Risk stratification in heart failure patients using serum microRNA and echocardiography

• Project/Area Number: 16K09454
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Juntendo University
• Principal Investigator: Kato Tomoko S. 順天堂大学, 医学部, 非常勤講師 (30450886)
• Co-Investigator(Kenkyū-buntansha): 黒田 揮志夫 順天堂大学, 医学部, 助手 (10772808) ; 吉澤 佐恵子 東京女子医科大学, 医学部, 助教 (40581707) ; 天野 篤 順天堂大学, 医学部, 教授 (70338440) ; 宇都 健太 東京女子医科大学, 医学部, 助教 (80318071)
• Project Period (FY): 2016-04-01 – 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 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 循環器内科学 / 心不全 / バイオマーカー / 画像診断 / マイクロRNA / 心筋病理 / リスク層別化 / miRNA / バイマーカー / 一次予防 / 二次予防 / 心筋障害 / 予後予測 / microRNA / 発症予測 / micro RNA / 心臓超音波 / 循環器・高血圧 / アルゴリズム / 臨床 / 解析・評価

Outline of Final Research Achievements

The number of patients with heart failure has been increasing worldwide. Establishment of a risk stratification model to predict heart failure development for asymptomatic patients with cardiovascular diseases is highly expected. We analyzed mRNA expression of myocardium and serum biomarker in patients undergoing cardiac surgery. Echocardiography-derived strain analysis was used to detect asymptomatic patients with impaired myocardial functional reserve. We successfully detected 3 types of microRNA associated with fibrosis and Ca2+ handling protein. Besides, using the myocardium obtained from patients undergoing bioprosthetic valve replacement, we found the a residual immunogeneity revealed by a-Gal positivity in the valves which may cause pathological inflammation and the result of xenograft rejection. Our findings may be useful to elucidate the mechanism of heart failure development in asymptomatic patients and the role of miRNAs as heart failure biomarkers.

Academic Significance and Societal Importance of the Research Achievements

心不全患者においてmiRNAが病勢を反映する有用なバイオマーカーとして注目されているが、心機能が正常な患者において心筋予備能と照らした研究は未だない。また、心筋組織の病理解析や蛋白発現と比較した報告はない。我々は、はじめて 潜在性心予備能低下患者において、心筋線維化やＣａ調節蛋白に関与する可能性のある miRNA の変動を確認することに成功した。副次的な検討として、生体弁手術後の患者の心筋炎症が免疫反応であることも見いだした。我々の研究は、心不全の病因解明や、新たな薬物治療ターゲットの同定を可能とする成果と考える。

