Improvement in long-term prognosis of elderly patients with acute myocardial infarction after the introduction of intravenous thrombolytic therapy

Survival rate from a "thrombolytic" period of 351 patients above 66 years of age with acute myocardial infarction (AMI) was compared with that of 289 patients from a "prethrombolytic" period. The two groups were comparable regarding sex, age, previous AMI, cerebrovascular events, morbidity and mortality during admission. Survival rates after four years were 45.0% in the "thrombolytic" group and 38.4% in the "prethrombolytic" group (p = 0.047, log rank test). Using the Cox proportional hazard analysis, thrombolytic therapy was shown to be an independent prognostic predictor in "the thrombolytic population" with a relative risk of death from day 30 to end of follow-up of 0.4 (95% confidence interval 0.2-0.8). No interaction was found between age and thrombolysis. Although only one-fifth of the patients with AMI were eligible for thrombolysis, this treatment may have contributed to the improved long-term survival.     

Percutaneous transluminal coronary angioplasty in acute myocardial infarction. A prospective controlled study

In the present study we compared the outcome of primary percutaneous coronary angioplasty (PTCA) (PTCA without prior or concomitant administration of thrombolytic drugs) in 82 consecutive patients with acute myocardial infarction (AMI) with the outcome of 82 AMI patients, who were treated with intravenous thrombolysis. The thrombolysis patients were prospectively matched to the angioplasty patients regarding age, sex, duration of symptoms and infarct localisation. The in-hospital mortality was 3.7% in the PTCA group versus 4.9% in the thrombolysis group. Thrombolysis-treated patients had increased use of diuretics and ACE-inhibitors as compared to PTCA-treated patients. The mean ejection fraction was 52 +/- 11% in the PTCA group versus 47 +/- 10% (p = 0.01) in the thrombolysis group. We conclude that initial Danish experience with primary PTCA is promising, and that this treatment may favourably affect the outcome of acute myocardial infarction.     

Usefulness of ST-segment depression in non-infarct-related electrocardiographic leads in predicting prognosis after thrombolytic therapy for acute myocardial infarction

This study investigated both the in-hospital and long-term prognostic significance of ST-segment depression in non-infarct-related leads in patients who received thrombolytic therapy after acute myocardial infarction (AMI). We evaluated 221 consecutive patients who were admitted with their first AMI and underwent thrombolysis. Patients were followed for an average of 31 months and were classified into 3 groups: group 1 included 51 patients with persistent ST-segment depression, group 2 had 97 patients with transient ST-segment depression, and group 3 consisted of 73 patients without ST-segment depression (absent). Group 1 had significantly worse long-term survival during follow up by Kaplan-Meier analysis (55%) versus group 2 (81%) and group 3 (94%) (p = 0.0004) and higher event rates. This prognostic significance seemed to be maintained in both the anterior and inferior wall AMI groups. Multivariate analysis, using the Cox model, showed that Killip class, in-hospital left ventricular ejection fraction, and the persistence of ST-segment depression on the predischarge electrocardiogram (group 1) were independent predictors of survival. ST-segment depression in non-infarct-related leads on the predischarge electrocardiogram is an independent risk factor for worse long-term survival after anterior as well as inferior AMI treated with thrombolytic therapy.     

Three cases of tuberculosis after heart transplantation in Spain

The fibrinolytic capacity of patients with acute myocardial infarction (AMI) is known to be impaired. The primary regulatory element of the fibrinolytic system is plasminogen activator inhibitor (PAI). It has been previously observed that there are 2 peaks in the plasma PAI level of AMI patients at 4h and 16h after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Lanoteplase/SUN9216 is a mutant tPA with a biological half-life longer than that of rtPA. Thrombolytic therapy with mutant tPA or rtPA was carried out consecutively in 21 patients with AMI (8 patients as the mutant tPA group, and 13 patients as the rtPA group). The recanalization time of the mutant tPA group was significantly faster than that of the rtPA group (16.1 +/- 3.9 min vs 39.6 +/- 4.8 min, p<0.01). The PAI activity at 4h after the initiation of thrombolysis was significantly lower in the mutant tPA group than in the rtPA group (8.74 +/- 5.46IU/L vs 26.74 +/- 3.35 IU/L, p<0.01). There was a one mild peak in serial plasma PAI activity levels 24h after the initiation of thrombolysis. The results suggest that thrombolytic therapy with mutant tPA reduced the impairment of fibrinolytic capacity. The mutant tPA gives faster recanalization and lower PAI activity after successful thrombolysis, compared with rtPA.     

