AHA Type Research Articles

MPO activity determined by molecular MRI is associated with ruptured and destabilised human atherosclerotic plaques

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): National Health & Medical Research Council - Postgraduate Scholarship National Heart Foundation - PhD Scholarship University of New South Wales - RTP Scholarship Introduction Intraplaque MPO activity is associated with unstable atherosclerosis and elevated following acute cardiovascular events. Imaging probes for the detection of MPO exist, including MPO-Gd, a gadolinium-based probe activated and retained in the presence of MPO-specific chlorinating species. To date, the utility of MPO activity in plaque rupture has not been examined. We sought to assess the association between intraplaque MPO activity and ruptured human plaques. Method Carotid endarterectomy specimens (CEA) were collected from 30 patients undergoing surgery. Following pre-surgical in vivo MRI for plaque characterisation, ex vivo plaques were activated using MPO-Gd. MPO-Gd retention was then correlated to AHA plaque grading both histologically and by in vivo MRI as well as liquid chromatography mass spectrometry (LC-MS/MS) through the addition of hydroethidine tissue sections and it’s conversion to the MPO-specific adduct 2-chloroethidium (2-Cl-E+). Results MPO-Gd retention in CEA was greater in both histologically and MRI-graded ruptured and destabilised AHA type VI plaques compared to types III-V (T1 percentage recovery from baseline: VI: 52% ± 5.7 vs. V: 77% ± 7.8, IV: 83% ± 8.2 and III: 84% ± 6.8; p < 0.0001). This association was confirmed by comparing histological AHA grade to MPO activity determined by LC-MS/MS (2-Cl-E+ corrected to internal standard per mgp: VI: 0.2 ± 0.2 vs. V: 0.00 ± 0.01, IV: 0.01 ± 0.01, and III: 0.03 ± 0.03; p = 0.005). Discussion We demonstrate that MPO activity determined by MPO-Gd and compared to histology is increased in ruptured human plaques. These results highlight the unique and specific role of intraplaque MPO activity and its potential application as a molecular probe in the detection of vulnerable atherosclerosis.

Treatment of In-Stent Restenosis Using a Dedicated Super High-Pressure Balloon

BackgroundTreatment of in-stent restenosis (ISR) is challenging and treatment failure rate remains high. Correction of stent under-expansion and neointimal compression using the twin-layer OPN™ highly non-compliant balloon (NCB) at high pressure (>30 atm) may lead to increased luminal gain and thus better clinical outcomes. We evaluated periprocedural safety and clinical long-term outcomes after ISR treatment using the OPN™ NCB in a real-world population. MethodsFrom an ongoing registry, consecutive ISR patients treated with the OPN™ NCB at a tertiary cardiology center in Switzerland were analyzed. We evaluated procedural efficacy, periprocedural complications, target lesion/vessel failure (TLF/TVF), and major adverse cardiovascular events (MACE). ResultsTotally, 208 ISR lesions were treated in 188 patients (mean age 68 ± 13 years, 78 % males). Most lesions were moderately to heavily calcified (89 %), the majority (70.2 %) had complex lesion characteristics (AHA Type B2/C lesions) and 50.5 % were non-focal ISR lesions. After ISR treatment using high pressure pre- and post-dilatation (mean pressure 33 ± 6 atm) with the OPN™ NCB device, the rate of major complications was low (0.96 % coronary perforation, 4 % major dissections, 1.9 % no-reflow and 0.5 % acute vessel closure). At 1-year follow-up, MACE occurred in 19.7 %; 15.4 % patients had TVF; MI and stent thrombosis was found in 5.9 % and 2.1 % of all patients, respectively; and 5 patients died. ConclusionsFor ISR treatment, using the super non-compliant OPN™ balloon at very high pressures is safe. Moreover, its use might lead to a low rate of TLF/TVF during long-term follow-up, but this requires further evaluation in dedicated comparative trials.

Haemodynamic analysis using multiphase flow dynamics in tubular lesions

Background and Objective: The role of red blood cell dynamics is emphasised in certain cardiovascular diseases, and thus needs to be closely studied. A multiphase model of blood flow allows the resolution of locally varying density of red blood cells within a complex vessel geometrical domain, and haemodynamic consequences of such build up.Methods: A novel computational fluid dynamics solver for simulating multiphase flows is used for modelling blood flow using level set for a sharp interface representation. Single-phase simulations and reduced order models are used for pressure comparisons. The new solver is used for numerically studying AHA type B lesions. The impact of hematocrit and degree of stenosis on the haemodynamics of coronary arteries is investigated.Results: The comparisons with single-phase flow simulations indicate differences in pressure when considering red blood cell aggregation. Multiphase simulations provide slightly lower pressure drop for the same stenosis severity compared to the single-phase simulations. Secondary flow patterns and the interactions between the two phases leads to the red blood cell aggregation at the end of the diastole cycle, which significantly changes the red blood cell distribution, the shear stresses and velocity in tubular lesions.Conclusions: Neither pressure drop nor mean velocity are not strongly changed in the multiphase modelling, but particle buildup significantly changes which is only revealed by the multiphase approach.

