Chest pain is a common diagnosis in primary care and outpatient cardiology settings and leads to between 8 and 10 million ED visits annually in the US.1 Differentiating ischemic causes from nonischemic causes can be difficult because patients with chest pain with an ischemic etiology often appear well.2 Therefore, the initial diagnostic approach should always consider a cardiac etiology until proven otherwise.2
A common feature of ischemic cardiac pain is pressure-type chest pain that occurs with exertion or at rest that lasts more than 10 minutes.3 Patients may report pain beginning in the retrosternal area with radiation to either one arm or both arms, the neck, jaw, or throat.3 Other symptoms may include dyspnea, diaphoresis, nausea, vomiting, abdominal pain, or syncope. An ECG can determine if any ST segment changes are present that would indicate myocardial ischemia, infarction, or injury. If these changes are present, the patient should be immediately referred to the ED.
The evaluation of chest pain has many differential diagnoses. Nonischemic causes, such as gastroesophageal reflux, pulmonary embolism, aortic dissection, pneumonia, and musculoskeletal pain, may be high on the differential list. A detailed history and comprehensive physical exam must be obtained to determine which diagnostic test is most appropriate for the individual patient's chest pain evaluation.4 This article will assist the primary care NP in decision-making regarding appropriateness of stress testing and will provide information regarding the process, interpretation, limitations, risks, and benefits of testing.
When to test
Stress testing is a noninvasive, convenient way to assess for exercise-induced myocardial ischemia. The overall goal of stress testing is to determine whether a mismatch of oxygen supply and demand exists. The American Heart Association (AHA) Scientific Statement for Exercise Standards for Testing and Training lists several purposes for exercise testing.5 (See Purposes of exercise testing.)
In outpatient practice, stress testing is ordered for patients who are having chest pain with features that can either be typical or atypical for angina. These patients may or may not have risk factors for coronary artery disease (CAD) such as diabetes mellitus, hypertension, hyperlipidemia, or smoking. For instance, a younger patient (age 40 or younger), with a family history of CAD and atypical chest pain would be a candidate for an exercise treadmill test (ETT), also known as an exercise tolerance test.5
For patients with risk factors alone, stress testing may be ordered for further risk stratification. Stress testing is appropriate for patients only complaining of shortness of breath, which may be an anginal equivalent, and to rule out a cardiac etiology prior to pulmonary evaluation. During preoperative evaluation, stress testing is ordered to determine cardiac risk stratification and can be used to assess a patient's functional capacity or exercise tolerance prior to beginning a cardiac rehab program. In outpatient cardiology practice, stress testing may be ordered every 2 to 3 years for patients with CAD as surveillance of disease progression.
Patients experiencing palpitations are often ordered an ETT to assess for dysrhythmias (such as ventricular tachycardia or premature ventricular contractions) during exercise. An ETT may also be appropriate for stable, younger patients with CAD who maintain regular physical activity. Stress tests are often undertaken for truck drivers who require annual US Department of Transportation evaluation. In addition, patients presenting to the ED with chest pain for whom acute coronary syndrome has been ruled out may have an ETT ordered in the outpatient setting.
For each stress test ordered, there is a different level of predictive value, which is influenced by the prevalence of disease in the group or individual being tested.5 Bayes' theorem states that the pretest probability of disease affects the posttest probability, so the group studied affects the test accuracy. Therefore, age, gender, symptoms, and other known risk factors are included in the test dataset to improve result analysis.5 Increased cardiac risk factors correspond to a higher pretest probability of CAD.
The AHA Scientific Statement for Exercise Standards for Testing and Training contains absolute and relative contraindications to exercise testing.5 (See Absolute and relative contraindications to exercise testing.) These contraindications serve to balance the test's potential risks and benefits. Patients must be routinely screened for any contraindications by the ordering provider and reviewed again at the time of testing.