Prognostic significance of ST segment shift early after resolution of ST elevation in patients with myocardial infarction treated with thrombolytic therapy: the GUSTO-I ST Segment Monitoring Substudy

OBJECTIVES: We sought to study the relation between recurrent ST segment shift within 6 to 24 h of initial resolution of ST elevation after thrombolytic therapy and 30-day and 1-year mortality. BACKGROUND: Rapid and stable resolution of ST segment elevation in relation to thrombolytic therapy in patients with an acute myocardial infarction is an indicator of culprit artery patency. Whether recurrence of ST segment shift during continuous ST monitoring after initial resolution is related to poor prognosis has not been studied. METHODS: ST segment monitoring was performed within 30 min after thrombolytic therapy for acute myocardial infarction. The predictive value of a new ST segment shift (assessed as > or = 0.1-mV deviation from the baseline) 6 to 24 h after thrombolytic therapy was studied with respect to 30-day and 1-year mortality. RESULTS: Of 734 patients, 243 had a new ST segment shift (33%). The 30-day mortality rate in patients with an ST shift (7.8%) was significantly higher than that in patients without an ST shift (2.25%, p = 0.001), as was the 1-year mortality rate (10.3% vs. 5.7%, respectively, p = 0.025). Multivariable analysis revealed an independent predictive value of ST shift with respect to 30-day mortality (p = 0.008), even after consideration of multiple clinical risk factors in the overall Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO)-I mortality model (p = 0.0001). Moreover, the duration of the ST shift bore a direct relation with 1-year mortality (p = 0.008). CONCLUSIONS: Detection of ST segment shift early after thrombolytic therapy for acute myocardial infarction is a simple, noninvasive means of identifying patients at high risk and is superior to other commonly assessed clinical risk factors. Thus, patients with a new ST shift after the first 6 h, but within 24 h, represent a high risk group that may benefit from more aggressive intervention, whereas patients without evidence of an ST shift represent a low risk subgroup.     

Reocclusion: the flip side of coronary thrombolysis

Since the introduction of thrombolytic therapy for acute myocardial infarction, the incidence of coronary artery reocclusion has been intensively studied. Also, the prediction and diagnosis of reocclusion by angiographic and clinical variables, as well its invasive and pharmacologic prevention, have gained much attention. By angiographic definition, reocclusion requires three angiographic observations: one with an occluded artery, one with a reperfused artery and a third for the assessment of subsequent occlusion (true reocclusion). Since the introduction of early intravenous reperfusion therapy, most studies use only two angiograms: one with a patent and one with a nonpatent infarct-related artery. A search for all published reocclusion studies revealed 61 studies (6,061 patients) with at least two angiograms. The median time interval between the first angiogram after thrombolysis and the second was 16 days (range 0.1 to 365). Reocclusion was observed in 666 (11%) of 6,061 cases. Interestingly, the 28 true reocclusion studies showed an incidence of reocclusion of 16 +/- 10% (mean +/- SD), and the 33 studies with only two angiograms 10 +/- 8% (p=0.04), suggesting that proven initial occlusion of the infarct-related artery is a risk factor for reocclusion after successful thrombolysis. The other predictors for reocclusion are probably severity of residual stenosis of the infarct-related artery after thrombolysis and perhaps the flow state after lysis. Reocclusion is most frequently seen in the early weeks after thrombolysis. The clinical course in patients with reocclusion is more complicated than in those without this complication. Left ventricular contractile recovery after thrombolysis is hampered by reocclusion. Routine invasive strategies have not been proven effective against reocclusion. In the prevention of reocclusion, both antiplatelet and antithrombin strategies have been tested, including hirudin and hirulog, but the safety of these agents in thrombolysis is still questionable. Thus, reocclusion after thrombolysis is an early phenomenon and is more frequent after proven initial occlusion of the infarct-related artery. Reocclusion can be predicted by angiography after thrombolysis. Because reocclusion is detrimental, strategies to prevent it should be developed and carried out after thrombolytic therapy for acute myocardial infarction as soon as they are deemed safe.     

