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Objectives We present the 5-year clinical outcomes according to treatment strategy with additional risk stratification of the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial. Background Long-term outcomes may be relevant to decide treatment strategy for patients presenting with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) and elevated troponin T. Methods We randomly assigned 1,200 patients to an early invasive or selective invasive strategy. The outcomes were the composite of death or myocardial infarction (MI) and its individual components. Risk stratification was performed with the FRISC (Fast Revascularization in InStability in Coronary artery disease) risk score. Results At 5-year follow-up, revascularization rates were 81% in the early invasive and 60% in the selective invasive group. Cumulative death or MI rates were 22.3% and 18.1%, respectively (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.00 to 1.66, p = 0.053). No difference was observed in mortality (HR: 1.13, 95% CI: 0.80 to 1.60, p = 0.49) or MI (HR: 1.24, 95% CI: 0.90 to 1.70, p = 0.20). After risk stratification, no benefit of an early invasive strategy was observed in reducing death or spontaneous MI in any of the risk groups. Conclusions In patients presenting with NSTE-ACS and elevated troponin T, we could not demonstrate a long-term benefit of an early invasive strategy in reducing death or MI. (Invasive versus Conservative Treatment in Unstable coronary Syndromes [ICTUS]; ISRCTN82153174 )

Aims Despite improvement in prognosis for ST-elevation myocardial infarction (STEMI) patients, mortality remains high in STEMI patients presenting with cardiogenic shock (CS). Right ventricular (RV) dysfunction is an established independent predictor for adverse prognosis in STEMI patients without CS. The purpose of our study was to determine the prognostic value of RV dysfunction on admission in STEMI patients presenting in CS. Methods and results Two hundred and ninety-two consecutive STEMI patients with CS on admission were treated by primary percutaneous coronary intervention (PCI) from January 1997 through March 2005. RV function was assessed by measurement of tricuspid annular plane systolic excursion (TAPSE) on early echocardiography in 184 of 292 patients. Right ventricular dysfunction was defined as a TAPSE of ≤14 mm. Right ventricular dysfunction was present on early echocardiography in 70 of 184 patients (38%). The Kaplan–Meier estimate for overall 4-year survival was 57%. Kaplan–Meier estimates for 4-year survival in patients with and without RV dysfunction were 33 and 73%, respectively (P< 0.001). Cox-regression analysis revealed a hazard ratio of 2.1 (95% CI 1.3–3.4, P = 0.002) for RV dysfunction when adjusted for age, glucose on admission, and LVEF < 40%. In patients with and without RV dysfunction, the right coronary artery was the infarct-related artery in 41 and 28% of patients, respectively (P = 0.06). Conclusion In STEMI patients presenting with CS on admission and treated with primary PCI, RV dysfunction as assessed by echocardiography is an independent predictor for long-term mortality.

Aims Despite the advances in treatment for acute ST-elevation myocardial infarction (STEMI) during the past decades for both men and women, most previous studies reported on significantly higher unadjusted in-hospital and long-term mortality rates among women compared with men. Most of these studies have been performed in the (pre-)thrombolytic and early post-thrombolytic era. Many studies reported on myocardial infarction or acute coronary syndromes and did not specifically address STEMI. Moreover, the association of gender, quality of care and mortality has not been systematically assessed. Methods and results Early as well as long-term clinical outcome and delivered quality care was evaluated in an unselected cohort of 3,277 (2,367 men and 910 women) consecutive STEMI patients treated by primary PCI in a tertiary referral institution between January 1995 and 2006. Mean follow-up was 3.2+/-2.2 years. The unadjusted early and late hazards of mortality were not significantly different between men and women (30-days HR 0.87; 95%CI 0.67-1.12; 3-year HR 0.87; 95%CI 0.71-1.10), despite more adverse clinical characteristics in women. Gender was not an independent predictor for mortality and adjustment for covariates did not alter these results. Quality of care was similar between both sexes. Conclusions Despite higher age and more disadvantageous clinical characteristics, unadjusted early as well as long-term mortality in women with STEMI treated by primary PCI was equal compared with men. Women have longer ischaemic times compared with men but not due to a difference in delivered care. Quality of care before, during and after reperfusion was equal for men and women.

Objective The general population is gradually ageing in the western world. Therefore, the number of octogenarians undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is increasing. We aim to provide insight into temporal trends in the annual proportions of octogenarians among STEMI patients undergoing primary PCI and their clinical characteristics and outcomes over an 11-year observational period. Design Single-centre observational study. Patients Between 1997 and 2007, 4506 STEMI patients were treated with primary PCI at the authors’ institution. Patients aged over 80 years were identified. Main outcome measures Temporal trends in the annual proportion of octogenarian STEMI patients and their baseline characteristics, 30-day and 1-year mortality were analysed. Results A total of 379 octogenarians (8.4% of the total population) was treated with primary PCI between 1997 and 2007. Over time, the annual proportion of octogenarians gradually increased from four of 113 (3.5%) in 1997 to 51 of 579 (8.8%) in 2007 (p for trend

Background Recently, a chronic total occlusion (CTO) in a non-infarct-related artery (non-IRA) and not multivessel disease (MVD) alone was identified as an independent predictor of mortality after ST elevation myocardial infarction (STEMI). Patients with diabetes mellitus (DM) constitute a patient group with a high prevalence of MVD and high mortality after STEMI. The prevalence of CTO in a non-IRA was studied and its impact on long-term mortality in STEMI patients with DM was investigated. Methods Between 1997 and 2007 4506 patients with STEMI were admitted and treated with primary percutaneous coronary intervention (PCI). Patients with DM were identified. The patients were categorised as having single vessel disease (SVD), MVD without CTO and CTO based on the angiogram before PCI. Results A total of 539 patients (12%) had DM. MVD with or without a CTO was present in 33% of non-diabetic patients and in 51% of diabetic patients. The prevalence of a CTO in a non-IRA was 21% in STEMI patients with DM and 12% in STEMI patients without DM (p

Objectives: To evaluate the long-term outcomes of the selected patients by the local Heart Team to undergo percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) stenosis and to compare patients considered at low surgical risk versus at high surgical risk for coronary artery bypass grafting (CABG). Background: CABG is recommended in patients with ULMCA stenosis according to the AHA/ACC and ESC guidelines, and there are limited data on the long-term outcomes in patients selected by the local Heart Team to undergo PCI. Methods: Between 1996 and 2007, 227 patients underwent PCI for ULMCA stenosis based on decision of the local Heart Team and patient's and/or physician's preference. All patients were contacted at 1 year and in November 2008. Results: Long-term follow-up was up to 8 years with a mean of 3.9 +/- 2.6 years. Overall, the Kaplan-Meier estimate of the composite of cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR) was 14.8% at 1 year, 18.3% at 3 years, and 20.9% at 5 years with no events occurring thereafter. Patients considered at low surgical risk for CABG had a significantly lower incidence of cardiac death or MI compared to patients considered at high surgical risk at 8 years (1.4 vs. 16.8%; 1.4 vs. 14.8%, respectively); however, no significant difference was observed for cardiac death, MI, or TLR (18.6 vs. 24.4%). Conclusions: PCI of ULMCA stenosis in patients selected by the Heart Team resulted in good long-term clinical outcomes with most events occurring within the 1st year. Patients considered at low surgical risk for CABG have a significantly better long-term survival than patients at high risk for surgery. (C) 2010 Wiley-Liss, Inc

