Myocardial Viabilty assessment

1. Assessment of myocardial
viability

2. • Viability
– Dysfunctional myocardium subtended by diseased
coronary arteries
– Limited or absent scarring
– Potential for functional recovery
• Prospective definition
• Reversible ischemic contractile dysfunction
– Myocardial stunning
– Myocardial hibernation

3. Myocardial stunning
• Heyndrickx et al 1978
• Prolonged and fully reversible contractile dysfunction
of the ischemic heart that persists after reperfusion
• Transient period of ischemia f/b reperfusion-depressed
function at rest,preserved perfusion
• Affected area responsive to inotropes
• Time course not altered by use of inotropes-
spontaneously resolve within a week
• Duration of stunning depends on the duration and
severity of ischemia and the adequacy of arterial flow

4. Clinical relevance
• Exercise induced ischemia
• Acute coronary syndrome
• Angioplasty-balloon inflation
• Cardiopulmonary bypass

5. Mechanism
• Calcium hypothesis-decrease responsiveness
to calcium
• Oxy radical hypothesis-ROS during reperfusion
impairs calcium handling

6. Myocardial hibernation
• Diamond et al 1978
• Persistent LV contractile dysfunction when
myocardial perfusion is chronically reduced but
sufficient to maintain viability of tissue
• Depressed function and perfusion at rest
• Progressively reversible after revascularisation
• Time to restoration-
– Months to one year
– Depend on duration and severity of flow
reduction&ultrastructural changes

7. Mechanisms
• Smart heart hypothesis
– Myocardial function &metabolism reduced to
match a reduction in blood flow
• Repetitive stunning hypothesis
– Repetitive episodes of ischemia reperfusion from
supply demand mismatch leading to sustained
depression of contractile function

8. Cellular mechanisms
• Apoptosis prominent during transition to
hibernation-30%cell loss
• Compensatory regional myocyte hypertrophy-to
maintain normal wall thickness
• Increase in interstitial connective
tissue,myolysis,increased glycogen
deposition,minimitochondria
• Cell survival programme-downregulation of
glycogen synthase kinase,increase anti apoptotic
proteins
• Downregulation of beta adrenergic adenylyl
cyclase

9. Clinical assessment
• Heart failure and active angina
– Directly angiography
– Viability study may have a role in planning
revascularisation strategy once coronary anatomy
known
• Heart failure and no angina
– Class 1 recommendation for assessment of
viability in pts with CAD and LVD
– Class 2a rec.for assessment of co-presence of CAD

10. • STEMI
– Class2a rec. for viability assessment 4 to 10 days
after STEMI in hemodynamically&electrically
stable pts.to define potential effect of
revascularisation

11. • Strong association b/w myocardial viability
and improved survival after revascularization
in pts with chronic CAD and LV dysfunction.
– Allmann KC et al;JACC 2002
• Pts with viability-revascularization a/w 79%
reduction in mortality (16% vs. 3.2%) as
compared to conserv.Rx
• Pts without viability-no significant difference
in revasc. Vs medical therapy (7.7% vs. 6.2%)

14. • In patients with ischemic cardiomyopathy 55%
had viable myocardium by PET&27% had
improved LVEF after revascularisation
– Auerbach MA et al;circulation 1999

16. Techniques for assessment of viability
• Myocardial glucose utilisation-PET FDG
• Cell membrane integrity-SPECT Thallium
• Intact mitochondria-SPECT Tc
• Contractile reserve-dob.echo and dob.MRI
• Scar tissue-DEMRI,MSCT

17. Echocardiographic assessment
• LV end-diastolic wall thicknesses
– Less than 6 mm-less likely to be viable

18. Dobutamine stress echo
• Low-dose dobutamine (5–10 μg/kg/min)
– Increase contractility in viable myocardium
• High-dose dobutamine(upto 40 μg/kg/min)
– Biphasic response –initial improvement F/B worsening –
underperfused but viable tissue-most specific sign of
improvement after revasc.
– Uniphasic response-sustained improvement-myocardial damage
with subsequent reperfusion-less predictive of improvement
after revasc.
– Deterioration of wall motion without initial improvement-severe
ischemia
– No change in wall motion-scar
• Sensitivity(84%),specificity(81%)for recovery of function

19. • Strengths-
– Higher specificity
– Viability&ischemia assessed
– MR can be detected
– Good spatial resolution
– Widely available
– Lower cost
– Predictive of clinical outcomes

20. • Limitations
– Poor window in 30%
– Lower sensitivity
– Viable regions with absent flow reserve will not
show thickening
– Reliance on visual assessment

