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Objectives: We sought to determine whether the prehospital electrocardiogram (ECG) improves the diagnosis of an acute coronary syndrome., Background: The ECG is the most widely used screening test for evaluating patients with chest pain., Methods: Prehospital and in-hospital ECGs were obtained in 3,027 consecutive patients with symptoms of suspected acute myocardial infarction, 362 of whom were randomized to prehospital versus hospital thrombolysis and 2,665 of whom did not participate in the randomized trial. Prehospital and hospital records were abstracted for clinical characteristics and diagnostic outcome., Results: ST segment and T and Q wave abnormalities suggestive of myocardial ischemia or infarction were more common on both the prehospital and hospital ECGs of patients with as compared with those without acute coronary syndromes (p < or = 0.00001). Those with prehospital thrombolysis were more likely to show resolution of ST segment elevation by the time of hospital admission (14% vs. 5% in patients treated in the hospital, p = 0.004). In patients not considered for prehospital thrombolysis, both persistent and transient ST segment and T or Q wave abnormalities discriminated those with from those without acute coronary ischemia or infarction. Compared with ST segment elevation on a single ECG, added consideration of dynamic changes in ST segment elevation between serial ECGs improved the sensitivity for an acute coronary syndrome from 34% to 46% and reduced specificity from 96% to 93% (both p < 0.00004). Overall, compared with abnormalities observed on a single ECG, consideration of serial evolution in ST segment, T or Q wave or left bundle branch block (LBBB) abnormalities between the prehospital and initial hospital ECG improved the diagnostic sensitivity for an acute coronary syndrome from 80% to 87%, with a fall in specificity from 60% to 50% (both p < 0.000006)., Conclusions: ECG abnormalities are an early manifestation of acute coronary syndromes and can be identified by the prehospital ECG. Compared with a single ECG, the additional effect of evolving ST segment, T or Q waves or LBBB between serially obtained prehospital and hospital ECGs enhanced the diagnosis of acute coronary syndromes, but with a fall in specificity.

Physicians and other health care professionals play an important role in reducing the delay to treatment in patients who have an evolving acute myocardial infarction. A multidisciplinary working group has been convened by the National Heart Attack Alert Program (which is coordinated by the National Heart, Lung, and Blood Institute of the National Institutes of Health) to address this concern. The working group's recommendations target specific groups of patients: those who are known to have coronary heart disease, atherosclerotic disease of the aorta or peripheral arteries, or cerebrovascular disease. The risk for acute myocardial infarction or death in such patients is five to seven times greater than that in the general population. The working group recommends that these high-risk patients be clearly informed about symptoms that they might have during a coronary occlusion, steps that they should take, the importance of contacting emergency medical services, the need to report to an appropriate facility quickly, treatment options that are available if they present early, and rewards of early treatment in terms of improved quality of life. These instructions should be reviewed frequently and reinforced with appropriate written material, and patients should be encouraged to have a plan and to rehearse it periodically. Because of the important role of the bystander in increasing or decreasing delay to treatment, family members and significant others should be included in all instruction. Finally, physicians' offices and clinics should devise systems to quickly assess patients who telephone or present with symptoms of a possible acute myocardial infarction.

Objectives: The aim of this study was to determine whether streptokinase treatment improves long-term survival in patients with acute myocardial infarction., Background: Thrombolytic treatment for acute myocardial infarction reduces early mortality and improves the 1-year survival rate, but the long-term (3 to 8 years) survival benefits of treatment and the relation between survival and baseline clinical characteristics, infarct size and ventricular function have not been established., Methods: We assessed survival status at a minimum of 3 and a mean of 4.9 +/- 2.3 years in 618 patients randomized between 1981 and 1986 to receive conventional treatment (n = 293) or thrombolysis with streptokinase (n = 325) in the Western Washington Intracoronary (n = 250) and Intravenous (n = 368) Streptokinase in Myocardial Infarction trials. The relation between long-term survival and thrombolytic treatment, admission baseline clinical characteristics and late radionuclide tomographic thallium-201 infarct size and ejection fraction was assessed in a subset of patients., Results: Survival at 6 weeks was 94% in patients who received streptokinase versus 88% in the control group (p = 0.01). However, survival at 3 years was 84% in the streptokinase group and 82% in the control group and for the total period of follow-up, there was no significant survival benefit (p = 0.16). Analysis by infarct location showed a higher survival rate at 3 years for patients treated with anterior infarction (76% vs. 67% for the control group), but no overall survival benefit (p = 0.14). Survival at 3 years for patients with an inferior infarction was 89% in the streptokinase group and 91% in the control group (p = 0.62). By stepwise Cox regression analysis, admission clinical variables associated with decreased long-term survival were anterior infarction, advanced age, history of prior infarction and the presence of pulmonary edema or hypotension. Although streptokinase therapy was associated with improved survival, it was not an independent determinant of survival (p = 0.069). Ejection fraction and thallium-201 infarct size measured approximately 8 weeks after enrollment had a strong association with long-term survival. Univariate analysis in a subgroup of 289 patients with complete data selected infarct size, ejection fraction, age and history of prior infarction as predictors of survival. In the multivariate model, only ejection fraction (p < 0.0001), age (p = 0.008) and prior myocardial infarction (p = 0.02) remained strong predictors., Conclusions: In these early trials of thrombolytic therapy for acute myocardial infarction, streptokinase improved early survival, but there was little long-term survival benefit. This failure to show an improvement in the 3- to 8-year survival rate may also reflect the need to study a larger group of patients or to initiate treatment earlier after symptom onset.

