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Cigarette smokers with ST-segment elevation myocardial infarction (STEMI) may present different response to potent antithrombotic therapy compared to nonsmokers. We assessed the impact of smoking status and intracoronary abciximab in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We pooled data from 5 randomized trials comparing intracoronary versus intravenous abciximab bolus in patients undergoing primary PCI. The primary end point was the composite of death or reinfarction at a mean follow-up of 292 ± 138 days. Of 3,158 participants, 1,369 (43.3%) were smokers, and they had a lower risk of the primary end point in crude, but not in adjusted analyses (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.63 to 1.21, p = 0.405). Intracoronary versus intravenous abciximab was associated with a significant reduction in the risk of primary end point among smokers (3.6% vs 8.0%; HR 0.43, 95% CI 0.26 to 0.72, p = 0.001), but not in nonsmokers (10.2% vs 9.9%; HR 0.99, 95% CI 0.72 to 1.36, p = 0.96), with a significant interaction (p = 0.009). Furthermore, intracoronary abciximab decreased the risk of reinfarction in smokers (HR 0.30, 95% CI 0.15 to 0.62, p = 0.001), with no difference in nonsmokers (HR 1.20, 95% CI 0.71 to 2.01, p = 0.50). Stent thrombosis was lowered by intracoronary abciximab in smokers (HR 0.28, 95% CI 0.06 to 0.66, p = 0.009), but was ineffective in nonsmokers (HR 1.04, 95% CI 0.54 to 2.00, p = 0.903). Interaction testing showed heterogeneity in treatment effect for reinfarction (p = 0.002) and stent thrombosis (p = 0.018) according to smoking status. In conclusion, among patients with STEMI undergoing primary PCI, smoking status did not affect the adjusted risk of clinical events. Intracoronary abciximab bolus improved clinical outcomes by reducing the risk of death or reinfarction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to evaluate clinical outcome for different indications for PCI in an unselected, nationwide PCI population at short- and long-term follow-up., Methods and Results: We evaluated clinical outcome up to six years after PCI in all patients undergoing a PCI procedure for different indications in Sweden between 2006 and 2010. A total of 70,479 patients were treated for stable coronary artery disease (CAD) (21.0%), unstable angina (11.0%), non-ST-elevation myocardial infarction (NSTEMI) (36.6%) and ST-elevation myocardial infarction (STEMI) (31.4%). Mortality was higher in STEMI patients at one year after PCI (9.6%) compared to NSTEMI (4.7%), unstable angina (2.2%) and stable CAD (2.0%). At one year after PCI until the end of follow-up, the adjusted mortality risk (one to six years after PCI) and the risk of myocardial infarction were comparable between NSTEMI and STEMI patients and lower in patients with unstable angina and stable CAD. The adjusted risk of stent thrombosis and heart failure was highest in STEMI patients., Conclusions: The risk of short-term mortality, heart failure and stent thrombosis is highest for STEMI patients after PCI. Therapies to reduce stent thrombosis and heart failure appear to be most important in decreasing mortality in patients with STEMI or NSTEMI undergoing PCI.

Background: Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients., Objectives: To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI)., Methods: Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up., Results: Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26-0.99; p=0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26-1.20; p=0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07-0.99; p=0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n=2574)., Conclusions: In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: To investigate the optimal periprocedural antithrombotic strategy in patients on long-term oral anticoagulation (OAC) who require percutaneous coronary intervention with stenting., Methods and Results: The WOEST study was a randomised controlled trial which recruited 573 patients on long-term OAC who underwent PCI. The periprocedural treatment strategy was left to the operator's discretion. To assess the safety and feasibility of uninterrupted oral anticoagulation (UAC) and bridging therapy (BT), bleeding complications and MACCE were assessed in patients treated according to UAC (n=241) and BT (n=322) regimen. After 30 days, as well as after one year, there were no significant differences in bleeding complications (HR 1.14, 95% CI: 0.77-1.69, p=0.51, and HR 1.26, 95% CI: 0.94-1.69, p=0.12, respectively) and MACCE. MACCE tended to be less frequent in the UAC group (respectively HR 0.48, 95% CI: 0.15-1.51, p=0.21, and HR 0.72, 95% CI: 0.46-1.14, p=0.16). Additionally, adjustment with a propensity score revealed no significant differences. Periprocedural INR was not associated with bleeding or MACCE., Conclusions: In the WOEST study, UAC was not associated with an increase of bleeding or MACCE compared to bridging therapy. This is the largest study up to now to support the current guidelines. The WOEST trial is registered with ClinicalTrials.gov, number NCT00769938.

