Percent Luminal Stenosis Research Articles

Comparison of Photon-counting Detector and Energy-integrating Detector CT for Visual Estimation of Coronary Percent Luminal Stenosis.

Background Compared with energy-integrating detector (EID) CT, the improved resolution of photon-counting detector (PCD) CT coupled with high-energy virtual monoenergetic images (VMIs) has been shown to decrease calcium blooming on images in phantoms and cadaveric specimens. Purpose To determine the impact of dual-source PCD CT on visual and quantitative estimation of percent diameter luminal stenosis compared with dual-source EID CT in patients. Materials and Methods This prospective study recruited consecutive adult patients from an outpatient facility between January and March 2022. Study participants underwent clinical dual-source EID coronary CT angiography followed by a research dual-source PCD CT examination. For PCD CT, multienergy data were used to create VMIs at 50 and 100 keV. Two readers independently reviewed EID CT images followed by PCD CT images after a washout period. Readers visually graded the most severe stenosis in terms of percent diameter luminal stenosis for the left main, left anterior descending, right, and circumflex coronary arteries, unblinded to scanner type. Quantitative measures of percent stenosis were made using commercial software. Visual and quantitative estimates of percent stenosis were compared between EID CT and PCD CT using the Wilcoxon signed-rank test. Results A total of 25 participants (median age, 59 years [range, 18-78 years]; 16 male participants) were enrolled. On EID CT images, readers 1 and 2 identified 39 and 32 luminal stenoses, respectively, with a percent diameter luminal stenosis greater than 0%. Visual estimates of percent stenosis were lower on PCD CT images than EID CT images (reader 1: median 20.6% [IQR, 8.8%-61.2%] vs 31.8% [IQR, 12.9%-69.7%], P < .001; reader 2: 6.5% [IQR, 0.4%-54.1%] vs 22.9% [IQR, 1.8%-67.4%], P = .002). No difference was observed between EID CT and PCD CT for quantitative measures of percent stenosis (median difference, -1.5% [95% CI: -3.0%, 2.5%]; P = .51). Conclusion Relative to using EID CT, using PCD CT led to decreases in visual estimates of percent stenosis. © RSNA, 2023 See also the editorial by Murphy and Donnelly in this issue.

Vulnerable plaque of the petrous internal carotid artery in embolic stroke of undetermined source.

The association between nonstenotic plaque at the petrous internal carotid artery (ICA) and embolic stroke of undetermined source (ESUS) remains unknown. We aimed to test the hypothesis that the presence of a larger build-up of petrous plaque is more prevalent in the ipsilateral versus the contralateral side among ESUS patients without plaque in the intracranial and proximal ICA. From a total of 243 patients with ESUS and 160 patients with small-vessel disease (SVD) without proximal ICA plaque, we enrolled 88 ESUS and 103 SVD patients without ipsilateral nonstenotic intracranial and proximal ICA plaque in the present study. Targeting the petrous segment of the ICA on two sides, plaque burden including plaque thickness, lumen area, vessel area, wall area, and percentage of luminal stenosis, and composition features (presence/absence of the ruptured fibrous cap, ulcer plaque, thrombus, discontinuity of plaque surface [DPS], intraplaque hemorrhage and complicated plaque) were assessed by high-resolution magnetic resonance imaging. We found a higher prevalence of petrous plaque thickness ≥3.5 mm ipsilateral versus contralateral to the stroke (25/88 [28.4%] vs. 12/88 [13.6%], odds ratio [OR] 3.60, 95% confidence interval [CI] 1.34-9.70), but this imbalance was not seen in SVD. In patients with plaque thickness ≥3.5 mm, the presence of DPS (OR 4.05, 95% CI 1.11-14.78) and complicated plaque (OR 5.00, 95% CI 1.10-22.82) was more closely related to an index ESUS, a finding that was not evident in the subgroup with petrous plaque <3.5 mm (p for interaction=0.027). The present study provided the first evidence supporting a potential etiological role of vulnerable petrous plaque in ESUS.

Endovascular Intervention in Internal Carotid Artery Blunt Cerebrovascular Injury: An EAST Multicenter Study.