Abstract 17028: Single Cell Analysis of T Cells Found in Atherosclerotic Plaque

Background: Despite advances in medical therapy, heart attack and stroke remain leading causes of morbidity and mortality. Biological, epidemiological, and clinical studies have shown that many patients (up to 33% in some trials) still have residual inflammatory risk that is associated with plaque rupture, even in the setting of low LDL. Methods and Results: In this study, we analyzed the T cell landscape of coronary atherosclerotic plaque to determine their role in the development of atherosclerosis and its adverse sequelae. We recruited 17 patients undergoing heart transplantation. From each explanted heart, we obtained plaques from the major coronary arteries, digested them to form a single cell suspension, sorted the arteries for CD4 and CD8 T cells into 96 well plates, and submitted them for single cell genotyping and phenotyping ( Figure 1 ). Although peripheral blood from these patients also contains T cell clones, plaque CD8 T cell clones appear to function differently than blood (e.g., producing more BCL6, TNF-, and interferon gamma) further supporting that this is not a bystander effect. We found CD4 and CD8 T cells with identical TCR sequence across the arteries of the same patient, suggesting CD8T cells are purposely recruited to the plaques. When we analyzed the percent clonality based upon location and disease severity, we find that clonality is not dependent on location and is present at all severity levels, especially, in early disease (e.g., AHA Type I-IV lesions. Conclusion: CD8 T cells are clonally expanded in atherosclerotic plaque and appear to function differently than blood, suggesting these cells are purposefully recruited.

910 Uptake and Utilisation of Intravascular Imaging to Guide Percutaneous Coronary Intervention: Insights from the Victorian Cardiac Outcomes Registry

Percutaneous coronary intervention (PCI) remains an established therapeutic option for myocardial revascularisation. Use of intravascular imaging to guide PCI is known to improve clinical outcomes, with this benefit most pronounced when tackling complex lesion subsets. We therefore sought to ascertain the current uptake and use of intravascular imaging based on anonymised data from the Victorian Cardiac Outcomes Registry (VCOR). All consecutive patients undergoing PCI for coronary artery disease (CAD) were included (n=51,044) from January 2013 through December 2018. Intravascular imaging included intravascular ultrasound (IVUS) and optical coherence tomography (OCT) use. Patient/lesion characteristics were obtained and compared between angiographic- and imaging-PCI guided groups. Overall, 873 (1.7%) of patients had intravascular imaging to guide PCI during the study period, with IVUS used in 602 (1.2%), OCT in 246 (0.48%) and both in 25 (0.05%) cases. There was an increase in case rates of intravascular imaging year on year (p=0.001). Intravascular imaging was more commonly used in patients with diabetes (p=0.04) and those with stable CAD (p<0.001). Although angiographically-guided PCI remained the default modality used for treatment of all complex lesion subsets, rates of intravascular imaging use were higher for left-main stem intervention (14.7%), stent thrombosis (9.4%), in-stent restenosis (4.6%), treatment of chronic total occlusions (3.0%) and AHA Type B2/C lesions (1.9%). The uptake of intravascular imaging use during PCI remains limited in Victoria, even when considering more complex PCI procedures. These data should renew our focus on education, reimbursement and support for using intravascular imaging in Australia.