We aimed to describe the logistics of a prehospital triage system for patients with acute chest pain in the region of Amsterdam, The Netherlands. Ambulance electrocardiograms (ECGs) were evaluated immediately in 1 of the percutaneous coronary intervention (PCI)-capable centers. Patients accepted for primary PCI (PPCI) were directly transferred to the catheterization laboratory. Two thousand three hundred fifty ECGs of 2,192 patients were transmitted to the region's intervention centers. Median duration of chest complaints before ambulance dispatch was 67 minutes; ambulance crews recorded the first ECG within 7 minutes after arrival. Actual transmission of the ECG took an additional (median) 10 minutes. Seven hundred eleven patients (32.4%) were transported to the catheter laboratory and were treated with PPCI. Time between first prehospital ECG and start of PPCI procedure was 66 minutes. The PPCI procedure started 36 minutes after ambulance arrival at the hospital. In conclusion, the results of this study compare favorably to other reported performances of prehospital triage systems of PPCI for ST-segment elevated myocardial infarction and demonstrate that the European Society of Cardiology and American Heart Association guidelines for treatment of patients with ST-segment elevated myocardial infarction can be met. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106: 931-935)

AIMS To study online left ventricular (LV) dynamic effects of transmural ischaemia and reperfusion during consecutive balloon coronary occlusions in the setting of percutaneous coronary intervention (PCI). METHODS AND RESULTS In 10 consecutive unselected patients with stable angina (seven males, mean age 62 ± 3 years) who underwent elective PCI, LV dynamics were continuously recorded using a pressure-conductance catheter to simultaneously measure pressure and volume (PV-loop). The effects of a prolonged balloon coronary occlusion (148 ± 19 s) and a second occlusion on various LV function parameters were studied, as well as recovery of these parameters after reperfusion. Ischaemia caused an immediate (

Objectives: We studied online left ventricular (LV) dynamic effects of mechanical LV unloading directly after percutaneous coronary intervention (PCI). Background: Limited clinical information is available on the direct LV dynamic consequences of LV unloading in patients undergoing high-risk PCI and primary PCI for acute ST-elevation myocardial infarction. Methods: The effects of the Impella LP2.5 device on LV dynamics were studied in 11 patients (elective high-risk PCI, n = 6; primary PCI, n = 5). LV pressure and volume were continuously assessed by a pressure-conductance catheter at 4 different support levels of the Impella, from 0 L/min at baseline to 2.5 L/min at maximal support. Results: The response to increased LV unloading was not different between both groups of patients. The pooled data showed no change on global and systolic LV function during increased LV unloading, while diastolic function showed improvement as indicated by an increased LV compliance in all patients. There was a decrease in end-diastolic pressure from 22 ± 12 to 13 ± 9 mm Hg (P = 0.0001), in end-diastolic elastance from 0.134 ± 0.060 to 0.091 ± 0.064 mm Hg/mL (P = 0.009), and in end-diastolic wall stress from 84 ± 50 to 47 ± 39 mm Hg (P = 0.004). Conclusions: LV unloading decreases end-diastolic wall stress and improves diastolic compliance dose-dependently. Our results indicate beneficial LV unloading effects of Impella during high-risk and primary PCI. © 2009 Wiley-Liss, Inc.

Data on the ability of serum biomarkers to predict microvascular obstruction by ST-segment recovery after primary percutaneous coronary intervention (PCI) is largely absent. Therefore, we determined the association between 5 serum biomarkers, obtained before emergency coronary angiography, and immediate ST-segment recovery in patients who had undergone primary PCI for ST-segment elevation myocardial infarction. We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and serum creatinine from blood samples obtained through the arterial sheath at the start of primary PCI. Serial 12-lead electrocardiograms were recorded in the catheterization laboratory before arterial puncture and at the end of the PCI. ST-segment recovery was defined as incomplete if = 608 ng/L) was the strongest predictor of incomplete ST-segment recovery (adjusted odds ratio 2.6, 95% confidence interval 1.6 to 4.1; p

Objectives The aim of this study was to evaluate the effect of a concurrent chronic total occlusion (CTO) in patients with ST-segment elevation myocardial infarction (STEMI) on long-term mortality and left ventricular ejection fraction (LVEF). Background The impact of a CTO in a non-infarct-related artery (IRA) on prognosis after STEMI is unknown. Methods Between 1997 and 2005, we admitted 3,277 STEMI patients treated with primary percutaneous coronary intervention. Patients were categorized as single-vessel disease (SVD), multivessel disease (MVD) without CTO, and MVD with a CTO in a non-IRA. We performed a "landmark survival analysis" to 5 years follow-up with a landmark set at 30 days. Additionally, we analyzed the evolution of LVEF within 1 year. Results Of the patients, 2,115 (65%) had SVD, 742 patients (23%) had MVD without CTO, and 420 patients (13%) had a concurrent CTO. Presence of a CTO was a strong and independent predictor for 30-day mortality (hazard ratio [HR]: 3.6, 95% confidence interval [CI]: 2.6 to 4.7, p

Aims The purpose of this study was to evaluate the Genous(TM) endothelial progenitor cell capturing stent vs. the Taxus Liberté paclitaxel-eluting stent in patients with de novo coronary lesions with a high-risk of coronary restenosis. Methods and results We randomly assigned 193 patients with lesions carrying a high risk of restenosis to have the Genous stent or the Taxus stent implanted. Lesions were considered high risk of restenosis if one of the following applied: chronic total occlusion, lesion length >23 mm, vessel diameter