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase

BACKGROUND: It has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI). METHODS AND RESULTS: Consecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA. CONCLUSIONS: These results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.     

Thrombolysis following myocardial infarct. European Secondary Prevention Study

For evaluation of the management of patients with acute myocardial infarction, all cases of ten Zurich hospitals (278, 184 men and 94 women) in the period from 1 January to 31 March 1993 were analyzed retrospectively. 223 patients were released from hospital, 55 died. A follow-up was done 6 months after the patient's discharge by means of a questionnaires to the family doctor (return rate: 65.9%). 48.5% of patients were referred to hospital within the first 6 h. after onset of symptoms, 64% within the first 12 h. 28% (n = 76) of the patients received a thrombolytic therapy, of which 91% (n = 69) got streptokinase and 9% (n = 7) got tissue plasminogen activator. In 81% of the cases the thrombolytic therapy was done within the first hour in hospital, in accumulated 97% of the cases within two hours. In the age group under 65 years (39% of the patients, n = 109), 48 patients received thrombolysis (odds ratio [OR] = 1.0). In the age group between 65 and 74 years (24.5 % of the patients, n = 68), 19 patients received thrombolysis (OR: 0.49; 95% CI: 0.42-0.99; p < 0.05), and in the age group over 74 years (36.5% of the patients, n = 101), 9 patients were received thrombolysis (OR: 0.12; 95% CI: 0.05-0.28; p < 0.0001). 31% of the patients (n = 46) received a coronary angiography, 15% (n = 22) had coronary angioplasty, and 11% (n = 1) received coronary bypass surgery. There is evidence that there should be more importance attached to early hospitalization, if acute myocardial infarction is suspected. Thereby age alone should be considered as a contraindication for thrombolytic therapy. The issue of assumed underuse of thrombolytic therapy should be investigated all over Switzerland.     

Does PTCA in acute myocardial infarction affect mortality and reinfarction rates? A quantitative overview (meta-analysis) of the randomized clinical trials

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is often performed after acute myocardial infarction (AMI) either as an adjuvant to thrombolytic therapy or instead of thrombolysis. The effect of PTCA in AMI on mortality and reinfarction has remained unclear, with the available randomized trials indicating inconsistent results. METHODS AND RESULTS: A systematic overview (meta-analysis) of the randomized trials was conducted to assess the effect of PTCA in AMI on mortality and reinfarction rates. Data from 7 trials in which primary PTCA was evaluated and 16 trials in which PTCA after thrombolysis was studied were included in this overview, comprising a total of 8496 patient. The trials represented different approaches to the timing of PTCA after AMI. The trials of PTCA after thrombolytic therapy were also categorized according to the different protocols with respect to the routine or elective character of PTCA in the invasive group. A reduction in short-term (6 week) mortality (odds ratio, 0.56; 95% CI, 0.33, 0.94) and in the combined outcome of short-term mortality and nonfatal reinfarction (odds ratio, 0.53; 95% CI, 0.35, 0.80) was observed in the trials comparing primary PTCA with thrombolytic therapy. In contrast, in trials in which an approach of thrombolysis and PTCA was compared with thrombolytic therapy alone, there was no important difference in early mortality, with an apparent reduction in mortality between 6 and 52 weeks. The lower mortality between 6 and 52 weeks among 6-week survivors seemed to be restricted to the subgroup of trials in which PTCA was used as a routine strategy (odds ratio, 0.58; 95% CI, 0.39, 0.87). CONCLUSIONS: Although the analyses of the various categories of trials suggest that primary PTCA may be more beneficial than thrombolytic therapy in AMI, these data should be interpreted cautiously unless confirmed by larger studies. In contrast, the addition of various other strategies of PTCA to thrombolytic therapy does not convincingly indicate a clinically different outcome than if a more conservative strategy is followed, in which PTCA is used only if clinically indicated. Some specific strategies, however, such as rescue PTCA in high-risk patients with occluded arteries, may be of benefit.     

