I. Problem/Challenge.

Cardiac stress tests serve the purpose of diagnosis as well as prognosis of those who have symptoms compatible with myocardial ischemia. They are also used for prognosis in those known to have ischemic heart disease.

The clinical gold standard for the diagnosis of coronary artery disease (CAD) remains the coronary angiogram. This is costly, invasive, requires expertise and is associated with the minor but significant risk of bleeding and contrast nephropathy. The prognosis of CAD is dependent on the amount of left ventricle that is burdened, which is in turn dependent on the anatomy of the coronary vasculature. The more vessels that are involved and the more proximal the lesion is, the greater is the risk of adverse cardiovascular events.

Stress testing serves the purpose of non-invasively determining which patients have a high enough risk of adverse cardiovascular events to have a mortality benefit from revascularization. It can also determine the physiologic significance of a flow-limiting lesion whereas angiography provides a static assessment of a stenotic lesion.

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II. Identify the Goal Behavior

The first step in the assessment of a patient with symptoms suggestive of myocardial ischemia is the clinical assessment of pretest probability. Making a determination of the likely prevalence of CAD in a patient will direct the decision to further risk stratify with stress testing. The pretest probability, or Bayesian probability, uses the history, physical exam, electrocardiogram (ECG), and cardiac biomarkers and is crucial in assessing the result of a stress test.

The next step is the selection of the type of stress test, including exercise or pharmacologic stress along with myocardial perfusion imaging, echocardiography, cardiac computed tomography (CT), or cardiac magnetic resonance imaging (MRI). Selection of the most appropriate test is based on a combination of patient factors, initial ECG and local institution factors. The last step is to determine the post-test probability of disease and if angiography or medical management is appropriate.

III. Describe a Step-by-Step approach/method to this problem.

The evaluation of patients presenting with chest pain that is suspected to be due to CAD should have an initial assessment of the likelihood of disease. Multiple large cohort studies have demonstrated that patient’s age, gender, cardiac risk factors, and characterization of the chest pain can estimate the probability of disease. It is important to remember that these cohorts were derived from referral populations, which may have a higher prevalence of disease and thus these models may overestimate the pretest probability.

Characterization of the chest pain is based on three questions:

  • Is the pain retrosternal?

  • Is it reliably brought on by exertion or emotional stress?

  • Is it reliably relieved within minutes of resting or sublingual nitroglycerin?

Typical angina is defined as the presence of a positive answer to all three questions. Atypical angina is the presence of two positive answers. Non-anginal chest pain is the presence of one or none of the factors. The type of chest pain can then be combined with the patient’s age and sex to generate a pretest probability. SeeTable I

For the purpose of diagnosis, only those patients who fall in the intermediate pretest probability (i.e. more than 10% but less than 90%) should be tested, since it is only this group of patients in whom a positive or a negative stress test will make a significant post-test change in the probability of significant CAD.

The American College of Cardiology and American Heart Association (ACC/AHA) 2002 guidelines do not recommend routine testing for those patients with low pretest probability as the positive predictive value of an abnormal test is only 21%.

Inpatients who present with acute chest pain but with symptoms suggestive of “intermediate probability” for acute coronary syndrome (ACS) should undergo stress testing for the purpose of diagnosis. As per the ACC/AHA guidelines, this should be done within 72 hours of presentation and it may be done as an outpatient if arrangements can be made reliably.Those patients who have a high pretest probability based on the presentation may be referred for coronary angiogram or may undergo stress testing to determine prognosis. A negative stress test in these patients does not rule out CAD, however it portends a relatively good prognosis.

There are two considerations in choosing a stress test. First, what will be the type of stress used: exercise or pharmacologic? Second, what testing modality should be used: electrocardiography or imaging (echocardiography or nuclear perfusion)?

Imaging based testing offers the advantage of localizing ischemia and assessing myocardial viability. Exercise stress provides additional information beyond pharmacologic stress and should be chosen unless contraindicated or the patient is unable.

