Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease

Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of^99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of^99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. This phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion,^99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.     

Investigation of pulmonary epithelial permeability in patients after hyperbaric oxygen therapy by 99mTc diethylenetriaminepentaacetic acid aerosol inhalation lung scintigraphy

The aim of this study was to evaluate the possibility of pulmonary epithelial permeability damage in patients after hyperbaric oxygen therapy (HBOT) by 99mTc diethylenetriaminepentaacetic acid (99mTc-DTPA) aerosol inhalation lung scintigraphy. Twenty-five controls and 21 patients with normal chest X-rays and no cigarette smoking for at least 1 year were recruited for the study. 99mTc-DTPA aerosol inhalation lung scans were performed after 20 HBOT sessions in 21 patients with refractory osteomyelitis or diabetic foot. The HBOT with 100% oxygen at 2.5 atm absolute for 100 min was performed five times a week. Clearance rates (%/min) of 99mTc-DTPA aerosol in each lung field were calculated from the dynamic images for 30 min. Clearance rates of 99mTc-DTPA aerosol were compared between patients and controls by the unpaired t test. Thirteen patients who had 99mTc-DTPA aerosol lung scans before and after HBOT therapy studies were tested for statistical significance by using the paired t test. There was no statistically significant difference (P>0.05, unpaired t test) between patients and controls in every lung field. For the 13 patients who had 99mTc-DTPA aerosol studies both before and after 20 HBOT sessions, the results also showed no statistically significant difference (P>0.05, paired t test). It is concluded that there was no demonstrable pulmonary epithelial permeability change under current clinical HBOT protocol.     

Predictive value of (99m)Tc sestamibi scintigraphy in the evaluation of doxorubicin based chemotherapy response in patients with advanced breast cancer

Resistance to doxorubicin based chemotherapy is a major therapeutic problem limiting advanced breast cancer treatment. 99mTc hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been reported to be extruded from tumour cells by the P-glycoprotein and multidrug resistance protein encoded by MDR1 and MRP1 genes, respectively. These proteins are involved in the cellular efflux of several chemotherapeutic agents including doxorubicin. The aim of this study was to investigate the clinical value of a standard (99m)Tc-MIBI scintimammography technique in the prediction of response to chemotherapy in advanced breast cancer patients. Fifty-six lesions from 33 female patients with locally advanced (n=27) or recurrent breast cancer (n=6) were included in the study. MIBI scintigraphy was performed 2-8 days prior to chemotherapy (FAC regimen). Images were acquired 10 min and 1 h post-injection of 740-1110 MBq of (99m)Tc-MIBI. Tumour-to-normal background tissue uptake ratios were calculated on each lesion in the early (T/B(e)) and delayed phase of the study (T/B(d)). Both T/B(e) and T/B(d) ratios were significantly higher (P<0.0001) in responders (n=43) than nonresponders (n=13). Diagnostic values of (99m)Tc-MIBI in the prediction of chemotherapy response were evaluated using the arbitrary cut-off values of 1.5 for T/B(e) and 1.4 forT/B(d). Sensitivity, specificity, positive and negative predictive values were 88.4%, 92.3%, 97.4%, 70.6%; and 90.7%, 100.0%, 100.0%, 76.6%, for T/B(e) and T/B(d), respectively. We conclude that (99m)Tc-MIBI scintigraphy may be a clinically valuable tool for guiding chemotherapy in advanced breast cancer patients.     

Increasing the radiochemical purity of 99mTc sestamibi commercial preparations results in improved sensitivity of dual-phase planar parathyroid scintigraphy

