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Use of troponins in clinical practice: Evidence against the use of troponins in clinical practice
  1. Mark Mariathas1,2,
  2. Nick Curzen1,2
  1. 1 Wessex Cardiac Unit, University Hospital Southampton NHS F Trust, Southampton, UK
  2. 2 Faculty of Medicine, University of Southampton, Southampton, UK
  1. Correspondence to Professor Nick Curzen, Wessex Cardiac Unit, University Hospital Southampton NHS F Trust, Southampton SO16 6YD, UK; nick.curzen{at}uhs.nhs.uk

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We have read with interest the paper by Collinson et al,1 and we are grateful for an opportunity to respond to their comments, especially those that relate to our recent BMJ paper describing the Is the current threshold for diagnosing raised highly sensitive troponin apparopriate for a hospital population? (CHARIOT) study.2

The use of more sensitive troponin assays in UK hospitals is now universal. The frontline clinical staff who request and then interpret the test belong to a wide range of clinical specialties. The concept for CHARIOT emerged out of our observations that there was an important mismatch in actual clinical practice between the extremely precise guidelines that lay out how these assays should be employed to rule out myocardial infarction (MI), or diagnose MI or myocardial injury, and their actual use. Specifically, there are important and widespread misconceptions about how troponin values should be or can be interpreted. First, that the manufacturer-provided 99th centile value for their assay represents a binary ‘upper limit of normal’ for a hospital population. Second, that a single troponin result above that 99th centile represents an ‘acute coronary syndrome’ diagnosis, regardless of whether there is an appropriate accompanying history. Third, that the general awareness that type 2 MI and myocardial injury are common, distinct clinical entities from type 1 MI, both pathophysiologically and in terms of appropriate management algorithms, and with potentially even worse prognosis, is low at the front line. This is neatly illustrated, for example, by the low rate of diagnosis of type 2 MI in one series from our group.3

The implications of such misconceptions are that, at best, staff could be requesting the test for the wrong reason, but, at worst, that some patients could be misdiagnosed with, and even treated for, type 1 MI. These misconceptions about the more sensitive troponin assays in current UK practice and their potential clinical implications are likely to be pertinent to any such assay, whether classified as a truly highly sensitive or not.

It was in response to these concerns that we sought to assess what the distribution of troponin values was in 20 000 consecutive patients attending our hospital who needed a blood test for any indication. It was our specific expectation that if CHARIOT were to demonstrate that the distribution in the whole hospital population (as determined by the 99th centile) was different from the 99th centile derived from a healthy population by the manufacturer, it would raise awareness among frontline clinical colleagues that the reflex use of the lab ‘cut-off’ is associated with important flaws. The result of our study indeed highlighted this point very clearly and therefore our work succeeded in its primary objective. The educational value of the work is therefore high, particularly as it has sparked debate about the appropriateness of the widespread use of the troponin assays in inpatients without any history of chest pain.

Above and beyond this explanation for what we set out to achieve in CHARIOT, which does not seem to be well understood by them, Collinson et al 1 have raised some specific criticisms of the study. To begin, CHARIOT employed the troponin assay that was being used clinically in our Trust at the time it was conceived and executed. We accept that there is a difference between this assay and a modern assay defined as truly ‘highly sensitive’, but the assay in the study was indeed installed as a higher sensitivity test at that time. Importantly, whether labelled as a ‘contemporary assay’ or ‘high sensitivity’ makes no difference to the underlying hypothesis or its conclusions because these are based on the way the assay was being used and interpreted. The same applies to the esoteric considerations about the limit of quantification, although we are grateful for the correction, or the (correctly defined) quoted units that are used at our centre. Further, for the sake of accuracy, the study population included outpatients and inpatients, not just ‘admissions’ as stated by Collinson et al’ 1. Finally, existing data regarding the predictive value of cardiac troponin (cTn) for clinical outcomes in intensive care settings are actually discrepant, as highlighted in our recent literature review.4

We specifically defend our use of the term ‘true’ 99th distribution to describe our results since this was precisely our stated primary aim. The implication of our data is exactly counter, in our view, to the criticism that we should not imply that the 99th centile provided by the manufacturer for their assay is not in fact the ‘true’ one: because we have proven our hypothesis that this is indeed not the ‘true’ 99th centile for all comers at a hospital, despite the fact that in the vast majority there was no clinical suspicion of MI or myocardial injury. This neatly and emphatically illustrates to frontline clinical colleagues why a single ‘raised’ troponin level (regardless of assay) does not automatically mean type 1 MI. We, too, advocate using the guidelines for the diagnosis of type 1 MI, and we believe that our work has helped to raise awareness about the potential flaws of using the assay without a full understanding of the contemporary classification of MI. Collinson et al 1 must surely accept that our data do raise important questions about the application of the manufacturer’s 99th centile to a hospital population?

We agree that high-sensitivity-cTn assays have recently been shown both to detect underlying cardiac disease and to predict future events in populations with chronic disease, whether ostensibly cardiac or not. In fact, this was exactly the basis for our recent commentary in the Lancet.5 However, such theoretical concepts represent potential exciting future uses of these assays, but do not yet reflect the way that they are most commonly used and interpreted in the front line today.

In summary, our work has highlighted for frontline staff that there is more to the use and interpretation of a troponin test than that the result is above the manufacturer’s 99th centile, commonly used in practice as an ‘upper limit of normal’. We, too, advocate improving education and awareness for frontline staff about the Universal Definition of MI, and especially the differences between type 1 MI and type 2 or myocardial injury. We agree that the troponin tests currently available should be used routinely to robustly rule out MI, but, given our results, we call into question whether using troponin assays outside this clinical context is of real clinical value in most cases, particularly outside the context of a history of cardiac chest pain?

References

Footnotes

  • Twitter @NickCurzen

  • Contributors This article was drafted by both listed authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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