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(Circulation. 1996;94:2712-2719.)
© 1996 American Heart Association, Inc.

Articles

Assessment of Myocardial Viability in Patients With Chronic Coronary Artery Disease

Rest–4-Hour–24-Hour ²⁰¹Tl Tomography Versus Dobutamine Echocardiography

Pasquale Perrone-Filardi, MD, PhD; Leonardo Pace, MD; Mariella Prastaro, MD; Fiorenzo Squame, MD; Sandro Betocchi, MD; Andrea Soricelli, MD; Federico Piscione, MD; Ciro Indolfi, MD; Teresa Crisci, MD; Marco Salvatore, MD; Massimo Chiariello, MD

the Divisions of Cardiology (P.P.-F., M.P., S.B., F.P., C.I., T.C., M.C.) and Nuclear Medicine (L.P., F.S., A.S., M.S.), "Federico II" University Medical School, Naples, Italy.

Correspondence to Pasquale Perrone-Filardi, MD, PhD, Cattedra di Cardiologia, Universita degli Studi "Federico II," Via S Pansini 5, I-80131 Napoli, Italy.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background To date, late redistribution after resting ²⁰¹Tl injection has not been evaluated. In addition, the concordance between resting ²⁰¹Tl imaging and dobutamine echocardiography in identifying viable myocardium has not been assessed.

Methods and Results Forty patients with coronary artery disease underwent rest–4-hour–24-hour ²⁰¹Tl tomography and dobutamine echocardiography (5 to 10 µg·kg^-1·min^-1). Late redistribution occurred in 46 (21%) of 219 persistent defects at 4 hours. Systolic function and contractile reserve were similar among persistent defects at 4 hours with and without late redistribution. Contractile reserve was more frequent in segments with normal ²⁰¹Tl uptake (59%), completely reversible defects (53%), or mild to moderate defects at 4 hours (56%) compared with severe defects (14%; P<.02 versus all). Of 105 hypokinetic segments, 99 (94%) were viable by ²⁰¹Tl, and 88 (84%) showed contractile reserve. In contrast, of 155 akinetic segments, 119 (77%) were viable by ²⁰¹Tl, but only 34 (22%) had contractile reserve. Concordance between ²⁰¹Tl and dobutamine was 82% in hypokinetic segments but 43% in akinetic segments. In 109 revascularized segments, positive accuracy for functional recovery was 72% for ²⁰¹Tl and 92% for dobutamine, whereas negative accuracy was 100% and 65%, respectively. Sensitivity was 100% for ²⁰¹Tl and 79% for dobutamine.

Conclusions Late redistribution occurs in one fifth of persistent defects at 4 hours, and it does not correlate to systolic function or contractile reserve. Dobutamine and ²⁰¹Tl yield concordant information in the majority of hypokinetic segments, whereas concordance is low in akinetic segments. Dobutamine demonstrates higher positive accuracy and sensitivity in predicting recovery of dysfunctional myocardium, whereas ²⁰¹Tl shows higher negative predictive accuracy but reduced positive accuracy.

Key Words: scintigraphy • echocardiography • myocardium • coronary disease

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Rest–4-hour redistribution ²⁰¹Tl scintigraphy^{1 2 3 4 5 6 7} and low-dose dobutamine echocardiography^{8 9 10 11} have been proposed for use in identifying viable dysfunctional myocardium in patients with coronary artery disease. In previous studies that used stress or rest-redistribution ²⁰¹Tl scintigraphy,^{3 5 7 12 13 14} segments with normal uptake, ²⁰¹Tl redistribution, or mild to moderate persistent defects have been shown to represent viable myocardium. However, up to 23% of dysfunctional segments showing severely reduced ²⁰¹Tl uptake at 4-hour redistribution improve after revascularization, whereas 46% of segments with a mild or moderate persistent ²⁰¹Tl defect do not.⁵ Therefore, it could be hypothesized that in some hypoperfused yet viable segments, imaging at 4 hours after rest injection may be too early to detect redistribution, and prolonged imaging time would be required to allow reversibility of a defect to be visualized, as previously reported for exercise imaging.^{15 16} In resting ²⁰¹Tl studies, however, the occurrence of late redistribution and its impact on the evaluation of myocardial viability have not been investigated.

Recently, dobutamine echocardiography has also been reported to be accurate in identifying viable dysfunctional myocardium.^{8 9 10 11} As yet, however, no studies have compared the information on myocardial viability provided by rest-redistribution ²⁰¹Tl scintigraphy and by dobutamine echocardiography in the same patients.

Therefore, the aims of the present study were to evaluate the incidence of late redistribution after resting ²⁰¹Tl injection and its impact on viability assessment and whether rest-redistribution ²⁰¹Tl tomography and dobutamine echocardiography yield comparable viability information.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patient Population
Forty consecutive patients (35 men; age, 57±9 years) with chronic coronary artery disease who showed regional myocardial dysfunction at rest by echocardiography and by contrast ventriculography were studied. No patient had had heart failure or unstable angina for at least 1 month before the study. Maximal body weight was 86 kg, and body mass index did not exceed 26 kg/m². Thirty (75%) of the patients suffered a previous myocardial infarction, which occurred at least 3 months before the protocol studies in 29 patients and 3 weeks before the studies in 1 patient. Coronary angiography documented three-vessel disease in 10 patients, two-vessel disease in 10, and single-vessel disease in 20. Subocclusive stenosis or occluded vessels were present in 19 patients. Left ventricular ejection fraction at rest, measured in 35 patients, averaged 45±10%. In 18 of these patients, ejection fraction was 45%.

Study Protocol
All patients underwent rest–4-hour–24-hour ²⁰¹Tl single photon emission computed tomography (SPECT) and two-dimensional echocardiography at rest and during dobutamine infusion. The two studies were performed in the same day in 38 patients, 1 day apart in 1 patient, and 1 week apart in 1 patient. In all but 1 patient, calcium-antagonists and oral nitrates had been withdrawn for at least 48 hours, ß-blockers for at least 72 hours, and transdermal nitrates for at least 12 hours before the protocol studies. One patient was taking oral nitrates at the time of the protocol studies. Resting echocardiography was repeated in 18 patients 43±39 days (range, 20 to 196 days; median, 32 days) after successful revascularization (coronary angioplasty in 11 patients and coronary artery bypass grafting in 7) while the patients were not taking drugs. No patients had clinical, ECG, or biochemical evidence of perioperative infarction, and all were asymptomatic at follow-up. Informed consent was obtained from each patient before the study protocol, which had been approved by the Institutional Ethical Committee.

²⁰¹Tl Imaging
After an overnight fast, patients underwent quantitative SPECT after the administration of 2 (first 16 patients) or 3 mCi of ²⁰¹Tl IV under resting conditions. SPECT images were acquired 15 to 20 minutes, 4 hours, and 24 hours after ²⁰¹Tl injection, as previously described.¹¹ Thirty-two images were acquired from a 30° right anterior oblique to a 60° left posterior oblique view in 6° increments. Acquisition of each image lasted 30 seconds for the initial and 4-hour images and 60 seconds for 24-hour images. For each set of images, slices that were three pixels thick were reconstructed along the short, horizontal, and vertical long axes of the heart.^{6 11 13 14} The thickness of the reconstructed slices was chosen to incorporate a substantial amount of myocardium in each myocardial segment and to minimize misalignment with echocardiographic myocardial segments.

In each patient, four consecutive slices from the short-axis series and two from the horizontal and vertical long-axis series were selected for each set of images after visual alignment for subsequent quantitative ²⁰¹Tl analysis.¹¹ Image analysis was performed by two operators unaware of the echocardiographic and clinical data.

