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Canadian Journal of Cardiology

Mechanisms and Therapeutic Opportunities in Atrial Fibrillation in Relationship to Alcohol Use and Abuse

  • Author Footnotes
    ∗ These authors contributed equally to this work.
    Benedikt Linz
    Footnotes
    ∗ These authors contributed equally to this work.
    Affiliations
    Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Author Footnotes
    ∗ These authors contributed equally to this work.
    Julie Norup Hertel
    Footnotes
    ∗ These authors contributed equally to this work.
    Affiliations
    Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Thomas Jespersen
    Affiliations
    Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • Dominik Linz
    Correspondence
    Corresponding author: Dr Dominik Linz, Maastricht UMC+, Maastricht Heart+Vascular Center, 6202 AZ Maastricht. Tel.: +31(0)43-3875093.
    Affiliations
    Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

    Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia

    Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands
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  • Author Footnotes
    ∗ These authors contributed equally to this work.
Open AccessPublished:April 15, 2022DOI:https://doi.org/10.1016/j.cjca.2022.04.009

      Abstract

      Excessive drinking has detrimental effects on the cardiovascular system. Atrial fibrillation (AF) after alcohol binge drinking, also named “holiday heart syndrome,” is well established. However, chronic lower levels of alcohol intake also may increase AF risk. In this review, we aim to provide a comprehensive overview of the epidemiology and pathophysiology by which alcohol may be responsible for AF and discuss whether alcohol abstinence is required for optimal rhythm control as well as to maintain sinus rhythm in patients with AF. The pathophysiologic mechanisms responsible for the relationship between alcohol consumption and AF may include both direct and chronic effects increasing AF burden. Acute effects may include arrhythmogenic changes (such as shortening in atrial refractoriness, slowing in conduction velocity, and increased atrial ectopy) and an autonomic imbalance. Chronic changes contributing to the development of an arrhythmogenic substrate involve atrial structural and functional remodelling processes due to atrial dilation, elevated pressures, and fibrosis formation. In addition, alcohol consumption contributes to developing concomitant AF risk factors such as obesity, sleep-disordered breathing, and hypertension. Alcohol abstinence is associated with a reduction in AF recurrence and overall burden and moreover improves AF risk factor development such as obesity, hypertension, sleep apnea, and AF-related consequences such as stroke. In conclusion, alcohol consumption is associated with atrial arrhythmia and a wide range of cardiovascular comorbidities. Although further evidence is needed, current knowledge indicates that there might not be a safe level of alcohol consumption that does not increase AF risk.

      Résumé

      L'excès d'alcool a des effets néfastes sur le système cardiovasculaire. Une fibrillation auriculaire (FA) succédant à une consommation excessive d'alcool, également appelée "syndrome du cœur en vacances", est un phénomène bien établi. Cependant, une consommation chronique d'alcool à des niveaux plus faibles peut également augmenter le risque de FA. Dans cette revue de littérature, nous visons à fournir un aperçu complet de l'épidémiologie et de la pathophysiologie par lesquelles l'alcool peut être responsable de la FA et à discuter si une abstinence d'alcool s'avère nécessaire pour un contrôle optimal du rythme ainsi que pour maintenir un rythme sinusal chez les patients souffrant de FA. Les mécanismes pathophysiologiques responsables de la relation entre consommation d'alcool et FA peuvent inclure des effets directs et chroniques, augmentant le fardeau que constitue la FA. Les effets aigus peuvent inclure des perturbations arythmogènes (telles que le raccourcissement de la période réfractaire au niveau auriculaire, un ralentissement de la vitesse de conduction, et une augmentation d'évènements auriculaires ectopiques) et un déséquilibre du système nerveux autonome. Les changements chroniques contribuant au développement d'un substrat arythmogène impliquent des processus de remodelages structurel et fonctionnel de l'oreillette dus à la dilatation de l'oreillette, aux pressions élevées, et à la formation de fibrose. En outre, la consommation d'alcool contribue à l'apparition de facteurs de risque de FA concomitants tels que l'obésité, les troubles respiratoires du sommeil et l'hypertension. L'abstinence d'alcool est associée à une réduction de la récurrence de la FA et du fardeau qu'elle représente globalement, et elle améliore de surcroît la régulation de facteurs de risque de FA tels que l'obésité, l'hypertension, l'apnée du sommeil et des conséquences liées à la FA telles que l'accident vasculaire cérébral. En conclusion, la consommation d'alcool est associée à l'occurence d'arythmies auriculaires et à un large éventail de comorbidités cardiovasculaires. Bien que des preuves supplémentaires soient nécessaires, les connaissances actuelles indiquent qu'il n'existe peut-être pas de niveau de consommation d'alcool sans danger qui n'augmente pas le risque de FA.
      Many people drink alcohol to relax and socialize, and alcohol consumption is an accepted and popular part of Western culture. According to the Global Status Report on Alcohol from the World Health Organisation (WHO),
      World Health Organization
      Global status report on alcohol and health 2018. September 27.
      53% of the Western population regularly consume alcohol. Current drinkers consume on average 32.8 g alcohol per day, with the content of 1 standard drink ranging, depending on the country, from 8 g (eg, the United Kingdom
      National Health Service
      Alcohol units.
      ) to 14 g in the United States
      National Institute on Alcohol Abuse and Alcoholism
      What is a standard drink?.
      and ∼ 13.6 g in Canada
      Canadian Centre on Substance Use and Addiction
      Canada’s low-risk alcohol drinking guidelines.
      to 20 g in Austria.
      • Kalinowski A.
      • Humphreys K.
      Governmental standard drink definitions and low-risk alcohol consumption guidelines in 37 countries.
      Drinkers have increased their alcohol consumption since 2000 in almost all regions, while the prevalence of heavy episodic drinking (defined as ≥ 60 g alcohol on 1 occasion at least once per month) has decreased.
      Atrial fibrillation (AF) is the most common symptomatic arrhythmia worldwide, and the combination of an aging population and lifestyle factors, including alcohol consumption and its consequences, contribute to an increasing AF incidence (Fig. 1).
      • Griswold M.G.
      • Fullman N.
      • Hawley C.
      • et al.
      Alcohol use and burden for 195 countries and territories 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.
      ,
      • Tsao C.W.
      • Aday A.W.
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      • et al.
      Heart disease and stroke statistics—2022 update: a report from the American Heart Association.
      Interestingly, 35% of all AF patients identify alcohol consumption as an important trigger for their AF episodes, and AF as a consequence of consuming alcohol, the “holiday heart syndrome,”
      • Groh C.A.
      • Faulkner M.
      • Getabecha S.
      • et al.
      Patient-reported triggers of paroxysmal atrial fibrillation.
      remains a common reason for seeking professional help.
      • Hedden S.L.
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      • Lipari R.
      • et al.
      Behavioral health trends in the United States: results from the 2014 National Survey on Drug Use and Health (NSDUH).
      ,
      • Hansson A.
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      • Olsson S.B.
      Arrhythmia-provoking factors and symptoms at the onset of paroxysmal atrial fibrillation: a study based on interviews with 100 patients seeking hospital assistance.
      Excessive drinking has been clearly associated with a higher risk of AF, hypertension, obstructive sleep apnea (OSA), and obesity.
      • Roehrs T.
      • Roth T.
      Sleep, sleepiness, sleep disorders and alcohol use and abuse.
      ,
      • Fuchs F.D.
      • Fuchs S.C.
      The effect of alcohol on blood pressure and hypertension.
      Although a cardiovascular protective effect of smaller amounts of alcohol has been discussed for, eg, vascular disease, moderate levels of habitual consumption may be associated with AF. Accordingly, current consensus papers and management guidelines of several national and international societies recommend comprehensive management of lifestyle components, including avoidance of binge drinking and excessive alcohol consumption, to prevent AF onset and progression.
      • Benjamin E.J.
      • Al-Khatib S.M.
      • Desvigne-Nickens P.
      • et al.
      Research priorities in the secondary prevention of atrial fibrillation: a National Heart, Lung, and Blood Institute virtual workshop report.
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      • et al.
      2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design.
      Figure thumbnail gr1
      Figure 1World map: alcohol consumption vs atrial arrhythmia prevalence. (Top) Male alcohol consumer prevalence, %.
      • Griswold M.G.
      • Fullman N.
      • Hawley C.
      • et al.
      Alcohol use and burden for 195 countries and territories 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.
      (Bottom) Atrial fibrillation and flutter prevalence, per 100,000.
      • Chugh S.S.
      • Havmoeller R.
      • Narayanan K.
      • et al.
      Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 study.
      Of note, this figure represents a graphic illustration to visualise the association of atrial flutter/fibrillation prevalence and alcohol consumption, based on male alcohol consumer prevalence. This figure does not report on country-specific or sex-specific relationships.
      Herein, we review published reports on alcohol and AF, including pathophysiologic mechanisms, the role of binge drinking, habitual consumption at all levels, links between alcohol and other AF risk factors, and prognostic or therapeutic implications.

