GIBBONS
ET AL., MANAGEMENT OF PATIENTS WITH CHRONIC STABLE ANGINA UPDATE
http://www.acc.org/clinical/guidelines/stable/update_index.htm
ACC/AHA
2002 Guideline Update for the Management of Patients With Chronic
Stable Angina
A
Report of the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines (Committee to Update the 1999
Guidelines for the Management of Patients With Chronic Stable Angina)
This
is a Guideline Update of the 1999 Chronic Stable Angina Guidelines.
To highlight the changes, deleted text is indicated by strikeout,
and revised text is presented in brown. A clean version of the document,
with changes fully incorporated, is available for download and print.
III.
Risk Stratification
A.
Clinical
Assessment
1.
Prognosis of CAD for Death or Nonfatal MI: General Considerations
Coronary
artery disease is a chronic disorder with a natural history that
spans multiple decades. In each affected person, the disease typically
cycles in and out of clinically defined phases: asymptomatic, stable
angina, progressive angina, and unstable angina or acute MI. Although
the specific approach to risk stratification of the coronary disease
patient can vary according to the phase of the disease in which
the patient presents, some general concepts apply across the spectrum
of disease.
The
patient’s risk is usually a function of four types of patient
characteristics. The strongest predictor of long-term survival with
CAD is the functioning of the LV. Ejection fraction is the most
commonly used measure of the extent of LV dysfunction. A second
patient characteristic is the anatomic extent and severity of atherosclerotic
involvement of the coronary tree. The number of diseased vessels
is the most common measure of this characteristic. A third characteristic
provides evidence of a recent coronary plaque rupture, which indicates
a substantially increased short-term risk for cardiac death or nonfatal
MI. Worsening clinical symptoms with unstable features is the major
clinical marker of a plaque event. The fourth patient characteristic
is general health and noncoronary comorbidity.
The
probability that a given patient will progress to a higher-or lower-risk
disease state depends primarily on factors related to the aggressiveness
of the underlying atherosclerotic process. Patients with major cardiac
risk factors, including smoking, hypercholesterolemia, diabetes
mellitus, and hypertension, are most likely to have progressive
atheroscle rosis with repeated coronary plaque events. Patients
presenting at a younger age also may have more aggressive disease.
A
growing body of pathologic, angiographic, angioscopic, and intravascular
ultrasonographic data support a pathophysiologic model in which
most major cardiac events are initiated by microscopic ulcerations
of vulnerable atherosclerotic plaques. Several lines of evidence
have shown that the majority of vulnerable plaques appear “angiographically
insignificant” before their rupture (less than 75% diameter
stenosis). In contrast, most of the “significant” plaques
(greater than 75% stenosis) visualized at angiography are at low
risk for plaque rupture. Thus, the ability of stress testing of
any type to detect vulnerable atherosclerotic lesions may be limited
by the smaller size and lesser effect on coronary blood flow of
these plaques, which may explain the occasional acute coronary event
that occurs shortly after a negative treadmill test result.
2.
Risk Stratification With Clinical Parameters
Rigorous
evidence for predictors of severe CAD (three-vessel and left main
disease) derived solely from the history and physical examination
in patients with chest pain is surprisingly limited. Presumably,
this is because physicians routinely incorporate additional information
(e.g., an ECG) into risk stratification.
Nevertheless,
very useful information relevant to prognosis can be obtained from
the history. This includes demographics such as age and gender,
as well as a medical history focusing on hypertension, diabetes,
hypercholesterolemia, smoking, peripheral vascular or arterial disease,
and previous MI. As previously discussed, the description of the
patient’s chest discomfort can usually be easily assigned
to one of three categories: typical angina, atypical angina, and
nonanginal chest pain (38).
The
physical examination may also aid in risk stratification by determining
the presence or absence of signs and symptoms that might alter the
probability of severe CAD. Useful findings include those that suggest
vascular disease (abnormal fundi, decreased peripheral pulses, bruits),
long-standing hypertension (blood pressure, abnormal fundi), aortic
valve stenosis or idiopathic hypertrophic subaortic stenosis (systolic
murmur, abnormal carotid pulse, abnormal apical pulse), left-heart
failure (third heart sound, displaced apical impulse, bibasilar
rales), and right-heart failure (jugular venous distension, hepatomegaly,
ascites, pedal edema).
Several
studies have examined the value of clinical parameters for identifying
the presence of severe (three-vessel or left main) CAD. Pryor et
al. (134) identified 11 clinical
characteristics that are important in estimating the likelihood
of severe CAD: typical angina, previous MI, age, gender, duration
of chest pain symptoms, risk factors (hypertension, diabetes, hyperlipidemia,
smoking), carotid bruit, and chest pain frequency. In a subsequent
study, Pryor et al. (41) provided
detailed equations for the prediction of both severe CAD and survival
based on clinical parameters.
Hubbard
et al. (351) identified five clinical
parameters that were independently predictive of severe (three-vessel
or left main) CAD: age, typical angina, diabetes, gender, and prior
MI (history or ECG). Hubbard then developed a five-point cardiac
risk score. A composite graph (Fig.
7) estimates the probability of severe CAD. Each curve shows
the probability of severe CAD as a function of age for a given cardiac
risk score. As shown on this graph, some patients have a high likelihood
(greater than 1 chance in 2) of severe disease on the basis of clinical
parameters alone. Such patients should be considered for direct
referral to angiography, because noninvasive testing is highly unlikely
to be normal and, if it is, may conceivably be false-negative. An
example would be a 50-year-old male patient with diabetes, taking
insulin, with typical angina and history and ECG evidence of previous
MI. His estimated likelihood of severe disease is 60%; such a patient
should be considered for angiography without further testing.
Descriptive
information about the chest pain is very important in assessment
of patient prognosis and risk of severe CAD. However, because the
extent and location of angiographically demonstrated occlusion,
together with the degree of LV dysfunction, appear to have substantially
greater prognostic power than symptom severity (96,352),
many clinicians have come to rely almost exclusively on these “objective”
measurements of disease and very little on the patient’s history
in choosing among the alternative management strategies for their
patients. However, clinical parameters should not be ignored for
risk stratification (41,353,354).
Califf et al. (95) have provided
evidence that the aggregation of certain historical and ECG variables
in an “angina score” offers prognostic information that
is independent of and incremental to that detected by catheterization.
The angina score was composed of three differentially weighted variables:
the “anginal course,” anginal frequency, and rest ECG
ST-T-wave abnormalities. Two features of the prognostic power of
the angina score seem intuitively correct: 1) it had a greater impact
on short-term prognosis than long-term prognosis, presumably reflecting
the importance of a plaque rupture; and 2) it had greater prognostic
value when the LV was normal than when it was abnormal, presumably
because so much of the overall prognosis was determined by LV function
when it was abnormal.
Peripheral
vascular disease is another clinical parameter that is useful in
stratifying risk. The presence of a carotid bruit, like male gender
and previous MI, nearly doubles the risk for severe CAD (134).
In addition to peripheral vascular disease, signs and symptoms related
to CHF, which reflect LV function, convey an adverse prognosis.
All
the studies evaluating clinical characteristics as predictors of
severe CAD used only patients referred for further evaluation of
chest pain and cardiac catheterization. Although it does not undercut
internal validity, this bias in the assembly of a cohort severely
limits the generalizability (external validity) of study findings
to all patients with CAD. However, it is likely that the overall
“risk” of an unselected population is lower, so that
patients described as “low risk” by these findings are
still likely to be low risk.
Risk
stratification of patients with stable angina using clinical parameters
may facilitate the development of clearer indications of referral
for exercise testing and cardiac catheterization. Long-term follow-up
data from the CASS registry (352)
showed that 72% of the deaths occurred in the 38% of the population
that had either LV dysfunction or severe coronary disease. The prognosis
of patients with a normal ECG (which implies normal LV function
at rest) and a low clinical risk for severe CAD is therefore excellent.
Pryor et al. (41) showed that 37%
of outpatients referred for noninvasive testing met the criteria
for low risk. Fewer than 1% of these patients had left main artery
disease or died within 3 years. The value of additional testing
for risk stratification in such patients is modest. Lower-cost options
such as treadmill testing should therefore be used whenever possible,
and only the most abnormal results (described in Section III.2)
should be referred to angiography.
B.
Electrocardiogram/Chest X-Ray
Patients
with chronic stable angina who have rest ECG abnormalities are at
greater risk than those with normal ECGs (355).
Evidence of at least 1 prior MI on ECG indicates an increased risk
for cardiac events. In fact, the presence of Q waves in multiple
ECG leads, often accompanied by an R wave in lead V1
(posterior infarction), is frequently associated with a markedly
reduced LV ejection fraction, an important determinant of the natural
history of patients with suspected atherosclerotic CHD (356).
A “QRS score” has been used to indicate the extent of
old or new MI (357), with the higher
scores being associated with lower LV ejection fractions and a poorer
long-term prognosis. The presence of persistent ST-T-wave inversions,
particularly in leads V1 to V3 of the rest
ECG, is associated with an increased likelihood of future acute
coronary events and a poor prognosis (358-361).
A decreased prognosis for patients with angina pectoris is also
likely when the ECG shows left bundle-branch block, bifascicular
block (often left anterior fascicular block plus right bundle-branch
block), second- or third-degree AV block, atrial fibrillation, or
ventricular tachyarrhythmias (362).
The presence of LVH by ECG criteria in a patient with angina pectoris
is also associated with increased morbidity and mortality (361,363).
On
the chest roentgenogram, the presence of cardiomegaly, an LV aneurysm,
or pulmonary venous congestion is associated with a poorer long-term
prognosis than that which occurs in patients with a normal chest
X-ray result. The presence of left atrial enlargement, which indicates
a higher likelihood of pulmonary venous congestion or mitral regurgitation,
is also a negative prognostic factor.
As
indicated previously, the presence of calcium in the coronary arteries
on chest X-ray or fluoroscopy in patients with symptomatic CAD suggests
an increased risk of cardiac events (364).
The presence and amount of coronary artery calcification by EBCT
also correlates to some extent with the severity of CAD, but there
is considerable patient variation.
C.
Noninvasive Testing
1.
Resting LV Function (Echocardiographic/Radionuclide Imaging)
Recommendations
for Measurement of Rest LV Function by Echocardiography or Radionuclide
Angiography in Patients With Chronic Stable Angina
Class
I
1.
Echocardiography or RNA in patients with a history of prior MI,
pathologic Q waves, or symptoms or signs suggestive of heart failure
to assess LV function. (Level of Evidence: B)
2.
Echocardiography in patients with a systolic murmur that suggests
mitral regurgitation to assess its severity and etiology. (Level
of Evidence: C)
3.
Echocardiography or RNA in patients with complex ventricular arrhythmias
to assess LV function. (Level of Evidence: B)
Class
III
1.
Routine periodic reassessment of stable patients for whom no new
change in therapy is contemplated. (Level of Evidence: C)
2.
Patients with a normal ECG, no history of MI, and no symptoms or
signs suggestive of CHF. (Level of Evidence: B)
Importance
of Assessing LV Function
Most
patients undergoing a diagnostic evaluation for angina do not need
an echocardiogram. However, in the chronic stable angina patient
who has a history of documented MI or Q waves on ECG, measurement
of global LV systolic function (e.g., ejection fraction) may be
important in choosing appropriate medical or surgical therapy and
making recommendations about activity level, rehabilitation, and
work status (13,365).
Similarly, cardiac imaging may be helpful in establishing pathophysiologic
mechanisms and guiding therapy in patients who have clinical signs
or symptoms of heart failure in addition to chronic stable angina.
For example, a patient with heart failure might have predominantly
systolic LV dys-function, predominantly diastolic dysfunction, mitral
or aortic valve disease, some combination of these abnormalities,
or a noncardiac cause for symptoms. The best treatment of the patient
can be planned more rationally if the status of LV systolic and
diastolic function (by echocardiography or radionuclide imaging),
valvular function, and pulmonary artery pressure (by echocardiographic
transthoracic echo-Doppler techniques) is known.
Assessment
of Global LV Function
Left
ventricular global systolic function and volumes have been well
documented to be important predictors of prognosis in patients with
cardiac disease. In patients with chronic ischemic heart disease,
LV ejection fraction measured at rest by either echocardiography
(352) or RNA (96,352,365)
is predictive of long-term prognosis; as LV ejection fraction declines,
mortality increases (352). A rest
ejection fraction of less than 35% is associated with an annual
mortality rate greater than 3% per year.
Current
echocardiographic techniques permit a comprehensive assessment of
LV size and function (366,377).
Two dimensional echocardiographic LV ejection fraction may be measured
quantitatively or reported qualitatively (by visual estimation)
as increased; normal; or mildly, moderately, or severely reduced.
When performed by skilled observers, visual estimation has been
reported to yield ejection fractions that correspond closely to
those obtained by angiography (368)
or gated blood pool scanning (369).
In addition to measures of LV systolic function, echo-Doppler characteristics
of the pulsed-Doppler transmitral velocity pattern can help assess
diastolic function (370), although
its independent prognostic value has not been established.
Left
ventricular mass and wall thickness-to-chamber radius ratio, as
measured from echocardiographic images, have both been shown to
be independent of cardiovascular morbidity and mortality (371-373).
The LV mass can be measured from two-dimensional or two-dimensionally
directed M-mode echocardiographic images.
Radionuclide
ejection fraction may be measured at rest with a gamma camera, a
99mTc tracer, and first-pass or gated equilibrium blood pool angiography
(13) or gated SPECT perfusion imaging
(257). Diastolic function can also
be assessed by radionuclide ventriculography (374,375).
It should be noted that LV ejection fraction and other indexes of
myocardial contractile performance are limited by their dependence
on loading conditions and heart rate (146,376).
Although
magnetic resonance imaging is less widely disseminated, it may also
be used to assess LV performance, including ejection fraction (377).
Left
Ventricular Segmental Wall-Motion Abnormalities
In
patients with chronic stable angina and a history of previous MI,
segmental wall-motion abnormalities can be seen not only in the
zone(s) of prior infarction but also in areas with ischemic “stunning”
or “hibernation” of myocardium that is nonfunctional
but still viable (143,148,151,378-380).
The
sum of these segmental abnormalities reflects total ventricular
functional impairment, which may overestimate true anatomic infarct
size or radionuclide perfusion defect (380).
Thus, echocardiographically derived infarct size (143)
correlates only modestly with 201Tl perfusion defects
(151), peak creatine kinase levels
(148,381),
hemodynamic changes (143), and
pathologic findings (379). However,
it does predict the development of early (382)
and late (383) complications and
mortality (143,384).
As
mentioned previously (Sections II.C.3 and II.C.4), recent developments
in both echocardiography (tissue harmonic imaging and intravenous
contrast agents to assess the endocardium) and myocardial perfusion
imaging (gated SPECT imaging to assess global and regional function)
should improve the ability of both techniques to assess LV function.
