Current Issue
FEBRUARY 1999 - VOLUME 19 - NUMBER 1
Marguerite J. Murphy and Christine B. Berding
About the Authors
Marguerite J. Murphy, RN, MSN is an assistant professor in adult nursing at the Medical College of Georgia, Barnesville. Christine B. Berding, RN, MSN, CCRN is an instructor in adult nursing at the Medical College of Georgia, Athens. Both Murphy and Berding have 14 years of clinical experience in critical care and teach in the School of Nursing, with classroom and clinical teaching responsibilities related to critical care nursing.
This article originally appeared in the February 1999 issue of Critical Care Nurse, Vol 19, No. 1, pp 58-66. Reprint requests: InnoVision Communications, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or (949) 362-2050 (ext 515); fax, (949) 362-2022; e-mail, ivcReprint@aol.com.
The nursing care of patients with acute myocardial ischemia has evolved in recent years as new monitoring techniques and treatment methods have been developed. Healthcare providers now aggressively pursue an accurate diagnosis of an acute myocardial infarction (AMI) during the first few hours after the onset of signs and symptoms so that viable cardiac muscle can be salvaged through early thrombolytic therapy or interventional procedures such as angioplasty or atherectomy. A rapid, accurate diagnosis of chest pain facilitates routing of patients to the appropriate unit or setting for monitoring and treatment.
Current trends in healthcare finances have also had a tremendous effect on the delivery of care to patients with AMI. Timely, accurate diagnosis of AMI affects the financial aspect of patients’ care in 2 ways. First, the cost to healthcare agencies is significant each time a patient is admitted with chest pain and an AMI is eventually ruled out. Second, discharge of patients from the emergency department with a missed diagnosis of AMI is a major source of legal action,1,2 contributing to the financial liability of healthcare agencies. The combination of these factors has influenced the ongoing search for diagnostic measures that promote the prompt and accurate diagnosis of myocardial ischemia.
Diagnostic indicators of AMI must be specific and sensitive. Specificity refers to how often a diagnostic test provides false-positive results. The specificity indicates the degree that a test is influenced by factors other than the factor being evaluated. For example, a test that is 100% specific for cardiac ischemia would be influenced only by the presence of myocardial ischemia. No test results would be false-positive. Sensitivity refers to how often a test provides false-negative results. The sensitivity indicates the degree that the diagnostic test is influenced by the factor being measured. For example, a test that is 100% sensitive for the diagnosis of AMI would always indicate the presence of myocardial ischemia, no matter how slight the ischemia. No results would be false-negative.
Therefore, the ideal diagnostic test for AMI would be a specific and sensitive indicator of myocardial cell damage within the first few hours after the ischemic event. Although no diagnostic test that totally meets these criteria is currently available, recent findings indicate that assays for some biochemical markers—serum myoglobin, cardiac troponin T, and cardiac troponin I—may make important contributions in this area.
Review of Current Diagnostic Practice
Currently, healthcare providers use the criteria established by the World Health Organization (WHO) to diagnose AMI. At least 2 of the 3 following criteria must be met for AMI to be diagnosed: (1) ST-segment changes or new Q waves must be present on the patient’s electrocardiogram (ECG), (2) the patient must have reported chest pain characteristic of AMI, and (3) the patient must have abnormally elevated serum levels of cardiac enzymes such as creatine kinase MB (CK-MB).3 Although these criteria have become the reference standard for the diagnosis of AMI, some problems exist. As many as 24% to 60% of patients with AMI do not have ECG changes indicative of AMI on admission,1 and one third of patients with AMI do not have the typical clinical findings of chest pain associated with an AMI.3,4
Healthcare practitioners often rely on the elevation of CK-MB levels as the definitive diagnostic finding when a patient has nonspecific ECG changes or atypical signs and symptoms. However, CK-MB levels do not increase until 4 to 8 hours after the ischemic event, and they return to normal within 48 to 72 hours,5 creating a somewhat limited window of opportunity for diagnostic use. CK-MB levels can also be affected by other diseases or injuries, especially diseases that affect the skeletal muscles.4,6 These limitations of the WHO criteria can have an adverse effect on the prompt, accurate diagnosis of an AMI.
