General description of procedure, equipment, technique
Stress echocardiogram, when performed to diagnose coronary artery disease (CAD), aims at documenting inducible left ventricular wall motion abnormalities. It should be ordered only if the test results are expected to significantly affect patient management. To decrease the number of false-positive test results, stress echocardiogram should not be performed in patients with low probability of coronary artery disease, such as young patients without significant risk factors for coronary artery disease with non-anginal chest pain.
Before the test is started, the patient should be interviewed and examined for any signs of acute or chronic illnesses, which may preclude stress testing. Vital signs and examination should be normal, without heart failure or uncontrolled arrhythmia. Stress testing should not be performed in patients with acute illnesses, such as evolving myocardial infarction or unstable angina, pneumonia, pneumothorax, gastro-intestinal bleeding, etc. Chest pain with normal baseline LV systolic function and normal ECG does not necessarily preclude stress testing. However, the causes of the chest pain should be sought and targeted physical examination is required.
The patient should present in fasting state. Ability to walk on the treadmill should be assessed. In non-ambulatory patients and those unable to perform the desired level of upright exercise, treadmill testing should be changed to supine bicycle with or without dobutamine infusion. Alternatively, dobutamine infusion may be used alone.
Following the patient interview, physical examination, and consent, a baseline 12 lead electrocardiogram and 2 dimensional echocardiographic images of the left ventricle are acquired. Echocardiographic images include parasternal long axis, parasternal short axis, apical 4 chamber and apical 2 chamber views of the left ventricle. The images are QRS gated and displayed in a quad format in a continuous cine loop. If baseline images have wall motion abnormalities, these may be attributed to coronary artery disease, and previous myocardial infarction should be considered.
During the exercise test, the patient walks on the treadmill, pedals the bicycle, and/or receives dobutamine infusion to increase the heart rate to the target. The target heart rate is equal to 85% of (220 – patient age in years).
The proper exercise equipment for a stress echocardiogram includes treadmill or supine bicycle with software allowing for the administration of a graded level of resistance, run by a trained technician. When dobutamine infusion is used instead of walking on the treadmill or pedaling the bicycle, a trained nurse administers escalating doses of dobutamine, using a commercially available infusion pump. During the test, continuous ECG monitoring is performed and blood pressure is periodically recorded.
Upon reaching the target heart rate or test termination for any reason, the patient is transferred to the imaging position and 2 dimensional echocardiographic images are acquired. Echocardiographic images are obtained with commercially available sonographic equipment by experienced sonographers capable of acquiring cardiac images within 1 minute, preferably during the initial 30 seconds after the completion of the exercise. While the patient remains in the supine position, intermittent blood pressure is taken, and continuous ECG monitoring is performed. The test is completed when the heart rate and blood pressure return to baseline values.
Stress test interpretation should be performed by an experienced echocardiographer.
Immediate post-exercise (peak heart rate) images are compared to the baseline images to identify new left ventricular (LV) wall motion abnormalities. If new LV wall motion abnormalities are present, the test result is considered to be consistent with ischemia. If no wall motion abnormalities are present and target heart rate has been achieved, the test result is considered negative for ischemia. If no wall motion abnormalities are present, but the target heart rate has not been achieved, the test is considered be non-diagnostic for the presence of ischemia. The complete ECG recording is reviewed for signs of ischemia and/or arrhythmia, and reported together with the echocardiographic findings.
Indications and patient selection
Before the test is ordered, the pre-test probability of coronary artery disease needs to be assessed. Low pre-test probability (<10%) increases the false negative test result rate, high pre-test probability (90%) makes false-negative result more likely.
Pre-test probability varies by patient’s gender, age, and chest pain character. Additional criteria include presence of diabetes, smoking, and/or hyperlipidemia. To simplify the pre-test probability assessment, patients with typical angina, regardless of age and gender, are considered to have high pre-test probability. Patients with non-anginal pain younger than 35 years old are considered to have low pre-test probability. The rest of the patients, depending on co-morbidities, can have intermediate or high pre-test probability. Diabetes and/or peripheral vascular disease are considered coronary artery disease equivalents. Risk of coronary artery disease event and pre-test probability of coronary artery disease can be stratified using nomograms and tables correlating pain quality, age, and gender.
Stress echocardiography is considered appropriate in the evaluation of those with chest pain or anginal equivalents when the resting ECG is uninterpretable, when there is intermediate or high pre-test probability of coronary artery disease, regardless of the ability to exercise, with ventricular tachycardia, with new onset heart failure and normal baseline LV systolic function, and before intermediate or higher risk surgery in patients with low exercise capacity with at least intermediate pre-test probability of coronary artery disease.
