Acute myocardial infarction: failed thrombolysis revisited

The prognosis following acute myocardial infarction is dependent upon the presence of adequate blood flow in the infarct-related vessel. All too often, this is not achieved by thrombolytic therapy ('failed thrombolysis'). Diagnosis of failed thrombolysis is difficult and the optimum management is currently unclear.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Diffuse pulmonary hemorrhage after fibrinolytic therapy for acute myocardial infarction

Occurrence of Non Hodgkin's lymphoma (NHL) in pregnancy is very rare. A 24-year-old woman with NHL stage IVB complicating pregnancy is presented. The diagnosis was made by biopsy at 27 weeks. The patient received combination chemotherapy which led to remission of the disease. The baby was delivered by an emergency caesarean section, due to fetal distress at 31 weeks. Unfortunately after a short period of remission a relapse occurred and magnetic resonance imaging (MRI) showed cerebral involvement, indicating a poor prognosis. She died seven months later from disseminated disease.     

Thrombolysis for acute myocardial infarction

Thrombolytic therapy has been a major advance in the management of acute myocardial infarction. Unfortunately, it continues to be underused or is administered later than is optimal. Thrombolytic therapy works by lysing infarct artery thrombi and achieving reperfusion, thereby reducing infarct size, preserving left ventricular function, and improving survival. The most effective thrombolytic regimens achieve angiographic epicardial infarct-artery patency in only approximately 50% of patients within 90 minutes. Bleeding requiring transfusion occurs in approximately 5% of patients and stroke in approximately 1.8% with these regimens, which include adjunctive aspirin and intravenous heparin. There are several ways in which reperfusion rates and thus patient outcomes might be improved, such as different dosing regimens of established agents; combinations of different agents; improved adjunctive therapy such as direct antithrombin agents, low-molecular-weight heparin, or glycoprotein IIb/IIIa receptor antagonists; or the development of novel thrombolytic agents with enhanced fibrin specificity, resistance to native inhibitors, or prolonged half-lives allowing bolus administration. All of these strategies are being tested in clinical trials. The best approach currently is to administer thrombolytic therapy as soon as possible to all patients without contraindications who present within 12 hours of symptom onset and have ST-segment elevation on the ECG or new-onset left bundle-branch block, unless an alternative reperfusion strategy is planned.     

Fatal spontaneous spinal epidural hematoma following thrombolysis for myocardial infarction

BACKGROUND: This is the first communication of a fatal spontaneous spinal epidural hematoma following thrombolysis. CLINICAL PRESENTATION: Spine pain may precede neurologic deterioration by many hours. The diagnosis can be accurately made with axial computed tomography (CT) of the involved spinal segment. TREATMENT: Emergency surgery is the treatment for this condition, but conditions such as the acute stage of a myocardial infarction or intraoperative bleeding difficulties due to iatrogenic coagulopathy, the degree of preoperative neurologic deficit, and the timing of surgery must be cautiously considered. CONCLUSIONS: Neurosurgeons will be faced with another devastating complication of thrombolytic therapy, as long as the available drugs are being used. Early clinical suspicion and availability of CT or magnetic resonance imaging for prompt diagnosis are essential to initiate appropriate medical therapy and timely surgery. New strategies must include the development of completely fibrin-specific thrombolytics and drugs that may rapidly reverse the systemic and local clotting disorder.     

ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction

BACKGROUND: The goal of thrombolytic treatment in acute myocardial infarction is reperfusion of the infarct-related coronary artery. Duteplase is a double-chain recombinant tissue-type plasminogen activator. Its efficacy and safety were evaluated in patients with acute myocardial infarction treated within 4 h of onset of chest pain in this multicentre, open, non-controlled trial. METHODS AND RESULTS: A total of 273 patients were enrolled and treated with duteplase 0.6 MU.kg-1 over 4 h, with concomitant oral aspirin and intravenous heparin. Coronary arteriography was performed at 60 min, 90 min and approximately 24 h after the start of duteplase infusion to assess the perfusion grade (TIMI scoring) of the infarct-related coronary artery. Safety was assessed by monitoring patients closely for bleeding and for all other adverse experiences during the 72-h study period. Reinfarction during the study period was also recorded, and deaths at any time during the period in hospital were documented. TIMI grade 2 or 3 patency of the infarct-related coronary artery at 90 min was achieved in 70% of the patients and 7% of these "patent' infarct-related coronary arteries had reoccluded by 20 to 36 h. Clinical reinfarction during the 72-h study period was observed in 7%. Total in-hospital mortality was 8%. Serious or life-threatening bleeding occurred in 4% of the patients. There was one haemorrhagic stroke, and this was fatal. CONCLUSIONS: Weight-adjusted duteplase infusion, together with oral aspirin and intravenous heparin, in acute myocardial infarction resulted in patency of the infarct-related coronary artery and a safety profile comparable to those reported for the other form of tissue-type plasminogen activator, alteplase. However, there remains a problem with reocclusion and reinfarction after initially successful thrombolysis.     

Thrombolytic therapy for acute myocardial infarction

Numerous factors must be considered when determining the formulary status of thrombolytic agents for the treatment of acute myocardial infarction. Defined treatment options, predicted outcomes, and the economic consequences of this disorder continue to evolve from clinical trials. Pharmacists have a major role in delivering patient care, with responsibility for evaluating, procuring, and monitoring thrombolytic agents and drug therapy in general. By participating in the development and implementation of treatment guidelines, evaluating economic and therapeutic outcomes, providing timely optimal drug therapy, and educating health care providers and the public, they contribute significantly to the health care team.