Vol 91, No 9 (2019)


Fibrinolytics: from the thrombolysis to the processes of blood vessels growth and remodeling, neurogenesis, carcinogenesis and fibrosis

Tkachuk V.A., Parfyonova Y.V., Plekhanova O.S., Stepanova V.V., Menshikov M.Y., Semina E.V., Bibilashvili R.S., Chazov E.I.


One of the most outstanding scientific achievements in the thrombolysis is the development and administration of fibrinolysin - the first Soviet drug that lyses blood clots. Intracoronary administration of fibrinolysin reduced the mortality of patients with myocardial infarction by almost 20%. For his work in this field Yevgeny Chazov was awarded the Lenin Prize in 1982. Over the next decades, under his leadership, the Cardiology Center established scientific and clinical laboratories that created new generations of drugs based on fibrinolytics for treating patients with myocardial infarction, restoration of blood flow in ischemic tissue, and also studying the mechanisms of remodeling of blood vessels involving the fibrinolysis system. It have been found new mechanisms of regulation of the navigation of blood vessels and nerves growth, tumor growth and its metastasis with the participation of the fibrinolysis system proteins. The review reports the role of the fibrinolysis system in the thrombolysis, blood vessels growth and remodeling, neurogenesis, carcinogenesis and fibrosis. The article is dedicated to the 90th anniversary of academician E.I. Chazov.
Terapevticheskii arkhiv. 2019;91(9):4-9
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Preprocedural high - sensitivity C-reactive protein (hsCRP) decrease during intensive atorvastatin therapy: the presumable impact on atherosclerosis progression after coronary stenting

Shchinova A.M., Shlevkova G.V., Filatova A.Y., Potekhina A.V., Osokina A.K., Romasov I.V., Zharova E.A., Noeva E.A., Samko A.N., Masenko V.P., Arefieva T.I., Provatorov S.I.


Proinflammatory status is the risk factor for coronary atherosclerosis progression after coronary stenting (CS). Intensive statin treatment is associated with hsCRP concentration decline. Aim: to evaluate prognostic significance of preprocedural hsCRP level reduction with intensive statin regimen for coronary atherosclerosis progression during one year after CS. Materials and methods. We enrolled 102 patients with stable angina who were on list for scheduled CS. Group I (n=37) patients received atorvastatin 80 mg for 7 days before and 3 months after CS with further dose adjustment according to LDL; group II (n=65) patients received atorvastatin 20-40 mg/day for LDL goal achievement. HsCRP level was assessed at baseline, before CS and after 1, 3, 6 and 12 months. Coronary atherosclerosis progression was defined as new ≥50% stenosis or ≥30% increase of ≥20% pre - existing stenosis according to coronary angiography (CA) 1 year after CS. Results. Baseline concentration of hsCRP was comparable: 0.21 (0.13; 0.38) vs. 0.20 (0.1; 0.44) mg/dl in groups I and II, respectively (p>0.05). In group I significant hsCRP level decrease to 0.14 (0.07; 0.32) mg/dl (p<0.05) was determined after 7 days. Coronary atherosclerosis progression was revealed in 10 (41%) patients in group I and in 20 (47%) in group II according to CA. HsCRP level ≥0.26 was associated with coronary atherosclerosis progression during 12 months (OR 4.2 for total study group, 95% CI 1.4-12.3; p=0.01). Conclusion. Elevated preprocedural hsCRP level is associated with coronary atherosclerosis progression after CS. Intensive atorvastatin regimen for one week before CS leads to preprocedural hsCRP level reduction.
Terapevticheskii arkhiv. 2019;91(9):10-15
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Exercise training and erectile dysfunction in patients after coronary artery bypass grafting

Pomeshkina S.A., Barbarash O.L., Pomeshkin E.V.


Aim: to estimate the effects of exercise training on erectile function after coronary artery bypass grafting. Materials and methods. 114 men with stable coronary artery disease undergoing on - pump coronary artery bypass grafting were examined. Patients with ED were randomized into two groups comparable in the main demographic, clinical and baseline parameters: a group of patients undergoing supervised exercise trainings at the outpatient rehabilitation center (n=53) and a group of patients without any exercise trainings at the outpatient hospital (n=61). Patients were assessed 1, 6 and 12 months after CABG. All patients underwent echocardiography (ECHO-CG), bicycle ergometer test without discontinuation of the drug therapy, measurement of nocturnal penile tumescence (NPT), ultrasound assessment of the cavernous arteries with the further estimation of their endothelial function. Results. In addition to the expected improvements in exercise tolerance, regular cycling exercises led to a significant recovery of erectile function (number and duration of NTP, increased penile blood flow volume, estimated during NTP measurement), improved endothelial function of the cavernous arteries, compared to patients without exercise trainings. However, the obtained effects in the group with exercise trainings were short - term. One year after CABG, the number of NTP and penile blood flow volume were superior in patients undergoing exercise trainings. Differences in other parameters became less reliable between the groups. Conclusion. Aerobic exercise trainings appeared to be effective for optimizing exercise tolerance, erectile and endothelial function, and allow improving the prognosis of these patients and, therefore, are needed to be included in the rehabilitation programs for patients undergoing CABG.
Terapevticheskii arkhiv. 2019;91(9):16-20
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Morphological and Immunohystochemical Characteristics of Aspirated Thrombi in Patients with ST-Elevation Myocardial Infarction

