Acute Subendocardial Myocardial Infarctionin Patients

Its Detection by Technetium 99-m Stannous PyrophosphateMyocardial Scintigrams

By JAMES T. WILLERSON, M. D., ROBERT W. PARKEY, M. D., FREDERICK J. BONTE, M.D.,STEVEN L. MEYER, M.D., AND ERNEST M. STOKELY, PH.D.

SUMMARYEighty-eight patients admitted to a coronary care unit with chest pain of varying etiology but without

ECG evidence of an acute transmural myocardial infarction had myocardial scintigrams using technetium-99m stannous pyrophosphate (99`Tc-PYP). Seventeen of these patients had ECG and enzymatic evidencesuggestive of acute subendocardial myocardial infarction. In each of these the scintigrams were positivedemonstrating increased `mTc-PYP uptake either in a faintly but diffusely positive pattern or in a well-localized strongly positive one. The remaining 71 patients did not evolve ECG or enzymatic evidence ofacute myocardial infarction. In each of these patients the myocardial scintigram was negative. Thus S9mTc-PYP myocardial scintigrams are capable of identifying the presence of acute subendocardial myocardial in-farction in patients. The absolute frequency with which subendocardial myocardial infarction can berecognized utilizing this technique will have to be established in a larger number of patients in the future.

Additional Indexing Words:Myocardial infarction Myocardial scintigrams Subendocardial infarction

ON STRICTLY CLINICAL GROUNDS it isdifficult to make a positive identification of

acute subendocardial myocardial infarction inpatients. The diagnosis from the electrocardiographicpoint of view depends on the presence of deep ST-segment depression and inverted T waves, but theseECG abnormalities, even when present, are notnecessarily specific for subendocardial infarction. Theonly evolution of this abnormal pattern is for thedepressed ST-segment to return to baseline and the Twaves to become upright over a period of days toweeks after infarction. Cardiac enzymes are dependedupon to substantiate the diagnosis of subendocardial

From the Departments of Medicine (Cardiac Unit) andRadiology (Nuclear Medicine) at the University of Texas(Southwestern) Medical School and Parkland Memorial Hospital,Dallas, Texas.

Dr. Parkey is a scholar in Radiological Research, James PickerFoundation. Dr. Meyer is an NIH postdoctoral research fellow sup-ported by HL05812; and Dr. Willerson is an EstablishedInvestigator of the American Heart Association.

Supported in part by NIH grants HL13625, N30010, HL15522,HL06292, the Southwestern Medical Foundation, and Harry S.Moss Heart Fund.

Address for reprints: Dr. J. T. Willerson, Department of InternalMedicine, Southwestern Medicai School at Dallas, The Universityof Texas, 5323 Harry Hines, Dallas, Texas 75235.

Received September 5, 1974; accepted November 18, 1974.

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infarction but even when elevated their elevation doesnot necessarily reflect cardiac damage. Since the sub-endocardial portion of the heart is the area mostvulnerable to myocardial ischemia in experimentalaniimals,"' 2 it seems possible that subendocardial in-farction might be a relatively common type of infarc-tion in patients. However, because of the difficulty inrecognizing subendocardial infarctions clinically it isprobable that some patients with subendocardial in-farction have gone undetected in the past and otherswithout infarction have been falsely identified as hav-ing had one.Thus the development of diagnostic methods

capable of identifying the presence of subendocardialinfarction with greater certainty than is presentlypossible would be of additional clinical help. Accord-ingly we have utilized technetium-99m stannouspyrophosphate (99mTc-PYP) to obtain myocardial scin-tigrams in 88 patients admitted to the coronary careunit* with chest pain of varying etiology in whom theinitial electrocardiograms did not reveal evidence ofacute transmural myocardial infarction. The purposeof this study was to identify the value of "mTc-PYPmyocardial scintigrams in recognizing the presence ofacute subendocardial infarction in patients.

*Parkland Memorial Hospital, Dallas, Texas.

