Sources of False Positive (Slow washout rates of Tl-201)
  1. Low exercise heart rate
    1. Uptake and washout are based on coronary blood flow
    2. Submaximal stress test causes reduced blood flow which relates to reduced washout rate
    3. Stress tests that reach 85% or greater will have increased washout rates

  2. Subcutaneous infiltration of Tl-201 (MIBI?)
    1. Causes slow release of Tl-201 into the blood stream after the patient has been stressed
    2. Recommend an IV always be established when injecting the stress dose

  3. Arm Vein Uptake of Tl-201
    1. Study showed 53% vein uptake when the dose was not injected into the medial antecubital vein
    2. Saline flush does not reduce vein uptake
    3. Results in gradual release of Tl-201 into the blood stream after the patient has been stressed
    4. Lower and delayed peaking of Tl-201 in the myocardium causes a slower washout rate

  4. Low count rate studies
    1. Lower the count rate the greater the counting error
    2. Must have enough counts in planar and SPECT imaging
    3. Significant tissue attenuation may also reduce the amount of counts acquired for the study

  5. Inappropriate data acquisition (planar)
    1. Always acquire for the same amount of time
    2. Do not increase your time for acquisition from stress to the delayed views

  6. Protocol deviation
    1. Always inject the patient at maximum stress and continue to stress the patient for one additional minute
    2. Variations from this critical point may cause the dose to be delivered to the myocardium without maximum hyperemia being achieved
    3. Imaging sequence is also important in planar imaging and should always be: ANT, LAO 45, and steep LAO. Otherwise, a false positive washout curve may result

Detection of Coronary Artery Disease
  1. Sensitivity and Specificity
    1. Planar Tl-201 is 82% sensitive and 88% specific
    2. Combination of the literature indicated a mean sensitivity of 86% and a mean specificity of 85%
    3. 79% sensitivity with patients that did not have a prior infarct
    4. 96% sensitivity with patient that have had a previous infarct

  2. Referral bias
    1. May increase sensitivity and reduce specificity
    2. Sensitivity and specificity should be determined by sampling a population
    3. Bias occurs because all abnormal studies are sent to cardiac catheterization

  3. Amount of stenosis and coronary vessels affect sensitivity
    1. Single vessel disease = 79%
    2. Double vessel disease = 88%
    3. Triple vessel disease = 92%
  4. Pharmacological stressing has similar results to treadmill stress testing

  5. Quantifying the images seems to improve sensitivity and specificity

  6. In SPECT imaging (and quantitative analysis)

    1. Sensitivity appears to increase slightly while specificity seems to decrease slightly
    2. This may be caused by referral bias
    3. One study showed that SPECT was superior
      1. In male patients
      2. Milder disease with no previous infarct
      3. Single vessel disease where the artery was 50-69% stenotic

  7. Bayes' theorem and its application in nuclear cardiology
    1. Two questions must first be considered
      1. What is the probability of the patient having disease if the results are positive?
      2. What is the probability of the patient not having disease if the results are negative?
    2. Initially determine the pre-test likelihood of disease - setup parameters
      1. Asymptomatic
      2. Chest pain = substernal location, provocation by exercise, and pain relief via nitroglycerin
        1. Typical angina = all the
        2. Atypical angina = two of three
        3. Non-angina = one of three
    3. Pretest likelihood of disease affects the post-test likelihood of disease
      1. In an asymptomatic patient, pretest probability of having diseases is 5%. The results then indicate only 20% that have a positive stress test are truly positive, while less than 1% of the negatives are false negative
      2. In classifying those patients with an intermediate likelihood of CAD the pretest probability is 50%. [post test] Of those patients that have a positive test, 90% will be true positives, while those that are negative have less than 10% of being false negative
      3. High pretest likelihood (typical angina) of CAD has a 90% likelihood of disease. [post test] Of those that are positive 99% are true positive, while of those that have a negative scan, 75% are false negative
      4. Conclusion:
        1. Does a nuclear cardiology exam benefit patients with low probability of disease?
        2. When should nuclear cardiology be ordered on a patient?
        3. Of the classifications above, which group of patients receives the most benefit when Bayes' theorem is applied?
        4. What is the value of taking a patient's history?
    4. A little more information on sensitivity/specificity/accuracy
      1. True-positive = sensitivity
      2. True-negative = specificity
      3. Sensitivity + specificity = accuracy