Angiographic Analysis of Trans-Radial Percutaneous Coronary Intervention Cases by the Backup Support of Guide Extension Catheter

Background:The guide extension catheter – Guidezilla (Boston Scientific, United States of America) is a useful adjunctive tool in percutaneous revascularization of complex coronary lesions, and provides an extension to the guide catheter with better coaxial alignment, support and stability.Objective: The objective of this study was to describe the usefulness and easy deliverability of stent by Guidezillain the trans-radial treatment of complex coronary lesions as our initial experience.Methods:This prospective observational study was conducted at the Department of Cardiology, Ibrahim Cardiac Hospital &amp; Research Institute (ICHRI), Dhaka from July 2016 to September 2017. The transradial approach was used in all cases. Clinical, angiographic and procedural data of percutaneous coronary interventions performed using Guidezilla, including indications for use of Guidezilla were collected and analyzed.Results:A total of 19 procedures (in 18 patients) were evaluated. 57.89% of cases were related to left circumflex coronary artery or obtuse marginal branch. The commonest challenge for use of Guidezillawas proximal angulation (63.15%) and calcification (47.4%). Commonest type of lesion was ACC/ AHA Type C lesion (63.2%). Successful stent deployment was achieved in 16 of the 19 procedures (84.2%). Among the unsuccessful cases, there was stent damage in one case and distal dissection after deployment of a stent in other. Stent deployment was not possible in two cases, due to diffuse lesion and heavy calcification.Conclusions:Guide extension catheter is a good trans-radial back-up support for calcified, complex and tortuous coronary anatomy, which otherwise may have been considered unsuitable for PCI. The use of such support can reduce the necessity for the more expensive alternative of deploying multiple small stents in order to traverse the lesions.Bangladesh Heart Journal 2018; 33(1) : 54-60

Neovascularization in Advanced Atherosclerosis - A Histomorphometric Study

Introduction: Neovascularization is an important component of ad vanced atherosclerosis which leads to plaque vulnerability and rupture. This is an endarterectom y study where neovascularization is quantified in 5 0 advanced atherosclerotic plaques by using IHC stain and meas uring the positivity by histomorphometry, simultane ously assessing lipid pool area and fibrous cap thickness (average and minimum), also by histomorphometry. The values were compared across different AHA types and also probable vulner able plaques were identified. Materials & Methods: Three heart specimens obtained at autopsy from subjects who died of RTA showed evidence of coronary artery disease on post- mortem coronary angiogram. Coronary endarterectomy was done from these specimens and was made into tissue blocks for histological study. On H& E sections the plaque s were classified by AHA typing and 50 advanced atherosclerotic plaques were chosen for this study. To assess neova scularization, the IHC stain CD34 was used and the percentage area of positivity was later measured using histomorphometry. The lipid pool area in the plaques and the fi brous cap thickness were also measured using histomorphometry. Results: In our study, 47 out of 50 advanced lesions showed neovascularization although the difference in their amounts between AHA Type IV and V was not statistically significant. On measuring lipid pool area and fibro us cap thickness, we found 4 of the 50 plaques to b e probable vulnerable plaques as they had a combination of a l arge lipid pool (>40% of the plaque area) and a thi n fibrous cap (<65 μ) in addition to revascularization. Conclusion: This study showed that neovascularization was seen in most of the advanced atherosclerotic plaques and together with some other features like large lipid pool and thin fibrous cap, it can potentially make a plaque vulnerable to rupture. Th e understanding of role of neovascularization in pl aque rupture has led to the trial of antiangiogenic therapy to preve nt plaque progression.

Quantification of Various Inflammatory Cells in Advanced Atherosclerotic Plaques.

Atherosclerosis, the pathological basis of coronary artery disease is being extensively studied as understanding of the complex processes involved in the formation and progression that can provide an insight into prevention and treatment of the same. This is an autopsy study to identify and quantify various inflammatory cells in advanced atherosclerotic plaques. This study aims at identifying and categorizing the various inflammatory cells present in advanced atherosclerotic plaques, noting their distribution in the plaque, quantifying them using histomorphometry and comparing them across plaques of different AHA types. Post-mortem angiogram was performed on 3 heart specimens obtained at autopsy of random Road Traffic Accident (RTA) cases which revealed evidence of coronary artery disease. End-arterectomy was done and the arteries with atherosclerotic plaques were cut into serial sections and made into tissue blocks. Sections from these blocks were stained with H & E stain and the plaques were classified based on AHA classification. 50 advanced atherosclerotic plaques of AHA Type IV and V were chosen for this study and were screened for inflammatory cells, first with H & E stain and then with different immunohistochemical stains for T-lymphocytes, B-lymphocytes and neutrophils. The T-lymphocytes thus identified was further sub-typed into CD4+ and CD8+ cells again using IHC markers and the percentage area of each was measured using histomorphometry. Then, these values were compared between AHA Type IV and AHA Type V lesions. It was found that the inflammatory cells found in advanced atherosclerotic plaques were predominantly T-lymphocytes as evidenced by their CD3 positivity and they were found to be distributed mainly around the shoulder region and fibrous cap of the plaque. When categorized further, it was found that CD8+ T-cells were always more than CD4+ T-cells in advanced lesions. Meloperoxidase stain for neutrophils was negative in all the plaques examined. The difference in the amount of inflammatory cells between AHA type IV and Type V was not statistically significant. The study of the amount of inflammatory cells in atherosclerotic plaques and understanding their role in the pathophysiology of advanced plaques may have therapeutic implications.

