Alcohol and Arrhythmias: State-of-the-Art Review (JACC EP 2023)

JACC: CLINICAL ELECTROPHYSIOLOGY
VOL. 9, NO. 2, 2023
ª 2023 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
STATE-OF-THE-ART REVIEW
Alcohol and Arrhythmias
Christopher X. Wong, MBBS, MS, PHD,a,b Samuel J. Tu, MBBS (HONS),b Gregory M. Marcus, MD, MASa
ABSTRACT
The association between alcohol consumption and abnormalities of heart rate and rhythm has long been recognized.
Significant attention has focused on the risk of atrial fibrillation (AF) and sudden cardiac death (SCD) with excessive
alcohol intake. Recent studies have advanced our understanding of these relationships and provided additional
insights into potentially arrhythmogenic mechanisms. However, considerable uncertainty remains, such as the level of
consumption at which harm begins and whether alcohol plays a role in other arrhythmias. This review characterizes the
spectrum of conduction abnormalities and heart rhythm disorders in relation to alcohol consumption. In addition, it
discusses the latest epidemiologic and experimental evidence, the potential importance of beverage type and constituent
ingredients, and conflicting information on drink definitions, thresholds, and recommendations.
(J Am Coll Cardiol EP 2023;9:266–279) © 2023 by the American College of Cardiology Foundation.
T
he association between alcohol consumption
disorders in relation to alcohol consumption (Central
and abnormalities of heart rate and rhythm
Illustration). In addition, we discuss the latest epide-
has long been recognized. Descriptions of
miologic and experimental evidence, the potential
the deleterious effects of long-term alcohol excess
importance of beverage type and constituent ingredi-
on cardiac structure and function that predisposes
ents, and conflicting information on drink definitions,
to sudden cardiac death (SCD) are documented from
thresholds, and recommendations.
as early as the 19th century. 1 However, it was not until the 1970s that widespread recognition of a harmful
OVERVIEW OF ALCOHOL CONSUMPTION,
relationship
DEFINITIONS, AND BEVERAGE TYPES
between
alcohol
and
arrhythmias
occurred, with popularization of the term “holiday
heart.” 2 A significant body of literature now exists
Alcohol consumption remains prevalent in our soci-
on the arrhythmogenic effects of heavy alcohol
ety as it has for thousands of years, with current or
intake, particularly with regard to atrial fibrillation
former drinkers comprising more than one-half
(AF) and SCD. Importantly, these data need to be dis-
(55.5%) of the worldwide population. 3 Consumption
cussed in the context of the continuing scientific and
is considerably higher in some regions such as the
public controversy on whether light alcohol con-
United States, where 69.5% of adults reported drink-
sumption is harmful, neutral, or even potentially
ing in the past year.4 Current drinkers consume an
beneficial
and
average of 32.8 g of alcohol per day.3 However, there
arrhythmic point of view; this is particularly relevant
are substantial variations and a lack of awareness of
because alcohol is likely to remain ubiquitous in our
how this translates into standard drink definitions
society. In this review, we characterize the spectrum
across different areas. For example, in the United
of
States, 1 standard drink equates to 14 g of alcohol,
from
conduction
a
general
abnormalities
cardiovascular
and
heart
rhythm
From the aDepartment of Electrophysiology, Division of Cardiology, University of California-San Francisco, San Francisco,
California, USA; and the bCentre for Heart Rhythm Disorders (CHRD), University of Adelaide and Royal Adelaide Hospital,
Adelaide, Australia.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.
Manuscript received September 8, 2022; accepted October 12, 2022.
ISSN 2405-500X/$36.00
https://doi.org/10.1016/j.jacep.2022.10.023
Wong et al
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HIGHLIGHTS
The potential impact of alcohol on arrhythmias continues to be an active area
of interest for both the medical community and the general public.
Although excessive consumption is likely
to cause more AF, AFL, and SCD, the influence of alcohol on other arrhythmias,
including cardiac ectopy, ventricular
tachyarrhythmias, and bradyarrhythmia
is uncertain.
The effects of regular light consumption
of up to 1 drink a day remain unknown,
with conflicting evidence that this may
both increase and decrease the risk of
arrhythmias.
Other ongoing areas of uncertainty
include whether thresholds of alcohol
amount exist, the role of beverage type,
and arrhythmogenic mechanisms.
267
Alcohol and Arrhythmias
whereas in the United Kingdom, 1 standard
ABBREVIATIONS
drink comprises 8 g of alcohol; in contrast,
AND ACRONYMS
the World Health Organization definition is
10 g of alcohol. 5 This variation represents a
challenge for both undertaking and communicating the findings of alcohol research.
Globally,
the
most
consumed
alcoholic
beverage type is spirits (44.8%), followed by
beer (34.3%) and wine (11.7%).3 However,
geographic differences similarly exist in
beverage type consumption; in the Americas
and Europe, for example, beer is most often
consumed (53.8% and 40.0%, respectively).3
Debate continues about whether specific
AF = atrial fibrillation
AFL = atrial flutter
PAC = premature atrial
contraction
PVC = premature ventricular
contraction
SCD = sudden cardiac death
SVT = supraventricular
tachycardia
VF = ventricular fibrillation
VT = ventricular tachycardia
beverage types may be more or less harmful regarding
certain cardiovascular outcomes. Specifically, it has
been postulated that polyphenols such as resveratrol
found in wine may confer benefit, although this remains controversial.6 However, there currently are
fewer data on beverage-specific associations of alcohols with arrhythmias, discussed in subsequent sections, as compared with ischemic heart disease and
other cardiovascular conditions.7
C ENTR AL I LL U STRA T I O N Risk of Different Arrhythmias With Alcohol Use and Possible Arrhythmogenic
Mechanisms
Wong CX, et al. J Am Coll Cardiol EP. 2023;9(2):266–279.
