Technetium-99m-Sestamibi Imaging with Nitrate Infusion to Detect Viable Hibernating Myocardium and Predict Postrevascularization Recovery

Gianni Bisi, Roberto Sciagnà ,Giovanni M. Santoro, Vania Rossi and Pier Filippo Fazzini

Nuclear Medicine Unit, Department of Clinical Pathophysiology, University of Florence; and Division of Cardiology, Careggi Hospital; Florence, Italy

well-known relation between recognition of myocandial vi Wetestedtherelationshipof nitrate-inducedchangesin @‘Tcability in asynergic areas and postrevasculanization im sestamibi perfusiontomography and first-pass radionuclidean provement. The most accurate way to identify hibernating giocardiography (FPRNA)with postrevascularizationfunctional myocardium is to demonstrate a perfusion/metabolism mis recovery of asynergic territories. Methods: Twenty-eight pa match (preserved glucose uptake in severely hypoperfused tients, all with prior infarction and left ventricular dysfunction, tissue) by means of PET (3). Also recognition of 201T1 underwent two @‘@‘Tc-sestamibirest studies: one under base uptake is considered to be a reliable method for detecting line conditions and the other with nitrate infusion.The baseline hibernating myocardium and, because of the limited avail study was repeated after revascularization.Changes in global ability of PET facilities, it is the most widely used approach and regional perfusion and ventricularfunction were evaluated by perfusiontomography and FPRNA.Hibernatingmyocardium (4—7). was identifiedby functionalrecoveryin postrevascularization According to most experimental data, 99mTc@sestamibi FPRNA.Results: Elevenpatients and 31 segments in 19 coro has favorable features for use as a viability tracer (8—15), nary territories had functional recovery.Nitrate-inducedFPRNA but several human studies have shown that it may under changes showed poor agreement with postrevascularization estimate viable hibernating myocardium (16—20).The fac modifications: kappa = 0.24, ns, for the global and kappa = tons contributing to impaired @mTc@sestamibiuptake in 0.32, p < 0.01 for regional function. The agreement between hibernating myocardium are probably flow dependency of nitrate-induced and postrevascularization perfusion changes tracer uptake (10—12,14,21,22), relatively low extraction wasgoodbothconsiderIngthepatients(k= 0.57,p < 0.01)and fraction (23,24), rapid blood clearance (8,10,21) and the the abnormal coronary territories (k = 0.63, p < 0.0005).The lack of major redistribution (8,13,21 ). A possible approach agreementof nitrate-inducedperfusionchangeswith postrevas to overcome these limitations could be administering of cularizationfunctional outcome was excellenton a patient (k = 1, p < 0.0005), and coronary territory basis (k = 0.82, p < 99mTcsestamibi with a vasodilating stimulation to improve 0.0005). Conversely,the agreement between nitrate and pos tracer delivery to hypoperfused areas and, hence, its uptake trevasculanzationFPRNAwas poor: k = 0.18, ns. Conclusion: in viable tissue. Nitrate administration is known to increase These data suggest that the nitrate-inducedchanges in °@“Tccoronary blood flow (25—31) and 201Tl and 99mTc@ sestamibi perfusion imaging are useful to detect hibernating teboroxime uptake in hypoperfused territories (32—34). myocardium which recovers its function after revascularization. Furthermore, nitrate administration in combination with Key Words: first-passradionuclideangiocardiography;hiber functional imaging has predicted the postrevascularization nating myocardium; nitrates;technetium-99m-sestamibi outcome of asynergic territories (35,36). This study was undertaken to verify whether acute ad J NucI Med 1995;36:1994-2000 ministration of isosorbide dinitrate can improve 99mTc@ses@ tamibi uptake in hypoperfused territories and to evaluate the value of this phenomenon in predicting the postrevas cularization outcome of asynergic myocardium. We also ibernating myocardium recovers its function once performed first-pass radionuclide angiocardiography coronary blood flow has been restored (1,2). The current (FPRNA) during 99mTc@sestamibiinjection under baseline approach to detect hibernating myocardium is based on the conditions and with nitrates to compare the relative accu racy of perfusion and functional nitrate imaging in detect ReceivedAug.5, 1994;revisionacceptedMay15,1995. ing hibernating myocardium and to evaluate the effect of Forcorrespondenceor repnntscontact:RobertoSdagrà Nudear. MedK@inenitrate-induced wall motion changes on 99mTc@sestamibi Unit, Department of Clinic@Pathophysiology, University of florence, Viale Mor gagni85,50134Florence,Italy. activity in asynergic areas.

