Noncompact Myocardium with Dilated Phenotype: Manifestations, Treatment and Outcomes in Comparison with Other Forms of Dilated Cardiomyopathy Syndrome

Aim. To study the place of NCM in the structure of DCM, its clinical features and influence on prognosis in comparison with other forms of DCM syndrome.Methods. The NCM registry includes 125 patients, mean age 46.4±15.1 years, 74 men and 51 women, median follow-up 14 [4.0; 41.0] months. The DCM registry included 365 patients, mean age 46.4±15.1 years, 253 men and 112 women, median follow-up 14 [5; 43.75] months. The examination included electrocardiography (ECG), ECG Holter monitoring, echocardiography, blood anti-heart antibody level evaluation, and additionally cardiac computed tomography, magnetic resonance imaging, DNA diagnostics (in the MYH7, MYBPC3, TPM1, TNNI3, TNNT2, ACTC1, TAZ, ZASP (LDB3), MYL2, MYL3, DES, LMNA, EMD, TTR gene panel), coronary angiography, right ventricular endomyocardial biopsy.Results. The proportion of patients with DCM phenotype in the NCM registry was 40% (n=49), another 11% (n=15) had NCM diagnosed simultaneously with acute/subacute myocarditis. Lethality in these subgroups was 12.2% and 33.3%, respectively, and was significantly higher than in asymptomatic, ischemic and arrhythmic variants of NCM. In the DCM registry, the proportion of patients with NСM was 21% (n=78), and increased left ventricular (LV) trabecularity was detected in another 18% (n=64). DCM patients with and without NСM did not differ by baseline echocardiographic parameters, heart failure class, and cardiotropic therapy. Pathogenic mutations were detected in 14% of DCM patients with NCM and only 3% of other patients with DCM (p<0.001). Only in patients without NCM the presence of mutations had a significant effect on lethality. The patients with NCM compared with the others DCM patients showed significantly lower increase in EF in early and late period (from 31.0±10.2 to 34.8±11.0 and 37.1±10.9% [р<0.05] vs from 31.8±9.7 to 38.8±11.3 and 42.3±12.4% [р<0.01] respectively), a greater incidence of premature ventricular   beats (1568 [105;7000] vs 543.5 [77.75; 3194], p<0.05), appropriate defibrillator shocks and sudden deaths (17.9 vs 5.9%, p<0.001), intracardiac thrombosis (21.8 vs 13.5%, p=0.069) despite a greater frequency of anticoagulants (73.1 vs 57.4%, p<0<05). There were no significant differences in death (19.2 vs 18.5%) and transplantation (7.7 vs 3.8%) between patients with and without NCM. There were no cases of NCM regression.Conclusion. NCM is an independent form of DCM syndrome, which is characterized by higher frequency of pathogenic mutations, arrhythmic events, worse response to cardiotropic therapy, higher frequency of intracardiac thrombosis. The absence of mortality differences can be explained by the higher frequency of preventive interventions in this category of patients with DCM (prescription of anticoagulants, defibrillator implantation, heart transplantation)

Anticardiac antibodies in patients with severe and moderate COVID-19 (correlations with the clinical performance and prognosis)

