High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques.

BACKGROUND AND AIMS: Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons. METHODS: Participants (n = 74) from the population-based Rotterdam Study, all with carotid atherosclerosis assessed on ultrasound, underwent carotid MRI. Multiple MRI sequences were used to evaluate the presence of IPH, LRNC and/or calcifications in plaques in the carotid arteries. Images were automatically segmented for lumen and outer wall to obtain a 3D reconstruction of the carotid bifurcation. These reconstructions were used to calculate minimum, mean and maximum shear stresses by applying computational fluid dynamics with subject-specific inflow conditions. Associations between shear stress measures and plaque composition were studied using generalized estimating equations analysis, adjusting for age, sex and carotid wall thickness. RESULTS: The study group consisted of 93 atherosclerotic carotid arteries of 74 participants. In plaques with higher maximum shear stresses, IPH was more often present (OR per unit increase in maximum shear stress (log transformed) = 12.14; p = 0.001). Higher maximum shear stress was also significantly associated with the presence of calcifications (OR = 4.28; p = 0.015). CONCLUSIONS: Higher maximum shear stress is associated with intraplaque haemorrhage and calcifications.

The role of shear stress in the generation of rupture-prone vulnerable plaques.

Blood-flow-induced shear stress acting on the arterial wall is of paramount importance in vascular biology. Endothelial cells sense shear stress and largely control its value in a feedback-control loop by adapting the arterial dimensions to blood flow. Nevertheless, to allow for variations in arterial geometry, such as bifurcations, shear stress control is modified at certain eccentrically located sites to let it remain at near-zero levels. In the presence of risk factors for atherosclerosis, low shear stress contributes to local endothelial dysfunction and eccentric plaque build up, but normal-to-high shear stress is atheroprotective. Initially, lumen narrowing is prevented by outward vessel remodeling. Maintenance of a normal lumen and, by consequence, a normal shear stress distribution, however, prolongs local unfavorable low shear stress conditions and aggravates eccentric plaque growth. While undergoing such growth, eccentric plaques at preserved lumen locations experience increased tensile stress at their shoulders making them prone to fissuring and thrombosis. Consequent loss of the plaque-free wall by coverage with thrombus and new tissue may bring shear-stress-controlled lumen preservation to an end. This change causes shear stress to increase, which as a new condition may transform the lesion into a rupture-prone vulnerable plaque. We present a discussion of the role of shear stress, in setting the stage for the generation of rupture-prone, vulnerable plaques, and how this may be prevented.

Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition.

BACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown. METHODS AND RESULTS: PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and -49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up. CONCLUSIONS: Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.

Relationship between neointimal thickness and shear stress after Wallstent implantation in human coronary arteries.

BACKGROUND: In-stent restenosis by excessive intimal hyperplasia reduces the long-term clinical efficacy of coronary stents. Because shear stress (SS) is related to plaque growth in atherosclerosis, we investigated whether variations in SS distribution are related to variations in neointima formation. METHODS AND RESULTS: In 14 patients, at 6-month follow-up after coronary Wallstent implantation, 3D stent and vessel reconstruction was performed with a combined angiographic and intravascular ultrasound technique (ANGUS). The bare stent reconstruction was used to calculate in-stent SS at implantation, applying computational fluid dynamics. The flow was selected to deliver an average SS of 1.5 N/m(2). SS and neointimal thickness (Th) values were obtained with a resolution of 90 degrees in the circumferential and 2.5 mm in the longitudinal direction. For each vessel, the relationship between Th and SS was obtained by linear regression analysis. Averaging the individual slopes and intercepts of the regression lines summarized the overall relationship. Average Th was 0.44+/-0.20 mm. Th was inversely related to SS: Th=(0.59+/-0.24)-(0.08+/-0.10)xSS (mm) (P<0.05). CONCLUSIONS: These data show for the first time in vivo that the Th variations in Wallstents at 6-month follow-up are inversely related to the relative SS distribution. These findings support a hemodynamic mechanism underlying in-stent neointimal hyperplasia formation.

True 3-dimensional reconstruction of coronary arteries in patients by fusion of angiography and IVUS (ANGUS) and its quantitative validation.