  8. Detection of disease in coronary arteries
    1. LAD, LCX, RCA
      1. Sensitives are 69%, 37%, and 65% respectively
      2. Specific 94%, 95%, and 85% respectively
    2. Comments on why Tl-201 has low sensitivity
      1. In patients with multivessel disease
        1. More than one area will be ischemic, however, only the more hypoperfused area is identified. Inability to identify all the regions may relate to the variations of count density and the contrast between the different regions of perfusion
        2. The stress test may be terminated at sub-max due to ischemic developments. The area that caused the ischemic event will be identified; however, if other area(s) exist that would cause ischemia, but is/are not as stenotic as the one that caused termination of the stress test, then blood flow to the less stenotic areas may appear normal. Hence, the importance of achieving maximum heart rate is essential in order to define all ischemic areas
        3. 50% or less narrowing of a coronary does not lead to ischemia or hypoperfusion, but can be seen in angiography
        4. Collateral circulation may prevent an area from becoming ischemic
    3. Quantification of planar imaging has improved sensitivity and specificity
    4. SPECT and its role with detecting CAD
      1. LAD - 75% and 85% respectively
      2. LCX - 54% and 97% respectively
      3. RCA - 88% and 84% respectively
      4. Quantification seems to improve sensitivity, but not specificity
      5. Overall SPECT improves sensitivity, which may be due to improved contrast defining the defect and decreasing the overlapping of the myocardial walls (when compared with planar)
    5. Multi-vessel disease
      1. When all three vessels contain disease, hypoperfusion to the entire LV may show uniform uptake, and indicate a false negative study
      2. Quantitative analysis may improve the detection rate of multi-vessel disease (looks at the washout curves)
      3. One aspect to note with visual analysis is to determine if the walls to the are LV very thin
      4. Pulmonary uptake of Tl-201
        1. Increased pulmonary uptake can be related to left ventricular dysfunction or multi-vessel disease
        2. Draw ROIs around the lung activity at stress and redistribution
        3. Compare (ratio) to determine the extent of the washout rate from the pulmonary system
        4. Slow washout may also be due to: mitral valve regurgitation, mitral stenosis, decreased left ventricular compliance, and non-ischemic cardiomyopathy with left ventricular dysfunction
      5. Transient Ischemic Dilation of the LV
        1. Multi-vessel or critical stenosis of two or more coronary arteries causes LV transient dilation
        2. Ratio of stress to rest image (negative for ischemia) is 1.02 +/- ).05
        3. Ratio of stress to rest images (two vessel disease) is 1.12 +/- .08
        4. Ratio for stress and rest images (three vessel disease) is 1.17 +/- .09

  9. Assessment of myocardial viability (Tl-201) in patients with chronic CAD
    1. Studies have shown that 3-4 hour redistribution images that seem as non-reversible may become reversible in 18 to 24 hours.
    2. One study showed segmental reversibility improved following by-pass and angioplasty
    3. Another study analyzed late reversibility and identified segments that were considered non-reversible. It concluded that at least 1 segment in 53% of the patients had late reversibility
      1. - Cause may be due to glucose loading
        2. OR
      2. - Low regional myocardial blood flow in areas that have severe stenosis

Assessment of Prognosis

  1. Patients without MI -- predicting a future cardiac event (MI)
    1. Normal or equivocal nuclear cardiology scans have low cardiac event rates
    2. One study showed that if one or more myocardial segments had "moderate" defect(s), 10.7 out of 100 patients would have a cardiac event within a year
    3. Cardiac event rates increase exponentially with increasing severity of the defect
    4. The extremes
      1. Patients with normal exercise Tl-201 stress test (reached 85% stress level) and who had a normal scan averaged a 1% cardiac event rate within one year
      2. Patients who did poorly on the stress test and had severe and extensive reversible defect averaged 78% cardiac event rate within one year
    5. Comparing medical treatment to by-pass surgery, only patients that had two or more reversible defects reduced his/her cardiac event rate if treated with by-pass surgery. Patients that had only one reversible defect that were treated via medication or by-pass surgery indicated that neither method reduced the cardiac event rate
    6. Size of the defect also correlates to the probability of a cardiac event. The larger the defect, the greater an event is likely to occur.
    7. Other indications of increasing the cardiac event rate include: Tl-201 pulmonary uptake, heart-to-lung ratios, history of typical angina, prior MI, and exercise ST segment depression
    8. Another study suggested that the two most significant predictors to a cardiac event were: (a) the number of vessels that were stenotic (>/= 50%) and (b) the amount of Tl-201 segments that had reversible defects

  2. Patients with MI -- predicting a future cardiac event
    1. One study showed that if two non-reversible defects, coupled with the presence of reversible defect and abnormal heart-to-lung ratio with Tl-201 were highly predictive of a cardiac event
    2. In a study, where dipyridamole was used to stress the patient, Tl-201 was administered to patients that had a previous MI. Of the 33 patients that had reversible defects, 11 died or had a recurrent MI during the following 19 month. Only one patient of 18 (6%) had a cardiac event, in which the dipyridamole study identified no reversible defects
    3. Finally, submaximal exercise using a treadmill was performed with a small group of patients, who were then subsequently administered with dipyridamole Tl-201. Results indicated that the dipyridamole/Tl-201 was a better predictor of a cardiac event as compared to just the exercise electrocardiogram

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