Comparison of M yoglobin, Creatine Kinase-MB, and Cardiac Troponin I for Diagnosis of Acute Myocardial Infarction*

Transcription

1 ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 26, No. 4 Copyright 1996, Institute for Clinical Science, Inc. Comparison of M yoglobin, Creatine Kinase-MB, and Cardiac Troponin I for Diagnosis of Acute Myocardial Infarction* ALAN H. B. WU, Ph.D.,t YUE JIN FENG, M.S.,t JOHN H. CONTOIS, Ph.D.,t and SHAZIB PERVAIZ, M.D., Ph.D.* tdepartment of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT and tbehring Diagnostics, Westwood, MA ABSTRACT Serial plasma concentrations of myoglobin, creatine kinase MB (CK-MB) isoenzyme, and cardiac troponin I (ctnl) were measured in 25 patients with a confirmed diagnosis of acute myocardial infarction (AMI), and 74 patients who were suspected of AMI but were subsequently ruled out for this diagnosis. The cutoff concentration for the ctnl assay was optimally determined to be 2.5 ng/ml. Of the three markers, myoglobin had the highest clinical sensitivity (50 percent) when blood was collected between 0 to 6 h after the onset of chest pain. Assays for all serum markers used had high clinical sensitivity (>93 percent) 6 to 24 h after onset. The CK-MB remained highly sensitive for 48 h, while ctnl was sensitive for up to 72 h. Between 72 and 150 h, ctnl had a clinical sensitivity of 70 percent as compared to 21 percent and 18 percent for myoglobin and CK-MB, respectively. The clinical specificity of ctnl for non-am I patients was equivalent to CK-MB and significantly higher than for myoglobin. The clinical efficiency of ctnl for all samples was better than either CK-MB or myoglobin, owing mainly to the wider diagnostic window. The specificity of ctnl for 59 patients with chronic renal failure, skeletal muscle trauma and disease was better than all of these markers including cardiac troponin T (ctnt). Results of this study show that ctnl is an effective marker for the retrospective diagnosis of AMI, and consideration should be given to its use in place of CK-MB. * Send reprint requests to: Alan H. B. Wu, Ph.D., Department of Pathology and Laboratory Medicine, Hartford Hospital, 80 Seymour Street, Hartford, CT /96/ $01.50 Institute for Clinical Science, Inc.

2 292 Introduction WU, FENG, CONTOIS, AND PERVAIZ Materials and Methods According to the World Health Organization (WHO), the diagnosis of acute myocardial infarction (AMI) is predicated on the presence of a positive clinical history including chest pain, unequivocal changes in electrocardiographic (ECG) recordings, and in creased cardiac enzyme activities in blood.1 The enzyme most frequently used for AMI diagnosis is creatine kinase-mb (CK-MB).2,3 Newer assays for other cardiac markers have been developed and are being considered as potential adjuncts or alternatives. Myoglobin becomes positive within 6 h after the onset of AMI and is considered an early marker.4 The clinical specificity of myoglobin is not as good as CK-MB because myoglobin released from skeletal muscles cannot be distinguished from that released from the heart.5 Cardiac troponins T (ctnt) and I (ctnl) are two of the three subunits of the troponin complex, a regulatory protein of the actin filament of contractile tissue.6 Assays for ctnt have showed promise in early studies in patients with acute myocardial infarction and unstable angina (UA).7 Studies using assays for ctnl have demonstrated similar performance to ctnt for the diagnosis of AMI.8,9 The specificity of ctnl may be superior to ctnt because concentrations are not increased in patients with renal failure and no documented evidence of myocardial involvement.10 The purpose of this study was to compare serum concentrations of myoglobin, CK-MB, and ctnl on patients suspected of AMI. Patients with chronic renal failure, skeletal muscle injury, and disease were also studied. All three assays were perform ed on a sin g le analyzer at the same time. The optimum decision limitfor ctnl and the clinical sensitivity, specificity, efficiency, and predictive value for a positive test were determined on all assays. S u b j e c t s Three hundred sixty-six blood samples were obtained from 102 consecutive patients admitted to Hartford Hospital (Hartford, CT) with the chief complaint of chest pain and rule-out for AMI. The diagnosis of AMI was made on 25 of these patients by attending physicians using criteria established by the WHO, including the activity of total CK and mass concentration of CK-MB. Results of myoglobin and ctnl were not made known to attending physicians at the time of diagnosis. Where known, the time of onset of chest pain was recorded for all AMI patients as documented on the medical record. The information was not available on four AMI patients, and an estimate on infarct time was made based on the clinical history and the serum concentrations of myoglobin and CK-MB. There were 76 patients on whom a diagnosis of AMI was ruled out. Of these, two suffered cardiac arrest resulting in significant myocardial injury and increased concentrations of all markers and were excluded from the study. One patient, a 78-year-old white female, had a reinfarction at approximately 72 h after the onset of chest pain. Clinical conditions associated with the AMI rule-out group included stable and unstable angina pectoris and congestive heart failure. Plasma was also obtained on 33 patients with end stage renal disease, 21 patients with skeletal muscle trauma, 4 patients with rhabdomyolysis, and one with an organophosphate (Malathion) overdose. For determination of the normal range for ctnl, 100 frozen and 50 fresh serum samples were obtained from apparently healthy individuals. Results of samples from renal and skeletal muscle patients and normal individuals were not used in the assessm ent of clinical specificity.

