Carotid Stenting Prior to Coronary Bypass Surgery: An Updated Systematic Review and Meta-Analysis.

OBJECTIVES: The aim was to determine 30-day outcomes in patients with concurrent carotid and cardiac disease who underwent carotid artery stenting (CAS) followed by coronary artery bypass grafting (CABG). METHODS: This was a systematic review with searches of PubMed/Medline, Embase, and Cochrane databases. "Same-day" procedures involved CAS + CABG being performed on the same day, and "staged" interventions involved at least 1 day's delay between undergoing CAS and then CABG. RESULTS: There were 31 eligible studies (2727 patients), with 80% being neurologically asymptomatic with unilateral stenoses. Overall, the 30-day death/stroke rate was 7.9% (95% confidence interval [CI] 6.9-9.2), while death/stroke/MI was 8.8% (95% CI 7.3-10.5). Staged CAS + CABG was associated with 30-day death/stroke rate of 8.5% (95% CI 7.3-9.7) compared with 5.9% (95% CI 4.0-8.5) after "same-day" procedures. Outcomes following CAS + CABG in neurologically symptomatic patients were poorer, with procedural stroke rates of 15%. There were five antiplatelet (APRx) strategies: (a) no APRx (death/stroke/MI, 4.2%; no data on bleeding complications); (b) single APRx before CAS and CABG, then dual APRx after CABG (death/stroke/MI, 6.7%; 7.3% bleeding complications); (c) dual APRx pre-CAS down to one APRx pre-CABG (death/stroke/MI, 10.1%; 2.8% bleeding complications); (d) dual APRx pre-CAS, both stopped pre-CABG (death/stroke/MI, 14.4%); (e) dual APRx pre-CAS and continued through CABG (death/stroke/MI, 16%). There were insufficient data on bleeding complication in the last two strategies. CONCLUSIONS: In a cohort of predominantly asymptomatic patients with unilateral carotid stenoses, the 30-day rate of death/stroke was about 8%. Notwithstanding the effect of potential biases, this meta-analysis did not find evidence that outcomes after same-day CAS + CABG were higher than after staged interventions. However, outcomes were poorer in neurologically symptomatic patients. More data are required to establish the optimal antiplatelet strategy in patients undergoing same-day or staged CAS + CABG.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Restenosis after Carotid Interventions and Its Relationship with Recurrent Ipsilateral Stroke: A Systematic Review and Meta-analysis.

OBJECTIVE: Do asymptomatic restenoses > 70% after carotid endarterectomy (CEA) and carotid stenting (CAS) increase the risk of late ipsilateral stroke? METHODS: Systematic review identified 11 randomised controlled trials (RCTs) reporting rates of restenosis > 70% (and/or occlusion) in patients who had undergone CEA/CAS for the treatment of primary atherosclerotic disease, and nine RCTs reported late ipsilateral stroke rates. Proportional meta-analyses and odds ratios (OR) at end of follow-up were performed. RESULTS: The weighted incidence of restenosis > 70% was 5.8% after "any" CEA, median 47 months (11 RCTs; 4249 patients); 4.1% after patched CEA, median 32 months (5 RCTs; 1078 patients), and 10% after CAS, median 62 months (5 RCTs; 2716 patients). In four RCTs (1964 patients), one of 125 (0.8%) with restenosis > 70% (or occlusion) after CAS suffered late ipsilateral stroke over a median 50 months, compared with 37 of 1839 (2.0%) in CAS patients with no significant restenosis (OR 0.87; 95% CI 0.24-3.21; p = .8339). In seven RCTs (2810 patients), 13 out of 141 (9.2%) with restenosis > 70% (or occlusion) after CEA suffered late ipsilateral stroke over a median 37 months, compared with 33 out of 2669 (1.2%) in patients with no significant restenoses (OR 9.02; 95% CI 4.70-17.28; p < .0001). Following data correction to exclude patients whose surveillance scan showed no evidence of restenosis > 70% before stroke onset, the prevalence of stroke ipsilateral to an untreated asymptomatic > 70% restenosis was seven out of 135 (5.2%) versus 40 out of 2704 (1.5%) in CEA patients with no significant restenosis (OR 4.77; 95% CI 2.29-9.92). CONCLUSIONS: CAS patients with untreated asymptomatic > 70% restenosis had an extremely low rate of late ipsilateral stroke (0.8% over 50 months). CEA patients with untreated, asymptomatic > 70% restenosis had a significantly higher risk of late ipsilateral stroke (compared with patients with no restenosis), but this was only 5% at 37 months. Overall, 97% of all late ipsilateral strokes after CAS and 85% after CEA occurred in patients without evidence of significant restenosis or occlusion.

