Ankur Thapar

Hypertension and the post-carotid endarterectomy cerebral hyperperfusion syndrome.

OBJECTIVE Cerebral hyperperfusion syndrome is a preventable cause of stroke after carotid endarterectomy (CEA). It manifests as headache, seizures, hemiparesis or coma due to raised intracranial pressure or intracerebral haemorrhage (ICH). There is currently no consensus on whether to control blood pressure, blood pressure thresholds associated with cerebral hyperperfusion syndrome, choice of anti-hypertensive agent(s) or duration of treatment. METHOD A systematic review of the PubMed database (1963-2010) was performed using appropriate search terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS A total of 36 studies were identified as fitting a priori inclusion criteria. Following CEA, the incidence of severe hypertension was 19%, that of cerebral hyperperfusion 1% and ICH 0.5%. The postoperative mean systolic blood pressure of patients, who went on to develop cerebral hyperperfusion syndrome, was 164 mmHg (95% confidence interval (CI) 150-178 mmHg) and the cumulative incidence of cases rose appreciably above a postoperative systolic blood pressure of 150 mmHg. The mean systolic blood pressure of cerebral hyperperfusion cases was 189 mmHg (95% CI 183-196 mmHg) at presentation. The incidence of cerebral hyperperfusion in the first week was 92% with a median time to presentation of 5 days (interquartile range (IQR) 3-6 days). 36% of patients presented with seizures 31% with hemiparesis and 33% with both. The proportion of patients with severe hypertension was significantly higher in cases than in post-CEA controls (p < 0.0001, Odds ratio 19 (95% CI 9-41)). Three large case-control studies identify postoperative hypertension as a risk factor for ICH. CONCLUSION There is currently level-3 evidence for the prevention of ICH through control of postoperative blood pressure. From the available data, we suggest a definition for cerebral hyperperfusion syndrome, blood pressure thresholds, duration of monitoring and a postoperative blood pressure control strategy for validation in a prospective study. The implications of this are that one in five patients would need intravenous anti-hypertensives and home blood pressure monitoring for 1 week.

Why Calls for More Routine Carotid Stenting Are Currently Inappropriate: An International, Multispecialty, Expert Review and Position Statement

Why Calls for More Routine Carotid Stenting Are Currently Inappropriate An International, Multispecialty, Expert Review and Position Statement

Dose-Dependent Artifact in the Far Wall of the Carotid Artery at Dynamic Contrast-enhanced US

PURPOSE To quantify a pseudoenhancement phenomenon observed during dynamic contrast material-enhanced ultrasonography (US) of the carotid artery, both in vitro and in vivo. MATERIALS AND METHODS Ethical approval was obtained prior to commencing this prospective case series, and each patient gave written informed consent. Thirty-one patients with 50%-99% internal carotid artery stenosis underwent dynamic contrast-enhanced US of the carotid bifurcation with use of 2 mL of microbubbles. In the final 10 patients, an additional 1 mL bolus was administered after 15 minutes. Raw linear digital imaging and communications in medicine data were analyzed offline. Regions of interest were drawn within the common carotid artery lumen and immediately adjacent to the lumen in the near and far wall adventitia. Peak intensity was measured. An in vitro experiment with a single-channel flow phantom was also performed. This apparatus consisted of an 8-mm-diameter latex tube placed in a tissue-mimicking fluid. Microbubble concentrations of 0.02%, 0.1%, 0.5%, 1%, and 2% were pumped into the tube. Regions of interest were drawn in a similar fashion to the in vivo experiments, and peak intensity was measured. The Wilcoxon signed rank and paired t tests were used to compare the difference between the near and far wall signal intensities at each dose; a multiplication factor comparing near and far wall signal intensity was derived. RESULTS The far wall of the common carotid artery was significantly more echogenic than the near wall at 2 mL contrast agent doses (P<.0001, n=31), and the far wall signal intensity increased synchronously with that of the lumen. The difference in signal intensity between near and far wall regions was significantly greater at 2 mL than at 1 mL (P=.012, n=10). In vitro, the phantom tubing demonstrated a similar pattern and magnitude of enhancement to that seen in vivo. CONCLUSION A dose-dependent, nonlinear propagation artifact known as pseudoenhancement occurs in the far wall adventitia of the carotid artery and should not be mistaken as a marker of plaque vulnerability.

Silent cerebral events in asymptomatic carotid stenosis.

