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Aims: To compare dual vs. triple antiplatelet pre-treatment in patients with non-ST-elevation acute coronary syndrome (NSTE ACS) who were planned for early catheterization., Methods and Results: A total of 328 consecutive patients with NSTE ACS were included and were randomized to pre-treatment with dual (n = 166, aspirin, clopidogrel 600 mg) or triple antiplatelet therapy (n = 162, aspirin, clopidogrel 300 mg, and Tirofiban). The primary endpoint was enzymatic infarct size, defined as cumulative LDH release (LDHQ(48)). Initial TIMI flow of the culprit vessel was a pre-specified secondary endpoint. Angiography was performed in 98% of patients at a median of 23 h after admission. Enzymatic infarct size (median, 25-75%) was 166 (60-349) IU/L in the triple group compared with 193 (75-466) IU/L in the dual group (P = 0.2). Initial TIMI 3 flow of the culprit vessel was significantly more often observed after triple antiplatelet therapy (67 vs. 47%, P = 0.002). At 30 days follow-up, myocardial infarction (MI) occurred in 46% of patients in the triple antiplatelet group, compared with 57% in the dual antiplatelet group, P = 0.052. No significant difference in bleeding was present., Conclusion: This study showed that in patients with NSTE ACS, triple antiplatelet pre-treatment was associated with a non-significant reduction in enzymatic infarct size, a significantly better initial perfusion of the culprit vessel, and a trend towards a better survival without death or MI. Further, large-scale studies should be performed to find whether the beneficial trend in favour of triple antiplatelet pre-treatment can be reproduced.

Aims: It is still unknown whether impaired myocardial perfusion helps to explain the higher mortality observed with ageing in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary angioplasty., Methods and Results: In 1548 consecutive patients with STEMI treated with primary angioplasty, myocardial perfusion was evaluated by myocardial blush grade (MBG) and ST-segment resolution. All clinical and follow-up data were prospectively collected. Advanced age was associated with a significantly higher clinical and angiographic risk profile. We found a linear relationship between increasing age, decreased myocardial perfusion, and higher 1-year mortality. After adjustment for baseline potential confounding variables, increased age was still significantly associated with impaired myocardial blush (MBG 0-1) (P=0.028), and ST-segment resolution (<50%) (P=0.007). At multivariable analysis both age (P<0.0001) and poor myocardial perfusion (P<0.0001) were independent predictors of 1-year mortality., Conclusion: This study shows that impaired reperfusion is an additional determinant of the poor outcome observed with advanced age in patients with STEMI undergoing mechanical revascularization.

Aims: The prognostic role of time-to-treatment in primary angioplasty is still a matter of debate. The aim of our study was to evaluate the relationship between time-to-treatment and myocardial perfusion in patients with ST-segment-elevation myocardial infarction (STEMI) treated by primary angioplasty., Methods and Results: Our study population consisted of 1072 patients with STEMI treated by primary angioplasty from 1997 to 2001. Myocardial perfusion was evaluated by using ST-segment resolution and myocardial blush grade. Time-to-treatment was defined as the time from symptom-onset to the first balloon inflation. Time-to-treatment was significantly associated with the extent of ST-segment resolution, myocardial blush grade, enzymatic infarct size, and 1-year mortality. After adjustment for baseline confounding factors, time-to-treatment was still associated with impaired ST-segment resolution (adjusted OR [95% CI]=1.01 [1.01-1.02], p<0.001) and myocardial blush (adjusted OR [95% CI]=1.01 [1.01-1.02], p<0.0001)., Conclusions: This study shows that in patients with STEMI treated by primary angioplasty prolonged ischaemic time is associated with impaired myocardial perfusion, larger infarct size, and higher 1-year mortality. Therefore, all efforts should be made to shorten ischaemic time as much as possible to achieve better myocardial perfusion and myocardial salvage in primary angioplasty for STEMI.

