Publications

Incidence of High-Strain Patterns in Human Coronary Arteries

Rupture of thin-cap fibroatheromatous plaques is a major cause of acute myocardial infarction (AMI). Such plaques can be identified in vitro by 3D intravascular palpography with high sensitivity and specificity. We used this technique in patients undergoing percutaneous intervention to assess the incidence of mechanically deformable regions. We further explored the relation of such regions to clinical presentation and to C-reactive protein levels.Three-dimensional palpograms were derived from continuous intravascular ultrasound pullbacks. Patients (n=55) were classified by clinical presentation as having stable angina, unstable angina, or AMI. In every patient, 1 coronary artery was scanned (culprit vessel in stable and unstable angina, nonculprit vessel in AMI), and the number of deformable plaques assessed. Stable angina patients had significantly fewer deformable plaques per vessel (0.6+/-0.6) than did unstable angina patients (P=0.0019) (1.6+/-0.7) or AMI patients (P<0.0001) (2.0+/-0.7). Levels of C-reactive protein were positively correlated with the number of mechanically deformable plaques (R2=0.65, P<0.0001).Three-dimensional intravascular palpography detects strain patterns in human coronary arteries that represent the level of deformation in plaques. The number of highly deformable plaques is correlated with both clinical presentation and levels of C-reactive protein. Further studies will assess the potential role of the technique to identify patients at risk of future clinical events

Extremely low cycle fatigue tests on structural carbon steel and stainless steel

The continuous strength method for the design of aluminium alloy structural elements

P6405Implications of the local haemodynamic forces on plaque morphology: A serial intravascular ultrasound and optical coherence tomography analysis

No abstract is provided for this article.

Impact of Body Mass Index on the Five-Year Outcome of Patients Having Percutaneous Coronary Interventions With Drug-Eluting Stents

The purpose of this study was to assess the impact of body mass index (BMI) on clinical outcome of patients treated by percutaneous coronary intervention (PCI) using drug-eluting stents. Patients were stratified according to BMI as normal (<25 kg/m2), overweight (25 to 30 kg/m2), or obese (>30 kg/m2). At 5-year follow-up all-cause death, myocardial infarction, clinically justified target vessel revascularization (TVR), and definite stent thrombosis were assessed. A complete dataset was available in 7,427 patients, of which 45%, 22%, and 33% were classified according to BMI as overweight, obese, and normal, respectively. Mean age of patients was significantly older in those with a normal BMI (p <0.05). Incidence of diabetes mellitus, hypertension, and dyslipidemia increased as BMI increased (p <0.05). Significantly higher rates of TVR (15.3% vs 12.8%, p = 0.02) and early stent thrombosis (1.5% vs 0.9%, p = 0.04) were observed in the obese compared to the normal BMI group. No significant difference among the 3 BMI groups was observed for the composite of death/myocardial infarction/TVR or for definite stent thrombosis at 5 years, whereas the normal BMI group was at higher risk for all-cause death at 5 years (obese vs normal BMI, hazard ratio 0.74, confidence interval 0.53 to 0.99, p = 0.05; overweight vs normal BMI, hazard ratio 0.73, confidence interval 0.59 to 0.94, p = 0.01) in the multivariate Cox proportional hazard model. Age resulted in a linearly dependent covariate with BMI in the all-cause 5-year mortality multivariate model (p = 0.001). In conclusion, the “obesity paradox” observed in 5-year all-cause mortality could be explained by the higher rate of elderly patients in the normal BMI group and the existence of colinearity between BMI and age. However, obese patients had a higher rate of TVR and early stent thrombosis and a higher rate of other risk factors such as diabetes mellitus, hypertension, and hypercholesterolemia.

Prognostic Determinants of Coronary Atherosclerosis in Stable Ischemic Heart Disease

Risk stratification in patients with stable ischemic heart disease is essential to guide treatment decisions. In this regard, whether coronary anatomy, physiology, or plaque morphology is the best determinant of prognosis (and driver an effective therapeutic risk reduction) remains one of the greatest ongoing debates in cardiology. In the present report, we review the evidence for each of these characteristics and explore potential algorithms that may enable a practical diagnostic and therapeutic strategy for the management of patients with stable ischemic heart disease.

