Ebook Dynamic echocardiography: Part 2

Section VI
Coronary Artery Disease


VI

Chapter

41

Stress Echocardiography in
Chest Pain Syndromes
Hector R. Villarraga, MD, FASE

Ischemic heart disease (IHD) remains the leading cause of
death in the United States and is the principal contributor to
the nation’s morbidity and health care expenditures. Cigarette
smoking, physical inactivity, obesity, hypertension, and metabolic syndrome also contribute to the high IHD incidence
rates among both women and men. More than a quarter of
a million women die each year in the United States from
IHD and its related conditions, and current projections indicate that this number will continue to rise with our aging
population.1
The evaluation of IHD in women presents a unique and
sometimes difficult challenge for clinicians because of the
greater symptom burden and lower prevalence of angiographically significant coronary artery disease (CAD) in women
compared with men.1 There are gender differences in the type,
frequency, and quality of symptoms of CAD.2
In a patient with a chest pain syndrome, the history, including the presence or absence of conventional risk factors, the
physical examination, and the electrocardiogram (ECG) are
important factors to consider. A noninvasive diagnostic stress
test frequently is selected to evaluate for the presence of significant CAD, to discriminate between significant and nonsignificant disease, and to predict prognosis.

Diagnostics
Exercise Electrocardiographic Evaluation
The evidence suggests that one should not rely on the exercise
ECG alone for diagnostic purposes in the detection of CAD
because it is imprecise and has lower accuracy than other
diagnostic methods, especially in women. Even when exercise
stress test risk scores such as the Duke treadmill score are
incorporated into the diagnostic method, exercise electrocardiography remains inferior to diagnostic imaging tests, such
as exercise echocardiography.3

Exercise Echocardiography
Exercise echocardiography combines treadmill or bicycle
exercise with ultrasound imaging of the heart with the goal of
detecting stress-induced wall motion abnormalities.
Before exercise, the resting echocardiographic images are
obtained from the parasternal and apical windows.4 These
standard images include parasternal long-axis, parasternal
188

short-axis, apical four-chamber, apical long-axis, apical twochamber, and apical short-axis views. In cases when the parasternal window is suboptimal, the subcostal approach can be
used. The apical short-axis view proves particularly useful for
assessing the presence or absence of apical regional wall
motion abnormalities because, in some patients, visualization
of the apex can be incomplete or foreshortened in the standard apical views. Inferior basal wall motion abnormalities
may be difficult to interpret; an abnormality in this region
should be documented in two different views, including the
basal short-axis view or assessment of the basal inferior
septum, which usually has the same coronary vascular supply.
Once the patient exercises, images are acquired in the same

format as during the rest acquisition and ideally are completed
within 1 minute after exercise (treadmill) or during peak exercise (bicycle). Acquisition of the postexercise images is challenging because of lung and motion artifacts as well as a
limited time window after exercise; however, with the current
imaging equipment, the use of harmonics, and occasionally
the use of contrast agents, feasibility is excellent.5 The digitized
images are displayed side-by-side for comparison with the
resting images. Continuous tape recording of all stress images
is recommended as a backup. In our laboratory, this information is also reviewed.

Analysis of the Exercise Echocardiogram
In addition to the global and regional left ventricular response
to stress, the adequacy of workload achieved and the presence
of symptoms or ECG changes should be considered. The additional information obtained from the echocardiogram at rest
and immediately after exercise increases the sensitivity and
specificity of this diagnostic modality.
The interpretation of the echocardiographic study should
include semiquantitative scoring of each of the segments of
the left ventricle at rest and with stress, as previously described.4
The left ventricle is divided into 16 segments (or 17 segments
if the apical cap is included) (Fig. 41.1). Each segment is analyzed individually and scored on the basis of its motion and
systolic thickening as follows: 1 = normal or hypercontractile;
2 = hypokinetic, 3 = akinetic; 4 = dyskinetic, 5 = aneurysmal;
or “not seen.” By dividing the sum of the scores by the total
number of segments analyzed, a global left ventricular wall
motion score index, both at rest and at exercise, can be generated. Myocardial ischemia is diagnosed when the postexercise


Section VI—Coronary Artery Disease

Fig. 41.1 The model for semiquantitative segmental evaluation of
regional wall motion of the left
ventricle is represented. The basal
inferoseptum and inferior wall and
mid-inferior wall are attributed to
the right coronary artery, the
anteroseptum and anterior wall to
the left anterior descending coronary artery, the anterolateral wall to
the left anterior descending or circumflex, and the inferolateral wall
to the right coronary artery or circumflex. The apical cap (seventeenth segment) is attributed to the
left anterior descending coronary
artery.

1 4 chamber
4
5
6
3

2

Apical cap
Apical
Apical
lateral
septum
Mid
Mid
anterolateral

inferoseptum
Basal
Basal
inferoseptum anterolateral

2 chamber

Apical cap
Apical
Apical
inferior
anterior
Mid
Mid
inferior
anterior
Basal
inferior

Basal
anterior

3

189

Long axis

Apical cap
Apical

Apical
lateral
anterior
Mid
Mid
inferolateral
anteroseptum
Basal
Basal
inferolateral
anteroseptum

2
1
4 Base

5 Mild

Anterior
Anteroseptum

Anterolateral

Inferoseptum
Inferior

Inferolateral

Anterior
Anteroseptum

Inferoseptum
Inferior

6 Apex
Anterolateral
Inferolateral

Anterior
Septal

Lateral

Inferior

echocardiographic images document a new regional wall
motion abnormality or when no hyperdynamic motion develops despite a good exercise work load.
The cardiologist interpreting the results of the test must
analyze the images in a thorough and methodical fashion. In
addition to assessing the segmental responses to stress, the
global left ventricular response to stress also must be considered. Normally, the ejection fraction will increase and the left
ventricular end systolic volume will decrease in a normal
study.4

