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Background:Recent studies cast doubt on the accuracy of the most-commonly used risk scores (CHA2DS2-VASC and HAS-BLED) in differentiating the risk of acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) among patients with fibrillation (AF). Because of the importance of AIS/ICH risk determination for choice of proper preventive approaches, we aimed to compare the value of these risk scores and brain MRI markers to differentiate the occurrence of AIS and ICH in a large cohort of AF-related strokes.Methods:The Neuro-AFib study is a multicenter effort to elucidate the causes and consequences of AIS and ICH in AF patients. Demographics, CHA2DS2-VASC and HAS-BLED scores, and ischemic/hemorrhagic brain MRI markers were compared between AF patients admitted with AIS and ICH to 15 academic stroke centers in the US between 1/2018-12/2019.Results:Of 5694 stroke admissions with AF, 4826 (84.8%) had AIS and 868 (15.2%) ICH. Mean age was similar between groups (75.9±11.5 vs 76.6±11.9, p=0.1), more ICH patients were male (57% vs 50%). Pre-index event CHA2DS2-VASC (4.14±1.6 vs 4.22±1.6) and HAS-BLED (2.71±1.09 vs 2.68±1.13) were similar between groups [both p>0.2]. Cerebral microbleeds (CMB, 56% vs 33.5%), cortical superficial siderosis (cSS, 15% vs 9.4%), and moderate-to-severe leukoaraiosis (41% vs 33.4%) were more commonly found among ICH patients compared to AIS (all p<0.001). Chronic lacunar infarcts (43.5% vs 39.5%, p=0.03) and chronic non-lacunar infarcts (29% vs 18%, p<0.001) were more commonly found in AIS. In a multivariable logistic regression model that included all variables above, male sex, presence of CMBs, cSS, moderate-to-severe leukoaraiosis were associated with ICH, chronic non-lacunar infarcts with AIS (all p<0.005), while CHA2DS2-VASC (p=0.9) and HAS-BLED (p=0.9) were not related to the stroke type.Conclusions:Data from our multicenter study confirm the lack of specificity of CHA2DS2-VASC and HAS-BLED to categorize the risk of AIS vs ICH in AF patients. The chronic MRI findings (CMB, cSS, moderate-to-severe leukoaraiosis, chronic infarcts) should be incorporated into risk scores, and their predictive value for AIS and ICH should be investigated in prospective studies to select optimal stroke prevention methods in AF patients.

Background:Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulants (OAC) used to prevent ischemic strokes (IS) in patients with atrial fibrillation (AF). As different ICH etiologic factors correspond to different ICH risks, we aimed to present the causes of ICH in AF patients who were or were not using OAC, based on data from a multicenter contemporary cohort.Methods:The Neuro-AFib study is a multicenter effort to elucidate the current causes and consequences of IS and ICH in AF patients. Detailed clinical, laboratory and multimodal imaging data were collected from consecutive patients with AF admitted to 15 US stroke centers with an IS or ICH between 1/2018-12/2019. Etiologic factors of AF patients who were admitted with ICH on OAC (OAC-ICH) and off OAC (nonOAC-ICH) will be compared.Results:A total of 868 patients presented with ICH and had a diagnosis of AF, either previously known (88%) or diagnosed during admission (12%). 571 patients (66%) were on OAC at the time of their ICH of whom 58% were on direct OAC (DOAC), 40% on warfarin and 2% on heparin. OAC-ICH patients were older than nonOAC-ICH (76.6±10 vs 74.4±13, p=0.006) while sex distribution was the same in both groups (43% female). CHA2DS2-VASC was higher in OAC-ICH (4.3±1.6 vs 3.9±1.9, p=0.001) but HAS-BLED score was the same in both groups (2.7±1.1). Cerebral amyloid angiopathy (CAA) was diagnosed in 42.5% of the ICH patients based on modified Boston criteria while hypertensive cerebral small vessel disease (HTN-cSVD) in 57.5%. HTN-cSVD was the more common ICH etiology among OAC-ICH (65%) compared to nonOAC-ICH (49%). Among OAC-ICHs, DOAC-related ICHs tended to be more commonly of hypertensive etiology when compared to warfarin-ICH (p=0.09).Conclusions:Our study is the first to report the etiologic mechanisms of ICH in AF patients on or off OAC. CAA is known to be a major cause of OAC-ICH with exceedingly high recurrence rates. Despite this fact, HTN-cSVD was more common among OAC-ICH (especially DOAC-ICH) patients, supporting the view that the presence/absence of HTN-cSVD risk markers such as deep microbleeds are as important as CAA-markers in determining the optimal stroke prevention method in AF patients (left atrial appendage closure vs lifelong OAC).

