1) The study evaluated the prognostic value of routine noninvasive testing (stress thallium-201 imaging, echocardiography, radionuclide angiography) one year after cardiac transplantation. 2) Survival rates were high, with 81% surviving 5 years after transplantation. Stress thallium-201 imaging and echocardiography were predictive of survival, but radionuclide angiography was not. 3) By multivariate analysis, stress thallium-201 imaging was the only significant predictor of survival after transplantation.

1. JACC Vol. 2X. No. I IA3
July I YY6:It&Y
HEART TRA!!SP~TATION
Prognostic Value of Noninvasive Testing One Year After Orthotopic
Cardiac Transplantation
PATRICK I’. A. M. VERHOEVEN, MS,’ FORRESTER A. LEE, MD, “ACC. TARIK M. RAMAHI. MD.
KENNETH L. FRANCO, MD, FACC. CARLO!% MENIXS DE LEON. PHD, JOAN AMATRUDA, RN,
NOREEN A. GORHAM, RN, JENNIFER A. MATTERA, MPH, FRANS 1. TH. WACKEHS Q FACC
New Haven, Come&w
Ob+ves. We sougbl lo evaluate the prognostic valoe of Rpsul%. The 5-year iunival rate after cat&c trdnsptaotation
routine aoniovasive lesting-slress lballium-201 imaging, rest was 81%. By unka-hlc anal>& ,, +&rirurd@aphy @id-square
twwdimeasional et.bocardiograpby and rest equilibrium radionu- 9.211 aud stress lkallium-201 myacardiil perfiasioa imaging (cbi-
elide aag@npby-1 year after cati lrauspkmtalioo. square 16.76) were prrdiaie for survivat, wbemas rest equilii
lfaekpuad. Corouury artery vascutopatby is the most imv rium mdiiudii aq#gapby wav aoL Ctiaical rxmlriklors to
taut cause of late death after orhlopk cm&c lraosplaatalion. sorvival were dooor age tcbi-square 456j, nsm!rer of tiuman
Several clInkal variables have beeu kleutified as risk factors for leukocyte aaligen mismalcbes (cbi-quare 3.06) aad cokl iscbemic
develupmeot of conumry vasculopalky. Traditional aooiovasive time (ebbsquare 3.23). By moltivariale analysis, stress nyocardii
diagnostic testing has been sbmvn to be relatively insensitive hr iknmyug7ema$ed lbe oufy s&i&au1 predii of suhval (risk
ideolifyiug putieols wilb au@ograpbii wlby. : coaWeoce bllenal8.05 lo 0.89).
II&&J&. Restdls of prwspsrtively acquired uooiavasive tesliq co-. Normal lbaBii201 slmss myocwdhl f&ilsii
iu 47 conseeulive lra5splanl recipients aliie 1 year after lrans- buugiog I year after canlioc lraasplaalalioa is an iupmtal
pbwlalion were related lo subsequent suhvaf. Olber clhicaf prediklor of +ar survival.
v* previousfy shown to be associated wilb tke developmeat (J Am cdl #niid 1996;28:183-9)
of corouary artery vasculopatby were also included in lbe analysis.
Detection of cardiac allograft vawlopathy is a major concern cardiac transplantation (2). During the past decade numerous
in the follow-up ot patients who have undergone heart trans- investigators have explored the value of traditional diagnostic
plantation. Although infection and re,ection are the most methods to identify cardiac allograft vasculopathy. These
common causes of death in the immediate postoperative studies suggested the relati>e insensitivity of noninvasive diag-
period (1,2). coronary vaqulopathy is the most important nostic imaging for the detection of angiographic manifesta-
cause of late death. Identification of subgroups of cardiac tions of cardiac al&raft vasculopathy (6,8-13).
transplant recipients at high risk for the dalopment of The purpose of the present stu$ was to investigate the
clinically significant vasculopatby has been eI&e. Coronary prognostic value of routine noninvasrve testing. such as rest
angiography has been shown to be relatively insensitive for the equilibrium tadionuclide angiography. rest echocardiograpby
detection of the characteristically diffuse dndings of cardiac and stress myocardial pctiion imaging. for predicting sur-
allograft vasculopathy (3-7). In Contras!, most traditional vival after cardiac transplantation.