Aims: Interleukin-6 receptor (IL-6R) signalling has been suggested to play a causal role in the development and outcome of coronary heart disease (CHD). The aim of this study was to investigate the association of sIL-6R levels with myocardial reperfusion after percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI)., Methods: Blood was sampled from 70 patients presenting with STEMI at 6 different time-points (baseline, post-PCI, t=1h, t=6h, t=24h, t=2w). Coronary angiograms post-PCI were analysed for myocardial blush grade (MBG) as indicator of myocardial reperfusion. Serum IL-6 and sIL-6R were measured using IL-6 and sIL-6R enzyme-linked immunosorbent assays (ELISA)., Results: sIL-6R levels fluctuated biphasic during the two weeks after STEMI. Reduced MBG was associated with a larger change in sIL-6R levels between baseline and post-PCI compared to optimal MBG (-13.40; SEM 2.78ng/ml vs -1.99; SEM 2.35ng/ml, respectively; p<0.001). Patients with reduced MBG also showed a larger increase in sIL-6R levels after PCI and 1h after myocardial infarction (MI) compared to optimal MBG (respectively 11.56; SEM 2.68ng/ml vs 3.02; SEM 2.39ng/ml; p=0.018). IL-6/sIL-6R ratio was also more increased in patients with reduced MBG at 24h after myocardial infarction (0.23; SEM 0.08-0.51 vs 0.10; SEM 0.05-0.21; p=0.024). An optimal MBG was associated with a 10ng increase in sIL-6R level between baseline and post-PCI (OR 1.687, CI 1.095-2.598; p=0.018)., Conclusions: sIL-6R levels fluctuate biphasic during the two weeks after MI with larger changes and increased IL-6/sIL-6R ratio in patients with reduced MBG. Further research is needed to increase our understanding of the possible causality of these associations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Several studies have highlighted the prognostic role of preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) in patients with ST-segment elevation myocardial infarction (STEMI). However, the impact of preprocedural IRA occlusion in patients with diabetes with STEMI has been insufficiently studied. The aim of this study was to evaluate the effects of baseline IRA occlusion and diabetic status in patients with STEMI who underwent primary percutaneous coronary intervention by using data from a pooled analysis of randomized trials comparing intracoronary with intravenous abciximab bolus administration. A total of 3,046 patients with STEMI who underwent primary percutaneous coronary intervention were included. Diabetes was present in 578 patients (19%). The primary outcome was mortality after a median follow-up period of 375 days. Secondary end points were reinfarction and stent thrombosis. In patients without diabetes, IRA occlusion versus no occlusion was not associated with increased rates of mortality (4.3% vs 2.7%, p = 0.051) and reinfarction (3.3% vs 2.5%, p = 0.33). Patients with diabetes with IRA occlusion compared with those without occlusion showed higher rates of mortality (10.6% vs 4.6%, p = 0.01) and reinfarction (5.6% vs 2.1%, p = 0.03). Baseline IRA occlusion increased the rate of stent thrombosis in the nondiabetic (2.1% vs 1.0%, p = 0.04) and diabetic (3.2% vs 0.8%, p = 0.05) cohorts. Interaction analysis demonstrated that the risk for death and reinfarction was significantly increased when diabetes and IRA occlusion occurred concomitantly. In conclusion, patients with STEMI with diabetes and baseline IRA occlusion had disproportionately higher rates of death and reinfarction. Preprocedural IRA occlusion increased the risk for stent thrombosis, irrespective of diabetic status., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Importance: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function., Objective: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI)., Design, Setting, and Participants: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013., Interventions: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months., Main Outcomes and Measures: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure., Results: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed., Conclusions and Relevance: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting., Trial Registration: clinicaltrials.gov Identifier: NCT01217307.

Aims: In recent years, intracoronary bolus abciximab has emerged as an alternative to the standard intravenous route in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The aim of the current study was to perform an individual patient-level pooled analysis of randomised trials, comparing intracoronary versus intravenous abciximab bolus use in STEMI patients undergoing primary PCI., Methods and Results: Individual data of 3,158 patients enrolled in five trials were analysed. Reperfusion endpoints were: post-procedural Thrombolysis in Myocardial Infarction (TIMI) 3 flow, myocardial blush grade (MBG) 2/3 and complete ST-segment resolution. The primary clinical endpoint of interest was the composite of death and reinfarction at 30 days. Compared with the intravenous route, intracoronary abciximab bolus administration did not improve TIMI 3 flow (odds ratio [OR] 1.19; 95% confidence interval [CI]: 0.90-1.59; p=0.23) and complete ST-segment resolution (OR 1.22, 95% CI: 0.92-1.63, p=0.17), but increased MBG 2/3 occurrence (OR 1.83, 95% CI: 1.05-3.18, p=0.03). At 30-day follow-up, intracoronary bolus abciximab did not reduce the risk of death and reinfarction (OR 0.78, 95% CI: 0.55-1.10, p=0.16), death (OR 0.77, 95% CI: 0.51-1.17, p=0.22), reinfarction (OR 0.79, 95% CI: 0.46-1.33, p=0.38) and stent thrombosis (OR 0.77, 95% CI: 0.43-1.35, p=0.36) as compared with intravenous administration., Conclusions: In STEMI patients undergoing primary PCI, intracoronary abciximab does not provide additional benefits as compared with standard intravenous treatment and, therefore, it should not be recommended as the default route of administration in this setting.

Multiple biomarkers improve prognostication for long-term mortality in ST-segment elevation myocardial infarction (STEMI). However, one-third of mortality after STEMI occurs within initial discharge. Our objective was to determine whether multiple biomarkers (glucose, N-terminal pro-brain natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR)) predict both short-term as long-term mortality in STEMI. We used a patient-pooled dataset of consecutive STEMI patients, with complete biomarkers, who underwent primary percutaneous coronary intervention (PCI) in two single centers (Amsterdam and Groningen). With a previously developed multimarker risk score, based on three biomarkers, patients were indicated as low-, intermediate- or high risk. Cumulative 4-year mortality was estimated with the Kaplan-Meier method and compared with a log-rank test. We compared short-term and long-term mortality with a landmark set at 30 days because previous studies have shown that mortality largely occurs within 30 days. A total of 2,355 STEMI-patients were treated with primary PCI. The mortality rates in the low- (n = 1,531), intermediate- (n = 403) and high-risk (n = 421) groups were 4.8, 16.1, and 43.9 %, respectively. The differences were observed at a follow-up up to 30 days (log-rank p < 0.001) as well as after 30 days (log-rank p < 0.001). A multimarker risk score, based on admission levels of glucose, NT-proBNP, and eGFR identifies STEMI patients at low-, intermediate-, and high-risk for short-term and long-term mortality.

Background: For patients with ST-elevation myocardial infarction (STEMI), guidelines recommend prehospital triage and direct referral to a percutaneous coronary intervention (PCI)-capable centre in order to minimize ischemic time. However, few have studied failed prehospital diagnosis. We assessed the incidence, predictors, and clinical impact of interhospital transfer for primary PCI after initial referral to a non-PCI-capable centre due to a failed prehospital STEMI diagnosis., Methods: We studied 846 consecutive STEMI patients undergoing primary PCI between January 2008 and January 2010., Results: We found that 609 patients (72%) were directly admitted through prehospital triage and 127 patients (15%) required interhospital transfer after failed prehospital diagnosis. Median first medical contact to treatment time was 88 min in the prehospital diagnosis group and 155 min in the interhospital transfer group (p<0.001). In the interhospital transfer group, the first available electrocardiogram was diagnostic for STEMI in 77% of cases. Predictors of interhospital transfer were female gender, diabetes, prior myocardial infarction, and greater event location to PCI-capable centre distance. Interhospital transfer independently accounted for a 47% increase in ischemic time (95% CI 33 to 63%; p<0.001). One-year mortality was higher in the interhospital transfer group (10 vs. 5.3%; p=0.030)., Conclusions: Despite an often-diagnostic electrocardiogram, interhospital transfer after failed prehospital diagnosis occurred in 15% of STEMI patients undergoing primary PCI. Interhospital transfer was a major predictor of ischemic time and 1-year mortality was significantly higher. Continuing efforts to optimize prehospital triage are warranted, especially among patients at higher risk of failed prehospital diagnosis.

