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Background: The extent of ST-segment resolution in the 12-lead electrocardiograph (ECG) obtained early after reperfusion therapy in patients with ST-elevation myocardial infarction (MI) has been shown to predict short- and long-term mortalities. To improve the ease of this method in clinical practice, we sought to evaluate the optimal cutoffs and the prognostic value of ST resolution (STR) measured in a single ECG lead., Methods: In conjunction with the Intravenous nPA for the Treatment of Infarcting Myocardium Early (InTIME)-2 study, in which patients with an ST-elevation MI of <6 hours' duration were treated with alteplase or lanoteplase, 12-lead ECGs were obtained at baseline and 90 minutes after the start of fibrinolytic therapy in 3030 patients., Results: There was a close correlation between the extent of the sum STR and single-lead ST-elevation resolution ( r = 0.94). The optimal cutoffs for definition of single-lead complete, partial, and no-STR groups were 70% and 50% for anterior infarcts and 70% and 20% for inferior infarcts. The cardiac 30-day mortality rates for the 2 sets of risk groups by sum or single-lead STR were as follows: no resolution, 9.5% vs 10.3%; partial resolution, 5.0% vs 3.6%; complete resolution, 2.0% vs 1.2%. The predictive power was significantly better for single-lead STR., Conclusions: ST resolution obtained in a single lead is an easy and accurate prognosticator of cardiac 30-day mortality in patients with ST-elevation MI. It is therefore useful for early identification of low- and high-risk subgroups after fibrinolysis and as a surrogate end point in clinical trials.

Aims Acute myocardial infarction complicated by cardiogenic shock is associated with an exceedingly high mortality, even if patients are treated with early reperfusion therapy. The aim of this study was to evaluate predictors of in-hospital mortality of a large cohort of consecutive patients with cardiogenic shock treated with primary percutaneous coronary intervention (PCI). Methods and results Between July 1994 and March 2001 all interventions performed in 80 centres in Germany were prospectively entered into the primary PCI registry of the ALKK. A total of 9422 procedures were registered, of these 1333 (14.2%) were performed in patients with cardiogenic shock. Total in-hospital mortality was 46.1% and was dependent on TIMI flow grade after PCI, with mortality rates of 78.2%, 66.1% and 37.4% in patients with TIMI 0/1, TIMI 2 and TIMI 3 flow, respectively. In a multivariate analysis left main disease, TIMI <3 flow after PCI, older age, three-vessel disease and longer time-intervals between symptom onset and PCI were significant independent predictors of mortality. The relative number of PCIs performed in patients with cardiogenic shock did not change significantly from 1995-2000. There was a significant decrease in mortality over the years (P for trend 0.02). Conclusions In-hospital mortality in patients with acute myocardial infarction complicated by cardiogenic shock remains high, even with early interventional therapy. However, our data demonstrate that the PCI in these high-risk patients is feasible in a wide spectrum of community hospitals with acceptable success rates. Our results seen in connection with the results of the randomized SHOCK study advocate an early invasive approach in younger patients with cardiogenic shock, while the best strategy in elderly patients is still a matter of debate.

Background: Successful early reperfusion of the infarcted myocardium as indicated by complete resolution of ST-segment elevations has been shown to be associated with an improved outcome in patients with acute ST-elevation myocardial infarction (AMI). The aim of this study was to compare early ST resolution in patients treated with primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for AMI., Methods: A total of 1379 patients with AMI whose symptoms began <6 hours previously were enrolled in the Evaluation of the Safety and Cardioprotective effects of eniporide in Acute Myocardial Infarction (ESCAMI) trial and treated with primary PTCA (n = 528) or thrombolytic therapy (n = 851). Twelve-lead electrocardiograms (ECG) were obtained at baseline, directly after PTCA and at 90 minutes after the initiation of thrombolytic therapy., Results: There were no differences with respect to clinical or ECG baseline variables between the 2 groups. The time intervals between hospital admission and ECG 2 (obtained 0-30 min after PTCA and 90 min after start of thrombolysis) were 121 +/- 62 minutes in the PTCA group and 137 +/- 57 minutes in the thrombolysis group, respectively. In ECG 2, complete (> or =70%) ST resolution was observed more often in the PTCA treated patients (35 vs 27%, P =.003). The incidence of congestive heart failure until 6 weeks was lower in the PTCA group (11.2% vs 17.6, P =.001). Mortality after 6 weeks (3.4% vs 5.6%, P =.07) and after 6 months (4.5% vs 7.1%, P =.06) tended to be lower in the PTCA group., Conclusion: Primary PTCA compared to thrombolytic therapy is associated with an accelerated myocardial reperfusion within 90 minutes after the start of reperfusion therapy. This early advantage in myocardial reperfusion is associated with an improved clinical outcome.

