The Role of Oxidative Stress and Inflammatory Parameters in Heart Failure.

Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide (BNP), in a simple blood test are the gold-standard biomarkers for HF diagnosis. However, even good biomarkers such as natriuretic peptides fail to predict all the risks associated with HF due to the diversity of the mechanisms involved. The pathophysiology of HF is determined by numerous factors, including oxidative stress, inflammation, neuroendocrine activation, pathological angiogenesis, changes in apoptotic pathways, fibrosis and vascular remodeling. High readmission and mortality rates prompt a search for new markers for the diagnosis, prognosis and treatment of HF. Oxidative-stress-mediated inflammation plays a crucial role in the development of subsequent changes in the failing heart and provides a new insight into this complex mechanism. Oxidative stress and inflammatory biomarkers appear to be a promising diagnostic and prognostic tool in patients with HF. This systematic review provides an overview of the current knowledge about oxidative stress and inflammation parameters as markers of HF.

Association of NT-proBNP and sST2 with Left Ventricular Ejection Fraction and Oxidative Stress in Patients with Stable Dilated Cardiomyopathy.

The aim of this study was to analyze the relationship between levels of sST2, NT-proBNP and oxidative stress markers in patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy. A total of 88 patients with HFrEF were divided into four groups based on left ventricular ejection fraction (≤25% and >25%) and NYHA functional class (group 1-LVEF > 25% and NYHA class I or II; group 2-LVEF > 25% and NYHA class III or IV; group III-LVEF ≤ 25% and NYHA class I or II; group IV-LVEF ≤ 25% and NYHA class III or IV). In 39 (44.32%) patients LVEF was reduced below 25%, and 22 of them (56.41%) were in NYHA functional class III/IV. Of the 49 (55.68%) patients with LVEF ≥ 25%, only 18.37% were in NYHA functional class III/IV (p < 0.001). Patients with LVEF ≥ 25% had lower levels of NT-proBNP, total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI). The levels of NT-proBNP but not sST-2 correlated positively with NYHA functional class (p < 0.001) and negatively with LVEF (p < 0.001). The levels of sST-2 were associated with increased TAC (p = 0.009) and uric acid (p = 0.040). These findings indicate that only NT-proBNP was related to the severity of heart failure, whereas sST2 correlated with total antioxidant capacity. Therefore, in stable patients with HFrEF due to dilated cardiomyopathy, sST2 may be an additional biomarker reflecting the redox status, but not the severity of heart failure.

The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress-Role of New Drugs, Flozins.

Heart failure (HF) is a multifactorial clinical syndrome involving many complex processes. The causes may be related to abnormal heart structure and/or function. Changes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the natriuretic peptide system are important in the pathophysiology of HF. Dysregulation or overexpression of these processes leads to changes in cardiac preload and afterload, changes in the vascular system, peripheral vascular dysfunction and remodeling, and endothelial dysfunction. One of the important factors responsible for the development of heart failure at the cellular level is oxidative stress. This condition leads to deleterious cellular effects as increased levels of free radicals gradually disrupt the state of equilibrium, and, as a consequence, the internal antioxidant defense system is damaged. This review focuses on pharmacotherapy for chronic heart failure with regard to oxidation-reduction metabolism, with special attention paid to the latest group of drugs, SGLT2 inhibitors-an integral part of HF treatment. These drugs have been shown to have beneficial effects by protecting the antioxidant system at the cellular level.

Pregnancy in Patients with Pulmonary Arterial Hypertension in Light of New ESC Guidelines on Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is defined as an elevated mean pulmonary artery pressure (mPAP) of >20 mmHg together with a pulmonary arterial wedge pressure (PAWP) of ≤15 mmHg and pulmonary vascular resistance (PVR) of>2 Wood units (WU). Although the total mortality of pregnant women with PAH has decreased significantly in recent years and is reported to be around 12% in some databases, total mortality is still at an unacceptably high percentage. Moreover, some subgroups, such as patients with Eisenmenger's syndrome, have a particularly high mortality rate of up to 36%. Pregnancy in patients with PAH is contraindicated; its appearance is an indication for a planned termination. Education of patients with PAH, including counseling on effective contraception, is essential. During pregnancy, blood volume, heart rate, and cardiac output increase, while PVR and systemic vascular resistance decrease. The hemostatic balance is shifted towards hypercoagulability. Among PAH-specific drugs, the use of inhaled or intravenous prostacyclins, phosphodiesterase inhibitors, and calcium channel blockers (in patients with preserved vasoreactivity) is acceptable. Endothelin receptor antagonists and riociguat are contraindicated. Childbirth can take place through either vaginal delivery or caesarean section; similarly, neuraxial and general anesthesia have proven indications. In a situation where all pharmacological options have been used in pregnant or postpartum patients in a serious condition, veno-arterial ECMO is a useful therapeutic option. For PAH patients who want to become mothers, an option that does not endanger their lives is adoption.

