Heart rate in early rhythm control therapy in patients with atrial fibrillation

Tim Koldenhof; Katrin Borof; Isabelle C Van Gelder; Robert G Tieleman; Marc D Lemoine; Renate B Schnabel; Karl Wegscheider; Paulus Kirchhof; Michiel Rienstra; for the EAST-AFNET 4 Trial Investigators

doi:10.1136/heartjnl-2025-326878

Heart rate in early rhythm control therapy in patients with atrial fibrillation

Tim Koldenhof
, Katrin Borof
, Isabelle C Van Gelder
, Robert G Tieleman
, Marc D Lemoine
, Renate B Schnabel
, Karl Wegscheider
, Paulus Kirchhof
, Michiel Rienstra^*
, for the EAST-AFNET 4 Trial Investigators

^*Corresponding author for this work

Cardiovascular Sciences

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

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Abstract

Background Preventing high heart rates in atrial fibrillation (AF) is recommended to reduce AF-related symptoms and morbidity. Evidence on a strong relationship between lower heart rate during AF and a reduction in symptoms or cardiovascular complications is, however, lacking.

Methods This Early Treatment of Atrial Fibrillation for Stroke Prevention Trial analysis compared symptoms, treatment strategy and the composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome between patients with a heart rate <110 beats per minute and ≥110 beats per minute at baseline.

Results At baseline, 772 patients were in AF and had information on heart rate available. Mean age was 70.8±7.8 years, 305 (40%) were women, 385 (50%) were randomised to early rhythm control and 506 (66%) patients had a heart rate <110 beats per minute. Patients with a heart rate ≥110 beats per minute at baseline were more likely to have symptomatic AF (78% vs 62%, p<0.001) and more likely to have severe symptomatic AF with a European Heart Rhythm Association score ≥3 (19% vs 12%, p=0.032). The primary outcome, a composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome, occurred in 116 patients with a heart rate <110 beats per minute (5.1 per 100 person-years) and 62 patients with a heart rate ≥110 beats per minute (5.1 per 100 person years). The HR of the primary outcome for patients with a heart rate ≥110 beats per minute compared with patients with a heart rate <110 beats per minute was 1.08 (95% CI 0.79 to 1.48).

Conclusion A high heart rate (≥110 beats per minute) during AF is associated with more and more severe AF-related symptoms. Cardiovascular event rates are not different between heart rates. Early rhythm control reduces outcomes in patients with high and low heart rates during AF.

Trial registration number NCT01288352.

Original language	English
Number of pages	6
Journal	Heart
Early online date	9 Feb 2026
DOIs	https://doi.org/10.1136/heartjnl-2025-326878
Publication status	E-pub ahead of print - 9 Feb 2026

Keywords

Atrial Fibrillation
Tachycardia, Supraventricular

Access to Document

10.1136/heartjnl-2025-326878Licence: None: All rights reserved

KolderhofT2026Heart_AAM
This article has been accepted for publication in Heart, 2026 following peer review, and the Version of Record can be accessed online at https://doi.org/10.1136/heartjnl-2025-326878. For the avoidance of doubt, this manuscript version is protected by copyright, including for uses related to text and data mining, AI training, and similar technologies.
Accepted author manuscript, 307 KBLicence: Other (please specify with Rights Statement)

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
H2020_COLLAB(IMI-JU)_BIGDATA@HEART
Kotecha, D. (Principal Investigator) & Kirchhof, P. (Co-Investigator)
European Commission
1/03/17 → 28/02/23
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

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title = "Heart rate in early rhythm control therapy in patients with atrial fibrillation",

abstract = "Background Preventing high heart rates in atrial fibrillation (AF) is recommended to reduce AF-related symptoms and morbidity. Evidence on a strong relationship between lower heart rate during AF and a reduction in symptoms or cardiovascular complications is, however, lacking. Methods This Early Treatment of Atrial Fibrillation for Stroke Prevention Trial analysis compared symptoms, treatment strategy and the composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome between patients with a heart rate <110 beats per minute and ≥110 beats per minute at baseline. Results At baseline, 772 patients were in AF and had information on heart rate available. Mean age was 70.8±7.8 years, 305 (40\%) were women, 385 (50\%) were randomised to early rhythm control and 506 (66\%) patients had a heart rate <110 beats per minute. Patients with a heart rate ≥110 beats per minute at baseline were more likely to have symptomatic AF (78\% vs 62\%, p<0.001) and more likely to have severe symptomatic AF with a European Heart Rhythm Association score ≥3 (19\% vs 12\%, p=0.032). The primary outcome, a composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome, occurred in 116 patients with a heart rate <110 beats per minute (5.1 per 100 person-years) and 62 patients with a heart rate ≥110 beats per minute (5.1 per 100 person years). The HR of the primary outcome for patients with a heart rate ≥110 beats per minute compared with patients with a heart rate <110 beats per minute was 1.08 (95\% CI 0.79 to 1.48). Conclusion A high heart rate (≥110 beats per minute) during AF is associated with more and more severe AF-related symptoms. Cardiovascular event rates are not different between heart rates. Early rhythm control reduces outcomes in patients with high and low heart rates during AF. Trial registration number NCT01288352.",

