Increased serum levels of fibrinogen degradation products due to treatment with recombinant tissue-type plasminogen activator for acute myocardial infarction are related to bleeding complications, but not to coronary patency. European Co-operative Study Groups for rt-PA.

The association of increasing serum levels of fibrinogen degradation products after recombinant tissue-type plasminogen activator (rt-PA) therapy with bleeding and early coronary patency was assessed in 242 patients with acute myocardial infarction. After administration of 5,000 IU heparin, a median of 40 mg (range 35 to 60) of double chain rt-PA was given intravenously in 90 min. Bleeding occurred in 62 patients; in 73% of patients it was observed within the 1st 24 h and 84% of events consisted of hematoma or prolonged bleeding, or both, at puncture sites. Bleeding events occurred 2.12 times as often in patients with serum levels of fibrinogen degradation products greater than 85 mg/liter as in patients with serum levels less than 22 mg/liter (95% confidence interval 1.01 to 4.43). The infarct-related coronary vessel was patent in 65% of patients at 90 min after the start of rt-PA infusion. In patients with high serum levels of fibrin(ogen) degradation products, coronary patency at 90 min after the start of rt-PA infusion was not better (13% less, 95% confidence interval - 33%, 13%) than in patients with low serum levels. This uncoupling of thrombolytic effect in terms of coronary patency and systemic fibrinogenolysis confirms the experimentally demonstrated fibrin specificity of double chain rt-PA in human subjects. Because fibrin specificity of single chain rt-PA is at least similar to that of double chain rt-PA, the observations in this analysis most likely hold also for single chain rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary patency after intravenous infusion of recombinant tissue-type plasminogen activator in acute myocardial infarction.

The relation between coronary patency after infusion of recombinant tissue-type plasminogen activator (rt-PA) and clinical and laboratory findings was assessed in patients with acute myocardial infarction. This study focused primarily on information available early in the hospitalization phase. Data were available for 243 patients who received the full dose of rt-PA and who had assessable coronary angiograms 90 min after the start of the intravenous infusion. The infarct-related vessel was scored by an independent assessment committee as being patent in 65% of patients. The left anterior descending coronary artery was involved in 53% of patients, and proximal localization of the infarct-related vessel occurred in 65%. In the majority of patients (85%), the infusion was started within 4 h of the acute event. Neither the angiographic location of the infarct-related vessel nor electrocardiographic evidence of infarct severity or location appeared to have a bearing on thrombolysis with rt-PA. Multivariate logistic regression analysis identified three independent predictors of coronary patency: hematocrit 43 to 47%, blood plasminogen level greater than or equal to 90% of normal and serum alkaline phosphatase greater than or equal to 82% of the local upper normal limit. In addition, the use of intravenous nitrates suggests a positive association with patency.

[Randomized double-blind study comparing tissue-type plasminogen activator with placebo in acute myocardial infarct]. / Randomisierte Doppelblindstudie zum Vergleich von Gewebe-Plasminogen-Aktivator mit Plazebo beim akuten Herzinfarkt.

In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.

Effect of continued rt-PA administration on the residual stenosis after initially successful recanalization in acute myocardial infarction--a quantitative coronary angiography study of a randomized trial.

Quantitative angiography was performed in 68 out of 123 patients treated with intravenous rt-PA for acute myocardial infarction. At 90 min angiography, the median minimal cross-sectional area was 1.11 mm2 and the median percentage area stenosis was 80%. A percentage area stenosis greater than 70% was seen in 78% of the patients. Patients with a patient infarct related artery at the first angiogram were randomized to receive subsequent infusions either of rt-PA + heparin or placebo + heparin. There was a persistent trend of improvement in minimal lumen diameter and percentage diameter stenosis of the residual stenosis in the infarct related artery in both treatment groups when re-examined 6-24 hours later and at the time of hospital discharge. A reduction in 'plaque area', the area between the detected and the reference contours of the infarct related segment, was more frequently seen in patients receiving a second infusion of rt-PA than in patients with no prolonged thrombolytic therapy (83% versus 57%, P less than 0.025, chi square).

