Tsai SH, Chu SJ, Hsu CW, et al
Am J Emerg Med. 2008;26:331-341

Serum troponin (TN) testing has become routine in ED patients presenting with cardiopulmonary complaints. Elevated TN levels are now considered part of the defining criteria for diagnosis of acute myocardial infarction (MI).[1] However, while TN elevation is typically related to myocardial damage, it is not pathognomonic for acute coronary syndrome (ACS). There are actually quite a few other conditions in which TN levels may increase, especially to low or “marginal” levels. It’s important for emergency physicians (EPs) to be aware of these conditions so they do not inappropriately treat these patients for ACS. The authors provide a nice review of the various causes of TN elevations. This viewpoint will summarize the key points of the review without delving too much into pathophysiology. For readers who would like more on the underlying pathophysiology, please refer to the article.


Cardiac TNs are regulatory proteins in striated muscle and consist of 3 subunits: TN-T, TN-I, and TN-C. Striated muscle is present in skeletal and cardiac muscle. TN-C is also found in smooth muscle so it has the least cardiac specificity. In this viewpoint, the term “TN” will refer to TN-I and TN-T, not TN-C.

TN-I is considered the most cardiac-specific because it has not been identified in skeletal muscle. TN-T has been found in low levels in various skeletal muscle disorders. TN-T is also less specific for cardiac disease in the presence of renal failure. TNs may be elevated in the presence of reversible or irreversibly myocyte damage. This may be the result of ACS but also disorders of cardiac inflammation, intoxication, malignancy, or degeneration. For most of the causes of TN elevations, even marginal elevations are usually associated with an increased risk for adverse in-patient events and all-cause inpatient mortality.

Therefore, even if the patient does not have ACS, the TN elevation should heighten concern for complications and mortality in the patient, and strongly suggest an aggressive treatment plan. The majority of the non-ACS conditions listed below tend to cause rather low-level TN elevations, and usually they do not tend to cause the typical evolving rise-and-fall pattern of TN levels over 12 to 24 hours that are found in patients with true ACS. Therefore, when there is a question regarding whether a patient with an initially elevated TN level has ACS or not, it would be prudent to monitor changes in the electrocardiograph and serial TN levels to help make the distinction.

Cardiac Diseases

ACS. TN elevation has clearly been shown to correlate with adverse cardiac events as well as short-term and long-term mortality in patients with ACS. TN elevations should prompt more aggressive medical therapy of patients with ACS.

Congestive heart failure. TN elevations identify high-risk patients with poor short-term prognosis. Elevations are also associated with an increased risk for ventricular dysrhythmias, and when combined with elevations of B-type natriuretic peptide, predict increased inpatient mortality in patients with congestive heart failure (CHF).

Myocarditis and pericarditis. TN elevations are helpful in identifying myocyte necrosis associated with myocarditis, and elevations may also be found with pericarditis. Note that if a patient with pericarditis has TN elevations, it is often assumed that there is myocardial involvement as well (which is thus referred to as myopericarditis). Although TN levels do not correlate with prognosis in these patients, there is a good correlation between TN elevation and 1-month duration of heart failure symptoms.

Cardiomyopathy. TN elevations are often associated with the presence of dilated cardiomyopathy, peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, and Tako-tsubo cardiomyopathy (a type of cardiomyopathy associated with severe emotional stress). TN elevations are also associated with infiltrative cardiac disorders (eg, amyloid cardiomyopathy) and are better predictors of survival than symptoms or two-dimensional echocardiography.

Cardioversion/defibrillation. External or internal cardioversion/defibrillation does not seem to be associated with myocardial injury or “marked” elevations of TN levels. Even if there are more minor elevations of TN purely due to the shock, the levels should be low and should resolve quickly. Higher levels should indicate true acute MI.

Cardiac procedures. TN levels may be elevated after a prolonged PCI due to prolonged balloon inflation, but the significance of these levels is uncertain. Perioperative and especially postoperative TN elevations in patients undergoing CABG is associated with prognosis.

Cardiac trauma. Patients with TN elevations after blunt cardiac trauma have a higher risk of cardiac dysrhythmias and LV dysfunction. However, their prognosis is unrelated to the level. “Nondetectable TN levels in asymptomatic patients at admission and within the first 6 hours after admission can rule out relevant myocardial injury.” As noted below, however, TN elevations in these patients can also occur due to hemorrhage or shock.

Cardiotoxins. Bites by venomous snakes can cause acute MI or vasospasm, resulting in elevated TN levels. This is attributed to the direct myocardial effect of the venom’s toxin. The same phenomenon has been reported with jellyfish, scorpion, and certain insect stings.

Tachycardia. Severe tachycardia, even in the presence of normal coronary arteries, can induce elevations of TN due to increased myocardial oxygen demand and decreased myocardial oxygen supply.

Noncardiac Diseases

Sepsis. TN elevations in sepsis patients correlate with myocardial dysfunction in patients with critical illness. Postulated mechanisms for this include demand ischemia (due to increased oxygen demand related to increased cardiac output, tachycardia, or use of pressors); release of myocardial depressants (eg, tumor necrosis factor-alpha, interleukin 1, interleukin 6); and direct cardiac myocytotoxic effects of endotoxins, cytokines, or reactive oxygen radicals induced by the infectious process. Regardless of the cause, high TN levels predict increased severity of sepsis, prolonged intensive care unit length of stay, and increased mortality.