Pharmacologic profile of survivors of acute myocardial infarction at United States academic hospitals

Optimal drug therapy for patients with acute myocardial infarction (AMI) is well described in the medical literature. However, data on the actual pharmacologic management of patients surviving AMI at academic hospitals is unavailable. The purpose of this study was to document treatment profiles in 500 patients surviving AMI at 12 academic hospitals in the United States. These profiles were compared with established guidelines and were evaluated for trends. Overall, thrombolytics (streptokinase > or = tissue-type plasminogen activator) were administered in 29% of the patients, with a greater proportion of patients receiving beta-blockers than calcium channel antagonists in the initial 72 hours (61% vs 40%; p < 0.005) and at discharge (51% vs 35%; p < 0.005). Further, women were less likely than men to receive thrombolytic therapy (odds ratio [OR] = 0.61; confidence interval [CI], 0.54 to 0.69) or beta-blocker therapy within the first 72 hours (OR = 0.61; CI, 0.55 to 0.67) or at hospital discharge (OR = 0.53; CI, 0.48 to 0.58). Overall, improvements could still be made in the number of patients who receive thrombolytic and acute and chronic beta-blocker therapies after AMI, particularly in women. Changes in treatment profiles may be a reflection of the publication of large clinical trials.     

Streptokinase-induced activation of the kallikrein-kinin system and of the contact phase in patients with acute myocardial infarction

Thrombolytic therapy in acute myocardial infarction (AMI) is hampered by a considerable reocclusion rate. Thrombin activity is enhanced, and contact-system activation via plasminemia might be possible. Prospectively we examined the contact phase and the kallikrein-kinin system and additional molecular markers of hemostasis and fibrinolysis in AMI. In 22 patients with AMI, blood sampling was performed at admission and < or =10 days afterward. Eleven patients received 1.5 Mio U streptokinase (group A) and were compared with 11 AMI patients without thrombolytic therapy (group B). All patients had systemic heparinization (5,000 IU bolus, i.v.; 1,000 IU/h, i.v.). In group A (vs. group B), the kallikrein-factor XII system was significantly activated (3 h after start of therapy): kallikrein activity 140 +/- 41 (vs. 43 +/- 8) U/L (p < 0.05); kallikrein inhibition 87 +/- 9 (vs. 113 +/- 7%; p < 0.05), and factor XII 70 +/- 14 (vs. 94 +/- 6%). C1 inhibitor and factor XII inhibition were decreased. High-molecular-weight kininogen consumption indicating bradykinin generation was enhanced (p < 0.01). In group A, thrombin activity (TAT) was increased, and a hypercoagulative state with increased fibrin degradation products (d-dimer) was found. Plasmin activation in group A was reflected by decreased plasminogen and antiplasmin levels (p < 0.01). The findings indicate that streptokinase induces activation of the contact phase-kinin system in vivo associated with a consecutive increase of thrombin and bradykinin generation. Activation of this pathway might substantially contribute to reocclusion after initially successful thrombolytic therapy and to hypotensive reactions observed after streptokinase.     

High level expression and structural characterisation of herpes simplex virus type I transcriptional activator VP16 (alpha-trans inducing factor)

