non-obstructive), to identify possible differences for diagnosing the types of coronary obstruction.Material and methods. The observational study included three groups of patients: with non-obstructive (main group, coronary artery stenosis 0.05). There were no statistically significant differences in TGF-β1 levels depending on the type of left ventricular remodeling (p=0.139). The maximum level of MMP-9 was in the group with obstructive coronary disease and significantly differed from the main group (p

In patients with coronary artery disease (CAD) and those who suffer from second type diabetes mellitus micro vascular disorders was found. Diabetes is associated with an increased risk of cardiovascular events. It might be due to micro vascular changes. We hypothesized that patients with CAD and CAD with diabetes mellitus (CAD DM) have differences in structural and functional condition of microcirculation. We studied 50 patients with CAD, 43 CAD DM patients and 34 healthy controls. Digital photoplethysmography, computer nail fold videocapillaroscopy at baseline, after postocclusive hyperemia and during venous congestion were performed. We evaluated functional (occlusion index (IO)) and structural disorders (refl ection index (RI,%) of arterioles. The structure of coetaneous capillaries by capillary density (CD, cap/mm2) was assessed. Capillary function was estimated by percent perused capillaries (pPC,%). CAD and CAD DM patients had structural and functional changes of microcirculation. RI, IO and pPC in CAD and CAD DM patients were significantly different from controls (p0.6). CD in CAD DM group was significantly lower than in CAD and control groups (p< 0.019). The results show a decrease of micro vascular function in both CAD and CAD DM patients. CAD DM patients have also structural changes in capillary level.

Neuregulin-1β (NRG-1) is an emerging biomarker of heart failure (HF). The mechanisms of its action in HF patients are yet to be investigated. Cardioprotective and anti-inflammatory effects of NRG-1 have been reported.Aim. To assess NRG-1 levels in HF patients and investigate the association between NRG-1 and biomarkers of inflammation and myocardial fibrosis.Material and Methods. NRG-1, biomarkers of inflammation and fibrosis (hsCRP, IL-6, sVCAM-1, MMP-9, Galectin-3, ST2, TGF-β) were assessed in 47 patients with HF and preserved ejection fraction (HFpEF); 39 patients with HF and reduced ejection (HFrEF) and 40 healthy participants. The associations between NRG-1 and biomarkers of inflammation and fibrosis, as well as the composite outcomes of cardiovascular death and HF hospitalisations were assessed.Results. Median NRG-1 levels in HFpEF were 0.969 (0.348; 1.932) ng/ml, in HFrEF – 0.63 (0.348; 1.932), in healthy participants 0.379 (0.195; 0.861) ng/ml, and was significantly higher in HFpEF compared to healthy volunteers (р=0.004). There was no difference in NRG-1 concentration between HFpEF and HFrEF. In HF patients, all biomarkers of inflammation and fibrosis were higher than in controls. ST2, IL-6 and TGF-β were significantly higher in HFrEF compared to HFpEF patients, while hsCRP, sVCAM-1, MMP-9, and Galectin-3 levels were comparable. In HFpEF, NRG-1 was associated with hsCRP (rs=0.378, p=0.023) and IL-6 (rs=0.378, p=0.014). Median follow-up time in patients with HFpEF and in patients was 312 (236; 388) days, in HFrEF – 147 (98; 237) days. In HFpEF, 2 patients died and 19 were hospitalized due to HF. In HFrEF, 10 deaths and 19 hospitalizations were registered. Kaplan-Mayer analysis showed that HFpEF patients with increased NRG-1 and IL-6 had higher levels of HF hospitalisation (log rank test, р=0.046 and р=0.012, respectively). In a multivariable cox proportional hazard model, the association between the NRG-1 and outcomes remained significant after adjustment for age, gender and NTproBNP but diminished when hsCRP and IL-6 were included in the model.Conclusion. NGR-1 level significantly higher in HFpEF compared to healthy participants, and comparable with NRG-1 concentrations in HFrEF. In HFpEF, NRG-1 was associated with biomarkers of inflammation and fibrosis. The prognostic value of NRG-1 in HF requires further investigations.

