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To assess the association of serum tetranectin levels with cardiac remodeling parameters and to evaluate its prognostic role in women with anthracycline-related cardiac dysfunction (ARCD) and without previous cardiovascular diseases (CVD) during 24-month follow-up period. A total of 362 women with primary diagnosed breast cancer who were planned to be treated with anthracyclines were examined. At 12 months after chemotherapy completion, all women were examined and ARCD was diagnosed in 114 patients. After 24 months of follow-up, all patients with ARCD were divided into 2 groups: group 1 comprised women with the adverse course of ARCD (n = 54), group 2 comprised those without it (n = 60). In group 1, the levels of tetranectin were lower than group 2 by 27.6% (p < 0.001) and the patients without ARCD by 33.7% (p < 0.001). In group 1, the levels of tetranectin decreased (p < 0.001) from 11.8 (7.1; 14.3) to 9.02 (5.3; 14.6) pg/mL at 24 months. Moreover, in group 2 (p = 0.871) and in patients without ARCD (p = 0.716), they did not change. The tetranectin values were the independent predictor (odds ratio 7.08; p < 0.001) and its levels ≤ 15/9 ng/mL (AUC = 0.764; p < 0.001) were identified as the predictors for the adverse course of ARCD. NT-proBNP levels did not show the prognostic role, but the addition of NT-proBNP improved prognostic value of analysis (AUC = 0.954; p = 0.002). The cut-off values of tetranectin were established as predictor for adverse course of ARCD, when NT-proBNP was not. The combined use of tetranectin and NT-proBNP demonstrated higher diagnostic value for prediction of adverse outcomes., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Objective: The objective of the study was to evaluate the prognostic role of myocardial flow reserve (MFR) and myocardial blood flow (MBF) estimates obtained with dynamic cadmium-zinc-telluride (CZT) imaging in the development and progression of heart failure with preserved ejection fraction (HFpEF) in patients with nonobstructive coronary artery disease (CAD) during a 12-month follow-up period., Patients and Methods: A total of 112 patients (70 men; median age of 62.5 [57.0; 69.0] years) with nonobstructive coronary artery disease were enrolled in the study. Dynamic CZT-SPECT, echocardiography, and coronary CT angiography studies were performed baseline., Results: Distribution of patients was performed by adverse events: group 1 comprised patients with adverse outcomes (n = 25), and group 2 comprised those without it (n = 87). Based on receiver operating characteristic analysis, the levels of MFR ≤1.62 (area under the curve [AUС], 0.884; Р < 0.001), stress-MBF ≤1.35 mL/min per gram (AUС, 0.750; Р < 0.001), and NT-proBNP ≥760.5 pg/mL (AUС, 0.764; Р = 0.001) were identified as cutoff values to predict adverse outcomes. Univariate analysis revealed that type 2 diabetes mellitus ( P = 0.044), the levels of MFR ≤1.62 ( P = 0.014), stress-MBF ≤1.35 mL/min per gram ( P = 0.012), NT-proBNP ≥760.5 pg/mL ( P = 0.018), and diastolic dysfunction ( P = 0.009) were potential risk factors for the development and progression of HFpEF. Multivariate analysis demonstrated that the values of NT-proBNP ≥760.5 pg/mL (odds ratio, 1.87; 95% confidence interval, 1.17-3.62; P = 0.027) and MFR ≤1.62 (odds ratio, 2.801; 95% confidence interval, 1.19-6.55; P = 0.018) were independent predictors of adverse outcomes., Conclusions: Our data suggest that reduced MFR ≤1.62 obtained with dynamic CZT imaging and overexpression of NT-proBNP ≥760.5 pg/mL can individuate patients at high risk of development and progression of HFpEF during a 12-month follow-up period, independently of baseline clinical parameters and imaging variables., Competing Interests: Conflicts of interest and sources of funding: This study was funded by the grant from the President of the Russian Federation (MK-4257.2022.3). The authors have no conflicts to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim      To evaluate the predictive significance of gene polymorphism in endothelin-1 type 2A receptor, NADPH oxidase, p53 protein, endothelial nitric oxide synthase, caspase 8, interleukin-1β, tumor necrosis factor-α, superoxide dismutase-2, glutathione peroxidase-1, β1-adrenoceptor, angiotensin-converting enzyme, and matrix metalloproteinase-3 (MMP-3) genes in evaluating the risk of anthracycline-induced cardiotoxicity (AIC) in women without concurrent cardiovascular diseases (CVD).Material and methods  This study included 176 women aged 45.0 [42.0; 50.0] years with breast cancer without concurrent CVD who were scheduled for polychemotherapy (PCT) with anthracycline antibiotics. Echocardiography was performed for all patients at baseline and at 12 months after the end of PCT course. Genetic polymorphism was determined with the polymerase chain reaction.Results At 12 months, all patients were in remission of the underlying disease. They were retrospectively included into 2 groups: 1st group, 52 patients with AIC and 2nd group, 124 women without AIC symptoms. The development of AIC was associated with the presence of the p53 protein gene Arg / Arg genotype (odds ratio (OR), 2.972; p=0.001), NOS3 gene T / T genotype (OR, 3.059; p=0.018), NADPH oxidase gene T / T genotype (OR, 2.753; p=0.008), GPX1 gene C / C genotype (OR, 2.345; p=0.007), MMP-3 gene 5A / 5A genotype (OR, 2.753; p=0.008), and ADRB1 gene G / G genotype (OR, 3.271; p=0.043).Conclusion      Evaluation of genetic polymorphism in p53 protein (rs1042522), NOS3 (rs1799983), NADPH-oxidase (rs4673), GPX1 (rs1050450), ADRB1 (Arg389Gly, rs1801253), and MMP-3 (rs3025058) genes can be recommended for use prior to starting chemotherapy in women with breast cancer without CVD for assessing the risk of AIC. A maximum risk of cardiotoxicity is associated with the presence of the p53 protein gene Arg / Arg genotype and NOS3 gene T / T genotype.

