Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial.

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03-1.36), that of a 10 mmHg SBP increase was 1.14 (1.03-1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00-1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

Clinical impact of body mass index on outcomes of ischemic and hemorrhagic strokes.

BACKGROUND AND AIM: To investigate the prognostic implication of body mass index (BMI) on clinical outcomes after acute ischemic and hemorrhagic stroke. METHODS: The subjects of the study included adult patients with available baseline body weight and height data who had suffered an acute stroke and were registered in the Japan Stroke Data Bank-a hospital-based, multicenter stroke registration database-between January 2006 and December 2020. The outcome measures included unfavorable outcomes defined as a modified Rankin Scale (mRS) score of 5-6 and favorable outcomes (mRS 0-2) at discharge, and in-hospital mortality. Mixed effects logistic regression analysis was conducted to determine the relationship between BMI categories (underweight, normal weight, overweight, class I obesity, class II obesity; <18.5, 18.5-23.0, 23.0-25.0, 25-30, ⩾30 kg/m2) and the outcomes, after adjustment for covariates. RESULTS: A total of 56,230 patients were assigned to one of the following groups: ischemic stroke (IS, n = 43,668), intracerebral hemorrhage (ICH, n = 9741), and subarachnoid hemorrhage (SAH, n = 2821). In the IS group, being underweight was associated with an increased likelihood of unfavorable outcomes (odds ratio, 1.47 (95% confidence interval (CI):1.31-1.65)) and in-hospital mortality (1.55 (1.31-1.83)) compared to outcomes in those with normal weight. Being overweight was associated with an increased likelihood of favorable outcomes (1.09 (1.01-1.18)). Similar associations were observed between underweight and these outcomes in specific IS subtypes (cardioembolic stroke, large artery stroke, and small-vessel occlusion). Patients with a BMI ⩾30.0 kg/m2 was associated with an increased likelihood of unfavorable outcomes (1.44 (1.01-2.17)) and in-hospital mortality (2.42 (1.26-4.65)) in large artery stroke. In patients with ICH, but not those with SAH, being underweight was associated with an increased likelihood of unfavorable outcomes (1.41 (1.01-1.99)). CONCLUSIONS: BMI substantially impacts functional outcomes following IS and ICH. Lower BMI consistently affected post-stroke disability and mortality, while higher BMI values similarly affected these outcomes after large artery stroke.

Higher Frequency of Premature Atrial Contractions Correlates With Atrial Fibrillation Detection after Cryptogenic Stroke.

BACKGROUND: Covert atrial fibrillation (AF) is a major cause of cryptogenic stroke. This study investigated whether a dose-dependent relationship exists between the frequency of premature atrial contractions (PACs) and AF detection in patients with cryptogenic stroke using an insertable cardiac monitor (ICM). METHODS: We enrolled consecutive patients with cryptogenic stroke who underwent ICM implantation between October 2016 and September 2020 at 8 stroke centers in Japan. Patients were divided into 3 groups according to the PAC count on 24-hour Holter ECG: ≤200 (group L), >200 to ≤500 (group M), and >500 (group H). We defined a high AF burden as above the median of the cumulative duration of AF episodes during the entire monitoring period. We evaluated the association of the frequency of PACs with AF detection using log-rank trend test and Cox proportional hazard model and with high AF burden using logistic regression model, adjusting for age, sex, CHADS2 score. RESULTS: Of 417 patients, we analyzed 381 patients with Holter ECG and ICM data. The median age was 70 (interquartile range, 59.5-76.5), 246 patients (65%) were males, and the median duration of ICM recording was 605 days (interquartile range, 397-827 days). The rate of new AF detected by ICM was higher in groups with more frequent PAC (15.5%/y in group L [n=277] versus 44.0%/y in group M [n=42] versus 71.4%/y in group H [n=62]; log-rank trend P<0.01). Compared with group L, the adjusted hazard ratios for AF detection in groups M and H were 2.11 (95% CI, 1.24-3.58) and 3.23 (95% CI, 2.07-5.04), respectively, and the adjusted odds ratio for high AF burden in groups M and H were 2.57 (95% CI, 1.14-5.74) and 4.25 (2.14-8.47), respectively. CONCLUSIONS: The frequency of PACs was dose-dependently associated with AF detection in patients with cryptogenic stroke.

