The Viennese EDDY Study as a Role Model for Obesity: Prevention by Means of Nutritional and Lifestyle Interventions.

OBJECTIVES: Obesity in children and adolescents is a worldwide dramatic health problem, for which treatment is mostly unsuccessful. Therefore, prevention is the most important measure to tackle this problem. The 'EDDY' study as an interventional cohort study with a 1-year lifestyle intervention aimed to affect the lifestyle and nutrition habits of adolescents by intervention with nutritional training and sports programs to prevent obesity. METHODS: Four Viennese schools were cluster-randomized into an intervention group and a control group. A total of 141 pupils aged 11-14 years were included. The intervention group received a comprehensive, age-appropriate training on nutrition and lifestyle exercise intervention for 12 months. Before and after intervention and at two follow-ups, subjects were anthropometrically measured. In addition, knowledge of nutritional issues and eating habits were measured with questionnaires. RESULTS: The data imply an improvement of nutrition knowledge, a significant reduction in the consumption of junk food (p = 0.01), sweets (p = 0.001) and salty snacks (p < 0.001) as well as a slight improvement of physical performance after intervention. Although there was a trend for a less increase of body fat in the intervention group, no significant changes could have been shown in the anthropometric data. CONCLUSIONS: An age-adjusted lifestyle intervention based on dietary training and exercise can improve the nutritional knowledge and eating habits of school children.

In vivo cardiac role of migfilin during experimental pressure overload.

AIMS: Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear. METHODS AND RESULTS: To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload. CONCLUSIONS: Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC.

Sex differences in independent factors associated with coronary artery disease.

BACKGROUND: Women undergoing coronary angiography (CA) due to chest pain are more likely to present with less extensive coronary artery disease (CAD) than men, which might be attributed to different effects of cardiovascular risk factors on coronary atherogenesis between sexes. The aim of the present study was to evaluate sex differences in independent factors associated with obstructive and non-obstructive CAD in a large consecutive cohort of patients undergoing elective CA. METHODS: Data from 7819 patients (2653 women and 5184 men), including cardiovascular risk factors, clinical presentation, CAD severity and treatment decisions were analysed. RESULTS: Women were older than men (65 ± 11 vs. 63 ± 11 years, p < 0.001); low-density lipoprotein cholesterol (LDL; 125 ± 38 vs. 122 ± 37 mg/dL, p < 0.001) and high-density lipoprotein cholesterol (HDL) cholesterol levels (62 ± 18 vs. 51 ± 15 mg/dL, p < 0.001) were higher in women; and smokers were more frequently men (14.4 vs. 20.1%, p < 0.001). Men more frequently had an obstructive CAD (41.1 vs. 65.6%, p < 0.001). Multivariable analyses revealed age, HDL cholesterol, hypercholesterolaemia, diabetes mellitus, arterial hypertension and a positive family history being associated with obstructive CAD in both sexes, whereas smoking was independently associated with obstructive CAD only in women. The association of hypercholesterolaemia with obstructive CAD was stronger in men. For non-obstructive CAD, no sex-specific associated factors could be identified. CONCLUSION: The impact of smoking and hypercholesterolaemia on coronary atherosclerosis is different between women and men. This might be taken into account when planning individual interventions to reduce cardiovascular risk.

The angiogenic factor secretoneurin induces coronary angiogenesis in a model of myocardial infarction by stimulation of vascular endothelial growth factor signaling in endothelial cells.

