[Long-term treatment of morphologically verified myocarditis: successes and probable errors. Case report].

Diagnosis and treatment of myocarditis can be challenging, including determining indications for heart transplantation. We present a 6-year medical history of a 54 years old patient with severe morphologically verified viral-negative lymphocytic myocarditis and systemic manifestations (onset of hemorrhagic vasculitis) combined with moderate coronary atherosclerosis, which regressed according to repeated coronary angiography. For 5 years, the patient received immunosuppressive therapy with methylprednisolone and azathioprine with a significant improvement. Repeated relapses of atrial fibrillation required correction of basic therapy and plasmapheresis. The disease was complicated by thyrotoxicosis and multi-organ dysfunction; the autopsy showed persistent myocarditis activity. The myocarditis is a chronic condition and requires a review of the treatment strategy at each stage.

[Pericarditis in contemporary therapeutic clinic: nosological spectrum, approaches to diagnosis and treatment].

AIM: To analyze the register of pericarditis in a therapeutic clinic, to evaluate their nosological spectrum, to optimize approaches to diagnosis and treatment. MATERIALS AND METHODS: For the period 20072018, the register includes 76 patients with the diagnosis of pericarditis (average age 53.115.7 years, 2085 years, 46 female). Patients with hydropericardium were not included in the register. Diagnostic puncture of pericardium was carried out in 5 patients, pleural puncture in 11 patients. Morphological diagnostics included endomyocardial/ intraoperative biopsy of myocardium (n=4/2), thoracoscopic/intraoperative biopsy of pericardium (n=1/6), pleural puncture (n=5), transbronchial (n=1), thoracoscopic biopsy of intrathoracic lymph nodes (n=2), lung (n=1), supraclavicular lymph node biopsy (n=1), salivary gland (n=1), subcutaneous fat and rectum biopsy per amyloid (n=6/1). The genome of cardiotropic viruses, level of anti-heart antibodies, C-reactive protein, antinuclear factor, rheumatoid factor (antibodies to cyclic citrullinized peptide), antibodies to neutrophil cytoplasm were determined, extractable nuclear antigens (ENA), protein immunoelectrophoresis, diaskin test, computed tomography of lungs and heart, cardiac magnetic resonance imaging, oncologic search. RESULTS: The following forms of pericarditis were verified: tuberculosis (14%, including in combination with hypertrophic cardiomyopathy HCM), acute / chronic viral (8%) and infectious immune (38%), including perimyocarditis in 77%, pericarditis associated with mediastinum lymphoma/sarcoma (4%), sarcoidosis (3%), diffuse diseases of connective tissue and vasculitis (systemic lupus erythematosus, rheumatoid arthritis, diseases of Horton, Takayasu, Shegren, Wegener, 12%), leukoclastic vasculitis, Loefflers endomyocarditis, AL-amyloidosis, thrombotic microangiopathy (1% each), HCM (8%), coronary heart disease (constriction after repeated punctures and suppuration; postinfection and immune, 4%), after radiofrequency catheter ablation and valve prosthetics (2%). Tuberculosis was the main causes of constrictive pericarditis (36%). Treatment included steroids (n=39), also in combination with cytostatics (n=12), anti-tuberculosis drugs (n=9), acyclovir/ganclovir (n=14), hydroxychloroquine (n=23), colchicine (n=13), non-steroidal anti-inflammatory drugs (n=21), L-tyroxine (n=5), chemotherapy (n=1). In 36 patients different types of therapy were combined. Treatment results observed in 55 patients. Excellent and stable results were achieved in 82% of them. Pericardiectomy/pericardial resection was successfully performed in 8 patients. Lethality was 13.2% (10 patients) with an average follow-up 9 [2; 29.5] months (up to 10 years). Causes of death were chronic heart failure, surgery for HCM, pulmonary embolism, tumor. CONCLUSION: During a special examination, the nature of pericarditis was established in 97% of patients. Morphological and cytological diagnostics methods play the leading role. Tuberculosis pericarditis, infectious-immune and pericarditis in systemic diseases prevailed. Infectious immune pericarditis is characterized by small and medium exudate without restriction and accompanying myocarditis. Steroids remain the first line of therapy in most cases. Hydroxychloroquine as well as colchicine can be successfully used in moderate / low activity of immune pericarditis and as a long-term maintenance therapy after steroid stop.

Morphologically proved ANCA positive Loeffler's pancarditis: medical and surgical treatment.

Loeffler's endocarditis remains is a very rare disease, develops due to eosinophilic inflammation predominantly of the endocardium with an outcome in fibrosis and massive thrombus formation and. He is generally characterized by an unfavorable prognosis. Clinical case of a 42-year-old patient with Loeffler endocarditis is presented. The development of the disease was preceded by a polyvalent allergy, mild dry eye syndrome and pansinusitis with a single eosinophilia of blood up to 16%. The reason for the hospitalization was the appearance of biventricular heart failure. During the previous year, the level of blood eosinophils remained normal, a threefold increase in the level of eosinophilic cationic protein was observed once. A 20-fold increase in the pANCA level, a 2.5-fold increase in the level of antibodies to DNA, an antibody to the nuclei of cardiomyocytes 1:160 were detected. The diagnosis was made on the basis of electrocardiography data (low QRS voltage, atrial hypertrophy), echocardiography, multispiral computed tomography and magnetic resonance imaging of the heart (thickening and delayed contrasting of the endocardium, massive thrombosis of the left ventricular apex with obliteration of its cavity, encapsulated fluid in the pericardium with compression of the right ventricle). Systolic dysfunction, severe signs of restriction and arrhythmias were absent. Trombectomy, tricuspid valve plasty, pericardial resection, suturing of an open oval window were performed. Signs of active inflammation with single eosinophils, vasculitis, perimuscular sclerosis, endocardial sclerosis were detected in morphological and immunohistochemical studies of endo-, myo-, pericardium. Viral genome was not found. The therapy with methylprednisolone 24 mg/day, azathioprine 75 mg/day was started. Six months after the operation, the symptoms of heart failure are completely absent, the thrombosis did not recur.

