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Na 5
April 19949016-32
Olijeriiws. The prpew d Ws iiveuIIga&a woo toewAssk tie oeasresa of .dean cardiac a In (svdae dWk osnfaW
practicality d eiortdam predictive value otwo lgecmdW myeewdal iduedon, "now molopleer am" surgery or
pevlliam he" with kdmedoaofm dmlbl in mcpsey B-7 dremin(yeY).
room patient' win typkd angles and a normal ar aenRgamtk Read,. tralvalaet prod oss d cardiac crab metal d de
dedromrdbpm (EGG). peaeam d three or mew cwan ry room Bean (p - 0.009, elk
Bahglveed. Aemraq d merpaey swam tans PRIM amen ratio 3.g mad as damormal or ogahoml sec tdtm ilinumm
meat may be Improved when clinical and ECG vselhke an meal ramlbi nma (p =1.d01, risk ratio 131) . M.Blvmide wpw-
h Conjunction wide Mite *d1mmj 1 mpesmdY peefhtiw dm ambeis Identified r ahnmd peetedm range m lie 6dy
Imaging. Tedmedmrfpm amadhi k a see, nallobdoper tied Is hdepmded pride dadvmn madiae crew (Illm 0Aflf). Of
taros up by de myoarBam is pmpseka to Well flew, let 78 patiar win a am" pflde . roa, only 1 lad a madjust
mpka tallmrd01, it raWhiwtm slangy dam lejeetla .. eras ampmed web is prisms Wish equip d area a 17
TeehrethmJ9mamtdbi mm dm be Injected dmhp they pair, pad" will alaonsid ova, wed a cardiac treat sets of 1390
d bop agahad I to 2 h hear (when peeress have been sad 71%, respectively (p - L11111161).
diulenI r.bawa) will cedrm whether aha .einnl w ofpers Cam/ata. Initial nyecaril perfusion Im{hg with
des were present at tier times of hidecdon . amlmdk.Alm .rbmibi when qipile h emmpaq ram pr
dhdmde. One hie,d ed two a gall room patients win tame we gpkd won d ∎ aoomeI or amdkpmWr Et G
typical mom (on the book d ∎ standardised lyha gnmehs- missiles to be bb* aonnrate le dkffmuMbg' law said
mire) and ∎ normal er needhpedle ECG Wd a hdiadm *m Wills IM sabjects.
seeIMrill y)adkn durbrg gmphms sail wen fellewad ap fw G As Cai (adW 1f9dd3:1Nd-22)
The emergency room evaluation of chest pain is a frequent TechmduntA9m sedmlbi is a new rialkhosop that Is
and troublesome problem. Accurate evaluation is made take
. up by die myocardium in proportion to blood flow . It has
difficult by the low specificity of standard clinical and a prolonged retention in the myocardium and redkblbwes
electrocardiograpihic (ECG) variables (1-3) . The come minimally after injection (23). That, teclmdism-9m cam&
qucnccs of inappropriate emergency room discharge of Can be i*cted wide patina are acutely symptomatic . and
patients with true myocardial Infarction may be serious (4,5). losses acquked 1 to 2 h later (when pelican have been
Thus, most physicians practice a conservative admission c iniealy stabilised) Will mission whether Profusion ebnorms4
policy that results in a high Ievel of intensive can admissions irks were posed at the time of itdection (16-18), In the
of patients with noncardiac chest pain (6 .7). current Investigation, we sought to determine whether acute
Previous studies have used computer algorithms (8,9), myocardial peAbdon imaging with technetium-99m seaa-
two-dlcleeaional echocardiography (10,11), thalium-201 (12- mibi could accurately distinguish between low and high risk
1s) and technodum-PPm sesteodbi (16-22) to improve diagnos. emergency room patients with typical aopm and a normal or
to accuracy and risk assessment . However, most studies have nondiagoaic I;CO. Additionally, we sought to assess what
used broad inclusion criteria . Including patients with typical or if any incremental predictive inn emation was provided by
mypkelchest pain and with dkgnosdcor andisgnostic ECGs. initial technetium-99m seitkmibi imaging compared with
combinations of clinical and ECG variables .
