ST-segment resolution 60 minutes after combination treatment of abciximab with reteplase or reteplase alone for acute myocardial infarction (30-day mortality results from the resolution of ST-segment after reperfusion therapy substudy)

The combination of abciximab with thrombolytic therapy when treating acute ST-elevation myocardial infarction has been hypothesized to enhance microvascular perfusion. Resolution of ST-segment elevation after thrombolytic therapy is believed to be a marker of myocardial reperfusion and to predict mortality rate. Among 16,588 patients enrolled in the Fifth Global Use of Strategies to Open Occluded Arteries in Acute Myocardial Infarction trial, 1,764 consecutive patients from selected centers had their study electrocardiograms evaluated by a core laboratory for ST-segment deviation resolution 60 minutes after treatment. Patients were categorized into 4 groups: complete resolution (>70%), partial resolution (<70% to 30%), no resolution (<30%), and worsening ST-segment deviation. Patients treated with reteplase or a combination of reteplase plus abciximab had similar rates of complete resolution (32% vs 34%), partial resolution (29% vs 27%), no resolution (15% vs 16%), and worsening ST-segment elevation (23 vs 23%; p = 0.59). The 30-day mortality rates in these 4 groups were 2.1%, 5.2%, 5.5%, and 8.1% (p <0.001). Even after accounting for baseline variables, incomplete ST-segment resolution (<70%) was associated with an increased risk of death within 30 days (adjusted hazard ratio 2.41, 95% confidence interval 1.25 to 4.63, p <0.008). Thus, ST-segment resolution at 60 minutes was no different in patients treated with full-dose reteplase from those treated with a combination of abciximab and reteplase. Patients with >70% ST-segment resolution within 60 minutes had markedly decreased mortality rates, irrespective of treatment.     

The level I cardiovascular center: is it time?

There is no uniform approach to treating the 1.5 million US citizens who have an acute myocardial infarction (AMI) each year. This contrasts with the trauma system developed to efficiently triage and treat the critically injured accident victim. Only two thirds of patients with ST-segment elevation AMI in the United States are treated with thrombolytic therapy or primary angioplasty (percutaneous coronary intervention [PCI]) which can reduce the 30-day mortality rate from approximately 15% to 6%-10%. The Early Retavase-Thrombolysis in Myocardial Infarction (ER-TIMI) 19 trial demonstrated that AMI patients who received prehospital thrombolytic therapy and were brought to the nearest receiving hospital experienced a 32-minute reduction in the time to treatment and time to ST-elevation resolution compared with those treated at their time of hospital arrival. This expedited therapy was associated with a low in hospital mortality rate (4.7%). The potential benefit of facilitated PCI with partial-dose thrombolysis and abciximab administration was demonstrated by the Strategies for Patency Enhancement in the Emergency Department (SPEED) investigators who found that double bolus recombinant plasminogen activator (reteplase) (5 + 5 megaunits) and abciximab with the addition of early PCI, resulted in a final infarct-related artery TIMI 3 flow rate of 86% compared with 77% with combination therapy alone. The Primary Angioplasty in Acute Myocardial Infarction (PAMI) investigators have shown that patients admitted with infarct-related artery TIMI 3 flow at the time of primary PCI had less than a 1% 6-month mortality. Treating AMI patients with prehospital, partial dose thrombolysis followed by immediate transport to a Level I cardiovascular center (bypassing the closest hospital if necessary) for facilitated infarct-related artery PCI has the potential to reduce the mortality in ST-elevation AMI patients from 6%-10% to less than 4% which could translate into saving approximately 500 lives per day in the United States. It is time to validate this strategy with a randomized clinical trial, the Prehospital Administration of Thrombolytic Therapy With Urgent Culprit Artery Revascularization trial (PATCAR).     

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.     

Early coronary intervention following pharmacologic therapy for acute myocardial infarction (the combined TIMI 10B-TIMI 14 experience).

