[A rare variant in the TTR gene (p.E112K) is associated with systemic amyloidosis and a new symptom - skin hyperemia in response to ethanol intake: family segregation analysis, literature review, and a clinical case. Case report].

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.

[The levels of certain circulating microRNAs in hypertrophic cardiomyopathy are associated with echocardiographic parameters].

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease; it is characterized by left ventricular (LV) hypertrophy that cannot be explained by hemodynamic causes. It is believed that sarcomere dysfunction underlies the pathogenesis of this disease, however, only half of patients with the HCM phenotype have mutations in sarcomere-encoding genes. HCM is distinguished by both high genetic and clinical heterogeneity and therefore more studies are seeking to investigate a regulation of gene expression in HCM and how the abnormalities in this process can affect disease phenotype. One of the levels of regulation of gene expression - a post-transcriptional level - is mediated by short non-coding microRNAs that inhibit protein synthesis. AIM: To identify the correlations between levels of circulating microRNAs, previously shown to be associated with HCM, and clinical parameters of HCM patients. MATERIALS AND METHODS: Correlation analysis of miR-499a-5p, miR-454 and miR-339-5p plasma levels and clinical parameters of 33 HCM patients, examined from 2019 to 2021, has been performed. RESULTS: Variants in HCM-associated genes were found in 49% of patients. There were no clinical differences between genotype-positive and genotype-negative patients. MiR-499a-5p level correlated with LV ejection fraction, miR-454 level - with LV diastolic function parameters and miR-339-5p level - with left atrium dimension. CONCLUSION: Levels of certain circulating microRNAs correlate with echocardiographic parameters in HCM patients.

[Molecular cardiology: from decoding the genetic nature and mechanisms of the diseases development to the introduction into the clinic].

In recent decades, advances in molecular biology have led to a change in understanding the inheritance mechanisms and development of cardiological diseases of predominantly genetic origin, such as hypertrophic and dilated cardiomyopathies, familial hypercholesterolemia, etc. This knowledge made it possible to develop fundamentally new drug interventions. Programs for detecting cardiac diseases of predominantly genetic origin have been created, including genetic counseling and testing. Competence in this area is becoming a necessary part of a cardiologist's job.

[Practical guidelines for the diagnosis and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM or transthyretin cardiac amyloidosis)].

This paper summarizes the data from updated international protocols and guidelines for diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). The invasive and non-invasive diagnosis techniques and their combinations are briefly reviewed; the evidentiary foundations for each diagnostic option and tool are analyzed. The paper describes a customized algorithm for sequential diagnosis and differential diagnosis of patients with suspected ATTR-CM with allowance for the combination of clinical signs and diagnostic findings. Along with the awareness of primary care providers about the red flags of the disease and visualization criteria, as well as providing information to the patients about the possibility of performing therapy of ATTR amyloidosis and the risks of delayed diagnosis, the proposed algorithm enables timely patient routing and prescribing specific treatment.

[Left ventricular global function index as a predictor of adverse cardiovascular events in patients with acute coronary syndrome].

Aim      To evaluate the prognostic significance of the left ventricular global function index (LV GFI) in patients with acute coronary syndrome (ACS) using echocardiography (EchoCG).Material and methods             The LV GFI is an index that integrates LV cavity volumes, stroke volume, and myocardial volume. This study included 2169 patients with ACS (1340 (61.8%) men) aged 64.1±12.6 years from two observational multicenter studies, ORACLE I and ORACLE II. 1800 (83 %) cases were associated with increased concentrations of myocardial injury markers, including 826 (38.1 %) cases of ST segment elevation myocardial infarction (MI). The observation was started on the 10th day of clinical condition stabilization and lasted for one year. EchoCG was performed with evaluation of LV GFI, which was calculated as a ratio of LV stroke volume to LV global volume. The LV global volume was calculated as a sum of mean LV cavity volume (LV end-diastolic volume + LV end-systolic volume / 2) and LV myocardial volume.Results The main outcome of the study was all-cause death (n=193); recurrent coronary complications (n=253) were analyzed separately. The only EchoCG parameter indicating an adverse outcome during the one-year follow-up was a LV GFI decrease to below 22.6 % with a sensitivity of 72 % and a specificity of 60% (area under the curve, AUC=0.63). A LV GFI <22.6 % was an independent predictor of all-cause death (p=0.019) along with age (p=0.0001), history of MI (p=0.034), and presence of heart failure (HF) (p=0.044), diabetes mellitus (p=0.012), and peripheral atherosclerosis (p=0.001). The LV GFI <22.6 %, (p=0.044), heart rate upon discharge from the hospital (p=0.050), history of MI (p=0.006), presence of HF (p=0.014), and peripheral atherosclerosis (p=0.001) were also independent predictors for recurrent coronary complications. Decreased LV GFI was associated with the risk of fatal outcomes independent of the LV ejection fraction at baseline.Conclusion      In patients with ACS, the left ventricular global function index is an independent predictor for all-cause death and recurrent coronary complications and may be used for risk stratification.