3 COMPARISON OF MYOGLOBIN, CK-MB, AND CARDIAC TROPONIN I FOR AMI 293 The protocol for the collection of blood samples and review of medical records was approved by the Hartford Hospital Institutional R eview Board. It was deemed that written patient consent was not necessary because blood left over from physician-ordered testing was used in all cases. Assays Blood was collected into evacuated red-top tubes (normal individuals) and green-top tubes (hospitalized patients) containing heparin and centrifuged before analysis. All samples were stored at 2 to 8 C and assayed within 48 h after collection. The manufacturer had determined that either serum or plasma specimens can be used. Total CK was assayed on an automated clinical chemistry analyzer (IL 1800).* Myoglobin and CK-MB (mass assay) were assayed using the Opus Plus Analyzer, f The upper limits of normal used for these assays were 200 U/L, 7.5 ng/ml, and 60 ng/ml for total CK, CK-MB and myoglobin, respectively.7,11 A percent relative index was also computed by dividing the total CK activity into the CK-MB concentration and multiplying by 100 (upper limit of normal: 4.0 percent).12 The ctnl was assayed on the Opus Plus Analyzer.t The upper limit for the calibration curve was 150 ng/ml. In studies conducted by the manufacturer, the ctnl assay had an analytical sensitivity of 0.5 ng/ml, determined by using both statistical calculation (mean ± 2.5 SD of the zero calibrator) and the dilutional method. The within and between run precision for ctnl was determined at three concentrations from quality control materials provided by the manufacturer. For the sub- * Instrumentation Laboratory, Lexington, MA. t Behring Diagnostics, Westwood, MA. Sensitivity FIGURE 1. Receiver operating characteristic (ROC) curve for cardiac troponin I in acute myocardial infarction. The area under the curve was 0.992, SE The optimum cutoff point was selected at 2.5 ng/ml. set of patients with chronic renal failure, skeletal muscle trauma and disease, cardiac troponin T was also assayed using the ES300.t The normal range for this assay was 0 to 0.1 ng/ml. Statistical Analysis The precision, clinical sensitivity, specificity, efficiency, positive and negative predictive values, and 95 percent confidence intervals (Cl) were calculated from standard statistical formulas.13,14 Receiver operating characteristic (ROC) curves were generated from a statistical program. Results The analysis of ctnl on healthy individuals produced results that were below t Boehringer Mannheim Diagnostics, Indianapolis, IN. Obtained through the courtesy of Charles Metz (LABROC1, University of Chicago Medical Center, Chicago, IL.

