Joonsang Yoo

The frequency and risk of preclinical coronary artery disease detected using multichannel cardiac computed tomography in patients with ischemic stroke.

Background: Atherosclerosis is a systemic disease. Many ischemic stroke patients may have concomitant coronary artery disease (CAD). Detection and treatment of preclinical CAD in stroke patients may improve long-term outcome and survival because CAD is a major cause of death during follow-up in stroke patients. However, association between coronary and cerebral artery atherosclerosis in stroke patients has not fully been investigated. This study aimed at examining the frequency and high-risk groups of CAD in ischemic stroke patients. Methods: Consecutive patients who were admitted due to acute ischemic stroke between July 2006 and June 2010 were prospectively enrolled in this study. A total of 1,304 patients who underwent MSCT coronary angiography and cerebral angiography were included in this study. By using 64-multislice computed tomography coronary angiography, we investigated the frequency of CAD and association between coronary and cerebral artery atherosclerosis in terms of location and burden (severity and extent) in stroke patients. We also sought to identify high-risk groups for CAD among stroke patients. Results: The frequency of significant (≧50%) CAD was 32.3% and the frequency of any degree of CAD was 70.1%. Diabetes mellitus, serum levels of total cholesterol, high-density lipoprotein cholesterol and triglyceride, and significant stenosis of the extracranial carotid, intracranial vertebral and basilar arteries were independently associated with CAD. However, no association was found between CAD and significant stenosis of the anterior, middle and posterior cerebral arteries. The association between CAD and cerebral atherosclerosis was stronger with increased severity and extent of cerebral atherosclerosis. When compared to patients with <2 risk factors and without significant cerebral atherosclerosis, those with multiple (≧2) risk factors and atherosclerosis in both the carotid and the vertebrobasilar arteries had very high risks of CAD [odds ratio (OR) 8.36; 95% confidence interval (CI) 4.15–16.87]. The risk was also high in patients with multiple risk factors and atherosclerosis in either the carotid or the vertebrobasilar artery (OR 4.13; 95% CI 2.62–6.51), and in those with <2 risk factors but atherosclerosis in both the carotid and the vertebrobasilar arteries (OR 3.40; 95% CI 1.22–9.47). Conclusions: A substantial portion of stroke patients had preclinical CAD, and there was a clear relationship between coronary and cerebral artery atherosclerosis in terms of location and burden. The risk of CAD was particularly high in stroke patients with multiple risk factors and atherosclerosis of the carotid and/or vertebrobasilar arteries.

Stenting as a Rescue Treatment After Failure of Mechanical Thrombectomy for Anterior Circulation Large Artery Occlusion

Background and Purpose— We hypothesized that permanent stenting may be a rescue treatment for stentriever-failed anterior circulation large artery occlusion. We compared the outcomes among patients with permanent stenting and those without stenting after stentriever failure. Methods— We retrospectively evaluated 208 patients who underwent stentriever thrombectomy for anterior circulation large artery occlusion between September 2010 and September 2015. Modified thrombolysis in cerebral ischemia 2b-3 recanalization was achieved with stentriever alone or in combination with Penumbra device in 155 patients (74.5%). An additional 8 patients (3.8%) obtained modified thrombolysis in cerebral ischemia 2b-3 with urokinase or glycoprotein IIb/IIIa inhibitor infusion. Of the remaining 45 patients (21.6%), 17 underwent stenting (stenting group; mean age, 68 years), whereas 28 did not undergo stenting (nonstenting group; mean age, 72 years). The rate of modified thrombolysis in cerebral ischemia 2b-3 in stenting group was assessed, and clinical outcomes were compared between groups. Results— There were no differences in clinical and laboratory findings, initial National Institute of Health Stroke Scale score, location of anterior circulation large artery occlusion, and onset-to-puncture time between groups. Modified thrombolysis in cerebral ischemia 2b-3 was achieved in 14 members (83.3%) of the stenting group. Stenting group had more favorable outcomes (modified Rankin Scale score 0–2, 35.3%) and less cerebral herniation (11.8%) than nonstenting group (modified Rankin Scale score 0–2, 7.1%; cerebral herniation, 42.9%; P<0.05 for both). Symptomatic intracranial hemorrhage and mortality rates did not differ between stenting group (symptomatic intracranial hemorrhage, 11.8%; mortality, 23.5%) and nonstenting group (symptomatic intracranial hemorrhage, 14.3%; mortality, 39.3%). Conclusions— Permanent stenting may be a rescue modality for stentriever-failed anterior circulation large artery occlusion. A large prospective study is necessary for confirmation because of the small sample size of this study.

Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in Patients With Stroke and Mice

Background and Purpose— We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment. Methods— In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl3-induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement. Results— Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by <50% in 94 patients (55.0%, moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%, nonvolume reduction; either no change or thrombus volume increased), overall thrombus volume increased. The probability of thrombus resolution decreased as the time interval from symptom onset to treatment increased. On multivariate analysis, good volume reduction was independently related with shorter time intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute saved; 95% confidence interval, 0.974–0.999). In the mouse model, as the interval between thrombus formation and tPA treatment increased, the initiation of recanalization was delayed (P=0.006) and the frequency of final recanalization decreased (P for trends=0.006). Conclusions— Early administration of tPA after stroke onset is associated with better thrombus resolution.

