Władysław Sinkiewicz

Tissue‐factor‐bearing microparticles (MPs‐TF) in patients with acute ischaemic stroke: the influence of stroke treatment on MPs‐TF generation

Stroke is an important cause of death and disability throughout the world. Microparticles play a cardinal role in vascular hemostasis. The primary aim of this study was to evaluate the procoagulant activity of microparticles and levels of tissue‐factor‐bearing microparticles (MPs‐TF), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with acute ischaemic stroke.

Autonomic nervous function in Helicobacter pylori-infected patients with atypical chest pain studied by analysis of heart rate variability.

Objectives Cardiovascular autonomic neurous system (ANS) activity estimated by analysis of heart rate variability (HRV) was compared in Helicobacter pylori-positive and H. pylori-negative male patients suffering from atypical chest pain to verify the hypothesis that autonomic neural system might be the way linking chronic H. pylori infection with gastrointestinal tract disorders. Methods We have analysed data obtained from 101 male patients examined in our clinic due to atypical chest pain, without evidence of serious cardiovascular, respiratory and digestive tract or metabolic diseases. In each patient, besides interview and physical examination, were performed: gastroscopy with mucosa biopsy (for urease test and histology), oesophageal pH-metry and manometry, ultrasound abdomen examination, chest X-ray, exercise test on running track, 24-h ECG Holter monitoring with time-domain and frequency-domain HRV analysis, and echocardiography. Results In comparison with H. pylori-negative, in all H. pylori-infected patients (n = 63) a significantly greater low frequency power, an index of sympathetic activity, and higher values of vagal tone parameters [pNN50, percentage of differences between RR intervals that are greater than 50 ms; high-frequency power in HRV analysis (HF)] were observed. The relationship between H. pylori infection and the HF value was confirmed in multi-factorial analysis. The aforementioned ANS activity differences were accompanied by: significantly fewer gastro-oesophageal acid reflux episodes, lower gastric acidity and more effective and complete oesophageal peristalsis in H. pylori-positive patients. Conclusions H. pylori infection may affect ANS activity and via this way also contribute to gastro-oesophageal and cardiovascular pathology.

Relationship between B-type natriuretic peptide serum level, echocardiographic TEI index and the degree of diastolic dysfunction in patients with heart failure with preserved systolic function

Introduction The growing number of heart failure (HF) patients is becoming an important issue in cardiology. B-type natriuretic peptide (BNP) is a recognized marker of HF, including in patients with preserved systolic function. The TEI index is an indicator of left ventricular function. The aim of the study was to evaluate the relationship between BNP serum level, TEI index and the degree of diastolic dysfunction in patients with HF symptoms and preserved systolic function. Material and methods Hundred patients with arterial hypertension and preserved systolic function were enrolled in the study. The study group consisted of 51 individuals with impaired diastolic function and HF symptoms. Fourty-nine hypertensive individuals without HF symptoms were assigned to the control group. B-type natriuretic peptide and echocardiographic examination were performed. Patients were divided into 4 subgroups – with normal diastolic function, impaired relaxation, pseudonormalization and restriction. Results Median value of BNP in patients with normal diastolic function was 28.36 pg/ml, 87.10 pg/ml in patients with impaired relaxation, 212.75 pg/ml and 461.56 pg/ml in the pseudonormalization and restriction group respectively (p < 0.0001). The median value of the TEI index was: 0.386 in patients with normal diastolic function, 0.507 in individuals with impaired relaxation, 0.639 and 0.725 in the pseudonormalization and restriction group respectively. All the differences were statistically significant (p < 0.0001). A significant positive correlation (r = 0.80, p < 0.001) between BNP and the TEI index was found. Conclusions In hypertensive patients with HF symptoms and preserved left ventricular systolic function a highly significant increase in BNP serum level and in the TEI index values related to the deterioration of diastolic dysfunction was found.

Short-term alcohol consumption may have detrimental effect on fibrinolysis and endothelial function: preliminary report of prospective randomised study