AF ¼ atrial fibrillation; AFL ¼ atrial flutter; CD ¼ conduction disease; PAC ¼ premature atrial contraction; PVCs ¼ premature ventricular contraction; SCD ¼ sudden
cardiac death; SND ¼ sinus node dysfunction; SVT ¼ supraventricular tachycardia; VF ¼ ventricular fibrillation; VT ¼ ventricular tachycardia.
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Alcohol and Arrhythmias
ALCOHOL AND ATRIAL ARRHYTHMIAS
F I G U R E 1 Odds of Any Real-Time, Self-Reported Drinking
Event Before an AF Episode
PREMATURE
ATRIAL
CONTRACTIONS. Premature
atrial contractions (PACs) are common and are often
considered benign. However, not only can they be
symptomatic for some patients and a trigger for sustained arrhythmias, but there is also a continuous
association of increasing PAC counts with AF, stroke,
heart failure, and death.8 Although alcohol reduction
is often recommended to patients with symptomatic
PACs, there is relatively little evidence to support this
practice. In a Swiss cohort of 1,742 individuals,
greater alcohol consumption was not associated with
increasing PAC count. 9 Similarly, among 1,392 participants
in
the
Cardiovascular
Health
Study,
increasing alcohol intake was not associated with
PACs (increase per unit 3%; 95% CI: 2% to 8%;
Error bars denote 95% CIs. Reproduced with permission from
Marcus et al.24 AF ¼ atrial fibrillation.
P ¼ 0.30). 10 In the MunichBREW study (Munich Beer
Related Electrocardiogram Workup Study), which
investigated the association of acute alcohol intoxi-
alcohol may be less influential on SVT compared with
cation using breath alcohol concentration on ar-
other arrhythmias such as AF. For example, we found
rhythmias
handheld
that patients with SVT were substantially less likely
electrocardiogram in 3,028 patrons of the 2015
to report alcohol as an arrhythmia trigger compared
Munich Octoberfest, short-term alcohol consumption
with patients with AF.16 In summary, the available
as
measured
by
a
11
1-lead
Conversely, in a
evidence does not support a clear impact of alcohol
smaller Japanese study of 517 men, moderate (>23 g
on SVT incidence or recurrence, even though it con-
alcohol/day) and heavy (>46 g alcohol/day) con-
tinues to be considered a trigger anecdotally.17
was not associated with PACs.
sumption was associated with increasing PAC frequency.12 In a case-control study of 3,966 individuals,
ATRIAL FIBRILLATION. A c u t e a l c o h o l c o n s u m p t i o n
high intake (>6 drinks/day) compared with low intake
a n d a t r i a l fi b r i l l a t i o n . The relationship between
(<1 drink/day) was associated with greater PACs. 13
alcohol acute consumption and atrial fibrillation (AF),
Whether only significant long-term or binge alcohol
particularly from heavy or binge drinking episodes,
consumption may increase PACs, or whether race,
has long been clinically recognized. Historically, most
ethnic, and/or sex-specific effects are relevant, re-
of the data has been derived from case series. 2,18
mains to be clarified in future studies.
However, contemporary studies with comparator
SUPRAVENTRICULAR
groups have similarly identified alcohol as a unique
TACHYCARDIAS. Supraven-
tricular tachycardias (SVTs) are often recurrent and
trigger for AF episodes. 16,19 Furthermore, cohort
burdensome for affected individuals who frequently
studies evaluating binge drinking, variably defined
require emergency department care. Historically, the
as multiple drinks on a single day or occasion, have
effects of alcohol on all supraventricular arrhythmias
reported significant associations with increased long-
including AF have often been considered together.
term AF risk, although this association can be difficult
However, a few studies have attempted to investigate
to disentangle from generally high consumption.20,21
links between alcohol and SVTs separate from AF. In a
Several recent studies have provided convincing
case-control study, numerically more individuals
evidence on the effects of short-term alcohol con-
with SVT were observed in those who consumed >6
sumption on discrete, near-term AF episodes. In a
drinks/day compared with <1 drink/day, but this was
population-level analysis, we used breathalyzer data
of borderline statistical significance.13 Conversely, in
to identify national events associated with alcohol
another small study, recent or long-term alcohol
consumption. 22 These events were used as instru-
consumption did not differ between SVT and control
mental variables to demonstrate that short-term
patients.14 More recently, associations of clinical risk
alcohol intake inferred by the dates of those events
factors with multiple arrhythmias were studied in the
was associated with increases in incident and recur-
UK Biobank; neither daily nor occasional (1-4 times/
rent AF emergency department visits. More recently,
week) intake of alcohol was significantly associated
we published findings from the I-STOP-AFib (Indi-
with SVT hospitalizations. 15 Data also suggest that
vidualized Studies of Triggers of Paroxysmal Atrial
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Alcohol and Arrhythmias
Fibrillation) randomized controlled trial, in which the
treatment group was allocated to n-of-1 testing of
different lifestyle triggers. 23 Among multiple evalu-
F I G U R E 2 Association of Total Alcohol Intake With Bradyarrhythmias,
Atrial Fibrillation, and Sudden Cardiac Death
ated triggers, only alcohol emerged as significant,
where short-term exposure was consistently associated with more real-time, self-reported episodes of
AF. In another prospective, case-crossover study, we
sought objectively to characterize whether real-time
alcohol consumption was acutely associated with AF
episodes.24 Individuals with paroxysmal AF were
fitted with continuous electrocardiogram monitors
and transdermal ethanol sensors. Real-time consumption of alcohol was recorded by patients using a
button on the electrocardiogram monitor, and alcohol
consumption was additionally verified using fingerprick phosphatidylethanol testing. In the 4 hours
preceding an AF episode, there was a 2-fold higher
odds of consuming an alcoholic drink and more than a
3-fold higher odds of consuming at least 2 drinks
(Figure 1). These data suggest that even 1 alcohol
drink may be sufficient to increase the risk of a
One standard drink is defined as 8 g (10 mL) of alcohol, the size of a UK standard drink. The
relationship between long-term total alcohol intake and different arrhythmias, with atrial
discrete AF episode, at least among those persons
fibrillation in red, bradyarrhythmias in blue, and sudden cardiac death in green. The shaded
with known paroxysmal AF, in contrast to the wide-
areas represent 95% CIs. Reproduced with data from Tu et al.20,70,102
spread belief that heavy or binge consumption is
required. Notably, the MunichBREW study conducted
by Brunner et al 11 at the Munich Octoberfest did not
consumption of <56 g alcohol/week (equivalent to 7
find an association of breath alcohol concentration
UK or 4 U.S. standard drinks per week) was associated
and
with the lowest AF risk (HR: 0.91; 95% CI: 0.86-0.96)
AF;
however,
the
short
electrocardiogram
recording time and the younger and healthier popu-
(Figure 2, red). Above this threshold, increasing
lation (age 34.4 years; 6.6% with heart disease) may
alcohol consumption had a positive linear association
have reduced the ability to detect an association.