21. Myocardial contrast echo
• Gas-filled microbubbles <7 μ as contrast agents
• Produces myocardial opacification and facilitates
identification of LV borders
• Burst of high-intensity ultrasound-destroy
microbubbles within the myocardium-
replenishment observed over the next 10 to 15
cardiac cycles
• Viable if homogeneous contrast intensity
• Absence of contrast enhancement-nonviable
myocardium

23. • Sensitivity 89% and specificity of 51%
• Higher sensitivity,lower specificity compared
to DSE

24. • Strengths
– Microcirculatory integrity
– Extent of viability
– Precise deleination
– Viability assessed in total occlusion
• Limitation
– Poor window
– Scant clinical data

25. Myocardial strain rate imaging
• Determination of velocities in two segments
of myocardium separated by a distance
• Strain rate is rate of change of velocity b/w
these points
• Increased sensitivity from 73% to 83%
compared to visual assessment

26. Echo based techniques
• Strengths
– Safety, portability, low cost,widespread availability
of equipment
– Absence of radiation hazard
• Limitations
– Operator dependent
– Spatial resolution is relatively low
– Diagnostic accuracy reduced in poor acoustic
window

27. TMT
• Exercise induced ST elevation in infarct related
area was associated with residual tissue
viability
– Margonoto et al ;JACC 1995
• Sensitivity&specificity of reciprocal ST-
segment depression a/w exercise-induced ST-
segment elevation in prior Q wave infarct for
detecting residual viability-84%&100%
– Nakano A et al;JACC 1999

28. SPECT-Th-201
• K+ analogue utilizes active cellular transport
system-relies on intact cell
• Uptake depends on viability &regional perfusion
• Redistribution-gradual accumulation of tracer in
hypoperfused areas,rapid washout from normally
perfused areas
• Segments with tracer uptake >60%-viable
• Subendocardial scar tissue may be labelled as
viable-lower specificity

29. • Rest redistribution protocols-
– Defects in initial images that improve in 4 hour
image-viable myocardium
– Additional 24 hr image if fixed defects in 4 hr
image
– S/L NTG prior to injection
– Less sensitive-86%,specificity 47%

30. Rest redistribution thallium-defect in inferoseptal wall that redistributes

31. • Stress redistribution protocol
– Pharmac.or exercise stress
– Th inj. &imaging f/b 4 hr image
– Myocardium not perfused with rest or stress-scar
– Defect on stress and improves on rest-ischemic
&viable
– 24 hr image for late redistribution

32. • Stress redistribution reinjection protocols
– Reinjection of Th201 and image repeated 24hr
later
– Viable myocadium-uptake of tracer on reinjection
in segments with no uptake on stress
– Scar –defect that persists
– Sensitivity 90% specificity 54%

33. Tc99m labelled agents
• Rely on sarcolemmal integrity and mitochondrial
function
• Short half life,higher doses,better image
• Redisribution less-less helpful in assessing
viability
• Tc NOET-similar redistribution kinetics to
Thallium
• Viability criterion is>50% tracer uptake in
dysfunctional segments.

34. Ant
Inf
LatSep
Apex  Base
Ant
Inf
Apex
Septum  Lateral
Apex
Sep Lat
Inferior  Anterior
Stress
Stress
Stress
Rest
Rest
Rest
Reversible Ischeamia, defect appears
at stress and disappears during rest

35. Ant
Inf
LatSep
Apex  Base
Ant
Inf
Apex
Septum  Lateral
Apex
Sep Lat
Inferior  Anterior
Stress
Stress
Stress
Rest
Rest
Rest
Fixed Scar, defect is seen in both stress and rest

36. • Strengths
– High sensitvity
– Quantitative objective criteria
– LVEF
– FDG with special collimator
– Predictive of outcomes

37. • Limitations
– Reduced spatial resolution &sensitivity compared
to PET
– Attenuation artefacts
– Cannot differentiate endocardial viability
– Less quantitative than PET

38. SPECT FDG
• High energy collimators to detect regional FDG
uptake by SPECT camera.
• Concordance between 18FDG SPECT and
18FDG PET was 95%
• Sensitivity of 88% and specificity of 73% as
compared to PET
– Srinivasan G et al;circulation 1998
• Increases sensitivity to detect viability
compared to Thallium

39. PET
• Positron emitting isotopes releasing 2 photons at
angle180,detected by camera by coincidence
counting to give a higher resolution
• Perfusion tracers-N13 ammonia,Rb 82,O15 water
• Metabolic tracers- F18DG,C11acetate,C11
palmitate
• FDG taken up by viable
cells,phoshorylated&trapped inside
• Poor uptake in diabetics