BACKGROUND: Poor results for dual-phase parathyroid scintigraphy have recently prompted increased use of dual-tracer imaging. We noticed that seminal studies used higher radiochemical purity than provided by current commercial preparations meeting US Pharmacopea (USP) specifications (90% of technetium bound to sestamibi). We surmised that the presence of unbound Tc (non-MIBI tracer) might hamper dual-phase detection that is dependent on rapid wash-out of technetium from thyroid tissue. PURPOSE: To test the hypothesis that reducing non-MIBI tracer will enhance thyroid wash-out and improve sensitivity of dual-phase imaging. METHODS: Starting in April 2003 we decreased the technetium to sestamibi ratio. This resulted in a significant decrease of non-MIBI tracer from 8.1+/-2.2% (SD) (group 1, n = 42) to 3.5+/-1.1% (group 2, n = 47) (P < 0.05 t-test). We performed a retrospective review of 89 patients with primary hyperparathyroidism who underwent imaging and subsequent surgery. The pathological findings served as the 'gold standard'. RESULTS: Scanning detected 21/39 diseased glands (sensitivity=54%) in group 1 patients. In group 2 imaging detected 38/45 diseased glands (sensitivity = 84%). An improvement in sensitivity (P < 0.01) was achieved by modifying the radiopharmaceutical preparation. CONCLUSIONS: Elevated levels of non-MIBI tracer in Tc-MIBI commercial preparations result in persistent thyroid background activity that may interfere with detection of parathyroid pathology. Achieving a higher degree of radiochemical purity (at least 95% bound, 5% impurities) than required by USP may be needed for optimal results. The large variation in sensitivity reported in the literature may be related in part to non-uniform radiopharmaceutical preparation.     

The usefulness of 99mTc tetrofosmin scintigraphy in patients with breast cancer recurrences

To verify the usefulness of 99mTc tetrofosmin scintigraphy in the follow-up of breast cancer patients, we studied 72 surgically treated breast cancer patients with suspected local recurrences (20 cases) or distant metastases (52 cases) at clinical examination and/or at conventional imaging procedures (CIPs). In all patients, a whole-body scan followed by planar and single photon emission tomography (SPET) images of selected sites were acquired 10 min after the intravenous injection of 740 MBq of 99mTc tetrofosmin, using a rectangular dual-head gamma camera equipped with high-resolution parallel-hole collimators. Loco-regional recurrences were diagnosed in 19 patients and distant metastases in 44 cases, while benign lesions were ascertained in nine cases. 99mTc tetrofosmin SPET showed higher sensitivity, specificity and accuracy per patient than did CIP (96.8% vs 85%, 77.7% vs 55.5% and 94.4% vs 81.1%, respectively) with statistical significance for accuracy (P <0.05). The combined use of SPET and CIP achieved 100% sensitivity and 98.6% accuracy. Planar imaging did not give additional information in respect of either SPET or CIP, showing significantly lower sensitivity and accuracy values (47.6% and 52.8%, respectively). Our data seem to suggest that 99mTc tetrofosmin SPET, but not planar, may be useful in the follow-up for the detection of loco-regional and distant recurrences in patients with breast cancer. The technique can play a complementary role to conventional diagnostic imaging procedures in selected patients.     

99mTc depreotide scan compared with 99mTc-MDP bone scintigraphy for the detection of bone metastases and prediction of response to hormonal treatment in patients with breast cancer

BACKGROUND: The purpose of this study was to determine the potential role of Tc depreotide scintigraphy for the evaluation of bone metastases compared with Tc methylenediphosphonate (MDP) bone scintigraphy and for the prediction of treatment response in breast cancer patients in whom first- or second-line hormonal therapy was to be initiated. METHODS: Twelve patients with a diagnosis of advanced breast cancer were included. All patients underwent both a bone scan and a depreotide scan and at least one other conventional imaging procedure, including plain film radiography (n=11), computed tomography (n=6) or magnetic resonance imaging (n=5), for confirmation of metastatic disease. The mean time interval between the bone scan and the depreotide scan was 30.6 days. Follow-up data were retrieved from routine clinical evaluation by means of physical examination, imaging and blood analysis. RESULTS: On a patient basis we found a sensitivity, specificity and accuracy of, respectively 100%, 50% and 83.3% for the bone scan and 62.5%, 100% and 75% for the depreotide scan in the diagnosis of bone metastasis. In eight patients with available follow-up data two with a positive depreotide scan remained stable and five of six patients with a negative depreotide scan had progressive disease. CONCLUSION: In this small series of breast cancer patients Tc depreotide scintigraphy proves less sensitive but more specific as compared to Tc-MDP bone scintigraphy in measuring the extent of bone metastasis. On the other hand Tc depreotide scintigraphy elucidates, non-invasively, tumour characteristics and may be indicative for prognosis and response to hormonal treatment.     

Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of recurrent of persistent hyperparathyroidism

PURPOSE: To compare the sensitivity and positive predictive value of magnetic resonance (MR) imaging and technetium 99m 2-methoxyisobutyl-isonitrile (MIBI) scintigraphy for the detection of hyperfunctioning parathyroid tissue when used alone and in combination in a large patient population with recurrent or persistent hyperparathyroidism (HPT). MATERIALS AND METHODS: In 98 consecutive patients with biochemically proved recurrent or persistent HPT after surgery, MR imaging and 99mTc MIBI study findings were retrospectively reviewed and compared with surgical and histopathologic findings. The sensitivity and positive predictive value of MR imaging and 99mTc MIBI scintigraphy were compared with each other and in combination. RESULTS: In these patients, 130 abnormal parathyroid glands were identified at surgery. The sensitivity and positive predictive value of MR imaging were 82% (95% CI: 75%, 89%) and 89%, respectively; those for (99m)Tc MIBI scintigraphy were 85% (95% CI: 79%, 91%) and 89%. No significant difference was found between MR imaging and 99mTc MIBI scintigraphy for sensitivity (P =.7). The sensitivity and positive predictive value for the detection of abnormal parathyroid tissue on a per-gland basis increased to 94% (95% CI: 90%, 98%) and 98%, respectively, when only one of the two tests was required to be positive. CONCLUSION: MR imaging and 99mTc MIBI scintigraphy have similarly good sensitivity and positive predictive value for the detection of hyperfunctioning parathyroid tissue in patients after surgery. The combination of the two tests provided a substantial increase in sensitivity and positive predictive value.     

Use of99mTc-MIBI scintigraphy in the evaluation of the response of osteosarcoma to chemotherapy

The use of gamma camera scintigraphy with technetium-99m hexakis-2-methcxyisobutylisonitrile (^99mTc-MIBI) for assessment of the response of high-grade osteosarcoma to preoperative chemotherapy was evaluated. Twelve patients with osteosarcoma of the extremities underwent planar examination with^99mTc-MIBI before and after preoperative chemotherapy according to the recommendations of the Scandinavian Sarcoma Group. After calculating a quotient for the tumour and the average activity of both extremities and correcting for background activity, the change in uptake between the two examinations was assessed. This was compared with histological examination of the ultimately resected specimen in 11 patients and progressive clinical disease in one. All the 11 tumours undergoing histological examination showed cellular necrosis of between 50% and 100% as well as a reduced uptake of^99mTc-MIBI, while the single progressive tumour showed an increased uptake. There was a correlation between the reduction of radiopharmaceutical uptake and the histological response in the entire series, while the variation was too large to allow conclusions in individual patients. This variation may have biological reasons or may be due to the planar imaging technique, which only allows semi quantitative evaluation. The technique reflects response to therapy but is not yet clinically applicable for the identification of poor responders, which would serve as a basis for alteration of the chemotherapy regimen. In order to evaluate whether such a role could be fulfilled, further studies using single-photon emission tomography with correction for attenuation and scattering of photons are necessary.     

Prediction of response to revascularization in patients with renal artery stenosis by Tc-99m-ethylenedicysteine captopril scintigraphy

The aim of the present study was to assess the predictive value of captopril scintigraphy with the new renal agent 99mTc-ethylenedicysteine (99mTc-EC) for post-interventional improvement in blood pressure. Twelve patients who had persistently high blood pressure with previous demonstration of various degrees of renal artery lesion on angiography were included into the study. Baseline and captopril scintigraphies were performed on the same day at 4 hour intervals after the injection of 74 and 296 MBq of 99mTc-EC, respectively. All patients had percutaneous transluminal angioplasty (PTA), and improvement in blood pressure was evaluated 3-6 months after the intervention. 99mTc-EC captopril scintigraphy successfully predicted a positive or negative outcome in 11 of 12 patients. In one patient with captopril induced renal function deterioration, scintigraphy failed to predict post-interventional response. Our preliminary findings showed that 99mTc-EC captopril scintigraphy can be used to determine patients who will benefit from revascularization.     

