Publications

First Dutch experience with percutaneous left atrial appendage transcatheter occlusion.

No abstract is provided for this article.

Characterization of alkali-activated thermally treated incinerator bottom ash

Survival and complaints after percutaneous aortic valve replacement

No abstract is provided for this article.

News Review: Lipid Technology 6/2007

Late stent malapposition occurring after intracoronary beta-irradiation detected by intravascular ultrasound.

We report a case of late stent malapposition occurring 6 months after intracoronary beta-irradiation detected by three-dimensional intravascular ultrasound, in spite of good apposition immediately after the procedure. Volumetric quantification revealed that stent volume remained unchanged, whereas total vessel volume increased by 13% after 6 months within the stent area. The increase of the vessel volume took place mainly in the proximal part of the stent, where the malapposition was located.

In vivo three dimensional optical coherence tomography. A novel imaging modality to visualize the edge vascular response

No abstract is provided for this article.

Edge detection versus videodensitometry for quantitative angiographic assessment of directional coronary atherectomy

The immediate efficacy of coronary atherectomy should be established by reproducible quantitative coronary analysis.1 The term “directional atherectomy” suggests that the device can be selectively directed toward the plaque and that its cutting mechanism is potentially less disruptive on vascular architecture than other angioplasty modalities. As a result of this selectively debulking action, the vessel may assume a more circular configuration, and cross-sectional area measurements obtained by edge detection and videodensitometry should become more comparable. This study was undertaken to determine whether videodensitometry and edge detection were equally acceptable methods in assessing the immediate results after atherectomy since the optimal method has not yet been established. Cineangiograms of 20 patients who underwent directional coronary atherectomy were analyzed with a computer-based coronary angiographic analysis system. The results of the cross-sectional area derived from contour analysis and videodensitometry were compared before and after directional atherectomy.

Does Cardiac Troponin I Overestimate Periprocedural Myocardial Infarction When Compared to Cardiac Troponin T?

No abstract is provided for this article.

New therapies for asthma: is there any progress?

Re-shuffling the Editorial Board

No abstract is provided for this article.

The effect of the novel phosphodiesterase-4 inhibitor MEM 1414 on the allergen induced responses in mild asthma

Inhaled allergen challenge is a standard method to study airway responses to inflammatory provocation and evaluate the therapeutic potential of novel anti-inflammatory compounds in asthma. MEM 1414 is a novel oral PDE4 inhibitor with high affinity and selectivity creating the potential for an improved side effect profile vs non-selective PDE inhibitors. We evaluated the tolerability and effect of MEM 1414 on airway responses in mild asthmatics. A randomised double blind placebo controlled cross over study in two centres, in which sixteen steroid naïve atopic asthmatics were challenged with inhaled allergen. Subjects were dosed with MEM 1414 (600 mg) or placebo, twice daily orally for 7 days. Allergen challenge was performed on day 6 (2 hours post-dose), and methacholine responsiveness was measured 24 hours post allergen (day 7). Biomarkers of drug effects using ex vivo LPS stimulation of whole blood production of interleukin (IL)-6 and leukotriene (LT)-B4 and fractional exhaled nitric oxide (FeNO) were measured on day 6 (0, 2 and 8 hours post-dose). Plasma pharmacokinetics were measured on days 1, 6 and 7. The primary endpoint was the effect on late asthmatic response to allergen. Treatment with MEM 1414 abrogated the late phase response with a mean difference in FEV1 (LAR 3–10 hours) of 104 ml (25%) vs placebo (p < 0.005), with no effect on the early response. Biomarker responses were also attenuated with MEM 1414 treatment with reductions in LPS-stimulated whole blood assays for TNFα at 8 hours (p < 0.03) and LTB4 at 24 hours (p = 0.0808) with no change in the IL-6 response. The MEM 1414 treatment phase was associated with higher incidence of nausea (6/16 MEM 1414 vs 2/16 placebo) and vomiting (3/16 vs 0/16 placebo). Oral MEM 1414, a novel PDE4 inhibitor, significantly reduces the late response following inhaled allergen challenge. MEM 1414 also inhibited whole blood assays of cytokine production from inflammatory cells. MEM 1414 was associated with a typical adverse event profile of PDE4 inhibitors, namely nausea and vomiting although these were mild side effects. Current controlled trials ISRCTN48047493 .

