Laboratory Diagnosis of Myocardial Infarction

     

A number of laboratory tests are available. None is completely sensitive and specific for myocardial infarction, particularly in the hours following onset of symptoms. Timing is important, as are correlation with patient symptoms, electrocardiograms, and angiographic studies. The following tests are available as markers for acute myocardial infarction:

     

Creatine Kinase - Total:

The total CK is a simple and inexpensive test that is readily available using many laboratory instruments. However, an elevation in total CK is not specific for myocardial injury, because most CK is located in skeletal muscle, and elevations are possible from a variety of non-cardiac conditions.

     

Creatine Kinase - MB Fraction:

Creatine kinase can be further subdivided into three isoenzymes: MM, MB, and BB. The MM fraction is present in both cardiac and skeletal muscle, but the MB fraction is much more specific for cardiac muscle: about 15 to 40% of CK in cardiac muscle is MB, while less than 2% in skeletal muscle is MB. The BB fraction (found in brain, bowel, and bladder) is not routinely measured.

Thus, CK-MB is a very good marker for acute myocardial injury, because of its excellent specificity, and it rises in serum within 2 to 8 hours of onset of acute myocardial infarction. Serial measurements every 2 to 4 hours for a period of 9 to 12 hours after the patient is first seen will provide a pattern to determine whether the CK-MB is rising, indicative of myocardial injury. The CK-MB is also useful for diagnosis of reinfarction or extensive of an MI because it begins to fall after a day, dissipating in 1 to 3 days, so subsequent elevations are indicative of another event.

A "cardiac index" can provide a useful indicator for early MI. This is calculated as a ratio of total CK to CK-MB, and is a sensitive indicator of myocardial injury when the CK-MB is elevated.

 

CK-MB Isoforms:

The CK-MB fraction exists in two isoforms called 1 and 2 identified by electrophoretic methodology. The ratio of isoform 2 to 1 can provide information about myocardial injury.

An isoform ratio of 1.5 or greater is an excellent indicator for early acute myocardial infarction. CK-MB isoform 2 demonstrates elevation even before CK-MB by laboratory testing. However, the disadvantage of this method is that it is skilled labor intensive because electrophoresis is required, and large numbers of samples cannot be run simultaneously nor continuously. False positive results with congestive heart failure and other conditions can occur.

 

Troponins:

Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB.

Troponins will remain elevated longer than CK--up to 5 to 9 days for troponin I and up to 2 weeks for troponin T. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or extension of infarction in a patient who has already suffered an initial MI. Troponin T lacks some specificity because elevations can appear with skeletal myopathies and with renal failure.

 

Myoglobin:

Myoglobin is a protein found in skeletal and cardiac muscle which binds oxygen. It is a very sensitive indicator of muscle injury. The rise in myoglobin can help to determine the size of an infarction. A negative myoglobin can help to rule out myocardial infarction.. It is elevated even before CK-MB. However, it is not specific for cardiac muscle, and can be elevated with any form of injury to skeletal muscle.

 

Lactate dehydrogenase:

The LDH has been supplanted by other tests. It begins to rise in 12 to 24 hours following MI, and peaks in 2 to 3 days, gradually dissipating in 5 to 14 days. Measurement of LDH isoenzymes is necessary for greater specificity for cardiac injury. There are 5 isoenzymes (1 through 5). Ordinarily, isoenzyme 2 is greater than 1, but with myocardial injury, this pattern is "flipped" and 1 is higher than 2. LDH-5 from liver may be increased with centrilobular necrosis from passive congestion with congestive heart failure following ischemic myocardial injury.

 

[References]

