DOI: 10.1152/ajpheart.00227.2023 ISSN:

Amiodarone Prevents Wave Front-Tail Interactions in Heart Failure Patients: An In-silico Study

Richard A. Gray, Michael R. Franz
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine
  • Physiology

Background: Amiodarone (AM) is an anti-arrhythmic drug whose chronic use has proved effective in preventing ventricular arrhythmias in a variety of patient populations, including those with heart failure. AM has both Class III (i.e., it prolongs the action potential duration, APD, via blocking potassium channels) and Class I (i.e., it affects the rapid sodium channel) properties; however, the specific mechanism(s) by which it prevents reentry formation in HF patients remain unknown. Objective: To test the hypothesis that AM prevents reentry induction in HF during programmed electrical stimulation (PES) via its ability to induce post-repolarization refractoriness (PRR) via its Class I effects on sodium channels. Results: Here we extend our previous human action potential model to represent the effects of both HF and AM separately by calibrating to human tissue and clinical PES data respectively. We then combine these models (HF+AM) to test our hypothesis. Results from simulations in cells and cables suggest that AM acts to increase PRR and decrease the elevation of take-off potential. The ability of AM to prevent reentry was studied in-silico in two-dimensional sheets in which a variety of APD gradients (ΔAPD) were imposed. Reentrant activity was induced in all HF simulations but was prevented in 23 of 24 HF+AM models. Eliminating the AM-induced slowing of the recovery of inactivation of the sodium channel restored the ability to induce reentry. Conclusions: In-silico testing suggests that chronic AM treatment prevents reentry induction in HF patients during PES via its Class I effect to induce PRR.

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