Closing the loop: a 21-year audit of strategies for preventing stroke and death following carotid endarterectomy.

The objective of this review was to identify causes of stroke/death after carotid endarterectomy (CEA) and to develop transferable strategies for preventing stroke/death after CEA, via an overview of a 21-year series of themed research and audit projects. Three preventive strategies were identified: (i) intra-operative transcranial Doppler (TCD) ultrasound and completion angioscopy which virtually abolished intra-operative stroke, primarily through the removal of residual luminal thrombus prior to restoration of flow; (ii) dual antiplatelet therapy with a single 75-mg dose of clopidogrel the night before surgery in addition to regular 75 mg aspirin which virtually abolished post-operative thromboembolic stroke and may also have contributed towards a decline in stroke/death following major cardiac events; and (iii) the provision of written guidance for managing post-CEA hypertension which was associated with virtual abolition of intracranial haemorrhage and stroke as a result of hyperperfusion syndrome. The pathophysiology of peri-operative stroke is multifactorial and no single monitoring or therapeutic strategy will reduce its prevalence. Two of the preventive strategies developed during this 21-year project (peri-operative dual antiplatelet therapy, published guidance for managing post-CEA hypertension) are easily transferable to practices elsewhere.

Reprinted article "Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature".

OBJECTIVES: To determine the role of carotid artery disease in the pathophysiology of stroke after coronary artery bypass (CABG). DESIGN: Systematic review of the literature. RESULTS: The risk of stroke after CABG was 2% and remained unchanged between 1970-2000. Two-thirds occurred after day 1 and 23% died. 91% of screened CABG patients had no significant carotid disease and had a <2% risk of peri-operative stroke. Stroke risk increased to 3% in predominantly asymptomatic patients with a unilateral 50-99% stenosis, 5% in those with bilateral 50-99% stenoses and 7-11% in patients with carotid occlusion. Significant predictive factors for post-CABG stroke included; (i) carotid bruit (OR 3.6, 95% CI 2.8-4.6), (ii) prior stroke/TIA (OR 3.6, 95% CI 2.7-4.9) and (iii) severe carotid stenosis/occlusion (OR 4.3, 95% CI 3.2-5.7). However, the systematic review indicated that 50% of stroke sufferers did not have significant carotid disease and 60% of territorial infarctions on CT scan/autopsy could not be attributed to carotid disease alone. CONCLUSIONS: Carotid disease is an important aetiological factor in the pathophysiology of post-CABG stroke. However, even assuming that prophylactic carotid endarterectomy carried no additional risk, it could only ever prevent about 40-50% of procedural strokes.

Reprinted article "Subintimal angioplasty of femoropopliteal artery occlusions: the long-term results".

The technique of subintimal angioplasty has been attempted on 200 consecutive femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The principle of the technique is to traverse the occlusion in the subintimal plane and recanalise by inflating the angioplasty balloon within the subintimal space. The technical success rate was 159/200 (80%) and was not significantly different for occlusions <10 cm (81%, n = 73), 11-20 cm (83%, n = 63) or >20 cm (68%, n = 23), p = 0.20. There were no deaths nor limb loss resulting from the procedure. The median (range) ankle-brachial pressure index increased from 0.61 (0.21-1.0) preangioplasty to 0.90 (0.26-1.50) postangioplasty. The actuarial haemodynamic patencies of technically successful procedures at 12 and 36 months were 71% and 58% respectively, the symptomatic patencies were 73% and 61%. A multiple regression analysis showed that smoking multiplied the risk of reocclusion by 2.70 (p < 0.001), each additional run-off vessel reduced the risk by 0.54 (p < 0.001) and the risk increased by 1.73 (p = 0.020) for every 10 cm of occlusion length. In conclusion, the technical success rate (80%) of subintimal angioplasty for femoropopliteal occlusions is unrelated to occlusion length and for all procedures, including technical failures, cumulative symptomatic and haemodynamic patencies of 46 and 48% can be achieved at 3 years. The factors influencing long-term patency were smoking, the number of calf run-off vessels and occlusion length.

ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques.