Background:Ischemic stroke (IS) admissions in patients with atrial fibrillation (AF) using either direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) are commonly seen in stroke units but data on their prevalence and causes are scarce. Understanding the frequency/causes of failures of current FDA-approved preventive methods in patients with AF is important to reduce stroke risk and related death/disability.Methods:The Neuro-AFib study is a multicenter effort geared toward elucidating the causes and consequences of IS and hemorrhagic stroke in a contemporary AF cohort. Detailed clinical, laboratory and multimodal neuro- and cardiac imaging data from known AF patients consecutively admitted to 22 US academic stroke centers with an IS between 1/2018-12/2019 were used to compare characteristics of IS on vs off oral anticoagulants.Results:Out of 6443 IS patients with AF, 4898 (76%) had known AF prior to the acute stroke. Among these patients with known AF, 2204 (45%) were using oral anticoagulants [OAC= DOAC (59.3%) or VKA (40.7%)]. Patients who had IS on OAC were younger (76.8+11 vs 78+12, p=0.001), had higher mean CHA2DS2-VASc scores (4.17+1.5 vs 3.9+1.5, p<0.0001), and more likely to have a past history of IS/TIA when compared to non-OAC group (35% vs 23%, p<0.0001). In a multivariable logistic regression model, history of IS/TIA, diabetes, hyperlipidemia, heart failure, prosthetic heart valve, sleep apnea, permanent atrial fibrillation, left atrial dilation and ischemic arterial disease were all independently associated with IS on OAC (all p<0.05). Imaging data were complete in 15% of the cohort and IS on OAC group had more acute lacunar infarcts, and extracranial and intracranial atherosclerotic disease causing 50% or more ipsilateral stenosis compared to patients with IS off OAC (all p<0.05).Conclusions:Based on a large multicenter contemporary cohort of IS patients with known AF, the numbers of patients who failed OACs (and especially DOACs) are high. These patients have severe vascular risk factor loads, concurrent etiologies, and they are more likely to have recurrent ischemic events. Further detailed data focused on imaging and IS mechanisms from this contemporary cohort will be ready to be presented during ISC 2022.

Background:Underuse of FDA-approved stroke prevention methods in atrial fibrillation (AF) remains a major problem. We aimed to explore the potential causes of oral anticoagulant (OAC) non-use and compare the frequency of these factors between AF patients with acute ischemic stroke (AIS) off and on oral anticoagulant (OAC).Methods:The Neuro-AFib study is a multicenter observational study aiming to clarify the causes of different stroke types in a contemporary AF cohort. Potential causes of OAC non-use were systematically collected from all enrolled patients based on the exclusion criteria of the Direct OAC (DOAC) studies. The frequency of potential causes of OAC non-use (AIS-off-OAC) are explored in AF patients consecutively admitted to 22 US academic stroke centers with an AIS between 1/2018-12/2019, and these rates are compared to AIS-on-OAC.Results:Among 4898 patients with known AF who had IS, 2694 (55%) were not using any OAC, and 45% were AIS-on-OAC. CHA2DS2-VASc <2, the cutoff representing low embolic risk until late 2019, was found in 7% of AIS-off-OAC group compared to 3.8% in AIS-on-OAC (p<0.0001). The most common factor in OAC non-use group was history of falls (26%) vs 18% in AIS-on-OAC group (p=0.004). History of bleeding [intracranial (2.3%) and extracranial (18.5%)] was found in 20.8% of AIS-off-OAC vs 10.4% of AIS-on-OAC group (p<0.0001). 82.6% of these hemorrhages were classified as major bleeds. Pre-stroke cognitive impairment was also common in AIS-off-OAC (21.7%). Renal failure (creatinine >2mg/dl) was found in 13% of AIS-off-OAC. Gait problems leading to limited mobility (10%) and excessive alcohol use (3.8%) were other potential factors for OAC non-use. Among OAC non-users, 64% had at least one risk factor defined above.Conclusions:In a large multicenter contemporary IS cohort with known AF, 55% of patients were not on OAC, and about two thirds of them had a reason that would exclude them from the phase 3 DOAC studies. Other than improving the accuracy of risk prediction algorithms, research should focus on identifying optimal management approaches for this large AF population who present challenges to lifelong OAC use. FDA-approved left atrial appendage closure procedures can be considered in such AF patients.