with greater AF risk, whereby every additional 56 g
fibrillation.
alcohol consumed per week was associated with
Several large, observational studies have described
approximately a 5% excess risk. Similarly, in another
associations of long-term alcohol intake with incident
large prospective cohort from Sweden, 79,019 in-
AF over the years. Most studies have reported that
dividuals who had 7,245 AF events were studied.21 In
high long-term or habitual intake of any alcohol was
this report, those participants consuming more than
significantly associated with a greater risk of AF. In
180 g of alcohol per week (equivalent to 22 UK or 13
fact, we found that alcohol abuse, the most extreme
U.S. standard drinks/week) had a significantly greater
form of consumption as recognized by a health care
risk for AF. Conversely, in another recent analysis,
professional, was second only to congestive heart
other investigators pooled 107,845 individuals and
Long-term
alcohol
intake
and
atrial
failure in magnitude as a risk factor for incident AF.25
5,584 AF events from 5 different European cohorts26
However, controversy over the nature and shape of
and described an increase in AF risk associated with
this relationship continues to exist, in particular
a remarkably lower level of 14 g/week (1.75 UK or 1
related to the following questions: What defines
U.S. standard drink/week).
“high” consumption? Does a threshold exist above
Some systematic reviews and meta-analyses have
which such intake becomes significantly associated
attempted to shed insight on conflicting findings with
with greater risk? Is there a low or very low amount of
the benefit of greater statistical power. However,
alcohol that is “safe” to consume regularly? In a
somewhat differing conclusions have been reached
recent analysis, we leveraged data from the UK Bio-
even among these summary studies. In a meta-
bank prospective cohort study in an attempt to
analysis of 7 prospective studies including 12,554
characterize risk thresholds, if any, for alcohol intake
incident AF cases, a linear, dose-response relation-
with incident AF. 20 A total of 403,281 individuals,
ship was observed with an 8% (95% CI: 6%-10%) in-
21,312 with incident AF, exhibited a J-shaped rela-
crease in AF risk for every 84-g increment of alcohol
tionship
per week (equivalent to 10 UK or 6 U.S. standard
between
alcohol
and
AF,
such
that
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F I G U R E 3 Association of Individual Alcohol Beverage Consumption With Incident Atrial Fibrillation
One standard drink is defined as 8 g (10 mL) of alcohol, the size of a UK standard drink. The shaded areas represent 95% CIs. Reproduced with
permission from Tu et al.20
drinks/week).21 In another meta-analysis of 249,946
determine a causal role for alcohol in atrial arrhyth-
individuals, moderate alcohol consumption (7-14
mogenesis; such analyses are potentially less prone to
standard drinks/week) was associated with AF risk,
confounding bias and other biases than observational
whereas lower intakes were not.27 Furthermore, in
studies. However, the few studies undertaken have
this report there was a significant sex-specific inter-
also shown mixed results, with some suggesting
action, such that moderate alcohol consumption
potentially significant associations of genetically
appeared harmful in men but not women. A more
predicted alcohol use with AF 29-31 and others report-
recent meta-analysis including 10,266,315 individuals
ing no clear relationship. 32
also suggested that sex and geographic region may be
Past
in part responsible for the disparate results reported
Given that heavy long-term alcohol consumption is
by individual studies. 28 These investigators reported
clearly associated with AF risk, whether at least part
that low and moderate alcohol consumption was
of this susceptibility is reversible with alcohol cessa-
significantly associated with greater AF risk in men
tion is of clinical relevance. Several studies have re-
but not women and that such alcohol intake appeared
ported that former drinkers have an elevated risk of
harmful among European and Asian but not North
AF compared with lifetime abstainers or current
American populations.
drinkers.20,33 However, as demonstrated in our anal-
alcohol
consumption
and
atrial
fibrillation.
