1. Imaging techniques for the
Assessment of
Myocardial Hibernation
Michael G. Katz, MD
Fellow in Cardiovascular Disease
Instructor in Psychiatry
October 20, 2011

2. • CAD is the primary cause of decreased LVEF
• Drugs such as ACEis, ARBs, BB, and aldosterone antagonists have
improved the prognosis of heart failure, but the outcome with medical
treatment remains poor.
• Until recently, there was no data from multicentre trials assessing the
value of revascularization procedures for the relief of HF symptoms.
• However, single-centre, observational studies on HF of ischemic
origin suggest that revascularization may lead to symptomatic
improvement and potentially improve cardiac function.
• CASS registry
• mortality of patients with LV dysfunction increased rapidly with
reduction in LVEF, and that one-year mortality was reduced
from 24% on medical therapy to 15% after revascularisation in
patients with LVEF below 25% Circulation 2006;114:1202
Curr Opin Cardiol 2008;23:148
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6. "The take-home message for me is that the STICH trial supports bypass
surgery on top of best medical therapy vs medical therapy alone to
reduce cardiovascular morbidity and mortality and that many patients
who are now treated for heart failure without ever being assessed for the
potential of having angiographic coronary disease should be evaluated for
that, because [coronary disease] does not present the same way in every
patient,” […] "Heart failure without angina shouldn't exclude
patients from an angiographic evaluation."
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7. General considerations
• perioperative mortality in patients with left ventricular dysfunction is
relatively high
• it is important to revascularise only patients who will obtain overall
benefit
• When angina is a dominant symptom, the decision is relatively simple
• When symptoms of left ventricular dysfunction dominate, the decision
is more difficult because it is harder to distinguish between permanent
left ventricular dysfunction and dysfunction that might improve after
treatment.
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8. • Common causes of ischemic LV dysfunction are:
• full-thickness myocardial infarction
• partial thickness infarction
• myocardial stunning, and
• myocardial hibernation
• Complicated by the potential coexistence of different states in the same
patient or even in the same myocardial region.
• Imaging techniques can detect and assess
• myocardial viability,
• metabolism,
• perfusion, and
• Function
Multiple techniques to assess the above, but most hospitals either do
not have access to them all or lack expertise in some of them.
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9. Definitions
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10. Viable
“myocardial cells that are alive and hence also the myocardium that they
constitute.”
Although individual myocytes may be viable or non-viable, CLINCALLY,
the myocytes exist within the macroscopic myocardium
Partially Viable
Nonviable
Fully Viable Partial-thickness infarction
Scarred
Full-thickness infarction
No remaining myocytes
The term “viable” implies nothing with regard to contractile state.
Viable myocardium may contract normally or it may be dysfunctional, de-
pending on other circumstances.
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11. Stunned
Contractile dysfunction of viable myocardium caused by a
brief period of ischemia followed by restoration of perfusion
• ? free radicals and a transitory overload of calcium
• Examples:
• Myocardial infarction that is aborted by thrombolysis
• After an episode of unstable angina
• After ischemia induced by exercise testing
• Dysfunction may persist from an hour to several days, but
function ultimately returns to normal if normal perfusion is
maintained
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12. Hibernating (the most difficult to understand)
A state of contractile dysfunction in viable myocardium, but in the
setting of chronic ischemic heart disease
• hibernating myocardium requires an intervention such as
revascularisation for recovery
• ALTHOUGH: medical therapy might also be effective in relieving
hibernation by abolishing ischemia. You don’t know if
myocardium is
hibernating or just
dead until tissue is
Retrospective definition revascularized…
But most surgeons or
interventionalists
won’t revasc unless
they know tissue is
hibernating.
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13. Prospective definition of hibernation
One definition: “viable and dysfunctional myocardium”
Partially Viable Nonviable
Fully Viable Partial-thickness infarction Scarred
Full-thickness infarction
No remaining myocytes
However, not all viable myocardium may contract… it may be
tethered to infarcted tissue.
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14. • The demonstration of inducible ischemia in the relevant
section of myocardium is a helpful addition to the definition
since hibernation is an ischemic syndrome
• It is unlikely to be present in the absence of inducible
ischemia.