therapeutic interventions for obstructive coronary atherorle-
rosir are not effective in treating cardiac aliograft vasculopathy;
the only treatment available for advanced disease is repeat Methods
Patieuts. Consecutive patients who suwived for at least i
year after orthotopic cardiac transplantation are he subjects of
From the Departments of Intemai Medii (Se&n of Cardioascular this study. Since 1988 it has become standard procedure at
%kdiine), Diagnostic Radii (Cardiilscular Huckar Imaging Laboratoxy)
snd Epidemikgy and Pubiic Health. Yale Univenity School of Mediine. Yew Yale-New Haven Medical Center to perform multiple csnin-
Haven. Connedi~. This study war supported in pan by a ganr frcm the vasive testing proceduresrest equilibrium &iiuctide an-
Foundation “De Dric fiben.” L&den. l’k Netherfar&. giography. rest two-dimensional e-r& and quan-
Mamncript &ed October 17,199S; revised manuscript received Fe!xuary
9.19%. accepted Fclmay 21.1996. titative thallium-201 stress myocardial perfusion imaging-in
all cardiac transplant recipients at annual follow-up visits. A
total of 47 transplant recipients survived at least 1 year after
transplantation and had prospectively acquired noninvasive
testing. There were 38 men (SlcC) and 9 women (19%). Mean

2. JACC Vol. 28, No. 1
184 VERHOEVEN ET AL
July 1!?96:183-9
THALLIUM-201 IMAGING AFI’ER CARDIAC TRANSPLANTATION
recipient age vjas 46 t 10,years(range 15 to 62) at the time of the atria were considered normal observations in the ortho-
transplantation. Wleandonor age was 27 2 lo years (range 14 topic transplanted hearts (17).
to 47). All patients had standard triple-drug therapy with Rest two-dimensional echocardiography was performed
azathioprine, cyclosporine and prednisone. All but four pa- with the patient in the left lateral decubitus position using an
tients were weaned from steroids by the end of the first year. Acuson 128 Xp or HP 1500echocardiographic imaging system.
Thirty-six recipients received monoclonal antibody therapy Each patient was examined in two orthogonal views from
(OKT3) in the early posttransplantation period or as rescue paras:,inal and apical windows. Echocardiographic studies
therapy for resistant rejection. Four patients received antilym- were evaluated fu the presence of regional wall motion
phocyte globulin. Beginning in 1991, intravenous ganciclovir abnormalities. Although left ventricular ejection fraction was
therapy was given as a prophylaxis against cytomegalovirus routinely estimated from echocardiographic studies, these data
infection in all patients, except when the donor and recipient were not included in the present analysis because in our
were seronegative for cytomegalovirus. No rigorous attempts urstitution equilibrium radionuclide angiocardiography is con-
were made to treat lipid abnormalities during the first year ridered to assessradionuclide-computed lett ventricular ejec-
after transplantation. tion fraction more precisely than echocardiography (lb).
Patient data base. Clinical, noninvasive and invasive diag Echocardiography was considered abnormal if regional wall
nostic testing data were entered prospectively in the Yale-New motion abnormalities were visually present. Paradoxic septum
Haven Heart Failure and Cardiopulmonary Transplant Center motion and dilation of both the atria were considered normal
observations in the orthotopic transplanted heart (17).
data base. Selected clinical variables were extracted from the
Thallium-201 stress myocardial perfusion imaging was per-
data base and categorized as dichotomous data: gender: recip-
formed after symptom-limited treadmill exercise using a mod-
ient age >45 year; donor age >35 year; clinical history of
ified Naughton protocol. End points for exercise were angina1
diabetes mellitus, low density lipoprotein/high density lipopro-
symptoms, 22 mm ST-T segment depression 0.08 s after the J
tein ratio >3.5, low density lipoprotein >160 mg/dl, recipient-
point, ventricular arrhythmia, fatigue, dyspnea or hypotensive
donor ABO blood type identity, cold ischemic time of donor
blood pressure response. Before, during and after exercise,
heart >160 min, cytomegalovirus serologic status of recipient IZlead electrocardiograms were recorded. At peak exercise,
before transplantation, cytomegalovirus donor-recipient mis- 2.5 mCi of thallium-201 was injected intravenously and the
match, presence of cytotoxic anttbodies; antilymphocytic ther- patient was encouraged to exercise for at least 1 min longer.
apy (OKT3 and antilymphocyte globulin), total number of Four patients who were unable ;o perform physical exercise
tissue-type mismatches at human leukocyte antigen (HLA)-A, had dipyridamole coronary vasodilation in conjunction with
HLA-B and HLA-DR loci (>3 mismatches), recurrent rejec- thallium-201 myocardial perfusion imaging. These patients
tion episodes (>2 episodes) and time to first rejection episode. received a total of 0.57 mg!kg of dipyridamole over 4 min.
