Chest Pain Controversies: Risk Stratification and Stress Test Utility (Part 1)

Authors: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) // Edited by: Jamie Santistevan, MD (@Jamie_Rae_EMdoc, Admin and Quality Fellow at UW, Madison, WI)

 A 53-year-old female presents with 5 hours of chest pain and diffuse weakness. She denies dyspnea, nausea/vomiting, and diaphoresis. Her vital signs, ECG, chest X-ray, and initial labs are completely normal, including troponin and TSH. You have low suspicion of PE, dissection, and other life-threatening diseases. What is her risk for ACS and adverse cardiac events? What is the utility of stress testing?

Chest pain accounts for approximately 8-10 million healthcare visits in the U.S. per year, with 10% of ED visits and 25% of hospital admissions due to chest pain.^1-6 Chest pain can be associated with benign to life-threatening diseases, and heart disease is one of the major considerations in the ED.^1,5,6

The American Heart Association (AHA) supports noninvasive cardiac imaging for further evaluation before or within 72 hours of discharge.⁶ However, there is no evidence that stress testing decreases risk of future cardiac events. Multiple options for noninvasive testing exist, each with specific advantages and disadvantages. This post is the first of a two-part series evaluating chest pain controversies. This post will examine chest pain risk stratification in the ED and the utility of stress testing.

The Risk of Chest Pain and Missed ACS

The evaluation of chest pain can lead to multiple issues: prolonged ED stays, provocative testing, and anxiety for the patient and physician. Approximately 20% of lawsuits are due to misdiagnosis and mismanagement of acute coronary syndrome (ACS). Missed myocardial infarction (MI) has mortality rates ranging from 10% to 25% for patients discharged home.^2,7-9

Physicians admit a large percentage of patients with chest pain due to this risk.¹¹ However, few admitted patients go on to be diagnosed with ACS.¹⁰ Over-testing can lead to false positives, further downstream testing, and potential patient harm. The true rate of misdiagnosis is close to 0.2%, rather than the commonly quoted 2% from the Pope et al. study in 2000.² Goldman et al. suggested patients without hypotension, heart failure, known prior myocardial infarction, or worsening chest pain have less than 1% risk of death, need for revascularization, or ACS.¹⁵ Weinstock et al. in 2015 found that with two negative troponin tests and a non-ischemic ECG, the primary outcome of adverse cardiac event occurred in 0.18% of admissions.¹⁷

Despite what many think, further testing does not necessarily lead to patient reassurance. One study evaluating patients with complaints including chest pain found patients receiving more testing are in the short term more satisfied, but at long-term follow up, patient outcomes and satisfaction do not differ.¹⁸ Rather than more testing, addressing patient concerns and fears is paramount. A separate study found further diagnostic testing does not affect patient symptoms, anxiety, or concerns in the short or long term.¹⁹ There are also harms associated with further testing including iatrogenic injury and increased radiation exposure.²⁰

What is the Utility of Stress Testing?

Several noninvasive cardiovascular testing modalities allow further evaluation of patients with chest pain, evaluating for obstructive coronary artery disease (CAD) and inducible angina. Per the AHA, stress testing in low to intermediate risk chest pain patients within 72 hours increases sensitivity and negative predictive value (NPV) of short term death or MI.^6,21 The two main components of stress testing include stress mode and stress detection. Many of these modalities are institution-dependent. These modalities are shown in Table 1 below.

Table 1: Stress Test Characteristics^21-27

A Little History Lesson…

Stress tests were first used before the 1960s. Froelicher in 1998 conducted one of the first large evaluations, where 814 patients underwent both exercise testing and coronary angiography. Standard exercise stress test demonstrated sensitivity of 45% and specificity of 85%.²⁶ Mark in 1991 utilized exercise treadmill test to identify patients with different degrees of mortality risk from cardiovascular events and found a treadmill score to be better than clinical assessment.²⁷

Stress testing use tripled in the early 2000’s due to feasibility.²⁸ Providers began to use the test to risk stratify; however, the test was designed to detect fixed obstruction, not to provide risk stratification.²⁵ Risk stratification became increasingly important with the risk of missing ACS and MI.^2,7-9 However, the risk of ACS approaches less than 1% after two negative troponins and normal ECG. This number already places patients at low-risk for adverse events, which makes it difficult to risk stratify further.^2,17,25

One study demonstrated a diagnostic yield of 2.5% of patients undergoing testing, with a low positive predictive value.²⁹ This 2015 study found that patients with abnormal tests did not differ in outcomes when compared to those with normal testing.²⁹ A 2013 study found a 11.2% positive test rate, and only one fourth of these patients underwent angiography. Furthermore, only 0.7% would benefit from revascularization.³⁰ Scheuermeyer evaluated stress testing in the use of a diagnostic algorithm comparing outpatient testing, admission, and brief observation. Biomarkers found all MI’s, with no assistance from stress tests.³¹ Foy in 2015 conducted a retrospective analysis evaluating patients with chest pain classified into 5 separate testing strategies: no testing, exercise stress, stress echocardiogram, myocardial perfusion scan, and CCTA.³² In the study population, 0.11% of patients at 7 days and 0.33% of patients at 190 days experienced MI. Investigators suggested patients undergoing no testing do not experience any difference in rate of MI when compared to patients undergoing testing.³² Patients with positive tests underwent further intervention, with greater risk due to iatrogenic injury.³²

Does it risk stratify?

