Whether you are aware of it our not, three major assumptions are present when employing any diagnostic strategy in the Emergency Department. First, that the diagnostic test in question will identify a group of patients at risk of a poor outcome due to an otherwise undiagnosed process. Second, there is an effective therapeutic intervention that will avert said outcome. And third, by discovering this process early, the intervention in question will be more effective than if we wait for the disease to manifest clinically obvious characteristics. These assumptions are frequently based purely on physiological reasoning and good intentions. In the history of medicine, good intentions and physiological reasoning are poor surrogates for patient oriented outcomes and often fail to survive the test of scientific inquiry
Such is the case of non-invasive cardiac testing. Despite multiple studies suggesting its ineffectiveness, the stress test has maintained its lofty position for the management of patients presenting to the Emergency Department with chest pain.
A recent study published in JAMA Internal Medicine (1), Sandhu et al utilized a large insurance claims database to identify patients that presented to the Emergency Department with chest pain and compared outcomes in patients who did or did not undergo non-invasive testing. The authors used a fairly novel and elegant approach to control for the many imbalances one would expect from such a large, heterogeneous, non-randomized cohort. Using what is called an instrumental-variables approach, the authors exploited the fact that care is not delivered consistently across all 7 days of the week. Their premise, according to previous data, is that patients seen in the ED during the weekend (Friday-Sunday) were less likely to undergo stress testing than those that presenting during the week (Monday-Thursday), based not on differences in patient level characteristics, but rather the universal distaste of working on the weekend.
After excluding patients with diagnoses suggestive of acute ischemia (AMI, intermediate coronary syndrome, acute coronary syndrome without coronary occlusion, and other acute ischemic heart disease), as well as patients with an alternate diagnosis that could explain the chest pain, the authors identified 926,633 unique adult ED visits from 2011 to 2012. Unsurprisingly patients who received testing were older, with more risk factors than patients who did not undergoing testing. Conversely, patients who presented for evaluation on the weekend appeared to be fairly similar at baseline when compared to those that presented during the week.
As the authors predicted, patients evaluated on the weekend underwent less stress testing (defined as patients who underwent testing within 2-days of presentation), when compared to those that presented during the week (18.18% vs 12.30%). They also observed more early angiography (2.10% vs 1.30%) and downstream testing, defined as any invasive or noninvasive testing done over the next 30-days (26.10% vs 21.35%). Even after adjusting for possible bias, not controlled for with their instrumental approach, the authors noted an increase in the rates of invasive angiography in patients who presented on the weekday when compared to those who presented on the weekend. They also note that this increase in invasive or non-invasive testing did not lead to an observed decrease in the rate myocardial infarction. Suggesting stress tests do not decrease the number of MIs in patients presenting to the Emergency Department with symptoms concerning for ACS.
Despite the elegance with which these authors manipulated this large unwieldy dataset, its innate structure creates the potential for multiple sources of bias that cannot be controlled by any statistical manipulations. That being said, their results are fairly consistent with the majority of the previous literature examining non-invasive stress testing. More importantly, the stress test has failed to meet the three initial assumptions required when examining any diagnostic testing strategy.
The concept that non-invasive stress tests identify a population that are at higher risk for a myocardial infarction is based on fairly poor data. Amsterdam et al published the results of their prospective dataset claiming that the patients with positive stress tests were at significantly higher risk of adverse events than those with a negative test (17% vs 0.16%) (2). The reality is somewhat different. These authors enrolled 1000 patients presenting to the Emergency Department with chest pain who had both a negative EKG and initial troponin, and performed exercise stress tests. Of the cohort 640 had a negative stress test and were discharged directly home. Only one had a MI during the follow up period. Of the 125 patients with a positive stress test the vast majority of the adverse events were revascularization procedures (12) and only 4 were MI. In fact, on closer examination all 4 MIs were identified on the second troponin in the Emergency Department. And so in reality this study demonstrates that patients presenting to the ED with a negative EKG and two negative troponins are already at fairly low risk for a myocardial infarction over the next 30 days. In fact, the only thing the stress test added was to increase downstream invasive procedures. This is not the only trial to demonstrate that stress tests add nothing to the diagnostic yield of EKG and cardiac biomarkers (3). And these results are not limited to exercise stress tests. Even more anatomically accurate forms of tests, such as CTCA have failed to demonstrate a decrease in the rates of death or MI when used in an Emergency Department population (4). This in part is likely due to the fact that we have stratified these patients to such a low risk using EKG and cardiac biomarkers, that any further risk stratification is likely to result in more harm than good (5,6).
But let us say for the sake of argument stress tests do in fact identify a subset of patients who are at higher risk for myocardial events, to what end? There is no discernible evidence demonstrating the cohort of patients identified by positive non-invasive testing will benefit from invasive catheterization. In fact, the majority of the data in patients not actively experiencing a myocardial infarction would favor medical management alone (7,8). And so, without an effective means of preventing the prophesized myocardial consequences, stress testing is only capable of causing unneeded downstream testing, interventions, and harms.
I am sure our hesitancy to discard this needless diagnostic strategy is in part because no one has suggested a viable replacement. And while the right answer may in fact be simply to do nothing, such self-restraint is rarely palatable to the modern physician. But a bad solution is not better than no solution, especially when it has the potential to hurt patients. Surely given the ever growing literature base discrediting non-invasive stress testing on Emergency Department patients, I think the real question to ask is, just who exactly are we treating when ordering these potentially harmful and costly tests, us or the patient?