The American College of Cardiology (ACC) and the American Heart Association (AHA) recognize the use of the WHO criteria for the diagnosis of AMI but note that in some situations the WHO criteria are inadequate for providing an accurate diagnosis of AMI. The ACC and AHA guidelines for the management of AMI suggest that measurements of serum levels of myoglobin and cardiac troponins T and I may be useful supplements to measurements of CK-MB levels in the diagnosis of AMI.7
Myoglobin
Myoglobin is a heme protein that is found in all striated muscle fibers, which account for about 2% of both skeletal and cardiac tissue mass. The small molecular weight of myoglobin8 allows it to be rapidly released from muscle tissue when the tissue is damaged. This release of myoglobin is particularly important when one is trying to determine if cardiac muscle has been damaged. Molecules of creatine kinase and its isoform CK-MB are larger than those of myoglobin7 and are released more slowly after an AMI. Because myoglobin escapes rapidly from damaged myocardial cells, it can be detected as soon as 2 hours after an AMI, with peak serum levels occurring in 3 to 15 hours (see Figure).
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An elevated myoglobin level has been detected in more than two thirds of patients with AMI at 3 hours and in nearly all patients by 6 hours after the onset of chest pain.10 In a study11 of 89 patients with suspected AMI, measurement of myoglobin levels in blood samples obtained 2 hours after the patient came to the emergency department with chest pain had a sensitivity of 100% for detecting AMI. If the myoglobin level does not increase within the first 3 to 6 hours after the onset of chest discomfort, an AMI has not occurred.10
Although using early detection of elevated myoglobin levels in patients with chest pain to determine whether an AMI has occurred sounds ideal, some disadvantages are apparent. Because both cardiac and skeletal muscle contain myoglobin, many non–cardiac-related factors, such as skeletal muscle or neuromuscular disorders, strenuous exercise, renal failure, intramuscular injections, and cardiac bypass surgery, can elevate serum levels of the protein.8 Heavy use of ethanol can also elevate serum myoglobin levels.12 Myoglobin levels remain unchanged with light exercise.13 Cardiac catheterizations that are not associated with AMI do not affect the myoglobin level13; however, controversy exists about whether congestive heart failure not associated with AMI increases serum myoglobin levels.12,13
Additional factors such as race, sex, and age may also affect normal myoglobin levels. Myoglobin levels increase with age and are higher in African American men than in white men. Some discussion has centered on whether myoglobin levels differ in men and women. Results of some studies indicate higher myoglobin levels in men, whereas other studies suggest that myoglobin levels do not differ significantly between men and women.8 Finally, controversy also exists about the level at which myoglobin becomes indicative of an AMI, with the reported reference ranges varying from 50 to 120 µg/mL.8,11 Because of these variables, the sensitivity and specificity of myoglobin tests vary, depending on the criteria defined for diagnosis of AMI.
The specificity of myoglobin tests in the diagnosis of AMI can be increased by monitoring an additional marker, carbonic anhydrase III (CA-III). CA-III is found primarily in skeletal muscle and occurs in trace amounts in the myocardium. Because damage to skeletal muscle results in the release of both myoglobin and CA-III, and damage to cardiac tissue results primarily in release of myoglobin, the ratio of myoglobin to CA-III can be used to determine if infarction has occurred.14 The normal range for CA-III is 13 to 29 µg/L. A serum myoglobin concentration greater than 110 µg/L together with a myoglobin/CA-III ratio of 3.21 or higher is considered abnormal or indicative of AMI.15
Although myoglobin is not the perfect cardiac marker for diagnosing AMI, it is the earliest significant indicator of breakdown of myocardial cells.8 Myoglobin may be most helpful when used in conjunction with other cardiac markers in the rapid determination of AMI, especially in patients with atypical chest pain or nonspecific ECG changes.
Cardiac Troponins
The cardiac troponin complex is a basic component of the myocardium. Through its role in the transmission of intracellular calcium into the actin-myosin interaction, the troponin complex is involved in the contraction of the myocardial muscle. The complex is composed of 3 proteins: cardiac troponin T, cardiac troponin I, and cardiac troponin C. This same troponin complex is found in skeletal muscle.16 However, the structures (amino acids) of troponins T and I found in cardiac muscle differ from the structures of troponins T and I found in skeletal muscle, and these differences can be used to distinguish the 2 types (cardiac vs skeletal). The structures of cardiac and skeletal troponin C are identical, so cardiac troponin C is not useful as a cardiac marker.1
When myocardial ischemia occurs, the cell membranes become more permeable, and intracellular components such as the cardiac troponins leak into the interstitium and into the intravascular space. These proteins have a relatively small molecular size, so their transport across the injured cell membrane occurs soon after the injury occurs.17 Cardiac troponins T and I are not found in significant levels in the blood of healthy adults, so the presence of those troponins in the serum is an indication of the death of myocardial tissue.9,18 The serum level of cardiac troponin T begins to increase 3 to 5 hours after myocardial injury occurs and remains elevated for 14 to 21 days.9,17,18 Cardiac troponin I levels begin to increase 3 hours after myocardial ischemia occurs,19 peak at 14 to 18 hours, and remain elevated for 5 to 7 days9 (see Figure).
The sensitivity and specificity of assays for cardiac troponins T and I have been studied extensively. Assays for cardiac troponin T have a sensitivity of up to 100% for myocardial damage within 4 to 6 hours after an AMI,9 and assays for cardiac troponin I have a sensitivity of up to 100% by 6 hours after an AMI.9 No standardized reference values are available for cardiac troponins T and I because of differences in equipment, institutional policies, and professional interpretation of research findings. The lack of standardized upper reference levels for the troponins may account in part for variations in the sensitivity and specificity reported for tests for these markers in the diagnosis of AMI.
The upper reference levels generally accepted as indicative of AMI are a serum level of cardiac troponin T of at least 0.1 to 0.2 µg/L9,20 or a serum level of cardiac troponin I of at least 1.5 to 3.1 µg/L.21,22 Another factor that contributes to the discrepancy in standardized reference levels is that several forms and subunits of cardiac troponins T and I are found in the blood after AMI. For example, a small percentage of the cardiac troponins (6-8% of cardiac troponin T and 3-4% of cardiac troponin I) is found in the cytoplasm; the rest is structurally bound. The cytoplasmic troponin is released during the initial stages of AMI, and structurally bound cardiac troponin is released as myocardial necrosis continues.23 The released cardiac troponins have been measured in the serum as free units (eg, cardiac troponin T or cardiac troponin I) or as part of a complex unit, which is a unit that has troponin proteins bound to each other (eg, cardiac troponin T-C, cardiac troponin T-I). The presence of both free and complex troponin units has led to discussion of the need for standardization of cardiac troponin assays.24
Detection of cardiac troponin I in serum is very specific for myocardial injury because this protein is found only in myocardial cells.6,25 The serum level of cardiac troponin I is not influenced by skeletal muscle disease, trauma to skeletal muscle,20 or chronic renal failure,6 as are the other cardiac markers. This specificity makes measurement of cardiac troponin I a particularly useful diagnostic tool in patients with complex physical problems.20
The specificity of tests for cardiac troponin T in the diagnosis of AMI is high; however, 2 factors can decrease the specificity in certain groups of patients. First, some studies have shown that cardiac troponin T is released from the myocardial cells in unstable angina.3 Although this finding diminishes the specificity of cardiac troponin T tests for AMI, it increases the prognostic usefulness of measurements of cardiac troponin T in patients with ischemic heart disease.1,4
Second, the gene for cardiac troponin T is found in skeletal muscle during fetal development. During periods of prolonged skeletal muscle injury and regeneration, skeletal muscles appear to “revert back to the fetal state” and release cardiac troponin T, thus increasing serum levels of cardiac troponin T.4 Elevated serum levels of cardiac troponin T have also been found in patients with chronic renal failure, possibly because of skeletal muscle myopathy associated with chronic renal failure.26 Therefore, patients with chronic renal disease26 or an acute muscle disease such as rhabdomyolysis or trauma8 may have elevated serum levels of cardiac troponin T without myocardial damage, generating a false-positive test result.
