{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:44:41Z","timestamp":1792806281241,"version":"4.5.0"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hans-and-Gertie Fischer Foundation"},{"name":"Deutsche Stiftung f\u00fcr Herzforschung","id":[{"id":"https:\/\/ror.org\/02yjb3a91","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Previous studies suggest a direct effect of sacubitril on cardiac electrophysiology and indicate potential arrhythmic interactions between sacubitril and antiarrhythmic drugs. Therefore, the aim of this study was to explore the electrophysiologic effects of combining sacubitril with the antiarrhythmic drugs d,l-sotalol and mexiletine in isolated hearts. Methods and results: A total of 25 rabbit hearts were perfused using a Langendorff setup. Following baseline data collection, hearts were treated with mexiletine (25 \u00b5M, 13 hearts) or d,l-sotalol (100 \u00b5M, 12 hearts). Monophasic action potential demonstrated an abbreviation of action potential duration (APD90) after administration of mexiletine. Spatial dispersion of repolarization remained unchanged after mexiletine treatment, whereas effective refractory periods (ERP) were significantly prolonged. D,l-sotalol prolonged cardiac repolarization and amplified spatial dispersion. Further infusion of sacubitril (5 \u00b5M) led to a significant reduction in APD90 and ERP in the mexiletine group. In the d,l-sotalol group, additional administration of sacubitril shortened cardiac repolarization duration without affecting spatial dispersion. No proarrhythmic effect was observed after mexiletine treatment as assessed by a predefined pacing protocol. Additional sacubitril treatment did not increase ventricular vulnerability. When potassium concentration was reduced, 30 episodes of torsade de pointes tachycardia occurred after d,l-sotalol treatment. Additional sacubitril treatment significantly suppressed torsade de pointes tachycardia (eight episodes) in the d,l-sotalol-group. Conclusions: In class IB- and class III-pretreated hearts, sacubitril shortened refractory periods and cardiac repolarization duration. The combination of sacubitril with the antiarrhythmic drugs d,l-sotalol and mexiletine demonstrates a safe electrophysiologic profile and sacubitril reduces the occurrence of class III-related proarrhythmia, i.e., torsade de pointes tachycardia.<\/jats:p>","DOI":"10.3390\/ph18020230","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T05:53:22Z","timestamp":1739166802000},"page":"230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sacubitril Does Not Exert Proarrhythmic Effects in Combination with Different Antiarrhythmic Drugs"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9172-296X","authenticated-orcid":false,"given":"Christian","family":"Ellermann","sequence":"first","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Mengel","sequence":"additional","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Wolfes","sequence":"additional","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-645X","authenticated-orcid":false,"given":"Felix K.","family":"Wegner","sequence":"additional","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-352X","authenticated-orcid":false,"given":"Julia","family":"K\u00f6be","sequence":"additional","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3735-8503","authenticated-orcid":false,"given":"Lars","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1431-9886","authenticated-orcid":false,"given":"Gerrit","family":"Frommeyer","sequence":"additional","affiliation":[{"name":"Department of Cardiology II (Electrophysiology), University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. 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