Yukiko Enomoto

Prediction of silent ischemic lesions after carotid artery stenting using integrated backscatter ultrasound and magnetic resonance imaging

OBJECTIVE A major concern with carotid artery stenting (CAS) is the potential for cerebral embolism. The purpose of this study was to determine whether integrated backscatter (IBS) ultrasound and black-blood magnetic resonance imaging (BB-MRI) can predict the risk of a silent ischemic lesion after CAS. METHODS We performed quantitative analysis of plaque characteristics in carotid arteries using IBS ultrasound and BB-MRI before CAS in 50 patients. We measured IBS values and the signal intensity ratio (SIR) from T1 weighted images of all plaques. We also performed diffusion-weighted (DWI) MRI of the brain before and after CAS. RESULTS In the patient group that was positive (n=19) for newly appearing ipsilateral silent ischemic lesions (NISIL), relative unstable component area (%UCA) evaluated by IBS analysis (60.2+/-23.4% and 35.3+/-19.2%, p<0.001) and SIR (1.40+/-0.19 and 1.18+/-0.25, p<0.01) in most stenotic lesions were higher than in the NISIL-negative group (n=31). From the analysis of receiver operating characteristic curves, 50% of the %UCA measured by IBS and an SIR of 1.25 measured by BB-MRI were the most reliable cutoff values for predicting NISIL. In multivariate logistic regression analysis, the independent predictors of NISIL were SIR (p=0.030), the CRP level (p=0.041) and the %UCA measured by IBS (p=0.049). CONCLUSIONS Quantitative tissue characterization of carotid plaques using IBS ultrasound and BB-MRI was useful to predict NISIL after CAS. The plaque components in carotid arteries should be evaluated by BB-MRI or IBS ultrasound before CAS to improve the clinical outcome of this procedure.

Staged angioplasty for carotid artery stenosis to prevent postoperative hyperperfusion.

OBJECTIVE Hyperperfusion (HP) is a rare but potentially devastating complication after carotid revascularization. This report describes the clinical efficacy of staged angioplasty (SAP) for carotid artery stenosis to prevent HP after carotid revascularization. METHODS Eighteen of 143 patients with high-grade internal carotid artery stenosis scheduled for angioplasty were considered at high risk of postprocedure HP based on their severely impaired cerebral blood flow (CBF) and cerebral vasoreactivity, which were determined using single-photon emission computed tomography with acetazolamide. Nine of the high-risk patients were treated with carotid artery stenting and the other 9 were treated with SAP, which consisted of balloon angioplasty with undersized balloon catheters (Stage 1) followed by carotid artery stenting 1 to 2 months later (Stage 2). RESULTS In the regular carotid artery stenting group, 5 of 9 patients (56%) showed HP phenomenon on single-photon emission computed tomography just after stenting, and 1 patient (11%) developed status epilepticus owing to HP. In the SAP group, none of the 8 patients treated by SAP or the 1 patient who required stent placement during the first stage owing to a wall dissection developed postprocedure HP phenomenon or HP syndrome. CONCLUSION SAP decreased the HP phenomenon on single-photon emission computed tomography after performing these procedures in selected patients. Although additional intervention is needed, SAP is considered a relatively simple and effective method to avoid HP in patients at high risk of HP after carotid revascularization.

Visualization of internal carotid artery atherosclerotic plaques in symptomatic and asymptomatic patients: a comparison of optical coherence tomography and intravascular ultrasound.

BACKGROUND AND PURPOSE: OCT has been reported as a high-resolution imaging tool for characterizing plaque in the coronary arteries. The present study aimed to evaluate the ability of OCT to visualize carotid artery plaques compared with that of IVUS in asymptomatic and symptomatic patients. MATERIALS AND METHODS: OCT was performed for 34 plaques (17 symptomatic, 17 asymptomatic) in 30 patients during CAS under a proximal cerebral protection method. OCT was performed before balloon angioplasty and after stent placement. IVUS was also performed just after OCT. RESULTS: No technical or neurologic complications were encountered by using OCT. An inner catheter was used in 12 of 34 procedures (35.3%) for advancing the OCT image wire beyond the site of stenosis. OCT clearly visualized intraluminal thrombus in 15 of 34 plaques (44.1%), whereas IVUS detected a thrombus in 1 plaque (2.9%, P < .001). Neovascularization was demonstrated in 13 of 34 plaques (38.2%) by OCT, but not by IVUS (0%, P < .001). Intraluminal thrombus was more frequently observed in symptomatic plaques (13 of 17, 76.5%) than in asymptomatic plaques (2 of 17, 11.8%; P < .001). Interobserver and intraobserver variability with OCT diagnosis was excellent for thrombus, ulceration, neovascularization, and lipid pool. CONCLUSIONS: The present findings suggest that OCT can safely and precisely visualize human carotid plaques during CAS and that intraluminal thrombus and neovascularization are more frequently detected in symptomatic plaques.

