Paraoxonase 2 C311S single nucleotide polymorphism is associated with type C lesions in coronary atherosclerosis.

BACKGROUND: Paraoxonases (PON) 1-3 are lactonases with antioxidant and atheroprotective properties. The best known single nucleotide polymorphisms (SNPs) within the PON family, include: Q192R (rs662), L55M (rs854560) in the PON1 gene and C311S (rs7493) in the PON2 gene. Their influence on the occurrence and course of coronary artery disease (CAD) is unclear. The aim of this study was to assess the association between the most common PON1 and PON2 genetic variants with the presence of CAD, as well as their relation to coronary lesion complexity in accordance with the ACC/AHA standard. METHODS: We included 1027 individuals: 367 CAD patients qualified for coronary angiography and 660 healthy volunteers as controls. We extracted DNA from circulating blood leukocytes, amplified the PON1 and PON2 genetic sequence and used restriction enzymes to identify the SNPs. Patients with CAD underwent coronary angiography and were assigned to two groups based on lesion severity: patients with at least one type C lesion and without a type C lesion. The former where categorized into those with a significant narrowing (≥50% diameter stenosis) and those without one. RESULTS: We found no association between the analyzed SNPs and symptomatic CAD. However, in patients with diagnosed CAD, the PON311S allele was independently associated with the risk of the most complex type C coronary lesion occurrence. CONCLUSIONS: Our study is the first report of an association between PON2 311S SNP and the type of coronary atherosclerotic lesions in humans.

"Heart without smoke" educational campaign - the role of patient education in secondary prevention of cardiovascular disease.

BACKGROUND: Nicotine addiction is the strongest factor in the increase of the risk of recurrent ischaemic events. AIM: The aim of the study was to analyse the effectiveness of a smoking cessation educational programme in a population of patients hospitalised with acute myocardial infarction within the "Heart without smoke" campaign. METHODS: In this study, we included 100 consecutive patients, active smokers, hospitalised with acute myocardial infarction (STEMI or NSTEMI) at the Centre for Invasive Cardiology, Angiology, and Electrotherapy in Pinczow, Poland in the period from January to December 2015 (12 months). Patients were participants in the educational campaign about tobacco addiction "Heart without smoke". RESULTS: At one-month follow-up observation: 61 patients had quit smoking and an additional 35 had decreased the number of cigarettes smoked per day. During six-month follow-up interview: 51 patients did not smoke cigarettes (13 had returned to smoking, three had additionally stopped smoking, one person had died). There were no statistically significant correlations between smoking cessation and gender (p = 0.4; p = 0.2), age (p = 0.8; p = 0.8) and length of prior smoking habit (p = 0.8; p = 0.5) and daily cigarette consumption before myocardial infarctions (p = 0.3; p = 0.3), one month, and six months after hospital discharge, respectively. CONCLUSIONS: Constant education of patients after myocardial infarction was an effective method for smoking cessation in over 50% of smokers six months after myocardial infarction.

EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention.

AIMS: Among patients with ST-elevation myocardial infarction (STEMI), reperfusion injury contributes to additional myocardial damage. MTP-131 is a cell-permeable peptide that preserves the integrity of cardiolipin, enhances mitochondrial energetics, and improves myocyte survival during reperfusion. METHODS AND RESULTS: EMBRACE STEMI is a multicentre, randomized, double-blind Phase 2a trial that evaluated the efficacy and safety of MTP-131 vs. placebo infused at a rate of 0.05 mg/kg/h for 1 h among first-time anterior STEMI subjects undergoing primary percutaneous coronary intervention (PCI) for a proximal or mid left anterior descending (LAD) artery occlusion. Administration of MTP-131 was not associated with a significant reduction in the primary endpoint, infarct size by creatine kinase-myocardial band (CK-MB) area under the curve (AUC) over 72 h (5785 ± 426 ng h/mL in placebo vs. 5570 ± 486 ng h/mL in MTP-131; ITALIC! P = NS). MTP-131 was not associated with an improvement in pre-specified magnetic resonance imaging, angiographic, electrocardiographic, or clinical outcomes. CONCLUSION: Among subjects with first-time anterior STEMI due to a proximal or mid LAD lesion who undergo successful PCI, administration of MTP-131 was safe and well tolerated. Treatment with MTP-131 was not associated with a decrease in myocardial infarct size as assessed by AUC0-72 of CK-MB.

