Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial

Lars Eckardt; Susanne Sehner; Anna Suling; Katrin Borof; Guenter Breithardt; Harry Crijns; Andreas Goette; Karl Wegscheider; Antonia Zapf; John Camm; Andreas Metzner; Paulus Kirchhof

doi:10.1093/eurheartj/ehac471

Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial

Lars Eckardt, Susanne Sehner, Anna Suling, Katrin Borof, Guenter Breithardt, Harry Crijns, Andreas Goette, Karl Wegscheider, Antonia Zapf, John Camm, Andreas Metzner, Paulus Kirchhof^*

^*Corresponding author for this work

Cardiovascular Sciences

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

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Abstract

AIMS: A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known how this outcome-reducing effect is mediated.

METHODS AND RESULTS: Using the Early treatment of Atrial Fibrillation for Stroke prevention Trial (EAST-AFNET 4) data set, potential mediators of the effect of ERC were identified in the total study population at 12-month follow up and further interrogated by use of a four-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared with usual care during the remainder of follow up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65-1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%. There was no difference in outcomes in patients who underwent AF ablation compared with those who did not undergo AF ablation.

CONCLUSION: The effectiveness of early rhythm control is mediated by the presence of sinus rhythm at 12 months in the EAST-AFNET 4 trial. Clinicians implementing ERC should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.

Original language	English
Pages (from-to)	4127-4144
Number of pages	18
Journal	European Heart Journal
Volume	43
Issue number	40
Early online date	29 Aug 2022
DOIs	https://doi.org/10.1093/eurheartj/ehac471
Publication status	Published - 21 Oct 2022

Bibliographical note

Keywords

Humans
Atrial Fibrillation/therapy
Catheter Ablation
Secondary Prevention
Stroke/prevention & control
Treatment Outcome

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10.1093/eurheartj/ehac471Licence: Creative Commons: Attribution (CC BY)

EckardtL2022AttainingFinal published version, 1.54 MBLicence: Creative Commons: Attribution (CC BY)

Defining clusters of patients with atrial fibrillation at risk of heart failure and death
Kirchhof, P. (Principal Investigator) & Gkoutos, G. (Researcher)
British Heart Foundation
1/07/20 → 30/06/21
Project: Research
Impact of chronic intermittent hypoxia on atrial resting membrane potential and Na 1.5 channel function: A new mechanism for causing atrial fibrillation
Kirchhof, P. (Principal Investigator) & Holmes, A. (Co-Investigator)
British Heart Foundation
1/10/17 → 18/07/21
Project: Research
Understanding the function of PITX2 in the adult left atrium
Kirchhof, P. (Principal Investigator) & Fabritz, L. (Co-Investigator)
British Heart Foundation
4/11/13 → 3/11/18
Project: Research

Cite this

Eckardt, L., Sehner, S., Suling, A., Borof, K., Breithardt, G., Crijns, H., Goette, A., Wegscheider, K., Zapf, A., Camm, J., Metzner, A., & Kirchhof, P. (2022). Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial. European Heart Journal, 43(40), 4127-4144. https://doi.org/10.1093/eurheartj/ehac471

@article{ecbab05a415c480a9d2542a991040c27,

title = "Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial",

abstract = "AIMS: A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known how this outcome-reducing effect is mediated.METHODS AND RESULTS: Using the Early treatment of Atrial Fibrillation for Stroke prevention Trial (EAST-AFNET 4) data set, potential mediators of the effect of ERC were identified in the total study population at 12-month follow up and further interrogated by use of a four-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared with usual care during the remainder of follow up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65-1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%. There was no difference in outcomes in patients who underwent AF ablation compared with those who did not undergo AF ablation.CONCLUSION: The effectiveness of early rhythm control is mediated by the presence of sinus rhythm at 12 months in the EAST-AFNET 4 trial. Clinicians implementing ERC should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.",

keywords = "Humans, Atrial Fibrillation/therapy, Catheter Ablation, Secondary Prevention, Stroke/prevention & control, Treatment Outcome",

author = "Lars Eckardt and Susanne Sehner and Anna Suling and Katrin Borof and Guenter Breithardt and Harry Crijns and Andreas Goette and Karl Wegscheider and Antonia Zapf and John Camm and Andreas Metzner and Paulus Kirchhof",

note = "{\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.",

year = "2022",

month = oct,

day = "21",

doi = "10.1093/eurheartj/ehac471",

language = "English",

volume = "43",

pages = "4127--4144",

journal = "European Heart Journal",

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Eckardt, L, Sehner, S, Suling, A, Borof, K, Breithardt, G, Crijns, H, Goette, A, Wegscheider, K, Zapf, A, Camm, J, Metzner, A & Kirchhof, P 2022, 'Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial', European Heart Journal, vol. 43, no. 40, pp. 4127-4144. https://doi.org/10.1093/eurheartj/ehac471

TY - JOUR

T1 - Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation

T2 - the EAST-AFNET 4 trial

AU - Eckardt, Lars

AU - Sehner, Susanne

AU - Suling, Anna

AU - Borof, Katrin

AU - Breithardt, Guenter

AU - Crijns, Harry

AU - Goette, Andreas

AU - Wegscheider, Karl

AU - Zapf, Antonia

AU - Camm, John

AU - Metzner, Andreas

AU - Kirchhof, Paulus

PY - 2022/10/21

Y1 - 2022/10/21

N2 - AIMS: A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known how this outcome-reducing effect is mediated.METHODS AND RESULTS: Using the Early treatment of Atrial Fibrillation for Stroke prevention Trial (EAST-AFNET 4) data set, potential mediators of the effect of ERC were identified in the total study population at 12-month follow up and further interrogated by use of a four-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared with usual care during the remainder of follow up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65-1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%. There was no difference in outcomes in patients who underwent AF ablation compared with those who did not undergo AF ablation.CONCLUSION: The effectiveness of early rhythm control is mediated by the presence of sinus rhythm at 12 months in the EAST-AFNET 4 trial. Clinicians implementing ERC should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.

AB - AIMS: A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known how this outcome-reducing effect is mediated.METHODS AND RESULTS: Using the Early treatment of Atrial Fibrillation for Stroke prevention Trial (EAST-AFNET 4) data set, potential mediators of the effect of ERC were identified in the total study population at 12-month follow up and further interrogated by use of a four-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared with usual care during the remainder of follow up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65-1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%. There was no difference in outcomes in patients who underwent AF ablation compared with those who did not undergo AF ablation.CONCLUSION: The effectiveness of early rhythm control is mediated by the presence of sinus rhythm at 12 months in the EAST-AFNET 4 trial. Clinicians implementing ERC should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.

KW - Humans

KW - Atrial Fibrillation/therapy

KW - Catheter Ablation

KW - Secondary Prevention

KW - Stroke/prevention & control

KW - Treatment Outcome

U2 - 10.1093/eurheartj/ehac471

DO - 10.1093/eurheartj/ehac471

M3 - Article

C2 - 36036648

SN - 0195-668X

VL - 43

SP - 4127

EP - 4144

JO - European Heart Journal

JF - European Heart Journal

IS - 40

ER -

Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial

Abstract

Bibliographical note

Keywords

Access to Document

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Projects

Defining clusters of patients with atrial fibrillation at risk of heart failure and death

Impact of chronic intermittent hypoxia on atrial resting membrane potential and Na 1.5 channel function: A new mechanism for causing atrial fibrillation

Understanding the function of PITX2 in the adult left atrium

Cite this