Echocardiography
Two-dimensional echocardiography was performed with a 2.5-MHz transducer and commercially available scanner (Hewlett Packard, Sonos 1000) under resting conditions and during the last 3 minutes of each dobutamine infusion level. Echocardiographic standard-view images were acquired with the patient in the left lateral decubitus position and were recorded on a 12.5-mm VHS videotape. After baseline echocardiography, dobutamine infusion was started at the initial dose of 5 µg·kg^-1·min^-1 for 5 minutes; it was then increased to 10 µg·kg^-1·min^-1 for 5 additional minutes in all but two patients. Blood pressure and 12-lead ECG were monitored throughout the study. No patients reported major side effects. In two patients, dobutamine infusion had to be interrupted for ventricular bigeminy. Heart rate was 75±10 bpm at baseline and 88±14 bpm at the end of peak dose infusion (P<.01). Systolic blood pressure was 130±18 mm Hg at baseline and did not change at the end of the study (135±19 mm Hg; P=NS).

Data Analysis
Quantitative ²⁰¹Tl Analysis
For each patient, regional ²⁰¹Tl activity was measured on the short-axis tomograms by use of a semiautomatic analysis program.¹¹ Short-axis tomograms were divided into six sectors representing the posterolateral, inferior, posteroseptal, anteroseptal, anterior, and anterolateral myocardium. Apical ²⁰¹Tl activity was measured from vertical and horizontal long-axis tomograms.¹¹ Regional ²⁰¹Tl activity was expressed as percent of maximal ²⁰¹Tl activity. The sectors from two consecutive three-pixel-thick short-axis tomograms were then grouped and averaged. Thus, 13 myocardial regions were analyzed in each patient. A ²⁰¹Tl defect was defined when ²⁰¹Tl activity measured <80% of maximal activity.^{11 17} Redistribution was defined when relative ²⁰¹Tl activity at 4-hour or 24-hour imaging increased 12 percentage points above the initial value. This cutoff was chosen on the basis of reproducibility studies performed in 10 additional male patients (age, 56±7 years) with chronic coronary artery disease in whom a resting ²⁰¹Tl study (3-mCi injection) was repeated twice, 1 week apart. The two studies were blindly analyzed, and regional ²⁰¹Tl activity was measured in 240 corresponding myocardial regions. Mean difference in regional activity between the two studies was 6.6±5.3%. In addition, the reproducibility of ²⁰¹Tl analysis was assessed in 22 patients in whom quantitative analysis was repeated twice by different operators. The average difference between the two measurements was 0.5±8.2%. On the basis of the reproducibility data, the average difference plus one standard deviation between two different studies (ie, 12%) was chosen as the cutoff to define redistribution.^{18 19} Persistent defects at 4- and 24-hour imaging were classified as mild to moderate when ²⁰¹Tl activity was 50% of maximal activity and severe when ²⁰¹Tl activity was <50%. Segments with persistent and severe reduction of ²⁰¹Tl activity were considered nonviable, whereas all other segments were considered viable.^{5 6 11 12 13 14}

Echocardiographic Analysis
Echocardiographic undigitized images were analyzed off-line from the videotape playback by continuous display by two independent operators unaware of the scintigraphic and angiographic results. Regional wall motion was evaluated at the chordal, papillary muscle, and apical levels. To match ²⁰¹Tl data, short-axis echocardiographic images were divided into six myocardial segments corresponding to the scintigraphic segments. The apex was considered a single myocardial region in the echocardiographic analysis, as it was for ²⁰¹Tl analysis.¹¹ Wall motion and systolic thickening were graded semiquantitatively by use of a scoring system in which 1=normal, 2=hypokinesia, 3=akinesia, and 4=dyskinesia. Improvement of contractile function was defined when functional score improved 1 grade. Regional systolic dysfunction was defined when a score 2 was assigned to a myocardial segment in at least two different echocardiographic views.

Statistical Analysis
All data are expressed as mean±1SD. Multiple ² analysis was used to compare incidence of events among groups. Four-by-three ² analysis was applied to data in Table 1, and two-by-three ² analysis was applied to data in Table 3. Statistics were applied to evaluate concordance in dysfunctional segments.

