Improved Detection of Viable Myocardium with Thallium-201

Improved Detection of Viable Myocardium with Thallium-201 Reinjection in Chronic Coronary Artery Disease: Comparison with Technetium-99m-MIBI Imaging Simone Maurea, Alberto Cuocolo, Emanuele Nicolai and Marco Salvatore Departmeni@cofNuclear Medicine, Unive,@y Fede@icoII, and National Cancer IMtitute, Napol4 fta@y

Exercise-redistribution@°ii withreinjectionat rest and exercise rest @Tc-methoxy isobutylIsonitrile(MIBI)cardiacimagingwas performed in a patient wWimultivesselchronic coronary artery disease (CAD)and evaluated before and after coronary raves cuIa@[email protected] reinjection showed reverssble defects of

the infodorandseptalwallsandirreveraible defectof the Infero a@ region.Technetlum-99m-MIBI scantigraphydemonstrated irreversibledefects of the infedOr,septal and infero-apicalre gions. Aftercoronaryartery bypass grafts, both thalliumreinjec tion and @‘1c-MlBl images showed onlyirreversibledefects of the infero-apicalregion.Func@onal recoveryof the inferiorand septal walls was observed on two-dimensionalechocardiogra phy. Thalliumreinjectionidentftiesseveraly ischemic but viable myocardiummore accurately than @Tc-MlBl in chronicCAD. Thalliummyocardlalimagingv@threinjectionat rest is recom mended for evaluating patients with chronic ischemic leftvan tricular dysfunction to determine ifthese patients are candidates

for revascularizationprocedures. KeyWords: chroniccoronaryarterydisease; thallium-201;tech nelium-99m-MIBI J NuclMed1994;35:621—624

tion regardingviable myocardium to those offered by cx ercise-rest S@@Tc.MJBIcardiac imaging (11,12). The improved detection of viable myocardium with thallium reinjection compared to @‘@‘Fc-MIBI in a patient with chronic CAD evaluated before and after coronary revas cularizationis reported. CASE PRESENTAtiON A 54-yr-old man with CAD was initially evaluated in our de

partmentin July1990.Thepatienthada clinicalhistoryof previ ous myocardialinfarction(May1988)of thepostero-inferior wall ofthe leftventricleandwastreatedwithnitrates,calciumchannel blockingagents and plateletaggregationinhibitors.On admission, the patientwas asymptomatic,andphysical examinationrevealed a resting heart rate of 79 bpm and blood pressure of 115/80.

BaselineECG showedregularsinus rhythm; 0-waves with asso ciated ST-segment and T-wave abnormalities were present in leads D2, D3 and aVF. Bicycle ECG stress test demonstrated

ST-segmentdepression (>2 mm) in leads V4 and V5, without angina or other symptoms. Echocardiography

revealed resting left

ventricular ejection fraction (LVEF) of 40%. AnalysiS of regional LV function on echocardiographicimages demonstrated septal,

inferiorand micro-apicalakinesia.Coronaiyangiographyshowed three-vessel CAD with a 90% stenosis ofthe left anterior descend

xercise-redistribution @°@Tl myocardial scintigraphy with reinjection at rest has been shown to accurately dii ferentiate irreversibly fibrotic myocardium from severely hypoperfused but still viable tissue in patients with coro nary artery disease (CAD) (1—4).Technetiuin-99m-meth oxy isobutyl isonitrile (MIBI) and thallium imaging have shown excellent agreement in the detection of CAD (5), but the precise role of @Tc-MIBI in the evaluation of myocardial viability in patients with chronic ischemic LV dysfunction is still under investigation (6—10).Previous studies suggested thatexercise-redistributionthalliumscin tigraphywith reinjectionat rest provides superiorinforma

ing arteiy and a 75%stenosis of the rightcoronaiy vessel and of the obtuse marginalbranchof the circumflexcoronary artery. On the basis of clinical histoiy and cardiacwork-up, the diagnosis of

ischemicchronicLV dysfunctionwas made.Therefore,radionu clide imagingstudies were performedto assess myocardialperfu

sion andviabilityin orderto determinethe need for coronary revascularizationprocedures.Antianginaltherapywaswithdrawn 3 days before imaging. Exercise-redistribution @°“fl scintigraphywith reinjection at rest was performedas previously described (11). Five days later,

exercise-rest @Tc-MIBI imagingwas also performed using a two-dayprotocolas previouslydescribed(11). Hemodynamic parametersrecordedundercontrol conditions and duringthe two

exercisetestsdidnotshowsignificantdifferences. Thallium and tffC 1. Each

ReceivedMay26, 1993;revIsionaccepted Nov.11, 1993. Forcorrespondenceor reprintscont@t AlbertoCuocolo,MD,ViaPos@hpo 66, 80123Napoh,ftaly.