BACKGROUND: Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endothelial cells. METHODS AND RESULTS: In vivo secretoneurin improved left ventricular function, inhibited remodeling, and reduced scar formation. In the infarct border zone, secretoneurin induced coronary angiogenesis, as shown by increased density of capillaries and arteries. In vitro secretoneurin induced capillary tubes, stimulated proliferation, inhibited apoptosis, and activated Akt and extracellular signal-regulated kinase in coronary endothelial cells. Effects were abrogated by a vascular endothelial growth factor (VEGF) antibody, and secretoneurin stimulated VEGF receptors in these cells. Secretoneurin furthermore increased binding of VEGF to endothelial cells, and binding was blocked by heparinase, indicating that secretoneurin stimulates binding of VEGF to heparan sulfate proteoglycan binding sites. Additionally, secretoneurin increased binding of VEGF to its coreceptor neuropilin-1. In endothelial cells, secretoneurin also stimulated fibroblast growth factor receptor-3 and insulin-like growth factor-1 receptor, and in coronary vascular smooth muscle cells, we observed stimulation of VEGF receptor-1 and fibroblast growth factor receptor-3. Exposure of cardiac myocytes to hypoxia and ischemic heart after myocardial infarction revealed increased secretoneurin messenger RNA and protein. CONCLUSIONS: Our data show that secretoneurin acts as an endogenous stimulator of VEGF signaling in coronary endothelial cells by enhancing binding of VEGF to low-affinity binding sites and neuropilin-1 and stimulates further growth factor receptors like fibroblast growth factor receptor-3. Our in vivo findings indicate that secretoneurin may be a promising therapeutic tool in ischemic heart disease.

Prasugrel vs. ticagrelor in acute coronary syndromes: which one to choose?

Acute coronary syndromes (ACS) are still associated with significant morbidity and mortality. Dual antiplatelet therapy with clopidogrel and acetyl-salicylic acid has become the standard of care for patients with ACS in the last 2 decades. However, clopidogrel has drawbacks including delayed therapeutic effect, significant interindividual variability of platelet aggregation inhibition or reduced action on thrombocytes due to interaction with other drugs or genetic polymorphisms. Consequently, new antiplatelet drugs have been developed. Two of these drugs, namely prasugrel and ticagrelor, have been approved by the European Medicines Agency (EMA) and are already available in many European countries. For each substance a "mega-trial" has been published. Both agents were clearly superior compared to clopidogrel and should be therefore preferred in patients with ACS. However, no study has directly compared efficacy as well as safety of prasugrel and ticagrelor so far. Hence, clinicians will be claimed to decide which one to choose in everyday practice. The aim of this manuscript is to summarize the current literature and to provide a guide for individual decision-making between prasugrel and ticagrelor in ACS in daily routine.

Major risk stratification models do not predict perioperative outcome after coronary artery bypass grafting in patients with previous percutaneous intervention.

OBJECTIVE: To investigate whether common risk stratification models in cardiac surgery predict perioperative outcome of coronary artery bypass grafting (CABG) in patients with previous percutaneous coronary interventions (PCIs). METHODS: We retrospectively analyzed the perioperative mortality and morbidity of 367 patients with prior elective PCI versus 2361 patients without prior PCI, who underwent first-time isolated CABG between 2001 and 2009 at our institution. Receiver operating characteristics (ROC) were used to describe the performance and accuracy of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and the Society of Thoracic Surgeons (STS) risk model in predicting mortality and morbidity. RESULTS: Both groups were comparable concerning preoperative logistic EuroSCORE (PCI: 4.9 ± 6.57, non-PCI: 4.60 ± 5.45, p=0.51). Patients with previous elective PCI had increased perioperative mortality (PCI: 3.8% vs non-PCI: 2.1%, p=0.01) and higher rates of major adverse cardiac events (8.4% vs 4.5% respectively, p=0.003). Discriminatory power for 30-day mortality was higher in the non-PCI group (EuroSCORE area under the curve (AUC): 0.875 vs 0.552 in the PCI group). Logistic EuroSCORE predicted 30-day mortality in the non-PCI group (confidence interval (CI)=0.806-0.934, p=0.0004) but not in the PCI group (CI=0.301-0.765, p=0.8). Discriminatory power for morbidity or mortality (M&M) was lower in the PCI group (AUC: 0.980 vs 0.713 for the non-PCI group). The STS risk model had a lower discriminatory power for predicting M&M in PCI patients (AUC: 0.611 vs 0.686 for the non-PCI group, p<0.001). CONCLUSIONS: The EuroSCORE and the STS risk model were inaccurate in predicting perioperative mortality after CABG in patients with history of elective PCI. There is a need for modification of risk models to improve risk assessment for surgical candidates with prior PCI.

