ST段抬高心肌梗死直接经皮冠脉介入治疗后心肌灌注不良的预测因素及替罗非班和山莨菪碱的保护作用
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摘要
随着现代冠心病学的不断发展,直接经皮冠状动脉介入治疗(Primary Percutaneous Coronary Intervention,pPCI)已经成为治疗急性ST段抬高型心肌梗死(ST-elevation myocardial infarction,STEMI)的基石,是挽救缺血心肌、缩小梗死面积、改善患者心功能、降低STEMI患者死亡率的最有效的方法。然而,在30%到40%接受再灌注治疗的患者中,梗死相关动脉(Infarct Related Artery,IRA)的开通并没有带来心肌组织微循环灌注的改善,即发生了心肌灌注不良。心肌灌注不良的发生机制目前尚不明确,大量的临床研究和基础实验证实,其与远端血栓栓塞、缺血相关性损伤、缺血-再灌注损伤、机体炎症、应激状态等因素有关。近年来大量的国内外研究表明,心肌灌注不良是梗死延展、心室重塑、心功能障碍、恶性心律失常等并发症的预测指标,发生心肌灌注不良的患者有着更高的院内和远期死亡率。因此,如何实现在开通梗死相关动脉、恢复冠脉前向血流的同时,早期发现、预防和逆转心肌灌注不良,使梗死相关区域心肌组织微循环得到有效的灌注,是目前国内外介入心脏病学领域共同关注的焦点课题。另一方面,直接PCI导致的对比剂肾病是直接影响PCI疗效和并发症的重要因素,其增加了患者死亡率,是介入心脏病学领域遇到的另一难题。据估计,普通人群行冠脉造影检查对比剂肾病的发生率为1%-6%,相比于普通人群,急性心肌梗死患者对比剂肾病的发生率更高,约为19%。
临床研究显示：急性ST段抬高型心肌梗死患者应用血小板GPⅡb/Ⅲa受体拮抗剂可以明显改善心肌梗死患者梗死区心肌灌注和患者的临床预后。冠脉内应用替罗非班将增加梗死相关动脉内替罗非班浓度,有效阻抑血小板聚集,松解血栓,达到最佳的血小板抑制。同时冠脉内应用高剂量替罗非班有利于病变部位及远端微循环血栓、微血栓的溶解,从而改善心肌前向灌注。但目前其最佳应用策略还不清楚,值得进一步探讨。另外我中心前期研究显示：冠脉内应用山莨菪碱可以逆转直接PCI过程中无复流现象,可以有效的改善心肌微循环灌注,挽救濒死心肌。但是无复流一旦发生,药物将很难达到微循环并发挥作用。因此本研究从预防的角度出发,在冠脉无复流发生之前预防性应用替罗非班和山莨菪碱,观察其对无复流的预防及心肌灌注的改善作用,以期为临床实现早期良好的心肌灌注提供参考。
本研究首先回顾性分析患者基本临床资料、冠脉造影及介入结果等相关因素,分析并探讨急性ST段抬高型心肌梗死直接PCI后心肌组织灌注不良和对比剂肾病发生的危险因素。进而通过随机对照的方法应用替罗非班和山莨菪碱对患者进行干预,观察替罗非班和山莨菪碱对STEMI患者直接PCI后心肌灌注的保护作用。
本研究共分为三个部分：
第一部分
ST段抬高型心肌梗死患者直接经皮冠脉介入治疗术后心肌灌注不良的预测因素及其对预后的影响
目的：探讨急性ST段抬高型心肌梗死(ST-elevation myocardial infarction, STEMI)患者直接经皮冠状动脉介入治疗(primary percutaneous coronary intervention, pPCI)后心肌灌注不良的预测因素及其对预后的影响。
方法：回顾性分析2007年1月至2009年1月入住我院行直接PCI治疗的STEMI患者386例(男性322例,女性64例)。根据患者造影灌注积分(angiographic perfusion score, APS)将患者分为三组：完全心肌灌注组(full APS组,积分10-12分),部分心肌灌注组(partial APS组,积分4-9分)和无心肌灌注组(failed APS组,积分0-3分)。比较3组患者基本临床资料,冠脉造影及介入结果,并对各因素进行Logistic回归分析,探讨急性STEMI患者直接PCI后心肌灌注不良的影响因素,同时查阅患者随访资料,观察主要心脏不良事件(major adverse cardiac events, MACE)的发生情况,分析急性ST段抬高型心肌梗死患者直接PCI术后心肌灌注不良对预后的影响。
结果：1三组患者之间的基本临床特点的比较：三组患者在年龄、性别、高血压史、糖尿病史、高脂血症、吸烟史、入院时收缩压、舒张压、心率方面无统计学意义(P>0.05)。在三组患者中,完全心肌灌注组发病至球囊开通时间短于部分心肌灌注组和无心肌灌注组(6.5±2.9h vs.7.4±2.8h vs.8.1±2.6h,P=0.014),差异有统计学意义；完全心肌灌注组梗死前心绞痛的发生率明显高于部分心肌灌注组和无心肌灌注组(42.1％vs.28.4％vs.25.0％,P=0.006),但部分心肌灌注组和无心肌灌注组之间无统计学差异；完全心肌灌注组静脉应用替罗非班的比例较高(64.3％VS.53.2％vs.42.9％,P=0.037)；完全心肌灌注组患者入院时Killip分级II级及以上比例明显低于部分心肌灌注组和无心肌灌注组(23.6％vs.39.9％vs.46.4％,P=0.003),但部分心肌灌注组和无心肌灌注组之间没有差别；无心肌灌注组患者入院时血糖明显高于部分心肌灌注组和完全心肌灌注组(9.2±3.6mmol/L vs.8.6±2.8mmol/L vs.7.7±3.2mmol/L,P=0.001),无心肌灌注组CK(2851±1386U/L vs.2673±1452U/L vs.2436±1328U/L, p=-0.026)及CK-MB(259±129U/L vs.236±151U/L vs.218±142U/L, P=0.018)峰值水平也较部分心肌灌注组和完全心肌灌注组明显升高。
2三组患者之间冠脉造影及PCI结果的比较：在冠脉造影和PCI各相关因素中,病变血管支数、侧支循环在三组之间无统计学意义(P>0.05)。无心肌灌注组患者靶血管为LAD的比例明显高于部分心肌灌注组和完全心肌灌注组(71.4％vs.62.8％vs.58.6％,P=0.036),但完全心肌灌注组和部分心肌灌注组之间没有差别。无心肌灌注组高血栓负荷所占比例明显高于部分心肌灌注组和完全心肌灌注组(64.3％vs.49.4％vs.33-3％, P=0.002)。
3Logistic回归分析显示：梗死前心绞痛,入院时血糖水平,发病至球囊开通时间,血栓负荷、静脉应用替罗非班是心肌灌注水平的独立预测因素。随访结果显示：心肌灌注不良组患者MACE发生率较高(26.9%vs.9.0%,P=0.016),预后不佳。
结论：1.梗死前心绞痛,入院时血糖水平,发病至球囊开通时间,血栓负荷及静脉应用替罗非班是急性STEMI患者直接PCI术后心肌灌注不良的独立预测因素。
2.STEMI患者直接PCI术后心肌灌注不良患者MACE发生率高,预后不佳。
第二部分
对比剂用量与估测的肾小球率过滤比值对行直接PCI治疗的急性ST段抬高心肌梗死患者对比剂肾病的预测价值
目的：本研究旨在评价对比剂用量与估测的肾小球率过滤比值(CMV/eGFR)对行直接经皮冠状动脉介入治疗(PCI)的ST段抬高心肌梗死(STEMI)患者对比剂肾病(CIN)的预测价值。
方法：回顾性分析2008年1月至2009年1月入住我院行直接PCI治疗的STEMI患者114例(男性92例,女性22例),研究CIN发生的相关临床因素。CIN的危险因素包括年龄,性别,体重指数,左室射血分数,血红蛋白,对比剂用量,基础血肌酐水平,病变血管数,支架的数量。应用逐步回归分析评价上述危险因素对CIN的预测价值。
结果：1.对比剂肾病的发生率为18.4%(21／114),对比剂肾病组(n=21)与非对比剂肾病组(n=93)在年龄、性别、体重指数、左室射血分数、血红蛋白以及高血压等方面的基线资料无明显差异。
2.对比肾病组eGFR [(72.0±12.5) ml·min-1·1.73m-2vs.(82.0±16.5) ml·min-1·1.73m2,P=0.010]明显低于非对比剂肾病组,基础的血肌酐水平[(1.07±0.12) mg/dl vs.(0.97±0.19) mg/dl, P=0.014]明显高于非对比剂肾病组。此外,对比剂肾病组对比剂用量[(253±75) ml vs.(211±71) ml, P=0.017]明显多于非对比剂肾病组,对比剂肾病组CMV/eGFR比值较高(3.64±1.26vs.2.70±1.11,P=0.001)。
