Assessment of Myocardial Viability With 99mTc-Sestamibi Tomography Before Coronary Bypass Graft Surgery
Correlation With Histopathology and Postoperative Improvement in Cardiac Function
Background Assessment of myocardial viability by 99mTc-sestamibi remains controversial. Accordingly, we investigated the use of sestamibi as a marker of myocardial viability, defined by histopathology, and for predicting improvement of myocardial function after coronary artery bypass graft surgery (CABG).
Methods and Results 99mTc-sestamibi perfusion tomography and radionuclide angiography were performed within 2 days before CABG in 21 patients with ≥75% stenosis of the left anterior descending coronary artery and resting anterior wall dyssynergy. During CABG, transmural myocardial biopsies were obtained from the dyssynergic anterior wall and from normal myocardial segments to determine the extent of viable myocardium by histopathology. Improvement of regional left ventricular function was evaluated by radionuclide angiography at 6 to 8 weeks after CABG. There was a good correlation (r=.85, P<.001) between the quantified sestamibi activity and the extent of viable myocardium determined morphometrically. Among 21 biopsied dyssynergic myocardial segments, 11 improved their function after CABG and 10 failed to improve. Biopsied segments with improved postoperative function had significantly higher sestamibi activity (81±5% versus 49±16%, P<.0001) and significantly lower extent of interstitial fibrosis (7±4% versus 31±21%, P=.0002) than segments that failed to improve. A 55% threshold of 99mTc-sestamibi activity had positive and negative predictive values of 79% and 100%, respectively, for recovery of function after CABG in the biopsied segments.
Conclusions Myocardial 99mTc-sestamibi activity correlates well with the extent of viable myocardium and predicts improvement in regional function after CABG. This lends support to the use of sestamibi as a myocardial viability agent.
Assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function plays an important role in the decision to refer these patients for coronary revascularization. Patients with depressed ventricular function on the basis of chronic hibernation of otherwise viable myocardium may improve their systolic performance if the myocardial blood flow is improved by CABG.1 2 However, both the morbidity and the mortality of CABG in these patients increase as the LVEF decreases. Thus, assessment of the potential benefits, which we hope will outweigh the risk of revascularization, becomes essential.
PET is considered by some to be the gold standard to ascertain the presence of myocardial viability.3 4 5 However, it has not achieved widespread usage because of its relatively high cost and consequent limited availability. Heretofore, 201Tl has been considered the preferred agent to detect viable myocardium, with one of several possible imaging strategies, such as rest-redistribution,6 7 8 late redistribution,9 10 or rest-reinjection protocols.11 12 13 Recently, 99mTc-sestamibi has also been investigated as a potential viability marker; initial studies have shown good concordance between 201Tl and 99mTc-sestamibi activities in both viable and nonviable myocardium.14 15 16 Moreover, 99mTc-sestamibi activity has been found to be a good predictor of functional recovery after coronary revascularization.14 To date, however, there have been no studies validating the criteria of myocardial viability that were derived from 99mTc-sestamibi imaging against histopathological findings. Hence, this study was designed to investigate the relationship between myocardial 99mTc-sestamibi activity and the extent of viable myocardium in patients with coronary artery disease. In addition, we investigated the ability of 99mTc-sestamibi SPECT to predict recovery of left ventricular function after CABG.
The study population consisted of 21 patients with chronic stable angina, resting anterior wall dyssynergy, and ≥75% stenosis of the LAD who were scheduled to undergo CABG. The decision to recommend CABG originated entirely with the patient’s attending cardiologist and cardiac surgeon. In no case did the results of this investigation result in a change in the planned treatment. 99mTc-sestamibi SPECT and radionuclide angiography were performed within 2 days before CABG to assess the extent of perfusion and contraction abnormalities. Radionuclide angiography was repeated 6 to 8 weeks after CABG to ascertain improvement in regional ventricular function. During CABG, transmural myocardial biopsies were obtained from the dyssynergic anterior wall and from normal myocardial segments to determine the extent of viable myocardium and interstitial fibrosis.