Good clinical judgment must always be foremost in decision-making regarding the appropriateness of exercise testing. Testing may be cancelled when patients show evidence of decompensated heart failure, uncontrolled hypertension, hypotension, unstable angina, new-onset atrial fibrillation with rapid ventricular response, upper respiratory infection, or heart block. The test is rescheduled after the patient's clinical condition has stabilized, and the test can be safely undertaken. Written informed consent should always be obtained, and the clinician should ensure that the patient understands the risks and benefits of the test.5
Exercise treadmill tests
The simplest stress test and starting point of evaluation is a basic ETT. Treadmill testing is readily available in the outpatient setting, and there is very little patient preparation regarding dietary and medication restrictions. The only requirement is that the patient wear comfortable, loose-fitting clothing and proper footwear.
Treadmill testing is the preferred mode of stress testing used in the US, although stationary cycle ergometry is an alternative method.6 A common exercise stress test protocol is the Bruce protocol.7 The test begins with the treadmill set to a low speed (1.7 mph) and a 10% incline. For patients unable to tolerate the Bruce protocol, there is a modified Bruce protocol that provides a lower workload for patients with poor cardiovascular fitness.7 The speed and angle of the treadmill for the Bruce protocol are increased every 3 minutes. BP and ECG are monitored before, during, and after the test. ETTs can determine exercise capacity, which is one of the strongest indicators of long-term risk (including death) for those with suspected and known CAD.8 For this reason, ETT is the preferred stress test for individuals who can exercise and achieve the predicted target heart rate.9
In order to elicit any ECG changes associated with ischemia, the patient needs to reach 85% of a predetermined age-related heart rate.9 One commonly used formula defines an adequate achieved heart rate as 85% of the difference between 220 and the patient's age.5 If the test is being performed to diagnose ischemia and the patient is taking a beta-blocker or calcium channel blocker, those medications may be held for 24 to 48 hours prior to the test to increase the likelihood that an adequate heart rate and BP are achieved. The ordering provider may also request a stress test with the patient continuing to take these medications to determine adequacy for exercise or cardiac rehabilitation.
ETTs or nuclear ETTs (an ETT with nuclear capability) may be inappropriate for patients with limited ability to walk because of orthopedic or physical disability. If the patient has an abnormal baseline ECG, such as a left bundle-branch block (LBBB), left ventricular hypertrophy (LVH) with repolarization abnormalities, or a ventricular paced rhythm, this test will limit the ability to assess for ST segment changes during exercise and would not be appropriate.7 (See Sample LBBB and Sample LVH.) Therefore, obtaining a baseline 12-lead ECG before ordering a stress test is vital so that the most appropriate test is ordered. If a patient has an implanted defibrillator, the settings should be known, and the upper rate should not be exceeded during testing.
The AHA Scientific Statement of Exercise Standards for Testing and Training lists absolute and relative indications for termination of exercise testing based on patient's worsening symptoms, evidence of ischemia, a drop in systolic BP, signs of poor perfusion, dysrhythmias, exaggerated hypertension (BP greater than 250/115 mm Hg), patient safety issues, or the patient's request to stop.5
Adverse events from exercise testing are rare during properly supervised tests.7 Death occurrence is estimated at 1 per 10,000 tests or fewer.5 There is approximately one cardiac arrest per 565,000 person-hours of exercise for the general population.7 For those with known CAD, there is an estimated 1 arrest per 59,000 person-hours of vigorous exercise.7 Other complications that can occur are bradydysrhythmias, tachydysrhythmias, acute myocardial infarction (approximately 1.4 per 10,000 exercise tests), heart failure, hypotension, syncope, and shock.5,7
Nuclear stress tests
A nuclear stress test is an ETT with myocardial perfusion imaging (MPI). It should be ordered when there are resting ECG abnormalities as previously stated that limit the accurate interpretation of the ECG and reduce test accuracy.8 A nuclear stress test may be ordered during the initial patient evaluation when it is determined that high probability exists for heart disease because of patient risk factors and symptoms. An example would be a patient presenting with exertional dyspnea with risk factors. In addition, patients with abnormal, equivocal, or indeterminant ETT results are typically referred for nuclear exercise stress testing. Nuclear imaging is contraindicated for patients who are pregnant. Women of childbearing age must obtain a pregnancy test prior to a scheduled nuclear stress test.
