Questions and Answers


1.     What is myocardial viability and how do we identify it?


When we question the viability of a dysfunctional myocardial region, we are generally referring to the potential for this region of living myocytes to gain improved contractile function with revascularization. We must realize, however, that contractility of a myocyte is not the sole determinant of viability. Other aspects of viability include membrane transport function integrity and metabolic function. So when we consider revascularization of a myocardium with reduced systolic function we should be aiming not exclusively for improved LVEF but also for other benefits such as improved effort capacity that can be accrued from improved diastolic function, recurrent CHF admissions, recurrent myocardial infarction, further re-modelling  and prevention of sudden death.



2.     Describe 4 types of abnormal but viable myocardium


There is myocardium (usually subepicardial) that has survived a non STEMI  but is subtended by a stenosis which can make it reversibly ischemic and a source for angina or

angina equivalent. The subendocardial scar teathers the viable component and limits its motion. Revascularizatioin might not improve the function of the segment but provide other benefits such as preventing functional decline, recurrent MI and sudden death. There is stunned viable myocardium which has temporarily lost its contractile function due to an ischemic insult without infarction. Given hours to weeks of restored perfusion, this myocardium will normalize its contractile function completely. There is hibernating viable myocardium which is chronically hypoperfused due to a subtotal or total coronary occlusion. Its metabolism changes in response to hypoperfusion to primarily glucose production and utilization at the expense of fatty acid utilization. Ultrastructural damage contributes to an irreversible component of lost contractile function. Revascularization may improve contracitile function over many months but rarely restores contractile function to normal. Then there is myocardium which is normally perfused but which has suffered an irreversible loss of contractile function due to chamber dilatation or remodelling and chronic stretching of the contractile elements

3.     Contrast the physiology of normal, stunned, hibernating and infarcted myocardium


 The continuum from normally perfused myocardium to scar we also have the concept of repetitively stunned myocardium. Thus normal myocardium subtended by a normal or non-obstructed coronary has normal coronary blood flow which augments 3-4 fold with maximal vasodilatation. Repetitively stunned hypo-contractile myocardium is subtended by a coronary vessel with a stenotic lesion giving normal resting coronary blood flow but reduced augmentation in flow with maximal vasodilatation. Hibernating  hypo-contractile myocardium receives a tenuous coronary blood supply from a suboccluded vessel .It has reduced resting  coronary blood flow and no significant augmentation in flow with maximal vasodilation  Finally scarred myocardium  has virtually no coronary perfusion and no contractile function

Description: Description: schematic


4.     Name the most important reason why dysfunctional viable myocardium predicted to improve with revascularization fails to do so


This study from the surgical literature showed that a major reason why dysfunctional myocardial segments expected to improve with revascularization fail to do so was ventricular remodelling. The larger the left ventricular cavity the more stretched the myofibers, the less likely that function is regained as evidenced by an improved LVEF. Notice the inverse relationship between cavity end-systolic volume and the propensity for LVEF to change positively


Description: Description: remodelling


5.     What other reasons are there for failure of dysfunctional viable myocardium to improve post revacularization


There are additional reasons why the identification of dysfunctional viable myocardium preop might not translate into improved regional or global LV function postop. Perioperative untoward events including operative ischemic necrosis or graft thrombosis might trump the expected improvement. Inability to completely revascularize the dysfunctional viable areas could also interfere. Finally not waiting long enough to reassess cardiac function postoperatively could prevent the recognition of improved LV function. It might take up to a year for hibernating myocardium to show improvement after revascularization


6.     How can myocardial viability be assessed noninvasively


Viability of dysfunctional myocardium can be assessed in a number of ways. The first is by measuring myocardial perfusion. This can be accomplished by single photon emission computed tomography using Thallium-201 or Tc99m Sestamibi. Thallium requires intact cellular membrane function and Tc99m Sestamibi requires intact mitochondrial function for retention. This can also be accomplished by positron emission tomography using perfusion tracers Rubidium or N13 ammonia.The second is by evaluating contractile reserve. The myocardial function is assessed examining how it responds to an intravenous agent that augments myocardial contractility such as dobutamine. Typically, this  is accomplished with echocardiography but can also be done with MRI. The third method evaluates the metabolic function of the myocytes. All living myocytes utilize glucose but ischemic cells preferentially use it because fatty acid oxidation is suppressed. The fourth method tries to identify scarred myocardium. This requires MRI with injection of gadolinium to see delayed contrast enhancement of scarred myocardium


7.     Describe a practical approach to the radio-isotopic detection of viable myocardium


Begin with myocardial perfusion analysis, iI is important to emphasize that resting preserved perfusion does imply myocardial viability. However, only by stress perfusion can one be more sure that the segment is being perfused by an artery with a hemodynamically signifcant stenosis. If one can prove Metabolic imaging with PET to detect dysfunctional viable imaging is based on the suppression of fatty acid oxidation in the chronically ischemic myocyte and the parallel augmentation in glucose uptake and glycolysis. As a result the uptake of fluorine 18 deoxyglucose is disproportionately high in the chronically ischemic tissue. FDG imaging is always performed in series with resting perfusion imaging with rubidium or N13 ammonia in viability assessment. Four patterns can be observed. Reduced perfusion associated with preserved or enhanced FDG uptake ( so-called perfusion –metabolism mismatch) ,reflects myocardial viability with reduced function due to hibernation or repetitive stunning. The pattern of normal perfusion and metabolism also identifies viable myocardium but is not as predictive for functional recovery after revascuarizaion. Proportional reduction in perfusion and FDG uptake, the perfusion-metabolism match reflects nonviable myocardium that predicts no recovery of function post revascularization. The pattern of normal or near normal perfusion with reduced FDG uptake , the reversed perfusion-FDG mismatch has been described in the context of LBBB ,right ventricular pacing, Takatsubo cardiomyopathy.



