Bożena Sobkowicz

Fibrinolysis for patients with intermediate-risk pulmonary embolism

BACKGROUND The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial. METHODS In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization. RESULTS Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42). CONCLUSIONS In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

Apelin: a novel marker for the patients with first ST-elevation myocardial infarction

To date, only animal studies have been concerned with apelin involvement in acute myocardial ischemia. The aim of this study was to investigate apelin measurements in low-risk patients with first ST-elevation myocardial infarction (STEMI) and to assess if apelin may feature as a marker of left ventricular (LV) injury and prognosis. In 78 consecutive patients (mean age 67 ± 11.5 years, 24 women) with first STEMI treated with primary percutaneous coronary intervention, plasma apelin-36 concentrations were measured twice: on admission and on the 5th day of hospitalization. Left ventricle ejection fraction (LVEF) was applied as marker of LV injury. Composite endpoint (CEP), which included death, stroke, and recurrent ischemic event, was assessed after 1 year follow-up. On the first day, median apelin-36 concentration was 2138.5 pg/ml and on the 5th day was significantly lower, 2008.3 pg/ml (P = 0.002). There were no significant differences found in apelin-36 concentrations between patients with normal and low LVEF. In both groups significant reductions were found in apelin-36 concentrations measured in 5-day intervals (P = 0.04 and P = 0.008, respectively). After a 1-year follow-up, only one patient died and 19 patients (24.3%) had reached CEP. No difference in baseline apelin-36 concentrations were found in the group of patients who reached CEP compared with those without CEP. However, in both groups concentrations significantly decreased after 5 days (P = 0.04 and P = 0.013, respectively). Apelin-36 concentrations are reduced in lowrisk first STEMI patients during the first days regardless of the degree of LV dysfunction and prognosis.

Apelin in acute myocardial infarction and heart failure induced by ischemia.

Apelin is a recently isolated novel endogenous ligand for the angiotensin-like 1 receptor (APJ). Initial experiments in animal models indicate that the cardiovascular system is the main target of the apelin-APJ system. Apelin plays an opposite role to the renin-angiotensin-aldosterone system as a compensatory mechanism. It is reduced in patients with heart failure, also of ischemic origin. However, only animal studies concern the role of the apelin-APJ system in myocardial ischemia. Less is known about the function of this adipokine in an acute phase of myocardial infarction in human. The apelin-APJ system could perhaps be involved in myocardial protection during acute myocardial ischemia. In the current review we have summarized recent data concerning the role of apelin in acute myocardial infarction and heart failure induced by ischemia.

The value of apelin-36 and brain natriuretic peptide measurements in patients with first ST-elevation myocardial infarction☆

BACKGROUND We aimed to assess apelin-novel endogenous ligand for the angiotensin-like 1 receptor in patients with ST-elevation myocardial infarction (STEMI) and to compare its value with B-type natriuretic peptide (BNP). METHODS In 78 consecutive patients with first STEMI treated with primary PCI, plasma apelin-36 (RIA) and BNP (MEIA) concentrations were measured twice: on admission and on the fifth day of hospitalization. Left ventricle ejection fraction (LVEF) was assessed on admission and composite endpoint (CEP)-after 1 year follow-up. RESULTS During the 5-day interval median plasma BNP level significantly increased and median plasma apelin concentration significantly decreased. BNP, but not apelin, correlated with low LVEF (<50%). In ROC analysis only BNP measurements were diagnostic for low LVEF. In ANOVA test, in patients with CEP, a significant decrease in apelin (but not BNP) concentrations measured in 5-day interval was found. ROC analysis identified only second BNP measurement as significant to estimate adverse outcome 0.627 in the prediction of CEP (95% confidence interval=0.507-0.736). CONCLUSION Following STEMI there is a decrease of plasma apelin-36 concentration and an increase of plasma BNP concentration. BNP is better, than apelin diagnostic value for the detection of impaired LVEF. Both BNP and apelin have prognostic value, although both needs further evaluation.

Serum levels of CD163 and TWEAK in patients with pulmonary arterial hypertension

BACKGROUND Inflammation may play a pivotal role in the pathogenesis of pulmonary arterial hypertension (PAH). We evaluated the concentrations of serum sTWEAK, its scavenger receptor sCD163 and sTWEAK/sCD163 ratio in patients with PAH. DESIGN The study enrolled 26 stable patients with PAH confirmed by right heart catheterization and 24 healthy volunteers matched for age, sex and body weight. All patients underwent transthoracic echocardiography, cardiopulmonary exercise test, 6-min walk test, measurement of lung diffusing capacity for the carbon monoxide (DLCO) and venous blood tests. Concentrations of sTWEAK and sCD163 were determined using ELISA kits. RESULTS The PAH patients were characterized by significantly higher median serum sCD163 levels (1072 vs 890ng/ml, p=0.04) together with lower serum sTWEAK concentrations (200 vs 278.1pg/ml, p=0.003) comparing to control subjects. sTWEAK/sCD163 ratio was therefore significantly lower in PAH group (0.18 vs 0.33, p=0.0005). No correlation was found between sTWEAK and sCD163 concentrations in both groups. We observed statistically significant inverse correlation between peak VO2 consumption and sCD163 concentrations (r=-0.52, p<0.05) and positive with sTWEAK/sCD163 ratio (r=0.45, p<0.05) in PAH group. Moreover, sTWEAK/sCD163 ratio positively correlated with % of predicted values of DLCO (r=0.42, p<0.05). CONCLUSIONS Patients with PAH present altered serum sTWEAK and sCD163 levels. The sTWEAK/sCD163 ratio appears to be a better indicator of the severity of PAH as compared to sTWEAK or sCD163 alone. The exact role of sCD163 or interaction between CD163 and sTWEAK in the initiation or progression of PAH as well as their potential prognostic significance remains to be established.

