Atrial fibrillation pathophysiology

Overview
The primary pathologic or structural change observed in patients with atrial fibrillation is progressive fibrosis of the atria. This fibrosis is primarily due to atrial dilatation, however genetic causes and inflammation may also play a role in some individuals. There are other functional processes that contribute to the development and persistence of atrial fibrillation including hemodynamic stress (stretching of the atrium), atrial ischemia, activation of the neurohormonal system, ectopic activity in the pulmonary vein, multiple wavelets of electrical activity in the atrium, and catecholamine excess. The mechanism in most patients is likely to be multifactorial.

Dilation of the Atria
Dilatation of the atria can be due to almost any structural abnormality of the heart that can cause a rise in the intra-cardiac pressures. This includes:
 * Hypertension, most likely the most common cause of atrial dilation in the current era
 * Valvular heart disease (such as mitral stenosis, mitral regurgitation, and tricuspid regurgitation)
 * Congestive heart failure
 * Coronary Artery Bypass Graft Surgery

Once dilatation of the atria has occurred, this begins a chain of events that leads to the activation of the renin aldosterone angiotensin system (RAAS) and subsequent increase in matrix metaloproteinases and disintegrin, which leads to atrial remodeling and fibrosis, with loss of atrial muscle mass.

Inflammation of the Atria
Any inflammatory state that affects the heart can cause fibrosis of the atria. This is typically due to sarcoidosis but may also be due to autoimmune disorders that create autoantibodies against myosin heavy chains. Mutation of the lamin AC gene is also associated with fibrosis of the atria that can lead to atrial fibrillation.

Fibrosis of the Atria
Patchy atrial fibrosis may precede the occurrence of atrial fibrillation and the magnitude of fibrosis may progress with a prolonged duration of atrial fibrillation.

Fibrosis of the SA Node
Fibrosis is not limited to the muscle mass of the atria, and may occur in the sinus node (SA node) and atrioventricular node (AV node), correlating with sick sinus syndrome. Prolonged episodes of atrial fibrillation have been shown to correlate with prolongation of the sinus node recovery time, suggesting that dysfunction of the SA node is progressive with prolonged episodes of atrial fibrillation.

Ectopic Foci in the Pulmonary Vein
Younger patients with paroxysmal atrial fibrillation will sometimes have ectopic foci of electrical activity in the pulmonary vein that can be ablated. There are cells in the pulmonary vein whose electrical properties resemble those of the myocytes of the atrium. These patients generally have high grade ectopic activity on Holter monitoring. While the pulmonary vein is a common source of these ectopic foci, there may also be foci present in the atrium itself. While the pulmonary vein may function as a trigger, it is the heterogeneity of conduction that may sustain the atrial fibrillation.

The Multiple Wavelet Phenomenon
It has been hypothesized that if there is a greater atrial mass, delayed atrial conduction times, and a shortened atrial refractory period, then this promotes the propagation of wavelets. This hypothesis is supported by the observation that prolongation of intra-atrial conduction times is associated with a recurrence of atrial fibrillation.