Feasibility of second-generation bioresorbable vascular scaffold implantation in complex anatomical and clinical scenarios.

BackgroundBioresorbable vascular scaffolds (BVS) have become an emerging tool to treat coronary artery disease. However, the current use of BVS is still widely restricted to stable patients and non-complex lesions. In real-world practice patients are far more complex than those with simple type A lesions and the extended use of BVS to complex lesions and high-risk patients needs to be evaluated. Therefore, we sought to investigate the feasibility and performance of BVS in a broad spectrum of patients.Methods106 patients underwent in total 193 BVS implantations. We assessed the device-related (cardiac death, target vessel myocardial infarction, ischemia-driven target lesion revascularization) and patient-related (all-cause death, any reinfarction and any revascularization) composite outcomes.Results90 % of patients (n = 95) had at least one of the following characteristics: >65 years (35 %), ACS (42 %), tortuous vessels (13 %), calcified (17 %) or thrombotic lesions (12 %), lesions defined as AHA type B2/C (42 %), bifurcations (16 %), chronic total occlusions (9 %) or restenosis (14 %). There was no evidence of significant edge dissection, huge thrombus load or incidence of scaffold dislodgement or scaffold disruption in optical coherence tomography pullbacks. Out of 10,157 struts evaluated within 1,117 cross-sections, 302 were classified as malapposed (2.9 %). During a mean follow-up of 147 ± 119 days the rate of device-related events was 2.0 %, whereas patient-related composite events occurred in 6.1 %.ConclusionsOur results strongly suggest that BVS implantation is feasible in a wide spectrum of patients and complex anatomy of coronary lesions. Long-term outcome of BVS should be further investigated in unrestricted settings in randomized controlled trials.Electronic supplementary materialThe online version of this article (doi:10.1007/s00392-014-0757-4) contains supplementary material, which is available to authorized users.

Clinical outcomes with 6 months dual antiplatelet therapy after implantation of Biolimus-A9 drug eluting coronary stents

IntroductionDuration of dual antiplatelet therapy (DAPT) following drug eluting stent (DES) implantation remains poorly defined. Endothelialisation of biodegradable polymer biolimus-eluting stents occurs early, and 6 months DAPT may be adequate. AimsWe evaluated long term outcome in patients treated with biolimus-eluting stents who were treated with 6 months DAPT. Endpoints included cardiac death and non-fatal stent thrombosis occurring 6 to 12 months after stent implantation. Methods692 patients (77.2% male), aged 65.6±12.5years received biolimus-eluting DES (March 2008 –November 2011). Vital status was tracked through the Medical Research Information Service. Episodes of non-fatal stent thrombosis, (Academic Research Consortium definition) between months 6 and 12 were tracked via systematic database searches (5 PCI centres). ResultsPresentations included acute coronary syndrome (47.2%) and stable coronary disease (52.8%). Vessels treated included left main stem (6.8%), left anterior descending (37.4%), circumflex (19.1%), right coronary artery (34.5%) and saphenous vein graft (2.1%) respectively. High-risk subsets included diabetes (15.6%); AHA type C lesions (35.1%) and chronic total occlusions (12.8%). During median follow-up of 700 days (0 to 1392) there were 42 deaths (6.1%); 4.2% at 0–6months, 1.0% at 6–12months and 0.9% at >12months. Of the 7 deaths between 6 and 12months, one death was adjudicated as possible stent thrombosis. There were no cases of non-fatal known stent thrombosis. All cause mortality accrued with smooth decremental incidence. Statistical examination showed no evidence of event clustering between 6 and 12 months. ConclusionsAfter implantation of biodegradable polymer biolimus-eluting coronary stents, 6 months DAPT appears to be adequate, safe and effective.