BACKGROUND AND AIM This study was designed to clarify the impact of the short-term consumption of different types of alcoholic beverages on haemostatic factors, C-reactive protein (hsCRP) and endothelin-1 (E-1) plasma levels. METHODS The study group consisted of 57 healthy male volunteers, aged 20-29 years. Subjects were randomised to consume 300 mL of red wine, white wine, 12% ethanol, black currant juice or water for five days. Blood samples were collected for CRP, tissue type plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor antigen (PAI-1:Ag) and E-1 at baseline, on day 2, and on day 6. RESULTS A significant increase in PAI-1:Ag concentration was observed in the red wine drinking group (day 1: 44.98; day 2:56.86; day 6: 47.44 ng/mL; p = 0.05). A similar increase of E-1 level was found in the 12% ethanol group (day 1: 0.53; day 2:1.65; day 6: 1.11 fmol/mL; p = 0.01). Dividing the whole study group according to ethanol content of consumed beverages revealed significant changes in tPA:Ag, PAI-1:Ag and E-1 levels. In the alcohol drinking group, significant increases of PAI-1:Ag (day 1: 44.75; day 2: 54.07; day 6: 44.80 ng/mL; p < 0.05); tPA:Ag level (day 1: 3.65; day 2: 4.17; day 6: 5.03 ng/mL;p < 0.02) and E-1 (day 1: 0.42; day 2: 1.01; day 6: 0.97 fmol/mL; p < 0.002) were observed. CONCLUSIONS Short-term alcohol consumption increases tPA:Ag, PAI:Ag and E-1 plasma levels. This effect may have an unfavourable impact on the fibrinolytic system and endothelial function.

Haemostatic factors do not account for worse outcomes from ischaemic stroke in patients with higher C-reactive protein concentrations:

Background Although the role of microparticles was recently implicated in stroke pathophysiology, the association between microparticles and inflammation is still not fully understood. The aim of this cohort study of 66 patients was to assess a relation between haemostatic factors, C-reactive protein and clinical outcome of ischaemic stroke. Methods Plasma microparticles procoagulant activity, concentrations of tissue factor-bearing microparticles, tissue factor and tissue factor pathway inhibitor in ischaemic stroke patients were determined with enzyme-linked immunosorbent assays at the time of initial diagnosis, along with serum C-reactive protein concentrations. Patients were divided into two groups depending on their C-reactive protein concentrations (C-reactive protein <3 mg/L; n = 28 vs. C-reactive protein ≥3 mg/L; n = 38). The analysed clinical outcome measures included the National Institutes of Health Stroke Scale and the Barthel Index. Results The two C-reactive protein groups did not differ significantly in terms of microparticles procoagulant activities, tissue factor-bearing microparticles, tissue factor and tissue factor pathway inhibitor concentrations. A significant correlation was observed between tissue factor pathway inhibitor and National Institutes of Health Stroke Scale score at admission (R = 0.3, P = 0.03). Patients with C-reactive protein ≥3 mg/L presented with significantly higher National Institutes of Health Stroke Scale scores (median, 9.00 vs. 5.50, P = 0.002) and lower Barthel Index scores (median, 20.00 vs. 65.00, P = 0.002) than individuals with C-reactive protein <3 mg/L. The C-reactive protein concentrations correlated positively with National Institutes of Health Stroke Scale scores (R = 0.3, P = 0.02) and inversely with Barthel Index scores (R = − 0.4, P = 0.002). Conclusions Altogether, these findings imply that haemostatic parameters (microparticles, tissue factor-bearing microparticles, tissue factor, tissue factor pathway inhibitor) do not account for elevated C-reactive protein concentrations in ischaemic stroke patients.

Melanoma cell adhesion molecule as an emerging biomarker with prognostic significance in systolic heart failure

BACKGROUND Melanoma cell adhesion molecule (MCAM) is a marker of endothelial damage. MCAM diagnostic and prognostic value was assessed in chronic heart failure (CHF). MATERIALS & METHODS 130 CHF patients and 32 controls were included in the study. Telephone follow-up lasted one year. End points were: death from all causes, and hospitalization with CHF exacerbation. RESULTS MCAM was higher in patients than in controls (p = 0.01). Receiver operator curve analysis revealed that MCAM may serve as a predictor of death (area under the curve: 0.8404; p < 0.002). Patients with MCAM above 500 ng/ml had worse prognosis (p = 0.03). NT-proBNP and age were independent predictors of death in multivariate analysis. CONCLUSION The increased MCAM indicates endothelial damage in CHF and may serve as a marker of worse prognosis in these patients.

Low-dose dobutamine stress echo for reverse remodeling prediction after cardiac resynchronization

PURPOSE Cardiac resynchronization therapy (CRT) is a valuable option for patients with heart failure and wide QRS to reduce electromechanical dyssynchrony (DYS). High non-responders rate (30%) urges the need to improve selection of candidates for CRT. We hypothesized that low-dose dobutamine stress echocardiography (DSE) can help unmask dyssynchronous motion. The aim of this study is comparison between dyssynchrony index at rest and during low-dose dobutamine stress to predict left ventricular reverse remodeling after CRT. PATIENTS AND METHODS Prospectively, 57 consecutive patients (37 male) aged 61.8±9 who qualified for CRT according to current guidelines were enrolled. Two dimensional echocardiography and tissue Doppler imaging (TDI) were performed before and 6 month after CRT to assess reverse remodeling (rLV). Additionally DSE was performed before CRT. DYS was assessed at rest (DYSr) and peak DSE (DYSd) separately, as a difference between time to peak systolic velocity (Ts) of septum and lateral wall. Ts was corrected for heart rate. RESULTS rLV defined as decrease ≥15% of LVESV at follow-up was found in 38 (67%) patients. DYSr and DYSd were independent predictors of rLV (OR=1.04, Cl ±1.02-1.06, p<0.02 and OR=1.05, Cl±1.03-1.08, p<0.0002 respectively). ROC analysis found that DYSr>42ms and DYSd>59ms had sensitivity of 70% and 87%, specificity of 61% and 78%, and accuracy of 70% and 84% respectively for prediction of reverse remodeling LV. Area under Receiver Operating Characteristic Curve for DYSd was higher than for DYSr (0.89 vs 0.71, p<0.007). CONCLUSION Exercise intraventricular dyssynchrony assessed by dobutamine stress echo is a strong independent predictor of cardiac resynchronization therapy response.