1994 The Journal of NuclearMedicine•Vol.36 •No. 11 •November1995 METHODS by modification of the global LVEF of 3 ejection fraction units compared with the baseline value. The choice of the threshold of Patients 3 ejectionfraction unitswasmadetakinginto accountthe FPRNA We studied 28 patients (24 men, 4 women; aged 42—71yr, mean reproducibility in our laboratory (37). For regional wall motion age 56.5 ±8.5 yr), who had been scheduled for a coronary revas analysis, the left ventricular wall was divided into five segments cularization procedure because of low-threshold effort angina. and the motion of each segment was evaluated using the following Further inclusion criteria were: history of previous myocardial scoring scheme: 0 = normokinesis, 1 = mild hypokinesis, 2 = infarction dating back at least 3 mo, recent coronary angiography severe hypokinesis, 3 = akinesis and 4 = dyskinesis (37). The results, presence of left ventricular dysfunction (ejection fraction anterior, antero-apical and apical segments were assigned to the <50%)andaregionalwallmotionabnormality.Exclusioncriteria territory of the left anterior descending artery and the inferior and were: history of unstable angina in the 3 mo immediately prior to infero-basal segments to that of the posterior descending artery. the study, presence of heart disease other than coronary artery For each study, an image set, including left ventricular end-dia disease or history of previous revascularization procedures. stolic and end-systolic outlines, representative cycle cine movie S@dy Pntocol display, regional ejection fraction images and Fourier amplitude All patients were studied after withdrawal of nitrate therapy for images, was prepared and submitted blindly and independently to at least 48 hr; all other therapies were continued. Before revascu two experienced observers. In case of disagreement, which was larization, patients underwent 99mTc@sestamibiimaging under registered in 25/420 (6%) assigned scores, the final score was given baseline conditions and with nitrate administration. The two stud by consensus with the help of a third observer. According to the ies were performed randomly, at least 24 hr apart, with the pa comparison between the nitrate or postrevascularization score and tients in stable clinical conditions. Each study included the collec the related baseline value, each asynergic segment was classified as tion of FPRNA during 99mTc@sestamibiinjection for perfusion either improved (wall motion score decrease 1 grade) or un scintigraphy. For the nitrate study, 10mg isosorbide dinitrate were changed. Similarly, a vascular territory was classified as improved diluted in 100 ml isotonic saline solution and infused over 20 mm, if it included at least one segment with a wall motion score while monitoring heart rate and blood pressure. Technetium-99m- decrease l grade. Improvement in the postrevascularization sestamibi was injected as soon as systolic blood pressure dropped study was also used to classify the territory as hibernating. >20 mmHg or systolicblood pressure was <90 mmHg. Otherwise, the tracer was administered after 15 mm of isosorbide dinitrate Technetium-99m-Sestamibi Scintigraphy infusion. Rest FPRNA and 99mTc@sestamibiperfusion SPECF SPECI' data were collected 60 mm after wmTc@sestamibiinjec were repeated at least 3 mo after coronary bypass grafting, or at tion on a gamma camera equipped with an ultra-high resolution least 1 mo after coronary angioplasty, to assess the evolution of collimator, with a 20% window centered on the 140-keV photo both global and regional left ventricular function and coronary peak of 99mTc The gamma camera head rotated in step-and-shoot perfusion. Informed consent to participate in the study was ob mode over a 180°arc, from the 45°right anterior oblique to the 45° tamed from all patients. The study protocol had been previously left posterior oblique view, with 60 projections of 20 sec each. approved by the ethics committee of our institution. Images were collected with a 1.4X zoom factor and stored on 64 X 64 matrices. Image reconstructionwas performed using back Coronary Angiography projection without a preprocessing filter and with a Wiener recon Cardiac catheterization, including selective coronary angiogra struction filter (dumping factor = 1, FWHM = 8 mm). No atten phy in multiple projections, was performed within 15 days before uation or scatter correction was used. The transaxial slices were or after the scintigraphic study. The main epicardial coronary realigned along the heart axis obtaining short-axis, vertical and arteries were evaluated by two observers, who were blinded to the horizontal long-axis slices. clinical and scintigraphic data. Each vessel was graded as having For quantitative evaluation of the tomographic images, the significant stenosis if the lesion restricted the lumen by 50%. short-axis slices from the first slice with apical activity to the last First-Pass Radionuclide Angiocardiography slice with activity at the base were used (38). Count profiles were FPRNA was acquired in the 300right anterior oblique projec generated by computer and plotted on a two-dimensional polar tion, with the patient supine, using a gamma camera equipped with map for comparison with a gender-specific data base of rest 99mTc@ a low-energy, all-purpose collimator. A 20% window was centered sestamibi studies performed on normal control subjects (39). The at the 140-keV photopeak of 99mTc.Twenty-five millicuries (925 lower limit of normal range was set at 2.5 s.d.s below the mean of MBq) 99mTcsestamibiwere injected into a saline-filledtubing the gender-specific control group (38,39). The extent of abnor extension ending with a three-way stop-cock and connected to an mally low uptake was first expressed as a percentage of the entire indwelling cannula, previously inserted into an antecubital vein of left ventricular wall. The quantitative polar map was then divided the right arm. The tracer bolus was then injected with forceful into three territories corresponding to distribution of the three pushing with a booster flush of 20 ml saline solution (37). The coronary arteries. For each vascular territory, a separate analysis bolus quality was controlled using the time-activity curve in a of tracer uptake was performed and the extent of the abnormality region of interest (RU!) drawn on the superior caval vein and was expressed as a percentage of the single territory. A defect had defined acceptable when the FWHM was <1 sec. The study was to be >12% of the left anterior descending and the circumflex acquired in frame mode (24 frames/sec) using a 2 X zoom factor territories and >8% of the right coronary artery territory for and EKG gating to reconstruct the representative cardiac cycle. clinical significance (40). The patient's total perfusion defect and Left ventricular ejection fraction (LVEF) was calculated twice significant regional defects in the nitrate and postrevascularization from the background-subtracted time-activity curve and the mean studies were compared with related baseline values. On the basis value was used for data analysis. The difference between the two of this comparison, each patient study and territory defect was measurements was never >2 ejection fraction units. A significant classified as either improved (extent decrease of >10% of the change in postrevascularization or in nitrate FPRNA was defined baseline value) or unchanged. For comparison with FPRNA data

