Exercise training for vasospastic angina

• Project/Area Number: 19K11762
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: International University of Health and Welfare (2020-2021); Tohoku University (2019)
• Principal Investigator: Matsumoto Yasuharu 国際医療福祉大学, 国際医療福祉大学塩谷病院, 教授 (90600528)
• Project Period (FY): 2019-04-01 – 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 運動療法 / 狭心症 / 冠攣縮 / CT / 運動耐容能 / 冠微小血管障害 / 心臓リハビリ / 心臓リハビリテーション / 冠動脈攣縮

Outline of Research at the Start

近年、虚血性心臓病の頻度や医療費は増加し、特に冠動脈に過剰な収縮反応を来たし、胸痛 や突然死を引き起こす冠攣縮性狭心症は、近年、日本のみならず欧州でも多いと報告される。 薬剤抵抗生の難治性冠攣縮も問題である。しかし、冠攣縮性狭心症に対する運動療法(心臓 リハビリテーション)の有効性や機序は不明である。我々は、冠攣縮の病態形成に、冠動脈 外膜の炎症や血管平滑筋細胞の過収縮分子機構 (Rhoキナーゼ活性化)が重要であることを、 動物実験から臨床研究にて明らかに
してきた。本研究の目的は、冠攣縮 性狭心症に対する運動療法・心臓リハの有効性を検討し、その細胞・分子機構を明らかにすることである。

Outline of Final Research Achievements

We aimed to examine whether vasodilator capacity of coronary microvessels is impaired in VSA patients, and if so, whether exercise exerts beneficial effects on the top of CCBs. In the former protocol, myocardial blood flow(MBF) on CT perfusion was significantly decreased in the VSA group compared with the Non-VSA group. In the latter protocol, exercise capacity was significantly increased in the Exercise group than in the Non-Exercise group. MBF was also significantly improved after 3 months only in the Exercise group, although there were no significant between-group differences. These results provide the first evidence that, in VSA patients, exercise training on the top of CCBs treatment may be useful to improve physical performance, although its effect on MBF may be minimal.

Academic Significance and Societal Importance of the Research Achievements

我々は、冠攣縮性狭心症の病態において、冠動脈の外膜側の炎症が重要な役割を担うことを明らかにしてきた。
冠攣縮性狭心症にしばしば合併する冠微小循環障害を改善しうる定期的運動療法の検討は国内・国外含めて報告がなく、オンリーワンの研究である。本研究結果により、日本や欧米で近年増加している虚血性心臓病の主因の一つである冠攣縮に対する運動生理学的病態の更なる理解および患者の生活の質の向上に大きく寄与しうることが期待される。