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. Working capacity (WC) increased from 79 +/- 17% at hospital discharge to 105 +/- 21% of normal values after rehabilitation (P less than 0.001), by 33% on average. Ninety-five patients achieved a normal WC. Conventional predischarge clinical evaluation, resting left ventricular ejection fraction, exercise induced angina, or ST segment depression were not predictive of normal WC after rehabilitation. Predischarge WC was the single best predictor of a normal WC after rehabilitation compared to those with a persistently low WC (84 +/- 15% in patients with normal WC vs 69 +/- 14% in those with persistently low WC, P less than 0.001). Nevertheless, 49% of patients with a baseline WC of less than 80% achieved a normal WC after rehabilitation. No correlation was found between the change of WC after rehabilitation and predischarge WC or ejection fraction. Therefore, the selection of patients for cardiac rehabilitation after a myocardial infarction should be based primarily on clinical grounds. Exclusion based on exercise induced angina, ST segment depression or low resting ejection fraction at hospital discharge or at entry in the rehabilitation program is not justified.

Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate.

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed.

Incidence and prognostic implications of repetitive ventricular complexes during pre-discharge bicycle ergometry after myocardial infarction.

The clinical significance of repetitive ventricular complexes (RVCs) during pre-discharge bicycle ergometry after acute myocardial infarction has been assessed in 408 consecutive patients. RVCs occurred in 32 patients (8%). When compared to patients without RVCs, those with RVCs had a larger infarction, a higher prevalence of heart failure and late sustained ventricular tachycardia or fibrillation, a lower radionuclide ejection fraction and more frequent RVCs during pre-discharge 24-hour electrocardiographic monitoring. During a follow-up 30 patients died, 17 suddenly. Mortality was 15% (N = 5) in patients with RVCs during exercise test and 7% (N = 25) in those without RVCs. Sudden death occurred in only one patient with RVCs. When multivariate analysis was applied to clinical and exercise test data, RVCs during exercise did not predict cardiac mortality independent of variables related to left ventricular function, such as a history of previous myocardial infarction, persistence of heart failure in the late hospital phase and the extent of blood pressure rise during exercise test.

The role of the personal computer in the cardiac catheterization laboratory: an integrated approach to information management.

A personal computer-based data management system for the cardiac catheterization laboratory is described. This is a cooperative effort on the part of the Dutch academic hospitals, through the Interuniversity Cardiology Institute, to put in place a more uniform structure for data collection and reporting in the context of cooperative studies. The major design criteria included the necessity that the system provide a clear and present benefit to the users in terms of their day-to-day work. This requires a practical data entry package together with a full reporting capability, including management tools for supervision of the catheterization laboratory in general. Ancillary activities include quantitative analysis of ventriculograms and an elementary statistics package with graphics. To facilitate supportability of the system, commercially available packages for data base management, text processing, and communications have been used to advantage. After a prototype test phase involving two centers, five other centers have been equipped with similar systems and used successfully in the majority.

Prognostic value of predischarge 12 lead electrocardiogram after myocardial infarction compared with other routine clinical variables.

The prognostic value of QRS score (Selvester), ST depression, ST elevation, extrasystoles, P terminal force in V1, and QTc derived from the predischarge 12 lead electrocardiogram was assessed after myocardial infarction in 474 patients without intraventricular conduction defects, ventricular hypertrophy, or atrial fibrillation. The usefulness of these results in risk assessment was compared with that of other clinical data. During follow up 45 patients died. Logistic regression analysis showed that QRS score, ST depression, and QTc were independently predictive of cardiac mortality. When multivariate analysis was applied to clinical and electrocardiographic data together, however, the 12 lead electrocardiogram did not provide independent information additional to that provided by other routine clinical findings and laboratory tests such as a history of previous myocardial infarction, clinical signs of persistent heart failure, indication for digitalis or antiarrhythmic drugs at discharge, and enlarged heart on chest x ray. In conclusion, the electrocardiogram has important prognostic value; however, it is not powerful enough to further improve the risk assessment of post-infarction patients.