Aims: To compare long-term, cause-specific mortality after reperfusion therapy for ST segment elevation myocardial infarction (STEMI) in patients with and without diabetes., Methods and Results: Patients with STEMI (n = 395) were randomised to intravenous streptokinase (SK) or primary percutaneous coronary intervention (PCI). Median follow-up was 7.5 years (interquartile range 5.6-8.5). A total of 74 patients (19%) had diabetes. Reduced left ventricular ejection fraction (<40%) after STEMI was more often observed in patients with diabetes (27% vs. 15%, P = 0.02). Patients with diabetes had a higher total mortality compared to patients without diabetes (HR 2.4; P < 0.001). Multivariate analysis confirmed that diabetes was an independent risk factor for long-term mortality (HR 2.3; P < 0.001). The incidence of sudden death was comparable in both patient groups (HR 1.6; P = 0.23). The increased mortality in patients with diabetes was mainly caused by heart failure (HR 3.1; P = 0.004). In patients with diabetes, primary PCI was associated with an improved prognosis., Conclusions: Despite reperfusion therapy, STEMI patients with diabetes have an increased long-term mortality. This is due to death by heart failure and not by an increase in sudden death. Primary PCI is associated with an improved prognosis, particularly in patients with diabetes.

Aim: Although primary angioplasty is effective despite additional transportation delay, improved patency before PCI might be obtained by starting pharmacological pre-treatment before transportation., Methods and Results: From June 2001 to November 2002, 507 patients with acute myocardial infarction, who were transferred to a PCI centre, were randomised to early, pre-hospital initiation of Tirofiban (Early) or to initiation in the catheterisation laboratory (Late). The primary end-point was TIMI flow grade 3 of the infarct-related vessel (IRV) at initial angiography, as assessed by an independent core-lab. The effect of Tirofiban on each TIMI flow component, the presence of thrombus at initial angiography and pre-PCI myocardial blush grade were secondary end-points. A large proportion of patients (41%) was diagnosed and randomised in the ambulance, without intervention of a physician. In the Early group, Tirofiban was administered a median of 59 min (range 11-178 min) earlier than in the Late group. At initial angiography, TIMI 3 flow was present in 19% the Early group and in 15% in the Late group (P = 0.22). The combined incidence of TIMI 2 or 3 flow was present in 43% in the Early group and in 34% in the Late group, respectively (P = 0.04). Thrombus or a fresh occlusion was present in 60% and 73% in the Early and Late group, respectively (P = 0.002). A pre-PCI myocardial blush grades 2 or 3 was more often present in the Early group (30% vs. 22%, P = 0.04). However, no difference in TIMI 3 flow or myocardial blush grade was found between the groups, post-PCI. At one-year follow-up, the combined incidence of death or recurrent MI was not different between the groups (7.0% vs. 7.0%, P = 0.99)., Conclusion: Early initiation of Tirofiban did not improve initial TIMI 3 flow of the IRV significantly. Despite a better patency (TIMI 2 or 3 flow), a lower prevalence of thrombus or fresh occlusion and a better myocardial perfusion in the infarct-related region pre-PCI, no beneficial effect on post-PCI angiographic or clinical outcome was found, as compared to initiation of Tirofiban in the catheterisation laboratory.

Aims: The role of collateral flow in the first hours of infarction remains unclear. Our aim was to determine whether the presence of coronary collateral flow, as evidenced by angiography, has a beneficial effect on infarct size and left ventricular function in acute myocardial infarction (MI) treated by means of early percutaneous coronary intervention (PCI)., Methods: Between 1994 and 2001, 1059 patients with acute MI treated with primary PCI, TIMI (Thrombolysis in Myocardial Infarction) 0 or 1 flow at first contrast injection and technically adequate angiograms for collateral flow detection were analysed., Results: Comparison of collateral flow grades 0, 1, and 2/3 showed that increased collateral flow was associated with a lower incidence of Killip class >/= 2 at presentation (12% vs. 10% vs. 3%, p for trend 0.02), less need for intra-aortic balloon pumping after PCI (17% vs. 13% vs. 5%, p for trend 0.005), better myocardial blush grade (MBG) in infarcts related with the left anterior descending coronary artery (LAD) (MBG3: 14% vs. 18% vs. 34%, p for trend 0.01), and smaller enzymatic infarct size (cumulative lactate dehydrogenase release 36 h after symptom onset [LDHQ(36)]) (1932+/-1531 U/l vs. 1870+/-1458 U/l vs. 1217+/-762 U/l, p for trend 0.041). These beneficial effects were particularly evident in LAD-related infarcts., Conclusion: The presence of angiographically detectable collaterals has a protective effect on enzymatic infarct size and pre- and postintervention haemodynamic conditions in patients with acute MI treated by primary PCI, in particular when Rentrop grade 2/3 is present and the LAD is involved in the infarct.

