First Point-of-Care hs-Troponin I Assay Matches Lab-Based Tests

The assay, TriageTrue, provides a NPV of 100% when used in a 0/1-hour algorithm, APACE researchers found.

First Point-of-Care hs-Troponin I Assay Matches Lab-Based Tests

In patients with suspected MI, a high-sensitivity troponin I (hs-cTnI) assay that can be done at the point of care (POC)—with rapid turnaround—offers similarly high diagnostic accuracy for non-ST-segment myocardial infarction compared to assays requiring a central lab, data from the APACE study show.

Moreover, the TriageTrue POC hs-cTnI assay (Quidel) performed well when employed in the 0/1-hour algorithm strategy endorsed by the European Society of Cardiology, Jasper Boeddinghaus, MD (University Hospital Basel, Switzerland), and colleagues report in their paper published online yesterday in the Journal of the American College of Cardiology.

TriageTrue received CE Mark in late 2018 but has not yet been approved by the US Food and Drug Administration. The test is performed using the long-approved Triage MeterPro system (Quidel).

Boeddinghaus told TCTMD that the POC test can produce results within 15 minutes, whereas lab-based tests may take up to 60 minutes. “Besides allowing an earlier triage decision, POC hs-cTnI testing could be used in smaller hospitals without central laboratories on-site. Additionally, the POC assay could be used in private practices or the ambulance to initially evaluate the patient’s risk for an MI and to decide whether an immediate transport (eg, to a heart center) is indicated,” he wrote via email.

The existence of a POC option for high-sensitivity troponin is big news, James Januzzi Jr, MD (Massachusetts General Hospital, Boston), commented to TCTMD.

“These data are robust first and foremost but [also] are from a platform that people have a great deal of experience with. [Triage MeterPro] is a well-recognized device with a substantial amount of market penetration already,” he said. “What this means is that once they get regulatory approval this can be a widely available and widely applied test, which is I think good for patients and good for clinicians.”

For Januzzi, a strength of the paper is its comparison of TriageTrue to not one but two widely used lab-based tests. The researchers also “examined how the assay would perform within the context of a 0- and 1-hour accelerated diagnostic protocol,” he noted. “So they’ve really provided a roadmap for how the test might be used in clinical practice and essentially a pathway for regulatory approval.”

They’ve really provided a roadmap for how the test might be used in clinical practice and essentially a pathway for regulatory approval. James Januzzi Jr

Morton Kern, MD (University of California, Irvine, and VA Long Beach Healthcare System), said what’s striking is that the APACE researchers demonstrated a negative predictive value (NPV) of 100%. “Nobody got missed,” he stressed to TCTMD, adding, “That’s powerful.”

Kern, who did not take part in the study, said that if these results hold up, he could see no reason to choose a lab-based high-sensitivity troponin assay over the POC alternative.

APACE

APACE investigators looked at 1,261 patients (median age 60 years, 32% female) who presented to the emergency department (ED) with suspected NSTEMI; 39% did so within 3 hours of symptom onset.

All underwent three tests: the TriageTrue hs-cTnI, the Elecsys 2010 high-sensitivity troponin T (hs-cTnT; Roche Diagnostics). and the Architect Stat hs-cTnI (Abbott Laboratories).

Ultimately, 14% received a final diagnosis of MI. Other diagnoses included unstable angina (9%), cardiac symptoms arising from a cause other than CAD (tachyarrhythmia, Takotsubo syndrome, heart failure, or myocarditis; 17%); noncardiac symptoms (57%); and unknown (4%).

When measured at presentation, the area under the curve (AUC) was 0.95 with TriageTrue, comparable to the 0.94 seen with Elecsys 2020 and better than the 0.92 seen with Architect Stat (P = 0.213 and < 0.001, respectively). The AUC for TriageTrue rose to 0.97 at 1 and 2 hours and to 0.98 at 3 hours.

With TriageTrue, a cutoff concentration of < 3 ng/L identified 45% of patients as being at low risk of MI, with an NPV of 100% and sensitivity of 100%. A cutoff concentration of > 60 ng/L, on the other hand, classified 11% of patients as high risk of MI; here, positive predictive value (PPV) was 76.8% and specificity was 97.1%.

None of the low-risk, rule-out patients experienced NSTEMI within 30 days. In the high-risk, rule-in group, 77% were found to have NSTEMI. The remaining patients, who were triaged to observation, had an NSTEMI rate of 13%.