Sisakian H.S., Mkhitaryan A.G., Sahakyan V.G., Kocharyan A.S., Asatryan B.A.


The aim of study was to evaluate the morphological and immunohystochemical characteristics of aspirated thrombi in patients with ST-elevation myocardial infarction undergoing precutaneous coronary intervention to find the possible platelet activation and inflammatory cell involvement in coronary thrombi. Materials and methods. Thrombi collected from 67 patients with ST-elevation myocardial infarction were studied. Macroscopic and immunohystochemical analyses were performed to reveal the cellular components of thrombi. The peroxidase - antiperoxidase immunohystochemical method was applied with monoclonal antibodies to CD4+, CD8+, CD15+, CD63+ and CD105+ using diaminobenzidine agent as a visualization agent to investigate the potential involvement of different cellular subpopulations. Results. The macroscopic examination revealed friable thrombi with apparent laminations (lines of Zahn). Microscopic analysis of thrombi revealed a loose meshwork of fibrin fibers with compact accumulation of activated platelets. The platelets were surrounded by neutrophilic granulocytes.The immunohystochemical analysis confirmed that cell aggregates are consisting of CD 63+ activated platelets and leucocytes. The granulocytes also tested positive for CD15 antigen. The immunohystochemical analysis revealed the presence of CD8+ cytotoxic T-lymphocytes and CD4+ helper T-lymphocytes. No expression of iNOS, CD105 and VEGF was found in the analyzed thrombi. Conclusions. The hystopathological evaluation of thrombi in patients with acute ST-elevation myocardial infarction revealed the presence of activated CD63+ platelets and CD15+ neutrophilic granulocytes. Activated platelets and neutrophils may play a role in thromboinflammatory activation course leading to destabilization of atherosclerotic plaque and development of acute thrombosis in patients with ST-elevation acute myocardial infarction.
Terapevticheskii arkhiv. 2019;91(9):21-25
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Possibilities of cardioselective beta - blocker bisoprolol therapy in patients having coronary artery disease and bronchial asthma

Grigorieva N.Y., Ilyushina T.P., Yashina E.M.


Aim: to compare the antianginal and pulse slowing effects, the impact on the ectopic myocardial activity as well as the safety of the treatment with beta - adrenoblocker bisoprolol, calcium antagonist verapamil and the combination of bisoprolol with amlodipine in patients with stable angina (SA) and bronchial asthma (BA). Materials and methods. The study included 90 patients with SA II-III functional class (FC) having concomitant persistent asthma of moderate severity, controlled, without exacerbation. The patients were divided into three groups with 30 individuals in each one depending on the main antianginal drug prescribed. Group 1 patients received a cardio - selective beta - adrenergic blocker bisoprolol (Concor) at the dose of 5 mg/day, patients of group 2 were treated by a calcium antagonist verapamil at the dose of 240 mg/day, patients of group 3 received combined therapy with bisoprolol at the dose of 5 mg/day and amlodipine at the dose of 5 mg/day given as a fixed combination (Concor AM 5/5). All the patients were investigated by the methods of daily ECG monitoring and respiratory function study (RFS) in addition to physical examination at baseline and after 4 weeks of treatment. Results. After 4 weeks of treatment, patients of group 1 and group 3 did not complain of angina attacks and did not use nitroglycerin unlike patients of group 2. The achieved heart rate (HR) in group 1 patients was 68.6±8.5 beats/min, in group 2 - 74.3±5.6 beats/min, in group 3 - 67.3±4.8 beats/min. A significant decrease in the number of supraventricular and ventricular extrasystoles occurred in patients of group 1 and group 3 only. Thus, the pulse slowing, antianginal, antiischemic and antiarrhythmic effect of the calcium antagonist verapamil, even at the dose of 240 mg/day, is not always sufficient for the patients with SA II-III FC and concomitant BA, unlike therapy with the inclusion of beta - blocker bisoprolol. During the study there was no registered deterioration in the indices of bronchial patency according to the RFS data in the patients of all three groups. Conclusion. In patients with coronary artery disease and concomitant asthma, all three types of pulse slowing therapy do not have any negative effects on bronchial patency. Therapy with the inclusion of beta - blockers (bisoprolol or its combination with amlodipine), in contrast to verapamil, reliably reduces heart rate and the number of supraventricular and ventricular extrasystoles in addition to a good antianginal effect.
Terapevticheskii arkhiv. 2019;91(9):26-31
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Comparative efficacy and safety of enoxaparin followed by warfarin and rivaroxaban monotherapy in the treatment of venous thrombosis in patients after intracardiac catheter interventions

Loginova A.I., Kropacheva E.S., Maykov E.B., Balakhonova T.V., Golitsyn S.P.


