Publications

The aim of this study was to compare the strut coverage of the XIENCE stent with that of the BuMA Supreme sirolimus-eluting cobalt-chromium stent, which has a shorter drug elution, on optical coherence tomography (OCT) one or two months after implantation.The PIONEER-II OCT trial was a multicentre, two-arm randomised trial, which comprised two cohorts: cohort-1 underwent an OCT imaging one month after coronary intervention (BuMA: 16 patients with 18 lesions, XIENCE: 15 patients with 17 lesions), whereas cohort-2 underwent OCT at two months (BuMA: 21 patients with 21 lesions, XIENCE: 23 patients with 28 lesions). The primary hypotheses were non-inferiority of the BuMA stent to the XIENCE stent in percent strut coverage at one month (cohort-1) or two months (cohort-2). In cohort-1, the BuMA stent was non-inferior to the XIENCE stent in terms of the strut coverage (83.8±10.4% for BuMA vs. 73.0±17.5% for XIENCE, pfor noninferiority <0.001), and was also significantly higher than the XIENCE (pfor superiority 0.037). In cohort-2, the BuMA stent was non-inferior to the XIENCE stent in OCT strut coverage (80.3±18.3% vs. 73.3±21.3%, pfor noninferiority 0.006, pfor superiority 0.24). Healing scores showed better healing in the BuMA stent in cohort-1 (32.36±21.59 vs. 54.88±34.65, p=0.027), whereas there was comparable healing between the BuMA and XIENCE stents in cohort-2 (39.86±37.77 vs. 53.75±42.84, p=0.25).The BuMA Supreme had a faster coverage than the XIENCE at one month, presumably due to faster and shorter sirolimus elution. The difference in tissue coverage became less evident at two months.

The assessment of coronary flow reserve from the instantaneous distribution of the contrast agent within the coronary vessels and myocardial muscle at the control state and at maximal flow has been limited by the superposition of myocardial regions of interest in the two-dimensional images. To overcome these limitations, we are in the process of developing a three-dimensional (3D) reconstruction technique to compute the contrast distribution in cross sections of the myocardial muscle from two orthogonal cineangiograms. To limit the number of feasible solutions in the 3D- reconstruction space, the 3D-geometry of the endo- and epicardial boundaries of the myocardium must be determined. For the geometric reconstruction of the epicar-dium, the centerlines of the left coronary arterial tree are manually or automatically traced in the biplane views. Next, the bifurcations are detected automatically and matched in these two views, allowing a 3D-representation of the coronary tree. Finally, the circumference of the left ventricular myocardium in a selected cross section can be computed from the intersection points of this cross section with the 3D coronary tree using B-splines. For the geometric reconstruction of the left ventricular cavity, we envision to apply the elliptical approximation technique using the LV boundaries defined in the two orthogonal views, or by applying more complex 3D-reconstruction techniques including densitometry. The actual 3D-reconstruction of the contrast distribution in the myocardium is based on a linear programming technique (Transportation model) using cost coefficient matrices. Such a cost coefficient matrix must contain a maximum amount of a priori information, provided by a computer generated model and updated with actual data from the angiographic views. We have only begun to solve this complex problem. However, based on our first experimental results we expect that the linear programming approach with advanced cost coefficient matrices and computed model will lead to acceptable solutions in the 3D-reconstruction of the myocardial contrast distribution from biplane cineangiograms.

Background Computerized quantitative coronary angiography (QCA) has fundamentally altered our approach to the assessment of coronary interventional techniques and strategies aimed at the prevention of recurrence and progression of stenosis. It is essential, therefore, that the performance of QCA systems, upon which much of our scientific understanding has become integrally dependent, is evaluated in an objective and uniform manner. Methods and Results We validated 10 QCA systems at core laboratories in North America and Europe. Cine films were made of phantom stenoses of known diameter (0.5 to 1.9 mm) under four experimental conditions: in vivo (coronary arteries of pigs) calibrated at the isocenter or by use of the catheter as a scaling device and in vitro with 50% contrast and 100% contrast. The cine films were analyzed by each automated QCA system without observer interaction. Accuracy and precision were taken as the mean and SD of the signed differences between the phantom stenoses, and the measured minimal luminal diameters and the correlation coefficient ( r ), the SEE, the y intercept, and the slope were derived by their linear regression. Performance of the 10 QCA systems ranged widely: accuracy, +0.07 to +0.31 mm; precision, ±0.14 to ±0.24 mm; correlation ( r ), .96 to .89; SEE, ±0.11 to ±0.16 mm; intercept, +0.08 to +0.31 mm; and slope, 0.86 to 0.64. Conclusions There is a marked variability in performance between systems when assessed over the range of 0.5 to 1.9 mm. The range of accuracy, intercept, and slope values of this report indicates that absolute measurements of luminal diameter from different multicenter angiographic trials may not be directly comparable and additionally suggests that such absolute measurements may not be directly applicable to clinical practice using an on-line QCA system with a different edge detection algorithm. Power calculations and study design of angiographic trials should be adjusted for the precision of the QCA system used to avoid the risk of failing to detect small differences in patient populations. This study may guide the fine-tuning of algorithms incorporated within each system and facilitate the maintenance of high standards of QCA for scientific studies.

