The effect of exercise training on the recurrence prevention in patients with takotsubo syndrome

• Project/Area Number: 18K10763
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Akashi Yoshihiro 聖マリアンナ医科大学, 医学部, 教授 (40350615)
• Co-Investigator(Kenkyū-buntansha): 鈴木 規雄 聖マリアンナ医科大学, 医学部, 助教 (00770158) ; 木田 圭亮 聖マリアンナ医科大学, 医学部, 准教授 (60465432) ; 足利 光平 聖マリアンナ医科大学, 医学部, 講師 (60645604) ; 米山 喜平 聖マリアンナ医科大学, 医学部, 講師 (70386944) ; 石橋 祐記 聖マリアンナ医科大学, 医学部, 准教授 (90410076)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: たこつぼ症候群 / 運動療法 / ストレス / たこつぼ

Outline of Final Research Achievements

Patients with Takotsubo syndrome were randomly assigned to the physical training group and the non-physical training group, and the absence of recurrence was examined as the primary endpoint. The average age of the 13 subjects was 72.0 years, and 3 of them dropped out of the test and 10 were able to participate in the exercise stress test. As a result of random allocation, the subjects were divided into two groups. At the time of participation in the study, a symptom-limited cardiopulmonary exercise test was performed, and exercise prescription was given to the physical training group at the anaerobic threshold (AT). One death from heart failure was observed in the non-exercise group, but no other recurrences were observed. It was suggested that physical training for patients with Takotsubo syndrome could prevent recurrence and have a positive effect on prognosis.

Academic Significance and Societal Importance of the Research Achievements

たこつぼ症候群は予防法も治療法も確立していない疾患群である、再発する割合は全患者のおよそ5％に及ぶ。急性冠症候群に比べると患者数が少ないため、治療法確立のための臨床試験を行うことが難しいこと、薬物による介入で心機能の回復が望めない報告が多いことより、薬に頼らない治療法および再発予防の方法として、運動療法の可能性を検討した。心臓リハビリテーションで行われている運動療法の手法を用い、たこつぼ症候群患発症後に運動療法を取り入れることで予後改善に繋がるかを検討したが、運動療法は安全に施行でき、予後改善に寄与する可能性があることは、薬に頼らない治療法として「運動」が見直されるべきである。

