Studies Provide More Support for High-Sensitivity Troponin Testing to Speed Triage of Patients With Suspected ACS

Using high-sensitivity cardiac troponin I assays—which are not available in the United States—with low cutoffs seems to rapidly and safely rule out or diagnose MI in patients presenting to the emergency department with suspected cardiac chest pain, two new studies suggest.

In the first study, reported by Johannes Tobias Neumann, MD (University Medical Center Hamburg-Eppendorf, Hamburg, Germany), and colleagues, a 1-hour, rule-out algorithm provided a high negative predictive value (NPV) of 99.8% for NSTEMI type 1 when a cutoff of 6 ng/L—well below the typically used 99th percentile of 27 ng/L—was used.Studies Provide More Support for High-Sensitivity Troponin Testing to Speed Triage of Patients With Suspected ACS

And in the second, reported by Edward Carlton, PhD (North Bristol National Health Service Trust, Bristol, England), and colleagues, combining a single troponin measurement at presentation with a cutoff of 1.2 ng/L—the lower limit of detection—and a nonischemic electrocardiogram (ECG) yielded an NPV of 99.5% and a sensitivity of 99.0%.

Together with prior research, the two studies—published online June 1, 2016, ahead of print in JAMA Cardiology—“lend strong support to the notion that accelerated diagnostic protocols that incorporate [high-sensitivity cardiac troponin assays] can facilitate earlier triage while maintaining an acceptable NPV,” David Morrow, MD (Brigham and Women’s Hospital, Boston, MA), writes in an accompanying editorial.

He adds, however, that “despite many strengths of the available evidence, there are some reasons that these data may overstate the diagnostic performance of rapid strategies to exclude acute coronary syndromes.

“There is a need for additional studies performed in diverse healthcare settings, including in the United States, to add to the robustness of the estimated NPV across a variety of populations,” he continues. “At present, because [high-sensitivity troponin] assays are not available in the United States, serial testing at presentation and 3 to 6 hours with a contemporary sensitive assay remains the US standard of care.”

Accumulating data suggest that that interval can be reduced to 1 to 2 hours without sacrificing the high negative predictive value, Morrow notes. In response, the latest European guidelines for NSTE ACS, which recommend a standard approach using high-sensitivity troponin testing on admission and after 3 hours, also advise “that, if [a high-sensitivity troponin] assay with a validated 0-hour and 1-hour algorithm is available, testing at presentation and 1 hour, together with the absence of high-risk clinical features, is an alternative to testing at 0 hours and 3 hours.”

Ruling Out MI in an Hour

The study by Neumann et al—which was presented at the European Society of Cardiology Congress last year—was a prospective study including 1,040 patients presenting with acute chest pain and/or other symptoms suggestive of acute MI between July 19, 2013, and December 31, 2014.

The primary diagnosis of acute MI was made based on current guidelines using a high-sensitivity troponin T assay (Elecsys; Roche Diagnostics), whereas the 1-hour protocol tested in the study employed the Architect i2000SR high-sensitivity troponin I assay (Abbott Diagnostics).

Using a cutoff value of 6 ng/L, a 1-hour, rule-out algorithm resulted in only one false-negative finding for NSTEMI type 1; the NPV was 99.8%. That approach was comparable to a standard 3-hour approach, which had a 100% NPV. Both the 1- and 3-hour algorithms were superior to using a single troponin measurement at admission.

Mortality through 1 year of follow-up was only 1.0% in the patients with NSTEMI ruled out by the 1-hour protocol, which was significantly lower than the 6.7% rate seen in patients diagnosed with NSTEMI and the 8.2% rate observed in patients in whom MI could not be diagnosed or ruled out.

The performance of the 1-hour protocol using the 6-ng/L cutoff was replicated in two independent cohorts of patients from the ADAPT and APACE studies.

“The 1-hour approach does not yet integrate any clinical measurement such as electrocardiography, which will further increase the safety of this rule-out strategy,” the authors note.

