Purpose To study clinical features of myocarditis and its possible mechanisms (including persistence of SARS-Cov-2 in the myocardium) in the long-term period after acute COVID-19. Methods Fifteen patients (8 male and 7 female, mean age 47.8±13.4, 24–65 years) diagnosed with postcovid myocarditis were included in the study. The diagnosis of COVID-19 was confirmed by positive PCR results in 40%, and seroconversion in all patients. The average time of admission after COVID-19 was 4 [3; 7] months, from 2 to 9 months. The diagnosis of myocarditis was confirmed by cardiac MRI in 10 patients and by right ventricular endomyocardial biopsy (EMB) in 6 patients. The PCR for cardiotropic viruses and PCR with immunohistochemical study for SARS-Cov2 detection were used. All patients had study for anti-heart antibodies (AHA), EchoCG, and Holter ECG. Coronary atherosclerosis was excluded in all patients over 40 years (7 coronary angiography, 4 cardiac CT). Results A clear association of the cardiac symptoms with a previous new coronavirus infection was noted in all patients. The symptoms started 1–5 months following COVID-19. MRI showed subepicardial and intramyocardial LGE, signs of hyperemia, increased T1 relaxation time, edema. AHA levels were increased 3–4-fold in 73%. Two variants of postcovid myocarditis were observed. 1. Arrhythmic variant (n=6) – newly developed frequent supraventricular or ventricular extrasystole, recurrent atrial fibrillation in the absence of systolic dysfunction. 2. Decompensated variant with biventricular heart failure (n=9): the mean LV EF was 34.1±7.8% (23 to 46%), LV EDD 5.8±0.7 cm, EDV 153.8±46.1 ml, pulmonary artery systolic pressure 40.7±11.2 mmHg. In one case, myocarditis was accompanied by IgG4- and ANCA-negative aortitis. SARS-Cov-2 RNA was detected in 4 of 5 myocardial biopsies (in one case the material in the study). The longest period of virus persistence after COVID-19 was 9 months. By using spike and nucleocapsid antibodies, coronavirus was detected in cardiomycytes and macrophages. Data of patients with morphologically proved myocarditis are presented in Table 1. Lymphocytic myocarditis was diagnosed and confirmed immunohistochemically (n=5); giant cell myocarditis with atrial standstill was detected in one more case (Fig. 1). Three patients had also signs of endocarditis, in two cases with parietal thrombosis. Conclusions COVID-19 can lead to the subacute and chronic myocarditis of varying severity. Post-COVID myocarditis manifests itself in two main clinical forms - isolated arrhythmias and systolic dysfunction with heart failure. Post-COVID myocarditis is characterized by prolonged persistence of coronavirus (up to 9 months in this study, in most patients with decompensated variant) in combination with high immune activity (high titers of AHA), which should be considered as the main mechanisms of its long-term course. Treatment approaches for such myocarditis require investigation. FUNDunding Acknowledgement Type of funding sources: None. Table 1. Patients with EMB proved myocarditis Figure 1. The EMB in postcovide myocarditis

Aim    To study clinical features of myoendocarditis and its possible mechanisms, including persistence of SARS-Cov-2 in the myocardium, in the long-term period following COVID-19.Material and methods    This cohort, prospective study included 15 patients aged 47.8±13.4 years (8 men) with post-COVID myocarditis. The COVID-19 diagnosis was confirmed for all patients. Median time to seeking medical care after COVID-19 was 4 [3; 7] months. The diagnosis of myocarditis was confirmed by magnetic resonance imaging (MRI) of the heart (n=10) and by endomyocardial biopsy of the right ventricle (n=6). The virus was detected in the myocardium with PCR; immunohistochemical (IHC) study with antibody to SARS-Cov-2 was performed; anticardiac antibody level was measured; and echocardiography and Holter monitoring were performed. Hemodynamically significant coronary atherosclerosis was excluded for all patients older than 40 years.Results    All patients showed a clear connection between the emergence or exacerbation of cardiac symptoms and COVID-19. 