Fidela Moreno

Reduction in QT interval dispersion by successful thrombolytic therapy in acute myocardial infarction. TEAM-2 Study Investigators.

QT dispersion (QTd, equals maximal minus minimal QT interval) on a standard ECG has been shown to reflect regional variations in ventricular repolarization and is significantly greater in patients with than in those without arrhythmic events. Methods and ResultsTo assess the effect of thrombolytic therapy on QTd, we studied 244 patients (196 men; mean age, 57±10 years) with acute myocardial infarction (AMI) who were treated with streptokinase (n= 115) or anistreplase (n=129) at an average of 2.6 hours after symptom onset. Angiograms at 2.4±1 hours after thrombolytic therapy showed reperfusion (TIMI grade ≥ 2) in 75% of patients. QT was measured in 10±2 leads at 9±5 days after AMI by using a computerized analysis program interfaced with a digitizer. QTd, QRSd, JT (QT minus QRS), and JT dispersion (JTd, equals maximal minus minimal JT interval) were calculated with a computer. There were significant differences in QTd (96±31, 88±25, 60±22, and 52±19 milliseconds; P < .0001) and in JTd (97±32, 88±31, 63±23, and 58±21 milliseconds; P = .0001) but not in QRSd (25±10, 22±7, 28±9, and 24±9 milliseconds; P = .24) among perfusion grades 0, 1, 2, and 3, respectively. Similar results were obtained comparing TIMI grades 0/1 with 2/3 and 0/1/2 with 3. Patients with left anterior descending (versus right and left circumflex) coronary artery occlusion showed significantly greater QTd (70±29 versus 59±27 milliseconds, P = .003) and JTd (74±30 versus 63±27 milliseconds, P = .004). Similarly, patients with anterior (versus inferior/lateral) AMI showed significantly greater QTd (69±30 versus 59±27 milliseconds, P = .006) and JT d (73±30 versus 63±27 milliseconds, P = .007). Results did not change when Bazetts QTc, or JTc, was substituted for QT or JT or when ANOVA included adjustments for age, sex, drug assignment, infarct site, infarct vessel, and number of measurable leads. On ANCOVA, the relation of QTd or JTd and perfusion grade was not influenced by heart rate. ConclusionsSuccessful thrombolysis is associated with less QTd and JTd in post-AMI patients. The results are equally significant when either QT or JT is used for analysis. These data support the hypothesis that QTd after AMI depends on reperfusion status as well as infarct site and size. Reduction in QTd and its corresponding risk of ventricular arrhythmia may be mechanisms of benefit of thrombolytic therapy.

Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study

One measure of the success of thrombolysis is the early patency status of the infarct-related coronary artery. The Thrombolysis in Myocardial Infarction (TIMI) study group designated patency grades 0 (occluded) or 1 (minimal perfusion) as thrombolysis failure and grade 2 (partial perfusion) or 3 (complete perfusion) as success. To evaluate their true functional significance, perfusion grades were compared with enzymatic and electrocardiographic (ECG) indexes of myocardial infarction in 359 patients treated within 4 h with anistreplase (APSAC) or streptokinase. Serum enzymes and ECGs were assessed serially. Patency was determined at 90 to 240 min (median 2.1 h) and graded by an observer who had no knowledge of patient data. Results for the two drug arms were similar and combined. Distribution of patency was grade 0 = 20%, n = 72; grade 1 = 8% n = 27; grade 2 = 16%, n = 58 and grade 3 = 56%, n = 202. Interventions were performed after angiography but within 24 h in 51% (n = 37), 70% (n = 19), 41% (n = 24) and 14% (n = 28) of patients with grades 0, 1, 2 and 3, respectively. Outcomes were compared among the four patency groups by the orthogonal contrast method. Patients with perfusion grade 2 did not differ significantly from those with grade 0 or 1 in enzymatic peaks, time to peak activity and evolution of summed ST segments, Q waves and R waves (contrast 2). Conversely, comparisons of patients with grade 3 perfusion with those with grades 0 to 2 yielded significant differences for enzymatic peaks and time to peak activity for three of the four enzymes (p = 0.02 to 0.0001) and ECG indexes of myocardial infarction (p = 0.02 to 0.0001) (contrast 3). Thus, patients with grade 2 flow have indexes of myocardial infarction similar to those in patients with an occluded artery (grades 0 and 1 flow). Only early grade 3 flow results in a significantly better outcome than that of the other grades. Because early achievement of grade 2 flow does not appear to lead to optimal myocardial salvage, the frequency of achieving grade 3 perfusion alone may best measure the reperfusion success of thrombolytic therapy.

