A Novel Risk Predictive Model Construction of Sudden Cardiac Death in Patients with Brugada Syndrome

• Project/Area Number: 17K09501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Hiroshima University
• Principal Investigator: Nakano Yukiko 広島大学, 医系科学研究科(医), 准教授 (10397911)
• Co-Investigator(Kenkyū-buntansha): 越智 秀典 広島大学, 医歯薬保健学研究科(医), 講師 (10415119)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ブルガダ症候群 / 心臓突然死 / リスク予測 / 突然死 / rJ interval / リスク層別化 / 心室細動 / リスクモデル / リスク評価 / 内科

Outline of Final Research Achievements

We enrolled 575 Brugada syndrome (BrS) patients from 9 institutions, and evaluated association between VF occurrence and non-invasive parameters. The VF events occurred in 18 patients (3.8%) of the 469 BrS patients without VF history during mean 5.8 years follow up period. Using multivariate analysis, syncope episode (77.8% v.s. 24.6%, p<0.0001) and longer r-J interval (108.2±14.0ms v.s. 95.6±15.4ms, p=0.0025) were independent predictors of new onset VF in patients without VF history. The area under curve was 0.858 in ROC analysis of logistic model using these 2 parameters.

Academic Significance and Societal Importance of the Research Achievements

今回我々は、初めて心室細動の既往のないブルガダ症候群患者では失神およびV1誘導でのr-J interval が独立した予後予測因子であり、両者を用いたロジスティックモデルは高い予後予測能を有することを示した。これまで心室細動の既往のない症例のリスクの層別化の方法は報告されておらず、植込み型除細動器植込みが必要な症例の適切な選択により、突然死の予防、および不必要な植込みによる患者さんのQOL低下の予防という点や、医療経済的にも非常に意義深い。

