How low can we go: high-sensitivity troponin T in patients presenting with chest pain

Abstract

For the last 10–15 years, troponin measurement has played a central role in the diagnosis of acute myocardial infarction (AMI). This has been most recently confirmed in the universal definition of AMI published by the Joint ESC/ACCF/ AHA/WHF Task Force for the Redefinition of Myocardial Infarction in 2007. This definition of AMI requires the detection of a rise and fall of a cardiac biomarker (preferably troponin) above the 99th percentile of a reference population together with evidence of ischaemia (either as clinical symptoms, electrocardiogram changes or imaging evidence showing loss of viable myocardium). The emphasis on the 99th percentile as the cut-off point comes from evidence obtained using older assays where any measurable troponin increase was associated with worse outcomes. In population studies using the troponin T assay, less than 1% of the population had detectable troponin T concentrations, and these were associated with cardiac abnormalities. The first generation of troponin assays were already superior to the old creatine kinase MB assays and the second-generation troponin assays improved diagnostic sensitivity compared with the first generation. However, only recently an assay (Roche troponin T hs assay) has become available that can consistently measure troponin T in about 50–80% of the normal population. Furthermore, this assay provides increased precision at the 99th percentile. While 10% coefficient of variation (CV) was requested by the original working party at the 99th percentile, none of the troponin assays of the time could provide this. More recently we realized that a 10% CV at this concentration is probably not required and it might be reasonable to accept a functional sensitivity similar to the endocrine assays of about 20%. So, what are the real advantages of newer, more sensitive assays for troponin, if not the improved precision at decision cut-off points? These new high-sensitivity assays give us the opportunity to further refine our diagnostic armamentarium and possibly to improve the diagnostic potential of the assay. Apart from the analytical performance of new assays, it is the clinical evaluation that becomes crucial in trying to judge whether these new assays are real advances. In this edition, two studies look at the performance of the new high-sensitivity troponin T assay in patients presenting with chest pain to a teaching hospital in New Zealand and being evaluated for AMI. These timely papers extend previous studies published in 2009. The first article from Aldous et al. investigates the performance of the high-sensitivity troponin T assay for the early detection of AMI. The sample is fairly small (332 patients out of a total number of about 1500 patients presenting to the Emergency Department) and the incidence of AMI is very high (33%). The New Zealand study confirms earlier studies in a European patient population, showing that the highsensitivity troponin T assay is equivalent to secondgeneration troponin I assays and superior to older style (4th generation) troponin T assays in the diagnostic accuracy for AMI. While the high-sensitivity troponin T assay has a somewhat higher sensitivity for AMI at admission, optimal sensitivity is only achieved about 4–6 h after symptom onset. The gold standard for the diagnosis of AMI was based on older style troponin assays in the European studies, while in this present study an improved second-generation troponin I assay was used. As the investigated troponin I assay was very similar to the assay originally used to make the diagnosis, a positive bias towards the conventional troponin I assay in this study is possible. The second study by Aldous et al. adds significant additional information as it investigates patient outcomes over the next two years. The authors followed up 332 patients with suspected acute coronary syndrome that were investigated between November 2006 and April 2007. Over the following two years, future cardiovascular events (MACE – major adverse cardiovascular endpoint – a composite of cardiovascular death, non-fatal myocardial infarction and revascularization) were measured. Sixty-eight patients experienced a MACE between discharge and two years later. Again, the high-sensitivity troponin T assay was better than the fourth-generation troponin T assay as assessed by receiver operating characteristic curve, but was not noticeably different from the secondgeneration troponin I assay. However, additional information could be obtained from the high-sensitivity troponin T assay in the stratification of patients for future risk.With both the high-sensitivity troponin T and the second-generation troponin I assay, patients with troponin concentrations above the 99th percentile had about a 33% risk of a MACE. Interestingly, with the troponin I assay patients with detectable troponin concentrations