IMMUNOPATHOGENESIS OF HEART FAILURE IN PATIENTS WITH INFECTIVE-IMMUNE MYOCARDITIS

Aim. To study quantitative parameters, specifics of functional state of the main subpopulations of peripheral blood lymphocytes of the infective-immune myocarditis patients (IIM) and postmyocarditis cardiosclerosis (PMC), and specifics of cytokine profile.Material and methods. Totally, 35 IIM patients included, and 39 with PMC. In 17 patients with IIM there was significant heart failure (HF) — III functional class (FC) by New-York Heart Association (NYHA), in 18 patients with IIM there were no signs of HF, or mild signs (0-II FC by NYHA). In 18 patients with PMC there were no signs of HF, and in 21 — there was I FC by NYHA. The controls were 10 formally healthy persons. Study of population and subpopulation contents, and lymphocytes activation markers of peripheral blood, was done with four-color laser flow cytometry using FACSCalibur equipment and relevant monoclonal antibodies (Beckton Dickinson, USA). We studied the mean cytokines concentrations characterizing Th1-, Th2- and Th17- subpopulations of the helper lymphocytes. Measurement of serum cytokines was done with the method solid-phase immune-enzyme assay with LLC “Vectro-Best” (Russia) media. Statistics was done with software PASW Statistics 18.Results. Inflammatory diseases of myocardium show the deviations of native, as acquired immunity. In IIM and PMC there was significant decrease of NKTlymphocytes, not related to the severity of HF signs and durations of the disease. Immunity activation signs in IIM group showed the increase of the early activator marker CD25 expression activation, that was marked during the first 2 weeks from the disease onset. Following, by the end of the 1st month and on the 2nd month from the disease onset, the increase of T- and non-T-lymphocytes was found with the signs of delayed activation, revealed by HLA-DR antigen expression. The activator marker patterns were differ in patients with different grade of HF severity. Concentration of interferon-γ (IFN-γ) and interleukine (IL)-4 was more than 3 times higher in IIM patients comparing to controls. There was more than 7-times higher increase of IL-17A, and concentrations of effectory cytokines of Th17-subpopulation — IL-8 and granulocyte-macrophagal colony-stimulating factor (GM CSF). The level of IFN-γ reached maximal levels during the first 2 weeks from the disease onset. Later, IFN-γ concentration declined. Opposite, serum level of IL-4 was significantly increased by the end of the 1st and on the 2nd month from disease onset. Concentrations of IL-17A, IL-8 and GM CSF in blood serum were increased during the whole 2nd week, by the end of the 1st month and on the 2nd month. Th17-cytokines concentrations were significantly increased in PMC patients. Level of IL-17A was higher than in controls almost two times, IL8 — by 51%, GM CSF — by 50%. Serum levels of IL-4, and IL-17A, IL-8 and GM CSF were higher in subgroup of PMC patients with the disease duration less than 6 months. Conclusion. Disorders of anti-infection immunity and mechanisms of selfrestriction of immune reactions do play important role in development of myocardium damage of inflammatory origin

Controversial and open issues of diagnosis and treatment of myocarditis (based on the discussion of Russian national recommendations)

In October 2020, the Russian Ministry of Health approved clinical guidelines for the management of patients with myocarditis. The aim of this review was to highlight controversial and open issues without unambiguous answer or those that were not described in the paper. The review highlights the objective factors that complicate the development of practical guidelines for the management of this category of patients. Comments on the definition and classification of inflammatory heart diseases are given. The approaches to the diagnosis of patients with suspected myocarditis are discussed. Particular attention is paid to the decision-making strategy in selecting optimal therapy in patients with documented myocarditis and the role of endomyocardial biopsy

Evaluation of the effect of the use of the drug ticagrelor in patients with acute coronary syndrome on achieving the target indicator “reduction of mortality from diseases of the circulatory system” in 2022-2024

Aim. To evaluate the effect of the use of the double antiplatelet therapy (DAT) with ticagrelor compared to DAT with clopidogrel and antithrombotic therapy with acetyl salicylic acid (ASA) in patients with acute coronary syndrome and patients with high coronary risk on the target indicator (CP) of the state program (GP) “Development of Healthcare” and the federal project “Fight against cardiovascular diseases” — reducing mortality from diseases of the circulatory system (BSC).Material and methods. All adult Russian patients with a diagnosis of ACS eligible for DAT were considered as the target population; in the second and third years, only patients with high coronary risk continued treatment. The calculation of the number of deaths that can be prevented using DAT ticagrelor 90 mg + ASA vs DAT of clopidogrel + ASA within 1st year from the date of diagnosis was based on the clinical efficacy data of the PLATO study. The number of deaths that can be prevented with the use of DAT ticagrelor 60 mg + ASA — instead of ASA monotherapy patients with a history of myocardial infarction was made based in the clinical efficacy results of the PEGASUS study. It was calculated what proportion of the target indicators could be achieved in 2022-24 years by using DAT with ticagrelor instead of clopidogrel or ASA monotherapy.Results. The use of DAT with ticagrelor vs DAT with clopidogrel or ASA for the treatment of patients with ACS will prevent additional 5389, 5704 and 6012 deaths in 2022-2024, that will ensure the implementation of the CP “reduction of mortality from BSC” GP “Development of healthcare” in the Russian Federation by 36,9%, 26,0% and 20,6% respectively.Conclusion. The use of DAT with ticagrelor for the treatment of patients with acute coronary syndrome ensure the implementation of the CP “reduction of mortality from BSC” GP “Development of healthcare” in the Russian Federation in 2024 by 20,6%