To evaluate the myocardial flow reserve (MFR) and myocardial blood flow (MBF) parameters in patients with heart failure with preserved ejection fraction (HFpEF) and to assess their relationship with the severity of HF and the levels of soluble ST2 (sST2). A total of 59 consecutive patients (median age of 65.0 (58.0; 69.0) years) with non-obstructive coronary artery disease (CAD) and preserved EF were enrolled. Serum levels biomarkers were measured by enzyme immunoassay. MBF and MFR parameters were evaluated by dynamic CZT-SPECT. All patients were divided into two groups: group 1 comprised patients (n = 41) with HFpEF, and group 2 comprised those (n = 18) without HFpEF. In group 1 global MFR (gMFR) values were lower by 27.8% (p = 0.003) than in group 2. The values of gMFR correlated with NT-proBNP (r = - 0.290) and sST2 (r = -0.331) levels. Based on ROC-analysis, gMFR ≤ 2.27 (AUC = 0.746; p < 0.001) were associated with the presence of HFpEF. In patients with HFpEF (n = 41) the values of gMFR were related to NYHA classes (p < 0.001) and the parameters of diastolic dysfunction (p < 0.001). The values of gMFR ≤ 2.27 may be used for the evaluation of microvascular changes in patients with HFpEF and non-obstructive CAD., (© 2022. Springer Japan KK, part of Springer Nature.)

Objective: To evaluate role of molecular (endothelin-1, soluble Fas-L, NT-proBNP, TNF-α, interleukin-1β,) and genetic factors (NOS3 (rs1799983), EDNRA (C + 70G, rs5335), NADPH oxidase (C242T, rs4673), p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522), NOS3 (Glu298Asp, rs1799983), Caspase 8 (CASP8, rs3834129 and rs1045485), interleukin-1β gene (Il-1β, rs1143634), TNF-α gene (rs1800629), SOD2 (rs4880), GPX1 (rs1050450) in development of anthracycline-induced cardiotoxicity (AIC) in women without cardiovascular diseases., Methods: A total of 176 women with breast cancer and without cardiovascular diseases who received anthracyclines were enrolled in the study. After the 12 months of chemotherapy (CT), all patients were divided into two groups: group 1 ( n  = 52) comprised patients with AIC, group 2 ( n  = 124) comprised those without it., Results: Based on ROC-analysis, levels of endothelin-1 of ≥9.0 pg/mL (AUC of 0.699), sFas-L of ≥98.3 ng/mL (AUC of 0.990), and NT-proBNP of ≥71.5 pg/mL (AUC of 0.994;) were identified as a cut-off values predicting AIC during 12 months after CT. Whereas, NT-proBNP and sFas-L were more significant predictors than endothelin-1 ( p  < 0.001). The development of AIC was significantly related to Arg/Arg of p53 protein gene (OR = 2.972; p  = 0.001), T/T of NOS3 gene (OR = 3.059, p  = 0.018), T/T of NADPH oxidase gene (OR = 2.753, p  = 0.008), and C/C of GPX1 (OR = 2.345; p  = 0.007)., Conclusion: Evaluation of polymorphisms genes of p53 (rs1042522), NOS3 (rs1799983), GPX1 (rs1050450), and NADPH oxidase (rs4673) can be recommended before CT for the risk assessment of AIC development. The serum levels of NT-proBNP and soluble Fas-L after CT may be considered as non-invasive biomarkers for prediction of AIC development during the 12 months.

