Construction of A tool for prediction of sudden cardiac death using digital ECG data

• Project/Area Number: 18K08075
• 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: Okayama University
• Principal Investigator: MORITA Hiroshi 岡山大学, 医歯薬学総合研究科, 教授 (50322227)
• Co-Investigator(Kenkyū-buntansha): 渡邊 敦之 岡山大学, 大学病院, 講師 (50766441)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心臓突然死 / 心室細動 / Brugada症候群 / 遺伝性不整脈 / 不整脈基質 / デジタル心電情報 / デジタル心電図 / 遺伝子変異 / QT延長症候群 / 早期再分極症候群 / Ｊ波 / QRS棘波 / T波頂点-終末部間隔 / 再分極異常 / 脱分極異常 / 分裂性QRS電位 / リスクスコア

Outline of Final Research Achievements

We propose a new method to predict electrical substrate that could lead to ventricular fibrillation (VF) and sudden cardiac death (SCD). We show new risk stratification methods in Brugada syndrome. 1) Electrical substrate, such as depolarization and repolarization abnormalities, that could be determined by digital ECG data is progressive with age. 2) Methods of unmasking electrical substrate: i) Antiarrhythmic drug test could identify high-risk patients by revealing significant ST elevation and induced ventricular tachyarrhythmias. ii) patients with ventricular tachyarrhythmias at the early recovery phase of an exercise test had a risk for VF. 3) Digital ECG markers and programmed electrical stimulation: Combination of abnormal markers and programmed electrical stimulation could identify high-risk patients who had a risk for VF and adaptation of an implantable cardioveter defibrillator.

Academic Significance and Societal Importance of the Research Achievements

夜間突然死症候群の一型であるBrugada症候群は青年以降の突然死の大きな割合を占めるが、無症候例でのリスク評価は確立していない。デジタル化心電図データの異常指標から、突然死リスクの可能性のあるものを抽出可能であった。次に負荷試験などのある程度侵襲度が高い検査により、リスク例をさらに絞り込みが可能であった。抽出された高リスク群で最終的に電気生理検査を行い、植込型除細動器適応を決めることが可能であった。侵襲度・コストの小さい検査によりリスク群を抽出、順次侵襲度の高い検査の適応を決定し、高リスク群を同定することが可能となった。段階的方法により侵襲度・コスト面のバランスを考えた診療方針が決定できる。

