2014 Myocardial Perfusion Imaging - Prof Libhaber 28-9-2017

Myocardial Perfusion Imaging:
How does it affect clinical

decisions?
Prof. Carlos D. Libhaber
Wits University
Johannesburg – South Africa
During the past decades, the most rapidly
growing areas of nuclear cardiology have
been in the application of stress
myocardial perfusion SPECT (MPI) and
lately stress myocardial perfusion PET
for prognostication in patients with known
or suspected CAD.
This growth has been stimulated by a
wealth of studies in large patient groups,
as well as a basic shift in the clinical
approach to patient management toward
strategies based on patient risk rather
than coronary anatomy as an endpoint.
The angina cascade
Myocardial oxygen demand
Angina
Ischemic ST depression
Global LV dysfunction
Significant perfusion defect
Regional myocardial dysfunction

Flow heterogeneity
Rest
Exercise treadmill time

Beller GA et al, Am J Cardiol 61; 1988
Symptomatic
Role of Exercise ECG
Meta-analysis: 19 exercise ECG studies,

3721 women, 1977 men
Gibbons RJ et al, Circulation 2002;106:1883-1892

Symptomatic
Role of Cardiac Radionuclide
4 Imaging
Santana-Boado C et al, J Nucl Med 1998;39:751-755

Risk-based approach to patient
care
A new paradigm in patient management is

that of a risk-based approach to patients
with suspected CAD without limiting
symptoms.
Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

care
With a risk-based approach, the focus is

not on predicting which patient has
anatomic CAD but on identifying patients
at risk for specific adverse events, ie:
cardiac death or nonfatal MI, and on post-
MPI management strategies that might
reduce the risk of these outcomes.

care
Catheterization and revascularization can

be limited to those patients who may
benefit from these procedures using this
approach.

Incremental prognostic value
Given the constraints placed on physicians and

the health care system to practice clinically
effective and cost-effective medicine, it is
generally accepted that all diagnostic modalities
must be judged by the added or incremental
information they contribute over that provided
by the information known about the patient
before the test.

BAYESIAN THEORY
• The use of the Bayesian theory
incorporates the pretest risk of disease
and the sensitivity and specificity of the
test (likelihood ratio) to calculate the
posttest probability of coronary disease.
• The diagnostic power of the exercise test

is maximal when the pretest probability of
CAD is intermediate (30 – 70%)
BAYES THEOREM
Probability of CAD
Hence, the clinical value of MPI for prognostic

in CAD depends on the incremental or added
prognostic information yielded by this modality
over all data available before the test:
– clinical
– historical
– data from the nonimaging components of stress
testing

This analytic approach permits clinicians to

determine the true prognostic value of a test
and its actual contribution.

Several large studies reporting prognostic

analyses of MPI in cohorts using exercise,
vasodilator, or both types of stress and in
various clinical settings have highlighted its
added value.
Berman DS et al, J Am Coll Cardiol 27: 756, 1996
Hachamovitch R et al, Circulation 93: 905-914, 1996
Marwick TH et al, Am J Med 106: 172-178, 1999
Sharir T et al, Circulation 106: II-523, 2002 (abstr)
Vanzetto G et al, Circulation 100: 1521-1527, 1999
Zellweger MJ et al, J Am Coll Cardiol 37: 144-152, 2001
Added value of Gated-SPECT
• Left ventricular ejection fraction, when

measured by other modalities, has been shown
to risk-stratify patients for risk of subsequent
cardiac death.
Added value of Gated-SPECT
• Sharir and coworkers, demonstrated that that

post-stress LVEF, as measured by gated
SPECT, provided significant information over
the extend and severity of perfusion defect in
the prediction of cardiac death.
Sharir T et al, J Nucl Med 42: 831-837, 2001

Risk of adverse events after a
normal scan
• Extensive literature examining risk after a

normal stress  most studies report rates of
hard events (cardiac death or nonfatal MI) of
<1% per year of follow-up

Klocke FJ et al, J Am Coll Cardiol 42, 1318-1333, 2003
normal scan
The American Society of Nuclear Cardiology
published a position statement in 1997 stating that a
normal MPI study predicts a very low likelihood (<1%)
of adverse events such as cardiac death or myocardial
infarction for at least 12 months and that this level of
risk is independent of:
– gender
– age
– symptom status
– past history of CAD
– presence of anatomic CAD
– imaging technique or isotope (201Tl or 99mTc sestamibi)
Bateman TM et al, J Nucl Cardiol 4: 172-173, 1997

normal scan
However, published prognostic studies performed in
patients undergoing pharmacologic stress,
considered a population at higher risk and with more
co-morbidity than patients undergoing exercise stress,
have reported hard event rates of 1.3% to 2.7% per
year, suggesting that underlying clinical risk and prior
CAD may influence event rates after a normal MPI
Heller GV et al, J Am Coll Cardiol 26: 1202-1208, 1995

Shaw L et al, J Am Coll Cardiol 19: 1390-1398, 1992
Stratmann HG et al, Am J Cardiol 73: 647-652, 1994
Calnon DA et al, J Am Coll Cardiol 38: 1511-1517, 2001
Kang X et al, Am Heart J 138: 1025-1032, 1999
Amanullah AM et al, J Am Coll Cardiol 27: 803-809, 1996
normal scan
• Recently, an analysis of 7376 patients with normal
stress MPI addressed predictors of risk and its
temporal characteristics.
• Variables identified as markers of increased risk and

shortened time to risk:
– use of pharmacologic stress
– presence of known CAD
– DM (in particular, female diabetics)
– advanced age
Hachamovitch R et al, J Am Coll Cardiol 41: 1329-1340, 2003

Predicted events rates in the first and second
years after a normal stress MPI study
50 y.o. male, Ex, No 0.1

Hx CAD 0.1
80 y.o. male, Aden, 1.5

No Hx CAD 1.6
Year 1
Year 2
50 y.o. male, Hx 0.9
CAD 1.5
80 y.o. male, Hx 1.4

CAD 2.4
0 0.5 1 1.5 2 2.5 3
Predicted Hard Event Rate (%)

Hachamovitch R et al, J Am Coll Cardiol 41: 1329-1340, 2003
normal scan
• The increased baseline risk of patients after
normal MPI is limited to a subset of patients.
• As a whole, patients with normal MPI are at

very low risk
• Patients with known CAD who had normal MPI,

the temporal component of risk increased
rapidly.
Hachamovitch R et al, J Am Coll Cardiol 41: 1329-1340,2003

Expressing the extent and severity
of perfusion results
17 and 20-segment models of the left ventricle
13
1 7
2 6 8 12 14 18
19
3 5 9 20
11 15 17
4
10 16
11
1 5
6 10 12 16
2 4 17
7 9 13 15
3
8 14
Berman DS et al, J Am Coll Cardiol 26: 639-647, 1995

Berman DS et al, J Nucl Cardiol 11: 414-423, 2004
Cerqueira MD et al. Circulation 105: 539-542, 2002
Expressing the extent and severity
of perfusion results
Each segment is scored from 0 to 4
0 = normal
1 = equivocal reduction
2 = definite but moderate reduction
3 = severe reduction of tracer uptake
4 = absent uptake of radioactivity

Expressing the extent and
severity of perfusion results
• SSS  summed stress score
• SRS  summed rest score
• SDS  summed difference score

• The SSS, yields the perfusion analog of the
peak ejection fraction  represents
ischaemic and infarcted tissue
• The SRS is analogous to the resting ejection
fraction  is related to the amount of infarcted
or hibernating myocardium
• The SDS  expresses the amount of perfusion
defect reversibility
As a single overall prognostic variable, the SSS

(summed stress score) has been shown to be
the single most important predictor of hard
events

Event risk with abnormal scans
• Berman DS et al, Hurst’s The • Travin MI et al, J Nucl Cardiol
Heart, 2004, pp 525-565 11: 253-262, 2004
• Ladenheim ML et al, Am J • Thomas GS et al, J Am Coll

Cardiol 59: 270-277, 1987 Cardiol 43: 213-224, 2004
• Hachamovich R et al, • Heller GV et al, J Am Coll

Circulation 93: 905-914, 1996 Cardiol 26: 1202-1208, 1995
• Hachamovich R et al, • Kang X et al, Am Heart J 138:

Circulation 97: 535-543, 1998 1025-1032, 1999
• Marwick TH et al, Am J Med • Giri S et al, Circulation 105: 32-

106: 172-178, 1999 40, 2002
• Sharir T et al, J Nucl Med 42 : • Hachamovich R et al,

831-837, 2001 Circulation 105: 823-829, 2002
Risk
Extent/Severity of stress perfusion defects

• This relationship has been shown to be present

irrespective of:
– the type of stress performed
– the patient cohort examined
• clinical characteristics
• history of CAD
– the type of isotope used
• Variation in the relationship found in patients

with DM
– Risk was greater for patients with IDDM than

NIDDM
– and NIDDM greater than non-diabetic patients

Relationship between log relative hazard for predicted cardiac mortality
and SSS in IDDM, NIDDM and non-diabetic patients
IDDM
P<0.001
2.0
NIDDM
Log Relative Hazard
1.5
Non-diabetic
1.0
0.5
0.0
-0.5
-1.0
0 10 20 30 40 50
Summed Stress Score

P<0.001
4.5
4.2
4
3.5
P<0.01
3 2.9 2.9
2.7
2.5 2.3
CD
2
MI
1.5
1 0.8
0.6
0.5 0.3
0
Normal Mildly Abnl Mod Abnl Sev Abnl
2946 884 445 898
Mildly abnormal perfusion scan
Not only do scan data provide incremental
prognostic information over prescan
information, but also:
– advanced age
– prior CAD
– DM
– atrial fibrillation
– pharmacological stress
Hachamovich R et al, Circulation 93: 905-915, 1996
Hachamovich R et al, Circulation 107: 2899-2906, 2003
Moderately to severely abnormal
perfusion scan
Although both reversible and fixed stress
perfusion defects are predictors of prognosis,
those at highest risk of cardiac events are
patients with extensive stress-induced
abnormalities with:
– 201Tl
– 99mTc sestamibi
Ladenheim ML et al, Am J Cardiol 59: 270-277, 1987
– 99mTc tetrofosmin Vanzeto G et al, Circulation 100: 1521-1527, 1999
Travin MI et al, J Nucl Cardiol 11: 253-262, 2004
– dual-isotope Heller GV et al, J Am Coll Cardiol 26: 1202-1208, 1995

Hachamovitich R et al, Circulation 97: 535-543, 1998
Zellweger MJ et al, J Am Coll Cardiol 37: 144-152, 2001
Kang X et al, Am Heart J 138: 1025-1032, 1999
Hachamovitch R et al, Circulation 105: 823-829
Shaw LJ et al, J Nucl Med 44: 134-139, 2003
Nonperfusion MPI markers of risk
Transient ischemic dilatation (TID) of the LV
• TID is considered present when the LV cavity

appears to be significantly larger in the
poststress images than at rest.
• May often represent apparent cavity dilation

due to diffuse subendocardial ischemia
Weiss AT et al, J Am Coll Cardiol 9: 752-759, 1987

Mazzanti M et al, J Am Coll Cardiol 27: 1612-1620, 1996
• TID is considered to represent severe and

extensive ischemia and has been shown to be
highly specific for critical stenosis (> 90%
narrowing) in vessels that supply a large portion
of the myocardium (ie: proximal LAD or
multivessel lesions 90%)
Weiss AT et al, J Am Coll Cardiol 9: 752-759, 1987

Mazzanti M et al, J Am Coll Cardiol 27: 1612-1620, 1996
• TID in the setting of vasodilator stress has been

found to have similar implications as that
associated with exercise.
Chouraqui P et al, Am J Cardiol 66: 689-694, 1990

The prognostic value of TID as observed on

MPI has been reported by Abidov and
coworkers, who evaluated 1560 patients with
normal stress MPI with no LV enlargement who
were followed up for 2.3 years for hard and soft
cardiac events.
Abidov A et al, J Am Coll Cardiol 42: 1818-1825, 2003

They demonstrated that in patients with

otherwise normal MPI, TID is an independent
prognostic marker of total events even after
significant clinical variables, i.e. age, typical
angina and DM, are factored.
Abidov A et al, J Am Coll Cardiol 42: 1818-1825, 2003

Increased lung uptake of perfusion tracers
• It is generally accepted that the finding of increased

pulmonary uptake of 201Tl reflects increased
pulmonary capillary wedge pressure because of
either ischemia or nonischemic etiologies.
• Increased thallium lung uptake after exercise has

been shown to have incremental prognostic
information over myocardial perfusion defect
assessment.
Gill JB et al, N Engl J Med 317: 1486-1489, 1987

Nonperfusion markers in the setting
of pharmacological stress
The role of ST segment change
Marshall and colleagues found that although ST

depression was infrequent  only 17% of
patients had at least 1 mm ST depression and
5.3% had at least 2 mm ST depression, it was
both a univariate and multivarible predictor of
adverse outcomes, hence providing incremental
value over perfusion data alone
Marshall ES et al, Am Heart J 130: 58-66, 1995
Subsequent studies in larger populations

confirmed both the independent value of ST
depression and its incremental value over
perfusion variables for prediction of cardiac
death and MI
Hachamovitch R et al, Am J Cardiol 80: 426-433, 1997

Some studies, including larger studies using

cardiac death as solitary endpoint, have not
found ST depression during adenosine stress
to be predictive of outcome, whereas other
studies have.
Heller GV et al, J Am Coll Cardiol 26: 1202-1208, 1995
Stratmann HG et al, Am J Cardiol 73: 647-652, 1994
Lette J et al, Am Heart J 129: 880-886, 1995
Amanullah AM et al, Am J Cardiol 82: 725-730, 1998
Stratmann HG et al, Am Heart J 123: 317-323, 1992
Chikamori T et al, Jpn Circ J 57: 851-861, 1993
Clinical and hemodynamic responses to vasodilator stress
Normally, there is a mild rise in heart rate and

fall in blood pressure, particularly systolic blood
pressure, with adenosine or dipyridamole
infusion.
Ammanullah and colleagues found both a

higher heart rate at rest and a blunted heart
rate increase during adenosine infusion to be
univariate predictors of severe or extensive
CAD in women.
Amanullah AM et al, Am J Cardiol 79: 1319-1322, 1997

• Abidov and colleagues investigated 3444

patients (54% women, mean age 74.0 ± 8.4
years) who underwent adenosine MPI with no
additional exercise as an adjunct and were
followed up for 2.0 years.
• During this follow-up 224 cardiac deaths

occurred (6.5%)
Abidov A et al, Circulation 107: 2894-2899, 2003
Nonperfusion markers in the setting of
pharmacological stress
7
6
Predicted CD, %/yr
SSS=0-3
5
SSS=4-8
4
SSS=9-13
3 SSS>13
SSS>13
2 SSS=9-13
1 SSS=4-8
SSS=0-3
0
High Medium Low
Tercile Tercile Tercile
N=1146, N=1153, N=1145,
Range 1.28-3.13 Range 1.12-1.28 Range 0.67-1.12
Ratio Peak/Rest HR
Abidov A et al, Circulation 107: 2894-2899, 2003
Post-MPI patient management and
its prognostic implications
Scan results and physician action
Multiple studies to date have examined post-

MPI resource utilization using referral rates to
early cath and revascularization as measures of
physician action (early = first 60 – 90 days post-
MPI)
Staniloff HM et al, J Nucl Med 27: 1842-1848, 1984

Pryor DB et al, Am J Cardiol 53: 18-22, 1984
Clinical
symptoms
Normal scan
Cardiac cath Medical therapy

Subsequent results demonstrated that the

extent and severity of reversible defects shown
by the MPI result are the dominant factor
driving subsequent resource utilization

For any amount of ischemia present, the

presence of anginal symptoms results in the
highest referral rates, while asymptomatic
patients have the lowest referral rates

Post-MPI patient management
and its prognostic implications
Survival with medical therapy versus revascularization after stress MPI
6
5
Medical Rx
Lo Hazard Ratio
4
Revascularization
3
2
1
0
0 12.5% 25% 37.5% 50%

% Total Myocardium Ischemic
8 7.5
7
6
5
Lives saved
per 100 4 3.9 <60 yrs
treated with 3.4
3 60 - 80 yrs
Revasc vs.
Medical RX 2 >80 yrs
2
1.1
1 0.7
0.4
0.1
0
-1 -0.7
5 - 10% 10 - 20% >20%
% myocardium ischemic
Gated SPECT EF and ischemia add

incrementally to each other for prediction
of cardiac death and assessing potential
benefit from revascularization
Hachamovitch R et al, Circulation 106, 2002, (abstr)

Although EF was found to be a superior

predictor of cardiac death, only inducible
ischemia identified which patients
experienced a short-term benefit from
revascularization.

