Thromb Haemost 2023; 123(09): 920-929
DOI: 10.1055/s-0043-1768580
Stroke, Systemic or Venous Thromboembolism

Visit-to-Visit Heart Rate Variability in the Prediction of Clinical Outcomes of Patients with Atrial Fibrillation

Rungroj Krittayaphong
1   Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Warangkna Boonyapisit
1   Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Poom Sairat
1   Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2   Liverpool Centre for Cardiovascular Science, at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
3   Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
› Author Affiliations
Funding This study was funded by the Health Systems Research Institute (HSRI) (grant no. 59–053), and grants from the Heart Association of Thailand under the Royal Patronage of H.M. the King. None of the aforementioned funding sources influenced any aspect of this study or the decision of the authors to submit this manuscript for publication.


Background Visit-to-visit heart rate variability (VVV-HR) has been associated with adverse cardiovascular outcomes. We aimed to determine the predictive value of VVV-HR for adverse clinical outcomes in patients with nonvalvular atrial fibrillation (AF).

Methods We used data from a prospective multicenter AF registry of 27 hospitals in Thailand during 2014 to 2017. After the baseline visit, patients were followed up every 6 months until 3 years. VVV-HR was calculated from the standard deviation of heart rate data from baseline visit and every follow-up visit. VVV-HR was categorized into four groups according to the quartiles. Clinical outcomes were all-cause death, ischemic stroke/systemic embolism (SE), and heart failure. Cox proportional hazard models were used for multivariable analysis.

Results There were a total of 3,174 patients (mean age: 67.7 years; 41.8% female). The incidence rates of all-cause death, ischemic stroke/SE, and heart failure were 3.10 (2.74–3.49), 1.42 (1.18–1.69), and 2.09 (1.80–2.42) per 100 person-years respectively. The average heart rate was 77.8 ± 11.0 bpm and the average of standard deviation of heart rate was 11.0 ± 5.9 bpm. VVV-HR Q4 was an independent predictor of all-cause death, ischemic stroke/SE, and heart failure with adjusted hazard ratios of 1.45 (95% confidence interval: 1.07–1.98), 2.02 (1.24–3.29), and 2.63 (1.75–3.96), respectively. VVV-HR still remained a significant predictor of clinical outcomes when analyzed based on coefficient of variation and variability independent of mean.

Conclusion VVV-HR is an independent predictor for adverse clinical outcomes in patients with AF. A J-curve appearance was demonstrated for the effect of VVV-HR on all-cause death.

Data Availability Statement

The dataset that was used to support the results and conclusion of this study is included within the manuscript. Additional data are available upon contacting the corresponding author with reasonable request.

Authors' Contribution

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

The review process for this paper was fully handled by Christian Weber, Editor in Chief.

Supplementary Material

Publication History

Received: 31 December 2022

Accepted: 31 March 2023

Article published online:
28 April 2023

© 2023. Thieme. All rights reserved.

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