F. the Dammed d Nudew Cudiol y. SI . Luke's Hogdel, leek-
rov9Ia FWW . TN. eddy *as supposed in pays by g ma fine Do post
Mack Pbuuaeudcol Cmpmy. Npah BBWWWce. Msemcauatswd Syocw
Rad9.phaymar,med aee.oy, Chtoweab . Csetea Methods
Mmsmpt received Apt 29 .1990; revised osnnaipl received NovemW Patient selection. The study group comprised 102 patients
ber 22, 1M. accepted December 1 . 1993.
Add,.re her n..~.emd•"es : Dr. 7be,ew C. ohm, 4105 Bdfon Rod, seen in the emergency room for evaluation of ongoing
Suite 2065 . Jackmav0a. Florida 32216 . agirmaike chest pain who had a normal or nondiagrwstic
12-lead ECG and underwent acute technetium-99m sesta- were categorized es normal or abnormal (bat nordiagnostic) .
mihi imaging
. Technetium-tpm sestamibi imaging was per- Most abnormal (hut mmdiagnostic) ECGs had nonspecific
formed when requested by the referring physician for clinical ST-T wave charges or bundle branch block. Normal (low
reasons. Chest pain was semigimntilatirely analyzed using a risk) ECGs were compared with abnormal but nondiagnostic
modification of a previously validated chest pain score (24) (higher risk) ECGs for predictive value. Follow-up ECGs
(see Appendix) and only patients with typical angina pectoris were obtained in 97 patients and analyzed for additional
(prospectively defined as a chest pain score a4) were predictive value.
included. Patients were not included if there was historical Clinical end paints. End points were prospectively de .
or ECG evidence of previous myocardial idarction . Patients hiked as prehospital discharge cardiac death. nonfatal myo-
with atypical chest pain, ECG evidence of ischemia (ST cardial infarction or the need for immediate coronary inter-
segment elevation. >_ I-nor ST segment depression or new T vention (coronary artery surgery . coronary angioplasty Or
wave Inversion) or contmindicatlons to !sdionuclide imaging coronary thrombolysts) . Seventy-nine patients were admit-
were also excluded. Of screened patients who were consid- ted to hospital. Twenty-three (23%) of 102 enrolled patients
ered eligible <Ill% were not carolled because of lack of were discharged from the emergency room . These patients
available isotope . These patients had baseline clinical and were younger (44 t 11 vs . 52 ± 12 years [mean ± SDi . p
ECG characteristics similar to carolled patients . O.OOB) and had fewer risk factors (1 .4 ± 1 .2 vs . 2 .1 ± 1 .1 .
Technique. All patients had a 12-lead ECG and bolas p = 0.01) than patients admitted to hospital but otherwise
[gjection of 10 to 30 mCi of technetium-99m sestamibi while had similar baseline clinical and ECG characteristics . Late
they were acutely symptomatic . To ensure that radioisotope follow-up of these patients (including a limited history (23
was available for injection after ecrmal operational hours of patients] and 12-lead ECG [15 patients] m >90 days) re-
the Department of Nuclear Medicine. two pee nixed slats of vealed no adverse cardiac events or readmission for recur-
techaetena-99m sesmmtbi were available for emergency rent symptoms .
room use between B AM and midnight (morning and after- Statistical methods Statistical associations between ad-
noon viols). The morning vial was calibrated for 30 mCi at verse cardiac events and discrete variables were tested by
noon and the afternoon vial far 30 mCi a! 4 PM. This allowed chi-square analysis. Associations between cardiac events
10 mCi of technetium-"m restamibi to be available far and continuous variables were analyzed with independent
injection until stidnigla . Thus. at teax out premixed vial was r tests and univasiate linear regression analysis. Univariate
available for initial imaging between B AM and midnight variables significantly (p <_ 0 .05) associated with adverse
7 daystweek. Favergen^y room physicians completed a cardiac events were examined for eofimeority and entered
course in radiation safety, and radioisotope administration into a multivariate regnsioa equation.