Background: Only few studies specifically addressed the effect of timing of angiography and/or pre-treatment with a glycoprotein 2b/3a receptor blocker in patients with non-ST elevation acute coronary syndromes (ACS) who undergo invasive treatment., Methods: In a 2-year period, 220 patients with non-ST elevation ACS, were randomized to early angiography without tirofiban pre-treatment (Early strategy) or to delayed angiography after 24-48h pre-treatment with tirofiban (Late strategy). The first 48h after admission, CKmb levels were measured and enzymatic infarct size (LDHQ(48)) was assessed by the area under the LDH release curve. When PCI was performed beyond 48h, CKmb was measured 6 and 12h afterwards., Results: Median time to angiography was 6 (Early) and 50 (Late) hours. PCI was performed in 130 patients (59%). In these patients, a patent (TIMI 2 or 3 flow) culprit vessel was more often present in the Late group compared to the Early group (66% vs 82% p=0.05). In patients with an elevated CKmb (n=96, 44%), LDHQ(48)was significantly lower in patients who underwent angiography after pre-treatment with tirofiban (629+/-503U/L (Early) vs 432+/-441U/L (Late), p=0.02). No difference in clinical outcome between the groups was observed at 30 days follow-up., Conclusion: This pilot study showed that a strategy of delayed angiography with concomitant pre-treatment with tirofiban is associated with improved angiographic outcomes and less initial enzyme release, compared to a strategy of immediate angiography without 2b/3a inhibitor pre-treatment. The use of an end point parameter, which assess total enzyme release over a given period of time, might be of special value in patients with non-ST elevation ACS, who undergo very early invasive treatment.

