Antiarrhythmic drugs and torsade de pointes
1University of Oklahoma Health Sciences Center, Oklahoma City.
European Heart Journal
|November 1, 1993
Summary
Drug-induced long QT syndromes and torsade de pointes (TdP) are linked by electrophysiological mechanisms. Understanding TdP proarrhythmia helps differentiate antiarrhythmic drug effects from adverse events.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Significant advancements in understanding drug-induced long QT syndromes (LQTS) and their relationship with other LQTS types.
- Focus on electrophysiological mechanisms underlying torsade de pointes (TdP), a critical proarrhythmic event associated with prolonged repolarization.
Purpose of the Study:
- To elucidate the electrophysiological basis of TdP, particularly the role of after-depolarizations.
- To analyze the concordance and discordance of various antiarrhythmic agents in inducing TdP.
- To explore how QT interval prolongation relates to TdP risk and therapeutic effects of Class III agents.
Main Methods:
- Review of clinical features and associations of drug-induced LQTS.
- Analysis of electrophysiological mechanisms, including after-depolarizations, hypokalemia, and bradycardia.
- Comparison of TdP incidence with QT prolongation for different antiarrhythmic agents.
Main Results:
- Torsade de pointes is primarily caused by after-depolarizations, exacerbated by hypokalemia, bradycardia, and prolonged QT intervals.
- Certain antiarrhythmic drugs (quinidine, disopyramide, procainamide) show strong concordance in TdP production, suggesting individual predisposition.
- Amiodarone appears discordant, while sotalol's concordance is less certain, highlighting variability in TdP risk among repolarization-prolonging agents.
Conclusions:
- Individual predisposition plays a role in susceptibility to drug-induced early after-depolarizations (EADs).
- Discordance between QT prolongation and TdP risk is key to distinguishing therapeutic from proarrhythmic effects of Class III agents.
- New agents prolonging repolarization offer potential for anti-reentrant and antitachyarrhythmic actions.
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