Electropathological Substrate of Longstanding Persistent Atrial Fibrillation in Patients With Structural Heart Disease Epicardial Breakthrough

Background-During persistent atrial fibrillation (AF), waves with a focal spread of activation are frequently observed. The origin of these waves and their relevance for the persistence of AF are unknown. Methods and Results-In 24 patients with longstanding persistent AF and structural heart disease, high-density mapping of the right and left atria was performed during cardiac surgery. In a reference group of 25 patients, AF was induced by rapid pacing. For data analysis, a mapping algorithm was developed that separated the fibrillatory process into its individual wavelets and identified waves with a focal origin. During persistent AF, the incidence of focal fibrillation waves in the right atrium was almost 4-fold higher than during acute AF (median, 0.46 versus 0.12 per cycle per 1 cm(2) (25th to 75th percentile, 0.40 to 0.77 and 0.01 to 0.27; P<0.0001). They were widely distributed over both atria and were recorded at 46 +/- 18% of all electrodes. A large majority (90.5%) occurred as single events. Repetitive focal activity (>3) happened in only 0.8%. The coupling interval was not more than 11 ms shorter than the average AF cycle length (P=0.04), and they were not preceded by a long interval. Unipolar electrograms at the site of origin showed small but clear R waves. These data favor epicardial breakthrough rather than a cellular focal mechanism as the underlying mechanism. Often, conduction from a site of epicardial breakthrough was blocked in 1 or more directions. This generated separate multiple wave fronts propagating in different directions over the epicardium. Conclusions-Focal fibrillation waves are due to epicardial breakthrough of waves propagating in deeper layers of the atrial wall. In patients with longstanding AF, the frequency of epicardial breakthroughs was 4 times higher than during acute AF. Because they provide a constant source of independent fibrillation waves originating over the entire epicardial surface, they offer an adequate explanation for the high persistence of AF in patients with structural heart disease. (Circulation. 2010;122:1674-1682.)