{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:38:36Z","timestamp":1784875116563,"version":"3.55.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000098","name":"Stem Cell Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada Research Chair"},{"name":"Michael Smith Foundation"},{"DOI":"10.13039\/100010658","name":"St. Paul's Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010658","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Stem Cell Reports"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1016\/j.stemcr.2019.03.011","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T10:34:18Z","timestamp":1556188458000},"page":"996-1006","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":51,"title":["Ibrutinib Displays Atrial-Specific Toxicity in Human Stem Cell-Derived Cardiomyocytes"],"prefix":"10.1016","volume":"12","author":[{"given":"Sanam","family":"Shafaattalab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Effimia","family":"Christidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Nartiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Analucia","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeehon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Protze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Brunham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen F.","family":"Tibbits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Laksman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.stemcr.2019.03.011_bib1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.pbiomolbio.2012.07.012","article-title":"Electrophysiological and contractile function of cardiomyocytes derived from human embryonic stem cells","volume":"110","author":"Blazeski","year":"2012","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib2","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.3324\/haematol.2017.171041","article-title":"Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials","volume":"102","author":"Brown","year":"2017","journal-title":"Haematologica"},{"key":"10.1016\/j.stemcr.2019.03.011_bib3","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia","volume":"373","author":"Burger","year":"2015","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.stemcr.2019.03.011_bib4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1509981","article-title":"Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia","volume":"374","author":"Byrd","year":"2016","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.stemcr.2019.03.011_bib5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.vascn.2016.06.002","article-title":"The comprehensive in\u00a0vitro proarrhythmia assay (CiPA) initiative\u2014update on progress","volume":"81","author":"Colatsky","year":"2016","journal-title":"J.\u00a0Pharmacol. Toxicol. Methods"},{"key":"10.1016\/j.stemcr.2019.03.011_bib6","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s00280-017-3471-x","article-title":"Ibrutinib does not prolong the corrected QT interval in healthy subjects: results from a thorough QT study","volume":"80","author":"de Jong","year":"2017","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib7","doi-asserted-by":"crossref","first-page":"394","DOI":"10.15252\/emmm.201404757","article-title":"Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology","volume":"7","author":"Devalla","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.stemcr.2019.03.011_bib8","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/nbt.2005","article-title":"SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells","volume":"29","author":"Dubois","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib9","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/nmeth.1740","article-title":"NKX2-5(eGFP\/w) hESCs for isolation of human cardiac progenitors and cardiomyocytes","volume":"8","author":"Elliott","year":"2011","journal-title":"Nat. Methods"},{"key":"10.1016\/j.stemcr.2019.03.011_bib10","doi-asserted-by":"crossref","first-page":"13742","DOI":"10.1073\/pnas.1002077107","article-title":"Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells","volume":"107","author":"Evseenko","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.stemcr.2019.03.011_bib11","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.hrthm.2006.12.047","article-title":"Application of blebbistatin as an excitation-contraction uncoupler for electrophysiologic study of rat and rabbit hearts","volume":"4","author":"Fedorov","year":"2007","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.stemcr.2019.03.011_bib12","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1161\/CIRCULATIONAHA.106.656504","article-title":"Mechanism underlying initiation of paroxysmal atrial flutter\/atrial fibrillation by ectopic foci: a simulation study","volume":"115","author":"Gong","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.stemcr.2019.03.011_bib13","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1161\/CIRCRESAHA.111.247494","article-title":"Optical imaging of voltage and calcium in cardiac cells & tissues","volume":"110","author":"Herron","year":"2012","journal-title":"Circ. Res."