Earlier studies have suggested that immediate percutaneous coronary intervention (PCI) following thrombolytic therapy for acute myocardial infarction (AMI) is associated with an increase in adverse events and that routine PCI in this setting has offered no advantage over a conservative strategy. To reassess this issue in a more recent era, we evaluated 1,938 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B and 14 trials of AMI. Patients in TIMI 10B were randomized to receive tissue plasminogen activator or TNK tissue plasminogen activator, whereas patients in TIMI 14B trial were randomized to receive thrombolytic therapy with or without abciximab. All patients underwent angiography 90 minutes after receiving pharmacologic therapy. Patients who underwent PCI were classified as having undergone a rescue procedure (TIMI 0 or 1 flow at 90 minutes), an adjunctive procedure (TIMI 2 or 3 flow at 90 minutes), or a delayed procedure (performed >150 minutes after symptom onset, median of 2.75 days). Among patients with TIMI 0 or 1 flow, there was a trend for lower 30-day mortality among patients who underwent rescue PCI than among those who did not (6% vs 17%, p = 0.01, adjusted p = 0.28). Patients who underwent adjunctive PCI had similar 30-day mortality and/or reinfarction as those who underwent delayed PCI. In a multivariate model both had lower 30-day mortality and/or reinfarction than patients with "successful thrombolysis" (i.e., TIMI 3 flow at 90 minutes) who did not undergo revascularization (p = 0.02). Thus, early PCI following AMI is associated with excellent outcomes. Randomized trials of an early invasive strategy following thrombolysis are warranted.     

急性冠状动脉支架成形术后心肌组织灌注的临床研究

目的 观察急性心肌梗死患者冠状动脉介入(PCI)治疗成功后，校正的TIMI帧数(CTFC)与心电图ST段回落联合评价心肌组织水平灌注的可行性。方法 测定PCI治疗后血流达。TIMI3级患者的CTFC，并在术前及术后1个月分别测定室壁运动记分(WMSI)。观察CTFC与WMSI之间的相关性，同时检查术前及术后1小时心电图ST段回落情况。结果 按照CTFC将，TIMI血流3级者分为快、慢两组，快CTFC组患者ST段回落程度明显优于慢CTFC组；1个月后快CTFC组患者的室壁运动记分改善程度明显优于慢CTFC组，CTFC与术前、术后WMSI的差值有明显的负相关；快CTFC组患者从发病到接受PCI治疗的时间明显短于慢CTFC组。结论 CTFC作为一种定量、客观、简单、经济、重复性好的方法评价心肌微循环灌注情况，较低的CTFC及心电图ST段回落完全预示着良好的心功能恢复，可为临床提供是否需要进一步辅助治疗的证据。     

校正TIMI帧数与ST段回落评价老年急性心肌梗死患者支架成形术后心肌组织灌注

目的　观察老年急性心肌梗死 (AMI)患者冠状动脉介入 (PCI)治疗成功后 ,校正的 TIMI帧数 (CTFC)与心电图 ST段回落联合评价心肌组织水平灌注的可行性。方法　选取接受 PCI治疗后血流达 TIMI3级的老年 AMI患者 42例 ,测定 CTFC,并在术前及术后 1月分别测定室壁运动记分 (WMSI)。观察 CTFC与 WMSI之间的相关性 ,同时检查术前及术后 1 h心电图 ST段回落情况。结果　按照 CTFC将 TIMI血流 3级者分为快、慢两组 ,快 CTFC组 ST段回落程度明显优于慢 CTFC组 ;一个月后快 CTFC组的 WMSI改善程度明显优于慢 CTFC组 ,CTFC与术前、术后WMSI的差值有明显的负相关 ;快 CTFC组患者从发病到接受 PCI治疗的时间明显短于慢 CTFC组。结论　 CTFC作为一种定量、客观、简单、经济、重复性好的方法评价心肌微循环灌注情况 ,较低的 CTFC及心电图 ST段回落完全预示着良好的心功能恢复及临床预后 ,可为临床提供是否需要进一步辅助治疗的依据。     

Electrocardiographic diagnosis of reperfusion during thrombolytic therapy in acute myocardial infarction

Continuous 12-lead electrocardiographic monitoring was performed in 61 patients receiving thrombolytic therapy for an acute myocardial infarction. Coronary angiography within 90 minutes revealed a patent vessel (Thrombolysis in Myocardial Infarction [TIMI] trial 2 or 3) in 44 patients. Early signs of reperfusion were ST-segment normalization (likelihood ratio 16.0), development of terminal T-wave inversion (likelihood ratio 10.6), accelerated idioventricular rhythm (likelihood ratio 6.0), and a twofold increase in ventricular premature complexes (likelihood ratio 2.5). Relief of chest pain after 60 minutes was reported by 96%. During reperfusion of the infarct-related vessel, an increase in ST-segment deviation was recorded in 61% of the patients, whereas 69% had an increase in chest pain preceding the eventual decline.     

