Emergency coronary artery bypass surgery preserves global and regional left ventricular function after intravenous tissue plasminogen activator therapy for acute myocardial infarction

Emergency coronary bypass surgery was performed in 24 (6.2%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Multicenter Trial. Intravenous tissue plasminogen activator was administered 2.6 +/- 0.7 h and bypass surgery was performed 7.3 +/- 1.9 h after the onset of infarction. Infarct artery patency was achieved in 21 (88%) of the 24 patients (pharmacologically in 18 or mechanically with coronary angioplasty in 3) in the catheterization laboratory before bypass surgery. The indication for surgery was left main or equivalent coronary artery disease in 7 patients, coronary anatomy unsuitable for angioplasty in 4 patients and unsuccessful coronary angioplasty in 13 patients. A coronary perfusion catheter was inserted before surgery in 11 of 13 patients with unsuccessful angioplasty. All three deaths occurred postoperatively in patients with preoperative cardiogenic shock. Three patients required surgical reexploration for postoperative hemorrhage. Comparison of preoperative and predischarge contrast left ventriculograms demonstrated significant preservation of global (left ventricular ejection fraction 49 +/- 6 to 56 +/- 6%; p = 0.008) and regional (standard deviation/chord -2.6 +/- 0.5 to -1.5 +/- 1.1; p = 0.001) left ventricular function. Emergency coronary bypass surgery can be performed with a low morbidity and mortality in patients treated with intravenous tissue plasminogen activator therapy for acute myocardial infarction. Such therapy is associated with significant preservation of global and regional (infarct zone) left ventricular function.     

Value of percutaneous transluminal coronary angioplasty after unsuccessful intravenous streptokinase therapy in acute myocardial infarction

The effect of sequential high-dose intravenous streptokinase (SK) (1.5 million units) followed by emergency percutaneous transluminal coronary angioplasty (PTCA) on preserving left ventricular function was assessed prospectively in 34 patients with acute myocardial infarction (AMI). Intravenous SK therapy was initiated 2.6 +/- 1.3 hours (mean +/- standard deviation) after the onset of chest pain. Urgent coronary angiography showed persistent total occlusion in 13 patients, significant diameter stenosis (70 to 99%) in 18 patients and a widely patent artery (less than 50% stenosis) in 3 patients. Emergency PTCA was performed in 29 patients 5.0 +/- 2.1 hours after symptom onset. Successful recanalization was achieved in 33 of the 34 patients (97%) treated with sequential therapy. Repeat contrast ventriculograms recorded 7 to 10 days after intervention in 23 patients showed that the left ventricular ejection fraction increased from 53 +/- 12% to 59 +/- 13% (area-length method, p less than 0.002). Regional wall motion of the infarcted segments improved from -2.7 +/- 1.1 to -1.5 +/- 1.7 SD/chord (centerline method, p less than 0.003). In the subgroup of patients with an occluded artery on initial angiography (group A, n = 10), both global left ventricular ejection fraction (49 +/- 12% vs 59 +/- 12%, p less than 0.002) and regional wall motion (-3.2 +/- 1.0 vs -1.9 +/- 1.7 SD/chord, p less than 0.002) improved significantly. In contrast, no significant improvement was seen in patients with a patent artery on initial angiography (n = 13). Thus, sequential intravenous SK and emergency PTCA is efficacious in achieving coronary reperfusion and in improving both global and regional left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial infarction with minimal coronary atherosclerosis in the era of thrombolytic reperfusion. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group

The incidence of minimal residual atherosclerotic coronary obstruction after successful intravenous thrombolytic therapy was evaluated in 799 patients with acute myocardial infarction. Minimal residual coronary obstruction (less than or equal to 50%) was observed on selective coronary angiography performed 90 min after initiation of thrombolytic therapy in 43 patients (5.5%). In 42 other patients (5.4%), a greater than 50% but less than 100% residual stenosis noted at 90 min demonstrated further resolution of obstruction to less than 50% at an angiographic follow-up study 7 to 10 days later. Patients with minimal residual coronary obstruction were significantly younger (52 +/- 10.7 versus 56.7 +/- 10 years; p = 0.002) and had less multivessel coronary disease (p less than 0.001), better initial left ventricular ejection fraction (54 +/- 12% versus 50.2 +/- 11.4%; p = 0.006) and a lower in-hospital mortality rate (1% versus 7%; p = 0.04) than did patients who had a significant (greater than 50%) residual coronary obstruction after intravenous thrombolysis. Long-term follow-up study of patients with a minimal coronary lesion (average 1.5 +/- 0.6 years) and those with significant residual stenosis (average 1.6 +/- 0.7 years) demonstrated that the incidence of death (2.4% in patients with minimal stenosis versus 3.5% in those with significant stenosis) and recurrent myocardial infarction (5% each) were similar in both groups. New strategies are needed to prevent coronary rethrombosis in patients with minimal atherosclerosis after thrombolytic therapy for acute myocardial infarction.     

A prospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Kentucky Acute Myocardial Infarction Trial (KAMIT) Group

BACKGROUND. The potential benefits of combination thrombolytic agents in the treatment of myocardial infarction remain uncertain. In a small pilot study, we demonstrated that combining half-dose tissue-type plasminogen activator (t-PA) with streptokinase (SK) achieved a high rate of infarct vessel patency and a low rate of reocclusion at half the cost of full-dose t-PA. METHODS AND RESULTS. We designed a prospective trial in which 216 patients were randomized within 6 hours of myocardial infarction to receive either the combination of half-dose (50 mg) t-PA with streptokinase (1.5 MU) during 1 hour or to the conventional dose of t-PA (100 mg) during 3 hours. Acute patency was determined by angiography at 90 minutes, and angioplasty was reserved for failed thrombolysis. Heparin and aspirin regimens were maintained until follow-up catheterization at day 7. Acute patency was significantly greater after t-PA/SK (79%) than with t-PA alone (64%, p less than 0.05). After angioplasty for failed thrombolysis, acute patency increased to 96% in both groups. Marked depletion of serum fibrinogen levels occurred after t-PA/SK compared with t-PA alone at 4 hours (37 +/- 36 versus 199 +/- 66 mg/dl, p less than 0.0001) and persisted 24 hours after therapy (153 +/- 66 versus 252 +/- 75 mg/dl, p less than 0.0001). Reocclusion (3% versus 10%, p = 0.06), reinfarction (0% versus 4%, p less than 0.05), and need for emergency bypass surgery (1% versus 6%, p = 0.05) tended to be less in the t-PA/SK group. Greater myocardial salvage was apparent in the t-PA/SK group as assessed by infarct zone function at day 7 (-1.9 SD/chord versus -2.3 SD/chord after t-PA alone, p less than 0.05). In-hospital mortality (6% versus 4%) and serious bleeding (12% versus 11%) were similar between the two groups. CONCLUSIONS. These results suggest that a less expensive regimen of half-dose t-PA with SK yields superior 90-minute patency and left ventricular function and a trend toward reduced reocclusion compared with the conventional dose of t-PA.     

Factors that determine recovery of left ventricular function after thrombolysis in patients with acute myocardial infarction

The coronary and ventricular angiograms of 47 patients with acute myocardial infarction in whom reperfusion was achieved by intracoronary streptokinase were quantitatively analyzed to determine the factors that affect recovery of regional left ventricular function after reperfusion. Hypokinesis in the infarct region was measured by the centerline method and expressed in terms of standard deviations (SDs) from normal. Severity of coronary artery stenosis was measured quantitatively. Hypokinesis showed more significant improvement after thrombolysis in patients with minimum stenosis diameter of greater than 0.4 mm than in those with severe residual stenosis, i.e., stenosis producing a minimum diameter of 0.4 mm or less (1.0 +/- 1.3 SD/chord, n = 31, vs 0.0 +/- 0.9 SD/chord, n = 7; p less than .05). Improvement in hypokinesis was greater in patients who received thrombolytic therapy within 2 hr than in those treated later (2.1 +/- 1.1, n = 8, vs 0.7 +/- 1.0 SD/chord, n = 28; p less than .001). These results indicate that angiographic reperfusion alone may not be sufficient: reperfusion must provide adequate flow and be achieved early to salvage myocardial function.     

Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. TAMI-5 Study Group

This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 +/- 11% (vs. 54.3 +/- 10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 +/- 1.07 SD/chord (vs. -2.46 +/- 1.19 SD/chord; p = 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)     

Implications for patient triage from survival and left ventricular functional recovery analyses in 500 patients treated with coronary angioplasty for acute myocardial infarction

The in-hospital course of 500 consecutive patients treated with coronary angioplasty for acute myocardial infarction was reviewed in relation to their clinical and angiographic presentation and angioplasty outcome to determine which patients benefit most from successful angioplasty in this setting. Patient age was 56 +/- 11 years (mean +/- SD) and 78% were men; 46% had anterior myocardial infarction, 49% received concomitant intravenous thrombolytic therapy, left ventricular ejection fraction was 47 +/- 11% and median time to angioplasty was 4.7 h (range 1 to 24). Angioplasty was successful in 78% of patients and partially successful in 7% of patients; the overall in-hospital mortality rate was 10.2%. Multivariate analysis found six independent correlates (p less than 0.05) of in-hospital mortality: left ventricular ejection fraction less than or equal to 30%, lack of postangioplasty infarct artery patency, age greater than 65 years, recurrent ischemia after successful angioplasty, emergency bypass surgery and arterial pressure on admission to the catheterization laboratory less than 100 mm Hg. After consideration of these predictors of survival in multivariate analyses, angioplasty success still was independently correlated with improved in-hospital survival for patients with cardiogenic shock (p = 0.002) and anterior myocardial infarction (p = 0.007). A trend toward an independent beneficial effect of successful angioplasty on survival was also noted in patients with inferior wall infarction and precordial ST segment depression (p = 0.063) and for all patients who were hypotensive on admission to the catheterization laboratory, regardless of the infarct site (p = 0.057).(ABSTRACT TRUNCATED AT 250 WORDS)     

Two-year outcome after angiographically documented myocardial reperfusion for acute coronary occlusion. Thrombolysis and Angioplasty Study Group

Reperfusion therapy has been clearly shown to decrease the early mortality after acute myocardial infarction, but the impact of this therapy on long-term survival has been less extensively evaluated. This study reports the extended follow-up of a large cohort of 810 patients treated with intravenous thrombolytic therapy combined, when considered necessary to maintain or augment infarct vessel patency, with mechanical reperfusion therapies. Each patient underwent coronary angiography within 2 hours of the initiation of the thrombolytic infusion. Coronary angioplasty was performed in 62% of the patients before hospital discharge and 21% underwent coronary artery bypass graft surgery. Follow-up was obtained in 96% to a mean of 18.8 months (range, 1.5 to 48 months). All-cause mortality over this period was 3.3%; 2.1% died from cardiac causes. Nonfatal reinfarction occurred in 5.1%. Although the low event rate limits the validity of statistical comparisons, the patients who survived the follow-up period tended to be younger (56 +/- 10 vs 65 +/- 7 years), to have better predischarge left ventricular function (left ventricular ejection fraction, 52 +/- 11 vs 46 +/- 13%) and to have a lower prevalence of multivessel coronary artery disease (45 vs 67%). This excellent long-term survival may, in part, reflect the exclusion of high-risk patients from enrollment in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) studies. It may also be attributable, however, to the frequent use of combined thrombolysis and mechanical revascularization in this population.     

Early reperfusion therapy improves left ventricular function after acute inferior myocardial infarction associated with right coronary artery disease

Quantitative global and regional ventriculographic analysis was performed acutely and 1 week later in 46 patients undergoing reperfusion procedures within 6 hours of acute inferior myocardial infarction due to right coronary artery disease. While serial improvement in global left ventricular ejection fraction was not demonstrated for the group, infarct zone regional wall motion did improve (-2.7 +/- 0.9 vs -2.3 +/- 1.4 SD/chord, p less than 0.007). Serial improvement in global ejection fraction was demonstrated in the subgroup of patients treated within 2 hours of symptom onset (55 +/- 10 vs 62 +/- 10%; n = 5; p less than 0.03). Infarct zone regional wall motion improved serially only in the subgroup of patients treated within 3 hours of symptom onset (-2.4 +/- 1.1 vs -1.3 +/- 1.7 SD/chord; n = 11; p less than 0.007). Patients with initially patent arteries had a higher ejection fraction on follow-up catheterization than did those with initially occluded vessels (61 +/- 11 vs 55 +/- 7%; p less than 0.02), and patients with patent arteries at follow-up had a higher ejection fraction than did those whose arteries were occluded (60 +/- 9 vs 48 +/- 4%; p less than 0.0001). We conclude that significant improvement in global and regional left ventricular function in patients with inferior myocardial infarction is possible when reperfusion therapy is begun early or when arterial patency is achieved.     

Acute effects of parenteral beta-blockade on regional ventricular function of infarct and noninfarct zones after reperfusion therapy in humans.