Background: The Coronary Artery Surgery Study (CASS) Registry is used to evaluate the effect of various baseline clinical and angiographic factors on mortality after acute out-of-hospital myocardial infarction (MI) in patients with and without prior coronary bypass surgery., Methods and Results: Among the CASS Registry patients, there were 985 medical and 369 surgical patients who had an MI out of the hospital within 3 years after enrollment. In the medical group, 20% died before hospitalization. Medical patients with baseline three-vessel disease or left ventricular (LV) dysfunction were at high risk of immediate death. For medical patients who were hospitalized with MI, mortality was higher for older patients and those with severe angina as well as for those with extensive disease and LV dysfunction. The total 30-day mortality for medical patients was 36%. In the surgical group, 12% died before hospitalization. Surgical patients with LV dysfunction or prior MI were at highest risk of immediate death. For surgical patients hospitalized with MI, mortality was significantly increased only for patients with baseline LV dysfunction. Mortality was not significantly higher for surgical patients with multivessel disease. The total 30-day mortality for surgical patients was 21%. The prior use of aspirin or beta-blockers was not associated with reduced mortality from subsequent MI for either medical or surgical patients. Although the prevalence of cigarette smoking was high among patients who had an MI, cigarette smoking did not alter the infarct-related mortality rate., Conclusions: The surgical group had lower mortality rates than the medical group both immediately (p = 0.001), after hospitalization (p less than 0.0001), and at 30 days (p less than 0.0001).

The findings in 3,256 consecutive patients hospitalized for acute myocardial infarction were tabulated to assess the history, treatments and outcome in the elderly; 1,848 patients (56%) were greater than 65 years of age, including 28% who were aged greater than or equal to 75 years. The incidence of prior angina, hypertension and heart failure (only 3% of patients less than 55 years of age had a history of heart failure compared with 24% greater than or equal to 75 years old) was found to increase with age. Twenty-nine percent of patients less than 75 years of age were treated with a systemic thrombolytic drug compared with only 5% of patients older than 75 years. Mortality rates increased strikingly with advanced age (less than 2% in patients less than or equal to 55, 4.6% in those 55 to 64, 12.3% in those 65 to 74 and 17.8% in those greater than or equal to 75 years). Both the incidence of complicating illness and a nondiagnostic electrocardiogram (ECG) increased with age. In a multivariate analysis of outcome in older patients (greater than or equal to 65 years), adverse events were related to both prior history of heart failure (odds ratio 3.9) and increasing age (odds ratio 1.4 per each decade of age). Outcome was not improved by treatment with thrombolytic drugs, but these agents were prescribed to only 12% of patients greater than 65 years of age, thereby reducing the power for detecting such an effect.(ABSTRACT TRUNCATED AT 250 WORDS)

A prehospital computer-interpreted electrocardiogram (ECG) was obtained in 1,189 patients with chest pain of suspected cardiac origin during an ongoing trial of prehospital thrombolytic therapy in acute myocardial infarction. Electrocardiograms were performed by paramedics 1.5 +/- 1.2 h after the onset of symptoms. Of 391 patients with evidence of acute myocardial infarction, 202 (52%) were identified as having ST segment elevation (acute injury) by the computer-interpreted ECG compared with 259 (66%) by an electrocardiographer (p less than 0.001). Of 798 patients with chest pain but no infarction, 785 (98%) were appropriately excluded by computer compared with 757 (95%) by an electrocardiographer (p less than 0.001). The positive predictive value of the computer- and physician-interpreted ECG was, respectively, 94% and 86% and the negative predictive value was 81% and 85%. Prehospital screening of possible candidates for thrombolytic therapy with the aid of a computerized ECG is feasible, highly specific and with further enhancement can speed the care of all patients with acute myocardial infarction.

Since 1988, 641 black and 11,892 white patients with chest pain of presumed cardiac origin have been admitted to coronary care units in 19 hospitals in metropolitan Seattle. Black men and women were younger (58 vs 66, p less than 0.0001), more often admitted to central city hospitals (p less than 0.0001), and developed evidence of acute myocardial infarction (AMI) less often (19 vs 23%, p = 0.01). In the subset of 2,870 AMI patients, blacks (n = 121) were younger (59 vs 67, p less than 0.0001) and had less prior coronary artery bypass graft surgery (2 vs 10%, p = 0.005) and more prior hypertension (67 vs 46%, p less than 0.0001). During hospitalization, whites (n = 2,749) had higher rates of coronary angioplasty (18 vs 10%, p = 0.03) and coronary artery bypass graft surgery (10 vs 4%, p = 0.04), although thrombolytic therapy and cardiac catheterization were used equally in the 2 groups. Hospital mortality was 7.4% for black and 13.1% for white patients (p = 0.07). However, after adjustment for key demographic and clinical variables by logistic regression, this difference was not as apparent (p = 0.38). Questions about the premature onset of coronary artery disease, excess systemic hypertension, and the differential use of interventions in black persons have been raised by other investigators. Despite differences in age, referral patterns and the use of coronary angioplasty and bypass surgery, black and white patients with AMI in metropolitan Seattle had similar outcomes.