Hypotensive effect of atorvastatin in hypertensive patients: the association among flow-mediated dilation, oxidative stress and endothelial dysfunction

Introduction To investigate the hypothesis that atorvastatin decreases blood pressure (BP) values and improves endothelial function assessed by flow-mediated dilation (FMD) in normolipidaemic hypertensive patients. Material and methods Fifty-six hypertensive patients were randomized in a 2 : 1 proportion to atorvastatin (80 mg/day/3 months; group A; n = 39) or previous standard anti-hypertensive therapy (group B), which means the patients were treated with angiotensin-converting enzyme inhibitors, diuretics, β-blockers, calcium antagonists and angiotensin receptor blockers. The study had a crossover design: after 3 months, both groups were changed (group A* stopped and group B* started atorvastatin treatment). Nitric oxide (NO), total antioxidant status (TAS), endothelin-1 (ET-1), and peroxide concentrations as well as FMD were measured before, after 3 and after 6 months of treatment. Atorvastatin added to existing treatment decreased BP in both groups. Results Flow-mediated dilation improved in both statin-treated groups, but only significantly in group B* (from 11.9 ±8.3% to 22.1 ±9.0%; p < 0.05). In patients with FMD improvement, there was a greater BP reduction. After treatment discontinuation, FMD significantly decreased (from 19.6 ±12.6% to 13.0 ±10.5%; p < 0.05), which was consistent with BP increase. Changes in FMD were not significantly related to the increase in NO and TAS concentrations and decrease in ET-1 and peroxides measurements. Conclusions The hypotensive effect of atorvastatin is associated with FMD improvement in normolipidaemic, hypertensive patients. Although this could be related to changes in oxidative stress and endothelial function, this was not demonstrated in this study and warrants further investigation.

Enhanced IL-6 trans-signaling in pulmonary arterial hypertension and its potential role in disease-related systemic damage.

BACKGROUND The role of IL-6 in pulmonary arterial hypertension (PAH) has been reported but the prevalence of soluble receptors for IL-6: sIL-6R and sgp130 and its potential role in PAH have not been studied.Our aim was to examine the IL-6 together with the soluble receptors and to assess its relationship with clinical status of PAH patients as well as to assess its potential prognostic significance. METHODS Serum concentrations of IL-6, sIL-6R and sgp130 were quantified by ELISA in 26 patients with PAH and 27 healthy controls and related to functional and biochemical parameters and clinical outcome in PAH group. The PAH patients were followed up for 1 year, noting the end point of clinical deterioration (WHO class change, the need for escalation of therapy) or death. RESULTS The PAH group was characterized by higher median serum IL-6 [2.38 (IQR 1.56-3.75) vs 0.87 (0.63-1.3) pg/ml, p=0.000003] and sIL-6R concentrations [69.7 (IQR 60.4-84.4 vs 45.7 (34.6-70.3) ng/ml, p=0.0036] compared to control subjects. Both groups did not differ in sgp130 concentrations. There were significant correlations in PAH group between IL-6 levels and uric acid, parameters of ventilatory efficiency in cardiopulmonary exercise testing: VE/VO2, VE/VCO2, VE/VCO2 slope and peak PetCO2. sIL-6R levels inversely correlated with LDL cholesterol. After 1 year the clinical deterioration occurred in 11 patients, 15 remained stable. Patients in whom the clinical deterioration occurred showed significantly higher baseline concentrations of IL-6 [3.25 (IQR 2.46-5.4) pg/ml vs 1.68 (1.38-2.78) pg/ml, p=0.004], but not sIL-6R. Median IL-6 ⩾ 2.3 pg/ml (91% sensitivity, 73% specificity) identified subjects with worse clinical course. In the univariate analysis, higher IL-6 level at baseline was associated with increased risk and earlier occurrence of clinical deterioration (HR 1.42, 95%CI 1.08-1.85, p=0.015). CONCLUSIONS IL-6 trans-signaling is enhanced in PAH. Elevated concentration of sIL-6R suggests its potential unfavorable role in systemic amplification of IL-6 signaling in PAH. Levels of IL-6 are associated with clinical indicators of disease severity as well as indirectly with systemic metabolic alterations. IL-6 shows prognostic value regarding predicting clinical deterioration.

