Takao Hoshino

Transient neurological attack before vertebrobasilar stroke

BACKGROUND Patients with vertebrobasilar (VB) circulation ischemia can present with nonspecific symptoms, which complicate the distinction of transient ischemic attack (TIA) from other benign disorders. According to previously accepted classifications, typical TIA does not occur with VB symptom such as vertigo, diplopia, or dysarthria in isolation. However, there is a lack of evidence to support this hypothesis. METHODS This hospital-based study included 214 consecutive patients with acute ischemic VB stroke. We defined transient neurological attacks (TNAs) as temporary (<24h) episodes with neurological symptoms, and further divided them into TIA, nonspecific TNA, or other specific disorder groups. We investigated the incidence and clinical symptoms of TNAs within 3months prior to the stroke episode, and comparisons were made between patients with and without previous TNA history with respect to their background and stroke profiles. RESULTS Among 214 patients with VB stroke, 56 (26.2%) had previous TNAs. Six of them were diagnosed with other specific disorders and excluded from the analysis. The remaining 33 and 17 were diagnosed with TIA and nonspecific TNA, respectively. Twenty-one (42.0%) had attacks with a nonfocal symptom in isolation, and acute infarction in neuroimaging was confirmed in 4 of these patients. Vertigo was the most frequent nonspecific TNA symptom. Patients with prior TNA had a significantly higher rate of atherothrombotic stroke than those without TNA (40.0% vs. 21.5%, P=0.009). CONCLUSIONS A considerable fraction of TIAs due to VB circulation ischemia may be overlooked among clinically nonfocal TNAs.

Prolonged QTc Interval Predicts Poststroke Paroxysmal Atrial Fibrillation

Background and Purpose— Paroxysmal atrial fibrillation (PAF) is often difficult to detect in patients with acute ischemic stroke. We aimed to assess the predictive value of a prolonged QT interval corrected for heart rate (QTc) in PAF detection after acute ischemic stroke. Methods— We enrolled 972 patients with acute ischemic stroke consecutively extracted from our observational stroke registry system. Exclusion criteria were as follows: (1) AF on the initial 12-lead ECG (n=171); (2) previously diagnosed PAF (n=47); and (3) the use of a cardiac pacemaker (n=10). Of the 972 patients, 744 (mean age, 67.6 years; men, 62.6%) were eligible for analysis. The clinical characteristics and 12-lead ECG findings of the patients with and without PAF were compared, and multiple logistic regression analysis was performed to identify predictors of poststroke PAF. Results— The poststroke cardiac work-up yielded 69 (9.3%) de novo PAF cases among the 744 patients. The QTc interval was significantly longer in patients with PAF than in those without PAF (436 versus 417 ms; P<0.001). Each 10-ms increase in the QTc interval was associated with an increased risk of PAF after multivariate adjustments (odds ratio, 1.41; 95% confidence interval, 1.24–1.61; P<0.001). The optimal threshold value of QTc interval calculated by a receiver-operating characteristic curve was 438 ms, and the area under the curve was 0.73 in this data set. Conclusions— The QTc interval prolongation is potentially a strong and useful predictor for poststroke PAF.

Clinical Features and Functional Outcome of Stroke After Transient Ischemic Attack

BACKGROUND Transient ischemic attacks (TIAs) greatly increase the risk of stroke, but few reports have examined subsequent stroke in patients with history of TIA. METHODS This retrospective, hospital-based study included 506 consecutive patients with acute ischemic stroke who were admitted to our hospital. The clinical features and prognosis were compared between patients with and without TIA. Multiple logistic regression analysis was also performed to identify predictors for poor outcome. RESULTS Of 506 patients, 114 (22.5%) had a history of TIA. Compared to patients without previous TIAs (non-TIA group), patients with previous TIAs (TIA group) were significantly more likely to have hypertension (76.3% vs 64.3%; P = .016), dyslipidemia (57.0% vs 41.1%; P = .003), chronic kidney disease (28.1% v 15.1%; P = .001), intracranial major artery stenosis (51.8% vs 36.2%; P = .018), and large artery atherothrombosis (43.9% vs 28.3%; P = .002). There was no difference in the previous use of antithrombotic medications between the groups (36.0% vs 35.2%; P = .881). Although stroke severity on admission was similar, poor functional outcome (modified Rankin Scale score ≥4) was significantly more frequent in the TIA group, and history of TIA was an independent determinant of unfavorable outcome on multiple logistic regression analysis (odds ratio 1.46; 95% confidence interval 1.02-2.10; P = .041). CONCLUSIONS Atherothrombotic stroke with concomitant vascular risk factors were more frequent in the stroke patients with than without previous TIA. Antithrombotic therapy was conducted only in one-third of the patients even after TIA. The stroke patients with history of TIA were at great risk of disabling stroke.