Aim. To assess the structure and performance of left atrium (LA) before and after 3 cycles of anticancer treatment in lymphoma patients, as well as the incidences of supraventricular arrhythmia (SVA) and the levels of biomarkers of inflammation.Material and Methods. This is a prospective observational study of patients with confirmed diagnosis of lymphoma [n=23; 57% men; median age 52 (34;64) years], who had no prior polychemotherapy. The comparison group included persons without lymphoma [n=18; 50% men; median age 43 (37; 54) years] comparable with the main group in terms of sex, age and risk factors for cardiovascular diseases. Patients with lymphoma underwent 24h-ECG monitoring and advanced transthoracic echocardiography at baseline and after 3 cycles (within 3 months) of anticancer treatment. Biomarkers of inflammation were measured. The results were compared with the data of the comparison group.Results. In lymphoma patients, LA reservoir, conduit, and booster function were found to be impaired at baseline but were comparable with these in matched controls. After 3 cycles of anticancer treatment, a trend to reduction of LA booster and conduit strain was found. The proportion of those with SVA was significantly higher in lymphoma patients before chemotherapy compared to those after anti-cancer treatment or controls: 57% vs 10% and 33% respectively (p

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p

Aim. To study the effect of enhanced external counterpulsation (EECP) on the functional status, quality of life, structural and functional state of the vascular bed, and markers of glycemic control in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM).Material and methods. A pilot prospective randomized study included 30 patients with CAD and DM. Using a random number generator, patients were randomized into 2 groups: EECP (n=15) and a comparison group (n=15). All patients (n=30) received optimal medical therapy (OMT) during 3 months of follow-up. Patients in the EECP group underwent a course of EECP (35 hours, cuff pressure: 220-280 mmHg) during the first 7 weeks of the study. At baseline and after 3 months of follow-up, patients in both groups underwent an assessment of clinical status, quality of life (based on the SF-36 questionnaire), as well as a 6-minute walk test to assess exercise tolerance. The dynamics of fasting glucose, postprandial glucose, insulin resistance index (HOMA-IR) and glycated hemoglobin were assessed. Photoplethysmography and applanation tonometry were performed to assess the state of the vascular bed.Results. In the EECP group, after 3 months, there was a decrease in the frequency of angina attacks and an improvement in the functional class of angina according to the Canadian Cardiovascular Society (CCS) classification. A significant improvement in exercise tolerance was revealed [an increase in the 6-minute walking distance by 51 (35; 65) m, p0.05), with the exception of the reflection index and the stiffness index (p

Aim. To investigate on post-COVID period in patients of the Eurasian region.Material and methods. A total of 9364 consecutively hospitalized patients were included in ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.Results. According to ACTIV register, 63% of patients after COVID-19 had new adverse symptoms or exacerbations of the existing symptoms lasting for up to 1 year. After hospital discharge, 79,8% of patients sought unscheduled medical attention in the first 3 months, 79,1% at 4-6 months, and 64,8% at 7-12 months. Readmission rate was 11,8% in the first 3 months, 10,9% at 4-6 months, and 10,1% at 7-12 months. The most common reasons for unscheduled treatment in the first 3 months were uncontrolled hypertension, decompensated type 2 diabetes, destabilization of coronary artery disease, gastrointestinal disease, AF episodes, exacerbation of asthma and chronic obstructive pulmonary disease, decompensated heart failure (HF). The 12-month mortality of COVID-19 survivors after the discharge was 3,08%. Multivariate analysis showed that independent risk factors for fatal outcome were age (direct correlation), the levels of hemoglobin (inverse correlation), oxygen saturation (inverse correlation), and aspartate aminotransferase (direct correlation), as well as class III-IV HF, prior stroke, cancer, inhospital acute kidney injury. Based on these identified risk factors, a nomogram was constructed to determine the 3-month mortality risk after discharge.Conclusion. Analysis of ACTIV register showed that end of the acute phase of COVID-19 does not imply a complete recovery.