Detectionof Myocardial“Hibernation― • Maurea at ai.

view

@“Tc-MIBI imaging results are illustrated in Fig was

normalized

to its own

maximum.

The

exercise-redistributionthalliumstudy showed irreversibleperfu sion defects of the inferior and micro-apical regions and of the

distalsegmentofthe interventricularseptum.Thalliumreinjection

621

A

THALLIUM-201

fects of the inferiorand mIcro-apicalmyocardialregions. A mod erate irreversibledefect was also present in the distal segment of 0

Anterior

@

LAO 45

Exercise

‘

the

interventricular

septum.

On the basis of thalliumreinjectionresults, the presence of severelyischemicbut stillviablemyocardiumin the inferiorwall andin the distalsegmentof the interventricular septumwas de tected. Therefore,the patientwas a potentialcandidatefor coro nary revascularization.On October 1990,coronaryartery bypass graft(CABG)was undertaken, with grafts placed from the aorta to

_____________ _____________

the left anteriordescendingarteryandto the rightcoronaryyes sel. Thepostoperativecoursewas unremarkable. One year later (November 1991), the patient was re-admitted to

@

Redistribution

%

/

our departmentfor postsurgicalevaluation.The patientwas on treatmentwith plateletaggregationinhibitorsonly. Postoperative echocardiography showedanLVEFof 55%.Analysisof regional LV function demonstrated improved wall motion at rest of the

septalandinferiorwallcomparedto thepreoperativestudy.Post operative201T1and @°‘Tc-MIBI imagingstudieswere also per formed followingthe same acquisitionand processingprotocols @

Reinjection

11%

esv@ _____________

B

Tc-99m

MIBI

Anterior

LAO 45°

used for the preoperative evaluation. Postoperative thallium and @Tc-MIBIimaging results are il

lustrated in Figure 2. Exercise-redistributionthallium imaging with reinjectionat rest showedan irreversibledefectof the in fero-apicalregion. Exercise thalliumuptake in the inferiorwall andin thedistalsegmentof the interventricular septumwas nor mal. Exercise-rest @Fc-MffiI imagesshowed an irreversible defect of the infero-apicalmyocardialregion.Exercise @Tc Mifil uptake in the inferiorwall and in the distal segmentof the interventricular septum was normal. The patient was then dis charged from our department

and his clinical follow-up was un

remarkable. Exercise DISCUSSION

Rest

The case illustrated here is a clear starting point for discussing the controversies regarding the comparison be tween thalliumand @Tc-MIBI imagingfor identifyingvi able myocardium in patients with chronic ischemic LV dysfunction (13). In the pre-CABG evaluation of this pa tient,

@

inferior,

apical

and septal

akinesia

were

detected

on

the echocardiography study, and LVEF at rest was 40%. FiGURE1. (A)Preoperative exerclse-redlstdbutlon@11 Both standard exercise-redistribution thaffium and exer imaging with reinjectionat rest Exercise and redistributionanterior cisc-rest @°@Tc-MIBI imaging showed irreversible defects views demonstrate an irreversible perfusion defect invoMng the of the inferior and infero-apical myocardial walls and of the inferiorregion.Thalliumreinjectionshowsenhancedtraceruptakein distal segment of the interventricular septum, suggesting the inferiorregion.Exerciseand redistribution leftanterioroblique (LAO)450viewsdemonstrateIrreversibleperfusiondefectsinvoMng the presence of necrotic myocardium. However, thaffium the Infero-apicalregion and the distal segment ofthe interventricular septum. Thallium rsinjectlon shows enhanced tracer uptake in the

reinjection at rest showed enhanced tracer uptake in the

inferior wall and in the septum, suggesting the presence of change in tracer uptake in the infero-apicalregion. (B) Preoperative severely ischemic but still viable myocardium in these re [email protected] restanterior gions and therefore the possibility of obtaining functional views demonstrate an irreversible perfusion defect invoMng the recovery of these myocardial segments after revasculariza Inferior region. Exercise and rest left anterior obique (LAO)45° tion. Conversely, reinjection images showed no change in views demonstrate an irreversible perfusion defect lnvoMng the thaffium uptake in the micro-apical region, suggesting the infero-apicalregionand a moderateirreversibleperfusiondefectin distal segment of the interventñcular se@um and no signdlcant

the distal segment of the interventilcularseptum.

