Practical "1-2-3-4-Day" Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study.

BACKGROUND: The "1-3-6-12-day rule" for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. METHODS: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0-7), moderate (8-15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. RESULTS: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)-initiating DOACS within 1, 2, 3, and 4 days, respectively-than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27-0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27-0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. CONCLUSIONS: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Bridging Therapy With Heparin Before Starting Rivaroxaban in Ischemic Stroke or Transient Ischemic Attack With Non-Valvular Atrial Fibrillation.

BACKGROUND: The present observational study aimed to clarify the association between bridging therapy with heparin before starting rivaroxaban and clinical outcomes after ischemic stroke or transient ischemic attack (TIA) in patients with non-valvular atrial fibrillation (NVAF).Methods and Results: Patients with NVAF who experienced acute ischemic stroke or TIA of the middle cerebral artery territory and started rivaroxaban within 30 days after onset were enrolled and were followed up for 90 days. Outcome measures were ischemic events, major bleeding, their composite, and death or disability 90 days after onset. Ischemic events were defined as ischemic stroke, TIA, and systemic embolism. Of 1,308 analyzed patients, 638 received bridging therapy with unfractionated or low-molecular-weight heparin with a median of 10,000 IU/day. Associations between bridging therapy and ischemic events or major bleeding were not statistically significant individually, but the association between bridging therapy and their composite was statistically significant (multivariable-adjusted hazard ratio, 1.80; 95% confidence interval, 1.01-3.29). The association between bridging therapy and death or disability 90 days after onset was not statistically significant. CONCLUSIONS: The composite of ischemic events and major bleeding was more frequent in patients with NVAF who received bridging therapy with low-dose heparin than in those who started treatment directly with rivaroxaban after ischemic stroke or TIA.

Blood Pressure Level and Variability During Long-Term Prasugrel or Clopidogrel Medication After Stroke: PRASTRO-I.

BACKGROUND AND PURPOSE: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. METHODS: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. RESULTS: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094-1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010-1.466]), hemorrhagic stroke (13 events, 3.247 [1.660-6.296]), ischemic events (142 events, 1.219 [1.020-1.466]), and bleeding events (47 events, 1.629 [1.172-2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220-4.225] per 10-mm Hg increase; 3.051 [2.179-4.262]; 3.276 [1.172-9.092]; 2.865 [2.042-4.011]; 2.764 [1.524-5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. CONCLUSIONS: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp; Unique identifier: JapicCTI-111582.

Sex Differences in Management and Outcomes of Cardioembolic Stroke: Post HOC Analyses of the RELAXED Study.

INTRODUCTION: Experimental models have clearly demonstrated sex differences in the pathophysiology of stroke and prognosis, however clinical evidence remains elusive. In this study, we examined sex differences as a post hoc analysis of RELAXED (Recurrent Embolism Lessened by rivaroxaban, an anti-X agent, of Early Dosing for acute IS and TIA with atrial fibrillation) Study. METHODS: We stratified study participants by sex and compared baseline and clinical characteristics as well as clinical outcomes. The primary outcome measure was a good outcome defined as a modified Rankin Scale score of 0-2 at 90 days after stroke. Secondary outcomes were mortality at 90 days, intracranial hemorrhage within 90 days, and recurrence of stroke or transient ischemic attack within 90 days. We constructed a logistic regression model to estimate the adjusted odds ratio of female patients compared with male patients for the primary and secondary outcomes. RESULTS: Of 1303 patients, most were male (57.7%) with a mean age of 74.5 years. Female patients were older with a mean age of 80.6 ± 8.9 years and had significantly less frequent anticoagulation therapy before onset of stroke and more severe NIHSS scores. Good outcome was observed in 51.2% and 63.3% of the females and males (p < 0.0001). The adjusted odds ratio of a good outcome in females was 1.12 (95% confidence interval, 0.44-2.87) (p = 0.81). There were no sex differences in secondary outcomes. CONCLUSION: Adjusted regression analysis found no sex difference in the treatment outcomes at 90 days after stroke with non-valvular atrial fibrillation.

ASPECTS-Region-Dependent Functional Outcomes after Endovascular Therapy in Patients with Cardioembolic Stroke.

