Patients presenting with a poor history are usually taken through multiple blood tests that may also include troponins, which may be positive due to cardiac demand mismatch rather than ACS. It is these types of patients in whom troponin elevations must be viewed with caution. It is true that generally the presence of elevated biomarkers draws attention to definite myocardial injury and needs to be differentiated from ACS. Myocardial injury, without any history of chest pain, or an atypical presentation without ECG changes, cannot be truly defined as ACS. In such cases, other underlying causes for myocardial injury must be investigated. This review draws attention to these nonACS causes of troponin elevation.
Troponins
Troponin is a regulatory protein complex that participates in muscle contraction between myosin and actin. It is found in cardiac and skeletal muscle, but not in smooth muscle. There are 3 different protein components—T, C, and I—of the troponin complex. Troponin T is located directly over the myosin-binding sites on the tropomyosin, which is wrapped around the actin thin filament. Troponin C binds to calcium and allows troponin T to expose the myosin-binding sites. Troponin I is an inhibitory protein that prevents calcium from binding troponin C. This troponin complex is the primary regulator of calcium-and adenosine triphosphate (ATP)-dependent myocardial contraction. When an action potential passes through the muscle, calcium channels are opened, releasing calcium from the sarcoplasmic reticulum into the sarcoplasm. Calcium then binds to troponin C, altering its shape and exposes the myosin-binding sites. Different types of muscle have their own unique troponin complexes, particularly the troponin C subunit. There are 3 calcium-binding sites on the troponin C subunit of cardiac myocytes, whereas there are 4 in skeletal muscle.
DETECTION OF TROPONINS
Troponins in the blood are detected by immunoassays that use cardiac troponin-specific antibodies and are quantified by the same immunoassay methods. The newest generation of assays testing for cardiac troponins is very sensitive in detecting trace levels of troponin in the blood. When cardiac myocyte injury occurs, cell membrane is compromised, leading to the release of the intracellular proteins into the bloodstream. Troponin detection in the blood signifies a break in myocardial cell membrane integrity, not a coronary occlusion; the troponin leak may be due to demand mismatch. Hence, a troponin leak occurs due to break in the cell integrity due to other mechanisms as discussed later and not necessarily related to MI secondary to CAD. Cardiac troponin levels measured by immunoassay methods detect the troponin in the bloodstream but cannot define the mechanisms of heart muscle cell injury.
Noncardiac Causes of Troponin Release
Recent papers and studies have shown that noncoronary events and other noncardiac conditions, eg, endstage renal disease, acute pulmonary embolism (PE), acute pericarditis, neurologic strokes, hypertensive crises, and sepsis have all led to release of troponin in the bloodstream that is readily detectable by laboratory testing.1 Thus, cardiac troponin levels merely indicate the break of cardiac muscle cell membrane integrity or injury and do not necessarily point to the mechanism of myocardial damage. Hence, when a patient in an ED presents for a noncardiac reason, the patient’s troponin level may be elevated due to other causes. While one would intuitively want to rule out cardiac etiology, it is equally important not to overlook the overall patient’s clinical picture. A good history and physical examination that focuses on other conditions is important so that the patient’s primary clinical diagnosis is not left untreated. In addition, putting emphasis only on a lab value of an elevated troponin may lead to increased hospitalizations and unnecessary cardiac testing when ACS is unlikely to be the cause of an isolated troponin elevation. Thus, as important as it is to not miss an ACS, it is equally important to recognize other causes of elevated troponin.
Chest Discomfort as a Presenting Symptom
When a patient complains of chest discomfort, a suspicion of ACS is raised. The differential diagnosis, however, can range from a musculoskeletal pain to an acute MI, or may be a pain referred from a distant area, such as an abdominal organ. Cardiac enzyme levels are measured in these cases when suspicious. In addition, cardiac enzymes are also measured routinely in other atypical presentations that may be considered to be cardiac in origin, including loss of consciousness, dizziness, or dyspnea. This leads to a need for a list of differential diagnoses. In case of CAD, the suspicion for a coronary event is high when a patient has a documented history of CAD and presents with an atypical chest pain; however, the differential diagnoses are generally broad and include musculoskeletal pain, congestive heart failure (CHF) exacerbation, pulmonary event, chronic obstructive pulmonary disease (COPD) exacerbation, hypertensive urgency, infection, vascular event, central nervous system event, or even an abdominal event that need not be overlooked.
Table 1 is a brief summary of the different causes of cardiac troponin elevation, which include many nonACS causes. There are several conditions that have detectable troponin in the bloodstream in the absence of ACS or acute MI.2 These are considered to be due to demand mismatch, myocardial cell irritation, infiltration of the myocardial cells, or direct trauma to the myocardial cell membrane. These conditions, when present, need to be recognized and dealt with when the presentation is somewhat atypical for a coronary event. These causes of troponin elevation have also been classified as MI.3