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Volume 3 Issue 6 - June 2005
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Nuclear Cardiology Stress Tests for Coronary Artery Disease

  • Exercise ECG without imaging should be the first choice for evaluation of coronary artery disease (CAD) when patient can exercise on a treadmill to 85% of maximum predicted heart rate and
    • resting ECG is normal or has minor abnormalities
    • unstable myocardial infarction (MI) has been ruled out
    • risk of adverse effects from exercise is low to intermediate


  • Cardiac stress myocardial perfusion SPECT is indicated:
    • when baseline ECG suggests that exercise ECG would be nondiagnostic or uninterpretable for ischemia    
    • when clinical presentation and exercise ECG indicates at least an intermediate likelihood of CAD
    • for preoperative evaluation of those with known high coronary risk factors
    • for management of known cardiac disease


  • Physical exercise stress myocardial perfusion SPECT is recommended if patient can exercise to 85% of maximum predicted heart rate; otherwise pharmacological stress myocardial perfusion SPECT should be ordered


Myocardial Perfusion Imaging SPECT (MPI SPECT)
Stress Myocardial Perfusion Imaging SPECT
Limitations of MPI SPECT
Patient Preparation
Test Procedure
Myocardial Perfusion Imaging PET (MPI PET)
Scheduling
Further Information
References

W
hen patients present with chest pain, clinical examination and patient history are fundamental to determine the probable cause of pain and the selection of appropriate tests to confirm clinical suspicions. In the case of myocardial ischemia due to coronary artery disease (CAD), the patient often but not always presents with the classical symptoms, chest tightness and left arm pain. However, cardiac symptoms may be similar to indigestion, muscle spasm, or other non-specific complaints. Nevertheless, other causes of chest pain that do not have cardiac origin, including pulmonary embolism, pneumothorax and aortic dissection must always be considered.

If CAD is suspected after these initial examinations and MI or severe unstable angina has been ruled out along with other dangerous but non cardiac causes of chest pain, the next step is exercise ECG (exercise treadmill test, ETT), provided that the patient is able to exercise well enough to reach 85% of maximum predicted heart rate (HR; 200-age is 100% of the patient maximum predicted HR) and has a normal resting ECG or has only minor ECG abnormalities that will not interfere with interpretation of the exercise ECG (See Box 2).

Myocardial Perfusion Imaging SPECT
(MPI SPECT)

Although nuclear cardiology is both time consuming and expensive, MPI SPECT is valuable for the clarification of a suspected false positive (or negative) exercise ECG. It is also a valuable test for patients with an intermediate likelihood of coronary artery disease if the patient is unable or unwilling to perform an exercise ECG. MPI SPECT has major utility to define the extent and location of disease, determine the physiological significance of known coronary stenoses, evaluate a particular vascular territory, and to risk stratify a patient with known or suspected CAD once an unstable acute coronary syndrome has been excluded. Therefore, MPI SPECT is well established for prognostic evaluation of these patients.

MPI SPECT is also valuable for the management of patients with cardiac disease, for example, to assess viability and to guide the selection of by-pass graft or
 
(Box 1) Contraindications for Nuclear Cardiology
Stress Test

Absolute
Acute myocardial infarction
Severe aortic stenosis
Severe reaction to stress agent
Severe pulmonary hypertension
Obstructive hypertrophic cardiomyopathy
Combination of low EF (20%) and
--documented recent VF/VT
Cocaine within 24 hours
Pregnancy
Unstable angina

Relative
Severe Mitral stenosis
Hypertension (>180/100 mm Hg)
Hypotension (<90 mm Hg, systolic)
Tachycardia (>120/min)
Wheezing, bronchospasm
Unable to communicate
Acute illness such as pericarditis, pulmonary
--embolus, infection, fever


PCI (percutaneous coronary intervention) region. In addition, the left ventricular ejection fraction, which is obtained as an integral part of the MPI SPECT study, is an important determinant of long-term prognosis and can be used to evaluate symptoms such as shortness-of-breath, fatigue, and poor exercise tolerance.