[The Risk of Developing Ischemic Stroke in Patients After Exacerbation of Ischemic Heart Disease].

Aim      To develop a model for evaluating the risk of stroke in patients after exacerbation of ischemic heart disease who were admitted to the hospitals included into a vascular program.Materials and methods This study included 1803 patients with acute coronary syndrome (ACS) from four institutions of Moscow, Kazan, Astrakhan, and Krasnodar where the vascular program was established. Mean age of patients was 64.9±12.78 years, 62,1 % of them were men. The patients were followed up for one year after the discharge from the hospital. External validation of the developed prognostic model was performed on a cohort of patients with ACS included into the RECORD-3 study.Results During the follow-up period, 42 cases of ischemic stroke were observed. The risk of ischemic stroke was associated with the presence of atrial fibrillation (odd ratio (OR) 2.640; р=0.037), diabetes mellitus (OR 2.718; р=0.041), and chronic heart failure (OR 7.049; р=0.011). Protective factors were high-density lipoprotein cholesterol >1 mmol/l (OR 0.629; р=0.041), percutaneous coronary intervention during an index hospitalization (OR 0.412; р=0.042), anticoagulant treatment (OR 0.670; р=0.049), and achieving the blood pressure goal (OR 0.604; р=0.023). The prognostic model developed on the basis of regression analysis showed a good predictive value (area under the ROC curve, 0.780), sensitivity of 80 %, and specificity of 64.6 %. The diagnostic value of other scales for risk assessment was somewhat lower. The area under the ROC curve was 0.692±0.0245 for the GRACE scale and 0.708±0.0334 for CHA2DS2­VASc. In the external validation of the scale based on data of the RECORD-3 study, the diagnostic value was lower although satisfactory as well (area under the ROC curve, 0.651); sensitivity was 78.9 %, and specificity was 52.3 %.Conclusion      The study resulted in development of a simple clinical scale, which will probably allow identifying groups at risk of stroke more precisely than with standard scales.

[Changes in the management of patients with acute coronary syndrome - have the disease outcomes changed?]

Aim        To analyze results of changing the management tactics in patients with acute coronary syndrome (ACS) in clinical practice from 2004 through 2018 expressed as improvement in prognosis.Material and methods        Results of two observational studies were analyzed: ORACLE I (2004-2007), which included 1193 patients with ACS (mean age, 61.1±11.69 years; men, 63.3 %) and ORACLE II (2014-2017), which included 1652 patients from 4 vascular centers (mean age, 64.61±12.67 years; men, 62.3 %).Results   Patients included into the ORACLE II study in 2014 were significantly older and the proportion of patients with diabetes mellitus was greater than in the ORACLE I study (14.7 and 22.6 %, respectively). After matching the groups by major clinical characteristics, it was found that introducing the invasive management tactics for ACS patients was associated with a reduced rate of all-cause death (from 8.2 to 6.1 % for one year), a tendency towards decreased number of coronary death cases (from 5.6 to 4.0 %), and a decrease in risk of recurrent coronary complications (from 17.4  to 7.7 %).Conclusion            Implementing the vascular program statistically significantly decreased the total death rate for at least one-year observation in comparable patient groups.

