Adoption of high-sensitivity cardiac troponin (hs-cTn) I or T assays has taken off around the world, most recently in the United States. While much of the knowledge surrounding older assays is transferable, clinicians and laboratorians need to know the differences between conventional cTn and hs-cTn assays before implementing this new technology in clinical practice. Experts empaneled by the Journal of the American College of Cardiology (JACC) and led by associate editor James Januzzi, MD, an esteemed cardiologist and biomarker expert, walk through the concepts that institutions should consider in transitioning to hs-cTn assays.
Their guidance explains why these tests are more sensitive, how they’re classified, and what labs should consider before transitioning to hs-cTn assays. It also discusses troponin’s core conceptions and how different testing methods are deployed and interpreted. “Even within the category of hs-cTnI or T assays, there will be variability in cutoff values, sensitivity, and specificity, as well as in the way in which these tests are interpreted,” wrote the panelists.
Aimed mostly at cardiologists and emergency medicine specialists, the American College of Cardiology (ACC) recognized that this guidance could serve other groups, noted Allan Jaffe, MD, a cardiologist and laboratorian and chair of the division of clinical core laboratory services at Mayo Clinic in Rochester, Minnesota, who co-authored the paper with Robert Christenson, PhD and other colleagues. The group allowed for a more extensive laboratory section to help clinicians understand key analytic concepts and also to expand the guidance’s educational value to laboratory professionals, Jaffe told CLN Stat. A similar tack was taken in the sections on emergency department (ED) evaluation to help ED practices.
“It turns out that the document is useful to many stakeholders in addition to cardiologists, including laboratorians and emergency medicine practitioners,” observed Christenson, professor of pathology and professor of medical and research technology at the University of Maryland School of Medicine in Baltimore. Labs in particular are at the center of this transition, he emphasized. The basic fact with hs-cTn assays is “we are still measuring the same analyte but with far more sensitive assays,” Christenson said. Other points such as the use of different units and the possible use for earlier rule-out algorithms of myocardial infarction (MI) are important items that clinicians and labs need to discuss, he added.
Labs need to appreciate the issues surrounding these assays, and help clinicians understand how to use them, Jaffe advised. Labs also play a role in facilitating rapid turnaround times, avoiding analytical and preanalytical problems, and troubleshooting results that don’t agree with a given clinical situation.
The panelists’ guidance includes an algorithm or series of preparation points for clinical labs to consider when transitioning to hs-cTn tests:
- Is the lab ready to provide necessary analytical education?
- Has an assay been selected?
- Was assay performance acceptable in the local clinical lab?
- Which 99th percentile cutoff will be used?
- Is the lab able to process samples within a reasonable time frame?
- Is the reporting of results integrated well with the electronic health record?
Figuring out which 99th percentile to use “is a particularly dicey issue,” acknowledged Christenson. Discussions with stakeholders and champions need to take place on items such as the use of sex-specific 99th percentiles, he said.
Most companies and local labs don’t do a good job of conducting normal value studies on the 99th percentile, Jaffe observed. For this reason, published literature is often the best way to proceed. “It is no guarantee, but it is probably often as good or better than using the package insert,” he offered. Both experts recommended that labs consult with AACC’s Universal Sample Bank (USB) group to establish a 99th percentile upper reference limit.
“A huge factor identified is heterogeneity in the populations used to establish 99th percentiles. The AACC USB helps establish an important common denominator,” Christenson suggested.
In other recommendations, the panel emphasized the importance of establishing and maintaining turnaround time with hs-cTn tests “so that the enhanced precision of hs-cTn assays can be translated into earlier rule-out and accelerated diagnostic protocols.” When reporting results, labs should use integers instead of fractions. “The larger numerical result is often perturbing to clinicians, but the consensus is that reporting hs-cTn results as integers will be clearer and safer for interpretation,” the panel advised.
The panelists also cautioned against ruling out acute MI with a single blood test. “Although the sensitivity to exclude [acute] MI and the [negative predictive value] are high at the limit of quantitation concentration, a larger body of evidence will be required before a recommendation for the routine use of this cutoff can be endorsed,” they recommended.
Learning about and transitioning to hs-cTn assays takes time, effort, and patience, Jaffe said. It calls for coordination between the lab, cardiologists, the ED, and hospitalists. Identifying local champions and thought leaders will help guide the transition, Christenson said. “Communication is an element of coordination that is particularly important. Folks in the lab need to deliver a consistent message,” he said.