Nuclear cardiology images show the distribution of a radioactive agent, such as 99mTc-Sestamibi. Since the amount of radioactivity is roughly proportional to regional blood flow, nuclear cardiology images show variations in blood flow in the myocardial regions that are under-perfused relative to other regions and may be the cause of myocardial ischemia. Additional information on cardiac function, such as ventricular motion and ejection fraction, can be obtained when cardiac gating is used to synchronize image acquisition to the cardiac cycle.

In most cases, blood flow is adequate in the resting state but not during exercise or physiological stress because diseased blood vessels are unable to dilate further in response to increased energy demand. Therefore, nuclear cardiology images are acquired both under stress and rest conditions to unmask the reserve capacity of the coronary blood vessels. However, resting SPECT MPI may be ordered as a separate stand-alone study (i.e. rest gated MIBI) to assess left ventricular ejection fraction, regional contraction and myocardial viability (not for ischemia).

 
MPI SPECT findings consistent with inferior and inferolateral ischemia with an incomplete infarction in these areas.


(Box 2) Recommended Tests for Intermediate or High Likelihood of CAD
I. Patient Able to Exercise (to at least 85% maximum predicted heart rate),
Normal or mildly abnormal resting ECG
Not taking digoxin
Stress ECG
Abnormal ECG that interferes with interpretation of
--stress ECG:
Ventricular pre-excitation
>1 mm ST depression
Left ventricular hypertrophy
To evaluate physiological significance of coronary
--stenoses (25-75%)
Intermediate Duke treadmill score
High risk patients (>20% of 10 yr risk of cardiac event)
Selected high risk asymptomatic patients, 3-5 yrs after
--revascularization

Resting and exercise myocardial perfusion SPECT

Cardiac pacemaker
Left bundle branch block

Resting and adenosine or dipyridamole stress myocardial
--perfusion SPECT

II. Patient Unable to Exercise
To evaluate extent, location, and severity of ischemia
To evaluate physiological significance of coronary
--stenoses (25-75%)
Known CAD, change in symptoms suggest increased
--likelihood of cardiac event
High risk patients (>20% 10 yr risk of cardiac event)
Selected high risk asymptomatic patients, 3-5 yrs after
--revascularization
Resting and adenosine or dipyridamole stress myocardial
--perfusion SPECT
Severe COPD, recent (<1 month) asthma attack
2nd and 3rd degree of AV block
Severe bradycardia <40/min
Adenosine and dipyridamole contraindicated
Resting and dobutamine stress myocardial perfusion SPECT
III. Indications for PET
SPECT study equivocal
Obesity (>400 lbs)

Resting and adenosine or dipyridamole or dobutamine
--stress myocardial perfusion PET



Stress Myocardial Perfusion Imaging SPECT
If the patient is able to exercise to at least 85% predicted maximum heart rate, an exercise stress MPI SPECT should be performed.

If the patient is unable to exercise, a pharmacological stress MPI SPECT can be performed by the injection of agents (adenosine, dipyridamole) that cause vasodilatation or mimic exercise pharmacologically (dobutamine). Both exercise and pharmacological stress tests have equal diagnostic accuracy and physiological pharmacological stress is fast, safe, and reproducible.

Limitations of MPI SPECT
SPECT myocardial imaging is subject to potentially misleading soft tissue attenuation artifacts in people who are obese, women with large breasts, and men with increased abdominal girth as in the Metabolic Syndrome. Patient specific attenuation correction can be utilized but may lower sensitivity. In addition, SPECT images only show relative blood flow, not absolute flow, from the intensities of the regional radioactivity. Therefore, it is possible to miss CAD if all three branches of the coronary arteries are occluded and reduce the flow to a similar extent. Overall, the test sensitivity is 87% and the specificity 78%.
  Patient Preparation
Since ß-blockers slow the heart rate and the stress test is designed to increase heart rate, it is preferable that ß-blockers be withdrawn prior to cardiac stress myocardial perfusion SPECT to ensure that arterial pressure increases appropriately with exercise if the test is ordered for diagnostic purposes. The patient should be warned to reduce his/her level of exertion and his/her physician must, of course, determine that it is safe and appropriate to do so. Unfortunately, sudden withdrawal of ß-blockers may cause a surge in blood pressure, which could result in test cancellation. Therefore physicians should withdraw them slowly and monitor blood pressure to be certain that the patient can complete a stress test. Other anti-hypertensive medications may be continued to avoid excess hypertension at the time of the test. Anti-anginal agents may be continued with the referring physicians approval. If physicians want to establish the effectiveness of medication, they may continue the medication to evaluate the symptoms and ischemic territory and size with stress test MPI SPECT.Patients should not consume any caffeine or chocolate 24 hours prior to the test and should not eat, drink, or smoke for 12 hours prior to the test. Therefore, diabetics, in consultation with their PCP or endocrinologist, should adjust their insulin and other anti-diabetic medication accordingly.


