Stress imaging and viability assessment

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Stress Imaging and Viability
Assessment

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Debates about the issue
1-Which modality to choose?
2-Pharmacological Vs exercise?
3-Inotropic Vs vasodilator stressor?
4-Diagnostic accuracy and prognostic value of each
modality.
5-Early Post MI ischemia and Viability Assessment.

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Debates about the issue:
modality.

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Indications for the use of pharmacological
imaging modalities:
1. Inadequate exercise secondary to neurological,
orthopedic, peripheral vascular or respiratory problems.
2.Poor image degradation with exercise.
3.Poor patient motivation to exercise

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Debates about the issue
modality.

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 The choice of one pharmacological test over the
other as the preferred imaging modality may
depend upon local drug cost, tests safety, and
expertise available.
 Vasodilator, inotropic, and exercise stresses are all
needed to optimize the enormous diagnostic and
prognostic potential of stress testing.
 Whatever the test choice, the results of
physical(more physiological) or pharmacological
stress echo should be used as a “gatekeeper” to
coronary angiography.

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 The use of stress echocardiography is advocated in
the ESC guidelines on suspected ACS (class I, level
A evidence) and is categorized as appropriate in
suspected ACS in North American guidelines.
 In both guidelines , the use of stress
echocardiography is mainly recommended for
patients with no resting chest pain, normal ECG
findings, negative troponin, and a low risk score.

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In Europe, both the law and the referral guidelines for
medical imaging recommend a justified, optimized, and
responsible use of testing with ionizing radiation .
1-The justification principle : “if an exposure cannot be
justified, it should be prohibited”.
2- According to ALARA principle, “all doses due to medical
exposures must be kept (As Low As Reasonably
Achievable”), and the responsibility principle.

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Prognostic value:
 SE has been shown to play an important role in
the prediction of mortality and composite cardiac
events in patients with known or suspected CAD.
 A normal exercise SE is associated with a
mortality of <1%/year, while normal
pharmacological stress has been associated with
mortality <1.5% (patients undergoing
pharmacological stress have more comorbidities
and, hence, a greater cardiovascular disease
burden).

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Cost-effectiveness of functional cardiac testing in the diagnosis and
management of coronary artery disease: a randomized controlled trial. The
CECaT trial.
Sharples L1, Hughes V, Crean A, Dyer M, Buxton M, Goldsmith K, Stone D.
RESULTS:
The 898 patients were randomized to angiography (n = 222), SPECT (n = 224), MRI (n = 226) or stress echo (n =
226). Initial diagnostic tests were completed successfully with unequivocal results for 98% of angiography, 94% of
SPECT (p = 0.05), 78% of MRI (p < 0.001) and 90% of stress echocardiography patients (p < 0.001). Some 22%
of SPECT patients, 20% of MRI patients and 25% of stress echo patients were not subsequently referred for an
angiogram. Positive functional tests were confirmed by positive angiography in 83% of SPECT patients, 89% of
MRI patients and 84% of stress echo patients. Negative functional tests were followed by positive angiograms in
31% of SPECT patients, 52% of MRI patients and 48% of stress echo patients tested.
CONCLUSIONS:
Between 20 and 25% of patients can avoid invasive testing using functional testing as a gateway to angiography,
without substantial effects on outcomes. The SPECT strategy was as useful as angiography in identifying
patients who should undergo revascularization and the additional cost was not significant, in fact it would be
reduced further by restricting the rest test to patients who have a positive stress test. MRI had the largest
number of test failures and, in this study, had the least practical use in screening patients with suspected CAD,
although it had similar outcomes to stress echo and is still an evolving technology. Stress echo patients had a
10% test failure rate, significantly shorter total exercise time and time to angina at 6 months post-treatment, and
a greater number of adverse events, leading to significantly higher costs. Given the level of skill required for
stress echo, it may be best to reserve this test for those who have a contraindication to SPECT and are unable
or unwilling to have MRI

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Conclusion:
Recent European Society of Cardiology guidelines clearly
state that stress echocardiography provides similar
diagnostic and prognostic accuracy as radionuclide stress
perfusion imaging, but at a substantially lower cost, without
environmental impact, and with no biohazards for the
patient and the physician.
Different stresses (exercise, dipyridamole, dobutamine)
have comparable diagnostic and prognostic accuracy
according to evidence-based medicine mirrored in
European guidelines.

Stress Nuclear
(SPECT and PET)
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Single-Photon Emission Computed Tomography (SPECT) Fleishmann et al
(1998), meta-analysis of 44 articles using Tl 201 or Tc 99m sestamibi
demonstrated that both exercise echocardiography and exercise SPECT
had similar sensitivities; 85% vs. 87%, respectively but with lower
specificity compared to echocardiography; 64 vs. 77%.
This result is in agreement with Kim et al (2001) ,meta-analysis, in which
using dobutamine with SPECT and ECHO showed similar sensitivities,
82% and 80%, respectively.
A meta-analysis by Imran et al, showed that stress SPECT(using exercise
in three studies, dobutamine in one study and dipyridamole in 6 studies)
had higher sensitivity (88% vs. 70%) and lower specificity (67% vs. 90%)
compared to ECHO.

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Head-to-head comparison of dipyridamole echocardiography
and stress perfusion scintigraphy for the detection of
coronary artery disease: a meta-analysis. Comparison between
stress echo and scintigraphy.
METHODS: We performed a meta-analysis of peer reviewed articles, published
in English language reporting head-to-head comparison of DET vs. SPS for the
diagnosis of CAD. Data of 10 studies comprising 651 patients from 10 different
institutions were analyzed. DET dose was 0.56 mg/kg (low dose) in two studies,
0.75 mg/kg in 10 min or 0.84 mg/kg in 10 min (high dose) in six studies, and 0.84
mg/kg in 6 min (accelerated high dose) in one study and 0.84 mg/kg in 10 min + 1
mg atropine co-administration (augmented dose) in one study. SPS was
performed with dipyridamole in six studies, with exercise n three studies and with
dobutamine in one study.
RESULTS: The overall diagnostic accuracy of the two tests was almost similar,
77% (95% CI = 74-81) for DET vs. 81% (95% CI = 78-84) for SPS (p = ns). SPS
gave higher sensitivity, 88% (95% CI = 85-89) than DET, 70% (95% CI = 66-75) in
cumulative data (p < 0.0001) while DET gave higher specificity, 90% (95% CI =
86-94) vs. 67% (95% CI = 60-73) (p < 0.0001). With state-of-the-art protocols, i.e.
accelerated dose and atropine augmented high dose, sensitivity of DET improved
and overall accuracy was better than SPS (p < 0.05).
CONCLUSION: DET and SPS have a similar diagnostic accuracy. DET has a
markedly higher specificity regardless of the dose employed. SPS shows a
superior sensitivity, however this sensitivity gap diminishes when more
aggressive dipyridamole dosage is used for the stress echocardiography.

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TI-201 is one of the longest used agents in MPI and has
been found to be effective in the detection of CAD with
an estimated sensitivity and specificity of 89% and 76%
respectively .
The limitations seen with the use of TI-201 include long
half life, poor count statistics, and low-energy emission.
Because of the higher radiation exposure when
compared to alternative agents, the use of thallium has
been discouraged unless there are no other options.

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An alternate option is Tc-99m, which is associated with
improved imaging quality secondary to higher photon
energy and the ability to administer higher doses
because of a shorter half-life 6 hours when compared to
thallium 72 hours.
In studies directly comparing SPECT using Tl-201 and
Tc-99m sestamibi, the sensitivity of Tc-99m sestamibi
was significantly greater that that for Tl-201 (93% versus
80%), although the specificity was similar for the two
agents.

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 In the more recent ROBUST study of 2560
individuals randomized to undergo SPECT perfusion
imaging with either Tl-201, Tc-99m sestamibi, or Tc-
99m tetrofosmin, the sensitivities and specificities of
the three agents were similar in the subset of 137 who
underwent subsequent angiography.
 However, image quality was superior for the studies
acquired with the Tc-99m-based agents, most likely
due in part to the lower energy of Tl-201.

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In conclusion: There are technical differences between the tracers.
Overall image quality score is superior using technetium, with less
low-count artefact and less attenuation.
Stress defect depth and extent are slightly greater using thallium,
with no difference between MIBI and tetrofosmin.
All three tracers perform well in clinical terms, with high sensitivity
and specificity for angiographic stenosis and no differences in
accuracy between the tracers.

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Prognostic Value of SPECT MPI:
Observational study of 1,187 consecutive patients showed
excellent 1-year outcome in patients with normal MPS
compared with those with abnormal MPS (0% MI/death versus
11% MI and 8% cardiac death, P < 0.001).