This study comprised a registry and an emergency department treatment trial using recombinant tissue plasminogen activator. During 1 year, 1,028 patients with documented acute myocardial infarction (AMI) were evaluated for eligibility for thrombolytic therapy. Of these, 221 patients (22%) were eligible for thrombolytic therapy under currently accepted criteria, 175 (79%) of them were correctly identified by emergency department physicians for thrombolytic therapy, and 160 were enrolled in the trial. Only 3 patients (2%) enrolled by emergency department physicians did not subsequently evolve documented AMI. In all, 807 patients (78%) were ineligible for thrombolytic therapy: 335 (33%) because of greater than or equal to 1 contraindications, 364 (36%) because of nondiagnostic electrocardiograms on presentation, and 105 (10%) because of age greater than 75 years, or greater than 6 hours of chest pain at presentation, or both. Mortality in treated patients at 14 days was 5.6%, and survival at 1 year was 92%. The mean time from hospital arrival to thrombolytic treatment was 55 +/- 27 minutes. Initial management of AMI with recombinant tissue plasminogen activator in the emergency department provided rapid and safe treatment comparable to that reported in trials that started treatment in the coronary care unit. The proportions of eligible patients could be increased from 1 in 5 to 1 in 3, if patients currently excluded only because of age greater than 75 years or because of greater than 6 hours of chest pain were offered treatment.

Several large trials of thrombolytic therapy have shown that treatment initiated in the first 1 or 2 hours following the onset of symptoms of acute myocardial infarction (AMI) is more effective than therapy started later in the course of illness. From our experience in three thrombolytic trials we concluded it would be difficult to reduce the total time from symptom onset to therapy without a major change in patient management. To accomplish this goal we have initiated MITI (Myocardial Infarction Triage and Intervention Project), a program for the prehospital diagnosis of AMI using specially trained paramedics, a checklist to establish eligibility for and contraindications to thrombolytic therapy, and a portable, battery-powered 12-lead electrocardiography (ECG) cellular telephone system that allows an electrocardiographic diagnosis to be made remotely by an emergency department physician. In the feasibility phase of MITI, 2,472 patients with chest pain of presumed cardiac origin were evaluated; 677 (27%) met the rigorous history and physical exam inclusion and exclusion criteria for potential thrombolytic therapy and had an ECG performed in the field. Of these ECGs, 522 were transmitted successfully by cellular telephone to a base station physician. Of the 522 patients, 107 had ST-segment elevation and met our criteria for initiation of thrombolytic therapy. Of the 2,472 patients with chest pain evaluated by the emergency medical technicians, 453 (18%) were diagnosed with AMI during hospitalization. Of these AMI patients, only 105 (23%) met the clinical examination and ECG criteria for pre-hospital thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

In 92 acute myocardial infarction (AMI) patients treated with tissue plasminogen activator 2.3 +/- 1.2 hours after the onset of chest pain, echocardiography was performed at 11 +/- 14 hours (early) and, in 49 patients, again at 13 +/- 7 weeks (late). Infarct location and the left ventricular wall motion score index--the average score (normal = 1, hypokinetic = 2, akinetic = 3, dyskinetic = 4) for 20 segments--were determined by 2 observers unaware of clinical, angiographic or electrocardiographic data. Concordance between noninvasive infarct location by electrocardiography or echocardiography and infarct-related artery at angiography 4 +/- 2 days later (n = 85) was 76 and 81%, respectively. The early wall motion score index was worse for anterior (1.8 +/- 0.4) versus inferior (1.3 +/- 0.2, p less than 0.0001) or posterior-lateral (1.6 +/- 0.2, p = 0.0003) infarcts. Overall, the wall motion score index improved from early to late echocardiography (n = 49, 1.5 +/- 0.3 to 1.3 +/- 0.3, p = 0.0008). However, improvement was confined to those with time to treatment less than or equal to 2 hours (n = 22, 1.4 +/- 0.3 to 1.2 +/- 0.2, p less than 0.0001), and evidence of reperfusion at angiography (n = 38, 1.5 +/- 0.3 to 1.2 +/- 0.3, p less than 0.0001). The decrease in the wall motion score index was related to a decrease in the number of adjacent involved segments (5.5 +/- 3.0 to 3.7 +/- 3.9/patient, p = 0.0006). Thus, echocardiography early after AMI identifies infarct location. Improvement in regional wall motion is seen after early treatment with intravenous tissue plasminogen activator.

It is now clear that intravenous thrombolytic therapy is the treatment of choice in selected patients with AMI. It is most effective in patients with their first MIs and of greatest benefit, at least in the short term, for those with large infarctions. It should be given within the first three hours to be most effective and there probably is little benefit for patients after 5-6 hours unless there is evidence of ongoing ischemia. Patients must be selected carefully to reduce the likelihood of serious complications, including intracerebral hemorrhage. There is, as yet, no convincing evidence that early intervention with PTCA or surgery can improve the outcome of patients who have received initial early intravenous thrombolytic therapy when they develop recurrent myocardial ischemia (21,22). The use of rt-PA probably is preferable to the use of streptokinase, but further experience is needed before this can be determined with certainty. The large difference in the cost of these agents will need to be evaluated by the medical community and other health care providers who finally will determine the pattern of use of these and future thrombolytic agents.