[Recommendations of the Eurasian Arrhythmology Association (EURA) for the diagnosis and treatment of patients with arrhythmias and conduction disorders during the COVID-19 pandemic].

The beginning of 2020 was characterized by the development of a new coronavirus pandemic (COVID-19). Information about the epidemiology, etiology, pathogenesis, clinical and laboratory diagnostics, as well as prevention and therapy for this disease is constantly being expanded and reviewed. The COVID-19 pandemic creates the need for the emergence of new conditions of specialized care for patients with heart rhythm and conduction disorders [1]. These recommendations are intended for general practitioners, internists, cardiologists, electrophysiologists/arrhythmologists, cardiovascular surgeons, functional diagnostics doctors, anesthesiologists-resuscitators, laboratory diagnostics specialists, health care organizers in the system of organizations and healthcare institutions that provide specialized care to patients with heart rhythm and conduction disorders.

[Participation of Sphingolipids in the Pathogenesis of Atherosclerosis].

Lipid metabolism disorders are the most significant risk factor of development of cardiovascular diseases (CVD). In the process of diagnosing ischemic heart disease and other cardiovascular pathologies, levels of total cholesterol, low- and high- density lipoprotein cholesterol, triglycerides are determined. However, in recent years, close attention has been paid to the intersection of the metabolic pathways of the biosynthesis of cholesterol and sphingolipids. Sphingolipids - a group of lipids, which include a molecule of aliphatic alcohol sphingosine. This group includes sphingomyelins, cerebrosides, gangliosides and ceramides, sphingosines and sphingosine-1-phosphate (S-1-P). Ceramides and sphingosines have pro-apoptotic properties, and S-1-P protects cells from apoptosis. Particular attention as inducer CVD attracts ceramide. It has been established that aggregated lipoproteins isolated from atherosclerotic zones are enriched with ceramides. The level of ceramide and sphingosine increases with ischemia/reperfusion of the heart, in the infarction zone and in the blood, and also in hypertensive disease. S-1-P has a pronounced cardioprotective properties. Its content sharply decreases with ischemia and myocardial infarction. S-1-P performs a special function in the structure of high-density lipoproteins (HDL), being one of the main lipid components of these lipoproteins, which determines their multiple functions. Recently, work has been underway to create drugs that can correct the metabolism of S-1-P. The most successful drugs are those that use the S-1-P receptor as a target, since all of its actions are carried out through receptors. Increasing ceramide and sphingosine and reducing blood plasma level of S-1-P can be an important factor in the development of atherosclerosis. It is proposed to use the determination of the level of sphingolipids in blood plasma for early diagnosis of cardiac ischemia and in arterial hypertension. Chromatography-mass spectrometry has been suggested as the main method for testing these lipids.

[External validation of the ORACLE bleeding risk score using the database of the RECORD 3 registry].

AIM: To validate a domestic scale for assessment risk of bleeding ORACUL (ОРАКУЛ) based on an independent sample of patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: External validation of the ORACUL score was carried out using database of an independent observational study RECORD-3 which comprised data from all patients hospitalized for 1 month (march-april 2015) in 47 centers of 37 cities in 21 regions of Russia. Total number of included patients was 2370, mean age 64.2±11.96 years, 821 patients (34.6%) had ST-elevation, other patients - non-ST elevation ACS. RESULTS: The following bleeding events were registered in RECORD-3: bleedings during hospitalization (n=34, 1.43%), inhospital bleedings requiring withdrawal of antithrombotic treatment (n=16, 0.68%), inhospital bleedings, which required drug or surgical treatment or hemotransfusion (n=16, 0.68%). Forty eight hemorrhagic complications were registered during 6 months of observation after hospital discharge. Diagnostic value of the ORACUL score for estimation of risk of bleedings during index hospitalization was good (C-criterion 0.691±0.050; р<0.001), sensitivity of the model was 58.1%, specificity 79.9%. Earlier on the cohort of patients of the ORACUL study diagnostic value of the score for inhospital bleedings was found to be 0.777±0.046. Difference of diagnostic values was inessential. For estimation of the bleeding risk during 6 months of post discharge observation area under the ROC curve (C-criterion) was 0.628±0.045 (р=0.003), sensitivity and specificity of the model were 53.9 and 73.7%, respectively. On the ORACUL study cohort AUC 0.748±0.048 (р=0.071). CONCLUSION: External validation confirmed that statistical power of the OCACUL score is sufficient for prediction of bleedings during both periods of hospitalization and after hospital discharge.