Blood pressure in relation to neurogenic, inflammatory and endothelial dysfunction biomarkers in patients with treated essential arterial hypertension

PURPOSE Clinical relevance of relations among blood pressure (BP), inflammation, endothelial dysfunction and sympathetic activation is unknown. Study aimed, whether in patients with diagnosed and treated essential arterial hypertension (HTN) biomarkers of inflammation (hs-C-reactive protein, hs-CRP), endothelial dysfunction (endothelin-1, ET-1), and sympathetic nervous system modulation (epinephrine, E and norepinephrine, NE) could be related to BP values. MATERIAL AND METHODS In 62 patients with diagnosed and treated HTN (mean time of disease 5±3.2 years), serum hs-CRP and ET-1 as well as plasma E and NE concentrations were measured. 24-hour ambulatory blood pressure measurement device (ABPM) was used to estimate efficacy of treatment. RESULTS A positive correlation between epinephrine and norepinephrine concentrations was found (r=0.246, p=0.05), however such a statistically significant correlation neither to hs-CRP, nor ET-1 were found. Patients with the highest hs-CRP and NE concentrations had the highest systolic (SBP) and diastolic (DBP) blood pressure values. Similar relation was found in subgroup of patients with suboptimal blood pressure values (SPB ł 130mmHg, DBP ł 80mmHg). In a group of optimal treated patients, elevated levels of ET-1 and NE related to increased blood pressure values. ROC analysis identified ET-1 as statistically significant to diagnose elevated blood pressure: 0.665 (95% Confidence interval 0.512 to 0.796). CONCLUSIONS In patients with diagnosed and treated arterial hypertension, there are relations among measurements of hs-CRP, ET-1, NE and blood pressure values in spite of treatment, which may improve understanding of mechanisms involving inflammation, endothelial dysfunction and sympathetic nerve activation and may identify patients with refractory hypertension.

Myocardial perfusion assessed by contrast echocardiography correlates with angiographic perfusion parameters in patients with a first acute myocardial infarction successfully treated with angioplasty

BACKGROUND Angiographic flow in an epicardial artery does not define perfusion at the microvascular level. AIM To compare myocardial contrast echocardiography (MCE) with angiographic methods of assessing microvascular reperfusion in patients with acute myocardial infarction (AMI). METHODS One hundred consecutive patients with a first ST segment elevation myocardial infarction and single-vessel disease were successfully treated with primary percutaneous coronary intervention. Regional contrast score index (RCSI), corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (cTFC), TIMI myocardial perfusion grade (TMPG) and myocardial blush grade were evaluated. RESULTS Among 717 asynergic segments on MCE, 168 revealed a lack of perfusion. TMPG and cTFC correlated significantly with RCSI (P=0.031 and P=0.027, respectively). Myocardial blush grade did not correlate with RCSI (P=0.067). Patients with anterior AMI had significantly more segments with a perfusion defect on MCE than patients with inferior AMI (P=0.0001). CONCLUSIONS MCE results correlate with angiographic methods of perfusion assessment such as TMPG and cTFC. Anterior AMI is associated with a greater extent of perfusion defect. MCE results correlate also with recovery of systolic left ventricular function and clinical outcome at six month follow-up.

Early and long-term prognosis of patients with coronary artery disease treated with percutaneous coronary interventions in 2005. Experience of single large-volume PCI center

PURPOSE The progress which has been made in interventional cardiology contributes to the gradual improvement of the results of CHD (coronary heart disease) therapy. The aim of the study was the assessment of early and long-term prognosis in all the patients with CHD treated invasively in one large-volume PCI center in 2005. MATERIAL AND METHODS 1390 consecutive patients with CHD treated with PCI in 2005 were included in the analysis. Patients with ST-elevation myocardial infarction (STEMI) accounted for 50% of cases, patients with stable angina (SA) amounted to 25%, and patients with non-ST elevation acute coronary syndromes (NSTE-ACS) constituted 25%. Mean follow-up was 738 (±237) days. RESULTS The highest mortality during the hospitalization was noted within the STEMI group(SA vs. NSTE-ACS vs. STEMI; 0% vs. 0.3% vs. 4.1%, respectively; p<0.001). The highest mortality during a 2-year follow-up was also observed in the STEMI group (SA vs. NSTE-ACS vs. STEMI, 6.3% vs. 8.5% vs. 13.8%, respectively; p<0.001). Multiple regression model showed that independent risk factors for death during the follow-up were: age, glycaemia at admission, heart rate, blood pressure, ejection fraction, STEMI, ineffective PCI (R=0.3613; F(10.131)=19.672; p<0.0001 for the model). CONCLUSIONS The highest relative increase of mortality after the discharge of patients with CHD undergoing PCI referred to the patients with NSTE-ACS. However, in the real life PCI practice STEMI patients have the worst hospital and long-term prognosis. Well recognized risk factors for death in patients with CHD are still of great importance in negative prognosis of patients undergoing PCI.