Is It Dead or Alive?

1. Is It Dead or Alive? Eric J. Frischhertz, M.D.

2. History of Present Illness: • 73 yo man with PMH of HTN, DM2, hyperlipidemia, and CAD presented on 5/12/04 with cc of fatigue and dyspnea. • He was dx’d with CAD by angiogram on 3/30/04 and was also found to have severe LV dysfxn at that time (LVEF 20%). • He did not have CP but did c/o decreased exercise tolerance.

3. HPI (continued) • He could walk about 2 blocks before fatigue limited his activity. • He also reported LE swelling and orthopnea. • He did not have PND.

4. Medical History: • PMH: HTN, hyperlipidemia, DM2, prostate cancer, CAD • PSH: umbilical hernia repair • Meds: zocor 40mg qd, asa 325mg qd, toprol xl 50mg qd, hyzaar 50/12.5mg qd, aldactone 25mg qd, glipizide 5mg qd, carnitine 330mg tid, prevacid 15mg qd • Allergies: none

5. Medical History (contin): • Social Hx: +Tobacco—smoked 2ppd for 40 yrs but stopped 6 weeks ago; no alcohol or illicit drug use.

6. Physical Exam: • VS: BP 147/67 HR 73 RR 16 T 97.6 • Alert and oriented x3 • Carotid pulses 2+ bilat without bruits • No Jugular venous distention • Regular heart rhythm, normal s1/s2, Distant heart sounds

7. Physical Exam: • Both lungs clear but had scant bilat end expiratory wheezing • Abdomen non-tender with no organomegaly • Skin dry, no edema, femoral pulses 2+ bilat without bruits, DP/PT pulses 2+ bilat

8. Laboratory Data: 11.1 19 139 104 266 8.6 121 34.1 4.2 26 0.9 Hb A1c 5.9% T Cholesterol 167 Triglycerides 73 HDL 41 LDL 107 BNP 394

9. Laboratory Data: • 12-Lead EKG—nsr, left axis deviation, incomplete LBBB, LVH, when compared to EKG from 3/24/04 there was now T wave inversion in the lateral leads • Chest X-ray—no acute pulmonary process

10. Results: • Cardiac Angiogram (3/30/04): • Multivessel CAD. • Severely reduced LVEF. • Recommend CT surgery consult and optimization of medical management.

11. Results: • Echocardiogram (5/7/04): • LAE, LVE. • AK of inferior, apical, anterior, and inferoseptal segments with severe HK of remaining segments. • LVEF ~ 15%. • Eccentric LVH • Severe MR, mild TR.

12. Management: • It was determined after these results that patient should undergo a viability study to determine if he would benefit from revascularization.

13. Is It Dead or Alive? An Overview of Myocardial Viability Testing Stunned vs. Hibernating Myocardium

14. Hibernating myocardium • Concept was developed in the late 1970’s based on 2 observations: • That myocardial dysfunction present before bypass surgery often reversed after surgery. • And that inotropic stimulation with epinephrine caused transient improvement in regional and global LV dysfunction in patients with CAD.

15. Ventriculogram with Epinephrine

16. Diamond, et al. noted in 1978, “ischemic noninfarcted myocardium can exist in a state of function hibernation.” • This later led to the proposal by Rahimtoola of “hibernating myocardium.”

17. Why This Is Important

18. Pathophysiology • May result from repetitive myocardial stunning, which is different from hibernation in that it is caused by short term reduction in flow, a re-establishement of that flow, and subsequent LV dysfunction of limted duration.

19. Support for Stunning as a Cause of Hibernation • In animal studies, repetitive stunning led to persistent LV dysfunction despite return of normal blood flow. • Gradual increase in coronary stenosis in animals causes tissue supplied by the stenotic vessel to increase uptake of fluorine-18 labeled deoxyglucose, a glucose analog, which is a characteristic of hibernating myocardium.

20. Histopathologic Characteristics • Loss of contractile proteins (sarcomeres) without loss of cell volume in a substantial number of cells. • Glycogen-rich perinuclear zones adjacent to areas of numerous small mitochondria. • Nuclear changes with heterochromatin distributed evenly over the nucleaplasm • Substantial loss of sarcoplasmic reticulum.

21. Evaluation and treatment • Ventriculography • Dobutamine Echocardiography • Myocardial Perfusion Imaging (nulcear imaging with thallium, sestamibi, or PET) • MRI

22. Other Modalities • Tissue Doppler Echocardiography (TDE)/strain rate imaging • Electroanatomic mapping • Myocardial contrast echocardiography

23. Ventriculography • Asses wall motion by ventriculography then dtermine if there is improvement with NTG (to improve blood flow) or positive inotropic stimulation • Limited by subjective evaluation

24. Dobutamint Stress Echo • Evaluates the “inotropic reserve” • Viable myocardium shows improved global and regional contractile function. • An improved contractile response requires at least 50% viable myocytes in a given segment • The predictive value of the test is best when there is a biphasic response, i.e., improved contractile function with low dose infusion and worsening function with high dose

25. DSE continued • This represents an initial recruitment of contractile reserve followed by inducement of ischemia • Infusion with low dose dobutamine (2.5 to 5 mcg/kg/min) and increase incrementally while obtaining echo images at each dose • Sensitivity 84% (CI 82-86%) • Specificity 81% (CI 79-84%)

26. Nuclear Scan: Thallium • Thallium-201 is a potassium analog which can be detected by single photon emission computed tomography (SPECT) • Uptake by myocardial cells depends on an active transport process requiring intact sarcolemmal membranes and adequate ATP stores • Images are obtained at rest and 4 hours later • In normal myocardium, intial uptake is high but decreases rapidly within hours

27. Thallium continued • In hibernating myocardium, initial uptake is low but increases over time due to thallium redistribution. • Uptake of greater than 50% of that in the normal area is the best predictor of functional recovery after revascularization.

28. Thallium Protocols • In addition to the 4 hour protocol, there have been studies with reimaging at 24 hours and also with reinjection of a smaller dose of thallium prior to obtaining redistribution images • Both protocols have better sensitivity that the intial protocol

29. Technetium-99m Sestamibi • Sestamibi is a lipphilic cationic compound. The uptake across myocardial mebmranes is passive and requires the presence of intact electrochemical membrane gradients • There is limited redistribution after initial uptake which would appear to limit its usefulness in determining viability

30. Sestamibi Continued • However, multiple studies comparing sestaimibi with thallium have shown that sestamibi produces results similar to that of thallium • This would indicate that the kinetics of sestamibi are more complex under low flow conditions than can be explained by a simple flow dependent model

31. Positron Emission Tomography • Ischemic cells use more glucose than normal. • Flourine-18 labeled deoxyglucose differentiates normal, hibernating and necrotic myocardium

33. Back to Our Patient • He underwent thallium delayed imaging. • Images were obtained at rest, 10 minutes post injection, and at 24 hours post injection.

36. Findings • 17% of the left ventricular myocardium, located in the inferior and the inferolateral wall, demonstrates viability by thallium scintigraphy. 12% of the myocardium in the same region has no viability and represents scar.