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.

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.

Background. A few cases of combination of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) with left ventricular noncompaction (LVNC) have been described. Aims to study the genetics, diagnostical features and clinical course of the combination of ARVC with LVNC. Methods. 58 patients with ARVC diagnosis (26 men; mean age 39.1 14.2 years; mean follow-up period 21.5 [6; 60] months) and 125 patients with LVNC (74 men; mean age 46.4 15.1 years; mean follow-up period 14 [3; 40] months). All patients underwent electrocardiogram (ECG), echocardiography, 24-h ECG monitoring. Heart MRI was performed in 53 (91.4%) patients with ARVC and 60 (48%) with LVNC, heart CT in 18 (31%) patients with ARVC and 89 (71.2%) with LVNC. For all patients with combination of ARVC and LVNC DNA-diagnostic was performed using both ARVC (PKP2, DSG2, DSP, DSC2, JUP, TMEM43, TGFB3, PLN, LMNA, DES, CTTNA3, EMD, SCN5A, LDB3, CRYAB, FLNC) and LVNC (MYH7, MYBPC3, TAZ, TPM1, LDB3, MYL2, MYL3, ACTC1, TNNT2, TNI3) gene panels. Results. Combination of ARVC and LVNC was found in 9 patients (15.5% of patients form ARVC cohort and 7.2% from LVNC cohort). These patients were distinguished from patients with isolated ARVC or LVNC by aggressive ventricular arrhythmias (frequent premature ventricular beats, sustained ventricular tachycardia, significantly worse antiarrhythmic therapy effect, appropriate shocks of implanted cardioverter-defibrillators (ICD) in all patients with ICD). Patients with combination of ARVC + LVNC were also distinguished from patients with isolated LVNC by the dilatation of RV, low QRS voltage on ECG, presence of AV block, absence of signs of LV hypertrophy on ECG. LV dilatation with reduction of its ejection fraction distinguished patients with mixed cardiomyopathy from patients with isolated ARVC. Potentially pathogenic variants (IVV classes of pathogenicity) and variants of unclear clinical significance (III class of pathogenicity) were found in both desmosomal and non-desmosomal genes in 78% of patients, including 3 (33%) in DSP gene. Conclusions. The combination of ARVC and LVNC can be caused by mutations in both desmosomal and non-desmosomal genes and has typical features: aggressive, resistant ventricular rhythm abnormalities leading to appropriate ICD shocks and a high risk of sudden cardiac death.

Introduction: Commonly accepted clinical classification of arrhythmogenic right ventricular cardiomyopathy (ARVC) is still not developed. Objective: To study the clinical forms of ARVC. Methods: Fifty-four patients (38.7 ± 14.1 years, 42.6% men) with ARVC. Follow-up period: 21 (6–60) months. All patients underwent electrocardiography, 24 h-Holter monitoring, echocardiography, and DNA diagnostic. Magnetic resonance imaging was performed in 49 patients. Results: According to the features of clinical course of ARVC, 4 clinical forms were identified. (I) Latent arrhythmic form (n = 27) – frequent premature ventricular contractions and/or nonsustained ventricular tachycardia (VT) in the absence of sustained VT and syncope; characterized by absence of fatal arrhythmic events. (II) Manifested arrhythmic form (n = 11) – sustained VT/ventricular fibrillation; the high incidence of appropriate implantation of cardioverter-defibrillator (ICD) interventions (75%) registered. (III) ARVC with progressive chronic heart failure (CHF, n = 8) as the main manifestation of the disease; incidence of appropriate ICD interventions was 50%, mortality rate due to CHF was 25%. (IV) Combination of ARVC with left ventricular noncompaction (n = 8); characterized by mutations in desmosomal or sarcomere genes, aggressive ventricular arrhythmias, appropriate ICD interventions in 100% patients. Described 4 clinical forms are stable in time, do not transform into each other, and they are genetically determined. Conclusions: The described clinical forms of ARVC are determined by a combination of genetic and environmental factors and do not transform into each other. The proposed classification could be used in clinical practice to determine the range of diagnostic and therapeutic measures and to assess the prognosis of the disease in a particular patient.

