Comprehensive genetic analysis in patients with idiopathic ventricular fibrillation

• Project/Area Number: 26461087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Keio University
• Principal Investigator: Aizawa Yoshiyasu 慶應義塾大学, 医学部(信濃町), 特任講師 (20528145)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 不整脈 / 遺伝子解析 / 心室細動 / 右脚ブロック / 次世代シークエンサー / ブルガダ症候群 / 心臓突然死 / 特発性心室細動 / パッチクランプ法 / 疾患特異的iPS細胞 / 突然死

Outline of Final Research Achievements

A total of 105 cases of idiopathic ventricular fibrillation were collected. There were 6 cases showing right bundle branch block. Rare variants were detected in ABCC8, CDH2, SCN3B, SCNN1B genes by the next generation sequencer. By investigating the novel genetic mutation and the mechanism of the development of ventricular fibrillation in this study, it is expected that elucidation of the pathology and tailor - made medicine for individual genotypes will be realized.

Research Products

• [Journal Article] Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles (2016)
  • Author(s): Kushiyama Y, Honjo H, Niwa R, Takanari H, Yamazaki M, Takemoto Y, Sakuma I, Kodama I, Kamiya K
  • Journal Title: American Journal of Physiology Heart and Circulatory Physiology Volume: 311 Issue: 1 Pages: 750-758
  • DOI: 10.1038/srep34198
  • NAID: 120005946586
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Novel Mechanism of Atrioventricular Block Following Transcatheter Closure of an Atrial Septal Defect. (2016)
  • Author(s): Yamamoto T, Kanazawa H, Tanosaki S, Goto S, Kimura M, Tsuruta H, Itabashi Y, Murata M, Kunitomi A, Aizawa Y, Nishiyama T, Kohno T, Maekawa Y, Takatsuki S, Sano M, Igawa O, Fukuda K.
  • Journal Title: JACC Cardiovasc Interv Volume: 9(19) Issue: 19 Pages: 2067-2069
  • DOI: 10.1016/j.jcin.2016.07.028
  • Peer Reviewed
• [Journal Article] Successful catheter ablation of an anteroseptal accessory pathway without impairing the atrioventricular conduction. (2016)
  • Author(s): Nishiyama T, Kimura T, Nishiyama N, Aizawa Y, Fukuda K, Takatsuki S.
  • Journal Title: Int J Cardiol Volume: 222 Pages: 782-4
  • DOI: 10.1016/j.ijcard.2016.08.013
  • Peer Reviewed
• [Journal Article] Report of the American Heart Association (AHA) Scientific Sessions 2015, Orlando. (2016)
  • Author(s): Aizawa Y, Kimura M, Kohno T, Fujita J, Fukuda K.