New-Onset Atrial Fibrillation After PCI or CABG for Left Main Disease

Background There is limited information on the incidence and prognostic impact of new-onset atrial fibrillation (NOAF) following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD). Objectives This study sought to determine the incidence of NOAF following PCI and CABG for LMCAD and its effect on 3-year cardiovascular outcomes. Methods In the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. Outcomes were analyzed according to the development of NOAF during the initial hospitalization following revascularization. Results Among 1,812 patients without atrial fibrillation on presentation, NOAF developed at a mean of 2.7 ± 2.5 days after revascularization in 162 patients (8.9%), including 161 of 893 (18.0%) CABG-treated patients and 1 of 919 (0.1%) PCI-treated patients (p < 0.0001). Older age, greater body mass index, and reduced left ventricular ejection fraction were independent predictors of NOAF in patients undergoing CABG. Patients with versus without NOAF had a significantly longer duration of hospitalization, were more likely to be discharged on anticoagulant therapy, and had an increased 30-day rate of Thrombolysis In Myocardial Infarction major or minor bleeding (14.2% vs. 5.5%; p < 0.0001). By multivariable analysis, NOAF after CABG was an independent predictor of 3-year stroke (6.6% vs. 2.4%; adjusted hazard ratio [HR]: 4.19; 95% confidence interval [CI]: 1.74 to 10.11; p = 0.001), death (11.4% vs. 4.3%; adjusted HR: 3.02; 95% CI: 1.60 to 5.70; p = 0.0006), and the primary composite endpoint of death, MI, or stroke (22.6% vs. 12.8%; adjusted HR: 2.13; 95% CI: 1.39 to 3.25; p = 0.0004). Conclusions In patients with LMCAD undergoing revascularization in the EXCEL trial, NOAF was common after CABG but extremely rare after PCI. The development of NOAF was strongly associated with subsequent death and stroke in CABG-treated patients. Further studies are warranted to determine whether prophylactic strategies to prevent or treat atrial fibrillation may improve prognosis in patients with LMCAD who are undergoing CABG. (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776)

The SYNTAX score on its way out or … towards artificial intelligence: part I

Preamble Recent publications on the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score have caught our attention and triggered a written reaction on the history and evolution of the SYNTAX score over the last decades. Among these publications, there is the editorial of Marie-Claude Morice, "Has the SYNTAX score become obsolete?"1. The most recent guidelines on revascularisation also question the ability of the SYNTAX II score to predict four-year all-cause mortality … even if the rate of mortality at four years in the EXCEL study was not yet available at the time ...

The effect of coronary bifurcation and haemodynamics in prediction of atherosclerotic plaque development: a serial computed tomographic coronary angiographic study

The aim of this study was to examine the effect of the daughter branches on the haemodynamics and the potential prediction of atherosclerotic plaque development as well as the best flow division model for accurate blood flow modelling.We analysed computed tomography coronary angiography retrospective data portraying 17 coronary artery bifurcations in 15 patients recruited into the PROSPECT MSCT study. Baseline and three-year follow-up imaging data were used to reconstruct coronary artery anatomy. In the baseline models blood flow simulations were performed using three flow division approaches: stress-free, Murray's law and Doriot's fit. Blood flow simulation was also performed omitting the daughter branch. The association between ESS estimated in models that incorporated the daughter branches and lumen reduction was higher than the cases where the side branch was omitted. Murray's law provides the most accurate results when comparing the different flow division models. More specifically, low ESS is a predictor of significant lumen reduction (p=0.007), plaque burden increase (p=0.0006) and necrotic core change (p=0.025).The ESS distribution in coronary models including the daughter branches and based on the calculations implementing Murray's law allows more accurate prediction of atherosclerotic evolution than ESS estimated in models including only the main vessel.

Greater Effect of Inhaled Budesonide on Adenosine 5′-Monophosphate-induced than on Sodium-Metabisulfite-induced Bronchoconstriction in Asthma

Inhaled glucocorticosteroids (GCS) decrease airway responsiveness (AR) in asthma by mechanisms that may involve suppressing airway inflammation and a reduction in the number of inflammatory cells in the airways. To investigate the functional response to a reduction in airway inflammatory cells in asthma, we studied the effects of inhaled budesonide on AR to three different bronchial challenges, adenosine 5′-monophosphate (AMP), which primarily activates mast cells; methacholine (MCh), a direct stimulus, and sodium metabisulfite (MBS), a neural stimulus. In a double-blind randomized crossover manner, with a washout period of 28 days, 12 subjects with mild asthma underwent inhalation challenge with doubling increments of MCh, MBS, and AMP before and after 14 days of treatment with budesonide 0.8 mg twice daily from a multidose dry-powder delivery system (Turbohaler) or matched placebo. Treatment with budesonide reduced AR to MCh and MBS to a similar degree, displacing the dose-response curve of each agonist to the right by 1.17 (95% confidence intervals, 0.34 to 2.00) and 1.06 (0.34 to 1.78) doubling dilutions, respectively, when compared with placebo (p < 0.01). Budesonide caused an additional and significantly greater reduction in AR to AMP, displacing the dose-response curve to the right by 2.92 (2.12 to 3.72) doubling dilutions when compared with placebo (p < 0.001) and to the other challenges (p < 0.01). We conclude that budesonide reduces AR to MCh and MBS by an action common to the effects of both direct and neural stimuli on airway smooth muscle contraction. The greater reduction in AR to AMP suggests that budesonide may have an additional action by reducing airway mast cell numbers and/or function.