Admission Testing Only

The study by Carlton et al included a total of 3,155 patients recruited between November 1, 2007, and August 10, 2013, for inclusion in five prospective cohort studies: three from England and one each from Australia and New Zealand. The patients had suspected cardiac chest pain and nonischemic ECG findings. Troponin was measured using the Architect Stat high-sensitivity troponin I assay (Abbott Diagnostics).

Using a cutoff of 1.2 ng/L—the lower limit of detection for the assay—acute MI was ruled out via a single measurement at presentation with 99.0% sensitivity and an NPV of 99.5%. Overall, 18.8% of patients had levels below the cutoff, representing potential candidates for early discharge.

Using higher rounded cutoff values up to and including 5 ng/dL yielded sensitivities of less than 98.0%, indicating that “rounded cutoff values above the limit of detection may not have the required sensitivity for clinical implementation,” the authors write, adding that 99.0% is considered the minimum clinically acceptable threshold.

They note that no patients were actually discharged based on the admission measurement and that further cardiac testing was high across all of the included cohorts. “Therefore,” they say, “whether the strategies tested can be successfully implemented into clinical practice and what further testing is required remains unknown.”

‘Extremely Valuable’ Addition

Commenting for TCTMD, Allan Jaffe, MD (Mayo Clinic, Rochester, MN), said “these and other studies begin to show the tremendous promise” of high-sensitivity assays. “I really think it’s a good thing that these things are being published and they’re being published in the United States, and hopefully they will blunt some of the concerns that some of our colleagues have had about this,” he added, noting that some clinicians are worried about how they would sort through all of the added information derived from the assays.

Although data are accumulating on the utility of high-sensitivity troponin assays, Jaffe said, there are some issues with research in this area that need to be considered. Those include variation in the quality of patient follow-up, choice of the gold standard against which high-sensitivity assays are compared, uncertainty about whether men and women require different cutoffs, and questions about how to handle patients who present early after the onset of symptoms.

But in general, Jaffe said he is positive when it comes to the use of high-sensitivity troponin assays. “I think it’ll be extremely valuable when and if it’s approved in the United States for use,” he said.




  • Neumann JT, Sörensen NA, Schwemer T, et al. Diagnosis of myocardial infarction using a high-sensitivity troponin I 1-hour algorithm. JAMA Cardiol. 2016;Epub ahead of print.
  • Carlton E, Greenslade J, Cullen L, et al. Evaluation of high-sensitivity cardiac troponin I levels in patients with suspected acute coronary syndrome. JAMA Cardiol. 2016;Epub ahead of print.
  • Morrow DA. Evidence-based algorithms using high-sensitivity cardiac troponin in the emergency department. JAMA Cardiol. 2016;Epub ahead of print.


Related Stories:

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

Read Full Bio
  • The study by Neumann et al was supported by the German Center of Cardiovascular Research and an unrestricted grant from Abbott Diagnostics (Biomarkers in Acute Cardiac Care [BACC] trial). The ADAPT trial was supported by a grant from the Queensland Emergency Medicine Foundation.
  • The various cohorts in the study by Carlton et al received funding from the Christchurch Heart Institute, the Queensland Emergency Medicine Research Foundation, Abbott, Alere, the Royal College of Emergency Medicine of the United Kingdom, the UK National Institute for Health Research (NIHR), and the NIHR Clinical Research Network.
  • Carlton reports performing research under collaborative agreements with Abbott and Randox Laboratories.
  • Morrow reports receiving grants from Abbott Laboratories, Amgen, AstraZeneca, Daiichi Sankyo/Eli Lilly, diaDexus, Eisai, Gilead, GlaxoSmithKline, Merck, Novartis, and Roche Diagnostics and personal fees from Abbott Laboratories, AstraZeneca, Daiichi Sankyo/Eli Lilly, diaDexus, Gilead, GlaxoSmithKline, Instrumentation Laboratory, Merck, Novartis, Provencio, and Roche Diagnostics.
  • Jaffe reports consulting for multiple US diagnostic companies.
  • Neumann and Westermann report no relevant conflicts of interest.