Levels of TNF-α and Soluble TNF Receptors in Normal-Weight, Overweight and Obese Patients with Dilated Non-Ischemic Cardiomyopathy: Does Anti-TNF Therapy Still Have Potential to Be Used in Heart Failure Depending on BMI?

Background. We sought to measure the levels of adipokines, TNF-α and soluble receptors (sTNFr1, sTNFr2) in heart failure patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy (nDCM). Methods. A total of 123 patients with HFrEF due to nDCM were divided into three groups according to BMI: 34 (27.6%) normal weight, 56 (45.5%) overweight and 33 (26.8%) obese. A six-minute walk test, echocardiography and right heart catheterization were performed. Serum concentrations of adiponectin, leptin, NT-proBNP, blood hemoglobin, sodium, creatinine, ALAT, AspAT, bilirubin, CRP, lipids, TNF-α, sTNFr1 and sTNFr2 receptors were measured. Results. Obese patients had the lowest NT-proBNP concentrations, significantly higher leptin levels and higher leptin/adiponectin ratios. The concentration of sTNFr1 was higher in normal-weight patients. In all groups, TNF-α concentrations correlated positively with sTNFr1 (p < 0.001). Higher levels of sTNFr1 were associated with higher sTNFr2 (p < 0.001) and CRP (p < 0.001). Moreover, the concentration of sTNFr2 positively correlated with CRP (p < 0.05) and adiponectin (p < 0.001). Levels of TNF-α were not associated with elevated CRP. Conclusion: This study demonstrated that changes in the concentrations of TNF and its receptors differ between groups of patients with different BMI. These findings suggest that the effective use of anti-TNF therapy is dependent not only on BMI, but also on concentrations of TNF-α receptors and other laboratory parameters.

Pathomechanisms of SARS-CoV-2 infection and development of atherosclerosis in patients with COVID-19: A review.

The pandemic of coronavirus disease 2019 (COVID-19) has posed a major health challenge for over 2 years. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes it belongs to single-stranded ribonucleic acid viruses and causes acute respiratory distress syndrome. The initial outbreak was discovered in December 2019 in Wuhan province, where SARS-CoV-2 quickly spread to other countries. In addition to respiratory disorders, it has been shown that during and after COVID-19 infection, cardiovascular diseases are often developed or exacerbated, such as: arterial hypertension, coronary artery disease, arrhythmias, heart failure and thromboembolic complications. In view of the higher prevalence of atherosclerosis in patients with COVID-19, we described the pathomechanisms of the development of this infection and the possible correlations between SARS-CoV-2 infection and thromboembolic complications. We focused on the role of the inflammatory response, renin-angiotensin system and endothelial dysfunction in the development of atherosclerosis in patients with COVID-19. A thorough understanding of the hemodynamic mechanisms and the impact of the infection on the cardiovascular system will allow for the proper selection of appropriate therapy in patients after SARS-CoV-2 infection.

Ceruloplasmin as Redox Marker Related to Heart Failure Severity.

