1. ANSWER: E. Pharmacologic MPI is reserved for patients who are unable to exercise or who can exercise but fail to achieve at least 85% of the maximal age-predicted heart rate. Thus, patients with severe peripheral vascular disease and neurologic and muscular disorders have exercise limitations and patients who cannot increase their heart rates sufficiently due to chronotropic incompetence are candidates for pharmacologic stress. Patients with LBBB or electronically paced rhythms may develop a septal perfusion abnormality in the absence of septal branch or LAD disease due to decreased septal blood flow at rapid heart rates. With pharmacologic stress, the heart rate does not increase and specificity is improved. Dobutamine stress is not appropriate as it increases heart rate. In such patients, if there is an associated anterior or apical defect in addition to the septal abnormality, this is usually associated with LAD artery disease.

Patients with permanent pacing can also develop perfusion defects in the septum, inferior wall, and apex in the absence of disease and the mechanism also is related to asynchronous contraction of the myocardium.

Adenosine or dipyridamole and recently regadenoson are the pharmacologic agents of choice for patients with an LBBB or are ventricularly paced.

Skalidis EI, Kochiadakis GE, Koukouraki SI, et al. Phasic coronary flow pattern and flow reserve in patients with left bundle-branch block and normal coronary arteries. J Am Coll Cardiol. 1999;33:1338-1346.

2. ANSWER: A. Adenosine is a nonselective agonist that causes coronary vasodilation when it activates the A2A receptor. The other receptors (A1, A2B, and A3) when activated produce most of the side effects that include chest pain, bronchiolar constriction, mast cell degranulation (flushing), and negative chronotropic, inotropic, and dromotropic effects.

Pentoxifylline, a xanthine derivative used for intermittent claudication, can be continued prior to adenosine. Compounds such as caffeine and ami-nophylline bind to adenosine receptors without stimulating them but prevent the vasodilation induced by adenosine, regadenoson, or dipyridamole, which lowers sensitivity for detection of CAD. Caffeine should be held 12 to 24 hours prior to the test and aminophylline-containing compounds for 24 to 48 hours depending on the formulation. If patients are taking dipyridamole, it should be held for 24 to 48 hours. If dipyridamole has been taken orally and intravenous dipyridamole is used as a stressor, the patient already has some degree of vasodilation and the resting study will have a high baseline blood flow and the flow reserve during stress is decreased. If dipyridamole has been taken and adenosine or regadenoson are used for pharmacologic stress, their half-lives are markedly prolonged due to inhibition by dipyridamole of the bidirectional adenosine transport mechanism that is responsible for the short half-lives of these compounds.

Patients with severe obstructive lung disease with active wheezing should not undergo adenosine or dipyridamole stress testing due to the activation of the A2B/A3 receptors that produce bronchial constriction. However, American Society of Nuclear Cardiology (ASNC) recommends patients with adequately controlled obstructive lung disease can undergo an adenosine stress test and can have pretreatment with one to two puffs of albuterol or a comparable inhaler.

AV block occurs in ˜7.6% of patients receiving adenosine but is very rare with dipyridamole. However, the incidence of second-degree AV block is only 4% and that of complete heart block is <1%. The presence of second- or third-degree AV block or sick sinus syndrome without a pacemaker is a contraindication to adenosine, regadenoson, or dipyridamole stress due to the activation of A1 receptors that are located in the SA, AV, atrial, and ventricular myocytes producing negative chronotropic, inotropic, and dromotropic effects.

Boger LA, Volver LL, Herstein GK, et al. Best patient preparation before and during radionuclide myocardial perfusion imaging studies. J Nucl Cardiol. 2006;13:98-110.

Henzlova MJ, Cerqueira MD, Mahmarian JJ, et al. Stress protocols and tracers. J Nucl Cardiol. 2006;13:e80-e90.

O’Keefe JH Jr, Bateman TM, Barnhart CS. Adenosine thallium-201 is superior to exercise thallium-201 for selecting coronary artery disease in patients with left bundle-branch block. J Am Coll Cardiol. 1999;21:1332-1338.

