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Stress Testing in Cardiac Evaluation*
Current Concepts With Emphasis on the ECG
Morton E. Tavel, MD, FCCP
(CHEST 2001; 119:907–925)
Key words: stress testing; treadmill testing
Abbreviations: CAD ⫽ coronary artery disease; MET ⫽ metabolic
equivalent
test combined with ECG was originally
T heusedstress
primarily for the detection of ST changes
secondary to myocardial ischemia. Modern exercise
testing, however, is not limited to observation of
these changes. Important information is derived
from exercise capacity, BP response, development of
arrhythmias, and whether or not symptoms such as
chest pain develop during exercise. This allows for
assessment of presence and severity of ischemia,
prognosis, overall functional capacity, and efficacy of
therapeutic interventions. Although stress testing is
often combined with radionuclide or echocardiographic imaging, I shall focus primarily on the ECG
component. The proper selection of stress tests in
clinical evaluation will also be discussed.
The major indications for performing a stress test
are summarized in Table 1. Table 2 lists the generally accepted contraindications for such testing, as
adapted from the guidelines provided by the American College of Cardiology/American Heart Association Task Force in 1997.1
Safety of the Exercise Test
Stress testing is a relatively safe procedure. Before
1980, an overall mortality rate of 1 in 20,000 tests
was observed. In the contemporary era, however,
this frequency has been found to be even lower,
generally ⬍ 1 in 50,000.2 Nonfatal complications,
such as myocardial infarction, occur at the rate of
* From the Indiana Heart Institute, Care Group, Inc, and the
Department of Medicine, Indiana University School of Medicine,
Indianapolis, IN.
Manuscript received March 16, 2000; revision accepted July 5,
2000.
Correspondence to: Morton E. Tavel, MD, FCCP, 8333 Naab Rd,
Suite 200, Indianapolis, IN 46260; e-mail: [email protected]
⬍ 4 per 10,000 tests.2 In subjects with histories of
ventricular tachycardia or fibrillation, serious but
nonfatal arrhythmias occurred during 2.3% of the
tests.3 In the absence of such a history, the incidence
of such complications is approximately 0.05%.
Types of Stress Tests
The most commonly performed stress test is the
graded exercise test, using either the treadmill or
cycle ergometer. The patient is generally subjected
to increasing workloads at 2- or 3-min intervals. The
test is stopped for any of the reasons listed in Table
3. The ECG is monitored not only during exercise
but also afterward, for 5 to 11% of patients with
abnormal responses may not display such findings
until reaching the recovery period4,5 (see below).
The protocol used for treadmill testing varies
among different institutions. One of the most widely
used is that of Bruce and Hornsten,6 but the procedure may be customized to allow for 6 to 12 min of
exercise.7 A modified version of this protocol is
detailed in Table 4 and is especially useful because it
facilitates extrapolation from maximum treadmill
performance to levels of work and recreational activity. It also allows for estimation of severity of
cardiac decompensation (New York Heart Association classes). The estimated workload is reported in
metabolic equivalents (METs), a unit that facilitates
comparison of different exercise protocols as well as
allowing for comparison with work or recreational
effort requirements. This term actually represents
the energy cost of activity in multiples of resting
oxygen consumption (1 MET ⫽ 3.5 mL/kg/min). Inasmuch as oxygen consumption is determined primarily by cardiac output in the absence of pulmonary
or skeletal limitations, this information allows for
rough estimates of cardiac function. Although oxygen
uptake is not actually measured in most clinical
laboratories, one can estimate these approximate
values simply by consulting published information
derived from the various treadmill workloads. InCHEST / 119 / 3 / MARCH, 2001
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Table 1—Reasons for Stress Testing
1. Diagnosis of CAD in patients with chest pain that is atypical
for myocardial ischemia.
2. Assessment of functional capacity and prognosis of patients
with known CAD.
3. Assessment of prognosis and functional capacity of patients
with CAD soon after an uncomplicated myocardial infarction
(before hospital discharge or early after discharge).
4. Evaluation of patients with symptoms consistent with
recurrent, exercise-induced cardiac arrhythmia.
5. Assessment of functional capacity of selected patients with
congenital or valvular heart disease.
6. Evaluation of patients with rate-responsive pacemakers.
7. Evaluation of asymptomatic men ⬎ 40 years with special
occupations (airline pilots, bus drivers, etc).
8. Evaluation of asymptomatic individuals ⬎ 40 years with two or
more risk factors for CAD.
9. Evaluation of sedentary individuals (men ⱖ 45 years and
women ⱖ 55 years) with two or more risk factors who plan to
enter a vigorous exercise program.
10. Assessment of functional capacity and response to therapy in
patients with ischemic heart disease or heart failure.
11. Monitoring progress and safety in conjunction with
rehabilitation after a cardiac event or surgical procedure.
creasing age and deconditioning reduce normal maximum values.8 In some clinics, the test is stopped at
an arbitrary target point of 85% of the predicted
maximal heart rate for the subject’s age. This maximal rate is estimated by subtracting the subject’s age
from 220. This practice is no longer recommended in
favor of stressing individuals to the point of exhaustion or the development of warning signs or symptoms (Table 3).1 If the subject can continue, I usually
terminate the test on reaching 100% of the expected
maximum heart rate for age.
The ECG and BP are monitored throughout
exercise and for several minutes thereafter. In most
instances, the test may be conducted by a properly
trained nonphysician,2 especially with subjects at low
risk for cardiac events. In subjects at high risk, ie,
with chest pain suggestive of angina pectoris or with
known heart disease, a physician should be in atten-
Table 2—Contraindications to Stress Testing
1.
2.
3.
4.
5.
6.
7.
8.
Very recent acute myocardial infarction (generally ⬍ 3–4 days).
Angina pectoris, which is unstable or present at rest.
Severe symptomatic or unstable left ventricular dysfunction.
Potentially life-threatening cardiac dysrhythmias.
Acute pericarditis, myocarditis, or endocarditis.
Acute pulmonary embolus or infarction.
Severe aortic stenosis.
Noncardiac illness that precludes physical exertion, ie, acute
thrombophlebitis or deep vein thrombosis, serious general
illness, dissecting aneurysm, neuromuscular or arthritic
conditions, and inability or lack of desire or motivation to
perform the test.
Table 3—Indications for Terminating Exercise Testing
1. Drop in systolic BP of ⬎ 10 mm Hg from baseline BP despite
an increase in work load, especially when accompanied by
symptoms or signs of ischemia.
2. Moderate-to-severe angina.
3. Increasing nervous system symptoms (eg, ataxia, dizziness, or
near syncope).
4. Signs of poor perfusion (cyanosis or pallor).
5. Maximum fatigue or patient’s desire to stop.
6. Sustained ventricular tachycardia, increasing multifocal
ventricular ectopy, supraventricular tachycardia, heart block, or
bradyarrhythmias.