Comparison of peripheral endothelial function in shift versus nonshift workers.

Shift working is related to increased cardiovascular morbidity. Peripheral endothelial dysfunction, an inherent feature of early atherosclerosis, has been suggested as a surrogate marker of cardiovascular risk. Whether shift working is associated with peripheral endothelial dysfunction has not been investigated to date. A total of 48 male shift workers (SWs) and 47 male nonshift workers (NSWs) (mean age 43 ± 5 years) were recruited from a glass manufactory. The SWs and NSWs were matched according to age, body mass index, smoking habits, family history of premature coronary artery disease, prevalence of hypercholesterolemia and hypertension, and work place. Their sport habits were also documented. Peripheral endothelial function was assessed using the EndoPAT technique to determine the peripheral arterial tone (PAT) index. According to the study design, no difference was found in the risk factor profiles between the SWs and NSWs. Despite a greater percentage of regular physical activity among the SWs (16.7 vs 4.3%, p = 0.05), shift working was associated with a reduced PAT index compared to working only on the day shift (PAT index 1.73 ± 0.4 vs 1.94 ± 0.5, p = 0.03). In the NSW group, the participants with regular physical training (n = 16) had a greater PAT index than those without regular physical activity (n = 12; PAT index 2.28 ± 0.45 vs 1.86 ± 0.51, p = 0.03). No such difference was found in the SWs. In conclusion, SWs had a reduced PAT index compared with NSWs, suggesting endothelial dysfunction. Therefore, the known increased cardiovascular risk in those shift working might be related to endothelial dysfunction.

[Biomarker for diagnosis of rejection after heart transplantation]. / Biomarker zur Diagnose der zellulären Abstossung nach Herztransplantation.

Heart transplantation is an established therapeutic modality in patients with end-stage heart failure. In the 1st year after transplantation acute cellular rejection is still important. The diagnosis of acute cellular rejection is based on the histological evaluation of endomyocardial biopsy (EMB) specimens. EMB is an invasive procedure with a definite risk and poor tolerance in some patients. Imaging methods like echocardiography and magnetic resonance imaging as well as intracardiac ECG have been used for noninvasive diagnosis of acute cellular rejection. In addition, a large number of circulating biomarkers have been evaluated for noninvasive diagnosis of rejection. B-type natriuretic peptide, troponin and inflammatory markers are the most important biomarkers in this field. Although these parameters are useful, none of them has the potential to replace EMB as the gold standard for diagnosis of rejection. In the near future microarray technology might get important for diagnosis of acute cellular rejection. Using microarray technique gene expression profiles can be detected, which are associated with an increased risk for rejection. Ongoing studies will demonstrate, whether microarrays can at least reduce the number of EMBs.

PI3Kgamma protects from myocardial ischemia and reperfusion injury through a kinase-independent pathway.

BACKGROUND: PI3Kgamma functions in the immune compartment to promote inflammation in response to G-protein-coupled receptor (GPCR) agonists and PI3Kgamma also acts within the heart itself both as a negative regulator of cardiac contractility and as a pro-survival factor. Thus, PI3Kgamma has the potential to both promote and limit M I/R injury. METHODOLOGY/PRINCIPAL FINDINGS: Complete PI3Kgamma-/- mutant mice, catalytically inactive PI3KgammaKD/KD (KD) knock-in mice, and control wild type (WT) mice were subjected to in vivo myocardial ischemia and reperfusion (M I/R) injury. Additionally, bone-marrow chimeric mice were constructed to elucidate the contribution of the inflammatory response to cardiac damage. PI3Kgamma-/- mice exhibited a significantly increased infarction size following reperfusion. Mechanistically, PI3Kgamma is required for activation of the Reperfusion Injury Salvage Kinase (RISK) pathway (AKT/ERK1/2) and regulates phospholamban phosphorylation in the acute injury response. Using bone marrow chimeras, the cardioprotective role of PI3Kgamma was mapped to non-haematopoietic cells. Importantly, this massive increase in M I/R injury in PI3Kgamma-/- mice was rescued in PI3Kgamma kinase-dead (PI3KgammaKD/KD) knock-in mice. However, PI3KgammaKD/KD mice exhibited a cardiac injury similar to wild type animals, suggesting that specific blockade of PI3Kgamma catalytic activity has no beneficial effects. CONCLUSIONS/SIGNIFICANCE: Our data show that PI3Kgamma is cardioprotective during M I/R injury independent of its catalytic kinase activity and that loss of PI3Kgamma function in the hematopoietic compartment does not affect disease outcome. Thus, clinical development of specific PI3Kgamma blockers should proceed with caution.

