DIAGNOSTICS/PROCEDURES/PROTOCOLS

Question 1

When should we perform a pharmacologic stress in lieu of a treadmill test for single photon emission computed tomography myocardial perfusion imaging (SPECT MPI)

Answer 1

1. Severe symptomatic peripheral vascular disease
2. Chronotropic incompetence
3. LBBB
4. Neurologic or muscular disease

Question 2

Why do patients with chronotropic incompetence, PVD, neurologic or muscular disorders need pharm SPECT MPI?

Answer 2

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

Question 3

Why should we do pharm SPECT MPI in patients with LBBB or paced rhythms?

Answer 3

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.

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

Question 4

Pharm SPECT MPI in patients with severe COPD?

Answer 4

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.

Question 5

Pharm SPECT MPI in patients with conduction disease and no PPM?

Answer 5

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.

Question 6

Caeffine restriction prior to pharm SPECT MPI?

Answer 6

Caffeine should be held 12 to 24 hours prior to the test.

Note: Compounds such as caffeine and aminophylline bind to adenosine receptors without stimulating them but prevent the vasodilation induced by adenosine, regadenoson, or dipyridamole, which lowers sensitivity for detection of CAD.

Question 7

Aminophylline containing compounds restriction prior to SPECT MPI?

Answer 7

Aminophylline-containing compounds for 24 to 48 hours depending on the formulation

Question 8

Mechanism of action of adenosine?

Answer 8

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.

Question 9

Can pentoxiphylline be given prior to pharm SPECT MPI?

Answer 9

Pentoxifylline, a xanthine derivative used for intermittent claudication, can be continued prior to adenosine.

Question 10

When is there a role for SPECT MPI in patients with an MI (example STEMI)?

Answer 10

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.

Note: We should not do SPECT MPI if patient has undergone angiography and revascularization, scheduled for angiography or is decompensated (HF, electric or hemodynamic)

Question 11

What is the effect of heart size (LV chamber size) on SPECT MPI?

Answer 11

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.

Question 12

What is the speceficity for diagnosing CAD with SPECT MPI?

Answer 12

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.

Question 13

When should we consider SPECT MPI for diagnosing CAD?

Answer 13

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.

Question 14

How does accuracy of PET compare to SPECT MPI especially in women?

Answer 14

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.

Question 15

How does renal dysfunction relate to SPECT MPI?

Answer 15

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.

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.

Question 16

In patients with renal dysfunction and normal SPECT MPI, how are outcomes?

Answer 16

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.

Question 17

SPECT MPI in renal dysfunction patients prior to transplantation?

Answer 17

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

Question 18

Administration of nitrates prior to the resting injection technitium-99m will result in what?

Answer 18

Improves reader’s ability to detect viable myocardium in severely hypoperfused segments

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.

Question 19

What is true regarding the general sensitivity and specificity for detection of CAD of various cardiac stress testing imaging methods is true?

Answer 19

SPECT MPI is more sensitive and specific compared to exercise electrocardiogram (ECG).

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.

Question 20

What is the best candidate in terms of presenting chest pain for exercise or pharm SPECT MPI?

Answer 20

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.

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.

Question 21

Failure to achieve 85% of the maximal age-predicted heart rate during SPECT imaging may reduce the diagnostic performance by?

Answer 21

Reducing the size and severity of the perfusion defects

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.

Question 22

What is an advantage of dual-isotope SPECT MPI?

Answer 22

Improved efficiency in the nuclear cardiology laboratory

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.

Question 23

Is chronotropic incompetence a part of Duke Treadmill Score?

Answer 23

No

Question 24

What are components of Duke Treadmill score?

Answer 24

1. Typical chest pain
2. Degree of ST segment deviation
3. Exercise time

Question 25

What are contraindications to Stress SPECT MPI?

Answer 25

1. Unstable/decompensated CHF
2. Critical valvular disease
3. Unstable Angina

Question 26

Can stable post MI patients get a stress SPECT MPI?

Answer 26

Yes

Question 27

In women how is SPECT MPI better compared to stress ECG testing only?

Answer 27

SPECT improves specificity without compromising sensitivity in the detection of CAD in women compared to exercise ECG stress testing alone

Question 28

What factors can reduce quality of SPECT images or introduce artifacts?

Answer 28

1. Distance (obesity or patient position can adversly effect imaging)
2. Tissues such as breasts in women and diaphragm
   These can all reduce counts and lead to attenuation artifacts and decreased perfusion when there is normal coronary blood flow.

Question 29

How does LVH effect quality of SPECT images?

Answer 29

LVH may improve count statistics, which results in better-quality images with the risk of hiding small areas of ischemia.

Question 30

How can obesity and ascites effect SPECT MPI?

Answer 30

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.

Note: 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.

Question 31

Breast attenuation is likely to create SPECT artifacts which will effect?

Answer 31

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.

Question 32

What are some ways in which we can lower attenuation artifacts?

Answer 32

1. The use of technetium-99–radiolabeled perfusion agents results in less attenuation and scatter and gives higher-quality images than thallium-201.
2. 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.
3. Using gender-matched normal files for quantitative analysis helps to eliminate attenuation artifact.

Question 33

Does type of stress (exercise vs pharm) influence attenuation?

Answer 33

The type of stress does not influence attenuation while the higher background usually seen with pharmacologic stress results in poor image quality.

Question 34

Quantitative analysis of SPECT MPI has been used to help differentiate attenuation artifacts from true perfusion defects. Comparison of a given patient to which of the normal databases gives the best specificity?