Serum levels of cardiac troponins may also be used as noninvasive indicators of the effectiveness of reperfusion therapy after AMI. Levels of cardiac troponin T can indicate the success of reperfusion as early as 90 minutes after thrombolytic therapy has been started.8,27 An early, sharp increase in the serum level of cardiac troponin T results from the “washout” of cytoplasmic cardiac troponin T after reperfusion occurs. Because myocardial damage is limited by reperfusion, the amount of structurally bound cardiac troponin T released will be decreased. Reperfusion can be assessed by monitoring and calculating these changes in the levels of cardiac troponin T.23 Cardiac troponin I has also shown promise as a clinical indicator of reperfusion.19
Comparison of Myoglobin and the Cardiac Troponins With CK-MB
Myoglobin
In an attempt to find a specific and sensitive biochemical marker to use as an early indicator of AMI, many researchers have compared myoglobin with CK-MB. In a small study11 (n = 25), 52% of patients with AMI had elevated serum levels of myoglobin before an increase in CK-MB level occurred. In another study,15 within 3 hours after the onset of chest pain, measurements of myoglobin were as specific as and significantly more sensitive than measurements of CK-MB in the diagnosis of AMI.
The use of serial measurements of myoglobin levels to detect AMI may improve the diagnostic efficacy of myoglobin as a marker in the early detection of AMI. When myoglobin levels are measured at 2-hour intervals from the onset of chest pain, the sensitivity and specificity of myoglobin assays increase significantly. A doubling of myoglobin levels from one blood sample to the next sample obtained 2 hours later is indicative of AMI.6 The sensitivity of myoglobin tests increased from 50% to 60% for the blood sample obtained when the patient arrived in the emergency department after the onset of chest pain, to 100% for the second blood sample obtained 2 hours later.11,28,29 Specificity can increase to 98% after 2 consecutive blood samples obtained 2 hours apart.11,30
Cardiac Troponin T
Assays for cardiac troponin T have a sensitivity similar to that of assays for CK-MB in diagnosing AMI during the first 3 hours after the onset of chest pain; the sensitivity of CK-MB tests increases during the 3- to 6-hour period after the onset of pain.31 Another study19 showed that CK-MB tests are more sensitive than cardiac troponin T tests within 0 to 4 hours after AMI. Both cardiac troponin T and CK-MB levels are affected by skeletal muscle injury and regeneration.
Thus, measurements of these markers must be used carefully for accurate diagnosis of AMI in patients who have experienced trauma, surgery, or other diseases that involve muscle degeneration and regeneration. The presence of cardiac troponin T is a superior prognostic indicator for patients with unstable angina. A strong, direct correlation has been shown between cardiac troponin T levels and the risk of complications or death associated with unstable angina during the 30-day32 and 6-month33 periods after an elevated level of cardiac troponin T is detected.
Cardiac Troponin I
Many studies have shown that the specificity of assays of cardiac troponin I is much greater than the specificity of assays of CK-MB. Cardiac troponin I tests are more specific than and as sensitive as CK-MB tests in the diagnosis of AMI in 7 to 14 hours after the onset of chest pain.27,34 However, one study19 showed that CK-MB tests were more sensitive than cardiac troponin I tests during the first 4 hours after AMI. Because of the increased CK levels associated with the muscle damage inherent in almost all surgeries, cardiac troponin I tests are more specific than CK-MB tests in the diagnosis of perioperative AMI.35
In several studies36,37 done to evaluate the effect of cardioversion on levels of CK-MB and cardiac troponin I, the CK-MB levels were elevated after cardioversion, but the cardiac troponin I levels were unaffected. The presence of cardiac troponin I has a stronger prognostic value than does the presence of CK-MB for determining short-term mortality in patients with unstable angina. In one large study18 (n = 1404), a strong, direct relationship was found between serum levels of cardiac troponin I of at least 0.4 µg/L and an increased mortality rate during the 42 days of the study. The use of measurements of cardiac troponin I as a prognostic indicator for patients with unstable angina is further supported by results of a study38 in which the frequency of AMI and death in patients with an elevated cardiac troponin I level was evaluated. Patients with a serum level of cardiac troponin I of at least 3.1 µg/L were more likely to experience an AMI or to die during a 30-day and a 1-year period after the detection of the elevated cardiac troponin I level.38
Implications for Nursing Practice
Nurses must be familiar with the advantages and limitations of the tests used to diagnose AMI. Nurses should be aware of the time that has elapsed since the onset of the patient’s chest pain so that the appropriate diagnostic tests can be reviewed in a timely manner. The CK-MB level seems to be the most specific and sensitive indicator of AMI during the first 4 hours after the onset of chest pain.19 Elevated serum myoglobin levels are also indicative of AMI during this period, but because of the low specificity of myoglobin tests, AMI should be confirmed by measuring levels of CK-MB, cardiac troponin T, or cardiac troponin I.