Background: If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin., Methods: We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938., Findings: 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26-0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17-0·84, p=0·011)., Interpretation: Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events., Funding: Antonius Ziekenhuis Foundation, Strect Foundation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to describe the characteristics and outcome of all consecutive patients treated with percutaneous coronary intervention (PCI) in an unselected nationwide cohort over the past 2 decades., Background: Over the last 20 years, treatment with PCI has evolved dramatically, but the change in patient characteristics has not been well described., Methods: We included all patients undergoing a PCI procedure for the first time between January 1990 and December 2010 from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Patients were divided into different cohorts on the basis of the year of the first PCI procedure., Results: A total of 144,039 patients was included. The mean age increased from 60.1 ± 9.9 years in 1990 to 1995 to 67.1 ± 11.2 years in 2009 to 2010. The proportion of patients presenting with unstable coronary artery disease and ST-segment elevation myocardial infarction increased from 27.4% and 6.2% to 47.7% and 32.5%, respectively. Diabetes mellitus and multivessel disease were more often present in the later-year cohorts. The 1-year mortality increased from 2.2% in 1990 to 1995 to 5.9% in 2009 to 2010, but after adjustment for age and indication, a modest decrease was shown, mainly in ST-segment elevation myocardial infarction patients., Conclusions: Characteristics of PCI patients have changed substantially over time, reflecting the establishment of new evidence. The increasing age and proportion of patients undergoing PCI for acute coronary syndromes greatly influence outcome. Understanding the changing patient characteristics is important for the translation of evidence to real-world clinical practice.

Over the past few years transcatheter heart valve implantation (THI) has become an alternative treatment for aortic valve replacement. The THI does not require a midline sternotomy or cardiopulmonary bypass and can be performed through a transfemoral or a transapical approach. In case of severe peripheral vascular disease the transapical route is usually chosen. However, when the use of a small anterolateral thoracotomy is not preferred due to comorbidities, the subclavian artery can be considered as a third alternative route. This case report describes an approach for THI through the subclavian artery, by using a Dacron graft., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular dysfunction and the development of heart failure is a frequent and serious complication of myocardial infarction. Recent animal experimental studies suggested that metformin treatment reduces myocardial injury and preserves cardiac function in non-diabetic rats after experimental myocardial infarction. We will study the efficacy of metformin with the aim to preserve left ventricular ejection fraction in non-diabetic patients presenting with ST elevation myocardial infarction (STEMI)., Methods: The Glycometabolic Intervention as adjunct to Primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial is a prospective, single center, double blind, randomized, placebo-controlled trial. Three-hundred-and-fifty patients, without diabetes, requiring primary percutaneous coronary intervention (PCI) for STEMI will be randomized to metformin 500 mg twice daily or placebo treatment and will undergo magnetic resonance imaging (MRI) after 4 months. Major exclusion criteria were prior myocardial infarction and severe renal dysfunction. The primary efficacy parameter is left ventricular ejection fraction 4 months after randomization. Secondary and tertiary efficacy parameters include major adverse cardiac events, new onset diabetes and glycometabolic parameters, and echocardiographic diastolic function. Safety parameters include renal function deterioration and lactic acidosis., Conclusions: The GIPS-III trial will evaluate the efficacy of metformin treatment to preserve left ventricular ejection fraction in STEMI patients without diabetes.

TLR (Toll-like receptor) activation-induced inflammatory responses are important in the progression of atherosclerosis. We previously showed that TLR-dependent leucocyte responsiveness is acutely attenuated following percutaneous coronary intervention or vascular surgery. Furthermore, cytokine release following whole-blood TLR-2 and TLR-4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischaemia can elicit an enhanced inflammatory response. In the present study, we assessed the association between leucocyte TLR-2 and TLR-4 responsiveness and pre-existent and inducible ischaemia in patients undergoing SPECT (single-photon emission computed tomography)-MPI (myocardial perfusion imaging). TLR-2, TLR-4 and CD11b expression on monocytes were measured in blood samples that were obtained from 100 patients with suspected coronary artery disease before and after myocardial stress testing for SPECT-MPI. IL-8 (interleukin-8) levels were determined after whole-blood stimulation with Pam3Cys (TLR-2) and LPS (lipopolysaccharide; TLR-4). On the basis of SPECT-MPI, patients were categorized into three groups: reversible defect, irreversible defect and no defect. Myocardial stress induced a reduction in TLR-4 expression (2.46±0.21 compared with 2.17±0.16 arbitrary units, P=0.001) and CD11b expression (83.2±1.73 compared with 76.0±1.89 arbitrary units, P<0.001). TLR-induced IL-8 production before myocardial stress induction was not associated with the results of SPECT-MPI. However, a significant decrease in IL-8 production following TLR stimulation was observed after stress, which was more pronounced in patients with a reversible defect. In conclusion, inducible ischaemia is associated with a decrease in whole-blood TLR-2 and TLR-4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischaemia.

