Risk Stratification in Patients With Acute Chest Pain Using Three hs-cTn Assays
Editor's Note: Commentary based on Haaf P, Reichlin T, Twerenbold R et al. Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays. Eur Heart J 2013. [Epub Ahead of Print].
Measurement of cardiac Troponin (cTn) has become a mainstay for diagnosis of myocyte necrosis among patients with suspected acute myocardial infarction (AMI).1 There has been an ever increasing emphasis on developing high-sensitivity cTn (hs-cTn) assays, which have allowed for early diagnosis of AMI.2 Though many such hs-cTn assays are now commercially available, the prognostic relevance of elevations in hs-cTn is unknown.
In this study, Haaf and colleagues3 aimed to determine the prognostic value of hs-cTn measurement among patients presenting to the emergency department (ED) with acute chest pain. From the ongoing Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) study, the authors identified 1,117 patients with chest pain who underwent cTn measurements by four different assays – conventional cTnT assay and 3 hs-cTn assays: hs-cTnT by Roche Diagnostics (RD), hs-cTnI by Beckman-Coulter (BC) and hs-cTnI by Siemens (S). Patients were followed up for a two year period with the primary clinical end-point being all-cause mortality.
Overall, there was good correlation between the different hs-cTn assays, while there was a poor correlation with cTnT. The median concentrations of the hs-cTn assays did not significantly differ among those who had a ST-elevation MI (STEMI) vs. those with a non ST-elevation MI (NSTEMI). During the follow up period, there were 82 deaths, with no significant difference in the diagnostic accuracy of the three hs-cTn assays in the first 30 days. However, long-term mortality (730 days) was most accurately predicted by hs-cTnT (Roche Diagnostics) AUC: 0.78, when compared to hs-cTnI BC (AUC: 0.71) hs-cTnI S (AUC: 0.70) and cTnT (AUC: 0.67). There were no difference in accuracy for predicting long-term mortality between the two hs-cTnI assays and cTnT. In addition, the AUC for hs-cTnT was greater than that of both hs-cTnI assays for predicting predicting long-term mortality among patients with and without acute myocardial infarction (AMI). Interestingly, the authors also observed that serial assessment of hs-cTn did not add to the prognostic value of hs-cTn measurement at presentation.
The authors conclude that among patients presenting to the ED with chest pain, hs-cTnT has the greatest accuracy for predicting long-term mortality when compared to hs-cTnI. In addition, serial measurement of hs-cTn did not improve the prognostic accuracy above that provided by the single hs-cTn value determined at presentation.
This study compares the accuracy of the various commercially available hs-cTn assays for risk stratification among 'all-comers' presenting to the ED with chest pain. The use of hs-cTn assays has allowed for early diagnosis of AMI2 and there is a strong association between cTn levels and prognosis.
The results from this large study may help further risk stratify patients with chest pain and early elevations in hs-cTn values and parallels the results previously published from select population subgroups. In this study, hs-cTnT outperformed hs-cTnI assays for prognostication of patients presenting with chest pain. This difference was also observed among the elderly, those with AMI, and renal dysfunction. The reasoning for the differences in the prognostic accuracy of the hs-cTn assays remains to be understood. Biological phenomena, such as fibrin or antibody interference and hemolysis of the blood sample could account for these differences (although most of these types of interferences are uncommon with currently available assay techniques), as could the measurement of different cTn moieties by these test (cTnT vs. cTnI).
This study is unique as the authors were able to demonstrate the prognostic implications of hs-cTnT values below the 99th percentile. The authors speculate (as have others) that that concentration of hs-cTnT within the normal range has prognostic implications as it may represent subclinical myocyte damage. Interestingly, the prognostic value provided by serial measures of hs-cTn was not superior to that of the hs-cTn measurement at the time of presentation. This finding can be especially useful in patients with minor elevations in hs-cTn, as seen in non-coronary cardiac chest pain — myopericarditis, heart failure etc. in whom there is little variability in the cTn levels when checked serially.
The major limitation of this study is that the clinical benefit from the improved prognostic value obtained from hs-cTn assays was not studied. Thus, before any clinical recommendations regarding acute management of these patients can be made the clinical benefit needs to be determined, specifically among patients with non- cardiac chest pain and chest pain of unknown etiology, and those with hs-cTn levels within the normal range. Another important limitation is the small number of events; therefore, the differences have the potential to be a chance finding. Additionally, the result from this study are in contrast to that of prior studies, which have either shown no difference between hs-cTnT and hs-cTnI assays4 or a greater prognostic benefit from the use of hs-cTnI assay.5
In summary, there is little doubt that hs-cTn is the method of choice for diagnosing and risk stratifying patients with AMI, and to determine long term prognosis among those without AMI. However, this biomarker study fails to categorically identify clinically relevant differences between various hs-cTn assays and thus the benefit of using a specific hs-cTn assay among patients without and without acute coronary syndrome needs to be further determined.
- Morrow DA, Cannon CP, Jesse RL et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem 2007;53:552-74.
- Keller T, Zeller T, Peetz D et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009;361:868-77.
- Haaf P, Reichlin T, Twerenbold R et al. Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays. Eur Heart J 2013.
- Lindahl B, Eggers KM, Venge P, James S. Evaluation of four sensitive troponin assays for risk assessment in acute coronary syndromes using a new clinically oriented approach for comparison of assays. Clin Chem Lab Med 2013;51:1859-64.
- Omland T, Pfeffer MA, Solomon SD et al. Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease. J Am Coll Cardiol 2013;61:1240-9.
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