The Appropriate Cardiac Evaluation for Peripheral Vascular
Disease Patients
Charles O Brantigan, MD
There is a very high incidence of coronary artery disease (CAD)
in patients with peripheral vascular disease (PVD). The mortality
rate of PVD patients from CAD is high irrespective of treatment. For
years there has been the hope that if the CAD is sought
preoperatively through a complete cardiac work-up, then
interventions could be made which would minimize subsequent
mortality. Unfortunately the morbidity of the cardiac work-up, the
morbidity of the subsequent treatment and the relative lack of
effectiveness of the treatment have led to the selective application
of a "full cardiac work-up" in these patients. The
decision making process with limb salvage patients is further
complicated because the cardiac work-up delays the attempt to save
the limb. That might be justified on the basis of "life over
limb," but there is no evidence that the overall mortality of
combined cardiovascular and peripheral vascular procedures is less
than simply saving the limb (providing that the patients
hemodynamics are aggressively managed). Over the past few years
surgeons in major referral centers have simply assumed that
peripheral vascular disease patients, particularly those considered
for limb salvage procedures, all have CAD and have managed them
accordingly. Those selected for coronary arteriography are those
with ongoing cardiac ischemic symptoms, particularly those who need
elective vascular reconstructions.
Incidence and impact of CAD
In one of the earliest studies of CAD and PVD, Hertzer of the
Cleveland Clinic described the results of coronary arteriography in
elective PVD patients1. These patients did not have as severe PVD
as we commonly see today. In the first place, many patients whose
disease was so severe as to be considered inoperable in 1980 would
be considered operable now. In the second place patients with urgent
problems or limb salvage as their indication for vascular surgery
were excluded. All other patients had coronary arteriograms. The
coronary arteries were characterized as normal in 8%, mild to
moderately diseased in 32%, severely diseased but compensated in
29%, severely diseased and surgically correctable in 25% and
severely diseased and not correctable in 6%. Thus 92% had CAD. For
the 25% with severe correctable CAD, coronary artery bypass grafting
(CABG) was recommended. The mortality was 5.3%, which should be
compared to 1.2% they were reporting for their usual patients at
that time. The authors noted that the mortality rate of 5.3% was
higher than expected, but in line with the experience of others in
operating on high risk patients. Morbidity was not discussed. CABG
did make PVD surgery safer. In noting that the combined mortality of
CABG plus peripheral reconstruction was the same as for peripheral
reconstruction alone, they clearly did not consider the patients who
died from CABG, as the mortality for combined procedures was less
than the mortality for CABG. Hertzer noted that his recommendations
are controversial, but that he recommends coronary arteriography
before peripheral vascular reconstruction. In 1989 Hertzer reported
the longer-term results of this strategy in discussion of a paper by
another author2. This aggressive strategy appeared to work in
non-diabetic men on a long-term basis. These patients experienced a
22% mortality or a 6.3% cardiac mortality at 5 years, results
comparable to non-PVD patients undergoing CABG. All others
(diabetics, women, etc) fared worse, experiencing a 40% mortality or
a 23% cardiac mortality in 5 years.
Peripheral vascular disease is a marker for early mortality in
coronary artery disease patients with or without surgical treatment
of the CAD. Eagle et al, in a widely quoted study3, reported the
results of the Coronary Artery Surgery Study (CASS). 16 249 patients
were enrolled in the study between 1974 and 1979 and then randomized
into medical and surgical treatment of their CAD. Of this group
2,296 had markers of PVD. At any point in time over the ten-year
period, the patient with vascular disease had a 25% increased risk
of dying after controlling for all other factors. Cerebrovascular
disease, interestingly, was worse with a 43% greater risk of death
over time. Peripheral vascular disease was a strong independent
predictor of long- term mortality in patients with stable coronary
artery disease. They did not give data for PVD with CABG vs. PVD
without CABG as they did for the other variables, but it is included
in the "all other factors." This is a less severe subset
of PVD patients, as they were patients identified with markers for
PVD and were not patients proposed for arterial
reconstruction.
The presence of peripheral vascular disease has an adverse impact
on the outcome of CAD treatment that is independent of the fact that
these patients have more comorbid conditions. Birkmeyer, McDaniel et
al in a study of 3003 patients4, compared the short-term results
of CABG in patients with and without PVD. Clinical and subclinical
indicators of PVD led to a 2.4 fold higher mortality (7.7% compared
to 3.2%). Even after adjusting for all comorbidities, PVD patients
had a 73% higher chance of dying during a hospitalization for CABG
than other patients. Note that this study includes patients with PVD
not severe enough to merit intervention and therefore is not exactly
applicable to the limb salvage patient. "Controlled studies of
the long-term effects of CABG in patients with PVD are needed to
determine the optimal role of myocardial revascularization in this
population."
