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Biomedical subjects

M D Cerqueira

Publications and source records attributed to M D Cerqueira.

At least 37 records · Page 2Linked to original sources

Appearance of abnormal Q waves early in the course of acute myocardial infarction: implications for efficacy of thrombolytic therapy.

OBJECTIVES: The purpose of this study was to determine the time course of the appearance of abnormal Q waves on the electrocardiogram (ECG) over the first 6 h of symptoms of myocardial infarction and to determine what implications, if any, such Q waves have for the efficacy of thrombolytic therapy. BACKGROUND: Severe myocardial ischemia can produce early QRS changes in the absence of infarction. Abnormal Q waves on the baseline ECG may not be an accurate marker of irreversibly injured myocardium. METHODS: Data from 695 patients who had no past history of myocardial infarction and whose admission ECG allowed prediction of myocardial infarct size in the absence of thrombolytic therapy (Aldrich score) were pooled from four prospective trials of thrombolytic therapy. The presence and number of abnormal Q waves on each patient's initial ECG were recorded. Four hundred thirty-six patients had left ventricular infarct size measured using quantitative thallium-201 tomography a mean (+/- SD) of 52 +/- 43 days after admission. RESULTS: Of patients admitted within 1 h of symptoms, 53% had abnormal Q waves on the initial ECG. Both predicted and final infarct size were larger in patients with abnormal Q waves on the initial ECG independent of the duration of symptoms before therapy (p < 0.001). Despite this finding, the presence of abnormal Q waves on the admission ECG did not eliminate the effect of thrombolytic therapy on reducing final infarct size (p < 0.0001). CONCLUSIONS: Abnormal Q waves are a common finding early in the course of acute myocardial infarction. However, there is no evidence that abnormal Q waves are associated with less benefit in terms of reduction of infarct size after thrombolytic therapy.

Electrocardiography↗

New agents and new techniques in nuclear cardiology.

With the availability of new 99mTc perfusion tracers, nuclear cardiology imaging techniques can provide information on myocardial blood flow and left ventricular function from a single imaging session. Ejection fraction, regional wall motion, and changes in wall thickness can be measured and specificity can be improved by gating the images, without increasing the acquisition time. Similarly, the ability to use conventional gamma cameras to image important positron-emission tomography radiotracers, such as fluorodeoxyglucose, allow cost-effective and widespread applications of positron-emission tomography technology. Thus, new radiotracers and imaging techniques in nuclear cardiology provide incremental and cost-effective diagnostic information in the assessment of coronary artery disease.

Cardiac Output↗

Enhanced bone metabolism induced by acupuncture.

A 29-yr-old man with several years of back pain was referred for a bone scan. High-resolution regional spot images of the skeleton were obtained following intravenous injection of 20 mCi 99mTc-methylene diphosphonate. Posterior and lateral images of the skull showed focal increased uptake in several regions of the skull. Upon questioning, the patient stated that he had received acupuncture treatment for his back pain several times in the same regions as the increased uptake. The needle placement was confirmed by the patient's acupuncturist. Acupuncture can cause enhanced bone metabolism demonstrated by increased activity on bone scans.

Acupuncture Therapy↗

Evaluation of annexin V as a platelet-directed thrombus targeting agent.

Annexin V is a human phospholipid binding protein (M(r) 36,000) that binds with high affinity to activated platelets in vitro. We studied the biodistribution and thrombus binding of annexin V in rabbit and swine models of fully occlusive arterial thrombi formed 1-2 h prior to injection of annexin V. Iodinated annexin V was cleared from blood in a rapid early phase (t1/2 = 6.4 min, 76% of radioactivity) and a slower late phase (t1/2 = 71 min, 24% of radioactivity). Organ uptake was highest in the kidney and spleen and lowest in heart and skeletal muscle. Thrombus/blood uptake ratios were (mean +/- SEM): 6.39 +/- 1.80 for rabbit iliac artery, 6.97 +/- 1.45 for swine carotid artery, and 7.68 +/- 1.70 for swine femoral artery (all p values < 0.01 versus control artery); a control protein, ovalbumin, showed an uptake ratio of 0.59 +/- 0.08 in swine femoral artery thrombi. These results indicate that annexin V is useful as an agent for selective targeting of platelet-containing thrombi.

