Publications

Restenosis after coronary angioplasty: The paradox of increased lumen diameter and restenosis

Restenosis after coronary angioplasty is the single complication that most limits this revascularization procedure in clinical practice. The process is largely unpredictable and the lesion-related factors predisposing to restenosis are poorly understood, with little consensus in published reports. In this study using detailed quantitative angiographic measurements to assess 490 lesions, the simple lesion characteristics associated with restenosis were defined and the relation to the restenosis process documented. Restenosis was defined as an absolute deterioration in the minimal lumen diameter by ≥ 0.72 mm, a criterion based on the 95% confidence intervals for repeat angiographic measurements. This was chosen in an attempt to separate spurious changes due to a poor angiographic result and the variability of angiographic measurements from significant changes due to the restenosis process. The principal determinants of restenosis were found to be a large improvement in the minimal lumen diameter at the time of dilation (1.13 mm for the restenosis group compared with 0.86 mm for the no restenosis group [p < 0.0001]) and an optimal postangioplasty result (minimal lumen diameter 2.28 mm in the restenosis group compared with 2.05 mm [p < 0.001] in the no restenosis group, corresponding to a 25% and a 30% diameter stenosis, respectively [p < 0.0001]). These observations reported for the first time suggest that the distinction needs to be made between a “clinical restenosis” of ≥ 50% diameter stenosis and the “restenosis process” as measured by the absolute changes occurring during and after angioplasty. They lend support to the hypothesis that the degree of mechanical stretch produced by the dilating balloon on the vessel wall may be important in stimulating the restenosis process. This is in contradiction to deductions obtained if restenosis is based on “clinical restenosis,” which suggests that restenosis is associated primarily with a poor angioplasty result. More important, it indicates that there is potential for misinterpreting the results of restenosis studies if the observations are based solely on conventional restenosis criteria without knowledge of the absolute changes occurring during and after the angioplasty procedure.

Optimal prestressing of triple-bay prestressed stayed columns

Cardiac catheterization under echocardiographic control in a pregnant woman

A 22 year old woman had signs of rheumatic mitral and aortic valve disease early in pregnancy. Cardiac catheterization was performed during her third month of pregnancy under two-dimensional echocardiographic control without the use of ionizing radiation. Severe mitral stenosis with mild aortic stenosis was found. Five cubic centimeters of 5 percent dextrose in water were injected by hand to obtain left ventriculograms and supravalvular aortograms of sufficient quality to diagnose valvular regurgitation. The use of “echo-catheterization” may have significant advantages in selected clinical situations.

A NEW TOOL FOR THE RISK STRATIFICATION OF PATIENTS WITH COMPLEX CORONARY ARTERY DISEASE: THE CLINICAL SYNTAX SCORE

No abstract is provided for this article.

Dual antiplatelet therapy, drug-eluting stents and bioresorbable vascular scaffolds: Evolutionary perspectives

Dual antiplatelet therapy reduces the risk of myocardial infarction, stent thrombosis, and cardiovascular mortality after percutaneous coronary intervention, but the optimal duration of therapy remains unclear. Stent thrombosis, one of the most feared complications of coronary intervention, is associated with high mortality and morbidity and is related in part to technical and patient-specific factors. Advances in device technology and better understanding of the pathophysiology of stent thrombosis have reduced the frequency of this devastating complication. Bioresorbable vascular scaffolds possess a number of advantageous features and are currently undergoing active investigation. Bioresorbable vascular scaffolds have been demonstrated to restore physiologic vasomotion, allow for late lumen enlargement, and upon full resorption remove the nidus for very late polymer reactions and resolve concerns of stent malapposition and side branch jailing. Based on the results from recent large-scale randomized trials, the optimal duration of dual antiplatelet therapy may depend on the choice of device type, as well as the individual patient risk of ischemic versus hemorrhagic complications.

Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma.

