Impact of Culprit Plaque Tissue and Microvascular Embolization on Reperfusion Injury and Development of Optimal Interventional Procedures

• Project/Area Number: 26461075
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kumamoto University
• Principal Investigator: Tsujita Kenichi 熊本大学, 大学院生命科学研究部(医), 教授 (60571263)
• 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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 冠攣縮 / 血管内超音波 / 冠動脈プラーク / 組織性状 / 再灌流障害 / 微小循環障害

Outline of Final Research Achievements

1. Verifying the feasibility and reproducibility of hyperemic microvascular resistance (hMR) in patients with healthy normal coronary arteries, the value of hMR was significantly correlated with the degree of the left ventricular hypertrophy (LVH), which has been considered to lead to microvascular dysfunction (MVD). Therefore, hMR value can be recognized as a reliable physiologic marker of MVD.
2. Coronary imaging study using IVUS/OCT demonstrated that unstable plaques containing the distal embolizing debris (e.g. lipidic tissue and necrotic　tissue) was more frequently observed in patients with ST-elevation myocardial infarction (STEMI) than in patients with non-ST-elevation MI. As the patients with STEMI experience the reperfusion injury (RI) frequently, distal embolization of culprit plaque component seems to be main reason of RI onset.
3. Thrombus aspiration was associated with reduced incidence of no reflow and slow flow during the pPCI and with the lower hMR.

Research Products

• [Journal Article] Lenvatinib, an oral multi-kinases inhibitor, -associated hypertension: Potential role of vascular endothelial dysfunction (2017)
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  • Journal Title: Atherosclerosis Volume: in press
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• [Journal Article] Identification and Assessment of Cardiac Amyloidosis by Myocardial Strain Analysis of Cardiac Magnetic Resonance Imaging (2017)
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• [Journal Article] Identification and assessment of cardiac amyloidosis by myocardial strain analysis of cardiac magnetic resonance imaging (2017)
  • Author(s): Oda S, Utsunomiya D, Nakaura T, Yuki H, Kidoh M, Morita K, Tkashio S, Yamamuro M, Izumiya Y, Hirakawa K, Ishida T, Tsujita K, Ueda M, Yamashita T, Ando Y, Hata H, Yamashita Y
  • Journal Title: Circ J Volume: in press
  • NAID: 130006887042
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Correlation between microvascular dysfunction and B-type natriuretic peptide levels in non-ischemic heart failure patients with cardiac fibrosis (2017)
  • Author(s): Hirakawa K, Yamamuro M*, Uemura T, Takashio S, Kaikita K, Utsunomiya D, Nakayama M, Yamamoto E, Yamashita Y, Hokimoto S, Tsujita K
  • Journal Title: Int J Cardiol Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reduced trans-mitral A-wave velocity predicts the presence of wild-type transthyretin amyloidosis in elderly patients with left ventricular hypertrophy (2016)
  • Author(s): Yamamura S, Izumiya Y*, Ishida T, Onoue Y, Kimura Y, Hanatani S, Araki S, Fujisue K, Sueta D, Kanazawa H, Takashio S, Usuku H, Sugamura K, Sakamoto K, Yamamoto E, Yamamuro M, Yasuda H, Kojima S, Kaikita K, Hokimoto S, Ogawa H, Tsujita K
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• [Journal Article] Helicobacter pylori Seropositivity in Patients with Interleukin-1 Polymorphisms Is Significantly Associated with ST-Segment Elevation Myocardial Infarction (2016)
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• [Journal Article] Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina (2016)
  • Author(s): Akasaka T, Sueta D, Arima Y, Tabata N, Takashio S, Izumiya Y, Yamamoto E, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Kajiwara A, Morita K, Oniki K, Saruwatari J, Nakagawa K, Ogata Y, Matsui K, Hokimoto S
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• [Journal Article] Prognostic significance of circulating leukocyte subtype counts in patients with coronary artery disease (2016)
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  • Journal Title: Atherosclerosis Volume: 255 Pages: 210-216
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Changes in the risk factors for coronary spasm (2016)
  • Author(s): Ishii M, Kaikita K*, Sato K, Yamanaga K, Miyazaki T, Akasaka T, Tabata N, Arima Y, Sueta D, Sakamoto K, Yamamoto E, Tsujita K, Yamamuro M, Kojima S, Soejima H, Hokimoto S, Matsui K, Ogawa H
  • Journal Title: IJC Heart and Vasculature Volume: 12 Pages: 85-87
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• [Journal Article] Prevalence of coronary macro- and micro-vascular dysfunctions after drug-eluting stent implantation without in-stent restenosis (2016)
  • Author(s): Hokimoto S*, Tabata N, Yamanaga K, Sueta D, Akasaka T, Tsujita K, Sakamoto K, Yamamoto E, Yamamuro M, Izumiya Y, Kaikita K, Kojima S, Matsui K, Ogawa H
