(Circulation. 1999;100:924-932.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Prognostication in 3-Vessel Coronary Artery Disease Based on Left Ventricular Ejection Fraction During Exercise
Influence of Coronary Artery Bypass Grafting
From the Division of Cardiovascular Pathophysiology, The Joan and Sanford I. Weill Medical College of Cornell University, The New York Presbyterian Hospital–Weill Cornell Medical Center, New York, NY.
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Abstract |
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Background—Previous data indicate that left ventricular ejection fraction (LVEF) provides prognostic information among patients with coronary artery disease (CAD), but the value of such testing specifically for defining benefits of coronary artery bypass grafting (CABG) may relate to severity of exercise-inducible ischemia measured noninvasively before surgery.
Methods and Results—To determine the independent prognostic
importance of preoperative ischemia severity for predicting
outcomes of CABG among patients with extensive CAD, we monitored 167
stable patients with angiographically documented 3-vessel CAD (average
follow-up of 9 years in event-free patients) who previously had
undergone rest and exercise radionuclide cineangiography. Their course
was correlated with data obtained during initial radionuclide testing,
coronary arteriography, and clinical evaluation at study entry.
Fifty-two patients received medical treatment only, and 115 underwent
CABG (44 early [
1 month after initial study]).
Multivariate Cox model analysis indicated that
change (
) in LVEF from rest to exercise during radionuclide study
was the strongest independent predictor of major cardiac events
(P=0.003) before surgery and also predicted magnitude of
CABG benefit (P=0.04). Patients with LVEF -8% or
less derived significant survival-prolonging and event-reducing benefit
from CABG performed 1 month after initial testing
(P<0.02 for cardiac death and P=0.008
for cardiac events], early CABG versus medical-treatment-only
patients); similar benefits were absent among patients with LVEF
more than -8%, and among those in whom CABG was deferred.
Conclusions—Assessment of ischemia severity based on LVEF response to exercise enables effective prognostication among patients with 3-vessel CAD and defines the likelihood of life-prolonging and event-reducing benefits from CABG.
Key Words: prognosis • ischemia • coronary disease • grafting
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Introduction |
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Left ventricular ejection fraction (LVEF) during exercise provides prognostic information among clinically stable patients with coronary artery disease (CAD).1 2 3 4 5 However, few studies have assessed the predictive value of exercise LVEF among patients with disease specifically involving all 3 major coronary systems,1 3 6 7 8 and none has examined the independent prognostic value of change (
) in LVEF with exercise
in this population. Moreover, the relative effects of CABG and of
nonsurgical therapy on long-term outcome among subpopulations with
equivalent pretherapy LVEF exercise responses are poorly understood,
precluding optimal application of test results in patient management.
Finally, no publication has examined the prognostic implications of
early versus delayed surgery or the interaction between
ischemia severity and the time between ischemia
assessment and CABG. Elucidation of these relationships is important. Trials of CABG performed without reference to pretherapy exercise left ventricular (LV) performance or timing of surgery disagree regarding benefits of surgery among patients with 3-vessel disease,9 10 11 although several investigations9 12 13 14 suggest greater life prolongation from surgery if any exercise-inducible ischemia is present before operation than in its absence. LVEF during exercise, as measured by echocardiograms,15 myocardial perfusion scintigrams when 99mTc-labeled radionuclides16 are used, or radionuclide cineangiograms,17 increasingly is used in the management of patients with CAD. Therefore, prognostic precision is needed from such testing to optimize management and to reduce healthcare expenditures.
Accordingly, we analyzed data from a cohort of 167 clinically
stable patients who between 1979 and 1983 were entered in a
prospectively designed, long-term follow-up study. At study entry,
these patients had angiographically confirmed 3-vessel CAD and
underwent rest and exercise radionuclide cineangiography for
determination of ischemia severity by LVEF analysis.
Our objectives were to determine cardiac mortality and event reduction
from CABG compared with medical therapy among patients with similar LV
performance characteristics at study entry and to determine
whether the impact of CABG is influenced by the magnitude of
preoperative ischemia severity or the interval between the
definition of ischemia and surgery. In addition, we sought to
define the relative prognostic value of LVEF, other exercise and
radionuclide-based findings, selected clinical risk descriptors, and
coronary angiographic characteristics during nonsurgical
follow-up.