Objectives The purpose of this study was to evaluate the effectiveness of combined proximal embolic protection with thrombus aspiration (Proxis Embolic Protection System [St. Jude Medical, St. Paul, Minnesota]) in ST-segment elevation myocardial infarction patients. Background Embolization during primary percutaneous coronary intervention (PCI) may result in microvascular obstruction, reduced myocardial perfusion, and impaired prognosis. Methods Two hundred eight-four patients were randomized to primary PCI with the Proxis system versus primary PCI alone after angiography. The primary end point was the occurrence of complete (>= 70%) ST-segment resolution (STR) at 60 min measured by continuous ST-segment Holter. Results There was no significant difference in the occurrence of the primary end point (80% vs. 72%, p = 0.14). However, immediate complete STR (at time of last contrast) occurred in 66% of Proxis-treated patients and 50% in control patients (absolute difference, 16.3%; 95% confidence interval: 4.3% to 28.2%; p = 0.009). A significant lower ST-segment curve area (0 to 3 h after primary PCI) was observed in the Proxis arm (5,192 mu V/min vs. 6,250 mu V/min, p = 0.037). Major adverse cardiac and cerebral events at 30 days occurred with similar frequency in both groups (6 vs. 10). Conclusions There was no significant difference in complete STR at 60 min in this proof-of-concept study. However, we observed a significant difference in immediate complete SIR in Proxis-treated patients, better SIR at later time points, and a reduction of electrocardiogram injury current over time, compared with control patients. The results suggest that primary PCI with the Proxis system may lead to better immediate microvascular flow in ST-segment elevation myocardial infarction patients. (The PREPARE Study; ISRCTN71104460) (J Am Coll Cardiol Intv 2009;2:934-43) (c) 2009 by the American College of Cardiology Foundation

Objectives We studied the left ventricular (LV) dynamic effects of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) by directly obtaining pressure–volume (PV) loops during the procedure. Background An acute myocardial infarction causes a decrease in LV compliance. The instantaneous effects of primary PCI on LV compliance are unknown. Methods We studied 15 consecutive patients (10 males, ages 59 ± 12 years), who presented with their first acute anterior STEMI within 6 h after onset of symptoms, and in whom coronary angiography revealed an occluded left anterior descending coronary artery. Before performing primary PCI, we inserted a pressure-conductance catheter in the LV to continuously obtain PV loops. Results Immediately after successful reperfusion, significant improvements were observed in LV diastolic function, as indicated by an increased end-diastolic compliance with a 6.0 ± 2.8 mm Hg (p Conclusions Primary PCI in anterior STEMI patients causes an immediate improvement in diastolic function, assessed by online PV loop measurements.

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:604-610)

Aims Aim of this study was to investigate the diagnostic accuracy of the conventional electrocardiogram (ECG) algorithm [ST-segment elevation (STE) in lead III exceeding that in lead II combined with ST-segment depression in lead I or aVL] for identification of the infarct-related artery (IRA) in a large cohort of patients undergoing primary percutaneous coronary intervention (PCI) for inferior wall STE myocardial infarction (STEMI). Methods and results We included 1131 patients with inferior STEMI, who underwent primary PCI between 2000 and 2007 and of whom a pre-procedural 12-lead ECG was available, recorded immediately prior to PCI. The IRA was determined during emergency angiography. Coronary angiography confirmed the right coronary artery (RCA) as the IRA in 895 patients (79%) with inferior wall STEMI. Application of the ECG algorithm resulted in 624 true positive cases of acute RCA obstruction (sensitivity: 70%, 95% CI: 67 –73%) and 170 cases with true negative result (specificity: 72%, 95% CI: 66–77%). Sensitivity of >90% was established in patients with cumulative ST-segment deviation above median (>18.5 mm). Conclusion The conventional ECG algorithm showed a low sensitivity for the non-invasive diagnosis of RCA occlusion in an all-comer, inferior STEMI cohort undergoing primary PCI. Sensitivity was only sufficient in patients with extensive ST-segment deviation.

Aims In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial. Methods and results The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37–0.96] and 0.46 (95% CI 0.31–0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70–1.74) for death and 1.27 (95% CI 0.88–1.85) for death or spontaneous MI. Conclusion The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies.

Variation in theNOS3gene has been related to the development of restenosis. The Glu298Asp polymorphism has previously been investigated for its effect on NO levels and the development of restenosis. However, the variability of findings gave rise to the hypothesis that the functional significance of this polymorphism may only become manifest under conditions of endothelial dysfunction. Since patients with the metabolic syndrome are known to have endothelial dysfunction, we aimed to investigate if the significance ofNOS3polymorphisms may depend on the presence of the metabolic syndrome.We examined the impact of the -949 A/G, the -716 C/T and the Glu298Asp polymorphisms in theNOS3gene on the risk of clinical restenosis in a previously described subpopulation of the GENDER-study, a multicenter prospective study design that enrolled consecutive patients after successful PCI. This subpopulation consisted of 901 patients of whom sufficient data were available to establish absence or presence of the metabolic syndrome. Of these patients, 448 had the metabolic syndrome. Clinical restenosis, defined as target vessel revascularization (TVR), was the primary endpoint.We demonstrated that the minor -949G, -716T and 298Asp alleles were associated with a significantly increased risk of TVR in patients with the metabolic syndrome (HR: 1.58 [95%CI: 1.04–2.40], HR: 1.95 [95%CI: 1.02–3.70] and HR: 1.67 [95%CI: 1.09–2.54], respectively). In the group without the metabolic syndrome we observed no association between the three polymorphisms and TVR.

Background— The cyclin-dependent kinase inhibitor p27 kip1 is a key regulator of smooth muscle cell and leukocyte proliferation in vascular disease, including in-stent restenosis. We therefore hypothesized that common genetic variations or single nucleotide polymorphisms in p27 kip1 may serve as a useful tool in risk stratification for in-stent restenosis. Methods and Results— Three single nucleotide polymorphisms concerning the p27 kip1 gene (−838C>A, rs36228499; −79C>T, rs34330; +326G>T, rs2066827) were determined in a cohort of 715 patients undergoing coronary angioplasty and stent placement. We discovered that the p27 kip1 -838C>A single nucleotide polymorphism is associated with clinical in-stent restenosis; the −838AA genotype decreases the risk of target vessel revascularization (hazard ratio, 0.28; 95% confidence interval, 0.10 to 0.77). This finding was replicated in another cohort study of 2309 patients (hazard ratio, 0.61; 95% confidence interval, 0.40 to 0.93). No association was detected between this end point and the p27 kip1 -79C>T and +326G>T single nucleotide polymorphisms. We subsequently studied the functional importance of the −838C>A single nucleotide polymorphism and detected a 20-fold increased basal p27 kip1 transcriptional activity of the −838A allele containing promoter. Conclusions— Patients with the p27 kip1 -838AA genotype have a decreased risk of in-stent restenosis corresponding with enhanced promoter activity of the −838A allele of this cell-cycle inhibitor, which may explain decreased smooth muscle cell proliferation.

