Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial.

BACKGROUND: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 µg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. METHODS: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. RESULTS: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2-2.6). Median time from baseline CT to study drug was 62.5 (55-80) minutes, and from study drug to early post-dose CT was 19 (14.5-30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (-0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8-8.3) in the placebo arm (P=0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (-2.6 to 8.3) in the rFVIIa arm and 0.7 mL (-1.6 to 2.1) in the placebo arm (P=0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71-1.43]; P=0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994-1.003]; P=0.50; Table 3). CONCLUSIONS: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01359202.

Cerebral Infarction Observed on Brain MRI in Unconscious Out-of-Hospital Cardiac Arrest Survivors: A Pilot Study.

BACKGROUND: Cumulative evidence regarding the use of brain magnetic resonance imaging (MRI) for predicting prognosis of unconscious out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM) is available. Theoretically, these patients are at a high risk of developing cerebral infarction. However, there is a paucity of reports regarding the characteristics of cerebral infarction in this population. Thus, we performed a pilot study to identify the characteristics and risk factors of cerebral infarction and to evaluate whether this infarction is associated with clinical outcomes. METHODS: A single-center, retrospective, registry-based cohort study was conducted at Severance Hospital, a tertiary center. Unconscious OHCA survivors were registered and treated with TTM between September 2011 and December 2015. We included patients who underwent brain MRI in the first week after the return of spontaneous circulation. We excluded patients who underwent any endovascular interventions to focus on "procedure-unrelated" cerebral infarctions. We assessed hypoxic-ischemic encephalopathy (HIE) and procedure-unrelated cerebral infarction separately on MRI. Patients were categorized into the following groups based on MRI findings: HIE (-)/infarction (-), infarction-only, and HIE (+) groups. Conventional vascular risk factors showing p < 0.05 in univariate analyses were entered into multivariate logistic regression. We also evaluated if the presence of this procedure-unrelated cerebral infarction lesion or HIE was associated with a poor clinical outcome at discharge, defined as a cerebral performance category of 3-5. RESULTS: Among 71 unconscious OHCA survivors who completed TTM, underwent MRI, and who did not undergo endovascular interventions, 14 (19.7%) patients had procedure-unrelated cerebral infarction based on MRI. Advancing age [odds ratio (OR) 1.11] and atrial fibrillation (OR 5.78) were independently associated with the occurrence of procedure-unrelated cerebral infarction (both p < 0.05). There were more patients with poor clinical outcomes at discharge in the HIE (+) group (88.1%) than in the infarction-only (30.0%) or HIE (-)/infarction (-) group (15.8%) (p < 0.001). HIE (+) (OR 38.69, p < 0.001) was independently associated with poor clinical outcomes at discharge, whereas infarction-only was not (p > 0.05), compared to HIE (-)/infarction (-). CONCLUSIONS: In this pilot study, procedure-unrelated cerebral infarction was noted in approximately one-fifth of unconscious OHCA survivors who were treated with TTM and underwent MRI. Older age and atrial fibrillation might be associated with the occurrence of procedure-unrelated cerebral infarction, and cerebral infarction was not considered to be associated with clinical outcomes at discharge. Considering that the strict exclusion criteria in this pilot study resulted in a highly selected sample with a relatively small size, further work is needed to verify our findings.

Coronary Calcium Score for the Prediction of Asymptomatic Coronary Artery Disease in Patients With Ischemic Stroke.

Purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). However, it remains unclear which stroke patients should undergo evaluation for asymptomatic CAD, and which screening tools are appropriate. We investigated the role of coronary artery calcium (CAC) score as a screening tool for asymptomatic but severe CAD in acute stroke patients. We determined the selection criteria for CAC screening based on risk factors and cerebral atherosclerosis. Materials and Methods: The present study included consecutive patients with acute stroke who had undergone cerebral angiography and multi-detector computed tomography coronary angiography. Severe CAD was defined as left main artery disease or three-vessel disease. Enrolled patients were randomly assigned to two sets; a set for developing selection criteria and a set for validation. To develop selection criteria, we identified associated factors with severe CAD regarding clinical factors and cerebral atherosclerosis. CAD predictability of selection criteria with the CAC score was calculated. Results: Overall, 2,658 patients were included. Severe CAD was present in 360 patients (13.5%). CAC score was associated with CAD severity (P < 0.001). In the development set (N = 1,860), severe CAD was associated with age >65 years [odds ratio (95% confidence interval), 2.62 (1.93-3.55)], male sex (1.81 [1.33-2.46]), dyslipidemia (1.77 [1.25-2.61]), peripheral artery disease (2.64 [1.37-5.06]) and stenosis in the cervicocephalic branches, including the internal carotid (2.79 [2.06-3.78]) and vertebrobasilar arteries (2.08 [1.57-2.76]). We determined the combination of clinical and arterial factors as the selection criteria for CAC evaluation. The cut-off criterion was two or more elements of the selection criteria. The area under the curve (AUC) of the selection criteria was 0.701. The AUC significantly improved to 0.836 when the CAC score was added (P < 0.001). In the validation set (N = 798), the AUC of the selection criteria only was 0.661, and that of the CAC score was 0.833. The AUC of the selection criteria + CAC score significantly improved to 0.861(P < 0.001). Conclusion: The necessity for CAC evaluation could be determined based on the presence of risk factors and significant stenosis of the cervicocephalic arteries. CAC evaluation may be useful for screening for severe CAD in stroke patients.

Thrombus Volume as a Predictor of Nonrecanalization After Intravenous Thrombolysis in Acute Stroke.

Background and Purpose- We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods- This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results- In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm3; P<0.001). In the multivariate analysis, thrombus volume was independently associated with nonrecanalization ( P<0.001). The cutoff for predicting nonrecanalization was calculated as 200 mm3. In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions- Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Infarct Core Expansion on Computed Tomography before and after Intravenous Thrombolysis.

PURPOSE: Infarct core can expand rapidly in acute stroke patients receiving intravenous tissue plasminogen activator (IV t-PA). We investigated changes in the extent of infarct core during IV t-PA treatment, and explored the associative factors of this infarct core expansion in patients with proximal artery occlusion. MATERIALS AND METHODS: We included patients who were considered for sequential intra-arterial therapy (IAT) due to occlusion of intracranial proximal artery after IV t-PA. Patients who had a baseline Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) ≥6 and who underwent two consecutive CT scans before and shortly after IV t-PA infusion were enrolled. Patients were classified into no, moderate, and marked expansion groups based on decreases in ASPECTS (0-1, 2-3, and ≥4, respectively) on follow-up CT. Collateral status was graded using CT angiography. RESULTS: Of the 104 patients, 16 (15.4%) patients showed moderate and 13 (12.5%) patients showed marked infarct core expansion on follow-up CT scans obtained at 71.1±19.1 min after baseline CT scan. Sixteen (15.4%) patients had an ASPECTS value <6 on the follow-up CT. None of the patients with marked expansion were independent at 3 months. Univariate analysis and ordinal logistic regression analysis demonstrated that the infarct core expansion was significantly associated with collateral status (p<0.001). CONCLUSION: Among patients who were considered for IAT after IV t-PA treatment, one out of every seven patients exhibited marked expansion of infarct core on follow-up CT before IAT. These patients tend to have poor collaterals and poor outcomes despite rescue IAT.

Different infarction patterns in patients with aortic atheroma compared to those with cardioembolism or large artery atherosclerosis.

Aortic atheroma is a known cause of ischemic stroke. However, it is unclear whether ischemic stroke is caused by emboli from aortic atheroma or by accompanying atherosclerosis. In this study, we evaluated lesion patterns of patients with complex aortic plaque (CAP) to assume the underlying pathophysiology. Acute ischemic stroke patients who underwent transesophageal echocardiography were included. CAP was defined as a plaque in the proximal aorta ≥ 4 mm thick or with a mobile component. The diffusion-weighted imaging lesion patterns of patients with CAP were compared to those with large arterial atherosclerosis (LAA) or cardioembolism (CE). A total of 64 CAP patients, 127 LAA patients, and 80 CE patients were included. Small cortical pattern was more common in the CAP group (45.3%) than in the LAA (7.9%, p < 0.001) or the CE group (23.8%, p = 0.018). A large cortical pattern was more common in the CE group than in the CAP group (p < 0.001), whereas subcortical only pattern tended to be more common in the CAP group than in the CE group (p = 0.057). In multinominal analysis, the CAP group was more likely to have a small cortical lesion than the LAA group [odds ratio (OR) 14.63; 95% confidence interval (CI) 4.67-45.85] or the CE (OR 3.69, 95% CI 1.19-11.39) group. In conclusion, patients with CAP frequently had small cortical lesions or subcortical single lesion. These findings imply that ischemic stroke in aortic atheroma patients is associated with either small emboli or small artery disease.

