ELECTROPHYSIOLOGIC MECHANISMS OF THE LONG QT INTERVAL SYNDROMES AND TORSADE-DE-POINTES

Purpose: To review the current understanding of the mechanisms and treatment of the long QT interval syndromes and torsade de pointes. Data Sources: Personal databases of the authors and a search of the MEDLINE database from 1966 to 1994. Study Selection: Experimental and clinical studies and topical reviews on the electrophysiologic mechanisms and treatment of torsade de pointes were analyzed. Results: The long QT interval syndromes have been classified into acquired and hereditary forms, both of which are associated with a characteristic type of life-threatening polymorphic ventricular tachycardia called torsade de pointes. The acquired form is caused by various agents and conditions that reduce the magnitude of outward repolarizing K+ currents, enhance inward depolarizing Na+ or Ca2+ currents, or both, thereby triggering the development of early afterdepolarizations that initiate the tachyarrhythmia. The hereditary form appears to result from an abnormal response to adrenergic or sympathetic nervous system stimulation. At least some cases of the hereditary long QT interval syndromes may result from a single gene defect that alters the intracellular regulatory proteins responsible for the modulation of K+ channel function. Treatment of the acquired form is primarily directed at identifying and withdrawing the offending agent, although emergent therapy using maneuvers and agents that favorably modulate transmembrane ion currents can be lifesaving. In torsade de pointes associated with the hereditary long QT interval syndromes, early diagnosis leading to treatments designed to both shorten the QT interval and block the beta-adrenergic-induced instability of the QT interval is essential. Conclusions: The long QT interval syndromes and torsade de pointes are potentially life-threatening conditions caused by various agents, conditions, and genetic defects. The mechanisms responsible for these conditions and available treatment options for them are reviewed.