Use of endovascular intervention (EI) for blunt cerebrovascular injury (BCVI) is without consensus guidelines. Rates of EI use and radiographic characteristics of BCVI undergoing EI nationally are unknown. A post-hoc analysis of a prospective, observational study at 16 U.S. trauma centers from 2018 to 2020 was conducted. Internal carotid artery (ICA) BCVI was included. The primary outcome was EI use. Multivariable logistic regression was performed for predictors of EI use. From 332 ICA BCVI included, 21 (6.3%) underwent EI. 0/145 (0%) grade 1, 8/101 (7.9%) grade 2, 12/51 (23.5%) grade 3, and 1/20 (5.0%) grade 4 ICA BCVI underwent EI. Stroke occurred in 6/21 (28.6%) ICA BCVI undergoing EI and in 33/311 (10.6%) not undergoing EI (P = .03), with all strokes with EI use occurring prior to or at the same time as EI. Percentage of luminal stenosis (37.75 vs 20.29%, P = .01) and median pseudoaneurysm size (9.00mm vs 3.00mm, P = .01) were greater in ICA BCVI undergoing EI. On logistic regression, only pseudoaneurysm size was associated with EI (odds ratio 1.205, 95% CI 1.035-1.404, P = .02). Of the 8 grade 2 ICA BCVI undergoing EI, 3/8 were grade 2 and 5/8 were grade 3 prior to EI. Of the 12 grade 3 ICA BCVI undergoing EI, 11/12 were grade 3 and 1/12 was a grade 2 ICA BCVI prior to EI. Pseudoaneurysm size is associated with use of EI for ICA BCVI. Stroke is more common in ICA BCVI with EI but did not occur after EI use.

Factors associated with stroke formation in blunt cerebrovascular injury: An EAST multicenter study.

Stroke risk factors after blunt cerebrovascular injury (BCVI) are ill-defined. We hypothesized that factors associated with stroke for BCVI would include medical therapy (i.e., Aspirin), radiographic features, and protocolization of care. An Eastern Association for the Surgery of Trauma-sponsored, 16-center, prospective, observational trial was undertaken. Stroke risk factors were analyzed individually for vertebral artery (VA) and internal carotid artery (ICA) BCVI. Blunt cerebrovascular injuries were graded on the standard 1 to 5 scale. Data were from the initial hospitalization only. Seven hundred seventy-seven BCVIs were included. Stroke rate was 8.9% for all BCVIs, with an 11.7% rate of stroke for ICA BCVI and a 6.7% rate for VA BCVI. Use of a management protocol (p = 0.01), management by the trauma service (p = 0.04), antiplatelet therapy over the hospital stay (p < 0.001), and Aspirin therapy specifically over the hospital stay (p < 0.001) were more common in ICA BCVI without stroke compared with those with stroke. Antiplatelet therapy over the hospital stay (p < 0.001) and Aspirin therapy over the hospital stay (p < 0.001) were more common in VA BCVI without stroke than with stroke. Percentage luminal stenosis was higher in both ICA BCVI (p = 0.002) and VA BCVI (p < 0.001) with stroke. Decrease in percentage luminal stenosis (p < 0.001), resolution of intraluminal thrombus (p = 0.003), and new intraluminal thrombus (p = 0.001) were more common in ICA BCVI with stroke than without, while resolution of intraluminal thrombus (p = 0.03) and new intraluminal thrombus (p = 0.01) were more common in VA BCVI with stroke than without. Protocol-driven management by the trauma service, antiplatelet therapy (specifically Aspirin), and lower percentage luminal stenosis were associated with lower stroke rates, while resolution and development of intraluminal thrombus were associated with higher stroke rates. Further research will be needed to incorporate these risk factors into lesion specific BCVI management. Prognostic and Epidemiologic, Level IV.

Study on Vitamin D deficiency in patients of diabetes mellitus presenting with Acute Coronary syndrome in a tertiary care hospital in South India

Background: Vitamin D, a fat-soluble vitamin has its receptor present in myriad of tissues and it modulates multiple cellular processes. Vitamin D deficiency is reported to be associated with coronary artery disease. Cardiovascular disease is the leading cause of mortality worldwide.&#x0D; Aims and Objective: The primary outcome was to investigate if there is a correlation of 25-OH levels with the percentage of luminal stenosis, as measured with coronary angiogram. The secondary outcome was to determine the differences in angiographically proven luminal stenosis across categories of 25-OH vitamin D levels.&#x0D; Materials and Methods: Thirty patients with acute coronary syndrome with diabetes mellitus were included in this cross-sectional descriptive study. All patients were tested for fasting vitamin D levels, fasting blood sugar, HbA1C and serum creatinine. Detailed history of the patients was recorded. Data was analyzed by the statistical software SPSS version 19 and p value &lt;0.05 was considered significant. Statistical tests like Chi- square, independent t test and log regression was used.&#x0D; Results: In this study 30 patients undergoing coronary angiography for acute coronary syndrome, Vitamin D levels showed severe deficiency in 6.7% (2) cases while mild deficiency was seen in 50% of the cases. Patients with single vessel disease on the coronary angiogram had lower mean HbA1C (9.18) levels in our study. Patients with triple vessel disease had poorly controlled mean HbA1C levels (10.42).&#x0D; Conclusion: In this study we did not find any significant difference between the serum Vitamin D deficiency levels with patients with angiographic severity of the coronary artery disease. Patients with poorly controlled diabetes mellitus had more severe angiographic proven coronary artery disease.