This study examined ceruloplasmin levels in patients with HFrEF, depending on cardiopulmonary exercise testing (CPET) parameters; a correlation was found between ceruloplasmin (CER) and iron and hepatic status, inflammatory and redox biomarkers. A group of 552 patients was divided according to Weber's classification: there were 72 (13%) patients in class A (peak VO2 > 20 mL/kg/min), 116 (21%) patients in class B (peak VO2 16-20 mL/kg/min), 276 (50%) patients in class C (peak VO2 10-15.9 mL/kg/min) and 88 (16%) patients in class D (peak VO2 < 10 mL/kg/min). A higher concentration of CER was found in patients with peak VO2 < 16 mL/kg/min and VE/CO2 slope > 45 compared to patients with VE/CO2 slope < 45 (escectively CER 30.6 mg/dL and 27.5 mg/dL). A significantly positive correlation was found between ceruloplasmin and NYHA class, RV diameter, NT-proBNP, uric acid, total protein, fibrinogen and hepatic enzymes. CER was positively correlated with both total oxidant status (TOS), total antioxidant capacity (TAC) and malondialdehyde. A model constructed to predict CER concentration indicated that TOS, malondialdehyde and alkaline phosphatase were independent predictive variables (R2 0.14, p < 0.001). CER as a continuous variable was an independent predictor of pVO2 ≤ 12 mL/kg/min after adjustment for sex, age and BMI. These results provide the basis of a new classification to encourage the determination of CER as a useful biomarker in HFrEF.

Serum Sulfhydryl Groups, Malondialdehyde, Uric Acid, and Bilirubin as Predictors of Adverse Outcome in Heart Failure Patients due to Ischemic or Nonischemic Cardiomyopathy.

Oxidative stress plays a significant role in the pathogenesis of heart failure (HF). The aim of the study was to investigate the prognostic value of oxidation-reduction (redox) markers in patients with HF due to ischemic and nonischemic cardiomyopathy. The study included 707 patients of HF allocated into two groups depending on ethology: ischemic cardiomyopathy (ICM) (n = 435) and nonischemic cardiomyopathy (nICM) (n = 272), who were followed up for one year. The endpoint occurrence (mortality or heart transplantation) in a 1-year follow-up was similar in the ICM and nICM group. The predictive value of endpoint occurrence of oxidative stress biomarkers such as the serum protein sulfhydryl groups (PSH), malondialdehyde (MDA), uric acid (UA), bilirubin, and MDA/PSH ratio and other clinical and laboratory data were assessed in both groups (ICM and nICM) separately using univariate and multivariate Cox regression analyses. In multivariate analysis, the higher concentrations of UA (p = 0.015, HR = 1.024, 95% CI (1.005-1.044)) and MDA (p = 0.004, HR = 2.202, 95% CI (1.296-3.741)) were significantly associated with adverse prognosis in patients with ICM. Contrastingly, in patients with nICM, we observed that higher bilirubin concentration (p = 0.026, HR = 1.034, 95% CI (1.004-1.064)) and MDA/PSH ratio (p = 0.034, HR = 3.360, 95% CI (1.096-10.302)) were significantly associated with increased risk of death or HT. The results showed the association of different oxidative biomarkers on the unfavorable course of heart failure depending on etiology.

Decreased immunoreactivity of von Willebrand factor may reflect persistent nature of the endothelial dysfunction in non-ischemic heart failure.

INTRODUCTION: Endothelial dysfunction is a critical part of heart failure (HF) pathophysiology. It is not clear, however, whether it is present at the similar level in the early and late HF stages. MATERIAL AND METHODS: von Willebrand factor (vWF) and its mRNA levels in biopsies of non-ischemic patients with HF secondary to dilated cardiomyopathy were studied. Consecutive patients with HF were divided into two groups: group A with disease duration ≤ 12 months (n = 59) and group B with disease duration > 12 months (n = 68). The immunoreactivity of the vWF was compared with autopsy sections of 19 control cases. Tissue vWF gene expression was analyzed at the mRNA level by RT-PCR. RESULTS: In the group A, there was lower vWF immunoreactivity in the coronary microvessels compared to the group B [1.5 (1.0-2.0) vs. 2.0 (1.5-2.4), P = 0.001]. In the control group, only weak vWF expression was observed. Protein expression was not accompanied by vWF mRNA whose levels were significantly higher in the Group A as compared to the Group B [14671 (4932-51561) vs. 3643 (185.3-9030.8), P = 0.005]. Protein vWF expression was inversely associated with its mRNA levels (r = -0.34, P = 0.04). CONCLUSIONS: High myocardial protein expression of vWF in patients with long-lasting HF symptoms may highlight the persistent nature of endothelial dysfunction in such a cohort of patients.

