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      Computational models of atrial fibrillation: achievements, challenges, and perspectives for improving clinical care

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          Abstract

          Despite significant advances in its detection, understanding and management, atrial fibrillation (AF) remains a highly prevalent cardiac arrhythmia with a major impact on morbidity and mortality of millions of patients. AF results from complex, dynamic interactions between risk factors and comorbidities that induce diverse atrial remodelling processes. Atrial remodelling increases AF vulnerability and persistence, while promoting disease progression. The variability in presentation and wide range of mechanisms involved in initiation, maintenance and progression of AF, as well as its associated adverse outcomes, make the early identification of causal factors modifiable with therapeutic interventions challenging, likely contributing to suboptimal efficacy of current AF management. Computational modelling facilitates the multilevel integration of multiple datasets and offers new opportunities for mechanistic understanding, risk prediction and personalized therapy. Mathematical simulations of cardiac electrophysiology have been around for 60 years and are being increasingly used to improve our understanding of AF mechanisms and guide AF therapy. This narrative review focuses on the emerging and future applications of computational modelling in AF management. We summarize clinical challenges that may benefit from computational modelling, provide an overview of the different in silico approaches that are available together with their notable achievements, and discuss the major limitations that hinder the routine clinical application of these approaches. Finally, future perspectives are addressed. With the rapid progress in electronic technologies including computing, clinical applications of computational modelling are advancing rapidly. We expect that their application will progressively increase in prominence, especially if their added value can be demonstrated in clinical trials.

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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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              Stop explaining black box machine learning models for high stakes decisions and use interpretable models instead

              Black box machine learning models are currently being used for high stakes decision-making throughout society, causing problems throughout healthcare, criminal justice, and in other domains. People have hoped that creating methods for explaining these black box models will alleviate some of these problems, but trying to explain black box models, rather than creating models that are interpretable in the first place, is likely to perpetuate bad practices and can potentially cause catastrophic harm to society. There is a way forward - it is to design models that are inherently interpretable. This manuscript clarifies the chasm between explaining black boxes and using inherently interpretable models, outlines several key reasons why explainable black boxes should be avoided in high-stakes decisions, identifies challenges to interpretable machine learning, and provides several example applications where interpretable models could potentially replace black box models in criminal justice, healthcare, and computer vision.
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                Author and article information

                Journal
                Cardiovasc Res
                Cardiovasc Res
                cardiovascres
                Cardiovascular Research
                Oxford University Press
                0008-6363
                1755-3245
                15 June 2021
                23 April 2021
                23 April 2021
                : 117
                : 7
                : 1682-1699
                Affiliations
                [1 ] Department of Cardiology, Cardiovascular Research Institute Maastricht, Faculty of Health, Medicine, and Life Sciences, Maastricht University , PO Box 616, 6200 MD Maastricht, The Netherlands
                [2 ] Department of Medicine, Montreal Heart Institute and Université de Montréal , Montreal, Canada
                [3 ] Department of Pharmacology and Therapeutics, McGill University , Montreal, Canada
                [4 ] Institute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen , Duisburg, Germany
                [5 ] IHU Liryc and Fondation Bordeaux Université , Bordeaux, France
                [6 ] Alliance for Cardiovascular Diagnostic and Treatment Innovation, and Department of Biomedical Engineering, Johns Hopkins University , Baltimore, MD, USA
                [7 ] Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, MD, USA
                Author notes
                Corresponding author. Tel: +31 43 38 76046, E-mail: jordi.heijman@ 123456maastrichtuniversity.nl
                Author information
                https://orcid.org/0000-0002-1418-108X
                https://orcid.org/0000-0002-5730-2013
                https://orcid.org/0000-0003-1073-5337
                https://orcid.org/0000-0002-5565-3311
                https://orcid.org/0000-0002-8661-063X
                Article
                cvab138
                10.1093/cvr/cvab138
                8208751
                33890620
                e2dbccdb-bd00-48ed-abc6-e8df429ac58f
                © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 31 December 2020
                : 17 March 2021
                Page count
                Pages: 18
                Funding
                Funded by: Netherlands Organization for Scientific Research NWO/ZonMW;
                Award ID: 09150171910029
                Funded by: Netherlands Cardiovascular Research Initiative;
                Funded by: Dutch Heart Foundation;
                Award ID: CVON 2014-9
                Funded by: Canadian Institutes of Health Research, DOI 10.13039/501100000024;
                Award ID: 148401
                Funded by: Heart and Stroke Foundation of Canada, DOI 10.13039/100004411;
                Funded by: NIH, DOI 10.13039/100000002;
                Award ID: U01HL141074
                Award ID: R01HL142893
                Award ID: R01HL142496
                Funded by: Leducq Foundation, DOI 10.13039/501100001674;
                Funded by: Lowenstein Foundation;
                Categories
                Spotlight Reviews
                Editor's Choice
                AcademicSubjects/MED00200

                Cardiovascular Medicine
                atrial fibrillation,computer modelling,electrophysiology,in silico,personalized therapy

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