Alcohol Abstinence in Drinkers with Atrial Fibrillation

Voskoboinik, Aleksandr; Kalman, Jonathan M.; Silva, Anurika P De; Nicholls, Thomas; Costello, B.; Nanayakkara, Shane; Prabhu, Sandeep; Stub, Dion; Azzopardi, Sonia; Vizi, Donna; Wong, G.; Nalliah, C.; Sugumar, Hariharan; Wong, Maria M.; Kotschet, Emily; Kaye, David M.; Taylor, Andrew J.; Kistler, Peter M.

doi:10.1056/nejmoa1817591

Cited by 323 publications

(200 citation statements)

References 26 publications

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“…A previous meta-analysis reported an 8% increase in the risk of AF for each 10 g/day increase in alcohol consumption or per drink and day [21]. In addition, a recent randomized and controlled trial showed a lower recurrence and burden of AF among patients who reduced their alcohol consumption than among matched controls at 6 months of follow-up [27]. However, the mechanisms underlying the association between alcohol consumption and the development and perpetuation of AF remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE

Hsu

Tsai

Yeh

et al. 2020

IJMS

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Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts such as 4-hydroxy-trans-2-nonenal (4-HNE). Previous meta-analyses have shown an increase in the risk of atrial fibrillation (AF) in patients with chronic alcohol consumption. ALDH2*2, a common dysfunctional polymorphism in the ALDH2 gene, has been linked to an increased risk of cancer and heart disease. We tested the effect of ALDH2 deficiency on alcohol-induced AF in a murine model of chronic-binge ethanol feeding, with ALDH2*2 knock-in (KI) mice generated by a CRISPR/CAS9 system. In addition, right atrial appendages were obtained from eight patients with AF undergoing open heart surgery. The results showed that burst atrial pacing induced a greater susceptibility to AF in ALDH2*2 KI mice exposed to chronic ethanol intoxication than in wild-type mice, resulting from a higher degree of 4-HNE accumulation and collagen deposition in their atria. Alda-1 attenuated transforming growth factor beta 1 (TGF-β1) expression and collagen deposition in the atria and reduced AF inducibility. Patients with AF and the ALDH2*2 allele exhibited greater oxidative stress and substrate remodeling in their atria than non-carriers. In conclusion, ALDH2 deficiency may increase the risk of chronic alcohol and tachypacing-induced AF through the accumulation of 4-HNE and increased ROS production.

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Section: Discussionmentioning

confidence: 99%

Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE

Hsu

Tsai

Yeh

et al. 2020

IJMS

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“…The detrimental effects of acute excessive ethanol consumption have been described in many studies [1,5,6,15,41]. Ethanol alters cardiac cellular electrophysiology, acutely slowing the conduction velocity [7,30].…”

Section: The Detrimental Effects Of High Ethanol Concentrationsmentioning

confidence: 99%

Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses

Sutanto

Cluitmans

Dobrev

et al. 2020

Journal of Molecular and Cellular Cardiology

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Acute excessive ethyl alcohol (ethanol) consumption alters cardiac electrophysiology and can evoke cardiac arrhythmias, e.g., in 'holiday heart syndrome'. Ethanol acutely modulates numerous targets in cardiomyocytes, including ion channels, Ca 2+-handling proteins and gap junctions. However, the mechanisms underlying ethanol-induced arrhythmogenesis remain incompletely understood and difficult to study experimentally due to the multiple electrophysiological targets involved and their potential interactions with preexisting electrophysiological or structural substrates. Here, we employed cellular-and tissue-level in-silico analyses to characterize the acute effects of ethanol on cardiac electrophysiology and arrhythmogenesis. Acute electrophysiological effects of ethanol were incorporated into human atrial and ventricular cardiomyocyte computer models: reduced I Na , I Ca,L , I to , I Kr and I Kur , dual effects on I K1 and I K,ACh (inhibition at low and augmentation at high concentrations), and increased I NCX and SR Ca 2+ leak. Multiscale simulations in the absence or presence of preexistent atrial fibrillation or heart-failure-related remodeling demonstrated that low ethanol concentrations prolonged atrial action-potential duration (APD) without effects on ventricular APD. Conversely, high ethanol concentrations abbreviated atrial APD and prolonged ventricular APD. High ethanol concentrations promoted reentry in tissue simulations, but the extent of reentry promotion was dependent on the presence of altered intercellular coupling, and the degree, type, and pattern of fibrosis. Taken together, these data provide novel mechanistic insight into the potential proarrhythmic interactions between a preexisting substrate and acute changes in cardiac electrophysiology. In particular, acute ethanol exposure has concentration-dependent electrophysiological effects that differ between atria and ventricles, and between healthy and diseased hearts. Low concentrations of ethanol can have anti-fibrillatory effects in atria, whereas high concentrations promote the inducibility and maintenance of reentrant atrial and ventricular arrhythmias, supporting a role for limiting alcohol intake as part of cardiac arrhythmia management.