Mendelian randomization studies have also been
ysis of participants in the ARIC (Atherosclerosis Risk
undertaken to leverage genetic variants reliably
In Communities) study, former drinkers were more
associated with alcohol consumption in an attempt to
likely to have clinically relevant comorbidities, and
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Alcohol and Arrhythmias
F I G U R E 4 Change in Incidence of Alcohol Misuse, Alcoholic Liver Disease, Atrial Fibrillation, and Other Cardiovascular Admissions
Before and After Conversion From Dry to Wet County Status
Squares represent change in incident rates for each type of hospital admission in 7 counties that converted from dry to wet. Denominators for
incident rates were determined using 2010 U.S. census data. Incident difference is difference between incident rates before and after
referendum for a given outcome. Error bars indicate 95% CIs. Reproduced with permission from Dukes et al.37
the association of former drinkers with greater AF
analysis summarizing these data suggested that beer
was no longer statistically significant after adjusting
may be associated with a greater incident AF risk
for these potential confounders.33 Furthermore, each
compared with other beverage types, the confidence
decade of alcohol abstinence was associated with a
in this conclusion was not strong. 28 Thus, the reasons
20% lower rate of incident AF in that analysis, a
for the discrepancies in existing studies are still not
finding suggesting that earlier modification of heavy
alcohol consumption may be more beneficial for
lifetime AF prevention.
Alcoholic beverage type and atrial fibrillation. Compar-
F I G U R E 5 Time to Atrial Fibrillation Recurrence Among Those Randomized to
Abstinence and Control
atively fewer data are available on the associations of
beverage-specific alcohol with incident AF. In our
previously referenced report leveraging UK Biobank
data, we found that high intake of any alcohol
beverage appeared to be harmful. 20 However, associations of specific beverages appeared to differ at
low levels of alcohol consumption (Figure 3). For beer
or cider consumption, there was a positive linear association, with the lowest risk seen in those persons
with no consumption. In contrast, for red wine, white
wine, and spirit consumption, there were positive
curvilinear associations, with statistically significant
increased risks seen with more than low or very low
intake. Conversely, another recent study reported
similar
associations
across
different
types
of
alcohol. 26 Previous analyses have also been conflicting, with some describing wine and beer as more
harmful, 21 and others not finding any beveragespecific associations.
34,35
Although a recent meta-
Reproduced with permission from Voskoboink et al.38
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F I G U R E 6 Change in AERPs during alcohol and placebo infusions
Blue squares denote changes in atrial effective refractory period (AERP) with the alcohol infusion, and red squares denote changes with the
placebo infusion. Error bars denote 95% CIs. Reproduced with permission from Marcus et al.45.
clear and require further exploration, and they may
87.5% (from 16.8 to 2.1 standard drinks/week), and
potentially reflect differences in study size, missing
patients in the control group reduced their alcohol
data, or residual confounding. Similarly, there are
intake by 19.5% (from 16.4 to 13.2 standard drinks/
few and conflicting data on the risk of recurrent AF
week). After 6 months’ follow-up, time to AF recur-
with specific beverages, with some suggesting that
rence was greater (HR: 0.55; 95% CI: 0.36-0.84) and
beer is more likely to trigger episodes, and others
AF burden lower (0.5% vs 1.2%; P ¼ 0.01) in the
implicating wine.16,36
abstinence group compared with the control group
Modifying
alcohol
consumption
and
atrial
(Figure 5). These data confirm the long-held suspi-
fi b r i l l a t i o n . Despite the growing body of evidence
cions
supporting an association of heavy alcohol con-
contribute to AF and that a reduction from high to
sumption with a greater burden of AF, there are
lower intake in patients with established AF is of
scant direct data supporting a benefit from moder-
clinical benefit. However, ongoing uncertainty re-
ating alcohol intake, with the exception of a few
mains regarding whether modifying alcohol intake
select studies. Using ecologic methods, the existence
affects the risk of incident AF, whether complete
of “wet” and “dry” counties in Texas (where alcohol
abstinence may be of further value in those with
sales are unrestricted and restricted or prohibited,
established AF, or whether light drinking may be
that
high
alcohol
intake
does
indeed
respectively) and the conversion of counties be-
potentially acceptable (or potentially even benefi-
tween the 2 statuses were leveraged as a natural
cial, as suggested by the observational data noted
experiment to investigate whether modifying access
earlier), as desired by many patients and the general
to alcohol has measurable effects on AF.37 In sum-
public.
mary, wet counties had a greater prevalence and
Potential
mechanisms
incidence of AF, and conversion from dry to wet
fibrillation
relationship. Several
status was also associated with increased risk, find-
have evaluated the effects of alcohol on atrial elec-
ings supporting the potential public health impor-
trophysiology. These models have shown that both
tance of alcohol access (Figure 4). Although we are
short-term and long-term exposure to alcohol slows
not aware of data at an individual level on modi-
conduction velocities and reduces effective refractory
fying alcohol intake and incident AF, a landmark
periods, thus resulting in a greater vulnerability to
trial assessing effects on recurrent AF was recently
atrial arrhythmias.39,40 A few human studies have
published in patients with an established AF diag-
been historically undertaken in small numbers. 41-43
nosis.
In
longed with short-term ingestion and to a greater
who consumed 10 or more standard drinks (120 g
degree in patients with a history of alcohol-induced
alcohol) per week to either abstain from alcohol or
AF.44 Recently, we evaluated the effect of short-
38
term alcohol exposure on human atrial and pulmo-
Notably, of the 697 patients screened, three-fourths
nary vein electrophysiology. 45 In a randomized,
were excluded for lack of willingness to abstain. Of
double-blinded, placebo-controlled trial, individuals
the 140 eventually randomized, patients in the
undergoing AF ablation had intravenous alcohol
abstinence group reduced their alcohol intake by
titrated to a 0.08% blood alcohol concentration
alcohol
trial,
models
One report noted that P-wave duration was pro-
usual
controlled
alcohol-atrial
in-
their
prospective
the
preclinical
vestigators randomly allocated individuals with AF
continue
this
underlying
consumption.
