Related Experiment Videos
Electrophysiologic mechanisms for ventricular arrhythmias in left ventricular dysfunction: electrolytes,
1Division of Investigative Medicine, Mt. Sinai Medical Center, Cleveland, OH 44106.
Insights
Calcium plays a role in cardiac arrhythmias, influencing automaticity and conduction. Understanding afterdepolarizations, like early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), is crucial for managing arrhythmias such as torsade de pointes.
Area of Science:
- Cardiology
- Electrophysiology
- Pharmacology
Background:
- Cardiac arrhythmias stem from disruptions in automaticity or impulse conduction.
- Calcium ions are implicated in arrhythmogenesis, though calcium antagonists have limited efficacy in ventricular arrhythmias.
- Partially depolarized myocardial cells can generate ectopic beats, contributing to arrhythmias.
Purpose of the Study:
- To explore the role of calcium in cardiac arrhythmias.
- To differentiate mechanisms of early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs).
- To review therapeutic strategies for specific arrhythmias like torsade de pointes and ventricular tachycardia.
Main Methods:
- Review of existing literature on cardiac electrophysiology and antiarrhythmic mechanisms.
- Analysis of the role of calcium, afterdepolarizations, and ion channel function in arrhythmia generation.
- Examination of clinical and animal model data regarding torsade de pointes and ventricular tachycardia.
Main Results:
- EADs, induced by partial depolarization, can initiate torsade de pointes, particularly with QT prolongation.
- DADs are linked to calcium overload.
- Treatments like magnesium, isoproterenol, and pacing can suppress EADs and torsade de pointes.
- Ventricular tachycardia arises from re-entry and can be worsened by certain antiarrhythmics (e.g., Class 1c).
- Proarrhythmia prediction in individual patients is challenging.
Conclusions:
- Calcium dysregulation contributes significantly to cardiac arrhythmias.
- EADs and DADs represent distinct electrophysiological events with different triggers and clinical implications.
- Therapeutic interventions targeting EADs show promise for specific arrhythmias.
- Risk stratification for proarrhythmia is essential, especially in patients with left ventricular dysfunction or prior sustained ventricular tachycardia.
Abstract:
Cardiac arrhythmias are generated as the result of disorders of automaticity or of impulse conduction. Regardless of the mechanism, calcium is likely to be involved, although calcium antagonists are rarely useful antiarrhythmics in ventricular arrhythmias. Myocardial cells that do not ordinarily initiate action potentials may do so when they are partially depolarized, giving rise to an ectopic focus. Early afterdepolarizations (EADs) are also induced in cardiac cells by partial depolarization, whereas delayed afterdepolarizations (DADs) are induced by Ca++ overloading. EADs may be the initiating mechanism of torsade de pointes, a complication of QT prolongation associated with quinidine therapy. Both in the animal model and in humans, treatment with magnesium, isoproterenol, or pacing, all of which suppress EADs, will also suppress torsade de pointes. Ventricular tachycardia is a manifestation of ordered re-entry, and may be exacerbated by antiarrhythmics, especially class 1c drugs. In the individual patient, prediction of proarrhythmia is not possible. The risk of proarrhythmia is increased in patients with episodes of sustained ventricular tachycardia or with significant left ventricular dysfunction.