[Myocarditis and sudden cardiac death in athletes. Diagnosis, treatment, and prevention]. / Myokarditis als Ursache des plötzlichen Herztodes bei Sportlern. Diagnose, Behandlung und Prävention.

Myocarditis is the reason for sudden cardiac death in 5-22% of athletes < 35 years of age. Actually, parvovirus B19 and human herpes virus 6 are the most important pathogens. Clinical presentation of myocarditis is heterogeneous, with all courses between asymptomatic and fulminant reported. Especially in athletes it is important to take subtle discomforts seriously and initiate further evaluation. Electrocardiogram, laboratory parameters, serologic markers, and echocardiography are helpful in diagnosis of myocarditis, but are not specific. Magnetic resonance imaging (MRI) of the heart has become an important tool in the evaluation of patients with myocarditis and allows noninvasive appraisal of myocardial inflammation using late enhancement. However, MRI is not able to assess viral persistence. Therefore, endomyocardial biopsy (EMB) remains the gold standard in diagnosis of myocarditis. When considering EMB in these athletes one should not ignore spontaneous healing in 50% of patients with myocarditis. Contrariwise, specific therapy (e.g., immunosuppression, interferon, immunoglobulins) for myocarditis is only feasible after getting results of EMB. When myocarditis is verified, athletes have to withdraw from sport for at least 6 months. Before restarting physical activity, a detailed examination is necessary and most of the patients will undergo another EMB. For prevention of myocarditis and sudden cardiac death it is recommended to stop elite sport for 4 weeks after an unspecific infection. Whether moderate sport can be started earlier is unclear.

Increased mortality and perioperative complications in patients with previous elective percutaneous coronary interventions undergoing coronary artery bypass surgery.

OBJECTIVE: The relationship between previous percutaneous coronary intervention and perioperative outcome after coronary artery bypass grafting remains undetermined. The aim of the study was to investigate whether previous elective percutaneous coronary intervention influences the outcome of elective coronary artery bypass grafting. METHODS: Between 2002 and 2007, 4412 consecutive patients underwent first-time open surgery at the Innsbruck Medical University. After excluding patients with a history of emergency percutaneous coronary intervention, we isolated 306 patients with elective percutaneous coronary intervention during the last 24 months before isolated coronary artery bypass grafting (group 1). Those patients were compared with 452 consecutive age-, gender-, and EuroSCORE-matched patients without a history of percutaneous coronary intervention (group 2), in terms of 30-day mortality, major adverse cardiac events, and perioperative complications. RESULTS: Both groups were comparable concerning preoperative linear EuroSCORE (group 1: 4.83 +/- 0.18, group 2: 4.72 +/- 0.14, P = .63). Patients who underwent previous elective percutaneous coronary intervention before coronary artery bypass grafting had an increase in perioperative mortality (group 1: 4.4% vs group 2: 2.4%, P < .001) and major adverse cardiac events (group 1: 7.9% vs 4.3%, P < .001). In addition, the incidence of bleeding complications (group 1: 5.9% vs group 2: 3.8%, P = .017) and the number of blood products (group 1: 1.70 +/- 0.31 vs 0.61 +/- 0.17, P < .001) used were higher in patients of group 1. A higher incidence of acute renal failure (5.9% vs 2.7%, P = .025) and renal replacement therapy (3.6% vs 1.7%, P = .03) was observed in patients of group 1. CONCLUSION: Patients with a history of elective percutaneous coronary intervention before referral to coronary artery bypass grafting have a worse perioperative outcome in terms of mortality, major adverse cardiac events, and perioperative complications compared with patients without a history of percutaneous coronary intervention. This fact should be considered in risk stratification for patients who are scheduled for elective coronary artery bypass grafting.

Neopterin, CD4+CD28- lymphocytes and the extent and severity of coronary artery disease.

OBJECTIVES: Macrophages and pro-inflammatory CD3+CD4+CD28- T lymphocytes are involved in atherosclerotic plaque destabilization. Whether neopterin, a macrophage-specific activation-marker, and circulating CD3+CD4+CD28- cells are also related to the severity and extent of coronary artery disease (CAD) in stable patients is still unclear. METHODS: Coronary angiograms of 30 patients with stable angina pectoris were graded using the Gensini severity and an extent score. Patients were grouped according to the median of each score. Lymphocyte subsets were determined by FACS analysis and neopterin by radioimmunoassay. Peripheral endothelial function of the brachial artery (FMD) shown to correlate with cardiovascular risk factors was evaluated using high-resolution ultrasound. RESULTS: More extensive CAD was associated with increased neopterin levels (8.3 +/- 3.3 vs. 5.5 +/- 1.2 nmol/L, p < 0.001) and increased CD3+CD4+CD28- cells (3.1 +/- 1.6 vs. 2.0 +/- 1.2%, p < 0.05). A high Gensini severity score was associated with increased neopterin levels (7.8 +/- 2.7 vs. 6.3 +/- 1.7 nmol/L, p < 0.05), but not with CD3+CD4+CD28- cells. Neopterin correlated with both the extent (r = 0.59, p < 0.001) and the Gensini score (r = 0.57, p < 0.003). FMD was not correlated with both scores. CONCLUSIONS: Neopterin and CD3+CD4+CD28- lymphocytes are associated with CAD extent in stable patients, thereby emphasizing the inherent role of inflammation in atherogenesis itself beyond plaque destabilization. Neopterin's correlation with CAD severity might be additionally useful in identifying patients eligible for revascularization procedures.

Lack of association of soluble CD40 ligand with the presence of acute myocardial infarction or ischemic stroke in the emergency department.

BACKGROUND: Soluble CD40 ligand (sCD40L) has been proposed as a new risk marker for cardiovascular diseases; however, its possible role as a diagnostic marker in the emergency department (ED) has not yet been investigated. METHODS: We investigated sCD40L for the diagnosis of acute myocardial infarction or ischemic stroke in 1089 consecutive patients (525 males, 564 females; age, 17-98 years; median, 56 years) in an ED treating mainly adults with medical or neurologic emergencies. We used a research assay from Roche Diagnostics to measure sCD40L in heparinized plasma prepared from routinely drawn blood samples. RESULTS: Intraassay and interassay CVs in our laboratory ranged from 1.6%-4.2% and from 4.4%-4.9%, respectively. A multiple linear regression analysis revealed sCD40L concentration to be significantly associated with C-reactive protein concentration (P = 0.012) and platelet count (P < 0.001). In addition, a subgroup analysis revealed a significant association between smoking and sCD40L concentration (P = 0.006). All other tested variables, including discharge diagnosis, age, sex, and other laboratory variables, showed no significant associations. CONCLUSIONS: In adults presenting to the ED, sCD40L is not useful as a diagnostic marker for acute cardiac, cerebrovascular ischemic, or thromboembolic events.

Prognosis and risk factors in patients with asymptomatic aortic stenosis and their modulation by atorvastatin (20 mg).

The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 +/- 1.2 years. Patients' prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal-pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.

Value of transesophageal 3D echocardiography as an adjunct to conventional 2D imaging in preoperative evaluation of cardiac masses.