7. ST elevation (ⱖ 1.0 mm) in leads without diagnostic Q waves
(other than AVR).
8. Excessive ST depression (⬎ 2 mm horizontal or downsloping),
especially if accompanied by chest pain or other signs of
ischemia.
9. Excessive BP rise (⬎ 250 mm Hg systolic and ⬎ 115 mm Hg
diastolic).
dance or in close proximity during the test. In all
instances, a physician should be near enough to be
readily available should there be an emergent need.
BP Response to Exercise
In response to the increased stroke volume and
systolic contractile force, the systolic BP normally
rises progressively with increasing workloads, reaching approximately 160 to 220 mm Hg with maximum
effort. Because exercise lowers overall peripheral
vascular resistance, the diastolic pressure exhibits
little or no change (⬍ 10 mm Hg). If the systolic
pressure fails to rise to ⱖ 130 mm Hg or falls by
ⱖ 10 mm Hg in response to exercise, this frequently
indicates left ventricular dysfunction and often signals the presence of severe coronary artery disease
(CAD) associated with extensive myocardial ischemia.9,10 However, possibly in a substantial number
of patients, myocardial ischemia may produce an
abnormal fall in BP, presumably resulting from an
excessive vasodilator reflex in nonexercising vascular
beds.11 In this instance, cardiac output actually may
be increased during exercise.
An abnormal rise in exercise systolic pressure to a
level ⱖ 214 mm Hg in a subject with a normal
resting pressure predicts increased risk for future
sustained hypertension, estimated at approximately
10 to 26% for the next 5 to 10 years.12 This is
associated with a relatively high prevalence of left
ventricular hypertrophy.13 Some investigators12 have
found a slightly greater 5- to 10-year rate of subsequent cardiovascular events within this group, but
others14 have not observed this outcome.
Normally, the systolic pressure falls rapidly after
cessation of exercise, dropping by an average of
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Table 4 —Relationship Between Treadmill Workloads,
General Activities, and Cardiac Classification (New
York Heart Association)
METS
(Approx.)
Functional
Class
(NYHA)
1.7 mph
0% grade
1.8
IV
1.7 mph
5% grade
3
III
1.7 mph
10% grade
5
II
2.5 mph
12% grade
7
I
Treadmill
Level
3.4 mph
14% grade
9–10
0
4.2 mph
16% grade
11–12
0
Equivalent
Environmental Activities
Minimal: wash/shave, dress,
desk work, writing,
sewing, piano playing,
walk 1.5 mph
Very light: drive car,
clerical and assembly
work, shuffleboard,
billiards, walk 3 mph
Light: clean windows, rake,
wax floors, paint, stock
shelves, light welding
and carpentry, golf,
dancing (waltz), table
tennis, walk 3.5 mph
Moderate: light gardening,
lawn mowing (level),
slow stair climbing,
exterior carpentry,
doubles tennis,
badminton, walk 4 mph
Heavy: saw wood, heavy
shoveling, tend furnace,
moderate stair climbing,
canoeing, fencing,
singles tennis, jogging
5–6 mph
Very heavy: carry loads
upstairs, rapid stair
climbing, heavy labor,
lumberjack, racquetball,
basketball, ski touring,
run 6 mph
ⱖ 15% at 3 min after stopping. Myocardial ischemia
may reduce the rate at which this level falls: a 3-min
postexercise level of ⱖ 90% in comparison with the
peak systolic level during exercise suggests the presence of ischemia.15–17 To minimize the inaccuracies
of BP measurement at peak exercise, McHam et al17
suggested comparing pressures at 1 and 3 min after
exercise. Abnormality existed if the value at 3 min
equaled or exceeded that at 1 min. Such a retarded
pressure drop is an insensitive indicator of ischemia,
but it is fairly specific for this disorder, reportedly
exceeding 80%.17 Although the mechanism for this
abnormal pressure response is uncertain, it may
result from ischemic suppression of left ventricular
function during exercise combined with the subsequent recovery of contractility during recovery. This
response has been found usually to signal profound
and extensive ischemia, with the systolic pressure
ratio increasing proportionally with the number of
diseased coronary arteries.16
Heart Rate Response to Exercise
In general, the heart rate rises proportionately
with the intensity of the workload. Excessively rapid
rises in rate result primarily from reduced left ventricular stroke volume, which, in turn, may be caused
by physical deconditioning or cardiac disease. Under
such circumstances, the heart rate reaches its peak
level relatively early, and this limits maximum exercise capacity. However, when the heart rate response
to exercise is excessively attenuated (in the absence
of rate-limiting drugs), this condition is termed
chronotropic incompetence. Patients showing this
response often have significant organic heart disease,
and among patients with known or suspected coronary disease, it is independently predictive of higher
all-cause mortality.18 Unfortunately, however, definitions of chronotropic incompetence vary: they
range from the inability to achieve 85% of expected
maximum heart rate, to failure to achieve 100 beats/
min at maximal exertion,19 to heart rate responses in
terms of percentage or standard deviations around a
mean heart rate for each stage on the treadmill.18,20
Because of such limitations, analysis of cardiac chronotropic responses currently has limited practical
applicability.21
The rate with which the heart rate slows in the
early recovery period can also provide information
about ventricular function and prognosis. A recent
study by Cole et al22 demonstrated that a drop in rate
by ⱕ 12 beats/min at 1 min after peak exercise
during the cool-down phase in early recovery (while
walking 1.5 mph at 2.5% grade) signaled a poor
prognosis. These subjects were found to have a
subsequent 6-year mortality rate four times greater
than those have with a more rapid fall in heart rate.
The retarded heart rate drop during recovery probably signifies reduced vagal tone, which is often
associated with decreased myocardial function and
exercise capacity. An abnormal rate drop may add
independent prognostic information that extends
beyond such factors as effort tolerance and rate
response during the exercise period.
Cardiac Auscultatory Findings
Cardiac auscultation should be performed before
and immediately after exercise. Resting abnormalities, such as murmurs and third and fourth heart
sounds, should be noted and compared with postexercise findings. This facilitates recognition of important valvular abnormalities, such as aortic stenosis,
that might preclude or modify testing. I have also
encountered individuals with hypertrophic subaortic
stenosis in whom intense systolic murmurs became
manifest only after exercise. The appearance of a
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third heart sound or mid-diastolic gallop sound after
exercise is usually indicative of reduced resting
systolic function of the left ventricle, which may be
associated with cardiomyopathy or prior infarction,
often associated with diabetes mellitus and left bundle branch-block, although extensive stress-induced
ischemia is occasionally found.23
Recording Techniques
The conventional 12-lead ECG is the most widely
chosen one for the graded exercise test. Almost all
the significant ST-segment changes, however, can be
demonstrated in leads I and V3 through V6,24 and
approximately 90% of that information is contained
in lead V5. Some investigators have suggested that
the addition of right precordial leads, ie, leads V1R
through V4R, may improve the diagnostic accuracy in
detection of ischemia in general, especially in the
distribution of the right and circumflex left coronary
arteries.25,26
Equipment for computer averaging of the ECG
signals is commonly available, and this provides
assistance in the analysis of various changes— especially ST depression. I agree with others27 who have
noted that such records often produce spuriously
abnormal ST changes. Thus, the clinician should
always evaluate the actual ECG recording strips.