Ischemic
Mitral Regurgitation, LV Aneurysm, and LV Thrombosis
In
patients with chronic ischemic heart disease, mitral regurgitation
may result from global LV systolic dysfunction (161),
regional papillary muscle dysfunction (162),
scarring and shortening of the submitral chords (163),
papillary muscle rupture (164),
or other causes. The presence, severity, and mechanism of mitral
regurgitation can be reliably detected by transthoracic imaging
and Doppler echocardiographic techniques (13).
Potential surgical approaches also can be defined. In addition,
chronic stable angina patients who have ischemic mitral regurgitation
have a worse prognosis than those without regurgitation.
In
patients with chronic angina and concomitant heart failure or significant
ventricular arrhythmias, the presence or absence of ventricular
aneurysm can generally be established by transthoracic echocardiography
(385,386). When an aneurysm is
demonstrated, the function of the nonaneurysmal portion of the left
ventricle is an important consideration in the choice of medical
or surgical therapy (387). Echocardiography
is the definitive test for detecting intracardiac thrombi (388-394).
The LV thrombi are most common in stable angina pectoris patients
who have significant LV wall-motion abnormalities.
In
patients with anterior and apical infarctions (388,392-394),
the presence of LV thrombi denotes an increased risk of both embolism
(389) and death (391).
In addition, the structural appearance of a thrombus, which can
be defined by transthoracic (or transesophageal) echocardiography,
has some prognostic significance. Sessile, laminar thrombi represent
less of a potential embolic risk than do pedunculated and mobile
thrombi (13).
Asymptomatic
Patients
In
asymptomatic patients with a history of documented MI or Q waves
on ECG, measurement of global LV systolic function is important.
The recommendations listed earlier in this section for symptomatic
patients are applicable. Echocardiography or RNA may help to confirm
the history or ECG evidence of prior infarction by the demonstration
of global or regional dysfunction. A decreased ejection fraction
is prognostically important even in the absence of symptoms. Therapy
with an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker
may then be appropriate. This issue is addressed in detail in the
“ACC/AHA Guidelines for the Evaluation and Management of Chronic
Heart Failure in the Adult” (897).
2.
Exercise Testing for Risk Stratification and Prognosis
Recommendations
for Risk Assessment and Prognosis in Patients With an Intermediate
or High Probability of CAD
Class
I
1.
Patients undergoing initial evaluation. (Exceptions are listed below
in Classes IIb and III) (Level of Evidence: B)
2.
Patients after a significant change in cardiac symptoms. (Level
of Evidence: C)
Class
IIb
1.
Patients with the following ECG abnormalities:
a.
Pre-excitation (Wolff-Parkinson-White) syndrome. (Level of Evidence:
B)
b.
Electronically paced ventricular rhythm. (Level of Evidence:
B)
c.
More than 1 mm of ST depression at rest. (Level of Evidence:
B)
d.
Complete left bundle-branch block. (Level of Evidence: B)
2.
Patients who have undergone cardiac catheterization to identify
ischemia in the distribution of coronary lesion of borderline severity.
(Level of Evidence: C)
3.
Postrevascularization patients who have a significant change in
anginal pattern suggestive of ischemia. (Level of Evidence:
C)
Class
III
Patients
with severe comorbidity likely to limit life expectancy or prevent
revascularization. (Level of Evidence: C)
Risk
Stratification for Death or MI: General Considerations
Risk
stratification with the exercise test does not take place in isolation
but as part of a process that includes other data from the clinical
examination and other laboratory tests. Thus, the value of exercise
testing for risk stratification must be considered in light of what
is added to what is already known about the patient’s risk
status. Most research on exercise testing has concentrated on its
relationship with future survival and, to a lesser extent, freedom
from MI. The summary presented here is based on the “ACC/AHA
2002 Guideline Update for Exercise Testing”
(14,894).
Risk
Stratification With the Exercise Test
The
risk of exercise testing in appropriately selected candidates is
extremely low, and thus the main argument for not performing an
exercise test is that the extra information provided would not be
worth the extra cost of obtaining that information, or that the
test might provide misinformation that could lead to inappropriate
testing or therapy.
Unless
cardiac catheterization is indicated, symptomatic patients with
suspected or known CAD should usually undergo exercise testing to
assess the risk of future cardiac events unless they have confounding
features on the rest ECG. Furthermore, documentation of exercise-induced
ischemia is desirable for most patients who are being evaluated
for revascularization (72,395).
The
choice of initial stress test should be based on the patient’s
rest ECG, physical ability to perform exercise, local expertise,
and available technologies. Patients with a normal rest ECG constitute
a large and important subgroup. Most patients who present with angina
for the first time have a normal rest ECG (49).
Such patients are very likely (92% to 96%) to have normal LV function
(141,142,396)
and therefore an excellent prognosis (49).
The exercise ECG has a higher specificity in the absence of rest
ST-T changes, LVH, and digoxin.
Several
studies have examined the incremental value of exercise imaging
procedures compared with the exercise ECG in patients with a normal
rest ECG who are not taking digoxin (Table
19). In analyses (397,398)
that included clinical and exercise ECG parameters for the prediction
of left main or three-vessel disease, the modest benefit of imaging
does not appear to justify its cost, which has been estimated at
$20 550 per additional patient correctly classified (397).
For the prediction of subsequent cardiac events, four separate analyses
have failed to demonstrate incremental value. Mattera et al. (399)
did find some incremental value, but only for the prediction of
hard and soft events (including unstable angina) and only if the
exercise ECG was abnormal. They still favored a stepwise strategy
that used the exercise ECG as the initial test, like that proposed
by others (83,400).
For
these reasons, the committee favored a stepwise strategy in which
the exercise ECG, and not stress imaging procedures, is performed
as the initial test in patients who are not taking digoxin, have
a normal rest ECG, and are able to exercise. In contrast, a stress-imaging
technique should be used for patients with widespread rest ST depression
(greater than 1 mm), complete left bundle-branch block, ventricular
paced rhythm, or pre-excitation. Although exercise capacity can
be assessed in such patients, exercise-induced ischemia cannot.
Patients unable to exercise because of physical limitations such
as reduced exercise capacity, arthritis, amputations, severe peripheral
vascular disease, or severe chronic obstructive pulmonary disease
should undergo pharmacologic stress testing in combination with
imaging.
The
primary evidence that exercise testing can be used to estimate prognosis
and assist in management decisions consists of seven observational
studies (354,355,401-405).
One of the strongest and most consistent prognostic markers is maximum
exercise capacity. This measure is at least partly influenced by
the extent of rest LV dysfunction and the amount of further LV dysfunction
induced by exercise. However, the relationship between exercise
capacity and LV function is complex, because exercise capacity is
also affected by age, general physical conditioning, comorbidities,
and psychological state, especially depression (406).
Exercise capacity is measured by maximum exercise duration, maximum
MET level achieved, maximum workload achieved, maximum heart rate,
and double product. The specific variable used to measure exercise
capacity is less important than the inclusion of exercise capacity
in the assessment. The translation of exercise duration or workload
into METs provides a standard measure of performance regardless
of the type of exercise test or protocol used.
A
second group of prognostic markers is related to exercise-induced
ischemia. ST-segment depression and elevation (in leads without
pathological Q waves and not in aVR) best summarize the prognostic
information related to ischemia (401).
Other variables are less powerful, including angina, the number
of leads with ST-segment depression, the configuration of the ST
depression (downsloping, horizontal, or upsloping), and the duration
of ST deviation into the recovery phase.
The
Duke treadmill score combines this information and provides a way
to calculate risk (37,401).
