Challenge: Patient Selection

Appropriate patient selection is critical to ensure the optimal risk versus benefit of MPI, including the type of stress test. As radionuclide MPI is rapidly expanding with conventional SPECT, novel semiconductor detector SPECT, and PET MPI, referring physicians may find it challenging to identify the right test for a given clinical question. Radionuclide MPI and the more recent, multisocietal, appropriate use criteria (AUC) documents provide valuable information regarding the clinical use of radionuclide imaging—SPECT and PET are used interchangeably in the AUC document. The RAND Corporation has defined appropriate use as one wherein the expected clinical benefit of the test outweighs the risks of the procedure, including the radiation risk. The radionuclide AUC were developed based on expert opinion, with the test indications categorized as appropriate, may be appropriate (previous term uncertain ), and rarely appropriate (previous term inappropriate ) by an expert panel. Several clinical studies have confirmed that although most MPI studies (70%–85%) are performed for appropriate indications, a smaller but significant proportion of tests is performed for may be appropriate or rarely appropriate indications. To reduce the use of stress testing in the latter two categories, the Choosing Wisely initiative of the American Board of Internal Medicine (ABIM), in conjunction with Consumer Reports , has listed specific recommendations for physicians and patients to be aware of prior to performing a study; it is summarized as follows:

• 1.
  

  Don’t perform stress cardiac imaging or coronary angiography in patients without cardiac symptoms unless high-risk markers are present.

  
  
• 2.
  

  Don’t perform cardiac imaging for patients who are at low risk.

  
  
• 3.
  

  Don’t perform radionuclide imaging as part of routine follow-up in asymptomatic patients.

  
  
• 4.
  

  Don’t perform cardiac imaging as a preoperative assessment in patients scheduled to undergo low- or intermediate-risk noncardiac surgery.

  
  
• 5.
  

  Use methods to reduce radiation exposure in cardiac imaging, whenever possible, including not performing such tests when limited benefits are likely.

Potential Solutions

A careful review of the reason for the study will ensure appropriate patient selection. This may sometimes involve a discussion with the referring physician to clarify that the clinical question can be appropriately answered by radionuclide MPI or any alternative tests.

An online app (radionuclide appropriateness use criteria) is helpful to evaluate the AUC for any given indication. As of January 2017, Medicare payments have been linked to documentation of AUC in the study report. Several decision support systems now incorporate professional societal AUC criteria into physician order entry systems.

Challenge: Rest Chest Pain

Occasionally, patients referred for a stress test may experience rest chest pain at the time of the test.

Potential Solutions

Examine the patient clinically, ensure hemodynamic stability, and obtain a rest ECG. If clinically unstable, refer the patient to the emergency room for further evaluation.

If the patient has ongoing chest pain but is stable hemodynamically, consider injection of a perfusion tracer (SPECT or PET) during chest pain and rest imaging. In a randomized clinical trial of patients presenting with chest pain to the emergency room, rest MPI, with radionuclide injected during ongoing chest pain or within 3 hours of pain resolution, significantly reduced unnecessary hospitalizations without differences in clinical outcomes. The extent of perfusion abnormality correlated well with the anatomic extent of myocardial ischemia. The sensitivity and specificity of rest MPI performed at <6 hours of the onset of symptoms are >90% and 80%, respectively. However, the reduced specificity is due to lack of differentiation between acute reduction in blood flow versus hibernation or a chronic infarct. The negative predictive value of a completely negative rest MPI in patients with acute chest pain is >99%. Furthermore, resting MPI in these patients has prognostic clinical implications. A positive resting MPI has up to a 30% short-term event rate as opposed to a <1% 30-day event rate for a normal MPI.

If the patient is clinically stable and the rest MPI (during chest pain) is normal, the next step is to proceed with the stress test and imaging. If the rest MPI is abnormal and the patient is clinically unstable, referral to coronary angiography may be warranted. If the patient is clinically stable and has no active chest pain, ¹⁸ F-fluorodeoxyglucose (FDG) PET can be performed. A mismatch between rest myocardial perfusion and FDG metabolic imaging suggests hibernating myocardium as a potential cause for the rest angina ( Fig. 11.1 ).

A 55-year-old woman with known coronary artery disease referred for evaluation of ischemia. (A) At the time of rest image acquisition, the patient complained of typical chest pain, with no electrocardiographic changes. ¹³ N-Ammonia resting perfusion images show a large perfusion defect in the entire inferior and inferolateral walls, with significant mismatch pattern on ¹⁸ F-fluorodeoxyglucose images, suggestive of rest myocardial ischemia. (B) Subsequent invasive coronary angiogram demonstrates a severe proximal right coronary artery in-stent restenosis (arrow).

Challenges During Exercise Stress Testing

During the stress test, patients can experience chest pain, hypotension, ischemic ST segment changes, tachyarrhythmias or bradyarrhythmias, syncope, falls, or other complications.