Criteria for a Positive Exercise Test:
Conventional Criteria
Horizontal or Downsloping ST-Segment Depression
of ⱖ1 mm
The PR segment is the reference point with which
the ST segment is compared (Fig 1). The criterion of
ⱖ 1 mm of horizontal or downsloping depression
(Fig 1, D and E) is the most generally accepted.
Junctional (J point) depression with slowly upsloping
ST segments (Fig 1C) also is generally considered to
be an abnormal response,28 –30 although the definition of slowly upsloping varies. Various investigators31 have reported that including upsloping ST
responses that remain 1 to 2 mm below the baseline
at 60 to 80 ms after the J point significantly increases
test sensitivity without degrading specificity. However, Sansoy et al32 noted that specificity was reduced, especially if 1-mm depression was selected at
80 ms. For this reason and until further data are
available, in the case of upsloping ST segments, I
agree with others33 who suggest using 1.5-mm depression at 80 ms after the J point as a reasonable
criterion for a positive response.
The depth of ST depression caused by ischemia
appears to be influenced by the overall amplitude of
the ECG signal as displayed by the R-wave height in
lead V5. Hollenberg et al34 reported that increased
R-wave amplitude might give rise to exaggerated ST
depression during exercise. Accuracy was improved
by normalizing the ST depression for the R-wave
amplitude. Ellestad et al35 noted that the correction
of ST depression for R-wave amplitude is especially
useful in subjects with a low R wave in V5. This
group36 found that if the R wave decreases by ⱖ 1
mm in V5 at the end of exercise, ST depression of
ⱖ 0.5 mm constituted a positive ischemic response
and would thereby increase the sensitivity of the test
to detect disease. Although of interest, these observations require further confirmation, for Froelicher
et al37 were unable to find improvement in test
accuracy by adjusting for R-wave amplitude.
ST-Segment Elevation
Although horizontal or downsloping ST-segment
depression is the typical ischemic response in stress
testing (in all leads except aVR), some patients
exhibit ST-segment elevation of ⱖ 1 mm (Fig 1F).
Generally, in the absence of prior infarction, this
finding is uncommon but implies severe transmural
ischemia exceeding that associated with isolated ST
depression.38 The reported incidence among patients with chest pain ranges from 0.2 to 1.7%.38 – 42
High-grade proximal coronary stenosis is usually
found, and this combination is associated with an
ominous prognosis.38 The correlation between the
site of the ST-segment elevation and the artery
involved is generally quite good.38 – 43 Probably representing a variant of ST elevation, isolated transient
increase in height of T waves in the anterior leads (V1
through V3) strongly suggests severe narrowing of
the left anterior descending coronary artery.44
Exercise-induced ST-segment elevation is seen
most commonly in patients who have had previous
myocardial infarctions.40,41 Most studies demonstrated an incidence of 14 to 27%.40 – 42,45–50 Patients
with anterior myocardial infarction are more likely to
have exercise-induced ST-segment elevation than
are those with inferior myocardial infarction.49,51 The
ST-segment elevation almost always occurs in the
leads with abnormal Q waves.50 It also is associated
with a left ventricular wall motion abnormality,
either dyskinetic or akinetic, in the corresponding
site in ⬎ 90% of cases.41,50 –52 Overall poor left
ventricular systolic function is usually found.45,52
Although some studies suggest that such ST changes
denote residual myocardial ischemia and contractile
reserve within this infarct area,53,54 passive segmental left ventricular wall motion abnormality (with or
without aneurysm formation) is probably the under-
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Figure 1. Schematic representation of various ST-segment patterns potentially produced by exercise.
A: normal; B: junctional depression that returns to baseline (level of PR segment) within 0.08 s (arrow);
C: junctional depression that remains below baseline at 0.08 s; D: horizontal ST depression; E:
downsloping ST depression;. F: ST elevation. See text for explanation.
lying mechanism for the ST-segment elevation in
most cases.54 Findings in one study,55 however,
suggested that residual viability could be found only
in those instances in which ST elevation was associated with reciprocal ST depression in those leads
taken from the opposite side of the heart. In this
context, therefore, ST depression may simply be a
secondary response to remote ischemia rather than a
primary marker of ischemia in itself—as is the usual
interpretation. In the case of prior inferior myocardial infarction, the ST elevation found accompanying
the Q waves in the inferior leads (II, III, and aVF)
often gives rise to reciprocal ST depression in the
high lateral leads (I and aVL).56
Ten to 30% of patients with variant angina also
may have ST-segment elevation with exercise.51 The
leads that show ST-segment elevation are usually the
same leads that record elevation during angina at rest.
All studies51,57,58 regularly report the occurrence of
spasm of a major coronary artery supplying the area of
the myocardium corresponding to the site of the STsegment elevation. Most patients with variant angina
and exercise-induced ST-segment elevation, however,
also have significant fixed coronary lesions.59
Transient, exercise-induced ST elevation has been
reported to occur in conjunction with acute pericarditis60 and may be mistaken for ischemic pain in the
acute care setting. As noted previously, patients with
known pericarditis are usually not subjected to stress
testing. When the diagnosis is uncertain, however,
persistence of ST elevation in response to exercise
stress testing may aid in the distinction between
pericarditis and early repolarization (a normal variant) inasmuch as in the latter condition, ST elevation
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returns to the isoelectric line.61 Exercise-induced
resolution of ST elevation, however, although uncommon, may occur in pericarditis as well.62
Less Commonly Used or Controversial
Criteria
The degree of ST-segment displacement in relation to the increase in heart rate (⌬ST/HR index)
with exercise has been suggested by some investigators to be a more accurate indicator of the presence
and severity of CAD.63– 67 This method requires
meticulous or computerized measurement of ST
displacement. Other studies68 –71 have not demonstrated the superiority of the ⌬ST/HR index in the
prediction of CAD. The usefulness of changes of
the heart rate-adjusted ST-segment depression in
the detection of CAD, therefore, remains controversial72 and, at best, may add only limited incremental
diagnostic value.73 Thus, this method has not gained
wide acceptance.
Transient inversion of U waves— even in the
absence of an abnormal ST-segment response— has
been suggested as a marker of extensive ischemia in
the anterior myocardium74 or elsewhere.75 Analogous to U-wave inversion, others76,77 have found that
exercise-induced increased magnitude of the U wave
in the precordial leads (ⱖ 0.05 MV) was strongly
suggestive of ischemia in the distribution of the left
circumflex or right coronary arteries, presumably
representing reciprocal changes from posterior Uwave inversion when myocardial ischemia occurred
in this latter location. Detection of all U-wave
changes is difficult in the presence of tachycardia, a
factor that limits the usefulness of these observations.
