- Academic Editors
Background: Alcohol is a pervasive substance in the US and the world in general. Cardiac arrythmias, specifically atrial fibrillation, are also a critical health issue. The interplay between alcohol and arrythmia is explored here. Methods: Original research, editorials and other literature reviews were searched and assessed for candidacy for inclusion and ability to contribute to this article. Conclusions: Alcohol consumption has a significant interplay with cardiac arrhythmia.
Alcohol consumption is a regular phenomenon among most regions and cultures of the world, although patterns vary. It has been evident that the first alcohol preparation was 8000 BC when humans started building sedentary communities. The earliest proof was through chemical analysis of pottery jars found in Jiahu, North China [1]. In 2016, World Health Organization (WHO) estimated that more than 2.3 billion people worldwide were current drinkers [2]. 83.1% of US citizens are current or former regular consumers of alcohol, whereas in Europe this numbers stands at 76.6% and within the African continent is only 42.6%. Interestingly, those that due consume alcohol on a regular basis take in on average 33–37 g/day. Women tend to abstain from alcohol more and have a lower incidence of binge drinking [3]. Alcohol consumption trends show that related disorders are likely to rise as per capita consumption has increased 2.9% from 2019–2020, with this trend set to continue [4]. More than 3 million people died due to harmful alcohol consumption with almost 19% of all deaths attributable to alcohol consumption worldwide were due to cardiovascular diseases.
In the US, alcohol consumption varies among the subpopulation groups. Moreover, health consequences differ among racial and ethnic groups. While the highest prevalence was reported among white respondents, native Americans and blacks were more affected by alcohol-related health consequences [2].
Although low to moderate alcohol consumption has been associated with lower rates of all-cause mortality, nonfatal acute myocardial infarction and coronary death, multiple studies demonstrate that the relation between alcohol intake and all-cause and cardiovascular mortality has a J-shaped or U-shaped pattern [5].
Alcohol consumption is associated with many side effects in different systems
including the cardiovascular system. High levels of alcohol intake found to be
associated with an increased risk of hypertension and overall incident
hypertension. Compared with no alcohol intake, consumption of
Although not fully understood, alcohol has also arrhythmogenic effects through multiple mechanisms including electrophysiological, chemical, and autonomic disturbances. This is explaining the data that shows an increased risk of atrial and ventricular as well as sudden cardiac death.
In this review, we will discuss the literature studying the relationship between alcohol and cardiac arrhythmia including causality, types and the level of alcohol intake and the underlying possible pathophysiological mechanisms.
Research and construction of the review article was performed as follows. Literature search on scholarly research search engines were performed utilizing Pubmed, Ovid, Google Scholar. Primary research was prioritized. Keywords such as “Atrial Fibrillation”, “Alcohol”, “Arrythmia”, “Sudden Cardiac Death”, among others were used. This information was reviewed by both authors and both authors contributed significantly to this article.
Sudden cardiac death is a very dramatic and serious event in a patient’s life.
Thankfully statistics in treatment of sudden cardiac death (SCD) are improving,
with more patients surviving to hospital discharge on a yearly basis. Victims and
survivors of SCD are a heterogenous group of patient, with many factors
contributing to their initial event and total survival [7]. As alcohol
consumption is such a common social phenomena, investigation into its role in SCD
risk has been examined, with ultimately complex findings. In one study among
22,071 male physicians, a total of 141 sudden cardiac deaths were documented over
the 12 year monitoring period. Those who consume
Although many studies were done between alcohol consumption and Atrial
fibrillation association, less studies applied on the effect of other atrial
arrhythmia. Ettinger et al. [13] as one of the first who studies the
effect of excessive alcohol intake and cardiac arrythmia. Among 24 patients with
recent alcohol ingestion, atrial fibrillation in addition to atrial flutter,
atrial tachycardia, junctional tachycardia, multiple premature atrial
contractions, multiple premature ventricular contractions (PVCs) and ventricular
tachycardia were observed [13]. Kupari et al. [14] studied 289 patients
aged
In MunichBREW study, they prospectively enrolled 3028 voluntary participants in
whom smartphone based electrocardiograms (EKGs) were analyzed for cardiac
arrhythmia (including sinus tachycardia, sinus arrhythmia, premature
atrial/ventricular complexes, atrial fibrillation/flutter) associated with breath
alcohol concentration (BAC) measurements. In this study mean age of participants
was 34.4
Although many studies illustrate the positive association of alcohol consumption and atrial fibrillation, few studies found protective effects of alcohol. Psaty et al. [16] studied the independent risk facors of new onset atrial fibrillation among old adults. They found that high level of alcohol consumption was associated with decrease risk of atrial fibrillation among all patients with or without clinical vascular disease [16]. It is not clear how this factors in to the rest of the literature that establishes a negative effect of alcohol on atrial fibrillation as well as general cardiovascular risk.
