Are intramural suction-squeezing effects generated by the variations in radial wall stress during each heart beat the motor of atherosclerosis? A new concept.

In the early sixties, the existence of predilection sites for atherosclerotic lesions inside the arterial circulation led to the concept that low wall shear stress (WSS) was responsible, together with systemic factors like high blood pressure, hypercholesterolemia, or diabetes, for the genesis and progression of atherosclerosis. It was found later that oscillating WSS and high WSS gradients could also be incriminated. Yet, this concept, which is broadly accepted today, fails to explains several facts, for instance that some arteries (e.g. epicardial coronary arteries) are more prone to become atherosclerotic than other ones exposed to the same systemic factors (e.g. hepatic and brain arteries). In this paper, we present a quite different concept. It is based on the fact that the increase in intravascular pressure and flow that occur in the arteries during systole generates, at the predilection sites of atherosclerotic lesions (bends, bifurcations, and branchings), an increase of radial wall stress in the outer layers of the arterial wall so that this stress becomes momentarily tensile. These cyclic stress increases have a suction effect that is likely to facilitate the diffusion of atherogenic cells and substances inside the wall. Furthermore, since arteries are not primarily structured to resist inversions of radial stress, they may also create damages (e.g. disruptions of cell membranes and elastic lamellae) followed by inflammations and micro-haemorrhages in the wall. This new concept may provide a complementary (or possibly alternative) explanation of atherosclerosis.

An analytical model for the investigation of axial wall forces generated by an arterial stenosis.

The causes of arteriosclerosis are intensively investigated since many decades. While circumferential wall stress has received a lot of attention, axial stress (also called "longitudinal" stress) has been largely neglected, and practically never incriminated. However, it has been suggested in 2003 that moderate and severe arterial stenoses may induce non negligible axial forces cyclically in the vessel segment just proximal to the constriction cone. In the present contribution, we describe a simple analytical model that allows to study the distribution of these forces along the vessel in dependence of the respective axial elasticities of vessel and surrounding tissues, and of the stenosis length.

[Acute myocardial infarction due to spontaneous coronary artery dissection]. / Infarctus aigu du myocarde secondaire a une dissection coronaire spontanée. A propos de 6 cas.

BACKGROUND: Spontaneous coronary dissection is a rare cause of acute myocardial infarction (AMI). Its aetiology and treatment have not yet been well defined. In this report, we review the clinical presentation, the aetiology, the risk factors and the treatment of 6 cases of AMI due to spontaneous coronary dissection. METHODOLOGY AND RESULTS: We have reviewed 1100 cases of AMI having undergone coronary angiography in our institution during the period December 1999 to January 2004. Six cases (0.5%; 5 men, mean age: 38 years) in which spontaneous coronary dissection had been retained as final aetiology were further analyzed. Four patients had no cardiovascular risk factors but, interestingly, in all 6 patients we found a clear triggering factor of the acute event: extreme physical stress (5), or psychological stress (1). Thrombolysis had been performed in 5 patients, and the coronary angiography carried out thereafter showed a dissection of the left anterior descending coronary (2 cases), of the right coronary artery (3 cases) or of the left circumflex artery (1 case). All patients had a preserved coronary flow (TIMI 3). On the basis of the angiographical findings, medical treatment (4 patients), coronary artery by-pass grafting (1 patient), or percutaneous angioplasty with stenting (1 patient) were performed. The only major cardiac adverse event observed in the early follow up was a sudden acute thrombosis of the coronary stent. CONCLUSION: In young patients without cardiovascular risk factors and presenting with AMI subsequent to a physical or emotional stress, spontaneous coronary artery dissection should imperatively be taken into consideration as a possible diagnosis. Since intravenous thrombolysis may worsen the dissection, we recommend primary emergency coronarography as a diagnostic and (sometimes) therapeutic treatment option.

Estimation of the axial wall strains induced by an arterial stenosis at peak flow.

