Determination of myocardial viability


 * Definitions:
 * Viable myocardium: an area of the heart with contractile dysfunction that improves after revascularization.
 * Viable myocardium can be:
 * Stunned: contractile dysfunction in the presence of normal blood flow. This is presumably cuased by inadequate flow reserve that results in repeated ischemic insult to the myocardium during periods of heightened stress.
 * Hibernating: contractile dysfunction with abnormal resting blood flow.
 * The myocardium may progress from being stunned to entering hibernation over time.


 * Indication for viability assessment:
 * Patients with
 * coronary artery disease and severe regional or global dysfunction
 * symptoms (heart failure and/or angina) that may improve after revascularization.
 * the ability to tolerate the revascularization procedure


 * Common radioisotopes used to assess myocardial viability:
 * Thallium- 201
 * Technetium 99m sestamibi
 * N13 ammonia or Rb82 with F18 FDG


 * Thallium- 201
 * Features that allow assessment of viability:
 * Potassium analog. Enters the mycardium via transport wit the Na/K ATPase.  Relies on cell membrane integrity for myocardial uptake.
 * Demonstrates redistribution- area of viable but severely ischemic myocardium may show increased tracer uptake over time.
 * Commonly used protocols to assess viability of a fixed perfusion defect found on stress testing:
 * Rest-distribution:
 * usually done on a separate date from the stress test.
 * inject 2-3mCi of thallium-201 at rest
 * acquire a "rest scan" within 10 minutes of tracer injection
 * acquire a "redistribution scan" after 4 hours
 * Stress-reinjection-delayed redistribution:
 * usually done immediately after the stress test.
 * re-inject 1 mCi of thallium after the "redistribtuion scan" (part of the stress test) was acquired 4 hours after exercise or adenosine/dobutamine injection.
 * acqure the "delayed redistribtuion scan" 24 hours after.
 * Commonly accepted criteria of viability:
 * >50%-75% uptake of the tracer in the segment of interest compared to the brightest segment
 * > 10% redistribution in the segment of interest
 * Data:
 * Rest-redistribution method:
 * Meta-analysis that pooled 22 small studies (14-46 patients) with a total of 557 patients shows that the presence of viability predicts segmental functional recovery with mean sensitivity of 86%, specificity of 59%, PPV of 69%, and NPP of 80%. (1)
 * Stress- reinjection- delayed redistribution method:
 * Meta-analysis that pooled 11 small studies (12-73 patients) with a total of 301 patients shows that the presence of viability predicts segmental function recovery with a mean sensitivity of 88%, specificity of 50%, PPV of 57%, and NPP of 83%. (1)
 * Few studies are done to evaluate whether the presence of viable myocardium with thallium imaging predict better prognosis after revascularization. One such study investigated 70 patients with multivessel disease with depressed ejection fraction (<40%) who underwent CABG.  Those with an above medium score of viable tissue has lower mortality (percentage find on powerpoint) 3 years after revascularization compared to others in the cohort. (2)


 * Technecium 99m Sestamibi
 * Feature that allows assessment of viability:
 * lipophlic cationic compound that relies on intact electrochemical gradient across the mitochondrial membrane for uptake into the myocardium.
 * Protocols to assess viability:
 * obtain a rest scan (either alone or as part of a stress test) and analyze the percentage of uptake in a particular segment compare to the brightest segment.
 * nitrate enhanced protocol:
 * administer intravenous nitrate for 20 minutes and inject the tracer when SBP dropped >20mmHg or SBP is <90. If none of these two criteria were met, the tracer was injected 15 minutes after the start of the infusion.  Compare the imaged acquire during nitrate infusion with the image obtained at rest.  The two scans are separated by 24 hours
 * Commonly accepted criteria of viability:
 * >50%-75% tracer uptake in the segment of interest compared to the brightest segment
 * >10% increase in tracer uptake in the nitrate-enhanced scan compared to the rest scan
 * Data:
 * Meta-analysis that pooled 20 small studies (14-50 patients), 7 of which used the nitrate- enhanced protocol with a total of 488 patients shows that the presence of viability predicts segmental functional recovery with a sensitivity of 81%, specificity of 66%, PPV of 71%, and NPP of 77% (1).
 * -	One study address whether the presence of viability by Tc 99m sestamibi imaging predicts better prognosis after revascularization. 105 patients with chronic CAD and LV dysfunction underwent nitrate-enhanced sestamibi imaging.  Amongst patients who received revascularization, the amount of viable tissue is the strongest independent predictor of event free (no MI) survival during a mean follow up of approximately 2 years with a relative risk of 1.4 (3)


 * Comparison with low dose dobutamine echocardiography:
 * Meta-analysis which pooled 18 small studies that directly compared viability assessment via a nuclear technique and low dose dobutamine echocardiography with a total number of 563 patients (15 studies used thallium 201, 3 studies used F18 FDG PET) indicates that nuclear techniques have higher sensitivity (88% vs 76%), lower specificity (53% vs 81%), lower PPV (75% vs 84%) and higher negative predictive value (80%vs 69%) for predicting segmental functional improvement (1)


 * Problems with current data regarding viability assessment:
 * Treatment (medical therapy vs. revascularization) was not randomized in any of the studies. Hence, outcomes are subject to referral bias.
 * Endpoints assessed in the majority of the trials focuses on functional improvement of particular myocardial segments after revascularization rather than more relevant endpoints such decreased morbidity and/or mortality.
 * Many of the studies are small. Meta-analysis assessing a particular method often pool together studies with varying methodologies; this makes the interpretation of the results difficult.


 * Conclusion:
 * Thallium 201 and Tc 99m Sestamibi imaging can both be used to assess viability of fixed perfusion defect found on stress testing.
 * Diagnostic performance of the two tracers is comparable for predicting segmental functional recovery
 * Compared to low-dose dobutamine echocardiography, nuclear assessment of cardiac viability predicts segmental functional recovery with higher sensitivity but lower specificity

References:
 * 1.Bax JJ, Poldermans D, Elhendy A, Boersma E, Rahimtoola SH. Sensitivity, specificity, and predictive accuracies of various noninvasive techniques for detecting hibernating myocardium. Curr Probl Cardiol. 2001;26:142–186.
 * 2.Pagley PR, Beller GA, Watson DD, Gimple LW, Ragosta M. Improved outcome after coronary bypass surgery in patients with ischemic cardiomyopathy and residual myocardial viability. Circulation. 1997;96:793–800
 * 3.Sciagra R, Pellegri M, Pupi A, et al. Prognostic implications of Tc-99m sestamibi viability imaging and subsequent therapeutic strategy in patients with chronic coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol. 2000;36:739–745