TY - JOUR
T1 - Association of atrial fibrillation burden and clinical profile with blood biomarkers
T2 - Results from the ISOLATION Ablation Cohort
AU - Habibi, Zarina
AU - Verhaert, Dominique V.M.
AU - Betz, Konstanze
AU - Hermans, Ben J.M.
AU - Winters, Joris
AU - Philippens, Suzanne A.M.
AU - Chaldoupi, Sevasti Maria
AU - Maesen, Bart
AU - Maessen, Jos G.
AU - Isaacs, Aaron
AU - Westra, Sjoerd W.
AU - Nijveldt, Robin
AU - Gillet, Ludovic
AU - Wienhues-Thelen, Ursula Henrike
AU - Koehler, Merlin
AU - Zeemering, Stef
AU - Vernooy, Kevin
AU - Linz, Dominik
AU - Schotten, Ulrich
N1 - Funding Information:
On behalf of all the ISOLATION investigators. ISOLATION was supported by the Netherlands Heart Foundation (Grant number 01-002-2022-0118, EmbRACE: Electro-Molecular Basis and the theRapeutic management of Atrial Cardiomyopathy, fibrillation and associated outcomEs), the European Union (ITN Network Personalize AF: Personalized Therapies for Atrial Fibrillation: a translational network, grant number 860974; MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation, grant number 965286), and the Leducq Foundation (Immune Targets for the Treatment of Atrial Fibrillation). US received grants, consultancy fees or honoraria from Universit\u00E0 della Svizzera Italiana (USI, Switzerland), EP Solutions Inc. (Switzerland), Johnson & Johnson Medical Limited, (United Kingdom), Bayer Healthcare (Germany). US is co-founder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht. All authors attest they meet the current ICMJE criteria for authorship. Participants provided written informed consent for data collection and analysis. The study protocol was carried out in accordance with Declaration of Helsinki guidelines and was approved by the Institutional Review Board. The studies involving human participants were reviewed and approved by METC azM/UM. The patients/participants provided their written informed consent to participate in this study. METC azM/UM, NL70787.068.19
Funding Information:
ISOLATION was supported by the Netherlands Heart Foundation (Grant number 01-002-2022-0118, EmbRACE: Electro-Molecular Basis and the theRapeutic management of Atrial Cardiomyopathy, fibrillation and associated outcomEs), the European Union (ITN Network Personalize AF: Personalized Therapies for Atrial Fibrillation: a translational network, grant number 860974; MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation, grant number 965286), and the Leducq Foundation (Immune Targets for the Treatment of Atrial Fibrillation).
Publisher Copyright:
© 2025 Heart Rhythm Society
PY - 2025/1/1
Y1 - 2025/1/1
N2 - 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.
AB - 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.
KW - Atrial fibrillation
KW - Biomarkers
KW - BMP10
KW - Burden
KW - Catheter ablation
KW - Preprocedural atrial fibrillation
KW - Sex differences
U2 - 10.1016/j.hroo.2025.02.017
DO - 10.1016/j.hroo.2025.02.017
M3 - Article
SN - 2666-5018
JO - Heart Rhythm O2
JF - Heart Rhythm O2
ER -