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

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

PSYCHOSOMATICS IN THE CONTEXT OF THE DEVELOPMENT OF INTEGRATIVE MEDICINE

Integrative medicine represents a promising modern approach to examination and treatment of large population of patients managed by the specialists in psychosomatics and somatopsychiatry. In Russia, experience of teamwork is scarce and non-common. However, implementation of this model of work is encouraged by accumulating evidence of existence of common mechanisms of the development of numerous somatic diseases and psychiatric disorders

CYTOKINE PROFILE OF Th1-, Th2- AND Th17-LYMPHOCYTE SUBPOPULATIONS IN INFECTIOUS MYOCARDITIS

Background: Type 17 T-helpers (Th17) were first identified more than 10 years ago. Though, there are only limited studies on the role of Th17- mediated mechanisms in the immune pathogenesis of acute myocarditis and dilative cardiomyopathy. Aim: To assess specific cytokine profile in patients with infectious immune myocarditis and post-myocarditis cardiosclerosis. Materials and methods: 35 patients with infectious immune myocarditis, 39 patients with post-myocarditis cardiosclerosis and 10 healthy volunteers (control group) were enrolled. 17 subjects with infectious immune myocarditis had manifest heart failure. Mean concentrations of Th1-, Th2- and Th17-derived cytokines were measured using solid-phase enzyme-linked immunosorbent assay panel manufactured by VectorBest ZAO (Russia). For statistical analysis, PASW Statistics software was used. Results: Compared to healthy controls, patients with infectious immune myocarditis had higher serum interferon-gamma (IF-γ) concentrations and more than 3-fold increase of serum interleukin (IL)-4. They also had almost 7-fold increase of IL-17A and Th17 effector cytokines – IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients with infectious immune myocarditis and moderate or no symptoms of heart failure had significantly lower concentrations of IF-γ compared to patients with advanced heart failure. Cytokine concentrations peaked during the first 2 week of the disease, with following decrease. On the contrary, serum IL-4 grew significantly by the end of the first month and during the second month of the disease. Raised concentrations of IL-17A, IL-8 and GM-CSF were found throughout the period from the second week to the second month of the disease. Th17-derived cytokines concentrations were significantly increased in patients with post-myocarditis cardiosclerosis. Compared to the controls, IL-17A almost doubled, IL-8 increased by 51%, and GM-CSF – by 50%. Elevated concentrations of IL-4, IL-17A, IL-8 and GM-CSF were found in patients with duration of post-myocarditis cardiosclerosis less than 6 months. Conclusion: Disorders of anti-infective immunity and deficient self-limitation mechanisms of immune response play an important role in the development and progression of inflammatory myocardial diseases

IMMUNOLOGICAL FEATURES OF INFLAMMATORY MYOCARDIAL DISEASES DUE TO VIRAL INFECTIONS

Background: Autoantibodies to myocardial antigenic epitopes and corresponding autoreactive T cell clones play an important role in myocardial damage and in pathogenesis of infectious immune myocarditis. T lymphocytes subpopulations/regulatory T cells balance as well as T cell-derived cytokines are crucial in the mechanisms of immune regulation in myocarditis. Aim: To assess quantitative parameters and functional characteristics of basic peripheral blood lymphocytes subpopulations in patients with infectious immune myocarditis and post-myocarditis cardiosclerosis. Material and methods: 35 patients with infectious immune myocarditis and 39 patients with post-myocarditis cardiosclerosis were included. Among infectious immune myocarditis patients, 17 patients had advanced congestive heart failure (CHF) (NYHA III), and 18 patients had mild, moderate or no heart failure (NYHA 0-II). Among cardiosclerosis patients, 18 patients had no CHF, and 21 had only mild symptoms of heart failure (NYHA I). 10 healthy volunteers were enrolled in the control group. Populations and subpopulations of peripheral blood lymphocytes and markers of lymphocytes activation were studied using quadricolor laser flow cytometry (FACSCalibur) and suitable monoclonal antibodies (Becton Dickinson, USA). Results: Inflammatory myocardial diseases are characterized by alterations of innate and adaptive immunity. In our study, patients with infectious immune myocarditis and post-myocarditis cardiosclerosis had significantly reduced numbers of natural killer T cells irrespective of CHF symptoms and disease duration. T cell immunity disturbances were characterized by decreased numbers of CD3+CD4+ cells depending from the disease duration and symptoms severity. Patients with infectious immune myocarditis also had increased numbers of B cells. Immune activation was demonstrated both in infectious immune myocarditis and (less prominent) in post-myocarditis cardiosclerosis. Increased expression of early activation marker CD25 was found during the first 2 weeks from the disease onset in patients with infectious immune myocarditis. In 1 month and during the second month of the disease, increased numbers of T cells and non-T lymphocytes were demonstrated along with late activation manifested by the expression of HLA-DR antigen. Different severity of CHF symptoms was associated with different patterns of activation markers. Increased expression of apoptosis marker CD95 was found in both infectious immune myocarditis and post-myocarditis cardiosclerosis; maximal CD95 values were demonstrated in myocarditis patients in 1 month after the disease onset. Conclusion: Disturbances of anti-infection immunity and self-limitation mechanisms of immune reactions play an important role in the development and progression of inflammatory myocardial diseases