{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:00:27Z","timestamp":1784545227852,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001220","name":"Medical Advances Without Animals Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["app1182032"],"award-info":[{"award-number":["app1182032"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["app1182623"],"award-info":[{"award-number":["app1182623"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001220","name":"Medical Advances Without Animals Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background and Purpose:<\/jats:bold>\n                    Torsades de pointes is a potentially lethal ventricular arrhythmia that can be induced by many classes of drugs. The risk for a given drug depends upon the combination of cardiac ion channels that it targets. The axis of arrhythmia quantifies that risk. It is a conceptual line in the electrophysiology that describes the most potent combination of ion channel blocks that is theoretically possible. The axis thus serves as a convenient yardstick for quantifying the pro\u2010arrhythmic risk of real drugs. Until now, the axis of arrhythmia has only been derived from biophysical computer simulations.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Experimental Approach:<\/jats:bold>\n                    Here, we derive the axis directly from the response profiles of four key cardiac ion currents \n and \n using publicly available drug datasets. The new method provides an independent line of evidence for the axis of arrhythmia.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Key Results:<\/jats:bold>\n                    Following a process of step\u2010wise reduction, the two methods were found to converge to identical estimates of the axis in two ion currents \n and \n. The final estimate of the axis predicted the pro\u2010arrhythmic risk of the drugs (n=109) with 89.9% to 91.7% accuracy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion and Implications:<\/jats:bold>\n                    The axis of arrhythmia offers a practical method for predicting the pro\u2010arrhythmic risk of novel drugs prior to clinical trials, without the need for drug\u2010specific computer simulations. It is the only metric of pro\u2010arrhythmic risk that has been derived from both a biophysical model and a statistical model. It thus combines the benefits of biophysical interpretation and computational efficiency when assessing torsadogenic risk.\n                  <\/jats:p>","DOI":"10.1111\/bph.70078","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T22:42:17Z","timestamp":1748817737000},"page":"4299-4313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Independent derivations of the axis of arrhythmia for predicting drug\u2010induced torsades de pointes"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-9514","authenticated-orcid":false,"given":"Stewart","family":"Heitmann","sequence":"first","affiliation":[{"name":"Victor Chang Cardiac Research Institute  Darlinghurst NSW Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health UNSW Sydney  Kensington NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-3716","authenticated-orcid":false,"given":"Jamie I.","family":"Vandenberg","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute  Darlinghurst NSW Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health UNSW Sydney  Kensington NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6403-1282","authenticated-orcid":false,"given":"Adam P.","family":"Hill","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute  Darlinghurst NSW Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health UNSW Sydney  Kensington NSW Australia"},{"name":"Victor Chang Cardiac Research Institute Innovation Centre  Darlinghurst NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17081091"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.09.069"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa280"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2016.06.002"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01237.2009"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057115594589"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neucom.2018.06.026"},{"key":"e_1_2_12_10_1","volume-title":"Handbook for the brain dynamics toolbox: Version 2022","author":"Heitmann S.","year":"2022"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.90027.3"},{"key":"e_1_2_12_12_1","first-page":"iv","article-title":"The possible effects of the aggregation of the molecules of hemoglobin on its dissociation curves","volume":"40","author":"Hill A. 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