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BACKGROUND: Local wall shear stress (WSS) has an impact on local remodelling of the vessel wall. WSS in turn strongly depends on local geometry. Our aim was to characterize patterns of local wall shear stress associated with distinct types of remodelling in coronary arteries. Vessel size and flow rates are different between patients, however. To compare distribution patterns of WSS in analogy to fluid-dynamic modelling, non-dimensional WSS/area functions are calculated. METHODS: Right coronary arteries from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) were analyzed. Flow simulations were performed in three-dimensionally reconstructed coronary vessels from biplane angiographic projections. Local WSS was normalized as percentage of maximum value in a histogram (100 classes) and corresponding area was expressed as percentage of total area. RESULTS: The normalized WSS distribution was characterized by a single peak with a large lower tie in controls, a loss of the single peak and a stochastic distribution in AnCAD and a narrowing of the lower tie in CAD. Correct classification of 16/17 coronary arteries was feasible by Fisher's discriminant functions based on median WSS, mean diameter, percentage of area with WSS or=15 Pa. CONCLUSION: Normalized WSS distribution might be an efficient tool in comparing wall shear stress between different patient groups. Whether normalized WSS distribution curves are apt to grade severity of disease remains to be investigated.

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The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 162-168, . The duplicate article has therefore been withdrawn.

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OBJECTIVES: To validate in vivo a magnetic resonance imaging (MRI) method for measurement of pulmonary vascular resistance (PVR) and subsequently to apply this technique to patients with pulmonary hypertension (PHT). METHODS AND RESULTS: PVR was assessed from velocity encoded cine MRI derived pulmonary artery (PA) flow volumes and simultaneously determined invasive PA pressures. For pressure measurements flow directed catheters were guided under magnetic resonance fluoroscopy at 1.5 T into the PA. In preliminary validation studies (eight swine) PVR was determined with the thermodilution technique and compared with PVR obtained by MRI (0.9 (0.5) v 1.1 (0.3) Wood units.m2, p = 0.7). Bland-Altman test showed agreement between both methods. Inter-examination variability was high for thermodilution (6.2 (2.2)%) but low for MRI measurements (2.1 (0.3)%). After validation, the MRI method was applied in 10 patients with PHT and five controls. In patients with PHT PVR was measured at baseline and during inhalation of nitric oxide. Compared with the control group, PVR was significantly increased in the PHT group (1.2 (0.8) v 13.1 (5.6) Wood units.m2, p < 0.001) but decreased significantly to 10.3 (4.6) Wood units.m2 during inhalation of nitric oxide (p < 0.05). Inter-examination variability of MRI derived PVR measurements was 2.6 (0.6)%. In all experiments (in vivo and clinical) flow directed catheters were guided successfully into the PA under MRI control. CONCLUSIONS: Guidance of flow directed catheters into the PA is feasible under MRI control. PVR can be determined with high measurement precision with the proposed MRI technique, which is a promising tool to assess PVR in the clinical setting.

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BACKGROUND: The role of B cells and macrophages in microvascular disease after heart transplantation remains controversial. METHODS: Out of a total of 809 endomyocardial biopsies without evidence of acute cellular rejection (n = 422, 72 females and 350 males, median age 46 years), 393 without evidence of the quilty phenomenon were investigated zero to ten years after heart transplantation. Vascular reaction (endothelial cell swelling and vessel wall thickening) was graded by H&E staining, and immunohistochemistry was performed for T cells (clone UCHL1), B cells (clone L26) and macrophages (clone KP1) and evaluated semi-quantitatively (light microscopy x 200). RESULTS: Positive reaction for T cells and macrophages as well as evidence of endothelial cell swelling decreased with time after heart transplantation. Positive reactions for B cells were less frequent and increased slightly during the observation time, while vessel wall thickening dominated the last observation interval between the fourth and tenth years. Severity of vascular reaction was independent of immunohistochemical evidence of B cells or macrophages. CONCLUSIONS: While activation of the humoral and the non-specific immunological system is common after heart transplantation, microvascular alterations seem to develop independently of these findings.

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AIM: Graft vessel disease (GVD) is one of the main limiting factors to long-term survival after adult heart transplantation (HTx). The incidence of epicardial and microvascular GVD in paediatric patients was studied. METHODS: A total of 137 coronary angiographies from 130 paediatric HTx and heart and lung transplant (HLTx) patients (70 male, 60 female, aged 0-18 y) were evaluated according to the Stanford classification and its supplements (minor vessel alterations). In H&E stainings from right ventricular endomyocardial biopsies (EMB = 397), light microscopic diagnosis of acute cellular rejection (ISHLT classification) and vascular reaction (morphology of endothelial cells and vessel walls) was performed. RESULTS: Moderate rejection was present in 32.8% and severe rejection in 13.3% of EMB. Microvascular EC swelling was found in 33.5% and vessel wall thickening in 53.8% of EMB. The results of the coronary angiographic investigations were: Stanford lesions = 61.2%, peripheral obliterations = 52.5%, diameter fluctuations = 86.3%, pathologic tapering = 64.0%, calcifications = 10.8%. Long-term survivors (> or =5 y) showed macrovascular alterations in 78% of cases and microvascular alterations in 67% of cases. CONCLUSION: The development of micro- and macrovascular GVD is one of the predominant complications in long-term survivors after paediatric HTx and HLTx.