CRosser As First choice for crossing Totally occluded coronary arteries (CRAFT Registry): focus on conventional angiography and computed tomography angiography predictors of success

We investigated the use of the CROSSER catheter, a CTO crossing device based upon high frequency mechanical vibration, as a first resort to treat patients with chronic total occlusions (CTO) while describing angiographic and computed tomography coronary angiography (CTCA) serving as predictors for success.Eighty consecutive patients were enrolled in this prospective multicentre registry of patients treated for a CTO. For 76.3% of the patients, this was the first attempt to open the CTO. Overall success rate was 75%. By conventional coronary angiography, the length of the occlusion was 26.7±14.1 mm and there was a difference in successful vs. unsuccessful cases (24.5±13.9 and 32.8±13.1, p=0.02). The presence of angulation, as defined qualitatively, was more prevalent in failed cases (60.0% vs. 32.2%, p=0.03). The mean ratio CROSSER distance within the occlusion site and length of the occlusion showed a trend towards statistical significance in successful procedures (0.56±0.90 vs. 0.30±0.34, p=0.08). During hospitalisation, two patients had a non-fatal myocardial infarction. One patient experienced delayed onset of tamponade six hours postprocedure. At 30 days, two patients had PCI in a non-treated vessel and one patient had a transient ischaemic attack. Relation to the CROSSER catheter was inconclusive.The success rate of the use of a dedicated-CTO device--the CROSSER catheter--as a first choice to open a chronic total occlusion was 75%. By multivariate analysis, in a subset of patients that were imaged with computed tomography coronary angiography, the absence of angulation was related with higher success rate.

Reference Information

TCT-765 Lipid-Lowering Therapy in Contemporary PCI Practice

No abstract is provided for this article.

Effects of Percutaneous Transluminal Septal Myocardial Ablation for Obstructive Hypertrophic Cardiomyopathy on Systolic and Diastolic Left Ventricular Function Assessed by Pressure–Volume Loops

The aim of the present study was to determine the long-term effects of percutaneous transluminal septal myocardial ablation (PTSMA) on systolic and diastolic left ventricular (LV) functions in patients with obstructive hypertrophic cardiomyopathy (HC). Ten consecutive patients with symptomatic HC despite optimal medical treatment were referred for PTSMA at our center. LV systolic and diastolic functions were assessed by online LV pressure–volume loops obtained by conductance catheter at baseline and at 6 months after the procedure. At follow-up, the mean gradients at rest and after extrasystole were significantly decreased compared with baseline (88 ± 29 to 21 ± 11 mm Hg and 130 ± 50 to 35 ± 22 mm Hg, respectively, p <0.01 for the 2 comparisons). End-systolic and end-diastolic pressures significantly decreased (p <0.01), whereas end-systolic and end-diastolic LV volumes significantly increased (p <0.01 for the 2 comparisons). Cardiac output and stroke volume were unchanged, as were ejection fraction (p = 0.25) and maximum dP/dt (p = 0.13). The slope of the end-systolic pressure–volume relation was not decreased, indicating a preserved contractility. The relaxation constant time, end-diastolic stiffness, projected volume of the end-diastolic pressure–volume relation at 30 mm Hg, and diastolic stiffness constant showed a significant improvement of active and passive myocardial diastolic properties. In conclusion, PTSMA is an effective method in the treatment of symptomatic patients with HC. At 6-month follow-up, the LV–aortic gradient was decreased and active and passive LV diastolic properties were increased. Myocardial contractility was not decreased and general hemodynamics was maintained.