Presenting Symptoms and Diffusion-Weighted MRI Positivity by Time After Transient Neurologic Events: A Pooled Analysis of 3 Cohort Studies

BACKGROUND AND OBJECTIVE: The association between focal vs nonfocal presenting symptom and diffusion-weighted imaging (DWI) positivity in relation to onset-to-imaging time in patients with transient neurologic events remains unclear. We hypothesize that episodes consisting of focal symptoms would have proportionally higher DWI-positive imaging at later onset-to-imaging times. METHODS: Patients with transient neurologic symptoms and a normal neurologic examination who had DWI in the combined data set of 3 cohort studies were included. We used logistic regression models to evaluate the association between each type of presenting symptom (motor weakness, speech impairment, sensory symptoms, vision loss, diplopia, gait instability, dizziness, headache, presyncope, and amnesia) and DWI positivity after adjusting for clinical variables (age, sex, history of stroke, dyslipidemia, coronary artery disease, atrial fibrillation, symptoms duration [<10, 10-59, ≥60 minutes, or unclear], and study source). We stratified the results by onset-to-imaging time categories (<6 hours, 6-23 hours, and ≥24 hours). RESULTS: Of the total 2,411 patients (1,345 male, median age 68 years), DWI-positive lesions were detected in 598 patients (24.8%). The prevalence of DWI positivity was highest in those with motor weakness (34.7%), followed by speech impairment (33.5%). In a multivariable analysis, the presence of motor weakness, speech impairment, and sensory symptoms was associated with DWI positivity, while vision loss and headache were associated with lower odds of DWI positivity, but nevertheless had 13.6% and 15.3% frequency of DWI positive. The odds of being DWI positive varied by onset-to-imaging time categories for motor weakness, with greater odds of being DWI positive at later imaging time (<6 hours: odds ratio [OR] 1.25, 95% confidence interval [CI] 0.84-1.87; 6-23 hours: OR 2.24, 95% CI 1.47-3.42; and ≥24 hours: OR 2.42, 95% CI 1.74-3.36; interaction p = 0.033). Associations of other symptoms with DWI positivity did not vary significantly by time categories. DISCUSSION: We found that onset-to-imaging time influences the relationship between motor weakness and DWI positivity in patients with transient neurologic events. Compared with motor, speech, and sensory symptoms, visual or nonfocal symptoms carry a lower but still a substantive association with DWI positivity.

Atrial Fibrillation Detection and Ischemic Stroke Recurrence in Cryptogenic Stroke: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Atrial fibrillation (AF) is known to be a strong risk factor for stroke. However, the risk of stroke recurrence in patients with cryptogenic stroke with AF detected after stroke by an insertable cardiac monitor (ICM) is not well known. We sought to evaluate the risk of ischemic stroke recurrence in patients with cryptogenic stroke with and without ICM-detected AF. METHODS AND RESULTS: We retrospectively reviewed patients with cryptogenic stroke who underwent ICM implantation at 8 stroke centers in Japan. Cox regression models were developed using landmark analysis and time-dependent analysis. We set the target sample size at 300 patients based on our estimate of the annualized incidence of ischemic stroke recurrence to be 3% in patients without AF detection and 9% in patients with AF detection. Of the 370 patients, 121 were found to have AF, and 110 received anticoagulation therapy after AF detection. The incidence of ischemic stroke recurrence was 4.0% in 249 patients without AF detection and 5.8% in 121 patients with AF detection (P=0.45). In a landmark analysis, the risk of ischemic stroke recurrence was not higher in patients with AF detected ≤90 days than in those without (hazard ratio, 1.47 [95% CI, 0.41-5.28]). In a time-dependent analysis, the risk of ischemic stroke recurrence did not increase after AF detection (hazard ratio, 1.77 [95% CI, 0.70-4.47]). CONCLUSIONS: The risk of ischemic stroke recurrence in patients with cryptogenic stroke with ICM-detected AF, 90% of whom were subsequently anticoagulated, was not higher than in those without ICM-detected AF.

Improvement of Functional Outcomes in Patients with Stroke who Received Alteplase for Over 15 Years: Japan Stroke Data Bank.

