Publications

No abstract is provided for this article.

AimsPrimary percutaneous coronary intervention (PPCI) with thrombectomy (TB) seems to reduce the thrombus burden, resulting in a larger flow area as measured with optical frequency domain imaging (OFDI).

No abstract is provided for this article.

Whereas transthoracic echocardiography is the modality of choice for the diagnosis of severe aortic stenosis and cine-fluoroscopy is used to guide the implantation of the TAVI prosthesis, we believe that multislice computer tomography (MSCT) is the modality of choice for evaluation of the aortic root with a view to selecting patients with suitable anatomy and to guide sizing. We aim to describe an anatomical approach for the step by step interrogation of a 3D MSCT dataset to obtain the measurements of the aortic root required for patient selection, sizing and selection of the optimal angulation of the C-arm during the implantation procedure.The landmarks used to anatomically define the aortic annulus and structures of the aortic root may be used to define the same structures for measurement on a 3D MSCT dataset by setting up orthogonal cut-planes including one axial to the aortic annulus. This allows true axial diameter measurements and also enables us to define the valve plane.Measurement on the axial images avoids incorrect diameter measurements that do not pass through the central axis.

In chronic obstructive pulmonary disease (COPD), oxidative stress regulates the inflammatory response of bronchial epithelium and monocytes/macrophages through kinase modulation and has been linked to glucocorticoid unresponsiveness. Glycogen synthase-3β (GSK3β) inactivation plays a key role in mediating signaling processes upon reactive oxygen species (ROS) exposure. We hypothesized that GSK3β is involved in oxidative stress-induced glucocorticoid insensitivity in COPD. We studied levels of phospho-GSK3β-Ser9, a marker of GSK3β inactivation, in lung sections and cultured monocytes and bronchial epithelial cells of COPD patients, control smokers, and nonsmokers. We observed increased levels of phospho-GSK3β-Ser9 in monocytes, alveolar macrophages, and bronchial epithelial cells from COPD patients and control smokers compared with nonsmokers. Pharmacological inactivation of GSK3β did not affect CXCL8 or granulocyte-macrophage colony-stimulating factor (GM-CSF) expression but resulted in glucocorticoid insensitivity in vitro in both inflammatory and structural cells. Further mechanistic studies in monocyte and bronchial epithelial cell lines showed that GSK3β inactivation is a common effector of oxidative stress-induced activation of the MEK/ERK-1/2 and phosphatidylinositol 3-kinase/Akt signaling pathways leading to glucocorticoid unresponsiveness. In primary monocytes, the mechanism involved modulation of histone deacetylase 2 (HDAC2) activity in response to GSK3β inactivation. In conclusion, we demonstrate for the first time that ROS-induced glucocorticoid unresponsiveness in COPD is mediated through GSK3β, acting as a ROS-sensitive hub.

In the development of intravascular ultrasound (IVUS), a serious emphasis has been given to the improvement of the image quality in terms of resolution. The image quality is indeed a very important issue, but there is a lot more information hidden in the ultrasound signals than is currently exploited by commercially available IVUS equipment. For several years, at the Thorax Centre, we have been exploring the possibilities of analysing sequences of radiofrequency (RF) traces to extend the functionality of the IVUS machines. It gives possibilities for local elasticity assessment, flow estimation and enhanced lumen detection. This paper is an up to date report of where RF-data analysis has taken us.

Pressure-wire assessment of coronary stenosis is considered the invasive reference standard for detection of ischaemia-generating lesions. Recently, methods to estimate the fractional flow reserve (FFR) from conventional angiography without the use of a pressure wire have been developed, and were shown to have an excellent diagnostic accuracy. The present systematic review and meta-analysis aimed at determining the diagnostic performance of angiography-derived FFR for the diagnosis of haemodynamically significant coronary artery disease. A systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived FFR systems were performed. The primary outcome of interest was pooled sensitivity and specificity. Thirteen studies comprising 1842 vessels were included in the final analysis. A Bayesian bivariate meta-analysis yielded a pooled sensitivity of 89% (95% credible interval 83–94%), specificity of 90% (95% credible interval 88–92%), positive likelihood ratio (+LR) of 9.3 (95% credible interval 7.3–11.7) and negative likelihood ratio (−LR) of 0.13 (95% credible interval 0.07–0.2). The summary area under the receiver-operating curve was 0.84 (95% credible interval 0.66–0.94). Meta-regression analysis did not find differences between the methods for pressure-drop calculation (computational fluid dynamics vs. mathematical formula), type of analysis (on-line vs. off-line) or software packages. The accuracy of angiography-derived FFR was good to detect haemodynamically significant lesions with pressure-wire measured FFR as a reference. Computational approaches and software packages did not influence the diagnostic accuracy of angiography-derived FFR. A diagnostic strategy trial with angiography-derived FFR evaluating clinical endpoints is warranted.