Research Products

• [Journal Article] Improved Risk Stratification of Patients With Brugada Syndrome by the New Japanese Circulation Society Guideline ― A Multicenter Validation Study ― (2020)
  • Author(s): Wakamiya A, Kamakura T, Shinohara T, Yodogawa K, Murakoshi N, Morita H, Takahashi N, Inden Y, Shimizu W, Nogami A, Horie M, Nakajima K, Kataoka N, Wada M, Yamagata K, Ishibashi K, Inoue Y, Miyamoto K, Nagase S, Noda T, Aiba T, Yasuda S, Ieda M and Kusano K
  • Journal Title: Circulation Journal Volume: 84 Issue: 12 Pages: 2158-2165
  • DOI: 10.1253/circj.CJ-19-0910
  • NAID: 130007942469
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-11-25
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Bisoprolol Transdermal Patches for Prevention of Perioperative Myocardial Injury in High-Risk Patients Undergoing Non-Cardiac Surgery ― Multicenter Randomized Controlled Study ― (2020)
  • Author(s): Toda H, Nakamura K, Shimizu K, Ejiri K, Iwano T, Miyoshi T, Nakagawa K, Yoshida M, Watanabe A, Nishii N, Hikasa Y, Hayashi M, Morita H, Morimatsu H, Ito H; MAMACARI Investigators.
  • Journal Title: Circulation Journal Volume: 84 Issue: 4 Pages: 642-649
  • DOI: 10.1253/circj.CJ-19-0871
  • NAID: 130007815598
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-03-25
  • Peer Reviewed / Open Access
• [Journal Article] New Appearance of Fragmented QRS as a Predictor of Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy (2020)
  • Author(s): Ogura S, Nakamura K, Morita H, Toh N, Nakagawa K, Yoshida M, Watanabe A, Nishii N, Miyoshi T, Ito H.
  • Journal Title: Circulation Journal Volume: 84 Issue: 3 Pages: 487-494
  • DOI: 10.1253/circj.CJ-19-0968
  • NAID: 130007801782
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-02-25
  • Peer Reviewed / Open Access
• [Journal Article] Identification of transmembrane protein 168 mutation in familial Brugada syndrome. (2020)
  • Author(s): Shimizu A, Zankov DP, Sato A, Komeno M, Toyoda F, Yamazaki S, Makita T, Noda T, Ikawa M, Asano Y, Miyashita Y, Takashima S, Morita H, Ishikawa T, Makita N, Hitosugi M, Matsuura H, Ohno S, Horie M, Ogita H.
  • Journal Title: FASEB Journal Volume: 34 Issue: 5 Pages: 6399-6417
  • DOI: 10.1096/fj.201902991r
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significance of Exercise-Related Ventricular Arrhythmias in Patients With Brugada Syndrome (2020)
  • Author(s): Morita H, Asada ST, Miyamoto M, Morimoto Y, Kimura T, Mizuno T, Nakagawa K, Watanabe A, Nishii N and Ito H
  • Journal Title: J Am Heart Assoc Volume: 9 Issue: 23
  • DOI: 10.1161/jaha.120.016907
  • NAID: 120006951265
  • Peer Reviewed / Open Access
• [Journal Article] Long-term prognosis of patients with J-wave syndrome. (2020)
  • Author(s): Kamakura T, Shinohara T, Yodogawa K, Murakoshi N, Morita H, Takahashi N, Inden Y, Shimizu W, Nogami A, Horie M, Aiba T, Kusano K.
  • Journal Title: Heart Volume: 106 Issue: 4 Pages: 299-306
  • DOI: 10.1136/heartjnl-2019-315007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Indication and prognostic significance of programmed ventricular stimulation in asymptomatic patients with Brugada syndrome (2020)
  • Author(s): Asada Saori、Morita Hiroshi、Watanabe Atsuyuki、Nakagawa Koji、Nagase Satoshi、Miyamoto Masakazu、Morimoto Yoshimasa、Kawada Satoshi、Nishii Nobuhiro、Ito Hiroshi
  • Journal Title: EP Europace Volume: - Issue: 6 Pages: 972-979
  • DOI: 10.1093/europace/euaa003
  • Peer Reviewed / Open Access
• [Journal Article] Indication and prognostic significance of programmed ventricular stimulation in asymptomatic patients with Brugada syndrome. (2020)
  • Author(s): Asada S, Morita H, Watanabe A, Nakagawa K, Nagase S, Miyamoto M, Morimoto Y, Kawada S, Nishii N, Ito H.
  • Journal Title: Europace Volume: 4
  • Peer Reviewed
• [Journal Article] Low Consultation Rate of General Population with Atrial Fibrillation (2019)
  • Author(s): Matsumi H, Nakamura K, Eguchi E, Miyoshi T, Nakagawa K, Nishii N, Watanabe A, Ueoka A, Yoshida M, Tokunaga N, Amioka N, Yamada N, Saito D, Morita H, Ogino K, Ito H; Ibara-AF Investigators.
  • Journal Title: International Heart Journal Volume: 60 Issue: 6 Pages: 1303-1307
  • DOI: 10.1536/ihj.19-062
  • NAID: 130007753873
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2019-11-30
  • Peer Reviewed
• [Journal Article] Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients (2019)