[Increased myocardial expression of Toll-like receptors 2 and 9 as a marker of active myocarditis and a possible predictor of therapeutic effectiveness]. / Povyshennaia ékspressiia toll-like-retseptorov 2-go i 9-go tipov v miokarde kak marker aktivnogo miokardita i vozmozhnyi prediktor éffektivnosti lecheniia.

AIM: to investigate the myocardial expression of some structural proteins and markers of cellular proliferation and innate immunity for assessing their possible diagnostic and prognostic role in patients with chronic myocarditis. SUBJECTS AND METHODS: The investigation enrolled 23 patients (16 men; mean age, 52.0±12.4 years (range, 27 to 73) with various forms of noncoronarogenic myocardial injury who underwent right ventricular endomyocardial biopsy (n=4), intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their morphological examination, the patients were divided into two groups: 1) 10 patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic pulmonary thromboembolism, presumptively without myocarditis. Along with myocardial histological and immunohistochemical (IHC) examinations, the expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and 9 was determined. Polymerase chain reaction was used to identify whether herpes viruses of and parvovirus B19 genomes were present in the blood and myocardial samples; indirect ELISA was applied to estimate the blood level of antibodies against various cardiac antigens. RESULTS: According to the histological findings, active/borderline lymphocytic myocarditis was diagnosed in all the patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying disease (only in 9 and 7 patients, respectively), viral genome was detected in the myocardium of 15 patients, including in 5 without morphological signs of myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions and the morphological pattern of active myocarditis in the absence of this correlation with the expression level of other studied markers. The expression level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75] and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2 [2; 2] and 4 [3; 4] points, respectively (p<0.001). The expression of TLR2 and TLR9 in patients with borderline myocarditis was lower than in those without myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points), which can reflect cardiomyocyte destruction/depletion at later stages of the disease. There was also a close correlation between the expression level of TLR2 and that of TLR9 (r=0.824; p<0.001) and with Ki-67 levels (r=-0.531 and r=-0.702; p<0.01). There was also a correlation of the expression of the studied markers with viral persistence (desmin), the degree of myocardial dysfunction and cardiosclerosis (c-kit), which calls for further investigations. CONCLUSION: Determination of the myocardial expression level of TLR2 and TLR9 may serve as an immunohistochemical marker for myocarditis and preservation of its activity, which is especially valuable in patients with borderline forms. The marked expression of these markers for innate immunity may reflect both one of the mechanisms of genetic predisposition to myocarditis and its severe course and their secondary activation in the pathogenesis of the disease and is a potential target of therapy.

Exudative-constrictive tuberculous pericarditis in combination with arthritis in cardiologist practice: thoracoscopic biopsy as a diagnosis and treatment method.

AIM: The goal is to present the possibilities of diagnosis verification, the features of the clinical picture of tuberculous pericarditis in the therapeutic clinic and the results of its treatment. MATERIALS AND METHODS: The paper presents clinical observation and a general analysis of 10 cases of tuberculous pericarditis in patients aged 31-79 (mean age 58.0 ± 15.1 years), 6 women and 4 men. Diagnostic puncture pericardium was performed on two patients, pleural puncture - on three Thoracoscopic biopsy of hilar lymph nodes and lung (n=1), pleura (n=1), supraclavicular lymph node biopsy (n=1). Dyskin test was carried out, as well as sputum examination, multispiral computed tomography, oncological search. RESULTS: A 31-year-old patient with a massive effusion in the pericardial cavity, pleural lesion, arthritis of the left knee joint, whose results of the pericardial effusion and sputum were not diagnosed, tuberculosis was detected only with thoracoscopic biopsy of the lung and intrathoracic lymph nodes; the treatment via prednisolone and subtotal pericardectomy was performed. Among 10 patients with MSCT of the lung, changes were noted in general, but in only one case they were highly specific. Diaskin test is positive in 70%. In the study of punctata, bronchoalveolar flushing, Koch bacteria were not detected; at sputum in microscopy and biological sample BC was detected in two patients. The lymphocytic character of effusion in the pericardium / pleura is noted in 4 out of 5 cases. At a biopsy of lymphonoduses and a lung at 2 patients the picture of a granulomatous inflammation with a caseous necrosis. Pericarditis was predominantly large (from 2 cm and more) effusion, signs of constriction were noted in 50% of patients. CONCLUSION: Tuberculosis is one of the frequent causes of pericarditis in the Moscow therapeutic clinic. The most lymphocytic effusion with fibrin and the development of constriction. The negative results of all laboratory tests for tuberculosis do not exclude a diagnosis, It is necessary to use invasive morphological diagnostics, including thoracoscopic biopsy.

[Efficiency of immunosuppressive therapy in virus-negative and virus-positive patients with morphologically verified lymphocytic myocarditis]. / Éffektivnost' immunosupressivnoi terapii u virus-negativnykh i viruspozitivnykh bol'nykh s morfologicheski verifitsirovannym limfotsitarnym miokarditom.