3.逐步回归分析显示CMV/eGFR是CIN的一个重要的独立预测因素(P=0.001)。在截断点为3.1时,CMV/eGFR对CIN的预测价值敏感性和特异性分别为71%和70%。
结论：1. CMV/eGFR是STEMI接受直接PCI过程中CIN发生的重要预测因素。
2.在CMV/eGFR截断点为3.1时,其对CIN的发生具有良好的预测价值。
第三部分
优化的替罗非班应用方法对急性ST段抬高型心肌梗死患者直接经皮冠脉介入治疗术后心肌组织灌注的改善作用
目的：探讨在应用阿司匹林,氯比格雷,肝素的基础上,优化的替罗非班临床应用策略对急性ST段抬高型心肌梗死(ST elevation myocardial infarction, STEMI)患者直接经皮冠状动脉介入治疗(primary percutaneous coronary intervention, pPCI)后心肌灌注的作用。
方法：从2009年10月到2010年10月,入住我科行直接PCI的195名STEMI患者,随机分到研究组(n=99)和对照组(n=96)。所有的患者在急诊室确诊为急性ST段抬高型心肌梗死后,立即给予阿司匹林,氯比格雷,肝素及替罗非班(上游应用,10μg/kg3分钟内缓慢静推,继而以0.15μg·kg-1·min-1的速率维持静点)等药物治疗。研究组的患者在开通冠脉前向血流即刻冠脉内再次给予负荷量替罗非班(冠脉内应用,15μg/kg3分钟内缓慢推注)。对照组的患者以同样的方法冠脉内给予等剂量的生理盐水做对照。评价PCI术后心肌梗死溶栓治疗(thrombolysis in myocardial infarction, TIMI)分级、校正的TIMI血流计帧数(Corrected TIMI Frame Count, CTFC)、心肌梗死溶栓治疗心肌灌注分级(TIMI myocardial perfusion grade, TMPG)和主要心脏不良事件(major adverse cardiac events, MACE)的发生情况。所有患者PCI术后给予标准的药物治疗。
结果：1.两组患者基本临床资料的比较：两组患者在年龄、性别、高血压史,糖尿病史、高脂血症、吸烟史、Killip分级、症状发生至球囊开通时间、首次应用替罗非班至球囊开通时间、入院时收缩压,舒张压、心率方面没有统计学差异,但研究组CK峰值(2157.3±1250.1U/L vs.2573.9±1423.6U/L, P=0.031)及CK-MB峰值(197.±120.1U/L vs.243.9±143.6U/L, P=0.024)明显低于对照组。
2.两组患者造影及PCI结果的比较：两组患者在梗死相关血管的分布,多支血管病变的发生情况,术前靶血管的心肌梗死溶栓治疗(Thrombolysis in Myocardial Infarction, TIMI)分级方面无统计学差异。两组患者之间支架的长度和直径也没有统计学意义。尽管两组患者血栓负荷和血栓抽吸方面没有统计学意义,但是研究组患者发生血栓栓塞的情况明显低于对照组(5.1%vs.15.6%,P=0.015)。研究组患者达到TIMI3级(91.9%vs.80.2%,P=0.018)及心肌梗死溶栓治疗心肌灌注分级(TIMI myocardial perfusion grade, TMPG)3级(72.7%vs.52.1%,P=0.003)的比例明显高于对照组。研究组中有91例(91.9%)的患者达到了TIMI3级,而对照组只有77例(80.2%)患者达到TIMI3级水平。研究组中有72例(72.7%)的患者达到了TMPG3级,而对照组只有50例(52.1%)患者达到TMPG3级水平。研究组患者校正的TIMI血流计帧数(Corrected TIMI Frame Count, CTFC)明显低于对照组(19±8vs.22±9,P=0.015)。多元Logistic回归分析显示：血栓负荷(odds ratio [OR],2.54;95%CI,1.18to5.49; P=0.017), PCI术前TIMI血流(OR,0.73;95%CI,0.56to0.96; P=0.022)和冠脉内应用替罗非班(OR,0.31;95%CI,0.15to0.65; P=0.002)是TMPG的独立预测因素。
3.30天的随访结果显示：研究组主要心脏不良事件(major adverse cardiac events, MACE)的发生明显低于对照组(P=0.030),左室射血分数明显高于对照组(56.3±10.0%vs.51.7±7.4%,P=0.016)。两组患者出血并发症相似(P=0.621)。
结论：1.在应用阿司匹林、氯比格雷和肝素的基础上,上游加冠脉内应用高剂量替罗非班可以明显改善急性ST段抬高型心肌梗死患者直接PCI术后心肌组织灌注。
2.上游加冠脉内应用高剂量替罗非班可以改善患者30天的心功能,减低MACE发生。
3.上游加冠脉内应用高剂量替罗非班不增加出血风险。
第四部分
预防性冠脉内应用山莨菪碱对急性ST段抬高型心肌梗死患者直接经皮冠脉介入治疗后心肌灌注的改善作用
目的：临床研究显示冠脉内应用山莨菪碱可以逆转急性ST段抬高型心肌梗死(ST elevation myocardial infarction, STEMI)患者直接经皮冠状动脉介入治疗(primary percutaneous coronary intervention, pPCI)后无复流,改善心肌灌注,从而挽救濒死心肌。本研究的目的是评价预防性冠脉内应用山莨菪碱对STEMI患者直接PCI后心肌灌注的作用。
方法：从2011年1月到2012年1月,于我院行直接PCI的186名急性心肌梗死患者入选本研究,入选患者被随机分到山莨菪碱组(山莨菪碱组,ANI, n=95)或对照组(对照组,CON, n=91)。所有的患者在急诊室确诊为急性ST段抬高型心肌梗死后,立即给予阿司匹林,氯比格雷,肝素及替罗非班(10μg/kg3分钟内缓慢静推,继而以0.15μg·kg-1·min-1的速率维持静点)等药物治疗。山莨菪碱组患者在球囊扩张前冠脉内给予山莨菪碱(2mg,10ml),然后立即行PCI治疗,对照组患者则以同样的方法在冠脉内给予生理盐水。评价PCI术后心肌梗死溶栓治疗(thrombolysis in myocardial infarction, TIMI)分级、校正的TIMI血流计帧数(Corrected TIMI Frame Count, CTFC),心肌梗死溶栓治疗心肌灌注分级(TIMImyocardial perfusion grade, TMPG)和主要心脏不良事件(major adverse cardiac events, MACE)的发生情况。所有患者PCI术后给予标准的药物治疗。
结果：1.两组患者基本临床资料的比较：两组患者在年龄、性别、高血压史,糖尿病史、高脂血症、吸烟史、血管再通时间、入院时收缩压,舒张压、心率方面没有统计学差异,但山莨菪碱组CK峰值(2125.4±1510.1U/L vs.2566.8±1441.5U/L, P=0.042)及CK-MB峰值(162.7±101.5U/L vs.201.4±137.9U/L,P=0.030)水平明显低于对照组。
2.两组患者在梗死相关血管分布,术前血栓负荷,术前TIMI血流,支架的长度和直径方面没有统计学差异。山莨菪碱组患者PCI术后TIMI、 CTFC和TMPG明显好于对照组(P值分别为0.040、0.016和0.005)。山莨菪碱组中有87例(91.6%)的患者达到了TIMI3级,而对照组只有74例(81.3%)患者达到TIMI3级水平。山莨菪碱组中有71例(74.7%)的患者达到了TMPG3级,而对照组只有50例(54.9%)患者达到TMPG3级水平。山莨菪碱组患者CTFC的水平明显低于对照组(20±8vs.23±8,P=0.016)。虽然应用山莨菪碱后患者心率有所增加,但冠脉应用山莨菪碱期间和山莨菪碱后没有心律失常发生。多因素回归分析显示：冠脉内应用山莨菪碱(OR,0.34；95％CI,0.15to0.74；p=0.007),PCI术前TIMI血流(OR,0.67；95％CI,0.44to0.85；p=0.012),血栓负荷(OR,2.60；95％CI,1.11to6.09；P=0.029)是TMPG的独立预测因素。
3.30天随访结果。冠脉内预防性应用山莨菪碱显示了良好的安全性,山莨菪碱组患者30天的MACE发生明显低于对照组(P=0.036)。左室射血分数明显高于对照组(P=0.011)。
结论：1冠脉内预防性应用山莨菪碱可以改善急性ST段抬高型心肌梗死患者直接PCI后的心肌灌注水平.
