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.

 

Stress Modes Stress Detection Modality
Exercise

– Treadmill or stationary bicycle25

– Increases cardiac demand

 

 

Vasodilation25

Adenosine, dipyridamole, regadenoson

– Increases coronary blood flow

 

 

Inotropy21,23-25

– Dobutamine

– Produces inotropic effects that increase cardiac demand and heart rate

ECG

– All modalities may employ ECG

– Most commonly used test

– Positive if the patient has early chest pain, hyper/hypotension, ST changes, or dysrhythmia

– Limited in patients with baseline abnormal ECG

Sensitivity 44-68%, Specificity 77%

 

Echocardiogram

– Used with exercise and inotropic stress test

Inducible wall-motion abnormalities highly sensitive for coronary artery disease (CAD), approaching 80%

– Disadvantages include operator dependence and technical limitations due to body habitus

 

MRI, PET, Radionuclide imaging

– Injectable radioisotope (Thallium201, Technetium99M) with imaging to evaluate myocardial perfusion at rest and with ischemic challenge (chemically induced or exercise)

Less operator dependent than other testing, sensitivity for stenosis approaches 90%

– More expensive and time consuming than other tests, also includes radiation exposure

Table 1: Stress Test Characteristics21-27

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

  1. Owens PL, Barrett ML, Gibson TB, Andrews RM, Weinick RM, Mutter RL. Emergency department care in the United States: a profile of national data sources. Ann Emerg Med 2010; 56:150–65.
  2. Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000; 342:1163–70.
  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.
  8. Freas GC. Medicolegal aspects of acute myocardial infarction. Emerg Med Clin North Am 2001;19(2):511–21.
  9. Rusnak RA, Stair TO, Hansen K, Fastow JS. Litigation against the emergency physician: common features in cases of missed myocardial infarction. Ann Emerg Med 1989;18(10):1029–34.
  10. Mitchell AM, Garvey JL, Chandra A, et al. Prospective multicenter study of quantitative pretest probability assessment to exclude acute coronary syndrome for patients evaluated in emergency department chest pain units. Ann Emerg Med 2006;47:447.
  11. Brooker JA, Hastings JW, Major-Monfried H, Maron CP, Winkel M, Wijeratne HR, et al. The Association Between Medicolegal and Professional Concerns and Chest Pain Admission Rates. Acad Emerg Med 2015 Jul;22(7):883-6.
  12. Buntinx F, Knockaert D, Bruyninckx R, de Blaey N, Aerts M, Knottnerus JA, Delooz H. Chest pain in general practice or in the hospital emergency department: is it the same? Fam Pract 2001 Dec;18(6):586-9.
  13. Venkatesh AK, Dai Y, Ross JS, Schuur JD, Capp R, Krumholz HM. Variation in U.S. Hospital Emergency Department Admission Rates by Clinical Condition. Medical care 2015;53(3):237-244.
  14. Canto JG, Shlipak MG, Rogers WJ, et al. Prevalence, Clinical Characteristics, and Mortality Among Patients With Myocardial Infarction Presenting Without Chest Pain. JAMA 2000;283(24):3223-3229.
  15. Kohn MA, Kwan E, Gupta M, Tabas JA. Prevalence of acute myocardial infarction and other serious diagnoses in patients presenting to an urban emergency department with chest pain. J Emerg Med 2005 Nov;29(4):383-90.
  16. Goldman L, Cook EF, Johnson PA, Brand DA, Rouan GW, Lee TH. Prediction of the need for intensive care in patients who come to the emergency departments with acute chest pain. N Engl J Med 1996 Jun 6;334(23):1498-504.
  17. Weinstock MB, Weingart S, Orth F, VanFossen D, Kaide C, Anderson J, Newman DH. Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission. JAMA Intern Med 2015 Jul;175(7):1207-12.
  18. van Ravesteijn H, van Dijk I, Darmon D, van de Laar F, Lucassen P, Hartman TO, van Weel C, Speckens A. The reassuring value of diagnostic tests: a systematic review. Patient Educ Couns 2012 Jan;86(1):3-8.
  19. Rolfe A, Burton C. Reassurance after diagnostic testing with a low pretest probability of serious disease: systematic review and meta-analysis. JAMA Intern Med 2013 Mar 25;173(6):407-16.
  20. Kline JA, Shapiro NI, Jones AE, Hernandez J, Hogg MM, Troyer J, Nelson RD. Outcomes and radiation exposure of emergency department patients with chest pain and shortness of breath and ultralow pretest probability: a multicenter study. Ann Emerg Med 2014 Mar;63(3):281-8.