In the last 30 years, thousands of basic or clinical studies have been devoted to atherosclerosis or to the problem of restenosis after angioplasty. In these studies, axial stresses in the vessel wall have received practically no attention, contrary to circumferential stress and purely biological aspects. Based on a recent article describing how arterial stenoses can induce a considerable increase in axial wall stress during flow systole in the region immediately proximal to the stenosis entrance, we have used a simple (theoretical) spring model and data available in the literature on the mechanical properties of arteries to investigate the relative wall elongations (axial strains) resulting from the systolic increases in axial stress generated by the stenosis. The model shows that high axial wall strains are tightly limited to the stenosis entrance if the axial wall forces generating the supplementary stress are strongly absorbed by the tissues surrounding the vessel. Inversely, if this absorption is weak, the zone of high strains extends over a longer vessel segment upstream of the stenosis entrance. The maximum strain value, which is always situated at the stenosis entrance, appears to be relatively independent of the presence or absence of surrounding tissues. The simulation also shows that in a 3 mm coronary artery presenting a 75% diameter stenosis, the axial strain at the stenosis entrance can exceed 10% at peak flow, depending on the respective axial elasticities of vessel wall and surrounding tissues. In a more severe stenosis, or in case of a pathologically high systolic pressure, the maximum strain value might even exceed 20%. Since abnormal axial strains have been shown to induce abnormal biological processes in smooth muscle cells cultures, it is quite conceivable that such axial strains are deleterious, at least in arterial segments whose length normally does not vary.

[Comparative study of left ventricular ejection fraction and volume by 2 isotopic methods and contrast angiography]. / Etude comparative des fractions d'éjection et volumes ventriculaires gauches obtenus par deux méthodes isotopiques et par l'angiographie de contraste.

The tomographic mode has replaced the planar mode for radióisotopic studies of myocardial perfusion but not for the study of systolic ventricular function. The aim of this study was to compare monophotonic emission tomography (MPET), the planar mode (PM) and contrast angiography (Angio). The left ventricular volumes and ejection fractions were measured in 111 patients by the tomographic and planar modes and by biplane angiography in 70 of them. The MPET algorithm (QBS software) identified the ventricular endocardium in 96 of the 111 procedures (86%). The mean left ventricular ejection fractions (LVEF) were 57 +/- 17% (MPET, N = 96), 55 +/- 15% (PL, N = 96) and 57 +/- 15% (Angio, N = 70). There was a good correlation of LVEF between MPET and PL and MPET and Angio with negligible bias of 3 +/- 6% and 2 +/- 4% respectively and high correlation coefficients, r = 0.94 (MPET = 1.05*PL-0.2) and r = 0.93 (MPET = 1.1 x Angio-3). The differences between the 95% confidence intervals between MPET and PL and MPET and Angio may be explained by an overestimation of normal LVEF by MPET, especially in patients with low end systolic volumes. In these cases, the difference in LVEF by MEPT and the average LVEF from the 3 techniques was greater: 6 +/- 4% (< or = 20 ml) vs 0 +/- 3% (> 20 ml) (p < 0.0001). The authors conclude that, with the reserve that a high percentage of investigations could not be analysable. MPET seems to be a method of choice for assessing left ventricular systolic function.

A morphological-mechanical explanation of edge restenosis in lesions treated with vascular brachytherapy.

PURPOSE: Edge restenosis in stenotic lesions treated by implantation of a conventional stent followed (or preceded) by a catheter-based brachytherapy is often attributed to "geographic miss" (GM). We propose a complementary (or, possibly, alternative) explanation based on the concept that a clear postprocedural mismatch between the in-stent lumen and the normal (undilated) lumens of the proximal and/or distal vessel segments results in an excessive, damageable increase of axial wall stress in these segments. METHODS: The possible poststenting situations at both margins of a stent are examined, and based on the presence or absence of an increase in axial wall stress, predictions are made about the lesion evolution. The concept is then also examined in the light of published observations. RESULTS: None of the analyzed observations appeared to be incompatible with the proposed morphological-mechanical explanation. CONCLUSION: From a mechanical point of view, optimal matching of the proximal and distal stent diameters to the corresponding normal diameters of the adjacent arterial segment is likely to reduce the rate of edge restenosis.

