{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:15:34Z","timestamp":1793452534297,"version":"4.5.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Long QT syndrome is a potentially lethal yet highly treatable cardiac channelopathy. Although \u03b2-blocker therapy is standard for most patients, concomitant therapy with sodium channel blockers, like mexiletine, is often utilized for patients with sodium channel\u2013mediated type 3 long QT syndrome (LQT3). The potential role of sodium channel blockers in patients with potassium channel\u2013mediated long QT syndrome (ie, LQT1 and LQT2) has not been investigated in detail.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We performed a retrospective chart review on 12 patients (5 females; median age at diagnosis 14.1 years (interquartile range [IQR], 7.7\u201323; range, 0\u201359, median heart rate\u2013corrected QT interval [QTc] at diagnosis 557 ms (IQR, 529\u2013605) with genetically established LQT2 (10) or a combination of LQT1\/LQT2 (1) or LQT2\/LQT3 (1), who received mexiletine. Data were collected on symptomatic status, treatments, and breakthrough cardiac events after diagnosis and initiation of treatment. Additionally, 12-lead ECGs were collected at diagnosis, before initiation of mexiletine and following mexiletine to evaluate the drug\u2019s effect on QTc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Before diagnosis, 6 patients were symptomatic and, before initiation of mexiletine, 4 patients experienced \u22651 breakthrough cardiac event on \u03b2-blocker. Median age at first mexiletine dose was 24.3 years (IQR, 14\u201332.4). After mexiletine, the median QTc decreased by 65\u00b145 ms from 547 ms (IQR, 488\u2013558) premexiletine to 470 ms (IQR, 409\u2013529) postmexiletine (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0005) for all patients. In 8 patients (67%), the QTc decreased by \u2265 40 ms with a mean decrease in QTc of 91 ms (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.008). For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Although commonly prescribed in patients with LQT3, mexiletine also shortens the QTc significantly in two-thirds of a small subset of patients with potassium channel\u2013mediated LQT2. In patients with LQT2, pharmacological targeting of the physiological late sodium current may provide added therapeutic efficacy to \u03b2-blocker therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circep.118.007280","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T05:00:25Z","timestamp":1555909225000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":115,"title":["Mexiletine Shortens the QT Interval in Patients With Potassium Channel\u2013Mediated Type 2 Long QT Syndrome"],"prefix":"10.1161","volume":"12","author":[{"given":"J. Martijn","family":"Bos","sequence":"first","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (J.M.B., R.K.R., M.J.A.), Mayo Clinic, Rochester, MN."},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory) (J.M.B., M.J.A.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Crotti","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Center for Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy (L.C., S.C., F.D., P.J.S.)."},{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, Italy (L.C.)."},{"name":"Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy (L.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram K.","family":"Rohatgi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (J.M.B., R.K.R., M.J.A.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Castelletti","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Center for Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy (L.C., S.C., F.D., P.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Dagradi","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Center for Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy (L.C., S.C., F.D., P.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Center for Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy (L.C., S.C., F.D., P.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (J.M.B., R.K.R., M.J.A.), Mayo Clinic, Rochester, MN."},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory) (J.M.B., M.J.A.), Mayo Clinic, Rochester, MN."},{"name":"Division of Heart Rhythm Services, Department of Cardiovascular Medicine (M.J.A.), Mayo Clinic, Rochester, 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patient response to the antiarrhythmic mexiletine based on genetic variation: personalized medicine for long QT syndrome.","volume":"24","author":"Zhu W","year":"2019","unstructured":"Zhu, W, Mazzanti, A, Voelker, T, Hou, P, Moreno, JD, Angsutararux, P, Naegle, KM, Priori, SG, Silva, JR. 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