Stroke/Death Rates Following Carotid Artery Stenting and Carotid Endarterectomy in Contemporary Administrative Dataset Registries: A Systematic Review.

BACKGROUND: Randomised trials have reported higher stroke/death rates after carotid artery stenting (CAS) versus carotid endarterectomy (CEA). Despite this, the 2011 American Heart Association (AHA) guidelines expanded CAS indications, partly because of the Carotid Revascularization Endarterectomy versus Stenting Trial, but also because of improving outcomes in industry sponsored CAS Registries. The aim of this systematic review was: (i) to compare stroke/death rates after CAS/CEA in contemporary dataset registries, (ii) to examine whether published stroke/death rates after CAS fall within AHA thresholds, and, (iii) to see if there had been a decline (over time) in procedural risk after CAS/CEA. METHODS: PubMed/Medline, Embase, and Cochrane databases were systematically searched according to the recommendations of the PRISMA statement from January 1, 2008 until February 23, 2015 for administrative dataset registries reporting outcomes after both CEA and CAS. RESULTS: Twenty-one registries reported outcomes involving more than 1,500,000 procedures. Stroke/death after CAS was significantly higher than after CEA in 11/21 registries (52%) involving "average risk for CEA" asymptomatic patients and in 11/18 registries (61%) involving "average risk for CEA" symptomatic patients. In another five registries, CAS was associated with higher stroke/death rates than CEA for both symptomatic and asymptomatic patients, but formal statistical comparison was not reported. CAS was associated with stroke/death rates that exceeded risk thresholds recommended by the AHA in 9/21 registries (43%) involving "average risk for CEA" asymptomatic patients and in 13/18 registries (72%) involving "average risk for CEA" symptomatic patients. In 5/18 registries (28%), the procedural risk after CAS in "average risk" symptomatic patients exceeded 10%. CONCLUSIONS: Data from contemporary administrative dataset registries suggest that stroke/death rates following CAS remain significantly higher than after CEA and often exceed accepted AHA thresholds. There was no evidence of a sustained decline in procedural risk after CAS.

Fate of Distal False Aneurysms Complicating Internal Carotid Artery Dissection: A Systematic Review.

BACKGROUND: False aneurysm formation occurs in 13-49% of internal carotid artery dissections (ICADs). In light of the uncertainty regarding the clinical course, expansion rates and optimal treatment of post-ICAD false aneurysms, a systematic review of the literature was undertaken to establish the fate of the nonoperated distal ICA false aneurysm after ICAD. METHODS: PubMed/MEDLINE, Embase, and Cochrane databases were systematically searched up to 13 August 2015 for studies reporting clinical outcomes and imaging surveillance in patients who were found to have developed a false aneurysm associated with ICAD, with specific emphasis on the fate of the nonoperated false aneurysm. RESULTS: Eight studies reported on the course/clinical outcome of ICAD-associated false aneurysms in 166 patients. Of these, five of 166 false aneurysms (3%) increased in size; 86 of 166 (52%) remained unchanged in diameter; 35 of 166 (21%) diminished in size; 32 of 166 (19%) resolved completely; three of 166 (2%) thrombosed; and five 166 (3%) were repaired surgically. Another four of 166 (2%) underwent late surgery (0.5-5.0 years later). During the course of surveillance, none of the nonoperated false aneurysms associated with spontaneous ICAD gave rise to any new neurological or compressive symptoms. CONCLUSIONS: In this systematic review, >95% of nonoperated false aneurysms affecting the distal internal carotid artery that developed after an ICAD did not increase in size and were not associated with any delayed neurological symptoms suggesting that conservative management and serial surveillance is the optimal mode of treatment. As nearly all studies suffered from serious bias, reporting standards for diagnosis and follow-up are needed in order to better define their natural history.

Editor's Choice - Delays to Surgery and Procedural Risks Following Carotid Endarterectomy in the UK National Vascular Registry.