Abstract TP106: Adventitial T Cell Infiltrates Are Related to Brain Atherosclerosis in Hiv-infected Individuals, but Not With Advanced Immunosuppression

Background: HIV-infected individuals may display chronic brain inflammation. It is unclear whether this inflammation may play a role in brain arterial pathologies that predispose patients with HIV to stroke. We tested the hypothesis that T cell infiltrates would be associated with brain arterial pathology. Methods: Large brain arteries from 162 patients (84 with HIV) were used in immunohistochemical analysis to detect CD3, a pan T cell marker. A semi-quantitative score of 0 to 3 (absent, mild, moderate, severe) was created by visually rating CD3+ cells within each arterial layer (intima, media, and adventitia). Arterial stenosis, lumen-to-wall ratio and presence of atherosclerosis were measured in each arterial segment of the circle of Willis using previously reported methods of good to excellent reliability. All models were adjusted for co-dependence between arteries of the same subject as well as for age, sex, ethnicity, vascular risks factors, cocaine use and artery type and location. Results: Brain arteries from HIV+ individuals had lower adventitial CD3 scores than HIV- (B = -1.65, p = 0.004). Further stratification demonstrated that the decreased arterial CD3 score was significant only among HIV+ subjects with premortem CD4 counts &lt; 200 cells/μl (B = -2.28, p &lt;0.001). Among HIV+ individuals with premortem CD4 counts ≥ 200 cells/μl, CD3 arterial scores were associated with brain atherosclerosis (B = 0.74, p=0.04). Independent of HIV status, CD3 score was associated with decreased lumen-to-wall ratio (B = -0.37, p = 0.02) and percentage luminal stenosis (B = 1.99, p = 0.004). Among HIV+ cases, higher CD3 score was noted with higher CD4 count at death (per 50, B=0.43, P=0.001), hypertension (B=7.14, P&lt;0.001), male sex (B=6.29, P=&lt;0.001) and prior opportunistic infections (B=3.24, P=0.008) while a lower CD3 score was noted among diabetics (B=-5.36, P&lt;0.001) and reported use of antiretroviral at death (B=-1.39, P=0.01). Conclusions: Among HIV+ individuals with premortem CD4 counts ≥ 200, there exists an association between brain arterial lymphocytic activity with atherosclerosis. These findings may suggest a role for lymphocytic inflammation in HIV-related atherosclerosis in the setting of immune reconstitution.

Fractional Flow Assessment for the Evaluation of Intracranial Atherosclerosis: A Feasibility Study

Purpose: Current studies on endovascular intervention for intracranial atherosclerosis select patients based on luminal stenosis. Coronary studies demonstrated that fractional flow measurements assess ischemia better than anatomical stenosis and can guide patient selection for intervention. We similarly postulated that fractional flow can be used to assess ischemic stroke risk. Methods: This was a feasibility study to assess the technical use and safety of applying a pressure guidewire to measure fractional flow across intracranial stenoses. Twenty patients with severe intracranial stenosis were recruited. The percentage of luminal stenosis, distal to proximal pressure ratios (fractional flow) and the fractional flow gradients across the stenosis were measured. Procedural success rate and safety outcomes were documented. Results: All 20 patients had successful crossing of stenosis by the pressure guidewire. Ten patients underwent angioplasty, and 5 had stenting performed. There was one perforator stroke, but not related to the use of the pressure wire. For the 13 patients with complete pre- and postintervention data, the mean preintervention stenosis, fractional flow and translesional pressure gradient were 76.2%, 0.66 and 29.9 mm Hg, whilst the corresponding postintervention measurements were 24.7%, 0.88 and 10.9 mm Hg, respectively. Fractional flow (r = -0.530, p = 0.001) and the translesional pressure gradient (r = 0.501, p = 0.002) only had a modest correlation with the luminal stenosis. Conclusion: Fractional flow measurement by floating a pressure guidewire across the intracranial stenosis was technically feasible and safe in this study. Further studies are needed to validate its use for ischemic stroke risk assessment.

