ALDH2 gene polymorphisms and metabolite alterations in the recurrence of atrial fibrillation after radiofrequency catheter ablations: a prospective and multicenter study

Background The association between acetaldehyde dehydrogenase 2 (ALDH2) polymorphisms and atrial fibrillation (AF) remains controversial. Objectives To investigate whether ALDH2 polymorphisms were associated with AF recurrence after radiofrequency catheter ablation (RFCA), including changes in underlying metabolites. Methods A total of 309 patients with new-onset AF, scheduled for follow-up in three medical centers, were prospectively enrolled. Patients were categorized into three groups based on ALDH2 genotypes. Multiple Cox regression models were used to identify predictors of AF recurrence after RFCA. 27 plasma samples were collected from patients before RFCA procedures to examine differential metabolites and metabolic pathways among ALDH2 polymorphisms. Results There were 69 (22.33%) cases of AF recurrence after RFCA during a median follow-up of 10.63 months [interquartile range: 4.57-12.00]. Kaplan-Meier analysis showed that patients with ALDH2-AA genotype had the highest recurrence rate (Log rank P=0.031). The ALDH2-AA genotype was the independent predictor of AF recurrence from multivariable Cox regression analysis by adjusting for different risk factors (adjusted HR: 2.43, [95% CI, 1.10-5.36], p=0.028). 16 metabolites in plasma samples were found to reflect metabolic differences from patients undergoing RFCA procedures among ALDH2 polymorphisms (variable importance in projection ≥ 1, P ≤ 0.05). ALDH2-AA genotype experienced the highest levels of L-Glutamine. Conclusion ALDH2-AA genotype was significantly associated AF recurrence after RFCA. The addition of ALDH2 genotypes into conventional risk factors significantly improves the ability to predict risk of AF recurrence after RFCA. L-Glutamine might be the main metabolite that distinguishes patients with the ALDH2-AA genotype.