keywords = "Atrial Fibrillation, Tachycardia, Supraventricular",

author = "Tim Koldenhof and Katrin Borof and \{Van Gelder\}, \{Isabelle C\} and Tieleman, \{Robert G\} and Lemoine, \{Marc D\} and Schnabel, \{Renate B\} and Karl Wegscheider and Paulus Kirchhof and Michiel Rienstra and \{for the EAST-AFNET 4 Trial Investigators\}",

year = "2026",

month = feb,

day = "9",

doi = "10.1136/heartjnl-2025-326878",

language = "English",

journal = "Heart",

issn = "1355-6037",

publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Heart rate in early rhythm control therapy in patients with atrial fibrillation

AU - Koldenhof, Tim

AU - Borof, Katrin

AU - Van Gelder, Isabelle C

AU - Tieleman, Robert G

AU - Lemoine, Marc D

AU - Schnabel, Renate B

AU - Wegscheider, Karl

AU - Kirchhof, Paulus

AU - Rienstra, Michiel

AU - for the EAST-AFNET 4 Trial Investigators

PY - 2026/2/9

Y1 - 2026/2/9

N2 - Background Preventing high heart rates in atrial fibrillation (AF) is recommended to reduce AF-related symptoms and morbidity. Evidence on a strong relationship between lower heart rate during AF and a reduction in symptoms or cardiovascular complications is, however, lacking. Methods This Early Treatment of Atrial Fibrillation for Stroke Prevention Trial analysis compared symptoms, treatment strategy and the composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome between patients with a heart rate <110 beats per minute and ≥110 beats per minute at baseline. Results At baseline, 772 patients were in AF and had information on heart rate available. Mean age was 70.8±7.8 years, 305 (40%) were women, 385 (50%) were randomised to early rhythm control and 506 (66%) patients had a heart rate <110 beats per minute. Patients with a heart rate ≥110 beats per minute at baseline were more likely to have symptomatic AF (78% vs 62%, p<0.001) and more likely to have severe symptomatic AF with a European Heart Rhythm Association score ≥3 (19% vs 12%, p=0.032). The primary outcome, a composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome, occurred in 116 patients with a heart rate <110 beats per minute (5.1 per 100 person-years) and 62 patients with a heart rate ≥110 beats per minute (5.1 per 100 person years). The HR of the primary outcome for patients with a heart rate ≥110 beats per minute compared with patients with a heart rate <110 beats per minute was 1.08 (95% CI 0.79 to 1.48). Conclusion A high heart rate (≥110 beats per minute) during AF is associated with more and more severe AF-related symptoms. Cardiovascular event rates are not different between heart rates. Early rhythm control reduces outcomes in patients with high and low heart rates during AF. Trial registration number NCT01288352.

AB - Background Preventing high heart rates in atrial fibrillation (AF) is recommended to reduce AF-related symptoms and morbidity. Evidence on a strong relationship between lower heart rate during AF and a reduction in symptoms or cardiovascular complications is, however, lacking. Methods This Early Treatment of Atrial Fibrillation for Stroke Prevention Trial analysis compared symptoms, treatment strategy and the composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome between patients with a heart rate <110 beats per minute and ≥110 beats per minute at baseline. Results At baseline, 772 patients were in AF and had information on heart rate available. Mean age was 70.8±7.8 years, 305 (40%) were women, 385 (50%) were randomised to early rhythm control and 506 (66%) patients had a heart rate <110 beats per minute. Patients with a heart rate ≥110 beats per minute at baseline were more likely to have symptomatic AF (78% vs 62%, p<0.001) and more likely to have severe symptomatic AF with a European Heart Rhythm Association score ≥3 (19% vs 12%, p=0.032). The primary outcome, a composite of death from cardiovascular causes, stroke or hospitalisation with worsening of heart failure or acute coronary syndrome, occurred in 116 patients with a heart rate <110 beats per minute (5.1 per 100 person-years) and 62 patients with a heart rate ≥110 beats per minute (5.1 per 100 person years). The HR of the primary outcome for patients with a heart rate ≥110 beats per minute compared with patients with a heart rate <110 beats per minute was 1.08 (95% CI 0.79 to 1.48). Conclusion A high heart rate (≥110 beats per minute) during AF is associated with more and more severe AF-related symptoms. Cardiovascular event rates are not different between heart rates. Early rhythm control reduces outcomes in patients with high and low heart rates during AF. Trial registration number NCT01288352.

KW - Atrial Fibrillation

KW - Tachycardia, Supraventricular

U2 - 10.1136/heartjnl-2025-326878

DO - 10.1136/heartjnl-2025-326878

M3 - Article

SN - 1355-6037

JO - Heart

JF - Heart

ER -

Heart rate in early rhythm control therapy in patients with atrial fibrillation

Abstract

Keywords

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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

H2020_COLLAB(IMI-JU)_BIGDATA@HEART

Understanding the function of PITX2 in the adult left atrium

Cite this