Atherosclerosis involving the cerebral and coronary vessels: A comparative analysis

Patients with ischemic heart diseases are more likely to have stroke than those without and ischemic heart disease is a frequent cause of death among stroke survivors. The risk factors for both are the same. We compared the atherosclerotic pathology in the cerebral, coronary and carotid vessels. A total of 50 autopsy cases were selected for the Baker scoring system The median Baker score ranged was 26.1 in our study. All cases showing severe atherosclerosis of the intracranial vessels were compared with the coronary arteries and the carotid arteries. The percentage of luminal stenosis, severity of stenosis, pattern of narrowing, composition (Fibrous, Fibrofatty, Fatty), inflammation-type and location, calcification, thinning of the vessel wall, microaneurysm formation, thrombus, intraplaque haemorrhage and neovascularisation was documented in detail in cases. Of the 14 cases showing severe intracranial atherosclerosis most also showed severe coronary atherosclerosis but mild carotid atherosclerosis. Infarcts were seen in 7 cases and all had history of hypertension.

Abstract 14702: Evaluation of Inflammation in Carotid Disease by New Imaging Modalities: Implications From 18-FDG PET/CT and Microwave Radiometry

Background and Purpose: Nowadays, 18F fludeoxyglycose Positron Emmision Tomography/computed tomography (18F-FDG PET/CT) is the leading modality for tracing inflammation within atherosclerotic plaques in vivo, but patients’ exposure to radiation, costs and availability limit its widespread use. We hypothesize that microwave radiometry (MWR), a safe noninvasive method allowing in vivo estimation of atherosclerotic process by measuring temperatures of tissues could be an accurate alternative tool for assessing lesional inflammation. Therefore, the aim of the present study was to investigate the relationship between temperature differences and FDG uptake assessed by MWR and 18F-FDG PET/CT respectively, in patients with significant carotid disease. Methods: Consecutive patients, scheduled for carotid endarterectomy due to significant carotid artery (CA) stenosis, underwent 18F-FDG PET/CT and MWR. PET/CT images were acquired 90 min after FDG injection. FDG uptake was measured as maximal standardized uptake value (SUVmax) in consecutive axial slices starting at the bifurcation and extending 2 cm superiorly and 2 cm inferiorly. During MWR evaluation, ΔΤ (maximal temperature across the carotid artery minus minimum) was calculated over the respective carotid segments. Results: In total, 44 CAs from 22 patients (18 male) were studied. There was a significant positive correlation between ΔT and SUVmax values in the operated arteries and also between the same parameters in all 44 vessels (R=0.44, p=0.05 and R=0.44, p=0.005, respectively). Operated and non-operated CAs demonstrated similar ΔT and SUVmax values (0.57±0.19 vs 0.59±0.17 °C, p=0.67 and 2.18±0.44 vs 2.28±0.41, p=0.48 respectively). In addition, there was no correlation between the degree of angiographic stenosis and ΔT values (R=0.07, p=0.65) or between lesional SUV measurements and the percentage of luminal stenosis (R=0.10, p=0.55). Conclusions: There is a significant correlation between FDG uptake and thermal heterogeneity, indicating that MWR is a promising marker of plaque inflammation. Moreover, there is discrepancy between stenosis severity and inflammation intensity assessed by FDG uptake and MWR, highlighting the diversity of processes involved in CA atherosclerosis.

Abstract 16675: Intraplaque Hemorrhage-induced Atherosclerotic Plaque Progression as the Bridge Between Intact and Ulcerated Plaques: An Imaging-based Natural History Study

Introduction: Previous studies have associated intraplaque hemorrhage (IPH) with future ischemic events, of which the mechanisms are less understood. Hypothesis: Understanding morphological features and progression behaviors of plaques with and without IPH would allow us to define the role of IPH in the natural history of atherosclerosis. Methods: In an ongoing study, asymptomatic subjects with 16-79% stenosis on ultrasound underwent 3-dimensional carotid MRI. Those with carotid plaque(s) on MRI were recruited and a follow-up scan was performed 1-year later using the same protocol. Individual plaques (maximum thickness&gt;1.5 mm) within scan coverage were identified in bilateral carotids, of which morphological data were collected at baseline and plaque progression was determined by comparing both scans while blinded to the time sequence. Results: Twenty-nine subjects have completed the study. A total of 64 de novo plaques were identified, of which 15 (23.4%) demonstrated IPH. Plaques with IPH are more likely to have an ulcerated surface than those without IPH (60.0% vs. 8.2%, odds ratio: 16.9 [3.9, 72.3]). Furthermore, there was a stepwise progression in baseline morphological measures from IPH-/ulcer- plaques to IPH+/ulcer- plaques and to ulcer+ plaques (Table), suggesting that IPH+/ulcer- plaques may be at the intermediate stage between IPH-/ulcer- and ulcer+ plaques. During the 1-year period, IPH+/ulcer- plaques had significantly greater increases in mean wall thickness and percent luminal stenosis compared to IPH-/ulcer- plaques, indicating further progression towards ulcer+ plaques. In contrast, ulcer+ plaques, as the most stenotic group, showed little plaque burden change on average. Conclusions: Collectively, our data support the conjecture that IPH promotes plaque progression and appears to be an intermediate step toward surface ulceration. IPH could be a critical step in phenotype transition from asymptomatic to symptomatic plaques.

