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. 1 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.2 The first generation of troponin assays were already superior to the old creatine kinase MB assays 3 and the second-generation troponin assays improved diagnostic sensitivity compared with the first generation. 4 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. 5,6 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%. 7,8 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.9,10 These timely papers extend previous studies published in 2009. 11,12 The first article from Aldous et al.9 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, 11 showing that the highsensitivity troponin T assay is equivalent to secondgeneration troponin I assays and superior...

Peri-operative troponin monitoring using a prototype high-sensitivity cardiac troponin I (hs-cTnI) assay: comparisons with hs-cTnT and contemporary cTnI assays

“…The ability of high-sensitivity assays to detect troponin at concentrations between the LOD and the 99th centile can offer additional prognostic value and risk stratification compared to less sensitive assays, by identifying patients who are at an intermediate risk of future cardiac events. 5…”

“…The ability of high-sensitivity assays to detect troponin at concentrations between the LOD and the 99th centile can offer additional prognostic value and risk stratification compared to less sensitive assays, by identifying patients who are at an intermediate risk of future cardiac events. 5 Troponin evaluations against the 99th centile and the RCV Unlike the earlier report by Jhanji et al, 6 where inflammatory markers were not evaluated against respective reference ranges, in the current study we considered all troponin measurements against each assay's 99th centile concentration. Such elevations were reported most frequently for the hs-cTnT assay, even prior to surgery, and are likely influenced by the age-and sex-related effects on concentration.…”

“…4 The latest generation of hs-cTnT and cTnI assays now detect concentrations below the 99th centile with acceptable imprecision (CVs of 410%) and can therefore allow sub-clinical monitoring of possible myocardial remodelling and myocyte turnover. hs-cTn assays can also offer improved risk stratification by identifying patients with troponin concentrations greater than the limit of detection (LOD) but <99th centile, who are at an intermediate risk of major adverse cardiac events 5 and for whom intervention may alter risk and improve prognosis.…”

Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: More than just a sensitivity issue

“…The ability to use lower thresholds is directly attributable to the superior imprecision of hs-cTn assays and helps to identify more patients at risk of recurrent MI and death that would otherwise not be detected using the less analytically precise cTnI assay [34] and would be unlikely to be considered as appropriate candidates for cardiology referral or secondary prevention therapies. Furthermore, the analytical improvement which underpins hs-cTn assays also translates into improved risk stratification by permitting reliable identification of patients with myocardial injury, irrespective of the pathophysiology, who have troponin concentrations below the overall 99th percentile but inclusive of the female-specific threshold, and worse prognosis than those with undetectable levels [6] . Since our study did not include a period of follow up, we could not confirm whether or not non-ACS patients with troponin elevations (>99th percentile) and probable myocardial injury had worse outcome than those without elevations.…”

“…During this time analytical developments have also resulted in the emergence of high-sensitivity Troponin (hs-cTn) assays into diagnostic use [2] , [3] which allow earlier detection of myocardial injury and show improved accuracy over established sensitive assays for diagnosis of AMI [4] , [5] . Improved imprecision at concentrations below the 99th percentile of the normal population has permitted measurement of troponin in a greater proportion of healthy individuals [2] and identification of patients with detectable troponin concentrations, less than the 99th percentile, who are at intermediate risk of major adverse cardiac events (MACE) [6] . A possible paradigm shift for troponin use in prognosis, screening and sub-clinical monitoring of myocardial remodelling has therefore emerged [7] , [8] and further emphasises the need for laboratories to fully evaluate this test both analytically and clinically.…”