1. Myocardial Viability Thomas H. Hauser MD, MMSc, MPH, FACC
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

2. Outline
SPECT
PET
CMR

3. Imaging Protocol
Stress: Prone 99mTc-Sestamibi
Rest: Prone 201Tl

4. Case 1
Stress
Rest

5. Slices

6. Gated Slices

7. Gated Slices: New Window

8. QGS Results

9. 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.

10. Cardiac Catheterization

11. Cardiac Catheterization

12. Cardiac Catheterization

13. Cardiac Catheterization

14. Cardiac Catheterization

15. 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.

16. Stress Protocol Dobutamine at 5 mcg/kg/min was infused for 21 minutes.
HR 64  66
SBP 124  134
No symptoms
No ECG changes

17. Baseline ECG

18. Should our patient be revascularized?
Clinical Data
Should our patient be revascularized?

19. 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:

20. 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

21. CABG in Patients with LV Dysfunction
Chareonthaitawee et al, JACC 2005;46:567

22. Importance of Viable Myocardium
J Am Coll Cardiol 2002;39:1151

23. Evaluation of Viability
Chareonthaitawee et al, JACC 2005;46:567

24. Nuclear Techniques SPECT PET 201Tl 99mTc 123I Fatty Acids PET Agents
18FDG
11C Acetate

25. 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

26. SPECT 99mTc also helpful PET agents act as with PET imaging
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

27. 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 ;91:

28. 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 ;89:

29. 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

30. Imaging Goal: High Quality Images

31. Abnormal?

32. Poor Image Quality

33. 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

34. 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

35. Anaerobic Metabolism Inefficient Requires glucose
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)

36. Aerobic Metabolism Efficient Can function with multiple substrates
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)

37. Myocardial Energy Metabolism
ketone bodies
amino acids
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)

38. Myocardial Energy Metabolism
ketone bodies
amino acids
Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)

39. Glucose Handling
Largely determined by the availability of glucose in the blood stream
Insulin is the major regulatory hormone

40. Glucose Handling: Fasting
Glucagon

41. Glucose Handling: Fasting
Glucose use
Glucagon
Gluconeogenesis
Glycogen
FFA

42. Glucose Handling: Fed

43. Glucose Handling: Fed
Glucose use
Gluconeogenesis
Glycogen
Fat storage

44. Glucose Handling: Fed
Glucose use
Gluconeogenesis
Glycogen
Fat storage

45. Glucose Handling: Diabetes (1)

46. Glucose Handling: Diabetes (1)
Glucose use
Gluconeogenesis
Glycogen
FFA

47. Glucose Handling: Diabetes (2)

48. Glucose Handling: Diabetes (2)
Glucose use
Gluconeogenesis
Glycogen
FFA

49. 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

50. FDG
Glucose: C6H12O6
FDG: C6H11O5

51. FDG Uptake and Retention
glycogen
Insulin
glut
FDG
FDG – 6 – P
Aerobic Metabolism

52. 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

53. Patient Preparation Protocols
Acipimox
Hyperinsulinemic/euglycemic clamp
IV glucose
Oral glucose

54. 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

55. 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

56. 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

57. 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

58. Patient Preparation Protocols
Acipimox
Easy
Effective
Not FDA approved
Hyperinsulinemic/euglycemic clamp
Difficult
IV/Oral Glucose Loading
Relatively easy
Almost always effective

59. Insulin Many different kinds of insulin with varying pharmacokinetics
Regular
NPH
Lispro
Lente
Ultralente
Glargine
Aspart
Pharmocokinetics also vary with the route of administration

60. 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

61. BIDMC Patient Preparation Protocol

62. 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 ;97:

63. 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 ;97:

64. 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.

65. 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.

66. Case 2

67. 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.

68. 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.

69. Case 3: Slices

70. Case 3: Gated Slices

71. Case 3: Quantitative Data

72. 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

73. Gd Contrast Kinetics in Myocardium
Circulation, Dec 1996; 94:

74. Delayed Contrast Enhancement: Bright is Dead
Circulation, Nov 1999; 100:

75. Prediction of Recovery of Function
N Engl J Med 2000; 343:

76. Normal Myocardium

77. Anterior/Apical Scar

78. Ischemic CM with Viable Myocardium

79. Case 3
The patient is sent for both FDG and delayed enhancement MR.

80. Case 3: FDG

81. Case 3: DE-CMR

82. Comparison of FDG and DE-CMR
Knuesel et al. Circulation. 2003;108:1095

83. Spatial Resolution/Scar Imaging
Wagner et al. Lancet. 2003;361:374

84. FDG and MR for Scar/Viability
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

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

86. Comparison of Techniques
CMR
SPECT with 18FDG
Chareonthaitawee et al, JACC 2005;46:567

87. Summary SPECT PET CMR Tl-201 Tc-99m FDG Late gadolinium enhancement
Dobutamine