Copyright © 2000 by Lippincott Williams & Wilkins, Inc.
Vol. 69, 2354–2356, No. 11, June 15, 2000
Printed in U.S.A.
DOBUTAMINE STRESS ECHOCARDIOGRAPHY IN PATIENTS
UNDERGOING LIVER TRANSPLANTATION EVALUATION
KEVIN WILLIAMS,1JANNET F. LEWIS,2,3GARY DAVIS,4AND EDWARD A. GEISER2
Division of Cardiovascular Disease and the Section of Hepatobiliary Diseases, Department of Internal Medicine,
University of Florida College of Medicine, Gainesville, Florida
Background. Coronary artery disease has an impor-
tant impact on perioperative morbidity and mortality
in patients undergoing liver transplantation. To as-
sess the role of dobutamine stress echocardiography
(DSE) in these patients, DSE was included in the pre-
Methods. Patients under consideration for liver
transplantation underwent detailed clinical history,
electrocardiography, and echocardiography. Patients
with documented coronary disease or symptoms of
myocardial ischemia underwent angiography. The re-
maining patients with cardiac risk factors, atypical
chest pain, or age >60 years underwent DSE.
Results. These 121 patients (77 men and 44 women)
ranged in age from 34 to 73 years (mean 53). Among the
61 patients who underwent liver transplantation, DSE
was normal in 25, nondiagnostic in 34 because of inad-
equate heart rate response, and abnormal in two pa-
tients. Major perioperative events occurred in eight
patients, all with normal or nondiagnostic DSE studies
(negative predictive value 86%).
Conclusions. In patients with low to moderate risk of
cardiac disease, DSE performed as part of an evalua-
tion for liver transplantation is a poor predictor of
major perioperative events.
More than 4000 liver transplants are performed yearly in
the United States. Perioperative mortality is largely a con-
sequence of severe hemorrhagic events and cardiovascular
complications. Recent studies have reported that as many as
27% of patients being evaluated for liver transplantation
have coronary artery disease, and perioperative mortality in
these individuals may reach 50% (1–3). Reports of studies in
which dobutamine stress echocardiography (DSE) was used
for evaluation before liver transplantation have yielded con-
flicting findings (4, 5). The purpose of the present study was
to assess the safety and clinical utility of DSE in patients
undergoing evaluation for liver transplantation.
Between January 1996 and December 1997, all adult patients
under consideration for liver transplantation underwent cardiac
evaluation, including detailed clinical history, electrocardiography,
and echocardiography. Patients with ischemic or nonischemic car-
diomyopathy or severe valvular heart disease were excluded from
further evaluation. Patients with documented but stable coronary
artery disease or symptoms of myocardial ischemia underwent car-
diac catheterization and coronary angiography. All remaining pa-
tients with cardiac risk factors (including systemic hypertension,
diabetes mellitus, hypercholesterolemia or ?20 pack-years of tobacco
use), atypical chest pain, or nonspecific cardiopulmonary symptoms,
or age ?60 years were considered to have low to moderate risk for
coronary artery disease and were referred for DSE. The 121 patients
who comprise the study group underwent DSE, using standard pro-
tocol. In brief, dobutamine infusion was initiated at 5 ?g/kg/min and
increased at 3-min increments to 40 ?g/kg/min. Intravenous atropine
was given as needed to attain target heart rate. Dobutamine infusion
was terminated if any of the following occurred: (1) target heart rate,
(2) new segmental wall motion abnormality or ?2 mm ST segment
depression, (3) complex ventricular ectopy or sustained supraven-
tricular tachycardia, (4) hypotension or severe hypertension, or (5)
severe chest pain or other intolerable symptoms. Wall motion anal-
ysis was performed by an experienced echocardiographer who used a
16-segment model as recommended by the American Society of Echo-
cardiography (6). Segmental wall motion at baseline or peak infusion
was considered indicative of coronary artery disease. Statistical
analysis was performed with commercially available software,
Statistix (Analytical Software, Tallahassee, FL). Continuous vari-
ables are presented as mean?SD. Comparison between continuous
variables was made by use of unpaired Student’s t test. Comparison
of categorical variables was made by ?2analysis.
The mean age of the 121 patients (77 men and 44 women)
undergoing DSE was 53 years (range 34–73). Hepatitis C
infection and alcoholic liver disease were the most common
causes (61%) of liver failure. Major risks for coronary artery
disease, including current tobacco use, diabetes mellitus, sys-
temic hypertension, and dyslipidemias, were present in 82
The most common reasons for termination of DSE were
target heart rate achieved (in 53 patients, 44%), and maxi-
mum dose of dobutamine and atropine given without target
heart rate (in 60 patients, 50%). Peak heart rate during DSE
and percent maximum predicted heart rate attained were
significantly lower in patients taking ?-adrenergic blocking
agents (119.9?25.4 vs. 137.6?16.4 bpm, P?0.0003, and
75.7?16.9 vs. 86.3?11.7%, P?0.0009, respectively). Adverse
effects occurred in 21 patients (17%) (Table 1) and resulted in
premature termination of testing in nine (7%). The most
common adverse effect during DSE was hypotension which
occurred in nine (7%) of the 121 patients; four of these nine
were on long-acting diuretics at the time of study. No patient
required intervention other than cessation of dobutamine
Abnormal segmental wall motion at baseline or during
dobutamine infusion was detected in only two of the 121
patients (Fig. 1). In both patients, abnormalities were con-
fined to the basal and mid segments of the inferior or poste-
1Department of Internal Medicine.
2Division of Cardiovascular Medicine.
