Long-term Results of Drug and Interventional Treatment in Patients with Morphologically Verified Idiopathic Arrhythmias

Aim. To study the late results of medical and interventional treatment in patients with morphologically verified nature of idiopathic arrhythmias.Methods. The prospective study included 20 patients (mean age 43.1±11.3 years, 10 female) with atrial fibrillation (AF), supraventricular and ventricular extrasystole, supraventricular and ventricular tachycardia, conduction disturbance without structural heart changes. In addition to the standard examination, the level of anti-heart antibodies was initially determined; endomyocardial biopsy (EMB) of the right ventricle with PCR study for the viral genome; DNA diagnostics (n=4), coronary angioraphy (n=6), skin biopsy (n=1) were performed. The median follow-up was 134 [128; 138] months.Results. By EMB in the initial examination were diagnosed: active (n=8)/borderline (n=3) infectious immune myocarditis; parvovirus-positive endomyocarditis (n=1); undifferentiated vasculitis (n=2); myocardial vasculitis (n=1); Fabry disease (n=1); arrhythmogenic right ventricular dysplasia (n=1); unspecified cardiomyopathy (n=2). Anti-heart antibodies were the most important in myocarditis diagnosis and monitoring. All patients with myocarditis/vasculitis (n=15) received its basic therapy: acyclovir (n=10); immunoglobulin G 10-12.5 g (n=2); hydroxychloroquine 200 mg/day (n=15); glucocorticoids (n=14); azathioprine 150 mg/day (n=2). The late results were evaluated in all patients with myocarditis. Initially, in 62.5% of patients a resistance of AF to all antiarrhythmic drugs was noted. After treatment the average frequency of AF paroxysms decreased (from 8 [5; 8] to 3 [1,25; 7,75] points). By the end of the follow-up, six patients underwent radiofrequency ablation (RFA) for AF, the full effect was achieved once. All patients without RFA have AF partially or completely resistant to drugs. Two patients (without RFA) died from ischemic stroke/ pulmonary embolism.Conclusion. Using EMB the causes of idiopathic arrhythmias (mainly AF) were diagnosed: immune inflammatory diseases in 75% and genetic in 25% of patients. As a result of complex treatment, the general burden of arrhythmias has decreased. But the presence of myocarditis and primary cardiomyopathy, without reducing the cardiac contractility and dilatation, does not allow achieving a stable antiarrhythmic effect. Lethality for 11 years was 10%. The causes of death were thromboembolic complications

Controversial and open issues of diagnosis and treatment of myocarditis (based on the discussion of Russian national recommendations)

In October 2020, the Russian Ministry of Health approved clinical guidelines for the management of patients with myocarditis. The aim of this review was to highlight controversial and open issues without unambiguous answer or those that were not described in the paper. The review highlights the objective factors that complicate the development of practical guidelines for the management of this category of patients. Comments on the definition and classification of inflammatory heart diseases are given. The approaches to the diagnosis of patients with suspected myocarditis are discussed. Particular attention is paid to the decision-making strategy in selecting optimal therapy in patients with documented myocarditis and the role of endomyocardial biopsy

Rendu-Osler-Weber Disease with High Pulmonary Hypertension and Interstitial Lung Disease

A 64-year-old female with a family history of hereditary hemorrhagic telangiectasia (HHT) was hospitalized due to complaints of dyspnea during light physical exertion and leg edema. HHT was diagnosed at 20 y.o., recurrent nasal bleeding started at age 52, bleedings severity was aggravated by not completely compensated hypertension. At the age of 60, after a massive hemorrhage, she noted the onset of dyspnea, edema, ascites. Diuretics and iron preparations improved her well-being, but from that period onward her heart failure worsened after each massive blood loss. The last major bleeding was before the present hospitalization (Hgb 67 g/l), after which heart failure symptoms significantly deteriorated. Echocardiography showed preserved left ventricular ejection fraction, but revealed high pulmonary hypertension (systolic pulmonary artery pressure 69 mmHg). Chest computed tomography (CT) with contrast showed no evidence of pulmonary embolism, but interstitial lung lesions were detected. Pulse therapy with glucocorticosteroids did not result in positive dynamics at the control CT scan, which allowed to reject a separate interstitial lung disease. As a result of cardiotropic and diuretic therapy, as well as correction of anemia, the patient's condition improved. Macitentan was administered, but the patient refused from it because one of possible side effects was anemia. A year later the patient diedfrom acute progression of pulmonary hypertension. According to the literature, pulmonary hypertension in HHT can have a significant impact on the prognosis and requires timely diagnosis and treatment. Interstitial lung lesions are a manifestation of the underlying disease and does not require special treatment