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compared with a placebo infusion. In those partici-
study of AF patients wearing continuous monitors
pants assigned to the alcohol infusion, pulmonary
revealed that AF tended to occur 4 to 6 hours after
vein
alcohol consumption, thus potentially fitting with
effective
refractory
periods
significantly
decreased, whereas no significant change was noted
more vagal effects.24
in the placebo group (Figure 6). In contrast to earlier
Finally, the association of long-term alcohol con-
animal studies, no short-term change in conduction
sumption with AF could be in part mediated by other
velocities was observed. Although immediate AF
conditions along the causal pathway. For example,
inducibility was similar, these data suggest that
the development of heart failure from alcoholic car-
short-term alcohol consumption does acutely influ-
diomyopathy is a mechanism that could lead to atrial
ence atrial and pulmonary vein electrophysiology in
arrhythmogenesis. However, this may be more rele-
humans. Similarly, at least moderate long-term
vant to those persons consuming high levels of
alcohol intake has also been shown to be associated
alcohol on a long-term basis and is less likely to
with conduction slowing that may in part explain the
contribute to the propensity for AF with short-term or
propensity to AF in habitual drinkers. 46
moderate habitual intake.53 Obesity has attracted
In addition to direct effects on atrial electrophysi-
increasing attention in recent years as an influential
ologic properties, multiple investigations have re-
and modifiable risk factor for AF. 54 Alcohol intake is
ported structural and electroanatomical changes in
associated with weight gain, and indeed, alcohol
response
the
abstinence was associated with modest weight loss,
Framingham Study, we showed that long-term
as well as reduced AF burden, in a recent trial.38
alcohol intake was an independent predictor of sub-
There similarly exists a well-established link be-
sequent atrial enlargement, and an estimated 25% of
tween alcohol and hypertension, with hypertension
the
was
having the greatest population-attributable fraction
explained by left atrial enlargement.47 Furthermore,
for AF among known risk factors.55,56 Finally, alcohol
such dilatation from long-term intake may also be
significantly worsens sleep quality and obstructive
associated with worse left atrial mechanical function
sleep apnea, both of which may also predispose to
and low-voltage zones suggestive of scar.46,48-51 In
atrial arrhythmogenesis. 57,58
to
alcohol.
association
In
between
an
analysis
alcohol
and
from
AF
concordance with these findings, even short-term
S u m m a r y o f a l c o h o l a n d a t r i a l fi b r i l l a t i o n . As
consumption may depress left atrial mechanical
summarized previously, a wealth of experimental,
function, as shown in a recent cardiac magnetic
clinical, and population evidence supports an asso-
resonance study in binge drinkers.52
ciation of alcohol with incident and recurrent AF.
It is also possible that alcohol may predispose to
However, there are continuing areas of uncertainty.
episodes of AF through autonomic system changes.
From a clinical and population perspective, a crucial
Alcohol has been shown to be acutely associated with
question that remains is whether any alcohol is
an increase in sympathetic activity and a decrease in
harmful for incident AF, recurrent AF, or both. One
vagal tone, as manifested clinically by increases in
interpretation of the totality of data is that, in
heart rate and reductions in heart rate variability.11,52
contrast to other cardiovascular diseases, there either
In related fashion, individuals with alcohol-induced
is no clear “safe” amount of alcohol to consume that
AF often similarly report vagal tone as an initiating
does not increase the risk of AF, or, if such a threshold
trigger, a finding perhaps supporting an arrhythmo-
exists, it has yet to be adequately and consistently
genic role for enhanced vagal tone following short-
defined.59 This is an appropriately cautious conclu-
term alcohol consumption.16 Indeed, data published
sion, particularly for those persons who may already
in a recent study in binge drinkers support this
be at elevated risk of AF development. It could be
“rebound” predominance of parasympathetic activity
argued that the onus now exists for an absence of
and vagal tone 24 to 48 hours following short-term
harm to be proven given consistent associations of
alcohol intake, as reflected by slower heart rates and
moderate and even low alcohol intake with AF, at
variability.52
para-
least among certain subgroups. However, because of
sympathetic response could thus in part explain the
the near certainty that regular alcohol consumption
propensity for AF to occur following, but not neces-
will persist in our society, proving or disproving such
sarily during, a short-term episode of drinking.
harm continues to be of great clinical and public
greater
heart
rate
Such
a
Interestingly, whereas our randomized trial of intra-
health significance. Further adequately powered
venous alcohol in those patients undergoing AF
studies with individuals habitually consuming low
ablation failed to reveal an immediately heightened
and very low amounts of alcohol are thus required in
propensity to AF, 45 our case-crossover ambulatory
this regard.