OBJECTIVE: Guidelines recommend that patients suffering an ischaemic transient ischaemic attack (TIA) or stroke caused by carotid artery stenosis should undergo carotid endarterectomy (CEA) within 14 days. METHOD: The degree to which UK vascular units met this standard was examined and whether rapid interventions were associated with procedural risks. The study analysed patients undergoing CEA between January 2009 and December 2014 from 100 UK NHS hospitals. Data were collected on patient characteristics, intervals of time from symptoms to surgery, and 30-day postoperative outcomes. The relationship between outcomes and time from symptom to surgery was evaluated using multilevel multivariable logistic regression. RESULTS: In 23,235 patients, the median time from TIA/stroke to CEA decreased over time, from 22 days (IQR 10-56) in 2009 to 12 days (IQR 7-26) in 2014. The proportion of patients treated within 14 days increased from 37% to 58%. This improvement was produced by shorter times across the care pathway: symptoms to referral, from medical review to being seen by a vascular surgeon, and then to surgery. The spread of the median time from symptom to surgery among NHS hospitals shrank between 2009 and 2013 but then grew slightly. Low-, medium-, and high-volume NHS hospitals all improved their performance similarly. Performing CEA within 48 h of symptom onset was associated with a small increase in the 30-day stroke and death rate: 3.1% (0-2 days) compared with 2.0% (3-7 days); adjusted odds ratio 1.64 (95% CI 1.04-2.59) but not with longer delays. CONCLUSIONS: The delay from symptom to CEA in symptomatic patients with ipsilateral 50-99% carotid stenoses has reduced substantially, although 42% of patients underwent CEA after the recommended 14 days. The risk of stroke after CEA was low, but there may be a small increase in risk during the first 48 h after symptoms.

Late Survival in Nonoperated Patients with Infrarenal Abdominal Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Historical studies report high rupture rates in patients with nonoperated abdominal aortic aneurysms (AAAs) of > 5.5 cm diameter, although a recent audit has questioned this. METHODS: This was a retrospective review of 138/764 (18%) patients with AAAs evaluated in a preassessment anaesthetic clinic (PAC) between 2006 and 2012, who either did not undergo elective AAA repair or who underwent deferred repair. The remaining 626 underwent repair. Patients with severe comorbidities (dementia, advanced malignancy, life-expectancy < 1 year) and not referred to PAC were excluded. RESULTS: At a median of 27 months, 71 (52%) died, 36 (51%) following rupture. Cumulative survival, free from rupture or surgery for acute symptoms, was 96% at 1 year, 84% at 3 years, and 64% at 5 years, where baseline AAA diameters were 5.5-6.9 cm. For diameters ≥ 7 cm, survival, free from rupture, was 65% at 1 year, 29% at 3 years, and 0% at 5 years. Median interval to rupture was 47 months (AAA diameter 5.5-6.9 cm) and 21 months where baseline diameters were ≥ 7 cm. Rupture accounted for 32% of late deaths in patients with AAAs of 5.5-5.9 cm diameter, 46% in those with AAAs measuring 6.0-6.9 cm in diameter, and 71% in patients with AAA measuring ≥ 7 cm in diameter. CONCLUSION: Approximately half of all late deaths in this nonoperated cohort were not AAA related, suggesting that even had repair been undertaken, it would not have prolonged patient survival. The incidence of rupture in "high-risk" patients with an AAA < 7 cm diameter was < 5% at 1 year, thereby giving ample time to optimise risk factors and improve pre-existing medical conditions prior to undertaking a deferred intervention. Even if these patients did not undergo surgical repair, the risk of late rupture was relatively low. By contrast, nonoperated patients with AAAs ≥ 7 cm in diameter face a very high risk of rupture and will probably benefit from elective surgery, with the caveat that a higher procedural risk might have to be incurred.

Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in Unstable Carotid Atherosclerotic Plaques.

OBJECTIVE/BACKGROUND: The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level. METHODS: Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort. RESULTS: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p < .001). Cathepsin G expression was upregulated in histologically unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p = .03). CCL19 also co-localised with CD3+ T-cell lymphocytes in the core region, around where CCL19 was expressed. CONCLUSIONS: CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated.

Clinical and imaging features associated with an increased risk of early and late stroke in patients with symptomatic carotid disease.