The European Society for Vascular Surgery brought together a group of experts in the field of carotid artery disease to produce updated guidelines for the invasive treatment of carotid disease. The recommendations were rated according to the level of evidence. Carotid endarterectomy (CEA) is recommended in symptomatic patients with >50% stenosis if the perioperative stroke/death rate is <6% [A], preferably within 2 weeks of the patient's last symptoms [A]. CEA is also recommended in asymptomatic men <75 years old with 70-99% stenosis if the perioperative stroke/death risk is <3% [A]. The benefit from CEA in asymptomatic women is significantly less than in men [A]. CEA should therefore be considered only in younger, fit women [A]. Carotid patch angioplasty is preferable to primary closure [A]. Aspirin at a dose of 75-325 mg daily and statins should be given before, during and following CEA. [A] Carotid artery stenting (CAS) should be performed only in high-risk for CEA patients, in high-volume centres with documented low peri-operative stroke and death rates or inside a randomized controlled trial [C]. CAS should be performed under dual antiplatelet treatment with aspirin and clopidogrel [A]. Carotid protection devices are probably of benefit [C].

Intravascular stapler for "open" aortic surgery: preliminary results.

OBJECTIVES: The aim of this study was to assess the efficacy of a new stapling device using a pig model. METHODS: Straight 12 mm Gore-Tex grafts were inserted end to end into the aorta of 12 pigs. One anastomosis was performed with the stapler and the other using 4/0 prolene sutures and 13 mm needles. The animals were sacrificed at one week, one and three months and all grafts underwent histological examination. Leakage from the anastomoses was assessed in a separate specially designed circulation model using saline as a perfusate. RESULTS: The stapled anastomoses took 1.0+/-0.25 minutes to complete while suturing took 8.5+/-1.5 minutes. There was no difference in the histology between the two types of anastomosis. The leak rate was six times greater at the sutured compared to the stapled anastomosis. CONCLUSION: The use of stapled anastomoses may allow a significant shortening of aortic cross clamping time, reduce anastomotic leakage and may be particularly useful in laparoscopic aortic repair. A randomised trial is required to assess the efficacy of this device.

Cerebral protection during open retrograde angioplasty/stenting of common carotid and innominate artery stenoses.

BACKGROUND: This was a retrospective study of the effectiveness of open, retrograde angioplasty/stenting of supra-aortic arterial stenoses combined with transcranial Doppler-directed dextran therapy in preventing perioperative embolization. METHODS: Eight patients underwent angioplasty/stenting of the proximal common carotid (synchronous carotid endarterectomy (CEA) in six), while four underwent angioplasty/stenting of the innominate artery (synchronous CEA in one). Open exposure of the carotid bifurcation enabled temporary carotid clamping to protect the brain from procedural embolization. Dextran was administered to patients with a high rate of embolization on transcranial Doppler after the operation. RESULTS: No emboli were recorded in the cerebral circulation during the actual angioplasty procedure when the internal carotid artery was clamped. After operation three patients developed high-rate embolization and received dextran. No strokes or deaths occurred within 30 days of treatment. One patient developed symptoms and a recurrent stenosis greater than 50 per cent during follow-up and was treated by redo angioplasty. CONCLUSION: Retrograde angioplasty/stenting with or without synchronous CEA offers an alternative approach to treating patients with supra-aortic inflow disease.

Duplex imaging immediately prior to carotid endarterectomy.

INTRODUCTION: In this centre, angiography is used only in selected cases, whilst duplex ultrasound (DU) is the main imaging method prior to carotid endarterectomy (CEA). DU has no associated morbidity and so can be repeated immediately before surgery to detect changes in the carotid plaque or degree of stenosis. PATIENTS AND METHODS: We retrospectively examined our Vascular Surgery Audit database for the last 500 patients admitted for CEA. In each case, the DU scan was repeated immediately before surgery. RESULTS: From 500 admissions, repeat DU immediately prior to surgery detected 8 (1.6%) situations where CEA would no longer have been an appropriate intervention. In four cases, the degree of stenosis was found to be less than 70% on the repeat scan - in three cases the internal carotid artery (ICA) had occluded or sub-occluded and in one case there was a dissection of the ICA plaque. CONCLUSIONS: DU can be repeated, with no associated morbidity, immediately prior to surgery. Such a practice changes management decisions in 1.6% of admissions for CEA, allowing surgery unjustified by current evidence to be avoided. This policy also serves several other important purposes: it is a method of internal validation, provides a means of improving training of vascular technologists and of achieving quality assurance in DU techniques.

HMG-CoA reductase inhibitors (statins) decrease MMP-3 and MMP-9 concentrations in abdominal aortic aneurysms.