Animals↗

Serum caffeine levels after 24 hours of caffeine abstention: observations on clinical patients undergoing myocardial perfusion imaging with dipyridamole or adenosine.

Although caffeine attenuates the vasodilatation produced by dipyridamole and adenosine, and is therefore contraindicated when these agents are used for myocardial perfusion scintigraphy, caffeine levels in clinical patients undergoing standard imaging protocols have not been studied. Eight-six patients undergoing clinically indicated intravenous dipyridamole (n = 75) or adenosine (n = 11) thallium-201 myocardial perfusion scintigraphy, all of whom reported abstention from products containing caffeine for 24 h, were studied prospectively. Blood samples were drawn prior to initiation of the pharmacologic infusion, and serum caffeine levels were determined using an enzyme immunoassay technique. Results of these determinations were correlated with maximum pulse and blood pressure changes measured during and immediately after the stressor infusion, and thallium imaging findings. Detectable caffeine levels were found in 34 patients (40%), ranging from 0.1 to 5.0 mg/l. There was no significant difference in mean systolic blood pressure decrease or mean pulse increase between patients with caffeine levels > 1.0 mg/l (20.4 +/- 18.2 mmHg, 11.0 +/- 8.9 BPM; n = 5) and those with lower (0.1 to 0.9 mg/l) (15.4 +/- 9.5 mmHg, 14.4 +/- 8.2 BPM; n = 29) or no detectable caffeine levels (18.0 +/- 11.5 mmHg, 16.6 +/- 10.1 BPM; n = 52). Redistribution on thallium imaging was also identified with a similar frequency in these three groups (2/5, 40%; 8/29, 28%; 22/52, 42% respectively).

Adenosine↗

Safety profile of adenosine stress perfusion imaging: results from the Adenoscan Multicenter Trial Registry.

OBJECTIVES: The purpose of this study was to determine the safety of adenosine infusion at 140 micrograms/kg per min in conjunction with radionuclide imaging in 9,256 consecutive patients. BACKGROUND: Adenosine produces maximal myocardial hyperemia directly with a rapid onset of action. In addition, when used in conjunction with radionuclide perfusion imaging, it has proven efficacy for the diagnosis of coronary artery disease in patients unable to exercise. Because the ultrashort half-life (< 10s) allows dose titration and rapid reversal of side effects, it may be safer than other available pharmacologic agents. METHODS: Patients were prospectively entered at 21 clinical sites. Information on safety and adverse events during and immediately after adenosine infusion was maintained in the Adenoscan Multicenter Trial Registry. RESULTS: The infusion protocol was completed in 80% of patients, required dose reduction in 13% and was terminated early in 7%. Interpretable imaging studies were obtained in 98.7% of patients, and 0.8% of patients received aminophylline. Minor and well tolerated side effects were reported in 81.1% of patients. There were no deaths, one myocardial infarction, seven episodes of severe bronchospasm and one episode of pulmonary edema. Transient atrioventricular (AV) node block occurred in 706 patients (first-degree in 256, second-degree in 378 and third-degree in 72) and resolved spontaneously in most patients (n = 508) without alteration in the adenosine infusion. There were no sustained episodes of AV block. Patients > 70 years of age had an increased risk of developing AV block (age < 70, 7.05% vs. > or = 70, 9.44%, p = 0.001, relative risk 1.37). CONCLUSIONS: Adenosine infusion is safe. Vasodilator and negative dromotropic side effects are generally well tolerated. Serious side effects are relatively rare, and they reverse with termination of adenosine infusion. Interpretable radionuclide studies were obtained in 98.7% of patients and aminophylline reversal was seldom required.

Adenosine↗

Beta-adrenergic effects on left ventricular filling: influence of aging and exercise training.

