When and in Whom Should Stress Myocardial Perfusion Imaging be Performed

General description of procedure, equipment, technique

Stress myocardial perfusion imaging is a nuclear cardiology procedure that is widely used to assess patients with known or suspected coronary artery disease. This technique measures myocardial perfusion during stress, and often at rest, after the injection of a small amount of a radiopharmaceutical that is extracted by myocardial cells in proportion to myocardial blood flow.

After the injection of the radiopharmaceutical, images are obtained using a nuclear camera using a technique called single photon emission computed tomography (SPECT) or positron emission tomography (PET). The acquired images then are assessed to determine whether myocardial perfusion during stress is normal or abnormal, and if needed, whether there is any change in perfusion from stress to rest.

Analysis of these images provides important prognostic and diagnostic information, and accurately determines the extent and location of myocardial ischemia and/or infarction. The study also provides data on left ventricular size and function, including left ventricular ejection fraction.

Stress modalities used

The preferred stress modality is exercise. Patients undergo exercise stress using standard treadmill protocols (e.g., Bruce protocol), which includes monitoring the electrocardiogram (ECG), hemodynamics, and patient’s symptoms. The goal is to perform a symptom limited test; that is, to attempt to reproduce the symptoms that were responsible for the ordering of the test.

If the test is being performed on patients without known CAD, for purposes of diagnosis of CAD, the best sensitivity is obtained if the patient reaches at least 85% of their age-predicted maximum heart rate. The radiopharmaceutical is injected at peak stress, and the patient is imaged shortly thereafter.

If a patient cannot exercise due to limitations such as musculoskeletal disorders or noncardiac illness, or if the patient has a left bundle branch block on ECG, then pharmacologic stress can be used instead of exercise. The preferred pharmacologic stressors for myocardial perfusion imaging are the coronary vasodilators dipyridamole, adenosine, and regadenoson. Because of the mechanism of action of these vasodilators, in some cases, particularly patients with active bronchospasm, dobutamine may be used instead of the vasodilators.

Indications and patient selection

The primary indications for stress myocardial perfusion imaging are: (1) for diagnostic purposes in patients with suspected CAD; and (2) for prognostic purposes in patients with known CAD or symptoms suggestive of CAD. The major strength of the technique is its ability to provide powerful prognostic information in a wide range of patient populations, including patients with known CAD, at high risk for CAD, post-myocardial infarction, diabetes, advanced age, obesity, and women.

The most appropriate patients for whom this test should be considered include: (1) patients at intermediate-to-high risk for CAD who are having symptoms suggestive of CAD; (2) patients with known CAD who have new or recurring symptoms that may be attributable to myocardial ischemia; (3) patients with prior revascularization who have recurrent symptoms; and (4) patients who have had recent myocardial infarction who did not undergo an early cardiac catheterization and reperfusion treatment strategy.

Selected lower risk patients may be candidates for this study as well, particularly if they cannot exercise or if the ECG is not interpretable (left bundle branch block, ventricular pacing, severe baseline ST segment abnormalities), since pharmacologic stress is required in these cases, and necessarily must be performed in conjunction with cardiac imaging. This study may be indicated for the preoperative risk stratification prior to high-risk noncardiac surgery, if the results of the study will impact on the perioperative management of the patient.

The most detailed criteria available to select patients for this procedure are the “Appropriate Use Criteria for Cardiac Radionuclide Imaging” that is published by the American College of Cardiology and other cardiology or imaging societies.

Contraindications

Major contraindications to stress myocardial perfusion imaging include: acute coronary syndromes prior to medical stabilization, critical aortic stenosis, known or suspected high-grade left main coronary artery stenosis, uncontrolled arrhythmias, decompensated congestive heart failure, acute aortic dissection, acute myocarditis, or any severe noncardiac medical illness that may preclude stress.

Details of how the procedure is performed

Myocardial perfusion imaging is comprised of two parts: the stress test and the imaging component. Stress testing is performed with exercise or pharmacologic stress (dipyridamole, adenosine, regadenoson, or dobutamine), with continuous electrocardiographic monitoring.

Exercise is the stressor of choice, unless the patient is unable to perform a symptom-limited test. Exercise is performed in a 5 to 60 minutes after completion of stress.

Depending on the protocol used, resting myocardial perfusion images often are obtained as well; these may be obtained before or after stress imaging, or on a separate day. In an attempt to reduce radiation exposure, if a patient has a normal stress test and normal imaging, the interpreting physician may decide that the resting images may not be required.

