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Histological evaluation of atrial substrate in patients with atrial fibrillation

Research Project

Project/Area Number 21K08056
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionSaga University

Principal Investigator

YAMAGUCHI TAKANORI  佐賀大学, 医学部, 准教授 (70834810)

Co-Investigator(Kenkyū-buntansha) 野出 孝一  佐賀大学, 医学部, 教授 (80359950)
白木 綾  佐賀大学, 医学部, 特任教授 (50638252)
福井 暁  大分大学, 医学部, 助教 (70631381)
石井 悠海  大分大学, 医学部, 客員研究員 (20835607)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心房細動 / 線維化 / 心房生検 / 構造的リモデリング / 病理組織学 / 脳梗塞 / 組織学的評価 / カテーテルアブレーション / 病理
Outline of Research at the Start

高齢化に伴い心房細動患者が増加し、合併する脳塞栓症、心不全、突然死の予防が課題となっている。本研究は、心房細動アブレーション時に心房からの生検を行い、病理学的所見から心房細動の機序や進行度を評価し、またカテーテルアブレーション後の予後や再発に関連する因子を探索することを目的とした研究である。

Outline of Final Research Achievements

We have developed an intracardiac echocardiography-guided endomyocardial atrial biopsy technique that enables histopathological evaluation of atrial tissue. A total of 243 atrial biopsy specimens were analyzed.
We revealed that not only fibrosis, but also an increase in intercellular space that precedes fibrosis, myofibril loss, decreased myocardial nuclear density as a surrogate for myocardial cell number, and amyloid deposition were associated with atrial voltage reduction, which is a surrogate marker for atrial degeneration. Amyloid deposition in atrial tissue was observed in 4% of cases. In the future, multi-omics analysis will be conducted to elucidate the mechanism of atrial fibrillation, stratify patients, and predict prognosis.

Academic Significance and Societal Importance of the Research Achievements

心房細動は我が国おいて近い将来100万人に達すると予想され、脳梗塞や心不全を合併し、社会・経済的負担の大きな疾患である。心房細動に対する薬物療法および非薬物療法(カテーテルアブレーションなど)への治療反応性は個体差があり、個別化医療を目指すべき疾患である。壁の薄い心房からの生検は不可能とされてきたが、我々は心房生検を開発し、心房細動症例の心房筋の病理組織学的解析が可能となった。この心房生検による病理組織学的解析は、マルチオミックス解析とともに、心房細動の機序の解明治療反応性や予後予測など、個別化医療への足掛かりとなるであろう。

Report

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

    (21 results)

All 2024 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (18 results) (of which Invited: 2 results)

  • [Journal Article] Histological validation of atrial structural remodelling in patients with atrial fibrillation2023

    • Author(s)
      Yuya Takahashi, Takanori Yamaguchi, Toyokazu Otsubo, Kana Nakashima, Kodai Shinzato, Ryosuke Osako, Shigeki Shichida, Yuki Kawano, Akira Fukui, Atsushi Kawaguchi, Shinichi Aishima, Tsunenori Saito, Naohiko Takahashi, Koichi Node
    • Journal Title

      European Heart Journal

      Volume: 44 Issue: 35 Pages: 3339-3353

    • DOI

      10.1093/eurheartj/ehad396

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histological validation of atrial structural remodelling in patients with atrial fibrillation 心房細動患者における心房構造的リモデリングの組織学的検証2023

    • Author(s)
      山口尊則
    • Journal Title

      月刊心臓

      Volume: 55

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Atrial Structural Remodeling in Patients With Atrial Fibrillation Is a Diffuse Fibrotic Process: Evidence From High-Density Voltage Mapping and Atrial Biopsy.2022

    • Author(s)
      Yamaguchi T, Otsubo T, Takahashi Y, Nakashima K, Fukui A, Hirota K, Ishii Y, Shinzato K, Osako R, Tahara M, Kawano Y, Kawaguchi A, Aishima S, Takahashi N, Node K.
    • Journal Title

      Journal of the American Heart Assocication

      Volume: 11 Issue: 6

    • DOI

      10.1161/jaha.121.024521

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Approaching the Histopathology of Atrial Cardiomyopathy and Atrial Fibrillation: Evidence from Atrial Biopsy2024

    • Author(s)
      Takanori Yamaguchi
    • Organizer
      Japanese Circulation Society 2024
    • Related Report
      2023 Annual Research Report
  • [Presentation] AF Histology and Substrate2023

    • Author(s)
      Takanori Yamaguchi
    • Organizer
      Korean Heart Rhythm
    • Related Report
      2023 Annual Research Report
  • [Presentation] Evaluation of Atrial Substrate for AF2023

    • Author(s)
      Takanori Yamaguchi
    • Organizer
      Tokyo-Taipei-Seoul Arrhythmia Joint Conference
    • Related Report
      2023 Annual Research Report
  • [Presentation] 心房生検による心房細動の組織学的評価2023