Research Products

• [Int'l Joint Research] Penn State Health/Columbia University/UCLA Medical Center(米国)
• [Int'l Joint Research] Jena University(ドイツ)
• [Int'l Joint Research] University of California Los Angeles/Penn State Health Medical Center/Columbia University(米国)
• [Int'l Joint Research] Jena University(ドイツ)
• [Int'l Joint Research] University of California Los Angeles/Drexel University/Columbia University(米国)
• [Int'l Joint Research] University klinikum Jena(ドイツ)
• [Int'l Joint Research]
• [Journal Article] An Autopsy Case of Cardiac Amyloidosis with Heterogeneous Deposition of Amyloid Protein: A Possible Mechanism for Relative Apical Sparing of Longitudinal Strain (2020)
  • Author(s): Sawada Naoko、Daimon Masao、Abe Hiroyuki、Ushiku Tetsuo、Kato Tomoko S.、Morita Hiroyuki、Komuro Issei
  • Journal Title: CASE Volume: 4 Issue: 2 Pages: 54-56
  • DOI: 10.1016/j.case.2019.09.009
  • Peer Reviewed / Open Access
• [Journal Article] Transthyretin Stabilizer Is Associated With Expanding Apical Sparing Area and Improving Global Cardiac Function in a Patient With Wild-Type Cardiac Amyloidosis (2019)
  • Author(s): Kato T, Ikeda N, Maurer MS, Ando Y, Tanno K.
  • Journal Title: Circulation Journal Volume: 83 Issue: 3 Pages: 690
  • DOI: 10.1253/circj.CJ-18-0612
  • NAID: 130007604106
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-02-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Use of Cardiac Imaging to Evaluate Cardiac Function and Pulmonary Hemodynamics in Patients with Heart Failure (2019)
  • Author(s): Kato Tomoko S.、Daimon Masao、Satoh Toru
  • Journal Title: Current Cardiology Reports Volume: 21 Issue: 6 Pages: 53-53
  • DOI: 10.1007/s11886-019-1138-4
  • Peer Reviewed
• [Journal Article] The Significance of the Effect of Visceral Adiposity on Left Ventricular Diastolic Function in the General Population (2019)
  • Author(s): Sawada Naoko、Daimon Masao、Kawata Takayuki、Nakao Tomoko、Kimura Koichi、Nakanishi Koki、Kurano Makoto、Hirokawa Megumi、Xu Boqing、Yamanaka Yuko、Kato Tomoko S.、Watanabe Masafumi、Yatomi Yutaka、Komuro Issei
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 4435-4435
  • DOI: 10.1038/s41598-018-37137-x
  • Peer Reviewed / Open Access
• [Journal Article] Echocardiographic assessment of right ventricular function in routine practice: Which parameters are useful to predict one-year outcome in advanced heart failure patients with dilated cardiomyopathy? (2017)
  • Author(s): Takayuki Kawata, Masao Daimon, Koichi Kimura, Tomoko Nakao, Seitetsu L. Lee, Megumi Hirokawa, Tomoko S. Kato, Masafumi Watanabe, Yutaka Yatomi, Issei Komuro
  • Journal Title: Journal of Cardiology Volume: 印刷中 Issue: 4 Pages: 316-322
  • DOI: 10.1016/j.jjcc.2017.02.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Periodontitis and bone metabolism in patients with advanced heart failure and after heart transplantation. (2017)
  • Author(s): Schulze-Spate U, Mizani I, Salaverry KR, Chang J, Wu C, Jones M, Kennel PJ, Brunjes DL, Choo TH, Kato TS, Mancini D, Grbic J, Schulze PC.
  • Journal Title: ESC Heart Fail Volume: 4 Issue: 2 Pages: 169-177
  • DOI: 10.1002/ehf2.12126
  • Int'l Joint Research
• [Journal Article] Reconsideration of Inferior Vena Cava Parameters for Estimating Right Atrial Pressure in an East Asian Population ― Comparative Simultaneous Ultrasound-Catheterization Study ― (2017)
  • Author(s): Takayuki Kawata, Masao Daimon, Seitetsu L. Lee, Koichi Kimura, Naoko Sawada, Shuo-Ju Chiang, Keitaro Mahara, Takeshi Okubo, Tomoko Nakao, Megumi Hirokawa, Boqing Xu, Tomoko S. Kato, Masafumi Watanabe, Yutaka Yatomi, Issei Komuro
  • Journal Title: Circulation Journal Volume: 81 Issue: 3 Pages: 346-352