  21. Anderson, JL, Adams, CD, Antman, EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 2007; 50:e1. https://www.ncbi.nlm.nih.gov/pubmed/17692738 
  22. Amsterdam EA, Kirk JD, Diercks DB, et al. Exercise testing in chest pain units: rational, implementation, and results. Cardiol Clin 2005;23:503–16.
  23. Hilton TC, Thompson RC, Williams HJ, et al. Technetium-99m sestamibi myocardial perfusion imaging in the emergency room evaluation of chest pain. J Am Coll Cardiol 1994;23:1016–22.
  24. Varetto T, Cantalupi D, Altieri A, et al. Emergency room technetium-99m sestamibi imaging to rule out acute myocardial ischemic events in patients with nondiagnostic electrocardiograms. J Am Coll Cardiol 1993;22:1804–8.
  25. Kosowsky JM. Approach to the ED patient with “low-risk” chest pain. Emerg Med Clin North Am 2011;29(4):721-727.
  26. Froelicher VF, Lehmann KG, Thomas R, Goldman S, Morrison D, Edson R, et al. The electrocardiographic exercise test in a population with reduced workup bias: diagnostic performance, computerized interpretation, and multivariable prediction. Ann Intern Med 1998;128(12):965-974.
  27. Mark DB, Shaw L, Harrell FE Jr, Hlatky MA, Lee KL, Bengtson JR, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med 1991 Sep 19;325(12):849-53.
  28. Prasad V, Cheung M, Cifu A. Chest Pain in the Emergency Department: The Case Against Our Current Practice of Routine Noninvasive Testing. Arch Intern Med 2012;172(19):1506-1509.
  29. Winchester DE, Brandt J, Schmidt C, Allen B, Payton T, Amsterdam EA. Diagnostic yield of routine noninvasive cardiovascular testing in low-risk acute chest pain patients. Am J Cardiol 2015 Jul 15;116(2):204-7.
  30. Hermann LK, Newman DH, Pleasant WA, Rojanasarntikul D, Lakoff D, Goldberg SA, Duvall WL, Henzlova MJ. Yield of routine provocative cardiac testing among patients in an emergency department-based chest pain unit. JAMA Intern Med 2013 Jun 24;173(12):1128-33.
  31. Scheuermeyer FX, Innes G, Grafstein E, Kiess M, Boychuk B, Yu E, Kalla D, Christenson J. Safety and efficiency of a chest pain diagnostic algorithm with selective outpatient stress testing for emergency department patients with potential ischemic chest pain. Ann Emerg Med 2012 Apr;59(4):256-264.e3
  32. 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):428-436.
  33. Walker J, Galuska M, Vega D. Coronary disease in emergency department chest pain patients with recent negative stress testing. West J Emerg Med 2010;11:384-388
  34. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 2013;368(21):2004-3.
  35. Arbab-Zadeh A, Nakano M, Virmani R, et al. Acute coronary events. Circulation 2012;125(9):1147-56.
  36. Virmani R, Burke AP, Farb A, et al. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006;47(8):C13-8.
  37. Gibler WB, Runyon JP, Levy RC, Sayre MR, Kacich R, Hattemer CR, A rapid diagnostic and treatment center for patients with chest pain in the emergency department. Ann Emerg Med 1995 Jan;25(1):1-8.
  38. 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 Jul 17;40(2):251-6.
  39. Mallidi J, Penumetsa S, Friderici JL, Saab F, Rothberg MB. The effect of inpatient stress testing on subsequent emergency department visits, readmissions, and costs. J Hosp Med 2013 Oct;8(10):564-8.
  40. Penumetsa SC, Mallidi J, Friderici JL, Hiser W, Rothberg MB.. Outcomes of patients admitted for observation of chest pain. Arch Intern Med 2012 Jun 11;172(11):873-7.
  41. Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-16.
  42. 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 Int Med 2012 Feb;172(4):312.
  43. 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):232-240.
  44. Lai C, Noeller TP, Schmidt K, King P, Emerman CL. Short-term risk after initial observation for chest pain. J Emerg Med 2003;25(4):357-362.
  45. Shaver KJ, Marsan RJ Jr, Sease KL, Shofer FS, Sites FD, Hollander JE. Impact of a negative evaluation for underlying coronary artery disease on one-year resource utilization for patients admitted with potential acute coronary syndromes. Acad Emerg Med 2004 Dec;11(12):1272-7.
  46. Barraclough K, Gale CP, Hall R. Assessment of chest pain in a low risk patient: is the exercise tolerance test obsolete? BMJ 2015 May 6;350:h190

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