High-sensitivity troponin measurements: challenges and opportunities for the laboratory and the clinician

There has been a paradigm shift in the role of the laboratory in both acute and chronic management of cardiovascular disease. Cardiac biomarkers are now central to the diagnosis and management of acute cardiac disease. Measurement of the cardiac troponins, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) became incorporated within the redefinition 1 and then definition of acute myocardial infarction 2 (AMI) and was recognized by the European Society of Cardiology (ESC) as central to the management pathway of suspected acute non-ST elevation myocardial infarction (NSTEMI). 3 The shift to the use of cTnT and cTnI measurement was based on the early demonstration that in patients with a final diagnosis excluding AMI and a presumptive diagnosis of unstable angina, approximately one-third had detectable troponin values, and this detectable troponin was associated with an adverse prognosis. 4,5 Measurement of cardiac troponin was demonstrably superior, both diagnostically and prognostically, but was also considerably (typically 10–50 times) more expensive than measurement of ‘cardiac enzymes’. In order to justify the cost, troponin measurement was ‘sold’ to the cardiology and emergency medicine physicians as the ‘golden ticket’. It was totally cardiac specific, and allowed a diagnosis of AMI to be reliably made and needed only be measured once 10–12 h from onset of chest pain/admission. Troponin measurement was embraced with enthusiasm, and some would say clinical judgement was abandoned. At this time, troponin assays were relatively insensitive, troponin could not be detected in the normal healthy individual, and decision limits were optimized for equivalence with diagnosis based on the original WHO criteria for AMI. Hence, the claims for troponin could, at that point, be justified and the troponin era began. There were arguments about relative differences between assays, although the main argument was about troponin elevation in renal failure. It was an inconvenient truth that both cTnT and cTnI were elevated in renal failure, even with the assays then in use. 6 It was also overlooked that cardiac death, especially cardiac sudden death, is the commonest cause of death in patients with renal failure. 7