{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T03:28:51Z","timestamp":1794281331758,"version":"4.9.0"},"reference-count":42,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018609","name":"High-level Hospital Construction Project of Guangdong Provincial People&apos;s Hospital","doi-asserted-by":"publisher","award":["LCZX202404"],"award-info":[{"award-number":["LCZX202404"]}],"id":[{"id":"10.13039\/501100018609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2024NSCQ-MSX0007"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX0007"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470325"],"award-info":[{"award-number":["82470325"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200352"],"award-info":[{"award-number":["82200352"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300352"],"award-info":[{"award-number":["82300352"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370322"],"award-info":[{"award-number":["82370322"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000320"],"award-info":[{"award-number":["82000320"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20230733"],"award-info":[{"award-number":["BK20230733"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","heartrhythmopen.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Heart Rhythm O2"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.hroo.2025.12.022","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:33:15Z","timestamp":1767918795000},"page":"522-534","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Personalized in vitro models reveal functional impact of a KCNH2 mutation and enable drug screening in LQTS2"],"prefix":"10.1016","volume":"7","author":[{"given":"Bingyu","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzun","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangwei","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9844-486X","authenticated-orcid":false,"given":"Minglong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.hroo.2025.12.022_bib1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.jacep.2022.02.017","article-title":"Congenital long QT syndrome","volume":"8","author":"Krahn","year":"2022","journal-title":"JACC Clin Electrophysiol"},{"key":"10.1016\/j.hroo.2025.12.022_bib2","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ejphar.2014.06.044","article-title":"hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia","volume":"741","author":"Nogawa","year":"2014","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.hroo.2025.12.022_bib3","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1161\/CIRCRESAHA.116.304030","article-title":"Genetics of sudden cardiac death","volume":"116","author":"Bezzina","year":"2015","journal-title":"Circ Res"},{"key":"10.1016\/j.hroo.2025.12.022_bib4","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/heartjnl-2020-318259","article-title":"Diagnosis, management and therapeutic strategies for congenital long QT syndrome","volume":"108","author":"Wilde","year":"2022","journal-title":"Heart"},{"key":"10.1016\/j.hroo.2025.12.022_bib5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000440608","article-title":"Common genotypes of long QT syndrome in China and the role of ECG prediction","volume":"133","author":"Gao","year":"2016","journal-title":"Cardiology"},{"key":"10.1016\/j.hroo.2025.12.022_bib6","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1152\/physrev.00002.2005","article-title":"Molecular physiology of cardiac repolarization","volume":"85","author":"Nerbonne","year":"2005","journal-title":"Physiol Rev"},{"key":"10.1016\/j.hroo.2025.12.022_bib7","doi-asserted-by":"crossref","first-page":"9235","DOI":"10.3390\/ijms22179235","article-title":"H1153Y-KCNH2 mutation identified in a sudden arrhythmic death syndrome case alters channel gating","volume":"22","author":"Farrugia","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.hroo.2025.12.022_bib8","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1161\/01.CIR.101.6.616","article-title":"Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome","volume":"101","author":"Moss","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.hroo.2025.12.022_bib9","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1161\/01.CIR.0000125523.14403.1E","article-title":"Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome","volume":"109","author":"Schwartz","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.hroo.2025.12.022_bib10","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.016398","article-title":"Outcome by sex in patients with long QT syndrome with an implantable cardioverter defibrillator","volume":"9","author":"Younis","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.hroo.2025.12.022_bib11","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41569-019-0179-0","article-title":"Animal models of arrhythmia: classic electrophysiology to genetically modified large animals","volume":"16","author":"Clauss","year":"2019","journal-title":"Nat Rev Cardiol"},{"key":"10.1016\/j.hroo.2025.12.022_bib12","article-title":"Continuous contractile force and electrical signal recordings of 3D cardiac tissue utilizing conductive hydrogel pillars on a