Importance of abdominal organ congestion and hypoperfusion in patients with heart failure, and association with hepatkine

• Project/Area Number: 20K16529
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Ichijo Yasuhiro 福島県立医科大学, 医学部, 病院助手 (00836041)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 心不全 / 多臓器連関 / 腹部超音波検査 / ヘパトカイン / 腹部超音波 / 臓器障害

Outline of Research at the Start

心不全はあらゆる心疾患の終末像であり、心機能低下による全身臓器のうっ血と低灌流を来す。腹部臓器のうっ血は心不全患者の予後と関連するが、うっ血と低灌流の双方の評価方法とその臨床的意義については確立されていない。本研究では、心不全患者における腹部臓器のうっ血および低灌流を、腹部超音波検査を用いて定量的に評価する方法を確立し、その指標が心不全の治療効果判定や予後予測に有用かを明らかにする。近年、肝臓由来液性因子のヘパトカインが、様々な生理活性を有すると報告されており、心臓-肝臓連関に着目して、血中ヘパトカイン濃度を測定し、うっ血や低灌流におけるヘパトカイン産生の差異を検討してその意義を明らかにする。

Outline of Final Research Achievements

We investigated a method for evaluating congestion and hypoperfusion of abdominal organs in heart failure patients, compared to control population, using abdominal ultrasonography. In addition, liver-derived proteins selenoprotein-P (Sep-P) and fetuin-A were measured and evaluated for their association with hemodynamics.
Serum Sep-P / fetuin-A was significantly higher / lower in the heart failure group than in the control group. Furthermore, Sep-P / fetuin-A was higher / lower in the hepatic hypoperfusion group regardless of hepatic congestion. Heart failure re-exacerbation events increased in the Sep-P high-value group and in the fetuin-A low-value group, compared to the Sep-P low-value group and the fetuin-A high-value group.

Academic Significance and Societal Importance of the Research Achievements

心不全は心臓のポンプ機能低下により全身臓器のうっ血と低灌流を来たし、多臓器不全は心不全の不良な予後と関連している。しかし、腹部臓器の結構動態を評価する非侵襲的手法は確立されていない。また肝臓由来液性因子であるヘパトカインが恒常性維持に重要な役割を果たすことが分かってきたが、肝臓のうっ血や低灌流によるヘパトカイン分泌異常などの詳細は検討されていない。
本研究では腹部超音波検査による非侵襲的な腹部臓器の血行動態評価法の有効性が示唆された。また既知のヘパトカインSelenoprotein-P/fetuin-Aの、肝血行動態との関連、および心不全・多臓器連関のバイオマーカーとしての有益性が示唆された。

