Ciaran McDonnell

Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence.

Symptomatic carotid stenosis is associated with a 3‐fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque‐related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined 18F‐fluorodeoxyglucose positron‐emission tomography (FDG‐PET)/computed tomography, we investigated the relation between inflammation‐related FDG uptake and stroke recurrence.

Plaque Inflammation and Unstable Morphology Are Associated With Early Stroke Recurrence in Symptomatic Carotid Stenosis

Background and Purpose— Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque. Methods— Carotid endarterectomy tissue from consecutive patients with ipsilateral stenosis ≥50% and recent symptoms were analyzed using a validated histopathologic algorithm (Oxford Plaque Study [OPS] system). Nonprocedural stroke recurrence before carotid endarterectomy was ascertained at 7, 28, and 90 days after initial symptoms. Results— Among 44 patients meeting eligibility criteria, 27.3% (12/44) had stroke recurrence after initial stroke/transient ischemic attack but before carotid endarterectomy. Compared with patients without recurrence, stroke recurrence was associated with dense macrophage infiltration (OPS grade ≥3; 91.7% versus 37.5%; P=0.002), extensive (>25%) fibrous cap disruption (90.9% versus 37%; P=0.004), neovascularization (OPS grade ≥2; 83.3% versus 43.8%; P=0.04), and low plaque fibrous content (OPS grade <2; 50% versus 6.3%; P=0.003). Early recurrence rates were 82.3% (confidence interval, 49.2%–98.8%) in patients with extensive plaque macrophage infiltration (OPS grade ≥3) compared with 22.2% (confidence interval, 3.5%–83.4%) in those with OPS grade <3 (log-rank P=0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or <3), age, and severity of stenosis (50%–69% or ≥70%), plaque inflammation was the only variable independently predicting stroke recurrence (adjusted hazard ratio, 9; confidence interval, 1.1–70.6; P=0.04). Conclusions— Plaque inflammation and other vulnerability features were associated with highest risk of stroke recurrence and may represent therapeutic targets for future stroke prevention trials.

Use of Colour Duplex Ultrasound as a First Line Surveillance Tool Following EVAR is Associated with a Reduction in Cost Without Compromising Accuracy

INTRODUCTION CT scanning remains the postoperative surveillance imaging modality of choice following EVAR. Concerns regarding cost, exposure to ionising radiation and intravenous contrast have led to a search for a less expensive, equally efficacious and safer method of monitoring EVAR patients after endograft deployment. This study evaluated the cost saving obtained if CDUS was employed as a first line surveillance tool following EVAR, as well as comparing the two entities in terms of efficacy. PATIENTS & METHODS Postoperative surveillance CTs and CDUS scans in the 145 patients who have undergone EVAR from 1st June 2003 to 1st July 2010 were compared for the detection of endoleak and determination of residual sac size. RESULTS Adopting a protocol where CDUS was employed as the first line surveillance tool following EVAR would result in a reduction in the number of postoperative CTs required in 2010 from 235 to 36. Based on 2010 costings, this would equate to an estimated reduction in expenditure from €117,500 to €34,915 a saving of €82,585. CDUS had a sensitivity of 100% and a specificity of 85% in the detection of endoleaks compared to CT. The positive predictive value was 28% and negative predictive value 100%. The Pearson Coefficient correlation of 0.96 indicates a large degree of correlation between CDUS and CT when measuring residual aneurysm size following EVAR. CONCLUSION CDUS can replace CT as the first line surveillance tool following EVAR. This is associated with a significant reduction in the cost of surveillance without any loss of imaging accuracy.

The importance of expert feedback during endovascular simulator training

OBJECTIVES Complex endovascular skills are difficult to obtain in the clinical environment. Virtual reality (VR) simulator training is a valuable addition to current training curricula, but is there a benefit in the absence of expert trainers? METHODS Eighteen endovascular novices performed a renal artery angioplasty/stenting (RAS) on the Vascular Interventional Surgical Trainer simulator. They were randomized into three groups: Group A (n = 6, control), no performance feedback; Group B (n = 6, nonexpert feedback), feedback after every procedure from a nonexpert facilitator; and Group C (n = 6, expert feedback), feedback after every procedure from a consultant vascular surgeon. Each trainee completed RAS six times. Simulator-measured performance metrics included procedural and fluoroscopy time, contrast volume, accuracy of balloon placement, and handling errors. Clinical errors were also measured by blinded video assessment. Data were analyzed using SPSS version 15. RESULTS A clear learning curve was observed across the six trials. There were no significant differences between the three groups for the general performance metrics, but Group C made fewer errors than Groups A (P = .009) or B (P = .004). Video-based error assessment showed that Groups B and C performed better than Group A (P = .002 and P = .000, respectively). CONCLUSION VR simulator training for novices can significantly improve general performance in the absence of expert trainers. Procedure-specific qualitative metrics are improved with expert feedback, but nonexpert facilitators can also enhance the quality of training and may represent a valuable alternative to expert clinical faculty.