Objectives: The aim of this study was to perform an individual patient-level pooled analysis of randomised trials, comparing intracoronary versus intravenous abciximab bolus use in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)., Background: Abciximab represents a cornerstone in the treatment of STEMI patients undergoing primary PCI. Intracoronary abciximab bolus administration has been proposed as an alternative strategy to the standard intravenous route. However, whether intracoronary abciximab effectively improves clinical outcomes compared with standard route remains unknown., Methods: Individual data of 1198 patients enrolled in five trials were entered into the pooled analysis. The primary endpoint of the study was the occurrence of all-cause death and reinfarction at 30-day follow-up. Secondary endpoints were all-cause death, reinfarction and target-vessel revascularisation (TVR)., Results: No significant heterogeneity was found across trials. Compared with the intravenous route, intracoronary abciximab administration significantly reduced the risk of the composite of death and reinfarction (HR 0.52, 95% CI 0.29 to 0.94; p=0.03), death (HR 0.44, 95% CI 0.20 to 0.95; p=0.04) and TVR (HR 0.53, 95% CI 0.29 to 0.99; p=0.045), without a significant impact on the risk of reinfarction (HR 0.54, 95% CI 0.24 to 1.21; p=0.13). However, after correction for baseline differences, only the composite of death/reinfarction and death remained significant., Conclusions: In STEMI patients undergoing primary PCI, intracoronary abciximab administration, when compared with the intravenous standard route, can improve short-term clinical outcomes mainly by reducing the risk of death.

Current treatment for coronary stent thrombosis (ST) often lacks satisfactory results and clinical outcome is poor. We investigated the impact of manual thrombus aspiration during percutaneous coronary intervention (PCI) on myocardial reperfusion and clinical outcome in patients with angiographically proved ST. We interrogated our PCI registry for patients with a first stent placement from January 2002 through May 2010 who had undergone an emergency repeated PCI procedure and systematically reviewed coronary angiograms and hospital records for evidence of ST. We identified 113 patients with ST. Thrombus aspiration was used in 51 patients and 62 patients received conventional PCI. Histopathologic analysis of thrombus aspirates was performed in 6 patients. Use of thrombus aspiration predicted postprocedure Thrombolysis In Myocardial Infarction grade 3 flow (odds ratio 3.16, 95% confidence interval 1.22 to 8.17, p = 0.018) and myocardial blush grade 2/3 (odds ratio 3.20, 95% confidence interval 1.20 to 8.55, p = 0.020) after multivariable adjustment with bootstrap model selection. Distal embolization was lower in the thrombus aspiration group compared to the conventional PCI group (14% vs 37%, p = 0.017). In most patients, aspirated thrombus was large and contained platelet and erythrocyte components at histopathologic analysis. Mortality in the thrombus aspiration group and conventional PCI group was 9.8% versus 16% at 30 days (p = 0.351) and 12% versus 21% at 1 year (p = 0.220), respectively. In conclusion, use of manual thrombus aspiration in patients with ST was associated with greater epicardial and microvascular myocardial reperfusion. In addition, mortality was lower in patients treated with thrombus aspiration, although not statistically significant., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Early reperfusion of the infarct-related coronary artery is an important issue in improvement of outcomes after ST-segment elevation myocardial infarction (STEMI). In this study, the clinical significance of total ischemic time on myocardial reperfusion and clinical outcomes was evaluated in patients with STEMI treated with primary percutaneous coronary intervention and thrombus aspiration and additional triple-antiplatelet therapy. Total ischemic time was defined as time from symptom onset to first intracoronary therapy (first balloon inflation or thrombus aspiration). All patients with STEMI treated with primary percutaneous coronary intervention with total ischemic times ≥30 minutes and <24 hours from 2005 to 2008 were selected. Ischemic times were available in 1,383 patients, of whom 18.4% presented with total ischemic times ≤2 hours, 31.2% >2 to 3 hours, 26.8% >3 to 5 hours, and 23.5% >5 hours. Increased ischemic time was associated with age, female gender, hypertension, and diabetes. Patients with total ischemic times <5 hours more often had myocardial blush grade 3 (40% to 45% vs 22%, p <0.001) and complete ST-segment resolution (55% to 60% vs 42%, p = 0.002) than their counterparts with total ischemic times >5 hours. In addition, patients with total ischemic times ≤5 hours had lower 30-day mortality (1.5% vs 4.0%, p = 0.032) than patients with total ischemic times >5 hours. In conclusion, in this contemporary cohort of patients with STEMI treated with primary percutaneous coronary intervention, triple-antiplatelet therapy, and thrombus aspiration, short ischemic time was associated with better myocardial reperfusion and decreased mortality. After a 5-hour period in which outcomes remain relatively stable, myocardial reperfusion becomes suboptimal and mortality increases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Early detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI., Methods: We included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12 h of symptom onset. Blood samples were taken on admission and at four time points within the first 24 h after PCI., Results: In contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249 pmol/L and normalized within 10 h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14 h from symptom onset at a maximum of 275 U/L, 5.75 μg/L, and 4.16 μg/L, respectively, and decreased more gradually., Conclusions: Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.

Objective: Shorter leukocyte telomeres are associated with atherosclerosis and predict future heart disease. The goal of the present study was to determine whether leukocyte telomere length is related to atherosclerotic plaque telomere length and whether it is associated with plaque characteristics or recurrence of disease., Methods and Results: Telomere length was measured by real-time quantitative polymerase chain reaction in atherosclerotic plaques and leukocytes in patients with carotid atherosclerosis undergoing carotid endarterectomy (n=684) and of leukocytes in age- and gender-balanced subjects without clinical atherosclerosis (n=780). Leukocyte telomere length was shorter in patients versus controls (0.99 [interquartile range (IQR): 0.79 to 1.26] versus 1.06 [0.80 to 1.39]; P=0.0007). Plaque telomeres were longer than leukocyte telomeres (1.42 [IQR: 1.21 to 1.77] versus 1.01 [IQR: 0.75 to 1.34]; P<1.00×10(-6)) and independent of age. Leukocyte and plaque telomere length were only weakly correlated (correlation coefficient r2=0.04, P=0.03). Patients, whose plaques showed marked macrophage infiltration and large lipid core, had longer plaque telomeres (1.61 [IQR: 1.32 to 2.04] versus 1.40 [IQR: 1.15 to 1.57]; P=0.006) and shorter leukocyte telomeres (0.88 [IQR: 0.75 to 1.20] versus 1.03 [IQR: 0.83 to 1.34]; P=0.02). Plaque telomere length was associated with restenosis 1 year after endarterectomy (OR 1.58±0.206; P=0.026 per SD decrease of plaque telomere length)., Conclusions: Leukocyte telomere length is associated with the presence of atherosclerotic carotid plaques but is not a proxy for local plaque telomere length. Plaque telomere length is related to plaque characteristics and development of restenosis following endarterectomy.