Background: Percutaneous transluminal coronary angioplasty of the infarct-related artery in stable survivors of acute myocardial infarction is often performed, even in patients without any symptoms or residual ischemia. Despite the lack of randomized studies, it is widely believed that this intervention will improve the clinical outcome of these patients., Methods and Results: Three hundred patients with single vessel disease of the infarct vessel and no or minor angina pectoris in the subacute phase (1 to 6 weeks) after an acute myocardial infarction were randomized to angioplasty (n=149) or medical therapy (n=151). Primary end point was the survival free of reinfarction, (re)intervention, coronary artery bypass surgery, or readmission for severe angina pectoris at 1 year. The event-free survival at 1 year was 82% in the medical group and 90% in the angioplasty group (P=0.06). This difference was mainly driven by the difference in the need for (re)interventions (20 versus 8, P=0.03). At long-term follow-up (mean, 56 months), survival was 89% and 96% (P=0.02). Survival free of reinfarction, (re)intervention, or coronary artery bypass surgery was 66% and 80% in the medically and interventionally treated patients, respectively (P=0.05). The use of nitrates was significantly lower in the angioplasty group, both at 1 year (38% versus 67%, P=0.001) and at long-term follow-up (36% versus 55%, P=0.006)., Conclusions: Percutaneous revascularization of the infarct-related coronary artery in stable patients with single vessel disease improves clinical outcome at long-term follow-up and reduces the use of nitrates. The results of our study should be reproduced in a confirmatory study with a larger sample size before percutaneous coronary intervention in this low-risk patient subgroup, after myocardial infarction can be recommended as routine treatment in clinical practice.

Objective: Patients with acute myocardial infarction complicated by cardiogenic shock have a high mortality despite the use of early reperfusion therapies with thrombolysis or percutaneous coronary intervention (PCI). Therefore, there is still need to evaluate therapy strategies in these patients., Design: The REO-SHOCK trial was a prospective, non-randomized study, aimed at evaluation of a routine strategy of early abciximab and PCI in a high-risk group of acute ST elevation myocardial infarction (STEMI) patients with cardiogenic shock., Results: Patients (n = 40) planned for coronary angioplasty or stenting received abciximab (0.25 mg/kg bolus followed by 0.125 mg/kg/minute over 12 hours), heparin and aspirin. The intervention was successful in 92.5% of the patients and achieved Thrombolysis In Myocardial Infarction (TIMI) grade 3 patency in 32 patients (80%). The primary endpoint, total mortality after 30 days, was observed in 42.5% (17/40), and was significantly different between patients aged > 75 years and patients aged 75 years (91% versus 24%, respectively; p < 0.001). Major bleeding occurred in 2 patients (5%), but stroke occurred in none., Conclusion: A strategy of abciximab with primary PCI in high-risk patients with cardiogenic shock is safe, associated with a high procedural success rate and seems to improve outcomes in patients < 75 years old.