Efficiency of gamma probe and dual-phase Tc-99m sestamibi scintigraphy in surgery for patients with primary hyperparathyroidism

PURPOSE: The purpose of this study was to determine the value of the intraoperative gamma probe and the efficacy of dual-phase Tc-99m sestamibi imaging in patients with primary hyperparathyroidism. METHODS: Twenty-one patients with primary hyperparathyroidism were examined prospectively. Results of same-day dual-phase Tc-99m sestamibi scintigraphy and intraoperative gamma probe evaluations were compared with the intraoperative findings and histopathologic diagnoses. A 15-mm handheld gamma probe was used to measure gamma activity in the neck and upper mediastinum. Nuclear mapping by gamma probe showed a single quadrant of neck that emitted gamma radiation significantly greater than the other three quadrants, which correlated with the sestamibi scan. RESULTS: Dual-phase Tc-99m sestamibi scintigraphy determined and localized parathyroid lesions in 20 patients (sensitivity, 94%). Of the 20 parathyroid lesions removed, 15 were located in normal positions, whereas five were explored in ectopic sites (one within the thyroid, one in the anterior mediastinum, one in a retrotracheal position, one in the carotid sheath, and one in the retroesophageal region). Although the index of thyroid nodules varied from 15.8% to 22.9%, the index for parathyroid lesions was 77.3% to 112.8%. CONCLUSIONS: These results confirm that parathyroid lesions, especially at ectopic sites, can be treated successfully in shorter operative times with minimal complications with the help of the intraoperative gamma probe.     

Relationship between evaluation by quantitative fatty acid myocardial scintigraphy and response to beta-blockade therapy in patients with dilated cardiomyopathy.

Predicting the effect of beta-blockade therapy on the clinical outcome of patients with dilated cardiomyopathy (DCM) is difficult prior to the initiation of therapy. Myocardial fatty acid metabolism has been shown to be impaired in patients with DCM. We examined whether the extent of myocardial injury, as assessed by iodine-123 15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy, is related to the response of patients with DCM to beta-blockade therapy. Thirty-seven patients with DCM were examined using BMIPP myocardial scintigraphy before and after 6 months of treatment with metoprolol. Myocardial BMIPP uptake (%BM uptake) was estimated quantitatively as a percentage of the total injected count ratio. The left ventricular end-diastolic and end-systolic dimensions (LVDd, LVDs) and ejection fraction (LVEF) were also evaluated. The patients were divided into two groups according to their functional improvement (>10% elevation of LVEF) after 6 months of metoprolol therapy. Twenty-eight patients responded to the therapy, while nine did not. Prior to the therapy, no significant differences in LVDd, LVDs or LVEF were observed between the responders and non-responders. However, the %BM uptake was significantly lower in the non-responders than in the responders (1.0%+/-0.2% vs 2.1%+/-0.5%, P<0.001). The %BM uptake could be used to distinguish the responders from the non-responders with a sensitivity of 0.93 and a specificity of 1.00 at a threshold value of 1.4. After the metoprolol therapy, the %BM uptake improved significantly in the responders (2.5%+/-0.5%, P<0.01) but did not change in the non-responders. These results indicate that myocardial BMIPP uptake could predict the response of DCM patients to beta-blockade therapy.     

