Edward Choke

Color duplex ultrasonography is insensitive for the detection of endoleak after aortic endografting: a systematic review.

Purpose: To synthesize the available evidence regarding the diagnostic accuracy of color duplex ultrasonography (CDU) versus the accepted gold-standard of contrast-enhanced computed tomography (CT) for the detection and classification of endoleaks after aortic endografting. Methods: A systematic search of the literature was conducted using electronic bibliographical databases and other means to gather articles published between 1991 and 2004. Articles were scrutinized against inclusion/exclusion criteria that broadly followed the QUA-DAS quality assessment guidelines. The results of diagnostic CDU were expressed for each study as a 2times2 contingency table, and summary statistics (sensitivity/specificity with 95% confidence intervals [CI]) were calculated. Pooled and random effects meta-analyses were performed. Results: Eight published studies and 2 unpublished studies from Charing Cross and St. Georges Hospitals (711 patients, 1355 paired scans performed ≥1 month after endografting) were eligible for inclusion. From meta-analyses, the pooled sensitivity of CDU (versus CT as the gold standard) was 69% (95% CI 52% to 87%) and the specificity of CDU was 91% (95% CI 87% to 95%). These parameters did not appear to vary over time when a smaller dataset of 117 patients with 239 paired scans was used to compare CT and CDU specifically at 3, 12, and 24 months after endografting. Endoleak classification data, which was derived from only 5 small studies, indicated that CDU appeared to have better diagnostic accuracy in detecting type I or type III endoleaks compared with type II endoleaks; however, the data were insufficient for statistical analysis. Conclusions: CDU currently does not have sufficient diagnostic accuracy for the detection of all endoleaks in routine clinical practice. The diagnostic accuracy of CDU may improve if type II endoleaks are ignored.

Outcomes of Endovascular Abdominal Aortic Aneurysm Repair in Patients with Hostile Neck Anatomy

PurposeThe principal anatomic contraindication to endovascular aneurysm repair (EVR) is an unfavorable proximal aortic neck. With increasing experience, a greater proportion of patients with unfavorable neck anatomy are being offered EVR. This study aimed to evaluate outcomes in patients with challenging proximal aortic neck anatomy.MethodsProspectively collected data from 147 consecutive patients who underwent EVR between December 1997 and April 2005 were supplemented with a retrospective review of medical records and radiological images. Unfavorable anatomic features were defined as neck diameter >28 mm, angulation >60°, circumferential thrombus >50%, and length <10 mm. Eighty-seven patients with 0 adverse features (good necks) were compared with 60 patients with one or more adverse features (hostile necks).ResultsComparing the good neck with the hostile neck group, there were no significant differences in the incidence of primary technical success (p = 0.15), intraoperative adjunctive procedures (p = 0.22), early proximal type I endoleak (<30 days) (p = 1.0), late proximal type I endoleak (>30 days) (p = 0.57), distal type I endoleak (p = 0.40), type III endoleak (p = 0.51), secondary interventions (p = 1.0), aneurysm sac expansion (p = 0.44), or 30 day mortality (p = 0.70). The good neck group had a significantly increased incidence of type II endoleak (p = 0.023). By multivariate analysis, the incidence of intraoperative adjunctive procedures was significantly increased in the presence of severe angulation (p = 0.041, OR 3.08, 95% CI 1.05–9.04).ConclusionPatients with severely hostile proximal aortic neck anatomy may be treated with EVR, although severely angulated necks require additional intraoperative procedures. Early outcomes are encouraging and suggest that indications for EVR may be expanded to include patients with hostile neck anatomy.

Whole genome-expression profiling reveals a role for immune and inflammatory response in abdominal aortic aneurysm rupture.

OBJECTIVES This study used the whole transcriptome approach to investigate the role of genes involved in immune and inflammatory response at the site of aneurysm rupture. MATERIALS AND METHODS Rupture site and paired anterior sac biopsies (internal control) of ruptured abdominal aortic aneurysms (AAAs) (n=10) were analysed with Affymetrix Human Genome U133A plus 2.0 microarray. Twenty-one differentially expressed genes were selected for validation using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). RESULTS A total of 139 genes (123 upregulated, 16 downregulated) at the aneurysm rupture site were differentially expressed (>2.5-fold, P<0.005). Immune and inflammatory responses (Gene Ontology Classification) were frequently associated with the differentially expressed genes. Genes with immune and inflammatory functions that were confirmed, by QRT-PCR, to be overexpressed at the aneurysm rupture site were interleukins-6 and -8 (IL-6 and -8), Selectin E (SELE), prostaglandin-endoperoxidase synthase 2 (COX2) and prokineticin 2 (PROK2). IL-6 (pro-immune) and IL-8 (pro-immune and pro-inflammatory) have previously been linked to aneurysm rupture; and SELE and COX2 (pro-inflammatory) have previous associations with aneurysm development but not rupture. CONCLUSIONS The differential expression of genes involved in immune and inflammatory responses was confirmed at AAA rupture site. These genes may represent novel targets for treatment of aneurysms.