3. ANSWER: E. E is a class I indication with level of evidence B. In patients unable to exercise who are not scheduled to undergo cardiac catheterization, dipyridamole, adenosine, or regadenoson MPI prior to or early after discharge to look for inducible ischemia is indicated since the results can further risk stratify the patient and help the clinician select the most appropriate treatment strategy.

All of the other patients have had coronary angiography and treatment and are stable, are very unstable and need coronary angiography, or are scheduled for coronary angiography. In such patients, SPECT MPI will not provide further diagnostic or management information. In patients with coronary angiography who had intermediate lesions that need to be assessed, testing once patients have recovered may be useful.

Antman EM. 2004 update: a report of the ACC/AHA Task Force on Practice Guidelines. (Committee on Management of Acute Myocardial Infarction). Available at http://www.acc.org

4. ANSWER: D. Small left ventricular chamber size adversely affects image quality and diagnostic accuracy especially if using thallium-201 SPECT MPI. Women have smaller hearts than men, which diminishes accuracy.

Breast attenuation can produce anterior wall defects that may mimic an LAD distribution infarction. Technetium-99 agents with ECG gating have less attenuation and give better gated images than thallium-201, which improves accuracy by improving specificity.

Specificity for diagnosing CAD is reduced to 65% to 70% due to breast tissue artifact but can be improved to 85% to 90% range when clinicians integrate the rotating projection images, wall motion, and attenuation correction.

The AHA recommends MPI in men or women if they have intermediate to high pretest likelihood for CAD where the test is likely to reclassify patients into to a high- or low-risk category.

PET has higher diagnostic accuracy than SPECT in women with improved accuracy by more successfully addressing such problems as breast attenuation, obesity, and small heart size.

Mieres JH, Shaw LJ, Arai A, et al.; Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: Consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation. 2005;111(5):682-696.

Sampson UK, Dorbala S, Limaye A, et al. Diagnostic accuracy of rubidium-82 myocardial perfusion imaging with hybrid positron emission tomography/computed tomography in the detection of coronary artery disease. J Am Coll Cardiol. 2007;49(10):1052-1058.

5. ANSWER: D. The presence of renal dysfunction predisposes to accelerated atherogenesis and increased cardiovascular event risk. Al-Mallah MH demonstrated that mortality almost doubles in patients with moderate or severe renal impairment (GFR < 60 mL/min/1.73 m²) in the presence of an abnormal stress SPECT MPI.

Dahan evaluated the utility of SPECT imaging in hemodialysis patients and found that the negative predictive value is 91% after 2.87 years of follow-up for major cardiovascular events and that sensitivity and specificity for detection of disease are similar to a population not on dialysis.

Although a small study, Dussol evaluated 97 patients prior to renal trans plantation and found that 10% had inducible ischemia on SPECT and that these patients had increased adverse event rates.

There is a significant interaction between ischemia on SPECT MPI and renal function. The more severe the renal dysfunction, the higher the probability of having an abnormal SPECT study, and the more severe the ischemia. There are many postulated mechanisms for this relationship that are beyond the scope of this review.

Al-Mallah MH, Hachamovitch R, Dorbala S, et al. Incremental prognostic value of myocardial perfusion imaging in patients referred to stress single-photon emission computed tomography with renal dysfunction. Circ Cardiovasc Imaging. 2009;2:429-436.

Dahan M, Viron BM, Faraggi M, et al. Diagnostic accuracy and prognostic value of combined dipyridamole-exercise thallium imaging in hemodialysis patients. Kidney Int. 1998;54:255-262.

Dussol B, Bonnet JL, Sampol J, et al. Prognostic value of inducible myocardial ischemia in predicting cardiovascular events after renal transplantation. Kidney Int. 2004;66:1633-1639.

