Transcript 10/5/08 THauser -Myocardial Viability

A major teaching
hospital of Harvard
Medical School
Myocardial Viability
Thomas H. Hauser
MD, MMSc, MPH, FACC
Director of Nuclear Cardiology
Beth Israel Deaconess Medical Center
Instructor in Medicine
Harvard Medical School
Boston, MA
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Outline
• SPECT
• PET
• CMR
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Imaging Protocol
• Stress: Prone 99mTc-Sestamibi
• Rest: Prone 201Tl
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Case 1
Stress
Rest
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Slices
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Gated Slices
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Gated Slices: New Window
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QGS Results
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Clinical Data
• 58 year-old man with diabetes, hypertension, chronic renal
insufficiency, tobacco use, prior heroin abuse and liver
transplantation two years ago due to hepatitides B and C.
• One week prior to admission he was admitted to another
hospital with community acquired pneumonia. He was
discharged two days prior to admission.
• He presented on the day of admission with chest pain for
12 hours. In the ER he was noted to have anterior ST
elevation.
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Cardiac Catheterization
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Cardiac Catheterization
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Cardiac Catheterization
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Cardiac Catheterization
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Cardiac Catheterization
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Clinical Data
• He was referred for surgical revascularization.
The surgical team requested evaluation of
myocardial viability given his delayed
presentation and the concern for limited
myocardial salvage.
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Stress Protocol
• Dobutamine at 5 mcg/kg/min was infused for 21
minutes.
• HR 64  66
• SBP 124  134
• No symptoms
• No ECG changes
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Baseline ECG
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Clinical Data
Should our patient be revascularized?
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Dysfunctional but Viable Myocardium
LVEF 32%
LVEF 54%
Horn HR, Teichholz LE, Cohn PF, Herman MV, Gorlin R. Augmentation of left ventricular
contraction pattern in coronary artery disease by an inotropic catecholamine: the epinephrine
ventriculogram. Circulation 1974;49:1063-1071
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Dysfunctional but Viable Myocardium
• Hibernating
– Chronic ischemia or repetitive stunning
– Ultrastructural changes that result in
• Disassembly of contractile apparatus
– Recovery in weeks or months after revascularization
• Stunned
– Acute ischemia
– No ultrastructural changes
– Recovery in minutes to days after revascularization
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CABG in Patients with LV Dysfunction
Chareonthaitawee et al, JACC 2005;46:567
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Importance of Viable Myocardium
J Am Coll Cardiol 2002;39:1151
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Evaluation of Viability
Chareonthaitawee et al, JACC 2005;46:567
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Nuclear Techniques
• SPECT
– 201Tl
– 99mTc
– 123I Fatty Acids
– PET Agents
• PET
–
–
18FDG
11C
Acetate
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SPECT
•
201Tl
most commonly used
– Several protocols for use
• Stress – redistribution
• Rest – redistribution
– Usually imaged 4 to 24 hours after initial injection
– With or without reinjection
» Usually at 4 hours
– Perfusion tracer initially
• Ischemia is a sign of viability
– Membrane integrity tracer in the late phase
• K analog
– Assesses integrity of membrane and Na-K-ATPase
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SPECT
•
99mTc
also helpful
– Stress – rest protocol
– Perfusion tracer
– Ischemia is a sign of viability
– Membrane integrity tracer
• Trapped by active mitochondria
• PET agents act as with PET imaging
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201Tl
Uptake and Recovery of Function
Perrone-Filardi P, Pace L, Pratarto M, et al. Dobutamine echocardiography predicts improvement
of hypoperfused dysfunctional myocardium after revascularization in patients with coronary
artery disease. Circulation. 1995;91:2556-2565.
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Comparison of 201Tl and 99mTc
Udelson JE, Coleman PS, Metherall J, et al. Predicting recovery of severe regional ventricular
dysfunction. Comparison of resting scintigraphy with 201Tl and 99mTc-sestamibi. Circulation.
1994;89:2552-2561.
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PET
• All PET agents (18FDG, 11C acetate) assess cardiac
energy metabolism.
–
18FDG
imaging assesses glucose metabolism
• Ischemic myocardium generally favors glucose utilization
–
11C
acetate imaging assesses lipid metabolism
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Imaging Goal: High Quality Images
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Abnormal?
