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Background Insight into outcome variation between hospitals could help to improve quality of care. We aimed to assess the validity of early outcomes as quality indicators for acute ischemic stroke care for patients treated with endovascular therapy (EVT). Methods and Results We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a large multicenter prospective cohort study including 3279 patients with acute ischemic stroke undergoing EVT. Random effect linear and proportional odds regression were used to analyze the effect of case mix on between‐hospital differences in 2 early outcomes: the National Institutes of Health Stroke Scale (NIHSS) score at 24 to 48 hours and the expanded thrombolysis in cerebral infarction score. Between‐hospital variation in outcomes was assessed using the variance of random hospital effects (tau 2 ). In addition, we estimated the correlation between hospitals' EVT‐patient volume and (case‐mix–adjusted) outcomes. Both early outcomes and case‐mix characteristics varied significantly across hospitals. Between‐hospital variation in the expanded thrombolysis in cerebral infarction score was not influenced by case‐mix adjustment (tau 2 =0.17 in both models). In contrast, for the NIHSS score at 24 to 48 hours, case‐mix adjustment led to a decrease in variation between hospitals (tau 2 decreases from 0.19 to 0.17). Hospitals' EVT‐patient volume was strongly correlated with higher expanded thrombolysis in cerebral infarction scores ( r =0.48) and weakly with lower NIHSS score at 24 to 48 hours ( r =0.15). Conclusions Between‐hospital variation in NIHSS score at 24 to 48 hours is significantly influenced by case‐mix but not by patient volume. In contrast, between‐hospital variation in expanded thrombolysis in cerebral infarction score is strongly influenced by EVT‐patient volume but not by case‐mix. Both outcomes may be suitable for comparing hospitals on quality of care, provided that adequate adjustment for case‐mix is applied for NIHSS score.

Background Time to reperfusion in patients with ischemic stroke is strongly associated with functional outcome and may differ between hospitals and between patients within hospitals. Improvement in time to reperfusion can be guided by between‐hospital and within‐hospital comparisons and requires insight in specific targets for improvement. We aimed to quantify the variation in door‐to‐reperfusion time between and within Dutch intervention hospitals and to assess the contribution of different time intervals to this variation. Methods and Results We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. The door‐to‐reperfusion time was subdivided into time intervals, separately for direct patients (door‐to‐computed tomography, computed tomography‐to‐computed tomography angiography [CTA], CTA‐to‐groin, and groin‐to‐reperfusion times) and for transferred patients (door‐to‐groin and groin‐to‐reperfusion times). We used linear mixed models to distinguish the variation in door‐to‐reperfusion time between hospitals and between patients. The proportional change in variance was used to estimate the amount of variance explained by each time interval. We included 2855 patients of 17 hospitals providing endovascular treatment. Of these patients, 44% arrived directly at an endovascular treatment hospital. The between‐hospital variation in door‐to‐reperfusion time was 9%, and the within‐hospital variation was 91%. The contribution of case‐mix variables on the variation in door‐to‐reperfusion time was marginal (2%–7%). Of the between‐hospital variation, CTA‐to‐groin time explained 83%, whereas groin‐to‐reperfusion time explained 15%. Within‐hospital variation was mostly explained by CTA‐to‐groin time (33%) and groin‐to‐reperfusion time (42%). Similar results were found for transferred patients. Conclusions Door‐to‐reperfusion time varies between, but even more within, hospitals providing endovascular treatment for ischemic stroke. Quality of stroke care improvements should not only be guided by between‐hospital comparisons, but also aim to reduce variation between patients within a hospital, and should specifically focus on CTA‐to‐groin time and groin‐to‐reperfusion time.

BackgroundRandomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice.MethodsThe Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0–2), and death.ResultsOf 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9–10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, pConclusionsWithout the use of CT perfusion selection criteria, EVT in the 6.5–24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window.

We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58±10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0±10.2 mL/min per 100 mL, mean BPF was 79.2±2.9%, and mean VF was 2.03±0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.

The authors investigated the association of white matter lesions and lacunar infarcts with cognitive performance and whether brain atrophy mediates these associations. Within the Second Manifestations of Arterial Disease-Magnetic Resonance study (2001-2005, the Netherlands), cross-sectional analyses of 522 patients were performed (mean age, 57 years (standard deviation, 10); 76% male). Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid, and white matter lesions. Infarcts were rated visually. Brain volume, ventricular volume, and gray matter volume were divided by intracranial volume to obtain indicators of brain atrophy. Neuropsychological tests assessing executive functioning and memory were performed, and scores were transformed into z scores. The authors used linear regression analyses, adjusted for age, sex, education, intelligence, and vascular risk factors, to investigate the association of white matter lesions and number of lacunar infarcts with cognitive performance. A 1-standard-deviation higher volume of white matter lesions (beta = -0.12, 95% confidence interval: -0.20, -0.04) and the presence of >or=2 lacunar infarcts (beta = -0.48, 95% confidence interval: -0.87, -0.09) were associated with worse executive functioning. These associations remained after adjusting for brain atrophy. Both were not associated with worse memory. Results suggest that subcortical ischemic vascular lesions are associated with decreased executive functioning, but not with memory functioning, independent of brain atrophy.