Evaluation of size and dynamics of the inferior vena cava as an index of right-sided cardiac function.

To define normal criteria of size and dynamics of the inferior vena cava (IVC) and its clinical value in assessing right-sided cardiac function, 2-dimensional (2-D) and M-mode echocardiography (echo) were performed in 175 subjects, who were classified into 3 groups: group 1-80 normal subjects; group IIA--65 patients with documented right-sided cardiac disease, and group IIB--30 patients with cardiac disease but no right-sided abnormality. The IVC was adequately imaged in 175 of 185 subjects (95%). There was good correlation between M-mode and 2-D echo (r = 0.84) and long- and short-axis (r = 0.88) measurements. The IVC diameter during expiration was: group 1-9 to 28 mm (mean 18.2 +/- 4.6); group IIA--15 to 40 mm (mean 23.1 +/- 4.8) and group IIB-8-24 mm (mean 15.6 +/- 3.7). Collapsibility index (inspiratory decrease in diameter) was: group I-37 to 100% (mean 55.8 +/- 15.9); group IIA--0 to 39% (mean 13.5 +/- 10.5); and group IIB--44 to 100% (mean 60.4 +/- 13.1). A and V waves could be measured in 120 of 151 cases (79%). Both A and V waves were less than 125% of its diameter in group I. The A wave was absent in 34 patients; 30 (88%) were in atrial fibrillation. Among 8 patients with tricuspid regurgitation, 5 (63%) had V waves greater than 125%. There was no correlation between diameter or collapsibility index and age, sex, rhythm or body surface area.(ABSTRACT TRUNCATED AT 250 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.

Multivariate associates of QT dispersion in patients with acute myocardial infarction : Primacy of patency status of the infarct - related artery.

BACKGROUND QT dispersion (QTd; QT interval maximum minus minimum) has been shown to reflect regional variations in ventricular repolarization and is increased in patients with life-threatening ventricular arrhythmias. METHODS To determine correlates of QTd in patients who had had myocardial infarction (MI), 207 patients (158 men, aged 57 +/- 11 years) with acute MI who were treated with alteplase or anistreplase within 2.7 +/- 0.9 hours of symptom onset were studied. Angiograms at a median of 27 hours after thrombolysis showed reperfusion (Thrombolysis in Myocardial Infarction grade > or =2) in 184 (88%) patients. QT was measured in 10 +/- 2 leads on discharge electrocardiograms with a computerized analysis program interfaced with a digitizer. Associations of QTd with 24 variables related to patient characteristics, acute MI, angiography, interventions, and radionuclide ventriculography were evaluated by univariate and multivariate regression. RESULTS Univariate associations with QTd (p < or = 0.10) were Thrombolysis in Myocardial Infarction flow grade 0/1 versus 2/3 (QTd = 75 +/- 33 msec vs 53 +/- 22 msec, p < 0.0001), minimal luminal diameter (p = 0.007), left ventricular ejection fraction at discharge (p = 0.007), reinfarction (p = 0.01), number of leads with ST elevation (p = 0.05), end-systolic volume at discharge (p = 0.04), time to peak creatine kinase (p = 0.06), and YST elevation (p = 0.10). Independent associates of QTd were Thrombolysis in Myocardial Infarction grade 0/1 versus 2/3 (p < 0.0001), reinfarction (p = 0.005), and ejection fraction (p = 0.02). CONCLUSIONS Successful thrombolysis is associated with less QTd in patients after acute MI. Our results support the hypothesis that QTd after MI depends on reperfusion status, reinfarction, and left ventricular function. Reduction in QTd may be an additional mechanism by which the benefit of thrombolytic therapy is realized.

