Torsade de pointes ventricular tachyarrhythmia in the
long QT syndrome is a prime example of how molecular biology,
ion channel, and cellular and organ physiology, coupled with clinical observations, promise to be the future paradigm for advancement of medical knowledge. Both the congenital and the acquired
long QT syndrome are caused by abnormalities (intrinsic, acquired, or both) of the ionic currents underlying ventricular repolarization. In this review, the continually unraveling molecular biology of congenital
long QT syndrome is discussed. The various pharmacologic agents associated with the acquired
long QT syndrome are listed. Although it is difficult to predict which patients are at risk for
torsade de pointes, careful assessment of the risk to benefit ratio is important before prescribing drugs known to cause QT prolongation. The in vivo electrophysiologic mechanism of
torsade de pointes in the
long QT syndrome is described, using as a paradigm the
anthopleurin-A canine model, a surrogate for LQT3. The characteristic association of
torsade de pointes with T-wave alternans and short-long cardiac sequences is discussed, with emphasis on electrophysiologic mechanisms. Finally, the expanding knowledge of genetic mutations other than
long QT syndrome associated with polymorphic
ventricular tachyarrhythmia is emphasized.