Troponins I and T are two subunits of a larger regulatory protein complex that plays an important role in the activity of cardiac and skeletal smooth muscle. When intracellular concentrations of calcium increase, troponin facilitates actin-myosin interaction by binding to the inhibitory protein tropomyosin, allowing coordinated contraction of muscle fascicles (myofibrils) and the generation of meaningful force. (1, 2) Currently, multiple assays exist for the detection of both troponin I and troponin T, including high sensitivity assays that are currently pending approval in the United States. (3) These high-sensitivity assays allow for the more-timely diagnosis of smaller myocardial injuries, further expediting time to disposition. In general, however, these assays vary slightly in terms of target protein and are largely considered interchangeable. Following myocardial injury, serum troponin levels typically begin to rise after roughly two hours and reach peak serum levels at approximately 24-36 hours with gradual clearance over the subsequent 7-10 days. (2)
Creatine kinase (CK) - otherwise known as creatine phosphokinase (CPK) - is an enzyme expressed in numerous tissues. Creatine kinase acts by phorsphorylating creatine to create phosphocreatinine using adenosine triphosphate (ATP), thereby providing an energy reservoir in metabolically active cells. (4) Typical CK assays assess the proportions of various isoenzymes present within serum; the MB isoenzyme is disproportionately expressed in myocardial tissue, and CK-MB percentages exceeding 15-30% of total serum CK are highly suggestive of myocardial injury. (5) Unfortunately, CK-MB is synthesized in various other organ systems - including the prostate, uterus, stomach - limiting its specificity. CK-MB elevations are generally detectable within 4-6 hours following cardiomyocyte death, and peak within 9-12 hours. (6, 7) CK-MB is generally cleared from the serum within 36-48 hours. (8) Due to its limited specificity, CK-MB has largely been replaced by serum troponin levels in the diagnosis of acute myocardial infarction.
Other serum biomarkers of myocardial injury exist - including myoglobin, copeptin, and LDH - but will not be discussed further here, as they have largely been replaced with serum troponin.
Definition of Myocardial Infarction
Despite the ubiquity of cardiovascular disease and frequent discussion of/assessment for myocardial injury within the emergency department, it may behoove emergency physicians to familiarize themselves with the formal definition of myocardial infarction as defined in the Third Universal Definition of Myocardial Infarction, a consensus document between multiple eminent organizations dedicated to cardiovascular health. (9)
The formal definition of myocardial infarction is as follows:
Other considerations include non-ST-elevation myocardial infarction (wherein patients exhibit serum biomarkers suggestive of MI without concomitant electrocardiographic changes) and unstable angina (patients with concerning symptoms and/or electrocardiographic changes but normal cardiac biomarker levels).
Types of Cardiomyocyte Injury (9)
Cardiologists have compiled different forms of cardiomyocyte injury into five primary categories based on the underlying pathophysiology. While the precise identification of the underlying pathophysiology is not always critical to patient care and disposition with the emergency department, familiarity with these classifications of myocardial injury may facilitate better clarity in interdisciplinary communication.
MI Type 1 - Spontaneous Myocardial Infarction
The classical definition of cardiomyocyte necrosis secondary to vascular occlusion and/or ischemic insult. These mechanisms include atherosclerotic plaque rupture, thrombus formation, dissection, and many others all precipitating significant myocardial injury.
MI Type 2 - Ischemic Imbalance
Commonly referred to as “demand ischemia,” wherein physiologic work of the heart exceeds the hearts ability to autoperfuse, leading to imbalance in oxygen supply and/or demand. Of note, this ischemia should stem from a pathophysiologic process OTHER than coronary artery disease to truly be categorized as Type 2. Such conditions may stem from large volumes of circulating endogenous/exogenous catecholamines, such as sepsis, sympathomimetic abuse, or postoperatively.
MI Type 3 - Cardiac Death due to Suspected Myocardial Infarction
Type 3 refers specifically to patients who progress to cardiovascular collapse and ultimate death without objective identification of myocardial injury. These patients often present with symptoms highly suggestive of cardiomyocyte injury - e.g., chest pressure, diaphoresis, nausea, shoulder pain, and/or concerning electrocardiographic findings - but expire prior to confirmation with serum biomarkers.
MI Types 4/5 - Myocardial Injury following Cardiac Intervention
These two classes may be lumped together as they refer to cardiomyocyte necrosis following percutaneous intervention (PCI) and coronary artery bypass graft (CABG), respectively. Patients who undergo some form cardiac intervention are, by definition, at increased risk of myocardial injury; these procedures carry some implicit risk of further exacerbating the underlying pathology or precipitating new disease. MI Type 4 is often subdivided into 4a (injury secondary to PCI alone) and 4b (injury secondary to stent thrombosis).
- Fox, W. R., & Diercks, D. B. (2016). Troponin assay use in the emergency department for management of patients with potential acute coronary syndrome: current use and future directions. Clinical and Experimental Emergency Medicine, 3(1), 1-8. doi:10.15441/ceem.16.120
- Rahman, A., & Broadley, S. A. (2014). Review article: Elevated troponin: Diagnostic gold or fool's gold? Emergency Medicine Australasia, 26(2), 125-130. doi:10.1111/1742-6723.12203
- Hollander, J. E., M.D. (2016). Managing Troponin Testing. Annals of Emergency Medicine, 68(8), 690-694.
- Creatine Kinase. (n.d.). Retrieved March 15, 2017, from https://meshb.nlm.nih.gov/#/record/ui?name=Creatine%20Kinase
- Guzy, P. M. (1977, December). Creatine Phosphokinase-MB (CPK-MB) and the Diagnosis of Myocardial Infarction. Western Journal of Medicine.
- Zabel, M., Hohnloser, S. H., Koster, W., Prinz, M., Kasper, W., & Just, H. (1993). Analysis of creatine kinase, CK-MB, myoglobin, and troponin T time- activity curves for early assessment of coronary artery reperfusion after intravenous thrombolysis. Circulation, 87(5), 1542-1550. doi:10.1161/01.cir.87.5.1542
- Puleo, P.R., et al. (1990) Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB. Circulation, 82(3):759-64.
- Jaffe, A.S., et al. (1996) Comparative sensitivity of cardiac troponin I and lactate dehydrogenase isoenzymes for diagnosing acute myocardial infarction. Clinical Chemistry, 42(11):1770-6.
- Thygesen, K., Alpert, J. S., Jaffe, A. S., Simoons, M. L., Chaitman, B. R., & White, H. D. (2012). Third Universal Definition of Myocardial Infarction. Circulation, 126(16), 2020-2035. doi:10.1161/cir.0b013e31826e1058
- Subforms of Creatine Kinase MB in the Diagnosis of Myocardial Infarction. (1995). New England Journal of Medicine, 332(9), 608-610.
- Amsterdam, E. A., et al. On behalf of the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Cardiovascular Nursing, and Interdisciplinary Council on Quality of Care and Outcomes Research. (2010). Testing of Low-Risk Patients Presenting to the Emergency Department With Chest Pain.
- Perivandi, A. A., et al. (2004). Comparison of cardiac troponin I versus T and creatine kinase MB after coronary artery bypass grafting in patients with and without perioperative myocardial infarction. Herz, 29(7):658-64.
Written by: Matthew Scanlon, MD PGY-1
Edited and Posted by: Jeffery Hill, MD MEd