2冠脉内预防性应用山莨菪碱改善患者心室功能,减低MACE发生。
3冠脉内应用山莨菪碱安全性良好。
With the development of modern medicine, early reperfusion therapy, especially primary percutaneous coronary intervention (pPCI) has become the cornerstone treatment for patients with acute ST-segment elevation myocardial infarction (STEMI), which is the most effective way to save the ischemic myocardium, reduce infarct size, prevent left ventricular remodeling, improve cardiac function, and to reduce mortality. However, in30%to40%of patients, the re-opening of the infarct-related artery did not lead to the improvement of myocardial tissue perfusion, named "poor myocardial perfusion". The mechanism of poor myocardial perfusion is not clear, a large number of clinical studies and animal experiments showed that distal embolization, thrombosis, ischemic related injury, ischemia-reperfusion injury, inflammatory are the causes of poor myocardial perfusion. Recently, a large number of clinical studies have shown that the poor myocardial perfusion is a predictor of myocardial perfusion dysfunction, infarct area extension, ventricular remodeling, heart dysfunction, malignant ventricular arrhythmias, serious complications and long-term mortality. Therefore, early detection, prevention and treatment of poor myocardial perfusion are the common focus in interventional cardiology. Contrast-induced nephropathy (CIN) is another common problem in interventional cardiology. The overall incidence of CIN in the general population has been estimated to lie between1%-6%. Compared to the general population, the incidence in patients with STEMI is considerably higher, which is about19%.
Results from several large clinical trials suggested that platelet GP Ⅱb/Ⅲa inhibitors could significantly improve reperfusion of infarct area and clinical outcomes of patients with STEMI. Meanwhile, intracoronary administration of platelet GP Ⅱb/Ⅲa inhibitors will increase the drug's concentration in the infarct related artery, which may inhibits platelet activation and achieves optimal platelet inhibition. Intracoronary administration of platelet GP Ⅱb/Ⅲa inhibitors may also facilitate the diffusion of them to platelets inside flow-limiting thrombi, resulting in an improved dissolution of thrombi and microemboli at the culprit lesion and in the distal microcirculation, which may be related with improved myocardial perfusion. However, the optimal administration strategy for these agents in this setting remains unclear. In addition, our previous study showed intracoronary anisodamine administered has been proved to be effective in reversing no reflow during primary PCI and improving microvascular perfusion and myocardial salvage. However, once no reflow occurs, it is difficult for pharmacologic agents to reach the microvasculature and take effect. Therefore, this study was done from a prevention perspective to observe the the preventive effect of tirofiban and anisodamine for STEMI patients undergoing primary PCI, and provide a reference for the early optimal myocardial perfusion in clinical practice.
This study was designed to analysis the risk factors of poor myocardial tissue perfusion and CIN in patients with STEMI by retrospectively analysis of clinical data, coronary angiography and intervention results. The protective effect of tirofiban and anisodamine for patients with STEMI were investigated by randomized controlled study.
The detailed methods and results of our study are as follows:
Part Ⅰ
The predictive factors and prognosis effects of poor myocardial perfusion after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction
Objectives:To explore the predictive factors and prognosis effects of poor myocardial perfusion after primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).
Methods:We retrospectively analyzed a total of386consecutive patients (322male and64female) with STEMI who underwent primary PCI within12h of symptom onset from January2007to January2009in this study. Patients were divided into three groups according to angiographic perfusion score:full perfusion group (APS total score10-12, n=140), partial perfusion group (APS total score4-9, n=218) and failed perfusion group (APS total score0-3, n=28). The basic clinical characteristics, angiographic findings and intervention results between these three groups were compared, and multivariate logistic regression analysis was performed to analyze the predictive factors of poor myocardial perfusion after primary PCI in patients with STEMI. Besides, the major adverse cardiac events (MACE) of the patients in the three groups, including cardiac deaths, recurrent nonfatal myocardial infarction, and target vessel revascularization, were observed in hospital and follow-up period. The prognosis effects of poor myocardial perfusion after primary PCI in STEMI were analyzed.
Results:1. There were no significant differences between the three groups with respect to age, gender, hypertension, hypercholesterolemia, diabetes, smoking, systolic blood pressure, diastolic blood pressure, heart rates on admission (all P value>0.05). Among the clinical factors, the time from symptom onset to balloon was shorter in full perfusion group(6.5±2.9h vs.7.4±2.8h vs.8.1±2.6, P=0.014) than that in partial perfusion group and failed perfusion group. The incidence of pre-infarction angina (42.1%vs.28.4%vs.25.0%, P=0.006) was higher in full perfusion group than that in partial perfusion group and failed perfusion group, but there was no significant differences between the partial perfusion group and failed perfusion group. The ratio of tirofiban administration (64.3%vs.53.2%vs.42.9%, P=0.037) was higher in full perfusion group than that in partial perfusion group and failed perfusion group. The ratio of patients with Killip grade≥Ⅱ was higher in failed perfusion group and partial perfusion group than that in full perfusion group (23.6%vs.39.9%vs.46.4%, P=0.003), but there was no significant differences between the partial perfusion group and failed perfusion group. The level of serum glucose on admission was higher in failed perfusion group than that in partial perfusion group and full perfusion group (9.2±3.6mmol/L vs.8.6±2.8mmol/L vs.7.7±3.2mmol/L, P=0.001), the peak CK (2851±1386U/L vs.2673±1452U/L vs.2436±1328U/L, P=0.026) and CK-MB (259±129U/L vs.236±151U/L vs.218±142U/L, P=0.018) level were also higher in failed perfusion group.
2. Angiographic studies demonstrated no significant differences in the incidence of collateral circulation and multivessel disease between the three groups. The ratio of LAD related infarction was much higher in failed perfusion group (71.4%vs.62.8%vs.58.6%, P=0.036) than that in partial perfusion group and full perfusion group. The proportion of visible thrombus was higher in failed perfusion group than that in partial perfusion group and full perfusion group (64.3%vs.49.4%vs.33.3%, P=0.002).
3. Multivariate logistic regression analysis showed that pre-infarction angina, the level of serum glucose on admission, the time from symptom onset to balloon, visible thrombus, tirofiban administration were the independent predictive factors of myocardial perfusion after primary PCI in patients with STEMI. Compared to full myocardial perfusion group, the incidence of MACE was higher in partial perfusion groups and the failed perfusion group.
Conclusions:
1. Pre-infarction angina, hyperglycemia on admission, the time from symptom onset to balloon, visible thrombus, tirofiban administration were the independent predicting factors of APS after primary PCI in patients with STEMI.
2. The incidence of MACE was higher in the poor perfusion group than that in normal perfusion groups.
Part II
Prediction of contrast-induced nephropathy in ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention:role of the ratio of contrast medium volume to estimated glomerular filtration rate
Objective:This study was designed to assess the predictive role of the ratio of contrast medium volume to estimated glomerular filtration rate (CMV/eGFR) in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) who developed contrast-induced nephropathy (CIN).