Aims: Although recognized as an important feature of atherosclerotic coronary disease, little is known about the frequency and prognostic importance of distal embolization during primary angioplasty for acute myocardial infarction., Methods and Results: As part of a randomized trial of thrombolysis vs primary angioplasty, 178 patients with acute myocardial infarction were treated with primary angioplasty. In these patients the occurrence of distal embolization after angioplasty was assessed. Embolization was defined as a distal filling defect with an abrupt 'cutoff' in one of the peripheral coronary artery branches of the infarct-related vessel, distal to the site of angioplasty. We analysed myocardial blush grade, ST-T segment elevation resolution, enzymatic infarct size and left ventricular ejection fraction in patients with and without distal embolization. Clinical information was collected for a mean of 5 years. Distal embolization was present in 27 patients (15.2%). Mean age and gender were not different from patients without distal embolization. Angiographic success (thrombolyis in myocardial infarction flow grade 3 and residual stenosis <50%) after primary angioplasty was less frequently observed in patients with distal embolization (70% vs 90%, P<0.01). Myocardial blush and ST-T segment elevation resolution after angioplasty were reduced when distal embolization was present. Patients with distal embolization had a larger enzymatic infarct size (mean cumulative lactate dehydrogenase measured over 72 h, 1612 vs 847, P<0.05) and a lower left ventricle ejection fraction at discharge (42% vs 51%, P<0.01). Long-term mortality was higher in patients with distal embolization (44% vs 9%, P<0.001)., Conclusion: Distal embolization in patients treated with primary angioplasty is visible on the coronary angiogram in 15.2% of patients. It is related to reduced myocardial reperfusion, more extensive myocardial damage and a poor prognosis. Additional pharmacological interventions and/ or mechanical devices should be studied to prevent and/or treat distal embolization., (Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Aims: To investigate changes in left ventricular function in the first 6 months after acute myocardial infarction treated with primary angioplasty. To assess clinical variables, associated with recovery of left ventricular function after acute myocardial infarction., Methods: Changes in left ventricular function were studied in 600 consecutive patients with acute myocardial infarction, all treated with primary angioplasty. Left ventricular ejection fraction was measured by radionuclide ventriculography in survivors at day 4 and after 6 months. Patients with a recurrent myocardial infarction within the 6 months were excluded., Results: Successful reperfusion (TIMI 3 flow) by primary angioplasty was achieved in 89% of patients. The mean ejection fraction at discharge was 43.7%+/-11.4, whereas the mean ejection fraction after 6 months was 46.3%+/-11.5 (P<0.01). During the 6 months, the mean relative improvement in left ventricular ejection fraction was 6%. An improvement in left ventricular function was observed in 48% of the patients; 25% of the patients had a decrease, whereas in the remaining patients there was no change. After univariate and multivariate analysis, an anterior infarction location, an ejection fraction at discharge < or =40% and single-vessel disease were significant predictors of left ventricular improvement during the 6 months., Conclusions: After acute myocardial infarction treated with primary angioplasty there was a significant recovery of left ventricular function during the first 6 months after the infarction. An anterior myocardial infarction, single-vessel coronary artery disease, and an initially depressed left ventricular function were independently associated with recovery of left ventricular function. Multivessel disease was associated with absence of functional recovery. Additional studies, investigating complete revascularization are needed, as this approach may potentially improve long-term left ventricular function., (Copyright 2001 The European Society of Cardiology.)

Aims: Intra-aortic balloon pumping reduces afterload and may be effective in improving reperfusion in high risk infarct patients treated with primary angioplasty., Methods: High risk infarct patients referred from other centres for primary PTCA were randomized to treatment with or without an intra-aortic balloon pump. The primary end-point consisted of the combination of death, non-fatal reinfarction, stroke or an ejection fraction <30% at the 6 month follow-up. A weighted unsatisfactory outcome score (as previously described by Braunwald), enzymatic infarct size and left ventricular ejection fraction were secondary end-points., Results: During a 3.5 year period, 238 patients were randomized, 118 to intra-aortic balloon pump therapy and 120 to no intra-aortic balloon pump therapy. Cross-over (25% in the intra-aortic balloon pump group and 31% in the no-intra-aortic balloon pump group) occurred in both treatment arms. The primary end-point was reached in 31 (26%) patients assigned to an intra-aortic balloon pump and in 31 (26%) assigned to no intra-aortic balloon pump (P=0.94). Enzymatic infarct size (LDHQ72) was calculated in 163 (68%) patients and was not significantly different between either group (intra-aortic balloon pump: 1616+/-1148, no intra-aortic balloon pump: 1608+/-1163). The left ventricular ejection fraction was measured at the 6 month follow-up in 168 patients (80% of patients alive). No difference in ejection fraction was found in either group (intra-aortic balloon pump: 42+/-13%, no intra-aortic balloon pump: 40+/-14%, P=0.51). Major complications occurred in 8% of patients treated with an intra-aortic balloon pump., Conclusions: Systematic use of intra-aortic balloon pumping after primary angioplasty does not lead to myocardial salvage or to a better clinical outcome in high-risk infarct patients. Use of intra-aortic balloon pumping after primary PTCA for acute myocardial infarction should be reserved for patients with severe haemodynamic compromise., (Copyright 1999 The European Society of Cardiology.)