Aim: to compare two anticoagulant therapy (ACT) regimens in the treatment of venous thrombosis (VT) in patients after catheter interventions - electrophysiological studies (EFIs) and ablations: enoxaparin followed by warfarin, and rivaroxaban monotherapy. Materials and methods. The study included patients from 18 years and older with heart rhythm disorders and planned catheter ablation. When parietal venous thrombosis (VT) were detected at the femoral vein puncture site, all patients were randomly assigned to two treatment groups. In group I enoxaparin 1 mg/kg was prescribed every 12 hours with switching to warfarin after 7 days with maintenance of the target INR values (2.0-3.0). In group II rivaroxaban therapy was started at a dose of 15 mg twise/day for 21 days with a further transition to a dose of 20 mg/day. The total period of observation and treatment of patients was at least 3 months. Results. 408 patients were observed, 42 (10.3%) patients with parietal VT were divided into two treatment groups. In group I (n=16) complete lysis of VT was noted by the 7th day of treatment in 7 (58.3%) patients, however this scheme was associated with a greater risk of complications (р=0.003) at the puncture site in the form of arteriovenous fistulae (n=1; 8.3%) and intermuscular hematomas (n=4; 25%). In group II (n=26), no complications were noted, the lysis time of VT was on average 21 days (n=18; 69.2%). Complete lysis of VT was noted in both groups at the time of the control observation point (3rd month). Conclusion. The efficiency of the two VT treatment regimens was comparable. Enoxaparin therapy is associated with a high risk of local complications, namely intermuscular hematomas (n=4; 25%) and arteriovenous fistulas (n=1; 8.3%). Rivaroxaban monotherapy is safer (p=0.003); in Group II none of the patients had any complications.
Terapevticheskii arkhiv. 2019;91(9):32-37
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Thrombotic and hemorrhagic complications in atrial fibrillation patients, undergoing elective percutaneous coronary intervention

Krivosheeva E.N., Kropacheva E.S., Panchenko E.P., Samko A.N.


Aim. To evaluate efficacy and safety of reduced dose of direct oral anticoagulants (DOACs) as part of triple antithrombotic therapy in AF patients, undergoing elective percutaneous coronary intervention (PCI), and to identify factors, associated with this strategy. Materials and methods. The study is a cohort analysis of AF patients with AF, who successfully underwent elective PCI and assigned DOACs as part of triple antithrombotic therapy (TAT).Influence of a reduced DOACs dose as a part of TAT on the frequency of thecomposite efficacy endpoint (acute coronary syndrome, ischemic stroke, venous thromboembolic events, cardiovascular death and angina pectoris aggravation/need for unplanned PCI) and safety endpoint (hemorrhagic complications BARC types 2-5) were assessed using the Log-Rank criterion. Results. The study included 124 pts (69.4% women, mean aged 69±8.2 years). Themedian total score CHA2DS2-VASc was 5, the median of the Charlson index composed 7. Half (52%) of AF patients with high risk of thrombotic events after elective PCI received reduced-DOACs dose. Median follow up period was 11.0 month. 17 adverse thrombotic events were recorded during this period, BARC 2-5 bleedings occurred in 27 patients. Reduced DOACs doses in AF patients undergoing PCI were associated with significant increase of thrombotic events during follow up period compared to patients received full DOACs doses (0.79 vs 0.93, Log-Rank p=0.0292). Patients, who received full and reduced DOAC doses, were comparable in the frequency of BARC 2-5 bleedings (0.78 vs 0.75, Log-Rank p=0.06742). Conclusions. The administration of a reduced DOACs dose as a part of TAT in patients with AF, who underwent PCI, was associated with significant increase in the incidence of all thrombotic events, compared to patients, who received full dose of anticoagulants. The number of hemorrhagic complications was comparable.
Terapevticheskii arkhiv. 2019;91(9):38-46
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Cardiogenic shock in patients with acute coronary syndrome (data from Russian Federal Acute Coronary Syndrome Registry)

Sagaydak O.V., Oschepkova E.V., Chazova I.E.


