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Original research
Prognostic significance of natriuretic peptide levels in atrial fibrillation without heart failure
  1. Yasuhiro Hamatani1,
  2. Moritake Iguchi1,
  3. Kentaro Ueno2,
  4. Yuya Aono1,
  5. Masahiro Esato3,
  6. Hikari Tsuji4,
  7. Hiromichi Wada5,
  8. Koji Hasegawa5,
  9. Hisashi Ogawa1,
  10. Mitsuru Abe1,
  11. Satoshi Morita2,
  12. Masaharu Akao1
  1. 1Department of Cardiology, National Hospital Organisation Kyoto Medical Center, Kyoto, Japan
  2. 2Department of Biomedical Statistics and Bioinformatics, Kyoto University, Kyoto, Japan
  3. 3Department of Arrhythmia, Ogaki Tokushukai Hospital, Gifu, Japan
  4. 4Tsuji Clinic, Kyoto, Japan
  5. 5Division of Translational Research, National Hospital Organisation Kyoto Medical Center, Kyoto, Japan
  1. Correspondence to Dr Masaharu Akao, Cardiology, National Hospital Organisation Kyoto Medical Center, Kyoto 612-8555, Japan; akao{at}


Objectives Natriuretic peptides are an important prognostic marker in patients with heart failure (HF). However, little is known regarding their prognostic significance in patients with atrial fibrillation (AF) without HF and natriuretic peptides levels are underused in these patients in daily practice.

Methods The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We investigated patients with AF without HF (defined as prior HF hospitalisation, New York Heart Association functional class≥2 or left ventricular ejection fraction<40%) using the data of B-type natriuretic peptide (BNP, n=388) or N-terminal pro-B-type natriuretic peptide (NT-proBNP, n=771) at enrolment. BNPs were converted to NT-proBNP using a conversion formula. We divided the patients according to quartiles of NT-proBNP levels and compared the backgrounds and outcomes.

Results Of 1159 patients (mean age: 72.1±10.2 years, median CHA2DS2-VASc score: 3 and oral anticoagulant (OAC) prescription: 671 (56%)), the median NT-proBNP level was 488 (IQR 169–1015) ng/L. Patients with high NT-proBNP levels were older, had higher CHA2DS2-VASc scores and had more OAC prescription (all p<0.001). Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of stroke/systemic embolism, all-cause death and HF hospitalisation during a median follow-up period of 5.0 years (log rank, all p<0.001). Multivariable Cox regression analyses revealed that NT-proBNP levels were an independent predictor of adverse outcomes even after adjustment by various confounders.

Conclusion NT-proBNP levels are a significant prognostic marker for adverse outcomes in patients with AF without HF and may have clinical value.

Trial registration number UMIN000005834.

  • atrial fibrillation
  • heart failure
  • quality and outcomes of care

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  • Contributors YH analysed the data and wrote the paper. MI, YA, ME, HT, HW, KH, HO and MAb contributed to the acquisition of data and helped in the data analysis and interpretation. KU and SM contributed to the statistical analysis. MAk is a principal investigator of the Fushimi AF Registry and the corresponding author of this paper.

  • Funding The Fushimi AF Registry is supported by research funding from Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Novartis Pharma, MSD, Sanofi-Aventis and Takeda Pharmaceutical. The sponsors had no role in the design or conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. This study was partially supported by the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development, AMED (18ek0210082h0002, 18ek0210056h0003).

  • Competing interests MAk received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare and Daiichi-Sankyo.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethical committees of the Kyoto Medical Center and Ijinkai Takeda Hospital. Written informed consent was waived according to the ethical guidelines for epidemiological research issued by Ministry of Education, Culture, Sports, Science and Technology and Ministry of Health, Labour and Welfare, Japan.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data underlying this article cannot be shared publicly due to the privacy of individuals that participated in the study. The data will be shared on reasonable request to the corresponding author.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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