Maria Olszowska

Activated factor XI and tissue factor in aortic stenosis: Links with thrombin generation

In our previous studies, we showed that a significant proportion of patients with various cardiovascular diseases have active tissue factor (TF) and factor (F)XIa in their plasma. The objective of the present study was to evaluate these two proteins in plasma from patients with aortic stenosis and establish their relationship with the severity of the disease. Fifty-four consecutive patients with aortic stenosis, including 38 (70.4%) severe aortic stenosis patients, were studied. Plasma FXIa and TF activity were determined in clotting assays by measuring the response to inhibitory monoclonal antibodies. TF activity was detectable in plasma from 14 of 54 patients (25.9%), including 13 of 38 with severe aortic stenosis (34.2%) and one of 16 (6.25%) with moderate aortic stenosis (P = 0.052). FXIa activity was found in 12 (22.2%) patients, mostly in individuals with severe aortic stenosis (11 of 38, 28.9%, P = 0.067). All 12 patients with circulating FXIa had active TF in their plasma as well. Severe aortic stenosis patients with detectable TF had higher maximal (111 ± 20 vs. 97 ± 16 mmHg, P = 0.02) and mean (61 ± 12 vs. 53 ± 8 mmHg, P = 0.02) transvalvular gradient, compared with those without such activity in plasma. In severe aortic stenosis patients with detectable active TF, prothrombin fragment 1.2, a thrombin generation marker, was higher than that in patients without TF (375 ± 122 vs. 207 ± 64 pM, P < 0.001). Detectable FXIa and TF activity was observed for the first time in aortic stenosis patients, primarily in severe ones. This activity correlates with thrombin generation in those patients.

Iron deficiency and hematological changes in adult patients after Fontan operation

BACKGROUND Growing evidence indicates that iron-deficiency anemia is common in patients with congenital heart diseases. The aim of this study was to characterize hematologic changes and iron metabolism in adult Fontan patients. We also searched for the associations between these parameters and physical performance in the study group. METHODS AND RESULTS Thirty-two white Fontan patients with a mean age of 25 ± 4.5 years and 30 healthy control subjects matched for age and sex were studied. Complete blood count together with iron-related parameters was determined in plasma of peripheral venous blood. The cardiopulmonary exercise test was performed. The Fontan patients had higher red blood cell counts (6.0 ± 2.1 × 10(9)/μl vs. 4.8 ± 0.4 × 10(9)/μl, p<0.001), hemoglobin (16.7 ± 1.4 g/dl vs. 14.2 ± 1.3g/dl, p<0.001), hematocrit (49 ± 3.4% vs. 42.1 ± 3.1%, p<0.001), red cell distribution width (RDW) (14.3 ± 2.4% vs. 12.8 ± 0.5%, p<0.001), while mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were similar in both the groups. Compared to the controls, the Fontan patients had higher unsaturated iron binding capacity (46.1 ± 12.6 μmol/l vs. 38.4 ± 11.9 μmol/l, p=0.02), total iron-binding capacity (62.8 ± 9.8 μmol/l vs. 57.8 ± 8.5 μmol/l, p=0.04), lower transferrin saturation (27.4 ± 11.4% vs. 34.6 ± 13.4%, p=0.03), and oxygen uptake, while iron and ferritin levels were comparable in both the groups. The multivariate model showed that SatO2 and cystatin C were independent predictors of RDW, and alanine aminotransferase was an independent predictor of ferritin level. Interestingly RDW was an independent predictor of oxygen uptake. CONCLUSION Adult patients after Fontan operation despite having increased hemoglobin, hematocrit, and red blood cells have insufficient iron stores. Red cell distribution width is an indicator of iron deficiency in adult Fontan patients and it correlates with lower exercise capacity. Elevated ferritin levels in adult patients after Fontan surgery are associated with liver failure.

Nonstenotic bicuspid aortic valve is associated with elevated plasma asymmetric dimethylarginine.

