冠状动脉内应用维拉帕米对stemi急诊pci治疗后冠脉灌注心肌灌注和临床预后影响(完整版).docx

冠状动脉内应用维拉帕米对stemi急诊pci治疗后冠脉灌注心肌灌注和临床预后影响（完整版）(文档可以直接使用，也可根据实际需要修改使用,可编辑 欢迎下载）上海交通大学医学院七年制硕士学位论文缩略语表5缩写英文全称中文全称AMIAcute myocardial infarction急性心肌梗死STEMIST segment elevation infarctionST 段抬高性心肌梗死CAGCoronary arteriography冠状动脉造影PCIPercutaneous coronary intervention经皮冠状动脉介入治疗ECGElectrocardiogram心电图TIMIThrombolysis in myocardial infarction心肌梗死溶栓IRAInfarction related artery梗死相关动脉LMLeft main左主干LADLeft anterior descending artery左前降支LCXLeft circumflex coronary artery左回旋支RCARight coronary artery右冠状动脉LVEFLeft ventricular ejection fraction左室射血分数MACEMajor adverse cardial events主要心脏不良事件CTFCCorrected TIMI Frame Count校正的 TIMI 帧数TFGTIMI Flow GradesTIMI 血流分级TMPGTIMI myocardial perfusion gradeTIMI 心肌灌注分级MBGMyocardial blush grade心肌灌注显影分级TMPFCTIMI Myocardial Perfusion Frame CountTIMI 心肌灌注帧数IABPIntra-aortic balloon pump主动脉内球囊反搏CABGCoronary artery bypass graft冠状动脉旁路移植术TVRTarget vessel revascularization靶血管血运重建ACEIAngiotensin-converting enzyme inhibitor血管紧张素转换酶抑制剂上海交通大学医学院七年制硕士学位论文上海交通大学学位论文原创性声明本人郑重声明：所呈交的学位论文，是本人在导师的指导下，独立进行研究工作所取得的成果。除文中已经注明引用的内容外，本论文不包含任何其他个人或集体已经发表或撰写过的作品成果。对本文的研究做出重要贡献的个人和集体，均已在文中以明确方式标明。本人完全意识到本声明的法律结果由本人承担。学位论文作者签名：乔志卿日期：2021 年5 月2 日2上海交通大学医学院七年制硕士学位论文上海交通大学学位论文版权使用授权书本学位论文作者完全了解学校有关保留、使用学位论文的规定，同意学校保留并向国家有关部门或机构送交论文的复印件和电子版，允许论文被查阅和借阅。本人授权上海交通大学可以将本学位论文的全部或部分内容编入有关数据库进行检索，可以采用影印、缩印或扫描等复制手段保存和汇编本学位论文。保密，在本学位论文属于不保密。（请在以上方框内打“”）学位论文作者签名：乔志卿日期：2021 年 5 月 2 日3年解密后适用本授权书。指导教师签名：何奔日期：2021 年 5 月 2 日上海交通大学医学院七年制硕士学位论文冠状动脉内应用维拉帕米对 STEMI 急诊 PCI 治疗后冠脉灌注、心肌灌注和临床预后的影响摘 要目的：探讨急性ST段抬高心肌梗死（ST segment elevation infarction，STEMI）急诊经皮冠脉介入治疗（Percutaneous coronary intervention，PCI）时冠脉内应用维拉帕米对冠脉灌注、心肌灌注及临床预后的影响。并研究急性心梗急诊PCI术后心肌灌注不良(以TMPG评价)的影响因素。另观察本中心提出的一种新的心肌灌注评价指标TIMI心肌灌注帧数(TIMI Myocardial Perfusion Frame Count,TMPFC)的临床影响因素，及其在临床试验中的应用情况。方法：本研究为前瞻性、随机、双盲、对照临床试验，连续入选100例STEMI拟行急诊PCI的患者，随机分为维拉帕米组与对照组，维拉帕米组在支架释放后即刻冠脉内注入维拉帕米200ug/2ml肝素生理盐水，对照组在支架释放后即刻冠脉内注入肝素生理盐水2ml，比较两组PCI术前、术后和冠脉内注药后的冠脉灌注心外膜TIMI血流（TIMI Flow Grades，TFG）和校正的TIMI血流帧数计数(Corrected TIMI Frame Count，CTFC)和心肌灌注水平TIMI心肌灌注分级(TIMI Myocardial Perfusion Grades，TMPG)和心肌灌注显影(TIMI Myocardial Blush Grades，MBG)；并比较6上海交通大学医学院七年制硕士学位论文两组临床结果，包括PCI术后1周心超、住院期间以及随访期间主要心脏不良事件(Major adverse cardiac events,MACE)发生率。所有患者根据PCI术后TMPG分级，分为心肌灌注不良组（TMPG0-2级，n=30）和心肌灌注正常组（TMPG3级，n=61），比较两组基本临床资料和造影结果以及介入结果，并对各因素做logistic回归，总结急性心梗急诊PCI术后心肌灌注不良的影响因素。采用上述同样方法，将所有患者根据TMPFC值分为TMPFC90和TMPFC90两组，观察各临床因素对TMPFC的影响；并将TMPFC应用于上述随机双盲对照试验中，观察维拉帕米干预后TMPFC是否和TMPG产生一样的变化。