AIM: To evaluate the efficiency of immunosuppressive therapy (IST) in virus-negative (V-) and virus-positive (V+) patients with lymphocytic myocarditis (LM). SUBJECTS AND METHODS: 60 patients (45 males) (mean age 46.7±11.8 years) with dilated cardiomyopathy (mean left ventricular (LV) end diastolic size (EDS) 6.7±0.7 cm; ejection fraction (EF) 26.2±9.1%) were examined. The diagnosis of active/borderline LM was verified by right ventricular endomyocardial biopsy in 38 patients, by intraoperative LV biopsy in 10, in the study of explanted hearts from 3 patients and at autopsy in 9. The investigators determined the genomes of parvovirus B19, herpes viruses types 1, 2 and 6, Epstein-Barr (EBV), zoster, and cytomegalovirus in the blood and myocardium and, if antibodies were present in the blood, hepatitis B and C viruses, as well as antibodies against antigens in the endothelium, cardiomyocytes and their nuclei, smooth muscles, fibers of the conducting system. IST was used in terms of histological, immune, and viral activities. IST was performed in 22 V+ patients (Group 1) and in 24 V- patients (Group 2); this was not done in 10 V+ patients (Group 3) and V- patients (Group 4). IST comprised methylprednisolone at a mean dose of 24 mg/day (n=40), hydroxychloroquine 200 mg/day (n=20), azathioprine at a mean dose of 150 mg/day (n=21); antiviral therapy included acyclovir, ganciclovir, intravenous immunoglobulin (n=24). The follow-up period was 19 (7.3-40.3) months. RESULTS: The viral genome was detected in the myocardium of 32 patients who made up a V+ group. The degree of histological activity did not differ in relation to the presence of viral genome in the myocardium. The degree of immune activity (anticardiolipin antibody titers) in the V+ patients was as high as that in V- ones. At baseline, the V+ patients had a significantly higher LV EDS and a lower EF than the V- patients. Overall, IST only could lead to a significant increase in EF (from 26.5±0.9 to 36.0±10.8%; p<0.001) and reductions in NYHA functional class from III to II (p<0.001), LV EDS (from 6.7±0.7 to 6.4±0.8 cm; p<0.01), pulmonary artery systolic pressure (from 48.9±15.5 to 39.4±11.5 mm Hg (p<0.01); the IST group had significantly lower mortality rates than the non-IST group (23.9 and 64.3%; p<0.01). At the same time, a significant trend was seen in both V- and V+ patients. The mortality rate in the V+ patients, as a whole, was higher (46.9 and 17.9%; p<0.05). CONCLUSION: IST leads to a significant improvement of functional indices and it is associated with lower mortality rates in both myocardial V- and V+ patients with LM. A more than 10% EF increase in the first 2 months is associated with a good prognosis. The presence of viral genome in the myocardium (primarily herpesviruses rather than parvovirus-19) is accompanied by more severe initial dysfunction, a less pronounced effect of IST, and higher mortality rates. However, the positive effect of IST also persists in V+ patients. No positive changes (a decrease in EF was observed) were absent only in IST-naïve V+ patients.

[Clinical, laboratory and instrumental criteria for myocarditis, established in comparison with myocardial biopsy: A non-invasive diagnostic algorithm]. / Klinicheskie, laboratornye i instrumental'nye kriterii miokardita, ustanovlennye v sopostavlenii s biopsiinym issledovaniem miokarda (algoritm neinvazivnoi diagnostiki).

AIM: To determine the diagnostic value of different clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in patients with the picture of idiopathic arrhythmias, dilated cardiomyopathy (DCM) and in a comparison group when comparing with myocardial morphological examination. SUBJECTS AND METHODS: A study group included 100 patients (35 women; mean age, 44.7±12.5 years) with idiopathic arrhythmias (n=20) and DCM as a syndrome (n=100). All underwent myocardial morphological examination: endomyocardial biopsy (EMB) (n=71), intraoperative biopsy (n=13), study of the explanted heart (n=6), and autopsy (n=11). A comparison group consisted of 50 patients (25 women; mean age, 53.7±11.7 years) with non-inflammatory diseases of the heart (left ventricular end-diastolic dimension <6.0 cm, ejection fraction >50%) who underwent open-heart surgery (n=47), EMB (n=2), or autopsy (n=1). The investigators also performed polymerase chain reaction for cardiotropic viral DNA in the blood and myocardium, anticardiac antibody (ACA) identification, myocardial scintigraphy (n=26), coronary angiography (n=47), magnetic resonance imaging (MRI) (n=25), and multislice computed tomography of the heart (n=45). The diagnostic value of the extended spectrum of clinical, laboratory, and instrumental markers for myocarditis was estimated. RESULTS: Active/borderline myocarditis was diagnosed in 76% of the patients in the study group (75.5% in the arrhythmia subgroup and 76.3% in the DCM one) and in 24.3% of those in the comparison group (p<0.001). A viral genome in the myocardium was detected statistically significantly less frequently in the study group than that in the comparison one (40.2 and 65%, respectively; p<0.01): in 46.6% in the DCM subgroup and 15.8% in the arrhythmia one. An ACA set (sensitivity, specificity, and predictive value of positive and negative test results (45.7, 80, 80.4, and 45%, respectively)) was of the greatest diagnostic importance in identifying myocarditis; antibodies to cardiomyocyte nuclei in a titer of 1:160-1:320 had the highest specificity (93.3%). A specificity above 70% was seen for a full medical history triad (acute onset, an association between onset and infection, a symptom duration of less than one year), systemic immune manifestations, anginas in the history and elevated anti-O-streptolysin levels, systemic blood changes, Q waves/QS complexes on ECGs, local hypokinesias, pericardial effusion, atriomegalia (in arrhythmias), angina/ischemia with intact coronary arteries, and focal perfusion defects during myocardial scintigraphy. A sensitivity higher than 50% was observed for age over 40 years (differential diagnosis with genetic forms), acute onset, a correlation with infection, and delayed contrast agent accumulation, as evidenced by MSCT/MRI. CONCLUSION: When the incidence of myocarditis is similar in the arrhythmia and DCM subgroups, the viral genome detection rate is statistically significantly higher in DCM. Among the non-invasive markers, an ACA set (high sensitivity and specificity) is of the greatest diagnostic value in the diagnosis of myocarditis. The diagnostic rule based on counting the number of scores has been developed, which makes it possible to individually establish the risk of myocarditis in patients with idiopathic arrhythmias and DCM for both the determination of indications for biopsy and the lack of the possibility of its performance. The risk of myocarditis is high if there are 5-7 scores; that is close to 100% if there are 8 scores or more.