急性心肌梗死直接与联合冠状动脉入治疗的比较

目的比较尿激酶静脉溶栓联合冠状动脉(冠脉)介入治疗(PCI)术与直接PCI术对急性心肌梗死(AMI)的有效性和安全性。方法64例首次ST段抬高AMI(STelevationmyocarialinfarc-tion,STEMI)患者随机分为直接PCI组(直接PCI治疗)和联合PCI组(在尿激酶静脉溶栓基础上联合直接PCI治疗)。PCI术治疗前后行冠脉造影、心电图检查,观察梗死相关血管(IRA)前向血流,测定心肌梗死溶栓治疗临床试验(TIMI)血流、TIMI心肌灌注分级(TMPG),计算冠脉造影灌注积分(APS)和心电图ST段回落程度,评估心外膜血管和心肌灌注情况,对两组患者介入术前IRA通畅率、住院期间出血并发症、急性缺血事件发生率及出院前左心室功能进行比较。用线性回归分析评价ST段回落程度与APS的相关性。结果PCI术前联合PCI组冠脉再通率显著高于直接PCI组(68.8%比37.6%,P<0.05),其中完全再通率在两组间比较差异有统计学意义(46.9%比21.9%,P<0.05);联合PCI组心肌再灌注率显著高于直接PCI组(71.9%比37.4%,P<0.01),其中完全心肌再灌注率在两组间比较差异有统计学意义(46.9%比21.9%,P<0.05)。PCI术后两组IRA的TIMI血流3级比较差异无统计学意义(90.6%比87.5%,P>0.05),但比较TMPG差异有统计学意义(93.8%比75.0%,P<0.05),其中TMP3级有明显差异(65.6%比37.5%,P<0.05);联合PCI组APS10~12分(心肌完全再灌注)与直接PCI组比较差异有统计学意义(P<0.01)。介入治疗后出院前联合PCI组的LVEF值明显大于直接PCI组。联合PCI组ST段完全回落比例明显高于直接PCI组。线性回归分析评价ST段回落程度与APS之间有显著相关性(相关系数r=0.961,P<0.001),住院期间两组均无死亡病例、严重出血及急性缺血事件发生。结论联合PCI术较直接PCI术可获得更好的IRA开通、心肌组织和微循环灌注及心功能的明显改善。APS结合TIMI血流分级和TMPG可较好地完整评价心外膜血管和心肌灌注情况,并与心电图ST段回落程度有显著相关性。     

Changes in standard electrocardiographic ST-segment elevation predictive of successful reperfusion in acute myocardial infarction

The ability of the electrocardiographic ST segment to predict successful reperfusion after thrombolytic therapy remains controversial. To evaluate whether angiographically determined reperfusion could be predicted from changes in ST-segment elevation, the sum of ST-segment elevation in affected leads of the electrocardiogram was compared before and after thrombolytic therapy in 53 patients with acute myocardial infarction (AMI). Reperfusion status of the infarct-related artery was determined angiographically less than 8 hours from onset of symptoms. According to the Thrombolysis in Myocardial Infarction trial (TIMI) criteria, 33 patients had successful reperfusion (TIMI grade 2 to 3 flow) after thrombolytic therapy and 20 patients did not (TIMI grade 0 to 1 flow). Logistic multiple regression analysis showed that the proportional value for the shift in the sum of ST elevation, termed the "% ST change," was more strongly associated with reperfusion than the absolute measured difference in millimeters (chi-square = 11.34 vs 9.22). The entire spectra of sensitivities and specificities were determined to identify a level of the percent ST change with simultaneous high sensitivity and specificity. A 20% decrease in ST elevation provided such a level (88% sensitivity, 80% specificity). The positive and negative predictive values of a 20% decrease in ST elevation were 88 and 80%, respectively. These results suggest that a decrease of only 20% in the sum of ST elevation in the standard electrocardiogram after thrombolytic therapy is a useful noninvasive predictor of reperfusion status in patients with evolving AMI.     