DIAGNOSTIC AND PREDICTIVE VALUE OF RIGHT HEART CATHETERIZATION-DERIVED MEASUREMENTS IN PULMONARY HYPERTENSION.

Right heart catheterization is a unique tool not only in the diagnosis but also in the management of patients with a wide range of cardiovascular diseases. The technique dates back to the 18th century, but the biggest advances were made in the 20th century. This review focuses on pulmonary hypertension for which right heart catheterization remains the diagnostic gold standard. Right heart catheterization-derived parameters help classify pulmonary hypertension into several subgroups, assess risk of adverse events or mortality and make therapeutic decisions. According to the European Society of Cardiology guidelines pulmonary hypertension (PH) is defined as an increase in mean pulmonary artery pressure (PAPm) > 25 mmHg, whereas a distinction between pre- and post-capillary PH is made based on levels of pulmonary artery wedge pressure (PAWP). Moreover, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) are the only parameters recommended to assess prognosis and only in patients with pulmonary arterial hypertension (PAH). Patients with RAP > 14 mmHg, CI < 2.0 l/min/m2 and SvO2 < 60% are at high (> 10%) risk of death within the next year. The purpose of this paper is to show that RHC-derived parameters can be used on a considerably larger scale than currently recommended. Several prognostic parameters, with specific thresholds have been identified for each subtype of pulmonary hypertension and can be helpful in everyday practice for treatment of PH.

Nitric Oxide Stroke Volume Index as a New Hemodynamic Prognostic Parameter for Patients with Pulmonary Arterial Hypertension.

The aim of the study was to determine the prognostic value of hemodynamic parameters measured during initial diagnostic right heart catheterization (RHC) in standard conditions and using a nitric oxide reversibility test. A retrospective observational study of 62 patients with pulmonary arterial hypertension (PAH) was performed. Clinical, biochemical, echocardiographic, and hemodynamic data obtained at the time of the PAH diagnosis were precisely analyzed. Patients were followed for five years. Death or lung transplantation was considered as a primary endpoint. The mean follow-up period was 1090 ± 703 days and the median age was 46.84 years. In the studied group, 25 patients survived, 36 patients died, and one underwent a lung transplantation. From all the examined parameters, only stroke volume index during reversibility test with iNO (SVI(NO test)) (HR = 0.910; 95% confidence interval 0.878-0.944; p < 0.001) and initial arterial oxygen saturation (SaO2) (HR = 0.910; 95% confidence interval 0.843-0.982; p = 0.015) have been established as independent predictors of death or lung transplantation in the five-year follow-up. An SVI(NO test) value above 39.86 mL/m2 was associated with 100% five-year survival rate (AUC = 0.956; 95% confidence interval 0.899-1.000; p < 0.001; specificity/sensitivity: 100/84%). The results of the analysis suggest that the SVI(NO test) measured during the initial diagnostic RHC could be a very valuable prognostic factor in the PAH patients.

Ceruloplasmin, NT-proBNP, and Clinical Data as Risk Factors of Death or Heart Transplantation in a 1-Year Follow-Up of Heart Failure Patients.

We investigated whether the additional determination of ceruloplasmin (Cp) levels could improve the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients in a 1-year follow-up. Cp and NT-proBNP levels and clinical and laboratory parameters were assessed simultaneously at baseline in 741 HF patients considered as possible heart transplant recipients. The primary endpoint (EP) was a composite of all-cause death (non-transplant patients) or heart transplantation during one year of follow-up. Using a cut-off value of 35.9 mg/dL for Cp and 3155 pg/mL for NT-proBNP (top interquartile range), a univariate Cox regression analysis showed that Cp (hazard ratio (HR) = 2.086; 95% confidence interval (95% CI, 1.462-2.975)), NT-proBNP (HR = 3.221; 95% CI (2.277-4.556)), and the top quartile of both Cp and NT-proBNP (HR = 4.253; 95% CI (2.795-6.471)) were all risk factors of the primary EP. The prognostic value of these biomarkers was demonstrated in a multivariate Cox regression model using the top Cp and NT-proBNP concentration quartiles combined (HR = 2.120; 95% CI (1.233-3.646)). Lower left ventricular ejection fraction, VO2 max, lack of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, and nonimplantation of an implantable cardioverter-defibrillator were also independent risk factors of a poor outcome. The combined evaluation of Cp and NT-proBNP had advantages over separate NT-proBNP and Cp assessment in selecting a group with a high 1-year risk. Thus multi-biomarker assessment can improve risk stratification in HF patients.