      Association Between Alcohol Consumption and AF

      Binge drinking and holiday heart syndrome

      The holiday heart syndrome was first introduced by Ettinger et al.
      • Ettinger P.O.
      • Wu C.F.
      • la Cruz C.D.
      • et al.
      Arrhythmias and the “holiday heart”: alcohol-associated cardiac rhythm disorders.
      in 1978, who described AF hospitalisation after weekend binge drinking in 24 patients. Even though some of these patients consumed alcohol regularly, subsequent investigations demonstrated that the holiday heart syndrome is not exclusive to habitual drinkers but can also happen in nondrinkers in the aftermath of a binge drinking episode.
      • Thornton J.R.
      Atrial fibrillation in healthy nonalcoholic people after an alcoholic binge.
      A definite time relation of alcohol consumption and AF genesis may be difficult to evaluate as some patients develop AF at the time of alcohol consumption, whereas others experience AF 12 to 36 hours after the binge drinking event.
      • Rich E.C.
      • Siebold C.
      • Campion B.
      Alcohol-related acute atrial fibrillation: a case-control study and review of 40 patients.
      AF usually ends within 24 hours after binge drinking, but one-third of patients may experience AF recurrences with subsequent binges.
      • Krishnamoorthy S.
      • Lip G.Y.H.
      • Lane D.A.
      Alcohol and illicit drug use as precipitants of atrial fibrillation in young adults: a case series and literature review.
      Scrutinising the dynamics of the holiday heart syndrome in large cohorts is difficult and has been to some extent ambiguous. In the MunichBREW (Munich Beer Related Electrocardiogram Workup) study, a study in which more than 3000 Oktoberfest visitors underwent breath alcohol concentration (BAC) measurements, increased BAC showed a predominant association with sinus tachycardia but not with AF.
      • Brunner S.
      • Herbel R.
      • Drobesch C.
      • et al.
      Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich Octoberfest: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW).
      A more recent study, in which more than 36,000 individuals were screened on several occasions throughout the year that are associated with heavy alcohol intake, high alcohol consumption was associated with increase in emergency department visits for AF or new onset of AF.
      • Aung S.
      • Nah G.
      • Vittinghoff E.
      • et al.
      Population-level analyses of alcohol consumption as a predictor of acute atrial fibrillation episodes.
      Other studies, however, found that binge drinking may be a less important risk factor for new-onset AF than regular habitual heavy drinking.
      • Liang Y.
      • Mente A.
      • Yusuf S.
      • et al.
      Alcohol consumption and the risk of incident atrial fibrillation among people with cardiovascular disease.
      ,
      • Kim Y.G.
      • Han K.D.
      • Choi J.I.
      • et al.
      Frequent drinking is a more important risk factor for new-onset atrial fibrillation than binge drinking: a nationwide population-based study.