PERIPROCEDURAL MYOCARDIAL NECROSIS PREDICTION BY SYNATX SCORE DURING PERCUTANOUS CORONARY INTERVENTION IN DIABETIC PATIENTS

Background: Peri-procedural myocardial injury (PPI) during percutaneous coronary intervention (PCI) is common and associated with a poor outcome. No reliable angiographic or clinical predictors of PPI exist. We evaluated the ability of the SYNTAX score (SXscore), Gensini score and American Heart Association/American College of Cardiology (AHA/ACC) classification to predict PPI. Methods: 60 patients with chronic stable angina not controlled by medical treatment were included from the day case PCI. Inclusion criteria; patients undergoing insertion of 2.0 mm in diameter, and/or patients undergoing double vessel PCI. Exclusion criteria; Patients with heart failure and lesions > 30 mm in length, patients with high syntax high syntax score, Patients with coronary bypass grafts, previous PCI and patients with instent restenosis. PPI was defined as troponin T elevation (N 0.1 ng/mL) at 6–24 h post-PCI. Results: Patients were classified according to presence or absence of diabetes mellitus (DM) into two groups; group I (non-diabetic patients DM; 33 patients, 23 males, 10 females, their age ranged from 42- 62 years with mean 50.2±5.3 years), group II (diabetic patients; 27 patients, 16 males, 11 females, their age ranged from 45 -65 years with mean age of 54.4±5.4 years). Patients were reclassified according to syntax score into two groups; group A (with low score (0-22); 48 patients) & group B (with intermediate score (22-32); 12 patients).The mean patient SXscore was higher in diabetic patients and non diabetic patients (22.6 vs. 12.4, p = 0.0001), Gensini score was significantly higher in diabetic patients (52.4 vs. 25.3, p = 0.15). Also mean PCI vessel SXscore was higher in vessels associated with PPI (12.1 vs. 7.6, p = 0.002), but not different for PCI vessel Gensini score (16.2 vs. 13.6, p = 0.42). No vessels with AHA type A lesions were associated with PPI. Higher AHA classification (B and C) were associated with PPI. In total, 60 patients undergoing PCI to 77 vessels were included in the analysis, There were 43/60 (71.6%) patients who had myocardial injury. The incidence of PPI among diabetic patients was higher than non diabetic patients (24/27, 88.9% vs 19/33, 57.6% respectively) reflecting procedural complexity, (long lesion and total occlusion) more in diabetic patients. Indeed, the procedural complexity reflected by the mean patient SXscore was higher in the diabetic patients group than non diabetic patients undergoing day case PCI. By ROC analysis, we found that a patient with high SXscore of ≥ 15 can be considered as predictor of PPI with a sensitivity of 95.3% and specificity of 88.2%.Conclusion: Higher SXscores are predictive of myocardial injury, whilst AHA type A lesions have a high negative predictive value for PPI.

237 IN-VIVO QUANTITATIVE T2 MAPPING OF CAROTID PLAQUES IN PATIENTS WITH RECENT CEREBROVASCULAR EVENTS: AHA PLAQUE TYPE CLASSIFICATION AND CORRELATION WITH PLAQUE HISTOLOGY

<h3>Introduction</h3> Although in-vivo multicontrast MRI is capable of characterizing atherosclerotic plaques in carotid arteries, its non-quantitative nature and the need for extensive post-acquisition interpretation limit its widespread clinical application. Quantitative T2 mapping is a promising alternative since it can provide an absolute physical measure of plaque components that can be standardised among different MRI systems and widely adopted in multi-centre studies. The purpose of this pilot study is to seek the potential of in-vivo T2 mapping and its correlation with different plaque components <i>ex-vivo</i> on histology. <h3>Methods</h3> <i>3T-MRI</i>: 15 asymptomatic patients (11 males, 71±10 years) and 13 patients scheduled for endarterectomy (9 males, 70±17 years) were imaged at 3T using the conventional multicontrast protocol and Multiple-Spin-Echo (Multi-SE). T2 maps were generated by mono-exponential fitting to the series of images acquired by Multi-SE using non-linear least-squares regression. Two reviewers independently classified plaque types according to the MRI-modified AHA scheme, one using T2 maps+TOF images, the other using multicontrast MRI. <h3>Histology</h3> Carotid plaques were freshly obtained at time of endarterectomy. Plaques were divided at the level of maximal stenosis and 4mm-segments on either side of the cut were processed for formalin-fixed, paraffin-embedded (FFPE) sections and cryosections, respectively. FFPE sections were stained for H&amp;E and Masson’s trichrome, while cryosections were used for Oil-Red-O/adipophilin (foam cells marker) staining to visualize lipid. MRI-histology matching was performed for each segment using the carotid bifurcation as the common anatomical landmark. AHA plaque type was determined by an independent reviewer. <h3>Results</h3> In the 15 asymptomatic patients, AHA plaque type classified on multicontrast MRI and on T2 maps (+TOF) showed good agreement (76% of matching classifications and Cohen’s κ=0.68). 4 of the 13 patients scheduled for endarterectomy were excluded due to severe MRI motion artefacts. AHA type classification of the remaining 9 plaques using T2 maps (+TOF) vs. histology is presented in Table&nbsp;1. Figure&nbsp;1 shows a type VI and Figure&nbsp;2 a type IV-V plaque. T2 maps were able to differentiate lipid-rich necrotic core (LRNC), fibrous tissue, calcification, and recent intraplaque-haemorrhage (IPH). <h3>Conslusions</h3> These preliminary results show the potential of in-vivo T2 mapping for atherosclerotic plaque characterization. Agreement between AHA plaque types classified by T2 maps (+TOF) and by conventional multicontrast MRI was good. The ability of T2 maps to discriminate LRNC, fibrous tissue and recent IPH was confirmed by histology. Further prospective quantitative validation study is now underway.