Malondialdehyde and Uric Acid as Predictors of Adverse Outcome in Patients with Chronic Heart Failure.

In chronic heart failure (HF), some parameters of oxidative stress are correlated with disease severity. The aim of this study was to evaluate the importance of oxidative stress biomarkers in prognostic risk stratification (death and combined endpoint: heart transplantation or death). In 774 patients, aged 48-59 years, with chronic HF with reduced ejection fraction (median: 24.0 (20-29)%), parameters such as total antioxidant capacity, total oxidant status, oxidative stress index, and concentration of uric acid (UA), bilirubin, protein sulfhydryl groups (PSH), and malondialdehyde (MDA) were measured. The parameters were assessed as predictive biomarkers of mortality and combined endpoint in a 1-year follow-up. The multivariate Cox regression analysis was adjusted for other important clinical and laboratory prognostic markers. Among all the oxidative stress markers examined in multivariate analysis, only MDA and UA were found to be independent predictors of death and combined endpoint. Higher serum MDA concentration increased the risk of death by 103.0% (HR = 2.103; 95% CI (1.330-3.325)) and of combined endpoint occurrence by 100% (HR = 2.000; 95% CI (1.366-2.928)) per µmol/L. Baseline levels of MDA in the 4th quartile were associated with an increased risk of death with a relative risk (RR) of 3.64 (95% CI (1.917 to 6.926), p < 0.001) and RR of 2.71 (95% CI (1.551 to 4.739), p < 0.001) for the occurrence of combined endpoint as compared to levels of MDA in the 1st quartile. Higher serum UA concentration increased the risk of death by 2.1% (HR = 1.021; 95% CI (1.005-1.038), p < 0.001) and increased combined endpoint occurrence by 1.4% (HR = 1.014; 95% CI (1.005-1.028), p < 0.001), for every 10 µmol/L. Baseline levels of UA in the 4th quartile were associated with an increased risk for death with a RR of 3.21 (95% CI (1.734 to 5.931)) and RR of 2.73 (95% CI (1.560 to 4.766)) for the occurrence of combined endpoint as compared to the levels of UA in the 1st quartile. In patients with chronic HF, increased MDA and UA concentrations were independently related to poor prognosis in a 1-year follow-up.

Comparison of Oxidative Stress Parameters in Heart Failure Patients Depending on Ischaemic or Nonischaemic Aetiology.

BACKGROUND: Abnormalities in the oxidative and antioxidant states causing oxidative stress were both found in heart failure (HF) of various aetiologies and atherosclerosis. AIM OF STUDY: The goals of the study were as follows: comparison of oxidative stress parameters (OSP) in ischaemic cardiomyopathy (ICM) (n = 479) and nonischaemic cardiomyopathy (nICM) (n = 295) patients; assessment of the relationships of OSP with functional capacity (NYHA class), maximal oxygen consumption (max.O2), left ventricle ejection fraction (LVEF), and NT-proBNP concentration; and determination of the mutual relations of OSP in subgroups of patients with ICM and n-ICM. METHODS: Serum concentrations of total antioxidant capacity (TAC), total oxidant status (TOS), uric acid (UA), bilirubin, albumin, protein sulfhydryl groups (PSH), and malondialdehyde (MDA) were measured. The oxidative stress index (OSI) and MDA/PSH ratio were calculated. RESULTS: Higher concentrations of TAC (1.14 vs 1.11 mmol/l; p < 0.001) and MDA (1.80 vs 1.70 µmol/l; p < 0.05) and higher MDA/PSH ratios (0.435 vs 0.358; p < 0,001) were observed in ICM than in nICM patients. Simultaneously, lower values of the OSI index (4.27 vs 4.6; p < 0, 05), PSH (4.10 vs 4.75 µmol/g of protein; p < 0,001), and bilirubin (12.70 vs 15.40 µmol/l; p < 0,001) concentrations were indicated in ICM patients. There were no differences in TOS, UA, and albumin between the examined groups. The NYHA class and VO2max correlate with MDA, bilirubin, and albumin in both groups, while with UA only in the ICM group. Correlations between the NYHA class, VO2max, and PSH were indicated in nICM. The association of LVEF with UA, bilirubin, and albumin has been demonstrated in the ICM group. The study showed negative correlations between TAC, MDA, and PSH and positive between TAC and MDA in both groups. In ICM patients, MDA positively correlated with UA. A negative correlation between PSH and concentrations of UA and bilirubin was expressed only in the nICM group. CONCLUSION: The obtained results confirm the relationship between the severity of HF and oxidative stress. The mechanisms of oxidative stress and antioxidant defence are partially different in the ICM and the nICM patients.