      Habitual alcohol consumption

      Habitual alcohol consumption may outweigh hypertension or obesity as a risk factor for AF. In a population-based cohort study in Japanese communities (8602 participants), heavy drinking (> 69 g/day) was associated with a hazard ratio (HR) of developing AF of 2.68, compared with HRs of 1.72 for obesity and 1.02 for hypertension.
      • Sano F.
      • Ohira T.
      • Kitamura A.
      • et al.
      Heavy alcohol consumption and risk of atrial fibrillation: the Circulatory Risk in Communities Study (CIRCS).
      In another study of 26,163 participants, consuming more than 44 g/day was the strongest predicting parameter for AF, with an HR of 3.07, compared with HRs of 1.87 for obesity and 1.08 for hypertension.
      • Suzuki H.
      • Ohira T.
      • Takeishi Y.
      • et al.
      Increased prevalence of atrial fibrillation after the Great East Japan Earthquake: results from the Fukushima Health Management Survey.
      Three recent meta-analyses focused on the dose-dependent relationship between habitual alcohol consumption and new-onset AF risk.
      Larsson et al.
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      performed a meta-analysis of 7 prospective studies and reports on 859,420 people with a 12-year follow-up including 12,554 AF cases. After exclusion of binge drinkers and adjustment for other AF risk factors, relative risk (RR) for having AF was 1.08 after consumption of 12 g/day, increasing by additional 8% for each additional consumption of 12 g/day. In concordance with these results, Kodama et al.
      • Kodama S.
      • Saito K.
      • Tanaka S.
      • et al.
      Alcohol consumption and risk of atrial fibrillation: a meta-analysis.
      reported an incremental increase in RR of AF by 8% per 10 g alcohol consumption per day which was based on a meta-analysis of 14 retrospective and prospective studies. Samokhvalov et al.
      • Samokhvalov A.V.
      • Irving H.M.
      • Rehm J.
      Alcohol consumption as a risk factor for atrial fibrillation: a systematic review and meta-analysis.
      also reported a dose-dependent increase in AF risk for both women (RRs 1.07 for 24 g/day, 1.42 for 60 g/day, and 2.02 for 120 g/day) and men (RRs 1.08 for 24 g/day, 1.44 for 60 g/day, and 2.09 for 120 g/day).
      The relationship between chronic moderate-to-high alcohol consumption and incident AF is well established, but an increased AF risk has not been consistently demonstrated at low or increased levels of alcohol consumption.
      • Conen D.
      • Tedrow U.B.
      • Cook N.R.
      • et al.
      Alcohol consumption and risk of incident atrial fibrillation in women.
      • Schnabel R.B.
      • Yin X.
      • Gona P.
      • et al.
      50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study.
      • Conen D.
      • Albert C.M.
      Alcohol consumption and risk of atrial fibrillation: How much is too much?.
      • Mukamal K.J.
      • Tolstrup J.S.
      • Friberg J.
      • Jensen G.
      • Grønbæk M.
      Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study.
      • Shen J.
      • Johnson V.M.
      • Sullivan L.M.
      • et al.
      Dietary factors and incident atrial fibrillation: the Framingham Heart Study.
      • Gémes K.
      • Malmo V.
      • Laugsand L.E.
      • et al.
      Does moderate drinking increase the risk of atrial fibrillation? The Norwegian HUNT (Nord-Trøndelag Health) study.
      • Johansson C.
      • Lind M.M.
      • Eriksson M.
      • et al.
      Alcohol consumption and risk of incident atrial fibrillation: a population-based cohort study.
      • Frost L.
      • Vestergaard P.
      Alcohol and risk of atrial fibrillation or flutter: a cohort study.
      Although the study by Larsson et al.
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      suggested a significant 8% AF risk increase in people consuming > 12 g alcohol per day, no significant increase in AF risk was seen at similar levels in other meta-analyses.
      • Samokhvalov A.V.
      • Irving H.M.
      • Rehm J.
      Alcohol consumption as a risk factor for atrial fibrillation: a systematic review and meta-analysis.
      ,
      • Gallagher C.
      • Hendriks J.M.L.
      • Elliott A.D.
      • et al.
      Alcohol and incident atrial fibrillation—a systematic review and meta-analysis.
      In addition to the results of these meta-analyses, 2 recent analyses of large cohorts focused further on this topic. In the UK Biobank cohort, the relationship between alcohol and AF risk has been found to be J-shaped, suggesting the lowest AF risk at approximately 8 g alcohol per day. From this point, AF risk indicated an almost linear dose-dependent relationship toward every additional consumption of 8 g alcohol per day.
      • Tu S.J.
      • Gallagher C.
      • Elliott A.D.
      • et al.
      Risk thresholds for total and beverage-specific alcohol consumption and incident atrial fibrillation.
      However, these results contrast to a recent report of approximately 100,000 individuals pooled from different European cohorts suggesting a curvilinear relationship and increase in AF risk from very low alcohol levels.
      • Csengeri D.
      • Sprünker N.A.
      • di Castelnuovo A.
      • et al.
      Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance.
      Differences in sociocultural alcohol consumption patterns, ethnic-specific effects, or other residual confounders may explain the different results of these recent studies (Table 1).
      • Rich E.C.
      • Siebold C.
      • Campion B.
      Alcohol-related acute atrial fibrillation: a case-control study and review of 40 patients.
      ,
      • Liang Y.
      • Mente A.
      • Yusuf S.
      • et al.
      Alcohol consumption and the risk of incident atrial fibrillation among people with cardiovascular disease.
      ,
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      ,
      • Conen D.
      • Tedrow U.B.
      • Cook N.R.
      • et al.
      Alcohol consumption and risk of incident atrial fibrillation in women.
      ,
      • Mukamal K.J.
      • Tolstrup J.S.
      • Friberg J.
      • Jensen G.
      • Grønbæk M.
      Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study.
      ,
      • Frost L.
      • Vestergaard P.
      Alcohol and risk of atrial fibrillation or flutter: a cohort study.
      ,
      • Tu S.J.
      • Gallagher C.
      • Elliott A.D.
      • et al.
      Risk thresholds for total and beverage-specific alcohol consumption and incident atrial fibrillation.
      • Csengeri D.
      • Sprünker N.A.
      • di Castelnuovo A.
      • et al.
      Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance.
      • Qiao Y.
      • Shi R.
      • Hou B.
      • et al.
      Impact of alcohol consumption on substrate remodelling and ablation outcome of paroxysmal atrial fibrillation.
      • Marcus G.M.
      • Smith L.M.
      • Tseng Z.H.
      • et al.
      Alcohol intake is significantly associated with atrial flutter in patients under 60 years of age and a shorter right atrial effective refractory period.
      • Mukamal K.J.
      • Psaty B.M.
      • Rautaharju P.M.
      • et al.
      Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.
      • Planas F.
      • Romero-Menor C.
      • Vázquez-Oliva G.
      • Poblet T.
      • Navarro-López F.
      Natural history of and risk factors for idiopathic atrial fibrillation recurrence (FAP Registry).
      • Ruigómez A.
      • Johansson S.
      • Wallander M.A.
      • García Rodríguez L.A.
      Predictors and prognosis of paroxysmal atrial fibrillation in general practice in the UK.
      • Djoussé L.
      • Levy D.
      • Benjamin E.J.
      • et al.
      Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study.
      • Ruigómez A.
      • Johansson S.
      • Wallander M.A.
      • Rodríguez L.A.G.
      Incidence of chronic atrial fibrillation in general practice and its treatment pattern.
      • Wilhelmsen L.
      • Rosengren A.
      • Lappas G.
      Hospitalisations for atrial fibrillation in the general male population: morbidity and risk factors.
      • Krahn A.D.
      • Manfreda J.E.
      • Tate R.B.
      • et al.
      The natural history of atria1 fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study.
      • Cohen E.J.
      • Klatsky A.L.
      • Armstrong M.A.
      Alcohol use and supraventricular arrhythmia.
      • Koskinen P.
      • Kupari M.
      • Leinonen H.
      • Luomanmaki K.
      Alcohol and new onset atrial fibrillation: a case-control study of a current series.
      Table 1Studies investigating the effect of alcohol consumption on atrial fibrillation and flutter
      Authors (year)refAF/AFL, nSex, % femaleAge, yFollow-up, yStudy designAF ascertainmentConclusion
      Tu et al. (2021)
      • Tu S.J.
      • Gallagher C.
      • Elliott A.D.
      • et al.
      Risk thresholds for total and beverage-specific alcohol consumption and incident atrial fibrillation.
      21,312/403,2815240-6911.4UK population-based prospective cohortMedical recordsLow alcohol intake (< 7 UK-SD/wk) was associated with lowest AF risk.
      Csengeri et al. (2021)
      • Csengeri D.
      • Sprünker N.A.
      • di Castelnuovo A.
      • et al.
      Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance.
      5854/107,8455224-9713.9Community-based pooled cohortQuestionnaire, medical recordsModerate alcohol intake (> 8 US-SD/week) was associated with increased AF risk.
      Qiao et al. (2015)
      • Qiao Y.
      • Shi R.
      • Hou B.
      • et al.
      Impact of alcohol consumption on substrate remodelling and ablation outcome of paroxysmal atrial fibrillation.
      40/1222646-651.8Prospective observationalECG, 3-monthly 7-day HolterAlcohol intake after PVI predicted recurrent AF: recurrence rates 64.9% for women > 7 US-SD/wk and men > 14 US-SD/wk), 30.8% for women ≤ 7 SD/wk and men ≤ 14 US-SD/wk, and 18.7% for abstainers.
      Larsson et al. (2014)
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      6019/68,8483845-8312Population-based prospective cohortRegistryDose-dependent increase in AF/AFL risk: RRs 1.12 for 7-14 US-SD/wk, 1.18 for 15-21 US-SD/wk, and 1.43 for > 21 US-SD/wk. Only wine and liquor increased the risk.
      Liang et al. (2012)
      • Liang Y.
      • Mente A.
      • Yusuf S.
      • et al.
      Alcohol consumption and the risk of incident atrial fibrillation among people with cardiovascular disease.
      2093/30,43330> 554.7Review of two antihypertensive randomised controlled trialsECG, questionnaireLow to moderate intake (women ≤ 14 US-SD/wk, men ≤ 21 US-SD/wk) was associated with increase in AF risk in patients with cardiovascular disease (HR 1.14, 95% CI 1.04-1.26).
      Marcus et al. (2008)
      • Marcus G.M.
      • Smith L.M.
      • Tseng Z.H.
      • et al.
      Alcohol intake is significantly associated with atrial flutter in patients under 60 years of age and a shorter right atrial effective refractory period.
      195/3912532-71Case-controlMedical recordsAlcohol intake was associated with AFL in younger patients. AF/AFL patients were more likely to by daily drinkers (27% vs 14%; P = 0.001).
      Conen et al. (2008)
      • Conen D.
      • Tedrow U.B.
      • Cook N.R.
      • et al.
      Alcohol consumption and risk of incident atrial fibrillation in women.
      653/34,71510045-6012.4Population-based prospective cohortECG, medical recordsModerate to high alcohol intake (≥ 14 US-SD/wk) increased AF risk compared with abstainers (HR 1.49, 95% CI 1.05-2.11).
      Mukamal et al. (2007)
      • Mukamal K.J.
      • Psaty B.M.
      • Rautaharju P.M.
      • et al.
      Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.
      1232/56095067-809.1Population-based prospective cohortECG, registry, medical recordsHabitual alcohol intake (all levels) did not increase risk of AF or death, but former drinking identifies people at higher risk of AF diagnosis.
      Planas et al. (2006)
      • Planas F.
      • Romero-Menor C.
      • Vázquez-Oliva G.
      • Poblet T.
      • Navarro-López F.
      Natural history of and risk factors for idiopathic atrial fibrillation recurrence (FAP Registry).
      32/1153659 ± 142.6Prospective observationalECGLow to moderate alcohol intake (women < 12 US-SD/wk, men < 23 US-SD/wk) significantly predicted AF recurrence in patients with previous AF (50% vs 24%; P = 0.01).
      Ruigómez et al. (2005)
      • Ruigómez A.
      • Johansson S.
      • Wallander M.A.
      • García Rodríguez L.A.
      Predictors and prognosis of paroxysmal atrial fibrillation in general practice in the UK.
      70/4185140-892.7Prospective observationalECG, medical recordsModerate to high alcohol intake (> 14 SD/wk) increased the risk of progression from paroxysmal AF to “chronic AF” by 3-fold.
      Mukamal et al. (2005)
      • Mukamal K.J.
      • Tolstrup J.S.
      • Friberg J.
      • Jensen G.
      • Grønbæk M.
      Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study.
      1071/16,4155426-7516.3Population-based prospective cohortECG, registry, medical recordsHigh alcohol intake (> 35 US-SD/wk) increased AF/AFL risk in men (HR 1.45, 95% CI 1.02-2.04). Moderate alcohol intake did not increase risk of AF/AFL.
      Frost et al. (2004)
      • Frost L.
      • Vestergaard P.
      Alcohol and risk of atrial fibrillation or flutter: a cohort study.
      556/47,9494350-645.7Hospital-based prospective cohortRegistryModerate alcohol intake (∼12 US-SD/wk) increased AF/AFL risk in men (HR 1.44, 95% CI 1.04-2.01).
      Djoussé et al. (2004)
      • Djoussé L.
      • Levy D.
      • Benjamin E.J.
      • et al.
      Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study.
      1055/46724828-62>50Population-based prospective cohortECG, medical recordsHigh alcohol intake (> 21 US-SD/wk) increased AF/AFL-risk by 34% (multivariate-adjusted RR 1.34, 95% CI 1.01-1.78). Long-term moderate alcohol intake (< 21 US-SD/wk) showed little association with AF risk.
      Ruigómez et al. (2002)
      • Ruigómez A.
      • Johansson S.
      • Wallander M.A.
      • Rodríguez L.A.G.
      Incidence of chronic atrial fibrillation in general practice and its treatment pattern.
      1035/60355340-89Nested case-controlECG, Holter, echocardiographyHigh alcohol intake (> 28 SD/wk) increased risk of developing chronic AF (adjusted RR 2.4, 95% CI 1.4-4.1).
      Wilhelmsen et al. (2001)
      • Wilhelmsen L.
      • Rosengren A.
      • Lappas G.
      Hospitalisations for atrial fibrillation in the general male population: morbidity and risk factors.
      754/7495047-5525.2Population-based prospective cohortRegistry“Alcohol abuse” (quantity unspecified) increased the risk of future AF hospitalisation (OR 1.21, 95% CI 1.02-1.42).
      Krahn et al. (1995)
      • Krahn A.D.
      • Manfreda J.E.
      • Tate R.B.
      • et al.
      The natural history of atria1 fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study.
      299/3983018-6244Population-based prospective cohortECG, medical report“Alcoholism” (quantity unspecified) increased AF risk (RR 2.07, 95% CI 1.38-3.10).
      Cohen et al. (1988)
      • Cohen E.J.
      • Klatsky A.L.
      • Armstrong M.A.
      Alcohol use and supraventricular arrhythmia.
      42/3966Retrospective cohortMedical recordsHigh alcohol intake (> 42 US-SD/wk) increased AF (RR 2.3) and AFL risk (RR 3.0), compared with low alcohol intake (< 7 US-SD/wk (P < 0.05 for both groups).
      Koskinen et al. (1987)
      • Koskinen P.
      • Kupari M.
      • Leinonen H.
      • Luomanmaki K.
      Alcohol and new onset atrial fibrillation: a case-control study of a current series.
      100/2001821-64Case-controlECGAF patients were significantly more likely to have consumed alcohol within 2 days of AF onset compared with control subjects, with the highest mean daily alcohol intake in the “lone-AF” patients.
      Rich et al. (1985)
      • Rich E.C.
      • Siebold C.
      • Campion B.
      Alcohol-related acute atrial fibrillation: a case-control study and review of 40 patients.
      58/1162418-70Case-controlMedical recordsHigh alcohol intake (> 32 US-SD/wk) was more likely in AF patients than in control subjects, and alcohol withdrawal was more common in patients with alcohol-related AF.
      AF, atrial fibrillation; AFL, atrial flutter; CI, confidence interval; ECG, electrocardiography; HR, hazard ratio; N/A, not available; OR, odds ratio; PVI, pulmonary vein isolation; RR, relative risk; UK-SD, standard drink defined in the UK as 8 g alcohol; US-SD, standard drink defined in the US as 12 g alcohol.
      The interpretation of large population-based observational studies is associated with relevant limitations. Firstly, the quantity of alcohol consumption was mainly determined by self-reporting, rather than by objective blood or urine samples or mHealth-supported alcohol consumption tracking, which may result in under-reporting of alcohol consumption and subsequently an imprecise estimation of alcohol-related AF risk. Second, AF monitoring differed among the studies, which increases the bias of detecting symptomatic AF, triggering additional electrocardiographic (ECG) recordings, high-burden AF during scheduled ECG recordings, and AF associated with hospital admissions.
      Of note, the correlation between alcohol consumption and AF is usually reported as RR as most studies compare alcohol consumers with non–alcohol consumers. However, to contextualise relevance of reported numbers and especially RRs, absolute risks are of crucial importance and should be reported and discussed in future studies.

