2015 Fiscal Year Research-status Report
再灌流障害における責任冠動脈粥腫性状および微小循環障害の関与と至適治療戦略の開発
| Project/Area Number |
26461075
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| Research Institution | Kumamoto University |
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Principal Investigator |
辻田 賢一 熊本大学, その他の研究科, 講師 (60571263)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 再灌流障害 / 微小循環障害 / 冠動脈プラーク |
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| Outline of Annual Research Achievements |
1.対象患者（急性心筋梗塞を発症し当科緊急入院し、心臓カテーテル検査において血管造影上の責任冠動脈病変が同定され、同部位に対する直接的冠動脈インターベンション（PPCI）を施行する患者のうち、本研究参加への同意が得られた患者）の登録を行った。2.PPCI施行時における血管内超音波（IVUS）および光干渉断層法（OCT）による冠動脈プラーク組織性状評価法の施行を行った。この結果をもとに、急性冠症候群の中でもST上昇型心筋梗塞患者の責任冠動脈プラークに脂質成分など不安定プラーク要素が多いこと(Tak
aoka N, Tsujita K, et al. Int J Cardiol 2014;171:423-430 (Corresponding author))を報告した。本研究においても、PPCI施行時にIVUSおよびOCTを施行し、責任冠動脈プラーク組織性状評価を施行した。3.PPCI施行時におけるMVD評価：ComboWireデータに基づくHMR算出を施行した。我々はまずこのComboWireデータの信頼性を確認するため冠動脈病変を有さない患者群において、データを蓄積し、HMRが冠微小循環障害をヒト体内において信頼性をもって評価可能であること、また冠攣縮性狭心症(Yamanaga K, Tsujita K, et al. Am J Physiol Heart Circ Physiol 2015;308:H478-84 (Corresponding author))や左室肥大(Tsujita K, Yamanaga K, et al. Int J Cardiol 2015;187:411-413 (Corresponding author))などの病態において、この冠微小循環抵抗が増加していることを報告した。4.コアラボでの定量的IVUS画像解析を施行した。5.確認造影時におけるMVD再評価を上記登録患者のうち確認造影施行患者において施行した。6.経時的心エコーによる心機能評価を上記登録患者のうち確認造影施行患者において施行した。
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
交付申請書に記載した「研究の目的」「研究計画」の則り、平成26年度は、1.対象患者の登録；2.PPCI施行時におけるIVUSおよびOCTによる冠動脈プラーク組織性状評価法の施行；3.PPCI施行時におけるMVD評価：ComboWireデータに基づくHMR算出を施行；4.コアラボでの定量的IVUS画像解析を施行；5.確認造影時におけるMVD再評価を上記登録患者のうち確認造影施行患者において施行；6.経時的心エコーによる心機能評価を上記登録患者のうち確認造影施行患者において施行、に関しては予定どおり施行することができた。
また、上記達成項目をクリアーすることができた研究成果については、上記実績概要の通り、国際ジャーナルに報告した。
従って、本研究の達成状況はおおむね研究計画書通り進行していると思われる。
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| Strategy for Future Research Activity |
当初の研究計画書の則り、平成27年度以降も予定通りの計画遂行が可能と思われる。具体的には、
１．RI発生の原因となりうるプラーク内容物末梢塞栓の予防的治療戦略開発
現段階で、RI発生を軽減させうるPPCIにおける治療手技は確立していないため、本研究では、RIによるMVD発生予防目的の至適治療戦略開発に向け、血栓・末梢塞栓物質捕捉カテーテルであるFILTRAP®(上図)によるPPCI前治療の有用性評価を行う。具体的には
、PPCIを施行する急性心筋梗塞患者のうち、本研究参加に同意を得た患者において、①従来治療である現行ガイドラインに則った一般的PPCI治療手技群と②FILTRAP®前治療追加群、に無作為割り付けし、責任冠動脈プラーク評価ならびにMVD、心機能評価を両群で行うことで、FILTRAP®によるPPCI前治療のRI発生予防効果を検討し、その長期的な有用性評価についても経時的心エコー評価にて行う。
２．フォローアップ症例におけるMVD改善・増悪の予後規定因子の探索
これまで、MVD改善に有用性が証明された薬理学的介入手法としては、ニコランジル(シグマート®)が挙げられ我々は報告しているが(Izumiya, et al. Atherosclerosis 2011)、そのほか急性心筋梗塞患者におけるMVDの増悪、改善の予後規定因子は明らかになっていないため、本研究では、確認造影時のMVD再評価データを用いて、PPCI施行時のMVDデータと比較し、各々の臨床背景因子や処方薬、PPCI治療手技などを従属因子とし単変量・多変量解析を行うことで、急性心筋梗塞患者におけるMVD改善・増悪の予後規定因子の探索を行う。本解析で、急性心筋梗塞患者におけるMVD改善・増悪の予後規定因子が明らかになれば、急性心筋梗塞患者に対する至適治療戦略の開発に資する重要な臨床データが得られると期待される。
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| Causes of Carryover |
登録患者数がわずかに目標に達せず、次年度の登録患者数達成を待って、使用物品の購入を次年度にまとめて行う方が効率が良かった
ため（医療機器の使用期限などがあり、本年度購入は物品の使用が間に合わず無駄になってしまう可能性が生じた）。
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| Expenditure Plan for Carryover Budget |
上記の通り、次年度の物品購入の上、各種冠動脈プラーク形態評価および冠微小循環障害マーカー測定を行う計画とした。
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[Journal Article] A simple sarcopenia screening test predicts future adverse events in patients with heart failure.2016
Author(s)
Onoue Y, Izumiya Y*, Hanatani S, Tanaka T, Yamamura S, Kimura Y, Araki S, Sakamoto K, Tsujita K, Yamamoto E, Yamamuro M, Kojima S, Kaikita K, Hokimoto S.
