The 2nd European Carotid Surgery Trial (ECST-2): rationale and protocol for a randomised clinical trial comparing immediate revascularisation versus optimised medical therapy alone in patients with symptomatic and asymptomatic carotid stenosis at low to intermediate risk of stroke.

BACKGROUND: Carotid endarterectomy is currently recommended for patients with recently symptomatic carotid stenosis ≥50%, based on randomised trials conducted 30 years ago. Several factors such as carotid plaque ulceration, age and associated comorbidities might influence the risk-benefit ratio of carotid revascularisation. A model developed in previous trials that calculates the future risk of stroke based on these features can be used to stratify patients into low, intermediate or high risk. Since the original trials, medical treatment has improved significantly. Our hypothesis is that patients with carotid stenosis ≥50% associated with a low to intermediate risk of stroke will not benefit from additional carotid revascularisation when treated with optimised medical therapy. We also hypothesise that prediction of future risk of stroke in individual patients with carotid stenosis can be improved using the results of magnetic resonance imaging (MRI) of the carotid plaque. METHODS: Patients are randomised between immediate revascularisation plus OMT versus OMT alone. Suitable patients are those with asymptomatic or symptomatic carotid stenosis ≥50% with an estimated 5-year risk of stroke of <20%, as calculated using the Carotid Artery Risk score. MRI of the brain at baseline and during follow-up will be used as a blinded measure to assess the incidence of silent infarction and haemorrhage, while carotid plaque MRI at baseline will be used to investigate the hypotheses that plaque characteristics determine future stroke risk and help identify a subgroup of patients that will benefit from revascularisation. An initial analysis will be conducted after recruitment of 320 patients with baseline MRI and a minimum of 2 years of follow-up, to provide data to inform the design and sample size for a continuation or re-launch of the study. The primary outcome measure of this initial analysis is the combined 2-year rate of any clinically manifest stroke, new cerebral infarct on MRI, myocardial infarction or periprocedural death. DISCUSSION: ECST-2 will provide new data on the efficacy of modern optimal medical therapy alone versus added carotid revascularisation in patients with carotid stenosis at low to intermediate risk of future stroke selected by individualised risk assessment. We anticipate that the results of baseline brain and carotid plaque MRI will provide data to improve the prediction of the risk of stroke and the effect of treatment in patients with carotid stenosis. TRIAL REGISTRATION: ISRCTN registry ISRCTN97744893 . Registered on 05 July 2012.

Arterial Spin Labeling MRI in Carotid Stenosis: Arterial Transit Artifacts May Predict Symptoms.

BackgroundStenosis of the internal carotid artery has a higher risk for stroke. Many investigations have focused on structure and plaque composition as signs of plaque vulnerability, but few studies have analyzed hemodynamic changes in the brain as a risk factor.PurposeTo use 3-T MRI methods including contrast material-enhanced MR angiography, carotid plaque imaging, and arterial spin labeling (ASL) to identify imaging parameters that best help distinguish between asymptomatic and symptomatic participants with carotid stenosis.Materials and MethodsParticipants with carotid stenosis from two ongoing prospective studies who underwent ASL and carotid plaque imaging with use of 3-T MRI in the same setting from 2014 to 2018 were studied. Participants were assessed clinically for recent symptoms (transient ischemic attack or stroke) and divided equally into symptomatic and nonsymptomatic groups. Reviewers were blinded to the symptomatic status and MRI scans were analyzed for the degree of stenosis, plaque surface structure, presence of intraplaque hemorrhage (IPH), circle of Willis collaterals, and the presence and severity of arterial transit artifacts (ATAs) at ASL imaging. MRI findings were correlated with symptomatic status by using t tests and the Fisher exact test.ResultsA total of 44 participants (mean age, 71 years ± 10 [standard deviation]; 31 men) were evaluated. ATAs were seen only in participants with greater than 70% stenosis (16 of 28 patients; P < .001) and were associated with absence of anterior communicating artery (13 of 16 patients; P = .003). There was no association between history of symptoms and degree of stenosis (27 patients with ≥70% stenosis and 17 patients with <70%; P = .54), IPH (12 patients with IPH and 32 patients without IPH; P = .31), and plaque surface structure (17 patients with irregular or ulcerated plaque and 27 with smooth plaque; P = .54). Participants with ATAs (n = 16) were more likely to be symptomatic than were those without ATAs (n = 28) (P = .004). Symptomatic status also was associated with the severity of ATAs (P = .002).ConclusionArterial transit artifacts were the only factor associated with recent ischemic symptoms in participants with carotid stenosis. The degree of stenosis, plaque ulceration, and intraplaque hemorrhage were not associated with symptomatic status.© RSNA, 2020Online supplemental material is available for this article.See also the editorial by Zaharchuk in this issue.