    • Author(s)
      山口尊則
    • Organizer
      第269回日本循環器学会関東甲信越地方会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 心房細動の個別化医療を目指してー心房生検とゲノム・オミックス解析ー2023

    • Author(s)
      山口尊則
    • Organizer
      第18回九州遺伝子診断研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Histological Validation of Atrial Fibrillation Substrate2023

    • Author(s)
      Takanori Yamaguchi
    • Organizer
      Korean Heart Rhythm Society AF Summit
    • Related Report
      2023 Annual Research Report
  • [Presentation] 加齢に伴う心房細動発症のメカニズムー心房病理に基づく考察ー2023

    • Author(s)
      山口尊則
    • Organizer
      脳心血管抗加齢研究会第19回学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 心房細動における構造的リモデリングの組織学的検証2023

    • Author(s)
      山口尊則
    • Organizer
      第45回心筋生検研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Pathology of Atrial Fibrillation: Evidence from Atrial Biopsy2023

    • Author(s)
      山口尊則
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Histological Evidence of Atrial Cardiomyopathy in Patients with Atrial Fibrillation2022

    • Author(s)
      Takanori Yamaguchi
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Is Aging a Determinant of Atrial Fibrosis? -Evidence from Atrial Biopsy in Patients with Atrial Fibrillation2022

    • Author(s)
      Toyokazu Otsubo, Takanori Yamaguchi, Yuya Takahashi, Kana Nakashima, Kodai Shinzato, Ryosuke Osako, Shigeki Shichida, Yuki Kawano, Akira Fukui, Kei Hirota, Naohiko Takahashi, Koichi Node
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
  • [Presentation] Impact of Atrial Amyloid Deposition on Left Atrial Voltage in Patients with Atrial Fibrillation -Evidence from Atrial Biopsy-2022

    • Author(s)
      Kana Nakashima, Takanori Yamaguchi, Toyokazu Otsubo, Yuya Takahashi, Kodai Shinzato, Ryosuke Osako, Shigeki Shichida, Yuki Kawano, Akira Fukui, Kei Hirota, Naohiko Takahashi, Koichi Node
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
  • [Presentation] Strong Association between Left Atrial Strain and the Extent of Atrial Histological Fibrosis in Patients with Atrial Fibrillation2022

    • Author(s)
      Yuya Takahashi, Takanori Yamaguchi, Toyokazu Otsubo, Kana Nakashima, Kodai Shinzato, Ryosuke Osako, Shigeki Shichida, Yuki Kawano, Akira Fukui, Kei Hirota, Naohiko Takahashi, Koichi Node
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
  • [Presentation] Histological Determinants of Atrial Bipolar Voltage in Patients with Atrial Fibrillation2022

    • Author(s)
      Yuya Takahashi, Takanori Yamaguchi, Toyokazu Otsubo, Kana Nakashima, Kodai Shinzato, Ryosuke Osako, Shigeki Shichida, Yuuki Kawano, Akira Fukui, Kei Hirota, Naohiko Takahashi, Koichi Node
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
  • [Presentation] Relationship between Atrial Electrograms and Histological Fibrosis in Atrial Fibrillation -Evidence from Atrial Septum Biopsy2022

    • Author(s)
      Yuki Kawano, Takanori Yamaguchi, Toyokazu Otsubo, Yuya Takahashi, Kana Nakashima, Kodai Shinzato, Ryosuke Osako, Shigeki Shichida, Akira Fukui, Kei Hirota, Naohiko Takahashi, Koichi Node
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
  • [Presentation] What are the histological changes associated with aging in atrial myocardium in patients with atrial fibrillation? ーEvidence from Atrial Septal Biopsyー2022

    • Author(s)
      Kodai Shinzato, Takanori Yamaguchi, Toyokazu Otsubo, Yuya Takahashi, Kana Nakashima, Ryosuke Osako, Shigeki Shichida, Yuki Kawano, Akira Fukui, Kei Hirota, Naohiko Takahashi, Koichi Node
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
  • [Presentation] Relationships between histological fibrosis and persistency of atrial fibrillation -Evidence from Atrial Biopsy-2022

    • Author(s)
      Ryosuke Osako, Takanori Yamaguchi, Toyokazu Otsubo, Yuya Takahashi, Kana Nakashima, Kodai Shinzato, Shigeki Shichida, Yuki Kawano, Akira Fukui, Kei Hirota, Naohiko Takahashi, Koichi Node
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report
  • [Presentation] Relationship between histological changes of atrial mitochondria and atrial bipolar voltage in atrial fibrillation patients -sub-analysis of HEAL-AF2022

    • Author(s)
      Kei Hirota, Akira Fukui, Takanori Yamaguchi, Masaki Takahashi, Yumi Ishii, Toyokazu Otsubo, Yuya Takahashi, Kana Nakashima, Koichi Node, Naohiko Takahashi
    • Organizer
      The 86th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2021 Research-status Report

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

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