40. Interpretation
• Normal perfusion-viability
• Flow metabolism mismatch-reduced perfusion
with intact metabolism-hibernating viable
myocardium
• Flow metabolism match-impaired FDG uptake
with reduced perfusion-scar
• Gold standard for assessment of viability

42. Perfusion metabolism mismatch-apex,anterior
anterolateral wall

43. • Strengths-
– Perfusion &metabolism
– More sensitive
– No attenuation
– Absolute blood flow can be measured
– Predictive of outcomes

44. • Limitations
– Lower specificity to dob.echo&MRI
– Cannot differentiate b/w endocardial and
epicardial viability
– High cost
– Limited availability

45. Cardiac MRI
• Preserved wall thickness >5.5mm correlated with
PET viability(sen.95%,spe.41%)
– Baer FM et al;circulation 1995
• Dobutamine cine MRI
– Improved thickening>2mm by low dose dobutamine
CMR(sen. 73%,spe.83%)
– Higher accuracy than dobutamine echo
– Monitoring difficult
• Delayed enhancement MRI(DEMRI)
– Sen.95%,spe.45%

46. • DEMRI using Gadolinium based agents (i.v.0.2
mmol/kg)
• Extracellular space
• Infarcted or scarred tissue-interstitial spaces
larger-delayed wash in &delayed wash out
• Hyperenhanced area of myocardium on
images taken 10 to 20 min after contrast
• Size and shape of infarct correlate with
histology

49. • Scarring begins at subendocardial surface and
extends toward epicardium
• Transmural extent of infarct used to determine
viability of each segment
• Likelihood of functional improvement
inversely related to TEI
• 78%with no hyperenhancement
improved,only 2% with >75% TEI improved
– Kim RJ et al;NEJM 2000

56. • Mean TEI 10%-Improved contractility after
revasc.
• Mean TEI 41%-no improvement in contractility

57. • Nuclear scintigraphy-% of viability in a given
segment is assessed indirectly
• DEMRI-direct assessment of viability in a given
segment

59. • Indirect method show only 39% viability,direct
method gives 70% viability-proven by
revascularisation
• Mean transmural extent predicted
irreversibility-41% by MRI,35% by histology
• DEMRI superior sensitivity&specificity to
SPECT;similar sensitivity and superior
specificity to PET

60. • Strengths
– Accurate assessment of extent of scar
– Superior spatial resolution
– Wall thickness correctly measired
– Simultaneous assessment of perfusion,function
and viability
– Good imaging windows

61. • Limitations
– High cost
– Limited availability
– Longer time
– Contra.with implanted ferromagnetic objects
– Gadolinium contra.in CKD with GFR<30ml/min
– Claustrophobia
– Irregular rhythems
– Breathholding required

62. MSCT
• Iodinated contrast agents accumulate in
infarcted myocardium similar to DEMRI
• High spatial resolution-differentiation of
transmural &subendocardial infarction
possible
• Old infarctions have lower CT densities
compared to recent infarcts
• Good agreement b/w DEMRI and late
enhancement of MSCT

63. subendocardial hyperenhancement of the posterior wall

64. 64-Slice Computed Tomography hyperenhancement of the inferior wall

65. • Sensitivity&specificity -92%& 100%
respectively to detect viability in acute
myocardial infarction
• Presence of viable segments in an AMI
identified when hyperenhancement is absent
or involves <50% of the myocardial wall
thickness
• Advantages
– Shorter imaging time
– widely available

66. Extent of viability
• Magnitude of improvement depends on
quantitative extent of myocardial viability
• 25% of the LV should be viable by DSE&38%
by nuclear imaging

67. Comparison of different techniques
• Baer FM ,European heart journal 2000
– Higher accuracy for dob.TEE and dob.MRI for
predicting improvement in LV function post
revasc.

69. Comparison-DSE,MCE,SPECT
shimoni et al;circulation2003

70. • PET and SPECT have higher sensitivity &DSE
has higher specificity for assessing viability
– Robert Bonow;JACC 2002
• Magnitude of improvement in outcome with
revascularization did not differ whether
assessed by PET,SPECT or DSE

73. DEMRI vs PET
KLEIN et al;circulation 2002

74. DSE Vs nuclear imaging
• Sensitivity 90% for nuclear imaging,74% for
DSE
• Specificity 57% for nuclear imaging,78% for
DSE
– Bax JJ et al;2002
• Integration of both may be useful

75. Survival benefit