Nanomedicine for the reduction of the thrombogenicity of stent coatings

The treatment of patients with drug-eluting stents (DES) continues to evolve with the current emergence of DES technology that offers a combination of pharmacological and mechanical approaches to prevent arterial restenosis. However, despite the promising short-term and mid-term outcomes of DES, there are valid concerns about adverse clinical effects of late stent thrombosis. In this study, we present an example of how nanomedicine can offer solutions for improving stent coating manufacturing, by producing nanomaterials with tailored and controllable properties. The study is based on the exploitation of human platelets response towards carbon-based nanocoatings via atomic force microscope (AFM). AFM can facilitate the comprehensive analysis of platelets behavior onto stent nanocoatings and enable the study of thrombogenicity. Platelet-rich plasma from healthy donors was used for the real-time study of biointerfacial interactions. The carbon nanomaterials were developed by rf magnetron sputtering technique under controllable deposition conditions to provide favorable surface nanotopography. It was shown that by altering the surface topography of nanocoatings, the activation of platelets can be affected, while the carbon nanocoatings having higher surface roughness were found to be less thrombogenic in terms of platelets adhesion. This is an actual solution for improving the stent coating fabrication

Centre of pressure, vertical ground reaction forces and neuromuscular responses of special-forces soldiers to 43km load carriage in the field

The primary purpose of this study was to examine lateral deviations in centre of pressure as a result of an extreme duration load carriage task, with particular focus on heel contact. Twenty (n=17 males, n=3 females) soldiers from a Special Operation Forces unit (body mass: 80.72±21.49kg; stature:178.25±8.75cm; age: 26±9yrs) underwent gait plantar pressure assessment and vertical jump testing before and after a 43km load carriage event (duration 817.02[32.66]min) carrying a total external load of 29.80 (1.05)kg. Vertical jump height decreased by 18.62%±16.85% (0.30±0.08m to 0.24±0.07m) p<.001. Loading peak and mid stance force minimum were significantly increased after load carriage (2.59±0.51BW vs. 2.81±0.61BW; p=.035; dGlass=0.44 and 1.28±0.40BW vs. 1.46±0.41BW; p=.015 dGlass=0.45, respectively) and increases in lateral centre of pressure displacement were observed as a result of the load carriage task 14.64±3.62mm to 16.97 ±3.94mm p<.029. In conclusion, load carriage instigated a decrease in neuromuscular function alongside increases in ground reaction forces associated with injury risk and centre of pressure changes associated with ankle sprain risk. Practitioners should consider that possible reduction in ankle stability remains even once the load had been removed, suggesting soldiers are still at increased risk of injury even once the load has been removed

Texture Analysis and Radial Basis Function Approximation for IVUS Image Segmentation

>Intravascular ultrasound (IVUS) has become in the last years an important tool in both clinical and research applications. The detection of lumen and media-adventitia borders in IVUS images represents a first necessary step in the utilization of the IVUS data for the 3D reconstruction of human coronary arteries and the reliable quantitative assessment of the atherosclerotic lesions. To serve this goal, a fully automated technique for the detection of lumen and media-adventitia boundaries has been developed. This comprises two different steps for contour initialization, one for each corresponding contour of interest, based on the results of texture analysis, and a procedure for approximating the initialization results with smooth continuous curves. A multilevel Discrete Wavelet Frames decomposition is used for texture analysis, whereas Radial Basis Function approximation is employed for producing smooth contours. The proposed method shows promising results compared to a previous approach for texture-based IVUS image analysis

Low-density lipoprotein concentration in the normal left coronary artery tree

<p>Abstract</p> <p>Background</p> <p>The blood flow and transportation of molecules in the cardiovascular system plays a crucial role in the genesis and progression of atherosclerosis. This computational study elucidates the Low Density Lipoprotein (LDL) site concentration in the entire normal human 3D tree of the LCA.</p> <p>Methods</p> <p>A 3D geometry model of the normal human LCA tree is constructed. Angiographic data used for geometry construction correspond to end-diastole. The resulted model includes the LMCA, LAD, LCxA and their main branches. The numerical simulation couples the flow equations with the transport equation applying realistic boundary conditions at the wall.</p> <p>Results</p> <p>High concentration of LDL values appears at bifurcation opposite to the flow dividers in the proximal regions of the Left Coronary Artery (LCA) tree, where atherosclerosis frequently occurs. The area-averaged normalized luminal surface LDL concentrations over the entire LCA tree are, 1.0348, 1.054 and 1.23, for the low, median and high water infiltration velocities, respectively. For the high, median and low molecular diffusivities, the peak values of the normalized LDL luminal surface concentration at the LMCA bifurcation reach 1.065, 1.080 and 1.205, respectively. LCA tree walls are exposed to a cholesterolemic environment although the applied mass and flow conditions refer to normal human geometry and normal mass-flow conditions.</p> <p>Conclusion</p> <p>The relationship between WSS and luminal surface concentration of LDL indicates that LDL is elevated at locations where WSS is low. Concave sides of the LCA tree exhibit higher concentration of LDL than the convex sides. Decreased molecular diffusivity increases the LDL concentration. Increased water infiltration velocity increases the LDL concentration. The regional area of high luminal surface concentration is increased with increasing water infiltration velocity. Regions of high LDL luminal surface concentration do not necessarily co-locate to the sites of lowest WSS. The degree of elevation in luminal surface LDL concentration is mostly affected from the water infiltration velocity at the vessel wall. The paths of the velocities in proximity to the endothelium might be the most important factor for the elevated LDL concentration.</p

Clinical validation of an algorithm for rapid and accurate automated segmentation of intracoronary optical coherence tomography images

Objectives: The analysis of intracoronary optical coherence tomography (OCT) images is based on manual identification of the lumen contours and relevant structures. However, manual image segmentation is a cumbersome and time-consuming process, subject to significant intra- and inter-observer variability. This study aims to present and validate a fully-automated method for segmentation of intracoronary OCT images. Methods: We studied 20 coronary arteries (mean length = 39.7 ± 10.0 mm) from 20 patients who underwent a clinically-indicated cardiac catheterization. The OCT images (n = 1812) were segmented manually, as well as with a fully-automated approach. A semi-automated variation of the fully-automated algorithm was also applied. Using certain lumen size and lumen shape characteristics, the fully- and semi-automated segmentation algorithms were validated over manual segmentation, which was considered as the gold standard. Results: Linear regression and Bland–Altman analysis demonstrated that both the fully-automated and semiautomated segmentation had a very high agreement with the manual segmentation, with the semi-automated approach being slightly more accurate than the fully-automated method. The fully-automated and semiautomated OCT segmentation reduced the analysis time by more than 97% and 86%, respectively, compared to manual segmentation. Conclusions: In the current work we validated a fully-automated OCT segmentation algorithm, as well as a semiautomated variation of it in an extensive “real-life” dataset of OCT images. The study showed that our algorithm can perform rapid and reliable segmentation of OCT images

Adult Congenital Heart Disease Investigated with Cardiac Catheterization Over A 20-Year Period

BACKGROUND: Recent advances in diagnosis and treatment have increased the life expectancy of patients with congenital heart disease. METHODS: To investigate the prevalence of adult congenital heart disease (ACHD) in a large registry of patients over a 20-year period, we retrospectively assessed data of 14,012 males and 4,461 females who underwent clinically indicated cardiac catheterization from 1984 to 2003. RESULTS: ACHD was recorded in 234 subjects aged from 18 to 66 years, [95 males (40.7%) and 139 females (59.3%)]. Females were more likely to present with ACHD than males (p<0.001). Atrial septal defect was the most common defect (43.3%) followed by partial anomalous pulmonary venous return (12.0%), pulmonary valve stenosis (11.3%) ventricular septal defect (8.0%), coarctation of aorta (5.5%) patent ductus arteriosus (4.0%) and Fallot's tetralogy (3.3%). Atrial septal defect was more common in females (p<0.01), while pulmonary valve stenosis was more frequent in males (p<0.05). No difference across sexes was found in the other forms of ACHD. Females with ACHD were significantly older than males at the time of catheterization (median age 41 years, interquartile range 26 to 53 years vs. median age 35 years, interquartile range 22 to 48 years, p<0.05). CONCLUSIONS: In adulthood ACHD is found more commonly in females and is diagnosed later in life than in males. Atrial septal defect is the most prevalent form of ACHD and occurs most commonly in females

Influence of Oscillating Flow on LDL Transport and Wall Shear Stress in the Normal Aortic Arch

Lipid accumulation in the aortic wall is an important factor in the development of atherosclerosis. The Low Density Lipoprotein (LDL) at the surface of the endothelium in relation to Wall Shear Stress (WSS) in the normal human aortic arch under unsteady, normal flow and mass conditions was computationally analysed. Concave sides of the aortic arch exhibit, relatively to the convex ones, elevated LDL levels at the surface of the endothelium for all time steps. At the peak systolic velocity, the LDL level reaches a value 23.0% higher than that at entrance in the ascending-descending aorta region. The corresponding LDL levels at the surface of the endothelium for the near minimum entrance velocity instant reaches 26.0%. During the cardiac cycle, the highest area averaged normalized LDL taken up as compared to the lowest one is 0.69%. WSS plays an important role in the lipid accumulation. Low WSS regions are exposed to high LDL levels at the surface of the endothelium. Regions of elevated LDL levels do not necessarily co-locate to the sites of lowest WSS. The near wall paths of the velocities might be the most important factor for the elevated LDL levels at the surface of the endothelium

Accurate and reproducible reconstruction of coronary arteries and endothelial shear stress calculation using 3D OCT: Comparative study to 3D IVUS and 3D QCA

Background: Geometrically-correct 3D OCT is a new imaging modality with the potential to investigate the association of local hemodynamic microenvironment with OCT-derived high-risk features. We aimed to describe the methodology of 3D OCT and investigate the accuracy, inter- and intra-observer agreement of 3D OCT in reconstructing coronary arteries and calculating ESS, using 3D IVUS and 3D QCA as references. Methods-Results: 35 coronary artery segments derived from 30 patients were reconstructed in 3D space using 3D OCT. 3D OCT was validated against 3D IVUS and 3D QCA. The agreement in artery reconstruction among 3D OCT, 3D IVUS and 3D QCA was assessed in 3-mm-long subsegments using lumen morphometry and ESS parameters. The inter- and intra-observer agreement of 3D OCT, 3D IVUS and 3D QCA were assessed in a representative sample of 61 subsegments (n ¼ 5 arteries). The data processing times for each reconstruction methodology were also calculated. There was a very high agreement between 3D OCT vs. 3D IVUS and 3D OCT vs. 3D QCA in terms of total reconstructed artery length and volume, as well as in terms of segmental morphometric and ESS metrics with mean differences close to zero and narrow limits of agreement (BlandeAltman analysis). 3D OCT exhibited excellent inter- and intra-observer agreement. The analysis time with 3D OCT was significantly lower compared to 3D IVUS. Conclusions: Geometrically-correct 3D OCT is a feasible, accurate and reproducible 3D reconstruction technique that can perform reliable ESS calculations in coronary arteries

The prognostic value of dobutamine stress echocardiography amongst British Indian Asian and Afro-Caribbean patients: a comparison with European white patients

Background The incidence of cardiovascular disease is considerably disparate among different racial and ethnic populations. While dobutamine stress echocardiography (DSE) has been shown to be useful in Caucasian patients, its role among ethnic minority groups remains unclear. This study aimed to investigate the prognostic importance of DSE in three ethnic groups in the UK. Methods DSE was performed on 6231 consecutive patients. After exclusions, 5329 patients formed the study (2676 [50.2 %] Indian Asian, 2219 [41.6 %] European white and 434 [8.1 %] Afro-Caribbean). Study outcome measures were non-fatal cardiac events (NFCE) and all-cause mortality. Results There were 849 (15.9 %) NFCE and 1365 (25.6 %) deaths over a median follow-up period of 4.6 years. In total 1174 (22 %) patients had inducible myocardial ischaemia during DSE, 859 (16.1 %) had fixed wall motion abnormalities and 3645 (68.4 %) patients had a normal study. Ethnicity did not predict events. Among the three ethnic groups, ischaemia on DSE was associated with 2 to 2.5 times the risk of non-fatal cardiac events and 1.2 to 1.4 times the risk of all-cause mortality. Peak wall motion score index was the strongest independent predictor of non-fatal cardiac events and all-cause mortality in all groups. The C statistic for the prediction of NFCE and all-cause mortality were significantly higher when DSE parameters were added to the standard risk factors for all ethnic groups. Conclusions DSE is a strong predictor of NFCE and all-cause mortality and provides predictive information beyond that provided by standard risk factors in three major racial and ethnic groups. No major differences among racial and ethnic groups in the predictive value of DSE was detected