Research Products

• [Journal Article] Predicting atrial fibrillation using a combination of genetic risk score and clinical risk factors. (2020)
  • Author(s): Okubo Y, Nakano Y, Ochi H, Onohara Y, Tokuyama T, Motoda C, Amioka M, Hironobe N, Okamura S, Ikeuchi Y, Miyauchi S, Chayama K, Kihara Y.
  • Journal Title: Heart Rhythm. Volume: 20 Issue: 5 Pages: 699-705
  • DOI: 10.1016/j.hrthm.2020.01.006
• [Journal Article] Ser96Ala genetic variant of the human histidine-rich calcium-binding protein is a genetic predictor of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation. (2019)
  • Author(s): Amioka M, Nakano Y, Ochi H, Onohara Y, Sairaku A, Tokuyama T, Motoda C, Matsumura H, Tomomori S, Hironobe N, Okubo Y, Okamura S, Chayama K, Kihara Y.
  • Journal Title: PLoS One Volume: 6 Issue: 3 Pages: e0213208-e0213208
  • DOI: 10.1371/journal.pone.0213208
  • Peer Reviewed
• [Journal Article] Diagnostic performance of the N-terminal pro-brain natriuretic peptide to detect an increased left atrial pressure in patients with persistent atrial fibrillation (2018)
  • Author(s): Amioka Michitaka、Sairaku Akinori、Nakano Yukiko、Tokuyama Takehito、Matsumura Hiroya、Tomomori Shunsuke、Hironobe Naoya、Kihara Yasuki
  • Journal Title: Clinical Chemistry and Laboratory Medicine (CCLM) Volume: 56 Issue: 6 Pages: e147-e149
  • DOI: 10.1515/cclm-2017-0903
  • Peer Reviewed / Open Access
• [Journal Article] Effect of fibrillatory wave amplitude on coronary blood flow as assessed by thrombolysis in myocardial infarction frame count in patients with atrial fibrillation (2018)
  • Author(s): Sumimoto Yoji、Kurisu Satoshi、Hitta Kazuhiro、Ikenaga Hiroki、Ishibashi Ken、Fukuda Yukihiro、Nakano Yukiko、Kihara Yasuki
  • Journal Title: Heart and Vessels Volume: 印刷中 Issue: 7 Pages: 786-792
  • DOI: 10.1007/s00380-018-1121-9
  • Peer Reviewed
• [Journal Article] Head-to-head comparison of the heart rate variability between the bisoprolol transdermal patch and bisoprolol fumarate tablet (2018)
  • Author(s): Sairaku Akinori、Nakano Yukiko、Shiode Nobuo、Suenari Kazuyoshi、Oda Nozomu、Ono Koichi、Kihara Yasuki
  • Journal Title: Cardiovascular Therapeutics Volume: 印刷中 Issue: 3
  • DOI: 10.1111/1755-5922.12325
  • Peer Reviewed / Open Access
• [Journal Article] Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension (2018)
  • Author(s): Kajikawa M, Maruhashi T, Hidaka T, Nakano Y, Kurisu S, Matsumoto T, Iwamoto Y, Kishimoto S, Matsui S, Aibara Y, Yusoff FM, Kihara Y, Chayama K, Goto C, Noma K, Nakashima A, Watanabe T, Tone H, Hibi M, Osaki N, Katsuragi Y, Higashi Y
  • Journal Title: European Journal of Nutrition Volume: 印刷中 Issue: 3 Pages: 1611-1617
  • DOI: 10.1007/s00394-018-1611-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In Paroxysmal Atrial Fibrillation Patients, the Neutrophil-to-lymphocyte Ratio Is Related to Thrombogenesis and More Closely Associated with Left Atrial Appendage Contraction than with the Left Atrial Body Function (2018)
  • Author(s): Fukuda Y, Okamoto M, Tomomori S, Matsumura H, Tokuyama T, Nakano Y, Kihara Y.
  • Journal Title: Internal Medicine Volume: 57 Issue: 5 Pages: 633-640
  • DOI: 10.2169/internalmedicine.9243-17
  • NAID: 130006407669
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] HCN4 Gene Polymorphisms Are Associated With Occurrence of Tachycardia-Induced Cardiomyopathy in Patients With Atrial Fibrillation (2018)
  • Author(s): Nakano Yukiko、Ochi Hidenori、Sairaku Akinori、Onohara Yuko、Tokuyama Takehito、Motoda Chikaaki、Matsumura Hiroya、Tomomori Shunsuke、Amioka Michitaka、Hironobe Naoya、Ohkubo Yousaku、Okamura Shou、Makita Naomasa、Yoshida Yukihiko、Chayama Kazuaki、Kihara Yasuki
  • Journal Title: Circulation: Genomic and Precision Medicine Volume: 11 Issue: 7 Pages: 1-7
  • DOI: 10.1161/circgen.117.001980
  • Peer Reviewed
• [Journal Article] Maintenance of low inflammation level by the ZFHX3 SNP rs2106261 minor allele contributes to reduced atrial fibrillation recurrence after pulmonary vein isolation (2018)
  • Author(s): Tomomori Shunsuke、Nakano Yukiko、Ochi Hidenori、Onohara Yuko、Sairaku Akinori、Tokuyama Takehito、Motoda Chikaaki、Matsumura Hiroya、Amioka Michitaka、Hironobe Naoya、Ookubo Yousaku、Okamura Shou、Kawazoe Hiroshi、Chayama Kazuaki、Kihara Yasuki
  • Journal Title: PLOS ONE Volume: 13 Issue: 9 Pages: e0203281-e0203281
  • DOI: 10.1371/journal.pone.0203281
• [Journal Article] Chromosomal Abnormalities in Human Lymphocytes after Computed Tomography Scan Procedure (2018)
  • Author(s): Shi L, Fujioka K, Sakurai-Ozato N, Fukumoto W, Satoh K, Sun J, Awazu A, Tanaka K, Ishida M, Ishida T, Nakano Y, Kihara Y, Hayes CN, Aikata H, Chayama K, Ito T, Awai K, Tashiro S