Objective: To evaluate the role of matrix metalloproteinases (MMP)-2 and 9 and the gene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) in the course of anthracycline-induced cardiotoxicity (AIC) in women without previous cardiovascular diseases (CVD) during 24-months., Methods: A total of 114 women (47.0 [44.0; 52.0] years old) with AIC of NYHA class I-III who received doxorubicin for breast cancer were enrolled., Results: After 24 months patients had breast cancer remission and were divided into 2 groups: group 1 comprised women with adverse course of AIC (n = 54), group 2 comprised those without it (n = 60). Serum levels of MMP-2 were higher by 8% (p = 0.017) MMP9 by 18.4% (p < 0.001) in group 1 than in group 2. In group 1 the levels of MMP-2 increased (p < 0.001) from 376.8 (329.5; 426.7) to 481.4 (389.8; 518.7) pg/mL, and MMP-9 increased (p < 0.001) from 23.6 (21.4; 24.6) to 26.0 (23.3; 27.0) pg/mL at 24 months. In group 2 the both MMP-2 and MMP-9 level decreased at 24 months. Based on ROC-analysis, the levels of MMP2 ≥ 388.2 pg/mL (AUС = 0.64; р = 0.013) and MMP-9 ≥ 21.25 pg/mL (AUС = 0.9; р < 0.001) were identified as predictors for adverse course of AIHF. The presence of C/C genotype of MMP2 (OR = 4.76; p = 0.029) and C/C genotype of MMP-9 (OR = 15.2; p < 0.0001) were related with adverse course of AIHF and higher levels of MMP-2 and MMP-9., Conclusion: Gene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) and serum levels of MMP-2 and MMP-9 levels in women without previous CVD were associated with adverse course of AIC during 24 months., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim      To study the role of soluble ST2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), and С-reactive protein (CRP) in patients with chronic heart failure and preserved left ventricular ejection fraction (CHF with pLVEF) and syndrome of obstructive sleep apnea (SOSA) in stratification of the risk for development of cardiovascular complications (CVC) during one month of a prospective observation.Material and methods  The study included 71 men with SOSA with an apnea/hypopnea index (AHI) &gt;15 per hour, abdominal obesity, and arterial hypertension. Polysomnographic study and echocardiography according to a standard protocol with additional evaluation of left ventricular myocardial fractional changes and work index were performed for all patients at baseline and after 12 months of observation. Serum concentrations of sST2 , NT-proBNP, and CRP were measured at baseline by enzyme-linked immunoassay (ELISA).Results The ROC analysis showed that the cutoff point characterizing the development of CVC were sST2 concentrations ≥29.67 ng/l (area under the curve, AUC, 0.773, sensitivity 65.71 %, specificity 86.11 %; p&lt;0.0001) while concentrations of NT-proBNP (AUC 0.619; p=0.081) and CRP (AUC 0.511; р=0.869) were not prognostic markers for the risk of CVC. According to data of the ROC analysis, all patients were divided into 2 groups based on the sST2 cutoff point: group 1 included 29 patients with ST2 ≥29.67 ng/l and group 2 included 42 patients with ST2 &lt;29.67 ng/l. The Kaplan-Meyer analysis showed that the incidence of CVC was higher in group 1 than in group 2 (79.3 and 28.6 %, respectively, p&lt;0.001). The regression analysis showed that adding values of AHI and left ventricular myocardial mass index (LVMMI) to sST2 in the model increased the analysis predictive significance.Conclusion      Measuring sST2 concentration may be used as a noninvasive marker for assessment of the risk of CVC development in patients with CHF with pLVEF and SOSA within 12 months of observation. Adding AHI and LVMMI values to the model increases the predictive significance of the analysis.

Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases., (© 2021 S. Karger AG, Basel.)

