2. Stunning
• Definition :
Prolonged and fully reversible dysfunction of
the ischemic heart that persists despite the
normalization of blood flow.
3. • 1st described by Heyndrickx et al in 1975 in
conscious dogs undergoing brief coronary
occlusions.
• In that study regional contractile dysfunction
lasted for 6 hrs following 5 min and > 24 hrs
following 15 min of ischemia.
4. Features of stunning
• Normal perfusion.
• Depressed myocardial function.
• Dissociation of usual relationship between
subendocardial flow and function.
• Reversible .
• Function improves with inotropic agents.
7. • Stunning occurs in a wide variety of settings that
differ from one another in several aspects
• At experimental level it can occur during
1. Single , completely reversible episode of
regional ischemia (< 20 min )
2. Multiple, completely reversible episodes of
regional ischemia
3. Partly reversible plus partly irreversible
ischemia in vivo ( > 20 min & < 3 hrs)
8. 4. After global ischemia in vitro (isolated heart
preparations)
5. After global ischemia in vivo (cardioplegic arrest)
6. After exercise-induced ischemia
9. Clinical Relevance
• In the clinical setting stunning can occur
1. Brief period of total coronary occlusion:
pts with angina due to spasm
2. Global ischemia after cardiopulmonary bypass.
3. In combination : Subendocardium is infarcted and
overlying subepicardium reversibly injured in MI
4. Following exercise in presence of a flow limiting
stenosis
5. Ischemic bout that is induced by PCI
10. Mechanisms of Stunning
• There is no unified view of pathogenesis of stunning
• Most plausible hypotheses are
Oxyradical hypothesis : oxidant stress secondary
to the generation of ROS.
Calcium hypothesis : results from disturbance of
cellular calcium homeostasis.
11. Oxyradical Hypothesis
• Role of ROS in pathogenesis of stunning is proven
• Its role in all settings of stunning is unclear
• ROS-mediated injury responsible for stunning occurs
in initial moments of reperfusion
• Antioxidant therapies alleviate stunning whether
begun before ischemia or just prior to reperfusion
• But ineffective when begun after reperfusion
• None of the antioxidant therapies completely
prevented myocardial stunning
12. Calcium hypothesis
• Transient Ca2+ overload activates Ca2+-dependent
proteases which degrades and induces covalent
modifications of myofilaments.
• It results in ↓ responsiveness to Ca2+, manifested by
a decrease in maximal force of contraction.
15. • Term hibernation is borrowed from zoology and
implies an adaptive reduction of energy expenditure
through reduced activity in situation of reduced
energy supply.
• In CAD myocardial hibernation refers to adaptive
reduction of myocardial contractile function in
response to reduction of myocardial blood flow.
16. • Diamond et al. in 1978 1st used the word
hibernation in ischemic dog myocardium.
• Its importance was recognized by Rahimtoola in early
1980s.
17. Mechanisms of hibernation
• Smart heart hypothesis :
Myocardial metabolism and function are reduced to
match concomitant reduction in coronary blood flow
which prevents necrosis.
• Repetitive stunning hypothesis:
Repetitive episodes of ischemia results in
sustained depression of contractile function.
18. • Genomics of Survival
Maintained viability in hibernation suggests
possibility of genomic adaptation.
Major survival genes (antiapoptotic, cytoprotective
& growth-promoting genes) and their
corresponding proteins are up regulated in
hibernating myocardium.
22. Clinical Relevance
• 20 to 50 % of pts with chronic ischemic LV
dysfunction have significant amount of viable
hibernating myocardium.
• They improve with revascularization.
23.
24. ASSESSMENT OF MYOCARDIAL
VIABILITY
• ECG : gives little information.
• Dobutamine stress echocardiography.
• SPECT with thallium-201 or technetium-99 m.
• PET
• MRI
26. • ECG
No clear correlation between Q waves on ECG and
presence of viability.
Pts with preserved QT dispersion are likely to have
viable myocardium.
Pts with high QT dispersion have predominantly
non-viable scar tissue.