OBJECTIVE: The aim of this review was to identify clinical and/or imaging parameters that are associated with an increased (decreased) risk of early/late stroke in patients with symptomatic carotid disease. IN THE FIRST 14 DAYS: Natural history studies suggest that 8-15% of patients with 50-99% stenoses will suffer a stroke within 72 hours of their index symptom. Currently, there are insufficient validated data to identify highest-risk patients for emergency carotid endarterectomy (CEA), but an increased risk of stroke appears to be predicted by (i) an ABCD(2) score of 4-7; (ii) the presence of acute cerebral injury on CT/MRI; (iii) Gray Scale Median (GSM) <15, (iv) spontaneous embolisation on Transcranial Doppler (TCD); and (v) increased fluorodeoxyglucose (FDG) uptake in the carotid plaque on positron emission tomography (PET). A future goal must be to develop predictive algorithms (based on accessible imaging strategies) for identifying acutely symptomatic patients with highly unstable plaques for emergency CEA. MEDIUM TO LONG TERM: In the randomised trials, about 70% of patients with symptomatic 70-99% stenoses were stroke-free on "best medical therapy" at 5 years. Clinical predictors of increased stroke risk include (i) male gender; (ii) age >75; (iii) hemispheric symptoms; and (iv) increasing comorbidity. Imaging features associated with increased stroke risk include (i) irregular stenoses; (ii) contralateral occlusion; (iii) increasing stenosis severity, but not subocclusion; (iv) tandem intracranial disease; (v) a failure to recruit intracranial collaterals; (vi) low GSM; (vii) MR diagnosis of intra-plaque haemorrhage; (vii) spontaneous embolisation on TCD; and (viii) increased FDG uptake in the carotid plaque on PET. Clinical/imaging parameters associated with a lower risk of stroke include (i) female gender, especially those with 50-99% stenoses; (ii) ocular symptoms/lacunar stroke; (iii) smooth stenoses; and (iv) chronic subocclusion.

Dual Antiplatelet Therapy Prior to Expedited Carotid Surgery Reduces Recurrent Events Prior to Surgery without Significantly Increasing Peri-operative Bleeding Complications.

OBJECTIVE: A daily Rapid-Access TIA Clinic was introduced in 2008, where symptomatic patients were started on 75 mg aspirin + 40 mg simvastatin by the referring doctor, before attending the clinic. Following clinic assessment, patients with 50-99% stenoses were transferred to the vascular unit for carotid endarterectomy (CEA). In two audits (n = 212 patients), the median delay from transfer to the vascular unit to undergoing CEA was 3 days, during which time 28 patients (13%) suffered recurrent neurological events. It was hypothesized that early introduction of dual antiplatelet therapy (by adding clopidogrel 75 mg once parenchymal haemorrhage was excluded in the TIA clinic) might significantly reduce recurrent events between transfer to the surgical unit and undergoing CEA. METHODS: Prospective audit in 100 consecutive, recently symptomatic patients receiving dual antiplatelet therapy. Endpoints were: prevalence of recurrent events between transfer from the TIA clinic and undergoing CEA; rates of spontaneous embolization prior to undergoing CEA; and prevalence of haemorrhagic complications RESULTS: The median delay from symptom to CEA was 8 days (IQR 5-15). The median delay between transfer from the TIA clinic to CEA was 3 days (IQR 2-5), during which time three patients (3%) suffered recurrent TIAs. This represents a fivefold reduction compared with previous audit data (OR 4.9, 95% CI 1.5-16.6, p = .01) and was matched by a fourfold reduction in the prevalence of spontaneous embolization from 39/189 (21%) previously to 5/83 (5%) in the current audit (OR 4.1, 95% CI 1.5-10.7, p = .0047). The 30-day death/stroke rate was 1%. There were three haemorrhagic complications: stroke caused by haemorrhagic transformation of an infarct; exploration for neck haematoma; and debridement and skin grafting for spontaneous shin haematoma. CONCLUSION: Early introduction of dual antiplatelet therapy was associated with a significant reduction in recurrent neurological events and spontaneous embolization prior to CEA, without incurring a significant increase in major peri-operative bleeding complications.

Long-term Mortality in Patients with Asymptomatic Carotid Stenosis: Implications for Statin Therapy.