Objectives: This study evaluated the impact of a chronic total occlusion (CTO) in a non-infarct related coronary artery (IRA) on markers of reperfusion, infarct size, and long-term cardiac mortality in patients with ST-elevation myocardial infarction (STEMI)., Background: A concurrent CTO in STEMI patients has been associated with impaired left ventricular function and outcome. However, the impact on markers of reperfusion is unknown., Methods: All 1,071 STEMI patients included in the TAPAS-trial between January 2005 and December 2006 were used for this substudy. Endpoints were the association between a CTO in a non-IRA and myocardial blush grade (MBG) of the IRA, ST-segment elevation resolution (STR), enzymatic infarct size, and clinical outcome., Results: A total of 90 patients (8.4%) had a CTO. MBG 0 or 1 occurred more often in the CTO group (34.2% versus 20.6% (Odds Ratio [OR] 2.00, 95% confidence interval [CI]: 1.22-3.23, P = 0.006)). Incomplete STR occurred more often in the CTO group, (63.6% versus 48.2% [OR 1.96, 95% CI: 1.22-3.13, P = 0.005]). Median level of maximal myocardial-band of creatinin kinase (CK-MB) in the CTO group was 75 μg/l (IQR 28-136) and 51 μg/l (IQR 18-97) in the no-CTO group (P = 0.021). The presence of a CTO in a non-IRA in STEMI patients was an independent risk factor for cardiac mortality (HR 2.41, 95% CI: 1.26-4.61, P = 0.008) at 25 months follow-up., Conclusion: A CTO in a non-IRA is associated with impaired reperfusion markers and impaired long-term outcome in STEMI patients., (Copyright © 2010 Wiley-Liss, Inc.)

Sudden cardiac death (SCD) remains a major health issue accounting for over 5% of annual mortality in the Western world. There are several causes of SCD, most commonly, coronary artery disease. Although identifying the prodrome of SCD has attracted considerable interest, a large proportion of patients die before any medical contact is established. SCD onset seems to follow a circadian pattern, most likely because of exposure to endogenous and exogenous triggers. The aim of the present report is to review the current knowledge of epidemiology, patterns of onset, and triggers of SCD and present directions for future research with a focus on coronary artery disease., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Aims: Primary percutaneous coronary intervention (PCI) is a widely practised therapeutic procedure to treat ST-elevation myocardial infarction (STEMI). However, a significant proportion of patients undergoing primary PCI suffers from adverse events, such as incomplete myocardial reperfusion. It is currently unknown to which degree these adverse events are operator related., Methods and Results: We investigated inter-operator variation using objective safety and efficacy endpoints during primary PCI for STEMI. All PCIs were performed by six experienced interventional cardiologists as part of a randomised single centre trial. The primary endpoint of this study was optimal myocardial reperfusion (myocardial blush grade 3 [MBG]). All 1,071 patients enrolled in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) were included in this analysis. In the six operator groups, the rate of the primary endpoint MBG 3 ranged between 29.2% and 55.5%. The variable for operators remained significantly associated with MBG 3 after adjustment for baseline and procedural differences. There were no statistical differences observed with regard to safety endpoints., Conclusions: This study illustrates the observation that even in a controlled setting significant inter-operator variation may exist in the efficacy of primary PCI. This study supports the routine collection of high-quality datasets to evaluate and improve individual operator competence and skills.

Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months) spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP) rats (n = 6-7 in each group). Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA(1c) levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities.

Background: Multiple trials have documented that myocardial blush grade (MBG) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) has prognostic value for long-term clinical outcome. However, to the best of our knowledge, no study has determined the clinical use of MBG in routine clinical practice. We determined the prognostic value of MBG scored by the operator during primary PCI in consecutive patients with STEMI., Methods and Results: The prognostic value of MBG scored by the operator in relation to 1-year all cause mortality was evaluated in all patients with STEMI who underwent primary PCI between January 2004 and July 2008 in our hospital. The incidence of MBG 0, 1, 2, and 3 was 12%, 14%, 36%, and 38%, respectively, in 2118 consecutive patients with STEMI. Follow-up of all 2118 patients showed a 1-year all cause mortality rate of 8% (168 of 2118): 24%, 10%, 6%, and 4%, respectively, among patients with MBG 0, 1, 2, and 3 (P<0.001). In the 1763 patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after PCI, these mortality rates were 17%, 10%, 6%, and 4%, respectively (P<0.001). MBG scored by the operator was a strong independent predictor of 1-year all cause mortality corrected for other well-known predictive variables, including TIMI flow grade., Conclusions: MBG scored by the operator during primary PCI has prognostic value for 1-year all cause mortality in patients with STEMI in routine clinical practice. Therefore, the MBG should be documented, in addition to the TIMI flow grade, during primary PCI in patients with STEMI in standard PCI reports in routine clinical practice.

Background: Administration of abciximab during primary percutaneous coronary intervention is an effective adjunctive therapy in the treatment of patients with ST-segment elevation myocardial infarction. Recent small-scaled studies have suggested that intracoronary administration of abciximab during primary percutaneous coronary intervention is superior to conventional intravenous administration. This study has been designed to investigate whether intracoronary bolus administration of abciximab is more effective than intravenous bolus administration in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration., Methods/design: The Comparison of IntraCoronary versus intravenous abciximab administration during Emergency Reperfusion Of ST-segment elevation myocardial infarction (CICERO) trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 530 patients with STEMI undergoing primary percutaneous coronary intervention are randomly assigned to either an intracoronary or intravenous bolus of weight-adjusted abciximab. The primary end point is the incidence of >70% ST-segment elevation resolution. Secondary end points consist of post-procedural residual ST-segment deviation, myocardial blush grade, distal embolization, enzymatic infarct size, in-hospital bleeding, and clinical outcome at 30 days and 1 year., Discussion: The CICERO trial is the first clinical trial to date to verify the effect of intracoronary versus intravenous administration of abciximab on myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration.