Polymorphism rs7023923 and monocyte count in blood donors and coronary artery disease patients.

BACKGROUND: The importance of the role of monocytes in coronary artery disease (CAD) is well documented. An increased number of circulating monocytes is associated with higher incidence of CAD. Both environmental and genetic factors influence monocytosis. The latter have been extensively studied since the development of high-throughput genome-wide association studies. Several associations between polymorphisms and monocytosis were found among healthy individuals; the first example was rs7023923. The magnitude of the association of studied polymorphisms with the trait of interest is often confounded by environmental factors and may therefore differ between patient and healthy populations. It is very important to determine the magnitude of the association among patients to predict outcome of the disease, e.g. myocardial infarction. AIM: To determine whether the magnitude of association of rs7023923 with monocytosis, previously reported among healthy volunteers, is similar in patients in whom diagnosis of CAD was determined during elective coronarography. METHODS AND RESULTS: Leucocytosis and neutrophilocytosis were higher among patients with CAD, while thrombocytosis was lower. Monocyte count did not differ among the studied groups (p = 0.25). We confirmed the association of rs7023923 with monocytosis among healthy blood donors (p = 0.0156) but not among patients admitted for elective coronarography (p = 0.61). Inclusion of the age and sex of patients in the statistical model did not modify the results. CONCLUSIONS: Our data suggest that translation of the results of genetic association with the studied traits from healthy to patient population should be implemented with caution. It is possible that numerous environmental factors, which discriminate healthy volunteers from CAD patients, confound the magnitude of genetic associations and make interpretation of the data in patients less clear.

Relationship between ST-segment resolution and anterior infarct size after primary percutaneous coronary intervention: analysis from the INFUSE-AMI trial.

AIMS: ST-segment resolution (STR) after reperfusion therapy has been shown to correlate with prognosis in patients with ST-segment elevation myocardial infarction (STEMI). We investigated whether acute ECG measurements also correlate with ultimate infarct size. METHODS AND RESULTS: The INFUSE-AMI trial randomized 452 patients with anterior STEMI to intracoronary bolus abciximab vs. no abciximab, and to thrombus aspiration vs. no aspiration. Infarct size as percentage of total LV mass was calculated by cardiac magnetic resonance imaging (MRI) 30 days post intervention. Five ECG methods were analysed for their ability to predict MRI infarct mass: (1) summed STR across all infarct-related ECG leads (ΣSTR); (2) STR in the single lead with maximum baseline ST-segment elevation (maxSTR); (3) summed residual ST-segment elevation across all infarct-related leads at 60 min post intervention (ΣST residual); (4) maximum residual ST-segment elevation in the worst single lead at 60 min post intervention (maxST residual); (5) number of new significant Q-waves (Qwave) at 60 min. All ECG methods strongly correlated with 30-day MRI infarct mass (all p<0.003). Simpler ECG measurements such as maxSTresidual and Qwave were as predictive as more complex measurements. A subset analysis of 158 patients who had microvascular obstruction (MVO) determined by MRI 5 days post intervention also showed strong correlations of MVO with the ECG measures. CONCLUSIONS: ST-segment and Q-wave changes after primary PCI in anterior STEMI strongly correlated with 30-day infarct size by MRI. In particular, maxST residual and Qwave at 60 min are simple ECG parameters that offer rapid analysis for prognostication.

Denervation of nerve terminals in renal arteries: one-year follow-up of interventional treatment of arterial hypertension.