Correction to: Superoxide dismutase activity as a predictor of adverse outcomes in patients with nonischemic dilated cardiomyopathy.

Due to an unfortunate turn of events, part of the data in the columns HR, 95% CI and p is missing from Figs. 4-9 of the original publication.

Superoxide dismutase activity as a predictor of adverse outcomes in patients with nonischemic dilated cardiomyopathy.

Oxidative stress contributes to progression of heart failure (HF). The present study analyzed the efficacy of the activities of superoxide dismutase (SOD) and its isoenzymes (CuZnSOD and MnSOD) as prognostic factors in dilated cardiomyopathy. The usefulness of activities of total SOD, MnSOD, and CuZnSOD was assessed, taking into account clinical, echocardiographic, and laboratory parameters as risk predictors of long-term clinical outcomes (death, heart transplant, combined end point) in 109 patients with nonischemic dilated cardiomyopathy (NIDCM) in this study with a 5-year follow-up. Regression analysis showed that total serum SOD activity was a predictor of worse long-term clinical outcome even after adjustment for NT-proBNP, hemoglobin, sodium, creatinine clearance, left ventricular ejection fraction (LVEF), BMI, and NYHA class (LVEF: HR 1.059, 95% CI 1.007-1.114, P = 0.026; BMI: HR 1.073, 95% CI 1.021-1.126, P = 0.005; NYHA: HR 1.073, 95% CI 1.022-1.126, P = 0.005). MnSOD and CuZnSOD activities were also predictors of worse long-term clinical outcome even after adjustment for laboratory parameters and BMI or NYHA class; however, after adjustment for LVEF, a borderline statistical significance was achieved (LVEF: HR 1.054, 95% CI 0.993-1.119, P = 0.081 [MnSOD]; HR 1.092, 95% CI 0.989-1.297, P = 0.082 [CuZnSOD]). Increased activities of total serum SOD and its isoenzymes in NIDCM patients correspond with a poor prognosis and may have prognostic value in the prediction of long-term clinical outcomes. In conclusion, the present study shows that serum SOD activity may be a useful predictor of adverse outcome in HF.

The concentration of interleukin-33 in heart failure with reduced ejection fraction.

OBJECTIVE: Despite several improvements in the management of heart failure (HF), it is still an incurable and a progressive disease. Several trials demonstrated that the process of inflammation may be responsible for initiation and progression of HF. The aim of the present study was to investigate the role of interleukin-33 (IL-33) in the pathogenesis of HF and to assess whether disease etiology and course of the disease affect the expression of cytokines. METHODS: The study included 155 (106 male and 49 female) patients with systolic HF with a mean left ventricle ejection fraction of 32.13+-12.8% and 60 (36 male and 24 female) healthy individuals. IL-33 concentrations were evaluated using enzyme-linked immunosorbent assay. RESULTS: The concentration of IL-33 was statistically significantly lower in patients with HF than in healthy subjects, 16.91 (0-81.00) pg/mL and 92.51 (33.61-439.61) pg/mL, respectively. Patients with HF with ischemic etiology had lower concentration of IL-33 (10.75 pg/mL) than subjects with HF with non-ischemic etiology (21.05 pg/mL). Patients with stable HF (10.46 pg/mL) had lower IL-33 levels than those with unstable HF (19.02 pg/mL). CONCLUSION: The concentrations of IL-33 were lower in patients with HF than in healthy controls, which may play an important role of above cytokine in HF development and progression. In addition, interleukin concentrations varied depending on the etiology and severity of the course of the disease.