Predicting outcome after thrombolysis in acute myocardial infarction according to ST-segment resolution at 90 minutes: a substudy of the GUSTO-III trial. Global Use of Strategies To Open occluded coronary arteries

Background Resolution of ST-segment elevation after thrombolysis for acute myocardial infarction has been shown to have prognostic significance 3 hours (180 minutes) after the initiation of therapy. Whether prognostically useful information can be achieved as early as 90 minutes after thrombolysis is unknown. Methods An electrocardiographic substudy of 2352 patients from the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial was undertaken to compare outcomes according to ST-segment resolution at 90 minutes versus 180 minutes after administration of thrombolytic therapy. Results Of 2352 patients in the substudy, 2241 had a baseline and 90-minute electrocardiogram, and 2218 had a baseline and 180-minute ECG. Complete ST-segment resolution occurred in 44.2% of patients at 90 minutes and 56.5% of patients at 180 minutes. ST-segment resolution at both 90 and 180 minutes was associated with lower 30-day and 1-year mortality. Multivariate analysis revealed ST-segment resolution at 90 minutes to be an equally strong predictor of 30-day mortality as resolution at 180 minutes. Patients who were at particularly high risk for mortality were those aged >70 years, those who presented with Killip class >1, and those with anterior infarctions. Conclusions The presence of ST-segment resolution on standard 12-lead electrocardiographic monitoring 90 minutes after thrombolysis is a useful independent predictor of mortality at 30 days and 1 year. The potential for obtaining prognostic results as early as 90 minutes after thrombolysis sets a new precedent for optimum electrocardiographic monitoring times in these patients. (Am Heart J 2002;144:81-8.)     

Effect of preinfarction angina pectoris on microcirculation in patients with reperfused acute myocardial infarction

Preinfarction angina pectoris has been suggested in some studies to have a beneficial effect on left ventricular function after acute myocardial infarction (AMI). The precise mechanisms of this protection have not been fully elucidated. The effect of preinfarction angina on myocardial tissue perfusion also needs to be clarified. In this study, we investigated the influence of preinfarction angina on microvasculatory damage by using ST-segment resolution and pressure-derived collateral flow index (CFIp) as a marker of microcirculatory perfusion. METHODS: We studied 41 patients with a first AMI in whom thrombolysis in myocardial infarction (TIMI) grade 3 flow in the infarct-related artery was established by thrombolytic therapy. The percent resolution of ST-segment deviation (deltasigma ST) after thrombolysis was determined. All of the patients had TIMI grade 3 flow in IRA at the coronary angiography, which was done a mean of 4 days after AMI. Intracoronary pressure measurements and stent implantation to the IRA were performed. After angiography, CFIp was calculated as the ratio of simultaneously measured coronary wedge pressure-central venous pressure (Pv) to mean aortic pressure-Pv. RESULTS: Patients with preinfarction angina pectoris had greater percent deltasigma ST than those without PA (67 +/- 18% vs. 44 +/- 24%, p = 0.03).The mean of the coronary wedge pressure (16.4 +/- 7.4 compared with 23.2 +/- 9.4, P < 0.03) and the pressure-derived collateral flow index (0.15 +/- 0.10 compared with 0.22 +/- 0.08, P < 0.03) were significantly lower in patients with preinfarction angina compared to those without. CONCLUSION: Preinfarction angina is associated with a greater degree of ST-segment resolution and lower CFI-p in patients with TIMI-3 reflow after thrombolysis. These findings suggest that a protective effect of preinfarction angina against reperfusion injury may result in greater ST resolution and lower CFIp after AMI.     