Abstract WP134: Expression of Nox4 and Nox5 are Associated with Carotid Vulnerable Atherosclerotic Plaque in a Swine Model

Purpose: Fibrous cap rupture from atherosclerotic plaque can send distal emboli and lead to stroke in patients with carotid disease. The NADPH oxidases (Nox) family play an important role in the pathophysiology of atherosclerosis. However, the relationship of Nox expression with atherosclerotic plaque vulnerability remain elusive. We aim to assess the association of Nox4 and Nox5 expression with carotid plaque vulnerability in a swine model. Methods: Carotid atherosclerosis was induced in miniswines using partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography. Carotid artery sections were obtained for histologic examination and immunohistochemical study for Nox4 and Nox5 at 3 months. The atherosclerotic lesions of AHA type IV to VI were defined as advanced plaques. The association of Nox4 and Nox5 expression in the plaque with the feature of plaque vulnerability was analyzed. Results: Seventy-five carotid segments from ten carotid artery models had fibrous cap plaques with AHA type IV to VI. Distal embolism with the presence of atheroemboli was found in all rete mirabilis, and deemed to be from the ipsilateral carotid plaques. Positive staining of Nox4 and Nox5 were mostly distributed in the surrounding of lipid core, endothelium and plaque shoulder. Increased expression of Nox4 in the plaque was associated with the features of a large lipid core, marked foam cell and thin fibrous cap (p&lt;0.01). Overexpression of Nox5 in the plaque was associated with marked foam cell and cap rupture (p&lt;0.05). Co-overexpression of Nox4 and Nox 5 in the plaque was associated with thin cap (p&lt;0.05). Low expression of both Nox4 and Nox5 in the plaque was associated with less thin cap and less cap rupture (p&lt;0.01). There was a higher frequency of thin cap and cap rupture in 27 plaques with co-overexpression of Nox4 and Nox 5 than in 26 plaques with low expression of both Nox4 and Nox5. Conclusion: Nox4 and Nox5 are both expressed in carotid atherosclerotic plaques in a swine model, and their overexpression in carotid plaques are associated with thin fibrous cap and cap rupture. Upregulated Nox4 and Nox5 may participate in the process of vulnerable atherosclerotic plaque and may be used as a target for reducing the risk of distal embolism.

Abstract WP151: 18 F-FDG Uptake Identify Vulnerable Carotid Plaque on PET/CT in a Swine Model

Purpose: The imaging modality 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) has been recently used to identify inflammation in the atherosclerotic plaque. Increased uptake of 18 F-FDG in human atherosclerotic plaque on PET may predict plaque vulnerability, however, there is a lack of histological validation for PET imaging. The aim of this study is to evaluate the association of plaque vulnerability with FDG uptake on serial PET/CT scans in a swine model. Methods: Twenty carotid atherosclerotic models was induced in 10 miniswines using partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by carotid angiography. Serial 18 F-FDG PET/CT scans were performed at 0, 4, 8 and 12 weeks. MR scan for imaging-histologic correlation was performed at 12 weeks, and carotid artery sections were obtained for histopathological examination. The atherosclerotic lesions of AHA type IV to VI were defined as advanced plaques. Carotid arteries were evaluated for increased FDG uptake with a maximum standardized uptake value (SUV) and target-to-backgroud ratio (TBR). The association of carotid plaque vulerability with the serial FDG uptake was analyzed. Results: Various stages of atherosclerotic plaques were found in carotid segments from 20 carotid arteries. Most advanced plaque had the feature of vulnerability. FDG uptake in 100 carotid plaques were analyzed. Compared with carotid segments without atherosclerosis, significantly higher FDG uptake was observed in carotid segments with atherosclerosis at 4, 8 and 12 weeks (P&lt;0.001). Mean TBR was significantly higher in advanced plaque group than in early atherosclerosis group at 4, 8 and 12 weeks (P&lt;0.01). Maximum SUV was significantly higher in advanced plaque group than in early atherosclerosis group at 12 weeks (P&lt;0.01), whereas this did not reach statistical significance at 4 and 8 weeks. FDG uptake increased continuously in both groups of advance plaque and early atherosclerosis. Conclusion: Increased plaque metabolism revealed by PET persists with time and is associated with the complexity of carotid atherosclerotic plaque in a swine model. FDG PET/CT may be useful for identification of plaque vulnerability and monitoring the progress of atherosclerotic lesions.

