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Urgent Carotid Intervention in Patients with Minor to Moderate Strokes (NIHSS < 10) Performed After 48 Hours Results in Greater Functional Independence at Discharge
Esther Mihindu, Alaa Mohammed, Bethany Jennings, Mustafa Alhasan, James Milburn, Taylor Smith, Clayton Brinster, WC Sternbergh III, Hernan Bazan
Ochsner Clinic Foundation, New Orleans, LA

Increasing evidence indicates suggests that urgent carotid intervention after transient ischemic attack (TIA) or non-disabling stroke is safe1. However, functional outcome following urgent carotid intervention for various degrees of stroke severity has not yet been quantified. We aimed to determine whether increased stroke severity on presentation is associated with poor functional outcomes in patients undergoing urgent carotid endarterectomy (CEA) or carotid artery stenting (CAS).
A total of 120 urgent interventions (96 CEA, 22 CAS, 1 CEA/intracranial thrombectomy, 1 carotid embolectomy) were performed from January 2013 thru April 2017 at a single, tertiary referral center. Urgent interventions were defined as CEA or CAS performed during the index hospitalization after presentation with a TIA or acute stroke in patients with >50% carotid stenosis. Elective carotid interventions for asymptomatic or symptomatic carotid stenosis were excluded. Carotid imaging encompassed a preoperative carotid ultrasound, computed tomography (CT) angiography, or magnetic resonance imaging of the head and neck. Patients presenting with acute strokes were evaluated with penumbra imaging. Admit National Institutes of Health Stroke Scale (NIHSS) and discharge modified Rankin scale (mRS) were calculated by vascular stroke neurologists.
Preoperative variables analyzed included patient demographics and comorbidities, including hypertension, hyperlipidemia, coronary artery disease, chronic kidney disease, defined as chronic kidney disease (CKD) stage III or higher, and history of tobacco use. Admit stroke severity was determined using NIHSS, which is a 15-item neurologic evaluation (score of < 4: minor stroke; 5-15: moderate stroke; 15-20: moderate/severe stroke; and 21-42: severe stroke), and the Alberta stroke program early
CT score (ASPECTS). ASPECTS is a 10-point quantitative topographic CT scan score in patients with stroke used to quantify size of stroke. One point is assigned to each region of the middle cerebral artery with a point deducted for each region involved.
The primary endpoint analyzed was patient functional independence at discharge, which was quantified using the mRS. The mRS measures the degree of disability in performing activities of daily living: ≤2: functional independent; 3-5: various degrees of functionally dependence; 6: deceased. Primary complications were defined as new or worsened stroke, intracranial hemorrhage (ICH) and death.
SAS version 9.4 (Cary, NC, USA) was used for statistical analyses. For categorical variables, chi-square and Fisher’s exact test were used to determine p-value. T-test was used for normal data and Wilcoxon test for skewed data. Bivariate analyses were performed for association with the outcomes and logistic regression for odds ratio.
From January 2013 through April of 2017, 551 patients underwent carotid interventions. Of these, 120 patients (21.7%) underwent urgent carotid interventions to treat acute neurologic symptoms, including cerebral TIA, (n=20, 16.7%) and ischemic stroke (n=100, 83.3%). For these acute neurologic events, urgent carotid interventions performed included CEA (n=96), CAS (n=22), one CEA with a middle cerebral artery aspiration thrombectomy for an acute carotid / intracranial occlusion and one carotid embolectomy. The average age was 68.3 years (range: 38– 91) and 82 patients were male (68.3%). The most common comorbidity was hypertension (n=116, 97%), followed by hyperlipidemia (n=112, 93%), history of smoking (n=84, 70%), diabetes (n=41,34%), coronary artery disease with a history of myocardial infarction (n=34, 28%), and stage III or greater CKD (n=31, 26%). The overall 30-day stroke and death rate for this cohort was 10.8% (13/120).
There were a total of 13 primary complications (Table I). Seven of these patients underwent CEA, 6 patients underwent CAS alone or CAS with intracranial thrombectomy. Nearly a third (4/13) of all the stroke/death complications occurred following procedures done within 24 hours (day 0). An additional 46% of the complications (6/13) occurred following procedures performed within 48 hours (days 1 – 2). Three of the complications occurred after day 2 of hospitalization (23%,3/13). Of all the patients with complications, 11 (85%,n=11/13) had perioperative strokes: 6 (46%, n=6/13) patients had ICH, 4 (30%, n=6/13) patients had perioperative strokes, and one patient had contralateral ICH. There were three deaths (23%, n=3/13).
