Treatment of reinfarction after thrombolytic therapy for acute myocardial infarction: an analysis of outcome and treatment choices in the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (gusto I) and assessment of the safety of a new thrombolytic (assent 2) studies.

BACKGROUND: Early reinfarction after thrombolytic therapy is associated with adverse outcomes and increased mortality. Among patients with reinfarction in the 1992 Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and the 1998 Assessment of the Safety of a New Thrombolytic (ASSENT 2) trials, we investigated temporal and regional differences in the use of repeat thrombolysis, revascularization (angioplasty and/or bypass surgery), or conservative measures and the outcomes of each management strategy. METHODS AND RESULTS: Data from the 4% of patients (n=2301) who experienced reinfarction after thrombolytic therapy were studied. Baseline characteristics, 30-day mortality, and incidence of total and hemorrhagic strokes were compared among the 3 treatment groups. The 30-day mortality did not differ between the repeat thrombolysis and revascularization groups (P=0.72), and it was significantly lower among patients treated by these 2 strategies than in those treated conservatively (11% and 11% versus 28%, respectively; P<0.001). Stroke rates did not differ significantly between the 3 treatment strategies (P=0.49). From 1992 to 1998, the percentage of reinfarction patients treated with repeat thrombolysis decreased from 29.3% to 18.5% in US centers and from 51.4% to 41.9% in all other centers (P<0.001). In contrast, use of revascularization procedures increased from 33.5% to 47.9% in US centers and from 8.1% to 23.0% in all other centers (P<0.001). CONCLUSIONS: Repeat thrombolysis and revascularization are associated with significantly lower mortality among reinfarction patients. Randomized trials are necessary to assess the exact risks and benefits of rethrombolysis versus interventional revascularization in this subset of high-risk patients presenting with reinfarction after thrombolytic therapy.

Early reinfarction after fibrinolysis: experience from the global utilization of streptokinase and tissue plasminogen activator (alteplase) for occluded coronary arteries (GUSTO I) and global use of strategies to open occluded coronary arteries (GUSTO III) trials.

BACKGROUND: Trials report a 2% to 6% incidence of reinfarction after fibrinolysis for acute myocardial infarction (MI). We combined the Global Utilization of Streptokinase and Tissue plasminogen activator (alteplase) for Occluded coronary arteries (GUSTO I) and Global Use of Strategies To Open occluded coronary arteries (GUSTO III) populations to better define frequency, timing, and clinical predictors of in-hospital reinfarction. METHODS AND RESULTS: In 55 911 patients with ST-segment elevation myocardial infarction (MI) who were receiving fibrinolysis, we compared baseline characteristics and mortality rate by reinfarction incidence and developed multivariable logistic regression models to predict in-hospital reinfarction and composite of death or reinfarction. Reinfarction occurred in 2258 patients (4.3%) a median of 3.8 days after fibrinolysis; rates did not differ between GUSTO I (4.0%) and GUSTO III (4.2%) or by fibrinolytic assignment (streptokinase, 4.1%; alteplase, 4.3%; reteplase, 4.5%; combined streptokinase and alteplase, 4.4%; P=0.55). Advanced age, shorter time to fibrinolysis, non-US enrollment, nonsmoking status, prior MI or angina, female sex, anterior MI, and lower systolic blood pressure were associated significantly with reinfarction. Patients with reinfarction had higher mortality at 30 days (11.3% versus 3.5% without reinfarction; odds ratio, 3.5; P<0.001) and from 30 days to 1 year (4.7% versus 3.2%; hazard ratio, 1.5; P<0.001). Significant multivariate predictors of in-hospital death or reinfarction included age, Killip class, systolic and diastolic blood pressures, heart rate, anterior MI, smoking status, prior MI, sex, and country of enrollment (all P<0.001). CONCLUSIONS: Reinfarction occurs infrequently after fibrinolysis but confers increased risk of 30-day and 1-year mortality. Some predictors of reinfarction differ from known predictors of death after MI. Improved treatment and prevention strategies for reinfarction deserve study.