Background: Infection with Chlamydia pneumoniae is suspected to contribute to the pathogenesis of human atherosclerosis. We investigated whether treatment with the macrolide antibiotic roxithromycin would reduce mortality or morbidity in patients with an acute myocardial infarction., Methods and Results: Eight hundred seventy-two patients with an acute myocardial infarction (AMI) were randomly assigned to receive double-blind treatment with either 300 mg roxithromycin or placebo daily for 6 weeks. Primary end point was total mortality during 12-month follow-up. Four hundred thirty-three patients were treated with roxithromycin and 439 with placebo. With the exception of a higher proportion of patients suffering an anterior wall AMI (48.1% in the roxithromycin group versus 40.2% in the placebo group; P=0.027) and a lower prevalence of chronic obstructive pulmonary disease in the roxithromycin group (3.5% versus 6.9%, P=0.028), baseline characteristics, reperfusion therapy, and medical treatment were well balanced between the two groups. More patients in the roxithromycin group interrupted their study medication before completion of at least 4 weeks of treatment (78 of 433 [18%] versus 48 of 439 [11%]; P=0.003; odds ratio, 1.8; 95% CI, 1.2 to 2.6). Follow-up at 12 months was achieved in 868 of 872 (99.5%) patients. Total mortality at 12 months was 6.5% (28 of 431) in the roxithromycin group compared with 6.0% (26 of 437) in the placebo group (odds ratio, 1.1; 95% CI, 0.6 to 1.9; P=0.739). There were also no differences in the secondary combined end points at 12 months., Conclusions: Treatment of AMI patients with roxithromycin did not reduce event rates during 12 months of follow-up. Therefore, our findings do not support the routine use of antibiotic treatment with a macrolide in patients with AMI.

Objectives: This study was designed to test the hypothesis that eptifibatide and reduced-dose tissue plasminogen activator (t-PA) will enhance infarct artery patency at 60 min in patients with acute myocardial infarction (AMI)., Background: Combination fibrin and platelet lysis improves epicardial and myocardial reperfusion in AMI., Methods: Patients were enrolled in a dose finding (Phase A, n = 344) followed by a dose confirmation (Phase B, n = 305) protocol. All patients received aspirin and weight-adjusted heparin and underwent angiography at 60 and 90 min. In Phase A, eptifibatide in a single or double bolus (30 min apart) of 180, 180/90 or 180/180 microg/kg followed by an infusion of 1.33 or 2.0 microg/kg per min was sequentially added to 25 or 50 mg of t-PA. In Phase B, patients were randomized to: 1) double-bolus eptifibatide 180/90 (30 min apart) and 1.33 microg/kg per min infusion with 50 mg t-PA (Group I); 2) 180/90 (10 min apart) and 2.0 g/kg per min with 50 mg t-PA (Group II); or 3) full-dose, weight-adjusted t-PA (Group III)., Results: In Phase A, the best rate of Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved using 180/90/1.33 microg/kg per min eptifibatide with 50 mg t-PA: 65% and 78% at 60 and 90 min, respectively. In Phase B, the incidence of TIMI flow grade 3 at 60 min was 42%, 56% and 40%, for Groups I through III, respectively (p = 0.04, Group II vs. Group III). The median corrected TIMI frame count was 38, 33 and 50, respectively (p = 0.02). TIMI major bleeding was reported in 8%, 11% and 6%, respectively; intracranial hemorrhage occurred in 1%, 3% and 2% of patients (p > 0.5 for both). The incidences of death (4%, 5% and 7%), reinfarction or revascularization at 30 days were similar among the three treatment groups., Conclusions: In comparison with standard t-PA regimen, double-bolus eptifibatide (10 min apart) with a 48-h infusion and half-dose t-PA (Group II) is associated with improved quality and speed of reperfusion. The safety profile of this therapy is similar to that of other combination regimens.

