1. Tagenarayan Niwaz
January 23, 2015

2.  Two major goals of testing:
 Diagnosis
 Absence or presence of CAD
 Prognosis
 Determine long-term prognosis or the
risk for an adverse outcome over time

3.  The performance characteristics of
radionuclide imaging for diagnosis
often are based on an angiographic
definition of stenosis of ≥50 or 70%
stenosis in epicardial vessel
 CAD - more complex process
 Plaque progression/growth
 Stable  unstable plaque transition
 Exertional angina/potential for ACS

4.  With evolution of preventive measures, testing
has shifted toward assessment of CV risk
and predicting future events
 Risk stratification and assessment of prognosis
by noninvasive imaging –
 reducing risk of MI and cardiac death
 optimizing the selection of patients for
revascularization vs medical therapies

5.  Goal is to detect patients at risk for:
1. “Hard” cardiac events
 Nonfatal MI, cardiac death, all-cause
mortality
2. “Soft” cardiac events
 Revascularization, hospital admission for
unstable angina or CHF
 More common than hard events

6.  Low risk - <1% per year risk of hard cardiac
events
 Least likely to benefit from revascularization strategy
 Benefit from medical therapy, risk factor modification
 Intermediate risk - 1% to 3% per year risk
 High risk - >3% per year risk
 Most likely to benefit from revascularization strategy

7. Extent of perfusion abnormality by stress MPI - important
relationship with subsequent likelihood of an adverse natural
history outcome. A = small defect. B = large defect

8. Incremental
Prognostic Value
N = 2,200 patients
MPI  Further risk
stratification

9. Revascularization better if >10% of ischemic myocardium involved
N= 10,000 patients with suspected CAD studied by stress MPI

10.  Normal study - hard event rate (i.e., rate of
cardiac death or nonfatal MI) occurring during
an average follow-up period of 2 years is
0.7% per year
 Low-risk outcome after a normal MPI study extends
approximately 2 years after testing
 Higher risk in pts w/ prev risk factors (DM, smoking)
 Seen with a board spectrum of isotopes, protocols,
and stressors

11.  If CAD is present by CATH w/ stable
symptom complex, a normal stress MPI
study result is associated with a low-risk
outcome (Approx 0.9% per year)
 Why normal MPI?
 Preserved endothelial function, allowing
appropriate flow-mediated vasodilation during
stress, reduced impact stenosis on downstream
myocardial perfusion
 Preserved endothelial function - less
susceptible to plaque fissuring or rupture

12.  Another mechanism may involve the presence
of collateral circulation, allowing normal
stress perfusion in the setting of a stenosis,
and protecting against infarction should the
stenosis become completely occluded

13.  PET or SPECT assessment - improvement in
stress perfusion after statin therapy
 No change in degree of luminal stenosis but due to
statin-mediated improvement in endothelial
function
 Changes in perfusion – define patients that can
gain benefit from statin therapy in terms of
vascular stability
 Long term follow up needed

14. Extent Of Ischemia
After Statin

15.  Angiography - gold standard to detect CAD
 Accuracy of noninvasive testing is based upon:
 Sensitivity
 Percentage of true-positive test results among those with
CAD as defined by angiography
 Specificity
 Percentage of true-negative test results among subjects
without CAD

16.  Coronary atherosclerosis - complex disease
process
 Involving the coronary arteries diffusely and not
focally
 Underlying disease still present
 Whether a discrete stenotic lesion seen at rest
during Cath results in a perfusion abnormality
during stress
 1. Dependent on the percentage degree of stenosis
 2. Dilatory or constrictor response of the vessel
during stress (mediated by endothelial function)
 3. Presence or absence of collaterals

17.  Epicardial vessel with 70% stenosis but preserved
endothelial function and collateral supply may have a
normal stress MPI
 False-negative finding b/c CAD exist, reduced MPI
sensitivity
 MPI data - correct physiologic information with
adequet blood flow reserve despite coronary
stenosis
 This example illustrates the limitation of using
angiography as a gold standard in evaluation of a
physiologic modality

18.  Isolated septal reversible perfusion defects
 Due to flow between the LAD and LCx territories 2/2
to delayed relaxation of the septum in LBBB leading
to reduced coronary flow reserve in early diastole
 See in pts w/ LBBB w/o stenosis of the LAD
 Decrease specificity and predictive value of a septal
perfusion defect with LBBB
 Apical or anterior involvement in septal perfusion
defects increases the specificity for CAD
 Septal defect in LBBB – seen w/ high heart
rates  pharmacologic stress improves
specificity

19.  Asymmetric septal hypertrophy – seen in HCM,
appearance of greater amount tracer uptake in the
hypertrophied septum relative to the lateral wall
 Lateral wall perfusion defect
 Asymptomatic patients with HCM – can have inducible,
reversible perfusion abnormalities in the absence of
CAD, typically involving the septum
 Possibly related to microvascular abnormalities
 Unfavorable prognosis