Background Recently, it has been reported that nonstenotic bicuspid aortic valve (BAV) with dilated proximal aorta is linked with increased matrix metalloproteinase-2 (MMP-2) and endothelial dysfunction. Objective We wondered whether asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, might be altered and associated with MMP-2 in BAV patients. We assessed the relation between ADMA levels and aortic diameters and hypothesized that elevated ADMA might be an independent predictor of progressive aortic dilatation in BAV patients. Methods We studied 20 patients with nonstenotic BAV (17 men and 3 women, median age 27, range 24–33 years). Twenty age-matched patients with tricuspid aortic valves served as controls. Plasma levels of ADMA, symmetric dimethylarginine (SDMA), L-arginine, serum MMP-2, MMP-9, and plasma total homocysteine (tHcy), together with parameters of aortic elasticity, were measured. Results ADMA and MMP-2 levels were higher in the BAV group compared with controls (medians, 0.55 vs. 0.43 &mgr;mol/l, P < 0.001 and 1.25 vs. 1.00 &mgr;mol/l, P < 0.001, respectively). The BAV patients also had higher SDMA and tHcy levels than controls (0.39 vs. 0.35 &mgr;mol/l, P < 0.001 and 11.5 vs. 9.7 &mgr;mol/l, P = 0.006). ADMA levels in BAV patients correlated with aortic annulus (r = 0.4, P = 0.043), peak aortic velocity (r = 0.6, P = 0.001), aortic distensibility (r = 0.6, P = 0.004), aortic stiffness index (r = 0.7, P < 0.001), and aortic strain (r = 0.7, P < 0.001) as well as with MMP-2 (r = 0.6, P = 0.002) and tHcy (r = 0.4, P = 0.042). Conclusions This study is the first to show that circulating ADMA together with MMP-2 is a marker of proximal ascending aortic dilatation and impaired aortic elastic properties in nonstenotic BAV patients. It might be speculated that plasma ADMA could be helpful in identifying BAV patients at a higher risk of aortic aneurysm.

Assessment of left ventricle function in patients with symptomatic and asymptomatic aortic stenosis by 2-dimensional speckle-tracking imaging

Summary Background Global longitudinal peak strain (GLPS) quantifies left ventricle (LV) long-axis contractility. Early detection of LV systolic dysfunction is pivotal in diagnosis and treatment of patients with aortic stenosis (AS). This study was performed to assess LV longitudinal systolic function by GLPS derived from 2-dimensional speckle tracking imaging (2D-STI) in AS patients in comparison to standard echocardiographic parameters. Material/Methods Laboratory tests, standard echocardiography, tissue Doppler imaging (TDI) and 2D-STI examinations with GLPS calculation were performed in 49 consecutive patients with moderate to severe AS with LV ejection fraction ≥50% and 18 controls. Results While LVEF do not differentiate AS patients from controls, GLPS was significantly decreased in the AS group (−15.30±3.25% vs. −19.60±2.46% in controls, p<0.001). GLPS was significantly reduced in symptomatic AS patients as compared to the asymptomatic AS group [−15.5 (11.8–16.8) vs. −17.5 (14.7–18.9)%, p=0.02]. Conclusions In aortic stenosis patients, despite normal left ventricle ejection fraction, long-axis left ventricular function is impaired, which manifests in global longitudinal peak strain reduction. GLPS reveals that LV function impairment is more pronounced in symptomatic as compared to asymptomatic AS patients. Further studies are needed to determine the prognostic significance of early LV function impairment in aortic stenosis patients showed by GLPS.

Aspirin resistance in adult patients after Fontan surgery

BACKGROUND Thrombotic complications are common in adult patients who have had a Fontan operation early in life for treatment of congenital heart disease. OBJECTIVE To characterize platelet function and responsiveness to aspirin in relation to thrombogenesis, systemic inflammation, and markers of endothelial function in adults with Fontan circulation (FC). METHODS Thirty-four FC patients (age 18-40years; 62% taking aspirin chronically and 38% not taking aspirin) and 32 age- and sex-matched healthy controls were studied. Platelet function was evaluated by measurement of basal concentrations of thromboxane B2 (TXB2) and sCD40L and ex-vivo generation of TXB2 and sCD40L. Plasma concentrations of thrombin-antithrombin, endothelin-1, vWF, IL-6, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 also were measured. RESULTS Platelet numbers were significantly lower in FC patients than in controls, but the patients had significantly higher platelet activity, as evidenced by higher TXB2 and sCD40L concentrations and higher ex vivo generation of TXB2. Chronic aspirin treatment had no effect on plasma concentrations of TXB2 and sCD40L in FC, but in 52% of aspirin-treated FC subjects, TXB2 concentrations remained elevated at 60min of TXB2 generation, indicating aspirin resistance. In addition, FC patients had increased levels of thrombin-antithrombin, endothelin-1, vWF, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 but not of IL-6. CONCLUSION Adults with FC had lower platelet numbers but increased platelet activity, increased thrombogenesis, systemic inflammation, and endothelial dysfunction. A significant proportion of aspirin-treated FC adults had aspirin resistance, which may be at least in part responsible for their increased incidence of thrombotic complications.

Secondary prevention in patients after hospitalisation due to coronary artery disease: what has changed since 2006?