BACKGROUND: This study sought to compare three-dimensional (3D) and two-dimensional (2D) transesophageal echocardiography (TEE) to assess intracardiac masses. It was hypothesized that 3D TEE would reveal incremental information for surgical and nonsurgical management. METHODS: In 41 patients presenting with intracardiac masses (17 thrombi, 15 myxomas, 2 lymphomas, 2 caseous calcifications of the mitral valve and one each of hypernephroma, hepatocellular carcinoma, rhabdomyosarcoma, lipoma, and fibroelastoma), 2D and 3D TEE were performed, aiming to assess the surface characteristics of the lesions, their relationship to surrounding structures, and attachments. Diagnoses were made by histopathology (n = 28), by computed tomography (n = 8), or by magnetic resonance imaging (n = 5). Benefit was categorized as follows: (A) New information obtained through 3D TEE; (B) helpful unique views but no additional findings compared to 2D TEE; (C) results equivalent to 2D TEE; (D) 3D TEE missed 2D findings. RESULTS: In 15 subjects (37%), 3D TEE revealed one or more items of additional information (category A) regarding type and site of attachment (n = 9, 22%), surface features (n = 6, 15%), and spatial relationship to surrounding structures (n = 8, 20%). In at least 18% of all intracardiac masses, 3D TEE can be expected to deliver supplementary information. In six patients, additional findings led to decisions deviating from those made on the basis of 2D TEE. In 11 subjects (27%), 3D echocardiographic findings were categorized as "B." CONCLUSIONS: Information revealed by 3D imaging facilitates therapeutic decision making and especially the choice of an optimal surgical access prior to removal of intracardiac masses.

Drug-eluting or bare-metal stents for large coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: study protocol and design.

BACKGROUND: Based on a subgroup analysis of 18-month BAsel Stent Kosten Effektivitäts Trial (BASKET) outcome data, we hypothesized that very late (> 12 months) stent thrombosis occurs predominantly after drug-eluting stent implantation in large native coronary vessel stenting. METHODS: To prove or refute this hypothesis, we set up an 11-center 4-country prospective trial of 2260 consecutive patients treated with > or = 3.0-mm stents only, randomized to receive Cypher (Johnson & Johnson, Miami Lakes, FL), Vision (Abbott Vascular, Abbott Laboratories, IL), or Xience stents (Abbott Vascular). Only patients with left main or bypass graft disease, in-stent restenosis or stent thrombosis, in need of nonheart surgery, at increased bleeding risk, without compliance/consent are excluded. All patients are treated with dual antiplatelet therapy for 12 months. The primary end point will be cardiac death/nonfatal myocardial infarction after 24 months with further follow-up up to 5 years. RESULTS: By June 12, 229 patients (10% of the planned total) were included with a baseline risk similar to that of the same subgroup of BASKET (n = 588). CONCLUSIONS: This study will answer several important questions of contemporary stent use in patients with large native vessel stenting. The 2-year death/myocardial infarction-as well as target vessel revascularization-and bleeding rates in these patients with a first- versus second-generation drug-eluting stent should demonstrate the benefit or harm of these stents compared to cobalt-chromium bare-metal stents in this relevant, low-risk group of everyday patients. In addition, a comparison with similar BASKET patients will allow to estimate the impact of 12- versus 6-month dual antiplatelet therapy on these outcomes.

Myocardial ischaemia-reperfusion injury in haematopoietic cell-restricted beta1 integrin knockout mice.

