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(Circulation. 1996;94:2681-2684.)
© 1996 American Heart Association, Inc.

Articles

Comparison of ²⁰¹Tl Scintigraphy and Low-Dose Dobutamine Echocardiography for the Noninvasive Assessment of Myocardial Viability

George A. Beller, MD

the Cardiovascular Division, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville.

Correspondence to George A. Beller, MD, Chief, Cardiovascular Division, Box 158, University of Virginia Health Sciences Center, Charlottesville, VA 22908.

Key Words: Editorials • echocardiography • stunning, myocardial • imaging • isotopes

	Introduction

Top Introduction References

 
Noninvasive assessment of myocardial viability has proved clinically useful to distinguish hibernating or stunned myocardium from irreversibly injured myocardium in patients with chronic CAD or recent myocardial infarction who exhibit severe regional and global LV dysfunction. A variety of noninvasive methodologies are undergoing investigation and validation for determination of accuracy in the detection of preserved viability in akinetic and severely hypokinetic myocardium. These techniques include SPECT perfusion imaging with ²⁰¹Tl or one of the new ^99mTc-labeled agents, such as ^99mTc sestamibi; SPECT imaging of ¹²³I-labeled fatty acid analogs; PET imaging of regional flow and ¹⁸F-labeled FDG uptake; and assessment of inotropic reserve by use of dobutamine echocardiography. A major clinical objective when one of these techniques is used in CAD patients with ischemic cardiomyopathy is to identify those who will benefit most from coronary revascularization with respect to postoperative improvement in regional and global LV function, heart failure symptoms, functional capacity, and enhanced long-term survival.

Several observational studies^{1 2 3 4} showed substantial survival benefit with revascularization compared with medical therapy in patients whose low ejection fraction was primarily due to viable but hibernating myocardium. Similarly, preliminary data⁵ suggest that patients with low ejection fractions, multivessel CAD, and preserved viability who undergo CABG have a lower perioperative mortality and morbidity and a greater long-term survival rate than patients with a comparable degree of LV dysfunction and angiographic extent of CAD who undergo surgery but who manifest poor myocardial viability preoperatively. Gioia et al¹ reported a 13% annual mortality rate in CAD patients with LV dysfunction and presence of viability by ²⁰¹Tl criteria who were treated medically compared with 6% for those with comparable viability who underwent revascularization. DiCarli et al² reporteda 50% mortality rate at 1 year in patients with CAD, LV dysfunction, and evidence of viability by PET imaging who were treated medically compared with an 88% 1-year survival for those with viability who underwent CABG. This same group recently found that in patients with ischemic cardiomyopathy, the magnitude of improvement in heart failure symptoms after CABG was related to the preoperative extent and magnitude of myocardial viability.³ Among patients with evidence of viability by PET-FDG imaging, Lee et al⁴ found a 48% ischemic-event rate for medically treated patients and an 8% event rate for patients who underwent revascularization at 17±9 months. Similar poor outcomes for patients with preserved viability by PET imaging who were treated medically were reported by Eitzman et al⁶ and Yoshida and Gould.⁷ More recently, Williams et al,⁸ using dobutamine echocardiography for viability assessment, reported a higher cardiac event rate at 16±8 months after study in patients with viable or ischemic myocardium than in those with scar (43% versus 8%, respectively).

When patients with ischemic cardiomyopathy who are referred for cardiac transplantation undergo viability assessment, those who demonstrate myocardial viability have an excellent outcome when they undergo CABG instead of transplantation. In one study,⁹ 46 patients with a mean LV ejection fraction of 0.23±0.06 who underwent CABG instead of transplantation because of presence of viability had an 87% survival rate at 2 years. Thus, these studies indicate that the noninvasive assessment of viability provides useful prognostic information that may assist in better selection of patients with ischemic cardiomyopathy who will benefit from revascularization rather than medical therapy or cardiac transplantation. Those with the greatest extent of viability in regions of severe myocardial asynergy experience the greatest improvement in LV function and heart failure symptoms postoperatively and seem to have an excellent short-term survival rate.