Radionuclide angiography was performed as previously reported from our laboratory.17 Patients were injected with 5.0 mg of stannous sodium pyrophosphate followed by 20 mCi of [99mTc]pertechnetate and imaged in the anterior, 30° left anterior oblique, and 70° left anterior oblique projections. The LVEF was calculated from the images obtained in the 30° left anterior oblique view with a semiautomatic software previously validated in our laboratory.17 For segmental wall motion analysis, the left ventricle was divided into 10 segments as shown in Fig 1⇓. The wall motion was visually graded on each segment on a score ranging from 0 to 4, where 4 denoted normal, 3 mild hypokinesis, 2 moderate hypokinesis, 1 severe hypokinesis, and 0 akinesis or dyskinesis. The pre- and post-CABG radionuclide angiography studies were processed and analyzed by an experienced investigator who was unaware of the timing of the studies and all clinical, scintigraphic, and surgical information.
99mTc-Sestamibi SPECT Imaging
After the patient had fasted overnight, 25 mCi of 99mTc-sestamibi was injected at rest, and image acquisition began 60 minutes later. SPECT imaging and processing were done with techniques previously reported from our laboratory.18
For qualitative analysis of regional myocardial perfusion, the left ventricle was divided into 10 segments to match the myocardial segments on the radionuclide angiograms. Two short-axis tomographic slices were analyzed: one located halfway between the midportion of the left ventricular cavity and the uppermost basal slice, and the other between the midcavity and the lowermost apical slice. The left ventricular apex was analyzed from one vertical long-axis slice through the mid-portion of the left ventricular cavity. 99mTc-sestamibi activity in each segment was qualitatively graded on a score ranging from 0 to 4, where 4 denoted normal activity, 3 mildly decreased, 2 moderately decreased, 1 severely decreased, and 0 absent tracer activity.
In addition to the qualitative assessment of myocardial tracer activity, quantitative determination of perfusion defect size and regional 99mTc-sestamibi uptake was performed on computer-generated polar maps as previously reported from our laboratory.18 Briefly, a circumferential profile analysis is first applied to each tomographic slice in the short axis. The normalized short-axis profiles are then displayed in the polar map as concentric rings, with the basal slices represented as the outermost and the apical slices the innermost rings. The apical limits are defined from the short and vertical long axis and displayed in the center of the polar map. The polar map of each individual patient is then statistically compared on a pixel-by-pixel basis with a 99mTc-sestamibi normal data bank derived from 50 normal subjects. Pixels with a tracer activity <2.5 SD below the corresponding normal mean values were considered abnormal. Perfusion defect size was computed as the number of abnormal pixels divided by the total number of pixels encompassing the whole left ventricle×100. Regional 99mTc-sestamibi activity was measured from a region of interest (5×5 pixels) placed in each of the 10 segments analyzed, and the tracer activity was computed as percent of the maximal myocardial activity.
Transmural Left Ventricular Biopsies and Morphometric Analysis
Transmural myocardial biopsies were obtained with a 20-mm, 14-gauge Tru-Cut biopsy needle (Travenol Laboratories) at the time of CABG, after initiation of cardiopulmonary bypass but before administration of cardioplegic solution. The biopsies were always obtained from the dyssynergic anterior wall, in the region between the LAD and its first or second diagonal branch. In 5 patients, a second biopsy (control) was taken from a normally contracting lateral wall perfused by an angiographically normal circumflex artery.
The myocardial specimens were immediately fixed in 10% buffered formalin, processed through exposure to a graded series of ethanol solutions, embedded in paraffin, and finally cut serially into sections 3 μm thick. These tissue sections were then stained with hematoxylin-eosin and Mallory’s trichrome to identify the extent of fibrosis. The area of fibrosis, which stained purple on trichrome stain, was readily distinguished from viable myocardium, which stained pink. The extent of fibrosis on each of the sections was determined with a computer image analysis technique using Optima Bioscan software and expressed as percent of the total myocardium examined on each section, as previously described.19 The extent of viable myocardium was then determined as 100% minus % fibrosis.
Continuous data are expressed as mean±SD. Student’s t test or ANOVA was used as appropriate to compare continuous data. Correlation between percent 99mTc-sestamibi activity and percent viable myocardium was performed by least-squares linear regression analysis.
Twenty-one patients (19 men, 2 women; mean age, 63±10 years) were enrolled in the study (Table 1⇓). Thirteen patients had a history of prior anterior wall myocardial infarction. The mean LAD luminal diameter stenosis was 94±8%, and 10 patients had a completely occluded artery. All patients had multivessel disease and underwent complete revascularization consisting of 2 to 4 grafts per patient (mean, 2.9). All LAD stenoses were bypassed with a left internal mammary artery graft, except for 3 patients who received saphenous vein grafts at the surgeon’s discretion. All other arteries were bypassed with saphenous vein grafts. None of the patients developed ECG evidence of perioperative myocardial infarction.
The mean preoperative LVEF was 41±13%, and 12 patients had an LVEF <40%. The mean resting 99mTc-sestamibi SPECT defect size was 20±18% of the left ventricle.
Relation Between Myocardial Viability, Regional Function, and Perfusion
Twenty-six myocardial samples underwent microscopic studies. These 26 segments were divided into three groups on the basis of the preoperative wall motion score: group A, segments with severe hypokinesis or akinesis (wall motion scores of 0 or 1, n=12); group B, segments with mild to moderate hypokinesis (scores of 2 or 3, n=9); and group C, segments with normal wall motion (score of 4, n=5). The mean percent fibrosis in these three groups was 23±18%, 13±8%, and 6±2%, respectively (P=.04 by ANOVA).
The percent fibrosis was also analyzed with respect to the preoperative qualitative perfusion scores. On the basis of these scores, the 26 biopsied segments were segregated into three groups: group I, segments with severely decreased or absent perfusion (scores of 0 or 1, n=3); group II, segments with mildly to moderately decreased perfusion (scores of 2 or 3, n=10); and group III, segments with normal perfusion (score of 4, n=13). The mean percent fibrosis in these groups was 44±16%, 17±12%, and 9±7%, respectively (P<.001).
Quantitative assessment of the SPECT images showed a strong correlation between the percent sestamibi activity and percent of histologically viable myocardium (Fig 2⇓), with a correlation coefficient of .85 (P<.001). Seven of the total 26 biopsied segments had <55% 99mTc-sestamibi uptake, and all of these segments had >20% fibrosis. In contrast, only 2 segments of the remaining 19 biopsied segments with ≥55% 99mTc-sestamibi uptake had >20% fibrosis. The mean percent fibrosis in segments with <55% and ≥55% sestamibi uptake was 35±13% and 9±7%, respectively (P=.002).
All of the 21 dyssynergic biopsied segments were supplied by a severely stenotic LAD (of which 10 were totally occluded). There was no significant correlation between the percent LAD stenosis and the percent sestamibi uptake in the dyssynergic anterior segments (r=.37, P=.10). Likewise, there was a poor correlation between the percent LAD stenosis and the percent of myocardial fibrosis in those segments (r=.33, P=.15). The 10 anterior segments supplied by a totally occluded artery tended to have a lower percent sestamibi uptake (58±24%) and more percent fibrosis (23±15%) than those segments supplied by a patent artery (71±15% and 17±15%, respectively), but these differences did not reach statistical significance (P=.18 and P=.38, respectively).
Prediction of Postoperative Improvement in Regional Ventricular Function
The mean LVEF improved modestly after CABG (from 41±13% to 45±12%), but the difference did not reach statistical significance (P=.07).
The postoperative improvement in regional function was significantly dependent on the extent of viable myocardium (Fig 3⇓). As such, the wall motion score after CABG improved by ≥1 grade in 11 of the 21 anterior wall segments biopsied. These improved segments had significantly less fibrosis than the 10 segments without functional improvement (7±4% versus 31±12%, P=.0002). The postoperative improvement in function was also significantly related to the preoperative myocardial sestamibi activity (Fig 3⇓). The mean sestamibi activity was 81±5% in segments with improved function, compared with 49±16% in those without functional improvement (P=.0001).