Aim. To determine the median levels of neuregulin-1 (NRG-1; endothelium-derived growth factor and the natural agonist of the ERBB3 and ERBB4 receptors) NRG-1 in healthy volunteers and to study the associations of NRG-1 levels with gender and age.Material and Methods. Ninety seven healthy participants were enrolled (median age of 44 [32-54], men 45 men [46.4%]). The following age groups were identified: 20-29 y.о. (n=20, men – 50.0%), 30-39 y.о. (n=21, men – 52.4%), 40-49 y.о. (n=22, men – 45.5%), 50-59 y.о. (n=22, men – 36.4%); 60-69 y.о. (n=12, men – 50.0%). Peripheral blood samples were collected at the time of enrolment, standard laboratory tests were performed, and NRG-1 levels were determined in the plasma samples by ELISA.Results. In the cohort of 97 healthy participants the median value of NRG-1 was 0.3 [0.121-2.24] ng/ml. NRG-1 levels did not differ significantly between men and women (p=0.145), indicating that NRG-1 levels are not influenced by gender. The levels of NRG-1 were similar in the different age groups: age 20-29 years=0.26 [0.17-0.37] ng/ml; age 30-39=0.24 [0.1-0.39] ng/ml; age 40-49=0.31 [0.19-1.15] ng/ml; age 50-59=0.37 [0.19-1.0] ng/ml; age 60-69=0.4 [0.13-0.81] ng/ml. Correlation analysis between NRG-1 levels and route blood measurements (haemoglobin, lipids, glucose, creatinine, and uretic acid) did not show significant associations.Conclusions. In this study, the median value of NRG-1 plasma levels were determined. The results of the study show that age and gender had no influence on NRG-1 values.

Aim. An appraisal of practitioners with chronic constipation management details in older and senile adults.Key points. Chronic constipation is a common issue in geriatrics. Aside to age-related physiological bowel disfunction, a higher constipation incidence is conditioned by declined physical activity and frailty, polypharmacy and a series of secondary constipation-developing chronic states and diseases. Chronic constipation is associated with a higher risk of cardiovascular disease and complications, impaired general perception of health and pain, growing alarm and depression, and reduced quality of life. The treatment tactics in chronic constipation is cause-conditioned and should account for the patient’s history and therapy line, overall clinical condition, cognitive status and functional activity level. An essential baseline aspect of constipation management is apprising the patient and his family of the underlying factors and methods for non-drug and drug correction. An higher-fibre diet is recommended as first measure, with osmotic laxatives added and titrated to clinical response if none observed towards the non-drug and high-fibre regimens. Stimulant laxatives and prokinetics should be recommended in patients reluctant to fibre supplements and osmotic laxatives. Subsidiary correction includes biofeedback, transanal irrigation, acupuncture, foot reflexology and percutaneous tibial nerve stimulation.Conclusion. Elderly and senile chronic constipation is a prevalent multifactorial state requiring an efficient management via assessment and correction of total risk factors and consistent use of non-medication and drug therapies.

Aim. To study the mid-term effects of enhanced external counterpulsation (EECP) in the structural and functional parameters of blood vessels, exercise tolerance and quality of life indicators in patients with verified coronary artery disease (CAD).Material and methods. Patients (n=70) with verified stable CAD (angina pectoris class II-III) complicated by chronic heart faillure class II-III (NYHA) were included in the study. Data from 65 patients (48 to 74 years old; 45 men and 20 women) are included in the final analysis. All patients had a course of EECP (35 hours procedures with a compression pressure of 220-280 mm Hg). All patients at baseline, 3 and 6 months later had a 6 walk minute test (6WMT), an assessment of the clinical status, quality of life of patients (Minnesota Living with Heart Failure Questionnaire, SF-36). Computer nailfold video capillaroscopy, photoplethysmography with pulse wave recording and contour analysis, applanation tonometry to assess central aortic systolic pressure and radial augmentation index were performed to assess the structural and functional state of large and microcirculatory vessels.Results. Significant improvement in exercise tolerance both after 3 and after 6 months (increase in distance in 6WMT by 44.6% after 3 months and 34.3% after 6 months, p

