Publications

The cyclic AMP phosphodiesterase (PDE) III/IV inhibitor, zardaverine, and the PDE IV-selective inhibitor, rolipram, both caused concentration-dependent inhibition of opsonized zymosan-stimulated superoxide anion generation by purified human peripheral blood eosinophils with approximate IC50 values of 30 and 40 microM, respectively. In contrast, the selective PDE III inhibitor, SK&F 94120, was ineffective in suppressing this functional response at concentrations below 100 microM. The inhibitory effects of rolipram and zardaverine on superoxide anion generation were increased in the presence of the beta-2 adrenoceptor agonist, albuterol, which itself was an inhibitor of eosinophil respiratory burst (IC50 = 20 microM). The effects of albuterol and the PDE inhibitors in combination were simply additive. Paradoxically, both rolipram and zardaverine significantly potentiated albuterol-induced cyclic AMP accumulation in a synergic fashion. Cyclic AMP PDE activity of eosinophil homogenates was inhibited by both zardaverine (IC50 = 515 nM) and rolipram (IC50 = 550 nM) as well as two other PDE IV-selective inhibitors, Ro 20-1724 (IC50 = 3.0 microM) and denbufylline (IC50 = 360 nM), whereas SK&F 94120 was ineffective. These data suggest that cyclic AMP levels in human eosinophils are regulated by the action of a type IV PDE isoenzyme and that elevation of the intracellular cyclic AMP concentration by PDE IV inhibition can suppress the functional activity of these cells. However, the suppressor effect of the PDE IV inhibitors appears to be independent of that of a beta-2 adrenoceptor agonist, implying a possible adenylyl cyclase-independent mechanism of action for beta agonists in eosinophils.

No abstract is provided for this article.

<h3>Objective</h3> Everolimus drug-eluting stents (EES) are superior to early-generation drug-eluting stents (DES), releasing sirolimus (SES) or paclitaxel (PES) in preventing stent thrombosis (ST). Since an impaired LVEF seems to increase the risk of ST, we aimed to investigate the difference in outcome of patients with varying LVEF using EES versus early-generation DES. <h3>Methods</h3> In a prospective cohort study, we compared the risk of ST in patients in three LVEF subgroups: normal (LVEF &gt;50%), mildly impaired (LVEF &gt;40% and ≤50%) and moderate–severely impaired (LVEF ≤40%). Within these various LVEF groups, we compared EES with SES and PES after adjustment for baseline differences. <h3>Results</h3> We assessed a cohort of 5363 patients, with follow-up of up to 4 years and available LVEF. Overall definite ST occurred in 123 (2.3%) patients. ST rates were higher in the LVEF moderate–severely impaired group compared with the normal LVEF group (2.8% vs 2.1%; HR 1.82; CI 1.10 to 3.00). Especially early ST (EST) was more frequent in the moderate–severely impaired LVEF group (HR 2.20; CI 1.06 to 4.53). Overall rates of definite ST were lower in patients using EES compared with patients using SES or PES in all LVEF groups. Interaction terms were not statistically significant. ST rates were higher in the moderate–severely impaired LVEF group compared with the normal LVEF group when using SES or PES, but not significantly different when using EES. <h3>Conclusions</h3> EES was associated with a lower risk of definite ST compared with early-generation DES. This lower risk was independent of LVEF, even though ST rates were higher in patients with a moderate–severely impaired LVEF. <h3>Trial registration no</h3> MEC-2013-262.

No abstract is provided for this article.

AIMS We evaluated a novel motion-compensating 3D reconstruction technique applied to rotational angiography (R-angio) which produces MSCT-like images for evaluation of implanted TAVI prostheses without requiring rapid pacing. METHODS AND RESULTS Fifty-one consecutive patients were retrospectively identified who were evaluated with rotational angiography (R-angio) using the Siemens Artis zee angiographic C-arm system after TAVI with a Medtronic CoreValve prosthesis. A novel 3D image reconstruction technique was applied which corrects for cardiac motion. CoreValve frame geometry was evaluated according to the same protocol for MSCT and R-angio at the level of: 1) the inflow, 2) the nadirs, 3) central coaptation, and 4) the commissures. The native aortic annulus dimensions were measured at the nadirs of the three leaflets. Sizing ratio, prosthesis expansion and frame ellipticity were assessed. Good quality 3D reconstructions were obtained in 43 patients (84%) and failure was predictable prior to reconstruction in six of the other seven patients (superposition of radiographically dense object n=4, obesity n=2). Prosthesis inflow ellipticity and expansion were correlated with implantation depth (respectively r=-0.46, p<0.01, and r=0.61, p<0.001). Aortic regurgitation grade ≥2 was associated with greater prosthesis ellipticity at the level of central coaptation (median [25th-75th percentile]: 1.15 [1.10-1.20] vs. 1.08 [1.06-1.12], p=0.009). The inter-observer, inter-modality (MSCT, R-angio) variability in measurement at the level of coaptation for minimum diameter, maximum diameter and area were all low (respectively, mean ±SD:1.2% ±1.2; 1.7% ±1.8 and 2.0% ±1.3). CONCLUSIONS R-angio with motion-compensated reconstruction offers new possibilities for evaluation of the post-implantation geometry of percutaneous structural heart prostheses and the potential clinical effects.