BACKGROUND: Impaired platelet function has been reported in acute myocardial infarction (AMI) and stroke. However, prospective data on the changes of platelet status in patients before the occurrence of hemorrhagic stroke after thrombolytic therapy are unavailable. CASE DESCRIPTION: An 86-year-old male patient was among the 23 AMI patients enrolled in the platelet study for the GUSTO-III trial. He received 325 mg of aspirin daily for at least 6 years, suffered an AMI, and was successfully reperfused with alteplase, but after 44 hours developed a large hemorrhagic stroke resulting in paraplegia. Platelet aggregation and receptor expression were measured by flow cytometry and ELISA before thrombolysis and at 3, 6, 12, and 24 hours thereafter. The percentage of platelet aggregation was lower in the stroke patient at every time point when induced by 5 micromol/L of ADP, by 10 micromol/L of ADP, and by thrombin than in the rest of the AMI group. Ristocetin and collagen-induced aggregability were within the group range. Decreased platelet glycoprotein Ib, IIb, IIIa, and IIb/IIIa and vitronectin receptor expression were observed in the stroke patient. No other differences in p24 (CD9), very late antigen-2, P-selectin, and platelet/endothelial cell adhesion molecule-1 expression were determined. CONCLUSIONS: Profound depression of platelet status preceded the occurrence of hemorrhagic stroke in an elderly long-term aspirin user treated with thrombolytic therapy. Initial "exhausted" platelets may be responsible for the increased risk for hemorrhagic stroke after coronary thrombolysis.     

Metastatic carcinoma of the prostate mimicking primary carcinoid tumor of the lung and mediastinum

AIMS: To investigate the current use of thrombolytic therapy in the management of patients with acute myocardial infarction and to determine the potential for an increased use of thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: All hospitalised cases of acute myocardial infarction were identified in three health districts in the UK (population of 960,000) in patients under the age of 76 years during a 2-year period; 2439 patients had acute myocardial infarction, of whom 1264 (52%) received thrombolytic therapy. Failure to administer thrombolytic therapy was a result of the absence of diagnostic electrocardiograms in 712 (29.2%) patients, late presentation in 127 (5.2%), therapeutic error in 112 (4.6%), presence of a bleeding risk in 139 (5.7%) and other miscellaneous reasons in 80 (3.3%) patients. Thirty-eight of the 139 patients in whom bleeding risk was reported as a contra-indication could, in retrospect, have received thrombolytic therapy and a further 76 would have been suitable for primary PTCA. CONCLUSIONS: The potential for increasing the use of thrombolytic therapy seems to be limited and is unlikely to make a major impact on the in-hospital mortality from acute myocardial infarction. However, primary PTCA should be considered in those who are ineligible for thrombolysis because of bleeding risk as a contra-indication.     

Possibilities and limitations of thrombolysis. Benefits and risk in acute myocardial infarct, lung embolism, pelvic and leg vein thrombosis as well as cerebrovascular accidents

The indications for thrombolytic therapy in acute myocardial infarction, pulmonary embolism, deep venous thrombosis and ischemic stroke are reviewed on the basis of a risk-benefit analysis. There is strong evidence that thrombolysis benefits the majority of patients with acute myocardial infarction. Nevertheless, the overall proportion of patients actually receiving this therapy is disappointingly low (10-30%). Efforts are mainly required in minimizing delays in initiating thrombolysis (patient, doctor, in-hospital) and in providing thrombolytic therapy to an extended proportion of qualifying patients. This implies that many traditional but inappropriate exclusion criteria (e.g. age, presentation 6 to 12 hours after onset of symptoms, hypertension, reinfarction, brief cardiopulmonary resuscitation) are unfounded. Depending on duration of symptoms, infarct localization and age, we favor a differentiated thrombolytic regimen with rt-PA or streptokinase. In contrast to acute myocardial infarction, the risk-benefit ratio for the other thrombotic disorders discussed favours thrombolytic therapy only in a minority of carefully selected patients.     

Serial changes of plasma plasminogen activator inhibitor activity in acute myocardial infarction: difference between thrombolytic therapy and direct coronary angioplasty

