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Introduction: The D-dimer to fibrinogen ratio (DFR) is a good indicator of clot-producing activity in thrombotic disease, but its clinical usefulness in stroke patients with nonvalvular atrial fibrillation (NVAF) has not been studied. We evaluated the association between the DFR and early neurological deterioration (END) in acute ischemic stroke (AIS) patients with NVAF., Methods: We included consecutive AIS patients with NVAF between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. END was defined as an increase ≥2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. The DFR was calculated as follows: DFR = D-dimer (mg/L)/fibrinogen (mg/dL) x 100., Results: A total of 1018 AIS patients with NVAF were evaluated. In multivariable logistic regression analysis, the highest DFR tertile was closely associated with END (adjusted odds ratio [aOR] = 2.14, 95 % confidence interval [CI]: 1.24-3.69). Hypertension (aOR = 1.71, 95 % CI: 1.09-2.70), initial NIHSS score (aOR = 1.05, 95 % CI: 1.02-1.07) and use of anticoagulants (aOR = 0.41, 95 % CI: 0.28-0.60) were also correlated with END. In addition to END, the DFR was correlated with discharge NIHSS and modified Rankin Scale (mRS) scores and the 3-month mRS score., Conclusions: High DFR values were associated with END in AIS patients with NVAF. As the DFR is an indicator directly related to the main pathological mechanism of NVAF patients (fibrinolysis and coagulation), it may be useful in predicting their prognosis., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The underlying etiology of intracranial non-occlusive intraluminal thrombus (iNOT) remains unknown. This study aimed to investigate whether the presence of iNOT can indicate the underlying etiology of large vessel occlusion (LVO) in patients undergoing endovascular therapy (EVT)., Methods: Among patients who underwent EVT at three comprehensive stroke centers, we included those with intracranial LVO in the anterior circulation. The presence of iNOT was determined by pretreatment DSA. We investigated the association between iNOT and intracranial atherosclerotic stenosis (ICAS) related LVO., Results: Of 546 patients, 44 (8.1%) had iNOT. Patients with iNOT were younger, had less hypertension, atrial fibrillation, and a history of antiplatelet use. In addition, the involvement of the M1 segment of the middle cerebral artery (MCA) was more frequent. However, they had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission and longer onset to recanalization time compared with patients with no iNOT. In a logistic regression model adjusting for age, sex, atrial fibrillation, smoking, prior antiplatelet and anticoagulant use, intravenous tissue plasminogen activator, NIHSS on admission, number of technical trials, intraprocedural re-occlusion, and the location of LVO (p<0.10 in the univariate analysis), the presence of iNOT was significantly associated with ICAS related LVO (adjusted OR 3.04; 95% CI 1.33 to 6.90; p=0.007)., Conclusions: The presence of iNOT may reflect an underlying ICAS related LVO in patients undergoing EVT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Unlike patients with stroke caused by other mechanisms, the effect of elevated plasma total homocysteine (tHcy) on the prognosis of patients with both ischemic stroke and atrial fibrillation (AF) is unknown. This study aimed to evaluate the association between tHcy level and the functional outcome of patients with AF-related stroke. Methods and Results We included consecutive patients with AF-related stroke between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. A 3-month modified Rankin Scale score ≥3 was considered an unfavorable outcome. Since tHcy is strongly affected by renal function, we performed a subgroup analysis according to the presence of renal dysfunction. A total of 910 patients with AF-related stroke were evaluated (mean age, 73 years; male sex, 56.0%). The mean tHcy level was 11.98±8.81 μmol/L. In multivariable analysis, the tHcy level (adjusted odds ratio, 1.04; 95% CI, 1.01-1.07, per 1 μmol/L) remained significantly associated with unfavorable outcomes. In the subgroup analysis based on renal function, tHcy values above the cutoff point (≥14.60 μmol/L) showed a close association with the unfavorable outcome only in the normal renal function group (adjusted odds ratio, 3.10; 95% CI, 1.60-6.01). In patients with renal dysfunction, tHcy was not significantly associated with the prognosis of AF-related stroke. Conclusions A higher plasma tHcy level was associated with unfavorable outcomes in patients with AF-related stroke. This positive association may vary according to renal function but needs to be verified in further studies.