[Takayasu's disease in an IgG4-positive patient with tuberculosis, pulmonary hemorrhage, recurrent myocarditis, and transient bilateral visual impairments]. / Bolezn' Takayasu u IgG4-pozitivnogo patsienta s tuberkulezom, legochnym krovotecheniem, retsidiviruyushchim miokarditom i prekhodyashchimi dvustoronnimi zritel'nymi narusheniyami.

Takayasu's disease (nonspecific aortoarteritis) affects the absolute majority of 20-40-year-old women; its most common manifestations include aortic arch branch lesions. The specific features of the described case is the male gender of the patient, signs of mesenchymal dysplasia, a concurrence of tuberculosis, pulmonary hemorrhage, and myocarditis at onset, the presence of IgG4, peculiar ocular symptomatology, and its rapid regression after initiation of therapy.

[Treatment for ventricular arrhythmias in the absence of structural heart disease: from guidelines to clinical practice]. / Lechenie zheludochkovykh aritmii v otsutstvie strukturnoi patologii serdtsa: ot rekomendatsii k klinicheskoi praktike.

AIM: To determine criteria for choosing management tactics in patients with ventricular arrhythmias (VA) in the absence of structural heart disease from the point of view of physicians and patients in clinical practice and to compare the immediate results of antiarrhythmic drug therapy (ADT) and radiofrequency ablation (RFA) with the trends in arrhythmic syndrome in the non-treatment group. SUBJECTS AND METHODS: Examinations were made in 90 patients (23 men and 67 women) (mean age, 44 (31; 57) years) with VA in the absence of structural heart disease. Preference was given to RFA (n = 32 (36%)), ADT (n = 37 (41%)), and follow-up tactics (n = 21 (23%)). At baseline and 1 month, Holter ECG monitoring was done; quality of life (QOL) was assessed; and anxiety and depression levels were detected using the SF-36 and HADS questionnaires. In addition, 71 physicians were surveyed about their preferences to the treatment of VA in individuals without structural heart disease. RESULTS: In the total group of patients, VA was unambiguously accompanied by the symptoms only in 47%. The signs of anxiety and depression were identified in 41 and 14% of cases, respectively. The efficiency of RFA was comparable to that of ADT (p > 0.1): a positive antiarrhythmic effect was observed in 71.9% of the patients in the RFA group and in 67.6% in the ADT group. During one month, 38.1% of the patients in the follow-up group showed a spontaneous substantial reduction in the number of ventricular premature beats (VPBs) or disappearance of unstable ventricular tachycardia (UVT), which met the criteria for a positive effect. At baseline, the QOL indicators on a social functioning scale in the RFA group were worse than those in the ADT group. At the same time, most QOL indicators in the patients who have chosen a wait-and-see tactic were significantly higher than those in the RFA and ADT subgroups. The patients treated with ethacyzin in the ADT group more frequently achieved a positive effect. In the interviewed physicians' opinion, the choice of a tactic depended on the impact of arrhythmia on health status (68%), the number of VPBs per day (61%), and the presence of UVT (56%). RFA or ADT was most often recommended when there were 10,000-15,000 or more VPBs per day ((49 and 35% of the respondents, respectively). 46.5% of the respondents stated that ß-blockers were the drug of choice for idiopathic frequent VPBs. Only 30% of the respondents considered it appropriate to restrict to a follow-up in the presence of asymptomatic VPBs. CONCLUSION: Patient management in clinical practice generally complies with the current guidelines; however, much importance is attached to the severity of arrhythmia (the number of VPBs per day, the presence of UVT) in addition to the presence of symptoms. In the opinion of most physicians, the initiation of treatment is justified when there are 10,000-15,000 and more per day. QOL assessment may be promising in choosing the optimal management tactics for these patients. Treatment should not be initiated immediately in patients with a high level of QOL, especially in those with arrhythmia lasting less than 12 months, by taking into account that there can be a spontaneous improvement in 38% of cases within the next month. The immediate results of ADT and RFA are comparable in patients with VA in the absence of structural heart disease. The Class IC antiarrhythmic drug ethacyzin is the most effective agent that ensures positive changes in arrhythmic syndrome in 66.7% of cases with the rate of side effects being in 17.8%.

[Multislice spiral computed tomography of the heart in dilated cardiomyopathy: possibilities in the verification of myocarditis (in comparison with myocardial biopsy) and in the evaluation of prognosis]. / Mul'tispiral'naia komp'iuternaia tomografiia serdtsa pri sindrome dilatatsionnoi kardiomiopatii: vozmozhnosti v verifikatsii miokardita (po sravneniiu s biopsiei miokarda) i otsenke prognoza.

