Imaging techniques for myocardial hibernation


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Imaging techniques for myocardial hibernation

  1. 1. Imaging techniques for the Assessment of Myocardial Hibernation Michael G. Katz, MD Fellow in Cardiovascular Disease Instructor in Psychiatry October 20, 2011
  2. 2. • CAD is the primary cause of decreased LVEF• Drugs such as ACEis, ARBs, BB, and aldosterone antagonists have improved the prognosis of heart failure, but the outcome with medical treatment remains poor.• Until recently, there was no data from multicentre trials assessing the value of revascularization procedures for the relief of HF symptoms. • However, single-centre, observational studies on HF of ischemic origin suggest that revascularization may lead to symptomatic improvement and potentially improve cardiac function. • CASS registry • mortality of patients with LV dysfunction increased rapidly with reduction in LVEF, and that one-year mortality was reduced from 24% on medical therapy to 15% after revascularisation in patients with LVEF below 25% Circulation 2006;114:1202 Curr Opin Cardiol 2008;23:148 2
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  6. 6. "The take-home message for me is that the STICH trial supports bypasssurgery on top of best medical therapy vs medical therapy alone toreduce cardiovascular morbidity and mortality and that many patientswho are now treated for heart failure without ever being assessed for thepotential of having angiographic coronary disease should be evaluated forthat, because [coronary disease] does not present the same way in everypatient,” […] "Heart failure without angina shouldnt excludepatients from an angiographic evaluation." 7
  7. 7. General considerations• perioperative mortality in patients with left ventricular dysfunction is relatively high• it is important to revascularise only patients who will obtain overall benefit• When angina is a dominant symptom, the decision is relatively simple• When symptoms of left ventricular dysfunction dominate, the decision is more difficult because it is harder to distinguish between permanent left ventricular dysfunction and dysfunction that might improve after treatment. 8
  8. 8. • Common causes of ischemic LV dysfunction are: • full-thickness myocardial infarction • partial thickness infarction • myocardial stunning, and • myocardial hibernation• Complicated by the potential coexistence of different states in the same patient or even in the same myocardial region.• Imaging techniques can detect and assess • myocardial viability, • metabolism, • perfusion, and • FunctionMultiple techniques to assess the above, but most hospitals either donot have access to them all or lack expertise in some of them. 9
  9. 9. Definitions 10
  10. 10. Viable “myocardial cells that are alive and hence also the myocardium that they constitute.” Although individual myocytes may be viable or non-viable, CLINCALLY, the myocytes exist within the macroscopic myocardium Partially Viable Nonviable Fully Viable Partial-thickness infarction Scarred Full-thickness infarction No remaining myocytesThe term “viable” implies nothing with regard to contractile state.Viable myocardium may contract normally or it may be dysfunctional, de- pending on other circumstances. 11
  11. 11. StunnedContractile dysfunction of viable myocardium caused by abrief period of ischemia followed by restoration of perfusion• ? free radicals and a transitory overload of calcium• Examples: • Myocardial infarction that is aborted by thrombolysis • After an episode of unstable angina • After ischemia induced by exercise testing• Dysfunction may persist from an hour to several days, but function ultimately returns to normal if normal perfusion is maintained 12
  12. 12. Hibernating (the most difficult to understand) A state of contractile dysfunction in viable myocardium, but in the setting of chronic ischemic heart disease • hibernating myocardium requires an intervention such as revascularisation for recovery • ALTHOUGH: medical therapy might also be effective in relieving hibernation by abolishing ischemia. You don’t know if myocardium is hibernating or just dead until tissue is Retrospective definition revascularized… But most surgeons or interventionalists won’t revasc unless they know tissue is hibernating. 13
  13. 13. Prospective definition of hibernationOne definition: “viable and dysfunctional myocardium” Partially Viable Nonviable Fully Viable Partial-thickness infarction Scarred Full-thickness infarction No remaining myocytesHowever, not all viable myocardium may contract… it may betethered to infarcted tissue. 14
