Mechanisms of Atrial Fibrillation

Abstract

Summary Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. However its mechanisms are poorly understood and AF 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 outset, we review numerical and optical mapping data suggesting that the sustained activity of periodic drivers (rotors) with exceedingly high dominant frequencies (DF) of excitation underlies the spatial dispersion and irregularity of activation rates that characterize AF. We show how optical mapping of the fibrillating atria in isolated normal sheep hearts has revealed that the rotors tend to localize in the left atrium (LA). We then discuss exciting new data in the sheep model of tachypacing induced AF demonstrating that the DF of paroxysmal AF episodes increases progressively over days or weeks during the transition to persistent AF (PeAF) and that the rate of the DF increase predicts the onset of PeAF. The data show that the DF increase during the transition may be explained by rotor acceleration secondary to upregulation of IK1 and downregulation of ICaL. The article concludes with a discussion on how translation of experimentally derived knowledge on the behavior and frequency of rotors may find its way into the clinic. We focus on studies in which the analysis of the spatial patterns of DF distribution in the atria of patients with paroxysmal vs persistent has increased our understanding of human AF and how that knowledge might contribute to improve the outcome of AF ablation procedures.

Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity

“…The in-silico observation in this study that ablation based on DF terminated AF suggests that mother rotors are very likely a mechanism of AF maintenance considering that the area of highest DF coincides with the mother rotor area. This antiarrhythmic effect of DF-based ablation is consistent with the results of several studies reported in the literature [ 11 ].…”

“…Mother rotors have been considered a mechanism of AF initiation and maintenance for the past few decades, though the concept was initially proposed a century ago [ 8 – 11 ]. Much experimental evidence and in silico validations have supported the role of mother rotors in AF [ 8 – 10 ].…”

“…The term “mother rotor” is used when wavelets are generated from the breakup of the wavefronts of the rotor [ 7 , 8 ]. The mother rotor, which is stable and induces fibrillatory conduction, is considered a mechanism responsible for the maintenance of AF [ 8 – 11 ]. An example of a temporal definition of mother rotor is the one used by Keldermann et al [ 12 ], which defines the duration of a ventricular fibrillation (VF) mother rotor as at least 5 s. Both temporal and spatial definitions of the mother rotor would help quantify the results of studies investigating the mechanism of cardiac fibrillation.…”

Hyperthyroidism, but not hypertension, impairs PITX2 expression leading to Wnt-microRNA-ion channel remodeling

“…It is well-established that the onset of an AF episode triggers subsequent and more severe AF episodes, leading to electrical and structural remodeling of the diseased heart, a condition quoted as “AF begets AF” [ 17 ]. Electrical remodeling involves progressive changes in the cardiac electrical properties, leading to early afterdepolarization, delayed afterdepolizations and/or changes in the action potential duration configuration [ 17 ], culminating thus in rotor formation [ 18 ]. In this context, a pivotal role of reactive oxidative stress has been recently reported [ 19 – 20 ].…”

A New Efficient Method for Detecting Phase Singularity in Cardiac Fibrillation

“…For instance, a stable mother rotor is known to induce fibrillatory conduction, and thereby is a key for sustaining AF [5, 7, 27]. Haissaguerre et al [28] suggested that organized and discrete sources of AF exist in human AF patients, and showed that a local radiofrequency ablation could terminate AF.…”