AIM: The nationwide verification of intravenous thrombolysis (IVT) was rarely performed after the extension of the therapeutic time window of alteplase or after the expansion of mechanical thrombectomy (MT). We aimed to examine the long-term change in accurate real-world outcomes of IVT in patients with acute ischemic stroke (AIS) using the Japan Stroke Databank, a representative Japan-wide stroke database. METHODS: We extracted all patients with AIS who received IVT with alteplase between October 11, 2005, the approval date for alteplase use for AIS in Japan, and December 31, 2020. Patients were categorized into three groups using two critical dates in Japan as cutoffs: the official extension date of the therapeutic time window for IVT to within 4.5 h of symptom onset and the publication date of the revised guideline, where the evidence level of MT was heightened. We assessed the yearly trend of IVT implementation rates and the secular changes and three-group changes in clinical outcomes at discharge. RESULTS: Of 124,382 patients with AIS, 9,569 (7.7%) received IVT (females, 41%; median age, 75 years). The IVT implementation rate has generally increased over time and plateaued in recent years. The proportion of favorable outcomes (modified Rankin Scale score of 0-2) increased yearly over 15 years. The results of the changes in the outcomes of the three groups were similar to those of the annual changes. CONCLUSIONS: We revealed that IVT implementation rates in patients with AIS increased, and the functional outcome in these patients improved over 15 years. Therefore, the Japanese IVT dissemination strategy is considered appropriate and effective.

Mode of Imaging Study and Endovascular Therapy for a Large Ischemic Core: Insights From the RESCUE-Japan LIMIT.

BACKGROUND AND PURPOSE: Differences in measurement of the extent of acute ischemic stroke using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) by non-contrast computed tomography (CT-ASPECTS stratum) and diffusion-weighted imaging (DWI-ASPECTS stratum) may impact the efficacy of endovascular therapy (EVT) in patients with a large ischemic core. METHODS: The RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan-Large IscheMIc core Trial) was a multicenter, open-label, randomized clinical trial that evaluated the efficacy and safety of EVT in patients with ASPECTS of 3-5. CT-ASPECTS was prioritized when both CT-ASPECTS and DWI-ASPECTS were measured. The effects of EVT on the modified Rankin Scale (mRS) score at 90 days were assessed separately for each stratum. RESULTS: Among 183 patients, 112 (EVT group, 53; No-EVT group, 59) were in the CT-ASPECTS stratum and 71 (EVT group, 40; No-EVT group, 31) in the DWI-ASPECTS stratum. The common odds ratio (OR) (95% confidence interval) of the EVT group for one scale shift of the mRS score toward 0 was 1.29 (0.65-2.54) compared to the No-EVT group in CT-ASPECTS stratum, and 6.15 (2.46-16.3) in DWI-ASPECTS stratum with significant interaction between treatment assignment and mode of imaging study (P=0.002). There were significant interactions in the improvement of the National Institutes of Health Stroke Scale score at 48 hours (CT-ASPECTS stratum: OR, 1.95; DWIASPECTS stratum: OR, 14.5; interaction P=0.035) and mortality at 90 days (CT-ASPECTS stratum: OR, 2.07; DWI-ASPECTS stratum: OR, 0.23; interaction P=0.008). CONCLUSION: Patients with ASPECTS of 3-5 on MRI benefitted more from EVT than those with ASPECTS of 3-5 on CT.

Characteristics and outcomes of unknown onset stroke: The Japan Stroke Data Bank.

BACKGROUND: Clinical outcomes of unknown onset stroke (UOS) are influenced by the enlargement of the therapeutic time window for reperfusion therapy. This study aimed to investigate and describe the characteristics and clinical outcomes of patients with UOS. METHODS: Patients with acute ischemic stroke (AIS) who were admitted within 24 h of their last known well time, from January 2017 to December 2020, were included. Data were obtained from a long-lasting nationwide hospital-based multicenter prospective registry: the Japan Stroke Data Bank. The co-primary outcomes were the National Institutes of Stroke Scale (NIHSS) scores on admission and unfavorable outcomes at discharge, corresponding to modified Rankin Scale (mRS) scores of 3-6. RESULTS: Overall, 26,976 patients with AIS were investigated. Patients with UOS (N = 5783, 78 ± 12 years of age) were older than patients with known onset stroke (KOS) (N = 21,193, 75 ± 13 years of age). Age, female sex, higher premorbid mRS scores, atrial fibrillation, and congestive heart failure were associated with UOS in multivariate analysis. UOS was associated with higher NIHSS scores (median = 8 [interquartile range [IQR]: 3-19] vs. 4 [1-10], adjusted incidence rate ratio = 1.37 [95% CI: 1.35-1.38]) and unfavorable outcomes (52.1 vs. 33.6%, adjusted odds ratio = 1.27 [1.14-1.40]). Intergroup differences in unfavorable outcomes were attenuated among females (1.12 [0.95-1.32] vs. males 1.38 [1.21-1.56], P = 0.040) and in the subgroup that received reperfusion therapy (1.10 [0.92-1.33] vs. those who did not receive therapy 1.23 [1.08-1.39], P = 0.012). CONCLUSIONS: UOS was associated with unfavorable outcomes but to a lesser degree among females and patients receiving reperfusion therapy.