After cardiac catheterization and coronary arteriography, 134 patients who had had an acute myocardial infarction were randomly assigned to treatment with intracoronary streptokinase (4000 U per minute, begun approximately 4 1/2 hours after the onset of symptoms, for a total of 286,000 +/- 77,800 U over 72 +/- 24 minutes); 116 control patients received standard care after they returned to the coronary care unit, immediately after angiography. Preliminary results of this trial have been published in the Journal (1983; 309:1477-81). During the first 30 days, 5 deaths occurred in the streptokinase group and 13 occurred in the control group (3.7 vs 11.2 per cent, P = 0.02); during the first year, the corresponding figures were 11 and 17 deaths (8.2 vs. 14.7 per cent, P = 0.10). However, when a minor imbalance in the ejection fraction and infarct location between the two groups was adjusted by logistic regression, the difference in one-year mortality became significant (P = 0.03). In the streptokinase group, 2 of the 80 patients in whom perfusion was reestablished (2.5 per cent) had died by one year, whereas 3 of the 13 with partial reperfusion (23.1 per cent) and 6 of the 41 with no reperfusion (14.6 per cent) had died (P = 0.008). Mortality among patients with partial reperfusion was not significantly different from that among those without reperfusion (P greater than 0.90). No base-line clinical, angiographic, or hemodynamic variable was predictive of successful reperfusion, according to univariate and multivariate analyses. We conclude that intracoronary streptokinase reduces one-year mortality among patients with acute myocardial infarction, but this improvement occurs only among those in whom thrombolysis results in coronary artery reperfusion.

Intracoronary streptokinase (STK) was given to 52 patients and 2 million U of intravenous urokinase was given to 15 patients with acute myocardial infarction less than 3 hr from onset of symptoms. Wall motion in the infarct region improved in 20 patients receiving STK alone (-2.5 +/- 1 to 2.1 +/- 1.1 SD/chord) and in 22 patients receiving STK and undergoing coronary bypass surgery within 24 hr (-2.5 +/- 1 to -1.5 +/- 1.0 SD/chord). Wall motion was unchanged in 10 patients not successfully reperfused with STK (-2.9 +/- 0.7 to -3.1 +/- 0.7 SD/chord). Regional wall motion improved at least 1.0 SD/chord in 71% of 14 patients treated within 2 hr of onset of symptoms, but in only 29% of 34 treated after 2 hr. Mean coronary artery stenosis after thrombolysis was 77 +/- 9%. Rethrombosis was associated with a stenotic cross-sectional area of less than 0.4 mm2. Ventricular function did not improve, with a residual stenosis of 0.4 mm or less in diameter. The Western Washington randomized trial reported a 1 year mortality of 2.5% in 80 successfully reperfused patients, but a mortality of 23% in 13 in whom reperfusion was partial and of 14.6% in 41 in whom reperfusion failed. The improved survival with successful reperfusion and improved ventricular performance with early and more complete reperfusion has stimulated interest in the need for angioplasty and coronary artery bypass grafting after thrombolytic therapy.

In the 3 Western Washington thrombolytic therapy trials, 54.9% of patients with acute myocardial infarction arrived at the hospital within 2 hours of symptom onset. These early arrivers were younger and more likely to be hypotensive and in cardiogenic shock than were patients arriving later. There were decreases in the time from symptom onset to hospital arrival (p = 0.0002) and in the time from hospital arrival to institution of thrombolytic therapy (p less than 0.0001) in the 8 hospitals that participated in both the Western Washington intravenous streptokinase and tissue plasminogen activator trials from 1983 to 1988. For those patients receiving thrombolysis, early arrival was associated with increased survival (p = 0.031) after adjustment by Cox regression analysis for important clinical predictors of long-term survival. These covariates included pulmonary edema, anterior wall acute myocardial infarction, hypotension and absence of chest pain at hospital arrival. Reductions in barriers to timely administration of thrombolytic therapy can be achieved and can result in improved survival.

The relationships among clinical variables, coronary anatomy, and left ventricular function during the early hours of acute myocardial infarction (AMI) were evaluated from data acquired in the Western Washington Intracoronary Streptokinase Trial. All patients had symptoms and electrocardiographic changes typical of AMI. All data were obtained before treatment with streptokinase. Mean time to catheterization was 4.1 hr after onset of symptoms. Coronary angiograms (n = 245) were analyzed for location of infarct-related occlusion and collateral flow to the infarct bed. Left ventricular ejection fraction and regional left ventricular function were quantitated in 227. Sixty-two percent of occlusions were in the most proximal segment of the involved coronary artery. Collateral circulation was seen in 42% overall, in 31% with left anterior descending artery (LAD) occlusion, and in 52% with right coronary artery (RCA) occlusion (p less than .005). Left ventricular ejection fraction was lowest and regional function was most abnormal in the group with proximal LAD occlusion. Hyperkinesis was present in 32%; in those with hyperkinesis, hyperkinetic segment length was longest in those with RCA or circumflex occlusion. Multivariate analysis identified proximal LAD occlusion as the factor most closely associated with left ventricular ejection fraction and with measures of left ventricular regional hypofunction. We conclude that (1) AMI is usually caused by occlusion or subtotal occlusion in the most proximal portion of the involved coronary artery, (2) collateral circulation is more frequent with RCA than with LAD occlusion, and (3) location of the infarct-related occlusion is the most important determinant of global and regional left ventricular function in the early hours of AMI.

The Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial enrolled 250 patients with acute myocardial infarction. After the coronary angiographic diagnosis of thrombosis, patients were randomly assigned to receive either conventional therapy with heparin or intracoronary streptokinase followed by heparin. Of the 232 patients who survived at least 60 days, 207 (89%) underwent radionuclide ventriculographic determination of global and regional ejection fraction at a single institution at 62 +/- 35 days after infarction. In the first 100 patients, infarct size was also determined by quantitative single-photon emission tomographic imaging with thallium-201 (201Tl) and expressed as a percentage of the left ventricle with a perfusion defect. Overall, global ejection fraction did not differ between patients treated with streptokinase (45.9 +/- 13.9%; n = 115) and control patients (46.1 +/- 14.4%; n = 92, p = NS). Similarly, the regional posterolateral, inferior, and anteroseptal ejection fraction did not differ between the two groups. Infarct size as measured by 201Tl tomography was 19.4 +/- 12.8% (n = 52) of the left ventricle for the streptokinase group and 19.6 +/- 11.8% (n = 48; p = NS) for the control group. When patients were compared within groups by electrocardiographic location of infarction, time to treatment, or the presence or absence of vessel opening, there were no significant differences between streptokinase and control patients. Statistical inclusion of the 18 patients who died early and were unavailable for study also failed to modify the results, except for a possible reduction in inferior infarct size as measured by 201Tl tomography.(ABSTRACT TRUNCATED AT 250 WORDS)

The Society for Cardiac Angiography maintains a registry of intracoronary streptokinase therapy (IC-SK) in patients with acute myocardial infarction. Between July 1981 and August 1984, 1,029 patients were entered into the registry. The baseline and clinical characteristics of patients were determined, the early results of therapy were evaluated, and baseline characteristics of those in whom reperfusion was achieved were compared with those in whom it was not. Multivariate discriminant analysis was used to identify the predictors of reperfusion and hospital mortality. The overall rate of reperfusion was 71.2%. Reperfusion was positively associated with hypotension, absence of cardiogenic shock and early treatment. The hospital mortality rate for all patients was 8.2% and was higher for women and the elderly. The hospital mortality was significantly lower among patients in whom reperfusion was achieved compared with those in whom it was not (5.5% vs 14.7%, p less than 0.0001) and for several high-risk subgroups. Thus, coronary artery reperfusion induced by IC-SK significantly reduces hospital mortality in high-risk patients with acute myocardial infarction. High-risk patients in whom reperfusion fails with IC-SK therapy should be considered for early coronary angioplasty or coronary artery bypass surgery.

To determine whether intracoronary streptokinase improves late regional wall motion or reduces left ventricular aneurysm or thrombus formation in patients with acute myocardial infarction, two-dimensional echocardiography was performed at 8 +/- 3 weeks after infarction in 83 patients randomized to streptokinase (n = 45) or standard therapy (n = 38) in the Western Washington Intracoronary Streptokinase Trial. Among the patients treated with streptokinase, the average time to treatment was 4.7 +/- 2.5 hours after the onset of chest pain, and 67% had successful reperfusion. Regional wall motion was assessed in nine left ventricular segments on a scale of 1 to 4 (normal, hypokinetic, akinetic and dyskinetic). Left ventricular thrombus formation was interpreted as positive, equivocal or negative. All patients received anticoagulant therapy in the hospital and 52 received such therapy after hospital discharge. The mean (+/- SD) global (1.5 +/- 0.4 in both groups) and regional wall motion scores in the streptokinase-treated and control groups were not significantly different. The prevalence of aneurysm was 16% in both groups. Left ventricular thrombus was identified in only five patients (positive identification in four, and equivocal in one), all in the streptokinase-treated group (p = NS). There were also no differences between streptokinase and control treatment in any of the echocardiographic variables in subgroups of patients with anterior infarction, inferior infarction, no prior infarction or reperfusion with streptokinase. It is concluded that intracoronary streptokinase given relatively late in the course of acute myocardial infarction does not result in improved global or regional wall motion or a reduction in left ventricular thrombus or aneurysm formation in survivors studied 2 months after myocardial infarction.

Seven hundred ninety-three patients had coronary artery bypass graft (CABG) surgery within 30 days after acute myocardial infarction (AMI) between August 1982 and July 1987. Hospital mortality was 5.7%. Age, surgical priority, prior CABG surgery, congestive heart failure (CHF), and type of AMI were associated with increased hospital mortality by logistic regression analysis of nine independent variables. When the analysis was carried out separately for men and women, the same predictive variables were identified for men, but only surgical priority and age were predictive of operative mortality for women. Elective CABG surgery can be carried out at low risk following AMI in stable patients regardless of the interval between AMI and surgery. Patients who undergo urgent or emergency surgery and those who have CHF, Q wave infarction, or a history of prior AMI are at increased risk.