Serum lipids associated with inflammation-related PET-FDG uptake in symptomatic carotid plaque

Objective: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on 18fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. Methods: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). Results: Sixty-one patients were included. Plaque inflammatory FDG SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01), and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho −0.37, p = 0.004) and SUVROImax (rho −0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p = 0.008) and total cholesterol (p = 0.04) were independently associated with SUVmax. Conclusion: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.

Statins Promote Residual Aneurysm Sac Regression Following Endovascular Aortic Aneurysm Repair

Background: Regression of the residual sac is indicative of successful endovascular aortic aneurysm (EVAR) repair. Using color duplex ultrasound (CDU), we monitored the residual aneurysm sac following EVAR and correlated sac behavior with perioperative risk factors. Methods: Of 145 patients with EVAR, 106 (73.1%) patients between January 01, 2003, and July 01, 2010, had at least 2 consecutive postoperative scans and thus were eligible for inclusion. Mean (± standard deviation [SD]) CDU scans per person was 4.6 (±1.4). All were conducted by the same technologist using a standard protocol on the same machine. Aneurysm sac change in centimeters and percentage terms was calculated. The presence or absence of an endoleak was also recorded. Change in aneurysm sac size was correlated with preoperative risk factors. Findings: Mean sac size change at 1 month was a decrease of 0.24 cm, equating to a percentage change of 4.3%. At 7 months, the decrease was 0.59 cm (9.8%), at 12 months, 0.73 cm (12.4%), at 18 months 0.92 cm (15.8%), and at 36 months 1.0 cm (16.6%). Both univariate and multivariate analyses demonstrated that statin therapy (P = .002) was the only risk factor variable positively associated with aneurysm regression while the presence of an endoleak was inversely related to sac reduction (P = .01). Interpretation: Maximum aneurysmal sac reduction seems to occur in the first year following endograft implantation. Statin therapy appears to be associated with an increased likelihood of sac regression following EVAR. Further investigation of the role of statins in the biology of abdominal aortic aneurysmal disease is warranted.

Screening for Peripheral Arterial Disease and Carotid Artery Disease in Patients With Abdominal Aortic Aneurysm.

Screening for concomitant atherosclerotic disease is important in cardiovascular risk reduction. This study assessed the prevalence of carotid artery disease (CAD) and peripheral arterial disease (PAD) in patients with known abdominal aortic aneurysms (AAAs). All patients with AAA attending the vascular laboratory between the January 1, 2007, and December 31, 2009, were eligible for a carotid ultrasound and measurement of ankle brachial indices. A total of 389 (305 males) patients were identified on the AAA surveillance program with a mean (±standard deviation) age of 76 (±8) years. The mean age of the males was 75.4 (±7.8) years, and the mean age of the females was 77 (±11) years. A total of 332 patients were assessed for CAD, and 101 (30.4%) of those were found to have significant disease. A total of 289 patients were assessed for PAD of which 131 (45.3%) were found to have PAD at rest, and 289 patients were assessed for both and 59 (20.4%) patients had significant CAD + PAD. Patients with AAAs are at high risk of other atherosclerotic disorders, and, therefore, they should receive intensive medical optimization.