Antecedent angina pectoris predicts worse outcome after myocardial infarction in patients receiving thrombolytic therapy: experience gleaned from the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

The significance of antecedent angina in predicting clinical outcome was assessed in 8,329 patients with acute myocardial infarction who received thrombolytic therapy with either recombinant tissue-type plasminogen activator or streptokinase. There were 2,370 patients with antecedent angina for greater than 1 month, 1,512 patients with antecedent angina for less than or equal to 1 month and 4,447 patients with no antecedent angina. The longer the duration of angina, the worse the baseline characteristics in the three groups: the mean patient age was 65 versus 62 versus 61 years, respectively (p less than 0.0001); the rate of previous myocardial infarction was 37% versus 18% versus 10% (p less than 0.0001); and the rate of hypertension was 40% versus 31% versus 27% (p less than 0.0001). Antecedent angina was associated with a longer hospital stay (11.3 and 11.7 days vs. 10.8 days, p less than 0.0001), a higher incidence of bypass surgery (2.2% vs. 1.2% vs. 0.7%, p = 0.0001), a worse Killip class at discharge (10.6% of patients in class greater than 1 vs. 8.7% vs. 6.4%, p = 0.0001), and a higher hospital and 6-month mortality (12.1% and 18% vs. 8.9% and 11.6% vs. 6.6% and 9.2%, respectively, p less than 0.0001). A multivariate analysis taking into account all baseline characteristics confirmed the independent association of antecedent angina with mortality, with a relative risk of 1.4 to 1.47 (p less than 0.001). Antecedent angina predicts a worse clinical outcome and a more intense use of medical resources in patients with acute myocardial infarction receiving thrombolytic therapy.

Coronary angioplasty under the prospective payment system: the need for a severity-adjusted payment scheme.

To evaluate the adequacy of Diagnosis Related Group prospective payment for percutaneous transluminal coronary angioplasty, the clinical characteristics, length of stay and hospital charges of all patients undergoing this procedure at Boston's Beth Israel Hospital during a 100 day period were examined. Of 113 such patients, the 61 patients in whom nonelective dilation was performed for unstable or postinfarction angina had a significantly greater length of stay and total hospital charge (10 +/- 6 days and $14,700 +/- $7,400, respectively) than did the 52 patients in whom elective dilation was performed (6 +/- 5 days and $8,500 +/- $7,700, respectively, p less than 0.0001). Under the current prospective payment system, however, these two groups of patients would have been placed in the same Diagnosis Related Group, and would have thus commanded equal institutional reimbursement. One potential revision of the payment system is presented to help to deal with this disparity.

Significance of diabetes mellitus in patients with acute myocardial infarction receiving thrombolytic therapy. Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

OBJECTIVES: The purpose of this study was to evaluate the risks and benefits associated with thrombolytic therapy in patients with diabetes presenting with acute myocardial infarction. BACKGROUND: Diabetes mellitus is associated with adverse risk factors and a hypercoagulable state that may adversely affect the outcome of thrombolytic therapy. METHODS: Data were analyzed from 8,055 of the 8,239 patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue Plasminogen Activator/Streptokinase Mortality trial (diabetes history was missing for 184 patients). RESULTS: There were 883 patients with and 8,272 patients without diabetes. Among the diabetic patients, 160 were receiving insulin therapy. Baseline risk factors were significantly worse in diabetic patients, who were older and had a higher rate of previous infarction and antecedent angina and a higher Killip grade at admission. Bleeding and hemorrhagic and ischemic stroke rates were similar among diabetic and nondiabetic patients. Hospital and 6-month mortality rates were highest among diabetic patients receiving insulin therapy (16.9% and 23.1%, respectively), followed by diabetic patients not receiving insulin therapy (11.8% and 17.8%), and lowest in nondiabetic patients (7.5% and 10.7%, p < 0.0001). Whereas diabetes of 5 years' duration was associated with a mortality rate similar to that of nondiabetic patients, a > 5-year duration was associated with a relative mortality risk of 1.38 (95% confidence interval [CI] 0.88 to 2.15) and a > 10-year duration with a relative mortality risk of 1.99 (95% CI 1.40 to 2.81). The independent relative risk for incremental mortality from discharge to 6 months was 1.74 (95% CI 1.21 to 2.50). Mortality rate among diabetic patients was lowest in patients who received both streptokinase and heparin (9.8% vs. 16.1% in patients who received streptokinase but no heparin, p < 0.05). CONCLUSIONS: The relative mortality of diabetic versus nondiabetic patients was similar to that observed in previous studies of patients with myocardial infarction not receiving thrombolytic therapy, indicating that mortality in diabetic patients receiving thrombolytic therapy is reduced to the same extent as in nondiabetic patients. In addition, risk of bleeding and stroke was not increased, indicating that diabetic patients can safely receive thrombolytic therapy for the same indications as nondiabetic patients.