ST-segment analysis to predict infarct size and functional outcome in acute myocardial infarction treated with primary coronary intervention and adjunctive abciximab therapy

ST-segment resolution is used to classify the response to reperfusion therapy in acute myocardial infarction, but the possibility to predict outcome in individual patients is unclear, particularly in the setting of primary percutaneous coronary intervention (PCI) and abciximab therapy. We studied 213 patients who underwent successful revascularization with PCI. Maximal ST-segment elevation was measured before and 30 minutes after PCI. Patient outcome was defined on the basis of infarct size and left ventricular ejection fraction (EF) as derived from gated single-photon emission computed tomography that was acquired 1 month after infarction. Patients who had > or =50% ST resolution showed a smaller infarct (15.1 +/- 13.6% vs 19.9 +/- 15.7%, p < 0.05) but not a higher left ventricular EF (48.7 +/- 12.3% vs 45.2 +/- 11.8%) than did patients who had <50% resolution. According to cluster analysis of infarct size and left ventricular EF, 132 patients had favorable outcome (central values: infarct size 7.5%, left ventricular EF 55%) and 81 did not (central values: infarct size 30%, left ventricular EF 36%). Using receiver-operating characteristic curve analysis, the optimal ST-resolution cutoff was >60%, with 77% sensitivity and 51% specificity for predicting favorable outcome. ST-segment elevation < or =4.5 mV before PCI was 80% sensitive and 48% specific, and ST-segment elevation < or =1 mV after PCI was 74% sensitive and 60% specific for predicting favorable outcome. In conclusion, in the setting of primary PCI and abciximab therapy, ST-segment elevation resolution requires a high threshold (>60%) to effectively classify patients; the capability of ST-segment analysis to predict patient outcome is limited, with ST-segment elevation after PCI showing the best compromise between sensitivity and specificity.     

Angiographic and clinical outcome after percutaneous coronary interventions following combined fibrinolytic therapy in acute myocardial infarction

INTRODUCTION: Combined therapy with fibrinolytic agent and platelet GPIIb/IIIa inhibitor not followed by an interventional procedure does not improve prognosis in patients presenting with acute ST-segment elevation myocardial infarction (STEMI) when compared to fibrinolysis alone. On the other hand, in the past percutaneous coronary interventions (PCI) performed after fibrinolysis were associated with low angiographic efficacy, a high risk of bleeding and a high rate of early cardiovascular events. Aim: Evaluation of angiographic and clinical outcomes in patients with STEMI treated with PCI following combined fibrinolytic therapy. METHODS AND RESULTS: Complete angiographic and clinical data of 187 patients who underwent PCI immediately after combined fibrinolytic therapy were obtained from a survey of 669 consecutive patients with STEMI <12 hours, at age <75 years, without cardiogenic shock, who were transferred from regional hospitals to the catheterisation laboratory within 90 minutes and after the initiation of combined fibrinolytic therapy (alteplase 15 mg iv as a bolus followed by an infusion of 35 mg over 60 minutes; abciximab iv bolus of 0.25 mg/kg followed by a 12 h infusion of 0.125 microg/kg per minute; unfractionated heparin). At baseline angiographic examination revealed no flow (TIMI 0+1) in the infarct-related artery in 17.1% of patients, impaired flow (TIMI 2) in 17.1% and normal (TIMI 3) in 65.8% of cases. After immediate PCI, a significant improvement in epicardial perfusion (TIMI 2+3, 99.5%) and in microcirculation was achieved. This favourable effect was seen only in the group of patients with baseline TIMI 0+1 flow, whereas PCI in the group with baseline TIMI 3 flow did not cause any further improvement in microcirculatory perfusion. The rate of cardiovascular events within the first 30 days and 12 months after the procedures were similar in the studied subgroup of patients. CONCLUSIONS: PCI performed after combined fibrinolytic therapy in STEMI patients is associated with high efficacy and improvement in indices of epicardial perfusion and microcirculation. These benefits are confined mainly to patients with primarily impaired flow in the infarction-related artery (TIMI 0+1). However, the clinical results of this strategy, particularly in patients undergoing PCI following successful combined fibrinolytic therapy, must still be proved in further randomised trials.     

