{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:15:42Z","timestamp":1793502942565,"version":"4.5.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>The effectiveness of flecainide (1.5 \u00b5mol\/L) and ibutilide (20 nmol\/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary\u2013perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 \u00b5mol\/L) and ibutilide (50 nmol\/L) using canine left ventricular wedge preparations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Sustained AF (&gt;1 hour) was inducible in 100%, 60%, 20%, and 0% of atria in the presence of acetylcholine alone, acetylcholine+ibutilide, acetylcholine+flecainide, and acetylcholine+ibutilide+flecainide, respectively. When used alone, flecainide and ibutilide cardioverted sustained AF in 40% and 20% of atria, respectively, but in 100% of atria when used in combination. Ibutilide prolonged atrial and ventricular effective refractory period by 15% and 8%, respectively, at a cycle length of 500 ms (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.05 for both). Flecainide increased the effective refractory period in atria by 27% (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.01) but by only 2% in the ventricles. The combination of the 2 drugs lengthened the effective refractory period by 42% in atria (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.01) but by only 7% (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.05) in the ventricles. In left ventricular wedges, ibutilide prolonged QT and T\n              <jats:sub>peak<\/jats:sub>\n              -T\n              <jats:sub>end<\/jats:sub>\n              intervals by 25 and 55%, respectively (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.05 for both; cycle length, 2000 ms). The addition of flecainide (1.5 \u00b5mol\/L) partially reversed these effects (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.05 for both parameters versus ibutilide alone). Torsades de Pointes score was relatively high with ibutilide alone and low with the drug combination.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>In our experimental model, a combination of flecainide and ibutilide significantly improves cardioversion and prevents the recurrence of AF compared with monotherapies with little to no risk for the development of long-QT\u2013mediated ventricular proarrhythmia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.123.012454","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T10:00:10Z","timestamp":1703584810000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of Flecainide and Ibutilide Alone and in Combination to Terminate and Prevent Recurrence of Atrial Fibrillation"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7198-0363","authenticated-orcid":true,"given":"Alexander","family":"Burashnikov","sequence":"first","affiliation":[{"name":"Lankenau Institute for Medical Research, Wynnewood, PA (A.B., J.M.D.D., B.P., C.A.)."},{"name":"Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA (A.B., C.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-6659","authenticated-orcid":true,"given":"Jos\u00e9 M.","family":"Di Diego","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research, Wynnewood, PA (A.B., J.M.D.D., B.P., C.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Patocskai","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research, Wynnewood, PA (A.B., J.M.D.D., B.P., C.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2991-8124","authenticated-orcid":true,"given":"Debra S.","family":"Echt","sequence":"additional","affiliation":[{"name":"InCarda Therapeutics, Inc, Newark, CA (D.S.E., L.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz","family":"Belardinelli","sequence":"additional","affiliation":[{"name":"InCarda Therapeutics, Inc, Newark, CA (D.S.E., L.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7349-1582","authenticated-orcid":true,"given":"Charles","family":"Antzelevitch","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research, Wynnewood, PA (A.B., J.M.D.D., B.P., C.A.)."},{"name":"Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA (A.B., C.A.)."},{"name":"Lankenau Heart Institute, Main Line Health System, Wynnewood, PA (C.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2019.12.041"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9149(96)00566-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa612"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(96)00121-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2006.00388.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000510"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.198887"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.704890"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.08.600"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2006.04.021"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.94.7.1613"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2112"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2011.03.045"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000892"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198500294-00014"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.115.002856"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2023.01.035"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.66.3.789"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.82.1.289"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.10.005"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.91.6.1799"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0022-3565(24)37551-2","article-title":"Ionic mechanism of ibutilide in human atrium: evidence for a drug-induced Na+ current through a nifedipine inhibited inward channel.","volume":"286","author":"Lee KS","year":"1998","unstructured":"Lee, KS, Lee, EW. Ionic mechanism of ibutilide in human atrium: evidence for a drug-induced Na+ current through a nifedipine inhibited inward channel. J Pharmacol Exp Ther. 1998;286:9\u201322.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2014.12.033"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartjsupp\/suac073"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2022.12.021"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2022.01.001"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.05.051"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.96.12.4298"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9149(97)00395-0"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.04.056"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1054\/JCPT.2000.8690"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2023.05.005"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31824e1b93"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2008.09.015"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001129"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.186395"}],"container-title":["Circulation: Arrhythmia and Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCEP.123.012454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T21:07:46Z","timestamp":1748552866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCEP.123.012454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1161\/CIRCEP.123.012454"],"URL":"https:\/\/doi.org\/10.1161\/circep.123.012454","relation":{},"ISSN":["1941-3149","1941-3084"],"issn-type":[{"value":"1941-3149","type":"print"},{"value":"1941-3084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2023-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}