This document discusses the approach and methodology for myocardial perfusion scans. It covers pretest probability assessments, stress testing criteria and risk levels, radiotracers used, imaging protocols, interpretation of scans, and initial analysis of images. The key points are: - Stress testing is used for diagnosis and risk stratification of coronary artery disease. Various protocols and radiotracers like Tc-99m are discussed. - Images are interpreted by evaluating perfusion defects, ventricular sizes, lung/RV uptake and quantitative analysis. - Initial analysis involves assessing ventricular dilation, lung uptake, and right ventricular uptake which can provide clinical insights.

1. Approach to
Myocardial
perfusion
scan
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• Coronary revascularization is appropriate when the expected
bene
fi
ts, in terms of survival or health outcomes (symptoms,
functional status, and/or quality of life) exceed the expected
negative consequences of the procedure.
• Some instances , may not directly lead to coronary revasc
leading to the use of non invasive work up.
• Stress testing is commonly used for both diagnosis and risk
strati
fi
cation of patients with coronary artery disease.

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Radiation exposure

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2013 Appropriate Utilization of Cardiovascular Imaging A Methodology
for the Development of Joint Criteria for the Appropriate Utilization of
Cardiovascular Imaging by the American College of Cardiology
Foundation and American College of Radiology

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As de
fi
ned by the “2013 ACC/AHA/AATS/PCNA/SCAI/ STS Focused Update of the Guideline for the
Diagnosis and Management of Patients with Stable Ischemic Heart Disease”
Pretest Probability
• Low pretest probability indicates <10% probability of disease
prior to the test under consideration.
• Moderate pretest probability is a range of 10% to 90% pretest
probability.
• High pretest probability is a >90% likelihood of the presence of
the disease entity under question prior to any testing.

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Stress Testing and Risk of Findings on Noninvasive Testing
• Criteria de
fi
ned for traditional exercise stress tests::
• Low-risk stress test
fi
ndings: associated with a cardiac mortality
of less than 1% per year
• Intermediate-risk stress test
fi
ndings: associated with a 1% to
3% per year cardiac mortality
• High-risk stress test
fi
ndings: associated with a greater than 3%
per year cardiac mortality

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Non invasive risk stratification

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Tracers used in nuclear stress test
• The most commonly used radioisotope for SPECT imaging is
99m-technetium labeled perfusion agents such as 99m-Tc-
sestamibi, 99m-Tc-tetrofosmin.
• Use of thallium-201 is becoming increasingly less common as
Tc99 has higher energy, less attenuation, and less scatter of
photons.

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Position of scanning
• Supine position is routinely used for SPECT imaging.
• Prone imaging has been reported to produce less patient motion
and less inferior wall attenuation than supine imaging.
• By comparing supine and prone images, artifacts will resolve or
change their location whereas true perfusion defects will remain.

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Delay Time for Imaging
• Allow clearance of subdiaphragmatic activity, and allow patient
to recover fully from exercise, thus returning heart rate to
baseline (reducing gating artifact), avoiding “upward creep” from
changes in respiratory patterns while dyspnea resolves and to
minimize interference from hepatic uptake.
• With 201-Tl, imaging should begin approximately 10 to 15
minutes after stress testing.
• Care should be taken to avoid repeat imaging with 201Tl, as
signi
fi
cant 201-Tl redistribution occurs as early as 20 minutes
after
fl
ow restoration, which may reduce the extent and/or
severity of true defect(s).

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• 99mTc sestamibi and 99mTc tetrofosmin, due to lack of
redistribution or washout, allow delayed imaging and, therefore,
permit stress testing and tracer injection to take place at a
location remote from the imaging laboratory
• The standard delay between injection of 99mTc sestamibi or
tetrofosmin and scan is 30 to 60 minutes for rest and 15 to 60
minutes for stress.

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• One-day rest/stress (or stress/rest) study: Radiopharmaceutical
agent used for the second injection is 3x
fi
rst dose.
• Images acquisition is performed 15 to 60 minutes after the
injection, or it can be delayed up to 2 hours depending on type
stress – exercise vs. pharmacological.
• Radiation exposure can be reduced substantially by using a
weight-based radiopharmaceutical agent.

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• Two-day Tc99m- based protocol: radiopharmaceutical agent is
used at the same dosage for rest and stress images.
• This protocol is more useful in larger patients since low-dose
tracer may make image acquisition di
ffi
cult.
• But it is di
ffi
cult for patients to perform this entire stress/rest in 2
days.

