It is not quite clear why atrial tissue becomes prone for arrhythmias. For a several decades this was mostly believed to be related to irritability of the heart tissue. The electrical impulses were thought to travel in waves that collide with each other and break down into several wavelets activating different part of the right and left upper chambers in a very irregular and chaotic fashion (Multiple Wavelet Theory). The role of specific triggers in the initiation of AFib is a discovery that is close to a decade old. Elevated pressures in the left atrium (valvular heart disease, hypertension, heart failure and obstructive sleep apnea etc) in conjunction with various genetic and environmental factors can make the muscular extensions of the left atria in to the pulmonary veins undergo arrhythmogenic changes. Thus, pulmonary veins start firing away and initiate arrhythmia. It was noted that in patients who have paroxysmal AFib, close to 94% of the arrhthmogenic foci were found to be in the pulmonary veins. The other structures like the left atrial appendage, coronary sinus, superior vena cava and the atrial body were also found to be responsible for focal activity in the remainder. The primary pathologic change seen in atrial fibrillation is the progressive fibrosis of the atria. This fibrosis is primarily due to atrial dilatation, however genetic causes and inflammation may have a cause in some individuals. This atrial scar can promote and perpetuate the triggered activity that comes from various pulmonary venous and non pulmonary venous foci. These areas of scar can act as the rotors that play an important role in sustaining the arrhythmia initiated by the foci.

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 valvular heart disease (such as mitral stenosis, mitral regurgitation, and tricuspid regurgitation), hypertension, and congestive heart failure. 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.

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. This process is not immediate, and experimental studies have revealed patchy atrial fibrosis may precede the occurrence of atrial fibrillation and may progress with prolonged durations of atrial fibrillation. 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.

Atrial fibrillation begets more atrial fibrillation. Mostly AFib begins as a paroxysmal arrhythmia with progressive burden and remodeling changes involving the atrial tissue it tends to become more persistent and then permanent. The more scar tissue forms in the atrial tissue more difficult it is to accomplish sinus rhythm.