Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study

Larissa Fabritz; Christoph Al-Taie; Katrin Borof; Günter Breithardt; A. John Camm; Harry J.G.M. Crijns; Victor Roth Cardoso; Winnie Chua; Silke Van Elferen; Lars Eckardt; Georgios Gkoutos; Andreas Goette; Eduard Guasch; Stéphane Hatem; Andreas Metzner; Lluís Mont; Vaishnavi Ameya Murukutla; Julius Obergassel; Andreas Rillig; Moritz F. Sinner; Renate B. Schnabel; Ulrich Schotten; Laura C. Sommerfeld; Ursula Henrike Wienhues-Thelen; Antonia Zapf; Tanja Zeller; Paulus Kirchhof

doi:10.1093/eurheartj/ehae611

Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study

Larissa Fabritz
, Christoph Al-Taie
, Katrin Borof
, Günter Breithardt
, A. John Camm
, Harry J.G.M. Crijns
, Victor Roth Cardoso
, Winnie Chua
, Silke Van Elferen
, Lars Eckardt
, Georgios Gkoutos
, Andreas Goette
, Eduard Guasch
, Stéphane Hatem
, Andreas Metzner
, Lluís Mont
, Vaishnavi Ameya Murukutla
, Julius Obergassel
, Andreas Rillig
, Moritz F. Sinner

Renate B. Schnabel, Ulrich Schotten, Laura C. Sommerfeld, Ursula Henrike Wienhues-Thelen, Antonia Zapf, Tanja Zeller, Paulus Kirchhof^*

^*Corresponding author for this work

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

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Abstract

Background and Aims: In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm control therapy. Predictors of attaining sinus rhythm at follow-up are not well known.

Methods: To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 45% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets.

Results: Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR]. 76 [95% confidence interval. 65-.89], P <. 001), bone morphogenetic protein 10 (BMP10) (OR. 83 [.71-.97], P =. 017), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR. 73 [.60-.88], P <. 001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (P_interaction =. 033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR. 64 [.51-.80], P <. 001; early rhythm control: OR. 90 [.69-1.18], P =. 453). External validation confirmed that low concentrations of ANGPT2, BMP10, and NT-proBNP predict sinus rhythm during follow-up.

Conclusions: Low concentrations of ANGPT2, BMP10, and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.

Original language	English
Pages (from-to)	5002-5019
Number of pages	18
Journal	European Heart Journal
Volume	45
Issue number	47
Early online date	31 Aug 2024
DOIs	https://doi.org/10.1093/eurheartj/ehae611
Publication status	Published - 14 Dec 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Angiopoietin 2
Atrial fibrillation
Blood biomarker
Bone morphogenetic protein 10
Natriuretic peptides
Rhythm control
Risk prediction
Risk score
Sinus rhythm

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

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FabritzL2024BiomarkerFinal published version, 1.92 MBLicence: Creative Commons: Attribution-NonCommercial (CC BY-NC)

1 Active
2 Finished

Hypermarker: Personalised pharmacometabolomic optimisation of treatment for hypertension
Acharjee, A. (Co-Investigator), Gkoutos, G. (Co-Investigator), Mobley, A. (Co-Investigator) & Kotecha, D. (Principal Investigator)
UKRI Horizon Europe Underwriting Innovate UK
1/01/23 → 31/12/26
Project: Research
MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation
Kirchhof, P. (Researcher), Gkoutos, G. (Principal Investigator) & Fabritz, L. (Researcher)
European Commission
1/03/21 → 31/08/26
Project: EU
H2020_COLLAB_CATCH ME_(LEAD)
Kirchhof, P. (Principal Investigator), Fabritz, L. (Co-Investigator), Hemming, K. (Co-Investigator) & Deeks, J. (Co-Investigator)
European Commission
1/05/15 → 30/04/19
Project: EU

Cite this

Fabritz, L., Al-Taie, C., Borof, K., Breithardt, G., Camm, A. J., Crijns, H. J. G. M., Roth Cardoso, V., Chua, W., Van Elferen, S., Eckardt, L., Gkoutos, G., Goette, A., Guasch, E., Hatem, S., Metzner, A., Mont, L., Murukutla, V. A., Obergassel, J., Rillig, A., ... Kirchhof, P. (2024). Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study. European Heart Journal, 45(47), 5002-5019. https://doi.org/10.1093/eurheartj/ehae611

@article{7a24f32c9ed24256bfcab425b3734dd6,

title = "Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study",

abstract = "Background and Aims: In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm control therapy. Predictors of attaining sinus rhythm at follow-up are not well known. Methods: To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 45\% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets. Results: Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR]. 76 [95\% confidence interval. 65-.89], P <. 001), bone morphogenetic protein 10 (BMP10) (OR. 83 [.71-.97], P =. 017), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR. 73 [.60-.88], P <. 001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (Pinteraction =. 033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR. 64 [.51-.80], P <. 001; early rhythm control: OR. 90 [.69-1.18], P =. 453). External validation confirmed that low concentrations of ANGPT2, BMP10, and NT-proBNP predict sinus rhythm during follow-up. Conclusions: Low concentrations of ANGPT2, BMP10, and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.",

keywords = "Angiopoietin 2, Atrial fibrillation, Blood biomarker, Bone morphogenetic protein 10, Natriuretic peptides, Rhythm control, Risk prediction, Risk score, Sinus rhythm",