Methods:We retrospectively investigated clinical factors associated with the development of CIN in114STEMI patients who had undergone primary PCI. The risk factors for CIN included age, gender, body mass index (BMI), left ventricular ejection fraction (LVEF), hemoglobin (Hb), volume of contrast medium, basic levels of serum creatinine (Scr), the number of treated vessels and the number of stents used. We conducted a stepwise regression analysis to evaluate the predictive role of these risk factors in the incidence of CIN.
Results:1. The incidence of CIN was18.4%(21/114). There were no significant differences in age, gender, BMI, LVEF, Hb and incidence of hypertension in patients between the CIN (n=21) and the non-CIN (n=93) groups.
2. The eGFR was significantly lower ((72.0±12.5) ml·min-1·1.73m-2vs.(82.0±16.5) ml·min-1·1.7m-2, P=0.010), and the basic serum creatinine level ((1.07±0.12) mg/dl vs.(0.97±0.19) mg/dl P=0.014) was significantly higher in the CIN group. In addition, the volume of contrast medium was significantly larger ((253±75) ml vs.(211±71) ml, P=0.017) and the CMV/eGFR ratio was significantly greater (3.64±1.26vs.2.70±1.11, P=0.001) in the CIN group.
3. Stepwise regression analysis showed that the CMV/eGFR ratio was a significant independent predictor for the development of CIN (P=0.001). At a cut-off point of>3.1, the CMV/eGFR ratio exhibited71%sensitivity and70%specificity for detecting CIN.
Conclusions:
1. The CMV/eGFR ratio could be a valuable predictor of CIN for STEMI patients after primary PCI.
2. The CMV/eGFR ratio was an optimal predictor for the incidence of CIN at a cut-off point of>3.1,
Part III
New strategy of tirofiban administration improve myocardial perfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention
Objectives:To evaluate the effect of a new regimen of high bolus tirofiban administration on the myocardial perfusion on top of aspirin, clopidogrel and heparin.
Methods:From October2009to October2010, A total of195consecutive patients with STEMI eligible for primary percutaneous coronary intervention (pPCI) were randomly assigned to either study group (n=99) or control group (n=96). All patients in the two groups were pretreated with aspirin, clopidogrel, heparin, and intravenous tirofiban (upstream,10μg/kg over3min as a bolus, then followed by maintenance intravenous tirofiban infusion at0.15μg·kg-1·min-1for24h) in the emergency room immediately after diagnosis was confirmed. Patients in the study group recieved additional bolus tirofiban (intracoronary,15μg/kg over3min) injection immediately after first restoration of antegrade flow, while patients in the control group received intracoronary administration of0.9%sodium chloride of the same volume as study group in the same way. Angiographic analysis included initial and final TIMI grade flow, corrected TIMI frame count, and TIMI myocardial perfusion grade of the culprit vessel. Distal embolism in the targeted vessels was evaluated following PCI. These parameters above were assessed by two independent cardiologists who were blinded to the procedures. All patients in the two groups received standard theraphy after PCI.
Results:1. The two groups were well matched with respect to age, gender, history, high risk factors, Killip classification, time from symptom onset to balloon, initial tirofiban bolus to balloon time, blood pressure, heart rate, but peak CK (2157.3±1250.1U/L vs.2573.9±1423.6U/L, P=0.031) and CK-MB (197±120.1U/L vs.243.9±143.6U/L,P=0.024) levels were lower in anisodamine group
2. Angiographic studies demonstrated no significant differences in the distribution of infarct-related vessel, incidence of multivessel disease, pre-interventional TIMI flow grades between the two groups. The length and diameter of stent were also similar between the two groups. Although the visible thrombus and thrombus aspiration were similar between the two groups, the incidence of distal embolism was lower in the study group (5.1%vs.15.6%, P=0.015). Patients in the study group had better Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count(CTFC), and TIMI myocardial perfusion grade (TMPG) than the subjects in the control group (P=0.018, P=0.015and P=0.003, respectively). TIMI flow grade3was observed in91patients (91.9%) of the study group and in77(80.2%) of the control subjects (P=0.018). CTFC was significantly lower in the ANI group (19±8vs.22±9, P=0.015). TMPG3was seen in72patients (72.7%) of study group and in50(52.1%) of the control subjects (P=0.003). The results of multiple logistic regression showed that visible thrombus (odds ratio [OR],2.54;95%CI,1.18to5.49; P=0.017), pre-PCI TIMI flow (OR,0.73;95%CI,0.56to0.96; P=0.022) and intracoronary tirofiban (OR,0.31;95%CI,0.15to0.65; P=0.002) were all independent predictors of TMPG.
3. Left ventricular ejection fraction was higher in the study group at30 days (56.3±10.0%vs.51.7±7.4%, P=0.016), while the incidence of major adverse cardiac events was lower (P=0.030). The bleeding complications were similar between the two groups during hospitalization and30days follow-up.
Conclusions:1. Upstream plus intracoronary administration of high bolus tirofiban on top of aspirin, clopidogrel and heparin improves myocardial perfusion for STEMI patients undergoing primary percutaneous coronary intervention.
2. Upstream plus intracoronary administration of high bolus tirofiban improve left ventricular ejection fraction, reduces the incidence of major adverse cardiac events.
3. Upstream plus intracoronary administration of high bolus tirofiban doesn't increase major bleeding.
Part IV
Preventively intracoronary administration of anisodamine improves myocardial perfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention
Objectives:Intracoronary anisodamine have been administered for reversing no reflow during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) and have been shown to improve microvascular perfusion and myocardial salvage. This study was designed to evaluate preventively administration of intracoronary anisodamine on myocardial perfusion in terms of slow/no reflow during primary PCI.
Methods:From January2011to January2012, a total of186patients underwent primary PCI within12hours from the onset of STEMI were enrolled. Eligible patients were randomly assigned to receive anisodamine (anisodamine group, ANI, n=95) or placebo (control group, CON, n=91). All patients in the two groups were pretreated with aspirin, clopidogrel, heparin, and intravenous tirofiban (10μg/kg over3min as a bolus, then followed by maintenance intravenous tirofiban infusion at0.15μg·kg-1·min-1for24h) in the emergency room immediately after diagnosis was confirmed. Intracoronary anisodamine (2mg,10ml) was administered immediately prior to balloon inflation and at short intervals during the procedure thereafter, while patients in CON group received intracoronary administration of0.9%sodium chloride with the same volume as ANI group (10ml) in the same way. Angiographic analysis included initial and final TIMI grade flow, corrected TIMI frame count, and TIMI myocardial perfusion grade of the culprit vessel. These parameters above were assessed by two independent cardiologists who were blinded to the procedures. All patients in the two groups received standard theraphy after PCI.
Results:1. The two groups had similar clinical characteristics. No significant differences were demonstrated between the two groups with regards to age, gender, history, high risk factors, Killip classification, time from symptom onset to PCI, left ventricular ejection fraction (LVEF), blood pressure, heart rate, but peak CK (2125.4±1510.1U/L vs.2566.8±1441.5U/L, P=0.042) and CK-MB (162.7±101.5U/L vs.201.4±137.9U/L,P=0.030) levels were lower in anisodamine group.
2. There were no significant differences between the two groups with respect to the distribution of IRA, the length and the diameter of stents. Both groups had similar pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow grade and visible thrombus. The patients treated with intracoronary anisodamine had better post-PCI TIMI flow grade, corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) than those in the control group(P=0.040, P=0.016, and P=0.005, respectively). TIMI flow grade3was observed in87of the patients (91.6%) who received intracoronary anisodamine and in74of the control subjects (81.3%) who received placebo (P=0.040). CTFC was significantly lower in the ANI group (20±8vs.23±8, P=0.016). TMPG3was seen in71of the patients (74.7%) who received intracoronary anisodamine and in50of the control subjects (54.9%) who received placebo (P=0.005). Although patients' heart rates increased after administration of anisodamine, no tachyarrhythmia happened during and after anisodamine administration. Multiple logistic regression analysis found that intracoronary anisodamine (OR,0.34;95%CI,0.15to0.74; P=0.007), initial TIMI flow (OR,0.67;95%CI,0.44to0.85; P=0.012), visible thrombus (OR,2.60;95%CI,1.11to6.09; P=0.029) were independent predictors of TMPG。
3. Compared with control group, intracoronary anisodamine showed a good safety and the incidence of MACE was significantly lower in the ANI group during30days follow-up (P=0.036). Left ventricular ejection fraction was higher in the study group during30days follow-up (P=0.011).