  • Journal Title: Circ J Volume: 80(1) Pages: 51-7
  • NAID: 130005117009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Report of the American Heart Association (AHA) Scientific Sessions 2015, Orlando (2016)
  • Author(s): Aizawa Y, Kimura M, Kohno T, Fujita J, Fukuda K
  • Journal Title: Circulation Journal Volume: 80 Issue: 1 Pages: 51-57
  • DOI: 10.1253/circj.CJ-15-1272
  • NAID: 130005117009
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Predictive factors of lead failure in patients implanted with cardiac devices (2015)
  • Author(s): Aizawa Y, Negishi M, Kashimura S, Nakajima K, Kunitomi A, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Fukumoto K, Tanimoto Y, Kohsaka S, Takatsuki S, Fukuda K
  • Journal Title: Int J Cardiol Volume: 199 Pages: 277-81
  • DOI: 10.1016/j.ijcard.2015.07.055
  • Acknowledgement Compliant
• [Journal Article] The Role of Circadian Rhythms in Fatal Arrhythmias and the Potential Impact of Intervention for Sleep-Disordered Breathing (2015)
  • Author(s): Aizawa Y, Kohno T, Yuasa S, Fukuda K
  • Journal Title: Curr Pharm Des Volume: 21 Pages: 3512-22
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cardiac innervation and sudden cardiac death (2015)
  • Author(s): Fukuda K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K
  • Journal Title: Circ Res Volume: 116 Issue: 12 Pages: 2005-19
  • DOI: 10.1161/circresaha.116.304679
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk factors for early replacement of cardiovascular implantable electronic devices (2015)
  • Author(s): Aizawa Y, Kunitomi A, Nakajima K, Kashimura S, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Tanimoto Y, Kohsaka S, Takatsuki S, Fukuda K
  • Journal Title: Int J Cardiol Volume: 178 Pages: 99-101
  • DOI: 10.1016/j.ijcard.2014.10.157
  • Peer Reviewed
• [Journal Article] Tachycardia-dependent augmentation of "notched J waves" in a general patient population without ventricular fibrillation or cardiac arrest: not a repolarization but a depolarization abnormality? (2015)
  • Author(s): Aizawa Y, Sato M, Kitazawa H, Aizawa Y, Takatsuki S, Oda E, Okabe M, Fukuda K
  • Journal Title: Heart Rhythm Volume: 12 Issue: 2 Pages: 376-83
  • DOI: 10.1016/j.hrthm.2014.11.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluation of differences in automated QT/QTc measurements between Fukuda Denshi and Nihon Koden systems (2014)
  • Author(s): Sano M, Aizawa Y, Katsumata Y, Nishiyama N, Takatsuki S, Kamitsuji S, Kamatani N, Fukuda K
  • Journal Title: PLoS One Volume: 9 Issue: 9 Pages: e106947-e106947
  • DOI: 10.1371/journal.pone.0106947
  • Peer Reviewed / Open Access
• [Journal Article] Electrical storm in patients with brugada syndrome is associated with early repolarization. (2014)
  • Author(s): Kaneko Y, Horie M, Niwano S, Kusano KF, Takatsuki S, Kurita T, Mitsuhashi T, Nakajima T, Irie T, Hasegawa K, Noda T, Kamakura S, Aizawa Y, Yasuoka R, Torigoe K Suzuki H, Ohe T, Shimizu A, Fukuda K, Kurabayashi M, Aizawa Y.