We compared the capability of human fibroblasts to populate porous polycaprolactone (PCL) scaffolds modified during fabrication with surface-active agents Triton Х-100 (type 1 scaffold) and polyvinylpyrrolidone (type 2 scaffold). The mean fiber diameter in both scaffolds was almost the same: 3.90±2.19 and 2.46±2.15 μ, respectively. Type 1 scaffold had higher surface density and hydrophilicity, when type 2 scaffold was 1.6 times thicker. The cells were seeded on the scaffolds by the dynamic seeding technique and then cultured in Petri dishes with nutrient medium in a humid atmosphere. During 3-day culturing, no cell release from the matrix was noted. DAPI staining proved the presence of cells in both scaffolds. However, in type 1 scaffold the cells populated the whole thickness, while in type 2 scaffold, the cells were present only in the superficial layer. These findings suggest that PCL scaffolds modified with Triton Х-100 or polyvinylpyrrolidone are not cytotoxic, but the structure of the scaffold treated with Triton Х-100 is more favorable for population with cells.

Aim: To study the effectiveness of oral alendronate and ibandronate bisphosphonates for the prevention of cardiovascular complications in postmenopausal women with type 2 diabetes mellitus (DM) and osteoporosis during a 12-month prospective observation., Materials and Methods: The study included 86 women with osteoporosis, chronic heart failure (CHF) and type 2 diabetes: the 1st group (n=52) included patients who received basic therapy for heart failure; the 2nd group (n=34) included patients who, in addition to the basic therapy of heart failure, were prescribed alendronic and ibandronic acid preparations for the treatment of osteoporosis. In order to identify the possibility of associating the studied factors with the nature of the course of heart failure, the patients were divided according to the results of a one - year follow - up into two subgroups: subgroup A (n=49) - patients with a favorable course of the disease and subgroup B (n=37) - patients with an unfavorable course of pathology., Results and Discussion: After 12 months, a significant decrease in the levels of cerebral natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-α, and interleukin-1β was found in the group of women treated with bisphosphonates compared to baseline. Significant associations of NT-proBNP levels (p=0.02) and the studied cytokines (p=0.01) with an unfavorable course of heart failure were revealed. A significant association of bisphosphonate therapy with a favorable course of heart failure (p=0.01) was also revealed. The probability of developing adverse cardiovascular events during the year in the treatment of heart failure with basic therapy drugs with additional therapy of osteoporosis with bisphosphonates is significantly (p=0.0025) lower than the treatment of patients with heart failure with only basic therapy and not taking bisphosphonates for the treatment of osteoporosis., Conclusion: In postmenopausal women with associated cardiovascular pathology (CHF, type 2 diabetes and osteoporosis), prophylactic therapy with oral alendronate and ibandronate oral bisphosphonates is effective, reduces the risk of progression of heart failure, inhibits inflammatory mediators, positively affects the combined endpoints of comorbid cardiovascular pathology.

Aims: To study the prognostic significance of polymorphism of the p53 gene (polymorphism Arg72Pro exon 4, rs1042522) on the development of cardiotoxic remodeling of the left ventricle and heart failure., Material and Methods: A total of 176 women with breast cancer who received anthracycline antibiotics as part of polychemotherapeutic treatment regimens were examined. Based on the results of the survey, 12 months after the end of polychemotherapy, patients in the remission of the underlying disease were divided into 2 groups: patients with cardiotoxic remodeling (52 patients) and women with preserved heart function (124 patients). All patients before the start of the course of chemotherapy, in the dynamics of treatment with anthracyclines and after therapy with such were carried out the study of echocardiographic parameters. All the patients were taken genetic material, followed by typing alleles of the gene for the protein p53 (rs1042522)., Results: Analysis of echocardiographic parameters in patients 12 months after the completion of polychemotherapy in comparison with those before treatment showed a significant difference in the final systolic (33 mm [31; 35] and 28 mm [26; 31], p&lt;0.00001) and terminal diastolic dimensions (51 mm [49; 54.5] and 44 mm [42; 48.5], p=0.0003), as well as a significant decrease in the left ventricular ejection fraction (54.5% [51.5; 58] and 65.5% [62; 70], p&lt;0.00001) in the group of women with developed anthracycline cardiotoxicity. The presence of the Arg/Arg genotype was associated with the development of cardiotoxic myocardial damage during polychemotherapy (OR=3.86, 95% C.I.=1.45-10.26, p=0.005). The Pro/Pro genotype has proved to be a protective factor (OR=0.26, 95% C.I.=0.09-0.69, p=0.015). The conclusion. Predicting the cardiotoxicity of chemotherapy using the polymorphism of the p53 gene is an effective measure of early pre-symptom diagnosis of an increased risk of anthracyclineinduced cardiotoxicity.