Bleeding risks with abciximab after full-dose thrombolysis in rescue or urgent angioplasty for acute myocardial infarction

BACKGROUND: The bleeding risk associated with platelet glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) after full-dose thrombolysis for acute myocardial infarction (AMI) is unclear. We examined the risk and predictors of bleeding complications in patients with AMI who received abciximab during rescue or urgent PTCA after full-dose thrombolytic therapy. METHODS: A multicenter retrospective cohort of 147 consecutive patients who underwent PTCA within 48 hours after full-dose thrombolysis for AMI was studied. Bleeding events (major, minor, nuisance) from the onset of AMI to discharge were compared between those who received abciximab (n = 57) and those who did not (n = 90). RESULTS: Baseline clinical characteristics were similar between the two groups. Despite lower doses of procedural heparin, the incidence of non-coronary artery bypass graft-related major and minor bleeding was higher in the abciximab group than in controls (63% vs 39%, P =.004). Although the risk of major bleeding was 4-fold with abciximab (12% vs 3%, P =.04), only one intracranial and one fatal bleeding event occurred. Multivariable regression identified abciximab therapy as the most powerful independent predictor of combined major and minor bleeding, with a hazard risk ratio of 1.9 (P =.04). CONCLUSIONS: In the setting of rescue or urgent PTCA within 48 hours after full-dose thrombolytic therapy after AMI, major and particularly minor bleeding were frequently encountered. The adjunctive use of abciximab increased these bleeding risks by approximately 2-fold.     

Relation of corrected thrombolysis in myocardial infarction frame count and ST‐segment resolution to myocardial tissue perfusion after acute myocardial infarction

Objectives : To evaluate myocardial tissue perfusion by corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and ST‐segment resolution after successful percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Background : Early and sustained potency of infarct‐related artery (IRA) has become the main goal of reperfusion therapy in patients with AMI. However, myocardial tissue perfusion may remain impaired even after the achievement of TIMI grade 3 flow of the epicardial artery without residual stenosis. Methods : CTFC was measured after successful PCI in 63 patients with first AMI. The extent of ST‐segment resolution was recorded 1 hr after reperfusion therapy. The wall motion score index (WMSI) was assessed before and 1 month after PCI. Then we studied the correlation between CTFC, ST‐segment resolution, and WMSI. Results : According to CTFC, the patients with TIMI grade 3 flow after PCI were divided into two groups: CTFC fast group and CTFC slow group. CTFC fast group had higher percentage of complete ST resolution (54.1% vs. 25.0%, P < 0.05) and lower percentage of no ST resolution (2.6% vs. 29.2%, P < 0.05). Improvement of WMSI in the CTFC fast group was significantly greater than that of the CTFC slow group (1.30 ± 0.41 vs. 0.64 ± 0.30, P < 0.05). CTFC had a significant negative correlation with the change in WMSI (r = ?0.75, P < 0.01). Conclusions : Combined with ST‐segment resolution, CTFC could predict risk for patients with successful reperfusion therapy after AMI and provide evidence for additional adjunctive treatment. © 2008 Wiley‐Liss, Inc.     

Comparison of reperfusion regimens with or without tirofiban in ST-elevation acute myocardial infarction

There is continued debate as to whether a combined reperfusion regimen with platelet glycoprotein IIb/IIIa inhibitors provides additional benefit in optimal myocardial reperfusion of patients with a ST-elevation acute myocardial infarction (AMI). In addition, the best angiographic method to evaluate optimal myocardial reperfusion is still controversial. Patients (n = 144) with a first AMI presenting <6 hours from onset of symptoms were randomized to receive a conjunctive strategy (n = 72) with low-dose alteplase (50 mg) and tirofiban (0.4 microg/kg/min/30 minute bolus; infusion of 0.1 microg/kg/minute), or tirofiban plus stenting percutaneous coronary intervention (PCI). Control patients (n = 72) received standard strategy with either full-dose alteplase (100 mg) or stenting PCI [correction]. All patients were submitted to coronary angiographic study at 90 minutes. The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow at 90 minutes. Secondary end points were TIMI myocardial perfusion (TMP) rates, a composite end point at 30 days (death, reinfarction, refractory ischemia, stroke, heart failure, revascularization procedures, or pulmonary edema), and bleeding or hematologic variables. The rate of TIMI 3 flow at 90 minutes for patients treated with alteplase alone was 42% compared with 64% for those who received low-dose alteplase and tirofiban. Standard stenting PCI achieved 81% of TIMI 3 flow compared with 92% when tirofiban was used. Significantly higher rates of TMP grade 3 were observed when tirofiban was used as the adjunctive treatment in both alteplase (66% vs 47%) and stenting PCI (73% vs 55%). Higher rates of the composite end point were observed in standard regimens compared with conjunctive regimens (hazard ratio 5.8, 95% confidence interval 1.27 to 26.6, p = 0.023). Regardless of reperfusion regimen, better outcomes were observed when a combination of TIMI 3 flow and TMP grade 3 was achieved. Beyond TIMI 3 flow rate, the TMP grade was an important determinant. The rates of major bleeding were similar (2.8%) for standard versus conjunctive regimens with tirofiban. Thus, tirofiban as a conjunctive therapy for lytic and stenting regimens not only improves TIMI 3 flow rates, but also the TMP3 rates, which are related to a better clinical outcome without an increase in the risk of major bleeding. This study supports the hypothesis that platelets play a key role not only in the atherothrombosis process, but also in the disturbances of microcirculation and tissue perfusion.     

