Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with acute myocardial infarction treated with alteplase and streptokinase

Peak serum C-reactive protein concentrations were measured in 146 patients randomized to receive streptokinase, alteplase, or a combination of streptokinase and alteplase in the GUSTO-I trial. Those receiving alteplase treatment had lower values than those receiving streptokinase or the combination treatment. Irrespective of treatment, complete reperfusion of the infarct-related artery (TIMI grade 3 flow) was associated with low peak serum C-reactive protein values

Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascular development of Lrp2 KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. The Lrp2 KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in the Lrp2 KO. T hi s explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans with LRP2 mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis

Ineligibility for predischarge exercise testing after myocardial infarction in the elderly

This study describes the clinical profile and prognosis of elderly patients not eligible for predischarge exercise testing. The database consisted of 133 patients 55-64 years of age, and 111 patients older than 64 years of age who survived an acute myocardial infarction. Follow-up was one year. In the younger age group, 24 (18%) patients were unable to perform the test, in contrast to 63 (57%) of the elderly subjects. In these two groups, one-year mortality rates were 13% and 37%, compared with 6% and 4% for the respective patients eligible for stress testing. Clinical profile and radionuclide ejection fraction between ineligible patients in both age groups were similar. Ejection fraction measurement was the best predictor of late mortality in those patients who did not have an exercise test. It is concluded that ineligibility for predischarge exercise test identifies a high-risk group, especially in patients older than 64 years of age

Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency

BACKGROUND: The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. METHODS: A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment. RESULTS: Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator). CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial

Value of predischarge data for the prediction of exercise capacity after cardiac rehabilitation in patients with recent myocardial infarction

The aim of this study was to assess whether data related to predischarge clinical examinations, resting radionuclide ventriculography and symptom-limited bicycle ergometry can predict the achievement of a normal exercise capacity after a rehabilitation program in patients with a recent myocardial infarction. The study population consists of 141 consecutive patients who completed a 3-month training program. Patients with heart failure and/or severe angina were excluded. The rehabilitation program included two training sessions weekly during the 3 months. W

Relative value of clinical variables, bicycle ergometry, rest radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring at discharge to predict 1 year survival after myocardial infarction

The relative value of predischarge clinical variables, bicycle ergometry, radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring for predicting survival during the first year in 351 hospital survivors of acute myocardial infarction was assessed. Discriminant function analysis showed that in patients eligible for stress testing the extent of blood pressure increase during exercise slightly improved the predictive accuracy beyond that of simple clinical variables (history of previous myocardial infarction, persistent heart failure after the acute phase of infarction and use of digitalis at discharge), whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring did not. The predictive value for mortality was 12% with clinical variables alone and 15% with the stress test added. Radionuclide ventriculography and 24 hour electrocardiographic monitoring were slightly additive to clinical information in the whole group of patients independent of the eligibility for stress testing (predictive value for mortality 24% with clinical variables alone and 26% with radionuclide ejection fraction and 24 hour electrocardiographic monitoring added). It is concluded that the appropriate use of simple clinical variables and stress testing is sufficient for risk stratification in postinfarction patients, whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring should be limited to patients not eligible for stress testing

Safety and preliminary efficacy of one month glycoprotein IIb/IIIa inhibition with lefradafiban in patients with acute coronary syndromes without ST-elevation; a phase II study.

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 toward