Patient preparation:

NPO for 4 hours before the test.
No caffeine products for a minimum of 12, and preferably for 24 hours, prior to the test.
Comfortable clothing.
Depending on the indication for the test and patient’s history, certain medications may be stopped prior to the test. For patients without a history of known CAD, it is generally recommended to titrate off beta-blockers for 24 to 48 hours prior to the test. In case pharmacologic testing is required, medications containing caffeine, phosphodiesterase inhibitors, or adenosine receptor agonists or antagonists are usually held; these include aminophylline, theophylline, analgesics containing caffeine, and medications containing dipyridamole.
Women of childbearing potential usually require a pregnancy test prior to the exam.

Upon completion of the test, no specific postprocedure care is required. The patient should resume usual medications.

Interpretation of results

Depending on the setting in which stress testing is performed, the stress test and the myocardial perfusion imaging may be interpreted separately, although it is essential that information from both parts of the study are integrated into the evaluation and management of the patient. Data obtained from the stress test that provide diagnostic and prognostic information include the duration of exercise, the maximum level of exercise (usually reported in METs), the heart rate and blood pressure response, the development of symptoms, and electrocardiographic changes in response to stress, especially ST-segment depressions and elevations.

Additional prognostic information can be provided by calculating the Duke treadmill score, which is based on the duration of exercise, maximum ST segment changes, and presence of anginal symptoms. High-risk findings for exercise stress testing include the development of ST elevations during exercise, the development of ischemic ECG changes or angina at low levels of exercise, a decrease in blood pressure >10 mm Hg during exercise, persistent ischemic ECG changes or angina during the postexercise recovery phase, the development of pulmonary edema, or a Duke treadmill score of -11 or lower.

Interpretation of the perfusion images is based on the identification of regions of reduced radiotracer uptake in the myocardium. These defects are classified as “reversible” if they are present on the stress images, but not the rest images, or “fixed” if they are present on both the stress and rest images.

Reversible defects are consistent with the presence of ischemia, while fixed defects are consistent with the presence of scar tissue. “Partially reversible” defects represent the presence of both scar tissue and viable, ischemic tissue in an area of the heart.

The interpretation of myocardial perfusion images is aided by the use of a variety of commercially available software programs that quantify the severity and extent of perfusion defects. Quantification of the size and severity of perfusion defects provides important prognostic information as described below.

If ECG-gating of the perfusion study is performed, it is possible to obtain information concerning the ejection fraction and segmental wall motion. High-risk findings from the myocardial perfusion imaging include the presence of large perfusion defects and/or perfusion defects involving multiple vascular territories, an increased uptake of radiotracer in the lung compared to the heart (lung/heart ratio), transient ischemic dilation (TID) of the left ventricle, stress-only visualization of the right ventricle, and stress-induced left ventricular dysfunction. These high-risk findings are generally associated with the presence of severe, multivessel, or left main disease.

Performance characteristics of the procedure (applies only to diagnostic procedures)

In a recent meta-analysis of 114 SPECT studies and 14 PET studies, the sensitivity for detecting coronary artery disease was 88% for SPECT and 84% for PET. The specificity was 61% and 81% for SPECT and PET, respectively.

The greater specificity of PET comes from its greater ability to avoid artifacts because of the higher energy of the gamma photons imaged by PET cameras, the use of coincidence detection, and attenuation correction. The negative predictive value for myocardial perfusion imaging approaches 99%. The sensitivity and specificity of myocardial perfusion imaging is similar for the various stress protocols (i.e., exercise, adenosine, dipyridamole, regadenoson, dobutamine).

As noted above, myocardial perfusion imaging provides not only diagnostic information (a patient does/does not have coronary artery disease), but provides important prognostic information based on the severity and extent of perfusion defects and the presence of high-risk findings. In patients with normal studies, the overall annual rate of myocardial infarction or cardiac death is <1%.

Even in patients with small perfusion defects, the risk of cardiac events is approximately 1%. It is important to recognize, however, that patients with a history of coronary artery disease or diabetes are still at higher risk, even if they have a normal stress test.

With increasing size and severity of perfusion defects, the risk of myocardial infarction or cardiac death increases. Patients with moderately abnormal myocardial perfusion studies can have an annual cardiac event rate of 2% to 4%, and those with severely abnormal scans have annual cardiac event rates over 5%. As a result, myocardial perfusion imaging can be extremely helpful in risk stratifying an individual and determining if a strategy of medical management vs. revascularization is better for the patient.

Alternative and/or additional procedures to consider

In addition to stress testing with myocardial perfusion imaging, several other noninvasive and invasive techniques can be used to detect coronary artery disease. The most common other technique is stress echocardiography, with either exercise or dobutamine used as the stressor.