OBJECTIVES: Cardioembolic stroke has a poor prognosis. We evaluated the region-dependent efficacy of endovascular therapy (EVT) based on diffusion-weighted imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS). METHODS: This post-hoc analysis of the RELAXED study, which investigated the optimal timing of rivaroxaban to prevent nonvalvular atrial fibrillation (NVAF) recurrence in patients with acute ischemic stroke (AIS), included NVAF patients admitted with AIS or transient ischemic attack in the middle cerebral artery (MCA), with internal carotid artery (ICA), M1, or M2-MCA occlusion. Relationships between DWI-ASPECTS region and functional outcome (modified Rankin Scale [mRS]), mortality, recurrence, and hemorrhagic stroke were compared between patients with and without EVT, and adjusted odds ratios for age, pre-stroke mRS, National Institutes of Health Stroke Scale (NIHSS), ICA occlusion, infarct size, recombinant tissue plasminogen activator (rt-PA) use, and onset-to-hospitalization time were estimated. RESULTS: EVT patients had significantly lower hemoglobin levels, higher median NIHSS scores, more lentiform nucleus infarcts, ICA or M1-MCA occlusions, treatment with rt-PA, and fewer M3, M5, or M6 infarcts and M2-MCA occlusions than no-EVT patients. EVT patients had shorter onset-to-hospitalization times and more frequent favorable functional outcomes (p=0.007). Mortality, recurrent ischemic stroke, and hemorrhagic infarction were similar in both groups. EVT was associated with significantly better functional outcomes among patients with insular ribbon (p=0.043) and M3 (p=0.0008) infarcts. M3 patients had significantly fewer rt-PA and EVT, and longer onset-to-hospitalization times. CONCLUSIONS: An occlusion in the insular ribbon or M3 region was associated with favorable functional outcomes in patients treated with EVT after cardioembolic stroke.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730.

Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome.

BACKGROUND: We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). METHODS AND RESULTS: This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. CONCLUSIONS: IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Design and Rationale of the RELAXED (Recurrent Embolism Lessened by rivaroxaban, an Anti-Xa agent, of Early Dosing for acute ischemic stroke and transient ischemic attack with atrial fibrillation) Study.

BACKGROUND: In the acute phase of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF), the recurrence rate is high. Nonvitamin K antagonist oral anticoagulants may be appropriate for prevention of early recurrence because they have a much lower risk of hemorrhagic stroke than warfarin. METHODS: RELAXED (Recurrent Embolism Lessened by rivaroxaban, an Anti-Xa agent, of Early Dosing for acute ischemic stroke and transient ischemic attack with atrial fibrillation) study is an observational study designed to investigate the optimal timing to start administration of rivaroxaban for prevention of recurrence in NVAF patients in the acute phase of cardioembolic stroke (ClinicalTrials.gov: NCT02129920 and UMIN-clinical trials registry: UMIN000013932). It will evaluate the efficacy and safety of rivaroxaban with regard to infarct size, timing of initiation of rivaroxaban medication, and other patient characteristics. A total of 2000 consecutive patients with acute ischemic stroke in the territory of the middle cerebral artery and NVAF will be enrolled in 100 institutes throughout Japan, and they will receive rivaroxaban within 30 days of the index stroke for secondary prevention of stroke. The infarct size within 48 hours after stroke onset will be measured by diffusion-weighted magnetic resonance imaging. The primary efficacy endpoint is recurrent ischemic stroke, and the primary safety endpoint is major bleeding during the observational period of 3 months after stroke onset. The optimal timing to start treatment with rivaroxaban during the acute stage of ischemic stroke will be determined by analysis of the correlation between primary endpoints and the size of cerebral infarct. CONCLUSIONS: The RELAXED observational registry study will elucidate the optimal timing of the initiation of rivaroxaban in acute cardioembolic stroke associated with NVAF.

Differences in Clinical Characteristics between Patients with Transient Ischemic Attack Whose Symptoms Do and Do Not Persist on Arrival.

