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.

Giant cell myocarditis (GCM) is a rare condition. Its association with SARS‐CoV‐2 has not been described before. The 46‐year‐old female patient was admitted to the clinic on September 2020. She had 7 year adrenal insufficiency history and infarct‐like debut of myocardial disease in November 2019. After COVID‐19 in April 2020, cardiac disease progressed. The examination showed low QRS voltage, QS complexes in V 1 –V 5 leads, atrial standstill, left ventricular systolic and restrictive dysfunction, elevated anti‐heart antibodies, and subepicardial late gadolinium enhancement by magnetic resonance imaging. Endomyocardial biopsy and pacemaker implantation were performed, but the patient died suddenly due to ventricular tachycardia or ventricular fibrillation (the resuscitation was ineffective). The autopsy revealed GCM, SARS‐CoV‐2, and Parvovirus B19 were detected in the myocardium. The role of SARS‐CoV‐2 in the pathogenesis of autoimmune myocarditis is discussed.

The same variants in sarcomeric genes can lead to different cardiomyopathies within the same family. This gave rise to the concept of a continuum of sarcomeric cardiomyopathies. However, the manifestations and evolution of these cardiomyopathies in pathogenic variant carriers, including members of the same family, remains poorly understood. We present a case of familial sarcomeric cardiomyopathy caused by heterozygous truncating pathogenic variant p.Q1233* in cardiac myosin-binding protein C (MyBPC3) gene. The proband was first diagnosed with restrictive cardiomyopathy combined with left ventricular noncompaction (LVNC) and sarcoidosis at the age of 64. The predominantly restrictive phenotype of cardiomyopathy is considered to be a result of interaction between LVNC and sarcoid myocarditis. His 39-year-old son and 35-year-old daughter have identical non-obstructive asymmetric hypertrophic cardiomyopathy. The risk of sudden cardiac death in the son is high due to myocardial fibrosis, ischemia and nonsustained VT. We assume that both phenotypes in the family may have originally been different or there may have been a gradual transformation of the hypertrophic phenotype into LVNC. Myocarditis is regarded as an important epigenomic modifier of sarcomeric cardiomyopathy. In the proband and his son, cardioverter-defibrillators were implanted, and the proband experienced appropriate shocks due to ventricular tachycardia/fibrillation. The proband was also treated with corticosteroids. His death at the age of 69 years occurred due to acute gastric hemorrhage accompanied by progressive heart failure. This report confirms the concept of the phenotypic continuum of sarcomeric cardiomyopathies and describes possible phenotypic patterns and their transformation over time.

Цель. Выделить устойчивые клинические формы аритмогенной дисплазии правого желудочка (АДПЖ) с учетом различного вклада генетических и воспалительных механизмов, проанализировать особенности дифференциальной диагностики и лечения при каждом из вариантов болезни. Материал и методы. Основную группу составили 50 пациентов с достоверным (n=26), вероятным (n=13) или возможным (n=11) диагнозом АДПЖ, средний возраст 38,1±14,6 лет, мужчины -20 (40%), срок наблюдения 13,5 [4; 34] мес. Группу сравнения составили 58 пациентов, имеющих отдельные критерии диагноза АДПЖ, недостаточные для постановки диагноза. Всем пациентам выполнены ЭКГ, суточное мониторирование ЭКГ по Холтеру, ЭхоКГ, дополнительно в основной группе -ДНК-диагностика (n=46), МРТ сердца (n=44), ЭКГ высокого разрешения (n=16), эндомиокардиальная биопсия ПЖ (ЭМБ, n=2), аутопсия (n=2). В группе сравнения МРТ выполнена 32 больным, ЭМБ (n=7), аутопсия (n=1). Результаты. На основании анализа клинических данных и характера течения заболевания выделены 4 стабильных во времени клинических формы АДПЖ, которые не склонны к взаимному переходу: латентная аритмическая (50% больных), развернутая аритмическая (20%), АДПЖ с преобладанием бивентрикулярной хронической сердечной недостаточности (ХСН, 16%) и АДПЖ в сочетании с некомпактным миокардом (НКМ) левого желудочка (14%). Развитие той или иной формы определяется как генетическими факторами, так и присоединением миокардита (в % соответственно для каждой формы). В диагностике латентной аритмической формы (частая правожелудочковая экстрасистолия, ЖЭ, и/или неустойчивая правожелудочковая тахикардия, ЖТ) основное значение имели женский пол, синкопе в анамнезе (16%), внезапная смерть в семье (12%), ЭКГ-критерии и положительные результаты ДНК-диагностики (24%), развернутой аритмической формы (устойчивая ЖТ, УЖТ)внезапная смерть в семье (у 20%), МРТ-критерии (увеличение ПЖ со снижением его ФВ), ЭКГ-критерии и положительные результаты ДНК-диагностики (50%), АДПЖ с прогрессирующей ХСН -наличие устойчивой ЖТ (50%), синкопе (37,5%), преобладание недостаточности ПЖ с резким снижением его ФВ (25,7±15,0%), большие МРТ-и ЭКГ-критерии, снижение вольтажа QRS и положительные результаты ДНК-диагностики (38%). Сочетание АДПЖ и НКМ отличают частая ЖЭ, агрессивная ЖТ (57,1%), синкопе (42,9%) и ХСН с достоверно меньшей, чем при ДКМП, ФВ ПЖ. Летальность при I-IV формах составила соответственно 0%, 10%, 25% и 14,3%, оправданные срабатывания зарегистрированы у 8 из 13 (61,5%) больных с ИКД. Заключение. Целесообразно использование предложенной классификации АДПЖ в клинической практике с целью определения спектра диагностиче-ских и лечебных мероприятий и оценки прогноза заболевания у конкретного больного.Российский кардиологический журнал 2018, 2 (154): 19-31 http://dx.