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: 6 Issue: 6 Pages: 1122-8
  • DOI: 10.1161/circep.114.001806
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of Rad leads to arrhythmogenesis via PKA-mediated upregulation of Ryanodine receptor activity in the heart. (2014)
  • Author(s): Yamakawa H, Murata M, Suzuki T, Yada H, Ishida H, Aizawa Y, Adachi T, Kamiya K, Fukuda K.
  • Journal Title: Biochem Biophys Res Commun Volume: 452 Issue: 3 Pages: 701-707
  • DOI: 10.1016/j.bbrc.2014.08.126
  • Peer Reviewed / Open Access
• [Journal Article] Circadian pattern of fibrillatory events in non-Brugada-type idiopathic ventricular fibrillation with a focus on J waves (2014)
  • Author(s): Aizawa Y, Sato M, Ohno S, Horie M, Takatsuki S, Fukuda K, Chinushi M, Usui T, Aonuma K, Hosaka Y, Haissaguerre M, Aizawa Y
  • Journal Title: Heart Rhythm Volume: 11 Issue: 12 Pages: 2261-6
  • DOI: 10.1016/j.hrthm.2014.08.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Genome-wide association study of electrocardiographic parameters identifies a new association for PR interval and confirms previously reported associations (2014)
  • Author(s): Sano M, Kamitsuji S, Kamatani N, Hong KW, Han BG, Kim Y, Kim JW, Aizawa Y, Fukuda K; Japan Pharmacogenomics Data Science Consortium (JPDSC)
  • Journal Title: Hum Mol Genet Volume: 174 Issue: 24 Pages: 840-2
  • DOI: 10.1093/hmg/ddu375
  • Peer Reviewed / Open Access
• [Journal Article] Thoracic impedance as a therapeutic marker of acute decompensated heart failure (2014)
  • Author(s): Aizawa Y, Takatsuki S, Kashimura S, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Tanimoto Y, Tanimoto K, Fukuda Y, Sato T, Ogawa S, Fukuda K
  • Journal Title: Int J Cardiol Volume: 174 Issue: 2 Pages: 840-2
  • DOI: 10.1016/j.ijcard.2014.04.032
  • Peer Reviewed
• [Journal Article] Clinical characteristics of atrial fibrillation detected by implanted devices and its association with ICD therapy (2014)
  • Author(s): Aizawa Y
  • Journal Title: Int J Cardiol. Volume: 172 Issue: 3 Pages: 529-30
  • DOI: 10.1016/j.ijcard.2014.01.067
  • Peer Reviewed
• [Presentation] 心臓リアノジン受容体遺伝子変異を認めたshort-coupled variant of torsade de pointes の一家系． (2016)
  • Author(s): 藤澤大志、相澤義泰、木村舞、中嶋一晶、伊藤章吾、樫村晋、國富晃、勝俣良紀、西山崇比古、木村雄弘、西山信大、福本耕太郎、谷本陽子、湯浅慎介、河野隆志、佐野元昭、高月誠司、福田恵一．
  • Organizer: 第240回 日本循環器学会関東甲信越地方会
  • Place of Presentation: ステーションコンファレンス東京（東京都千代田区）
  • Year and Date: 2016-06-04
• [Presentation] Yoshiyasu Aizawa, Mitsushige, Murata, Kazuaki Nakajima, Akira Kunitomi, Shin Kashimura, Yoshinori Katsumata, Takahiko Nishiyama, Takehiro Kimura, Nobuhiro Nishiyama, Kotaro Fukumoto, Yoko Tanimoto, Seiji Takatsuki, Keiichi Fukuda. (2016)
  • Author(s): Yoshiyasu Aizawa, Mitsushige, Murata, Kazuaki Nakajima, Akira Kunitomi, Shin Kashimura, Yoshinori Katsumata, Takahiko Nishiyama, Takehiro Kimura, Nobuhiro Nishiyama, Kotaro Fukumoto, Yoko Tanimoto, Seiji Takatsuki, Keiichi Fukuda.
  • Organizer: Heart Rhythm 2016
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2016-05-05