Many providers rely on a negative stress test to decrease their concern for ACS.²⁵ However, stress tests are limited in determining the risk of future ACS, as 5% to 15% of patients presenting to the ED with a negative stress test in the last three years will have positive cardiac markers, cardiac catheterization, or death due to cardiac arrest within 30 days of their ED visit.^25,33 These tests are designed to diagnose fixed obstruction, not to risk stratify. A recent NEJM study suggested that plaque vulnerability is dependent on the presence of a fibrous covering, lipid core, and inflammatory cells.³⁴ Plaques with these factors are more unstable and rupture at higher rates, while often not obstructing more than 60% of the lumen. Stress testing may not diagnose these dangerous, but non-obstructing plaques, which can grow into the vessel wall.^34-36 Rather, endovascular US may be needed.

Does it diagnose ACS?

Stress testing diagnosis of ACS is also limited.²⁵ Gibler in 1995 evaluated 1010 patients with serial testing of CK-MB, ECG monitoring, and echocardiogram with graded exercise testing.³⁷ Twelve patients experienced MI, and all patients were biomarker positive.³⁷ Amsterdam in 2002 evaluated approximately 1000 patients with nonspecific ECG and immediate stress testing.³⁸ Five patients had MI, all with positive biomarkers. Stress testing missed one patient. Other studies demonstrate a similar result in that biomarkers diagnose MI, which may be missed by stress testing.³⁸ Noninvasive cardiac testing also does not change revisit or hospital admission rates.³⁹

Even with a positive stress test, patients do not always undergo further testing or intervention. One study found that 90% of patients with positive stress test received no further testing or intervention.⁴⁰ In the COURAGE trial, patients with positive stress tests randomized to revascularization versus medical treatment demonstrated no change in mortality, nonfatal MI, nonfatal stroke, or ACS hospitalization.⁴¹ Stergiopoulos et al. also found no benefit to invasive therapy plus medical therapy compared to medical therapy alone after a positive stress test in two separate meta-analyses.^42,43

Patients with low risk chest pain and negative ECG and biomarkers may be discharged with follow up.^25,44 Further testing during admission does not change hospital admission rates on second visit, rates of further stress testing, and rates of catheterization.⁴⁵ A low risk of cardiac events was found no matter the disposition of the patient or further evaluation with noninvasive testing. Literature suggests stress testing should be avoided for use as a diagnostic tool and a marker for the need of further intervention.⁴⁶ Stress testing may assist in prognostication over long term, but it lacks the ability to make the acute diagnosis of ACS and to risk stratify.^25,44-46

 Summary

– Missed ACS is a concern for patients and emergency providers.

– Misdiagnosis and mismanagement of ACS accounts for a large percentage of lawsuits. However, the true rate of missing ACS approaches 0.2%.

– Nonischemic ECG and negative biomarker at 0 hr and 3 hr reduces risk of MACE to less than 1%.

– Further testing does not provide reassurance. Discussion with the patient of the assessment and follow up plan is needed.

– Stress testing can be conducted with several modes and modalities which perform similarly, but these evaluations cannot further risk stratify patients to less than 1% risk.

– Stress testing does not diagnose MI or ACS.

References/Further Reading

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3. Pines JM, Isserman JA, Szyld D, Dean AJ, McCusker CM, Hollander JE. The effect of physician risk tolerance and the presence of an observation unit on decision making for ED patients with chest pain. Am J Emerg Med 2010; 28:771–9.
4. Fleischmann KE, Goldman L, Johnson PA, et al. Critical pathways for patients with acute chest pain at low risk. J Thromb Thrombolysis 2002; 13:89–96.
5. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation 2011; 123:e18–e209.
6. Amsterdam EA, Kirk JD, Bluemke DA, et al; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Cardiovascular Nursing, and Interdisciplinary Council on Quality of Care and Outcomes Research. Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. Circulation 2010;122(17):1756-1776.
7. McCarthy BD, Beshansky JR, D’Agostino RB, et al. Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study. Ann Emerg Med 1993;22(3):579–82.
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