},{"key":"10.1016\/j.stemcr.2019.03.011_bib14","doi-asserted-by":"crossref","first-page":"13075","DOI":"10.1073\/pnas.1004594107","article-title":"The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy","volume":"107","author":"Honigberg","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.stemcr.2019.03.011_bib15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/bjh.12895","article-title":"Breaking good: the inexorable rise of BTK inhibitors in the treatment of chronic lymphocytic leukaemia","volume":"166","author":"Hutchinson","year":"2014","journal-title":"Br. J. Haematol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib16","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1161\/CIRCULATIONAHA.111.019893","article-title":"Atrial fibrillation pathophysiology: implications for management","volume":"124","author":"Iwasaki","year":"2011","journal-title":"Circulation"},{"key":"10.1016\/j.stemcr.2019.03.011_bib17","first-page":"1008","article-title":"The next generation of targeted molecules for the treatment of chronic lymphocytic leukemia","volume":"30","author":"Jeyakumar","year":"2016","journal-title":"Oncology (Williston Park)"},{"key":"10.1016\/j.stemcr.2019.03.011_bib18","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1046\/j.1440-169X.1997.t01-5-00009.x","article-title":"Expressions of PDGF receptor alpha, c-Kit and Flk1 genes clustering in mouse chromosome 5 define distinct subsets of nascent mesodermal cells","volume":"39","author":"Kataoka","year":"1997","journal-title":"Dev. Growth Differ."},{"key":"10.1016\/j.stemcr.2019.03.011_bib19","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.stem.2010.12.008","article-title":"Stage-specific optimization of activin\/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines","volume":"8","author":"Kattman","year":"2011","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stemcr.2019.03.011_bib20","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature11799","article-title":"Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs","volume":"494","author":"Kim","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.stemcr.2019.03.011_bib21","doi-asserted-by":"crossref","first-page":"5268","DOI":"10.1038\/s41598-017-05652-y","article-title":"Modeling atrial fibrillation using human embryonic stem cell-derived atrial tissue","volume":"7","author":"Laksman","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.stemcr.2019.03.011_bib22","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.stem.2012.10.010","article-title":"Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells","volume":"12","author":"Lan","year":"2013","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stemcr.2019.03.011_bib23","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1111\/j.1530-0277.2009.01006.x","article-title":"Alcohol-induced electrical remodeling: effects of sustained short-term ethanol infusion on ion currents in rabbit atrium","volume":"33","author":"Laszlo","year":"2009","journal-title":"Alcohol Clin. Exp. Res."},{"key":"10.1016\/j.stemcr.2019.03.011_bib24","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.3109\/10428194.2016.1169408","article-title":"Ibrutinib-related atrial fibrillation in patients with mantle cell lymphoma","volume":"57","author":"Lee","year":"2016","journal-title":"Leuk. Lymphoma"},{"key":"10.1016\/j.stemcr.2019.03.011_bib25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.stem.2017.07.003","article-title":"Human pluripotent stem cell-derived atrial and ventricular cardiomyocytes develop from distinct mesoderm populations","volume":"21","author":"Lee","year":"2017","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stemcr.2019.03.011_bib26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1182\/blood-2016-05-712828","article-title":"The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis","volume":"128","author":"Leong","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.03.011_bib27","doi-asserted-by":"crossref","first-page":"R755","DOI":"10.1152\/ajpregu.00001.2015","article-title":"Construction and use of a zebrafish heart voltage and calcium optical mapping system, with integrated electrocardiogram and programmable electrical stimulation","volume":"308","author":"Lin","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib28","doi-asserted-by":"crossref","first-page":"R823","DOI":"10.1152\/ajpregu.00002.2014","article-title":"Optical mapping of the electrical activity of isolated adult zebrafish hearts: acute effects of temperature","volume":"306","author":"Lin","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib29","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1182\/blood-2014-10-604272","article-title":"Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling","volume":"124","author":"McMullen","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.03.011_bib30","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa0908679","article-title":"Patient-specific induced pluripotent stem-cell models for long-QT syndrome","volume":"363","author":"Moretti","year":"2010","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.stemcr.2019.03.011_bib31","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1161\/01.CIR.0000037062.35762.B4","article-title":"Alternans of atrial action potentials during atrial flutter as a precursor to atrial