Augmented platelet aggregation as predictor of reocclusion after thrombolysis in acute myocardial infarction

RATIONALE: Reocclusion after thrombolysis diminishes the benefits of early reperfusion after acute myocardial infarction (AMI). No clinical or laboratory variables have been identified as predictors for reocclusion yet. METHODS AND RESULTS: To evaluate hemostatic variables as potential risk determinants platelet aggregation (PA, representing platelet activity), thrombin/antithrombin complexes (TAT, representing thrombin generation), and plasminogen activator inhibitor type 1 (PAI-1, representing endogenous fibrinolysis) were determined in 31 patients with AMI at 0, 1, 2. and 12 h after the start of thrombolysis as well as at hospital discharge. Reocclusion (defined as reinfarction or angiographically confirmed, clinically silent coronary reocclusion) occurred in 5 patients within 5-14 days and in 8 patients within 1 year. TAT plasma concentrations were lower in patients with reocclusion than in those without (9.9+/-5.7 vs. 22.9+/-22.2 ng/ml at 2 h, 6.5+/-3.1 vs. 1 1.2+/-6.4 ng/ml at 12 h, means+/-SD, p <0.05 each). Neither concentration nor activity of PAI-1 in plasma differed between both patient groups. However, both slope and maximum of PA (induced by 2 micromol/l ADP) were augmented in patients with reocclusion (slope: 39.4+/-1.7 vs. 32.5+/-7.4 at 2 h, p <0.001; 42.6+/-2.6 vs. 36.6+/-8.9 at 12 h, p <0.01). Results were independent of the thrombolytic agent used (alteplase or reteplase). A PA slope at 2 h higher than the average slope before thrombolysis (37.2+/-5.7) could be identified as best predictor for early (within 5-14 d, p=0.017, sensitivity 1.00, specificity 0.69) and late reocclusion (within 1 y, p=0.009, 0.88 and 0.74, respectively). CONCLUSIONS: Increased PA following coronary thrombolysis appears to be associated with early and late reocclusion. This marker could be useful in identifying patients who may benefit from more aggressive antiplatelet (such as GP IIb/IIIa receptor antagonists), interventional, or both strategies.     

'Rescue' after failed thrombolysis for acute myocardial infarction

Prompt restoration of coronary artery patency in acute myocardial infarction is associated with substantial improvements in morbidity and mortality. The pivotal role of thrombolysis and aspirin in achieving these goals is well established. However, despite the success of thrombolytic therapy in large trials, clinical assessment in individual patients often suggests that reperfusion has not occurred after initial therapy. This review considers the validity of such bedside predictions and discusses whether such patients should be managed differently.     

Incidence of hibernating myocardium after acute myocardial infarction treated with thrombolysis

OBJECTIVE: To establish the incidence of hibernating myocardium after myocardial infarction treated with thrombolysis and to observe differences in the clinical outcome between patients with and without hibernating tissue. METHODS: 41 patients underwent gated positron emission tomography with 18-fluorodeoxyglucose and 13N-ammonia at a median of eight days after first myocardial infarction. RESULTS: All 41 subjects had a matched perfusion-metabolism deficit in the region of myocardium indicated as the site of infarction by an electrocardiograph; 32 patients (78%) had scans which also showed at least one area of reduced blood flow and contraction with a concomitant increase in glucose uptake, representing hibernating myocardium. Patients were followed up at a median of six months: all 41 were alive and none had sustained a further infarct or cardiac arrhythmia; 17 subjects with hibernating tissue (53.1%) and two without (25%) reported chest pain after myocardial infarction. CONCLUSIONS: Hibernating myocardium is relatively common shortly after myocardial infarction treated with thrombolysis. It does not influence mortality or the incidence of postinfarction chest pain.     

Arrhythmias associated with acute myocardial infarction and thrombolysis

Ninety percent of patients with acute myocardial infarction have some cardiac rhythm abnormality, and approximately twenty-five percent have cardiac conduction disturbance within 24 hours following infarct onset. Almost any rhythm disturbance can be associated with acute myocardial infarction, including bradyarrhythmias, supraventricular tachyarrhythmias, ventricular arrhythmias, and atrioventricular block. With the advent of thrombolytic therapy, it was found that some rhythm disturbances in patients with acute myocardial infarction may be related to successful coronary artery reperfusion. This article addresses the role and treatment of arrhythmias and conduction disturbances that complicate the course of patients with acute infarction and thrombolysis.     