The fibrinolytic system is impaired in patients with acute myocardial infarction (AMI). The primary regulatory element of fibrinolytic activity is plasminogen activator inhibitor (PAI). There are no reports, however, on the serial changes of PAI activity after thrombolysis or coronary angioplasty in patients with AMI undergoing emergency coronary angiography. This study was designed to examine the difference in the change of fibrinolytic activity between patients with AMI who underwent thrombolytic therapy with recombinant tissue-plasminogen activator (rTPA) and those who underwent direct percutaneous coronary angioplasty (PTCA). We measured the serial changes of PAI activity and tissue plasminogen activator (TPA) antigen after rTPA therapy or direct PTCA. Twenty-two patients received emergency coronary angiography and were treated with rTPA intravenously. Twenty patients underwent direct PTCA. Plasma PAI activity levels were increased on admission and further increased within 24 hours in patients treated with rTPA and in those treated with direct PTCA. In the thrombolysis group, there were two peaks in plasma PAI activity levels (IU/ml) at 4 hours (27.0 +/- 2.9) and at 16 hours (25.6 +/- 2.5) after the initiation of rTPA infusion. However, in the direct PTCA group, there was one peak of PAI activity (IU/ml) at 16 hours (23.9 +/- 2.7) after the initiation of direct PTCA. In conclusion, the PAI activity has two peaks in the thrombolysis group and one peak in the direct PTCA group.     

Analysis of creatine kinase, CK-MB, myoglobin, and troponin T time-activity curves for early assessment of coronary artery reperfusion after intravenous thrombolysis

BACKGROUND: Thrombolysis has become the standard therapeutic approach in patients with acute myocardial infarction. To identify patients who may benefit from early invasive procedures, reliable noninvasive assessment of success or failure of thrombolytic therapy is mandatory. METHODS AND RESULTS: In a prospective study in 63 consecutive patients undergoing thrombolysis for their first myocardial infarction, serial measurements of creatine kinase (CK), its isoenzyme CK-MB, myoglobin, and troponin T were done to determine their value for noninvasive prediction of coronary artery patency. Blood samples were drawn every 15 minutes during the first 90 minutes, every 30 minutes during the first 4 hours, every 4 hours during the first 24 hours, and every 8 hours during the first 72 hours. The perfusion status of the infarct-related artery was assessed angiographically 90 minutes after initiation of thrombolysis. For each marker, time to its peak concentration and its early initial slope (start of thrombolysis to 90 minutes thereafter) were determined. Areas under receiver operator characteristic (ROC) curves were 0.83, 0.76, 0.82, and 0.80 for maxima of CK, CK-MB, myoglobin, and troponin T, respectively (p = NS by univariate Z test). The corresponding values for early slopes of CK, CK-MB, myoglobin, and troponin T were 0.79, 0.82, 0.89, and 0.80 (p = 0.23 for comparison between myoglobin and CK-MB; p = 0.07 between myoglobin and CK). Sensitivity, specificity, and positive and negative predictive values regarding noninvasive prediction of coronary artery patency after 90 minutes were 80%, 82%, 95%, and 61% for time to CK maximum; 91%, 77%, 91%, and 77% for time to myoglobin maximum; 87%, 71%, 89%, and 67% for early CK slope; and 94%, 88%, 94%, and 82% for myoglobin slope, respectively. When myoglobin slope was assessed together with other clinical reperfusion markers (resolution of chest pain or ST segment elevation, occurrence of reperfusion arrhythmias) by logistic regression analysis, only the myoglobin slope was an independent predictor of coronary artery patency (p < 0.0001). CONCLUSIONS: With regard to noninvasive prediction of coronary artery patency after thrombolytic therapy, measurement of the early initial slopes of the serum markers within only 90 minutes after the initiation of therapy is as accurate as the determination of the time to their peak concentration. Compared with the other markers examined, myoglobin appears to have advantages because of its earlier rise, yielding a better negative predictive value and a higher area under the ROC curve for determination of its early initial slopes.     

Myoglobin concentration in serum as an early marker of reperfusion in patients with acute myocardial infarction after thrombolytic therapy