In addition, cardiac angiography and endomyocardial biopsy When feasible, patients performed low level exercise to de-
report data, as well as verbatim reports of all noninvasive crease subdiaphragmatic radiopharmaceutical uptake. Thallium-
diagnostic test results, were available in the Yale-New Haven 201 was injected 4 min after completion of dipyridamole
Hospital Diagnostic Imaging Database. infusion.
Noninvasive testing. Rest equilibrium radionuclide angio- Planar myocardial perfusion imaging was performed using a
cardiography was performed using the modified in vivo Iabel- computerized gamma camera equipped with a low energy,
ing method with 20 to 25 mCi of technetium99m pertechne- all-purpose, parallel-hole collimator. Imaging was performed
tate (14). ‘Ihe gamma camera was equipped with a parallel- in three projections: supine left anterior oblique, supine ante-
hole, general all-purpose collimator. The energy window rior and right side decubitus left lateral. The energy window of
(20%) was symmetrically placed over 140 keV. Images were the gamma camera was set over the thallium-201 68-keV x-ray
obtained in three views: left anterior oblique, anterior and left peak (25% windowj. All images were acquired for at least
lateral. Data were acquired in electrocardiographic synchro- 8 min, accumulating at least 600,000 counts in the field of view.
nized frame mode (16 frames per R-R cycle) on computer in a Delayed imaging was performed 2% to 3 h later in the same
64 X 64 matrix (word mode) for a total of 5 million counts. projections and for the same time. Quantification of the
Left ventricular ejection fraction was calculated using pre- thallium-201 images was performed as described and validated
viously validated, automated edge-detection software (15). A previously (18-20).
varying left ventricular region of interest and cycle-.lcpt,dent Stress thallium-201 myocardial perfusion imaging was con-
background region were used. The background corrard sidered abnormal if myocardial perfusion abnormalities (either
volume curve was filtered to four Fourier harmonics. Left reversible or lixed) were present on stressimages by quantita-
ventricular ejection fraction was determined from the fitted tive circumferential count distribution profile analysis.
curve in the usual manner. Biopsy and coronary angiograpby. Endomyocardial biopsy
Equilibrium radionuclide angiocardiography was consid- and cardiac catheterization were performed according to start:
ered abnormal when the left ventricular ejection fraction was dard techniques. Ty@ally, a total of sii endomyocardial biopsy
lower than 50% or when regional wall motion abnormalities specimens were obtained. Rejection grades were defined ac-
were reported Paradoxic septum motion and dilation of both cording to the International Society for Heart and Lung

3. JACC Vol. 28. No. 1 VERHOEVEN ET AL. 185
July 19%:183-9 THALLIUM-201 IMAGING AJTER CARDIAC TRANSPJANTATJON
Transplantation: grade 1 = mild rejection; grade 2 = moderate Table 1. Clinical Character&in of 47 Transplant Recipients
focal rejection; grade 3 = moderate rejection. After the biopsy, Recipient
right and left heart catheterization was performed in multiple Age W 46.1 i 9.5
views. Coronary angiograms were interpreted visually by expe- Rallge 15-62
rienced angiographers immediately after cardiac catheteriza- Male gender 18 (81%~
Race
tion. Quantitative coronary angiography was not performed
white 41(8&l%)
routinely. Reported findings of “distal tapering” in the coro-
Black 2 (8%)
nary arteries were not considered to be reliable because results Hispanic 2 (4%)
of noninvasive stresstesting were usually known at the time of Diabetes 12(26%)
coronary angiography. Only distinct focal abnormalities were Lipid levels
entered in the data base. For purposes of this study, coronary LDLHDL 3.03 -z 1.2!
angiography was o+Aered abnoi& if one or more discrete LDL (mpdl) 130 f 38
or tubular stenoses were reported. CMV positive (pretranspant) 13 (2%)
CMV mismatch (donor positive. recipient negative) 9(19%)
Folhwp. The reports of yearly posttransplant noninva- Donor
sive and invasive examinations were retrieved from the data 26.8 2 95
hge w
base and categorized by year of follow-up by one of the authors Range 14-47
(P.V.), without knowledge of the patients’ subsequent clinical Cold khemic time (min) 161 r46
status.Original clinical reports representing the impressions of Range 50-260
the interpreting physicians at the time of noninvasive testing, Clinical
Antil~mphcqic therapy 40 (mi )
unaware of the future clinical outcome of the transplant
Time to first rejection (wk) 6.7 f. 5.6
recipient, were used. Although other noninvasive diagnostic
Range I-30
imaging modalities may have been performed in the interval Treated rejection episodes I .2 I 0.9
between the yearly follow-up visits, these data were not Range i-3
considered in the present analysis. The analysis is focused on HLA mismatches 4.6 + I .2
the test results 1 year after transplantation. Autopsy reports of Range O-6
patients who died after the first year following transplantation ABD identity 43 (91%)
were reviewed as well. Data presented are mean value z SD, range or number (5) of patico:r.
