Ionic and substrate mechanism of atrial fibrillation: rotors and the exitación frequency approach

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans, however its mechanisms are poorly understood and its therapy is often sub-optimal. This article reviews recent experimental, numerical and clinical data on dynamics of wave propagation during AF and its mechanistic link to ionic and structural properties of the atria. At the onset, the article presents numerical and optical mapping data suggesting that a presence of periodic source with increasingly high dominant frequency (DF) of excitation underlies observations of dispersion of local activation rate during AF. Further optical mapping studies in isolated normal sheep hearts in the presence of acetylcholine (ACh) reveals that rotors localized to the left atrium (LA) drive the arrhythmia and are faster than those in the right atrium (RA). Patch-clamp data from isolated cardiomycytes shows that the ACh-modulated potassium inward rectifier current is higher in the LA than in the RA which may explain the higher DFs and sensitivity of LA rotors to ACh compared with RA rotors. Following, the role of fibrosis in governing the propagation dynamics with a decrease in excitation frequency is presented in AF in failing sheep hearts and complex activation in cell cultures. Translation into the clinical setting is then discussed: DF distribution in patients with paroxysmal AF follows the LA-to-RA gradients found in the acute cholinergic AF of sheep hearts with highest DFs localized primarily to the posterior LA wall and pulmonary veins (PV) region; however in patients with persistent AF, the highest DFs localize mainly outside of the PVs region with possible implication on the outcome of ablation procedures. Next, intravenous injection of adenosine to patients in AF is demonstrated to result in further acceleration of high DF sites and suggests that reentrant activity, rather than triggered or automatic activity, maintains the arrhythmia. Finally, analysis of excitation during AF developed in patients post-cardiac surgery suggests a DF distribution similar to that of patients with paroxysmal AF with dependency on fibrosis as found in sheep failing hearts and cell cultures. In sum, the article presents data demonstrating the use of DF of excitation in linking wave propagation mechanisms to ionic and structural properties in both experimental and human AF.