Cardiac troponins (cTn) are specific for myocardial damage.¹ cTn measurements have prognostic value² and indicate the response to a range of treatment modalities including low-molecular-weight heparins,³ glycoprotein IIb/IIIa antagonists^4,5 and revascularization.^2,6,7 How should cTn measurement be incorporated into routine clinical practice, and what is the likely impact on the laboratory?

cTns appear to be the “wonder test.” As they become more widely used, confusion has arisen in the minds of some cardiologists and general physicians who equate the presence of an elevated cTn with the diagnosis of acute myocardial infarction, and the absence of cTn with no ischemic heart disease. Unfortunately, this quest for diagnostic certainty is doomed to failure, as AMI remains a clinical diagnosis. This fact is recognized in the recent document of the joint committee of the European Society of Cardiology and American College of Cardiology redefining AMI.⁸ The elevation of cTns also occurs in a range of conditions other than acute coronary syndrome (ACS), varying from the glaringly obvious, such as myocardial trauma (whether from a knife through the heart or the machinations of a cardiothoracic surgeon), through cocaine overdose (causing intense coronary vasoconstriction) to myocarditis. This ambiguity is easily resolved by dividing the causes of cTn elevation into three categories. In primary ischemic cardiac injury (PICI), cTn elevation occurs as a result of a ruptured coronary plaque. Secondary ischemic cardiac injury (SICI) is cardiac injury arising as a result of ischemia not primarily due to a ruptured plaque. Finally, nonischemic cardiac injury (NICI) is injury caused by direct cardiac damage. Examples appear in Table 1.

Table 1. Conditions characterized by cardiac troponin elevation

cTn measurements are useful in three categories of patients designated in the following discussion as STEMI, NSTEMI, and low risk.

STEMI patients
In patients with definite acute myocardial infarction (ST elevation MI), a single cTn measurement taken 12 to 24 hours after admission serves to confirm the diagnosis and indicate the degree of myocardial damage.⁹ The argument is often advanced that ST segment elevation is entirely cardiac specific and therefore biochemistry has no role to play. It has been demonstrated in routine clinical practice, however, that the sensitivity of the ECG, even when there is ST segment elevation, is only 95 percent.¹⁰ Clearly, therefore, biochemical testing is needed for audit. Although studies have demonstrated that admission cTn measurements allow further risk stratification in patients with STEMI, there is currently no known therapeutic approach that can be used to improve outcome in this group. Even when primary angioplasty is used, patients presenting with STEMI who are cTn positive have a worse outcome. For the laboratory, therefore, this means that the provision of a 24-hour cTn service is a prerequisite for managing these patients. Regrettably, only 10 percent of chest pain admissions receive this service.

NSTEMI patients
The recommended management guideline for non-ST elevation patients at high risk of ACS (non-ST elevation myocardial infarction and unstable angina) is covered in a recent European Society of Cardiology publication.¹¹ A pragmatic flowchart appears in Figure 1. This is based on the findings that the response to low-molecular-weight heparins, glycoprotein IIb/IIIa antagonists and revascularization are predicted by cTn status: only patients who are cTn positive respond. The inability of most hospitals in the UK to deliver a clinically appropriate service does modify the demands on the laboratory. An ideal strategy would be to measure cTn on admission, then 4 to 6 hours and 12 hours after admission. This would be followed by treatment with a IIb/IIIa blocker and early intervention in cTn-positive patients. The absence of such facilities in the UK means that a policy based on measurement at 12 hours with subsequent treatment guided by the cTn status at that point is probably all that is currently feasible. The laboratory service to support the ideal approach, based on current equipment, is possible. It does mean, however, that cTn measurement should be available on weekends as well. If a truly treatment-targeted diagnosis were undertaken, a 24-hour service for cTn estimation would be performed. If the strategy were based on upstream treatment with a glycoprotein IIb/IIIa blocker such as tirofiban prior to angioplasty,⁷ then a very rapid service would be required. Ultimately this is likely to require either a laboratory turnaround time of 30 minutes on a 24-hour basis or, more probably, the use of point-of-care testing in selected cases.

Figure 1. Management strategy for patients admitted with high risk for acute cardiac syndrome (ACS).

Low-risk patients
Patients at low risk can be selected on clinical criteria. These are patients without a preexisting history of coronary artery disease or atypical history who have a normal ECG and absence of conventional risk factors. In this group, the instance of missed myocardial infarction is typically on the order of 5 percent,¹² but a strategy based on cTn measurement over 4 to 6 hours after admission would significantly reduce this miss rate. At 4 hours after admission, the diagnostic sensitivity of cTn measurement is 90 percent. Because only 5 percent of this patient group will have an AMI, 90 percent of the group would be detected and the occurrence of missed AMI reduced typically to less than 1 percent. Since, in the very short term, patients with a normal ECG and a normal cTn after 4 hours are at very low risk, this patient group can be investigated by follow-up (next-day) cTn measurement and noninvasive testing via a rapid-access chest pain clinic. A typical testing paradigm is illustrated in Figure 2. It is not reasonable simply to discharge these patients without some form of follow-up, since a small percentage of this population has a cardiac event. Providing this service is more challenging for the laboratory since it requires, effectively, a 24-hour cTn service.

Figure 2. Management strategy for emergency department (ED) rule-out.

Conclusion
In conclusion, cTns have a major role in the management of patients with chest pain, but the service configuration is dominated by the management pathways in place. Without appropriate clinical management pathways to triage patients according to risk group and investigate them accordingly, the frequency and timeliness of laboratory testing is irrelevant. It is up to the laboratory and the clinicians to define their management pathways and the role of biochemical markers within them. It should be remembered that the use of cTns in risk stratification is recognized by European, British and American guidelines and also by the National Institute of Clinical Excellence (UK). The challenge is to deliver the service.

References
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