Research Products

• [Int'l Joint Research] University Heart Center Luebeck(ドイツ)
• [Int'l Joint Research] University Heart Center Luebeck(ドイツ)
• [Int'l Joint Research] University of Foggia(イタリア)
• [Journal Article] Epidemiology, Pathogenesis, and Clinical Course of Takotsubo Syndrome (2022)
  • Author(s): Citro Rodolfo、Radano Ilaria、Bellino Michele、Mauro Ciro、Okura Hiroyuky、Bossone Eduardo、Akashi Yoshihiro J.
  • Journal Title: Heart Failure Clinics Volume: 18 Issue: 1 Pages: 125-137
  • DOI: 10.1016/j.hfc.2021.08.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cardiac Telerehabilitation ― A Solution for Cardiovascular Care in Japan ― (2021)
  • Author(s): Kaihara Toshiki、Scherrenberg Martijn、Falter Maarten、Frederix Ines、Itoh Haruki、Makita Shigeru、Akashi Yoshihiro J.、Dendale Paul
  • Journal Title: Circulation Reports Volume: 3 Issue: 12 Pages: 733-736
  • DOI: 10.1253/circrep.CR-21-0126
  • NAID: 130008128223
  • ISSN: 2434-0790
  • Year and Date: 2021-12-10
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Myocardial Contractile Function Recovery, Systemic Inflammation, and Prognosis in Takotsubo Syndrome (2021)
  • Author(s): Yoneyama Kihei、Akashi Yoshihiro J.
  • Journal Title: Circulation Journal Volume: 85 Issue: 10 Pages: 1832-1833
  • DOI: 10.1253/circj.CJ-21-0322
  • NAID: 130008091440
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2021-09-24
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gender Differences in the Circadian and Seasonal Variations in Patients with Takotsubo Syndrome: A Multicenter Registry at Eight University Hospitals in East Japan (2021)
  • Author(s): Yoshizawa Michiko、Itoh Tomonori、Morino Yoshihiro、Taniai Seiichi、Ishibashi Yuki、Komatsu Takaaki、Taguchi Isao、Nishinari Makoto、Ako Junya、Kyono Hiroyuki、Furukawa Taiji、Murakami Tsutomu、Ikari Yuji、Kato Ritsushi、Matsumoto Kazuo、Sakuma Masashi、Sugimura Hiroyuki、J. Akashi Yoshihiro、Yoshino Hideaki
  • Journal Title: Internal Medicine Volume: 60 Issue: 17 Pages: 2749-2755
  • DOI: 10.2169/internalmedicine.6910-20
  • NAID: 130008082395
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-09-01
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of perioperative change in physical function on midterm outcomes after transcatheter aortic valve implantation (2021)
  • Author(s): Ashikaga Kohei、Doi Shunichi、Yoneyama Kihei、Watanabe Mika、Suzuki Norio、Kuwata Shingo、Kaihara Toshiki、Koga Masashi、Okuyama Kazuaki、Kamijima Ryo、Tanabe Yasuhiro、Takeichi Naoya、Watanabe Satoshi、Izumo Masaki、Kida Keisuke、Akashi Yoshihiro J.
  • Journal Title: Heart and Vessels Volume: 36 Issue: 7 Pages: 1072-1079
  • DOI: 10.1007/s00380-021-01776-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population (2021)
  • Author(s): Ashikaga Kohei、Itoh Haruki、Maeda Tomoko、Itoh Hidetaka、Ichikawa Yuri、Tanaka Shiori、Ajisaka Ryuichi、Koike Akira、Makita Shigeru、Omiya Kazuto、Kato Yuko、Adachi Hitoshi、Nagayama Masatoshi、Tajima Akihiko、Harada Naomi、Akashi Yoshihiro J
  • Journal Title: Journal of Cardiology Volume: 77 Issue: 1 Pages: 57-64
  • DOI: 10.1016/j.jjcc.2020.07.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Value of Transvalvular Flow Rate during Exercise in Asymptomatic Patients with Aortic Stenosis (2020)
  • Author(s): Hirasawa Kensuke、Izumo Masaki、Suzuki Kengo、Suzuki Tomomi、Ohara Hiroshi、Watanabe Mika、Sato Yukio、Kamijima Ryo、Nobuoka Sachihiko、Akashi Yoshihiro J.
  • Journal Title: Journal of the American Society of Echocardiography Volume: 33 Issue: 4 Pages: 438-448
  • DOI: 10.1016/j.echo.2019.11.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic value of Mini Nutritional Assessment?Short Form with aortic valve stenosis following transcatheter aortic valve implantation (2020)
  • Author(s): Doi Shunichi、Ashikaga Kohei、Kida Keisuke、Watanabe Mika、Yoneyama Kihei、Suzuki Norio、Kuwata Shingo、Kaihara Toshiki、Koga Masashi、Okuyama Kazuaki、Kamijima Ryo、Tanabe Yasuhiro、Takeichi Naoya、Watanabe Satoshi、Izumo Masaki、Ishibashi Yuki、Akashi Yoshihiro J.
  • Journal Title: ESC Heart Failure Volume: 7 Issue: 6 Pages: 4024-4031
  • DOI: 10.1002/ehf2.13007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term prognosis in patients with Takotsubo syndrome (2019)
  • Author(s): Akashi Yoshihiro J.
  • Journal Title: European Journal of Heart Failure Volume: 印刷中 Issue: 6 Pages: 790-791
  • DOI: 10.1002/ejhf.1417
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Physical performance as a predictor of midterm outcome after mitral valve surgery (2019)
  • Author(s): Ashikaga Kohei、Saji Mike、Takanashi Shuichiro、Nagayama Masatoshi、Akashi Yoshihiro J.、Isobe Mitsuaki