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Methods |
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Patient Population
The study population was drawn from 324 consecutive patients with angiographically confirmed 3-vessel CAD (without associated left main coronary artery stenosis) who underwent maximal, symptom-limited exercise radionuclide cineangiography at The New York Hospital between August 1979 and August 1983 within 1 year of cardiac catheterization and who had no known myocardial infarction (MI) between catheterization and radionuclide study. Patients were excluded if they had prior CABG (51 patients), unstable angina or MI
30 days before radionuclide study
(64 patients), hemodynamically important primary
valvular heart disease (7 patients),
cardiomyopathy (2 patients), or left bundle-branch
block (1 patient). In addition, patients were excluded if LVEF at rest
was <30% at initial study (32 patients); this characteristic confers
major independent risk for adverse cardiac outcomes,18 19 20
potentially confounding results in the less dysfunctional majority.
After these exclusions, 167 patients remained and were allocated into
several subgroups. Of the 167 patients, 52 remained free from CABG
throughout their entire follow-up. This cohort ("medical-treatment
only") served as the control group for comparison with the remaining
115 patients, all of whom underwent CABG, 105 without and 10 after
intercurrent MI. Patients who underwent surgery were analyzed
as a group and also were divided into early (CABG 1 month, mean
2.5±8.9 days after initial radionuclide cineangiogram;
n=44 patients) and late (CABG >1 month after initial study, mean
interval 14.5±22.9 months; n=71 patients) subgroups for
analysis of the effect of CABG delay. The clinical course of
all 115 CABG patients and of the early and late CABG subgroups were
contrasted independently with the experience of the 52
medical-treatment-only patients. In addition, the prognostic
implications of LV performance were assessed in a group
combining the 52 medical-treatment-only patients with the 47 others who
underwent late CABG but had not yet had surgery >3 months after
initial study or reached a study end point before CABG. The latter
grouping ("expanded medical treatment") enabled confirmation of
results from the smaller medical-treatment-only group and increased
statistical power for evaluation of relative prognostic efficiency of
different descriptors during nonsurgical follow-up. As in earlier
studies,3 21 22 3 months was selected as the minimum
initial period of medical therapy after radionuclide testing.
Procedures
Radionuclide Cineangiography
Gated equilibrium radionuclide cineangiography was performed
according to our standard procedures, at rest and during
symptom-limited supine bicycle exercise, after intravenous
administration of 10 to 30 mCi of
99mTc.23 24 Exercise studies were
initiated at 25 W; load was generally increased by 25-W increments
every 2 minutes until angina, dyspnea, or exercise-limiting fatigue
occurred. Heart rate and rhythm were monitored continuously during
exercise; blood pressure was recorded at 
2-minute intervals.
Coronary Arteriography
Selective arteriography was performed in all patients as part of
their clinically mandated evaluation. Lesions were considered
hemodynamically important when they caused 
50%
reduction of coronary luminal diameter. Lesions were classified
as proximal if they were proximal to the first septal perforator in the
left anterior descending artery (LAD), proximal to the first obtuse
marginal branch in the circumflex artery, or in the proximal half of
the right coronary artery in the AV groove. Gensini
scores25 were calculated to index lesion severity,
location of lesions, and adequacy of collateral circulation.
Clinical Characteristics
Baseline data included age at radionuclide study, sex, history
of MI, chronic use of antianginal medications, and history of
hypertension and diabetes. Severity of angina was graded according to
New York Heart Association (NYHA) criteria.26
Coronary Artery Bypass Grafting
Patients underwent CABG at various intervals after radionuclide
study. During the period when most operations were performed (1979 to
1983), standard procedure at our institution involved hemodilution
prime and moderate systemic hypothermia, with cold cardioplegic
arrest for myocardial preservation during the period of cross-clamping.