Atrial Fibrillation: An Underestimated Cause of Ischemic Monocular Visual Loss?

INTRODUCTION: Atrial fibrillation (AF) is a major cause of ischemic stroke and Transient Ischemic Attack (TIA) and investigation for paroxysmal AF is recommended following an embolic brain event. In contrast, retinal ischemic monocular blindness is traditionally considered most linked to carotid artery disease (CAS) and investigating for AF is less vigilant. We aimed to determine the prevalence of AF in patients with ischemic monocular blindness. METHODS: Consecutive records of all patients presenting to a daily TIA clinic with transient or permanent ischemic monocular blindness were reviewed, January 2014-October 2016. RESULTS: Of 400 patients, 224 (56.0%) were male, mean age 64.5 years (SD 15.1). A total of 263 (66%) presented with transient and 137 (34%) with permanent ischemic monocular blindness. ECG was performed in 364 patients (91%) but only 211 (52%) had further cardiac monitoring. The vast majority (97.3%) had carotid imaging. Thirty-six patients (9%) were found to have AF while 53 (14%) had ipsilateral CAS. Median ABCD2 score was 1 in AF and non-AF groups. Only 55% of known AF patients were anticoagulated at presentation, despite all having CHADVASC2 score greater than or equal to 1. Patients with AF had more hypertension (P = .004), previous TIA (P = .002), previous stroke (P = .044) and ischemic heart disease (P = .022) with no difference in age (P = .791), diabetes (P = .563), smoking (P = .460) nor hypercholesterolaemia (P = .083). CONCLUSIONS: A total of 9% of patients with ischemic monocular blindness had AF. This is an underestimate, as only 53% of patients had prolonged cardiac monitoring. Known AF was suboptimally managed with only 55% receiving anticoagulation despite being eligible.

Undertreatment of Vascular Risk Factors in Patients with Monocular Ischaemic Visual Loss.

BACKGROUND AND PURPOSE: Ischaemic visual loss is often considered a lower risk factor than other transient ischaemic attacks (TIA). We aimed to determine the recurrence risk, prevalence and management of vascular risk factors in these patients. METHODS: The study took place in the University College Hospital London daily TIA clinic, main referral centre for North-Central London and Moorfields Eye Hospital. Consecutive records for patients with transient (< 24 h) or permanent (> 24 h) ischaemic visual loss were reviewed during the period January 2014-October 2016. Patients diagnosed with temporal arteritis were excluded. RESULTS: Of 400 patients, 224 (56%) were male with mean age 64.5 years (SD 15.1); 263 patients (65.8%) presented with transient and 137 patients (34.2%) with permanent ischaemic visual loss; 51.3% had hypertension (HTN), 35.3% hypercholesterolaemia, 14.5% diabetes, 11.8% ischaemic ocular events, 10.0% ischaemic heart disease, 7.3% atrial fibrillation (AF), 6.3% TIA, 5.3% stroke, and 12.3% were smokers. Median vascular risk factors were 2 (range 1-6), but 122 (30.5%) had ≥3. Those with diabetes (p < 0.001), HTN (p = 0.008), previous myocardial infarction (p = 0.005), or ≥3 vascular risk factors (p = 0.012) were more likely to present with permanent visual loss, while patients with history of transient events, TIA (p = 0.002), or ocular (p = 0.002) presented with transient visual loss. Ninety-day recurrence was 10.5%; this was higher in patients with ≥3 risk factors (hazard ratio 1.42, 95% CI 0.95-2.11, p = 0.111). Patients with past TIA were more likely to be on secondary prevention than those with ocular ischaemia; 60.0 vs. 34.1% received antiplatelets and 76.0 vs. 43.9% statins. At presentation, only 55.2% (16 patients) with known AF were anticoagulated, despite all of them having CHADSVASC ≥1. CONCLUSIONS: Approximately one-third of patients with ocular ischaemia had ≥3 vascular risk factors with recurrences higher in these patients. Yet only half of those with previous ischaemic ocular events were on antiplatelets or statins. These patients should be investigated and treated as aggressively as other forms of TIA or stroke.