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• [Journal Article] Impact of aspirin on the prognosis in patients with coronary spasm without significant atherosclerotic stenosis (2016)
  • Author(s): Ishii M, Kaikita K*, Sato K, Yamanaga K, Miyazaki T, Akasaka T, Tabata N, Arima Y, Sueta D, Sakamoto K, Yamamoto E, Tsujita K, Yamamuro M, Kojima S, Soejima H, Hokimoto S, Matsui K, Ogawa H
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• [Journal Article] Clinical and morphological presentations of acute coronary syndrome without coronary plaque rupture - An intravascular ultrasound study (2016)
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• [Journal Article] Synergistic effect of ezetimibe addition on coronary atheroma regression in patients with prior statin therapy: subanalysis of PRECISE-IVUS trial (2016)
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• [Journal Article] Lipid profile associated with coronary plaque regression in patients with acute coronary syndrome: subanalysis of PRECISE-IVUS trial (2016)
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• [Journal Article] A simple sarcopenia screening test predicts future adverse events in patients with heart failure. (2016)
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• [Journal Article] Impaired peripheral endothelial function assessed by digital reactive hyperemia peripheral arterial tonometry and risk of in-stent restenosis. (2016)
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• [Journal Article] Impact of statin therapy on clinical outcome in patients with coronary spasm. (2016)
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• [Journal Article] Clinical significance of pulse pressure in patients with heart failure with preserved left ventricular ejection fraction. (2016)
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• [Journal Article] The real-world prevalence of cardiovascular events related to coronary spasm after percutaneous coronary intervention. (2016)
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• [Journal Article] More haste, less speed: Cardiac perforation by a thoracentesis catheter. (2016)
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  • Journal Title: IJC Heart and Vasculature Volume: in press
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• [Journal Article] Gender differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder. (2016)
  • Author(s): Akasaka T, Hokimoto S*, Sueta D, Tabata N, Sakamoto K, Yamamoto E, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Kajiwara A, Morita K, Oniki K, Saruwatari J, Nakagawa K, Ogata Y, Ogawa H.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: in press
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• [Journal Article] Helicobacter Pylori-seropositivity along with Genetic and Environmental Factors Predicts Clinical Outcome after Acute Coronary Syndrome. (2016)
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  • Journal Title: Int J Cardiol Volume: 212 Pages: 54-56
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• [Journal Article] Helicobacter pylori-seropositivity along with Pro-inflammatory Interleukin-1 Polymorphisms Correlated with Myocardial Infarction. (2016)
  • Author(s): Tabata N, Hokimoto S*, Akasaka T, Sueta D, Arima Y, Sakamoto K, Yamamoto E, Izumiya Y, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Morita K, Oniki K, Saruwatari J, Nakagawa K, Yamabe H, Matsui K, Ogawa H.
  • Journal Title: Clin Trials Regul Sci Cardiol Volume: 17 Pages: 9-14
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• [Journal Article] Late gadolinium enhancement on cardiac magnetic resonance predicts coronary vasomotor abnormality and myocardial lactate production in patients with chronic heart failure. (2016)
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• [Journal Article] Total Thrombus-Formation Analysis System (T-TAS) Can Predict Periprocedural Bleeding Events in Patients Undergoing Catheter Ablation for Atrial Fibrillation. (2016)
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• [Journal Article] Assessment of platelet-derived thrombogenicity by the total thrombus-formation analysis system in coronary artery disease patients on antiplatelet therapy. (2016)
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  • Journal Title: J Thromb Haemost Volume: 14 Pages: 850-859
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• [Journal Article] Distribution of Ankle-Brachial Index among Inpatients with Cardiovascular Disease: Analysis Using the Kumamoto University Hospital Medical Database. (2016)
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• [Journal Article] New Aspects of Onco-Cardiology. (2016)
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• [Journal Article] The Clinical Significance of Plasma Neopterin in Heart Failure with Preserved Left Ventricular Ejection Fraction. (2016)