We evaluated the relationship between baseline factors defined at 4.6 +/- 2.1 hr after onset of acute myocardial infarction and 1 year survival in 245 patients entered in the Western Washington Intracoronary Streptokinase Trial. Univariate statistics identified a significant relationship between 10 of these factors and survival. Multivariate analysis identified three factors as being most closely related to survival: (1) left ventricular ejection fraction (LVEF) (p less than .0001), (2) treatment with streptokinase (p = .03), and (3) location of infarction (p = .04). Mathematic models based on this analysis and applied to our patients identified high- and low-risk subgroups for 1 year mortality. Patients receiving standard, not interventional, therapy with anterior infarction and an LVEF of 50% or less and those with inferior infarction and an LVEF of 39% or less comprised the high-risk group. For patients receiving standard therapy, 1 year mortality was 41% in the high-risk group and 4% in the low-risk group. The models illustrated the magnitude of benefit of streptokinase treatment and achievement of complete reperfusion for those at low and high risk. We conclude that LVEF determined in the first hours of acute myocardial infarction is the most important of all baseline factors for prediction of 1 year survival. Mathematic models based on left ventricular function measured as ejection fraction are useful for risk stratification in this setting.

A randomized trial of intracoronary thrombolysis in a multicenter, geographically limited community has been undertaken. There have been no deaths or important morbidity because of heart catheterization. Preliminary data analysis has shown that patient entry within 3 hours of the onset of infarction has been the exception rather than the rule. It is anticipated that this trial will be completed by mid 1983. It is hoped that the data obtained from this study will help clarify the role of thrombolysis in acute myocardial infarction.

This is a review of the important randomized trials of intracoronary and intravenous streptokinase therapy for treatment of acute myocardial infarction. Trials carried out before 1980 failed to recognize the relations between early coronary reperfusion and myocardial salvage and therefore have not been included in this review. Seven studies on intracoronary streptokinase have been reviewed. The two largest of these studies, the Western Washington trial and the Netherlands trial, show a similar reduction in early mortality. Two other small studies demonstrated a trend toward a reduction in mortality with streptokinase therapy and the other three did not. One small and two large intravenous streptokinase trials are reviewed. Of these, the large GISSI trial in Italy demonstrated a 23% reduction in mortality in patients treated within 3 hours from the onset of symptoms and the Intracoronary Streptokinase in Acute Myocardial Infarction (ISAM) trial showed a similar trend toward reduced mortality. The small Western Washington trial showed an even greater trend toward reduced mortality but this benefit was limited to patients with anterior myocardial infarction who received early therapy. It is concluded that intracoronary and intravenous streptokinase therapy, when initiated within the first 6 hours of acute myocardial infarction, reduces mortality. The therapy is most beneficial for those patients with anterior myocardial infarction and those who can receive therapy within the first 2 to 3 hours from the onset of symptoms.

To determine whether arteriographic dimensions of the acutely recanalized coronary lumen provide information about regional perfusion or clinical outcome, quantitative arteriography was used to measure minimum luminal diameter achieved with intracoronary streptokinase administration in 44 patients with acute myocardial infarction (AMI). Degree of coronary reperfusion was independently assessed visually using the criteria applied in the multicenter Thrombolysis in Myocardial Infarction study. Minimum diameter and qualitative reperfusion grade were both assessed from 172 coronary injections during thrombolysis. Partial perfusion (grade 1 or 2) was seen in 95 of 135 injections (70%) in which the minimum diameter was less than 0.6 mm and complete perfusion (grade 3) was seen in 35 of 37 injections (95%) in which it was 0.6 mm or more (p less than 0.001). Repeat cardiac catheterization was performed at 5.5 +/- 4.9 weeks after AMI (n = 20). When vessels were opened acutely to a minimum diameter of less than 0.6 mm, 5 of 12 vessels (42%) were reoccluded at the time of restudy and 8 of 29 patients (28%) died within 12 months. By contrast, 0 of 8 vessels (0%) were reoccluded when the artery was opened to a diameter of at least 0.6 mm (difference not significant), and only 1 of 15 patients (7%) died (p less than 0.05). Of the patients with grade 1 o r 2 perfusion at the end of the thrombolytic infusion, 7 of 19 (37%) died within 12 months and 2 of 4 vessels (50%) reoccluded; of the patients with grade 3 perfusion, 2 of 25 (8%) died (p less than 0.05) and 2 of 16 vessels (13%) reoccluded (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Since 1980, many data have been published concerning the pathophysiology of acute myocardial infarction and its effect on mortality. Research has been directed at developing a means of interrupting the evolution of transmural infarction and normalizing blood flow through the infarct-related vessel. Intracoronary delivery of thrombolytic agents has proved to be an effective, albeit logistically limited, means of reperfusion. The use of intravenous agents has broadened the applicability of thrombolytic therapy without severely compromising its efficacy. The recent availability of clot-selective agents has produced the potential of safely interrupting the infarction process at the earliest possible moment. This article reviews the research that has led to our use of thrombolytic agents and proposes a reasonable program of patient management in acute myocardial infarction.

Two hundred fifty patients were enrolled in a multicenter, community-based study of the efficacy of intracoronary streptokinase thrombolysis in acute myocardial infarction; 134 were randomly assigned to streptokinase therapy and 116 were controls. All patients underwent left ventricular angiography and coronary arteriography before the random assignment. The mean time from the onset of symptoms to hospitalization was 134 +/- 144 minutes (S.D), and the mean time to random assignment was 276 +/- 185 minutes. Coronary reperfusion was achieved in 68 per cent of the streptokinase-treated group. The overall 30-day mortality was 18 (7.2 per cent); there were five deaths in the streptokinase-treated group (3.7 per cent) and 13 in the control group (11.2 per cent, P less than 0.02). Fifteen of the 18 deaths occurred in patients with anterior infarction. Intracoronary streptokinase therapy resulted in a nearly threefold reduction in the 30-day mortality after hospitalization for acute myocardial infarction.