BACKGROUND: True 3D reconstruction of coronary arteries in patients based on intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS information (ANGUS). The clinical applicability of ANGUS was tested, and its accuracy was evaluated quantitatively. METHODS AND REUSLTS: In 16 patients who were investigated 6 months after stent implantation, a sheath-based catheter was used to acquire IVUS images during an R-wave-triggered, motorized stepped pullback. First, a single set of end-diastolic biplane angiographic images documented the 3D location of the catheter at the beginning of pullback. From this set, the 3D pullback trajectory was predicted. Second, contours of the lumen or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular rotation of the reconstruction was optimized by quantitative matching of the silhouettes of the 3D reconstruction with the actual biplane images. Reconstructions were obtained in 12 patients. The number of pullback steps, which determines the pullback length, closely agreed with the reconstructed path length (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions showed high correlation (0.84 to 0.97) with corresponding measurements in the actual biplane angiographic images. CONCLUSIONS: With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.

On the IVUS plaque volume error in coronary arteries when neglecting curvature.

Plaque volume determined by common linear 3-D IVUS analysis systems will show under- or overestimation in curved vessel segments because these systems approximate the true 3-D transducer pull-back trajectory by a straight line. We developed a mathematical model that showed that the error is primarily dependent on the curvature of the pull-back trajectory and not on vessel tortuosity. Furthermore, we measured this error in vivo in the coronary arteries of 15 patients, comparing the plaque volume using a true 3-D reconstruction method with that of the linear approach. The in vivo plaque volume error ranged from 2.3% to -1.2% for 15 coronary segments with lengths ranging from 38.8 to 89.1 mm (62.2 +/- 13 mm). The volume error introduced by linear 3-D IVUS analysis systems is dependent on the curvature of the pull-back trajectory. The error measured in vivo was small and inversely related to segment length.

Shear stress in atherosclerosis, and vascular remodelling.

Shear stress plays a role in lipid accumulation in primary atherosclerosis and vascular remodelling. We will present applications of a new technique, which enables to quantify shear stress in 3D vessel reconstructions. The method is based on 3D IVUS reconstructions of blood vessels either obtained by IVUS pull back (external iliac artery) or by a combination of angiography and IVUS (curved coronary artery). Distribution of wall thickness of a curved human right coronary artery was such that low wall thickness occurred where shear stress was high, and wall thickness was high where shear stress was low. Consequently, an inverse relationship between shear stress and wall thickness was detected. Although vascular remodelling after PTA in external iliac arteries of atherosclerotic Yucatan pigs was predicted both by acute gain and decrements in shear stress, the decrement in shear stress appeared a better predictor. In conclusion, shear stress appears to play a role in primary atherosclerosis and vascular remodelling after PTA.

Evaluation of endothelial shear stress and 3D geometry as factors determining the development of atherosclerosis and remodeling in human coronary arteries in vivo. Combining 3D reconstruction from angiography and IVUS (ANGUS) with computational fluid dynamics.

The predilection sites of atherosclerotic plaques implicate rheologic factors like shear stress underlying the genesis of atherosclerosis. Presently no technique is available that enables one to provide 3D shear stress data in human coronary arteries in vivo. In this study, we describe a novel technique that uses a recently developed 3D reconstruction technique to calculate shear stress on the endothelium with computational fluid dynamics. In addition, we calculated local wall thickness, the principal plane of curvature, and the location of plaque with reference to this plane, relating these results to shear stress in a human right coronary artery in vivo. Wall thickness and shear stress values for the entire vessel for three inflow-velocity values (10 cm/second, 20 cm/second, and 30 cm/second equivalents with the Reynolds numbers 114,229, and 457) were as follows: 0.65 +/- 0.37 mm (n = 1600) and 19.6 +/- 1.7 dyne/cm2; 46.1 +/- 8.1 dyne/cm2 and 80.1 +/- 16.8 dyne/cm2 (n = 1600). Curvature was 25 +/- 9 (m-1), resulting in Dean numbers 20 +/- 8; 46 +/- 16, and 93 +/- 33. Selection of data at the inner curvature of the right coronary artery provided wall thickness values of 0.90 +/- 0.41 mm (n = 100), and shear stress was 17 +/- 17, 38 +/- 44, and 77 +/- 54 dyne/cm2 (n = 100), whereas wall thickness values at the outer curve were 0.37 +/- 0.17 mm (n = 100) and shear stress values were 22 +/- 17, 60 +/- 44, and 107 +/- 79 dyne/cm2 (n = 100). These findings could be reconciled by an inverse relationship between wall thickness and shear stress for each velocity level under study. For the first time for human vessels in vivo, evidence is presented that low shear stress promotes atherosclerosis. As the method is nondestructive, it allows repeated measurements in the same patient and will provide new insights in the progress of atherosclerosis.

