Ventricular tachycardia: mechanistic insights derived from adenosine.

Abstract

A foundational concept in cardiac electrophysiology is that understanding the cellular mechanism of an arrhythmia provides essential insight for developing targeted therapeutic options. However, current clinical understanding of arrhythmogenic mechanisms other than re-entry is rudimentary, and the means by which to diagnose and differentiate these mechanisms are poorly defined. Grouping these mechanistic subtypes into broad and nonspecific categories, for example, non–re-entry or focal, further underscores our incomplete understanding of these arrhythmias. As the field of cardiac electrophysiology, like the rest of medicine, evolves toward the delivery of cell-based therapies, the need for a deeper understanding of clinical arrhythmia mechanisms and their arrhythmogenic cell lineages is apparent. One major difference between re-entrant and non– re-entrant ventricular tachycardia (VT) is that the electrophysiological substrate for re-entry is acquired during postnatal development and is due to anatomic insult (eg, ischemic heart disease or viral myocarditis), whereas the substrate for triggered activity is likely often acquired during embryological development, occurring independent of anatomic injury or structural heart disease.1,2 These dichotomous electrophysiological substrates, re-entry and non–re-entry, require tailored approaches to confirm diagnosis. In this review, we will elaborate on the development of a methodological approach for diagnosing non–re-entrant VT, which centers on the unique mechanism-specific properties of adenosine. This approach differs substantively from standard laboratory pacing methodologies used to validate the diagnosis of re-entrant arrhythmias and which are founded on the principles of entrainment.3 Adenosine is an endogenous nucleoside that exercises multiple regulatory functions that affect impulse generation and conduction, autonomic function, contractility, coronary vasodilation, and O2 supply–demand balance.4 Adenosine is rapidly inactivated as it is taken up by the cell through simple diffusion or a nucleoside transport system and is then deaminated to inosine or phosphorylated to adenosine monophosphate.5 The plasma half-life of adenosine is <1.5 s. …