Is axial wall stress compressive in certain arteries?

In mathematical-physical models of blood vessels, the "zero-stress state" of the vessel wall is usually defined with reference to the atmospheric pressure (pa approximately 750 mmHg = 100 kPa). Due to this conventional choice, axial and circumferential stresses generated by the (positive) transmural pressure over the radial wall depth can only be positive (in absence of residual stresses) and thus, by definition, only tensile. If the zero-stress state were defined "unconventionally" with reference to vacuum pressure (= 0 mm Hg), the isotropic compressive stress--pa generated by the atmospheric pressure everywhere in the wall would, however, be included in the stress values, and negative (= compressive) stresses would become formally possible. Since materials submitted only to compressions do not need to have the same resistive properties as materials which may also experience tractions, the question whether axial stress (and perhaps also circumferential stress) might be permanently compressive in vessels under physiologic conditions may therefore be important for investigations of the relationship between wall stresses on one side and wall structures, vessel growth, vessel damages, or vessel adaptation processes on the other side. In the present study, radial, circumferential, and axial wall stresses were calculated conventionally and "unconventionally" for three representative "vessel examples." The results clearly suggest that axial wall stress might well be compressive in many vessels. Furthermore, relative differences between conventional and unconventional stress values are quite considerable, and ratios between stresses calculated in the same manner appear to be strongly dependent on the chosen zero-stress state definition.

The effect of image distortion on 3-D reconstruction of coronary bypass grafts from angiographic views.

Three-dimensional (3-D) reconstructions of coronary bypass grafts performed from X-ray angiographic images may become increasingly important for the investigation of damaging mechanical stresses imposed to these vessels by the cyclic movement of the heart. Contrary to what we had experienced with coronary arteries, appreciable reconstruction artifacts frequently occur with grafts. In order to verify the hypothesis that those are caused by distortions present in the angiographic images (acquired with image intensifiers), we have implemented a grid correction technique in our 3-D reconstruction method and studied its efficiency with phantom experiments. In this article, the nature of the encountered artifacts and the way in which the dewarping correction eliminates them are illustrated by a phantom experiment and by the reconstruction of a real coronary bypass vein graft.

In-vivo measurements of wall shear stress in human coronary arteries.

BACKGROUND: Wall shear stress (WSS) is closely associated with arteriosclerosis. WSS values for various vessels and species are available, but fully in-vivo measurements in human coronary arteries have not yet been reported. OBJECTIVE: To measure WSS in undiseased coronary arteries of adult patients at rest. METHODS: We recorded the temporal average value (APV) of the instantaneous maximal blood velocity in the three vessel segments of angiographically normal coronary artery bifurcations in 21 patients undergoing cardiac catheterization to treat various diseases by means of a 0.036 cm Doppler wire (FloWire). In total, 36 bifurcations were examined. The 36 x 3 cross-sectional areas (CSA) were determined by means of a three-dimensional angiographic technique. The three flows, Q1 (inflow), Q2, and Q3 of each bifurcation were calculated according to Q=0.5 x APV x CSA. For each segment, WSS was calculated as WSS=32 eta Q/(pi D3) (where blood viscosity eta=3.5 mPa s and D is vessel diameter). Only the 54 WSS values obtained from the 18 flow triplets which satisfied the equation Q1/(Q2+Q3)=1 better than did the 18 other ones were retained. RESULTS: The 54 WSS values ranged from 0.33 to 1.24 Pa (mean 0.68 Pa, SEM, 0.027 Pa). They did not depend significantly on Q (r=0.07; P=0.60) and the CSA (r=0.24, P=0.08) but the second relationship approached significance. CONCLUSION: The obtained mean WSS value (0.68 Pa) is half the value predicted for coronary arteries from optimality principles. It is also smaller than many values reported for human carotid, renal, and femoral arteries.

X-ray dose to the skin in patients undergoing percutaneous transluminal coronary angioplasty.

Dose measurements were performed with an ionization chamber placed on the surface of a polystyrene phantom to estimate the radiation dose to the skin from fluoroscopy in patients undergoing PTCA and to define parameters predicting for high-risk irradiation conditions. Dose rate changes were analyzed as a function of phantom thickness, X-ray source-to-phantom distance, image intensifier-to-phantom distance, and field size. Skin dose calculations were made in 38 PTCA patients to validate the model. Thickness was the most important factor determining dose rate changes in the phantom's surface. Dose rate increased by a factor of almost 4 with each 10-cm increment in thickness, doubled upon decreasing the field diameter from 17 cm to 14 cm, and increased by a factor of 1.2 to 1.8 upon decreasing the source-to-phantom distance or by increasing the image intensifier-to-patient distance. All these parameters may significantly increase the dose to the skin and augment the risk for skin injuries post-PTCA.

Accuracy of coronary flow measurements performed by means of Doppler wires.

To estimate in patients the accuracy of coronary flow measurements performed by means of 0.014" Doppler wires, the time-averaged maximal blood velocity (APV) was recorded in the 3 branches of 36 angiographically normal coronary artery bifurcations selected in 21 patients undergoing cardiac catheterization for various diseases. Contrast medium injections filmed under two incidences allowed identification of the 3 sample volume locations and computing of the 3 corresponding vessel cross-sectional areas (CSA) at subsequent data analysis. Multiplication of the velocities APV/2 (range: 3 to 20.5 cm/s) by the CSA (obtained by averaging the two calibrated vessel diameters; range: 1.6 to 5.4 mm) yielded 108 flow rates (range: 5.4 to 169 mL/min). The average relative flow error was then estimated using the continuity equation (Q(in) = Q(out,1) + Q(out, 2)) and the central limit theorem. The result was that the relative flow error decreased from 30% at Q = 30 mL/min to 13% at Q = 160 mL/min. We conclude that coronary flow measurements are reasonably accurate, except perhaps for very low flows.

A new technique for improved densitometric quantification of coronary artery stenoses in angiographic images.

In vitro studies have demonstrated that densitometric quantification of coronary artery stenoses is superior to geometric methods to assess non-circular lumens. However, in patients, several authors have reported significant discrepancies between area reduction percentages obtained densitometrically from two different imaging projections. Some of the factors causing the discrepancies can be reduced by simple precautions taken during image acquisition. Some others may be compensated for during analysis. Nevertheless, two factors remain problematic. The first is the inadequate spatial orientation of the vessel axes at the stenotic and reference cross sections with respect to the x-rays. The second is the difficulty in identifying the same vessel cross section in both planes at the time of analysis. We have designed a new densitometric technique that eliminates the error contributions of these two factors. The technique requires simultaneously acquired biplane coronary angiograms and biplane images of a translucent cube bearing steel markers acquired in exactly the same biplane geometry. Using the two projection matrices calculated from the images of the cube, the centerlines and the edges of the coronary arteries can be reconstructed in space from the biplane angiograms. The angles between the vessel axes and the x-ray beams can be determined and the densitometric cross sections can be corrected accordingly. Moreover, the 3D reconstruction allows the identification of the same cross section in the two planes for the determination of the area reduction percentages. Validation measurements were performed on a Perspex phantom and in patients, before and after angioplasty. In both types of measurement, the interplane discrepancies could be roughly halved. The densitometric technique presented can be incorporated into routine angiography and could become a strong alternative to the geometric approach that is presently dominating this field.

A new densitometric approach to the assessment of mean coronary flow.

RATIONALE AND OBJECTIVES: The authors present an angiographic method to measure absolute coronary blood flow in patients. METHODS: The left or right coronary tree is three-dimensional (3D)-reconstructed from biplane coronary angiograms. This allows the determination of the intravascular volumes needed for flow measurement. The 3D distance traveled by the contrast medium during one cardiac cycle is determined by appropriately thresholding the "concentration-distance", curves computed on two pairs of images taken one cardiac cycle apart. RESULTS: The angiographic flow measurements were compared with nearly simultaneous flow determinations obtained with an intracoronary ultrasonic Doppler flow velocity measuring device. The mean relative difference between the Doppler and the 3D measurements was 11% and the two sets of flow values correlated well (r = 0.81). CONCLUSIONS: A method for the determination of mean coronary flow is presented. The procedure is simple and can be incorporated easily into clinical routine.