Background: Coronary microvascular dysfunction is frequently seen in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. Previous studies have suggested that the administration of intravenous adenosine resulted in an improvement of myocardial perfusion and a reduction in infarct size. Intracoronary adenosine (bolus of 30 to 60 microg) is a guideline-recommended therapy to improve myocardial reperfusion. The effect of intracoronary adenosine during primary percutaneous coronary intervention has not been investigated in a large randomized trial., Methods and Results: Patients presenting with acute ST-elevation myocardial infarction were randomized to 2 bolus injections of intracoronary adenosine (2 x 120 microg in 20 mL NaCl) or placebo (2 x 20 mL NaCl). The first bolus injection was given after thrombus aspiration and the second after stenting of the infarct-related artery. The primary end point was the incidence of residual ST-segment deviation <0.2 mV, 30 to 60 minutes after percutaneous coronary intervention. Secondary end points were ST-segment elevation resolution, myocardial blush grade, Thrombolysis in Myocardial Infarction flow on the angiogram after percutaneous coronary intervention, enzymatic infarct size, and clinical outcome at 30 days. A total of 448 patients were randomized to intracoronary adenosine (N=226) or placebo (N=222). The incidence of residual ST-segment deviation <0.2 mV did not differ between patients randomized to adenosine or placebo (46.2% versus 52.2%, P=NS). In addition, there were no significant differences in secondary outcome measures., Conclusions: In this randomized placebo controlled trial enrolling 448 patients with ST-elevation myocardial infarction, administration of intracoronary adenosine after thrombus aspiration and after stenting of the infarct-related artery did not result in improved myocardial perfusion.

Aims: To evaluate non-invasive angiography using dual-source computed tomography (CT) for the determination of the most appropriate therapeutic strategy in patients with suspected coronary artery disease (CAD)., Methods and Results: CT angiography (Dual Source CT, Somatom Definition, Siemens Medical Systems, Forchheim, Germany) was performed in 60 consecutive patients [51 men, median age 64 (57-70) years] scheduled for elective coronary angiography. Both techniques were used to evaluate the presence of CAD, significant stenosis, and the need for revascularization therapy. Sensitivity and specificity for the presence of significant stenosis were: per segment (n = 766) 62% (95% CI 50-72) (64/104) and 79% (95% CI 74-84) (526/662), respectively; per patient (n = 60) 100% (95% CI 91-100) (38/38) and 45% (95% CI 24-68) (10/22), respectively. In therapeutic decision-making based on CT angiography, sensitivity, specificity, positive and negative predictive values for intervention were 97% (95% CI 84-100) (36/37), 48% (95% CI 27-69) (11/23), 75% (95% CI 60-86) (36/48), and 92% (95% CI 60-100) (11/12), respectively. If a revascularization procedure was needed, the CT angiographic data indicated the appropriate modality (percutaneous coronary intervention or coronary artery bypass grafting) in 70% (26/36) of patients., Conclusion: Although imaging qualities have improved considerably, CT angiography cannot be used for definitive therapeutic decision-making with regard to revascularization procedures in patients with suspected CAD.

Objectives: To investigate the feasibility and safety of manual thrombus aspiration in patients undergoing percutaneous coronary intervention (PCI) for non-ST-elevation myocardial infarction (NSTEMI)., Background: Myocardial necrosis in patients with acute coronary syndromes may be a sign of microvascular obstruction, owing to spontaneous or PCI-induced embolization of atherothrombotic material. Manual thrombus aspiration results in improved myocardial reperfusion in patients undergoing PCI for ST-elevation myocardial infarction. Currently, no published data on thrombus aspiration in patients with NSTEMI are available., Methods: As part of a prospective cohort study, 70 patients undergoing PCI for NSTEMI were treated with thrombus aspiration (Export Aspiration Catheter, Medtronic, Minneapolis, MN). Histopathological analysis was performed on aspirated material., Results: Thrombus aspiration was effective in 58 patients (83%) and resulted in a marked reduction of TIMI-thrombus score 4/5 (40% pre- versus 7% postthrombus aspiration) and increase of the rate of TIMI-flow 3 (36% pre- versus 66% postthrombus aspiration). The incidence of myocardial blush grade 2 and 3 were 39 and 45%, respectively. Distal embolization was visible in three patients (4%) on the final angiogram., Conclusion: This study demonstrates that thrombus aspiration in most NSTEMI patients is feasible and safe and is associated with a high rate of retrieval of thrombotic material., (Copyright 2008 Wiley-Liss, Inc.)

Background: The main goal of the initial treatment of ST-segment elevation myocardial infarction is prompt reperfusion of the infarct-related artery. The value of pretreatment with clopidogrel before primary percutaneous coronary intervention is currently unclear., Methods and Results: Studies were retrieved through MEDLINE and Cochrane Controlled Trials Register searches over the past 20 years. Two authors independently performed the study selection and data extraction. Randomized controlled studies were included when the research subjects were unselected patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Pilot trials, studies that enrolled patients undergoing rescue percutaneous coronary intervention, and studies with angiographic assessment not performed by a core laboratory or 2 blinded investigators were excluded. Thirty-eight treatment groups, including 8429 patients, were included. Initial patency was higher in treatment groups in which patients received pretreatment with clopidogrel (34.3%; 95% confidence interval, 32.9 to 35.8) compared with those in which patients did not receive clopidogrel before initial coronary angiography (25.8%; 95% confidence interval, 24.5 to 27.1). In multivariate-weighted logistic regression analysis, pretreatment with clopidogrel was an independent predictor of early reperfusion (odds ratio, 1.51; 95% confidence interval, 1.31 to 1.74; P<0.0001) and improved clinical outcome., Conclusions: Initial patency and clinical outcome were improved in treatment groups that received pretreatment with clopidogrel. These results in patients undergoing primary percutaneous coronary intervention are in line with the experience of pretreatment with clopidogrel in elective patients, non-ST-elevation coronary syndromes, and thrombolytic studies.