Types of Exercise Protocols
Cycle
Ideally the cycle should vary the resistance to the pedaling
speed, allowing better power output controls, because it is
common for uncooperative or fatigued subjects to decrease
their pedaling speed. Cycles are calibrated in kilopods or
watts. Cycle ergonometry is usually less expensive and requires

less space than a treadmill (Fig. 41.2). Compared with treadmill exercise, upper body motion is usually reduced, making
it easier to obtain blood pressure measurements and to record
the ECG. When subjects with angina perform identical submaximum cycle work in the supine and upright positions,
heart rate is higher in the supine position, maximum work
performance is lower, and angina develops at a lower double
product. A major limitation to cycle ergometer testing is the
discomfort and fatigue of the quadriceps muscles. Normal
protocols for exercise testing include initial warm-up (low
load) and progressive uninterrupted exercise with increasing
loads, an adequate duration in each level, and a recovery
period. For cycle ergonometry, the initial power output is
usually 10 or 25 watts, usually followed by increases of 25
watts every 3 to 5 minutes until end points are reached.6

Treadmill
Subjects should not tightly grab the front or side rails because
this action decreases the workload and increases the exercise
time and muscle artifact. Several different treadmill protocols

Fig. 41.2 Supine bicycle exercise echocardiography is illustrated. The
patient pedals a cycle ergometer attached to a specially designed bed.
Echocardiographic imaging is performed at rest and during exercise.

are in use; the most commonly used is the Bruce protocol. The
patient of average height may be instructed that the first three
stages involve walking and that the fourth stage involves either
running or walking. It is important to adjust or select the
treadmill or cycle ergometer and protocol to the subject being
tested. The optimal protocol should last between 6 and 12
minutes, and the exercise capacity should be reported in metabolic equivalents (METs) and minutes.6

Accuracy of Exercise Stress
Echocardiography in Women
Exercise stress echocardiography has reached a state of maturity not only with data regarding its sensitivity and specificity
but with outcome and prognosis as well. The mean sensitivity
of exercise echocardiography in general is 84% with a specificity of 87%; in women the sensitivity ranges from 77% to 88%
with a mean weighted specificity of 73%.5
Multiple studies have evaluated outcome and prognosis
with respect to cardiac death and cardiovascular events. In a


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Section VI—Coronary Artery Disease

study of 5798 consecutive patients7 with known or suspected
CAD that included 2476 women with a mean age average of
62 ± 12 years who were monitored for 3.2 ± 1.7 years, the 1-,
3- and 5-year survival rates for women and men with a negative test were 99.8%, 99.2%, and 97.6% and 99.5%, 98%, and
96.7%, respectively. For cardiac events, the event-free survival
rates for women and men were 99.5%, 97.6%, and 94.9% and
99.5%, 98.0% and 96.7%, respectively, for 1, 3, and 5 years.7
In patients with a normal exercise echo who exercise satisfactorily (more than 5 METs for women and more than 7 METs
for men), the cardiac event-free survival rates at 1, 2, and 3
years were 99.2%, 97.8%, and 97.4%, respectively.8 Thus the
outcome after a normal exercise echocardiogram is excellent,
with an event rate of <1% per person year of follow-up. In a
recent meta-analysis, the negative predictive value was 98.4%
in women and 96% in men during an average of 38 months
of follow-up, which corresponded to annualized event rates

of 0.75% in women and 1.24% in men.9

Summary
CAD remains the leading cause of death in women. Exercise
echocardiography has been shown to provide a higher sensitivity and specificity as well as incremental prognostic value
compared with the exercise ECG. The outcome of a patient
who exercises satisfactorily and has a normal exercise echocardiogram is excellent.

References
1.American Heart Association: Heart disease and stroke statistics (website):
/>date.pdf. Accessed January 15, 2004.
2. Leslee J, Shaw C, Merz NB, et al: Insights from the NHLBI-sponsored
women’s ischemia syndrome evaluation (WISE) study, Part I: gender
differences in traditional and novel risk factors, symptom evaluation, and
gender-optimized diagnostic strategies. J Am Coll Cardiol 47:S4-S20, 2006.
3.Peteiro J, Monserrrat L, Pineiro M, et al: Comparison of exercise
echocardiography and the Duke treadmill score for risk stratification in
patients with known or suspected coronary artery disease and normal resting
electrocardiogram. Am Heart J 151:1324e1-1324e10, 2006.
4. Roger VL, Pellikka PA, Oh JK, et al: Stress echocardiography, Part I: exercise
echocardiography: techniques, implementation, clinical applications, and
correlations. Mayo Clin Proc 70:5-15, 1995.
5.Agency for Healthcare Research and Quality: Diagnosis and treatment of
coronary heart disease in women: systematic reviews of evidence on selected
topics, Chapter 2: systemic review of the accuracy of exercise myocardial
perfusion imaging and echocardiography for diagnosis of coronary heart disease
in women (AHRQ publication No. 03-E037):. />downloads/pub/evidence/pdf/chdwomtop/chdwmtop.pdf.
6. Fletcher GF, Balady G, Froelicher VF, et al: Exercise standards: a statement
for healthcare professionals from the American Heart Association.
Circulation 86:340-344, 1992.

7.Arruda-Olson AM, Juracan EM, Mahoney DW, et al: Prognostic value of
exercise echocardiography in 5,798 patients: is there a gender difference? J
Am Coll Cardiol 39:625-631, 2002.
8. McCully RB, Roger VL, Mahoney DW, et al: Outcome after normal exercise
echocardiography and predictors of subsequent cardiac events: follow-up of
1,325 patients. J Am Coll Cardiol 31:144-149, 1998.
9. Metz LD, Beattie M, Hom R, et al: The prognostic value of normal exercise
myocardial perfusion and exercise echocardiography. J Am Coll Cardiol
49:227-237, 2007.


Chapter

42

VI

Exercise Echocardiography in
Left Ventricular Hypertrophy
(and Other Pitfalls)
Thomas H. Marwick, MBBS, PhD

Overview: Current Weaknesses of
Stress Echocardiography
Stress echocardiography has been a routine stress imaging test
for nearly 2 decades but, like all noninvasive tests, its accuracy
is imperfect. Knowledge of its limitations is important in clinical decision making, and perhaps even more so as new technologies become available. We cannot hope to improve the
test without defining its limitations (Table 42.1).

