Noble method for evaluation of the drug induced QT prolongation in patients with atrial fibrillation and associated gene abnormality

• Project/Area Number: 24591040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: University of Toyama
• Principal Investigator: Mizumaki Koichi 富山大学, 臨床研究・倫理センター, 特命准教授 (90313618)
• Co-Investigator(Kenkyū-buntansha): ICHIDA FUKIKO 富山大学, 大学院医学薬学研究部(医学), 准教授 (30223100)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: QT延長症候群 / 心房細動 / ホルター心電図 / 遺伝子解析 / イオンチャネル / 薬剤性QT延長症候群 / 遺伝子

Outline of Final Research Achievements

We established reliable methods for assessing QT/RR relation during atrial fibrillation (AF) using Holter ECG. Moreover, in patients with paroxysmal AF, bradycardia-dependent QT prolongation was attenuated during AF, and was corrected and gradually augmented along with continuation of SR, especially in patients receiving antiarrhythmic drugs. This could increase the risk of developing torsade de pointes (TdP). In both in vivo and in vitro studies, patients with KCNE1(G38S) had a rate-dependent repolarization abnormality similar to patients with LQT2, and therefore may have a potential risk to developTdP.

Research Products

• [Journal Article] Abnormal repolarization dynamics in a patient with KCNE1(G38S) who presented with torsades de pointes. (2016)
  • Author(s): Yamaguchi Y, Mizumaki K, Hata Y, Inoue H.
  • Journal Title: J Electrocardiol Volume: 49 Issue: 1 Pages: 94-98
  • DOI: 10.1016/j.jelectrocard.2015.10.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Time-Dependent Changes in QT Dynamics after Initiation and Termination of Paroxysmal Atrial Fibrillation (2015)
  • Author(s): Yamaguchi Y, Mizumaki K, Nishida K, Sakamoto T, Kataoka N, Nakatani Y, Inoue H.
  • Journal Title: Pacing Clin Electrophysiol Volume: 38 Issue: 12 Pages: 1418-1424
  • DOI: 10.1111/pace.12746
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A590T mutation in KCNQ1 C-terminal helix D decreases IKs channel trafficking and function but not Yotiao interaction. (2014)
  • Author(s): Kinoshita K, Komatsu T, Nishide K, Hata Y, Hisajima N, Takahashi H, Kimoto K, Aonuma K, Tushima E, Tabata T, Yoshida T, Mori H, Nishida K, Yamaguchi Y, Ichida F, Fukurotani K, Inoue H, Nishida N.
  • Journal Title: J Mol Cell Cardiol Volume: 72 Pages: 273-280
  • DOI: 10.1016/j.yjmcc.2014.03.019
  • Peer Reviewed / Open Access
• [Journal Article] Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit’s Modulatory Actions on Rapid and Slow Delayed Rectifier K⁺ Currents (2014)
  • Author(s): Yoshiaki Yamaguchi, Kohki Nishide, Mario Kato, Yukiko Hata, Koichi Mizumaki, Koshi Kinoshita, Yuki Nonobe, Toshihide Tabata, Tamotsu Sakamoto, Naoya Kataoka, Yosuke Nakatani, Fukiko Ichida, Hisashi Mori, Kenkichi Fukurotani, Hiroshi Inoue, MD, Naoki Nishida
  • Journal Title: Circulation Journal Volume: 78 Issue: 3 Pages: 610-618
  • DOI: 10.1253/circj.CJ-13-1126
  • NAID: 130003391006
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Characterization of a novel mutant KCNQ1 channel subunit lacking a large part of the C-terminal domain (2013)
  • Author(s): Katsuya Kimoto, Koshi Kinoshita, Tomoki Yokoyama, Yukiko Hata, Takuto Komatsu, Eikichi Tsushima, Kohki Nishide, Yoshiaki Yamaguchi, Koichi Mizumaki, Toshihide Tabata, Hiroshi Inoue, Naoki Nishida, Kenkichi Fukurotani
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 440 Issue: 2 Pages: 283-288
  • DOI: 10.1016/j.bbrc.2013.09.075
  • Peer Reviewed
• [Presentation] Postprandial augmentation of J-wave elevation in patients with idiopathic ventricular fibrillation (2016)
  • Author(s): Koichi Mizumaki, Naoya Kataoka, Yoshiaki Yamaguchi, Yosuke Nakatani, Tamotsu Sakamoto, Yasushi Tsujino, Kunihiro Nishida
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18
• [Presentation] Regional heterogeneity in bradycardia-dependent augmentation of J-wave elevation in patients with idiopathic ｖentricular ｆibrillation (2015)
  • Author(s): Koichi Mizumaki, Kunihiro Nishida, Yoshiaki Yamaguchi,, Yosuke Nakatani, Naoya Katnaoka, Tamotsu Sakamoto, Hiroshi Inoue
  • Organizer: The 8ｔｈＡｓｉａ Ｐａｃｉｆｉｃ Ｈｅａｒｔ Ｒｈｙｔｈｍ Ｓｏｃｉｅｔｙ
  • Place of Presentation: Melbourne
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] Role of autonomic nervous activity in patients with idiopathic ventricular fibrillation and long QT Syndrome. (2015)
  • Author(s): 水牧功一
  • Organizer: 第30回日本不整脈学会学術大会／第32回日本心電学会学術集会合同学術大会
  • Place of Presentation: 京都
  • Year and Date: 2015-07-28
  • Invited
• [Presentation] Abnormal repolarization dynamics in a patient with KCNE1(G38S) who demonstrated torsade de pointes. (2014)
  • Author(s): 4)Yamaguchi Y, Mizumaki K, Nishida K, Sakamoto T, Nakatani Y, Kataoka N, Inoue H.
  • Organizer: The 7th Asia Pacific Heart Rhythm Society
  • Place of Presentation: New Delhi
  • Year and Date: 2014-10-29 – 2014-11-01
• [Presentation] Abnormal repolarization dynamics during daily life in patients with D85N single nucleotide polymorphism of KCNE1 gene. (2013)
  • Author(s): Yamaguchi Y, Mizumaki K, Nishida K, Sakamoto T, Kataoka N, Hata Y, Kinoshita K, Ichida F, Nishida N, Inoue H.
  • Organizer: The 34th Annual Scientific Session of the Heart Rhythm Society
  • Place of Presentation: デンバー、アメリカ合衆国
• [Presentation] Abnormal repolarization dynamics during daily life in patients with G38S single nucleotide polymorphism of KCNE1 gene. (2012)
  • Author(s): Yamaguchi Y. , Mizumaki K., Nishida K., Iwamoto J., Nakatani Y., Kataoka N., Hata Y., Ichida F., Nishida N., Inoue H.
  • Organizer: Heart Rhythm Society`s 33rd Annual Scientific Sessions
  • Place of Presentation: ボストン, アメリカ合衆国
• [Presentation] 先天性QT延長症候群におけるQT/RR、T-wave peak-to-end(Tp-e)/RR関係の日内変動 (2012)
  • Author(s): 山口由明，水牧功一，西田邦洋，坂本 有，片岡直也，井上 博
  • Organizer: 第60回日本心臓病学会
  • Place of Presentation: 金沢
• [Presentation] D85N SNPを有するQT延長症候群例におけるホルター心電図でのQT/RR、T-wave peak-to-end/RR関係の解析． (2012)
  • Author(s): 山口由明，水牧功一，西田邦洋，坂本 有，片岡直也，井上 博
  • Organizer: 第29回日本心電学会
  • Place of Presentation: 幕張