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SUBENDOCARDIAL AMI BY SCINTIGRAM

Materials and Methods

Each of these 88 patients was admitted to the coronarvcare uinit at Parkland M1emorial lHospital with chest painsuggestive of the possibility of myocardial infarction.The patients were studied at their bedside in the coronary

care uinit utilizing a portable Nuclear Data scintillationcamera within the first few davs after admission. Somepatients also had myvocardial scintigrams performed in thenuclear medicine department using a Searle RadiographiesInc. Pho/Gamma HP scintillation camera with a 16,000 hlole"Chigh resolution' collimator. This scintillation camera is in-terfacecl to a PI)P-8 I computer with 12 K of core. Imagesare placed on 7 track magnetic tape for later retrieval. Thecomputer processinig utilizes image enhancernent to help toprecisely define the lesion. Each patient was imaged in theanterior, lateral, and oxne or more left aniterior obliqlue pro-jections 45 minutes to one hour after the intravenious inijec-tion of 15 mCi of 99mTc tagged to 5 mg of stannouspx rophosphate (1'Y1< wk-ithl coiitiniuiouis ECO; monitoring.Inforimed consent wxas obtained from ('each patient. Ne'ith'rarrhythmia rnor ob)vious side e>ffects were observed fromeither the injectiorn of the radiontuclide or from the imagingprocess itself. 'he irnagiing time for 3-5 views was ap-

proxirmatelv 15 miniutes.TFhe initial mvocarclial images were obtairned 1-3 days

after the onset of chest pain suggesting possible myoecardialirnfaretion. The scintigrams were graded from zero to 4+dependinig orn the activitv over the myocardium 1)b one ofthe aLthors (R. P ) without prior knowledge of the clinicalconidition of the patient. Zero represented no activitv and arnegative mvxoctrdial scintigram; 1+ was considered to bequestionable activitv; 2+ represented definite but faint ac-tivity and a positive mnvocardial sciintigram; 3+ and 4+represented dce finite and iniereased activitv within themyocardial scintigram.3 In this studv as well as in previotusOn1es,3 we have regarded 2-4+ mvocardial scinitigraphic up-take as represenitinig a positive mvocardial scintigram. Inthose seintigramns that w ere positive, the area of increaseduiptake "sas also described as leing anterior, inferior, lateral,or1 tru'e posterior.'

Results

Seventeen patients with electrocardiograms sug-gestive of subendocardial ischemia or infarction had99mTc-PYP myocardial scintigrams obtained (table 1).The mean age of these patients was 64.3 ± 3.26 (SF)years; nine were males and the remainder females.The initial scintigrams were obtained 64 + 4.34 hoursafter the onset of chest pain suggesting the possibilityof myocardial infarction. Each of these patients hadprominent ST depression and or prominent T wave in-version electrocardiographically consistent with sub-endocardial ischemia or infarction (fig. 1). The onlyECG evolution in these 17 patients was a return tobaseline of the deep ST depression over a period ofseveral days. Cardiac enzymes were elevated in all ofthese patients (either serum glutamic oxaloacetic trans-aminase or creatine phosphokinase or both) and sub-sequently evolved in the expected manner for acute

*\11'40 18 (stainious is-o)IisI)Iidte ) \lalliikt mit ( iiciniealW orks St. Iouis \lo.

Circualaon, Volumiie 51, March 1975

myocardial infarction. In these patients there was notanother obvious reason for the enzyme elevation otherthan myocardial infarction. The myocardial scin-tigrams were positive in each of these 17 patients withsubendocardial infarction (figs. 2, 3, and 4) (table 1).The patterns of radionuclide activity varied from afaintly but diffusely positive uptake in 11 patients(figs. 2 and 3) to prominent and apparently morelocalized uptake in six patients (fig. 4). In the sixpatients with subendocardial infarction with welllocalized 99mTc-PYP myocardial uptake the correlationbetween ECG and scintigraphic localization is shownin table 2. Serial follow-up myocardial scintigramsdemonstrated a decrease in the myocardial uptake of99mTc-PYP in six patients (second scintigram obtained369 ± 173.1 hours after initial one) and unchangeduptake in four (second scintigram obtained203 + 45.5 hours after initial one). The remainingseven patients did not have repeat myocardial scin-tigrams obtained, None of these patients died so thathistological data are rot available.The remaining 71 patients did not subsequently

evolve electrocardiographic or enzymatic evidenceof myocardial infarction. Their mean age was54.6 ± 1.89 years; 44 were males and the remainderfemales. The mean time of myocardial imaging inthese patients was 75.4 + 4.09 hours after the onset ofchest pain resulting in their hospital admission. Thedischarge diagnoses in these patients were angina pec-toris 54 patients; pericarditis, four patients; primarymvocardial disease, one patient; cardiac arrest of un-known etiology, two patients; aortic stenosis, one;mitral regurgitation, one; hypertension, two patients;congestive heart failure, one patient; cerebrovascularaccident, one patient; polyarteritis nodosa, one

'/ '1

AVL

AVF

.a

I.vii V4i

2i; /' ,.