Mortality in acute coronary syndrome (ACS) and its complications remains high, despite significant advances in the treatment of coronary heart disease and its complications. One of the most life - threatening complications of ACS is cardiogenic shock (CS). CS is an extreme degree of acute heart failure and develops on average in 5-8% of patients hospitalized with ACS. In the present work, we analyzed data from Russian Federal ACS Registry - frequency of CS occurrence, treatment methods, and outcomes of ACS complicated by CS. Aim. Assess the quality of medical care in patients with ACS, which complicated by CS, and its compliance with current clinical guidelines. Materials and methods. Data from patients with ACS were exported from the Russian Federal ACS Registry. The study analyzed the data of 29.736 patients with ACS entered into the registry system in the period from 01.01.2018 to 31.12.2018. Of the 29.736 patients with ACS, 824 patients were diagnosed with CS. To assess the quality of care provided to patients with ACS and CS, the main clinical gguidelines were used. Results. The group of 824 patients with ACS and CS was analyzed. Among them patients with ACS with ST segment elevation prevailed - 77.8% (n=641). According to Russian Federal ACS Registry 44.3% (n=365) of patients with ACS and CS received conservative treatment, of which 58.6% (n=108) were with ACS with ST segment elevation. Percutaneous coronary intervention was performed in 39% (n=321) of patients, of whom 89.4% (n=271) of patients with ACS with ST segment elevation. According to the data of this study, thrombolytic therapy was performed in 26.5% (n=218) of patients. Conclusion. The data obtained demonstrated that patients with ACS and CS did not receive optimal medical care and their treatment does not fully comply with modern clinical guidelines.
Terapevticheskii arkhiv. 2019;91(9):47-52
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Treatment of ARVI and influenza in patients with arterial hypertension

Silina E.V., Sitnikov I.G., Fazylov V.C., Yeganyan G.A.


Aim: to study the flow phenomena of influenza and ARVI in patients with arterial hypertension, as well as the effectiveness of antiviral therapy. Materials and methods. Analyzed data was collected during the international multicenter prospective observational FLU-EE study "Treatment of ARVI and influenza in routine clinical practice". The study included 18946 patients with established diagnosis of influenza or ARVI of varying severity. 577 patients 51-70 years old who have a history of arterial hypertension (70% of women) were selected from this cohort. These patients regularly received angiotensin - converting enzyme inhibitors for treatment in monotherapy or in combination with other drugs, used to heal diseases of the cardiovascular system. Patients were divided into two groups depending on the therapy. The first group received symptomatic treatment of influenza and ARVI (comparison group, n=86); the second group received the antiviral drug Kagocel in the complex treatment (n=491). Results. Persons with arterial hypertension and other diseases of the cardiovascular system are at risk for severe flu. The administration of the antiviral drug Kagocel as part of the complex therapy of influenza and ARVI makes it possible to speed up the regression of the intoxication syndrome, reduce the incidence of bacterial complications by 36% and the need for antibiotic therapy by 38%. Moreover, a positive effect was registered both with the early treatment of patients for medical help (by 45%) and with delayed treatment, on the 3rd day and later (by 35%). Conclusion. The use of the antiviral drug Kagocel as part of complex therapy for influenza and other acute respiratory viral infections has shown its effectiveness for different groups of patients, including hypertension, despite the fact that cardiovascular pathology, often combined with comorbid diseases, significantly worsens the course and outcome of ARVI.
Terapevticheskii arkhiv. 2019;91(9):53-61
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Full - transcriptome analysis of miRNA expression in mononuclear cells in patients with acute decompensation of chronic heart failure of various etiologies

Zhirov I.V., Baulina N.M., Nasonova S.N., Osmak G.Z., Matveyeva N.A., Mindzaev D.R., Favorova O.O., Tereshchenko S.N.


It is known that micro RNAs are an important regulatory element in the pathogenesis of many diseases, including cardiovascular diseases. Different levels of expression of these molecules in various pathologies makes miRNA a potential diagnostic and prognostic biomarker. Aim. Analysis of miRNA expression levels in mononuclear blood cells (MBC) of patients with acute decompensation f chronic heart failure (CHF) of various etiologies and evaluation of the possibility of their use as a biological marker. Materials and methods. 7 male patients with acute decompensation of CHF with a reduced ejection fraction (EF), NYHA functional class II-IV (FC) according to NYHA [mean (M) EF 29.2%, standard deviation (SD) 13.27%] in age 38 to 65 years old [median (Me) 58 years]. In 3 patients, heart failure developed as a result of dilated cardiomyopathy (DCMP), in 4 patients - against the background of post - infarction cardiosclerosis of the ischemic nature [group of patients with coronary heart disease (CHD)]. The control group - 5 age - matched (from 41 to 57 years old, Me 49 years old) healthy male volunteers. A complete transcript analysis of miRNA expression in MNCs was performed for all patients and healthy volunteers. Results. Differentially expressed miRNAs were determined in patients with CHF (regardless of etiology) compared with healthy individuals: miR-182, miR-144, miR-183, miR-486-5p, miR-143 (log2FC >1, FDR p - value <0.05). When comparing miRNA profiles in IHD or DCMP groups with miRNA profile in healthy individuals of the control group in IHD group, a significant increase in miR-182, miR-486-5p, miR-183, miR-144, miR-144*, miR-451 expression was detected , miR-143, miR-1180 and a decrease in the expression of miR-204, miR-99a (-1 1, FDR p - value <0.05), and in patients with DCMP there was a decrease in the expression of miR-143 and miR-10b (log2FC <-1, FDR p - value <0.05). Conclusion. Based on the results of full - transcriptome sequencing, miRNAs associated with the development of CHF with a reduced left ventricular EF on the background of the existing post - infarction cardiosclerosis were detected.
Terapevticheskii arkhiv. 2019;91(9):62-67
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Epicardial adipose tissue as a marker of visceral obesity and its association with metabolic parameters and remodeling of the left chambers of the heart in young people with abdominal obesity

