CardioExchange Archive

Last year, CardioExchange’s James de Lemos interviewed Dr. Martin Than about his ASPECT study, which looked at the use of biomarkers in the Emergency Department (ED) to successfully triage low-risk patients. We welcome Than back to discuss his new JACC study, ADAPT, which examines the use of TIMI score, ECG, and troponin I alone to determine if patients presenting to the ED with chest pain could be discharged in an accelerated 2-hour diagnostic protocol (ADP).

CardioExchange’s John Ryan interviews both Than and de Lemos about how patients with chest pain can best be managed in the ED and if this approach could decrease the observation period required for these patients.

Background:  In this observational study conducted at 2 urban EDs in Brisbane, Australia and Christchurch, New Zealand, blood was drawn on arrival and at 2 hours for troponin I testing using a contemporary central laboratory. Than et al found that, in patients with a TIMI score of 0 and no ECG changes, if troponin I was negative at 0 and 2 hours these patients could be safely discharged with early outpatient follow up (usually the next day). This protocol classified 20% (392 patients) of their ED population as low risk. Only one (0.25%) of these low-risk patients had a major adverse cardiac event (MACE), an NSTEMI, giving the ADP a negative predictive value of 99.7%.

Ryan: What is new with this study compared with last year’s study?

Than: There is not much difference. When we set up our cohorts in Brisbane and Christchurch we aimed to test both point of care (POC) and central laboratory testing processes. This study was run in parallel with ASPECT to answer a slightly different question. Although new POC assays are on the horizon, current commercially available contemporary central laboratory assays have better sensitivity compared with currently available POC assays. We wanted to address whether using multiple markers was necessary or if the current generation troponin I would work by itself. In reality, the diagnostic tools that we use in ADAPT are all available to us, and this made it very attractive to study.

de Lemos: Martin is too humble!  In my opinion ADAPT is a really important, and practical, extension of his prior work. ASPECT was groundbreaking because it explicitly incorporated risk assessment with a rapid biomarker rule-out strategy.  The limitation of that study, however, was that the biomarkers used were myoglobin (a marker that no one really knows how to use) and an insufficiently sensitive troponin assay. With this new study, they demonstrate that the principles of the prior study hold, and indeed are more powerful, using a simple rule-out strategy with troponin alone, incorporating troponin assays that are widely available in the U.S.

Ryan: How transferable are your findings to U.S. patients?

Than: I am always very cautious when asked this question, but I like to think that it would be safe. We have studied this in two countries, however, Australia and New Zealand are predominantly Caucasian without the large Afro-Caribbean population present in the U.S. Our next study will add to the evidence as we are examining the use of this algorithm in a randomized controlled trial, funded by the New Zealand-Health Research Council.

de Lemos: I think the findings are completely transferable.  Low risk is low risk, regardless of patient mix.  There may be a slightly lower proportion of U.S. patients identified as low risk by the algorithm (TIMI Risk Score of 0, negative ECG and troponins), particularly among African Americans, because baseline ECG abnormalities and chronically elevated troponins are more common among African Americans, due to a higher burden of hypertension, chronic kidney disease, and LVH.

Ryan: Can you put your work into context by comparing it with the recent NEJM article from Litt et al that looked at the potential use of CT angiography for safe discharge of patients with possible acute coronary syndromes (ACS)?

Than: They are reasonably complimentary. However, I do not think you want to CT angiogram everyone — there is obviously the (now small) radiation risk, the capital cost, and the challenges of the extra radiologists that you have to employ in order to have quick turnaround and reporting to make it useful. When you look at the CURE study, the group that was TIMI 0-1 had a 0.1% risk improvement (with clopidogrel) — these are the people that we are studying and that we triage with the ADP. So the NSTEMIs or UAPs that are missed would not benefit that much from NSTE-ACS therapies anyway. Then, in my mind, the intermediate group can go for a CT scan. The high-risk group should probably go straight to the cath lab, depending on your local area.

de Lemos: I think we dramatically over test the low-risk chest-pain population. Once they meet low-risk criteria as defined by the ADP algorithm or similar strategies, most of the necessary work is probably done.  I’m not convinced that most of these patients need additional testing.  Many of the abnormal test results have nothing to do with the presenting syndrome and represent incidental CAD in a patient presenting with non-cardiac chest pain.  I would hope that the quantitative work led by Martin and his group will lead not only to shorter observation periods and fewer admissions, but also eventually to less testing.  The risk is so low with a low-risk ADP that a watchful waiting strategy may be more appropriate than noninvasive testing.  Of course, someone has to have the guts to actually minimize follow up testing and then report the safety of such an approach!