The level and significance of anticardiac antibodies (ACA) in patients with COVID-19 infection have not yet been studied.Aim. To assess the level of various ACA in patients with severe and moderate COVID-19 infection and to identify the correlation of antibody profile with the clinical performance and prognosis.Material and methods. The study included 86 (38 women and 48 men) patients aged 20-90 years (60,2±16,6 years) who were hospitalized for moderate and severe COVID-19 infection in April-June 2020. Nasopharyngeal swab confirmed the disease in 59,3% of patients. In addition to the standard examination, electrocardiography and chest scan, level of antinuclear antibodies (ANA), antiendothelial cell antibodies (AECA), anti-cardiomyocyte antibodies, antibodies to anti-smooth muscles (ASMA) and cardiac conduction system fibers. Echocardiography was performed in 17 patients. Mean length of stay was 14 [12; 18] days. Death was considered as the primary endpoint.Results. Prevalence of heart disease and symptoms (including hypertension and coronary artery disease) was 45,3%. The manifestations of coronavirus heart damage include arrhythmias (supraventricular premature beats, 3,6%; atrial fibrillation, 9,3%), heart failure (9,3%), low QRS voltage (11,4%), repolarization abnormalities (41,9%), pericardial effusion (30%). An increase in troponin levels was observed in low number of patients. All types of cardiovascular disease correlated with the maximum D-dimer level (AUC, 0,752, p<0,01). Titers of two or more types of ACA were increased by 3 or more times in 25 (73,5%) patients. Significant (p<0,05) correlations of ANA level with cardiovascular symptoms/diseases in general (r=0,459), anti-cardiomyocyte antibodies — with the prevalence of pneumonia (r=0,472), shortness of breath severity (r=0,370), respiratory failure (r=0,387), oxygen therapy (r=0,388) and mechanical ventilation (r=0,469), as well as the presence of chest pain (r=0,374), QRS voltage decrease (r=0,415), maximum level of CRP (r=0,360) and LDH (r=0,360). ANA and anti-cardiomyocyte antibody levels strongly correlated with pericardial effusion (r=0,721 and r=0,745, respectively, p<0,05). The mortality rate was 9,3%. Heart failure was one of the death causes in 37,5%. The level of anti-cardiomyocyte antibodies and ASMA correlated with mortality (r=0,363, and r=0,426, p<0,05) and had a predictive value. Mortality in patients with cardiovascular disease was 17,9%, without — 2,2% (p<0,05). The most powerful predictive model for COVID-19 adverse outcomes includes age, diabetes, oxygen therapy extent, maximum leukocyte, C-reactive protein and D-dimer levels. However, a model that includes only age, diabetes, and cardiovascular disease also has sufficient predictive power (correlation coefficient, 0,568, p<0,001).Conclusion. An increase in ACA titers was detected in 73,5% of patients, correlated with mortality, in most cases reflects the general activity and severity of the disease and can be regarded as part of response in COVID-19. At the same time, a direct correlation with signs of myocardial damage, the presence and volume of pericardial effusion confirms the direct role of ACA in the development of myopericarditis

COVID-19 Pneumonia in Patients with Chronic Myocarditis (Recurrent Infectious Immune): Specifics of the Diseases Course, the Role of Basic Therapy (Part 1)

Patients with chronic myocarditis have a high risk of an unfavorable course of the novel coronavirus disease (COVID-19) due to the ability of the SARS-Cov-2 virus to independently cause acute myocarditis, to have a direct and cytokine-mediated cytopathic effect on the myocardium, as well as immunosuppressive therapy. At the same time, the features of the interaction of chronic myocarditis and COVID-19 have not been studied. The article describes a 31-year-old patient with a 10-year history of chronic recurrent infectious-immune myocarditis, who was on long-term immunosuppressive therapy (methylprednisolone and azathioprine in the past, then hydroxychloroquine). In May 2020, a serologically confirmed COVID-19 diagnosis was made. There were risk factors for the unfavorable course of coronavirus infection: heart failure and a history of persistent atrial fibrillation, male sex. Basic therapy with hydroxychloroquine (with an increase in its dose to 800-400 mg/day), ceftriaxone, and levofloxacin was carried out. The severity of pneumonia was moderate, despite febrile fever and severe intoxication. No relapses of arrhythmias, respiratory or heart failure were observed. Minimal laboratory (some increase in anticardial antibody titers) and echocardiographic signs of exacerbation of myocarditis without an increase in troponin T levels were revealed, which quickly regressed. It can be assumed that the maintenance immunosuppressive therapy of myocarditis with hydroxychloroquine had a positive effect on the course of coronavirus pneumonia and made it possible to avoid recurrence of myocarditis. Further study of the features of the course of the pre-existing myocarditis and pneumonia in COVID-19 is necessary

Register of adult patients with noncompact left ventricular myocardium: classification of clinical forms and a prospective assessment of progression