Aims Intra-aortic balloon counterpulsation (IABP) in ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock is strongly recommended (class IB) in the current guidelines. We performed meta-analyses to evaluate the evidence for IABP in STEMI with and without cardiogenic shock. Methods and results Medical literature databases were scrutinized to identify randomized trials comparing IABP with no IABP in STEMI. In absence of randomized trials, cohort studies of IABP in STEMI with cardiogenic shock were identified. Two separate meta-analyses were performed respectively. The first meta-analysis included seven randomized trials (n = 1009) of STEMI. IABP showed neither a 30-day survival benefit nor improved left ventricular ejection fraction, while being associated with significantly higher stroke and bleeding rates. The second meta-analysis included nine cohorts of STEMI patients with cardiogenic shock (n = 10529). In patients treated with thrombolysis, IABP was associated with an 18% [95% confidence interval (CI), 16-20%; P < 0.0001] decrease in 30 day mortality, albeit with significantly higher revascularization rates compared to patients without support. Contrariwise, in patients treated with primary percutaneous coronary intervention, IABP was associated with a 6% (95% CI, 3-10%; P < 0.0008) increase in 30 day mortality. Conclusion The pooled randomized data do not support IABP in patients with high-risk STEMI. The meta-analysis of cohort studies in the setting of STEMI complicated by cardiogenic shock supported IABP therapy adjunctive to thrombolysis. In contrast, the observational data did not support IABP therapy adjunctive to primary PCI. All available observational data concerning IABP therapy in the setting of cardiogenic shock is importantly hampered by bias and confounding. There is insufficient evidence endorsing the current guideline recommendation for the use of IABP therapy in the setting of STEMI complicated by cardiogenic shock. Our meta-analyses challenge the current guideline recommendations.

Aims: Haemoglobin based oxygen carriers (HBOCs) are considered in the treatment of patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). In light of their potential vasopressor and colloidal properties, their effect on coronary physiology, safety and tolerability needs to be established. Methods and results: In this phase II pilot trial, 45 patients were randomly assigned, (1:1:1) to double blind treatment with a 30 minute intravenous (IV) infusion of either 15 or 30 g of HBOC-201, compared to an equivalent volume of non-oxygen carrier colloid control. Systemic, pulmonary, and coronary haemodynamics were studied during this infusion period. IV HBOC-201 administration produced an increase in systolic blood pressure (SBP), pulmonary capillary wedge pressure and calculated systemic vascular resistance (SVR) and a concomitant decrease in cardiac output (CO); there was a decrease in mixed venous saturation (SV02) following IV HBOC-201. The left ventricular stroke work index (LVSWI) was not altered by HBOC-201 treatment. Of note, no coronary vasoconstriction was observed, nor were there significant changes in resting average peak velocity (APV), coronary-artery diameter, volumetric coronary blood flow, or coronary vascular resistance. The percentage of patients with adverse events did not differ between the HBOC-201 treated and control groups (76% vs. 63%, respectively, P=0.49). Seven se'ious adverse events (SAE) occurred in six patients in the treatment group and two in two patients in the control group. Only one SAE (hypertension) was judged HBOC-201 related. Patients in both the HBOC-201 and control group had a similar incidence of increased liver alanine transaminase (31% vs 31%, respectively, NS); 10% of the patients in the HBOC-201 group had increases greater than three times the upper limit of normal. Differential increases were noticed in some inflammatory markers (IL-6. CRP) 18-24 hours after infusion between the HBOC-201 arms and the control group. Conclusion: No compromise in the coronary blood flow or LVSWI was observed despite HBOC-201's known vasoactive effects. One SAE was adjudicated as "drug related" and fully resolved. The clinical relevance of the differential rise in certain biochemical markers and the adverse effects of plasma haemoglobin in the context of ACS needs further investigation.

The aim of the present study was to determine whether there is a linear relation between the doses measured above and those measured under the lead apron of the radiologists performing interventional procedures. To monitor radiation exposure the International Commission of Radiological Protection (ICRP) recommends the use of a single dosimeter under the protective apron. To determine the exposure more accurately an additional dosimeter is recommended above the protective apron. The exposure of eight radiologists was monitored with two personal dosimeters during 3 consecutive years. To measure the doses uniformly the two dosimeters were worn in a special holder attached to the lead apron. The two personal dosimeters were replaced every 4 weeks on the same day. The doses above and under the protective aprons of seven radiologists did not differ significantly. A significant lower dose above and under the protective apron was measured for one of the radiologists. During a 4-week period the average dose measured above the lead apron was 3.44 mSv (median, 3.05 mSv), while that under the 0.25-mm lead apron was 0.12 mSv (median, 0.1 mSv). The coefficients of the regression line result in the equation Y = 0.036X − 0.004, with Y as the dose under the lead apron and X as the dose above the lead apron. The statistical analysis of the data established a linear relation between the doses above and those under the lead apron (R2 = 0.59). Before the special holder was introduced it was not possible to derive a relation between the doses above and those under the lead apron, as the doses were measured at varying places above and under the lead apron. There is no evidence that the effective dose can be estimated more accurately when an additional dosimeter is used. The present study revealed a threshold before doses under the lead apron were measured. Due to the threshold it can be concluded that the doses under the lead apron will not be underestimated easily when doses above the lead apron are used to calculate them. This is not the case when the doses above the lead apron are calculated for the doses under the lead apron.

Background— Routine thrombus aspiration is frequently used during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction to prevent distal embolization. Recently, evidence of clinical benefit was published. In 50% of the ST-elevation myocardial infarction patients with an onset of symptoms 1 day old. This observation illustrates that plaque rupture and coronary occlusion are significantly separated in time. In the present study, we correlate the presence of fresh versus older thrombus with long-term mortality. Methods and Results— Thrombus aspiration was performed in 1315 patients treated with primary percutaneous coronary intervention with 3 devices (Rescue, Export, and Proxis). Aspirated material was fixed in formalin and processed for histopathology. If possible, thrombus age was classified as either fresh only (1 day). We identified fresh thrombus in 552 patients and older thrombus in 372 patients. The cumulative Kaplan-Meier estimate of all-cause mortality at 4 years was significantly higher in patients with older thrombus (16.0%) compared with patients with fresh thrombus (7.4%), with a hazard ratio of 1.82 (95% confidence interval, 1.17 to 2.85; P =0.008). Multivariate analysis identified the presence of older thrombus, in addition to other established predictors, as an independent predictor (hazard ratio, 1.83; 95% confidence interval, 1.14 to 2.93; P =0.01) of long-term mortality. Conclusion— Our study demonstrates that the presence of older thrombus, in addition to other established predictors, is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention.

