Ischaemic heart disease persists as the world's leading cause of mortality with serious consequences for unrecognised disease.1 Chest pain, the cardinal symptom of acute coronary syndromes (ACS), accounts for over six million adult emergency department (ED) visits in the USA and greater than 360 000 in England and Wales each year.2 ,3 If ACS is diagnosed early, there are effective interventions that improve outcomes. Therefore, increasing our diagnostic accuracy in ACS, specifically for acute myocardial infarctions (AMI), including both ST segment and non-ST segment elevation, is critical. A major part of these efforts is the use of biomarkers, primarily the serum troponin assay. To address the expanding clinical use of different troponin assays, the American College of Cardiology Foundation (ACCF) recently issued guidelines on interpreting troponin assays in the clinical setting.4 It notes several recent studies supporting high-sensitivity troponin (HS-Tn) assays as a mechanism to rapidly rule out AMI. These assays are quickly replacing troponin-I as the standard of care in routine clinical practice.4–8 However, these studies do not address one consequence of increasing sensitivity: the tradeoff of increased positive results in the absence of ACS and their associated patient health and financial costs.

Several studies have demonstrated the ability of HS-Tn assays to rapidly ‘rule out’ AMI in their respective populations when coupled with standard clinical assessment and ECG.4–8 Achieving a ‘rapid rule-out,’ that is, quickly obtaining accurate negative results, is helpful for the process of safely excluding persons without AMI. A perfect test would achieve …