Mesh et al (1997)5 noted that CABG was a relatively high risk
procedure in PVD patients. They studied a group of 680 patients
undergoing CABG. 58 had a standard indication for, or a history of,
vascular reconstruction. Limb salvage patients were excluded.
Vascular patients experienced a 5.2% mortality from the CABG while
those without clinical PVD had only a 2.3% mortality (p=.09). Major
morbidity was 3.6 fold higher in patients with PVD compared with
those without. "Such morbidity may preclude or alter the timing
of subsequent vascular reconstruction."
PVD has an adverse result on the outcome of coronary balloon
angioplasty as well. Sutton-Tyrrell studied the effect of PVD on the
long term outcome of patients with CAD undergoing balloon
angioplasty6. The 5 year survival of PVD patients was 75.8%
compared for 90.2% of those without PVD. If anything, this study
underestimated the difference, as the patients with PVD included
those not severe enough to undergo PVD surgery. In addition the
proportion of PVD patients who are candidates for balloon
angioplasty instead of CABG is low compared to the general
population of CAD patients.
The presence of PVD adversely affects the longer term outcome of
CABG. Birkmeyer7, McDaniel et al reported a study of 2871 patients
discharged alive after CABG and noted that the 5 year mortality in
PVD patients was 20% compared to 8% for the others. Again, these
patients did not necessarily have severe enough PVD to merit
surgical reconstruction. In their opinion, whether myocardial
revascularization successfully reduces long term mortality in
patients with PVD is unclear. Those with multilevel vascular disease
had especially high mortalities. They gave three possible
explanations for their observations:
- Peripheral vascular disease is a marker for diffuse coronary
disease not as amenable to complete correction.
- PVD may be a marker for "virulent atherosclerosis."
- PVD patients may have increased mortality due to sequellae of
their noncardiac arterial disease, including stroke, mesenteric
ischemia and lower extremity complications.
They concluded that "The presence of clinical or subclinical
PVD is important when predicting both short- and long-term outcomes
in patients considering coronary artery bypass surgery."
We can conclude from these and many other studies that most PVD
patients have CAD. CAD is the most common cause of death in PVD
patients, but these patients are at markedly increased risk for the
various interventional strategies designed to treat CAD. These
patients do poorly with treatment of their CAD. A consensus has
emerged that subjecting all of these patients to coronary
angiography is very expensive and not practical. Many other
strategies and screening tests have been proposed to select out the
patients that would benefit from prophylactic coronary
revascularization.
Testing and Screening Strategies
Echocardiography had been proposed as a screening strategy to
identify patients with a decreased ejection fraction. A decreased
ejection fraction is a marker for poor ventricular function, and as
such is a marker for poor surgical outcome. It does not measure
cardiac function in an ongoing way, however. In addition patients
with diastolic dysfunction may have a normal ejection fraction. For
these reasons, cardiac tuning in patients in severe congestive heart
failure treatment protocols is usually accomplished using invasive
monitoring instead because it is more accurate. Braunwald calls this
"tailored therapy8." Echocardiography has been
enhanced by administration of dobutamine, an inotropic agent that
increases oxygen demand and leads to dysfunction of myocardial wall
segments that have compromised blood supply. This dysfunction can
then be visualized by echocardiography. Shafritz et al (1997)
studied the utility of dobutamine echocardiography in evaluating
patients for elective aortic surgery. In 110 patients there was no
statistically significant difference in overall mortality or cardiac
mortality between the two groups. The patients were managed
aggressively during surgery with invasive monitoring. In spite of
these data, they recommend screening in all patients scheduled for
elective aortic surgery unless they have a negative coronary disease
history, normal EKG and no active cardiac symptoms9.
Treadmill stress tests have been proposed as a method of
screening for coronary artery disease. While widely used, they are
relatively insensitive and non specific. In addition, many patients
proposed for vascular surgery can not walk far enough for a
successful test or they wouldn't have been proposed for vascular
surgery in the first place. Dipyridamole thallium scintigraphy (DTS)
has been proposed as a way to compensate for these weaknesses. The
heart is scanned after administration of radioactive thallium, which
shows the perfusion of the heart. Dipyridamole (persantine) is then
given as a vasodilator. If there is a fixed deficit, that area of
myocardium is believed to be a scar with little or no perfusion. If
redistribution of the isotope is seen after vasodilation, then the
myocardium is believed to have an area of inadequate perfusion. This
test correlates well with the results of coronary arteriography, but
not with whether the coronary artery disease is amenable to
surgery.