Inhaled anticholinergic drugs are effective in the treatment of chronic obstructive pulmonary diseases (COPD), of acute asthma, and of some patients with nocturnal asthma. Tiotropium bromide (tiotropium) is a novel anticholinergic agent with a long duration of action and kinetic selectivity for M1- and M3-subtypes of muscarinic receptors. We investigated the duration of protection of a single dose of inhaled tiotropium against methacholine-induced bronchoconstriction in 12 male atopic asthmatic volunteers in a double-blind, placebo-controlled study. On four separate occasions 8 to 24 d apart, methacholine PC20 was measured serially for up to 48 h after placebo and after three doses of tiotropium (10, 40, and 80 microg). Each dose of tiotropium produced mild bronchodilatation as measured by an increase in FEV1 of between 5.5 and 11.1% from baseline, that was sustained for 24 h. There was significant dose-dependent protection against methacholine challenge at 2 h of 5.0 +/- 1.1, 7.1 +/- 0.5, and 7.9 +/- 0.7 (mean +/- SEM) doubling doses after 10, 40, and 80 microg respectively, and this persisted for 48 h. There were no adverse effects reported at any dose. The prolonged bronchodilator response and protection against methacholine challenge suggest that tiotropium may be useful in the treatment of COPD and nocturnal asthma and that once-daily dosing may be sufficient.

Strength enhancement of the corner regions of stainless steel cross-sections

Stability of steel beams using the continuous strength method

Potential Novel Therapies for Chronic Obstructive Pulmonary Disease

While considerable progress has been made in development of drugs for asthma, there have been few advances in the treatment of chronic obstructive pulmonary disease (COPD). New therapeutic approaches to prevent disease progression are urgently needed and these will arise out of better understanding of the disease process at a cell and molecular level. The inflammatory response in COPD differs markedly from that of asthma, with differences in inflammatory cells, mediators and response to therapy. The neutrophilic inflammation is orchestrated by chemotactic factors, such as interleukin (IL)-8, other CXC chemokines and leukotriene B4; receptor blockers (CXCR1, CXCR2, BLT antagonists) or synthesis inhibitors (5'-lipoxygenase inhibitors) might be effective. Tumour necrosis factor (TNF) alpha may be an important amplifying cytokine and there are several strategies for blocking it (antibodies, soluble receptors, TACE inhibitors). IL-10 is effective in blocking the synthesis of IL-8 and TNF alpha as well as proteases. Oxidative stress and peroxynitrite may be important in COPD; more effective antioxidants are now in development. The inflammatory response in COPD is essentially steroid-resistant so that alternative anti-inflammatory treatments are needed. Phosphodiesterase 4 inhibitors look promising in early clinical studies. Nuclear factor-kappa B inhibitors and p38 MAP kinase inhibitors may also be effective. Several protease inhibitors are in development including those for neutrophil elastase, selective matrix metalloproteinase and cathepsin.

Review Th2 cytokines and asthma: an introduction

Asthma is a highly complex disease that is still poorly understood and whose cause remains unknown. One of the striking advances in the last decade has been the recognition that cytokines play a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. Indeed the increased and abnormal expression of cytokines in airway cells is one of the major targets of corticosteroid therapy, by far the most effective controller treatment for asthma currently available. Many cytokines and chemokines are involved in the pathophysiology of asthma [1,2]. While some of these cytokines, such as interleukin (IL)-1, tumour necrosis factor-α and IL-6, are involved in many inflammatory diseases, including chronic obstructive pulmonary disease, rheumatoid arthritis and inflammatory bowel disease, others are more specific

Preclinical assessment of transcatheter-delivered expandable endoluminal polymeric graft fabricated by electrospinning of microfiber