NitrateTechnetium-99m-SestamibiImaging•Bisi et al. 1995 TABLE I TABLE 2 Patient Characteristics Hemodynamic Response to the Nitrate Test Patients 28 BaselineNitratepHeart PriorInfarctSites 32 120.05Systolicrate(bpm)66 ±1274 ± Anterior 15 15<0.0005DiastolicBP(mmHg)125 ±17105 ± Inferior 9 10<0.05MeanBP(mmHg)75 ±1068 ± AnteriorandInferior 4 10<0.0005BPBP(mmHg)92 ±1179 ± Coronary Angiography Three-vesselCAD 12 = artetialbioodpressure. Two-vesselCAD 5 One-vesselCAD 11 PreoperativeLVEF 36.2%±9.9% Thirty-one baseline asynergic segments had wall motion (range16%—49%) scone improvement, whereas 64 were unchanged. There fore, 19 FPRNA vascular territories (13 anterior and 6 CAD = coronaryarterydisease;LVEF= left ventricular ejection posterior) showed significant postrevascularization wall fraction. motion recovery and were classified as hibernating. In the remaining 25 asynergic vascular territories, the total wall on a vascular territory basis, only the left anterior descending and motion score remained unchanged. the right coronary artery defects were considered and compared In postrevasculanization perfusion SPECT, 13 patients with anterior and posterior FPRNA territories, respectively. had significant decreases in total extent of perfusion defects and 15 had an unchanged value. In terms of vascular tern S@cal Ana@ie Data are expressed,when appropriate, as the mean ±s.d. tories, 23 showed a perfusion defect decrease and 30 an Hemodynamic changes during the nitrate test were analyzed using unchanged defect extent. one-wayanalysisof varianceand the Bonferronicorrectedt-test. Hemodynamic Findings During Nitrate Infusion Agreement between the nitrate-induced and postrevasculanization Technetium-99m-sestamibi was injected after 15 mm changes was evaluated by chi square test with Yates correction and into 20 patients; in another eight, the injection was antici calculating the kappa value; values >0.75 represent excellent pated as required by previously mentioned blood pressure agreement, values between 0.40 and 0.75 show fair to good agree criteria. Table 2 shows the hemodynamic parameters at the ment and values <0.40 show poor agreement (41 ). Bonferroni correction was used for multiple comparisons. A probability value beginning of the infusion and at the moment of tracer of p < 0.05 was significant. injection. No patient suffered from adverse effects due to the nitrate infusion. RESULTS First-Pass Radionud@e Angiocardiography General Findings Figures 1 and 2 show two examples of baseline and Table 1 summarizes the main preoperative findings of all nitrate FPRNA images. Eleven patients had an ejection patients. According to baseline FPRNA, there were 95 fraction increase, whereas the remaining 17 had unchanged asynergic segments in 44 vascular territories (23 anterior, 21 ejection fractions. A low agreement (k = 0.24, ns) could be posterior). Thirty-two were the site of a previous infarction; demonstrated between nitrate-induced and postrevascular the remaining 12 included mostly asynergic segments con ization ejection fraction changes (Fig. 3). For segmental tiguous to the infarcted ones. Nonetheless, the 12 nonin analysis, 44 had wall motion scone improvement and 51 fancted asynergic areas were supplied by critically stenotic remained unchanged. Figure 3 shows the comparison be coronary arteries. tween these changes and those observed in postrevascular In the baseline perfusion study, 53 vascular territories (21 ization FPRNA. In this case, the agreement was quite poor, left anterior descending, 11 circumflex and 21 night cono but significant (k = 0.32, p < 0.01). For vascular territories, nary) showed a significant perfusion defect. All of them 30wereimprovedand14unchanged,withlowagreement were asynergic. Therefore, 2 asynengic vascular territories with the postrevasculanization data (k = 0.18, ns) (Fig. 4). had an apparently normal 99mTcsestamibi uptake. More Perfusion Imaging over, all normokinetic territories showed an apparently Two examples of baseline and nitrate myocardial scintig normal perfusion pattern. raphy are shown in Figures 1 and 2. A significant decrease Postrevascularization Findings in global extent of the perfusion defect was observed in 11 Complete revasculanization of all stenosed major epicar patients. The remaining 17 patients had unchanged global dial vessels was obtained using multiple bypass grafting in extent of perfusion defects. There was a fair agreement 18 patients and coronary angioplasty in 10.An increase 3 between nitrate-induced and postrevasculanization changes ejection fraction units in the LVEF was observed in 11 (k = 0.57, p < 0.01, Fig. 5). Furthermore, nitrate-induced patients. The remaining 17 patients showed either a change global perfusion defect changes correctly classified all pa <3 ejectionfractionunitsonanejectionfractiondecrease.tients as having significant ejection fraction increases or no