OBJECTIVE: Recent studies with asymptomatic carotid patients on best medical management have shown that the annual risk of stroke has decreased to approximately 1%. There is no evidence that a similar decrease in mortality has occurred. In addition, the intensity of statin therapy for these patients has not yet been determined. The aims of this review were to determine (a) the reported long-term all-cause and cardiac-related mortality in patients with asymptomatic carotid stenosis (ACS) > 50%, (b) whether there has been a decrease in mortality in recent years, (c) the available methods of mortality risk stratification, and (d) whether the latest ACC/AHA guidelines on the treatment of serum lipids can be applied to this group of patients. METHODS: Systematic review of PubMed, EuroPubMed, and Cochrane Library and meta-analysis using random effects for pooled proportions were performed regarding long-term all-cause and cardiac-related mortality and the associated risk factors in ACS patients. The last day for literature search was October 30, 2014. RESULTS: Seventeen studies were retrieved reporting 5-year all-cause mortality in 11,391 patients with ACS >50%. The 5-year cumulative all-cause mortality across all 17 studies was 23.6% (95% CI 20.50-26.80). Twelve additional studies, reporting both all-cause and cardiac mortality with a minimum of 2 year follow-up and involving 4,072 patients were identified. Of the 930 deaths reported, 589 (62.9%; 95% CI 58.81-66.89) were cardiac-related. This translates into an average cardiac-related mortality of 2.9% per year. CONCLUSIONS: All-cause and cardiac mortality in ACS patients are very high. Although risk stratification is possible, most patients are classified as high risk. In view of this high risk, aggressive statin therapy is indicated if the new ACC/AHA guidelines on serum lipids are to be adhered to.

A Novel Ultrasound-Based Carotid Plaque Risk Index Associated with the Presence of Cerebrovascular Symptoms.

PURPOSE: The purpose of this study was to determine the efficacy of a novel ultrasound-based carotid plaque risk index (CPRI) in predicting the presence of cerebrovascular symptoms in patients with carotid artery stenosis. MATERIALS AND METHODS: This was a cross-sectional, observational study involving 56 patients (mean age 76.6 years, 62.5 % male). Plaque grayscale median (GSM) and surface irregularity indices (SII) were measured in 82 stenosed carotid arteries (range 10 - 95 %) and combined with the degree of stenosis (DOS) in the form of (DOS*SII)/(1 + GSM). A reduced index DOS/(1 + GSM) not incorporating plaque surface irregularities was also investigated. Receiver operating characteristic curves (ROC) were used to study the diagnostic efficacy of CPRI, comparing against DOS and an equivalent risk index constructed using a conventional logistic regression based method with model parameters optimized to the dataset (CPRIlogistic). RESULTS: There were 42 stenosed carotid arteries with cerebrovascular symptoms, and 40 without symptoms. The presence of symptoms significantly correlated with DOS, GSM and SII (p < 0.01). The median CPRI of the symptomatic (asymptomatic) groups were 23.2 (9.2) compared with 0.71 (0.30) for CPRIlogistic (p < 0.01). The diagnostic performance of CPRI exceeded that of CPRIlogistic and DOS, and demonstrated a better separation of the symptomatic and asymptomatic groups. CONCLUSION: Our novel risk index combines quantitative measures of carotid plaque echogenicity and surface irregularities with the degree of stenosis. It is a better predictor of cerebrovascular symptoms than the degree of stenosis and could be valuable in studies and clinical trials aimed at identifying vulnerable carotid artery stenoses.

Clinical and imaging features associated with an increased risk of late stroke in patients with asymptomatic carotid disease.

BACKGROUND: The 2011 American Heart Association Guidelines on the management of asymptomatic carotid disease recommends that carotid endarterectomy (CEA) (with carotid artery stenting (CAS) as an alternative) may be considered in highly selected patients with 70-99% stenoses. However, no guidance was provided as to what "highly selected" meant. This caveat is, however, important as up to 95% of asymptomatic individuals undergoing prophylactic CEA or CAS will ultimately undergo an unnecessary procedure. Even if the procedural risk following CEA or CAS could be reduced to 0%; 93% of patients would still undergo an unnecessary intervention. This, coupled with growing awareness that the risk of stroke in medically treated patients appears to be diminishing, has led to a renewed drive towards identifying patients with the highest risk of suffering a stroke whilst on medical therapy in whom to target CEA/CAS. METHODS: Review of clinical and/or imaging based scoring systems, predictive algorithms and imaging parameters that may be associated with an increased (or decreased) risk of stroke in patients with asymptomatic carotid disease. RESULTS: Parameters associated with an increased risk of late stroke include: (a) silent infarction on CT/MRI; (b) stenosis progression; (c) hypoechoic plaques or GSM <15; (d) irregular plaques; (e) evidence of spontaneous embolization on TCD; (f) AHA plaque types IV-V, VI; (g) MR diagnosed IPH; (h) plaque area >80 mm(2); (i) juxta-luminal black area >10 mm(2); and (j) tandem intracranial disease. CONCLUSIONS: A number of imaging parameters have been shown to be predictive of an increased risk of late stroke in previously asymptomatic patients. None have been independently validated, but many could easily be evaluated in natural history studies or randomized trials in order to identify a "high risk for stroke" cohort in whom CEA/CAS could be prioritized.