StatisthI analysis. Dichotomized noninvasive test results AEO = ABO blood typing: CMV = cytomrgalovbus: HDL = high density
and clinical variables 1 year after cardiac transplantation were lipoprotein; HLA = human iehkgte antigen: LDL = low density lipoproteix
evaluated as potential predictors of long-term survival. In
univariate analysis, the probability of survivmg was calculated
using the Kaplan-Meier product-limited method. The log-rank Of 47 patients who survived for 1 year after transplantation,
test was used to test differences in survival curves. Because of 5 (11%) died afterward (range 13 to 47 months after trans-
the relatively small sample size, only those variables identified plantation). All five patients were men. of these deaths, four
by univariate analysis as significant predictors of survival (p < were due to acute myocardial infarction and one to infection
0.05) were considered for inclusion in multivariate Cox regres- (influenza A pneumonia). Three of the five patients who died
sion (proportional hazards) models. In the first Cox regression had angiographic vasculopathy. Autopsy was perfotmed in
model the three noninvasive test results were entered to three of the tive deceased patients. In each patient angio-
determine which ones were independently associated with graphic coronary vasculopathy was confirmed postmortem.
survival, after adjustment for those clinical variables that were Nonhwasive testing 1 year after hm~spiantation. One year
associated with survival (p < 0.10) at the univariate level. after cardiac transplantation, 45 patients (%%) had all three
noninvasive examinations, whereas 2 patients (4%) had two of
the three noninvasive tests performed. Stress myocardial per-
Results fusion imaging was performed in all 47 patients. Myocardial
Patient characteristics and follow-up. Patient characteris- perfusion abnormalities were present in seven patients (15%).
tics are shown in Table 1. No patients were lost to follow-up Three patients had 6xed defects, one patient had a reversible
after 1 year. The mean survival time of those who survived 1 defect, two patients had partial reversible defects and one
year after cardiac transplantation was 45 c 20 months (range patient had a fixed defect with reverse redistribution. Qf seven
13 to 100). The survival rate 5 years after transplantation patients with abnormal thaUium-201 imaging, four had focal
among patients who survived at least 1 year was 81% (Fig. 1). vasculopathy by coronary angiography. Rest two-dimensional
Thirty-four patients (72%) were treated for at least one echocardiography was performed in 46 patients. Wall motion
rejection episode (mean 1.2 +- 0.9, range 1 to 3). After the first abnormalities were present in three patients (7%). Two pa-
year, four recipients sustained (fatal) acute myocardial infarc- tients had dii global hypokinesis, and one patient had a
tions. Three patients had unexplained graft failure, successfully regional wall motion abnormality. Qf ‘three patients with
treated with steroids. Fiie patients had focal vasculopathy on abnormal echocardiography, two had focal vasculopathy by
angiography. coronary angiography.

4. JACC Vol. 28, No. 1
186 VERHOEVEN ET AL.
Juty 1996:180-9
THALLIUM-201 IMAGING AFTER CARDIAC TRANSPLANTATION
Figure 1. Probability of survivalfor 47 patients who
survivedorthotopic heart transplantationfor at least
12 months.Numbersin bracketsindicate number of
patientsat risk.Survival5 yearsaftertransplantationis
818.
a6 48 60 72 64 96
rro?!hs after transplantation
Rest equilibrium radionuclide angiocardiography was per- stress myocardial perfusion imaging (Fig. 2). Probability of
formed in 46 patients. Twenty-eight patients had normal survival was 94% for patients with normal rest echocardiogra-
equilibrium radionuclide angiocardiography. Their mean left phy and 33% for patients with abnormal rest echocardiogra-
ventricular ejection fraction was 61 f 8% (range 50% to 83%). phy. There was no significant difference in predicted survival
Eighteen patients (39%) had an abnormal equilibrium radio- for patients with a normal versus an abnormal rest equilibrium
nuciide an&cardiogram. Their mean left ventricular ejection radionuclide angiocardiogram at 1 year.