Cutler and Leppo10 used persantine thallium scanning on 116
patients scheduled for aortic reconstruction. The management
strategy varied during the series. 51 patients had abnormal studies
of which 20 underwent coronary angiography. This procedure resulted
in 1 death from a ruptured aneurysm and 1 stroke. Six patients
underwent CABG of which 1 died of pancreatitis, producing a 16.7%
mortality attributable to the CABG alone. All patients who died in
the series did so as a result of the screening strategy. Based on
these data, they recommended routine screening.
Schueppert et al (1996)11 studied the value of preoperative
cardiac screening with DTS and radionuclide ventriculography (RNV)
in vascular patients. RNV provides information roughly equivalent to
the ejection fraction determined by echocardiography. "The
finding of severe coronary artery disease led to cardiac
revascularization in 17 patients who had no prior history of cardiac
disease and 13 patients with a history of angina or myocardial
infarction. Two deaths and nine major complications were associated
with coronary arteriography and cardiac revascularization."
Routine screening did not result in substantial benefit. They
concluded that screening may have a more important role in patients
with less compelling or entirely elective indications for peripheral
vascular surgery.
Kresowick reported the University of Iowa experience with cardiac
screening of vascular surgery patients with DTS in 1997. Patients
with recent coronary revascularization or unstable angina were
excluded. In 1989 and 1990 they screened 394 consecutive candidates
for vascular reconstruction with DTS. 169 patients had a reversible
deficit. Of these patients 136 underwent coronary angiography. This
procedure produced 1 death and 4 arterial complications requiring
surgery. 30 of these patients underwent coronary revascularization
(CABG/PTCA).. The mortality was 4.5% with 23% major morbidity. The
percentage of interventions per coronary angiogram seems small and
not particularly cost effective. 36 patients, or 9.1% did not have
vascular surgery because they were considered high risk and their
proposed procedure was elective. Of the 343 patients undergoing
vascular surgery the mortality was 1.7% with a 3.2% incidence of
perioperative myocardial infarction. Thus the risk of the
prophylactic myocardial revascularization was higher than the
mortality of the vascular surgery. Their results led to a more
selective screening process. Their selection protocol became based
on whether the information would change the management strategy.
Screening is most valuable for patients in whom no vascular surgery
is an option. In the case of limb threatening ischemia, these
patients have the highest cardiac risk, but non surgical therapy for
their peripheral vascular problem is not an option. These same
patients are not good candidates for coronary revascularization.
Considering that these patients can undergo vascular surgery with an
acceptable risk, the risks of screening and prophylactic treatment
of coronary artery disease outweigh the benefits.
Massie et al (1996)12 reported the impact of routine screening
of 934 vascular patients with DTS prior to surgery. 297 patients had
2 or more segments of redistribution. Of these, 70 patients had
coronary angiography. From the remaining 227 patients, 70 were
matched to the coronary angiography group according to risk factors.
Of the coronary angiography patients 25% underwent revascularization.
This resulted in 3 deaths and 2 myocardial infarctions. The
survivors and all of the second group underwent peripheral vascular
surgery. The incidence of perioperative non fatal myocardial
infarction, perioperative fatal myocardial infarction, late non
fatal myocardial infarction and late cardiac death was the same in
both groups. Thus, not only was there no advantage to intensive
screening and coronary revascularization, but there was significant
additional morbidity and mortality. They concluded that the risk of
extended cardiac evaluation and treatment did not produce any
improvement in either the perioperative or long-term survival
rate.
Seeger et al (1994)13 began with the premise that since cardiac
complications are a major cause of death and morbidity following
aortic reconstruction, that identifying these patients by
stress-thallium scanning would allow coronary arteriography and
coronary interventions as appropriate, and would lead to decreased
mortality for aortic reconstruction. They compared 146 candidates
for elective aortic reconstruction who had routine stress thallium
scans as a part of their work-up with 172 patients who did not. Of
the screened patients, 41% underwent coronary arteriography compared
to 14.7% in the unscreened group. There were 11.6% incidence of
CABG/PTA compared to 4.1% in the patients not screened. Stress
thallium scanning documented the known high incidence of CAD in PVD
patients but provided no other benefit There was no difference in
the incidence of fatal postoperative myocardial infarction, serious
postoperative myocardial events, overall postoperative cardiac
complications or long term survival between the groups. It appears
that the added morbidity and mortality of the screening/coronary
arteriography, revascularization was not considered. They considered
the possibility that other screening tests might be of more value
and considered ejection fraction, preoperative electrocardiographic
monitoring for silent ischemia, treadmill exercise cardiac stress
testing and dobutamine echocardiography. All of these tests had the
same limitations as did stress thallium testing. All of the
screening tests are reasonable good at picking out the patients who
will do well with peripheral vascular surgery, but what is really
needed is a way to select the patients who will not. They concluded
that the risk and expense or routine preoperative cardiac screening
and prophylactic cardiac revascularization can not be justified in
patients undergoing peripheral vascular surgical procedures.