Reduced heart rate and contractile responses to beta-agonist stimulation characterize normal cardiac aging, but whether diastolic responses also decline with aging has not been determined in humans. Diastolic filling responses to isoproterenol were determined in 13 older (60-82 yr) and 11 young (24-32 yr) healthy men before and after endurance training. Filling rates were expressed in three ways: 1) normalized to end-diastolic volume per second, 2) normalized to stroke volume per second, and 3) as absolute milliliters of blood (ml.s-1.m-2). Peak early filling rates by all methods were reduced at rest and all isoproterenol doses with aging (all P < 0.0001 for old vs. young), whereas peak atrial filling rates were increased with aging. During isoproterenol, both peak early and peak atrial filling rates increased significantly (all P < 0.01); the increase in filling rates with isoproterenol was not different with aging (all NS for old vs. young x dose). Endurance training did not augment diastolic filling responses to isoproterenol. Although diastolic filling rates at rest are markedly altered by aging, diastolic filling responses to isoproterenol are not reduced with aging. Thus the age-associated declines in heart rate, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol do not extend to diastolic filling responses.

Adolescent↗

Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men.

BACKGROUND: Cardiac aging alters many of the acute responses to exercise stress, but the extent to which chronic exercise (ie, training) can alter or improve the effects of aging in humans is largely unknown. METHODS AND RESULTS: Cardiovascular responses to graded supine exercise stress (beginning at 200 kpm and increasing by 200 kpm every 3 minutes till exhaustion) were assessed using radionuclide ventriculography in 13 older (age, 60 to 82 years) and 11 young (age, 24 to 32 years) rigorously screened healthy men before and after 6 months of endurance training. Repeated-measures ANOVA was used to test significance. During exercise, the old group had a lesser increase in heart rate (+105% old versus +166% young), a greater increase in mean blood pressure (+35% old versus +22% young), lesser increases in ejection fraction (+3 ejection fraction units old versus +11 units young) and peak ejection rate (+62% old versus +119% young), a greater increase in end-diastolic volume index (+8% old versus -10% young), a lesser fall in end-systolic volume index (-0% old versus -32% young), and a lesser increase in cardiac index (+135% old versus +189% young) (all P < .01 young/old versus exercise stage). Stroke volume index response to exercise was not different with aging (+14% old versus +6% young, P = NS). Exercise training increased maximal oxygen intake by 21% in the older group (28.9 +/- 4.6 to 35.1 +/- 3.8 mL.kg-1.min-1, P < .001) and by 17% in the young (44.5 +/- 5.1 to 52.1 +/- 6.3 mL.kg-1.min-1, P < .001) and increased peak workload by 24% in the old and 28% in the young. Exercise training had no differential effects on old versus young men. Among all subjects, training significantly reduced the resting heart rate by 12% (-8 beats per minute) and increased resting end-diastolic volume index by 13% (+9 mL/M2) and resting stroke volume index by 18% (+7 mL/M2) (all P < .01). At peak exercise, cardiac index increased by 16% (+1.07 L.M-2.min-1) compared with before training, which was the result of an increase in stroke volume of 18% (+7 mL/M2) (P < .001); peak heart rate was unchanged. The increase in stroke volume index at peak exercise was the result of both a 12% increase in end-diastolic volume index (+8 mL/M2) (P < .01) and an increase in ejection fraction (+3 ejection fraction units) (P < .05) at peak exercise. The increased ejection fraction at peak exercise occurred despite a 9% increase in systolic blood pressure (+18 mm Hg) (P < .01), suggesting an increase in contractility. Thus, both the young and old increased peak exercise cardiac output by use of the Frank-Starling mechanism (ie, cardiac dilatation) as well as an increase in ejection fraction. CONCLUSIONS: We conclude that there is an age-associated decline in heart rate, ejection fraction, and cardiac output responses to supine exercise in healthy men. Although the stroke volume responses of the young and old are similar, the old tend to augment stroke volume during exercise more through cardiac dilatation, with an increase in end-diastolic volume (+8%) but without much change in ejection fraction (+3 ejection fraction units), whereas the young rely more on an increase in the ejection fraction (+11 ejection fraction units) with no cardiac dilatation (-10%). Despite the significant cardiovascular changes that occur in the response to a single bout of exercise with aging, adaptations to chronic exercise training were not different with aging and included improvements in maximal workload and increases in ejection fraction, stroke volume index, and cardiac index at peak exercise.