Although all the noninvasive techniques for detection of viability cited above have yielded good positive and negative predictive values for predicting functional recovery or lack of functional recovery, respectively, after revascularization, considerable discordant findings have been reported in some studies that compared ²⁰¹Tl scintigraphy with dobutamine echocardiography for viability assessment.^{10 11 12 13 14} The major discordant observation is that more asynergic segments, particularly those that are akinetic, are viable by ²⁰¹Tl criteria (eg, >50% uptake on delayed images) than exhibit contractile reserve by dobutamine echocardiography, which yields a higher "sensitivity" for viability detection for the radionuclide approach. However, some of these studies, including the one published by Perrone-Filardi et al in this issue of Circulation,¹⁴ found that dobutamine echocardiography had a better positive predictive value for LV functional recovery after revascularization than ²⁰¹Tl scintigraphy^{12 13 14} or myocardial contrast echocardiography.¹⁵ The latter technique solely provides information relative to microcirculatory perfusion. This observation has led to the conclusion that perfusion imaging is "too sensitive" in detecting viability in myocardial segments that fail to show improved systolic function after revascularization.¹⁶ In contrast, the negative predictive value for predicting lack of functional improvement after revascularization is either comparable or higher with ²⁰¹Tl imaging compared with dobutamine echocardiography.

Perrone-Filardi et al¹⁴ studied 40 patients with CAD who had a mean LV ejection fraction of 0.45±0.10. Only 10 had three-vessel disease, and 18 underwent revascularization. Doses of 5 and 10 µg·kg^-1·min^-1 of dobutamine were infused, and the criterion for viability was an improvement in contractile function by one grade or more (eg, systolic thickening observed in an akinetic segment or reversion to normal thickening in a previously hypokinetic segment). Myocardial scan segments on SPECT images with ²⁰¹Tl activity of 50% of maximal activity were considered to be viable. Ninety-four percent of the 105 hypokinetic segments were viable by ²⁰¹Tl criteria, and 84% exhibited contractile reserve with dobutamine. The concordance rate was 82% between ²⁰¹Tl and dobutamine results in hypokinetic segments. In contrast, 77% of 155 akinetic segments were deemed viable by ²⁰¹Tl criteria but only 22% showed contractile improvement with dobutamine. Concordance between ²⁰¹Tl and dobutamine results was 43% in akinetic segments. When patients, rather than segments, were analyzed, 14 patients demonstrated viability in akinetic segments by ²⁰¹Tl criteria but not by dobutamine echocardiography. SPECT ²⁰¹Tl imaging had positive and negative predictive values for improvement in function in hypokinetic and akinetic segments after revascularization of 72% and 100%, respectively. This compared with 92% and 65% positive and negative predictive values, respectively, for dobutamine echocardiography. ²⁰¹Tl imaging had only a 51% positive predictive value for functional improvement after revascularization compared with 88% for dobutamine echocardiography when akinetic segments were analyzed separately. However, the negative predictive value for predicting a lack of functional improvement in akinetic segments after revascularization was lower for dobutamine echocardiography than ²⁰¹Tl imaging (76% versus 100%). These differences in predictive values are explained by a higher sensitivity but a lower specificity by ²⁰¹Tl viability criteria compared with dobutamine echocardiography viability criteria.