Stress echocardiography is considered inappropriate in patients with the following: low pre-test probability of coronary artery disease, ECG without significant ST changes precluding interpretation, chest pain and high pre-test probability of coronary artery disease, acute ST elevation myocardial infarction, valvular disease requiring surgical treatment, and new onset atrial fibrillation and low pre-test probability of coronary artery disease.
Stress testing should not be performed in patients with acute illnesses, i.e., evolving myocardial infarction or unstable angina, critical aortic valve stenosis, severe anemia, pneumonia, pneumothorax, uncontrolled asthma or other significant breathing difficulties, hypokalemia, or any acute systemic illness.
Absolute contraindications to stress testing include recent (within 48 hours) myocardial infarction, unstable angina not stabilized on medical therapy, uncontrolled arrhythmias, symptomatic severe aortic stenosis, acute pulmonary embolism or pulmonary infarction, acute myocarditis or pericarditis, and/or acute aortic dissection.
Relative contraindications include known left main coronary artery stenosis, moderate symptomatic stenotic valvular disease, hypertrophic cardiomyopathy with left ventricular outflow obstruction, electrolyte abnormalities, uncontrolled hypertension with systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg, tachy or bradyarrhythmias, and mental or physical impairment leading to the inability to exercise.
Chest pain with normal baseline LV systolic function and normal ECG should not preclude stress testing.
Details of how the procedure is performed
The patient should be instructed to fast and abstain from drinking fluid or smoking for 3 hours before the test. No unusual physical efforts should be performed within 12 hours before the test. When feasible, anti-anginal medications and phosphodiesterase inhibitors should be stopped for 24-72 hours prior to the test.
A baseline 12 lead ECG is done after vital signs have been obtained. A standard 12 lead ECG is performed and analyzed. Subsequently, ECG leads are repositioned to ensure optimal echocardiographic windows. Once the ECG leads have been re-positioned, a 12 lead ECG is obtained again. This ECG becomes the standard against which the exercise ECGs are compared to for changes.
After the 12 lead ECG, 2 dimensional echocardiographic images of the left ventricle are acquired. These images include parasternal long axis, parasternal short axis, apical 4 chamber, and apical 2 chamber views of the left ventricle. Images are QRS gated and displayed in a quad screen format in a continuous cine-loop. Once the ECG and baseline echocardiographic images are obtained, exercise and/or dobutamine infusion begins.
Most commonly, a Bruce protocol treadmill test is performed, which consists of graded exercise at progressively increasing speed with 3 minute stages. Stage 0 is at 1.7 mph and 0 incline, stage 0.5 is at 1.7 mph and 5% incline, stage 1 is at 1.7 mph and 10% incline, stage 2 is at 2.5 mph and 12% incline, stage 3 is at 3.4 mph and 14% incline, stage 4 is at 4.2 mph and 16% incline, and stage 5 is at 5 mph and 18% incline. Modified Bruce protocol may be used in patients with decreased exercise capacity, aiming to increase the length of exercise to 6-12 minutes.
In patients unable to exercise, intravenous dobutamine infusion is performed. Dobutamine infusion starts at 5 mcg/kg/min, with a dose increase, if tolerated, of 5 mcg/kg/min at 3 minute intervals until a maximal dose of 40 to 50 mcg/kg/min is reached, target rate is achieved, or side effects develop. When supine bicycle exercise is used, pedaling resistance is increased in 25 Watt increments, typically with 3 minutes on each stage. Dobutamine infusion may be combined with supine bicycle exercise.
If the increase in heart rate is inadequate, atropine may be given provided there are no contraindications. Atropine is usually administered intravenously at 0.1 mg increments in 3-4 minute intervals for a total of 2 mg, until the target heart rate has been achieved or side effects develop.
Heart rate may not increase despite all of the above in pacemaker-dependent patients. Pacing rate can be increased until the target heart is achieved. Typical pacing protocol starts at 10 bpm above the baseline heart rate. After that, 2 minute stages are recommended at 85% and 100% of the predicted heart rate.
Continuous ECG monitoring is performed. Blood pressure is recorded, typically at the end of each exercise stage.
Stress testing is continued until test endpoints are achieved. Test endpoints include reaching the target heart rate or the development of significant arrhythmia or moderate angina. The test may be stopped if significant ST segment changes or complications develop.
Upon termination of the test, the patient is transferred to the imaging position. Immediate post-exercise (peak heart rate) images and 12 lead electrocardiogram are acquired. The patient remains in the supine position while intermittent blood pressure readings are taken, and continuous ECG monitoring is performed until the ECG, heart rate, and blood pressure return to baseline values.
Post-exercise images include parasternal long axis, parasternal short axis, apical 4 chamber, and apical 2 chamber views of the left ventricle. Images are QRS gated and displayed in a quad screen format in a continuous cine-loop. Post-exercise and baseline images are compared to identify new or worsening LV wall motion abnormalities.