  14. 14. • The demonstration of inducible ischemia in the relevant section of myocardium is a helpful addition to the definition since hibernation is an ischemic syndrome• It is unlikely to be present in the absence of inducible ischemia.• Thus, the most useful surrogate definition of hibernation is viable and dysfunctional myocardium in which impaired perfusion reserve leads to inducible ischemia. 15
  15. 15. Pathophysiological definition on hibernationHibernation was originally defined as “a state of persistently impairedmyocardial and left ventricular function at rest due to reduced coronaryblood flow that can be partially or completely restored to normal if themyocardial oxygen supply/demand ratio is favourably altered.”• It is still controversial whether or not perfusion is reduced at rest• Although, we know that it is not always reduced.• Therefore perfusion is usually omitted from the definition of hibernation. 16
  16. 16. Prevalance of recoverable function? J Am Coll Cardiol 1996;28:948Recovery is seen, on average, in 55–60% of dysfunctionalsegments, even in patients with baseline ejection fraction below40%May be an underestimate: 1) completeness of revasc is rarelyassessed and 2) tissue may take up to a year to recover. 17
  17. 17. EKGQ waves – NOT helpful• no relationship between the presence and extent of Q waves after myocardial infarction and infarct size assessed by myocardial perfusion imaging• 60% of regions with Q waves have viable myocardium detected by imaging techniques• QR complexes DO NOT contain more viable tissue than QS complexes• No correlation with QRS scoring and LVEF Circulation 1986;73:951 Am J Cardiol 2002;89:1171 Am Heart J 2002;144:865 Heart 1999;82:663 Ann Intern Med 1991;114:264 18
  18. 18. ST segment – Somewhat helpful • ST-segment elevation at rest in leads with Q waves is associated with more severe wall-motion abnormalities, less contractile reserve and greater end-systolic volume • extreme case, this is seen as ST elevation of aneurysm formation • ST elevation developing during exercise is a marker of maintained viability, and late improvement in LV function after myocardial infarction is more common when the ST segment is elevated during dobutamine echocardiography. • Inducible perfusion abnormalities assessed by SPECT have been seen in 94% of patients with exercise-induced ST elevation and in 50% with pseudonormalisation of the T wave but without ST elevation. • The combination of ST elevation and reciprocal ST depression increases the accuracy for detection of viable myocardium • ST elevation during exercise predicts FDG uptake with a sensitivity of 82% and specificity of 100% • functional recovery data re: exercise ST elevation is contradictory Heart 1997;77:115 Am J Cardiol 1998;82:148–53. Am Heart J 1999;137:500 Am J Cardiol 1998;81:12–6. J Am Coll Cardiol 1996;27:599 Am J Cardiol 1999;84:535–9. J Am Coll Cardiol 1992;19:948 Eur Heart J 2000;21:446 J Am Coll Cardiol 1995;25:1032 J Am Coll Cardiol 1999;33:620 19
  19. 19. T waves – NOT useful• Dobutamine-induced T-wave changes are associated with greater wall- motion abnormalities at rest and during stress, but the finding is not sufficiently accurate to predict residual myocardial viability after infarction (Am J Cardiol 1999;84:535)QT dispersion (maximum QT interval minus minimum QT interval)– Useful• After infarction, low QT dispersion is a marker of residual viable myocardium (Eur Heart J 2000;21:446)• QT dispersion of less than 70 ms has a sensitivity of 85% and a specificity of 82% for predicting FDG uptake in the region of infarction, and 83% and 71%, respectively, for predicting functional recovery after revascularization (Circulation 1997;96:3913). 20
  20. 20. Positron emission tomographyNot only can the distribution of molecules be imaged, but their uptakecan be quantifiedIt is possible to assess: • myocardial perfusion • glucose utilization • fatty acid up-take and oxidation • oxygen consumption • Contractile function, and • presynaptic and postsynaptic neuronal activity 21
  21. 21. FDG and ammonia F-fluoro-2-deoxy-DD-glucose (FDG) is a glucose analogue that is taken18up by viable cardiac myocytes in the same way as glucose, but itssubsequent metabolism is blocked and it remains within the myocyte • tracer of exogenous glucose uptake and, by inference, of myocardial viability N-ammonia is a perfusion tracer that is avidly extracted and retained in13viable myocytes by incorporation into glutamine 22