Using aortic distensibility index to detect coronary stenosis

Objective The aortic distensibility index, as a measure of vascular function, can serve as a marker of coronary artery disease severity. This study explores the feasibility of using the non-invasively measured index as an indicator of severity of coronary stenosis.Methods One hundred patients with normal left ventricular systolic function were prospectively enrolled. They were subjected to assessment of aortic distensibility using computed tomographic angiography and transthoracic echocardiography. Coronary artery disease severity and coronary artery calcium score were assessed.Results The mean age of the whole study cohort was 58 ± 9 years, 63 (63%) being males. A signifi cant inverse correlation was found between aortic distensibility measured using computed tomographic angiography and patients’ age, systolic blood pressure, coronary artery calcium score and severity of coronary artery disease (percent luminal stenosis). However, there was no statistical correlation with the number of diseased coronary arteries. A strong direct correlation was recorded upon comparing aortic distensibility index values obtained using computed tomographic angiography and transthoracic echocardiography (r = 0.325, P= 0.004). Receiver operating characteristic curve analysis revealed that an echocardiography-derived aortic distensibility index value of ≤ 6.65% is associated with signifi cant (≥ 50% luminal stenosis) coronary artery disease with a sensitivity of 83%, specifi city of 93%, positive predictive value of 97% and negative predictive value of 65%.Conclusion Non-invasive assessment of aortic distensibility indices is a feasible procedure to predict signifi cant atherosclerotic coronary artery disease. Lower values are associated with signifi cant obstructive coronary artery disease and high coronary artery calcium score.

A new model of arteriovenous fistula to study hemodialysis access complications.

This report presents a new animal model of arteriovenous fistula (AVF) with attention given to surgical techniques as well as hemodynamic and pathologic measurements. Of note, this model was created with a tunneled central catheter with the purpose of studying therapeutic interventions, including hemodialysis. Side-common carotid artery to end-external jugular vein AVFs were created in eight minipigs. A tunneled central catheter was also placed in the internal jugular vein. After 28 days, hemodynamic measurements of AVF flow and stenosis were performed. The minipigs were then euthanized and the AVFs were harvested for pathologic measurements of neointimal hyperplasia and thrombus volumes. In order to account for variable size of the AVFs, percentage luminal stenosis and degree of intima-media thickening were calculated. After 28 days, all eight AVFs remained patent. On average, 19% of arterial blood flow that approached the AVF traveled through the anastomosis. The average luminal stenosis by angiogram was 61.1%. The average neointimal hyperplasia and thrombus volumes were 1.4×10(8) and 3.8×10(8) μm3, respectively. The average luminal stenosis and intima-media thickening were 65.2% and 430.4 μm, respectively. This AVF model is ideal because of the relative ease of surgery and husbandry, lack of complications, as well as consistent and rapid development of the neointimal lesion which underlies AVF failure.

Histopathologic Characteristics of Atherosclerotic Coronary Disease and Implications of the Findings for the Invasive and Noninvasive Detection of Vulnerable Plaques