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Poor Image Quality
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Importance of Good Patient Preparation
• In the assessment of myocardial viability, the
quality and utility of the images is highly
dependent on appropriate patient preparation
– Inadequate patient preparation can lead to spurious
results or images with no diagnostic value
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Myocardial Energy Metabolism
• Cardiac myocytes are continuously active
– Require efficient use of energy resources
– Require continual repletion of energy substrates
• Faced with varying levels in supply
– Flexibility in substrate use
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Anaerobic Metabolism
• Inefficient
– Each glucose molecule
yields two ATP
• Requires glucose
• Does not require oxygen
• Lactate is the waste
product
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)
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Aerobic Metabolism
• Efficient
– Citric acid cycle produces
abundant ATP
• Can function with
multiple substrates
• Requires oxygen
• Water and CO2 are the
waste products
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)
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Myocardial Energy Metabolism
ketone bodies
amino acids
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)
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Myocardial Energy Metabolism
ketone bodies
amino acids
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)
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Glucose Handling
• Largely determined by the availability of glucose
in the blood stream
• Insulin is the major regulatory hormone
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Glucose Handling: Fasting
Glucagon
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Glucose Handling: Fasting
Glucose use
Glucagon
Gluconeogenesis
FFA
Glycogen
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Glucose Handling: Fed
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Glucose Handling: Fed
Glucose use
Gluconeogenesis
Glycogen
Fat storage
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Glucose Handling: Fed
Glucose use
Gluconeogenesis
Glycogen
Fat storage
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Glucose Handling: Diabetes (1)
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Glucose Handling: Diabetes (1)
Glucose use
Gluconeogenesis
FFA
Glycogen
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Glucose Handling: Diabetes (2)
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Glucose Handling: Diabetes (2)
Glucose use
Gluconeogenesis
FFA
Glycogen
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Glucose Handling
• In normal patients, feeding causes a rise in glucose and
insulin that restores glucose balance
– Uptake of glucose in peripheral tissues
• HEART
• In type 1 diabetics, feeding causes a rise in glucose while
insulin remains low/absent
– Continued gluconeogenesis and glucose conservation
• In type 2 diabetics, feeding causes a rise in glucose and
insulin but peripheral tissues are resistant to the action of
insulin
– Continued gluconeogenesis and glucose conservation
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FDG
Glucose: C6H12O6
FDG: C6H11O5
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FDG Uptake and Retention
glycogen
Insulin
glut
FDG
FDG – 6 – P
Aerobic Metabolism
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Goal of Patient Preparation
• Ensure that glucose is the primary substrate used
for myocardial energy metabolism
– Abundant Glucose
– Abundant Insulin
– Scarce FFA and other substrates
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Patient Preparation Protocols
•
•
•
•
Acipimox
Hyperinsulinemic/euglycemic clamp
IV glucose
Oral glucose
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Acipimox
• Potent inhibitor of peripheral lypolysis
– Drastically reduces FFA in blood
• As FFA are the principal alternative energy source
for the myocardium, glucose utilization increases
– Relatively independent of insulin and glucose levels
• Not FDA approved
– Used in Europe
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Hyperinsulinemic/Euglycemic Clamp
• Simultaneous infusions of insulin and glucose to
increase the insulin level while keeping the
glucose level from falling
– High insulin
– Normal glucose
– Low FFA
• High myocardial glucose utilization
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Glucose Loading
• Provide a large dose of oral or IV glucose
• Endogenous production of insulin
–
–
–
–
Supplemented with exogenous insulin if needed
Moderately high insulin
Normal glucose
Low FFA
• High myocardial glucose utilization
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Glucose Loading: Diabetes
• Exogenous insulin is required for appropriate
patient preparation with either type 1 or type 2
diabetes
– With type 1, there is little or no endogenous insulin
– With type 2, there is insulin resistance, requiring higher
insulin levels to ensure that insulin has an effect
• Observation of a falling blood sugar after
hyperglycemia is evidence of insulin action
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Patient Preparation Protocols
• Acipimox
– Easy
– Effective
– Not FDA approved
• Hyperinsulinemic/euglycemic clamp
– Difficult
– Effective
• IV/Oral Glucose Loading
– Relatively easy
– Almost always effective
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Insulin
• Many different kinds of insulin with varying
pharmacokinetics
–
–
–
–
–
–
–
Regular
NPH
Lispro
Lente
Ultralente
Glargine
Aspart
• Pharmocokinetics also vary with the route of
administration
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Insulin
• For patient preparation for FDG imaging, use
REGULAR insulin given IV
– Peak action of subcutaneous regular insulin occurs ~3
hours after the dose
– Peak action of IV regular insulin occurs ~15 minutes
after the dose
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BIDMC Patient Preparation Protocol
5. If the initial BS is >250, then give IV regular insulin according to the protocol below. If oral
glucose is given, recheck BS in 30 minutes and then give IV regular insulin according to the
same protocol.
