Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study

BACKGROUND. Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study. METHODS AND RESULTS. One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died. CONCLUSIONS. The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications.     

Rescue thrombolysis: alteplase as adjuvant treatment after streptokinase in acute myocardial infarction.

BACKGROUND--In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS--Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS--Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION--Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.     

Preservation of global and regional left ventricular function after early thrombolysis in acute myocardial infarction

The effect of early myocardial reperfusion (within 4 hours after onset of symptoms) on regional left ventricular function in patients with acute myocardial infarction has been quantitated by analysis of segmental wall motion. Of 533 patients randomized either to conventional coronary care unit therapy or to a reperfusion strategy, in 332 high quality angiograms were obtained 2 to 8 weeks after the onset of myocardial infarction. In those assigned to thrombolytic therapy, angiographic data were also available after acute reperfusion. Analysis on an "intention to treat" basis revealed significant preservation of left ventricular function after thrombolytic therapy (ejection fraction 53%) compared with conventional treatment (ejection fraction 47%). In addition, wall motion analysis showed significant improvement of regional function in the infarct zone in both inferior and anterior infarction. In addition, significant changes occurred in regional function of the remote "noninfarct zone" in the acute as well as the chronic stage. It is concluded that improved regional and global left ventricular function can be achieved with early reperfusion and that this is the likely explanation for the reduction of early and late mortality after thrombolysis observed in this study.     

Comparative safety of thrombolytic agents.

Three available thrombolytic agents, streptokinase, alteplase, and anistreplase, have been shown to have similar effects on preservation of left ventricular function and mortality reduction after acute myocardial infarction (AMI). The agents are, however, quite different with respect to their safety profiles. Clinical trials to date suggest that alteplase (tissue plasminogen activator) or anistreplase administration is associated with a high incidence of cerebral hemorrhage. In contrast, streptokinase is associated with a low rate of cerebral hemorrhage. Streptokinase and anistreplase are associated with a higher risk of allergic reaction when compared with alteplase. Hypotension is also more common with streptokinase and anistreplase, but occurs significantly with alteplase as well. Alteplase is associated with a lower reinfarction rate when compared with streptokinase and anistreplase. The Third International Study of Infarct Survival (ISIS-3), a direct comparison of 3 thrombolytic agents (streptokinase, anistreplase, and duteplase), may provide some insight regarding the safety of these agents. Because these agents have been shown to be equally effective, selection of an appropriate agent for an individual patient may depend more on assessment of the likelihood of an adverse event or other factors, such as cost or convenience of administration, rather than assessment of the probability of greater benefit with a particular agent.     

Relation between infarct size and left ventricular performance assessed in patients with first acute myocardial infarction randomized to intracoronary thrombolytic therapy or to conventional treatment

Reperfusion of ischemic myocardium has been reported to increase the cumulative creatine kinase activity in plasma per gram of infarcted myocardium as assessed with the method of Shell et al. In an attempt to find out whether infarct size assessment using the method of Witteveen et al was affected by reperfusion, the relation between enzymatic infarct size was analyzed using Witteveen's method and left ventricular (LV) function parameters in 266 patients with first acute myocardial infarction randomized to intracoronary thrombolysis (n = 134) or conventional therapy (n = 132). Compared with patients allocated to conventional therapy, patients allocated to intracoronary thrombolysis had smaller enzymatic infarct size by 29% (p less than 0.001), smaller LV end-diastolic and end-systolic volume indexes by 10% (p less than 0.05) and 20% (p less than 0.005), respectively, and higher LV ejection fraction (55 +/- 1% vs 49 +/- 1%; p less than 0.001). The beneficial effects of thrombolytic therapy on LV performance were closely associated with thrombolysis-induced limitation of infarct size. The dependence from infarct size of LV end-diastolic volume, LV end-systolic volume, and ejection fraction was not different in the 2 therapy groups. It was concluded that Witteveen's method of infarct size assessment is not influenced by the presence of reperfusion. Therefore, this method was recommended for trials on recanalization in patients with acute myocardial infarction.     

Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.     

