Pathophysiological significance of the Klotho-FGF system in myocardial diseases

• Project/Area Number: 16K09429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nagoya University
• Principal Investigator: Okumura Takahiro 名古屋大学, 医学部附属病院, 病院講師 (60635598)
• Co-Investigator(Kenkyū-buntansha): 森本 竜太 名古屋大学, 医学部附属病院, 病院助教 (00755499) ; 安田 宜成 名古屋大学, 医学系研究科, 寄附講座准教授 (60432259) ; 坂東 泰子 (暮石泰子) 名古屋大学, 医学部附属病院, 講師 (60452190) ; 室原 豊明 名古屋大学, 医学系研究科, 教授 (90299503)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 拡張型心筋症 / FGF23 / 予後 / 心筋症 / リモデリング / Klotho-FGF / 心筋疾患 / Klotho-FGF系

Outline of Final Research Achievements

We examined the relationship between serum FGF-23 levels and biomarkers,　hemodynamics, and prognosis in 42 patients with dilated cardiomyopathy. FGF-23 levels in peripheral vein was negatively correlated with estimated glomerular filtration rate and positively with high-sensitivity troponin T levels. In survival analysis, the cardiac event rate was significantly higher in the High FGF-23 group than in the Low FGF-23 group. In multivariate analysis, the high FGF-23 group was an independent predictor of cardiac events. In multiple regression analysis, the estimated glomerular filtration rate and brain natriuretic peptide levels were significant determinants of FGF-23 levels. Collagen volume fraction in endomyocardial biopsy samples was not significantly correlated with peripheral FGF-23 levels, but was weakly correlated with the transcardiac gradient of FGF-23 levels defined as the difference in concentration between the coronary sinus and the base of the aorta.

Academic Significance and Societal Importance of the Research Achievements

研究代表者らは,拡張型心筋症患者における末梢血FGF-23血中濃度が推定糸球体濾過量と逆相関し,高感度トロポニンT濃度と相関することを示した。また,FGF-23高値は,不良な予後と関連し,心筋における線維化が心臓前後の血液FGF-23濃度差と相関することを明らかにした。これらの結果は,FGF-23が拡張型心筋症の心筋リモデリングおよび予後に対する新たな治療ターゲットとなりうる可能性を示しており,次世代の診断や治療法の開発,心筋症の発症・進展予防への臨床応用に展開するための基盤となりうることが示唆された。