Predictive value of thrombus volume for recanalization in stent retriever thrombectomy.

This retrospective study investigated whether the volume or density of the thrombus is predictive of recanalization in stent retriever (SR) treatment. Consecutive patients treated with SR thrombectomy as the first endovascular modality were enrolled. The thrombus volume and density were measured on thin-section noncontrast computed tomography using 3-dimensional software. The patients were grouped by recanalization status and the number of SR passes. Among 165 patients, recanalization was achieved with the first pass in 68 (50.0%), 2-3 passes in 43 (31.6%), and ≥4 passes in 25 (18.4%) patients. The thrombus volume was smaller in patients with (107.5 mm3) than without (173.7 mm3, p = 0.025) recanalization, and tended to be larger with increasing number of passes (p for trend = 0.001). The thrombus volume was an independent predictor of first-pass recanalization (odds ratio 0.93 per 10 mm3, 95% confidence interval 0.89-0.97). However, the thrombus density was not associated with recanalization success. Recanalization within 3 passes was associated with a favorable outcome. In conclusion, the thrombus volume was significantly related to recanalization in SR thrombectomy. Measuring the thrombus volume was particularly predictive of first-pass recanalization, which was associated with a higher likelihood of a favorable outcome.

The Protective Effect of Middle Cerebral Artery Calcification on Symptomatic Middle Cerebral Artery Infarction.

BACKGROUND AND PURPOSE: The presence of intracranial artery calcification is associated with an increased risk for stroke. However, calcified atherosclerotic plaques are also known to be less vulnerable to rupture. Given this discrepancy, we investigated whether the vulnerability of intracranial arterial atherosclerosis differed based on the presence or absence of calcification. METHODS: We considered consecutive patients with acute stroke in the unilateral middle cerebral artery (MCA) territory. Patients with any stenotic MCAs were included in this study. Symptomatic MCA was defined as the occurrence of infarctions relevant to the stenotic MCA. The presence of calcification in the MCA was evaluated on noncontrast thin-section computed tomography images using a 3dimensional software package. Generalized estimating equations were used to compare the frequency of calcification between symptomatic and asymptomatic stenosis. RESULTS: Of the 1066 MCAs examined in 533 patients, 645 MCAs were stenotic and were included in the study. Among the 645 stenotic MCAs, 406 MCAs (62.9%) were symptomatic. Calcification was observed in 36 MCAs (5.6%). Calcification in the MCA was more frequently observed in the asymptomatic group (7.9% versus 4.2%; P=0.032). On multivariable analysis, the presence of calcification in MCA atherosclerosis was less frequent in the symptomatic group (odds ratio, 0.46; 95% confidence interval, 0.23-0.92; P=0.027). CONCLUSIONS: This study showed that calcified atherosclerosis in the MCA was less frequently symptomatic.

Poor long-term outcomes in stroke patients with asymptomatic coronary artery disease in heart CT.

BACKGROUND AND AIMS: Although stroke patients have a high risk of ischemic heart disease, little information is available on the risk of coronary events in stroke patients with asymptomatic coronary artery disease (CAD). We investigated the long-term vascular outcomes in stroke patients with asymptomatic CAD diagnosed with multi-detector coronary computed tomography (MDCT). METHODS: This study was a retrospective analysis using a prospective cohort of ischemic stroke patients. We included consecutive stroke patients without history or symptoms of CAD who underwent MDCT. We investigated the long-term risk of major adverse cardiovascular events (MACE: cardiovascular mortality, ischemic stroke, myocardial infarction, unstable angina, and urgent coronary revascularization) and composite of MACE/all-cause mortality/elective coronary revascularization. We further investigated the value of MDCT for MACE prediction. RESULTS: Among the 1893 included patients, 1349 (71.3%) patients had some degree of CAD and 654 patients (34.5%) had significant (≥50%) CAD. At follow-up (median, 4.4 years), MACE occurred in 230 patients (12.2%). Event rates of MACE increased with the increasing extent of CAD. After adjustment for age, sex, and risk factors, the hazard ratios for MACE in mild CAD, 1-VD, 2-VD, and 3-VD or left main coronary disease were 1.28 (95% confidence interval [CI]: 0.88-1.87), 1.39 (95% CI: 0.90-2.16), 2.22 (95% CI: 1.39-3.55), and 2.91 (95% CI: 1.82-4.65), respectively (no CAD as a reference). Diagnosis of asymptomatic CAD significantly improved the prediction of MACE. CONCLUSIONS: Asymptomatic CAD detected on MDCT was associated with increased risks of vascular events or deaths in acute stroke patients.