AIM: To investigate whether intravenous contrast-enhanced multislice spiral computed tomography (computed tomography) (MSCT) versus myocardial morphological examination can diagnose myocarditis and the non-inflammatory causes of dilated cardiomyopathy (DCM) and evaluate prognosis in patients with the latter. SUBJECTS AND METHODS: A study group consisted of 130 patients, including 95 men (46.8±11.9 years), with DCM (mean left ventricular (LV) end-diastolic dimension (EDD), 6.6±0.8 cm; mean LV ejection fraction (EF), 29.8±9.3%; NYHA functional class (FC) III (II; III)). All the patients underwent intravenous contrast-enhanced 320-slice CT of the heart; myocardial morphological examination was made in 48 patients (endomyocardial biopsy in 29 patients, intraoperative biopsy in 7, and autopsy in 9, and study of the explanted heart in 3). In addition, cardiotropic viral DNA in the blood and myocardium and the level of anticardiolipin antibodies were determined; echocardiography (in all the patients), scintigraphy (n = 45), magnetic resonance imaging (MRI) (n = 21), and coronary angiography (CG) (n = 46), and a genetic consultation were performed. A comparison group comprised 20 patients, including 14 men (69.3±9.2 years), with coronary atherosclerosis (40% or more stenoses) according to MSCT findings in the absence of criteria for DCM (mean LV EDD, 4.8±0.5 cm; mean LV EF, 59.4±4.6%). RESULTS: Morphological/comprehensive examination showed that myocarditis as a cause of DCM was diagnosed in 76 (65%) patients; its concurrence with genetic cardiomyopathies was in 17 more patients (17%). MSCT of the heart revealed lower accumulation areas in 2 (1.5%) patients (type 1 based on the proposed rating scale), delayed myocardial contrast agent accumulation (DMCAA) in 81 (62.3%): subendocardial accumulation (type 2) in 8, intramyocardial accumulation in 4 (type 3), subepicardial accumulation in 52 (type 4), and transmural accumulation in 15 (type 5); DMCAA was not noted in 49 patients. DMCAA was not found in the comparison group. As compared with biopsy, the sensitivity, specificity, predictive value of positive and negative results of the tests in detecting active myocarditis for all the types of DMCAA were 77.4, 47.1, 72.7, and 53.3%, respectively; those for types 3-5 of DMCAA were 77.4, 52.9, 75.0, and 56.3%; those in detecting all the morphological types of myocarditis were 68.3, 28.6, 84.8, and 13.3%, and those for types 3-5 were 65.9, 28.6, 84.4, and 12.5%, respectively. Comparison of the data of MSCT and those of comprehensive examination in all the patients with DCM, the diagnostic significance in detecting myocarditis for all the types of DMCAA was 70.6, 67.9, 88.9 and 38.8%, respectively; that for DMCAA types 3-5 was 60.8, 67.9, 87.3, and 32.3%. In the study group, MSCT also identified the non-compacted myocardium (n = 31 (23.8%)), coronary atherosclerosis (n = 31 (23%)), which is confirmed by CG findings in 15 patients. The patients with DMCAA significantly more frequently showed a relationship with previous infection, acute onset, significantly higher NYHA FCs, end-diastolic and end-systolic LV volumes, and insignificantly lower LV EF. During a mean follow-up periods of 12 (6; 37.25) months, the overall mortality rate was 17.7% (23 deaths); the death + transplantation index was 20% (n = 26). All the types of DMCAA were found to be significantly related to prognosis: in the DMCAA group, the mortality rate was 21.5% versus 7.8% in the non-DMCAA group (odds ratio 3.22; 95% confidence interval, 1.02 to 10.21; p < 0.05). CONCLUSION: MSCT with the assessment of delayed contrast enhancement (and simultaneous CT coronary angiography) can be used for the non-invasive diagnosis of myocarditis in patients with DCM, including that in the presence of contraindications to MRI. DMCAA correlates with the presence of myocarditis, its activity, the degree of functional disorders, and prognosis.

[Chronic Heart Failure With Preserved Systolic Function and Reversible Dilatation of Cardiac Chambers].

Diagnosis of dilation (D) cardiomyopathy (CMP) requires exclusion not only of inflammatory and genetically determined forms but also of some rare diseases. This 51 year old patient with history of moderate arterial hypertension approached a cardiologist because of new onset atrial fibrillation and dyspnea. Echocardiography detected dilation of all cardiac chambers with relatively preserved ejection fraction, causing suspicion of DCMP. Among conditions excluded were coronary atherosclerosis, congenital heart defect with left to right shunt, primary pulmonary hypertension, pulmonary embolism, hypertensive heart, tachycardia induced CMP, arrhythmogenic right ventricular dysplasia, noncompaction myocardium. Further examination revealed massive pelvic arteriovenous malformation with branches of right internal iliac artery and inferior mesenteric artery as feeding vessels. This malformation was considered the leading cause of DCMP. Successful multistage embolization of feeding arteries was associated with reduction of cardiac chambers, alleviation of valvular regurgitation and pulmonary hypertension, restoration of sinus rhythm. Presentation of this case is followed by discussion of possible mechanisms of heart failure with high cardiac output and preserved systolic function in patients with arteriovenous malformations with left to right shunt. Approaches to interventional treatment of these malformations are also discussed.

[Idiopathic arrhythmias: possibilities of complex nosological diagnosis, and differentiated treatment].

