Zbigniew Siudak

Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects

Objective—Homocysteine (Hcy) is a risk factor for thrombosis. We investigated a hypothesis that the clot permeability and its resistance to fibrinolysis is associated with plasma total Hcy (tHcy) in human subjects. Methods and Results—We studied healthy men not taking any medication (n=76), male patients with advanced coronary artery disease (CAD) taking low-dose aspirin (n=33), men with diabetes mellitus diagnosed recently (median hemoglobin A1c 7.65%; n=16), and patients with isolated hypercholesterolemia (>7.0 mmol/L; n=15). We assessed clot permeability and turbidimetric lysis time as the determinants of fibrin clot structure. In a regression model, including age and fibrinogen, plasma tHcy was an independent predictor of clot permeation and fibrinolysis time in healthy subjects (R2=0.88, P<0.0001 and R2=0.54, P<0.0001, respectively). In CAD patients, tHcy and fibrinogen were stronger predictors of the permeation coefficient (R2=0.84; P<0.0001) than was fibrinogen alone (R2=0.66; P<0.0001), whereas tHcy was the only predictor of lysis time (R2=0.69; P<0.0001). Elevated tHcy levels observed after methionine load were not associated with any of the fibrin clot properties. In patients with diabetes or hypercholesterolemia, the influence of Hcy on permeation and, to a lesser extent, on the lysis time was obscured by dominant effects of glucose and cholesterol. In 20 asymptomatic men with hyperhomocysteinemia treated with folic acid, reduction in tHcy levels resulted in increased clot permeability (P=0.0002) and shorter lysis time (P<0.0001). Conclusions—Our results indicate that plasma tHcy predicts clot permeation and susceptibility to fibrinolysis in healthy men and CAD patients. Our data are consistent with a mechanism of thrombosis in hyperhomocysteinemia, which involves modification of fibrinogen by Hcy–thiolactone.

Impact of Multivessel Coronary Artery Disease and Noninfarct-Related Artery Revascularization on Outcome of Patients With ST-Elevation Myocardial Infarction Transferred for Primary Percutaneous Coronary Intervention (from the EUROTRANSFER Registry)

The aim of the study was to assess the impact of multivessel coronary artery disease (MVD) and noninfarct-related artery (non-IRA) revascularization during index percutaneous coronary intervention (PCI) on outcomes of patients with ST-segment elevation myocardial infarction (STEMI). Data on 1,598 of 1,650 patients with complete angiographic data, with >or=1 significantly stenosed epicardial coronary artery, and without previous coronary artery bypass grafting were retrieved from the EUROTRANSFER Registry database. Patients with 1-, 2-, and 3-vessel disease made up 48.5%, 32.0%, and 19.5% of the registry population, respectively. Patients with MVD were less likely to achieve final Thrombolysis In Myocardial Infarction grade 3 flow (1- vs 2- vs 3-vessel disease, 93.6% vs 89.3% vs 87.9%, respectively, p = 0.003) and ST-segment resolution >50% within 60 minutes after PCI (1- vs 2- vs 3-vessel disease, 80.9% vs 77.5% vs 69.3%, respectively, p <0.001). They were also at higher risk of death during 1-year follow-up (1- vs 2- vs 3-vessel disease, 4.9% vs 7.4% vs 13.5%, respectively, p <0.001), and MVD was identified as an independent predictor of 1-year death. In 70 patients (9%) non-IRA PCI was performed during index PCI. These patients were at higher risk of 30-day and 1-year death compared to patients without non-IRA PCI, but this difference in mortality was no longer significant after adjustment for covariates. In conclusion, patients with MVD have decreased epicardial and myocardial reperfusion success and had worse prognosis after primary PCI for STEMI compared to patients with 1-vessel disease. In this large multicenter registry, non-IRA PCI during the index procedure was performed in 9% of patients with MVD and it was associated with increased 1-year mortality.