Acute coronary artery obstruction in myocardial infarction: overview of thrombolytic therapy

Pump failure, ranging from ventricular dysfunction to acute cardiogenic shock, is now the leading cause of cardiac death. Efforts at temporary mechanical or pharmacologic support of the heart have been largely unsuccessful so that attention is now directed toward prevention of ventricular failure and limitation of myocardial infarct size or even outright prevention of infarction itself. In particular, attention has been refocused on earlier reperfusion efforts with streptokinase. The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function and early mortality was studied in subsets of patients in a randomized trial (Netherlands Interuniversity Cardiology Institute). Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. Of the patients eligible for this detailed analysis, 245 were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiography was preformed in 212 of the 245 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 versus 1,179 U/liter in control subjects, p = 0.0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% versus 43% in control subjects, p = 0.0001). Twelve month mortality was lower in patients allocated to thrombolytic therapy (8% versus 16% in the control group, p less than 0.01). In multivariate regression analysis infarct size limitation, improvement of left ventricular ejection fraction and 3 month mortality were predicted by sigma ST, time from onset of symptoms to admission and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with a sigma ST segment of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function or mortality were observed in the subset of patients with sigma ST less than 1.2 mV, admitted 2 to 4 hours after onset of symptoms.     

Development and Pathophysiological Basis of Thrombolytic Therapy in Acute Myocardial Infarction: Part III, 1981–1985 Registries of Intracoronary Thrombolytic Therapy and Experimental Reperfusion Studies

The angiographic results of intracoronary thrombolysis were correlated with various outcome parameters in three registries. The West German Registry (n = 232) showed that mortality and improvement of left ventricular function were related to recanalization and prevention of reocclusion. This registry became the core database for the Food and Drug Administration (FDA) approval of thrombolytic agents for myocardial infarction in 1982. The European Registry (n = 414) analyzed changes in left ventricular ejection fraction further. A continuous model suggested that the functional benefit of reperfusion decreases rapidly and in a nonlinear fashion with delays in treatment during the first 3 hours. Reperfusion after > 6 hours was still associated with a significant benefit, which appeared to be related to collateral flow to the infarct zone. Myocardial salvage in experimental reperfusion studies and the reperfusion injury controversy are reviewed. In experimental studies performed by our group, it was found that thrombolytic agents did not exacerbate myocardial hemorrhage or increase infarct size. The Goettingen Registry (n = 152) demonstrated that reperfusion resulted in a steeper slope of the regression line between infarct size determined by ventriculography and cumulative serial creatine kinase release. Furthermore, reperfusion was associated with transient loss of R waves and transient development of Q waves. The implications of these findings regarding the reperfusion injury controversy and assessment of infarct size are discussed. Other analyses of the Goettingen data found that flow patterns to the infarct zone at preintervention angiography correlated with the duration of angina pectoris, incidence of antianginal therapy, and baseline ejection fraction. Assessment of the reliability of the admission ECG showed that half of the patients with infarction due to occlusion of the circumflex artery lacked diagnostic changes. The Goettingen Registery followed the first group of 70 patients ever treated with intracoronary thrombolytic therapy for 3 years. Mortality was low by the standards of the time. Reperfusion was associated with sustained improvement of left ventricular function and often dramatic clinical stabilization not seen before.     

Effect of reperfusion therapy for acute myocardial infarction on ventricular function and heart failure

Thrombolytic therapy reduces mortality and improves ventricular function in acute myocardial infarction. We review the short- and long-term effects of reperfusion after acute myocardial infarction on left ventricular function and heart failure. The beneficial effects of reperfusion may be achieved by immediate limitation of infarct size or through delayed improvement in ventricular remodeling. Infarct size is dependent on the area at risk, the time delay to reperfusion, the completeness and persistence of reperfusion, and collateral blood flow. The main prognostic parameters after myocardial infarction are vessel patency, infarct size, and ventricular volume and function. Initial infarct size and patency of the infarct-related artery are independent predictors of ventricular volume and function, as well as of survival in the long-term following acute myocardial infarction. The beneficial effects of a patent infarct-related artery are only evident if normal flow is achieved and maintained, and are dependent on the degrees of the residual stenosis. Thrombolytic therapy reduces the incidence of in-hospital congestive heart failure, and this improvement is sustained for at least 5 years. As only a fraction of patients with acute myocardial infarction currently receive thrombolytic therapy, heart failure after myocardial infarction can be reduced by administering thrombolytic therapy earlier to more patients with evolving acute myocardial infarction.     

Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction

This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery.     

Cost effectiveness of thrombolytic treatment for myocardial infarction: comparison of anistreplase, alteplase and streptokinase in 270 patients treated within 4 hours

Two hundred and seventy patients, under 71 years of age andsuffering from a less than 4 h infarction diagnosed accordingto clinical and electrocardiographic criteria, were included.two 90-patient groups were randomized and then treated witheither anistreplase (30 mg iv over 5 min) or alteplase (10 mgbolus injection + 5000 IU heparin bolus injection, followedby 90 mg alteplase over 3 h), and compared with a consecutivecontrol series of 90 patients treated with streptokinase (1.5million U over 1 h). Intravenous heparin and aspirin (250 mgday^–1) were then prescribed routinely. The three groupswere comparable as regards age (55.2±10 years), male/femaleratio (10.4 the site of the infarction (42% anterior, 55% inferior)and initial clinical seriousness (Killip I=90%, II=8%, III=2%).The patients were thombolysed in 17 community hospitals, andthen referred to a university hospital with catheterizationfacilities. An efficacy score was determined, based on fourparameters: two obtained from coronary angiography and leftventriculography performed on day 6±2 (N = 252) (asynergicscore and patency of the infarct-related artery), one from Tl-tomographyperformed at rest (infarct size) and one from radionuclide angiography(global left ventricular ejection fraction) performed betweenday 15 and day 21 (N = 242). The score (range: 0–24 perpatient) was 17.8±6.4 for alteplase, 17.7±6.0for anistreplase and 18.1±6.0 for streptokinase respectively(NS). The real cost of the hospital phase, for each patient,was determined by adding up the cost of thrombolytic treatment(ranging from 1.7% of the total hospital cost for streptokinaseto 16% for alteplase), other treatment and biological examinations(10% of the total cost), coronary angiography, followed in 35%of patients by angioplasty (21% of the overall cost) and hospitalization(ranging from 49% of the total cost for alteplase and anistreplaseto 56% for streptokinase [NS] for an average 17-day hospitalization.Thus, the total cost of the hospital phase was 6460 ECU foralteplase, 6570 ECU for anistreplase and 6050 ECU for streptokinase(NS). The cost/efficacy ratio was 548 ECU for alteplase, 570ECU for anistreplase and 405 ECU for streptokinase. Secondarymortality and re-infarction rates were very low (1.2% and 1.5%respectively) after 1 year following the treatment. However,ischaemia recurred in 23% of patients, requiring revascularizationoperations in 9% of them. Sixty-nine per cent of patients withprofessional occupations were able to resume these activities. This study showed no difference in efficacy between the threethrombolytic agents for the three left ventricular parameters(left ventricular ejection fraction, asynergic score, necroticmass) and for the patency of the infarct-related artery, andalso demonstrated that the cost of the thrombolytic agent hadrelatively little effect on the total cost of myocardial infarction.There could be a potential saving by shortening hospitalization,which accounted for half the cost of thrombolysed myocardialinfarction.     

