大動脈弁狭窄症における大動脈弁石灰化に特異的な病態メカニズムのスクリーニング

2023 Fiscal Year Annual Research Report

• Project/Area Number: 21K16097
• Research Institution: Juntendo University
• Principal Investigator: 土井 信一郎 順天堂大学, 医学部, 助教 (10648158)
• Project Period (FY): 2021-04-01 – 2024-03-31
• 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 Annual Research Achievements

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(Transcatheter aortic valve implantation: TAVI)が施行された症例を対象とし、1) TAVI術前のCTから、大動脈弁と大動脈・冠動脈石灰化を定量化する。すなわち、大動脈弁石灰化容積(mm3)、横隔膜から3椎体分の下行大動脈壁の石灰化容積(Agatston score)、冠動脈の石灰化スコア(Agatston score)を体表面積で補正して算出する。2) TAVI施行前の血清から、これまでに知られている骨形成・炎症・動脈硬化・加齢因子を測定(リン、カルシウム、intact PTH, BMP, Osteopontin, Osteocalcin, sRANKL, Sortilin, S100A8/A9, 高感度CRP, TNFα, IL-6, IL-1β, Lp(a), テロメラーゼ活性など)し、さらに血清中のエクソソームを単離して、その中にあるmicro RNAやnon-coding RNAをそれぞれmiRNA, ncRNAアレイを用いてスクリーニングする。その上で、まずは1)と2)の相関を検討し、大動脈弁の石灰化と特異的に相関を認めるタンパク、あるいはエクソソームmicro RNA, noncoding RNAを同定、さらにその中で、予後すなわちTAVI後の死亡や心不全の発症と関連のある因子を同定する。

Research Products

• [Journal Article] Predictors for all-cause mortality in men after transcatheter aortic valve replacement: A report from the LAPLACE-TAVI registry (2023)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Discrepancy between invasive and echocardiographic transvalvular gradient after TAVI: Insights from the LAPLACE-TAVI registry (2023)
  • 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
  • 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 registry (2023)
  • 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 Pages: 45～54
  • DOI: 10.1007/s11239-023-02800-2
  • Peer Reviewed / Open Access
• [Presentation] A Case struggling with THV selection based on Annulus and Valsalva sinus sizes, complicated by coronary artery occlusion (2024)
  • 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
  • Int'l Joint Research
• [Presentation] Impact of SAPIEN3 Ultra RESILIA on improvement of valve performance: Insights from the LAPLACE-TAVI registry (2024)
  • 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
  • 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 registry (2024)
  • 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
  • Int'l Joint Research
• [Presentation] Impact of Osteoporotic risk Undergoing Transcatheter Aortic Valve Replacement; A Report from the LAPLACE-TAVI Registry (2024)
  • 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
  • Int'l Joint Research
• [Presentation] Outcomes of Transfemoral vs Alternative Approaches in Transcatheter Aortic Valve Implantation for Dialysis: an Analysis of the LAPLACE TAVI Registry (2024)
  • 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
  • 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 registry (2024)
  • 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
  • Int'l Joint Research
• [Presentation] Characteristics and Clinical Outcome of Normal-Flow Low-Gradient Aortic Stenosis Patients Undergoing TAVI -LAPLACE TAVI registry (2024)
  • 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
  • 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
  • Int'l Joint Research / Invited
• [Presentation] Complication Session (2023)
  • Author(s): 土井 信一郎
  • Organizer: Tokyo Percutaneous Cardiovascular Intervention Conference 2023
  • 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
  • Invited
• [Presentation] Impact of Type of Transcatheter Heart Valve and Anatomic Features on Complexity of Percutaneous Coronary Intervention in Patients After Transcatheter Aortic Valve Replacement (2023)
  • 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
  • Int'l Joint Research
• [Presentation] Prognostic Impact of Patient-Prosthesis Mismatch and Paravalvular Leak after TAVI (2023)
  • 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
  • Int'l Joint Research