Rosemary A. Hackworthy

Infarct artery perfusion and changes in left ventricular volume in the month after acute myocardial infarction

The relation between perfusion of the infarct-related artery and changes in left ventricular volume and function during the month after a first myocardial infarction was examined in 40 patients who did not receive thrombolytic therapy. Infarct artery perfusion was documented at predischarge coronary angiography, and left ventricular volume was measured by nongeometric analysis of radionuclide angiograms performed within 48 hours of infarction and at 1 month. Left ventricular dilation (greater than or equal to 20% increase in volume) developed in 16 patients, whereas 5 patients had a decrease in left ventricular volume of greater than or equal to 20% by 1 month. Left ventricular dilation occurred in all 14 patients without perfusion of the infarct-related artery, compared with only 2 of 26 patients with perfusion of this artery due to subtotal occlusion or collateral vessels. All five patients whose left ventricular volume decreased by greater than or equal to 20% had a perfused infarct artery. Multiple linear regression analysis confirmed that the degree of perfusion of the infarct artery (partial r = 0.58, p = 0.001) was a more important predictor of volume change than was infarct size measured by peak creatine kinase (partial r = 0.30, p = 0.009) or QRS score (partial r = 0.20, p = 0.087). Left ventricular ejection fraction decreased from 0.38 +/- 0.10 to 0.30 +/- 0.16 (p = 0.05) in 11 patients with an anterior infarct and ventricular dilation; it increased from 0.45 +/- 0.10 to 0.62 +/- 0.07 (p = 0.02) in the 5 patients with a greater than or equal to 20% decrease in volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: Controlled comparison with intracoronary streptokinase

The recent establishment of a firm therapeutic role for reperfusion in acute myocardial infarction has stimulated interest in the development of more ideal thrombolytic agents. Anisoylated plasminogen streptokinase activator complex (APSAC) is a new plasminogen activator possessing properties that are promising for intravenous thrombolytic application in acute myocardial infarction. To assess the reperfusion potential of intravenous APSAC, a multi-center, angiographically controlled reperfusion trial was performed. An approved thrombolytic regimen of intracoronary streptokinase served as a control. Consenting patients with clinical and electrocardiographic signs of acute myocardial infarction were studied angiographically and 240 qualifying patients with documented coronary occlusion (flow grade 0 or 1) were randomized to treatment in less than 6 h of symptom onset (mean 3.4 h, range 0.4 to 6.0) with either intravenous APSAC (30 U in 2 to 4 min) or intracoronary streptokinase (160,000 U over 60 min). Both groups also received heparin for greater than or equal to 24 h. Reperfusion was evaluated angiographically over 90 min and success was defined as advancement of grade 0 or 1 to grade 2 or 3 flow. Rates of reperfusion for the two treatment regimens were 51% (59 of 115) at 90 min after intravenous APSAC and 60% (67 of 111) after 60 min of intracoronary streptokinase (p less than or equal to 0.18). Reperfusion at any time within the 90 min was observed in 55 and 64%, respectively (p less than or equal to 0.16). Time to reperfusion occurred at 43 +/- 23 min after intravenous and 31 +/- 17 min after intracoronary therapy. The success of intravenous therapy was dependent on the time to treatment: 60% of APSAC patients treated within 4 h exhibited reperfusion compared with 33% of those treated after 4 h (p less than or equal to 0.01). Reperfusion rates were also dependent on initial flow grade (p less than or equal to 0.0001): 48% (81 of 168) for grade 0 (APSAC = 43%, streptokinase = 54%), but 78% for grade 1 (APSAC = 78%, streptokinase = 77%). APSAC given as a rapid injection was generally well tolerated, although the median change in blood pressure at 2 to 4 min was greater after APSAC than after streptokinase (-10 versus -5 mm Hg). Mean plasma fibrogen levels fell more at 90 min after the sixfold higher dose of APSAC than after streptokinase (to 32 versus 64% of control). Reported bleeding events were more frequent after APSAC but occurred primarily at the site of catheter insertion and no event was intracranial.(ABSTRACT TRUNCATED AT 400 WORDS)

Multicenter patency trial of intravenous anistreplase compared with streptokinase in acute myocardial infarction. The TEAM-2 Study Investigators.

