Background

To which extent atrial remodeling occurs before atrial fibrillation (AF) is unknown.

Objective

The PREventive left atrial appenDage resection for the predICtion of fuTure Atrial Fibrillation (PREDICT-AF) study investigated such subclinical remodeling, which may be used for risk stratification and AF prevention.

Methods

Patients (N = 150) without a history of AF with a CHA₂DS₂-VASc score of ≥2 at an increased risk of developing AF were included. The left atrial appendage was excised and blood samples were collected during elective cardiothoracic surgery for biomarker discovery. Participants were followed for 2 years with Holter monitoring to determine any atrial tachyarrhythmia after a 50-day blanking period.

Results

Eighteen patients (12%) developed incident AF, which was associated with increased tissue gene expression of collagen I (COL1A1), collagen III (COL3A1), and collagen VIII (COL8A2), tenascin-C (TNC), thrombospondin-2 (THBS2), and biglycan (BGN). Furthermore, the fibroblast activating endothelin-1 (EDN1) and sodium voltage-gated channel β subunit 2 (SCN2B) were associated with incident AF whereas the Kir2.1 channel (KCNJ2) tended to downregulate. The plasma levels of COL8A2 and TNC correlated with tissue expression and predicted incident AF. A gene panel including tissue KCNJ2, COL1A1, COL8A2, and EDN1 outperformed clinical prediction models in discriminating incident AF.

Conclusion

The PREDICT-AF study demonstrates that atrial remodeling occurs long before incident AF and implies future potential for early patient identification and therapies to prevent AF (ClinicalTrials.gov identifier NCT03130985).

中文翻译：

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房颤之前的细胞外基质重塑：PREDICT-AF 试验的结果

背景

心房重构在心房颤动 (AF) 之前发生的程度尚不清楚。

客观的

PREventive 左心耳切除术预测未来心房颤动 (PREDICT-AF) 研究调查了这种亚临床重塑，可用于风险分层和 AF 预防。

方法

_{纳入无房颤病史且 CHA 2} DS ₂ -VASc 评分≥2 且发生房颤风险增加的患者（N = 150） 。在择期心胸手术期间切除左心耳并收集血液样本以发现生物标志物。在 50 天的空白期后，参与者通过动态心电图监测跟踪了 2 年以确定任何房性快速心律失常。

结果

18 名患者 (12%) 发生房颤，这与胶原蛋白 I ( COL1A1 )、胶原蛋白 III ( COL3A1 ) 和胶原蛋白 VIII ( COL8A2 )、肌腱蛋白-C ( TNC )、血小板反应蛋白-2 ( THBS2 ) 的组织基因表达增加有关) 和双糖链蛋白聚糖 ( BGN )。此外，成纤维细胞激活 endothelin-1 ( EDN1 ) 和钠电压门控通道 β 亚基 2 ( SCN2B ) 与发生 AF 相关，而 Kir2.1 通道 ( KCNJ2 ) 倾向于下调。COL8A2 和 TNC 的血浆水平与组织表达相关并预测发生 AF。包括组织KCNJ2的基因组，COL1A1、COL8A2和EDN1在区分事件 AF 方面的表现优于临床预测模型。

结论

PREDICT-AF 研究表明，心房重构早在发生 AF 之前就发生了，这意味着未来有可能进行早期患者识别和治疗以预防 AF（ClinicalTrials.gov 标识符 NCT03130985）。