author = "Larissa Fabritz and Christoph Al-Taie and Katrin Borof and G{\"u}nter Breithardt and Camm, \{A. John\} and Crijns, \{Harry J.G.M.\} and \{Roth Cardoso\}, Victor and Winnie Chua and \{Van Elferen\}, Silke and Lars Eckardt and Georgios Gkoutos and Andreas Goette and Eduard Guasch and St{\'e}phane Hatem and Andreas Metzner and Llu{\'i}s Mont and Murukutla, \{Vaishnavi Ameya\} and Julius Obergassel and Andreas Rillig and Sinner, \{Moritz F.\} and Schnabel, \{Renate B.\} and Ulrich Schotten and Sommerfeld, \{Laura C.\} and Wienhues-Thelen, \{Ursula Henrike\} and Antonia Zapf and Tanja Zeller and Paulus Kirchhof",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2024",

month = dec,

day = "14",

doi = "10.1093/eurheartj/ehae611",

language = "English",

volume = "45",

pages = "5002--5019",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "47",

}

Fabritz, L, Al-Taie, C, Borof, K, Breithardt, G, Camm, AJ, Crijns, HJGM, Roth Cardoso, V, Chua, W, Van Elferen, S, Eckardt, L, Gkoutos, G, Goette, A, Guasch, E, Hatem, S, Metzner, A, Mont, L, Murukutla, VA, Obergassel, J, Rillig, A, Sinner, MF, Schnabel, RB, Schotten, U, Sommerfeld, LC, Wienhues-Thelen, UH, Zapf, A, Zeller, T & Kirchhof, P 2024, 'Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study', European Heart Journal, vol. 45, no. 47, pp. 5002-5019. https://doi.org/10.1093/eurheartj/ehae611

TY - JOUR

T1 - Biomarker-based prediction of sinus rhythm in atrial fibrillation patients

T2 - the EAST-AFNET 4 biomolecule study

AU - Fabritz, Larissa

AU - Al-Taie, Christoph

AU - Borof, Katrin

AU - Breithardt, Günter

AU - Camm, A. John

AU - Crijns, Harry J.G.M.

AU - Roth Cardoso, Victor

AU - Chua, Winnie

AU - Van Elferen, Silke

AU - Eckardt, Lars

AU - Gkoutos, Georgios

AU - Goette, Andreas

AU - Guasch, Eduard

AU - Hatem, Stéphane

AU - Metzner, Andreas

AU - Mont, Lluís

AU - Murukutla, Vaishnavi Ameya

AU - Obergassel, Julius

AU - Rillig, Andreas

AU - Sinner, Moritz F.

AU - Schnabel, Renate B.

AU - Schotten, Ulrich

AU - Sommerfeld, Laura C.

AU - Wienhues-Thelen, Ursula Henrike

AU - Zapf, Antonia

AU - Zeller, Tanja

AU - Kirchhof, Paulus

PY - 2024/12/14

Y1 - 2024/12/14

N2 - Background and Aims: In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm control therapy. Predictors of attaining sinus rhythm at follow-up are not well known. Methods: To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 45% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets. Results: Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR]. 76 [95% confidence interval. 65-.89], P <. 001), bone morphogenetic protein 10 (BMP10) (OR. 83 [.71-.97], P =. 017), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR. 73 [.60-.88], P <. 001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (Pinteraction =. 033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR. 64 [.51-.80], P <. 001; early rhythm control: OR. 90 [.69-1.18], P =. 453). External validation confirmed that low concentrations of ANGPT2, BMP10, and NT-proBNP predict sinus rhythm during follow-up. Conclusions: Low concentrations of ANGPT2, BMP10, and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.

AB - Background and Aims: In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm control therapy. Predictors of attaining sinus rhythm at follow-up are not well known. Methods: To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 45% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets. Results: Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR]. 76 [95% confidence interval. 65-.89], P <. 001), bone morphogenetic protein 10 (BMP10) (OR. 83 [.71-.97], P =. 017), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR. 73 [.60-.88], P <. 001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (Pinteraction =. 033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR. 64 [.51-.80], P <. 001; early rhythm control: OR. 90 [.69-1.18], P =. 453). External validation confirmed that low concentrations of ANGPT2, BMP10, and NT-proBNP predict sinus rhythm during follow-up. Conclusions: Low concentrations of ANGPT2, BMP10, and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.

KW - Angiopoietin 2

KW - Atrial fibrillation

KW - Blood biomarker

KW - Bone morphogenetic protein 10

KW - Natriuretic peptides

KW - Rhythm control

KW - Risk prediction

KW - Risk score

KW - Sinus rhythm

UR - https://www.scopus.com/pages/publications/85210100722

U2 - 10.1093/eurheartj/ehae611

DO - 10.1093/eurheartj/ehae611

M3 - Article

C2 - 39215973

AN - SCOPUS:85210100722

SN - 0195-668X

VL - 45

SP - 5002

EP - 5019

JO - European Heart Journal

JF - European Heart Journal

IS - 47

ER -

Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Projects

Hypermarker: Personalised pharmacometabolomic optimisation of treatment for hypertension

MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation

H2020_COLLAB_CATCH ME_(LEAD)

Cite this