Detection of coronary artery reperfusion in patients after thrombolytic therapy because of acute myocardial infarction includes, except angiography, disappearance of anginal pain, regression of electrocardiographic and echocardiographic myocardial ischaemia symptoms, increased activity of creatine kinase (CPK) and its isoenzyme CK-MB. The aim of the study was to check whether changes in myoglobin serum concentration could be an early marker of coronary artery reperfusion after thrombolysis in patients with acute myocardial infarction. The studies comprised 50 patients treated by thrombolysis due to threatening myocardial infarction, including 29 men and 21 women aged 43-84 years. The patients were divided into 2 groups: the first (i)-patients without symptoms of coronary artery reperfusion and the second (ii)-those with symptoms of coronary artery reperfusion. It was assumed that the basis for successful reperfusion would be the reduction of total elevations of the ST segment 70% or more in electrocardiographic recording performed 3 hours after the start of thrombolytic treatment. Reperfusion was considered completely unsuccessful when reduction of total elevations was less than 30%. In patients with reperfusion after thrombolysis the concentrations of myoglobin were much higher and the activity of CPK and CK-MB significantly more intensive in comparison with patients without reperfusion symptoms in electrocardiographic assay. The evaluation of myoglobin concentration, CPK and CK-MB activity in the 3rd hour after the start of thrombolytic treatment in relation to maximum values is characterised by high sensitivity and specificity in the prediction of reperfusion onset Maximum myoglobin concentration in serum appears significantly earlier than maximum CPK and CK-MB activity and this marker is characterised by higher sensitivity and specificity in the evaluation of coronary artery reperfusion than the activity of CPK and CK-MB.     

Independent impact of thrombolytic therapy and vessel patency on left ventricular dilation after myocardial infarction. Serial echocardiographic follow-up

BACKGROUND: It has been shown that successful reperfusion of the infarct-related artery by thrombolysis can prevent left ventricular dilation after acute myocardial infarction; these beneficial effects were detected from several days to several months after infarction. To date, however, no study has shown that these effects can be demonstrated within hours after the onset of infarction. Furthermore, data are scarce on the independent impact of thrombolytic therapy and late vessel patency on ventricular volume and function. The aim of this study was to assess separate effects of thrombolysis and patency of the infarct-related artery on left ventricular size and function by serial two-dimensional echocardiographic examinations. METHODS AND RESULTS: We evaluated 131 consecutive patients with first acute myocardial infarction by two-dimensional echocardiography in the following sequence: days 1, 2, 3, 7, and after 3 and 6 weeks. Intravenous streptokinase was administered in 81 patients, and 50 patients were treated without thrombolysis. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were determined from apical two- and four-chamber views using the Simpson biplane formula and normalized to body surface area. Coronary angiography was performed in 107 patients after a mean of 26.0 +/- 20.2 (mean +/- SD) days after infarction. Patency of the infarct-related artery was assessed using TIMI criteria, with 54 considered patent (TIMI 3) and 53 with TIMI grade < 3. On day 1, end-systolic volume was significantly higher in patients not receiving thrombolysis (37.7 +/- 15.3 versus 33.0 +/- 10.6 mL/m2, P = .045). End-systolic volume (ESVi) was significantly higher in patients treated without thrombolysis throughout the study, whereas significant differences in end-diastolic volume (EDVi) were detected from day 3 (P = .041) onward and in ejection fraction (EF) from day 2 (P = .025) onward, all differences becoming progressively more significant with time (6-week values: EDVi, 78.8 +/- 25.4 versus 65.9 +/- 15.7 mL/m2, P = .001; ESVi, 45.4 +/- 22.6 versus 33.9 +/- 15.1 mL/m2, P = .002; EF, 45.1 +/- 11.6% versus 50.2 +/- 10.1%, P = .018). Patients with an occluded infarct-related artery (TIMI < 3) demonstrated highly significant differences at 6 weeks compared with patients with patent vessels (EDVi, 76.8 +/- 24.7 versus 65.2 +/- 15.6 mL/m2, P = .006; ESVi, 44.6 +/- 23.3 versus 31.9 +/- 12.2 mL/m2, P = .001; EF, 45.0 +/- 11.6% versus 52.1 +/- 9.0%, P < .001), but these differences developed more slowly than that seen among the thrombolytic subgroups. Indeed, multivariate analysis demonstrated that thrombolysis was the major determinant of initial volumes (P = .08, .02, and .08 for EDVi, ESVi, and EF, respectively), while vessel patency was the overwhelming determinant of subsequent changes (P = .0033, .0002, and .0024 for EDVi, ESVi, and EF, respectively). Additionally, ventricular volumes were significantly higher and ejection fractions lower in patients with anterior versus inferior infarction, but even adjusting for these differences as well as those associated with age, sex, and initial ventricular volume, the additive and independent impact of thrombolysis and infarct vessel patency persisted. CONCLUSIONS: These data indicate that the beneficial effect of thrombolysis on left ventricular size and function can be demonstrated in the earliest phases of acute myocardial infarction and that subsequent changes are mediated primarily through patency of the infarct-related artery. Thrombolytic therapy and late vessel patency thus have an additive and complementary impact in reducing ventricular dilation after myocardial infarction.     

