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Screening for pathological mechanisms specific to aortic valve calcification in aortic stenosis.

Research Project

Project/Area Number 21K16097
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionJuntendo University

Principal Investigator

Doi Shinichiro  順天堂大学, 医学部, 助教 (10648158)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords大動脈弁狭窄症 / 経カテーテル的大動脈弁植え込み術 / 大動脈弁石灰化 / 動脈硬化
Outline of Research at the Start

本研究では、大動脈弁狭窄症(Aortic Stenosis: AS)の進行に対する予防・治療アプローチを開発することを目標とし、ASの進行メカニズムを動脈硬化と比較しながら検討する。具体的には、ASが進行して経カテーテル的大動脈弁植え込み術が施行された症例の血清から骨代謝・炎症・動脈硬化・加齢関連のバイオマーカーと、エクソソーム micro RNAとnon-coding RNA をスクリーニングし、胸部CT画像から大動脈弁・下行大動脈・冠動脈の石灰化を定量化したものとの相関を検討することで、大動脈弁石灰化に特異的に関連するバイオマーカーを特定しうる。

Outline of Final Research Achievements

The aim of this study was to develop preventive and therapeutic approaches for the progression of aortic stenosis (AS), and the study included patients with advanced AS who underwent transcatheter aortic valve implantation (TAVI). From both epidemiological and translational studies, we identified prognostic factors after TAVI and investigated the mechanisms of AS progression compared with those of atherosclerosis, in order to investigate their utility and to develop preventive and therapeutic approaches for the progression of AS.

Academic Significance and Societal Importance of the Research Achievements

多施設共同TAVIレジストリデータベースを用いた臨床・疫学的な視点からの解析では、数年以上の中長期的な予後に影響を及ぼす因子を検討し、TAVI後に肺高血圧が残存することが予後不良因子となることを示した。この知見は肺高血圧が不可逆になる前に弁置換を行う必要があることを示唆している。
TAVIを施行された症例の血清のHDL機能(組織からコレステロールを回収する能力: コレステロール引き抜き能)を測定すると、男性でのみHDLによるコレステロール引き抜き能が高いほど、大動脈弁石灰化が少ないことが明らかとなった。今後、HDLのコレステロール引き抜き能を規定する因子の数値化も含めさらなる検討が必要である。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (28 results)

All 2024 2023 2022

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (22 results) (of which Int'l Joint Research: 21 results,  Invited: 3 results)

  • [Journal Article] Predictors for all-cause mortality in men after transcatheter aortic valve replacement: A report from the LAPLACE-TAVI registry2023

    • Author(s)
      Nishida Kota、Saji Mike、Higuchi Ryosuke、Takamisawa Itaru、Nanasato Mamoru、Tamura Harutoshi、Sato Kei、Yokoyama Hiroaki、Doi Shinichiro、Okazaki Shinya、Onishi Takayuki、Tobaru Tetsuya、Takanashi Shuichiro、Ozaki Kazuyuki、Inomata Takayuki、Isobe Mitsuaki
    • Journal Title

      IJC Heart & Vasculature

      Volume: 48 Pages: 101257-101257

    • DOI

      10.1016/j.ijcha.2023.101257

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrepancy between invasive and echocardiographic transvalvular gradient after TAVI: Insights from the LAPLACE-TAVI registry2023

    • Author(s)
      Yamazaki Chiemi、Higuchi Ryosuke、Saji Mike、Takamisawa Itaru、Nanasato Mamoru、Doi Shinichiro、Okazaki Shinya、Tamura Harutoshi、Sato Kei、Yokoyama Hiroaki、Onishi Takayuki、Tobaru Tetsuya、Shimizu Atsushi、Takanashi Shuichiro、Isobe Mitsuaki
    • Journal Title

      International Journal of Cardiology

      Volume: 386 Pages: 17-23

    • DOI

      10.1016/j.ijcard.2023.05.010

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of periprocedural bleeding on mid-term outcome in nonagenarians who underwent transcatheter aortic valve implantation: insights from LAPLACE registry2023

    • Author(s)
      Fukutomi Motoki、Onishi Takayuki、Ando Tomo、Higuchi Ryosuke、Hagiya Kenichi、Saji Mike、Takamisawa Itaru、Iguchi Nobuo、Takayama Morimasa、Shimizu Atsushi、Shimizu Jun、Doi Shinichiro、Okazaki Shinya、Sato Kei、Tamura Harutoshi、Yokoyama Hiroaki、Takanashi Shuichiro、Tobaru Tetsuya
    • Journal Title

