The utility of four biochemical markers in the triage of chest pain patients.

Four biochemical markers, creatine kinase (CK)-MB isoenzyme, myoglobin, myosin light chains and troponin I, were studied in 1,338 patients presenting to the emergency department with chest pain suggestive of coronary artery disease (CAD). One hundred and eighty-seven patients had an acute myocardial infarction (MI). At least one of the four markers was over the threshold on the first sample in 78% of MI patients, as compared to only 40% with an elevated CK-MB. After 4 h, 88% had at least one marker elevated. None of the 69 patients with atypical chest pain, no history of CAD, no markers over threshold on the first sample and a normal electrocardiogram had an acute MI or unstable angina. If we had discharged this group, we would have saved USD 264,000, estimating a cost of USD 2,000 per day. Using four biochemical markers improved the early diagnosis of CAD and may help identify groups suitable for early discharge.

Serial use of bedside CKMB/myoglobin device to detect acute myocardial infarction in emergency department chest pain patients.

A qualitative bedside device (Spectral Diagnostics, Toronto, Canada) for CKMB and myoglobin (MYOG) detection was evaluated in emergency department (ED) patients with chest pain to determine performance characteristics. At presentation (0 h) and at three hours (3 h), serum was analyzed in the ED with results considered positive if either 0-h or 3-h CKMB or MYOG bands were visible. The results were compared with the diagnosis of myocardial infarction (MI) per hospital discharge diagnosis (n = 132, 87%) or telephone follow-up (n = 19; 1 patient lost to follow-up). Of 151 study patients, 30 (20%) were diagnosed with MI; all were admitted to hospital. On electrocardiogram (EKG), 17 (57%) MI patients had ST-segment elevation. At 0-h, 26 of 30 (87%) MI patients were positive for CKMB/MYOG. By 3 h, 21 of 23 (91%) MI patients were positive for CKMB/MYOG; 7 MI patients were already admitted to hospital. Combining 0-h and 3-h results, the device sensitivity for MI was 93% (28/30) with specificity of 54%. Combining device results plus diagnostic EKG, sensitivity was found to be 100% (30/30). If the device result was positive, then the odds ratio for having an ischemic complication was 6.5. We conclude that the CKMB/MYOG device identified most MI patients at ED presentation and 3 h later. Combining device results with EKG detected all MI patients in the ED.

Effect of recent cocaine use on the specificity of cardiac markers for diagnosis of acute myocardial infarction.

We evaluated whether recent cocaine use alters the specificity of CK-MB, myoglobin, and cardiac troponin I for acute myocardial infarction (AMI) in patients who are seen in the emergency department for chest pain. Patients <60 years old with potential myocardial ischemia underwent a standardized history and physical examination and routine CK-MB assays every 8 to 12 hours and had study serum obtained at presentation for CK-MB, myoglobin, and cardiac troponin I immunoassays, as well as benzoylecgonine, cocaine's main metabolite. We enrolled 97 patients, 19 (20%) of whom had recent used cocaine. Patients with and without cocaine use were similar with regards to sex, race, renal and muscular disease, diabetes, family history, and hypertension and rate of AMI (12% vs 11%, p = 1.0). In patients without MI, the mean myoglobin level was higher in cocaine users than noncocaine users (179 vs 74 ng/ml; Mann-Whitney p = 0.003), but the mean values were similar for CK-MB (2.2 vs 2.1 ng/ml; Mann-Whitney p = 0.58) and for cardiac troponin-I (0.02 vs 0.02 ng/ml; Mann-Whitney p = 0.87). The specificities of the markers in patients with and without cocaine use were as follows: cardiac troponin I, 94% vs 94%, (p = 1.0); CK-MB, 75% vs 88% (p = 0.24); and myoglobin, 50% vs 82%, (p = 0.02), respectively. Our data demonstrate that the specificity of myoglobin was altered by recent cocaine use. The specificity of CK-MB was affected less and the specificity of cardiac troponin I was not affected by recent cocaine use.

