Research for constructing a new treatment strategy for acute heart failure-Application of diuretic responsiveness and biomarkers-

• Project/Area Number: 17K09002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Yoshihara Fumiki 国立研究開発法人国立循環器病研究センター, 病院, 部長 (70393220)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心腎連関症候群 / 急性腎障害 / 尿バイオマーカー / 利尿薬反応性 / 循環器・高血圧

Outline of Final Research Achievements

Acute heart failure is a disease that causes respiratory distress and generalized edema, and causes death if proper treatment is not performed. Increasing number of patients with heart failure due to aging is one of the social problems in Japan. Acute kidney injury is easy to be associated with acute heart failure, and is one of the important factors that makes it difficult to treat heart failure. Here, we investigated the factors involved in the progression of acute heart failure patients with acute kidney injury. The reactivity of diuretics (volume of urine per unit dose), the degree of regurgitation of the tricuspid valve separating the right atrium and the right ventricle, and urinary biomarkers were examined.

Academic Significance and Societal Importance of the Research Achievements

急性腎障害を合併した場合、どういう特徴を持つ患者が重症化の危険性が高いのかを知ることが出来れば、適切な治療方法を選択する上で重要な情報に成り得る。利尿薬の反応性（単位投与量当たりの尿量）が低く、三尖弁の逆流の程度が大きい患者群で重症化リスクが高いことを明らかにした。また、血中Ｂ型ナトリウム利尿ペプチド濃度が高く、心臓カテーテル治療後の尿中Ｌ型脂肪酸結合蛋白レベルが高い患者群は、腎障害を合併し易いことを同定した。さらに尿アドレノメデュリンレベルも低Ｋ血症と関連を有し上昇することを同定した。今後は如何なる治療介入が心不全の重症化や腎障害の進行を抑制するかを明らかにすることが必要である。

Research Products

• [Journal Article] Association Between Circadian Hemodynamic Characteristics and Target Organ Damage in Patients With Essential Hypertension (2019)
  • Author(s): Kusunoki Hiroshi、Iwashima Yoshio、Kawano Yuhei、Hayashi Shin-ichiro、Kishida Masatsugu、Horio Takeshi、Shinmura Ken、Yoshihara Fumiki
  • Journal Title: American Journal of Hypertension Volume: 32 Issue: 8 Pages: 742-751
  • DOI: 10.1093/ajh/hpz088
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER). (2018)
  • Author(s): Yoshihara F, Imazu M, Hamasaki T, Anzai T, Yasuda S, Ito S, Yamamoto H, Hashimura K, Yasumura Y, Mori K, Watanabe M, Asakura M, Kitakaze M
  • Journal Title: Cardiovasc Drugs Ther. Volume: 32 Pages: 183-190
  • Peer Reviewed
• [Journal Article] Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide. (2017)
  • Author(s): Takaya Y, Yoshihara F, Yokoyama H, Kanzaki H, Kitakaze M, Goto Y, Anzai T, Yasuda S, Ogawa H, Kawano Y, Kangawa K.
  • Journal Title: Heart Vessels Volume: 32 Issue: 8 Pages: 932-943
  • DOI: 10.1007/s00380-017-0954-y
  • Peer Reviewed
• [Presentation] Impact of Diuretic Response on Differentiation of Acute Kidney Injury at Risk of Mortality in Acute Decompensated Heart Failure Patients (2019)
  • Author(s): 高谷陽一 吉原史樹 横山広行 神崎秀明 北風政史 後藤葉一 安田 聡 小川久雄 安斉俊久
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Impact of Acute Kidney Injury on Mortality in Patients with Acute Decompensated Heart Failure Complicated with Tricupid Regurgitation (2019)
  • Author(s): 高谷陽一 吉原史樹 横山広行 神崎秀明 北風政史 後藤葉一 安田 聡 小川久雄 安斉俊久
  • Organizer: 第83回日本循環器学会学術集会