      Journal of Thrombosis and Thrombolysis

      Volume: 56 Issue: 1 Pages: 45-54

    • DOI

      10.1007/s11239-023-02800-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Favorable Prognosis in Patients with Recovered Pulmonary Hypertension after TAVI: An Analysis of the LAPLACE-TAVI Registry2023

    • Author(s)
      Koike Takuma、Iwata Hiroshi、Chikata Yuichi、Doi Shinichiro、Naito Ryo、Yasuda Hidetoshi、Funamizu Takehiro、Endo Hirohisa、Miyazaki Sakiko、Okazaki Shinya、Higuchi Ryosuke、Takamisawa Itaru、Sato Kei、Tamura Harutoshi、Yokoyama Hiroaki、Tobaru Tetsuya、Takanashi Shuichiro、Tabata Minoru、Minamino Tohru
    • Journal Title

      Journal of Clinical Medicine

      Volume: 12 Issue: 2 Pages: 729-729

    • DOI

      10.3390/jcm12020729

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Midterm Outcomes of Underweight Patients Undergoing Transcatheter Aortic Valve Implantation2023

    • Author(s)
      Tezuka Taiyo、Higuchi Ryosuke、Hagiya Kenichi、Saji Mike、Takamisawa Itaru、Nanasato Mamoru、Iguchi Nobuo、Shimizu Atsushi、Shimizu Jun、Doi Shinichiro、Okazaki Shinya、Sato Kei、Tamura Harutoshi、Yokoyama Hiroaki、Onishi Takayuki、Tobaru Tetsuya、Takanashi Shuichiro、Takayama Morimasa
    • Journal Title

      JACC: Asia

      Volume: 3 Issue: 1 Pages: 78-89

    • DOI

      10.1016/j.jacasi.2022.08.014

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognosis of patients with active cancer undergoing transcatheter aortic valve implantation: An insight from Japanese multicenter registry2022

    • Author(s)
      Kojima Yoshimasa、Higuchi Ryosuke、Hagiya Kenichi、Saji Mike、Takamisawa Itaru、Iguchi Nobuo、Takanashi Shuichiro、Doi Shinichiro、Okazaki Shinya、Sato Kei、Tamura Harutoshi、Takayama Morimasa、Ikeda Takanori、Isobe Mitsuaki
    • Journal Title

      IJC Heart & Vasculature

      Volume: 40 Pages: 101045-101045

    • DOI

      10.1016/j.ijcha.2022.101045

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A Case struggling with THV selection based on Annulus and Valsalva sinus sizes, complicated by coronary artery occlusion2024

    • Author(s)
      Ryota Nishio, Shinichiro Doi, Norihito Takahashi, Tomotaka Dohi, Sakiko Miyazaki, Seiji Koga, Hiroshi Iwata, Shinichiro Fujimoto, Shinya Okazaki, Minoru Tabata, Tohru Minamino
    • Organizer
      PCR Tokyo Valves 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of SAPIEN3 Ultra RESILIA on improvement of valve performance: Insights from the LAPLACE-TAVI registry2024

    • Author(s)
      Norihito Takahashi, Shinichiro Doi, Tomotaka Dohi, Takuma Koike, Soshi Moriya, Ryota Nishio, Hiroshi Iwata, Shinya Okazaki, Ryosuke Higuchi, Itaru Takamisawa, Mike Saji, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Tetsuya Tobaru, Shuichiro Takanashi, Minoru Tabata, Tohru Minamino
    • Organizer
      第88回日本循環器学会学術集会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prognostic Impact of Prosthesis-patient Mismatch and Paravalvular Leakage after Transcatheter Aortic Valve Implantation: an Insight from the LAPLACE-TAVI registry2024

    • Author(s)
      Kazuya Sakamoto, Ryosuke Higuchi, Kenichi Hagiya, Mitsunobu Kitamura, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Atsushi Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Takayuki Ohnishi, Tetsuya Tobaru, Shuichiro Takanashi, Mitsuaki Isobe
    • Organizer
      第88回日本循環器学会学術集会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of Osteoporotic risk Undergoing Transcatheter Aortic Valve Replacement; A Report from the LAPLACE-TAVI Registry2024

