Glutathione peroxidase 4 as a potential biomarker for atrial fibrosis and recurrence of atrial fibrillation

Abstract

Background

Atrial fibrosis mediates the development and maintenance of atrial fibrillation (AF). Glutathione peroxidase 4 (GPX4) is a ferroptosis biomarker. Little is known about ferroptosis in AF or the relationship between GPX4 and atrial fibrosis.

Objective

This study aimed to evaluate the predictive value of GPX4 for AF recurrence after ablation and the relationship between atrial fibrosis and ferroptosis.

Methods

This study included 249 patients with AF who underwent ablation. The levels of serum GPX4 and transforming growth factor β (TGFβ) were evaluated by enzyme-linked immunosorbent assay. The primary outcome was AF recurrence during 12 months of follow-up.

Results

According to the tertiles of TGFβ, 249 patients were divided into 3 groups. With the increase of TGFβ, the serum level of GPX4 was decreased. After 12 months of follow-up, 54 patients experienced recurrence of AF. Multivariate Cox regression analysis revealed that the GPX4 level was an independent predictor of F recurrence (hazard ratio 0.308). After adjusting for potential confounding factors, the tertiles of GPX4 remained predictors of AF recurrence. Correlation analysis indicated that GPX4 was associated with atrial fibrosis and left atrial size. Receiver-operating characteristic analysis showed that the cutoff value for AF recurrence was 3740 pg/mL. Furthermore, incorporating GPX4 into the left atrial dimensional index and TGFβ model significantly improved the prediction of recurrent AF risk.

Conclusion

GPX4 showed excellent predictive value for AF recurrence and is negatively correlated with TGFβ, indicating that ferroptosis may be involved in atrial fibrosis. This model can serve as a reference for clinical decision making.