Fast track thrombolysis in acute myocardial infarction: a quality improvement project

To understand the clinical efficacy of traditional anti-rheumatic herbal medicines on acute and severe arthritis or immune diseases, four herbal formulas and one herb were tested in vitro to determine their effects on prostaglandin E2 (PGE2) and interleukin 2 (IL2). Peripheral blood mononuclear cells from healthy subjects were incubated with different concentrations of four herbal formulas including Shaur Yau Gan Tsao Tang (SYGTT), Shang Jong Shiah Tong Yong Tong Feng Wan (SJSTY), Shu Jin Lih An Saan (SJLAS), Ma Shing Yih Gan Tang (MSYGT) and one herb, Tripterygium wilfordii (T2) with and without mitogen stimulation. PGE2 and IL2 from culture supernatant were measured by enzyme immunoassay. The results showed that SYGTT, SJSTY, SJLAS at concentration of 100 microg and MSYGT at 500 microg/ml can significantly inhibit PGE2 release (P < 0.05) from mononuclear cells. However, T2 at 2 microg/ml expressed the same response. For the inhibition of IL2, the concentration of SYGTT, SJSTY and SJLAS must exceed 100 symbol microg/ml. MSYGT failed to inhibit IL2 at even concentrations of 500 microg/ml but T2 at a very low concentration (0.6 microg/ml) could strongly inhibit it. The findings suggest that the majority of traditional anti-rheumatic herbal formulas or herbs, except for T2, should not be used to treat acute and critical arthritis or immune diseases.     

Secondary prevention practices after acute myocardial infarction in a large city hospital

Increasingly, health care workers are being threatened and physically attacked by the people they are trying to help. What can physicians do to protect themselves and their coworkers?     

Withholding thrombolysis in patients with diabetes mellitus and acute myocardial infarction

The benefits of thrombolytic therapy in a patient with diabetes having a myocardial infarction are now well accepted but this treatment may be withheld inappropriately because of concerns about retinal haemorrhage. We therefore examined whether junior doctors alter their use of thrombolysis for the treatment of acute myocardial infarctions according to the type of diabetic retinopathy present. A questionnaire asking whether thrombolysis would be given to a 50-year-old male smoker with insulin-treated diabetes and an acute anterior MI was shown, with four unlabelled retinal photographs, to all doctors prescribing thrombolytic therapy in a south London teaching hospital and an affiliated district general hospital. In all, 24 medical SHOs, 16 medical registrars/specialist registrars, 3 medical senior registrars, and 23 casualty SHOs were interviewed. Of these 89% would thrombolyse such a patient with normal fundi, 55% with background diabetic retinopathy, 54 % if this also involved the macula, and 26% if they saw proliferative retinopathy. The more senior grades were more aggressive in their approach. As we believe that all patients with an acute anterior myocardial infarction and diabetes should be considered for thrombolysis irrespective of their retinal appearance these results suggest thrombolytic therapy is being withheld inappropriately.     

Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT Study

BACKGROUND: Successful coronary thrombolysis involves a risk for reocclusion that cannot be prevented by invasive strategies. Therefore, we studied the effects of three antithrombotic regimens on the angiographic and clinical courses after successful thrombolysis. METHODS AND RESULTS: Patients treated with intravenous thrombolytic therapy followed by intravenous heparin were eligible when a patent infarct-related artery was demonstrated at angiography < 48 hours. Three hundred patients were randomized to either 325 mg aspirin daily or placebo with discontinuation of heparin or to Coumadin with continuation of heparin until oral anticoagulation was established (international normalized ratio, 2.8-4.0). After 3 months, in which conservative treatment was intended, vessel patency and ventricular function were reassessed in 248 patients. Reocclusion rates were not significantly different: 25% (23 of 93) with aspirin, 30% (24 of 81) with Coumadin, and 32% (24 of 74) with placebo. Reinfarction was seen in 3% of patients on aspirin, in 8% on Coumadin, and in 11% on placebo (aspirin versus placebo, p < 0.025; other comparison, p = NS). Revascularization rate was 6% with aspirin, 13% with Coumadin, and 16% with placebo (aspirin versus placebo, p < 0.05; other comparisons, p = NS). Mortality was 2% and did not differ between groups. An event-free clinical course was seen in 93% with aspirin, in 82% with Coumadin, and in 76% with placebo (aspirin versus placebo, p < 0.001; aspirin versus Coumadin, p < 0.05). An event-free course without reocclusion was observed in 73% with aspirin, in 63% with Coumadin, and in 59% with placebo (p = NS). An increase of left ventricular ejection fraction was only found in the aspirin group (4.6%, p < 0.001). CONCLUSIONS: At 3 months after successful thrombolysis, reocclusion occurred in about 30% of patients, regardless of the use of antithrombotics. Compared with placebo, aspirin significantly reduces reinfarction rate and revascularization rate, improves event-free survival, and better preserves left ventricular function. The efficacy of Coumadin on these end points appears less than that of aspirin. The still-high reocclusion rate emphasizes the need for better antithrombotic therapy in these patients.     