Plasma levels of neuropeptide Y i patients with current myocardial infarction

Neuropeptide Y (NPY) has been recently characterised as one of the strongest circulating vasoconstrictor peptides, its elevated level may cause coronary artery spasm and increase of peripheral vascular resistance. All this contributes to ischemic myocardial damage and decrease of regional and global left ventricular function. The aim of the study was the examination of NPY plasma levels in patients with acute myocardial infarction (AMI) after thrombolytic therapy with or without reperfusion. The survey was made in 82 patients with AMI after thrombolytic therapy: 40 of them without reperfusion and 42 with reperfusion. The control group consisted of 20 healthy persons. Plasma levels of NPY were measured before thrombolysis, then 1, 3 and 5 days after, using a radioimmunologic method. All patients were treated with aspirin, glyceryl trinitrate and thrombolytic therapy (TT) with alteplase (r-TPA). In patients with AMI, NPY plasma levels were normal before and 1 day after TT, and were significant elevated 3 days after TT 5 days after TT, plasma NPY levels were still high in patients without reperfusion, but they decreased in patients with reperfusion. There was significant negative correlation between NPY level and left ventricular ejection fraction measured 5 days after AMI. During 30-days follow up systolic dysfunction of left ventricle with ejection fraction under 40% occurred in 21 patients and in 11 of them clinical symptoms of heart failure were observed. Using the multivariable regression analysis we showed that NPY concentration over 60 pg/ml is the independent factor leading to left ventricle systolic dysfunction. The results of our study suggest the contribution of NPY to the left ventricular remodeling after AMI.     

Are the various thrombolytic agents equally effective in the treatment of acute transmural myocardial infarction?

While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint.     

Reliability of Q-wave formation and QRS score in predicting regional and global left ventricular performance in acute myocardial infarction with successful reperfusion

The frequency of electrocardiographic Q-wave formation and the relation of Q wave and QRS score to regional and global left ventricular (LV) performance were determined in 131 patients with acute myocardial infarction (AMI) receiving thrombolytic therapy. Thrombolytic therapy was successful in reperfusing the occluded infarct artery in 100 patients and was unsuccessful in 31. The number of patients who had 1 or more Q waves (88 vs 87%) and 2 or more Q waves (70 vs 74%) was similar. In contrast, normal wall motion was significantly more common in the infarct area in patients in whom reperfusion was successful (42 vs 15%, p less than 0.05). Total QRS scores were similar in patients in whom reperfusion was successful and in those in whom it was not (6.0 +/- 3.2 vs 6.4 +/- 4.2). Despite similar QRS scores, successfully treated patients had significantly higher LV ejection fraction (53 +/- 13% vs 46 +/- 15%, p less than 0.05). Thus, Q-wave formation after successful thrombolytic therapy for AMI is common but does not faithfully reflect regional or global LV performance. Electrocardiographic analysis alone is not a reliable method to assess efficacy of reperfusion therapy.     

Long-term prognosis of late spontaneous reperfusion after failed thrombolysis for acute myocardial infarction

BACKGROUND: Early reperfusion improves left ventricular (LV) function and survival after acute myocardial infarction (MI). Thrombolytic therapy achieves early patency of the infarct artery in about two-thirds of patients. In nearly half of the remaining patients, in whom early reperfusion was not achieved with thrombolytic therapy, the infarct artery might reopen by the time of predischarge angiography. However, the impact of such late spontaneous reperfusion after failed thrombolytic therapy on LV function and long-term survival remained unclear. HYPOTHESIS: This study was undertaken to assess implication of late spontaneous reperfusion after failed thrombolytic therapy on LV function and long-term survival after acute MI. METHODS: The study consisted of 198 patients with anterior acute MI who underwent thrombolytic therapy and predischarge angiography: 160 patients with infarct artery patent early and late after therapy (persistent patency), 17 patients with infarct artery occluded early after therapy but patent at predischarge angiography (late spontaneous reperfusion), and 21 patients with infarct artery occluded early and late after therapy (persistent occlusion). RESULTS: Persistent patency was associated with enhanced improvement in LV ejection fraction (7.7 +/- 11.8%) compared with late spontaneous reperfusion (0.0 +/- 9.6%, p = 0.03) and persistent occlusion (-1.4 +/- 9.7%, p = 0.003). Persistent patency was associated with better long-term survival than with late spontaneous reperfusion (p < 0.001) and persistent occlusion (p < 0.001). Multivariate analysis comparing persistent patency and late spontaneous reperfusion showed that early reperfusion was an independent predictor of long-term survival. CONCLUSION: Late spontaneous reperfusion after failed thrombolytic therapy was associated with poor LV function and long-term survival, emphasizing the importance of early reperfusion.     

Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators

BACKGROUND. The influence of coronary collateral vessels on infarct size in humans remains controversial, partly because no previous study has examined the impact of collaterals present at the onset of acute myocardial infarction on infarct size. METHODS AND RESULTS. The present study used the data base of the Thrombolysis in Myocardial Infarction (TIMI) Phase I trial to correlate the presence or absence of angiographically documented collaterals in the initial hours of myocardial infarct evolution with the size of the infarct as assessed by serial measurements of serum creatine kinase (CK). To avoid the confounding effects of reperfusion on enzymatic estimates of infarct size, this report is limited to those 125 patients who failed to recanalize at 90 minutes after administration of tissue plasminogen activator or streptokinase. Patients with angiographically documented collaterals (group A, n = 51) had significantly lower values of peak serum CK than patients without collaterals (group B, n = 74) (1,877 +/- 216 versus 2,661 +/- 212 IU/l, respectively [mean +/- SEM], p = 0.004). Similarly, CK-derived infarct size estimates were significantly lower in group A than in group B (20.6 +/- 2.5 versus 31.4 +/- 2.8 CK gram equivalents, p = 0.001). The infarct size observed in patients with collaterals was less for anterior infarctions as well as for infarctions of other locations; thus, the beneficial effects of collaterals were independent of the site of the infarct. In 65 of the 125 patients who failed to reperfuse, left ventricular ejection fraction (LVEF) was assessed by contrast ventriculography both at initial cardiac catheterization (before thrombolytic therapy) and at hospital discharge. Among the patients who had both studies, global LVEF tended to increase from pretreatment to hospital discharge in group A (from 50.6 +/- 1.8% to 53.4 +/- 1.8%, p = 0.10) but decreased in group B patients (from 50.3 +/- 1.8% to 47.8 +/- 1.7%, p = 0.02). At hospital discharge, global LVEF was greater in patients with coronary collaterals (53.5 +/- 1.7% versus 49.6 +/- 1.7%, p = 0.01). CONCLUSIONS. The results demonstrate that, in patients in whom thrombolytic therapy fails to induce reperfusion, the presence of coronary collateral vessels at the onset of myocardial infarction is associated with limitation of infarct size as assessed enzymatically and with improved ventricular function on discharge as assessed by LVEF.     

Echocardiographic determinants of left ventricular ejection fraction after acute myocardial infarction

OBJECTIVE: This study was performed to determine if factors other than the size of regional dysfunction influence the global left ventricular ejection fraction after acute myocardial infarction. BACKGROUND: Left ventricular ejection fraction is an important prognostic variable after acute myocardial infarction. Although infarct size is known to affect the subsequent global left ventricular ejection fraction, it remains unclear whether other factors such as site or severity of the wall motion abnormality influence the ejection fraction after acute myocardial infarction. METHODS: Sixty-nine consecutive patients (mean age 61 +/- 14 years, 46 [67%] male) who did not receive thrombolytic therapy or undergo early revascularization were studied by echocardiography 1 week after Q-wave myocardial infarction. The absolute size of the region of abnormal wall motion (AWM) and the percentage of the endocardium involved (%AWM) were quantitated along with the wall motion score. A severity index was then derived as the mean wall motion score within the region of AWM. Site of myocardial infarction was classified as either anterior or inferior from the endocardial map. Left ventricular ejection fraction was measured by Simpson's method with 2 apical views. RESULTS: Twenty-nine (42%) patients had anterior and 40 had inferior myocardial infarction. The mean left ventricular ejection fraction was significantly lower in anterior than in inferior myocardial infarction (44.8% +/- 11.5% vs 53% +/- 8.6%; P =. 001). The mean %AWM was greater in anterior than in inferior myocardial infarction (32.1 +/- 15.5 vs 22.4 +/- 14.1; P =.01). The mean wall motion score was greater in anterior than in inferior myocardial infarction (9.8 +/- 6.4 vs 6.4 +/- 4.4; P =.01). The mean severity index did not differ by site. Multiple regression analysis demonstrated that, in descending order of importance, %AWM, extent of apical involvement, and site of myocardial infarction were independent determinants of global left ventricular ejection fraction. CONCLUSIONS: For myocardial infarctions of similar size, left ventricular ejection fraction is lower when apical involvement is extensive and the site of infarction is anterior. This site-dependent difference may be related to characteristics specific to the apex.     