Basically, their recommendations are that testing for CAD needs to
be done based on clinical considerations and not for
screening.
Other screening strategies have been proposed and evaluated.
Gajraj and Jamieson14 reviewed the role of screening strategies for
cardiac disease prior to peripheral revascularization. They
concluded that, although CAD accounts for much of the mortality
associated with surgery for PVD, routine coronary arteriography and
prophylactic myocardial revascularization is not of any practical
value. In patients with clinical evidence of CAD, the operative
mortality of vascular surgery is nearly 7%, but the operative
mortality for CABG is 5-10% in this same group of patients. The
combined mortality of the two procedures provides little benefit
even in this relatively high risk group of patients. "The
authors believe that the following policy is consistent with the
data that have been presented. Patients without clinical evidence of
CAD may proceed to surgery without further investigation. Patients
with a history of CAD that is stable and not severely limiting
should be monitored carefully in the perioperative period. Those
with severely symptomatic CAD should be assessed by a
cardiologist." Peripheral vascular surgery is not an indication
for cardiac screening or prophylactic myocardial revascularization.
D'Angelo et al (1997)15 discussed the role of cardiac evaluation
in the patient undergoing aortic reconstruction. They compared
patients who had been screened by varying strategies with those who
had not. There was no difference in mortality or morbidity.
Considering that the overall mortality in his series of aortic
reconstructions was 2.7% it would be hard to justify adding an
additional similar mortality that would result from preoperative
CABG. "Of course, any patient with cardiac symptoms that on
their own warrant further investigation should be fully evaluated
before elective surgery."
Mason et al did a decision analysis of various strategies to
prevent cardiac morbidity in patients with mild angina or no angina
and a positive dipyridamole thallium scan (DTS). Excluded from the
study were patients, such as limb salvage patients, with urgent need
for vascular surgery. Vascular disease was assumed to be the
dominant clinical problem. Patients with severe angina were
excluded. Their dominant clinical problem was considered to be
cardiac and the cardiac disease was treated first. Mason et al
concluded that proceeding directly to vascular surgery would produce
the best clinical results because of the additional morbidity risk
of the cardiac procedures. They noted that, "The results of
this analysis may appear counterintuitive: How can overall outcome
not be improved if PTCA and CABG reduced perioperative cardiac risk
by one half to two thirds? The answer appears to lie in the
observation that the coronary angiography strategy commits the
patient to undergo three procedures (coronary angiography, coronary
revascularization, and finally vascular surgery), whereas this
vascular surgery strategy exposes the patient to just one procedure.
In running the gauntlet of three procedures, the patient must face
the risk of death, myocardial infarction, and stroke three times,
and therefore the cumulative procedural risk outweighs the
benefit." They concluded that coronary angiography and
myocardial revascularization in patients with symptomatic peripheral
vascular disease is associated with morbidity and mortality rates
substantially higher than in patients with symptomatic CAD alone.
For this reason "full cardiac work-up" should be reserved
for patients whose dominant clinical problem is CAD16.
Summary
All vascular surgeons are engaged in a quest to find ways to
decrease the morbidity and mortality of vascular reconstructive
surgery. Although PVD patients are beset by a wide variety of other
diseases including diabetes, renal failure, wounds, infections and
the like, their leading source of mortality is coronary artery
disease. Many strategies have been proposed for dealing with the
associated CAD ranging from submitting all to coronary arteriography,
to screening all patients with one test or another, to selectively
screening patients based on various criteria, to not screening at
all. All of the proposed screening tests succeed in identifying
patients who will do well with reconstructive surgery. None are very
specific in picking the ones who will not do well. There is question
concerning the effectiveness of the various interventional
strategies once critical CAD is found. Not only do PVD patients have
higher comorbidity than routine CAD patients, but PVD is an
independent marker for increased morbidity and mortality for
coronary interventions, both on a short and long term basis. In
addition, the group of vascular patients with the highest expected
cardiac mortality and morbidity are the limb salvage patients. Their
vascular operations are not elective and can not be delayed. They
have been historically operated on with a mortality rate less than
the mortality of CABG providing that they receive good critical care
during the perioperative period. If coronary screening has a role in
PVD, it is in the elective patient, the patient whose vascular
disease is not critical. These are the patients who will have the
best short term and long term results from coronary
revascularization. The best strategy for managing combined CAD and
PVD appears to be based on clinical judgement. Patients whose
clinical presentation includes indications for a coronary
intervention should be tested and treated for this. Those whose
clinical presentation is one of PVD should simply undergo the
peripheral reconstruction, using careful monitoring and management
that assumes that there is associated coronary disease.
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