Additional ST segment elevation during the first hour of thrombolytic therapy: an electrocardiographic sign predicting a favorable clinical outcome.

OBJECTIVES: The aim of this study was to investigate the significance of further ST elevation that occurs during the 1st h of thrombolytic therapy before the expected resolution. BACKGROUND: Early resolution of ST segment elevation is commonly accepted as a marker of clinical reperfusion during thrombolytic therapy for acute myocardial infarction. Using frequent electrocardiographic recordings, we observed in some patients further ST elevation that occurred during hour 1 of thrombolysis before the expected resolution. METHODS: To investigate the significance of this pattern, we classified 177 consecutive patients with a first acute myocardial infarction into two groups: Group A, 98 patients with ST elevation > or = 1 mm above the initial ST elevation during the 1st h of thrombolytic therapy, and Group B, 79 patients without this finding. RESULTS: Although the presence or absence of additional ST elevation was not associated with a clinical or prognostic difference in patients with a first inferior or posterior acute myocardial infarction, its presence indicated a more favorable clinical outcome and prognosis in patients with anterior infarction. Among the patients with anterior infarction the 65 patients in Group A had a higher ejection fraction (44 +/- 9% vs. 35 +/- 11%, p < 0.01), less heart failure (15% vs. 35%, p = 0.02) and a lower in-hospital mortality rate (0% vs. 8%, p = 0.04) than did the 37 patients from Group B. CONCLUSIONS: Additional ST elevation early during thrombolytic therapy in patients with anterior infarction suggests a favorable clinical outcome and thus may be indicative of successful reperfusion.

Prognostic significance of precordial ST segment depression on admission electrocardiogram in patients with inferior wall myocardial infarction.

OBJECTIVES: This study assessed retrospectively the correlation between the pattern of precordial ST segment depression on the admission electrocardiogram (ECG) and hospital mortality in patients with an inferior myocardial infarction treated with intravenous thrombolytic therapy. BACKGROUND: Previous studies have shown that in acute inferior myocardial infarction, ST segment depression in the precordial leads is associated with increased hospital mortality. However, the significance of the different patterns of precordial ST segment depression has been evaluated in only two previous studies. METHODS: The study included 1,321 patients (1,020 men) who enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial in Israel and received intravenous thrombolytic therapy. Patients with an ST segment elevation > or = 0.1 mV in at least two of the inferior leads were included. Patients were classified into four groups on the basis of their admission ECG: group I = patients with no precordial ST segment depression (n = 346); group II = those for whom the sum of ST segment depression in leads V1 to V3 was greater than that in leads V4 to V6 (n = 700); group III = those for whom the sum of ST depression in leads V1 to V3 was equal to that in leads V4 to V6 (n = 162); group IV = those with maximal ST depression in leads V4 to V6 (n = 113). RESULTS: The overall hospital mortality rate was 3.6% (48 patients): for groups I, II, III and IV it was 2.9%, 2.8%, 4.3% and 9.7%, respectively. Multivariable logistic regression analysis confirmed that hospital mortality was independently associated with the pattern of precordial ST segment depression. The odd ratios in group IV relative to group I was 2.78 (95% confidence interval 1.26 to 6.13, p = 0.007). CONCLUSIONS: The risk of mortality is higher in patients with an inferior myocardial infarction and maximal ST segment depression in precordial leads V4 to V6 versus precordial leads V1 to V3 on the admission ECG.