Research Products

• [Journal Article] Spleen size improvement in advanced heart failure patients using a left ventricular assist device (2020)
  • Author(s): Hiraiwa Hiroaki、Okumura Takahiro、Sawamura Akinori、Kondo Toru、Kazama Shingo、Kimura Yuki、Shibata Naoki、Arao Yoshihito、Oishi Hideo、Kato Hiroo、Kuwayama Tasuku、Yamaguchi Shogo、Furusawa Kenji、Morimoto Ryota、Murohara Toyoaki
  • Journal Title: Artificial Organs Volume: 印刷中 Pages: 700-708
  • DOI: 10.1111/aor.13658
  • Peer Reviewed
• [Journal Article] Unsolved Issue in Left Ventricular Noncompaction: Is the Strange Form of Myocardium Congenital or Acquired? (2019)
  • Author(s): Okumura T, Murohara T.
  • Journal Title: Cardiology Volume: 143 Pages: 105-106
  • DOI: 10.1159/000501585
  • Peer Reviewed
• [Journal Article] The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy. (2018)
  • Author(s): Hiraiwa H, Okumura T, Sawamura A, Sugiura Y, Kondo T, Watanabe N, Aoki S, Ichii T, Kitagawa K, Kano N, Fukaya K, Furusawa K, Morimoto R, Takeshita K, Bando YK, Murohara T.
  • Journal Title: J Cardiol. Volume: 82 Pages: 699-707
  • DOI: 10.1016/j.jjcc.2017.09.002
  • Peer Reviewed
• [Journal Article] Corrigendum to "The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy" [J. Cardiol. 71 (2018) 284-290]. (2018)
  • Author(s): Hiraiwa H, Okumura T, Sawamura A, Sugiura Y, Kondo T, Watanabe N, Aoki S, Ichii T, Kitagawa K, Kano N, Fukaya K, Furusawa K, Morimoto R, Takeshita K, Bando YK, Murohara T.
  • Journal Title: J Cardiol. Volume: 印刷中
  • DOI: 10.1016/j.jjcc.2018.02.001
  • Peer Reviewed
• [Journal Article] Author's reply. (2018)
  • Author(s): Hiraiwa H, Okumura T, Sawamura A, Murohara T.
  • Journal Title: J Cardiol. Volume: 印刷中
  • DOI: 10.1016/j.jjcc.2018.02.005
  • Peer Reviewed
• [Journal Article] Left ventricular phase entropy: Novel prognostic predictor in patients with dilated cardiomyopathy and narrow QRS. (2017)
  • Author(s): Kano N, Okumura T, Isobe S, Sawamura A, Watanabe N, Fukaya K, Mori H, Morimoto R, Kato K, Bando YK, Murohara T.
  • Journal Title: J Nucl Cardiol Volume: 印刷中
  • DOI: 10.1007/s12350-017-0807-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Long-Term Pathological Follow-Up of Myocardium in a Carrier of Duchenne Muscular Dystrophy With Dilated Cardiomyopathy. (2017)
  • Author(s): Kondo T, Okumura T, Takefuji M, Hiraiwa H, Sugiura Y, Watanabe N, Aoki S, Ichii T, Kitagawa K, Kano N, Fukaya K, Furusawa K, Sawamura A, Morimoto R, Bando YK, Takemura G, Murohara T.
  • Journal Title: Circ Heart Fail Volume: 印刷中
  • DOI: 10.1161/circheartfailure.117.003826
  • NAID: 120006305563
  • Peer Reviewed
• [Presentation] The prognostic Impact of Fibroblast Growth Factor 23 in Ambulatory Patients with Dilated Cardiomyopathy (2019)
  • Author(s): Shingo Kazama, Takahiro Okumura, Yuki Kimura, Naoki Shibata, Yoshihito Arao, Hideo Oishi, Hiroo Kato, Tasuku Kuwayama, Shogo Yamaguchi, Toru Kondo, Hiroaki Hiraiwa, Ryota Morimoto, Toyoaki Murohara
  • Organizer: 第23回日本心不全学会学術集会
• [Presentation] 拡張型心筋症の予後予測におけるアミノ酸分析の有用性 (2019)
  • Author(s): 木村祐樹, 奥村貴裕, 風間信吾, 柴田直紀, 大石英生, 桒山輔, 荒尾嘉人, 加藤宏雄, 山口尚悟, 近藤徹, 平岩宏章, 森本竜太, 室原豊明
  • Organizer: 第5回日本心筋症研究会
• [Presentation] Tau as a predictor of cardiac events in cardiomyopathy with systolic and/or diastolic dysfunction (2018)
  • Author(s): Yokoi T, Morimoto R, Okumura T, Yamaguchi S, Kuwayama T, Hiraiwa H, Haga T, Kondo T, Sugiura Y, Watanabe N, Kano N, Sawamura A, Murohara T
  • Organizer: ESC Congress 2018