BACKGROUND: Arterial hypertension is the most common cardiovascular system disease, affecting nearly one billion people worldwide. Despite the widespread use of antihypertensive medications, in some groups of patients an optimal blood pressure (BP) cannot be achieved. AIM: To assess BP reduction in patients with resistant hypertension after a catheter-based renal sympathetic denervation procedure and to report vascular and kidney safety in one-year follow-up. METHODS: Twenty eight patients with diagnosed resistant hypertension (median age 52.02 years, range 42-72) underwent percutaneous catheter-based renal denervation of nerve terminals in renal arteries. Arterial angiography and procedure of ablation was performed by Symplicity catheters and generator provided by Ardian (currently Medtronic Inc., USA). RESULTS: Mean BP value before ablation was [mm Hg]: systolic 176.6, diastolic 100.28 and pulse pressure 73.4. After the procedure, reductions in the value of BP were reported [mm Hg]: systolic 154.8/152.54; diastolic 90.2/89.8, pulse pressure 64.66/62.73, respectively in nine-month and one-year follow-up. All results were statistically significant. No complications during one year observation were observed. CONCLUSIONS: Percutaneous renal artery ablation procedure effectively reduces systolic BP, diastolic BP, and pulse pressure. No vascular or renal complications in any of the patients were observed. The results of a Polish research group showed no significant differences compared to the results obtained in the international studies Symplicity I and Symplicity II.

Intralesional abciximab and thrombus aspiration in patients with large anterior myocardial infarction: one-year results from the INFUSE-AMI trial.

BACKGROUND: Whether intralesional abciximab administration and thrombus aspiration confer clinical benefits to patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction is controversial. METHODS AND RESULTS: A total of 452 patients with ST-segment-elevation myocardial infarction caused by proximal or mid left anterior descending artery occlusion undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation were randomized in a 2×2 factorial design to bolus abciximab delivered locally at the infarct lesion site versus no abciximab and to manual thrombus aspiration versus no aspiration. Treatment with intralesional abciximab, thrombus aspiration, or both therapies compared with no active therapy before stent implantation resulted in lower 1-year rates of death (4.5% versus 10.4%; P=0.03), severe heart failure (4.2% versus 10.3%; P=0.02), and stent thrombosis (0.9% versus 3.8%; P=0.046). Between 30 days and 1 year of follow-up, treatment with intralesional abciximab compared with no abciximab was associated with a lower rate of death (1.4% versus 4.9%; P=0.04) and composite major adverse ischemic events (3.3% versus 7.8%; P=0.04), with nonsignificantly different overall 1-year rates of mortality, composite ischemic events, and heart failure-related events. Thrombus aspiration compared with no aspiration was associated with lower rates of new-onset severe heart failure between 30 days and 1 year (0.9% versus 4.5%; P=0.02) and of rehospitalization for heart failure from randomization to 1 year (0.9% versus 5.4%; P=0.0008), with nonsignificantly different rates of mortality. CONCLUSIONS: Intralesional abciximab and thrombus aspiration may have long-term benefits in patients with anterior ST-segment-elevation myocardial infarction presenting early after symptom onset and undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00976521.

Relation between white blood cell count and final infarct size in patients with ST-segment elevation acute myocardial infarction undergoing primary percutaneous coronary intervention (from the INFUSE AMI trial).

Although it has been shown that elevated white blood cell count (WBCc) on presentation is associated with an increased risk of cardiac mortality in patients with ST-segment elevation myocardial infarction (STEMI), the responsible mechanisms are unknown. We therefore sought to investigate whether elevated WBCc is associated with increased infarct size measured with cardiac magnetic resonance imaging 30 days after primary percutaneous coronary intervention in the Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction trial. INFUSE AMI randomized patients with STEMI and proximal or mid-left anterior descending coronary artery occlusion to bolus intracoronary abciximab versus no abciximab and to manual aspiration versus no aspiration. WBCc at hospital admission was available in 407 of 452 randomized patients. Patients were stratified according to tertiles of WBCc. At 30 days, a significant stepwise increase in infarct size (percentage of total left ventricular mass) was apparent across tertiles of increasing WBCc (median [interquartile range] for tertiles I vs II vs III = 11.2% [3.8% to 19.6%] vs 17.5% [0.5% to 22.9%] vs 19.1% [13.7 to 26.0], respectively, p <0.0001). Absolute infarct mass in grams and abnormal wall motion score were also significantly increased across tertiles of WBC. By multivariate linear regression analysis, WBCc was an independent predictor of infarct size along with intracoronary abciximab randomization, age, time from symptom onset to first device, proximal left anterior descending location, and baseline TIMI flow of 0/1. In conclusion, in patients with anterior wall STEMI, an elevated admission WBCc is a powerful independent predictor of infarct size measured with cardiac magnetic resonance imaging 30 days after primary percutaneous coronary intervention.

