Willie Gerhardt

The prognostic value of serum troponin T in unstable angina.

BACKGROUND Cardiac troponin T is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. We used a newly developed enzyme immunoassay for troponin T to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. METHODS We screened 109 patients with unstable angina (25 with accelerated or subacute angina and 84 with acute angina at rest) for serum creatine kinase activity, creatine kinase isoenzyme MB activity, and troponin T every eight hours for two days after admission to the hospital. The outcomes of interest during the hospitalization were death and myocardial infarction. RESULTS Troponin T was detected (range, 0.20 to 3.64 micrograms per liter; mean, 0.78; median, 0.50) in the serum of 33 of the 84 patients (39 percent) with acute angina at rest. Only three of these patients had elevated creatine kinase MB activity (two were positive for troponin T, and one was negative). Of the 33 patients who were positive for troponin T, 10 (30 percent) had myocardial infarction (3 after coronary-artery bypass surgery), and 5 of these died during hospitalization. In contrast, only 1 of the 51 patients with angina at rest who were negative for troponin T had an acute myocardial infarction (P less than 0.001), and this patient died (P = 0.03). Thus, 10 of the 11 patients with myocardial infarctions had detectable levels of troponin T; only 1 had elevated creatine kinase MB activity. Troponin T was not detected in any of the 25 patients with accelerated or subacute angina, and none of these patients died. CONCLUSIONS Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial-cell injury than serum creatine kinase MB activity, and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina.

Quality Specifications for Cardiac Troponin Assays

Abstract The objective of this report is to help to improve the quality of immunochemical determinations of cardiac troponins. The guidelines are intended for use by the manufacturers of commercial assays and by clinical laboratories performing troponin analyses. The main goals of the document are that: 1. Manufacturers endorse, or at the minimum, address the enclosed recommendations. 2. All package inserts for troponin immunoassay procedures include information on method design, and on pre-analytical and analytical performance characteristics as outlined in this document. 3. Manufacturers and the scientific community select and design research projects that further the knowledge and the definition of the issues addressed in this document.

Evaluation of a point-of-care system for quantitative determination of troponin T and myoglobin.

Abstract We present the results of a multicenter evaluation of a new point-of-care system (Cardiac Reader) for the quantitative determination of cardiac troponin T (CARDIAC T Quantitative test) and myoglobin (CARDIAC M test) in whole blood samples. The Cardiac Reader is a CCD camera that optically reads the immunochemical test strips. The measuring range is 0.1 to 3 μg/l for CARDIAC T Quantitative and 30 to 700 μg/l for CARDIAC M. Both tests are calibrated by the manufacturer. The reaction times of the tests are 12 or 8 minutes, respectively. Method comparisons were performed with 281 heparinized blood samples from patients with suspected acute coronary syndromes. The results obtained with CARDIAC T Quantitative showed a good agreement compared with cardiac troponin T ELISA (r = 0.89; y = 0.93x + 0.02). The method comparison between CARDIAC M and Tina-quant Myoglobin also showed a good agreement between both assays (r = 0.98; y = 0.92x + 1.6). Test lot-to-lot comparisons yielded differences of 2% and 6% for CARDIACT Quantitative and of 0 to 11% for CARDIACM. The within-run imprecision with blood samples and control materials was acceptable for CARDIAC T Quantitative (CV 10 to 15%) and good for CARDIAC M (CV 5 to 10%). The between-instrument CV was below 7% for CARDIACT Quantitative and below 5% for CARDIACM. The cross-reactivity of CARDIAC T Quantitative with skeletal troponin T was approximately 0.003%. No significant analytical interference was detected for any of the assays in investigations with biotin (up to 100 μg/l), hemoglobin (up to 0.125 mmol/l), hematocrit (26 to 52%), bilirubin (up to 340 μmol/l), triglycerides (up to 5.0 mmol/l), and 18 standard drugs. With the Cardiac Reader reliable quantitative results can be easily obtained for both cardiac markers. The system is, therefore, particularly suitable for use in emergency rooms, coronary care units and small hospitals.