CHADS2 score predicts functional outcome of stroke in patients with a history of coronary artery disease

BACKGROUND The aim of this study was to evaluate the efficacy of the CHADS2 scoring system as a prognostic tool for stroke patients with a prior history of coronary artery disease (CAD). METHODS We enrolled 148 acute ischemic stroke patients (mean age, 74.2 years; males, 77.0%) with a history of CAD. Pre-admission CHADS2 scores were calculated by assigning a single point for the presence of congestive heart failure, hypertension, age ≥75 years, and diabetes; and assigning 2 points for a prior history of stroke or transient ischemic attack. Comparisons were made between patients with poor and good 3-month functional outcomes. A multivariate logistic regression analysis was performed to assess the predictive value of CHADS2 scores for poor outcome. RESULTS The patients with poor and good outcomes displayed significant differences in CHADS2 scores (median, 3 vs. 2, P=0.014), carotid artery stenosis (41.0% vs. 24.6%, P=0.037), intracranial artery stenosis (32.5% vs. 15.4%, P=0.017), atrial fibrillation (31.3% vs. 16.9%, P=0.045), and admission NIHSS score (median, 11 vs. 5, P<0.001). The CHADS2 score was an independent determinant of poor functional outcome on a multivariate analysis (per 1 point increase: OR 1.47, 95% CI 1.05-2.11, P=0.025; CHADS2 score ≥3: OR 1.58, 95% CI 1.01-2.54, P=0.050). CONCLUSIONS The CHADS2 score is a potential useful tool for predicting functional outcome in stroke patients with a history of CAD.

Cardioembolic Stroke is Frequent in Late Recurrence After Transient Ischemic Attack

BACKGROUND Transient ischemic attack (TIA) is often followed by a stroke episode. Differences between early and late recurrent stroke, however, have not been elucidated. METHODS We enrolled 133 consecutive patients with acute ischemic stroke who presented to our hospital and had previously been diagnosed with TIA. They were divided into 5 groups according to the interval between TIA and subsequent stroke: <48 hours (group 1); 48 hours to 1 week (group 2); 1 week to 1 month (group 3); 1 month to 3 months (group 4); and >3 months (group 5). Patients who underwent recurrent stroke within and after 1 week subsequent to TIA (the early and late recurrence groups, respectively) were compared with regard to clinical findings. RESULTS Of the 133 patients, 46 (34.6%) were in group 1, 29 (21.8%) in group 2, 23 (17.3%) in group 3, 18 (13.5%) in group 4, and 17 (12.8%) in group 5. Most of the noncardioembolic strokes were observed shortly after TIA, while the percentage of cardioembolic stroke remained high even after long post-TIA periods. The prevalence of atrial fibrillation (AF) was higher in the late recurrence group than in the early recurrence group (41.4% v 24.0%, P = .033). Among 42 patients with AF, 12 (28.6%) were newly diagnosed at the time of stroke. CONCLUSIONS The frequency of cardioembolic stroke did not decline as time after TIA passed. More than one quarter of AF patients had been asymptomatic before stroke, suggesting the need for repeated examinations to detect AF in patients with TIA of unknown etiology.

Ankle-brachial index and neurologic deterioration in acute ischemic stroke.

BACKGROUND Few studies have examined the relationship between abnormal ankle-brachial index (ABI) and short-term outcome in patients with acute ischemic stroke (AIS). METHODS We included 209 consecutive patients with AIS admitted to our hospital and divided them into abnormal ABI (≤.9) and normal ABI (>.9) groups. We defined neurologic deterioration (ND) as an increase of 1 or more points in the National Institutes of Health Stroke Scale score within 7 days of stroke onset. Clinical characteristics were compared between the 2 groups. Then, we performed a multiple logistic regression analysis to identify independent predictors of ND. In the multivariate analysis, the ABI values were used separately as binary variables in different cutoff thresholds (.9, 1.0, and 1.1). RESULTS Of the 209 patients, 24 (11.5%) had an abnormal ABI. The patients in abnormal and normal ABI groups showed significant differences in carotid arterial stenosis (37.5% versus 18.9%; P = .040), intracranial artery stenosis (54.2% versus 18.9%; P < .001), and previous use of antiplatelet drugs (58.3% versus 29.2%; P = .004). According to the multivariate analysis, ABIs of .9 or less and 1.0 or less were positively associated with ND (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.03-2.89; P = .034 and OR, 1.63; 95% CI, 1.05-2.54; P = .027, respectively), whereas an ABI value of 1.1 or less was not an independent predictor of ND (OR, 1.17; 95% CI, 0.79-1.74; P = .43). CONCLUSIONS Not only an ABI of .9 or less but also an ABI of 1.0 or less can be a predictor of ND in patients with AIS.