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Comprehensive strategy for the evaluation and triage of the chest
pain patient.
Tatum JL1, Jesse RL, Kontos MC, Nicholson CS, Schmidt KL, Roberts CS, Ornato JP.
METHODS: We conducted an observational study of 1,187 consecutive patients seen in the
ED of an urban tertiary care hospital with the chief complaint of chest pain. Within 60
minutes of presentation, each patient was assigned to one of five levels on the basis of his
or her risk of myocardial infarction (MI) or unstable angina (UA): level 1, MI; level 2, MI/UA;
level 3, probable UA; level 4, possible UA; and level 5, noncardiac chest pain. In the lower
risk levels (3 and 4), immediate resting myocardial perfusion imaging was used as a risk-
stratification tool alone (level 4) or in combination with serial markers (level 3).
RESULTS: Acute MI, early revascularization indicative of acute coronary syndrome, or both were
consistent with risk designations: level 1: 96% MI, 56% revascularization; level 2: 13% MI, 29%
revascularization; level 3: 3% MI, 17% revascularization; level 4: .7% MI; 2.5% revascularization.
Sensitivity of immediate resting myocardial perfusion imaging for MI was 100% (95% confidence interval
[CI], 64% to 100%) and specificity 78% (74% to 82%). In patients with abnormal imaging findings, risk for
MI (7% versus 0%, P < .001; relative risk [RR], 50; 95% CI, 2.8 to 889) and for MI or revascularization
(32% vs 2%, P < .001; RR, 15.5; 95% CI, 6.4 to 36) were significantly higher than in patients with normal
imaging findings. During 1-year follow-up, patients with normal imaging findings (n = 338) had an event
rate of 3% (revascularization) with no MI or death (combined events: negative predictive value, 97%; 95%
CI, 95% to 98%). Patients with abnormal imaging findings (n = 100) had a 42% event rate (combined
events: RR, 14.2; 95% CI, 6.5 to 30; P < .001), with 11% experiencing MI and 8% cardiac death.
CONCLUSION: This strategy is a safe, effective method for rapid triage of chest pain patients. Rapid
perfusion imaging plays a key role in the risk stratification of low-risk patients, allowing discrimination of
unsuspected high-risk patients who require prompt admission and possible intervention from those who
are truly at low risk.

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A growing consensus endorses PET as the most
effective imaging technique for myocardial perfusion
imaging and points to some very clear advantages
compared with SPECT.
PET imparts a higher specificity than SPECT, which is
most likely a consequence of its superior attenuation
correction, increased count-density images, and superior
spatial resolution.
PET has improved spatial resolution as 2–3 mm as
compared with the 6- to 8-mm resolution of conventional
SPECT imaging

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Despite this, cardiac Positron Emission Tomography (PET)
perfusion imaging has been recognized as superior to
standard SPECT imaging due to higher image quality and
a greater efficiency .
However, it has been infrequently used due to limited
availability of camera systems, radiopharmaceuticals and
technical difficulties in cardiac acquisition and processing.

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Recently, the number of PET Camera systems has
increased substantially and acquisition, processing and
display of Cardiac PET studies has vastly improved.
Thus, since its introduction in the early 1980s , the use
of Cardiac PET perfusion imaging has greatly increased
within the last 8 years
Its superior sensitivity and specificity over SPECT
myocardial perfusion imaging , as well as the routine
availability of Rubidium-82 (Rb-82), has made cardiac
PET an important tool in the detection and risk strati fi
cation of coronary artery disease.

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Several studies have demonstrated that PET offers a
superior diagnostic accuracy in detecting CAD.
A recent systematic review of PET by Al Moudi et al. ,
demonstrated a superior sensitivity and specificity of PET
when compared to SPECT leading to increased
diagnostic accuracy.

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Diagnostic accuracy of PET over SPECT in different coronary vessel
lesions

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Cardiac PET imaging acquisition protocols are much
more efficient than SPECT.
Most cardiac PET perfusion laboratory protocols can be
completed in 25–40 min. This is a greater than 50%
reduction in procedure time when compared to SPECT.

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Obese patients suspected of having coronary artery
disease may also benefit from a Cardiac PET perfusion
study for diagnosis or risk stratification.
Patients weighing over 250 lb, with a BMI greater than 30
should be considered for cardiac PET rather than
SPECT.
Cardiac PET isotopes generate a 3-fold higher energy
emission than SPECT can capture and therefore offer
better diagnostic accuracy without the attenuation artifact
that is often seen with SPECT in this patient population.
In addition, PET has a much more robust attenuation
correction protocol making it more reliable in this patient
population.

