Percutaneous Left Atrial Appendage Occlusion Yields Favorable Neurological Outcomes in Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. METHODS: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment. Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. RESULTS: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively. Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). CONCLUSIONS: Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Effects of dabigatran and rivaroxaban on stroke severity according to the results of routine coagulation tests.

INTRODUCTION: Prior use of direct oral anticoagulants has been associated with reduced stroke severity in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the impact of prothrombin time (PT) and activated partial thromboplastin time (aPTT) on stroke severity in patients who were receiving dabigatran or rivaroxaban at the time of stroke onset. MATERIALS AND METHODS: We enrolled 107 patients with NVAF who developed acute ischemic stroke while on dabigatran or rivaroxaban and presented within 24 hours to nine hospitals between January 2014 and December 2018. The results of PT and aPTT assays were obtained within 24 hours of stroke onset in all patients. We analyzed PT and aPTT in relation to stroke severity and ischemic lesion volume using correlation and multivariable regression analyses. RESULTS: Of the 107 patients included, 46 (43.0%) were on dabigatran and 61 (57.0%) were on rivaroxaban. In patients with prior dabigatran use, while aPTT was inversely correlated with admission National Institutes of Health Stroke Scale (NIHSS) score (r = -0.369, p = 0.012) and ischemic lesion volume (r = -0.480, p = 0.005), there was no correlation between PT and either of these variables. Multivariable analysis confirmed the existence of a significant independent inverse relationship between aPTT and NIHSS score at admission (B, -0.201; 95% confidence interval [CI], -0.370 to -0.032; p = 0.005) and between aPTT and ischemic lesion volume (B, -0.076; 95% CI, -0.130 to -0.023; p = 0.007). In patients with prior rivaroxaban use, neither PT nor aPTT was associated with admission NIHSS score or ischemic lesion volume in the correlation and multivariable analyses. CONCLUSIONS: In patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity.

Advanced Liver Fibrosis Predicts Unfavorable Long-Term Prognosis in First-Ever Ischemic Stroke or Transient Ischemic Attack.

INTRODUCTION: There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA). OBJECTIVE: We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA. METHODS: This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of >3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used. RESULTS: There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40-6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59-12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05-3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037). CONCLUSIONS: The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA.

Non-vitamin K oral anticoagulants as first-line regimen for acute ischemic stroke with non-valvular atrial fibrillation.

PURPOSE: There are various patterns in determining the choice of the first-line antithrombotic agent for acute stroke with non-valvular atrial fibrillation. We investigated the efficacy and safety of non-vitamin K oral anticoagulants as first-line antithrombotics for patients with acute stroke and non-valvular atrial fibrillation. MATERIALS AND METHODS: Patients with non-valvular atrial fibrillation and ischemic stroke or transient ischemic attack within 24 h from stroke onset were included. On the basis of the first regimen used and the regimen within 7 days after admission, the study population was divided into three groups: 1) antiplatelet switched to warfarin (A-W), 2) antiplatelet switched to NOAC (A-N), and 3) NOAC only (N only). We compared the occurrence of early neurologic deterioration, symptomatic intracranial hemorrhage, systemic bleeding, and poor functional outcome at 90 days. RESULTS: Of 314 included patients, 164, 53, and 97 were classified into the A-W, A-N, and N only groups, respectively. Early neurologic deterioration was most frequently observed in the A-W group (9.1%), followed by the A-N (5.7%) and N only (1.0%) groups (p = 0.017). Multivariable analysis adjusting for potential confounders demonstrated that the N only group was independently associated with a lower rate of early neurologic deterioration (odds ratio [OR] 0.104, 95% CI 0.013-0.831) or poor functional outcome at 90 days (OR 0.450, 95% CI 0.215-0.940) than the A-W group. However, the rate of symptomatic intracranial hemorrhage or any systemic bleeding event did not differ among the groups. CONCLUSION: Using non-vitamin K oral anticoagulants as the first-line regimen for acute ischemic stroke may help prevent early neurologic deterioration without increasing the bleeding risk.

Brachial-ankle pulse wave velocity for predicting functional outcomes in patients with cryptogenic stroke.