Director of the Faculty Therapeutic Clinic Nikolay Fedorovich Golubov: Scientific Activity, Last Years of Life and Finding of the Lost Grave (by the 165th Anniversary from Birthday)

September, 2021 marks the 175th anniversary of the opening of the Faculty Therapeutic Clinic (FTC) of the Imperial Moscow University, which is a successor of the First (1805) and Second (1820) Clinical Institutes with their therapeutic beds and chairs, and thus is the oldest therapeutic clinic in Russia. From 1930 the Clinic became part of the newly formed I.M. Sechenov First Moscow Medical Institute (now Sechenov University) and retains continuity to the present day. This publication is one of three research articles prepared by the staff of the Clinic for the anniversary and devoted to little-known pages of biography and scientific activities of the three heads of the FTC at the crucial stages of its history – A.I. Over, G.A. Zakharyin and the last prerevolutionary director – N.F. Golubov

Spectrum of desmosomal gene variations in patients with arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary myocardial disease with a high risk of sudden cardiac death. The most common genetic forms of the disease are associated with desmosomal gene mutations.Aim. To study the prevalence of desmosomal forms of ARVC and to analyze variations in the PKP2, DSG2, DSP, DSC2 and JUP genes in a sample of Russian patients with ARVC.Material and methods. Included patients with ARVC underwent resting electrocardiography (ECG), 24-hour Holter ECG monitoring, echocardiography, chest x-ray, myocardial biopsy (if indicated), contrast-enhanced cardiac magnetic resonance imaging. All patients underwent medical genetic counseling. Mutations in the PKP2, DSG2, DSP, DSC2, and JUP genes was detected using highthroughput sequencing on the IonTorrent platform, followed by Sanger sequencing of uncovered gene regions. The pathogenicity of identified genetic variations was assessed according to modern guidelines.Results. ARVC was established in 80 Russian unrelated patients. More than half of the probands (57%) in the study sample had definite diagnosis of ARVC, while 30% and 13% — borderline and possible ARVC, respectively. A positive family history of heart disease and/or SCD was noted in 30%. Genetic variants of pathogenicity class IV-V were detected in 15 (18,75%) probands in the PKP2, DSG2, DSP genes. The detection of genetic variants of pathogenicity class IV-V was different in the subgroups of patients with varying degrees of diagnosis reliability: 13 probands (28,3%) in the subgroup with definite ARVC and 2 probands (8,3%) in the subgroup with borderline ARVC. No genotype-positive probands were found in the subgroup with possible ARVC. Variations of unknown clinical significance were found in 13 (16,25%) probands.Conclusion. The diagnostic yield of the desmosomal genes PKP2, DSG2, DSP, DSC2, and JUP was 19% with initial diagnosis of ARVC. The detection of mutations was significantly higher in patients with definite ARVC and severe disease manifestations

Evolution of diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy and their application in clinical practice