6. ANSWER: A. The use of nitrates in conjunction with rest technetium-99m sestamibi SPECT MPI has been shown to improve detection of viable myocardium, similar to the results observed with thallium-201. Compared with resting technetium-99m sestamibi studies alone, nitrate-enhanced SPECT has a greater ability to predict improvement of regional function after revascularization and to provide important prognostic information. The demonstration of “defect reversibility” on nitrate-enhanced compared to resting images may have better accuracy than either technique alone.

7. ANSWER: B. Although evaluated in a smaller number of studies than SPECT, stress echocardiography, and the exercise ECG, cardiac PET has the highest sensitivity and specificity of currently available noninvasive modalities. SPECT has a reported higher sensitivity and lower specificity in comparison to stress echocardiography. In comparison to the stress ECG, SPECT has both a higher sensitivity and specificity. In all the published studies for any given modality, the population under study has a major influence on the accuracy of the studies. Imaging studies performed in a very low-risk population are likely to have more false positives as the prevalence of disease will be lower, and this results in lower test specificity. Similarly, when the prevalence of CAD is very high, negative studies have a higher probability of being false negatives resulting in a lower sensitivity. It is also very important to define the gold standard to determine whether an imaging study is positive or negative. Studies using patients clinically referred for coronary angiography before or after an imaging study suffer from posttest referral bias. That is, patients with a normal imaging study are not as likely to be referred for coronary angiography. Published studies estimate a referral bias of ˜3%. This posttest referral bias may result in a lower specificity and may increase the reported sensitivity.

Fleischmann KE, Hunink MG, Kuntz KM, et al. Exercise echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance. JAMA. 1998;280:913.

Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med. 1999;130:719.

Marwick T, D’Hondt AM, Baudhuin T, et al. Optimal use of dobutamine stress for the detection and evaluation of coronary artery disease: combination with echocardiography or scintigraphy, or both? J Am Coll Cardiol. 1993;22:159.

8. ANSWER: B. In a female patient with a low pretest probability for CAD who has a normal baseline ECG and is capable of exercising, SPECT MPI is not indicated and a stress ECG is the best initial test. A patient with an intermediate probability of CAD and LVH on the baseline ECG is the best candidate for exercise stress SPECT. The ECG alone would not be diagnostic and imaging is required. In patients with an intermediate probability of CAD who are unable to exercise, pharmacologic stress SPECT is the best test and not exercise. In a patient with known CAD and typical symptoms, the probability of graft stenosis or progression of native CAD is sufficiently high that coronary angiography may be the best initial test.

9. ANSWER: A. Failure to achieve 85% of the maximal age-predicted heart rated during exercise stress may not cause enough of an increase in coronary blood flow to create sufficient flow heterogeneity between areas of the myocardium supplied by an artery with a critical stenosis and those with nonstenosed arteries when the radiotracer is injected. Although the presence of clinical endpoints such as typical anginal symptoms or profound ECG changes of ischemia are reasons to inject the radiotracer at a submaximal heart rate, tracer administration without these endpoints or the target heart rate will result in the absence or a smaller degree of inducible ischemia and a lower sensitivity.

Heller GV, Ahmed I, Tilikemeier PL, et al. Influence of exercise intensity on the presence, distribution, size of thallium-201 defects. Am Heart J. 1992;123:909.

Iskandrian AS, Heo J, Kong B, et al. Effect of exercise level on the ability of thallium-201 tomographic imaging in detecting coronary artery disease: analysis of 461 patients. J Am Coll Cardiol. 1989;14:1477.

10. ANSWER: C. All but choice C is advantage of a technetium-99 single-isotope imaging strategy. Dual-isotope studies can be performed in a much shorter time period as there is no waiting for liver clearance as is required with the technetium-99 tracers and the studies can be completed in a much shorter time interval. The radiation exposure of dual-isotope imaging is 25 to 30 mSv, while single-isotope rest/stress technetium-99 imaging is ˜8 to 15 mSv. Attenuation correction to determine attenuation artifact has been validated for technetium-based imaging agents but not thallium-201.

Thompson RC, Cullom SJ. Issues regarding radiation dosage of cardiac nuclear and radiography procedures. J Nucl Cardiol. 2006;13:19.

11. ANSWER: B. Although chronotropic incompetence has been shown to predict future cardiac events, it is not a variable that was included in the original Duke Treadmill Score.

Mark DB, Hlatky MA, Harrell FE Jr, et al. Exercise treadmill score for predicting prognosis in coronary artery disease. Ann Intern Med. 1987;106(6):793-800.

Mark DB, Shaw L, Harrell FE Jr, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med. 1991;325(12):849-853.

12. ANSWER: C. Uncompensated CHF unstable angina and critical valvular heart disease are contraindications for exercise stress testing.

Stable post-myocardial infarction patients can be evaluated with pharmacologic stress to assess prognosis and residual ischemia and need for coronary angiography.

13. ANSWER: B. SPECT improves specificity without compromising sensitivity in the detection of CAD in women compared to exercise ECG stress testing alone.

Mieres JH, Shaw LJ, Hendel RC, et al. A report of the American Society of Nuclear Cardiology Task Force on Women and Heart Disease (writing group on perfusion imaging in women). J Nucl Cardiol. 2003;10:95.

14. ANSWER: B. SPECT MPI without attenuation correction is adversely influenced by the presence of different tissue densities and the distance between the heart and the gamma camera. Camera distance from the patient, whether due to obesity or poor positioning at the time of acquisition, results in lower counts and poor quality studies. Breast size, density and position, and diaphragmatic position and thickness all cause attenuation resulting in low counts in the covered portions of the myocardium and the appearance of less tracer uptake in the presence of normal coronary blood supply. LVH may improve count statistics, which results in better-quality images with the risk of hiding small areas of ischemia.

15. ANSWER: C. Abdominal protuberance due to obesity or ascites can cause elevation of the diaphragm and greater inferior wall attenuation and the need to position the gamma camera head further from the patient, which will lower total counts and give poor image quality. Chest wall obesity also requires positioning the gamma camera head further from the patient, and there is greater tissue density to cause attenuation. Although morbidly obese male patients may have substantial gynecomastia, the breast tissue is unlikely to shift in position between the rest and stress studies as is commonly seen in females who have pendulous breasts. An elevated diaphragm for whatever reason is likely to cause diaphragmatic attenuation.

16. ANSWER: D. Breast attenuation artifacts are seen in 40% of myocardial perfusion images in women. These artifacts are often present in the anterior wall leading to a lower specificity to correctly diagnose CAD in the LAD territory.

17. ANSWER: D. The use of technetium-99-radiolabeled perfusion agents results in less attenuation and scatter and gives higher-quality images than thallium-201. Review of the rotating projection images in cine format allows identification of the position of the diaphragm and breasts and estimation of the movement of the heart in the vertical and horizontal planes. Using gender-matched normal files for quantitative analysis helps to eliminate attenuation artifact. The type of stress does not influence attenuation while the higher background usually seen with pharmacologic stress results in poor image quality.

18. ANSWER: B. Normal databases are usually matched for type of protocol, form of stress, and the type of agent. Of the variables listed, gender-matched normal files improve specificity most by accounting for differences in the amount of breast attenuation. Age, weight, and risk factors are useful to give a pretest probability of disease but do not help with artifact recognition.

19. ANSWER: A. Prone imaging (patient lies on abdomen) provides greater separation between the heart and the diaphragm, so there is less inferior wall attenuation in comparison to a supine image (patient lays on back). Patients are usually imaged both prone and supine and a comparison is made. Most available normal files are for supine imaging. Patient motion, breast attenuation, and residual liver activity can be seen on both the prone and supine images.

20. ANSWER: C. Traditional gated SPECT has a low spatial and temporal resolution compared to echocardiographic methods. Spatial resolution varies from 14 to 16 mm and the temporal resolution is restricted to 8 or at most 16 time frames for the RR interval. Greater temporal resolution is limited by the resulting low counts in each time interval. ECG-gated SPECT is generated from all the cardiac cycles throughout the acquisition process. The gated images can help differentiate perfusion defects due to scar, which do not move or thicken, and attenuation defects that move and thicken. The ejection fraction is not a measure of diastolic function but rather systolic function. Diastolic function is not assessed by the EF but by looking at the diastolic filling curves. Eight frames do not provide enough temporal resolution to accurately measure the rapid ventricular filling period, but 16 frames have been used for diastolic analysis.

