Abstract 2447: Isoproterenol, but Not Vagomimetic Agents or Burst Pacing, Initiates Human Atrial Fibrillation by Steepening Action Potential Duration Restitution
Background: Isoproterenol, adenosine, and rapid pacing are known to induce atrial fibrillation (AF), yet via unclear mechanisms. We set out to determine if they steepen left atrial (LA) action potential duration (APD) restitution and thus provide a mechanism for AF induction.
Methods: We studied 21 patients with AF (10 persistent) and 5 controls. We performed single extrastimulus pacing in the LA to measure APD restitution slope (fig 1A⇓) with monophasic action potential (MAP) catheters. We then infused isoproterenol (n=10) or adenosine (n=6), or performed rapid pacing (n=13) and remeasured APD restitution prior to AF initiation.
Results: Patients were of age 62±14 y; LA diameter 43±6 mm. Isoproterenol increased APD restitution slope in patients with AF (1.09±0.62 to 1.79±0.59, p=0.02, fig 1B⇓). APD restitution slope changed from <1 to >1 in all persistent AF (0.55±0.29 to 1.81±0.88, p=0.01), but remained >1 in all paroxysmal AF (1.52±0.45 to 1.77±0.30, p=NS) and <1 in all controls (0.58±0.37 to 0.82±0.12, p=0.03 vs AF). Neither adenosine (1.09±0.62 to 1.01±0.52, p=NS) nor burst pacing (1.09 to 1.05±0.33, p=NS) increased max APD restitution in patients with AF. A total of 18 episodes of AF were observed; always in the setting of steep APD restitution with isoproterenol (fig 1C⇓), but rarely with burst pacing (3 of 11, p<0.026 versus isoproterenol).
Conclusions: Isoproterenol steepens maximum APD restitution, which may explain its pro-fibrillatory action in patients with persistent AF. Conversely, adenosine and burst pacing may initiate AF via alternative mechanisms involving focal triggers rather than reentry. These results may help guide new strategies to prevent AF initiation.