The correlation between 99mTc-sestamibi activity and the postoperative improvement in function was also significant when all 210 left ventricular segments available for interpretation were assessed (Fig 4⇓). Among the 85 segments with abnormal wall motion before surgery (excluding the septal segments to avoid the surgically induced septal motion abnormalities), 28 improved their wall motion by ≥2 grades after surgery, 27 had 1 grade improvement, and 30 had no improvement. Segments with ≥2 grades improvement in wall motion and segments that improved by only 1 grade had similar 99mTc-sestamibi activity (72±17% versus 70±21%, P=.73). Segments with no improvement in function, however, had a significantly lower sestamibi activity than segments that improved by 1 grade (55±20% versus 70±21%, P=.009). Fig 5⇓ illustrates an example of a patient who had postoperative improvement of anterior wall function, with the corresponding scintigraphic and histological findings.
The positive and negative predictive values of 99mTc-sestamibi SPECT for recovery of regional function after CABG were determined at various thresholds of 99mTc-sestamibi activity. The thresholds and corresponding positive and negative predictive values are shown in Table 2⇓. The threshold with the best accuracy was that of a 55% sestamibi activity, which had positive and negative predictive values of 75% (45 of 60 segments) and 60% (15 of 25 segments), respectively. Ten dyssynergic segments had improved postoperative function, despite having <55% sestamibi uptake before CABG. Nine of these segments involved the inferior wall.
By restricting the analysis to only the dyssynergic anterior segments (n=47), we found positive and negative predictive values of 79% (31 of 39 segments) and 88% (7 of 8 segments), respectively, for a 55% sestamibi activity threshold. In contrast, separate analysis of only the dyssynergic inferior segments (n=38) showed positive and negative predictive values of 67% (14 of 21 segments) and 47% (8 of 17 segments), respectively, for the same 55% threshold. When the analysis was restricted to only the dyssynergic anterior segments that were the sites of biopsy, the 55% sestamibi uptake cutoff had positive and negative predictive values of 79% (11 of 14 segments) and 100% (7 of 7 segments), respectively.
Fourteen segments among the 21 biopsied dyssynergic anterior segments had ≥55% sestamibi uptake. Eleven of these 14 segments showed improved function after surgery and 3 did not. All of the 11 segments with improved function after surgery had <20% fibrosis. The 3 segments that failed to improve had 17%, 24%, and 27% fibrosis, respectively.
Assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function plays an important role in the decision to refer these patients for coronary revascularization. Thus far, 201Tl has been the preferred tracer to assess myocardial viability, in large part because of its ability to redistribute. Earlier studies suggested that 99mTc-sestamibi was not a good viability agent.20 21 However, a substantial body of evidence now indicates that 99mTc-sestamibi may also be a good viability marker.14 15 16 In addition, experimental studies have shown that mitochondrial function and sarcolemmal integrity are crucial for the uptake and retention of 99mTc-sestamibi,22 23 24 thus establishing a link between the tracer kinetics, preserved myocardial metabolism, and myocyte viability.
Our study demonstrates a close correlation between 99mTc-sestamibi activity and the extent of histologically documented myocardial viability in patients referred for CABG. Because a preserved cellular structure is the ultimate proof of viability, our results lend support to the use of 99mTc-sestamibi as a viability marker. In a recently reported study19 using explanted hearts from transplant recipients, we were able to show a good linear correlation (r=.89, P<.001) between the extent of scintigraphic scar quantified by 99mTc-sestamibi SPECT and the actual pathological scar size. In addition, the actual myocardial 99mTc-sestamibi activity correlated well (r=.90, P<.0001) with the extent of myocardial viability determined histologically.