chip","volume":"20","author":"Zhang","year":"2023","journal-title":"Mater Today Bio"},{"key":"10.1016\/j.hroo.2025.12.022_bib13","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.609","article-title":"A standardised hERG phenotyping pipeline to evaluate KCNH2 genetic variant pathogenicity","volume":"11","author":"Oliveira-Mendes","year":"2021","journal-title":"Clin Transl Med"},{"key":"10.1016\/j.hroo.2025.12.022_bib14","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1038\/ncomms6535","article-title":"Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome","volume":"5","author":"Anderson","year":"2014","journal-title":"Nat Commun"},{"key":"10.1016\/j.hroo.2025.12.022_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.107526","article-title":"Rescue of expression and function of long QT syndrome-causing mutant hERG channels by enhancing channel stability in the plasma membrane","volume":"300","author":"Davis","year":"2024","journal-title":"J Biol Chem"},{"key":"10.1016\/j.hroo.2025.12.022_bib16","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.yjmcc.2018.01.009","article-title":"Restoration of mutant hERG stability by inhibition of HDAC6","volume":"115","author":"Li","year":"2018","journal-title":"J Mol Cell Cardiol"},{"key":"10.1016\/j.hroo.2025.12.022_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2022.166487","article-title":"Deacetylation mechanism and potential reversal strategy of long QT syndrome on hERG K+ channel under hypoxia","volume":"1868","author":"Xue","year":"2022","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"10.1016\/j.hroo.2025.12.022_bib18","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/cvr\/cvu060","article-title":"Re-trafficking of hERG reverses long QT syndrome 2 phenotype in human iPS-derived cardiomyocytes","volume":"102","author":"Mehta","year":"2014","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.hroo.2025.12.022_bib19","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCEP.120.009343","article-title":"Long QT syndrome KCNH2 variant induces hERG1a\/1b subunit imbalance in patient-specific induced pluripotent stem cell\u2013derived cardiomyocytes","volume":"14","author":"Feng","year":"2021","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"10.1016\/j.hroo.2025.12.022_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.107465","article-title":"The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel KV11.1 associated with long QT syndrome","volume":"300","author":"Egly","year":"2024","journal-title":"J Biol Chem"},{"key":"10.1016\/j.hroo.2025.12.022_bib21","article-title":"ML277 specifically enhances the fully activated open state of KCNQ1 by modulating VSD-pore coupling","volume":"8","author":"Hou","year":"2019","journal-title":"Elfie"},{"key":"10.1016\/j.hroo.2025.12.022_bib22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ejphar.2010.10.016","article-title":"Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with long-QT syndrome 1 both in vitro and in vivo","volume":"650","author":"Biermann","year":"2011","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.hroo.2025.12.022_bib23","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.hrthm.2009.05.021","article-title":"Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test","volume":"6","author":"Kapplinger","year":"2009","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hroo.2025.12.022_bib24","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1161\/01.RES.0000128561.28701.ea","article-title":"Biology of cardiac arrhythmias: ion channel protein trafficking","volume":"94","author":"Delisle","year":"2004","journal-title":"Circ Res"},{"key":"10.1016\/j.hroo.2025.12.022_bib25","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/toxsci\/kfw200","article-title":"Comprehensive translational assessment of human-induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias","volume":"155","author":"Blinova","year":"2017","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.hroo.2025.12.022_bib26","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/s41598-021-04659-w","article-title":"Thyroid hormones regulate cardiac repolarization and QT-interval related gene expression in hiPSC cardiomyocytes","volume":"12","author":"Ulivieri","year":"2022","journal-title":"Sci Rep"},{"key":"10.1016\/j.hroo.2025.12.022_bib27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13287-017-0566-6","article-title":"Structural and electrophysiological dysfunctions due to increased endoplasmic reticulum stress in a long-term pacing model using human induced pluripotent stem cell-derived ventricular cardiomyocytes","volume":"8","author":"Cui","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"10.1016\/j.hroo.2025.12.022_bib28","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.stemcr.2020.10.005","article-title":"Isogenic sets of hiPSC-CMs harboring distinct KCNH2 mutations differ functionally and in susceptibility to drug-induced arrhythmias","volume":"15","author":"Brand\u00e3o","year":"2020","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.hroo.2025.12.022_bib29","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2025.1524909","article-title":"Pathogenic KCNH2-G53S