Educational Articles
In the Emergency Department, we use several criteria to identify an acute myocardial infarction. Traditionally, we look for a triad of chest pain, EKG abnormalities and elevations of serum biomarkers such as troponin, CK, CK-MB and myoglobin. As clinicians, we need to understand the appropriate tests, the proper application of these tests and how to properly interpret the results. These biomarkers also are the preferred markers in the setting of other injuries such as skeletal muscle trauma, muscle disease, cocaine use and many other disease states. The troponin complex is the main protein of the thin filament of the myofibrils. It is this protein that gets damaged in an ischemic event and this protein that we have developed immunoassays that detect the isoforms troponin T and troponin I to test for cardiac cell damage. This becomes a problem if we just depend on a troponin level to guide our diagnosis. In patients with low pretest probability of cardiac heart disease, elevations are not specific enough for an acute thrombotic event or disease and may be elevated in other diseases. These elevations may actually in some patients or cases cause us to make the wrong diagnosis or divert our attention away from the real underlying clinical problem and lead to unneeded invasive cardiac testing. Contemporary troponin assays are extremely sensitive and can detect very small amounts of myocardial necrosis in patients even without true myocardial infarction.

During long periods of ischemia, myocytes are irreversibly damaged. However, it is possible that cardiac troponins can be released into the blood without myocyte death. This might be due to conditions that cause increased myocyte permeability. With increased permeability, small troponin fragments could make it into systemic circulation. Troponin elevations have been reported in a multitude of different clinical scenarios other than an acute myocardial infarction. We need to consider three major categories:

1.) Injury that is multifactorial or of indeterminate cause
2.) Damage related to secondary myocardial ischemia
3.) Damage related to non-ischemic causes

Listed below are some causes other than an acute coronary event or syndrome that would or can cause an elevation in troponin.

  • Brady- or tachyarrhythmia, or a heart block
  • Coronary vasospasm
  • Hypertrophic cardiomyopathy
  • Cardiac contusion or other trauma
  • Cardioversion, defibrillator shocks, surgery, pacing
  • Critically ill patients especially those with diabetes, respiratory failure or sepsis
  • Acute neurological disease or injury
  • CHF (chronic as well as acute)
  • Renal failure
  • PE
  • Rhabdomyolysis with cardiac injury
  • Aortic Dissection
  • Inflammatory diseases
  • Infiltrative diseases
  • Drug toxicity or toxins
  • Burns
  • Exertion

As one can see, there are a multitude of things that can cause elevations in troponin levels or values. As clinicians, we need to be aware of all factors, so we don't over look the most common causes as well as some of the zebras (rare causes). The general population in studies tends to have very low levels of systemic or serum troponin, so if an individual has an elevated troponin, it bears further investigation. Remember there can be a small number of troponin elevations that are due to structural heart disease and not necessarily an acute process. There is the concept of "demand ischemia" where there is a mismatch in myocardial oxygen demand and supply. It was originally given to patients who had evidence of ischemia without any critical coronary damage or blockage. This refers to an event that is secondary to ischemia either due to increased oxygen demand or deceased oxygen supply. Common causes of decreased oxygen supply includes: coronary artery spasm, anemia, hypotension, hypertension or coronary embolism. The most common causes of an increase in oxygen demand is often seen in sepsis, septic shock, SIRS, atrial fibrillation or any tachyarrhythmia. Troponin elevations in critically ill (common in sepsis and SIRS) patients who often have no evidence of coronary heart disease are associated with worse outcomes.

Tachycardia can cause an elevation in troponin. In several studies, it was determined that the only reason found for the elevation in troponin levels was tachycardia whether due to illness or cardiac abnormality in conduction such as SVT. None of the patients had evidence of coronary heart disease (CHD). These studies demonstrated the release of myocardial troponin in the absence of CHD, inflammatory reasons and myodepressive factors. Left ventricular hypertrophy (LVH) can be a cause due to increased oxygen demand from increased muscle mass coupled with decreased flow secondary to microcirculation remodeling. Coronary vasospasm can also be a reason secondary to decreased blood flow and ischemia (an example can be seen in Prinzmetal's Angina). Atrial fibrillation can also cause elevations possibly due to inability to fill coronary arteries as needed resulting in demand ischemia due to decreased blood supply.

Acute neurological events such as acute stroke or intracranial hemorrhage can cause elevations in troponin and has been reported and correlated with severity of disease. One plausible reason is an imbalance in the autonomic nervous system allowing an increase of sympathetic activity. The elevation is less than that related to CHD, but it is still present.

Acute blunt trauma, whether directly to the myocardium or to the surrounding area, will cause a release of troponin according to one study, which followed serial EKGs and troponin over 8 hours. Only a very small percentage of the patients in the study went on to develop significant clinical complications due to cardiac injury. There are other direct injuries that can cause elevated troponin levels such as implanted cardioverter-defibulator shocks, high dose chemotherapy, infiltrative disorders such as amyloidosis (it is thought the amyloid deposits lead to compression of the cells causing damage) and inflammatory diseases such as pericarditis and myocarditis. Congestive heart failure can cause elevations via strain and cell death. Stress increased on the wall may lead to decreased subendocardial perfusion and cause an increased troponin level without an acute ischemic injury. This strain could be a reason in ultra-endurance events normal persons have had elevated troponin levels without an ischemic cardiac event. Catecholamine-induced vasospasm has also been thought to cause elevation in these persons.

Pulmonary disease can also cause elevations and are usually associated with significant right heart strain. In moderate to large PE, 30 -50% of patients will have elevated troponins and again this is thought to be due to right heart strain/overload. The troponin elevations usually resolve within 40 hours in comparison to longer elevated levels seen with acute myocardial injury. COPD exacerbation can also cause increased troponin levels as well as chronic kidney disease. End-stage renal disease patients frequently have persistent elevations of troponin. This could be due to high prevalence of heart disease in this population and not any reduced renal clearance. There is predominance in the elevation of isoform T over I in dialysis patients and is an independent indicator of mortality or morbidity. One last thing we will mention is that severe burns, greater than 25 percent of total body surface area, will cause elevated cardiac troponin levels. These elevations do not seem related to pre-existing medical conditions or age but directly to the extent of the burn.

Troponin is a highly sensitive biomarker, which can aid in the detection of myocardial cell damage due to thrombotic obstruction of a coronary artery or myocardial infarction. While troponin maybe useful to "rule out" a non-ST elevation myocardial infarction, the clinician must recognize the limitations of an elevated troponin to "rule-in" MI in patients with low clinical likelihood of an acute coronary syndrome (ACS). It is imperative that the clinician recognizes that troponin levels can be elevated in the absence of an ACS and further workup may be needed to identify the true pathology. Patients with low pretest probability for ACS are unlikely to get any benefit from a treatment strategy directed at coronary thrombosis and treating the underlying cause of troponin elevation is necessary to improve the condition of the patient. Remember that all elevated troponins are not due to an acute myocardial infarction.

*References available upon request.