Test Procedure
The procedure begins with an intravenous injection of radionuclide contrast agent with the patient at rest. Twenty to thirty minutes later, when the radionuclide is distributed throughout the body, the patient is imaged with a gamma camera for a period of 20-30 minutes to obtain baseline cardiac images. If an exercise stress test is to be done, the patient will be taken to a treadmill and asked to exercise while their ECG is monitored. One minute before the patient has reached his or her limit or HR has reached 85% of the predicted maximum, a second dose of radionuclide contrast is injected and exercise continued for one more minute. After another 30 minute wait for the radionuclide to equilibrate, the patient is imaged for a second time to obtain stress myocardial images.

If a pharmacological agent is used to induce coronary dilation, the second injection of radionuclide contrast is injected at 10 minutes after injection of dipyridamole or 2 minutes into the infusion of intravenous adenosine. The stress images are obtained after radionuclide equilibration, as above.  The total time for the procedure is 3 – 3.5 hours.

A radiologist and cardiologist will examine the series of SPECT images in the short axis, the horizontal long axis, and the vertical long axis to assess perfusion defects. In addition, the cardiac-gated SPECT images may be reconstructed into cine loops, which are used to assess regional ventricular wall motion, ejection fraction, and, indirectly, myocardial viability.

Myocardial Perfusion Imaging PET
(MPI PET)

MPI PET can be performed when MPI SPECT is equivocal or likely to be uninterpretable because of obesity. PET is a quantitative modality because tracer kinetic models can be applied to the data and attenuation artifacts largely avoided. It can therefore help detect false negative or positive MPI SPECT results. MPI PET should be ordered with prior consultation of a nuclear cardiologist.

 
(Box 3) Possible Complications of Stress Test
Exercise
Chest pain, 20%
Cardiac event, 0.01-0.02%
Death, 0.002% or 1/50,000
Accidental fall
Pulmonary edema
Pharmacological (adenosine)
Chest pain, 20-40%
Some degree of AV block, 3-18%
Bradycardia, 12%
Nausea, 5%
Drop in BP, 3-5%
Bronchospasm, 0.2%
Cardiac event, death, <1%


Scheduling
Appointment for nuclear cardiology examinations may be scheduled by calling 617-643-1552 or through the Radiology Order Entry system, http://mghroe . Weekend scheduling should be made directly by calling the on call nuclear cardiologist at 617-726-9292.


Further Information
Further information may be found on the Nuclear Cardiology website. For questions, please contact James Scott, M.D. , Associate Professor of Radiology.

We would like to thank Henry Gewirtz, M.D., Associate Professor of Medicine and Director of Nuclear Cardiology, and Hiro Yasuda, M.D., nuclear cardiologist, for their assistance and advice for this issue.




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References
   

Crean, A, Dutka, D and Coulden, R. (2004) Cardiac imaging using nuclear medicine and positron emission tomography. Radiol Clin North Am 42: 619-34

Expert Panel on Cardiovascular Imaging: Stanford W, Bettmann, MA, Boxt, LM, et al. American College Of Radiology ACR Appropriateness Criteria™; Acute Chest Pain—Suspected Myocardial Ischemia. Available at http://www.acr.org/ac_pda. Accessed: 6/2005.

Klocke, FJ, Baird, MG, Lorell, BH, Bateman, TM, et al. (2003) ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation 108: 1404-18