The autoimmune mechanism for the onset and progression of heart failure with preserved ejection fraction

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: National Defense Medical College
• Principal Investigator: Nagatomo Yuji 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 内科学, 准教授 (70348647)
• Co-Investigator(Kenkyū-buntansha): 香坂 俊 慶應義塾大学, 医学部(信濃町), 講師 (30528659)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 抗心筋自己抗体 / 心不全

Outline of Final Research Achievements

A total of 377 patients who were hospitalizsed due to acute decompensated heart failure were registered. Blood samples were collected and autoantibodies against beta1-adrenergic receptors (beta1AR-AAb) belonging to IgG3 and the other subclasses were measured by ELISA method. Positivity of beta1AR-AAb was 16% in IgG3 and 20% in non-IgG3. Positivity was similar between heart failure with reduced ejection fraction and preserved ejection fraction. The patients who received beta-blockers before admission showed lower positivity and titer of IgG-beta-1AR-AAb. All cause mortality during hospitalization and after discharge was both higher in patients with IgG3- beta-1AR-AAb compared to the others. This trend was observed in the patients who did not receive beta-blockers but such difference was not observed in the patients who received beta-blockers. Analysis of microbiota showed the association of microbitoa with inflammatory markers.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

今回IgG3に属するβ1AR-AAb陽性患者は予後不良であり、β遮断薬の投与が同抗体陽性患者で有効である可能性が示唆された。またこの結果は左室駆出率に関わらず同様であった。左室駆出率の保たれた心不全（HFpEF）に対するβ遮断薬の臨床的有用性についてはこれまで結論が出ていない。本研究の結果からはIgG3-β1AR-AAb陽性患者ではβ遮断薬が有効である可能性がある。HFpEF患者において同抗体の測定が予後不良患者群、さらにβ遮断薬の有効な患者群の同定に有用である可能性がある。腸内細菌叢変化は炎症と関連しており、腸内細菌叢に対する治療介入の可能性について今後さらなる研究が必要である。