Blinova N.V., Azimova M.O., Zhernakova Y.V., Zheleznova E.A., Yarovaya E.B., Orlovskiy A.A., Azimova M.R., Dobrovolskaya S.V., Ternovoy S.K., Chazova I.E.


Aim: to study the correlation of epicardial adipose tissue (EAT) with metabolic parameters, 24-hours profile of blood pressure (BP) and left ventricular remodeling, with the volume of intraabdominal adipose tissue (IAAT), measured by multislice computed tomography (MSCT) in patients with abdominal obesity and metabolic syndrome. Materials and methods: the study included 80 participants with abdominal obesity (waist circumference > 80 cm in women and >94 cm in men) and without cardiovascular diseases and diabetes. Within this study the following examinations were performed: waist circumference and the body mass index measurement, blood sampling and measurements of lipid levels, uric acid, fasting glucose, insulin, HOMA index, 24-hour ambulatory blood pressure monitoring. Left ventricular (LV) mass index, relative wall thickness, LV mass/height index were estimated from echocardiographic data. EAT volume and IAAT was measured by MSCT. All patients was devided in two groups for analysis: 1 (n=28) - patients with isolated abdominal obesity, without metabolic syndrome, age was 37.5±6.43 years; 2 (n=52) - patients with metabolic syndrome, age - 38.8±5.88 years. The control group 0 included healthy individuals (n=13) without obesity, age was 30.5±5.97 years. Results. A positive correlation was found between the volume of EAT with the level of insulin in the blood (r=0.2937, p<0.05), HOMA-IR (r=0.3068, p<0.05), negative correlation - with high density lipoproteins cholesterol (HDL cholesterol; r=-0.2328, p<0.05). The EAT volume correlated with mean diastolic blood pressure at night (r=0.2270, p<0.05). Quantitative analysis by cardiac parameters showed that EAT volume had correlation with the size of the left atrium (r=0.3907, p<0.05), LV mass (r=0.4566, p<0.05), the left ventricular myocardium mass index (r=0.2700, p<0.05) and relative wall thickness(r=0.2991, p<0.05). The EAT volume correlated with the volume of IAAT (r=0.6330, p<0.05), negative correlation - with the ratio of the volume of subcutaneous fat to IAAT (r=-0.4236, p<0.05). Conclusion. In the presented study the EAT volume was associated with the insulin resistance index, metabolic parameters and remodeling parameters of the left heart in young people with abdominal obesity. EAT can be considered as a marker of visceral obesity because it strongly correlated with IAAT.
Terapevticheskii arkhiv. 2019;91(9):68-76
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Features of clinical, functional and hemodynamics profile, medical treatment and prognosis evaluation in patients with inoperable chronic thromboembolic pulmonary hypertension and idiopathic pulmonary arterial hypertension according to the Russian registry

Chazova I.E., Valieva Z.S., Nakonechnikov S.N., Taran I.N., Martynyuk T.V.


