Document Type
Article
Publication Date
12-26-2023
Abstract
BACKGROUND: There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF).
METHODS: The effectiveness of flecainide (1.5 µmol/L) and ibutilide (20 nmol/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary-perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 µmol/L) and ibutilide (50 nmol/L) using canine left ventricular wedge preparations.
RESULTS: Sustained AF (>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 (P<0.05 for both). Flecainide increased the effective refractory period in atria by 27% (P<0.01) but by only 2% in the ventricles. The combination of the 2 drugs lengthened the effective refractory period by 42% in atria (P<0.01) but by only 7% (P<0.05) in the ventricles. In left ventricular wedges, ibutilide prolonged QT and Tpeak-Tend intervals by 25 and 55%, respectively (P<0.05 for both; cycle length, 2000 ms). The addition of flecainide (1.5 µmol/L) partially reversed these effects (P<0.05 for both parameters versus ibutilide alone). Torsades de Pointes score was relatively high with ibutilide alone and low with the drug combination.
CONCLUSIONS: 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-mediated ventricular proarrhythmia.
Recommended Citation
Burashnikov, Alexander; Di Diego, José M.; Patocskai, Bence; Echt, Debra S.; Belardinelli, Luiz; and Antzelevitch, Charles, "Effect of Flecainide and Ibutilide Alone and in Combination to Terminate and Prevent Recurrence of Atrial Fibrillation" (2023). Division of Cardiology Faculty Papers. Paper 143.
https://jdc.jefferson.edu/cardiologyfp/143
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Language
English
PubMed ID
38146652
Comments
This article is the author's final published version in Circulation. Arrhythmia and Electrophysiology, Volume 17, Issue 1, January 2024, Article number e0124541.
The published version is available at https://doi.org/10.1161/CIRCEP.123.012454. Copyright © 2023 The Authors. Circulation: Arrhythmia and Electrophysiology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc.