Comparison of myocardial perfusion imaging and cardiac troponin I in patients admitted to the emergency department with chest pain.

BACKGROUND: Identification of patients with acute coronary syndromes (ACS) among those who present to emergency departments with possible myocardial ischemia is difficult. Myocardial perfusion imaging with 99mTc sestamibi and measurement of serum cardiac troponin I (cTnI) both can identify patients with ACS. METHODS AND RESULTS: Patients considered at low to moderate risk for ACS underwent gated single-photon emission CT sestamibi imaging and serial myocardial marker measurements of creatine kinase-MB, total creatine kinase activity, and cTnI over 8 hours. Positive perfusion imaging was defined as a perfusion defect with associated abnormalities in wall motion or thickening. cTnI >/=2.0 ng/mL was considered abnormal. Among the 620 patients studied, 59 (9%) had myocardial infarction and 81 (13%) had significant coronary disease; of these patients, 58 underwent revascularization. Perfusion imaging was positive in 241 patients (39%), initial cTnI was positive in 37 (6%), and cTnI was >/=2.0 ng/mL in 74 (12%). Sensitivity for detecting myocardial infarction was not significantly different between perfusion imaging (92%) and cTnI (90%), and both were significantly higher than the initial cTnI (39%). Sensitivity for predicting revascularization or significant coronary disease was significantly higher for perfusion imaging than for serial cTnI, although specificity for all end points was significantly lower. Lowering the cutoff value of cTnI to 1.0 ng/mL did not significantly change the results. CONCLUSIONS: Early perfusion imaging and serial cTnI have comparable sensitivities for identifying myocardial infarction. Perfusion imaging identified more patients who underwent revascularization or who had significant coronary disease, but it had lower specificity. The 2 tests can provide complementary information for identifying patients at risk for ACS.

Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain.

OBJECTIVES: This study sought to determine the ability of early perfusion imaging using technetium-99m sestamibi to predict adverse cardiac outcomes in patients who present to the emergency department with possible cardiac ischemia and nondiagnostic electrocardiograms (ECGs). BACKGROUND: Evaluation of patients presenting to the emergency department with possible acute coronary syndromes and nondiagnostic ECGs is problematic. Accurate risk stratification is necessary to prevent serious adverse outcomes. Initial results suggest that early perfusion imaging using technetium-99m sestamibi enables reliable risk stratification. METHODS: Patients presenting to the emergency department with a low to moderate probability of acute coronary syndromes underwent rapid sestamibi injection with gated single-photon emission computed tomographic imaging. Studies showing perfusion defects with associated wall motion abnormalities were considered positive. RESULTS: A total of 532 consecutive patients underwent serial myocardial marker analysis and rest perfusion imaging. Of these patients, perfusion imaging was positive in 171 (32%). Positive perfusion imaging was the only multivariate predictor of myocardial infarction (MI) (p < 0.0001, odds ratio [OR] 33, 95% confidence interval [CI] 7.7 to 141) and was the most important independent predictor of MI or revascularization (p < 0.0001, OR 14, 95% CI 7.3 to 25), followed by diabetes (p < 0.01, OR 2.8, 95% CI 1.5 to 5.1), typical angina (p = 0.01, OR 2.1, 95% CI 1.2 to 3.7) and male gender (p = 0.03, OR 1.9, 95% CI 1.1 to 3.5). The sensitivity of positive perfusion imaging for MI was 93% (95% CI 77% to 98%), and for MI or revascularization it was 81% (95% CI 71% to 88%), with negative predictive values of 99% (95% CI 98% to 100%) and 95% (95% CI 92% to 97%), respectively. CONCLUSIONS: Positive rest perfusion imaging accurately identified patients at high risk for adverse cardiac outcomes, whereas negative perfusion imaging identified a low risk patient group. Early perfusion imaging allows for rapid and accurate risk stratification of emergency department patients with possible cardiac ischemia and nondiagnostic ECGs.

Ability of troponin I to predict cardiac events in patients admitted from the emergency department.