Myocardial perfusion imaging with 99mTc sestamibi early after reperfusion reliably reflects infarct size reduction by ischaemic preconditioning in an experimental porcine model

OBJECTIVE: Reliable methods for assessment of tissue reperfusion early after revascularizing therapy for acute myocardial infarction are needed. Myocardial perfusion imaging with Tc sestamibi (MIBI MPI) may serve this purpose. Usage during early reperfusion may be problematic e.g. due to ischaemic preconditioning (IP), which is important in inducing ischaemic tolerance. It is mediated through the opening of mitochondrial K ATP channels, reducing mitochondrial membrane potential. This may, as well as ischaemia per se, affect cellular uptake of Tc sestamibi. We therefore studied the reliability of MIBI MPI during early reperfusion as a measure of infarct size and its reduction by ischaemic preconditioning. METHODS AND RESULTS: We compared MIBI MPI (cut-off, 45% of maximum pixel count) with a histochemical method in a porcine model, nine controls and eight IP pigs, using 45 min catheter based coronary occlusion of the left anterior descending artery. Infarct size (IS) was determined relative to the area at risk (AAR). The relative infarct size (IS/AAR) after 120 min reperfusion estimated by MPI was 0.83 (0.17) in controls vs 0.07 (0.12) in the IP group (mean (SD), P<0.001). The corresponding values for histochemistry were controls 0.77 (0.19) vs IP 0.07 (0.11), P<0.001. IS/AAR measured by MPI and histochemistry were correlated significantly (r=0.93, P<0.001). Furthermore, IS relative to left ventricular mass (IS/LV) determined by autoradiography and histochemistry correlated (r=0.93, P<0.001). MPI overestimated IS/LV and AAR/LV by approximately a factor of 2 compared with histochemistry or autoradiography. CONCLUSION: MIBI MPI during early reperfusion is a reliable measure of relative infarct size reduction after ischaemic preconditioning, supporting use for stratification for adjunctive therapy and for assessment of prognosis.     

Positive predictive value of 99mTc sestamibi scintimammography in patients with non-palpable,mammographically detected,suspicious, breast lesions

The purpose of this study was to analyse whether the use of Tc sestamibi scintimammography improves the positive predictive value of X-ray mammography. A series of 73 women (median age 51 years, range 35-79 years) with non-palpable, mammographically suspicious, breast lesions was reviewed. There were 41 (56.2%) pre-menopausal, and 32 (43.8%) post-menopausal women. All patients underwent sestamibi scintimammography prior to open breast biopsy. Definitive histology showed breast cancer (pT1a=1 (1.9%), pT1b=47 (90.4%), pT1c=4 (7.7%)) in 52 (71.2%) patients, and benign breast lesions in 21 (28.8%). Patients with cancer were significantly older (P <0.01), while the greatest dimension (size) of the excised lesion did not differ (8.47+/-1.51 vs 8.30+/-1.53 mm; P =0.66) between the two groups. Overall, the positive predictive values of mammography and sestamibi scintimammography were 71.2% and 95.7%, respectively (P =0.004). Patients with false positive mammography were significantly younger than those in whom cancer was diagnosed correctly (45.35+/-7.56 vs 53.96+/-10.60 years; P =0.001), while age did not affect the sensitivity of sestamibi scintimammography, which reached 100% in patients with breast lesions > or =8 mm in size. In this subgroup the positive predictive value of mammography, sestamibi scintimammography, and mammography+sestamibi scintimammography together were 63.4%, 95.1% (P =0.001), and 97.6%, respectively, and the majority of the patients with benign lesions (13 of 15 (86.7%)) could have avoided biopsy. It is concluded that the use of Tc sestamibi scintimammography in conjunction with mammography may potentially reduce unnecessary surgical procedures, and should be performed in all patients with mammographically suspicious breast lesions of 8 mm or greater in size.     

Detection of hibernate myocardium by 99mTc sestamibi gated SPECT during low-dose dobutamine infusion plus nitrate in patients with first acute myocardial infarction

