Bifurcation PCI with a hybrid strategy with drug- eluting balloons versus a stepwise provisional two- stent strategy: Rationale and design of the hybrid DEB study.

The optimal treatment strategy for coronary bifurcation lesions by percutaneous coronary intervention (PCI) is complex and remains a subject of debate. Current guidelines advise a stepwise provisional approach with optional two-stent strategy. However, a two-stent strategy, both upfront and stepwise provisional, is technically demanding. Therefore, there is increasing interest in the use of drug-eluting balloons (DEB) in bifurcation lesions, mainly after a provisional approach with unsatisfactory result of the side branch. Some small pilot studies already showed that the use of DEB in bifurcation lesions is safe and feasible. However, a randomized comparison of this hybrid DEB strategy with a two-stent strategy is currently lacking. TRIAL DESIGN: The Hybrid DEB study is a prospective, multicenter, randomized controlled trial investigating noninferiority of a hybrid DEB approach, using a combination of a drug-eluting stent (DES) in the main vessel and DEB in the side branch, compared to stepwise provisional two-stent strategy in patients with true bifurcation lesions. A total of 500 patients with de novo true coronary bifurcation lesions, treated with a stepwise provisional approach and an unsatisfactory result of the side branch after main vessel stenting (≥ 70% stenosis and/or < thrombolysis in myocardial infarction III flow), will be randomized in a 1:1 ratio to receive either treatment with a DEB or with a DES in the side branch. The primary endpoint is a composite endpoint of the occurrence of all-cause death, periprocedural or spontaneous myocardial infarction and/or target vessel revascularization at the anticipated median 2-year follow-up. CONCLUSION: The Hybrid DEB study will compare in a multicenter, randomized fashion a hybrid DEB approach with a stepwise provisional two-stent strategy in patients with true bifurcation lesions. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT05731687.

Soluble interleukin 6 receptor levels are associated with reduced myocardial reperfusion after percutaneous coronary intervention for acute myocardial infarction.

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.

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.

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.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

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.

Multiple biomarkers for the prediction of short and long-term mortality after ST-segment elevation myocardial infarction: the Amsterdam Groningen collaboration.

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.

Inducible cardiac ischaemia is related to a decrease in the whole-blood Toll-like receptor 2 and 4 response.

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.

Circulating leukocyte and carotid atherosclerotic plaque telomere length: interrelation, association with plaque characteristics, and restenosis after endarterectomy.

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.

Metformin in non-diabetic patients presenting with ST elevation myocardial infarction: rationale and design of the glycometabolic intervention as adjunct to primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial.

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.

Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial.

BACKGROUND: administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. METHODS AND RESULTS: a total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P=0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P=0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group (P=0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P=0.786). CONCLUSIONS: in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size.

Thrombus aspiration during primary percutaneous coronary intervention.

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.)

Impact of chronic total occlusions on markers of reperfusion, infarct size, and long-term mortality: a substudy from the TAPAS-trial.

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.

Long-term type 1 diabetes enhances in-stent restenosis after aortic stenting in diabetes-prone BB rats.

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.

Impact of pretreatment with clopidogrel on initial patency and outcome in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review.

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.

Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study.

BACKGROUND: Percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction can be complicated by spontaneous or angioplasty-induced embolisation of atherothrombotic material. Distal blockage induces microvascular obstruction and can result in less than optimum reperfusion of viable myocardium. The Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) found that thrombus aspiration resulted in improved myocardial reperfusion compared with conventional PCI, but whether this benefit improves clinical outcome is unknown. We aimed to investigate whether the early efficacy of thrombus aspiration seen in TAPAS translated into clinical benefit after 1 year. METHODS: Patients with ST-elevation myocardial infarction enrolled at the University Medical Centre Groningen were randomly assigned in a 1:1 ratio to either thrombus aspiration or conventional treatment, before undergoing initial coronary angiography. Exclusion criteria were rescue PCI after thrombolysis and known existence of a concomitant disease with life expectancy less than 6 months. Of the 1071 patients enrolled between January, 2005, and December, 2006, vital status at or beyond 1 year after randomisation was available for 1060 (99%). The primary endpoint was cardiac death or non-fatal reinfarction after 1 year, and analysis was by intention to treat. The TAPAS trial is registered with Current Controlled Trials number ISRCTN16716833. FINDINGS: Cardiac death at 1 year was 3.6% (19 of 535 patients) in the thrombus aspiration group and 6.7% (36 of 536) in the conventional PCI group (hazard ratio [HR] 1.93; 95% CI 1.11-3.37; p=0.020). 1-year cardiac death or non-fatal reinfarction occurred in 5.6% (30 of 535) of patients in the thrombus aspiration group and 9.9% (53 of 536) of patients in the conventional PCI group (HR 1.81; 95% CI 1.16-2.84; p=0.009). INTERPRETATION: Compared with conventional PCI, thrombus aspiration before stenting of the infarcted artery seems to improve the 1-year clinical outcome after PCI for ST-elevation myocardial infarction.

Computed tomographic angiography or conventional coronary angiography in therapeutic decision-making.

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.

Non-bone marrow origin of neointimal smooth muscle cells in experimental in-stent restenosis in rats.

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.

Rosuvastatin attenuates angiotensin II-induced neointimal formation after stent implantation in the rat.

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.

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion.

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.

Pooled Analysis Comparing the Efficacy of Intracoronary Versus Intravenous Abciximab in Smokers Versus Nonsmokers Undergoing Primary Percutaneous Coronary Revascularization for Acute ST-Elevation Myocardial Infarction.

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.