Exploratory study for clinical pathophysiology of heart failure with preserved ejection (HFpEF) and development for experimental model of HFpEF.

• Project/Area Number: 15K09109
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Takahama Hiroyuki 国立研究開発法人国立循環器病研究センター, 病院, 医師 (10570301)
• Co-Investigator(Renkei-kenkyūsha): Anzai Toshihisa 北海道大学, 大学院・医学研究院, 教授 (60232089) ; Kitakaze Masafumi 国立研究開発法人・国立循環器病研究センター, 研究開発基盤センター, 部長 (20294069) ; Minamino Naoto 国立研究開発法人・国立循環器病研究センター, その他, 部長 (50124839) ; Ueda Hatsue 国立研究開発法人・国立循環器病研究センター, 病院, 部長 (40522983)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 拡張期心不全 / BNP / バイオマーカー / 心筋生検 / 心不全モデル

Outline of Final Research Achievements

We performed the histological analysis and the study using biomarkers such as B-type natriuretic peptide (BNP) for patients with heart failure with preserved ejection fraction (EF)(HFpEF). Immuno-histological staining for microvascular endothelium was successful. We are now performing statistical analysis for the microvascular density. Additionally, we found that bioactive BNP ratio differ between patients with HFpEF and heart failure with reduced EF, and reported it.
Then, we tested the hypothesis that microvascular embolization into coronary artery was associated with diastolic function, and found some relationships. But since only microvascular embolization is insufficient for elevation in diastolic stiffness, and will continue to develop this finding to experimental HFpEF model in canine.

Research Products

• [Journal Article] Ratio of pro-B-type natriuretic peptide (BNP) to total BNP is decreased in mild, but not severe, acute decompensated heart failure patients; A novel compensatory mechanism for acute heart failure. (2018)
  • Author(s): Takahama Hiroyuki、Takashio Seiji、Nishikimi Toshio、Hayashi Tomohiro、Nagai-Okatani Chiaki、Nakagawa Yasuaki、Amaki Makoto、Ohara Takahiro、Hasegawa Takuya、Sugano Yasuo、Kanzaki Hideaki、Yasuda Satoshi、Kangawa Kenji、Minamino Naoto、Anzai Toshihisa
  • Journal Title: Int J Cardiol Volume: 258 Pages: 165-171
  • DOI: 10.1016/j.ijcard.2017.12.047
  • Peer Reviewed
• [Journal Article] Use of serum fibroblast growth factor 23 vs. plasma B-type natriuretic peptide levels in assessing the pathophysiology of patients with heart failure (2017)
  • Author(s): Imazu M, Takahama H, Amaki M, Sugano Y, Ohara T, Hasegawa T, Kanzaki H, Anzai T, Mochizuki N, Asanuma H, Asakura M, Kitakaze M.
  • Journal Title: Hypertension Research Volume: 40 Pages: 181-188
  • DOI: 10.1038/hr.2016.130
  • Peer Reviewed / Open Access
• [Journal Article] Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets (2017)
  • Author(s): Takahama Hiroyuki、Kitakaze Masafumi
  • Journal Title: American Journal of Physiology-Heart and Circulatory Physiology Volume: 313
  • DOI: 10.1152/ajpheart.00215.2017
• [Presentation] Association of ratio of proBNP to total BNP with heart failure severity: A novel compensatory mechanism for acute heart failure (2018)
  • Author(s): Takahama H, et al.
  • Organizer: 日本循環器学会
• [Presentation] roBNP ratio to total BNP predicts future cardiac reverse remodeling in acute heart failure patients with reduced ejection fraction. (2018)
  • Author(s): Takahama H, et al.
  • Organizer: 日本循環器学会
• [Presentation] Is there a relationship in a molar ratio of circulating BNP molecular forms with renal function in acute heart failure patients? (2017)
  • Author(s): 高濱博幸
  • Organizer: 日本循環器学会総会
  • Place of Presentation: 金沢市
  • Year and Date: 2017-03-17
• [Presentation] Impact of continuous reduction in B-type natriuretic peptide bioactivity during hospitalization in patients with advanced heart failure (2017)
  • Author(s): Takahama H, et al.
  • Organizer: American Heart Association
  • Int'l Joint Research
• [Presentation] Molar ratio of N-terminal fragment of pro-B-type natriuretic peptide (BNP) to proBNP predicts occurrence of acute kidney injury in patients with acute heart failure (2017)
  • Author(s): Takahama H, et al.
  • Organizer: American Heart Association
  • Int'l Joint Research
• [Presentation] Time course changes in plasma levels of B-type natriuretic peptide molecular forms in acute phases in hospitalized acute decompensated heart failure patients (2015)
  • Author(s): 高濱博幸
  • Organizer: American Heart Association
  • Place of Presentation: Orland
  • Year and Date: 2015-11-07
  • Int'l Joint Research