Heck, Donald

Importance Cerebral hemodynamic impairment in patients with asymptomatic internal carotid artery (ICA) stenosis is associated with reduced cognition. It is uncertain whether revascularization might be an effective treatment for cognitive impairment in these patients. Objective To test whether any cognitive benefit from revascularization of high-grade, asymptomatic ICA stenosis varies based on the degree of baseline cerebral hemodynamic impairment. Design, Setting, and Participants This substudy was conducted within a multicenter phase 3 randomized clinical trial. Adults (aged 35-86 years) without dementia with eighth-grade education or higher and unilateral asymptomatic ICA stenosis greater than or equal to 70% were enrolled from January 2018 to July 2024 at 61 sites in North America (last follow-up in July 2025). Of 607 participants screened from 2485 in CREST-2, 392 were enrolled. Magnetic resonance or computed tomographic perfusion imaging tested for baseline hemodynamic impairment defined by delayed time-to-peak (TTP) arrival of intravenous contrast in the hemisphere ipsilateral minus contralateral to the stenotic artery. Intervention Carotid revascularization (endarterectomy or stenting) plus intensive medical management (IMM) vs IMM alone. Main Outcomes and Measures The primary outcome was the difference in composite cognitive z score over 1 year based on 5 cognitive tests. The primary analysis tested for an interaction between treatment group (revascularization vs IMM alone) and degree of baseline hemodynamic impairment among those with reduced baseline cognition (cognitive z score ≤−1.0 SD). Results Of 392 participants enrolled (mean age, 71 years; 125 [32%] females), 61 were excluded for missing baseline imaging and 40 for missing cognitive examinations or other covariates, leaving 291 with complete data. Fifty-one had reduced cognition at baseline (25 in the revascularization group and 26 in the IMM alone group). TTP ranged from no interhemispheric TTP delay to a more-than-2-second delay. Mean (SD) cognitive z scores were −1.36 (0.51) at baseline and −1.17 (0.47) at 1 year in the revascularization group and −1.34 (0.83) at baseline and −1.01 (0.97) at 1 year in the IMM alone group. The primary analysis showed no difference in cognition by treatment group over 1 year, adjusting for treatment group × hemodynamic status interaction and other covariates (adjusted difference in cognitive z score, −0.15 SD [95% CI, −0.54 to 0.24]). The interaction was not significant (β estimate = 0.018 [95% CI, −0.025 to 0.061]; P = .40). Conclusions and Relevance In this substudy of a randomized clinical trial, there was no differential effect of revascularization vs IMM alone on cognition over 1 year by cerebral hemodynamic status among those with baseline reduced cognition, suggesting that revascularization does not improve cognitive dysfunction by restoring flow to the brain in chronic asymptomatic carotid stenosis. Trial Registration ClinicalTrials.gov Identifier: NCT03121209

Introduction: Increasing stenosis has been questioned as a factor increasing risk of carotid endarterectomy (CEA) or carotid stenting (CAS) in patients with severe asymptomatic carotid stenosis. Hypothesis: Greater severity of carotid stenosis is associated with higher rates of periprocedural stroke and death following revascularization for asymptomatic patients. Methods: Asymptomatic patients with carotid stenosis ≥ 70% by ultrasound or ≥ 60% by angiogram were eligible for the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST). Patients who had a catheter-angiogram were divided into tertiles based on the degree of stenosis. Outcomes were the occurrence of any stroke or death at 30 days. Proportional hazards models adjusting for age and treatment were used to assess risk of 30 day stroke or death by tertile of stenosis. Results: Among 1181 asymptomatic patients, qualifying angiograms were done for 662 patients who had assigned procedure performed within 30 days of randomization. Median % stenosis was 62.6, 73.4, and 83.0 for the tertiles that otherwise differed only for female sex (40% female in tertile 1, 36% in tertile 2, 29% in tertile 3, p=0.01). The 30-day stroke and death rates did not differ significantly by severity of stenosis (Table), but the number of stroke and deaths was only 14 across the tertiles (Table). Similarly meaningful comparison of CEA vs CAS was not possible. Conclusion: This is the largest contemporary study of carotid angiograms performed in patients with severe asymptomatic carotid stenosis. No relationship was detected between severity of stenosis and 30-day stroke and death. The safety of CEA and CAS in asymptomatic patients limits detection of other factors that may increase risk because so few events complicate these procedures.