OBJECTIVES: We sought to determine the predictive ability of troponin I (TnI) in a heterogeneous group of patients with chest pain admitted from the emergency department (ED) for exclusion of myocardial infarction (MI). BACKGROUND: Previous studies in high-risk patients demonstrated that troponin elevations are associated with increased cardiac events. Little information is available on its predictive ability in more heterogeneous, lower risk patients. METHODS: Consecutive patients admitted from the ED for possible MI underwent serial myocardial marker sampling of TnI and creatine kinase, CK-MB over an 8-h period. Patients with ST segment elevation were excluded. End points included MI, death, significant complications (e.g., cardiac or respiratory arrest, intra-aortic balloon pump, pulmonary artery catheter or pacemaker placement, revascularization or inotropic infusion) and significant disease. RESULTS: Events occurred in 513 (27%) of the 1,929 patients evaluated: MI in 175 (9.1%) and death in 34 (1.8%); an additional 248 patients (13%) without MI had complications, and 323 (17%) without MI had significant disease. Sensitivity of TnI for MI was high (96%). Patients without MI who were TnI-positive were more likely to have complications (43% vs. 12%) or significant disease (41% vs. 17%) as compared with those who were TnI-negative; however, the sensitivity of TnI for these two end points was low (14% and 21%, respectively). Predictive values were unchanged after excluding patients with ischemic electrocardiograms. CONCLUSIONS: Troponin I had a high sensitivity for MI when used as part of a rapid rule-in protocol; however, the sensitivity for other end points was low. Use of TnI alone failed to identify the majority of patients who had either significant disease or complications.

Radionuclide bone imaging findings in recurrent calvarial infarction in sickle cell disease.

A patient with sickle cell disease developed bi-parietal calvarial infarctions, and subsequently developed bi-frontal calvarial infarctions. The findings on [99mTc]MDP bone imaging showed decreased activity in the parietal and frontal regions during the phase of acute infarction and increased activity in the parietal region during the later healing phase. Thus the findings on radionuclide bone imaging in cortical infarcts will depend upon the stage of the condition.

Myocardial perfusion imaging using thallium-201: a new algorithm for calculation of background activity.

A method is presented for calculating a background image to be subtracted from TI-201 myocardial perfusion images. The method was derived from experimental measurements of background components in which hearts of animals injected with TI-201 were replaced with hearts from nonradioactive animals. The algorithm generates a background image that accounts for TI-201 activity in surrounding tissues and within the cardiac chamber. Comparison of the computer-generated background images with background images of the experimental models showed a mean difference of about 3% (range 1-6%). Clinical images using this method of background generation and subtraction are presented.

Thallium-201/technetium-99m-RP-30A disparity in the course of myocardial infarction after attempted reperfusion.

Recent reports have established that 201Tl may be taken up in areas of recent myocardial infarction after myocardial blood flow is re-established. In addition, there is accelerated 201Tl "washout" from these regions producing a pattern of "reverse redistribution." We present a case in which these phenomena may have contributed to a disparity of findings between a 201Tl stress imaging study and a repeat stress imaging study performed with a [99mTc] isonitrile (99mTc-RP-30A).

Preparation and evaluation of a 99mTc-SnF2 colloid kit for leukocyte labeling.

Stannous fluoride colloid (SFC) kits for instant radiolabeling with 99mTc were prepared and evaluated for suitability as a leukocyte radiolabeling agent. Technetium-99m labeling for kits stored at -15 degrees C for up to 3 mo was greater than 95% as determined by instant thin layer chromatography while colloid particles of 1-3 microns were measured by electron microscope for these preparations. Canine leukocyte preparations labeled with [99mTc]SFC and characterized by triple density gradients of metrizamide in plasma demonstrated an 83% leukocyte association. Analysis of labeled cell preparation for up to 3 hr demonstrated label stability. Labeled leukocytes, when readministered in normal dogs, demonstrated bi-exponential blood clearance with uptake and subsequent clearance from lung. There was increasing uptake of labeled leukocytes by the liver until steady state was achieved. Furthermore, when whole blood samples were analyzed by the triple density gradient method, an increasing monocyte-to-granulocyte ratio was observed to occur with time. By 3 hr 95% of the whole blood activity was associated with the leukocyte fraction. Dogs in which a 24-hr sterile abscess was created demonstrated elevated blood-pool activity as compared to control with localization of the labeled cells at inflammatory sites within 3 hr following cell readministration.

Early diagnosis of acute myocardial infarction in patients without ST-segment elevation.

Early identification of acute myocardial infarction (AMI) is necessary to initiate appropriate treatment. In patients presenting without ST-segment elevation, diagnosis is often dependent on the presence of elevated myocardial markers. This study examines the ability of serial MB mass alone and in combination with myoglobin in diagnosing AMI in patients without ST-segment elevation within 3 hours of presentation. In all, 2,093 patients were admitted and underwent serial marker analysis using myoglobin, creatine kinase (CK), and CK-MB at 0, 3, 6, and 8 hours. AMI was diagnosed by a CK-MB > or =8.0 ng/ml and a relative index (RI) (CK-MB x 100/total CK) > or =4.0. A total of 186 patients (9%) were diagnosed with AMI. The optimal diagnostic strategy was an elevated CK-MB + RI on the initial or 3-hour sample or at least a twofold increase in CK-MB without exceeding the upper range of normal over the 3-hour time period (sensitivity 93%, specificity 98%). The combination of an elevated CK-MB + RI or myoglobin on the initial or 3-hour sample had a sensitivity of 94%, although specificity was significantly lower, at 86%. Sensitivities and specificities after exclusion of the 242 patients with ischemic electrocardiographic changes were essentially unchanged. We conclude that most patients with AMI presenting with nondiagnostic electrocardiograms can be diagnosed within 3 hours of presentation.

Radionuclide evaluation of lung trauma.

Nuclear medicine imaging procedures can play a significant role in evaluating the pulmonary complications that are seen in trauma patients. A quantitative method for measuring increased pulmonary capillary permeability that uses Tc-99m HSA allows early diagnosis of acute respiratory distress syndrome (ARDS) and accurately differentiates this condition from pneumonia or cardiogenic pulmonary edema. This technique may be of great value in following the response to therapy. The use of 133Xe to diagnose inhalation injury remains an important diagnostic tool, particularly at hospitals with specialized burn units. Regional decreases in ventilation-perfusion images reliably localize aspirated foreign bodies. Radionuclide techniques that are used to demonstrate gastropulmonary aspiration remain controversial and require further clinical evaluation. Pulmonary perfusion imaging, although nonspecific, may provide the earliest clue for correct diagnosis of fat embolism, air embolism, contusion, or laceration. Furthermore, the possibility of perfusion abnormality due to these uncommon conditions must be remembered whenever trauma patients are evaluated for pulmonary thromboembolism with scintigraphy. Occasionally, liver or spleen scintigraphy may be the most appropriate procedure when penetrating chest trauma also involves these subdiaphragmatic organs.

Pulmonary artery thrombus detection by magnetic resonance imaging.

We report a patient in whom cardiac magnetic resonance imaging detected a clinically unsuspected pulmonary artery thromboembolus. Follow-up MRI after surgical removal of the thromboembolus showed normal pulmonary arteries. This case illustrates the potential utility of MRI in the detection and follow-up of central pulmonary artery thromboembolism.

Radioiodination of biologically active compounds: a simplified solid-state enzymatic procedure.

A simplified solid-state enzymatic iodination procedure for routine labeling of unstable pure protein or complex amino acid-containing molecules is presented. The procedure was designed using agarose-bound lactoperoxidase to iodinate human IgG with iodine-125. This method consistently resulted in a labeling efficiency greater than 90% with high stability and undetectable gross structural alterations of the substrate as evaluated by immunodiffusion and electrophoresis. The technique presented is simple, efficient, and may be employed to yield a sterile, pyrogen-free labeled species.

Single isotope evaluation of pulmonary capillary protein leak (ARDS model) using computerized gamma scintigraphy.