Aim: to perform the complex analysis of clinical, functional, hemodynamics profile in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) compared to the idiopathic pulmonary arterial hypertension (IPAH) group at the time of diagnosis verification according to the Russian registry, and to evaluate the features of medical therapy and it’s influence on prognosis in these patients. Materials and methods. In the retrospective study 193 patients with IPAH and 130 patients with inoperable CTEPH older than 18 years were included. All included patients were the participants of Russian registry (www.medibase.pro) in 15 Russian expert centers during the period from 01.01.2012 to 31.12.2018 year. The diagnosis was verified according to the algorithm, reflected in the Russian guidelines on diagnosis and treatment of PH and CTEPH (2016 year). The comparison analysis of clinical, functional, hemodynamics parameters in patients with IPAH and inoperable CTEPH was made. Results. The status of 193 patients with IPAH (32 male and 162 female) and 130 patients with inoperable CTEPH - (40 male and 90 female) was analyzed during the study. The CTEPH patients were older compared to the IPAH patients: 52.2 [41.1; 60.6] and 36.5 [26.8; 36.5] years, respectively. The median period since symptom occurrence till CTEPH verification was 1.08 [0.2; 3.1] years, in IPAH patients - 2.01 [0.6; 4.2] years. More than 80% of inoperable CTEPH patients had III and IV functional class (FC) according to the World Health Organization classification at the time of diagnosis verification versus 61% of IPAH patients. According to echocardiography the level of mean pulmonary arterial pressure was comparable in two groups of PH patients. However in inoperable CTEPH patients the right atrial area was larger. The significantly higher value of mean pulmonary arterial pressure and lower value oxygen saturation of arterial blood according to the right heart catheterization were revealed. The 5-year survival in CTEPH patients, receiving initial dual combination therapy in 75% cases (in 40% - combination of riociguat and iloprost ) was 93% versus 86.5% in patients with IPAH. Conclusion: It was revealed, that inoperable CTEPH patients were significantly older with severe functional and hemodynamics status at the time of diagnosis verification, although with higher level of 5-year survival compared to the IPAH patients according to the Russian registry.
Terapevticheskii arkhiv. 2019;91(9):77-87
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Antihypertensive therapy in men and women in real clinical practice according to the National register

Oshhepkova E.V., Aksenova A.V., Orlovskij A.A., Chazova I.E.


Hypertension is one of the most important risk factors for cardiovascular diseases (CVD) in the world, including Russia. Current Guidelines for the management of arterial hypertension do not include different theatment strategies for men and women. Gender and age analysis of antihypertensive treatmen in men and women could reveal unreasonable and non - optimal treatment in each group. The purpose of this study was to identify the gender features of antihypertensive therapy used by primary care physicians in patients with hypertension. Materials and methods. The study is based on the Arterial Hypertension Registry established in 2012. The methodology of it has been described previously [1]. Medical data from outpatient cards were entered by doctors of 53 city primary care medical centers and 5 cardiology clinics from 22 regions of the Russian Federation. The study included the data of 33 564 patients from 18 years and older with diagnosis of arterial hypertension. Gender, age, height, body weight, smoking status, office blood pressure (BP), laboratory and instrumental examination methods, diagnosed cardiovascular and cerebrovascular diseases and comorbidities in accordance with the International Classification of Diseases of the 10th revision [ICD-10], as well as the treatment (antihypertensive and lipid - lowering therapy) were listed. Results and conclusion. Gender differences in the prescription antihypertensive therapy (AHT) in men and women with hypertension were revealed. Apparently, one of the reasons for these differences is the earlier and more frequent development of cardiovascular and cerebrovascular complications of hypertension in men than in women. Beta - blockers (BB) and angiotensin - converting enzyme inhibitors (ACEi) are more often prescribed to men with hypertension and with coronary artery disease (CAD), myocardial infarction (MI) and chronic heart failure (CHF). Women with hypertension are more often prescribed angiotensin receptor blockers (ARB), thiazide and thiazide - like diuretics. The study also showed non - optimal treatment of patients with hypertension. Insufficient prescription of medication which could improve the prognosis of the disease (ACE inhibitors /ARB, BB, mineralocorticoid receptor antagonist) have been identified in patients with hypertension and CAD, MI, CHF. It is noteworthy that in the some outpatient cards of patients with AH there is no record of AHT prescription: at a young age - in 9.6%, at old age in 15.1% of cards. Despite the fact of high and very high cardiovascular risk of the majority of patients, lipid - lowering therapy (statins) was prescribed insufficiently. The most statin administration was observed in hypertensive patients with coronary artery disease (50.1%) and myocardial infarction (62.7%).
Terapevticheskii arkhiv. 2019;91(9):88-100
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Autoantibodies to M2-cholinoreceptors as a potential development factor of arrhythmia in patients with paroxysmal atrial fibrillation

Mironova E.S., Mironova N.A., Sharf T.V., Efremov E.E., Azmuko A.A., Molokoedov A.S., Zykov K.A., Golitsyn S.P.