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Exercise or pharmacological
• In patients who can exercise, it is the preferred form of stress to
achieve cardiac workload.
• The radioactive tracer is injected near the peak of physical
activity, and it should be continued for at least a minute of
exercise to allow the radioactive tracer to distribute.

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• Those who are unable to exercise, pharmacological agents are
used,
• there are two types, vasodilator or inotropic/chronotropic drugs.
• Vasodilators are adenosine, dipyridamole, and regadenoson, -
causing coronary vasodilation and increase coronary blood
fl
ow
during stress, which is 3 to 5 times the resting blood
fl
ow. The
fl
ow through the normal coronary arteries increases up to
fourfold during coronary vasodilation and radiotracer uptake.
• The presence of
fl
ow-limiting stenosis in the coronary artery
causes a relative reduction in blood
fl
ow during stress leading to
reduced radiotracer uptake, re
fl
ecting as a perfusion defect.

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• Adenosine acts via the A2A receptor on coronary arteries. —
administered via infusion pump at the dose of 140 mcg/kg/minute,
over 4-6 minutes, then radionuclide is injected over 10 seconds, and
adenosine infusion is continued for additional 3 minutes.
• Dipyridamole blocks the cellular uptake of adenosine. Its half-life is 30
to 35 minutes — administered via an infusion pump at the dose of 140
mcg/kg per minute for 4 minutes with a maximum dose of 0.56 mg/kg.
The radionuclide is administered after 3 to 5 minutes after the infusion.
• Aminophylline is often used as a reversal agent to reduce side e
ff
ects.
• Simultaneous low-level exercise improves image quality, allows us to
assess exercise capacity, and risk-stratify future cardiac events.

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• Regadenoson is a selective A2A receptor blocker on vascular
smooth muscles + also on the A1 receptor on atrioventricular
node and A2B, A3, A4 responsible for common side e
ff
ects such
as AV block and bronchospasm, respectively.
• Regadenoson has a rapid onset of 30 seconds and lasts about 2
to 5 minutes
• It is administered at a dose of 400 mcg in a pre
fi
lled single-dose
syringe over 10 seconds, followed immediately by 5 ml saline
fl
ush.
• The radionuclide is administered after the saline
fl
ush.

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• Inotropic/chronotropic agent::
• Dobutamine - administered over graded format starting at 5
mcg/kg and gradually increasing it to 10, 20, 30, and 40 mcg/kg/
minute at every 3-minute interval.
• The standard end-point of dobutamine rMPI is to achieve a heart
rate of at least 85 percent of the age-predicted maximum heart
rate. Atropine at a dose of 0.5 mg at each time to a total dose of
2 mg can be administered as needed to achieve the desired
heart rate. The procedure should be terminated if there is any
signi
fi
cant arrhythmia, hypotension <90 mmHg, or severe
hypertension

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Interpretation

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• 1) evaluation of the raw images or the reconstructed maximum intensity
projection image (MPI, for CZT scanners) in cine mode, and a review of
the sinogram and linogram images, to determine the presence of potential
sources of image artifact and the distribution of extracardiac tracer activity
• (2) interpretation of images with respect to the location, size, severity, and
reversibility of perfusion defects, as well as cardiac chamber sizes, and
the presence or absence of increased pulmonary uptake
(especially 201Tl);
• (3) evaluation of the results of quantitative perfusion analysis;
• (4) evaluation of functional data obtained from the gated images;
• (5) consideration of clinical data, stress ECG and hemodynamic data that
may in
fl
uence the
fi
nal interpretation of the study.

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Conventional slice display of SPECT images
• Three sets of tomographic images should be displayed:
• (1) short-axis - slices perpendicular to the long axis of the LV,
with the apical slices to the left and the base at the right.
• (2) vertical long-axis - slices parallel to the septum, with septal
slices on the left and the lateral slices on the right.
• (3) horizontal long-axis - slices parallel to the inferior wall, with
inferior slices on the left and anterior slices on the right.

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• the sequential images should be displayed aligned and adjacent
to each other, with stress followed by rest perfusion, either in
rows or columns.

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Initial Image Analysis and
Interpretation

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Ventricular dilation
• note whether there is LV enlargement at rest or post-stress
• Dilation of the LV on both the stress and resting studies usually
indicates LV systolic dysfunction
• An increased stress-to-rest LV cavity ratio, transient ischemic
dilation (TID), also referred to as transient cavity dilatation (TCD),
has been described as a marker for high-risk coronary disease.
• Transient ischemic dilatation about 30 minutes after completion
of stress testing, is more likely to represent apparent dilatation of
the ventricle from di
ff
use subendocardial ischemia, or
microvascular disease in the absence of epicardial coronary
disease.