Prevalence of Systemic Atherosclerosis Burdens and Overlapping Stroke Etiologies and Their Associations With Long-term Vascular Prognosis in Stroke With Intracranial Atherosclerotic Disease

Importance Patients who have experienced stroke with intracranial atherosclerotic disease (ICAD) may also have concomitant atherosclerosis in different arterial beds and other possible causes for ischemic stroke. However, little is known about the frequency and prognostic effect of such overlapping diseases. Objectives To describe the prevalence of systemic atherosclerotic burdens and overlapping stroke etiologies and their contributions to long-term prognoses among patients who have experienced stroke with ICAD. Design, Setting, and Participants The Asymptomatic Myocardial Ischemia in Stroke and Atherosclerotic Disease study is a single-center prospective study in which 405 patients with acute ischemic stroke within 10 days of onset were consecutively enrolled between June 2005 and December 2008 and followed up for 4 years. After excluding 2 patients because of incomplete investigations, 403 were included in this analysis. Main Outcomes and Measures Significant ICAD was defined as having 50% or greater stenosis/occlusion by contrast-enhanced/time-of-flight magnetic resonance angiography, computed tomography angiography, and/or transcranial Doppler ultrasonography. Systemic vascular investigations on atherosclerotic disease were performed with ultrasonography in carotid arteries, aorta and femoral arteries, and by angiography in coronary arteries. Coexistent stroke etiologies were assessed using the atherosclerosis, small-vessel disease, cardiac pathology, other cause, and dissection (ASCOD) grading system. We estimated the 4-year risk of major adverse cardiovascular events (MACE), including vascular death, nonfatal cardiac events, nonfatal stroke, and major peripheral arterial events. Results Of 403 participants, 298 (74%) were men and the mean (SD) age was 62.6 (13.1) years. Significant ICAD was found in 146 (36.2%). Patients with significant ICAD more often had aortic arch (70 [60.9%] vs 99 [49.0%]; P = .04) and coronary artery (103 [76.9%] vs 153 [63.2%]; P = .007) atherosclerosis than those without. Among patients with ICAD, concurrent stenosis in the extracranial carotid artery (24 [23.4%] vs 3 [9.0%]; P = .08; adjusted hazard ratio[aHR] = 2.12) and the coronary artery (19 [29.9%] vs 8 [12.8%]; P = .01; aHR = 1.90) increased the MACE risk. Furthermore, patients with ICAD who also had any cardiac pathology (ASCOD grade C1-3) were at a higher MACE risk than others (grade C0) (20 [28.2%] vs 7 [11.4%]; P = .01; aHR = 2.24). By contrast, patients with ICAD with any form of small vessel disease (grade S1-3) had a lower MACE risk than those without (grade S0) (20 [17.3%] vs 6 [34.6%]; P = .05; aHR = 0.23). Conclusions and Relevance Patients with ICAD often have coexisting systemic atherosclerosis and multiple potential stroke mechanisms that affect their prognosis, suggesting that extensive evaluations of overlapping diseases may allow better risk stratification.

Brain Natriuretic Peptide Is a Powerful Predictor of Outcome in Stroke Patients with Atrial Fibrillation