Cardiac depression after experimental air embolism in pigs: role of addition of a surface-active agent.

OBJECTIVE: Air bubbles entering the coronary artery may have harmful effects on cardiac function. From the physical point of view it is the relatively high surface tension of the blood-air interface which causes bubbles to trap in small vessels. The aim of the present study was to reduce depression of myocardial function from air embolism by lowering the surface tension of air bubbles. METHODS: The effect of using antifoam as a surface-tension-reducing agent on air bubble entrapment and cardiac function was investigated in 6 anesthetized pigs (27 +/- 1 kg) and analyzed using a two-compartment diffusion model. Air bubbles with a diameter of 150 microns were selectively injected into the left anterior descending coronary artery (LADCA) in a carrying fluid in the presence or absence of antifoam. Myocardial systolic segment shortening in the LADCA region (SS-LADCA) was measured by sonomicrometry. Presence of emboli was detected by measuring the amount of reverberation of ultrasound scattered by trapped air bubbles. RESULTS: SS-LADCA transiently decreased after injections of air bubbles in both the absence and presence of antifoam. However, in the presence of antifoam the regional depression recovered to normal sooner, the average depth of the depression was reduced, and bubbles from the embolized area cleared faster. These observations can be explained by a model derived from Laplace's law.

True reconstruction of vessel geometry from combined X-ray angiographic and intracoronary ultrasound data.

At present a rapidly expanding variety of methods appear to provide three-dimensional (3-D) reconstructions of blood vessels in a patient. Generally the results of such methods look very realistic. However, only a few produce a true 3-D reconstruction. We strongly suggest that for a true 3-D reconstruction of a blood vessel the following criteria should at least be fulfilled: (1) the arterial wall rather than the lumen must be reconstructed; (2) the spatially curved course of the vessel must be included; and (3) the orientation of local vessel wall characteristics, for example, plaque eccentricity, with respect to the luminal course must be correctly maintained. Currently, only methods combining biplane X-ray angiography and intravascular ultrasound imaging (IVUS) have succeeded in providing true 3-D reconstruction of a segment of a vessel. Accuracy of those reconstructions is derived from studies using phantoms having precisely known geometry. In patients, data on accuracy are more difficult to obtain. Nevertheless, a comparison can be made between the actual length of an IVUS pull-back trajectory and its reconstructed length showing relative differences of less than 3%. Further knowledge can be obtained by comparing simulated angiograms derived from the 3-D reconstruction with the real contrast angiograms. True 3-D reconstruction methods of the vessel wall and lumen, applicable in the individual patient, have become feasible and produce accurate results. Application of such a method will be helpful to understand immediate and long-term vessel remodelling induced by all types of catheter interventions and in the study of progression or regression of atherosclerotic wall disease.

Morphometric analysis in three-dimensional intracoronary ultrasound: an in vitro and in vivo study performed with a novel system for the contour detection of lumen and plaque.

Currently, automated systems for quantitative analysis by intracoronary ultrasound (ICUS) are restricted to the detection of the lumen. The aim of this study was to determine the accuracy and reproducibility of a new semiautomated contour detection method, providing off-line identification of the intimal leading edge and external contour of the vessel in three-dimensional ICUS. The system allows cross-sectional and volumetric quantification of lumen and of plaque. It applies a minimum-cost algorithm and the concept that edge points derived from previously detected longitudinal contours guide and facilitate the contour detection in the cross-sectional images. A tubular phantom with segments of various luminal dimensions was examined in vitro during five catheter pull-backs (1 mm/sec), and subsequently 20 diseased human coronary arteries were studied in vivo with 2.9F 30 MHz mechanical ultrasound catheters (200 images per 20 mm segment). The ICUS measurements of phantom lumen area and volume revealed a high correlation with the true phantom areas and volumes (r = 0.99); relative mean differences were -0.65% to 3.86% for the areas and 0.25% to 1.72% for the volumes of the various segments. Intraob-server and interobserver comparisons showed high correlations (r = 0.95 to 0.98 for area and r = 0.99 for volume) and small mean relative differences (-0.87% to 1.08%), with SD of lumen, plaque, and total vessel measurements not exceeding 7.28%, 10.81%, and 4.44% (area) and 2.66%, 2.81%, and 0.67% (volume), respectively. Thus the proposed analysis system provided accurate measurements of phantom dimensions and can be used to perform highly reproducible area and volume measurements in three-dimensional ICUS in vivo.