Endogenous exhaled nitric oxide (NO) is increased during the late response to inhaled allergen in patients with asthma and may be bronchoprotective in asthma or have a deleterious effect when generated in excess under inflammatory conditions. To investigate this, we evaluated the effect of inhibiting endogenous NO production with nebulized N G-nitro-l-arginine methyl ester (l-NAME), a nonselective NO synthase (NOS) inhibitor, on early and late asthmatic responses to inhaled allergen in patients with mild allergic asthma. After a screening allergen challenge (AC), 22 male patients attended two visits conducted in a double-blind, randomized, placebo-controlled, crossover manner. Twelve patients demonstrating an early asthmatic response only (single responders) inhaled either l-NAME 170 mg or 0.9% saline 20 min before AC, with exhaled NO and FEV1 measured for 3 h. Ten patients demonstrating both early and late asthmatic responses (dual responders) were studied in a similar fashion but inhaled two further doses of l-NAME or placebo 3.5 and 7 h after the initial dose, with exhaled NO and FEV1 measured for 10 h. l-NAME reduced exhaled NO levels by 77 ± 5% (p < 0.01) and 71 ± 7% (p < 0.01) in single and dual responders, respectively, but had no significant effect on early or late asthmatic responses. Following AC in single responders, the mean ( ± SEM) maximum fall in FEV1 after l-NAME and saline was 21.2 ± 2.9% and 23.8 ± 3.0%, respectively, and in dual responders, 31.2 ± 4.5% and 31.8 ± 5.8% during the early asthmatic responses, and 27.4 ± 3.9% and 30.6 ± 4.5% during the late asthmatic responses, respectively. Area under the curve (AUC) did not significantly differ. AUC0–2 h in single responders after l-NAME and saline was 20.2 ± 3.9 and 24.9 ± 4.4 Δ % FEV1/h, and in dual responders, 37.6 ± 8.4 and 36.7 ± 8.4 Δ % FEV1/h, respectively, and 106.2 ± 18.9 and 117.1 ± 22.4 Δ % FEV1/h, respectively, for the AUC4–10 h. This study suggests that in mild allergic asthma, endogenous NO neither protects against nor contributes to the processes underlying airway responses to inhaled allergen.

Bioresorbable scaffolds offer the possibility of transient scaffolding of the vessel to prevent acute vessel closure and recoil while also transiently eluting an antiproliferative drug to counteract the constrictive remodeling and excessive neointimal hyperplasia. The concept of a transient coronary device that disappears after doing its job fits the physiological demand to restore the vessel structure and seems attractive both to physicians and patients. Following the successful and intriguing findings observed in the first-in-human trials, the four products, Absorb, Desolve, ART, and Magmaris scaffolds succeeded to acquire a CE mark.

The safety and performance of the Absorb Bioresorbable Vascular Scaffold (Absorb BVS) system (Abbott Vascular, Santa Clara, CA, USA) has been previously established in 131 patients from cohort A and cohort B of the first-in-man ABSORB trial. Following this trial, ABSORB EXTEND was initiated as a global continued access study (outside of the USA) to expand experience with the Absorb BVS system to different geographies with broader inclusion criteria to include the treatment of longer lesions and multiple vessels. We report in this manuscript the twelve-month clinical outcomes of the first 512 patients in this population.ABSORB EXTEND is a prospective, single-arm, open-label clinical study which will enrol up to 800 patients at up to 100 sites. Included are patients with lesions ≤28 mm in length and reference vessel diameter of 2.0-3.8 mm (as assessed by on-line QCA or IVUS). Treatment of a maximum of two de novo native coronary artery lesions is permitted when each lesion is located in a different epicardial vessel. An independent clinical events committee adjudicates all endpoint-related events. At one year, for the first 512 patients enrolled in the study, the composite endpoints of ischaemia-driven MACE and ischaemia-driven target vessel failure were 4.3% and 4.9%, respectively. The cumulative rate of ARC defined definite and probable scaffold thrombosis for this population was 0.8% at one year.This interim analysis of the ABSORB EXTEND study shows low rates of MACE and scaffold thrombosis. The study is registered on clinicaltrials.gov (unique identifier NCT01023789).