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• [Journal Article] Impact of candesartan on cardiovascular events after drug-eluting stent implantation in patients with coronary artery disease: The 4C trial. (2016)
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• [Journal Article] Clinical characteristics and intravascular ultrasound findings of culprit lesions in elderly patients with acute coronary syndrome. (2016)
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• [Journal Article] Usefulness of Excimer Laser Atherectomy for Balloon Uncrossable Lesion in Chronic Total Occlusion. (2015)
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• [Journal Article] Acetylcholine-provoked coronary spasm at site of significant organic stenosis predicts poor prognosis in patients with coronary vasospastic angina. (2015)
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• [Journal Article] Association of Estimated Central Blood Pressure Measured Non-invasively with Pulse Wave Velocity in Patients with Coronary Artery Disease. (2015)
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  • Journal Title: IJC Heart & Vasculature Volume: 8 Pages: 52-4
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• [Journal Article] Impact of esomeprazole on platelet reactivity and clinical outcome according to CYP2C19 genotype in coronary heart disease patients during dual antiplatelet therapy. (2015)
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• [Journal Article] Clinical Presentation, Management and Outcome of Japanese Patients with Acute Myocardial Infarction in the Troponin Era - Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) - (2015)
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• [Journal Article] Impact of left ventricular hypertrophy on impaired coronary microvascular dysfunction. (2015)
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• [Journal Article] Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): study protocol for a randomized controlled trial. (2015)
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• [Journal Article] Single-wire pressure and flow velocity measurement to quantify microvascular dysfunction in patients with coronary vasospastic angina. (2015)
  • Author(s): Yamanaga K, Tsujita K*, Komura N, Kaikita K, Sakamoto K, Miyazaki T, Saito M, Ishii M, Tabata N, Akasaka T, Sato K, Horio E, Arima Y, Kojima S, Tayama S, Nakamura S, Hokimoto S, Ogawa H.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 308
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• [Journal Article] Clinical characteristics and intravascular ultrasound findings of culprit lesions in elderly patients with acute coronary syndrome. (2015)
  • Author(s): Ogura Y, Tsujita K, Shimomura H, Yamanaga K, Komura N, Miyazaki T, Ishii M, Tabata N, Akasaka T, Arima Y, Sakamoto K, Kojima S, Nakamura S, Kaikita K, Hokimoto S, Ogawa H.
  • Journal Title: Heart Vessels. Volume: in press Issue: 3 Pages: 341-350
  • DOI: 10.1007/s00380-014-0616-2
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Single-wire pressure and flow velocity measurement for quantifying microvascular dysfunction in patients with coronary vasospastic angina. (2015)
  • Author(s): Yamanaga K, Tsujita K, Komura N, Kaikita K, Sakamoto K, Miyazaki T, Saito M, Ishii M, Tabata N, Akasaka T, Sato K, Horio E, Arima Y, Kojima S, Tayama S, Nakamura S, Hokimoto S, Ogawa H.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 308 Issue: 5 Pages: H478-H484
  • DOI: 10.1152/ajpheart.00593.2014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): Study protocol for a randomized controlled trial. (2015)
  • Author(s): Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, Komura N, Sakamoto K, Ono T, Oka H, Nakao K, Nakamura S, Ishihara M, Matsui K, Sakaino N, Nakamura N, Yamamoto N, Koide S, Matsumura T, Fujimoto K, Tsunoda R, Morikami Y, Matsuyama K, Oshima S, Kaikita K, Hokimoto S, Ogawa H
  • Journal Title: J Cardiol. Volume: 65 Issue: 4 Pages: 353-358
  • DOI: 10.1016/j.jjcc.2014.12.011
  • Peer Reviewed
• [Journal Article] Impact of left ventricular hypertrophy on impaired coronary microvascular dysfunction. (2015)
  • Author(s): Tsujita K, Yamanaga K, Komura N, Sakamoto K, Miyazaki T, Ishii M, Tabata N, Akasaka T, Sueta D, Arima Y, Kojima S, Yamamoto E, Yamamuro M, Tanaka T, Izumiya Y, Tayama S, Nakamura S, Kaikita K, Hokimoto S, Ogawa H.
  • Journal Title: Int J Cardiol Volume: 187 Pages: 411-413
  • DOI: 10.1016/j.ijcard.2015.03.367
  • Peer Reviewed / Open Access
• [Journal Article] Serial intravascular ultrasound assessment of very late stent thrombosis after sirolimus-eluting stent placement. (2014)
  • Author(s): Yamanaga K, Tsujita K, Shimomura H, Nakamura Y, Ogura Y, Onoue Y, Chazono N, Nagata T, Morisaki S, Kudo T, Yamada Y, Komura N, Miyazaki T, Akasaka T, Horio E, Sato K, Arima Y, Kojima S, Kaikita K, Tayama S, Hokimoto S, Ogawa H.