Bonoris et al78 initially reported an increase in the
R-wave amplitude immediately after exercise in patients with severe multivessel coronary artery narrowing and ventricular dysfunction, presumably
caused by transient ventricular dilatation. The results
of later studies varied, some supporting and others
not supporting the original observation.79 – 84 Nevertheless, although the sensitivity of this finding is low,
when the R-wave amplitude increases by ⬎ 2 mm at
peak exercise, this has been said to strongly suggest
ischemia.85 In general, however, analysis of R-wave
amplitude is not used in clinical practice.
Normally, the Q-wave depth in lead V5 increases
in response to exercise,86,87 presumably because of
septal thickening in response to inotropic stimulation. A decrease or no change in this wave has been
found with stenosis of the left anterior descending
coronary artery, usually in association with multivessel disease.86
The P wave shortens normally by approximately
0.02 s in response to exercise, whereas in the presence of ischemia, it may lengthen slightly or remain
unchanged.88 Transient elevation of atrial and left
ventricular filling pressure induced by ischemia is
the assumed mechanism for such P-wave prolongation. This interesting observation, if confirmed, may
provide a useful secondary means to confirm the
significance of other changes, such as ST depression.
The mean frontal plane QRS axis normally shifts
toward the right in response to exercise. Exerciseinduced leftward axis shift89,90 or absence of rightward shift89 is reported to be highly specific for
narrowing of the left anterior descending coronary
artery, presumably caused by ischemia of the left
anterior fascicle. However, transient rightward axis
shift to ⬎ 90° is a rare occurrence, but said to be
highly specific for CAD,91 presumably as a consequence of septal ischemia.
Exercise induction of complete right or left bundle
branch block is generally nonspecific. When found
together with other evidence of ischemia, however,
such as angina pectoris, the conduction abnormality
is said to be strongly suggestive of myocardial ischemia, especially in the distribution of the proximal
left anterior descending coronary artery.90
The QRS duration normally remains unchanged or
shortens slightly in response to exercise. In the
presence of ischemia, the QRS may lengthen slightly
(⬎ 3 to 5 ms) and this may allow detection of
ischemia with greater sensitivity and specificity than
ST segment changes alone,92–95 even in patients with
recent myocardial infarction.96 Michaelides et al95
found that the QRS prolongation correlated with
severity of ischemia, prolonging progressively with
one (9.7 ms), two (13.6 ms), and three (16.3 ms)
ischemic areas as demonstrated by nuclear scintigraphy. When prolongation of S waves (10 to 12 ms)
occurs in subjects with resting right bundle branch
block or left anterior hemiblock, this is believed to be
highly suggestive of left anterior descending coronary artery stenosis.97 Because of the small increments in duration of any of the above intervals,
higher recording paper speeds or computer-aided
measuring techniques such as signal averaging93,95
would be generally required to achieve sufficient
accuracy.
Normally, the QT interval (corrected for heart
rate) shortens with exercise. Some investigators have
found that this interval fails to shorten or lengthens
when ischemia is present.98,99 Others100,101 have
suggested that abnormal exercise-induced QT dispersion, ie, the difference between shortest and
longest QT intervals when multiple leads are compared, is greater in patients with ischemia. Measure-
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ment of this interval, however, is difficult, especially
when tachycardia is present, and this limits its
potential clinical value.
Methods to Validate the Presence of
Myocardial Ischemia
Despite its limitations, the coronary arteriogram
remains the most common standard against which
the diagnostic value (especially sensitivity) of stress
testing for CAD is measured. As noted, the use of
arteriography as a standard usually suffers from the
disadvantages of referral bias, ie, a positive ECG
stress test is often involved in the decision to select
those referred for subsequent coronary arteriography. The effect of such selective referral is to raise
falsely sensitivity estimates, and, conversely, to reduce falsely specificity values.
Noninvasive techniques (eg, stress thallium perfusion imaging or stress echocardiography) have also
been used to confirm the presence of coronary
disease. When such studies are used to evaluate the
performance of stress ECG, referral bias can be
minimized, and this usually results in lower sensitivity but relatively high specificity values.
Accuracy of ST-Segment Depression in
Detection of Ischemia
Stress-induced ST-segment depression is probably
caused largely by reduction of perfusion to the
subendocardium, the zone most vulnerable to ischemia. The sensitivity of such changes in the detection
of coronary disease varies widely in published reports,102–104 undoubtedly reflecting various confounding factors such as referral bias, severity of
disease in the selected population, and so forth.
Overall, test sensitivity is most often found to lie in
the 60 to 70% range. In studies in which referral bias
was minimized, however, lower sensitivity values are
reported, falling in the range of 45 to 60%.37,105 In
general, the greater the degree and extent of ischemia, the more likely will ST depression occur, and,
therefore, the higher the sensitivity of the stress
ECG. Most investigators have reported a sensitivity
in the range of 40%, 66%, and 76% for one-, two-,
and three-vessel coronary disease, respectively.106,107
We have also found that with larger nuclear perfusion defects in response to stress imaging, ST depression was more often encountered.105 Notwithstanding the results of smaller studies,108 we have
also found that larger areas of hypoperfusion also
increased the average depth of ST depression.105
In general, the distribution of leads manifesting
ST-segment depression does not appear to be helpful in localizing the obstructive coronary lesions,105,106,109 –112 for as noted, the lead V5 is most
apt to reflect this change whenever ischemia is
present. However, some studies43,113 have noted that
ST depression of lead V1— either isolated or associated with other lead changes—suggests the presence
of ischemia in posterior myocardial regions, ie, in
those areas supplied by the left circumflex or right
coronary arteries. Such depression in these leads
presumably arises as a reciprocal response to ST
elevation posteriorly, a location usually inaccessible
to conventional lead systems. Extending these observations further, one group26 has suggested that ST
deviation in the right precordial leads (V3R and V4R)
may not only enhance the recognition of posterior
ischemia, but when these changes are combined with
abnormalities in the conventional lead systems, the
sensitivity of ECG stress testing in general could be
greatly enhanced for detection of coronary disease.
They claimed a sensitivity ranging from 89% in
single-vessel involvement to as high as 95% in triplevessel coronary disease. To enter the clinical mainstream, however, these latter observations require
confirmation.
In contrast to the almost universal changes produced in the left precordial leads (V4 through V6),
myocardial ischemia seldom produces ST depression
confined to the inferior leads (II, III, and aVF), and
when one encounters such a limited distribution, this
usually denotes a false-positive test response,105,114
possibly often attributable to P-wave repolarization
(see below).