Thrombolytic therapy has been shown to improve clinical outcome when administered early aftertheonsetofsymptomsofacutemyocardialinfarction;themechanismofbenefitisbelieved to be reestablishment and maintenance ofcoronaryartery patency. Anistreplase is a second generationthrombolyticagentthatiseasilyadministered andhas alongdurationofaction. To compareanistreplase (30units/2-5min)andtherapywiththeFoodandDrugAdministration-approved regimen ofintravenous streptokinase (1.5 million units/60 mmn), a randomized, double-blind, multicenterpatencytrialwasundertakenin370patientslessthan76yearsofage withelectrocardiographic STsegmentelevationwhocouldbetreatedwithin4hoursofsymptom onset. Coronarypatencywasdeterminedbyreading, inablindedfashion, angiograms obtained early (90–240 minutes; mean, 140 minutes) and later (18–48 hours; mean, 28 hours) after beginning therapy. Early total patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion) was high after both anistreplase (132/183=72%) and streptokinase (129/176=73%) therapy, and overall patency patterns were similar, although patent arteries showed “complete” (grade3) perfusion moreoftenafteranistreplase (83%) than streptokinase (72%) (p = 0.03). Similarly, residualcoronarystenosis, determinedquantitativelybyavalidated computer-assisted method, was slightly less in patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than streptokinase (77.2%, p = 0.02). In patientswith patent arteries withoutotherearlyinterventions, reocclusionriskwithin1-2dayswasdefinedangiographically andfoundtobeverylow (anistreplase=1/96, streptokinase=2/94). Averagecoronaryperfusion gradewasgreater, andpercentresidualstenosiswasless, atfollow-upthanoninitialevaluation anddidnotdifferbetweentreatmentgroups. Enzymaticandelectrocardiographicevolutionwas not significantly different in the two groups. Despite rapid injection, anistreplase was associated with only a small (4–5 mmHg), transient (at 5–10 minutes) mean differential fall in bloodpressure. In-hospital mortalityrates were comparable foranistreplase and streptoki-nase (5.91%, 7.1%). Stroke occurred in one (0.5%) and three (1.6%) patients, respectively; one stroke was hemorrhagic. Other serious bleeding events and adverse experiences occurred uncommonlyandwithsimilarfrequencyinthetwogroups. Thus, fortheendpointsofourstudy (patency, safety), anistreplase and streptokinase showed overall favorable and relatively comparable outcomes, with a few differences. When given to patients within 4 hours from onsetofsymptoms ofacutemyocardialinfarction, boththrombolytic agents established high and similar total patency rates within a mean of 2.4 hours after therapy, although quantitative residual stenosis was slightly less early after anistreplase. The clinical importance ofthese orother differences, such as ease ofdrugadministration, are uncertain but will be answered by ongoing comparative mortality studies and by broader clinical experience. In the interim, these data support the continued use ofboth ofthese agents in acute myocardial infarction.

Effect of reperfusion on electrocardiographic and enzymatic infarct size: results of a randomized multicenter study of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) versus intracoronary streptokinase in acute myocardial infarction

