Emerging diagnostic methods and risk stratification for cardiac sarcoidosis

• Project/Area Number: 15K19402
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Hokkaido University (2017); National Cardiovascular Center Research Institute (2015-2016)
• Principal Investigator: Nagai Toshiyuki 北海道大学, 大学病院, 助教 (00528218)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 心臓サルコイドーシス / 免疫応答 / マクロファージ / 樹状細胞 / 病理組織診断

Outline of Final Research Achievements

The numbers of dendritic cells (DC) and macrophages were investigated in 95 consecutive cardiac sarcoidosis (CS) patients and 50 patients with nonischemic cardiomyopathy as controls. In CS patients with and without myocardial granulomas, CD209+ DC and CD68+ macrophages were more frequently observed (P<0.01) and CD163+M2 macrophages were less frequently observed (P<0.01) in nongranuloma sections compared to controls. Furthermore, the combination of decreased CD163+M2/CD68+ macrophage ratio and increased number of CD209+ DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7-100%) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas. In conclusions, increased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS.

Research Products

• [Journal Article] Myocardial Immunocompetent Cells and Macrophage Phenotypes as Histopathological Surrogates for Diagnosis of Cardiac Sarcoidosis in Japanese. (2016)
  • Author(s): Honda Y, Nagai T, Ikeda Y, Sakakibara M, Asakawa N, Nagano N, Nakai M, Nishimura K, Sugano Y, Ohta-Ogo K, Asaumi Y, Aiba T, Kanzaki H, Kusano K, Noguchi T, Yasuda S, Tsutsui H, Ishibashi-Ueda H, Anzai T.
  • Journal Title: Journal of the American Heart Association Volume: 5 Issue: 11
  • DOI: 10.1161/jaha.116.004019
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Discontinuation of Prednisolone Therapy on Risk of Cardiac Mortality Associated with Worsening Left Ventricular Dysfunction in Cardiac Sarcoidosis. (2016)
  • Author(s): Nagai T, Nagano N, Sugano Y, Asaumi Y, Aiba T, Kanzaki H, Kusano K, Noguchi T, Yasuda S, Ogawa H, Anzai T.
  • Journal Title: American Journal of Cardiology Volume: 117 Issue: 6 Pages: 966-71
  • DOI: 10.1016/j.amjcard.2015.12.033
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Usefulness of Dendritic Cells and Macrophage Phenotypes Infiltrated Into Myocardium for Diagnosis of Cardiac Sarcoidosis (2016)
  • Author(s): Nagai T, Honda Y, Ikeda Y, Sakakibara M, Asakawa N, Nagano N, Yasuda S, Tsutsui H, Ueda HI, Anzai T
  • Organizer: 第20回日本心不全学会学術集会
  • Place of Presentation: Sapporo
  • Year and Date: 2016-10-06
• [Presentation] 心臓サルコイドーシスにおけるステロイド療法の現状と今後の課題. (2016)
  • Author(s): 永井利幸，永野伸卓，菅野康夫，浅海泰栄，草野研吾，野口暉夫，安田聡，安斉俊久
  • Organizer: 第64回日本心臓病学会学術集会
  • Place of Presentation: Tokyo
  • Year and Date: 2016-09-23
  • Invited
• [Presentation] Corticosteriod Therapy for Cardiac Sarcoidosis (2016)
  • Author(s): Nagai T, Nagano N, Kusano K, Yasuda S, Anzai T.
  • Organizer: 第63回日本不整脈心電学会学術集会
  • Place of Presentation: Sapporo
  • Year and Date: 2016-07-14
  • Invited
• [Presentation] 心臓サルコイドーシスにおけるステロイド治療～開始と中止の至適タイミングをどのように考えるべきか～ (2016)
  • Author(s): 永井利幸，永野伸卓，菅野康夫，浅海泰栄，草野研吾，野口暉夫，安田聡，安斉俊久.
  • Organizer: 第2回日本心筋症研究会
  • Place of Presentation: Matsumoto
  • Invited
• [Presentation] 心臓サルコイドーシスにおけるステロイド治療の途中中止は左室機能障害の進行と関連して心臓死を増加させる． (2015)
  • Author(s): 永井利幸，永野伸卓, 菅野康夫, 相庭武司, 神崎秀明, 草野研吾, 野口輝夫, 安田聡, 小 川久雄, 安斉俊久．
  • Organizer: 第35回日本サルコイドーシス/肉芽腫性疾患学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2015-11-07
• [Presentation] Discontinuation of Corticosteroid Therapy Increases the Risk of Cardiac Mortality Associated with Progression of Left Ventricular Dysfunction in Cardiac Sarcoidosis. (2015)
  • Author(s): Nagai T, Nagano N, Sugano Y, Asaumi Y, Aiba T, Kanzaki H, Kusano K, Noguchi T, Yasuda S, Ogawa H, Anzai T.
  • Organizer: 第１９回日本心不全学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-10-22