BACKGROUND Approximately 20% of strokes are attributable to carotid stenosis. However, the number of asymptomatic patients needed to prevent one stroke or death with endarterectomy is high at 17 to 32. There is a clear need to identify asymptomatic individuals at high risk of developing future ischemic events to improve the cost-effectiveness of surgery. Our aim was to examine the evidence for subclinical microembolization and silent brain infarction in the prediction of stroke in asymptomatic carotid stenosis using transcranial Doppler (TCD), computed tomography (CT), and magnetic resonance imaging (MRI). METHODS The review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Articles regarding humans between 1966 and 2010 were identified through systematic searches of Pubmed, MEDLINE, and EMBASE electronic databases using a predetermined search algorithm. RESULTS Fifty-eight full text articles met the inclusion criteria. A median of 28% of microemboli positive patients experienced a stroke or transient ischemic attack during follow-up compared with 2% of microemboli negative patients (P = .001). The same was true for the end point of stroke alone with a median of 10% of microemboli positive patients experiencing a stroke vs 1% of microemboli negative patients (P = .004). A specific pattern of silent CT infarctions was related to future stroke risk (odds ratio [OR] = 4.6; confidence interval [CI] = 3.0-7.2; P < .0001). There are no prospective MRI studies linking silent infarction and stroke risk. CONCLUSIONS There is level 1 evidence for the use of TCD to detect microembolization as a risk stratification tool. However, this technique requires further investigation as a stroke prevention tool and would be complemented by improvements in carotid plaque imaging.

Hypoxia-Inducible Factor-1 in Arterial Disease: A Putative Therapeutic Target

Hypoxia-inducible factor-1 (HIF-1) is a nuclear transcription factor that is upregulated in hypoxia and co-ordinates the adaptive response to hypoxia by driving the expression of over 100 genes. In facilitating tissues to adapt to hypoxia, HIF-1 may have a role in reducing the cellular damage induced by ischaemia, such as that seen in peripheral arterial disease (PAD), or following acute ischaemic insults such as stroke and myocardial infarction. This therefore raises the possibility of HIF-1 modulation in such contexts to reduce the consequences of ischaemic injury. HIF1 has further been implicated in the pathogenesis of atherosclerosis, abdominal aortic aneurysm (AAA) formation, pulmonary hypertension and systemic hypertension associated with obstructive sleep apnoea. Through a better understanding of the role of HIF-1 in these disease processes, novel treatments which target HIF-1 pathway may be considered. This review summarises the role of HIF-1 in arterial disease, specifically its role in atherosclerosis, ischaemic heart disease, in-stent restenosis following coronary revascularisation, stroke, PAD, AAA formation, pulmonary artery hypertension and systemic hypertension. The potential for exploiting the HIF-1 signalling pathway in developing therapeutics for these conditions is discussed, including progress made so far, with attention given to studies looking into the use of prolyl-hydroxylase inhibitors.

Temporal trends in safety of carotid endarterectomy in asymptomatic patients

Objective: To systematically review temporal changes in perioperative safety of carotid endarterectomy (CEA) in asymptomatic individuals in trial and registry studies. Methods: The MEDLINE and EMBASE databases were searched using the terms “carotid” and “endarterectomy” and “asymptomatic” from 1947 to August 23, 2014. Articles dealing with 50%–99% stenosis in asymptomatic individuals were included and low-volume studies were excluded. The primary endpoint was 30-day stroke or death and the secondary endpoint was 30-day all-cause mortality. Statistical analysis was performed using random-effects meta-regression for registry data and for trial data graphical interpretation alone was used. Results: Six trials (n = 4,431 procedures) and 47 community registries (n = 204,622 procedures) reported data between 1983 and 2013. Registry data showed a significant decrease in postoperative stroke or death incidence over the period 1991–2010, equivalent to a 6% average proportional annual reduction (95% credible interval [CrI] 4%–7%; p < 0.001). Considering postoperative all-cause mortality, registry data showed a significant 5% average proportional annual reduction (95% CrI 3%–9%; p < 0.001). Trial data showed a similar visual trend. Conclusions: CEA is safer than ever before and high-volume registry results closely mirror the results of trials. New benchmarks for CEA are a stroke or death risk of 1.2% and a mortality risk of 0.4%. This information will prove useful for quality improvement programs, for health care funders, and for those re-examining the long-term benefits of asymptomatic revascularization in future trials.