Left atrial appendage flow velocity predicts occult atrial fibrillation in cryptogenic stroke: a CRYPTON-ICM registry.

BACKGROUND: An insertable cardiac monitor (ICM) and transesophageal echocardiography (TEE) are useful for investigating potential embolic sources in cryptogenic stroke, of which atrial fibrillation (AF) is a critical risk factor for stroke recurrence. The association of left atrial appendage flow velocity (LAA-FV) on TEE with ICM-detected AF is yet to be elucidated. METHODS: CRYPTON-ICM (CRYPTOgenic stroke evaluation in Nippon using ICM) is a multicenter registry of cryptogenic stroke with ICM implantation, and patients whose LAA-FV was evaluated on TEE were enrolled. The primary outcome was the detection of AF (> 2 min) on ICM. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off of LAA-FV, and factors associated with ICM-detected AF were assessed. RESULTS: A total of 307 patients (age 66.6 ± 12.3 years; 199 males) with median follow-up of 440 (interquartile range 169-726) days were enrolled; AF was detected in 101 patients. The lower-tertile LAA-FV group had older age, more history of congestive heart failure, and higher levels of B-type natriuretic peptide (BNP) or N-terminal proBNP (all P < 0.05). On ROC analysis, LAA-FV < 37.5 cm/s predicted ICM-detected AF with sensitivity of 26.7% and specificity of 92.2%. After adjustment for covariates, the lower tertile of LAA-FV (hazard ratio [HR], 1.753 [1.017-3.021], P = 0.043) and LAA-FV < 37.5 cm/s (HR 1.987 [1.240-3.184], P = 0.004) predicted ICM-detected AF. CONCLUSIONS: LAA-FV < 37.5 cm/s predicts AF. TEE is useful not only to evaluate potential embolic sources, but also for long-term detection of AF on ICM by measuring LAA-FV in cryptogenic stroke. http://www.umin.ac.jp/ctr/ (UMIN000044366).

Tmax Mismatch Ratio to Identify Intracranial Atherosclerotic Stenosis-Related Large-Vessel Occlusion Before Endovascular Therapy.

Background We aimed to clarify which time-to-maximum of the tissue residue function (Tmax) mismatch ratio is useful in predicting anterior intracranial atherosclerotic stenosis (ICAS)-related large-vessel occlusion (LVO) before endovascular therapy. Methods and Results Patients with ischemic stroke who underwent perfusion-weighted imaging before endovascular therapy for anterior intracranial LVO were divided into those with ICAS-related LVO and those with embolic LVO. Tmax ratios of >10 s/>8 s, >10 s/>6 s, >10 s/>4 s, >8 s/>6 s, >8 s/>4 s, and >6 s/>4 s were considered Tmax mismatch ratios. Binominal logistic regression was used to identify ICAS-related LVO, and the adjusted odds ratio (aOR) and 95% CI for each Tmax mismatch ratio increase of 0.1 were calculated. A similar analysis was performed for ICAS-related LVO with and without embolic sources, using embolic LVO as the reference. Of 213 patients (90 women [42.0%]; median age, 79 years), 39 (18.3%) had ICAS-related LVO. The aOR (95% CI) per 0.1 increase in Tmax mismatch ratio in ICAS-related LVO with embolic LVO as reference was lowest with Tmax mismatch ratio >10 s/>6 s (0.56 [0.43-0.73]). Multinomial logistic regression analysis also showed the lowest aOR (95% CI) per 0.1 increase in Tmax mismatch ratio with Tmax >10 s/>6 s (ICAS-related LVO without embolic source: 0.60 [0.42-0.85]; ICAS-related LVO with embolic source: 0.55 [0.38-0.79]). Conclusions A Tmax mismatch ratio of >10 s/>6 s was the optimal predictor of ICAS-related LVO compared with other Tmax profiles, with or without an embolic source before endovascular therapy. Registration clinicaltrials.gov. Identifier NCT02251665.