4 294 WU, FENG, CONTOIS, AND PERVAIZ the detection limit of the assay for 149 of 150 healthy individuals. One individual had a ctnl concentration of 3.1 ng/ml and may have had some silent ischemia. Based on this data, the normal range for ctnl was determined to be 0 to 0.5 ng/ml. No difference was observed between men and women or between freshly assayed and samples stored frozen at 20 C. The within-run precision for quality control materials was 10 percent at 3.9 ng/ml, 5 percent at 18.6 ng/ml, and 6 percent at 94.4 ng/ml. Corresponding between-run precision for these controls was 12 percent, 12 percent, and 9 percent, respectively. The cutoff concentration for the ctnl assay was determined by use of an ROC curve as shown in figure 1. This curve was generated from data obtained on samples collected from 6 to 72 h after onset of chest pain in AMI patients and all samples from the non-ami group. From this plot, a ctnl cutoff value of 2.5 ng/ml produced results that were closest to the ideal 100 percent clinical sensitivity and specificity values (top left corner of curve). In figure 2 are illustrated typical results of a patient who suffered an AMI. In table I are summarized the clinical sensitivity for all patients using the three assays as a function of the time of onset of chest pain. Myoglobin had the highest clinical sensitivity during the earliest interval of 0 to 6 h after the onset of chest pain, followed by CK-MB. The ctnl was not useful as an early marker of AMI (clinical sensitivity 25 percent). During the 6 to 12 h interval, CK-MB appeared to have the highest clinical sensitivity; however, because of the small number of patients in this group, results were not significantly different from either myoglobin or ctnl. The clinical sensitivity of myoglobin began to drop beginning at 12 h after onset, and by 24 h the sensitivity was too low for it to be a useful diagnostic test. Similarly, the clinical sensitivity of CK-MB declined at 48 hours. The clinical sensitivity at the 72 to 150 h interval for myoglobin and CK-MB of 24 percent and 18 percent, respectively, was partly the result of one patient who suffered a reinfarction during the hospitalization period. Excluding this patient from the F i g u r e 2. T y p i c a l r e s u l t s o f m y o g l o b i n, C K -M B a n d tr o p o n in I in a p a tie n t w ith a c u te m y o c a r d ia l in f a r c tio n (A M I). ( T h is p a r t i c u l a r p a t i e n t w a s s e le c te d b e c a u s e card i a c m a r k e r s w e r e o r d e r e d b e y o n d h o u r s a f t e r c h e s t p a i n o n s e t, w h i c h t o d a y, is s o m e w h a t u n u s u a l i n u n c o m p l i c a t e d A M I c a s e s.) Time after onset (hours)

5 COMPARISON OF MYOGLOBIN, CK-MB, AND CARDIAC TROPONIN I FOR AMI TABLE I Clinical Sensitivity and Specificity for Cardiac Markers of Acute Myocardial Infarction* Time Interval, Hr Myoglobin Creatine Kinase-MB Cardiac Troponin 1 Sensitivity /20,50% 8/20, 40% 5/20, 25% 28-72% 19-62% 6-44% /14, 93% 14/14,100% 13/14, 93% % 100% % /27, 63% 27/27,100% 27/27, 100% 45-81% 100% 100% /33, 39% 30/33,91% 33/33, 100% 22-59% % 100% /21, 10% 9/21,43% 20/21, 95% 0-23% 22-64% % /33, 24% 6/33, 18% 23/33, 70% 9-39% 5-31% 54-86% Specificity 179/218, 82% 215/218, 99% 209/218, 96% 77-87% % 93-99% Efficiency 242/366, 66% 309/366, 84% 330/366,90% 61-71% 80-88% 87-93% Predictive value, 63/101, 62% 94/97, 97% 121/134, 90% positive 54-73% % 85-95% Predictive value, 179/265, 68% 215/269, 80% 209/232, 90% negative 62-74% 75-85% 85-93% *95 percent confidence interval given under each result. analysis reduced the clinical sensitivity for myoglobin and CK-MB to 11 percent and 4 percent, respectively. In contrast, ctnl, had a clinical sensitivity of 100 percent from 12 to 72 hours and continued to have a 70 percent clinical sensitivity from 72 to 150 hours (table I). The ctnl exhibited a prolonged release from damaged myocytes because of the time necessary to degrade the contractile apparatus. Positive results were observed for up to 1 week after AMI. The ctnl had the widest detection window of the three markers studied for retrospective diagnosis of AMI. For detection of reinfarction at >72 h after the initial AMI, myoglobin and CK-MB were superior to ctnl, as the values had returned to normal by this time. The clinical specificity was evaluated on 74 patients without evidence of AMI. Results showed that the difference between CK-MB and ctnl were not statistically significant (as shown in table I).

