Association betweenALDH2genotypes and atrial fibrillation recurrence following catheter ablation: prospective multicenter cohort study

Background Alcohol, a risk factor for atrial fibrillation (AF), is metabolized by aldehyde dehydrogenase 2 (ALDH2). Notably, alcohol flushing syndrome attributed to the dysfunctional alleles of ALDH2 (ALDH2-deficient variant) carriers are prevalent among East Asian populations. These patients are at risk for developing AF when accompanied with habitual alcohol consumption. However, the effect of the ALDH2 genotype on catheter ablation, the most successful treatment option for AF, remains unclear.

Totally 371 patients who underwent their first catheter ablation for AF were enrolled in this prospective cohort study. They were categorized into four groups based on their ALDH2 genotypes and habitual alcohol consumption to understand the contribution status to their impact on the risk of AF recurrence. The primary outcome was to determine the proportion of AF recurrence among the four groups during a 1-year follow-up period using Kaplan–Meier analysis. The secondary outcome involved assessing the contributions of each group to AF recurrence and other risk factors using multivariate analysis.

This study comprised 239 ALDH2-wild type (147 habitual drinkers) and 132 ALDH2-deficient variant carriers (31 habitual drinkers). Kaplan–Meier curves indicated that ALDH2-deficient variant carriers with habitual alcohol consumption exhibited the highest proportion of AF recurrence compared with the other groups (p<0.01). In addition, ALDH2-deficient variant itself was not associated with AF recurrence (hazard ratio [HR]=1.56, p=0.10), ALDH2-deficient variant carriers with habitual alcohol consumption exhibited a higher HR (HR=5.01, p=0.02) in multivariate analysis. Notably, it conferred a higher risk than that for ALDH2 wild-type patients with habitual alcohol consumption (HR=2.36, p=0.02).

While the ALDH2-deficient variant itself showed no correlation with AF recurrence, it emerged as a significant risk factor for AF when accompanied with habitual alcohol consumption. Thus, abstinence from alcohol may be necessary, even after catheter ablation is performed, especially for patients with the ALDH2-deficient variant. What is Known? Alcohol, a risk factor for atrial fibrillation (AF), is metabolized by aldehyde dehydrogenase 2 (ALDH2); notably, alcohol flushing syndrome owing to dysfunctional alleles of ALDH2 (ALDH2-deficient variant) is prevalent among East Asians. However, the relationship between ALDH2 genotypes and AF recurrence following catheter ablation has not been clarified yet. What the Study Adds While the ALDH2-deficient variant itself was not associated with AF recurrence, it emerged as a major risk factor for AF recurrence when accompanied with habitual alcohol consumption. Abstinence from alcohol consumption may be necessary, even after catheter ablation, especially for ALDH2-deficient variant carriers. Competing Interest Statement Dr Tsujita has received honoraria from AMI Co., Ltd., Bayer Yakuhin, Ltd., Bristol-Myers K.K., EA Pharma Co.,Ltd., MOCHIDA PHARMACEUTICAL CO., LTD., and scholarship fund from AMI Co., Ltd., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Edwards Lifesciences Corporation, Johnson & Johnson K.K., ONO PHARMACEUTICAL CO., LTD., Otsuka Pharmaceutical Co.,Ltd., Takeda Pharmaceutical Co., Ltd., and honoraria from Amgen K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co. Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co.,Ltd., Pfizer Japan Inc., and belongs to the endowed departments donated by Abbott Japan Co., Ltd., Boston Scientific Japan K.K., Fides-one, Inc., GM Medical Co., Ltd., ITI Co.,Ltd., Kaneka Medix Co., Ltd., NIPRO CORPORATION, TERUMO Co, Ltd., Abbott Medical Co., Ltd., Cardinal Health Japan, Fukuda Denshi Co., Ltd., Japan Lifeline Co.,Ltd., Medical Appliance Co., Ltd., Medtoronic Japan Co., Ltd. Clinical Trial This investigation was not an interventional study, but cohort study. Funding Statement This work was supported by JPSS KAKENHI (Grant number JP20K22878) and Takeda Science Foundation Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Human Research Committee of Kumamoto University Hospital, Miyazaki Medical Association Hospital, and Kumamoto Chuo Hospital (ethical approval number; genome 466). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability The datasets used and analyzed during the current study available from the corresponding author on reasonable request. Non-standard Abbreviations and Acronyms - ALDH2 - Aldehyde dehydrogenase 2 - AAD - Antiarrhythmic drug - AF - Atrial fibrillation - CI - Confidence interval - HR - Hazard ratio - PV - Pulmonary vein