1) Myocardial stunning and hibernation are forms of reversible left ventricular dysfunction that occur despite restored blood flow. Stunning results from brief ischemia while hibernation is an adaptive response to chronic reduced blood flow. 2) Techniques like dobutamine stress echocardiography, SPECT, PET, and MRI can assess myocardial viability and predict functional recovery after revascularization. The presence of viable tissue that improves contractility with inotropic stimulation or shows metabolic activity indicates potential benefit from revascularization. 3) Revascularization in patients with hibernating myocardium improves left ventricular ejection fraction and reduces mortality compared to medical therapy alone. At least 25% viability is needed to predict meaningful

1. MYOCARDIAL STUNNING AND
HIBERNATION
Dr Binjo J Vazhappilly.
SR , Cardiology Dept.
Calicut Medical College

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.

5. Brief total occlusion

6. Prolonged partial occlusion

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.

14. Myocardial Hibernation

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.

20. Natural history of hibernation

21. Histological Features
• Myolysis
• Glycogen accumulation
• Increased interstitial fibrosis

22. Clinical Relevance
• 20 to 50 % of pts with chronic ischemic LV
dysfunction have significant amount of viable
hibernating myocardium.
• They improve with revascularization.

24. ASSESSMENT OF MYOCARDIAL
VIABILITY
• ECG : gives little information.
• Dobutamine stress echocardiography.
• SPECT with thallium-201 or technetium-99 m.
• PET
• MRI

25. Characteristics of dysfunctional but
viable myocardium

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.

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.

34. Hibernation in LAD occlusion

35. FDG SPECT

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.

40. Accuracy of non-invasive techniques to
assess myocardial viability

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%).

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

47. • Hibernating Myocardium : PHYSIOLOGICAL
REVIEWS Vol. 78, No. 4, October 1998
• Clinical assessment of myocardial hibernation
Heart 2005;91;111-117

48. THANK YOU