Most CABG patients (86%) received between 2 and 4 grafts. The great
majority were saphenous veins; internal mammary artery grafts were used
in 3% of patients. Adequacy of revascularization
was indexed to the number of graft anastomoses divided by the number of
major vessels/branches with hemodynamically important
lesions.27
Follow-Up
Clinical course was assessed by periodic telephone interview or
questionnaire mailed to the patient, family member, or patient's
physician, supplemented by medical chart review (protocol approved by
Cornell University Medical College). During each follow-up, vital
status and occurrence of nonfatal cardiac events, hospitalizations, and
cardiac revascularization (CABG or PTCA) were
recorded. Nonfatal MI was inferred from clinical history,
corroborated whenever possible (82% of patients) by ECG, enzyme
evidence, or physician report. The decision to undertake CABG was made
by the patients and their physicians and was not dictated by research
protocol. Patients lost to follow-up were tracked via the Pension
Benefit Information Research Services or the National Death Index at
the National Center for Health Statistics. Death certificates were
obtained whenever possible from state departments of health. Cause of
death was determined from death certificates, chart review, or contact
with the decedent's family and/or physician. Deaths were considered
cardiac if they occurred proximate to MI, were due to congestive heart
failure, or were known to have been sudden or if cause could not be
defined. Mean follow-up of event-free patients was 8.9±2.0 (range 2.2
to 13.6) years. Of the 167 patients in the study population, 162
(97%) were followed up to death, MI, or 5 event-free years. The
status of 32 patients who had not undergone surgery was not precisely
known on January 1, 1994, after which no additional data were entered;
all but 3 of these had been followed up for 8 years.
Statistical Analysis
Baseline differences (continuous variables) among the early
CABG, late CABG, and medical-treatment-only subgroups were examined by
1-way ANOVA followed by Tukey's studentized range test when
ANOVA indicated significant global intergroup variation; ordinal and
categorical baseline variables were compared by the Kruskal-Wallis
or 
2 tests. Survival curves were constructed
by the Kaplan-Meier product-limit estimate method28
and compared by the log-rank test (Mantel Cox)29 to
contrast the clinical course of non-CABG (medical-treatment-only) and
CABG patients. Events considered in these analyses included
cardiac deaths alone and major cardiac events (deaths and nonfatal MI),
including those perioperative to CABG. When applicable,
patient experience was censored at the time of preoperative MI, repeat
CABG, PTCA, or documented noncardiac death. To examine the effect of
preoperative MI and permit statistical evaluation of the postoperative
course of all patients, a secondary analysis disregarded
preoperative events among patients with intercurrent MIs. Separate
comparisons were conducted for subgroups categorized according to time
of operation (early versus late) and relative ischemia severity
at baseline. We used the Cox proportional hazards model30
to evaluate differences in the relative hazard of major cardiac events
among the medical-treatment-only versus CABG subgroups by stratifying
the population according to 3 ranges of baseline ischemia
severity, defined as 10% increments in LVEF (ie, twice the
published standard error of the LVEF determination31 )
around our median LVEF value. Finally, log-rank test
comparison of Kaplan-Meier survival curves was performed to screen
baseline variables for their univariate relation to
initial cardiac event (death or nonfatal MI) in the
expanded-medical-treatment subgroup; again, censoring occurred at
documented noncardiac deaths and
revascularizations. Variables screened are
listed in Tables 1
and 2; data were not included in primary
analysis unless evaluable in 90% of the population. For
univariate screening, LVEF was partitioned at its
statistical median and again at 0; univariate survival
analysis also was performed post hoc on the subset of patients
with relatively severe (70% luminal diameter narrowing)
stenoses to determine whether LVEF provided prognostic
information beyond that given by coronary anatomy
alone. Other continuous variables were partitioned either according
to previously validated prognostic cutpoints or, when cutpoints had not
been defined previously, according to their statistical medians or in
tertiles, as appropriate. Variables found to be statistically
significant or that manifested a trend toward significance in
univariate analysis were entered into a forward
stepwise multivariate Cox regression model to examine
their independent value in predicting cardiac risk. Variables
entered into the Cox model were partitioned according to the same
cutpoints used for univariate analyses to render
hazards approximately proportional across strata. To equalize risk
exposure among groups, all time-dependent analyses were indexed
to the date of initial radionuclide study. The criterion for
statistical significance was P<0.05.
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Results |
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Baseline Characteristics
Clinical and Arteriographic Variables
Most patients had angina (NYHA functional class II or III); the majority reported long-term use of antianginal medications (Table 1
) for some period before testing. Approximately half the
patients had a history of MI before initial study. Fewer had
hypertension; diabetes was relatively uncommon. Proximal involvement of
all major vessels was present in relatively few patients; half had
significant LAD involvement. Among CABG patients, 75% of
hemodynamically important lesions were bypassed.