In most previous publications, myocardial viability has been defined on the basis of an improvement in wall motion after CABG. By such a definition, arbitrary cutoffs for myocardial tracer activity (usually 50% to 60%) have been found to be the best radionuclide predictor of viability, albeit with only a moderate positive predictive value (50% to 70%). In the present study, however, we have demonstrated that 99mTc is a better marker of myocardial viability than one would conclude solely by comparing sestamibi activity with the recovery of regional ventricular function after CABG. The extent of hypoperfused myocardium that is histologically normal, although hypoperfused, will determine whether or not wall motion will improve after CABG. For example, a 50% reduction in 99mTc-sestamibi tracer uptake in a given myocardial segment could theoretically be produced either by a 50% transmural reduction in myocardial flow across the left ventricular wall containing viable, histologically normal myocardium or alternatively, by a combination of fibrosis in the 50% endocardial half of the wall and normal perfusion in the 50% epicardial half of the wall. In the former scenario, the wall motion would be expected to improve after CABG, whereas in the latter scenario, the wall motion is not likely to improve after CABG. However, as evidenced by our negative predictive value of 60% for a cutoff threshold of 55% sestamibi activity, several segments with <55% activity did show improved function after surgery. This observation suggests that it is indeed possible for segments to be hypoperfused, to have low tracer uptake, but yet to be viable and recover after revascularization. Alternatively, photon attenuation may lead to underestimation of myocardial viability. In fact, our separate analysis of the 10 segments with <55% sestamibi uptake that nevertheless had improved postoperative function showed that 9 of them involved the inferior wall, a region in which photon attenuation has a greater impact. Although we explored different thresholds for inferior defects (Table 2⇑), we could not identify a single threshold of sestamibi activity that yielded robust predictive values in this region. This is probably because photon attenuation in the inferior wall is not predictable but varies from patient to patient. Attenuation correction may be essential to further enhance the value of perfusion imaging for viability detection in inferior wall segments.
Udelson et al14 compared rest-redistribution 201Tl and 99mTc-sestamibi for predicting recovery of function after coronary revascularization. They found a significant correlation (r=.86) between the regional activity of 201Tl in the redistribution images and 99mTc-sestamibi activity. It is interesting to note that the percent sestamibi activity in the segments with reversible dysfunction (75±9%) and those with irreversible dysfunction (50±8%) in Udelson’s study were similar to the values we found in our study (71±12% and 55±20%, respectively). The negative predictive value for improvement in wall motion, however, was higher in Udelson’s study. This difference can probably be ascribed to differences in study design. In another study, Kauffman et al16 reported similar 99mTc-sestamibi and delayed 201Tl activities in mild (67.7±12.4% versus 66.9±9.1%) as well as severe (44.5±11.3% versus 42.9±8.6%) defects. Dilsizian et al15 also compared results of stress-redistribution-reinjection 201Tl SPECT with 99mTc-sestamibi SPECT and found a 93% concordance rate when the regional activities of the two tracers were quantified.
Zimmerman et al25 used planar scintigraphy to evaluate the relation between 201Tl activity and myocardial fibrosis by obtaining transmyocardial biopsies during CABG. A significant correlation (r=−.62, P=.03) was found between the 201Tl activity in the redistribution images and the extent of interstitial fibrosis. This correlation improved further (r=−.85) when the extent of interstitial fibrosis was compared with the 201Tl activity determined after reinjection. Thus, both 99mTc-sestamibi and 201Tl activity exhibit a similar relationship with the extent of myocardial viability.
Recently, Maes et al26 investigated the use of 99mTc-sestamibi for assessing myocardial viability in patients undergoing CABG. A linear correlation (r=−.78) was found between sestamibi uptake and percent fibrosis in the biopsy specimens of the dyssynergic ventricular wall. In this study, the amount of myocardial fibrosis was estimated by means of a calibrating grid coupled to the light microscope. A similar correlation (r=−.79) was found by these authors between tracer uptake assessed by [13N]ammonia PET and the percent of myocardial fibrosis. 99mTc-sestamibi uptake was significantly higher in areas considered viable by [18F]fluorodeoxyglucose and in regions with improved regional contraction after CABG. These results are in agreement with ours. The better correlation between sestamibi uptake and percent fibrosis in our study may be ascribed to the probably more accurate determination of percent myocardial fibrosis, which in our study used a computer-assisted light microscopy technique. Maes et al26 also reported a higher negative predictive value for a 50% threshold cutoff of sestamibi uptake (78%). However, only segments undergoing a biopsy were included in their calculations. When we calculated the predictive value in our cohort using only anterior wall segments that were biopsied, we found a negative predictive value of 100% (7 of 7 segments) and a positive predictive value of 79% (11 of 14 segments). Thus, it appears that a more robust accuracy can be attained when one investigates solely the dyssynergic anterior wall segments instead of all dyssynergic segments. The well-known effect of photon attenuation, which has a greater impact in inferior defects and leads to underestimation of myocardial viability in this region,27 28 could, in part, explain these observations. It is also conceivable that administration of nitroglycerin before the injection of sestamibi might have further enhanced the correlation between sestamibi activity levels and extent of myocardial viability.29 30
A limitation of our study is that only one biopsy was obtained from the dyssynergic segments in each patient. One could question whether this sample was representative of the whole segment, in terms of the extent of myocardial fibrosis. Although one would have liked to obtain a larger number of biopsies, the decision to obtain only one biopsy from each segment was based on patient safety considerations. In the study by Zimmerman et al,25 two biopsies were obtained per patient. These investigators showed a good reproducibility between the two specimens. Maes et al26 also obtained only a single biopsy from each patient. Another limitation of our study is that relatively few segments with <60% viable myocardium were biopsied and thus the correlation between percent sestamibi activity and percent viable myocardium in these segments is not as clearly defined as in those with >60% viable myocardium. However, in a previous report from our laboratory,19 using biopsies from explanted hearts of transplant recipients, we were able to show a good correlation (r=.90, P<.0001) between the percent sestamibi activity measured by well counting and the percent viable myocardium over a wide range of values (from 5% to 100% viable myocardium), including 15 segments with <50% viable myocardium.
