Predicting Atrial Fibrillation in Primary Care Using Machine Learning

Abstract

Background: Atrial fibrillation (AF) is the most common sustained heart arrhythmia. Difficulties in diagnosing AF - particularly when paroxysmal and asymptomatic - and lack of routine screening contribute to underdiagnoses. Efficient, cost-effective detection of the undiagnosed may be supported by risk-prediction models relating patient factors to AF risk. However, there exists a need for an implementable risk model that is contemporaneous and informed by routinely collected patient data, reflecting the real-world pathology of AF. Methods: Machine learning and conventional statistical models were evaluated using patients identified from UK healthcare records, aged ≥30 years, without a history of AF, from January-2006 to December-2016. A matched case-control study evaluated published risk models (Framingham, ARIC, CHARGE-AF), machine learning models using baseline and time-updated information (neural network, LASSO, random forests, support vector machines) and Cox regression. Models were ranked with maximal discrimination between AF and non-AF cases (area under the receiver operating characteristic curve, AUROC) and potential number-needed-to-screen (NNS) to detect a case of AF. Findings: Analysis of 2,994,837 patients (3.2% AF) identified time-varying neural networks as the optimal model. Compared to the best existing model CHARGE-AF, the optimal model achieved an AUROC of 0.827 vs. 0.725, with NNS of 9 vs. 13 patients at 75% sensitivity. The optimal model confirmed known baseline risk factors (age, previous cardiovascular disease, antihypertensive medication usage) and identified additional time-varying predictors previously unknown (recency of cardiovascular events, body mass index (both levels and changes), pulse pressure, and the frequency of blood pressure measurements). Interpretation: The optimal time-varying machine learning model exhibited greater predictive performance than existing AF risk models and reflected known and new relationships between patient risk factors for AF. If utilised, the model may help improve the precision of AF screening, leading to better patient outcomes and cost-effective use of healthcare resources. Funding: Bristol-Myers Squibb and Pfizer. Declaration of Interest: NR Hill, U Farooqui, & S Lister are employees of Bristol-Myers Squibb Company. M Lumley is an employee of Pfizer Inc. D Ayoubkhani, P McEwan, D M Sugrue, J Gordon are employed by HEOR ltd., which provides consulting and other research services to pharmaceutical, medical device, and related organizations. In their salaried positions, they work with a variety of companies and organizations, and are precluded from receiving payments or honoraria directly from these organizations for services rendered. AT Cohen reports grants and personal fees from Bristol-Myers Squibb Company and Pfizer Inc. during the conduct of the study; personal fees from Boehringer Ingelheim, grants and personal fees from Bristol-Myers Squibb Company, grants and personal fees from Daiichi-Sankyo Europe, personal fees from Johnson & Johnson, grants and personal fees from Pfizer, Inc., personal fees from Portola, personal fees from Sanofi, personal fees from XO1, personal fees from Janssen, personal fees from ONO Pharmaceuticals, and grants and personal fees from Bayer AG, outside the submitted work. A Bakhai reports personal fees from Bristol-Myers Squibb Company and Pfizer Inc. during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Bristol-Myers Squibb Company, personal fees from Daiichi-Sankyo Europe, personal fees from Johnson & Johnson, personal fees from Pfizer, Inc., personal fees from Novartis, personal fees from Sanofi, personal fees from MSD, personal fees from Janssen, personal fees from Roche, and personal fees from Bayer AG, outside the submitted work. DA Clifton reports personal fees from Bristol-Myers Squibb Company during the conduct of the study; and outside the submitted work, personal fees from Drayson Health (now Sensyne Health), personal fees from Ferrovial plc., personal fees from Quanta Dialysis, and personal fees from BioBeats Ltd. M O’Neill reports personal fees from Bristol-Myers Squibb Company and Pfizer Inc. during the conduct of the study; grants and personal fees from Biosense Webster, grants and personal fees from Abbott, personal fees from Siemens, personal fees from Vytronus, personal fees from Medtronic outside the submitted work. Ethical Approval: The study protocol was reviewed and approved by the Independent Scientific Advisory Committee for MHRA database research (ISAC, reference number 17_151).