Total Cerebral Small-Vessel Disease Score is Associated with Mortality during Follow-Up after Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The recently developed total cerebral small-vessel disease (CSVD) score might appropriately reflect the total burden or severity of CSVD. We investigated whether the total CSVD score is associated with long-term outcomes during follow-up in patients with acute ischemic stroke. METHODS: In total, 1,096 consecutive patients with acute ischemic stroke who underwent brain magnetic resonance imaging were enrolled. We calculated the total CSVD score for each patient after determining the burden of cerebral microbleeds (CMBs), high-grade white-matter hyperintensities (HWHs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and cause of death for all of the patients using data from the Korean National Statistical Office. We compared the long-term mortality rate with the total CSVD score using Cox proportional-hazards models. RESULTS: CMBs were found in 26.8% of the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096), and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that were significant at p<0.1 in the univariate analysis, the total CSVD score was independently associated with long-term death from all causes [hazard ratio (HR)=1.18 per point, 95% confidence interval (CI)=1.07-1.30], ischemic stroke (HR=1.20 per point, 95% CI=1.01-1.42), and hemorrhagic stroke (HR=2.05 per point, 95% CI=1.30-3.22), but not with fatal cardiovascular events (HR=1.17 per point, 95% CI=0.82-1.67). CONCLUSIONS: The total CSVD score is a potential imaging biomarker for predicting mortality during follow-up in patients with acute ischemic stroke.

Liver fibrosis assessed with transient elastography is an independent risk factor for ischemic stroke.

BACKGROUND AND AIMS: The relationship between liver fibrosis and the occurrence of ischemic stroke is unknown. We investigated the correlation between liver fibrosis assessed with transient elastography (TE) and the risk of ischemic stroke. METHODS: Between April 2013 and August 2014, patients with acute ischemic stroke and subjects who underwent a health check-up were included in the study. Liver fibrotic burden was assessed with TE in all participants. The degree of liver fibrosis was compared between groups by using various multiple logistic regression models and propensity-score matched analyses. RESULTS: Two hundred ninety-five patients with ischemic stroke (stroke group) and 1942 subjects with health check-up (control group) were included. The mean liver stiffness (LS) on TE (5.6 vs. 4.1 kPa) and the proportion of significant fibrosis (>8 kPa) (9.2% vs. 1.8%) were significantly higher in the stroke than in the control group (all p<0.05). These trends were observed regardless of body mass index, the degree of hepatic steatosis, and metabolic syndrome (all p<0.05). The adjusted odds ratio (OR) for ischemic stroke was 1.268 (95% confidence intervals [CI] 1.183-1.358) per 1 kPa increase and 12.033 (95% CI 5.180-27.948) for significant fibrosis, compared with no fibrosis (all p < 0.05). Propensity-score matched analysis also confirmed that liver fibrosis was independently associated with the risk of ischemic stroke (OR 1.804 [95% CI 1.461-2.230] per 1 kPa increase, 13.184 [95% CI 3.127-55.645] for significant fibrosis, compared with no fibrosis; all p<0.001). CONCLUSIONS: The degree of liver fibrosis, assessed with TE, was significantly associated with the risk of ischemic stroke.

Increased Risk of Cardiovascular Events in Stroke Patients Who had Not Undergone Evaluation for Coronary Artery Disease.

PURPOSE: Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not. MATERIALS AND METHODS: This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (-) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses. RESULTS: During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (-) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (-) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172-8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (-) group seemed to also have a higher risk of recurrent stroke. CONCLUSION: Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up.