View this table: [in this window] [in a new window]   Table 1. Regional Systolic Function at Rest and Contractile Reserve in Relation to Rest–4-Hour 201Tl Findings

View this table: [in this window] [in a new window]   Table 3. Regional Systolic Function at Rest and Contractile Reserve in Persistent 201Tl Defects at 4-Hour Redistribution With and Without Late Redistribution

	Results

Top Abstract Introduction Methods Results Discussion References

 
A total of 520 myocardial segments were analyzed in 40 patients. Of these, 171 (33%) had normal ²⁰¹Tl uptake, 86 (17%) showed a completely reversible ²⁰¹Tl defect, and 44 (8%) showed a partially reversible ²⁰¹Tl defect. The remaining 219 segments (42%) exhibited a persistent ²⁰¹Tl defect at 4-hour redistribution. Of these latter defects, 176 (34%) were mild to moderate and 43 (8%) were severe. Of 520 myocardial segments evaluated, 260 (50%) showed normal function at rest, 105 (20%) were hypokinetic, and the remaining 155 (30%, averaging 3.9 per patient) were akinetic (152 segments) or dyskinetic (3 segments). The three dyskinetic apical segments corresponded to persistent and severe ²⁰¹Tl defects, and they were categorized with the akinetic segments.

Regional Systolic Function at Rest and Contractile Reserve in Relation to Rest–4-Hour ²⁰¹Tl Uptake
Normal function was observed in 113 (66%) of 171 segments with normal ²⁰¹Tl uptake, in 46 (53%) of 86 segments with completely reversible defects, in 17 (39%) of 44 segments with partially reversible defects, and in 83 (47%) of 176 segments with persistent mild to moderate defects (Table 1). Among groups of ²⁰¹Tl viable regions, systolic function significantly differed in relation to ²⁰¹Tl uptake (P=.003). In contrast, only 1 (2%) of 43 segments with severely reduced uptake had normal function (P<.01 versus all; Fig 1). The percent of akinetic segments did not differ among segments with normal ²⁰¹Tl uptake (29 [17%] of 171 segments), completely (21 [24%] of 86) or partially reversible defects (18 [41%] of 44), and persistent mild to moderate defects (51 [29%] of 176). In contrast, the percent of akinetic segments was significantly higher among those with severely reduced uptake (36 [84%] of 43; P<.01 versus all).

View larger version (21K): [in this window] [in a new window]   Figure 1. Percent of myocardial regions showing normal systolic function at rest by echocardiography in relation to regional rest–4-hour redistribution 201Tl uptake. MM indicates mild to moderate persistent 201Tl defects at 4 hours; PR, partially reversible 201Tl defects; and TR, completely reversible 201Tl defects. *P<.01 compared with all other groups.

The percent of dysfunctional segments that improved during dobutamine was significantly higher in those with normal ²⁰¹Tl uptake (34 [59%] of 58 segments), complete redistribution (21 [53%] of 40), and mild to moderate persistent defects (52 [56%] of 93) compared with severe persistent defects (6 [14%] of 42; P<.02 versus all; Fig 2). A linear correlation was found between ²⁰¹Tl uptake at 4 hours and the percent of segments with contractile reserve (r=.94; P<.005; Table 2).

View larger version (21K): [in this window] [in a new window]   Figure 2. Percent of myocardial regions that showed abnormal systolic function at rest by echocardiography but evidence of contractile reserve during dobutamine infusion, in relation to rest–4-hour redistribution regional 201Tl uptake. *P<.02 compared with all other groups. Abbreviations as in Fig 1.

View this table: [in this window] [in a new window]   Table 2. 201Tl Uptake Intervals at 4-Hour Redistribution and Percent of Segments Showing Contractile Reserve and Functional Improvement After Revascularization

Late Redistribution in Relation to Initial ²⁰¹Tl Uptake
Redistribution at 24 hours occurred in 46 (21%) of 219 persistent ²⁰¹Tl defects at 4 hours, 42 (91%) of which were mild to moderate. In addition, complete reversibility at 24 hours was observed in 8 (18%) of 44 segments that showed only partial redistribution at 4 hours. The frequency of late redistribution was higher, although not significantly, in segments with mild to moderate persistent defects at 4 hours (42 [24%] of 176) compared with those with severe defects (4 [9%] of 43). These figures indicate that late redistribution changed the interpretation of viability provided by quantitative rest–4-hour ²⁰¹Tl analysis in only 4 (2%) of 219 persistent defects at 4 hours.

