The diagnostic criteria for myocardial infarction (MI) are obtained from the triad of clinical presentation, electrocardiogram (ECG) changes, and serial cardiac enzyme or biomarker measurements. In recent years, the emphasis on biomarkers — specifically, troponin (Tn) — has increased, while ECG findings and clinical symptoms have received relatively little attention. Nonetheless, a detectable Tn level alone does not equal a diagnosis of MI.

TROPONIN AND MYOCARDIAL DAMAGE

Acute coronary syndromes (ACS) is a general term used when clinical symptoms and signs of myocardial ischemia are caused by obstruction of flow through the coronary arteries, and it typically has included both MI and unstable angina. A European Society of Cardiology and American College of Cardiology joint consensus document (published in 2000, updated in 2007) explicitly defines MI as myocardial necrosis secondary to ischemia, which can also occur in ACS without MI. Cardiac Tn is an extremely specific marker of cardiac injury; however, myocardial damage is not specific to either MI or ACS.

Several new high-sensitivity Tn (hsTn) assays are able to detect levels of Tn that would register as zero with older, conventional assays. The advantages of the hsTn assays — greater sensitivity in identifying myocardial injury and potential for earlier detection of MI — come at the cost of a reduction in specificity for the diagnosis of ACS. Indeed, in a recent report, investigators used cardiac computed tomography to confirm a mechanistic association between elevated hsTn levels and myocardial damage, not only in patients with ACS but also in those without ACS. Even with conventional Tn assays, patients can have detectable Tn levels because of etiologies other than ACS; the use of hsTn is likely to increase such false-positive findings.

We need to reassess the currently held belief that Tn is released only from irreversibly injured myocardial cells. In a recent study, marathon runners had significant elevations in Tn levels after a race. The authors postulated two alternative mechanisms for increased Tn values after heavy exertion: true myocardial injury resulting from the breakdown of myocytes, and cytosolic release of the biomarker. In the marathon study, delayed-enhancement cardiac magnetic resonance imaging supported a cytosolic release, and the authors of a recent review concluded that increased membrane permeability is a likelier mechanism than myocardial necrosis for exercise-induced Tn release. Researchers have now determined that hsTn can be detected in healthy populations and that elevated levels are associated with increased cardiovascular risk (Am Heart J 2010; 159:972).

The goal of diagnosing any medical condition is to classify patients by prognosis, pathophysiology, and response to specific therapies. An elevated Tn level in a patient with sepsis, hypertensive emergency, pulmonary embolism, hypotension, renal failure, or any of several other conditions indicates that myocardial damage or even nonthrombotic MI (the extreme end of the spectrum of demand ischemia) has occurred, producing leakage of low levels of Tn and likely indicating a poor prognosis. However, an elevated Tn level does not mean that the patient has ACS, and therefore should not necessarily lead to ACS-directed care. To distinguish ACS from nonocclusive conditions, a compatible clinical syndrome must be accompanied by a change in Tn levels — rising, falling, or both.

CONCLUSION

High-sensitivity assays will enable physicians to both confirm and exclude MI sooner than is now possible, but serial testing at 0, 4, and 8 hours remains necessary. Moreover, the tests are useful for diagnosing (“ruling in”) certain high-risk conditions (demand ischemia and MI) but not for excluding (“ruling out”) the diagnosis of unstable angina — also a high-risk situation for the patient but one in which troponin leak might not occur. Overreliance on Tn and failure to consider ECG findings and clinical presentation appropriately can lead to both over- and underdiagnosis of MI, each of which carries its own set of hazards.

— J. Stephen Bohan, MD, MS, FACP, FACEP, and Joel M. Gore, MD

Published in Journal Watch Emergency Medicine August 5, 2010