Multiple biomarkers in patients with chronic circuratory failure and multiorgan dysfunction

• Project/Area Number: 16K09414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Tohoku University
• Principal Investigator: Tatebe Shunsuke 東北大学, 大学病院, 助教 (90456062)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: バイオマーカー / 成人先天性心疾患 / 慢性心不全 / 心血管予後 / HCV / MELD-XI / PR間隔 / Cyclophilin A / 多臓器連関 / 慢性血栓塞栓性肺高血圧症 / 冠動脈疾患 / 予後 / マルチバイオマーカー / 血行動態 / 肺循環障害 / 先天性心疾患 / 慢性循環不全 / 多臓器障害

Outline of Final Research Achievements

The purpose of the present study was to evaluate multiple organ dysfunction and prognosis by multiple biomarkers and invasive hemodynamic methods in patients with chronic circulatory failure. We have reported plasma levels of cyclophilin A (CyPA) predicted cardiovascular prognosis in patients with coronary artery disease (CAD). We have also found that plasma CyPA as a useful biomarker for evaluation of the effects of balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. In the field of adult congenital heart disease (ACHD), we have reported (1) hepatitis C virus positivity adversely impacted cardiac function and long-term prognosis in patients undergoing heart surgery before 1992 and (2) ACHD patients with high MELD-XI (Model for End-Stage Liver Disease Excluding INR) score had poor cardiovascular outcomes, and (3) PR interval prolongation predicted cardiovascular prognosis in adults with repaired tetralogy of Fallot.

Academic Significance and Societal Importance of the Research Achievements

慢性循環不全患者の遠隔期心血管合併症発症のリスク因子を後向き、前向き研究において複数同定した。各々の心疾患において、当該リスク因子を予後バイオマーカーとして計測・評価することで、ハイリスク患者の同定および患者予後の改善が期待される。さらに本研究は当該疾患の、診療ガイドライン策定にも資する臨床的エビデンスを提供した。新たな介入研究の標的候補としても、役立つものとおもわれる。

