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The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown.

I n Part I of this article, the definitions, prevalence, and clinical presentation of chronic total occlusions (CTOs) were reviewed, the histopathology of CTOs was examined, efforts to replicate human CTOs with experimental models were appraised, and the clinical relevance and rationale for CTO revascularization were evaluated. 1In Part II, we summarize the technical approach to and outcomes after percutaneous coronary intervention (PCI) of occluded coronary arteries, describe the novel devices and drugs approved and undergoing investigation for CTO recanalization, and conclude with practical perspectives on managing the patient with 1 or more chronic coronary occlusions.

No abstract is provided for this article.

OBJECTIVE: To assess the safety and efficacy of the implantation of Paclitaxel Eluting Stents (PES) for de novo, non‐flow limiting lesions. METHODS AND RESULTS: We assessed the 12‐month occurrence of major adverse cardiac events (MACE) in 21 patients (4% of the total population treated in a 'real world' registry) with 22 non‐significant coronary narrowings treated with PES. The following criteria had to be met: (1) the lesion was de novo; (2) the location was non‐ostial, and not a bifurcation lesion; (3) the diameter stenosis by quantitative coronary angiography (QCA) was <50%; (4) there was no visible thrombus and (5) the lesion was not located in an angiographically diffusely diseased segment. Procedural success rate was 100% without any periprocedural myocardial infarction. After a mean follow‐up of 407.33±53 (range: 344–498) days the overall MACE‐free survival was 95.2%. Freedom from target revascularization was 95.2%. CONCLUSIONS: The result of this non‐randomized observational study suggests that the implantation of PES for de novo, non‐significant lesions appears most probably safe and effective.

No abstract is provided for this article.

Background and aim Local hemodynamic changes are one of the main factors that determine the vessel wall biological response after stent/scaffold implantation. Computational fluid dynamic studies provide an opportunity to investigate the rheological effects of implanted stent/scaffold. The aim of this study was to assess the local hemodynamic microenvironment in scaffolded segments in porcine coronary models. Methods In six epicardial coronary arteries of healthy mini-pigs, six Absorb bioresorbable vascular scaffolds (Absorb BVS) were implanted. Optical coherence tomography(OCT) was performed after scaffold implantation and the images were fused with the angiographic data to reconstruct the three-dimensional coronary artery anatomy. Blood flow simulations were performed, and endothelial shear stress(ESS) distribution was estimated for each scaffolded segment. In a linear mixed-effect model, the contributing factors for low (<1.0Pa) ESS levels were assessed. At 30-day post-implantation, histopathological assessment was performed at 2 scaffolds. Results In scaffolded segments, the median ESS was 0.57 (IQR: 0.29–0.99) Pa. In linear mixed-effect analysis, cross-section area was associated with low shear stress levels. In scaffolded segments, the percentage of the recirculation zone per scaffolded luminal surface was 3.26±2.07%. At 30-day histopathological assessment of implanted vessel segments revealed minimal injury score, minimal neointimal inflammation and minimal adventitial inflammation scores with moderate endothelial coverage. Fibrin accumulation was seen at 95.69±2.47% of the struts. Conclusion The thick rectangular strut design of the Absorb BVS incited flow disruptions with low shear stress inducing fibrin accumulation. CFD assessment can be used to guide improvements in the scaffold design for a more “hemo-compatible” geometry.

AIMS The Absorb bioresorbable vascular scaffold (BVS) has high rates of target lesion failure (TLF) at three years. Low wall shear stress (WSS) promotes several mechanisms related to device TLF. We investigated the impact of BVS compared to XIENCE V (XV) on coronary WSS after device deployment. METHODS AND RESULTS In the prospective, randomised, controlled ABSORB III Imaging study (BVS [n=77] or XV [n=36]), computational fluid dynamics were performed on fused angiographic and intravascular ultrasound (IVUS) images of post-implanted vessels. Low WSS was defined as <1 Pa. There were no differences in demographics, clinical risks, angiographic reference vessel diameter or IVUS minimal lumen diameter between BVS and XV patients. A greater proportion of vessels treated with BVS compared to XV demonstrated low WSS across the whole device (BVS: 17/77 [22%] vs XV: 2/36 [6%], p<0.029). Compared to XV, BVS demonstrated lower median circumferential WSS (1.73 vs 2.21 Pa; p=0.036), outer curvature WSS (p=0.026), and inner curvature WSS (p=0.038). Similarly, BVS had lower proximal third WSS (p=0.024), middle third WSS (p=0.047) and distal third WSS (p=0.028) when compared to XV. In a univariable logistic regression analysis, patients who received BVS were 4.8 times more likely to demonstrate low WSS across the scaffold/stent when compared to XV patients. Importantly, in a multivariable linear regression model, hypertension (beta: 0.186, p=0.023), lower contrast frame count velocity (beta: -0.411, p<0.001), lower post-stent residual plaque burden (beta: -0.338, p<0.001), lower % underexpanded frames (beta: -0.170, p=0.033) and BVS deployment (beta: 0.251, p=0.002) remained independently associated with a greater percentage of stented coronary vessel areas exposed to low WSS. CONCLUSIONS In this randomised controlled study, the Absorb BVS was 4.8 times more likely than the XV metallic stent to demonstrate low WSS. BVS implantation, lower blood velocity and lower residual post-stent plaque burden were independently associated with greater area of low WSS.