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One of the important qualities of cardiac PET is its
higher accuracy in detecting multivessel disease. When
contrasted to SPECT for the detection of multivessel
disease, the sensitivity is 71% for PET as compared to
48% for SPECT.
For this reason, cardiac PET may be a better option for
not only identifying territories that would benefit from
revascularization, but also for risk stratifying patients that
may have multivessel coronary artery disease.

Safety and radiation exposure
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Both SPECT and PET will, albeit low, expose the patient to radiation.
However by following simple protocols this exposure can be minimized.
SPECT, tracer and protocol choice can substantially reduce the radiation
expose. Thallium results in 15–20 mSv of exposure while Technetium
results in 8–10.
In contrast, cardiac PET can reduce the exposure to as low as 3–5 mSv
primarily due to the more efficient protocol and better suited isotope.
These data demonstrate PET perfusion imaging has favorably radiation
dosimetry and should be considered for the appropriate patient.

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CMR is primarily a functional test; however it can identify
the anatomy of coronary arteries. Detection of myocardial
ischemia is mainly achieved by 2 main techniques;
assessment of wall motion abnormalities mainly with
dobutamine and assessment of myocardial perfusion
during vasodilators (adenosine and dipyridamole)
infusion.
Contrast agent “gadolinium- based contrast agents” or
(GBCAs) is used for this purpose. CMR is mainly
indicated for patients with intermediate pre-test likelihood
of CAD who do not have the ability to exercise.

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Stress Perfusion Imaging
MRI perfusion studies use the “first pass” of an
intravenously injected Gd contrast agent during
administration of a vasodilator (i.e. adenosine or
dipyridamole) to depict hemodynamically significant
coronary artery stenosis .

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Overall, the literature over the last 3 years supports the diagnostic superiority of
stress CMRI and PET over the alternatives.
However, these comparative studies look directly at myocardial perfusion
imaging.
This ignores the fact that stress CMRI is a comprehensive study, including gold
standard for quantitative functional analysis and high-resolution scar imaging
for viability assessment in segments with fixed perfusion defects.
In addition, rapid technological improvement in the field has improved the
speed, quality, and reliability of MR stress perfusion imaging.

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 Edema Imaging
 T2-relaxation time is linearly correlated to the
percentage of free water, and edema is visible on T2-
weighted MR sequences in infarcted myocardium as
bright areas (hyper-intense).
 In acute MI patients, it is accepted that the bright
myocardium on T2-weighted imaging reflects the
myocardium at risk.

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The emergence of delayed enhancement imaging for
viability assessment represented a landmark in the
evolution of assessing myocardial viability and has since
spurred growing acceptance of CMRI as a valuable tool
for evaluation of IHD.
CMRI plays a valuable role In ischemic cardiomyopathy,
both suspected and confirmed CAD, and suspected MI.

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It has become the gold standard for quantification of
both right and left ventricular volumes and function and,
as the data above demonstrate, is a powerful tool for
viability evaluation prior to revascularization.
In addition, early data promises improved risk
stratification for defibrillator placement. Perhaps most
importantly, CMRI stands to reduce unnecessary
intervention, both by predicting functional recovery and
by proposing alternative diagnoses unrelated to IHD.

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CT perfusion imaging is a new promising
technology that aims to enhance the role of CTA in
practice by allowing it to detect coronary stenoses
and its functional significance in single test.
Moreover, a prospective multi-center international
trial (CORE 320)showed that combining CTA and
CT perfusion had a strong diagnostic accuracy in
determining flow-limiting coronary stenoses as
compared to ICA and SPECT-MPI

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A meta-analysis by Tashakkor et al
(2012) showed that CT perfusion
combined to CTCA had a sensitivity of
81%, specificity of 93%, PPV 87% and
NPV 88%.

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Debates about the issue:
modality.

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Pooled data from viability studies that compare
different modalities .

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Conclusion:
The assessment of myocardial viability has become an
integrated part of the diagnostic and prognostic work-up of
patients with heart failure symptoms attributable to ischemic
cardiomyopathy.
The current analysis of pooled data showed that sensitivity for
prediction of functional recovery after revascularization is high
for all techniques reviewed here. Specificity is highest for
LDDE and lowest for Tl-201 stress– redistribution–reinjection
and Tl-201 rest–redistribution. Thus, the available evidence
favors the use of LDDE as the technique of first choice for
prediction of regional functional recovery in patients with
chronic ischemic LV dysfunction for whom revascularization is
contemplated

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