Troponin T for Early Rule-Out of Myocardial Infarction
Troponin T for Early Rule-Out of Myocardial Infarction
Objective To investigate whether a high-sensitivity troponin assay, shown to improve early detection of acute myocardial infarction (AMI), permits accelerated rule-in/rule-out of AMI.
Methods Patients who presented to the emergency department within 4 h of the onset of chest pain suggestive of acute coronary syndrome were prospectively recruited from November 2007 to April 2010. Blood samples were taken at 0, 1, 2 and 12–24 h after presentation and were analysed for clinically applied troponin I and for high-sensitivity troponin T (hsTnT). The dynamic change in hsTnT levels between time points was measured. The primary outcome was admission diagnosis of AMI.
Results Of the 385 patients recruited, 82 (21.3%) had AMI. The sensitivity of hsTnT by 2 h was 95.1% (88.7–98.1%), specificity 75.6% (73.8–76.5%), positive predictive value 53.8% (50.2–55.5%) and negative predictive value 98.3% (96.0–99.3%). The sensitivity was not statistically different between peak values at 2 h and 24 h. Adding ECG results reduced the false negative rate to 1.2%. The additional application of ≥20% delta criterion over the 2 h period for 0–2 h samples increased specificity to 92.4% (90.2–94.3%) but reduced sensitivity to 56.1% (48.0–63.2%).
Conclusion hsTnT taken at 0 and 2 h after presentation, together with ECG results, could identify patients suitable for early stress testing with a false negative rate for AMI of 1.2%. Further trials of such an approach are warranted. The specificity of hsTnT for diagnosing AMI could be improved by the use of a delta of ≥20%, but at the cost of major reductions in sensitivity.
The drive to improve the analytical sensitivity of cardiac troponin (cTn) assays for the diagnosis of acute myocardial infarction (AMI) has led to the development of new high-sensitivity assays based on humanised monoclonal antibodies. Recent studies assessing both late generation contemporary and high-sensitivity assays have demonstrated significantly improved sensitivity for the early diagnosis of AMI. Higher sensitivity assays therefore have the potential to change current chest pain assessment pathways, but no formal recommendations to reduce the time interval between baseline and follow-up cTn have been made to date. There is also concern that early measurements of the cTn concentration may be falsely negative in those presenting early because cTn levels may not have risen by the time of sampling.
The current definition of AMI requires a rise and/or fall in the cTn concentration, which helps distinguish acute elevations from chronically raised levels in conditions such as cardiomyopathy, valvular disease and renal dysfunction. Emphasis on the dynamic change in cTn concentrations from baseline to follow-up ('delta') has intensified as more patients with non-ischaemic conditions have elevations when high-sensitivity assays are used. However, the degree to which the cTn concentration must change and the optimum timing over which dynamic changes should be calculated has not been specified. Previous studies have used various delta criteria including ≥10–30% deltas, receiver operating characteristics (ROC) curves to derive optimum percentage changes and standard deviations. The National Academy of Clinical Biochemistry laboratory medicine practice guidelines recommends the use of ≥20% delta (the level exceeding that due to analytical variation at the 99th percentile) for cTn concentrations from elevated baseline values, but the evidence for such a strategy has yet to be confirmed.
The primary aim of this study was to investigate whether early measurements of high-sensitivity troponin T (hsTnT; Roche Diagnostics, Indianapolis, Indiana, USA) could be used in a new accelerated strategy for the diagnosis of AMI in patients presenting within 4 h from symptom onset. The secondary aim was to compare assays of hsTnT and troponin I (TnI; Abbott Diagnostics, Chicago, Illinois, USA), a late generation cTn assay, at matched time points.
Abstract and Introduction
Abstract
Objective To investigate whether a high-sensitivity troponin assay, shown to improve early detection of acute myocardial infarction (AMI), permits accelerated rule-in/rule-out of AMI.
Methods Patients who presented to the emergency department within 4 h of the onset of chest pain suggestive of acute coronary syndrome were prospectively recruited from November 2007 to April 2010. Blood samples were taken at 0, 1, 2 and 12–24 h after presentation and were analysed for clinically applied troponin I and for high-sensitivity troponin T (hsTnT). The dynamic change in hsTnT levels between time points was measured. The primary outcome was admission diagnosis of AMI.
Results Of the 385 patients recruited, 82 (21.3%) had AMI. The sensitivity of hsTnT by 2 h was 95.1% (88.7–98.1%), specificity 75.6% (73.8–76.5%), positive predictive value 53.8% (50.2–55.5%) and negative predictive value 98.3% (96.0–99.3%). The sensitivity was not statistically different between peak values at 2 h and 24 h. Adding ECG results reduced the false negative rate to 1.2%. The additional application of ≥20% delta criterion over the 2 h period for 0–2 h samples increased specificity to 92.4% (90.2–94.3%) but reduced sensitivity to 56.1% (48.0–63.2%).
Conclusion hsTnT taken at 0 and 2 h after presentation, together with ECG results, could identify patients suitable for early stress testing with a false negative rate for AMI of 1.2%. Further trials of such an approach are warranted. The specificity of hsTnT for diagnosing AMI could be improved by the use of a delta of ≥20%, but at the cost of major reductions in sensitivity.
Introduction
The drive to improve the analytical sensitivity of cardiac troponin (cTn) assays for the diagnosis of acute myocardial infarction (AMI) has led to the development of new high-sensitivity assays based on humanised monoclonal antibodies. Recent studies assessing both late generation contemporary and high-sensitivity assays have demonstrated significantly improved sensitivity for the early diagnosis of AMI. Higher sensitivity assays therefore have the potential to change current chest pain assessment pathways, but no formal recommendations to reduce the time interval between baseline and follow-up cTn have been made to date. There is also concern that early measurements of the cTn concentration may be falsely negative in those presenting early because cTn levels may not have risen by the time of sampling.
The current definition of AMI requires a rise and/or fall in the cTn concentration, which helps distinguish acute elevations from chronically raised levels in conditions such as cardiomyopathy, valvular disease and renal dysfunction. Emphasis on the dynamic change in cTn concentrations from baseline to follow-up ('delta') has intensified as more patients with non-ischaemic conditions have elevations when high-sensitivity assays are used. However, the degree to which the cTn concentration must change and the optimum timing over which dynamic changes should be calculated has not been specified. Previous studies have used various delta criteria including ≥10–30% deltas, receiver operating characteristics (ROC) curves to derive optimum percentage changes and standard deviations. The National Academy of Clinical Biochemistry laboratory medicine practice guidelines recommends the use of ≥20% delta (the level exceeding that due to analytical variation at the 99th percentile) for cTn concentrations from elevated baseline values, but the evidence for such a strategy has yet to be confirmed.
The primary aim of this study was to investigate whether early measurements of high-sensitivity troponin T (hsTnT; Roche Diagnostics, Indianapolis, Indiana, USA) could be used in a new accelerated strategy for the diagnosis of AMI in patients presenting within 4 h from symptom onset. The secondary aim was to compare assays of hsTnT and troponin I (TnI; Abbott Diagnostics, Chicago, Illinois, USA), a late generation cTn assay, at matched time points.
