Liu Tong, Zhou Dong-Tao, Liu Fang, Long De-Yong, Yang Yang, Li Meng-Meng, Zhao Xin, Li Chang-Yi, Wang Wei, Jiang Chen-Xi, Tang Ri-Bo
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
Heart Rhythm O2. 2025 Feb 7;6(5):622-630. doi: 10.1016/j.hroo.2025.02.001. eCollection 2025 May.
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.
This study aimed to evaluate the predictive value of GPX4 for AF recurrence after ablation and the relationship between atrial fibrosis and ferroptosis.
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.
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.
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.
心房纤维化介导心房颤动（AF）的发生和维持。谷胱甘肽过氧化物酶4（GPX4）是一种铁死亡生物标志物。关于AF中的铁死亡或GPX4与心房纤维化之间的关系知之甚少。
本研究旨在评估GPX4对消融术后AF复发的预测价值以及心房纤维化与铁死亡之间的关系。
本研究纳入了249例行消融术的AF患者。采用酶联免疫吸附测定法评估血清GPX4和转化生长因子β（TGFβ）水平。主要结局是随访12个月期间AF复发。
根据TGFβ三分位数，将249例患者分为3组。随着TGFβ升高，血清GPX4水平降低。随访12个月后，54例患者发生AF复发。多因素Cox回归分析显示，GPX4水平是AF复发的独立预测因素（风险比0.308）。在调整潜在混杂因素后，GPX4三分位数仍是AF复发的预测因素。相关性分析表明，GPX4与心房纤维化和左心房大小相关。受试者工作特征分析显示，AF复发的截断值为3740 pg/mL。此外，将GPX4纳入左心房维度指数和TGFβ模型可显著改善对AF复发风险的预测。
GPX4对AF复发显示出优异的预测价值，且与TGFβ呈负相关，表明铁死亡可能参与心房纤维化。该模型可为临床决策提供参考。