The platelet receptor P2Y12 (gene symbol P2RY12) is involved in several processes that contribute to restenosis after percutaneous coronary interventions (PCI). Therefore, common variation in the P2Y12 gene may serve as a useful marker for risk stratification. We studied whether common variation in the platelet receptor P2Y12 gene affects the risk of restenosis after PCI. Comprehensive coverage of common variation in the P2Y12 gene was obtained by genotyping five haplotype-tagging SNPs (ht-SNPs) in 2,062 PCI-treated patients who received a stent and participated in the GENetic DEterminants of Restenosis (GENDER) Study. Haplotypes were inferred and their association with target vessel revascularization (TVR) was studied. Seven P2Y12 haplotypes were identified with an allelic frequency above 5% (designated here H1 to H7) of which two (H5 and H7) were associated with a higher risk of TVR (hazard ratios [HR]=1.4, 95% confidence interval [CI]=1.0–2.0; and HR=1.6, 95% CI=1.2–2.0, respectively) than the reference P2Y12 haplotype (H1), which contains the common alleles of all five P2Y12 ht-SNPs. Our study shows that common variation in the P2Y12 gene predicts restenosis in PCI-treated patients. Hum Mutat 29(3), 375-380, 2008. © 2008 Wiley-Liss, Inc.

Background We assessed the prognostic significance of the presence of cumulative ( ∑ ) ST-segment deviation on the admission electrocardiogram (ECG) in patients with non–ST-elevation acute coronary syndrome and an elevated troponin T randomized to a selective invasive (SI) or an early invasive treatment strategy. Methods A 12-lead ECG obtained at admission was available for analysis from 1163 patients. The presence and magnitude of ST-segment deviation was measured in each lead, and absolute ST-segment deviation was summed. The effect of treatment strategy was assessed for patients with or without ∑ ST-segment deviation of at least 1 mm. Results The incidence of death or myocardial infarction (MI) by 1 year in patients with ∑ ST-segment deviation of at least 1 mm was 18.0% compared with 11.1% in patients with ∑ ST-segment deviation of less than 1 mm ( P = .001). Among patients with ∑ ST-segment deviation of at least 1 mm, the incidence of death or MI was 21.9% in the early invasive group compared with 14.2% in SI group ( P ∑ ST-segment deviation of at least 1 mm randomized to SI who did not undergo angiography compared with patients who underwent angiography before discharge (10.9% vs 2.4%, P = .003). In a forward logistic regression analysis, the presence of ST-segment deviation was an independent predictor for failure of medical therapy (coronary angiography within 30 days after randomization in the SI group) (odds ratio, 1.56; 95% confidence interval, 1.12-2.18; P = .009). Conclusion Patients with non–ST-elevation acute coronary syndrome and an elevated troponin T and ∑ ST-segment deviation of at least 1 mm are at increased risk of death or MI, more often fail on medical therapy, and more often experience a spontaneous MI after discharge when angiography was not performed during initial hospitalization.

Contains fulltext : 53418.pdf (Publisher’s version ) (Closed access) BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this study was to assess the association between baseline NT-proBNP levels and outcome in patients who have nSTE-ACS with an elevated cTnT and to determine whether patients with elevated NT-proBNP levels benefit from an early invasive treatment strategy. METHODS: Baseline samples for NT-proBNP measurements were available in 1141 patients who have nSTE-ACS with an elevated cTnT randomized to an early or a selective invasive strategy. Patients were followed-up for the occurrence of death, myocardial infarction (MI), and rehospitalization for angina. RESULTS: We showed that increased levels of NT-proBNP were associated with several indicators of risk and severe coronary artery disease. Mortality by 1 year was 7.3% in the highest quartile (> or = 1170 ng/L for men, > or = 2150 ng/L for women) compared with 1.1% of patients in the lower 3 quartiles (P < .0001). N-terminal pro-brain natriuretic peptide (highest quartile vs lower 3 quartiles) was a strong independent predictor of mortality (hazard ratio 5.0, 95% CI 2.1-11.6, P = .0002). However, NT-proBNP levels were not associated with the incidence of recurrent MI by 1 year. Furthermore, we could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy in patients with an elevated NT-proBNP level. CONCLUSIONS: We confirmed that NT-proBNP is a strong independent predictor of mortality by 1 year but not of recurrent MI in patients who have nSTE-ACS with an elevated cTnT. We could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy.

Background Primary percutaneous coronary intervention (PCI) reduces mortality in patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). Despite PCI, mortality in CS is still approximately 50%. Admission glucose concentration is an independent predictor of mortality in patients with STEMI and is associated with the occurrence of CS. Whether admission glucose is also a predictor of mortality in CS patients treated with primary PCI is unexplored. We therefore assessed the relation between admission glucose concentration and 1-year mortality in patients with STEMI with CS without a prior diagnosis of diabetes on admission and treated with PCI. Methods We investigated a cohort of 208 consecutive patients with STEMI without a prior diagnosis of diabetes with CS on admission. Patients were classified according to glucose levels at admission: 11.0 mmol/L (group 3, n = 80). Results The overall 1-year mortality was 38%. One-year mortality was 21%, 27%, and 60% in groups 1, 11, and 111, respectively (P

The study compared, by intravascular ultrasound (IVUS), acute gain (AG) at the site of the pre-procedural minimal lumen area (MLA) achieved by either the Absorb (Abbott Vascular, Santa Clara, California) scaffold or the Xience stent and identified the factors contributing to the acute performance of these devices.It is warranted that the acute performance of Absorb matches that of metallic stents; however, concern exists about acute expansion and lumen gain with the use of Absorb.Of a total of 501 patients (546 lesions) in the ABSORB II (ABSORB II Randomized Controlled Trial) randomized trial, 445 patients with 480 lesions were investigated by IVUS pre- and post-procedure. Comparison of MLA pre- and post-procedure was performed at the MLA site by matching pre- and post-procedural IVUS pullbacks.Lower AG on IVUS (lowest tertile) occurred more frequently in the Absorb arm than in the Xience arm (3.46 mm(2) vs. 4.27 mm(2), respectively; p 0.001; risk ratio: 3.04; 95% confidence interval: 1.94 to 4.76). The plaque morphology at the MLA cross-section was not independently associated with IVUS acute gain. The main difference in AG in MLD by angiography was observed at the time of device implantation (Xience vs. Absorb, Δ+1.50 mm vs. Δ+1.23 mm, respectively), whereas the gain from post-dilation was similar between the 2 arms (Δ+0.16 mm vs. Δ+0.16 mm) when patients underwent post-dilation, although expected balloon diameter was smaller in the Absorb arm than in the Xience arm (p = 0.003) during post-dilation.At the site of the pre-procedural MLA, the increase of the lumen post-procedure was smaller in the Absorb-arm than in the Xience arm. To achieve equivalent AG to Xience, the implantation of Absorb may require more aggressive strategies at implantation, pre- and post-dilation than the technique used in the ABSORB II trial. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281).