11 patients did not have any signs of heart disease before COVID-19; 4 patients had previously had moderate arrhythmia or heart failure (HF) without myocarditis. Symptoms of myocarditis emerged at 1–5 months following COVID-19. MRI revealed typical late gadolinium accumulation, signs of hyperemia, and one case of edema. The level of anticardiac antibodies was increased 3-4 times in 73 % больных. Two major clinical variants of post-COVID myocarditis were observed. 1. Arrhythmic (n=6), with newly developed extrasystole or atrial fibrillation without systolic dysfunction. 2. Decompensated variant with systolic dysfunction and biventricular HF (n=9). Mean left ventricular ejection fraction was 34.1±7.8 %, and left ventricular end-diastolic dimension was 5.8±0.7 cm. In one case, myocarditis was associated with signs of IgG4‑negative aortitis. SARS-Cov-2 RNA was found in 5 of 6 biopsy samples of the myocardium. The longest duration of SARS-Cov-2 persistence in the myocardium was 9 months following COVID-19. By using antibody to the Spike antigen and nucleocapsid, SARS-Cov-2 was detected in cardiomyocytes, endothelium, and macrophages. Five patients were diagnosed with lymphocytic myocarditis; one with giant-cell myocarditis; three patients had signs of endocarditis (infectious, lymphocytic with mural thrombosis).Conclusion    Subacute/chronic post-COVID myocarditis with isolated arrhythmias or systolic dysfunction is characterized by long-term (up to 9 months) persistence of SARS-Cov-2 in the myocardium in combination with a high immune activity. Endocarditis can manifest either as infectious or as nonbacterial thromboendocarditis. A possibility of using corticosteroids and anticoagulants in the treatment of post-COVID myoendocarditis should be studied.

Purpose To study the clinical signs and mechanisms (viral and autoimmune) of myoendocarditis in the long‐term period after COronaVIrus Disease 2019 (COVID‐19). Methods Fourteen patients (nine male, 50.1 ± 10.2 y.o.) with biopsy proven post‐COVID myocarditis were observed. The diagnosis of COVID‐19 was confirmed by IgG seroconversion. The average time of admission after COVID‐19 was 5.5 [2; 10] months. An endomyocardial biopsy (EMB) of the right ventricle was obtained. The biopsy analysis included polymerase chain reaction diagnosis of viral infection, morphological, immunohistochemical (IHC) examination with antibodies to CD3, CD45, CD68, CD20, SARS‐Cov‐2 spike, and nucleocapsid antigens. Coronary atherosclerosis was ruled out in all patients over 40 years. Results The new cardiac symptoms (congestive heart failure 3–4 New York Heart Association class with severe right ventricular involvement, various rhythm, and conduction disturbances) appeared 1–5 months following COVID‐19. Magnetic resonance imaging showed disseminated or focal subepicardial and intramyocardial late gadolinium enhancement, hyperemia, edema, and increased myocardial native T1 relaxation time. Antiheart antibodies levels were increased 3–4 times in 92.9% of patients. The mean left ventricular (LV) ejection fraction (EF) was 28% (24.5; 37.8). Active lymphocytic myocarditis was diagnosed in 12 patients, eosinophilic myocarditis in two patients. SARS‐Cov‐2 RNA was detected in 12 cases (85.7%), in association with parvovirus B19 DNA—in one. Three patients had also endocarditis (infective and nonbacterial, with parietal thrombosis). As a result of steroid and chronic heart failure therapy, the EF increased to 47% (37.5; 52.5). Conclusions COVID‐19 can lead to long‐term severe post‐COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post‐COVID myoendocarditis.