The Duke treadmill score equals the exercise time in minutes minus
(5 times the ST-segment deviation, during or after exercise, in
millimeters) minus (4 times the angina index, which has a value
of “0” if there is no angina, “1” if angina
occurs, and “2” if angina is the reason for stopping
the test). Among outpatients with suspected CAD, the two thirds
of patients with scores indicating low risk had a four-year survival
rate of 99% (average annual mortality rate 0.25%), and the 4% who
had scores indicating high risk had a four-year survival rate of
79% (average annual mortality rate 5%; see Table
20). The score works well for both inpatients and outpatients,
and preliminary data suggest that the score works equally well for
men and women (37,409,410).
Only a small number of elderly patients have been studied, however.
Comparable scores have been developed by others (402).
Several
studies have highlighted the prognostic performance of other parameters
from the exercise test: chronotropic incompetence (898,899),
abnormal heart rate recovery (900-905),
and delayed systolic blood pressure response (906).
As indicated in the 2002 update of the ACC/AHA Guidelines for Exercise
Testing (907), further work is
needed to define their role in the risk stratification of symptomatic
patients relative to other well-validated treadmill test parameters.
Because
of its simplicity, lower cost, and widespread familiarity with its
performance and interpretation, the standard exercise test is the
most reasonable one to select for men with a normal rest ECG who
are able to exercise. The optimal testing strategy remains less
well defined in women. Until adequate data are available to resolve
this issue, it is reasonable to use exercise testing for risk stratification
in women.
Use
of Exercise Test Results in Patient Management
The
results of exercise testing may be used to titrate medical therapy
to the desired level of effectiveness. For example, a normal heart
rate response to exercise suggests that the dose of beta-blocker
should be increased. Testing for this purpose should generally be
performed with the patient on medication. The other major management
step addressed by the exercise test is whether to proceed with additional
testing, which might lead to revascularization.
Proceeding
with additional testing usually involves imaging. Although both
stress echocardiography and stress SPECT perfusion imaging have
been used after exercise testing, only SPECT perfusion imaging has
been studied in patients divided into risk groups based on the Duke
treadmill score (410). In patients
with an intermediate-risk treadmill score, imaging appears to be
useful for further risk stratification. In patients with a high-risk
treadmill score, imaging may identify enough low-risk patients who
can avoid cardiac catheterization to justify the cost of routine
imaging, but further study is required. Few patients (less than
5%) who have a low-risk treadmill score will be identified as high
risk after imaging, and thus the cost of identifying these patients
argues against routine imaging (410).
Patients
with a predicted average annual cardiac mortality rate of less than
or equal to 1% per year (low-risk score) can be managed medically
without the need for cardiac catheterization. Patients with a predicted
average annual cardiac mortality rate greater than or equal to 3%
per year (high-risk score) should be referred for cardiac catheterization.
Patients with a predicted average annual cardiac mortality rate
of 1% to 3% per year (intermediate-risk score) should have either
cardiac catheterization or an exercise imaging study. Those with
known LV dysfunction should have cardiac catheterization.
Recommendation
for Exercise Testing in Patients With Chest Pain 6 Months or More
After Revascularization
Class
IIb
Patients
with a significant change in anginal pattern suggestive of ischemia.
(Level of Evidence: B)
RATIONALE.
There are two postrevascularization phases. In the early phase,
the goal of exercise testing is to determine the immediate result
of revascularization. In the late phase, which begins 6 months after
revascularization and is the focus of this discussion, the goal
is to assist in the evaluation and management of patients with chronic
established CAD. Exercise testing also may be helpful in guiding
a cardiac rehabilitation program and return-to-work decisions.
Exercise
Testing After CABG
Exercise
testing distinguishes cardiac from noncardiac causes of chest pain,
which is often atypical after surgery. After CABG, the exercise
ECG has a number of limitations. Rest ECG abnormalities are frequent,
and if an imaging test is not incorporated into the study, more
attention must be paid to symptom status, hemodynamic response,
and exercise capacity. Because of these considerations and the need
to document the site of ischemia, stress imaging tests are preferred
for evaluating patients in this group.
Exercise
Testing After PCI
Similar
considerations apply to angioplasty patients. Restenosis is more
frequent, however. Although most restenosis occurs less than 6 months
after angioplasty, a period when these recommendations do not apply,
restenosis does occur later. The exercise ECG is an insensitive
predictor of restenosis, with sensitivities ranging from 40% to
55%, significantly less than those with SPECT (12,411)
or exercise echocardiography (13,412).
Because of these considerations and the need to document the site
of ischemia, stress imaging tests are preferred for evaluating symptomatic
patients in this group.
Some
authorities advocate routine testing for all patients in the late
phase after PCI with either exercise ECGs or stress imaging, because
restenosis commonly induces silent ischemia. The rationale for this
approach is that ischemia, whether painful or silent, worsens prognosis
(413,414). This approach appears
particularly attractive for high-risk patients, for example, those
with decreased LV function, multivessel CAD, proximal left anterior
descending artery disease, previous sudden death, diabetes mellitus,
hazardous occupations, or suboptimal PCI results. If routine testing
is done, there are insufficient data to justify a particular frequency
of testing after angioplasty. The alternative approach, which the
committee labeled Class IIb because the prognostic benefit of controlling
silent ischemia needs to be proved, is to selectively evaluate only
patients with a significant change in anginal pattern.
Recommendations
for Exercise Testing for Risk Assessment and Prognosis in Asymptomatic
Patients
Class
IIb
Asymptomatic
patients with possible myocardial ischemia on ambulatory ECG monitoring
or with severe coronary calcification on EBCT (exceptions are listed
below in III). (Level of Evidence: C)
Class
III
1.
Asymptomatic patients with possible myocardial ischemia on ambulatory
ECG monitoring or with severe coronary calcification on EBCT, but
with the following baseline ECG abnormalities:
a.
Pre-excitation (Wolff-Parkinson-White) syndrome. (Level of Evidence:
B)
b.
Electronically paced ventricular rhythm. (Level of Evidence: B)
c.
More than 1 mm of ST depression at rest. (Level of Evidence: B)
d.
Complete left bundle-branch block. (Level of Evidence: B)
In
asymptomatic patients with known or suspected CAD on the basis of
possible myocardial ischemia on ambulatory ECG monitoring, severe
coronary calcification on EBCT, or an established diagnosis of CAD
because of prior MI or coronary angiography, risk stratification
and prognosis are more important considerations than diagnosis.
Because the treatment of asymptomatic patients cannot improve their
symptoms, the principal goal of evaluation and treatment is the
improvement of patient outcome by reducing the rate of death and
nonfatal MI. In one large study dominated by asymptomatic patients,
the Duke treadmill score predicted subsequent cardiac events . However,
the absolute event rate was low, even in patients with high-risk
scores, which suggests that the ability to improve outcome with
revascularization in such patients is limited. Asymptomatic patients
with intermediate-risk or high-risk Duke treadmill scores may be
candidates for more intensive risk factor reduction. Patients with
low-risk Duke treadmill scores can clearly be reassured regarding
their low risk for subsequent cardiac events.
3.
Stress Imaging Studies (Radionuclide and Echocardiography)
Recommendations
for Cardiac Stress Imaging as the Initial Test for Risk Stratification
of Patients With Chronic Stable Angina Who Are Able to Exercise
Class
I
1.
Exercise myocardial perfusion imaging or exercise echocardiography
to identify the extent, severity, and location of ischemia in patients
who do not have left bundle-branch block or an electronically paced
ventricular rhythm and who either have an abnormal rest ECG or are
using digoxin. (Level of Evidence: B)
2.