Problems With Stress Echo

Interpretation With Left
Ventricular Hypertrophy
Left ventricular hypertrophy (LVH) presents a problem at
several levels when interpreting noninvasive tests for the
detection of coronary artery disease. Many patients have
hypertensive heart disease, and hypertension itself can limit
the performance of stress tests. The subendocardium in these
patients is highly susceptible to ischemia, both because it is
furthest from the coronary vessels and because it is compressed by increased LV cavity pressure. As a consequence,
false-positive electrocardiographic results are common (Figs.
42.1 and 42.2). Similarly, the reduction of coronary flow
reserve may compromise the sensitivity of myocardial perfusion imaging, and false-positive scintigraphy results also are
common. Of all the standard tests, the accuracy of stress echocardiography is probably the least influenced by LVH, with
studies attesting to its accuracy1 and documenting its superiority over scintigraphy (Fig. 42.3).2
Despite these favorable results, the interpreter must be alert
to potential pitfalls in the interpretation of these studies.
Patients with small LV cavities (often with LVH and commonly with dobutamine stress because of the vasodilator
effect of this drug) pose a particular problem. A small LV
cavity is a problem both because the endocardial circumference over which a wall motion abnormality can be detected is
reduced and because small cavity size equates to reduced wall
stress and therefore may preclude the development of isch-

emia. A small LV cavity is prognostically benign3 but may be
associated with reduced sensitivity.4 Some investigators have
recommended administering a saline solution bolus to maintain LV filling; another approach is to administer a β-blocker,
which decreases the heart rate and therefore increases LV
volumes.5 Conversely, LVH also may compromise specificity
in the setting of a hypertensive exercise response, which
increases wall stress and may cause wall motion abnormalities
in the absence of coronary stenoses.6

Other Pitfalls
Imaging Pitfalls
Despite improvements in image quality from harmonic
imaging and other technical advances, the feasibility and reliability of stress echocardiography remain heavily dependent
on image quality. The physician or sonographer must be
meticulous with image acquisition; accurate interpretation is
based on reproducing the same imaging planes (and image
depth) at each level of stress, provision of excellent endocardial detail, and satisfactory triggering. Use of LV opacification
(discussed in Chapter 53) and three-dimensional echocardiography may help overcome some of these technical issues.

Interpreter Pitfalls
Subjective assessment is a major and ongoing pitfall for
stress echocardiography, and the accuracy of the technique
depends on an expert observer. Studies of expert interpretation at different sites have shown suboptimal concordance,
especially in the setting of poor image quality or small areas
of abnormality.7 Although this problem has been reduced
by the development of standard interpretive criteria, side-byside digital display, and improved imaging, the κ value for
concordance between observers remains <0.8. Interestingly,
despite different interpreters having a different threshold
for identifying wall motion as abnormal, their overall
accuracy is not very different. The possibility of a quantitative
technique reducing this variability is discussed in another
chapter.
191


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Section VI—Coronary Artery Disease

HT PATIENT WITH ATYPICAL CHEST PAIN AND ST CHANGES DURING STRESS TESTING

Septum 13mm, PW 12mm, EDD 47mm; RWT 53%, LV mass 269g (153 g/m2)
ie Mild LVH with concentric remodeling
Fig. 42.1 In this patient with chest pain and hypertension, the exercise electrocardiogram was positive for ischemia. With exercise echocardiography,
mild concentric left ventricular hypertrophy was appreciated. The exercise echocardiogram was negative for ischemia. Parasternal images revealed a
symmetric improvement in contractility with the stress of exercise (right panels). HT, Hypertension; PW, posterior wall; EDD, end-diastolic diameter;
RWT, relative wall thickness. (From Fragosso G, Lu C, Dabrowski P, et al: Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine
stress echocardiography for the detection of coronary disease in hypertensive patients with chest pain and positive exercise test. J Am Coll Cardiol 34(2): 441-447, 1999.)

EXERCISE ECHO IS MORE SPECIFIC THAN SPECT

Table 42.1  Pitfalls of Stress
Echocardiography
Influence of LV cavity size (roles of hypertrophy and
hypertension)
■ Dependence on image quality
■ Imaging pitfalls (off-axis images, failure to use standard
depth)
■ Subjective interpretation
■ Limitations of an ischemia-based technique
■ Diagnosis of single-vessel coronary artery disease
■ Recognition of multivessel coronary artery disease
■ Recognition of ischemia within areas of abnormal resting
wall motion

pϽ0.01

pϽ0.001

pϭNS

Sensitivity

Specificity

Accuracy

100

■

80
60
40
20
0
MIBI-SPECT

Patient-Related Pitfalls
Stress echocardiography has a number of inherent weaknesses
that derive from the need to induce ischemia in order for a
study to be abnormal. These weaknesses include difficulties
in the recognition of single-vessel disease, the recognition
of multivessel disease as such, and the recognition of
ischemia within or in close proximity to resting wall motion
abnormalities.
The development of regional dysfunction requires the presence of ischemia, but the patient may undergo insufficient

DbEcho

Nϭ101 pts with HT,
57 with LVH
Fig. 42.2 In a study of 101 patients with hypertension—57 with LVH—
the specificity of stress echocardiography was superior to that of MIBISPECT for angiographic coronary artery disease. HT, Hypertension;
MIBI-SPECT, methoxyisobutyl isonitrile single-photon emission computed
tomography; DbEcho, dobutamine echocardiography. (From Fragosso G,
Lu C, Dabrowski P, et al: Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine stress echocardiography for the detection of
coronary disease in hypertensive patients with chest pain and positive exercise test.
J Am Coll Cardiol 34(2): 441-447, 1999.)


Section VI—Coronary Artery Disease


ATYPICAL CHEST PAIN AND ST CHANGES WITHOUT CAD

193

addressed by the judicious use of LV opacification, myocardial
contrast, and three-dimensional and quantitative techniques.
Patients with LVH may have both false-positive and falsenegative scans, and wall motion analysis should be integrated
with an understanding of their hemodynamic response.

