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

Purpose: To review the current understanding of the mechanisms and tre atment 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 clinica l studies and topical reviews on the electrophysiologic mechanisms and treatment of torsade de pointes were analyzed. Results: The long QT i nterval syndromes have been classified into acquired and hereditary fo rms, both of which are associated with a characteristic type of life-t hreatening polymorphic ventricular tachycardia called torsade de point es. The acquired form is caused by various agents and conditions that reduce the magnitude of outward repolarizing K+ currents, enhance inwa rd depolarizing Na+ or Ca2+ currents, or both, thereby triggering the development of early afterdepolarizations that initiate the tachyarrhy thmia. The hereditary form appears to result from an abnormal response to adrenergic or sympathetic nervous system stimulation. At least som e 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 th e acquired form is primarily directed at identifying and withdrawing t he offending agent, although emergent therapy using maneuvers and agen ts that favorably modulate transmembrane ion currents can be lifesavin g. In torsade de pointes associated with the hereditary long QT interv al syndromes, early diagnosis leading to treatments designed to both s horten the QT interval and block the beta-adrenergic-induced instabili ty of the QT interval is essential. Conclusions: The long QT interval syndromes and torsade de pointes are potentially life-threatening cond itions caused by various agents, conditions, and genetic defects. The mechanisms responsible for these conditions and available treatment op tions for them are reviewed.