      Beverage-specific relationship between alcohol and AF

      According to WHO’s Global Status Report on Alcohol,
      World Health Organization
      Global status report on alcohol and health 2018. September 27.
      44.8% of alcohol worldwide is consumed in the form of spirits. The second most consumed type of beverage is beer (34.3%), followed by wine (11.7%). How different alcoholic beverages contribute to AF risk is uncertain. Larsson et al.
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      reported that of those consuming > 14 standard drinks/week, only wine and liquor, and not beer, were associated with increased AF risk. Tu et al.
      • Tu S.J.
      • Gallagher C.
      • Elliott A.D.
      • et al.
      Risk thresholds for total and beverage-specific alcohol consumption and incident atrial fibrillation.
      found in the UK Biobank cohort that low-to-moderate levels of red and white wine intake appeared to be associated with significantly lower risks of AF, whereas any intake of beer/cider and spirits seemed to be associated with harm.
      • Tu S.J.
      • Gallagher C.
      • Elliott A.D.
      • et al.
      Risk thresholds for total and beverage-specific alcohol consumption and incident atrial fibrillation.
      However, other studies reported no significant increase in risk with these types of beverages.
      • Mukamal K.J.
      • Tolstrup J.S.
      • Friberg J.
      • Jensen G.
      • Grønbæk M.
      Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study.
      ,
      • Mukamal K.J.
      • Psaty B.M.
      • Rautaharju P.M.
      • et al.
      Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.
      Similar factors as mentioned previously may have contributed to the variable results concerning beverage-specific atrial arrhythmogenic risk. We mention here potential confounding associations with differences in the socioeconomic status of the investigated cohorts, the higher alcohol concentration of wine and liquor, differences in consumer behaviour between drinkers of different beverages,
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      and confounders such as differences in AF risk factors or other nonreported lifestyle components. The heterogeneity of the aforementioned body of data poses a challenging problem in analysing meta-analyses and thence in drawing definite conclusions.

      Sex-specific relationship between alcohol and AF

      Some,
      • Frost L.
      • Vestergaard P.
      Alcohol and risk of atrial fibrillation or flutter: a cohort study.
      ,
      • Gallagher C.
      • Hendriks J.M.L.
      • Elliott A.D.
      • et al.
      Alcohol and incident atrial fibrillation—a systematic review and meta-analysis.
      but not all,
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      ,
      • Mukamal K.J.
      • Tolstrup J.S.
      • Friberg J.
      • Jensen G.
      • Grønbæk M.
      Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study.
      ,
      • Csengeri D.
      • Sprünker N.A.
      • di Castelnuovo A.
      • et al.
      Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance.
      studies showed a greater risk of incident AF in men consuming alcohol. Several studies could not show an increase in AF risk across all alcohol levels in women.
      • Johansson C.
      • Lind M.M.
      • Eriksson M.
      • et al.
      Alcohol consumption and risk of incident atrial fibrillation: a population-based cohort study.
      ,
      • Frost L.
      • Vestergaard P.
      Alcohol and risk of atrial fibrillation or flutter: a cohort study.
      ,
      • Tolstrup J.S.
      • Wium-Andersen M.K.
      • Ørsted D.D.
      • Nordestgaard B.G.
      Alcohol consumption and risk of atrial fibrillation: observational and genetic estimates of association.
      ,
      • Cha M.J.
      • Oh G.C.
      • Lee H.
      • et al.
      Alcohol consumption and risk of atrial fibrillation in asymptomatic healthy adults.
      Importantly, most of these previous studies included only a few women consuming high levels of alcohol. In a recent analysis of the large UK Biobank cohort, with balanced sexes and a sufficient number of women in the high level of alcohol consumption group, associations of alcohol and arrhythmias in both men and women were reported.
      • Tu S.J.
      • Gallagher C.
      • Elliott A.D.
      • et al.
      Risk thresholds for total and beverage-specific alcohol consumption and incident atrial fibrillation.
      However, a sex-specific association could be reported for alcohol consumption and established AF risk factors, such as hypertension.
      • Roerecke M.
      • Tobe S.W.
      • Kaczorowski J.
      • et al.
      Sex-specific associations between alcohol consumption and incidence of hypertension: a systematic review and meta-analysis of cohort studies.

      Alcohol and AF ablation outcome

      In 50 patients with persistent AF undergoing pulmonary vein isolation, higher body mass index and excess alcohol consumption were the only significant factors associated with atrial tachyarrhythmia recurrence.
      • Hussein A.
      • Das M.
      • Riva S.
      • et al.
      Use of ablation index–guided ablation results in high rates of durable pulmonary vein isolation and freedom from arrhythmia in persistent atrial fibrillation patients.
      In addition, in 1361 consecutive patients with paroxysmal AF who underwent catheter ablation, including 623 (45.8%) who consumed alcohol, the frequency of alcohol consumption was significantly associated with a 7% increase in AF recurrence (HR 1.07) after catheter ablation for each day per week that alcohol was consumed.
      • Takigawa M.
      • Takahashi A.
      • Kuwahara T.
      • et al.
      Impact of alcohol consumption on the outcome of catheter ablation in patients with paroxysmal atrial fibrillation.
      In 122 patients with symptomatic paroxysmal AF, daily alcohol consumption was associated with atrial remodelling, and the success ratse for cardioversion were 81.3%, 69.2%, and 35.1% in alcohol abstainers, moderate drinkers, and heavy drinkers, respectively.
      • Qiao Y.
      • Shi R.
      • Hou B.
      • et al.
      Impact of alcohol consumption on substrate remodelling and ablation outcome of paroxysmal atrial fibrillation.
      However, in a retrospective analysis of 226 consecutive patients undergoing first-time pulmonary vein isolation, alcohol consumption was not associated with early or late AF recurrence.
      • Barham W.Y.
      • Sauer W.H.
      • Fleeman B.
      • et al.
      Impact of alcohol consumption on atrial fibrillation outcomes following pulmonary vein isolation.