Interpretation of results
Interpretation of the exercise stress test should include exercise capacity and clinical, hemodynamic, and electrocardiographic response. Exercise capacity of less than 5 METS is associated with poor prognosis. Exercise capacity of 13 METs or greater is associated with a good prognosis.
Clinical assessment includes documentation of anginal pain or the pain syndrome that prompted the stress test. Signs of systemic hypoperfusion, e.g., pre-syncope, pallor, etc., should be noted. Blood pressure should not decrease with exercise.
The most commonly used electrocardiographic findings consistent with ischemia are ST depressions or elevation equal or greater than 1 mm (0.1 mV) at least 60 to 80 msec after the J point and/or ventricular arrhythmia during or after the exercise.
From the echocardiographic perspective, the test is considered to be consistent with ischemia if new global LV dysfunction or LV wall motion abnormalities are present, or if pre-existing LV dysfunction worsens in post-exercise images. If no wall motion abnormalities are present and target heart rate has been achieved, the test result is considered negative for ischemia. If no wall motion abnormalities are present, but the target heart rate has not been achieved, the test is considered non-diagnostic for the presence of ischemia.
Physicians interpreting the test should have formal training in supervision and interpretation of the stress echocardiography. It is recommended that at least 100 supervised procedures should be performed and interpreted during training. For physicians without formal training, a minimum of 150 procedures during 3 years are recommended. At least 25 procedures per year are recommended for maintenance of skill.
Performance characteristics of the procedure
The average reported sensitivity of the stress echocardiogram in detecting significant coronary obstruction is 88%, and the average specificity is 83%. The diagnostic sensitivity of the exercise stress echocardiogram may range from 77% to 89%, and for dobutamine echocardiogram the range is 79% to 90%, depending on the population studied and the referral bias.
The most common cause of a non-diagnostic stress echocardiogram is low exercise capacity and/or chronotropic incompetence and failure to achieve the target heart rate, frequently due to beta-blocker therapy. Excluding non-diagnostic tests due to low peak heart rate, false-negative results are more common in patients with a single vessel or circumflex disease, concentric left ventricular remodeling, and significant aortic or mitral valve regurgitation. Poor acoustic windows may preclude adequate segmental wall motion analysis, in which case imaging with an echo-contrast agent is recommended.
False-positive results are possible with non-ischemic causes of abnormal wall motion response to exercise or pharmacological stress. Examples include severe hypertension during the test, microvascular disease, myocarditis, or idiopathic cardiomyopathy. Mitral valve annular tethering may lead to a reduction in motion of adjacent basal segments. Abnormal ventricular septal motion may be seen in patients with left bundle branch block, ventricular paced rhythms, and/or after open heart surgery. In many cases, dyssynchrony can be differentiated from ischemia by preserved segmental wall thickening.
Alternative and/or additional procedures to consider
Stress echocardiography is the most cost-effective way to diagnose significant obstructive coronary artery disease when the baseline electrocardiogram is abnormal and/or improved specificity is required. In addition, stress echocardiography provides valuable information about exercise capacity and details cardiac structures and function. Echo-contrast agents have largely eliminated poor acoustic windows as a limitation of the stress echocardiography. Nowadays, a lack of the local expertise is the main reason that alternative imaging stress testing may be considered.
Alternative imaging stress testing includes myocardial nuclear perfusion (MPI) or cardiac magnetic resonance (CMR) imaging with a vasodilator and/or exercise. The diagnostic endpoint of the MPI is perfusion reduction after stress or perfusion imbalance after vasodilatation. The diagnostic sensitivity of MPI ranges from 82 to 88% for exercise and 88 to 91% for vasodilator stress. The diagnostic specificity ranges from 70% to 88% for exercise and 75% to 90% for vasodilator stress. MPI image quality is inferior in overweight patients and in women with large breasts. Balanced hypoperfusion in triple vessel or equivalent coronary artery disease may result in an underestimation of the ischemic burden.
The diagnostic endpoint of the CMR is the wall motion abnormalities with cine CMR or perfusion abnormality after vasodilatation. In some centers, gadolinium enhancement is also used to delineate scarred myocardium. Overall, experience with CMR is limited. The diagnostic sensitivity and specificity of CMR ranges from 83% to 86% for wall motion and 81% to 91% for pharmacological stress. The cost of CMR, length of the test, and advanced expertise requirements are major limiting factors.
Additional non-stress testing for coronary artery disease includes calcium scoring and cardiac computed tomography angiography (CCTA).