• Thus, the most useful surrogate definition of hibernation is
viable and dysfunctional myocardium in which impaired
perfusion reserve leads to inducible ischemia.
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15. Pathophysiological definition on hibernation
Hibernation was originally defined as “a state of persistently impaired
myocardial and left ventricular function at rest due to reduced coronary
blood flow that can be partially or completely restored to normal if the
myocardial oxygen supply/demand ratio is favourably altered.”
• It is still controversial whether or not perfusion is reduced at rest
• Although, we know that it is not always reduced.
• Therefore perfusion is usually omitted from the definition of
hibernation.
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16. Prevalance of recoverable function?
J Am Coll Cardiol 1996;28:948
Recovery is seen, on average, in 55–60% of dysfunctional
segments, even in patients with baseline ejection fraction below
40%
May be an underestimate: 1) completeness of revasc is rarely
assessed and 2) tissue may take up to a year to recover. 17

17. EKG
Q waves – NOT helpful
• no relationship between the presence and extent of Q waves after
myocardial infarction and infarct size assessed by myocardial perfusion
imaging
• 60% of regions with Q waves have viable myocardium detected by
imaging techniques
• QR complexes DO NOT contain more viable tissue than QS complexes
• No correlation with QRS scoring and LVEF
Circulation 1986;73:951
Am J Cardiol 2002;89:1171
Am Heart J 2002;144:865
Heart 1999;82:663
Ann Intern Med 1991;114:264
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18. ST segment – Somewhat helpful
• ST-segment elevation at rest in leads with Q waves is associated with more severe
wall-motion abnormalities, less contractile reserve and greater end-systolic volume
• extreme case, this is seen as ST elevation of aneurysm formation
• ST elevation developing during exercise is a marker of maintained viability, and late
improvement in LV function after myocardial infarction is more common when the ST
segment is elevated during dobutamine echocardiography.
• Inducible perfusion abnormalities assessed by SPECT have been seen in 94% of
patients with exercise-induced ST elevation and in 50% with pseudonormalisation of
the T wave but without ST elevation.
• The combination of ST elevation and reciprocal ST depression increases the accuracy
for detection of viable myocardium
• ST elevation during exercise predicts FDG uptake with a sensitivity of 82% and
specificity of 100%
• functional recovery data re: exercise ST elevation is contradictory
Heart 1997;77:115 Am J Cardiol 1998;82:148–53.
Am Heart J 1999;137:500 Am J Cardiol 1998;81:12–6.
J Am Coll Cardiol 1996;27:599 Am J Cardiol 1999;84:535–9.
J Am Coll Cardiol 1992;19:948 Eur Heart J 2000;21:446
J Am Coll Cardiol 1995;25:1032
J Am Coll Cardiol 1999;33:620
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19. T waves – NOT useful
• Dobutamine-induced T-wave changes are associated with greater wall-
motion abnormalities at rest and during stress, but the finding is not
sufficiently accurate to predict residual myocardial viability after infarction
(Am J Cardiol 1999;84:535)
QT dispersion (maximum QT interval minus minimum QT interval)– Useful
• After infarction, low QT dispersion is a marker of residual viable
myocardium (Eur Heart J 2000;21:446)
• QT dispersion of less than 70 ms has a sensitivity of 85% and a specificity
of 82% for predicting FDG uptake in the region of infarction, and 83% and
71%, respectively, for predicting functional recovery after revascularization
(Circulation 1997;96:3913).
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20. Positron emission tomography
Not only can the distribution of molecules be imaged, but their uptake
can be quantified
It is possible to assess:
• myocardial perfusion
• glucose utilization
• fatty acid up-take and oxidation
• oxygen consumption
• Contractile function, and
• presynaptic and postsynaptic neuronal activity
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21. FDG and ammonia
F-fluoro-2-deoxy-DD-glucose (FDG) is a glucose analogue that is taken
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up by viable cardiac myocytes in the same way as glucose, but its
subsequent metabolism is blocked and it remains within the myocyte
• tracer of exogenous glucose uptake and, by inference, of myocardial
viability
N-ammonia is a perfusion tracer that is avidly extracted and retained in
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viable myocytes by incorporation into glutamine
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22. FDG and ammonia studies have most commonly been combined
because the relationship between glucose metabolism and perfusion
differs in the different types of myocardium:
Myocardium FDG Ammonia
Stunned Nl Nl
Hibernating Nl or
Infarcted
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23. It is not clear why the pattern of “perfusion-metabolism mismatch” is so
characteristic of hibernating.