P-wave terminal force in lead V1 and atrial fibrillation burden in cryptogenic stroke with implantable loop recorders.

Implantable loop recorders (ILRs) are useful for the detection of atrial fibrillation (AF) in patients with cryptogenic stroke (CS). P-wave terminal force in lead V1 (PTFV1) is associated with AF detection; however, data on the association between PTFV1 and AF detection using ILRs in patients with CS are limited. Consecutive patients with CS with implanted ILRs from September 2016 to September 2020 at eight hospitals in Japan were studied. PTFV1 was calculated by 12-lead ECG before ILRs implantation. An abnormal PTFV1 was defined as ≥ 4.0 mV × ms. The AF burden was calculated as a proportion based on the duration of AF to the total monitoring period. The outcomes included AF detection and large AF burden, which was defined as ≥ 0.5% of the overall AF burden. Of 321 patients (median age, 71 years; male, 62%), AF was detected in 106 patients (33%) during the median follow-up period of 636 days (interquartile range [IQR], 436-860 days). The median time from ILRs implantation to AF detection was 73 days (IQR, 14-299 days). An abnormal PTFV1 was independently associated with AF detection (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.00-2.90). An abnormal PTFV1 was also independently associated with a large AF burden (adjusted odds ratio, 4.70; 95% CI, 2.50-8.80). In patients with CS with implanted ILRs, an abnormal PTFV1 is associated with both AF detection and a large AF burden.Clinical Trial Registration Information: UMIN Clinical Trials Registry 000044366.

Stent Retriever or Aspiration Catheter Alone vs Their Combination as the First-Line Thrombectomy in Acute Stroke.

BACKGROUND: The single-device simplicity for mechanical thrombectomy (MT) is now challenged by the complementary efficacy of dual-device first-line with a stent retriever and an aspiration catheter. OBJECTIVE: To compare the outcomes after MT initiated with a single device vs dual devices in acute anterior circulation large vessel occlusion. METHODS: Patients who underwent MT for acute internal carotid artery (ICA) or M1 occlusion between 2015 and 2020 were retrospectively analyzed. We divided patients into 2 groups: single-device first-line, defined as patients who underwent first-device pass with either a stent retriever or aspiration catheter, and dual-device first-line, defined as first-device pass with both devices. RESULTS: One hundred forty-one patients were in the single-device group, and 119 were in the dual-device group. In the dual-device group, coiling or kinking of the extracranial ICA was more frequent ( P = .07) and the guide catheters were less frequently navigated to the ICA ( P < .001). 37% of the single-device group was converted to dual-device use. The proportions of mTICI ≥ 2c after the first pass were similar (33% vs 32%. adjusted odds ratio 0.91, 95% CI 0.51-1.62). An mRS score of 0 to 2 at 3 months was achieved similarly (53% vs 48%, P = .46). The total cost for thrombectomy devices was lower in the single-device group ( P < .001). CONCLUSION: The proportions of first-pass mTICI ≥ 2c were not different between the 2 groups with similar functional outcomes, although the dual-device group more likely to have unfavorable vascular conditions.

Detrimental effect of anemia after mechanical thrombectomy on functional outcome in patients with ischemic stroke.