Background: Implantation of a metallic prosthesis creates local stiffness with a subsequent mismatch in the compliance of the vessel wall, disturbances in flow and heterogeneous distribution of wall shear stress. Polymeric bioresorbable ABSORB scaffolds have less stiffness than metallic platform stents. We sought to analyze the mismatch in vascular compliance after ABSORB implantation and its long-term resolution with bioresorption. Methods and Results: A total of 83 patients from the ABSORB trials underwent palpography investigations (30 and 53 patients from ABSORB Cohorts A and B, respectively) to measure the compliance of the scaffolded and adjacent segments at various time points (from pre-implantation up to 24 months). The mean of the maximum strain values was calculated per segment by utilizing the Rotterdam Classification (ROC) score and expressed as ROC/mm. Scaffold implantation lead to a significant decrease in vascular compliance (median [IQR]) at the scaffolded segment (from 0.37 [0.24-0.45] to 0.14 [0.09-0.23], P<0.001) with mismatch in compliance in a paired analysis between the scaffolded and adjacent segments (proximal: 0.23 [0.12-0.34], scaffold: 0.12 [0.07-0.19], distal: 0.15 [0.05-0.26], P=0.042). This reported compliance mismatch disappears at short- and mid-term follow-up. Conclusions: The ABSORB scaffold decreases vascular compliance at the site of scaffold implantation. A compliance mismatch is evident immediately post-implantation and in contrast to metallic stents disappears in the mid-term, likely leading to a normalization of the rheological behavior of the scaffolded segment. (Circ J 2012; 76: 1616–1623)

Objectives The study sought to investigate the impact of different computing methods for composite endpoints other than time-to-event (TTE) statistics in a large, multicenter registry of unprotected left main coronary artery (ULMCA) disease. Background TTE statistics for composite outcome measures used in ULMCA studies consider only the first event, and all the contributory outcomes are handled as if of equal importance. Methods The TTE, Andersen-Gill, win ratio (WR), competing risk, and weighted composite endpoint (WCE) computing methods were applied to ULMCA patients revascularized by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) at 14 international centers. Results At a median follow-up of 1,295 days (interquartile range: 928 to 1,713 days), all analyses showed no difference in combinations of death, myocardial infarction, and cerebrovascular accident between PCI and CABG. When target vessel revascularization was incorporated in the composite endpoint, the TTE (p = 0.03), Andersen-Gill (p = 0.04), WR (p = 0.025), and competing risk (p < 0.001) computing methods showed CABG to be significantly superior to PCI in the analysis of 1,204 propensity-matched patients, whereas incorporating the clinical relevance of the component endpoints using WCE resulted in marked attenuation of the treatment effect of CABG, with loss of significance for the difference between revascularization strategies (p = 0.10). Conclusions In a large study of ULMCA revascularization, incorporating the clinical relevance of the individual outcomes resulted in sensibly different findings as compared with the conventional TTE approach. In particular, using the WCE computing method, PCI and CABG were no longer significantly different with respect to the composite of death, myocardial infarction, cerebrovascular accident, or target vessel revascularization at a median of 3 years.

Sensory nerve activation will produce adherence of neutrophils to tracheobronchial microvessels. The aim of the present study was to investigate whether this adherence would lead to an influx of neutrophils into the airway lumen. To do this, we studied the effects of 20 minutes of vagal stimulation (1 Hz, 5 ms, 5 V) in anaesthetized and tracheostomized guinea-pigs on both lung resistance, and the cell picture in bronchoalveolar lavage. Any changes were compared to those of intravenous methacholine infusion, producing similar changes in lung resistance. Since high pressure ventilation could produce lung damage, we also studied the effects of ventilation through an extracorporeal resistor, producing a similar change in transpulmonary pressure (45 +/- 2 cmH2O) as vagal stimulation (42 +/- 4 cmH2O). The total number of cells recovered in the lavage was not increased by vagal stimulation, methacholine infusion or the extracorporeal resistor. However, both vagal stimulation and methacholine infusion significantly increased the relative number of neutrophils in the lavage compared to sham stimulated animals (21 +/- 11%, 13 +/- 4% and 4 +/- 1% respectively), but the extracorporeal resistor had no effect (4 +/- 2%). Our data suggests that prolonged bronchoconstriction per se may induce an influx of neutrophils into the airway lumen of the guinea-pig.

Aims:The Xeltis bioabsorbable pulmonary valved conduit (XPV), designed to guide functional restoration of patients' own tissue, is potentially more durable than current pulmonary bioprosthetic valves/valved conduits.The aim of this study was to assess the haemodynamic performance of the novel XPV implanted in an ovine model. Methods and results:The XPV was surgically implanted in adult sheep under general anaesthesia and cardiopulmonary bypass (XPV group, n=20).Sheep that received a Hancock bioprosthetic pulmonary valved conduit served as a control group (HPV group, n=3).Transthoracic echocardiograms from VARC-2 recommended time points at 3, 6, 9, 12, 18 and 24 months (XPV group) and at 3 and 6 months (HPV group) after the procedure were analysed in an independent core laboratory.The primary endpoint was favourable valved conduit performance, defined as peak systolic pressure gradient <40 mmHg, no severe pulmonary regurgitation (PR), and a maximum conduit patency index of -20%.In the latter, negative values denote luminal narrowing and vice versa.The valvular peak systolic pressure gradient (mmHg) was 25.6±9.7 (3 months), 19.6±7.1 (6 months), 10.0±9.2 (24 months) in the XPV group and 18.4±6.6(3 months), 17.7±4.6(6 months) in the HPV group.The patency index (%) of the conduit at the valvular level was +30.3±13.6 (6 months) and +64.1±1.4 (24 months) in the XPV group and +2.0±15.9(6 months) in the HPV group.PR was trace or mild at all visits, except in one animal with persistent moderate PR in the XPV group, up to 24 months. Conclusions:The XPV showed a favourable and durable haemodynamic performance (up to two years after implantation), without conduit narrowing/obstruction or severe regurgitation.

No abstract is provided for this article.

No abstract is provided for this article.