variant in the PAS domain influences the electrophysiological phenotype in long QT syndrome type 2","volume":"12","author":"Mun","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"10.1016\/j.hroo.2025.12.022_bib30","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jacc.2014.04.057","article-title":"Genome editing of isogenic human induced pluripotent stem cells recapitulates long QT phenotype for drug testing","volume":"64","author":"Wang","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.hroo.2025.12.022_bib31","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.3390\/cells9051153","article-title":"hiPSC-derived cardiomyocyte model of LQT2 syndrome derived from asymptomatic and symptomatic mutation carriers reproduces clinical differences in aggregates but not in single cells","volume":"9","author":"Shah","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.hroo.2025.12.022_bib32","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.hrthm.2020.08.017","article-title":"Long QT syndrome type 1 and 2 patients respond differently to arrhythmic triggers: the TriQarr in vivo study","volume":"18","author":"Marstrand","year":"2021","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hroo.2025.12.022_bib33","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/cvr\/cvac103","article-title":"Initiation of ventricular arrhythmia in the acquired long QT syndrome","volume":"119","author":"Alexander","year":"2023","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.hroo.2025.12.022_bib34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1631\/bdm.2400168","article-title":"Deep phenotyping of testosterone-prompted fibrosis in arrhythmogenic right ventricular cardiomyopathy using iPSC-derived engineered cardiac spheroids","volume":"8","author":"Cheng","year":"2025","journal-title":"Bio-des Manuf"},{"key":"10.1016\/j.hroo.2025.12.022_bib35","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abq6720","article-title":"Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues","volume":"8","author":"Veldhuizen","year":"2022","journal-title":"Sci Adv"},{"key":"10.1016\/j.hroo.2025.12.022_bib36","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.jacc.2014.05.068","article-title":"Efficacy of different beta-blockers in the treatment of long QT syndrome","volume":"64","author":"Abu-Zeitone","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.hroo.2025.12.022_bib37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/CIRCULATIONAHA.105.570200","article-title":"Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism","volume":"113","author":"Anderson","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.hroo.2025.12.022_bib38","doi-asserted-by":"crossref","first-page":"35749","DOI":"10.1074\/jbc.M305787200","article-title":"Thapsigargin selectively rescues the trafficking defective LQT2 channels G601S and F805C","volume":"278","author":"Delisle","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1016\/j.hroo.2025.12.022_bib39","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1161\/01.CIR.97.16.1581","article-title":"Improvement of repolarization abnormalities by a K+ channel opener in the LQT1 form of congenital long-QT syndrome","volume":"97","author":"Shimizu","year":"1998","journal-title":"Circulation"},{"key":"10.1016\/j.hroo.2025.12.022_bib40","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1161\/CIRCULATIONAHA.107.758672","article-title":"Feedback remodeling of cardiac potassium current expression: a novel potential mechanism for control of repolarization reserve","volume":"118","author":"Xiao","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.hroo.2025.12.022_bib41","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1093\/cvr\/cvae042","article-title":"The electrophysiologic effects of KCNQ1 extend beyond expression of IKs: evidence from genetic and pharmacologic block","volume":"120","author":"Wada","year":"2024","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.hroo.2025.12.022_bib42","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1016\/j.jacc.2020.02.067","article-title":"KCNQ1 antibodies for immunotherapy of long QT syndrome type 2","volume":"75","author":"Maguy","year":"2020","journal-title":"J Am Coll Cardiol"}],"container-title":["Heart Rhythm O2"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666501826000097?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666501826000097?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:16:31Z","timestamp":1777637791000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666501826000097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S2666501826000097"],"URL":"https:\/\/doi.org\/10.1016\/j.hroo.2025.12.022","relation":{},"ISSN":["2666-5018"],"issn-type":[{"value":"2666-5018","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Personalized in vitro models reveal functional impact of a KCNH2 mutation and enable drug screening in LQTS2","name":"articletitle","label":"Article Title"},{"value":"Heart Rhythm O2","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.hroo.2025.12.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Heart Rhythm Society. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}