Research Products

• [Journal Article] Beneficial effects of exercise training on physical performance in patients with vasospastic angina (2021)
  • Author(s): Sugisawa J, Matsumoto Y, Takeuchi M, Suda A, Tsuchiya S, Ohyama K, Nishimiya K, Akizuki M, Sato K, Ohura S, Ota H, Ikeda S, Shindo T, Kikuchi Y, Hao K, Shiroto T, Takahashi J, Miyata S, Sakata Y, Takase K, Kohzuki M, Shimokawa H.
  • Journal Title: Int J Cardiol Volume: 328 Pages: 14-21
  • Peer Reviewed
• [Journal Article] Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo. (2021)
  • Author(s): Watanabe T, Matsumoto Y, Nishimiya K, Shindo T, Amamizu H, Sugisawa J, Tsuchiya S, Sato K, Morosawa S, Ohyama K, Watanabe-Asaka T, Hayashi M, Kawai Y, Takahashi J, Yasuda S, Shimokawa H.
  • Journal Title: PLoS One. Volume: 16 Issue: 9 Pages: e0257175-e0257175
  • DOI: 10.1371/journal.pone.0257175
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic Performance of Dynamic Myocardial Perfusion Imaging Using Dual-Source Computed Tomography (2021)
  • Author(s): Kitagawa K, Nakamura S, Ota H, Ogawa R, Shizuka T, Kubo T, Yi Y, Ito T, Nagasawa N, Omori T, Nakamori S, Kurita T, Sugisawa J, Hatori N, Nakashima H, Wang Y, Kido T, Watanabe K, Matsumoto Y, Dohi K, Sakuma H.
  • Journal Title: J Am Coll Cardiol Volume: 78 Pages: 1937-1949
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic Impacts of Comorbid Significant Coronary Stenosis and Coronary Artery Spasm in Patients With Stable Coronary Artery Disease (2021)
  • Author(s): Hao Kiyotaka、Takahashi Jun、Kikuchi Yoku、Suda Akira、Sato Koichi、Sugisawa Jun、Tsuchiya Satoshi、Shindo Tomohiko、Nishimiya Kensuke、Ikeda Shohei、Tsuburaya Ryuji、Shiroto Takashi、Matsumoto Yasuharu、Miyata Satoshi、Sakata Yasuhiko、Yasuda Satoshi、Shimokawa Hiroaki
  • Journal Title: Journal of the American Heart Association Volume: 10 Issue: 2
  • DOI: 10.1161/jaha.120.017831
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic Links Between OCT-Delineated Coronary Morphologies and Coronary Functional Abnormalities in Patients With INOCA. (2021)
  • Author(s): Nishimiya K, Suda A, Fukui K, Hao K, Takahashi J, Matsumoto Y, Mitsuishi K, Watanabe T, Ohyama K, Sugisawa J, Tsuchiya S, Satoh K, Shindo T, Godo S, Kikuchi Y, Shiroto T, Yasuda S, Shimokawa H.
  • Journal Title: JACC Cardiovasc Interv. Volume: 14 Pages: 606-618
  • Peer Reviewed
• [Journal Article] Treadmill exercise prevents reduction of bone mineral density after myocardial infarction in apolipoprotein E-deficient mice. (2020)
  • Author(s): Kanazawa M, Matsumoto Y, Takahashi K, Suzuki H, Uzuka H, Nishimiya K, Shimokawa H.
  • Journal Title: Eur J Prev Cardiol. Volume: 27 Pages: 28-35
  • Peer Reviewed / Open Access
• [Journal Article] Recent Advances in Vascular Imaging. (2020)
  • Author(s): Nishimiya K, Matsumoto Y, Shimokawa H.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 40
  • Peer Reviewed / Open Access
• [Journal Article] Transcatheter aortic valve implantation and cognitive function in elderly patients with severe aortic stenosis. (2020)
  • Author(s): Tsuchiya S, Matsumoto Y, Suzuki H, Takanami K, Kikuchi Y, Takahashi J, Miyata S, Tomita N, Kumagai K, Taki Y, Saiki Y, Arai H, Shimokawa H.
  • Journal Title: EuroIntervention. Volume: 15
  • Peer Reviewed / Open Access
• [Journal Article] Disappearance of Angiodysplasia Following Transcatheter Aortic Valve Implantation in a Patient with Heyde's Syndrome: A Case Report and Review of the Literature. (2020)
  • Author(s): Tsuchiya S, Matsumoto Y, Doman T, Fujiya T, Sugisawa J, Suda A, Sato K, Ikeda S, Shindo T, Kikuchi Y, Hao K, Takahashi J, Hatta W, Koike T, Masamune A, Saiki Y, Horiuchi H, Shimokawa H.
  • Journal Title: J Atheroscler Thromb. Volume: 27 Pages: 271-277
  • NAID: 130007804192
  • Peer Reviewed / Open Access
• [Journal Article] Impacts of hippocampal blood flow on changes in left ventricular wall thickness in patients with chronic heart failure. (2020)
