F. Philip Anderson

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.

Impact of the troponin standard on the prevalence of acute myocardial infarction

BACKGROUND Recent recommendations are that troponin should replace creatine kinase (CK)-MB as the diagnostic standard for myocardial infarction (MI). The impact of this change has not been well described. Our objective was to determine the impact of a troponin standard on the prevalence of acute non-ST-elevation MI. METHODS The current study was a retrospective analysis of consecutive patients without ST-segment elevation admitted for exclusion of myocardial ischemia to an inner city urban tertiary care center. All patients underwent serial marker sampling (CK, CK-MB, and cardiac troponin I [cTnI]). Patients with ST elevation consistent with acute MI (n = 130) or who did not have an 8 hour cTnI (n = 124) were excluded. The impact of 3 different cTnI diagnostic values were examined in 2181 patients: the lower limit of detectability (LLD); an optimal diagnostic value (OPT), chosen using receiver operator characteristic curve analysis; and the manufacturers suggested upper reference level (URL), when compared to a gold standard CK-MB MI definition. In addition, MI prevalence was assessed using different CK-MB MI definitions and evaluated in patients with ischemic changes only. RESULTS The prevalence CK-MB MI was 7.8%. Using the various cTnI diagnostic values, the incidence of MI increased the prevalence by 28% to 195%. Using the optimal diagnostic value for cTnI, patients with cTnI elevations not meeting CK-MB MI criteria had an intermediate 30-day mortality (5.4%) compared to those with CK-MB MI (7.1%). Grouping the cTnI positive, CK-MB MI negative patients with the CK-MB MI patients rather than the non-CK-MB MI patients reduced mortality for both the MI (to 5.9%) and non-MI groups (from 1.9% to 1.6%). CONCLUSIONS Changing to a troponin standard will have a substantial impact on the number of patients diagnosed with MI. The revised definition for MI will have important clinical and health care implications.

Use of the combination of myoglobin and CK-MB mass for the rapid diagnosis of acute myocardial infarction

Early identification of patients presenting with myocardial infarction (MI) is necessary for rapid initiation of treatment. Currently, MI has been diagnosed using the combination of the history, electrocardiogram (ECG), and biochemical markers of myocardial necrosis. Unfortunately, all lack sufficient sensitivity and specificity to confidently identify most patients with MI in a timely enough fashion to influence early intervention. Development of newer immunochemical assays for CK-MB mass and myoglobin have allowed for earlier, more rapid diagnosis; however, each has important limitations. The diagnostic sensitivity of CK-MB mass, myoglobin, and the combination of both were analyzed at the time of presentation (0 hours) and again 4 hours later in 101 patients admitted from the emergency department (ED) with possible MI. Twenty patients were subsequently diagnosed as having MI. The sensitivity of the initial ECG was 60%, compared with the sensitivities of the initial myoglobin and CK-MB mass of 70% and 30%, respectively. By 4 hours the sensitivity of myoglobin had increased to 85% and CK-MB mass to 90%. The combination of the initial myoglobin and CK-MB mass had a sensitivity of 85%. Combining these two markers, using both the initial and 4-hour samples, raised the sensitivity to 100%, with a specificity of 100% and negative predictive value of 100%. When patients with diagnostic ECGs were excluded, the sensitivity of the combination at 0 hours was 80% with a specificity of 84%, while the use of the 0- and 4-hour markers had a sensitivity and specificity of 100% and 100%, respectively. We conclude that the combination of CK-MB mass and myoglobin can rapidly diagnose or exclude MI in as short as 4 hours after ED presentation, and accuracy is not different in patients without diagnostic ECGs. Application of this strategy could potentially lead to more rapid intervention in patients with MI, while also allowing early identification of lower risk patients.

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.

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.