fraction was 42 2 5% (range 26% to 50%). Twelve patients In the first proportional hazards (Cox regression) model,
had an abnormal left ventricular ejection fraction and abnor- the independent association between thallium-201 stress myo-
mal regional wall motion; five patients had an abnormal left cardial perfusion imaging and rest echocardiography with
ventricular ejection fraction and no regional wall motion
abnormality; and one patient had a normal left ventricular
ejection fraction but apical hypokinesis. Of 18 patients with Table 2. Univariate Relation BetweenClinical and Noninvasive
abnormal rest equilibrium radionuclide angiocardiography, 4 Patient Variables and Survival (Kaplan-Meier Analysis)
had focal vasculopathy by coronary angiography. Variable Chi-Square p Value
Naninvasive testing, clinical variables and survival. Four
of 7 patients with abnormal thallium-201 stress myocardial Recipient
4% 1.27 0.26
perfusion imaging and only 1 of 40 patients with normal stress Gender 1.11 0.29
myocardial imaging died during follow-up. (The four patients Race 1.51 0.47
with abnormal thallium-201 stress imaging died of acute Diabetes 0.008 0.93
infarction, whereas the one patient with normal thallium-201 LDlfHDL 1.54 0.21
imaging died of infection.) Two of 3 patients with abnormal LDL >I60 mgidl 0.08 0.78
echocardiography and 3 of 43 patients with normal echocardi- CMV posit& 1.21 0.27
CMV mismatch 1.77 0.18
ography died during follow-up. Three of 18 patients with
Donor
abnormal equilibrium radionuclide angiocardiography and 2 of 4.56 0.03
A%
28 patients with normal equilibrium radionuclide angiocardio- Cold ischrmic time 3.23 0.07
graphy died during follow-up. Clinical
By univariate analysis, older donor age (~35 years; p = Antilymphocytic therapy 0.72 9.40
0.03), abnormal echocardiography at 1 year (p = 0.002) and Time to first rejection episode 0.35 0.55
abnormal stress thallium-201 imaging at 1 year (p < 0.0001) No. of treated rejection episodes 0.002 0.96
were significantly associated with poorer subsequent survival. No. of HLA mismatches 3.06 0.08
No. of ABO identity 0.26 0.61
Cold ischemic time (>160 min; p = 0.08) and the number of Noninvasive testing
human leukocyte antigen mismatches (>3 mismatches; p = ERNA 1.22 0.27
0.07) showed a borderline significant association with survival. Echocardiography 9.21 o.cm2
Table 2 summarizes the results of univariate analysis, Proba- Stres thallium-201 imaging 16.76 0.fnlO1
biIity of survival 5 years after transplantation was 97% for ABO = ABO blood typing; CMV = cytomegaloviros; ERNA = equilibrium
patients with normal thallium-201 stressmyocardial perfusion radioouclide aogiocardiiphy; HDL = high de&y lipoprotein; HLA =
imaging and 26% for patients with abnormal thallium-201 human leukocyte antigen; LDL = low de&y lipoprotein.

5. JACC Vol. 28, No. 1 VERHDEVEN ET AL. 187
July 199fxIR3-9 THALLIUM-201 IMAGING AFTER CARDIAC TRANSPLANTATION
Figure 2. Probability of survivalin patientswith nor-
mal andabnormalstress thallium-201(Tl-201) imaging
at l-year follow-up (n = 47). Dashedline represents
survivalfor patientswith normal thallium-201imaging
(n = 40). Continoolis liw represents survival for
patientswith abnormal thallium-201imaging (II = 7).
Numbers in bracketsindicate number of patientsat
risk. Patientswith abnormal stressthallium-201 imag
ing havea significantly(p < 0.0001)worsesurvivalrate
than patientswith normal SIWES thallium-201imaging.
survival was tested (rest equilibrium radionuclide angiocardio- years and SO% at 5 years (1,2,21.22). Because of the diffuse
graphy was not included in the model because it was not nature of the disease it is concehable that the presence and
predictive of survival at the univariate level). As shown in severity of coronary artery vasculopathy are underestimated by
Table 3, normal thallium-201 stress myocardial perfusion routine angiography (3.23). Recent studies with intracoronary
imaging 1 year after transplantation was the only significant ultrasound suggest that vasculopathic intimal thickening oc-
independent predictor of survival (relative risk [RR] = 0.27; curs frequently in cardiac transplant recipients (24).