Troponin T: A sensitive and specific diagnostic and prognostic marker of myocardial damage

Cardiac troponin T (cTnT) in serum is a highly sensitive and specific marker for myocardial damage. Quantitative immunoassays take 9 min. A rapid test (TropT, CardiacT) using plasma detects cTnT concentrations above 0.10 microg/l within 15 min. Both assays are specific for the cardiac isoform. In a study using the maximal values from serial sampling in 502 infarction-suspected patients, we found a diagnostic sensitivity for non-Q- and Q-wave infarctions of 100%, with a specificity of 99%. cTnT has been shown to be a powerful prognostic marker for risk stratification in acute coronary syndromes. In 30-40% of patients with unstable angina, cTnT > or = 0.10 microg/l detects minor myocardial damage (MMD) with poor prognosis. False positives may be found in certain skeletal muscle diseases, such as polymyositis and Duchennes muscular dystrophy. Constantly increased values in renal failure may be due to uremic cardiomyositis. Even in uremia, a rapid increase of cTnT will indicate acute myocardial damage. We propose a diagnostic strategy based on timed, parallel determinations of myoglobin + cTnT.

Detection of Myocardial Damage by Serial Measurements of Cardiac Troponin T, CK MBmass, and TROPT Rapid Test

Detection of cardiac damage is greatly facilitated by serial blood measurements of myocardial cell markers. In many hospitals creatine kinase MBmass concentration (CK MBmass) constitutes the biochemical criterion (WHO) for acute myocardial infarction (AMI). Cardiac troponin T (TnT) is an even more sensitive and specific marker for myocardial damage. With discriminator levels of 10.0 and 0.10μg/l, respectively, serial measurements of both markers provide a useful diagnostic strategy for ischemic heart disease. This survey reviews representative cumulated time curves in individual patients covering the spectrum of myocardial damage, including unstable angina pectoris (UAP), non and Q-wave infarctions with and without early reperfusion, re-infarction, and subacute infarction. Increased TnT detects minor myocardial damage (MMD) in over 30% of patients with UAP, although CK MBmass remains below its discriminator. Subacute infarction is detected by the wide diagnostic time window of the serum TnT at a time when CK MBmass has already returned to normal. In a substudy of 502 suspected cases of AMI, the distributions of maximum serum TnT concentrations within each patient series demonstrated that TnT had a diagnostic sensitivity of 100% and a specificity of 99%. Median, 5th and 95th percentiles of maximum TnT values within the diagnostic subgroups showed that serum TnT was increased five-fold more than CK MBmass. Median values of Q-wave AMI were higher than in non–Q-wave AMI. A diagnostic strategy using TROPT, a rapid test specific for the cardiac isoform of TnT with a detection limit 0.10μg/l, is presented.

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes

BACKGROUND International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

Analytical and clinical performance of an improved qualitative troponin T rapid test in laboratories and critical care units

OBJECTIVE To evaluate the performance of a visual troponin T rapid test in the hands of nontraditionally trained personnel of 2 critical care units in comparison to 3 laboratories. METHODS Method comparisons of the troponin T rapid test versus cardiac troponin T enzyme-linked immunosorbent assay were performed with 804 samples from 510 patients with suspected acute coronary syndromes. Cross-reactivity with skeletal troponin T was studied up to 5000 microg/L. RESULTS Laboratories and critical care units obtained comparable results in the analytical cutoff of the test (0.11 and 0. 10 microg/L) and in the diagnostic sensitivities in the detection of acute myocardial infarction (96% and 93% after 8 hours) and of high-risk patients with unstable angina pectoris (100% and 100%). Different percentages of false-positive results (0.2% and 3%) were found, which may reflect different objectives and strategies in these hospital units. The cross-reactivity with skeletal troponin T was less than 0.01%. CONCLUSIONS The troponin T rapid test gives reliable results not only when used by laboratory personnel experienced in the execution of analytical methods, but also in the hands of nurses and physicians working in clinical units outside the laboratory.