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

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 cm²) 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.