Browsing by Author "Radovanovic, Slavica (24492602300)"

Background: The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. Methods. Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. Results: GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype. Conclusions: Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention. © 2014 Suvakov et al.; licensee BioMed Central Ltd.

Aims Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. Methods and results This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n= 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving> 24 million mesenchymal stem cells (n=315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n=157) or sham procedure (n= 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n= 151 sham). The primary efficacy endpoint was a Finkelstein Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann Whitney estimator 0.54, 95% confidence interval [CI] 0.47 0.61 [value> 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370mL (60% of patients) (Mann Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. Conclusion The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted. © The Author 2016.

Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0 031), which was higher when combined with the variant GSTA1∗B allele (OR = 2 2, p = 0 034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 “risk-associated” genotype (OR = 2 8, p = 0 033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2 1, p = 0 056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗ AA/GSTP1∗IleIle carriers (p = 0 021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0 041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0 041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF. © 2019 Dejan Simeunovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0 031), which was higher when combined with the variant GSTA1∗B allele (OR = 2 2, p = 0 034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 “risk-associated” genotype (OR = 2 8, p = 0 033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2 1, p = 0 056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗ AA/GSTP1∗IleIle carriers (p = 0 021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0 041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0 041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF. © 2019 Dejan Simeunovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Although the majority of previous findings unequivocally confirmed the existence of systemic oxidative stress in chronic heart failure (CHF) patients, data on prognostic potential of biomarkers of oxidative lipid and protein damage are limited. We aimed to address the relation of oxidative stress markers to severity and prognosis in CHF secondary to ischemic cardiomyopathy. Methods and Results: Plasma malondialdehyde (MDA), protein thiol groups (P-SH), reactive carbonyl derivatives (RCD), together with glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined in 120 CHF patients and 69 healthy controls. Increased lipid peroxidation (MDA) and oxidation of plasma proteins (RCD; P-SH) s well as downregulated GSH-Px activity were found in CHF patients compared with controls. Significant correlation was obtained only for RCD content and remodeling indices (LVEDV: r = 0.469, P =.008; LVESV: r = 0.452; P =.011). Cox regression analysis demonstrated only MDA (HR = 3.33; CI: 1.55-7.12; P =.002) as independent predictor of death, whereas SOD was associated with unstable angina pectoris (HR = 2.09; CI: 1.16-3.78; P =.011). Conclusions: In the course of CHF progression, carbonyl stress is implicated in the LV remodeling. Malondialdehyde level might be a useful parameter for monitoring and planning management of CHF patients. © 2012 Elsevier Inc. All rights reserved.

Background: We aimed to study the relationship between markers of oxidative lipid or protein damage and ventricular remodeling and the validity of 8-epi-prostaglandin F2α (8-epi-PGF2α) as an indicator of disease severity in patients with ischemic chronic heart failure (CHF). Patients and methods: We enrolled four groups of 12 patients with varying CHF according to the New York Heart Association (NYHA) classification and 25 controls. Urinary 8-epi-PGF2α and plasma malondialdehyde and protein thiol (P-SH) groups were correlated with echocardiographic indices of remodeling. The reliability of isoprostanes was analyzed by a receiver operating characteristics (ROC) curve. Results: NYHA class III and IV patients exhibited elevated 8-epi-PGF2α levels, increased malondialdehyde concentrations and decreased P-SH groups when compared to controls and NYHA I and II patients. 8-Epi-PGF2α and P-SH groups correlated significantly with indices of remodeling. The ROC curve drawn for 8-epi-PGF2α allowed us to differentiate NYHA class III and IV patients from NYHA class I and II patients with a sensitivity of 95.8% and specificity of 95.8% (cut off 0.84 ng/mg creatinine; area under curve 0.99; P < 0.001). Conclusions: Markers of oxidative damage are unlikely to play a significant role in early stages of CHF. However, they might become important in the course of CHF when their concentrations reach critical levels. Urinary 8-epi-PGF2α is a reliable indicator of symptomatic CHF. © 2008 W. S. Maney and Son Ltd.

Background: We aimed to study the relationship between markers of oxidative lipid or protein damage and ventricular remodeling and the validity of 8-epi-prostaglandin F2α (8-epi-PGF2α) as an indicator of disease severity in patients with ischemic chronic heart failure (CHF). Patients and methods: We enrolled four groups of 12 patients with varying CHF according to the New York Heart Association (NYHA) classification and 25 controls. Urinary 8-epi-PGF2α and plasma malondialdehyde and protein thiol (P-SH) groups were correlated with echocardiographic indices of remodeling. The reliability of isoprostanes was analyzed by a receiver operating characteristics (ROC) curve. Results: NYHA class III and IV patients exhibited elevated 8-epi-PGF2α levels, increased malondialdehyde concentrations and decreased P-SH groups when compared to controls and NYHA I and II patients. 8-Epi-PGF2α and P-SH groups correlated significantly with indices of remodeling. The ROC curve drawn for 8-epi-PGF2α allowed us to differentiate NYHA class III and IV patients from NYHA class I and II patients with a sensitivity of 95.8% and specificity of 95.8% (cut off 0.84 ng/mg creatinine; area under curve 0.99; P < 0.001). Conclusions: Markers of oxidative damage are unlikely to play a significant role in early stages of CHF. However, they might become important in the course of CHF when their concentrations reach critical levels. Urinary 8-epi-PGF2α is a reliable indicator of symptomatic CHF. © 2008 W. S. Maney and Son Ltd.