Bivariate analysis of the entire cohort (n=120) and 10 different patient variables, including comorbidities and presenting stroke severity scores (NIHSS and ASPECTS), demonstrated a correlation between admission NIHSS and discharge mRS score. To define this association, we asked whether patients with a presenting minor or moderate stroke (NIHSS ≤ 10) were more likely to achieve functional independence at discharge (mRS ≤ 2) compared to patients presenting with larger strokes (NIHSS > 10). The cohort was divided into patients with an admit NIHSS ≤ 10 (n=100) and >10 (n=20), and this delineation between NIHSS ≤ 10 and >10 proved significant on bivariate analysis for mRS score (p=0.0029). Logistic regression was performed to compare admission NIHSS ≤10 and discharge mRS of ≤2 or ≥3. This analysis demonstrates that patients presenting with large strokes, NIHSS >10, are nearly four times more likely to have functional dependence at discharge than patients presenting with minor to moderate strokes, NIHSS of ≤10 (Table II). This underscores the safety of urgent carotid interventions in patients with minor and moderate-sized strokes, especially when compared to patients with larger, more severe strokes.
Bivariate analysis also demonstrated a correlation between timing of intervention and discharge mRS. Time from presentation to CEA/CAS, quantified as days to procedure ≤2 (n=56) and >2 (n=64) were compared with discharge mRS and found to be associated on bivariate analysis (p=0.0007). Logistic regression revealed that patients undergoing CEA/CAS at ≤2 days following presentation were 3.4 times more likely than patients undergoing CEA/CAS >2 days after presentation to be discharged with decreased functional dependence, or an mRS ≥3. (95% CI 1.4-8.7, Table II). These results highlight the safety of waiting more than 48 hours before urgent carotid intervention in patients with a single TIA or stroke.
In order to create a more homogenous population for analysis, we then omitted emergent carotid interventions, which included any intervention done on day 0 (within 24 hours) for unstable neurological symptoms, such as crescendo TIAs and stroke-in-evolution. Removing these unstable neurological patients from the cohort left two groups for analysis: patients undergoing intervention 1-2 days following presentation (n=43) and those undergoing intervention >2 days after presentation (n=64). Within this subset, bivariate analysis showed discharge mRS to correlate with time to procedure (days 1 – 2 compared to >2 days (p=0.012). Logistic regression analysis demonstrated
the odds of having a discharge mRS ≥3 are 3.4 times more likely for patients with procedure performed at 1-2 days compared to >2 days (3.4; 95%CI 1.3-9.1), again stressing the importance of waiting > 48 hours after a TIA or stroke. Admit NIHSS in this cohort that excluded unstable neurological symptoms also demonstrated that patients with an admission NIHSS >10 are 5.7 times more likely to have a discharge mRS ≥3, compared to patients with an admit NIHSS ≤10 (Table II).
There is increasing evidence that pre-procedure ASPECTS predicts functional dependence on discharge following intracranial thrombecotmy, with a score > 7 associated with better outcome2. We asked whether ASPECTS can similarly be predictive of outcomes of urgent extracranial carotid intervetions. In order to do this, we calculated the ASPECTS for all available admission head CT (n=108/120). Of the ASPECTS calculated, 14 patients (12.9%) had ASPECTS of ≤ 7, 94 patients (87.0%) had ASPECTS of 8-10. However, bivariate analysis based on discharge mRS score and primary complication was not significantly associated with ASPECTS (p=0.76 and p=0.65, respectively). Our data demonstrates that ASPECTS is not an adequate predictor of outcome in urgent extracranial carotid interventions.
Growing bodies of evidence suggests the safety of urgent carotid interventions in select patients1,3 However, the presenting patient characteristics that predict low complication rates and functional independence in this high-risk subset of patients are not well-defined. We demonstrates that urgent carotid interventions can be safely performed in select patients with minor to moderate strokes (NIHSS < 10) after 48 hours, resulting in functional independence as assessed by use of the mRS score on discharge. Carotid interventions done within 48 hours are associated with significantly increased risks. Improved safety of delaying urgent carotid interventions for 48 hours within stroke presentation has previously been demonstrated in a large Swedish Vascular registry study4. However, to our knowledge, this is the first time that neurological functional outcomes have been correlated to presenting stroke severity and time to intervention for acute CEA and CAS. By demonstrating a clear correlation between admission NIHSS and interval time to procedure with independent functional outcomes, we aim to clarify clinical decision-making for patients presenting with acutely symptomatic carotid lesions.
Loftus IM, Paraskevas KI, Naylor AR. Urgent Carotid Endarterectomy Does Not Increase Risk and Will Prevent More Strokes. Angiology. 2017;68(6):469-471.
Hill MD, Demchuk AM, Goyal M, et al. Alberta Stroke Program early computed tomography score to select patients for endovascular treatment: Interventional Management of Stroke (IMS)-III Trial. Stroke. 2014;45(2):444-449.
Rantner B, Schmidauer C, Knoflach M, Fraedrich G. Very urgent carotid endarterectomy does not increase the procedural risk. Eur J Vasc Endovasc Surg. 2015;49(2):129-136.
Stromberg S, Gelin J, Osterberg T, et al. Very urgent carotid endarterectomy confers increased procedural risk. Stroke. 2012;43(5):1331-1335.

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