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Journal Title
Int J Cardiol.
Volume: 215
Pages: 301-306
Peer Reviewed / Open Access
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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
Author(s)
Komura N, Tsujita K*, Yamanaga K, Sakamoto K, Kaikita K, Hokimoto S, Iwashita S, Miyazaki T, Akasaka T, Arima Y, Yamamoto E, Izumiya Y, Yamamuro M, Kojima S, Tayama S, Sugiyama S, Matsui K, Nakamura S, Hibi K, Kimura K, Umemura S, Ogawa H.
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Journal Title
J Am Heart Assoc
Volume: in press
Pages: in press
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Impact of statin therapy on clinical outcome in patients with 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.
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Journal Title
J Am Heart Assoc.
Volume: in press
Pages: in press
Peer Reviewed / Open Access
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[Journal Article] Clinical significance of pulse pressure in patients with heart failure with preserved left ventricular ejection fraction.2016
Author(s)
Tokitsu T, Yamamoto E*, Hirata Y, Kusaka H, Fujisue K, Sueta D, Sugamura K, Sakamoto K, Tsujita K, Kaikita K, Hokimoto S, Sugiyama S, Ogawa H.
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Journal Title
Eur J Heart Fail
Volume: in press
Pages: in press
Peer Reviewed / Open Access
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[Journal Article] More haste, less speed: Cardiac perforation by a thoracentesis catheter.2016
Author(s)
Sueta D, Hokimoto S*, Okamoto K, Yasuda H, Usuku H, Tazume H, Yamamoto E, Sakamoto K, Izumiya Y, Tsujita K, Kaikita K, Sakaguchi H, Fukui T, Ogawa H.
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Journal Title
IJC Heart and Vasculature
Volume: in press
Pages: in press
Peer Reviewed / Open Access
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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.
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Journal Title
Am J Physiol Heart Circ Physiol
Volume: in press
Pages: in press
Peer Reviewed / Open Access
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[Journal Article] Helicobacter Pylori-seropositivity along with Genetic and Environmental Factors Predicts Clinical Outcome after Acute Coronary Syndrome.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, Ogawa H.
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Journal Title
Int J Cardiol
Volume: 212
Pages: 54-56
Peer Reviewed / Open Access
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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.
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Journal Title
Clin Trials Regul Sci Cardiol
Volume: 17
Pages: 9-14
Peer Reviewed / Open Access
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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
Author(s)
Uemura T, Yamamuro M*, Kaikita K, Takashio S, Utsunomiya D, Hirakawa K, Nakayama M, Sakamoto K, Yamamoto E, Tsujita K, Kojima S, Hokimoto S, Yamashita Y, Ogawa H.
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Journal Title
Heart Vessels.
Volume: in press
Pages: in press
Peer Reviewed / Open Access
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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
Author(s)
Ito M, Kaikita K*, Sueta D, Ishii M, Oimatsu Y, Arima Y, Iwashita S, Takahashi A, Hoshiyama T, Kanazawa H, Sakamoto K, Yamamoto E, Tsujita K, Yamamuro M, Kojima S, Hokimoto S, Yamabe H, Ogawa H.
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Journal Title
J Am Heart Assoc.
Volume: 5
Pages: e002744
DOI
Peer Reviewed / Open Access
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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
Author(s)
Arima Y, Kaikita K*, Ishii M, Ito M, Sueta D, Oimatsu Y, Sakamoto K, Tsujita K, Kojima S, Nakagawa K, Hokimoto S, Ogawa H.
