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Clinical applications of plasma cell-free DNA as a predictor of prognosis after acute heart failure and myocardial infarction

Research Project

Project/Area Number 20K08436
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KAWAI Yasuyuki  金沢医科大学, 医学部, 教授 (40324157)

Co-Investigator(Kenkyū-buntansha) 藤林 幸輔  金沢医科大学, 医学部, 講師 (10633323)
藤原 純子  島根大学, 学術研究院医学・看護学系, 助教 (20346381)
若狭 稔  金沢医科大学, 医学部, 講師 (50468980)
竹下 治男  島根大学, 学術研究院医学・看護学系, 教授 (90292599)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordscell-free DNA / acute heart failure / apoptosis / 血漿遊離DNA / 急性心不全 / アポトーシス / 左室リモデリング / 心房細動 / 左房リモデリング / 急性心筋梗塞
Outline of Research at the Start

血漿遊離DNAが簡便かつ有用な左室リモデリングのバイオマーカーであるか否かを検証するため、以下の3つを検討する。①血漿遊離DNAが新規心不全患者で検出されるか否か、また②血漿遊離DNAの一部が心臓に由来しているか否か、③血漿遊離DNAが急性心不全及び急性心筋梗塞後の左室リモデリング評価による予後予測因子になり得るかどうかを明らかにすることである。

Outline of Final Research Achievements

The source of cell-free DNA (cfDNA) in patients with acute heart failure (AHF) is unknown. Therefore, we evaluated the transmayocardial arteriovenous differences of plasma cfDNA concentrations in patients with AHF.We enrolled 30 patients with AHF. Blood samples were obtained simultaneously at aortic root (AO) and at coronary sinus (CS). We evaluated the plasma levels of transmyocardial gradient of cfDNA concentration (delta cfDNA). Myocardial samples were subjected to histological examination.The mean levels of delta cfDNA in 18 patients were 3.1±3.5 microg/ml (positive group), in the other 12 patients were -3.1±2.4 microg/ml (negative group). In the histological evaluation, 7 of 18 patients (39%) in the positive group showed cardiac fibrosis, 9 of 12 patients (75%) in the negative group showed cardiac fibrosis.
We postulated myocardial apoptosis is occurring in the positive group without cardiac fibrosis and gradually would cause cardiac fibrosis.

Academic Significance and Societal Importance of the Research Achievements

急性心不全患者において冠静脈洞と大動脈基部のcfDNA濃度差の検討から、cfDNAが心臓で産生されたものかどうか、またその臨床的な意義は明らかにはならなかった。さらにcfDNAが負の値になる合理的な理由も説明ができなかった。したがってcfDNAが心疾患でどのような意義を持っているのかを今後さらに明らかにし、そのための研究方法を見出す必要がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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