was prrfmmed miler supervision of the emergency room
physician to ensure ute(-.in, during symptoms . Subsequent
Remits
to radieisompe Injection, patients were given appropriate
ant[dsehemiclantiaoginal lento . After stabilization of Clinical dmratmistira . Clinical charactetiatia, including
symptoms patients were transferred to the Department of age. chest pain score, most coronary risk factors and use of
Nuclear Medicine for imaging . Inmost patients imaging was certain cardiovascular medications, such as digitalis. anti-
performed <60 mm alter igjeetian (mean time [
. 8D] 54 a . anticoagulant or antianginal therapy, were evenly
platelet
17 min, range 30 to 110) . Perfitaan houses were obtained in distributed between patients with and without cardiac events
a IV arc over bit views using 20 aiprQaction from the left (Table I). Similarly, a patient history of previous heart
posterior oblique to the right ante for oblique position and a disease, conmaty anpography or exercise test was not
siilgk.pbatan emission computed lemographic (SPECT) predictive of cardiac events . Conversely, compared with
camas equipped with a low enmgy, high resolution, paral- patients without cardiac events . patients with cardiac events
W-hole collimator. Reconstruction was performed using a had a signifiandy higher mean number of cardiac risk
Buttmwoeth filter without attenuation correction and a 20% factors (2 .5 x 1 .1 vs. 1 .8 ± 1 .1, p = 0.04) . a greater
symmetric energy widow centered on 140 keV . The images prevalence of abnormal (but eondis®wstic) ECGs, were
were rend immediately by a Scented expert nuclear cardiol- more often men and had a slightly higher chest pain
ogist Or Iadlaloejat, and preliminary results were reported to scale .
the attending physician . Images were subsequently analyzed Chains] risk groups . i n an effort to replicate clinical
and soared by a consensus of two readers who were unaware judgment, patients were stratified into low, intermediate and
of clinical chmaeteristics . ECG results and outcome . Studies high risk groups on the basis of coronary risk factors (<3 vs.
were categorized as normal (low risk), abnormal (sigh risk) a3) and their ECGs (normal vs . abnormal but nondiagnostic)
or equivocal (intermediate risk) by visual qualitative amly- (fable 2) . Low (33 patients), intermediate (46 patients) and
is. high (23 patients) risk patients by these clinical criteria had
Qualifying ECGs were interpreted by one of the in- respective cardiac event rates of 6%, I t% and 35% (p =
veslgamrs who was unaware of clinical characteristics, O.0D7) (Fig . I). Combining the intermediate and high risk
technetium-99m sestamibi results and outcome . The ECGs groups and comparing them with the low risk group revealed
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tllal inters teats (oval accuracy 71%. p = 0 .01). Thirty-two compared wish 3 (25%) of 12 with a normal scan, had
patients underwent prehospital discharge comar9 and- significant (>70%) coronary artery disease (p = 0.01). Sig-
Tophy . Founeeo (70%) of 20padeds with= abnormal scan . nificant coronary artery disease was evenly distributed be,
tween the haft anterior descending (39%) . left circumflex
(32%) and right (32%) coronary arteries
. Of the 32 patients
ihkb 4. Comparison d Smddvhy. Specificity and Overall who underwent cardiac catheterizat(on, 8 had anterior per-
Mmacy d Nigh m hstmndiale Clinical Risk Shims' Versus fusion abnormalities, and of these 6 had significant left
Abnormal or Egdvxd Tahoetoa-99m Sesteen'6i Raubs in anterior descendingemonary artery disease (p = 0.0007) . 0f
Prediction d Cardiac Evens 4 patients with lateral perfusion abnormalities, 3 had dgnir
Overall ieant left circumflex coroary attay stea0sia (p - 0.03), and
Semidvhy SpedOelty A-y of 13 patients with inferior perfusion defects, 8 had signifi-
Clinical risk same; 111% 379 43% cant right coronary artery stenosis (p = 0.0005) .