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Journal Title
J Thromb Haemost
Volume: 14
Pages: 850-859
Peer Reviewed / Open Access
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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
Author(s)
Hokimoto S*, Soejima H, Kojima S, Kaikita K, Yamamuro M, Izumiya Y, Tsujita K, Yamamoto E, Tanaka T, Sugamura K, Arima Y, Sakamoto K, Akasaka T, Tabata N, Sueta D, Miyoshi I, Usami M, Ogawa H.
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Journal Title
Ann Vasc Dis
Volume: 9
Pages: 22-29
Peer Reviewed / Open Access
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[Journal Article] The Clinical Significance of Plasma Neopterin in Heart Failure with Preserved Left Ventricular Ejection Fraction.2016
Author(s)
Yamamoto E*, Hirata Y, Tokitsu T, Kusaka H, Tabata N, Tsujita K, Yamamuro M, Kaikita K, Watanabe H, Hokimoto S, Maruyama T, Ogawa H.
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Journal Title
ESC Heart Failure
Volume: 3
Pages: 53-59
Peer Reviewed / Open Access
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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
Author(s)
Sakamoto T*, Ogawa H, Nakao K, Hokimoto S, Tsujita K, Koide S, Yamamoto N, Shimomura H, Matsumura T, Oshima S, Kikuta K, Oka H, Kimura K, Matsui K; 4C (Candesartan for Prevention of Cardiovascular Events after CYPHER™ or TAXUS™ Coronary Stenting) study investigators.
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Journal Title
J Cardiol
Volume: 67
Pages: 371-7
Peer Reviewed / Open Access
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[Journal Article] Differential impact of peripheral endothelial dysfunction on subsequent cardiovascular events following percutaneous coronary intervention between chronic kidney disease (CKD) and non-CKD patients.2016
Author(s)
Tabata N, Hokimoto S*, Akasaka T, Arima Y, Sakamoto K, Yamamoto E, Tsujita K, Izumiya Y, Yamamuro M, Kojima S, Kaikita K, Ogawa H.
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Journal Title
Heart Vessels
Volume: in press
Pages: in press
Peer Reviewed / Open Access
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[Journal Article] Clinical characteristics and intravascular ultrasound findings of culprit lesions in elderly patients with acute coronary syndrome.2016
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.
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Journal Title
Heart Vessels
Volume: 31
Pages: 341-350
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Determinants of Myocardial Lactate Production During Acetylcholine Provocation Test in Patients with Coronary Spasm.2015
Author(s)
Kaikita K*, Ishii M, Sato K, Nakayama M, Arima Y, Tanaka T, Sugamura K, Sakamoto K, Izumiya Y, Yamamoto E, Tsujita K, Yamamuro M, Kojima S, Soejima H, Hokimoto S, Matsui K, Ogawa H.
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Journal Title
J Am Heart Assoc.
Volume: 4
Pages: e002387
DOI
Peer Reviewed / Open Access
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[Journal Article] Prognostic Significance of Peripheral Microvascular Endothelial Dysfunction in Heart Failure With Reduced Left Ventricular Ejection Fraction.2015
Author(s)
Fujisue K, Sugiyama S*, Matsuzawa Y, Akiyama E, Sugamura K, Matsubara J, Kurokawa H, Maeda H, Hirata Y, Kusaka H, Yamamoto E, Iwashita S, Sumida H, Sakamoto K, Tsujita K, Kaikita K, Hokimoto S, Matsui K, Ogawa H.
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Journal Title
Circ J.
Volume: 79
Pages: 2623-31
Peer Reviewed / Open Access
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[Journal Article] Nocturia in Patients With Sleep-Disordered Breathing and Cardiovascular Disease.2015
Author(s)
Miyazaki T, Kojima S*, Yamamuro M, Sakamoto K, Izumiya Y, Tsujita K, Yamamoto E, Tanaka T, Kaikita K, Hokimoto S, Ogawa H.
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Journal Title
Circ J.
Volume: 79
Pages: 2632-40
Peer Reviewed / Open Access
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[Journal Article] Clinical significance of plasma galectin-3 in patients with coronary artery disease.2015
Author(s)
Kusaka H, Yamamoto E*, Hirata Y, Fujisue K, Tokitsu T, Sugamura K, Sakamoto K, Tsujita K, Kaikita K, Hokimoto S, Sugiyama S, Ogawa H.
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Journal Title
Int J Cardiol.