Although the mechanism is unknown, clinical trials have suggested that intravenous beta-adrenergic blockade may prevent early cardiac rupture after myocardial infarction. Previous studies have examined effects of beta-blockers on global left ventricular function after myocardial infarction; however, few data exist regarding their immediate effects on regional function or in patients after successful reperfusion. Therefore, 65 patients in whom thrombolysis with or without coronary angioplasty achieved reperfusion at 4.6 +/- 1.7 h from symptom onset were studied. Low osmolarity contrast ventriculograms were obtained immediately before and after administration of 15 mg of intravenous metoprolol (n = 54) or placebo (n = 11). Intravenous metoprolol immediately decreased heart rate (from 92 to 76 beats/min, p less than 0.0001), increased left ventricular diastolic volume (from 150 to 163 ml, p less than 0.001) and systolic volume (from 72 to 77 ml, p less than 0.0005) but did not change systolic and diastolic pressures. Although there was no difference in ejection fraction after metoprolol, centerline chord analysis revealed reduced noninfarct zone motion (from 0.41 to 0.12 SD/chord, p less than 0.05), improved infarct zone motion (from -3.1 to -2.9 SD/chord, p less than 0.01) and smaller circumferential extent of hypokinesia (from 30 to 27 chords, p less than 0.05). Patients with dyskinesia of the infarct zone had the most striking improvement in infarct zone wall motion. Because these changes occurred immediately after beta-blockade, they could not be attributed to myocardial salvage. No significant changes in heart rate, left ventricular volumes or regional wall motion were apparent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of thrombolysis and angioplasty in myocardial infarction--phase 5 randomized trial. TAMI Study Group

Recent trials of myocardial reperfusion using single-agent thrombolytic therapy and sequential cardiac catheterization have supported a conservative approach to the patient with acute myocardial infarction. To evaluate combination thrombolytic therapy and the role of a previously untested strategy for the aggressive use of cardiac catheterization, we performed a multicenter clinical trial with a 3 x 2 factorial design in which 575 patients were randomly allocated to one of three drug regimens--tissue-type plasminogen activator (t-PA) (n = 191), urokinase (n = 190), or both (n = 194) - and one of two catheterization strategies--immediate catheterization with angioplasty for failed thrombolysis (n = 287) or deferred predischarge catheterization on days 5-10 (n = 288). Patients with contraindications to thrombolytic therapy, cardiogenic shock, or age of more than 75 years were excluded. Global left ventricular ejection fraction was well preserved and almost identical at predischarge catheterization (54%), regardless of the catheterization or thrombolytic strategy used (p = 0.98). Combination thrombolytic therapy was associated with a less complicated clinical course, most clearly documented by a lower rate of reocclusion (2%) compared with urokinase (7%) and t-PA (12%) (p = 0.04) and a lower rate of recurrent ischemia (25%) compared with urokinase (35%) and t-PA (31%). When a composite clinical end point (e.g., death, stroke, reinfarction, reocclusion, heart failure, or recurrent ischemia) was examined, combination thrombolytic therapy was associated with greater freedom from any adverse event (68%) compared with either single agent (urokinase, 55%; t-PA, 60%) (p = 0.04) and with a less complicated clinical course when the composite clinical end points were ranked according to clinical severity (p = 0.024). Early patency rates were greater with combination therapy, although predischarge patency rates after considering interventions to maintain patency were similar among drug regimens. No difference in bleeding complication rates was observed with any thrombolytic regimen. The aggressive catheterization strategy led to an overall early patency rate of 96% and a predischarge patency rate of 94% compared with a 90% predischarge patency in the conservative strategy (p = 0.065). The aggressive strategy improved regional wall motion in the infarct region (-2.16 SDs/chord) compared with deferred catheterization (-2.49 SDs/chord) (p = 0.004). More patients treated with the aggressive strategy were free from adverse outcomes (67% versus 55% in the conservative strategy, p = 0.004), and the clinical course was less complicated when the adverse outcomes were ranked according to severity (p = 0.016). No significant increase in use of blood products resulted from the aggressive strategy.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI Phase I) trial