  • Author(s): Suzuki H, Matsumoto Y, Sugimura K, Takahashi J, Miyata S, Fukumoto Y, Taki Y, Shimokawa H.
  • Journal Title: Int J Cardiol. Volume: 310 Pages: 103-107
  • Peer Reviewed / Open Access
• [Journal Article] Clinical implication of myocardial FDG uptake pattern in oncologic PET: retrospective comparison study with stress myocardial perfusion imaging as the reference standard. (2020)
  • Author(s): Takanami K, Saito M, Matsumoto Y, Sugimura K, Takase K.
  • Journal Title: Ann Nucl Med. Volume: 34 Pages: 233-243
  • Peer Reviewed / Open Access
• [Journal Article] Treadmill exercise prevents reduction of bone mineral density after myocardial infarction in apolipoprotein E-deficient mice. (2020)
  • Author(s): Kanazawa M, Matsumoto Y, Takahashi K, Suzuki H, Uzuka H, Nishimiya K, Shimokawa H.
  • Journal Title: Eur J Prevent Cardiol. Volume: 1 Pages: 28-35
  • Peer Reviewed / Open Access
• [Journal Article] Marked Impairment of Endothelium-Dependent Digital Vasodilatations in Patients With Microvascular Angina: Evidence for Systemic Small Artery Disease. (2020)
  • Author(s): Ohura-Kajitani S, Shiroto T, Godo S, Ikumi Y, Ito A, Tanaka S, Sato K, Sugisawa J, Tsuchiya S, Suda A, Shindo T, Ikeda S, Hao K, Kikuchi Y, Nochioka K, Matsumoto Y, Takahashi J, Miyata S, Shimokawa H.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 40 Pages: 1400-1412
  • Peer Reviewed / Open Access
• [Journal Article] Cardiac lymphatic dysfunction causes drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo. (2019)
  • Author(s): Amamizu H, Matsumoto Y, Morosawa S, Ohyama K, Uzuka H, Hirano M, Nishimiya K, Gokon Y, Watanabe-Asaka T, Hayashi M, Miyata S, Kamei T, Kawai Y, Shimokawa H.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 39 Pages: 741-753
  • Peer Reviewed / Open Access
• [Journal Article] Impacts of hippocampal blood flow on changes in left ventricular wall thickness in patients with chronic heart failure. (2019)
  • Author(s): Suzuki H, Matsumoto Y, Sugimura K, Takahashi J, Miyata S, Fukumoto Y, Taki Y, Shimokawa H.
  • Journal Title: International Journal of Cardiology. Volume: 299 Pages: 75-80
  • Peer Reviewed / Open Access
• [Journal Article] Coronary artery spasm and perivascular adipose tissue inflammation: Insights from translational imaging research. (2019)
  • Author(s): Ohyama K, Matsumoto M, Shimokawa H.
  • Journal Title: Eur Cardiol. Volume: 14 Pages: 6-9
  • Peer Reviewed / Open Access
• [Journal Article] Coronary Functional Abnormalities in Patients With Angina and Nonobstructive Coronary Artery Disease. (2019)
  • Author(s): Suda A, Takahashi J, Hao K, Kikuchi Y, Shindo T, Ikeda S, Sato K, Sugisawa J, Matsumoto Y, Miyata S, Sakata Y, Shimokawa H.
  • Journal Title: J Am Coll Cardiol. Volume: 74 Pages: 2350-2360
  • Peer Reviewed / Open Access
• [Journal Article] Disappearance of angiodysplasia following transcatheter aortic valve implantation in a patient with Heyde’s Syndrome: A case report and review of the literature. (2019)
  • Author(s): Tsuchiya S, Matsumoto M, Doman T, Fujiya T, Sugisawa J, Suda A, Sato K, Ikeda K, Shindo T, Kikuchi Y, Hao K, Takahashi J, Hatta W, Koike T, Masamune A, Saiki Y, Horiuchi H, Shimokawa H.
  • Journal Title: J Atheroscler Throm. Volume: 27 Pages: 271-277
  • NAID: 130007804192
  • Peer Reviewed / Open Access
• [Presentation] TAVI後の心臓リハビリテーション (2021)
  • Author(s): 松本泰治
  • Organizer: 日本心臓リハビリテーション学会総会
  • Invited
• [Presentation] 構造的心疾患インターベンションと周術期リハ (2021)
  • Author(s): 松本泰治
  • Organizer: 第84回日本循環器学会学術集会 トピックス：心臓リハビリテーション
  • Invited
• [Book] Coronary Vasomotion Abnormalities: Treatment of Coronary Artery Spasm (2020)
  • Author(s): Yasuharu Matsumoto, Hiroaki Shimokawa
  • Total Pages: 162
  • Publisher: Springer
  • ISBN: 9789811575938
• [Book] 冠動脈攣縮に対する腎交感神経除神経術. (2019)
  • Author(s): 松本泰治 下川宏明
  • Total Pages: 2
  • Publisher: 医学のあゆみ.医歯薬出版株式会社