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Lung uptake
• The presence of increased lung uptake after 201-Tl perfusion
imaging has been described as an indicator of poor prognosis.
• No clear consensus has emerged with 99mTc, although
increased lung uptake suggest resting LV systolic dysfunction in
patients who are not candidates for gated-SPECT imaging due to
severe arrhythmias.

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Right ventricular uptake
• Right ventricular uptake may be qualitatively assessed on the raw
projection data and on the reconstructed data.
• RV uptake increases in the presence of RV hypertrophy, most
typically because of pulmonary hypertension.
• In globally reduced LV due to relative increase.
• Regional abnormalities of RV uptake may be a sign of ischemia or
infarction in the distribution of the right coronary artery.
• The size of the RV should be noted qualitatively, RV dilation
indicate presence of right heart volume overload due to conditions,
such as atrial septal defect or severe tricuspid regurgitation.

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Perfusion defect location
• The location of the perfusion defects is characterized using the
17-segment heart model or as using speci
fi
c myocardial walls
(apical, anterior, inferior, and lateral).
• Segments are roughly assigned to coronary arterial territories.

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• An inferior defect may represent disease in either the right
coronary artery or the left circum
fl
ex coronary artery territory.
• However, an inferior defect extending into the basal inferoseptum
more likely represents posterior descending CAD, while an
inferior defect extending in to the inferolateral segments
represents posterolateral CAD.
• An anterolateral defect extending into the anterior wall may
represent diagonal CAD, while anterolateral defect extending into
the inferolateral wall may represent obtuse marginal CAD.

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Perfusion defect severity and extent
• Expressed qualitatively as mild, moderate, or severe.
• Extent is described as small, medium, or large,
• Defects whose severity and extent do not change between
stress-and-rest images are categorized as “
fi
xed” or
“nonreversible.”
• When perfusion defects are more severe and/or extensive on
stress compared to rest images, a qualitative description of the
degree of reversibility is required.

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• Provides an important index that is applicable to diagnostic and
prognostic assessments and to guide therapy.
• Defect severity is scored using a 0 to 4 score

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• Defect severity can also be expressed as
• mild (10% to < 25% reduction in counts),
• moderate (25% to < 50% reduction in counts),
• severe (≥50% reduction in counts), or absent tracer uptake
(background counts).
• Defect extent may be described as
• small (involving 1 to 2 segments), involve < 10%,
• medium (involving 3 to 4 segments), involve 10% to 20%,
• large (involving ≥ 5 segments); involve ≥ 20% of the LV

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• It is recommended that summed scores and percent myocardium
metrics be calculated.
• For a 17-segment model with a 0 to 4 scoring scheme, the
maximal possible score is 68, and percent myocardium
abnormal, ischemic or scarred is calculated as the following:
(summed score × 100/68)

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• Quantitative analysis of static perfusion images is useful to supplement
visual interpretation.
• This quantitative analysis is typically displayed as a “bullseye” or polar
plot.
• Most techniques of quantitative analysis are based on radial plots of
short-axis slices and analyze the apex separately. These plots are then
normalized to allow comparison to a normal gender-speci
fi
c and camera-
speci
fi
c database.
• Defect severity may be quantitatively expressed as the number of
standard deviations by which the segment varies from the normal range
for that particular segment.

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Reversibility
• Reversibility of perfusion defects may be categorized qualitatively as
partial or complete
• Complete reversibility :: when the activity in the defect returns to a level
comparable to surrounding normal myocardium.
• The semiquantitative scoring system may be used to de
fi
ne reversibility
as a greater than or equal to 2-grade improvement or improvement to a
score of 1
• Reversibility (
fi
xed = no reversibility; mildly reversible; moderately
reversible; predominantly reversible; predominantly
fi
xed)

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Gated Myocardial Perfusion SPECT
• A systematic approach to the display and interpretation of the
ventricular function derived from gated SPECT is important.
• Gated SPECT display - to asses regional wall motion and systolic
wall thickening
• Wall motion and wall thickening are generally concordant. With
exception in left bundle branch block, post pericardiotomy, RV
pacing, or after cardiac surgery where septal wall motion is
frequently abnormal (paradoxical), but there is normal wall
thickening
• Left ventricular ejection fraction and volumes. - categorized as
normal (> 55% to < 70%), low normal (50% to 55%), mildly (45% to
< 50%), moderately (35% to < 45%), severely reduced (< 35%).

