Publications

Atherosclerotic plaques develop in low shear stress regions. In the more advanced phase of the disease, plaques are exposed to altered shear stress levels, which could influence plaque composition. We investigated changes in plaque composition in human coronary arteries over a 6-month period and how these changes are related to shear stress.We took images of eight coronary arteries to obtain the 3D shape of the arteries. Lumen data were combined with computational fluid dynamics to obtain shear stress. Palpography was applied to measure strain at baseline and at 6-month follow-up. The change in strain from baseline to follow-up served as a marker for the change in plaque composition. We identified 17 plaques, and each plaque was divided into four regions: the upstream, throat, shoulder and downstream region. Shear stress and strain in the downstream region was significantly lower than in the other regions. There was no significant change in strain for the four different plaque regions. However, we observed that those plaque regions exposed to high shear stress showed a significant increase in strain.Plaque regions exposed to high shear stress showed an increase in strain over time. This indicates that shear stress may modulate plaque composition in human coronary arteries.

The impact of an occluded right coronary artery (RCA) in patients with left main coronary artery disease (LMCAD) undergoing revascularisation is unknown. We compared outcomes for patients with LMCAD randomised to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) according to the presence of an occluded RCA in the EXCEL trial.The EXCEL trial randomised 1,905 patients with LMCAD and SYNTAX scores ≤32 to PCI with everolimus-eluting stents versus CABG. Patients were categorised according to whether they had an occluded RCA at baseline, and their outcomes were examined using multivariable Cox proportional hazards regression. The primary endpoint was a composite of death, stroke, or myocardial infarction at three years. Among 1,753 patients with a dominant RCA by core laboratory analysis, the RCA was occluded in 130 (7.4%) at baseline. PCI was attempted in 34 of 65 patients with an occluded RCA (52.3%) and was successful in 27 (79.4% of those attempted; 41.5% of all RCAs recanalised). The RCA was bypassed in 42 of 65 patients with an occluded RCA (64.6%; p=0.0008 versus PCI). The three-year absolute and relative rates of the primary endpoint were similar between PCI and CABG, in patients with or without an occluded RCA (pinteraction=0.92).In the EXCEL trial, the presence of an occluded RCA at baseline did not confer a worse three-year prognosis in patients undergoing revascularisation for LMCAD and did not affect the relative outcomes of PCI versus CABG in this high-risk patient cohort.

Objectives This study sought to evaluate the diagnostic accuracy of 64-slice multislice computed tomography (MSCT) coronary angiography in the follow-up of patients with previous coronary stent implantation. Background Recent investigations have shown increased image quality and diagnostic accuracy for noninvasive coronary angiography with 64-slice MSCT as compared with previous-generation MSCT scanners, but data on the evaluation of coronary stents are scarce. Methods In 182 patients (152 [84%] male, ages 58 ± 11 years) with previous stent (≥2.5 mm diameter) implantation (n = 192), 64-slice MSCT angiography using either a Sensation 64 (Siemens, Forchheim, Germany) or Aquilion 64 (Toshiba, Otawara, Japan) was performed. At each center, coronary stents were evaluated by 2 experienced observers and evaluated for the presence of significant (≥50%) in-stent restenosis. Quantitative coronary angiography served as the standard of reference. Results A total of 14 (7.3%) stented segments were excluded because of poor image quality. In the interpretable stents, 20 of the 178 (11.2%) evaluated stents were significantly diseased, of which 19 were correctly detected by 64-slice MSCT. Accordingly, sensitivity, specificity, and positive and negative predictive value to identify in-stent restenosis in interpretable stents were 95.0% (95% confidence interval [CI] 85% to 100%), 93.0% (95% CI 90% to 97%), 63.3% (95% CI 46% to 81%), and 99.3% (95% CI 98% to 100%), respectively. Conclusions In-stent restenosis can be evaluated with 64-slice MSCT with good diagnostic accuracy. In particular, a high negative predictive value of 99% was observed, indicating that 64-slice MSCT may be most valuable as a noninvasive method of excluding in-stent restenosis.

Objectives This study sought to investigate the impact of nonemergent, uncomplicated target lesion revascularization (TLR) on the risk of long-term mortality after percutaneous coronary intervention (PCI). Background Restenosis requiring TLR after PCI is generally considered a benign event. Methods The study pooled patient-level data from 21 randomized trials. Subjects dying the same day as or the day after the TLR procedure as well as those with myocardial infarction (MI) the day before, the same day as or the day after TLR were excluded. The primary endpoint of the study was all-cause mortality. Results The dataset included 32,524 patients who were stratified according to whether repeat TLR was performed during follow-up. During a median follow-up of 37 months, 2,330 (7.2%) patients underwent a nonemergent, uncomplicated TLR procedure. After adjusting for potential confounders, TLR was an independent predictor of mortality (hazard ratio: 1.23, 95% confidence interval: 1.04 to 1.45; p = 0.02). Patients undergoing nonemergent, uncomplicated TLR had significantly higher rates of non–procedure-related MI compared with those without TVR. Among patients undergoing elective TLR, MI occurring after TLR was an independent predictor of mortality (hazard ratio: 3.82; 95% confidence interval: 2.44 to 5.99; p < 0.0001). Conclusions Nonemergent, uncomplicated TLR after PCI is an independent predictor of long-term mortality, an association in part explained by higher rates of MI occurring after TLR. Efforts aimed at reducing TLR risk may translate into prognostic benefits including reduced rates of MI and survival.

<b>Background</b>: Inhalation of aerosol particles from the environmental air, (natural and industrial sources) results in the deposition of potentially hazardous particulate substances in the human respiratory tract. Recent evidence has shown an increase in adult and childhood leukaemia risk near high-voltage power lines (HVPL). This may be explained by ultrafine particles of air pollution becoming electrostatically charged through contact with corona ions emitted by the power lines. <b>Aim</b>: We investigated the hypothesis that particles with excess charge have a higher probability of human lung deposition than 9charge-neutralised9 particles. <b>Methods</b>: We developed and characterized an ultrafine particle generation and delivery system in order to investigate the lung deposition of positively (CP) and neutrally charged (CN) 100nm particles in eight healthy adult subjects. The primary outcome measure was penetration index (PI), a measure of aerosol lung deposition and penetration relative to an inert gas (Krypton). The particle number deposition efficiency (DFp) was also measured. <b>Results:</b> PI and DFp were identical for both charged and uncharged particles (Table). This indicates that the mechanism of electrostatically-enhanced deposition did not have a measurable effect on particle lung deposition in adults and our results are contrary to the corona ion hypothesis. <b>Conclusion:</b> Corona ions from HVPL may not be a key determinant influencing adult and childhood hemato-oncological risk.

In recent years, there has been increasing interest in noninvasive monitoring of airway inflammation and oxidative stress. Several volatile and nonvolatile substances can be measured in exhaled breath and have been suggested as potential biomarkers of these events. Exhaled gases, including carbon monoxide (CO), alkanes (ethane, pentane), and substances measured in breath condensate, such as hydrogen peroxide (H 2 O 2 ) and isoprostanes were all suggested as potential markers of oxidative stress in the lung. A European Respiratory Society (ERS) International Research Seminar entitled “Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases” was organized by the Airway Regulation and Provocation Group of the Clinical Allergy and Immunology Assembly in Budapest, Hungary in September, 1999 to integrate the latest knowledge on these issues and accelerate further improvement in this area. During this 2-day event several issues were raised about: the use and standardization of measurements in exhaled breath; problems of measuring expired H 2 O 2 and other mediators in breath condensate; role and regulation of haemoxygenase (HO)-1 in the lung; and conditions and factors influencing exhaled CO. This report is a summary of the main presentations at the seminar, together with the current areas of research in this rapidly expanding field.

Quantitative coronary angiography (QCA) analysis for bifurcation lesions needs to be standardized.In vitro validation of two models for bifurcation QCA segmental analysis.In the latest edition of the Cardiovascular angiography analysis system (CAAS 5v8, Pie Medical Imaging, Maastricht, The Netherlands) a 6-segment model for two-dimensional coronary bifurcation analysis was implemented next to the currently available 11-segment model. Both models were validated against 6 precision manufactured plexiglas phantoms, each of them mimicking a vessel with three successive bifurcation lesions with variable anatomy and Medina class. The phantoms were filled with 100% contrast agent and imaged with a biplane gantry. Images acquired in antero-posterior (AP) direction by either C-arm and at 30° right and left anterior oblique angulation were analyzed by two independent analysts, blinded to the actual dimensions. Manual correction of the contours was not allowed. Measurements for minimal lumen diameter (MLD), reference vessel diameter (RVD), percent diameter stenosis (DS) and bifurcation angle (BA) were compared with the true phantom dimensions.In AP views the accuracy and precision (mean difference ± SD) of 11- and 6-segment model for MLD, RVD, and DS were 0.065 ± 0.128 mm vs. 0.058 ± 0.142 mm, -0.021 ± 0.032 mm vs. -0.022 ± 0.030 mm, and -2.45% ± 5.07% vs. -2.28% ± 5.29%, respectively. Phantom MLD values ≤ 0.7 mm were systematically overestimated; if excluded, MLD accuracy and precision became 0.015 ± 0.106 mm and 0.004 ± 0.125 mm for the 11- and 6-segment model, respectively. Accuracy and precision for BA were -2.2° ± 3.3°. Interobserver variability for MLD, RVD, DS, and BA for either model was ≤ 0.049 mm, ≤ 0.056 mm, ≤ 2.77%, and 1.6°, respectively. Agreement between models for MLD, RVD, and DS was ± 0.079 mm, ± 0.011 mm, and ± 2.07%. Accuracy and precision for diameter-derived parameters were slightly decreased in angulated projections; precision for BA measurements dropped to 6.1°.The results of both models are highly reproducible and for phantom MLD values >0.7 mm in excellent agreement with the true dimensions.