The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Trial randomized 368 patients with symptoms and signs of acute myocardial infarction of less than 6 h duration to either conventional care or 1.5 million units of intravenous streptokinase. The mean time to randomization was 209 min and 52% of patients were randomized within 3 h of symptom onset. Quantitative, tomographic thallium-201 infarct size and radionuclide ejection fraction were measured at 8.2 +/- 7.5 weeks in 207 survivors who lived within a 100 mile radius of a centralized laboratory. Overall, infarct size as a percent of the left ventricle was 19 +/- 13% for control subjects and 15 +/- 13% for treatment patients (p = 0.03). For anterior infarction in patients entered within 3 h of symptom onset, infarct size was 28 +/- 13% in the control group versus 19 +/- 15% for the treatment group (p = 0.09). Left ventricular ejection fraction was 47 +/- 15% in the control versus 51 +/- 15% in the treatment group (p = 0.08). For anterior infarction of less than 3 h duration, the ejection fraction was 38 +/- 16% in the control versus 48 +/- 20% in the treatment group (p = 0.13). By statistical analysis incorporating the nonsurvivors, p values for all of these variables were less than or equal to 0.08. There was no benefit for patients with inferior infarction or for anterior infarction of greater than 3 h duration. It is concluded that intravenous streptokinase, when given within 3 h of symptom onset to patients with anterior infarction, reduces infarct size and improves ventricular function.

Data were collected prospectively on 7553 consecutive patients undergoing coronary arteriography. The studies were performed at 13 clinics of the Collaborative Study of Coronary Artery Surgery (CASS) using brachial and femoral techniques. There were eight deaths 0--24 hours and seven deaths 24--48 hours after arteriography (2/1000). There were 15 non-fatal myocardial infarctions (MIs) 0--24 hours and four MIs 24--48 hours after arteriography (2.5/1000). Of 657 cases with left main stenosis greater than or equal to 50%, five died and three had MI. Left main disease increased risk of death by 6.8 times (p less than 0.001). Other factors increasing risk were unstable angina, congestive heart failure, multiple premature ventricular contractions, and hypertension. Of the 1187 patients studied from the brachial artery, six died (0.51%) and five had MIs (0.42%). In 6328 patients studied from the femoral artery, nine died (0.14%) and 14 had MIs (0.22%). The brachial artery technique increased the risk of death 3.6 times compared with the femoral approach (p less than 0.05). This result did not apply when analysis was restricted to laboratories with 80% or more brachial procedures. Risk was not altered by heparin. Thus, a prospective, multicenter analysis of complications reveals low risk of coronary arteriography but significant difference between two techniques.

Three hundred sixty-eight patients were randomly assigned to receive intravenous streptokinase (IVSK) (n = 191) or standard therapy (n = 177) to determine the efficacy of IVSK in the treatment of acute myocardial infarction. The mean time to treatment was 3.5 hr. At 14 days there were 12 deaths in the treatment group (6.3%) and 17 deaths in the control group (9.6%) (p = .23). Early mortality was related to infarct location. Fourteen day mortality for anterior infarctions was 10.4% for treatment with IVSK and 22.4% for control patients (p = .06) and was similar for IVSK-treated patients with inferior infarctions, 4.0% vs 1.8% (p = .32). For those randomized under 3 hr, 14 day mortality tends to be lower in treated patients, 5.2% vs 11.5% (p = .11). There was significant improvement in long-term survival for patients with anterior infarction; 2 year survival was 81% for IVSK-treated patients and 65% for control patients (p = .05). There was no improvement in survival for patients with inferior myocardial infarction (p = .27). We conclude that patients with anterior myocardial infarction have improved survival when treated within the first 6 hr of symptoms. Patients with inferior infarction do not appear to have improved survival with thrombolytic therapy. Some of this improvement in survival in patients with anterior infarction may be due to a higher frequency of revascularization procedures in the treatment group.