The goal of this study was to identify histomorphologic characteristics of atherosclerotic plaques and to determine the amenability of some of these components to be used as markers for invasive and noninvasive imaging. Rupture of the atherosclerotic plaques is responsible for the majority of acute coronary events, and the culprit lesions demonstrate distinct histopathologic features. It has been tacitly believed that plaque rupture (PR) is associated with angiographically minimally occlusive lesions. We obtained 295 coronary atherosclerotic plaques, including stable (fibroatheroma [FA]; n = 105), vulnerable (thin-cap fibroatheroma [TCFA]; n = 88), and disrupted plaques (plaque rupture [PR]; n = 102) from the hearts of 181 men and 32 women who had died suddenly. The hierarchical importance of fibrous cap thickness, percent luminal stenosis, macrophage area, necrotic core area, and calcified plaque area was evaluated by using recursive partitioning analysis. Because clinical assessment of fibrous cap thickness is not possible by noninvasive imaging, it was excluded from the second set of partitioning analysis. Thickness of the fibrous cap emerged as the best discriminator of plaque type; the cap thickness measured <55 μm in ruptured plaques, and all FA were associated with >84-μm cap thickness. Although the majority of TCFA were found in the 54- to 84-μm thickness group, those with <54-μm thickness were more likely to show <74% luminal stenosis (area under the curve: FA, 1.0; TCFA, 0.89; PR, 0.90). After exclusion of cap thickness, analysis of the plaque characteristics revealed macrophage infiltration and necrotic core to be the 2 best discriminators of plaque types (area under the curve: FA, 0.82; TCFA, 0.58; PR, 0.72). More than 75% cross-section area stenosis was seen in 70% of PR and 40% of TCFA; only 5% PR and 10% TCFA were <50% narrowed. This postmortem study defines histomorphologic characteristics of vulnerable plaques, which may help develop imaging strategies for identification of such plaques in patients at a high risk of sustaining acute coronary events.

Fractional Flow in Cerebrovascular Disorders

There is an urgent need for stroke experts to advance the care of their patients, yet current approaches are outmoded and have not been successful. The traditional emphasis on the anatomical identification of disease, using percent luminal stenosis, results in suboptimal identification of lesions likely to produce recurrent ischemia and, consequently, results in poor patient selection, and thus hampers the development of new aggressive treatments. The traditional emphasis on time since symptom onset and alleged need to achieve complete revascularization in patients with acute ischemic stroke ignores the very nature and degree of the underlying culprit lesion and hinders our understanding of the relationships between the patient’s original ischemic state, revascularization, reperfusion, reperfusion injury, and hemorrhagic transformation. The trajectory for the study and care of cerebrovascular patients needs to adapt, as it has in cardiology, employing hemodynamics and pathophysiology as the new guideposts for advancement. We introduce fractional flow as one hemodynamic parameter to be utilized to set a course on this new path for the care of stroke patients.

Abstract TP142: Prevalence of Cerebral Ischemic Events in Extraluminal Protruding Intracranial Atherosclerotic Plaques: Analysis of Intracranial Vessels from the Nun Study

INTRODUCTION: The prevalence and clinical significance of extraluminal protruding plaques in intracranial arteries is not fully understood. We aimed to identify the prevalence of ischemic events in persons with extraluminal protruding plaques in intracranial arteries. METHODS: A random sample of 100 subjects from Nun Study repository of post-mortem intracranial arteries was inspected. The study is a longitudinal study of aging and Alzheimer’s disease funded by the National Institute on Aging including 678 participants. A total of 61 subjects with visible atherosclerotic changes (defined as change in vessel wall color) were selected. The specimens were placed in a liquid container and an angiographic catheter was placed in vessel of interest. Angiography was obtained in multiple planes. Percentage luminal stenosis was measured using proximal or distal normal vessel as reference. Using microscopic images, extraluminal protruding plaques was then sequentially measured. RESULTS: Out of 61 subjects, 41 (67%) had angiographically detectable atherosclerotic plaques. Thirteen (13%) subjects had extraluminal protruding plaques and the remaining 7 (20%) subjects have neither angiographic stenosis nor extraluminal protruding plaques. Mean life expectancy was higher in patients with angiographic stenosis and outside plaque protrusion (59 and 51 versus 47 years). The prevalence of lacunar infarct, large infarct (&gt;1.5cm) in autopsy, and infarction identified in patient’s brain MRI were all higher in patients with extraluminal protruding plaques than patients without any plaque (38% versus 29%, 37% versus 31%, and 15% versus 14%, respectively). Mean serum cholesterol level was higher in patients with extraluminal protruding plaques (264 mg/dl versus 205 mg/dl). The prevalence of dementia in patients with angiographic stenosis, extraluminal protruding plaques, and no wall thickness change was 80%, 20%, and zero, respectively. CONCLUSIONS: Extraluminal protruding plaques without angiographic stenosis appear to be associated with ischemic events in patients. Higher prevalence of ischemic events in these patients warrants early detection using high resolution MRIand possible intervention.

