long qt syndrome : Pathophysiology of long qt syndrome

he QT interval represents the duration of activation and recovery of the ventricular myocardium. Prolonged recovery from electrical excitation increases the likelihood of dispersing refractoriness, when some parts of myocardium might be refractory to subsequent depolarization.

From a physiologic standpoint, dispersion occurs with repolarization between 3 layers of the heart, and the repolarization phase tends to be prolonged in the myocardium. This is why the T wave is normally wide and the interval from T_peak to T_end (T_p-e) represents the transmural dispersion of repolarization (TDR). In long QT syndrome (LQTS), TDR increases and creates a functional substrate for transmural reentry.

In LQTS, QT prolongation can lead to polymorphic ventricular tachycardia, or torsade de pointes, which itself may lead to ventricular fibrillation and sudden cardiac death. Torsade de pointes is widely thought to be triggered by reactivation of calcium channels, reactivation of a delayed sodium current, or a decreased outward potassium current that results in early afterdepolarization (EAD), in a condition with enhanced TDR usually associated with a prolonged QT interval. TDR serves as a functional reentry substrate to maintain torsade de pointes. TDR not only provides a substrate for reentry but also increases the likelihood of EAD, the triggering event for torsade de pointes, by prolonging the time window for calcium channels to remain open. Any additional condition that accelerates the reactivation of calcium channels (eg, increased sympathetic tone), increases the risk of EAD.

LQTS has been recognized as mainly Romano-Ward syndrome (ie, familial occurrence with autosomal dominant inheritance, QT prolongation, and ventricular tachyarrhythmias) or as Jervell and Lang-Nielsen (JLN) syndrome (ie, familial occurrence with autosomal recessive inheritance, congenital deafness, QT prolongation, and ventricular arrhythmias). Two other syndromes are described, namely, Andersen syndrome and Timothy syndrome, though some debate centers on whether they should be included in LQTS.