Atrial fibrillation (AF) shares strong associations with other cardiovascular diseases, such as heart failure, coronary artery disease (CAD), valvular heart disease, diabetes mellitus, and hypertension. These factors have been termed upstream risk factors, but the relationship between comorbid cardiovascular disease and AF is incompletely understood and more complex than this terminology implies. The exact mechanisms by which cardiovascular risk factors predispose to AF are not understood fully but are under intense investigation. Catecholamine excess, hemodynamic stress, atrial ischemia, atrial inflammation, metabolic stress, and neurohumoral cascade activation are all purported to promote AF.
Because diabetes mellitus and obesity are increasing in prevalence and are associated with an elevated risk of AF, Fontes et al examined whether insulin resistance is an intermediate step for the development of AF. In a community-based cohort that included 279 patients who developed AF within 10 years of follow-up, no significant association was observed between insulin resistance and incident AF.
Although the precise mechanisms that cause atrial fibrillation are incompletely understood, AF appears to require both an initiating event and a permissive atrial substrate. Significant recent discoveries have highlighted the importance of focal pulmonary vein triggers, but alternative and nonmutually exclusive mechanisms have also been evaluated. These mechanisms include multiple wavelets, mother waves, fixed or moving rotors, and macro-reentrant circuits. In a given patient, multiple mechanisms may coexist at any given time. The automatic focus theory and the multiple wavelet hypothesis appear to have the best supporting data.
A focal origin of AF is supported by several experimental models showing that AF persists only in isolated regions of atrial myocardium. This theory has garnered considerable attention, as studies have demonstrated that a focal source of AF can be identified in humans and that isolation of this source can eliminate AF.
The pulmonary veins appear to be the most frequent source of these automatic foci, but other foci have been demonstrated in several areas throughout the atria. Cardiac muscle in the pulmonary veins appears to have active electrical properties that are similar, but not identical, to those of atrial myocytes. Heterogeneity of electrical conduction around the pulmonary veins is theorized to promote reentry and sustained AF. Thus, pulmonary vein automatic triggers may provide the initiating event, and heterogeneity of conduction may provide the sustaining conditions in many patients with AF.
The multiple wavelet hypothesis proposes that fractionation of wave fronts propagating through the atria results in self-perpetuating "daughter wavelets." In this model, the number of wavelets is determined by the refractory period, conduction velocity, and mass of atrial tissue. Increased atrial mass, shortened atrial refractory period, and delayed intra-atrial conduction increase the number of wavelets and promote sustained AF. This model is supported by data from patients with paroxysmal AF demonstrating that widespread distribution of abnormal atrial electrograms predicts progression to persistent AF. Intra-atrial conduction prolongation has also been shown to predict recurrence of AF. Together, these data highlight the importance of atrial structural and electrical remodeling in the maintenance of AF—hence the phrase "atrial fibrillation begets atrial fibrillation."
Source : http://emedicine.medscape.com/article/151066-overview#a0104