Identification of patients with a histologically unstable carotid plaque using ultrasonic plaque image analysis.

OBJECTIVES: In patients with carotid stenosis the risk of stroke is highest in the first few days after onset of symptoms and it is low in asymptomatic patients. The ability to identify patients with a high (or low) probability of having a histologically unstable plaque might become a complimentary method that can refine the indications for surgical intervention. METHODS: Two histopathologists, using validated American Heart Association criteria, independently graded plaques harvested during carotid endarterectomy. Preoperative Duplex images were independently assessed for juxtaluminal black area, plaque type, plaque area, and grey-scale median (GSM) following image normalization. Logistic regression analysis was then performed to create a model for predicting predominantly histologically unstable or stable plaques. RESULTS: A total of 126 patients were included in the study. Based on the presence and extent of histological features including haemorrhage, thrombus, fibrous tissue, lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques were graded as predominantly stable, while 87 were predominantly unstable. Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI 1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to 6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression indicated that patients with the first two features had a 90% probability of having a histologically unstable plaque. The model was used to calculate the probability of having an unstable plaque in each patient. The receiver operating characteristic curve using the p value was 0.68 (95% CI 0.59-0.78). CONCLUSIONS: Computerized plaque analysis has the potential to identify patients with histologically unstable carotid plaques. This model requires validation, but offers the potential to influence patient selection for emergency interventions and the monitoring of medical therapy.

Delay prior to expedited carotid endarterectomy: a prospective audit of practice.

OBJECTIVES: To identify reasons for delay before carotid endarterectomy (CEA) in a reconfigured "fast-track" system where patients were admitted from the TIA (transient ischaemic attack) Clinic for urgent CEA. METHODS: Prospective audit in 89 recently symptomatic patients. RESULTS: Ten patients (11%) suffered recurrent symptoms between admission and surgery. Two strokes were sufficiently severe that CEA was cancelled. The median delay from index symptom to CEA was 8 days. 74/87 (85%) underwent CEA <14 days from the index symptom; 39/87 (45%) within 7 days. Forty-five (51%) were ready for CEA <24 hours of admission; 74 (83%) <72 hours. The most common reasons for delay to CEA were logistical, especially a failure to plan for access to weekend operating. Two-thirds of the Tuesday/Friday theatre lists that were reserved for urgent CEAs were actually used for CEA; 27 (33%) were not used for CEA but were utilized for another vascular procedure, and five (4%) were cancelled the day before and went unused. CONCLUSIONS: The vast majority of patients (85%) underwent CEA <14 days from the index symptom, but 11% still suffered recurrent symptoms prior to surgery. Transferring patients directly from the TIA Clinic reduced overall delays, but Vascular Units adopting such an approach might then be vulnerable to criticisms regarding prolonged lengths of pre-operative in-patient stay while patients were worked up for theatre. Protected theatre lists both optimized (and delayed) access to CEA, but the most important cause of delay was that we had not planned for weekend operating using specialist anaesthetic and theatre staff.

Changes in middle cerebral artery velocity after carotid endarterectomy do not identify patients at high-risk of suffering intracranial haemorrhage or stroke due to hyperperfusion syndrome.

