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

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Presentation on theme: "Harvard Medical School Myocardial Viability Thomas H. Hauser MD, MMSc, MPH, FACC Director of Nuclear Cardiology Beth Israel Deaconess Medical Center Instructor."— Presentation transcript:

1 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 A major teaching hospital of Harvard Medical School

2 Harvard Medical School Outline SPECT PET CMR

3 Harvard Medical School Imaging Protocol Stress: Prone 99m Tc-Sestamibi Rest: Prone 201 Tl

4 Harvard Medical School Case 1 Stress Rest

5 Harvard Medical School Slices

6 Harvard Medical School Gated Slices

7 Harvard Medical School Gated Slices: New Window

8 Harvard Medical School QGS Results

9 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.

10 Harvard Medical School Cardiac Catheterization

11 Harvard Medical School Cardiac Catheterization

12 Harvard Medical School Cardiac Catheterization

13 Harvard Medical School Cardiac Catheterization

14 Harvard Medical School Cardiac Catheterization

15 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.

16 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

17 Harvard Medical School Baseline ECG

18 Harvard Medical School Clinical Data Should our patient be revascularized?

19 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: LVEF 32% LVEF 54%

20 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

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

22 Harvard Medical School Importance of Viable Myocardium J Am Coll Cardiol 2002;39:1151

23 Harvard Medical School Evaluation of Viability Chareonthaitawee et al, JACC 2005;46:567

24 Harvard Medical School Nuclear Techniques SPECT – 201 Tl – 99m Tc – 123 I Fatty Acids –PET Agents PET – 18 FDG – 11 C Acetate

25 Harvard Medical School 201 Tl 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

26 Harvard Medical School 99m Tc 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

27 Harvard Medical School 201 Tl 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:

28 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 201 Tl and 99m Tc-sestamibi. Circulation. 1994;89:

29 Harvard Medical School PET All PET agents ( 18 FDG, 11 C acetate) assess cardiac energy metabolism. – 18 FDG imaging assesses glucose metabolism Ischemic myocardium generally favors glucose utilization – 11 C acetate imaging assesses lipid metabolism

30 Harvard Medical School Imaging Goal: High Quality Images

31 Harvard Medical School Abnormal?

32 Harvard Medical School Poor Image Quality

33 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

34 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

35 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)

36 Harvard Medical School Aerobic Metabolism Efficient –Citric acid cycle produces abundant ATP Can function with multiple substrates Requires oxygen Water and CO 2 are the waste products Based on Autumn Cuellar (Bioengineering Institute, University of Auckland)

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

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

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

40 Harvard Medical School Glucose Handling: Fasting Glucagon

41 Harvard Medical School Glucagon Glucose Handling: Fasting Gluconeogenesis Glycogen FFA Glucose use

42 Harvard Medical School Glucose Handling: Fed

43 Harvard Medical School Glucose Handling: Fed Gluconeogenesis Glycogen Glucose use Fat storage

44 Harvard Medical School Glucose Handling: Fed Gluconeogenesis Glycogen Glucose use Fat storage

45 Harvard Medical School Glucose Handling: Diabetes (1)

46 Harvard Medical School Glucose Handling: Diabetes (1) Gluconeogenesis Glycogen FFA Glucose use

47 Harvard Medical School Glucose Handling: Diabetes (2)

48 Harvard Medical School Glucose Handling: Diabetes (2) Gluconeogenesis Glycogen FFA Glucose use

49 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

50 Harvard Medical School FDG Glucose: C 6 H 12 O 6 FDG: C 6 H 11 O 5

51 Harvard Medical School FDG Uptake and Retention glut FDG FDG – 6 – P glycogen Aerobic Metabolism Insulin

52 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

53 Harvard Medical School Patient Preparation Protocols Acipimox Hyperinsulinemic/euglycemic clamp IV glucose Oral glucose

54 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

55 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

56 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

57 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

58 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

59 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

60 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

61 Harvard Medical School BIDMC Patient Preparation Protocol

62 Harvard Medical School Srinivasan G, Kitsiou AN, Bacharach SL, et al. [ 18 F]Fluorodeoxyglucose Single Photon Emission Computed Tomography : Can It Replace PET and Thallium SPECT for the Assessment of Myocardial Viability? Circulation. 1998;97: PET: 18 FDG

63 Harvard Medical School Srinivasan G, Kitsiou AN, Bacharach SL, et al. [ 18 F]Fluorodeoxyglucose Single Photon Emission Computed Tomography : Can It Replace PET and Thallium SPECT for the Assessment of Myocardial Viability? Circulation. 1998;97: PET: 18 FDG

64 Harvard Medical School 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 Harvard Medical School 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 Harvard Medical School Case 2

67 Harvard Medical School 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 Harvard Medical School 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 Harvard Medical School Case 3: Slices

70 Harvard Medical School Case 3: Gated Slices

71 Harvard Medical School Case 3: Quantitative Data

72 Harvard Medical School 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 Harvard Medical School Gd Contrast Kinetics in Myocardium Circulation, Dec 1996; 94:

74 Harvard Medical School Delayed Contrast Enhancement: Bright is Dead Circulation, Nov 1999; 100:

75 Harvard Medical School Prediction of Recovery of Function N Engl J Med 2000; 343:

76 Harvard Medical School Normal Myocardium

77 Harvard Medical School Anterior/Apical Scar

78 Harvard Medical School Ischemic CM with Viable Myocardium

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

80 Harvard Medical School Case 3: FDG

81 Harvard Medical School Case 3: DE-CMR

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

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

84 Harvard Medical School 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

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

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

87 Harvard Medical School Summary SPECT –Tl-201 –Tc-99m PET –FDG CMR –Late gadolinium enhancement –Dobutamine


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