Comparative case fatality analysis of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial: variation by country beyond predictive profile. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

OBJECTIVES: This study was designed to examine the variation in mortality rates among countries participating in the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. BACKGROUND: Despite uniform inclusion and exclusion criteria and protocol in this trial, 30-day mortality rates (irrespective of treatment allocation) ranged from 4.2% to 14.8% among the participating countries. METHODS: With use of the risk factors identified by a multi-variate logistic model, the total study group was classified into deciles on the basis of each patient's risk profile and individual probability of dying within 30 days. Expected mortality rates were then calculated and compared with actual mortality for each decile of the total study group, as well as for patients from each country. RESULTS: Independent risk factors for mortality were older age (odds ratio 1.97 for each 10-year increment), systolic hypotension (blood pressure < 95 mm Hg) at entry (odds ratio 3.7), Killip class > 1 at entry (odds ratio 3.5), history of antecedent angina (odds ratio 1.23 to 1.49), history of diabetes mellitus (odds ratio 1.64), previous infarction (odds ratio 1.23) and history of never smoking (odds ratio 1.37). The overall mortality rate among the 1,612 patients in risk deciles 9 and 10 was 26%; for the 1,606 patients in deciles 1 and 2 it was 1.2%, with a sensitivity of 58.6% and a specificity of 83.7%. The logistic model closely predicted and explained the different mortality rates for most countries (the differences between expected and actual mortality were nonsignificant). However, in the total study group, the difference between the expected and actual mortality was significant (p < 0.001). This difference was mainly ascribed to the two countries with the highest and lowest mortality rates. When the patients from these two countries were excluded from the analysis, the overall difference became nonsignificant. CONCLUSIONS: These findings suggest that the recognized risk factors associated with increased case fatality in acute myocardial infarction account only in part for mortality differences across or within populations.

Prognostic significance of the admission electrocardiogram in acute myocardial infarction.

OBJECTIONS: We sought to access the ST segment and the terminal portion of the QRS complex in the initial electrocardiogram (ECG) as tools to predict outcome in patients with acute myocardial infarction given thrombolytic therapy. BACKGROUND: Previous studies assessing early risk stratification of patients with acute myocardial infarction by ECG criteria have focused on the number of leads with ST segment elevation or the absolute magnitude of ST deviation. A new classification independent of the absolute values of ST deviation was pursued. METHODS: Patients with ST elevation and positive T waves in at least two adjacent leads who received thrombolytic therapy were classified into two groups based on the absence (1,232 patients) or presence (1,371 patients) of distortion of the terminal portion of the QRS complex on the admission ECG. RESULTS: There were no differences between groups in the prevalence of previous angina, hypertension, current smoking, anterior infarction, time from onset of symptoms to therapy of type of thrombolytic regimen. Patients with QRS distortion were less likely to have had a previous infarction (12.0% vs. 18.4%, p = 0.02) or diabetes mellitus (16.9% vs. 21.4%, p = 0.003). They had higher peak creatine kinase levels (1,617 +/- 1,670 vs. 1,080 +/- 1,343 IU, p = 0.00001). Hospital mortality for those with and without QRS distortion was 6.8% and 3.8%, respectively (p = 0.0008). Multivariable logistic regression analysis confirmed that hospital mortality was independently associated with distortion of terminal portion of the QRS complex (odds ratio 1.78, 95% confidence interval 1.19 to 2.68, p = 0.004). CONCLUSIONS: Distortion of the terminal portion of the QRS complex on the admission ECG is independently associated with a higher hospital mortality rate in patients with acute myocardial infarction given thrombolytic therapy.

Diabetic retinopathy should not be a contraindication to thrombolytic therapy for acute myocardial infarction: review of ocular hemorrhage incidence and location in the GUSTO-I trial. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

OBJECTIVES: This study sought to evaluate the incidence of ocular hemorrhage in patients with and without diabetes after thrombolytic therapy for acute myocardial infarction. BACKGROUND: Ocular hemorrhage after thrombolysis has been reported rarely. However, there is concern that the risk is increased in patients with diabetes. In fact, diabetic hemorrhagic retinopathy has been identified as a contraindication to thrombolytic therapy without clear evidence that these patients have an increased risk for ocular hemorrhage. METHODS: We identified all suspected ocular hemorrhages from bleeding complications reported in patients enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I trial. Additional information was collected on a one-page data form. We compared the incidence and location of ocular hemorrhages in patients with and without diabetes. RESULTS: There were 40,899 patients (99.7%) with information about diabetic history and ocular bleeding. Twelve patients (0.03%) had an ocular hemorrhage. Intraocular hemorrhage was confirmed in only one patient. There were 6,011 patients (15%) with diabetes, of whom only 1 had an ocular hemorrhage (eyelid hematoma after a documented fall). The upper 95% confidence intervals for the incidence of intraocular hemorrhage in patients with and without diabetes were 0.05% and 0.006%, respectively. CONCLUSIONS: Ocular hemorrhage and, more important, intraocular hemorrhage after thrombolytic therapy for acute myocardial infarction is extremely uncommon. The calculated upper 95% confidence interval for the incidence of intraocular hemorrhage in patients with diabetes was only 0.05%. We conclude that diabetic retinopathy should not be considered a contraindication to thrombolysis in patients with an acute myocardial infarction.

Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) Steering Committee.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.

Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction: mechanism of the "smoker's paradox" from the GUSTO-I trial, with angiographic insights. Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: Our purpose was to evaluate the relation between smoking and the outcomes of patients receiving thrombolysis for acute myocardial infarction. BACKGROUND: A paradoxic beneficial effect has been observed in smokers with a myocardial infarction. We analyzed outcomes and baseline characteristics of 11,975 nonsmokers, 11,117 ex-smokers and 17,507 current smokers in a multinational trial of thrombolysis for acute myocardial infarction. METHODS: Patients were randomized to one of four thrombolytic protocols. An angiographic substudy in 2,431 patients evaluated reperfusion, reocclusion and ventricular function. Effects of smoking were evaluated by logistic regression analysis after adjustment for age and gender. A mortality model evaluated the simultaneous effect of baseline characteristics on the prognostic importance of smoking. These processes were performed with data from both the main trial and the angiographic substudy; then angiographic factors (coronary anatomy, patency and ejection fraction) were added to the model. RESULTS: Smokers were significantly younger by a mean of 11 years) and had less comorbidity or severe coronary artery disease than nonsmokers. Nonsmokers had significantly higher hospital and 30-day mortality rates (9.9% and 10.3%, respectively) than smokers (3.7% vs. 4%, respectively, both p < 0.001) and more in-hospital complications. The unadjusted odds ratio for 30-day mortality in nonsmokers was 3.36 (95% confidence interval [CI] 2.08 to 5.41), 1.21 (95% CI 0.71 to 2.08) after adjustment for age and gender and 1.08 (95% CI 0.59 to 1.96) after adjustment for all clinical baseline characteristics. CONCLUSIONS: Smokers receiving thrombolysis for acute myocardial infarction presented 11 years earlier than nonsmokers, which generally accounted for their better outcome. When other differences in clinical and angiographic baseline factors and therapeutic responses were evaluated, no significant difference in mortality was seen between smokers and nonsmokers.

Should thrombolytic therapy be administered in the mobile intensive care unit in patients with evolving myocardial infarction? A pilot study.

The growing recognition of the importance of early thrombolysis in evolving myocardial infarction was the basis for the present study, which evaluated the effectiveness, feasibility and safety of prehospital thrombolytic therapy. In a relatively small study, 118 patients were allocated to receive either prehospital treatment with recombinant tissue-type plasminogen activator (rt-PA) in the mobile intensive care unit (group A, 74 patients) or hospital treatment (group B, 44 patients). A total of 120 mg of rt-PA was infused over a period of 6 h. All patients were fully heparinized and underwent radionuclide left ventriculography and coronary angiography during hospitalization. Although group A was treated significantly earlier than group B after onset of symptoms (94 +/- 36 versus 137 +/- 45 min, respectively; p less than 0.001), no significant differences were observed between the groups in 1) extent of myocardial necrosis, 2) global left ventricular ejection fraction at discharge, 3) patency of infarct-related artery, 4) length of hospital stay, and 5) mortality at 60 days. However, a trend to a lower incidence of congestive heart failure at hospital discharge was observed in the prehospital-treated compared with the hospital-treated group (7% versus 16%, respectively; p = NS). No major complications occurred during transportation. It is concluded that myocardial infarction can be accurately diagnosed and thrombolytic therapy initiated relatively safely during the prehospital phase by the mobile intensive care team, thus instituting a beneficial clinical trend in favor of prehospital thrombolysis.

Repeat infusion of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction and early recurrent myocardial ischemia.

