and Alan Wu, PhD,
San Francisco General Hospital
Cardiac troponin (cTn) assays play an essential role in the diagnosis of acute myocardial infarction (AMI). Recently, the implementation of high sensitivity (hs) cTn assays has facilitated the use of triaging algorithms to enable the more rapid ‘rule-in’ and ‘rule-out’ management and stratification of patients with suspected MI using shortened protocols, such as the 0 hr/1 hr algorithm.
Of note, the accelerated rule-out protocols require rapid turnaround time (TAT) for prompt decision making and POC cTn testing may play an integral role in accelerating the management of patients with suspected MI. However, the clinical utility and need for a conventional POC cTn test is a matter of debate in the era of hs-cTn assays. In addition, there are no handheld hs-POC cTn testing devices available on the US market as yet. Here we present a Q&A with two thought leaders in both emergency medicine and laboratory medicine that will address several important questions regarding the technical, clinical, and practical aspects of POC cTn assays.
Q: What is the proposed evidence of benefit to the emergency department of POC cTn?
Deborah Diercks: This comes down to a key factor that we look for as emergency physicians: can we do things in a more time efficient manner? The argument to justify the use of POC cTn is common—a rapid result leads to faster determination of disposition (patient is either admitted or released), earlier initiation of treatment, and decreased patient length of stay (LOS) in the ED. As expected, one challenge to taking this concept into implementation is that we do not have broad and robust data to indicate a reduced LOS, for example.
It is clear that POC cTn provides a faster result, but what is less clear is whether POC cTn results would drive disposition and admission decisions given the numerous additional aspects of chest pain patient workup, such as x-ray need or other considerations in the differential. Each of these evaluation components takes time and vary based on the patient. So, although POC cTn may provide a rapid result, if that rapid result does not change the patient’s disposition trajectory or LOS, it may not add as much value as we might hope. That said, there are many who believe POC applications do enable a faster determination of disposition. Yet, trepidation remains in the high sensitivity cTn era given the ability to detect such significant myocardial injury that we cannot easily differentiate patients whose injury is from MI without more information resulting from the patient evaluation.
Alan Wu: On another note, it would be helpful to distinguish between the POC devices that are not high sensitivity from the ones soon to emerge on the market that seek to fulfill the high sensitivity requirement. It is my opinion right now that we are not truly ready. Without high sensitivity, we are not benefiting from an early rule-out of accelerated protocols.
Consider the following scenario: You employ a zero-, one-, and three-hour rule-out protocol for MI. The one-hour sample does not produce a positive result using the conventional sensitive POC assay, but after sending the sample to the central lab for testing with a high sensitivity assay, you are able to rule out. In this case, you have gained the two additional hours, because in the case of POC testing only, you would have to wait three total hours to rule out. In contrast, even though processing the sample through the central lab takes 45 minutes to results, AMI rule out may still may be faster. Until we have both the availability of FDA-cleared, POC hs-cTn, and robust documentation of its efficacy, I remain skeptical.
Q: What are the ideal features of a POC hs-cTn device?
Wu: A true POC device should be handheld and easily transported from patient to patient. A different instrument, such as a benchtop reader, that must be placed in a central location (even within the ED) should be viewed as “near patient,” as opposed to POC. These near patient devices can, for example, process whole blood and produce good results, but the sample must be physically transported to the place where the testing is done, as opposed to bringing the device to the patient. The decision to implement either of these two platforms depends, in part, on the layout of the ED. Some EDs employ a decentralized structure involving a small ED lab into which different ED beds can feed. In some of these cases, if the ED is large enough that you must walk a long distance to bring a sample to the ED lab, perhaps it makes more sense to send the sample into the central lab anyway.
Diercks: When considering POC testing from the ED physicians’ point of view, we think about immediate bedside. A POC test that I have to send somewhere or take somewhere likely does not provide the time savings that a true bedside test provides. Transporting samples, even a relatively short distance, can add additional patient care burden onto nurses and other clinicians in what may be a very busy ED with a large volume. To change these practices somewhat dramatically, we would need a true POC test at the bedside.
