Importance of atrial surface area and refractory period in sustaining atrial fibrillation: testing the critical mass hypothesis

Abstract

Objective: The critical mass hypothesis for atrial fibrillation (AF) was proposed in 1914; however, there have been few studies defining the relationship between atrial surface area and AF. This study evaluated the effect of tissue area and effective refractory period (ERP) on the probability of sustaining AF in an in vivo model.

Methods: Domestic pigs (n = 9) underwent median sternotomy. Epicardial activation maps were constructed from bipolar electrograms recorded from form-fitting electrode templates placed on the atria. Baseline ERPs were determined. ERP was lowered with a continuous infusion of acetylcholine (0.005-0.04 mg/Kg/min) until AF could be sustained after burst pacing. The atria were sequentially partitioned using bipolar radiofrequency ablation. ERPs were lowered using acetylcholine until AF could be sustained in each subdivision of atrial tissue. Each subdivision was further divided until AF was no longer inducible. At study completion, the heart was excised and the surface area of each section was measured.

Results: Over a range of ERPs from 75 to 250 ms, the probability of AF was correlated with increasing tissue area (range, 19.5-105 cm(2)) and decreasing ERP. Logistic regression analysis identified shorter ERP (P < .001) and larger area (P = .006) as factors predictive of an increased probability of sustained AF (area under the curve of the receiver-operator characteristic = 0.878).

Conclusions: The probability of sustained AF was significantly associated with increasing tissue area and decreasing ERP. These data may lead to a greater understanding of the mechanism of AF and help to design better interventional procedures.

Keywords: 24; AF; CT; ECG; ERP; atrial fibrillation; computed tomography; effective refractory period; electrocardiogram.

Figure 1

The lesion set used to subdivide the atrium. After ablating around the pulmonary veins as a starting point, the atria were divided into two sections with lines 1a and 1b, taking advantage of the natural conduction block of the aortic and mitral annuli. The right atrium was further divided with lines 1 and 2, such that the area paced (marked by an asterisk) was progressively smaller after each iteration. On the left subdivision, line 2 removed the area of the left atrial appendage, and a final line (3) subdivided the remaining tissue area around the pacing electrode.

Figure 2

Dose-response relationship of normalized ERP vs. acetylcholine dose at peak effect. ERP was normalized to the ERP measured prior to administration of acetylcholine. As the dose of acetylcholine increased, the measured ERP decreased (p = 0.015).

Figure 3

Time course of ERP, normalized to initial value at time zero before infusion of acetylcholine at 0.01 mg/kg/min. After 5 minutes, the ERP decreased to a stable level. At time 20 minutes, the infusion was turned off, and ERP recovered to baseline level within 5 minutes.

Figure 4

The probability of sustained atrial fibrillation (y-axis) is plotted against ERP (x-axis) and surface area (z-axis). As area decreased (dark grey to white), the probability of sustained AF decreased. As ERP increased, the probability of sustained AF decreased.

Figure 5

The predictive model of the sustainability of atrial fibrillation is plotted. For each range of ERP, the probability of sustained atrial fibrillation (y-axis) increased with increasing surface area (x-axis). A line is plotted for specific values of ERP. As ERP increases, the probability of sustained AF decreases. The area under the curve of the receiver operating characteristic curve is 0.878, and the McFadden-Rho² was 0.358.