Universally accepted mechanisms of induction, maintenance and perpetuation of AF are based mostly on hypothetical assumptions, simulation studies, experimental and clinical observations. However, there is general agreement that genesis and maintenance of AF requires complex interaction between trigger, perpetuator, and vulnerable atrial substrate. Important contributors to AF are shortened refractory period, regional variations of refractoriness (dispersion of repolarization) and conduction velocity, and increased ectopic or reentrant activity.6,62,63
Profound historical analysis of AF by Jalife6 highlighted the most important issues, controversies, and advances that have driven the field of investigation into AF mechanisms at any given time during the last âŒ100 years. In this elegant review we can find very important data regarding long competition of theories of AF genesis (focal, ectopic activity, reentry, circus movement, meandering spiral waves, scroll waves, multiple wavelets, vortices, turbulent activity, rotors, mother rotors, daughter rotors, etc.) postulated by prominent cardiologists and electrophysiologists â Lewis, Moe, Haissaquerre, Wiener, Rosenblueth, Allessie and many others.47,63,68
According to Jalife,69
it is conceivable that electrical impulses from the ectopic focus (e.g., localized in pulmonary vein inlets) may induce chaotic activation of the atria due to interaction with anatomical and/or functional barriers that leads to fragmentation of the depolarization front (daughter wavelets). Similarly, the spiral waves and scroll waves emitted by the rotor propagate through the cardiac muscle and interact with anatomical and functional obstacles, leading to fragmentation and new wavelet formation.70
Moe66 described the substrate of AF as a continuous activation of the atrial myocardium by several reentry circles that are not anatomically fixed, but spread and mingle in a seemingly chaotic pattern. The theoretical length of each reentry circle gives an expression of the minimal circumference and each depolarization must travel to avoid that the electrical impulse reaches its origin before this is again excitable; when refractoriness is short and conduction velocity is low, wavelength is also short.62,66,71
Thus, several reentry circles may exist simultaneously in the atria.62
Five or six reentry circles are associated with the stable AF, while a situation with fewer reentrant circles either converts to sinus rhythm, or degenerates into more reentry circles. 47,63
Reportedly, there are different number of propagating wavelets and rotors participating in AF and giving rise to the turbulent atrial activity. Some authors indicate single or small number of high-frequency sources,72-74
4-6 wavelets 75,76
and even 23-40 multiple circulating waves for arrhythmia sustenance.77
It is widely known that rotors may be responsible for the perpetuation of AF.6,66,69,70
The periodicity of rotations depends on wavelength (action potential duration), refractory period and conduction velocity, and these parameters are unstable, they shift in response to tempo of the electrical and structural remodeling.74,78
There are methodological difficulties in determining wavelength however some authors through indirect methods have established that it ranges from 5-7 cm up to 12-13 cm.74,79,80
Direct measurements from a computer model showed the wavelength of 5 cm.71
Electrical remodeling primarily shortens the refractory period and the action potential duration, while structural remodeling impedes propagation and hence decreases conduction velocity,74
electrical and structural remodeling both decrease the wavelength, thus potentially perpetuating AF.
The above mentioned mechanisms of AF genesis are consistent with the conceptual assumptions related to the atrial segmentation into ischemic and non-ischemic regions, thus resulting in electrophysiological disintegration of atria. Ischemia-dependent atrial electrophysiological behavior may be incorporated into the scenario depicted as IDCAF. Theoretically the sheer number of rotors, daughter rotors, wavelets and wavelength(s) are unstable and situation-dependent. As noted above, each borderline separating different atrial areas is not capable of producing/releasing the triggers. The main (dominant) borderline initially plays a key role in emanating focal/multifocal/reentrant triggers for AF. Obviously, this line â insidious arrhythmogenic substrate - contains the greatest potential of trigger(s) activity. All remaining borderlines being less important serve as a functional obstacle(s)/hurdle(s) where the rotors split into wavelets, daughter wavelets, i.e. into secondary, tertiary, etc. wavefronts. Here the wavelets most likely breakthrough, traverse, split, fragment, multiply, anchor, abrupt, die and/or extinguish. However, over time the role of the main borderline is taken over by the borderline(s) theretofore being less active or dormant/inactive; this may occur when the threshold of electrophysiological tension between conflicting areas is reached. So, all borderlines may demonstrate their activity in alternating manner and sooner or later become interchangeable. As a result of such uncontrolled game, the total chaos (bioelectrical instability, high-frequency oscillation activity, etc.) gradually and finally ingrains. Due to the mutual interactions, ischemically damaged and non-damaged myocardium do participate fundamentally in the relay-race carousel of arrhythmogenicity accompanied by the âfireworksâ at the separating borderlines. Any rotational direction of the driver â clockwise or counter-clockwise - is feasible. Regarding the localization, the size and geometric configuration of the ischemic region, the ectopic/reentrant pulses may propagate also centrifugally and/or centripetally. Most likely reentrant pulses move centrifugally inducing AF, while ectopic one â centripetally, thus evoking premature/extrasystolic beats. Different consequences may be expected in respect to which territory is traversed first (whether ischemic or non-ischemic) by the pulse emitted in the vulnerable substrate. It must be emphasized that the triggering pulse meets different, volatile and strongly defined medium â alternating environments with distinct electrophysiological characteristics being intersected by functional barriers. Taking into account the influence of gross structure and atrial myoarchitecture to the character of AF81,82
some different clinical manifestations of arrhythmia may occur and it could be related to the anatomical site of the vulnerable substrate â subendocardial, intramural, subepicardial, transmural. Finally, dislocation or migration of the separating borderlines also may take place and may influence the outbreak of AF, especially when the ischemic territory shrinks or expands. In any case, these peculiarities may act in concert with the previously declared phenomenon comparable with the vibrantly quiescent stroboscopic tuning.83
As long as AF is initiated by the principal borderline the arrhythmia is more amenable to the therapy (drugs, DC shock, ablation), however due to the development of alternating activities of the rest borderlinesâ arrhythmia becomes less controllable and finally uncontrollable. Most likely the dynamics of arrhythmia control is related to the parallel ongoing process of fibrotic changes with the advance of atrial remodeling.
Of course, AF remains multiethiological. However, the hypothetical presumptions presented here might be helpful to assert the processes taking place in the chain of the onset, maintenance and termination of AF. Hypothetically the ischemia is a mainstay and crucial contributing factor. However, there is a lack of convincing data to strongly argue the suggested approach. In the broad sense, the knowledge that different number of ischemic areas and their borderlines exist along with unstable number of rotors, wavelets, reentrant circles with their complex interactions might better explain the intrusive phenomenon of AF.
Analogical ischemia-based argumentation may be helpful in elucidating the pathogenesis of ventricular arrhythmias including fibrillation (except of syndromesâ associated with accessory conduction pathways or genetic origin).