Author + information
- Richard Body, MB, ChB, PhD⁎ (, )
- Simon Carley, MD,
- Garry McDowell, PhD,
- Allan S. Jaffe, MD,
- Michael France, MB BS,
- Kennedy Cruickshank, MB, MD,
- Christopher Wibberley, PhD and
- Kevin Mackway-Jones, BM, BCh, MA
- ↵⁎Cardiovascular Sciences, 3rd Floor, Core Technology Facility, University of Manchester, 46 Grafton Street, Manchester, M13 9WL, United Kingdom
We thank Drs. Kavsak and Worster and Drs. Correia and Noya-Rabelo for their interest in our paper (1). We understand the concerns of Drs. Correia and Noya about the specificity of our proposed use of high-sensitivity cardiac troponin T (hs-cTnT) (1). This approach may have more in common with the use of brain natriuretic peptide than D-dimer. Some levels of brain natriuretic peptide are diagnostic of either the presence of heart failure or its absence (2). Other patients have levels that are not sufficiently high or low enough to be diagnostic and require additional testing. This is the case with hs-cTnT. Some patients will have acute myocardial infarction (AMI) ruled out immediately, whereas others still require serial testing to establish a diagnosis, as per current practice (Fig. 1).This will maintain overall specificity while avoiding serial testing in a large group, reducing emergency department crowding and its negative consequences while facilitating accurate patient evaluation and care.
Not all patients with an initial hs-cTnT <3 ng/l will be eligible for early discharge. We strongly believe that hs-cTnT is an adjunct to care and not a substitute for clinical evaluation. For example, 22 (11.3%) of the patients with hs-cTnT <3 ng/l had ischemic electrocardiogram changes. Physicians are unlikely to immediately discharge that group. However, our findings suggest that AMI remains extremely unlikely and alternative diagnoses can be considered at an early stage.
Drs. Kavsak and Worster question the diagnostic performance of hs-cTnT using the limit of detection (LoD) (5 ng/l) rather than the limit of blank (LoB) (3 ng/l) as a cutoff. At the LoD cutoff, 272 (38.7%) patients would have had AMI immediately “ruled out” in our prospective cohort study. Three AMIs would have been missed. Thus, sensitivity fell to 97.7% (95% confidence interval [CI]: 93.4% to 99.5%) with a negative predictive value of 98.9% (95% CI: 96.8% to 99.8%). In our subsequent evaluation of hs-cTnT in clinical practice, 195 (21.3%) patients had an initial hs-cTnT below the LoD and only 2 developed elevated levels (>14 ng/l) on subsequent testing. Thus, sensitivity was 99.7% (95% CI: 98.8% to 100.0%) with negative predictive value 99.0% (95% CI: 96.3% to 99.9%). It remains to be decided whether these results can be confirmed in other datasets and whether the clinical community will find these results acceptable.
Recently, there has been discussion about reporting only down to the LoD rather than to the LoB. Our findings may influence that discussion. If the LoB provides important clinical data, this fact should be considered. Indeed, we reported a sensitivity of 100.0% at the LoB in our cohort study (Reichlin et al.  and, more recently, Christ et al.  also reported the same sensitivity) and a 99.8% value in a cohort from clinical practice. Our findings certainly suggest that further work is necessary to improve the analytical precision of troponin assays at that level.
In our cohort study, samples were not repeated when hemolysis was present, although we understand that hemolysis can lower hs-cTnT levels (4). Fifty-four (7.7%) of the samples in our cohort study showed some degree of hemolysis. Twelve of those samples had values <3 ng/l, which is below the LoB. We would advocate repeating the sample before excluding AMI at any cutoff whether it be the LoB or the LoD. No AMIs were missed using this approach, although the number of patients affected was small.
Our findings are preliminary. They require further prospective validation and subsequent evaluation in a randomized controlled trial. However, approaches like these are required to move the field forward by reducing the time taken to exclude AMI. We believe that we should, over time, be able to unencumber emergency departments by developing innovative approaches for ruling out AMI. Our investigation starts that important work.
- American College of Cardiology Foundation
- Body R.,
- Carley S.,
- McDowell G.,
- et al.
- Dickstein K.,
- Cohen-Solal A.,
- Filippatos G.,
- et al.,
- ESC Committee for Practice Guidelines