OBJECTIVES: To determine if significant increases in middle cerebral artery velocity (MCAV) or pulsatility index (PI) during and immediately after carotid endarterectomy (CEA) were predictive of patients suffering a stroke due to the hyperperfusion syndrome (HS) or intracerebral haemorrhage (ICH). METHODS: Transcranial Doppler (TCD) mean/peak MCAV and PI were recorded pre-operatively; pre-clamp; 1-min post-declamping; 10-min post-declamping and 30-min post-operatively. The study was divided into two time periods; Group 1 (1995-2007); where there was no formal guidance for managing post-CEA hypertension (PEH) and Group 2 (2008-2012); where written guidelines for treating PEH were available. RESULTS: 11/1024 patients in Group 1 (1.1%) suffered a stroke due to HS/ICH, compared to 0/426 patients (0.0%) in Group 2 (p = 0.02). In Group 1; intra-operative increases >100% in mean/peak MCAV and PI at 1 and 10-min post-clamp release had positive predictive values (PPV) of 1.2%, 6.3% and 20.0% and 2.9%, 8.0% and 16.6% respectively. Post-operatively; a >100% increase in mean and peak MCAV had a PPV of 6.3% and 2.7% respectively. CONCLUSION: We were unable to demonstrate that significant increases in MCAV and PI were able to predict patients at increased risk of suffering a post-operative stroke due to HS or ICH. The provision of written guidance for managing PEH in Group 2 patients was associated with virtual abolition of ICH/HS.

Features of unstable carotid plaque during and after the hyperacute period following TIA/stroke.

BACKGROUND: The aim was to test the hypothesis that histologically unstable carotid plaque features were more prevalent in patients undergoing carotid endarterectomy (CEA) in the acute period after onset of symptoms and that the plaque would assume more stable histological characteristics as the delay from the most recent event increased. METHODS: Seven histological features of plaque instability (haemorrhage, large lipid core, chronic plaque inflammation, chronic cap inflammation, marked vascularity, cap rupture and many foam cells) were independently quantified and then correlated with recency of symptoms in patients undergoing CEA. RESULTS: In patients undergoing CEA ≤14 days of their last event, 87/119 (73%) exhibited ≥5/7 unstable histological plaque features, compared with 22/40 (55%) of patients undergoing delayed surgery (P = 0.048). As expected, there was a sustained decline in the prevalence of unstable plaque features in 61 patients undergoing surgery between days 7-28. However, there was then a marked increase in the prevalence of plaque haemorrhage (59% up to 65%), large lipid core (41% up to 78%), chronic plaque inflammation (71% up to 91%), cap rupture (35% up to 39%), many foam cells (24% up to 43%) and marked vascularity (71% up to 91%) in 23 patients undergoing CEA after 29 days had elapsed. CONCLUSION: Patients undergoing surgery ≤14 days had a significantly higher overall burden of high risk plaque features compared with those undergoing delayed CEA. However, the secondary upsurge across a range of unstable plaque features in patients undergoing CEA after ≥29 days had elapsed suggests that the relationship between recency of symptoms and plaque histology is more complex than had been anticipated in previous studies.

Histologically unstable asymptomatic carotid plaques have altered expression of genes involved in chemokine signalling leading to localised plaque inflammation and rupture.

BACKGROUND: Many studies have evaluated histological and gene expression profiles in TIA/stroke patients after onset of symptoms, but there is limited understanding as to how these plaque related features interact before symptom onset. In particular, no studies have evaluated differential gene expression in histologically unstable (vs stable plaques) in neurologically asymptomatic patients. METHODS: Nine asymptomatic patients had their plaques scored blindly by two independent Histopathologists using the AHA plaque scoring system. RNA extracted from the plaques was hybridised onto a whole genome microarray. Analysis was performed using GenomeStudio (v1.0) and the DAVID bioinformatics resource (v6.7). RESULTS: Three plaques were histologically unstable (Grade 2/3), while six were stable (Grade 0/1). 346 differentially expressed genes (>1.3 fold, P < 0.05) were identified (293 down-regulated and 53 up-regulated) between stable and unstable plaques. Genes related to chemokine and protein signalling (pro-inflammatory/pro-apoptotic) were identified to have high enrichment scores (>1.3) and were significantly up-regulated in unstable (asymptomatic) plaques. CONCLUSION: The findings confirm the intuitively held belief that changes in chemokine and protein signalling may be associated with acute plaque disruption and precede the onset of symptoms. Once validated, these genes could therefore become targets for innovative medical treatments in the future or could help identify asymptomatic patients with histologically unstable plaques that would benefit from surgical intervention.