Background An increased risk of periprocedural stroke and death has been reported for older patients treated with carotid stenting (CAS). Selection of patients for CAS could be improved if patient or artery characteristics responsible for this higher risk could be identified. Methods The 1123 CREST patients randomized to CAS who received CAS within 30-days were analyzed. From the CREST sites, risk factors for atherosclerosis (hypertension, diabetes, and dyslipidemia) and arterial characteristics by angiography (lesion length, eccentric lesions, ulcerated lesions, and percent stenosis) were assessed. From the CREST core labs, potential mediators of the age effect included peak systolic velocity (ultrasound core, available on 853 patients) and arterial characteristics (angiographic core, available on 1042 patients, narrow/no ulcer or wide mouth, lesion location, and distal tortuosity). Mediation analysis assessed impact of adjustment for these factors on the magnitude of the estimated increased risk for CAS at older ages. Results After adjustment for sex and symptomatic status, there was a 1.72-times (95% CI: 1.26 - 2.37) increased risk of periprocedural stroke and death associated with each decade of patient age. Adjustment for lesion length as assessed in the clinical center significantly attenuated this increased risk at older ages to 1.66 (95% CI: 1.20 - 2.29, p = 0.039), an 8.3% attenuation. No other factor showed evidence as a contributor to the periprocedural increased risk of stroke and death in older patients (p > 0.10). Conclusion These data suggest that a longer carotid artery lesion length is a significant contributor to the increased risk of CAS in the elderly. However, attenuation of the age effect was modest, less than a 10% change in the hazard ratios. Other potential mediators such as tortuosity and atherosclerosis of the aortic arch and great vessels were not assessed. Non-anatomic factors that are more common with advancing age such as cerebral white matter disease and subclinical dementia were also not assessed and may play a role in how elderly patients respond to ischemic insults.

Purpose: Various imaging approaches are utilized for evaluating acute stroke patients. Despite numerous studies, there is no clear evidence that one approach is superior to another for identifying which patients will benefit from mechanical thrombectomy (MT). The PICS registry was established to determine the imaging modalities being employed to triage acute stroke patients for MT and to assess their impact on patient functional outcome. Methods: Patients were enrolled across 35 centers. For each patient, the baseline imaging modality was recorded to determine the utilization rates of noncontrast CT (NCCT), CT perfusion (CT-P), and MRI diffusion weighted imaging (DWI). All patients subsequently treated by the Penumbra System per standard of care were followed for 3 months after the procedure to assess functional outcome using the modified Rankin Scale (mRS). Results: A total of 305 patients were enrolled in this registry, of which 267 had the requisite imaging modalities used for this analysis. Of these, 49.4% were females. Mean age was 66.6 ± 15.9 years; median NIHSS score was 17.0 (IQR 12-21). The median time from stroke onset to presentation was 2.3 hours, from stroke symptom onset to arterial puncture was 4.8 hours, and from arterial puncture to end of thromboaspiration was 73.0 minutes. Post-treatment evaluation revealed that 83.5% of patients were successfully recanalized to TIMI 2/3 (from TIMI 0/1) with 43.5% achieving a 90-day mRS of 0-2. All cause mortality was 19.9% with symptomatic intracranial hemorrhage reported in 4.5% of the patients. The principal imaging modalities used for patient triage were NCCT in 61.8%, CT-P in 27.3% and DWI in 10.9% of the study population. Of the patients selected for NCCT, 42.5% were functionally independent at 90 days, whereas for CT-P and DWI, the rates were 45.9% and 42.9%, respectively. There was no significant difference between groups for patient age, baseline NIHSS, time from onset to presentation, time from arterial puncture to end of thromboaspiration. The time from stroke symptom onset to groin puncture was significantly different in the DWI cohort (p<0.0001) with a median of 4.4 hrs for NCCT, 4.8 hrs for CTP, and 6.5 hrs for DWI. There was a significant difference in % of female patients with CTP 37.0%, DWI 48.3%, and NCCT 55.2% (p=0.034). Conclusion: The type of imaging modality utilized to triage acute ischemic stroke patients for MT varies widely across the US. Based on the present findings, the imaging approach appears to have little impact on patient functional outcome after MT.

Abstract Background The multicenter prospective CREST‐2 Registry (C2R) provides recent experience in performing carotid artery stenting (CAS) for interventionists to ensure safe performance of CAS. Objective To determine the periprocedural safety of CAS performed using a transradial approach relative to CAS performed using a transfemoral approach. Methods Patients with ≥70% asymptomatic and ≥50% symptomatic carotid stenosis, ≤80 years of age and at standard or high risk for carotid endarterectomy (CEA) are eligible for the C2R. The primary endpoint was a composite of severe access‐related complications. Comparisons were made using propensity‐score matched logistic regression. Results The mean age of the cohort was 67.6 ± 8.2 years and 1906 (35.1%) were female. Indications for CAS included 4063 (74.9%) for primary atherosclerosis. A total of 2868 (52.8%) cases underwent CAS for asymptomatic disease. Transradial access was used in 213 (3.9%) patients. The transradial cohort had lower use of general anesthesia (1.5% vs. 6.3%, p = 0.007) and higher use of distal embolic protection (96.7% vs. 89.4%, p = 0.0004). There were no significant differences between radial and femoral access groups in terms of a composite of major access‐related complications (0% vs. 1.1%) or a composite of periprocedural stroke or death (3.3% vs. 2.4%; OR = 1.4 [confidence intervals 0.6, 3.1]; p = 0.42). Conclusion We found no significant differences in rates of major access‐related complications or periprocedural stroke or death with CAS performed using transradial compared to transfemoral access. Our results support incorporation of the transradial approach to clinical trials comparing CAS to other revascularization techniques.