Baseline clinical and coronary anatomic characteristics of the
52 medical-treatment-only patients were similar to those of the 44
early and 71 late CABG patients, except that average Gensini score was
higher among CABG patients than among medical-treatment-only patients
(P<0.005), whereas angina severity was higher among early
CABG than among medical-treatment-only patients (P<0.05).
Both adequacy of revascularization and use of
internal mammary artery grafts were similar in early and late CABG
patients.
LVEF, Blood Pressure, Heart Rate, and Exercise Tolerance
LVEF at rest reached or exceeded the lower limit of normal in most
(60%) of the patients. LVEF increased with exercise in 12% of the
patients. Among those in whom LVEF failed to rise, a fall of 8%
(ejection fraction units) with exercise occurred in the majority. This
value, -8%, was the statistical median of the distribution of LVEF
in the expanded-medical-treatment subgroup. Despite equivalent exercise
duration and load during initial testing, baseline LVEF fell further
(P<0.001) during exercise among patients who subsequently
underwent either early or late CABG than among those who never
underwent surgery. Other baseline differences included lower average
peak exercise systolic blood pressure and exercise heart
rate–blood pressure double product (P<0.005 for both
variables) and smaller average changes from rest to exercise in
systolic blood pressure (P<0.005) and heart
rate–blood pressure double products (P<0.05),
primarily among early CABG versus medical-treatment-only patients. (See
Table 2.)
Ischemia Severity and Effect of Bypass Grafting
Table 3 summarizes the average
annual risks (AARs) and 5-year rates of initial cardiac events and
causes of cardiac deaths during medical follow-up or of initial events
after CABG. When the clinical course of patients who underwent CABG
(early or late) was compared with the experience of the
medical-treatment-only patients (Figure 1), the non-CABG patients progressed both
to cardiac death and to major cardiac events somewhat more rapidly than
the surgically treated patients, although these differences were not
statistically significant (P=NS for cardiac death,
P<0.10 for cardiac events). However, when patients were
stratified according to preoperative ischemia severity,
significant intragroup differences in CABG effect were observed.
Outcome in patients without severe ischemia (LVEF more than
-8%) who did not undergo surgery was relatively benign despite the
presence of 3-vessel disease and was indistinguishable from that in
CABG patients who had a comparable degree of ischemia before
surgery (Figure 1). When the nonseverely ischemic
patients were further stratified post hoc according to magnitude and
direction of LVEF (ie, >0% versus 0% to -7%), more deaths and
major cardiac events were observed when LVEF was 0% to -7%.
However, CABG did not alter the expected natural history of the
minimally or modestly ischemic subgroups. In contrast, among
patients with LVEF of -8% or less, CABG improved expected outcome
(4-fold mortality rate reduction [P=0.02], 3-fold event
rate reduction [P=0.01]; Table 3; Figure 1).
CABG also produced significant life-prolonging (P<0.05) and
event-reducing (P=0.02) benefit when the analysis
included the postoperative course of 8 severely ischemic
patients who suffered intercurrent MI before operation (Table 3). Cox model analysis revealed a statistically
significant (P=0.04) direct relation between preoperative
ischemia severity and benefit from CABG (Figure 2). Relative hazards were approximately
equivalent among medical-treatment-only versus CABG patients with no or
relatively mild ischemia at initial study and rose 5-fold among
the most severely ischemic medical-treatment-only patients
versus CABG patients.
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Timing of Operation and Effect of Bypass Grafting
The interval between initial testing and operation also influenced
outcome. Early CABG patients uniformly underwent operation 1 month
after initial radionuclide study; for late CABG patients, this hiatus
averaged 14.5 months. Events were less frequent in early than in late
CABG patients: AARs of cardiac death and major cardiac events were
6-fold and 3-fold lower, respectively, among early CABG patients
(P<0.04 for cardiac death, P<0.06 for cardiac
events; Table 3; Figure 3). Among
early CABG patients, no cardiac deaths (and only 1 nonfatal MI, at 3
years) occurred until >5 years after surgery. In contrast, among late
CABG patients who underwent surgery without intercurrent event between
radionuclide study and operation, 1 nonfatal MI and 6 cardiac deaths
occurred within 5 years of follow-up. When the postoperative experience
of patients with intercurrent events was included in analysis,
the advantage of early operation was even more pronounced
(P=0.02 for cardiac death; P=0.04 for cardiac
events).
