{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T10:52:20Z","timestamp":1773485540953,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Although prior studies indicate that a QTc\u2009&gt;\u2009500\u2009ms on a single baseline 12\u2010lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective analysis of 433 patients with LQTS evaluated, risk\u2010stratified, and undergoing active guideline\u2010based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope\/seizure, sudden cardiac arrest (SCA), appropriate VF\u2010terminating ICD shock, and sudden cardiac death (SCD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During the median follow\u2010up of 5.5 years (interquartile range [IQR]\u2009=\u20093\u20139), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520\u2009ms and median QTc threshold of 490\u2009ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c\u2010statistic\u2009=\u20090.93\u20130.95). Patients in the high\u2010risk group (median QTc\u2009&gt;\u2009490\u2009ms and maximum QTc\u2009&gt;\u2009520\u2009ms) had a significantly lower BCE free survival (70%\u201381%) when compared to patients in both medium\u2010risk (93%\u201397%) and low\u2010risk (98%\u201399%) groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc\u2009&gt;\u2009520\u2009ms and median QTc\u2009&gt;\u2009490\u2009ms over serial 12\u2010lead ECGs are at the highest risk of BCE while on guideline\u2010directed medical therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.16293","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T05:19:40Z","timestamp":1715318380000},"page":"1370-1381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Utilizing median and maximum QTc values improves prediction of breakthrough cardiac events in pediatric long QT syndrome"],"prefix":"10.1111","volume":"35","author":[{"given":"Ram K.","family":"Rohatgi","sequence":"first","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine\/Division of Pediatric Cardiology\/Windland Smith Rice Genetic Heart Rhythm Clinic Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9181-1970","authenticated-orcid":false,"given":"Andrew S.","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine\/Division of Heart Rhythm Services Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-6968","authenticated-orcid":false,"given":"Alan M.","family":"Sugrue","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine\/Division of Heart Rhythm Services Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander T.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research\/Division of Biomedical Statistics and Informatics Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher G.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research\/Division of Biomedical Statistics and Informatics Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4560-2753","authenticated-orcid":false,"given":"Phillip L.","family":"Wackel","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine\/Division of Pediatric Cardiology\/Windland Smith Rice Genetic Heart Rhythm Clinic Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan C.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine\/Division of Pediatric Cardiology\/Windland Smith Rice Genetic Heart Rhythm Clinic Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Martijn","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine\/Division of Pediatric Cardiology\/Windland Smith Rice Genetic Heart Rhythm Clinic Mayo Clinic Rochester Minnesota USA"},{"name":"Department of Cardiovascular Medicine\/Division of Heart Rhythm Services Mayo Clinic Rochester Minnesota USA"},{"name":"Department of Molecular Pharmacology &amp; Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-3333","authenticated-orcid":false,"given":"Michael J.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine\/Division of Pediatric Cardiology\/Windland Smith Rice Genetic Heart Rhythm Clinic Mayo Clinic Rochester Minnesota USA"},{"name":"Department of Cardiovascular Medicine\/Division of Heart Rhythm Services Mayo Clinic Rochester Minnesota USA"},{"name":"Department of Molecular Pharmacology &amp; Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht089"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(57)90079-0"},{"key":"e_1_2_8_4_1","first-page":"103","article-title":"A new familial cardiac syndrome in children","volume":"54","author":"Ward OC","year":"1964","journal-title":"J Ir Med Assoc"},{"key":"e_1_2_8_5_1","article-title":"An analysis of the time relations of electrocardiograms","volume":"7","author":"H B","year":"1920","journal-title":"Heart"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022147"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.07.038"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.08.037"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-9473(98)00096-6"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.701243"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.06.033"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.661082"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033943"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa041"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euu086"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2012.01.014"}],"container-title":["Journal of Cardiovascular Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jce.16293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T14:58:06Z","timestamp":1720709886000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jce.16293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/jce.16293"],"URL":"https:\/\/doi.org\/10.1111\/jce.16293","archive":["Portico"],"relation":{},"ISSN":["1045-3873","1540-8167"],"issn-type":[{"value":"1045-3873","type":"print"},{"value":"1540-8167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,9]]},"assertion":[{"value":"2024-02-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}