Why the study?
Amiodarone is frequently used to maintain sinus rhythm in AF but impairs SAN function in one-third of patients, prompting a need for mechanistic insights into antiarrhythmic drug effects in AF-induced SND.
Do antiarrhythmic agents like amiodarone and disopyramide alter heart rate in a computational model of AF-induced sinus node dysfunction?
Do antiarrhythmic agents like amiodarone and disopyramide alter heart rate in a computational model of AF-induced sinus node dysfunction?
Computational modeling suggests that disopyramide, unlike amiodarone, may increase heart rate in AF-induced sinus node dysfunction, potentially reversing the SND phenotype.
Model-based insights into amiodarone effects on AF-induced SND are hypothesis-generating; prospective validation required before practice change.
Sinus node dysfunction (SND) is often associated with atrial fibrillation (AF). Amiodarone is the most frequently used agent for maintaining sinus rhythm in patients with AF, but it impairs the sinoatrial node (SAN) function in one-third of AF patients. This study aims to gain mechanistic insights into the effects of the antiarrhythmic agents in the setting of AF-induced SND. We have adapted a human SAN model to characterize the SND conditions by incorporating experimental data on AF-induced electrical remodelling, and then integrated actions of drugs into the modified model to assess their efficacy. Reductions in pacing rate upon the implementation of AF-induced electrical remodelling associated with SND agreed with the clinical observations. And the simulated results showed the reduced funny current ( I f ) in these remodelled targets mainly contributed to the heart rate reduction. Computational drug treatment simulations predicted a further reduction in heart rate during amiodarone administration, indicating that the reduction was the result of actions of amiodarone on I Na , I Kur , I CaL , I CaT , I f and beta-adrenergic receptors. However, the heart rate was increased in the presence of disopyramide. We concluded that disopyramide may be a desirable choice in reversing the AF-induced SND phenotype.
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Bai et al. (2020) studied this question.
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