Utilization of translesional hemodynamics: comparison of pressure and flow methods in stenosis assessment in patients with coronary artery disease.

Aim of this study is the assessment of feasibility and clinical usefulness of a new index of stenosis severity, the slope of the instantaneous transstenotic pressure gradient/velocity relationship. Twenty-one patients scheduled for percutaneous revascularization procedures were studied with simultaneous measurement of poststenotic coronary pressure and flow velocity, in basal condition and during maximal hyperemia induced with intracoronary papaverine. Reliable measurements of the transstenotic pressure gradient/velocity relationship could be obtained in 11 patients. In 64% of the cases, a quadratic equation showed the best fit for the data. Steeper increases of the transstenotic pressure gradient at any given velocity increase were observed in the lesions with the smallest cross-sectional area measured with quantitative angiography. A comparison of this new index with coronary flow reserved, maximal hyperemic velocity, stenosis flow reserve derived from quantitative angiography, basal and hyperemic transstenotic pressure gradient and fractional flow reserve is presented and the relative merits of all these parameters are discussed. This pilot experience suggests that the instantaneous relationship between pressure gradient and flow velocity changes during the cardiac cycle can accurately characterize the stenosis hemodynamics in the catheterization laboratory.

Color quantification in angioscopic video images.

Colors in video representations of angioscopic images are up until now described by an human observer. Differences in settings of the monitor and the inherent poor ability of the human eye to classify colors objectively results in a very poor intraobserver as well as interobserver variability. A PC-based method is described to measure colors in a video image and to present the results in a novel C-diagram. Results with this method for standard calibrated colors are given. Possible sources of error are discussed and methods to minimize these errors are presented.

Luminal volume reconstruction from angioscopic video images of casts from human coronary arteries.

Intravascular angioscopy has been hampered by its limitation in quantifying obtained images. To circumvent this problem, a lightwire was used, which projects a ring of light onto the endoluminal wall in front of the angioscope. This investigation was designed to quantify luminal dimensions of casts from stenotic human coronary arteries and to investigate the feasibility of performing volume reconstruction. Angioscopic video recordings were made during simultaneous motorized pullback (2 mm/s) of an angioscopic catheter and light-emitting fiber through 4 epoxy casts from human coronary arteries. Quantification of the images was performed using a computerized cross-sectional area measurement system. The coronary casts were divided into cross-sectional segments of 4 to 10 mm in thickness, with the true volume of each segment determined by means of a microdispenser. Because of vessel curvature and luminal narrowing, complete visualization of the ring of light at all 1-mm-distant locations was only possible in 19 of 40 segments. For these 19 segments, linear regression analysis showed a good correlation between measured and true segmental volume (r = 0.97, y = 0.88x + 6.58 mm3, standard error of estimate = 3.48 mm3). The relative error in the measured segmental volumes was 3.9 +/- 7.1% (mean +/- SD). These initial results of endoluminal volume reconstruction demonstrate the feasibility of this technique in vitro with high accuracy and low variability, but further technical improvements are necessary to increase the success rate, especially in the quantitative assessment of vessels with complex morphology.

Spark erosion myectomy in hypertrophic obstructive cardiomyopathy.

The design features of the cutting electrode and the electrical characteristics of a monopolar electrosurgical device were specially adapted for performing a septal myectomy in patients with hypertrophic obstructive cardiomyopathy. Both the cutting behavior and electrode design were found to facilitate myectomy.

Mechanical features and in vivo imaging of a polymer stent.

A polyethylene-terephthalate (PETP, polyester), self-expanding, braided mesh stent has been developed for percutaneous (coronary) arterial implantation. In vitro measurements showed that the radial pressure delivered by this device was similar to a self-expanding, stainless steel stent. Due to hysteresis-like behaviour, it proved necessary to mount the polymer stent on the delivery system immediately before the placement procedure, and to select a diameter in the unconstrained condition, which was 60% larger than the diameter of the target vessel. Eight polyester stents were implanted in peripheral arteries of four pigs. Except for heparin during the implantation procedure, antithrombotic or antiplatelet drugs were not administered. After four weeks repeat angiography revealed that one of the stents was subtotally occluded. At autopsy, two other stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative angiographic assessment showed that the mean luminal diameters at the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 2.7 +/- 0.5 mm at four weeks after implantation. Intravascular ultrasound (IVUS) examination after 4 weeks could identify the individual struts of the stents, as well as their length. In addition, a description of the extent of neointimal hyperplasia was feasible. The IVUS assessment was validated by histological examination. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at four weeks. Imaging of stents by angiography and IVUS provided complementary information.