In Phase I of the NHLBI trial of Thrombolysis in Myocardial Infarction (TIMI), 290 patients admitted within 7 hr after onset of acute infarction were randomly assigned to intravenous treatment with either streptokinase (SK) or recombinant tissue-type plasminogen activator (rt-PA). Left ventricular function was measured from contrast ventriculograms in 145 patients with both pretreatment and predischarge studies analyzable. Regional wall motion in the infarct site was measured by the centerline method and expressed in units of standard deviations (SDs) from the mean motion in 52 normal subjects. Patients treated with rt-PA (n = 77) achieved a significantly higher reperfusion rate after 90 min of treatment. Perfusion of the infarct-related artery improved from visual grade 0 or 1 (total occlusion or penetration without perfusion) to grade 2 or 3 (partial or full reperfusion) in 62% receiving rt-PA vs 31% receiving SK (n = 68) (p less than .001). However, the ejection fraction did not change significantly from before treatment to before discharge in either treatment group (+0.7 +/- 6.7% vs +1.0 +/- 8.3%, respectively). A small but significant increase in regional wall motion was observed in each of the two groups (+0.4 +/- 0.8 vs +0.3 +/- 0.8 SD/chord, respectively; each p less than .001 compared with baseline). This was countered by declines in the hyperkinesis of the noninfarct region (-0.3 +/- 1.0 SD/chord [p = .01] compared with baseline and -0.2 +/- 1.0 SD/chord [p = .23], respectively). Analysis of the combined groups revealed that the ejection fraction increased only in patients who achieved reperfusion by 90 min after onset of therapy or who had subtotal occlusions initially. There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery.     

Plasminogen Activator Italian Multicenter Study (PAIMS): comparison of intravenous recombinant single-chain human tissue-type plasminogen activator (rt-PA) with intravenous streptokinase in acute myocardial infarction

A single chain preparation of recombinant tissue-type plasminogen activator (rt-PA) was compared with intravenous streptokinase to determine coronary thrombolytic efficacy in patients with acute myocardial infarction less than 3 h old. Eighty-six patients were randomly selected to receive the intravenous cumulative dose of 100 mg rt-PA and 85 patients to receive 1.5 million units streptokinase. At 240 min after initiation of the thrombolytic therapy noninvasive signs of sustained reperfusion occurred in 79% of patients in both groups (p = NS). Patency of the infarct-related vessel at follow-up angiography was observed in 81% of patients in the rt-PA group and 74% of patients in the streptokinase group (p = NS). At hospital discharge, compared with admission, echocardiographically determined left ventricular ejection fraction increased from 52 +/- 11% to 56 +/- 10% (p less than 0.01) in the rt-PA group; changes in the streptokinase group (50 +/- 9% to 51 +/- 11%) were not significant. A nadir value of less than 1 g/liter fibrinogen plasma level occurred in 6 patients (7%) receiving rt-PA versus 74 patients (87%) receiving streptokinase (p less than 0.0001). Plasma levels of fibrin(ogen) degradation products were more than doubled in the streptokinase group (p less than 0.01). One patient in the streptokinase group developed a fatal intracranial hemorrhage; five others showed a decline in hemoglobin greater than or equal to 5 g/dl. Other clinical events in the streptokinase-treated group included allergic reactions (four patients) and intrahospital reinfarction (two patients). None of these events occurred in the rt-PA group.(ABSTRACT TRUNCATED AT 250 WORDS)     

A prospective, placebo-controlled, randomized trial of intravenous streptokinase and angioplasty versus lone angioplasty therapy of acute myocardial infarction.