Using a canine oleic acid model, a computerized gamma scintigraphic technique was evaluated to determine 1) ability to detect pulmonary capillary protein leak in a model temporally consistent with clinical adult respiratory distress syndrome (ARDS), 2) the possibility of providing a quantitative index of leak, and 3) the feasibility of closely spaced repeat evaluations. Study animals received oleic acid (controls, n = 10; 0.05 ml/kg, n = 10; 0.10 ml/kg, n = 12; 0.15 ml/kg, n = 6) 3 hours prior to a tracer dose of technetium-990m (99mTc) HSA. One animal in each dose group also received two repeat tracer injections spaced a minimum of 45 minutes apart. Digital images were obtained with a conventional gamma camera interfaced to a dedicated medical computer. Lung: heart ratio versus time curves were generated, and a slope index was calculated for each curve. Slope index values for all doses were significantly greater than control values (P(t) less than 0.0001). Each incremental dose increase was also significantly greater than the previous dose level. Oleic acid dose versus slope index fitted a linear regression model with r = 0.94. Repeat dosing produced index values with standard deviations less than the group sample standard deviations. We feel this technique may have application in the clinical study of pulmonary permeability edema.

Effects of pulmonary vascular recruitment on gamma scintigraphy and pulmonary capillary protein leak.

Pulmonary vascular recruitment (PVR) was altered and lung-heart radioactivity ratio (L:H) measured using 99mTc-tagged human serum albumin (Tc-HSA) in five dogs each by inflating a left atrial balloon (LAB) to produce a 20 mm Hg pulmonary capillary wedge pressure (PCWP) or opening a 5 mm diameter aortoinferior caval shunt (ACS) before and after oleic and injury. Cardiac output (CO), pulmonary arterial pressure (PAP), and PCWP were measured with each alteration in PVR. In an additional 10 dogs, multiple doses of Tc-HSA, administered over 5 hours, 2 hours after 0.1 ml/kg oleic acid, produced parallel "slopes of injury" over the 5-hour period. Each rise in PVR was associated with an acute increase in L:H but demonstrated no significant increase in slope after equilibration. Closure of the ACS or LAB deflation returned the L:H to projected baseline. A "slope of injury" (P less than 0.001) was seen after the administration of oleic acid, which was significantly (P less than 0.01) steeper with an increased PVR. This was confirmed by repeat doses of Tc-HSA. This study confirmed the following hypotheses: (1) the "slope of injury" curves were reproducible so that the effects of experimental interventions on the rate of protein leak could be determined; (2) the L:H rapidly became constant after an acute change in PVR prior to oleic acid injury: and (3) a raised PVR would increase the rate of albumin leak after pulmonary microvascular injury.

Successful treatment of adult respiratory distress syndrome by histamine and prostaglandin blockade in a porcine Pseudomonas model.

Porcine Pseudomonas adult respiratory distress syndrome (ARDS) has been shown to respond to combination therapy of 150 mg of cimetidine, 12.5 mg/kg of ibuprofen, 10 mg/kg of diphenhydramine, 0.2 mg/kg of ketanserin, and 30 mg/kg of methylprednisolone (CIDKM or Poly-5) given at 20 and 120 minutes after the onset of a continuous infusion of liver Pseudomonas aeruginosa, 5 X 10(8) colony-forming units (CFU) ml at 0.3 ml/20 kg/min. The present study was designed to determine the minimal, effective therapy by selective deletion of individual agents from CIDKM. Eight groups were studied: saline control (S, n = 9), Pseudomonas control (P, n = 8), and the following Pseudomonas plus treatment groups (each n = 5): CIDKM (cimetidine, ibuprofen, diphenhydramine, and ketanserin), CID (cimetidine, ibuprofen, and diphenhydramine), IC (ibuprofen and cimetidine), ID (ibuprofen and diphenhydramine), and CD (cimetidine and diphenhydramine). Pseudomonas alone produced severe ARDS with significant (p less than .05) decreases in PAO2 cardiac index, and systemic arterial pressure and significant increases in pulmonary artery pressure, extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux measured as slope index (SI). Full therapy, CIDKM or Poly-5, showed significant improvement in all parameters. Deletion of methylprednisolone did not significantly effect any parameter measured. The deletion of ketanserin, leaving CID, did not alter treatment efficacy, except for a significant decline in cardiac index at 3 hours. Deletion of ibuprofen from CID resulted in a failure to reverse pulmonary arterial hypertension, hypoxemia, elevated EVLW, and increased SI. Removal of either cimetidine or diphenhydramine from CID resulted in significant increases in EVLW compared with control levels and SI compared with both control levels and CID. These results indicate that a combination of both histamine H1 and H2 receptor blockers and the cyclooxygenase inhibitor, ibuprofen, is effective and essential in the treatment of hypoxemia, early pulmonary hypertension, and pulmonary microvascular injury in this fulminant model of porcine Pseudomonas ARDS.