Effects of Atorvastatin on Carotid Atherosclerotic Plaques: A Randomized Trial for Quantitative Tissue Characterization of Carotid Atherosclerotic Plaques with Integrated Backscatter Ultrasound

Background: Instability of carotid plaques has been reported to be associated with stroke and other cerebrovascular events. The purpose of this study was to examine whether cholesterol-lowering therapy with atorvastatin in nonhypercholesterolemic patients reduces carotid plaque instability as assessed by ultrasound integrated backscatter (IBS) analysis. Methods: Consecutive non- or slightly hypercholesterolemic patients with moderate carotid artery stenosis were randomly assigned to a diet group (n = 20) or a statin group (atorvastatin; n = 20). Carotid plaques were monitored by measuring intima media thickness (IMT) and IBS values at baseline and after 6 months. Results: Three-dimensional IBS imaging showed that relative lipid volume of carotid plaques significantly decreased from 58.4 ± 25.6 to 47.8 ± 23.5% in the statin group (p < 0.01), whereas there was no significant decrease in the diet group. Significant regression of IMT was not observed in either group. The changes of IBS values and relative lipid volume between baseline and 6 months were correlated with the change in low-density lipoprotein cholesterol (r = 0.31, p < 0.05, and r = 0.34, p < 0.05, respectively). Conclusions: Lipid-lowering therapy by atorvastatin decreased relative lipid volume without significant regression of plaque volume during short-term follow-up in patients with moderate carotid artery stenosis. Quantitative assessment of carotid plaques by IBS analysis was clinically useful for monitoring atherosclerotic lesions.

Thromboxane A2 promotes soluble CD40 ligand release from human platelets

OBJECTIVE The plasma level of soluble CD40 ligand (sCD40L), which induces pro-inflammatory and pro-atherogenic responses, is known to be elevated in atherosclerotic patients. In this study, we investigated the mechanism of sCD40L release from human platelets, focusing on the involvement of thromboxane (TX) A(2). METHODS We measured sCD40L release and TXA(2) production induced by ristocetin, an activator of GPIb/IX/V, from human platelets in vitro. Moreover, plasma sCD40L and TXA(2) levels in the 10 patients with severe carotid artery stenosis who were not taking any anti-platelet medicines were measured and compared with those obtained from non-atherosclerotic controls. RESULTS Ristocetin significantly promoted sCD40L release and TXA(2) generation from platelets in vitro. Aspirin and SC-560, a cyclooxygenase-1 inhibitor, suppressed the ristocetin-induced sCD40L release from platelets in parallel with TXA(2) production. Ozagrel, a TXA(2) synthase inhibitor and PTXA(2), a thromboxane receptor (TP) antagonist also suppressed sCD40L release. U46619, a TP agonist, reversed the suppressive effect of aspirin on sCD40L release. In vivo, plasma levels of sCD40L and TXA(2) in the patients were significantly higher than those in controls. Elevated plasma levels of TXA(2) and sCD40L in the patients were markedly diminished after 7 days of 100mg aspirin administration. CONCLUSION These results strongly suggest that GPIb/IX/V activation induces sCD40L release via TXA(2) from human platelets, and that sCD40L release via TXA(2) generation from platelets in atherosclerotic patients are up-regulated.

αB‐crystallin extracellularly suppresses ADP‐induced granule secretion from human platelets

αB‐crystallin, a low‐molecular‐weight heat shock protein (HSP), has binding sites on platelets. However, the exact role of αB‐crystallin is not clarified. In this study, we investigated the effect of αB‐crystallin on platelet granule secretion. αB‐crystallin attenuated the adenosine diphosphate (ADP)‐induced phosphorylation of p44/p42 mitogen‐activated protein kinase (MAPK) and p38 MAPK. The ADP‐stimulated HSP27 phosphorylation was markedly reduced by αB‐crystallin. αB‐crystallin significantly suppressed the ADP‐induced secretions of both platelet‐derived growth factor (PDGF)‐AB and serotonin. Therefore, our results strongly suggest that αB‐crystallin extracellularly suppresses platelet granule secretion by inhibition of HSP27 phosphorylation via p44/p42 MAPK and p38 MAPK.

Current perioperative management of anticoagulant and antiplatelet use in neuroendovascular therapy: analysis of JR-NET1 and 2.

To evaluate current perioperative antithrombotic management in neuroendovascular therapy in Japan, we analyzed perioperative anticoagulant and antiplatelet use in various procedures and examined their relationships with periprocedural adverse events. Patients data from nationwide surveys administered by the Japanese Registry of Neuroendovascular Therapy (JR-NET) between January 2005 and December 2007 (JR-NET1) and January 2008 and December 2009 (JR-NET2) were retrospectively analyzed. Compared to JR-NET1, the frequency of perioperative antiplatelet therapy and dual or triple therapy were increased for either aneurysm coiling and percutaneous transluminal angioplasty or stenting in JR-NET2. Although ischemic complications were significantly decreased (4.2% vs. 2.1%, p < 0.001), hemorrhagic complications (2.1% vs. 5.3%, p < 0.001), severe adverse events (1.5% vs. 2.1%, p < 0.001), and total perioperative complications (8.3% vs. 10.3%, p < 0.001) were significantly increased in JR-NET2. The rate of hemorrhagic complications was significantly higher in patients with triple or more perioperative antiplatelet therapy (preoperative: 5.3% vs. 9.2%, p < 0.0001, postoperative: 5.7% vs. 12.7%, p < 0.0001). Perioperative antithrombotic therapy was performed more frequently and intensively in neuroendovascular therapy in Japan. While ischemic complications were decreased, hemorrhagic complications and severe adverse events were increased. These results suggest that intensive antithrombotic therapy has a potential risk of hemorrhagic complications for Japanese patients.