Activated protein phosphatase PP2A by formoterol enhances nuclear translocation of glucocorticoid receptor induced by budesonide

Introduction: We have reported that formoterol (FM), a long-acting β2- adrenoceptor agonist, restores corticosteroid (CS) sensitivity by activation of a serine/threonine protein phosphatase PP2A (ERJ 2009;34:583s). However, the molecular mechanisms how FM activates PP2A and restores CS sensitivity have not been elucidated. Aims: To investigate the mechanism of PP2A activation by FM and the involvement of PP2A in glucocorticoid receptor (GR) nuclear translocation induced by CS budesonide (BUD). Methods: Phosphatase activity of immunopurified PP2A from U937 monocytic cells was measured by fluorescence-based assay. A549 lung epithelial cells, without functional β2-adrenoceptor, were used as control cells. Direct effect of FM was evaluated using PP2A immunopurified from cell membrane and recombinant PP2A. Nuclear/cytoplasmic GR ratios under PP2A inhibition by okadaic acid (OA) or overexpression were determined by western-blot. Results: FM enhanced PP2A activity in both U937 and A549 cells and the effects were not blocked by a β2-adrenoceptor inhibitor (ICI-118551). FM directly activated PP2A-immunoprecipitates in the membrane and recombinant PP2A. PP2A was detected in GR-immunoprecipitates. PP2A inactivation by OA reduced GR nuclear translocation by BUD and abrogated FM-mediated increase of GR translocation while PP2A overexpression enhanced BUD-induced GR translocation and further increased enhancement of GR translocation by FM. Conclusions: FM directly activates PP2A in a β2-adrenoceptor-independent manner. PP2A associated with GR enhances GR nuclear translocation by BUD. This mechanism may contribute to the clinical benefits of BUD+FM combination therapy.

Coronary stenting with polymer-coated and uncoated self-expanding endoprostheses in pigs

Background: Preliminary clinical reports suggest that metallic stents are thrombogenic during the first days to weeks after implantation but that restenosis rates after this period may be reduced. Methods: We investigated the angiographic patency and histologically measured neointimal hyperplasia of 48 uncoated self-expanding, stainless steel mesh stents (Wallstent, Schneider [Europe] AG, Bulach, Switzerland) placed in normal coronary arteries of three groups of eight pigs that received postprocedure aspirin (ASA, group B), acenocoumarol (group C), or no medication (group A). The results were compared with those obtained in a fourth group of eight pigs (group D) receiving 15 polymer-coated (BioGold, PlasmaCarb Inc., Bedford, NH, USA) Wallstent stents, which are designed to reduce thrombogenicity without additional medication. After 1, 4, and 12 weeks, angiography was repeated. After the last angiogram the coronary arteries were pressure-fixated followed by light microscopy, immunocytochemistry, and electron microscopic examination. Results: Group A showed a 38% thrombotic occlusion rate within 1 week, which was prevented by acenocoumarol or polymer coating, but not by ASA. Histologic analysis showed no difference in the thickness of neointimal hyperplasia between the groups (median values: 134, 101, 143 and 113 μm for groups A, B, C, and D, respectively). Polymer coating did not induce an inflammatory reaction. Conclusions: Acenocoumarol and the polymer coating protected against early thrombotic occlusion of stainless steel self-expanding stents, but neointimal hyperplasia was not affected by preventive measures against stent thrombosis.

Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome

Abstract Background: Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking. Objective: To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease. Methods: In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values &lt; 0.05 were considered statistically significant. Results: In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm2 (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23). Conclusion: In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

Cyclic testing and numerical modelling of carbon steel and stainless steel tubular bracing members

Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma

About 5-10% of patients with asthma suffer from poorly controlled disease despite corticosteroid (CS) treatment, which may indicate the presence of CS insensitivity. A study was undertaken to determine whether relative CS insensitivity is present in alveolar macrophages from patients with severe asthma and its association with p38 mitogen-activated protein kinase (MAPK) activation and MAPK phosphatase-1 (MKP-1).Fibreoptic bronchoscopy and bronchoalveolar lavage (BAL) were performed in 20 patients with severe asthma and 19 with non-severe asthma and, for comparison, in 14 normal volunteers. Alveolar macrophages were exposed to lipopolysaccharide (LPS, 10 mug/ml) and dexamethasone (10(-8) and 10(-6) M). Supernatants were assayed for cytokines using an ELISA-based method. p38 MAPK activity and MKP-1 messenger RNA expression were assayed in cell extracts.The inhibition of LPS-induced interleukin (IL)1beta, IL6, IL8, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha release by dexamethasone (10(-6) M) was significantly less in macrophages from patients with severe asthma than in macrophages from patients with non-severe asthma. There was increased p38 MAPK activation in macrophages from patients with severe asthma. MKP-1 expression induced by dexamethasone and LPS, expressed as a ratio of LPS-induced expression, was reduced in severe asthma.Alveolar macrophages from patients with severe asthma demonstrate CS insensitivity associated with increased p38 MAPK activation that may result from impaired inducibility of MKP-1.