Prediction of 1-year outcome after complicated and uncomplicated myocardial infarction: Bayesian analysis of predischarge exercise test results in 300 patients.

After myocardial infarction (MI), the additive prognostic value of exercise variables to clinical variables has been questioned. The merits of a symptom-limited predischarge exercise test were therefore evaluated in clinically defined subgroups of patients. Exercise tests were consecutively performed by 208 survivors of uncomplicated MI (no heart failure, postinfarction angina, recurrent infarction, or late arrhythmias) and by 92 survivors of complicated MI. After uncomplicated MI (1-year mortality rate 4%), an achieved workload greater than 70% of age-predicted maximum identified 145 patients at very low risk (predictive value for survival 98%). After complicated MI (1-year mortality rate 13%), an exaggerated heart rate response was the best predictor of outcome, but had low (92%) predictive value of survival at 155 bpm. It is concluded that stress testing has only limited value after complicated MI. After uncomplicated MI, exercise variables are extremely helpful in identifying patients at very low risk in whom further investigations are not warranted.

Early post-infarction angina. Incidence and prognostic relevance.

Early post-infarction angina (2-15 days after infarction) occurred in 132 out of 616 consecutive coronary care unit admissions for acute myocardial infarction within 24 h from onset of symptoms. Patients with early post-infarction angina more often had a history of stable pre-infarction angina as well as late post-infarction angina. Coronary artery disease was more extensive in patients with early post-infarction angina compared with those without angina. Forty-five patients with angina were treated before hospital discharge with coronary artery bypass (CABG) (N = 35) or percutaneous transluminal coronary angioplasty (PTCA) (N = 10). Survival and incidence of non-fatal reinfarctions during 1-year follow-up was similar in patients with and without early post-infarction angina (respectively 83% versus 82% and 13% versus 11%). The incidence of angina in the follow-up was higher in the whole group of patients with early post-infarction angina then in patients without angina (53% versus 32%, P less than 0.001), but was lowest (22%) in the subset who underwent CABG or PTCA before discharge. In patients with early post-infarction angina, age, left ventricular dysfunction, extensive coronary artery disease, stable pre-infarction angina and electrocardiographic ischaemic changes distant from the infarct zone during angina were significantly associated with a poor survival.

Effect of flecainide on regional left ventricular wall motion after acute intravenous, acute oral and chronic oral administration late after coronary artery bypass grafting.

Epicardial marker motion was measured in 14 patients before flecainide administration, immediately after an intravenous dose of 2 mg/kg over 15 minutes (maximum 150 mg) and 15 minutes thereafter. Platinum epicardial markers had been implanted more than 4 years earlier at the time of coronary artery bypass grafting. Maximal and minimal marker separation (Lmax and Lmin) during the cardiac cycle were measured and regional shortening fraction (Lmax - Lmin)/Lmax) was determined as a percentage. After intravenous flecainide, a significant increase in end-diastolic (immediately after 2.8%; after 15 minutes 2.1%) and end-systolic (3.6% and 3.2%) regional dimensions was observed, together with a decrease in regional myocardial shortening (9.3% and 9.0%). One week later, after a single oral dose of 200 mg of flecainide, Lmax and Lmin had increased 2.4% and 2.7%, while regional myocardial shortening did not differ significantly from baseline values. In 10 patients measurements were repeated after 6 weeks of chronic oral treatment with 300 mg/day. Despite plasma flecainide levels similar to those after intravenous administration, no significant changes in end-diastolic and end-systolic dimensions or regional shortening fraction were observed. Thus, acute intravenous or oral flecainide administration increases regional end-diastolic and end-systolic dimensions, but only intravenous administration decreases regional shortening fraction. Values during chronic administration indicate that regional myocardial function is more affected at the time of rising or acutely changing flecainide plasma levels than when stable plasma levels are achieved.

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.