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Early CABG patients also suffered 6-fold fewer cardiac deaths
(P<0.05) and 4-fold fewer major cardiac events
(P<0.02) than medical-treatment-only patients (Table 3; Figure 4). The influence of
early CABG depended on the preoperative severity of exercise-induced LV
dysfunction. When the effects of early CABG were evaluated separately
among patients without severe preoperative ischemia (LVEF
more than -8%), CABG produced no life-prolonging or event-reducing
benefit. When the nonseverely ischemic patients were further
substratified to separately examine the course of those with LVEF
>0% and LVEF 0% to -7% at initial study, CABG produced no
survival benefit in either subgroup, although major cardiac events
trended downward (P<0.07) among patients with LVEF 0%
to -7% (Table 3). Among patients with LVEF >0%, no
cardiac deaths occurred in medical-treatment-only or CABG patients, and
only 1 nonfatal MI occurred, 7 years after initial study, in a non-CABG
patient. In contrast, significantly fewer cardiac deaths
(P<0.02) and total cardiac events (P=0.008)
occurred among patients with severe preoperative ischemia
(LVEF -8% or less) who underwent early CABG than among similarly
ischemic patients who remained surgery-free throughout
follow-up (Figure 4). AARs of cardiac death and events among
severely ischemic early CABG patients were reduced 9-fold and
5-fold, respectively, compared with corresponding
medical-treatment-only patients (Table 3); these differences
were maintained throughout follow-up (Figure 4).
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The effect of CABG was less apparent when operation was deferred >1
month after ischemia had been defined (Table 3; Figure 4). For late CABG patients without MI between initial
radionuclide study and operation, CABG did not prolong life compared
with medical therapy alone, although severely ischemic (LVEF
-8% or less) patients tended (P=0.09) to have fewer major
cardiac events when they underwent CABG late than did comparably
ischemic medical-treatment-only patients (Table 3;
Figure 5). This apparent surgical
advantage is approximately half of that achieved in parallel early CABG
patients and was abolished when analysis included the
postoperative experience of the 10 late CABG patients with MI between
initial study and operation.
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Prognostic Indexes
As among the medical-treatment-only patients,
univariate analysis in the
expanded-medical-treatment group identified a relationship between
LVEF at initial study and the likelihood of subsequent cardiac death
or nonfatal MI (P<0.01; Figure 5). LVEF also
significantly (P=0.03) predicted this outcome when
analysis was restricted to the 53 patients with 70%
stenoses.
Among the 16 patients whose LVEF increased with exercise, only 2
nonfatal MIs and no cardiac deaths occurred during follow-up. The AAR
of major cardiac events in this subgroup was almost 2-fold less than
among the 32 patients whose LVEF either was unchanged or fell 7%
with exercise and >5-fold less than among the 51 patients whose LVEF
fell 8% with exercise (P<0.01; Figure 5; Table 3). Major cardiac events were unrelated to absolute LVEF at
rest, blood pressure, exercise heart rate, exercise tolerance, or
clinical variables (including age, MI history, and long-term use of
antianginal medications) but were related to CAD severity (by Gensini
score; P<0.03) and tended to be related to absolute LVEF at
peak exercise (P=0.06). By multivariate
analysis, LVEF was the most potent independent predictor of
initial major cardiac events (P=0.003), followed by Gensini
score (P=0.02). Absolute exercise LVEF added no independent
information. LVEF remained predominantly and independently
predictive even when clinical, hemodynamic, and
exercise tolerance data were forced into the model on a post hoc
basis.
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Discussion |
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Our data indicate that the benefit of CABG among patients with 3-vessel CAD varies directly with the direction and magnitude of
LVEF measured before operation. Thus, these data can facilitate
management decisions. Although no previous investigators have
undertaken this analysis, our data are consistent with
and extend those of 2 previous reports in which preoperative LVEF with
exercise was used to identify patients likely to benefit from CABG.