Lenticulostriate Artery Involvement is Predictive of Poor Outcomes in Superficial Middle Cerebral Artery Territory Infarction.

PURPOSE: Patients with superficial middle cerebral artery (MCA) territory infarction may have concomitant lenticulostriate artery (LSA) territory infarction. We investigated the mechanisms thereof and the outcomes of patients with superficial MCA territory infarction according to the presence or absence of LSA involvement. MATERIALS AND METHODS: Consecutive patients with first-ever infarction in the unilateral superficial MCA territory were included in this study. They were divided into the superficial MCA only (SM) group and the superficial MCA plus LSA (SM+L) group. RESULTS: Of the 398 patients, 84 patients (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had significant stenosis of the proximal MCA or carotid artery and high-risk cardioembolic sources. Stroke severity and outcomes were remarkably different between the groups. The SM+L group showed more severe neurologic deficits (National Institute of Health Stroke Scale score 10.8±7.1 vs. 4.0±5.0, p<0.001) and larger infarct in the superficial MCA territory (40.8±62.6 cm³ vs. 10.8±21.8 cm³, p<0.001) than the SM group. A poor functional outcome (mRS >2) at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p<0.001). During a mean follow-up of 26 months, 67 patients died. All-cause (hazard ratio, 2.246) and stroke (hazard ratio, 9.193) mortalities were higher in the SM+L group than the SM group. In multivariate analyses, LSA involvement was an independent predictor of poor functional outcomes and stroke mortality. CONCLUSION: LSA territory involvement is predictive of poor long-term outcomes in patients with superficial MCA territory infarction.

Prognostic value of urine dipstick proteinuria on mortality after acute ischemic stroke.

BACKGROUND AND AIMS: Proteinuria is a marker of kidney disease and a strong risk factor for cardiovascular diseases including stroke. This study was aimed at investigating the prognostic value of proteinuria measured by urine dipstick in patients with acute ischemic stroke. METHODS: This post-hoc analysis of a prospective cohort study included 3404 consecutive patients who had been admitted for acute ischemic stroke between November 2005 and June 2013. Proteinuria was defined as a trace or more of protein on a urine dipstick test routinely performed at admission. Date and cause of death until December 31, 2013 were collected. We investigated the association of proteinuria with all-cause mortality, cardiovascular mortality (defined as ICD-10 codes I00-I99), and non-cardiovascular mortality. RESULTS: Proteinuria was present in 12.8% of the 3404 patients. During the mean follow-up period of 3.56 ± 2.22 years, there were 681 cases of all-cause mortality (460 cardiovascular deaths and 221 non-cardiovascular deaths). Multivariate Cox regression analysis showed that the presence of proteinuria was an independent risk factor for all-cause mortality (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.40-2.04), cardiovascular mortality (adjusted HR 1.65, 95% CI 1.31-2.08), and non-cardiovascular mortality (adjusted HR 1.59, 95% CI 1.13-2.23). Adding proteinuria to the multivariate Cox models moderately improved the model performance for all-cause mortality (integrated area under curve [95% CI]: from 0.800 [0.784-0.816] to 0.803 [0.788-0.818], p = 0.026). CONCLUSIONS: Proteinuria, which was detected on a urine dipstick test, was a significant predictor of mortality after acute ischemic stroke.

Importance of truncal-type occlusion in stentriever-based thrombectomy for acute stroke.