Abstract TP228: Fluorescent Pegylated Nanoparticles are Localized in Macrophage-rich but Relatively Stable Human Carotid Atheromata

Background: Foam cell macrophages to produce matrix-disorganizing proteolytic enzymes may render atherosclerotic plaques prone to rupture, which causes thromboembolic stroke. Macrophages within atherosclerotic lesions were reported to take up low density lipoprotein (LDL)-sized nanoparticles by fluid-phase pinocytosis, indicating that fluid-phase pinocytosis of LDL is a mechanism for macrophage foam cell formation in vivo. Objective: To invesigate if fluorescent pegylated nanoparticles that are taken up by macrophages via pinocytosis could visualize vulnerable areas of human atheromata. Methods: Fresh carotid specimens from 36 patients undergoing carotid endarterectomy (after 3T carotid MRI) were tissue-cultured in DMEM (4 mL) with the fluorescent molecular imaging probe in 37°C CO 2 incubator. Before and 4 hours after the incubation, molecular optical imaging was performed using a Cy5.5 near-infrared fluorescent (NIRF) imaging machine with a charge-coupled device camera. The atherosclerotic plaques were classified according to the American Heart Association Report using 35 microsections (5μm thickness) from various pre-determined regions of selected carotid tissues (n=11). Immunohistochemical staining for macrophages (CD68) was performed using the avidin-biotin-peroxidase method. Results: High risk lesions (AHA Type IV ~ VIII) tended to show more frequent plaque regions with strong CD68 immunoreactivity (22 / 27) than did low risk lesion (2 / 8, p = 0.003). Unexpectedly however, low risk lesions (Type I: intial lesion with foam cells; Type II: fatty steak with multiple foam cell layers) tended to show more frequent in plaque regions with both strong CD68 immunoreactivity and high Cy5.5 NIRF signal (11 / 14) than the others (10 / 21, p = 0.07), suggesting that the nanoparticles could be taken up by relatively fresh foam cells in early atherosclerotic lesions rather than end-stage apoptonecrotic macrophages in advanced atheromata. Conclusion: Preliminary analysis of this on-going prospective study shows that fluorescent pegylated nanoparticles may localize macrophage-rich but relatively stable regions of human atheromata.

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

BackgroundAtherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed.Methodology/Principal FindingsWe characterized the genes generally involved in human advanced atherosclerotic (AHA type V–VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25).ConclusionsThis study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds.

Plaque Features Associated With Increased Cerebral Infarction After Minor Stroke and TIA: A Prospective, Case-Control, 3-T Carotid Artery MR Imaging Study

The goal of this study was to determine whether a 3-T magnetic resonance imaging (MRI) protocol combining carotid atherosclerotic plaque and brain imaging can identify features of high-risk acutely symptomatic plaque that correlate with brain injury. It has previously been demonstrated that, in asymptomatic patients, MRI can identify features of carotid plaque that are associated with stroke, such as the presence of a large lipid core. We hypothesized that the early phase (<7 days) after a cerebrovascular event, when risk of recurrence is highest, may be associated with particular plaque characteristics that associate with cerebral injury. Eighty-one patients (41 presenting acutely with transient ischemic attack [TIA] or minor stroke and 40 asymptomatic controls) underwent multicontrast carotid artery MRI on 2 separate occasions, each accompanied by diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging of the brain. Complex (American Heart Association [AHA] type VI) plaques were seen in 22 of 41 patients (54%) in the symptomatic group versus 8 of 40 (20%) in the asymptomatic group (p < 0.05). They were caused by intraplaque hemorrhage (34% vs. 18%; p = 0.08), surface rupture (24% vs. 5%; p = 0.03), or luminal thrombus (7% vs. 0%; p = 0.24). Noticeably, 17 of 30 (57%) cases of AHA type VI plaque were in vessels with <70% stenosis. At follow-up scanning (>6 weeks later), only 2 cases of symptomatic AHA type VI plaque showed evidence of full healing. The presence of fibrous cap rupture was associated with higher DWI brain injury at presentation and higher total cerebral FLAIR signal at follow-up (p < 0.05). Early carotid wall MRI in patients experiencing minor stroke or TIA showed a higher proportion of "complex" plaques compared with asymptomatic controls; a majority were in arteries of <70% stenosis. Fibrous cap rupture was associated with increases in DWI and FLAIR lesions in the brain. Combined carotid plaque and brain MRI may aid risk stratification and treatment selection in acute stroke and TIA.