In our study, we elected to assess left ventricular function by radionuclide angiography because of the well-known accuracy and reproducibility of this technique. Unfortunately, this precluded evaluation of wall thickening, which is also an important parameter of regional ventricular function that could have been evaluated by either echocardiography or gated-SPECT imaging. A further limitation is that we assessed the left ventricular function at only one time after CABG (6 to 8 weeks). Repeat follow-up studies might have shown further delayed improvement in ventricular function.31
In conclusion, our data provide support for the use of 99mTc-sestamibi to evaluate the likelihood of dyssynergic myocardial segments to improve function after CABG. Moreover, on the basis of the high correlation between 99mTc-sestamibi activity and the extent of histologically viable myocardium, our study conclusively demonstrates that this tracer is indeed a good marker of myocardial viability, better in fact than one would anticipate solely on the basis of the reversibility of abnormal wall motion abnormalities after CABG.
Selected Abbreviations and Acronyms
|CABG||=||coronary artery bypass graft surgery|
|LAD||=||left anterior descending coronary artery|
|LVEF||=||left ventricular ejection fraction|
|SPECT||=||single photon emission computed tomography|
Support for this study was provided by the 1994 Du Pont Pharma/Society of Nuclear Medicine Fellowship Award (Dr Dakik). The authors thank cardiovascular surgeons Joseph S. Coselli, MD, and Michael J. Reardon, MD, who assisted in providing some of the biopsies, and Anna Bravo for her secretarial assistance in preparing the manuscript.
Guest editor for this article was Barry L. Zaret, MD, Yale University Medical School, New Haven, Conn.
- Received March 10, 1997.
- Revision received June 3, 1997.
- Accepted June 14, 1997.
- Copyright © 1997 by American Heart Association
Schelbert H. Metabolic imaging to assess myocardial viability. J Nucl Med. 1994;35(suppl):8S-14S.
Bonow RO, Berman DS, Gibbons RJ, Johnson LL, Rumberger JA, Schwaiger M, Wackers FJ. Cardiac positron emission tomography: a report for health professionals from the Committee on Advanced Cardiac Imaging and Technology of the Council on Clinical Cardiology, American Heart Association. Circulation. 1991;84:447-454.
Ragosta M, Beller GA, Watson DD, Kaul S, Gimple LW. Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary artery bypass surgery in patients with severely depressed left ventricular function. Circulation. 1993;87:1630-1641.
Berger BC, Watson DD, Burwell LR, Crosby IK, Wellons HA, Teates CD, Beller GA. Redistribution of thallium at rest in patients with stable and unstable angina and the effect of coronary artery bypass surgery. Circulation. 1979;60:1114-1125.
Bonow RO, Dilsizian V, Cuocolo A, Bacharach SL. Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction: comparison of thallium scintigraphy with reinjection and PET imaging with 18F-fluorodeoxyglucose. Circulation. 1991;83:26-37.