1996 The Journal of Nuclear Medicine •Vol. 36 •No. 11 •November 1995 @ .@ 3@

LVEFpost-rev.vs. baseline

0 11 @ .E FP-RHA

C Improved65 S______j11 @ Nt @ Improved 12 17 @ SPEC'!' ;@ -;; 28 Agreement = 64% Kappa ±SE(K) = .24 ±.19

FPRNA post-rev. vs. baseline REST ISON POST—REV 0 FIGURE1. FPRNAandperfusionpolarmap(SPECT)ofapatient with single-vessel CAD. Prerevascularization baseline images 2 FIGURE 3. Agreement for C I@ij global (top) and segmental (REST)showantero-apicalakinesiawitha perfusiondefect.The 0 Improved 22 22 44 nitrateimages(ISDN)showsignfficantwallmotionimprovementand C ______(bottom)functionalchangesbe perfusiondefect reduction.The postrevasculanzation(POST-REV) C Not tween postreva.scularization FPRNAconlirmsantero-apicalfunctionalrecovery. Improved4251 (post-rev) and nitrate FPRNA. a. Total 31 64 95 Both studies were compared U. with the prerevascu@hzation Agreement=67% baselinestudy. SE(K)= standard Kappa±SE(K) = .32 ±.10 significant increase (k = 1, p < 0.0005) (Fig. 6). Of the 53 error of kappa. vascular territories with significant perfusion defects on baseline scintigraphy, 23 had a significant decrease in the defect extent with nitrates and 30 remained unchanged; DISCUSSION there was good agreement with the postrevasculanization Nitrates and Coronaty Blood Flow changes (k = 0.63, p < 0.0005) (Fig. 5). When nitrate Organic nitrates are a mainstay of coronary artery dis induced perfusion changes in the 44 asynengic FPRNA ease therapy. Their anti-ischemic effect is mainly related to territories were compared with the classified territories decreases in myocandial oxygen consumption, which are according to postrevasculanization functional modifica obtained by lowering of preload and aftenload in the two tions, 18 of 19 hibernating territories were identified (16 by ventricles (42). Recently, several reports have suggested significant decreases in perfusion defect extent and 2 by that coronary vasodilation also plays an important role in completely normal perfusion in the baseline and nitrate anti-ischemic mechanisms of nitrates (28,42,43). Specifi studies). On the other hand, absence of hibernating myo cally, it has been hypothesized that nitrates dilate flow cardium was correctly predicted in 22/25 territories. Oven all, there was an excellent agreement between nitrate-in duced perfusion changes and presence or absence of postrevasculanization functional recovery (k = 0.82, p < FPRNApost-rev.vs. baseline 0 0.0005) (Fig. 4). C I C _____E E@ S Improved 15 153010 Not 4 @14 @ _Improved __ @ FP—RNA Total 19 25 44 Agreement=57% Kappa SE(K) = .18 ±.13