Objectives: We conducted an international, prospective, randomized, double-blind, placebo-controlled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarction (MI) to investigate the effect of eniporide on infarct size and clinical outcome., Background: Experimental studies suggest that the activity of the Na(+)/H(+) exchange (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform and has been shown to limit infarct size in experimental models., Methods: The primary efficacy end point was the infarct size measured by the cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha-HDBH) (area under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eniporide given as a 10-min infusion before start of reperfusion therapy were compared with placebo in 430 patients, and in stage 2, 100 and 150 mg eniporide were compared with placebo in 959 patients., Results: In stage 1, the administration of 100 mg and 150 mg eniporide resulted in smaller infarct sizes (mean alpha-HBDH AUC in U/ml x h, placebo: 44.2, 100 mg eniporide: 40.2, 150 mg eniporide: 33.9), especially in the angioplasty group. In contrast, in stage 2 there was no difference in the enzymatic infarct size between the three groups (placebo: 41.2, 100 mg eniporide: 43.0, 150 mg eniporide: 41.5). Overall there was no effect of eniporide on clinical outcome (death, cardiogenic shock, heart failure, life-threatening arrhythmias). However, there was a significant reduction of the incidence of heart failure in patients reperfused late (>4 h)., Conclusions: In this large study administration of the NHE-1 inhibitor eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.

Unlabelled: In evolving myocardial infarction the extent of ST segment deviation reflects the existing ischemic myocardial injury and thus conveys very useful early prognostic information. In recent years, the sum of ST segment elevation resolution (sum STR) has been proven to be an excellent early prognostic indicator. However, the predictive power of sum STR has never been systematically compared with that of other methods of evaluation of ST segment deviation recovery. We, therefore, proposed to compare the prognostic power of ST segment changes evaluated by either sum STR or by ST segment resolution in only the one lead showing the maximal deviation (lead STR) or only by the existing ST segment deviation in the single ECG lead of maximum ST deviation present at a given time point after thrombolysis (lead STE)., Methods and Results: In conjunction with the Intravenous nPA for Treatment of Infarcting Myocardium Early (InTIME) II Study, which compared mortality in patients with acute myocardial infarction randomized within 6 hours of symptom onset to receive either Lanoteplase or Alteplase, all 3593 German and Polish patients participated in an ST segment resolution substudy. A 12-lead ECG was recorded at baseline and at 90 and at 180 minutes after start of thrombolytic therapy. The areas under the receiver-operating characteristic (ROC) curves to compare the power to predict 30 day cardiac mortality for sum STR, lead STR, and lead STE were at 90 min 0.686, 0.714, and 0.761 (p < 0.002), and at 180 min 0.678, 0.703, and 0.755 (p < 0.001), respectively. In multivariate analysis lead STE was an independent predictor of outcome even when adjustment was made for sum STR, lead STR, and clinical variables. Cardiac mortality rates at 30 days for lead STE risk groups, classified as low, medium, or high (percent of patients in brackets), were at 90 min 1.0% (43%), 4.0% (32%), and 12.8% (25%), and at 180 min 1.5% (55%), 3.8% (31%), and 15.2% (14%), respectively., Conclusions: Simple measurement of the ST segment deviation existing in the one ECG lead with the greatest deviation on the ECG recorded 90 or 180 minutes after thrombolysis enables the identification of the major subsets of patients who are either at very low or exceptionally high risk of mortality.

Aims The purpose of this study was to validate ST segment resolution as a non-invasive marker for patency of the infarct-related artery 90 min after the start of streptokinase therapy in patients with acute myocardial infarction. Methods and Results In the HIT-4 angiographic substudy, 447 patients with acute myocardial infarction or =70% ST resolution (n=70) had a 92% probability of TIMI 2/3 flow, while <30% ST resolution (n=172) was associated with the absence of TIMI 3 flow in 84% of patients. Conclusions Despite fairly good sensitivities and specificities the prediction of infarct vessel patency by ST resolution in the individual patient is limited. However, patients with > or =70% ST resolution are likely to have a patent infarct artery and <30% ST resolution predicts epicardial vessel occlusion or, since persistent ST elevation reflects the existing ischaemic myocardial injury, absence of myocardial perfusion., (Copyright 2001 The European Society of Cardiology.)