Sequelae of COVID-19 at long-term follow-up after hospitalization

Aim. To assess long-term sequelae of COVID-19 in hospitalized patients at 3 to 7 months after discharge.Material and Methods. The whole of 700 patients hospitalized to the temporary COVID-19 treatment center hosted by the FSBI “National Medical Research Center of Cardiology” of the Ministry of Health of Russia from April to June 2020 were invited to participate in a follow-up study. At 3-7 months after the index hospitalization, patients or their proxies were contacted via telephone in order to obtain information on their vital status, cardiovascular and other conditions or their complications, and new hospitalizations. In addition, patients were invited to an outpatient visit under the "COVID-19-follow-up" program, encompassing physical examination and a comprehensive battery of laboratory and instrumental tests, including spirometry, chest computed tomography (CT) and the six minute walk test (6MWT). Further, dyspnea was assessed using the mMRC (Modified Medical Research Council) Dyspnea Scale. Results: We were able to contact 87.4% (612/700) of patients or their proxies. At follow-up, 4.4% (27) patients died, of which 96.3% (26) had cardiovascular diseases (CVD). A total of 213 patients aged 19 to 94 years old (mean age 56.8±12.5, median 57 years [49.0; 64.0]; men, 55.4%) agreed come for an outpatient visit and to participate in the “COVID-19-follow-up” program. Since discharge, 8% (17) of patients required new hospitalizations, and more than a half of these patients (58.8%; 10/17) had CVD-related hospitalizations. A total of 8.4% (18) patients experienced worsening of hypertension, 9 (4.2%) patients had newly diagnosed hypertension, 2 (0.9%) – coronary artery disease patients experienced new/recurrent angina symptoms. 4 (1.9%) patients had newly diagnosed coronary artery disease, and one patient had an ischemic stroke. At the outpatient visit, 114 (53.5%) patients had some symptoms, most frequently, shortness of breath (33%), fatigue (27.4%), chest pain (11.3%), and abnormal heartbeats (8.5%). Based on the mMRC Scale, 59% of patients had dyspnea of varying severity. Most patients had a normal vital capacity (VC), which was moderately reduced in 3.3% and severely reduced in 0.5% of patients. Chest CT scans were obtained in 78 (36.6%) patients, whose worst lung damage scores during hospitalization were CT3 or CT4. One in ten patients (10.8%) with severe lung damage during acute infection had persisting ground glass opacities, 35.9% developed fibrotic changes, 79.6% of patients had linear or fine focal opacities. According to the 6MWT data, 12.3% of patients walked less than 70% of the predicted distance, 67% walked 71 to 99% of the predicted distance, and 20.7% of patients were able to walk 100% of their predicted distance.Conclusion. These data suggest long-term negative sequelae of COVID-19 in more than half of hospitalized patients

Эффективность и безопасность Бенакорта (раствор будесонида) при купировании обострения бронхиальной астмы

The study was designed to search efficiency and safety of the 3-rd generation glucocorticosteroid (GCS) budesonide (Benacort) as 0.05 % nebulized solution in patients with exacerbation of moderate bronchial asthma (BA). The study involved 18 males and 12 females aged 42 to 65 yrs suffering from BA for 3 months to 30 yrs, 27 of them completed the investigation. Three patients broke off the study because of unpleasant taste, sour throat, cough attacks during the inhalations. Before the study 22 patients had not received any basic therapy, 8 ones had been treated with inhaled GSC 600 to 1 200 meg daily or cromones. Starting the study all the patients had moderate exacerbations of BA.The budesonide solution was inhaled via a nebulizer 1 000 to 2 000 meg daily. All the patients also received inhaled β2-agonists. The efficacy of budesonide was evaluated with clinical picture, lung function parameters, need in β2-agonists. The therapy with nebulized budesonide lasted 7 to 10 days. The full control of BA was reached in 5 (18 % ) of the patients, sufficient control was in 10 (37 % ) and partial control was obtained in 13 (48 % ) of them. There were not significant shifts in endogenous cortisol and glucose levels, arterial blood pres­ sure and heart beat rate parameters for the treatment period. So, this study demonstrated that the nebulized Benacort is highly effective and safe when used in patients with BA exacerbations. Combined administration of nebulized β2-agonists and GCS is thought to be the alternative for systemic GCS and xanthines.Цель исследования: изучить эффективность и безопасность глюкокортикостероида (ГКС) III поколения будесонида (Бенакорт) в виде 0,05%-ного раствора для ингаляции с помощью небулайзера у больных с обострением бронхиальной астмы (БА) средней тяжести.В исследование вошли 18 мужчин и 12 женщин в возрасте от 42 до 65 лет с верифицированным диагнозом БА и давностью заболевания от 3 мес. до 30 лет, из них закончили исследование 27 человек, 3 отказались от продолжения лечения раствором будесонида из-за неприятного привкуса, першения в горле, пароксизмального кашля во время ингаляции. Базовая терапия у 22 больных отсутствовала, у 8 была представлена ингаляционными ГКС в дозе 600-1 200 мкг в сутки (в пересчете на беклометазона дипропионат) или кромонами. На начало исследования у больных диагностировано обострение средней тяжести. Раствор Будесонида вводился через небулайзер в дозе от 1 000 до 2 000 мкг в сутки. Кроме того, больные получали ингаляционные β2-агонисты. Эффективность будесонида оценивалась по клинической картине, показателям ФВД , потребности в β2-агонистах. Длительность терапии раствором будесонида через небулайзер составила от 7 до 10 дней. К 10-му дню лечения полный контроль над течением БА установлен у 5 (18 % ), хороший — у 10 (37 % ), неполный контроль — у 13 (48 % ) больных. На фоне лечения не было отмечено достоверных изменений в показателях эндогенного кортизола и глюкозы крови, негативных изменений АД и ЧСС.Таким образом, проведенное клиническое исследование показало, что препарат бенакорт, применяемый с помощью небулайзера, обладает высокой эффективностью и безопасностью у больных БА в стадии обострения. Сочетанное использование β2-агонистов и глюкокортикостероидов с помощью небулайзера может быть альтернативой системным ГКС и метилксантинам при купировании обострения БА