Background: Since stroke patients with nonvalvular atrial fibrillation (NVAF) have poor outcomes in general, the prediction of outcomes following discharge is of utmost concern for these patients. We previously reported that brain natriuretic peptide (BNP) levels were significantly higher in NVAF patients with larger infarcts, higher modified Rankin Scale (mRS) score, and higher CHADS2 score. In the present study, we evaluated an array of variables, including BNP, in order to determine significant predictors for functional outcome in patients with NVAF after acute ischemic stroke (AIS). Methods: A total of 615 consecutive patients with AIS within 48 h of symptom onset, admitted to our hospital between April 2010 and October 2015, were retrospectively searched. Among these patients, we enrolled consecutive patients with NVAF. We evaluated the mRS score 3 months after onset of stroke and investigated associations between mRS score and the following clinical and echocardiographic variables. Categorical variables included male sex, current smoking, alcohol intake, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, peripheral artery disease, use of antiplatelet drugs, anticoagulants, or tissue plasminogen activator (tPA), and infarct size. Continuous variables included age, systolic blood pressure (SBP), diastolic blood pressure, hemoglobin, creatinine, D-dimer, brain natriuretic peptide (BNP), left atrial diameter, left ventricular ejection fraction (EF), and early mitral inflow velocity/diastolic mitral annular velocity (E/e’). We also analyzed the association of prestroke CHADS2, CHA2DS2-VASc, and R2CHADS2 scores, and National Institutes of Health Stroke Scale (NIHSS) score on admission with mRS score 3 months after the onset of stroke. Patients were classified into 2 groups according to mRS score: an mRS score ≤2 was defined as good outcome, an mRS score ≥3 was defined as poor outcome. To clarify the correlations between categorical or continuous variables and mRS score, uni- and multivariate logistic regression models using the stepwise variable selection method were applied. Results: Among 157 patients with NVAF after AIS, 63.7% were male and the mean age was 75.9 years. In univariate regression analysis, poor outcome (mRS score ≥3) was associated with use of tPA, infarct size, age, SBP, BNP, EF, and NIHSS score. In multivariate regression analysis, BNP levels (odds ratio [OR] 6.40; 95% confidence interval [CI] 1.26–32.43; p = 0.0235) and NIHSS score (OR 2.87; 95% CI 1.84–4.47; p < 0.001) were significantly associated with poor outcome (mRS score ≥3) after adjusting for use of tPA, infarct size, age, BNP, EF, and NIHSS score. Conclusions: Apart from NIHSS score, BNP was a very useful predictor for long-term outcomes of patients with NVAF after AIS.


Slow sinus heart rate as a potential predictive factor of paroxysmal atrial fibrillation in stroke patients.

Background: Paroxysmal atrial fibrillation (PAF) is a strong independent risk factor for ischemic stroke and is also associated with stroke severity and mortality. However, the detection rate of PAF in patients with ischemic stroke is limited because they are often asymptomatic or present with sinus rhythm on electrocardiograms (ECGs). In the present study, we aimed to identify predictors of PAF in stroke patients by continuous ECG monitoring of the heart rate in sinus rhythm. Methods: We enrolled 741 consecutive patients with acute symptomatic ischemic stroke who were admitted to our hospital. Exclusion criteria were the following: (1) patients with persistent AF, (2) cardiac pacemaker users and (3) incomplete clinical investigations. Each patient was subject to 24-hour Holter ECG, cardiac monitoring by inpatient telemetry and routine transthoracic echocardiography. The minimum and mean sinus heart rates (SHRs) on 24-hour Holter ECGs were recorded. The presence of PAF was judged on the basis of previous history and cardiac studies during hospitalization. Clinical characteristics of the patients with and without PAF were compared, and multiple logistic regression analysis was performed to identify the predictors of PAF. Results: Of all enrolled patients, 606 (mean age 68.2 years, 63.4% male) were eligible for analysis, and the presence of PAF was confirmed in 116 subjects (19.1%). In the univariate analysis, the patients with and without PAF showed significant differences in age (74.3 vs. 66.7 years, p < 0.001), dyslipidemia (32.8 vs. 50.4%, p = 0.001), chronic heart failure (16.4 vs. 4.7%, p < 0.001), admission National Institute of Health Stroke Scale score (8.5 vs. 6, p < 0.001) and absence of vascular etiology (80.2 vs. 54.1%, p < 0.001). Furthermore, the minimum and mean SHRs were slower in the patients with than in those without PAF (46.5 vs. 54.0 bpm, p < 0.001 and 70.7 vs. 73.8 bpm, p = 0.009, respectively). In 501 (82.7%) out of 606 patients, minimum SHRs were detected at night (from 9:00 p.m. to 7:00 a.m.). A minimum SHR was an independent predictive factor of PAF in the multivariate analysis (odds ratio 1.08, 95% confidence interval 1.05 - 1.12, p < 0.001). Conclusions: A slow SHR on monitoring ECG is a potential predictive factor of PAF in patients with ischemic stroke.

Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org

Background and Purpose— This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians. Methods— The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. Results— Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63–0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD2 score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians. Conclusions— The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.