Assessing Circulating Factor VIIa–Antithrombin Complexes in Acute Ischemic Stroke: A Pilot Study:

Aim: The goal of this study was to determine the levels of factor VII (FVII), factor VIIa–antithrombin complexes (FVIIa-AT), total tissue factor (TF), and tissue factor-bearing microparticles (MPs-TF) in patients with acute ischemic stroke. Further, we sought evidence of an association between hemostatic markers, time of blood sampling, type of treatment, and patient outcomes. Methods: Venous blood samples were collected from 33 patients on the first day and on the seventh day after stroke diagnosis. Age-matched controls were also included (n = 20). Plasma levels of FVII, FVIIa-AT, total TF, and MPs-TF were measured by enzyme-linked immunosorbent assay. We divided patients into 2 groups: thrombolysis group (n = 13) and nonthrombolysis group (n = 20). Furthermore, evaluation of the National Institutes of Health Stroke Scale and the Barthel Index was performed on the first day and the seventh day. Results: Patients with ischemic stroke showed significantly lower plasma FVII, FVIIa-AT, and total TF levels than controls (median, 112.25% vs 132.05%, P = .004; 107.97 pmol/L vs 154.94 pmol/L, P < .001; 81.74 pg/mL vs 105.71 pg/mL, P < .001, respectively). In contrast, levels of plasma MPs-TF were significantly higher in patients with stroke compared to healthy controls (1.60 pg/mL vs 0.74 pg/mL, P < .001). Additionally, the thrombolysis group had lower FVII levels on the seventh day compared to the first day (median, 109.80% vs 115.74%, P = .04). Conclusion: Factor VII, FVIIa-AT, and total TF are decreased, while MPs-TF are elevated in patients with ischemic stroke. We observed a slight but significant effect of alteplase on FVII plasma levels.

Predictors of functional mitral regurgitation improvement during a short-term follow-up after cardiac resynchronisation therapy

BACKGROUND AND AIM The study was undertaken to assess the predictive role of myocardial contractile reserve for functional mitral regurgitation (FMR) improvement after cardiac resynchronisation therapy (CRT), and to define other predictors of FMR improvement (FMRI) and the impact of FMRI on left ventricular (LV) reverse remodelling. METHODS AND RESULTS Among 90 patients in whom echocardiography was performed one day before and six weeks after CRT implantation, 66 with at least FMR(2+) in a four-point scale (mean age 64 ± 10 years, mean LV ejection fraction [LVEF] 25.7 ± 6%, ischaemic aetiology 48%) were included. FMRI was defined as the reduction of the FMR severity by at least one grade. The patients were divided into groups: A with FMRI (n = 30) and B without FMRI (n = 36). Contractile reserve was evaluated using low-dose dobutamine stress-echo before CRT implantation and was defined as a relative improvement in LVEF of more than 20% and segmental contractility improvement. Reverse remodelling was defined as the reduction of the LV end-systolic volume (LVESV) by at least 15%. Cox regression multivariate analysis revealed the following predictors for FMRI: contractile reserve preserved in more than three segments with an OR = 5.7 (95% CI 1.81-17.97, p = 0.005, sensitivity 65.5%, specificity 72.2%, AUC = 0.727) and LV end-diastolic diameter ≤ 74 mm with an OR = 2.09 (95% CI 0.75-5.78, p < 0.05, sensitivity 80.0%, specificity 47.2%, AUC = 0.632). FMRI was associated with greater reduction of LVESV (p = 0.002), greater increase in LVEF (p < 0.001) and higher incidence of the LV reverse remodelling (p < 0.001). CONCLUSIONS Preserved contractile reserve and lesser degree of LV dilation were predictive factors of short-term FMR improvement after CRT implantation. FMR improvement was associated with higher incidence of the LV reverse remodelling early, already in the six weeks after CRT implantation.

The autonomic imbalance in chronic heart failure: prognostic value of dynamic electrocardiographic risk markers

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