Effect of the antitumor drug lonidamine on glucose metabolism of adriamycin-sensitive and -resistant human breast cancer cells

The efficacies of direct percutaneous transluminal coronary angioplasty (PTCA) and thrombolysis for the treatment of acute myocardial infarction were investigated in 80 patients treated within 12 hours of the onset of myocardial infarction by either PTCA (39 patients) or thrombolytic therapy (41 patients) followed by conservative care. The therapeutic approach was selected according to the treatment strategy at each of the 16 participating centers before the admission of the patients. The two treatment groups were closely matched in clinical characteristics except for the history of hypertension which occurred more in the thrombolysis group (22/39 vs 12/41, p = 0.026). The mean time before starting reperfusion therapy from the onset of symptoms was shorter in the thrombolysis group (2.3 +/- 1.5 vs 5.3 +/- 5.7 hours, p = 0.0001). Chest pain resolved more quickly in the PTCA group. Serial changes in the mean numbers of abnormal Q waves and mean values of the sum of elevated ST-segments on the electrocardiograms were similar in both groups. Serial changes of wall motion abnormality index on echocardiograms were similar in both groups. Coronary angiography after 4 weeks showed the thrombolysis group had greater residual luminal stenosis in the infarct-related artery. Left ventriculography after 4 weeks showed the PTCA group had better mean ejection fraction (68.1 +/- 11.2% vs 58.7 +/- 14.2%, p = 0.0263). Death (3/39 vs 1/41) and cardiac events (6/39 vs 6/41) after 4 weeks were similar in both groups. There was no significant difference in death and cardiac events between these two groups. However, the PTCA group had less severe residual luminal stenosis in the infarct-related artery and better left ventricular function after 4 weeks than the thrombolysis group.     

Effect on outcome of the presence or absence of chest pain at initiation of recombinant tissue plasminogen activator therapy in acute myocardial infarction. The Thrombolysis in Myocardial Infarction Investigators

To ascertain whether the outcome of patients with suspected myocardial infarction differs when chest pain is still present at initiation of thrombolytic therapy, participants in the Thrombolysis in Myocardial Infarction Phase II study, all of whom presented within 4 hours of symptoms onset, were retrospectively divided into 2 groups: (1) those with chest pain present at onset of intravenous thrombolysis, n = 3,000; and (2) those who were free of chest pain on beginning intravenous thrombolytic therapy, n = 337. Patients free of chest pain were older (58 vs 57 years, p = 0.01), more often women (23 vs 17%, p = 0.01), had fewer electrocardiographic leads with ST elevation (3.8 vs 4.1, p < 0.001), and the presenting event was confirmed less often as myocardial infarction than as chest pain without infarction (88 vs 96%, p < 0.001). There were no significant differences between the 2 groups for in-hospital death, reinfarction, recurrent ischemic events, stroke, overall hemorrhagic complications, coronary angioplasty or bypass surgery. At 6-weeks follow-up, more pain-free patients had resting ejection fraction > 0.55 (35 vs 31%, p = 0.001) and fewer developed congestive heart failure (12 vs 20%). At 1-year follow-up, fewer pain-free patients developed congestive heart failure (15 vs 21%, p = 0.009), but no differences existed between the 2 groups in frequency of death, reinfarction, coronary angioplasty, bypass surgery or anginal class. Thus, there are several observations in patients who were free of chest pain at onset of lytic therapy. (1) The majority developed enzymatic or electrocardiographic evidence of acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)