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(Circulation. 1995;91:1894-1895.)
© 1995 American Heart Association, Inc.

Articles

Different Roads to the Assessment of Myocardial Viability

Lessons From PET for SPECT

Heinrich R. Schelbert, MD

From the Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Heinrich R. Schelbert, MD, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-1735.

	Introduction

Top Introduction References

 
The assessment of myocardial viability remains clinically important, yet diagnostically challenging. Tamaki et al¹ probe various approaches with positron emission tomography (PET). Since myocardial viability refers to a state of reversible impairment of contractile function, the authors correctly measure the accuracy of each approach against the postrevascularization outcome in systolic segmental wall motion as a yardstick of myocardial viability. The investigators conclude that (1) severe flow reductions accurately define myocardium as nonviable. In contrast, mild to modest reductions discriminate only poorly between viable and nonviable tissue. (2) The addition of stress-induced defects incrementally improves the identification of viable myocardium, even though the reasons for such improvement remain uncertain. (3) The combined evaluation of rest blood flow and ¹⁸F-deoxyglucose uptake as a tracer of exogenous glucose utilization distinguishes most reliably between viable and nonviable myocardium. As the authors acknowledge, the latter observation on the high predictive accuracy of blood flow metabolism patterns represents an extension of their earlier work.^{2 3} Together with other previous investigations,^{4 5 6 7} the present data further strengthen the case of flow metabolism patterns as accurate indexes of the myocardial state. Yet, the study does not answer clinically or therapeutically critical questions. It would have been important to know the effects of revascularization on global left ventricular function, clinical symptoms, or both and how such changes might relate to mismatches and their extent.^{4 8} Thus, we must rely on changes in segmental function as surrogates of changes in global function.

Although the negative predictive accuracy of the flow metabolism matches, 92%, resides at the upper end of the reported spectrum (ranging from 74% to 100%), the positive predictive accuracy, 76%, resides at the lower end of the spectrum, ranging from 73% to 95%.^{4 5 6 7 9} Several reasons might account for this. First, although the adequacy of the revascularization was evaluated anatomically on repeat angiography, it does not necessarily prove that nutrient blood flow had indeed been restored sufficiently. Second, myocardial ¹⁸F-deoxyglucose uptake was evaluated in the fasted state, whereas most laboratories rely on the post–glucose loading state.^{4 5 6 7} When the same patients are evaluated in both the glucose-loaded and the fasted state, as recently reported from our laboratory, the latter condition increases the prevalence of flow metabolism mismatches.¹⁰ Regionally increased ¹⁸F-deoxyglucose uptake, seen only in the fasted state, may represent small islands of viability without functional consequences in response to revascularization. Thus, the fasted approach may be overly sensitive yet highly specific. A third possibility exists. A direct correlation between the postrevascularization gain in segmental systolic wall motion and the prerevascularization severity of the wall motion impairment has been described.¹¹ The present study provides little if any information on wall motion severity. If the wall motion impairment was relatively mild, as the only modest reduction in left ventricular ejection fraction might imply, it could account for the lower incidence in postrevascularization improvements in wall motion.

A second interesting aspect of this study is the comparison of the resting flow defects with the postrevascularization changes in segmental systolic wall motion. It is not surprising that severe (>50%) flow reductions reflected mostly nonviable myocardium. Cell survival and, thus, viability depend on delivery of substrates as well as on removal of inhibitory metabolites. Thus, some degree of residual tissue blood flow becomes critical. The threshold level of 50% appears high, yet it is similar to that noted on single photon emission computed tomography (SPECT)¹² and, as postulated by the authors, may be artifactual because of high background activity. Conversely, the poor positive predictive value for only mild to modest flow reductions (<50% below control) similarly is not surprising, even if it is at odds with recent findings on SPECT ²⁰¹Tl or ^99mTc-sestamibi imaging.¹² On the one hand, flow reduction involving the entire myocardial wall, although with transmural differences, might account for a modest overall flow reduction. On the other hand, it may also result from the coexistence of scar tissue in the endocardial and of normal myocardium in the epicardial half of the myocardial wall. Restoration of blood flow would be anticipated to improve wall motion only in the first scenario but not in the second one. Therefore, the variable functional outcome after revascularization is expected.

The discrepancy of the PET findings with those on SPECT imaging with ²⁰¹Tl or ^99mTc-sestamibi remains unexplained.¹² This discrepancy leads to the third major point of the Tamaki report,¹ the incremental effect of stress-induced flow defects on the positive predictive accuracy. The present study does not offer information on whether exercise stress produced new flow defects, worsened already existing defects, or both. If such stress-induced defects occurred in segments with already modestly severe flow defects at rest, the mechanisms accounting for the added positive predictive accuracy would seem rather complex. If, as is more likely, a segmental wall motion abnormality was present together with only a mild flow defect or no defect at all, the exercise-induced flow deficit might have been an integral part of "repetitive stunning." Blood flow at rest may be well preserved or even normal in "repetitively stunned myocardium," yet wall motion is reduced and, importantly, flow reserve is markedly attenuated or even absent.¹³ An increase in demand thus produces ischemia followed by stunning. Revascularization eliminates the culprit. Thus, wall motion would improve. The situation may be similar for "viable myocardium" as identified by only mild to modest reductions in ^99mTc-sestamibi uptake¹² or with ²⁰¹Tl reinjection.¹⁴ In both situations, the tracer uptake appears to reflect mostly blood flow, unlike the ²⁰¹Tl uptake on late imaging, which more strongly reflects the potassium pool. Even though rest blood flow and thus flow tracer uptake may be relatively normal if dysfunctional myocardium results from "repetitive stunning," it is likely to exhibit an artifactual flow defect due to a partial volume–related underestimation of the true tracer tissue concentrations. This is because of a decline in the average wall thickness due to a loss of systolic thickening together with the poorer spatial resolution of SPECT. Induction of wall motion abnormalities alone resulted in a 37±9% artifactual "flow defect."¹⁵ If, in the case of SPECT studies of viability, flow defects of <50% severity are indeed frequently artifactual and partial volume–related and true blood flow is normal or minimally reduced, it might explain the high predictive accuracy of SPECT for viability assessment.

While the present study leaves a number of questions on myocardial viability assessment unanswered, it nevertheless is an important contribution to the PET approach for identifying reversible dysfunction, for offering some potential insights into underlying mechanisms, and especially for its relevance for viability assessments versus SPECT imaging.

	Footnotes

 
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.

Received January 26, 1995; accepted January 26, 1995.

	References

Top Introduction References

 

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3. Tamaki N, Ohtani H, Yamashita K, Magata Y, Yonekura Y, Nohara R, Kambara II, Kawai C, Hirata K, Ban T, Kinishi J. Metabolic activity in the areas of new fill-in after thallium-201 reinjection: comparison with positron emission tomography using fluorine-18-deoxyglucose. J Nucl Med. 1991;32:673-678. [Abstract/Free Full Text]
   
4. Tillisch J, Brunken R, Marshall R, Schwaiger M, Mandelkern M, Phelps M, Schelbert HR. Reversibility of cardiac wall motion abnormalities predicted by positron tomography. N Engl J Med. 1986;314:884-888. [Abstract]
   
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