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Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure

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Abstract

We investigated the clinical and prognostic implications of hyaluronic acid, a liver fibrosis marker, in patients with heart failure. We measured hyaluronic acid levels on admission in 655 hospitalized patients with heart failure between January 2015 and December 2019. Patients were stratified into three groups according to hyaluronic acid level: low (< 84.3 ng/mL, n = 219), middle (84.3–188.2 ng/mL, n = 218), and high (≥ 188.2 ng/mL, n = 218). The primary endpoint was all-cause death. The high hyaluronic acid group had higher N-terminal pro-brain-type natriuretic peptide levels, larger inferior vena cava, and shorter tricuspid annular plane systolic excursion than the other two groups. During the follow-up period (median 485 days), 132 all-cause deaths were observed: 27 (12.3%) in the low, 37 (17.0%) in the middle, and 68 (31.2%) in the high hyaluronic acid (P < 0.001) groups. Cox proportional hazards analysis revealed that higher log-transformed hyaluronic acid levels were significantly associated with all-cause death (hazard ratio, 1.38; 95% confidence interval, 1.15–1.66; P < 0.001). No significant interaction was observed between hyaluronic acid level and reduced/preserved left ventricular ejection fraction on all-cause death (P = 0.409). Hyaluronic acid provided additional prognostic predictability to pre-existing prognostic factors, including the fibrosis-4 index (continuous net reclassification improvement, 0.232; 95% confidence interval, 0.022–0.441; P = 0.030). In hospitalized patients with heart failure, hyaluronic acid was associated with right ventricular dysfunction and congestion and was independently associated with prognosis regardless of left ventricular ejection fraction.

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Acknowledgements

We are grateful to Naho Ito for her assistance.

Funding

This research was partially supported by the Japan Agency for Medical Research and Development (AMED) under grant number JP 22ek0109543. The sponsor did not play a role in the design, methods, subject recruitment, data collection, analysis, and preparation of the manuscript. This work was also partially supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (grant number 22K16152).

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Authors and Affiliations

  1. Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan

    Daichi Maeda, Yuya Matsue, Taishi Dotare, Tsutomu Sunayama, Takashi Iso, Shoichiro Yatsu, Sayaki Ishiwata, Yutaka Nakamura, Yuka Akama, Yuichiro Tsujimura, Shoko Suda, Takao Kato, Masaru Hiki, Takatoshi Kasai & Tohru Minamino

  2. Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Takatoshi Kasai

  3. Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo, Japan

    Tohru Minamino

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  1. Daichi Maeda
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Correspondence to Yuya Matsue.

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Y.M. has signed a collaborative research agreement with Siemens Healthcare Diagnostics K.K. The other authors declare that there are no conflicts of interest.

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This study was approved by the Institutional Review Board of Juntendo University Hospital (reference no. 20-020).

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Maeda, D., Matsue, Y., Dotare, T. et al. Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure. Heart Vessels 38, 1130–1137 (2023). https://doi.org/10.1007/s00380-023-02269-2

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