As noted above, the researchers developed a 0/1-hour algorithm specific to the TriageTrue assay using a derivation cohort. For rule-out, the optimal threshold was hs-cTnI < 4 ng/L at presentation in patients with chest pain onset > 3 hours or hs-cTnI < 3 ng/L within 1 hour for all patients (irrespective of symptom timing). For rule-in, the cutoff was 60 ng/L at presentation or an absolute change 8 ng/L within 1 hour.

In the validation cohort, this algorithm ruled out MI in 55% of patients, with an NPV of 100%, and ruled in MI at a rate of 18%, with a PPV of 76.%. “The high safety of this approach is further highlighted by the fact that both type 1 and type 2 MI were included in this analysis,” the researchers note.

Cumulative event rates at 30 days were 0%, 1.1%, and 1.2% for rule-out, observe, and rule-in patients, respectively. At 2 years, the rates were 1.6%, 10.2%, and 11.4%.

Confirmation Required

High-sensitivity troponin gives earlier answers than traditional tests, typically at the first evaluation in the ED. Being able to do this at the point of care makes it even easier, proponents say.

Europe converted over to mainly using high-sensitivity lab-based troponin tests a decade ago, Januzzi pointed out. It wasn’t until 2017 that the US Food and Drug Administration signed off on the first such option in the United States: the fifth-generation Elecsys Troponin T STAT assay (Roche),

As to what constitutes “high sensitivity,” he explained that it’s “shades of gray,” with some tests coming close to but not quite reaching that bar. The term speaks to not only how precise the assay is (< 10% imprecision at the 99th percentile for a healthy population) but also its ability to detect a measurable troponin value in at least half of healthy individuals.

“The technologies for each of these assays vary. Some may be calibrated and eventually brought to high-sensitivity performance. The fact that this assay in question has achieved [this] at the point of care provides clear evidence that it is possible,” he said, predicting that other tests are likely to follow in TriageTrue’s wake.

Nobody got missed. Morton Kern

Potential obstacles to uptake are that point-of-care tests are more expensive than central-lab tests and require someone—be that a doctor, nurse, or technician—to run the assay. “It’s a little different than just shooting a tube off to the lab, where it can be run on an automated platform without much in the way of personnel getting involved,” he noted.

“Furthermore,” Januzzi continued, “it’s important to emphasize one of the biggest limitations of point-of-care testing is the fact that you may be able to get a troponin within 15 minutes, but what about all the other lab tests that you may need? What about the chest X-ray? What about the basic metabolic panel, et cetera? And so it’s great that we can get a very rapid answer about whether a patient has myocardial injury, and together with a good history and physical and EKG all available rapidly at the bedside we can really largely assess a patient quite nicely. But then the more complex, nuanced approach for understanding the broader medical picture in a patient—that may have to wait until the labs come back from the central lab.”

As to what’s next, Boeddinghaus said prospective trials must address whether POC hs-cTnI assays are superior to lab-based high-sensitivity troponin tests “in terms of length of stay in the ED, time to decision-making, safety, and also cost-effectiveness.”

Paul Collinson, MD (St. George’s University Hospitals NHS Foundation Trust, London, England), writing in an accompanying editorial, says that point-of-care testing “has the potential to deliver significant impact on length of stay and therefore ED throughput if it is integrated within the clinical decision-making process and analytical sensitivity is comparable with that required for rapid rule-out algorithms.”

Based on the results from APACE, “there is therefore now the opportunity, which did not exist before, to combine the benefits of high-sensitivity troponin measurement with the benefits of point-of-care testing,” he says.

These tests, however, are not a solution to ED workflow issues and require infrastructure as well as frameworks for appropriate testing and decision-making, Collinson added, saying “The importance of process to achieve benefit cannot be underestimated.”

Kern, too, observed that details related to who will perform the test, how it will be billed for, and how to ensure quality control must be worked out. “It introduces a new wrinkle to patient flow from the . . . administrative side,” he said.

Sources
Disclosures
  • The study was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Kommission für Technologie und Innovation, the European Union, the Stiftung für Kardiovaskuläre Forschung Basel, the University of Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, Roche, Ortho Clinical Diagnostics, Quidel, Siemens, and Singulex.
  • Boeddinghaus has received research grants from the University of Basel, the University Hospital of Basel and the Division of Internal Medicine, the Swiss Academy of Medical Sciences, and the Gottfried and Julia Bangerter-Rhyner-Foundation as well as speaker honoraria and/or consulting honoraria from Siemens, Roche Diagnostics, Ortho Clinical Diagnostics, and Quidel Corporation.
  • Collinson and Kern report no relevant conflicts of interest.
  • Januzzi reports consulting for and/or doing research with numerous vendors that make troponin assays including Roche Diagnostics, Abbott, and Siemens.

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