Pulmonary embolism. TN elevations in patients with pulmonary embolism (PE) predict a complications and mortality. Many propose that TN elevations in the presence of PE may warrant more aggressive therapy, such as thrombolytics, although good outcome studies related to this proposal are lacking. Large PEs induce acute right ventricular pressure overload, which causes increased wall tension and regional wall ischemia. This is proposed as a potential reason for the TN release.

Chronic obstructive pulmonary disease. Severe exacerbations of COPD are associated with acute right ventricular strain and can therefore produce TN release through a similar mechanism as that proposed for PE. Alternatively, patients with chronic obstructive pulmonary disease (COPD) exacerbations may have concurrent acute MI, CHF, or PE and therefore have elevated TN levels. TN elevations correlate with the severity of the COPD exacerbation and length of hospital stay.

Carbon monoxide poisoning. TN elevations may occur in CO poisoning and is likely related to myocardial hypoxia and injury.

Intracranial abnormalities. TN elevations may occur in patients with intracranial (IC) abnormalities due to sympathetic overstimulation and/or altered autonomic tone associated with these disorders. Elevated IC pressure, for example, leads to marked increases in catecholamine output, which induces tachycardia, coronary vasospasm, vasoconstriction, and intracellular calcium increases, which have direct myocardial toxic effects.

  • Subarachnoid hemorrhage (SAH): Higher Hunt-Hess grade, female gender, larger body surface area, larger left ventricular mass, lower systolic blood pressue (SBP), and higher heart rate in patients with SAH are all predictors of TN elevation. Hypothalamic stress from SAH results in large releases of catecholamines, which may result in myocardial damage. Elevated TN levels in patients with SAH correlate with risk for cardiopulmonary complications, delayed cerebral ischemia, worse functional outcomes at discharge, and death;
  • Acute ischemic stroke: TN elevation at admission in patients with stroke is associated with increased risk of in-hospital cardiac complications and mortality;
  • IC hemorrhage: TN elevation in patients with IC hemorrhage is an independent predictor of increased in-hospital mortality; and
  • Epilepsy and seizures: TN levels may be elevated in patients with persistent seizures. Plasma catecholamines can reach 12-40 times normal within minutes in seizing patients. These elevated catecholamine levels in combination with metabolic acidosis, increased oxygen demand, diffuse cerebral stimulation, and cerebral edema can produce TN elevations. Although a direct prognostic value of elevated TN in patients with seizures has not been found, TN elevations should not be ignored: generalized seizures are known to be a significant physiological “stress test” and can induce acute MI in patients with pre-existing coronary disease. Further ACS workup should ensue in these patients.

End-stage renal disease. Patients with end-stage renal disease may have chronically elevated TN levels due to ongoing myocyte damage and “micromyocardial infarction.” Even in the absence of acute MI, TN levels may be elevated. Elevated TN-T levels may persist even after hemodialysis in these patients, but the authors state that TN-I should not follow this pattern. TN-I levels should decrease after hemodialysis. Regardless of whether the TN elevations are chronic, any elevation of TN predicts a high risk for overall mortality and major adverse cardiac events at 2 years, even in asymptomatic patients. In acutely ill hemodialysis-dependent patients, an elevated TN level predicts an increased 30-day cardiac risk regardless of the presentation.

Rhabdomyolysis. Emergency department patients presenting with rhabdomyolysis often have positive TN levels. These levels do not correlate well with serum creatine phosphokinase levels, renal failure, degree of muscle damage, or cardiovascular risk factors. The TN levels may be related to the underlying cause of rhabdomyolysis (eg, cocaine toxicity, hypotension, sepsis, etc). Elevated TN levels correlate with hospital length of stay and morbidity.

Eclampsia and preeclampsia. Pregnant women with hypertensive disorders have elevated TN levels. Levels seem to correlate with the presence of proteinuria.

Extreme endurance exercise. TN elevations occur in up to one third of individuals participating in prolonged strenuous exercises (eg, marathons, triathlons, etc). There does not seem to be an association with adverse cardiac outcomes in these patients.

Other causes. Some of the other non-ACS conditions listed in the article without discussion that are associated with TN elevations include

  • Upper gastrointestinal bleeding;
  • Left ventricular hypertrophy; and
  • Catecholamine toxicity.

False-Positive Results

As with any test, there is the potential for false-positive results. These results can occur “due to cross-reaction with other plasma components such as high serum levels of free hemoglobin or bilirubin or to interference with autoantibodies [against the TN complex], heterophilic antibodies, or rheumatoid factor. Fibrin residuals and other microparticles can also interfere with TN determinations.”


  1. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined — a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36:959-969. Abstract

Amal Mattu, MD, FAAEM, FACEP, Associate Professor of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Program Director, Emergency Medicine Residency, University of Maryland Medical Center, Baltimore
Disclosure: Amal Mattu, MD, FAAEM, FACEP, has disclosed no relevant financial relationships.


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