Potential Solutions

Objective evidence of significant ischemia on the ECG, horizontal or downsloping ST depression (>2 mm), and significant ST elevation (>1 mm; Fig. 11.2 ) are reasons to inject the radiotracer (if feasible) and terminate the exercise, even if the patient is asymptomatic and the age-predicted maximal heart rate (85% of 220 minus age in years) has not been achieved. When significant ST segment elevation is noted during exercise, it localizes the ischemia to a coronary territory. Therefore radiotracer injection and imaging are typically avoided and the patient scheduled for emergent coronary angiography—unless the patient is stable and there is a delay for coronary angiography.

Resting (A) and peak (B) exercise electrocardiograms (ECGs). The peak exercise ECG demonstrates ST segment elevation of >1 mm in leads V3 and V4. (C) Corresponding invasive coronary angiogram image demonstrates a severe (>70%) stenosis of the proximal left anterior descending coronary artery (arrow) .

Subjective complaints of moderate to severe chest pain during exercise may be reasons to terminate exercise. In a patient experiencing exercise-limiting chest pain, if the heart rate is submaximal, the exercise test is terminated, without radiotracer injection. A vasodilator study is performed after the chest pain resolves. Reproducible angina during stress, even in the absence of ECG changes, may warrant additional workup. In hemodynamically stable patients, sublingual nitroglycerin can be administered for moderate to severe chest pain. Persistent or worsening chest pain, even after three doses of sublingual nitroglycerin (0.4 mg) at 5-minute intervals, or hemodynamic instability may be a reason for referral to urgent coronary angiography.

Hypotension, a decrease in systolic blood pressure below the preexercise standing blood pressure, especially when accompanied by other ischemic signs or symptoms, is a marker of underlying significant CAD and death. Exercise-induced hypotension is typically managed by IV fluids and, if necessary, referral to coronary angiography. Nitroglycerin and beta blockers are contraindicated in patients with exercise-induced hypotension.

Symptomatic arrhythmias are managed as per the American Heart Association’s advanced cardiac life support algorithms. Falls or syncope should be addressed immediately with evaluation of hemodynamic status, arrhythmias, and orthopedic limitations and assessment of injuries.

Submaximal Heart Rate Response

Chronotropic incompetence is defined as the inability to attain 85% of the age-predicted maximal heart rate during exercise. It may be related to cardiac disease, medication use (e.g., beta blockers, calcium channel blockers), or orthopedic limitations. The diagnostic accuracy of MPI to identify significant obstructive CAD is limited in patients with a submaximal heart rate response. Therefore if the reason for the MPI is to assess response to medical therapy (as in medically managed patients with CAD), radiotracer may be injected at the heart rate achieved despite submaximal heart rate, especially if a workload of 5 METs (metabolic equivalent of task [or just metabolic equivalent]) is achieved. However, if the reason for the study is to identify ischemia or understand the hemodynamic significance of stenoses of indeterminate significance or preoperative evaluation, a maximal heart rate response is preferred for administration of the radiotracer. Whatever the reason, chronotropic incompetence is a marker of high 2-year mortality, particularly when associated with perfusion defects on MPI. The reasons for high mortality with chronotropic incompetence are not known but may reflect cardiac autonomic function, which may be evident in individuals with advanced heart disease.

Potential Solutions

In patients with submaximal heart rate response to exercise, pharmacologic stress testing (with a vasodilator or dobutamine) is an excellent alternative. Adenosine and dobutamine infusions are typically administered after the treadmill test is terminated. Regadenoson, a novel A2A receptor agonist, is supplied as a prefilled syringe and is not weight-based but can be administered during standard Bruce treadmill protocol when the heart rate is noted to be submaximal, followed by radiotracer injection. When used appropriately, regadenoson with treadmill exercise is safe and yields a result similar to that with vasodilator stress without exercise.

Challenges During Pharmacologic Stress Testing

In carefully screened and selected individuals, adverse effects during pharmacologic stress testing are uncommon. Severe chest pain, ischemic ECG changes (ST elevation >1 mm in non–Q wave leads or >2-mm ST depression in three consecutive beats), hemodynamic instability (decrease in systolic blood pressure <90 mm Hg), signs of poor perfusion (e.g., pallor, cool extremities), high-degree AV block ( Fig. 11.3 ), wheezing, atrial or ventricular tachyarrhythmias or bradyarrhythmias, or intolerance to the infusion have been reported. Low-grade exercise with vasodilator infusion can attenuate side effects and improve image quality by reducing the subdiaphragmatic uptake of the tracer.

(A) Normal sinus rhythm at baseline. (B and C) Complete atrioventricular node block seen during adenosine infusion (p waves [blue arrows] , followed by no QRS complexes), with resolution of the block after discontinuation of the infusion (D).

