Overview of Exercise Stress Testing

Abstract

Exercise stress testing is a non-invasive, safe and affordable screening test for coronary artery disease (CAD), provided there is careful patient selection for better predictive value. Patients at moderate risk for CAD are best served with this kind of screening, with the exception of females during their reproductive period, when a high incidence of false positive results has been reported. Patients with a high pretest probability for CAD should undergo stress testing combined with cardiac imaging or cardiac catheterization directly. Data from the test, other than ECG changes, should be taken into consideration when interpreting the exercise stress test since it has a strong prognostic value, i.e. workload, heart rate rise and recovery and blood pressure changes. Only a low-level exercise stress test can be performed early post myocardial infarction (first week), and a full exercise test should be delayed 4 to 6 weeks post uncomplicated myocardial infarction. The ECG interpretation with myocardial perfusion imaging follows the same criteria, but the sensitivity is much lower and the specificity is high enough to overrule the imaging part.

Full text

Ann Saudi Med 26(1) January-February 2006 www.kfshrc.edu.sa/annals
1
REVIEW
From the Department of
Cardiovascular Disease, King
Faisal Specialist Hospital and
Research Centre, Riyadh, Saudi
Arabia
Correspondence:
Suleiman M. Kharabsheh, MD
Consultant Cardiologist
Department of Cardiovascular
Diseases
King Faisal Specialist Hospital and
Research Centre
MBC 16
P.O. Box 3354
Riyadh 11211
Saudi Arabia
Tel: +966-1-442-7472
Fax: +966-1-442-7478
skharabsheh@kfshrc.edu.sa
Accepted for publication
February 2004
Ann Saudi Med 2006;26(1):1-6E
xercise stress testing has been used for decades as a noninvasive
test to diagnose and risk stratify coronary artery disease (CAD).
However, it lacks adequate sensitivity, which nevetheless de-
pends on the pretest probability of CAD in the population tested. e
overall sensitivity has ranged from 60% to 70% with a specificity of
85%.
1,2,3
Due to the innumerable criteria set for the EKG stress test
interpretation and reporting, a lot of confusion arises between institu-
tions. To make it easier on the practitioner at our institution, we have
adopted the criteria outlined in this review for interpretation of test
results.
Indications and safety of exercise testing
Although exercise testing is generally a safe procedure, both myocardial
infarction and death have been reported and can be expected to oc-
cur at a rate of up to 1 per 2500 tests. Good clinical judgment should
therefore be used in deciding which patients should undergo exercise
testing. Common indications and contraindications are listed in Table
1 e prognosis of the individual tested is not only linked to the result
of the test whether it is positive or negative, but also depends on the
exercise capacity, heart rate rise, heart rate recovery and blood pressure
rise and recovery.
Exercise capacity is based on metabolic equivalents (MET) achieved,
(one MET is defined as 3.5 mL O2 uptake/kg per min, which is the
resting oxygen uptake in a sitting position). Less than 5 METS is poor,
5-8 METS is fair, 9-11 METS is good, and 12 METS or more is ex-
cellent. An inability to exercise >6 minutes on the Bruce protocol, or
Overview of Exercise Stress Testing
Suleiman M Kharabsheh, Abdulaziz Al-Sugair, Jehad Al-Buraiki, Joman Farhan
Exercise stress testing is a non-invasive, safe and affordable screening
test for coronary artery disease (CAD), provided there is careful patient
selection for better predictive value. Patients at moderate risk for CAD
are best served with this kind of screening, with the exception of fe-
males during their reproductive period, when a high incidence of false
positive results has been reported. Patients with a high pretest prob-
ability for CAD should undergo stress testing combined with cardiac im-
aging or cardiac catheterization directly. Data from the test, other than
ECG changes, should be taken into consideration when interpreting the
exercise stress test since it has a strong prognostic value, i.e. workload,
heart rate rise and recovery and blood pressure changes. Only a low-
level exercise stress test can be performed early post myocardial infarc-
tion (first week), and a full exercise test should be delayed 4 to 6 weeks
post uncomplicated myocardial infarction. The ECG interpretation with
myocardial perfusion imaging follows the same criteria, but the sensi-
tivity is much lower and the specificity is high enough to overrule the
imaging part.