AIM: of the study was to elucidate nosological nature of "idiopathic" arrhythmias by means of complex clinical-morphological examination and to assess efficacy of differentiated (including etiotropic and pathogenetic) treatment. MATERIAL AND METHODS: We examined 190 patients (117 women, mean age 45.33 ± 14.84 years) with "idiopathic" arrhythmias: atrial fibrillation (38.9%) (AF,) and flutter (11.1%), supraventricular (44.7%) and ventricular (55.3%) extrasystoles (SVE and VE), bouts of ventricular tachycardia (15.8%), atrioventricular block (22,6%) et al. Mean number of antiarrhythmic drugs per patient was 3 (from 1 to 8). Examination included Holter ECG monitoring, echocardiography, determination of anticardiac antibodies (97.4%) and markers of cardiotropic viruses (87.4%), treadmill test (26.3%), transesophageal cardiac pacing (12.1%), electrophysiological investigation (10%), multispiral computed tomography (22.1%), magnetic resonance tomography (21.6%), scintigraphy (27.4%), coronary angiography (10.0%), endomyocardial biopsy (EMB) (10.0%), DNA diagnostics (8.9%). RESULTS: EMB revealed immune-inflammatory (myo/endocarditis, systemic/myocardial vasculitis) or genetic pathology in 78.9 and 21.1% of cases, respectively. Level of anticardiac antibodies (including specific antinuclear factor) most closely correlated with EMB findings. On the basis of comparison of EMB data with data of complex examination we created algorithm of nosological diagnostics in "idiopathic" arrhythmias. According to nosology all patients were distributed in the following way: 1) chronic infectious-immune myocarditis (n=144, 75.7%), morphologically verified in 14, viral in 27 patients; 2) genetic cardiomyopathy (n=15, 7.9%), morphologically verified in 4, virus positive in 1 (arrhythmogenic right ventricular dysplasia, non-compaction myocardium, Fabri disease, Brugada syndrome, undetermined); in 4 patients mutations in plakophilin 2, desmoglein, desmin, -galactosidase A genes were found; 3) combination of genetic diseases with myocarditis (n=18; 9.5%) including viral (n=3); 4) isolated myocardiodystrophy (tonsillogenic< dyshormonal, n=3, 1.6%); 5) proper idiopathic arrhythmias (n=10, 5.3%). Therapy of myocarditis included antiviral (43.2%) and immunosuppressive (76.3%) drugs. Cardiotropic and antiarrhythmic therapy was also administered. Only in patients with myocarditis it was possible to withdraw effective antiarrhythmic (16.7%) and to improve effect of previously ineffective drugs. Surgical treatment (implantation of pacemaker or cardioverter-defibrillator, radiofrequency ablation) was more frequently used in patients with genetic (39.4%) and idiopathic arrhythmias (53.8%) than in patients with myocarditis (16.0%). CONCLUSION: Etiology of idiopathic arrhythmias can be established in most cases. Their main causes are immune-inflammatory diseases, genetic cardiomyopathies and their combination. Therapy of myocarditis improves antiarrhythmic activity of treatment, in some patients allows to withdraw antiarrhythmic drugs, decrease requirements in surgical treatment and to optimally prepare patients to radiofrequency ablation.

[Possibilities myocardial biopsy in the diagnosis of myocarditis verification in patients with idiopathic arrhythmias].

UNLABELLED: Aim of the study was to elucidate nosological nature of "idiopathic" arrhythmias by means of right ventricular endomyocardial biopsy (EMB) and to assess effect of etiotropic and pathogenetic treatment. MATERIAL AND METHODS: We included into this study 19 patients (mean age 42.6 +/-11.3 years, 9 women) with atrial fibrillation (AF, n = 16), supraventricular (n = 10) and ventricular (n = 4) extrasystoles (SVE and VE), supraventricular (n = 2) and ventricular (n = 1) tachycardia (SVT and VT), left bundle branch block (LBBB, n = 2), atrioventricular block (n = 2) without structural changes of the heart. In addition to standard examination we performed the following tests: determination of IgG to herpes and Coxsackie B virus, polymerase chain reaction (PCR) for DNA detection of human herpesviruses 1, 2, and 6, Epstein-Barr virus, Varicellae-zoster virus (human herpesvirus 3) and cytomegalovirus in blood; determination of anticardiac antibodies; EMB with subsequent PCR-diagnostics including that of parvovirus B19 and pathomorphological study. DNA diagnostics (n = 4), coronary angiography (n = 6), skin biopsy (n = 1) and some other studies were also performed when indicated. RESULTS AND CONCLUSIONS: Histological picture was abnormal in all cases. Nosological diagnosis was established in all patients: infectious-immune myocarditis (n = 11), parvovirus positive endomyocarditis (n = 1); systemic vasculitis (n = 2); myocardial vasculitis (n = 1), Fabri disease (n = 1), arrhythmogenic right ventricular dysplasia (ARVD, n = 1), undetermined genetic cardiomyopathy (n = 2). Level of various anticardiac antibodies including antinuclear factor with bovine heart antigen was most valuable for diagnosis of myocarditis (sensitivity 78.6%, prognostic value of positive result 91.7%). The following therapy was used in patients with myocarditis/vasculitis: intravenous or oral acyclovir (n = 10), gabreglobine (n = 2), meloxicam (n = 12), hydroxychloroquine (n = 15 for 15 [7.0; 24.] months), glucocorticosteroids (n = 14 for 18 [4.0; 25.5] months), azathioprine (n = 2). Mean duration of follow up was 4 years (48 [31; 62] months). At baseline 62.5% of patients with AF were resistant to all antiarrhythmic drugs. Treatment of myocarditis resulted in significant reduction of mean frequency of attacks of AF from 8 to 3 points, more than in 40% of patients AF emerged less than once a month and 1 patient had no attacks at all. Disappearance of tachycardia dependent LBBB was also noted. Cardioverter defibrillator and cardiac pacemaker were implanted to patients with ARVD and Fabri disease, respectively. EMB helped to establish immunoinflammatory and genetic diseases as causes of idiopathic arrhythmias (in 78.9 and 21.1% of patients, respectively). Antiviral immunosuppressive therapy of myocarditis allowed to increase efficacy of antiarrhythmic therapy in resistant patients and when necessary to optimize their preparedness to interventional treatment.

[Arrhythmogenic right ventricular dysplasia: polymorphism of clinical manifestations].