Similar observations were reported by Arnese et al¹² in 38 patients with an LV ejection fraction of 40%. SPECT ²⁰¹Tl imaging detected the presence of viable myocardium in 49 of 112 akinetic regions that did not respond to dobutamine. However, only 9 of these 49 segments that were judged viable by ²⁰¹Tl criteria but unresponsive to dobutamine showed postoperative improvement in wall motion. The overall positive predictive value of ²⁰¹Tl viability imaging for prediction of postoperative improvement in regional function was 33% compared with 85% for dobutamine echocardiography, despite a higher sensitivity of ²⁰¹Tl imaging for detection of viability (89% versus 74%). These authors concluded that "because ²⁰¹Tl SPECT overestimates the probability of postoperative improvement of dyssynergic segments, low-dose dobutamine echocardiography should be the preferred imaging technique for preoperative assessment of these patients." DeFilippi et al¹⁵ found a higher positive predictive value for prediction of improvement in systolic function in zones of asynergy after revascularization for dobutamine echocardiography than myocardial contrast echocardiography (85% versus 55%) and concluded that "contractile reserve during low-dose dobutamine infusion is a better predictor of functional recovery after revascularization in akinetic segments than perfusion."

It would be erroneous to conclude from the studies of Perrone-Filardi et al,¹⁴ Arnese et al,¹² and deFilippi et al¹⁵ that dobutamine echocardiography is a superior technique for assessment of myocardial viability compared with ²⁰¹Tl scintigraphy simply because a smaller percentage of myocardial segments that were judged viable by ²⁰¹Tl criteria demonstrated improved systolic thickening or wall motion after revascularization. Unfortunately, improvement in regional function within a few months after revascularization has emerged as the gold standard for evaluation of noninvasive techniques in regard to their accuracy in distinguishing viable from predominantly necrotic or scarred myocardium. For lack of a better gold standard, improvement in regional function after CABG or angioplasty is the standard most commonly adopted in clinical research studies. Experimental studies, however, that used a model of chronic low-flow ischemia in dogs to simulate short-term hibernation demonstrated ²⁰¹Tl uptake only in zones of viability as determined histologically.¹⁷ In fact, when coronary flow was reduced by 50% in these dogs, resulting in reversible akinesia, substantial ²⁰¹Tl uptake (>50%) was evident in akinetic zones. Interestingly, systolic thickening in these dogs negligibly increased in response to low-dose dobutamine. This is because even with an inotropic stress of only 5 µg·kg^-1·min^-1 of dobutamine, additional ischemia probably developed, which precluded the ability for enhanced function. Regional flow did not increase in response to dobutamine, which is required for stimulation of contractile reserve.

Several explanations have been proposed for why some akinetic segments in patients with chronic CAD demonstrate >50% uptake of ²⁰¹Tl compared with maximal uptake on resting images but do not improve function after revascularization.^{12 13 14 15 16 18} Perhaps the most plausible is that many of these akinetic segments comprise a mixture of scar (often confined to the endocardial layers) and normal myocardium, with adequate perfusion at rest to sustain cellular viability. Severe hypoperfusion confined to the endocardial layers of the myocardium can result in transmural akinesia despite normal midwall and epicardial blood flow.^{19 201}Tl uptake in this situation may exceed 50% of maximal uptake, since fibrosis may extend only from 25% to 35% of the transmural thickness of the asynergic myocardial region. Although revascularization may not improve resting function in this situation compared with the situation of severe resting regional asynergy without extensive scar (hibernation), improved long-term prognosis, attenuation of LV remodeling, and reduction in subsequent ischemic events with revascularization may be more prevalent than when no viability is detected by ²⁰¹Tl imaging. Thus, such patients may benefit from the preoperative identification of all viable segments, even if some will not show functional improvement after revascularization.

Another potential mechanism that would explain why segments that are viable by ²⁰¹Tl criteria do not respond to dobutamine relates to tethering of these segments to regions of extensive scar, which would inhibit recovery of systolic function after successful revascularization. Again, viability is not "overestimated" by ²⁰¹Tl scintigraphy. These tethered segments are indeed viable but cannot respond to an inotropic stimulus with enhanced regional thickening or wall motion. Finally, either some stenotic vessels that perfuse viable akinetic regions may not be bypassed at the time of surgery, or revascularization does not result in a significant increase in flow, so that resting wall motion remains depressed.