Aim. To study the level of serum biomarkers of endothelial dysfunction and myocardial stress in patients with various types of hypertrophic cardiomyopathy (HCM).Material and Methods. 48 patients with hypertrophic cardiomyopathy (27 men and 21 women) were examined, the mean age was 54±13 years. The patients were divided into two groups according to the course options: group 1 - symptomatic stable course (n=14); group 2 - progressive course of symptomatic HCM (n=34). In accordance with the assigned tasks, all patients underwent determination of biological markers of neurohumoral systems in blood serum using immunofluorescence assay analysis: N-terminal fragment of brain natriuretic peptide (NT-proBNP), von Willebrand factor (vWF), endothelin-1, E-selectin with subsequent evaluation and correlation of results with clinical and instrumental characteristics of patients. When performing echocardiography following parameters were assessed: dimensions of the heart chambers, the thickness of the interventricular septum, the thickness of the posterior wall of the left ventricle (LV), LV mass, LV mass index, the ratio between LV filling in diastole (peak E) and atrial systole (peak A)-(E/A), relative myocardial thickness index, left atrial volume index.Results. Both groups showed increased levels of NT-proBNP and endothelin-1. E-selectin and vonWillebrand factor remained within the normal range. There was no statistically significant intergroup difference. There was a correlation between the level of the index of the relative myocardial thickness and the level of NT-proBNP (r=0.30; p=0.04). A correlation was found between the level of the vWF marker and the left atrial volume index (r=0.32; p=0.04). When assessing the association of indicators of intracardiac hemodynamics with other markers (E-selectin and endothelin-1, no statistically significant relationships were found.Conclusion. In the course of the research, it was found that the high activity of endothelin-1 and NT-proBNP reflects endothelial dysfunction and myocardial stress in patients with HCM, especially in patients with a progressive variant of HCM. However, we did not find any changes in the levels of E-selectin and von Willebrand factor, as well as their intergroup differences. These results require additional studies to assess endothelial dysfunction in patients with HCM.

Heart failure with preserved ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Little progress has been in the treatment of this condition since its introduction some 30 years ago. It's accepted that HFpEF is heterogeneous in many ways, ethologically and phenotypically. The underlying mechanisms of the syndrome are not clear. Recently, it has been shown that the diagnostic criteria for HFpEF lacks sensitivity and specificity. Novel treatment approaches, which were developed based on current HFpEF pathophysiological concepts, did not show either clinical or prognostic benefit for patients. Therefore, there is an urgent need to revise current diagnostic approaches and to further investigate the underlying mechanisms. Recently, two novel diagnostic score systems were proposed: H2PEF and HFA-PEFF. Recently, a number of phase II and III randomized control trials have been completed. Here, the authors discuss the potential novel diagnostic approaches to HFpEF and treatment perspectives.

Aim. To study the lipid profile in hospitalized patients with coronavirus disease 2019 (COVID-19) depending on the outcome of its acute phase according to the AKTIV international registry.Material and methods. The AKTIV registry included men and women over 18 years of age with a diagnosis of COVID-19, who were treated in a hospital. A total of 9364 patients were included in the registry, of which 623 patients were analyzed for levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides on days 1-2 of hospitalization. The level of high-density lipoprotein cholesterol (HDL-C) was calculated using the Friedewald equation.Results. We found that a decrease in LDL-C level was significantly associated with an unfavorable prognosis for hospitalized patients with COVID-19. This pattern persisted in both univariate and multivariate analyses. LDL-C levels in the final multivariate model had a significant relationship with the prognosis (an increase in the death risk by 1,7 times with a decrease per 1 mmol/l). In addition, we found that the survival of patients with an indicator level of