      Effect of alcohol abstinence

      As stated in WHO’s “Global Status Report on Alcohol,” a 10% relative reduction of total per-capita consumption was achieved within 6 years in the WHO European Region, demonstrating the feasibility of such an endeavour.
      World Health Organization
      Global status report on alcohol and health 2018. September 27.
      Most of the current data suggest a relatively linear relationship between alcohol consumption and new-onset AF, and based on observational and nonrandomised studies, a safe level of daily alcohol intake in patients with a history of AF likely may not exist. Among former drinkers in the Atherosclerosis Risk in Communities Study (ARIC),
      • Dixit S.
      • Alonso A.
      • Vittinghoff E.
      • et al.
      Past alcohol consumption and incident atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) Study.
      a longer duration of abstinence was associated with a decreased risk of AF. In another analysis of patients with newly diagnosed type 2 diabetes from the Korean National Health Insurance Service database, alcohol abstinence was associated with a low risk of AF development.
      • jung Choi Y.
      • Han K.D.
      • Choi E.K.
      • et al.
      Alcohol abstinence and the risk of atrial fibrillation in patients with newly diagnosed type 2 diabetes mellitus: a nationwide population-based study.
      In a recent randomised intervention study, 140 adults with paroxysmal or persistent AF, who consumed 10 or more standard drinks per week, were randomised to either abstain from alcohol or continue their usual alcohol consumption. AF recurrence and AF burden, over 6 months of follow-up, was significantly lower in the abstinence group than in the control group.
      • Voskoboinik A.
      • Kalman J.M.
      • de Silva A.
      • et al.
      Alcohol abstinence in drinkers with atrial fibrillation.
      Reduction in alcohol consumption and alcohol abstinence also improves established AF risk factors, such as hypertension,
      • Roerecke M.
      • Kaczorowski J.
      • Tobe S.W.
      • et al.
      The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis.
      obesity, and sleep-disordered breathing,
      • Roehrs T.
      • Roth T.
      Sleep, sleepiness, sleep disorders and alcohol use and abuse.
      ,
      • Powell-Wiley T.M.
      • Poirier P.
      • Burke L.E.
      • et al.
      Obesity and cardiovascular disease: a scientific statement from the American Heart Association.
      and therefore represents an important component of recent AF risk factor and lifestyle modification intervention. In addition, alcohol abstinence has been associated with a lower risk of stroke in patients with incident AF.
      • Lee S.R.
      • Choi E.K.
      • Jung J.H.
      • et al.
      Lower risk of stroke after alcohol abstinence in patients with incident atrial fibrillation: a nationwide population-based cohort study.

      Alcohol withdrawal syndrome

      Sudden cessation of a heavy drinking habit may lead to the alcohol withdrawal syndrome (AWS), which is associated with both atrial and ventricular arrhythmia. AWS and its association with AF and in-hospital mortality was investigated in 2 large retrospective analyses. Thakkar et al.
      • Thakkar S.
      • Patel H.P.
      • Boppana L.K.T.
      • et al.
      Arrhythmias in patients with in-hospital alcohol withdrawal are associated with increased mortality: insights from 1.5 million hospitalisations for alcohol withdrawal syndrome.
      reported an arrhythmia incidence of 9.72%, 66.7% of which were AF, in more than 1.5 million hospitalisations for AWS. Similar numbers were reported by Reddy et al.,
      • Reddy V.
      • Adegbala O.
      • Ando T.
      • et al.
      Comparison of in-hospital outcomes of patients with-versus-without atrial fibrillation and alcohol withdrawal syndrome.
      who found a 5.2% AF history in 280,541 patients with AWS. Moreover, patients with both AWS and arrhythmias had higher in-hospital mortality and were associated with acute heart failure, kidney injury, and a longer more expensive hospital stay.
      • Thakkar S.
      • Patel H.P.
      • Boppana L.K.T.
      • et al.
      Arrhythmias in patients with in-hospital alcohol withdrawal are associated with increased mortality: insights from 1.5 million hospitalisations for alcohol withdrawal syndrome.
      ,
      • Reddy V.
      • Adegbala O.
      • Ando T.
      • et al.
      Comparison of in-hospital outcomes of patients with-versus-without atrial fibrillation and alcohol withdrawal syndrome.
      However, studying AWS and AF remains challenging owing to confounding interference and the retrospective nature of most studies.

      Pathophysiology

      The occurrence of AF triggers is promoted by alcohol due to both increased autonomic imbalance and direct acute atrial electrophysiologic effects, which result in shortened atrial action potentials, increased dispersion of refractoriness, and slowed intra-atrial conduction (Fig. 2 and Table 2).
      • Yan J.
      • Thomson J.K.
      • Zhao W.
      • et al.
      Role of stress kinase JNK in binge alcohol–evoked atrial arrhythmia.
      • Zhang H.
      • Ruan H.
      • Rahmutula D.
      • et al.
      Effect of acute and chronic ethanol on atrial fibrillation vulnerability in rats.
      • Zhao Y.
      • Sun J.
      • Hu J.
      • Bo N.
      • Yu B.
      Effect of ethanol and its metabolites on acetylcholine-sensitive K+ channel Kir3.1 protein expression of neonatal rat primary atrial cardiomyocytes.
      Long-term alcohol consumption facilitates an atrial cardiomyopathy resembling atrial structural, functional, and electrical remodelling processes, thereby stabilising AF episodes and contributing to AF progression (Table 2).
      • Piano M.R.
      • Rosenblum C.
      • Solaro R.J.
      • Schwertz D.
      Calcium sensitivity and the effect of the calcium sensitising drug pimobendan in the alcoholic isolated rat atrium.
      • Ettinger P.O.
      • Lyons M.
      • Oldewurtel H.A.
      • Regan T.J.
      Cardiac conduction abnormalities produced by chronic alcoholism.
      • Mcmanus D.D.
      • Yin X.
      • Gladstone R.
      • et al.
      Alcohol consumption, left atrial diameter, and atrial fibrillation.
      Moreover, pathomechanisms of alcohol consumption are linked with AF-associated comorbidities such as excess weight, sleep-disordered breathing, and hypertension, which potentially lead to further AF substrate perpetuation. Several transient arrhythmogenic changes during binge drinking may result in the holiday heart syndrome (Fig. 3).
      Figure thumbnail gr2
      Figure 2Arrhythmogenic mechanisms of alcohol. The electrophysiologic, cellular, autonomic, and atrial structural effects caused by acute alcohol consumption. AERP, atrial effective refractory period; AV, atrioventricular; HR, heart rate; HRV, heart rate variability; LA, left atrial.
      Table 2Studies investigating the effect of acute or chronic alcohol consumption on cardiac electrophysiology
      Author (year)refStudy design/interventionPopulationSpeciesConclusions
      Acute and intermediate arrhythmogenic effects
      Anadon et al. (1996)
      • Anadon M.J.
      • Almendral J.
      • González P.
      • et al.
      Alcohol concentration determines the type of atrial arrhythmia induced in a porcine model of acute alcoholic intoxication.
      Alcohol infusion, IV, blood level 100-200 mg/dL16PigInfusion of alcohol shortened action potential and increased AF susceptibility, following burst pacing of the atria.
      Zhang et al. (2020)
      • Zhang H.
      • Ruan H.
      • Rahmutula D.
      • et al.
      Effect of acute and chronic ethanol on atrial fibrillation vulnerability in rats.
      Explanted hearts in a Langendorff preparation, perfused with ethanol20RodentAdministration of alcohol dose-dependently decreased atrial refractory periods, decreased atrial conduction in both atria, and increased dispersion of atrial refractoriness.
      Zhao et al. (2015)
      • Zhao Y.
      • Sun J.
      • Hu J.
      • Bo N.
      • Yu B.
      Effect of ethanol and its metabolites on acetylcholine-sensitive K+ channel Kir3.1 protein expression of neonatal rat primary atrial cardiomyocytes.
      Patch-clamp on isolated atrial cardiomyocytes from newborn rats150RodentExposure to ethanol and acetaldehyde (its metabolite) induced significant up-regulation in Kir3.1 (IK,ACh).
      Laszlo et al. (2009)
      • Laszlo R.
      • Eick C.
      • Schwiebert M.
      • et al.
      Alcohol-induced electrical remodelling: effects of sustained short-term ethanol infusion on ion currents in rabbit atrium.
      Alcohol infusion, IV, over 5 days8RabbitSignificant reduction in L-type calcium (ICa,L) and sodium (INa) current density.
      Chen et al. (2004)
      • Chen Y.C.
      • Chen S.A.
      • Chen Y.J.
      • et al.
      Effect of ethanol on the electrophysiological characteristics of pulmonary vein cardiomyocytes.
      Isolated pulmonary vein cardiomyocytes, incubated in ethanol (0.3 or 1 mg/mL) over 30 minutes56RabbitShortening of pulmonary vein action potential duration, mediated by increased Ito outward potassium current activity, without altering automaticity.
      Gould et al. (1978)
      • Gould L.
      • Reddy C.V.
      • Becker W.
      • Oh K.C.
      • Kim S.G.
      Electrophysiologic properties of alcohol in man.
      Intake of 5 standard drinks of whiskey14HumanConduction delay in the atria, improved conduction via the AV node, and shortening of ventricular refractory period.
      Marcus et al. (2021)
      • Marcus G.M.
      • Vittinghoff E.
      • Whitman I.R.
      • et al.
      Acute consumption of alcohol and discrete atrial fibrillation events.
      Prospective, case-crossover analysis over 4 weeks in patients with documented paroxysmal AF, who consumed ≥ 1 standard drinks per week100HumanThe odds of having an AF episode were 2-fold higher after 1 drink and 3-fold higher after ≥ 2 drinks within 4 hours.
      Marcus et al. (2021)
      • Marcus G.M.
      • Dukes J.W.
      • Vittinghoff E.
      • et al.
      A randomized, double-blind, placebo- controlled trial of intravenous alcohol to assess changes in atrial electrophysiology.
      Randomised, double-blinded, placebo-controlled trial, IV alcohol titrated to a blood alcohol concentration of 0.08%.100HumanShortening of the atrial effective refractory periods, especially in the pulmonary veins with an average of 12 ms.
      Greenspon et al. (1983)
      • Greenspon A.J.
      • SCHAAL S.F.
      The “holiday heart”: electrophysiologic studies of alcohol effects in alcoholics.
      Habitual heavy drinkers (consumption of 6 standard drinks of whiskey14HumanProlongation of bundle of His conduction and shortened sinus node recovery time; associated with increased inducibility of atrial or ventricular arrhythmias (in 71% of participants).
      Steinbigler et al. (2003)
      • Steinbigler P.
      • Haberl R.
      • König B.
      • Steinbeck G.
      P-Wave signal averaging identifies patients prone to alcohol-induced paroxysmal atrial fibrillation.
      Binge drinking episodes in patients with history of AF, age-matched with control subjects55HumanProlongation of interatrial conduction (P-wave duration).
      Sengul et al. (2011)
      • Sengul C.
      • Cevik C.
      • Ozveren O.
      • et al.
      Acute alcohol consumption is associated with increased interatrial electromechanical delay in healthy men.
      Recordings measured 1 hour after intake of 76.8 g ethanol in patients with no history of AF30HumanAn acute moderate intake of alcohol induced prolongation of P-wave duration and slowing of interatrial electromechanical delay, and expressed increased susceptibility to AF.
      Atrial cardiomyopathy/structural effects
      Piano et al. (1999)
      • Piano M.R.
      • Rosenblum C.
      • Solaro R.J.
      • Schwertz D.
      Calcium sensitivity and the effect of the calcium sensitising drug pimobendan in the alcoholic isolated rat atrium.
      Two months of alcohol consumption with alcohol (9% vol/vol) liquid diet18RodentDecrease in myofibrillar response to calcium, and altered responsiveness to inotropes.
      Zhang et al. (2020)
      • Zhang H.
      • Ruan H.
      • Rahmutula D.
      • et al.
      Effect of acute and chronic ethanol on atrial fibrillation vulnerability in rats.
      6 months of alcohol (20% ethanol) consumption28RodentSlowing of atrial conduction, shortening of atrial refractoriness, increased dispersion of refractoriness, and decrease in conduction velocity in both atria. Chronic alcohol intake affected expression changes of KCNA5 and KCNQ1, and abnormal expression of Cx40 in the right atrium.
      Voskoboinik et al. (2019)
      • Voskoboinik A.
      • Wong G.
      • Lee G.
      • et al.
      Moderate alcohol consumption is associated with atrial electrical and structural changes: Insights from high-density left atrial electroanatomic mapping.
      Drinkers compared with nondrinkers, enrolled for AF ablation75HumanShortening of atrial effective refractory periods, and lower bipolar global voltages, complex atrial potentials, and slowing of atrial conduction velocity revealed by electroanatomic mapping.
      Qiao et al. (2015)
      • Qiao Y.
      • Shi R.
      • Hou B.
      • et al.
      Impact of alcohol consumption on substrate remodelling and ablation outcome of paroxysmal atrial fibrillation.
      Population undergoing pulmonary vein isolation144HumanIncreased probability of regional low voltages increased by 10% for every standard drink consumed. Alcohol consumption was associated with poor ablation outcome after PVI.
      Ettinger et al. (1976)
      • Ettinger P.O.
      • Lyons M.
      • Oldewurtel H.A.
      • Regan T.J.
      Cardiac conduction abnormalities produced by chronic alcoholism.
      7-33 months of alcohol (15%-30% ethanol) diluted in drinking water41DogProlongation in conduction from bundle of His to ventricular activation time (H-Q) and a widening of the QRS. The duration of alcohol intake correlated with H-Q and QRS alteration. Localised dilation and cystic changes in intercalated discs.
      Voskoboinik et al. (2018)
      • Voskoboinik A.
      • Costello B.T.
      • Kalman E.
      • et al.
      Regular alcohol consumption is associated with impaired atrial mechanical function in the atrial fibrillation population: a cross-sectional MRI-based study.
      and (2019)
      • Voskoboinik A.
      • Costello B.T.
      • la Gerche A.
      • et al.
      Relation of alcohol consumption to left ventricular fibrosis using cardiac magnetic resonance imaging.
      2018: prospective study in patients with AF;

