Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation

Early (EAD) and delayed (DAD) afterdepolarizations-induced triggered activity is capable of initiating and maintaining cardiac arrhythmias. EAD-induced triggered responses are traditionally thought to be involved in the generation of ventricular arrhythmias under long QT conditions and are precipitated by bradycardia or long pauses. In contrast, DAD-induced triggered activity commonly underlies arrhythmias precipitated by tachycardia. Spontaneous release of calcium from the sarcoplasmic reticulum (SR) secondary to cellular calcium overload induces DADs and some forms of EADs. Recent studies from our laboratory have uncovered a novel mechanism giving rise to triggered activity, termed "late-phase 3 EAD," which combines properties of both EAD and DAD, but has its own unique character. Late-phase 3 EAD-induced triggered extrasystoles represent a new concept of arrhythmogenesis in which abbreviated repolarization permits "normal SR calcium release" to induce an EAD-mediated closely coupled triggered response, particularly under conditions permitting intracellular calcium loading. This review briefly describes the mechanisms and properties of late-phase 3 EADs, how they differ from conventional EADs and DADs, as well as their role in the initiation of cardiac arrhythmias, such as atrial fibrillation.