Elevated Plasma MMP1 and MMP9 are Associated with Abdominal Aortic Aneurysm Rupture

BACKGROUND The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) formation is well established. However the changes in plasma MMP levels with AAA rupture have not been reported. The aim of this study was to determine circulating levels of MMPs in non-ruptured and ruptured AAA immediately prior to open repair. METHODS Concentrations of MMPs and their endogenous tissue inhibitors (TIMPs) were quantified using ELISA in pre-operative plasma samples from non-ruptured and ruptured AAA. RESULTS MMP1 and MMP9 were elevated in the plasma of ruptured AAA versus non-ruptured AAA. A four-fold elevation in pre-operative plasma MMP9 was associated with non-survival at 30 days from rupture surgery compared with those surviving for greater than 30 days. CONCLUSION In conclusion, these findings support the role of MMPs in AAA pathogenesis. Elevation of MMP9 was associated with ruptured aneurysm related 30-day mortality and may represent a survival indicator in this group.

A Randomised Placebo-controlled Double-blind Trial to Evaluate Lipid-lowering Pharmacotherapy on Proteolysis and Inflammation in Abdominal Aortic Aneurysms

OBJECTIVES Modulation of abdominal aortic aneurysm (AAA) expansion by HMG-CoA reductase inhibitors (statins) might be linked to reducing IL-6 and MMP-9, which may be consequent on reducing plasma cholesterol. Ezetimibe is a novel cholesterol absorption inhibitor used in combination with statins. This pilot study compared the biological effects of ezetimibe combination therapy with simvastatin alone on parameters relevant to aneurysm expansion including cytokines and proteolytic enzymes. DESIGN Randomised placebo-controlled double-blind trial. MATERIALS & METHODS Eighteen patients scheduled for elective open AAA repair were randomised to simvastatin 40 mg plus ezetimibe 10 mg (n = 9), or simvastatin 40 mg plus placebo (n = 9), for 32.5 days (IQR 28-50.5) until the day of surgery. Total concentrations of TNF-α, IL-1β, IL-6, IL-8, IL-10, MMPs-1, -2, -3, -8, -9, -12, -13, TIMP-1 and -2 were measured in plasma, aortic wall homogenates and tissue culture explants. RESULTS Two patients in the placebo arm did not undergo open repair precluding aortic samples. Ezetimibe was associated with a significant reduction in aortic wall MMP-9 (p = 0.02) and aortic wall IL-6 (p = 0.02), associated with a reduction in plasma lipids. CONCLUSIONS These results suggest that ezetimibe combination therapy reduces aortic wall proteolysis and inflammation, key processes that drive AAA expansion. A larger RCT is justified focussing on aneurysm growth rates in small AAA.

Vascular endothelial growth factor enhances angiotensin II-induced aneurysm formation in apolipoprotein E-deficient mice

OBJECTIVE Abdominal aortic aneurysm (AAA) development is associated with increased angiogenesis and overexpression of vascular endothelial growth factor (VEGF). Inhibition of angiogenesis results in attenuation of experimental aneurysms. This study investigated the effects of recombinant human (rh)VEGF on experimental aneurysms. METHODS Apolipoprotein E-deficient (apoE(-/-)) mice were assigned to one of four groups: (1) normal saline infusion (sham), (2) angiotensin-II (AngII) infusion, (3) AngII infusion plus 100 microg daily rhVEGF for 14 days (AngII+14dVEGF), or (4) AngII infusion plus 100 microg daily rhVEGF for 21 days (AngII+21dVEGF). Aortic maximum diameter and cross-sectional area were determined by magnetic resonance imaging and microscopy. All mice were sacrificed at day 28. RESULTS Aneurysms developed in all mice in the AngII+14dVEGF and AngII+21dVEGF groups by day 21 compared with 40% in the AngII group. Treatment with rhVEGF increased maximum aortic diameter (P < .002) and cross-sectional area of aneurysms (P < .005) at day 21. This effect was maintained at day 28 (P < .0005). Decreasing rhVEGF treatment from 21 to 14 days did not attenuate aneurysm formation. Treatment with rhVEGF upregulated matrix metalloproteinase 2 gene expression within the aortic wall (P < .0009). CONCLUSIONS Treatment with rhVEGF intensified the formation of AngII-induced aneurysms. Further studies are needed to investigate if antiangiogenic therapy may be a valid medical therapy against aneurysm expansion or rupture.

