Andrew D. McRae (@Andrew_McRae_EM) and James E. Andruchow

“Most ED chest pain patients with non-ischemic ECGs and low-risk high-sensitivity troponin results do not require additional objective cardiac testing.”

Chest pain is one of the most common reasons for visiting EDs across the developed world. Most patients have non-ischemic electrocardiogram (ECG) findings and normal cardiac troponin concentrations and, in Canadian EDs, are subsequently discharged home without additional investigations. The risk of short-term major adverse cardiac events (MACE) among patients with low-risk ECG and normal conventional troponin concentrations has been quoted as 2%–5%,^{Reference Christenson, Innes and McKnight1} with the risk of missed myocardial infarction (MI) being only 0.2%.^{Reference Morgenstern2} Validated high-sensitivity troponin diagnostic algorithms have an even lower risk of missed acute coronary syndrome (ACS) than earlier-generation troponin assays.^{Reference Stopyra, Riley and Hiestand3} In spite of the exceedingly low risk of adverse events in these patients, and even after clinical risk stratification with a tool such as the HEART score, 40%–70% of patients with chest pain may undergo additional objective testing such as exercise stress testing, myocardial perfusion imaging, or coronary CT angiography (CCTA) after an MI has been ruled out.^{Reference Stopyra, Riley and Hiestand3} This leads to substantial unnecessary resource utilization, false-positive additional testing, and iatrogenic harms for low-risk patients.

Proponents of early objective testing (particularly CCTA) recommend objective testing for nearly all patients who have had MI ruled out in the ED. Arguments in favor of objective testing often quote the very high negative predictive value (NPV) of CCTA for MACE and clinically significant coronary disease, and compliance with American Heart Association recommendations to screen for coronary disease after ruling out MI.^{Reference Hollander, Than and Mueller4}

We disagree with this advice for several reasons. Firstly, guidelines recommending objective testing of low-risk patients were developed long before the availability of high-sensitivity cardiac troponin (hs-cTn) and do not reflect the improved diagnostic performance of these assays. Patients who have had MI ruled out with hs-cTn have a substantially lower risk of MACE than those patients evaluated using conventional troponin assays, and therefore early objective testing for patients should have a much more limited role in the high-sensitivity troponin era. Secondly, there is ample evidence that a liberal testing strategy does more harm than good. Positive stress test findings in low-risk patients are most frequently false-positives, and recent evidence suggests that CCTA use in low-risk patients increases rates of angiography and revascularization (and their attendant complications) without improving patient-centred outcomes such as downstream MI risk.^{Reference Foy, Liu and Davidson5} Thirdly, the high NPV of an objective testing strategy is largely a function of the inherent low-risk of the population being tested, rather than the performance of the test itself. Finally, the available objective testing modalities, including exercise stress testing, myocardial perfusion imaging, and CCTA, have worse predictive performance for MACE risk than hs-cTn testing. Using a diagnostic test with worse test characteristics to further evaluate patients with low-risk hs-cTn findings simply makes no sense.

Surveys of Canadian emergency physicians suggest that the acceptable risk of missed ACS is 1%–2%.^{Reference MacGougan, Christenson, Innes and Raboud6} For patients with an ACS risk of less than 2%, the harms associated with objective testing likely outweigh the benefits.^{Reference Kline, Johnson and Pollack7} We believe that patients with a 2% or lower risk of 30-day MACE are unlikely to benefit from additional testing. ED chest pain patients who have low-risk ECG and hs-cTn results generally have a short-term MACE risk below that threshold.

A large meta-analysis of recent literature has shown that the combination of a non-ischemic ECG and an undetectable hs-cTn concentration at ED arrival is over 98% sensitive for 30-day MACE.^{Reference Pickering, Than and Cullen8} Put another way, of all patents with MACE, less than 2% of patients with be missed using a single undetectable troponin strategy. These patients (approximately one-third of all ED chest pain patients) simply do not need additional objective testing. Similarly, a 1-hour serial testing algorithm with high-sensitivity troponin has a sensitivity for 30-day MACE of over 98% and was applicable to 43% of patients.^{Reference Mokhtari, Lindahl and Schiopu9} Based on these estimates, it appears to be both feasible and safe to use an ECG and biomarker-only strategy to identify patients who need not be referred for additional cardiac testing after an ED evaluation for chest pain.

Frank Scheuermeyer and Jim Christenson

“A negative troponin does not rule out serious coronary disease.”

Acute chest pain is responsible for over 8 million visits to American EDs annually. Historically, 2%–5% of patients with chest pain who had an ACS within 30 days were discharged from the ED with an incorrect minimizing diagnosis and no follow-up,^{Reference Christenson, Innes and McKnight1} and emergency physician tolerance for “missed MI” has been estimated at 2%.^{Reference MacGougan, Christenson, Innes and Raboud6} To reduce the chance of such missed events, the American Heart Association/American College of Cardiology guidelines have long endorsed prolonged observation, serial cardiac investigations, likely admission, and probable follow-up investigations such as echocardiography, exercise stress testing, nuclear medicine scanning, or CCTA.^{Reference Amsterdam, Wenger and Brindle11} These tests are often performed in a population with a low pretest probability of disease, and false positives may outweigh true positives.