Aim. We aimed to assess autoantibodies to M2-cholinoceptors (M2-CR) in patients with paroxysmal lone atrial fibrillation (AF) and in patients with AF and arterial hypertension (AH). Materials and methods. 100 patients with lone AF and 84 patients with AF and AH were included. Patients underwent clinical blood and urinalysis, assessment of biochemistry blood panel, 12-lead ECG, 24-hour Holter monitoring, echocardiography and stress - testing (treadmill or stress - echocardiography). Assessment of IgM and IgG autoantibodies to M2-CR was performed by indirect immunoenzyme assay. The following peptide molecules were used as epitopes for detection of autoantibodies: M1 - amino acid sequence YTVIGYWPLGVVCDL (83-98) of the first extracellular loop of M2-CR; M2 - sequence VRTVEDGECYIQFFSNAAVTFGTAI (168-192) of the second extracellular loop of M2-CR; M3 - sequence NTFCAPCIPNTV (410-421) of the third extracellular loop of M2-CR; M4 - short sequence VEDGECYIQFFS (171-182) of the second extracellular loop of M2-CR; M1+M4 - chimeric molecule formed by sequences of the first and the second extracellular loops of M2-CR connected by disulfide bound YTVIGYWPLGVVCDL + VEDGECYIQFFS (83-98 + 171-182). Results. Autoantibodies to M2-CR were found in 45% patients with lone AF and in 35% patients with AF and AH. In patients with lone AF prevalence of increased IgG to M2-CR were greater than in patients with AF and AH (32% vs 20%; p<0.05). Patients with lone AF had higher prevalence of increased IgG to M1 (44% vs 28%; p<0.05), M2 (44% vs 32%; p<0.05) and M1+M4 (35% vs 23%; p<0.05) sequences. There were no differences in prevalence of increased IgM to M2-CR between the groups. Patients with lone AF had higher prevalence of concomitantly increased levels of IgM and IgG to M2-CR (15% vs 4%; p<0.05). Quantitate analysis demonstrated significantly higher levels of IgG but not IgM to all amino acid sequences in patients with lone AF. Conclusion. High prevalence of increased levels of autoantibodies to M2-CR in patients with paroxysmal AF may suppose an active role of autoimmune processes in arrhythmogenesis.
Terapevticheskii arkhiv. 2019;91(9):101-107
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Endothelial dysfunction in patients with controlled and uncontrolled arterial hypertension

Podzolkov V.I., Safronova T.A., Natkina D.U.


Aim. To conduct a comparative analysis of the level of asymmetric dimethylarginine (ADMA) in two groups of patients with a diagnosis of essential arterial hypertension (AH). Group I - patients with uncontrolled hypertension (UCAH) and group II - patients with controlled course of hypertension (CAH). Materials and methods. The study included 109 patients: group I - 73 patients with UCAH, group II - 36 patients with CAH. Groups were comparable. Clinical, laboratory and instrumental examination was performed, including determination of ADMA concentration in blood plasma. Results. The concentration of ADMA in patients with UCAH was significantly higher than in the group with CAH. In patients with UCAH, a pronounced positive correlation was found between the concentration of ADMA and creatinine level (r=0.615, p<0.05), and a significant negative correlation was identified between the levels of ADMA and the filtration function of the kidneys, estimated using GFR (r=-0.444, p<0.05). As the level of ADMA in the blood increased, a statistically significant decrease in GFR was detected (p<0.05). Also in the group of patients with UCAH, a significant positive correlation of the average strength was found between the concentration of ADMA and progression of stenosis of brachiocephalic arteries (BCA; r=0.5, p<0.05). Conclusion. A significant increase in ADMA level was revealed in patients of both groups compared to the physiological norm (p<0.05), and it was significantly higher in patients with UCAH compared to those in group II, which indicates that UCAH enhances the severity of endothelial dysfunction. Establishing a reliable correlation between the level of ADMA in patients with UCAH with indicators of renal function damage, progression of BCA stenosis indicates the potential use of this substance as a marker of target organ damage and prognosis of the course of the disease.
Terapevticheskii arkhiv. 2019;91(9):108-114
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Endovascular closure of a ventricular septal defect from Takotsubo Syndrome

Zhukova N.S., Merkulova I.N., Shakhnovich R.M., Merkulov E.V., Osiev A.G., Pevzner D.V., Sukhinina T.S., Staroverov I.I.


Takotsubo Syndrome is a transient condition characterized by left ventricular systolic dysfunction. Although the prognosis is excellent in most cases, rare cases of serious complications can occur. We present a case of a 81-year - old woman with Takotsubo Syndrome complicated by ventricular septal rupture that was successfully closed with an occluder Occlutech with good immediate and long - term outcomes.
Terapevticheskii arkhiv. 2019;91(9):115-123
pages 115-123 views

Metastatic lesion of the right atrium with renal cell carcinoma

Isaev G.O., Mironova O.Y., Yudakova M.E., Shakhnovish R.M., Fomin V.V.


Tumors in the heart are rare and difficult to diagnose pathologies. There are primary and secondary tumors, the letter tumors include metastases of other tumors. In this work is presented clinical case of metastatic lesion of the right atrium with renal cell carcinoma. Modern methods of diagnostics of patients with intracardiac formations are discussed.
Terapevticheskii arkhiv. 2019;91(9):124-128
pages 124-128 views

Hypertrophic cardiomyopathy: modern aspects of pharmacologic treatment

Gudkova A.Y., Streltsova A.A., Kostareva A.A.


