Left Ventricular Contractile Force in Response to Heart Rate Variation, and Its Relation to Left Ventricular Reverse Remodeling

• Project/Area Number: 17K09490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Niigata University
• Principal Investigator: Kashimura Takeshi 新潟大学, 医歯学総合研究科, 特任准教授 (70419290)
• Co-Investigator(Kenkyū-buntansha): 南野 徹 新潟大学, 医歯学系, 教授 (90328063)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 心不全 / 左室収縮不全 / HFrEF / 頻脈 / 交互脈 / カルシウム / 心エコー / 非侵襲的 / リバースリモデリング / 心拍数 / 左室収縮力 / 循環器・高血圧

Outline of Final Research Achievements

Heart failure occurs when left ventricle (LV) pumps out only insufficient amount of blood. This is typically caused with LV systolic dysfunction characterized by a combination of dilated LV cavity and reduced LV contraction, which is, LV “remodeling”. On the other hand, LV reverse remodeling” means volume reduction of dilated LV cavity and restoration of LV contractile function after treatments.
Our research of LV systolic dysfunction focused on LV performance under heart rate variation. We found that in some patients LV could exert sufficient contraction evenly during tachycardia, but some could not and caused pulsus alternans, in which strong beat and weak beat appeared alternatingly despite regular pulse interval. Additionally, we found decrease in mitochondrial size suggesting impaired mitochondrial fusion in patients without reverse remodeling.

Academic Significance and Societal Importance of the Research Achievements

人口の高齢化にともない心不全患者さんが増加していることに注目が集まる一方、若年の重症心不全患者さんもいまだに多く、心臓移植やその待機期間を補助人工心臓で過ごす患者さんは年々増加している。若年者心不全の主体は「リモデリング」をともなう左室収縮不全であり、「リバースリモデリング」と関連する因子を見出しつつある意義は大きい。
心拍数の変化への応答不全（一拍おきにしか十分な収縮がえられない交互脈など）は心筋細胞が担っており、「リバースリモデリング」が生じない例で、ミトコンドリアの融合不全を示すことができたのは、心室筋機能を改善させるような今後の治療の糸口となる可能性があり、意義が大きい。

Research Products

• [Journal Article] Cardiac mitofusin-1 is reduced in non-responding patients with idiopathic dilated cardiomyopathy (2021)
  • Author(s): Hsiao YT, Shimizu I, Wakasugi T, Yoshida Y, Ikegami R, Hayashi Y, Suda M, Katsuumi G, Nakao M, Ozawa T, Izumi D, Kashimura T, Ozaki K, Soga T, Minamino T.
  • Journal Title: Sci Rep . Volume: 11 Issue: 1 Pages: 6722-6722
  • DOI: 10.1038/s41598-021-86209-y
  • Peer Reviewed / Open Access