Purpose: To explore the hypothesis that stent placement decreases dilator function of various arteries outside the stented segment and that angiotensin- (1-7) improves this function, and to assess the contribution of dilator signal compounds. A further objective was to test the hypothesis that on-stent delivery of Ang-(1-7) reduces neointima formation and improves endothelial function., Methods: Abdominal aortic stenting or sham operation was performed in the rat four weeks after stenting and treatment with intravenous saline or Ang-(1-7) infusion (24 mug/kg/h); vasomotor function in isolated thoracic aorta and brachial and iliac artery was measured in organ baths. Furthermore, Ang-(1-7)-eluting stents were designed and placed in rat abdominal aorta. Neointima formation and aortic function were tested after four weeks., Results: Relaxation of the thoracic aorta to metacholine was decreased after stenting compared with shams due to a decrease in nitric oxide-mediated response (67% reduction in maximal NO-dependent response). Ang-(1-7) restored the response mainly through increased prostaglandin- and possibly also endothelial-derived hyperpolarising factor-mediated relaxation. Relaxation in the brachial artery decreased after stenting (maximal response dropped by 50%), whilst contractions to phenylephrine increased. Ang-(1-7) normalised vasomotor function. Iliac artery function remained unaltered after stenting but Ang-(1-7) increased maximal relaxations by 65%. Delivery of Ang-(1-7) by means of a drug-eluting stent improved endothelial function., Conclusion: Stenting differentially affects dilator and contractile function in various arterial beds. Ang-(1-7) both improves dilator function and normalises contractile function. Delivery of protective peptides such as Ang-(1-7) from the stent is a new therapy option that merits further development and exploration. (Neth Heart J 2008;16:293-8.).

Objectives: The objective of this study was to compare 2 manual thrombus aspiration catheters in unselected patients with ST-segment elevation myocardial infarction., Background: Distal embolization is common during percutaneous coronary intervention in ST-segment elevation myocardial infarction and can induce impaired myocardial perfusion. Several aspiration thrombectomy devices have been introduced to prevent distal embolization, however, with conflicting clinical results. Currently, it is unclear to what extent this variance in outcome can be explained by device-related factors, such as internal lumen size., Methods: We performed a prospective cohort study in which patients undergoing primary percutaneous coronary intervention were treated with a large-internal-lumen catheter (Diver, Invatec, Roncadelle, Italy). Outcomes were compared with a matched population of the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) trial, in which patients were treated with a medium-sized catheter (Export, Medtronic, Minneapolis, Minnesota). A histopathological analysis was performed of retrieved material., Results: A total of 160 patients, treated with the Diver (n = 80) or Export (n = 80) aspiration catheter, were enrolled. Effective thrombus aspiration was seen in 70.3% of the patients treated with the Diver catheter versus 81.8% with the Export catheter (p = 0.10) No significant difference was found in myocardial blush grade or electrocardiographic outcome between the 2 devices. Size distribution of retrieved thrombotic particles was similar per device. Erythrocyte-rich thrombi were found in 34.8% of the cases and were predominately seen in patients with low initial Thrombolysis In Myocardial Infarction flow grade (p = 0.008)., Conclusions: A larger internal lumen diameter does not result in retrieval of larger thrombotic particles, nor in improved angiographic or electrocardiographic outcomes.

Background: To evaluate the effect of supraphysiological levels of angiotensin II and selective angiotensin II type 1 receptor (AT1-receptor) blockade on neointimal formation and systemic endothelial function after stent implantation in the rat abdominal aorta., Methods: Male Wistar rats were randomized to one of three groups; control (n=8), angiotensin II infusion (n=9, 200 ng/kg/min), or candesartan cilexetil (n=8,AT1-receptor blocker; rats received 14.4 mg kg(-1) day(-1)). Stents were implanted in the abdominal aorta. Histological analyses were performed at 4 weeks. Endothelial function was determined in isolated thoracic aortic rings., Results: Neointimal area was increased in the angiotensin II treated group versus the control group, 0.88 mm(2)+/-0.21 versus 0.66 mm(2)+/-0.16 (P<0.05). Neointimal thickness was 171 microm+/-44 in angiotensin II treated animals and 120 microm+/-25 in the control group (P<0.05). In addition, endothelial function was attenuated in angiotensin II treated animals (P=0.01). Candesartan cilexetil treatment did not result in reduction of neointimal area and did not reduce neointimal thickness compared to the control group. Candesartan had no effect on endothelial function., Conclusions: Supraphysiological levels of angiotensin II aggravates neointimal formation in the stented rat abdominal aorta, and in parallel decreases endothelial function. AT1-receptor blockade does not reduce neointimal formation in rats without supraphysiological angiotensin II levels.

Objectives: To compare Angio-Seal (AS) and StarClose (SC) and manual compression (MC) on efficacy of hemostasis, complication rate, safety of early mobilization, and patient comfort., Background: Closure of the femoral artery after cardiac catheterization can be obtained through different methods. Today, physicians can choose from a number of different devices to achieve arterial closure., Methods: In a prospective trial 450 patients were randomized to AS, SC, or MC. Patients were mobilized 1 to 2 hr after device placement, and 6 hr after MC. Data were collected during hospital admission and by telephone at one month after hospital discharge., Results: Devices were used in 138/150 allocated to AS and 124/150 allocated to SC patients (92% vs. 83%, P = 0.015) Patients with MC experienced more pain during sheath removal than patients receiving a device, and rated their period of bed rest as less comfortable. Oozing and need for pressure bandage at the puncture site were observed in 37 AS patients and 57 SC patients (25% vs. 38%, P = 0.002). Hematoma occurred in 15 AS patients, in 17 SC patients, and in 14 MC patients (11 vs. 14 vs. 9%, ns)., Conclusion: There is no difference in safety between the three methods of arterial closure. SC was more often not used or successfully deployed. SC patients more often had continuing oozing. On patient comfort, closure devices performed better than MC. Early ambulation in patients with a closure device is safe. AS is the preferred method of arterial closure after cardiac catheterization., ((c) 2008 Wiley-Liss, Inc.)