Angiographic evidence of hemorrhagic myocardial infarction after intracoronary thrombolysis with streptokinase

The reperfusion of acutely ischemic myocardium by intracoronary streptokinase thrombolysis is an exciting new therapy for acute myocardial infarction (MI). It appears that successful thrombolysis and reperfusion in the first few hours after acute coronary occlusion may salvage myocardium and possibly improve prognosis. A potential adverse effect of reperfusion is the production of hemorrhage in the area of myocardial necrosis. We report on a patient with prompt, successful coronary thrombolysis by streptokinase infusion who showed angiographic evidence of a hemorrhagic MI.     

Use of composite endpoints in thrombolysis trials of acute myocardial infarction

Although preventing early mortality following acute myocardial infarction (MI) is the most important goal of thrombolytic therapy, insistence on its use as the only or principal endpoint in trials of acute MI will limit the number of new thrombolytic-antithrombotic regimens that can be tested, and thus may inhibit future progress of this important area of cardiovascular therapeutics. Trials of thrombolytic therapy over the past decade, as discussed in this article, have demonstrated that: (1) thrombolytic therapy improves both mortality and intermediate endpoints, and (2) intermediate nonfatal endpoints are strongly linked to long-term mortality. Taken together, these facts provide strong evidence that intermediate nonfatal events can be used as valid endpoints in future trials of thrombolytic therapy. The unsatisfactory outcome composite endpoint, which incorporates mortality and important intermediate endpoints, will make it possible to compare innovative new regimens in much smaller trials. Ultimately, both of these approaches (i.e., megatrials using a mortality endpoint and smaller trials utilizing a composite unsatisfactory outcome endpoint) can be used in a complementary fashion. A new regimen could first be tested using the unsatisfactory outcome endpoint; if it showed particular promise, it could then become a candidate for testing in a megatrial. Conversely, if it did not prove better than standard regimens, futile research in tens of thousands of patients might be prevented. Thus, the use of composite endpoints will expand the number of new thrombolytic-antithrombotic regimens that can be tested and, it is hoped, accelerate progress in the treatment of acute MI.     

Increased levels of erythropoietin in the initial phase of acute myocardial infarction

BACKGROUND: It's know that cardiopulmonary function affects the kidney perfusion and that erythropoietin (EPO) release depends on it. We want to determine the plasma level of EPO in the acute phase of myocardial infarction (AMI). SUBJECTS AND METHODS: A transversal trial was carried out in 37 male patients with AMI aged between 31 and 84. We studied the following variables: cardiovascular risk factors, time lapse from beginning of symptoms until hospital arrival, transcutaneous oxygen saturation (ST02) and EPO plasma levels. 16 healthy males were used as control group. RESULTS: Patients with AMI have different EPO levels than control group (25/37 vs 0/16) (18.90 +/- 8.43 mUI/ml vs 9.70 +/- 3.48 mUI/ml respectively p < 0.001). Hyperintense patients have higher EPO levels than normotense ones (18.53 +/- 8.28 mUI/ml vs 12.88 +/- 7.29 mUI/ml p < 0.05). Hypercholesterolemic patients have higher EPO level than normocholesterolemic ones (19 +/- 8.88 mUI/ml vs 12.40 +/- 6.75 mUI/ml p < 0.01). There were no difference between smokers and no smokers. We didn't find correlation between time lapse and EPO levels. CONCLUSION: The trial remarks EPO levels increase during the initial phase of AMI and it is higher in hypertensive and hypercholesterolemic patients.     