Abstract 3829: Extraluminal Protruding Plaques in Intracranial Arteries. An angiographic and pathological analysis of Circle of Willis specimens from the Nun Study

BACKGROUND There is little data about extraluminal protruding plaques in intracranial arteries. Such plaques may not cause luminal stenosis and may be undetectable by standard angiographic modalities. It is important to identify the prevalence of such plaques because these plaques may be a cause of thrombosis and ischemic events in patients with cryptogenic strokes. OBJECTIVE To identify the prevalence of extraluminal protruding plaques in intracranial arteries from autopsy specimens of Nun Study. METHODS A random sample of 54 specimens was selected from Nun Study repository of post-mortem intracranial arteries (Circle of Willis). The Nun Study is a longitudinal study of aging and Alzheimer's disease funded by the National Institute on Aging including 678 participants who are 75 to 106 years of age. Basilar artery and proximal middle cerebral arteries were inspected and arteries with plaques were identified. The specimens were placed in a liquid container and an angiographic catheter was placed in vessel of interest. Using iodinated contrast media and Ziehm Vista C-arm, angiography was obtained in multiple planes. Percentage luminal stenosis was measured using normal proximal or distal segment of the vessel as reference. Using microscopic images, extraluminal protruding plaques was then sequentially measured. Percentage increase in extraluminal wall diameter was calculated as (extraluminal diameter at plaque site - normal diameter)/normal diameter x100. RESULTS Out of 162 samples, plaques were identified in 126 samples. The characteristics of the plaques are tabulated. The percentage increase in extraluminal wall diameter was 10.33 ± 8.13. For vessel with angiographically occult plaques, the percentage increase in extraluminal wall diameter was 9.2±3.2. In extraluminal protruding plaques, the median protrusion was 0.3 mm and maximum protrusion was 0.9 mm. There was no difference between the percentage extraluminal protrusion between the middle cerebral (0.3±0.1) and basilar artery plaques (0.36±0.2), p=0.8. The frequency of extraluminal plaques without angiographic stenosis of any severity was higher than extraluminal plaques with angiographic stenosis (52% and 56% for middle cerebral artery and basilar artery, respectively). CONCLUSIONS There appears to be a high prevalence of extraluminal protruding plaques among elderly persons and most of these plaques are not detected by angiography. Newer, imaging modalities like vessel wall high resolution visusalization by magnetic resonance imaging may help identify the prevalencc and ischemic event risk associated with such plaques.

Paclitaxel coating of the luminal surface of hemodialysis grafts with effective suppression of neointimal hyperplasia

Paclitaxel coating of hemodialysis grafts is effective in suppressing neointimal hyperplasia in the graft and vascular anastomosis sites. However, paclitaxel can have unwanted effects on the surrounding tissues. To reduce such problems, we developed a method to coat the drug only on the luminal surface of the graft, with little loading on the outer surface. A peristaltic pump and a double-solvent (water and acetone) system were used to achieve an inner coating of paclitaxel. At the ratio of 90% acetone, paclitaxel was homogeneously coated only on the luminal surface of the graft without changing the physical properties. To determine its effect, grafts were implanted between the common carotid artery and the external jugular vein in pigs using uncoated control grafts (n = 6) and low-dose (n = 6, 0.22 μg/mm(2)) and high-dose (n = 6, 0.69 μg/mm(2)) paclitaxel inner-coated grafts. Cross-sections of graft-venous anastomoses were analyzed histomorphometrically 6 weeks after placement to measure the patency rate, percentage of luminal stenosis, and neointimal area. No signs of infection or bacterial contamination were observed in the paclitaxel inner-coated groups. Only one of the six control grafts was patent, but all of the paclitaxel-coated grafts were patent, with little neointima. The mean ± standard error values of percentage luminal stenosis were 75.7% ± 12.7% (control), 17.5% ± 3.1% (low dose), and 19.7% ± 3.0% (high dose). The values for the neointimal area (in mm(2)) were 8.77 ± 1.66 (control), 3.53 ± 0.73 (lose dose), and 4.24 ± 0.99 (high dose). Compared with the control group, paclitaxel inner-coated vascular grafts significantly suppressed neointimal hyperplasia (low dose, P = .001; high dose, P = .002). Myofibroblast proliferation and migration into the graft interstices confirmed the firm attachment of the implanted graft to the surrounding tissue. Paclitaxel coating on the inner luminal surface of vascular grafts was effective in suppressing neointimal hyperplasia, with little inhibition of myofibroblast infiltration within the graft wall.