Regional Systolic Function at Rest and Contractile Reserve in Relation to ²⁰¹Tl Redistribution at 24 Hours
Of 134 mild to moderate persistent defects at 4 hours that remained unchanged at 24 hours, 58 (43%) showed normal function at rest, 35 (26%) were hypokinetic, and 41 (31%) were akinetic. Similarly, of 42 mild to moderate persistent defects at 4 hours that demonstrated 24-hour redistribution, 25 (60%) showed normal function at rest, 7 (17%) were hypokinetic, and 10 (23%) were akinetic (all P=NS versus mild to moderate defects without late redistribution; Fig 3). Among severe persistent defects at 4 hours, only 1 segment showed normal systolic function at rest. This segment demonstrated late redistribution at 24 hours. Of the remaining 3 segments with severe defects at 4 hours that showed partial redistribution at 24 hours, 2 were akinetic and 1 was hypokinetic.

View larger version (22K): [in this window] [in a new window]   Figure 3. Regional systolic function at rest by echocardiography in myocardial regions with persistent mild to moderate 201Tl defects at 4 hours with and without late redistribution at 24-hour imaging. The percent of regions with normal and abnormal systolic functions did not differ statistically between segments with and without late redistribution. LR+ indicates late redistribution; LR-, no late redistribution.

Normal function during dobutamine was observed in 100% and 86% of hypokinetic segments corresponding to mild to moderate defects at 4 hours with and without late redistribution, respectively. Similarly, the percent of akinetic segments that improved during dobutamine did not significantly differ between mild to moderate persistent defects at 4 hours with (1 [10%] of 10) and without late redistribution (14 [34%] of 41) (P=NS). The number of segments with severe ²⁰¹Tl defects and impaired function at rest that improved during dobutamine was very small (6 [14%] of 42; Table 3). Four of these segments corresponded to hypokinetic territories and 1 showed late redistribution at 24 hours, whereas of the remaining 2 akinetic segments that improved with dobutamine, 1 showed late (partial) redistribution.

Concordance and Discordance Between Scintigraphic and Echocardiographic Findings in Dysfunctional Segments
Of a total of 105 hypokinetic segments, 99 (94%) were judged viable by ²⁰¹Tl criteria. In all groups of ²⁰¹Tl segments, the majority of hypokinetic segments showed normalized function in response to dobutamine. In fact, of a total of 105 hypokinetic segments, 88 (84%) improved during dobutamine. Eighty-four (95%) of these had evidence of ²⁰¹Tl viability. Thus, concordant information about viability by ²⁰¹Tl findings and echocardiographic findings was obtained in 86 (82%) of 105 hypokinetic segments (=0.09; P=NS; Fig 4). Similarly to hypokinetic segments, 119 (77%) of 155 akinetic segments were determined to be viable by ²⁰¹Tl. Only 34 (22%) of 155 akinetic segments, however, improved during dobutamine. Evidence of ²⁰¹Tl viability was found in 32 (94%) of these 34 segments but also was found in 87 (72%) of 121 akinetic segments that did not improve during dobutamine. Thus, concordance between echocardiographic and ²⁰¹Tl findings was obtained in 66 (43%) of 155 akinetic segments (=0.12; P=NS; Figs 4, 5, and 6). When the effects of late redistribution were added to the analysis of rest–4-hour ²⁰¹Tl findings, the overall concordance (including all segments) between the two techniques did not change (from 79% to 80%), nor did concordance in akinetic segments alone (both 43%). Akinetic segments deemed to be viable by ²⁰¹Tl and that had contractile reserve were observed in 14 patients, whereas the presence of akinetic segments judged viable by ²⁰¹Tl but that did not have contractile reserve was observed in an additional 14 patients. The severity of coronary artery disease was different between the two groups: in the group with contractile reserve, 7 patients (50%) had single-vessel coronary artery disease and only 1 patient (7%) had three-vessel disease. In contrast, 7 patients (50%) in the latter group (viability by ²⁰¹Tl but not by contractile reserve) had three-vessel coronary artery disease, and 4 (29%) had single-vessel disease. Collaterals were present in 35% of patients with akinetic segments deemed viable by ²⁰¹Tl but without contractile reserve.