• [Presentation] Clinical Characteristics, and Long-term Outcome of the Dilated Phase of Hypertrophic Cardiomyopathy (2016)
  • Author(s): Yoshiyasu Aizawa, Yoko Tanimoto , Mitsushige Murata , Mai Kimura , Yoshinori Katsumata , Takahiko Nishiyama , Takehiro Kimura , Nobuhiro Nishiyama , Kotaro Fukumoto , Shinsuke Yuasa , Takashi Kohno , Shun Kohsaka , Shinji Makino , Motoaki Sano , Seiji Takatsuki , Keiichi Fukuda
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 国際センター会議棟（宮城県仙台市）
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] High Incidence of Lead Failure in Patients with Brugada Syndrome and Idiopathic Ventricular Fibrillation (2016)
  • Author(s): Yoshiyasu Aizawa, Seiji Takatsuki , Kazuaki Nakajima , Shin Kashimura , Akira Kunitomi , Yoshinori Katsumata , Takahiko Nishiyama , Takehiro Kimura , Nobuhiro Nishiyama , Kotaro Fukumoto , Yoko Tanimoto , Shun Kohsaka , Keiichi Fukuda
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 国際センター展示棟（宮城県仙台市）
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] Arrhythmogenic Right Ventricular Caridomyopathy and Brugda Syndrome; from the View of Desmosome Gene Mutation (2016)
  • Author(s): Seiko Ohno, Yoshiyasu Aizawa , Keiko Sonoda , Megumi Fukuyama , Takeru Makiyama , Kenjiro Kosaki , Keiichi Fukuda , Minoru Horie
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 国際センター会議棟（宮城県仙台市）
  • Year and Date: 2016-03-18
  • Int'l Joint Research
• [Presentation] ECG and Phenotype of Brugada Syndrome (2016)
  • Author(s): Yoshiyasu Aizawa
  • Organizer: 2016 International Forum of Ventricular Arrhythmia
  • Place of Presentation: 台北（台湾）
  • Year and Date: 2016-03-12
  • Int'l Joint Research / Invited
• [Presentation] Early Repolarization Syndrome with Electric Storm (2016)
  • Author(s): Yoshiyasu Aizawa
  • Organizer: 2016 International Forum of Ventricular Arrhythmia
  • Place of Presentation: 台北（台湾）
  • Year and Date: 2016-03-12
  • Int'l Joint Research / Invited
• [Presentation] 重症肺炎に起因する発熱によりincessant型単形性心室頻拍を発症したBrugada症候群の一例 (2015)
  • Author(s): 佐藤 由里子、相澤 義泰、宮部 彰、丸山 高、片桐 敏雄、登坂 淳、前田 備子、玉村 年健、水村 泰祐、高月 誠司、福田 恵一、杉村 洋一
  • Organizer: 第63回日本心臓病学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-09-18
  • Int'l Joint Research
• [Presentation] デバイス植込み患者における睡眠呼吸障害の合併状況と予測因子の検討 (2015)
  • Author(s): 相澤 義泰、河野 隆志、中嶋 一晶、樫村 晋、國富 晃、勝俣 良紀、西山 崇比古、木村 雄弘、西山 信大、福本 耕太郎、谷本 陽子、香坂 俊、高月 誠司、福田 恵一
  • Organizer: 第63回日本心臓病学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-09-18
  • Int'l Joint Research
• [Presentation] Comparison of circadian, weekly and seasonal Comparison of circadian, weekly and seasonal variations between electrical storms versus single VF events in patients with Brugada syndrome (2015)
  • Author(s): Yoshiyasu Aizawa, Seiji Takatsuki, Yoshinori Katsumata, Takahiko Nishiyama, Nobuhiro Nishiyama, Kotaro Fukumoto, Yoko Tanimoto, Yoshiaki Kaneko, Shinichi Niwano, Takashi Kurita, Takeshi Mitsuhashi, Takashi Noda, Shiro Kamakura, Akihiko Shimizu, Minoru Horie, Yoshifusa Aizawa, Keiichi Fukuda