Dipyridamole or adenosine myocardial perfusion imaging in patients
with left bundle-branch block or electronically paced ventricular
rhythm. (Level of Evidence: B)
3.
Exercise myocardial perfusion imaging or exercise echocardiography
to assess the functional significance of coronary lesions (if not
already known) in planning PCI. (Level of Evidence: B)
Class
IIb
1.
Exercise or dobutamine echocardiography in patients with left bundle-branch
block. (Level of Evidence: C)
2.
Exercise, dipyridamole, or adenosine myocardial perfusion imaging,
or exercise or dobutamine echocardiography as the initial test in
patients who have a normal rest ECG and who are not taking digoxin.
(Level of Evidence: B)
Class
III
1.
Exercise myocardial perfusion imaging in patients with left bundle-branch
block. (Level of Evidence: C)
2.
Exercise, dipyridamole, or adenosine myocardial perfusion imaging,
or exercise or dobutamine echocardiography in patients with severe
comorbidity likely to limit life expectation or prevent revascularization.
(Level of Evidence: C)
Recommendations
for Cardiac Stress Imaging as the Initial Test for Risk Stratification
of Patients With Chronic Stable Angina Who Are Unable to Exercise
Class
I
1.
Dipyridamole or adenosine myocardial perfusion imaging or dobutamine
echocardiography to identify the extent, severity, and location
of ischemia in patients who do not have left bundle-branch block
or electronically paced ventricular rhythm. (Level of Evidence:
B)
2.
Dipyridamole or adenosine myocardial perfusion imaging in patients
with left bundle-branch block or electronically paced ventricular
rhythm. (Level of Evidence: B)
3.
Dipyridamole or adenosine myocardial perfusion imaging or dobutamine
echocardiography to assess the functional significance of coronary
lesions (if not already known) in planning PCI. (Level of Evidence:
B)
Class
IIb
Dobutamine
echocardiography in patients with left bundle-branch block. (Level
of Evidence: C)
Class
III
Dipyridamole
or adenosine myocardial perfusion imaging or dobutamine echocardiography
in patients with severe comorbidity likely to limit life expectation
or prevent revascularization. (Level of Evidence: C)
Available
Stress Imaging Approaches
Stress
imaging studies with radionuclide myocardial perfusion imaging techniques
or two-dimensional echocardiogra phy at rest and during stress are
useful for risk stratification and determination of the most beneficial
management strategy for patients with chronic stable angina (415-417).
Whenever possible, treadmill or bicycle exercise should be used
as the most appropriate form of stress, because it provides the
most information concerning patient symptoms, cardiovascular function,
and hemodynamic response during usual forms of activity (14,894).
In fact, the inability to perform a bicycle or exercise treadmill
test is in itself a negative prognostic factor for patients with
chronic CAD.
In
patients who cannot perform an adequate amount of bicycle or treadmill
exercise, various types of pharmacologic stress are useful for risk
stratification (12,13,217,418).
The selection of the type of pharmacologic stress will depend on
specific patient factors, such as the patient’s heart rate
and blood pressure, the presence or absence of bronchospastic disease,
the presence of left bundle-branch block or a pacemaker, and the
likelihood of ventricular arrhythmias.
Pharmacologic
agents are often used to increase cardiac workload as a substitute
for treadmill or bicycle exercise or to cause an increase in overall
coronary blood flow (224,225).
For the former effect, adrenergic-stimulating drugs (such as dobutamine
or arbutamine) are usually used, and for the latter effect, vasodilating
agents (such as dipyridamole or adenosine) are generally used (12,13,217,224,225,418)
(see Section II.C.4).
Radionuclide
imaging has played a major role in risk stratification of patients
with CAD. Either planar (three conventional views) or SPECT (multiple
tomographic slices in three planes) imaging with 201Tl or 99mTc
perfusion tracers with images obtained at stress and during rest
provide important information about the severity of functionally
significant CAD (180-188,191,192,199,204,205,419).
More
recently, stress echocardiography has been used to assess patients
with chronic stable angina; thus, the amount of prognostic data
obtained with this approach is somewhat limited. Nevertheless, the
presence or absence of inducible myocardial wall-motion abnormalities
has useful predictive value in patients undergoing exercise or pharmacologic
stress echocardiography. A negative stress echocardiography study
denotes a low cardiovascular event rate during followup (420-428).
Important
Findings on Stress Perfusion Studies for Risk Stratification
Normal
poststress thallium scan results are highly predictive of a benign
prognosis even in patients with known coronary disease (12).
A collation of 16 studies involving 3594 patients followed up for
a mean of 29 months indicated a rate of cardiac death and MI of
0.9% per year (429), nearly as
low as that of the general population (430).
In a recent prospective study of 5183 consecutive patients who underwent
myocardial perfusion studies during stress and later at rest, patients
with normal scans were at low risk (less than 0.5% per year) for
cardiac death and MI during 642 (plus or minus 226) days of mean
follow-up, and rates of both outcomes increased significantly with
worsening scan abnormalities (431).
The presence of a normal stress myocardial perfusion scan indicates
such a low likelihood of significant CAD that coronary arteriography
is usually not indicated as a subsequent test. Although the published
data are limited, the single exception would appear to be patients
with high-risk treadmill scores and normal images (431).
The
number, extent, and site of abnormalities on stress myocardial perfusion
scintigrams reflect the location and severity of functionally significant
coronary artery stenoses. Lung uptake of 201Tl on postexercise or
pharmacologic stress images is an indicator of stress-induced global
LV dysfunction and is associated with pulmonary venous hypertension
in the presence of multivessel CAD (432-435).
Transient poststress ischemic LV dilation also correlates with severe
two- or three-vessel CAD (436-439).
Several studies have suggested that SPECT may be more accurate than
planar imaging for determining the size of defects, detecting coronary
and particularly left circumflex CAD, and localizing abnormalities
in the distribution of individual coronary arteries (180,204,419).
However, more false-positive results are likely to result from photon
attenuation during SPECT imaging (12).
The
number, size, and location of perfusion abnormalities; the amount
of lung uptake of 201Tl on poststress images; and the presence or
absence of poststress ischemic LV dilation can be combined to maximize
the recognition of high-risk patients, including those with multivessel
disease, left main CAD, and disease of the proximal portion of the
left anterior descending coronary artery (LAD). Incremental prognostic
information from the results of stress myocardial perfusion imaging
can determine the likelihood of subsequent important cardiac events.
The number of transient perfusion defects, whether provoked by exercise
or pharmacologic stress, is a reliable predictor of subsequent cardiac
death or nonfatal MI (180,419,440-447).
The number of stenotic coronary arteries may be less predictive
than the number of reversible perfusion defects (440-450).
The magnitude of the perfusion abnormality was the single most prognostic
indicator in a study that demonstrated independent and incremental
prognostic information from SPECT 201Tl scintigraphy compared with
that obtained from clinical, exercise treadmill, and catheterization
data (451). As indicated previously,
increased lung uptake of thallium induced by exercise or pharmacologic
stress is associated with a high risk for cardiac events (12,452).
Information
concerning both myocardial perfusion and ventricular function at
rest may be helpful in determining the extent and severity of coronary
disease (181,183,453).
This combined information can be obtained by performing two separate
exercise tests (e.g., stress perfusion scintigraphy and stress RNA)
or combining the studies after one exercise test (e.g., first-pass
RNA with 99mTc-based agents followed by perfusion imaging or perfusion
imaging with gating). However, an additional benefit of the greater
information provided by combined myocardial perfusion and ventricular
function exercise testing has not been shown in clinical outcome
or prognostic studies (12). Thus,
one determination of LV function at rest and one measure of exercise/pharmacologic
stress-induced myocardial perfusion or exercise ventricular function,
but not both, are appropriate (12).
