Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study

Winnie Chua; Alya Khashaba; Hansel Canagarajah; Jens Cosedis Nielsen; Luigi di Biase; Karl Georg Haeusler; Gerhard Hindricks; Lluis Mont; Jonathan Piccini; Renate B Schnabel; Ulrich Schotten; Ursula-Henrike Wienhues-Thelen; Tanja Zeller; Larissa Fabritz; Paulus Kirchhof

doi:10.1093/europace/euae028

Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study

Winnie Chua, Alya Khashaba, Hansel Canagarajah, Jens Cosedis Nielsen, Luigi di Biase, Karl Georg Haeusler, Gerhard Hindricks, Lluis Mont, Jonathan Piccini, Renate B Schnabel, Ulrich Schotten, Ursula-Henrike Wienhues-Thelen, Tanja Zeller, Larissa Fabritz, Paulus Kirchhof^*

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

Aims: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study.

Methods and results: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations.

Conclusion: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.

Original language	English
Article number	euae028
Number of pages	12
Journal	Europace
Volume	26
Issue number	2
Early online date	24 Jan 2024
DOIs	https://doi.org/10.1093/europace/euae028
Publication status	Published - Feb 2024

Bibliographical note

Funding:
AXAFA–AFNET5 received support from BMS/Pfizer and the German Centre for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK). The analyses reported here were supported in part by European Union-funded CATCH ME (grant agreement no. 633196) and MAESTRIA (grant agreement 965286), both to P.K., U.S., and L.F. Biomolecule quantification was performed by Roche Diagnostics as an in-kind donation to the CATCH ME project. J.C.N. was supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658) outside this work. U.-H.W.-T. is an employee of Roche Diagnostics.

Keywords

Ablation
Angiopoietin 2
Rhythm control
Bone morphogenetic protein 10
Atrial fibrillation
N-Terminal pro-B-type natriuretic peptide

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MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation
Kirchhof, P., Gkoutos, G. & Fabritz, L.
European Commission
1/03/21 → 28/02/26
Project: EU
H2020_COLLAB_CATCH ME_(LEAD)
Kirchhof, P., Fabritz, L., Hemming, K. & Deeks, J.
European Commission
1/05/15 → 30/04/19
Project: EU

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Chua, W., Khashaba, A., Canagarajah, H., Nielsen, J. C., di Biase, L., Haeusler, K. G., Hindricks, G., Mont, L., Piccini, J., Schnabel, R. B., Schotten, U., Wienhues-Thelen, U.-H., Zeller, T., Fabritz, L., & Kirchhof, P. (2024). Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study. Europace, 26(2), Article euae028. https://doi.org/10.1093/europace/euae028

@article{c163f3ee24d741e1bcbd1f67871d205d,

title = "Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study",

abstract = "Aims: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study.Methods and results: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations. Conclusion: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.",

keywords = "Ablation, Angiopoietin 2, Rhythm control, Bone morphogenetic protein 10, Atrial fibrillation, N-Terminal pro-B-type natriuretic peptide",

author = "Winnie Chua and Alya Khashaba and Hansel Canagarajah and Nielsen, {Jens Cosedis} and {di Biase}, Luigi and Haeusler, {Karl Georg} and Gerhard Hindricks and Lluis Mont and Jonathan Piccini and Schnabel, {Renate B} and Ulrich Schotten and Ursula-Henrike Wienhues-Thelen and Tanja Zeller and Larissa Fabritz and Paulus Kirchhof",

note = "Funding: AXAFA–AFNET5 received support from BMS/Pfizer and the German Centre for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK). The analyses reported here were supported in part by European Union-funded CATCH ME (grant agreement no. 633196) and MAESTRIA (grant agreement 965286), both to P.K., U.S., and L.F. Biomolecule quantification was performed by Roche Diagnostics as an in-kind donation to the CATCH ME project. J.C.N. was supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658) outside this work. U.-H.W.-T. is an employee of Roche Diagnostics.",

year = "2024",

month = feb,

doi = "10.1093/europace/euae028",

language = "English",

volume = "26",

journal = "Europace",

issn = "1099-5129",

publisher = "Oxford University Press",

number = "2",

}

Chua, W, Khashaba, A, Canagarajah, H, Nielsen, JC, di Biase, L, Haeusler, KG, Hindricks, G, Mont, L, Piccini, J, Schnabel, RB, Schotten, U, Wienhues-Thelen, U-H, Zeller, T, Fabritz, L & Kirchhof, P 2024, 'Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study', Europace, vol. 26, no. 2, euae028. https://doi.org/10.1093/europace/euae028

TY - JOUR

T1 - Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation

T2 - AXAFA biomolecule study

AU - Chua, Winnie

AU - Khashaba, Alya

AU - Canagarajah, Hansel

AU - Nielsen, Jens Cosedis

AU - di Biase, Luigi

AU - Haeusler, Karl Georg

AU - Hindricks, Gerhard

AU - Mont, Lluis

AU - Piccini, Jonathan

AU - Schnabel, Renate B

AU - Schotten, Ulrich

AU - Wienhues-Thelen, Ursula-Henrike

AU - Zeller, Tanja

AU - Fabritz, Larissa

AU - Kirchhof, Paulus

N1 - Funding: AXAFA–AFNET5 received support from BMS/Pfizer and the German Centre for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK). The analyses reported here were supported in part by European Union-funded CATCH ME (grant agreement no. 633196) and MAESTRIA (grant agreement 965286), both to P.K., U.S., and L.F. Biomolecule quantification was performed by Roche Diagnostics as an in-kind donation to the CATCH ME project. J.C.N. was supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658) outside this work. U.-H.W.-T. is an employee of Roche Diagnostics.

PY - 2024/2

Y1 - 2024/2

N2 - Aims: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study.Methods and results: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations. Conclusion: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.

AB - Aims: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study.Methods and results: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations. Conclusion: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.

KW - Ablation

KW - Angiopoietin 2

KW - Rhythm control

KW - Bone morphogenetic protein 10

KW - Atrial fibrillation

KW - N-Terminal pro-B-type natriuretic peptide

U2 - 10.1093/europace/euae028

DO - 10.1093/europace/euae028

M3 - Article

SN - 1099-5129

VL - 26

JO - Europace

JF - Europace

IS - 2

M1 - euae028

ER -

Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study

Abstract

Bibliographical note

Keywords

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Projects

MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation

H2020_COLLAB_CATCH ME_(LEAD)

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