Tedeniae89msesuabinadt 94% a% t0% Follow-up. Follow-up, including limited history (94 pa-
pYdu NS 0.mm 0.0001
tients) and I2-lead EC0 (32 patients) was performed at least
-so T" 2. 9o days after initial imagigg . One patient with a positive scan
underwent coronary angioplasty 5 weeks afterdischarso . No segment elevation at rest (27). Rest angina with ST segment
late events occurred in patients with normal soaps . depression or normalization of negative T wares is associ-
Ualvariate rapessleu analysis . Univariate regression ated with more localized subendocardial perfusion abnor
analysis ofclinical, ECG and nuclear scintigmphic variables malflles (28). However, there are logistic problems associ-
identified the number of coronary risk factors (p = 0 .04) and ated with the use of thallium-201 in acute isehemic
tochnetiumA9m sesteadbi scan results (P = 0 .0004) as pre- syndromes . Because thallium-201 redistributes after bdea
dictors of adverse cardiac events . Technetium scan results tom. optimal diagnostic accuracy requires that isotope iojec
(p = 0.001) and chest pain acme (p = 0 .05) were significantly tion and image apttdsition be performed while patients are
associated with myocardial infarction . symptomatic_ This may reduce the safety of the technique.
MWdnrite mucelen amiss. Significant (p s 0.05) Some investigators have suggested that diagnostic accuracy
univariale predictors ofadverse cardiac events were entered is not affected when thallium-201 injection is delayed after
into a multivariate wipessiou equation to assess their inde . chat pain (15) . Other studies of initial nuclear scintigraphy
pendent predictive value . Multivariate regression analysis have demonstrated decreased sensitivity when radioisotope
identified an abnormal techmriurnA9m scetamibi scan as the injection is performed after resolution of symptoms (16) .
only independent predictor of adverse cardiac events (p - Also. because thallium-201 requires a cyclotron for its pro-
0 .009). Both techoetium-99m eesmmibi and age were predic- duction, it Is impractical to keep doses available for an
tive of myocardial infarction (p < 0 .05) . unpredictable number of emergency room patients. In the
current investigation, logistic problems associated with
Ihalliuna20l were overcome by using technetimo-99m set,
consist.
IDiscnon)on Tedtnelr .Am a ulaalW . IM newer isotope has pro .
Appropriate triage of emergency room patients with longed retention by the ntyocardlum and redistributes mini .
either atypical chest pain and a normal BOG or typical mally after Injection (23) . Patients can be given an Injection
angina and a diagnostic ECO is usually straightforward. dwig cardiac symptoms and them treated with anti-ischemic
Appropriate triage is more difficult in the subset of patients therapy before cardiac imaging . We believe that the high
with typical angina and a normal or nondiagnostic ECG. Tine level of predictive accuracy achieved with teehnetiwo-%n
current investigation was limited to such patients . Correct sestamibi i this study Is attributable in pan to the absence
early management of this patient subset requires a risk of significant delay between the symptoms and radioisotope
stratification process that can accurately separate the major- Injection . Additional advantages o' technetltmf99m seats .
fly of patients into low and high risk groups . In the current Erbi include a phoiaemim)on of 140 keV and more optimal
investigation, initial myocardial perfusion imaging with doemery, allowing higher dosage and superior SPECI'
technetium-99m seslamibi distinguished between most image quality. The advantageous properties of this new
(85%) patients at very low and very high risk far short-tctm isotope have been recognized in ontaagement of patients
cardiac events (<2% and >70%, respectively) . Tints, this with unstable coronary syndromes . Injection of the isotope
technique identified both a lower and higher risk group In pants with acute myacarial b Monition be Pore reperfu-
than standard clinical and ECO variables (alone and in sio therapy can define an area of risk, and repast study
combiatkm). titer therapy quantil tea myocardial salvage (17 .18,30.31).
