Understanding of arrhythmogenesis associated with abnormal ventricular repolarization has increased in recent years, but the challenge to establish predictable arrhythmogenic markers remains.
Ventricular repolarization is dependent on the fine balance between depolarizing and repolarizing currents during the action potential (AP) plateau, as reviewed by Dr. Varró (Szeged, Hungary). Reduction of the net repolarizing current or repolarization reserve leads to increased variability of repolarization. Dr. Zaza (Milano, Italy) emphasized that repolarization reserve during ß-adrenergic activation is strongly rate-dependent.
In the absence of heart-rate acceleration, ß-adrenergic activation leads to a mismatch wherein inward exceeds outward current, thus reducing repolarization reserve and promoting variability of AP duration and arrhythmogenesis. These mechanisms may underlie TdP in patients with long-QT (LQT) syndrome and concomitant AV block. Dr. Richard (Montpellier, France) discussed the role of intracellular calcium fluctuations as a cause of repolarization lability in the failing heart after myocardial infarction. Dysregulation of calcium-handling proteins leads to spontaneous release of calcium from the sarcoplasmic reticulum, favoring the development of afterdepolarizations and arrhythmias.
Dr. Rosenbaum (Cleveland, USA), who developed T-wave alternans as a major predictor of sudden arrhythmic death in selected patient groups, reviewed the cellular mechanisms underlying this type of alternans and emphasized the role for altered kinetics of calcium cycling. Dr. Vos (Utrecht, The Netherlands) demonstrated the usefulness of short-term variability of monophasic AP duration and QT interval to predict torsades de pointes in a dog model, and (in collaboration with Dr. Kääb, Munich, Germany) in congenital and drug-induced LQT patients. |