Very early risk stratification after thrombolytic therapy with a bedside myoglobin assay and the 12-lead electrocardiogram

BACKGROUND: Available clinical criteria to estimate prognosis in patients with evolving ST-segment elevation myocardial infarction do not consider the impact of reperfusion therapy and do not incorporate measurement of baseline levels of cardiac serum markers. We evaluated the combination of a baseline myoglobin assay and early (60- to 90-minute) ST resolution for risk stratification after ST-segment elevation myocardial infarction. METHODS: In a prospective substudy of the Intravenous nPA for Treatment of Infarcting Myocardium Early-II (InTIME-II) trial carried out in 2079 patients, a rapid qualitative assay for myoglobin was performed immediately before thrombolysis. Serial 12-lead electrocardiograms were performed at baseline and 60 to 90 minutes after thrombolysis. ST resolution was categorized as complete (>/=70%), partial (30% to <70%), or none (<30%). RESULTS: Mortality rate at 30 days was 3.3% in the 905 patients with a negative baseline myoglobin assay versus 8.9% in the 527 patients with a positive assay (P <.0001). Mortality rate was lowest (2.4%) among the 614 patients with complete ST resolution, intermediate (4.9%) among the 512 patients with partial ST resolution, and highest (8.1%) among the 540 patients with no ST resolution (P <.0001 for trend). In a logistic regression model incorporating other baseline predictors of 30-day mortality rate, both a positive myoglobin assay (relative risk 1.98, 95% confidence interval 1.00-3.90) and ST resolution <70% (relative risk 2.86, 95% confidence interval 1.22-6.69) were independently associated with increased mortality rate. At 30 days, mortality rate was 0.4% among patients with a negative myoglobin assay and complete ST resolution, 4.8% among patients with either a positive myoglobin assay or ST resolution <70%, and 9.6% among those with both a positive myoglobin ratio and ST resolution <70% (P <.001 for trend). CONCLUSIONS: Within 90 minutes after administering thrombolytic therapy for acute myocardial infarction, clinicians can determine the risk for death at the patient's bedside with a hand-held myoglobin assay and 2 serial 12-lead electrocardiograms. A strategy using these 2 simple, rapid, and inexpensive tests may facilitate triage after thrombolytic therapy.     

Angiographic and clinical characteristics associated with the development of Q-wave and non-Q-wave myocardial infarction in the thrombolysis in myocardial infarction (TIMI) 14 trial

Background

In the absence of thrombolytic therapy, patients with non-Q-wave myocardial infarction (MI) have previously been shown to have lower long-term mortality rates than patients with Q-wave MI. The goal of our study was to examine the angiographic and clinical differences between non-Q-wave MI and Q-wave MI in patients with ST elevation MI (STEMI) in the era of thrombolytic and combination therapy of thrombolytics plus glycoprotein IIb/IIIa inhibitors.

Methods

Angiography was performed 90 minutes after thrombolytic administration in the Thrombolysis in Myocardial Infarction (TIMI) 14 trial. The development of a non-Q-wave MI was assessed on electrocardiogram performed at the time of hospital discharge. Angiographic findings were assessed at an angiographic core laboratory by blinded investigators.