BACKGROUND: Symptoms of transient ischemic attack (TIA) persist on arrival and subsequently resolve in some patients admitted to hospitals early after onset. Differences in clinical characteristics between patients with acute TIA whose symptoms do and do not persist on arrival remain unclear. METHODS: We retrospectively extracted data of consecutive TIA patients with an onset-to-door time (ODT) of 24 hours or less and without a history of stroke from a multicenter TIA database. Clinical characteristics were compared between patients with and without persisting symptoms on arrival. RESULTS: Two hundred sixty-six patients (158 men, 68.0 ± 12.9 years) were included. Of the total number of patients, 105 (39.5%) had persisting symptoms with a mean National Institutes of Health Stroke Scale score of 2.4 (median, 1.0). Patients with persisting symptoms were more likely to have sensory disorder, ambulance-transported admission, long-duration TIA (≥60 minutes), and shorter ODT than those without. Multivariate analysis showed that sensory disorder (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.35-4.77), ambulance-transported admission (OR 1.80, 95% CI 1.00-3.28), and long-duration TIA (OR 3.96, 95% CI 2.12-7.71) were positively associated and that an ODT of more than 12 hours (OR .18, 95% CI .04-.63) was inversely associated with the presence ofpersisting symptoms. Patients with persisting symptoms were more likely to be examined by a stroke physician at first (69% versus 57%, P = .049) and then hospitalized in a stroke unit (59% versus 43%, P = .010). CONCLUSION: Clinical manifestations and management after admission might differ between patients with acute TIA whose symptoms do and do not persist on arrival.

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.

Factors associated with onset-to-door time in patients with transient ischemic attack admitted to stroke centers.

BACKGROUND AND PURPOSE: The aim of this study was to elucidate the factors associated with the time from symptom onset to arrival at a stroke center (onset-to-door time [ODT]) in patients with classically defined transient ischemic attack using data from a multicenter, retrospective study. METHODS: The subjects were patients with transient ischemic attack admitted to 13 stroke centers in Japan within 7 days of onset between 2008 and 2009. A total of 464 patients registered (292 men, 68.5±13.2 years old), and 421 of them (268 men, 68.8±13.1 years old) were included in the analyses. ODT was classified into the following 5 categories: <3 hours, 3 to 6 hours, 7 to 12 hours, 13 to 24 hours, and >24 hours. RESULTS: There were 233 patients (55.3%) who visited a stroke center within 3 hours of symptom onset. Multiple ordinal logistic regression analysis revealed that motor weakness, speech disturbance, and duration of symptoms >10 minutes were independently associated with a short ODT. Furthermore, a history of transient ischemic attack and hypertension and a referral from another medical facility were independently associated with a long ODT. Patients with a higher ABCD2 score were likely to arrive at a stroke center more quickly. CONCLUSIONS: We identified several factors that were positively and negatively associated with the ODT in patients with transient ischemic attack.

Incidence and predictors of ischemic stroke events during hospitalization in patients with transient ischemic attack.

BACKGROUND: The purpose of this study was to elucidate the incidence and predictors of ischemic stroke or recurrent transient ischemic attack (TIA) during acute hospitalization in patients with TIA. METHODS: We carried out a multicenter retrospective study to clarify the characteristics of in-patients with TIA. The subjects of this study were TIA patients admitted to 13 stroke hospitals within 7 days after onset between 2008 and 2009. TIA was defined as focal neurologic symptoms ascribable to a vascular etiology lasting less than 24 h. We investigated the incidence and predictors of ischemic events including ischemic stroke or recurrent TIA during hospitalization. RESULTS: A total of 464 patients with TIA (292 men, 69 ± 13 years) were registered. Of those, 400 (86.2%) were admitted within 24 h of TIA onset. The mean length of hospital stay was 13 days. During hospitalization, 8 patients had ischemic strokes and 26 had recurrent TIAs. The leading subtype of 8 ischemic strokes was small vessel disease (n = 3) followed by cardioembolism (n = 2). Multiple logistic regression analysis showed that hypertension (OR: 3.41; 95% CI: 1.23-12.3), MRI-diffusion-weighted image positivity (OR: 2.49; 95% CI: 1.15-5.25), and hemiparesis (OR: 2.30; 95% CI: 1.02-5.88) were independently associated with ischemic events during hospitalization. CONCLUSIONS: In this study, 1.7% of patients with TIA had ischemic stroke during acute hospitalization, and the most common subtype was small vessel disease. Subsequent ischemic stroke and recurrent TIA were associated with hypertension, positive DWI findings, and hemiparesis.