Abstract: The performance of scoring systems for risk stratification in patients with atrial fibrillation (AF) was not validated well in patients with stroke. The purpose of this study was to evaluate whether the risk scoring systems predict vascular outcomes in stroke patients with AF.Data were obtained from a nationwide multicenter registry for acute stroke with AF from January 1, 2013, to December 31, 2015. We investigated the predictive power of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke scores in stroke patients with AF. The subjects were further stratified into groups according to treatment with or without oral anticoagulants (OACs).A total of 3112 stroke with AF subjects were included. The rate of recurrent ischemic stroke and any stroke were not associated with the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores. The risks of death and major adverse cerebrovascular and cardiovascular events (MACEs) increased sequentially with the increase of each risk score in OAC group. (the range of C-index 0.544-0.558 for recurrent ischemic stroke; 0.523-0.537 for any stroke; 0.580-0.597 for death; 0.564-0.583 for MACEs). However, in the group treated with OACs, all risk scores were significantly associated with the risk of MACEs. The C-statistics of the 4 scoring systems were 0.544 to 0.558, 0.523 to 0.537, 0.580 to 0.597, 0.564 to 0.583, respectively, for recurrent ischemic stroke, any stroke, death, and MACEs.The performance of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores for the prediction of recurrent stroke was unsatisfactory in stroke patients with AF whereas the performance for the prediction of recurrent stroke was not MACEs or death was good. A new risk stratification scheme that is specific for secondary stroke prevention in the AF population is needed., Competing Interests: The other authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Serum cardiac troponin I (cTnI) is often elevated in patients with ischemic stroke, and is associated with their prognosis. Since cTnI is also closely related to atrial fibrillation (AF), cTnI may be a sensitive prognostic indicator in patients with AF-related stroke. This study aimed to evaluate the association between serum cTnI and early neurological deterioration (END) in patients with AF-related stroke. We included consecutive AF-related stroke patients between 2013 and 2015. END was defined as an increase ≥ 2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. A total of 1,133 patients with AF-related stroke were evaluated. In multivariable analysis, cTnI [adjusted odds ratio (aOR) = 1.16, 95% confidence interval (CI) 1.00-1.34; P = 0.047] remained significant after adjusting for confounders. Initial NIHSS score (aOR = 1.03, 95% CI 1.00-1.06; P = 0.043) was also positively associated with END; meanwhile, the use of anticoagulants was negatively associated in both vitamin K antagonists (aOR = 0.35, 95% CI 0.23-0.54; P < 0.001) and new oral anticoagulants (aOR = 0.41, 95% CI 0.19-0.89; P = 0.024). In conclusion, higher serum cTnI was associated with END in patients with AF-related stroke.

Background There is insufficient evidence on the effect of statins, particularly high-intensity statins, in patients with acute ischemic stroke and atrial fibrillation. We investigated the impact of statins on the outcomes in these patients, including those who might be vulnerable to statin therapy and those without clinical atherosclerotic cardiovascular diseases. Methods and Results A total of 2153 patients with acute ischemic stroke and atrial fibrillation were enrolled in the present nationwide, multicenter, cohort study. The primary composite end point was the occurrence of net adverse clinical and cerebral events (NACCE; death from any cause, stroke, acute coronary syndrome, or major bleeding) over a 3-year period based on statin intensity. NACCE rates were lower in patients receiving low- to moderate-intensity (adjusted hazard ratio 0.64; 95% CI: 0.52-0.78) and high-intensity statins (hazard ratio 0.51; 95% CI 0.40-0.66) than in those not receiving statin therapy. High-intensity statins were associated with a lower risk for NACCE than low- to moderate-intensity statins (hazard ratio 0.76; 95% CI 0.59-0.96). Subgroup analyses showed that the differences in hazard ratio for 3-year NACCE favored statin use across all subgroups, including older patients, those with low cholesterol levels, patients receiving anticoagulants, and patients without clinical atherosclerotic cardiovascular diseases. Magnified benefits of high-intensity statins compared with low- to moderate-intensity statins were observed in patients who underwent revascularization therapy and those under 75 years of age. Conclusions Statins, particularly high-intensity statins, could reduce the risk for NACCE in patients with acute ischemic stroke and atrial fibrillation; this needs to be further explored in randomized controlled trials.