Heart function after injection of small air bubbles in coronary artery of pigs.

By its nature, vaporization of atherosclerotic plaques by laser irradiation or spark erosion may produce a substantial amount of gas. To evaluate the effect of gas embolism possibly caused by vaporization techniques, air bubbles with diameters of 75, 150, or 300 microns, each in a volume of 2 microliters/kg, were selectively injected subproximal in the left anterior descending coronary artery of seven anesthetized pigs (28 +/- 3 kg). Systemic hemodynamics such as heart rate, left ventricular pressure and its peak positive first derivative, and mean arterial pressure did not change after air injection, whereas there was a minor change in peak negative first derivative of left ventricular pressure. After injection of air bubbles there was a maximal relative reduction of systolic segment shortening (SS) in the myocardium supplied by the left anterior descending coronary artery of 27, 45, and 58% for 75-, 150-, and 300-microns bubbles, respectively, and a relative increase of postsystolic SS (PSS) of 148, 200, and 257% for 75-, 150-, and 300-microns bubbles, respectively. Recovery of SS and PSS started after 2 min and was completed after 10 min. A difference in SS and PSS changes between different bubble size injections could be demonstrated. From this study it is clear that depression of regional myocardial function after injection of air bubbles could pass unnoticed on the basis of global hemodynamic measurements.

Electrical nerve and muscle stimulation by radio frequency surgery: role of direct current loops around the active electrode.

Tissue cutting by electrosurgery is often accompanied with stimulation of nerves and muscles, despite the high frequency of the alternating current being applied. The main source of this stimulation is thought to be the generation of low frequency current by the nonlinear sparking process. However, measurement of this low-frequency current, in the generator electrode's circuit, showed relatively small values, barely sufficient to support this hypothesis. In this study more powerful low frequency current could be identified, indeed also originating from the nonlinear sparking process. Local direct and low frequency currents, at a level of tens of milliamperes, appeared to be generated between different sites of the active electrode-tissue interface. Probably these local currents have not been noticed before as they cannot be detected in the outer chain of generator, electrodes, and connecting wires. This finding may explain why most measures, intended to prevent stimulation by modifying this outer chain, had only limited success.

Development of a polymer endovascular prosthesis and its implantation in porcine arteries.

A polyethylene-terephthalate braided mesh stent has been developed for application in the (coronary) arterial tree. In vitro measurements showed that the radial pressure delivered by this device was in the same range as that of a stainless steel stent. Hysteresis-like behavior, however, occurred after constraining the polyester stent for a period of only 15 minutes on a delivery system for percutaneous implantation. This implies that the polymer stent must be mounted on this delivery system immediately before the placement procedure, and that either a diameter in the unconstrained condition must be selected, which is considerably larger than the diameter of the target vessel, or stent expansion has to be enhanced by balloon expansion. Taking into account the results obtained during the in vitro studies, we investigated the angiographic patency and histologic features after implantation of this polyester stent in peripheral arteries of pigs. In four animals eight stents were placed. Except for heparin during the implantation procedure only, antithrombotic or antiplatelet drugs were not administered. After 4 weeks repeat angiography was performed. Angiography revealed that five of the six correctly placed stents were patent. At autopsy, two additional patent stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative assessment showed that the mean luminal diameters of the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 3.1 +/- 0.3 mm at 4 weeks after implantation. Histology demonstrated an inflammatory reaction of variable severity around the stent fibers. Quantitative histologic measurements showed that the thickness of the neointima was 114 +/- 38 mum after 4 weeks. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. Hysteresis-like behavior of polyester stents, however, influences the selection of the nominal stent diameter as well as the forces exerted to the vessel wall. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at 4 weeks. The extent of neointimal proliferation was similar to that observed after placement of metal stents in swine, despite the presence of a more pronounced inflammatory reaction.