{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:48:47Z","timestamp":1788544127024,"version":"build-2803163510"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Pathogenic variation in the\n              <jats:italic>ATP1A3<\/jats:italic>\n              \u2010encoded sodium\u2010potassium ATPase, ATP1A3, is responsible for alternating hemiplegia of childhood (AHC). Although these patients experience a high rate of sudden unexpected death in epilepsy, the pathophysiologic basis for this risk remains unknown. The objective was to determine the role of\n              <jats:italic>ATP1A3<\/jats:italic>\n              genetic variants on cardiac outcomes as determined by QT and corrected QT (QTc) measurements.\n            <\/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 analyzed 12\u2010lead ECG recordings from 62 patients (male subjects=31, female subjects=31) referred for AHC evaluation. Patients were grouped according to AHC presentation (typical versus atypical),\n              <jats:italic>ATP1A3<\/jats:italic>\n              variant status (positive versus negative), and\n              <jats:italic>ATP1A3<\/jats:italic>\n              variant (D801N versus other variants). Manual remeasurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. QTc measurements were significantly shorter in patients with positive\n              <jats:italic>ATP1A3<\/jats:italic>\n              variant status (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) than in patients with genotype\u2010negative status, and significantly shorter in patients with the ATP1A3\u2010D801N variant than patients with other variants (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). The mean QTc for ATP1A3\u2010D801N was 344.9\u00a0milliseconds, which varied little with age, and remained &lt;370\u00a0milliseconds throughout adulthood.\n              <jats:italic>ATP1A3<\/jats:italic>\n              genotype status was significantly associated with shortened QTc by multivariant regression analysis. Two patients with the ATP1A3\u2010D801N variant experienced ventricular fibrillation, resulting in death in 1 patient. Rare variants in\n              <jats:italic>ATP1A3<\/jats:italic>\n              were identified in a large cohort of genotype\u2010negative patients referred for arrhythmia and sudden unexplained death.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Patients with AHC who carry the ATP1A3\u2010D801N variant have significantly shorter QTc intervals and an increased likelihood of experiencing bradycardia associated with life\u2010threatening arrhythmias.\n              <jats:italic>ATP1A3<\/jats:italic>\n              variants may represent an independent cause of sudden unexplained death. Patients with AHC should be evaluated to identify risk of sudden death.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.019887","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T09:07:32Z","timestamp":1630141652000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["<i>ATP1A3<\/i>\n            \u2010Encoded Sodium\u2010Potassium ATPase Subunit Alpha 3 D801N Variant Is Associated With Shortened QT Interval and Predisposition to Ventricular Fibrillation Preceded by Bradycardia"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-6750","authenticated-orcid":false,"given":"Mary E.","family":"Moya\u2010Mendez","sequence":"first","affiliation":[{"name":"Department of Pediatrics Division of Pediatric Cardiology Duke University School of Medicine Durham 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