FPRNApost-rev.vs. baseline

SPECT S I

Improved18321Not REST ISON POST—REV FIGURE4. Agreement be tween presence or absence of FIGURE 2@ FPRNAandperfusionpolarmap(SPECT)ofa patient Improved2223 regional posfrevasctiarizatk@nre @ withthree-vesselCAD.Nitrateimagesdemonstrateremarkableand j__Total 19 25 44 coveryand nitrate-inducedfunc diffuseimprovementinwallmotionpattern,buttheperfusiondefect tional (top)and perfusion(bottom) does not appear modified. After revascularization,there is no func Agreement= 91% changes in comparable asynergic Kappa±SE(K) = .82 ±.15 tionalrecovery. tenftones

NitrateTechnetium-99m-SestamibiImaging•Bisiet al. 1997 @ :@

SPECT post-rev.vs. baselIne cell death (22). This is not unexpected, considering the S kinetics of @Tc-sestamibi(8,10—14,21—24).Thus, it is not C I I! a z@ @2 surprising that most data in humans suggest that rest @mTc@ 2 sestamibi uptake may underestimate myocardial viability C ___ E E Improved 9 2 11 compared with other imaging methods such as PET or 2O1@fl particularly if qualitative image analysis is used Not Improved413'17 (17,18,20). Moreover, functional recovery after revascular ization was found in segments which, according to quanti @ Total 11 17 28 tative analysis of rest @mTc@sestamibiuptake, had appar Agreement= 79% @ Kappa ±SE(K) .57 ±.19 ently necrotic tissue (19). The importance of reduced tracer delivery in producing low tracer uptake by viable, but hy SPECT post-rev. vs. baseline poperfused regions is supported by the demonstration that the collection of @mTc@sestamibiredistribution images re duces, at least partially, the underestimation of viability compared with 201'fl imaging (20). On the other hand, Improved 18523 territories with chronic hypoperfusion at nest may have FiGURE5@Agreement for Not coronary flow reserve that can be elicited by pharmacolog 5 25 30 global(top)andregional(bottom) Improved perfusion changes between pos ical stimulation (46). I trevascularizationand nitrateto Total 23 30 53 Nitrate Perfusion Imaging mography. Both StUdIeSwere Agreement= 81% compared with the prerevascu In our patient population, most asynergic vascular tern Kappa ±SE(K) = .63 ±.14 larizationbaselinestudy. tories had quantitative abnormal @Tc-sestamibi uptake. In only 2 of 44 asynergic territories did apparently normal tracer uptake suggest the presence of hibernating myocan limiting obstructions in coronary arteries (27,29). Further dium. With nitrate administration, some patients and vas more, there is the well-known vasodilating effect of nitrates cular territories had a clean decrease in global and regional on coronary collaterals (26), which also explains the im uptake defect extent, respectively, whereas in the majority provement in 201T1uptake after nitroglycerin infusion in of cases unchanged perfusion was demonstrated. A com hypoperfused regions related to totally occluded coronary panison of these two different responses with the postrevas arteries but with well-developed collateral circulation (31). culanization outcome confirms that nitrate @Tc-sestamibi More recently, the increase in coronary blood flow is con imaging is an effective method to detect viable hibernating sidered to be the cause of higher numbers of perfusion myocandium. Nitrate-induced modifications in defect cx defects classified as reversible by 201'flreinjection imaging tent agreed with the perfusion changes observed after re performed with nitrate administration (32,33). vasculanization. All patients with a positive response to the nitrate test had significant improvement in global and re Technetium-99m-Sestamibi and Myocardial Viability gional ventricular function after revasculanization. In the These data suggest that acute administration of nitrates vascular territories, 86% of those with improvement on could be helpful overcoming the limitations of @mTc@sesta@ nitrate imaging, demonstrated functional recovery after re mibi imaging of viable hibernating myocardium. There is vasculanization. Conversely, 96% of the territories in which clear experimental evidence that @Tc-sestamibiuptake the presence of hibernating myocardium had been excluded and retention require the integrity of cell membrane and did not improve after revasculanization. In brief, nitrate cellular viability (9,14) and that infarcted myocandium is @“@Tc-sestamibiperfusion imaging accurately classified the unable to extract tracer (12). Tracer uptake in areas of postrevasculanization outcome of all patients and 91% of reduced flow and partially impaired viability, however, the asynergic vascular territories. seems more directly influenced by blood flow rather than Nitrate Functional Imaging The possibility that long-lasting nitrate-induced wall mo LVEF post-rev. vs. baseline tion changes produce apparent activity increase in the col @ S .5 lected 99mTcsestamibi perfusion images through partial volume effects (45,47), however, had to be considered. Reduction in cardiac loading and, possibly, the increase in Improved11011Not collateral blood flow may explain the detection of contrac tile reserve in asynergic areas with acute nitrate adminis

