Clinical research study
Using High-sensitivity Troponin T: The Importance of the Proper Gold Standard

https://doi.org/10.1016/j.amjmed.2013.03.003Get rights and content

Abstract

Objective

The study objective was to determine how best to use high-sensitivity cardiac troponin T (hscTnT) to diagnose myocardial infarction.

Methods

A total of 358 patients presenting with acute coronary syndromes sampled at admission and 2, 4, and 6 to 8 hours. Both contemporary cardiac troponin T (cTnT) and hscTnT were measured. Patients were classified with conventional cTnT values by independent investigators. Myocardial infarction required a cTnT value ≥99th reference percentile and a ≥20% change.

Results

Seventy-nine patients had non-ST-segment elevation myocardial infarction, 105 patients had unstable angina, and 174 patients had nonacute coronary syndromes. A cTnT cutoff at the 10% coefficient of variation value missed 14.5% of infarctions. hscTnT had a sensitivity at admission of 89.9%, but specificity was only 75.1% because of elevations in 45.3% and 25.3% of those with unstable angina and nonacute coronary syndromes, respectively. The optimal value for myocardial infarction diagnosis with hscTnT was 25 ng/L at admission and 30 ng/L during serial sampling. All infarctions were diagnosed within 4 hours, with a time saving of 11 and 68 minutes compared with a cTnT value at the 99th reference percentile value and a cTnT value at a coefficient of variation of 10%. By using the 99th percentile of hsTnT plus a ≥20% change, 25 additional infarctions were identified. With these included, the optimal cutoff decreased to 12 ng/L at admission and 13 ng/L over time, but time to diagnosis increased.

Conclusions

The gold standard used to diagnose myocardial infarction makes a major difference in the results. When myocardial infarction is diagnosed using hscTnT 99th percentile values with a 20% change, more are identified, diagnosis is delayed, and the optimal value for use is reduced.

Section snippets

Patients and Samples

TUSCA was a prospective multicenter trial involving 5 emergency departments. It enrolled 358 patients with acute coronary syndromes. To minimize selection bias, single physicians enrolled patients after discussions concerning inclusion criteria. Consecutive patients were included if they were aged >18 years, gave a history of ≥5 minutes of symptoms, and signed informed consent. Exclusion criteria included ST-segment elevation, new left bundle branch block, pre-admission thrombolytic therapy,

Patients

Of the 358 study patients, non-ST-segment elevation myocardial infarction was diagnosed by central adjudication in 79 (22.1%) (Table 1). Unstable angina and nonacute coronary syndromes were diagnosed in 105 patients (29.3%) and 174 patients (48.6%), respectively. Time from onset of symptoms to presentation was available in 88% of patients; 42 patients with myocardial infarction presented within 3 hours of symptoms. A mean of 3.7 samples per patient was obtained; patients lacking all 4 samples

Discussion

These data elucidate important issues concerning the use of hscTnT to diagnose myocardial infarction. Previous reports often relied on cTnT as the gold standard. Our data now document how markedly this alters analyses. The less sensitive gold standard identifies larger infarctions23 and thus exaggerates the benefits of the hscTnT assay. When cTnTCV is used as the gold standard,17,3 it further exaggerates differences, and 14% of acute myocardial infarctions detected using cTnT99 are missed. A

Conclusions

These data provide information about how to use the hscTnT assay to diagnose myocardial infarction. Performance is optimized by using the assay as its own gold standard. Doing so changes the optimal criteria for ruling, the rapidity of diagnosis, the magnitude of the change in values needed for diagnosis, and the specificity of diagnosis while diagnosing additional patients with myocardial infarction.

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  • Cited by (0)

    Funding: Roche Diagnostics Spain provided reagents for and supported the logistics but was not involved in the analyses.

    Conflict of Interest: MS has received honoraria as speaker from Roche Diagnostics. ASJ acknowledges that he does consult or has consulted for most of the major diagnostic companies. JO-L declares that he has received significant financial support for research and honoraria for consultation from Abbott Diagnostics, Alere, and Roche Diagnostics. None of the other authors have any conflicts of interest associated with the work presented in this manuscript.

    Authorship: All authors had access to the data and played a role in writing this manuscript.

    ASJ and JO-L co-directed the work.

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