  • Journal Title: Radiation Research Volume: 190 Issue: 4 Pages: 424-432
  • DOI: 10.1667/rr14976.1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chromosome 4q25 Variant rs6817105 Bring Sinus Node Dysfunction and Left Atrial Enlargement (2018)
  • Author(s): Tomomori Shunsuke、Nakano Yukiko、Ochi Hidenori、Onohara Yuko、Sairaku Akinori、Tokuyama Takehito、Motoda Chikaaki、Matsumura Hiroya、Amioka Michitaka、Hironobe Naoya、Okubo Yousaku、Okamura Shou、Kawazoe Hiroshi、Nishiyama Yukie、Tahara Hidetoshi、Chayama Kazuaki、Kihara Yasuki
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-6
  • DOI: 10.1038/s41598-018-32453-8
• [Presentation] Brugada症候群の心臓突然死リスク予測モデルを用いたリスク階層化中間報告 (2019)
  • Author(s): 中野由紀子
  • Organizer: 心臓病学会
  • Invited
• [Presentation] Role of microRNA in genetic regulation of cardiac arrhythmias. (2019)
  • Author(s): Nakano Y
  • Organizer: APHRS2019 Asia Pacific Heart Rhythm Society
• [Presentation] Genetic Risk Prediction of AF (2018)
  • Author(s): Nakano Y
  • Organizer: APHRS
  • Int'l Joint Research / Invited
• [Presentation] Genetics of Tachycardia-Induced Cardiomyopathy (2018)
  • Author(s): Nakano Y
  • Organizer: APHRS
  • Int'l Joint Research / Invited
• [Presentation] Ser96Ala Genetic Variant of Human Histidine-rich Calcium-binding Protein is a Genetic Predictor of Recurrence after Catheter Ablation in Patients with Paroxysmal Atrial Fibrillation (2018)
  • Author(s): Amioka M, Nakano Y, Sairaku A, Tokuyama T, Motoda C, Matsumura H, Tomomori S, Hironobe N, Okubo Y, Okamura S, Chayama K, Kihara Y.
  • Organizer: APHRS
  • Int'l Joint Research
• [Presentation] Persistant Atrial Fibrillation and Diabetesare Independent Predictors of Tachycardia Induced Cardiomyopathy in Patients with Atrial Fibrillarion (2018)
  • Author(s): Hironobe N, Nakano Y, Okamura S, Okubo Y, Amioka M, Motoda C, Tokuyama T, Kihara Y
  • Organizer: APHRS
  • Int'l Joint Research
• [Presentation] Increased Urinary Liver-Type Fatty Acid-Binding Protein Level Predicts Major Adverse Cardiovascular Events in Hypertensive Patients (2018)
  • Author(s): Okubo Y, Nakano Y, Miyauchi S, Okamura S, Hironobe N, Amioka M, Motoda C, Tokuyama T, Kihara Y
  • Organizer: American Heart Association Scientific Sessions
  • Int'l Joint Research
• [Presentation] Plasma Micrornas as NonInvasive Biomarkers in Patients With Brugada Syndrome (2018)
  • Author(s): Nakano Y, Nishiyama Y, Onohara Y, Tokuyama T, Motoda C, Amioka M, Hironobe N, Okubo Y, Okamura S, Miyauchi S, Tahara H, Kihara Y
  • Organizer: American Heart Association Scientific Sessions
  • Int'l Joint Research
• [Presentation] Leucocyte Telomere G-Tail Length Is Shortened In Patients With Atrial Fibrillation. (2018)
  • Author(s): Miyauchi S, Nakano Y, Okamura S, Okubo Y, Hironobe Y, Amioka M, Motoda C, Tokuyama T, Kihara Y.
  • Organizer: American Heart Association Scientific Sessions
  • Int'l Joint Research
• [Presentation] Prediction of Atrial Fibrillation using Combination of Genetic Risk Score and Clinical Risk Factors (2018)
  • Author(s): Okubo Y, Nakano Y, Miyauchi S, Okamura S, Hironobe N, Amioka M, Motoda C, Tokuyama T, Kihara Y
  • Organizer: American Heart Association Scientific Sessions
  • Int'l Joint Research
• [Presentation] HCN4 Gene Polymorphisms Are Associated With the Occurrence of Tachycardia Induced Cardiomyopathy in Patients With Atrial Fibrillation. (2018)
  • Author(s): Nakano Y, Ochi H, Onohara Y, Tokuyama T, Motoda C, Amioka M, Hironobe N, Okubo Y, Miyauchi S, Tomomori S, Matsumura H, Sairaku A, Chayama K, Kihara YNakano Y, Ochi H, Onohara Y, Tokuyama T, Motoda C, Amioka M, Hironobe N, Okubo Y, Miyauchi S, Tomomori S, Matsumura H, Sairaku A, Chayama K, Kihara Y
  • Organizer: American Heart Association Scientific Sessions
  • Int'l Joint Research
• [Presentation] A common SCN10A variant may contribute to decrease SCN5A expression by promoting SCN5A promoter methylation in Brugada syndrome patients (2018)
  • Author(s): Okamura S, Nakano Y, Okubo Y, Hironobe N, Amioka M, Tomomori S, Matsumura H, Motoda C, Tokuyama T, Sairaku A, Kihara Y.
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Studying Progressive Cardiac Conduction Disturbance with patient-specific iPSCs (2018)
  • Author(s): Motoda C, Nakano Y, Kihara Y, et al
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Semaphorin 3A Polymorphism Modifies Autonomic Function in Brugada Syndrome (2018)
  • Author(s): Tokuyama T, Nakano Y, Okamura S, Okubo Y, Hironobe N, Amioka M, Tomomori S, Matsumura H, Motoda C, Sairaku A, Kihara Y
  • Organizer: 第82回日本循環器学会学術集会