When conventional treatment of patients with early clinical reinfarction after thrombolytic therapy fails, mechanical revascularization may be attempted. An alternative strategy, repeat thrombolytic infusions, is reported. Fifty-two patients with acute myocardial infarction were treated with one or two additional thrombolytic infusions of recombinant tissue-type plasminogen activator (rt-PA) because of nonsustained ischemia after initial treatment with rt-PA or streptokinase. Thirty-five patients received the second infusion within 1 h of the first; 13 patients received the second infusion 1 to 72 h after the first and 4 patients received it later during their hospitalization. Bleeding complications occurred in 10 patients (19%); however, most of these were minor (no intracranial bleeding) and only 2 patients required blood transfusion. In 14 patients in whom the decrease in fibrinogen and plasminogen levels was measured after the first and second infusions, this decrease was only 25% and 63%, respectively--only slightly higher than the 22% and 53% decreases measured in 63 patients who had only one rt-PA infusion. In 44 patients (85%), the acute ischemia resolved completely within 1 h after initiation of the second infusion. In 23 patients (44%), pain and ST segment elevation did not recur and invasive coronary intervention was avoided. Thus, repeat rt-PA infusions can stabilize a substantial number of patients with acute reinfarction and, even when relief is temporary, repeat rt-PA infusions can minimize myocardial damage while patients await mechanical revascularization.

Outcome of thrombolytic therapy in relation to hospital size and invasive cardiac services. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

OBJECTIVE: The outcome of patients with acute myocardial infarction who received thrombolytic therapy was assessed in relation to the size and comprehensiveness of cardiovascular services in the admitting hospitals. METHODS: Two characteristics were obtained for each of the 438 hospitals: number of beds and in-house availability of cardiovascular services (coronary catheterization laboratory and coronary angioplasty or bypass surgery). Hospitals were grouped into four categories on the basis of size (< or = 300 vs > 300 beds) and availability of cardiovascular services. Baseline and outcome variables were compared by chi 2 analysis and logistic regression. Patients were followed up for 6 months. RESULTS: Baseline variables were comparable among hospital categories except for significant differences in the distribution of antecedent angina and time to treatment. Significantly more coronary angioplasties and bypass surgeries were performed in patients first treated in hospitals with coronary revascularization services (4.1% and 4.2% vs 1.0% and 1.9%, P < .0001). Rates of strokes (1.9% vs 1.3% and 1.6%, P = .54), hospital mortality (11.9% vs 8.5%, (P = .11), and 6-month mortality (17.0% vs 11.8% and 12.3%, P = .03) were highest among patients treated in small hospitals that had coronary revascularization facilities. The rate of invasive procedures was higher in the smaller hospitals (odds ratio [OR], 1.44; 95% confidence limits [CL], 1.11 and 1.87; P = .006) and in hospitals with coronary revascularization services (OR, 4.05; 95% CL, 3.14 and 5.22; P < .0001); hemorrhage was more frequent in centers with coronary revascularization facilities (OR, 1.39; 95% CL, 1.13 and 1.71; P = .002). Rates of hospital mortality and 6-month mortality were similar. CONCLUSIONS: Patients with acute myocardial infarction treated with thrombolytic therapy have the same mortality in small centers without in-house coronary revascularization services as in larger centers with such services.

An improved quantitative plaque assay for lymphocytes bearing antigen-specific cell receptors.

An improved method for the determination of the number of lymphoid cells bearing antigen-specific receptors is described. The method is based on the use of hapten-coupled bacteriophage (dinitrophenyl-T4) and detection of lytic plaques formed by the action of DNP-T4 on a target E. coli strain. The method is highly specific (up to 90% specific binding) and can be adapted for use with other antigenic determinants chemically attached to an active bacteriophage.

Admission clinical and electrocardiographic characteristics predicting in-hospital development of high-degree atrioventricular block in inferior wall acute myocardial infarction.

This study assessed the ability of simple clinical and electrocardiographic variables routinely obtained on admission to identify patients who are at high risk of developing high-degree atrioventricular (AV) block during hospitalization in 1,336 patients with inferior wall acute myocardial infarction (AMI). Patients were classified into 2 initial electrocardiographic patterns based on the J-point to R-wave amplitude ratio: pattern 1: those with J point/R wave <0.5 and pattern 2: patients with J point/R wave > or =0.5 in > or =2 leads of the inferior leads II, III, and aVF. High-degree AV block was found in 6.7% of patients (41 of 615) with pattern 1 versus 11.8% of the patients (85 of 721) with pattern 2 on admission electrocardiogram (p = 0.0008). Multivariate logistic regression analysis revealed that the only variables found to be independently associated with high-degree AV block were female gender (odds ratio [OR] 1.48; 95% confidence interval [CI] 0.98 to 2.23; p = 0.06); Killip class on admission > or =2 (OR 2.24; CI 1.43 to 3.51; p = 0.0004); initial electrocardiographic pattern 2 versus pattern 1 (OR 1.82; CI 1.22 to 2.21; p = 0.003); and absence of abnormal Q waves on admission (OR yes vs no 0.68; CI 0.44 to 1.05; p = 0.08). A simple electrocardiographic sign (J point/R wave > or =0.5 in > or =2 leads) is a reliable predictor of the development of advanced AV block among patients receiving thrombolytic therapy for inferior wall AMI.