In general, the myocardial location of ischemia
also appears to play no role in the likelihood of ST
depression,105,110 for we have demonstrated that the
likelihood of its appearance depends primarily on the
extent of ischemia rather than its location.105
The configuration, time of onset, and duration of
depressed ST segment during and after treadmill
exercise have important diagnostic significance.115
Multivessel or left main coronary disease is present
in approximately 90% of patients who have changes
appearing at low workloads (Bruce stage I or II) or
persisting for ⬎ 8 min after exercise.116,117 Although
such early and prolonged ST responses are highly
specific for ischemia, some studies suggest that they
correlate less well with subsequent prognosis,118 and
even arteriographic or scintigraphic severity may be
variable.119 Although T-wave changes alone are not
helpful in diagnosis, the presence of deep T-wave
inversion (ⱖ 5 mm) when combined with ST depression has been found to be highly specific for multivessel CAD with multiple severe narrowings.120
ST-segment depression occasionally begins only
after cessation of exercise. The diagnostic and
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prognostic significance of such a delayed response
is generally similar to those occurring during exercise121–123; however, when the onset of such a change
is delayed by ⬎ 2 to 3 min into recovery, this
suggests a false-positive response.124 When ST
changes during exercise are equivocal, the finding of
progressively greater downsloping ST depression
during recovery is a fairly specific sign of severe
ischemia and also signals a greater incidence of
cardiac events in follow-up.125
The pattern of regression of ST changes in the
recovery period may be useful in distinguishing
ischemic responses from those encountered occasionally in normal subjects who are falsely positive.124,126 In true ischemia, the major ST depression
tends to coincide with the termination of exercise
and continues— often intensifying—for ⱖ 2 to 3 min
after cessation.124 The persistence of this depression
in recovery usually parallels its onset, ie, when it
begins early at low workloads, it is more persistent
during recovery. When it reaches a maximum later in
the exercise phase, it usually regresses relatively
early in recovery, but it usually continues for at least
3 min after stopping. In contrast, false-positive ST
depression tends to reach its maximum immediately
before and at peak exertion but regresses quickly on
cessation, frequently returning to normal within 1 to
3 min of recovery. In this latter instance, as the heart
rate slows in recovery, the depth of ST depression is
less when compared with corresponding cycle lengths
during the exercise phase, whereas those subjects with
true ischemia usually show equal or greater ST displacement at comparable cycle lengths.126
The development of typical anginal chest pain
during the test generally signifies fairly extensive ischemia and thus increases the likelihood of ST changes,
adding significantly to test sensitivity.105 Moreover,
typical chest pain during testing is almost as predictive
of ischemia as is ST-segment depression.127
As already noted for test sensitivity, the specificity
of ST depression in the evaluation of coronary
ischemia has also been found to vary considerably,
with a mean value derived from a meta-analysis
reported to be 72%.102 Referral bias, however, probably reduced these values spuriously, for when this
type of bias is minimized, these values generally
approach or exceed 90%.37,128,129
Differences in results of stress tests between men
and women have been the subject of considerable
controversy. In general, women are far more likely
than men to manifest a false-positive response,130 –132
but the difference may be attributable to the lower
rate of CAD in the populations of women subjected
to testing. Based on Bayes theorem, the lower
general prevalence of CAD among women results in
a relatively low predictive value of a positive test in
this group. Some investigators133 have suggested that
hormonal effects, especially those of progestin,
might be responsible for the production of falsepositive ST responses. This effect, if present at all,
would be small, for the rate of false-positive stress
tests in premenopausal women is low129and only
marginally greater than that of men.
Test specificity, ie, the percentage of negative
responders in a population known to be free of
disease, is of utmost importance in clinical evaluation, and many mistakenly believe that this value is
unacceptably low in women. For proper determination of test specificity, a group must be defined that
is uniformly proven to be free of disease and in
which no prior ECG tests have been performed.
Coronary cineangiography is often used as the definitive test to rule out CAD. Unfortunately, such a
design is basically flawed because it is a rare individual who has not been subjected to prior stress testing
and in whom the results of this testing were not
instrumental in the decision to obtain the cineangiographic study. This process produces so-called referral bias, ie, the inclusion of an inordinately high
percentage of positive test responders in a diseasefree group selected in this manner, thus yielding
falsely low specificity values. Such bias may produce
greater distortions of test specificity in women simply because, as noted above, falsely abnormal stress
responders are more plentiful in mixed populations
of women (with and without disease) from which
these subjects are drawn. When this type of bias is
minimized, however, the difference in specificity
between the sexes all but disappears, with a falsepositive response rate of ⱕ 10% for each.128,129
Therefore, in accordance with Bayesian principles, a
negative test result encountered in a subject from an
unselected population of women generally carries a
high negative predictive value and thus is useful in
excluding CAD. These data suggest that, in general,
the initial evaluation of an individual woman should
be identical to that of a man, ie, accomplished with a
standard ECG stress test. It need not involve costly
nuclear or echocardiographic techniques unless the
former test result is positive—a relatively uncommon
occurrence in the absence of coronary disease.
Causes of Positive Results of Exercise
Tests in the Absence of CAD
Numerous situations appear to give rise to exercise-induced ST depression in the absence of obstruction to the major coronary arteries. Mechanical
lesions that place a greater burden on left ventricular
dynamics and oxygen requirements include such
abnormalities as mitral or aortic valvular dysfunc-
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tion,134,135 pulmonary hypertension,135 pericardial
constriction,136 and left ventricular hypertrophy.136,137 Relative coronary insufficiency is probably
also the responsible mechanism in patients with left
ventricular hypertrophy. The frequency of positive
test results in such cases has been found to be as high
as 38%.138 Patients with increased left ventricular
mass, even in the absence of standard ECG voltage
criteria for this diagnosis, may have false-positive
ECG exercise responses.137,138
A wide variety of miscellaneous situations has also
been associated with falsely positive ST responses to
exercise.139 These include digitalis administration,140,141 hypokalemia,142,143 normal postprandial
changes,144 hyperventilation,145,146 postural changes,147 vasoregulatory abnormalities,148,149 mitral valve
prolapse,150,151 pectus excavatum,152 and intraventricular conduction defect including left bundle
branch block and Wolff-Parkinson-White syndrome.153–155 There is undoubtedly no common
mechanism for ST shifts in these diverse situations;
however, effects brought about by electrolyte shifts
and sympathetic nervous stimulation at the cellular
level may play an important role.
Digitalis is known to cause a false-positive exercise
test result in both normal subjects and in patients
with heart disease,140,141,156 occurring as often as
25% in healthy subjects,141 showing a greater prevalence with increasing age. Hamasaki et al156 found
that digitalis-induced ST-segment depression occurs
gradually as the heart rate increases in response to
exercise, a pattern differing from that usually seen in
myocardial ischemia, in which the ST depression
progresses more rapidly as peak heart rates are
approached. This might aid in distinguishing between drug effect and ischemia.