BACKGROUND: An imbalance in matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in AAA formation. 3-Hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) are known to reduce MMP levels. The aim of this study was to investigate the in vivo effect of statins on MMP levels in AAA. METHODS: Infra-renal aortic biopsies were obtained from the anterior sac of 63 patients undergoing asymptomatic repair. Seventeen patients were taking a statin pre-operatively, while 46 were not. The concentrations of MMP-1, -2, -3, -8, -9, -13, TIMP-1 and TIMP-2 were quantified using ELISA. RESULTS: There was no difference in the concentration of MMP-1, -2, -8, -13, TIMP-1 or -2 in patients taking versus not taking a statin pre-operatively. In contrast levels of MMP-9 and MMP-3 were significantly lower in patients taking a statin. CONCLUSIONS: These data demonstrate that statins decrease MMP-9 and MMP-3 levels and represent a potential pharmacotherapy in established AAA.

Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm.

BACKGROUND: Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA. METHODS: Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression. RESULTS: MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4.5 versus 0.5 ng per mg protein, P < 0.001; total MMP-8: 16.6 versus 2.8 ng per mg protein, P < 0.001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142.2 versus 302.8 ng per mg protein; P = 0.010; TIMP-2: 9.2 versus 33.1 ng per mg protein, P < 0.001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall. CONCLUSION: The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion.

A comparison of methods for determining genotypes at the tumour necrosis factor-alpha-308, interleukin (IL)-1beta+3953, IL-6 -174 and IL-10 -1082/-819/-592 polymorphic loci.

Induced heteroduplex genotyping (IHG) is one of many methods that can be used to determine single nucleotide polymorphisms (SNPs). It is relatively new in comparison to other polymerase chain reaction (PCR)-based techniques. The aim of this study was to compare the results of genotyping using IHG with the results of genotyping using either polymerase chain reaction-sequence-specific primers (PCR-SSP) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for SNPs in the tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10 genes. Ninety patients who consented to participate in the study had their genotypes determined by IHG and either PCR-SSP (TNF-alpha-308 and IL-10 -1082/-819/-592) or PCR-RFLP (IL-1beta +3953 and IL-6 -174). Results for each locus were compared between techniques by calculating the Kappa statistic as a measure of agreement. The IHG and more traditional genotyping methods produced very similar results at all loci. The Kappa statistics for each locus were as follows: TNF-alpha -308, K = 0.727; IL-1beta +3953, K = 0.886; IL-6 -174, K = 0.909; IL-10 -1082, K = 0.876; IL-10 -592, K = 0.920. IHG is a valid method for the determination of genotypes at the loci examined in this study and produces comparable results to those of more traditional methods of genotyping.

Impact of the volume of aneurysmal contents on intraaneurysmal pressure after endovascular grafting (experimental studies).

With the purpose of clarifying the nature and outlining certain constituents of such an undesirable condition designated as "endotension", that emerges after transluminal grafting of the aneurysmally changed aorta, a basic theoretical model was worked out for explanation of "endotension". Also, there was designed and constructed in vitro an original experimental model using which the authors carried out a study into the relationship between the pressure in the aneurysm after its complete exclusion from the blood flow by an endovascular graft and the volume of the aneurysmal contents. Some factors described in the literature as influencing the pressure level in the aneurysm were at the given stage purposefully excluded. The volume of the "aneurysm" reproduced in our model was equal to 675 ml; each of five vascular grafts implanted into the aneurysm measured 110 mm in length. The pulsating liquid flow was reproduced in the system using a serial appliance for extracorporeal circulation. The liquid was aspirated from the aneurysm by means of a syringe with concurrent pressure guidance in the sac. To start pressure lowering, it was necessary to evacuate 0.4-1.6 ml of the liquid. The real clinical situations were considered from the standpoint of our results.

Patch corrugation on duplex ultrasonography may be an early warning of prosthetic patch infection.

Four of 10 patients presenting with prosthetic patch infection after carotid endarterectomy (CEA) were noted to have Duplex evidence of 'corrugation' of the prosthetic patch, without false aneurysm formation. In three, corrugation preceded diagnosis of overt patch infection by up to 11 months. In the fourth patient, awareness of the potential significance of patch corrugation enabled timely treatment of an otherwise unrecognized patch infection. Even if other imaging modalities are normal, the presence of patch corrugation on Duplex should prompt the surgeon to (at least) consider the possibility of patch infection.

An in vitro model to compare the antimicrobial activity of silver-coated versus rifampicin-soaked vascular grafts.