Answer 34

Gender-matched normal files improve specificity most by accounting for differences in the amount of breast attenuation.

Question 35

Prone imaging improves SPECT MPI accuracy because it allows recognition of ?

Answer 35

Diaphragmatic attenuation!
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.

Question 36

How does Gated SPECT MPI improve interpretation of SPECT MPI images?

Answer 36

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.

This improves interpretation and reader confidence.

Question 37

How does gated SPECT compare to echocardiography?

Answer 37

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.

Question 38

Which maneuvers is most likely to eliminate liver retention with technetium-99 radiotracers and improve image quality?

Answer 38

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

Question 39

What are some appropriate reason(s) for using pharmacologic stress testing?

Answer 39

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.

Examples:
Peripheral vascular disease limiting exertion
Presence of left bundle-branch block (LBBB) or pacemaker
Failure to achieve target heart rate with dynamic exercise

Question 40

Although vasodilators are generally preferred for pharmacologic stress SPECT MPI, when is dobutamine the most appropriate stress agent?

Answer 40

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.

Note: 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.

Question 41

Why are dipyridamole, regadenoson, and adenosine are effective pharmacologic SPECT stress agents?

Answer 41

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.

Question 42

Which adenosine receptor induces coronary vasodilation when activated?

Answer 42

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.

Question 43

What are some cardiovascular effects of adenosine?

Answer 43

Potent vasodilator
Vagal inhibition at low doses leading to increase in heart rate
Bradycardia and AV block at high doses
Reduced adrenergic activity

Question 44

How is Dipyridamole metabolized?

Answer 44

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.

Note: Adenosine is rapidly taken up by RBCs and has a shorter half life.

Question 45

The side effects reported with adenosine and dipyridamole are due to which receptors?

Answer 45

Adenosine nonselectively activates the adenosine A1, A2B, and A3 receptors that are responsible for the undesirable side effects associated with pharmacologic stress. The stimulation of A2A receptors on arterial smooth muscle cells is what leads to coronary vasodilation.

Question 46

How is Regadeneson different from adenosine?

Answer 46

Regadenoson is a selective A2A receptor agonist. It is the only FDA-approved selective A2A agonist at this time. Following a 10-second fixed bolus injection of 400 mcg over 10 seconds, it produces hyperemia of 2.5 times the baseline blood flow with rapid onset (30 seconds) for a longer period (~2 to 5 minutes) than adenosine, which permits more efficient simplified protocols.

The half-life for regadenoson has an initial intravenous phase of 2 minutes and a longer intermediate phase of 30 minutes and a third phase of 2 hours.

ADVANCE MPI 1 and 2 randomized trials demonstrated noninferiority for regadenoson relative to adenosine for the detection of ischemia. Regadenoson-induced perfusion defects correlated closely with adenosine-induced defects.

Question 47

Compared to adenosine, Regadeneson causes less of what symptoms?

Answer 47

Dyspnea, flushing and chest pain

Question 48

Compared to adenosine, Regedeneson use is associated with more of what symptom?

Answer 48

Headaches

Question 49

In which situations patients should not receive adenosine, Regadeneson or Dypiridimole?

Answer 49

Taking oral dipyridamole
Known sick sinus syndrome
Known high-degree AV block
Taking Aggrenox

Patients taking oral dipyridamole, which is also one of the ingredients in Aggrenox, who receive adenosine, have increased adverse events as the half-life of adenosine is markedly increased over the normal value of <10 seconds. Even though regadenoson is a selective A2A agonist with less stimulation of the A1 receptors that cause AV nodal block, none of the adenosine-stimulating drugs should be used in patients with high-grade AV block without functioning pacemakers.

Question 50

Coronary steal is sometimes described in patients undergoing vasodilator pharmacologic SPECT and PET stress tests. When this phenomenon occurs, it is usually?

Answer 50

Vasodilators do not significantly increase cardiac work or increase oxygen demands but may cause a coronary steal by dilating vessels with noncritical stenoses that are supplying collaterals to areas with high-grade stenosis. This may result in an intracoronary steal due to inadequate flow through the collaterals resulting in an endocardial to subepicardial steal. It is usually associated with clinical symptoms and ischemic ST changes. It can be seen in patients with severe native coronary disease or in patients post bypass surgery.

Question 51

Simultaneous low-level exercise is often used during vasodilator SPECT pharmacologic stress testing. The main advantage of low-level exercise is:

Answer 51

Reducing side effects
Vasodilators used in pharmacologic SPECT stress protocols produce a fourfold increase in coronary blood flow in normal coronaries, which is greater than that achieved with exercise or dobutamine stress. Ischemia is not a requirement to detect heterogeneity in coronary blood flow on the SPECT images. The patients usually undergo a low-level exercise without achieving target heart rate in order to minimize side effects of vasodilators and facilitate the clearance of tracer activity from the liver and gut, which results in better image quality.

Question 52

When using vasodilators for pharmacologic SPECT or PET stress testing, what should we do regarding beta blockers, nitrates and calcium channel blockers?

Answer 52

Beta-blockers, calcium channel blockers, and nitrates can decrease the sensitivity of the test and
should be discontinued if possible 24 hours before the test.

Patients undergoing SPECT or PET MPI on maximal beta-blockers, calcium channel blockers, and nitrates can have normal perfusion studies or a significant reduction in the amount of detected ischemia in comparison to studies performed while off these medications. Thus, for studies performed to diagnose the presence or absence of CAD, these medications need to be discontinued for 24 to 48 hours depending on the formulation.