[Family History of Cardiovascular Disease in Patients With Early Development of Acute Coronary Syndrome].

The aim of the study was to analyze clinical features of patients with premature acute coronary syndrome (ACS) in relation to family history of cardiovascular disease (CVD) and familial hypercholesterolemia (FH). MATERIALS AND METHODS: Of 2832 patients included in ORACUL 1 and ORACUL 2 multicenter observational trials 512 pts who developed premature ACS (≤55 years for men, ≤60 years for women) and had known family history and LDL level were selected for this study. Of these patients 297 had positive family history (51 with FH, 246 no FH), 215 had negative family history. RESULTS: Among patients with positive family history there were more women (31 vs 20.9 %), while among patients with negative family history there were more men (79.1 vs 69 %). The fact of regular alcohol consumption was significantly more frequently observed among patients with positive family history but without FH, compared to patients with positive family history with FH (69.6 vs 47.1 %). Women with positive family history smoked more frequently than females with negative family history (51.1 vs 31.1 %). Among patients with negative family history compared with patients with positive family history there were more people who at admission had hyperglycemia exceeding 11.1 mmol / l (10.3 vs 4.4 %). Multiple vessel disease and coronary calcinosis were present in 73.2 and 24.7 %, respectively, of patients with positive family history, and in 56.9 and 9.8 %, respectively, of those with negative family history. Among patients with positive family history multivessel disease was more frequent in the subgroup with FH, while coronary calcinosis was more frequent in the subgroup without FH. CONCLUSION: Thus, premature development of ACS might be associated not only with genetic factors but also with family history ("inheritance") of adverse habits. Herewith coronary calcinosis is more prevalent in patients with FH.

[Using Necrosis Biomarkers for the Early Diagnosis of Myocardial Infarction in Modern Conditions].

The implimentation of reperfusion treatment of acute coronary syndrome marked the problem of timely allocation of patients with high thrombotic risk. One of the key ways to do this is to use modern biomarkers. The review deals with the peculiarities of using for this purpose the definition of troponin, myoglobin and phosphokinase.

[Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction With ST-Segment Elevation After Prehospital Thrombolysis].

PURPOSE: to analyze results of percutaneous coronary intervention (PCI) in patients with acute ST- elevation myocardial infarction performed after prehospital thrombolysis in real clinical practice. MATERIAL: In the period from 2008 to 2013 144 and 577 patients were subjected to PCI after prehospital thrombolysis with tenecteplase (pharmacoinvasive group - PhG) and primary PCI (PPCIG), respectively. RESULTS: PhG compared with PPCIG contained younger patients (mean age 56.9+/-0.2 and 59.6+/-1.2 years, respectively; p=0.01), and higher portion of men (84.7 and 72.6%, respectively; p=0.003). Frequency of complete occlusion of infarct-related artery in PhG was lower (41.7 and 71.4%, respectively; p< 0.001). Time from onset of pain to administration of a thrombolytic drug was 80 (55; 172) min, PCI was performed in 270 (120; 540) min after thrombolysis. In PPCIG time from onset of symptoms to hospital admission was 120 (60; 230) min, "door-to-balloon" time - 86 (67; 115) min. There was no difference between groups in the composite outcome comprising death, recurrent infarction and stent thrombosis, as well as in frequency of bleeding complications at the puncture site. Rate of major cardiac complications during hospital stay was independently associated with elderly age (odds ratio [OR 1.05; 95% confidence interval [CI] 1.02 to 1.08), previous myocardial infarction (OR 2.21, 95% CI 1.18 to 4.18), and total occlusion of infarct-related artery (OR 4.08, 95%Cl 1.86 to 8.94). Pharmacoinvasive strategy was not associated with reduction of the incidence of major cardiac events (OR 1.25, 95%CI 0.60 to 2.60). CONCLUSION: In settlements with PCI capable hospital primary PCI is clinically and economically justified.Key words: myocardial infarction; pharmacoinvasive strategy; primary percutaneous coronary intervention; prehospital thrombolysis.