®etrurardlegasphle and clinical variables. Previous In patients with acute myocerdil infarction and a non-
studies have confirmed the limited diagoslic and short-tern diagnostic ECG, tedusad m-99m seslamlbi allows early
predictive value of the initial ECG in acute chest pain dlagtlosis and accurate identification of the ifrerteitad
syndromes (1-3). Patients with chest pain and a normal or artery (21).
nonspecific ECG have a low risk of Srathreatanlng compli-, TcineUwasd9m dam161 Nor Ii1W haagtq i peMsass
atins but the risk of nonfatal myocardial infarction is 1098 with shunt pai. Other studies have used techtetlum-99m
to 20% (25,26) . Thus, conservative management of patients senemibi scintigraphy to asses spontaneous chest pain
with chest pain and a normal or nonspecific ECO may yield (1622) and to rule out myocardial infarction in the enter
a low mortality but may result in lost opportunity for initial 8ency room (19). These studies have ban limited by small
Intervention and myocardial salvage. sample size (<50 sutyects), loose inclusion criteria (enrolling
PrevW donor with dwmmo4Ol. Thallium-201 scintig- patients with chest pain "suggestive of myaeardii eeh .
raphy is highly sensitive i the detection of myocardial emda" [16D and delays of isotope Injection until after reso-
infarction when Isotope Injection and Image acquisition we lution of spontaneous chest pain. Nonetheless, these studies
performed early after the onset of symptoms (12). Quantita. have demonstrated high accuracy i identification of parents
Live analysis of the ncitigrams an enhance identification of with myocardial infarction . Similar to our experience .
patients with multivessel coronary artery disease (I5). The Varetto a al . (19) observed that in emergency room patients
usefulness of thallium-201 imaging in unstable angina has with a normal scan, there i a very low incidence ofadverse
also been well described (27-29) . Large transmaal perfusion cardiac events during hospital admission or after 3-month
abnormalities are seen in patients with variant angina and ST Mow-up. Indeed, in the current investigation, a significant
cardiac event did not occur in the group of patients with Appendix . Chest Pain Score
normal scans until nerdy 100 patients had been enrolled .
Sensitivity in the current investigation (94%) is highly coo-
Pdsitire
sister with the observations of Bilodeau et al . (16) and
Location
Gre.goire and Theroux (22) . Both groups reported sensitivi- Suhsternal +3
ties of 96% when initial technetium-99m sestamibi was used Preeordial +2
to diagnose acute myocardial infarction, Thus, widespread Left chest, base of neck, lower jaw, epigastrium +1
application of this technique could achieve a significant Radiation
Either arm +2
reduction in inappropriate emergency room discharge of
Shoulder, back, neck, lower jaw (arm not +I
patients with myocardial infarction. The significantly higher mentioned)
specificity (85%) of this technique compared with standard Charactcr
clinical and ECU variables will hopefully allow reduction of Crushing, pressing . squeezing +3
costly, inappropriate intensive care admissions of patients Heaviness or tightness +2
Severity
with normal scans.
Severe +2
Cosacaoslderatloos . The cost associated with acute radio- Moderate +1
nuclide seintigraphy ($600.011 in our institution) should be Associated symptoms
considered. This expense may be partially offset by de- Dyspnea +2
creases in inappropriate intensive care admissions and short- Diaphoresis +2
Nauseatvomiting
ened length of hospital slay in patients with normal acute
Previous angina history +3
perfusion scans. Such patients are candidates for expedi- (previous history of angina pectoris : associated
tious cardiac evaluation, including early stress testing (usu- with exertion. relieved by rest or relieved by
ally in <12 to 24 h) . The initial chest pain seen in such nitrvvglycerin)
patients is used as the rest or baseline image . Patients with a Nrgarire
compatible history and an abnormal scan are at significant Location
risk for myocardial infarction and may be candidates for Localized to apex -I
Character
initial coronary interventions. such as lhrombolysis or cor- Sticking . stabbing, pinprick catching -t
onary revascularization . Further study will be needed to
determine whether such patients might benefit from intrave-
nous thrombdysis .