      2019: prospective study in patients undergoing 3T CMR with ventricular T1 mapping
      2018: 160; 2019: 165HumanAlcohol consumption was associated with increased left atrial size and atrial mechanical dysfunction. Second study showed association with T1 changes suggesting a reduction in diffuse ventricular fibrosis.
      Mcmanus et al. (2016)
      • Mcmanus D.D.
      • Yin X.
      • Gladstone R.
      • et al.
      Alcohol consumption, left atrial diameter, and atrial fibrillation.
      and Singh et al. (2013)
      • Singh K.J.
      • Cohen B.E.
      • Na B.
      • et al.
      Alcohol consumption and 5-year change in left atrial volume among patients with coronary heart disease: results from the Heart and Soul Study.
      2016: prospective cohort analysis of Offspring and Original Framingham Study;

      2013: prospective cohort study in patients with coronary heart diseases
      2016: 5220; 2013: 601HumanAlcohol consumption was a predictor for enlarged left atria and subsequent AF incidents.
      Zagrosek et al. (2010)
      • Zagrosek A.
      • Messroghli D.
      • Schulz O.
      • Dietz R.
      • Schulz-Menger J.
      Effect of binge drinking on the heart as assessed by cardiac magnetic resonance imaging.
      Excessive consumption of alcohol over a short time period31HumanTransient increase in ventricular T2-signal intensity, indicating myocardial edema. Global relative enhancement was consistent with hyperemia. Troponin elevation suggested acute inflammation.
      AF, atrial fibrillation; AV, atrioventricular; CMR, cardiac magnetic resonance; IV, intravenous; PVI, pulmonary vein isolation.
      Figure thumbnail gr3
      Figure 3Dynamic arrhythmogenic substrate development. Development of a progressive arrhythmogenic substrate (blue line) due to concomitant atrial fibrillation (AF) risk factors such as hypertension, sleep-disordered breathing, cardiomyopathy, and chronic alcohol consumption. Several transient arrhythmogenic changes during binge drinking (orange line) result in the holiday heart syndrome. The AF risk threshold is indicated by the black dashed line.