Than: Dead right! One of the next challenges is to subdivide the ADP low-risk patients into those requiring and not requiring onward testing. If only we had a reliable biomarker of cardiac ischaemia or plaque formation!

Ryan: What about the physicians who claim that a good history is all you need to determine if someone is having an ACS?

Than: This comes up all the time: physicians say that they can take a history and determine who is at low, intermediate, and high risk. I would challenge you to find a paper that shows that history can be used in undifferentiated patients in the ED that have normal ECG and biomarkers to predict which of the rest of the patients will turn out to have ACS with sufficient sensitivity to safely discharge the patient home. Yes, one might get it right most of the time but there are plenty of patients with atypical histories that turn out to have an ACS. I can find paper after paper that shows that historical data are not as reliably predictive as we have been taught.

Generally, the historical variables that help are age, radiation, and relationship to exertion, but, even then, they do not hold up by themselves. Risk factors only seem to be useful in young patients (age is a stronger predictor and risk factors are not independent of age). The data just do not support the claim that physicians can accurately make the distinction with sufficient safety. Being right 99 times out of 100 would make someone a pretty good diagnostician, but if they saw several hundred patients with chest pain a year the numbers of missed cases would soon build up! In the setting of an undifferentiated patient, something more than history is required to make a definitive discharge decision — that is what we offer with this study and we have the evidence to support it.

de Lemos: When I was in training I thought a good doctor could talk to a patient and determine if their chest pain was cardiac…but all these years later I am no better than I was then.  I have a career’s worth of experience to tell me that there is no area in medicine that requires more humility than the chest-pain evaluation.  Physicians who say otherwise, and believe they can determine if ACS is present or not by history, are fooling themselves and putting their patients at risk.  This is why probabilistic algorithms, focused on risk and objective data, must guide the approach.

Ryan: Dr. Than, you say an interesting line in your paper: “In centers with lower disease prevalence, such as in the United States, it is likely that even more patients would be suitable for discharge to outpatient care with this ADP, which could potentially reduce extended observation in millions of patients annually.” Are you saying that in the EDs of the U.S., there is a lower disease prevalence? Why do you think that is?

Than: The prevalence of ACS in ED patients in the U.S. is much, much lower than in New Zealand, for example.  If you look at the MIDAS study, conducted at 18 academic EDs in the U.S., there is an ACS rate of 10%, whereas it is 30% in New Zealand. I believe this is because of very good access to primary care. General Practitioners (GPs) in Australia and New Zealand handle a lot of this care and it does not reach the ED. One impact of this is that in Christchurch, for example, the admission rate into the hospital from the ED is 50%. The GPs really do a great job of seeing lower-acuity patients. In that setting, if we can get 20% of people home even with our high incidence of ACS, then in the U.S. the numbers that can be discharged might end up being even higher with use of this ADP.

de Lemos: Martin’s absolutely correct about the low prevalence in the U.S. — and the differences may be even more extreme than he suggests.  In many chest-pain observation units in the U.S., the probability of ACS is less than 5%.  Whether this will translate into a higher proportion of patients found to have low-risk status by the ADP is a bit of a different question, however, because many of these patients have risk factors or prior CAD, and abnormal ECGs, so while they don’t have ACS, they still may not fulfill all the criteria for early disposition from Martin’s algorithm.  This sounds like a straightforward study waiting to be done.

Than: Fancy a collaboration, James?

Ryan: My uncle is in town this weekend — he is 55 years old with glucose intolerance. If he gets chest pain and has no ECG changes, am I asking the ED doctors to do a 2-hour rule out like in your study?

Than: It would be better if we did not individualize the results just yet. Institutions can look at these results and then decide as a facility or group whether they are going to change local policy over to the 2-hour ADP. So, no for this weekend, but maybe in a couple of months this option could be offered to your uncle after a good discussion between local cardiologists, internal medicine physicians, and ED clinicians.

de Lemos: I really think we’re ready to do this, provided the risk component is included, and provided the troponin assay is adequately sensitive. The only caveat would be if you brought him in very early after his chest pain started. I’d prefer in that circumstance that he hang around a few hours more.