Figure 1

X reoprsentaltiue examiple of the electrocardiogramzs obtained fr'ompatients withit chest pain and E(CC changes siigg s'tice of sitlen-docardial i.sclieiiia or infarction. ihe deep ST depsression ocver thelateral precordial leads is appaarent iti the fignire.

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WILLERSON ET AL.

Table 1

Patients with Acute Subendocardial Myocardial Infarction

1100 Iocalizationof infarction

Subenducardia.l

Suiibeii docardialStubenducardialStbendoca dia

ibeSubEetiducarldial

Subenducardial

SubeuidocardialSuibendocardial

SutbeidoeardRdiaSulbeuldou ardial

S ulbeuldo (iai

XSubeuldueatrdial

Time inmocardial scintigrarnperformed after infaretion (lhr)

4848

9648

72724,148

72

96

487248

7272

4848

Mtyocardlia] seintigrarn

:3+ high lateral2+ diffuitse

3+ p)osfteior2+ diffuise4+ i ufeirlda.t era1l2-+fanterior diffuse2+ (iffui ise3 pusS leru

2+ inferulatecal, diffuse2+ diffutse3+ atuiterir2+ (diffulSe2+ diffues2+ diffulse

3+ p)osflC'ii102+ (difTfuse2+ (dif'fukse

ANIT

Figure 2The top) panel demonst rates a myocardial scin tigramn obtained in an anteropostenrio r projection (A T)froni? a patient with

a suhen docardial ifarction. Note the diffu.se andi relatively faint tuptake of 9m Tc- Pi'P in the vscin tigrrar the hbot toni panI eldemionr.strates a niegative niyocardial scintigra nm obtained from a patient without niyocardial infarct ion for comparison7i.

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Patient

1L.1).1>8.K.L.A.l).W.W,

R1.M.11.74.

L.w.J.N.M.'.Cc;..V.I).

1)1).

Age/sex

63 FT44/M763 NIlXt} /Ml60/M4I5)2 74A.6:3 74l52/F44 /F82/F8ff/M91 IF66/F76/F59 7/50/F

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SUBENDOCARDIAL AMI BY SCINTIGRAM

ANT LAO LATFigure 3

XAnother example of the typical myocardial scintigraphic appearance of acuite subendocardial myocardial infarction in

patients. The pattern is that of a diffusely positive uptake of .99Tc-PYPI The three different panrels demonstrate theanterior (ANT), the left anterior obliquie (LAO), and the lateral (LAT) views.

patient; Parkinson's disease, one patient; syncopeetiology unknown, one patient; and chest walltrauma, one patient. In each of these patients themyocardial scintigram was negative.

DiscussionThe data obtained in these patients demonstrate

that acute subendocardial infarction can be recog-nized in at least some patients utilizing 99mTc-PYPmyocardial scintigrams. In the patients in this studythat had ECGs suggestive of subendocardial myocar-dial infarction and subsequent evolution of at leastone of the cardiac enzymes, the myocardial scin-tigrams were positive. The pattern of uptake of99mTc-PYP in the heart varied from being diffuselyand faintly positive to being well localized andstrongly positive. Just as is the case for 99mTc-PYPmyocardial scintigrams in patients with acutetransmural myocardial infarction, there is a tendencyfor the scintigram to become less positive or negativeseven or more days after infarction.3 It has not beenpossible to accurately localize the area of myocardial

Table 2ECG and Myocardial Scintigram Location of Subendo-cardial Infarction in Those Patients wvith LocalizediSiI~lTc-PYP UJptake

Mo(rardiial scintigramPatient. EC(X localization localizat ion

L.I ). LerJa,i l l Laerll

K.L. Septo lateral PosteliorW.W. Inllfr(iora ltet l Inferrior an latera.l1CM. Lat1era otroC.(11. Lateral PocsterioC. I At ero-wltel Anlt erior