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ATRIAL FLUTTER. Atrial flutter (AFL) often coexists
previous myocardial infarction,67 as well as in pa-
with AF, and as a result, many studies have amal-
tients admitted to an acute alcohol detoxification
gamated both for analyses. That said, there are
center.68 In contrast, the MunichBREW study did not
several studies reporting data on alcohol and AFL
observe any relationship between the level of short-
separately. In a historical case-control study, the
term intoxication and the frequency of PVCs.11 If a
trend was toward more cases of AFL in patients who
true causal relationship between short-term alcohol
exhibited high (>6 drinks/day) compared with low
consumption and PVCs does exist, it may be mild and
(<1 drink/day) alcohol intake.13 We previously found
affect those persons at higher cardiovascular risk, and
that younger individuals with AFL were reported to
this remains of uncertain clinical significance.
be significantly more likely to drink alcohol daily
compared with control subjects, and there was a
linear association between increasing alcohol intake
and a greater odds of having AFL.60 In this analysis,
right atrial effective refractory periods were also
found to be lower in those with greater alcohol
intake; this may be a possible mechanism predisposing alcohol drinkers to AFL. However, in another
smaller report, patients with AFL did not have
significantly different short- or long-term alcohol
consumption patterns compared with control subjects.14 In totality, however, given the close clinical
and mechanistic interrelationships of AF and AFL and
the abundance of recent data supporting a link between alcohol and AF discussed earlier, it seems
plausible to posit that an association may also exist
between alcohol and AFL, even though the evidence
base is more limited. 61
ventricular tachycardia (VT) and ventricular fibrillation (VF),69 although recent data have shed some
light on the distinct associations of alcohol with
ventricular arrhythmias and SCD. In an analysis of
more than 400,000 participants involved in the UK
Biobank study, we observed a clear U-shaped relationship for long-term alcohol consumption and the
risk of SCD (Figure 2, green), although no significant
association was seen in the group of patients who
were hospitalized with or died of VT or VF.70 Notably,
a similar number of events was captured for both
outcomes in this study over a follow-up period of
more than a decade. Other studies have been conducted only in select patient populations. Although
strated an increased risk of VF in those consuming
CONTRACTIONS.
alcohol consumption and premature ventricular contractions (PVCs) is uncertain, and the evidence is
conflicting.
and malignant ventricular arrhythmias, including
segment elevation myocardial infarction demon-
Whether any association exists between long-term
62-65
studies have
tion,71,72 a case-control study of patients with ST-
TACHYARRHYTHMIAS
VENTRICULAR
ARRHYTHMIAS. Few
some studies have also demonstrated no associa-
ALCOHOL AND VENTRICULAR
PREMATURE
VENTRICULAR
explicitly examined the relationship between alcohol
One small study of 443 men found
that those without cardiovascular disease who con-
more than 96 g alcohol per week.73 Interestingly, in
patients with a diagnosis of alcoholic cardiomyopathy, abstinence from alcohol may be associated with
fewer arrhythmic events, defined in this study as
either sudden death or an episode of sustained VT or
VF.74
sumed significant amounts of alcohol (250 g/week)
SUDDEN CARDIAC DEATH. Ecologic studies have
appeared to have a greater risk for PVCs, but this was
demonstrated variation in the frequency of SCDs,
not the case in patients with cardiovascular disease.63
which have been observed to occur more frequently
In contrast, a small Japanese study recently reported
following days on which binge drinking is most
an association of “light” (<161 g/week) drinking with
common. The rates of SCD occurring in Lithuania and
fewer PVCs, but this relationship was not seen at
Russia in the 1990s were highest on Saturday, Sun-
higher levels of alcohol consumption. We found no
day, and Monday, elevated in tandem with the
relationship between alcohol and PVCs in the CHS
increased rates of deaths from accidents, violence,
(Cardiovascular Health Study), and another group
and alcohol poisoning seen on these days.75,76 In one
similarly failed to identify an association using
of the earliest epidemiologic studies on the topic,
data from ARIC.64,65 Whether any true relationship
rates of sudden death were noted to be higher in
exists thus requires confirmation in future studies.
workers who had previously been reprimanded by
Potentially more convincing is the possibility for
their workplace for working while intoxicated. 77 Later
short-term alcohol consumption to be associated with
data suggested the potential for a U-shape relation-
an increased frequency of PVCs, as seen in largely
ship between long-term alcohol consumption and
older studies of patients with relevant comorbidities
SCD, such that regular consumption of low to mod-
such as chronic obstructive pulmonary disease66 and
erate amounts of alcohol may actually confer some
Wong et al
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FEBRUARY 2023:266–279
Alcohol and Arrhythmias
protection against SCD. In case-control studies from
interval prolongation has been documented in those
the 1980s, nondrinkers appeared to experience a
patients hospitalized for acute alcohol intoxication, 88
or at
in long-term heavy alcohol consumers, 2 and in pa-
least when compared with those consuming up to 3
tients with alcoholic liver cirrhosis, 89 although this
higher risk of SCD compared with drinkers,
drinks/day.