Even after extensive standard evaluation, the probable cause of stroke in some patients remains unclear; this condition is defined as cryptogenic stroke (CS). The prognosis of patients with CS is largely undetermined. We investigated whether higher brachial-ankle pulse wave velocities (baPWVs) can predict poor functional outcomes at 3 months after stroke onset in these patients. We investigated patients with CS with first-ever acute cerebral infarction who underwent baPWV measurements. The stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment classification. Poor functional outcomes were defined as modified Rankin Scale scores of >2 at 3 months after stroke onset. In total, 595 patients with CS were included; among them, 360 were men (60.5%). Their mean age was 65.0 ±â€¯12.4 years. One-hundred-eleven patients (18.7%) had poor functional outcomes. In the multivariable logistic regression analysis, the cutoff baPWV value based on the receiver-operating characteristic curve was >1968 cm/s, which was determined as a strong independent predictor (OR 3.159, 95% CI 1.487-6.715, p = 0.003). The OR of the cutoff value was higher in the patients with CS with initial National Institutes of Health Stroke Scale (NIHSS) scores of ≥5 (OR 4.252, 95% CI 1.596-11.324, p = 0.004); that in the patients with initial NIHSS scores of <5 was not significant (OR 1.671, 95% CI 0.620-4.505, p = 0.310). baPWV measurement during the acute stroke phase might be useful in identifying patients with CS at high risks of having a poor neurological prognosis.

Mechanical Thrombectomy in Subtypes of Basilar Artery Occlusion: Relationship to Recanalization Rate and Clinical Outcome.

Background Acute stroke because of basilar artery occlusion (BAO) represents 1% of all ischemic strokes. However, recanalization rates and treatment outcome for the different pathologic subtypes of BAO stroke are not fully understood. Purpose To compare the recanalization rate and clinical outcomes of mechanical thrombectomy in different subtypes of BAO. Materials and Methods Eighty-two patients (46 men and 36 women; mean age, 73 years; age range, 20-90 years; mean age in men, 70 years [age range, 20-90 years]; mean age in women, 75 years [age range; 61-90 years]) with acute BAO who underwent mechanical thrombectomy between March 2010 and December 2017 were retrospectively analyzed. Patients were classified into three groups: embolism without vertebral artery (VA) steno-occlusion (group 1), embolism from tandem VA steno-occlusion (group 2), and in situ atherosclerotic thrombosis (group 3). Clinical and angiographic characteristics, recanalization rate, procedure times, and clinical outcomes were compared between groups by using the Kruskal-Wallis, Pearson χ2, and Fisher exact tests. Results The incidence of BAO according to stroke mechanism were as follows: group 1, n = 34 (41%); group 2, n = 28 (34%), group 3, n = 20 (24%). Overall, successful recanalization (modified Thrombolysis in Cerebral Infarction grade 2b or 3) was achieved in 78% (64 of 82) and favorable outcome (90-day modified Rankin Scale score, 0-2) in 37% (30 of 82) of the patients. The procedure time was shorter in group 1 than in group 2 (49 vs 66 minutes, respectively; P = .01). Group 1 showed a higher successful recanalization rate than group 3 (29 of 34 [85%] vs 11 of 20 [55%], respectively; P = .01). Good clinical outcome rate was higher in group 1 than in group 3 (18 of 34 [53%] vs four of 20 [20%], respectively; P = .02). Conclusion The outcome of mechanical thrombectomy for basilar artery occlusion differs according to the pathologic mechanism of stroke; the best outcomes and recanalization rate occurred in patients with embolism without vertebral artery steno-occlusion. © RSNA, 2019 See also the editorial by Hetts in this issue.

Liver Fibrosis, Not Steatosis, Associates with Long-Term Outcomes in Ischaemic Stroke Patients.

BACKGROUND: To investigate whether there are differences in long-term all-cause and cardiovascular mortality according to the burden of liver fibrosis or steatosis in patients with ischaemic stroke or transient ischaemic attack (TIA). -Methods: Consecutive patients with acute ischaemic stroke or TIA who underwent transient elastography (TE) from January 2014 to December 2014 were considered eligible. The influence of liver fibrosis or steatosis, assessed via TE, on long-term outcomes was investigated using Cox proportional hazard models. RESULTS: Among 395 patients included in this study, there were 37 (9%) patients with significant fibrosis (> 8.0 kPa) and 164 (41.5%) patients with fatty liver (> 250 dB/m). During the follow-up period (median 2.7 years), all-cause and cardiovascular mortality occurred in 28 (7.1%) and 20 (5.1%) patients. On multivariate analyses, significant liver fibrosis was independently associated with increased risk of all-cause (hazard ratio [HR] 8.14, 95% CI 3.03-21.90, p < 0.001) and cardiovascular (HR 4.29, 95% CI 1.10-16.73, p = 0.036) mortality, whereas fatty liver was not (all p > 0.05). CONCLUSIONS: This study found that the burden of liver fibrosis but not that of steatosis, assessed via TE, was an independent predictor of all-cause and cardiovascular mortality during long-term follow-up in patients with ischaemic stroke.

Prediction of functional outcome using the novel asymmetric middle cerebral artery index in cryptogenic stroke patients.