95% confidence interval [CI] 0.06 to 0.89). The results of the Several clinical variables, such as rejection (U), cytomega-
second proportional hazards model indicate that normal thal- lovirus infection (26), recipient gender, recipient age, donor
lium-201 stress myocardial perfusion imaging 1 year after age (27), history of diabetes mellitus (28), and fasting serum
transplantation remained significantly associated with survival lipoproteins (29), have been identified to be associated with
(RR = 0.19; 95% CI 0.03 to 0.60) when controlling for donor the development of vasculopathy and adverse outcome. Per-
age, cold ischemic time and number of human leukocyte haps owing to the relatively small number of patients, these
antigen mismatches (Table 4). variables were not signihcantly related to survival in the
present study. Only donor age was a significant predictor of
survival by univariate analysis,but not by multivariate analysis.
Discussion Cold ischemic time and the number of human leukocyte
This study focuses on the prognostic value of routine antigen mismatches only approached statistical significance in
noninvasive testing 1 year after orthotopic cardiac transplan- univariate analysis in the present study.
tation. In multivariate analysis, normal stress myocardial per- Previous studies usually focused on the value of traditional
fusion imaging at 1 year is the single most important predictor noninvasive testing to identify cardiac allograft vasculopathy.
of long-term survival after heart transplantation. The proba- These studies generally suggested a relative insensitivity of
bility of survival 5 year after cardiac transplantation for noninvasive diagnostic imaging to detect an&graphic mani-
patients with normal stress perfusion imaging at I year is 97%. festations of cardiac ahograft vasculopathy (6,8-13). Smart et
The development of coronary artery vasculopathy after
cardiac transplantation is recognized as an important limiting
factor for long-term survival. Tbe angiographic incidence of Tabte 4. Relation of StressThallium-201 Imagingto SurvivalAfter
vasculopathy has been reported to be 14% at 1 year, 37% at 3 Transplantation(Cox propxtlonal hazards), Adjusted for Donor
Age. Number of Human LeukocyteAntigen Mismatches Cold and
IsehemicTie
--
Table 3. Relation of StressThallium-201 Imagingand Rest Risk 95% cintkkwe
Echocardiogrape to SurvivalAfter Transplantation(Cox Variable Ralio Interval fJ$-Q~c p
Value
proportional hazards),Adjusted for the Other Test - Stress thallium-Bl 0.19 0.031-0.60 8.14 0.0043
Riik 95%CFnfidenee P ~4%
Variable Ratio Interval cbi-square V&l‘2
Donor as I .02 0.87-IS7 um 083
Stres5tbaUium-2u1 0.3 0.06-0.1 4.61 0.03 Cotd iscbemic time I.00 0.9w.o ct.17 0.68
imaging HIA olismatches 0.77 0.30-2.70 0.23 0.63
Fsbmrdiihy 056 0.17-1.77 1.03 031
HIA = bumui leukocyte aatigee

6. 188 VERHOEVEN ET AL. JACC Vol. 28. No. 1
THALLIUM-MI IMAGING AFR CARDIAC TRANSPLANTATION July IWh:IRJ-9
al. (8) reported that rest regional walr motion abnormalities References
and depressed left ventricular ejection fraction by two- 1. Ciao S, Schroeder J. Alderman E, et al. Clinical and laboratory correlates of
dimensional echocardiography were more sensitive than accelerated coronary artery disease in the cardiac transplant patient. Circu-
kllium-201 stress myocardial perfusion imaging for the de- lation 1987;76 Suppl V:V-S6--61.
2. Gao S. Schroeder J, Hunt S. Stinson E. Retrensp!nntation for severe
tection of coronary vasculopathy. accelerated coronq artery disease in heart transplant recipients. Am J
In the present study the prognostic value of long-term Cardiol 1988;62:876-81.
survival as determined by noni&asive testing was evaluated. 3. Ciao S, Alderman E. Schroeder J. Silverman J, Hunt S. Accelerated coronary
vascular disease in the heart transplant patient: coronary atteriographic
Rest left ventricular ejection fraction by equilibrium radionu- findings. J Am Coil Cardiol 1988;12:334-40.
elide angiocardiography was not a significant predictor of 4. Keogh AM, Valantine HA, Hunt SA. ct al. Impact of proximal or midvewl
dircretr coronary artery stenoses on sun&! after heart transplantation.
long-tern? survival. This can be explained by the relatively J Heart Lung Transplant 1992:11:89?-901.