Denervation (ablation) of nerve terminalis in renal arteries: early results of interventional treatment of arterial hypertension in Poland.

BACKGROUND: Arterial hypertension is one of the main causes of cardiovascular disease morbidity and overall mortality. AIM: To report the single centre experiences with changes in arterial blood pressure (BP) in patients after intra-arterial application of radiofrequency (RF) energy to cause renal sympathetic efferent and somatic afferent nerve and report vascular and kidney safety in a six month follow up. METHODS: Twenty-eight patients, with hypertension despite medical therapy (median age 52.02 years, range 42-72 years) consented to therapeutic renal nerve ablation. SIMPLICITY RF catheters and generator provided by Ardian (currently Medtronic Inc., USA) were used to perform renal artery angiography and ablation. RESULTS: The mean BP at baseline, and after one month, three months and six months were measured [mm Hg]: systolic 176.6; 162.3 (p = 0.004); 150.6 (p < 0.001); 147.2 (p < 0.001); diastolic 100.2; 90.3 (p < 0.001); 91.79 (p = 0.03); 88.5 (p < 0.001); pulse pressure 76.57; 75.18 (p = NS); 65.80 (p < 0.001); 62.15 (p < 0.001). Neither procedure-related nor therapy-related complications were reported in the six month follow up. CONCLUSIONS: In our cohort of patients, intra-arterial renal nerve denervation was not associated with either vascular or renal complications out to six months. Nerve ablation of renal arteries led to significant reduction of mean values of arterial systolic, diastolic BP and significant reduction of pulse pressure. The Polish experience is not significantly different compared to that reported in the Symplicity I and Symplicity II international cohorts. The long term durability of this therapy and its application to earlier stages of hypertension or other disease states will require further investigation.

Rationale and design of the EMBRACE STEMI study: a phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability and efficacy of intravenous Bendavia on reperfusion injury in patients treated with standard therapy including primary percutaneous coronary intervention and stenting for ST-segment elevation myocardial infarction.

BACKGROUND: Although significant efforts have been made to improve ST-segment elevation myocardial infarction (STEMI) outcomes by reducing symptom-onset-to-reperfusion times, strategies to decrease the clinical impact of ischemic reperfusion injury have demonstrated limited success. Bendavia, an intravenously administered mitochondrial targeting peptide, has been shown to reduce myocardial infarct size and attenuate coronary no-reflow in experimental modelswhen given before reperfusion. DESIGN: The EMBRACE STEMI study is a phase 2a, randomized, double-blind, placebo-controlled trial enrolling 300 patients with a first-time anterior STEMI and an occluded proximal or mid-left anterior descending artery undergoing primary percutaneous coronary intervention (PCI) within 4 hours of symptom onset. Patients will be randomized to receive either Bendavia at 0.05 mg/kg per hour or an identically appearing placebo administered as an intravenous infusion at 60 mL/h. The primary end point is infarct size measured by the area under the creatine kinase-MB enzyme curve calculated from measurements from the central clinical chemistry laboratory obtained over the initial 72 hours after the primary PCI procedure, and the major secondary end point is infarct size calculated by the volume of infarcted myocardium (late contrast gadolinium enhancement) on the day 4±1 cardiac magnetic resonance imaging. SUMMARY: EMBRACE-STEMI is testing the hypothesis that Bendavia, in conjunction with standard-of-care therapy, is superior to placebo for the reduction of myocardial infarction size among patients with first time, acute, anterior wall STEMI who undergo successful reperfusion with primary PCI and stenting.

Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial.

CONTEXT: Thrombus embolization during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy. OBJECTIVE: To determine whether bolus intracoronary abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. DESIGN, SETTING, AND PATIENTS: Between November 28, 2009, and December 2, 2011, 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion undergoing primary PCI with bivalirudin anticoagulation were randomized in an open-label, 2 x 2 factorial design to bolus intracoronary abciximab delivered locally at the infarct lesion site vs no abciximab and to manual aspiration thrombectomy vs no thrombectomy. INTERVENTIONS: A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6 F aspiration catheter. MAIN OUTCOME MEASURES: Primary end point: infarct size (percentage of total left ventricular mass) at 30 days assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab vs no abciximab groups (pooled across the aspiration randomization); major secondary end point: 30-day infarct size in the aspiration vs no aspiration groups (pooled across the abciximab randomization). RESULTS: Evaluable cMRI results at 30 days were present in 181 and 172 patients randomized to intracoronary abciximab vs no abciximab, respectively, and in 174 and 179 patients randomized to manual aspiration vs no aspiration, respectively. Patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [IQR, 7.4-31.3 g]; n = 184, vs 24.0 g [IQR, 12.1-34.2 g]; n = 175; P = .03) but not abnormal wall motion score (median, 7.0 [IQR, 2.0-10.0]; n = 188, vs 8.0 [IQR, 3.0-10.0]; n = 184; P = .08). Patients randomized to aspiration thrombectomy vs no aspiration had no significant difference in infarct size at 30 days (median, 17.0% [IQR, 9.0%-22.8%]; n = 174, vs 17.3% [IQR, 7.1%-25.5%]; n = 179; P = .51), absolute infarct mass (median, 20.3 g [IQR, 9.7-31.7 g]; n = 178, vs 21.0 g [IQR, 9.1-34.1 g]; n = 181; P = .36), or abnormal wall motion score (median, 7.5 [IQR, 2.0-10.0]; n = 186, vs 7.5 [IQR, 2.0-10.0]; n = 186; P = .89). CONCLUSION: In patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin anticoagulation, infarct size at 30 days was significantly reduced by bolus intracoronary abciximab delivered to the infarct lesion site but not by manual aspiration thrombectomy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00976521.

Number of microparticles generated during acute myocardial infarction and stable angina correlates with platelet activation.

BACKGROUND AND AIMS: Elevated levels of circulating microparticles (MPs) have been reported in patients with acute myocardial infarction (AMI) and coronary artery disease. Platelet activation and inflammation have been recognized during AMI and stable angina (SA). We hypothesize that the origin and count of MPs in AMI and SA patients are related to markers of inflammation and platelet activation. METHODS: Platelet, monocytes and endothelial MPs and surface P-selectin were determined in 12 AMI patients, 10 SA patients and 9 controls by flow cytometry. Plasma P-selectin, CD40 ligand (sCD40L) and interleukin 6 (IL-6) levels were evaluated by ELISA methods. RESULTS: The total MP count was compared in control subjects, AMI, and SA patients: 12,765 (8465) vs. 38,750 (11,931) vs. 29,715 (12,072) counts/µl (p = 0.01), respectively. Patients with AMI displayed higher levels of total and platelet origin- tissue factor-positive (CD42/CD142) MPs than patients with SA: 72.8 (6.2) vs. 56.2 (6.4) %, p = 0.001. Levels of soluble P-selectin were significantly elevated in patients with AMI as compared to SA patients: 146 (6.5) vs. 107 (2.7) ng/mL, p = 0.005; significant correlation between total MP count and relative number of CD34, CD51, CD42-positive MPs, and the P-selectin expression was observed in patients with AMI. CONCLUSIONS: Platelet activation in AMI is associated with increased generation of MPs not only from platelets, but also monocytes and endothelial cells. It suggests that interactions between platelets, monocytes and endothelial cells play an important role in the pathogenesis of myocardial ischemia.

