Does AF Beget AF Based on Mechanical Compression of Atrial Blood Vessels Causing Ischemia?

The concept that an episode of atrial fibrillation (AF) creates conditions that foster more AF was introduced by Wijffels, Allessie, and colleagues in 1995 in their publication entitled “Atrial Fibrillation Begets Atrial Fibrillation: A Study in Awake Chronically Instrumented Goats.”¹ Since then, much has been learned about the immediate electrical and longer term structural remodeling that occurs during AF, which can ultimately become irreversible. The immediate effects of AF can easily be demonstrated in humans in the EP lab. Repeated efforts to induce AF with rapid pacing are commonly followed by longer and longer episodes of AF that eventually do not terminate spontaneously. Studies by Daoud et al in the mid 1990s showed that calcium channel blockade with verapamil can attenuate the acute shortening of atrial refractory periods that occur after a brief episode of induced AF, suggesting that calcium overload from the tachycardia plays a role.² Evidence of the impact of longer episodes of AF on the atrium includes the demonstration of atrial scar in patients with longstanding persistent AF, and the high likelihood of recurrence after cardioversion or ablation. In addition, studies of post conversion atrial mechanical dysfunction have shown that atrial mechanical contraction is slow to recover after restoration of sinus rhythm with a time course that is proportional to the duration of the AF episode. 

Although the impact of rapid ventricular rates on the ventricular myocardium during AF and the risk of a tachycardia-induced cardiomyopathy are commonly considered, the mechanical impact of AF on the atrial muscle itself receives less attention. However, there is increasing evidence that the rapid atrial rates during AF lead to atrial ischemia and that an atrial supply-demand mismatch may be the critical link between rapid atrial rates and atrial remodeling. In a study by van Bragt et al in the May 2015 issue of HeartRhythm, the dynamic regulation of atrial coronary flow was characterized in pigs using Doppler flow probes placed around the left atrial and ventricular branches of the circumflex artery.³ The experiments showed that only 2% of total left atrial flow occurs during atrial systole, and that atrial coronary flow is impeded by atrial contraction and not by elevations in left atrial chamber pressure. A prominent hyperemic phase that was demonstrated following termination of AF supported their hypothesis that AF results in a significant supply-demand mismatch in the atrial tissue. The same group has also demonstrated an increase in lactate production.

Much has been learned about why AF begets AF, but interventions that have been based on that knowledge have yet to have a large clinical impact on patients with recurrent AF. These experimental data from Maastricht University suggest that the rapid rates during AF may result in at least some of the atrial electrical and structural remodeling that occurs during AF on the basis of mechanical systolic compression of atrial blood vessels leading to a supply-demand mismatch and inadequate blood supply. This information may be useful in the development of novel therapies to interrupt the natural progression from paroxysmal to persistent AF.

References

1. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats. Circulation. 1995;92:1954-1968.
2. Daoud EG, Knight BP, Weiss R, et al. Effect of verapamil and procainamide on atrial fibrillation-induced electrical remodeling in humans. Circulation. 1997;96:1542-1550.
3. Van Bragt KA, Nasrallah HM, Kuiper M, et al. Dynamic regulation of atrial coronary blood flow in healthy adult pigs. Heart Rhythm. 2015;12:991-1000.