    • Author(s)
      Takashi Funaki, Ryosuke Higuchi, Kenichi Hagiya, Mitsunobu Kitamura, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Atsushi Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Takayuki Ohnishi, Tetsuya Tobaru, Shuichiro Takanashi, Mitsuaki Isobe
    • Organizer
      第88回日本循環器学会学術集会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Outcomes of Transfemoral vs Alternative Approaches in Transcatheter Aortic Valve Implantation for Dialysis: an Analysis of the LAPLACE TAVI Registry2024

    • Author(s)
      Takayuki Onishi, Motoki Fukutomi, Ryosuke Higuchi, Kenichi Hagiya, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Jun Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Atsushi Shimizu, Shuichiro Takanashi, Tetsuya Tobaru
    • Organizer
      第88回日本循環器学会学術集会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of tricuspid valve regurgitation severity for predicting after TAVI for dialysis patients with severe aortic stenosis: The LAPLACE-TAVI registry2024

    • Author(s)
      Shunsuke Edamura, Harutoshi Tamura, Ryosuke Higuchi, Kenichi Hagiya, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Jun Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Hiroaki Yokoyama, Atsushi Shimizu, Shuichiro Takanashi, Tetsuya Tobaru, Masafumi Watanabe
    • Organizer
      第88回日本循環器学会学術集会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characteristics and Clinical Outcome of Normal-Flow Low-Gradient Aortic Stenosis Patients Undergoing TAVI -LAPLACE TAVI registry2024

    • Author(s)
      Maiko Senoo, Hiroaki Yokoyama, Ryosuke Higuchi, Kenichi Hagiya, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Jun Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Atsushi Shimizu, Shuichiro Takanashi, Tetsuya Tobaru, Hirofumi Tomita
    • Organizer
      第88回日本循環器学会学術集会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ニューノーマルの植込み術2023

    • Author(s)
      土井 信一郎
    • Organizer
      Tokyo Percutaneous Cardiovascular Intervention Conference 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Complication Session2023

    • Author(s)
      土井 信一郎
    • Organizer
      Tokyo Percutaneous Cardiovascular Intervention Conference 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pre BAV再考  TAVI手技におけるBAVを再考する2023

    • Author(s)
      土井 信一郎
    • Organizer
      ストラクチャークラブ・ジャパン ライブデモンストレーション2023
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Impact of Type of Transcatheter Heart Valve and Anatomic Features on Complexity of Percutaneous Coronary Intervention in Patients After Transcatheter Aortic Valve Replacement2023

    • Author(s)
      Norihito Takahashi, Shinichiro Doi, Tomotaka Dohi, Endo Hirohisa, Hiroki Nishiyama, Iwao Okai, Sakiko Miyazaki, Hiroshi Iwata, Shinichiro Fujimoto, Shinya Okazaki, Tabata Minoru, Tohru Minamino
    • Organizer
      American Heart Association Scientific Sessions 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prognostic Impact of Patient-Prosthesis Mismatch and Paravalvular Leak after TAVI2023

    • Author(s)
      Kazuya Sakamoto, Ryosuke Higuchi, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Shinichiro Doi, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Tetsuya Tobaru
    • Organizer
      PCR London Valves 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cardiovascular outcome based on the cardiac damage staging in patients undergoing transcatheter aortic valve implantation: the LAPLACE-TAVI registry data analysis2023

    • Author(s)
      石橋 典幸, 樋口 亮介, 萩谷 健一, 北村 光信, 佐地 真育, 髙見澤 格, 七里 守, 井口 信雄, 高山 守正, 清水 篤, 土井 信一郎, 岡崎 真也, 佐藤 圭, 田村 晴俊, 横山 公章, 大西 隆行, 桃原 哲也, 高梨 秀一郎, 磯部 光章
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mid-term outcome after transcatheter aortic valve replacement in patients with dementia: an insight from the LAPLACE-TAVI registry2023

    • Author(s)
      Takashi Funaki, Ryosuke Higuchi, Kenichi Hagiya, Mitsunobu Kitamura, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Atsushi Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Takayuki Ohnishi, Tetsuya Tobaru, Shuichiro Takanashi, Mitsuaki Isobe
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 5- to 10-Year Outcome after Transcatheter Aortic Valve Implantation: an Analysis from the LAPLACE-TAVI Registry2023