Gamma scintigraphic analysis of albumin flux in patients with acute respiratory distress syndrome.

Computerized gamma-scintigraphy provides a new method for the analysis of albumin flux in patients with pulmonary permeability edema. In this technique, 10 mCi of 99mTc -tagged human serum albumin is administered and lung:heart radioactivity ratios are determined. This ratio remains constant unless there is a leak of albumin, when a rising ratio with time, called the "slope index" (SI), is seen. Thirty-five scintigraphic studies were obtained in 28 patients by means of a portable computerized gamma-camera. Thirteen of these patients had clinical evidence of the acute respiratory distress syndrome (ARDS) and six had or were recovering from left ventricular induced congestive heart failure (CHF). Five of the patients with CHF and pulmonary capillary wedge pressure (PCWP) below 30 mm Hg had normal scintigraphic studies. One patient in florid CHF with a PCWP of 40 mm Hg had a positive SI of 1.6 X 10(-3) U/min. The patients with ARDS were found to have significantly higher SIs than patients who did not have, or had recovered from, ARDS. The arterial:alveolar oxygen tension ratio (a/A)O2 was 0.30 +/- 0.14 in patients with positive SIs while receiving 11.0 +/- 6.8 m H2O positive end-expiratory pressure (PEEP). Both the (a/A)O2 and level of PEEP were significantly (P less than 0.01) worse in these patients than in patients with normal SIs. Positive SIs were present from 1 to 8 days following the apparent onset of ARDS in seven studies in five patients. Recovery of gas exchange was associated with a return to a normal SI in four patients. In conclusion, computerized gamma-scintigraphy was a sensitive, noninvasive tool for the detection of a pathologic increase in pulmonary protein flux. Positive scintigraphic findings were associated with significantly impaired gas exchange. The method documented that the leak of albumin in patients with ARDS may last for days but resolves with recovery.

Failure of methylprednisolone, ibuprofen, or prostacyclin to reduce HCl-induced pulmonary albumin leak in dogs.

The purpose of this study was to examine the effects of methylprednisolone (MP), ibuprofen (I), and prostacyclin (PGI2) pretreatment on cardiopulmonary hemodynamics, arterial oxygenation, and pulmonary alveolar-capillary membrane permeability, measured with a gamma-scintigraphic technique, after acid instillation in the dog. All animals were placed on their right side and 2 ml/kg 0.1 N HCl was instilled into the endotracheal tube. Five untreated control dogs showed a significant (p less than 0.05) rise in slope index (SI), a scintigraphic measurement of pulmonary albumin flux, 30 minutes after acid injury. After 120 minutes there was a significant rise in mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) and a decrease (p less than 0.05) in cardiac output (CO) and PaO2. Two groups of five dogs each were pretreated with MP (30 mg/kg) and I (12.5 mg/kg), respectively. Thirty minutes after acid instillation both groups showed a significant rise in the SI, which was significantly greater than the values in the control animals in the case of MP. By 120 minutes after acid injury all changes in PAP, PVR, PaO2, and CO were not significantly different from those of control animals with the exception of the I group, which resisted any change in CO throughout the study. Another group of five dogs were pretreated with a constant infusion of PGI2 (3 micrograms/kg/min) starting 75 minutes before acid instillation. PGI2 produced a significant increase in CO that was also greater (p less than 0.05) than the CO in control animals before instillation of HCl. Pre-HCl SI in the dogs treated with PGI2 was slightly, but significantly, increased over control dogs. The SI and CO remained significantly higher than values in control animals 30 minutes after acid injury. The SI remained significantly higher than that of control animals at 120 minutes. After 2 hours changes in PAP, PVR, PaO2, and CO were without significant difference from those of control animals. These data support the conclusion that PGI2, I, or MP are not effective therapy for acid aspiration and that PGI2 and I may worsen the protein leak by increasing flow across the damaged capillary membrane.