Dilsizian V, Perrone-Filardi P, Arrighi JA, Bacharach SL, Quyyumi AA, Freedman NM, Bonow RO. Concordance and discordance between stress-redistribution-reinjection and rest-redistribution thallium imaging for assessing viable myocardium: comparison with metabolic activity by positron emission tomography. Circulation. 1993;88:941-952.
Udelson JE, Coleman PS, Metherall J, Pandian NG, Gomez AR, Griffith JL, Shea NL, Oates E, Konstam MA. Predicting recovery of severe regional ventricular dysfunction: comparison of resting scintigraphy with 201Tl and 99mTc sestamibi. Circulation. 1994;89:2552-2561.
Dilsizian V, Arrighi JA, Diodati JG, Quyyumi AA, Alavi K, Bacharach SL, Marin-Neto JA, Katsiyiannis PT, Bonow RO. Myocardial viability in patients with chronic coronary artery disease: comparison of 99mTc-sestamibi with thallium reinjection and [18F]fluorodeoxyglucose. Circulation. 1994;89:578-587.
Kauffman GJ, Boyne TS, Watson DD, Smith WH, Beller GA. Comparison of rest thallium-201 imaging and rest technetium-99m sestamibi imaging for assessment of myocardial viability in patients with coronary artery disease and severe left ventricular dysfunction. J Am Coll Cardiol. 1996;27:1592-1597.
Verani MS, Gaeta J, LeBlanc AD, Poliner LR, Phillips L, Lacy JL, Thornby JI, Roberts R. Validation of left ventricular volume measurements by radionuclide angiography. J Nucl Med. 1985;26:1394-1401.
Verani MS, Jeroudi MO, Mahmarian JJ, Boyce TM, Borges-Neto S, Patel B, Bolli R. Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile. J Am Coll Cardiol. 1988;12:1573-1581.
Medrano R, Lowry RW, Young JB, Weilbaecher DG, Michael LH, Afridi I, He ZX, Mahmarian JJ, Verani MS. Assessment of myocardial viability with 99mTc-sestamibi in patients undergoing cardiac transplantation: a scintigraphic/pathologic study. Circulation. 1996;94:1010-1017.
Marzullo P, Sambuceti G, Parodi O. The role of sestamibi scintigraphy in the radioisotopic assessment of myocardial viability. J Nucl Med. 1992;33:1925-1930.
Cuocolo A, Pace L, Ricciardelli B, Chiariello M, Trimarco B, Salvatore M. Identification of viable myocardium in patients with chronic coronary artery disease: comparison of thallium-201 scintigraphy with reinjection and technetium-99m methoxyisobutyl isonitrile. J Nucl Med. 1992;33:505-511.
Beanlands RS, Dawood F, Wen WH, McLaughlin PR, Butany J, D’Amato G, Liu PP. Are the kinetics of technetium-99m methoxyisobutyl isonitrile affected by cell metabolism and viability? Circulation. 1990;82:1802-1814.
Okada RD, Glover D, Gaffney T, Williams S. Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile. Circulation. 1988;77:491-498.
Zimmermann R, Mall G, Rauch B, Zimmer G, Gabel M, Zehelein J, Bubeck B, Tillmanns H, Hagl S, Kubler W. Residual 201Tl activity in irreversible defects as a marker of myocardial viability: clinicopathological study. Circulation. 1995;91:1016-1021.
Maes AF, Borgers M, Flameng W, Nuyts JL, van de Werf F, Ausma JJ, Sergeant P, Mortelmans LA. Assessment of myocardial viability in chronic coronary artery disease using technetium-99m sestamibi SPECT: correlation with histologic and positron emission tomographic studies and functional follow-up. J Am Coll Cardiol. 1997;29:62-68.
He ZX, Medrano R, Hays JT, Mahmarian JJ, Verani MS. Nitroglycerin-augmented 201Tl reinjection enhances detection of reversible myocardial hypoperfusion: a randomized, double-blind, parallel, placebo-controlled trial. Circulation. 1997;95:1799-1805.
Vanoverschelde JLJ, Wijns W, Borgers M, Heyndrickx G, Depré C, Flameng W, Melin JA. Chronic myocardial hibernation in humans: from bedside to bench. Circulation. 1997;95:1961-1971.