BACKGROUND The evidence concerning the quality of secondary prevention of coronary artery disease (CAD) in Poland in recent years is scarce. AIM To compare the implementation of secondary prevention guidelines into everyday clinical practice between 2006-2007 and 2011-2012 in patients after hospitalisation due to CAD. METHODS Five hospitals with departments of cardiology serving a city and its surrounding districts in the southern part of Poland participated in the study. Consecutive patients aged ≤ 80 years, hospitalised from April 1, 2005 to July 31, 2006 (first survey) and from April 1, 2010 to June 30, 2011 (second survey) due to acute coronary syndrome or for a myocardial revascularisation procedure were recruited and interviewed 6-18 months after hospitalisation. RESULTS Medical records of 640 patients were reviewed and included in the first survey and 466 in the second survey. The proportion of medical records with available information on smoking did not differ between the surveys, whereas the proportion of medical records with available information on blood pressure and total cholesterol was lower in patients hospitalised in 2010-2011. The prescription rate of β-blockers at discharge decreased from 90% to 84% (p < 0.05), whereas the prescription rates at discharge of other drug classes did not change significantly. The proportion of patients with high blood pressure (≥ 140/90 mm Hg) one year after hospitalisation decreased in 2011-2012 compared to 2006-2007 (from 48% to 35%, p < 0.05), whereas the proportion of subjects with high LDL cholesterol, high fasting glucose, and obesity did not change significantly. We did not note a significant difference in the smoking rate. The proportions of patients taking an antiplatelet agent (90% vs. 91%), a β-blocker (87% vs. 79%), an ACE inhibitor or a sartan (79% vs. 76%), a calcium antagonist (22% vs. 25%), a diuretic (35%vs. 45%), and a lipid-lowering drug (86% vs. 87%) one year after discharge did not change significantly (all p > 0.05). CONCLUSIONS We noted a modest improvement in the implementation of CAD secondary prevention guidelines in everyday clinical practice: blood pressure was better controlled, although the control of all other main risk factors did not change significantly. Our data provides evidence that there is a considerable potential for further reduction of cardiovascular risk in CAD patients.

Establishing the optimal dose of nitric oxide in acute vasoreactivity testing in patients with pulmonary hypertension with use of the Bronchial Control Treatment System (RCD code: II)

The key point in the diagnostic algorithm for pulmonary hypertension plays the pulmonary reactivity testing, the agent most frequently used in the test is inhaled nitric oxide (iNO). Various dosages of iNO were used in acute vasoreactivity testing so far, so we aimed to determine the most effective dose of iNO administered in the acute vasoreactivity testing. Ten consecutive patients was enrolled to the open label study. To assess the most effective dose of iNO increasing concentrations of iNO: 10 ppm, 20 ppm and 30 ppm were administered. In the study statistically significant reduction in mean pulmonary artery pressure after each dose of iNO as compared to baseline was found. There were no significant differences in mean pulmonary artery pressure between subsequent iNO doses (10 ppm vs. 20 ppm, 20 ppm vs. 30 ppm). Statistically significant reduction of systolic pulmonary artery pressure after iNO at the dose of 20 ppm as compared to a dose of 10 ppm was observed. No significant side effects during iNO administration were observed. We concluded that the dose of inhaled nitric oxide used in the acute vasoreactivity testing should not exceed 20 ppm, it is effective and safe dose.

Transcatheter closure of atrial septal communication: impact on P-wave dispersion, duration and arrhythmia in mid-term follow-up

BACKGROUND Atrial septal communications (ASCs) include atrial septal defects (ASDs) and patent foramen ovale (PFO). AIM The purpose of this study was to assess P-wave dispersion (PWD) and the prevalence of arrhythmia in patients before and after ASC closure. METHODS We analysed the clinical history and performed 12-lead electrocardiograms, echocardiograms, and 24-h Holter electrocardiograms in patients with ASC, before and six months after ASC closure. RESULTS We included patients with ASD (n = 56) and PFO (n = 73). PWD before percutaneous ASC closure was predicted by right ventricular outflow tract (RVOT) proximal diameter, left atrial area, ASD, smoking, and paroxysmal dyspnoea, R2 = 0.67; p < 0.001. RVOT proximal diameter was an independent predictor of PWD, both in patients with ASD and PFO. Six months after successful closure of ASC, a reduction in PWD was observed in the whole group of patients as well as in patients with ASD and PFO considered separately. A decrease in PWD was associated with reduction of maximum P-wave duration. At the same time, in the whole group, we noticed a reduction in the number of supraventricular and ventricular extrasystolic beats and fewer atrial fibrillation (AF) episodes, p < 0.04 for all variables. Postprocedural AF episodes in patients with ASD were predicted by PWD of 80 ms. CONCLUSIONS Percutaneous closure of ASC is associated with a reduction of PWD and fewer arrhythmia episodes six months after the procedure. PWD predicts AF episodes after ASD closure.