6 296 WU, FENG, CONTOIS, AND PERVAIZ Two patients accounted for most of the false positive values for ctnl observed in this study. The efficiency of ctnl for diagnosis of AMI was slightly higher than for CK-MB (90 percent vs. 84 percent) although results were not significantly different. The predictive values (PV) were also similar: CK-MB was slightly better for positive PV and ctnt was better for negative PV. Both tests were significantly better than myoglobin for efficiency and predictive values. In figure 3 are shown the results of cardiac markers for patients with renal failure and skeletal muscle trauma. Of the chronic renal failure group, total CK (overall range 10 to 1910 U/L) and CK-MB (range 0.6 to 16.4 ng/ml) were increased in 2 of 33 (6 percent) cases. The relative CK-MB index was abnormal in one of these two patients. Myoglobin was increased in 29 (88 percent) of these patients (range: 44 to 6540 ng/ml), ctnt was increased in 19 (57 percent) (range: 0 to 6.0 ng/ml). The ctnl was increased in 4 of these patients with high ctnt (12 percent, range 0 to 13.6 ng/ml). One patient had open heart surgery a week prior to testing; another had new onset of myocardial ischemia with positive results for CK-MB (and percent relative index); the third had documented cardiomyopathy; and the fourth had elective surgery for repair of an aortic aneurysm (blood sampled 3 days after surgery). In 21 patients with skeletal muscle trauma, total CK was increased in 15 (71 percent) (range: 140 to 3032 ng/ml), myoglobin in 18 (86 percent) (range: 10 to 1900 ng/ml), and CK-MB in 3 (range: <1.0 to 19.3 ng/ml). The relative CK-MB index was normal for all trauma patients, indicating that the source of this isoenzyme was from skeletal muscle. Both ctnt and ctnl were normal in all of these cases. Results of serial samples from four patients with rhabdomyolysis (case #1 to 4) and one patient with an organophosphate intoxication (#5) are shown in table II. Samples from cases #1 and #2 were grossly increased for myoglobin, total CK and CK-MB. The ctnt was increased in all five patients, while ctnl was increased in only one. Echocardiography of the one positive ctnl case dem- &^ 100-n B. 50- F i g u r e 3. R e l a t i v e in c r e a s e s o f c a rd ia c m a rk - e r s i n p a t i e n t s w i t h c h r o n ic r e n a l d is e a s e a n d s k e le ta l m u s c le tr a u m a. R e s u lts a re e x p r e s s e d in m u l t i p l e s o f t h e u p p e r r e f e r e n c e lim it...a : TCK CK-MB Myo ctnt ctnl Chronic Renal Failure TCK CK-MB Myo ctnt ctnl Skeletal Muscle Trauma

7 COMPARISON O F MYOGLOBIN, CK-MB, AND CARDIAC TROPONIN I FOR AMI 297 TABLE II Results of Serial Samples from Patients with Rhabdomyolysis and Malathion Overdose Time After Admission, Hr Total CK U/L CK-MB ng/ml Relative Index, % Myoglobin ng/ml ctnt ng/ml ctnl ng/ml Case # < , , , Case # , , , , , , , Case # Case # < <0.5 Case # < < < < 1.0 < < 0.5 CK = creatine kinase. CK-MB = creatine kinase MB. ctnt = cardiac troponin T. ctnl = cardiac troponin I. onstrated mild left ventricular dilatation, global left ventricular hypokinesis, and akinetic septum. The ejection fraction was 40 percent (normal 50 to 70 percent). Discussion Analysis of serum on individuals presumed to be healthy produced a reference range of 0 to 0.5 ng/ml for the ctnl assay described in this study. The cutoff concentration refers to the value that is optimal for a specific diagnosis. In the case of AMI, cutoff values are always higher than the upper limit of normal. Indeed, a patient may have an abnormally high ctnl value that is not indicative of this disease. When comparing results of different biochemical markers for AMI, such as shown in figure 2, increases relative to the cutoff limit values are often used (e.g., multiples of 2.5 ng/ml for ctnl). The actual cutoff value used for determination of AMI has a direct influence on the clinical sensitivity and specificity of the assay. In this study, ROC curves were used to determine the optimal cutoff concentration.