Background: Reperfusion therapy by primary coronary angioplasty has been shown to be beneficial for patients who present themselves up to 12 h after the onset of symptoms. However, the relationship between outcome and ischaemic time for patients who present relatively late after the onset of symptoms is still uncertain. The aim of this study was to investigate differences in patient characteristics, left ventricular function and clinical outcome among early (< 3 h), intermediate (3-6 h) and late (6-24 h) treated patients., Methods and Results: From August 1990 until December 1995, we studied 496 patients who underwent primary coronary angioplasty for acute myocardial infarction. Patients who underwent reperfusion therapy between 6 and 24 h were more often of female gender and more often had diabetes. Primary coronary angioplasty was less successful with later time to reperfusion. Patients who had reperfusion therapy within 6 h showed recovery of left ventricular function at 6 months follow-up, while the left ventricular function of patients treated late had deteriorated. Reocclusion of the infarct-related vessel at follow-up coronary angiography was highest for patients with an ischaemic time of more than 6 h. They more often suffered a repeat myocardial infarction and had a significantly higher 6 months mortality. After adjustment for age, heart rate at presentation, gender, and the presence of diabetes by multi-variate analysis, ischaemic time remained an independent predictor of both left ventricular function recovery and 6 month mortality., Conclusions: The time from symptom onset to reperfusion is related to some baseline clinical characteristics, procedural success rate, left ventricular function and clinical outcome.

The comparative efficacy of thrombolytic drugs and primary angioplasty for acute myocardial infarction have recently been studied, but long-term follow-up data have not yet been reported. We conducted a randomized trial involving 301 patients with acute myocardial infarction; 152 patients were randomized to primary angioplasty and 149 to intravenous streptokinase. Left ventricular function was assessed with a radionuclide technique both at hospital discharge and at the end of the follow-up period. Follow-up data were collected after a mean (+/-SD) of 31 +/- 9 months. Total medical costs were calculated. At the end of the follow-up period, 5% of the angioplasty patients had died from a cardiac cause compared to 11% of the patients randomized to intravenous streptokinase, P = 0.031. Cardiac death or a non-fatal reinfarction occurred in 7% of angioplasty patients compared to 28% of streptokinase patients, P < 0.001. There was a sustained benefit of angioplasty compared to streptokinase on left ventricular function. The total medical costs in the two groups were similar. Coronary anatomy (patency and single or multivessel disease), infarct location and previous myocardial infarction were important determinants of clinical outcome and costs. After 31 +/- 9 months of follow-up, primary angioplasty compared to intravenous streptokinase results in a lower rate of cardiac death and reinfarction, a better left ventricular ejection fraction, and no increase in total medical costs.

Background: The purpose of this study was to evaluate catheterization laboratory events and angiographic findings in patients randomly assigned to undergo primary coronary angioplasty or to receive intravenous streptokinase for acute myocardial infarction., Methods: We analysed angiographic data in 301 patients with acute myocardial infarction, randomly assigned to undergo primary coronary angioplasty without antecedent thrombolytic therapy or to receive intravenous streptokinase therapy. Follow-up coronary angiography was preferably performed after 3 months. All angiograms were analysed with a quantitative coronary analysis system., Results: Of the 152 patients assigned to angioplasty treatment, 140 underwent this procedure with a success rate of 97%. The residual diameter stenosis of the infarct-related vessel immediately after angioplasty was 27 +/- 15% and there were major events in 14% of the patients in the catheterization laboratory. At follow-up angiography after a mean interval of 92 days in the angioplasty assigned patients, a diameter stenosis of 35 +/- 22% was observed in this group. The restenosis rate was 28% and the reocclusion rate 5%. A Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow immediately after angioplasty was predictive for reocclusion at follow-up (P = 0.001). In the streptokinase assigned patients (149) the infarct-related vessel was patent at follow-up angiography after a mean of 22 days in 66% of the patients with a mean residual diameter stenosis of 77 +/- 20%., Conclusion: Primary coronary angioplasty is a highly effective and safe reperfusion modality for patients with acute myocardial infarction. However, TIMI grade 2 flow through the infarct-related vessel immediately after angioplasty is a predictor of reocclusion.