narrow range of left ventricular ejection fraction values at the 5. Stovin PGL Sharples LD, Schofield PIM, et al. Lack of association between
l-year follow-up examination. Most patients had a left ventric- cndomyocardial evidence of rejection in the first six months and the later
drvelopmcv of trar.spl:nt-rcl&ed cownan, artery disease. J Heart Lung
ular ejection fraction >40%. The Jikrcnlial predictive valoc Transplant 1993:12:llU-6.
of leri ventricular ejection fraction for future cardiac events in 6. Hosenspud JD, Shipley GD. Wagner CR. Cardiac allograft vasculopathy:
patients with coronary artery disease is less in the normal range current concepts, recent developments, and future directionr. J Heart Lung
Transplant 199?;11:9-23.
than in the abnormal range (30). It is conceivable that assess-
7. O’Neill BJ, Ptlugfelder PW, Singh NR, Menkis AH. McKenzie FN, Kostuk
ment of left ventricular function by stress equilibrium radio- WJ. Frequency of angiographic detection and quantitative assessment of
nuclide angiocardiography or stress echocardiography (31) coronary arterial disease one and three years after cardiac transplantation.
Am J Cardiol 1989;63:12?1-6.
would have comparable predictive value for survival as shown
8. Smart FW. Ballantvne CM. Cocanoueher B, et al. Insensitivitv of noninva-
in the present study by stressmyocardial perfusion imaging. sive tests to detect coronary artety vas&lopathy after heart transplant. Am J
Stressmyocardial perfusion imaging was a strong predictor Cardiol 1991:67:243-7.
9. Kemkes BM, Schutz A, Engclhardt M. Brand1 U, Breuer M. Noninvasive
of 5-year survival. Of five patients who died, four (80%) had methods of rejection diagnosis after heart transplantation. J Heart Trans-
abnormal stressthallium-201 myocardial perfusion imaging 1 plant 199?;ll:S221-31.
year after transplantation. In contrast, only 3 of 40 (8%) 10. Richter J, Hcrreros J. Serena A. Damper M, Ramirer JC, Arcas R. Thallium
scintigraphy in human transplants: a way to detect myocardial damage.
patients alive at 5 years had abnormal stress thallium-201 J Heart Lung Transplant 1991:10:33-7.
imaging. Probability of survival 5 year after cardiac transplan- 11. Smart FW. Grinstead WC, Cocanougher B, et al. Detection of transplant
tation was 97% for patients with normal stress myocardial arteriopathy: does exercise thallium scintigraphy improve noninvasive diag-
nostic capabilities? Transplant Proc 19Y1;23:llXY-92.
perfusion imaging and only 26% for patients with abnormal 12. McKillop JH. Goris ML. Thallium-201 myocardial imaging in patients with
stressmyocardial perfusion imaging at 1 year. These findings previous cardiac transplantation. Clin Radio1 1981;32:447-9.
concur with those by Ciliberto et al. (32), who found a similar 13. Golitsin A, Pinedo JI. Cienfuegos IA, Chamorro JL, Ortiz Berrocal J,
Castillo-Olivares JL. Thallium-201 uptake: a useEul method for assessing
prognostic value for stressmyocardial perfusion imaging. heart transplantation. Transplant Proc 1984;16:1?6?-3.
Study limitations. The number of patients included in the 14. Callahan RJ, Froelich JW. McKusick KA, Leppo J, Strauss HW. A modified
present analysis and the number of cardiac events during method for the in viva labeling of red blood cells with Tc-99m: concise
communication. J Nucl Med 1982;23:315-8.
follow-up are relatively small. This does not allow for analysis 15. Lee FA, Fetterman R, .&ret BL. Wackers FJTh. Rapid radionuclide-derived
of subgroups of patients (e.g., patients with reversible myocar- systolic and diastolic cardiac function using cycle-dependent background
dial perfusion defects versus patients with tied defects). correction and Fourier analysis. Proc Comp Cardiol IEE Camp Sot 1985:
443-G.
Furthermore, the relatively small number of patients does not 16. Van Royen N, JatTe CC, Krumholz HK, et al. Comparison and reproduc-
allow for the inclusion of more variables in the multivariate ibility of visual echocardiographic and quantitative radionuclide left ventric-
analysis for loss of statistical power. Finally, the aim of this ular ejection fraction. Am J Cardiol 1996;77:843-50.
