Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and associated with severe remodelling of electrical and structural properties of the atria, which contributes to the high recurrence rate in AF patients. While much research has been done on the pathomechanisms of AF onset, less is known about the exact time course and reversibility of AF-associated atrial remodelling processes. To determine the probability of maintenance of sinus rhythm (SR) after cardioversion of AF patients, development and reversibility of structural and electrical changes have to be assessed on a temporal scale. Regarding the electrical atrial remodelling, upregulation of the two-pore domain potassium channel TASK-1 is known as an important mechanism causing action potential shortening seen in AF patients.

Purpose: To investigate the time course and reversibility of AF-associated electrical and structural remodelling on a clinical, cellular and molecular level.

Methods: An established large-animal model of AF was used to investigate structural and functional aspects of atrial remodelling after different time periods of AF. Clinical parameters like atrial refractory times and atrial diameters were determined at baseline and after the desired period of AF induction. After extraction of the heart, action potentials (APs) and ion currents were measured from isolated atrial cardiomyocytes (CM) using the patch-clamp technique and compared to baseline. The pig model was further developed to investigate the reversibility of observed changes. After a certain AF period, pigs were electrically cardioverted and had a SR recovery period before the same parameters were investigated.

Results: After four weeks of AF, APD₉₀ was reduced by 25.8 %. Extending the AF period to eight weeks caused an even stronger APD₉₀ reduction by one-third, compared to SR controls.  In line with this, TASK-1 current density was strongly upregulated in the AF groups. Those results were in line with significant changes of the atrial effective refractory period (AERP), an important clinical parameter. At baseline, AERP_S1=400 ms averaged out at 186 ms, whereas it was reduced to 141 ms after eight weeks of AF. Addressing the reversibility of those changes, following an eight weeks long SR recovery period, AERP baseline values were almost restored. At the same time, APD₉₀ shortening was partially reversed. Additionally, indication of reversibility of AF-associated remodelling was also observed on a structural level. Strong dilatation of the atria was shown after eight weeks of AF using echocardiography, while atrial diameters became smaller again after restoration of SR.

Conclusion: AF-associated electrical and structural remodelling processes seem to be partially reversible after restoration and maintenance of SR.