Cornelis J. Slager

Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms.

A computer-assisted technique has been developed to assess absolute coronary arterial dimensions from 35 mm cineangiograms. The boundaries of optically magnified and video-digitized coronary segments and the intracardiac catheter are defined by automated edge-detection techniques. Contour positions are corrected for pincushion distortion. The accuracy and precision of the edge detection procedure as assessed from cinefilms of contrast-filled acrylate (Perspex) models were -30 and 90 micrometers, respectively. The variability of the analysis procedure itself in terms of absolute arterial dimensions was less than 0.12 mm, and in terms of percentage arterial narrowing for coronary obstructions less than 2.74%. Short-, medium-, and long-term variability measurements were assessed from repeated coronary angiographic examinations performed 5 min, 1 hr, and 90 days apart, respectively. For all studies the mean differences in absolute diameters were less than 0.13 mm. The variability in obstruction diameter ranged from 0.22 mm for the best-controlled study (medium-term) to 0.36 mm for the least-controlled study (long-term); variability in reference diameter ranged from 0.15 to 0.66 mm, respectively. It is concluded that the biological variations are a source of major concern and that further attempts toward standardization of the angiographic procedure are seriously needed.

Relationship Between Neointimal Thickness and Shear Stress After Wallstent Implantation in Human Coronary Arteries

BackgroundIn-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 ResultsIn 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/m2. SS and neointimal thickness (Th) values were obtained with a resolution of 90° 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)×SS (mm) (P <0.05). ConclusionsThese 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.

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.

Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty.

The response of left ventricular function, coronary blood flow, and myocardial lactate metabolism during percutaneous transluminal coronary angioplasty (PTCA) was studied in a series of patients undergoing the procedure. From four to six balloon inflation procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD) and a total occlusion time of 252 +/- 140 sec. Analysis of left ventricular hemodynamics in 19 patients showed that the relaxation parameters, peak negative rate of change in pressure, and early time constants of relaxation, responded earliest to short-term coronary occlusion (peak effect at 17 +/- 7 sec) while other parameters, such as peak pressure, left ventricular end-diastolic pressure, and peak positive rate of change in pressure, responded more gradually, suggesting a progressive depression of myocardial mechanics throughout the procedure. Left ventricular angiograms, available for 14 patients, indicated an early onset of asynchronous relaxation concurrent with the early response in peak negative dP/dt and the time constant of early relaxation. All hemodynamic functions fully recovered within minutes after the end of PTCA. Mean blood flow in the great cardiac vein and proximal coronary sinus and the hyperemic response were measured in 20 patients. Before PTCA mean flow in the great cardiac vein was 69 +/- 17 ml/min and in the coronary sinus it was 129 +/- 34 ml/min. Reactive hyperemia (great cardiac vein) was 55% after the first PTCA and 91% after the third. A more pronounced reaction was observed when the residual functional coronary stenosis was reduced in subsequent dilatations. Arteriovenous lactate difference appeared constant during the first two occlusions (control +0.11 mmol/liter, first PTCA -0.87 mmol/liter, and second PTCA -0.82 mmol/liter) and did not increase during subsequent occlusions. Within minutes after the procedure lactate balance was again positive, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent dysfunction of global or regional myocardial mechanics, myocardial blood flow, or lactate metabolism after PTCA with four to six coronary occlusions of 40 to 60 sec.

Coronary Artery Dimensions from Cineangiograms-Methodology and Validation of a Computer-Assisted Analysis Procedure

To evaluate the efficacy of modern therapeutic procedures in the catheterization laboratory, the effects of vasoactive drugs, as well as the effects of short and long term interventions on the regression or progression of coronary artery disease, an objective and reproducible technique for the assessment of coronary artery dimensions was developed. This paper describes the methodology of such a computer-assisted analysis system, as well as the results from a validation study on the accuracy and precision. A region in a 35 mm cineframe encompassing a selected arterial segment is optically magnified and converted into video format by means of a specially constructed cinevideo converter and digitized for subsequent analysis by computer. Contours of the arterial segment are detected automatically on the basis of first and second derivative functions. Contour data are corrected for pincushion distortion; arterial dimensions are presented in mm, where the calibration factor is derived from a computer-processed segment of the contrast catheter. The accuracy and precision of the edge detection procedure as assessed from cinefilms of perspex models (%-D stenosis ⩽70 percent) filled with contrast agent were -30 and 90 μm, respectively. The variablity of the analysis procedure by itself in terms of absolute arterial dimensions was less than 0.12 mm, and in terms of percentage arterial narrowing for coronary obstructions less than 2.74 percent. It is concluded that this system allows the measurement of coronary arterial dimensions in an objective and highly reproducible way.