However, the aforementioned studies were conducted 2 decades ago and new techniques have ensured that the “miss” rate of MI (acute) is now less than 1%;^{Reference Hollander12} moreover, it seems likely that acute myocardial infarction (AMI) can be ruled in^{Reference Mueller, Giannitsis and Christ13} or ruled out^{Reference Pickering, Than and Cullen8,Reference Mokhtari, Lindahl and Schiopu9} with a single high-sensitivity troponin test (hs-cTn). Given that, in North American settings, less than 10% of ED chest pain patients are diagnosed with ACS within 30 days, and that EDs are increasingly crowded, it may be tempting to accept a 1% “miss” rate and quickly discharge chest pain patients who have a non-ischemic initial ECG and a negative hs-cTn.

Additionally, while a single ECG and negative hs-cTn may rule out AMI, some patients may benefit from additional observation – for example, to capture additional pain episodes – or sequential ECGs or biomarkers. Patients with more subtle ACS presentations, such as unstable angina, may often only be diagnosed with a careful history and physical examination, or minor yet dynamic ECG changes, and these elements in will be lost in some patients if the chest pain evaluation is condensed to a seemingly normal ECG and single negative hs-cTn.

While these chest pain patients do not appear to have an MI or die within 30 days, it is challenging to endorse that all patients without abnormalities during a single episode of objective testing can be discharged directly to primary care follow-up of variable timing and quality. Unfortunately, the goal of scoring systems such as HEART^{Reference Backus, Six and Kelder14} is to provide an estimate of the risk of ACS or MACE, and, although this estimate may be accurate on a population level, when personalized care is considered, there are likely many patients who are at zero risk and some who are at elevated risk. For example, both a 35-year-old smoker and a 64-year-old with severe chronic kidney disease could have similarly low HEART scores, yet one would expect the latter to have a far higher MACE risk. Although such scores are popular, they do not necessarily provide emergency physicians with evidence-based advice for post-discharge care for the individual patient.

Indiscriminate discharge of chest pain patients with apparently low-risk stories and negative investigations may not be wholly safe. In 1,116 consecutive chest pain patients at a single Canadian site, 17% of patients were admitted, whereas 23% were discharged with outpatient provocative cardiac testing. Of the 120 patients (10.8%) with ACS, one-fifth was diagnosed only when they had a high-risk outpatient test.^{Reference Scheuermeyer, Innes and Grafstein15} While it is important to realize that this protocol did not employ hs-cTn, it is apparent that patients may derive benefit from additional testing; unfortunately, there is currently no widely accepted cohort of patients who may safely forego testing.

Two prospective analyses may furnish physicians with further evidence. The no objective testing rule, which have been developed in 2,396 Australian and New Zealand chest pain patients with a 5.3% ACS rate, demonstrated that 31% of patients could safely be discharged home with no further testing, although this requires validation.^{Reference Greenslade, Parsonage and Than16} The Vancouver chest pain rule enrolled 1,669 patients at a single urban site with a combined 17.0% 30-day ACS rate, and developed and validated an algorithm that enabled safe early discharge of 21% of patients without additional cardiac-specific testing.^{Reference Scheuermeyer, Wong and Yu17} While there is a positive association between positive testing, coronary artery disease, and ACS/MACE, patients who did not have a 30-day ACS outcome may still have benefitted from testing. Conversely, those who had a 30-day ACS outcome may not have benefitted from further testing if treatments were not altered or offered. However, in the absence of any other evidence, these studies assist physicians by confirming that within a heterogeneous pool of chest pain patients, they can be reasonably confident that selective outpatient testing is acceptable.

In addition, there is a cohort of patients with potential ACS who do not present with classic chest pain symptoms (they may complain of nausea, weakness, shortness of breath, or back or abdominal pain), and such patients have been little investigated by studies that generally limit entry criteria to acute chest pain. As such, even though emergency physicians may manage these patients as “rule out ACS” or chest pain equivalents, there is little evidence on which to base this practice. In particular, female patients, the elderly, and diabetic patients may present with alternative complaints, and may therefore be systematically underrepresented in current research. In these patients, although additional provocative testing may not necessarily diagnose an ACS, discharge after a single troponin may not be warranted.

Finally, most research has focused on the outcomes of ACS and MACE. However, this may not even cover all relevant cardiovascular outcomes. Even the most rigorous studies have not ascertained the potentially important 30-day outcome of new acute heart failure,^{Reference Shah, Anand and Strachan18} which most patients and physicians would likely consider relevant. It is important to note that physicians developed these traditional outcomes^{Reference Hollander, Blomkalns and Brogan19} and therefore reflect the concerns of physicians and the healthcare system, including costs. However, these outcomes do not reflect the patient's quality of life, including physical, emotional, and social states. A 60-year-old female with multiple cardiac risk factors, including a strong family history, may not be reassured by a 1-hour stay and a negative troponin, although it may be the medically “correct” approach. Conversely, an 88-year-old male referred from an extended care facility and with advanced dementia, with a chronically poor ejection fraction after remote bypass surgery, might medically benefit from additional testing resulting in another ACS diagnosis; however, this may not change overall management or ultimate outcome. Greater involvement of patients in decision-making has led to better outcomes including satisfaction,^{Reference Hess, Hollander and Schaffer20} and we encourage physicians to discuss goals and expectations with patients and caregivers before embarking on any particular diagnostic strategy.