| 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 ⅠThe 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 IIPrediction 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 rateObjective: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 IIINew strategy of tirofiban administration improve myocardial perfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary interventionObjectives: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 group2. 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 IVPreventively intracoronary administration of anisodamine improves myocardial perfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary interventionObjectives: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. |
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