We observed 15 patients with arrhythmogenic right ventricular dysplasia (ARVD): 9 with definite and 5 with probable ARVD (modified European Criteria, 2010). Eight patients had typical ARVD (frequent right ventricular extrasystoles, nonsustained right ventricular tachycardia without heart failure with or without myocarditis). Five patients had ARVD with progressive heart failure (right- or biventricular with or without myocarditis). Two patients had full scale arrhythmic form (sustained right ventricular tachycardia without or with right ventricular dilation, with or without myocarditis). In 3 cases diagnosis was confirmed morphologically or with DNA-diagnostics. This material allowed us to highlight the following specific points related to diagnostics of ARVD. Detection of fat at MRT is not obligatory for diagnosis, fat can be detected by MSCT; ventricular arrhythmias can move backwards in the picture of the disease; leading clinical manifestation can be unexplained right ventricular insufficiency; ARVD can be combined with other genetic cardiomyopathies as well as with infectious immune myocarditis (up to 50% of patients); elevated titer of anticardiac antibodies is not characteristic for isolated ARVD; myocardial biopsy allows to verify both ARVD and concomitant myocarditis. The paper also contains discussion of the role of myocarditis in various forms of ARVD and possibilities of its diagnosis and treatments.

[Noncompaction myocardium as a primary phenomenon or consequence of myocardial dysfunction: clinical masks of the syndrome].

Noncompaction myocardium (NCM) is a genetic heterogeneous primary cardiomyopathy which affects both children and adults and can be either isolated or combined with other congenital heart disorders. It has common pathogenesis of symptoms but is distinguished by pronounced clinical polymorphism. We have observed 25 adult patients (15 men, 10 women aged from 20 to 62 years, mean age 42.9+/-13.3 years) with NCM syndrome. Heart failure have been found in 96% of patients (functional class [FC] I in 7, II - in 6, III in 7, and IV - in 4 patients). Ninety two percent of patients have ventricular extrasystoles, 32% - atrial fibrillation, 28% - FC I-III angina. Mean end diastolic left ventricular dimension is 6.5+/-0.8cm, ejection fraction 29.7+/-13.0%, mean pulmonary artery pressure - 42.6+/-13.5 mm Hg. Intracardiac thrombosis have been found in 24% of patients. In 7 patients morphological study of myocardium has been performed. NCM syndrome was diagnosed at initial investigation just in 1 case. We distinguished the following clinical masks (variants of diagnosis) of NCM: 1) clinically not manifest, is revealed at accidental examination (4%); 2) exists under mask of "idiopathic" rhythm disturbances (8%); 3) has a mask of ischemic heart disease; 4) is revealed in patients with acute or subacute myocarditis (12%); 5) has a mask of dilated cardiomyopathy (52%); 6) NCM in patients with other primary cardiomyopathies (hypertrophic, restrictive, genetic myopathy, arrhythmogenic right ventricular dysplasia). Combination of NCM with congenital heart defects has been found in 20% of patients. In 56% of cases myocarditis was diagnosed (it was viral in no less than 44%). Only in 32% of patients it is possible to consider presence of isolated NCM syndrome. This paper contains discussion of problems of diagnostics (including morphological) and treatment in the presented group of patients, significance of myocarditis for development of decompensation, role of NCM in patients with other primary cardiomyopathies, possibility of compensatory (secondary) character of NCM in severe systolic dysfunction.

[Successful treatment of massive thrombosis of the vena cava inferior with nephrotic syndrome and chronic bilateral pulmonary artery thromboembolism in a patient with genetic thrombophilia].

A case is reported of a 23-year-old male patient who developed, after severe blunt injury of the lumbar region, massive thrombosis of the vena cava inferior (VCI), both renal veins, bilateral pulmonary artery thromboembolism (PATE), nephrotic syndrome (NS). In spite of anticoagulant therapy, the condition of the patient progressively aggravated for 1.5 year: thrombosis involved the ileac and femoral arteries on the right, thrombus floated in the right atrium with PATE recurrent episodes, pulmonary hypertension reached 120 mm Hg with formation of decompensated cor pulmnonale, proteinuria and hypoalbuminemia deteriorated, anasarca edema developed Multigenic thrombophilia was diagnosed (1 homozygous and 5 heterozygous mutations). A radical one-stage operation was successful: thromboectomy from the VCI, right ileac and left renal veins, thrombendarterectomy from the pulmonary arteries, suture of the interatrial septum defect, installation of cava-filter After the operation pulmonary pressure lowered to 40-45 mm Hg, right heart volume normalized, immunosuppressive therapy with prednisolone and cyclosporine led to nephropathy remission. The discussion covers mechanisms and factors (including genetic) of thrombosis progression, correlations between intravascular thrombosis, NS and chronic glomerulonephritis (possible NS development due to bilateral thrombosis of the renal veins and nephropathy role in thrombosis progression), approaches to conservative and surgical treatment of such patients. Global experience in conduction of pulmonary thrombendarterectomy and thrombectomy from VCI is reviewed (one-stage operations were not described earlier).

[Primary lymphoma of the heart: difficulties in diagnosis and treatment].

Primary lymphoma of the heart (non-Hodgkin's lymphoma primarily of B-cells affecting first the heart and pericardium) is a rare disease which accounts for 1.3-2.0% of all primary tumors of the heart. A case is reported of a 43-year-old male patient with a cardioverter-defibrillator implanted at the age of 38 years for management of ventricular tachycardia paroxysms and AB-block of the second-third degree. The patient also had hypertrophic cardiomyopathy, moderate pressure gradient on the pulmonary artery valve and pericardial effusion. Later he had two cardiac tamponades (serous punctuate). From the age of 42 years breathlessness, right ventricular wall thickness, right heart pressure and pulmonary artery pressure aggravated. The patient has undergone ballon plastic surgery of the pulmonary artery valve. At the age of 43 computed tomography detected massive tumor of the heart and mediastinum first diagnosed as sarcoma but later specified as lymphoma. Endobronchial biopsy specimens contained the tissue of diffuse large B-cell lymphoma, the liver and lymph nodes were also involved. After the first course of effective polychemotherapy (CHOP) the patient died of mesenterial thrombosis. Diagnostic difficulties and problems of treatment policy are discussed.