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 mm3 vs. placebo: 0.3±1.3 mm3; 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.

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.

Computed Tomography-Based Thrombus Imaging for the Prediction of Recanalization after Reperfusion Therapy in Stroke

The prediction of successful recanalization following thrombolytic or endovascular treatment may be helpful to determine the strategy of recanalization treatment in acute stroke. Thrombus can be detected using noncontrast computed tomography (CT) as a hyperdense artery sign or blooming artifact on a T2*-weighted gradient-recalled image. The detection of thrombus using CT depends on slice thickness. Thrombus burden can be determined in terms of the length, volume, and clot burden score. The thrombus size can be quantitatively measured on thin-section CT or CT angiography/magnetic resonance angiography. The determination of thrombus size may be predictive of successful recanalization/non-recanalization after intravenous thrombolysis and endovascular treatment. However, cut-offs of thrombus size for predicting recanalization/non-recanalization are different among studies, due to different methods of measurements. Thus, a standardized method to measure the thrombus is necessary for thrombus imaging to be useful and reliable in clinical practice. Software-based measurements may provide a reliable and accurate assessment. The measurement should be easy and rapid to be more widely used in practice, which could be achieved by improvement of the user interface. In addition to prediction of recanalization, sequential measurements of thrombus volume before and after the treatment may also be useful to determine the efficacy of new thrombolytic drugs. This manuscript reviews the diagnosis of thrombus, prediction of recanalization using thrombus imaging, and practical considerations for the measurement of thrombus burden and density on CT.

Dose-Dependent Effect of Statin Pretreatment on Preventing the Periprocedural Complications of Carotid Artery Stenting

Background and Purpose— We investigated whether statin pretreatment can dose dependently reduce periprocedural complications in patients undergoing carotid artery stenting because of symptomatic carotid artery stenosis. Methods— We enrolled a consecutive series of 397 symptomatic carotid artery stenosis (≥50% stenosis on conventional angiography) treated with carotid artery stenting at 2 tertiary university hospitals over a decade. Definition of periprocedural complications included any stroke, myocardial infarction, and death within 1 month after or during the procedure. Statin pretreatment was divided into 3 categories according to the atorvastatin equivalent dose: none (n=158; 39.8%), standard dose (<40 mg of atorvastatin, n=155; 39.0%), and high dose (≥40 mg; n=84; 21.2%). A multivariable logistic regression analysis with the generalized estimating equation method was used to investigate independent factors in periprocedural complications. Results— The patients’ mean age was 68.7 years (81.6% men). The periprocedural complication rates across the 3 categories of statin use were 12.0%, 4.5%, and 1.2%. After adjustment, a change in the atorvastatin dose category was associated with reduction in the odds of periprocedural complications for each change in dose category (standard-dose statin: odds ratio, 0.24; 95% confidence interval, 0.07−0.81; high-dose statin: odds ratio, 0.11; 95% confidence interval, 0.01−0.96; P for trend=0.01). Administration of antiplatelet drugs was also an independent factor in periprocedural complications (OR, 0.18; 95% CI, 0.05−0.69). Conclusions— This study shows that statin pretreatment may reduce the incidence of periprocedural complications dose dependently in patients with symptomatic carotid artery stenting.

Predicting Asymptomatic Coronary Artery Diseasein Patients With Ischemic Stroke and Transient Ischemic Attack: The PRECORIS Score

Background and Purpose— Identifying occult coronary artery stenosis may improve secondary prevention of stroke patients. The aim of this study was to derive and validate a simple score to predict severe occult coronary artery stenosis in stroke patients. Methods— We derived a score from a French hospital–based cohort of consecutive patients (n=300) who had an ischemic stroke or a transient ischemic attack and no previous history of coronary heart disease (Predicting Asymptomatic Coronary Artery Disease in Patients With Ischemic Stroke and Transient Ischemic Attack [PRECORIS] score) and validated the score in a similar Korean cohort (n=1602). In both cohorts, severe coronary artery stenosis was defined by the presence of at least 1 ≥50% coronary artery stenosis as detected by 64-section CT coronary angiography. Results— A 5-point score (Framingham Risk Score–predicted 10-year coronary heart disease risk [≥20%=3; 10–19%=1; <10%=0] and cervicocephalic artery stenosis [≥50%=2; <50%=1; none=0]) was predictive of occult ≥50% coronary artery stenosis risk in the derivation cohort (C-statistic=0.77 [0.70–0.84]) and in the validation cohort (C-statistic=0.66 [0.63–0.68]). The predictive ability of the score was even stronger when only ≥50% left main trunk disease or 3-vessel disease were considered (C-statistic=0.83 [0.74–0.92] and 0.70 [0.66–0.74] in derivation and validation cohorts, respectively). The prevalence of occult ≥50% coronary artery stenosis and ≥50% left main trunk or 3-vessel disease increased gradually with the PRECORIS score, reaching 44.2% and 13.5% in derivation cohort and 49.8% and 12.8% in validation cohort in patients with a PRECORIS score ≥4. Conclusions— The PRECORIS score can identify a population of stroke or transient ischemic attack patients with a high prevalence of occult severe coronary artery stenosis.