Q: What are the appropriate settings for using POC cTn?
Diercks: As an ED physician, I am inherently anxious about testing outside of an acute care setting. I have heard reasonable arguments from cardiologists and other clinicians that having a POC device in their offices would make a difference in assessing whether a patient is suffering myocardial injury. But, for patients experiencing acute chest pain, I prefer testing be done in an ED environment.
That said, as we create regionalized centers of excellence in health care and study where patients can be best cared for, having a cardiac POC device may help ambulance and emergency medical service (EMS) personnel triage patients to appropriate locations in the event of a known elevated cardiac marker, whether that be a percutaneous coronary intervention (PCI) capable setting, cardiac center, or other emergency location.
Furthermore, cardiologists’ offices are another reasonable, pre-hospital location where a POCT device could help evaluate acute chest pain. We need to take the opportunity to review the placement of our resources and how best to direct patients. An additional important consideration involves integration with the electronic medical record (EMR). The inability to do so could be problematic if POC test results cannot be easily interfaced with the EMR during patient evaluation.
Wu: It is difficult to dispute the medical need for rapid results in the pre-ED settings just mentioned, but from a clinical laboratory perspective, such a device needs to be incredibly robust; be able to withstand fluctuating temperatures, humilities, and mechanical stresses. Training of various personnel also must be acknowledged, as skill sets vary across practice areas.
Otherwise, I have absolute confidence that ED staff can deliver excellent result times. Keep in mind that proficiency testing is needed, as well as regular staff competencies on the proposed device(s) and other QC and QA procedures. Outside these areas, when considering distributing such a POCT device to general physicians’ offices, patient homes, cruise ships, etc, training becomes more problematic, as would documentation of proficiency, maintaining adequate supplies, adherence to reagent expiration dates, and so on. As laboratorians, maintaining strict control over these variables is ingrained, so these non-lab locations are less than ideal. Again, rapid access to accurate information is always desirable, but many factors must be accounted for when proliferating a POCT device and methodology.
Q: How are POC hs-cTn tests viewed from a cost-effectiveness standpoint?
Wu: I can respond from an instrument and reagent standpoint, but Dr. Diercks can respond in terms of ED workflow, where I think there can be very real cost savings. In terms of the physical devices, I assume they will be inexpensive, but cost increases are likely for the necessary cartridges. These will be more expensive than the liquid reagents we use in our central laboratory analyzers. Likewise, these large central analyzers are indispensable, whereas a POCT would be supplementary. Therefore, the costs for acquisition and maintenance of lab analyzers should not be included in cost estimates. From the laboratory view, the primary cost drivers will be those of the consumables, calibrations, and labor, and these costs are likely to be higher for a POCT at this point.
Diercks: Dr. Wu mentioned the exact kinds of key components and alluded to where we could find cost saving with POC, and that is in revolving ED beds and allowing us to see more patients. Right now, in the type of chronic setting I work in, we use hs-cTn, but we would only run the test once if it is below the limit of detection. If that patient is low risk per a risk-stratification score such as the HEART score, we can stop testing that patient. Keep in mind this is only about 25% to 30% of the patients we see in the ED; everyone else will get serial tests.
In the era of serial tests, the cost savings on throughput are not substantial. When you balance the magnitude of the decrease in patient LOS in the ED with the analytical issues mentioned by Dr. Wu, I am squarely in the middle of the question. Perhaps it will be cost effective, but we do not have enough information at this time to make a definitive judgement.
Q: Is there a case for both POC and lab-based troponin to be used in the ED?
