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; George 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, George Gkoutos, Andreas Goette, Eduard Guasch, Stéphane Hatem, Andreas Metzner, Lluís Mont, Vaishnavi Ameya Murukutla, Julius Obergassel, Andreas Rillig, Moritz F SinnerRenate 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 › Academic › peer-review

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, 46% 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] 0.76 [95% confidence interval 0.65-0.89], p=0.001), bone morphogenetic protein 10 (BMP10) (OR 0.83 [0.71-0.97], p=0.017) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR 0.73 [0.60-0.88], p=0.001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (pinteraction=0.033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR 0.64 [0.51-0.80], p<0.001; early rhythm control: OR 0.90 [0.69-1.18], p=0.453). 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
Journal	European Heart Journal
DOIs	https://doi.org/10.1093/eurheartj/ehae611
Publication status	E-pub ahead of print - 31 Aug 2024

Keywords

angiopoietin 2
atrial fibrillation
blood biomarker
bone morphogenetic protein 10
natriuretic peptides
rhythm control
risk prediction
risk score
sinus rhythm

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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. Advance online publication. https://doi.org/10.1093/eurheartj/ehae611

@article{15388baf96a044318ecd35f046bf4736,

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, 46% 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] 0.76 [95% confidence interval 0.65-0.89], p=0.001), bone morphogenetic protein 10 (BMP10) (OR 0.83 [0.71-0.97], p=0.017) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR 0.73 [0.60-0.88], p=0.001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (pinteraction=0.033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR 0.64 [0.51-0.80], p<0.001; early rhythm control: OR 0.90 [0.69-1.18], p=0.453). 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 George 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 Ursula-Henrike Wienhues-Thelen and Antonia Zapf and Tanja Zeller and Paulus Kirchhof",

year = "2024",

month = aug,

day = "31",

doi = "10.1093/eurheartj/ehae611",

language = "English",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

}

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, U-H, 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. 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, George

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 - 2024/8/31

Y1 - 2024/8/31

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, 46% 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] 0.76 [95% confidence interval 0.65-0.89], p=0.001), bone morphogenetic protein 10 (BMP10) (OR 0.83 [0.71-0.97], p=0.017) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR 0.73 [0.60-0.88], p=0.001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (pinteraction=0.033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR 0.64 [0.51-0.80], p<0.001; early rhythm control: OR 0.90 [0.69-1.18], p=0.453). 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, 46% 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] 0.76 [95% confidence interval 0.65-0.89], p=0.001), bone morphogenetic protein 10 (BMP10) (OR 0.83 [0.71-0.97], p=0.017) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR 0.73 [0.60-0.88], p=0.001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (pinteraction=0.033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR 0.64 [0.51-0.80], p<0.001; early rhythm control: OR 0.90 [0.69-1.18], p=0.453). 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

U2 - 10.1093/eurheartj/ehae611

DO - 10.1093/eurheartj/ehae611

M3 - Article

SN - 0195-668X

JO - European Heart Journal

JF - European Heart Journal

ER -

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

Abstract

Keywords

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