Conclusions:1Intracoronary administration of anisodamine immediately prior to balloon inflation improves postprocedural myocardial perfusion for STEMI patients undergoing primary percutaneous coronary intervention.
2Intracoronary administration of anisodamine improves left ventricular function and reduces MACE at30days.
3Intracoronary administration of anisodamine is safe, with few side effects.
临床研究显示：急性ST段抬高型心肌梗死患者应用血小板GPⅡb/Ⅲa受体拮抗剂可以明显改善心肌梗死患者梗死区心肌灌注和患者的临床预后。冠脉内应用替罗非班将增加梗死相关动脉内替罗非班浓度,有效阻抑血小板聚集,松解血栓,达到最佳的血小板抑制。同时冠脉内应用高剂量替罗非班有利于病变部位及远端微循环血栓、微血栓的溶解,从而改善心肌前向灌注。但目前其最佳应用策略还不清楚,值得进一步探讨。另外我中心前期研究显示：冠脉内应用山莨菪碱可以逆转直接PCI过程中无复流现象,可以有效的改善心肌微循环灌注,挽救濒死心肌。但是无复流一旦发生,药物将很难达到微循环并发挥作用。因此本研究从预防的角度出发,在冠脉无复流发生之前预防性应用替罗非班和山莨菪碱,观察其对无复流的预防及心肌灌注的改善作用,以期为临床实现早期良好的心肌灌注提供参考。
本研究首先回顾性分析患者基本临床资料、冠脉造影及介入结果等相关因素,分析并探讨急性ST段抬高型心肌梗死直接PCI后心肌组织灌注不良和对比剂肾病发生的危险因素。进而通过随机对照的方法应用替罗非班和山莨菪碱对患者进行干预,观察替罗非班和山莨菪碱对STEMI患者直接PCI后心肌灌注的保护作用。
本研究共分为三个部分：
第一部分
ST段抬高型心肌梗死患者直接经皮冠脉介入治疗术后心肌灌注不良的预测因素及其对预后的影响
目的：探讨急性ST段抬高型心肌梗死(ST-elevation myocardial infarction, STEMI)患者直接经皮冠状动脉介入治疗(primary percutaneous coronary intervention, pPCI)后心肌灌注不良的预测因素及其对预后的影响。
方法：回顾性分析2007年1月至2009年1月入住我院行直接PCI治疗的STEMI患者386例(男性322例,女性64例)。根据患者造影灌注积分(angiographic perfusion score, APS)将患者分为三组：完全心肌灌注组(full APS组,积分10-12分),部分心肌灌注组(partial APS组,积分4-9分)和无心肌灌注组(failed APS组,积分0-3分)。比较3组患者基本临床资料,冠脉造影及介入结果,并对各因素进行Logistic回归分析,探讨急性STEMI患者直接PCI后心肌灌注不良的影响因素,同时查阅患者随访资料,观察主要心脏不良事件(major adverse cardiac events, MACE)的发生情况,分析急性ST段抬高型心肌梗死患者直接PCI术后心肌灌注不良对预后的影响。
结果：1三组患者之间的基本临床特点的比较：三组患者在年龄、性别、高血压史、糖尿病史、高脂血症、吸烟史、入院时收缩压、舒张压、心率方面无统计学意义(P>0.05)。在三组患者中,完全心肌灌注组发病至球囊开通时间短于部分心肌灌注组和无心肌灌注组(6.5±2.9h vs.7.4±2.8h vs.8.1±2.6h,P=0.014),差异有统计学意义；完全心肌灌注组梗死前心绞痛的发生率明显高于部分心肌灌注组和无心肌灌注组(42.1％vs.28.4％vs.25.0％,P=0.006),但部分心肌灌注组和无心肌灌注组之间无统计学差异；完全心肌灌注组静脉应用替罗非班的比例较高(64.3％VS.53.2％vs.42.9％,P=0.037)；完全心肌灌注组患者入院时Killip分级II级及以上比例明显低于部分心肌灌注组和无心肌灌注组(23.6％vs.39.9％vs.46.4％,P=0.003),但部分心肌灌注组和无心肌灌注组之间没有差别；无心肌灌注组患者入院时血糖明显高于部分心肌灌注组和完全心肌灌注组(9.2±3.6mmol/L vs.8.6±2.8mmol/L vs.7.7±3.2mmol/L,P=0.001),无心肌灌注组CK(2851±1386U/L vs.2673±1452U/L vs.2436±1328U/L, p=-0.026)及CK-MB(259±129U/L vs.236±151U/L vs.218±142U/L, P=0.018)峰值水平也较部分心肌灌注组和完全心肌灌注组明显升高。
2三组患者之间冠脉造影及PCI结果的比较：在冠脉造影和PCI各相关因素中,病变血管支数、侧支循环在三组之间无统计学意义(P>0.05)。无心肌灌注组患者靶血管为LAD的比例明显高于部分心肌灌注组和完全心肌灌注组(71.4％vs.62.8％vs.58.6％,P=0.036),但完全心肌灌注组和部分心肌灌注组之间没有差别。无心肌灌注组高血栓负荷所占比例明显高于部分心肌灌注组和完全心肌灌注组(64.3％vs.49.4％vs.33-3％, P=0.002)。
3Logistic回归分析显示：梗死前心绞痛,入院时血糖水平,发病至球囊开通时间,血栓负荷、静脉应用替罗非班是心肌灌注水平的独立预测因素。随访结果显示：心肌灌注不良组患者MACE发生率较高(26.9%vs.9.0%,P=0.016),预后不佳。
结论：1.梗死前心绞痛,入院时血糖水平,发病至球囊开通时间,血栓负荷及静脉应用替罗非班是急性STEMI患者直接PCI术后心肌灌注不良的独立预测因素。
2.STEMI患者直接PCI术后心肌灌注不良患者MACE发生率高,预后不佳。
第二部分
对比剂用量与估测的肾小球率过滤比值对行直接PCI治疗的急性ST段抬高心肌梗死患者对比剂肾病的预测价值
目的：本研究旨在评价对比剂用量与估测的肾小球率过滤比值(CMV/eGFR)对行直接经皮冠状动脉介入治疗(PCI)的ST段抬高心肌梗死(STEMI)患者对比剂肾病(CIN)的预测价值。
方法：回顾性分析2008年1月至2009年1月入住我院行直接PCI治疗的STEMI患者114例(男性92例,女性22例),研究CIN发生的相关临床因素。CIN的危险因素包括年龄,性别,体重指数,左室射血分数,血红蛋白,对比剂用量,基础血肌酐水平,病变血管数,支架的数量。应用逐步回归分析评价上述危险因素对CIN的预测价值。
结果：1.对比剂肾病的发生率为18.4%(21／114),对比剂肾病组(n=21)与非对比剂肾病组(n=93)在年龄、性别、体重指数、左室射血分数、血红蛋白以及高血压等方面的基线资料无明显差异。
2.对比肾病组eGFR [(72.0±12.5) ml·min-1·1.73m-2vs.(82.0±16.5) ml·min-1·1.73m2,P=0.010]明显低于非对比剂肾病组,基础的血肌酐水平[(1.07±0.12) mg/dl vs.(0.97±0.19) mg/dl, P=0.014]明显高于非对比剂肾病组。此外,对比剂肾病组对比剂用量[(253±75) ml vs.(211±71) ml, P=0.017]明显多于非对比剂肾病组,对比剂肾病组CMV/eGFR比值较高(3.64±1.26vs.2.70±1.11,P=0.001)。
3.逐步回归分析显示CMV/eGFR是CIN的一个重要的独立预测因素(P=0.001)。在截断点为3.1时,CMV/eGFR对CIN的预测价值敏感性和特异性分别为71%和70%。
结论：1. CMV/eGFR是STEMI接受直接PCI过程中CIN发生的重要预测因素。
2.在CMV/eGFR截断点为3.1时,其对CIN的发生具有良好的预测价值。
第三部分