EXERCISE STRESS TESTING
Ann Saudi Med 26(1) January-February 2006 www.kfshrc.edu.sa/annals
2
an inability to increase heart rate (HR) to >85% of
maximum predicted heart rate (MPHR) are signifi-
cant indicators of increased risk of coronary events
with a 5-year survival ranging from 50% to 72%.
However, patients who attain >10 METS enjoy an
excellent prognosis regardless of the test result even
in the presence of known CAD, with a 5-year sur-
vival of 95%.
e heart rate should reach or exceed 85% of
MPHR calculated according to the formulae,
MPHR=220-age. e HR rises prortionately with
the intensity of the workload. An excessive rise in
rate results primarily from a reduced stroke vol-
ume, which in turn is often caused by physical de-
conditioning, cardiac disease or arrhythmias like
atrial fibrillation or supraventricular tachycardias
and other noncardiac abnormalities like anemia and
hypovolemia. In these situations the HR reaches its
peak early, which limits maximum exercise capac-
ity. An impaired chronotropic response to exercise
as defined by failure to achieve 85% of MPHR
and/or a low chronotropic index (<0.8 of heart rate
reserve at peak exercise) caused by sinus node dys-
function, medications like β−blockers, or ischemia,
are occasionally associated with increased mortality
and cardiac events even after adjusting for left ven-
tricular function and the severity of exercise-induced
myocardial ischemia.
4
e HR should decrease by at
least 12 beats in the first minute of recovery, which
is mediated through vagal reactivation. Otherwise,
recovery is considered abnormal, which has a bad
prognosis, with a 6-year mortality 2-3 times greater
than those with normal recovery.
4,5
BP should increase by at least 10 mm Hg during
exercise except in patients on antihypertensive treat-
ment where a blunted response is observed. Diastolic
blood pressure (DBP) exhibits little or no change
(<10 mm Hg) during exercise because of peripheral
vasodilatation. A sustained drop of SBP>10 mm Hg,
confirmed within 15 seconds, often indicates severe
left ventricular dysfunction and severe CAD and is
an indication to stop the test immediately and re-
fer for further evaluation and treatment (Table 2).
Failure to increase systolic blood pressure by 10 to
30 mm Hg during exercise testing is an independent
predictor of adverse outcome in patients after myo-
cardial infarction.
6
However, it is crucial to exclude
other causes that could cause a drop in SBP with
exercise without the presence of severe CAD or left
ventricular dysfunction, i.e. vasovagal syncope, cardi-
ac arrhythmias, left ventricular outflow obstruction
or hypovolemia. In addition, an abnormal BP recov-
ery, defined by the SBP at 3 minutes of recovery over
an SBP at 1 minute of recovery >1, is associated with
a greater likelihood of severe angiographic CAD.
7
An abnormal rise of SBP to a level > 214 mm
Hg in patients with a normal resting BP predicts an
increased risk for future sustained hypertension, esti-
mated at approximately 10% to 26% over the next 5
to 10 years.
8
However, in adults evaluated for CAD,
exercise hypertension is associated with a lower like-
lihood of angiographically severe disease and a lower
adjusted mortality rate on follow up.
9
Table 1. Common indications and contraindications for exercise stress testing.
Indications
• Evaluating the patient with chest pain or dyspnea with other findings suggestive,
but not diagnostic of coronary artery disease (CAD)
• Risk stratification post-myocardial infarction
• Determining prognosis and severity of coronary artery disease
• Evaluating the effects of medical and surgical therapy
• Screening for latent coronary disease
• Evaluation of congestive heart failure
• Evaluation of arrhythmias
• Evaluation of functional capacity and formulation of an exercise prescription
• Evaluation of congenital heart disease
• Stimulus to a change in lifestyle
Contraindications (absolute)
• Very recent MI, < 3-4 days
• Unstable angina, not previously stabilized by medical therapy
• Severe symptomatic left ventricular dysfunction
• Life threatening dysrhythmias
• Severe aortic stenosis ( relative?)
• Acute pericarditis, myocarditis or endocarditis
• Acute aortic dissection
Contraindications (relative)
• Left main coronary stenosis
• Moderate stenotic valvular heart disease
• Electrolyte abnormalities
• Severe arterial hypertension (SBP>200 mmHg or DBP>110 mmHg)
• Tachyarrhythmias or bradyarrhythmias
• Hypertrophic cardiomyopathy and other forms of outflow tract obstruction
• Mental or physical impairment leading to inability to exercise adequately
• High-degree atrioventricular block