The prognostic value of stress myocardial perfusion imaging in chronic
stable angina is summarized in Table 21
(studies with greater than 100 patients who did not have recent
MI and that included both positive and negative perfusion images).
Application
of Myocardial Perfusion Imaging to Specific Patient Subsets
PATIENTS
WITH A NORMAL REST ECG. Myocardial perfusion imaging has little
advantage over the less expensive treadmill exercise test in this
subset of patients. Three separate studies (402,404,405)
have demonstrated little if any incremental value of myocardial
perfusion imaging in the initial evaluation of such patients. As
mentioned previously (Section III.2), many such patients will have
low-risk treadmill scores and will not require further evaluation.
CONCOMITANT
USE OF DRUGS. As mentioned previously (Sections II.2 and II.4),
beta-blockers (and other antiischemic drugs) should be withheld
for four to five half-lives before testing. However, even if these
drugs are continued, most high-risk patients will usually still
be identified (14,894).
Nitrates may also decrease the extent of perfusion defects or even
convert abnormal exercise scan results to normal results (462).
WOMEN,
THE ELDERLY, OR OBESE PATIENTS. The treadmill ECG test is less accurate
for the diagnosis of CHD in women, who have a lower pretest likelihood
than men (194). However, the sensitivity
of thallium perfusion scans may be lower in women than in men (194,245).
Artifacts due to breast attenuation, usually manifest in the anterior
wall, can be an important consideration in the interpretation of
women’s scans, especially when 201Tl is used as a tracer (12).
As mentioned previously, 99mTc sestamibi may be preferable to 201Tl
scintigraphy for determining prognosis and diagnosing CAD in women
with large breasts or breast implants (248).
Although
many elderly patients can perform an exercise test, some are unable
to do so because of physical impairment. Pharmacologic stress imaging
is an appropriate option for risk stratification in such patients.
Very obese patients constitute a specific problem because most imaging
tables used for SPECT have weight-bearing limits (usually 300 to
450 lb) that preclude imaging very heavy subjects. These subjects
can still be imaged by planar scintigraphy (12).
Obese patients often have suboptimal perfusion images, especially
with 201Tl because of the marked photon attenuation by soft tissue.
In these patients, 99mTc sestamibi is probably the most appropriate
and should provide images of better quality than 201Tl.
LEFT
BUNDLE-BRANCH BLOCK. As mentioned previously (Section II.4), pharmacologic
stress perfusion imaging is preferable to exercise perfusion imaging
in patients with left bundle-branch block. Recently, 245 patients
with left bundle-branch block underwent SPECT imaging with 201Tl
(n = 173) or 99mTc sestamibi (n = 72) during dipyridamole (n = 153)
or adenosine (n = 92) stress testing (463).
Patients with a large, severe fixed defect, a large reversible defect,
or cardiac enlargement and either increased pulmonary uptake (thallium)
or decreased ejection fraction (sestamibi) were classified as high-risk
patients (n = 20). The rest were classified as low risk. The three-year
overall survival rate was 57% in the high-risk group compared with
87% in the low-risk group (p = 0.001). Patients with a low-risk
scan had an overall survival rate that was not significantly different
from that of the U.S.-matched population (p = 0.86). The value of
pharmacologic perfusion imaging for prognostication was confirmed
in three other studies (464-466)
that included more than 300 patients followed up for a mean of nearly
three years. Normal dipyridamole or adenosine scans were associated
with a low cardiac event rate; large defects and increased pulmonary
uptake were associated with a high cardiac event rate.
AFTER
CORONARY ANGIOGRAPHY. Myocardial perfusion imaging is useful in
planning revascularization procedures because it demonstrates whether
a specific coronary stenosis is associated with the stress-induced
perfusion abnormality (12). Myocardial
perfusion imaging is particularly helpful in determining the functional
importance of single or multiple stenoses when PCI is targeted to
the “culprit lesion,” that is, the ischemia-provoking
stenosis (12,463,467-469).
AFTER
MYOCARDIAL REVASCULARIZATION. Myocardial perfusion imaging can be
useful in several situations after coronary bypass surgery. In patients
with ST-T-wave abnormalities at rest, recurrent myocardial ischemia
during stress can be better evaluated by exercise scintigraphy than
ECG treadmill testing. In addition, approximately 30% have an abnormal
ECG response on treadmill exercise testing early after bypass surgery
(470); these patients can be assessed
for potential and incomplete revascularization and the extent of
myocardium affected. Patients with initial negative postoperative
treadmill test results that later become positive usually have progressive
ischemia due to either graft closure or progression of disease in
the native circulation (471). Myocardial
perfusion scintigraphy can be useful in determining the location,
extent, and severity of such ischemia (12).
Its prognostic value has been demonstrated both early (472)
and late (473-475) after CABG.
AFTER
EXERCISE TESTING. In patients who perform a treadmill exercise test
that is not associated with an adequate exercise effort necessary
to risk stratify the patient appropriately, a repeat exercise test
with thallium scintigraphy or a myocardial perfusion imaging test
with pharmacologic stress may give a better indication of the presence
or absence of highrisk coronary disease (14,894).
Important
Findings on Stress Echocardiography for Risk Stratification
Stress
echocardiography is both sensitive and specific for detecting inducible
myocardial ischemia in patients with chronic stable angina (13)
(see Section II.C.4). Compared with standard exercise treadmill
testing, stress echocardiography provides an additional clinical
value for detecting and localizing myocardial ischemia. The results
of stress echocardiography may provide important prognostic value.
Several studies indicate that patients at low, intermediate, and
high risk for cardiac events can be stratified on the presence or
absence of inducible wall-motion abnormalities on stress echocardiography
testing. A positive stress echocardiographic study can be useful
in determining the location and severity of inducible ischemia,
even in a patient with a high pretest likelihood that disease is
present. A negative stress echocardiographic evaluation predicts
a low risk for future cardiovascular events (420-428).
However,
the value of a negative study compared with a negative thallium
study must be further documented, because there are fewer follow-up
data than with radionuclide imaging. Recently, McCully et al. (476)
assessed the outcomes of 1325 patients who had normal exercise echocardiograms
with overall and cardiac event-free survival as end points. Cardiac
events included cardiac death, nonfatal MI, and coronary revascularization.
The event-free survival rates were 99.2% at one year, 97.8% at two
years, and 97.4% at three years. Table 22
summarizes the prognostic value of stress echocardiography from
the literature (studies with more than 100 patients who did not
have recent MI and that included both positive and negative echocardiograms).
The presence of ischemia on the exercise echocardiogram is inde
pendent and incremental to clinical and exercise data in predicting
cardiac events in both men and women (477,478).
The prognosis is not benign in patients with a positive stress echocardiographic
study. In this subset, morbid or fatal cardiovascular events are
more likely, but the overall event rates are rather variable. Hence,
the cost-effectiveness of using routine stress echocardiographic
testing to establish prognosis is uncertain.
In
general, patients with a positive ECG response to treadmill stress
testing but no inducible wall-motion abnormality on stress echocardiography
have a very low rate of adverse cardiovascular events during follow-up
(13,420,421),
albeit higher than in patients with negative ECG results as well.
However, the number of patients followed up after both stress ECG
and stress echocardiography is relatively small, and there has been
no breakdown into groups with various METs achieved during ECG treadmill
testing and with different risks according to the treadmill score
(see Section II.C.2).