78
79
finding has not been consistently shown with short-
Much of our current understanding of the relation-
term alcohol consumption in healthy subjects.90,91
ship between alcohol and SCD has come from analyses
QRS duration prolongation has also been docu-
of large, prospective cohort studies performed in the
mented with short-term alcohol consumption in
last 2 decades. Virtually all contemporary cohort
humans, 92 as well as with long-term alcohol con-
studies have identified long-term consumption of
sumption in dogs. 93 In the latter study of 11 dogs fed
approximately 1 drink/day to be associated with the
alcohol for at least a year, dilation and localized
lowest risk of SCD,70,80-83 and an excess in SCD risk is
swelling of the nonspecialized region of intercalated
generally seen in those consuming more than 3 to 4
disks were observed in the ventricular muscle and
drinks/day.70,82-84 However, the magnitude of risk
Purkinje fibers.93 The QT variability index, a marker
reduction seen with consumption of 1 drink per day
of repolarization lability calculated as the ratio be-
varies substantially among studies, ranging from a
tween the QT interval and heart rate variability,
20%,70 to 80%, 80 compared with reference groups that
which has been associated with an increased risk of
consist of those persons consuming very small
VT and VF,94 may also be increased in patients un-
amounts of alcohol or none at all. Regarding types of
dergoing acute alcohol withdrawal.95
alcoholic beverages, whereas some data suggest a
Whether the greatest risk of ventricular arrhyth-
more evident protective association with wine con-
mias occurs with acute intoxication, in the with-
sumption over beer and spirits,70 other studies have
drawal period, or with the long-term cumulative
failed to replicate the same findings.81,83
consumption of alcohol remains unclear. In silico
Although SCD has traditionally been assumed to
analyses by Sutanto et al 96 demonstrated concen-
represent a proxy for fatal ventricular arrhythmias,
tration- and tissue-dependent effects of ethanol. In
this notion has been challenged in recent times. Older
their ventricular cardiomyocyte models, high con-
studies suggested that malignant arrhythmias in the
centrations of ethanol slowed ventricular conduc-
setting of coronary artery disease underlie 70% to
tion velocity and promoted both the inducibility
80% of sudden deaths,85,86 but it is now recognized
and stability of re-entrant arrhythmias, 96 although
that the etiology of sudden death is more heteroge-
no effect of low ethanol concentrations were seen
nous.87 This is at least in part the result of improve-
on the ventricular action potential duration.96 In
ments in coronary artery disease mortality. 85,86 Many
electrophysiology studies of 14 patients with cardiac
of the aforementioned studies also defined SCD
disease, acute intoxication following ingestion of
broadly as death occurring within 1 hour of symptom
28 g alcohol resulted in shortening of the effective
onset,77,81,82,84 likely capturing many noncardiac
refractory period of the ventricular myocardium,
deaths, although some studies additionally specified
thus providing further evidence for a mechanism
the
hemodynamic
promoting re-entry in acute intoxication. 43 Con-
compromise before death, to increase the specificity
trasting with the foregoing, in a study of adult rats
for an arrhythmic origin.80,83 In 1 postmortem study
exposed to an alcohol solution for 7 weeks and
capturing nearly all out-of-hospital sudden deaths in
exposed to a single injection of isoproterenol, it was
San Francisco County (California, USA) between 2011
the “alcohol withdrawal group” (having had cessa-
and 2014, only 56% of deaths were confirmed as a
tion of the alcohol solution the night before injec-
sudden arrhythmic death, whereas 40% of deaths
tion) that experienced the highest incidence of VT,
were considered noncardiac. 87
VF, and sudden death, rather than those continu-
absence
of
any
preceding
ously exposed to alcohol or control subjects given
POTENTIAL MECHANISMS. In light of conflicting
only tap water.97 One canine study has even
observational evidence, mechanistic and experi-
demonstrated a protective effect of acute ethanol
mental studies provide a number of explanations for
exposure by reducing the incidence of VF elicited
alcohol’s contributions to ventricular arrhythmo-
by rapid ventricular pacing during acute occlusion
genesis, although none of these data are as consistent
of
or as rigorously conducted as for AF.
receiving an ethanol infusion. 98
the
left
anterior
descending
artery
while
The clearest evidence is available from the effects
Electrolyte abnormalities, in particular hypomag-
of alcohol on the electrocardiogram, where delete-
nesemia and hypokalemia, may arise with long-term
rious changes to ventricular conduction are seen. QT
intake of alcohol, secondary to poor oral intake of
275
276
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Alcohol and Arrhythmias
these
urinary
likely to be harmful (or potentially most protective) ,
loses.99 These deficiencies are also exacerbated in the
electrolytes,
gastrointestinal
and
but otherwise no clear evidence of relationships with
withdrawal phase, with autonomic hyperactivity and
specific beverage types was observed. Similarly, a
increased pH resulting from respiratory alkalosis.99
report from the ARIC and CHS studies did not find any
Long-term alcohol consumption also has a toxic ef-
increase
fect on myocardium, by promoting oxidative stress,
increasing alcohol intake.103 Thus, the limited but
in
sinus
node
dysfunction
risk
with
impairing mitochondrial bioenergetics, and structural
overall data to date suggest that there is no definitive
remodeling, which culminates in a dilated cardio-
increase in risk of sinus node dysfunction with
myopathy. 53 It is thought that alcohol-induced car-
alcohol consumption.
diomyopathy is seen only at the heaviest levels of
CONDUCTION DISEASE. Comparatively more, but
alcohol consumption, with consumption of at least
still limited, data are available regarding the possible
90 g per day for at least 5 years as a rough estima-
effects of alcohol on conduction properties or abnor-
tion.53 The risk of ventricular arrhythmias in these
malities (eg, bundle branch or fascicular blocks).
patients appears similar to other forms of dilated
Several small case series in individuals following
cardiomyopathy.100,101
acute alcohol intake described P-wave, PR interval,
SUMMARY OF VENTRICULAR ARRHYTHMIAS AND
SUDDEN CARDIAC DEATH. It is challenging to iden-
tify specific and unifying explanations underlying the
apparent protective associations of low to moderate
long-term alcohol consumption with SCD given an
absence of clear and universal mechanisms for SCD
and a paucity of epidemiologic evidence specifically
examining ventricular arrhythmias. In light of mechanistic and experimental studies that point toward
more deleterious effect of alcohol on ventricular
arrhythmogenesis, it is possible that this relationship
is partially confounded by associations observed for
other clinical outcomes, including a protective association of alcohol consumption across the spectrum of
intake with coronary artery disease 7 and no significant
association of all-cause mortality with low to moderate
intake.7 Moreover, whether it is acute intoxication,
withdrawal, long-term consumption, or a combination
of the 3 that poses the greatest risk for ventricular arrhythmias remains to be clarified, which would provide further clinical and mechanistic insights.
and QRS interval prolongation.88,90,92 Conversely, 1
small invasive study in 14 patients found shorter
intra-atrial conduction times and refractory periods
of both the atrioventricular node and the ventricular
myocardium after short-term alcohol consumption.43
In contrast, the much larger MunichBREW study
revealed only an elevated heart rate as blood alcohol
content rose, but no changes in PR intervals or QRS
durations.91 As with other arrhythmias, it is possible
that long-term alcohol intake may have differing effects compared with acute or binge consumption. In
an animal model, long-term alcohol intake was associated
with
longer
HV
and
QRS
intervals.93
Conversely, in a separate analysis of the UK Biobank
study performed by Khurshid et al15, occasional and
frequent alcohol intake was associated with 14% and
10% lower risks, respectively, of conduction system
diseases
compared
with
infrequent
intake.