[Dilated cardiomyopathy as clinical syndrome: experience with nosological diagnostics with biopsy and treatment approaches].

AIM: To study possibility of nosological diagnosis in patients with dilated cardiomyopathy (DCMP) with use of myocardial biopsy. MATERIAL AND METHODS: The trial enrolled 62 patients (23 females) with DCMP syndrome (end diastolic left ventricular size > 5.5 cm, ejection fraction < 55%). Mean age of the patients was 46.0 +/- 12.8 years. The examination included diagnosis of viral infections (Herpes virus, parvovirus B19), measurement of anticardial antibodies titer, 99Tc-MIBI single photon emission computed tomography of the myocardium, multislice computed tomography, MRT of the heart, coronarography, morphological study of the myocardium (n=20) with application of polymerase chain reaction (PCR) for H.simplex viruses of types 1, 2 and 6, herpes zoster, Epstein-Barr, cytomegalovirus, parvovirus B-19, adenoviruses. The control group (20 operated patients with valvular heart disease and coronary heart disease) was examined for viral genome in the blood and myocardium. RESULTS: Complex examination of DCMP patients showed the following distribution by nosological entuities: myocarditis (n=41, 66.1%) including virus-positive (n=14), primary DCMP (n=16, 25.9%) including with non-compact myocarditis (NCM) in 3, with debute at delivery of the child--in 3. Arrhythmogenic right ventricular dysplasia combined with viral myocarditis (n=2), genetic myopathy (n=1) and Takayasu disease (n=1) combined with NCM, isolated NCM (n=1) were diagnosed in the rest cases. Morphological investigation of the myocardium was made in 20 patients: diagnosis of myocarditis and primary DCMP were made in 70% (including in 2 patients with CHD) and 20%. Detection of viral genome was 20 and 15% in the study and control group, respectively, in the myocardium--in 57.9 (test for parvovirus B19 was not made in 26%) and 65.0% (complete diagnosis). All the virus-positive patients with DCMP were diagnosed to have signs of active/borderline myocarditis. Diagnostic criteria and poor prognosis factors were defined. CONCLUSION: The nosological diagnosis of DCMP was made in all the examinees basing on the complex of clinical, case history and device evidence. The diagnosis was morphologically verified in 33.9% patients. Treatment approaches are developed.

[The Faculty Therapy Clinic in the formation of clinical teaching of internal medicine: on the occasion of the 250th anniversary of the I. M. Sechenov Moscow Medical Academy].

The V. N. Vinogradov Faculty Therapy Clinic of the Imperial Moscow University (IMU) (then Moscow State University--I. M. Sechenov Moscow Medical Academy) was opened under this name in 1846 simultaneously with the Surgery Clinic on Rozhdestvenka Street. The paper shows the continuity of the idea for bedside clinical teaching, whose need was clearly realized just by S. G. Zybelin and which was first done in practice by his follower and the first Director of the Clinical Institute, IMU, F. G. Politkovsky, as well as that of specific forms of implementing of this idea. It is shown that just early internal medicine teaching provided the principles that were stated by M. Ya. Mudrov and that subsequently formed the basis of a course taught at the Department of Faculty Clinic. The original teaching of a theoretical course without a clinic one at the Department of Particular Pathology and Therapy, which was stipulated by the 1835 Charter, gradually lost its importance as clinical teaching was formed. The succession of the Clinical Institute and the Faculty Clinic was also shown in the staff the director of the newly-opened Clinic and Therapy Department Professor was A. I. Over, M. Ya. Mudrov's favorite disciple and the last Director of the Clinical Institute; the adjuvant teacher at the Therapeutic Department of the Clinical Institute was K. Ya. Mlodzeyevsky. This all permits the V. N. Vinogradov Faculty Therapy Clinic to be regarded a competent descendant of the first clinical institutes. In conclusion, there is a clinical analysis of division of an internal medicine course into faculty and hospital courses at the present stage and prospects for teaching therapy are discussed.

[Severe disseminated constrictive polyserositis in a patient with rheumatoid arthritis].

Constrictive polyserositis (pleuritis, pericarditis) is a syndrome within the underlying disease (tuberculosis, periodic disease, rheumatoid arthritis, systemic lupus erythematosus, asbestos, silicosis, uremia, some genetic diseases), a complication due to chest surgery or radiation or drug therapy, is occasionally idiopathic (fibrosing mediastinitis). There are frequently great difficulties in making its nosological diagnosis. The paper describes a patient in whom the onset of disease was exudative pleurisy with the signs of constriction, arthralgias; pleural punctures provided serous exudates with 80% lymphocytes. A year later there was ascitis and shin and foot edemas, which concurrent with hepatomegaly and cholestasis was regarded as cryptogenic liver cirrhosis. The signs of constrictive pericarditis were further revealed. The disease was complicated by the development of pulmonary artery thromboembolism (PATE) (which required the use of warfarin) and hemorrhagic vasculitis. Therapy with metipred in combination with isoniazid yielded a slight effect. The diagnoses of tuberculosis, liver cirrhosis, and autoimmune hepatitis, systemic vasculitis were consecutively rejected; the diagnosis of rheumatoid polyarthritis with systemic manifestations was made, by taking into account persistent arthalgias with the minimum signs of arthritis, noticeably increased C-reactive protein, rheumatoid factor, and cyclic citrullinated peptide antibodies (CCPA); plasmapheresis, therapy with metipred and methotrexate, and subtotal pericardectomy were performed. Constrictive polyserositis concurrent with PATE, hemorrhagic vasculitis (probably, drug-induced one), and hepatic lesion has been first described in a CCPA-positive patient with rheumatoid arthritis in the presence of moderate true arthritis (during steroid therapy).