Results

The qualifying episode of ST elevation developed into a non-Q-wave MI in 36% of patients (315/878) and into a Q-wave MI in 64% of patients (563/878). In patients in whom non-Q-wave MI developed, the rate of TIMI grade 3 flow was higher, peak creatine kinase level was lower, mean left ventricular ejection fraction was greater, corrected TIMI frame counts (CTFCs) were lower (ie, faster blood flow), and chest pain duration after thrombolytic administration was shorter. Patients in whom non-Q-wave MI developed less frequently underwent a percutaneous coronary intervention (PCI), and when they did, they had faster post-PCI CTFCs and higher rates of post-PCI TIMI grade 3 flow. Patients in whom a non-Q-wave MI developed had lower rates of severe recurrent ischemia. There were no differences in 30-day or in-hospital mortality rates or recurrent MI between patients with Q-wave MI and patients with non-Q-wave MI.

Conclusion

After thrombolytic therapy in STEMI with or without abciximab, ejection fractions were higher, the duration of ischemia was shorter, and coronary blood flow at both 90 minutes and after PCI was faster in patients who sustained non-Q-wave MI than in patients who sustained Q-wave MI. No differences in mortality or recurrent MI rates were detected in patients who sustained a Q-wave MI and patients in whom a Q-wave MI did not evolve in the modern thrombolytic era.     

Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction

OBJECTIVES: We investigated the impact of diabetes mellitus on myocardial perfusion after primary percutaneous coronary intervention (PCI) utilizing myocardial blush grade (MBG) and ST-segment elevation resolution (STR). BACKGROUND: Diabetes is an independent predictor of outcomes after primary PCI for acute myocardial infarction (AMI). Whether the poor prognosis is due to lower rates of myocardial reperfusion is unknown. METHODS: Reperfusion success in those with and without diabetes mellitus was determined by measuring MBG (n = 1,301) and STR analysis (n = 700) in two substudies of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial among patients undergoing primary PCI for AMI. RESULTS: There were no differences between those with or without diabetes with regard to postprocedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 (>95%), distribution of infarct-related artery, and the frequency of stent deployment or abciximab administration. Patients with diabetes mellitus were more likely to have absent myocardial perfusion (MBG 0/1, 56.0% vs. 47.1%, p = 0.01) and absent STR (20.3% vs. 8.1%, p = 0.002). Diabetes mellitus (hazard ratio [HR] 1.63 [95% confidence interval (CI) 1.17 to 2.28], p = 0.004) was an independent predictor of absent myocardial perfusion (MBG 0/1) and absent STR (HR 2.94 [95% CI 1.64 to 5.37], p = 0.005) by multivariate modeling. CONCLUSIONS: Despite similar high rates of TIMI flow grade 3 after primary PCI in patients with and without diabetes, patients with diabetes are more likely to have abnormal myocardial perfusion as assessed by both incomplete STR and reduced MBG. Diminished microvascular perfusion in diabetics after primary PCI may contribute to adverse outcomes.     

Effect of preinfarction angina pectoris on ST-segment resolution after primary coronary angioplasty for acute myocardial infarction

The presence of preinfarction angina has been shown to exert a favorable effect on left ventricular function after acute myocardial infarction (AMI). Whether or not preinfarction angina is beneficial for myocardial tissue reperfusion, however, remains to be determined. We sought to evaluate the influence of preinfarction angina on resolution of ST-segment elevation, which could be affected by microcirculatory damage after recanalization therapy. We studied 96 patients with a first AMI in whom Thrombolysis In Myocardial Infarction (TIMI)-3 flow in the infarct-related artery was established by primary angioplasty. Percent reduction in the sum of ST elevation from baseline to 1 hour after angioplasty (percent delta summation operator ST) was examined. Poor ST resolution, defined as percent delta summation operator ST <50%, was observed in 25 patients, who had a worse clinical outcome, larger infarct size, and poorer left ventricular function. On multivariate analysis, the absence of preinfarction angina, as well as anterior wall infarction, were major independent predictors of poor ST resolution, whereas age, sex, coronary risk factors, ischemic time, Killip class on admission, multivessel disease, initial TIMI flow grade, and extent of collaterals were not significant. Patients with preinfarction angina had a greater degree of ST-segment resolution than those without angina (71 +/- 21% vs 49 +/- 43%, p = 0.02). Additional ST elevation after reperfusion was noted exclusively in patients without preinfarction angina (p = 0.02). Preinfarction angina is associated with a greater degree of ST-segment resolution in patients with TIMI-3 flow after primary angioplasty, suggesting a protective effect of preinfarction angina against microcirculatory damage after reperfusion.