结果：100例病人中有91例患者最终入选本试验，另9位因造影图像质量未达到试验要求而排除，入选患者中男性76例，女性15例，年龄3884(62.3±11.8)岁，维拉帕米组47人，对照组44人，两组术中应用替罗非班的情况对照组多于维拉帕米组（29.5 %vs10.6 %，p=0.0237），其他临床特征和造影特征两组均无显著差异。冠脉支架释放后即刻冠脉灌注（CTFC、TFG）和心肌灌注水平（TMPG、MBG）两组间均无显著差异；但冠脉内注入维拉帕米后CTFC(p=0.0105)、TFG（p=0.0071）、TMPG（p=0.0315）和 MBG（p=0.0261）均有显著改善；经对替罗非班应用影响因素校正后，CTFC（P=0.0487）仍有显著改善，TFG（P=0.069）、MBG（P=0.0891）有改善的趋势，而TMPG（P=0.123）两组间无显著差7上海交通大学医学院七年制硕士学位论文异。两组PCI术后1周心超结果（LVEF、LVEDD、LVESD）未见显著差异；两组院内MACE事件发生率未达到统计学差异（p=0.6127），1月和3月随访期MACE发生率两组亦未见显著差异（p=0.7060和p=0.894）。心肌灌注不良组（TMPG0-2级）高血压比例更多（80%vs54.1%，p=0.0163），心梗部位以非前壁心梗为多（70%vs29.5%，p=0.002）；造影结果中心肌灌注不良组梗塞相关血管为RCA者更多（63.3%vs18%，p<0.0001），术前CTFC值（97.7 ±±26.4，p=0.0414）和术前MBG0级的比例（93.3%vs75.4%，p=0.0268）也是心肌灌注不良组更高；介入治疗中心肌灌注不良组使用替罗非班的比例更高（33.3 %vs13.1 %，p=0.0228）；单因素回归分析显示高血压、非前壁心梗、发病至球囊开通时间、犯罪血管为RCA、术中需使用替罗非班、术前MBG分级均是PCI术后心肌灌注不良（TMPG分级差）的预测因素，但多因素的Logisti回归分析发现，仅发病至球囊开通时间是PCI术后心肌灌注不良的独立危险因素。和TMPG的影响因素相似，TMPFC的影响因素有非前壁心梗、犯罪血管为RCA、术前CTFC、TFG、MBG分级均是PCI术后TMPFC的影响因素，其中非前壁心梗是PCI术后TMPFC数值偏高的独立危险因素（p=0.0124）。但和TMPG不同的是发病至球囊开通时间并不是TMPFC的影响因素。TMPFC在上述临床试验中的应用，表现出和TMPG、MBG相似的结果，冠脉内注入维拉帕米后TMPFC有显著改善（108.7 ±44.9 vs8上海交通大学医学院七年制硕士学位论文123.3 ±57.8，p=0.0216），而注入对照药物时未见显著差异（134.0 ±66.7vs 141.8 ±74.4，p=0.7215），这和TMPG一致；但给药后维拉帕米组和对照组的TMPFC比较，前者有优于后者的趋势，但无统计学差异（108.7±44.9 vs 134.0 ±66.7，p=0.0899），而TMPG却仍表现出前者显著优于后者的差异。结论：对于急性ST段抬高心肌梗死行急诊PCI治疗的患者，冠状动脉内应用维拉帕米可显著改善冠脉灌注，并有改善心肌灌注的趋势，但对PCI术后心功能和短期临床预后的影响未见显著差异。高血压、非前壁心梗、犯罪血管为RCA、术前CTFC及术前MBG分级、发病至球囊开通时间均是PCI术后TMPG的影响因素，其中发病至球囊开通时间是PCI术后TMPG分级低的独立危险因素，发病至球囊开通时间越长，PCI术后TMPG分级越低。和TMPG的影响因素相似，TMPFC的影响因素有非前壁心梗、犯罪血管为RCA、术前CTFC、TFG和MBG分级，其中非前壁心梗是PCI术后TMPFC数值偏高的独立危险因素；但和TMPG不同的是发病至球囊开通时间并不是TMPFC的影响因素。TMPFC在临床试验的应用中体现了和TMPG类似结果，但其价值有待进一步研究。关键词：心肌梗死，经皮冠状动脉介入，维拉帕米，心肌灌注，冠脉灌注，影响因素9上海交通大学医学院七年制硕士学位论文Effect Of Intracoronary Verapamil OnCoronary Flow，Myocardial Perfusion andClinical Outcome During PercutaneousCoronary Intervention For Acute MyocardialInfarctionABSTRACTObjective To compare the effects of intracoronary verapamil oncoronary flow,myocardial perfusion and clinical outcome with acute STelevation myocardial infaretion (STEMI);and to study influencing factors oflower myocardial perfusion levels as evaluated by TIMI myocardialperfusion grade（TMPG）of STEMI patients undergoing primary PCI.And toobserve influencing factors of TMPFC,a new method of assessing myocardialperfusion and compare it with TMPG in clinical test.Methods A total of 100 consecutive STEMI patients undergoingprimary PCI were randomly assigned to intracoronary verapamil or to10上海交通大学医学院七年制硕士学位论文intracoronary heparinised saline after deploying stent Thrombolysis inMyocardial Infarction (TIMI) flow grade（TFG）,corrected TIMI frame count(CTFC), TIMI myocardial perfusion grade (TMPG)，TIMI Myocardial BlushGrades（ MBG） were assessed pre- and post-PCI and after study drugadministration.Echocardiographywereperformedoneweekafterinfarction, revascularization, angina pectoris,heart failure, readmission) inhospital and 3 months follow-up were compared between two groups.All patients were divided two groups by TMPG after PCI.One groupwas lower myocardial perfusion levels(TMPG 0-2,n=30),the other wasnormal myocardial perfusion levels(TMPG3,n=61).We compare Baselinecharacteristics and Angiographic characteristics between two groups.Andlogistic regression analysis was employed to determine the independentpredictors of low TMPG after PCIAs the same way,all patients were divided two groups by TMPFC.Onewas TMPFC 90,the other was TMPFC 90. We compare Baselinecharacteristics and Angiographic characteristics between two groups.AndTMPFC was applied in clinical test above,in order to observe the differencebetween TMPFC and TMPG in the test.Results Ninety one STEMI patients were enrolled,and nine patients11上海交通大学医学院七年制硕士学位论文were excluded for quality of coronary angiograms after PCI.Among 91patients,76 patients were male and 15 patients were femal aged from 38 to84ys.Except for using Tirofiban(verapamil group10.6 % vs control group29.5%，p=0.0237）, Baseline characteristics and Angiographic characteristics werenot significantly different between two groups.CTFC、TFG、TMPG、MBGafter PCI were were not significantly different between two groups.But afterstudy drug administration, Verapamil group was superior to controll group interms of CTFC(p=0.0105)、TFG（p=0.0071）、TMPG（p=0.0315）and MBG（ p=0.0261） After correcting factor of using Tirofiban, only CTFC（ p=0.0487 ） was still significantly different between two group,TFG（P=0.069）and MBG（P=0.0891）had a same trend,while TMPG（P=0.123）was not significantly different between two groups. LVEF、LVEDD、LVESDafter PCI were not significantly different between two groups.The MACErate in hospital was similar between two groups (p=0.6127).The combinedincidence of MACE during 1-month and 3-month follow-up was notsignificantly lower in the verapamil group compared with control group（p=0.7060 and p=0.894）More hypertensions（80%vs54.1%，p=0.0163）and non-anterior wallinfarction（ 70%vs29.5%， p=0.002） were observed in lower myocardialperfusion levels group.Infarction related arteries were RCA more frequently12上海交通大学医学院七年制硕士学位论文in lower myocardial perfusion levels group than normal