Improved01717 tration (30,35,36). This finding has been correlated with a FIGURE 6. Agreement be positive postrevasculanization outcome (35,36). To evalu @ Total 11 17 28 tween presence or absence of postrevasculanzation LVEF im ate this possible interaction and to test the hypothesis that Agreement = 100% functional nitrate imaging could be as effective as perfusion Kappa±SE(K)= 1.0±.19 provement and nitrate-induced changesin globalperfusion. imaging to detect viable hibernating myocardium, we also

1998 The Journalof NuclearMedicine•Vol.36 •No. 11 •November1995 assessed acute functional changes induced by nitrate infu should have diminished the inherent problems of this com sion by acquiring FPRNA during 99mTc@sestamibiinjection. parison. Although the nitrate FPRNA results agreed with those of perfusion imaging in some patients and vascular territories, CONCLUSION there were also notable discrepancies. Specifically, a re This study demonstrates that acute nitrate infusion im markably higher rate of positive responses to nitrate infu proves the capability of rest @mTc@sestamibiperfusion im sion was observed both on a patient and vascular territory aging to detect viable hibernating myocandium, resulting in basis. When the nitrate FPRNA results were compared accurate prediction of postrevasculanization outcome of with the postrevasculanization outcome, however, most of both patients and vascular territories. In contrast, the acute these additional positive responses appeared to be false effects of nitrate infusion on ventricular function, as as positives because the patients and vascular territories in sessed by FPRNA, appear to be significantly less reliable, volved did not show any functional recovery. This finding particularly because of the nonspecific meaning of a posi could be explained as a nonspecific consequence of de tive response in terms of ventricular function. Further stud creases in cardiac pre- and afterload caused by peripheral ies comparing nitrate 99mTcsestamibi perfusion imaging hemodynamic actions of nitrates (42,43). On the other with other currently used methods are warranted to define hand, the rate of false-negative responses to nitrate infusion its clinical role in patients with chronic coronary artery was higher compared with perfusion imaging. Therefore, disease and left ventricular dysfunction. the value of nitrate functional imaging appeared signifi cantly lower than perfusion scintigraphy for patient and ACKNOWLEDGMENTS vascular territory classifications. The remarkable disagree ment between functional and perfusion modifications gives Presented in part at the 41st Annual Meeting of the Society of evidence against the hypothesis that increases in @Tc Nuclear Medicine, Orlando, FL, June 1994. activity are mainly caused by nitrate-induced effects on wall motion and thickening, which could still be present during REFERENCES tomogram acquisition. 1. BraunwaldE, RutherfordJD. Reversibleleft ventriculardysfunction:evi dence for the “hibernatingmyocardium.―I Am Coil Cardiol 1986;8:1467— 1470. Study Umitations 2. RahimtoolaSH.Thehibernatingmyocardium.AmHeartI 1988;117:211— These results must be evaluated with caution because of 221. 3. TillischJH, Brunken R, Marshall R, et al. 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2000 The Journal of Nuclear Medicine •Vol. 36 •No. 11 •November 1995