Clinicians should be aware that the discordance between high-sensitivity cardiac troponin (hs-cTn) assays is significant enough that management recommendations may change, for example, for a patient assessed for suspected acute coronary syndrome (ACS) in one hospital and transferred to another that uses a different assay, according to a team of international researchers.
When hs-cTn concentrations were measured using the three Food and Drug Administration (FDA)-approved assays, only 37.4% (384 of 1027 samples) of blood samples were classified into the same analytical benchmark category.
“We didn’t expect such low concordance, to be honest, but I have to stress that this first assessment used just one-time blood testing and serial testing is what is more commonly recommended now,” said Júlia Karády, MD, from Massachusetts General Hospital and Harvard Medical School, Boston.
To see if concordance improved with serial testing, the researchers looked at the 242 patients for whom serial samples were available and saw concordance of management recommendations across assays rise to 74.8%.
“We tested the 0/2-hour algorithm and found that the overall agreement almost doubled, so I think that a very important message from our study is that serial testing improves the agreement between the assays in terms of clinical management and patient stratification,” said Karády.
Karády and colleagues published their findings today in the Journal of the American College of Cardiology.
The researchers tested three assays referred to clinically as high-sensitivity assays: Elecsys 2010 platform (Roche Diagnostics); ARCHITECT i2000SR (Abbott Diagnostics); and hsVista (Siemens Diagnostics). All three have received FDA approval, starting with Elecsys in 2017.
The proportion of patients with similar management recommendations differed between the assays for both “rule-out” (87.2%, 73.1%, and 78.5% for Roche, Abbott, and Siemens, respectively) and “observe” (9.5%, 24%, and 17.8%; both P < .001). For the purposes of “rule-in,” no difference was noted (3.3%, 2.9%, and 3.7%).
“It’s important to note that this was a highly selected population of patients with an intermediate likelihood for ACS, not an all-comer population. This group comprises about 20% of the [emergency department] population and actually is the group we struggle with the most, which is hardest to diagnose because it excludes the very low- and very high-risk patients,” said Karády.
The patients included in this study all had suspected ACS and were enrolled in the ROMICAT-I and II trials.
Among 1027 samples from 624 patients (mean age, 52.8 years; 39.4% women), samples were classified as below the limit of detection (<LOD) in 56.3%, 10.4%, and 41.2% (P < .001) by Roche, Abbott, and Siemens, respectively.
The proportion of sample with a troponin measurement between LOD to the 99th percentile also differed significantly between the assays at 36.5%, 83.5%, and 52.6%, respectively (P < .001).
Only the proportion classified >99th percentile did not differ (7.2%, 6.0%, and 6.2%; P = .114).
When the researchers looked at sex-specific difference, no differences were seen in “rule-in” numbers for men, but significant differences were seen for women.
“One possible explanation for this could be differences in the representation of men and women in the various reference populations used to develop the 99th percentile values for these assays,” suggested Karády.
They estimate around 30% to 40% of US centers are currently using high-sensitivity troponin assays and this number is “rapidly rising.”
The diagnostic algorithms developed for use with high-sensitivity assays, such as the 0/2-h algorithm, acknowledge differences in performance characteristics and recommend that assay-specific cut points be used for clinical decision-making rather than relying on generally applicable thresholds.
Joseph S. Alpert, MD, University of Arizona College of Medicine, Tucson, and co-authors of an accompanying editorial said the take-home message here is caveat emptor.
“First, ‘let the buyer (ie, the clinician) beware’ when patients are transferred from one hospital to another, where different hs-cTn assays may be used,” they write. This is particularly true in women and in those with troponin levels in the “observe (gray zone)” clinical management recommendation.
Karády has received grant support from the Fulbright Visiting Researcher Grant and the Rosztoczy Foundation. Allan Jaffe, MD, one of the co-authors of the editorial comment, consults or has consulted for most of the major diagnostic companies, including the manufacturers of the three assays tested in this study. Alpert has disclosed no relevant financial relationships.