Research Products

• [Journal Article] Prognostic Significance of PR Interval Prolongation in Adult Patients With Total Correction of Tetralogy of Fallot (2018)
  • Author(s): Kimura Yoshitaka、Fukuda Koji、Nakano Makoto、Hasebe Yuhi、Fukasawa Kyoshiro、Chiba Takahiko、Miki Keita、Tatebe Shunsuke、Miyata Satoshi、Ota Hideki、Kimura Masato、Adachi Osamu、Saiki Yoshikatsu、Shimokawa Hiroaki
  • Journal Title: Circulation: Arrhythmia and Electrophysiology Volume: 11 Issue: 11 Pages: 1-11
  • DOI: 10.1161/circep.118.006234
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Hepatitis C Virus Antibody-Positivity on Cardiac Function and Long-Term Prognosis in Patients With Adult Congenital Heart Disease (2018)
  • Author(s): Konno Ryo、Tatebe Shunsuke、Sugimura Koichiro、Satoh Kimio、Aoki Tatsuo、Miura Masanobu、Yamamoto Saori、Sato Haruka、Kozu Katsuya、Terui Yosuke、Miyata Satoshi、Adachi Osamu、Kimura Masato、Saiki Yoshikatsu、Shimokawa Hiroaki
  • Journal Title: The American Journal of Cardiology Volume: 122 Issue: 11 Pages: 1965-1971
  • DOI: 10.1016/j.amjcard.2018.08.045
  • Peer Reviewed / Open Access
• [Journal Article] Sex differences in hemodynamic responses and long-term survival to optimal medical therapy in patients with pulmonary arterial hypertension. (2018)
  • Author(s): Kozu K, Sugimura K, Aoki T, Tatebe S, Yamamoto S, Yaoita N, Shimizu T, Nochioka K, Sato H, Konno R, Satoh K, Miyata S, Shimokawa H.
  • Journal Title: Heart Vessels. Volume: in press Issue: 8 Pages: 939-947
  • DOI: 10.1007/s00380-018-1140-6
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic impacts of plasma levels of cyclophilin A in patients with coronary artery disease. (2017)
  • Author(s): Ohtsuki T, Satoh K, Omura J, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Sunamura S, Yaoita N, Aoki T, Tatebe S, Sugimura K, Takahashi J, Miyata S, Shimokawa H.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 37 Issue: 4 Pages: 685-693
  • DOI: 10.1161/atvbaha.116.308986
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] MELD-XI (Model for End-Stage Liver Disease Excluding INR) Score Predicts Cardiovascular Outcomes in Patients with Adults with Congenital Heart Disease (2019)
  • Author(s): Ryo Konno, Shunsuke Tatebe, Koichiro Sugimura, Kimio Satoh, Tatsuo Aoki, Masanobu Miura, Hideaki Suzuki, Saori Yamamoto, Haruka Sato, Yosuke Terui, Osamu Adachi, Masato Kimura, Yoshikatsu Saiki, Hiroaki Shimokawa
  • Organizer: 第83回日本循環器学会
• [Presentation] Factors Influencing Health-related Quality of Life in Patients with Adult Congenital Heart Disease -A Nationwide Study Supported by AMED- (2019)
  • Author(s): Shunsuke Tatebe, Yasuhiko Sakata, Koichiro Sugimura, Kimio Satoh, Takashi Shiroto, Ryo Konno, Satoshi Miyata, Osamu Adachi, Masato Kimura, Yoshiko Mizuno, Junko Enomoto, Shigeru Tateno, Hiromichi Nakajima, Kotaro Oyama, Yoshikatsu Saiki, Hiroaki Shimokawa
  • Organizer: 第83回日本循環器学会
• [Presentation] Quality of Life in Adult Patients with A Fontan Circulation -A Nationwide Study Supported by AMED- (2019)
  • Author(s): Shunsuke Tatebe, Ryo Konno, Yasuhiko Sakata, Koichiro Sugimura, Kimio Satoh, Takashi Shiroto, Satoshi Miyata, Osamu Adachi, Masato Kimura, Yoshiko Mizuno, Junko Enomoto, Shigeru Tateno, Hiromichi Nakajima, Kotaro Oyama, Yoshikatsu Saiki, Hiroaki Shimokawa
  • Organizer: 第83回日本循環器学会
• [Presentation] Prognostic Utility of Model for End-Stage Liver Disease Excluding INR (MELD-XI) Score in Patients with Adult Congenital Heart Disease (2019)
  • Author(s): Ryo Konno, Shunsuke Tatebe, Koichiro Sugimura, Kimio Satoh, Tatsuo Aoki, Masanobu Miura, Hideaki Suzuki, Saori Yamamoto, Haruka Sato, Yosuke Terui, Osamu Adachi, Masato Kimura, Yoshikatsu Saiki, Hiroaki Shimokawa
  • Organizer: 第21回日本成人先天性心疾患学会
