Troponin assay and diagnosis of myocardial infarction

The historical standard for diagnosis of myocardial infarction (MI) comprises a clinical syndrome of chest tightness associated with ST elevation on electrocardiogram (ECG). The advent of troponin assay has altered the diagnostic criteria so that since 2007 the diagnosis of acute MI in patients with suspected acute coronary syndromes requires documentation of changing troponin concentrations in the first 24 hours, with at least one value being above the diagnostic threshold (reference). This introduces a new concept of non-ST elevation MI in patients who would formerly have been classified as having unstable angina. The spectrum of acute coronary syndromes thus extends from angina with exercise-induced ischaemia through to MI.

Although high-sensitivity troponin assays have recently enabled the diagnostic threshold to be reduced, new guidance from the biochemistry group of the Global Task Force for the Universal Definition of Myocardial Infarction raises the prospect of further reductions. The guidance recommends that the 99th centile value for plasma troponin is adopted irrespective of assay imprecision, whereas an assay coefficient of variation of 10% or less was mandated previously. In this issue’s Editor’s Research Choice, Mills et al examine the potential clinical impact of this new guidance in a cohort of patients with suspected acute coronary syndromes.

The study’s main finding was that application of the new guidance increased the proportion of patients diagnosed with MI. This was a predictable consequence, but the increase was surprisingly large, with potentially huge implications for management. The authors estimated that application of the guidance would increase the number of patients diagnosed with acute MI in the UK by 42,000 a year. The first question, therefore, is if this increase in clinical load would be rewarded by management decisions that improve patient outcomes. As the authors acknowledge, this cannot be answered directly because the analysis was retrospective, and the high-sensitivity troponin assay threshold of 0.05ng/ml was used to guide diagnostic and management decisions. Moreover, there is no evidence base to draw on, because patients captured by the new low troponin threshold in the 0.012-0.049ng/ml range have not been the subject of treatment trials.

The increased rate of diagnosis of acute MI consequent on the new guidance is also important because the rate of death or recurrent MI at one year increased progressively with troponin concentrations above the 99th centile and was 13% in patients with concentrations in the range 0.012-0.049ng/ml, who, before the new guidance, would have escaped a diagnosis of MI. Thus, the new guidance recommending that the 99th centile value for plasma troponin be adopted as the diagnostic threshold, regardless of assay imprecision, would not only increase the infarct population but would also capture more patients at risk of recurrent events without increasing our ability to identify them.

Mills and colleagues state that the new guidance could increase the number of patients referred for inpatient coronary angiography by 42%, but this may be an overestimate because there is little evidence that routine invasive management would improve prognosis in those troponin-negative patients who would be reclassified as troponin-positive. The potential downside of the new guidance, therefore, is that it will further stimulate the culture of uncritical management responses to troponin positivity, and that many low-risk patients will have little to gain and more to lose from the procedures that they will undergo. 

Reference: Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Circulation 2007;116:2634-2653