Harvard Medical School Myocardial Viability Thomas H. Hauser MD, MMSc, MPH, FACC Director of Nuclear Cardiology Beth Israel Deaconess Medical Center Instructor

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


Outline

• SPECT• PET• CMR


Imaging Protocol

• Stress: Prone 99mTc-Sestamibi• Rest: Prone 201Tl


Case 1

Stress Rest


Slices


Gated Slices


Gated Slices: New Window


QGS Results


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.


Cardiac Catheterization










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.


Stress Protocol

• Dobutamine at 5 mcg/kg/min was infused for 21 minutes.

• HR 64 66• SBP 124 134• No symptoms• No ECG changes


Baseline ECG


Clinical Data

Should our patient be revascularized?


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%


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


CABG in Patients with LV Dysfunction

Chareonthaitawee et al, JACC 2005;46:567


Importance of Viable Myocardium

J Am Coll Cardiol 2002;39:1151


Evaluation of Viability



Nuclear Techniques

• SPECT– 201Tl

– 99mTc

– 123I Fatty Acids

– PET Agents

• PET– 18FDG

– 11C Acetate


• 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


• 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


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.


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.


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


Imaging Goal: High Quality Images


Abnormal?


Poor Image Quality


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


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


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)


Aerobic Metabolism

• Efficient– Citric acid cycle produces

abundant ATP

• Can function with multiple substrates

• Requires oxygen

• Water and CO2 are the waste products




ketone bodiesamino acids





ketone bodiesamino acids


Glucose Handling

• Largely determined by the availability of glucose in the blood stream

• Insulin is the major regulatory hormone


Glucose Handling: Fasting

Glucagon


Glucagon

Glucose Handling: Fasting

GluconeogenesisGlycogen

FFA

Glucose use


Glucose Handling: Fed




Glucose use

Fat storage




Glucose use

Fat storage


Glucose Handling: Diabetes (1)




FFA

Glucose use






FFA

Glucose use


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


FDG

Glucose: C6H12O6 FDG: C6H11O5


FDG Uptake and Retention

glut FDG FDG – 6 – P

glycogen

Aerobic Metabolism

Insulin


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


Patient Preparation Protocols

• Acipimox• Hyperinsulinemic/euglycemic clamp• IV glucose• Oral glucose


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


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


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


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


Patient Preparation Protocols

• Acipimox– Easy

– Effective

– Not FDA approved

• Hyperinsulinemic/euglycemic clamp– Difficult

– Effective

• IV/Oral Glucose Loading– Relatively easy

– Almost always effective


Insulin

• Many different kinds of insulin with varying pharmacokinetics– Regular– NPH– Lispro– Lente– Ultralente– Glargine– Aspart

• Pharmocokinetics also vary with the route of administration


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


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.


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


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


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.


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.


Case 2


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.


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.


Case 3: Slices


Case 3: Gated Slices


Case 3: Quantitative Data


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


Gd Contrast Kinetics in Myocardium

Circulation, Dec 1996; 94: 3318 - 3326


Delayed Contrast

Enhancement:Bright is Dead

Circulation, Nov 1999; 100: 1992 - 2002


Prediction of Recovery of

Function

N Engl J Med 2000; 343:1445-1453


Normal Myocardium


Anterior/Apical Scar


Ischemic CM with Viable Myocardium


Case 3

The patient is sent for both FDG and delayed enhancement MR.


Case 3: FDG


Case 3: DE-CMR


Comparison of FDG and DE-CMR

Knuesel et al. Circulation. 2003;108:1095


Spatial Resolution/Scar Imaging

Wagner et al. Lancet. 2003;361:374


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


Dobutamine CMR

Mandapaka et al, J. Magn. Reson. Imaging 2006;24:499–512.


Comparison of Techniques

CMR

SPECT with 18FDG



Summary

• SPECT– Tl-201

– Tc-99m

• PET– FDG

• CMR– Late gadolinium enhancement

– Dobutamine

Documents

Harvard Medical School Myocardial Viability Thomas H. Hauser MD, MMSc, MPH, FACC Director of Nuclear Cardiology Beth Israel Deaconess Medical Center Instructor