Elucidation of the mechanism of sinus node dysfunction caused by heart failure and development of new treatment methods

• Project/Area Number: 18K06856
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Oita University
• Principal Investigator: Shinohara Tetsuji 大分大学, 医学部, 助教 (60457629)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 心不全 / 洞結節機能障害 / 心房細動 / 糖尿病 / 洞不全症候群 / 洞結節機能

Outline of Final Research Achievements

Patients with heart failure often have sinus node dysfunction and rhythm abnormalities such as atrial fibrillation. It is known that the fibrosis and remodeling of sinus node cells.is involved in the mechanism.
Our study revealed that catheter ablation treatment can suppress heart failure re-admission in patients with atrial fibrillation who have heart failure. (Fukui A, Shinohara T, et al. J Cardiovasc Electrophysiol. 2020;31:682-688). We have previously demonstrated that diabetes, like heart failure, causes sinus node dysfunction. Furthermore, we reported that interleukin 10 replacement therapy is effective in maintaining sinus node function (Kondo H, Shinohara T, et al. Cardiovasc Res. 2019;115:57-70).

Academic Significance and Societal Importance of the Research Achievements

心不全患者は洞不全症候群および心房細動などのリズム異常を合併することが多い。そのメカニズムとして洞結節細胞の線維化およびリモデリングなどの関与が考えられている。
今回の我々の研究によって心不全を併発している心房細動患者に対してカテーテルアブレーション治療を行うことで、心房細動を治療することが心不全再入院を抑制できることを明らかにした。このことは、心不全がリズムに及ぼす影響を証明することができた。今後さらにそのメカニズムを明らかにしていくことで、新しい治療方法の開発につなげていくことができる。

Research Products

• [Journal Article] Catheter ablation of atrial fibrillation reduces heart failure rehospitalization in patients with heart failure with preserved ejection fraction (2020)
  • Author(s): Fukui Akira、Tanino Tomomi、Yamaguchi Takanori、Hirota Kei、Saito Shotaro、Okada Norihiro、Akioka Hidefumi、Shinohara Tetsuji、Yufu Kunio、Takahashi Naohiko
  • Journal Title: Journal of Cardiovascular Electrophysiology Volume: 31 Issue: 3 Pages: 682-688
  • DOI: 10.1111/jce.14369
  • Peer Reviewed
• [Journal Article] Interleukin-10 treatment attenuates sinus node dysfunction caused by streptozotocin-induced hyperglycaemia in mice (2018)
  • Author(s): Kondo Hidekazu、Kira Shintaro、Oniki Takahiro、Gotoh Koro、Fukui Akira、Abe Ichitaro、Ikebe Yuki、Kawano Kyoko、Saito Shotaro、Aoki Kohei、Okada Norihiro、Nagano Yasuko、Akioka Hidefumi、Shinohara Tetsuji、Akiyoshi Kumiko、Masaki Takayuki、Teshima Yasushi、Yufu Kunio、Nakagawa Mikiko、Takahashi Naohiko
  • Journal Title: Cardiovascular Research Volume: 115 Issue: 1 Pages: 57-70
  • DOI: 10.1093/cvr/cvy162
  • Peer Reviewed / Open Access
• [Presentation] Repeating glucose fluctuations impair morphological and functional integrity of sinus node in diabetic mice. (2020)
  • Author(s): Oniki T, Takahashi N.
  • Organizer: 第84回日本循環器学会学術集会 7.27-8.2,2020. 京都web開催
• [Presentation] Histamine 1 Receptor Signaling Exacerbates Pressure Overload-Mediated Acute Atrial Inflammation Leading to Atrial Fibrosis and Fibrillation (2019)
  • Author(s): Fukui A,Saito S,Kondo H,Shinohara T,Teshima Y,Takahashi N
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Human Epicardial Adipose Tissue Induces Rat Atrial Myocardial Fibrosis through Paracrine Effects: Results of Organo-culture Experiments (2019)
  • Author(s): Kira S,Abe I,Ishii Y,Miyoshi M,Oniki T,Fukui A Shinohara T,Teshima Y,Yufu K,Shimada T,Nakagawa M,Takahashi N
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Catheter Ablation of Atrial Fibrillation Reduces Heart Failure Re-hospitalization in Heart Failure with Preserved Ejection Fraction (HFpEF) Patients (2019)
  • Author(s): Akira Fukui, Tomomi Tanino, Takanori Yamaguchi, Tetsuji Shinohara, Kei Hirota, Shotaro Saito, Norihiro Okada, Hidefumi Akioka, Kunio Yufu, Naohiko Takahashi
  • Organizer: 第83回日本循環器学会学術集会