The Arrhythmogenicity of Sotalol and its Role in Heart Failure: A Literature Review

Abstract

According to the American Heart Association, approximately 6 million adults have been afflicted with heart failure in the United States in 2020 and are more likely to have sudden cardiac death accounting for approximately 50% of the cause of mortality. Sotalol is a nonselective β-adrenergic receptor antagonist with class III antiarrhythmic properties that has been mostly used for atrial fibrillation treatment and suppressing recurrent ventricular tachyarrhythmias. The use of sotalol in patients with left ventricular dysfunction is not recommended by the American College of Cardiology or American Heart Association because studies are inconclusive with conflicting results regarding safety. This article aims to review the mechanism of action of sotalol, the β-blocking effects on heart failure, and provide an overview of clinical trials on sotalol use and its effects in patients with heart failure. Small- and large-scale clinical trials have been controversial and inconclusive about the use of sotalol in heart failure. Sotalol has been shown to reduce defibrillation energy requirements and reduce shocks from implantable cardioverter-defibrillators. Torsades de Pointes is the most life-threatening arrhythmia that has been documented with sotalol use and occurs more commonly in women and heart failure patients. Thus far, mortality benefits have not been demonstrated with sotalol use and larger multicenter studies are required going forward.

Application of k-Nearest Neighbors Method for Drug Concentration and Cardiotoxicity Classification Using Extracellular Field Potentials and Reconstructed Action Potentials of Cardiac Cells

“…2 shows categoriza�on of DMSO into cardiotoxicity risk groups based on normalized FPD c and STV FPDc thresholds, DMSO is widely known to be a non-toxic compound [20], but the data shows that at the highest concentra�on of 0.6%, when the FPD c and STV FPDc cross the thresholds the waveform contains FP altera�ons, which may be a marker of cardiotoxicity. On the other hand, Sotalol is a known an�arrhythmic agent [21], it is used in trea�ng certain types of cardiac arrhythmias, like atrial fibrilla�on [22] and ventricular tachycardia [23], but its capacity to prolong the QT interval at higher doses can increase the risk of a poten�ally life-threatening arrhythmia called Torsades de Pointes; addi�onally, as a beta-blocker, Sotalol can have other cardiac effects such as bradycardia. Comparison of FPDc and STV FPDc data for Sotalol shows that both FPD c and STV FPDc cross the cardiotoxicity risk threshold at the highest drug con-centra�ons of 30 and 60 nM.…”

HPLC and LC–MS/MS-Based Quantitative Characterization of Related Substances Associated with Sotalol Hydrochloride

“…First produced in 1966 [5], STHCl was listed in the UK in 1974 and provided with US Food and Drug Administration approval in 1992 [6]. It is now prescribed to treat various ventricular and supraventricular arrhythmias, offering high levels of bioavailability and a long half-life such that it is often used in clinical settings and is now available in over 40 countries worldwide [7]. The toxicological effects of drugs and associated adverse reactions are often attributable to related substances (RSs) derived from these drugs or their degradation products and there is, thus, substantial interest in the development of methods to better assess drug stability and to detect process-related or degradation-related impurities in drug preparations.…”