BACKGROUND. The value of routine administration of intravenous thrombolytic agents during percutaneous transluminal coronary angioplasty (PTCA) therapy of acute myocardial infarction (MI) has not been determined. Therefore, we prospectively randomized 122 patients with evolving MI to PTCA therapy with or without adjunctive intravenous streptokinase therapy. METHODS AND RESULTS. Patients with ECG ST segment elevation who presented within 4 hours of symptom onset, had no contraindication to thrombolytic therapy, and were not in cardiogenic shock were enrolled. They were treated immediately with intravenous heparin (10,000 units) and oral aspirin (325 mg) and randomized to treatment with placebo or streptokinase (1.5 M units) administered intravenously over 30 minutes. Patients then were taken immediately to the catheterization laboratory, and those with suitable coronary anatomy underwent immediate PTCA. Subsequent clinical course, serial radionuclide ventriculography, and 6-month repeat angiography were analyzed. A total of 106 patients were treated with PTCA. Use of PTCA was similar for placebo (92%) and streptokinase (83%) groups. Angioplasty was successful in 95% of patients, with no difference in placebo (93%) and streptokinase (98%) groups. Serial radionuclide ventriculography demonstrated no difference in 24-hour (52 +/- 12% versus 50 +/- 12%) or 6-week (51 +/- 12% versus 51 +/- 13%) ejection fraction values for placebo and streptokinase groups, respectively. Contrast ventriculography demonstrated improvement in immediate (54 +/- 12%) versus 6-month (60 +/- 15%, p < 0.05) values for the overall group. No differences in 6-month values were present (58 +/- 15% versus 62 +/- 15%, p = NS) for placebo and streptokinase groups, respectively. Coronary angiography was performed in 75% of the 90 patients eligible for restudy. Arterial patency was 87% at 6 months, and coronary restenosis was present in 38% of patients. No differences in chronic patency or restenosis were detected for the two treatment groups. Although adjunctive intravenous streptokinase therapy did not improve outcome, it did complicate the hospital course. Hospitalization was longer (9.3 +/- 5.0 versus 7.7 +/- 4.4 days, p = 0.046) and more costly ($25,191 +/- 15,368 versus $19,643 +/- 7,250, p < 0.02). Transfusion rate was higher (39% versus 8%, p = 0.0001) and need for emergency coronary bypass surgery was greater (10.3% versus 1.6%, p = 0.03) for the streptokinase-treated patients. CONCLUSIONS. Adjunctive intravenous streptokinase therapy does not enhance early preservation of ventricular function, improve arterial patency rates, or lower restenosis rates after PTCA therapy of acute MI. Hospital course is longer, more expensive, and more complicated. For these reasons, PTCA therapy of acute MI should not be routinely performed with adjunctive intravenous streptokinase therapy.     

Effect of streptokinase on left ventricular modeling and function after myocardial infarction: the GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) Trial

It has been shown that streptokinase administration at the time of acute myocardial infarction reduces mortality significantly, and that this reduction in mortality should be related to salvage of jeopardized myocardium and preservation of left ventricular function. To better define the relation between thrombolytic therapy and left ventricular modeling and function after acute myocardial infarction, 331 consecutive patients enrolled in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial were studied by two-dimensional echocardiography just before discharge from the hospital. A 6 month follow-up examination was also available in 232 of these patients. Ventricular volumes were computed from an apical four chamber view, according to a previously published algorithm. An infarct size index was also semiquantitatively assessed, according to the number of akinetic and dyskinetic segments in an 11 segment left ventricular model. At predischarge examination, the 161 patients assigned to streptokinase treatment showed smaller ventricular volumes (end-diastolic volume 119.3 +/- 49.7 versus 134.5 +/- 57.8 ml [p = 0.011]; end-systolic volume 65.4 +/- 36.4 versus 74.9 +/- 45.7 ml [p = 0.036]) and smaller regional wall motion index (2.2 +/- 1.9 versus 2.7 +/- 1.9 segments; p = 0.019) compared with values in the 170 patients assigned to standard care; there was no difference in ejection fraction (46.6 +/- 14.1 versus 45.9 +/- 14.9%; p = 0.64). For both groups of patients, there was a significant relation between end-systolic volume and regional wall motion index (p less than 0.001); for large and similar extents of infarct size, ventricular volume was smaller in patients assigned to thrombolytic treatment than in patients assigned to standard care. At 6 months' follow-up, the differences in volume and regional dysfunction detected at the early examination persisted: 110.8 +/- 47.6 versus 127.9 +/- 53.8 ml for end-diastolic volume (p = 0.001), 56.3 +/- 33.6 versus 69.4 +/- 42.1 ml for end-systolic volume (p = 0.001) and 1.8 +/- 1.8 versus 2.3 +/- 1.8 segments for regional wall motion index (p = 0.001). Again, for comparable extents of infarct size, end-systolic volume was smaller in patients who received streptokinase (n = 110) than in those assigned to conventional treatment (n = 122). It is concluded that streptokinase improves left ventricular modeling and function in patients with myocardial infarction, reducing the extent of regional wall motion abnormalities and lessening postinfarction ventricular dilation. The beneficial effects persist up to 6 months.     