Clinical Outcome of Overlapping Stents in Hemodialysis Access

Endovascular stents have recently been shown to extend access patency in thrombosed and stenotic arteriovenous grafts. Given this improved patency, stent placement has outpaced balloon angioplasty in hemodialysis (HD) access interventions. However, concern remains over localized corrosion and increased neointimal hyperplasia of overlapping stents in the access circuit and whether this promotes premature stent failure. This is a retrospective analysis of HD patients referred for access dysfunction during a 2-yr period. Using a prospectively collected, vascular access database, we identified 76 patients seen for follow-up angiography due to access dysfunction after stent placement. We compared the outcomes of overlapping vs. non-overlapping stents in measured primary assisted patency and mean percent luminal diameter as a marker of lesion severity. The two groups did not differ significantly in demographics or comorbid conditions. Only gender had a significant discrepancy between the two groups, with 65.5% vs.42.9% male (p=0.01) in the overlapping vs. non-overlapping stent groups, respectively. The mean percent luminal stenosis was found to be 83.7 ± 17.3 and 85.5 ± 12.6 (p=0.55) for the overlapping vs. non-overlapping stent groups, respectively. For overlapping and non-overlapping stents, 30-day primary patency was 94% and 89%, respectively, 60-day primary patency was 77% and 63%, respectively, and 90-day primary patency was 68% and 50%, respectively. Using multiple regression analysis, no risk factors were identified to be associated with the severity of luminal stenosis. No identifiable risk factors were found to be associated with improved primary patency. In particular, overlapping vs. non-overlapping stents were not identified as a statistically significant factor influencing primary (assisted) patency (hazards ratio 0.60; 95% CI 0.34 to 1.06; p>0.05). This study provides evidence that the theoretical concern of metal on metal corrosion and increased neointimal hyperplasia that can be seen with overlapping stents does not play a significant clinical role.

Enhanced atherothrombotic formation after oxidative injury by FeCl 3 to the common carotid artery in severe combined hyperlipidemic mice

Enhanced susceptibility to atherosclerosis from severe hypertriglyceridemia (HTG) resulting from lipoprotein lipase (LPL) deficiency has been demonstrated in our recent findings which employed a unique mouse model. In the present study we provide further evidence that severe HTG due to LPL deficiency also promotes an atherothrombotic response to arterial injury induced by ferric chloride in a severe combined hyperlipidemic mouse model. Methods and results: A mouse model (LPL −/−XApoE −/− double knockout, DKO) with severe combined hyperlipidemia was established by crossing ApoE and LPL-deficient mice. The common carotid arteries of ApoE knockout (EKO) and DKO mice were subjected to injury by ferric chloride, and the formation of arterial thrombosis together with various markers were compared in these lesions. DKO mice demonstrated significantly enhanced thrombus formation overlying atherosclerotic plaque after injury, which contained smooth muscle cells, macrophages, and neutral lipid. The area of neointima, mean intima/media ratios, and the percentage of luminal stenosis were significantly greater ( P < 0.01) in DKO mice. Compared with EKO mice, the expression of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1) were increased in DKO mice. Conclusions: Severe combined hyperlipidemia promotes thrombosis after ferric chloride injury to atherosclerotic vessels and HTG plays a major role in the process.

The Effects of Toradol on Postoperative Intimal Hyperplasia in a Rat Carotid Endarterectomy Model: Laboratory Research

Carotid endarterectomy (CEA) and more recently carotid artery stenting are the treatments of choice for atherosclerotic disease of the extracranial carotid arteries; however, early restenosis caused by neointimal hyperplasia confounds surgical therapy. Oxidative stress has been implicated in the progression of intimal hyperplasia. The authors hypothesized that ketorolac tromethamine (Toradol), a nonsteroidal antiinflammatory drug that is a potent cyclooxygenase inhibitor, would decrease oxidative stress and thereby reduce intimal hyperplasia in a rat CEA model. Twenty-nine male Sprague-Dawley rats underwent CEA and were divided into 3 treatment groups as follows: (1) control (placebo), (2) 7.5 mg/kg Toradol, and (3) 10 mg/kg Toradol. Toradol treatment began 2 days before CEA and continued for 2 weeks. Two weeks after endarterectomy, carotid arteries were fixed, harvested, and examined for platelet activity (platelet reactive units), oxidative stress (malondialdehyde and glutathione), and intimal hyperplasia (measured as percentage of luminal stenosis). Platelet activity, malondialdehyde and glutathione, and intimal hyperplasia were all significantly lowered in both 7.5- and 10-mg/kg doses of Toradol versus control. Toradol given daily beginning 2 days before CEA and ending 2 weeks after the procedure was effective at significantly reducing platelet activity, oxidative stress, and intimal hyperplasia development in the rat without any increase in bleeding. Although the mechanism of action of this reduction is not completely understood, one possible explanation may be through the inhibition of reactive oxygen species production.