Objectives: To investigate the predictors of hemorrhagic transformation (HT) in patients with mild atrial fibrillation-related stroke who were treated with early anticoagulation. We conducted a post-hoc subgroup analysis from Acute Cerebral Infarction Patients with Non-valvular Atrial Fibrillation (Triple AXEL) study., Patients and Methods: The Triple AXEL study was a randomized, multicenter, open-label, blinded end-point evaluation, comparative phase 2 trial. To identify the relationship between the type of HT and risk factors. We analyzed various factors using data from the Triple AXEL study, such as sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, initial infarction volume, initial infarction location, and new intracranial hemorrhage on follow-up gradient recalled echo or susceptibility-weighted imaging., Results: We analyzed various factors by dividing patients into a new HT group and a no HT group. No correlation was found between HT and risk factors that were significantly associated with HT, including age, sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, and initial infarction volume. When the initial infarction was classified into anterior circulation infarction (ACI) and posterior circulation infarction (PCI), the occurrence of new HT was significantly more associated with PCI than with ACI (57.6% vs 24.0%, P = 0.001). Multivariate logistic regression analysis was performed using HT as a response variable. Only the location of initial infarction according to the vascular territory contributed to the increased risk of HT (OR2.3, 95%CI1.33-3.91, P = 0.003)., Conclusion: PCI is a very important independent risk factor for HT in patients with mild AF-related stroke treated with early anticoagulation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Importance: In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear., Objective: To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke., Design, Setting, and Participants: A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis., Interventions: Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks., Main Outcomes and Measures: The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length., Results: Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001)., Conclusions and Relevance: In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy., Trial Registration: clinicaltrials.gov Identifier: NCT02042534.

Background: Ischemic stroke with atrial fibrillation (AF) may recur despite appropriate treatment. It may be AF-related or AF-unrelated. We compared the factors associated with AF-related and AF-unrelated recurrences among ischemic stroke patients with AF. Methods: Patients with ischemic stroke and AF were enrolled from 11 centers in Korea. Ischemic stroke recurrence was classified as AF-related if the lesion pattern was compatible with cardioembolism without significant stenosis or as AF-unrelated if the lesion was more likely due to small vessel disease or arterial stenosis. Factors associated with stroke recurrence (AF-related and AF-unrelated) were investigated. Results: Among the 2,239 patients, 115 (5.1%) experienced recurrence (75 AF-related and 40 AF-unrelated). Factors independently associated with any stroke recurrence included AF diagnosed before stroke, small subcortical infarctions, and small scattered lesions in a single vascular territory. Type of AF was associated with the type of stroke recurrence, with persistent AF being associated with AF-related stroke [hazard ratio (HR) = 2.94, 95% confidence interval (CI) 1.69–5.26; p < 0.001]. By contrast, paroxysmal AF (HR = 3.76, 95% CI 1.56–9.04; p = 0.003), AF diagnosed before stroke (HR = 2.38, 95% CI 1.19–4.55; p = 0.014), small scattered lesions in a single vascular territory (reference: corticosubcortical lesion, HR = 3.19, 95% CI 1.18–8.63; p = 0.022), and the use of antiplatelet agents (HR = 2.11, 95% CI 1.11–4.03; p = 0.024) were independently associated with AF-unrelated stroke. Conclusion: Persistent AF was more associated with AF-related stroke recurrence, whereas paroxysmal AF was more associated with AF-unrelated stroke recurrence. A scattered lesion in a single vascular territory may predict AF-unrelated stroke recurrence. [ABSTRACT FROM AUTHOR]