27. Dobutamine Stress Echocardiography
• Hypokinetic or akinetic regions improving during low
dose dobutamine infusion (5–10 µg/kg/min) is
indicative of viable tissue.
• At higher doses (upto 40 µg/kg/min plus atropine)
wall motion may improve or diminish, reflecting
inducible ischemia.
• Biphasic response is highly predictive of recovery of
function after revascularization.
28.
29. Stress Echo Interpretation
Interpretation Rest /
Baseline
Low dose stress Peak & post
stress
Normal Normal Normal Hyper dynamic
Ischemic Normal Normal / severe
ischemia – new
RWMA
Decreased
Scar WMA No change No change
Hibernating WMA Improved Worsens
Stunned WMA Improved Improved
30. • Advantage of Echo based techniques
Safety , low cost , widespread availability of
equipment .
• Disadvantage
Spatial resolution is relatively low.
High interobserver variability.
Diagnostic accuracy is reduced in pts with poor
acoustic window.
31. SPECT
• Thallium-201
Early uptake is proportional to regional blood
flow & delayed uptake indicates preserved
Na+ K+ pump and an intact cell membrane.
Defects on initial images that improve later
are viable.
32. • Technetium 99
lipophilic molecules and their intracellular
retention requires intact mitochondrial function.
Gating allow simultaneous assessment of
myocardial perfusion & contractile function.
• SPECT has higher sensitivity & lower specificity
than techniques based on contractile reserve.
33. PET
• Glucose utilization is evaluated with FDG and
regional perfusion assessed with N13-ammonia,
rubidium-82, or O15- labeled water.
• A normal perfusion and FDG uptake or reduced
perfusion with enhanced FDG uptake indicates viable
myocardium.
• Concordant reduction in FDG uptake and myocardial
perfusion is indicative of scar tissue.
• PET is regarded as gold standard for viability
assessment.
37. Magnetic resonance imaging
• Three techniques are being used:
1.Resting MRI to measure end diastolic wall
thickness.
2. Dobutamine MRI to evaluate contractile reserve
3. Contrast enhanced MRI to detect extent
and transmurality of scar tissue.
38. • Resting MRI
End diastolic wall thickness < 6 mm represent
transmural scar.
• Dobutamine MRI
Evaluate contractile reserve.
Increased resolution of MRI avoid subjective
variation of echo.
Has sensitivity of 89% & specificity of 94% to predict
improvement after revascularization.
39. • Contrast enhanced MRI
Allows precise detection of scar tissue.
Extent & transmurality of scar can be assessed.
Can detect subendocardial scar.
Similar to FDG PET in detecting scar.
41. Impact of Revascularization on LV Function
• Studies shows LV ejection fraction improves
significantly (ie ≥ 5%) after revascularization in 60%
of patients (range 38% to 88%).
• To predict 5% improvement in LVEF, at least 25% of
LV should be viable using DSE and ≈38% using
conventional nuclear medicine and PET.
42. • In dyskinetic and akinetic segments, absence of scar
or a transmural extension of scar of <25% have PPV
of 88% and NPV 89% for functional recovery.
43. Treatment and Survival Rates
• Meta-analysis that pooled data of 3,088 pts from 24
studies demonstrated improved survival after
revascularization in pts with hibernation.
• Revascularization resulted in 79.6% reduction in
mortality (16% vs 3.2%)
• In absence of hibernation, no significant difference
in mortality with revascularization (7.7% vs 6.2%).
44.
45. Summary
• Stunning and hibernation are 2 causes for LV
dysfunction.
• Both conditions imply presence of viable
myocardium and are reversible.
46. References
• HURST’S THE HEART 13TH EDITION
• BRAUNWALD’S HEART DISEASE NINTH EDITION
• Medical and Cellular Implications of Stunning,
Hibernation, and Preconditioning :Circulation.
1998;97:1848-1867
• Stunning, Hibernation and Assessment of Myocardial
Viability : Circulation.2008;117:103-114
• Molecular and Cellular Mechanisms of Myocardial
Stunning :PHYSIOLOGICAL REVIEWS Vol. 79, No. 2,
April 1999