presence

of irreversibly

scarred tissue in this area.

no significantchangein thalliumuptakeafterreinjection.Exer

Preoperative thaffium reinjection findings were con firmed by functional evaluation after CABG. Postoperative echocardiography showed improvement of global and re gional LV function, with an ejection fraction of 55% and improved wall motion of the inferior and septal regions.

cise-rest @°@Tc-MIBI scintigraphyshowed severe irreversiblede

Furthermore, inferior and septal myocardial segments had

622

The Journalof NudearMedicine• Vol.35 • No. 4 • April1994

at rest demonstratedenhanced tracer uptake in the inferior and septalwalls. The defect located in the infero-apicalregionshowed

normal uptake on both postoperative exercise thallium and @Tc-MIBIimages, while the micro-apical region still

accurately predicted functional recovery after revascular ization.

showed an irreversibledefect. Therefore, the preoperative In this report, the discordant results between preopera thallium study with reinjection at rest correctly identified tive thalliumand @Tc-MIBI imagingmay be explained by the presence of viable tissue in regions where @Tc-MIBI the differentkinetic featuresofthese two tracers. Thallium images showed irreversible perfusion defects, and, thus, 201 is a potassium analog which has been developed as a myocardial perfusion tracer reflecting initial tissue uptake in proportion to coronary blood flow delivery (14). How

A

ever, thallium is also a marker of myocardial viability be

THALLrnM-201 Anterior

cause only viable cells with an intact membrane retain the tracer, reflecting cell membrane integrity (15). Therefore, LAO 45°

severely ischemic but still viable myocardium preserves

____________

the capability to take up thallium even though coronary blood flow is extremely reduced. When scarred myocar

@

p d@@rr dium ispresent, thallium isnot taken upasinnormal orin

Exercise

.@:

_____________

severely

hypoperfused

but

still

viable

tissue,

nary flow reserve modified by flow-dependent irreversibility

Reinjection

Tc-99m MIBI Anterior

LAO 45°

reflecting a region of decreased

coronary

@Tc-MIBI in isolated rat hearts

(8) and in the occiusion-reperfusion swine model of acute ischemia in vivo (9) are significantly reduced in necrotic myocardium. Technetium-99m-MIBI uptake in myocardial _____________

cells is diffusional and is not dependent on a sodium-po tassium-adenosine

Rest

extraction.

flow reserve or an area of reduced flow reserve around an infarction, respectively. Enhanced thallium uptake after reinjection within apparently irreversible thallium defects on redistributionimages has been shown to be compatible with the presence of severely hypoperfused but still viable myocardiwn (1—4).Therefore, although exercise-redistri bution thallium images do not reliably predict myocardial viability, thallium reinjection realizes a resting image su perimposed on stress images containing viability informa tion. Technetium-99m-MIBI is a cationic lipophiic myocar dial tracer which accumulates linearly in the myocardium according to coronary blood flow as measured by micro spheres (16). Recent animalstudies demonstratedthat the uptake and retention of

Exercise

@

of

Redistribution thallium images demonstrate reversibility or

Redistribution

B

because

very low coronary blood flow levels and myocardial cell death. Exercise thalliumimages reflect the distributionof increased myocardial perfusion during exercise or coro

‘4'

L@j

triphosphatase

pump. Previous

studies

demonstrated that this tracer is sequestered in the cyto

plasm and mitochondriain response to electrical potentials across the membrane bilayers (8, 17, 18). In particular, neg

