Long-Term Stroke Risk in Patients With New Ischemic Brain Lesions on MRI After Carotid Revascularization

BACKGROUND: Carotid artery revascularization can result in new ischemic brain lesions on diffusion-weighted magnetic resonance imaging. This study aimed to investigate the relationship between periprocedural ischemic diffusion-weighted imaging (DWI) lesions after carotid artery revascularization and recurrent long-term cerebrovascular events. METHODS: A secondary observational prospective cohort analysis of existing clinical trial data was performed on 162 patients with symptomatic carotid stenosis that were previously randomized to carotid artery stenting or carotid endarterectomy in the ICSS (International Carotid Stenting Study) and included in the magnetic resonance imaging substudy. Magnetic resonance imagings were performed 1 to 7 days before and 1 to 3 days after treatment. The primary composite clinical outcome was the time to any stroke or transient ischemic attack during follow-up. Patients with new diffusion-weighted imaging (DWI) lesions on posttreatment magnetic resonance imaging scan (DWI+) were compared with patients without new lesions (DWI-). RESULTS: The median time of follow-up was 8.6 years (interquartile range, 5.0-12.5). Kaplan-Meier cumulative incidence for the primary outcome after 12.5-year follow-up was 35.3% (SE, 8.9%) in DWI+ patients and 31.1% (SE, 5.6%) in DWI- patients. Uni- and multivariable regression analyses did not show significant differences (hazard ratio, 1.50 [95% CI, 0.76-2.94] and hazard ratio, 1.30 [95% CI, 0.10-1.02], respectively). Higher event rate of the primary outcome in DWI+ patients in the overall cohort was mainly caused by events in the carotid artery stenting group. CONCLUSIONS: Based on our outcome analysis within the ICSS magnetic resonance imaging substudy, DWI lesions following carotid revascularization did not seem to have a relationship with long-term stroke risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ISRCTN 25337470.</p

Long-Term Stroke Risk in Patients With New Ischemic Brain Lesions on MRI After Carotid Revascularization

BACKGROUND: Carotid artery revascularization can result in new ischemic brain lesions on diffusion-weighted magnetic resonance imaging. This study aimed to investigate the relationship between periprocedural ischemic diffusion-weighted imaging (DWI) lesions after carotid artery revascularization and recurrent long-term cerebrovascular events. METHODS: A secondary observational prospective cohort analysis of existing clinical trial data was performed on 162 patients with symptomatic carotid stenosis that were previously randomized to carotid artery stenting or carotid endarterectomy in the ICSS (International Carotid Stenting Study) and included in the magnetic resonance imaging substudy. Magnetic resonance imagings were performed 1 to 7 days before and 1 to 3 days after treatment. The primary composite clinical outcome was the time to any stroke or transient ischemic attack during follow-up. Patients with new diffusion-weighted imaging (DWI) lesions on posttreatment magnetic resonance imaging scan (DWI+) were compared with patients without new lesions (DWI-). RESULTS: The median time of follow-up was 8.6 years (interquartile range, 5.0-12.5). Kaplan-Meier cumulative incidence for the primary outcome after 12.5-year follow-up was 35.3% (SE, 8.9%) in DWI+ patients and 31.1% (SE, 5.6%) in DWI- patients. Uni- and multivariable regression analyses did not show significant differences (hazard ratio, 1.50 [95% CI, 0.76-2.94] and hazard ratio, 1.30 [95% CI, 0.10-1.02], respectively). Higher event rate of the primary outcome in DWI+ patients in the overall cohort was mainly caused by events in the carotid artery stenting group. CONCLUSIONS: Based on our outcome analysis within the ICSS magnetic resonance imaging substudy, DWI lesions following carotid revascularization did not seem to have a relationship with long-term stroke risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ISRCTN 25337470

Editor's Choice - Predictors of New Ischaemic Brain Lesions on Diffusion Weighted Imaging After Carotid Stenting and Endarterectomy: A Systematic Review