优化的替罗非班应用方法对急性ST段抬高型心肌梗死患者直接经皮冠脉介入治疗术后心肌组织灌注的改善作用
目的：探讨在应用阿司匹林,氯比格雷,肝素的基础上,优化的替罗非班临床应用策略对急性ST段抬高型心肌梗死(ST elevation myocardial infarction, STEMI)患者直接经皮冠状动脉介入治疗(primary percutaneous coronary intervention, pPCI)后心肌灌注的作用。
方法：从2009年10月到2010年10月,入住我科行直接PCI的195名STEMI患者,随机分到研究组(n=99)和对照组(n=96)。所有的患者在急诊室确诊为急性ST段抬高型心肌梗死后,立即给予阿司匹林,氯比格雷,肝素及替罗非班(上游应用,10μg/kg3分钟内缓慢静推,继而以0.15μg·kg-1·min-1的速率维持静点)等药物治疗。研究组的患者在开通冠脉前向血流即刻冠脉内再次给予负荷量替罗非班(冠脉内应用,15μg/kg3分钟内缓慢推注)。对照组的患者以同样的方法冠脉内给予等剂量的生理盐水做对照。评价PCI术后心肌梗死溶栓治疗(thrombolysis in myocardial infarction, TIMI)分级、校正的TIMI血流计帧数(Corrected TIMI Frame Count, CTFC)、心肌梗死溶栓治疗心肌灌注分级(TIMI myocardial perfusion grade, TMPG)和主要心脏不良事件(major adverse cardiac events, MACE)的发生情况。所有患者PCI术后给予标准的药物治疗。
结果：1.两组患者基本临床资料的比较：两组患者在年龄、性别、高血压史,糖尿病史、高脂血症、吸烟史、Killip分级、症状发生至球囊开通时间、首次应用替罗非班至球囊开通时间、入院时收缩压,舒张压、心率方面没有统计学差异,但研究组CK峰值(2157.3±1250.1U/L vs.2573.9±1423.6U/L, P=0.031)及CK-MB峰值(197.±120.1U/L vs.243.9±143.6U/L, P=0.024)明显低于对照组。
2.两组患者造影及PCI结果的比较：两组患者在梗死相关血管的分布,多支血管病变的发生情况,术前靶血管的心肌梗死溶栓治疗(Thrombolysis in Myocardial Infarction, TIMI)分级方面无统计学差异。两组患者之间支架的长度和直径也没有统计学意义。尽管两组患者血栓负荷和血栓抽吸方面没有统计学意义,但是研究组患者发生血栓栓塞的情况明显低于对照组(5.1%vs.15.6%,P=0.015)。研究组患者达到TIMI3级(91.9%vs.80.2%,P=0.018)及心肌梗死溶栓治疗心肌灌注分级(TIMI myocardial perfusion grade, TMPG)3级(72.7%vs.52.1%,P=0.003)的比例明显高于对照组。研究组中有91例(91.9%)的患者达到了TIMI3级,而对照组只有77例(80.2%)患者达到TIMI3级水平。研究组中有72例(72.7%)的患者达到了TMPG3级,而对照组只有50例(52.1%)患者达到TMPG3级水平。研究组患者校正的TIMI血流计帧数(Corrected TIMI Frame Count, CTFC)明显低于对照组(19±8vs.22±9,P=0.015)。多元Logistic回归分析显示：血栓负荷(odds ratio [OR],2.54;95%CI,1.18to5.49; P=0.017), PCI术前TIMI血流(OR,0.73;95%CI,0.56to0.96; P=0.022)和冠脉内应用替罗非班(OR,0.31;95%CI,0.15to0.65; P=0.002)是TMPG的独立预测因素。
3.30天的随访结果显示：研究组主要心脏不良事件(major adverse cardiac events, MACE)的发生明显低于对照组(P=0.030),左室射血分数明显高于对照组(56.3±10.0%vs.51.7±7.4%,P=0.016)。两组患者出血并发症相似(P=0.621)。
结论：1.在应用阿司匹林、氯比格雷和肝素的基础上,上游加冠脉内应用高剂量替罗非班可以明显改善急性ST段抬高型心肌梗死患者直接PCI术后心肌组织灌注。
2.上游加冠脉内应用高剂量替罗非班可以改善患者30天的心功能,减低MACE发生。
3.上游加冠脉内应用高剂量替罗非班不增加出血风险。
第四部分
预防性冠脉内应用山莨菪碱对急性ST段抬高型心肌梗死患者直接经皮冠脉介入治疗后心肌灌注的改善作用
目的：临床研究显示冠脉内应用山莨菪碱可以逆转急性ST段抬高型心肌梗死(ST elevation myocardial infarction, STEMI)患者直接经皮冠状动脉介入治疗(primary percutaneous coronary intervention, pPCI)后无复流,改善心肌灌注,从而挽救濒死心肌。本研究的目的是评价预防性冠脉内应用山莨菪碱对STEMI患者直接PCI后心肌灌注的作用。
方法：从2011年1月到2012年1月,于我院行直接PCI的186名急性心肌梗死患者入选本研究,入选患者被随机分到山莨菪碱组(山莨菪碱组,ANI, n=95)或对照组(对照组,CON, n=91)。所有的患者在急诊室确诊为急性ST段抬高型心肌梗死后,立即给予阿司匹林,氯比格雷,肝素及替罗非班(10μg/kg3分钟内缓慢静推,继而以0.15μg·kg-1·min-1的速率维持静点)等药物治疗。山莨菪碱组患者在球囊扩张前冠脉内给予山莨菪碱(2mg,10ml),然后立即行PCI治疗,对照组患者则以同样的方法在冠脉内给予生理盐水。评价PCI术后心肌梗死溶栓治疗(thrombolysis in myocardial infarction, TIMI)分级、校正的TIMI血流计帧数(Corrected TIMI Frame Count, CTFC),心肌梗死溶栓治疗心肌灌注分级(TIMImyocardial perfusion grade, TMPG)和主要心脏不良事件(major adverse cardiac events, MACE)的发生情况。所有患者PCI术后给予标准的药物治疗。
结果：1.两组患者基本临床资料的比较：两组患者在年龄、性别、高血压史,糖尿病史、高脂血症、吸烟史、血管再通时间、入院时收缩压,舒张压、心率方面没有统计学差异,但山莨菪碱组CK峰值(2125.4±1510.1U/L vs.2566.8±1441.5U/L, P=0.042)及CK-MB峰值(162.7±101.5U/L vs.201.4±137.9U/L,P=0.030)水平明显低于对照组。
2.两组患者在梗死相关血管分布,术前血栓负荷,术前TIMI血流,支架的长度和直径方面没有统计学差异。山莨菪碱组患者PCI术后TIMI、 CTFC和TMPG明显好于对照组(P值分别为0.040、0.016和0.005)。山莨菪碱组中有87例(91.6%)的患者达到了TIMI3级,而对照组只有74例(81.3%)患者达到TIMI3级水平。山莨菪碱组中有71例(74.7%)的患者达到了TMPG3级,而对照组只有50例(54.9%)患者达到TMPG3级水平。山莨菪碱组患者CTFC的水平明显低于对照组(20±8vs.23±8,P=0.016)。虽然应用山莨菪碱后患者心率有所增加,但冠脉应用山莨菪碱期间和山莨菪碱后没有心律失常发生。多因素回归分析显示：冠脉内应用山莨菪碱(OR,0.34；95％CI,0.15to0.74；p=0.007),PCI术前TIMI血流(OR,0.67；95％CI,0.44to0.85；p=0.012),血栓负荷(OR,2.60；95％CI,1.11to6.09；P=0.029)是TMPG的独立预测因素。
3.30天随访结果。冠脉内预防性应用山莨菪碱显示了良好的安全性,山莨菪碱组患者30天的MACE发生明显低于对照组(P=0.036)。左室射血分数明显高于对照组(P=0.011)。
结论：1冠脉内预防性应用山莨菪碱可以改善急性ST段抬高型心肌梗死患者直接PCI后的心肌灌注水平.