This article describes evolution of criteria for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The novel diagnostic criteria for ARVD/C published in 2020 are analyzed in detail, among which biventricular and leftdominant arrhythmogenic cardiomyopathy are identified for the first time. The need to develop novel criteria was fed on the accumulation of new data on ARVD/C, in particular, significant advances in magnetic resonance imaging technologies. The novel criteria retained high sensitivity and specificity in relation to traditional right ventricular disease form and became more sensitive in relation to the biventricular and left-dominant arrhythmogenic cardiomyopathy.Nevertheless, the addition of left-dominant disease forms reduces the criteria specificity in general, since left ventricle involvement with a similar clinical performance can have different etiology that goes beyond the ARVD/C, even when mutations are detected in typical genes, which is demonstrated by case reports described in the article. Like the previous two versions, the novel criteria will be fully assessed only with a large sample of patients after their introduction into the routine cardiology clinical practice

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)

Comparative efficacy and safety of mycophenolate mofetil and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis

Aim. To study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis in comparison with a standard combination of corticosteroids and azathioprine.Material and methods. The study included 46 patients aged 18 years and older with severe and moderate lymphocytic myocarditis (men, 34; women 12; mean age, 53,5±13,0 years). The diagnosis was verified using endomyocardial biopsy. Symptom duration averaged 9,5 [4; 20.25] months. All patients had class 3 [2,75; 3] heart failure (HF). The main group included 29 patients who received MM 2 g/day, including six patients — instead of azathioprine, which was canceled due to cytopenia (n=3) or insufficient effect (n=3). The comparison group included 17 patients who received azathioprine 150 [100; 150] mg/day. Patients of both groups also received methylprednisolone at a starting dose of 24 [24; 32] and 24 [24; 24] mg/day and standard HF therapy. In 7/2 patients, the parvovirus B19 genome was detected in the myocardium. In all cases, an increase in anticardiac antibody titers was evidence of immune activity. The average follow-up period was 24 [12; 54] months (at least 6 months).Results. The groups were completely comparable in age, initial characteristics and standard drug therapy. In both groups, a comparable significant increase in the ejection fraction (EF) was noted as follows: from 31,2±7,6 to 44,7±8,3% and from 29±9,1 to 46±11,9% (p<0,001). An excellent response to treatment (an increase in EF by 10% or more) was noted in 68,2% and 66,7% of patients, a good response (by 9-5%) — in 27,3% and 14,3%, a poor response (an increase in less than 5% or a decrease in EF) — in 4,5% and 19,0%, respectively. In both groups, we noted the same significant (p<0,01) decrease in pulmonary artery systolic pressure (36,3±12 to 28,1±6,1 mm Hg in the MM group and from 44,1±8,5 to 30,7±12,1 mm Hg in the azathioprine group), left ventricular (LV) end-diastolic dimension (from 6,4±0,6 to 6±0,7 cm and from 6,2±0,5 to 5,8±0,6 cm), LV end-diastolic volume (from 188,7±55,2 to 178,8±57,1 ml and from 167,8±47,5 to 163,3±61,8 ml), LV end-systolic volume (from 130,3±44,1 to 98,4±32 ml and from 118,1±39 to 94,1±46 ml), left atrial volume (from 98,3±30,3 to 86,7±32,6 ml and from 105±27,4 to 91,2±47,3 ml, p<0,05), as well as mitral regurgitation grade. The incidence of deaths was 2 (6,9%) and 2 (8,7%), transplantation — 1 (3,4%) and 1 (4,3%) patients, death+transplantation end point — 3 (10,3%) and 2 (11,8%) without significant differences between the groups. The presence of the parvovirus B19 genome did not affect the results of treatment. The incidence of infectious complications was comparable in both groups (in one case, MM was completely canceled), no new cytopenia cases were noted during the follow-up period.Conclusion. In patients with moderate and severe virus-negative (except for parvovirus B19) lymphocytic myocarditis, the combination of moderate-dose corticosteroids with mycophenolate mofetil 2 g/day is at least no less effective than the standard regimen of immunosuppressive therapy. There was a tendency towards a more pronounced decrease in anticardiac antibody titers in combination with better tolerance (no cases of cytopenia) in MM group. MM in combination with corticosteroids can be recommended as an alternative treatment regimen for lymphocytic myocarditis

Infective and nonbacterial thrombotic endocarditis in patients with post-COVID-19 viral-immune myocarditis

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)

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