{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:08:01Z","timestamp":1789553281588,"version":"build-2803163510"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,6,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Bepridil is an antiarrhythmic drug used to treat paroxysmal atrial fibrillation; however, its use is limited by corrected QT interval (QTc) prolongation and the risk of ventricular arrhythmias. This study aimed to identify genetic variants associated with bepridil\u2010associated QTc prolongation after catheter ablation for paroxysmal atrial fibrillation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A total of 523 patients who initiated bepridil therapy after catheter ablation at Hiroshima University between November 2013 and March 2023 were enrolled. Of these, 445 patients were included in a genome\u2010wide association study, and 78 were used as an independent replication cohort. QTc was measured 1 month after treatment initiation, with QTc prolongation defined as \u2265450\u2009ms in men and \u2265460\u2009ms in women. Logistic regression analyses were conducted using additive, dominant, and recessive genetic models. Variants showing suggestive associations in the genome\u2010wide association study (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;1.00\u00d710\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) were evaluated in the replication cohort, followed by random\u2010effects meta\u2010analyses, with genome\u2010wide significance defined as\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;5.00\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      . Linear regression analyses were conducted for QTc prolongation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      After quality control, 443 patients were analyzed in the genome\u2010wide association study. Of these, 122 (28%) exhibited QTc prolongation. Under the recessive model, rs12622919, an intronic variant in the\n                      <jats:italic toggle=\"no\">FSHR<\/jats:italic>\n                      (follicle\u2010stimulating hormone receptor) gene, showed a suggestive association. In the random\u2010effects meta\u2010analysis combining the discovery and replication cohorts, rs12622919 reached genome\u2010wide significance. Exploratory sex\u2010stratified analyses suggested a potential association in women (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.026), although no statistically significant genotype\u2010by\u2010sex interaction was observed. Inclusion of rs12622919 improved discrimination for QTc prolongation (area under the curve, 0.77 [95% CI, 0.70\u20130.84]; Welch's\n                      <jats:italic toggle=\"no\">t<\/jats:italic>\n                      test,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001), with the improvement remaining significant by DeLong's test (area under the curve, 0.78 [95% CI, 0.74\u20130.84];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.0078).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The\n                      <jats:italic toggle=\"no\">FSHR<\/jats:italic>\n                      variant rs12622919 is associated with bepridil\u2010associated QTc prolongation and may serve as a genetic biomarker for individual risk assessment. Because the findings are based on meta\u2010analysis, independent validation is required.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047046","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T11:52:03Z","timestamp":1781005923000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Investigation of Corrected QT Interval Sensitivity to Oral Bepridil Hydrochloride Hydrate in Patients With Atrial Fibrillation"],"prefix":"10.1161","volume":"15","author":[{"given":"Naoki","family":"Ishibashi","sequence":"first","affiliation":[{"name":"Hiroshima University Graduate School of Biomedical and Health Sciences","place":["Hiroshima, 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