View larger version (14K): [in this window] [in a new window]   Figure 4. Concordance between contractile reserve by dobutamine (Dob) and metabolic viability by 201Tl in hypokinetic and akinetic myocardial regions. Dob+ indicates improved function with dobutamine; Dob-, unchanged function with dobutamine.

View larger version (82K): [in this window] [in a new window]   Figure 5. Example of an apical four-chamber view from a patient with a dilated left ventricle. Resting images (top) demonstrate akinesia of the apex and posterior septum. During dobutamine, no improvement of the akinetic territories is observed, whereas the lateral wall demonstrates hyperkinesia.

View larger version (75K): [in this window] [in a new window]   Figure 6. Short-axis 201Tl tomograms from the same patient as in Fig 5 illustrating preserved 201Tl uptake and hence viability at the septal level, where akinesia that did not improve during dobutamine was observed.

Postrevascularization Follow-up
Fifty-eight hypokinetic and 51 akinetic segments were revascularized in 18 patients. Improvement after revascularization was observed in 51 (88%) of the hypokinetic segments and in 22 (43%) of the akinetic segments. The probability of functional improvement after revascularization was linearly correlated to ²⁰¹Tl uptake at 4 hours (r=.95; P<.004; Table 2). Of the 109 dysfunctional segments that were revascularized, 34 (31%) exhibited a persistent mild to moderate defect at 4 hours, and late redistribution occurred in 9 (26%) of these segments. In the entire group of dysfunctional segments, dobutamine showed positive and negative predictive accuracies of 92% and 65%, respectively, with a sensitivity of 79% and a specificity of 83%. ²⁰¹Tl tomography demonstrated positive and negative predictive accuracies of 72% and 100%, respectively, with a sensitivity of 100% and a specificity of 22%. In akinetic segments alone, dobutamine echocardiography was 88% accurate in predicting functional improvement after revascularization and 76% accurate in predicting lack of improvement. Sensitivity and specificity for viable akinetic segments were 68% and 90%, respectively. In contrast, positive predictive accuracy was 51% for ²⁰¹Tl, with a negative accuracy of 100%. Sensitivity and specificity for ²⁰¹Tl were 100% and 28%, respectively.

Patients With Impaired Global Left Ventricular Function
In 18 patients with global ejection fraction at rest 45% (mean±SD, 37±7%), concordance between the two techniques was similar to that observed in the entire group of patients (91% in hypokinetic segments and 46% in akinetic segments). Eight patients with impaired global function were revascularized. A total of 59 dysfunctional (33 hypokinetic and 26 akinetic) segments were evaluated in these patients. Positive and negative predictive accuracies were 93% and 93%, respectively, for dobutamine and 60% and 100%, respectively, for ²⁰¹Tl. Sensitivity and specificity were 93% and 93%, respectively, for dobutamine and 100% and 25%, respectively, for ²⁰¹Tl. Global left ventricular ejection fraction after revascularization improved in 4 of 7 patients in whom it was measured, and it was associated with an improvement of preoperative dysfunctional segments in each of them. In contrast, the three patients with unchanged or worsened ejection fraction showed extensive akinetic territories before revascularization that remained mostly unchanged thereafter.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Impact of Late ²⁰¹Tl Redistribution on Evaluation of Myocardial Viability
In the present study, 21% of all persistent ²⁰¹Tl defects at 4 hours showed late redistribution at 24 hours, and 18% of segments with partial redistribution at 4 hours showed complete redistribution at late imaging. The frequency of late redistribution was higher in mild to moderate defects compared with severe defects, and at 4 hours, 91% of all defects that exhibited late redistribution were mild to moderate. As in the current evaluation of ²⁰¹Tl scintigraphy, a mild to moderate reduction of ²⁰¹Tl uptake indicates viability; late redistribution alone identified as viable four segments that exhibited a severe and persistent reduction of ²⁰¹Tl uptake at 4 hours. Thus, measurement of ²⁰¹Tl activity at 4 hours yielded appropriate viability information in 215 (98%) of all persistent defects. In addition, analyses of regional function and of contractile reserve did not show significant differences between segments with and without late redistribution (Fig 3, Table 3). It might be argued, however, that late redistribution might identify segments with a greater likelihood of improvement after revascularization. The small number of revascularized regions with mild to moderate defects with and without late redistribution does not allow us to establish this from the present data. Similarly, the potential impact on clinical decision making of severely hypoperfused and dysfunctional segments with late redistribution deserves further investigation.