Anistreplase versus alteplase in acute myocardial infarction: Comparative effects on left ventricular function, morbidity and 1-day coronary artery patency

OBJECTIVES This double-blind, randomized, multicenter trial was designed to compare the effects of treatment with anistreplase (APSAC) and alteplase (rt-PA) on convalescent left ventricular function, morbidity and coronary artery patency at 1 day in patients with acute myocardial infarction. BACKGROUND Anistreplase (APSAC) is a new, easily administered thrombolytic agent recently approved for treatment of acute myocardial infarction. Alteplase (rt-PA) is a rapidly acting, relatively fibrin-specific thrombolytic agent that is currently the most widely used agent in the United States. METHODS Study entry requirements were age less than or equal to 75 years, symptom duration less than or equal to 4 h, ST segment elevation and no contraindications. The two study drugs, APSAC, 30 U/2 to 5 min, and rt-PA, 100 mg/3 h, were each given with aspirin (160 mg/day) and intravenous heparin. Prespecified end points were convalescent left ventricular function (rest/exercise), clinical morbidity and coronary artery patency at 1 day. A total of 325 patients were entered, stratified into groups with anterior (37%) or inferior or other (63%) acute myocardial infarction, randomized to receive APSAC or rt-PA and followed up for 1 month. RESULTS At entry, patient characteristics in the two groups were balanced. Convalescent ejection fraction at the predischarge study averaged 51.3% in the APSAC group and 54.2% in the rt-PA group (p less than 0.05); at 1 month, ejection fraction averaged 50.2% versus 54.8%, respectively (p less than 0.01). In contrast, ejection fraction showed similar augmentation with exercise at 1 month after APSAC (+4.3% points) and rt-PA (+4.6% points), and exercise times were comparable. Coronary artery patency at 1 day was high and similar in both groups (APSAC 89%, rt-PA 86%). Mortality (APSAC 6.2%, rt-PA 7.9%) and the incidence of other serious clinical events, including stroke, ventricular tachycardia, ventricular fibrillation, heart failure within 1 month, recurrent ischemia and reinfarction were comparable in the two groups; and mechanical interventions were applied with equal frequency. A combined clinical morbidity index was determined and showed a comparable overall outcome for the two treatments. CONCLUSIONS Convalescent rest ejection fraction was high after both therapies but higher after rt-PA; other clinical outcomes, including exercise function, morbidity index, and 1-day coronary artery patency, were favorable and comparable after APSAC and rt-PA.

Effects of Early Thrombolytic Therapy (Anistreplase Versus Streptokinase) on Enzymatic and Electrocardiographic Infarct Size in Acute Myocardial Infarction

The effects of thrombolytic therapy on enzymatic and electrocardiographic indexes of myocardial infarction were examined in 370 patients who were enrolled within 4 hours of onset of symptoms and were randomized to blinded therapy with intravenous anistreplase (30 U/5 min, n = 188) or streptokinase (1.5 million IU/1 hour, n = 182). Creatine kinase and its MB isoenzyme were initially measured every 4 to 6 hours, and lactic dehydrogenase (LDH) and its cardiac isoenzyme (LDH-1) every 8 to 12 hours. Electrocardiograms were obtained before, and at 90 minutes and 8 hours after starting thrombolysis, and on discharge. Enzymatic and electrocardiographic measures of infarction were compared between drug treatment and patency groups. Early patency was associated with significant reductions in peak values for each of 4 cardiac enzymes (averaging 21 to 25%, p less than 0.01 to 0.001), even though later rescue procedures were often used in the nonpatient group; times to peaks were also reduced for 3 of the enzymes. Treatment with anistreplase was associated with enzymatic peaks that tended to be lower than with streptokinase (6 to 16%), approaching or reaching significance for LDH (p less than or equal to 0.07) and LDH-1 (p less than or equal to 0.04); times to peaks were similar. Early patency favorably affected electrocardiographic indexes. Summed ST-segment elevations resolved more rapidly (p less than or equal to 0.04), summed Q-wave amplitude was reduced by 32% (p less than or equal to 0.01), and total QRS infarct score on discharge was 22% less (p less than or equal to 0.006) in those achieving early patency. Small differences in electrocardiographic indexes between the 2 drug treatment groups were not significant. These results support use of early reperfusion to reduce infarct size in acute myocardial infarction with administration of streptokinase and anistreplase.