Although elevated myoglobin levels can indicate the presence of AMI, an AMI can be ruled out if the myoglobin level is not elevated within 3 to 6 hours after the onset of chest pain.10 Nurses should remember that the sensitivity of assays for serum myoglobin for diagnosis of AMI declines 12 to 24 hours after the ischemic event33 and that CK-MB is not a sensitive indicator beyond 48 hours after an AMI.34 Cardiac troponin T becomes a sensitive indicator of AMI by 4 to 6 hours after the onset of chest pain.9
Cardiac troponin I becomes a sensitive indicator of AMI by 6 hours after the onset of chest pain.9 The cardiac troponins provide a longer diagnostic window, because they remain sensitive indicators of AMI for up to 7 days.19,34 Therefore, if a patient presents with chest pain that occurred more than 48 hours earlier, the cardiac troponins may be the superior diagnostic indicators of AMI. The prolonged elevation of serum levels of cardiac troponins may mask the diagnosis of any reinfarction that occurs during this 7-day period. CK-MB may be the best indicator of a reinfarction that occurs 48 hours to 7 days after the initial chest pain.34 Some evidence suggests that the occurrence of a second peak in the cardiac troponin T level can be used as an indicator of reinfarction.23
Nurses caring for a patient with suspected AMI must be aware of the patient’s complete clinical picture so that factors other than myocardial ischemia that influence the biochemical markers can be recognized. This awareness facilitates the appropriate selection and accurate interpretation of the diagnostic tests. For example, myoglobin and CK-MB levels may not accurately reflect the occurrence of AMI during the intraoperative and postoperative periods because of the muscle damage incurred with most surgical procedures. Therefore, the cardiac troponins are the superior chemical indicators of an AMI that occurs during the intraoperative or postoperative period.
Cardiac troponin I is the only biomarker that is 100% specific for myocardial necrosis and may be the most appropriate biochemical indicator of AMI in patients with complex clinical problems. Cardiac troponin I is probably the best biochemical indicator of AMI in patients with chronic renal failure and regenerative muscular disorders such as rhabdomyolysis or muscular dystrophy, because these factors can elevate levels of cardiac troponin T, myoglobin, and CK-MB. Levels of cardiac troponins T and I may be elevated in unstable angina that is not associated with AMI. Although this possibility decreases the sensitivity of assays of cardiac troponins in the diagnosis of AMI, nurses should recognize that patients with elevated levels of cardiac troponins T and I should be monitored carefully because these patients have experienced some degree of myocardial injury, a situation that places the patients at a greater risk of complications or death.24
Rapid bedside assays are available to provide measurements of levels of cardiac troponins T and I within 20 minutes.39 In some settings, nurses may be responsible for obtaining the blood samples and performing these tests. Reliable test results can be obtained when nurses perform the rapid bedside test to measure the level of cardiac troponin T.39 In order to ensure accurate test results, nurses should receive adequate education about the procedure before the institution of a policy of having nurses perform the bedside assays. The bedside assays provide qualitative results, indicating only a positive or negative test result. In a recent study,40 the reliability of the bedside assays was confirmed by comparing the qualitative results of the assays with quantitative controls.