  22. 22. FDG and ammonia studies have most commonly been combinedbecause the relationship between glucose metabolism and perfusiondiffers in the different types of myocardium: Myocardium FDG Ammonia Stunned Nl Nl Hibernating Nl or Infarcted 23
  23. 23. It is not clear why the pattern of “perfusion-metabolism mismatch” is socharacteristic of hibernating. • uncertain whether the dominant feature is reduction of ammonia uptake or increase in FDG uptake, or a mixture of both Image analysis is often qualitative and based upon relative regional comparisons of uptake. The semiquantitative approach normalises FDG uptake to the segment with maximum ammonia uptake (presumed to be normal myocardium), which allows above-normal uptake of FDG uptake to be assessed. 24
  24. 24. Hybrid imaging• Even when a PET camera is available, imaging may be restricted to FDG because the half-lives of 13N and 15O are too short to allow ammonia and water imaging without an on-site cyclotron.• FDG imaging for myocardial viability has been combined with single photon perfusion tracers, such as thallium and MIBI. 25
  25. 25. Single-photon emission computed tomographyThallium-201• Thallium has been used extensively for identifying myocardial viability and hibernation; it was the first tracer to be used for this purpose • potassium analogue and myocardial uptake depends upon regional flow and upon an intact sarcolemmal membrane to facilitate transport • information on both perfusion and cell viability • Unfavorable properties: • Low-energy X-ray emission • Long half-life • appreciable radiation exposure to patients 26
  26. 26. Late-redistribution imaging shows increased uptake in up to 54% ofdefects that are fixed 4 h after stress injection.Reinjection leads to increased uptake in 49% of segments and ninestudies using this technique had positive and negative predictiveaccuracies of 69% and 89%, respectively, for improvement offunction after revascularisation. N Engl J Med 1990;66:394 Am J Cardiol 1995;75:17A Circulation 1996;94:2674
  27. 27. Technetium-99mMost widely reported technetium agent is Tc-99m-2 methoxyisobutylisonitrile (MIBI).Advantages over thallium • such as a shorter half-life with lower radiation exposure to the patient, a higher- energy gamma emission that reduces soft-tissue attenuation, and the potential for ECG-gated acquisitionDisadvantages • since uptake depends on both perfusion and viability, and viability may be underestimated in areas with reduced perfusion at rest. • In contrast, thallium uptake is independent of perfusion once redistribution is complete.Some studies have found MIBI to be inferior to thallium for identifying viability, butothers have found the two to be comparable (European Heart Journal 2004:25; 815) 28
  28. 28. ECG-gated SPECTAlthough the SPECT images are not high resolution, it is possible toassess myocardial thickening, as well as motion, since myocardial countsare linearly related to myocardial thickness.Thickening is a better assessment of regional function thanmotion. • infarcted regions can appear to move if dragged by neighboring normal regions, and normal regions can appear akinetic if regional motion is opposed by translation of the whole heart. 29
  29. 29. Stress Echo• Stress echocardiography allows inducible myocardial ischemia to be detected indirectly by direct visualization of the left ventricular dysfunction.• Normally performed on cessation of exercise and within 2 min because exercise-induced abnormalities are normally transitory.• In patients who are unable to exercise, dobutamine and dipyridamole are alternatives, but dobutamine is generally preferred • more readily induces ischaemia 30
  30. 30. Myocardial infarction, particularly transmural infarction, leads to thinned andakinetic segments at rest. However, if the function of an akineticsegment improves with stress, this implies the presence of viablemyocardium. • Low doses of dobutamine (5 lg/kg/min) are normally sufficient to provoke this response • If there is also inducible ischemia, then a biphasic response is • seen with initial improvement in function and deterioration at higher doses. • The extent of myocardial hibernation determined in this way predicts outcome after revascularisation. • The reported accuracy of stress echocardiography for predicting recovery of segmental function after revascularisation varies, with sensitivities of 70% to 85% and specificities of 80% to 90%. J Am Coll Cardiol 1999;33:1848 Am J Cardiol 1998;82:1339 Circulation 1999;100:141 Eur Heart J 2000;13:1091 31