2020 Clinical practice guidelines for Myocarditis in adults

Russian Society of Cardiology (RSC)With the participation: Eurasian Association of Therapists (EUAT), Society of Specialists in Heart Failure (OSSN), Russian Scientific Medical Society of Therapists (RNMOT), Russian Society of Pathologists, Russian Society of Radiologists and Radiologists (RSR)Endorsed by: Research and Practical Council of the Ministry of Health of the Russian Federatio

ASSESSMENT OF CLINICO-ECONOMIC EFFICACY OF MEDICAL TREATMENT OF STABLE ISCHEMIC HEART DISEASE PATIENTS WHO UNDERWENT MYOCARDIAL REVASCULARIZATION

Background: Impractical use of pharmaceuticals is a serious problem of the Russian healthcare system. Implementation of pharmacoeconomic analysis into the logistic technologies of medical organizations may promote the solution of this problem.Aim: To analyze real-practice data on medical therapy of patients with stable ischemic heart disease (IHD) during their hospital stay for transcutaneous coronary stent placement and coronary artery bypass grafting.Materials and methods: With the help of a structured form on medical treatment we extracted and analyzed data from 131 clinical records of patients with stable IHD who were hospitalized in 2014 to the Department of Internal Diseases and Department of Cardiovascular Surgery; 60 were patients after stent placement and 71, after coronary artery bypass grafting. We performed an ABC/VEN analysis of their treatment. Groups of pharmaceuticals for VEN analysis were formed according to the Recommendations of Russian National Atherosclerosis Society on Diagnosis and treatment of chronic IHD (Recommendations of Russian National Atherosclerosis Society, 2013) based on European Society of Cardiology guidelines on the management of stable coronary artery disease (ESC guidelines, 2013). We assessed if the treatment administered corresponded to the current Standard of care to patients with stable IHD – SMP No 2.01.216.0 (Russian Federal Standard, 2007).Results: A mismatch between medical treatment that was performed in the Departments of Internal Diseases and of Cardiovascular Surgery, and that recommended by the Russian Federal Standard (2007), was found. The regimens used include the majority of agents recommended by the Russian National Atherosclerosis Society (2013) and the ESC guidelines (2013). In the Department of Internal Diseases, the mean cost of medical treatment during the whole period of stay in the hospital was 79.6 rubles. The group A agents (those with cumulative cost percentage = 80%) were represented by 9 items from the total of 54. There was a low percentage of medicines that were not indicated for this disease (13 agents, or 9.5% of the total medical costs), and all of them were administered for the treatment of concomitant disorders. In general, medical treatment performed in the Department of Internal Diseases corresponded to the ESC guidelines (2013). The costs of medical treatment during the whole period of stay in the Department of Cardiovascular Surgery was 10 741.9 rubles. The group A included 9 agents from the total of 78 used. Sixty eight per cent of costs were related to pharmaceuticals not having compelling indications (solutions, detoxification agents, agents for prevention of gastrointestinal adverse effects), whereas the costs of vitally important drugs were only 12.3% of the total and those of necessary drugs (including antibacterials), 19.7%.Conclusion: It is obviously necessary to update the current Russian Federal Standard (2007), with inclusion of data corresponding to the worldwide trends and guidelines of the Russian National Atherosclerosis Society (2013), at least for two patient groups: those after coronary stent placement and after coronary artery bypass grafting. The elaboration of criteria for administration of medical treatment and strict compliance with them in the real practice would allow for controlling of medical treatment costs, to prevent polypragmasia and adverse drug reactions