____________ @

FiGURE 2. (A) Postoperative exercise-redistribution @@111

diac imagingwith reinjectionat rest. Exercise,redistributionand reinjectionanteriorviewsdemonstratenormalthalliumuptakeinthe inferiorregion.Exercise,redistributionand reinjectionleftanterior oblique(LAO)45° viewsdemonstratenormalthalliumuptakeinthe distal segment of the interventricular septum and an Irreversible perfusiondefect invoMngthe infero-apicalregion.(B)Postoperative

exercise-rest @“Tc-MlBl cardiacimaging.Exerciseand restanterior

ative mitochondrialand plasma membranepotentials seem to promote @Tc-MIBI uptake, and this mechanism may provide a model to better know the biodistribution of @“@Tc-MIBI in the heart muscle. Of note, cardiac tissue shows negative plasma membrane potentials and is rich in mitochondrial content. Therefore, changes in myocardial metabolism which modify membrane potentials could in fluence @Tc-MIBItissue uptake as demonstrated by Piwnica-Worms et al. (19). These authors showed that

views demonstratenormal @“Tc-MlBl uptakeinthe inferiorregion. Exerciseand rest leftanterioroblique(LAO)45° views demonstrate @°@Tc-MIBI net uptake into cultured heart cells ap normal°°@Tc-MlBl uptakein the distalsegment of the interventiic ularseptumand an irreversibleperfusiondefect invoMngthe infero proached a plateau level, implying that an equilibriumor apical region. steady-state process is involved in net cellular accumula

Detection of Myocardial“Hibernation― • Maurea at al.

623

tion of the tracer. Their results indicated that myocardial cell net accumulation and uptake kinetics can be affected by pharmacologicalalterationsin membranetransportand metabolic status, respectively (19). These data suggest that @Tc-MIBI has properties as a definitely good perfusion agent and a reasonably good viability tracer. However, the precise role of

@Tc-MIBIfor assessing viable myocar

diumin chronic CAD has not yet been completely clarified, and further experimental and clinical investigations are required (6,9,13). Moreover,

the apparently discordant

results of this case

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and PET imaging with “F-fluorodeoxyglucose.CimuLation 1991;83:26-37. and those of other studies in animal models (8,20—22) can 5. KahnMc McGhieI, AkersMS.etal.Quantitative rotational tomography be explained by examining the different mechanisms in with @‘11 and @c-2-methoxy-isthutyl-iaonitrile: a direct comparison in CAD by which regional LV function may be impaired in normal individuals and patients with coronary artery disease. Cuvulation 1989;7@1289-1293. the absence of irreversible myocardial damage. Two dii Machac3.Technetium.99m isonitrile:a perfusionor aviabilityagent?JAm ferent states, stunned and hibernated myocardium, may 6. CoilCardiol 1989;14:1685—1688. determine the presence of dysfunctional but still viable 7. Rocco TP, Dilsizian V. Strauss HW, Boucher CA. Technetium-99m isoni trile myocardialuptake at rest. II. Relationto clinicalmarkersof potential myocardium (23,24). In both of these situations, LV dys viability.JAm CoilCardiol1989;14:1678-1684. function is a potentially reversible process. Recent studies 8. BeanlandsRSB, DawoodF, WenW.H, et al. Are the kineticsof techne (8,21) suggested thatviablebut stunnedmyocardiummay tium-99mmethoxyisobutylisonitrileaffectedby cellmetabolismand viabil take up @Tc-MIBI similarly to the retention of thaffium. ity? Circulation 1990;82:1802-1814. 9. Liu PP.Technetium-99m-sestamibi: anotherwindowon myocardialviabil However, in chronic hypoperfused hibernating myocar 1991;32:298-299. dium, there are some limitations in the use of @Tc-MIBI 10. ity?JNucIMed MarzulloP, Sambuceti0, Parodi0. Theroleof sestamibiscintigraphyin to accurately identify viable tissue (11,12). Therefore, the radiolsotopicassessmentof myocardialviability.I NuciMed 1992;33:

@Tc-MIBIseems to be promising as a viability index in

the setting of stunned myocardiumafter reperfusion, but it could be inaccurate in the detection of hibernationwhen prolonged and sustained reduction of myocardial blood flow occurs. The patientreportedin this study had chronic CAD with LV dysfunction. Thus, the identification of hibernating

@

1925-1930.

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identifies

myocardiwn, while

severely

ischemic

but viable

@Tc-MIBIseems to be primarily a

perfusion agent and not an accurate marker of myocardial

viability in patientswith chronic CAD and LV dysfunction. When myocardial viability is in question, we recommend thallium cardiac imaging with rest reinjection for potential revascularization candidates with chronic ischemic left ventricular dysfunction.

624

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The Journalof NudearMedicine• Vol.35 • No. 4 • Apnl1994