Aim. To assess the relationship between fibrosis markers and structural and functional parameters in patients with various types of hypertrophic cardiomyopathy (HCM).Material and methods. This prospective comparative non-randomized study included 49 patients with HCM. Patients were divided into 3 groups according to the disease course: group 1 — stable course (n=12; men, 8 (67%), mean age ‒ 41±12 years); group 2 — progressive course (n=26; men, men, 16 (61%). mean age — 57±11 years); group 3 — patients with atrial fibrillation (AF) (n=11; men, 4 (36%), mean age — 63±6 years). Patients underwent standard clinical and paraclinical investigations. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were determined in all patients using enzyme-linked immunosorbent assay in blood serum.Results. In all patients with HCM, elevated levels of MMP-9 and TIMP-1 are noted compared to the reference values. In group 1, the MMP-9 level [Me (Q1; Q3)] was 226 (201;271) ng/ml; TIMP-1 — 410 (267;488) ng/ml; in group 2, the MMP-9 level was 236 (187;285) ng/ml; TIMP-1 — 421 (321;499) ng/ml. In the course with AF, the MMP-9 level was 260 (228;296) ng/ml, while TIMP-1 — 381,5 (305;466) ng/ml; no significant difference was revealed (p=0,59; p=0,90, respectively). A correlation was found between age and MMP-9 levels, as well as between MMP-9 levels and left atrial volume (p=0,034; p=0,035, respectively).Conclusion. The high activity of matrix metalloproteinases and their tissue inhibitors reflects enhanced fibrosis and myocardial remodeling in HCM, which is especially characteristic of patients with AF.

The prevalence of coronary heart disease (CHD) and type 2 diabetes mellitus (type 2 diabetes) in Russia and in the world continues to increase. Despite the prevention and optimization of therapy, CHD retains its leadership among all causes of death, and the mortality rate from type 2 diabetes and its complications gradually increases too. To improve the treatment of the above mentioned diseases, it is necessary to clarify the pathogenetic mechanisms of their development. The formation of endothelial dysfunction, characterized by an increase in the level of cell adhesion molecules and vasoconstriction, is a common link characteristic for the course and progression of CHD and type 2 diabetes. This article presents an analysis of preand clinical studies on the role of endothelial dysfunction markers: cell adhesion molecules (E-selectin), vasoconstriction (endothelin-1) and von Willebrand factor in patients with CHD, including those with type 2 diabetes mellitus.

Aim. To study the effect of multiagent chemotherapy on structural and functional vascular, electrophysiological parameters and cardiac hemodynamics in patients with stomach cancer.Material and methods. The study included 3 groups of 25 people: healthy volunteers, those with established cardiac disease (hypertension + coronary artery disease), gastric adenocarcinoma (fluoropyrimidine/platinum-based chemotherapy). Cancer patients before and after chemotherapy courses underwent non-invasive assessment of vascular wall and endothelial dysfunction (videocapillaroscopy, digital photoplethysmography), as well as electrocardiography and echocardiography. Healthy volunteers and cardiac patients were examined once.Results. In cancer patients, even before chemotherapy courses, endothelial dysfunction (ED) (occlusal index, 1,7 (1,4; 1,9), normal values >1,8) and structural vascular disorders (stiffness index, 8,9 m/s (7,7; 9,7), normal values

Aim. To study some vascular remodeling markers in hypertensive patients depending on the presence of type 2 diabetes mellitus.Material and methods. The study included patients with essential hypertension 1-2 degrees of increase in blood pressure with/without type 2 diabetes (30 and 32 patients respectively). Using photoplethysmography in combination with reactive hyperemia test structural and functional markers of vascular remodeling were determined: in large vessels – stiffness index and phase shift; in microvessels – reflection index and the occlusion index. Using the computer video capillaroscopy of the nail bed the density of the capillary network at rest, after venous occlusion and after the test with reactive hyperemia was determined. ELISA was used for determining the level of humoral markers of endothelium dysfunction and vascular bed remodeling: metalloproteinase 9, metalloproteinase 9 inhibitor, E-selectin, endothelin, transforming growth factor (TGF-β1), endothelial growthfactor A.Results. In compare with hypertensive patients in hypertensive patients with type 2 diabetes significantly higher stiffness index values (11.15 [10.05; 12.35] vs 10.15 [8.83; 11.83] m/s; p=0.04) were found as well as significantly lower (p=0.00) capillary network density at rest (26.4 [24.2; 27.6] vs 35.1 [33.0; 45.0] cap/mm2; p=0.00) after the tests with reactive hyperemia (29 [24; 33.3] vs 40.0 [35.0;43.3] cap/mm2; p=0.00) and venous occlusion (32.5 [27.8; 34.5] vs 40.0 [33.0; 45.0] cap/mm2). In hypertensive patients with type 2 diabetes significantly higher levels of TFG-β1 (11648 [4117.8; 37933.8] vs 3938.5 [1808.8; 7694] pg/ml; p=0.00) and significantly lower levels of endothelin-1 (0,46 [0,29;1,3] vs 1.73 [0.63; 2.30] ng/ml; p=0.01) was detected in compare with hypertensive patients without type 2 diabetes.Conclusion. In both groups some signs of vascular remodeling were found at the level of both large arteries and microvessels (arterioles and capillaries). However, the group of hypertension + type 2 diabetes mellitus had statistically significantly more pronounced changes in arterial stiffness, capillary network density, as well as humoral markers levels of fibrosis and endothelial dysfunction.