Background:We aimed to compare the clinical features and short-term outcomes of hemorrhagic stroke (HS) to ischemic stroke (IS) in atrial fibrillation (AF) patients using a large contemporary cohort.Methods:The Neuro-AFib study is a multicenter effort to elucidate the current causes and consequences of IS and HS in AF patients. The retrospective phase of the study is underway, aimed at obtaining detailed clinical, laboratory and multimodal neuro- and cardiac imaging data from ~9,000 patients with AF admitted to 30 academic stroke centers in the US with an IS or HS between 1/2018-12/2019. Preliminary clinical data from 12 sites are presented in this abstract.Results:Of 4764 stroke admissions with AF, 820 (17.2%) had HS and 3944 IS. Patients with HS were younger (74.8+12 vs 76.8+12), more likely to be male (54% vs 46%) and had lower CHA2DS2-VASC (3.6+1.6 vs 3.9+1.6) than IS [all p<0.05]. Patients with HS were more likely to be on AC compared to IS (60% vs 38%, p<0.001). Within the HS cohort, 32% were on direct oral anticoagulant, 28% on warfarin, 16% on antiplatelet, and 24% on no antithrombotic. Patients with HS had worse outcomes than IS in terms of in hospital case fatality (32.4 vs 10.3%, p<0.001) and severe disability (modified Rankin Scale 4-5) at discharge (63.3% vs 53.7%, p=0.002) despite similar rates of severe disability before admission (7% vs 6.2%, p=0.73). All of the reported associations remained significant after adjustment for age, sex and other relevant covariates.Conclusions:Preliminary findings from the Neuro-AFib study show significantly worse outcomes for HS compared to IS in AF patients, with triple case fatality and elevated severe disability risks. These results showcase the importance of identifying AF patients at high HS risk. Detailed imaging markers of HS risk including microbleeds, superficial siderosis, leukoaraiosis within the full cohort will be analyzed and discussed during ISC 2021.

Background:An estimated 150,000 atrial fibrillation (AF) patients suffer an ischemic stroke (IS) annually in the US. Understanding the frequency/causes of underuse and failures of current FDA-approved preventive methods in patients with known AF may reduce stroke risk and related death/disability.Methods:The Neuro-AFib study is a multicenter effort geared toward elucidating the causes and consequences of IS and hemorrhagic stroke (HS) in a contemporary AF cohort. The retrospective phase of the study is underway, aiming to obtain detailed clinical, laboratory and multimodal neuro- and cardiac imaging data from ~9,000 AF patients admitted to 30 US academic stroke centers with an IS or HS between 1/2018-12/2019. Clinical data of IS admissions from 12 sites will be discussed. Disability is defined as a modified Rankin Score (mRS) 3-5, outcomes are from the time of hospital discharge.Results:A total of 3944 AF patients presented with an IS, mean age was 76.8+12, and 50.2% were female. AF was diagnosed prior to IS in 78% of patients. Data on prestroke antithrombotic usage, embolic risk scores, clinical stroke severity and outcomes are presented in the FIGURE.Conclusions:Preliminary results from the Neuro-AFib study show high rates of underuse of approved stroke prevention measures (54%) and anticoagulant failures (46%) that result into IS even in known AF patients. Relatively high rates of pre-stroke AF detection failures were also noted (22%). Death/disability rates were high in all of these AF-related IS patients (>69%). Detailed data collection focused on imaging and lab markers of stroke risk from this contemporary cohort will be ready to be presented during ISC 2021.