Objective Cardiovascular manifestations, encountered in antiphospholipid syndrome, may develop as a consequence of acquired thrombophilia mediated by antiphospholipid antibodies and accelerated atherosclerosis as well. Our study aims to assess the impairment of the left ventricular diastolic performance, as early evidence of myocardial involvement in primary antiphospholipid syndrome (PAPS). Methods We analysed 101 PAPS patients, with the average age of 47.70±13.14y. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. The results were compared to 90 healthy, age and sex-matched controls. Results LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). In PAPS patients, it was significantly related to age, body mass index, hyperlipidaemia, thromboses and LAC positivity (p=0.0001, p=0.008, p=0.039, p=0.001, p=0.047 respectively). Patients with PAPS had higher LAVI (29.76±6.40 ml/m2 vs. 26.62±7.8 ml/m2, p=0.012), higher isovolumic relaxation time, lower lateral É velocity and lower E/É ratio compared to controls (p=0.0001, p=0.020, p=0.038, respectively). In multivariate analysis, thromboses in PAPS were significant, and independent predictors of LVDD. Conclusion Thrombotic PAPS patients are at higher risk of LVDD development. Strong action against standard atherosclerotic risk factors and adequate therapy regimes seems to be crucial to preserve good diastolic performance of the left ventricle in PAPS. © Copyright CliniCal and ExpErimEntal rhEumatology 2023.

Objective Cardiovascular manifestations, encountered in antiphospholipid syndrome, may develop as a consequence of acquired thrombophilia mediated by antiphospholipid antibodies and accelerated atherosclerosis as well. Our study aims to assess the impairment of the left ventricular diastolic performance, as early evidence of myocardial involvement in primary antiphospholipid syndrome (PAPS). Methods We analysed 101 PAPS patients, with the average age of 47.70±13.14y. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. The results were compared to 90 healthy, age and sex-matched controls. Results LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). In PAPS patients, it was significantly related to age, body mass index, hyperlipidaemia, thromboses and LAC positivity (p=0.0001, p=0.008, p=0.039, p=0.001, p=0.047 respectively). Patients with PAPS had higher LAVI (29.76±6.40 ml/m2 vs. 26.62±7.8 ml/m2, p=0.012), higher isovolumic relaxation time, lower lateral É velocity and lower E/É ratio compared to controls (p=0.0001, p=0.020, p=0.038, respectively). In multivariate analysis, thromboses in PAPS were significant, and independent predictors of LVDD. Conclusion Thrombotic PAPS patients are at higher risk of LVDD development. Strong action against standard atherosclerotic risk factors and adequate therapy regimes seems to be crucial to preserve good diastolic performance of the left ventricle in PAPS. © Copyright CliniCal and ExpErimEntal rhEumatology 2023.

Aims: Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline-recommended therapy in Europe and other ESC affiliated countries. Methods: Between 1 November 2018 and 31 December 2020, 10 162 patients with chronic or acute/worsening HF with reduced, mildly reduced, or preserved ejection fraction were enrolled from 220 centres in 41 European or ESC affiliated countries. The ESC HF III Registry collected data on baseline characteristics (hospital or clinic presentation), hospital course, diagnostic and therapeutic decisions in hospital and at the clinic visit; and on outcomes at 12-month follow-up. These data include demographics, medical history, physical examination, biomarkers and imaging, quality of life, treatments, and interventions – including drug doses and reasons for non-use, and cause-specific outcomes. Conclusion: The ESC HF III Registry will provide comprehensive and unique insight into contemporary HF characteristics, treatment implementation, and outcomes, and may impact implementation strategies, clinical discovery, trial design, and public policy. © 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Introduction and objectives Uric acid and gamma-glutamyl transferase are prognostic indicators in chronic heart failure. Nevertheless, the mechanism underlying the association between uric acid, gamma-glutamyl transferase, and chronic heart failure progression and prognosis remains largely unknown. Methods The association of uric acid and gamma-glutamyl transferase with flow-mediated dilation and echocardiographic indices of cardiac remodeling was addressed in 120 patients with chronic ischemic heart failure. To determine the independent contribution of uric acid and gamma-glutamyl transferase to the flow-mediated dilation and echocardiographic indices of remodeling, a series of multiple linear regression models, based on traditional and nontraditional risk factors impacting upon these parameters, were constructed. Results Uric acid, but not gamma-glutamyl transferase, was an independent predictor of flow-mediated dilation. Uric acid was associated with all the echocardiographic indices of left ventricular dysfunction tested in 3 multiple-regression models. Uric acid correlated with left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular end-systolic volume, and left ventricular end-diastolic volume (r = 0.337; r = 0.340; r = 0.321; r = 0.294; P =.001, respectively). Gamma-glutamyl transferase was an independent predictor of left ventricular end-systolic volume and left ventricular end-diastolic volume, after adjustment for all variables. Gamma-glutamyl transferase correlated with left ventricular end-diastolic diameter, left ventricular end-diastolic diameter, left ventricular end-systolic volume, and left ventricular end-diastolic volume (r = 0.238, P =.009; r = 0.219, P =.016; r = 0.359, P <.001; r = 0.369, P =.001, respectively). Conclusions Serum uric acid and gamma-glutamyl transferase levels are associated with left ventricular remodeling in patients with chronic ischemic heart failure. Full English text available from: www.revespcardiol.org/en. © 2013 Sociedad Española de Cardiología. Published by Elsevier España, S.L. All rights reserved.