    • Author(s)
      坂本 和哉, 樋口 亮介, 萩谷 健一, 北村 光信, 佐地 真育, 髙見澤 格, 七里 守, 井口 信雄, 高山 守正, 土井 信一郎, 岡崎 真也, 佐藤 圭, 田村 晴俊, 横山 公章, 桃原 哲也, 大西 隆行, 清水 篤, 高梨 秀一郎, 磯部 光章
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prognostic impact of echographic parameters regarding diastolic dysfunction in patients with preserved ejection fraction following TAVI: Insights from LAPLACE-TAVI registry2023

    • Author(s)
      Soshi Moriya, Hiroshi Iwata, Yuichi Chikata, Shinichiro Doi, Shinya Okazaki, Ryosuke Higuchi, Kenichi Hagiya, Mike Saji, Itaru Takamisawa, Nobuo Iguchi, Morimasa Takayama, Atsushi Shimizu, Harutoshi Tamura, Hiroaki Yokoyama, Kei Sato, Takayuki Ohnishi, Shuichiro Takanashi, Tetsuya Tobaru, Tohru Minamino
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] No Antiplatelet Versus Single Antiplatelet Therapy after Transcatheter Aortic Valve Implantation: An Insight from the LAPLACE-TAVI Registry2023

    • Author(s)
      Takayuki Onishi, Motoki Fukutomi, Ryosuke Higuchi, Kenichi Hagiya, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Jun Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Atsushi Shimizu, Shuichiro Takanashi, Tetsuya Tobaru
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impact of prior heart failure hospitalization on clinical outcomes of patients after transcatheter aortic valve implantation: Insights from LAPLACE registry2023

    • Author(s)
      Motoki Fukutomi, Takayuki Ohnishi, Tomo Ando, Ryosuke Higuchi, Kenichi Hagiya, Mike Saji, Itaru Takamisawa, Nobuo Iguchi, Morimasa Takayama, Atsushi Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Shuichiro Takanashi, Tetsuya Tobaru
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pacemaker Implantation after Transcatheter Aortic Valve Implantation for Structure Valve Deterioration: An Assessment from the LAPLACE TAVI Registry2023

    • Author(s)
      佐藤 圭, 石山 将希, 杉浦 英美喜, 大森 拓, 栗田 泰郎, 樋口 亮介, 萩谷 健一, 佐地 真育, 髙見澤 格, 七里 守, 井口 信雄, 高山 守正, 清水 篤, 清水 淳, 土井 信一郎, 岡崎 真也, 田村 晴俊, 横山 公章, 大西 隆行, 桃原 哲也, 土肥 薫
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preoperative LAVI and LVMI predicts prognosis in paradoxical low-flow low-gradient aortic stenosis after transcatheter aortic valve implantation: The LAPLACE-TAVI registry2023

    • Author(s)
      枝村 峻佑, 田村 晴俊, 永井 貴之, 髙畑 葵, 和根崎 真大, 西山 悟史, 樋口 亮介, 萩谷 健一, 佐地 真育, 髙見澤 格, 七里 守, 井口 信雄, 高山 守正, 清水 篤, 清水 淳, 土井 信一郎, 岡崎 真也, 佐藤 圭, 横山 公章, 大西 隆行, 桃原 哲也, 高梨 秀一郎, 渡辺 昌文
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Long-term outcomes with balloon-expandable and self-expandable prosthesis in patients undergoing transcatheter aortic valve implantation for very severe aortic stenosis-LAPLACE-TAVI registry2023

    • Author(s)
      横山 公章, 齊藤 良明, 村田 賢祐, 對馬 迪子, 妹尾 麻衣子, 市川 博章, 西崎 史恵, 澁谷 修司, 花田 賢二, 樋口 亮介, 萩谷 健一, 佐地 真育, 髙見澤 格, 七里 守, 井口 信雄, 高山 守正, 清水 篤, 高梨 秀一郎, 清水 淳, 田村 晴俊, 土井 信一郎, 岡崎 真也, 佐藤 圭, 大西 隆行, 桃原 哲也, 富田 泰史
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Outcome after Transcatheter Aortic Valve Implantation in Dialysis Patients: An Assessment from the LAPLACE-TAVI Registry2023

    • Author(s)
      Takayuki Onishi, Motoki Fukutomi, Ryosuke Higuchi, Kenichi Hagiya, Mike Saji, Itaru Takamisawa, Mamoru Nanasato, Nobuo Iguchi, Morimasa Takayama, Jun Shimizu, Shinichiro Doi, Shinya Okazaki, Kei Sato, Harutoshi Tamura, Hiroaki Yokoyama, Atsushi Shimizu, Shuichiro Takanashi, Tetsuya Tobaru
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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