Reduced clot permeability and susceptibility to lysis in patients with acute coronary syndrome: effects of inflammation and oxidative stress.

BACKGROUND: Stable angina is associated with unfavorable fibrin structure/function. It is not known how acute coronary syndromes (ACS) affect fibrin architecture. OBJECTIVE: We investigated fibrin clot properties and their determinants in ACS patients. PATIENTS AND METHODS: Clot permeability, turbidity and fibrinolysis were assessed in 40 patients with ACS versus 40 controls with stable angina matched for age, sex, and risk factors. RESULTS: Patients with ACS had lower clot permeability (p=0.001), faster fibrin polymerization (p=0.008), and prolonged fibrinolysis time (p<0.0001) than controls. C-reactive protein (CRP) and 8-epi-prostaglandin F(2alpha), a marker of oxidative stress, were the only independent predictors of clot permeability (R(2)=-0.74; p<0.0001 and R(2)=-0.65; p<0.0001, respectively) and fibrinolysis time in ACS patients (R(2)=0.60; p<0.0001 and R(2)=0.59; p=0.0002, respectively). In angina patients, fibrinogen and CRP predicted permeability (R(2)=-0.71; p<0.0001 and R(2)=-0.62; p<0.0001), and D-dimer predicted lysis time (R(2)=0.54; p=0.0005). In regression analysis models incorporating all patients, the only independent predictor of all clot variables was being an ACS patient (R(2) 0.51 to 0.85; p<0.001). CONCLUSIONS: This first study of clot properties in patients during an ACS demonstrated that compared with stable angina patients, their clots are composed of dense networks that are more resistant to lysis and these features are correlated with raised CRP and oxidative stress.

No-reflow phenomenon after acute myocardial infarction is associated with reduced clot permeability and susceptibility to lysis.

OBJECTIVE: We assessed the relationship between fibrin clot properties and the no-reflow phenomenon after primary coronary intervention (PCI). METHODS AND RESULTS: Epicardial blood flow was assessed by TIMI scale and corrected TIMI frame count (cTFC), and perfusion by TIMI Myocardial Perfusion Grade (TMPG) after PCI during ST-segment elevation myocardial infarction (STEMI). Fibrin clot permeability (K(s)) and susceptibility to lysis in assays using exogenous thrombin (t(50%)) and without thrombin (t(TF)) were determined in 30 no-reflow patients (TIMI < or = 2) and in 31 controls (TIMI-3) after uneventful 6 to 14 months from PCI. Patients with TIMI < or = 2 had lower K(s) by 18% (P<0.0001) and prolonged fibrinolysis by 33% for t(50%) (P<0.0001) and by 45% for t(TF) (P<0.0001). cTFC was correlated with K(s) (r=-0.56, P<0.0001), t(50%) (r=0.49, P<0.001), and t(TF) (r=0.54, P<0.001). K(s) increased in a stepwise fashion with TIMI flow (P<0.0001) and TMPG (P<0.0001), whereas both fibrinolysis times decreased with TIMI flow (P<0.0001 for both) and TMPG (P<0.01 for both). Multiple regression models showed that only K(s) and fibrinogen were independent predictors of cTFC (P<0.05 for both), TIMI < or = 2 flow (P<0.05 for both) and TMPG-0/1 (P<0.05 for both). CONCLUSIONS: Survivors of myocardial infarction with a history of the no-reflow after PCI are characterized with more compact fibrin network and its resistance to lysis.

[The thrombin generation is associated with the PIA1/A2 beta3, integrin polymorphism in aspirin-treated patients with coronary artery disease: a role of statins]. / Allel PIA1/A2 beta3 integryny wiaze sie ze zwiekszona generacja trombiny u pacjentów z choroba wiencowa leczonych kwasem acetylosalicylowym: wplyw leczenia statynami.