[Arterial Hypertension Complicated by Myocardial Hypertrophy and Heart Failure Is Associated With Lower Serum Levels of Vascular Endothelium Growth Factor (VEGF-A165)].

AIM: To study relationships of serum levels of vascular endothelium growth factor with left ventricular (LV) myocardial hypertrophy (H) and signs of heart failure (HF) in patients with arterial hypertension (AH). METHODS: We examined 47 patients with AH and by echo established thickening ( more or equal 16 mm) of LV wall and 47 patients with AH and normal (<12 mm) thickness of LV wall from control group selected according to "head-to-head" principle by age and sex. Serum VEGF-A165 level was measured by sandwich solid-phase immunoenzyme assay. RESULTS: VEGF-A165 level was significantly lower in the group of patients with LVH compared with control group (273.3+/-41.75 vs. 426.6+/-50.00 pg/ml, =0.016). VEGF-A165 level in patients with LVH and NYHA class III HF (140.4+/-51.49 pg/ml) was highly significantly different (p <0.001) from that in in patients without LVH. CONCLUSION: Presence of LVH and HF in patients with AH was associated with lower levels of VEGF-A165 in peripheral blood.

[Atrial Fibrillation in Patients With Chronic Obstructive Pulmonary Disease Is Associated With Polymorphism of Interleukin 6 Gene].

UNLABELLED: It can be suggested that development of atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) is directly related to the system of inflammation. Genetic polymorphism of factors of this system can be one of components of mechanism of AF in COPD. Aim: to elucidate polymorphic markers of genes of factors of the system of inflammation associated with AF in patients with COPD. Material and methods. We examined 208 patients with COPD (52 with and 156 without AF). Examination included spirometry, echocardiography, and study of frequencies of polymorphic markers G(-238)A, G(-308)A of tumor necrosis factor (TNF) gene, C(-819)T of interleukin (IL) 10 gene, G(-174)C of IL-6 gene, rs2228145(AC) of IL-6R gene, and rs2069762(A/C) of IL-2 gene. RESULTS. Factors associated with AF were left atrial volume (odds ratio [OR] 1.021, 95% confidence interval [ClI] 1.004-1.043, p = 0,027), right atrial volume (OR 1.02, 95% CI 1.001-1.040, p=0.021), and carriage of C allele of polymorphic marker G(-174)C of IL-6 gene (OR 6.02, 95% Cl 1.87-19.38, p = 0.003). CONCLUSION: C allele of polymorphic marker G(-174)C of IL-6 gene can be considered to be independently associated with development of AF in patients with COPD.

[Carriage of A Allele of Polymorphic Marker G(-238)A of TNF Gene Is Associated With Unfavorable Prognosis in Patients With Chronic Systolic Heart Failure].

AIM: to elucidate association between polymorphic markers of interleukin-6 (Il-6) and tumor necrosis factor (TNF) genes and unfavorable outcomes in patients with chronic heart failure (CHF). MATERIAL AND METHODS: We determined levels of TNF and Il-6 and genotypes of polymorphic markers G(-238)A of TNF gene (rs361525) and G(--174)C of IL-6 gene (rs1800795) in 151 patients (mean age 64.5 years) hospitalized because of decompensation of systolic CHF (left ventricular ejection fraction ≤ 40%) after stabilization of their state. Unfavorable outcomes were registered during follow-up for 2 years. RESULTS: Mean levels of NT-proBNP, Il-6, and TNF were 2481.1 ± 199.86 fmol/ml, 21.8 7.46 rg/ml, and 10.07 ± 0.65 rg/ml, respectively. 138 (94.4%), 13 (8.6%) and 0 patients were carriers of genotypes GG, AG, and AA of polymorphic marker G(-238)A of TNF gene, respectively; 54 (35.8%), 69 (45.7%), and 28 (18.5%) patients carried genotypes GG, GC, and CC of polymorphic marker G(-174)C gene IL-6, respectively. There was no association between Il-6, TNF levels and carriage of either of genotypes as well as unfavorable clinical course of CHF. Mean survival time before repetitive episode of CHF decompensation (including lethal one) was significantly shorter among carriers of A allele compared with carriers of G allele of polymorphic marker G(-238)A of TNF gene (243 ± 97.7 and 947 ± 78 days, respectively, p = 0.018). Mean time before all cause death was also shorter in carriers of A compared with carriers of G allele (289 ± 122.9 and 1039 ± 73.3 days, respectively, p = 0.03). The studied polymorphism of IL-6 gene had no prognostic value. CONCLUSION: We obtained data on association between carriage of A allele of polymorphic marker G(-238)A of TNF gene and unfavorable prognosis in patients with CHF and inpraired left ventricular systolic function.