Towards a gold standard for quantitative coronary arteriography.

Densitometric quantification of coronary artery stenoses in angiographic images can be problematic for two reasons: (i) the x-rays are inadequately oriented with respect to the vessel segments of interest at image acquisition; (ii) non-linear effects due for instance to beam hardening, scattered radiation and veiling glare may reduce the accuracy. As a consequence, appreciable discrepancies between degrees of stenosis measured in two different projections can occur. To overcome these limitations, we have designed and tested a combined correction that compensates (at subsequent analysis) for the error contributions due to the cited sources. It implies 3D reconstruction of the vessel segments of interest and consequently requires an appropriate biplane coronary angiogram. In experiments performed with a dedicated phantom, application of the correction improved the correlation between measured and true area reduction percentages (without correction: y = 1.04x - 4%, r = 0.97, SEE = 6%, n = 35; with correction: y = 1.02x - 0%, r = 0.99, SEE = 3%, n = 35). Applied to ten area stenoses measured biplane in patients and exhibiting strong interplane discrepancies, the correction had a comparable effect (without correction: y = 0.83x - 11%, r = 0.86, SEE = 9%, n = 10; with correction: y = 0.83x + 2%, r = 0.98, SEE = 4%, n = 10). The new densitometric method could possibly be used as a gold standard in the objective evaluation of geometric methods in patients.

Is the indicator dilution theory really the adequate base of many blood flow measurement techniques?

The indicator dilution theory is the underlying model of many blood flow measurement techniques used daily in hospitals, for instance in cardiac catheterization laboratories. The basic version of this theory applies to a "stationary" flow system with one inlet and one outlet, into which a small amount M of indicator is injected "suddenly" at time t = 0 at the inlet. The quintessence of the theory consists in three equations, which themselves result from some apparently simple assumptions about the considered flow systems. The first equation states that the (constant) flow Q through the system can be calculated by use of the known amount of indicator, M, and of the indicator concentration-time curve c(t) recorded at the outlet. The second one allows the calculation of the "mean transit time" t* of fluid and indicator particles through the system from the curve c(t). The third equation, V = Qt*, yields the system volume V. It is generally believed that these three equations would be absolutely valid if the assumptions of the theory could be perfectly fulfilled. We show, by considering a simple model, that all three equations are actually incorrect for most flow systems when the detector used to record the curve c(t) is of the "trans-illumination" type, as is the case for instance in dye dilution methods and in many angiographic or CT techniques. A further consequence is that t*, which is truly the "center of mass" of the concentration-time curve c(t), does not have the well known property of being the adequate parameter for flow determinations. Many flow measurement techniques thus appear to have no theoretical base.

The impact of vessel orientation in space on densitometric measurements of cross sectional areas of coronary arteries.

Under ideal conditions, densitometric measurement of a coronary arterial cross section in biplane angiographic images should result in nearly equal cross sectional areas for both planes. However, quite appreciable discrepancies have been found by some authors in patients. In this study, the role of inadequate spatial orientation of the vessel axes relatively to the x-rays was assessed by use of a 3D technique applied to 60 stenoses (45 pre PTCA and 15 post PTCA) in simultaneously acquired digital biplane coronary angiograms of 27 CAD patients. The 3D technique yields two radius values per projection directly in mm at any arterial cross section of interest. This was used to determine the areas Ar(in mm2) of the reference cross sections. As with catheter calibration, these cross sections were thus assumed to be more or less circular, but out-of-plane effects and errors due to a catheter diameter determination in pixels were avoided. The areas of the stenotic sections were then determined densitometrically (in mm2) from the two projections (1 and 2) according to As1 = ArDs1/Dr1, resp. As2 = ArDs2/Dr2, where Dr1, Dr2, Ds1 and Ds2 are the conventional densitometric areas of the reference and stenotic cross sections measured in planes 1 and 2. As expected, the areas As1 and As2 correlated only moderately: As2 = 0.92 As1 + 0.7 mm2, r = 0.82, n = 60, SEE = 1.4 mm2. The 3D method also yielded the two spatial angles between the local vessel axis and the X-rays of both planes. These two angles were then used to correct each densitometric area for inadequate orientation. With the corrected densitometric areas As1c and As2c, the correlation improved to: As2c = 1.05 As1c + 0.03 mm2, r = 0.93, n = 60, SEE = 0.8 mm2. Inadequate orientation of the cross sections in space thus appears to be an important factor of inaccuracy in densitometric measurements of stenotic cross sections in patients.