Adult↗

Imaging arterial thrombosis: comparison of technetium-99m-labeled monoclonal antifibrin antibodies and indium-111-platelets.

UNLABELLED: Imaging with the 99mTc-T2G1s monoclonal antifibrin antibody fragment (Fab') has demonstrated promise in the noninvasive detection of venous thrombi in humans. The purpose of this study was to determine whether chronic arterial thrombi can also be detected by antifibrin antibody imaging. METHODS: Eighteen subjects with chronic arterial thrombi were studied with planar and tomographic imaging at 0 to 24 hr postinjection of 99mTc-labeled T2G1s monoclonal antifibrin antibody fragment. Imaging with 111In-labeled platelets was also performed. Images were visually graded by two observers as 0, 1, 2 or 3 (no, faint, moderate or marked) uptake, and quantitative analysis of tomographic images was done in 13 subjects. RESULTS: On visual analysis of planar images, 44% (8 of 18) of antifibrin patient studies were 1.0 or more and 66% (10 of 18) were judged negative compared with 94% (15 of 16) of platelet patient studies judged 1.0 or more and 6% (1 of 16) judged as negative (p < 0.01). Visual analysis of tomographic images was similar, with 61% (11 of 18) of antifibrin studies graded 1.0 or more compared with 100% (17 of 17) of platelet studies (p < 0.01). The tomographic target-to-background ratio was higher with platelets than with antifibrin antibody (2.5 +/- 1.4 versus 1.8 +/- 1.0, p < 0.05). CONCLUSION: In the large-vessel chronic arterial thrombi studied, the results of 99mTc-labeled monoclonal T2G1s antifibrin Fab' imaging were positive in only one-half of the patients studied, significantly less than the findings with platelet imaging, which were positive in all subjects. The higher rate of positive images with labeled platelets than with labeled antifibrin antibodies may be largely due to thrombus age, with continued platelet deposition but little active fibrin deposition.

Aged↗

Endurance exercise training augments diastolic filling at rest and during exercise in healthy young and older men.

BACKGROUND: Diastolic filling at rest is altered markedly with advancing age. Whether exercise training can improve diastolic filling at rest or during exercise in either healthy older or healthy young men has not been determined. The purpose of this study was to determine if 6 months of aerobic exercise training improves diastolic filling. METHODS AND RESULTS: Radionuclide diastolic filling parameters were measured at rest and during exercise in 14 older (age, 60 to 82 years) and 17 young (age, 24 to 32 years) rigorously screened healthy males before exercise training and in 13 older and 11 young men after 6 months of endurance exercise training. Diastolic filling rates were expressed in two ways, as absolute milliliters of blood (mL.s-1.m-2) and normalized to the end-diastolic volume. At baseline, the peak early filling rates were lower in the older group compared with the young group as expressed in absolute milliliters of blood (older, 85 +/- 7 mL.s-1.m-2; young, 173 +/- 10 mL.s-1.m-2; P < or = .0001) and in end-diastolic volume per second (1.66 +/- 0.11 versus 2.55 +/- 0.08, P < .0001), whereas the peak atrial filling rates were greater in absolute milliliters of blood (85 +/- 5 versus 56 +/- 7 mL.s-1.m-2, P = .003) and in end-diastolic volume per second (1.70 +/- 0.12 versus 0.80 +/- 0.06, P < .0001). During exercise, at any given heart rate, the older group had a lower peak filling rate than the young group. Also, at peak exercise, the single peak filling rate was decreased in the older group in mL.s-1.m-2 (384 +/- 19 versus 565 +/- 36 mL.s-1.m-2, P = .0002) and in end-diastolic volume per second (6.01 +/- 0.25 versus 7.91 +/- 0.28 end-diastolic volume per second, P < .0001). Six months of intensive aerobic exercise training had similar effects in the old and young groups overall. Maximal oxygen consumption increased 19% (ANOVA training effect, P < or = .0001) and echocardiographic left ventricular mass increased 8% (ANOVA training effect, P = .002). Training increased the resting peak early filling rate in absolute milliliters of blood by +14% (ANOVA training effect, P = .02). During exercise, the peak early or single peak filling rate at any given heart rate was increased. At peak exercise, the single peak filling rate was increased by 14% in mL.s-1.m-2 (ANOVA training effect, P = .0004). The only age-related differential effect of training was on the peak atrial filling rate in end-diastolic volume per second, which decreased by 27% in the older group but was unchanged in the young (+5%) (ANOVA young versus older, P = .001). The independent predictors of a greater maximal oxygen consumption by multivariate analysis were a higher peak exercise heart rate, a greater resting peak early filling rate, the exercise trained state, and a younger age. CONCLUSIONS: Healthy older men have reduced early diastolic filling at rest and during exercise compared with young men. Endurance exercise training enhances early diastolic filling at rest and during exercise in both the old and the young. Training reduces the elevated resting atrial filling rate in the old, whereas the young were unchanged. The training-induced augmentation of early diastolic filling at rest and during exercise may be an important adaptation to allow an increase in stroke volume at rest and an increase in stroke volume, cardiac output, and maximal oxygen consumption during exercise.