Hypokalemia is often associated with abnormal
exercise responses,142 and these changes can be
abolished after potassium repletion. Therefore, in
patients who are taking diuretics, the results of the
ECG stress test should be interpreted with caution.
Food intake may induce ST-segment and T-wave
changes in the resting ECG.157 Significant ST depression also may develop after glucose ingestion in
subjects who otherwise had normal exercise
ECGs.144 For this reason, exercise testing should be
proscribed until ⱖ 2 h after a meal to avoid this
source of variability.
Although usually causing changes primarily confined to the T waves, hyperventilation is known to
produce ST-segment changes in response to exercise
that mimic those of myocardial ischemia.145,146,158 If
this cause is suspected in a given individual with
suspicious stress-induced ST changes, that subject
may be instructed to voluntarily hyperventilate for a
period of 2 to 3 min during rest and with ECG
monitoring. If ST changes are produced by this
maneuver, they are compared with those encountered during the stress test, and if similar, this
suggests a false-positive result induced by hyperventilation. This maneuver, however, should be selectively performed only after the standard stress test,
for routine performance before the test is usually
unnecessary and may produce dizziness and discomfort and interfere with the proper execution of the
standard test.
A peculiar syndrome, sometimes labeled syndrome X, is occasionally encountered, especially in
young and middle-aged women, consisting of anginal-type chest pain and abnormal exercise ECG but
normal coronary arteriograms.159 Exercise-induced
coronary spasm and microvascular disease160 are
possible causes of this syndrome. Therefore, in this
context, the abnormal ECG stress test result may not
be truly false positive.
Patients with the mitral valve prolapse and normal
coronary arteriograms may have false-positive exercise responses.150 This phenomenon is clinically important because chest pain and vasoregulatory abnormalities are occasionally encountered in these
patients.
The secondary ST-segment and T-wave changes in
patients with intraventricular conduction defects
such as left bundle branch block, ventricular paced
rhythm, and Wolff-Parkinson-White (preexcitation)
syndrome interfere with proper interpretation of the
exercise response.153–155,161,162 Both false-positive
and false-negative responses may be seen in patients
with left bundle branch block. Studies in a limited
number of patients, however, suggested that the exercise test might be useful even if this latter conduction
abnormality is present.163,164 Recently, Ibrahim et al165
found that additional exercise-induced J point depression in leads II, aVF, and V5 was suggestive of
ischemia in this group. Most useful in their study was
a change of ⱖ 0.5 mm in lead II. This finding, if
confirmed, would be of significant clinical value.
False-positive changes are particularly common in
patients with the Wolff-Parkinson-White syndrome,154 being observed in as many as 100% of such
cases.155
In the case of right bundle branch block, the
resting anterior ST-T changes secondary to this
conduction abnormality interfere with interpretation
of the exercise response. Thus, changes in leads V1
through V3 often falsely suggest ischemia.166 The test
is still reliable if the ST segment depression is
recorded in leads V4 through V6. In one small
study,167 however, this conduction abnormality was
found to be capable of masking the usual ischemic
ST depression in these latter leads, thus producing
false-negative ST responses to stress.
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Exaggerated atrial repolarization waves may produce spurious depression of ST segments.168 –170 The
atrial repolarization wave is directionally opposite to
the P wave and can extend well into the ST segment.
Thus, with exercise-induced tachycardia, P wave and
atrial repolarization wave amplitudes increase, and
the PR segment shortens, thus shifting the atrial
repolarization wave toward the ST segment. In practice, this phenomenon may be suspected when apparent ST depression is found together with a prominent P wave with a short, sharply downsloping PR
segment, especially notable in the inferior leads.
Causes of False-Negative Response
Apart from the inherent limitations of sensitivity of
the exercise test in the detection of myocardial
ischemia, certain drugs are known to limit its value
even further. Drugs which limit the heart rate
response to exercise (␤-adrenergic blocking agents,
diltiazem, and verapamil) reduce the heart rate and
maximum systolic arterial BP during exercise, thus
decreasing the left ventricular work and myocardial
oxygen requirements and reducing or eliminating
the ST-segment depression.171 In the process of
increasing exercise capacity, nitrates may also prevent or minimize changes in exercise ECG.172 In
general, if one wishes to maximize test sensitivity,
treatment with any of the drugs noted above should
be withdrawn for a sufficient period to allow removal
from the body before testing. Depending on the
information desired from the test and the need for
continued medication, however, the clinician may
decide to perform the test in selected cases without
drug withdrawal.
Exercise Testing in Patients With
Abnormal Resting ECGs
A number of reports suggest that exercise testing
may be of value even when the resting ECG is
abnormal.173–175 Most of the patients with abnormal
resting ECGs show nonspecific ST-segment and
T-wave changes. In general, additional ST depression of ⱖ 1 mm with exercise has a diagnostic
accuracy approaching that found in the absence of
resting changes.173–175 Such changes also have been
found to have similar prognostic significance as those
found in patients with a normal resting ECG.175
In the presence of resting T-wave inversion, normalization of this abnormality in response to exercise
may occur in different clinical settings176 –178: it may
result from regional myocardial ischemia or abnormal left ventricular wall motion, but may also occur
in normal subjects. Thus, in general, this finding has
little specificity. However, if such normalization occurs in conjunction with an infarcted dysfunctional
myocardial zone, it may indicate higher coronary
flow reserve, and this in turn suggests better preservation of coronary microcirculatory function and the
likely presence of myocardial viability.176,177 This
concept, however, has been challenged by others.52
ST-segment elevation may be seen in the resting
ECGs of healthy subjects because of early repolarization. In such cases, the ST segment returns to the
isoelectric baseline with exercise, whereas those with
significant CAD may have horizontal ST-segment
depression.179 Therefore, even in the presence of ST
elevation in the baseline ECG, the usual criteria for
the interpretation of the exercise test are probably still
applicable. As noted above, persistent or increasing ST
elevation during exercise may be encountered in myocardial ischemia, prior infarction, or pericarditis.