We aimed to develop a novel prediction model for early neurological deterioration (END) based on an interpretable machine learning (ML) algorithm for atrial fibrillation (AF)-related stroke and to evaluate the prediction accuracy and feature importance of ML models. Data from multicenter prospective stroke registries in South Korea were collected. After stepwise data preprocessing, we utilized logistic regression, support vector machine, extreme gradient boosting, light gradient boosting machine (LightGBM), and multilayer perceptron models. We used the Shapley additive explanation (SHAP) method to evaluate feature importance. Of the 3,213 stroke patients, the 2,363 who had arrived at the hospital within 24 h of symptom onset and had available information regarding END were included. Of these, 318 (13.5%) had END. The LightGBM model showed the highest area under the receiver operating characteristic curve (0.772; 95% confidence interval, 0.715–0.829). The feature importance analysis revealed that fasting glucose level and the National Institute of Health Stroke Scale score were the most influential factors. Among ML algorithms, the LightGBM model was particularly useful for predicting END, as it revealed new and diverse predictors. Additionally, the effects of the features on the predictive power of the model were individualized using the SHAP method. [ABSTRACT FROM AUTHOR]

Background: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. Objective: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. Methods: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. Results: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04–1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04–1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01–1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. Conclusions: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS. [ABSTRACT FROM AUTHOR]

Background and aims: Atrial fibrillation (AF) is a major cause of ischemic stroke; however, detailed clinical data and prognostic factors for stroke patients with AF are lacking in Korea. We aimed to investigate clinical information and factors associated with functional outcomes of stroke patients with AF from the Korean nationwide ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) database. Methods: From January 2013 to December 2015, consecutive clinical information from acute stroke patients with AF or history of AF was collected from 11 centers in Korea. Collected data included demographics, risk factors, pre-stroke medication, stroke severity, stroke subtypes, concomitant cerebral atherosclerosis, brain image findings, recanalization therapy, discharge medication, and functional outcome at 3 months after index stroke. Results: A total of 3,213 stroke patients (mean age, 73.6 ± 9.8 years; female, 48.6%) were included. The mean CHA2DS2-VASc score was 4.9. Among the 1,849 (57.5%) patients who had brain image and functional outcome data, poor outcome (modified Rankin scale > 2) was noted in 53.1% (981/1,849) of patients. After adjusting for age, sex, and variables that had a p < 0.05 in univariate analysis or well-known factors for functional outcome, presence of asymptomatic extracranial cerebral atherosclerosis [odd ratio (OR): 1.96, 95% confidence interval (CI): 1.36–2.82, p = 0.001] and less frequent prior stroke statin intake (OR: 0.69, 95% CI: 0.49–0.98, p = 0.038) were associated with poor functional outcome. Conclusion: Our results suggest that presence of non-relevant extracranial cerebral atherosclerosis may affect poor functional outcome and prior stroke statin therapy may be feasible in Korean stroke patients with AF. [ABSTRACT FROM AUTHOR]

Background: We investigated the effect of D-dimer levels and efficacy of different antithrombotic therapies according to the baseline D-dimer levels on recurrent stroke in patients with atrial fibrillation (AF)-related stroke and atherosclerosis. Methods: We enrolled 1441 patients with AF-related stroke and atherosclerosis in this nationwide multicenter study. The primary outcome measure was the occurrence of recurrent ischemic stroke over a 3-year period. Results: High D-dimer levels (≥2 μg/mL) were significantly associated with higher risk of recurrent ischemic stroke (adjusted hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.13–2.84; p = 0.012). The risk of recurrent stroke was similar between the anticoagulant and the antiplatelet groups in all subjects (adjusted HR, 0.78; 95% CI, 0.46–1.32; p = 0.369). However, in patients with high D-dimer levels (≥2 μg/mL), risk of recurrent stroke was significantly lower in the anticoagulant group than in the antiplatelet group (adjusted HR, 0.40; 95% CI, 0.18–0.87; p = 0.022). Conclusion: Our findings suggested that baseline D-dimer levels could be used as a risk assessment biomarker of recurrent stroke in patients with AF-related stroke and atherosclerosis. High D-dimer levels would facilitate the identification of patients who are more likely to benefit from anticoagulants to ensure secondary prevention of stroke. [ABSTRACT FROM AUTHOR]