Give IV regular insulin
None
BS ? 140
1 units
BS 141 to 160
2 units
BS 161 to 180
3 units
BS 181 to 200
4 units
BS 201 to 220
5 units
BS 221 to 240
6 units
BS 241 to 260
7 units
BS 261 to 280
8 units
BS 281 to 300
Notify Physician
BS >300
6. Check BS every 15 minutes.
 If BS is <140, inject FDG
 If BS continues to rise, give IV regular insulin according to the protocol above and
continue to check BS every 15 minutes
 If BS is falling but remains elevated, give IV regular insulin at half the dose according
to the protocol above and continue to check BS every 15 minutes
 If BS remains elevated after 90 minutes, contact the imaging physician
7. Have the patient eat a light meal 15 minutes after injection of FDG.
8. Continue to check BS every 30 minutes after injection of FDG to monitor for hypoglycemia.
9. Begin imaging 60-90 minutes after injection of FDG.
10. After imaging, monitor patient for 30 minutes and obtain BS. If BS >70 then the patient can
be discharged.
11. Upon discharge instruct the patient to:
 Beware of hypoglycemia. Encourage the patient to have a meal soon after discharge.
 Resume all prior medications.
If at any time during the protocol there is a question about how to proceed,
contact the imaging physician immediately.
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PET: 18FDG
Srinivasan G, Kitsiou AN, Bacharach SL, et al. [18F]Fluorodeoxyglucose Single Photon Emission
Computed Tomography : Can It Replace PET and Thallium SPECT for the Assessment of Myocardial
Viability? Circulation. 1998;97:843 - 850.
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PET: 18FDG
Srinivasan G, Kitsiou AN, Bacharach SL, et al. [18F]Fluorodeoxyglucose Single Photon Emission
Computed Tomography : Can It Replace PET and Thallium SPECT for the Assessment of Myocardial
Viability? Circulation. 1998;97:843 - 850.
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Case 2
• 45 year-old man with a history of CAD, diabetes,
CHF (LVEF 25%) who presented with repetitive
ICD firing due to recurrent VT.
• He was admitted to the hospital and found to have
a small NSTEMI. Cardiac catheterization was
performed and showed a 70% proximal LAD
stenosis, a totally occluded RCA, and occluded
SVGs to the LAD and PDA.
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Case 2
• The clinical team determined that his recurrent VT
was most likely to ischemia and consulted the CT
surgeons to determine his candidacy for a second
CABG. The surgeons requested a myocardial
viability study prior to proceeding.
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Case 2
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Case 2
• The study was interpreted as showing nonviability of the apex and inferior wall. The
remaining segments were viable.
• He subsequently underwent LAD stenting and has
done well since then.
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Case 3
A 59 year old with a history of diabetes,
hypertension and dyslipidemia sees his PCP
because of the new onset of dyspnea. His ECG
reveals LBBB. His PCP sends him for nuclear
imaging with exercise stress. During the test, he
has dyspnea at a low workload.
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Case 3: Slices
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Case 3: Gated Slices
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Case 3: Quantitative Data
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Case 3
He is referred for cardiac catheterization, which
reveals severe three vessel disease. The
consulting cardiac surgeon asks for a
determination of myocardial viability before
proceeding with surgical revascularization.
What can we do to further determine myocardial
viability?
• FDG
• Delayed enhancement MR
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Gd Contrast Kinetics in Myocardium
Circulation, Dec 1996; 94: 3318 - 3326
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Delayed
Contrast
Enhancement:
Bright is Dead
Circulation, Nov 1999; 100: 1992 - 2002
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Prediction of
Recovery of
Function
N Engl J Med 2000; 343:1445-1453
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Normal Myocardium
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Anterior/Apical Scar
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Ischemic CM with Viable Myocardium
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Case 3
The patient is sent for both FDG and delayed
enhancement MR.
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Case 3: FDG
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Case 3: DE-CMR
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Comparison of FDG and DE-CMR
Knuesel et al. Circulation. 2003;108:1095
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Spatial Resolution/Scar Imaging
Wagner et al. Lancet. 2003;361:374
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FDG and MR for Scar/Viability
FDG
• Images viable
myocardium
• Directly assesses
metabolism
• Established gold standard
for determining recovery
of function after
revascularization
•
•
•
•
DE-CMR
Images both scar and
viable myocardium
Directly assesses anatomy
Becoming clinically
established
Improved spatial
resolution compared to
FDG
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Dobutamine CMR
Mandapaka et al, J. Magn. Reson. Imaging 2006;24:499–512.
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Comparison of Techniques
CMR
SPECT with 18FDG
Chareonthaitawee et al, JACC 2005;46:567
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Summary
• SPECT
– Tl-201
– Tc-99m
• PET
– FDG
• CMR
– Late gadolinium enhancement
– Dobutamine
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