Stress MPI can be performed as single-photon emission computed tomography (SPECT) or as positron emission tomography (PET).5 According to the AHA Exercise Standards for Training and Testing, SPECT is more widely available and technically less challenging than PET, with a better established diagnostic and prognostic value of SPECT.5 The MPI agents used in practice today along with SPECT or PET are technetium (Tc-99m) tetrofosmin (Myoview) and Tc-99m sestamibi (Cardiolite).5 Both of these radiotracers have good safety profiles with two to six adverse events per million injections.10 Radiation exposure from a nuclear stress test is approximately 512 times more radiation than an anterior-posterior chest radiograph.11 The risks of radiation exposure must always be weighed against the benefits of testing.
The added benefit of MPI significantly improves sensitivity and specificity over standard ETT. For the general population, the sensitivity of ETT is 68% and the specificity is 70%.7 Values are lower for patients at low risk, and ETT has a higher sensitivity and specificity for individuals at high risk.7 The average sensitivity of SPECT with technetium 99m for detecting flow-limiting coronary stenosis is 90% and the average specificity is 74%.7
The radiotracer is injected at the beginning of the nuclear stress test prior to resting images and again during the stress portion of the test (drug infusion or exercise). Following the stress portion of the test, resting images and stress images are compared to determine if perfusion deficits exist because of disproportionate blood flow. These images are interpreted by physicians who have received specific training in nuclear cardiology. Perfusion defects that present during exercise, but not at rest, indicate myocardial ischemia (also called reversible defects).5 Perfusion defects that present during exercise that persist at rest (also called nonreversible or fixed defects) can represent scar, hibernating myocardium, or attenuation artifact.7 Differentiating between the two is paramount.7 MPI also provides ejection fraction analysis and regional wall motion abnormalities. Patients with abnormal nuclear stress tests are often referred for coronary angiography.
Pharmacologic stress tests
Pharmacologic stress tests are ordered for patients with baseline ECG abnormalities who are unable to exercise adequately. Examples include deconditioning, neurologic issues, peripheral vascular disease, and orthopedic disabilities.5 A pharmacologic test should be ordered if there is uncertainty about the patient's ability to walk safely on a treadmill. Pharmacologic stress tests are limited in that they deprive the provider of valuable test information, such as functional capacity, symptom status with exercise, and heart rate and BP response.12 These factors have been strongly predictive of cardiac events and mortality. Pharmacologic stress tests require the use of MPI and take approximately 3 to 5 hours to complete. An increase in the pharmacologic stress test prevalence can be attributed in part to the aging population and obesity epidemic.
During pharmacologic stress tests, vasodilating agents, such as regadenoson (Lexiscan), adenosine, and dipyridamole (Persantine), are administered to simulate the effects of exercise. These agents cause coronary vasodilatation in normal epicardial arteries by stimulation of the adenosine A2A receptor.5,13 When administered, coronary arteries with significant stenoses cannot increase coronary flow as much as coronary arteries without stenoses. The lack of increased perfusion during vasodilation can be visualized when combined with nuclear MPI.5
Adverse reactions associated with these agents include headache, flushing, chest pain, nausea, dyspnea, and atrioventricular (AV) block.5 Chest pain can be an adverse reaction and is nondiagnostic for ischemia. Regadenoson is better tolerated than adenosine or dipyridamole and has a significantly lower incidence of adverse reactions in patients with obstructive airway disease.10,13 Patients must refrain from consuming caffeine (and medications that are xanthine derivatives) at least 12 hours prior to the study because caffeine can potentially blunt the vasodilator effect and cause false-negative test results.13 In addition, patients should refrain from eating for at least 3 hours prior to the test.