Late-Phase Contrast-Enhanced Ultrasound Reflects Biological Features of Instability in Human Carotid Atherosclerosis

Background and Purpose— Development of translational functional imaging modalities for atherosclerosis risk stratification is sought for stroke prediction. Our group has developed late-phase contrast-enhanced ultrasound (LP-CEUS) to quantify microbubble contrast retention within carotid atherosclerosis and shown it to separate asymptomatic plaques from those responsible for recent cerebrovascular events. We hypothesized that microbubbles are retained in areas of plaque inflammation, aiming to examine whether LP-CEUS signal reflects plaque biology. Methods— Subjects awaiting carotid endarterectomy (n=31) underwent axial LP-CEUS and diseased intimal segments were symmetrically divided in the long axis. Half-specimens underwent quantitative immunohistochemical analysis for CD68 (macrophages) and CD31 (angiogenesis). Half-specimens were processed for atheroma cell culture and supernatant collected at 24 hours for multianalyte profiling for 34 analytes. Results— Percentage area immunopositivity was significantly higher in subjects in which normalized plaque late-phase intensity was ≥0 versus <0 (CD68 mean 11.8 versus 6.68, P=0.004; CD31 mean 9.45 versus 4.82, P=0.025). Interleukin-6, matrix metalloproteinase-1, and matrix metalloproteinase-3 were significantly higher by multianalyte profiling when LP-CEUS was ≥0. Conclusions— LP-CEUS reflects biological features of inflammation and angiogenesis, key features predisposing to plaque rupture. Further investigation of LP-CEUS as a tissue-specific marker of inflammation for risk stratification of carotid atherosclerosis is warranted.

Systematic review of sonographic chronic cerebrospinal venous insufficiency findings in multiple sclerosis

Objective The sonographic findings of chronic cerebrospinal venous insufficiency (CCSVI) are used by some as selection criteria for venography. We performed a systematic review to establish the prevalence and strength of association between sonographic CCSVI and multiple sclerosis (MS). Method Two reviewers searched PubMed and EMBASE from 1948 to date using the keywords ‘chronic cerebrospinal venous insufficiency’ according to PRISMA guidelines. Results Four cross-sectional studies met the criteria for inclusion. The prevalence of CCSVI ranged from 7% to 100% in MS patients and from 2% to 36% in healthy controls. Diagnostic odds ratios for MS varied between 2 and 26, 499 (I 2 = 94%). Sensitivities of CCSVI for MS varied between 7% and 100% (I 2 = 98%). Specificities varied between 64% and 100% (I 2 = 95%). Conclusion There is substantial variation in the strength of association between CCSVI and MS beyond that explained by demographic differences or sonographer training. Reliable evidence on which to base decisions requires sonographic consensus and assessment of the reproducibility of individual criteria between trained sonographers.

The European burden of primary varicose veins.

Background: The treatment of varicose veins has been demonstrated to improve quality of life, alleviate symptoms of depression and treat the complications of venous disease. This study aims to show the studies which contain information regarding the prevalence and distribution of venous disease. Then using the population and prevalence data for venous disease, and considering the cost of treating varicose veins, this study aims to analyse the treatment of varicose veins and assess whether there is a disparity between European countries. Methods: Relevant papers regarding the prevalence or incidence of venous disease were identified through searches of PubMed (1966 to October 2010). The search terms ‘prevalence OR incidence’ AND ‘varicose veins or venous disease’ were used. Population data, prevalence data and the number of varicose vein procedures performed in each country was obtained for 2010. Results: Four studies were included. From calculated values comparing the predicted and actual number of patients requiring treatment for venous disease, the UK, Finland and Sweden are potentially not treating all patients with C2 disease. In contrast to this, all other European countries represented are treating more patients, suggesting that they may be treating additional patients. There was up to a four-fold difference in the numbers of procedures per million population that were performed for varicose veins in different European countries. Conclusion: There is a marked disparity across Europe between the predicted number of patients with varicose veins requiring treatment and the actual care given. The factors influencing this need more detailed investigation.

Internal jugular thrombosis post venoplasty for chronic cerebrospinal venous insufficiency.

Chronic cerebrospinal venous insufficiency (CCSVI) is a hypothesis through which cerebral venous drainage abnormalities contribute towards the pathogenesis of multiple sclerosis. CCSVI venoplasty is already practised worldwide. We report the case of a 33-year-old lady with multiple sclerosis who underwent left internal jugular venoplasty resulting in iatrogenic jugular thrombosis requiring open thrombectomy for symptom relief. This occurred without insertion of a stent and while fully anticoagulated. Clinicians should be aware that endovenous treatment of CCSVI could cause paradoxical deterioration of cerebral venous drainage. Patients with complications post venoplasty are now presenting to geographically distant vascular units.