Early Afterdepolarizations, U Waves, and Torsades de Pointes

Abstract

Torsades de pointes (TdP) is defined as a polymorphic ventricular tachycardia (VT) with a twisting QRS morphology associated with a prolonged QT interval and/or increased U wave amplitude in the ECG.1,2⇓ Patients with acquired or congenital long-QT syndrome (LQTS) can develop TdP that results in sudden cardiac death. Fifty or more drugs, both typical antiarrhythmic agents such as quinidine as well as other classes of drugs such as some antibiotics, affect membrane ionic currents, prolong the duration of the QT interval in the ECG, and have been associated with the acquired LQTS.3 Similarly, inherited genetic defects in the cardiac membrane ion channels can cause congenital LQTS. Some patients with apparent acquired LQTS may actually have mild congenital forms and remain asymptomatic until exposed to one of the drugs noted above.4 Congenital LQTS can be divided into multiple subtypes depending on the affected membrane ionic currents (eg, LQT1, LQT2, and LQT3 for alterations in I Ks, I Kr, and the inactivation process of I Na+). Due to the possible fatal outcome and involvement of many drugs, it is important to understand the mechanism of TdP, predict its occurrence, and manage it clinically. See p 770 It has been suggested that an early afterdepolarization (EAD) exceeding the activation threshold, arising from the endocardium (including the Purkinje network)5 or from the mid-myocardial region,6 could initiate TdP.2,7⇓ EADs have been observed experimentally in monophasic action potential recordings at multiple epicardial and endocardial sites.8 Increased dispersion of repolarization preceding the TdP induction has been noted in an isolated rabbit heart model of LQT2.9 Long intervals between activations, ie, slow rates, prolong the duration of the action potential and increase the transmural dispersion of …