BACKGROUND: Etiology is unknown in approximately one-quarter of stroke patients after evaluation, which is termed cryptogenic stroke (CS). The prognosis of CS patients is largely undetermined. We created a novel index from transcranial Doppler parameters including mean flow velocity (MV) and pulsatility index (PI) and investigated whether the calculation of asymmetry in the novel parameter can predict functional outcomes in CS patients. METHODS: We made the middle cerebral artery (MCA) index (%) as a novel parameter, which was calculated as 100 X (MCA MV + MCA PI X 10) / (MCA MV-MCA PI X 10). The MCA asymmetry index (%) was also calculated as 100 X (|Rt MCA index-Lt MCA index|) / (Rt MCA index + Lt MCA index) / 2. Poor functional outcomes were defined as modified Rankin Scale score (mRS) ≥3 at 3 months after stroke onset. RESULTS: A total of 377 CS patients were included. Among them, 52 (13.8%) patients had a poor outcome. The overall MCA asymmetry index was two-fold higher in CS patients with a poor outcome (10.26%) compared to those with a good outcome (5.41%, p = 0.002). In multivariable analysis, the overall MCA asymmetry index (OR, 1.054, 95% CI, 1.013-1.096, p = 0.009) and the cutoff value of the overall MCA asymmetry index >9 were associated with poor outcomes at 3 months (OR, 3.737, 95% CI, 1.530-9.128, p = 0.004). CONCLUSION: We demonstrated that the novel asymmetric MCA index can predict short-term functional outcomes in CS patients.

Stroke Severity in Patients on Non-Vitamin K Antagonist Oral Anticoagulants with a Standard or Insufficient Dose.

BACKGROUND: The stroke severity or functional outcomes could differ because the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) could be different according to the dose. We investigated whether there was any difference in the stroke outcomes in patients with non-valvular atrial fibrillation (NVAF) by their prior medication status, including standard-dosed versus under-dosed NOACs. MATERIALS AND METHODS: We enrolled 858 patients with acute ischaemic stroke with chronic NVAF admitted at six hospitals in Korea. We categorized their prior medication status as follows: (1) no anti-thrombotics (n = 219), (2) only anti-platelet (n = 347), (3) warfarin with a sub-therapeutic intensity (n = 185), (4) warfarin with a therapeutic intensity (n = 37), (5) under-dosed NOAC (n = 27) and (6) standard-dosed NOAC (n = 43). We compared the initial stroke severity between groups. RESULTS: Among the 858 patients, the patients on standard-dosed NOACs had the lowest initial National Institute of Health Stroke Scale (NIHSS) score, followed by those on warfarin with a therapeutic intensity and those on only anti-platelet (p < 0.05). Multivariate analysis demonstrated that the NIHSS score was significantly low in the patients on warfarin with a therapeutic intensity (B, -5.602; 95% confidence interval [CI], -8.636 to -2.568; p < 0.001) or those on standard-dosed NOACs (B, -3.588; 95% CI, -6.405 to -0.771; p = 0.013), while there was no difference in the NIHSS score between the patients not taking any anti-thrombotics and those on warfarin with a sub-therapeutic intensity or under-dosed NOACs. CONCLUSION: Use of warfarin with a therapeutic intensity or standard-dosed NOACs was associated with a relatively mild stroke in the patients with NVAF.

Impact of Non-vitamin K Antagonist Oral Anticoagulant Withdrawal on Stroke Outcomes.

Introduction: Discontinuation of oral anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) may induce a hypercoagulable state, leading to severe stroke and poor outcomes. This study aimed to compare stroke outcomes between NOACs withdrawal and other prior medication statuses in patients with non-valvular atrial fibrillation (NVAF). Methods: Consecutive patients who had pre-existing NVAF and were admitted for an acute ischemic stroke or transient ischemic attack- at five hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with subtherapeutic intensity, warfarin with therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groups Results: Among 719 patients with NVAF, The median NIHSS score at admission was 5 (IQR 1-13). The NOAC withdrawal group had the highest median NIHSS scores at stroke onset [16, interquartile range, IQR (1-17)], followed by the warfarin withdrawal group [11, IQR (1-14, 18)], the no antithrombotic group [5, IQR (1-13, 18, 19)], and the warfarin with subtherapeutic intensity group [5, IQR (1-10, 18, 19)]. A Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% confidence interval 0.384-8.906, P = 0.033). The median interval from drug withdrawal to ischemic stroke or TIA was 7 days (IQR 4-15) in the NOAC group. Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes.

Differential impact of white matter hyperintensities on long-term outcomes in ischemic stroke patients with large artery atherosclerosis.

BACKGROUND: The presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH. METHODS: We investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6-9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ≥ 3. RESULTS: Among 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12-2.00, p = 0.007) higher death rate compared to those without. In the older age group (≥65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15-2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association. CONCLUSION: The degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.