17. Gornan J III, Snow FR, Paulsen W, Arrowood JA, Thompson JA. Nixon JV.
study was not to compare noninvasive and invasive assessment Echocardiographic profile of the transplanted human heart in clinically well
of coronary vasculopathy. We do not routinely perform quan- recipients. J Heart Lung Transplant 1992;11:80-9.
titative contrast angiography or intracoronary ultrasound for 18. Wackers FJTh, Fetterman RC, Mattera JA, Clements JP. Quantitative
planar thallium-201 stress scintigraphy: a critical evaluation of the method.
assessment of posttransplant va@opathy. These methods Semin Nucl Med 1985;15:46-66.
may have value in predicting outcome after cardiac transplan- 19. Wackers FJTh, Gibbons RJ, Verani MS, et al. Serial quantitative planar
tation. technetium-99m-isonitriie imaging in acute myocardial infarction: efficacy
for noninvasive assessment of thrombolytic therapy. J Am Coil Cardiol
Condosions. Stress myocardial perfusion imaging I year 1989;14%61-73.
after cardiac transp!antation is an important predictor gf 20. Sigal SL Soufer R, Fetterman RC. Mattera JA, Wackers FJTh. Reproduc-
s-year survival. This could have important implications for the ibility of planar thallium-201 scintigraphy: quantitative criteria for reversibil-
ity of myocardial perfusion defects. J Nucl Med 1991;32:759-65.
cost-effectivemanagement of transplant recipients. However, a 21. Gao SZ, Schroeder JS, Alderman EL et al. Prevalence of accelerated
thorough cost atalysis is beyond the scope of the present study. coronary artery disem in heart transplant stuvivors: comparison of cycle.
Normal ih&tmQOl stress myoeardial perfusion imaging sporine and azathioprine regimens. Circulation 1989$0 Suppl IIt:ilI-100-5.
identilks a low risk group of cardiac transplant recipients. 22. Darracett-Cankovic S, Stovin PGI, Vetney GI. Wallwork I, English TAH. A
new method of detecting and monitoring coronary occlusive disease in the
Patients with abnormal thallium-201 stress imaging are poten- transplanted heart [abstract]. ! Heart Transplant 1990$72.
tially at high risk and deserve close subsequent monitoring. 23. Schroeder IS. GaoSZ, Hunt S4 Stinson EB. Accelerated graft coronary

7. JACC Vol. 28. No. 1 VERHOEVEN ET AL. 189
July 19!%183-9 T’tiALLIlJM-XII IMAGING AFTER CARDIAC TRANSPlANTATtON
artery disease: diagnosis and prevention. J Heart Lung Transplant 1992;ll: 28. Young JB. Naftel DC. Bourge RC. et al, and the Cardiac Transplant
S258-66. Research Database Group. Matching the donor and heart transplant recip
24. St. Gear FG, Pinto FJ, Alderman EL et a!. lntracoronary ultrasound in ient. Clues for succev.fwl expansion of the donor por& a multivariable,
cardiac transplant recipients. In viva evidence of “an&graphic silent“ multiinstitutional study. J Heart Lung Transplant 1994$3:353-65.
intimal thickening. Circulation 1992;85:979-87. 29. Kobashigawa JA, Katznelson S, laks H, et al. Effect of pravastin on
2.5. Uretsky BF, Murali S. Reddy PS, et al. Development of coronary artery outcomes after cardiac transplantation. N Engl J Med 1995:333:621-7.
disease in cardiac transplant patients receiving immunosuppressive t!xqy 30. The Multicenter Postinfarction Research Group. Risk stratification and
with cyclosporine and prednisone. Circulation 1987;76:827-34. survival after mycxardial infarction. N Engl J Med 198X309:331-6.
26. Grattan MT, Moreno-Cahral CE, Stames VA. Gyer PE. Stinson EB, 31. Derumeaw G, Redonnet M. Mouton-Schleifer D. et al (Vacomed Research
Shumway NE. Qtomegalovirus infection is awxiated with cardiac allograft Group). Dobutamine stress echocardiography in orthotopic heart trawplant
rejection and atherosclerosis. JAMA 198Y;261:3561-6. recipients. J Am Call Cardiol 1995;24:166.%72.
27. Wahlen T, Crcmer J, Fieguth HG, et al. Donor heart-related variables and 32. Cilibeno GR. Mangiavacchi M. Banfi F. ct al. Corona? artery diww after
early mortality after heart transplantation. I Heart Lung Transplant 19% heart transplantation: non-invasive evaluation with cxercisc thallium scintig-
10~22-7. raphy. Ear Heart J 19(93%??6-9.