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AIMS: The scope of this study was to assess the potential value of pulmonary venous flow diastolic deceleration time to predict end-diastolic pressure and stratify patients with regard to elevation of left ventricular end-diastolic pressures. METHODS AND RESULTS: In 174 consecutive patients, pulmonary venous flow diastolic deceleration time was determined and compared with left ventricular end-diastolic pressures measured invasively. The sample was randomly divided into two subgroups of equal size for modelling of prediction and independent testing of the model. Predicted left ventricular end-diastolic pressures calculated from pulmonary venous flow diastolic deceleration time (left ventricular end-diastolic pressures=-10.87 + 5261/pulmonary venous flow diastolic deceleration time) agreed well with measured left ventricular end-diastolic pressures (mean difference: -1.3 +/- 3.4 mmHg). The correlation of left ventricular end-diastolic pressures with pulmonary venous flow diastolic deceleration time is fair (r=0.73989). A value of pulmonary venous flow diastolic deceleration time <220 ms is suggestive of elevated left ventricular end-diastolic pressures and should be monitored. A value of pulmonary venous flow diastolic deceleration time <190 ms predicts elevated left ventricular end-diastolic pressures. A value of pulmonary venous flow diastolic deceleration time <165 ms predicts severely elevated left ventricular end-diastolic pressures. With 190 ms as a cut-off value for elevated and 165 ms for severely elevated left ventricular end-diastolic pressures, cross-table analysis classifies all patients with normal left ventricular end-diastolic pressures correctly. No patient with severe elevation (<18 mmHg) of left ventricular end-diastolic pressures is classified as normal (chi2=102, P<0.0001). CONCLUSION: Pulmonary venous flow diastolic deceleration time is an appropriate non-invasive measurement to stratify patients with respect to elevation of left ventricular end-diastolic pressures.

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OBJECTIVE: to investigate the effect of clopidogrel combined with aspirin or aspirin alone on fibromyointimal hyperplasia (FIMH) in a bypass model with native vein grafts (NVG) and biocompound grafts (BCG). DESIGN: twelve Beagle dogs were randomised into two equal groups. In each animal NVG and a BCG were interposed in the common carotid arteries. Postoperatively, Group 1 received clopidogrel (200 mg/d) and aspirin (100 mg/d) and Group 2 received aspirin (100 mg/d) alone. METHODS: the BCG was constructed by sheathing the ipsilateral jugular vein with highly flexible metal mesh tubing. After 30 days the grafts were harvested and pressure fixed. FIMH was determined by morphometry. RESULTS: the average wall thickness of the BCG was significantly lower than that of the NVG in both groups (0.26 (SD)0.02 mm vs 0.47 (SD)0.15 mm, p = 0.04 and 0.28 (SD)0.05 mm vs 0.70 (SD)0.29 mm, p = 0.01, respectively). For BCG treated with aspirin, the wall cross section area was lower (5.0 (SD)0.6 mm(2)vs 9.1 (SD)3.3 mm(2), p = 0.02) and the lumen larger (25.2 (SD)5.9 mm(2)vs 9.7 (SD)3.4 mm(2), p < 0.01) than for the NVG. There was also a difference in the lumen cross section area of the NVG, which was larger after combined therapy with clopidogrel and aspirin (17.9 (SD)7.8 mm(2)vs 9.7 (SD)3.4 mm(2), p = 0.04). CONCLUSIONS: in this dog model the sheathing of vein grafts effectively prevents FIMH following bypass surgery. Clopidogrel is effective in NVG.