Significance of preinfarction angina for preservation of left ventricular function in acute myocardial infarction.

The effect of preinfarction angina on the preservation of left ventricular function was evaluated with the use of cineventriculography in 37 patients who had either total or subtotal occlusion of the proximal left anterior descending coronary artery during the convalescent period of myocardial infarction. In 15 patients who had preinfarction angina more than 1 week before the onset of acute myocardial infarction (group A), the global left ventricular ejection fraction was 54 +/- 3% (SEM) and regional wall motion in the infarct area was 10 +/- 3%. In 10 patients who had preinfarction angina occurred within 1 week before the onset of acute myocardial infarction (group B), the left ventricular ejection fraction and regional wall motion in the infarct area were 42 +/- 3% and 1 +/- 2%, respectively. In 12 patients without preinfarction angina (group C), the left ventricular ejection fraction and regional wall motion in the infarct area were 38 +/- 3% and -1 +/- 2%, respectively. In groups B and C, both the left ventricular ejection fraction and regional wall motion in the infarct area were lower than those in group A (p less than 0.05). The collateral circulation at the onset of acute myocardial infarction was better in group A compared with groups B and C (p less than 0.05). Thus the collateral circulation, promoted by repetitive anginal episodes indicative of myocardial ischemia, causes the preservation of myocardial function.     

Which patients benefit most from early thrombolytic therapy with intracoronary streptokinase?

The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function, and early mortality was studied in subsets of patients in a randomized trial. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hr after onset of symptoms indicative of acute myocardial infarction. Four hundred eighty-eight patients were eligible for this detailed analysis, and 245 of these were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiographic examinations were performed in 212 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, as measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 vs 1170 U/liter in control patients, p = .0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge from the hospital was higher after thrombolytic therapy (median 50% vs 43% in control patients, p = .0001). Three month mortality was lower in patients allocated to thrombolytic therapy (6% vs 14% in the control group, p = .006). With the use of multivariate regression analysis, infarct size limitation, improvement in left ventricular ejection fraction, and three month mortality were predicted by sum of the ST segment elevation, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most effective in patients admitted within 2 hr after onset of symptoms and in patients with a sum of ST segment elevation of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function, or mortality were observed in the subset of patients with a sum of ST segment elevation of less than 1.2 mV who were admitted between 2 and 4 hr after onset of symptoms.     

Comparison of radionuclide and enzymatic estimate of infarct size in patients with acute myocardial infarction

A comparison was made of the estimated size of the myocardial infarction occurring in 26 patients with a first infarction using creatine kinase (CK) enzyme release between radionuclide gated blood pool measurement of total and regional ventricular function and thallium-201 scintigraphic measurement of myocardial perfusion defects. Creatine kinase estimates of infarct size (enzymatic infarct size) correlated closely with the percent of abnormal contracting regions, left ventricular ejection fraction and thallium-201 estimates of percent of abnormal perfusion area (r = 0.78, 0.69 and 0.74, respectively, p less than 0.01). A close correlation also existed between percent abnormal perfusion area and percent of abnormal contracting regions (r = 0.81, p less than 0.01) and left ventricular ejection fraction (r = 0.69, p less than 0.01). Enzymatic infarct size was larger in anterior (116 +/- 37 CK-g-Eq) than inferior (52 +/- 29 CK-g-Eq) myocardial infarction (p less than 0.01) and was associated with significantly more left ventricular functional impairment as determined by left ventricular ejection fraction (33 +/- 7 versus 60 +/- 10%) (p less than 0.01) and percent abnormal perfusion area (58 +/- 14 versus 13 +/- 12) (p less than 0.01). No significant correlation was observed between enzymatic infarct size and right ventricular ejection fraction. These different methods of estimating infarct size correlated closely with each other in these patients with a first uncomplicated myocardial infarction.