Background: Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with myocardial infarction with ST-segment elevation. However, the embolization of atherothrombotic debris induces microvascular obstruction and diminishes myocardial reperfusion., Methods: We performed a randomized trial assessing whether manual aspiration was superior to conventional treatment during primary PCI. A total of 1071 patients were randomly assigned to the thrombus-aspiration group or the conventional-PCI group before undergoing coronary angiography. Aspiration was considered to be successful if there was histopathological evidence of atherothrombotic material. We assessed angiographic and electrocardiographic signs of myocardial reperfusion, as well as clinical outcome. The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively)., Results: A myocardial blush grade of 0 or 1 occurred in 17.1% of the patients in the thrombus-aspiration group and in 26.3% of those in the conventional-PCI group (P<0.001). Complete resolution of ST-segment elevation occurred in 56.6% and 44.2% of patients, respectively (P<0.001). The benefit did not show heterogeneity among the baseline levels of the prespecified covariates. At 30 days, the rate of death in patients with a myocardial blush grade of 0 or 1, 2, and 3 was 5.2%, 2.9%, and 1.0%, respectively (P=0.003), and the rate of adverse events was 14.1%, 8.8%, and 4.2%, respectively (P<0.001). Histopathological examination confirmed successful aspiration in 72.9% of patients., Conclusions: Thrombus aspiration is applicable in a large majority of patients with myocardial infarction with ST-segment elevation, and it results in better reperfusion and clinical outcomes than conventional PCI, irrespective of clinical and angiographic characteristics at baseline. (Current Controlled Trials number, ISRCTN16716833.), (Copyright 2008 Massachusetts Medical Society.)

Objective: We investigated the efficacy of oral rosuvastatin treatment to reduce in-stent neointima formation, both in the absence and presence of high levels of the proproliferative substance angiotensin II (Ang II)., Background: Drawbacks of current drug-eluting stents include inhibition of reendothelialization, induction of abnormal coronary endothelial function, and, most importantly, late in-stent thrombosis. Statin treatment might be a more subtle approach, with known beneficial vascular effects., Methods: Wistar rats were allocated to four treatment groups by two consecutive randomization steps: one to allocate rosuvastatin 0.047% (wt/wt) supplemented rat chow, and one to implant an osmotic minipump releasing Ang II (200 ng/kg). Stents were implanted in the abdominal aorta in all groups. After 4 weeks, in-stent neointima formation and vascular function in the thoracic aorta were determined., Results: In the absence of Ang II, rosuvastatin reduced neointima formation by 23% as compared with control (0.66+/-0.06 versus 0.51+/-0.02 mm2; P<0.05). The presence of Ang II enhanced neointimal area by 30%. This was inhibited to the same extent by rosuvastatin (0.88+/-0.06 versus 0.67+/-0.03 mm2; P<0.05). In parallel, rosuvastatin improved endothelial-dependent vasodilatation, both in the presence and absence of high levels of Ang II., Conclusion: Ang II infusion increases in-stent neointima formation and decreases endothelial function. We now provide evidence that rosuvastatin effectively inhibits in-stent neointima formation and in parallel improves endothelial dilator function, both in the presence and absence of high Ang II levels.

Objective: To determine the contribution of bone marrow (BM)-derived cells in in-stent restenosis (ISR) and transplant arteriosclerosis (TA)., Methods: Non-transgenic rats WT F344(TG) (n = 3) received stent implantation 6 weeks after lethal total body irradiation and suppletion with bone marrow from a R26-hPAP transgenic rat. After 4 weeks the abdominal aortas were harvested, the stent was quickly removed, the abdominal aorta was snap-frozen in liquid nitrogen and 5 mum cryosections for stainings were cut. Additionally, DA aortic allografts were transplanted into WT F344(TG) (n = 3) and R26-hPAP(WT) (n = 3) BM-chimeric recipients. Immunohistochemistry (hPAP staining) and immunofluorescence (hPAP, alpha-SMA and OX1) was performed on all sections., Results: Few hPAP-positive cells were observed in the neointima. Double stainings of hPAP-positive areas showed no alpha-SMA colocalization; OX-1 did show colocalization., Conclusions: Non-BM-derived cells are the predominant source of neointimal cells in ISR and TA. Vascular wall-derived progenitor cells may rather be the source of SMCs that contribute to ISR and TA, which may have implications for our quest for new therapeutic targets to treat these vasculopathies., (Copyright 2008 S. Karger AG, Basel.)

Objectives: To investigate the incidence and angiographic predictors of functional collateral perfusion in patients with stable coronary artery disease, scheduled for elective PCI., Background: Functional collateral perfusion is defined as a Pw/Pa ratio>or=0.24. Since this can only be measured intracoronary, it is important to investigate baseline clinical and angiographic predictors for functional collateral perfusion., Methods: Collateral perfusion was measured during balloon inflation, with the use of a pressure-monitoring guide wire. Baseline clinical and angiographic characteristics were analyzed and collateral grading was done according to Rentrop's classification for coronary angiograms., Results: Functional collateral perfusion was found in 40 of the 89 patients (45%). Angiographic signs of collaterals (Rentrop>or=1) were present in 15 of the 89 patients. Of the 40 patients with the functional collateral perfusion 11 patients (28%) had Rentrop>or=1; of the 49 patients without functional collaterals there were 4 patients with Rentrop>or=1 (8%) (P=0.02). There were no significant differences in baseline clinical characteristics or in other angiographic characteristics., Conclusions: In patients with stable coronary artery disease scheduled for elective PCI, 45% have functional collaterals. Rentrop's angiographic classification can be used to predict the presence or absence of functional collaterals, however with a rather modest positive and negative predictive value., (Copyright (c) 2007 Wiley-Liss, Inc.)

Background: Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion., Methods: Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode., Results: In group 1 the Pw/Pa ratio decreased by 10 +/- 22% from 0.20 +/- 0.09 to 0.19 +/- 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 +/- 15% from 0.22 +/- 0.09 to 0.24 +/- 0.10 (p = 0.001) when electrical neurostimulation was activated., Conclusion: Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.