  • DOI: 10.1253/circj.CJ-16-0916
  • NAID: 130005242992
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The impact of surgical left atrial appendage amputation/ligation on stroke prevention in patients undergoing off-pump coronary artery bypass grafting. (2017)
  • Author(s): Endo D, Kato TS, Iwamura T, Oishi A, Yokoyama Y, Kuwaki K, Inaba H, Amano A.
  • Journal Title: Heart Vessels. Volume: 32 Issue: 6 Pages: 726-734
  • DOI: 10.1007/s00380-016-0915-x
• [Journal Article] The impact of surgical left atrial appendage amputation/ligation on stroke prevention in patients undergoing off-pump coronary artery bypass grafting. (2017)
  • Author(s): Endo D, Kato TS, Iwamura T, Oishi A, Yokoyama Y, Kuwaki K, Inaba H, Amano A
  • Journal Title: Heart Vessels. Volume: 印刷中
  • Peer Reviewed
• [Presentation] Multiple micro-neo-vessels detected by optical coherence tomography (OCT) can predict a progression of cardiac allograft vasculopathy in a 15-year post transplant recipient. (2019)
  • Author(s): K. Shibata, T. S. Kato, T. Nishikura, N. Ikeda, C. Sato, K. Wakabayashi, K.Tanno.
  • Organizer: International Society for Heart and Lung Transplantation, Scientific Session 2019
  • Int'l Joint Research
• [Presentation] Ablation Of Atrial Fibrillation Improves Left Ventricular Diastolic Function And Prevents HFpEFrelated Hospitalization In Super-elderly Patients. (2019)
  • Author(s): Ikeda N, Kato TS, Fukuoka H, Wakabayashi K, Tanno K.
  • Organizer: American Heart Association, Scientific Session 2019
  • Int'l Joint Research
• [Presentation] Multiple Micro-Neo-Vessels Detected by Optical Coherence Tomography Can Predict Progression of Cardiac Allograft Vasculopathy in a 15-Year Post Transplant Recipient (2019)
  • Author(s): Shibata K, Kato TS
  • Organizer: International Society for Heart and Lung Transplantation
  • Int'l Joint Research
• [Presentation] Heart Failure and Transplant Medicine, Discussant (2019)
  • Author(s): Kato TS
  • Organizer: ISHLT 39th Annual Meeting and Scientific Sessions
  • Int'l Joint Research
• [Presentation] タファミジス投与および心房細動治療により、相対的心尖部壁運動温存領域の拡大を認めた心アミロイドーシスの一例 (2018)
  • Author(s): 池田 尚子, 加藤 倫子, 古屋 貴宏, 佐藤 千聡, 若林 公平, 丹野 郁
  • Organizer: 第66回 日本心臓病学会学術集会
• [Presentation] 大動脈弁置換術後の呼吸苦原因精査に運動負荷エコー検査が有用であったSLEの1例 膠原病合併運動誘発性肺高血圧症の検討 (2018)
  • Author(s): 池田 尚子, 加藤 倫子, 古屋 貴宏, 佐藤 千聡, 若林 公平, 丹野 郁
  • Organizer: 第66回 日本心臓病学会学術集会
• [Presentation] 後期・超高齢者の心房細動治療 ー 80歳以上の高齢者に対する心房細動治療が左室拡張機能改善に与える影響 (2018)
  • Author(s): 池田 尚子, 加藤 倫子, 丹野 郁
  • Organizer: 第66回 日本心臓病学会学術集会
• [Presentation] 非虚血性拡張型心筋症の左室の逆リモデリングと関連する臨床的因子 (2018)
  • Author(s): 石渡 惇平, 川田 貴之, 大門 雅夫, 木村 公一, 中尾 倫子, 廣川 愛美, 澤田 直子, 徐 博卿, 桐山 皓行, Munkhtuul Purevsuren, 網谷 英介, 波多野 将, 加藤 倫子, 渡辺 昌文, 小室 一成
  • Organizer: 第82回 日本循環器学会学術集会
• [Presentation] Basic Science and Translational Research, Poster Discussant (2018)
  • Author(s): Kato TS
  • Organizer: ISHLT 38th Annual Meeting and Scientific Sessions
  • Int'l Joint Research
• [Presentation] Left ventricular and atrial strain can predict development of arrhythmias in patients with Non-obstructive hypertrophic cardiomyopathy. (2016)
  • Author(s): Kattel K, Kato TS, Ichihara R, Miyazaki S, Kasai T, Diada H.
  • Organizer: 88th Science Sessions, American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] The role of echocardiography in the management of patients undergoing ventricular assist device implantation and/or transplantation. (2016)
  • Author(s): Kato TS
  • Organizer: International Academy of Cardiology Annual Scientific Sessions 2016, . 21st World Congress on Heart Disease
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-07-30
  • Int'l Joint Research / Invited