2冠脉内预防性应用山莨菪碱改善患者心室功能,减低MACE发生。
3冠脉内应用山莨菪碱安全性良好。
With the development of modern medicine, early reperfusion therapy, especially primary percutaneous coronary intervention (pPCI) has become the cornerstone treatment for patients with acute ST-segment elevation myocardial infarction (STEMI), which is the most effective way to save the ischemic myocardium, reduce infarct size, prevent left ventricular remodeling, improve cardiac function, and to reduce mortality. However, in30%to40%of patients, the re-opening of the infarct-related artery did not lead to the improvement of myocardial tissue perfusion, named "poor myocardial perfusion". The mechanism of poor myocardial perfusion is not clear, a large number of clinical studies and animal experiments showed that distal embolization, thrombosis, ischemic related injury, ischemia-reperfusion injury, inflammatory are the causes of poor myocardial perfusion. Recently, a large number of clinical studies have shown that the poor myocardial perfusion is a predictor of myocardial perfusion dysfunction, infarct area extension, ventricular remodeling, heart dysfunction, malignant ventricular arrhythmias, serious complications and long-term mortality. Therefore, early detection, prevention and treatment of poor myocardial perfusion are the common focus in interventional cardiology. Contrast-induced nephropathy (CIN) is another common problem in interventional cardiology. The overall incidence of CIN in the general population has been estimated to lie between1%-6%. Compared to the general population, the incidence in patients with STEMI is considerably higher, which is about19%.
Results from several large clinical trials suggested that platelet GP Ⅱb/Ⅲa inhibitors could significantly improve reperfusion of infarct area and clinical outcomes of patients with STEMI. Meanwhile, intracoronary administration of platelet GP Ⅱb/Ⅲa inhibitors will increase the drug's concentration in the infarct related artery, which may inhibits platelet activation and achieves optimal platelet inhibition. Intracoronary administration of platelet GP Ⅱb/Ⅲa inhibitors may also facilitate the diffusion of them to platelets inside flow-limiting thrombi, resulting in an improved dissolution of thrombi and microemboli at the culprit lesion and in the distal microcirculation, which may be related with improved myocardial perfusion. However, the optimal administration strategy for these agents in this setting remains unclear. In addition, our previous study showed intracoronary anisodamine administered has been proved to be effective in reversing no reflow during primary PCI and improving microvascular perfusion and myocardial salvage. However, once no reflow occurs, it is difficult for pharmacologic agents to reach the microvasculature and take effect. Therefore, this study was done from a prevention perspective to observe the the preventive effect of tirofiban and anisodamine for STEMI patients undergoing primary PCI, and provide a reference for the early optimal myocardial perfusion in clinical practice.
This study was designed to analysis the risk factors of poor myocardial tissue perfusion and CIN in patients with STEMI by retrospectively analysis of clinical data, coronary angiography and intervention results. The protective effect of tirofiban and anisodamine for patients with STEMI were investigated by randomized controlled study.
The detailed methods and results of our study are as follows:
Part Ⅰ
The predictive factors and prognosis effects of poor myocardial perfusion after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction
Objectives:To explore the predictive factors and prognosis effects of poor myocardial perfusion after primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).
Methods:We retrospectively analyzed a total of386consecutive patients (322male and64female) with STEMI who underwent primary PCI within12h of symptom onset from January2007to January2009in this study. Patients were divided into three groups according to angiographic perfusion score:full perfusion group (APS total score10-12, n=140), partial perfusion group (APS total score4-9, n=218) and failed perfusion group (APS total score0-3, n=28). The basic clinical characteristics, angiographic findings and intervention results between these three groups were compared, and multivariate logistic regression analysis was performed to analyze the predictive factors of poor myocardial perfusion after primary PCI in patients with STEMI. Besides, the major adverse cardiac events (MACE) of the patients in the three groups, including cardiac deaths, recurrent nonfatal myocardial infarction, and target vessel revascularization, were observed in hospital and follow-up period. The prognosis effects of poor myocardial perfusion after primary PCI in STEMI were analyzed.
Results:1. There were no significant differences between the three groups with respect to age, gender, hypertension, hypercholesterolemia, diabetes, smoking, systolic blood pressure, diastolic blood pressure, heart rates on admission (all P value>0.05). Among the clinical factors, the time from symptom onset to balloon was shorter in full perfusion group(6.5±2.9h vs.7.4±2.8h vs.8.1±2.6, P=0.014) than that in partial perfusion group and failed perfusion group. The incidence of pre-infarction angina (42.1%vs.28.4%vs.25.0%, P=0.006) was higher in full perfusion group than that in partial perfusion group and failed perfusion group, but there was no significant differences between the partial perfusion group and failed perfusion group. The ratio of tirofiban administration (64.3%vs.53.2%vs.42.9%, P=0.037) was higher in full perfusion group than that in partial perfusion group and failed perfusion group. The ratio of patients with Killip grade≥Ⅱ was higher in failed perfusion group and partial perfusion group than that in full perfusion group (23.6%vs.39.9%vs.46.4%, P=0.003), but there was no significant differences between the partial perfusion group and failed perfusion group. The level of serum glucose on admission was higher in failed perfusion group than that in partial perfusion group and full perfusion group (9.2±3.6mmol/L vs.8.6±2.8mmol/L vs.7.7±3.2mmol/L, P=0.001), the peak CK (2851±1386U/L vs.2673±1452U/L vs.2436±1328U/L, P=0.026) and CK-MB (259±129U/L vs.236±151U/L vs.218±142U/L, P=0.018) level were also higher in failed perfusion group.
2. Angiographic studies demonstrated no significant differences in the incidence of collateral circulation and multivessel disease between the three groups. The ratio of LAD related infarction was much higher in failed perfusion group (71.4%vs.62.8%vs.58.6%, P=0.036) than that in partial perfusion group and full perfusion group. The proportion of visible thrombus was higher in failed perfusion group than that in partial perfusion group and full perfusion group (64.3%vs.49.4%vs.33.3%, P=0.002).
3. Multivariate logistic regression analysis showed that pre-infarction angina, the level of serum glucose on admission, the time from symptom onset to balloon, visible thrombus, tirofiban administration were the independent predictive factors of myocardial perfusion after primary PCI in patients with STEMI. Compared to full myocardial perfusion group, the incidence of MACE was higher in partial perfusion groups and the failed perfusion group.
Conclusions:
1. Pre-infarction angina, hyperglycemia on admission, the time from symptom onset to balloon, visible thrombus, tirofiban administration were the independent predicting factors of APS after primary PCI in patients with STEMI.
2. The incidence of MACE was higher in the poor perfusion group than that in normal perfusion groups.
Part II
Prediction of contrast-induced nephropathy in ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention:role of the ratio of contrast medium volume to estimated glomerular filtration rate
Objective:This study was designed to assess the predictive role of the ratio of contrast medium volume to estimated glomerular filtration rate (CMV/eGFR) in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) who developed contrast-induced nephropathy (CIN).
Methods:We retrospectively investigated clinical factors associated with the development of CIN in114STEMI patients who had undergone primary PCI. The risk factors for CIN included age, gender, body mass index (BMI), left ventricular ejection fraction (LVEF), hemoglobin (Hb), volume of contrast medium, basic levels of serum creatinine (Scr), the number of treated vessels and the number of stents used. We conducted a stepwise regression analysis to evaluate the predictive role of these risk factors in the incidence of CIN.
Results:1. The incidence of CIN was18.4%(21/114). There were no significant differences in age, gender, BMI, LVEF, Hb and incidence of hypertension in patients between the CIN (n=21) and the non-CIN (n=93) groups.
2. The eGFR was significantly lower ((72.0±12.5) ml·min-1·1.73m-2vs.(82.0±16.5) ml·min-1·1.7m-2, P=0.010), and the basic serum creatinine level ((1.07±0.12) mg/dl vs.(0.97±0.19) mg/dl P=0.014) was significantly higher in the CIN group. In addition, the volume of contrast medium was significantly larger ((253±75) ml vs.(211±71) ml, P=0.017) and the CMV/eGFR ratio was significantly greater (3.64±1.26vs.2.70±1.11, P=0.001) in the CIN group.