Contraindications to receiving pharmacologic agents are severe restrictive or bronchospastic pulmonary disease, asthma with ongoing wheezing, second- or third-degree AV block without a pacemaker, sick sinus syndrome, systolic BP less than 90 mm Hg, recent use of dipyridamole-containing medications, known hypersensitivity to dipyridamole, recent caffeine ingestion, unstable acute myocardial infarction, or acute coronary syndrome.14
Stress echocardiography is another stress testing method that combines exercise or dobutamine with echocardiography to determine left ventricular function and the presence of ischemia.9 Following resting echocardiographic images, the patient performs an ETT attempting to achieve at least 85% of his or her peak maximum age-related heart rate. Echocardiographic images are repeated immediately after exercise. The pretest and posttest images are compared side by side to evaluate for areas of ischemic myocardium, which would manifest as hypokinesis, akinesis, or dyskinesis of the left ventricle on the images.5
A test is considered positive if a regional wall motion abnormality develops with exercise in normal functioning resting myocardium or worsens in baseline abnormal segments.5 Difficulty obtaining an echocardiographic window or poor image quality can limit the diagnostic accuracy of this test, particularly in patients who are obese or have obstructive lung disease.5 The sensitivity of stress echocardiography for identifying flow-limiting coronary stenosis greater or equal to 50% varies from 68% to 98%, and specificity ranges from 44% to 100%.7 This test is appropriate as a substitute for nuclear MPI in patients who can exercise.
Interpretation of test results
Heart rate should increase with exercise and should continue to rise with higher workloads because of decreased vagal tone followed by increased sympathetic outflow.5 A patient is considered to have chronotropic incompetence if he or she does not achieve greater than 85% of his or her maximum age-predicted heart rate with exercise while not taking a heart rate-limiting drug.5 In patients with known cardiovascular disease, chronotropic incompetence is associated with increased mortality and is a marker for sinus node disease.5 Chronotropic impairment has been shown to occur with increased frequency in patients with diabetes mellitus (likely because of autonomic dysfunction), and is greater among those with neuropathy.5 When exercise is terminated, heart rate recovery tends to be greater in the first 30 seconds because of vagal reactivation. Following this phase, there is a slower return to the preexercise level. A decline in heart rate from peak exercise of 12 beats or less 1 minute after exercise cessation while in the upright position defines an abnormal heart rate recovery response.5
Average BP response during exercise testing is an increase of approximately 10 mm Hg per exercise stage.5 Systolic BP response is dependent on gender (higher in males) and age (higher with advancing age).6 A poorer prognosis is associated with BP that fails to elevate with exercise or that falls from resting level.6 Poor BP response can be attributed to aortic outflow obstruction, myocardial ischemia, severe left ventricular dysfunction, or left main or triple vessel CAD.6 A normal diastolic BP response is for diastolic BP to remain about the same or to decrease to even a moderately lower level (because of vasodilatation of the vascular bed).5
Hypertensive individuals tend to have an exaggerated BP response, even with normal resting BP prior to exercise. An exaggerated BP response may be indicative of an increased risk of future hypertension, cardiovascular events, or LVH.5 Systolic BP typically decreases at least 15% by 3 minutes postexercise and may remain below the preexercise level for several hours after testing.15
The ECG is monitored for exercise-induced ST segment depression, which is the most common manifestation of exercise-induced myocardial ischemia.6 An abnormal response or positive test result is horizontal or downsloping ST segment depression greater than or equal to 1 mm or more for 0.8 seconds in three consecutive beats.6 Downsloping ST depression is more specific for ischemia than horizontal or upsloping, and at a low level of exercise, downsloping ST depression has a worse prognosis and is most likely related to multivessel CAD.6 The longer ST depression persists into recovery can be related to the severity of CAD.6 The degree, time of appearance, duration, and number of leads with ST-segment depression are related to the probability and severity of CAD.6 ST depression can also occur in patients who are taking digoxin and is not diagnostic for ischemia in this patient population. (See Sample ECG of horizontal ST depression indicative of myocardial ischemia.)