Thrombus aspiration followed by direct stenting: a novel strategy of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction. Results of the Polish-Italian-Hungarian RAndomized ThrombEctomy Trial (PIHRATE Trial).

BACKGROUND Previous studies with thrombectomy showed different results, mainly due to use of thrombectomy as an additional device not instead of balloon predilatation. The aim of the present study was to assess impact of aspiration thrombectomy followed by direct stenting. METHODS Patients with ST elevation myocardial infarction (STEMI) <6 hours from pain onset and occluded infarct-related artery in baseline angiography were randomized into aspiration thrombectomy followed by direct stenting (TS, n = 100) or standard balloon predilatation followed by stent implantation (n = 96). The primary end point of the study was the electrocardiographic ST-segment elevation resolution >70% (STR > 70%) 60 minutes after primary angioplasty (percutaneous coronary intervention [PCI]). Secondary end points included angiographic myocardial blush grade (MBG) after PCI, combination of STR > 70% immediately after PCI and MBG grade 3 (optimal myocardial reperfusion), Thrombolysis In Myocardial Infarction flow after PCI, angiographic complications, and in-hospital major adverse cardiac events. RESULTS Aspiration thrombectomy success rate was 91% (crossing of the lesion with thrombus reduction and flow restoration). There was no significant difference in STR ≥ 70% after 60 minutes (53.7% vs 35.1%, P = .29). STR > 70% immediately after PCI (41% vs 26%, P < .05), MBG grade 3 (76% vs 58%, P < .03), and optimal myocardial reperfusion (35.1% vs 11.8%, P < .001) were more frequent in TS. There was no difference in between the groups in 6-month mortality (4% vs 3.1%, P = .74) and reinfarction rate (1% vs 3.1%, P = .29). CONCLUSIONS Aspiration thrombectomy and direct stenting is safe and effective in STEMI patients with early presentation (<6 hours). The angiographic parameters of microcirculation reperfusion and ECG ST-segment resolution directly after PCI were significantly better in thrombectomy group despite the lack of the difference in ST-segment resolution 60 minutes after PCI.

Altered Plasma Fibrin Clot Properties Are Associated With In-Stent Thrombosis

Objectives—We sought to investigate whether patients with in-stent thrombosis (IST) display altered plasma fibrin clot properties. Methods and Results—We studied 47 definite IST patients, including 15 with acute, 26 subacute and 6 late IST, and 48 controls matched for demographics, cardiovascular risk factors, concomitant treatment and angiographic/stent parameters. Plasma clot permeability (Ks), which indicates a pore size, turbidity (lag phase, indicating the rate of fibrin clot formation, &Dgr;Absmax, maximum absorbance of a fibrin gel, reflecting the fiber thickness), lysis time (t50%) and maximum rate of d-dimer release from clots (D-Drate) were determined 2 to 73 (median 14.7) months after IST. Patients with IST had 21% lower Ks, 14% higher &Dgr;Absmax, 11% lower D-Drate, 30% longer t50% (all P<0.0001) and 5% shorter lag phase compared to controls (P=0.042). There were no correlations between clot variables and the time of IST or that from IST to blood sampling. Multiple regression analysis showed that Ks (odds ratio=0.36 per 0.1 &mgr;m2, P<0.001), D-Drate (odds ratio=0.16 per 0.01 mg/L/min, P<0.001) and stent length (odds ratio=1.1 per 1 mm, P=0.043) were independent predictors of IST (R2=0.58, P<0.001). Conclusions—IST patients tend to form dense fibrin clots resistant to lysis, and altered plasma fibrin clot features might contribute to the occurrence of IST.

A Prospective, Multicenter Study of a Novel Mesh-Covered Carotid Stent: The CGuard CARENET Trial (Carotid Embolic Protection Using MicroNet).

