{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:25:19Z","timestamp":1777425919473,"version":"3.51.4"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0204712","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T13:24:36Z","timestamp":1562592276000},"page":"e0204712","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["T vector velocity: A new ECG biomarker for identifying drug effects on cardiac ventricular repolarization"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-729X","authenticated-orcid":true,"given":"Werner","family":"Bystricky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Maier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Gintant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6484-1974","authenticated-orcid":true,"given":"Dennis","family":"Bergau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kent","family":"Kamradt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2459-4873","authenticated-orcid":true,"given":"Patrick","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8102-7795","authenticated-orcid":true,"given":"David","family":"Carter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,7,8]]},"reference":[{"key":"ref1","unstructured":"ICH. The clinical evaluation of qt\/qtc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs; 2005. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Efficacy\/E14\/E14_Guideline.pdf\" xlink:type=\"simple\">http:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Efficacy\/E14\/E14_Guideline.pdf<\/ext-link>."},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1098\/rsta.2008.0284","article-title":"Measurement and regulation of cardiac ventricular repolarization: from the QT interval to repolarization morphology","volume":"367","author":"JP Couderc","year":"2009","journal-title":"Philosophical Transactions Series A, Mathematical, Physical, and Engineering Sciences"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.bspc.2011.05.010","article-title":"Review of T-wave morphology-based biomarkers of ventricular repolarisation using the surface electrocardiogram","volume":"7","author":"TP Brennan","year":"2012","journal-title":"Biomedical Signal Processing and Control"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.jelectrocard.2008.07.016","article-title":"T(p-e)\/QT ratio as an index of arrhythmogenesis","volume":"41","author":"P Gupta","year":"2008","journal-title":"Journal of Electrocardiology"},{"key":"ref5","unstructured":"Jie X, Rodriguez B, Pueyo E. A new ECG biomarker for drug toxicity: A combined signal processing and computational modeling study. In: Proc. Annual Int. Conf. of the IEEE Engineering in Medicine and Biology; 2010. p. 2565\u20132568."},{"key":"ref6","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1007\/BF02513351","article-title":"Spatial, temporal and wavefront direction characteristics of 12-lead T-wave morphology","volume":"37","author":"B Acar","year":"1999","journal-title":"Medical & Biological Engineering & Computing"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.hrthm.2006.05.025","article-title":"Elucidation of the spatial ventricular gradient and its link with dispersion of repolarization","volume":"3","author":"HHM Draisma","year":"2006","journal-title":"Heart Rhythm"},{"key":"ref8","first-page":"249","article-title":"Improving the detection of subtle I(Kr)-inhibition: assessing electrocardiographic abnormalities of repolarization induced by moxifloxacin","volume":"31","author":"JP Couderc","year":"2008","journal-title":"Drug Safety"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Andersen MP, Xue JQ, Graff C, Hardahl TB, Toft E, Kanters JK, et al. A robust method for quantification of IKr-related T-wave morphology abnormalities. In: Proc. Computers in Cardiology; 2007. p. 341\u2013344.","DOI":"10.1109\/CIC.2007.4745491"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2165\/00002018-200932070-00006","article-title":"Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology","volume":"32","author":"C Graff","year":"2009","journal-title":"Drug Safety"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"613","DOI":"10.2165\/00002018-200932070-00007","article-title":"Drug-induced changes in the T-wave morphology","volume":"32","author":"M Malik","year":"2009","journal-title":"Drug Safety"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ahj.2013.11.004","article-title":"Rechanneling the cardiac proarrhythmia safety paradigm: a meeting report from the Cardiac Safety Research Consortium","volume":"167","author":"PT Sager","year":"2014","journal-title":"American Heart Journal"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/clpt.2014.155","article-title":"Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil","volume":"96","author":"L Johannesen","year":"2014","journal-title":"Clinical Pharmacology and Therapeutics"},{"key":"ref14","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.114.001615","article-title":"Comprehensive T wave morphology assessment in a randomized clinical study of dofetilide, quinidine, ranolazine, and verapamil","volume":"4","author":"J Vicente","year":"2015","journal-title":"Journal of the American Heart Association"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/cpt.205","article-title":"Late