A meta-analysis for efficacy and safety evaluation of transcatheter left atrial appendage occlusion in patients with nonvalvular atrial fibrillation
BACKGROUND It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it in the case of a focal mechanism. METHODS AND RESULTS Thirty-three patients were studied during AF (21 paroxysmal, 12 persistent) using recordings from each pulmonary vein-left atrial junction (PV-LAJ), high right atrium, and coronary sinus. DFs were determined during baseline and peak adenosine effect. In paroxysmal AF, adenosine increased maximal DF at each region compared with baseline (PV-LAJ, 8.03+/-2.2 versus 5.7+/-0.8; high right atrium, 7+/-2.2 versus 5.4+/-0.7; coronary sinus, 6.6+/-1.1 versus 5.3+/-0.7 Hz; P=0.001) and increased the left-to-right DF gradient (P=0.007). In contrast, in persistent AF, adenosine increased DF only in the high right atrium (8.33+/-1.1 versus 6.8+/-1.2 Hz; P=0.004). In 4 paroxysmal AF patients, real-time DF mapping of the left atrium identified the highest DF sites near the PV-LAJ, where adenosine induced an increase in DF (6.7+/-0.29 versus 4.96+/-0.26 Hz; P=0.008). Finally, simulations demonstrate that the frequency of reentrant drivers accelerates proportionally to the adenosine-modulated inward rectifier potassium current. CONCLUSIONS Adenosine accelerates drivers and increases frequency differently in paroxysmal compared with persistent human AF. The results strongly suggest that AF is maintained by reentrant sources, most likely located at the PV-LAJ in paroxysmal AF, whereas non-PV locations are more likely in persistent AF.