  • Int'l Joint Research
• [Presentation] Comparison with exercise capacity and hemodynamic parameters of right heart catheterization in patients with implantable left ventricular assist device (2018)
  • Author(s): Kondo T, Okumura T, Kato H, Oishi H, Arao Y, Yamaguchi S, Yokoi T, Haga T, Hiraiwa H, Sawamura A, Morimoto R, Mutsuga M, Fujimoto K, Usui A, Murohara T
  • Organizer: 第22回 日本心不全学会学術集会
• [Presentation] Relationship between the Change of Selvester QRS Score and Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy (2018)
  • Author(s): Hiroaki Hiraiwa, Takahiro Okumura, Syougo Yamaguchi, Tasuku Kuwayama, Tomoaki Haga, Tsuyoshi Yokoi, Toru Kondo, Yuki Sugiura, Naoki Watanabe, Naoaki Kano, Akinori Sawamura, Ryota Morimoto, Kyosuke Takeshita, Yasuko K. Bando, Toyoaki Murohara
  • Organizer: 第82回 日本循環器学会学術集会
• [Presentation] Early administration of mineralocorticoid receptor antagonist is useful for cardiac reverse remodeling in asymptomatic patients with dilated cardiomyopathy (2017)
  • Author(s): Takahiro Okumura, Tasuku Kuwayama, Tomoaki Haga, Hiroaki Hiraiwa, Toru Kondo, Naoki Watanabe, Naoaki Kano, Akinori Sawamura, Ryota Morimoto, Toyoaki Murohara
  • Organizer: 第21回 日本心不全学会学術集会
• [Presentation] The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy (2017)
  • Author(s): H. Hiraiwa, T. Okumura, A. Sawamura, Y. Sugiura, T. Kondo, N. Watanabe, S. Aoki, T. Ichii, N. Kano, K. Fukaya, K. Furusawa, R. Morimoto, K. Takeshita, Y. Bando, T. Murohara
  • Organizer: ESC Congress 2017
  • Int'l Joint Research
• [Presentation] 心電図で迫る心筋症診断 (2017)
  • Author(s): 奥村貴裕，澤村昭典，平岩宏章，深谷兼次，森本竜太，坂東泰子，室原豊明
  • Organizer: 第3回日本心筋症研究会
  • Place of Presentation: 長良川国際会議場 (岐阜県岐阜市)
  • Invited
• [Presentation] Impact of the Selvester QRS Score on Prognosis and Myocardial Fibrosis in Dilated Cardiomyopathy (2016)
  • Author(s): Hiroaki Hiraiwa, Takahiro Okumura, Toru Kondo, Naoki Watanabe, Naoaki Kano, Kenji Fukaya, Akinori Sawamura, Ryota Morimoto, Yasuko Bando, Toyoaki Murohara
  • Organizer: 第20回日本心不全学会学術集会
  • Place of Presentation: ロイトン札幌 (北海道札幌市)
  • Year and Date: 2016-10-07
• [Presentation] Cardiomyocyte bulking is a novel predictor of left ventricular reverse remodeling in patients with dilated cardiomyopathy (2016)
  • Author(s): Kenji Fukaya, Takahiro Okumura, Hiroaki Hiraiwa, Toru Kondo, Souichiro Aoki, Takeo Ichii, Kenji Furusawa, Naoki Watanabe, Naoaki Kano, Hiroaki Mori, Akinori Sawamura, Ryota Morimoto, Yasuko Bando, Toyoaki Murohara
  • Organizer: ESC Congress 2016
  • Place of Presentation: Fiera di Roma (Roma, Italy)
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Book] ザ・マニュアル 心不全のセット検査 (2019)
  • Author(s): 奥村貴裕
  • Total Pages: 180
  • Publisher: メジカルビュー社
  • ISBN: 9784758314480
• [Book] 循環器ジャーナル 投与中の心筋保護薬 やめたらどうなるの？ (2017)
  • Author(s): 奥村貴裕
  • Total Pages: 168
  • Publisher: 医学書院
  • ISBN: 9784260029483
• [Book] 循環器ジャーナル Clinical Scenario による急性心不全治療 (2017)
  • Author(s): 奥村貴裕，加藤真帆人，佐藤直樹，岸拓弥，佐藤幸人，南雄一郎，桃原哲也，猪又孝元，駒村和雄，廣谷信一，増山理，鈴木聡，竹石恭知，絹川弘一郎，志賀剛，坂田泰史，永井利幸，安田聡，秋山英一，木村一雄，福本義弘，山田典一，弓野大，山下武志，大西勝也，柴垣有吾，安村良男，絹川真太郎，他
  • Total Pages: 176
  • Publisher: 医学書院
• [Book] 循環器内科 二次性心筋症の臨床 (2017)
  • Author(s): 奥村貴裕，池田宇一，小林茂樹，矢崎善一，小山潤，久保亨，池田隆徳，前嶋康浩，廣野恵一，渡邉雅貴，金森寛充，神谷千津子，山口修，弓野大，他
  • Total Pages: 108
  • Publisher: 科学評論社
• [Book] 診断モダリティとしての心筋病理 (2017)
  • Author(s): 奥村貴裕，坂東泰子，室原豊明，廣江道昭，森本紳一郎，河合祥雄，和泉徹，磯部光章，猪又孝元，今中恭子，竹村元三，植田初江，尾上健児，金森寛充，齋藤恒徳，他
  • Total Pages: 214
  • Publisher: 南江堂