20. Apex consistent with infarction
Hypertrophied septum
Silent Ischemia In The Anterior, Lateral,
And Inferior Wall in HCM

21.  MPI perfusion abnormalities – can develop in
patients with pressure overload LVH related
to either hypertension or aortic stenosis
 In the absence of CAD – may represent regional
myocardial ischemia based on abnormal
microcirculation and limited vasodilator reserve
 Accuracy of MPI w/ LVH to detect CAD = to pts
without LVH
 ACC/AHA Guidelines: Class I indication for CAD
detection when LVH present

22.  Abnormalities MPI - common in
patients with dilated
cardiomyopathy despite normal
epicardial coronary arteries
 Likely a result of abnormal coronary
flow reserve
 Worse prognosis, even in the absence
of CAD

23.  LV systolic dysfunction – MPI help
distinguishing those w/ cardiomyopathy due to
CAD (potentially reversible LV dysfunction) vs
those with Idiopathic, Non Ischemic Dilated
Cardiomyopathy
 Normal MPI  usually excludes CAD as the cause
of the cardiomyopathy
 Abnormal MPI  usually associated with CAD
rather than with Non Ischemic Dilated
Cardiomyopathy

24. • MPI Stress/Rest in a patient with LV Dysfunction – low
likelihood of CAD

25.  Abnormalities in myocardial perfusion detected by
SPECT MPI have been demonstrated in patients
with coronary endothelial dysfunction w/o
“significant” epicardial stenosis
 These findings represent true abnormalities in
coronary flow reserve
 Improvement in perfusion on follow-up MPI after
treatment with medical therapies directed at improving
endothelial function
 Data from Cardiac MRI - demonstrating blunted
subendocardial coronary flow reserve in
patients with angina and normal coronary arteries

26.  2003 ACC/AHA/ASNC Radionuclide Imaging
Guidelines Sensitivity and Specificity
 Metanalysis - 33 studies; 4,480 patients w/ exercise
SPECT imaging
 Sensitivity to detect CAD is 87% (range, 71% to
97%)
 Specificity to rule out CAD is 73% (range, 36% to
100%)
 Limited incorporation of ECG-gated SPECT imaging
of regional function or attenuation correction
 Enhanced specificity

27.  201Tl (thallium) vs 99mTc-sestamibi - no
significant improvement in sensitivity or
specificity
 Exception - improved specificity in women
with 99mTc-sestamibi vs 201Tl
 99mTc-based agents - greater photon
energy,
 Better for obese patients and those with large
breasts
 Higher-quality gated images

28.  Intraobserver and Interobserver variability
in the visual analysis of myocardial
perfusion images can occur
 Quantitative analysis of MPI
 Developed to reduce the variability in reading
by
 “Objectifying” image analysis by comparing
regional uptake values against a database of
normal values
 Emory Toolbox,1 Cedars QPS,60 and 4D-
MSPECT

29.  Compared:
 4DMSPECT (4DM), Emory Cardiac Toolbox (ECTb),
and Cedars Quantitative Perfusion SPECT (QPS)
 N= 1,052 consecutive pts w/ 2-day stress/rest
99mTc-sestamibi MPS studies
 Reference classifications - three physicians, w/
> 25 years of experience in nuclear cardiology
Conclusion: 4D-MSPECT showing the best
performance and Emory Toolbox,1 the worst

30. Large apical reversible defect

31.  Sensitivity and Specificity of vasodilator
pharmacologic stress combined with MPI
for the detection of CAD
 Similar to exercise stress
 Lexiscan MPI = Treadmill MPI
 2003 ACC/AHA/ASNC Radionuclide
Imaging Guidelines
 2,465 Patients and 17 studies
 Sensitivity of 89% and specificity of 75%

32.  Dobutamine Stress- similar to
pharmacologic and exercise stress
modalities for the detection of CAD
 Downsides: Maximal coronary flow reserve is
not achieved as often as with vasodilator
stressors and side effects
 Hence, dobutamine recommended only when
adenosine, dipyridamole, or regadenoson is
contraindicated
 Reactive airways disease

33.  Sensitivity of MPI highest when the
highest possible level of oxygen demand
is achieved to stimulate the greatest
coronary flow reserve
 For exercise ECG testing - sensitivity
decrease if maximum predicted heart
<85% not achieved
 If unable to reach goal, convert to
pharmacologic test

34.  Perfusion changes occur at lower degrees of
supply-demand mismatch vs EKG changes
 Sensitivity of MPI to detect CAD seen maintained at
lower workloads
 Pts with CAD - stressed with MPI at a maximal
workload and then again at submaximal workload
 No difference in sensitivity between the maximal and
the submaximal tests
 Extent and severity of reversible perfusion defects were
diminished at submaximal compared with maximal
workloads

35.  Exercise is the preferred stressor
 Allows for association of symptoms
with perfusion abnormalities
 Incorporation of validated stress test
criteria
 Duke Treadmill Score, heart rate reserve,
or heart rate recovery with the MPI data