Electrophysiological Changes of the Atrium in Patients with Lone Paroxysmal Atrial Fibrillation

Background: The "Pill-in-Pocket" (PIP) is an approach to atrial fibrillation (AF) where oral anti-arrhythmics at 75% to 100% of the normal daily dose, given as a single dose, is used to convert recent-onset AF. Pro-arrhythmic risk has limited this approach to patients without structural heart disease (SHD). Ranolazine is an anti-anginal agent, which inhibits the abnormal late Na+ channel current resulting in decreased Na+/Ca++ overload. This inhibits after-depolarizations and reduces pulmonary vein firing, which have been implicated in the initiation and propagation of AF. Ranolazine increases atrial refractoriness and has no known pro-arrhythmic affects. Ranolazine is routinely given to patients with SHD. The ability of Ranolazine to terminate AF in man has not been described but if useful could be a safer PIP agent with application in the presence or absence of SHD. We describe our experience using oral Ranolazine to convert new or recurrent AF.

Method: 2000 mg of ranolazine was administered to 35 patients with new (16 patients) or recurrent (19 patients) AF of at least 3 but not greater than 48 hours duration. Clinical features, echocardiographic data, and SHD were noted. Success was defined as restoring sinus rhythm within 6 hours of Ranolazine.

Results: All but 4 patients had some form of SHD. Twenty-five patients were in the hospital, 5 were in the office, and 5 were at home at the time Ranolazine was administered. Twenty-five of 35 patients converted to sinus rhythm. No pro-arrhythmic effects, hemodynamic instability, adverse rate effects, or perceived intolerance were noted. The 71% conversion rate was comparable to other reported PIP protocols and much higher than reported placebo conversion rates.

Conclusions: High dose oral Ranolazine shows utility as a possible safe agent to convert new or recurrent AF. Larger placebo-controlled studies would appear to be warranted.