In
contrast, in our analysis of the UK Biobank data, we
did not demonstrate long-term alcohol intake to be
associated with a heightened risk of atrioventricular
block.102 Similarly, in a Finnish cohort, we failed to
find any association between long-term alcohol con-
ALCOHOL, CONDUCTION DISEASE, AND
sumption and second- or third-degree atrioventric-
BRADYARRHYTHMIAS
ular block.104
SINUS NODE DYSFUNCTION. In an analysis of the UK
consumption of alcohol was not associated with an
Biobank prospective cohort study, we demonstrated
increased risk of pacemaker implantation; in fact,
that increasing total alcohol intake was not associated
point estimates were in the opposite direction,
with a greater risk of sinus node dysfunction
consistent with lower risk although confidence in-
(Figure 2, blue).102 In fact, point estimates were sug-
tervals crossed unity. 102 Apart from a comparable
gestive of a potentially protective influence across the
report leveraging data from the same cohort,15 we are
spectrum of alcohol consumption, with significant
not aware of other large, population-based studies
associations of alcohol consumption between 10 and
evaluating the association of alcohol intake patterns
65 UK standard drinks per week and a lower risk of
with pacemaker implantations.
In our analysis of the UK Biobank data, increasing
sinus node dysfunction observed. Exploratory ana-
Thus, although the data are somewhat conflicting,
lyses raised the possibility of white wine being least
most studies have failed to identify a clear or
Wong et al
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Alcohol and Arrhythmias
consistent influence of acute alcohol intake on con-
CONCLUSIONS
duction system disease.
The relationship between alcohol and arrhythmias
IMPLICATIONS FOR CLINICAL PRACTICE,
PUBLIC HEALTH, AND FUTURE RESEARCH
As summarized previously, the totality of data suggest that alcohol intake is associated with either a
harmful effect or a neutral effect on the risk of
arrhythmia. Although some results raise the possibility of benefit with low or very low consumption,
this is noticeably less pronounced than what is
observed for other cardiovascular conditions, for
example,
ischemic
heart
disease.
Furthermore,
observational studies are subject to biases that may in
part be responsible for the apparent beneficial or even
neutral associations described. Given the significant
personal and societal harm conferred by excess
alcohol intake, it is clear that no more than low consumption should be advised for the general public
and
certainly
in
those
persons
already
with
arrhythmia or at high risk of arrhythmia development. Notably, currently available U.S. guidelines, all
relying on observational data thus far, recommend a
continues to be an active area of investigation. Current data suggest that heavy alcohol consumption is
associated with an increase in AF and SCD risk.
Conversely, there are either conflicting or insufficient
data to suggest a definite harm of alcohol on other
arrhythmias, such as PACs or PVCs, VT or VF, and
bradyarrhythmias.
Given
the
other
known
deleterious
effects
of
excessive
alcohol
health
consumption, moderation of intake is prudent for
those patients with established arrhythmia or at high
risk of arrhythmia. However, further research is
required to clarify arrhythmogenic mechanisms, to
determine the safest levels of consumption, and both
specific alcohol and individual-level characteristics
that could influence the relative risk of various
arrhythmias.
FUNDING SUPPORT AND AUTHOR DISCLOSURES
Dr Wong has received support from a Mid-Career Fellowship from the
Hospital Research Foundation and a Postdoctoral Fellowship from
maximum consumption of 2 drinks per day for men
the National Heart Foundation of Australia; and has reported that the
and 1 drink per day for women.105 Although it has
University of Adelaide has received on his behalf lecture, travel,
often been suggested that undertaking randomized
and/or research funding from Abbott Medical, Bayer, Boehringer
controlled trials on alcohol consumption, the gold
Ingelheim, Medtronic, Novartis, Servier, St Jude Medical, and Vifor
Pharma. Dr Tu has received support from a Postgraduate Scholarship
standard for establishing causation, may be imprac-
from the National Health and Medical Research Council of Australia.
tical or even ethically problematic, we would argue
Dr Marcus has received support from the National Institute on
that the pursuit of these trials is worthwhile given the
widespread benefits that the resulting knowledge
would confer because of the ubiquitous presence of
Alcohol Abuse and Alcoholism of the National Institutes of Health
(grant R01AA022222); has received research funding from Baylis
Medical; has served as a consultant for Johnson & Johnson and
InCarda; and has holding equity in InCarda.
alcohol in our society. Indeed, the field of cardiac
electrophysiology has led the way, producing the
ADDRESS FOR CORRESPONDENCE: Dr Gregory M.
only true interventional and randomized trials of
Marcus,
alcohol in cardiovascular medicine and providing
California-San Francisco, 505 Parnassus Avenue,
novel and directly pertinent information useful to the
M1180B, San Francisco, California 94143, USA. E-mail:
public and clinicians alike.
[email protected]. Twitter: @gregorymarcus.
Division
of
Cardiology,
University
of
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