Drug-eluting stents (DES) reduce angiographic restenosis and enhance event-free survival compared with bare-metal stents after implantation in coronary arteries. Limitations of current DES remain stent thrombosis and neo-atherosclerosis related to impaired healing, and repeat revascularization due

Background The introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface. Methods Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions. Results Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation. Conclusion We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.

Timely reperfusion therapy by means of primary percutaneous coronary intervention (PCI) is the preferred treatment for patients with ST-segment elevation myocardial infarction. A significant number of patients with large acute myocardial infarction, caused by occlusion of an epicardial coronary artery, do not show ST-elevation on the electrocardiogram. Other ECG abnormalities may be present, the so called STEMI-equivalents. One such STEMI equivalent, junctional ST-segment depression followed by tall symmetrical T-waves in the precordial leads, often in combination with slight ST-elevation in lead AVR, has been associated with proximal occlusion of the left anterior descending coronary artery. Recognition of this ECG pattern by ambulance staff, emergency physicians and interventional cardiologists envolved in STEMI networks, is important to ensure timely reperfusion therapy in these patients. In this paper we present three patients with typical symptoms of acute myocardial infarction and the ECG pattern with slight J-point depression combined with tall, symmetrical T-waves.

Background: Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) poses a high-risk for distal coronary thromboembolic events. Glycoprotein IIb/IIIa inhibitors are frequently used in hope of reducing the impact of this, although the safety and efficacy of these drugs to improve outcomes in this setting are understudied. Methods: Patients were included if they had prior coronary artery bypass surgery and subsequently underwent PCI of >= 1 SVG graft at a Dutch academic center between 1997 and 2008. These patients were matched 1: 1 based on peri-procedural use of abciximab using a propensity-score matching algorithm based on 17 variables. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between abciximab use and MACCE (the composite measure of mortality, myocardial infarction, stroke and repeat revascularization) at 30 days and up to 1 year. Results: The composite of 30-day MACCE occurred in 18 patients (15.3%) in the abciximab group and 16 patients (13.6%) in the propensity matched control group (OR: 1.13, 95% CI: 0.57-2.21, p = 0.73). At 1-year follow-up, MACCE rates were also similar (32.5% vs. 33.9%, HR: 0.97, 95% CI: 0.59-1.59). Major bleeding (BARC types 3a-c) was higher in the abciximab group (11.9% vs. 4.2%, OR: 2.80, 95% CI: 1.01-7.77). Ischemic outcomes did not differ among patients with acute coronary syndromes. Conclusion: The use of intravenous abciximab was not associated with improved clinical outcomes up to 1-year among patients undergoing SVG PCI, but was related to more bleeding. (C) 2015 Elsevier Inc. All rights reserved.

Objectives Valuable treatment modalities for branch pulmonary artery (BPA) stenoses are surgical patch angioplasty, percutaneous BPA stenting and hybrid stent placement. The purpose of this study was to report our institutional experience with hybrid stent placement to relieve BPA stenoses. Methods Between August 2007 and May 2014, 7 adults (5 females) with congenital heart disease (CHD) had elective intraoperative BPA stent placement. All 7 patients had undergone previous surgery [6 tetralogy of Fallot repairs and 1 arterial switch operation for transposition of the great arteries (TGAs)]. A total of 7 stents (4 right pulmonary artery, 3 left pulmonary artery) were implanted under direct vision, concomitant with a pulmonary homograft implantation (tetralogy of Fallot patients), or because percutaneous stenting was not feasible (TGA patient). Retrospective analysis of clinical data, procedural details and outcomes was performed. Results Overall, the mean age was 35 ± 7.2 years. Stent implantation was successful in all procedures. The mean postinflation stent diameter was 13.3 ± 2.0 mm. No stent migration, fracture, stent thrombosis, reintervention or deaths occurred. In 1 case the procedure was complicated by a right pulmonary artery tear just distal to the stent which was repaired by surgical patch angioplasty. At a mean follow-up of 55.6 ± 26 months no patient required catheter reintervention or surgery. Echocardiography (mean follow-up 47.1 ± 22 months), MRI (mean follow-up 43.8 ± 37 months) and CT data (mean follow-up 14.8 ± 10 months) demonstrate a BPA diameter increment from a mean 5.57 ± 2.29 to 10.71 ± 2.56 mm. Conclusions Hybrid intraoperative BPA stent placement is safe and effective and can be used as an alternative for surgical patch angioplasty or if percutaneous BPA stenting is not feasible. Short- to mid-term results are good.

Background and Aims Since high-density lipoprotein (HDL) has pro-endothelial and anti-thrombotic effects, a HDL recruiting stent may prevent restenosis. In the present study we address the functional characteristics of an apolipoprotein A-I (ApoA-I) antibody coating in vitro. Subsequently, we tested its biological performance applied on stents in vivo in rabbits. Materials and Methods The impact of anti ApoA-I- versus apoB-antibody coated stainless steel discs were evaluated in vitro for endothelial cell adhesion, thrombin generation and platelet adhesion. In vivo, response to injury in the iliac artery of New Zealand white rabbits was used as read out comparing apoA-I-coated versus bare metal stents. Results ApoA-I antibody coated metal discs showed increased endothelial cell adhesion and proliferation and decreased thrombin generation and platelet adhesion, compared to control discs. In vivo, no difference was observed between ApoA-I and BMS stents in lumen stenosis (23.3±13.8% versus 23.3±11.3%, p=0.77) or intima surface area (0.81±0.62 mm2 vs 0.84±0.55 mm2, p=0.85). Immunohistochemistry also revealed no differences in cell proliferation, fibrin deposition, inflammation and endothelialization. Conclusion ApoA-I antibody coating has potent pro-endothelial and anti-thrombotic effects in vitro, but failed to enhance stent performance in a balloon injury rabbit model in vivo.

Background— Coronary guidewires are indispensable during percutaneous coronary interventions. Nowadays, most guidewires have hydrophilic coatings to improve their trackability, allowing easy lesion passage and facilitating balloon and stent positioning. Recent reports, however, have raised concerns about detachment and subsequent embolization of these hydrophilic coatings. Methods and Results— We have retrospectively reviewed the histological samples of the myocardium, obtained during autopsies in the period 2009 to 2013, from all patients who had a history of percutaneous coronary interventions (n=40). Foreign material was observed in the distal myocardium in 4 patients (10%). Furthermore, we have reviewed 205 thrombus specimens which were obtained during thrombus aspiration in the setting of primary percutaneous coronary interventions in the period 2005 to 2009. In 45% of the cases, foreign material was observed within the thrombus. Finally, we have examined the histopathologic appearance of hydrophilic-guidewire coating material ex vivo by embedding the coating in placenta specimen and cut and stain it in exactly the same manner as the myocardium and thrombus specimen. The histopathologic appearance of the hydrophilic coating ex vivo was identical to the foreign material found in vivo. Conclusions— Distal embolization of hydrophilic-coating material was observed in 10% of the patients who had a history of percutaneous coronary interventions. Hydrophilic-coating material was found in 45% of coronary thrombus specimen obtained during thrombus aspiration. These findings suggest that detachment and distal embolization of hydrophilic-coating material from coronary guidewires occur more often than the sparse literature on this topic suggests.