Stroke while squeezing a pimple

A 63-year-old man, after squeezing a skin lesion in the left cervical region (figure, A), developed right hand weakness. Cranial MRI displayed multiple ischemic lesions in the left anterior circulation (figure, B). Plaque imaging revealed a nonstenosing complicated AHA type VI plaque in the left internal carotid artery (ICA) near the site of manipulation (figure, C–E). We hypothesize that the mechanical maneuver …

German stereotaxis-guided percutaneous coronary intervention study group: first multicenter real world experience

The Niobe Stereotaxis system consists of two 0.8 Tesla magnets and a navigation software allowing to move specially designed coronary wires. The aim of this observational multicenter study was to systematically evaluate the capability of the Stereotaxis Niobe Magnetic Navigation system to facilitate wire navigation during percutaneous coronary intervention (PCI), to determine the success rate of magnetically guided PCIs in a real-world setting, and to analyze procedure-related variables influencing the outcome data. One hundred and fifty seven patients underwent magnetically guided PCI in three German centers. Demographic variables of the patients, lesion quality determined by quantitative coronary angiography, success rate of the procedure as well as radiation time were analyzed. A subanalysis was performed for two periods (06/04-10/06 and 10/06-10/07) owing to a second generation of wires which was introduced at the beginning of the second period and procured-related learning curves of the operators. Mean age of the patients was 65 +/- 0.4 years (82% male, 18% female). 25% of the patients were diabetics. The lesions were characterized by high complexity (11% AHA type A, 25% type B1, 38% type B2, 25% type C). Mean percent lesion stenosis was 83.7 +/- 11.9%. The total fluoroscopy time was 13.2 +/- 0.3 min and the fluoroscopy time to cross lesion was 90.4 +/- 62.2 s. The overall success rate of the magnetically guided approach was 89%. All failures occurred within the first period were. In these cases, 80% of the failures could be successfully treated after switching to the conventional wires. On the other hand, between 10/06 and 10/07 three conventional PCI failures could be successfully treated using the Stereotaxis system. Magnetically guided PCI represents a promising tool for the treatment of dedicated lesions. There is a marked difference in the success rates of the method between the two different time periods which were analyzed, reflecting advances in the wire development and learning curves of the respective operators. Randomized controlled trials are required to determine the method's overall value and to identify subgroups that may particularly benefit.

Heat shock factor gene family in rice: Genomic organization and transcript expression profiling in response to high temperature, low temperature and oxidative stresses

Binding of heat shock factors (HSFs) with heat shock element sequence is critical for the transcriptional induction of heat shock genes. Rice genome sequence shows 26 OsHsf genes out of which 25 possess various important domains noted in HSFs i.e. DNA binding domain (DBD), oligomerization domain (OD), nuclear localization signal (NLS), nuclear export signal (NES) and AHA type activation domain. OsHsf entry LOC_Os06g226100 has the oligomerization domain but lacks the above other domains. Also, there are no ESTs or full-length cDNA noted for this entry in database. Expression profiling showed that 22 OsHsf genes are induced by high temperature. Induction of 10 and 14 OsHsf genes was also noted against low temperature stress and oxidative stress, respectively. All OsHsf genes induced by oxidative stress were also induced by high temperature. On the other hand, induction of 6 and 1 OsHsf genes was noted to be exclusive to high and low temperature stresses, respectively. Seven OsHsf genes showed induced expression in response to all the three stresses examined. While in silico promoter analysis showed that OsHsf genes contain upstream regulatory elements corresponding to different abiotic stresses, there was lack of correlation noted between the in silico profiling of the elements and their corresponding transcript expression patterns. Apart from stress inducibility, EST database suggests that various OsHsf genes are developmentally regulated in diverse tissue types.