Regional Systolic Function in Relation to Rest–4-Hour ²⁰¹Tl Uptake
The majority of segments (66%) with normal ²⁰¹Tl uptake at rest showed normal function, although in a sizable number of these segments, systolic function was impaired (Fig 1, Table 1), as reported previously.^{5 14 20 21} Several hypotheses can be offered to explain this finding: (1) blood flow by positron emission tomography has been reported to be normal in segments with impaired function at rest in patients with chronic coronary artery disease,^{22 23} and it has been interpreted to reflect the admixture of normally perfused and necrotic myocardium²³ ; (2) although no patients reported angina at the time of the present study, the possibility of silent ischemia leading to stunning myocardium at the time of ²⁰¹Tl imaging cannot be ruled out; and (3) impaired function in normally perfused segments may be the result of the interaction of dysfunctional and adjacent normal myocardium.^{24 25} Finally, a potential misalignment between ²⁰¹Tl and echocardiographic segments may also account for impaired function shown by normally perfused segments.

Normal systolic function at rest was also observed in about half of the segments with reversible ²⁰¹Tl defects and in 47% of the segments with a mild to moderate persistent defect at 4-hour redistribution, consistent with previous observations.¹⁴ In contrast, normal function was observed in only one of the segments with a severe persistent defect, and in this group, the majority of segments was akinetic at rest, indicating that these territories predominantly consist of necrotic myocardium.

Contractile Reserve in Relation to ²⁰¹Tl Findings
The percent of dysfunctional segments that improved with dobutamine was significantly higher among those with ²⁰¹Tl uptake 50% of maximal compared with segments that exhibited severe persistent defects (Fig 2). However, although ²⁰¹Tl uptake 50% of maximal is considered representative of viability, only half of such segments showed contractile reserve. The discordance between viability by ²⁰¹Tl and contractile reserve was primarily observed in akinetic segments. In fact, in the present study, 94% and 77% of hypokinetic and akinetic segments, respectively, were deemed viable by ²⁰¹Tl criteria, consistent with previous observations.^{5 26} However, although 85% of hypokinetic segments showing ²⁰¹Tl viability also improved with dobutamine, only 27% of akinetic segments showing ²⁰¹Tl viability did so. Evidence of viability by positron emission tomography but not by dobutamine echocardiography in akinetic segments was observed by Baer et al.²⁷ More recently, Panza et al²¹ reported an overall concordance of 68% between transesophageal dobutamine echocardiography and exercise-redistribution-reinjection ²⁰¹Tl tomography in dysfunctional segments of patients with ventricular dysfunction, similar to the 58% concordance observed in the current study in dysfunctional segments.

In revascularized patients, positive predictive accuracy for functional recovery was 92% for dobutamine and 72% for ²⁰¹Tl, whereas negative accuracy was 65% and 100%, respectively. Of note, when only akinetic segments were included in the analysis, positive accuracy for ²⁰¹Tl decreased substantially, to 51%. Because of the high number of segments identified as viable, sensitivity for ²⁰¹Tl was very high but at the expense of low specificity. Consistent with the current findings, Ragosta et al⁵ reported a positive predictive accuracy for functional recovery of 57% in severely dysfunctional segments using planar rest-redistribution imaging, with a negative accuracy of 23%. More recently, Udelson et al⁷ reported a positive accuracy of 75% and a negative accuracy of 92% using tomographic rest-redistribution imaging. In contrast, previous studies reported higher positive accuracy using the stress-redistribution²⁸ or the reinjection protocol.²⁹ Differences in the study population, degree of global left ventricular impairment, number of revascularized segments, type of imaging, and degree of resting regional dysfunction may account for this discrepancy. Therefore, it is important to compare different techniques in the same patients. In this regard, Arnese et al,³⁰ who compared dobutamine echocardiography with ²⁰¹Tl reinjection in patients with impaired left ventricular function, also demonstrated reduced positive accuracy and specificity of ²⁰¹Tl in predicting recovery of function.

