From the Guidelines
Delayed afterdepolarizations (DADs) are abnormal electrical events that occur after complete membrane repolarization, triggered by intracellular calcium overload, and can lead to life-threatening arrhythmias, such as ventricular tachycardia, particularly in conditions like digoxin toxicity, catecholaminergic polymorphic VT, and heart failure. These events are characterized by spontaneous calcium release from the sarcoplasmic reticulum, which activates a transient inward current driven predominantly by the sodium–calcium exchange current, potentially resulting in a triggered action potential if the membrane depolarization is sufficiently large 1. Key factors contributing to the development of DADs include:
- Tachycardia
- Catecholamines
- Hypokalemia
- Digoxin toxicity
- Cardiac hypertrophy
- Heart failure DADs are considered an important trigger of ventricular arrhythmias in various clinical settings, and their mechanism involves the activation of the inward sodium current, leading to unexpected action potentials 1. Understanding the role of DADs in initiating arrhythmias is essential for the diagnosis and management of patients with ventricular arrhythmias, particularly those with underlying conditions that predispose to intracellular calcium overload 1.
From the Research
Definition of Delayed Afterdepolarization (DAD)
- Delayed afterdepolarizations (DADs) are a type of afterdepolarization that occurs after repolarization is complete 2.
- DADs are caused by an elevation of Ca2+ in the sarcoplasmic reticulum (SR), which leaks into the myoplasm through Ca2+ release channels controlled by ryanodine receptors (RyR2) during diastole 2.
- The Na+ -Ca2+ exchanger extrudes elevated diastolic Ca2+ from the cell in exchange for Na+, generating an inward current that causes DADs 2.
Characteristics of DADs
- DAD amplitude increases with decreasing cycle length, causing triggered activity during an increase in heart rate or during programmed electrical stimulation (PES) 2.
- The coupling interval of the first triggered impulse is directly related to the initiating cycle length 2.
- DADs depend on the diastolic potential, and hyperpolarizing current can decrease DADs and render them subthreshold 3.
- Depolarizing current can increase the DAD amplitude 3.
Role of DADs in Arrhythmias
- DADs can generate both triggers and a vulnerable substrate promoting reentry in cardiac tissue 4.
- Random DADs can self-organize to generate both an arrhythmia trigger and a vulnerable substrate simultaneously in cardiac tissue as a result of gap junction coupling 4.
- DADs can cause triggered activity, unidirectional conduction block, and reentry, and the probability of these behaviors is enhanced by reduced sodium channel availability, reduced gap junction coupling, increased tissue heterogeneity, and less synchronous DAD latency 4.