Prognostic Value of Exercise Testing
When large groups of unselected individuals are
screened with stress tests, studies consistently show
that subjects manifesting abnormal ST responses are
at greater risk for subsequent cardiovascular events
(angina, acute myocardial infarction, or sudden
death).180 –186 In general, after a follow-up period of
5 to 13 years, those with positive ECG responses
show approximately a four- to sixfold greater incidence of such events in comparison with those
responding normally to stress. Inability to exercise
⬎ 6 min on a standard Bruce protocol (approximately
6 to 7 METs) and inability to increase the heart rate to
85% of age-predicted normal maximum values also
were significant indicators of increased risk of coronary events. Individuals demonstrating high exercise
tolerance (ⱖ 10 METs) generally enjoy an excellent
prognosis, regardless of the ECG response and even
in the presence of known CAD.187–189
The combination of various exercise test variables
has improved the estimation of long-term prognosis.187,190 Variables found to be independently associated with time to cardiovascular death were
weighted to create an equation that calculates a
numeric score. The Duke score,187 which is the most
widely used and confirmed by others,175 is based on
three exercise variables: exercise tolerance in METs,
the largest measured ST-segment depression during
exercise, and whether angina pectoris could be induced by the test. (Duke Score ⫽ exercise
time ⫺ 5 ⫻ {exercise-induced ST depression in
millimeters} ⫺ 4 ⫻ treadmill angina index. Where
exercise time is in minutes of Bruce protocol; ST
depression is largest stress-induced downward dis-
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placement in mm, and angina index is given as the
following: 0 for no angina during exercise, 1 for typical
angina, and 2 for angina leading to discontinuation of
exercise. The Duke score [DS] is then used to calculate
annual cardiovascular mortality [CVM]: CVM ⫽
⫺0.00018[DS]3 ⫺ 0.0071[DS]2 ⫺ 0.143[DS] ⫹ 1.60.)
A Long Beach Veteran’s Administration score190 incorporates slightly different variables but yields similar
prognostic information. The use of such indexes
enhances the practical value of stress testing far
beyond that obtained from simple analysis of ECG
changes alone, further emphasizing the importance
of using symptom-limited protocols for testing. Although patient management should be individualized, the projection of an annual mortality rate of
ⱕ 1% would usually warrant a conservative medical
approach to management in favor of aggressive
invasive or surgical procedures.
The induction of typical angina pectoris during
treadmill stress signifies that the extent of ischemia is
greater than in subjects lacking this symptom,105
although diabetics are generally less likely to experience pain. The subsequent survival rate decreases
incrementally in proportion to the reduction in
exercise duration and effort tolerance.191 As a rule,
those who have good exercise capacity (approximately ⱖ10 METs) enjoy a good prognosis, experiencing
a 5-year survival of ⱖ 95%. However, the probability
of survival is much lower in those patients who have
ⱖ 1 mm ST-segment depression and who are able to
achieve a level of exercise equivalent to only Bruce
stage 1 (5 METs) or lower. Survival at 5 years in this
latter group ranges from 50 to 72%. In view of the
data cited above, one may formulate the following
general strategy for the use of ECG stress testing in
deciding whether and which further tests are
required for patients with known or suspected
CAD. If an ECG stress test is negative or indicates
a low risk (yearly mortality ⱕ 1%), medical management with risk-factor control is generally preferred. For those demonstrating high risk (projected mortality ⱖ 5% yearly), direct intervention with
coronary cineangiocardiography should be
strongly considered. For those determined to be at
intermediate risk (1 to 5% annual mortality),
further stratification with nuclear imaging should
be considered before choosing further evaluation
or treatment.192 Multiple or extensive nuclear perfusion abnormalities signal the need for invasive study,
whereas a normal scan or one containing a small
defect warrants a conservative approach. Obviously,
initial evaluation with nuclear or echocardiographic
procedures with pharmacologic provocation is required for those individuals unable to exercise or
who possess disqualifying resting ECG abnormal-
ities. Moreover, other clinical features, such as age
and comorbidities, enter into these testing and
management decisions.
Exercise Testing After Myocardial
Infarction
To assess the presence of ischemia or left ventricular dysfunction and to gauge future risk more
effectively, stress testing is often used as early as 4 to
7 days after an acute myocardial infarction193,194 and,
more recently, 3 days after such an event.195 In the
past, it was performed typically after an interval of
ⱖ 2 months had elapsed.196 –199 The predictive value
of early testing, especially when symptom limited, is
similar to that of testing performed 6 weeks after
infarction.193,200,201 If performed early, exercise on
the treadmill is commonly stopped when the subject
reaches an arbitrary heart rate, which is generally
120 or 130 beats/min, or 70% of predicted maximum
heart rate for age. More recently, however, several
investigators193–195 have found that symptom-limited
testing could be performed early and safely in subjects with uncomplicated myocardial infarctions (average 4 to 7 days after the event). Stress-induced ST
depression after a single previous myocardial infarction usually identifies those with ischemia resulting
from multivessel coronary disease.45,48 A poor BP
response during exercise is suggestive of reduced left
ventricular function.199 With maximal testing, the
ability to achieve a high heart rate–systolic pressure
product (ⱖ 21,700) implies good myocardial blood
flow and a favorable prognosis (6 months mortality,
0.8% vs 2% in those failing to reach this product).202
Exercise-induced ST-segment elevation in leads possessing pathologic Q waves usually is associated with
greater impairment of left ventricular function because of more extensive damage rather than extent of
the CAD,203 but, as noted above, whether it indicates
the presence of viable myocardium is controversial.
Combining various features of stress testing enhances assessment of prognosis: exercise-induced
angina, ST-segment displacement, falling BP or failure to increase BP to ⱖ 110 mm Hg, repetitive
ventricular arrhythmias, poor exercise tolerance (⬍ 6
METs), and inability to reach exercise heart rate of
120 beats/min (in the absence of ␤-blockers) are
predictive of higher risk for future cardiac events
such as unstable angina, recurrent myocardial infarction, and cardiac death.193,194,196,204 –207 The estimated 1-year mortality ranges from approximately
1% if none of these features was present to 17% if
three or more were present. Similar findings have
been observed both in patients with Q-wave and in
those with non–Q-wave infarctions.193,194,208 Those
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receiving thrombolytic treatment apparently enjoy a
better prognosis even when these test results are
positive.207
With the increasing popularity of various stressimaging modalities, physicians must consider the
proper strategy of patient management after a myocardial infarction before discharge from the hospital.
In a meta-analysis,207 stress ECG was compared with
myocardial nuclear perfusion and ventricular function imaging. Positive results of all forms of testing
yielded relatively low positive predictive values for
subsequent events, ie, ⬍ 20% chance of death or
reinfarction in 1 year. In general, tests to detect
reduced left ventricular function (peak stress-induced ejection fraction ⱕ 40%) were more predictive of an adverse outcome, averaging from 30 to
40% chance of death or reinfarction in 1 year.
Those tests that disclosed myocardial perfusion
defects, such as ST depression or reversible nuclear perfusion or wall motion abnormalities, were
less predictive of subsequent events. However,
negative results of all tests were comparably and
independently predictive of lower (⬍ 10%) event
rates at 1 year.
From these data above, one might formulate the
following strategy for noninvasive testing after a
myocardial infarction. In patients undergoing immediate angiography or angioplasty, a predischarge stress test is generally superfluous, and this
test may be deferred until 4 to 6 weeks after
hospital discharge.195 In the remainder who have
sustained an uncomplicated infarction (absence of
congestive heart failure, reduced resting ejection
fraction, or other adverse markers such as persistent chest pain, hypotension, and so forth), one
would proceed first with an ECG stress test,
preferably symptom-limited in type. If such patients exercise to ⬎ 6 METs without ECG or
hemodynamic abnormalities, they are at low risk of
a recurrent cardiac event during the ensuing year.