Relation of reperfusion success with anistreplase or alteplase in acute myocardial infarction to body weight

Adjustment in dose based on body size is not recommended currently for thrombolytic regimens, except for a reduction in alteplase (recombinant tissue-type plasminogen activator [rt-PA]) dose for safety reasons in patients with low body weight. It is unresolved how to dose thrombolytic agents in very heavy patients. The study objective was to assess whether patency of the infarct-related artery at 1 day after therapy with anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) or rt-PA is adversely affected by increased body weight. Data were analyzed from a double-blind, randomized, comparative study of APSAC (30 U/5 min) versus rt-PA (100 mg/3 hours, adjusted downward for body weight < 65 kg), together with heparin and aspirin, in patients with acute myocardial infarction presenting within 4 hours of symptom onset. Coronary patency, determined at 1 day, was assessed in a blinded fashion, and patency success was correlated with body weight, divided into quintiles. In patients treated with APSAC, coronary patency rates were similar in those in the upper quintile of body weight (> 94 kg; n = 22) and in the low-normal weight group (n = 126) (86 and 90%, respectively, for perfusion grade 2/3 [p = 0.64]; and 82 and 74%, respectively, for grade 3 [p = 0.42]). In contrast, for the rt-PA group, heavy patients (n = 34) achieved significantly lower patency rates (74 vs 89% for grade 2/3 [p = 0.02]; and 59 vs 77% for grade 3 [p = 0.03]). The dose of heparin administered, adjusted to maintain a therapeutic partial thromboplastin time until the 1-day (mean 28 hours) angiogram, was greater in the heavy than in the low-normal weight group (mean +/- SE 39,680 +/- 4,818 vs 30,027 +/- 1,177 U; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Signal-Averaging Electrocardiographic Systems Using Device Specific Criteria in 104 Normal Subjects

The advent of several signal‐averaged electrocardiogram (SAECG) systems for late potential (LP) assessment warrants comparisons to assess intersystem reproducibility and variability. Simultaneous SAECGs on two systems. Arrhythmia Research Technology (ART) and Marquette (MEI), were performed on 104 normal volunteers (53 males, age 44 ± 14 years), and analyzed filtered QRS duration (TEQRS), root mean square voltage (RMS40), and low amplitude signal duration (LAS40), filtered at 40–250 Hz. The Gomes criteria (TFQRS > 114 msec, RMS40 < 20 μV and LAS40 > 38 msec) were used as criteria for LP. The data was also analyzed using the recently proposed system specific criteria for MEI (TFQRS >120 msec, RMS40 <20 μV and LAS40 > 38 msec). Where appropriate, statistical analysis was performed using simple linear and Spearmans rank correlation, analysis of variance, Finns R and cNemars test. Results: The means ± SD for ART and MEI were: TFQRS: 97.2 ± 8.9 vs 108.2 ± 7.2 msec (R = 0.76), RMS40: 31.8 ± 17.8 vs 45.3 ± 19.9 μV (R = 0.53), and LAS40: 32.2 ± 8.4 vs 30 ± 7.4 (R = 0.54). When the Gomes criteria were applied, the number of subjects identified by each system as abnormal were: TFQRS = 3 vs 22 (P < 0.001), RMS 40 > = 20 vs 8 (P = 0.004), LAS40 = 21 vs 9 (P = 0.004), TFQRS/RMS40 = 3 vs 6 (P = 0.38), TFQRS/LAS40 = 3 vs 7 (P = 0.22), RMS40/LAS40 40 = 17 vs 8 (P = 0.02), and all three criteria = 3 vs 6 (P = 0.38) for ART vs MEI, respectively. Percent agreement was 81.7% for TFQRS and 84.6% for RMS40 and LAS40 when single criteria were applied. Agreement improved when combined criteria were utilized (87.5%–95.2% for any two criteria and 95.2% for all three criteria). The intersystem agreement that was not due to chance was 0.63–0.69 for single criteria and 0.75–0.90 for combined criteria. Disagreement was highly significant for the three criteria when used singly and for RMS40 and LAS40 combined. Disagreement was not significant when TFQRS was used in combination with ≥ one other criteria. When the MEI criteria were applied, there was a decrease in the number of subjects identified by the MEI system as abnormal, using the TFQRS criteria singly or in combination. Percent agreement for system specific TFQRS measurements was 94.2% for single criteria and 97.1% for combined criteria. The intersystem agreement that was not due to chance improved (88–0.94). Disagreement between system specific criteria for TFQRS was not significant (P > 0.05). Conclusion: Our data indicate that although there is a general correlation between ART and MEI measurements, variability is substantial, leading to significant differences when the criteria for LP are applied, especially for single parameter determinations. Thus, there is a need to establish system specific normal ranges and more accurate criteria for LP parameters.