Direct coronary angioplasty in acute myocardial infarction: outcome in patients with single vessel disease

Percutaneous transluminal coronary angioplasty was performed as primary therapy in 215 consecutive patients (aged 56 +/- 11 years, 75% male) with acute myocardial infarction and single vessel coronary artery disease. Wide patency of the infarct-related artery was restored in 212 patients (99%). Complications consisted of one urgent coronary bypass operation (0.5%); there were no procedural deaths. A recurrent ischemic event before discharge occurred in eight patients (4%). The in-hospital mortality rate was 1%; five of six patients presenting with cardiogenic shock were alive at discharge. In 126 patients in whom predischarge angiography was performed, the ejection fraction improved from 55 +/- 12% to 61 +/- 12% (p less than 0.005) and increased by greater than or equal to 5% units in 66 patients (52%). Regional wall motion improved in 60 patients (48%). By multivariate analysis, a depressed initial ejection fraction, a limited increase in serum creatine kinase, young age and sustained patency of the infarct-related artery were found to be independent predictors of improvement in left ventricular function. Follow-up data were available in 214 patients (99.5%) at a mean interval of 35 months. The actuarial 3 year cardiac survival rate was 92%. By multivariate analysis, only the baseline ejection fraction correlated with long-term cardiac survival. Nine patients (4%) sustained a late nonfatal myocardial infarction, and 11 patients (5%) underwent subsequent coronary bypass surgery. At late follow-up study, 149 (77%) of 194 patients alive were free of angina. In summary, in patients with acute myocardial infarction and single vessel disease, coronary angioplasty without prior thrombolytic therapy can be performed with a high success rate and few procedural complications. After direct angioplasty, regional wall motion and global ejection fraction improve in 50% of patients, especially in those with depressed initial left ventricular function. This approach results in an excellent early and late event-free survival.     

Immediate coronary angioplasty versus intravenous streptokinase in acute myocardial infarction: Left ventricular ejection fraction,hospital mortality and reinfarction

Objectives. The purpose of the present study was to compare intravenous Streptokinase therapy with immediate coronary angioplasty without antecedent thrombolytic therapy with regard to left ventricular function and hospital mortality and reinfarction.Background. Despite the widespread use of intravenous thrombolytic therapy and immediate percutaneous transluminal coronary angioplasty, these two strategies to treat patients with an acute myocardial infarction have only recently been compared in randomized trials. Coronary angioplasty has been shown to result In a higher patency rate of the Infant-related coronary artery, with a less severe residual stenotic lesion, compared with streptokinase therapy, but whether this more favorable coronary anatomy results in clinical benefit remair to be established.Methods. We studied 301 patients with acute myocardial infarction randomly assigned to undergo immediate coronary angioplasty without antecedent thrombolytic therapy or to receive intravenous streptokinase therapy. Before discharge left ventricular ejection fraction was measured by radionuclide scanning.Results. The in-hospital mortality rate in the streptokinase group was 7% (11 of 149 patients) compared with 2% (3 of 152 patients) in the angioplasty group (p = 0.024). In the streptokinase group recurrent myocardial infarction occurred in 15 patients (10%) versus in 2 (1%) in the angioplasty group (p < 0.001). Either death or nonfatal reinfarction occurred in 23 patients (15%) in the streptokinase group and in 5 patients (3%) in the angioplasty group (p = 0.001). Left ventricular ejection fraction was 44 ± 11% (mean ± SD) in the streptokinase group versus 50 ± 11% in the angioplasty group (p < 0.001).Conclusions. These findings indicate that immediate coronary angioplasty without antecedent thrombolytic therapy results in better left ventricular function and lower risk of death and recurrent myocardial infarction than treatment with intravenous streptokinase.     

Increased exercise thallium-201 lung uptake: a noninvasive prognostic index in two-vessel coronary artery disease

To determine the physiologic impact of two-vessel coronary artery disease and its effect on prognosis, a series of clinical, angiographic, exercise and quantitative thallium-201 (Tl-201) imaging parameters were analyzed in 85 consecutive two-vessel coronary artery disease patients followed for 52 +/- 27 months after coronary angiography and Tl-201 scintigraphy. End points were cardiac death (n = 3), myocardial infarction (n = 6) and coronary bypass graft surgery more than three months after testing (n = 16). Using Cox Hazards survival analysis, early cardiac events were not predicted by: myocardial infarction or anginal history; resting left ventricular function; exercise blood pressure response; angina or severity of ECG ST segment depression (mm); Tl-201 defect size; redistribution or clearance; angiographic patterns; or the presence of proximal left anterior descending disease. Significant predictors of adverse cardiac events were: increased exercise lung to heart Tl-201 ratio (0.59 +/- 0.12 versus 0.46 +/- 0.1; P less than 0.0001); ECG lead extent of ST segment depression (P less than 0.03); and exercise heart rate response (P less than 0.047). Event-free survival for patients with normal and abnormally increased lung to heart Tl-201 ratios at 48 months was 76% versus 63% (P less than 0.003). It was concluded that two-vessel coronary artery disease survival correlates with exercise Tl-201 uptake which reflects exercise induced left ventricular dysfunction.     

