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
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
5. What other reasons are there for failure of dysfunctional viable myocardium to improve post revacularization
are additional reasons why the identification of dysfunctional viable
myocardium preop might not translate into improved
regional or global
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?
study of 450 patients with severe
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
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
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
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.