Potential Solutions

Mild side effects are common and usually well tolerated. Moderate to severe adverse effects during adenosine or dobutamine infusions may necessitate premature termination of the infusion.

Infusion of regadenoson (administered as a bolus over 10 seconds) or dipyridamole (administered over 4 minutes but with symptoms occurring at 7 minutes) typically is not terminated, but the hyperemia is counteracted by IV aminophylline.

Aminophylline (50–150 mg slow IV push, 1–1.5 mg/kg) given as a slow IV bolus over 60 to 90 seconds can be used to reverse the hyperemic effects of vasodilator agents. Due to the short half-life of adenosine, aminophylline is not typically needed unless the patient has wheezing or prolonged heart block, despite termination of the adenosine infusion.

For hypotension, IV fluids may be administered (100–150 mL of normal saline IV as a rapid bolus), followed by IV aminophylline, as described above.

Chest pain typically resolves with termination of the infusion agent and after IV aminophylline. If chest pain persists, especially with ST depression, sublingual nitroglycerin, 0.4 mg, can be administered, provided that the systolic blood pressure is >90 mm Hg and there is no recent history of the use of sildenafil or other phosphodiesterase inhibitors. IV beta blockers (5 mg IV metoprolol [Lopressor] over 30 seconds) can be administered for chest pain, especially during dobutamine infusion.

Wheezing is managed with inhaled albuterol via a nebulizer every 10 minutes, as needed. If wheezing does not improve after two units of nebulizer therapy with albuterol have been administered, consider referral to the emergency room.

High-grade AV block, usually transient, is common with IV adenosine infusion, especially following radiotracer injection at 2 minutes into the infusion. Exercise, hand grip, or supine leg exercise typically improves the heart block. In patients with persistent or symptomatic high-grade AV block, adenosine infusion may be prematurely terminated. Persistent or symptomatic heart block, although less frequent after termination of the adenosine infusion or with dipyridamole or regadenoson, is managed with IV aminophylline.

In cases of hemodynamic instability, signs of hypoperfusion, or sustained ventricular arrhythmias, advanced cardiac life support measures are instituted.

The Challenge

Attenuation of the photons from the patient’s body, typically because of a large body habitus, breast tissue in females, and muscular diaphragm in males, or from arms-down imaging, is a major source of artifact with radionuclide MPI ( Figs. 11.4–11.6 ). Breast tissue typically reduces counts in the anterior or lateral wall of the left ventricle, depending on the size and position of the breasts. Although more often these so-called defects appear fixed, a shift in breast tissue position (especially the left) between the rest and stress scans can produce an apparently reversible perfusion defect (see Fig. 11.4 ). Inferior wall attenuation is seen more commonly in men due to attenuation from a muscular diaphragm (see Fig. 11.5 ).

Rest and stress ^99m Tc- SPECT perfusion images of a 70-year-old woman for evaluation of atypical chest pain. There is a small, mild-intensity, fixed perfusion abnormality in the mid- to apical anterior-anteroseptal wall. Gated images (not shown) showed normal wall motion and thickening, consistent with a breast attenuation artifact.

Rest (A) and stress (B) supine images in a 56-year-old man show reduced counts in the inferior wall. Gated images (not shown) showed normal wall motion and thickening. With prone imaging (top row in B), an increase in the inferior wall counts is seen, confirming the diaphragmatic attenuation.

Arms down during stress images as seen on rotating projection images, leading to attenuation and reduced counts on the sinogram (arrows) .

Identifying the Artifact

A careful review of the raw rotating planar and projection images will help identify attenuation from breast tissue or from the diaphragm. It is also important to identify breast tissue on the stress and rest images to ensure that they are in a similar position.

Potential Solutions

If breast tissue attenuation is the suspected cause of a fixed perfusion defect, gated SPECT, repeat imaging, and attenuation correction can be considered.

The Challenge

Patient motion during MPI is an important and common source for artifacts with both SPECT and PET MPI. Motion can be vertical, horizontal (side to side), or complex. Motion may also be gradual or abrupt. A 0.5-pixel movement does not cause a detectable defect, whereas a 1- pixel movement could cause a defect that is detectable but may not be clinically significant; motion of 2 pixels or more causes a clinically significant artifact. With the newer cardiocentric scanners, the acquisition is quick and, due to the reduced scan time and more comfortable position, the frequency of patient motion may be reduced. Patient motion during the transmission scan may also be a significant source of artifacts.

Identifying Patient Motion

Traditional Anger SPECT Scanners

With traditional SPECT, images are acquired in a temporal sequence using a multiframe acquisition (step and shoot or continuous), with a series of 32 to 34 image frames acquired by each scanner detector, for a total of 60 to 64 frames. A review of rotating projection images can identify patient motion, especially vertical or complex motion. The sinogram may be better at identifying horizontal motion, and a linogram can further provide information about motion ( Fig. 11.7 ).

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