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“…In humans, risk factor management has resulted in fewer recurrences of AF after ablation, and reversal of AF progression. 37,76,80 Patients with weight loss frequently regress from a persistent to paroxysmal phenotype and progress in the opposite direction much less frequently. 82…”

Section: Progression and Regression Of The Atrial Substratementioning

confidence: 99%

Atrial Fibrillation Structural Substrates: Aetiology, Identification and Implications

Al‐Kaisey

Lee

Kalman

2020

Arrhythm Electrophysiol Rev

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AF is the most common sustained cardiac rhythm disorder and is associated with increased morbidity and mortality. Since the first description of AF initiation by triggers from pulmonary veins sleeves, pulmonary vein isolation (PVI) has become the standard ablation strategy in patients with AF. 1 However, freedom from the arrhythmia, particularly in non-paroxysmal AF, remains suboptimal, and it is now clear that, in these patients, AF is maintained by an atrial substrate beyond the pulmonary veins. Although electrical remodelling may be reversible with termination of the arrhythmia, the development of atrial substrate due to fibrosis contributes to the progression of the AF phenotype from paroxysmal to persistent AF, leading to an arrhythmia that is more refractory to intervention. 2 It is clear from animal and human studies that prolonged AF can cause this structural change. Moreover, it is also apparent that a range of risk factors associated with AF, including age, obesity, heart failure (HF), valvular heart disease, hypertension (HT), sleep apnoea and alcohol intake, may also progress atrial remodelling. The rise in the prevalence of cardiovascular risk factors (particularly driven by ageing populations and the obesity epidemic) has been associated with an increase in the prevalence of AF and AF-related hospitalisations. 3 In this review, we focus on insights from electrophysiological mapping studies in cohorts with AF risk factors. We discuss substrate mapping and its implications for AF management and outcomes, and also focus on potential pitfalls. The Second Factor: Structural Remodelling is Required for AF Maintenance Early studies of animal models have demonstrated that AF promotes acute electrical remodelling, which in turn leads to further AF, thereby introducing the seminal concept that 'AF begets AF'. 4-6 In response to either induced AF or rapid atrial pacing, a reduction in the atrial effective refractory period (ERP) occurs with an increase in the spatial heterogeneity of ERP and loss of normal ERP rate adaptation, all resulting in progressively longer durations of AF. In this model, termination of the arrhythmia results in remodelling reversal, suggesting that sinus rhythm may beget sinus rhythm. However, human studies of early intervention to re-establish sinus rhythm do not fully support this concept; the re-establishment of sinus rhythm has not been found to prevent the progression of AF in the majority of patients. 7,8 Ongoing work has indicated that, beyond acute electrical remodelling, structural remodelling also occurs and is not necessarily fully reversible. This socalled second factor has been shown to occur as a result of longer durations of AF. However, the multiple conditions associated with AF also appear to promote significant structural remodelling.

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Alcohol Abstinence in Drinkers with Atrial Fibrillation

Cited by 323 publications

References 26 publications

Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE

Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE

Acute effects of alcohol on cardiac electrophysiology and arrhythmogenesis: Insights from multiscale in silico analyses

Atrial Fibrillation Structural Substrates: Aetiology, Identification and Implications

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