Exercise can both suppress and induce cardiac dysrhythmias.5 In the presence of CAD, exercise-induced myocardial ischemia can predispose the patient to ectopic activity.5 The most frequent cardiac dysrhythmias during exercise are ventricular ectopic beats.5 Their prevalence is directly related to age and cardiac abnormalities, including cardiomyopathy, valvular heart disease, or severe myocardial ischemia, and a family history of sudden cardiac death.5 Ventricular ectopy in recovery is a better predictor of death than ventricular ectopy during exercise.7 Supraventricular dysrhythmias induced by exercise are not usually associated with CAD but can be a result of age, pulmonary disease, recent alcohol ingestion, or excessive caffeine intake.5 Atrial fibrillation and atrial flutter induced by exercise occur in less than 1% of those undergoing stress testing.5
Conduction system abnormalities can both develop and disappear during exercise.5 Development of LBBB with exercise prevents the diagnosis of ischemia from the ECG. LBBB that develops during exercise may or may not be associated with CAD but does predict higher risk of death and major cardiac events.5 Right bundle-branch block occurs less often with exercise than LBBB in patients with high prevalence of heart disease but can be associated with underlying CAD affecting the left anterior descending artery.5 The development of bundle-branch blocks may be related to heart rate. Second-degree AV block during exercise is usually associated with CAD or aortic stenosis.5 Although rare, third-degree AV block can be induced by exercise and is likely related to transient ischemia. Development of LBBB during an ETT would be reason for termination of the test as diagnosis of myocardial ischemia is usually impossible when LBBB is present.5 In addition, advanced or complete AV block are criteria for termination of stress testing.5
False-positive and false-negative results
False-positive or false-negative test results can be considered limitations of stress testing. As mentioned, digoxin can produce a false-positive result characterized by ST segment depression that becomes more pronounced with exercise.16 LVH may produce a similar result. Causes of false-positive perfusion study results include attenuation defects such as breast or diaphragm attenuation. Attenuation artifacts are considered to be one of the most significant limitations to MPI SPECT imaging.17 Breast attenuation can affect the anterolateral, septal, and anteroseptal walls of the ventricle and may show decreased radiotracer activity leading to interpretation of a perfusion defect.7 Diaphragmatic attenuation may lead to interpretation of a perfusion defect of the inferior and inferolateral walls.7 A positive nuclear stress test may lead to further diagnostic testing with associated costs and risks.
A false-negative exercise result in patients with CAD may be caused because of nitrate therapy that allows patients to exercise for longer and show less ST ischemic changes during exercise than would otherwise be present in the absence of nitrate therapy. Beta-blockers can produce a false-negative result if the patient is not achieving an adequate heart rate necessary to potentially cause ischemia. In addition, a test that is terminated prior to the patient exercising to a sufficient workload for any reason may produce a false-negative result. Balanced coronary stenoses or balanced ischemia is another example of a clinical situation that can cause a false-negative result. It has been associated with multivessel disease and involves the electrical cancellation of the ischemic ST-segment vectors because of severe ischemia.18 These patients may have false-negative SPECT scans as the radiotracer uptake by the different myocardial regions becomes homogenously distributed because of globalized hypoperfusion in all the segments of the myocardium.18
Stress testing is a valuable diagnostic tool used in the evaluation of chest pain that can provide information as to whether symptoms may have a cardiac etiology. The key is not to consider the results in isolation but to make them useful components of a decision-making process. It is important to advise patients that although stress test results may be negative, ongoing symptoms may warrant additional cardiac evaluation and/or referral to other disciplines.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
chest pain; coronary artery disease; exercise treadmill test; nuclear exercise stress test; pharmacologic stress test; stress echocardiography; stress testing