3Address correspondence to: Jannet F. Lewis, MD, Division of
Cardiovascular Medicine, University of Florida College of Medicine,
1600 SW Archer Road, P.O. Box 100277, Gainesville, FL 32610-0277.
4Section of Hepatobiliary Diseases.
rior walls. Normal wall motion at baseline and during dobut-
amine infusion was observed in the remaining 119 patients.
Of these, 52 patients achieved target heart rate and were
considered normal, and 67 failed to reach target heart rate
and were considered nondiagnostic.
Of the 121 study patients, 61 subsequently underwent
liver transplantation during the follow-up period. Twenty-
five of the 61 had normal DSE studies, 34 were nondiagnostic
(i.e. did not reach target heart rate), and two had abnormal
studies. Significant perioperative events occurred in eight
patients who underwent liver transplantation (Table 2). No
events occurred in the two patients with abnormal DSE.
Normal wall motion during DSE had a negative predictive
value of 86%, and excluding patients with nondiagnostic
studies, was 80%. No significant differences were observed in
the rate of perioperative events among patients with normal
DSE (5/25, 20%) and those with nondiagnostic studies (3/34,
9%); P?0.19 (Fig. 1).
Three of the eight patients (37.5%) with complications
after liver transplantation had prior history of cardiac abnor-
malities. One patient experiencing atrioventricular nodal re-
entrant tachycardia had a history of Wolff-Parkinson-White
syndrome, and two other patients with prior history of ar-
rhythmias developed perioperative arrhythmias requiring
treatment (Table 2). There were no perioperative events at-
tributable to myocardial ischemia alone. Death or cardiac
arrest occurred in three patients after liver transplantation
and was a consequence of severe intraoperative or postoper-
The present study of patients undergoing DSE for evalua-
tion for liver transplantation yielded several important ob-
servations. Notably, in this cohort of patients with careful
preoperative screening for cardiovascular disease, the overall
rate of serious cardiovascular complication rate was only
13%. Dobutamine stress echocardiography performed in
these patients with low to moderate risk of coronary disease
was often inconclusive because of inadequate heart rate re-
FIGURE 1. Illustration summarizing results
of DSE studies in patients undergoing eval-
uation for liver transplantation. See text
for details. Abbreviations: events ? cardio-
vascular events; WMA ? wall motion abnor-
TABLE 2. DSE findings and history of cardiovascular risks factors in patients with major events after
Patient No.Event DSE findings
Cardiac arrest (intraoperative
Cardiac arrest (postoperative splenic
artery aneurysm rupture)c
Age ?60 years
Age ?60 years
Age ?60 years
Age ?60 years
Age ?60 years
aAbbreviations: AVNRT?atrioventricular nodal reentrant tachycardia; post-op?postoperative; WPW?Wolf Parkinson White syndrome.
bPatient died three months later of sepsis and multisystem organ failure.
cSubsequent cardiac catheterization showed no evidence of coronary stenosis.
TABLE 1. Adverse effects during DSE in patients
undergoing liver transplantation evaluation
Adverse effects No. of patients (%)
Nausea and vomiting
WILLIAMS ET AL.
June 15, 2000
sponse, largely due to the use of ?-adrenergic blocking agents
for treatment of portal hypertension. Abnormal wall motion
during DSE was exceptionally rare and did not predict car-
diac events. On the other hand, normal wall motion during
DSE was not consistently associated with a favorable out-
Use of DSE in patients undergoing liver transplantation
has yielded conflicting results (4, 5). In a series of 71 patients
undergoing liver transplantation, similar to the findings of
the present report, Donovan et al. (4) found that ischemia
during dobutamine stress did not predict perioperative
events. However, a normal study—that is, the absence of
inducible myocardial ischemia—was useful in excluding
high-risk patients. In contrast, Plotkin et al. (5) found DSE
very efficacious in screening patients undergoing liver trans-
plantation. Importantly, patients in this study were selected
based on the presence of significant cardiac risk factors or
history of coronary artery disease; sensitivity and specificity
of DSE for coronary artery disease were 100%. The findings
of the present study contrast with this previous investigation
because of the striking difference in pretest likelihood of
The issues of safety and adverse effects during DSE are
particularly important in chronically ill patients undergoing
liver transplantation. Although no patient in the present
study experienced serious complications, such as complex
ventricular arrhythmia or death, 17% had significant ad-
verse effects during dobutamine infusion. These findings are
similar to observations in other groups of patients undergo-
ing DSE (7–10). The presence of intravascular volume deple-
tion due to cirrhosis and diuretic treatment might be ex-
pected to increase the risk of hypotension in these patients,
but severe reductions in blood pressure occurred in only 7%.
The major limitation of the present study relates to the
preselection of patients undergoing DSE. That is, patients
with known coronary artery disease or symptoms clearly
consistent with active myocardial ischemia were usually not
referred for DSE. Although this approach undoubtedly con-
tributed to the low prevalence of abnormal tests, it also
represents a reasonable clinical approach to preoperative
evaluation. A potential limitation relates to the detection of
cardiac events in the postoperative period. After transplan-
tation, patients were continuously monitored in the surgical
intensive care unit, but serial 12-lead electrocardiograms
and cardiac enzymes were not routinely obtained. It is pos-
sible that subclinical cardiac events were not detected. The
impact of subclinical events on outcome is unknown.
Dobutamine stress echocardiography can be safely per-
formed in most patients undergoing evaluation for liver
transplantation. Nonetheless, a variety of adverse effects are
observed, and studies are frequently nondiagnostic because
of inadequate heart rate response. Withdrawal of ?-adrener-
gic blockers for at least 24 hr prior to testing would be
expected to reduce the number of nondiagnostic studies. In
patients identified clinically as having low to moderate risk
for coronary artery disease, findings during DSE serve as a
poor predictor for major events after liver transplantation.
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Received 9 August 1999.
Accepted 2 December 1999.
Vol. 69, No. 11