Jones and coworkers12 found that the concomitant presence
of 3-vessel or left main disease and a positive exercise radionuclide
angiogram (either LVEF 0% or exercise-induced worsening in wall
motion or increase in end-systolic volume >20 mL with
exercise) predicted CABG-associated benefit at 3 years among patients
with mildly to markedly subnormal LVEF at rest. The prognostic value of
the LVEF exercise response was not evaluated among those with 3-vessel
disease alone, and the influence of ischemia severity on
prognosis was not examined. In a later report, Jones13
extended these findings through 4 years, additionally widening the
range of LVEF at rest for study inclusion. The present study indicates that among patients with CAD and sufficient exercise-inducible ischemic dysfunction to benefit from CABG, benefit diminishes as the interval between definition of ischemia and operation increases, presumably due to widespread CAD progression during the interval. No previous study has evaluated this issue.
Our data also indicate a significant relation between LVEF exercise
response and subsequent outcome among clinically stable, nonsurgical
patients with angiographically confirmed 3-vessel CAD and normal or
near-normal LVEF at rest. LVEF strongly predicts major cardiac
events in this population whether 3-vessel disease is defined as 50%
or 70% luminal narrowing. Our results are consistent with
previous reports of prognostic value of the LV exercise response
(LVEF1 6 or absolute exercise LVEF3 ) in
this population1 3 6 and also among medically treated
patients with 1- or 2-vessel CAD and LV dysfunction at
rest32 33 and those not stratified for CAD
severity.2 3 4 5 Most previous studies of 3-vessel disease
have dichotomized patients,1 6 7 32 33 although some also
analyzed exercise LVEF as a continuous variable; the
majority demonstrated that those with ischemia have poorer
outcomes than those without.1 6 7 32 Our results confirm
these findings by demonstrating a direct relation between the magnitude
of LVEF exercise response and likelihood of cardiac events, including
cardiac death. Thus, our observations indicate that for a patient with
3-vessel disease whose LV performance is normal or near normal
at rest, prognosis can be inferred relatively precisely from the
direction and magnitude of LVEF. Moreover, the present study
indicates that among patients with clinically stable 3-vessel disease,
the prognostic value of a single determination of LVEF maintains its
significance for many years, during a more prolonged period than can be
inferred from earlier studies. The present findings are at variance
with 2 investigations7 8 that failed to identify a
relation between exercise-induced LV dysfunction and outcome in
patients with 3-vessel disease. However, 1 of these
studies7 involved only 53 patients and a relatively short
median follow-up (22 months); the other failed to analyze the
effect of ischemic dysfunction alone, instead prespecifying a
compound ECG-LVEF-exercise tolerance–based criterion that was absent
in all 42 study patients.8
Patient selection and other design differences preclude direct comparison between the present study and the 3 large randomized trials of CABG.9 10 11 None of the CABG trials assessed exercise-inducible ischemia at study entry in all patients. However, available exercise ECG data suggest different distribution of ischemia severity at entry among the different trials,9 34 whereas post hoc analysis of the available sample in 1 trial found that surgical benefit in patients with 3-vessel disease and preserved LV function was related to preoperative exercise ECG results.14 35 Therefore, consistent with the suggestion of Bonow and Epstein,34 the interaction between baseline ischemia severity and surgical benefit observed in the present study may help to explain the discordant findings among the CABG trials regarding patients with 3-vessel CAD.
The present results suggest that 3-vessel disease does not necessarily require surgery for beneficial alteration of natural history. Without operation, patients with minimal or modest exercise-induced ischemic dysfunction can expect prolonged survival with relatively low risk of intercurrent MI. Such patients are relatively common even among those referred to a large tertiary care center. However, the progressive nature of CAD suggests the prudence of periodic reevaluation of clinically stable patients. Our results provide no insight into the appropriate intertest interval, and additional study is needed.
The present study used radionuclide cineangiography for assessment
of LVEF. However, the prognostic implications of LVEF are likely to
be applicable to results obtained with other techniques, including
echocardiography15 and myocardial
perfusion scintigraphy with
99mTc-based radionuclides,16 which
are now frequently used to measure LVEF during exercise. Nevertheless,
direct application of these data with other techniques requires
determination of the precision of the alternative methods in emulating
radionuclide cineangiographic LVEF.