sodium current block for drug-induced long QT syndrome: Results from a prospective clinical trial","volume":"99","author":"L Johannesen","year":"2016","journal-title":"Clinical Pharmacology and Therapeutics"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"e0163619","DOI":"10.1371\/journal.pone.0163619","article-title":"Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block","volume":"11","author":"J Vicente","year":"2016","journal-title":"PloS one"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.vascn.2016.06.002","article-title":"The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative\u2014Update on progress","volume":"81","author":"T Colatsky","year":"2016","journal-title":"Journal of pharmacological and toxicological methods"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.jelectrocard.2017.07.010","article-title":"Automated JTpeak analysis by BRAVO","volume":"50","author":"F Badilini","year":"2017","journal-title":"Journal of electrocardiology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"E215","DOI":"10.1161\/01.CIR.101.23.e215","article-title":"PhysioBank, PhysioToolkit, and PhysioNet: components of a new research resource for complex physiologic signals","volume":"101","author":"AL Goldberger","year":"2000","journal-title":"Circulation"},{"key":"ref20","unstructured":"ECGRDVQ. ECG Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects; 2016. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.physionet.org\/physiobank\/database\/ecgrdvq\/\" xlink:type=\"simple\">https:\/\/www.physionet.org\/physiobank\/database\/ecgrdvq\/<\/ext-link>."},{"key":"ref21","unstructured":"ECGDMMLD. ECG effects of Dofetilide, Moxifloxacin, Dofetilide+Mexiletine, Dofetilide+Lidocaine and Moxifloxacin+Diltiazem in Healthy Subjects; 2016. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.physionet.org\/physiobank\/database\/ecgdmmld\/\" xlink:type=\"simple\">https:\/\/www.physionet.org\/physiobank\/database\/ecgdmmld\/<\/ext-link>."},{"key":"ref22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1046\/j.1542-474X.2003.08413.x","article-title":"The duration of systole in an electrocardiogram in normal humans and in patients with heart disease. 1920","volume":"8","author":"LS Fridericia","year":"2003","journal-title":"Annals of Noninvasive Electrocardiology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0010-4809(77)90021-0","article-title":"Electrocardiogram baseline noise estimation and removal using cubic splines and state-space computation techniques","volume":"10","author":"CR Meyer","year":"1977","journal-title":"Computers and biomedical research, an international journal"},{"key":"ref24","article-title":"R: A Language and Environment for Statistical Computing","year":"2017"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/clc.1980.3.2.87","article-title":"On deriving the electrocardiogram from vectoradiographic leads","volume":"3","author":"GE Dower","year":"1980","journal-title":"Clinical Cardiology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e1002061","DOI":"10.1371\/journal.pcbi.1002061","article-title":"Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation","volume":"7","author":"T O\u2019Hara","year":"2011","journal-title":"PLoS Computational Biology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/cpt.896","article-title":"Mechanistic Model-Informed Proarrhythmic Risk Assessment of Drugs: Review of the &quot;CiPA&quot; Initiative and Design of a Prospective Clinical Validation Study","volume":"103","author":"J Vicente","year":"2018","journal-title":"Clinical Pharmacology and Therapeutics"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s40261-015-0328-0","article-title":"The T-peak-T-end interval as a marker of repolarization abnormality: a comparison with the QT interval for five different drugs","volume":"35","author":"TA Bhuiyan","year":"2015","journal-title":"Clinical Drug Investigation"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.jelectrocard.2017.07.019","article-title":"JT interval: What does this interval mean?","volume":"50","author":"W Zareba","year":"2017","journal-title":"Journal of Electrocardiology"},{"key":"ref30","article-title":"Challenges in implementing and obtaining acceptance for J-Tpeak assessment as the clinical component of CiPA","author":"B Darpo","year":"2018","journal-title":"Journal of Pharmacological and Toxicological Methods"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/cpt.1303","article-title":"Assessment of Multi-Ion Channel Block in a Phase I Randomized Study Design: Results of the CiPA Phase I ECG Biomarker Validation Study","volume":"105","author":"J Vicente","year":"2019","journal-title":"Clinical pharmacology and therapeutics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0204712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T11:28:53Z","timestamp":1589023733000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0204712"}},"subtitle":[],"editor":[{"given":"Randall Lee","family":"Rasmusson","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,7,8]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0204712","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/418277","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,8]]}}}