Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

Machine-Learning-Derived Model for the Stratification of Cardiovascular risk in Patients with Ischemic Stroke

Background Stratification of cardiovascular risk in patients with ischemic stroke is important as it may inform management strategies. We aimed to develop a machine-learning-derived prognostic model for the prediction of cardiovascular risk in ischemic stroke patients. Materials and Methods: Two prospective stroke registries with consecutive acute ischemic stroke patients were used as training/validation and test datasets. The outcome assessed was major adverse cardiovascular event, defined as non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death during 2-year follow-up. The variables selection was performed with the LASSO technique. The algorithms XGBoost (Extreme Gradient Boosting), Random Forest and Support Vector Machines were selected according to their performance. The evaluation of the classifier was performed by bootstrapping the dataset 1000 times and performing cross-validation by splitting in 60% for the training samples and 40% for the validation samples. Results: The model included age, gender, atrial fibrillation, heart failure, peripheral artery disease, arterial hypertension, statin treatment before stroke onset, prior anticoagulant treatment (in case of atrial fibrillation), creatinine, cervical artery stenosis, anticoagulant treatment at discharge (in case of atrial fibrillation), and statin treatment at discharge. The best accuracy was measured by the XGBoost classifier. In the validation dataset, the area under the curve was 0.648 (95%CI:0.619–0.675) and the balanced accuracy was 0.58 ± 0.14. In the test dataset, the corresponding values were 0.59 and 0.576. Conclusions: We propose an externally validated machine-learning-derived model which includes readily available parameters and can be used for the estimation of cardiovascular risk in ischemic stroke patients. © 2021 Elsevier Inc

Adherence to oral anticoagulation in ischemic stroke patients with atrial fibrillation

Background: Non-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved. Aims: We sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF). Methods: We recruited hospitalised patients (2013–2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA2DS2-VASc and SAMe-TT2R2 scores with poor adherence. Results: Among 396 patients (median age 75.0 years, interquartile range [IQR] 70–80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12–33]; median ARMS score 17 [IQR 17–19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA2DS2-VASc and SAMe-TT2R2 scores were not associated with poor adherence. Conclusions: Adherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.KEY MESSAGES Adherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke. Independent patient-related factors rather than composite scores were associated with poor adherence. The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source.

To investigate the association between the presence of ipsilateral nonstenotic carotid plaques and the rate of detection of atrial fibrillation (AF) during follow-up in patients with embolic strokes of undetermined source (ESUS). We pooled data of all consecutive ESUS patients from 3 prospective stroke registries. Multivariate stepwise regression assessed the association between the presence of nonstenotic carotid plaques and AF detection. The 10-year cumulative probabilities of AF detection were estimated by the Kaplan-Meier product limit method. Among 777 patients followed for 2,642 patient-years, 341 (38.6%) patients had an ipsilateral nonstenotic carotid plaque. AF was detected in 112 (14.4%) patients in the overall population during follow-up. The overall rate of AF detection was 8.5% in patients with nonstenotic carotid plaques (2.9% per 100 patient-years) and 19.0% in patients without (5.0% per 100 patient-years) (unadjusted hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.37-0.84). The presence of ipsilateral nonstenotic carotid plaques was associated with lower probability for AF detection (adjusted HR 0.57, 95% CI 0.34-0.96, p = 0.03). The 10-year cumulative probability of AF detection was lower in patients with ipsilateral nonstenotic carotid plaques compared to those without (34.5%, 95% CI 21.8-47.2 vs 49.0%, 95% CI 40.4-57.6 respectively, log-rank-test: 11.8, p = 0.001). AF is less frequently detected in ESUS patients with nonstenotic carotid plaques compared to those without. NCT02766205

External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation.

Background and Purpose- The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods- In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results- In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions- The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice

Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source

OBJECTIVE: To investigate the association between the presence of ipsilateral nonstenotic carotid plaques and the rate of detection of atrial fibrillation (AF) during follow-up in patients with embolic strokes of undetermined source (ESUS). METHODS: We pooled data of all consecutive ESUS patients from 3 prospective stroke registries. Multivariate stepwise regression assessed the association between the presence of nonstenotic carotid plaques and AF detection. The 10-year cumulative probabilities of AF detection were estimated by the Kaplan-Meier product limit method. RESULTS: Among 777 patients followed for 2,642 patient-years, 341 (38.6%) patients had an ipsilateral nonstenotic carotid plaque. AF was detected in 112 (14.4%) patients in the overall population during follow-up. The overall rate of AF detection was 8.5% in patients with nonstenotic carotid plaques (2.9% per 100 patient-years) and 19.0% in patients without (5.0% per 100 patient-years) (unadjusted hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.37-0.84). The presence of ipsilateral nonstenotic carotid plaques was associated with lower probability for AF detection (adjusted HR 0.57, 95% CI 0.34-0.96, p = 0.03). The 10-year cumulative probability of AF detection was lower in patients with ipsilateral nonstenotic carotid plaques compared to those without (34.5%, 95% CI 21.8-47.2 vs 49.0%, 95% CI 40.4-57.6 respectively, log-rank-test: 11.8, p = 0.001). CONCLUSIONS: AF is less frequently detected in ESUS patients with nonstenotic carotid plaques compared to those without. CLINICALTRIALSGOV IDENTIFIER: NCT02766205. © 2019 American Academy of Neurology

Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source

OBJECTIVE: To investigate the association between the presence of ipsilateral nonstenotic carotid plaques and the rate of detection of atrial fibrillation (AF) during follow-up in patients with embolic strokes of undetermined source (ESUS). METHODS: We pooled data of all consecutive ESUS patients from 3 prospective stroke registries. Multivariate stepwise regression assessed the association between the presence of nonstenotic carotid plaques and AF detection. The 10-year cumulative probabilities of AF detection were estimated by the Kaplan-Meier product limit method. RESULTS: Among 777 patients followed for 2,642 patient-years, 341 (38.6%) patients had an ipsilateral nonstenotic carotid plaque. AF was detected in 112 (14.4%) patients in the overall population during follow-up. The overall rate of AF detection was 8.5% in patients with nonstenotic carotid plaques (2.9% per 100 patient-years) and 19.0% in patients without (5.0% per 100 patient-years) (unadjusted hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.37-0.84). The presence of ipsilateral nonstenotic carotid plaques was associated with lower probability for AF detection (adjusted HR 0.57, 95% CI 0.34-0.96, p = 0.03). The 10-year cumulative probability of AF detection was lower in patients with ipsilateral nonstenotic carotid plaques compared to those without (34.5%, 95% CI 21.8-47.2 vs 49.0%, 95% CI 40.4-57.6 respectively, log-rank-test: 11.8, p = 0.001). CONCLUSIONS: AF is less frequently detected in ESUS patients with nonstenotic carotid plaques compared to those without. CLINICALTRIALSGOV IDENTIFIER: NCT02766205. © 2019 American Academy of Neurology

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score.

Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; -1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; -3 points for left ventricular ejection fraction <35%; 1 point for the presence of any supraventricular extrasystole recorded during all available 12-lead standard electrocardiograms performed during hospitalization for the ESUS; -2 points for subcortical infarct; -3 points for the presence of non-stenotic carotid plaques. The rate of new incident AF during follow-up was 1.97% among the 42.3% of the cohort who had a score of ≤0, compared to 26.9% in patients with > 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. URL: https://www.clinicaltrials.gov/ Unique identifier: NCT02766205

Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source

Background: We aimed to assess the prevalence and degree of overlap of potential embolic sources (PES) in patients with embolic stroke of undetermined source (ESUS). Methods and Results: In a pooled data set derived from 3 prospective stroke registries, patients were categorized in ≥1 groups according to the PES that was/were identified. We categorized PES as follows: atrial cardiopathy, atrial fibrillation diagnosed during follow-up, arterial disease, left ventricular disease, cardiac valvular disease, patent foramen ovale, and cancer. In 800 patients with ESUS (43.1% women; median age, 67.0 years), 3 most prevalent PES were left ventricular disease, arterial disease, and atrial cardiopathy, which were present in 54.4%, 48.5%, and 45.0% of patients, respectively. Most patients (65.5%) had >1 PES, whereas only 29.7% and 4.8% of patients had a single or no PES, respectively. In 31.1% of patients, there were ≥3 PES present. On average, each patient had 2 PES (median, 2). During a median follow-up of 3.7 years, stroke recurrence occurred in 101 (12.6%) of patients (23.3 recurrences per 100 patient-years). In multivariate analysis, the risk of stroke recurrence was higher in the atrial fibrillation group compared with other PES, but not statistically different between patients with 0 to 1, 2, or ≥3 PES. Conclusions: There is major overlap of PES in patients with ESUS. This may possibly explain the negative results of the recent large randomized controlled trials of secondary prevention in patients with ESUS and offer a rationale for a randomized controlled trial of combination of anticoagulation and aspirin for the prevention of stroke recurrence in patients with ESUS. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02766205. © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score

Background and aims: Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. Methods: We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. Results: Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; −1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; −3 points for left ventricular ejection fraction 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. Conclusions: The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. Clinical trial registration: URL: https://www.clinicaltrials.gov/ Unique identifier: NCT02766205. © 2020 World Stroke Organization