Study Limitations
Our findings are limited by the relatively modest size of the
cohort and number of end points observed. Cardiac deaths were few and
attributed to various causes (Table 3) among medically treated
patients, precluding prediction of this outcome alone. Prognostic
inferences were defined only for relatively broad LVEF ranges and
intervals between testing and operation. Relatively few patients who
underwent surgery manifested a minimal fall or a rise in LVEF with
exercise, which limits the statistical power for detecting treatment
differences among those with little or no ischemia. Allocation
to medical or surgical therapy was determined by the patient's
physician, which would potentially bias the results. However, CABG and
non-CABG patients were comparable on most baseline variables; where
differences existed, baseline morbidity was greater among CABG patients
than medical-treatment-only patients. Thus, baseline differences are
unlikely to account for surgical benefits among CABG versus non-CABG
patients. Patients were enrolled in the present study based on
referral for exercise radionuclide cineangiography; our cohort is not a
consecutive series of patients with 3-vessel disease referred to this
hospital or seen by any referring physician, which suggests possible
unintentional selection bias. However, previous research in this
laboratory27 has not disclosed any important clinical,
arteriographic, or survival differences between patients undergoing
radionuclide cineangiography and comparable patients in our institution
not undergoing such testing. Therefore, our study patients probably
reasonably represent the general population with anatomically
similar disease.
Of necessity in an investigation designed for long-term follow-up,
initial study was performed >10 years ago, when most patients in our
institution received saphenous vein grafts during CABG; current
practice favors internal mammary artery plus vein grafting for 3-vessel
disease.36 These differences, and newer refinements
in surgical technique, may affect the quantitative extrapolation of our
results. Study is required to determine precisely the prognostic value
of preoperative exercise LVEF response among patients who undergo
surgery in the present day. Nonetheless, our results
indicate that even with vein bypasses, CABG produces natural history
benefit for patients with 3-vessel disease and functionally severe
ischemia; this benefit and its direct relation to LVEF are
likely to be similar or greater with internal mammary artery grafting.
Conversely, the present data indicate that absence or minimal
abnormality in the LVEF exercise response predicts a benign natural
course without surgery; these results should be unaffected by newer
surgical techniques. However, our middle group, manifesting moderate
exercise-induced ischemic dysfunction, requires additional
study, because trends toward CABG benefit may reach significance with
application of more effective surgical therapies.
Finally, for reasons previously stated, patients were excluded from this evaluation if LVEF was <30% at rest. Patients manifesting this characteristic represent <10% of those seen in our laboratory.4 They also were excluded if they had previously undergone surgery or had nonischemic cardiac comorbidity or life-limiting noncardiac disease (<40% of evaluable patients). Therefore, although our results should be applicable to the majority of patients with 3-vessel CAD, additional study is needed to extrapolate our results to the more severely compromised patient.
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Acknowledgments |
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Dr Borer was supported in part as an Established Investigator of the American Heart Association during a portion of this study and is supported in part by an endowment from the Gladys and Roland Harriman Foundation, New York, NY, as the Gladys and Roland Harriman Professor of Cardiovascular Medicine, Weill Medical College of Cornell University. This study was supported primarily by a grant from The Howard Gilman Foundation, New York, NY. Additional support was provided by the Ray Corbett Heart Fund, Saratoga, NY; the Slaner Foundation, New York, NY; the Daniel and Elaine Sargent Charitable Trust, New York, NY; the David Margolis Foundation, New York, NY; the Charles and Jean Brunie Foundation, Bronxville, NY; the Mary A.H. Rumsey Foundation, New York, NY; the Irving A. Hansen Foundation, New York, NY; and by much appreciated gifts from Ronald and Jean Schiavone, Mary Jane Voute Arrigoni and the late William Voute, and Stephen and Suzanne Weiss. The authors thank John Teevan, BA, and Jason Spector, MD, for their efforts in data collection and computer data entry, and Martin Lesser, PhD, for his guidance in statistical data analysis.
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Footnotes |
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Reprint requests to Jeffrey S. Borer, MD, The New York Presbyterian Hospital–Weill Cornell Medical Center, 525 E 68th St, New York, NY 10021.
Received March 18, 1999; revision received May 26, 1999; accepted June 2, 1999.
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