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

Abstract

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).

Keywords: ablation; alcohol; atrial fibrillation; electrophysiology; lifestyle.

Conflict of interest statement

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.

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

Figures

Figure 1.

Consort Diagram for Trial Enrollment

Figure 2.. Proportion of Atrial Effective Refractory Periods (AERPs) that declined during alcohol and placebo infusions.

In Panel A., each row represents an individual participant, each column represents the AERP testing site (CSp denotes proximal coronary sinus; CSd denotes distal coronary sinus; HRA denotes high right atrium; RUPV denotes right upper pulmonary vein; LUPV denotes left upper pulmonary vein). Red denotes an AERP decline with the study infusion compared to baseline, blue denotes no decline, and white means testing was not performed. The hierarchy of these heat maps from top to bottom was dictated first by the proportion red, then red in order from the sites as listed from left to right. In Panel B., Box Plots represent the median (middle horizontal lines), 25th and 75th percentiles (boxes) and 1.5 times the interquartile ranges (error bars) of the percentages of AERP testing sites that declined during the infusion compared to baseline.

Central Illustration.. Change in Atrial Effective Refractory Period (AERP) with Study Infusion Compared to Baseline.

Black squares denote changes with the alcohol infusion, and white squares denote changes with the placebo infusion. Analyses utilized linear mixed models and took baseline AERP into account. Y error bars denote 95% confidence intervals.