Conceivably, many explanations may account for the discordance between metabolic and functional indexes of viability. ²⁰¹Tl scintigraphy detects metabolic viability, ie, the presence of residual intact cells capable of retaining the injected tracer. However, there is no direct correlation between the amount of ²⁰¹Tl uptake and either the amount of residual viable cells or their transmural distribution, which directly influences systolic function.^{31 32} Actually, it is conceivable that in a dysfunctional segment, viable cells may be present but insufficient to affect function. Moreover, it is also conceivable that dysfunctional segments with mild to moderate persistent defects consist of an admixture of normally perfused viable and necrotic myocardium. In these segments, no functional improvement can be expected despite evidence of viability. In addition, contractile and coronary reserves may be exhausted in some severely dysfunctional yet metabolically viable segments. In that case, the segments would not be capable of facing the increased oxygen demand imposed by inotropic stimulation³³ and could only improve after the amelioration of perfusion. This hypothesis is supported by the findings of 35% of dysfunctional segments without contractile reserve that improved after revascularization and the lack of collaterals in the majority of patients with akinetic segments deemed viable by ²⁰¹Tl but without contractile reserve. In addition, subtle functional improvement during dobutamine in dysfunctional segments may be undetected by visual echocardiographic analysis. Finally, some misalignment between echocardiographic and scintigraphic segments is expected and may have contributed to the observed discrepancy.

Study Limitations
Regional ²⁰¹Tl uptake was not compared with a normal database, and a single threshold value was used to define abnormal uptake. This might have led to a misclassification of some myocardial regions among the groups of viable ²⁰¹Tl regions. However, because all ²⁰¹Tl regions with an uptake 50% of maximal activity were considered together as viable regions in the comparison with dobutamine, this potential misclassification has no effect on the concordance between ²⁰¹Tl and dobutamine or on the accuracy of ²⁰¹Tl in predicting the effects of revascularization. Global left ventricular function was preserved in many patients. Thus, the current study group does not strictly represent patients with depressed left ventricular function, in whom identification of viability is more critical. Therefore, larger studies are warranted to verify whether the current findings hold true in patients with severely impaired global function. The body size of the current population is mainly representative of a European population and, therefore, the results obtained may not apply entirely to populations with a larger body size. Finally, because dobutamine echocardiography has been evaluated against the "gold standard" of functional recovery assessed by echocardiography, misregistration presumably has a reduced impact on the echocardiographic technique compared with ²⁰¹Tl, and this might have influenced the accuracy of the two techniques in predicting the effects of revascularization.

Conclusions
Late ²⁰¹Tl redistribution after resting injection occurs in 20% of persistent defects at 4 hours and is more common in segments that exhibit a mild to moderate persistent defect. Late redistribution does not identify segments with more preserved systolic function or contractile reserve. In the majority of myocardial segments with severely impaired function at rest, contractile reserve is not present despite evidence of metabolic activity by ²⁰¹Tl analysis. Therefore, ²⁰¹Tl scintigraphy and dobutamine echocardiography provide discordant information regarding viability in these territories. In a relatively small number of revascularized dysfunctional segments, dobutamine echocardiography resulted in higher positive accuracy, indicating an overestimation for functional recovery by ²⁰¹Tl. In contrast, ²⁰¹Tl tomography demonstrated higher sensitivity and negative predictive accuracy than dobutamine.

	Footnotes

 
Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994, and published in abstract form (Circulation. 1994;90[part 2]:I-314).

Received November 27, 1995; revision received September 6, 1996; accepted September 9, 1996.

	References

Top Abstract Introduction Methods Results Discussion References

 
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