Background: Anemia can occur due to an aspiration maneuver of blood with thrombi during mechanical thrombectomy (MT) for stroke. However, the association between postoperative anemia and stroke outcomes is unknown. Methods: In a registry-based hospital cohort, consecutive patients with acute ischemic stroke who underwent MT were retrospectively recruited. Patients were divided into the following three groups according to their hemoglobin (Hb) concentrations within 24 h after MT; no anemia (Hb concentrations ≥13 g/dL for men and ≥ 12 g/dL for women), mild anemia (Hb concentrations of 11-13 g/dL and 10-12 g/dL, respectively), and moderate-to-severe anemia (Hb concentrations <11 g/dL and < 10 g/dL, respectively). A 3-month modified Rankin Scale score of 0-2 indicated a favorable outcome. Results: Of 470 patients, 166 were classified into the no anemia group, 168 into the mild anemia group, and 136 into the moderate-to-severe anemia group. Patients in the moderate-to-severe anemia group were older and more commonly had congestive heart failure than those in the other groups. Patients in the moderate-to-severe anemia group also had more device passes than those in the other groups (p < 0.001). However, no difference was observed in the rate of final extended thrombolysis in cerebral infarction ≥2b reperfusion or intracranial hemorrhage among the groups. A favorable outcome was less frequently achieved in the moderate-to-severe anemia group than in the no anemia group (adjusted odds ratio, 0.46; 95% confidence interval, 0.26-0.81) independent of the baseline Hb concentration. A restricted cubic spline model with three knots showed that the adjusted odds ratio for a favorable outcome was lower in patients with lower Hb concentrations within 24 h after MT. Conclusion: Moderate-to-severe anemia within 24 h after MT is independently associated with a reduced likelihood of a favorable outcome. Clinical trial registration: https://www.clinicaltrials.gov, NCT02251665.

[Cerebral venous sinus thrombosis presenting transient ischemic attack after recovery from COVID-19 with Graves' disease and IgG4-related ophthalmic disease: a case report].

A 57-year-old man presented with headache, transient right upper extremity weakness and numbness one month after recovery from coronavirus disease 2019 (COVID-19). His medical history included Graves' disease and IgG4-related ophthalmic disease. He had been administered prednisolone. His weakness and numbness were transient and not present on admission. Contrast-enhanced CT and MRI of the head showed thrombi in the superior sagittal sinus, right transverse sinus, sigmoid sinus, and the right internal jugular vein. Digital subtraction angiography showed occlusion at the same sites and mild perfusion delay in the left frontoparietal lobe. We diagnosed the patient with cerebral venous sinus thrombosis and treated him with anticoagulation. The thrombi partially regressed three months later, and perfusion delay became less noticeable. Cerebral venous sinus thrombosis is an important complication of COVID-19. Patients with predisposing factors, including Graves' disease and IgG4-related ophthalmic disease, may be at increased risk of developing cerebral venous sinus thrombosis even after recovery from COVID-19.

Late-onset cerebral embolism after transcatheter aortic valve implantation under direct oral anticoagulant therapy.

Ischemic stroke is a devastating complication of transcatheter aortic valve implantation (TAVI), mainly occurring in the early postoperative period. The risk of a transplanted heart valve (THV) thrombosis causing stroke may be underestimated in the late postoperative phase. We describe the case of a 92-year-old woman with delayed valve thrombosis causing stroke after TAVI, who developed recurrent strokes eight months after TAVI for severe aortic valve stenosis. Transesophageal echocardiography and cardiac computed tomography revealed a string-like thrombus attached to the implanted valve. With the administration of warfarin, the clot regressed, and the patient was discharged home without recurrence of stroke. Our case demonstrates the importance of THV thrombosis as an embolic source of stroke even in the late postoperative phase and provides a discussion on optimal antithrombotic therapy after TAVI.

Internal Carotid Artery Tortuosity: Impact on Mechanical Thrombectomy.