Adult↗

Evaluation of pulmonary systemic blood flow using ECG gated acquisition.

We propose a functional parametric analysis method using ECG-gated 99mTc-labeled red blood cell (RBC) imaging for detection and characterization of periodic variations in local blood activity in the lungs during cardiac cycle. We validated in animal experiments that such count variations correlate with cyclical pulmonary blood flow and may be used for evaluation of systemic-to-pulmonary shunts. Clinical studies were performed in 48 patients. After labeling the RBC pool with 99mTc, ECG-gated gamma camera images of both lung fields were acquired and processed to obtain Fourier transforms of time/activity functions in selected regions. The first harmonic parametric images of amplitude and phase were derived. There was an excellent correlation (r = 0.92) between activity variations and pulsatile flow measured by our method with that obtained by the thermodilution method in dog experiments (n = 10) after implantation of a systemic-to-pulmonary shunt. Patient studies showed the technique to be sensitive in detecting and quantifying abnormal systemic-to-pulmonary blood flow. Lung pulsatile flow can thus be noninvasively measured from functional parametric phase and amplitude images; the technique may be useful for detecting and quantifying abnormal systemic-to-pulmonary blood flow in man.

Animals↗

Photopenic defects in marrow-containing skeleton on indium-111 leucocyte scintigraphy: prevalence at sites suspected of osteomyelitis and as an incidental finding.

The skeletal distribution of red marrow-containing sites with a decreased uptake of indium-111-labelled leucocytes was examined as part of a retrospective review of 128 consecutive scans in 113 patients. The prevalence of photopenic defects was determined for sites of suspected osteomyelitis and for other skeletal locations included as part of limited or total-body surveys. Of 52 sites suspected of osteomyelitis based upon radiological and clinical data, 21 (40%) demonstrated a decreased leucocyte uptake. The prevalence of photopenia ranged from 79% (11/14) in the spine and 63% (5/8) in the pelvis to 25% (4/16) in the proximal femur and 0% elsewhere in the extremities (0/9) and in the skull (0/3). Fourteen of these 21 defects (67%) were due to active (n = 9) or healed (n = 5) osteomyelitis/discitis. All sites of active osteomyelitis showed destructive changes on correlative radiographs and were associated with infectious processes of more than 1 months duration. Thirty-seven photopenic defects were observed as incidental findings. The prevalence of photopenia as an incidental finding ranged from 0% in the skull, neck and chest to 3%-4% in the thoracolumbar spine and pelvis and 14% in the femoral heads, the latter reflecting primarily bilateral loss of femoral head marrow. No incidentally found photopenic defect reflected active osteomyelitis. At sites in the spine and pelvis with radiologic evidence of bone destruction suggestive of osteomyelitis, an absence of normal red marrow uptake of labelled leucocytes often reflects a variant presentation for active chronic infection. In contrast, incidental photopenia is uncommon at all skeletal sites except the femoral heads, and should not raise concern over unsuspected active osteomyelitis.