What is perhaps more clinically important than too great a sensitivity for ²⁰¹Tl imaging for viability detection is that quantitative ²⁰¹Tl scintigraphy has excellent negative predictive value to predict lack of improvement in regional and global LV function after revascularization. That is, most myocardial segments with <50% uptake of ²⁰¹Tl do not show enhanced function after revascularization. The accurate identification of nonviability is critical for decision making with respect to better selection of patients with ischemic cardiomyopathy who will benefit most from CABG. The greater the number of nonviable myocardial regions present, the lower is the probability of survival or enhanced global function and exercise capacity after revascularization. The lower negative predictive value for dobutamine echocardiography than ²⁰¹Tl imaging for prediction of lack of improvement after revascularization, as seen in the study by Perrone-Filardi et al,¹⁴ could potentially lead to rejection of some patients for revascularization who indeed have more viability than can be discerned by assessment of contractile reserve by dobutamine infusion. Hence, for clinical decision making in an individual patient with multivessel CAD and a profound reduction in LV function, overestimation is preferable to underestimation of viability. Data reported to date show that patients with extensive areas of viability by ²⁰¹Tl criteria (even if detection was overestimated) do very well after CABG. In such patients, the greater the number of viable akinetic or severely hypokinetic segments identified preoperatively, the greater is the resting LV ejection fraction 6 weeks after CABG.²⁰

Nevertheless, despite this discussion of the similarities and differences between ²⁰¹Tl scintigraphy and dobutamine echocardiography for viability assessment, both techniques, when performed by well-trained and experienced individuals, provide an enormous amount of useful physiological information that translates to improved care of patients with severe CAD and LV dysfunction. Additional technical refinements of these noninvasive methodologies and additional prospective clinical research studies that compare the two techniques, when both tests are performed with comparable expertise, will surely be forthcoming. For example, the study by Perrone-Filardi et al¹⁴ published in this issue of Circulation showed that acquiring 24-hour ²⁰¹Tl redistribution images changed the interpretation with regard to the viability provided by quantitative rest–4-hour ²⁰¹Tl image analysis in only 2% of 219 persistent defects at 4 hours. This confirms the data of Dilsizian et al,²¹ who reported that 24-hour imaging after a resting injection of ²⁰¹Tl changed the interpretation of viability in only 4 of 127 myocardial segments that corresponded to irreversible defects at 4 hours.

Other advances in SPECT imaging that may prove advantageous for improved detection of viability are the examination of fatty acid metabolism with radioiodinated fatty acid analogs, performance of FDG imaging with conventional three-headed SPECT cameras and a special collimator, use of ^99mTc-labeled perfusion agents such as sestamibi and tetrofosmin (after validation for use as viability agents), and correction of ²⁰¹Tl SPECT images for attenuation to yield more accurate information relevant to physiological tracer uptake. With respect to stress echocardiography, more objective measurement of changes in regional systolic function is needed to reduce subjectivity of the technique. Also, evaluation of microvascular integrity with myocardial contrast echocardiography may provide additional useful information to the determination of inotropic reserve with dobutamine for optimal assessment of myocardial viability by use of the echocardiographic technique.^{15 18}

In conclusion, the field of noninvasive imaging of myocardial viability remains active and exciting, as old techniques are refined and applied to the improvement of patient care and new techniques emerge that present clinician-investigators with new challenges to evaluate their worth and cost-effectiveness in this era of managed care and cost reductions.

	Selected Abbreviations and Acronyms

 

CABG = coronary artery bypass graft surgery CAD = coronary artery disease FDG = fluorodeoxyglucose LV = left ventricular PET = positron emission tomography SPECT = single-photon emission computed tomography

	Footnotes

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

	References

Top Introduction References

 

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This Article Extract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beller, G. A. Search for Related Content PubMed PubMed Citation Articles by Beller, G. A.