Calcium score, calculated as a product of calcified plaque area by maximal plaque density, can be measured with an electron beam or regular computed tomography. Pooled reported sensitivity of non-zero calcium score for obstructive coronary artery disease on angiogram is 98% and specificity is 40%. Utility of calcium scoring is questionable in young patients, in patients with soft plaques, and when calcium plaque deposits are minimal.
With CCTA, an angiographic contrast is used to delineate coronary anatomy. While the negative predictive value of CCTA is excellent, the positive predictive value is low, ranging from 29% to 44%, when ischemia on stress testing was used as a gold standard. CCTA is not a functional test. In addition, significant coronary calcifications preclude accurate assessment of the lumen patency. Existing guidelines recommend CCTA in patients who have continued symptoms with prior normal or inconclusive stress tests and in patients unable to undergo stress testing.
Complications and their management
Complications during or after stress echocardiography are uncommon, with a reported 0.05% morbidity rate and a 0.02% mortality rate. The reported incidence of myocardial infarction and death is 1 per 2,500 tests. Additional complications during stress echocardiography are classified as either absolute, requiring immediate test termination, or relative.
Absolute indications for terminating exercise testing include a decrease in blood pressure more than 10 mmHg from baseline, despite exercise, when accompanied by other evidence of ischemia, moderate to severe angina, nervous system symptoms, such as ataxia, dizziness, or near syncope or syncope, cyanosis or pallor, sustained ventricular tachycardia, ST elevation greater or equal to 1 mm (0.1 mV) in leads without diagnostic Q waves, technical difficulties in monitoring ECG or blood pressure, and the subject’s desire to stop the test.
Relative indications for terminating stress testing include a reduction in blood pressure without evidence of ischemia, excessive ST depression greater than 2 mm (0.2 mV) or a marked cardiac electrical axis shift, arrhythmias other than sustained ventricular tachycardia, new left bundle branch block or intraventricular conduction delay, hypertensive response to exercise with systolic blood pressure greater than 250 mmHg or diastolic blood pressure greater than 115 mmHg, and new or worsening chest pain, fatigue, shortness of breath, wheezing, and/or leg pain.
Complications during dobutamine infusion include atrial and ventricular arrhythmias, angina and non-anginal chest pain, nausea, tremors, anxiety, and headache. Beta-adrenergic antagonists may be given intravenously to patients with prolonged ischemic responses and/or significantly increased heart rate or arrhythmias which persist after cessation of dobutamine infusion.
Providers performing stress echocardiography should possess the necessary cognitive and practical skills to recognize and treat possible complications.
What’s the evidence?
Fletcher, G, Froelicher, V, Hartley, L. “Exercise standards. A statement for health professionals from the American Heart Association”. Circulation.. vol. 82. 1990. pp. 2286-2322. (This is an important source of information about exercise stress testing in general. Applies to all readers who do stress testing. This is about how to do the test.)
Gibbons, R, Balady, G, Beasley, J. “ACC/AHA guidelines for exercise testing: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing)”. J Am Coll Cardiol. vol. 30. 1997. pp. 260-315. (This reference on how to perform exercise testing with imaging is useful to all practitioners who perform stress imaging. Information is complimentary to 1990 Exercise Testing Guidelines.)
Rodgers, G, Ayanian, J, Balady, G. “American College of Cardiology/American Heart Association clinical competence statement on stress testing”. J Am Coll Cardiol. vol. 36. 2000. pp. 1441-53. (This reference highlights clinical competence standards needed to perform stress testing.)
Gibbons, R, Balady, G, Bricker, J. “ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the ACC/AHA Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines)”. J Am Coll Cardiol. vol. 40. 2002. pp. 1531-40. (This is an update to the 1997 Guidelines on exercise testing with imaging. Complements, but does not replace the 1997 version.)
Douglas, P, Khandheria, B, Stainback, R. “ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/ SCMR 2008 appropriateness criteria for stress echocardiography”. J Am Coll Cardiol. vol. 51. 2008. pp. 1127-47. (Provides guidance regarding when to order stress echo.)
Douglas, P, Garcia, M, Haines, D. “ACCF/ASE/AHA/ASNC/ HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance”. J Am Coll Cardiol. vol. 57. 2011. pp. 1126-66. (Provides guidance regarding when to order the stress echo.)
Jneid, H, Anderson, J, Wright, R. “2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non–ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines”. J Am Coll Cardiol. vol. 60. 2012. pp. 645-81. (This reference provides guidance regarding the role of stress testing in patients who are stabilized after an acute coronary syndrome.)
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- General description of procedure, equipment, technique
- Indications and patient selection
- Details of how the procedure is performed
- Interpretation of results
- Performance characteristics of the procedure
- Alternative and/or additional procedures to consider
- Complications and their management
- What’s the evidence?