The multiple systemic artery to pulmonary artery fistulas resulting in severe irreversible pulmonary arterial hypertension in patient with previous history of pneumothorax.

BACKGROUND: Systemic artery to pulmonary artery fistulas (SA-PAFs), are extremely rare in people without congenital heart disease. In this group of patients pulmonary arterial hypertension was reported in the single case. Then, we describe a case of multiple SA-PAFs, which were the cause of severe nonreversible arterial pulmonary hypertension in a patient who had a right-sided pneumothorax 35 years earlier. CASE PRESENTATION: 52-year-old male Caucasian patient with echocardiographically confirmed pulmonary hypertension (PH) was admitted to cardiology department due to exertional dyspnea and signs of right ventricle failure. Routine screening for causes of secondary PH was negative. Right heart catheterization (RHC) confirmed a high degree arterial PH [mean pulmonary artery pressure (mPAP); 50,6 mmHg, pulmonary wedge pressure (PWP); 11,3 mmHg, pulmonary vascular resistance (PVR); 11,9 Wood's units (WU)] irreversible in the test with inhaled nitric oxide. Oxygen saturation (SaO2) of blood samples obtained during the first RHC ranged from 69.3 to 73.2%. Idiopathic pulmonary arterial hypertension was diagnosed. Treatment with inhaled iloprost and sildenafil was initiated. Control RHC, performed 5 months later showed values of mPAP (59,7 mmHg) and PVR (13,4 WU) higher in comparison to the initial measurement, SaO2 of blood obtained during RHC from upper lobe artery of the right lung was elevated and amounted 89.7%. Then, pulmonary arteriography was performed. Lack of contrast in the right upper lobe artery with the evidence of retrograde blood flow visible as a negative contrast in the right pulmonary artery was found. Afterwards, right subclavian artery arteriography detected a huge vascular malformation communicating with right upper lobe artery. Following computed tomography angiogram (angio-CT) additionally revealed the enlargement of bronchial arteries originated fistulas to pulmonary artery of right upper lobe. In spite of intensive pharmacological treatment, including the therapy of pulmonary hypertension and percutaneous embolisation of the fistulas, the patient's condition continued to deteriorate further. He died three months after embolisation due to severe heart failure complicated by pneumonia. CONCLUSION: Non-congenital SA-PAFs are extremely rare, however, they should be excluded in patients with pulmonary arterial hypertension and history of inflammatory or infectious disease of the lung and pleura, pneumothorax, cancer or Takayashu's disease and after chest trauma.

Ten-year study of late electrotherapy complications. Single-centre analysis of indications and safety of transvenous leads extraction.

BACKGROUND: An increase in the number of cardiac implantable electronic device (CIED) implantations is associated with a higher frequency of electrotherapy complications. AIM: The aim of the study was to determine the risk factors for late electrotherapy complications and to evaluate the effectiveness of transvenous lead extraction (TLE) and survival after TLE. METHODS: We analysed the clinical data of 225 patients with electrotherapy complications referred for TLE in a single centre in the years 2006 to 2015. Indications for TLE, risk factors for infectious complications, effectiveness of TLE, and survival after the procedure were assessed. RESULTS: In the study group, non-infectious indications for TLE predominated (78.2%). Analysis of risk for infectious complications demonstrated the important role of chronic renal failure (hazard ratio [HR] 1.842, p = 0.034) and a greater number of CIED-related procedures (HR 4.768, p < 0.001). High effectiveness of TLE and significantly higher long-term mortality of patients with infectious complications compared with the remainder (50% vs. 20%, p < 0.05) were documented. CONCLUSIONS: The study demonstrated a high rate of patients with non-infectious complications referred for TLE and very high effectiveness of the procedure. The worse long-term survival of patients with infectious complications, as well as increased risk for such complications due to the greater number of prior procedures, should prompt the consideration of early referral for TLE in the case of lead dysfunctions.