Post-MPI patient management
and its prognostic implications
For any degree of ischemia, the survival

benefit associated with revascularization
was greater for patients with reduced EF.

Treatment algorithms based on risk and potential benefits
Stress Gated SPECT
Mild/Moderate
No Ischemia
Ischemia
Ischemia >10%
(<10%)
Symptoms
controlled?
Medical Y N Catheterization
Therapy  Revasc.
TID
Lung uptake
ST changes
Motion abnorm

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2014 Myocardial Perfusion Imaging - Prof Libhaber 28-9-2017

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Myocardial Perfusion Imaging:

How does it affect clinical

Significant perfusion defect

Regional myocardial dysfunction

Exercise treadmill time

Meta-analysis: 19 exercise ECG studies,

Gibbons RJ et al, Circulation 2002;106:1883-1892

Santana-Boado C et al, J Nucl Med 1998;39:751-755

A new paradigm in patient management is

Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

With a risk-based approach, the focus is

Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

Catheterization and revascularization can

Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

Given the constraints placed on physicians and

Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

• The diagnostic power of the exercise test

Hence, the clinical value of MPI for prognostic

Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

This analytic approach permits clinicians to

Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

Several large studies reporting prognostic

• Left ventricular ejection fraction, when

• Sharir and coworkers, demonstrated that that

Sharir T et al, J Nucl Med 42: 831-837, 2001

• Extensive literature examining risk after a

Berman DS et al: Hurst’s The Heart, 2004, pp 525-565

Bateman TM et al, J Nucl Cardiol 4: 172-173, 1997

Heller GV et al, J Am Coll Cardiol 26: 1202-1208, 1995

• Variables identified as markers of increased risk and

Hachamovitch R et al, J Am Coll Cardiol 41: 1329-1340, 2003

50 y.o. male, Ex, No 0.1

80 y.o. male, Aden, 1.5

80 y.o. male, Hx 1.4

0 0.5 1 1.5 2 2.5 3

Predicted Hard Event Rate (%)

• As a whole, patients with normal MPI are at

• Patients with known CAD who had normal MPI,

Hachamovitch R et al, J Am Coll Cardiol 41: 1329-1340,2003

Berman DS et al, J Am Coll Cardiol 26: 639-647, 1995

Each segment is scored from 0 to 4

Berman DS et al, J Am Coll Cardiol 26: 639-647, 1995

• SSS  summed stress score

• SRS  summed rest score

• SDS  summed difference score

Berman DS et al, J Am Coll Cardiol 26: 639-647, 1995

As a single overall prognostic variable, the SSS

Hachamovitch R et al, Circulation 97: 535-543, 1998

• Ladenheim ML et al, Am J • Thomas GS et al, J Am Coll

• Hachamovich R et al, • Heller GV et al, J Am Coll

• Hachamovich R et al, • Kang X et al, Am Heart J 138:

• Marwick TH et al, Am J Med • Giri S et al, Circulation 105: 32-

• Sharir T et al, J Nucl Med 42 : • Hachamovich R et al,

Extent/Severity of stress perfusion defects

• This relationship has been shown to be present

• Variation in the relationship found in patients

– Risk was greater for patients with IDDM than

– and NIDDM greater than non-diabetic patients

Berman DS et al, J Am Coll Cardiol 41: 1125-1133, 2003

Summed Stress Score

– dual-isotope Heller GV et al, J Am Coll Cardiol 26: 1202-1208, 1995

• TID is considered present when the LV cavity

• May often represent apparent cavity dilation

Weiss AT et al, J Am Coll Cardiol 9: 752-759, 1987