Analytical performance and clinical utility of a sensitive immunoassay for determination of human cardiac troponin I.

OBJECTIVES: To determine the serum and plasma level of human cardiac troponin I (cTnI) resulting from myocardial damage, we have developed a sensitive and specific one-step enzyme immunoassay to measure cardiac troponin I. DESIGN AND METHODS: The COBAS cTnI assay is a semi-automated one-step solid phase immunoassay compatible with the COBAS Core. The assay is performed in a sandwich type format using a polyclonal goat antibody capture and two highly specific horseradish peroxidase conjugated monoclonal antibody detectors directed against different epitopes of the cTnI molecule. Calibrators were made with purified recombinant cTnI. RESULTS: The level of cTnI was determined in 84 healthy donors with no evidence of myocardial injury, resulting in a lower limit of detection (LLD) of 0.09 microgram/L. The upper reference limit (URL) of the normal reference range was calculated as 0.20 microgram/L. The dynamic range of the consequent EIA was between 0.09 and 6.0 micrograms/L with a total assay time of 45 min. Intra-assay and inter-assay variances (CVs) were < or = 4%. Cross-reactivity with fast and slow skeletal troponin I was absent in concentrations up to 2.0 mg/L. Common interferents yielded negative results in the cTnI assay. Clinical utility was confirmed by measuring the circulating serum or plasma levels of cardiac troponin I in serial samples from marathon runners, clinical samples from trauma patients, and patients presenting to the Emergency Department with complaints of chest pain. Results were further evaluated using clinical diagnosis at discharge and quantified concentrations of other cardiac markers by a Stratus analyzer and ELISA procedures. CONCLUSIONS: Results from normal and clinical samples assayed in house for cTnI concentrations indicate that the Spectral EIA is a highly sensitive means of quantifying cTnI levels in serum and plasma for acute cardiac syndrome. The cardiac specificity of cTnI over other well-known cardiac markers is reflected in experimental results and parallel clinical diagnosis.

Evaluation of cardiac STATus CK-MB/myoglobin device for rapidly ruling out acute myocardial infarction.

The Cardiac STATus CK-MB/Myoglobin device is highly sensitive and has a high negative predictive value within 3 hours of patient presentation. The device may play a role in the re-triage of patients from the CCU to less intensive settings, resulting in a net cost savings.

Use of enzyme immunoassay for measurement of skeletal troponin-I utilizing isoform-specific monoclonal antibodies.

OBJECTIVE: To determine the serum level of fast skeletal troponin I (fsTnl) resulting from skeletal muscle damage, we have developed a sensitive two-site enzyme immunoassay to measure skeletal troponin I. DESIGN AND METHODS: Twelve monoclonal antibodies were raised against human fsTnl. Of these antibodies, 8 were fsTnl-specific and the remaining 4 reacted with both skeletal and cardiac troponin I (cTnl). Two monoclonals were utilized for a development of this fsTnl immunoassay. Standards were made with purified recombinant human fsTnl for the range of 0-25 micrograms/mL. RESULTS: Total assay variance (CV) ranged from 1.7% to 9.6%. The upper limit of the normal reference range was established as 0.2 microgram/L by determining fsTnl concentration in sera of 108 healthy donors without evidence of muscle damage. Purified human cTnl up to 500 micrograms/L and cTnl-positive clinical serum samples yielded negative results in the fsTnl assay. The serum levels of fsTnl were determined in trauma patients, patients with chronic degenerative muscle disease, and marathon runners. In the study populations, the serum levels of fsTnl were correlated with other biochemical markers that are traditionally used to monitor striated muscle damage. CONCLUSIONS: In the present preliminary studies, measuring the serum levels of fsTnl in patients with various forms of muscle damage is more accurate than using the classical non muscle-specific biochemical markers.