References
Ltd of the atody. Because of limited sample size,
I . sends JE. Band DA, A®mpum D. Chahner B, 1550110,5 FJ. L- : ai the
only one event occurred in patients with a normal scan .
initial decoamdiaWam 19 predict is-hospital conplicdiae of roots
Small cell size could result In statistical error . Also, quanti- my-dial nfluction. N Engl J Med 198$312:1137-41.
tative analysis of the tomographie images may have im- 2 . Vihanueva FS tuba PJ, Afrenkteh A. Pdlork SG, Hwang LI, Kaul S .
proved predictive accuracy . but our results are very similar Value mod GpytallnpsafMSPdmotkadsufwahwlingpaliaas presealil8
m the emergency mum with a udiao-rtted symptom for detemdeay
to previous reports (16,22) in which quantitative SPECT lane-mm marimmh . Am J Cstdiol 19D2dv746-JB.
analysis was used. Moreover, qualitative analysis is com- 3 . Lee TH . Rouen GW, weuog MC . Bated DA, Cook EF, Acne- D.
GoMmm L . Sealtivay, of merit ddiet criteria far diagnoring myoean,
monly used for the interpretation of myocardial perfusion
dial iafumim abide 24 hours of hmpimBzadaa, Ann liters Mad 1917:
studies. Finally, formal analysis of cost-effectiveness was 106:181-6 .
not a put of tte current investigation but would have 4. Lee TH, Ram GW. Weaberg MC. m al. Cladml ehmrctemtics and
assured bone, of paomu with MUM myocordkd kdseoiwe sent home
obvious relevance . from the emergeney mom. Am J Cerdlo11987:m:219-20
.
Comeldaes. The present observations suggest that acute 5. LeeTH .userLW.Brand DA .leanChmdYD,et .1.Palheawhhuum
technetium-99m sestamibi imaging is a practical technique chest pain who tune cancycsay room depettmenls agmmt mcdcst
that can accurately distinguish between very low (<20) and advice . J Gm burn Mod 19119 :21-4.
6. Lee TH, Good-L. The .-my cue null trans 3: Maorial trends
very high (>70%) risk for adverse cardiac events in most and fat- direction . Ann totem Mod 1989;10807-91.
(85%) emergency, room patients with typical angina and a 7. Hall AG, Thlbmdt GE, Hbghes RA, Samett GO . Reder VA, Sheen
IL. The emme or pilau. with mspacd myucudb infmctiuo; the
noadtagnostlc ECO. Compared with clinical and ECO vad- idenriticoian of towwksk pticma for easy sander from intensive care.
shles (almne and in combination), this new technique appears N End J Mad 1910:10!:947-8.
to have significantly greater specificity and overall accuracy 8. Goodman L. Cook EF. Brand DA, m al. A compuler peanocd to predict
in the prediction of adverse cardiac events . Patients with myarmrsal infaretioe in edurueuy deportment patients with taut pain .
N EraoJ Mad 1988318 :797401.
normal scans are candidates for expeditious cardiac evaltm- 9. Potty MW. D'Agonioo an . Seam HP, Sylkowekt PA, Hoad wa. A
tiast and possible curly hospital discharge. An abnormal scan psedit ice ietrsntem to improve coronary core unit admislm pmmtees
is associated with a high risk of myocardial infarction, and in seat- hehaoia heart disuse ; a prospective mukiceider clinical trial .
N Erro I Mad 1984;7m127.1-8.
such patients may be candidates for initial coronary inter- lo. Homwita as. Margaruotk J . Immedioe detection of early high-risk
vention. pltnls with acne myocardial Infection win& two-0Imensimal electN
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