Tagenarayan Niwaz

January 23, 2015

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

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

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

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

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

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

Incremental Prognostic Value N = 2,200 patientsMPI Further risk stratification

Revascularization better if >10% of ischemic myocardium involved

N= 10,000 patients with suspected CAD studied by stress MPI

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

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

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

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

Extent Of IschemiaAfter Statin

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

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

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

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

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

Apex consistent with infarctionHypertrophied septum

Silent Ischemia In The Anterior, Lateral, And Inferior Wall in HCM

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

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

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

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

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

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

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

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

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

Large apical reversible defect

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%

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

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

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

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