Key result
Amiodarone exerts its physiologic effects mainly through IKr blockade but displays less risk of inducing long QT syndrome and torsade de pointes compared to other class III antiarrhythmics.
Why the study?
Unlike other class III antiarrhythmics that cause long QT syndrome progressing to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia.
This review highlights the electropharmacological effects of amiodarone on the myocardium, explaining its lower risk of inducing torsade de pointes despite being a class III antiarrhythmic.
Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (IKr). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through IKr blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca2+ current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium.
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Gelman et al. (2024) conducted a review in Atrial and ventricular arrhythmias. Amiodarone vs. Other class III antiarrhythmics (e.g., sotalol, dofetilide) was evaluated. Amiodarone exerts its physiologic effects mainly through IKr blockade but displays less risk of inducing long QT syndrome and torsade de pointes compared to other class III antiarrhythmics.
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