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Interpretation of the electrocardiogram
(ECG)
ST changes should be read at 60 to 80 ms from the
J point,
16
and the test should be considered positive
for ischemia if there is a 2 mm or more rapidly up-
sloping ST depression (when the slope is more than
1 mV/s) ,
17,18
a 1.5 mm or more slowly up-sloping
ST depression (when the slope is less than 1 mV/s)
(Figure 1), or a 1 mm or more horizontal or down
sloping ST depression (Figure 2, 3).
Ischemic ST-segment changes developing dur-
ing recovery from treadmill exercise in apparently
healthy individuals has adverse prognostic signifi-
cance similar to those appearing during exercise.
Resting ST-segment depression has been identified
as a marker for adverse cardiac events in patients
with and without known CAD.
19,20,21,22
Diagnostic
end points of 2 mm of additional exercise-induced
ST-segment depression or downsloping depression
of 1 mm or more in recovery were particularly use-
ful markers in these patients for diagnosis of any
coronary disease (likelihood ratio 3.4, sensitivity 67
percent, specificity 80 percent).
22,23,24
Factors that
preclude or interfere with proper interpretation of
ECG are listed in Table 3.
In a recently published study, after 23 years of fol-
low up, patients with frequent ventricular ectopy (a
run of 2 or more consecutive premature ventricular
contractions (PVC) making up more than 10% of
all PVCs on any 30 seconds ECG) had an increased
risk of death from cardiovascular causes by a fac-
tor of 2.5 times, similar to that observed in patients
who had a positive ischemic response to exercise.
Frequent PVCs at rest or during recovery were not
associated with an increase in cardiovascular mortal-
ity in this study, but in another study a stronger as-
sociation between ventricular ectopy during recovery
and increased 5-year mortality was noted.
25
Exercise-induced right bundle branch block
(RBBB) or left bundle branch block (LBBB) is usu-
ally considered nonspecific unless it is associated
with evidence of ischemia, i.e. angina, and then it
is strongly suggestive of ischemia. Causes for a false
positive test include left ventricular hyprtrophy
(LVH), which is associated with decreased exercise
testing specificity, but sensitivity is unaffected.
26
Digitalis causes exercise-induced ST depression in
25% to 40% of normal subjects.
27,28,29
Other diseases
that might cause a false positive test include mitral
or aortic valve dysfunction or mitral valve prolapse,
pulmonary hypertension, pericardial constriction,
hypokalemia, glucose ingestion prior to the test and
Figure 3. Down-sloping ST depression.
Figure 2. Horizontal ST depression.
Figure 1. Slowly up-sloping ST
depression.
in females during reproductive
years.
Causes of false negative test
include use of β-blockers, which
may reduce the diagnostic or
prognostic value of exercise test-
ing because of inadequate heart
rate response, but the decision to
remove a patient from β-blocker
therapy for exercise testing should
be made on an individual basis
and should be done carefully to
avoid a potential hemodynamic
“rebound” effect, which can lead
to accelerated angina or hyperten-
sion.
28,30
Acute administration of
nitrates can attenuate the angina
and ST depression associated
with myocardial ischemia. Atrial
repolarization waves are opposite
in direction to P waves and may
extend into the ST segment and T
wave. Exaggerated atrial repolar-
ization waves during exercise can
cause downsloping ST depression
in the absence of ischemia.
31,32
e final Interpretation of the ECG is positive if
the ST criteria are met at any heart rate, and there
are no factors to preclude appropriate interpretation
of the test. e interpretation is negative if no sig-
nificant ST changes are noticed. e test is nondi-

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agnostic if the patient fails to achieve 85% of the
MPHR and the test was negative. e results are
indeterminate if the patient has baseline LBBB, a
paced rhytm, LVH with repolarization changes and/
or is on digoxin therapy. Patients with an abnormal
exercise ECG, but a normal perfusion scan have a
low risk for future cardiac events (<1%).
33
Exercise testing in women
Numerous reports have demonstrated a lower di-
agnostic accuracy for exercise electrocardiography
in women, in particular the occurrence of 1 mm of
ST segment depression. e average sensitivity and
specificity for the exercise electrocardiogram are 61%
and 69%.
34,35,36
e increased age of presentation by
women, coincident with functional impairment, is
associated with lower exercise capacity and an in-
ability to attain maximal stress. Additional critical
factors that have been reported to affect test accuracy
in women include resting ST-T wave changes in hy-
pertensive women and lower electrocardiographic
voltage and hormonal factors. For the premenopaus-
al woman, endogenous estrogen has a digoxin-like
effect that may precipitate ST segment depression,
resulting in a false positive test. Physicians who test
pre-menopausal women with chest pain or estab-
lished coronary disease should caution the use of
exercise stress testing in a woman’s mid-cycle where
estrogen levels are highest. Reports have noted a re-
duced frequency of ischemic episodes and chest pain
during this phase of the menstrual cycle. e accu-
racy of the exercise electrocardiogram in women is
highly variable and is influenced by multiple factors,
including exercise capacity and hormonal status. e
current American College of Cardiology/American
Heart Association (ACC/AHA) guidelines
6
for
exercise testing recommend this test as a first-line
test for those with a normal resting 12-lead ECG
and for those capable of performing maximal stress.
Although maximal stress may be defined by achiev-
ing 85% of predicted maximal heart rate, care should
be taken when interpreting a woman’s heart rate re-
sponse. For deconditioned patients, a hyperexagger-
ated response to physical work may result in marked
increases in heart rate. us, the test should be con-
tinued until maximal symptom-limited exercise ca-
pacity. Women incapable of performing a minimum
of 5 METS of exercise should be considered candi-
dates for myocardial perfusion imaging with phar-
macologic stress.
Women with diabetes are a special population
worthy of mention. ey are at an increased risk for
premature atherosclerosis and at significant risk for
myocardial infarction and cardiac death. e unique
pathophysiology of diabetes mellitus makes tradi-
tional symptoms less reliable and diagnosis of CAD
more challenging. e ECG is often a less reliable
indicator of significant CAD in the diabetic patient.
Myocardial perfusion imaging has been shown to be
accurate in the risk assessment and prediction of fu-
ture cardiac events in the diabetic woman.
Stress testing following myocardial infarc-
tion (MI)
Exercise stress testing is an invaluable tool for risk
stratification post-MI. In the early days post MI
(days 3-7), a low level stress test limited to 5 METS,
Table 3. Factors that preclude interpretation of exercise stress testing results.
• Left bundle branch block
14
• Left venticular hypertrophy with repolarization changes
• Digoxin therapy
• Right bundle branch block, cannot interpret leads V1-V3
15
• Marked ST abnormalities at baseline with ST depression > 1 mm in at least two
leads
• Paced ventricular rhythm
• Preexcitation syndrome (Wolff-Parkinson-White)
Table 2. Indications for early termination of exercise stress testing
• Hypotension, with SBP drop > 10 mmHg
• Ventricular or Supraventricular arrhythmias other than PVC’s or PACs
• Severe Hypertension, SBP >250 or DBP >120 mmHg
• ST elevation (> 1mm in leads without Q waves), if transient, often indicate severe
proximal coronary stenosis and ominous prognosis
10,11,12,13
• Angina with dynamic ST changes
• Excessive ST Depression, > 2 mm horizontal or downsloping
• Signs of poor perfusion, i.e. pallor or cyanosis
• Achieving 100% of MPHR
High-risk criteria:
• Hypotension with systolic BP drop > 20 mm Hg
• Early positivity, within the first or second stage of the Bruce protocol
• Late recovery
• Diffuse ST-T changes
• More than 2 mm ST depression in multiple leads
• ST elevation
10,11,12,13

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75% of MPHR or 60% of MPHR on β−blockers, is
very helpful in patients who were treated conserva-
tively with no revascularization to assess for ischemia
at low workload, arrhythmias, to start cardiac reha-
bilitation and gaining self confidence. Late post-MI
(4-6 weeks), symptom limited stress testing is usu-
ally performed to assess revascularization, medical
therapy or need for any further intervetions.
EKG interpretation with pharmacologic
stress testing
e same criteria in exercise stress testing applies,
but the sensitivity of an adenosine and dipyridam-
ole pharmacologic stress EKG is much lower than
exercise stress testing (30% vs. 65% respectively).
However, specificity (95% vs. 85% respectively) and
PPV (90%) is much higher than exercise stress test-
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37,38
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39,40
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