8 298 WU, FENG, CONTOIS, AND PERVAIZ Because cardiology practices differ from one institution to another, it is the responsibility of the clinical laboratory (in conjunction with cardiology) and not the manufacturer to establish the most appropriate decision limit or cutoff concentration. The ctnl cutoff concentration of 2.5 ng/ml reported here for diagnosis of AMI is near the value of 3.1 ng/ml reported for the Stratus* ctnl assay,15 and the value of 2.1 ng/ml reported for an experimental ctnl assay.10 In contrast, the cutoff concentration for the Access! assay is 0.1 ng/ml,16 similar to that of troponin T. This points out the need for the creation of an accepted standard material for troponin I, similar to one being proposed for CK-MB.17 This standard would be used to calibrate all ctnl assays so that equivalent results can be obtained. Our results demonstrate that myoglobin is better than either CK-MB and ctnl for early diagnosis of AMI, i.e., during the 0 to 6 h window. This is in contrast to the findings of Mair et al. who showed that myoglobin and CK isoforms were equivalent to assays of ctnt, ctnl, myoglobin, and mass assays of CK-MB.18 In their studies, a immunoturbidimetric assay was used for myoglobin that had an analytical sensitivity of 50 ng/ml and a cutoff of 70 ng/ml. The Opus Plust- fluorometric immunoassay used for myoglobin in this report had a higher analytical sensitivity of 1.0 ng/ml11 which may enable earlier detection of AML After 6 h, ctnl had high clinical sensitivity and an extended diagnostic window. This finding is consistent with previous reports for both troponin I8,9 and T.7,18 The specificity of ctnl is equivalent to CK-MB in non-ami patients with documented cardiac disease. Patients who have minor myocardial injury will produce false positive results for the diagnosis of AMI using sensitive cardiac markers, because the degree of injury may not be enough for it to be classified by attending p h ysicians as AMI. The im proved sp ecificity of ct nl over CK-MB is demonstrated in patients with skeletal muscle injury whereby high concentrations of CK-MB were observed in the absence of cardiac injury. In four patients who were positive for CK-MB, ctnl was negative suggesting that abnormal MB concentrations originated from skeletal muscle. In patients with renal failure, total CK and CK-MB were normal in the majority of cases. In contrast, myoglobin was increased in most samples. This finding is not unexpected since myoglobin is a small protein normally cleared by the kidneys, but retained in the circulation of renal failure patients.11 The finding of a substantial number of patients with increased ctnt concentrations is also consistent with other studies.10,19 At this time, it is not clear if high troponin T concentrations seen in these patients is due to re-expression of troponin T in regenerating skeletal muscles (as observed by Bodor et al. in patients with Duchenne Muscular Dystrophy), non-specificity of the existing ctnt assay, or a true indication of minor myocardial injury.21 In the four ctnt positive patients who were also positive for ctnl, a cardiac source was implicated by review of medical records. If one assumes that ctntpositive patients do not have silent myocardial ischemia, it would appear that the ctnl assay may be more accurate than ctnt in d etectin g minor myocardial injury. In patients with skeletal muscle injury, total CK and myoglobin were abnormal * Dade International, Miami, FL Sanofi Diagnostics Pasteur, Chaska, MN. ES 300, Boehringer Mannheim Diagnostics, t Instrumentation Laboratory, Lexington, MA. Indianapolis, IN.

9 COMPARISON OF MYOGLOBIN, CK-MB, AND CARDIAC TROPONIN I FOR AMI 299 in the majority of cases, as expected; CK-MB was positive in only three. There were no false positive increases in ctnt or ctnl in these patients. The ctnt was increased in all four patients with rhabdomyolysis, however, while ctnl was increased in only one. Review of the chart suggested the possibility of myocardial injury in this one case with positive ctnl results. The success of ctnt for risk stratification in AMI rule-out patients suggests that investigations are warranted for ctnl. A meta-analysis combining several risk assessm ent studies showed that unstable angina (UA) patients who have abnormal concentrations of ctnt have a 4-fold higher odds ratio for cardiac death or a nonfatal AMI than UA patients who have normal values.22 The similarity of ctnl and ctnt release into blood after AMI suggest that ctnl may also have prognostic value. Moreover, ctnl is increased in a subset of patients with unstable angina.23,24 Whether or not this indicates a poor cardiac prognosis remains to be determined. Summary This study shows that of the three cardiac markers tested, myoglobin had the highest sensitivity during the initial hours after AMI. However, the specificity of myoglobin is not as good as either CK-MB or ctnl; therefore, this test is most useful for AMI rule-out. Newer markers such as glycogen phosphylase BB and fatty acid binding protein are being examined to determine if a higher degree of clinical specificity can be achieved.25,26 For the retrospective diagnosis of AMI (i.e., 3=12 h), ctnt has a wider diagnostic window and has a higher clinical specificity for AMI diagnosis than either CK-MB or myoglobin. The ctnl assay also appears to be more specific than ctnt for ruling out AMI in patients with chronic renal failure and acute rhabdomyolysis. Therefore, when more FDA approved, affordable, and convenient random-access assays for ctnl become available, it may be the test of choice for the retrospective diagnosis of AMI and rule out. Acknowledgments The authors acknowledge Behring Diagnostics for equipment, reagents, and financial support for conducting this study. References 1. World Health Organization. Report of the Joint International Society and Federation of Cardiology/World Health Organization Task Force on Standardization of Clinical Nomenclature. Nomenclature and criteria for diagnosis of ischemic heart disease. Circulation 1979;59: Lee TH, Weisbert MC, Cook F, et al. Evaluation of creatine kinase and creatine kinase-mb for diagnosing myocardial infarction. Arch Intern. Med 1987;147: Wu AHB, Gornet TG, Bretaudiere JP, Panfili PR. Comparison of enzyme immunoassay and immunoinhibition for creatine kinase MB in diagnosis of acute myocardial infarction. Clin Chem 1985;31: Gibler WB, Gibler CD, Weinshenker E, et al. Myoglobin as an early indicator of acute myocardial infarction. Ann Emerg Med 1987; 16: Mair J, Artner-Dworzak E, Lechleitner P, et al. Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin. Br Heart J 1992;68: Katus HA, Scheffold T, Remppis A, Zehlein J. Proteins of the troponin complex. Lab Med 1992;23: Wu AHB, Valdes R Jr, Apple FS, et al. Cardiac troponin-t immunoassay for diagnosis of acute myocardial infarction and detection of minor myocardial injury. Clin Chem 1994;40: Bodor GS, Porter S, Landt Y, Ladenson JH. Development of monoclonal antibodies for an assay of cardiac troponin-i and prelim inary results in suspected cases of myocardial infarction. Clin Chem 1992;38: Larue C, Calzolari C, Bertinchant JP, et al. Cardiac-specific immunoenzymometric assay of troponin I in the early phase of acute myocardial infarction. Clin Chem 1993;39: Hafner G, Thome-Kromer B, Schaube J, et al. Cardiac troponins in serum in chronic renal failure. Clin Chem 1994;40: Wu AHB, Laios I, Green S, et al. Immunoassays for serum and urine myoglobin: myoglobin

