High-Sensitivity Troponin: Six Lessons and a Reading
High-Sensitivity Troponin: Six Lessons and a Reading
The counterpoint to the excellent sensitivity of hsTn testing is a lower specificity (ability to rule-in MI). Although cardiac troponin is, by definition, completely specific for myocardial injury, it is not specific for the diagnosis of acute MI. This leads to a problem for hsTn where specificity has been reported to be 80–85% in comparison with figures of 97% for earlier generation troponins. This may have considerable impact on the utility of hsTn testing, as higher false-positive rates may lead to unnecessary subsequent invasive investigations, such as angiography. However, these lower specificities are based upon hsTn testing at much earlier time points and under-estimate the specificity of hsTn. In fact, if early hsTn testing is assessed against diagnoses made on the basis of serial hsTn testing, specificity is 92%.
Despite taking these points into account, the lower specificity of hsTn testing remains a limitation in accurately diagnosing MI. To improve this, serial sampling is required – which is in fact necessary to satisfy the agreed criteria for a diagnosis of MI. The Universal Definition requires a change in troponin to be detected, although this has been frequently ignored in clinical practice, perhaps due to unwanted complexity or lack of general understanding of this concept. Sampling hsTn at admission and then a later time point allows calculation of the change between the two samples (known as the 'delta' value). If this is small it is considered to be a product of analytical or biological variation, whereas larger changes represent continuing troponin leak from damaged cells and, hence, suggest MI. In addition to this improved diagnostic accuracy, a proportion of patients will be ruled in as probably having an MI from the earliest sample, accelerating treatment.
The extent of change in troponin levels required to diagnose an MI is recommended by the ESC guidance as over a 20% relative change (in those patients with an elevated initial hsTn). However, this figure of 20% is based on research using older troponin assays, and although it is widely quoted in guidelines, there is evidence that for hsTnT testing in particular an absolute change of 7–9 ng/L provides better discrimination. A universal consensus is required for the use of delta values before wider adoption.
2. It Is Not as Specific
The counterpoint to the excellent sensitivity of hsTn testing is a lower specificity (ability to rule-in MI). Although cardiac troponin is, by definition, completely specific for myocardial injury, it is not specific for the diagnosis of acute MI. This leads to a problem for hsTn where specificity has been reported to be 80–85% in comparison with figures of 97% for earlier generation troponins. This may have considerable impact on the utility of hsTn testing, as higher false-positive rates may lead to unnecessary subsequent invasive investigations, such as angiography. However, these lower specificities are based upon hsTn testing at much earlier time points and under-estimate the specificity of hsTn. In fact, if early hsTn testing is assessed against diagnoses made on the basis of serial hsTn testing, specificity is 92%.
Despite taking these points into account, the lower specificity of hsTn testing remains a limitation in accurately diagnosing MI. To improve this, serial sampling is required – which is in fact necessary to satisfy the agreed criteria for a diagnosis of MI. The Universal Definition requires a change in troponin to be detected, although this has been frequently ignored in clinical practice, perhaps due to unwanted complexity or lack of general understanding of this concept. Sampling hsTn at admission and then a later time point allows calculation of the change between the two samples (known as the 'delta' value). If this is small it is considered to be a product of analytical or biological variation, whereas larger changes represent continuing troponin leak from damaged cells and, hence, suggest MI. In addition to this improved diagnostic accuracy, a proportion of patients will be ruled in as probably having an MI from the earliest sample, accelerating treatment.
The extent of change in troponin levels required to diagnose an MI is recommended by the ESC guidance as over a 20% relative change (in those patients with an elevated initial hsTn). However, this figure of 20% is based on research using older troponin assays, and although it is widely quoted in guidelines, there is evidence that for hsTnT testing in particular an absolute change of 7–9 ng/L provides better discrimination. A universal consensus is required for the use of delta values before wider adoption.
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