3. Stepwise regression analysis showed that the CMV/eGFR ratio was a significant independent predictor for the development of CIN (P=0.001). At a cut-off point of>3.1, the CMV/eGFR ratio exhibited71%sensitivity and70%specificity for detecting CIN.
Conclusions:
1. The CMV/eGFR ratio could be a valuable predictor of CIN for STEMI patients after primary PCI.
2. The CMV/eGFR ratio was an optimal predictor for the incidence of CIN at a cut-off point of>3.1,
Part III
New strategy of tirofiban administration improve myocardial perfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention
Objectives:To evaluate the effect of a new regimen of high bolus tirofiban administration on the myocardial perfusion on top of aspirin, clopidogrel and heparin.
Methods:From October2009to October2010, A total of195consecutive patients with STEMI eligible for primary percutaneous coronary intervention (pPCI) were randomly assigned to either study group (n=99) or control group (n=96). All patients in the two groups were pretreated with aspirin, clopidogrel, heparin, and intravenous tirofiban (upstream,10μg/kg over3min as a bolus, then followed by maintenance intravenous tirofiban infusion at0.15μg·kg-1·min-1for24h) in the emergency room immediately after diagnosis was confirmed. Patients in the study group recieved additional bolus tirofiban (intracoronary,15μg/kg over3min) injection immediately after first restoration of antegrade flow, while patients in the control group received intracoronary administration of0.9%sodium chloride of the same volume as study group in the same way. Angiographic analysis included initial and final TIMI grade flow, corrected TIMI frame count, and TIMI myocardial perfusion grade of the culprit vessel. Distal embolism in the targeted vessels was evaluated following PCI. These parameters above were assessed by two independent cardiologists who were blinded to the procedures. All patients in the two groups received standard theraphy after PCI.
Results:1. The two groups were well matched with respect to age, gender, history, high risk factors, Killip classification, time from symptom onset to balloon, initial tirofiban bolus to balloon time, blood pressure, heart rate, but peak CK (2157.3±1250.1U/L vs.2573.9±1423.6U/L, P=0.031) and CK-MB (197±120.1U/L vs.243.9±143.6U/L,P=0.024) levels were lower in anisodamine group
2. Angiographic studies demonstrated no significant differences in the distribution of infarct-related vessel, incidence of multivessel disease, pre-interventional TIMI flow grades between the two groups. The length and diameter of stent were also similar between the two groups. Although the visible thrombus and thrombus aspiration were similar between the two groups, the incidence of distal embolism was lower in the study group (5.1%vs.15.6%, P=0.015). Patients in the study group had better Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count(CTFC), and TIMI myocardial perfusion grade (TMPG) than the subjects in the control group (P=0.018, P=0.015and P=0.003, respectively). TIMI flow grade3was observed in91patients (91.9%) of the study group and in77(80.2%) of the control subjects (P=0.018). CTFC was significantly lower in the ANI group (19±8vs.22±9, P=0.015). TMPG3was seen in72patients (72.7%) of study group and in50(52.1%) of the control subjects (P=0.003). The results of multiple logistic regression showed that visible thrombus (odds ratio [OR],2.54;95%CI,1.18to5.49; P=0.017), pre-PCI TIMI flow (OR,0.73;95%CI,0.56to0.96; P=0.022) and intracoronary tirofiban (OR,0.31;95%CI,0.15to0.65; P=0.002) were all independent predictors of TMPG.
3. Left ventricular ejection fraction was higher in the study group at30 days (56.3±10.0%vs.51.7±7.4%, P=0.016), while the incidence of major adverse cardiac events was lower (P=0.030). The bleeding complications were similar between the two groups during hospitalization and30days follow-up.
Conclusions:1. Upstream plus intracoronary administration of high bolus tirofiban on top of aspirin, clopidogrel and heparin improves myocardial perfusion for STEMI patients undergoing primary percutaneous coronary intervention.
2. Upstream plus intracoronary administration of high bolus tirofiban improve left ventricular ejection fraction, reduces the incidence of major adverse cardiac events.
3. Upstream plus intracoronary administration of high bolus tirofiban doesn't increase major bleeding.
Part IV
Preventively intracoronary administration of anisodamine improves myocardial perfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention
Objectives:Intracoronary anisodamine have been administered for reversing no reflow during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) and have been shown to improve microvascular perfusion and myocardial salvage. This study was designed to evaluate preventively administration of intracoronary anisodamine on myocardial perfusion in terms of slow/no reflow during primary PCI.
Methods:From January2011to January2012, a total of186patients underwent primary PCI within12hours from the onset of STEMI were enrolled. Eligible patients were randomly assigned to receive anisodamine (anisodamine group, ANI, n=95) or placebo (control group, CON, n=91). All patients in the two groups were pretreated with aspirin, clopidogrel, heparin, and intravenous tirofiban (10μg/kg over3min as a bolus, then followed by maintenance intravenous tirofiban infusion at0.15μg·kg-1·min-1for24h) in the emergency room immediately after diagnosis was confirmed. Intracoronary anisodamine (2mg,10ml) was administered immediately prior to balloon inflation and at short intervals during the procedure thereafter, while patients in CON group received intracoronary administration of0.9%sodium chloride with the same volume as ANI group (10ml) in the same way. Angiographic analysis included initial and final TIMI grade flow, corrected TIMI frame count, and TIMI myocardial perfusion grade of the culprit vessel. These parameters above were assessed by two independent cardiologists who were blinded to the procedures. All patients in the two groups received standard theraphy after PCI.
Results:1. The two groups had similar clinical characteristics. No significant differences were demonstrated between the two groups with regards to age, gender, history, high risk factors, Killip classification, time from symptom onset to PCI, left ventricular ejection fraction (LVEF), blood pressure, heart rate, but peak CK (2125.4±1510.1U/L vs.2566.8±1441.5U/L, P=0.042) and CK-MB (162.7±101.5U/L vs.201.4±137.9U/L,P=0.030) levels were lower in anisodamine group.
2. There were no significant differences between the two groups with respect to the distribution of IRA, the length and the diameter of stents. Both groups had similar pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow grade and visible thrombus. The patients treated with intracoronary anisodamine had better post-PCI TIMI flow grade, corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) than those in the control group(P=0.040, P=0.016, and P=0.005, respectively). TIMI flow grade3was observed in87of the patients (91.6%) who received intracoronary anisodamine and in74of the control subjects (81.3%) who received placebo (P=0.040). CTFC was significantly lower in the ANI group (20±8vs.23±8, P=0.016). TMPG3was seen in71of the patients (74.7%) who received intracoronary anisodamine and in50of the control subjects (54.9%) who received placebo (P=0.005). Although patients' heart rates increased after administration of anisodamine, no tachyarrhythmia happened during and after anisodamine administration. Multiple logistic regression analysis found that intracoronary anisodamine (OR,0.34;95%CI,0.15to0.74; P=0.007), initial TIMI flow (OR,0.67;95%CI,0.44to0.85; P=0.012), visible thrombus (OR,2.60;95%CI,1.11to6.09; P=0.029) were independent predictors of TMPG。
3. Compared with control group, intracoronary anisodamine showed a good safety and the incidence of MACE was significantly lower in the ANI group during30days follow-up (P=0.036). Left ventricular ejection fraction was higher in the study group during30days follow-up (P=0.011).
Conclusions:1Intracoronary administration of anisodamine immediately prior to balloon inflation improves postprocedural myocardial perfusion for STEMI patients undergoing primary percutaneous coronary intervention.
2Intracoronary administration of anisodamine improves left ventricular function and reduces MACE at30days.
3Intracoronary administration of anisodamine is safe, with few side effects.
引文
1 De Luca, Suryapranata H, Marino P. Reperfusion strategies in acute ST-elevation myocardial infarction:an overview of current status [J]. Progress in Cardiovascular Diseases,2008,50:352-382
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