No abstract is provided for this article.

<b>Rationale:</b> Pulmonary fibroblasts proliferate and produce extracellular matrix to repair the lung environment. In COPD, parenchymal-derived fibroblasts exhibit reduced proliferation possibly due to growth arrest via cellular senescence. However, the proliferative capabilities of small airway fibroblasts (SAF) are unknown. <b>Aim:</b> To investigate the proliferative capacity of SAF from COPD patients and age-matched non-smoker and smoker controls. <b>Method:</b> SAF were isolated from surgical lung resections from non-smokers, smokers and COPD patients. iCELLigence technology and propidium iodide (PI) staining were used to investigate SAF proliferation and phase of cell cycle arrest, respectively. Senescence was identified using Senescence Associated-β-Galactosidase (SA-β-Gal) staining and potential mechanisms studied by qPCR for gene expression of cell cycle checkpoints. <b>Results:</b> SAF from COPD patients showed significantly reduced proliferation rate compared to non-smokers and smokers (p&lt;0.05 and p&lt;0.001 respectively, n=4-7). PI staining suggested more COPD SAF were G1 phase arrested compared to NS SAF (p&lt;0.01), and fewer in G2 (p&lt;0.05, n=4-5). Senescence could be driving this, since more COPD SAF stained positive for SA-β-Gal compared to non-smokers (21% vs 11%, p&lt;0.05, n=4-5). However, there was no change in p21, p16, p27 or CDK4 expression; but a trend in increased p15 (+116%, p=0.28) and p53 (+44%, p&lt;0.05, n=7-11) expression. <b>Conclusion:</b> These data suggest COPD SAF display reduced proliferation compared to controls, arresting in G1 phase. This may be due to senescence, induced by p15 and p53. Further investigation into cell cycle arrest mechanisms in COPD may provide alternative targets for therapeutics.

The contribution of neutrophils to the action of endotoxin on plasma exudation in the airways of anaesthetized guinea-pigs was quantified by measuring the extravasation of Evans blue dye. Endotoxin (Salmonella enteritidis) caused a dose-dependent increase in microvascular leakage to Evans blue dye which was maximal after 25 min (p less than 0.05). The minimum dose tested that induced a significant rise in leakage was 1.5 mg.kg-1 for "central" intrapulmonary airways (ipa); 4.5 mg.kg-1 for trachea and main bronchi and 7.5 mg.kg-1 for nasal mucosa, larynx and "peripheral" ipa. Depletion of circulating neutrophil numbers by 97% using an antibody to guinea-pig neutrophils caused no significant diminution of the effects of endotoxin on leakage in any part of the airway. There was no significant influx of neutrophils into the airway interstitium at the time of maximum extravasation of Evans blue. We conclude that endotoxin-induced airway microvascular permeability is dependent upon mechanisms other than circulating neutrophils.

Few studies are available on magnetic navigation system (MNS) for coronary artery disease. The present investigation was conducted to evaluate the feasibility and safety of guidewire navigation with a MNS in diseased coronary arteries.Between February 2004 and August 2005, a total of 59 patients (68 target vessels) underwent magnetic-assisted guidewire navigation in coronary arteries with stenoses amenable to coronary intervention. Patients were excluded if any of the following conditions applied: pacemakers or cardioverter defibrillator implanted; acute myocardial infarction; thrombotic lesions; chronic total occlusion; claustrophobia; and renal dysfunction with serum creatinine > 2.5mg/dl. Procedural success was defined as successful guidewire passage distal to the stenoses with no procedural events, defined as either perforation or dissection. Magnetic guidewires successfully crossed 60 (88%) lesions. Only 1 patient experienced a minor dissection of vessel wall in a circumflex lesion and was treated with a coronary stent. There was no other complication related to the magnetic guidewire. Nineteen (27.3%) coronary interventions were performed with magnetic guidewires. In 4 complex lesions (a lesion located in saphenous vein graft with proximal severe tortuosity; 3 approaches to stent-jailed side branch), where conventional wires failed to cross the culprit lesions, magnetic navigation achieved successful guidewire passage.Guidewire navigation using a MNS was feasible and safe. In the four complex cases, magnetic navigation enabled crossing of lesions in which conventional attempts failed. Further studies are needed to better evaluate the efficacy of MNS compared with conventional manual navigation.

This study aims to evaluate the acute effects of an oscillating positive expiratory pressure device (flutter) on airways resistance in patients with chronic obstructive pulmonary disease (COPD). Randomized crossover study: 15 COPD outpatients from Asthma Lab–Royal Brompton Hospital underwent spirometry, impulse oscillometry (IOS) for respiratory resistance (R) and reactance (X), and fraction exhaled nitric oxide (FeNO) measures. Thirty minutes of flutter exercises: a "flutter-sham" procedure was used as a control, and airway responses after a short-acting bronchodilator were also assessed. Respiratory system resistance (R): in COPD patients an increase in X5insp (−0.21 to −0.33 kPa/L/s) and Fres (24.95 to 26.16 Hz) occurred immediately after flutter exercises without bronchodilator. Following 20 min of rest, a decrease in the R5, ΔR5, R20, X5, and Ax was observed, with R5, R20, and X5 values lower than baseline, with a moderate effect size; there were no changes in FeNO levels or spirometry. The use of flutter can decrease the respiratory system resistance and reactance and expiratory flow limitation in stable COPD patients with small amounts of secretions.