The possibility of heart inflammation (both myocardial and endocardial) months after a coronavirus disease 2019 (COVID-19) has not been practically studied, especially since approaches to the treatment of myocarditis in combination with various endocarditis forms have not been developed.Aim. To study the prevalence and mechanisms of SARS-CoV-2-associated endocardial injury in patients with morphologically verified post-COVID-19 myocarditis, as well as to develop approaches to comprehensive therapy.Material and methods. The study included 18 patients with severe morphologically verified post-COVID-19 myocarditis (men, 9; 51,1±9,4 years; 35 to 66 years). Patients with prior verified myocarditis/myocardial infarction, rheumatic heart disease, and systemic immune diseases were excluded. The average time after COVID-19 was 6,5 [3.5; 10] months The diagnosis of myocarditis was confirmed by endomyocardial biopsy (including immunohistochemical examination with antibodies to CD3, CD20, CD45, CD68, and to SARS-CoV-2 antigens; polymerase chain reaction for SARS-CoV-2 RNA, DNA of cardiotropic viruses). The blood level of anticardiac antibodies was determined by indirect immunofluorescence. In addition, echocardiography, magnetic resonance imaging (n=8), cardiac multislice tomography (n=1), and coronary angiography (n=14) were performed.Results. Biopsy revealed active (n=12) and borderline (n=3) lymphocytic myocarditis, eosinophilic (n=2) and giant cell (n=1) myocarditis. In 4 patients, nonbacterial thrombotic endocarditis (NBTE) with parietal and intravascular thrombosis was diagnosed, and in one patient — infective endocarditis (IE) of the bicuspid aortic valve. Myocardial persistence of SARS-CoV-2 was detected in 72% of cases (in 3 patients — with NBTE; in 1 — with IE; in 9 — without endocarditis). Titers of anticardiac antibodies increased by 3-4 times in 94% of patients. Patients with endocarditis were characterized by larger heart chambers, lower ejection fraction (27,5±6,6 vs 36,0±13,4%), more severe pulmonary hypertension, and valvular regurgitation. Intraventricular thrombosis according to echocardiography/magnetic resonance imaging and cardiac embolism was not observed. Treatment in all patients included methylprednisolone at an average dose of 24 mg a day. In 10 patients, the result was monitored for at least 3 months as follows: the ejection fraction was 46,0±12,7% and 44,3±7,3% in patients with and without endocarditis, respectively.Conclusion. Endocarditis in patients with post-COVID-19 myocarditis was detected in 28% (1 patient — IE; 4 — NBTE). The key mechanisms of post-COVID-19 myocarditis and NBTE are long-term (up to 18 months) myocardial persistence of SARS-Cov-2 and the development of an autoimmune reaction. Endocarditis was diagnosed in more severe patients, including those with giant cell and eosinophilic myocarditis. The effectiveness of steroid therapy in combination with anticoagulants in patients with NBTE requires further study. In case of IE, steroids can also be used in the treatment of myocarditis (in combination with antibiotics and immunoglobulin).

Background: Myocardial disease is an important component of the wide field of cardiovascular disease. However, the phenomenon of multiple myocardial diseases in a single patient remains understudied. Aim: To investigate the prevalence and impact of myocarditis in patients with genetic cardiomyopathies and to evaluate the outcomes of myocarditis treatment in the context of cardiomyopathies. Methods: A total of 342 patients with primary cardiomyopathies were enrolled. The study cohort included 125 patients with left ventricular non-compaction (LVNC), 100 with primary myocardial hypertrophy syndrome, 70 with arrhythmogenic right ventricular cardiomyopathy (ARVC), 60 with dilated cardiomyopathy (DCM), and 30 with restrictive cardiomyopathy (RCM). The diagnosis of myocarditis was based on data from myocardial morphological examination or a non-invasive diagnostic algorithm consisting of an analysis of clinical presentation, anti-cardiac antibody (Ab) titres, and cardiac MRI. Results: The prevalence of myocarditis was 74.3% in ARVC, 56.7% in DCM, 54.4% in LVNC, 37.5% in RCM, and 30.9% in HCM. Myocarditis had a primary viral or secondary autoimmune nature and manifested with the onset or worsening of chronic heart failure (CHF) and arrhythmias. Treatment of myocarditis in cardiomyopathies has been shown to stabilise or improve patient condition and reduce the risk of adverse outcomes. Conclusions: In cardiomyopathies, the genetic basis and inflammation are components of a single continuum, which forms a complex phenotype. In genetic cardiomyopathies, myocarditis should be actively diagnosed and treated as it is an important therapeutic target.