Sources Cited:
- Sandhu AT, Heidenreich PA, Bhattacharya J, Bundorf MK. Cardiovascular Testing and Clinical Outcomes in Emergency Department Patients With Chest Pain.JAMA Intern Med. Published online June 26, 2017. doi:10.1001/jamainternmed.2017.2432
- Amsterdam EA, Kirk JD, Diercks DB, Lewis WR, Turnipseed SD. Immediate exercise testing to evaluate low-risk patients presenting to the emergency department with chest pain. J Am Coll Cardiol. 2002;40(2):251-6.
- Gibler WB, Runyon JP, Levy RC, et al. A rapid diagnostic and treatment center for patients with chest pain in the emergency department. Ann Emerg Med. 1995;25:1–8
- Hulten E, Pickett C, Bittencourt MS, et al. Outcomes after coronary computed tomography angiography in the emergency department: a systematic review and meta-analysis of randomized, controlled trials. J Am Coll Cardiol. 2013;61:(8)880-92.
- Hermann LK, Newman DH, Pleasant WA, et al. Yield of routine provocative cardiac testing among patients in an emergency department-based chest pain unit. JAMA Intern Med. 2013;173(12):1128-33.
- Foy AJ, Liu G, Davidson WR, Sciamanna C, Leslie DL. Comparative effectiveness of diagnostic testing strategies in emergency department patients with chest pain: an analysis of downstream testing, interventions, and outcomes. JAMA Intern Med. 2015;175(3):428-36.
- Stergiopoulos K, Brown DL. Initial coronary stent implantation with medical therapy vs medical therapy alone for stable coronary artery disease: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(4):312-319.
- Stergiopoulos K, Boden WE, Hartigan P, et al. Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials. JAMA Intern Med. 2014;174(2):232-40.
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Great post. I agree wholeheartedly, both with respect to the specific paper and the general issue with providing low value care for the sake of doing something. We need to start addressing this earlier in medical education. Physiology lectures ought to have a disclaimer “this is all a fairy tale.”
Or the title of the lecture should be:
Human Physiology and other delightful fairytales
Thanks Jordan, as always greatly appreciate your input!
I’m not sure how this would prove physiology to be useless? I’d rather say that we know physiology to be complicated. That atherosclerosis is a systemic disease, poorly treated by stenting discrete lesions unless these are actively causing MI (unless your goal is to reduce the burden of angina in a severely symptomatic person, rather than to prevent MI or death). I’d argue that we know that stress tests don’t even reliably prove or disprove myocardial oxygen supply limitation, given how electrically alone the healthy exercising heat and the heart with limited ischemia can be. I’d venture that many patients… Read more »
Great comments Maarten. I think you have found an alternative physiological explanation to explain why stress tests do not identify the patients at risk for unidentified ACS after an ED workup. But the point is the physiologically underpinning of why we did stress tests in the first place doesn’t seem to be supported by the empiric evidence. Like I said in my closing paragraph I think a lot of the hesitancy to stop this unhelpful, potentially harmful practice is because we don’t have a “better” option. I tend to think that for the majority of patients we evaluate in the… Read more »
Why do you say physiological reasoning is a poor surrogate and fairytale?
Not talking about this topic in particular but…
Sometimes i think that evidence based medicine lacks some physiology and common sense.
We see so many pitfalls and tricks to alter the papers results…and we take care of patients one day in one form, and the next year sometimes the opposite way…
I found hard to explain this feeling i have….hope you can understand.
PS: sorry for my english!
Great post – like many of us I often feel conflicted about referring a patient who has ruled out for MI for stress testing for the reasons you mention. However, is there really NO way for non-invasive testing to EVER help a patient? Let me explain what I mean. I fully agree that there is no evidence that stable angina derives any mortality benefit from revascularization, However, if a patient with previously undiagnosed coronary artery disease fails a stress test, this does provide a trigger for optimizing medical therapy in the form of aspirin, statin, BP management, smoking Cessation, etc.… Read more »
Thanks Chris, I see what you are saying but I think the literature doesn’t bear this out either. The best example of this was the the SCOT-HEART trial (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60291-4/abstract) I’ve written about it in detail here: In brief, all patients received a full standardized evaluation after which the treating physician assessed the patients baseline risk of CAD and determined what further testing and treatment strategies he or she would recommend. After the patients were randomized to either receive CTCA or standard care. At 6 weeks the physicians were then asked again to assess the likelihood of CAD(11). What the authors… Read more »
Thanks for your reply! You make a very good case!
Thanks for another great post Rory. Reminds me of the Atlantic article from a couple of months back. Great stuff.
https://www.theatlantic.com/health/archive/2017/02/when-evidence-says-no-but-doctors-say-yes/517368/
Great work analysis and explanations as always Rory. As an Aussie it seems like we could do a similar trial comparing outcomes of cohorts across the Pacific- we do a lot less stress testing acutely As a GP – we see these folks weeks, months later…. and they probably get greatest benefit from the “wake up call” of going through the ED wringer and contemplating changes to lifestyle The EST is often the only exercise the patient has attempted for years and can be inspirational to “get back in shape” Hate EST as a test- love it as a motivational… Read more »