Through this means, no further tests are required,
costs can be minimized, and the patient can be
reassured. If results of this test are abnormal or if
resting ECG abnormalities preclude assessment of
stress-induced changes, I suggest stress imaging
with nuclear or echocardiographic techniques. Exercise is the preferable form of stress unless
limitations of patient performance necessitate
pharmacologic stimulation with agents such as
dobutamine or dipyridamole. In those patients
with complicated infarctions or who exhibit evidence of reduced resting left ventricular function,
one would proceed directly to stress imaging or
invasive study.
Exercise ECG in Risk Assessment Before
Noncardiac Surgery
Stress testing may be useful in risk assessment
before any type of elective surgical procedure. The
indications for testing are basically the same as noted
in Table 1, especially categories 1 and 2. The features indicative of high risk for perioperative cardiac
events are, as expected, poor functional capacity,
marked exercise-induced ST-segment shift or angina
at low workloads, and a drop or an inability to
increase the BP with progressive exercise.209 Those
shown to be at low long-term risk generally may
proceed directly to surgery without further testing.
Patients requiring surgical procedures, however, especially for peripheral vascular disease, are often
unable to exercise, and, therefore, evaluation must
necessarily begin with nuclear or echocardiographic
imaging with pharmacologic provocation. Selection
for additional testing, including invasive procedures,
before elective surgery is generally the same as that
described above for the general population. This
subject has been reviewed previously by Chaitman
and Miller.209
Relationship Between Exercise Testing
and Ventricular Arrhythmias
Premature ventricular beats are often induced by
exercise. In studies of middle-aged or older subjects
without overt heart disease, approximately 3% or
more have premature ventricular beats at rest, increasing by more than twofold (to as high as 50%) at
peak exercise, which often includes the new appearance of repetitive ventricular ectopic beats.181,210 –212
The incidence of such arrhythmias appears to increase with age.213 In general, more arrhythmias are
seen on recovery than during exercise. Although
ventricular ectopy is more easily evoked in patients
with CAD than in normal subjects, the considerable
overlap between those with and without ischemia
prevents this finding from possessing diagnostic
value. The long-term prognosis of asymptomatic
subjects manifesting exercise-induced ventricular arrhythmias, including nonsustained ventricular tachycardia, appears to be benign.181,214
In patients with CAD, the reported incidence of
exercise-induced ventricular arrhythmias ranges
from 38 to 65%.211,212,215 In general, the survival rate
of patients with CAD, including those with recent
myocardial infarction, is decreased if they have
exercise-induced complex ventricular arrhythmias.205,216 –218 Some reports dispute such an association, however,219 at least in low-risk patients with
demonstrable stable coronary disease.220,221 Significant multivessel disease is likely to be present in
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patients with angina and exercise-induced ventricular arrhythmias,215,222 especially if ST-segment
changes consistent with myocardial ischemia also are
present.223
Thus, the appearance of ventricular arrhythmias in
response to exercise in asymptomatic subjects has no
diagnostic or prognostic value. When they are found
in association with known CAD or with other markers of ischemia, such as ST depression or anginaltype chest discomfort, they generally predict an
inordinately high incidence of subsequent cardiac
events.
Selection of a Stress Test in Initial
Evaluation
Authorities disagree about whether any form of
exercise testing should be performed in asymptomatic individuals.1 In this category, I believe it justifiable to test individuals with multiple risk factors for
atherosclerosis (including associated diseases such as
chronic renal failure), sedentary individuals who plan
to start vigorous exercise, and those who are involved
in occupations in which impairment might impact
public safety. The use of ultrafast (electron beam)
CT is being used with increasing frequency in
asymptomatic individuals for the detection of coronary artery calcification.224 The presence and
amount of calcium detected by this means appear to
correlate with the amount of atherosclerotic plaque,
but they do not necessarily signal the presence of
coronary arterial flow restricting disease. It may offer
an earlier means to assess risk and observe responses
to therapy. The proper role of this technique, however, is currently controversial and is under
review.225
In patients presenting to emergency facilities with
acute chest pain syndromes, stress testing with electrocardiography may provide an important means for
triage and management with the attendant reduction
of medical costs.226,227 In those subjects with suspected cardiac pain demonstrating a low or moderate
risk for immediate adverse outcomes, management
may proceed swiftly to include the following. First,
serum enzymes are assessed (total serum creatine
kinase and its MB isoenzyme and troponin levels),
and if these are normal, a treadmill test is performed
either immediately225 or after a 6-h observation
period with repeat enzyme determination.226 Individuals undergoing this strategy would include those
with ECGs that are normal or with only nonspecific
repolarization abnormalities, stable BP, no clinical
evidence of cardiac decompensation, and absence of
prolonged chest pain associated with dynamic ST
changes. A normal result of a stress test allows for
immediate hospital discharge, whereas an equivocal
or positive test result is followed by hospitalization
with additional study.
When given a choice among ECG and imaging
methods in evaluating patients with recurrent chest
pain with intermediate or high likelihood of a cardiac
origin, the physician should opt for the most direct
and cost-effective means of initial evaluation—the
ECG stress test. Men and women should be approached in the same fashion. Even though stress
nuclear and echocardiographic imaging are more
sensitive in the detection of ischemia, there is insufficient evidence to assume that information so obtained can be more cost-effective or used to improve
outcomes beyond that obtained through prognostic
assessment used in conjunction with stress ECG
alone. If the ECG changes suggest ischemia and
clinical circumstances warrant it, an imaging study
may then be used. When resting ECG abnormalities
preclude interpretation, then initial evaluation
should combine stress testing with imaging modalities. When patients are unable to exercise for any
reason or if an unsatisfactory rate response to exercise
is anticipated (as exemplified by the inability to withdraw treatment with rate-limiting drugs), then imaging
studies with pharmacologic provocation should be considered.
Concluding Remarks
Modern exercise testing with ECG monitoring
remains a cornerstone of cardiovascular evaluation,
providing a valuable source for several types of
information. (1) Changes in the ECG pattern—
especially depression of the ST segment—indicate
the presence and often the severity of myocardial
ischemia. (2) When combined with ECG changes,
symptoms of dyspnea and chest pain, limitation of
maximum performance, and BP response provide
valuable markers of the presence and severity of
disease and its prognosis. Combined with the history
and physical examination, a prognostic index indicative of low risk for future cardiovascular events may
allow the clinician to avoid aggressive and costly
procedures such as cardiac catheterization.228 (3)
Maximum effort tolerance is useful in gauging work
and recreational limitations and for use in monitoring efficacy of treatment and in prescribing a safe
exercise program. (4) Diagnostic and prognostic data
derived in this way can supplement those obtained
through simultaneously performed imaging techniques, ie, stress echocardiography or nuclear perfusion study.
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