8.     What randomized data supports the clinical utility of PET FDG/ Rb or NH3 ammonia imaging in viability detection?


In a study of 450 patients with severe LV dysfunction due to coronary artery disease, Beanlands randomized patients to either a PET guided therapy or no PET. That is, patient therapy (medical therapy alone versus revascularization ) was based on PET results in half the patients. What they found was that when physicians adhered to recommendations regarding revascularization based on the PET /rubidium results, there was a clinical benefit for their patients over the patients who did not get PET studies. Beanlands also found that there was a clear quantitative relationship between the amount of hibernating myocardium  ( PET metabolism/perfusion mismatch) and the hazard ratio for revascularization. When the PET mismatch size exceeded 7% of the myocardium, the hazard ratio in favour of revascularization became statistically significant.




9.     What was the STICH trial ?


The STICH trial was the first to assess the value of CABG in patients with severe resting left ventricular function with an LVEF of under 35%. 1212 patients  were randomized. Patients with disabling angina were excluded .While the primary endpoint of total mortality did not reach statistical significance in the NEJM report, it has on further follow-up and will undoubtedly show it when 10 year follow-up results are presented. The secondary endpoints of cardiovascular death and cardiovascular death or hospitalization for heart failure did reach statistical significance



10.                        What were the results of the STICH myocardial viability substudy?


About half of the patients in the study underwent myocardial viability testing with either SPECT (480 patients) or dobutamine echocardiography (170 patients) or both (150 patients). Over 80 percent of the patients were deemed to be viable. While on univariate analysis the presence of viability predicted better patient outcome there was no interaction with the mode of therapy. The presence of viability did not predict better outcome with revascularization and the absence of viability did not predict worse outcome with revascularization. These counter-intuitive results has led to a reassessment of the need for viability testing in patients with severe LV dysfunction who are being considered for revascularization. For SPECT, patients with viability were defined as those with 11 or more viable segments on the basis of relative tracer activity. For dobutamine echocardiography, patients with viability were defined as those with 5 or more segments with abnormal resting systolic function but manifesting contractile reserve during dobutamine administration.


11.                        Why might the STICH trial not showed the utility of myocardial viability testing?


There are a number of reasons why the results of the viability sub-study came out as they did. Firstly, this was a nonrandomized trial. Investigators were asked to do viability studies in all recruited patients and ones were done in roughly half. Most of the patients were deemed viable. The lack of patients who had non-viability ( roughly 100 patients) might have obscured the interaction between viability and mode of therapy. The imaging techniques used can be criticized based on lack of ischemia testing in the SPECT nuclear patients ( a proportion just had rest-rest Thallium) and the absence of the more precise techniques , namely PET and MRI. It is these techniques that are particularly needed in patients with the most severe left ventricluar dysfunction. Limited resolution techniques like SPECT perform less well when LV dysfunction is most severe. The use of a binary definition of viability can be criticized as well. The SPECT definition of viability encompassed both normal and dysfunctional but viable segments without making a distinction between the 2 conditions. Intuitively, the most clinical benefit should come from revascularizing dysfunctional segments. By including normal segments in the definition, the benefit of revascularization could have been watered down. Finally, the likelihood of improved outcome depends on the spatial coherence between the site of dysfunction but viable myocardium and coronary anatomy. CABG will do little good if the location of the obstruction in the target vessel and the site of graft insertion does not provide an adequate augmentation of perfusion to the viable but dysfunctional segment. For example, if a patient has a proximal and mid obstruction in the LAD and all the dyfunctional but viable myocardium in the LAD territory is proximal, it will do little good to place a LIMA distal to the mid LAD obstruction. If many of the conduits did not accomplish improved perfusion to the very myocardium requiring it, the benefits of identifying  these myocardial segments a priori is moot.

Despite all these criticisms, the consensus is that after STICH, myocardial viability testing should not be the sole determinant for whether or not to proceed with revascularization. Thus a patient with 3 vessel disease, severe LV dysfunction, good targets and low comorbidities might merit revascularization even without viability testing especially if angina is present. On the other hand, a patient with very poor LV function, without angina or demonstrable ischemia on stress perfusion, and with comorbidities and less than ideal conduits would be a good candidate for sophisticated viability testing.  The ACC/AHA might have been a little hasty in downgrading the use of viability testing to a class 2b indication, presumably based on STICH results.

In most cases, the patient should have coronary anatomy and presence or absence of reversible ischemia defined before deciding to add viability testing. This algorithm is in keeping with a post STICH approach.