In
patients with a significant clinical suspicion of CAD, stress echocardiography
is appropriate for risk stratification when standard exercise testing
is likely to be suboptimal (14,894).
A variety of methods can be used to induce stress. Treadmill stress
echocardiography may have lowered sensitivity if there is a significant
delay from the end of exercise to the acquisition of postexercise
images. Dobutamine stress echocardiography has substantially higher
sensitivity than vasodilator stress echocardiography for detecting
coronary stenoses (13,224,225,479).
Sensitivity can also be diminished if all myocardial segments are
not adequately visualized.
Application
of Stress Echocardiography to Specific Patient Subsets
WOMEN,
THE ELDERLY, AND OBESE PATIENTS. There are some recent data concerning
the usefulness of stress echocardiography in women compared with
men. Two studies by Marwick and associates (129,479)
define the predictive value of exercise echocardiography as an independent
predictor of cardiac events in women with known or suspected CAD.
Symptom-limited exercise echocardiography was performed in 508 consecutive
women (aged 55 plus or minus 10 years) between 1989 and 1993 (129),
with a follow-up of 41 (plus or minus 10) months. Cardiac events
occurred in 7% of women, and exercise echocardiography provided
key prognostic information incremental to clinical and exercise
testing data with a Cox proportional hazard model. In another group
of women, the specificity of exercise echocardiography for indicating
CAD and potential risk exceeded that of exercise electrocardiography
(80% plus or minus 3% vs. 64% plus or minus 3%, p = 0.05) and was
a more cost-effective approach (129).
Although these data are promising, the committee thought that in
most women, ECG treadmill testing should still be the first choice
for detecting high-risk inducible myocardial ischemia.
The
echocardiographic window and the number of myocardial segments detected
during exercise or dobutamine echocardiography are often suboptimal
in very obese patients and many elderly patients who have chronic
obstructive lung disease and a suboptimal echocardiographic window.
As mentioned previously (Section II.C.3), tissue harmonic imaging
and contrast echocardiography should improve detection of the endocardium.
LEFT
BUNDLE-BRANCH BLOCK. Like exercise myocardial perfusion imaging
studies, the significance of stress-induced echocardiography wall-motion
abnormalities in patients with left bundle-branch block is unreliable
(13). During either exercise or
dobutamine stimulation, abnormal contraction of the intraventricular
septum has been a frequent occurrence in patients with left bundle-branch
block who do not have underlying disease of the LAD.
AFTER
CORONARY ANGIOGRAPHY. Echocardiographic studies may help in planning
revascularization procedures by demonstrating the functional significance
of a given coronary stenosis. This may be of particular value in
determining the need for PCI, especially when the degree of angiographic
stenosis is of uncertain physiologic significance or when multiple
lesions are present (13).
AFTER
REVASCULARIZATION. When symptoms persist or recur six months or
more after CABG, echocardiographic testing can be useful. Abnormal
baseline ECG findings after cardiac surgery are common, and postbypass
patients frequently have abnormal ECG responses on standard treadmill
testing. When symptoms of ischemia suggest incomplete revascularization,
stress echocardiography studies may demonstrate the location and
severity of residual ischemia. When symptoms recur after initial
relief and the stress echocardiogram demonstrates inducible ischemia,
either graft closure or the development of new coronary artery obstructive
lesions is likely (482).
AFTER
TREADMILL EXERCISE TESTING. As with stress myocardial perfusion
imaging, stress echocardiography may provide additional information
in patients unable to perform appropriate exercise on the treadmill
and in those who have an intermediate risk determined by ECG criteria
during exercise testing (13).
ASYMPTOMATIC
PATIENTS
Recommendations
for Cardiac Stress Imaging as the Initial Test for Risk Stratification
in Asymptomatic Patients
Class
IIb
1.
Exercise perfusion imaging or exercise echocardiography in asymptomatic
patients with severe coronary calcification on EBCT who are able
to exercise and have one of the following baseline ECG abnormalities:
a.
Pre-excitation (Wolff-Parkinson-White) syndrome. (Level of Evidence:
C)
b.
More than 1 mm of ST depression at rest. (Level of Evidence:
C)
2.
Adenosine or dipyridamole myocardial perfusion imaging in patients
with severe coronary calcification on EBCT, but with one of the
following baseline ECG abnormalities:
a.
Electronically paced ventricular rhythm. (Level of Evidence:
C)
b.
Left bundle-branch block. (Level of Evidence: C)
3.
Adenosine or dipyridamole myocardial perfusion imaging or dobutamine
echocardiography in patients with possible myocardial ischemia on
ambulatory ECG monitoring or with severe coronary calcification
on EBCT who are unable to exercise. (Level of Evidence: C)
Class
III
1.
Exercise or dobutamine echocardiography in asymptomatic patients
with left bundle-branch block. (Level of Evidence: C)
2.
Exercise myocardial perfusion imaging, exercise echocardiography,
adenosine or dipyridamole myocardial perfusion imaging, or dobutamine
echocardiography as the initial stress test in an asymptomatic patient
with a normal rest ECG who is not taking digoxin. (Level of
Evidence: C)
3.
Adenosine or dipyridamole myocardial perfusion imaging or dobutamine
echocardiography in asymptomatic patients who are able to exercise.
(Level of Evidence: C)
Recommendations
for Cardiac Stress Imaging After Exercise ECG Testing for Risk Stratification
in Asymptomatic Patients
Class
IIb
1.
Exercise myocardial perfusion imaging or exercise echocardiography
in asymptomatic patients with an intermediate-risk or high-risk
Duke treadmill score on exercise ECG testing. (Level of Evidence:
C)
2.
Adenosine or dipyridamole myocardial perfusion imaging or dobutamine
echocardiography in asymptomatic patients with a previously inadequate
exercise ECG. (Level of Evidence: C)
Class
III
Exercise
myocardial perfusion imaging, exercise echocardiography, adenosine
or dipyridamole myocardial perfusion imaging, or dobutamine echocardiography
in asymptomatic patients with a low-risk Duke treadmill score on
exercise ECG testing. (Level of Evidence: C)
As
already discussed in Section III.C.2, asymptomatic patients who
are able to exercise can usually be evaluated with exercise ECG
testing. Stress imaging procedures should be reserved for patients
with resting ECG abnormalities and severe coronary calcification
on EBCT, patients who are unable to exercise, and as a second test
for patients with an intermediate-risk or high-risk Duke treadmill
score on initial exercise ECG testing. Published data demonstrating
the efficacy of stress imaging procedures in these specific circumstances
are scant. Some of the published series listed in Tables 21 and
22 did include asymptomatic patients. However, this subset of patients
was generally not analyzed separately. Blumenthal et al. reported
a small study using exercise thallium testing in siblings of patients
with premature coronary atherosclerosis (814).
They demonstrated that the combination of an abnormal exercise ECG
and a positive thallium image was prognostically important. However,
many of the events included in their analysis were subsequent revascularizations,
the performance of which was clearly influenced by the results of
the exercise thallium test. Given the generally low event rate in
asymptomatic patients, the ability of stress imaging procedures
to identify a subset with a substantial absolute risk of subsequent
events is problematic, with the possible exception of patients with
previous MI.
D.
Coronary Angiography and Left Ventriculography
The
availability of potent but expensive strategies to reduce the long-term
risk of CAD mandates that the patients most likely to benefit, namely,
those at increased risk, be identified. This effort poses a significant
challenge to both the cardiovascular specialist and primary-care
physician (41,134,333,483-486).