myocardial perfusionlevels group（63.3%vs18%，p<0.0001）.CTFC（97.7 ±±26.4，p=0.0414）and rate of MBG 0 grade（93.3%vs75.4%，p=0.0268）before PCIwere higher in lower myocardial perfusion levels group.Rate of usingtirofiban during PCI was higher in lower myocardial perfusion levels groupthan normal myocardial perfusion levels group（33.3 %vs13.1%,p=0.0228）.Univariate logistic regression analysis of the association between clinical andangiographic characteristics, and TMPG shows hypertensions, non-anteriorwall infarction,onset to balloon time, RCA as culprit vessel,using tirofibanand MBG before PCI were correlated with the lower myocardial perfusionafter PCI.Multivariate logistic regression analysis shows only onset toballoon time was the strong predictor of low TMPG after PCI independent ofother prognostic factors.Influencing factors of TMPFC included non-anterior wall infarction ,RCA as culprit vessel and CTFC、TFG、MBG before PCI; and non-anteriorwall infarction was the strong predictor of poor TMPFC after PCIindependent of other prognostic factors（p=0.0124）.But onset to balloon timewas not influencing factor of TMPFC.After intracoronary verapamil, TMPFCwas significantly better than that before administration（108.7 ±44.9 vs 123.3±57.8，p=0.0216）,but it was not better after control drug administration13上海交通大学医学院七年制硕士学位论文（134.0 ±66.7 vs 141.8 ±74.4，p=0.7215）.It was same as TMPG.Wecompared TMPFC after study drug administration between verapamil groupand control group, it was not siginificantly different between two groups（108.7 ±44.9 vs 134.0 ±66.7，p=0.0899）.While TMPG was significantlydifferent between two groups.Conclusion Administration of intracoronary verapamil during primaryPCI significantly improves postprocedural coronary flow as evaluated byCTFC in STEMI patients.And it had a same trend in myocardial perfusion asevaluated by MBG，but it was not statistical significance. Intracoronaryverapamil is not significantly superior left ventricular function and short-timeclinical prognosis compared with the controll in patients with STEMIundergoing primary PCIHypertensions, non-anterior wall infarction ,RCA as culprit vessel, onsetto balloon time,CTFC ,MBG before PCI were influential factors of lowmyocardial perfusion(TMPG0-2).And onset to balloon time was theindependent predictor of low myocardial perfusion.More onset to balloontime,lower TMPG.Non-anterior wall infarction , RCA as culprit vessel and CTFC、TFG、MBG before PCI were influential factors of TMPFC. And non-anterior wallinfarction was the independent