Diercks: Before we adopted hs-cTn, we performed both conventional POC tests and lab-based troponin tests. When we implemented the hs-cTn, we—ie, a consensus of the pathology, cardiology, and emergency medicine departments—decided to forgo the conventional POC test. We felt we would get greater value, and more information, per test by standardizing the assay and platform, which is hs-cTn. It was a substantial decision to make that change because doing so necessitated a well-defined algorithm to determine how to implement new hs-cTn testing.
Wu: This question brings us back to the sensitivity of the test. If the POC device features an assay with conventional sensitivity, the speed to result is less important, especially if a second specimen or a central lab test is required. However, if we are talking about a hs-cTn assay, even lacking standardization with the central laboratory, you will be able to rule out 60% of patients within the first one to three hours and not need a central lab result. We can then better manage the other 30% to 40% who have legitimate risk and may need an updated baseline. Eliminating over half of the potential risk pool early on would obviously be quite advantageous.
Q: What department would best drive the adoption of hs-cTn in a hospital setting?
Diercks: This has been an interesting journey for us. Clearly, the lab has a significant role in determining the type of assay and vendor to choose. And ultimately, joint engagement between the lab, cardiology, and the ED to define and create the implementation pathway is key. Both cardiology and ED representatives should work with the lab to address several details, including defining initial critical/alert thresholds for hs cTn and how to effectively interface with the information system such that it drives clinical decision making. In our case, the initial response was driven by the laboratory to choose the platform, and then the ED and cardiology working with the lab to optimize implementation.
Wu: I certainly agree with that approach. I think it can be initiated by the lab, but it should be driven by the medical practices. This starts by assigning a champion who is knowledgeable of the differences between conventional and hs cTn and is representative of cardiology and/or ED medicine. As the ones responsible for triaging and outcomes of these patients, they should have governing approval of the adoption. Regardless, it will benefit many smaller hospitals once larger facilities can produce a wider range of data and information to define the scope of adoption.
Q: Is there a preference between hs-cTnT versus hs-cTnI?
Wu: From the laboratory perspective, it is unlikely for a hospital to acquire a troponin T assay if they do not have the instrumentation already in place. It would be challenging to justify acquiring a new instrument based on whether a clinical practice is used to T or used to I. In this case, some drivers are completely economic and based largely on common sense.
Diercks: This is indeed a laboratory-based financial decision and will be largely based on a specific hospital’s instruments and whether there is assay standardization. I will say, in my experience, hs-cTnT and hs-cTnI are not the same and they produce different results. So, whichever one the hospital decides to use, it is important for all relevant clinicians to be aware of the implications and understand the differences between the assays. It is likewise important to acknowledge that this is not a one-size-fits-all solution, and largely depends on the assay and the type of troponin being employed at the facility.
Deborah B. Diercks, MD, MSc, is professor and chair of the department of emergency medicine at The University of Texas Southwestern Medical Center in Dallas, Texas. Deborah oversees the emergency medicine programs at Parkland Memorial Hospital and UT Southwestern University Hospitals, which together constitute one of the largest emergency medicine programs in the nation. After receiving her undergraduate degree in microbiology and immunology from the University of California, Berkeley, she earned her MD at Tufts University School of Medicine. Deborah completed her residency in emergency medicine at the University of Cincinnati. She also holds a master’s degree from the Harvard University School of Public Health.
Alan H.B. Wu, PhD, DABCC, is chief of clinical chemistry and toxicology at San Francisco General Hospital, as well as professor of laboratory medicine at the University of California, San Francisco (UCSF), where he serves as medical director of the clinical pharmacogenomics laboratory. He earned his doctorate in analytical chemistry from the University of Illinois, Champaign-Urbana, and performed post-doctoral fellowships in clinical chemistry and a toxicological chemistry at Hartford Hospital in Connecticut. Alan is certified by the American Board of Clinical Chemistry in clinical chemistry and toxicological chemistry, and his research interests include pharmacogenomics, clinical toxicology, cardiac biomarkers, and point-of-care testing. With over 400 publications in peer-reviewed journals, he has also written six books designed to promote the value of the clinical laboratory to the general public.