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BACKGROUND: Invasive screenings at predefined time intervals for acute rejection and transplant coronary artery disease (TxCAD) are standard procedures. However, cardiac biopsies and catheterizations are distressing and risky for the patients and are also costly. We assessed the reliability of pulsed-wave tissue Doppler imaging (PW-TDI) for the timing of invasive examinations in heart recipients in an attempt to avoid unnecessary endomyocardial biopsies (EMBs) and catheterizations. METHODS AND RESULTS: PW-TDI obtained at the basal left ventricular posterior wall before 408 EMBs and 293 catheterizations was tested for its diagnostic value regarding rejection and TxCAD with the use of International Society of Heart and Lung Transplantation biopsy grading, coronary angiography, and intravascular ultrasound as standards. Early diastolic peak wall motion velocity and relaxation time showed high sensitivities for clinically relevant rejection diagnosis (90.0% and 93.3%, respectively). The negative and positive predictive values for rejection of diastolic parameter changes appeared high enough (up to 96% and 92%, respectively) to allow a reliable noninvasive PW-TDI monitoring with efficiently timed, instead of routinely scheduled, EMBs. At definite cutoff values for systolic parameters, the probability for TxCAD reached 92% to 97%. The Fisher classification functions allowed TxCAD exclusion with 80% probability. CONCLUSIONS: Without diastolic parameter changes, acute rejection can be practically excluded, and serial PW-TDI can save patients from routine EMBs. The high specificity and negative predictive value for TxCAD of reduced systolic peak velocities and extended systolic time allow optimized timed catheterizations. Peak systolic velocity and systolic time allow diagnostic classifications that enable patients without known TxCAD but with high risk for catheterization to be spared routine angiographies.

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Coronary artery bypass graft (CABG) operation for coronary artery disease with different types of grafts has a large clinical application world wide. Immediately after this operation patients are usually relieved of their chest pain and have improved cardiac function. However, after a while, these bypass grafts may fail due to for example, neointimal hyperplasia or thrombosis. One of the causes for this bypass graft failure is assumed to be the blood flow with low wall shear stress. The aim of this research is to estimate the wall shear stress in a graft and thus to locate areas were wall shear stress is low. This was done with the help of a blood flow computer model. Post-operative biplane angiograms of the graft were recorded, and from these the three-dimensional geometry of the graft was reconstructed and imported into the computational fluid dynamics (CFD) program FLUENT. The stationary diastolic flow through the grafts was calculated, and the wall shear stress distribution was estimated. This procedure was carried out for one native vessel and two different types of bypass grafts. One bypass graft was a saphenous vein and the other one was a varicose saphenous vein encased in a fine, flexible metal mesh. The mesh was attached to give the graft a defined diameter. The computational results show that each graft has distinct areas of low wall shear stress. The graft with the metal mesh has an area of low wall shear stress (< 1 Pa, stationary flow), which is four times smaller than the respective areas in the other graft and in the native vessel. This is thought to be caused by the smaller and more uniform diameter of the metal mesh-reinforced graft.

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BACKGROUND: Changes in renal blood flow are considered to play a significant role in the induction and maintenance of kidney failure, but are difficult to monitor with currently available techniques. The objective was to validate renal flow measurements with Doppler guidewires and to apply this technique to assess dose and time dependency of the renal vascular effects of norepinephrine (NE). METHODS: In 10 anesthetized pigs, flow velocity in renal arteries (FVart) and veins (FVvein) and volumetric renal blood flow (VBF) were measured before and after intravenous bolus application of incremental doses of NE (2 to 200 microg). RESULTS: FVart curves exactly reflected the changes in VBF. Beat-to-beat analysis revealed a strong linear correlation over a mean VBF range of less than 0.05 to 0.35 L/min (median correlation coefficient with FVart, r = 0.998), and significant but less close relationships were also found between VBF and FVvein. Ten seconds after the administration of 200 microg NE, FVart dropped from 71 to 6 cm/sec and was 90% reversible after 48 seconds. Similarly, the renal vascular resistance temporarily rose from 988 to 13711 mm Hg. min/L. In contrast, NE-induced increases in systemic vascular resistance were on average a maximum of 1.5-fold but persisted for more than 60 seconds. CONCLUSIONS: Doppler flow measurements in the renal artery provide an excellent surrogate of volumetric blood flow, which may be useful for continuous monitoring of renal hemodynamics. The renal vasculature is more sensitive when compared with the systemic vasculature, but also appears to evoke more efficient counter-regulatory mechanisms in response to NE.

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PURPOSE: To report the increased efficacy of oversized, overlapping stents to treat an internal carotid artery (ICA) dissecting aneurysm. CASE REPORT: A 55-year-old woman presented with reduced consciousness, aphasia, and right-sided hemiplegia owing to an infarction of the left middle cerebral artery territory documented by computed tomography. Digital subtraction angiography disclosed an extracranial dissection of the left ICA with a pseudoaneurysm. Two self-expanding Wallstents were placed, bridging the dissected segment and overlapping at the level of the aneurysm neck. Immediate arteriography showed remarkably reduced filling of the pseudoaneurysm. Serial arteriograms performed 6 days and 9 and 20 months after stenting documented the disappearance of the pseudoaneurysm without appreciable intimal hyperplasia of the vessel w all. CONCLUSIONS: Reducing stent porosity by overlapping the devices causes significant hemodynamic changes inside the aneurysm sac, accelerating intra-aneurysmal thrombosis.