Aim: To study the role of soluble ST2 (sST2) in patients with coronary artery disease (CAD) and chronic heart failure (CHF) associated with carbohydrate metabolism disorders (impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) in risk stratification of adverse cardiovascular events (ACE) for 12 months of follow-up., Materials and Methods: We enrolled 118 patients with CAD and CHF I-III FC (NYHA) with the ejection fraction of left ventricular of 60 [46; 64] % aged 62.5 [57; 68] years. Serum sST2 levels were measured by enzyme immunoassay., Results: Depending on the presence of carbohydrate metabolism disorders (CMD), the patients were divided into 3 groups: group 1 (n=65) included patients without CDM, group 2 (n=30) included with IGT, and group 3 (n=23) included with type 2 DM. Serum levels of sST2 in patients with CMD were significantly (p=0.011) higher than in patients without CMD, but in subgroups of patients with IGT and type 2 DM, the concentrations of sST2 did not differ. In group 1 sST2 levels were 30.51 [26.38; 37.06] ng/ml, and in group 2 and 3 - 37.97 [33.18; 47.48] and 41.45 [35.27; 50.37] ng/ml, respectively. There were statistically significant differences in the rate of adverse ACE in relation to sST2 levels: in spite of CMD, in subgroups with biomarker overexpression adverse CCC occurred more often (p&lt;0.01). According to the ROC analysis, the sST2 level of 33.14 ng/ml with the sensitivity of 73.3% and the specificity of 75.0% can be considered as a marker of ACE development within 12 months of follow-up (AUC=0.77, 95% CI 0.59-0.89, p=0.002)., Conclusion: In patients with CHF of ischemic etiology, the prognostic significance of sST2 are established as a biomarker of ACE development. In patients with CDM, sST2 levels are significantly higher than in those without CDM that is associated with a higher rate of ACE within 12 months of follow-up.

Diabetes mellitus is a chronic disease requiring lifelong control with hypoglycemic agents that must demonstrate excellent efficacy and safety profiles. In patients taking glucose-lowering drugs, hypoglycemia is a common cause of death associated with arrhythmias, increased thrombus formation, and specific effects of catecholamines due to sympathoadrenal activation. Focus is now shifting from merely glycemic control to multifactorial approach. In the context of individual drugs and classes, this article reviews interdisciplinary strategies evaluating metabolic effects of drugs for treatment of chronic heart failure (CHF) which can mask characteristic hypoglycemia symptoms. Hypoglycemia unawareness and cardiac autonomic neuropathy are discussed. Data suggesting that hypoglycemia modulates immune response are reviewed. The potential role of gut microbiota in improving health of patients with diabetes and CHF is emphasized. Reports stating that nondiabetic CHF patients can have life-threatening hypoglycemia associated with imbalance of thyroid hormones are discussed. Regular glycemic control based on HbA1c measurements and adequate pharmacotherapy remain the priorities in diabetes management. New antihyperglycemic drugs with safer profiles should be preferred in vulnerable CHF patients. Multidrug interactions must be considered. Emerging therapies with reduced hypoglycemia risk, telemedicine, sensor technologies, and genetic testing predicting hypoglycemia risk may help solving the challenges of hypoglycemia in CHF patients with diabetes. Interdisciplinary work may involve cardiologists, diabetologists/endocrinologists, immunologists, gastroenterologists, microbiologists, nutritionists, imaging specialists, geneticists, telemedicine experts, and other relevant specialists. This review emphasizes that systematic knowledge on pathophysiology of hypoglycemia in diabetic patients with CHF is largely lacking and the gaps in our understanding require further discoveries.

Aim: 1) To study the role of soluble ST2 (sST2) in evaluation of left ventricular (LV) myocardial remodeling and 2) to evaluate the predictive value of sST2 for development of adverse cardiovascular events (CVE) during 12 months following myocardial revascularization in patients with ischemic heart disease (IHD) and chronic heart failure (CHF) with preserved LV ejection fraction (EF)., Materials and Methods: The study included 55 patients (42 men) with IHD and NYHA FC I-III CHF with LV EF 63 [59; 65] % aged 65 [58; 69] who were scheduled for myocardial revascularization. Echocardiographic evaluation of myocardial stress and myocardial remodeling indexes was performed for all patients. Content of sST2 was measured using enzyme immunoassay., Results: Group 1 included patients with sST2 overexpression (≥35 ng/ml) (n=26; sST2-43.75 ng/ml) and group 2 - patients with the sST2 expression.