Obesity is one of the leading and the most serious risk factors of cardiovascular diseases. Overweight provokes many metabolic and hemodynamic disorders. About 30% of inhabitants of the planet have overweight and prevalence of obesity increases by 10% every 10 years according to the WHO data. The probability of arterial hypertension in obese patients is 50% higher than in people with normal body mass. Framingham study showed that obesity is an independent, significant risk factor of ischemic heart disease, myocardial infarction, cerebral stroke and diabetes mellitus. The most dangerous is the central obesity with the preferential fat deposition in the abdomen. Combination of visceral obesity, violation of carbohydrate and lipid metabolism, arterial hypertension, and close pathogenic relationship between these factors underlie the isolated symptom complex known as metabolic syndrome. J. Vague was the first to describe relationship between abdominal obesity with cardiovascular disease and mortality in 1947. In our country G.F. Lang noticed common combination of arterial hypertension with obesity, lipid and carbohydrate metabolism disorders. Thus, metabolic syndrome significantly increases risk and severity of cardiovascular disease. Within last decades criteria of metabolic syndrome stays constant. The factors of insulin resistance and endothelial dysfunction as stages of the pathogenesis of the metabolic syndrome have been studied in detail. The mechanisms of insulin resistance and endothelial dysfunction are discussed in detail in this article as well as inflammatory markers and the significance of highly sensitive C-reactive protein.

Possibilities and prospects for the clinical use of enhanced external counterpulsation (EECP), which has long established itself throughout the world, are discussed in the article. Historical background, as well as the development stages of EECP for the treatment of patients with coronary heart disease (CHD) and chronic heart failure (CHF) are considered. The mechanism of action of the EECP and the main hemodynamic, neurohumoral and tissue effects that justify its use are presented. The effect of EECP on endothelial function and coronary reserve, disorders of which occurs in the majority of cardiovascular diseases, is considered separately. Treatment of patients with CHD, including complicated by CHF, are the most studied indications for EECP using in medical practice. The evidence base for treatment of patients with these disorders by EECP is presented in the article. Prospects for the EECP application in other areas of medicine are also presented.

Aim. To study the structure of co-morbidities, especially connective tissue undifferentiated dysplasia syndrome (CTDS), in patients with hypertrophic cardiomyopathy (HCM) to develop an algorithm of complex examination of patients.Material and methods. Patients with HCM (n=186; 88 men and 78 women) were examined. The diagnosis of HCM was based on current guidelines; molecular genetic study was performed in the absence of phenotypic manifestations. Echocardiography and standard examination of cardiac patient were performed in all patients to identify comorbidities. Genotyping of polymorphisms of 12 modifying genes was performed in 61 patients and 61 people in the control group.Results. HCM was most often associated with uterine myoma (52%), cardiac and extracardiac congenital malformations (50%), and thyroid diseases (37%). Combination of HCM with different variants of connective tissue dysplasia was found in 17% of patients (mitral valve prolapse – 6.3%, tricuspid valve prolapse – 2.7%, supplemental chords – 4.5%, bivalve aortic disease – 1.8%, increased left ventricular trabeculation – 3.6%, atrial septal aneurysm – 3.6%, membranous ventricular septal defect – 1.8%).Conclusion. CTDS is one of the most often associated disorders in patients with HCM. The study of the association of CTDS and HCM, the nature of their genetic structure and similarity of pathogenesis require further study.