  • Author(s): Shimizu Wataru、Makimoto Hisaki、Yamagata Kenichiro、Kamakura Tsukasa、Wada Mitsuru、Miyamoto Koji、Inoue-Yamada Yuko、Okamura Hideo、Ishibashi Kohei、Noda Takashi、Nagase Satoshi、Miyazaki Aya、Sakaguchi Heima、Shiraishi Isao、Makiyama Takeru、Ohno Seiko、Itoh Hideki、et al
  • Journal Title: JAMA Cardiology Volume: in press Issue: 3 Pages: 246-254
  • DOI: 10.1001/jamacardio.2018.4925
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Open chest epicardial mapping in an asymptomatic patient with Brugada syndrome. (2019)
  • Author(s): Watanabe A, Morita H, Kawada S, Tachibana M, Morimoto Y, Ito H.
  • Journal Title: HeartRhythm Case Rep Volume: 5 Issue: 10 Pages: 501-504
  • DOI: 10.1016/j.hrcr.2019.07.003
  • NAID: 120006844181
  • Peer Reviewed / Open Access
• [Journal Article] Successful radiofrequency catheter ablation of a premature ventricular contraction triggering ventricular fibrillation in a patient with short QT syndrome. (2019)
  • Author(s): Morimoto Y, Watanabe A, Morita H, Nishii N, Nakamura K, Ito H.
  • Journal Title: HeartRhythm Case Rep Volume: 5 Issue: 5 Pages: 262-265
  • DOI: 10.1016/j.hrcr.2019.01.012
  • Peer Reviewed / Open Access
• [Journal Article] A Low Critical Event Rate Despite a High Abnormal Event Rate in Patients with Cardiac Implantable Electric Devices Followed Up by Remote Monitoring. (2019)
  • Author(s): Morimoto Y, Nishii N, Tsukuda S, Kawada S, Miyamoto M, Miyoshi A, Nakagawa K, Watanabe A, Nakamura K, Morita H, Ito H.
  • Journal Title: Intern Med. Volume: 58 Pages: 2333-2340
  • NAID: 130007690136
  • Peer Reviewed
• [Journal Article] They Are Not Monozygotic Twins ― Long QT Syndrome Type 1 (LQT1) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) ― (2018)
  • Author(s): Morita H
  • Journal Title: Circulation Journal Volume: 82 Issue: 9 Pages: 2246-2247
  • DOI: 10.1253/circj.CJ-18-0810
  • NAID: 130007438894
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-08-24
  • Peer Reviewed
• [Journal Article] HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia (2018)
  • Author(s): Saito Y, Nakamura K, Yoshida M, Sugiyama H, Takano M, Nagase S, Morita H, Kusano KF, Ito H.
  • Journal Title: International Heart Journal Volume: 59 Issue: 3 Pages: 601-606
  • DOI: 10.1536/ihj.17-241
  • NAID: 130007378305
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2018-05-31
  • Peer Reviewed / Open Access
• [Journal Article] Shanghai Score System for Diagnosis of Brugada Syndrome: Validation of the Score System and System and Reclassification of the Patients. (2018)
  • Author(s): Kawada S, Morita H, Antzelevitch C, Morimoto Y, Nakagawa K, Watanabe A, Nishii N, Nakamura K, Ito H.
  • Journal Title: JACC Clin Electrophysiol Volume: 4 Issue: 6 Pages: 724-730
  • DOI: 10.1016/j.jacep.2018.02.009
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Progression of electrocardiographic abnormalities associated with initial ventricular fibrillation in asymptomatic patients with Brugada syndrome. (2018)
  • Author(s): Morita H, Miyamoto M, Watanabe A, Tsukuda S, Morimoto Y, Kawada S, Nakagawa K, Nishii N, Ito H.
  • Journal Title: Heart Rhythm Volume: 15 Issue: 10 Pages: 1468-1474
  • DOI: 10.1016/j.hrthm.2018.06.035
  • Peer Reviewed
• [Journal Article] A new approach for implantation of a cardiac resynchronization therapy-defibrillator in a patient with bilateral pectoral neurostimulation devices (2018)
  • Author(s): Tsukuda S, Nishii N, Inoue Y, Sasaki T, Morita H, Ito H
  • Journal Title: HeartRhythm Case Rep Volume: 4 Issue: 10 Pages: 444-446
  • DOI: 10.1016/j.hrcr.2018.06.009
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of arrhythmic events is useful to detect lead failure earlier in patients followed by remote monitoring. (2018)
  • Author(s): Nishii N, Miyoshi A, Kubo M, Miyamoto M, Morimoto Y, Kawada S, Nakagawa K, Watanabe A, Nakamura K, Morita H, Ito H.
  • Journal Title: J Cardiovasc Electrophysiol. Volume: 29 Issue: 3 Pages: 463-470
  • DOI: 10.1111/jce.13399
  • Peer Reviewed
• [Journal Article] Prognostic Significance of the Sodium Channel Blocker Test in Patients With Brugada Syndrome. (2018)
  • Author(s): Ueoka A, Morita H, Watanabe A, Morimoto Y, Kawada S, Tachibana M, Miyamoto M, Nakagawa K, Nishii N, Ito H.
  • Journal Title: J Am Heart Assoc Volume: 7 Issue: 10
  • DOI: 10.1161/jaha.118.008617
  • Peer Reviewed / Open Access