Atrial fibrillation is absolutely no stranger to any healthcare practitioner in
the US or worldwide. In 2017, 37.5 million people carried the diagnosis of atrial
fibrillation with 3.5 million new cases that year, with these numbers expected to
increase over time [17]. This is a serious public health issue as atrial
fibrillation contributes to multiple consequences such as stroke, affecting 2.5
million Americans per year [18]. The World Health Organization estimates that 6%
of global deaths are related to alcohol use, and alcohol related cardiovascular
disease is related to 12% mortality [19]. Alcohol consumption is also a
worldwide issue that contributes significant to various diseases [20]. Acute
alcohol intoxication has classically been associated with so called “Holiday
Heart”, with atrial fibrillation developing within 12–36 hours of binge alcohol
intoxication [21]. Chronic alcohol consumption is associated with the development
of various arrythmias including atrial fibrillation, sinus tachycardia and PVCs
[22], with 33% of patients with atrial fibrillation being considered alcoholics.
High alcohol consumption is directly associated with an increase in atrial
fibrillation, with more moderate consumption being controversial at times [23].
The populations of the ONTARGET and TRANSCEND trials were evaluated for their
alcohol consumption. They found that moderate alcohol consumption, 1–14
drinks/week in women and 1–21 drinks/week in men, increased the risk of atrial
fibrillation with a hazard ratio of 1.16 compared to low intake, which was
To counter a majority of the data available, there are some indicators of
alcohol being protective of atrial fibrillation. UK BioBank participants aged
from 49–69 years old showed a J-shaped curve in regard to alcohol consumption.
Individuals consuming 1–7 drinks per week actually had less atrial fibrillation
than those who had
Alcohol’s direct relationship with atrial fibrillation is fairly clear but
tangential effects are also just as important. As has been well established,
atrial fibrillation is associated with a risk of stroke. To mitigate this risk,
therapeutic anticoagulation is prescribed to appropriate patients [20]. Reddiess
et al. [34] found that alcohol consumption did not enhance stroke risk
in those with atrial fibrillation. The obvious question therefore is what is the
interplay between alcohol and risk of anticoagulation. The databases for the Swiss-AF and Ground-Breaking
Electroporation-based intervention for Atrial Fibrillation Treatment (BEAT-AF)
were assessed for bleeding events as a secondary outcome. They
found that non-drinkers, classified as 0 to
While certainly alcohol has an effect on arrythmia, the question remains is it a primary driver of arrythmia or does it predispose to a phenomenon that is already to occur. Shared risk factors such as hypertension and obesity are associated with development of atrial fibrillation as well as being related to increased alcohol consumption [37]. Hypertension is clearly seen in chronic consumers of alcohol, with a statistically linkage starting with 3 drinks a day. There is clearly cross over between previously mentioned mechanisms, such as renin-angiotensin-aldosterone stimulation, vasoreactivity due to intracellular calcium increase and inflammation and oxidative injury. Autonomic activation has been found to be integral in rats, with alcohol stimulating the adrenal glands to increase heart rate, cardiac output and systolic blood pressure [38]. Hypertension, even mild hypertension has been associated with significantly increased left atrial size [39]. This increase in size is associated with decreased chance that sinus rhythm will be able to be maintained and is a strong predictor of development of nonvalvular atrial fibrillation [40]. Similarly obstructive sleep apnea (OSA), especially if left untreated, can lead to increased atrial fibrillation risk and burden. This obstructive sleep apnea promotes arrhythmogenesis through oxidative stress and excess sympathetic activity. Meta-analyses have shown that alcohol consumption increases the risk of OSA by up to 25% [41].
The basis for alcohol induced arrhythmogenesis is primarily based on its effects
in the myocardium. In silico models of both ventricular and atrial tissue,
alcohol has been shown to alter ion channel function and myocytes currents.
Alcohol reduces sodium, calcium and transient-inward potassium channel function.
Alcohol also enhances I
In atria tissue models, low dose ethanol increased reentry duration and shifted vulnerable window to a shorter stimulated S1S2 interval, leading to a higher vulnerability for stable arrythmia. Higher doses, 10-fold atria dose, was needed to cause this same effect on the ventricle. This effect of increased stable reentry was also seen in long-standing atrial fibrillation models although atrial fibrillation rotors were seen to be more meandering with higher alcohol concentrations, likely promoting further propagation of atrial fibrillation. Heart failure models have also shown similar increased stable reentry with increasing alcohol concentrations [42]. Heart failure also shows altered intercellular coupling, predominantly at higher doses. This is accomplished by prolonged reentry vulnerable periods [42]. Conversely, low dose alcohol led to reduced reentry through Ik1 channel inhibition, though in atrial fibrillation this effect is ameliorated due to atrial fibrillation effect on Ik1 channel. Inflammation is well known to be associated with atrial fibrillation instigation. Transient T2-signal intensity seen 1 day after binge drinking suggests myocardial edema, hyperemia and inflammation with excess alcohol consumption. This inflammation leads to Interluekin-6 down-regulation and therefore conduction slowing through gap junction protein connexins 43 and 40. These gap junction proteins are found predominantly in the atria, linking inflammation to atrial arrhythmias [21].