In situ replacement of infected vascular grafts is an accepted alternative to total graft excision and extraanatomic replacement. Its success relies upon the ability of the newly inserted graft to resist recurrent infection. This study compares the efficacy of two methods used to reduce the risk of graft reinfection: rifampicin soaking versus silver bonding of grafts. The grafts' resistance to infection was tested in vitro in two protocols, each using a panel of seven common bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The length of time the grafts remained free of organisms was compared between the groups. Both the silver graft and the rifampicin-soaked graft were significantly better than control graft at preventing bacterial growth on the graft surface. The rifampicin inhibited the growth of the gram-positive organisms, including MRSA, significantly better than the silver graft on days 2 and 3 (p < 0.001). Conversely, the silver graft was significantly more effective against the gram-negative organisms until day 4 (p < 0.0001). Both types of graft inhibit the in vitro growth of bacteria more effectively than controls, with rifampicin being most effective against gram-positive organisms and silver being best against the gram-negative organisms.

Cytokines, their genetic polymorphisms, and outcome after abdominal aortic aneurysm repair.

BACKGROUND: Excessive cytokine production has been implicated in the development of organ failure. Polymorphic sites in cytokine genes have been shown to affect levels of production in vitro and may influence cytokine production in vivo. The aims of this study were to determine if cytokines or their genetic polymorphisms were related to outcome after abdominal aortic aneurysm (AAA) repair. METHODS: A prospective study of 135 patients undergoing open AAA repair. Plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-10 were measured 24 h post-operatively and genotypes for the TNF-alpha -308, IL-1beta+3953, IL-6 -174, IL-10 -1082 and IL-10 -592 polymorphisms were determined for each patient. RESULTS: After elective AAA high levels of IL-10 were associated with both prolonged critical care (P<0.001) and hospital stay (P=0.001). The presence of a G allele at the IL-6 -174 locus was associated with a higher incidence of organ failure (P=0.04) and an A allele at TNF-alpha -308 with prolonged critical care stay (P=0.03). After ruptured AAA the development of multi-organ failure was associated with high levels of IL-6 (P=0.01) and TNF-alpha (P=0.04). High TNF-alpha levels were also associated with mortality (P=0.01). CONCLUSION: Post-operative cytokine levels are related to outcome after AAA repair. Cytokine gene polymorphisms may provide a method for determining which patients are at high risk of complications.

Unstable carotid plaques exhibit raised matrix metalloproteinase-8 activity.

BACKGROUND: The fibrous cap of atherosclerotic plaques is composed predominantly of type I and III collagen. Unstable carotid plaques are characterized by rupture of their cap, leading to thromboembolism and stroke. The proteolytic mechanisms causing plaque disruption are undefined, but the collagenolytic matrix metalloproteinase (MMP) -1, -8, and -13 may be implicated. The aim of this study was to quantify the concentrations of these collagenases in carotid plaques and to determine their relationship to markers of plaque instability. METHODS AND RESULTS: Atherosclerotic plaques were collected from 159 patients undergoing carotid endarterectomy. The presence and timing of carotid territory symptoms were ascertained. Preoperative embolization was recorded by transcranial Doppler. Each plaque was assessed for histological features of instability. Plaque MMP concentrations were quantified with ELISA. Significantly higher concentrations of active MMP-8 were observed in the plaques of symptomatic patients (20.5 versus 11.4 ng/g; P=0.0002), in plaques of emboli-positive patients (22.7 versus 13.5 ng/g; P=0.0037), and in those plaques showing histological evidence of rupture (20.8 versus 14.7 ng/g; P=0.0036). No differences were seen in the levels of MMP-1 and MMP-13. Immunohistochemistry, in situ hybridization, and colocalization studies confirmed the presence of MMP-8 protein and mRNA within the plaque, which colocalized with macrophages. CONCLUSIONS: These data suggest that the active form of MMP-8 may be partly responsible for degradation of the collagen cap of atherosclerotic plaques. This enzyme represents an attractive target for drug therapy aimed at stabilizing vulnerable plaques.

Subintimal angioplasty in lower limb ischaemia.

Subintimal angioplasty has been suggested as a treatment option for occlusive disease and has become an established practice in some centres, reducing their operative workload considerably. Others have concerns about the safety and durability of the procedure. This review will focus on the evidence for the use of subintimal angioplasty in lower limb occlusive disease. A systematic review of the literature from a Medline search has been carried out. Despite a paucity of trial data, subintimal angioplasty is now an established technique for the treatment of lower limb occlusive disease. The results for femoro-popliteal disease are well documented, with excellent technical and clinical success rates and low complication rates. The results for iliac disease are less well documented and demand caution. For infra-popliteal disease with critical ischaemia, the technique is again safe with good short and long-term results in a group of patients in whom distal bypass surgery is often risky. Subintimal angioplasty has a definite learning curve and those wishing to take it up should visit an experienced centre first. To achieve widespread acceptance it is likely to require large scale randomised controlled trials.