Need for better severity indexes of acute myocardial infarction under diagnosis-related groups.

Clinical, demographic and administrative data, including length of stay and institutional charges, were examined for 219 patients hospitalized for acute myocardial infarction (AMI). Neither length of stay nor charges differed among AMI patients with or without cardiovascular complications as defined by Medicare's diagnosis-related group (DRG) categories (DRG 121 and 122, respectively) for patients who are discharged alive. Myocardial enzyme peak levels are the best predictors of hospital resource consumption for patients with AMI when considered alone or in combination with other factors. The "cardiovascular complications" designated by discharge diagnoses did not reflect resource consumption in our patient population. Sixteen percent of the patients studied underwent cardiac catheterization during hospitalization. These patients stayed in the hospital longer and incurred 70% higher charges; nevertheless, they were grouped with the remaining AMI patients in the current DRG formulation. Clinical evaluations such as cardiovascular complications are subject to interpretation, and are therefore less credible than enzyme measurements for recognizing the severity of a patient's AMI. Reimbursement based on objective measurements may avoid payment inequities.

Correlation of baseline plasminogen activator inhibitor activity with patency of the infarct artery after thrombolytic therapy in acute myocardial infarction.

Increased levels of plasminogen activator inhibitor (PAI) have recently been described in patients with acute myocardial infarction (AMI). To correlate PAI levels to patency of infarct arteries after thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA), 125 consecutive patients with AMI were examined. Blood levels of fibrinogen, plasminogen, tissue plasminogen activator (t-PA) and PAI were measured before treatment initiation, 10 minutes after completion of rt-PA infusion and 24 and 48 hours after treatment. Coronary angiography, performed in all patients 72 hours after beginning rt-PA infusion, revealed patent infarct arteries in 97 patients and occluded infarct arteries in 28 patients. Pretreatment levels of PAI were significantly higher in patients with occluded infarct arteries (18.0 +/- 11.5 vs 10.5 +/- 9.3 IU/ml, p less than 0.01). Conceivably, higher levels of PAI may interfere with the natural thrombolytic process and make pharmacologic thrombolytic intervention less effective.

Prognostic importance of delayed Q-wave evolution 3 to 24 hours after initiation of thrombolytic therapy for acute myocardial infarction.

The timing of Q-wave evolution and its prognostic significance was studied in 201 patients who received thrombolytic therapy for a first acute myocardial infarction (AMI). One hundred forty-one patients (70%) had evidence of a Q-wave AMI within 3 hours of the initiation of thrombolytic therapy, 31 (16%) developed Q waves after 3 hours but before hospital discharge, and 29 (14%) were discharged with a non-Q-wave AMI. Laboratory indicators of myocardial damage and in-hospital morbidity and mortality were greater among patients with Q-wave AMIs than with non-Q-wave AMIs. When these indexes were examined with respect to the timing of Q-wave evolution, the prognosis of patients with delayed Q-wave development was similar to that of patients with non-Q-wave AMIs. Thus, compared to patients with early (less than or equal to 3 hours) Q-wave evolution, patients with delayed Q-wave evolution or with a non-Q-wave AMI had a smaller creatine kinase peak (mean 661 to 1,081 vs 1,251 to 1,541 IU; p = 0.005), better preservation of left ventricular function as measured by radionuclide ventriculography before discharge (mean +/- standard deviation 54 +/- 11% vs 47 +/- 13%; p less than 0.01), and a lower incidence of congestive heart failure at discharge (3 vs 15%; p = 0.02). In-hospital mortality was lower among patients with delayed Q-wave evolution or with a non-Q-wave AMI (5 of 141 vs 0 of 60; difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)