OBJECTIVES This study sought to evaluate the feasibility of the CGuard Carotid Embolic Protective Stent system-a novel thin strut nitinol stent combined with a polyethylene terephthalate mesh covering designed to prevent embolic events from the target lesion in the treatment of carotid artery lesions in consecutive patients suitable for carotid artery stenting. BACKGROUND The risk of cerebral embolization persists throughout the carotid artery stenting procedure and remains during the stent healing period. METHODS A total of 30 consecutive patients (age 71.6 ± 7.6 years, 63% male) meeting the conventional carotid artery stenting inclusion criteria were enrolled in 4 centers in Germany and Poland. RESULTS The primary combined endpoint was the procedure success of the CGuard system and the number and volume of new lesions on the ipsilateral side assessed by diffusion-weighted magnetic resonance imaging at 48 h post-procedure and at 30 days. The secondary endpoint was 30-day major adverse cardiac or cerebrovascular events (death, stroke, or myocardial infarction). Protection devices were used in all procedures. Procedure success was 100%, with 0% procedural complications. The 30-day major adverse cardiac or cerebrovascular events rate was 0%. New ipsilateral ischemic lesions at 48 h occurred in 37.0% of patients and the average lesion volume was 0.039 ± 0.08 cm(3). The 30-day diffusion-weighted magnetic resonance imaging showed complete resolution of all but 1 periprocedural lesion and only 1 new minor (0.116 cm(3)) lesion in relation to the 48-h scan. CONCLUSIONS The use of the CGuard system in patients undergoing carotid artery stenting is feasible. In addition, the benefit of using CGuard may extend throughout the stent healing period.

Mesh covered stent in ST-segment elevation myocardial infarction

AIMS The MGuard stent (bare metal stent wrapped externally with a polymer mesh sleeve) is designed to prevent distal embolisation by reducing thrombus and plaque fragments released during and post percutaneous coronary intervention (PCI). The aim of this study was to confirm the clinical feasibility, safety and performance of the MGuard stent during primary PCI for ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS The present study was a multicentre, prospective, single arm study in which 60 patients with STEMI <12 hours were enrolled. Predilatation was performed in 61.7% of the cases and thrombus aspiration in 18.3%. In one (1.7%) patient the stent could not cross the lesion. Final TIMI grade 3 flow was observed in 90.0% of patients, with myocardial blush grade 3 in 73.3% of patients and complete (>70%) ST-segment resolution 60 minutes after PCI in 61.4% of patients. In 5.0% of cases distal embolisation occurred. The total major adverse cardiac events rate during the 6-month follow-up was 1.7%. CONCLUSIONS Based on this experience, the MGuard stent implantation in STEMI patients is safe and highly effective. A larger randomised trial is warranted to confirm the clinical endpoints.

Transradial approach in patients with ST-elevation myocardial infarction treated with abciximab results in fewer bleeding complications: data from EUROTRANSFER registry.

ObjectivesOur aim was to investigate the safety and efficacy of transradial approach, predictors of bleeding complications, and choice of radial access site in a real-life setting using a contemporary European registry of percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). BackgroundThere is an increasing amount of data suggesting that transradial approach is associated with less bleeding at access site and other vascular complications when compared with procedures carried out through the femoral artery. MethodsConsecutive data on STEMI patients transferred for primary PCI in hospital STEMI networks between November 2005 and January 2007 from seven countries in Europe were gathered. Patients were divided into the following two groups: radial approach – with radial access site for primary PCI, and transfemoral approach (FEM) – with femoral access site. ResultsData from a total of 1650 patients were collected in the EUROTRANSFER Registry. Abciximab was administered in 1086 patients (66%), 169 patients were assigned to radial approach group, whereas 917 to FEM group. Puncture site hematomas were more frequent in the FEM group (1.2 vs. 9.4%, P<0.001). Major bleedings requiring blood transfusion occurred similarly in both the studied groups. Independent predictors of bleeding (puncture site hematoma and major bleeding requiring transfusion) included female sex, lower weight, chronic renal failure, past stroke, and femoral access site (odds ratio=3.54). ConclusionThe choice of radial access site in patients with STEMI treated with primary PCI is associated with lower local bleeding complications like puncture site hematomas and is an independent predictor of fewer bleedings.