Mechanism of collagen-induced release of 5-HT, PDGF-AB and sCD40L from human platelets: Role of HSP27 phosphorylation via p44/p42 MAPK

Collagen plays a crucial role in hemostasis and thrombosis by activating platelets and reportedly induces the phosphorylation of heat shock protein (HSP) 27 in human platelets. However, the exact role of HSP27 phosphorylation in human platelets has not yet been clarified. In the present study, we investigated the mechanism of collagen-induced HSP27 phosphorylation and the role in human platelets. The collagen-effect on the phospholylation of HSP27 was dose-dependent in the range between 0.03 and 1.0 microg/ml. The phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK) was also stimulated by collagen. PD98059, a specific inhibitor of MAPK kinase (MEK1/2), reduced collagen-induced HSP27 phosphorylation as well as p44/p42 MAPK phosphorylation. PD98059 significantly suppressed collagen-induced releases of serotonin (5-HT), platelet-derived growth factor (PDGF)-AB and soluble CD40 ligand (sCD40L) while it had little effect on the platelet aggregation. These results strongly suggest that the collagen-induced phosphorylation of HSP27 via p44/p42 MAPK is sufficient for releases of 5-HT, PDGF-AB and sCD40L from human platelets.

Morphologic Features of Carotid Plaque Rupture Assessed by Optical Coherence Tomography

BACKGROUND AND PURPOSE: Rupture of the plaque fibrous cap and subsequent thrombosis are the major causes of stroke. This study evaluated morphologic features of plaque rupture in the carotid artery by using optical coherence tomography in vivo. MATERIALS AND METHODS: Thirty-six carotid plaques with high-grade stenosis were prospectively imaged by optical coherence tomography. “Plaque rupture” was defined as a plaque containing a cavity that had overlying residual fibrous caps. The fibrous cap thickness was measured at its thinnest part for both ruptured and nonruptured plaques. The distance between the minimum fibrous cap thickness site and the bifurcation point was also measured. Optical coherence tomography identified 24 ruptured and 12 nonruptured plaques. RESULTS: Multiple ruptures were observed in 9 (38%) patients: Six patients had 2 ruptures in the same plaque, 2 patients had 3 ruptures in the same plaque, and 1 patient had 5 ruptures in the same plaque. Most (84%) of the fibrous cap disruptions were identified at the plaque shoulder and near the bifurcation point (within a 4.2-mm distance). The median thinnest cap thickness was 80 μm (interquartile range, 70–100 μm), and 95% of ruptured plaques had fibrous caps of <130 μm. Receiver operating characteristic analysis revealed that a fibrous cap thickness of <130 μm was the critical threshold value for plaque rupture in the carotid artery. CONCLUSIONS: Plaque rupture was common in high-grade stenosis and was located at the shoulder of the carotid plaque close to the bifurcation. A cap thickness of <130 μm was the threshold for plaque rupture in the carotid artery.

Prediction of Silent Ischemic Lesions after Carotid Artery Stenting Using Virtual Histology Intravascular Ultrasound

Background: A major concern with carotid artery stenting (CAS) is the potential for cerebral embolism. The purpose of this study was to determine whether virtual histology intravascular ultrasound (VH-IVUS) can predict the risk of a silent ischemic lesion after CAS. Methods: We performed CAS in 45 patients with carotid stenosis. Before CAS, we assessed plaque characteristics by VH-IVUS. We also performed diffusion-weighted magnetic resonance imaging of the brain before and after CAS to detect newly appearing ipsilateral silent ischemic lesions (NISIL). Results: In the patient group that was positive for NISIL (P group: n = 18), the relative fibrofatty (FF) area identified by VH-IVUS in 5 cross-sections including the most stenotic lesion was significantly larger than that in areas of the NISIL-negative group (N group: n = 27; 32.7 ± 13.2 and 18.3 ± 9.8%, respectively; p < 0.001). The relative fibrous area was significantly lower in the P group than in the N group (59.2 ± 9.5 and 74.6 ± 9.1%, respectively; p < 0.001). There were no differences in the relative dense calcium and necrotic core areas between the P and N groups. From the analysis of receiver operating characteristic curves, most reliable cutoff values for predicting NISIL were a relative FF area of 30% in the most stenotic lesion. In multivariate logistic regression analysis, the relative FF area was an independent predictor of NISIL (p = 0.005). Conclusions: Quantitative tissue characterization of atherosclerotic lesions of carotid arteries using VH-IVUS was useful to predict NISIL after CAS. However, the positive predictive value determined by VH-IVUS was not superior to that determined by a noninvasive method.