10 3 00 WU, FENG, CONTOIS, AND PERVAIZ clearance assessed as a risk factor for acute renal failure. Clin Chem 1994;40: El Allaf M, Chappelle JP, Allaf DE, et al. Differentiating muscle damage from myocardial injury by means of the serum creatine kinase (CK) isoenzyme MB mass measurement/total CK activity ratio. Clin Chem 1986;32: Galen RS, Gambino SR. Beyond normality. The predictive value and efficiency of medical diagnoses. New York: Wiley, Gardner MJ, Altman DG. Statistics with confidence. C onfidence intervals and statistical guidelines. London: British Medical Journal, Adams JE, Bodor GS, Davaila-Roman VG, et al. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation 1993;88: Mair J, Morandell D, Genser N, et al. Equivalent early sensitivities of myoglobin, creatine kinase MB mass, creatine kinase isoform ratios, and cardiac troponins I and T for acute myocardial infarction. Clin Chem 1995;41: Green S, Onoroski M, Moore R, et al. Standardization of CK-MB mass immunoassays [Abstract]. Clin Chem 1994; Katus HA, Remppis A, Neumann FJ, et al. Diagnostic efficiency of troponin T measurements in acute m yocardial infarction. Circulation : Li D Keffer J, Corry K, Vazquez M, Jialal I. Nonspecific elevation of troponin T levels in patients with chronic renal failure [Abstract]. Clin Chem 1995;41:S Bodor GS, Porterfield D, Voss E, et al. Cardiac troponin-t composition in normal and regenerating human skeletal muscle [Abstract]. Clin Chem 1995;41:S Katus HA, Haller C, Muller-Bardorff M, et al. Cardiac troponin T in end-stage renal disease patients undergoing chronic m aintenance hemodialysis. Clin Chem 1995;41: Wu AHB, Lane PJ. Meta-analysis in clinical chemistry: validation of cardiac troponin T as a marker for ischemic heart diseases. Clin Chem 1995;41: Cummins B, Auckland MC, Cummins P. Cardiac-specific troponin I radioimmunoassay in the diagnosis of acute myocardial infarction. Am Heart J 1987;113: Hirayama A, Nishida K, Naito J, et al. Clinical assessment of a rapid sensitive enzyme immunoassay specific for human cardiac troponin I. J Am Coll Cardiol 1991;17:330A. 25. Rabitzsch G, Mair J, Lechleitner P, et al. Immunoenzym om etric assay of hum an glycogen phosphorylase isoenzyme BB in diagnosis of ischemic myocardial injury. Clin Chem 1995; 41: Tsuji R, Tanaka T, Sohmlya K, et al. Human heart-type cytoplasmic fatty acid-binding protein in serum and urine during hyperacute myocardial infarction. Int J cardiol 1993;41: