Predictors of Cardiac Events After Major Vascular Surgery

Role of Clinical Characteristics, Dobutamine Echocardiography, and
beta-Blocker Therapy

Author Information <http://jama.ama-assn.org/issues/v285n14/rfull/#aainfo>
Eric Boersma, PhD; Don Poldermans, MD, PhD; Jeroen J. Bax, MD, PhD; Ewout W.
Steyerberg, MD, PhD; Ian R. Thomson, MD; Jan D. Banga, MD, PhD; Louis L. M.
van de Ven, MD, PhD; Hero van Urk, MD, PhD; Jos R. T. C. Roelandt, MD, PhD;
for the DECREASE Study Group
Context  Patients who undergo major vascular surgery are at increased risk
of perioperative cardiac complications. High-risk patients can be identified
by clinical factors and noninvasive cardiac testing, such as dobutamine
stress echocardiography (DSE); however, such noninvasive imaging techniques
carry significant disadvantages. A recent study found that perioperative
beta-blocker therapy reduces complication rates in high-risk individuals.
Objective  To examine the relationship of clinical characteristics, DSE
results, beta-blocker therapy, and cardiac events in patients undergoing
major vascular surgery.
Design and Setting  Cohort study conducted in 1996-1999 in the following 8
centers: Erasmus Medical Centre and Sint Clara Ziekenhuis, Rotterdam, Twee
Steden Ziekenhuis, Tilburg, Academisch Ziekenhuis Utrecht, Utrecht, and
Medisch Centrum Alkmaar, Alkmaar, the Netherlands; Ziekenhuis Middelheim,
Antwerp, Belgium; and San Gerardo Hospital, Monza, Istituto di Ricovero e
Cura a Carattere Scientifico, San Giovanni Rotondo, Italy.
Patients  A total of 1351 consecutive patients scheduled for major vascular
surgery; DSE was performed in 1097 patients (81%), and 360 (27%) received
beta-blocker therapy.
Main Outcome Measure  Cardiac death or nonfatal myocardial infarction within
30 days after surgery, compared by clinical characteristics, DSE results,
and beta-blocker use.
Results  Forty-five patients (3.3%) had perioperative cardiac death or
nonfatal myocardial infarction. In multivariable analysis, important
clinical determinants of adverse outcome were age 70 years or older; current
or prior angina pectoris; and prior myocardial infarction, heart failure, or
cerebrovascular accident. Eighty-three percent of patients had less than 3
clinical risk factors. Among this subgroup, patients receiving beta-blockers
had a lower risk of cardiac complications (0.8% [2/263]) than those not
receiving beta-blockers (2.3% [20/855]), and DSE had minimal additional
prognostic value. In patients with 3 or more risk factors (17%), DSE
provided additional prognostic information, for patients without
stress-induced ischemia had much lower risk of events than those with
stress-induced ischemia (among those receiving beta-blockers, 2.0% [1/50] vs
10.6% [5/47]). Moreover, patients with limited stress-induced ischemia (1-4
segments) experienced fewer cardiac events (2.8% [1/36]) than those with
more extensive ischemia (5 segments, 36% [4/11]).
Conclusion  The additional predictive value of DSE is limited in clinically
low-risk patients receiving beta-blockers. In clinical practice, DSE may be
avoided in a large number of patients who can proceed safely for surgery
without delay. In clinically intermediate- and high-risk patients receiving
beta-blockers, DSE may help identify those in whom surgery can still be
performed and those in whom cardiac revascularization should be considered.
JAMA. 2001;285:1865-1873



JOC10036
Patients with severe peripheral vascular disease frequently have underlying
coronary artery disease. Hence, patients undergoing major vascular surgery
are at increased risk for cardiac complications during or shortly after
surgery. Appropriate patient management then includes assessment of the
perioperative cardiac risk, as well as strategies to reduce this risk.
Several investigations demonstrated the utility of dobutamine stress
echocardiography (DSE) for preoperative cardiac risk assessment. 1-5
<http://jama.ama-assn.org/issues/v285n14/rfull/#r1>  Patients with
stress-induced new wall-motion abnormalities (NWMAs), a hallmark of
myocardial ischemia, are at an 8% to 38% risk of cardiac death or myocardial
infarction (MI) within 30 days after surgery. 2
<http://jama.ama-assn.org/issues/v285n14/rfull/#r2> , 4
<http://jama.ama-assn.org/issues/v285n14/rfull/#r4> , 6
<http://jama.ama-assn.org/issues/v285n14/rfull/#r6> , 7
<http://jama.ama-assn.org/issues/v285n14/rfull/#r7>  In contrast, patients
without NWMAs have much lower complication rates: in the range of 0% to 5%.
There are, however, significant disadvantages associated with the routine
use of DSE (or other noninvasive imaging techniques) in all vascular surgery
candidates. These include the substantial costs of the test, and, more
importantly, the risk of delaying surgery in patients with large aortic
aneurysms or critical limb ischemia. The recent Dutch Echocardiographic
Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) study
demonstrated that perioperative beta-adrenergic blockade with bisoprolol
reduces the risk of 30-day complications in patients with NWMAs to a risk
level as observed in patients without NWMAs. 8
<http://jama.ama-assn.org/issues/v285n14/rfull/#r8> , 9
<http://jama.ama-assn.org/issues/v285n14/rfull/#r9>  This finding raises the
question of whether DSE is indicated in all patients scheduled for vascular
surgery. Does simple perioperative administration of beta-blockers reduce or
eliminate the need for noninvasive preoperative cardiac testing? 10
<http://jama.ama-assn.org/issues/v285n14/rfull/#r10>  On the other hand, in
some patients the cardioprotective effect of beta-blockers may be
insufficient to effectively reduce perioperative cardiac events. These
patients may benefit from additional coronary revascularization. To address
these issues we studied the relationship between clinical characteristics,
DSE results, beta-blockers, and adverse cardiac outcome in a large series of
consecutive patients scheduled to undergo major vascular surgery.



METHODS



Patients

The study population consisted of 1351 consecutive patients scheduled for
elective major vascular surgery who were screened for eligibility for the
DECREASE study at 8 of the following participating centers: Erasmus Medical
Centre and Sint Clara Ziekenhuis, Rotterdam, Twee Steden Ziekenhuis,
Tilburg, Academisch Ziekenhuis Utrecht, Utrecht, and Medisch Centrum
Alkmaar, Alkmaar, the Netherlands; Ziekenhuis Middelheim, Antwerp, Belgium;
and San Gerardo Hospital, Monza, Istituto di Ricovero e Cura a Carattere
Scientifico, San Giovanni Rotondo, Italy. 8
<http://jama.ama-assn.org/issues/v285n14/rfull/#r8>  Per protocol, 846
patients with at least 1 of the following risk factors underwent DSE: age 70
years or older, angina, prior MI, congestive heart failure, treatment for
ventricular arrhythmias, treatment for diabetes mellitus, or limited
exercise capacity. Two hundred forty-five additional patients underwent DSE
at the discretion of the treating physician, based on other risk factors
(eg, hyperlipidemia and smoking). Thus, in total 1091 patients (81%)
underwent DSE. Perioperative beta-blockers were administered to 360 patients
(27%): 301 (22%) of the 1351 patients were treated long-term with
beta-blockers, and 59 (5%) were randomized to receive beta-blockers within
the framework of the DECREASE study. Eight patients who had extensive
resting and/or stress-induced ischemia were excluded from the DECREASE
study. Four of these underwent coronary artery bypass graft surgery, and 2
of them died during this operation. The 2 surviving patients subsequently
underwent uneventful vascular surgery with perioperative beta-blocker
administration for cardiac protection. The other 4 patients underwent
vascular surgery without prior myocardial revascularization and received
beta-blockers for cardiac protection. None of the other non-DECREASE
patients received beta-blockers for cardiac protection.
Dobutamine Stress Echocardiography

Dobutamine stress echocardiography was performed according to a standard
protocol. 11 <http://jama.ama-assn.org/issues/v285n14/rfull/#r11>  The left
ventricle was divided into 16 segments and wall motion was scored on a
5-point ordinal scale (1, normal wall motion; 2, mild hypokinesis; 3, severe
hypokinesis; 4, akinesis; and 5, dyskinesis). The results of DSE were
considered positive if new wall-motion abnormalities (NWMAs) occurred (ie,
if wall motion in any segment worsened by 1 more grades during the test,
with the exception of akinesis becoming dyskinesis). The extent and location
of ischemia were evaluated and a wall-motion index was calculated, both at
rest and during peak stress.
End Point Definition

The study end point was a composite of cardiac death or nonfatal MI (MI)
occurring during the period from screening until 30 days after surgery. An
adverse events committee adjudicated all end points. Deaths were considered
to be cardiac related unless there was explicit evidence for a noncardiac
cause. Myocardial infarction was defined by either a serum creatine kinase
level of more than 110 U/L with a myoglobin isoenzyme fraction of more than
10%, or by new Q waves faster than 30 milliseconds in duration on the
12-lead electrocardiogram.
Data Analysis

Univariable and multivariable logistic regression analyses were applied to
evaluate the relations between a limited number of baseline clinical
characteristics, DSE results, beta-blocker therapy, and the composite end
points as outlined above. All variables that reached a P value <.50 in
univariable analysis entered the multivariable stage. Multivariable models
were constructed by backward deletion of the least significant
characteristics, applying the Akaike optimal information criterion. 12
<http://jama.ama-assn.org/issues/v285n14/rfull/#r12> , 13
<http://jama.ama-assn.org/issues/v285n14/rfull/#r13>  Special attention was
paid to the extent to which DSE results and beta-blocker therapy contributed
to the prognostic information obtained from clinical characteristics alone.
Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) are
reported.
Despite the fact that the population consisted of patients undergoing
high-risk surgery, the number of outcome events appeared to be limited.
Therefore, there was a serious concern that model overfitting would occur.
To overcome this, we limited the number of candidate clinical variables to
be included in the model, whereby, particularly, the results of prior risk
modeling analyses in surgical patients were considered. 14-17
<http://jama.ama-assn.org/issues/v285n14/rfull/#r14>  Furthermore, we
applied a clinical risk model that was developed elsewhere to our data set,
and collapsed the clinical risk assessment into 1 index variable.
Subsequently, the prognostic value of this risk index and the additional and
additive prognostic value of DSE results and beta-blocker therapy were
analyzed by logistic regression analyses. We chose the risk index that was
recently developed by Lee and colleagues 17
<http://jama.ama-assn.org/issues/v285n14/rfull/#r17>  in a data set of 4315
patients undergoing major noncardiac surgery, including 898 patients
undergoing vascular surgery. To compose the Lee risk index, 1 point is
assigned to each of the following characteristics: high-risk type of
surgery, known ischemic heart disease, a history of congestive heart
failure, a history of cerebrovascular disease, diabetes mellitus, and renal
failure.
The performance of the risk models was determined by the cardiac index,
which indicates how well a model rank-orders patients with respect to their
outcomes; the cardiac index ranges from 0.5 (not predictive at all) to 1.0
(optimal performance). 18
<http://jama.ama-assn.org/issues/v285n14/rfull/#r18>  In addition, the
Hosmer-Lemeshow statistic for goodness of fit is presented. The predictive
accuracy of the models was further evaluated by bootstrapping techniques. 19
<http://jama.ama-assn.org/issues/v285n14/rfull/#r19>  One hundred bootstrap
samples were drawn from the original data set (with replacement) and the
full modeling process, including the stepwise selection, was redone in every
bootstrap sample. The models developed in the bootstrap samples were
subsequently tested in the original data set. This process provides a factor
to correct for a possible overoptimism of the cardiac index. 20
<http://jama.ama-assn.org/issues/v285n14/rfull/#r20>
Based on the results obtained by the described modeling strategies, a risk
score was developed to estimate an individual patient's risk of
perioperative cardiac death or MI. Furthermore, a simple decision-tree is
constructed to help the physician decide in which patients to refer for
noninvasive perioperative cardiac testing.



RESULTS



The primary patient characteristics are described in Table 1
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_t1.html> .
Obviously, patients receiving beta-blockers during surgery had a risk
profile that was worse than that of patients not taking such medication
because they had higher rate of hypertension, ventricular arrhythmias, and
history of coronary disease. Furthermore, patients receiving beta-blockers
more frequently used other cardiac medications than those who were not
receiving beta-blockers. There were 45 perioperative cardiac complications
(3.3%): 31 patients had cardiac death and another 14 nonfatal MI.
Univariable Models

In univariable analysis, a history of heart failure was the most significant
determinant of adverse cardiac outcome among the clinical variables examined
( Table 2
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_t2.html> ). The
subgroup of patients with a history of heart failure (5% of the population)
had a more than 5-fold increase in the risk of perioperative cardiac death
or MI compared with those without such a history. Other important
univariable determinants of perioperative cardiac complications were a
history of MI, prior cerebrovascular accident (CVA), current or prior angina
pectoris, and age 70 years and older. Patients taking cardiac medications
had higher event rates than patients not taking such medication; statistical
significance was observed for nitrates and angiotensin-converting enzyme
(ACE) inhibitors. There was no relationship between the type of surgery and
the composite end point.
Patients who did not undergo DSE (ie, patients without clinical cardiac risk
factors) and those without NWMAs during DSE had a significantly lower
cardiac death or MI rate than patients with NWMAs during DSE (0.4% and 1.6%
vs 13.5%, respectively (P<.001; Table 3
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_t3.html> ). Thus,
NWMAs were strongly predictive of adverse perioperative cardiac outcome.
Moreover, the extent of stress-induced ischemia also provided important
prognostic information, as the event rates ranged from 10.8% in those with
NWMAs in 1 to 4 segments to 23.9% in patients with NWMAs in 5 or more
segments. The echocardiogram at rest also provided prognostic information.
Patients with 5 or more abnormal segments had a 4- to 6-fold increased risk
of cardiac complications compared with those with a normal or slightly
aberrant (1-4 abnormal segments) wall motion at rest.
Despite their overall risk profile being worse ( Table 1
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_t1.html> ),
patients receiving beta-blockers during surgery had a significantly reduced
risk of cardiac death or MI compared with those not taking such medication.
Among the 254 patients who did not undergo DSE, no perioperative cardiac
complications were observed in the 8.7% of patients receiving beta-blockers,
whereas there was 1 event (0.4%) in the remaining patients. In the 875
patients without stress-induced NWMAs, 22% were receiving beta-blockers. One
cardiac complication (0.5%) occurred in this group, and there were 13 (1.9%)
in those not receiving beta-blockers. Finally, in the 222 patients with
NWMAs, 67% of those receiving beta-blockers with 4.7% having a perioperative
cardiac event vs 31.5% among those not receiving beta-blockers. There was no
evidence of a differential effect of beta-blocker therapy in these patient
categories (homogeneity test for ORs, P = .69), so that the crude OR is best
estimated by the method of Mantel-Haenszel test (0.1; 95% CI, 0.1-0.3).
Multivariable Models

Many of the univariably significant clinical determinants of cardiac outcome
remained important in the multivariable analysis ( Table 4
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_t4.html> ). After
correcting for other determinants, prior CVA showed the strongest
relationship with perioperative cardiac complications. A history of heart
failure and prior MI were the next strongest clinical predictors. Angina and
age 70 years or more were also important. After correcting for differences
in clinical characteristics, patients receiving beta-blockers were still at
significantly lower risk for the composite end point than those who were not
(adjusted OR, 0.3; 95% CI, 0.1-0.7).
When clinical data were combined with DSE results, advanced age, angina
pectoris, prior MI, and prior heart failure lost most of their predictive
power with respect to the composite end point. In fact, DSE results
(especially the presence or absence of NWMAs) were the most important
determinants of perioperative cardiac outcome. In connection with both
clinical data and DSE results, beta-blocker therapy was again associated
with a significantly reduced risk of the composite end point. The protective
effect of beta-blocker therapy was observed in long-term users (OR, 0.1; 95%
CI, 0.0-0.3) as well as in patients who received bisoprolol as part of the
DECREASE study (OR, 0.1; 95% CI, 0.0-0.4).
Application of the Lee Risk Index

In all, 611 patients (45%) had a Lee risk index of 1, 509 (38%) had an index
of 2, and 231 (17%) had an index of 3 or more points (note that all patients
underwent high-risk surgery, and thus had a risk index 1 points). The
incidence of the composite end point in these patients was 1.3%, 3.1%, and
9.1% (P<.001). Regression analysis revealed a crude OR of 2.3 for the
composite end point associated with a 1-point increase in the risk index
(95% CI, 1.8-3.1). Multivariable analyses again demonstrated the additional
and additive prognostic value of DSE results and beta-blocker therapy
 Table 5
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_t5.html> ).
Predictive Accuracy

The cardiac index for the composite end point model based on clinical
characteristics only was 0.78, reflecting good ability to discriminate
between patients who did and did not have a life-threatening cardiac
complication. The associated goodness of fit of the chi27 statistic was 2.1
(P = .95). After correction for overoptimism the cardiac index was 0.72,
still reflecting satisfactory performance. The multivariable model that
combined clinical data with DSE results had considerably better
discriminating power with a cardiac index of 0.87 (goodness of fit chi26 =
7.6, P = .27; optimism-corrected cardiac index, 0.82). The cardiac index
connected with the Lee risk-index-alone model was 0.71 (goodness of fit
chi26, 7.0; P = .32) and improved to 0.87 by adding DSE results and
information regarding beta-blocker therapy.
Risk Classification Model

Based on the results described above, a simple scheme was developed to
estimate a patient's risk of perioperative cardiac complications ( Figure 1
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_f1.html> ). A
clinical risk score can be determined on the basis of the patient's age and
clinical history. If this risk score is in the range of 0 to 2 points (83%
of the patients belonged to this category) and the beta-blockers are
administered perioperatively, the estimated cardiac complication rate is
relatively low (<2%), irrespective of the DSE result. The estimated risk of
cardiac complications is also low in patients with a risk score of 3 or more
points without NWMAs, provided beta-blockers will be applied. Patients with
a risk score of 3 or more and NWMAs were at a considerable cardiac risk
(>6%), despite beta-blocker therapy.



COMMENT



Consistent with other studies, 14-17
<http://jama.ama-assn.org/issues/v285n14/rfull/#r14>  our analysis of 1351
patients undergoing high-risk noncardiac vascular surgery demonstrated that
advanced age, current or prior angina, and a history of cardiac or cerebral
events are the most important clinical determinants of perioperative cardiac
death or MI. Apart from clinical data, DSE results were highly predictive of
adverse cardiac outcome, which also confirms other investigations. 1
<http://jama.ama-assn.org/issues/v285n14/rfull/#r1>  Patients receiving
beta-blockers had significantly lower risk than those not receiving them. It
should be emphasized that patients receiving beta-blockers had a
considerably worse overall risk profile than those not receiving them, which
makes this result even more convincing. The additional and additive
prognostic value of DSE results and beta-blocker therapy was confirmed in
the analysis that applied the previously developed Lee risk index. On the
basis of a risk score composed of a weighted sum of the prognostic clinical
characteristics, a large group (83%) of low-risk patients with a score of
less than 3 could be defined. In this group, the estimated risk of cardiac
complications is less than 1%, regardless of DSE results, as long as
patients are receiving beta-blockers. In the remaining patients, those
without stress-induced ischemia also had a low estimated cardiac risk in the
presence of perioperative beta-blocker therapy.
Univariable analyses showed that patients with diabetes mellitus, pulmonary
disease, prior ventricular arrhythmias, or aortic valvular stenosis are at
increased risk of surgical complications. However, in contrast to earlier
studies, 16 <http://jama.ama-assn.org/issues/v285n14/rfull/#r16> , 21
<http://jama.ama-assn.org/issues/v285n14/rfull/#r21>  these factors were not
independent predictors in our multivariable analyses. This finding can be
reflect a changing patient population or improved perioperative management
although it may also be a matter of (lack of) power. Additionally, it should
be emphasized that cardiac death or MI during complex surgery is most likely
to occur in patients with stress-inducible cardiac ischemia. Indeed, the
occurrence of NWMAs during DSE was a major determinant of adverse outcome.
Because a stress-induced ischemia was not more common in patients with
diabetes mellitus, pulmonary disease, prior ventricular arrhythmias, or
aortic stenosis (78 NWMAs of 352 cases [22%]) than in patients without such
characteristic (144 NWMAs of 745 cases [19%]; P = .28), these
characteristics are likely not strong determinants of a predisposition to
ischemia. In contrast, patients with prior MI, prior heart failure, or prior
CVA were more likely to have stress-induced ischemia than other patients
(150 NWMAs of 545 cases [28%] vs 72 NWMAs of 552 cases [13%]; P<.001).
Still, factors such as diabetes mellitus, may be predictive of long-term
complications. Diabetes mellitus (and renal failure) were therefore still
incorporated in the clinical risk index ( Figure 1
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_f1.html> ).
Clinical Implications

Figure 2 <http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_f2.html>
may help to understand how results can be translated into clinical practice.
The perioperative cardiac event rate was low (1%) in patients with a
clinical risk score of less than 3 points and who were receiving
beta-blockers. It seems therefore appropriate to omit DSE (and other
noninvasive cardiac testing) in this large (>80%) group of patients and to
proceed expeditiously with surgery under protection by beta-blocker therapy.
Dobutamine stress echocardiography is useful to further risk-stratify
patients with a clinical risk score of 3 or more points. If protected by
perioperative beta-blockade, patients without stress-induced ischemia still
had a low complication rate (2%) and are also candidates for prompt surgery.
Patients with a risk score of 3 or more points and NWMAs (approximately 6%
of the population) had a considerable complication rate despite the
beta-blocker therapy. Our data suggest that the proposed treatment policy in
these patients may depend on the extent of stress-induced ischemia. Although
the numbers of patients and events are relatively small in the specific
subgroups, patients with NWMAs in 1 to 4 segments were properly protected by
beta-blockers. In patients with more extensive ischemia, however,
beta-blockers failed to reduce the rate of perioperative cardiac
complications. Cardiac catheterization and subsequent myocardial
revascularization should be considered in these patients.
The prescription of beta-blockers may delay surgery; so far, no study has
indicated what the optimal run-in period of this drug is in this setting.
Therefore, it can be questioned whether such therapy is really necessary in
patients at very low risk. In the group of patients with a risk score of 0
points, 1.2% perioperative complications were observed in those without
beta-blocker therapy ( Figure 2
<http://jama.ama-assn.org/issues/v285n14/fig_tab/joc10036_f2.html> ). This
complication rate seems sufficiently low to refrain from administering
medication indeed and opt for surgery without delay. Another issue is that
beta-blocker therapy may be contraindicated, especially in patients with
reactive airway diseases, such as severe asthma or chronic obstructive
pulmonary disease with a reactive component. It should be noticed that these
patients are rare: there were no such cases in our data set. Still, if
beta-blocker therapy is contraindicated, the use of calcium antagonists with
a negative chronotropic effect may be considered. The recent Incomplete
Infarction Trial of European Research Collaborators Evaluating Prognosis
post-Thrombolysis (INTERCEPT) study of post-MI patients reported fewer
cardiac events in patients randomized to such a drug compared with placebo.
22 <http://jama.ama-assn.org/issues/v285n14/rfull/#r22>
Study Limitations

Because of its retrospective nature, our analysis has limitations, which
should be considered when interpreting the results. The risk-stratification
and modification scheme using a clinical risk score, DSE, and beta-blocker
therapy was developed after events had occurred. Furthermore, only some
patients (those participating in the DECREASE study) were randomized to
receive either perioperative beta-blockers or standard care. Patient
characteristics may have played an important role in the decision to
administer beta-blockers to patients who did not participate in the DECREASE
study and could potentially bias the results. Importantly, we found no
difference in the cardioprotective effect of beta-blockers between patients
who were randomized within the framework of the DECREASE study and those
whose receipt of beta-blockers was chronic. This suggests that the utility
of perioperative beta-adrenergic blockade extends beyond the small subset of
high-risk patients who participated in the DECREASE study. Finally, the
observed event rates were relatively low compared with previous
investigations. It should be appreciated that our results were obtained in
selected, high-volume hospitals (3 of the participating hospitals were
university hospitals) and that cardiac event rates might differ in other
centers.
Conclusions

Dobutamine stress echocardiography effectively identifies patients at risk
for perioperative cardiac events. Besides, our data showed that the
additional predictive value of DSE is limited in clinically low-risk
patients receiving beta-blockers. This observation may have important
clinical implications: in a majority of patients, additional testing by DSE
can be avoided and patients can proceed safely for surgery without delay. In
a smaller group of clinically intermediate- and high-risk patients, DSE may
help to identify patients in whom surgery can still be performed while
receiving beta-blockers and those in whom cardiac revascularization should
be considered.



Author/Article Information


Author Affiliations: University Hospital Rotterdam, Rotterdam (Drs Boersma,
Poldermans, Steyerberg, van de Ven, van Urk, and Roelandt), the University
Hospital Leiden, Leiden (Dr Bax), and University Hospital Utrecht, Utrecht
(Dr Banga), the Netherlands; and University of Manitoba, Winnipeg (Dr
Thomson).

Corresponding Author and Reprints: Don Poldermans, MD, PhD, University
Hospital Rotterdam, Department of Surgery, Room H921, Dr Molewaterplein 40,
3015 GD Rotterdam, the Netherlands (e-mail: [log in to unmask]
<mailto:[log in to unmask]> ).
Author Contributions: Study concept and design: Boersma, Poldermans,
Roelandt.
Acquisition of data: Boersma, Poldermans.
Analysis and interpretation of data: Boersma, Poldermans, Bax, Steyerberg,
Thomson, Banga, van de Ven, van Urk.
Drafting of the manuscript: Boersma, Poldermans.
Critical revision of the manuscript for important intellectual content: Bax,
Thomson, Banga, van de Ven, van Urk, Roelandt.
Statistical expertise: Boersma, Steyerberg.
Study supervision: Roelandt.
Members of the Dutch Echocardiographic Cardiac Risk Evaluation Applying
Stress Echocardiography group are listed in Poldermans D, Boersma E, Bax JJ,
et al, for the Dutch Echocardiographic Cardiac Risk Evaluation Applying
Stress Echocardiography Study Group. The effect of bisoprolol on
perioperative mortality and myocardial infarction in high-risk patients
undergoing vascular surgery. N Engl J Med. 1999;341:1789-1794.




REFERENCES



1. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr1>
Poldermans D, Fioretti PM, Forster T, et al.
Dobutamine stress echocardiography for assessment of perioperative cardiac
risk in patients undergoing major vascular surgery.
Circulation.
1993;87:1506-1512.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8491005>
2. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr2>
Poldermans D, Arnese M, Fioretti PM, et al.
Improved cardiac risk stratification in major vascular surgery with
dobutamine-atropine stress echocardiography.
J Am Coll Cardiol.
1995;26:648-653.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7642854>
3. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr3>
Pellikka PA, Roger VL, Oh JK, Seward JB, Tajik AJ.
Safety of performing dobutamine stress echocardiography in patients with
abdominal aortic aneurysm > or = 4 cm in diameter.
Am J Cardiol.
1996;77:413-416.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8602573>
4. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr4>
Davila-Roman VG, Waggoner AD, Sicard GA, Geltman EM, Schechtman KB, Perez
JE.
Dobutamine stress echocardiography predicts surgical outcome in patients
with an aortic aneurysm and peripheral vascular disease.
J Am Coll Cardiol.
1993;21:957-963.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8450165>
5. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr5>
Poldermans D, Bax JJ, Thomson IR, et al.
Role of dobutamine stress echocardiography for preoperative cardiac risk
assessment before major vascular surgery.
Echocardiography.
2000;17:79-91.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10978964>
6. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr6>
Lalka SG, Sawada SG, Dalsing MC, et al.
Dobutamine stress echocardiography as a predictor of cardiac events
associated with aortic surgery.
J Vasc Surg.
1992;15:831-840.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1578539>
7. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr7>
Langan EM, Youkey JR, Franklin DP, Elmore JR, Costello JM, Nassef LA.
Dobutamine stress echocardiography for cardiac risk assessment before aortic
surgery.
J Vasc Surg.
1993;18:905-911.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8264046>
8. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr8>
Poldermans D, Boersma E, Bax JJ, et al.
The effect of bisoprolol on perioperative mortality and myocardial
infarction in high-risk patients undergoing vascular surgery.
N Engl J Med.
1999;341:1789-1794.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10588963>
9. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr9>
Lee TH.
Reducing risk in noncardiac surgery.
N Engl J Med.
1999;341:1838-1840.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10588971>
10. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr10>
Mayet J, Wolfe J, Foale R.
Cardiac risk stratification [letter].
Lancet.
2000;355:500.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10841160>
11. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr11>
McNeill AJ, Fioretti PM, el-Said SM, Salustri A, Forster T, Roelandt JR.
Enhanced sensitivity for detection of coronary artery disease by addition of
atropine to dobutamine stress echocardiography.
Am J Cardiol.
1992;70:41-46.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
1615868>
12. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr12>
Akaike H.
Information theory as an extension of the maximum likelihood principle.
In: Petrov BN, Csaki F, eds. Second International Symposium on Information
Theory. Budapest, Hungary: Akademia Kiado; 1973:267-281.
13. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr13>
Boersma E, Pieper KS, Steyerberg EW, et al.
Predictors of outcome in patients with acute coronary syndromes without
persistent ST-segment elevation: results from an international trial of 9461
patients.
Circulation.
2000;101:2557-2567.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10840005>
14. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr14>
Mangano DT, Goldman L.
Preoperative assessment of patients with known or suspected coronary
disease.
N Engl J Med.
1995;333:1750-1756.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
7491140>
15. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr15>
Eagle KA, Brundage BH, Chaitman BR, et al, for the Committee on
Perioperative Cardiovascular Evaluation for Noncardiac Surgery.
Guidelines for perioperative cardiovascular evaluation for noncardiac
surgery: Report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines.
Circulation.
1996;93:1278-1317.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8653858>
16. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr16>
L'Italien GJ, Paul SD, Hendel RC, et al.
Development and validation of a Bayesian model for perioperative cardiac
risk assessment in a cohort of 1,081 vascular surgical candidates.
J Am Coll Cardiol.
1996;27:779-786.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
8613603>
17. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr17>
Lee TH, Marcantonio ER, Mangione CM, et al.
Derivation and prospective validation of a simple index for prediction of
cardiac risk of major noncardiac surgery.
Circulation.
1999;100:1043-1049.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10477528>
18. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr18>
Kendal DG.
Rank Correlation Methods.
London, England: Charles Griffin; 1962.
19. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr19>
Gong G.
Cross-validation, the jackknife, and the bootstrap: excess error estimation
in forward logistic regression.
J Am Stat Assoc.
1986;81:108-113.
20. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr20>
Van Houwelingen JC, Le Cessie S.
Predictive value of statistical models.
Stat Med.
1990;9:1303-1325.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2277880>
21. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr21>
Mangano DT.
Perioperative cardiac morbidity.
Anesthesiology.
1990;72:153-184.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
2404426>
22. <http://jama.ama-assn.org/issues/v285n14/rfull/#rr22>
Boden WE, van Gilst WH, Scheldewaert RG, et al, for the Incomplete
Infarction Trial of European Research Collaborators Evaluating Prognosis
post-Thrombolysis (INTERCEPT).
Diltiazem in acute myocardial infarction treated with thrombolytic agents: a
randomised placebo-controlled trial.
Lancet.
2000;355:1751-1756.
MEDLINE
<http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=
10832825>



Edward E. Rylander, M.D.
D.A.B.F.P and D.A.B.P.M.