{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:25:46Z","timestamp":1787826346438,"version":"build-2784847793"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Quality and Outcomes"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Subtle, prognostically important ECG features may not be apparent to physicians. In the course of supervised machine learning, thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. We aimed to investigate whether neural network\u2013derived ECG features could be used to predict future cardiovascular disease and mortality and have phenotypic and genotypic associations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We extracted 5120 neural network\u2013derived ECG features from an artificial intelligence\u2013enabled ECG model trained for 6 simple diagnoses and applied unsupervised machine learning to identify 3 phenogroups. Using the identified phenogroups, we externally validated our findings in 5 diverse cohorts from the United States, Brazil, and the United Kingdom. Data were collected between 2000 and 2023.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              In total, 1\u2005808\u2005584 patients were included in this study. In the derivation cohort, the 3 phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared with phenogroup A (hazard ratio, 1.20 [95% CI, 1.17\u20131.23];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.0001; phenogroup A mortality, 2.2%; phenogroup B mortality, 6.1%). In univariate analyses, we found phenogroup B had a significantly greater risk of mortality in all cohorts (log-rank\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.01 in all 5 cohorts). Phenome-wide association study showed phenogroup B had a higher rate of future atrial fibrillation (odds ratio, 2.89;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.00001), ventricular tachycardia (odds ratio, 2.00;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.00001), ischemic heart disease (odds ratio, 1.44;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.00001), and cardiomyopathy (odds ratio, 2.04;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.00001). A single-trait genome-wide association study yielded 4 loci.\n              <jats:italic toggle=\"yes\">SCN10A<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">SCN5A<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">CAV1<\/jats:italic>\n              have roles in cardiac conduction and arrhythmia.\n              <jats:italic toggle=\"yes\">ARHGAP24<\/jats:italic>\n              does not have a clear cardiac role and may be a novel target.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Neural network\u2013derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circoutcomes.123.010602","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T10:00:35Z","timestamp":1731578435000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Prognostic Significance and Associations of Neural Network\u2013Derived Electrocardiographic Features"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0204-7078","authenticated-orcid":true,"given":"Arunashis","family":"Sau","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."},{"name":"Department of Cardiology, Imperial College Healthcare National Health Service Trust, London, United Kingdom (A.S., N.S.P., F.S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-8529","authenticated-orcid":true,"given":"Anto\u0302nio H.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Information Technology, Uppsala University, Sweden (A.H.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-6906","authenticated-orcid":true,"given":"Kathryn A.","family":"McGurk","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."},{"name":"Medical Research Council Laboratory of Medical Sciences (K.A.M., E. Sieliwonczyk, D.P.O., J.S.W.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libor","family":"Pastika","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-0118","authenticated-orcid":true,"given":"Nikesh","family":"Bajaj","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9228-2518","authenticated-orcid":true,"given":"Mehak","family":"Gurnani","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-7044","authenticated-orcid":true,"given":"Ewa","family":"Sieliwonczyk","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."},{"name":"Medical Research Council Laboratory of Medical Sciences (K.A.M., E. Sieliwonczyk, D.P.O., J.S.W.), Imperial College London, United Kingdom."},{"name":"Faculty of Medicine and Health Sciences, Center for Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium (E. Sieliwonczyk)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-8490","authenticated-orcid":true,"given":"Konstantinos","family":"Patlatzoglou","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2654-8117","authenticated-orcid":true,"given":"Maddalena","family":"Ardissino","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-8282","authenticated-orcid":true,"given":"Jun Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1809-9729","authenticated-orcid":true,"given":"Huiyi","family":"Wu","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xili","family":"Shi","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0159-1610","authenticated-orcid":true,"given":"Katerina","family":"Hnatkova","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean L.","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. 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Sabino)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-2460","authenticated-orcid":true,"given":"Luana","family":"Giatti","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, and Hospital das Cl\u00ednicas\/Empresa Brasileira de Servi\u00e7os Hospitalares (L.G., S.M.B.), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7383-7811","authenticated-orcid":true,"given":"Sandhi M.","family":"Barreto","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Medicine, and Hospital das Cl\u00ednicas\/Empresa Brasileira de Servi\u00e7os Hospitalares (L.G., S.M.B.), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-5638","authenticated-orcid":true,"given":"Jonathan W.","family":"Waks","sequence":"additional","affiliation":[{"name":"Harvard-Thorndike Electrophysiology Institute (J.W.W.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4241-3586","authenticated-orcid":true,"given":"Daniel B.","family":"Kramer","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. Sieliwonczyk, K.P., M.A., J.Y.C., H.W., X.S., K.H., S.Z., D.B.K., N.S.P., M.M., J.S.W., F.S.N.), Imperial College London, United Kingdom."},{"name":"Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology (D.B.K.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Mandic","sequence":"additional","affiliation":[{"name":"Department of Electrical and Electronic Engineering (D.M.), Imperial College London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-8078","authenticated-orcid":true,"given":"Nicholas S.","family":"Peters","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute (A.S., K.A.M., L.P., N.B., M.G., E. 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