Nonstenotic Carotid Disease Research Articles

Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial.

Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke. Data are from ESCAPE-NA1, arandomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease. After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke. Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove acausal relationship.

P.067 The decision to revascularize in symptomatic non-stenotic carotid disease: results from the Hot Carotid Qualitative study

Background: Little evidence exists to guide the management of symptomatic non-stenotic carotid disease (SyNC). SyNC, which refers to carotid lesions with less than 50% artery stenosis, has been increasingly implicated as a cause of stroke and TIA. Methods: Semi-structured interviews with 22 stroke physicians from 16 centers were conducted as part of the Hot Carotid Qualitative Study. This study explored decision-making approaches, opinions and attitudes regarding the management of symptomatic carotid disease. Presented here are a subset of results related to the decision to revascularize patients with SyNC. Results: Thematic analysis revealed equipoise in the decision to revascularize patients with SyNC. Participants discussed a desire to use imaging features (e.g plaque rupture and plaque morphology) to inform the decision to revascularize, though significant uncertainty remains in appraising the risk conferred by certain features. Experts support further study to better understand the use of these features in risk appraisal for patients with SyNC. Conclusions: The decision to revascularize patients with SyNC is an area with significant equipoise. Experts identify the use of imaging features as an important tool in informing the decision to pursue revascularization in patients with SyNC though more study is required in this area to better inform practice.

Nonstenotic Carotid Plaques and Embolic Stroke of Undetermined Source: A Multimodality Review.

Symptomatic nonstenotic carotid artery disease has been increasingly recognized as a thromboembolic source in patients who would otherwise be classified as having embolic stroke of undetermined source. Evidence suggests that certain plaque features seen on sonography, CT, and MR imaging in nonstenotic carotid artery disease may predispose to recurrent stroke in patients with embolic stroke of undetermined source. We performed a focused literature review to further study plaque features in the context of embolic stroke of undetermined source and to determine which plaque features may be associated with ipsilateral ischemic events in such patients. Plaque thickness as seen on both ultrasound and CT appears to have a consistent association with ipsilateral stroke in patients with embolic stroke of undetermined source across multiple studies. Intraplaque hemorrhage as seen on MR imaging is now understood to have a strong association with ipsilateral stroke in patients with embolic stroke of undetermined source. Continued study of various plaque features as seen on different modalities is warranted to uncover other potential associations.

Prevalence of Symptomatic Nonstenotic Carotid Disease Using Simultaneous Non-Contrast Angiography and Intraplaque Hemorrhage Imaging for MR Screen Protocol.

Background: To determine the prevalence of symptomatic nonstenotic carotid disease (SyNC) using simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging for patients with acute stroke as an MR screen protocol and to assess imaging findings of carotid plaques. Patients and Methods: From May 2020 to October 2021, 2459 patients with suspected acute neurological symptoms were evaluated with brain diffusion-weighted imaging (DWI) and carotid SNAP imaging. We analyzed the degree of stenosis and intraplaque hemorrhage (IPH) using SNAP imaging. Prevalence of SyNC and risk factors for stroke in patients with SyNC were determined. We performed subgroup multivariate analysis between SyNC and other etiologies of stroke (non-SyNC). Results: Of 4608 carotid arteries in 2304 patients enrolled in this study, 454 (9.9%) plaques (both lesions in 128 patients) were found on SNAP imaging. Of these plaques, 353 (77.8%) showed stenosis of <50%. Of plaques with <50% stenosis, 47 (13.3%) patients had a territorial acute focal infarction. Seventeen (36.2%) were classified with embolic stroke of undetermined source (ESUS) and SyNC. High maximal wall thickness and carotid IPH were identified as influencing factors for SyNC. Conclusion: For patients with <50% stenosis and territorial infarction, SyNC is a relatively important source of stroke. Especially, high maximal wall thickness and carotid IPH are important risk factors for SyNC.

Symptomatic nonstenotic carotid disease: Evaluation of a proposed classification scheme in a prospective cohort

IntroductionUnraveling symptomatic nonstenotic carotid disease (SyNC) as a stroke etiology from other cryptogenic stroke may have important implications for defining natural history and for tailoring secondary prevention strategies. We aim to describe the characteristics of the plaques in a prospectively-collected cohort of patients with non-invasive imaging suggesting symptomatic carotid stenosis but whose DSA demonstrated nonstenotic atheromatous disease, and to evaluate the recurrence rate depending on the type of SyNC. MethodsWe reviewed prospectively-collected data for patients presenting with new neurologic events and non-invasive imaging suggestive of moderate or severe (≥50%) carotid stenosis between July 2016 and October 2018. Patients were included in the present study if the degree of stenosis on DSA was < 50%. We assigned these patients into groups based on a previously-proposed working definition of SyNC, and analyzed the rate of recurrent stroke in the following 6 months. Results28 patients had DSA-confirmed < 50% stenosis and constituted the study cohort. The median age was 73 years and 64% were male; median presenting NIHSS was 1 (IQR 0–3). The great majority (86%) of carotid plaques had high-risk features including ulcerated plaque (n = 21, 75%) and plaque > 3 mm thick (n = 18, 64%). 17 of 28 patients (61%) met classification criteria for “definite” or “probable” SyNC. Three of five patients in the “definite SyNC” group experienced recurrent neurologic events. ConclusionThe majority of patients with non-invasive imaging suggesting carotid stenosis harbor symptomatic carotid disease per current classifications despite DSA stenosis < 50%. Current classification schema may allow for risk stratification of SyNC patients and these findings warrant further study.