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• Fixed perfusion defects that do not show a corresponding
abnormality of wall motion are more likely due to artifacts.
• unless post-stress stunning is present, in majority cases post-
stress regional wall motion is normal with stress-induced
ischemia, Because the post-stress gated images are acquired
more than 30 minutes after exercise or pharmacologic stress, by
that time stress-induced regional dysfunction will have resolved

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Viability
• Myocardial viability can be determined using SPECT (99mTc
and 201Tl), PET radiotracers (18F-FDG), or low-dose dobutamine
imaging (presence of inotropic contractile reserve), or late
gadolinium enhancement cardiac magnetic resonance imaging
(presence of scar).
• Myocardial uptake and retention of 99mTc and 201-Tl tracers
indicate integrity of myocyte cell walls and mitochondrial function
(99mTc), indicating viability, while 18F-FDG uptake re
fl
ects
myocardial glucose metabolic activity.

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• Typical SPECT imaging protocols include rest 99mTc or 201-Tl
perfusion imaging, with added redistribution imaging at 4 and/or
24 hours with 201-TI [with severely reduced tracer uptake on
rest images indicates viability]
• evaluation of stress perfusion (ischemia implies viability), nitrate
enhanced perfusion {Hypoperfused myocardial segments with
unequivocal improvement following}, inotropic contractile reserve
with changes in regional/global function with low-dose
dobutamine are important adjuncts to enhance the detection of
myocardial viability.

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• Myocardial segments with % peak radiotracer activity on normalized polar
plots less than or equal to 50% are considered nonviable and greater than
50% are considered viable.
• The extent of viability (greater than 10% hibernating myocardium) is an
important determinant of recovery of LV function following coronary
revascularization
• myocardial segments with normal perfusion or mild hypoperfusion (score 0
or 1) are viable; moderately hypoperfused segments (scores of 2) represent
a combination of viable and nonviable myocardium; and severely
hypoperfused segments (scores of ≥3) represent nonviable myocardium

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• if critical amounts of subendocardium are infarcted, even if
perfusion is relatively preserved, regional function may not
improve post revascularization. {slightly higher sensitivity of
techniques based on perfusion and higher speci
fi
city of
techniques based on contractile reserve assessment to predict
recovery of LV function}

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• Viability imaging is indicated in heart failure and CAD, as well as
before revascularization in heart failure patients with CAD (Class
IIa)

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Artefacts

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Motion artefacts
• The raw planar images should be reviewed in a rotating format
• - a cine display of the planar projection data is highly
recommended because motion in both the vertical (craniocaudal)
and horizontal (side-to-side) axes are readily detectable.
• - a static sonogram or linogram may be used to detect patient
motion.
• Vertical (y-plane) motion is more readily detected on the linogram
• Horizontal (x-plane) motion, often overlooked on the rotating cine
images, is easily observed on the sinogram

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• Generally, vertical (i.e., craniocaudal) motion has less of an e
ff
ect
on the accuracy of the study than horizontal (side-to-side)
motion, especially when the heart returns to the same baseline.
• Vertical motion is also much easier to correct manually or with
semi-automated software.

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Attenuation artifacts and attenuation correction
• sources of attenuation, the most common being the diaphragm
in men and the breast in women.
• Breast attenuation artifact is most problematic when the left
breast position varies between the rest-and-stress images (i.e.,
‘shifting breast attenuation artifact’).
• artifact can be con
fi
rmed by repeating the acquisition with the
left breast repositioned.

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Reconstruction artefacts
• Intense extracardiac tracer activity in close proximity may create
artifactually increased uptake in adjacent myocardium that could
mask a perfusion defect or be misinterpreted as reduced uptake in
remote myocardial segments due to image normalization to the
artifactually “hot” area.
• It is generally increased following pharmacologic stress (due to
splanchnic hyperemia); and reduced following adequate exercise
stress with greater than 85% maximum predicted heart rate (due to
hyperemia to the exercising muscles).
• These artifacts can often be eliminated by repeating the acquisition
after the activity level in the adjacent extracardiac structure has
decreased. Some methods to decrease extracardiac activity include
delayed imaging, food, water, or milk intake, and prone imaging.

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Myocardial count statistics
• Factors involved in the
fi
nal count density of perfusion images,
includes ::
• body habitus, exercise level achieved, administered radiotracer
activity, acquisition time, energy window, and collimation.
• Apparent perfusion defects can be artifactually created simply
because of low-image count density.
• Greater than 1,000,000 counts/LV are shown to be adequate for
novel CZT detector cameras.