INTRODUCTION: The PIA2 allele is present in about 20-30% of European population. This allele has been associated with resistance to the antithrombotic action of aspirin in healthy PIA2 carriers. OBJECTIVES: To evaluate the functional association of the PIA1/A2 polymorphism of beta3 intergrins with increased thrombin generation and platelet activation in patients with coronary artery disease (CAD), treated with low-dose aspirin and whether the effect of this polymorphism is modulated by statin administration. PATIENTS AND METHODS: In 31 patients (25 M, 6 F) with CAD, aged 47 to 76 years, the thrombin-antithrombin complex generation (TAT) and the soluble form of CD40 ligand level (sCD40L) in blood collected every 60 seconds at sites of standardized microvascular injury were determined. RESULTS: Coronary angiography revealed > or = 1 major epicardial artery stenosis (> or = 50%) in all patients. Genotyping determined 18 subjects homozygous for PIA1 and 13 PIA2 heterozygous carriers. Homozygous PIA1 subjects exhibited increased fibrinogen levels compared with PIA2 carriers (4.2 [IQ 2.39] g/l vs. 2.5 [0.73] g/l, p <0.05). Maximal TAT level observed 6 min after microvascular injury was higher in PIA2 carriers (p = 0.01). Maximal sCD40L did not differ between PIA1/A1 subjects and PIA2 carriers. The PIA2 allele did not alter the velocity of TAT production and sCD40L release. The analysis of the area under the concentration vs. time curve for TAT revealed that PIA2 carriers exhibited increased thrombin generation compared with PIA1A1 subjects (by 17.5%, p <0.05). Subjects treated with statins (n = 12) had lower TAT generation and sCD40L release than non-treated (by 20%, p <0.005 and 23%, p <0.005, respectively). This effect was not altered by the PIA2 presence. CONCLUSIONS: In a model of microvascular injury the PIA1/A2 polymorphism influenced thrombin formation but not platelet activation in CAD patients treated with low-dose aspirin. The PIA2 allele did not alter the beneficial effect of statins on blood coagulation.

[Right ventricular infarction: novel modalities of treatment]. / Zawal miesnia prawej komory serca: nowe sposoby leczenia.

Acute right ventricular infarction (RVI) is usually caused by proximal occlusion of the right coronary artery. RVI is frequent, as it occurs in as many as one out of every two left ventricular interior and/or posterior wall infarctions. The involvement of the right ventricle in acute myocardial infarction has been shown to be associated with an increased risk of life-threatening arrhythmias and sudden cardiac death. Clinical course of RVI can vary from being completely silent to cardiogenic shock (seen in 10-15% patients with inferior wall infarction). RVI diagnosis is based on clinical signs (hypotension and increased jugular venous pressure while pulmonary fields are clear), ECG (ST elevation by > or = 1 mm in V4R), echocardiography (right ventricular wall regional motion abnormalities and/or right ventricle distension, paradoxical motion of the interventricular septum, tissue Doppler), technetium pyrophosphate scanning with ventriculography, and invasive patient monitoring. In addition to its important diagnostic part, the invasive patient monitoring plays a key role in risk stratification and can dynamically guide the treatment (such as fluid loading). In most cases, successful reperfusion in the infarct-related artery territory can be achieved by interventional management (i.e. angioplasty) or--if the latter is not available--by thrombolytic therapy. Patients with arterial hypotension require volume expansion which is best guided by the central venous pressure (CVP; a measure of the right atrial pressure, RAP) and the pulmonary capillary wedge pressure (PCWP). If the hemodynamics does not improve despite optimal fluid loading, pharmacological (catecholamine infusion) or mechanical (intra-aortic balloon pump) circulatory assistance needs to be implemented. Patients with significant sinus bradycardia or 3rd degree AV block may require temporary cardiac pacing. In addition, inhalatory nitric oxide (iNO) has been shown to reduce right ventricular afterload in a selective manner and its potential clinical role is currently being evaluated. Within several months after RVI, the right ventricular performance improves in most patients, including those without successful reperfusion of IRA. Such patients, however, have an increased risk of complications (including sudden death) while the recovery of right ventricular function is slow.