Safe electrophysiologic profile of the neprilysin-inhibitor sacubitril in combination with different antiarrhythmic drugs

Autor: G Frommeyer, C Mengel, J Wolfes, L Eckardt, C Ellermann
Rok vydání: 2022
Předmět:
Zdroj: European Heart Journal. 43
ISSN: 1522-9645
0195-668X
Popis: Background Observational clinical data suggest a direct effect of sacubitril on cardiac electrophysiology. However, data concerning the impact of combination of sacubitril with antiarrhythmic drug therapy is sparse. Purpose We aimed at characterizing the electrophysiologic effects of a combination therapy of sacubitril with the class III-drug sotalol and the class IB-agent mexiletine in a sensitive, experimental whole-heart model. Methods and results 25 isolated rabbit hearts were retrogradely perfused. Hearts were treated with mexiletine (25 μM, 13 hearts) or sotalol (100 μM, 12 hearts) after generating baseline data. Eight endo- and epicardial monophasic action potentials and ECG recordings demonstrated an abbreviation of action potential duration (APD90, −21 ms, p Conclusion Sacubitril in combination with antiarrhythmic drugs demonstrates a safe electrophysiologic profile. In class IB- and class III-pretreated hearts, sacubitril abbreviates cardiac repolarization duration and effective refractory periods without changing spatial dispersion of repolarization. Thereby, sacubitril reduces the occurrence of torsade de pointes-tachycardia in antiarrhythmic pretreated hearts. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Deutsche Stiftung für Herzforschung (to G.F.)
Databáze: OpenAIRE