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Dextrocardia
• There are a few studies in literature that have reported MPI
studies in dextrocardia.
• The term “mirror-image dextrocardia” is used in cases of
dextrocardia with normal vascular anatomy, accompanied with
situs inversus.
• In such cases, the anterior and inferior walls of the heart remain
the same, whereas the septal and lateral walls change position in
the right-left direction.

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the projection image was acquired while the feet-first prone position was
selected during analysis and the head-first supine position during imaging

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Final Interpretation of MPI with Clinical and Stress-Test
Data
• After a systematic image interpretation as discussed previously,
perfusion images are reported in categories of normal, probably
normal, equivocal, probably abnormal or abnormal.
• ASNC recommends a de
fi
nitive reporting of the scan as normal
or abnormal and minimizing use of probably normal or probably
abnormal

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• To avoid reader bias, the initial interpretation of the perfusion
study should ideally be performed without any clinical
information other than the patient’s gender, height, and weight

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Stress First /stress only - approach
• Stress-only imaging signi
fi
cantly reduces patient radiation
exposure (25% to 80%. Around 1mSv), improves patient
convenience, and results in lower cost by eliminating the second
radiotracer administration and scan.
• signi
fi
cantly reduces radiation exposure to nuclear medicine
technologists and nursing sta
ff
working in nuclear cardiology
laboratories (~40% to 50%),

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• A recent randomized study also showed that incorporation of a
stress-only imaging algorithm in low- to intermediate-risk
patients with acute chest pain was comparable to CT coronary
angiography for predicting patient outcome with similar time to
diagnosis, hospital stay and hospital costs

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Winchester D, Je
ff
rey R, Wymer D, et al. Simpli
fi
ed approach to stress-
fi
rst nuclear myocardial perfusion imaging: implementation of
Choosing Wisely recommendations. BMJ Open Quality
2019;8:e000352. doi:10.1136/ bmjoq-2018-000352
• The stress-
fi
rst protocol was to inject 0.4 mg of regadenoson
followed by 9–13 millicuries (mCi) of Tc-99m*-tetrofosmin.
• CT attenuation correction was used for all studies and prone
imaging was acquired when feasible.
• After acquisition, studies were reviewed by a physician who
determined if the study was normal or if rest imaging was
required. If necessary, rest injection/acquisition was performed
30min after stress imaging with 37–45 mCi of radiotracer.

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Winchester D, Je
ff
rey R, Wymer D, et al. Simpli
fi
ed approach to stress-
fi
rst nuclear myocardial perfusion imaging: implementation of
Choosing Wisely recommendations. BMJ Open Quality
2019;8:e000352. doi:10.1136/ bmjoq-2018-000352
• In panel A, the median estimated e
ff
ective doses for the control and
stress
fi
rst cohorts are compared.
• In panel B, the proportion of myocardial perfusion imaging (MPI) tests
considered normal and abnormal for the two cohorts are compared.

70. DR VANDNA
Winchester D, Je
ff
rey R, Wymer D, et al. Simpli
fi
ed approach to stress-
fi
rst nuclear myocardial perfusion imaging: implementation of
Choosing Wisely recommendations. BMJ Open Quality 2019;8:e000352. doi:10.1136/ bmjoq-2018-000352
• project suggests that abnormal MPI, coronary angiography and
PCI rates are similar for stress-
fi
rst imaging and rest- stress
imaging even in an unselected population
• improved safety through reduced radiation dose and reduced
time for the patient being scanned.

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Personalizing stress protocols

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Combining CT Calcium Score with MPI
• The ACCF/AHA Practice Guidelines for Assessment of
Cardiovascular Risk rate CT coronary artery calcium scoring
(CACS) as Class IIa for asymptomatic adults at intermediate risk
(10% to 20% 10-year risk) and Class IIb for individuals at low to
intermediate risk (6% to 10% 10-year risk).
• Many patients referred for MPI meet the Practice Guideline
criteria for CACS.
• In patients with a normal stress MPI, the CACS may identify
those with calci
fi
ed atherosclerosis who would likely bene
fi
t from
aggressive risk factor modi
fi
cation.

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• normal stress-
fi
rst MPI study may be accompanied by worrisome
exercise treadmill test
fi
ndings suggestive of ischemia. In such
cases, a rest MPI is still not indicated; however, further evaluation
with CT angiography (for ischemic ECG changes) or invasive
angiography (for high-risk stress-test
fi
ndings such as ST
elevation, exercise induced hypotension, ventricular tachycardia)
may be warranted. CT angiography may also be considered for
excluding signi
fi
cant CAD in patients with a normal stress-only
study but who have ongoing chest pain symptoms of unclear
cardiac etiology.