BACKGROUND: Although tortuosity of the internal carotid artery (ICA) can pose a significant challenge when performing mechanical thrombectomy, few studies have examined the impact of ICA tortuosity on mechanical thrombectomy outcomes. METHODS: In a registry-based hospital cohort, consecutive patients with anterior circulation stroke in whom mechanical thrombectomy was attempted were divided into 2 groups: those with tortuosity in the extracranial or cavernous ICA (tortuous group) and those without (nontortuous group). The extracranial ICA tortuosity was defined as the presence of coiling or kinking. The cavernous ICA tortuosity was defined by the posterior deflection of the posterior genu or the shape resembling Simmons-type catheter. Outcomes included first pass effect (FPE; extended Thrombolysis in Cerebral Infarction score 2c/3 after first pass), favorable outcome (3-month modified Rankin Scale score of 0-2), and intracranial hemorrhage. RESULTS: Of 370 patients, 124 were in the tortuous group (extracranial ICA tortuosity, 35; cavernous ICA tortuosity, 70; tortuosity at both sites, 19). The tortuous group showed a higher proportion of women and atrial fibrillation than the nontortuous group. FPE was less frequently achieved in the tortuous group than the nontortuous group (21% versus 39%; adjusted odds ratio, 0.45 [95% CI, 0.26-0.77]). ICA tortuosity was independently associated with the longer time from puncture to extended Thrombolysis in Cerebral Infarction ≥2b reperfusion (ß=23.19 [95% CI, 13.44-32.94]). Favorable outcome was similar between groups (46% versus 48%; P=0.87). Frequencies of any intracranial hemorrhage (54% versus 42%; adjusted odds ratio, 1.61 [95% CI, 1.02-2.53]) and parenchymal hematoma (11% versus 6%; adjusted odds ratio, 2.41 [95% CI, 1.04-5.58]) were higher in the tortuous group. In the tortuous group, the FPE rate was similar in patients who underwent combined stent retriever and contact aspiration thrombectomy and in those who underwent either procedure alone (22% versus 19%; P=0.80). However, in the nontortuous group, the FPE rate was significantly higher in patients who underwent combined stent retriever and contact aspiration (52% versus 35%; P=0.02). CONCLUSIONS: ICA tortuosity was independently associated with reduced likelihood of FPE and increased risk of postmechanical thrombectomy intracranial hemorrhage. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02251665.

Early initiation of rivaroxaban after reperfusion therapy for stroke patients with nonvalvular atrial fibrillation.

BACKGROUND: The optimal timing of initiating oral anticoagulants after reperfusion therapy for ischemic stroke is unknown. Factors related to early initiation of rivaroxaban and differences in clinical outcomes of stroke patients with nonvalvular atrial fibrillation (NVAF) who underwent reperfusion therapy was investigated. METHODS: From data of 1,333 NVAF patients with ischemic stroke or transient ischemic attack (TIA) in a prospective multicenter study, patients who started rivaroxaban after intravenous thrombolysis and/or mechanical thrombectomy were included. The clinical outcomes included the composite of ischemic events (recurrent ischemic stroke, TIA, or systemic embolism) and major bleeding at 3 months. RESULTS: Among the 424 patients, the median time from index stroke to starting rivaroxaban was 3.2 days. On multivariable logistic regression analysis, infarct size (odds ratio [OR], 0.99; 95%CI, 0.99-1.00) was inversely and successful reperfusion (OR, 2.13; 95%CI, 1.24-3.72) was positively associated with initiation of rivaroxaban within 72 hours. 205 patients were assigned to the early group (< 72 hours) and 219 patients (≥ 72 hours) to the late group. Multivariable Cox regression models showed comparable hazard ratios between the two groups at 3 months for ischemic events (hazard ratio [HR], 0.18; 95%CI, 0.03-1.32) and major bleeding (HR, 1.80; 95%CI, 0.24-13.54). CONCLUSIONS: Infarct size and results of reperfusion therapy were associated with the timing of starting rivaroxaban. There were no significant differences in the rates of ischemic events and major bleeding between patients after reperfusion therapy who started rivaroxaban < 72 hours and ≥ 72 hours after the index stroke. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT02129920; URL: https://www.clinicaltrials.gov.

Etiology and Outcome of Ischemic Stroke in Patients With Renal Impairment Including Chronic Kidney Disease: Japan Stroke Data Bank.

