May 29th, 2012

Two-Hour ADP Can Safely and Rapidly Discharge Low-Risk Patients

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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.

6 Responses to “Two-Hour ADP Can Safely and Rapidly Discharge Low-Risk Patients”

  1. David Powell , MD, FACC says:

    Time from chest pain onset is an important factor. Information on this would be helpful. Also, an increase in troponin from the first to the second assessments..without meeting the 99% threshold (say by 0.03)…would be a concern.

  2. Dear David
    Thanks for making these comments. Although we have looked at time from symptom onset I do not have this data easily at hand and providing it and could take some time depending on where my request goes in the data analysis queue. Some data specific to a Christchurch sub-cohort are available in the publications referenced at the bottom and overall the statistics were in Christchurch:
    Median time from symptom onset = 6.6 [IQR = 4.1 to 13.2] hours

    The ADP is designed to work independently of this (irrespective of time since symptom onset) because we have found that patient reporting of this is can be very inconsistant and two hours is not long to wait for a diagnostic protocol to run its course. In ADAPT there were early presenters (<3 hours) with MACE and they were detected.
    The false negative case presented 3.5 hours after symptom onset.

    Thanks for raising the point about dynamic change (delta). I think that you are correct that someone presenting with symptoms and a change from <0.01 to 0.02 over two hours would have me worried and the false negative case went to 0.03 at two hours (actually 0.027). Since the parameters of the ADP as an index test were set 'a priori' we have reported the ADAPT study as it is. I cannot tell you off hand what the trade off would be in terms of decreased numbers patients classified as 'low-risk' if some sort of 'delta' criteria was added for patients with both results <99th percentile. One comment that I would make about that is that the current crop of TnI assays are not really suited to making reliable assessment of dynamic change because their analytical reproducability (coefficient of variance) at these low levels is not reliable enough. This will be a positive aspect of high sensitivity assays.

    Thanks again for your comments
    Best wishes
    Martin Than

    Diagnostic and prognostic utility of early measurement with high-sensitivity troponin T assay in patients presenting with chest pain.
    Sally J Aldous, Mark Richards, Louise Cullen, Richard Troughton, Martin Than
    Canadian Medical Association Journal . 01/2012; DOI: 10.1503/cmaj.110773

    A New Improved Accelerated Diagnostic Protocol Safely Identifies Low-risk Patients With Chest Pain in the Emergency Department.
    Sally J Aldous, Mark A Richards, Louise Cullen, Richard Troughton, Martin Than
    Academic Emergency Medicine . 05/2012; 19(5):510-6. DOI: 10.1111/j.1553-2712.2012.01352.x

  3. Carlos A Selmonosky, MD, MD says:

    This is a very good work that will help to reduce cost for patients admited to the ED because of chest pain;it will also reduce the already very small number of patients whom are discharged with an undiagnosed ACS.But paraphrasing Chesterton “It is that they can’t see the solution.It is that they can’t see the problem”.
    I am refering to the many thousand of patients discharged from the ED with a diagnosis of NCCP,they are condemned to a multitude of overdiagnosis with very expensive non diagnostic tests. Because Thoracic Outlet Syndrome has not been considered and the relative weakness of the fifth finger has not been tested in the physical examination.See

    • Dear Carlos
      I know what you mean about NCCP. I think that local circumstances have a big impact on the extent of this. My wife, is a local GP (family physician), tells me that it is unusual for her to see patients with ongoing chest pain issues after then ACS screening process in hospital but I am sure that may not be true elsewhere and I know that there are plenty of these patients in cardiology outpatients. Certainly, my personal experience is that the medical profession (after the collective sigh of relief that pain is not cardiac) does not do a very efficient job of how to investigate those with on going pain. There is more work to do in that area and part of the problem may be that this crosses the boundaries between primary and secondary care.
      Thanks for the web-link it is very interesting
      Best wishes

  4. Jean-Pierre Usdin, MD says:

    Good on you!
    I totally agree with the conclusions of this study as I did one year ago with ASPECT (which included also Asian people if I remember well)from the same investigators.
    this study wrings definitely ROMICAT II and ACRIN PA’s studies neck!

    no need for Coronary artery computerized tomography in patients at low risk of ACS! they can be discharged safely and radiations-free, with this three points testing.
    so please leave the radiologist on call at home with his sometimes evasive judgments “May be there is a 50% stenosis on this right artery” or “no way this is a reconstruction artifact!”
    now we have to convince our ED colleagues of the useless interest of CACT in ACS low risk patients.

  5. Dear Jean-Pierre
    Thanks for your comments

    I think that you have highlighted an important next step in the research process.
    As mentioned in the main interview – “One of the next challenges is to subdivide the ADP low-risk patients into those requiring and not requiring onward testing”.
    We have definitely encountered cases in practice amongst the low-risk ADP pathway where critical stenosis(es) requiring intervention was discovered following positive follow-up investigations, (with one patient having a STEMI before angiography and PCI occurred). Our current approach is to do some form of onward testing on everyone discharged through this ‘fast-track’ protocol though the most common test used by us is exercise stress test (for all its flaws).

    Working together with your ED colleagues (and laboratory community) to review and refine local strategies for the investigation of possible ACS sounds like a good approach to address local issues about CTCA use. Speaking from experience, I can say that in the past we used to have quite a few tensions between specialities on similar issues. After a concerted effort to collaborate together towards common patient centered goals (focused around doing some research together, which was a good icebreaker), we now have a better appreciation of each others points of view and clinical focus.
    e.g. (i) the laboratory – analytical issues, (ii) cardiologists – ‘rule-in’ and (iii) ED – ‘rule-out’.
    We now have a good working relationship btween the speciality groups

    This is an interesting topic area – as it happens I will be in Paris in July, so maybe we should take the opportunity to touch base over it – know any good restaurants?!!
    Anyway, do stay in touch, you can contact me via
    I enjoy the dialogue, it is healthy and often leads to new ideas
    Best wishes
    Martin Than