Troponin use has rapidly evolved ever since the release of the first commercially available assay in 1997. Testing for the protein was originally performed only for the diagnosis of acute myocardial infarction (AMI), but now, with the advances in technology, the assay has assumed broader application in areas such as risk stratification and prognosis of patients with acute coronary syndromes. Over the years there have also been a number of changes that have helped the medical community better understand myocardial infarction (MI). Specifically, advances in precise imaging techniques have allowed clinicians to detect very small zones of myocardial necrosis. These small zones of necrosis are indicative of myocardial damage and can release small amounts of troponin into circulation. With the availability of more specific information, there have been modifications to the definition of a “positive troponin” and even myocardial infarction.

World Health Organization’s (WHO) Original Definition of MI

The term myocardial infarction is generally used when myocardial necrosis due to myocardial ischemia is evidenced in a clinical setting. Published in 1971, WHO criteria for the identification of MI recommended that the condition can be diagnosed if any two of the following three features are present:

• Symptoms of myocardial ischemia (continuous chest pain for 20 minutes)
• ECG changes with ST segment elevation or Q wave development
• Elevation of sensitive and specific cardiac enzymes in circulation¹

New Universal Definition of MI

With advances in imaging techniques and the availability of more sensitive and specific cardiac biomarkers such as troponin, the joint committee of the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) convened a consensus conference in 1999 to re-examine the definition of MI. The joint committee recommended the following new universal definition of MI in 2000:

• The term myocardial infarction should be used when there is evidence of myocardial necrosis in a clinical setting consistent with of myocardial ischemia.

     Under these conditions, any of the following meets the diagnosis for

     myocardial infarction:

       - Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with

         at least  one value above the 99th percentile of the upper reference limit

         (URL) together with evidence of myocardial ischemia with one of the following:

             - Symptoms of ischemia

             - ECG changes indicative of new ischemia

             - Development of pathological Q waves

             - Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality²

Under the new definition of MI, the joint committee stipulated that troponin was the biomarker of choice for diagnosing MI and that troponin assays used in diagnosis meet the following performance criteria:

Troponin assays should have acceptable precision at the 99th percentile (≤10% of coefficient of variation).

Troponin Assays Following the Redefinition of MI

At the time of the ESC/ACC publication redefining MI, none of the troponin assays in the market met the specified guideline for precision at the 99th percentile. Most troponin assays had a 20-35% CV at the critical decision point.

These new guidelines show less focus on separate decision limits for AMI, but more focus on early detection of myocardial injury along with symptoms of ischemia. This change in practice within the clinical community resulted in a similar shift in laboratory guidelines as represented by the National Academy of Clinical Biochemistry (NACB).
 

Troponin for Risk Stratification

The concept of risk stratification was introduced in the early 1990s, and was based on serial testing over the first 24 hours after the onset of chest pain or admission to the hospital. It helped in estimating an individual’s probability of suffering a major cardiac event in the ensuing 30-60 days, and was applicable only for patients diagnosed with unstable angina, non-ST segment elevation MI (NSTEMI) or chest pain.
 

National Academy of Clinical Biochemistry (NACB) Guidelines

The NACB released their “Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers” consensus statement in the late 1990s, which suggested the following:

• using a specific cardiac marker such as cardiac troponin-I for detecting any myocardial injury and incorporation of a low abnormal decision limit for the optimum use of such markers in ACS patients
• a lower decision limit or cutpoint for cardiac assays, guided by the 97.5th percentile among healthy individuals³