Introduction Visual estimation of vessel diameter and lesion length supported by balloon predilation (known length and diameter) has been a common strategy, when final stent implantation is anticipated. Quantitative coronary angiography (QCA) being highly accurate and reproducible can refine the visual estimate and provide several important parameters which have been accepted as surrogate endpoints in many clinical studies on new PCI technologies. However, stand-alone percent diameter/area stenosis measurements derived from conventional (single-vessel) twodimensional (2-D) QCA analysis fail to predict the functional significance of coronary vessel obstruction. This holds even more for the analysis of bifurcation lesions, where the discrepancy in vessel size proximal and distal to the carina (step-down phenomenon) results in stenosis being overestimated in the distal branches and underestimated in the proximal main vessel (PMV). Dedicated 2-D bifurcation software algorithms have been developed recently in order to make up for the shortcomings of 2-D singlevessel QCA by reporting angiographic parameters separately for the PMV and each of the distal branches. The proximal and the distal branches of a single bifurcation often do not lie on a single plane; thus vessel overlap and foreshortening together with the lesion eccentricity may compromise the results of 2-D angiographic analysis. In the last 10 years evidence has accumulated that three dimensional (3-D) angiographic reconstruction is accurate, precise and reproducible. Reduced time requirements for a single 3-D reconstruction facilitates realtime analysis; single-vessel as well as bifurcation lesions can be reconstructed and analysed via dedicated QCA algorithms. In this short review we will attempt to emphasise the relative merits of bifurcation QCA compared to visual assessment, report on the options currently available for 2-D and 3-D bifurcation QCA analysis and outline the challenges yet to be addressed.

<b>Introduction:</b> Exposure to biomass smoke (BMS) particles in developing countries is a major cause COPD. BMS particles are phagocytosed by lung macrophages which elicit an inflammatory response. It is not yet understood which pathways are involved in this process. <b>Methods:</b> BMS particles were collected from an Indian cookstove burning wood and animal dung. Monocyte-derived macrophages (MDM) were isolated from non-smokers and COPD subjects and differentiated for 12 days in GM-CSF (G-φ) or M-CSF (M-φ) prior exposure to 30μg/ml BMS +/- Polymixin (10μg/ml). MDM were lysed and western blots for phosphorylated and total IKB-α, P-38 and ERK were performed. <b>Results:</b> Exposure of both G-φ and M-φ to BMS increased phosphorylation of IKB-α, P-38 and ERK at 30 and 60 min. M-φ from both NS and COPD subjects were more responsive to BMS compared to G-φ (Table 1). In all cases, phosphorylation could be suppressed by ~50% by inclusion of the LPS chelator, polymyxin B. Table.1: Densitometry of Phosphorylated/Total protein following 60min exposure of MDM to BMS. *p=0.05, **p=0.01 for differences between G-φ and M-φ <b>Conclusion:</b> BMS activates macrophage IKB-α, P-38 and ERK pathways that may lead to increased inflammatory responses of these cells. Half the signal can be attributed to LPS contamination, however the particles still drive an LPS independent response. These data suggest that IKBα and MAP kinase inhibitors may reduce macrophage responses to BMS particles and potentially progression of COPD.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however. Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from non-smokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays. MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR. MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD.

Drug-eluting stents (DES) are still the standard of care in percutaneous coronary intervention (PCI) since the fall of bioresorbable scaffolds with respect to safety. The unbeatable advantage of a metallic stent when compared with a scaffold is a stronger mechanical property and more sustainable vascular support. Recent development of contemporary metallic stent has focused on the reduction of strut thickness. However, there will always be a trade-off between improvement in deliverability, flexibility, and radial strength.This review aims to discuss the designs of metallic stent platform and mechanical properties as well as mechanical performance of contemporary DES from bench studies and clinical trials.Mechanical properties of stents affect short- and long-term clinical outcomes. Ultrathin-strut DES have become popular and clinical trials have shown impressive results. Thinner struts may improve device flexibility and deliverability but the radial strength and longitudinal integrity might have been compromised as well. Ultrathin-strut cobalt chromium or platinum chromium DES will become standard of care in PCI practice in the near future. Information on the stent design, stent material and mechanical properties of the stent are essential for a rational selection of the appropriate stent in selected lesions and patients.

Introduction: Peripheral and central airways nitric oxide (NO) can be partitioned using the multiple constant exhalation flows (Tsoukias et al 1998). We hypothesized that the choice of different flows and breath-hold periods may affect the results. Objective: To investigate the effect of different combinations of multiple exhalation flow rates and breath hold on the bronchial production (JawNO) and alveolar concentration of NO(CANO) in healthy subjects. Methods: Fractional exhaled NO (FeNO) was measured (Niox Flex, Aerocrine, Sweden) in 18 healthy subjects (34.5± 6.52 years), using different sets of flows: Set1: 10,30,50,100,200,300 ml/sec; Set2: 30,50,100,200,300ml/sec; Set3: 50,100,200,300ml/sec; Set4: 100,200,300ml/sec; Set5:50,100,200ml/sec; Set6: 30,50,100,200ml/sec; Set7:10,50,100,200ml/sec; Set8: 10,30,50,100,200ml/sec. In addition, in a separate experiment, eExhaled NO was measured after a 20 seconds breath-hold at total lung capacity. Results: JawNO and CANO were significantly affected by different sets of flow rates and varied between 632.5± 70.58 pl/sec and 892.0±109.4 pl/sec (p Conclusion: The choice of different sets of exhalation flow rates significantly affect JawNO and CANO, therefore, standardization of the measurements is required. In addition, breath holding should be avoided as it significantly affects NO parameters. We acknowledge the support of the ERS, Fellowship STRTF 373-2011.