• uncertain whether the dominant feature is reduction of ammonia
uptake or increase in FDG uptake, or a mixture of both
Image analysis is often qualitative and based upon relative regional
comparisons of uptake.
The semiquantitative approach normalises FDG uptake to the segment
with maximum ammonia uptake (presumed to be normal
myocardium), which allows above-normal uptake of FDG uptake to be
assessed.
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24. Hybrid imaging
• Even when a PET camera is available, imaging may be restricted to
FDG because the half-lives of 13N and 15O are too short to allow
ammonia and water imaging without an on-site cyclotron.
• FDG imaging for myocardial viability has been combined with single
photon perfusion tracers, such as thallium and MIBI.
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25. Single-photon emission computed tomography
Thallium-201
• Thallium has been used extensively for identifying myocardial viability
and hibernation; it was the first tracer to be used for this purpose
• potassium analogue and myocardial uptake depends upon regional
flow and upon an intact sarcolemmal membrane to facilitate
transport
• information on both perfusion and cell viability
• Unfavorable properties:
• Low-energy X-ray emission
• Long half-life
• appreciable radiation exposure to patients
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26. Late-redistribution imaging shows increased uptake in up to 54% of
defects that are fixed 4 h after stress injection.
Reinjection leads to increased uptake in 49% of segments and nine
studies using this technique had positive and negative predictive
accuracies of 69% and 89%, respectively, for improvement of
function after revascularisation.
N Engl J Med 1990;66:394
Am J Cardiol 1995;75:17A
Circulation 1996;94:2674

27. Technetium-99m
Most widely reported technetium agent is Tc-99m-2 methoxyisobutylisonitrile (MIBI).
Advantages over thallium
• such as a shorter half-life with lower radiation exposure to the patient, a higher-
energy gamma emission that reduces soft-tissue attenuation, and the potential for
ECG-gated acquisition
Disadvantages
• since uptake depends on both perfusion and viability, and viability may be
underestimated in areas with reduced perfusion at rest.
• In contrast, thallium uptake is independent of perfusion once redistribution is
complete.
Some studies have found MIBI to be inferior to thallium for identifying viability, but
others have found the two to be comparable (European Heart Journal 2004:25; 815)
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28. ECG-gated SPECT
Although the SPECT images are not high resolution, it is possible to
assess myocardial thickening, as well as motion, since myocardial counts
are linearly related to myocardial thickness.
Thickening is a better assessment of regional function than
motion.
• infarcted regions can appear to move if dragged by neighboring normal
regions, and normal regions can appear akinetic if regional motion is
opposed by translation of the whole heart.
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29. Stress Echo
• Stress echocardiography allows inducible myocardial ischemia to be
detected indirectly by direct visualization of the left ventricular
dysfunction.
• Normally performed on cessation of exercise and within 2 min because
exercise-induced abnormalities are normally transitory.
• In patients who are unable to exercise, dobutamine and dipyridamole
are alternatives, but dobutamine is generally preferred
• more readily induces ischaemia
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30. Myocardial infarction, particularly transmural infarction, leads to thinned and
akinetic segments at rest. However, if the function of an akinetic
segment improves with stress, this implies the presence of viable
myocardium.
• Low doses of dobutamine (5 lg/kg/min) are normally sufficient to provoke
this response
• If there is also inducible ischemia, then a biphasic response is
• seen with initial improvement in function and deterioration at higher doses.
• The extent of myocardial hibernation determined in this way predicts
outcome after revascularisation.
• The reported accuracy of stress echocardiography for predicting recovery of
segmental function after revascularisation varies, with sensitivities of 70%
to 85% and specificities of 80% to 90%.