All the above, as well as other mechanisms, lead to autonomic dysfunction as a complication of alcohol consumption. Increased sinus tachycardia often occurs with acute intoxication. Vagal tone also plays a key role in arrhythmogenesis. In a study of 15 healthy volunteers which were given ethanol infusion. Markers of vagal activity such as periodic repolarization dynamics as well as deceleration capacity were assessed during infusion achieving maximum blood alcohol concentration of 0.5 mg/L, intoxicating doses. Periodic repolarization dynamics was increased and deceleration capacity was decreased showing reduced parasympathetic activity/vagal activity [44].
Another mechanism of arrythmia in atrial fibrillation is fibrosis and scar. Increasing fibrosis is potentially protective in forming reentry in the atrial although interestingly increased the duration and stability of reentrant arrythmias in the ventricular. After myocardial infarction, remodeling of border zone ion channels occurs. Mild to moderate fibrosis is not affected by alcohol but the presence of alcohol reduced reentrant arrythmias in extensive fibrosis [42]. Another mechanism of alcohol pathology is oxidative stress. Increased Nicotinamide adenine dinucleotide+Hydrogen/Nicotinamide adenine dinucleotide (NADH/NAD+) ratio with accumulation of acetaldehyde is a consequence of ethanol metabolism. This decreases intra-cellular antioxidant enzymes levels/activity. This lack of antioxidant protection will lead to myocyte disarray, apoptosis and contractile protein fragmentation. These changes are seen within 2–18 weeks of alcohol consumption. Reactive Oxygen Species (ROS) scavenger administration prevented alcohol-related scarring, apoptosis and cardiac structure alternations [6]. Further evidence of ROS-species linking atrial fibrillation and alcohol was shown through investigation done through Lung-AN Hsu et al. [45]. They generated mitochondrial aldehyde dehydrogenase 2 (ALDH2) to assess the effect on alcohol and AF with and without protection from reactive-oxygen species. Test and control mice both showed similar inducibility of AF without alcohol administration. With ethanol administration, ALDH2 knockout mice showed higher 4-hydrozy-ytrans-2-nonenal (4-HNE) levels and greater AF inducibility. These aldehydes being present are also fibrogenic, through the TGF-beta 1 pathway, which was confirmed by ALDH2 knock out mice showing more severe fibrosis after ethanol consumption compared to control [45]. Alcohol intake caused increased angiotensin II and norepinephrine levels [6]. Angiotensin II activates angiotensin II type 1 receptor which stimulates fibroblast proliferation and apoptosis and cardiomyocytes, which contributes to fibrosis of the atria. Therapeutics such as Angiotensin-Converting Enzyme-inhibitors have been shown to prevent this fibrosis of the atrial and reduce associated atrial fibrillation [43].
While atrial fibrillation is a complex topic, with many contributory factors, alcohol consumption remains an important modifiable risk factor in the US as well as worldwide. Through direct electrophysiologic effects as well as worsening other risk factors for atrial fibrillation, alcohol has a direct and largely negative effect on atrial fibrillation. An important gap in knowledge and study is research of alcohol nd arrythmias other than atrial fibrillation. This is an important topic that would be a crucial direction of study going forward. Overall, their seems to be a significant arrythmogenic risk when it comes to almost any alcohol consumption, although “binge” drinking is a definite risk. Interestingly, level of alcohol consumption noted in this review that can lead to pathology and overt arrythmias actually fall within the acceptable range of alcohol consumption by United States Preventative Task Force guidelines. By 2018 publication, unhealthy alcohol consumption is defined as more than 4 drinks per day for men under 65 years old and more than 3 drinks for women of any age and men over 65 years old [46]. As mentioned above, even alcohol consumption under this limit can cause arrythmia. This can be understandably confusing to clinicians, not to mention patients that are trying to live a “healthy” life. The above information is further support for clinicians counseling patients on healthy lifestyle habits, although discussion of appropriate alcohol consumption takes into account not just the arrhythmogenic risks, but all potential effects.
Both authors, JK and AA contributed equally and significantly to the research and writing of this manuscript. Each Author was given divided sections of the manuscript to author and the other author than proofread the passages.
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This research received no external funding.
The authors declare no conflict of interest.
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