Contains fulltext : 154718.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cor triatriatum is a rare congenital cardiac abnormality, consisting of an obstructing membrane between the pulmonary veins and the mitral valve in varying patterns. The entitiy can mimick the pathophysiology of mitral stenosis, necessitating surgical resection. Occasionally, percutaneous balloon dilatation of the membrane has been successfully performed. CASE PRESENTATION: We report two cases with cor triatriatum where intraoperative balloon dilatation of the membrane was attempted followed by surgical resection, to explore the feasibility of cathether-based interventional strategies for cor triatriatum. CONCLUSIONS: Various anatomical variations exist of cor triatriatum, depending on the drainage of the pulmonary veins and the drainage of the proximal chamber in the right or left atrium. Only isolated forms of cor triatriatum where all pulmonary veins ultimately drain into the left atrium can be recommended for percutaneous strategies. In addition, several anatomical characteristics should be considered to predict technical success of cathether-based interventional strategies, such as the location of the membrane, the degree of pulmonary vein stenosis, the extent of calcification, and the presence of other (congenital) cardiovascular abnormalities. Furthermore, long-term efficacy of these strategies remains to be confirmed. As such, surgical treatment of cor triatriatum remains the mainstay of treatment in adult patients, especially when other cardiovascular anomalies are present which require surgical correction.

Hybrid coronary revascularization (HCR) combines a surgical and percutaneous approach for treatment of multivessel coronary artery disease. A survey was conducted among 200 cardiologists and cardiac surgeons from 100 top-ranked US hospitals. Questions were asked involving the perception, experience, and future expectations of HCR. Of physicians invited to the survey, 90 completed the survey (45.5%). Relative to nonresponders, responders were more often affiliated with an academic institution (80.0% vs 61.8%, P=.005), with higher patient volumes, and with the availability of a hybrid operating room (90.0% vs 67.3%, P

Smooth muscle cells, macrophage infiltration and accumulation of lipids, proteoglycans, collagen matrix and calcification play a central role in atherosclerosis. The early histologic changes of plaque progression from pathologic intimal thickenings (PIT) to late fibroatheroma lesions have not been fully characterized. A total of 151 atherosclerotic coronary lesions were collected from 67 sudden death victims. Atherosclerotic plaques were classified as PIT without macrophage infiltration, PIT with macrophages, and early and late fibroatheromas. Presence of macrophages and proteoglycans (versican, decorin and biglycan) were recognized by specific antibodies while hyaluronan was detected by affinity histochemistry. Lipid deposition was identified by oil-red-O, and calcification was assessed following von Kossa and alizarin red staining. Lesion progression from PIT to late fibroatheroma was associated with increase in macrophage accumulation (p < 0.001) and decreasing apoptotic body clearance by macrophages (ratio of engulfed-to-total apoptotic bodies) (p < 0.001). Lipid deposition in lipid pool of PIT had a microvesicular appearance whereas those in the necrotic core were globular in nature. Overall, the accumulation of hyaluronan (p < 0.001), and proteoglycan versican (p < 0.001) and biglycan (p = 0.013) declined along with lesion progression from PIT to fibroatheromas. Microcalcification was first observed only within areas of lipid pools and its presence and size increased in lesions with necrotic core. PIT to fibroatheroma lesions are accompanied by early lipid accumulation, followed by macrophage infiltration with defective clearance of apoptotic bodies along with decrease in proteoglycan and hyaluronan in lipid pools that convert to necrotic cores. Calcification starts in PIT and increases with plaque progression

AIMS To report procedural and midterm clinical outcomes after the use of the second-generation Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) in a real-world percutaneous coronary intervention (PCI) registry. METHODS AND RESULTS All patients assigned to treatment with the Absorb BVS in the Academic Medical Center, Amsterdam, between August 2012 and August 2013 were included in a prospective registry. A total of 135 patients were included in the study, including 53 (39%) acute coronary syndrome (ACS) patients (13% ST-segment elevation myocardial infarction [STEMI]). In total 159 lesions were treated, including 102 (62%) with a type B2 or C classification. Pre- and post-procedural quantitative coronary angiography (QCA) analyses showed an acute gain of 1.37±0.53 mm. An angiographic success rate was achieved in 152 (96%) of the lesions. Six-month follow-up was available in 97% of the patients. Six-month cumulative target vessel failure (composite of all-cause mortality, any myocardial infarction [MI] and target vessel revascularisation [TVR]) rate was 8.5%, including a 3.0% MI, 3.0% definite scaffold thrombosis, 6.3% target lesion revascularisation, and an 8.5% TVR rate. CONCLUSIONS The use of the Absorb BVS in a cohort reflecting daily clinical practice is feasible and associated with good procedural safety and angiographic success rate. In addition, six-month follow-up is associated with acceptable clinical outcomes.

Aims The Tryton bifurcation stent has been developed to improve clinical outcomes after treatment of bifurcation lesions. Limited data are available on the use of the Absorb bioresorbable vascular scaffold (BVS) in bifurcation lesions with side branches >2 mm. We present here the acute procedural results and midterm clinical follow-up of the first-in-man combined use of the Tryton stent and the Absorb scaffold for the treatment of complex bifurcation lesions. Methods and results Ten patients treated with the Tryton stent in combination with Absorb BVS were included in the current report. Offline two- and three-dimensional optical coherence tomography (OCT) analyses were performed to gain more insights into this novel approach. Procedural success was 91%, whereas angiographic success was achieved in 82%. Two TLRs occurred (TLR rate 20%), whereas no deaths, myocardial infarctions or stent thromboses were observed up to six months of follow-up. Conclusions We present a new treatment strategy in complex bifurcation lesions using the Tryton stent in combination with the Absorb BVS. This approach potentially offers an opportunity to treat complex bifurcation lesions with the Absorb BVS. Furthermore, three-dimensional OCT reconstructions give valuable insights into PCI of complex bifurcation lesions.