Aim. To study clinical forms of noncompact myocardium (NCM) in adults, the features of their manifestation, course and progression.Material and methods. The study included 116 adult patients with NCM of the left ventricle (LV) (67 men, mean age 46,3±15,1 years) and 42 patients with increased LV trabecularity (24 men, mean age 43,5±15,2 years). The mean LV end-diastolic diameter was 6,0±0,8 and 5,9±1,1 cm, LV ejection fraction was 38,6±14,0% and 44,6±18,3%, respectively. NCM was diagnosed using echocardiography, multispiral computed tomography (n=77) and magnetic resonance imaging (n=51), increased LV trabecularity was diagnosed according to echocardiography, multispiral computed tomography (n=11), multispiral computed tomography (n=24). DNA diagnostics was carried out according to the NGS method, followed by Sanger sequencing. The examination included the determination of anticardial antibodies, the genome of cardiotropic viruses by PCR, coronary angiography (n=29/2), scintigraphy (n=27/4). A morphological study of the myocardium was performed on 22/6 patients with NCM/increased LV trabecularity (14/6 endomyocardial biopsy, 1 intraoperative biopsy, 3 explanted heart studies, 6 autopsies).Results. Pathogenic mutations were found in 12 (10,3%) patients (MYH7, MyBPC3, LAMP2, DES, DSP, TTNgenes), variants of uncertain clinical significance (VUCS) — in other 5 (4,3%) patients; we detected VUCS in 1 patient with increased LV trabecularity. Familial cardiomyopathy may be diagnosed in 24 patients (22%). The combination of NCM with congenital heart defects was diagnosed in 11 (9,5%) patients. We identified six clinical variants of NCM: asymptomatic (2%), arrhythmic (15%), ischemic (7%), NCM in patients with dilated cardiomyopathy (42%), NCM in patients with acute/subacute myocarditis (12%) and in combination with other primary cardiomyopathies (22%) — hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, restrictive cardiomyopathy, primary myodystrophy, cardiac sarcoidosis, Danon disease. Myocarditis was diagnosed in 51,7% of patients with various forms of NCM and in 59,5% of patients with increased LV trabecularity. The frequency of the main clinical manifestations of NCM (chronic heart failure, various cardiac arrhythmias, thromboembolic complications) and outcomes varied in groups of patients with different variants of the NCM course. In patients with increased LV trabecularity, similar clinical variants were noted with a less severe myocardial dysfunction, rare arrhythmias and embolism. A significant improvement in dynamics of EF and LV end-diastolic diameter was noted only in the group of patients with acute/subacute, most of which received basic myocarditis therapy. In other groups, there was an unreliable improvement.Conclusion. NCM can be detected in a patient of any age with a previously diagnosed heart disease (coronary heart disease, arterial hypertension, congenital heart defects, cardiomyopathy, myocarditis, etc.), and in the absence of any symptoms. Stable clinical forms are characterized by stability over time with a tendency to improvement against the background of complex medical therapy

COVID-19 Pneumonia in Patients with Chronic Myocarditis (HBV-Associated with InfarctLike Debute): Specifics of the Diseases Course, the Role of the Basic Therapy (Part II)

Chronic infectious-immune myocarditis of severe course can potentially be considered as a factor that aggravates the course of new coronavirus disease (COVID-19) and increases the risk of adverse outcomes. The interaction of chronic myocarditis and COVID-19 during long-term immunosuppressive therapy has not been studied. We present a description of a 35-year-old female patient with chronic infectious-immune myocarditis (morphologically confirmed, with a history of infarction-like onset and thromboembolic complications), who had continuous immunosuppressive therapy with methylprednisolone and mycophenolate mofetil. The patient also received new oral anticoagulants and tenofovir (for chronic HBV infection). COVID-19 (SARS-Cov-2 RNA+) was diagnosed in May 2020. Risk factors for the adverse course of coronavirus infection included severe obesity, heart failure, and life-threatening ventricular arrhythmias. Correction of immunosuppressive therapy (withdrawal of the cytostatic agent, administration of hydroxychloroquine) and therapy with levofloxacin, an interleukin-17 inhibitor (netakimab) were performed. The severity of pneumonia and respiratory failure was moderate despite high fever and high levels of inflammatory markers in the blood (including interleukin-6). Signs of exacerbation of myocarditis, increased levels of troponin T and anticardial antibodies (compared with the initial ones) were not found. It can be assumed that supportive immunosuppressive therapy for myocarditis has a positive effect on the course of coronavirus pneumonia and avoids exacerbation of myocarditis. Careful continuation of immunosuppressive therapy with temporary withdrawal of aggressive cytostatics can be recommended in chronic myocarditis. Further study of the features of the course of previous myocarditis and COVID-19 pneumonia is necessary