[Biomarkers in Heart Failure: Apelin Level Is not Associated With Presence and Severity of the Disease].

We tested possibility of the use of apelin-12 as a biomarker of chronic heart failure (CHF). The study comprised 108 patients with I-IV functional class CHF of various etiology (ischemic heart disease, dilation cardiomyopathy) and 40 healthy volunteers. Blood samples were taken at hospital admission before prescription of pharmacological therapy. In all patients we carried out echocardiography with calculation of end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF). Blood plasma apelin-12 concentration was compared with CHF market NT-proBNP. Mean apelin-12 concentrations were 0.86+/-0.22 hg/ml in healthy volunteers and 0.8+/-0.35, 0.81+/-0.29, 0.68+/-0.38, 0.82+/-0.35 hg/ml in patients with CHF classes I, II, III, IV, respectively. There was no significant differences between appelin-12 concentrations in various classes of CHF. No correlations were found between apelin-12 and EF, EDV, ESV, sex, age, smoking, body mass index, and NT-proBNP level. Concentration of NT pro-BNP level correlated with CHF severity. Thus apelin-12 did not show itself as reliable biomarker of CHF.

[Carriage of A Allele of Polymorphic Marker G(-238)A of TNF-alfa Gene Is Associated With Unfavorable Prognosis in Patients With Chronic Systolic Heart Failure].

AIM: to elucidate association between polymorphic markers of interleukin- 6 (Il-6) and tumor necrosis factor (TNF) genes and unfavorable outcomes in patients with chronic heart failure (CHF). MATERIAL AND METHODS: We determined levels of TNF and Il-6 and genotypes of polymorphic markers G(-238)A of TNF gene (rs361525) and G(-174)C of IL-6 gene (rs1800795) in 151 patients (mean age 64.5 years) hospitalized because of decompensation of systolic CHF (left ventricular ejection fraction less or equal 40%) after stabilization of their state. Unfavorable outcomes were registered during follow-up for 2 years. RESULTS: Mean levels of NT-proBNP, Il-6, and TNF were 2481.1+/-199.86 fmol/ml, 21.8+/-7.46 rg/ml, and 10.07+/-0.65 rg/ml, respectively. 138 (94.4%), 13 (8.6%) and 0 patients were carriers of genotypes GG, AG, and AA of polymorphic marker G(-238)A of TNF gene, respectively; 54 (35.8%), 69 (45.7%), and 28 (18.5%) patients carried genotypes GG, GC, and of polymorphic marker G(-174)C gene IL-6, respectively. There was no association between Il-6, TNF levels and carriage of either of genotypes as well as unfavorable clinical course of CHF. Mean survival time before repetitive episode of CHF decompensation (including lethal one) was significantly shorter among carriers of A allele compared with carriers of G allele of polymorphic marker G(-238)A of TNF gene (243+/-97.7 and 947+/-78 days, respectively, =0.018). Mean time before all cause death was also shorter in carriers of A compared with carriers of G allele (289+/-122.9 and 1039+/-73.3 days, respectively, p=0.03). The studied polymorphism of IL-6 gene had no prognostic value. CONCLUSION: We obtained data on association between carriage of A allele of polymorphic marker G(-238)A of TNF gene and unfavorable prognosis in patients with CHF and inpraired left ventricular systolic function.