• [Journal Article] Hot topics in Brugada syndrome. (2018)
  • Author(s): Morita H
  • Journal Title: Heart Rhythm Volume: 15 Issue: 9 Pages: 1402-1403
  • DOI: 10.1016/j.hrthm.2018.04.018
  • Peer Reviewed
• [Journal Article] To pace, or not to pace in vasovagal syncope? (2018)
  • Author(s): Morita H
  • Journal Title: Trends Cardiovasc Med Volume: 28 Issue: 8 Pages: 539-540
  • DOI: 10.1016/j.tcm.2018.06.005
  • Peer Reviewed
• [Journal Article] Different responses to exercise between Andersen?Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia (2017)
  • Author(s): Inoue Yuko Y、Aiba Takeshi、Kawata Hiro、Sakaguchi Tomoko、Mitsuma Wataru、Morita Hiroshi、Noda Takashi、Takaki Hiroshi、Toyohara Keiko、Kanaya Yoshiaki、Itoi Toshiyuki、Mitsuhashi Takeshi、Sumitomo Naokata、Cho Yongkeun、Yasuda Satoshi、Kamakura Shiro、Kusano Kengo、Miyamoto Yoshihiro、Horie Minoru、Shimizu Wataru
  • Journal Title: Europace Volume: 印刷中 Issue: 10 Pages: 1675-1682
  • DOI: 10.1093/europace/eux351
  • Peer Reviewed / Open Access
• [Presentation] Brugada syndrome -Recent development of risk stratification- (2021)
  • Author(s): Morita H
  • Organizer: European Heart Rhythm Association 2021
  • Int'l Joint Research / Invited
• [Presentation] Electrophysiological characteristics of Brugada syndrome (2020)
  • Author(s): Hiroshi Morita
  • Organizer: The 84th Annual Scientific Meeting of the Japanese Circulation Society
  • Int'l Joint Research / Invited
• [Presentation] Occurrence of Ventricular Fibrillation Associated with Inherited Channelopathies in Two Patients with Congenital Heart Disease. (2019)
  • Author(s): Morimoto Y, Morita H, Tsukuda S, Kimura T, Morimoto M, Nakagawa K, Nishii N, Watanabe A, Nakamura K, Ito H.
  • Organizer: Heart Rhythm 2019
  • Int'l Joint Research
• [Presentation] Ventricular Fibrillation Induced by Non-aggressive Protocol of Programmed Electrical Stimulation Predicts Arrhythmic Events in Brugada Syndrome (2019)
  • Author(s): Kimura K, Morita H, Asada S, Morimoto Y, Miyoshi A, Miyamoto M, Nakagawa K, Nishii N, Watanabe A, Ito H.
  • Organizer: Heart Rhythm 2019
  • Int'l Joint Research
• [Presentation] Symposium: Significance of Exercise-Induced Ventricular Arrhythmias in patients with Brugada Syndrome. (2019)
  • Author(s): Morita H, Asada S, Morimoto Y, Kimura K, Miyamoto M, Miyoshi A, Nakagawa K, Nishii N, Watanabe A, Ito H.
  • Organizer: 第66回日本不整脈心電学会学術大会
• [Presentation] SY17, Genetics of Rhythm Disorders: up to date. SY17-1 Progression of an Arrhythmogenic Substrate Associated with Initial Ventricular Fibrillation Episode in Asymptomatic Patients with Brugada Syndrome. (2018)
  • Author(s): Morita H
  • Organizer: 第65回日本不整脈心電学会学術集会
• [Presentation] メディカルプロフェッショナルシンポジウム 1. 心臓イオンチャネルとイオンチャネル病. (2018)
  • Author(s): 森田 宏
  • Organizer: 第65回日本不整脈心電学会学術集会
  • Invited
• [Presentation] Topics 2 Brugada syndrome, TO2-2 Clinical Feature of Brugada syndrome patients. (2018)
  • Author(s): Morita H.
  • Organizer: The 2018 International Congress on Electrocardiology
  • Int'l Joint Research / Invited
• [Presentation] Early repolarization in Brugada syndrome. (2018)
  • Author(s): Morita H
  • Organizer: Asian Pacific Heart Rhythm Scociety 2018
  • Int'l Joint Research / Invited
• [Presentation] Inherited arrhythmia: emerging concept and gaps in knowledge. (2018)
  • Author(s): Morita H.
  • Organizer: Asian Pacific Heart Rhythm Scociety 2018
  • Int'l Joint Research / Invited
• [Presentation] Indication and prognostic significance of programmed electrical stimulation in asymptoamtic patients with Brugada syndrome. (2018)
  • Author(s): Morita H, Watanabe A, Nakagawa K, Miyamoto M, Morimoto Y, Kawada S, Nishii N, Ito H.
  • Organizer: Heart Rhythm 2018
  • Int'l Joint Research
• [Presentation] Programmed electrical stimulation can predict prognosis in asymptomatic patients but not in sympotmatic patietns with Brugada synrdome (2018)
  • Author(s): Morita H, Watanabe A, Nakagawa K, Tsukuda S, Miyamoto M, Morimoto Y, Kawada S, Nishii N, Ito H.
  • Organizer: American Heart Association Scientific Sessions 2018
  • Int'l Joint Research
• [Book] 循環器疾患最新の治療2020-2021（伊藤 浩/山下武志 編） (2020)
  • Author(s): 森田 宏
  • Total Pages: 500
  • Publisher: 南江堂
  • ISBN: 9784524249763
• [Book] 循環器専門医バイブル３ 不整脈 識る・診る・治す（小室一成 編） (2018)
  • Author(s): 川田哲史、森田 宏
  • Total Pages: 362
  • Publisher: 中山書店
  • ISBN: 9784521745855