Utility of Troponin I in Patients with Cocaine‐associated Chest Pain

UNLABELLED Baseline electrocardiogram abnormalities and market elevations not associated with myocardial necrosis make accurate diagnosis of myocardial infarction (MI) difficult in patients with cocaine-associated chest pain. Troponin sampling may offer greater diagnostic utility in these patients. OBJECTIVE To assess outcomes based on troponin positivity in patients with cocaine chest pain admitted for exclusion of MI. METHODS Outcomes were examined in patients admitted for possible MI after cocaine use. All patients underwent a rapid rule-in protocol that included serial sampling of creatine kinase (CK), CK-MB, and cardiac troponin I (cTnI) over eight hours. Outcomes included CK-MB MI (CK-MB >or= 8 ng/mL with a relative index [(CK-MB x 100)/total CK] >or= 4, cardiac death, and significant coronary disease (>or=50%). RESULTS Of the 246 admitted patients, 34 (14%) met CK-MB criteria for MI and 38 (16%) had cTnI elevations. Angiography was performed in 29 of 38 patients who were cTnI-positive, with significant disease present in 25 (86%). Three of the four patients without significant disease who had cTnI elevations met CK-MB criteria for MI, and the other had a peak CK-MB level of 13 ng/mL. Sensitivities, specificities, and positive and negative likelihood ratios for predicting cardiac death or significant disease were high for both CK-MB MI and cTnI and were not significantly different. CONCLUSIONS Most patients with cTnI elevations meet CK-MB criteria for MI, as well as have a high incidence of underlying significant disease. Troponin appears to have an equivalent diagnostic accuracy compared with CK-MB for diagnosing necrosis in patients with cocaine-associated chest pain and suspected MI.

Antibody properties for chemically reversible biosensor applications

Abstract A recently reported fiber-optic sensor based on a homogeneous fluorescence energy-transfer immunoassay operates in a continuous, reversible manner to quantify the anticonvulsant drug phenytoin (5,5-diphenylhydantoin). The chemical kinetics of the two simultaneous antibody-hapten (analyte) and antibody-hapten (labeled indicator) reactions in the sensor are now modeled mathematically. Simulation shows that the chemical response time is controlled by the dissociation rate constant and is independent of the association rate constant, and that an equalibrium chemical response can be achieved in minutes. The sensitivity and dynamic range of the analyte concentration which can be measured depends on the ratio of dissociation rate constants for the labeled and unlabeled hapten reactions, and on the total concentration of reactants in the sensor. The relative concentration ratios of antibody to labeled hapten has little impact on the sensitivity or dynamic range of the system, but can be optimized to provide the maximum amount of labeled hapten availble for instrumental measurement.

Post-column reaction detection of biotin in human plasma ultrafiltrate based on laser-induced fluorescence energy transfer in the far-red spectral region

High performance liquid chromatography followed by post-column reaction detection in the far-red spectral region provides added sensitivity and selectivity. A homogeneous fluorescence energy transfer assay in the competitive mode based on the binding of biotin and streptavidin was developed as an on-line post-column reaction detection system. The labels used for energy transfer were R-Phycoerythrin conjugated to biotin and Cyanine 5 labeled with streptavidin. The energy transfer peak was measured at 670 nm and excitation was achieved using the 488 nm line of an argon ion laser. The biotin concentration in plasma ultrafiltrate ranged from 0.024 to 6.12 ng/mL (n = 6). The precision of the two controls, 0.24 and 2. 44 ng/mL, was found to be 18.70% and 9.92% relative standard deviation respectively. Accuracy was 10.47% and 1.95% difference from spiked, respectively (n = 6). The limit of detection was 21.70 pg/mL (8.90 x 10(-11)M) calculated based on a factor of 2x the standard deviation of the blank (n = 6). The correlation coefficient for the calibration curve was found to be 0.9995. Recovery from plasma ultrafiltrate at 2.44 ng/mL was 103.40% (n = 6). Detection selectivity was indicated by the absence of background fluorescence in six different plasma samples collected from six individual donors. Endogenous levels were detected in two of the six pools of plasma ultrafiltrates.