Torsades de pointes (TdP) is a malignant polymorphic ventricular tachyarrhythmia that can be caused by drugs that induce electrophysiological changes. Although the number of drugs known to cause TdP has increased in recent years, there is no cell-based assay, in vitro heart preparation or animal model that predicts the potential of a drug to induce TdP in humans. Nevertheless, certain electrophysiological events are known to be associated with the development of TdP. For example, a drug that prolongs action potential duration, induces early afterdepolarizations and ectopic beats, and increases dispersion of ventricular repolarization is likely to cause TdP. By contrast, a drug that does not induce these changes is unlikely to cause TdP. The exact relationship between these electrophysiological events and the development of TdP has not been defined, but the potential of a drug to elicit these events might predict its pro-arrhythmic risk.
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone
A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents
Electrophysiologic substrate of torsade de pointes: dispersion of repolarization or early afterdepolarizations?
A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes
A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation
Amiodarone-associated proarrhythmic effects. A review with special reference to torsade de pointes tachycardia
Drug-induced afterdepolarizations and triggered activity occur in a discrete subpopulation of ventricular muscle cells (M cells) in the canine heart: quinidine and digitalis
Proarrhythmic effects of the class III agent almokalant: importance of infusion rate, QT dispersion, and early afterdepolarisations
The electrophysiological mechanism of ventricular arrhythmias in the long QT syndrome. Tridimensional mapping of activation and recovery patterns
Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart
Role of interventricular dispersion of repolarization in acquired torsade-de-pointes arrhythmias: reversal by magnesium
Further observations to elucidate the role of interventricular dispersion of repolarization and early afterdepolarizations in the genesis of acquired torsade de pointes arrhythmias: a comparison between almokalant and d-sotalol using the dog as its own control
New insight into repolarization abnormalities in patients with congenital long QT syndrome: the increased transmural dispersion of repolarization
Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study
Enhanced susceptibility for acquired torsade de pointes arrhythmias in the dog with chronic, complete AV block is related to cardiac hypertrophy and electrical remodeling
Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome
Sodium pentobarbital reduces transmural dispersion of repolarization and prevents torsades de Pointes in models of acquired and congenital long QT syndrome
Risk of torsades de pointes with non-cardiac drugs. Doctors need to be aware that many drugs can cause qt prolongation
Cesium chloride induced ventricular arrhythmias in dogs: three-dimensional activation patterns and their relation to the cesium dose applied
Progress in the understanding of cardiac early afterdepolarizations and torsades de pointes: time to revise current concepts
The potential for QT prolongation and pro-arrhythmia by non-anti-arrhythmic drugs: clinical and regulatory implications. Report on a Policy Conference of the European Society of Cardiology
Azimilide and dofetilide produce similar electrophysiological and proarrhythmic effects in a canine model of Torsade de Pointes arrhythmias
Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic
Chromanol 293B inhibits slowly activating delayed rectifier and transient outward currents in canine left ventricular myocytes
Phase 2 prolongation, in the absence of instability and triangulation, antagonizes class III proarrhythmia
Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome : direct evidence from intracellular recordings in the intact left ventricular wall
Chronic amiodarone evokes no torsade de pointes arrhythmias despite QT lengthening in an animal model of acquired long-QT syndrome
Electrophysiologic characterization of the antipsychotic drug sertindole in a rabbit heart model of torsade de pointes: low torsadogenic potential despite QT prolongation
Electrophysiologic parameters and predisposing factors in the generation of drug-induced Torsade de Pointes arrhythmias
Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes
Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties
Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine
Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes
Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges
Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation
High-precision recording of the action potential in isolated cardiomyocytes using the near-infrared fluorescent dye di-4-ANBDQBS
Recent advances in the management of chronic stable angina II. Anti-ischemic therapy, options for refractory angina, risk factor reduction, and revascularization
Low serum magnesium concentrations are associated with a high prevalence of premature ventricular complexes in obese adults with type 2 diabetes
Preclinical cardio-safety assessment of torsadogenic risk and alternative methods to animal experimentation: the inseparable twins
Electrophysiological and proarrhythmic parameters in transmural canine left-ventricular needle biopsies
A new method to calculate the beat-to-beat instability of QT duration in drug-induced long QT in anesthetized dogs
Effects of sarcolemmal Ca(2+) entry, ryanodine function, and kinase inhibitors on a rabbit model of heart failure
Electrocardiograms (ECGs) in phase I anticancer drug development: the MD Anderson Cancer Center experience with 8518 ECGs
Transmural dispersion of repolarization determines scroll wave behavior during ventricular tachyarrhythmias
The use of electrocardiograms in clinical trials: a public discussion of the proposed ICH E14 regulatory guidance. April 11-12, 2005, Bethesda, MD, USA
Effects of K201 on repolarization and arrhythmogenesis in anesthetized chronic atrioventricular block dogs susceptible to dofetilide-induced torsade de pointes
The continuing evolution of torsades de pointes liability testing methods: is there an end in sight?
Effects of epinephrine over P wave duration and ventricular repolarization in subjects without structural heart disease
Identify drug-induced T wave morphology changes by a cell-to-electrocardiogram model and validation with clinical trial data
Age-related differences of QT interval and autonomic nervous system activity in female cynomolgus monkeys
Evaluation of drug-induced QT prolongation in a halothane-anesthetized monkey model: effects of sotalol
Preclinical Torsades-de-Pointes screens: advantages and limitations of surrogate and direct approaches in evaluating proarrhythmic risk
Temporal variability of QT interval and changes in T wave morphology in dogs as markers of the clinical risk of drug-induced proarrhythmia
Preclinical assessment of drug-induced proarrhythmias: role of the arterially perfused rabbit left ventricular wedge preparation
Action potential experiments complete hERG assay and QT-interval measurements in cardiac preclinical studies
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