Bone Marrow↗

Effect of intensive endurance training on lipoprotein profiles in young and older men.

Although there are considerable data concerning the effects of endurance exercise training (ET) on plasma lipoproteins, the results have been quite inconsistent. The observed variability of response may be related to the age, sex, adiposity, or diet of the subjects tested, or to the type and intensity of the exercise intervention. Furthermore, there is relatively little such data in older individuals. Therefore, in the present study, we investigated the effects of intensive ET on lipoprotein profiles in healthy young (n = 12; 28.2 +/- 2.4 years) and older (n = 15; 67.5 +/- 5.8 years) men. Unlike subjects in most similar studies, our subjects were weight-stabilized on a constant-composition diet for 21 days prior to determination of the lipoprotein profile before and after the ET program. At baseline, the two groups were not significantly different with respect to any individual component of their lipoprotein profiles, relative weight, or percent body fat, but the older men had a more central distribution of fat by both waist to hip ratio (WHR) and computed tomography (CT). Maximal aerobic power, expressed per kilogram of body weight (VO2 max), was 33% lower (P less than .001) in the older men at baseline. Following the 6-month, walk/jog/bike ET program (5 d/wk), both the young (+18%, P less than .001) and the older (+22%, P less than .001) men increased their VO2 max. This was associated with small, but significant, decrements in weight, percent body fat, and WHR only in the older men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Quantitative gated blood pool tomographic assessment of regional ejection fraction: definition of normal limits.

OBJECTIVE: Our aim was to select a method of analysis for gated blood pool tomography that reduced variability in a group of normal subjects, allowed comparison with normal limit files and displayed results in the bull's-eye format. BACKGROUND: Abnormalities in left ventricular function may not be accurately detected by measures of global function because hyperkinesia in normal regions may compensate for abnormal regional function. Gated blood pool tomography acquires three-dimensional data and offers advantages over other noninvasive modalities for quantitative assessment of global and regional function. METHODS: Alternative methods for selecting the ventricular axis, calculating regional ejection fraction and choosing the number of ventricular divisions were studied in 15 normal volunteers to select the combination of parameters that produced the lowest variability in quantitative regional ejection fraction. Methods for quantitative comparison of regional ejection fraction with normal limit files and for display in the bull's-eye format were also examined. RESULTS: A fixed axis (the geometric center of the ventricle defined for end-diastole and used for end-systole) gave ejection fractions that were significantly higher in the lateral wall versus in the septum, 82 +/- 8 (mean +/- 1 SD) versus 39 +/- 17 (p less than 0.001) at the midcavity and 66 +/- 11 versus 21 +/- 20 (p less than 0.001) at the base. A floating axis system (axis defined individually for end-diastole and end-systole and realigned at the center) gave more uniform regional ejection fraction: 63 +/- 6 versus 64 +/- 8 (p = NS) at the midcavity and 44 +/- 16 versus 45 +/- 15 (p = NS) at the base. The coefficient of variability for regional ejection fraction was consistently lower using a floating axis. Calculating regional ejection fraction by dividing the regional stroke volume by the end-diastolic volume of the region gave a lower coefficient of variability and a more easily understood value than dividing the regional stroke volume by the total end-diastolic volume of the ventricle. Although the variability was lower using five versus nine ventricular divisions, nine regions offer greater spatial resolution. Comparison of regional ejection fraction with normal data identified regions greater than 2.5 SD below the mean as abnormal. We described the two-dimensional bull's-eye format as a method for displaying the regional three-dimensional data and illustrated abnormalities in patients with prior myocardial infarction. CONCLUSIONS: Gated blood pool tomography performed using a floating axis system, regional stroke volume calculation of ejection fraction and nine regions uses all the three-dimensional blood pool data to calculate regional ejection fraction, allow quantitative comparison with normal limit files, display the functional data in the two-dimensional bull's-eye format and demonstrate abnormalities in patients with myocardial infarction.

Adult↗

Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials.

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

Aged↗