OBJECTIVES: Peri-procedural ischaemic brain lesions on diffusion weighted imaging (DWI) after carotid endarterectomy (CEA) and carotid artery stenting (CAS) have been related to a higher chance of recurrent cerebrovascular events. This systematic review provides an overview of patient characteristics associated with increased risk of new DWI lesions. METHODS: MEDLINE, EMBASE, and Cochrane library databases were systematically searched (update November 2018) for studies reporting post-procedural DWI lesions after CEA or CAS. Data derived from both procedures were analysed separately. Studies reporting predictive features that were present prior to intervention were assigned to 10 categories: age, gender, cardiovascular risk factors, symptomatology, plaque vulnerability, atherosclerotic burden, cerebrovascular haemodynamics, carotid/arch anatomy, inflammatory markers, and markers of coagulation. A semi-quantitative analysis was performed by plotting studies that found an association between the investigated features and DWI lesions against those that did not find an association. RESULTS: Forty-six studies (5018 patients) were included: 10 reported only CEA, 33 CAS, and three both interventions. 68.0% of 1873 CEA patients and 55.9% of 3145 CAS patients were symptomatic. The weighted prevalence of DWI lesions was 18.1% (95% CI 14.0-22.7%) in CEA patients compared with 40.5% (95% CI 35.4-45.7%) in CAS patients. Studies reporting on CEA patients predominantly found an increased risk in symptomatic patients (two of seven studies, including 848/1661 patients), those with impaired haemodynamics (five of five studies), and increased inflammatory markers (two of three studies). Studies reporting on CAS patients often found a positive association with age (10/26 studies), high plaque vulnerability (25/34 studies), or complex carotid/arch anatomy (three out of five studies). CONCLUSIONS: For patients undergoing CEA, symptomatic status, impeded cerebral haemodynamics, and increased inflammatory markers are associated with increased susceptibility to peri-operative DWI lesions. In CAS patients, higher age, plaque vulnerability and complex carotid/aortic arch anatomy were identified as risk factors. These clinical predictors may assist with decision making on patient selection for medical treatment, CEA or CAS

Magnetic Resonance Imaging Identified Brain Ischaemia in Symptomatic Patients Undergoing Carotid Endarterectomy Is Related to Histologically Apparent Intraplaque Haemorrhage

Objective: Intraplaque haemorrhage (IPH) has been independently associated with a higher risk of future ipsilateral stroke in patients with carotid artery stenosis. Evaluation of plaque characteristics may contribute to risk assessment of recurrent (silent) cerebrovascular events in order to prioritise patients for timing of treatment. It is unknown if patients showing histologically apparent IPH also have increased risk of silent ischaemic brain lesions in the waiting period between index event and revascularisation. Methods: A retrospective analysis was performed based on prospectively collected data of patients included simultaneously in the magnetic resonance imaging (MRI) substudy of the International Carotid Stenting Study and Athero-Express biobank. Patients randomised for carotid endarterectomy (CEA) underwent surgery between 2003 and 2008. Brain MRI was performed one to seven days prior to CEA. Plaques were histologically examined for presence of IPH. The primary outcome parameter was presence of silent ipsilateral brain ischaemia on magnetic resonance diffusion weighted imaging (MR-DWI) appearing hypo or isointense on apparent diffusion coefficient. Results: Fifty-three patients with symptomatic carotid stenosis meeting the study criteria were identified, of which 13 showed one or more recent ipsilateral DWI lesion on pre-operative scan. The median time between latest ipsilateral neurological event and revascularisation was 45 days (range 6–200) in DWI negative patients vs. 34 days (range 6–74, p = .16) in DWI positive patients. IPH was present in 24/40 (60.0%) DWI negative patients vs. 12/13 (92.3%) DWI positive patients (OR 8.00; 95% CI 0.95–67.7, p = .06). Multivariable logistic regression analysis correcting for age and type of index event revealed that IPH was independently associated with DWI lesions in the waiting period till surgery (OR 10.8; 95% CI 1.17–99.9, p = .04). Conclusion: Symptomatic patients with ipsilateral carotid stenosis and silent brain ischaemia on pre-operative MR-DWI, more often showed pathological evidence of IPH compared with those without ischaemic lesions. This identifies carotid IPH as a marker for patients at risk of silent brain ischaemia and possibly for future stroke and other arterial disease complications. Such patients may be more likely to benefit from CEA than those without evidence of ipsilateral carotid IPH

Intra-Operative Hypotension is a Risk Factor for Post-operative Silent Brain Ischaemia in Patients With Pre-operative Hypertension Undergoing Carotid Endarterectomy