Pharmacotherapy of Abdominal Aortic Aneurysms

Aortic aneurysms account for 10,000 deaths annually in the UK, due to rupture. At present the only effective therapeutic strategy to treat abdominal aortic aneurysms is to surgically repair them; this carries an elective mortality of up to 10%. Recent advances in vascular biology have led to a greater understanding of the pathophysiological process that causes aortic aneurysms to expand and rupture. Key pathological processes include widespread aortic inflammation, proteolytic degradation of the extracellular matrix, neovascularisation and generation of reactive oxygen species. Identification of these processes has lead to pharmacological strategies to prevent aneurysm expansion and rupture. Many of these strategies have undergone proof of concept in animal models and some have now entered clinical trials. This review outlines current thinking regarding the molecular events leading to aneurysm expansion and explains how these processes may be inhibited. Experimental data on agents retarding aneurysm expansion in animal models are discussed. A significant proportion of the review details pharmacological agents that have undergone or are undergoing clinical trials. Pharmacological treatment for abdominal aneurysms is urgently required given the number of small aneurysms being diagnosed by screening programmes. This is a rapidly evolving field and one in which translation from experimental research to clinical practice is anticipated within 5 years.

Visceral and renal artery complications of suprarenal fixation during endovascular aneurysm repair.

BackgroundThe effect of suprarenal fixation of endovascular grafts on renal and visceral artery function remains undefined. This study aimed to determine renal and visceral artery complications following suprarenal fixation during endovascular aneurysm repair (EVR).MethodsProspectively collected data from 112 patients who received suprarenal fixation (group SF) and 36 patients who received infrarenal fixation (group IF) in a single institution from December 1997 to April 2005 were reviewed retrospectively. Median follow-up was 26 months (range 0.1–101 months).ResultsStent struts extended to or above the level of 106 (94.6%) right renal arteries, 104 (92.9%) left renal arteries, 49 (43.8%) superior mesenteric arteries (SMA), and 7 (6.3%) celiac arteries in group SF. This group had 2 (1.8%) unintentional main renal artery occlusions, of which 1 was successfully treated at the first procedure with a renal stent. There was 1 (0.9%) SMA occlusion which resulted in bowel infarction and death. Group IF had no renal or visceral artery complications. There were no late-onset occlusions or infarcts. There was no significant difference in median serum creatinine between groups SF and IF at 1 month (p = 0.18) and 6 months to 12 months (p = 0.22) follow-up. The change in serum creatinine over time was also not significantly different within each group (SF, p = 0.09; IF, p = 0.38).ConclusionsIn this study, suprarenal fixation was associated with a very small incidence of immediate renal and visceral artery occlusion. There did not appear to be any medium-term sequelae of suprarenal fixation.

The Long-term Effects of Open and Endovascular Aneurysm Repair on Circulating Interleukin-6

Interleukin-6 (IL-6) is associated with abdominal aortic aneurysm (AAA) development and is an independent risk factor for cardiovascular mortality. We tested the hypothesis that aneurysm repair reduces circulating IL-6 by comparing concentrations in patients with large AAA awaiting repair (n=50) with patients having undergone open (n=34) or endovascular (n=66) repair. Only open repair was associated with a significant reduction in IL-6 (p=0.025). These results suggest that AAAs remain biologically active following endovascular repair. Aneurysm-derived IL-6 may have serious implications for cardiovascular health, and attention should be directed to modifying cardiovascular risk factors in these patients, even after successful aneurysm repair.

Contemporary management of the infra-renal abdominal aortic aneurysm.

Abdominal aortic aneurysms (AAAs) principally affect men over 60 years of age. Aneurysms are usually asymptomatic and detected coincidentally or following the onset of symptoms. Elective repair of an AAA is considered when the diameter reaches 5.5cm or annual expansion exceeds 1 cm. Rupture represents a catastrophic event and carries an unacceptably high mortality. The advent of endovascular repair heralds an improvement in operative outcome for this disease process. In this review we provide an overview of the recent trials investigating the management of non-ruptured and ruptured aneurysms and the strategies that may be invoked to lower the mortality of this disease process