Objective: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 ± 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid and WML. Total brain volume, ventricular volume and cortical gray matter volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), ventricular fraction (VF) and cortical gray matter fraction (GMF). Location and number of infarcts were rated visually. Results: Mean ± SD BPF was 79.3 ± 2.8%, mean ± SD VF was 2.01 ± 0.95%, and mean ± SD GMF was 36.6 ± 3.3%. Linear regression analyses, adjusted for age, sex, vascular risk factors, intima media thickness and LI showed that in patients with moderate to severe WML (upper quartile) BPF was lower (–0.51%; 95% CI –0.93 to –0.08%), VF was higher (0.48%; 95% CI 0.31–0.65%) and GMF was lower (–1.48%; 95% CI –2.07 to –0.88%) than in patients with few WML (lower quartile). Presence of LI was associated with lower BPF (–0.52%; 95% CI –0.96 to –0.07%) and higher VF (0.25%; 95% CI 0.07–0.42%), but not with GMF, independent of WML and other potential confounders. Conclusion: WML are associated with total, subcortical and cortical brain atrophy, whereas LI are associated with total and subcortical atrophy, but not with cortical atrophy, suggesting an independent role for WML and LI in the pathogenesis of brain atrophy.

Objective To estimate brain volumes, white matter lesion (WML) volume and asymptomatic infarcts on MRI in a large cohort of patients with atherosclerotic disease. Methods Within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) study, a prospective cohort study on determinants and course of brain changes on MRI, cross-sectional analyses were performed in 1044 patients (mean age 58 ± 10 years, 80% male) with coronary artery disease, cerebrovascular disease, peripheral arterial disease, or abdominal aortic aneurysm. Brain segmentation was used to quantify volumes of cortical gray matter, white matter, sulcal and ventricular cerebrospinal fluid, and WML. All volumes were expressed relative to intracranial volume. Brain infarcts were rated visually and distinctions were made between cortical infarcts, large subcortical infarcts, lacunar infarcts, and infarcts in the cerebellum and brainstem. Results With older age a nonlinear (quadratic) decrease in total brain volume was observed and a nonlinear increase in ventricular volume and WML. Cortical gray matter volume showed a linear decrease with age and was stronger in men than in women. WML volumes also increased more strongly in men than in women, while ventricular volume decrease showed no sex difference. Silent brain infarcts were present in 14% of men and women, and increased to 24% of subjects aged 65 years or older. Conclusion In a population with atherosclerotic diseases, decrease in brain volumes with increasing age is comparable with findings from the general population. However, vascular pathology on MRI, as indicated by white matter lesions and silent brain infarcts may be more common.

To retrospectively investigate which characteristics are related to total arterial blood flow to the brain in patients with symptomatic vascular disease.The study was approved by the ethics committee of the authors' institution, and written informed consent was obtained. The total volume flow rate (tVFR) values in the internal carotid arteries and the basilar artery in 636 patients (536 men, 100 women; mean age, 58 years) with symptomatic vascular disease were measured with two-dimensional phase-contrast magnetic resonance (MR) angiography. Reference tVFR values in the general population were obtained from previous research involving 158 subjects (73 men, 85 women; mean age, 60 years).A higher tVFR was found in patients with symptomatic vascular disease, but this association was statistically significant in only those patients in the 7th decade of life. The mean tVFR decreased with increasing age (-3.4 mL/min per year; 95% confidence interval [CI]: -4.3, -2.5). Diabetes (-27.6 mL/min; 95% CI: -52.6, -2.6) and increasing body mass index (BMI) (-2.8 mL/min per BMI unit; 95% CI: -5.3, -0.2) were associated with lower tVFR. Patients with vascular disease in a cerebral location had lower tVFR values (-39.7 mL/min; 95% CI: -65.1, -14.3) than did patients with symptomatic vascular disease elsewhere in the vascular tree.Patients with symptomatic vascular disease had slightly higher arterial blood flow to the brain compared with the general population. The tVFR decreased with increasing age and increasing BMI, and patients with diabetes had lower tVFR values than did those without diabetes. Patients with vascular disease in a cerebral location had lower tVFR values than did those with symptomatic vascular disease at other arterial sites.