{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:22:14Z","timestamp":1776867734120,"version":"3.51.2"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Diagnosis of congenital long\u2010QT syndrome (LQTS) is complicated by phenotypic ambiguity, with a frequent normal\u2010to\u2010borderline resting QT interval. A 3\u2010step algorithm based on exercise response of the corrected QT interval (QTc) was previously developed to diagnose patients with LQTS and predict subtype. This study evaluated the 3\u2010step algorithm in a population that is more representative of the general population with LQTS with milder phenotypes and establishes sex\u2010specific cutoffs beyond the resting QTc.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We identified 208 LQTS likely pathogenic or pathogenic\n              <jats:italic>KCNQ1<\/jats:italic>\n              or\n              <jats:italic>KCNH2<\/jats:italic>\n              variant carriers in the Canadian NLQTS (National Long\u2010QT Syndrome) Registry and 215 unaffected controls from the HiRO (Hearts in Rhythm Organization) Registry. Exercise treadmill tests were analyzed across the 5 stages of the Bruce protocol. The predictive value of exercise ECG characteristics was analyzed using receiver operating characteristic curve analysis to identify optimal cutoff values. A total of 78% of male carriers and 74% of female carriers had a resting QTc value in the normal\u2010to\u2010borderline range. The 4\u2010minute recovery QTc demonstrated the best predictive value for carrier status in both sexes, with better LQTS ascertainment in female patients (area under the curve, 0.90 versus 0.82), with greater sensitivity and specificity. The optimal cutoff value for the 4\u2010minute recovery period was 440\u2009milliseconds for male patients and 450\u2009milliseconds for female patients. The 1\u2010minute recovery QTc had the best predictive value in female patients for differentiating LQTS1 versus LQTS2 (area under the curve, 0.82), and the peak exercise QTc had a marginally better predictive value in male patients for subtype with (area under the curve, 0.71). The optimal cutoff value for the 1\u2010minute recovery period was 435\u2009milliseconds for male patients and 455\u2009milliseconds for femal patients.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The 3\u2010step QT exercise algorithm is a valid tool for the diagnosis of LQTS in a general population with more frequent ambiguity in phenotype. The algorithm is a simple and reliable method for the identification and prediction of the 2 major genotypes of LQTS.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.025108","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T09:38:34Z","timestamp":1663148314000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Sex Differences and Utility of Treadmill Testing in Long\u2010QT Syndrome"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9956-3062","authenticated-orcid":false,"given":"Lauren A.","family":"Yee","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Innovation, Heart Rhythm Services, Division of Cardiology, Department of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Chen","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Innovation, Heart Rhythm Services, Division of Cardiology, Department of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-7109","authenticated-orcid":false,"given":"Brianna","family":"Davies","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Innovation, Heart Rhythm Services, Division of Cardiology, Department of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6743-9817","authenticated-orcid":false,"given":"Charles M.","family":"Pearman","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Innovation, Heart Rhythm Services, Division of Cardiology, Department of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-541X","authenticated-orcid":false,"given":"Zachary W. 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