BACKGROUND AND OBJECTIVES: Chronic kidney disease is a worldwide public health problem that is recognized as an established risk factor for stroke. It remains unclear whether its distribution and clinical impact are consistent across ischemic stroke subtypes in patients with renal impairment. We examined whether renal impairment was associated with the proportion of each stroke subtype vs ischemic stroke overall and with functional outcomes after each stroke subtype. METHODS: Study participants were 10,392 adult patients with an acute stroke from the register of the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between October 2016 and December 2019, whose baseline serum creatinine levels or a dipstick proteinuria result were available. All ischemic strokes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Unfavorable functional outcome was defined as modified Rankin Scale (mRS) score 3-6 at discharge. Mixed effect logistic regression was used to determine the relationship between the outcomes and the estimated glomerular filtration rate (eGFR), eGFR strata (<45, 45-59, ≥60 mL/min/1.73 m2), or dipstick proteinuria ≥1 adjusted for covariates. RESULTS: Overall, 2,419 (23%) patients had eGFR 45-59 mL/min/1.73 m2 and 1,976 (19%) had eGFR <45 mL/min/1.73 m2, including 185 patients (1.8%) receiving hemodialysis. Both eGFR 45-59 and eGFR <45 mL/min/1.73 m2 were associated with a higher proportion of cardioembolic stroke (odds ratio [OR], 1.21 [95% CI, 1.05-1.39] and 1.55 [1.34-1.79], respectively) and a lower proportion of small vessel occlusion (0.79 [0.69-0.90] and 0.68 [0.59-0.79], respectively). A similar association with the proportion of these 2 subtypes was proven in the analyses using decreased eGFR as continuous values. Both eGFR <45 mL/min/1.73 m2 and proteinuria were associated with unfavorable functional outcomes in patients with cardioembolic stroke (OR, 1.30 [95% CI, 1.01-1.69] and 3.18 [2.03-4.98], respectively) and small vessel occlusion (OR, 1.44 [1.01-2.07] and 2.08 [1.08-3.98], respectively). DISCUSSION: Renal impairment contributes to the different distributions and clinical effects across specific stroke subtypes, particularly evident in cardioembolic stroke and small vessel occlusion. This possibly indicates shared mechanisms of susceptibility and potentially enhancing pathways.

[A case of recurrent cerebral embolism associated with Lambl's excrescence].

A 75-year-old female had a history of prior ischemic stroke with aphasia and right hemiplegia. Magnetic resonance angiography showed left internal carotid artery occlusion. She was successfully treated with intravenous recombinant tissue plasminogen activator (IV t-PA) and underwent endovascular thrombectomy (EVT). She was diagnosed with cardioembolic stroke due to the presence of atrial fibrillation and mitral valve stenosis, and warfarin was administered. However, she experienced large vessel occlusion twice within 2 years. Upon further analysis, transesophageal echocardiography revealed a mobile hyperechoic structure on the aortic valve, which was assumed to be an embolic source. Thus, we decided to perform mitral and aortic valve replacement. The excised aortic valve structure was suggested to be an example of Lambl's excrescence, histopathologically. After surgery, the patient had no recurrence for 3 years. Several cases of ischemic stroke associated with Lambl's excrescence have been reported, but definitive guidelines for managing patients with Lambl's excrescence do not currently exist. Surgical intervention for Lambl's excrescence with recurrent ischemic events may be important for preventing further recurrence.

Evaluation of Workflow Delays in Stroke Reperfusion Therapy: A Comparison between the Year-Long Pre-COVID-19 Period and the with-COVID-19 Period.

AIM: We evaluated the delay in stroke reperfusion therapy between the pre-coronavirus disease 2019 (COVID-19) period and the with-COVID-19 period, and compared this delay between each phase of the with-COVID-19 period. METHODS: Patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis and/or mechanical thrombectomy were selected from our single-center prospective registry. The time to perform reperfusion therapy were compared between patients admitted from March 2019 to February 2020 (pre-COVID-19 group) and those from March 2020 to February 2021 (with-COVID-19 group). Patients in the with-COVID-19 group were further divided into three 4-month-long subgroups (first-phase: March to June 2020; second-phase: July to October 2020; third-phase: November 2020 to February 2021), and the time delay of reperfusion therapy were compared between these subgroups. RESULTS: Of 1,260 patients with AIS hospitalized in the study period, 265 patients were examined. Compared with the pre-COVID-19 group (133 patients; median age, 79 years), the with-COVID-19 group (132 patients; median age, 79 years) had a longer median door-to-imaging time (25 min vs. 27 min, P=0.04), and a longer door-to-groin puncture time (65 min vs. 72 min, P=0.02). In the three 4-month-long subgroups, the median door-to-needle time (49 min, 43 min, and 38 min, respectively; P=0.04) and door-to-groin puncture time (83 min, 70 min, and 61 min, P＜0.01, respectively) decreased significantly during the with-COVID-19 period. CONCLUSIONS: The delay in reperfusion therapy increased during the with-COVID-19 period compared with the pre-COVID-19 period. However, the door-to-needle time and door-to-groin puncture time decreased as time elapsed during the with-COVID-19 period. CLINICALTRIALS: gov Identifier: NCT02251665.