The effect of early coronary artery reperfusion on ECG and enzymatic parameters was examined in 240 patients with acute myocardial infarction. These patients had participated in a randomized trial comparing intravenous anisoylated plasminogen streptokinase activator complex (APSAC) (n = 123) and intracoronary streptokinase (n = 117) therapy. Reperfusion occurred in 59 of 115 (51%) patients receiving APSAC and 67 of 111 (60%) patients receiving streptokinase (p = NS). There was greater early resolution of ST segment elevation in the reperfused than in the nonreperfused patients (p less than or equal to 0.003) and more rapid Q wave evolution (p less than or equal to 0.03). Sigma Q was lower in reperfused than in nonreperfused patients at 8 hours (1.41 +/- 1.18 versus 2.11 +/- 2.10 mV; p less than or equal to 0.05) and at 24 hours (1.43 +/- 1.25 mV versus 2.08 +/- 1.88 mV; p less than or equal to 0.02). Time to peak level was shorter in the reperfused patients for creatine kinase (CK) (10.7 +/- 5.5 hours versus 14.9 +/- 5.9 hours; p less than 0.0001) and lactic acid dehydrogenase (LDH) (29.6 +/- 13.6 hours versus 34.4 +/- 10.5 hours; less than or equal to 0.03) enzymes. Peak LDH-1 was lower in the reperfused group (274 +/- 149 U/L versus 341 +/- 173 U/L; p less than or equal to 0.04). Reperfusion at a mean of 3.9 hours after the onset of infarction was associated with more rapid resolution of ST segment elevation, faster Q wave evolution, smaller ECG infarct size, earlier cardiac enzyme release, and smaller enzymatic infarct size than later or no reperfusion.

Dependence of assessment of coronary artery reperfusion during acute myocardial infarction on angiographic criteria and interobserver variability

The angiographic films of 240 patients with acute myocardial infarction were studied in a randomized trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) versus intracoronary streptokinase therapies. The interobserver variability of grading coronary artery perfusion by the Thrombolysis in Myocardial Infarction Study Group (TIMI) criteria was measured as well as the effect of different definitions of reperfusion on the determination of reperfusion rate. There was good agreement in the reading of infarct artery flow grades between 2 blinded observers for each grade considered separately (k = 0.726 +/- 0.014) and for grades 0 or 1 (no perfusion) versus grades 2 or 3 (perfusion) (k = 0.905 +/- 0.011). Discordance between grades 0 or 1 versus 2 or 3 occurred in 74 (5%) of the 1,615 angiographic readings. Discrepancies of clinical significance which affected qualification for study entry, reperfusion or reocclusion status occurred in only 15 patients (6%). Grade 1 flow was found to have the most variable interpretation. Reperfusion rates for APSAC and streptokinase differed significantly when reperfusion was defined by 3 different criteria. The reperfusion rate ranged from 51 to 72% for APSAC and from 60 to 75% for streptokinase depending upon criteria selected. For comparison of the results of different thrombolytic studies, a standard semiquantitative system for grading infarct artery perfusion should be used, readings should be blinded and the criteria used for the definition of reperfusion should be clearly specified.

Relation of plasma D-dimer concentrations to coronary artery reperfusion before and after thrombolytic treatment in patients with acute myocardial infarction☆

This study was designed to investigate the possible role of pre- and posttreatment plasma D-dimer concentration as a reflection of coronary artery thrombolysis. Blood was collected from 206 patients with angiographically documented acute coronary occlusion presenting within 6 hours of symptom onset who were enrolled in a prospective study comparing intravenous APSAC (30 U) (IV-APSAC) with intracoronary streptokinase (160,000 U) (IC-SK). D-dimer concentrations in 104 patients after IV-APSAC therapy were higher than in 90 patients after IC-SK (mean +/- standard error, 1,009 +/- 60 vs 603 +/- 45, p less than 0.001), but there was no difference in patients with and without reperfusion (1,096 +/- 88 vs 875 +/- 67, p = 0.1 for IV-APSAC, and 587 +/- 48 vs 634 +/- 95, p = 0.6 for IC-SK). The median concentrations before treatment were similar in the IV-APSAC and IC-SK groups (93 and 90 ng/ml, respectively). These were higher than the value in 25 ambulatory control subjects (72 ng/ml) but lower than in 29 post-AMI (6 to 30 hours) patients and in preoperative orthopedic patients (140 ng/ml each). There was no difference in D-dimer concentrations in patients with grade 0 or grade 1 coronary artery occlusion (median 85 vs 90 ng/ml) or in patients with or without ultimate successful reperfusion (median 85 vs 93 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic and Enzymatic Infarct Size in a Randomised Study of Intracoronary Streptokinase and Intravenous Anisoylated Plasminogen Streptokinase Activator Complex in Acute Myocardial Infarction

SummaryThe effect of thrombolytic therapy on ECG and enzymatic indices, including estimates of relative infarct size, was studied in 93 patients with acute myocardial infarction randomised to intracoronary streptokinase or intravenous anisoylated plasminogen streptokinase activator complex (APSAC) therapy within 6 hours of the onset of symptoms. 90 minutes after treatment, 49% (19/39) of the evaluable streptokinase patients and 44% (19/43) of the APSAC patients had reperfused (p = NS). The time from treatment to reperfusion was less in the streptokinase patients (30 ± 18 minutes for streptokinase and 42 ± 22 minutes for APSAC, p ⩽ 0.02). Resolution of ST segment elevation, 90 minutes after treatment, was greater in the streptokinase patients (residual ST segment elevation 47 ± 36% of initial value for streptokinase and 70 ± 49% for APSAC, p ⩽ 0.06) and in the patients reperfused by either agent (residual ST segment elevation 46 ± 34% for reperfused and 68 ± 52% for non-reperfused, p ⩽ 0.10). ECG infarct size at discharge, determined by sum of Q waves and a 29-point QRS score, relative to the degree of initial ST segment elevation was similar in the streptokinase and APSAC patients, but smaller in reperfused than non-reperfused patients (p ⩽ 0.01 for ΣQ). Peak serum creatine kinase and MB isoenzyme of creatine kinase levels were similar in the streptokinase and APSAC, and in reperfused and non-reperfused patients. Lower peak lactic acid dehydrogenase and especially lactic acid dehydrogenase isoenzyme values (by 16% and 22%, respectively) were observed in reperfused patients, but differences did not achieve significance. However, the time to peak enzyme levels was significantly shorter in the reperfused patients. Early intracoronary streptokinase and intravenous APSAC therapy have similar effects on ECG and enzymatic infarct size. Reperfusion by either agent, given at a mean of 3 hours 25 minutes, may reduce estimates of infarct size modestly.

Acute Coronary Occlusion and Reperfusion

Summary93 patients with acute myocardial infarction entered into a multicentre, randomised fibrinolytic therapy study underwent coronary angiography prior to treatment with intracoronary streptokinase or intravenous anisoylated plasminogen streptokinase activator complex (APSAC). Subsequent to administration of fibrinolytic therapy, coronary arteriography of the infarct-related artery was also performed at 15, 30, 45, 60, 75 and 90 minutes. Angiographically defined coronary perfusion was graded as follows: grade 0 — no perfusion; grade 1 — vessel penetration by contrast without perfusion; grade 2 — partial perfusion with delayed flow and/or clearance; grade 3 — normal flow and clearance.Two independent readers at separate sites reviewed all serial angiograms with consensus achieved with a third reader. Disagreement potentially affecting therapeutic outcome (grades 1 vs 2, 0 vs 2, 0 vs 3, and 1 vs 3) occurred for only 15 angiographic views. Evaluation of agreement by the K index demonstrated a reasonable level of agreement for all grades (K = 0.73).In order to assess the effect of angiographic classification and timing upon reperfusion percentage rates, 4 reperfusion criteria were applied to these serial angiograms: group A = grade 2 or 3 flow at 90 minutes; group B = grade 2 or 3 flow at any time; group C = grade 1, 2 or 3 flow at any time in patients with control grade 0 or 1 flow; group D = grade 1, 2 or 3 flow at any time in patients with only grade 0 flow at control. Percentage reperfusion varied widely depending upon reperfusion criteria: group A: streptokinase 49%, APSAC 44%; group B: streptokinase 70%, APSAC 50%; group C: streptokinase 86%, APSAC 67%; group D: streptokinase 79%, APSAC 59%.We conclude that coronary artery angiographic perfusion may be reliably and reproducibly evaluated using semiquantitative grading techniques, but that coronary artery reperfusion rates for streptokinase may vary from 49% to 86% solely depending on the angiographic criteria of reperfusion.