Pulmonary compliance: early assessment of evolving lung injury after onset of sepsis.

We compared the sensitivity of dynamic (Cdyn) and static lung compliance (CL) with indicators of permeability injury in a model of septic porcine adult respiratory distress syndrome. Two groups of anesthetized ventilated swine (15-25 kg) were studied. Septic animals (Ps, n = 13) received Pseudomonas aeruginosa intravenously for 1 h, which resulted in severe adult respiratory distress syndrome. Controls (C, n = 13) received 0.9% NaCl. Cdyn, CL, bronchoalveolar lavage for protein estimation, and thermal cardiogreen extravascular lung water (EVLW) measurements were performed in seven C and eight Ps animals. Six C and five Ps animals underwent gamma camera measurement of lung-to-heart ratio (slope index) of 99Tc-labeled human serum albumin. Both Cdyn and CL decreased significantly (P less than 0.01) at 30 min and thereafter in Ps vs. C. EVLW, slope index, and bronchoalveolar protein content increased significantly (P less than 0.05) in Ps vs. C at 120, 150, and 300 min, respectively. Cdyn and CL decreased well before onset of permeability injury. These early changes may be due to release of vasoactive mediators and sequestration of neutrophils in the pulmonary capillaries and later to increases in EVLW. Measurement of Cdyn and CL represents an early means of assessing evolving lung injury in this acute septic porcine model.

Cervical distribution of iodine 131 following total thyroidectomy for thyroid cancer.

The use of postoperative radioiodine thyroid scanning has questioned whether total thyroidectomy is surgically possible. Similar to earlier studies, we have found functioning iodine 131 (131I)-avid thyroid tissue in our patients following total thyroidectomy for thyroid cancer. Preoperative and postoperative thyroid scans were compared in 24 patients to study the cervical location of postthyroidectomy residual thyroid tissue. Thyroid scanning detected 44 distinct sites of uptake. Thirty-eight of these foci were located either at the extremes of the upper poles of the thyroid gland (24) or along the embryonic thyroid descent tract (14). We conclude that these foci of 131I uptake represent incomplete resection of normal thyroid tissue, and that surgical attention to these areas should result more frequently in extirpation of the entire thyroid gland.

Comparison of indium 111-labeled platelets v leukocytes in a pyogenic abscess.

This study sought to determine which blood component, WBCs or platelets, is the more specific indicator of an abscess and where each localizes. An abscess was created using stool in the hind limb of dogs. After 24 hours, one group was given autologous indium 111-labeled platelets and another group was given autologous indium 111-labeled WBCs. Blood, abscess fluid, infected operative control muscle tissue, and nonoperative control muscle tissue were counted for radioactivity 24 hours after administration of the labeled cells. There was significantly (P less than .001) less WBC radioactivity in blood and more within abscess fluid compared with platelets. The highest platelet activity occurred in muscle tissue adjacent to the abscess (P less than .002) compared with platelet activity in abscess fluid or control muscle tissue. The unwanted high platelet blood background activity and the desirable high concentration of WBC radioactivity within the abscess fluid makes the latter the preferential radionuclide imaging agent.

Gamma scintigraphic localization of platelets labeled with indium 111 in a focus of infection.

To determine if autologous platelets would localize in a focus of infection, a pyogenic abscess was created in the left hind limb of dogs, using previously processed human stool, while an identical surgical procedure without bacterial inoculation was performed on the right hind limb. Autologous platelets labeled with indium 111 (500 microCi) were administered intravenously to five control dogs that had not undergone surgery, to eight dogs two hours following stool inoculation, and to five dogs 24 hours after stool inoculation. A statistically significant scintigraphic increase in tracer activity was apparent within 24 hours in each animal at the site of abscess creation. Tissue samples, obtained at 48 hours after the administration of labeled platelets, revealed a significant increase in percent dose of 111In per gram of infected muscle compared with control muscle. These studies show that platelets localize at the site of bacterial infection.