Troponin testing: an audit in three metropolitan hospitals

Assays of the cardiac-specific troponins T and I (cTnT and cTnI) have rapidly become the criterion standard for chemical diagnosis of myocardial damage since they were introduced in the 1990s. These assays are more sensitive and specific than assays of the creatine kinase-MB isoenzyme (CK-MB), which they have largely replaced.1

Interpreting results of troponin assays is easy if levels are at the upper end of the abnormal range, but presents a challenge at the lower end. "Acute coronary syndrome" has been devised as a category for patients with troponin levels of indeterminate significance pending results of further investigations.2

Troponin challenges doctors because its behaviour is similar but not identical to that of CK-MB. Levels of troponin, like CK-MB, do not rise immediately after myocardial damage but take about 6 hours to become diagnostically reliable. However, the kinetics of disappearance of the two substances from the bloodstream differ markedly. CK-MB is rapidly released into the blood in the few hours after infarction, reaches a peak concentration quickly, and then declines with a half-life of about 12 hours. In contrast, troponins continue to be shed into the bloodstream while the damaged myocardium is undergoing repair and are continuously cleared. Consequently, a steady state level of troponin is achieved rapidly after an infarct and often maintained for up to a week, before falling back to pre-infarct levels over little more than a day.3

The diagnostic dilemma is thus clear: although a troponin assay is the new criterion standard for diagnosing a myocardial infarct, it cannot be used either to follow progress after an infarct or, within the week thereafter, to corroborate a clinically suspected extension of the original infarct or to diagnose a new infarct. Nevertheless, authoritative protocols suggest that a troponin level measured at 6 hours after symptom onset, and, if this is negative, again at 12 hours, safely determines whether a patient's symptoms are caused by an acute myocardial infarction (AMI).4,5

Is the troponin assay used appropriately in the diagnostic process when chest pain is encountered? Is it overused? This report describes the introduction of a troponin assay and its subsequent use in three Melbourne hospitals.

Troponin assays were ordered during 351 symptom episodes involving 333 patients (Box 2). A single troponin assay was ordered in 194 symptom episodes (55% of all symptom episodes; range across hospitals, 54%–56%; x2 for all differences, P = 0.71). Thirteen of these 194 single assays (7%) had results diagnostic of an AMI. Five of these 13 were routine tests performed 24 h after coronary artery grafting (four patients) or aortic aneurysm repair (one patient), rather than in response to symptoms.

Serial assays were ordered in 157 symptom episodes (45%). Ordering of these assays appeared to follow the recommended protocol closely at all three hospitals, with mean time between serial assays more than 6 hours.

Sixty-four requests for assays were judged inappropriate (10% of all requests; range, 7%–13%). Medical scientists rejected 31 of these (5% of all requests). More of the inappropriate requests were rejected at Hospital A (18/24) than at Hospitals B and C (4/12 and 9/28, respectively).

Recognised protocols suggest that, in patients presenting with symptoms and signs suggesting AMI, this diagnosis can be excluded by two negative troponin results over about 12 hours after presentation.4,5 However, 93% of the 194 single assay requests gave negative results and, as they were not followed by a second (later) assay, were used in a manner at odds with recognised protocols for excluding AMI. In these cases, doctors may have decided on clinical grounds that a second assay was not required. For example, they may have initially overestimated the probability of a myocardial event and revised that estimate as the patient's symptoms evolved.8

Nonetheless, if doctors exclude recent myocardial damage on the basis of a single negative troponin result, they run the risk of missing an evolving infarct. The specificity of a troponin result rises with the time elapsed since myocardial damage begins; in the earliest hours of an infarct, it is too low to safely rule out the diagnosis. It could be argued that if a patient's symptoms generate sufficient clinical suspicion to justify a troponin assay, then AMI cannot be excluded until a second negative troponin result is obtained after a further 6 hours.

On the other hand, requests for serial assays followed the recommended protocol closely at all three hospitals. Mean times between serial tests were at least 6 hours, as required by the protocol, and stretched up to 8 hours. This prolongation reflects the reality of practice in busy tertiary level hospitals.

Laboratory scientists varied in their policing of the protocol. Those at Hospitals B and C were less likely to reject inappropriate specimens than those at Hospital A. No explanation for this difference is obvious.

Conclusions from this audit are twofold. Firstly, a rational approach was uniformly seen when serial troponin assays were used to diagnose AMI. Our support strategy may have helped produce and sustain this outcome. Initially, the strategy provided information about how to use troponin assays, and delivered it with suitable authority at the time the test was introduced. This information was continually reinforced by comments on reports of results. Continued screening of requests to determine appropriateness is needed to provide this ongoing reinforcement.

A weakness of this study is that it did not assess doctors' practice in the absence of the support strategy, and therefore cannot assess the extent to which the strategy modified practice. However, it would have been clinically and ethically improper to have introduced the assay without a support strategy.

Secondly, the finding that a large proportion of requests for troponin assays were single requests is troublesome. This suggests that some clinicians regard a single troponin assay as a remedy for diagnostic dilemmas. However, this is not necessarily so. We need to determine how patients who have a single troponin assay fare, and to educate their doctors not to use the assay in this fashion.

1: Protocol for use of troponin assays