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.

The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications

American Heart Association type IV plaques consist of a lipid core covered by a fibrous cap, and develop at locations of eccentric low shear stress. Vascular remodeling initially preserves the lumen diameter while maintaining the low shear stress conditions that encourage plaque growth. When these plaques eventually start to intrude into the lumen, the shear stress in the area surrounding the plaque changes substantially, increasing tensile stress at the plaque shoulders and exacerbating fissuring and thrombosis. Local biologic effects induced by high shear stress can destabilize the cap, particularly on its upstream side, and turn it into a rupture-prone, vulnerable plaque. Tensile stress is the ultimate mechanical factor that precipitates rupture and atherothrombotic complications. The shear-stress-oriented view of plaque rupture has important therapeutic implications. In this review, we discuss the varying mechanobiologic mechanisms in the areas surrounding the plaque that might explain the otherwise paradoxical observations and unexpected outcomes of experimental therapies.

ECG-Gated Three-dimensional Intravascular Ultrasound Feasibility and Reproducibility of the Automated Analysis of Coronary Lumen and Atherosclerotic Plaque Dimensions in Humans

BACKGROUND Automated systems for the quantitative analysis of three-dimensional (3D) sets of intravascular ultrasound (IVUS) images have been developed to reduce the time required to perform volumetric analyses; however, 3D image reconstruction by these nongated systems is frequently hampered by cyclic artifacts. METHODS AND RESULTS We used an ECG-gated 3D IVUS image acquisition workstation and a dedicated pullback device in atherosclerotic coronary segments of 30 patients to evaluate (1) the feasibility of this approach of image acquisition, (2) the reproducibility of an automated contour detection algorithm in measuring lumen, external elastic membrane, and plaque+media cross-sectional areas (CSAs) and volumes and the cross-sectional and volumetric plaque+media burden, and (3) the agreement between the automated area measurements and the results of manual tracing. The gated image acquisition took 3.9+/-1.5 minutes. The length of the segments analyzed was 9.6 to 40.0 mm, with 2.3+/-1.5 side branches per segment. The minimum lumen CSA measured 6.4+/-1.7 mm2, and the maximum and average CSA plaque+media burden measured 60.5+/-10.2% and 46.5+/-9.9%, respectively. The automated contour-detection required 34.3+/-7.3 minutes per segment. The differences between these measurements and manual tracing did not exceed 1.6% (SD<6.8%). Intraobserver and interobserver differences in area measurements (n=3421; r=.97 to.99) were <1.6% (SD<7.2%); intraobserver and interobserver differences in volumetric measurements (n=30; r=.99) were <0.4% (SD<3.2%). CONCLUSIONS ECG-gated acquisition of 3D IVUS image sets is feasible and permits the application of automated contour detection to provide reproducible measurements of the lumen and atherosclerotic plaque CSA and volume in a relatively short analysis time.

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.

Effect of coronary occlusion during percutaneous transluminal angioplasty in humans on left ventricular chamber stiffness and regional diastolic pressure-radius relations

The effect of repeated (3 to 10 second) and transient (15 to 75 second) abrupt coronary occlusion on the global and regional chamber stiffness was studied in nine patients undergoing angioplasty of a single proximal left anterior descending coronary artery stenosis. The left ventricular high fidelity pressure and volume relation was obtained before and after the procedure as well as during coronary occlusion, after 20 seconds (n = 9) and after 50 seconds (n = 5). During ischemia, there was an upward shift of the pressure-volume relation. The nonlinear simple elastic constant of chamber stiffness increased from 0.0273 +/- 0.017 before angioplasty (mean +/- SD) to 0.0621 +/- 0.026 after 20 seconds of occlusion (p less than 0.05) and 0.0605 +/- 0.015 after 50 seconds of occlusion (p less than 0.01). In five patients, the postangioplasty value remained higher than the control value, but at the group level the mean value (0.0529 +/- 0.037) was not statistically different. The regional stiffness was determined from the changes in the length of six segmental radii during diastole, from the lowest diastolic to the end-diastolic pressure. The regional constant of elastic stiffness was unaffected in the nonischemic zone. In the adjacent and ischemic zones, the regional stiffness was increased during occlusion (p less than 0.05). These regional abnormalities in diastolic function persisted at the time of postangioplasty measurements, 12 minutes after the end of the procedure. This suggests that recovery of normal diastolic function after repeated ischemic injuries is delayed after restoration of normal blood flow and systolic function.