Early afterdepolarizations and cardiac arrhythmias

Early afterdepolarizations (EADs) are an important cause of lethal ventricular arrhythmias in long QT syndromes and heart failure, but the mechanisms by which EADs at the cellular scale cause arrhythmias such as polymorphic ventricular tachycardia (PVT) and torsades de pointes (TdP) at the tissue scale are not well understood. Here we summarize recent progress in this area, discussing (1) the ionic basis of EADs, (2) evidence that deterministic chaos underlies the irregular behavior of EADs, (3) mechanisms by which chaotic EADs synchronize in large numbers of coupled cells in tissue to overcome source–sink mismatches, (4) how this synchronization process allows EADs to initiate triggers and generate mixed focal reentrant ventricular arrhythmias underlying PVT and TdP, and (5) therapeutic implications.

Keywords: Afterdepolarization, Arrhythmia, Chaos synchronization, Computer modeling, Nonlinear dynamics, Sudden cardiac death, Systems biology, Torsades de pointes, Triggered activity

Abbreviations: AP, action potential, APD, action potential duration, DI, diastolic interval, EAD, early afterdepolarization, PVC, premature ventricular complex, PVT, polymorphic ventricular tachycardia, TdP, torsades de pointes, VF, ventricular fibrillation, VT, ventricular tachycardia