• [Presentation] Prognostic value of model for end-stage liver disease excluding INR (MELD-XI) score in patients with adult congenital heart disease (2018)
  • Author(s): Konno R, Tatebe S, Sugimura K, Satoh K, Aoki T, Miura M, Yamamoto S, Sato H, Terui Y, Adachi O, Kimura M, Saiki Y, Shimokawa H.
  • Organizer: アメリカ心臓病学会
  • Int'l Joint Research
• [Presentation] Hepatitis C virus positivity adversely affects systemic ventricular function and long-term prognosis in patients with adult congenital heart disease (2018)
  • Author(s): 35.Konno R, Tatebe S, Sugimura K, Satoh K, Aoki T, Yamamoto S, Sato H, Kozu K, Adachi O, Kimura M, Saiki Y, Shimokawa H.
  • Organizer: ヨーロッパ心臓病学会
  • Int'l Joint Research
• [Presentation] Sex Differences in Pulmonary Arterial Hypertension in Patients with Adult Congenital Heart Disease -A Nationwide Collaborative Study- (2018)
  • Author(s): Ryo Konno, Shunsuke Tatebe, Yasuhiko Sakata, Koichiro Sugimura, Kimio Satoh, Takashi Shiroto, Osamu Adachi, Masato Kimura, Shigeru Tateno, Hiromichi Nakajima, Kotaro Oyama, Yoshikatsu Saiki, Hiroaki Shimokawa
  • Organizer: アメリカ胸部学会
  • Int'l Joint Research
• [Presentation] Important Prognostic Impacts of Serum Levels of Adipsin in Patients with Coronary Artery Disease (2018)
  • Author(s): Tomohiro Otsuki、Kimio Satoh、Toru Shimizu、 Shohei Ikeda、Nobuhiro Yaoita、Taiju Sato、Junichi Omura、Nobuhiro Kikuchi、Ryo Kurosawa、 Sinichiro Sunamura、Masamichi Nogi、Koichiro Sugimura、Tatsuo Aoki、Shunsuke Tatebe、Kotaro Nochioka、Saori Yamamoto、Jun Takahashi、Satoshi Miyata、Hiroaki Shimokawa
  • Organizer: the 82nd Annual Scientific Meeting of the Japanese Circulation Society
• [Presentation] Plasma Levels of Cyclophilin Plasma Levels of Cyclophilin A Plasma Levels of Cyclophilin A Are Associated with Increased Mortality in Patients with Heart Failure (2017)
  • Author(s): Ohtsuki T, Satoh K, Omura J, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Sunamura S, Yaoita N, Aoki T, Tatebe S, Sugimura K, Takahashi J, Miyata S, Shimokawa H.
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢市ホテル金沢
  • Year and Date: 2017-03-17
• [Presentation] Clinical Characteristics of Adult Congenital Heart Disease in a Prospective Multicenter Cohort Study -An Initial Report from the CHART-2 Study- (2017)
  • Author(s): Tatebe S, Sugimura K, Satoh K, Shimokawa H, et al.
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢市金沢フォーラス
  • Year and Date: 2017-03-17
• [Presentation] Prospective Multicenter Cohort Study for Clinical Characteristics and Cardiovascular Events of Patients with Adult Congenital Heart Disease -An Initial Report from the CHART-2 Study- (2017)
  • Author(s): Tatebe S, Sugimura K, Satoh K, Shimokawa H, et al.
  • Organizer: 第19回日本成人先天性心疾患学術集会
  • Place of Presentation: 三重県津市グリーンパーク津
  • Year and Date: 2017-01-13
• [Presentation] Adverse Effect of Hepatitis C Virus Positivity on Cardiac Function and Long-term Prognosis in Patients With Adult Congenital Heart Disease (2017)
  • Author(s): Ryo Konno, Shunsuke Tatebe, Koichiro Sugimura, Kimio Satoh, Tatsuo Aoki, Saori Yamamoto, Toru Shimizu, Haruka Sato, Katsuya Kozu, Osamu Adachi, Masato Kimura, Yoshikatsu Saiki, Hiroaki Shimokawa
  • Organizer: American Heart Association’s Scientific Sessions 2017
  • Int'l Joint Research
• [Presentation] Plasma Cyclophilin A as a Useful Biomarker for Evaluation of the Effects of Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension (2017)
  • Author(s): Katsuya Kozu, Kimio Satoh, Toru Shimizu, Tatsuo Aoki, Shunsuke Tatebe, Saori Yamamoto, Haruka Sato, Tomohiro Ohtsuki, Ryo Konno, Satoshi Miyata, Koichiro Sugimura, Hiroaki Shimokawa
  • Organizer: American Heart Association’s Scientific Sessions 2017
  • Int'l Joint Research