      Acute and intermediate arrhythmogenic effects of alcohol consumption

      Studies using a broad range of nonhuman animal models have reported on alcohol-related atrial arrhythmogenesis in the setting of alcohol consumption. In a porcine model, acute alcohol infusion shortened the atrial action potential and increased AF susceptibility after atrial burst pacing.
      • Anadon M.J.
      • Almendral J.
      • González P.
      • et al.
      Alcohol concentration determines the type of atrial arrhythmia induced in a porcine model of acute alcoholic intoxication.
      As reported in a rat model, the increased AF inducibility due to alcohol administration was found to be dose dependent, and atrial electrophysiologic responses to alcohol included decreased atrial refractory periods, increased dispersion of atrial refractoriness, and a decreased atrial conduction velocity in both atria.
      • Zhang H.
      • Ruan H.
      • Rahmutula D.
      • et al.
      Effect of acute and chronic ethanol on atrial fibrillation vulnerability in rats.
      Another study in rats reported an up-regulation in protein expression of the acetylcholine-sensitive potassium channel Kir3.1 (IK,ACh), following 24 hours of exposure to ethanol and its metabolite acetaldehyde. Increased IK,ACh activity, which promotes repolarisation, might be one explanatory pathway for shortened action potentials in the presence of ethanol.
      • Zhao Y.
      • Sun J.
      • Hu J.
      • Bo N.
      • Yu B.
      Effect of ethanol and its metabolites on acetylcholine-sensitive K+ channel Kir3.1 protein expression of neonatal rat primary atrial cardiomyocytes.
      Furthermore, direct electrophysiologic effects on ion channels were described in rabbits, in which a 5-day alcohol infusion significantly reduced L-type calcium (ICa,L) and sodium (INa) current density.
      • Laszlo R.
      • Eick C.
      • Schwiebert M.
      • et al.
      Alcohol-induced electrical remodelling: effects of sustained short-term ethanol infusion on ion currents in rabbit atrium.
      Moreover, alcohol administration shortened pulmonary vein action potential duration mediated by increased Ito outward potassium current activity in rabbit pulmonary vein cardiomyocytes. This happened without altering automaticity or triggered activity.
      • Chen Y.C.
      • Chen S.A.
      • Chen Y.J.
      • et al.
      Effect of ethanol on the electrophysiological characteristics of pulmonary vein cardiomyocytes.
      More recently, Wang et al.
      • Wang Y.
      • Morishima M.
      • Li D.
      • et al.
      Binge alcohol exposure triggers atrial fibrillation through T-type Ca2+ channel upregulation via protein kinase C (PKC)/glycogen synthesis kinase 3β (GSK3β)/nuclear factor of activated T-cells (NFAT) signalling—an experimental account of holiday heart syndrome.
      investigated cellular pathways after an alcohol binge. In an in vitro analysis, they found an ethanol-induced up-regulation of T-type calcium channels explaining increased trigger formation and a possible molecular pathway of the holiday heart syndrome.
      In humans, acute cardiac effects of alcohol were initially described in 14 patients undergoing electrophysiologic examinations. In that study, 5 standard drinks of whiskey resulted in a shortening in the atrial refractory period and slowed intra-atrial conduction.
      • Gould L.
      • Reddy C.V.
      • Becker W.
      • Oh K.C.
      • Kim S.G.
      Electrophysiologic properties of alcohol in man.
      More recently, Marcus et al.
      • Marcus G.M.
      • Vittinghoff E.
      • Whitman I.R.
      • et al.
      Acute consumption of alcohol and discrete atrial fibrillation events.
      demonstrated that recent alcohol consumption was associated with increased individual AF episodes in 100 patients fitted with a continuous ECG monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. The authors found a 2-fold higher odds for having an AF episode after 1 alcoholic drink and a 3-fold higher odds after 2 or more drinks within 4 hours. In addition, in 100 participants, Marcus et al.
      • Marcus G.M.
      • Dukes J.W.
      • Vittinghoff E.
      • et al.
      A randomized, double-blind, placebo- controlled trial of intravenous alcohol to assess changes in atrial electrophysiology.
      showed that intravenous alcohol titrated to 0.08% blood alcohol concentration decreased pulmonary vein atrial effective refractory periods by an average of 12 ms.
      Alcohol consumption may also prolong the His ventricular (H-V) interval and shorten sinus node recovery time, as shown in habitual moderate-heavy consumers. This was associated with increased inducibility of atrial or ventricular arrhythmias in 71% of the participants.
      • Greenspon A.J.
      • SCHAAL S.F.
      The “holiday heart”: electrophysiologic studies of alcohol effects in alcoholics.
      Moreover, in patients with a history of AF after a binge-drinking episode, interatrial conduction, assessed by P-wave duration, is prolonged compared with age-matched control subjects.
      • Steinbigler P.
      • Haberl R.
      • König B.
      • Steinbeck G.
      P-Wave signal averaging identifies patients prone to alcohol-induced paroxysmal atrial fibrillation.
      Of note however, P-wave duration was also prolonged in control subjects with no history of AF after the intake of 1.5 g/kg ethanol. This may point toward immediate alcohol-related effects on slowing interatrial conduction independently from previous alcohol-consuming history. Furthermore, tissue Doppler echocardiography confirmed an interatrial electromechanical delay after alcohol consumption.
      • Sengul C.
      • Cevik C.
      • Ozveren O.
      • et al.
      Acute alcohol consumption is associated with increased interatrial electromechanical delay in healthy men.
      To date, electrophysiologic changes during washout, hangover periods, or AWS have not been well characterised. In AWS, however, beta-adrenergic discharge from the brain stem is suspected to increase arrhythmia risk, but detailed insights remain scarce.
      • Voskoboinik A.
      • Prabhu S.
      • Ling L.H.
      • Kalman J.M.
      • Kistler P.M.
      Alcohol and atrial fibrillation: a sobering review.

      Atrial cardiomyopathy due to chronic alcohol consumption

      Chronic alcohol consumption is associated with atrial cardiomyopathy, reflecting both structural and functional remodelling. After 2 months of alcohol consumption, rats demonstrated a decreased myofilament calcium sensitivity and an altered responsiveness to inotropes.
      • Piano M.R.
      • Rosenblum C.
      • Solaro R.J.
      • Schwertz D.
      Calcium sensitivity and the effect of the calcium sensitising drug pimobendan in the alcoholic isolated rat atrium.
      After 6 month of consumption, atrial conduction slowed, atrial refractoriness shortened, dispersion of refractoriness increased, and conduction velocity decreased in both atria of the rats. Conduction slowing, in combination with shortening of atrial refractoriness, shortens wavelength and facilitates reentry, which was associated with increased AF inducibility.
      • Zhang H.
      • Ruan H.
      • Rahmutula D.
      • et al.
      Effect of acute and chronic ethanol on atrial fibrillation vulnerability in rats.
      These results were confirmed in human studies, where patients with AF had significantly shorter atrial effective refractory periods and where electroanatomic mapping revealed lower bipolar global voltages, complex atrial potentials, and slow atrial conduction velocity in drinkers compared with nondrinkers.
      • Voskoboinik A.
      • Wong G.
      • Lee G.
      • et al.
      Moderate alcohol consumption is associated with atrial electrical and structural changes: Insights from high-density left atrial electroanatomic mapping.
      In addition, every consumed standard drink increased the probability of low-voltage regions by 10% in a population undergoing pulmonary vein isolation.
      • Qiao Y.
      • Shi R.
      • Hou B.
      • et al.
      Impact of alcohol consumption on substrate remodelling and ablation outcome of paroxysmal atrial fibrillation.
      Ultrastructural changes were demonstrated in dogs consuming alcohol for more than 1 year. Those changes included localised dilation and cystic changes in intercalated discs, which may disturb cell-cell impulse propagation.
      • Ettinger P.O.
      • Lyons M.
      • Oldewurtel H.A.
      • Regan T.J.
      Cardiac conduction abnormalities produced by chronic alcoholism.
      In humans, alcohol consumption is associated with atrial mechanical dysfunction,
      • Voskoboinik A.
      • Costello B.T.
      • Kalman E.
      • et al.
      Regular alcohol consumption is associated with impaired atrial mechanical function in the atrial fibrillation population: a cross-sectional MRI-based study.
      ,
      • Voskoboinik A.
      • Costello B.T.
      • la Gerche A.
      • et al.
      Relation of alcohol consumption to left ventricular fibrosis using cardiac magnetic resonance imaging.
      and alcohol is a predictor of an enlarged LA diameter and incident AF.
      • Mcmanus D.D.
      • Yin X.
      • Gladstone R.
      • et al.
      Alcohol consumption, left atrial diameter, and atrial fibrillation.
      ,
      • Singh K.J.
      • Cohen B.E.
      • Na B.
      • et al.
      Alcohol consumption and 5-year change in left atrial volume among patients with coronary heart disease: results from the Heart and Soul Study.
      Cardiac magnetic resonance imaging in healthy binge drinkers could furthermore shed light on underlying structural changes, because transient increases in ventricular T2-signal intensity were indicative of myocardial edema and global relative enhancement consistent with hyperemia.
      • Zagrosek A.
      • Messroghli D.
      • Schulz O.
      • Dietz R.
      • Schulz-Menger J.
      Effect of binge drinking on the heart as assessed by cardiac magnetic resonance imaging.
      However it is not known if the atria are equally affected in binge drinkers or after a single binge-drinking episode.

      Autonomic effects of alcohol

      Alcohol consumption is associated with an autonomic activation, resembling both sympathetic and vagal responses. Generally, vagal activation shortens atrial refractoriness and may facilitate reentry, whereas sympathetic activation increases cellular calcium concentrations, which in combination with spontaneous calcium releases from the sarcoplasmic reticulum may result in AF triggers. Moreover, AF itself may be triggered by simultaneous discharge of both sympathetic and parasympathetic nervous system.
      • Linz D.
      • Elliott A.D.
      • Hohl M.
      • et al.
      Role of autonomic nervous system in atrial fibrillation.
      Voskoboinik et al.,
      • Voskoboinik A.
      • McDonald C.
      • Chieng D.
      • et al.
      Acute electrical, autonomic and structural effects of binge drinking: Insights into the “holiday heart syndrome.
      Weise et al.,
      • Weise F.
      • Krell D.
      • Brinkhoff N.
      Acute alcohol ingestion reduces heart rate variability.
      and Brunner et al.
      • Brunner S.
      • Winter R.
      • Werzer C.
      • et al.
      Impact of acute ethanol intake on cardiac autonomic regulation.
      demonstrated a complex autonomic response to alcohol consumption. Whereas the consumption phase as such was associated with an increase in sympathetic activity, demonstrated in a decrease in heart rate variability (HRV), the hangover period was marked by a rebound phase. During the rebound phase, atrial ectopic counts increased, HRV remained reduced, and heart rate slowed down pronouncedly.
      • Voskoboinik A.
      • McDonald C.
      • Chieng D.
      • et al.
      Acute electrical, autonomic and structural effects of binge drinking: Insights into the “holiday heart syndrome.
      • Weise F.
      • Krell D.
      • Brinkhoff N.
      Acute alcohol ingestion reduces heart rate variability.
      • Brunner S.
      • Winter R.
      • Werzer C.
      • et al.
      Impact of acute ethanol intake on cardiac autonomic regulation.
      The Munich BREW study also demonstrated a reduction in sinus rhythm arrhythmia, generally resembling impaired autonomic function.
      • Brunner S.
      • Herbel R.
      • Drobesch C.
      • et al.
      Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich Octoberfest: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW).
      Furthermore, vagally dominated periods, such as rest, sleep, and eating, may be relevant inciters of paroxysmal AF episodes associated to alcohol intake.
      • Mandyam M.C.
      • Vedantham V.
      • Scheinman M.M.
      • et al.
      Alcohol and vagal tone as triggers for paroxysmal atrial fibrillation.
      Sympathetic responses to alcohol were also investigated in patients with previous alcohol-induced AF. Lymphocyte B-receptor density in the blood increased in response to 1.25 g/kg alcohol.
      • Mäki T.
      • Toivonen L.
      • Koskinen P.
      • et al.
      Effect of ethanol drinking, hangover, and exercise on adrenergic activity and heart rate variability in patients with a history of alcohol-induced atrial fibrillation.
      Interestingly, pressor responses to acute alcohol consumption were potentiated in hypertensive patients compared with normotensive control subjects, which may contribute to both alcohol-related blood pressure increases and other cardiovascular responses, including AF, in hypertensive patients.
      • Hering D.
      • Kucharska W.
      • Kara T.
      • Somers V.K.
      • Narkiewicz K.
      Potentiated sympathetic and hemodynamic responses to alcohol in hypertensive vs normotensive individuals.
      This indicates an important relevance of alcohol consumption for AF-associated comorbidities.

