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Harvard Medical School
Myocardial Viability
Thomas H. HauserMD, MMSc, MPH, FACC
Director of Nuclear CardiologyBeth Israel Deaconess Medical Center
Instructor in MedicineHarvard Medical School
Boston, MA
A major teaching hospital of Harvard Medical School
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Harvard Medical School
Outline
• SPECT• PET• CMR
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Harvard Medical School
Imaging Protocol
• Stress: Prone 99mTc-Sestamibi• Rest: Prone 201Tl
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Harvard Medical School
Case 1
Stress Rest
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Harvard Medical School
Slices
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Harvard Medical School
Gated Slices
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Harvard Medical School
Gated Slices: New Window
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Harvard Medical School
QGS Results
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Harvard Medical School
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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Harvard Medical School
Cardiac Catheterization
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Harvard Medical School
Cardiac Catheterization
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Harvard Medical School
Cardiac Catheterization
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Harvard Medical School
Cardiac Catheterization
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Harvard Medical School
Cardiac Catheterization
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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
Baseline ECG
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Harvard Medical School
Clinical Data
Should our patient be revascularized?
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Harvard Medical School
Dysfunctional but Viable Myocardium
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
LVEF 32% LVEF 54%
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Harvard Medical School
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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Harvard Medical School
CABG in Patients with LV Dysfunction
Chareonthaitawee et al, JACC 2005;46:567
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Harvard Medical School
Importance of Viable Myocardium
J Am Coll Cardiol 2002;39:1151
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Harvard Medical School
Evaluation of Viability
Chareonthaitawee et al, JACC 2005;46:567
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Harvard Medical School
Nuclear Techniques
• SPECT– 201Tl
– 99mTc
– 123I Fatty Acids
– PET Agents
• PET– 18FDG
– 11C Acetate
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Harvard Medical School
• 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
SPECT
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Harvard Medical School
• 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
SPECT
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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
Imaging Goal: High Quality Images
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Harvard Medical School
Abnormal?
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Harvard Medical School
Poor Image Quality
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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
Myocardial Energy Metabolism
ketone bodiesamino acids
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)
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Harvard Medical School
Myocardial Energy Metabolism
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)
ketone bodiesamino acids
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Harvard Medical School
Glucose Handling
• Largely determined by the availability of glucose in the blood stream
• Insulin is the major regulatory hormone
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Harvard Medical School
Glucose Handling: Fasting
Glucagon
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Harvard Medical School
Glucagon
Glucose Handling: Fasting
GluconeogenesisGlycogen
FFA
Glucose use
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Harvard Medical School
Glucose Handling: Fed
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Harvard Medical School
Glucose Handling: Fed
GluconeogenesisGlycogen
Glucose use
Fat storage
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Harvard Medical School
Glucose Handling: Fed
GluconeogenesisGlycogen
Glucose use
Fat storage
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Harvard Medical School
Glucose Handling: Diabetes (1)
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Harvard Medical School
Glucose Handling: Diabetes (1)
GluconeogenesisGlycogen
FFA
Glucose use
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Harvard Medical School
Glucose Handling: Diabetes (2)
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Harvard Medical School
Glucose Handling: Diabetes (2)
GluconeogenesisGlycogen
FFA
Glucose use
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Harvard Medical School
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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Harvard Medical School
FDG
Glucose: C6H12O6 FDG: C6H11O5
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Harvard Medical School
FDG Uptake and Retention
glut FDG FDG – 6 – P
glycogen
Aerobic Metabolism
Insulin
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Harvard Medical School
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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Harvard Medical School
Patient Preparation Protocols
• Acipimox• Hyperinsulinemic/euglycemic clamp• IV glucose• Oral glucose
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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
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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Harvard Medical School
BIDMC Patient Preparation Protocol
Patient Preparation Protocol for Myocardial Viability Imaging with FDG. 1. When the appointment is scheduled, obtain the following history:
Presence of diabetes Presence of renal insufficiency Presence of allergy to insulin (TRUE allergy only, not adverse reaction)
If the patient is allergic to insulin, it is unlikely that imaging will be successful and an alternative imaging method should be suggested. If the patient has renal insufficiency, the pharmacokinetics of insulin may be altered. Please consult with the imaging physician to determine if this patient preparation protocol should be followed. 2. Instruct patient to fast overnight prior to the procedure. Patients may take their usual medication with the exception of their diabetes medications. Oral diabetes medications should not be taken the morning of imaging. Patients taking insulin should take no regular insulin and half the dose of their usual long acting insulin. 3. Upon patient arrival on the day of imaging:
Place intravenous line Check initial blood sugar (BS)
4. Give glucose according to the following protocol:
Diabetes?
No Yes
Give oral glucose: Give oral glucose BS ?150 50 g BS ?150 25 g BS 151 to 250 25 g BS 151 to 250 12.5 g BS >250 None BS >250 None
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 BS ?140 None BS 141 to 160 1 units BS 161 to 180 2 units BS 181 to 200 3 units BS 201 to 220 4 units BS 221 to 240 5 units BS 241 to 260 6 units BS 261 to 280 7 units BS 281 to 300 8 units BS >300 Notify Physician 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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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.
PET: 18FDG
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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.
PET: 18FDG
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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 non-viability 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