predictor of poor TMPFC,while onset to14上海交通大学医学院七年制硕士学位论文balloon time was not influential factors of TMPFC.TMPFC had similarchange with TMPG in our clinical test,but it needs more study toconsummate this new method of assessing myocardial perfusion.KEY WORDSmyocardialinfarction ， percutaneouscoronaryintervention， verapamil， myocardial perfusion, coronary flow,influentialfactor15上海交通大学医学院七年制硕士学位论文前言大规模的临床研究表明，急性心梗早期行急诊PCI能挽救缺血心肌，从而改善近期和远期的临床预后。但约10%30%的患者PCI术后并发无再流或慢血流现象，心外膜血管未能达到TIMI3级血流，即使达到TIMI3级血流，部分病人也未必达到完全的心肌组织水平灌注，结果其再梗、恶性心律失常和心衰的发生率和死亡率明显增加，严重影响AMI患者的预后1。因此治疗STEMI的最终目的是及时、充分的恢复心肌组织水平灌注，从而减轻心肌重构、改善心功能，AMI的理想再灌注治疗应当是在冠脉已再通的基础上，实现心肌水平的完全再灌注。目前评价冠脉灌注的影像学方法有：Gibson等提出的校正的TIMI帧数计数（CTFC）用帧数将冠脉血流灌注量化2，CTFC较TIMI分级在评价血流灌注方面进一步量化，客观性和准确性增强。评价心肌灌注的影像学方法有：由Gibson等1提出的以心肌造影剂进出时间为基础的心肌组织灌注程度的分级方法-TIMI心肌灌注(TIMI Myocardial Perfusion Grading,TMPG)分级；以及 Vant Hof等3提出的另一种以心肌显影密度为基础的MBG分级方法。近年来，改善心肌灌注的干预措施进展较快，针对心肌灌注的临床试验，包括药理性方法，如糖蛋白IIb/IIIa拮抗剂、腺苷、硝普钠、尼可地尔、尼卡地平、链激酶、维拉帕米等；机械性方法，如远端保护装置和抽吸导管等。其中维拉帕米的应用较多，但对维拉帕米是否能真正改善PCI术后冠脉灌注、心肌灌注和临床预后还存在争议，而且既往的临床试验多为回顾性，缺少前瞻性、随机、双盲、对照的临床研究，本研究就是设计一个临床试验来评价维拉帕米对冠脉灌注和心肌灌注的影响。多项研究表明年龄、心功能不全、IRA重建时间、梗死前心绞痛、Q波计数、ST段回落不良等因素是急诊PCI病人术后心功能恢复和主要心血管病事件的影响因素；但这些因素是否均会影响心肌组织微灌注尚不明确。既往的研究多以无/慢血流作为心肌组织灌注不足的评价，而这是以TIMI2级作为灌注不足，这并非心肌水平灌注的评价，本研究以TMPG为评价心肌水平灌注的指标，通过比较心肌水平灌注不良病16上海交通大学医学院七年制硕士学位论文人（TMPG2级）与心肌水平灌注正常病人（TMPG3级）的临床资料进行分析，以探讨导致心肌组织水平灌注不良的危险因素。评价心肌水平灌注的影像学方法主要是Gibson等提出的TMPG和Vant Hof等提出的MBG方法，但这两种心肌水平再灌注评价方法主观性较强无法消除各观察者之间对血流判断上的差异，所以目前尚无一种良好的心肌水平灌注的造影评价指标，本中心提出了一种新的心肌灌注评价系统TMPFC，本中心之前已证实TMPFC对临床预后具有重要的预测价值4，本研究的目的是观察影响TMPFC的临床因素，并将这一新方法应用于临床试验中，与TMPG进行比较。总之，本研究旨在评价冠脉内应用维拉帕米对急性心梗介入治疗后冠脉灌注、心肌灌注和临床预后的影响。同时观察引起心肌灌注不良的可能存在的因素。并将一种新的心肌灌注评价指标（TMPFC）在临床试验中应用。参考文献：1Gibson CM, Cannon CP, Murphy SA, et al.Relationship of TIMI myocardialperfusion grade to mortality after administration of thrombolytic drugs. Circulation2000;101:125130.2Gibson CM, Cannon CP, Daley WL, et al. TIMI frame count: a quantitativemethod of assessing coronary artery flow. Circulation, 1996,93:879888.3vant Hof AWJ, Liem A, Suryapranata H, et al. Angiographic assessment ofmyocardial reperfusion in patients treated with primary angioplasty for acute myocardialinfarction: myocardial blush grade. Circulation,1998, 97: 23022306.4He B, Ding S, Pu J. TIMI myocardial perfusion frame count - a new method forassessing myocardial perfusion. Catheter Cardiovasc Interv 2007; 69:S16.17上海交通大学医学院七年制硕士学位论文第一部分：冠状动脉内应用维拉帕米对STEMI急诊PCI治疗后冠脉灌注、心肌灌注和临床预后的影响前瞻性、随机、双盲、对照临床研究引言大规模临床研究表明，急性心梗（AMI）早期行急诊PCI能挽救缺血心肌，从而改善近期和远期的预后。然而，AMI急诊