  • 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
  • Place of Presentation: グランドプリンスホテル京都（京都府京都市）
  • Year and Date: 2015-07-28
  • Int'l Joint Research
• [Presentation] Sex-dependency of Sick Sinus Syndrome Phenotype in Female Members of Familial Brugada Syndrome (2015)
  • Author(s): Yoshiyasu Aizawa, Seiji Takatsuki, Seiko Ohno, Satoshi Nagase, Shogo Ito, Kazuaki Nakajima, Shin Kashimura, Akira Kunitomi, Yoshinori Katsumata, Takahiko Nishiyama, Takehiro Kimura, Nobuhiro Nishiyama, Yoko Tanimoto, Satoshi Ogawa, Kenjiro Kosaki, Keiichi Fukuda
  • Organizer: Heart Rhythm Society
  • Place of Presentation: ボストン（米国）
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] Do desmosome gene mutations cause or modify the Brugada syndrome? (2015)
  • Author(s): Seiko Ono, Yoshiyasu Aizawa, Megumi Fukuyama, Takeru Makiyama, Kenjiro Kosaki, Keiichi Fukuda, Minoru Horie
  • Organizer: Heart Rhythm Society
  • Place of Presentation: ボストン（米国）
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] 当院で発生した植込みデバイスのリード不全発生症例の臨床的特徴 (2015)
  • Author(s): 相澤義泰、根岸壮親、西山愛光、上岡天湖、中嶋一晶、樫村晋、國富晃、勝俣良紀、西山崇比古、木村雄弘、西山信大、谷本陽子、香坂俊、高月誠司、福田恵一
  • Organizer: 第7回植込みデバイス関連冬季大会
  • Place of Presentation: 東京都、東京プリンスホテル
  • Year and Date: 2015-02-21
• [Presentation] VF再発およびelectrical stormを呈するBrugada症候群・特発性心室細動症例の臨床的特徴 (2015)
  • Author(s): 伊藤章吾、相澤義泰、中嶋一晶、樫村晋、國富晃、勝俣良紀、西山崇比古、木村雄弘、西山信大、福本耕太郎、谷本陽子、高月誠司、福田恵一
  • Organizer: 第13回 特発性心室細動研究会
  • Place of Presentation: 東京都、大手町サンケイプラザ
  • Year and Date: 2015-02-14
• [Presentation] ラミンA/C変異を認めた家族性洞不全症候群の1例 (2015)
  • Author(s): 中嶋一晶, 相澤義泰, 伊藤章吾, 樫村晋, 國富晃, 勝俣良紀, 西山崇比古, 木村雄弘, 西山信大, 谷本陽子, 湯浅槙介, 小崎健次郎, 福田恵一, 高月誠司
  • Organizer: 第27回臨床不整脈研究会
  • Place of Presentation: 東京都港区、東京コンファレンスセンター
  • Year and Date: 2015-01-10
• [Presentation] 植込みデバイスのジェネレータ交換頻度に寄与する臨床的指標の検討 (2014)
  • Author(s): 相澤義泰、高月誠司、樫村晋、勝俣良紀、西山崇比古、木村雄弘、西山信大、谷本陽子、谷本耕司郎、香坂俊、福田恵一
  • Organizer: 第62回日本心臓病学会学術集会
  • Place of Presentation: 宮城県、仙台国際センター
  • Year and Date: 2014-09-26
• [Presentation] RyR2 Mutation may Underlie a Short-coupled Variant of Torsade de Pointes (2014)
  • Author(s): Yoshiyasu Aizawa, Seiji Takatsuki, Shin Kashimura, Takahiko Nishiyama, Yoshinori Katsumata, Takehiro Kimura, Nobuhiro Nishiyama, Yoko Tanimoto, Kojiro Tanimoto, Hideo Mitamura, Kenjiro Kosaki, Keiichi Fukuda
  • Organizer: Heart Rhythm
  • Place of Presentation: 米国サンフランシスコ、moscone convention center
  • Year and Date: 2014-05-08
• [Book] ブルガダ症候群と突然死の関係は? (2016)
  • Author(s): 相澤義泰, 福田恵一.
  • Publisher: 日本医事新報
• [Book] 慶應循環器内科カンファレンス(第58回) 偽腱索を有する左室起源特発性心室頻拍に対してカテーテルアブレーションを行った一例. (2016)
  • Author(s): 相澤義泰.
  • Publisher: 月刊レジデント
• [Book] 4あいまいなBrugada波形を浮き立たせる エキスパートはここを見る 心電図読み方の極意． (2016)
  • Author(s): 相澤義泰.
  • Publisher: 南山堂．
• [Book] 【心電図が臨床につながる本。】(II章)波形からみた心電図 心臓の器質的疾患Plus QRSの異常 QRS幅の延長. (2016)
  • Author(s): 相澤義泰, 倉田奈緒美.
  • Publisher: 臨床検査
• [Book] 不整脈症候群-遺伝子変異から不整脈治療を捉える (2015)
  • Author(s): 相澤義泰、佐野元昭
  • Total Pages: 196
  • Publisher: 南江堂