AIM To investigate the mechanism of recurrence of atrial fibrillation (AF) after radiofrequency ablation based on weighted gene co-expression network analysis (WGCNA) method.

METHODS Differential genes of AF and sinus rhythm in GSE2240, GSE41177 and GSE115574 were analyzed by limma method and WGCNA was used to identify the gene module with the strongest AF association. Dehydrogenase/reductase (DHRS) 9 was enriched by GeneMANIN website and KEGG software. A total of 102 patients with atrial fibrillation admitted to the Cardiovascular Department of Zhangjiakou First Hospital from June, 2021 to November, 2022 and undergoing their first radiofrequency ablation in our hospital were selected as study subjects. The patients were divided into the control group (using amiodarone alone) and research group (using sarcubactril valsartan and amiodarone) according to the drugs administrated. The primary endpoint was AF recurrence and the secondary endpoint was cardiac structural indexes and DHRS9 levels. At 1 year follow-up, they were divided by DHRS9 into high and low expression groups according to the cutoff value (8.17) of ROC curve. Different statistical methods were used to analyze the impact on AF recurrence in the research group and the control group as well as in the groups of high and low expressions of DHRS9.

RESULTS The crossover gene of WGCNA and limma methods was DHRS9, which was mainly concentrated in regulating innate immune response and various metabolic pathways. At the end of the follow-up, no recurrence of AF occurred in 64 cases (62.8%) and the survival analysis showed that the rate of AF recurrence in the research group was significantly higher than that in the control group (71.15% vs. 54.00%, P<0.05). ROC curve results suggested that the area under curve of DHRS9 for predicting AF recurrence was 86.0% (P<0.01). There was a statistically significant difference in the non-recurrence rate of AF with high and low expressions of DHRS9 (88.2% vs. 11.8%, P<0.01), COX univariate suggested that the probability of AF recurrence in patients with high expression of DHRS9 might be 18.05 times higher than that in patients with low expression of DHRS9. In patients with recurrent AF, compared with the control group, the study group had N-terminal B-type natriuretic peptide precursor levels (P<0.01), left atrial diameter (P<0.05), and left ventricular diameter (P<0.05) The level of DHRS9 (P<0.01) significantly decreased, while the left ventricular ejection fraction significantly increased, with a statistically significant difference (P<0.05). CONCLUSION Sacubactril valsartan combined with amiodarone is beneficial for the prevention of AF recurrence, which is associated with decreased DHRS9 expression. High level of DHRS9 may be the molecular manifestation of the atrial remodeling during AF recurrence.