Laboratory medicine as the science that underpins medicine: the “high-sensitivity” troponin paradigm

Abstract

Abstract:The availability of so-called high-sensitivity troponin assays (hsTn) has scored a compelling goal for laboratory medicine, allowing the safe clinical application of international recommendations for the definition of acute myocardial infarction (AMI). However, the introduction of hsTn has not been welcomed by clinicians, claiming an increase in false-positive results. Here we critically trace back the steps following the introduction of hsTn by referring to the 5-year practical experience in our academic hospital and to suitable information available in the literature. In agreement with published data, we found that hsTn introduction was associated with an increased number of AMI diagnoses, whereas the test volume, the revascularization rate, and the proportion of cases with negative angiography findings remained virtually unchanged. Fast-track protocols for ruling out AMI have been further optimized to recommend sampling at presentation and after 3 h only. We focus on a cost-effective use of hsTn that can account for all clinical variables increasing the pre-test probability in order to ensure that tests are ordered only for patients at medium to high risk for acute coronary syndrome (ACS). To guide interpretation of results, hsTn typical release patterns suggestive for AMI should be identified by evaluating the significance of concentration changes. hsTn have markedly shortened the time to rule out or rule in AMI and has the potential to improve the prognostic assessment of critical patients in clinical contexts different from ACS.

Fast track protocols using highly sensitive troponin assays for ruling out and ruling in non-ST elevation acute coronary syndrome

“…The improved sensitivity of hsTn has reinforced the evidence that the 99th percentile decision limit, if applied to only one result, is not functional to the diagnosis of acute myocardial infarction (AMI) and only serial testing allows for the discrimination of acute from chronic pathophysiological mechanisms of troponin release. This is supported by the evidence of high interindividual biological variability of cardiac troponin, jeopardising the clinical application of any fixed cut-off value, as well as by the proof of a wide disagreement between hsTn methods to identify patients above the 99th percentile cut-off [2][3][4]. Sound evidence currently fosters to characterise temporal patterns describing hsTn variation between consecutive samples in one patient, with the final aim to dichotomise typical/atypical hsTn curves according to the magnitude of troponin changes and characterise patterns typical for acute myocardial necrosis [2].…”

“…This is supported by the evidence of high interindividual biological variability of cardiac troponin, jeopardising the clinical application of any fixed cut-off value, as well as by the proof of a wide disagreement between hsTn methods to identify patients above the 99th percentile cut-off [2][3][4]. Sound evidence currently fosters to characterise temporal patterns describing hsTn variation between consecutive samples in one patient, with the final aim to dichotomise typical/atypical hsTn curves according to the magnitude of troponin changes and characterise patterns typical for acute myocardial necrosis [2]. A recent international survey has however, shown a wide misfit between the application of serial testing approach, performed in 70% of audited laboratories, and the definition of a significant hsTn trend (i.e.…”

“…Moving from the conventional troponin assays to hsTn has entailed to detect a typical increase within 3 h from admission with a 100% sensitivity for NSTEMI diagnosis and a net diagnostic gain of 3-9 h [2,8]. Notably, in an ad hoc study the diagnostic anticipation associated to the 0-3 h hsTn testing protocol resulted in a cost for total qualityadjusted life years gained ~4-fold lower than that related to delayed (10 h) testing protocol using conventional troponin assay [9].…”

“…Consequently, serial hsTn sampling may not be required for prediction of NSTEMI diagnosis in chest pain patients with markedly abnormal concentrations at presentation. Integrating this information in the originally proposed rapid algorithm [2] may therefore further improve its performance (Figure 2). …”

“…In spite of the 2014 NICE guidance, the hsTn availability has often not been welcomed by clinicians, claiming an increase in false-positive results, and it is now clear that the hsTn introduction requires changes to diagnostic rules and algorithms [2]. The improved sensitivity of hsTn has reinforced the evidence that the 99th percentile decision limit, if applied to only one result, is not functional to the diagnosis of acute myocardial infarction (AMI) and only serial testing allows for the discrimination of acute from chronic pathophysiological mechanisms of troponin release.…”