Thrombolytic recanalization of the obstructed coronary lumen was studied in 32 patients receiving intracoronary streptokinase for 60 to 90 min during acute myocardial infarction. The process was viewed at high arteriographic magnification and was quantified with computer-assisted measurements from repeated single-plane views. The variability of the method for this application was 0.15 to 0.18 mm on minimum diameter estimates. Structural details were seen that are not commonly appreciated at conventional magnification. The recanalized lumen appears to form along an interface between the thrombus and the vessel wall, progressively enlarging its minimum arteriographic diameter to 0.65 +/- 0.24 mm (+/- 1 SD) at the end of the short-term infusion of streptokinase reflecting a final percent stenosis of 77 +/- 10%. In nine infarct lesions found patent 5 +/- 3 weeks later, the recanalized lumen further improved an average of 0.34 mm in minimum diameter (p less than .005) and 13% stenosis (p less than .01). A thin film of contrast medium surrounding the obstructing thrombus faintly defined the boundaries of the original atherosclerotic lumen in all but two cases. The "original stenosis" measured 1.25 +/- 0.32 mm in minimum diameter and 56 +/- 14% stenosis when first visualized; it was unchanged throughout the course of infusion of streptokinase. In five patients catheterized 10 +/- 12 weeks before their infarction, the original stenosis averaged 1.15 +/- 0.22 mm in the preinfarct angiogram, as compared with 1.17 +/- 0.23 mm in its faintly defined form during thrombolytic therapy (p = NS). In 10 cases, this original lesion was less than a 50% stenosis, and in 21 cases less than 60%.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the relation between regional myocardial perfusion and regional wall motion in humans, tomographic thallium-201 imaging and two-dimensional echocardiography at rest were performed on the same day in 83 patients 4 to 12 weeks after myocardial infarction. Myocardial perfusion and wall motion were assessed independently in five left ventricular regions (total 415 regions). Regional myocardial perfusion was quantitated as a percent of the region infarcted (range 0 to 100%) using a previously validated method. Wall motion was graded on a four point scale as 1 = normal (n = 266 regions), 2 = hypokinesia (n = 64), 3 = akinesia (n = 70), 4 = dyskinesia (n = 13) or not evaluable (n = 2). Regional wall motion correlated directly with the severity of the perfusion deficit (r = 0.68, p less than 0.0001). Among normally contracting regions, the mean perfusion defect score was only 2 +/- 4. Increasingly severe wall motion abnormalities were associated with larger perfusion defect scores (hypokinesia = 6 +/- 5, akinesia = 11 +/- 7 and dyskinesia = 18 +/- 5, all p less than 0.01 versus normal. Among regions with normal wall motion, only 3% had a perfusion defect score greater than or equal to 10. Conversely, among 68 regions with a large (greater than or equal to 10) perfusion defect, only 13% had normal motion whereas 87% had abnormal wall motion. The relation between perfusion and wall motion noted for the entire cohort was also present in subgroups of patients with anterior or inferior infarction. In patients with prior myocardial infarction, the severity of the tomographic thallium perfusion defect correlates directly with echocardiographically defined wall motion abnormalities, both globally and regionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Three trials of thrombolytic therapy in myocardial infarction (MI) up to 12 hours after symptom onset were conducted to measure the mean time from onset of chest pain to hospital arrival, and mean time to therapy. The trials, using intracoronary streptokinase, intravenous streptokinase and tissue plasminogen activator (t-PA), indicated a progressive shortening of time between symptom onset and hospital arrival. The Seattle Myocardial Infarction, Triage and Intervention (MITI) trial is evaluating the safety and efficacy of thrombolytic therapy initiated by paramedics in the prehospital setting. Phase I of the trial indicates that one-half of the patients would receive prehospital therapy in the field within the first hour of symptoms, substantially sooner than what can be achieved in the hospital. Phase II of MITI, in a nonrandomized trial, will compare the use of intravenous t-PA in the field with t-PA administered in the emergency department.

Thrombolytic therapy given within the first 4 to 6 hours to patients with evolving acute MI appears to reduce in-hospital and 1-year mortality rates. In addition, patients who receive treatment in the first few hours may also benefit through improved residual left ventricular function, resulting from the preservation of ischemic myocardium. Newer agents that are more effective in lysing intracoronary thrombi are currently under development. The most promising is tissue-type plasminogen activator (t-PA), which is being evaluated in a number of large multicenter trials, including the National Heart, Lung, and Blood Institute's Thrombolysis in Myocardial Infarction (TIMI) trial. In this study researchers are also comparing the additional value of early versus delayed coronary artery angioplasty and are evaluating a subset of patients randomly assigned to early beta-blocker therapy to assess the value of adjunctive pharmacologic therapy. In the future, it is likely that studies will be carried out to determine the usefulness of thrombolytic therapy given to patients by paramedics before hospitalization. Such a study is being planned in several communities. It is hoped that by means of prehospital therapy, it may be possible to treat a substantial group of patients with symptoms and electrocardiographic findings of acute MI before extensive left ventricular myocardial necrosis has occurred. If this goal can be realized, it may be possible to achieve a very substantial reduction in mortality resulting from acute MI. Initial experience with prehospital intravenous streptokinase therapy has already been reported from Jerusalem, Israel.(ABSTRACT TRUNCATED AT 250 WORDS)

The Western Washington Intravenous Streptokinase Trial randomized 368 patients with acute myocardial infarction to receive either intravenous streptokinase or standard therapy. The ventriculograms and coronary angiograms obtained in 170 patients 10.4 +/- 7.4 days after infarction were analyzed to evaluate the effects of thrombolytic therapy on global and regional systolic function. Streptokinase treatment resulted in a higher patency rate of the infarct-related artery (68.5%) than did standard therapy (44.8%) (p = 0.003). Ejection fraction was higher in streptokinase-treated patients (54% vs. 51%, p = 0.056), and the difference was most marked in patients with anterior myocardial infarction (53% vs. 44%, p = 0.03). Regional wall motion was measured by the centerline method and expressed in mean +/- SD motion in 52 normal subjects. There was a trend toward better function of the infarct zone in streptokinase-treated patients (SD, -2.48 vs. -2.70, p = 0.24). Additionally, streptokinase-treated patients had significantly better wall motion of noninfarct areas (SD, 0.36 vs. -0.08, p = 0.02). Treatment effects on function of noninfarct regions were most apparent in the subset of patients with multivessel disease. Thus, intravenous streptokinase preserves left ventricular function in patients with acute myocardial infarction. This benefit includes favorable effects on the function of regions remote from the site of infarction.