It is important to recognize that the science of risk prediction
is only now evolving, and in the case of coronary atherosclerosis,
methods of identifying vulnerable plaques, the precursors of coronary
events, are lacking (41,134,333,485-487).
Assessment
of cardiac risk and decisions regarding further testing usually
begin with simple, repeatable, and inexpensive assessments of history
and physical examination and extend to noninvasive or invasive testing,
depending on outcome. Clinical risk factors are in general additive,
and a crude estimate of one-year mortality can be obtained from
these variables. An index has been developed that is the sum of
the age plus a score based on symptoms plus comorbidity (diabetes,
peripheral vascular disease, cerebrovascular disease, prior MI)
(485). It is important to note
that one-year mortality rates of patients without severe comorbidity
who have stable, progressive, and unstable angina are similar (range
1.3% to 1.7%), which shows the limited predictive value of symptom
severity alone (485). Patients
with mild anginal symptoms may have severe coronary disease (41,333,485),
which is detectable only with noninvasive or invasive testing. LV
dysfunction is a powerful determinant of long-term survival in patients
with chronic stable angina pectoris (94,488).
It may be inferred from extensive Q-wave formation on ECG or history
of CHF or measured noninvasively by echocardiography, radionuclide
techniques, or contrast angiography at the time of coronary angiography.
The coexistence of significant LV dysfunction and chronic stable
angina constitutes increased risk and warrants careful further evaluation.
Risk
stratification of patients with chronic stable angina by stress
testing with exercise or pharmacologic agents has been shown to
permit identification of groups of patients with low, intermediate,
or high risk of subsequent cardiac events (12,13,14,37,894)
(see Sections III.B and III.C). Although one recent study (431)
suggested that myocardial perfusion imaging can identify patients
who are at low risk of death but increased risk of nonfatal MI,
the major current focus of noninvasive risk stratification is on
subsequent patient mortality. The rationale is to identify patients
in whom coronary angiography and subsequent revascularization might
improve survival. Such a strategy can be effective only if the patient’s
prognosis with medical therapy is sufficiently poor that it can
be improved.
Previous
experience in the randomized trials of CABG demonstrated that patients
randomized to initial CABG had a lower mortality rate than those
treated with medical therapy only if they were at substantial risk
(489). Low-risk patients who did
not have a lower mortality rate with CABG had a five-year survival
rate of about 95% with medical therapy. This is equivalent to an
annual mortality rate of 1%. As a result, coronary angiography to
identify patients whose prognosis can be improved is inappropriate
when the estimated annual mortality rate is less than or equal to
1%. In contrast, patients with a survival advantage with CABG, such
as those with three-vessel disease, have an annual mortality rate
greater than or equal to 3%. Coronary angiography is appropriate
for patients whose mortality risk is in this range.
Noninvasive
test findings that identify high-risk patients are listed in Table
23. Patients identified as high risk are generally referred for
coronary arteriography regardless of their symptomatic status. When
appropriately used, noninvasive tests are less costly than coronary
angiography and have an acceptable predictive value for adverse
events (12,13,14,37,485,894).
This is most true when the pretest probability of severe CAD is
low. When the pretest probability of severe CAD is high, direct
referral for coronary angiography without noninvasive testing has
been shown to be most cost-effective (see Section III.A), because
the total number of tests is reduced (335).
1.
Coronary Angiography for Risk Stratification in Patients With Chronic
Stable Angina
Recommendations
Class
I
1.
Patients with disabling (Canadian Cardiovascular Society [CCS] classes
III and IV) chronic stable angina despite medical therapy. (Level
of Evidence: B)
2.
Patients with high-risk criteria on noninvasive testing (Table
23) regardless of anginal severity. (Level of Evidence:
B)
3.
Patients with angina who have survived sudden cardiac death or serious
ventricular arrhythmia. (Level of Evidence: B)
4.
Patients with angina and symptoms and signs of CHF. (Level of
Evidence: C)
5.
Patients with clinical characteristics that indicate a high likelihood
of severe CAD. (Level of Evidence: C)
Class
IIa
1.
Patients with significant LV dysfunction (ejection fraction less
than 45%), CCS class I or II angina, and demonstrable ischemia but
less than high-risk criteria on noninvasive testing. (Level
of Evidence: C)
2.
Patients with inadequate prognostic information after noninvasive
testing. (Level of Evidence: C)
Class
IIb
1.
Patients with CCS class I or II angina, preserved LV function (ejection
fraction greater than 45%), and less than high-risk criteria on
noninvasive testing. (Level of Evidence: C)
2.
Patients with CCS class III or IV angina, which with medical therapy
improves to class I or II. (Level of Evidence: C)
3.
Patients with CCS class I or II angina but intolerance (unacceptable
side effects) to adequate medical therapy. (Level of Evidence:
C)
Class
III
1.
Patients with CCS class I or II angina who respond to medical therapy
and who have no evidence of ischemia on noninvasive testing. (Level
of Evidence: C)
2.
Patients who prefer to avoid revascularization. (Level of Evidence:
C)
2.
Risk Stratification With Coronary Angiography
Coronary
angiography, the traditional gold standard for clinical assessment
of coronary atherosclerosis, has limitations. Coronary angiography
is not a reliable indicator of the functional significance of a
coronary stenosis and is insensitive in detection of a thrombus
(an indicator of disease activity) (203,490).
More
important, coronary angiography is ineffective in determining which
plaques have characteristics likely to lead to acute coronary events,
that is, the vulnerable plaque with a large lipid core, thin fibrous
cap, and increased macrophages (491-494).
Serial angiographic studies performed before and after acute events
and early after MI suggest that plaques resulting in unstable angina
and MI commonly produced less than 50% stenosis before the acute
event and were therefore angiographically “silent” (495,496).
Despite
these limitations of coronary angiography, the extent and severity
of coronary disease and LV dysfunction identified on angiography
are the most powerful clinical predictors of long-term outcome (41,134,485,497,498).
Several prognostic indexes have been used to relate disease severity
to the risk of subsequent cardiac events; the simplest and most
widely used is the classification of disease into onevessel, two-vessel,
three-vessel, or left main CAD (96,499-501).
In the CASS registry of medically treated patients, the 12-year
survival rate of patients with normal coronary arteries was 91%
compared with 74% for those with one-vessel disease, 59% for those
with two-vessel disease, and 40% for those with three-vessel disease
(p less than 0.001) (488). The
effect of LV dysfunction on survival was quite dramatic. In the
CASS registry, the 12-year survival rate of patients with ejection
fractions in the range of 50% to 100%, 35% to 49%, and less than
35% were 73%, 54%, and 21%, respectively (p less than 0.0001) (488).
The importance of proximal coronary stenoses over distal lesions
was recognized, and a “jeopardy score” was developed
in which the prognostic significance of lesions was weighed as a
function of lesion location (502).
Recent angiographic studies indicate that a direct correlation also
exists between the angiographic severity of coronary disease and
the amount of angiographically insignificant plaque buildup elsewhere
in the coronary tree. These studies suggest that the higher mortality
rate of patients with multivessel disease may occur because they
have more mildly stenotic or nonstenotic plaques that are potential
sites for acute coronary events than those with onevessel disease
(503). Whether new technology such
as magnetic resonance imaging and EBCT scanning will provide incremental
prognostic value by identifying and quantifying plaque and its components
remains to be determined (504).
For
many years, it has been known that patients with severe stenosis
of the left main coronary artery have a poor prognosis when treated
medically. In a hierarchical prognostic index, patients with severe
left main coronary artery stenosis were given a prognostic weight
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