Download - MYOCARDIAL STUNNING AND HIBERNATION
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MYOCARDIAL STUNNING AND HIBERNATION
Dr Binjo J Vazhappilly.SR , Cardiology Dept.
Calicut Medical College
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Stunning
• Definition : Prolonged and fully reversible dysfunction of
the ischemic heart that persists despite the normalization of blood flow.
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• 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.
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Features of stunning
• Normal perfusion.• Depressed myocardial function.• Dissociation of usual relationship between
subendocardial flow and function.• Reversible . • Function improves with inotropic agents.
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Brief total occlusion
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Prolonged partial occlusion
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• 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)
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4. After global ischemia in vitro (isolated heart preparations) 5. After global ischemia in vivo (cardioplegic arrest) 6. After exercise-induced ischemia
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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
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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.
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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
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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.
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Myocardial Hibernation
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• 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.
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• Diamond et al. in 1978 1st used the word hibernation in ischemic dog myocardium.
• Its importance was recognized by Rahimtoola in early 1980s.
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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.
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• 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.
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Natural history of hibernation
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Histological Features
• Myolysis• Glycogen accumulation• Increased interstitial fibrosis
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Clinical Relevance
• 20 to 50 % of pts with chronic ischemic LV dysfunction have significant amount of viable hibernating myocardium.
• They improve with revascularization.
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ASSESSMENT OF MYOCARDIAL VIABILITY
• ECG : gives little information.• Dobutamine stress echocardiography.• SPECT with thallium-201 or technetium-99 m.• PET • MRI
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Characteristics of dysfunctional but viable myocardium
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• 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.
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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.
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Stress Echo InterpretationInterpretation Rest /
BaselineLow dose stress Peak & post
stressNormal 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
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• 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.
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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.
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• 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.
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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.
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Hibernation in LAD occlusion
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FDG SPECT
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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.
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• 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.
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• 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.
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Accuracy of non-invasive techniques to assess myocardial viability
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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.
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• 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.
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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%).
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Summary• Stunning and hibernation are 2 causes for LV
dysfunction. • Both conditions imply presence of viable
myocardium and are reversible.
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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
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• Hibernating Myocardium : PHYSIOLOGICAL REVIEWS Vol. 78, No. 4, October 1998
• Clinical assessment of myocardial hibernation Heart 2005;91;111-117
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