Measurement of Granulocyte Pharmacodynamics in Whole Blood by Flow Cytometry

During the Phase I/II assessment of new therapies with the potential to suppress eosinophil and neutrophil inflammation, there is a need to assess the peripheral blood pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the drug. This has relevance in respiratory disease since drugs that target eosinophillic inflammation are in development for asthma; whereas neutrophil-directed therapies are being introduced for treatment of chronic obstructive airways disease (COPD). Pharmacokinetic evaluation is required to determine the concentration of drug substance (and possibly metabolites) in peripheral blood at intervals following single or repeated dosing. Pharmacodynamic assessment is also required since many drug substances have a duration of action which is prolonged beyond the time when drug substance is detectable in the blood (see Fig. 1). Fig. 1. Whole blood pharmacodynamics. In preclinical studies, animal or human blood is treated with test agents. In clinical studies, human subjects are treated with drug and blood removed for analysis. GAFS, gated autofluorescence forward scatter; PK, pharmacokinetics; PD, pharmacoldynamics.

In‐hospital complications after transcatheter aortic valve implantation revisited according to the valve academic research consortium definitions

Objectives: To determine the occurrence of in‐hospital complications after transcatheter aortic valve implantation (TAVI) according to the Valve Academic Research Consortium (VARC) criteria in addition to the length of stay (LOS). Background: The absence of uniformity in endpoint definitions challenges the comparison between previously reported major adverse cerebro‐ and cardiovascular event rates after TAVI. To address this, in 2009, the VARC was established aiming to provide standardized endpoint definitions for TAVI clinical trials. Methods: Between November 2005 and September 2010, we prospectively enrolled 150 consecutive patients who underwent TAVI with the Medtronic CoreValve System in our institution. Complications, prosthetic valve associated endpoints, and therapy‐specific endpoints were defined according to the definitions provided by the VARC. Results: The mean age (±SD) was 81 (±7) years and 55% were female. Thirty‐day or in‐hospital mortality was 11%, and the 30‐day combined safety endpoint was 22%. Seventy‐six patients (51%) had ≥1 cardiovascular and/or noncardiovascular complication of whom 16 also underwent a new permanent pacemaker implantation (PPI). In the 74 patients with uneventful TAVI, 12 patients (8%) underwent PPI. TAVI was truly uneventful in 62 patients (41%). Bleeding complications were observed most frequently (31%), followed by acute kidney injury (18%), vascular complications (16%), and stroke/TIA (11%). The median LOS in patients with a complicated and a truly uncomplicated TAVI was 14.0 (8.0–20.5) and 8.0 (7.0–10.8) days, respectively ( P &lt; 0.001). Conclusion: TAVI was associated with ≥1 cardiovascular and/or noncardiovascular event in 51% of the patients; new PPI was needed in another 8%, and TAVI was truly uncomplicated in 41%. Complications and need for new PPI significantly prolonged LOS. © 2011 Wiley‐Liss, Inc.

Cyclic nucleotides and phosphodiesterases and airway function

The cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) play an important role in the regulation of airway smooth muscle tone and activation of inflammatory cells. Intracellular concentrations of these nucleotides are tightly regulated by phosphodiesterases (PDEs). Several families of PDEs are now recognized and, within each isoenzyme family, molecular cloning has revealed multiple members. PDE III and IV are important in the breakdown of cAMP; PDE III is involved in the regulation of airway smooth muscle tone, whereas PDE IV is more important in inflammatory cells, including mast cells, macrophages, eosinophils, T-lymphocytes and epithelial cells. PDE V is involved in the breakdown of cGMP in airway and vascular smooth muscle. Regulation of PDE expression in health and disease is now under investigation. Several selective PDE inhibitors have recently been developed, and experimental studies indicate that PDE IV inhibitors may be useful as anti-inflammatory treatments in asthma. Clinical trials in asthma are now in progress.