21. ANSWER: C. Both technetium-99 sestamibi and tetrofosmin are cleared from the liver in a time-dependent manner. Having the patient drink large amounts of water or small amounts of a carbonated liquid, which will release gas, will not enhance liver clearance and the recommended imaging time after pharmacologic stress or rest is 30 to 60 minutes. Imaging immediately after pharmacologic stress will result in significant liver retention. Delaying image acquisition and adding exercise to the stress tests can lead to better clearance and therefore lower liver and gastrointestinal counts.

22. ANSWER: D. All of the choices are appropriate indications for using pharmacologic stress. Inability to exercise or to achieve target heart rate is a clear reason to perform pharmacologic stress. In the presence of LBBB or an electronic ventricular-paced rhythm, septal perfusion defects maybe observed with dynamic exercise stress that lower specificity. These false positives are decreased when using pharmacologic stress.

23. ANSWER: D. Dobutamine is a stress inotropic agent that can be used for pharmacologic stress testing in patients with active airway disease or in patients being treated with theophylline. In such patients, dipyridamole, adenosine, or regadenoson may cause further airway decompensation by stimulation of adenosine A2B or A3 receptors that mediate bronchospasm. In patients taking theophylline, which blocks the adenosine receptors and is used to treat side effects induced by the vasodilators, these agents may not sufficiently augment coronary blood flow to provide a diagnostic study. Dobutamine is less useful when patients are being treated with beta-blockers as they are less likely to achieve 85% of the maximal age-predicted heart rate. Dobutamine is not preferred in patients in atrial fibrillation, and it does not have greater sensitivity over the vasodilators.

24. ANSWER: A. All of these agents act as direct or indirect vasodilators of the resistance arterioles varying from 2.4 to 4.5 times above the baseline blood depending on the agent. Regadenoson gives a more physiologic increase in blood flow relative to adenosine and dipyridamole, which give a greater response. In severely obstructed vessels, the arterioles are maximally dilated at baseline, and therefore, no significant vasodilation can be induced with these agents.

Chambers CE, Brown KA. Dipyridamole-induced ST segment depression during thallium-201 imaging in patients with coronary artery disease: angiographic and hemodynamic determinants. J Am Coll Cardiol. 1988;12:37.

Nishimura S, Kimball KT, Mahmarian JJ, et al. Angiographic and hemodynamic determinants of myocardial ischemia during adenosine thallium-201 scintigraphy in coronary artery disease. Circulation. 1993;87:1211.

25. ANSWER: B. Activation of A1 receptors causes AV conduction delay or AV nodal block. Activation of A2B and A3 receptors can mediate bronchospasm by facilitating mast cell degranulation. Activation of adenosine A2A receptors causes coronary vasodilation. Adenosine and dipyridamole cause direct nonselective stimulator of all these receptors.

Shryock JC, Belardinelli L. Adenosine and adenosine receptors in the cardiovascular system: biochemistry, physiology, and pharmacology. Am J Cardiol. 1997;79:2.

26. ANSWER: D. The cardiovascular effects of adenosine include:

Shryock JC, Belardinelli L. Adenosine and adenosine receptors in the cardiovascular system: biochemistry, physiology, and pharmacology. Am J Cardiol. 1997;79:2.

27. ANSWER: C. Dipyridamole is primarily metabolized in the liver and should be used cautiously in patients with hepatic dysfunction. The biologic half-life of dipyridamole is 30 to 45 minutes. Adenosine but not dipyridamole is rapidly taken up by red blood cells and endothelial cells, and this explains the short biologic half-life of adenosine. The longer half-life makes it a good agent for PET imaging as it does not need to be given as a continuous infusion over an extended time period.