The diagnosis of cardiac emergencies is one of the most crucial tasks delegated to the emergency physician. The broad differential diagnosis of chest pain must be narrowed down quickly and accurately to perform the life-saving treatments patients require. Along with the history and physical exam, there are a number of important diagnostic tools that are used to differentiate the different causes of chest pain. One tool that has become an essential component of cardiac workups and diagnosis is the measurement of troponins. Interval troponin measurements have revolutionized the practice of emergency medicine and the way myocardial ischemia is diagnosed and treated.[1][2][3][4][5]

Troponins are cardiac regulatory proteins that are found in the cytoplasm of cardiac myocytes. When calcium binds to the protein complex, the structure of troponin changes, and this causes an interaction between the actin and myosin filaments. This interaction leads to cardiac muscle contraction. The troponin complex is made up of 3 subunits: cTnC, cTnI, and cTnT. cTnI and cTnT are the subunits that are identified in laboratory testing looking for cardiac muscle injury. cTnI has been shown to be exclusive to cardiac muscle. Studies have failed to identify cTnI in any body tissue at any point during neonatal development. Small amounts of cTnT have been identified in skeletal muscle but are found in much higher concentrations in cardiac muscle. In clinical studies, there have been no statistically significant differences found when using cTnI vs. cTnT in troponin assays.

Before troponin, there were a number of different cardiac biomarkers that were used to identify myocardial ischemia. In the 1960s and 1970s, biomarkers such as aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatinine kinase (CK) were used but were phased out due to lack of specificity for cardiac muscle. The next generation of biomarkers was more specific to cardiac muscle and included CK-MB and LDH 1+2. However, these markers still had an unacceptably high false-positive rate, and a new, more specific biomarker was needed. Troponins were first identified in 1965, but a reliable immune-assay to detect its levels in the blood was not developed until the late 1990s. Troponin measurements were found to have a near 100% sensitivity when checked 6 to 12 hours after the start of chest pain and have a significantly improved specificity for cardiac muscle damage when compared to previous biomarkers. Due to its clinical usefulness, serial troponin testing was added to the Third Universal Definition of Myocardial Infarction, which is the current definition used by the American College of Cardiology.[6][7][8]

Myocardial infarction occurs when blood flow is blocked in the coronary vessels that supply the heart muscle with oxygen. This causes a mismatch where oxygen supply is not meeting the oxygen demand of the myocytes, leading to necrosis and cell death. During this process, the cell membranes are ruptured, causing intracellular contents to spill into the extracellular space, eventually making their way into the bloodstream. If these cellular contents, including troponins, are spilled in large enough quantities that can be detected in the circulating blood.

There is a basal amount of troponin found in the circulation of healthy individuals from a normal turnover of cardiac myocytes. For a measured troponin to indicate pathophysiologic muscle damage, it must be greater than the 99th percentile of the normal range, which is about 3 standard deviations from the mean. According to the Third Universal Definition of Myocardial Infarction, there also must be a characteristic rise and fall of the troponin level measured over hours and days. Troponin levels typically start to elevate in the circulation within 2 to 3 hours of the onset of chest pain. The levels will continue to rise at that time until a peak is reached, generally between 12 and 48 hours. The troponin level will then begin to fall over the next 4 to 10 days down to a normal level. This expected rise and fall of the troponin is an important factor that can distinguish a myocardial infarction from other causes of elevated troponins.

In the emergency department setting, it is impossible to follow troponin levels completely from rising to peak to fall. When a patient presents complaining of chest pain, a diagnostic decision has to be made promptly. To help guide decision making in the emergency setting, myocardial infarctions are divided into 2 categories using ECG findings; ST-segment elevation myocardial infarctions (STEMI) and non-ST segment elevation myocardial infarctions (NSTEMI). In STEMIs, patients will have an elevated troponin as well as one of the following ECG changes: (1) ST-segment elevations greater than 1 mm in contiguous leads with reciprocal changes, (2) new evidence of a left bundle branch block, or (3) ST-segment elevations noted on a posterior ECG. In this scenario, the diagnostic and therapeutic decisions are simple. The patient likely has a major blockage of a coronary vessel and requires emergent coronary catheterization if available or thrombolytic therapy to open the blocked vessel and reperfuse the cardiac muscle.

NSTEMIs are defined as an injury to the cardiac muscle that results in an elevated troponin but lacks the ECG changes that define a STEMI. NSTEMIs usually represent less myocardial tissue damage than STEMIs, and an emergent coronary catheterization is not needed initially. NSTEMIs are generally treated with medical management including dual antiplatelet therapy as well as full anticoagulation such as heparin. NSTEMIs present a difficult challenge to the emergency physician. It is possible that a patient with chest pain can have a negative troponin initially with no ECG changes but can still have an NSTEMI because troponin levels do not start to rise until at least 2 to 3 hours after the initial insult. This emphasizes the importance of getting serial troponins spaced 3 to 6 hours apart in patients suspected of having an ischemic event but have a troponin that is initially normal.