A 60-year-old male with hypertrophic cardiomyopathy, conduction disorders, post-COVID-19 myopericarditis and heart failure was admitted to the hospital’s cardiology department. Blood tests revealed an increase in CPK activity, troponin T elevation and high titers of anticardiac antibodies. Whole exome sequencing showed the presence of the pathogenic variant NM_213599:c.2272C>T of the ANO5 gene. Results of the skeletal muscle biopsy excluded the diagnosis of systemic amyloidosis. Microscopy of the muscle fragment demonstrated sclerosis of the perimysium, moderate lymphoid infiltration, sclerosis of the microvessels, dystrophic changes and a lack of cross striations in the muscle fibers. Hypertrophy of the LV with a low contractile ability, atrial fibrillation, weakness of the distal skeletal muscles and increased plasma CPK activity and the results of the skeletal muscle biopsy suggested a diagnosis of a late form of distal myopathy (Miyoshi-like distal myopathy, MMD3). Post-COVID-19 myopericarditis, for which genetically modified myocardium could serve as a favorable background, caused heart failure decompensation.

Кафедра факультетской терапии №1 Московской медицинской академии им. И.М. Сеченова Цель. Оценить частоту резистентности к ацетилсалициловой кислоте (АСК) и клопидогрелю у больных острым коронарным синдромом (ОКС) с подъемом сегмента ST и выявить возможные клинические факторы, способствующие развитию данного состояния. Материал и методы. В исследование включены 58 больных (49 мужчин, 9 женщин) в возрасте от 37 до 84 лет (в среднем 60,8±12,3 лет) с острым коронарным синдром с подъемом сегмента ST. Агрегацию тромбоцитов исследовали методом Борна. Критерием резистентности к АСК являлся уровень агрегации ≥20% после индукции арахидоновой кислотой. При снижении АДФ-индуцированной агрегации тромбоцитов <10%, 10-29%, и ≥30% относительно исходного уровня пациентов рассматривали как резистентных, «частично резистентных» и чувствительных к терапии клопидогрелем, соответственно. Результаты. АСК и клопидогрель вызывали значимое снижение агрегации, индуцированной арахидоновой кислотой и АДФ, к 7 дню лечения (р<0,05). Наиболее высокая частота резистентности выявлена у больных сахарным диабетом (71,1% к АСК и 57,1% к клопидогрелю) и ожирением (42,9% к клопидогрелю). Заключение. Среди больных ОКС с подъемом сегмента ST частота резистентности достигает 28,9% к АСК и 24,4% к клопидогрелю. У больных сахарным диабетом, ожирением частота резистентности достоверно выше (р<0,05). У резистентных к АСК и клопидогрелю больных достоверно выше частота ранних осложнений инфаркта миокарда. Ключевые слова: резистентность к ацетилсалициловой кислоте, резистентность к клопидогрелю, острый коронарный синдром, агрегация тромбоцитов. РФК 2008;2:23-29 Antiplatelet therapy resistance in patients with acute coronary syndrome with ST-segment elevation D.H. Ainetdinova, A.Е. Udovichenko, V.A. Sulimov Department of faculty therapy №1, Moscow Medical Academy named after I.M. Setchenov Aim. To evaluate the incidence of acetylsalicylic acid (ASA) and clopidogrel resistance in patients with acute coronary syndrome with ST-segment elevation and to find out possible clinical factors, contributing to this state. Material and methods. 58 patients with acute coronary syndrome with ST-segment elevation (49 men, 9 women) were included into the study. Age of patients ranged from 37 tо 84 y.o. (60,8±12,3 y.o. in average). Platelet aggregation was assessed by the Born's method. Level of arachidonic acidinduced aggregation ≥20% considered as ASA resistance. Decreasing of ADP-induced platelet aggregation <10%, 10-29%, and ≥30% compared to the basal level considered as clopidogrel resistance, "partial clopidogrel resistance" or clopidogrel sensitiveness, respectively. Results. ASA and clopidogrel decreased arachidonic acid-induced and ADP-induced aggregation after 7 days of the therapy compared to the basal levels (р<0,05). The highest incidence of resistance was registered in patients with diabetes mellitus (71,1% to ASA, 57,1% to clopidogrel) and obesity (42,9% to clopidogrel). Conclusion. The incidence of ASA and clopidogrel resistance reached to 28,9% and 24,4% respect...