OBJECTIVE: To investigate whether angiographically defined occlusion type could predict of the etiology of acute intracranial large artery occlusion and the stentriever response. METHODS: We reviewed consecutive patients with acute intracranial large artery occlusion who underwent endovascular treatment and examined their workups for embolic sources. Patient demographics, laboratory findings, hyperdense artery sign, and angiographic occlusion type (truncal-type or branching-site occlusion) were compared between embolic sources (+) and (-) groups. These variables were also compared between stentriever failure and success groups. Details of endovascular procedures were also compared according to occlusion type. RESULTS: A total of 259 patients (mean age 70.3 years; M:F = 132:127) were finally included. Of these patients, 216 (83.4%) were assigned to the embolic sources (+) group after thorough evaluation. Young age, no coronary artery disease, and truncal-type occlusion (odds ratio [OR] 9.07; 95% confidence interval [CI] 3.74-22.0) were independently associated with the embolic source (-) group. Of the overall group, 224 patients (86.5%) underwent stentriever-based endovascular treatment. Hypertension, diabetes, high C-reactive protein level, and truncal-type occlusion (OR 32.2; 95% CI 7.78-133.0) were independent predictors of stentriever failure. Truncal-type occlusion was associated with more reocclusion (77.3% vs 5.0%), resulting in recanalization failure by the stentriever (81.8% vs 20.3%), a longer puncture-to-recanalization time (118.0 vs 49.5 minutes), and more rescue treatment for final successful recanalization (78.9% vs 7.0%). CONCLUSIONS: Angiographic occlusion type is an independent predictor of stentriever refractoriness and of the underlying stroke mechanism.

Association between Aortic Atheroma and Cerebral Small Vessel Disease in Patients with Ischemic Stroke.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke. METHODS: We included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated. RESULTS: AA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75). CONCLUSIONS: In this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients.

Poor Outcome of Stroke Patients With Atrial Fibrillation in the Presence of Coexisting Spontaneous Echo Contrast.

BACKGROUND AND PURPOSE: Spontaneous echo contrast (SEC) is frequently detected in patients with atrial fibrillation (AF). Coexisting SEC in patients with AF may be associated with heightened thrombogenicity, which affects stroke outcomes. METHODS: Consecutive stroke patients with nonvalvular AF who underwent transesophageal echocardiography were included in this study. We compared initial stroke severity and functional outcome at 3 months between the patients with and those without SEC. RESULTS: Of 440 patients with nonvalvular AF who underwent transesophageal echocardiography during a 7-year period, 193 (43.9%) patients had SEC. Stroke was more severe in the patients with SEC than in those without SEC (National Institute of Health Stroke Scale score: median [interquartile range], 5 [2-12] versus 3 [1-8]; P=0.004). The patients with SEC more frequently had poor functional outcomes (modified Rankin scale score of >2) at 3 months than those without SEC (32.3% versus 16.1%; P<0.001). On multivariate analysis, the presence of SEC was an independent factor of poor outcome (odds ratio, 2.09; 95% confidence interval, 1.24-3.53). CONCLUSIONS: In the ischemic stroke patients with nonvalvular AF, coexisting SEC was associated with more severe stroke and was predictive of poor long-term functional outcome.

Comprehensive code stroke program to reduce reperfusion delay for in-hospital stroke patients.

BACKGROUND: Stroke may occur during hospital admission (in-hospital stroke). Although patients with in-hospital stroke are potentially good candidates for reperfusion therapy, they often do not receive treatment as rapidly as expected. AIMS: We investigated the effect of a code stroke program for in-hospital stroke, which included the use of computerized physician order entry, specific evaluation and treatment protocols for in-hospital stroke patients, and regular education of medical staffs. METHODS: We implemented the program in the cardiology and cardiovascular surgery departments/wards (target-ward group) in November 2008. We compared time intervals from symptom onset to evaluation and reperfusion treatment before and after program implementation between the target-ward and other departments/wards (other-ward group). RESULTS: Among 70 consecutive in-hospital stroke patients who received reperfusion therapy between July 2002 and February 2015, 28 and 42 were treated before and after program implementation, respectively. After program implementation, time intervals from symptom onset to neurology notification (50 min vs. 28 min; P = 0.033), symptom onset to brain imaging (91 min vs. 41 min; P < 0.001), and symptom recognition to notification (22 min vs. 9 min; P = 0.011) were reduced in the target-ward group. Finally, times from symptom onset to intravenous tissue plasminogen activator administration and to arterial puncture were reduced by 55 min (120 min vs. 65 min; P < 0.001) and 130 min (295 min vs. 165 min; P < 0.001), respectively. However, time reductions in the other-ward group were not significant. CONCLUSIONS: The comprehensive program for in-hospital stroke that included the use of computerized physician order entry was effective in reducing time intervals to evaluation and reperfusion therapy.

Effect and Safety of Rosuvastatin in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. METHODS: This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. RESULTS: This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53-1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm(3) vs. placebo: 0.3±1.3 mm(3); P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. CONCLUSIONS: The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.