In the diagnosis of acute myocardial infarction (AMI), Troponin I (cTnI), CK-MB, and Myoglobin (Myo) each have irreplaceable value. cTnI offers the best sensitivity and specificity but appears relatively late in the blood. Its long half-life is an advantage for detection but also has drawbacks. CK-MB appears in the blood at a similar time to cTnI but has a shorter half-life, making it useful for detecting secondary infarctions. Myo is the only marker suitable for early diagnosis (< 2 hours). Compared to testing cTnI, CK-MB, or Myo individually, the triple test combining all three holds greater clinical value.
Distinctive Features of cTnI
Advantages:
High sensitivity
High negative predictive value (NPV)
Strong specificity, exclusively related to cardiac cell death
Long half-life, persists in the bloodstream for an extended period
Disadvantages:
Late appearance in blood (> 3 hours post-onset), limiting its utility for early detection.
Due to its long half-life, a single cTnI test makes it difficult to detect a secondary infarction occurring within 2-4 days after the first event.
Elevated cTnI is not always caused by AMI; it may result from:
Atrial fibrillation
Hypertension
Kidney disease
Liver disease
Lung disease
Severe allergies
Distinctive Features of CK-MB
Advantages:
Returns to normal levels within 2-3 days post-infarction. It rises again if a secondary infarction occurs, offering unique value for detecting re-infarction during this period when cTnI from the initial event may still be elevated.
Can be used to estimate the extent of myocardial necrosis [1].
Provides valuable reference information when cTnI test results are unreliable or subject to interference.
A certain percentage of cases show cTnI-negative but CK-MB-positive results [2, 3].
Disadvantages:
Late appearance in blood (> 3 hours post-onset), limiting its utility for early detection.
Elevations can also occur in conditions other than AMI, such as skeletal muscle damage [4].
Distinctive Features of Myo
Advantages:
The only marker suitable for early detection of AMI (within < 3 hours of symptom onset).
When used in a serial testing protocol within < 3 hours of onset, it can achieve a 99% negative predictive value for AMI [5].
Disadvantages:
Short duration of elevation (returns to normal within 1-1.5 days), making it unsuitable for patients presenting late after symptom onset.
Poor specificity; elevations can occur in other conditions, including [6]:
Skeletal muscle dystrophies
Trauma, injury, burns
Myositis
Acute or chronic kidney disease
Intramuscular injections
The Triple Test (cTnI/CK-MB/Myo)
Rule out AMI within 2 hours in the Emergency Department
Negative Predictive Value (NPV): 100%
Significance:
Rapid exclusion of AMI
Risk stratification for AMI
Protocol:
Perform the triple cardiac marker test immediately upon patient presentation (0 hours).
Perform the triple cardiac marker test again at the 2-hour time point.
Rule out AMI: All of the following conditions must be met:
a. Myo increase from 0 to 2 hours < 50%
b. Myo negative
c. cTnI negative
d. CK-MB negative.
Do not rule out AMI: If any one of the above conditions (a, b, c, or d) is positive.
References
[1] Delanghe JR, De Mol AM, De Buyzere ML, et al. Mass concentration and activity concentration of creatine kinase isoenzyme MB compared in serum after acute myocardial infarction. Clin Chem 1990;36:149-53.
[2] Elizabete Silva dos Santos, Valéria Troncoso Baltar, Marcos Paulo Pereira, Luiz Minuzzo, Ari Timerman, Álvaro Avezum. Comparison between Cardiac Troponin I and CK-MB Mass in Acute Coronary Syndrome without ST Elevation.
[3] Kimberly C. Yee, MD, Debabrata Mukherjee, MD, Dean E. Smith, PhD, Eva M. Kline-Rogers, RN, Jianming Fang, MD, Rajendra H. Mehta, MD, Yassar Almanaseer, MD, Eyad Akhras, MD, Jeanna V. Cooper, MS, and Kim A. Eagle, MD. Prognostic Significance of an Elevated Creatine Kinase in the Absence of an Elevated Troponin I During an Acute Coronary Syndrome. The American Journal of Cardiology Vol. 92 Dec. 15, 2003.
[4] Characteristics of Cardiac Markers. Barnard Health Care. https://www.barnardhealth.us/emergency-medicine/table-477-characteristics-of-cardiac-markers.html. Accessed 18 Aug 2016.
[5] Pierce GF, Jaffe AS. Increased creatine kinase MB in the absence of acute myocardial infarction. Clin Chem 1986;32:2044-2051.
[6] Plebani M, Zaninotto M. Diagnostic strategies using myoglobin measurement in myocardial infarction. Clin Chim Acta 1998;272:69-77.
[7] James McCord, MD; Richard M. Nowak, MD, MBA; Peter A. McCullough, MD, MPH; Craig Foreback, PhD; Steven Borzak, MD; Glenn Tokarski, MD; Michael C. Tomlanovich, MD; Gordon Jacobsen, MS; W. Douglas Weaver, MD. Ninety-Minute Exclusion of Acute Myocardial Infarction By Use of Quantitative Point-of-Care Testing of Myoglobin and Troponin I. Circulation September 25, 2001, pp 1483-1488.
[8] Stephen PJ Macdonald and Yusuf Nagree. Rapid risk stratification in suspected acute coronary syndrome using serial multiple cardiac biomarkers: A pilot study. Emergency Medicine Australasia (2008) 20, 403–409.
[9] Alan S. Maisel, M.D., Karine Temple, M.N., Arthur Lover, M.N., Paul Clopton, M.S. A Prospective Study of an Algorithm Using Cardiac Troponin I and Myoglobin as Adjuncts in the Diagnosis of Acute Myocardial Infarction and Intermediate Coronary Syndromes in a Veteran's Hospital. Clin. Cardiol. 23, 915-920 (2000).
[10] Metachem Diagnostics Ltd. 29 Forest Road, Piddington, Northampton. NN7 2DA, United Kingdom. Tel. (01604)870370 Fax (01604) 870194.
[11] 7018 Owensmouth Ave. Suite 103 Canoga Park, CA, 91303, USA. Phone: 818-710-1281 Fax: 818-936-0121.
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