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

History of Present Illness:History of Present Illness: 73 yo man with PMH of HTN, DM2, 73 yo man with PMH of HTN, DM2,

hyperlipidemia, and CAD presented on hyperlipidemia, and CAD presented on 5/12/04 with cc of fatigue and dyspnea.5/12/04 with cc of fatigue and dyspnea.

He was dx’d with CAD by angiogram on He was dx’d with CAD by angiogram on 3/30/04 and was also found to have 3/30/04 and was also found to have severe LV dysfxn at that time (LVEF severe LV dysfxn at that time (LVEF 20%).20%).

He did not have CP but did c/o He did not have CP but did c/o decreased exercise tolerance.decreased exercise tolerance.

HPI (continued)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.

Medical History:Medical History: PMH: HTN, hyperlipidemia, DM2, prostate PMH: HTN, hyperlipidemia, DM2, prostate

cancer, CADcancer, CAD

PSH: umbilical hernia repairPSH: umbilical hernia repair

Meds: zocor 40mg qd, asa 325mg qd, Meds: zocor 40mg qd, asa 325mg qd, toprol xl 50mg qd, hyzaar 50/12.5mg qd, toprol xl 50mg qd, hyzaar 50/12.5mg qd, aldactone 25mg qd, glipizide 5mg qd, aldactone 25mg qd, glipizide 5mg qd, carnitine 330mg tid, prevacid 15mg qdcarnitine 330mg tid, prevacid 15mg qd

Allergies: noneAllergies: none

Medical History (contin):Medical History (contin):

Social Hx: +Tobacco—smoked 2ppd for 40 yrs but stopped 6 weeks ago; no alcohol or illicit drug use.

Physical Exam:Physical Exam: VS: BP 147/67 HR 73 RR 16 T VS: BP 147/67 HR 73 RR 16 T

97.697.6

Alert and oriented x3Alert and oriented x3

Carotid pulses 2+ bilat without bruits Carotid pulses 2+ bilat without bruits

No Jugular venous distentionNo Jugular venous distention

Regular heart rhythm, normal s1/s2, Regular heart rhythm, normal s1/s2, Distant heart soundsDistant heart sounds

Physical Exam:Physical Exam: Both lungs clear but had scant bilat Both lungs clear but had scant bilat

end expiratory wheezingend expiratory wheezing

Abdomen non-tender with no Abdomen non-tender with no organomegalyorganomegaly

Skin dry, no edema, femoral pulses Skin dry, no edema, femoral pulses 2+ bilat without bruits, DP/PT pulses 2+ bilat without bruits, DP/PT pulses 2+ bilat2+ bilat

139

4.2

104 19

26 0.9121 8.6

11.1

34.1266

Hb A1c 5.9%

T Cholesterol 167

Triglycerides 73

HDL 41

LDL 107

BNP 394

Laboratory Data:Laboratory Data:

Laboratory Data:Laboratory Data:

12-Lead EKG—nsr, left axis deviation, 12-Lead EKG—nsr, left axis deviation, incomplete LBBB, LVH, when compared to incomplete LBBB, LVH, when compared to EKG from 3/24/04 there was now T wave EKG from 3/24/04 there was now T wave inversion in the lateral leadsinversion in the lateral leads

Chest X-ray—no acute pulmonary processChest X-ray—no acute pulmonary process

Results:Results:

Cardiac Angiogram (3/30/04):Cardiac Angiogram (3/30/04):2.2. Multivessel CAD.Multivessel CAD.3.3. Severely reduced LVEF.Severely reduced LVEF.4.4. Recommend CT surgery consult Recommend CT surgery consult

and optimization of medical and optimization of medical management.management.

Results: Echocardiogram (5/7/04):2. LAE, LVE.3. AK of inferior, apical, anterior, and

inferoseptal segments with severe HK of remaining segments.

4. LVEF ~ 15%.5. Eccentric LVH6. Severe MR, mild TR.

Management: It was determined after these

results that patient should undergo a viability study to determine if he would benefit from revascularization.

Is It Dead or Alive?

An Overview of Myocardial Viability Testing Stunned vs. Hibernating Myocardium

Hibernating myocardium Concept was developed in the late

1970’s based on 2 observations:2. That myocardial dysfunction present

before bypass surgery often reversed after surgery.

3. And that inotropic stimulation with epinephrine caused transient improvement in regional and global LV dysfunction in patients with CAD.

Ventriculogram with Epinephrine

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.”

Why This Is Important

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.

Support for Stunning as a Cause of Hibernation

1. In animal studies, repetitive stunning led to persistent LV dysfunction despite return of normal blood flow.

2. 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.

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.

Evaluation and treatment Ventriculography Dobutamine Echocardiography Myocardial Perfusion Imaging

(nulcear imaging with thallium, sestamibi, or PET)

MRI

Other Modalities Tissue Doppler Echocardiography

(TDE)/strain rate imaging Electroanatomic mapping Myocardial contrast

echocardiography

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

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

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%)

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

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.

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

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

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

Positron Emission Tomography

Ischemic cells use more glucose than normal.

Flourine-18 labeled deoxyglucose differentiates normal, hibernating and necrotic myocardium

Back to Our Patient He underwent thallium delayed

imaging. Images were obtained at rest, 10

minutes post injection, and at 24 hours post injection.

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.