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      Atrial Fibrillation Burden Signature and Near-Term Prediction of Stroke : A Machine Learning Analysis

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          Abstract

          Background:

          Atrial fibrillation (AF) increases the risk of stroke 5-fold and there is rising interest to determine if AF severity or burden can further risk stratify these patients, particularly for near-term events. Using continuous remote monitoring data from cardiac implantable electronic devices, we sought to evaluate if machine learned signatures of AF burden could provide prognostic information on near-term risk of stroke when compared to conventional risk scores.

          Methods and Results:

          We retrospectively identified Veterans Health Administration serviced patients with cardiac implantable electronic device remote monitoring data and at least one day of device-registered AF. The first 30 days of remote monitoring in nonstroke controls were compared against the past 30 days of remote monitoring before stroke in cases. We trained 3 types of models on our data: (1) convolutional neural networks, (2) random forest, and (3) L1 regularized logistic regression (LASSO). We calculated the CHA 2 DS 2 -VASc score for each patient and compared its performance against machine learned indices based on AF burden in separate test cohorts. Finally, we investigated the effect of combining our AF burden models with CHA 2 DS 2 -VASc. We identified 3114 nonstroke controls and 71 stroke cases, with no significant differences in baseline characteristics. Random forest performed the best in the test data set (area under the curve [AUC]=0.662) and convolutional neural network in the validation dataset (AUC=0.702), whereas CHA 2 DS 2 -VASc had an AUC of 0.5 or less in both data sets. Combining CHA 2 DS 2 -VASc with random forest and convolutional neural network yielded a validation AUC of 0.696 and test AUC of 0.634, yielding the highest average AUC on nontraining data.

          Conclusions:

          This proof-of-concept study found that machine learning and ensemble methods that incorporate daily AF burden signature provided incremental prognostic value for risk stratification beyond CHA 2 DS 2 -VASc for near-term risk of stroke.

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          Most cited references25

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          Human-level control through deep reinforcement learning.

          The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.
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            Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association

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              Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.

              Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included. We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF. Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores (P value for trend = .003). Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS(2) schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF.
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                Author and article information

                Journal
                Circulation: Cardiovascular Quality and Outcomes
                Circ: Cardiovascular Quality and Outcomes
                Ovid Technologies (Wolters Kluwer Health)
                1941-7713
                1941-7705
                October 2019
                October 2019
                : 12
                : 10
                Affiliations
                [1 ]Biomedical Informatics Training Program (L.H., S.M.N.), Stanford University, CA.
                [2 ]Veterans Affairs Palo Alto Health Care System, Palo Alto, CA (M.A., S.K.S., J.F., M.P.T.).
                [3 ]Department of Bioengineering (R.B.A.), Stanford University, CA.
                [4 ]Department of Genetics (R.B.A.), Stanford University, CA.
                [5 ]Quantitative Sciences Unit (J.P.B.), Stanford University School of Medicine, CA.
                [6 ]Department of Medicine (S.M.N.), Stanford University School of Medicine, CA.
                [7 ]Center for Digital Health (M.P.T.), Stanford University School of Medicine, CA.
                Article
                10.1161/CIRCOUTCOMES.118.005595
                31610712
                1e01ef47-0c0e-400b-9a4d-61ff639a5c6c
                © 2019
                History

                Quantitative & Systems biology,Biophysics
                Quantitative & Systems biology, Biophysics

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