Aims: Oral glycoprotein IIb/IIIa inhibitors might enhance the early benefit of an intravenous agent and prevent subsequent cardiac events in patients with acute coronary syndromes. We assessed the safety and preliminary efficacy of 1 month treatment with three dose levels of the oral GP IIb/IIIa blocker lefradafiban in patients with unstable angina or myocardial infarction without persistent ST elevation., Methods: The Fibrinogen Receptor Occupancy STudy (FROST) was designed as a dose-escalation trial with 20, 30 and 45 mg lefradafiban t.i.d. or placebo. Five hundred and thirty-one patients were randomized in a 3:1 ratio to lefradafiban or placebo in a double-blind manner. Efficacy was assessed by the incidence of death, myocardial infarction, coronary revascularization and recurrent angina. Safety was evaluated by the occurrence of bleeding classified according to the TIMI criteria and by measuring clinical laboratory parameters., Results: There was a trend towards a reduction in cardiac events with lefradafiban 30 mg when compared with placebo and lefradafiban 20 mg. The benefit was particularly apparent in patients with a positive (> or = O.1 ng. ml(-1)) troponin I test at baseline and less so in those with a negative test result. In patients receiving lefradafiban, the cardiac event rate decreased with increasing minimal levels of fibrinogen receptor occupancy. There was a dose-dependent increase in the incidence of bleeding: the composite of major or minor bleeding occurred in 1% of placebo patients, 5% of patients receiving lefradafiban 20 mg and in 7% of patients receiving 30 mg, with an excessive risk (15%) in the 45 mg group which resulted in early discontinuation of this dose level. Gingival and arterial or venous puncture site bleedings were most common and accounted for more than 60% of all haemorrhagic events. There was an increased incidence of neutropenia (neutrophils <1. 5 x 10(9)/l) in the lefradafiban groups (5.2% vs 1.5% in the placebo group), which did not result from bone marrow depression but rather from a reversible redistribution of neutrophils by margination or clustering., Conclusion: One month's treatment with the oral glycoprotein IIb/IIIa inhibitor lefradafiban in patients with unstable angina and myocardial infarction without persistent ST elevation resulted in a decrease in cardiac events with lefradafiban 30 mg and a dose-dependent increase in haemorrhagic events. The observed favourable trend towards a reduction in cardiac events in patients with elevated troponin levels requires confirmation in a large clinical trial., (Copyright 2000 The European Society of Cardiology.)

Aims: Thrombolytic therapy restores coronary patency in patients with acute myocardial infarction, although normal perfusion (TIMI 3 flow) is not achieved in all patients. In an attempt to improve TIMI 3 flow, a combination of full-dose streptokinase, aspirin and escalating dosages of a platelet glycoprotein IIb/IIIa receptor blocker, eptifibatide, vs placebo were tested., Methods and Results: A bolus of 180 microg. kg(-1)of eptifibatide was administered in each group, followed by a 72 h continuous infusion of 0.75 (44 patients), 1.33 (n=45) and 2.00 microg. kg(-1). min(-1)(n = 30); 62 patients received placebo. Normal perfusion (TIMI 3 flow) at 90 min was observed in 31% of placebo patients compared to 46, 42 and 45% in the ascending eptifibatide groups (44% for combined eptifibatide groups, P = 0.07). Patency (TIMI 2 and 3 flow combined) increased from 61% (placebo) to 78% for the combined eptifibatide groups (P = 0.02). Reocclusion was infrequent. No differences were observed in TIMI flow grades among eptifibatide groups. Major and minor bleeding was increased and occurred mainly at the arterial puncture site., Conclusion: A combination of full dose streptokinase with different eptifibatide regimens enhanced coronary perfusion, but bleeding risk was excessive. Additional trials are needed with different dosage regimens to determine the optimal combination of fibrinolytic agents and platelet glycoprotein IIb/IIIa receptor blockers., (Copyright 2000 The European Society of Cardiology.)

