What is the role of troponin T in the diagnosis and risk stratification of acute coronary syndromes?

A significant proportion of patients presenting to accident and emergency departments complain of chest pain. Early risk stratification is vital with the primary aim being to identify lifethreatening conditions such as acute coronary syndromes (ACS) and ensure their appropriate management, especially since the majority of patients have either non-cardiac chest pain or stable angina and are at low risk.

Standard diagnostic approach
The standard approach to the diagnosis of acute chest pain is to combine features of the clinical history, including cardiac risk factor profile, with electrocardiogaphic features and biochemical markers. The Braunwald classification was initially introduced to allow the identification of patients with unstable angina at different levels of risk. It correlates well with in-hospital event rate and prognosis. Unfortunately symptoms may be difficult to interpret and clinical assessment alone is insufficient for risk
stratification. Many studies have shown that admission 12-lead ECG provides direct prognostic information in patients with ACS. However, as many as 50% of patients ultimately diagnosed as having either unstable angina or myocardial infarction present with either a normal ECG or with minor or non-specific ECG changes only.

Traditionally the biochemical diagnosis of myocardial injury was confirmed by measurements of non-specific enzymes such as CK-MB mass or myoglobin, whose levels may also be elevated after non-cardiac injury. The availability of rapid and accurate bedside assays of cardiac troponin T has transformed the diagnostic process. Troponin T is an essential structural protein of the myocardial sarcomere. It is a highly sensitive and specific marker of myocardial damage that is not detectable in the healthy
state. Troponin T is released within 4–6 hours of injury peaking after 12 to 24 hours. Elevated levels of troponin T reflect even minor myocardial damage and remain detectable for up to 14 days. An elevated troponin T has a predictive value for myocardial ischaemia several times higher than CK-MB mass.

Troponin T as a diagnostic tool
Troponin T can be used both as a diagnostic and a prognostic tool in the Accident and Emergency Department. Repeated troponin assays taken 4–6 hours apart have been used to successfully identify all patients with MI even in the absence of ST elevation.1Individuals who were troponin T negative were shown to be at low short term risk. Troponin T accurately reflects the degree of myocardial necrosis with the overall risk of death following an ACS being directly related to the levels detected. Data from the Fragmin During Instability in Coronary Artery Disease trial (FRISC) demonstrated that patients with the highest levels of troponin T following an ACS carried the highest risk of death and MI, in contrast to those who were troponin T negative who were at low risk.2 A subset from the GUSTO IIa trial had similar findings for non-ST elevation ACS where troponin T positive patients had a much higher risk of death and heart failure than troponin T negative individuals.

Risk stratification
The initial step in risk stratification is an ECG. Patients with acute ST elevation are considered to have an acute MI and require reperfusion therapy according to local protocols. Individuals with ST depression are also at high risk and require admission for further evaluation. The presence of a positive troponin T in this group further confirms them as high risk. In situations where patients present either with a normal ECG or with T wave changes only, the value of a positive troponin T is vital in risk stratification. All patients who are troponin T positive should be considered as high risk, whilst in contrast, a negative troponin T 12 hours or more after the onset of symptoms puts the individual in a low risk group. If the result of a negative troponin T test taken 12 hours or more after the onset of chest pain is taken in conjunction with a pre-discharge exercise test, this further reduces the chance of an inappropriate discharge.4 Figure 20.1 illustrates one possible management algorithm.

Conclusion
Troponin T has a vital role in the triage of patients presenting with chest pain. A positive test identifies high-risk individuals who may benefit from aggressive anti-platelet therapy or early intervention, whilst negative troponin T tests 12 or more hours after the onset of symptoms identify those at low risk who can be considered for early hospital discharge.