Research Products

• [Journal Article] Renal Venous Stasis Index Reflects Renal Congestion and Predicts Adverse Outcomes in Patients With Heart Failure (2022)
  • Author(s): Ohara Himika、Yoshihisa Akiomi、Horikoshi Yuko、Ishibashi Shinji、Matsuda Mitsuko、Yamadera Yukio、Sugawara Yukiko、Ichijo Yasuhiro、Hotsuki Yu、Watanabe Koichiro、Sato Yu、Misaka Tomofumi、Kaneshiro Takashi、Oikawa Masayoshi、Kobayashi Atsushi、Takeishi Yasuchika
  • Journal Title: Frontiers in Cardiovascular Medicine Volume: 9 Pages: 772466-772466
  • DOI: 10.3389/fcvm.2022.772466
  • Open Access
• [Journal Article] Decreases in hepatokine Fetuin-A levels are associated with hepatic hypoperfusion and predict cardiac outcomes in patients with heart failure. (In press) (2022)
  • Author(s): Tomita Yusuke、Misaka Tomofumi、Yoshihisa Akiomi、Ichijo Yasuhiro、Ishibashi Shinji、Matsuda Mitsuko、Yamadera Yukio、Ohara Himika、Sugawara Yukiko、Hotsuki Yu、Watanabe Koichiro、Anzai Fumiya、Sato Yu、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Takeishi Yasuchika
  • Journal Title: Clinical Research in Cardiology Volume: - Issue: 10 Pages: 1104-1112
  • DOI: 10.1007/s00392-022-02023-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Increases in hepatokine Selenoprotein P levels are associated with hepatic hypoperfusion and predict adverse prognosis in patients with heart failure (In press) (2022)
  • Author(s): Rhyohei Takeishi, Tomofumi Misaka, Yasuhiro Ichijo, Shinji Ishibashi, Mitsuko Matsuda, Yukio Yamadera, Himika Ohara, Yukiko Sugawara, Yu Hotsuki, Koichiro Watanabe, Fumiya Anzai, Yu Sato, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Kazuhiko Nakazato, Akiomi Yoshihisa, Yasuchika Takeishi
  • Journal Title: Journal of the Heart Association Volume: -
• [Journal Article] Impaired frontal brain activity in patients with heart failure assessed by near-infrared spectroscopy. (2020)
  • Author(s): Ichijo Y, Kono S, Yoshihisa A, Misaka T, Kaneshiro T, Oikawa M, Miura I, Yabe H, Takeishi Y
  • Journal Title: J Am Heart Assoc Volume: 9 Issue: 3
  • DOI: 10.1161/jaha.119.014564
  • Peer Reviewed / Open Access
• [Journal Article] Shear Wave Dispersion Predicts Liver Fibrosis and Adverse Outcomes in Patients with Heart Failure (2020)
  • Author(s): Himika Ohara, Akiomi Yoshihisa, Shinji Ishibashi, Mitsuko Matsuda, Yukio Yamadera, Yukiko Sugawara, Yasuhiro Ichijo, Yu Hotsuki, Koichiro Watanabe, Fumiya Anzai, Yu Sato, Yusuke Kimishima, Tetsuro Yokokawa, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi and Yasuchika Takeishi.
  • Journal Title: J Clin Med Volume: 9 Issue: 12 Pages: 3953-3953
  • DOI: 10.3390/jcm9123953
  • Peer Reviewed / Open Access
• [Journal Article] Intrarenal Doppler ultrasonography reflects hemodynamics and predicts prognosis in patients with heart failure. (2020)
  • Author(s): Yoshihisa A, Watanabe K, Sato Y, Ishibashi S, Matsuda M, Yamadera Y, Ichijo Y, Yokokawa T, Misaka T, Oikawa M, Kobayashi A, Takeishi Y.
  • Journal Title: Scientific Report Volume: 10 Issue: 1 Pages: 22257-22257
  • DOI: 10.1038/s41598-020-79351-6
  • Peer Reviewed / Open Access
• [Presentation] Hepatokine Selenoprotein P is associated with hypoperfusion and predicts adverse prognosis in heart failure patients (2021)
  • Author(s): Yasuhiro Ichijo, Tomofumi Misaka, Akiomi Yoshihisa, Yu Hotsuki, Koichiro Watanbe, Fumiya Anzai, Yu Sato, Yusuke Kimishima, Tetsuro Yokokawa, Masayoshi Oikawa, Atsushi Kobayashi, Yasuchika Takeishi
  • Organizer: 日本循環器学会
• [Presentation] Decrease in hepatokine fetuin-a is associated with hepatic hypoperfusion in patients with heart failure. (2021)
  • Author(s): Tomita Y, Misaka T, Yoshihisa A, Ichijo Y, Anzai F, Ohara H, Sugawara Y, Hotsuki Y, Watanabe K, Sato Y, Oikawa M, Kobayashi A, Takeishi Y
  • Organizer: American Heart Association
  • Int'l Joint Research
• [Presentation] Serum hepatokine selenoprotein P is upregulated by hepatic hypoperfusion and predicts adverse prognosis in heart failure patients (2020)
  • Author(s): Yasuhiro Ichijo, Tomofumi Misaka, Akiomi Yoshihisa, Yu Hotsuki, Koichiro Watanabe, Yu Sato, Yusuke Kimishima, Tetsuro Yokokawa, Masayoshi Oikawa, Atsushi Kobayashi, Yasuchika Takeishi
  • Organizer: American Heart Association
  • Int'l Joint Research
• [Remarks] 福島県立医科大学循環器内科学講座ホームページ
  • URL: https://www.fmu.ac.jp/home/int-med1/intmed1main.htm