Out-of-hospital cardiac arrest in patients treated with primary PCI for STEMI. Long-term follow up data from EUROTRANSFER registry

OBJECTIVES Our aim was to describe long-term outcome of OHCA patients in a cohort of STEMI patients treated by primary PCI based on the EUROTRANSFER Registry data. BACKGROUND The occurrence of cardiac arrest is associated with impaired survival. There are limited number of studies reporting outcome of STEMI patients with out-of-hospital cardiac arrest (OHCA) treated by primary percutaneous coronary intervention (PCI). The recently published resuscitation guidelines of the European Resuscitation Council (ERC) support immediate angiography/PCI or fibrinolysis in these patients in order to improve survival. METHODS Consecutive data on 1650 STEMI patients, transferred for primary PCI in hospital STEMI networks between November 2005 and January 2007 from 7 countries in Europe were gathered. Patients were divided into two groups: OHCA group - 42 patients and no OHCA group - 1608 patients. RESULTS Baseline demographics, clinical characteristic on admission to cathlab and past medical history were similar in both groups. Cardiogenic shock on admission or acute heart failure defined as Killip 3+4 was more frequently observed in OHCA group. The in-hospital mortality was similar, however, 1-year mortality was 19.1% in the OHCA group vs 8.1% in no OHCA group (p=0.011) and remained significant after exclusion of patients in cardiogenic shock on admission. CONCLUSIONS STEMI patients treated with primary PCI with out-of-hospital cardiac arrest have higher long-term mortality than no OHCA patients. However, resuscitation prior to cathlab admission is not an independent predictor of long-term adverse outcome. No differences in in-hospital mortality were noticed.

More aggressive pharmacological treatment may improve clinical outcome in patients with non-ST-elevation acute coronary syndromes treated conservatively.

IntroductionIncreased adherence to guideline-recommended therapies, especially early invasive strategy introduction may improve clinical outcome in patients with non-ST-elevation acute coronary syndromes. The aim of this study was to assess the impact of more aggressive pharmacological treatment and application of current guidelines in everyday clinical practice in hospitals without on-site invasive facility, with a special focus on its influence on in-hospital mortality in non-ST-elevation acute coronary syndromes patients. MethodsWe identified 807 non-ST-elevation acute coronary syndromes patients treated conservatively in the 29 hospitals participating in the Malopolska Registry of Acute Coronary Syndromes from February to March 2005 and from December 2005 to January 2006. For all patients, pharmacotherapy index based on the use of pharmacological treatment regimen during hospital stay was assessed. Each patient received 1 point for each of the following guideline-recommended drugs used: aspirin, clopidogrel, glycoprotein IIb/IIIa inhibitor, low-molecular-weight heparin, &bgr;-blocker, angiotensin converting enzyme inhibitor/angiotensin II receptor blocker, statin – range of points from 0 to 7. ResultsThe in-hospital mortality decreased with increase of pharmacotherapy index (0 points – 80.0%, 1 point – 36.4%, 2 points – 17.4%, 3 points – 7.6%, 4 points – 5.6%, 5 points – 1.7%, 6 points – 0.0%; P<0.0001, total mortality-5.3%). Independent predictors of in-hospital death were cardiogenic shock, thrombolysis in myocardial infarction (TIMI) risk score, renal insufficiency and pharmacotherapy index. ConclusionsOur findings support the need for more aggressive pharmacological treatment of patients with non-ST-elevation acute coronary syndromes remaining in community hospitals for conservative treatment. Broader implementation of current guidelines and more frequent invasive treatment could improve the outcomes of non-ST-elevation acute coronary syndromes patients.

Impact of direct stenting on outcome of patients with ST‐elevation myocardial infarction transferred for primary percutaneous coronary intervention (from the EUROTRANSFER registry)

We sought to evaluate the impact of direct stenting technique on angiographic and clinical outcomes of patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary angioplasty (PCI).