  31. 31. MRIProvides information regarding: • anatomy, • function, and • blood flowLimitations: • including its temporal resolution, • the need for breath-holding with some acquisition sequences, and • difficulties with claustrophobic patients and pts with pacemakersTwo different approaches to the assessment of patients with chronic ischaemicLV fx: 1.Assess myocardial morphology, function at rest, and contractile reserve during pharmacological stress. 2.Image myocardial infarction and evaluate the microcirculation using paramagnetic contrast agents. 32
  32. 32. Myocardial thickness and contractile reserveHigh-resolution and high-contrast images, MRI is now the standardagainst which other techniques are compared for the measurement ofventricular volumes, ejection fraction, myocardial mass, and regional wallmotion. • Spatial resolution is 1–2 mm and temporal resolution is between 20 and 50 ms.Infarcts more than four months-old may become akinetic and thinned.Oldinfarctions with an end-diastolic myocardial thickness of less than 5.5mm have significantly reduced FDG uptake and this has been used as thethreshold for clinically significant myocardial viability 33
  33. 33. • 94% sensitivity but 52% specificity for predicting recovery of regional function 3 months after revascularisation.• segments of less than 5.5 mm in thickness are not very likely to be hibernating• segments of more than 5.5 mm in thickness may be hibernating or may simply consist of partial-thickness infarction Am Heart J 1939;18:647 Circulation 1995;91:1006 J Am Coll Cardiol1998;31:1040 34
  34. 34. Contractile reserve – Doubutamine stress MRIEssentially similar concept as doubutamine stress echoSensitivity of 89% and specificity of 94% for detecting hibernation.In a direct comparison between dobutamine MRI and SPECT in patientswith ischemic LV dysfunction undergoing revascularisation, MRI had a lowsensitivity (50%) but high specificity (81%), whereas the nuclearechniques were more sensitive, but less specific for predicting recovery ofregional function. (Circulation 1998;98:1869) 35
  35. 35. Contrast/ Perfusion MRIExtracellular paramagnetic contrast agents, such as gadolinium• exchange rapidly between the intravascular and extracellular interstitial space, but they do not pass through the intact membranes of cardiac myocytes so they are not direct markers of viability• used to detect regional abnormalities of myocardial perfusion• mechanism of late enhancement is not clear, but it is possibly related to an increase of the extra-cellular matrix late after infarction 36
  36. 36. Comparison of imaging techniquesRegional LV function: Dobutamine echocardiography had the highest positive predictive Curr Probl Cardiol 2001;26:141 value (P < 0:05 vs. others) 37
  37. 37. Subset analysis of 18 studies including xxx pts have 2 kinds of viabiltystudies:Nuclear imaging was more sensitive in the prediction of recovery offunction than dobutamine echocardiography, whereas dobutamineechocardiography was more specific.The pooled results showed a higher negative predictive value for nuclearimaging (83% vs. 79%) and a higher positive predictive value fordobutamine echocardiography (79% vs. 63%). 38
  38. 38. Global LVEF improvementHow much hibernating myocardium must be present for an improvement in LVEF?The threshold amount of hibernating myocardium necessary to classify a patient ashibernating varies from a minimum of 8% to a maximum of 53% with a mean of 22%.Only one study used ROC analysis to assess the minimum amount of hibernatingmyocardium necessary to detect an improvement of global function, which was 25% (. JAm Coll Cardiol 1999;34:163) 39
  39. 39. Guiding Clinical Principles• Evaluation for hibernation is more useful in cases of dyspnea than or angina• SPECT and echo have similar capabilties to evaluate for viable and hibernating myocardium • choice will depend upon availability and local expertise, and on whether the clinical question requires a sensitive or a specific technique for predicting recovery of segmental function.• MRI can typically be reserved for further classificaiton after SPECT or echo.• Positron emission tomography can normally be reserved for when clinical suspicion of viability or hibernation remains after other imaging techniques have proved negative 40
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