Association of atrial fibrillation burden and clinical profile with blood biomarkers: Results from the ISOLATION Ablation Cohort

IF 2.5 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart Rhythm O2 Pub Date : 2025-05-01 DOI:10.1016/j.hroo.2025.02.017

Zarina Habibi MD , Dominique V.M. Verhaert MD, PhD , Konstanze Betz MD , Ben J.M. Hermans MD, PhD , Joris Winters MD, PhD , Suzanne A.M. Philippens , Sevasti-Maria Chaldoupi MD, PhD , Bart Maesen MD, PhD , Jos G. Maessen MD, PhD , Aaron Isaacs PhD , Sjoerd W. Westra MD , Robin Nijveldt MD, PhD , Ludovic Gillet PhD , Ursula-Henrike Wienhues-Thelen PhD , Merlin Koehler , Stef Zeemering PhD , Kevin Vernooy MD, PhD , Dominik Linz MD, PhD , Ulrich Schotten MD, PhD

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Abstract

Background

Advances have been made in identifying biomarkers for atrial fibrillation (AF) outcomes.

Objective

The link between clinical determinants, especially AF burden, and blood biomarkers remains underexplored.

Methods

We conducted a cross-sectional analysis of AF patients scheduled for catheter ablation in the ISOLATION study (July 2020–May 2022, NCT04342312). Patient characteristics and blood samples were collected before ablation. AF burden was assessed using hand-held electrocardiograms (ECGs) over 4 weeks. Blood samples were analyzed for biomarkers, including bone morphogenetic protein 10 (BMP10), angiopoietin-2 (Ang-2), fibroblast growth factor 23 (FGF23), and others. We trained elastic net regression models to identify the most important clinical determinants out of 64 available clinical features.

Results

We analyzed blood samples from 508 patients with a mean age of 63 ±9 years; 31.1% were female. Of these, 70% had paroxysmal AF and 30% persistent AF. Heart failure was present in 15% of patients. In 140 patients (28%), AF was observed during blood draw. AF burden before ablation was available in 389 patients. After multivariable analysis, the following clinical determinants were independently associated with biomarker levels: AF burden, AF during blood draw, age, heart failure, decreased kidney function, and female sex. Most notably, AF burden and AF rhythm at the time of sampling were strongly associated with various biomarker levels. Female sex was positively associated with BMP10 and FGF23, but negatively associated with high sensitive Troponin-T (hs-TNT).

Conclusions

AF burden is a strong determinant of many biomarkers, underpinning their relevance as covariates in biomarker studies. Pro-fibrotic biomarkers are increased in female patients, whereas male patients more often show elevated biomarkers of myocardial injury.

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房颤负担和临床特征与血液生物标志物的关联：来自隔离消融队列的结果

背景在鉴定心房颤动（AF）预后的生物标志物方面取得了进展。目的临床决定因素，特别是心房颤动负担与血液生物标志物之间的联系仍未得到充分探讨。方法：我们在ISOLATION研究（2020年7月- 2022年5月，NCT04342312）中对计划进行导管消融的房颤患者进行了横断面分析。消融前采集患者特征及血液样本。4周内使用手持心电图（ECGs）评估心房颤动负荷。对血液样本进行生物标志物分析，包括骨形态发生蛋白10 （BMP10）、血管生成素-2 （Ang-2）、成纤维细胞生长因子23 （FGF23）等。我们训练弹性网络回归模型来识别64个可用临床特征中最重要的临床决定因素。结果我们分析了508例患者的血液样本，平均年龄为63±9岁；31.1%为女性。其中，70%为阵发性房颤，30%为持续性房颤。15%的患者存在心力衰竭。140例（28%）患者在抽血时出现房颤。389例患者消融前房颤负荷。多变量分析后，以下临床决定因素与生物标志物水平独立相关：房颤负担、抽血时房颤、年龄、心力衰竭、肾功能下降和女性性别。最值得注意的是，采样时心房颤动负荷和心房颤动节律与各种生物标志物水平密切相关。女性与BMP10和FGF23呈正相关，但与高敏感肌钙蛋白- t （hs-TNT）呈负相关。结论：saf负担是许多生物标志物的重要决定因素，支持其在生物标志物研究中作为协变量的相关性。促纤维化生物标志物在女性患者中升高，而男性患者更常表现为心肌损伤生物标志物升高。

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