Eversion Endarterectomy for External Iliac Artery Occlusive Disease

Introduction: The advent of effective endovascular techniques has revolutionized the treatment of iliac occlusive disease. Long-segment iliac occlusions remain technically difficult to treat, particularly in the presence of femoral disease. Iliac endarterectomy is an established procedure for the treatment of iliac occlusive disease, but it has been suggested that in the era of effective endovascular intervention, its role is limited. Methods: A review of all patients who had eversion endarterectomy of the external iliac artery from a single institution between 2000 and 2008. Results: Twenty-one patients (18 male) underwent eversion external iliac endarterectomy, 15 for external iliac and 6 for iliofemoral disease. Mean age was 64.7 years (range: 46-78 years) and the modal American Society of Anaesthesiologists (ASA) grade was 3. The indications were critical ischemia (n = 16) and disabling claudication (n = 5). Twelve had adjunctive procedures. The mean follow-up was 25.3 months (range: 1-59 months). There were no technical failures. Seventeen patients had significant improvement in symptoms and three had moderate improvement. The cumulative primary patency at 1 year was 81%. One patient had no improvement (because of infrainguinal occlusive disease), and subsequently required femoro-popliteal bypass. There was no systemic morbidity within 30 days. There was 1 in-hospital death from sudden cardiac arrest (47 days postoperatively). Six patients died during follow-up (from unrelated illness). Conclusion: Eversion external iliac endarterectomy is an effective means of treating iliofemoral occlusive disease with excellent short-term outcomes and a low complication rate in a cohort with high levels of comorbidity.

A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents

Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature. In the present work, we demonstrate the ability of Lipogel to provide a flexible, easily modifiable release platform. It is possible to tune the release kinetics of different drugs providing a passive release of one therapeutic agent loaded within the gel and activating the release of a second LTSL encapsulated agent via a hyperthermic stimulus. In addition, it was possible to modify the drug dosage within Lipogel by varying the duration of hyperthermia. This can allow for adaption of drug dosing in real time. As an in vitro proof of concept with this system, we investigated Lipogels ability to recruit stem cells and then elevate their production of vascular endothelial growth factor (VEGF) by controlling the release of a pro-angiogenic drug, desferroxamine (DFO) with an external hyperthermic stimulus. Initial cell recruitment was accomplished by the passive release of hepatocyte growth factor (HGF) from the hydrogel, inducing a migratory response in cells, followed by the delayed release of DFO from thermosensitive liposomes, resulting in a significant increase in VEGF expression. This delayed release could be controlled up to 14days. Moreover, by changing the duration of the hyperthermic pulse, a fine control over the amount of DFO released was achieved. The ability to trigger the release of therapeutic agents at a specific timepoint and control dosing level through changes in duration of hyperthermia enables sequential multi-dose profiles. STATEMENT OF SIGNIFICANCE This paper details the development of a heat responsive liposome loaded hydrogel for the controlled release of pro-angiogenic therapeutics. Lysolipid-based thermosensitive liposomes (LTSLs) embedded in a chitosan-based thermoresponsive hydrogel matrix represents a novel approach for the spatiotemporal release of therapeutic agents. This hydrogel platform demonstrates remarkable flexibility in terms of drug scheduling and sequencing, enabling the release of multiple agents and the ability to control drug dosing in a minimally invasive fashion. The possibility to tune the release kinetics of different drugs independently represents an innovative platform to utilise for a variety of treatments. This approach allows a significant degree of flexibility in achieving a desired release profile via a minimally invasive stimulus, enabling treatments to be tuned in response to changing symptoms and complications.

Importance of strict patient selection criteria for combined carotid endarterectomy and coronary artery bypass grafting

BACKGROUND Management of patients with severe concomitant carotid and coronary disease remains controversial. We report our experience of combined carotid endarterectomy (CEA) and coronary artery bypass surgery (CABG) over a fifteen year period using strict patient selection criteria. METHODS From 1st January 1995 to December 31st 2009 165 patients underwent combined CABG/CEA procedures at the Mater Hospital. Mean age was 68.2 years (range 43-88) and 127 (77%) were male. Fifty-three (32%) had symptomatic carotid disease. Indications for combined procedures were the presence of symptomatic >70% or asymptomatic >80% internal carotid artery stenosis in a patient requiring urgent CABG because of either unstable angina, recent MI, severe triple vessel disease or severe Left Anterior Descending or Left Main Stem stenosis. RESULTS Thirty-day stroke and death rate was 3%. All neurological events were in the hemisphere contralateral to the carotid surgery and symptoms had completely resolved prior to discharge from hospital. One patient required evacuation of a cervical haematoma and there were two transient XII nerve palsies. CONCLUSION Combined CEA/CABG can be performed safely with acceptable morbidity and mortality in patients selected in accordance with strict criteria in a centre with a large experience of both cardiac and carotid surgery.