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AIMS: Goals of the study were the assessment of the correlation between flow-dependent and contrast-related vasodilatation, comparison of iodixanol to iopromide and evaluation of the impact of plaque on vasodilatation in coronary arteries. METHODS AND RESULTS: A controlled randomized paired cross-over comparison between iodixanol (320mgI.ml(-1)) and iopromide (300mgI.ml(-1)) was performed in 10 consecutive patients. Vessel area (Visions Five-64 F/X intra-vascular ultrasound-catheter, Endosonics and blood flow velocity measurements (0.014inches Doppler guide wire, Cardiometrics were recorded simultaneously at an identical position, at baseline, after i.c. bolus injection of 10ml physiologic saline (flow-dependent vasodilatation), and after application of contrast agent 1 and contrast agent 2 as randomized. The action of iodixanol and iopromide on the vascular wall did not differ and was equal to local flow-dependent vasodilatation induced by a saline bolus (correlation 0.95-- 0.98). The increase in local luminal area after injection of saline, iodixanol and iopromide in morphologically normal vessels (approximately 2.5mm(2)) was absent in atherosclerotic segments. Both contrast agents and saline demonstrated a nearly identical flow increase. CONCLUSION: If iodixanol or iopromide are used as contrast agents, contrast-related vessel area increase in vivo seems to be endothelium-dependent.

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UNLABELLED: The investigation was to elucidate the role of the reduction of extravascular pulmonary fluid in the immediate symptomatic improvement and its impact on hemodynamics in patients with mitral stenosis treated by percutaneous transluminal valvuloplasty. METHODS: In a prospective study of 12 patients with severe mitral stenosis extravascular pulmonary fluid volume was determined by a combined dye and thermodilution technique (COLD Z-021(TM) Version 5.x, Pulsion((R))) before and after valvuloplasty. Cardiac output, left atrial pressures, atrial V-waves, diastolic transmitral gradients and their respiratory changes were measured. Dyspnea was assessed by validated questionnaires. RESULTS: Symptomatic improvement correlated (r=0. 808) with a decrease of extravascular lung water, but not with either an increase or a decrease of cardiac output or left atrial filling pressures. The decrease of the lung water index may be predicted from the lung water index before valvuloplasty, the final left atrial mean pressure and the cardiac index prior to intervention. The change of the mean difference between inspiratory and expiratory mitral gradient demonstrated a significant inverse correlation with the change of mean left atrial filling pressures (r=-0.778) and with extravascular lung water after valvuloplasty (r=-0.871). CONCLUSION: There is a complex relationship between left atrial filling pressures, extravascular lung water, respiratory changes of gradients, and dyspnea that need further investigation.

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BACKGROUND: Intracoronary ultrasound (ICUS) imaging is the most sensitive method for the early detection and serial evaluation of vasculopathy of transplants. Both lack of agreement between observers and lack of agreement between serial, independent pullback procedures (repeatability), which can result in a variable intraluminal catheter position may limit the reproducibility of ICUS measurements. OBJECTIVE: To evaluate the reproducibility of serial measurements of standard linear and area cross-sectional coronary dimensions in patients with non-obstructive transplant vasculopathy. METHODS: We performed ICUS imaging of patients without angiographic evidence of obstructive epicardial coronary artery disease after heart transplantation. A 30 MHz phased-array transducer was used. Two independent pullbacks of the left anterior descending coronary artery were performed and recorded on CD-ROM for off-line quantitative analysis of the most severely diseased site. Agreement of observers and repeatability of serial measurements were calculated by the use of linear regression analysis and Bland-Altman plots. RESULTS: Regarding agreement of observers, correlation coefficients for intra-observer agreement ranged from r = 0.98 to r = 0.99; those for interobserver agreement ranged from r = 0.87 to r = 0.98. Serial measurements of the identical coronary artery cross-section within independent catheter pullback procedures were possible for 104 of 112 target lesions (92.90/%). Correlation coefficients ranged from r = 0.91 to r = 0.97 (for lumen diameter r = 0.91, for lumen area r = 0.93, for vessel diameter r = 0.91, for vessel area r = 0.97, for thickness of plaque r = 0.96 and for area of plaque 0.94). The mean difference of measurements was around zero for all parameters with SD from 0.13 to 0.4 mm for linear parameters and from 1.53 to 1.82 mm2 for area parameters. CONCLUSION: Serial intravascular ultrasound measurements are highly reproducible without any evidence of systematic error and a SD of differences of measurements beyond the maximal spatial resolution of currently available intravascular ultrasound catheters.

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