Aim: To study the role of growth factors ((vascular endothelial growth factor (VEGF), platelet derived growth factor AB (PDGF-AB) and basic fibroblast growth factor (FGF-basic)) in the development and progression of chronic heart failure (CHF) in patients with ishcemic heart disease (IHD)., Materials and Methods: We included in this study 94 patients with CHF. The control group comprised 32 persons. Blood serum levels of growth factors were determined at baseline and after 12 months of observation by enzyme-linked immunosorbent assay., Results: VEGF, PDGF-AB and FGF-basic play an important role in the pathogenesis and progression of heart failure in patients with IHD, determining the increased risk of adverse cardiovascular events in this pathology. Serum activity of growth factors characterizes the severity and course of CHF: with disease progression levels of VEGF and FGF-basic decrease and PDGF-AB concentration increases. Initial low level of VEGF expression regardless of the sex of the patient's sex, significantly low level of FGF-basic and significantly high PDGF-AB in men characterizes unfavorable course of CHF., Conclusion: A correlation has been established between blood serum levels of VEGF, PDGF-AB and FGF-basic and severity and course of CHF.

Aim: to reveal the specific features of Fas ligand-mediated ischemic myocardial remodeling and those of chronic heart failure (CHF) development during a 12-month prospective follow-up., Subjects and Methods: A total of 94 patients with ischemic CHF were examined and divided into 3 groups according to NYHA Functional Class (FC): 1) FC II CHF in 35 patients; 2) FC III CHF in 31; 3) FC IV CHF in 28. According to the results of the 12-month follow-up, the patients were randomized into 2 groups: A) 49 patients with a favorable course of cardiovascular disease and B) 45 patients with its poor course. Serum soluble Fas ligand (sFas-L) levels were measured by enzyme immunoassay., Results: In the patients with CHF, the baseline sFas-L levels substantially exceeded that in the control group by 3-6 times (p<0.01). In the men with the poor course of CHF, the baseline serum sFAS-L levels (85.94±4.14 pg/ml) were significantly higher than that in the favorable CHF group (107.33±5.13 pg/ml; р=0.0015). ROC analysis of the sensitivity and specificity of cardiovascular risk stratification according to sFAS-L levels revealed the high prognostic value of this marker - ROC-Area±S.E. was 0.75±0.05 (95% confidence interval, 0.60 to 0.81; p=0.0005). There was a statistically significant moderate correlation of left ventricular (LV) ejection fraction with sFAS-L concentrations and a moderate direct correlation between serum sFAS-L concentrations and LV remodeling parameters., Conclusion: The serum level of sFas-L determines the development of ischemic LV remodeling and the severity of CHF, by increasing in proportion to the degree of disease progression. The determination of serum sFas-L levels assists in objectively estimating the severity of apoptosis and may be an important prognostic test to assess the course of CHF in patients with coronary heart disease.

Aim: To study the impact of a polymorphic variant of the matrix metalloproteinase-3 (MMP-3) gene on the development and course of chronic heart failure (CHF) in patients with coronary heart disease., Subjects and Methods: A total of 277 patients with New York Heart Association (NYHA) Functional Class (FC) II-IV CHF were examined. MMP-3 -1171 5A/6A genetic polymorphism was studied by polymerase chain reaction. A control group included 136 patients (mean age 53.6 ± 4.8 years) with no signs of cardiovascular diseases, as evidenced by the examination., Results: The frequency of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene proved to be higher in the patients with CHF than that in the control group. Thus, the variability of the 5A allele (odds ratio (OR), 1.39; 95% confidence interval (CI): 1.033 to 1.869; p = 0.03) and the 5A/5A genotype (OR, 2.15; 95% CI: 1.131 to 4.070; p = 0.02) was associated with increased risk for CHF. There were significant differences in the frequency of MMP-3 alleles and genotypes in relation to FC of CHF. The frequency of the 5A/5A genotype was substantially higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (32.8% versus 15.2%; p = 0.039). The frequency of the 5A allele was significantly higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (55.5% and 39.3%; respectively; p = 0.019). Thus, the carriage of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene is a risk factor of severe CHF., Conclusion: The determination of MMP-3 -1171 5A/6A polymorphism may be recommended for the early prediction of a risk for the development and severe course of CHF.