Exercise increases demand of myocardial oxygen and changes in ECG or anginal symptoms correlate with myocardial ischemia. Exercise capacity and the hemodynamic response to exercise are predictive of prognosis independent of ischemia. The inability to exercise is also associated with a higher cardiovascular risk. Standard exercise ECG testing is preferred if a patient can exercise and has no baseline ECG abnormalities (except for right bundle branch block or less than 1mm ST depression), is not on digitalis therapy and has not had previous revascularization.

In the presence of significant baseline ECG abnormalities, digitalis therapy or previous revascularization, exercise stress imaging should be performed. If a patient cannot exercise, pharmacologic stress should be used in place of exercise. Local expertise or availability will also influence the test choice.

There is limited research comparing the different stress testing modalities directly. One study compared exercise ECG testing, dobutamine-atropine echocardiography, dipyridamole echocardiography, and radionuclide myocardial perfusion imaging with technetium-99m sestamibi with dobutamine stress. These four tests had similar positive predictive values but the imaging modalities had greater negative predictive value than standard exercise ECG testing.

One meta-analysis compared several modalities of pharmacologic stress testing. Angiographic data was compared to echocardiography or nuclear perfusion studies using adenosine, dipyridamole or dobutamine. Adenosine and dipyridamole perfusion imaging had the best negative likelihood ratio with adenosine being slightly better. Echocardiography is more operator dependent and affected by pulmonary disease than are the nuclear imaging modalities.

Table I.
Asymptomatic Non-anginal chest pain Atypical angina Typical angina
Age Male Female Male Female Male Female Male Female
30-39 1.9 0.3 5.2 0.8 21.8 4.2 69.7 25.8
40-49 5.5 1.0 14.1 2.8 46.1 13.3 87.3 55.2
50-59 9.7 3.2 21.5 8.4 58.9 32.4 92.0 79.4
60-69 12.3 7.5 28.1 18.6 67.1 54.4 94.3 90.6

IV. Common Pitfalls.

It is important to remember that chest pain can represent a serious non-cardiac condition. Keep in mind a broad differential and allow initial impressions to change as you gather information. Pulmonary embolism, aortic dissection, pneumothorax, cardiac valvular disease, esophageal disorders, and peptic ulcer disease can mimic angina.

Diagnosing CAD in women is challenging. Women are less likely to present with typical angina. False positive test results during exercise ECG testing are more common in women possibly owing to a lower prevalence of coronary disease than in men of the same age.

It is important to remember that patients who present with definite ACS, such as ST segment elevations, other ECG changes suggestive of a non-ST segment elevation myocardial infarction (MI) or unstable angina with high risk features (ST depressions, prior history of MI, significant change in prior symptoms of stable angina, or initially positive cardiac biomarkers) benefit from prompt coronary angiography and appropriate revascularization.

Recognition of any of these factors should prompt immediate cardiology consultation, transfer to a facility with interventional cardiology capabilities or consideration of thrombolysis.

V. National Standards, Core Indicators and Quality Measures.

Recent advances in medical therapy for CAD highlight the importance of aggressive risk factor modification. Recent trials have shown equivalent outcomes between revascularization and optimal medical therapy in certain populations. In light of this, appropriate screening and treatment of lipid disorders, blood pressure and diabetes, as well as antiplatelet therapy for secondary or primary prophylaxis are crucial.

VI. What's the evidence?

San Roman, JA, Vilacosta, I, Castillo, JA. “Selection of the optimal stress test for the diagnosis of coronary artery disease.”. Heart. vol. 80. 1998. pp. 370

Gibbons, RJ, Balady, GJ, Bricker, JT. “ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines).”. Circulation. vol. 106. 2002. pp. 1883

Fleisher, LA, Beckman, JA, Brown, KA. “2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for non-cardiac surgery: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines”. Circulation. vol. 120. 2009. pp. e169

Kim, C, Kwok, YS, Heagerty, P, Redberg, R. “Pharmacologic stress testing for coronary disease diagnosis: A meta-analysis.”. Am Heart J. vol. 142. 2001. pp. 934

Diamond, GA, Forrester, JS. “Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease.”. N Engl J Med. vol. 300. 1979. pp. 1350