Rescue Stenting for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Multicenter Experience

Background and Purpose— Effective rescue treatment has not yet been suggested in patients with mechanical thrombectomy (MT) failure. This study aimed to test whether rescue stenting (RS) improved clinical outcomes in MT-failed patients. Methods— This is a retrospective analysis of the cohorts of the 16 comprehensive stroke centers between September 2010 and December 2015. We identified the patients who underwent MT but failed to recanalize intracranial internal carotid artery or middle cerebral artery M1 occlusion. Patients were dichotomized into 2 groups: patients with RS and without RS after MT failure. Clinical and laboratory findings and outcomes were compared between the 2 groups. It was tested whether RS is associated with functional outcome. Results— MT failed in 148 (25.0%) of the 591 patients with internal carotid artery or middle cerebral artery M1 occlusion. Of these 148 patients, 48 received RS (RS group) and 100 were left without further treatment (no stenting group). Recanalization was successful in 64.6% (31 of 48 patients) of RS group. Compared with no stenting group, RS group showed a significantly higher rate of good outcome (modified Rankin Scale score, 0–2; 39.6% versus 22.0%; P=0.031) without increasing symptomatic intracranial hemorrhage (16.7% versus 20.0%; P=0.823) or mortality (12.5% versus 19.0%; P=0.360). Of the RS group, patients who had recanalization success had 54.8% of good outcome, which is comparable to that (55.4%) of recanalization success group with MT. RS remained independently associated with good outcome after adjustment of other factors (odds ratio, 3.393; 95% confidence interval, 1.192–9.655; P=0.022). Follow-up vascular imaging was available in the 23 (74.2%) of 31 patients with recanalization success with RS. The stent was patent in 20 (87.0%) of the 23 patients. Glycoprotein IIb/IIIa inhibitor was significantly associated with stent patency but not with symptomatic intracranial hemorrhage. Conclusions— RS was independently associated with good outcomes without increasing symptomatic intracranial hemorrhage or mortality. RS seemed considered in MT-failed internal carotid artery or middle cerebral artery M1 occlusion.

Comparison of Outcomes after Reperfusion Therapy between In-Hospital and Out-of-Hospital Stroke Patients

Background: Patients may experience stroke while being admitted to the hospital (in-hospital stroke (IHS)) and they may be important candidates for reperfusion therapy. IHS patients may have various comorbidities and show worse outcomes compared with patients with an out-of-hospital stroke (OHS). On the other hand, the time from onset to treatment may be shorter in IHS patients than OHS patients. Most outcome studies of reperfusion therapy have been based on findings in OHS patients, and little information is currently available regarding outcomes of IHS, whether the outcomes differ between patients with IHS and those with OHS who receive reperfusion therapy. Methods: This is a retrospective observational study using prospectively registered data. Consecutive patients who underwent the reperfusion therapy (intravenous (IV), intra-arterial (IA), or combined IV and IA) between July 2002 and June 2014 in a university hospital were included for this study. We compared the demographics, time interval from symptom onset to treatment, and outcomes between IHS and OHS patients and analyzed the factors associated with in-hospital mortality. Results: A total of 686 patients received the reperfusion therapy during the study period. Of them, 256 (37.3%) patients received the IV tissue plasminogen activator (t-PA) therapy only, 243 (35.4%) patients received the IA therapy only, and 187 (27.3%) patients received the combined IV and IA therapy. Among these, 104 (15.2%) were IHS patients. The time intervals from symptom onset to IV t-PA administration (87.5 ± 48.4 vs. 113.4 ± 38.3 min, p < 0.001) and IA puncture (221.8 ± 195.0 vs. 343.6 ± 155.4 min, p < 0.001) were shorter for IHS than OHS. The rates of successful recanalization and symptomatic intracerebral hemorrhage, and the favorable functional outcome at 3 months were similar between the groups. In-hospital all-cause mortality was higher in IHS than OHS (16.3 vs. 8.4%, p = 0.019), but after adjustment, IHS was not an independent factor. The stroke mortality did not differ between the groups (9.6 vs. 6.9%, p = 0.432). Conclusions: Although IHS patients more frequently had comorbid diseases and higher overall in-hospital mortality, the standard outcomes of the reperfusion therapy were similar between IHS and OHS patients, which might be, in part, ascribed to the shorter interval from symptom onset to treatment in IHS. Considering a substantial portion of IHS patients, we should pay more attention to these patients.