  • Journal Title: Heart and Vessels Volume: 34 Issue: 10 Pages: 1665-1673
  • DOI: 10.1007/s00380-019-01397-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of β Blocker Versus αβ-Blocker Treatment on Heart Rate Response During Incremental Cardiopulmonary Exercise in Japanese Male Patients with Subacute Myocardial Infarction. (2019)
  • Author(s): Nemoto S,Kasahara Y,Izawa KP,Watanabe S,Yoshizawa K,Takeichi N,Kamiya K,Suzuki N,Omiya K,Matsunaga A,Akashi YJ
  • Journal Title: International journal of environmental research and public health Volume: 16 Issue: 16 Pages: 2838-2838
  • DOI: 10.3390/ijerph16162838
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 【心不全(第2版)下-最新の基礎・臨床研究の進歩-】 心不全の原因疾患（基礎疾患）-病態, 発症機序（心不全）, 治療- 心筋疾患 たこつぼ症候群 (2019)
  • Author(s): 明石嘉浩
  • Journal Title: 日本臨床 Volume: 77 Pages: 289-296
  • Open Access
• [Journal Article] 【ICU治療指針Ⅰ】循環器疾患と管理 循環器疾患 たこつぼ症候群 (2019)
  • Author(s): 明石嘉浩
  • Journal Title: 救急・集中治療 Volume: 31 Pages: 657-661
  • Open Access
• [Journal Article] 【循環器症候群(第3版)-その他の循環器疾患を含めて-】心筋疾患 たこつぼ症候群 (2019)
  • Author(s): 明石嘉浩
  • Journal Title: 日本臨床 Volume: 別冊循環器症候群I Pages: 230-235
  • Open Access
• [Journal Article] Takotsubo syndrome: State-of-the-art review by an expert panel - Part 1 (2019)
  • Author(s): Dias A, Nunez Gil IJ, Santoro F, Madias JE, Pelliccia F, Brunetti ND, Salmoirago-Blotcher E, Sharkey SW, Eitel I, Akashi YJ, et. al.
  • Journal Title: Cardiovascular Revascularization Medicine Volume: 20 Issue: 1 Pages: 70-79
  • DOI: 10.1016/j.carrev.2018.11.015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Takotsubo syndrome: State-of-the-art review by an expert panel - Part 2 (2019)
  • Author(s): Dias A, Nunez Gil IJ, Santoro F, Madias JE, Pelliccia F, Brunetti ND, Salmoirago-Blotcher E, Sharkey SW, Eitel I, Akashi YJ, et. al.
  • Journal Title: Cardiovascular Revascularization Medicine Volume: 20 Issue: 2 Pages: 153-166
  • DOI: 10.1016/j.carrev.2018.11.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology (2018)
  • Author(s): Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, et al.
  • Journal Title: European Heart Journal Volume: 39 Issue: 22 Pages: 2032-2046
  • DOI: 10.1093/eurheartj/ehy076
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management (2018)
  • Author(s): Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, et al.
  • Journal Title: European Heart Journal Volume: 39 Issue: 22 Pages: 2047-2062
  • DOI: 10.1093/eurheartj/ehy077
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Clinical and Mechanistic Aspects in takotsubo syndrome (2020)
  • Author(s): Yoshihiro J. Akashi
  • Organizer: European Society of Cardiology Congress 2020
  • Int'l Joint Research / Invited
• [Presentation] Takotsubo Syndrome: Predisposition and Risk Factors (2020)
  • Author(s): 明石嘉浩
  • Organizer: 第84回 日本循環器学会学術集会
  • Int'l Joint Research / Invited
• [Presentation] Role of Arrhythmias (2019)
  • Author(s): Yoshihiro Akashi
  • Organizer: Heart Failure 2019, Athens, Greece
  • Int'l Joint Research / Invited
• [Presentation] たこつぼ症候群におけるパラダイムシフト (2019)
  • Author(s): 明石嘉浩
  • Organizer: 第66回日本不整脈心電学会学術大会
• [Presentation] ST上昇型と非ST上昇型たこつぼ症候群の臨床的特徴と院内予後-8大学循環器研究会他施設共同研究- (2019)
  • Author(s): Koeda Yorihiko, Itoh Tomonori, Morino Yoshihiro, Taguchi Isao, Ako Junya, Furukawa Taiji, Ikari Yuji, Matsumoto Kazuo, Sakuma Masashi, Sugimura Hiroyuki, Akashi Yoshihiro, Yoshino Hideaki
  • Organizer: 第56回日本臨床生理学会総会
  • Int'l Joint Research
• [Presentation] たこつぼ心筋症におけるパラダイムシフト (2018)
  • Author(s): 明石嘉浩
  • Organizer: 第22回日本心不全学会
  • Invited
• [Presentation] タコつぼ型心筋障害 (2018)
  • Author(s): 明石嘉浩
  • Organizer: 日本心エコー図学会 第15回秋期講習会
  • Invited
• [Presentation] Takotsubo Cardiomyopathy (2018)
  • Author(s): Yoshihiro J. Akashi
  • Organizer: 23rd Annual Scientific Meeting of the International Society of Cardiovascular Pharmacology
  • Int'l Joint Research / Invited
• [Book] たこつぼ症候群 (2021)
  • Author(s): 明石嘉浩
  • Total Pages: 242
  • Publisher: 克誠堂出版
• [Book] 循環器診療コンプリート 心筋症 (2021)
  • Author(s): 明石嘉浩
  • Total Pages: 272
  • Publisher: 学研メディカル秀潤社
  • ISBN: 9784780904079
• [Book] 今日の治療指針 2021年版［デスク判］ (2021)
  • Author(s): 明石嘉浩
  • Total Pages: 2151
  • Publisher: 医学書院
  • ISBN: 9784260042826
• [Book] 欧州心臓病学会（ESC)心血管ハンドブック日本語翻訳版 (2020)
  • Author(s): 明石嘉浩
  • Total Pages: 929
  • Publisher: Oxford University Press
• [Book] 循環器疾患最新の治療2020-2021 (2020)
  • Author(s): 足利光平、明石嘉浩
  • Total Pages: 500
  • Publisher: 南江堂
  • ISBN: 9784524249763
• [Book] 急性循環不全 (2019)
  • Author(s): 明石嘉浩
  • Total Pages: 344
  • Publisher: 中山書店
  • ISBN: 9784521743356