Hyperbaric oxygen and thrombolysis in myocardial infarction: the ''HOT MI'' randomized multicenter study

Reactions mediated by the brain are part of the response to intraperitoneal administration of endotoxin, a model of gram-negative bacterial infection. To test the hypothesis that a compromised blood-brain barrier (BBB) may contribute to these reactions, the integrity of the BBB was measured following lipopolysaccharide administration. Rats received intraperitoneal injections of 50 microg/kg or 2 mg/kg of endotoxin. Brain uptake of a macromolecular vascular marker, 3H-labelled rat serum albumin, and of a poorly permeable low molecular weight substance, [14C]sucrose, was then measured with the intravenous bolus injection method. Compared to controls, neither dose of endotoxin affected the BBB permeability for these tracers. This was true when brain uptake was measured 5 min or 2 h after lipopolysaccharide injection. It is concluded that intraperitoneal endotoxin even at a high dose does not acutely disrupt the BBB.     

Complex stenosis morphology predicts late reocclusion during follow-up after myocardial infarction in patients with patent infarct-related coronary arteries

BACKGROUND: Whether angiographic morphology of infarct-related residual stenoses continues to affect prognosis after discharge is not known. METHODS: We studied 175 patients after their myocardial infarction who required nonurgent coronary angioplasty for residual myocardial ischemia. The findings at diagnostic coronary angiography were compared with those before angioplasty (mean of 7 months later). Infarct-related stenoses were classified as complex or smooth. Stenosis progression was defined as >0.5 mm diameter reduction. RESULTS: One hundred twenty-one (69%) infarct-related stenoses were complex. At restudy, total occlusion was found in 41 (35%) of the infarct-related complex stenoses compared with 7 (13%) smooth stenoses (P = .001). Reocclusion occurred in 16 (55%) of 29 complex infarct-related stenoses with thrombus, compared with 25 (28%) of 88 without thrombus (P = .01). During follow-up, 46 patients (26%) had cardiac events. Of these, 70% had complex lesions at study entry compared with 30% smooth (P < .05). CONCLUSIONS: Residual angiographically complex stenoses after an uncomplicated myocardial infarction are associated with a greater risk of reocclusion and may predispose to coronary events at follow-up.     

Analysis of reperfusion by thrombolysis of the artery responsible for acute myocardial infarction

OBJECTIVE: To analyze the role of the culprit coronary artery in myocardial infarction, its evolution and mortality. And to correlate with clinical criteria of reperfussion. MATERIALS AND METHODS: We included patients with clinical diagnosis of acute myocardial infarction (MI) treated with thrombolytic therapy, and coronariography. We used the TIMI study angiographic scale to evaluate the level of permeability of the culprit artery. RESULTS: Of 473 patients with of acute MI; coronariography was made in 377. The most frequent culprit vessel was anterior descending artery in 168 patients (45%) and right coronary artery in 139 patients (36%). In 276 patients the culprit vessel was permeable (73%). Of them in 30 patients, had TIMI 1 alterations, TIMI 2 in 97 patients, had TIMI 3 in 148 patients, only 102 patients had TIMI 0. In anterior MI the most frequent reperfussion arrhythmia was ventricular ectopic beats followed by slow ventricular tachycardia and ventricular tachycardia in 54%, ventricular fibrillation was observed only in six patients, of whom TIMI scale was 2 and 3 in five patients. In inferior MI, ventricular ectopic beats and slow ventricular tachycardia was seen in 25% of patients. In patients with permeable culprit artery we observed significant depression of ST segment, (159 patients, 42%), and significant increase in CK-MB levels, seen in 191 patients (51%). In the group of patients with total occlusion of the culprit artery, twenty-one (30%) had left ventricular disfuntion, and only six of them were in cardiogenic shock. In the group of patients with permeable culprit artery only two percent had cardiogenic shock. Therefore the analysis of the clinical evolution is the maia marker to take into consideration to send patients to early coronary arteriography with the objective to look for other therapeutic alternatives.