A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Alcohol to Assess Changes in Atrial Electrophysiology.

OBJECTIVES

This study sought to identify acute changes in human atrial electrophysiology during alcohol exposure.

BACKGROUND

The mechanism by which a discrete episode of atrial fibrillation (AF) occurs remains unknown. Alcohol appears to increase the risk for AF, providing an opportunity to study electrophysiologic effects that may render the heart prone to arrhythmia.

METHODS

In this randomized, double-blinded, placebo-controlled trial, intravenous alcohol titrated to 0.08% blood alcohol concentration was compared with a volume and osmolarity-matched, masked, placebo in patients undergoing AF ablation procedures. Right, left, and pulmonary vein atrial effective refractory periods (AERPs) and conduction times were measured pre- and post-infusion. Isoproterenol infusions and burst atrial pacing were used to assess AF inducibility.

RESULTS

Of 100 participants (50 in each group), placebo recipients were more likely to be diabetic (22% vs. 4%; p = 0.007) and to have undergone a prior AF ablation (36% vs. 22%; p = 0.005). Pulmonary vein AERPs decreased an average of 12 ms (95% confidence interval: 1 to 22 ms; p = 0.026) in the alcohol group, with no change in the placebo group (p = 0.98). Whereas no statistically significant differences in continuously assessed AERPs were observed, the proportion of AERP sites tested that decreased with alcohol (median: 0.5; interquartile range: 0.6 to 0.6) was larger than with placebo (median: 0.4; interquartile range: 0.2 to 0.6; p = 0.0043). No statistically significant differences in conduction times or in the proportion with inducible AF were observed.

CONCLUSIONS

Acute exposure to alcohol reduces AERP, particularly in the pulmonary veins. These data demonstrate a direct mechanistic link between alcohol, a common lifestyle exposure, and immediate proarrhythmic effects in human atria. (How Alcohol Induces Atrial Tachyarrhythmias Study [HOLIDAY]; NCT01996943).

Informations de copyright

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures This study was funded by National Institute of Alcohol Abuse and Alcoholism grant R01AA022222 (to Dr. Marcus). Technical support for the alcohol clamp procedure, including the Computer-Assisted Infusion Software (CAIS), was provided by Dr. Martin Plawecki, Dr. Sean O'Connor, Mr. Victor Vitvitskiy, and Mr. James Hays, Indiana Alcohol Research Center, Indiana University School of Medicine (P60 AA006711). Dr. Marcus has received research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute, Medtronic, Eight, Jawbone, and Baylis; and is a consultant and holds equity interest in InCarda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.