Exercise-induced ST segment elevation 2 weeks after uncomplicated myocardial infarction: contributing factors and prognostic significance

To define the prevalence and clinical significance of exercise-induced ST segment elevation during predischarge treadmill testing after uncomplicated acute myocardial infarction confirmed by serum MB creatine kinase (CK) activity, 241 consecutive patients were prospectively investigated with quantitative exercise thallium-201 scintigraphy, rest radionuclide ventriculography and coronary angiography at 10 +/- 3 days. All patients received customary care, and in none was thrombolytic therapy or emergency coronary angioplasty employed. Eighty-two patients (34%) had exercise-induced ST segment elevation of greater than or equal to 1 mm above rest baseline. These patients were similar to the 159 patients without this finding with respect to history of prior infarction, the Norris coronary prognostic index, exercise duration, metabolic equivalents (METs) achieved and peak heart rate-blood pressure product. The frequency of inducible myocardial ischemia and extent of angiographic coronary disease was also comparable in the two groups. Findings associated with larger infarct size and transmural extent of infarction were more common in patients with exercise-induced ST segment elevation than in those without, including higher peak CK values (1,235 +/- 1,037 versus 942 +/- 915 mumol/min per liter, p less than 0.026), lower left ventricular ejection fraction (43 +/- 12 versus 51 +/- 10%, p less than 0.001), a higher prevalence of pathologic Q waves in greater than or equal to 2 contiguous infarct-related leads (80 versus 55%, p less than 0.001), more persistent thallium-201 defects (2.2 +/- 1.1 versus 1.4 +/- 1.1, p less than 0.001), abnormally increased lung uptake of thallium (33 versus 18%, p less than 0.01) and a greater number of akinetic or dyskinetic segments (3.2 +/- 2.5 versus 1.4 +/- 1.9, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of Left Ventricular Functional Recovery After Thrombolytic Therapy and/or Immediate Coronary Angioplasty in Acute Myocardial Infarction

To determine the effect of thrombolytic therapy and/or immediate coronary angioplasty (PTCA) on left ventricular function, 129 patients with acute transmural myocardial infarction were retrospectively studied. Treatment strategies included thrombolytic therapy alone (n = 29), PTCA alone (n = 41), and combined thrombolytic therapy and PTCA (n = 59). Left ventricular ejection fraction (LVEF) and infarct zone regional wall motion (RWM) were determined from contrast ventriculography obtained acutely and at day 7–10. In the overall group, there was a 2 ± 9% increase in LVEF (p < 0.02) and a 0.7 ± 1.2 SD/chord increase in RWM (p < 0.0001) between day 1 and day J-10. Patients with a patent infarct vessel at day 7–10 had a more significant change (Δ) in LVEF (3 ± 8 vs ?5 ± 9%, p = 0.0002) and RWM (0.8 ± 1.2 vs 0.1 ± 1.0 SD/chord, p < 0.02) than patients with an occluded vessel. Patients with a residual stenosis < 70% at day 7–10 manifested a greater ΔLVEF (3 ± 8vs-5 ± 9%, p < 0.01) and ΔRWN (0.9 ± 1.2 vs 0.1 ± 1.0 SD/ chord, p < 0.05) than patients who were occluded. There was a negative correlation between residual stenosis and ΔRWM (p < 0.04). Patients treated < 3 hours after symptom onset demonstrated a more significant ΔRWM when compared to patients treated ≥ 3 hours (1.0 ± 1.3 vs 0.5 ± 1.1 SD/chord, p < 0.04). Patients treated with combined thrombolytic therapy and PTCA were observed to have a greater ARWM than patients treated with thrombolytic therapy alone (0.8 ± 1.2 vs 0.2 ±0.9 SD/chord, p < 0.05). Patients with an LVEF > 40% demonstrated a more significant ΔLVEF than patients; ± 40% (7 ± 8vs 1 ± 8%, p < 0.007). A significant improvement in ΔLVEF was noted only in patients with an anterior infarction when compared to patients with an inferior infarction. Age, sex, presence of multivessel disease, history of prior myocardial infarction, initial patency of the infarct vessel, and presence of collaterals had no effect on left ventricular function. Stepwise multiple regression identified residual stenosis, time to treatment, and the degree of initial global impairment as the major joint predictors of ventricular functional recovery. (J Interven Cardiol 1988:1:3)