Objective: Intra-operative haemodynamic instability during carotid endarterectomy (CEA) has been associated with an increased risk of procedural stroke. Diffusion weighted imaging (DWI) lesions have been proposed as a surrogate marker for peri-operative silent cerebral ischaemia. This study aimed to investigate the relationship between peri-operative blood pressure (BP) and presence of post-operative DWI lesions in patients undergoing CEA. Methods: A retrospective analysis was performed based on patients with symptomatic CEA included in the MRI substudy of the International Carotid Stenting Study. Relative intra-operative hypotension was defined as a decrease of intra-operative systolic BP ≥ 20% compared with pre-operative (‘baseline’) BP, absolute hypotension was defined as a drop in systolic BP < 80 mmHg. The primary endpoint was the presence of any new DWI lesions on post-operative MRI (DWI positive). The occurrence and duration of intra-operative hypotension was compared between DWI positive and DWI negative patients as was the magnitude of the difference between pre- and intra-operative BP. Results: Fifty-five patients with symptomatic CEA were included, of whom eight were DWI positive. DWI positive patients had a significantly higher baseline systolic (186 ± 31 vs. 158 ± 27 mmHg, p = .011) and diastolic BP (95 ± 15 vs. 84 ± 13 mmHg, p = .046) compared with DWI negative patients. Other pre-operative characteristics did not differ. Relative intra-operative hypotension compared with baseline occurred in 53/55 patients (median duration 34 min; range 0–174). Duration of hypotension did not differ significantly between the groups (p = .088). Mean systolic intra-operative BP compared with baseline revealed a larger drop in BP (−37 ± 29 mmHg) in DWI positive compared with DWI negative patients (−14 ± 26 mmHg, p = .024). Absolute intra-operative systolic BP values did not differ between the groups. Conclusion: In this exploratory study, high pre-operative BP and a larger drop of intra-operative BP were associated with peri-procedural cerebral ischaemia as documented with DWI. These results call for confirmation in an adequately sized prospective study, as they suggest important consequences for peri-operative haemodynamic management in carotid revascularisation

Cerebral Small Vessel Disease in Standard Pre-operative Imaging Reports Is Independently Associated with Increased Risk of Cardiovascular Death Following Carotid Endarterectomy

OBJECTIVE: Cerebral white matter lesions (WMLs) and lacunar infarcts are surrogates of cerebral small vessel disease (SVD). WML severity as determined by trained radiologists predicts post-operative stroke or death in patients undergoing carotid endarterectomy (CEA). It is unknown whether routine pre-operative brain imaging reports as part of standard clinical practice also predict short and long term risk of stroke and death after CEA. METHODS: Consecutive patients from the Athero-Express biobank study that underwent CEA for symptomatic high degree stenosis between March 2002 and November 2014 were included. Pre-operative brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) reports were reviewed for reporting of SVD, defined as WMLs or any lacunar infarcts. The primary outcome was defined as any stroke or any cardiovascular death over three year follow up. The secondary outcome was defined as the 30 day peri-operative risk of stroke or cardiovascular death. RESULTS: A total of 1038 patients were included (34% women), of whom 659 (63.5%) had CT images and 379 (36.5%) MRI images available. Of all patients, 697 (67%) had SVD reported by radiologists. Patients with SVD had a higher three year risk of cardiovascular death than those without (6.5% vs. 2.1%, adjusted HR 2.52 [95% CI 1.12-5.67]; p = .026) but no association was observed for the three year risk of stroke (9.0% vs. 6.7%, for patients with SVD vs. those without, adjusted HR 1.24 [95% CI 0.76-2.02]; p = .395). No differences in 30 day peri-operative risk were observed for stroke (4.4% vs. 2.9%, for patients with vs. those without SVD; adjusted HR 1.49 [95% CI 0.73-3.05]; p = .28), and for the combined stroke/cardiovascular death risk (4.4% vs. 3.5%, adjusted HR 1.20 [95% CI 0.61-2.35]; p = .59). CONCLUSION: Presence of SVD in pre-operative brain imaging reports can serve as a predictor for the three year risk of cardiovascular death in symptomatic patients undergoing CEA but does not predict peri-operative or long term risk of stroke