Features of patients with transient monocular blindness: a multicenter retrospective study in Japan.

BACKGROUND: Transient monocular blindness (TMB) is associated with a transient ischemic attack (TIA). The purpose of this study was to investigate the features of TMB in the Japanese population using data from a multicenter retrospective study of TIA. METHODS: The subjects were consecutive TIA patients admitted to 13 stroke centers within 7 days after symptom onset. We compared clinical characteristics of patients with TMB and those without TMB who had other symptoms of cerebral TIA. RESULTS: A total of 464 patients were registered between January 2008 and December 2009, and 444 patients (283 men, mean age: 68.5 years) were included in the analysis. Thirteen patients (2.9%) presented with TMB. Patients with TMB were less likely to arrive at the specialized stroke center quickly than those without TMB (P = .013). Stenotic lesions in the extracranial internal carotid artery were more common in patients with TMB (33.3% versus 9.1%, P = .022). CONCLUSIONS: TMB was not common in our TIA inpatients. This study suggests that patients with TMB should immediately undergo a diagnostic workup, including brain and vessel imaging, and cardiac evaluation, as is performed in patients with other cerebral TIA symptoms. A larger, prospective cohort is needed to confirm the risks and outcomes of patients with TMB in the Japanese population.

[Thrombolytic agents].

Thrombolytic agents positively resolve existing thrombi by accelerating the activity of plasmin, a key enzyme of the fibrinolytic pathway. The main drug in use is a plasminogen activator (PA) which degrades plasminogen to plasmin. PA is classified into urokinase-type (u-PA) and tissue-type (t-PA). Because t-PA more selectively activates plasmin onto the surface of thrombi, it induces less in terms of systemic hemorrhagic complications. Beside the main effects, some articles have reported that t-PA causes damage to blood brain barrier structures and has a level of neuron toxicity. With this, delayed administration of t-PA for acute ischemic stroke may accelerate ischemic damage of brain tissue. In circulating blood, plasmin itself is rapidly inactivated by a plasmin-inhibitor, so with this, intra-arterial administration of plasmin directly near thrombi site is currently under investigation.

Left Atrial Appendage Closure with the Watchman FLX System in a Patient with Hypertrophic Cardiomyopathy on Dialysis for End-stage Renal Failure.

Patients with hypertrophic cardiomyopathy (HCM) often have atrial fibrillation, and empiric anticoagulation is recommended in these patients, regardless of other risk factors. However, anticoagulation is not recommended for patients who require hemodialysis (HD) because of the high bleeding risk. We herein report a case of left atrial appendage closure (LAAC) using the Watchman FLX system for a dilated phase HCM patient complicated by persistent atrial fibrillation and requiring HD. LAAC with the Watchman FLX system may be an alternative to antithrombotic medications in patients with dilated HCM complicated by atrial fibrillation and requiring HD.

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.

Prognostic significance of smoking in patients with acute ischemic stroke within 3 months of onset.

BACKGROUND: Various factors that have been implicated in recovery after the acute phase of stroke have not been well evaluated. METHODS: To identify prognostic factors affecting outcomes at 90 days after stroke from the viewpoint of recovery patterns, we enrolled 660 patients from the Edaravone and Argatroban Stroke Therapy for Acute Ischemic Stroke study database. Fourteen groups of patients were identified based on an analysis of their recovery patterns according to changes in their National Institutes of Health Stroke Scale scores during the first 21 days. These groups were then divided into 2 groups: favorable recovery trend (patterns 1-3; n = 486) and poor recovery trend (patterns 4-14; n = 174). Patterns with >80% of the patients experiencing a favorable outcome (National Institutes of Health Stroke Scale score of ≤ 4 at 90 days) were defined as the favorable recovery trend group, whereas patterns that included ≤ 80% favorable outcomes were defined as the poor recovery trend group. RESULTS: Using the poor recovery trend group, logistic regression analysis found that after controlling for covariates, lower scores at admission, fewer ischemic lesions, and nonsmoking were significant prognostic factors for a favorable outcome at 90 days. CONCLUSIONS: Based on a detailed analysis of the relationship between recovery patterns after stroke and clinical outcomes in the chronic stage of stroke, smoking cessation may improve the prognosis of patients after stroke.

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.