  1. Collinson PO, Chandler HA, Stubbs PJ, Moseley DS, Lewis D, Simmons MD. Measurement of serum troponin T, creatine kinase MB isoenzyme, and total creatine kinase following arduous physical training. Ann Clin Biochem. 1995;32:450-453.
  2. deWinter RJ, Koster RW, Sturk A, Sanders GT. Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room. Circulation. 1995;92:3401-3407.
  3. Gornall DA, Roth SN. Serial myoglobin quantitation in the early assessment of myocardial damage: a clinical study. Clin Biochem. 1996;29:379-384.
  4. Hossein-Nia M, Kallis P, Brown PA, et al. Creatine kinase MB isoforms: sensitive markers of ischemic myocardial damage. Clin Chem. 1994;40:1265-1271.
  5. Jaffe AS, Landt Y, Parvin CA, Abendschein DR, Geltman EM, Ladenson JH. Comparative sensitivity of cardiac troponin I and lactate dehydrogenase isoensymes for diagnosing acute myocardial infarction. Clin Chem. 1996;42:1770-1776.
  6. Levinson SS, Hobbs GA. Usefulness of various lactate dehydrogenase isoenzyme 1 profiles after myocardial infarction. Ann Clin Lab Sci. 1994;24:364-370.
  7. Mair J, Genser N, Morandell D, et al. Cardiac troponin I in the diagnosis of myocardial injury and infarction. Clin Chim Acta. 1996;245:19-38.
  8. Martins JT, Li DJ, Baskin LB, Jialal I, Keffer JH. Comparison of cardiac troponin I and lactate dehydrogenase isoenzymes for the late diagnosis of myocardial injury. Am J Clin Pathol. 1996;106:705-708.
  9. Mercer DW. A historical background in cardiac markers. Medical Laboratory Observer. 1996;July:45-51.
  10. Mullner M, Hirschl MM, Herkner H, et al. Creatine kinase-mb fraction and cardiac troponin T to diagnose acute myocardial infarction after cardiopulmonary resuscitation. J Am Coll Cardiol. 1996;28:1220-1225.
  11. Wu AH, Feng YJ, Contois JH, Pervaiz S. Comparison of myoglobin, creatine kinase-MB, and cardiac troponin I for diagnosis of acute myocardial infarction. Ann Clin Lab Sci. 1996;26:291-300. 

 

Troponin I - A Highly Specific Marker for Cardiac Muscle


The enzyme tests used for the diagnosis of myocardial infarction are CK and AST, with LDH being useful in delayed presentations. When the source of a raised CK is unclear, CKMB has been measured to confirm or rule out myocardial infarction.

Recently a more specific marker of myocardial injury has been described - Troponin I. Unlike CKMB which is found in small amounts in skeletal muscle, cardiac Troponin I is only found in cardiac muscle. Concurrent skeletal muscle injury in the presence of myocardial damage has sometimes posed a problem with CKMB since the CKMB index could give a false negative value in that situation. Not Troponin I. Therefore Troponin I is more sensitive than CKMB in detecting myocardial infarction or injury. CKMB may be falsely elevated in some chronic muscle diseases. Not Troponin I. Therefore Troponin I is more specific than CKMB. These properties make Troponin I the ideal test to confirm or rule out myocardial damage when the diagnosis is in doubt.

Troponin I becomes positive at about the same time as CKMB does ie 4-8 hours after a myocardial infarct. However unlike CKMB, Troponin I remains raised for 5-9 days after the event - permitting late diagnosis of MI and making LDH measurements redundant. CKMB normalises two days after the event.

Normal healthy people have undetectable levels of Troponin I in blood. However, sick patients may have minor increases in Troponin I. The reference range in our system (Abbott Axsym) is <2.0 ug/L. Marginal increases in Troponin I above 2.0 ug/L may be seen in unstable angina. It has been suggested that patients with unstable angina who have marginal increases in Troponin I have a significantly worse prognosis than patients with undetectable Troponin. Troponin I is now used in risk stratification and management of patients with unstable angina.

NB. Troponin I should be distinguished from Troponin T, a similar marker but which does not seem to be as specific as Troponin I for cardiac muscle damage.

Troponin I measured by the Stratus Dade method gives different concentrations, although there is very good correlation with the Abbott results. Much of the published data is based on the Dade method. The reference range for this method is <1.5ug/L.


Key References.

1. Cardiac Troponin I. A marker with high specificity for cardiac injury. Adams JE et al. Circulation 1993; 88: 101-106

2. Diagnosis of perioperative myocardial infarction with measurement of cardiac Troponin I. Adams JE et al. New England Journal of Medicine 1994; 330: 670-674

3. Cardiac specific Troponin I levels predict the risk of mortality in patients with acute coronary syndromes. Antman EM et al. New England Journal of Medicine 1996; 335: 1342-1349

[last reviewed February 1999]