Studies have indicated that cardiac troponin levels can be used as indicators of the size of a myocardial infarct, to predict the prognosis of patients with unstable angina, and as noninvasive indicators of coronary artery reperfusion after interventional therapies. As these uses of cardiac troponins T and I become more widely accepted, nurses have a responsibility to review the literature to become familiar with advantages and limitations in the use of these tests.
Measurements of myoglobin and cardiac troponins can be important components in the evaluation of ischemic heart disease. Assays of these markers should be used in conjunction with electrocardiography, echocardiography, stress tests, radionuclide studies, coronary angio-graphy, and assays of CK-MB levels to provide the most complete diagnostic information for AMI.
Summary
Research indicates that no tests of a single cardiac marker are 100% specific and sensitive for diagnosis of AMI in all patients. Each biomarker has advantages and disadvantages (see Table). Overreliance on a single diagnostic test is risky. Specific tests should be ordered on the basis of the individual patient’s assessment and medical history. Nurses are an important link in the collection of patients’ medical history and in assessment as well as in the interpretation of patients’ laboratory results. A knowledge of diagnostic tests commonly used in the care of patients with ischemic heart disease is imperative if patients are to receive appropriate, timely, cost-effective care.
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References
1. Alonsozana GL, Christenson RH. The case for cardiac troponin T: marker for effective risk stratification of patients with acute cardiac ischemia. Clin Chem. 1996;42:803-808.
2. Karcz A, Holbrook J, Burke MC, et al. Massachusetts emergency medicine closed malpractice claims: 1988-1990. Ann Emerg Med. 1993;22:553-559.
3. deWinter RJ, Koster RW, Sturk A, Sanders GT. Value of myoglobin, troponin T, and CK-MBmass in ruling out acute myocardial infarction in the emergency room. Circulation. 1995;12:3401-3407.
4. Keffer JH. Myocardial markers of injury: evolution and insights. Clin Chem. 1996;105:305-320.
5. Bernstein L, Spiekerman AM, Qamar A, et al. Effective resource management using clinical and laboratory algorithm for chest pain triage. Clin Lab Manage Rev. March/April 1996:143-152.
6. Adams JE, Bodor GS, Dávila-Román VG, et al. Cardiac troponin I: a marker with high specificity for cardiac injury. Circulation. 1993:88:101-106.
7. Ryan TJ, Anderson JL, Antman EM, et al. Management of acute myocardial infarction. J Am Coll Cardiol. 1996;28:1328-1428.
8. Bhayana V, Henderson AR. Biochemical markers of myocardial damage. Clin Biochem. 1995;28:1-29.
9. Wong SS. Strategic utilization of cardiac markers for the diagnosis of acute myocardial infarction. Ann Clin Lab Sci. 1996;26:301-312.
10. Selker HP, Zanlenski RJ, Antman EM, et al. National heart attack alert program report. Ann Emerg Med. 1997;29:63-69.
11. Montague C, Kircher T. Myoglobin in early evaluation of acute chest pain. Am J Clin Pathol. 1995;104:472-476.
12. Chernecky CC, Berger BJ. Laboratory Tests and Diagnostic Procedures. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1997:745-746.
13. Griffiths JC. Myoglobin: a small protein with a rapid release from tissue. Paper presented at: Emergency Cardiology Symposium; May 1996; Atlanta, Ga.
14. Vaananen HK, Syrjala H, Rahkila P, et al. Serum carbonic anhydrase III and myoglobin concentrations in acute myocardial infarction. Clin Chem. 1990;36:635-638.
15. Brogan GX, Vuori J, Friedman S, et al. Improved specificity of myoglobin plus carbonic anhydrase assay versus that of creatine kinase-MB for early diagnosis of acute myocardial infarction. Ann Emerg Med. 1996;27:22-28.
16. Van de Werfe F. Cardiac troponins in acute coronary syndromes. N Engl J Med. 1996;335:1388-1389.
17. Brown CS, Bertolet BD. Cardiac troponin: see you later CK [editorial]. Chest. 1997;111:2-4.
18. Antman EM, Tanasijovic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335:1342-1349.
19. Mair J, Genser N, Morandell D, Maier J, et al. Cardiac troponin I in the diagnosis of myocardial injury and infarction. Clin Chim Acta. 1996:245:19-38.