Meta-Analysis Comparing the Frequency of Carotid Artery Stenosis in Patients With Atrial Fibrillation and Vice Versa

Atrial fibrillation (AF) and carotid stenosis (CS) can coexist and this association has been reported to result in a higher risk of stroke than attributed to either condition alone. Here we aimed to summarize the data on the association of CS and AF. MEDLINE and Embase were searched to identify all published studies providing relevant data through February 27, 2020. Random-effects meta-analysis method was used to pool estimates of prevalence. Heterogeneity was assessed by mean I-squared statistic. Forty-eight studies were included, 20 reporting on the prevalence of carotid disease in a pooled population of 49,070 AF patients, and 28 on the prevalence of AF in a total of 2,288,265 patients with carotid disease. The pooled prevalence of CS in AF patients was 12.4% (95% confidence interval [CI] 8.7 to 16.0, I2 93%; n = 3,919), ranging from 4.4% to 24.3%. The pooled prevalence of carotid plaque was 48.4% (95% CI 35.2 to 61.7, I2 = 99%; n = 4292). The prevalence of AF in patients with CS was 9.3% (95% CI 8.7 to 10.0, I2 99%; n = 2,286,518), ranging from 3.6% to 10.0%. This prevalence was much higher (p <0.001) in patients undergoing carotid artery stenting (12.7%, 95% CI 11.3 to 14.02, I2 38.3%) compared with those undergoing carotid endarterectomy (6.9%, 95% CI 8.3 to 10.4, I2 94.1%). There was no difference in AF prevalence between patients with CS, with and without previous cerebrovascular event (p >0.05). In conclusion, AF and CS frequently coexist, with about one in ten patients with AF having CS, and vice versa. In addition, nonstenotic carotid disease is present in about half of AF patients. These findings have important implications for AF screening in patients with CS, stroke prevention, and the opportunities to intervene on common risk factors.

Letter by Kadian-Dodov and Olin Regarding Article, “Embolic Stroke of Undetermined Source and Symptomatic Nonstenotic Carotid Disease”

Letter by Kadian-Dodov and Olin Regarding Article, “Embolic Stroke of Undetermined Source and Symptomatic Nonstenotic Carotid Disease”

Response by Ospel and Goyal to Letter Regarding Article, “Embolic Stroke of Undetermined Source and Symptomatic Nonstenotic Carotid Disease”

Response by Ospel and Goyal to Letter Regarding Article, “Embolic Stroke of Undetermined Source and Symptomatic Nonstenotic Carotid Disease”

Ipsilateral Nonstenotic Carotid Disease in Minor Ischemic Stroke: an Exploratory Analysis of The POINT Randomized Clinical Trial

Background and aimIpsilateral nonstenotic carotid disease is increasingly recognized as an etiology of ischemic stroke, however tailored treatment strategies are lacking. We aimed to examine clinical characteristics and treatment effects in patients with minor ischemic stroke associated with ipsilateral nonstenotic carotid disease in the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. MethodsWe performed an exploratory analysis of the interaction of the treatment effects of aspirin plus clopidogrel versus aspirin monotherapy, stratified by presence of ipsilateral nonstenotic carotid disease in patients with minor ischemic stroke in the POINT trial. ResultsFor this exploratory analysis, 167 patients presenting with ischemic stroke and ipsilateral nonstenotic carotid disease, defined as 1%-49% carotid stenosis ipsilateral to the corresponding territory of ischemic stroke, and 833 patients no carotid disease were included. Compared to patients with no carotid disease, patients with ipsilateral nonstenotic carotid disease were older (68.5 ± 11.3 years versus 61.3 ± 12.8 years; P < 0.001), and had a higher prevalence of hypertension (76.6% versus 59.2%, P < 0.001), ischemic heart disease (13.8% versus 5.4%, P < 0.001), and tobacco use (past: 34.1% versus 25.2%, P = 0.005; present: 27.5% versus 22.8%, P = 0.005). 5.4% of patients with ipsilateral nonstenotic carotid disease had recurrent ischemic stroke within 14 days. Patients receiving dual antiplatelet therapy had a numerical reduction in recurrent ischemic stroke compared to patients receiving aspirin monotherapy, however the exploratory analysis was underpowered to detect a statistically significant difference in treatment effect (HR 0.50, 95% CI 0.18-1.40, P = 0.19). ConclusionPatients with minor ischemic stroke and ipsilateral nonstenotic carotid disease had a high risk of early stroke recurrence in the POINT trial. Dual antiplatelet therapy provided a non-statistically significant reduction in recurrent ischemic stroke with no difference in safety outcomes compared to aspirin monotherapy. Further study is needed to determine if early and short duration dual antiplatelet therapy is beneficial for all patients with ipsilateral nonstenotic carotid disease.

Embolic Stroke of Undetermined Source and Symptomatic Nonstenotic Carotid Disease.

Embolic Stroke of Undetermined Source and Symptomatic Nonstenotic Carotid Disease.

Quantitative Assessment of Carotid Atherosclerosis in a Healthy Population

To evaluate the prevalence and extent of carotid atherosclerosis in a general healthy population, duplex ultrasound imaging was performed in 909 men and women aged 40-79 years as part of the prospective Bruneck Ischemic Heart Disease and Stroke Prevention Study. Atherosclerotic lesions were found in 47.8% of men and 36.3% of women. Sex differences in the prevalence rates were most pronounced from age 40 to 60 years with a convergence occurring in the 7th decade. The age range of 60-69 years was found to be the crucial period for the development of advanced carotid artery disease. The frequency of internal carotid artery stenosis (> 50%) in elderly men and women (60-79 years) was 10.5 and 5.5%. In nonstenotic carotid artery disease the lumen diameter turned out to be a useful indirect measure of the vascular status.