In cases with protected left main stenosis by previous bypass surgery or as an emergency intervention in patients presenting with acute myocardial infarction and cardiogenic shock, percutaneous transluminal coronary angioplasty is performed as an alternative treatment strategy to bypass surgery. A review of 262 left main angioplasties revealed a procedure-related mortality in cases without protection of the left main coronary artery of 9.1% (4/44), in cases with partially protected left main stenosis by collaterals to either left coronary artery of 4.8% (1/21) and 0.5% (1/187) in cases with nonobstructed bypass grafts to either left coronary artery. Coronary angioplasty of an unprotected left main coronary artery, had an unacceptably high procedure-related mortality rate and should therefore not be performed even in cases of emergency intervention. The risk stratification of the procedure can be evaluated by the proposed grading of left main artery protection.

Context: Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored., Objective: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure., Design: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year., Setting: Three hundred thirteen sites in 14 countries., Participants: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy., Interventions: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001)., Main Outcome Measures: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients., Results: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively)., Conclusions: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.

Background: Mortality from cardiac surgery is an essential indicator of quality and forms the basis of treatment strategy decisions in eligible patients. No contemporary complete data on unselected adult cardiac surgery patients are available in Germany., Methods and Results: A registry was started in June 1997 of all patients referred to surgery from 85 cardiology centres in Germany. The registry was intended to include 10 000 patients and this number was reached in March 1998. Follow-up of the patients was by simple questionnaire, reporting the date of surgery, major complications, and symptomatic improvement. If the questionnaire was not returned, a reminder letter was sent and, if necessary, further telephone investigations were performed. This resulted in 99.9% complete data. Of 10 525 patients operated on, 3.91% had died by 30 days after surgery. The overall operative mortality was 4.57%, which included 69 patients who died after more than 30 days from complications related to surgery. By multivariate analysis, the following predictors of mortality were identified: previous surgery, emergency or complex operation; age >75 years, female gender, cardiac failure, angina CCS class IV, and three-vessel coronary disease. An integral part of the registry was a pre-operative prediction of surgical risk in five categories. This risk estimate revealed a surprisingly correct prediction of the mortality observed., Conclusions: In a representative unselected group of cardiac surgery patients, operative mortality was 4.57%. Several procedural and clinical parameters were significantly correlated with mortality, but the risk increment by each of these factors was small. Unstructured clinical judgement reliably predicted the operative risk.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality in the developed countries. Thrombotic occlusion of a coronary artery has been shown to cause acute myocardial infarction in over 90% of the cases. Early and complete restoration of bloodflow in the infarct-related coronary artery is the principal mechanism by which reperfusion therapy improves outcomes in patients with acute myocardial infarction. Thrombolytic therapy has been shown to reduce mortality when given early after symptom onset. However, even the most effective, approved thrombolytic regimens achieve normal (so-called TIMI 3) flow in the infarct vessel at 60-90 minutes only in about half of the patients and reocclusion occurs in 5-10%. Bleeding events, especially intracranial bleedings, observed in up to 1% of the patients, are the most severe complication of thrombolysis. Primary percutaneous transluminal coronary angioplasty (PTCA) is associated with somewhat higher patency rates and significantly fewer strokes than thrombolysis, but confers a reocclusion rate of about 5-10% and it is not universally available. While smaller randomized studies suggested a significant advantage of PTCA over thrombolysis, these results could not be confirmed in the larger GUSTO IIb angioplasty study in over 1000 patients and in non-randomized comparisons in large registries. Therefore, a general mortality advantage of PTCA over thrombolysis could not be demonstrated. Primary PTCA should be preferred in patients with contraindications against thrombolysis, patients with a high risk for intracranial bleedings (age > 75 and high blood pressure on admission) and hemodynamically unstable patients. There are several approaches to improve outcome of patients with acute myocardial infarction: new fibrinolytic agents may improve early infarct related patency, single bolus administration of thrombolytics may reduce time-to-treatment, stent implantation may improve direct PTCA, enhanced thrombin and platelet inhibition may facilitate both, thrombolysis and primary PTCA, enhance reperfusion on the cellular level and reduce reocclusions and ultimately improve prognosis of patients with acute myocardial infarction.