Background Matrix fabricated from electrospinning of micro fibre of polyester is porous and permeable to blood, facilitates cell infiltration and late resorption of the biodegradable material. This biomaterial opens an avenue of research in recreating a novel and favourable endoluminal lining in diseased vessel. Previous preclinical work has shown that implants in aorta of rodents generate layers of endoluminal elastin. In humans, one of the most impervious arteries to atherosclerosis is the intra-thoracic artery; therefore, an attempt to induce similar structures with an implantable device was made. Methods For this study, novel tissue-engineered vascular grafts (T-TEVGs) were used in a preclinical rabbit iliac artery model. It was made of resorbable polyester biomaterial processed into fibrous tubular conduits. These T-TEVGs were implanted percutaneously. In total, twelve T-TEVGs in iliac arteries of nine rabbits were implanted. Follow-up were conducted on five rabbits with eight T-TEVGs at three months, two rabbits with two T-TEVGs at six months, and two rabbits with two T-TEVGs at twelve months. At follow-up, percutaneous optical coherence tomography (OCT) was performed, and OCT-derived luminal vessel wall dimensions and fractional flow reserve (OFR) derived from OCT were assessed. Results The overall pooled analysis at different timepoints on follow-up, documented an average MLA of 1.74±0.48mm2, average of proximal and distal reference area of 4.55±0.99 mm2, average area stenosis of 61±12%, and mean OFR value of 0.96±0.03 (OFR ranging from 0.89 to 0.99). There was a moderate positive correlation between minimum lumen area and OFR (r=0.590, p&amp;lt; 0.01). There was a strong negative correlation between percentage area stenosis and OFR (r= - 0.846, p&amp;lt; 0.01). At no timepoint in follow-up and in every vessel analysed, OFR value was lower than 0.89, suggesting that none of these vessels exhibited flow-limiting narrowing. Our study has a few limitations. 1) The preclinical model is a non-atherosclerotic rabbit; 2) There was no barotrauma prior to the implantation of the device; 3) Limited sample size, short and medium follow-up duration, and pooling of assessment at different timepoints. Conclusion The current study shows the durability and favourable hemodynamics of this bioresorbable fibrillated scaffold at short and medium term follow-up, supporting the potential utility of T-TEVEGs for peripheral human artery revascularisation. Long-term follow-ups are mandatory to confirm the durability of these results. Histopathology of this preclinical model should confirm the endoluminal elastin as previously documented in rodents (rats) and will be presented at the time of the congress.

3-Dimensional Bifurcation Angle Analysis in Patients With Left Main Disease

Objectives We explore the bifurcation angle (BA) parameters of the left main coronary artery (LM), the effect of percutaneous coronary intervention (PCI) on this angulation, and the impact of BA on clinical outcome. Background The BA is emerging as a predictor of outcome after PCI of bifurcation lesions. Three-dimensional (3D) quantitative coronary angiography (QCA) overcomes the shortcomings of 2-dimensional analysis and provides reliable data. Methods This is a substudy of the SYNTAX (SYNergy Between Percutaneous Coronary Intervention With TAXus and Cardiac Surgery) trial. The cineangiograms of the 354 patients who underwent PCI of their LM stem were analyzed with 3D QCA software (CardiOp-B, Paieon Medical, Ltd., Rosh Ha'ayin, Israel). The proximal BA (between LM and left circumflex [LCX]) and the distal BA (between left anterior descending and LCX) were computed in end-diastole and end-systole, both before and after PCI. The cumulative major adverse cardiac and cardiovascular event (MACCE) rates throughout the 12-month period after randomization were stratified across pre-PCI distal BA values and compared accordingly. Results Complete analysis was feasible in 266 (75.1%) patients. Proximal and distal BA had mean pre-PCI end-diastolic values of 105.9 ± 21.7° and 95.6 ± 23.6°, respectively, and were inversely correlated (r = −0.75, p < 0.001). During systolic motion of the heart there was an enlargement of the proximal angle and a reduction of the distal angle (ΔBA −8.2° and 8.5°, respectively, p < 0.001 for both). The PCI resulted in a mean decrease in the distal BA (ΔBA 4.5°, p < 0.001). The MACCE rates did not differ across distal BA values; freedom from MACCE at 12 months was 82.8%, 85.4%, and 81.1% (p = 0.74) for diastolic values (first through third tertile). Conclusions Left main BA analysis with 3D QCA is feasible. Both proximal and distal angles are affected by cardiac motion; PCI modifies the distal angle. There is no clear difference in event rates across pre-PCI distal BA values.

IL-9-producing cells promote Th1 responses against Mycobacterium tuberculosis. (P3015)

Abstract IFNγ-secreting cells are critical in the defense against M. tuberculosis (Mtb) infection, but other cells might be required to eradicate the pathogen. IL-9-producing cells were reported to be involved in inflammation and immune diseases, but their role during tuberculosis remains to be clarified. Here we analyzed the involvement of IL-9-secreting cells in the immunity of patients with active disease. We demonstrated that Mtb induced a marked expansion of CD4 IL-9+ cells in peripheral blood from tuberculosis patients. After antigen stimulation, patients with robust Th1 responses to Mtb (high responders) produced higher amounts of IL-9 compared to those with weak Th1 responses (low responders) and a direct significant correlation between IL-9 and IFNγ production against Mtb was detected. To investigate the role of the IL-9 secreted by those lymphocytes, we inhibited IL-9 expression with siRNA, which significantly diminished the production of IFNγ against Mtb. Addition of IL-9 markedly increased the secretion of IFNγ against Mtb, even in low responders. Furthermore, treatment with IL-9 inhibited Mtb-induced apoptosis of IFNγ+ cells, enhancing the survival of the cells. Finally, by studying the effect of neutralizing IL-9 antibodies on polarized Th9 cells, we confirmed that IL-9 participates in the up-regulation of IFNγ production against Mtb. Thus, our results indicate that IL-9 enhances Th1 responses during tuberculosis promoting the cell-mediated immunity to the pathogen.

Clinical Studies on New Drugs

Optical coherence tomography (OCT) in secondary revascularisation: stent and graft assessment.

Optical coherence tomography is a recently introduced intracoronary imaging modality with higher spatial resolution than intravascular ultrasound. For this reason, it is increasingly applied to investigate the characteristics of vulnerable atheromatous plaques and the result of stent implantation, struts coverage and restenosis, as well as in procedural decision-making. OCT is also useful in the field of secondary revascularisation, particularly in assessing implanted stents, evaluating relevant technologies like biodegradable stents, and in studying surgical grafts. In this article we perform a review of current developments and evidence in this area.

Rebuttal From Dr Barnes

Experimental investigation and design of slip resistant aluminium alloy–stainless​ steel connections

An Inverse Method for Imaging the Local Elasticity of Atherosclerotic Coronary Plaques

The rupture of thin-cap fibroatheroma (TCFA) plaques is a major cause of acute coronary events. A TCFA has a trombogenic soft lipid core, shielded from the blood stream by a thin, possibly inflamed, stiff cap. The majority of atherosclerotic plaques resemble a TCFA in terms of overall structural composition, but have a more complex, heterogeneous morphology. An assessment of the material distribution is vital for quantifying the plaque's mechanical stability and for determining the effect of plaque-stabilizing pharmaceutical agents. We describe a new automated inverse elasticity method, intravascular ultrasound (IVUS) modulography, which is capable of reconstructing a heterogeneous Young's modulus distribution. The elastogram (i.e., spatial strain distribution) of the plaque is the input for the method, and is measured using the clinically available technique, IVUS elastography. Our method incorporates a novel divide-and-conquer strategy, allowing the reconstruction of TCFAs as well as heterogeneous plaques with localized regions of soft, weakened tissue. The method was applied to ex vivo elastograms, which were simulated from the cross sections of postmortem human coronary plaques. To demonstrate the clinical feasibility of the method, measured elastograms from human atherosclerotic coronary arteries were analyzed. One elastogram was measured in vitro; the other, in vivo . The method approximated the true Young's modulus distribution of all simulated plaques, while the in vitro reconstruction was in agreement with histology. In conclusion, the IVUS modulography in combination with the IVUS elastography has strong potential to become an all-encompassing modality for detecting plaques, for assessing the information related to their rupture-proneness, and for imaging their heterogeneous elastic material composition.