This article discusses recent advances in understanding genetic basis and classification of hypertrophic cardiomyopathy. Here, we review pharmacologic treatment strategies and new developments in disease - specific management of HCM.
Terapevticheskii arkhiv. 2019;91(9):129-136
pages 129-136 views

The importance of modern high - sensitivity troponin tests in the diagnosis of myocardial infarction without ST-segment elevation

Abaturova O.V., Suplotov S.N., Kremneva L.V., Shalaev S.V.


The literature review presents the characteristics of modern high - sensitivity tests for detection of Tn (hs - cTn) in the blood and the results of large studies on the diagnosis of non segment elevation myocardial infarction (nonSTEMI) using hs - cTn. The results of these studies served as the basis for the development of three - and one - hour diagnostic algorithms nonSTEMI, presented in the recommendations of the European Society of Cardiology 2012 and 2015 and also in fourth Universal Definition of Myocardial Infarction 2018.
Terapevticheskii arkhiv. 2019;91(9):137-144
pages 137-144 views

Galactin-3: diagnostic and prognostic value in patients with chronic heart failure

Aliyeva A.M., Baykova I.E., Kislyakov V.A., Gasanova E.T., Almazova I.I., Pinchuk T.V., Fedulayev Y.N., Zhbanov I.V., Perevertov V.A., Kovtyukh I.V., Nikitin I.G., Reznik E.V.


Now there is a relevant development of the new biomarkers capable to serve as the instrument of early diagnostics of a disease for the purpose of selection of a pharmacotherapy and further monitoring of its efficiency. Galektin-3 is the atypical representative of the family of galektin. Its participation in fibrosis, remodeling of heart, the immunologic answer and inflammatory reactions are shown. Prognostic value is discussed and diagnostic opportunities of Galektin-3 at CHF are widely studied and take root into clinical practice. Now a great deal of research devoted to the studying of Galektin-3, possibilities of its use as a biomarker at diagnostics, forecasting of outcomes and the choice of therapeutic strategy at other cardiovascular diseases has been conducted.
Terapevticheskii arkhiv. 2019;91(9):145-149
pages 145-149 views

Risk stratification methods and their significance in pulmonary arterial hypertension

Avdeev S.N., Tsareva N.A.


Despite significant advances in therapy, pulmonary arterial hypertension (PAH) remains a progressive disease with a poor prognosis. Immediately after establishing the diagnosis of PAH, urgent treatment with PAH-specific therapy is required. Due to the progressive nature of the disease, all patients should be closely monitored and their treatment regimen should be promptly changed according to clinical need. Risk stratification is an important method for informing the clinician and the patient about the prognosis of disease and the choice of therapy methods. The REVEAL scale and the ESC/ERS 2015 risk assessment table are important multifactorial tools for making decisions about the prescription and correction of PAH therapy, as well as for assessment of patients' response to therapy. Current guidelines for PAH indicate that the most important task of treatment of PAH is to achieve the low - risk status.
Terapevticheskii arkhiv. 2019;91(9):150-157
pages 150-157 views

Therapeutic aspects of the choice of antithrombotic therapy in patients with multifocal lesions of peripheral arteries

Oynotkinova O.S., Nikonov E.L., Kryukov E.V., Baranov A.P.


The article discusses the features of the development and course of the atherosclerotic process in various vascular basins. Variability of factors such as local hemodynamics, differences in the structure of the arteries can influence the formation of atherosclerotic plaque and the progression of the atherosclerotic process. A better understanding of the nature and causes of these differences can help improve the tactics of treatment and prevention of vascular complications. Analysis of the results of the COMPASS study (cardiovascular outomes for people using anticoagulation stategies - evaluation of cardiovascular outcomes in patients receiving anticoagulant therapy) showed for the first time the effectiveness of combination therapy using rivaroxaban direct anticoagulant at a dose of 2.5 mg 2 times a day in combination with acetylsalicylic acid at a dose of 100 mg per day. It was shown that, against the background of combination therapy, patients with coronary heart disease or atherosclerotic peripheral artery disease showed a significant decrease in the incidence of events of the primary end point of efficacy: a reduced risk of stroke, cardiovascular mortality and myocardial infarction, and also a reduction in the risk of major lower amputations extremities and total mortality in patients with stable forms of atherosclerosis. The emergence of combination therapy can help to achieve both an improvement in the overall prognosis and the prognosis of limb preservation in patients with multifocal arterial lesion.
Terapevticheskii arkhiv. 2019;91(9):158-164
pages 158-164 views

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