  • Journal Title: Journal of Cardiology Volume: 64 Issue: 4 Pages: 279-284
  • DOI: 10.1016/j.jjcc.2014.02.008
  • Peer Reviewed
• [Presentation] 冠動脈プラーク退縮におけるエゼチミブ追加治療への期待～PRECISE-IVUSトライアルからの知見～ (2017)
  • Author(s): 辻田賢一
  • Organizer: 第81回日本循環器学会総会・学術集会・Fireside Seminar1
  • Place of Presentation: 石川県立音楽堂ほか（石川県金沢市）
  • Year and Date: 2017-03-17
• [Presentation] アセチルコリン誘発冠攣縮におけるコンボワイヤーを用いた血行動態評価 (2016)
  • Author(s): 辻田賢一
  • Organizer: 第64回日本心臓病学会学術集会・ファイアーサイドシンポジウム
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-09-23
• [Presentation] 冠微小血管抵抗を加味した冠微小循環評価の試み (2016)
  • Author(s): 辻田賢一, 山永健之, 坂本憲治, 海北幸一, 掃本誠治, 小川久雄
  • Organizer: 第64回 日本心臓病学会学術集会・シンポジウム14
  • Place of Presentation: 東京
  • Year and Date: 2016-09-23
  • Invited
• [Presentation] Dual Lipid-Lowering With Ezetimibe/Statin as A Promising Anti-Atherosclerosis Strategy (2016)
  • Author(s): 辻田賢一
  • Organizer: 第80回 日本循環器学会学術集会・プレナリーセッション10
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18
  • Invited
• [Presentation] 急性冠症候群に対する積極的脂質低下療法の検討 (2015)
  • Author(s): 辻田賢一
  • Organizer: 第63回 日本心臓病学会学術集会・シンポジウム2
  • Place of Presentation: 横浜
  • Year and Date: 2015-09-18
  • Invited
• [Presentation] A Novel Promising Strategy for Plaque Regression in Pts Undergoing PCI. (2015)
  • Author(s): Tsujita K.
  • Organizer: K-Imaging (Korea Cardiovascular Interventional Imaging Forum)
  • Place of Presentation: Seoul
  • Year and Date: 2015-06-02
  • Int'l Joint Research / Invited
• [Presentation] 冠攣縮性狭心症患者における冠血管機能評価と治療戦略 (2015)
  • Author(s): 辻田賢一
  • Organizer: 第79回 日本循環器学会学術集会・会長特別企画
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
  • Invited
• [Presentation] Impact of Aging on Intravascular Ultrasound Morphology of Culprit Lesions and Clinical Characteristics in Patients with Acute Coronary Syndrome (2015)
  • Author(s): 辻田賢一
  • Organizer: ACC Science Session 2015
  • Place of Presentation: サンディエゴコンベンションセンター（サンディエゴ、米国）
  • Year and Date: 2015-03-14
• [Presentation] Impact of Left Ventricluar Hypertrophy on Impaired Coronary Microvascular Dysfunction Dtermined by Direct Single-Wire Pressure and Flow Velocity Measurement (2014)
  • Author(s): 辻田賢一
  • Organizer: AHA Science Session 2014
  • Place of Presentation: マコーミックプレイス（シカゴ、米国）
  • Year and Date: 2014-11-18
• [Presentation] 高齢発症急性冠症候群の臨床背景および責任病変血管内超音波所見の検討 (2014)
  • Author(s): 辻田 賢一
  • Organizer: 第62回日本心臓病学会学術集会
  • Place of Presentation: 仙台国際センター（仙台市青葉区）
  • Year and Date: 2014-09-26
• [Presentation] 冠攣縮性狭心症の確定診断後4年目に不安定狭心症をきたした左前下行枝器質性病変のIVUS/OCT画像の検討 (2014)
  • Author(s): 辻田賢一
  • Organizer: 第21回日本心血管インターベンション治療学会九州地方会
  • Place of Presentation: 福岡国際会議場（福岡市博多区）
  • Year and Date: 2014-08-23
• [Book] 冠動脈疾患の検査・診断 血管内超音波(IVUS),光干渉断層法(OCT) (2016)
  • Author(s): 辻田賢一*、小川久雄
  • Publisher: 日本臨牀社
• [Book] JMEDJ 治療法便覧2016 ～私の治療～ (2016)
  • Author(s): 辻田賢一*,小川久雄.
  • Publisher: 日本医事新報社
• [Book] 血管内超音波検査法(IVUS),光干渉断層法(OCT). 最新冠動脈疾患学（上）冠動脈疾患の最新治療戦略 (2016)
  • Author(s): 辻田賢一*,小川久雄.
  • Publisher: 日本臨牀社
• [Book] 「治療」96巻3月号 特集：心筋梗塞 最前線「心筋梗塞の発症因子，遺伝因子」 (2014)
  • Author(s): 辻田賢一, 海北幸一, 山永健之, 掃本誠治, 小川久雄
  • Publisher: 南山堂