Sirolimus-eluting stents for the treatment of atherosclerotic ostial lesions.

Ostial atherosclerotic lesions are distinct from other lesion sites in terms of outcomes following percutaneous interventions. Despite aggressive lesion modification strategies, long-term outcome is hampered by restenosis. Various stent designs have failed to show significant improvement in target lesion revascularization (TLR) rates. The present study evaluates the clinical outcomes following sirolimus-eluting stent implantation for ostial lesions.The sirolimus-eluting stent (SES) was the device of choice at our institute for all coronary interventions from April 2002 to March 2003. This study population is comprised of 50 patients who received drug-eluting stents for atherosclerotic ostial lesions during this period. Sixty-eight percent of the patients were male and 24 patients (48%) had a history of previous revascularization. Indication for intervention were as follows: acute myocardial infarction, 7 patients (14%), stable angina, 23 patients (46%), unstable angina, 20 patients (40%). Angioplasty and stent implantations were done according to the standard protocol. All patients were prospectively followed up for major adverse cardiac events. The event-free survival was 90% at one year. There were 5 (10%) target vessel revascularization, 3 (6%) myocardial infarctions and 1 (2%) death during a mean follow-up of 414.5 +/- 54.5 days. TLR was required in 4 (8%) patients.SES implantation is feasible in ostial locations and is associated with low subsequent revascularization.

Relation of genetic profile and novel circulating biomarkers with coronary plaque phenotype as determined by intravascular ultrasound: rationale and design of the ATHEROREMO-IVUS study

The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis - Intravascular Ultrasound (ATHEROREMO-IVUS) study aims to investigate the relations of genetic profile and novel circulating biomarkers with coronary plaque phenotype and vulnerability as determined by intravascular ultrasound (IVUS).ATHEROREMO-IVUS is a prospective, observational cohort study of 846 patients with stable angina pectoris or acute coronary syndrome (ACS) who are referred for coronary angiography. Prior to the catheterisation procedure, blood samples are drawn for biomarker measurements and genetic analyses. During the catheterisation procedure, IVUS is performed in a non-culprit coronary artery. The primary endpoint is the presence of vulnerable plaque as determined by IVUS virtual histology. Secondary endpoints include the incidence of major adverse cardiac events during long-term follow-up.Results from ATHEROREMO-IVUS are expected to improve our knowledge of the role of genetic profile and circulating biomarkers in relation to the development of atherosclerosis and vulnerable plaques. Assessment and early validation of the prognostic value of novel biomarkers and intracoronary imaging techniques will be performed. (ClinicalTrials.gov number: NCT01789411).

Coronary and systemic hemodynamic effects of intravenous nisoldipine

Systemic and coronary hemodynamic effects of the new dihydropyridine calcium antagonist nisoldipine were studied over a 30-minute period in 12 patients with angina pectoris. Previously instituted β-blocker therapy was continued. Nisoldipine was administered in an intravenous bolus of 6 μg/kg over 3 minutes. Heart rate increased as mean aortic pressure and systemic vascular resistance decreased in all patients. Cardiac output increased significantly, from 5.8 ± 0.3 to 7.9 ± 0.5 liters/min, 10 minutes after nisoldipine infusion. These trends were maintained over the 30-minute observation period. Coronary sinus blood flow increased from 103 ± 11 to 139 ± 13 ml/min immediately after nisoldipine, but had returned to the control level by 30 minutes, as had the reduction in coronary vascular resistance. Myocardial oxygen consumption and heart rate-systolic blood pressure product did not change significantly. Nisoldipine is a potent peripheral and coronary vasodilator free of major myocardial depressant effects after acute intravenous administration. The systemic vasodilatory effects appear to outlast the coronary effects over 30 minutes.