Applying the object paradigm to a centralized database for a cardiology division.

In order to master the overwhelming quantity of data produced by the different laboratories of our Cardiology Division, we are presently developing a centralized database. Our aim is to improve the quality of diagnoses and therapies by constituting patient centered medical files integrating logically the results of the results of the different examinations and allowing for a rapid access to the patient data. The database has to be accessible from an heterogeneous set of PC, MacIntoshes and UNIX workstations. It must have an ergonomic graphic user interface and generate reports which can be sent to the patient physician. It is well known that the requirements for a medical database make its conceptual analysis very difficult. As medical knowledge continually evolves, the examination protocols change and, therefore, the data sets have to be updated. The maintenance of classical databases is usually expensive because it requires specialized staff to alter the database structure and to adapt the user interface. To allow for flexibility, modularity, code reusability and reliability, the object paradigm was applied to a classical relational database. Thanks to the combination of both data structure and behavior in single entities, it is possible to build generic user interfaces which can be easily tailored to the needs of every laboratory of our Cardiology Division.

Computer simulation of the propagation of contrast medium in a coronary artery during one cardiac cycle.

In some angiographic methods for measurement of mean coronary flow in ml/min, a threshold is applied to 'concentration-distance' curves obtained from a constant rate injection by computing the intravascular contrast medium concentration along the main coronary branches. If the shape of the velocity profile would remain parabolic throughout the cardiac cycle, the correct threshold value would be '50% of the concentration at the injection site'. But, coronary flow being strongly pulsatile, the shape of the velocity profile must be expected to vary appreciably within the cardiac phase. In order to investigate if a single, appropriate threshold value nevertheless exists for a great variety of coronary flow pulses and velocity profiles, the spreading of contrast medium injected continuously in a tube perfused by a time varying flow Q(t) was studied by computer simulation. While the particular time courses of flow and velocity profile appear to be of secondary importance, the ratio 'injection rate to peak coronary flow' has a major impact. If it is equal to or greater than 1, a threshold value of 47% is the best choice. If the ratio is markedly less than 1, no appropriate threshold exists and use of the 47% threshold will result in considerable flow underestimations. This was fully confirmed by measurements of absolute coronary flow performed in patients.

Quantification of intracoronary volume by videodensitometry: validation study using fluid filling of human coronary casts.

Changes in intracoronary volume reflect the hemodynamic significance of progression or regression of diffuse coronary artery disease where intracoronary catheters cannot be applied for direct measurements due to small vessel dimensions. We have validated the videodensitometric measurement of intracoronary volume with epoxy casts of postmortem human coronary arteries. The volume of 31 coronary segments (cross-sectional areas in a range of 2-13 mm2) measured by fluid-filling using a precision dispenser was compared with the respective single plane intracoronary volume assessments obtained by the videodensitometric algorithm of the new generation Cardiovascular Angiography Analysis System (CAAS II). The true and measured values of volume were compared by calculation of the mean of the signed differences +/- standard deviation and by linear regression analysis. Videodensitometric measurement of intracoronary volume correlate well with fluid-filling of human coronary artery casts (correlation coefficient: r = 0.99, y = 1.96 +/- 0.99x, standard error of estimate: SEE = 3.96) with a significant trend towards overestimation of true volume values (mean difference = 1.73 +/- 3.64 mm3, P < 0.05). Intracoronary volume estimations can be used to measure changes of luminal dimensions of coronary arteries and may offer a new approach to assessment of progression or regression of diffuse coronary artery disease.