Aims: Previous studies revealed that >/=70% or <30% ST segment elevation resolution 180 min after the start of thrombolysis is a strong predictor of either favourable or poor outcome. The aim of this study was to compare the prognostic value of ST segment elevation resolution at 90 and 180 min after the start of streptokinase infusion., Methods and Results: The Hirudin for Improvement of Thrombolysis (HIT)-4 study of 1208 patients compared streptokinase therapy in conjunction with either r-hirudin or heparin. Complete ST segment elevation resolution (>/=70%) at 90 and 180 min identified 25% and 50%, respectively, of all patients with a 30 day cardiac mortality of less than 2%. Forty-four percent of patients had no ST segment elevation resolution (<30%) at 90 min and the 30 day cardiac mortality was 7.3%. At 180 min, the no ST segment elevation resolution group decreased to 15% of all patients while the mortality risk increased to 13.6%., Conclusions: ST segment elevation resolution is a useful tool for early risk stratification and the strategy of rescue angioplasty. Complete ST segment elevation resolution within 180 min of the start of streptokinase therapy indicates excellent survival prospects in 50% of patients. A half of these low risk patients can be identified at 90 min. A high risk group appears to be best characterized by no ST segment elevation resolution at 180 min rather than at 90 min.

Despite advances in therapy acute myocardial infarction is associated with a mortality rate of up to 30%. Early and complete reperfusion of the infarct related artery (defined as TIMI flow 3 at 90 minutes following therapy) as obtained with thrombolytic therapy in 50 to 80% of patients improves survival and enhances ventricular function. Failure to achieve recanalization should prompt further intervention (second attempt of thrombolysis or rescue-PTCA). Various cardiac markers known from diagnosing acute myocardial infarction or risk stratification in unstable angina pectoris have been assessed in their ability to predict successful reperfusion/failure of therapy. Following reperfusion creatinkinase (CK) and its isoform CK-MB, troponin and myoglobin show an early and rapid rise to a high maximum value with rapid normalization. For creatinkinase time to peak values of less than 9 hours or rates of increase of > 50 U/h (> or = 10 U/h for CK-MB activity) within the first 2.5 hours following thrombolysis have been suggested as useful indicators of successful reperfusion. The same applies for a troponin (T)slope > 0.5 ng/ml/h within the first hour (Table 5). The major limitation in applying either creatinkinase, troponin or even lactatdehydrogenase (LDH) is their comparatively late release (4 to 6 hours) following myocardial infarction. In that respect myoglobin (though not specific for cardiac injury) seems ideal for guidance of intervention after failed thrombolysis. The I.S.A.M. study included 1,741 patients with acute myocardial infarction of less than 6 hours duration being given either streptokinase or placebo. Serial blood samples for measurement of cardiac enzymes were drawn within the first 50 hours. In the streptokinase group the time to peak concentration of CK-MB activity was significantly lower (mean 10.9 hours vs 16.1 hours following initiation of treatment) as was the area under the CK-MB curve indicating reduction of infarct size (Table 2). A substudy investigating the myoglobin release in 120 patients having received streptokinase or placebo demonstrated higher maximum values in the streptokinase group (mean 3008 vs 2097 ng/ml), a shorter time to peak interval following treatment (3.4 vs 6.5 hours) and a reduction in infarct size as suggested by a smaller area under the myoglobin curve (17,377 vs 23,240 ng/ml x h) (Table 3). For LDH/alpha-HBDH the reduction in time to peak intervals was less impressive (Table 4). In angiographic studies with TIMI flow 3 at 90 minutes in the infarct related artery in 22 patients (Figure 5) the maximum myoglobin value was reached in less than 4.2 hours (mean value plus SEM) following treatment (9.5 hours for CK-MB activity). Therefore, myoglobin seems to be the preferred marker in reperfusion assessment.