Welcome to the sixth installment of “Inconceivable: medical terms that don’t mean what you think they mean.”
You are admitting a patient with chest pain. His EKG is unchanged from his prior and his Troponin is within normal limits, but he has multiple medical problems and a history concerning for acute coronary syndrome. When you call the admitting team, you report that the patient has negative cardiac enzymes. But does he? Surely we can’t have this one wrong, can we?
Cardiac Troponins are the gold standard for evaluation of acute coronary syndrome in the emergency department. Troponins are proteins, but they are not enzymes. Troponin I and T (which we will consider equivalent for our purposes) are present in the myocardium and in skeletal muscle. Interestingly, and fortunately for us and our patients, different genes encode these proteins in cardiac muscle than in skeletal muscle. This biochemical fun fact is taken advantage of in the current assays, and it makes Troponin much more specific than any of the other biomarkers that have been used for evaluation of chest pain.
Why is the term “cardiac enzymes” used then? Before the widespread use of Troponin, Creatine Kinase MB Isoenzyme (CK-MB) was the biomarker most commonly measured. Creatine Kinase (CK) is an enzyme – and therefore by definition also a protein – found in the myocardium, but also brain and skeletal muscle, among other places. CK is a dimer (dimer being a protein composed of two parts, not to be confused with D-dimer). Every CK enzyme is made of two halves, each half being either an “M” or “B” isoform. The MM form is found in cardiac and skeletal muscle; BB in brain, lung, and many other tissues; and MB primarily in cardiac tissue, but also skeletal muscle, diaphragm, small intestine, uterus, and prostate. This wide distribution of CK-MB limits its specificity in ACS evaluation.
The advent of Troponin has rendered CK-MB essentially useless in the emergency department, as CK-MB is both less specific and less sensitive than Troponin. The only real utility would be to determine the timing of an MI. When cardiac myocytes are fatally injured, they leak proteins. The level of a measured biomarker depends on many factors like molecular weight, blood flow to the injured area, and rate of elimination from the serum. Both Troponin and CK-MB rise in the serum 2 to 4 hours after cardiac injury, but CK-MB has a much shorter half-life. As such, if a patient were to have an elevated Troponin but normal CK-MB, it could indicate a very small MI or one that happened a few days ago. This may be of interest to our internal medicine or cardiology colleagues but is of limited concern to us in the ED.
Next time you are evaluating a patient with chest pain, be precise and remember that Troponin is a protein or a biomarker, not an enzyme.
Braunwald, E., & Bonow, R. O. (2012). Braunwald’s heart disease: A textbook of cardiovascular medicine. Philadelphia: Saunders.
Robbins, S. L., Kumar, V., & Cotran, R. S. (2010). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Saunders/Elsevier.
Dr. Krueger is currently an emergency medicine attending physician at Advocate Lutheran General Hospital and a former UIC EM Chief Resident.