The benefits of stress echocardiography over myocardial perfusion imaging are that the use of ionizing radiation is avoided and echocardiographic equipment is widely available; however, it is limited by a decreased sensitivity in patients with baseline wall motion abnormalities and obtaining stress echocardiograms in patients with inadequate imaging windows can be challenging.

CT angiography has also been used for noninvasive assessment of coronary stenoses, but also relies on ionizing radiation. In addition, it requires the use of iodinated contrast and therefore cannot be used in patients with renal disease or contrast allergies. The diagnostic characteristics of each of these noninvasive imaging modalities are similar. Finally, invasive coronary angiography can be used to evaluate coronary artery disease, but its use is generally guided by the results of noninvasive imaging studies.

Complications and their management

The risks of stress myocardial perfusion imaging can be considered in two parts: the risk of stress testing and the risk of nuclear imaging.

Both exercise and pharmacologic stress are safe procedures, with very low rates of serious complications. For exercise stress, the overall risk of mortality is less than 0.01%; and of serious complications, less than 0.05%.

Major complications include myocardial infarction and sustained arrhythmias. Absolute risk of mortality and morbidity may be higher, but not necessarily prohibitive, in patients with recent acute coronary syndrome, cardiomyopathies, and symptomatic valvular disease. For pharmacologic stress, the overall risk of mortality or serious morbidity similarly is very low (less than 0.05%).

Additional side effects with pharmacologic stress, which are reversible, include: hypotension, tachycardia, headache, nausea or vomiting, dyspnea (and, with certain agents, bronchospasm), atrioventricular block, and flushing. Complications or prolonged side effects that are seen with the vasodilator stress agents are usually easily reversed with an intravenous injection of aminophylline.

The main risk associated with the nuclear imaging component of this test is that of low level radiation exposure (3 to 25 mSv depending on the type of radiotracer that is used, whether both stress and rest imaging are required, and patient-dependent factors). The risk of exposure to low levels of radiation from medical procedures is unclear, and is estimated to be very low, such that the benefits of performing the study in the appropriate patient should far exceed any very small, long-term risk from radiation exposure.

What’s the evidence?

Cerqueira, MD, Allman, KC, Ficaro, EP. “Recommendations for reducing radiation exposure in myocardial perfusion imaging”. J Nucl Cardiol. vol. 17. 2010. pp. 709-18. (This paper reviews current recommendations for performing a nuclear stress myocardial perfusion study using the best combination of imaging parameters and radiopharmaceutical dose so that the highest quality study is obtained with the lowest possible radiation exposure to the patient.)

Hachamovitch, R, Hayes, S, Friedman, JD. “Determinants of risk and its temporal variation in patients with normal stress myocardial perfusion scans: what is the warranty period of a normal scan?”. J Am Coll Cardiol. vol. 41. 2003. pp. 1329-40. (This paper highlights an important aspect of stress myocardial perfusion imaging (i.e., that a normal study, even in the presence of known heart disease, is associated with a favorable prognosis for cardiac events for several years ahead).

Hendel, RC, Berman, DS, Di Carli, MF. “ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging: A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine”. J Am Coll Cardiol. vol. 53. 2009. pp. 2201-29. (This paper describes the appropriate use criteria for stress myocardial perfusion imaging, which can be used to guide clinicians when assessing whether such a study is appropriate for a particular clinical scenario.)

Henzlova, MJ, Cerqueira, MD, Mahmarian, JJ, Yao, SS. “Quality Assurance Committee of the American Society of Nuclear C. Stress protocols and tracers”. J Nucl Cardiol. vol. 13. 2006. pp. e80-90. (This paper describes specific aspects and methods of stress testing and nuclear imaging protocols relevant to nuclear cardiology.)

Jaarsma, C, Leiner, T, Bekkers, SC. “Diagnostic performance of noninvasive myocardial perfusion imaging using single-photon emission computed tomography, cardiac magnetic resonance, and positron emission tomography imaging for the detection of obstructive coronary artery disease: a meta-analysis”. J Am Coll Cardiol. vol. 59. 2012. pp. 1719-28. (This paper summarizes the data for using the major advanced cardiac imaging modalities for the detection of coronary artery disease.)

Mark, DB, Shaw, L, Harrell, FE. “Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease”. N Engl J Med. vol. 325. 1991. pp. 849-53. (This paper describes a method by which stress ECG testing [with no cardiac imaging] can be used to assess prognoses in patients with suspected coronary artery disease.)

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