Volume: 201
Pages: 532-534
Peer Reviewed / Open Access
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[Journal Article] Physiological basis of discordance between coronary flow velocity reserve and hyperemic microvascular resistance for evaluating coronary microvascular dysfunction in patients without atherosclerotic obstruction.2015
Author(s)
Yamanaga K, Tsujita K*, Komura N, Kaikita K, Sakamoto K, Miyazaki T, Saito M, Ishii M, Tabata N, Akasaka T, Arima Y, Yamamoto E, Yamamuro M, Izumiya Y, Kojima S, Tayama S, Nakamura S, Hokimoto S, Ogawa H.
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Journal Title
Int J Cardiol.
Volume: 201
Pages: 535-537
Peer Reviewed / Open Access / Acknowledgement Compliant
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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
Author(s)
Ishii M, Kaikita K*, Sato K, Tanaka T, Sugamura K, Sakamoto K, Izumiya Y, Yamamoto E, Tsujita K, Yamamuro M, Kojima S, Soejima H, Hokimoto S, Matsui K, Ogawa H.
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Journal Title
J Am Coll Cardiol
Volume: 66
Pages: 1105-1115
Peer Reviewed / Open Access
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[Journal Article] Impact of dual lipid-lowering strategy with ezetimibe and atorvastatin on coronary plaque regression in patients with percutaneous coronary intervention. Insights from the multicenter randomized controlled PRECISE-IVUS trial.2015
Author(s)
Tsujita K*, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, Komura N, Sakamoto K, 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。
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Journal Title
J Am Coll Cardiol
Volume: 66
Pages: 495-507
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Overview of the 79th Annual Scientific Meeting of the Japanese Circulation Society - Late-Breaking Cardiovascular Medicine From Japan.2015
Author(s)
Hokimoto S*, Yasuda S, Sueta D, Tsujita K, Sakamoto K, Yamamuro M, Izumiya Y, Arima Y, Usuku H, Sumida Y, Kojima S, Kaikita K, Kanazawa H, Yamabe H, Ogawa H.
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Journal Title
Circ J
Volume: 79
Pages: 1675-9
Peer Reviewed / Open Access
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[Journal Article] Relationship between inter-arm blood pressure differences and future cardiovascular events in coronary artery disease.2015
Author(s)
Tokitsu T, Yamamoto E*, Hirata Y, Fujisue K, Sugamura K, Maeda H, Tsujita K, Kaikita K, Hokimoto S, Sugiyama S, Ogawa H.
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Journal Title
J Hypertens
Volume: 33
Pages: 1780-90
Peer Reviewed / Open Access
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[Journal Article] The pivotal role of a novel biomarker of reactive oxygen species in chronic kidney disease.2015
Author(s)
Hirata Y, Yamamoto E*, Tokitsu T, Fujisue K, Kurokawa H, Sugamura K, Sakamoto K, Tsujita K, Tanaka T, Kaikita K, Hokimoto S, Sugiyama S, Ogawa H.
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Journal Title
Medicine
Volume: 94
Pages: e1040
Peer Reviewed / Open Access
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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
Author(s)
Sueta D, Yamamoto E*, Tanaka T, Hirata Y, Sakamoto K, Tsujita K, Kojima S, Nishiyama K, Kaikita K, Hokimoto S, Jinnouchi H, Ogawa H.
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Journal Title
IJC Heart & Vasculature
Volume: 8
Pages: 52-4
Peer Reviewed / Open Access
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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
Author(s)
Hokimoto S*, Akasaka T, Tabata N, Arima Y, Tsujita K, Sakamoto K, Kaikita K, Morita K, Kumagae N, Yamamoto E, Oniki K, Nakagawa K, Ogawa H.
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Journal Title
Thromb Res
Volume: 135
Pages: 1081-6
Peer Reviewed / Open Access
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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
Author(s)
Ishihara M*, Fujino M, Ogawa H, Yasuda S, Noguchi T, Nakao K, Ozaki Y, Kimura K, Suwa S, Fujimoto K, Nakama Y, Morita T, Shimizu W, Saito Y, Tsujita K, Nishimura K, Miyamoto Y.
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Journal Title
Circ J
Volume: 79
Pages: 1255-62
Peer Reviewed / Open Access
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[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.
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Journal Title
Int J Cardiol.
Volume: 187
Pages: 411-3
Peer Reviewed / Open Access
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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
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.
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Journal Title
J Cardiol.
Volume: 66
Pages: 353-8
Peer Reviewed / Open Access / Acknowledgement Compliant
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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.
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Journal Title
Am J Physiol Heart Circ Physiol
Volume: 308
Pages: H478-484
Peer Reviewed / Open Access / Acknowledgement Compliant
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