Double-blind randomised trial of intravenous tissue-type plasminogen activator versus placebo in acute myocardial infarction.

In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.

Surgical versus non-surgical management of patients soon after acute myocardial infarction.

Of 510 patients admitted to hospital with acute myocardial infarction, 34 had coronary artery bypass grafting before discharge (6-43 days (median 20) after infarction). The patients who were given grafts generally had a smaller infarction with less functional impairment than the 476 patients who were not. The outcome of coronary artery bypass grafting was investigated in a retrospective matched pair study. Patients were matched on the basis of the presence of postinfarction angina, left ventricular ejection fraction, location of the infarction, peak creatine kinase activity, Killip clinical class, and severity of coronary disease with 34 patients who were given medical treatment only. At one year follow up fewer of the operated patients had symptoms than did the matched non-operated patients. Survival at one year in the operated and non-operated groups respectively was 94% vs 91%; angina within one year occurred in 3% vs 68%; congestive heart failure in 3% vs 6%; and 0% vs 32% were referred for later bypass grafting or coronary angioplasty. It is concluded that coronary artery bypass grafting can be performed safely soon after myocardial infarction provided that left ventricular function is not seriously compromised. Such treatment is more effective than medical treatment for relief of angina during the first year after infarction.

Prognosis of patients with different peak serum creatine kinase levels after first myocardial infarction.

The extent to which patients with low peak serum creatine kinase (CK) at their first myocardial infarction differ from patients with high CK levels in terms of risk for subsequent ischaemic events was investigated in 266 patients who survived the first 48 h from the onset of infarction. All patients were followed up for one year. Four groups were formed based on peak CK less than or equal to 200, 201-400, 401-800 and greater than 800 IU l-1. During follow-up the incidence of mortality was 15% (N = 39), non-fatal re-infarction 9% (N = 23), and angina 53% (N = 140). Hospital mortality was significantly higher (P less than 0.02) in the highest CK-group (16%), but the incidence of non-fatal re-infarction, angina pectoris and late mortality was similar in the four groups. In hospital survivors, ischaemic ST-changes during pre-discharge symptom limited bicycle stress test and multiple vessel disease were equally distributed in all four groups. We conclude that while hospital mortality is directly related to peak CK, there is no relationship between peak CK and late mortality, non-fatal re-infarctions, or recurrent angina. Accordingly, diagnostic and therapeutic procedures in the individual patients are not influenced by the amount of serum CK released during acute infarction.

Prediction of mortality during the first year after acute myocardial infarction from clinical variables and stress test at hospital discharge.

The predictive value of a predischarge symptom-limited stress test was studied in 405 consecutive survivors of acute myocardial infarction (AMI). Three hundred patients performed bicycle ergometry; 105 could not perform it. Among these latter 105 patients, the stress test was contraindicated in 43 because of angina or heart failure and in 62 because of noncardiac limitations. One-year survival was 44% in the "cardiac-limited" group (19 of 43) and 92% in the "non-cardiac-limited" group (57 of 62). One-year survival among the patients who performed an exercise test at discharge was 93% (280 out of 300). The best stress test predictor of mortality by univariate analysis was the extent of blood pressure (BP) increase: 42 +/- 24 mm Hg in 280 survivors vs 21 +/- 14 mm Hg in 20 nonsurvivors (p less than 0.001). Among the 212 patients in whom BP increased 30 mm Hg or more, mortality was 3% (n = 6), while it was 16% (n = 14) among the 88 patients in whom BP increased less than 30 mm Hg. Angina, ST changes and arrhythmias were not as predictive. Stepwise discriminant function analysis showed inadequate BP increase to be an independent predictor of mortality. A high-risk group can be identified at discharge on clinical grounds in patients unable to perform a stress test, whereas intermediate- and low-risk groups can be identified by the extent of BP increase during exercise.

Randomised trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Report from the European Cooperative Study Group for Recombinant Tissue-type Plasminogen Activator.

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1 500 000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the differences ranges from +/- 30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.