      Alcohol consumption and AF-associated comorbidities

      AF is often the consequence of atrial cardiomyopathy potentially formed by a wide range of AF-associated comorbidities and risk factors.
      • Heijman J.
      • Linz D.
      • Schotten U.
      Dynamics of atrial fibrillation mechanisms and comorbidities.
      Alcohol consumption is pathophysiologically linked with AF risk factors such as hypertension, sleep apnea, and left ventricular dysfunction, which can perpetuate an AF substrate.
      • Voskoboinik A.
      • Marcus G.M.
      The impact of alcohol intake on atrial fibrillation.
      In a meta-analysis, patients with regular alcohol consumption could significantly reduce blood pressure and manage their coexisting hypertension as they restricted their daily alcohol intake.
      • Roerecke M.
      • Kaczorowski J.
      • Tobe S.W.
      • et al.
      The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis.
      Vice versa, as mentioned above, alcohol consumption is associated with potentiated pressor responses in hypertension, which indicates that similar pathophysiologic pathways are affected by alcohol intake and hypertension. Alcohol is moreover associated with disturbed sleep and sleep-disordered breathing. Alcohol consumption was found to disturb general sleep architecture, which might be related to AF risk.
      • Christensen M.A.
      • Dixit S.
      • Dewland T.A.
      • et al.
      Sleep characteristics that predict atrial fibrillation.
      • Genuardi M.v.
      • Ogilvie R.P.
      • Saand A.R.
      • et al.
      Association of short sleep duration and atrial fibrillation.
      • Mehra R.
      • Marcus G.M.
      Novel insights into sleep disorder and atrial fibrillation risk: more than sleep apnea.
      In observational studies, sedative effects of alcohol could increase the sleep apnea severity score, apnea/hypopnea index,
      • Scanlan M.F.
      • Roebuck T.
      • Little P.J.
      • Redman J.R.
      • Naughton M.T.
      Effect of moderate alcohol upon obstructive sleep apnoea.
      which is an important contributor to acute and chronic AF risk.
      • Linz D.
      • Brooks A.G.
      • Elliott A.D.
      • et al.
      Variability of sleep apnea severity and risk of atrial fibrillation: the VARIOSA-AF Study.
      • Linz D.
      • Schotten U.
      • Neuberger H.R.
      • Böhm M.
      • Wirth K.
      Negative tracheal pressure during obstructive respiratory events promotes atrial fibrillation by vagal activation.
      • Linz D.
      • Linz B.
      • Hohl M.
      • Böhm M.
      Atrial arrhythmogenesis in obstructive sleep apnea: therapeutic implications.
      One potential pathophysiologic link between alcohol consumption, OSA, and increased AF risk might provide the activation of the proarrhythmic protein calmodulin kinase II (CaMKII). In rabbits and Langendorff-perfused human atrial preparations, CaMKII was increased after binge drinking exposure. Interestingly, CaMKII has recently been reported to be associated with 3 cardinal pathophysiologic aspects of OSA: thoracic pressure changes, asphyxia, and oxidative stress.
      • Toischer K.
      • Rokita A.G.
      • Unsöld B.
      • et al.
      Differential cardiac remodelling in preload versus afterload.
      • Wagner S.
      • Ruff H.M.
      • Weber S.L.
      • et al.
      Reactive oxygen species–activated Ca/calmodulin kinase IIδ is required for late INa augmentation leading to cellular Na and Ca overload.
      • Dybkova N.
      • Wagner S.
      • Backs J.
      • et al.
      Tubulin polymerization disrupts cardiac β-adrenergic regulation of late INa.
      Therefore, after an evening of binge drinking, as alcohol directly induces pathways for increased CaMKII
      • Mustroph J.
      • Lebek S.
      • Maier L.S.
      • Neef S.
      Mechanisms of cardiac ethanol toxicity and novel treatment options.
      it might also increase the likelihood and frequency of apneic events, which again act on CaMKII and might perpetuate its activity.
      Although alcohol increases arrhythmia risk in otherwise healthy individuals, preexisting atrial structural alterations are suspected to have a worsening impact on arrhythmogenesis,
      • Thornton J.R.
      Atrial fibrillation in healthy nonalcoholic people after an alcoholic binge.
      ,
      • Sengul C.
      • Cevik C.
      • Ozveren O.
      • et al.
      Acute alcohol consumption is associated with increased interatrial electromechanical delay in healthy men.
      which becomes important as chronic alcohol intake induces structural remodelling.
      • Fernández-Solà J.
      The effects of ethanol on the heart: alcoholic cardiomyopathy.
      An in silico modulation of alcohol-induced arrhythmic effects demonstrated differential proarrhythmic effects of alcohol exposure dependent on the underlying structural substrate. Of note, low concentrations were associated with atrial action potential prolongation, providing an explanation for a potential J-shaped risk association with increasing concentrations of alcohol intake.
      • Sutanto H.
      • Cluitmans M.J.M.
      • Dobrev D.
      • et al.
      Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: insights from multiscale in silico analyses.
      Moreover, some studies point toward a beneficial effect of moderate alcohol consumption for the general development of certain cardiovascular diseases and cardiovascular outcomes.
      • Sutanto H.
      • Cluitmans M.J.M.
      • Dobrev D.
      • et al.
      Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: insights from multiscale in silico analyses.
      • Bell S.
      • Daskalopoulou M.
      • Rapsomaniki E.
      • et al.
      Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records.
      • Gardner J.D.
      • Mouton A.J.
      Alcohol effects on cardiac function.
      However, the precise investigation of the extent of alcohol consumption and its consequences for cardiovascular diseases being associated with AF remains challenging owing to insufficient adjustment for confounding variables in available clinical cohort studies.
      • Bell S.
      • Daskalopoulou M.
      • Rapsomaniki E.
      • et al.
      Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records.
      Overall, the J-shaped associations between alcohol and other cardiovascular outcomes have not been shown for alcohol and AF, suggesting a rather linear relationship without any threshold of alcohol consumption below which AF risk is not increased.
      • Larsson S.C.
      • Drca N.
      • Wolk A.
      Alcohol consumption and risk of atrial fibrillation a prospective study and dose-response meta-analysis.
      ,
      • Kodama S.
      • Saito K.
      • Tanaka S.
      • et al.
      Alcohol consumption and risk of atrial fibrillation: a meta-analysis.
      ,
      • Cha M.J.
      • Oh G.C.
      • Lee H.
      • et al.
      Alcohol consumption and risk of atrial fibrillation in asymptomatic healthy adults.

      Conclusion and Therapeutic Implications

      Alcohol consumption is an accepted and popular lifestyle component, but binge drinking as well as habitual drinking at moderate levels are associated with increased AF risk by direct effects transiently increasing AF risk (holiday heart syndrome) and progressive development of an arrhythmogenic substrate.
      Although subject to potential confounding error, results from epidemiologic studies draw a rather consistent picture that alcohol abstinence is beneficial for AF recurrence and treatment and for the prevention or development of AF-associated comorbidities. As the relation of alcohol consumption and AF risk seems to be rather linear, a safe level of daily alcohol intake in patients with a history of AF may not exist. However, further studies are warranted to support evidence for the best clinical recommendations.

      Funding Sources

      The authors have no funding sources to declare.

      Disclosures

      The authors have no conflicts of interest to disclose.

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