AIM: To investigate the role of Tc-MIBI gated SPECT imaging following the administration of low-dose dobutamine plus nitrate (LDD+nitrate) in the assessment of left ventricular function and the perfusion of hibernate myocardial tissue. METHODS: The study group comprised 29 patients diagnosed as having acute myocardial infarction. In the first month post-infarction, Tc-MIBI gated SPECT imaging was performed in all patients at rest-dobutamine stress and LDD+nitrate. Ejection fraction, end diastolic volume (EDV), end systolic volume (ESV), stroke volume, volume, extent score, and reversibility score values were calculated. RESULTS: The findings of Tc-MIBI gated SPECT imaging following the administration of LDD+nitrate and the rest Tc-MIBI gated SPECT findings revealed that while the levels of ejection fraction (P=0.004) and reversibility score (P=0.000) increased significantly, there was a significant decrease in EDV (P=0.001), ESV (P=0.001), volume (P=0.017), stroke volume (P=0.257) and extent score (P=0.039) values. CONCLUSION: The use of Tc-MIBI gated SPECT concomitantly with the administration of LDD+nitrate is useful in the determination of myocardial hibernation in patients with left ventricular failure following acute myocardial infarction.     

Kinetics of [99mTc]heparin, venous scintigraphy with [99mTc]fibrinogen and beta-thromboglobulin assay in the diagnosis of deep-vein thrombosis

The information provided by three examinations: [99mTc]heparin kinetics (KH), venous scintigraphy with [99mTc]fibrinogen (VSF) and plasmatic assay of beta-thromboglobulin (beta TG), are studied on 23 patients separated into two groups on the basis of phlebographic results. VSF which could provide to a certain extent the same kind of information as phlebography, proves to have insufficient sensitivity. KH has high specificity but low sensitivity, while beta TG performance is the opposite. The authors discuss the mechanisms responsible for these discordant results. They observe that in cases where the KH and beta TG correspond, the diagnostic value is very satisfactory, so that a double positive can replace phlebography in cases where the latter is contra-indicated or difficult to perform.     

Heart tomography with 99mTc sestamibi and echocardiography with dobutamine in the identification of reversible left ventricular dysfunction in patients with acute myocardial infarction]

INTRODUCTION: We investigated the role of technetium-99m (99mTc) sestamibi cardiac imaging and dobutamine echocardiography in detecting myocardial viability early after acute myocardial infarction. MATERIAL AND METHODS: Nineteen patients (mean age 52 +/- 10 years) underwent coronary angiography, low-dose dobutamine echocardiography and rest 99mTc sestamibi imaging within 10 days of myocardial infarction. All patients were revascularized. Resting echocardiogram was repeated 8 months later to evaluate segmental functional recovery. RESULTS: Sixty-one of 108 akinetic or dyskinetic segments at baseline showed functional recovery after revascularization. Sensitivity in predicting segmental functional recovery was 87% for sestamibi imaging and 66% for dobutamine echocardiography (p < 0.001), while specificity and accuracy were comparable. Sestamibi activity was the strongest predictor of segmental functional recovery (p < 0.001). CONCLUSIONS: Dobutamine echocardiography predicts functional recovery after myocardial infarction. However, sestamibi imaging is useful to identify patients with dysfunctional segments without contractile reserve which may benefit by revascularization.     

Assessment of area at risk and efficacy of treatment in patients with acute coronary syndrome using99mTc tetrofosmin imaging in humans

The determination of the myocardium at risk before intervention and the change in that region after intervention constitute a promising measurement tool for the assessment of acute therapy. A new^99mTc labeled myocardial blood flow tracer,^99mTc tetrofosmin, is expected to enable the evaluation of myocardium at risk because of the absence of redistribution. This preliminary study was performed in 9 patients with acute coronary syndrome (4 unstable angina and 5 acute myocardial infarction) to investigate whether recovery of perfusion by tetrofosmin imaging parallels mechanical improvement. Tetrofosmin imaging was performed acutely and 3–30 days later. Visual analysis of defect severity was assessed in both studies. Segments with improvement in perfusion were accompanied by significant wall motion recovery compared with normal and unimproved segments (Δ WMI: normal segments 0.40±0.67, improved segments 1.79±0.68, unimproved segments ?0.15±0.16, p< 0.01 for improved segments compared with other groups), suggesting the efficacy of this tracer for the assessment of the acute therapy. These data suggest that^99mTc tetrofosmin imaging is a useful method for the assessment of the myocardial area at risk and the efficacy of acute therapy in acute myocardial infarction and unstable angina.