J Am Coll Cardiol 1999;33:1848
Am J Cardiol 1998;82:1339
Circulation 1999;100:141
Eur Heart J 2000;13:1091
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31. MRI
Provides information regarding:
• anatomy,
• function, and
• blood flow
Limitations:
• including its temporal resolution,
• the need for breath-holding with some acquisition sequences, and
• difficulties with claustrophobic patients and pts with pacemakers
Two different approaches to the assessment of patients with chronic ischaemic
LV fx:
1.Assess myocardial morphology, function at rest, and contractile reserve
during pharmacological stress.
2.Image myocardial infarction and evaluate the microcirculation using
paramagnetic contrast agents. 32

32. Myocardial thickness and contractile reserve
High-resolution and high-contrast images, MRI is now the standard
against which other techniques are compared for the measurement of
ventricular volumes, ejection fraction, myocardial mass, and regional wall
motion.
• Spatial resolution is 1–2 mm and temporal resolution is between 20
and 50 ms.
Infarcts more than four months-old may become akinetic and thinned.Old
infarctions with an end-diastolic myocardial thickness of less than 5.5
mm have significantly reduced FDG uptake and this has been used as the
threshold for clinically significant myocardial viability
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33. • 94% sensitivity but 52% specificity for predicting recovery of
regional function 3 months after revascularisation.
• segments of less than 5.5 mm in thickness are not very likely to be
hibernating
• segments of more than 5.5 mm in thickness may be hibernating or
may simply consist of partial-thickness infarction
Am Heart J 1939;18:647
Circulation 1995;91:1006
J Am Coll Cardiol1998;31:1040
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34. Contractile reserve – Doubutamine stress MRI
Essentially similar concept as doubutamine stress echo
Sensitivity of 89% and specificity of 94% for detecting hibernation.
In a direct comparison between dobutamine MRI and SPECT in patients
with ischemic LV dysfunction undergoing revascularisation, MRI had a low
sensitivity (50%) but high specificity (81%), whereas the nuclear
echniques were more sensitive, but less specific for predicting recovery of
regional function. (Circulation 1998;98:1869)
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35. Contrast/ Perfusion MRI
Extracellular paramagnetic contrast agents, such as gadolinium
• exchange rapidly between the intravascular and extracellular
interstitial space, but they do not pass through the intact membranes
of cardiac myocytes so they are not direct markers of viability
• used to detect regional abnormalities of myocardial perfusion
• mechanism of late enhancement is not clear, but it is possibly related
to an increase of the extra-cellular matrix late after infarction
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36. Comparison of imaging techniques
Regional LV function:
Dobutamine echocardiography had the highest positive predictive Curr Probl Cardiol 2001;26:141
value (P < 0:05 vs. others)
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37. Subset analysis of 18 studies including xxx pts have 2 kinds of viabilty
studies:
Nuclear imaging was more sensitive in the prediction of recovery of
function than dobutamine echocardiography, whereas dobutamine
echocardiography was more specific.
The pooled results showed a higher negative predictive value for nuclear
imaging (83% vs. 79%) and a higher positive predictive value for
dobutamine echocardiography (79% vs. 63%).
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38. Global LVEF improvement
How much hibernating myocardium must be present for an improvement in LVEF?
The threshold amount of hibernating myocardium necessary to classify a patient as
hibernating varies from a minimum of 8% to a maximum of 53% with a mean of 22%.
Only one study used ROC analysis to assess the minimum amount of hibernating
myocardium necessary to detect an improvement of global function, which was 25% (. J
Am Coll Cardiol 1999;34:163)
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39. Guiding Clinical Principles
• Evaluation for hibernation is more useful in cases of dyspnea than or
angina
• SPECT and echo have similar capabilties to evaluate for viable and
hibernating myocardium
• choice will depend upon availability and local expertise, and on
whether the clinical question requires a sensitive or a specific
technique for predicting recovery of segmental function.
• MRI can typically be reserved for further classificaiton after SPECT or
echo.
• Positron emission tomography can normally be reserved for when
clinical suspicion of viability or hibernation remains after other imaging
techniques have proved negative
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