ED, lab views on point-of-care cardiac troponin

The high-sensitivity POC devices likely will be inexpensive, Dr. Wu says, “so the cost for the instrument has to be taken out of the equation. It’s the cost of the consumables, the calibrations, and the labor, and those are going to be higher for point-of-care [testing], at least analytically.” Real cost savings, he says, may come from changes in emergency department flow.

And those savings come from opening up an ED bed, Dr. Diercks responds. In her ED, which relies on the high-sensitivity troponin performed in the clinical laboratory, “we check a test only once if it’s below the limit of detection” and the patient is low risk by a stratification score like HEART. “Then we can stop testing that patient. That’s only 25 to 30 percent of patients that we see in the emergency department. Everyone else will get serial tests. And in the era of serial testing, the cost savings on throughput just aren’t as great. When you balance the decrease in time of patient stay in the ED” with the analytic and POC laboratory issues Dr. Wu raises, she says, “that makes me fall right in the middle. Maybe it will be cost-effective. We just don’t have enough information to make a statement.”

Does Dr. Diercks see clinical utility in a conventional POC troponin device being used outside the ED—in primary care practice, for example, or ambulances? She is hesitant to endorse such testing. “As an ED physician I always get a little nervous when we do tests outside of an acute care setting. It makes people wonder why we’re doing the test and what we expect to get from the result. I’ve heard reasonable arguments from cardiologists that having a point-of-care device in their office would make a difference, in that they could assess myocardial injury,” she says. “But for the acute chest pain patient—I’d hate for them to have a test anywhere but the emergency department, especially if they’re coming in with acute chest pain.”

Studies have assessed conventional sensitivity POC troponin testing during ambulance transport. One such study evaluated a prehospital modified HEART pathway (PMHP) paired with in-ambulance quantitative conventional sensitivity POC troponin measurement, with the objective of improving prehospital triage (Stopyra JP, et al. PLoS One. 2020;15[10]:e0239460). Prospective application of the pathway and POC cardiac troponin during transport achieved high specificity and negative predictive value for 30-day major adverse cardiac events, offering “proof of concept that paramedics are able to accurately risk stratify patients with possible ACS, beyond STEMI recognition, by using a PMHP with POC cTn,” the authors write.

A clinical trial reported in 2015 randomized chest pain patients presenting by ambulance to usual care or conventional POC troponin testing in-ambulance (Ezekowitz JA, et al. J Am Heart Assoc. 2015; 4[12]:e002859). The patients who received POC troponin testing had a slightly shorter median time from first medical contact to discharge from the ED or admission to the hospital (8.8 versus 9.1 hours).

“So a decision and test-to-brain time frame for the treating physician went down,” Dr. Diercks says, though there’s “no real knowledge that that’s improved outcomes.”

“As we look at where patients can be best cared for in the U.S.,” she says, “whether they need to go to a percutaneous coronary intervention-capable setting, or a cardiac care center of excellence, having a point-of-care device may help ambulance drivers and emergency medical systems triage patients to appropriate locations, if it was known they had an elevated marker.”

Dr. Wu doesn’t dispute the need to get results faster and in pre-emergency department settings. “But from a clinical lab perspective, it kind of scares me,” he says. The POC device would have to withstand temperature, humidity, and mechanical stressors, and personnel would have to be trained. “In the emergency room I have absolute confidence that staff can deliver an excellent result time in and time out.” But elsewhere, “the training becomes a little more problematic.”

Quidel received a CE mark for the Triage­True High Sensitivity Troponin I Test and launched it in Europe in early 2019. Triage­True is the first POC assay on the market to meet the requirements for high-sensitivity troponin testing, Bill Ferenczy, senior vice president of the Quidel cardiometabolic business unit, said in an interview. Two criteria constitute a high-sensitivity assay, he notes: having a less than 10 percent CV at the 99th percentile of normal and the ability to measure troponin in 50 percent or more of a normal, healthy population. A completely different cartridge design was needed to make the Triage­True system work, he says, “but this allows users to perform the testing on the existing Triage MeterPro, a portable, 1.5-pound instrument that is already widely deployed worldwide.”

Quidel introduced the high-sensitivity POC test in Europe first with the intention, he says, of receiving FDA clearance and introducing the product in the U.S. after high-sensitivity troponin testing becomes better established in the U.S.

Another reason for the early launch in Europe was to enable studies that would validate the performance of the test against established central laboratory assays, Ferenczy says. A study conducted as part of the Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE), an ongoing prospective multicenter study aimed at advancing early diagnosis of MI, compared the test’s diagnostic accuracy with that of the hs-cTnT-Elecsys and hs-cTnI-Architect and found it to be at least comparable (Boeddinghaus J, et al. J Am Coll Cardiol. 2020;75[10]:1111–1124). And a low single cutoff concentration of less than 3 ng/L at presentation identified nearly one-half of patients as low risk with a negative predictive value of 100 percent (95 percent CI: 99.4 percent to 100 percent).

The study’s authors developed a zero-/one-hour algorithm specific to the POC hs-cTnI-Triage­True assay. That algorithm was found to have higher efficacy for direct triage toward rule-out or rule-in than the zero-/one-hour algorithms used with the central lab tests. Based on a single POC-hs-cTnI-Triage­True concentration at presentation, 43 percent of patients were directly ruled out or ruled in for MI without the need for serial hs-cTnI sampling, a higher proportion than for the hs-cTnT-Elecsys (25 percent) and the hs-cTnI-Architect (22 percent).

At this point, Ferenczy says, there are no data to show that the Triage­True improves medical outcomes or that it allows patients to be discharged more quickly. But now that the APACE study has demonstrated that the assay has diagnostic accuracy comparable to that of central lab analyzers, he says, “the second stage is to measure those impacts in hospitals that have implemented the test at the point of care.”

The clinical trial in the U.S. is underway, he says, adding, “It’s a significant one given the challenging requirements.” A launch in the U.S. would come in late 2022 or early 2023, Ferenczy says. “We fully expect other diagnostic companies, including Abbott and Siemens, to develop and pursue FDA clearance for high-sensitivity troponin on their point-of-care testing platforms and view this as validation of the market need for faster results.”

In the U.S., Quidel plans to target emergency departments in large hospitals, the laboratories of small hospitals, and the freestanding EDs and urgent care centers. “We’re going into places where we’re confident they can run the test the proper way,” Ferenczy says.

Large hospitals are leading the way with high-sensitivity troponin implementation, he notes, and testing at the bedside in their busy EDs can speed up diagnosis and patient disposition. The vast majority of hospitals in the U.S. are small and will be increasingly under pressure to move to high-sensitivity troponin, Ferenczy says.

“Many of them are already running contemporary troponin tests in the laboratory using Triage or similar point-of-care instruments. These approaches are simpler and more cost-effective in these low-volume settings. Triage­True will offer these small hospitals and similar low-volume settings such as freestanding EDs and urgent care centers a quick and easy transition to high-sensitivity troponin on a practical, cost-effective platform.” And they’re likely to do it in the lab, he says, “so they won’t have the complexity of training nonlaboratory personnel and everything else related to point-of-care implementation.”

Charna Albert is CAP TODAY associate contributing editor.