MYOCARDITIS AS A LEGITIMATE PHENOMENON IN NON-COMPACTION MYOCARDIUM: DIAGNOSTICS, MANAGEMENT AND INFLUENCE ON OUTCOMES

Aim. To evaluate the prevalence of myocarditis in adult patients with non-compaction myocardium (NCM) of the left ventricle (LV), and its influence on the disease course, results of treatment and outcomes.Material and methods. To the study, 103 adult patients included, with NCM, 61 males, mean age 45,6±14,9 y. o. (from 18 to 78). Mean end diastolic LV size was 6,0±0,8 сm, EF LV 38,8±14,5%. Diagnosis of NCM had been done by echocardiography, multispiral computed tomography (n=81) and magnetic resonance tomography (n=39). DNA-diagnostics was performed by NGS method with further Senger sequencing. Pathogenic mutations were found in 9% of patients in the genes MYH7, MyBPC3, LAMP2, DES, DSP, TTN. The investigation also included anticardiac antibodies, genome of cardiotropic viruses by PCR, coronary arteriography (n=26), scintigraphy (n=25). Morphological assessment of the myocardium was done in 19 patients (12 endomyocardial biopsies), 1 intraoperation biopsy, 3 explanted hearts, incl. 2 after biopsy, and 5 autopsies. Mean follow-up 12 [2; 32] months.Results. Myocarditis was found in 53,4%, incl. virus-positive in 32,7% of those, with morphology done for 19 patients (active myocarditis in 10, borderline in 6; with minimal signs of activeness in 3). Viral genome in myocardium found in 8 patients (42,1%). The prevalence of myocarditis 44,4% in an arrhythmic variant of NCM, 12,5% in chronic ischemic, 57,5% in dilation cardiomyopathy, 50,0% in NCM patients with other cardiomyopathies. Special cases were acute/subacute myocarditis in NCM (10,7% of all), acute necrosis (infarction) in 4,9%. Comorbidity with myocarditis in NCM led to significantly more severe LV dysfunction (CHF FC 2 [1; 3] v 1,75 [0; 2], p<0,01, EF 33,8±13,5 v 44,7±13,6%, p<0,001), more prevalent non-sustained ventricular tachycardia (67,3% v 29,3%, p<0,01), proper shocks (38,9% v 0, p<0,05), deaths (16,4 and 4,2%, OR 5,75, 95% CI 1,21-27,43, p<0,05) and transplantation (7,3% v 2,1%, p>0,05). Only in myocarditis patients, as a result of basis (antiviral, immune suppression) and cardiotropic therapy there was significant increase of EF (in acute myocarditis from 25,4±7,9 to 38,6±9,5%, p<0,01), decrease of LV size and pulmonary systolic pressure.Conclusion. Myocarditis is typical phenomenon developing in patients with the primary, i. e. genetically verified NCM. The nature of myocarditis in NCM varies (primary infectious-autoimmune, secondary as a response on genetic/ischemic damage of cardiomyocytes), however regardless of this, it leads to significant worsening of structural and functional parameters, increase of the life-threatening arrhythmias rate, and outcomes (death + transplantation, proper shocks), demanding for active basic therapy

Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry

Aims: Dilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non-familial (sporadic) DCM (SDCM) across Europe. Methods and results: Patients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P\ua0<\ua00.01), had less severe disease phenotype at presentation (P\ua0<\ua00.02), more favourable baseline cardiovascular risk profiles (P\ua0 64\ua00.007), and less medication use (P\ua0 64\ua00.042). Outcome at 1\ua0year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25\u20130.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02\u20131.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P\ua0<\ua00.01) and had higher genetic yield (55% vs. 22%, P\ua0<\ua00.01). Conclusions: We observed that FDCM and SDCM have significant differences at baseline but similar short-term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non-marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence