Rosaire Mongrain

Biocompatibility aspects of new stent technology

Stent implantation represents a major step forward since the introduction of coronary angioplasty. As indications continue to expand, better understanding of the early and late biocompatibility issues appears critical. Persisting challenges to the use of intracoronary stents include the prevention of early thrombus formation and late neointima development. Different metals and designs have been evaluated in animal models and subsequently in patients. Polymer coatings have been proposed to improve the biocompatibility of metallic stents or to serve as matrix for drug delivery and they are currently undergoing clinical studies. The promises of a biodegradable stent have not yet been fulfilled although encouraging results have recently been reported. Continuous low dose-rate brachytherapy combining the scaffolding effect of the stent with localized radiation therapy has witnessed the development and early clinical testing of radioactive stents. The combined efforts of basic scientists and clinicians will undoubtedly contribute to the improvement of stent biocompatibility in the future.

Simultaneous Determination of Aortic Valve Area by the Gorlin Formula and by Transesophageal Echocardiography Under Different Transvalvular Flow Conditions: Evidence That Anatomic Aortic Valve Area Does Not Change With Variations in Flow in Aortic Stenosis☆

OBJECTIVES The purpose of this study was to determine the impact of changes in flow on aortic valve area (AVA) as measured by the Gorlin formula and transesophageal echocardiographic (TEE) planimetry. BACKGROUND The meaning of flow-related changes in AVA calculations using the Gorlin formula in patients with aortic stenosis remains controversial. It has been suggested that flow dependence of the calculated area could be due to a true widening of the orifice as flow increases or to a disproportionate flow dependence of the formula itself. Alternatively, anatomic AVA can be measured by direct planimetry of the valve orifice with TEE. METHODS Simultaneous measurement of the planimetered and Gorlin valve area was performed intraoperatively under different hemodynamic conditions in 11 patients. Left ventricular and ascending aortic pressures were measured simultaneously after transventricular and aortic punctures. Changes in flow were induced by dobutamine infusion. Using multiplane TEE, AVA was planimetered at the level of the leaflet tips in the short-axis view. RESULTS Overall, cardiac output, stroke volume and transvalvular volume flow rate ranged from 2.5 to 7.3 liters/min, from 43 to 86 ml and from 102 to 306 ml/min, respectively. During dobutamine infusion, cardiac-output increased by 42% and mean aortic valve gradient by 54%. When minimal flow was compared with maximal flow, the Gorlin area varied from (mean +/- SD) 0.44 +/- 0.12 to 0.60 +/- 0.14 cm2 (p < 0.005). The mean change in Gorlin area under different flow rates was 36 +/- 32%. Despite these changes, there was no significant change in the planimetered area when minimal flow was compared with maximal flow. The mean difference in planimetered area under different flow rates was 0.002 +/- 0.01 cm2 (p = 0.86). CONCLUSIONS By simultaneous determination of Gorlin formula and TEE planimetry valve areas, we showed that acute changes in transvalvular volume flow substantially altered valve area calculated by the Gorlin formula but did not result in significant alterations of the anatomic valve area in aortic stenosis. These results suggest that the flow-related variation in the Gorlin AVA is due to a disproportionate flow dependence of the formula itself and not a true change in valve area.

Effects of diffusion coefficients and struts apposition using numerical simulations for drug eluting coronary stents.

In the context of drug eluting stent, we present two-dimensional numerical models of mass transport of the drug in the wall and in the lumen to study the effect of the drug diffusion coefficients in the three principal media (blood, vascular wall, and polymer coating treated as a three-compartment problem) and the impact of different strut apposition configurations (fully embedded, half embedded, and not embedded). The different conditions were analyzed in terms of their consequence on the drug concentration distribution in the arterial wall. We apply the concept of the therapeutic window to the targeted vascular wall region and derive simple metrics to assess the efficiency of the various stent configurations. Although most of the drug is dispersed in the lumen, variations in the blood flow rate within the physiological range of coronary blood flow and the diffusivity of the drug molecule in the blood were shown to have a negligible effect on the amount of drug in the wall. Our results reveal that the amount of drug cumulated in the wall depends essentially on the relative values of the diffusion coefficients in the polymer coating and in the wall. Concerning the strut apposition, it is shown that the fully embedded strut configuration would provide a better concentration distribution.

A Method for Matching the Refractive Index and Kinematic Viscosity of a Blood Analog for Flow Visualization in Hydraulic Cardiovascular Models

In this work, we propose a simple method to simultaneously match the refractive index and kinematic viscosity of a circulating blood analog in hydraulic models for optical flow measurement techniques (PIV, PMFV, LDA, and LIF). The method is based on the determination of the volumetric proportions and temperature at which two transparent miscible liquids should be mixed to reproduce the targeted fluid characteristics. The temperature dependence models are a linear relation for the refractive index and an Arrhenius relation for the dynamic viscosity of each liquid. Then the dynamic viscosity of the mixture is represented with a Grunberg-Nissan model of type 1. Experimental tests for acrylic and blood viscosity were found to be in very good agreement with the targeted values (measured refractive index of 1.486 and kinematic viscosity of 3.454 milli-m2/s with targeted values of 1.47 and 3.300 milli-m2/s).

Endothelial Cell Morphologic Response to Asymmetric Stenosis Hemodynamics: Effects of Spatial Wall Shear Stress Gradients

Endothelial cells are known to respond to hemodynamic forces. Their phenotype has been suggested to differ between atheroprone and atheroprotective regions of the vasculature, which are characterized by the local hemodynamic environment. Once an atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress. Endothelial cell response to wall shear stress may be linked to the stability of coronary plaques. Unfortunately, in vitro studies of the endothelial cell involvement in plaque stability have been limited by unrealistic and simplified geometries, which cannot reproduce accurately the hemodynamics created by a coronary stenosis. Hence, in an attempt to better replicate the spatial wall shear stress gradient patterns in an atherosclerotic region, a three dimensional asymmetric stenosis model was created. Human abdominal aortic endothelial cells were exposed to steady flow (Re=50, 100, and 200 and tau=4.5 dyn/cm(2), 9 dyn/cm(2), and 18 dyn/cm(2)) in idealized 50% asymmetric stenosis and straight/tubular in vitro models. Local morphological changes that occur due to magnitude, duration, and spatial gradients were quantified to identify differences in cell response. In the one dimensional flow regions, where flow is fully developed and uniform wall shear stress is observed, cells aligned in flow direction and had a spindlelike shape when compared with static controls. Morphological changes were progressive and a function of time and magnitude in these regions. Cells were more randomly oriented and had a more cobblestone shape in regions of spatial wall shear stress gradients. These regions were present, both proximal and distal, at the stenosis and on the wall opposite to the stenosis. The response of endothelial cells to spatial wall shear stress gradients both in regions of acceleration and deceleration and without flow recirculation has not been previously reported. This study shows the dependence of endothelial cell morphology on spatial wall shear stress gradients and demonstrates that care must be taken to account for altered phenotype due to geometric features. These results may help explain plaque stability, as cells in shoulder regions near an atherosclerotic plaque had a cobblestone morphology indicating that they may be more permeable to subendothelial transport and express prothrombotic factors, which would increase the risk of atherothrombosis.

Incidence of Stent Under-Deployment as a Cause of in-Stent Restenosis in Long Stents

Although stent under-deployment (SU) has been associated with increased risk of in-stent restenosis, little data have been reported on the incidence of SU in patients presenting with clinical in-stent restenosis. In 59 patients referred for vascular brachytherapy and showing angiographic in-stent restenosis, we sought (1) to determine the incidence of SU using standard intravascular ultrasound (IVUS) criteria (2) to evaluate the effects of repeat angioplasty on further stent expansion. Stented length was 32 ± 17 mm and diameter stenosis was 75 ± 14%. Before re-intervention, the incidence of reduced absolute values of minimal stent cross-sectional area (MSCSA) varied from 69%(≤8 mm2) to 15%(≤5 mm2). After re-intervention, the incidence decreased to 24%(≤8 mm2)(p= 0.0001) and 0%(≤5 mm2)(p= 0.005). Before re-intervention, SU as assessed by relative criteria varied from 21%(80% mean reference lumen area or 90% minimum distal reference lumen area) to 28%(100% minimum reference lumen area). After re-intervention, the incidence of SU varied from 7%(90% minimum distal reference lumen area)(p= 0.0001 vs. pre) to 24%(55% mean reference EEM area)(p= ns). No change in strut apposition (97% pre vs. 100% post) nor in symmetry index (100% pre vs. post) was noted. From all criteria, the 90 and 100% minimum reference lumen area criteria were the most altered by repeat balloon dilatation, 21% pre vs. 7% post and 28% pre vs. 11% post, respectively. In conclusion, among patients presenting with severe angiographic in-stent restenosis, a significant number showed signs of SU whose incidence varied according to applied criteria. Significant stent re-expansion can be obtained following IVUS-guided repeat angioplasty irrespective of initial SU criteria.

Accurate Prediction of Wall Shear Stress in a Stented Artery: Newtonian Versus Non-Newtonian Models

A significant amount of evidence linking wall shear stress to neointimal hyperplasia has been reported in the literature. As a result, numerical and experimental models have been created to study the influence of stent design on wall shear stress. Traditionally, blood has been assumed to behave as a Newtonian fluid, but recently that assumption has been challenged. The use of a linear model; however, can reduce computational cost, and allow the use of Newtonian fluids (e.g., glycerine and water) instead of a blood analog fluid in an experimental setup. Therefore, it is of interest whether a linear model can be used to accurately predict the wall shear stress caused by a non-Newtonian fluid such as blood within a stented arterial segment. The present work compares the resulting wall shear stress obtained using two linear and one nonlinear model under the same flow waveform. All numerical models are fully three-dimensional, transient, and incorporate a realistic stent geometry. It is shown that traditional linear models (based on bloods lowest viscosity limit, 3.5 Pa s) underestimate the wall shear stress within a stented arterial segment, which can lead to an overestimation of the risk of restenosis. The second linear model, which uses a characteristic viscosity (based on an average strain rate, 4.7 Pa s), results in higher wall shear stress levels, but which are still substantially below those of the nonlinear model. It is therefore shown that nonlinear models result in more accurate predictions of wall shear stress within a stented arterial segment.

Development of coronary aneurysm after cutting balloon angioplasty: Assessment by intracoronary ultrasound

We report the case of a coronary aneurysm observed 6 mo after cutting balloon angioplasty complicated by a mild perforation. Intravascular ultrasound allowed characterization of the malformation as a true aneurysm. The clinical course was uneventful.

Reliability of mechanical and phased-array designs for serial intravascular ultrasound examinations

Background: Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials. Methods: We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients. Results: Both systems correlated well for areas (r ≥ 0.90, p < 0.0001) and diameters (r ≥ 0.84, p < 0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: −0.24 and 0.96 mm2, p < 0.055) and diameter (−0.08 and 0.16 mm, p < 0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (r ≥ 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small. Conclusions: Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials.

Forward and Inverse Problems in Endovascular Elastography

This paper is about Endo Vascular Elastography (EVE), a new technique for the diagnostic of arterial disease which gives information about plaque mechanical properties. Given this, EVE can provide useful information that could guide therapeutic decisions. Two important problems are considered: a) the Forward Problem (FP) of predicting the strain field of a tissue with a known elasticity and subjected to a known surface traction applied as a boundary condition, and b) the Inverse Problem (IP) of reconstructing the elasticity distribution from the measured displacement field, the boundary conditions and the governing equations. In the FP, arterial elastic properties are disclosed in the tissue displacement induced by a small intraluminal pressure change; the pre- and post- compression ultrasound signals are used to estimate radial (axial) tissue displacement and the corresponding strain. The approach we adopted to solve the IP consists in minimizing the least squares error between observed and predicted displacement fields. It uses an iterative procedure where at each iteration a linear inversion scheme based on a perturbation method is implemented. The paper illustrates the FP and IP implementation we have realized.