fibrillation","volume":"106","author":"Narayan","year":"2002","journal-title":"Circulation"},{"key":"10.1016\/j.stemcr.2019.03.011_bib32","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nprot.2008.42","article-title":"A protocol describing the use of a recombinant protein-based, animal product-free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies","volume":"3","author":"Ng","year":"2008","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.stemcr.2019.03.011_bib33","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1158\/1078-0432.CCR-16-1446","article-title":"Comparison of acalabrutinib, a selective Bruton tyrosine kinase inhibitor, with ibrutinib in\u00a0chronic lymphocytic leukemia cells","volume":"23","author":"Patel","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.stemcr.2019.03.011_bib34","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cell.2007.01.042","article-title":"An Nkx2-5\/Bmp2\/Smad1 negative feedback loop controls heart progenitor specification and proliferation","volume":"128","author":"Prall","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.stemcr.2019.03.011_bib35","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaf2584","article-title":"High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells","volume":"9","author":"Sharma","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.stemcr.2019.03.011_bib36","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.hrthm.2010.06.021","article-title":"Alteration of tyrosine kinase signaling: another player in the arrhythmogenesis of atrial fibrillation?","volume":"7","author":"Shinlapawittayatorn","year":"2010","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.stemcr.2019.03.011_bib37","doi-asserted-by":"crossref","first-page":"130ra147","DOI":"10.1126\/scitranslmed.3003552","article-title":"Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy","volume":"4","author":"Sun","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.stemcr.2019.03.011_bib38","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/10428194.2017.1339874","article-title":"Atrial fibrillation as a complication of ibrutinib therapy: clinical features and challenges of management","volume":"59","author":"Thorp","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"10.1016\/j.stemcr.2019.03.011_bib39","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1501548","article-title":"Ibrutinib in previously treated Waldenstrom's macroglobulinemia","volume":"372","author":"Treon","year":"2015","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.stemcr.2019.03.011_bib40","first-page":"3231","article-title":"Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells","volume":"142","author":"van den Berg","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.stemcr.2019.03.011_bib41","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1182\/blood-2013-09-527853","article-title":"Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy","volume":"123","author":"Woyach","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.03.011_bib42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13045-016-0250-9","article-title":"Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor","volume":"9","author":"Wu","year":"2016","journal-title":"J.\u00a0Hematol. Oncol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib43","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1002\/stem.2070","article-title":"Concise review: cardiac disease modeling using induced pluripotent stem cells","volume":"33","author":"Yang","year":"2015","journal-title":"Stem Cells"},{"key":"10.1016\/j.stemcr.2019.03.011_bib44","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1016\/j.jacc.2009.02.050","article-title":"Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management","volume":"53","author":"Yeh","year":"2009","journal-title":"J.\u00a0Am. Coll. Cardiol."},{"key":"10.1016\/j.stemcr.2019.03.011_bib45","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/cr.2010.163","article-title":"Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals","volume":"21","author":"Zhang","year":"2011","journal-title":"Cell Res."},{"key":"10.1016\/j.stemcr.2019.03.011_bib46","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1161\/CIRCEP.113.000502","article-title":"Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats","volume":"6","author":"Zhang","year":"2013","journal-title":"Circ. Arrhythmia Electrophysiol."}],"container-title":["Stem Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671119300967?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671119300967?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:41:34Z","timestamp":1761990094000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213671119300967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["S2213671119300967"],"URL":"https:\/\/doi.org\/10.1016\/j.stemcr.2019.03.011","relation":{},"ISSN":["2213-6711"],"issn-type":[{"value":"2213-6711","type":"print"}],"subject":[],"published":{"date-parts":[[2019,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ibrutinib Displays Atrial-Specific Toxicity in Human Stem Cell-Derived Cardiomyocytes","name":"articletitle","label":"Article Title"},{"value":"Stem Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.stemcr.2019.03.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors.","name":"copyright","label":"Copyright"}]}}