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damage in most patients with subendocardial infarc-tion from the positive myocardial scintigram; this is incontrast to the ability to localize fairly precisely thearea of damage in transmural myocardial infarctions.3The reason for positive myocardial scintigrams in

patients with acute subendocardial infaretions as wellas in those with acute transmural myocardial infarc-tions is presumably due to the incorporation of thepyrophosphate into hydroxyapatite which is itselfdeposited near the region of mitochrondria in irrever-sibly damaged cells after myocardial injury.46However this hypothesis remains to be proven andmore importantly we are not yet certain that someischemic but not necessarily irreversibly damagedcells do not label with 99mTc-PYP. 99mTc-PYP andother phosphates have been used as bone-scanningagents for several years.7' Earlier investigations con-ducted in our laboratory demonstrated that `9mTc-PYPmyocardial scintigrams are positive in dogs with ex-perimental myocardial infarction; in experimentalanimals the myocardial scintigrams become positiveapproximately 12-14 hours after infarction andbecome less positive or negative 7-14 days later.9Earlier studies have also suggested that the 99mTc-PYPmyocardial scintigram may be negative in patientswith acute transmural myocardial infarction if onewaits more than six days after infarction to performthe test.3 False positive scintigrams might occur inbreast tumors, healing rib fractures, and or possibly insome patients with myocardial necrosis not based oncoronary artery disease, but the frequency with whichany of these are mistaken for myocardial infarction ispresently uncertain.

Other agents have been used in the past for myocar-dial imaging10-13 and at least one, technetium-99m

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WILLERSON FT AL.

ANT LAO LT

Figure 4

Th1c Ila) panici dc iii oiisIlstea iiiocardia/l .sciiligiaiii obtaii d vii /1ic fourthlldai froii ciapa tici /i aciz tIch .msiu/iei(c'c(l(diailillaicltiula i1l it lhic Ii /c incurecasccl uptlakc o " c(l 1' s Ouafliiten'iIM liatt/iiiii i,ii otccurs i1itI/i iube/ndiiocardialiijarc tiai.fI/l boltomi pain /cl csl itnsrals a ilyocaircdial inligiira frmaic paltienil wit/i anarcction.subcnac nitm iiijarc ioi in wh/iich/ tl/tiarea oj upcti1'ilakc is miorc l/ocalized I/ia occurrcd in iiiost of tI/ic patintis in I/h.s csciis

tetracycline, has been utilized to perform myocardialscintigrams in a few patients with nontransmuralmyocardial infarction.'0 The 99mTc-PYP appears tohave certain advantages over other imaging agentsthat have been studied however, in that it becomespositive relatively early after infarction, is inexpein-sive, safe, does not label the liver (making identifica-tion of diaphragmatic or inferior myocardial infare-tions relatively easy), and it is given intravenously.Technetium-99m tetracycline has the advantage thatit may also be given intravenously but the disadvan-tage of not becoming positive until 24 hours after in-farction and an additional 24 hours after the injectionof 99mTc tetracycline is necessary for optimal imagingconcentration in the infarct.'0

In summary, the data obtained in this study suggestthat `9mTc-PYP myocardial scintigrams identify thepresence of acute subendocardial myocardial infarc-tion in patients. Thus this myocardial imaging

procedure should be of diagnostic help in identifyingwhether ST-segment depression on the ECG impliessubendocardial infarction in patients admitted to thehospital with chest pain of varying etiology. However,the exact frequency with which 99mTc-PYP myocardialscintigrams are positive in patients with subendocar-dial infarction and how often the scintigrams arepositive in patients with histological evidence of sub-endocardial infarction but equivocal cardiac enzymechanges and electrocardiograms will have to be deter-mined in a larger number of patients in the future.

Acknowledgments

The aukthtors appreciate the hell) of the nurses, mendical hiotuseifficers, and technicians in the coironary care uirnit and nuclearne(licine dcepartment at Parkland \lernorial Hlospital il l)allas,Tl'exas ini the performiance of this studclsv We are especially gratefulto 1 r Ncirrnla n nce, ('huck G.rahama antd SaltisL is fur techniiicalassistance, and to N1 rs Betiuda Larn)ert for tvping the mlaulluscript.

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differences in ventricular tissue substrate levels due to cor-onary constriction. Am J Physiol 222: 705, 1972

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9. BONTE FJ, PARKEY RW, GRAHAM KD, MOORE J, STOKELY EM: Anew method for radionuclide imaging of myocardial infarcts.Radiology 110: 473, 1974

10. HOLMAN BL, LESCH M, ZWEIMAN FG, TEN1TE J, LowN, B,GORLIN R: Detection and sizing of acute myocardial infarctswith 99mTc (SN) Tetracycline. N Engl J Med 291: 159, 1974

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J T Willerson, R W Parkey, F J Bonte, S L Meyer and E M Stokely99-m stannous pyrophosphate myocardial scintigrams.

Acute subendocardial myocardial infarction in patients. Its detection by Technetium

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1975 American Heart Association, Inc. All rights reserved.

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