Presentation on theme: "MYOCARDIAL STUNNING AND HIBERNATION"— Presentation transcript:
1MYOCARDIAL STUNNING AND HIBERNATION Dr Binjo J Vazhappilly.SR , Cardiology Dept.Calicut Medical College
2StunningDefinition :Prolonged and fully reversible dysfunction of the ischemic heart that persists despite the normalization of blood flow.
31st 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.
4Features of stunning Normal perfusion. Depressed myocardial function. Dissociation of usual relationship between subendocardial flow and function.Reversible .Function improves with inotropic agents.
7Stunning occurs in a wide variety of settings that differ from one another in several aspects At experimental level it can occur during1. Single , completely reversible episode ofregional ischemia (< 20 min )2. Multiple, completely reversible episodes ofregional ischemia3. Partly reversible plus partly irreversibleischemia in vivo ( > 20 min & < 3 hrs)
8After global ischemia in vitro (isolated heart preparations)5. After global ischemia in vivo (cardioplegic arrest)6. After exercise-induced ischemia
9Clinical Relevance In the clinical setting stunning can occur 1. Brief period of total coronary occlusion:pts with angina due to spasm2. Global ischemia after cardiopulmonary bypass.3. In combination : Subendocardium is infarcted andoverlying subepicardium reversibly injured in MI4. Following exercise in presence of a flow limitingstenosis5. Ischemic bout that is induced by PCI
10Mechanisms of Stunning There is no unified view of pathogenesis of stunningMost plausible hypotheses areOxyradical hypothesis : oxidant stress secondaryto the generation of ROS.Calcium hypothesis : results from disturbance ofcellular calcium homeostasis.
11Oxyradical Hypothesis Role of ROS in pathogenesis of stunning is provenIts role in all settings of stunning is unclearROS-mediated injury responsible for stunning occurs in initial moments of reperfusionAntioxidant therapies alleviate stunning whether begun before ischemia or just prior to reperfusionBut ineffective when begun after reperfusionNone of the antioxidant therapies completely prevented myocardial stunning
12Calcium hypothesisTransient 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.
15Term 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.
16Diamond et al. in 1978 1st used the word hibernation in ischemic dog myocardium. Its importance was recognized by Rahimtoola in early 1980s.
17Mechanisms 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 insustained depression of contractile function.
18Genomics of SurvivalMaintained 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.
24ASSESSMENT OF MYOCARDIAL VIABILITY ECG : gives little information.Dobutamine stress echocardiography.SPECT with thallium-201 or technetium-99 m.PETMRI
25Characteristics of dysfunctional but viable myocardium
26No 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.
27Dobutamine 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.
29Stress Echo Interpretation Rest / BaselineLow dose stressPeak & post stressNormalHyper dynamicIschemicNormal / severe ischemia – new RWMADecreasedScarWMANo changeHibernatingImprovedWorsensStunned
30Advantage of Echo based techniques Safety , low cost , widespread availability of equipment .DisadvantageSpatial resolution is relatively low.High interobserver variability.Diagnostic accuracy is reduced in pts with pooracoustic window.
31SPECTThallium-201Early 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.
32Technetium 99lipophilic 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.
33PETGlucose 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.
37Magnetic resonance imaging Three techniques are being used:1.Resting MRI to measure end diastolic wall thickness.2. Dobutamine MRI to evaluate contractile reserve3. Contrast enhanced MRI to detect extentand transmurality of scar tissue.
38Resting MRIEnd diastolic wall thickness < 6 mm representtransmural scar.Dobutamine MRIEvaluate contractile reserve.Increased resolution of MRI avoid subjectivevariation of echo.Has sensitivity of 89% & specificity of 94% to predict improvement after revascularization.
39Contrast enhanced MRIAllows precise detection of scar tissue.Extent & transmurality of scar can be assessed.Can detect subendocardial scar.Similar to FDG PET in detecting scar.
40Accuracy of non-invasive techniques to assess myocardial viability
41Impact 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.
42In 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.
43Treatment 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%).
45Summary Stunning and hibernation are 2 causes for LV dysfunction. Both conditions imply presence of viable myocardium and are reversible.
46References HURST’S THE HEART 13TH EDITION BRAUNWALD’S HEART DISEASE NINTH EDITIONMedical and Cellular Implications of Stunning, Hibernation, and Preconditioning :Circulation. 1998;97:Stunning, Hibernation and Assessment of Myocardial Viability : Circulation.2008;117:Molecular and Cellular Mechanisms of Myocardial Stunning :PHYSIOLOGICAL REVIEWS Vol. 79, No. 2, April 1999
47Hibernating Myocardium : PHYSIOLOGICAL REVIEWS Vol. 78, No Hibernating Myocardium : PHYSIOLOGICAL REVIEWS Vol. 78, No. 4, October 1998Clinical assessment of myocardial hibernation Heart 2005;91;