Evidence indicates that the intercellular adhesion molecule-1 and its counter-receptor beta2 integrin are cardioprotective proteins during myocardial ischaemia-reperfusion, but no data are available concerning the role of blood cell beta1 integrins in this process. We studied the effects of temporary myocardial ischaemia and reperfusion in blood cell-restricted beta1 integrin knockout mice (beta1(-/-)). The left descending coronary artery in conditional beta1(-/-) integrin (beta1(-/-)), beta1 integrin +/+ (beta1(+/+)) and beta1 integrin -/- bone marrow chimeric (beta1(-/-) BM) mice was ligated for 30 min, followed by reperfusion of either 3 h or 3 weeks. Plasma levels of troponin T were evaluated as an index of cardiac cellular damage. The histological evaluation of tissue damage was performed with Haematoxylin and Eosin stained sections. Cell infiltrations in the ischaemic area were investigated by immunofluorescence studies. It was found that plasma troponin T was at a similar level in beta1(-/-), beta1(+/+) and beta1(-/-) BM mice treated with 30 min ischaemia and 3 h reperfusion. Histological analysis showed that ischaemia-reperfusion resulted in marked myocardial injury in all groups of animals, but the damage score of the hearts was not significantly different between beta1(-/-), beta1(+/+) and beta1(-/-) BM mice after 3 h of reperfusion following 30 min of ischaemia (2.8 +/- 0.5, 2.6 +/- 0.5 and 2.8 +/- 0.6, respectively, n.s.). Furthermore, no difference in scar sizes in ischaemia-injured hearts was found 3 weeks after ischaemia. Semi-quantification of cells demonstrated that, compared with beta1(+/+) mice, the number of infiltrating neutrophils was significantly reduced in beta1(-/-) and beta1(-/-) BM mice, whereas MAC-1(CD11b/CD18)-positive cells in the ischaemic regions were similar in myocardial tissues of all groups. We conclude that absence of beta1 integrin expression in haematopoietic cells results in reduced neutrophil infiltration in the ischaemic regions, but does not influence myocardial damage of ischaemic hearts.

Single-plane balloon sizing of atrial septal defects with intracardiac echocardiography: an advantageous alternative to fluoroscopy.

OBJECTIVE: We sought to evaluate intracardiac echocardiography (ICE) in comparison with transesophageal echocardiography and fluoroscopy for sizing of atrial septal defects (ASDs). METHODS: In 43 patients (mean age 40 +/- 15 years) with ASD, the native defect size was measured by transesophageal echocardiography and ICE. On subsequent balloon sizing, the stretched balloon diameter was measured by both fluoroscopy in two perpendicular planes and by ICE in just a single standard cut plane. RESULTS: All ASDs were successfully closed with Amplatzer occluders (AGA Medical Corp., Plymouth, Minn). Conventional fluoroscopy-based balloon sizing revealed diameters of 17.5 +/- 5.4 mm, transesophageal echocardiography diameters of 11.8 +/- 3.3 mm (P < .001), and ICE measurement of native ASD diameters of 13.5 +/- 4.1 mm (P < .001). Single-plane ICE balloon sizing revealed diameters of 16.9 +/- 5.2 mm and corresponded well with fluoroscopy: R = 0.98, P < .001. CONCLUSION: As a sizing tool, ICE is an accurate alternative to fluoroscopy and helps to decrease radiation exposure.

Is there a relation between non-calcifying coronary plaques and acute coronary syndromes? A retrospective study using multislice computed tomography.

OBJECTIVES: The purpose of this study was to assess whether different coronary plaque types as classified by multislice computed tomography (CT) are retrospectively correlated with acute coronary syndromes (ACS) in an unselected study population. METHODS: Sixty-three consecutive patients were examined with 16-slice CT coronary angiography. Coronary plaque types were classified as calcifying type 1, mixed (calcifying > non-calcifying) type 2, mixed (non-calcifying > calcifying) type 3, and non-calcifying type 4. Patients who had an ACS within 17 days were included. All patients underwent invasive coronary angiography. RESULTS: Fifty-eight patients (92%) had coronary plaques evaluated by CT: 18 type 1 (31%), 10 type 2 (17%), 16 type 3 (28%) and 14 type 4 (24%). The presence of a non-calcifying plaque component (types 2-4; 40 of 63 patients, 63%) was correlated with ACS (n = 15; 24%) (p < 0.001). Only type 3 was significantly correlated with ACS (p = 0.01), but plaque types 2 and 4 were not. The diagnostic accuracy of CT for detection of stenosis >50% in proximal segments was: sensitivity 98%, specificity 90%, negative predictive value 97%, positive predictive value 97% per patient. CONCLUSIONS: Mixed calcifying/non-calcifying plaques with a predominantly non-calcifying component (type 3) as classified by multislice CT are retrospectively correlated with ACS.