Background Early reperfusion of ischemic myocytes is essential for optimal salvage in acute myocardial infarction. VA (ventricular arrhythmia) bursts after recanalization of the culprit vessel have been found to be related to larger infarct size (IS), using SPECT. Objective The hypothesis was tested that this finding could be confirmed in an independent cohort using a more accurate technique, i.e. delayed-enhancement cardiovascular magnetic resonance imaging (DE-CMR). Methods All 196 patients from the PREPARE and MAST studies who had 24-hour, continuous, 12-lead Holter, started before primary percutaneous coronary intervention resulting in brisk TIMI (thrombolysis in myocardial infarction) 3 flow and stable ST-recovery were included. VA bursts were identified against subject-specific background VA rates using a previously published statistical outlier method. IS was assessed using DE-CMR. Angiography, Holter and DE-CMR results were assessed in core laboratories, blinded to all other data. Results VA bursts were present in 154/196 (79%) of patients. Baseline characteristics between the groups with and without bursts were similar. VA burst was associated with significantly larger infarct size in the population as a whole (median 11.3% vs 5.3%; p=0.001) and also when divided in non-anterior (median 9.9% vs 4.9%; p=0.003) and anterior myocardial infarction (median 21.4% vs 12.0%; p=0.48), the latter not reaching statistical significance due to the small subset of patients. Conclusion Beyond the classical markers of "optimal" reperfusion such as TIMI 3 flow and stable ST-segment recovery, VA bursts occurring during the reperfusion phase are an early electrobiomarker of larger IS. Clinical trial registration: PREPARE: ISRCTN71104460 http://www.controlled-trials.com/ISRCTN71104460.

Distinct stressors may induce heart failure. As compensation, β-adrenergic stimulation enhances myocardial contractility by elevating cardiomyocyte intracellular Ca2+ ([Ca2+]i). However, chronic β-adrenergic stimulation promotes adverse cardiac remodelling. Cardiac expression of nuclear receptor Nur77 is enhanced by β-adrenergic stimulation, but its role in cardiac remodelling is still unclear. We show high and rapid Nur77 upregulation in cardiomyocytes stimulated with β-adrenergic agonist isoproterenol. Nur77 knockdown in culture resulted in hypertrophic cardiomyocytes. Ventricular cardiomyocytes from Nur77-deficient (Nur77-KO) mice exhibited elevated diastolic and systolic [Ca2+]i and prolonged action potentials compared to wild type (WT). In vivo, these differences resulted in larger cardiomyocytes, increased expression of hypertrophic genes and more cardiac fibrosis in Nur77-KO mice upon chronic isoproterenol stimulation. In line with the observed elevated [Ca2+]i, Ca2+-activated phosphatase calcineurin was more active in Nur77-KO mice compared to WT. In contrast, after cardiac pressure overload by aortic constriction, Nur77-KO mice exhibited attenuated remodelling compared to WT. Concluding, Nur77-deficiency results in significantly altered cardiac Ca2+ homeostasis and distinct remodelling outcome depending on the type of insult. Detailed knowledge on the role of Nur77 in maintaining cardiomyocyte Ca2+ homeostasis and the dual role Nur77 plays in cardiac remodelling will aid in developing personalized therapies against heart failure.

In acute ST-elevation myocardial infarction (STEMI), patients with multivessel disease (MVD) are considered to be a subgroup with an increased risk of mortality compared with patients with single-vessel disease (SVD). To evaluate the effect of MVD on 1-year mortality in patients with STEMI, we studied 1,417 consecutive patients with STEMI who were admitted between 1997 and 2002 and treated with primary percutaneous coronary intervention. Further, we hypothesized that the effect of MVD on mortality is due to the presence of a chronic total occlusion in a noninfarct-related artery. Patients with MVD and/or a chronic total occlusion had multiple differences in baseline and angiographic characteristics that were associated with worse outcome. Mortalities in patients with SVD, MVD, and a chronic total occlusion were 8%, 16%, and 35%, respectively. After correction for the baseline differences, MVD was an independent predictor of mortality (odds ratio 1.5, 95% confidence interval 1.1 to 2.1). However, when chronic total occlusion was included in the model, MVD was no longer an independent predictor for mortality, whereas chronic total occlusion was a strong and independent predictor for 1-year mortality in patients with STEMI treated with percutaneous coronary intervention (odds ratio 3.8, 95% confidence interval 2.5 to 5.8). In conclusion, patients with STEMI and MVD have a higher 1-year mortality rate compared with patients with SVD, which is mainly determined by the presence of a chronic total occlusion in a noninfarct-related artery. In the setting of primary percutaneous coronary intervention, the presence of a chronic total occlusion, and not the mere presence of MVD, is an independent predictor of mortality.

Background: Platelet-derived microparticles (PMPs) are generally considered a marker of platelet activation in cardiovascular disease. We studied the extent to which PMP subpopulations parallel platelet activation in vitro and in vivo. Methods: Using flow cytometry, we analyzed PMP subpopulations from resting and activated platelets in vitro (n = 6) as well as from plasma samples of patients with stable angina, peripheral arterial disease, or myocardial infarction [non-ST-elevation (NSTEMI) and ST-elevation (STEMI)] and from older, age- and sex-matched and young healthy individuals [n = 10 for all groups except NSTEMI (n = 11)]. Coagulation markers prothrombin fragment F1 + 2 and thrombin-antithrombin complexes were determined by ELISA. The PMP-associated fraction of soluble (s)P-selectin was estimated by ELISA. Results: In vitro, stimulation of platelets with thrombin receptor–activating peptide (15 μmol/L) or the calcium ionophore A23187 (2.5 μmol/L) increased fractions of both platelets and PMPs exposing P-selectin or CD63 (P 0.05). Ex vivo, numbers of circulating PMPs were comparable in all groups. Compared with young persons, P-selectin–exposing PMPs were increased in older persons (P = 0.02) and were further increased in patients with NSTEMI (P = 0.007) and STEMI (P = 0.045). CD63-exposing PMPs were increased in patients with peripheral arterial disease (P = 0.041), NSTEMI (P = 0.001), and STEMI (P = 0.049). Subpopulations exposing P-selectin or CD63 correlated with each other (r = 0.581; P Conclusions: PMP subpopulations reflect platelet activation status better than the total number of PMPs. Increased concentrations of circulating PMP subpopulations are found in aging, and further increases are encountered in peripheral arterial disease and myocardial infarction.

Previous studies have suggested that coronary flow velocity reserve (CFVR) in the early phase of acute myocardial infarction (AMI) is abnormal in infarcted and remote regions. This study determined the coronary microvascular resistance of infarct-related arteries (IRAs) and non-IRAs during AMI and at follow-up in patients who were treated with primary percutaneous intervention. In 73 patients with a first anterior wall AMI, baseline and minimal microvascular resistance in IRAs and non-IRAs immediately after reperfusion and at 1-week and 6-month follow-up were calculated as the ratio of mean transvascular pressure gradient to mean baseline and to adenosine-induced hyperemic blood flow velocity, respectively. CFVR in IRAs increased from 1.6 +/- 0.4 after reperfusion to 1.9 +/- 0.5 at 1 week and to 3.0 +/- 0.8 at 6 months (p