20. Antman EM, Grudzien C, Sacks DB. Evaluation of a rapid bedside assay for detection of serum cardiac troponin T. JAMA. 1995;273:1279-1282.
21. Martins JT, Li DJ, Baskin LB, et al. Comparison of cardiac troponin I and lactate dehydrogenase isoenzymes for the late diagnosis of myocardial injury. Clin Chem. 1996;106:705-708.
22. Jaffe AS, Landt Y, Parvin CA, et al. Comparative sensitivity of cardiac troponin I and lactate dehydrogenase isoenzymes for diagnosing acute myocardial infarction. Clin Chem. 1996;42:1770-1776.
23. Gerhardt W, Ljungdahl L. Detection of myocardial damage by serial measurements of cardiac troponin T, CK-MBmass, and TROPT rapid test. Cardiovasc Drug Ther. 1997;11 (suppl 1):227-240.
24. Wu AHB, Feng YJ, Moore R, et al. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. Clin Chem. 1998;44:1198-1208.
25. Bodor GS, Poterfield D, Voss EM, et al. Cardiac troponin-I is not expressed in fetal and healthy or diseased adult human skeletal muscle tissue. Clin Chem. 1995;41:1710-1715.
26. Apple FS, Sharkley SN, Hoeft P, et al. Prognostic value of serum cardiac troponin I and T in chronic dialysis patients: a 1-year outcome analysis. Am J Kidney Dis. 1997;29:399-403.
27. Apple FS, Voss E, Lund L, et al. Cardiac troponin, CK-MB and myoglobin for the early detection of acute myocardial infarction and monitoring of reperfusion following thrombolytic therapy. Clin Chim Acta. 1995;237:59-66.
28. Mair J, Smidt J, Lechleitner P, et al. A decision tree for the early diagnosis of acute myocardial infarction in nontraumatic chest pain patients at hospital admission. Chest. 1995;108:1502-1509.
29. Sayre MR, Gibler WB. New approaches to ruling out acute ischemic coronary syndrome in the emergency department. Ann Intern Med. 1996;27:75-78.
30. Tucker JF, Collins RA, Anderson AJ, et al. Value of serial myoglobin levels in early diagnosis of patients admitted for acute myocardial infarction. Ann Emerg Med. 1994;24:704-708.
31. Mair J, Morandell D, Genser N, Lechleitner P, Dienstl F, Puschendorf B. 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;41:1266-1272.
32. Ohman EM, Armstrong PW, Christenson RH, et al. Cardiac troponin T level for risk stratification in acute myocardial ischemia. N Engl J Med. 1996;335:1333-1341.
33. Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of subsequent events in unstable coronary artery disease. Circulation. 1996;93:1651-1657.
34. Wu AHB, Feng YJ, Contois JH, et al. Comparison of myoglobin, creatine kinase-MB, and cardiac troponin I for diagnosis of acute myocardial infarction. Ann Clin Lab Sci. 1996;26:291-299.
35. Adams JE, Sicard GA, Allen BT, et al. Diagnosis of perioperative myocar-
dial infarction with measurement of cardiac troponin I. N Engl J Med. 1994;330:670-674.
36. Bonnefoy E, Chevalier P, Kirkorian G, et al. Cardiac troponin I does not increase after cardioversion. Chest. 1997;111:15-18.
37. Georges JL, Spentchian M, Caubel C, et al. Time course of troponin I, myoglobin, and cardiac enzyme release after electrical cardioversion. Am J Cardiol. 1996;78:825-827.
38. Galvani M, Ottani F, Ferrini D, et al. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation. 1997;95:2053-2059.
39. Sylven C, Lindahl S, Hellkvist K, et al. Excellent reliability of nurse-based bedside diagnosis of acute myocardial infarction by rapid dry-strip creatine kinase MB, myoglobin, and troponin-T. Am Heart J. 1998;135:677-683.
40. Hamm CW, Goldmann BU, Heeschen C, et al. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med. 1997;337:1648-1653.
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