References

Ongoing chest pain provoked coronary angiography, showing no
significant epicardial disease
Fig. 42.3 Because of ongoing chest pain, coronary angiography was
performed. However, no significant epicardial disease was present in this

patient, who had a false-positive result on exercise electrocardiogram.

stress to provoke ischemia, either because of the inability to
exercise maximally or because of treatment with β-adrenoceptor
blockers (other anti-ischemic agents do not seem to have
such a negative effect on sensitivity). The combination with
myocardial contrast may help reduce the impact of these
problems.

Conclusion
As with any noninvasive technique, stress echocardiography
has a number of pitfalls. Some of these pitfalls may be

1. Marwick TH, Torelli J, Harjai K, et al: Influence of left ventricular
hypertrophy on detection of coronary artery disease using exercise
echocardiography. J Am Coll Cardiol 26:1180-1186, 1995.
2. Fragasso G, Lu C, Dabrowski P, et al: Comparison of stress/rest myocardial
perfusion tomography, dipyridamole and dobutamine stress
echocardiography for the detection of coronary disease in hypertensive
patients with chest pain and positive exercise test. J Am Coll Cardiol
34:441-447, 1999.
3. Secknus MA, Niedermaier ON, Lauer MS, et al: Diagnostic and prognostic
implications of left ventricular cavity obliteration response to dobutamine
echocardiography. Am J Cardiol 81:1318-1322, 1998.
4.Yuda S, Khoury V, Marwick TH: Influence of wall stress and left ventricular
geometry on the accuracy of dobutamine stress echocardiography. J Am Coll
Cardiol 40:1311-1319, 2002.
5. Mathias W Jr, Tsutsui JM, Andrade JL, et al: Value of rapid beta-blocker
injection at peak dobutamine-atropine stress echocardiography for
detection of coronary artery disease. J Am Coll Cardiol 41:1583-1589,

2003.
6.Ha JW, Juracan EM, Mahoney DW, et al: Hypertensive response to exercise:
a potential cause for new wall motion abnormality in the absence of
coronary artery disease. J Am Coll Cardiol 39:323-327, 2002.
7.Hoffmann R, Marwick TH, Poldermans D, et al: Refinements in stress
echocardiographic techniques improve inter-institutional agreement in
interpretation of dobutamine stress echocardiograms. Eur Heart J
23:821-829, 2002.


VI

Chapter

43

Abnormal Exercise
Echocardiography in
Coronary Artery Disease
Hector I. Michelena, MD

It is common knowledge that the functional significance of a
moderate anatomic luminal obstruction (50%-70%) in an
epicardial coronary artery cannot be defined by coronary
angiography alone. In modern cardiology, the debate between
proponents of anatomy and physiology has led to the conclusion that the truth lies not in either one but in their complementary combination.1 Stress echocardiography (SE) provides
a window into the physiology of the exercising cardiac muscle,
and is capable of determining the functional impact of
obstructive coronary artery disease (CAD). For more than 15
years, SE has been recognized as a rapid, portable, versatile,

and low-cost tool in the evaluation of the patient with suspected or known CAD.2 It has excellent sensitivity and specificity not only for diagnosing the presence of CAD but as a
predictor of the anatomic location and number of significant
epicardial coronary obstructions.3-7 As our case illustrates,
digital technology has enabled an adjustable side-by-side
display of rest and stress continuous cine loops (quad screens)
for easy and reliable interpretation by the cardiologist.2 Moreover, further refinement of image quality can be obtained with
the use of microbubble contrast technology,8-10 as our case
illustrates (Fig. 43.1). The physiological data provided by
exercise SE provides a diagnostic and prognostic platform
from which to construct a patient-tailored approach in CAD
evaluation and decision making. In some cases, this process
may include anatomic verification with coronary angiography
and mechanical intervention (percutaneously or surgically) in
obstructive CAD, as illustrated by our case.

Physiologic Principle
When the luminal obstruction of an epicardial coronary
artery is >70%, there is an exponential increase in resistance
and in pressure drop across the stenosis; this degree of stenosis
proves to limit blood flow when myocardial oxygen demand
is increased (i.e., during exercise).1 An ischemic episode is
initiated by an imbalance between myocardial oxygen supply
and demand that ultimately may be manifested as angina
pectoris. This sequence of events is termed the “ischemic
cascade.” The significance of this concept resides in the fact
that it redirects the focus from the end result, angina, to the
194

underlying pathophysiologic factors that precede it. Specifically, these events include, in chronologic order, ischemia,
perfusion abnormality, diminished left ventricular compliance, decreased myocardial contractility, increased left ventricular end-diastolic pressure, ST-segment changes in the

electrocardiogram, and, occasionally, angina pectoris.1 For
that reason, an imaging technique identifies an earlier event
in that cascade and improves the sensitivity of stress testing
compared with the sensitivity achieved with the exercise electrocardiogram. With echocardiographic analysis of wall
motion both at rest and with stress, new or worsening regional
myocardial contractility induced by ischemia is detected reliably (Fig. 43.2).11 In the absence of wall motion abnormalities,
the lack of hyperdynamic motion during exercise also may
indicate ischemia, but it is less specific.11 Other adjunctive
diagnostic criteria for a positive stress echocardiogram include
left ventricular cavity dilatation and a decrease in global systolic function, as illustrated in our case with a decrease in
ejection fraction from 60% at rest to 30% after exercise.
Importantly, these adjunctive findings are especially helpful
in persons with severe CAD when exercise is used as the stress
method; these findings may be absent when dobutamine is the
stress agent, even in the presence of severe CAD.12

Diagnostic Accuracy of
Stress Echocardiography
The average values for sensitivity and specificity of SE in
detecting CAD are 85% to 87%.4 The development of nuclear
perfusion techniques preceded SE,1 so a comparison of the
diagnostic accuracy of both techniques is appropriate. Quinones et al.3 prospectively studied 289 patients evaluated for
CAD with both SE (Bruce protocol) and thallium-201 singlephoton emission computed tomography (SPECT); 112 of the
patients also underwent a coronary angiogram. Agreement
between the two techniques was 88% for classifying a test as
positive or negative and 82% for identification of specific
regions of abnormality. False-positive results occurred in one
SE patient and in four SPECT patients; specificity was 88%
for SE and 81% for SPECT. Single-vessel lesions ≥70% were
detected by either test with a sensitivity of 85%. Two- and

Section VI—Coronary Artery Disease

195

2 CHAMBER REST

2 CHAMBER STRESS

4 CHAMBER REST

4 CHAMBER STRESS



Fig. 43.1 To enhance endocardial border definition, microbubble contrast material was used in this patient undergoing stress echocardiography.
Displayed are apical four-chamber views (top) and two-chamber views (bottom). Rest images are shown on the left side and stress images on the
right side. With the stress of exercise, there is an increase in end-systolic volume and extensive regional wall motion abnormalities. The apex was
seen to enlarge and became akinetic. Extensive regional wall motion abnormalities were present.

WALL MOTION
Rest
Wall Motion Score Index 1.00
Anterior

Baseline

Normal
Hypokinesis

Akinesis
Dyskinesis
Aneurysm
S Scarred
Not Seen

Base

Mid

Apex

Posterior
Peak Stress
Stage 2

Wall Motion Score Index 2.31

Normal
Hypokinesis
Akinesis
Dyskinesis
Aneurysm
S Scarred
Not Seen

Fig. 43.2 The schematic illustrates the extent and severity of wall motion abnormalities that developed with stress. Although regional wall motion
was normal at rest, with peak stress, the apex, much of the ventricular septum, and the mid inferolateral wall became akinetic. Extensive areas of
hypokinesis also were present. This finding is consistent with significant coronary artery disease involving at least two vessels.

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Section VI—Coronary Artery Disease

three-vessel disease were detected by each technique with a
sensitivity of 86% and 94%, respectively. Both techniques
were considered excellent for the detection of CAD, with evidence that their combined use could improve the overall accuracy in some patients, although this combined technique is
rarely utilized in clinical practice. Roger et al.4 studied 150
consecutive patients undergoing SE (Bruce or Naughton protocols) and a subsequent coronary angiogram. The overall
sensitivity for detection of CAD was 91%. The sensitivity for
correctly recognizing multivessel CAD as such (≥70% obstruction of two or three vessels or ≥50% obstruction of the left
main coronary artery) was 83%. Importantly, this study
showed that information provided by SE was independent
and incremental to clinical and exercise test variables for identification of multivessel CAD. Specifically, the number of
abnormal myocardial regions identified by poststress echocardiography was additive to clinical variables (i.e., history of
previous myocardial infarction) and electrocardiographic
variables (i.e., ST-segment depression >2 mm) for identification of multivessel CAD. This finding was demonstrated in
our case, in which results of the exercise electrocardiogram
were positive (which could represent any degree of CAD) but
a large number of myocardial segments also were involved in
this patient with critical two-vessel disease (Fig. 43.2).
Regarding the predictive power of SE for localization of the
coronary artery involved, Ryan et al.5 studied 309 patients
who underwent upright bicycle SE and coronary angiography.
The overall sensitivity for the diagnosis of CAD was 91%,
and the specificity was 78%. As expected for any stress technique, the sensitivity for the detection of single-vessel disease
was significantly lower than for multivessel disease (86% vs.
95%, respectively). Accuracy was higher for lesions in the left
anterior descending and right coronary arteries (both 79%)

compared with the left circumflex artery (36%, P < .001).
Importantly, patients with left circumflex artery disease were
correctly identified as ischemic in >90% of cases, but <20%
with single-vessel left circumflex artery lesions were correctly
ascribed to the circumflex territory. Possible explanations are
a smaller amount of ischemic myocardium with circumflex
disease, decreased lateral resolution of the ultrasound system
in the evaluation of the lateral wall from apical images, and
anatomic overlap and variability. A partial solution to this
problem is grouping the right and left circumflex coronary
arteries as a single territory (i.e., inferolateral territory), with
the anterior territory representing the left anterior descending
artery.7 This way, the sensitivities become comparable between
the two territories.
Compared with nuclear perfusion SPECT, SE performance
for detection of individual diseased vessels has proved to be
similar.6 It is important to recognize the importance of the
Bayesian principles and the verification bias that can affect SE
and all stress tests.13 The positive predictive value of a test is
dependent on the pretest probability of the tested patient or
population; in a population with a lower pretest probability
and lower prevalence of CAD, the positive predictive value of
a test will be lower. Also, in clinical practice, test verification
bias or referral bias (only patients with a “positive” SE or high
pretest probability are sent to angiography) is a cause of
apparently decreased specificity and increased sensitivity.
When these determinations are debiased by statistical
methods, specificity increases and sensitivity decreases
significantly.13

Value of Contrast for
Endocardial Definition in
Stress Echocardiography
The interpretation of SE relies on the analysis of regional wall
motion. This process is affected by the quality of the echo
images, which depends on the technical expertise of the
sonographer and the characteristics of the patient imaged.
Specifically, endocardial definition (which is crucial when
determining the degree of myocardial thickening) can significantly vary from study to study. Furthermore, even with
appropriate endocardial definition, regional thickening is still
susceptible to the inherent subjectivity of the interpreter (i.e.,
there is high interobserver variability). However, excellent
agreement of regional wall motion analysis has been documented among experienced interpreters.14
Endocardial definition can be improved with the use of
gas-filled microbubble contrast, which aids in interpretation
of both regional wall motion and overall ejection fraction and
cavity size analysis. The interobserver variability in interpretation of regional wall motion also can be reduced significantly
with the use of contrast, as recently shown by Hoffmann et al.8
The use of contrast to improve endocardial definition in poor
image quality SE studies has proved to maintain the sensitivity
and specificity of these studies so they are comparable with
that of good image quality SE studies.9 In a prospective study
of 300 consecutive patients undergoing dobutamine SE,10
contrast harmonic imaging was found to be superior to
noncontrast harmonic imaging for the percentage of wall
segments visualized, image quality, and confidence of interpretation, both at rest and at peak stress. These findings were
present in all image quality subgroups; the greatest improvement was seen in patients with the poorest image quality.
Contrast should be administered in patients in whom multiple myocardial segments are not visualized at rest and in
patients in whom all segments are partly visualized but for
whom overall image quality is substandard, because the degradation of image quality that occurs at peak stress may result

in an inadequate assessment.

References
1. Michelena HI, VanDecker WA: Radionuclide-based insights into the
pathophysiology of ischemic heart disease: beyond diagnosis. J Investig Med
53:176-191, 2005.
2. Roger VL, Pellikka PA, Oh JK, et al: Stress echocardiography, part I: exercise
echocardiography: techniques, implementation, clinical applications, and
correlations. Mayo Clin Proc 70:5-15, 1995.
3. Quinones MA, Verani MS, Haichin RM, et al: Exercise echocardiography
versus 201Tl single-photon emission computed tomography in evaluation of
coronary artery disease: analysis of 292 patients. Circulation 85:1026-1031,
1992.
4. Roger VL, Pellikka PA, Oh JK, et al: Identification of multivessel coronary
artery disease by exercise echocardiography. J Am Coll Cardiol 24:109-114,
1994.
5. Ryan T, Segar DS, Sawada SG, et al: Detection of coronary artery disease
with upright bicycle exercise echocardiography. J Am Soc Echocardiogr
6:186-197, 1993.
6.Pozzoli MM, Fioretti PM, Salustri A, et al: Exercise echocardiography and
technetium-99m MIBI single-photon emission computed tomography in
the detection of coronary artery disease. Am J Cardiol 67:350-355, 1991.
7. Sawada SG, Judson WE, Ryan T, et al: Upright bicycle exercise
echocardiography after coronary artery bypass grafting. Am J Cardiol
64:1123-1129, 1989.



8.Hoffmann R, von Bardeleben S, Kasprzak JD, et al: Analysis of regional left
ventricular function by cineventriculography, cardiac magnetic resonance

imaging, and unenhanced and contrast-enhanced echocardiography: a
multicenter comparison of methods. J Am Coll Cardiol 47:121-128, 2006.
9. Dolan MS, Riad K, El-Shafei A, et al: Effect of intravenous contrast for left
ventricular opacification and border definition on sensitivity and specificity
of dobutamine stress echocardiography compared with coronary
angiography in technically difficult patients. Am Heart J 142:908-915, 2001.
10. Rainbird AJ, Mulvach SL, Oh JK, et al: Contrast dobutamine stress
echocardiography: clinical practice assessment in 300 consecutive patients.
J Am Soc Echocardiogr 14:378-385, 2001.

Section VI—Coronary Artery Disease

197

11.Oh JK, Seward JB, Tajik AJ: The echo manual, ed 3, Philadelphia, 2007,
Lippincott, Williams, & Wilkins.
12.Attenhofer CH, Pellikka PA, Oh JK, et al: Comparison of ischemic response
during exercise and dobutamine echocardiography in patients with left main
coronary artery disease. J Am Coll Cardiol 27:1171-1177, 1996.
13. Roger VL, Pellikka PA, Bell MR, et al: Sex and test verification bias: impact
on the diagnostic value of exercise echocardiography. Circulation 95:405-410,
1997.
14.Chuah SC, Pellikka PA, Roger VL, et al: Role of dobutamine stress
echocardiography in predicting outcome in 860 patients with known or
suspected coronary artery disease. Circulation 97:1474-1480, 1998.


VI

Chapter

44

Abnormal Dobutamine Stress
Echocardiography for Ischemia
(Preoperative Risk Assessment)
Christine Attenhofer Jost, MD

You are asked to evaluate a 54-year-old male patient with
severe peripheral vascular disease, insulin-dependent diabetes, and long-standing hypertension. The patient is scheduled
for a kidney transplant. He is a nonsmoker, has no history of
coronary artery disease (CAD) or heart failure, and presently
reports no cardiac symptoms. How can preoperative risk
assessment best be performed?

that which can be obtained by models of risk based on clinical
and electrocardiographic information. The value of DSE for
risk stratification has been shown for patients undergoing
major vascular surgery4-6 but also nonvascular surgery.7
During dobutamine infusion, the heart rate at which echocardiographic signs of ischemia first occur is defined as the ischemic threshold. Ischemia occurring at a low ischemic threshold
or involving an extensive area identifies patients at highest
risk.6,7

Background
The pretest likelihood of CAD in this patient is intermediate.
The identification of cardiovascular risk factors and symptoms is important in preoperative assessment.1 According to
the perioperative executive summary guidelines of 2002, this
patient is at intermediate risk for perioperative cardiac events.
Diabetes, renal insufficiency, and low functional capacity as
a result of his peripheral vascular disease predict increased

risk.2 Kidney transplantation, which is planned in our patient,
is an intermediate-risk surgical procedure with an estimated
risk of <5%.

Preoperative Risk Assessment
Cardiovascular disease is the most common cause of death
in persons with end-stage renal disease, accounting for
42% of the combined dialysis and transplant deaths in this
patient group. The high rates of serious events resulting
from CAD in patients with end-stage renal disease make
comprehensive cardiac assessment in this patient group
compulsory, especially prior to kidney and kidney-pancreas
transplantation. Guidelines recommend that noninvasive
stress tests be performed based on the patient’s estimated
risk of CAD. Myocardial perfusion studies or dobutamine
stress echocardiography (DSE) have been recommended in
patients with intermediate pretest probability of CAD who
are unable to exercise.2 A recent meta-analysis of six dia­
gnostic tests for preoperative risk stratification favored DSE
(Fig. 44.1).3
The utility of DSE for preoperative risk assessment has been
well documented. DSE results provide information beyond
198

Cardiovascular Risk Assessment in
Chronic Kidney Disease
In a recent study of 485 patients with chronic kidney disease
who were evaluated with DSE and followed for more than 2
years, the percentage of ischemic segments by DSE was an
independent predictor of mortality and improved the predictive value of the best clinical model (Fig. 44.2).8 DSE is a

cost-effective approach to the cardiac evaluation of renal
transplant patients because it poses no danger of nephrotoxicity, it has a high diagnostic accuracy, and it provides a
wealth of additional information on left ventricular hypertrophy and valvular heart disease, which are common in this
patient group. In a study on DSE in 118 renal transplant
candidates undergoing coronary angiography, abnormal
DSE results had an excellent predictive value. Cardiac tro­
ponin T levels did not predict significant CAD in this
population.9

Protocol for Dobutamine
Stress Testing
Pharmacologic stress echocardiography can be performed
with use of an inotropic agent such as dobutamine that
increases oxygen demand or a coronary vasodilator like dipyridamole or adenosine that increases myocardial blood flow,
inducing ischemia by a steal phenomenon. The most widely
used pharmacologic agent in the United States for stress echocardiography is dobutamine; its use initially was described in
1991.10


Section VI—Coronary Artery Disease


PREOPERATIVE NON-INVASIVE CARDIAC TESTING
ϭ Dipyridamole stress echo
ϭ Ejection fraction
ϭ Exercise ECG
ϭ ST analysis
ϭ Dobutamine stress echo
ϭ Dipyridamole thallium scan
100

90
80
70
Specificity

60
50
40
30

95% confidence interval

20
10
0

0

10

20

30

40
50
60
Sensitivity

70

80

90

100

Modified after Kertai et al. Heart 2003; 89:1327
and from Shouten et al. Heart 2006; 92:1866
Fig. 44.1 A meta-analysis of six diagnostic tests for preoperative risk
stratification showed dobutamine stress echocardiography to have a
good combination of sensitivity and specificity. This test was favored
compared with other preoperative testing modalities. ECG, Electrocardiograph. (From Kertai MD, Boersma E, Bax JJ, et  al: A meta-analysis comparing

199

Dobutamine is a sympathomimetic agent with predominantly β2 agonistic activity. Administration results in inotropic and chronotropic effects, an increase in cardiac output, a
decrease in peripheral resistance, and an increase in coronary
blood flow. Dobutamine has a short half-life of 2 minutes,
which is not significantly prolonged in patients with liver
or kidney failure. Dobutamine is infused in increasing doses
starting at 5 µg/kg/min up to 40 or 50 µg/kg/min; the dose
is increased every 3 minutes. Atropine in 0.3- to 0.5-mg
doses up to a total dose of 2 mg is administered intravenously
if the increase in heart rate is insufficient. The atropine
serum half-life is 3.5 hours. The dobutamine infusion is
stopped in the presence of ischemia, significant arrhythmias,
other electrocardiogram changes, intolerable symptoms,
blood pressure decrease, or if the target dose is reached.11
Dobutamine infusions using this protocol are safe and can be

performed in a private practice setting or by trained registered
nurses.12
The most common adverse effects of dobutamine include
palpitations, shivering, chest pressure, and urge to urinate.
The positive inotropic effects precede the increase in heart
rate. Contraindications for dobutamine stress echocardiography include acute coronary syndrome, unstable arrhythmias,
untreated glaucoma, or severe prostatic hypertrophy with
urinary retention.
Signs of ischemia in stress echocardiography include new
onset of hypokinesis, akinesis, or lack of increase in contractility. Cavity dilatation or a decrease in ejection fraction are
uncommon signs of ischemia during DSE.13 A normal DSE
predicts a very low likelihood of perioperative cardiovascular
events.

the prognostic accuracy of six diagnostic tests for predicting perioperative cardiac
risk in patients undergoing major vascular surgery, Heart 89:1327-1334, 2003.)

References
100

Survival (%)

80
60
40

Normal DSE
Fixed wall motion abnormality
Յ25% ischemic segments
Ͼ25% ischemic segments

20
0

0

No. at risk
203
81
108
85

1

2

3

Years
168
61
77
59

117
48
56
42

46

26
26
20

Fig. 44.2 In a study of 485 patients with chronic kidney disease who
had dobutamine stress echocardiography, survival is plotted against the
stress echocardiography results. The percentage of ischemic segments
during dobutamine stress echocardiography provided information incremental and independent of clinical data for predicting mortality over the
subsequent 3 years. (From Bergeron S, Hillis GS, Haugen EN, et al: Prognostic
value of dobutamine stress echocardiography in patients with chronic kidney
disease. Am Heart J 153:385-391, 2007.)

1. Schouten O, Bax JJ, Poldermanns D: Assessment of cardiac risk before
non-cardiac general surgery. Heart 92:1866-1872, 2006.
2. Eagle KA, Berger PB, Calkins H, et al: ACC/AHA guideline update for
perioperative cardiovascular evaluation for noncardiac surgery—executive
summary: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Committee to Update the
1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac
Surgery). Circulation 105:1257-1267, 2002.
3. Kertai MD, Boersma E, Bax JJ, et al: A meta-analysis comparing the
prognostic accuracy of six diagnostic tests for predicting perioperative
cardiac risk in patients undergoing major vascular surgery. Heart 89:13271334, 2003.
4. Davila-Roman VG, Waggoner AD, Sicard GA, et al: Dobutamine stress
echocardiography predicts surgical outcome in patients with an aortic
aneurysm and peripheral vascular disease. Am J Cardiol 21:957-963,
1993.
5. Lalka S, Sawada SG, Dalsing MC, et al: Dobutamine stress echocardiography
as a predictor of cardiac events associated with aortic surgery. J Vasc Surg
15:831-840; discussion 841-842, 1992.

6.Poldermans D, Arnese M, Fioretti PM, et al. Improved cardiac risk
stratification in major vascular surgery with dobutamine-atropine stress
echocardiography. J Am Coll Cardiol 26:648-653, 1995.
7. Das M, Pellikka PA, Mahoney DW, et al: Assessment of cardiac risk before
nonvascular surgery: dobutamine stress echocardiography in 530 patients.
J Am Coll Cardiol 35:647-653, 2000.
8. Bergeron S, Hillis GS, Haugen EN, et al: Prognostic value of dobutamine
stress echocardiography in patients with chronic kidney disease. Am Heart J
153:385-391, 2007.
9. Sharma R, Pellerin D, Gaze DC, et al: Dobutamine stress echocardiography
and cardiac troponin T for the detection of significant coronary artery
disease and predicting outcome in renal transplant candidates. Eur J
Echocardiogr 6:327-335, 2005.


200

Section VI—Coronary Artery Disease

10. Sawada S, Segar DS, Ryan T, et al: Echocardiographic detection of
coronary artery disease during dobutamine infusion. Circulation 83:16051614, 1991.
11.Pellikka P, Roger VL, Oh JK, et al: Stress echocardiography, Part II:
dobutamine stress echocardiography: techniques, implementation, clinical
applications, and correlations (see comments). Mayo Clin Proc 70:16-27,
1995.

12. Bremer ML, Monahan KH, Stussy VL, et al: Safety of dobutamine stress
echocardiography supervised by registered nurse sonographers. J Am Soc
Echocardiogr 11:601-605, 1998.
13.Attenhofer C, Pellikka P, Oh J, et al: Comparison of ischemic response

during exercise and dobutamine echocardiography in patients with left
main coronary artery disease. J Am Coll Cardiol 27:1171-1177,
1996.


Chapter

45

VI

Myocardial Viability
Sripal Bangalore, MD, MHA, and Farooq A. Chaudhry, MD, FASE

Heart failure is a leading cause of morbidity and mortality,
with a 5-year mortality rate as high as 50%, making it the
leading cause of hospitalization in patients older than 65
years.1 Coronary artery disease (CAD) is the leading cause of
heart failure, and left ventricular (LV) systolic function is an
important prognostic marker. Numerous studies have shown
that LV systolic dysfunction is a potentially reversible condition related to myocardial stunning, hibernation, or a combination of the two mechanisms. Segments that lose function as
a result of an acute ischemic insult despite the restoration of
normal perfusion are known as “stunned myocardium” (i.e.,
they have transient postischemic dysfunction) (Fig. 45.1).
Myocardial stunning results from a mismatch between coronary flow and myocardial function, and these segments
are likely to recover function spontaneously over time (Table
45.1). On the other hand, “hibernating myocardium” refers
to segments rendered dysfunctional as a result of chronic
ischemia (Fig. 45.2). Both stunned and hibernating myocardium can potentially improve their function and are collectively referred to as “viable myocardium.”2 Several observations
suggest that the hibernation and stunning may represent different spectrums of the same condition and that in some

cases, hibernation may result from repetitive stunning as a
result of repeated episodes of ischemia or from chronic
stunning.3
In patients with ischemic cardiomyopathy, 40% of patients
have improvement in ejection fraction after revascularization,4 which means that a substantial subset of patients with
ischemic cardiomyopathy who undergo revascularization
receive little clinical or prognostic benefit from revascularization. The perioperative mortality from coronary artery bypass
grafting in patients with ischemic cardiomyopathy ranges
from 5% to >30%.5 Furthermore, revascularization of nonviable myocardium has not proved to be beneficial for either
mortality6 or improvement in global LV function. In fact, in
a meta-analysis of 24 viability studies, revascularization of
patients without viable myocardium was associated with a
trend toward a higher annual mortality rate compared with
medical management alone (7.7% vs. 6.2%, P = .23).6 In contrast, revascularization of viable myocardium has been shown
to be associated with increased ejection fraction,5 decreased
congestive heart failure symptoms,5 and improved survival6
compared with those treated medically. However, patients
with viability who did not undergo revascularization had
annual mortality rates five times higher than patients with
viable myocardium who underwent revascularization.6 The
survival benefit of revascularization increases with increasing
numbers of viable segments.6 Identifying patients with isch-

emic cardiomyopathy who have viable myocardium is important because these patients benefit from revascularization.
Given the risk of revascularization, accurate identification
of viability is needed in these patients to tailor their treatment.
The likelihood that regional and global LV function will
improve after successful coronary revascularization can be
ascertained using imaging techniques that identify myocardial
viability in dysfunctional regions (Table 45.2). Currently the

methods used for predicting myocardial viability include
assessment of contractile reserve in the dysfunctional region
using low-dose dobutamine stress echocardiography (DSE),
assessment of cell membrane integrity using single-photon
emission tomography (SPECT) with thallium-201 (201Tl)
(stress-redistribution-reinjection, stress-reinjection-24 hour
imaging, or rest-redistribution imaging), and assessment of
myocyte metabolic activity using F-18 fluorodeoxyglucose
(FDG) positron emission tomography (PET). Other techniques currently being developed include myocardial contrast
echocardiography (MCE) and contrast-enhanced magnetic
resonance imaging; both hold great promise.7,8

Dobutamine Stress
Echocardiography
Rationale
Dobutamine is a synthetic catecholamine with both positive
inotropic and chronotropic effects mediated predominantly
through β1-adrenergic receptor stimulation. The principle of
DSE is based on detection of “inotropic contractile reserve”
(CR) in dysfunctional but viable myocardial segments with
dobutamine. At low doses (4-8 µg/kg/min), dobutamine is a
positive inotrope, but at doses >10 µg/kg/min, it exhibits a
positive chronotropic effect in addition to the inotropic
effect.9 To assess myocardial viability, the response to low
doses of dobutamine must be assessed. With higher doses, the
increased heart rate resulting from a chronotropic effect will
increase myocardial demand with consequent ischemia.10,11
Consequently, low-dose dobutamine is the standard protocol
used for the assessment of myocardial viability.

Protocol
Wide variation exists in the protocol used to assess viability.
The commonly used protocol involves administering dobutamine intravenously beginning at a dose of 2.5 to 5.0 µg/kg/
min and increasing by 5 to 10 µg/kg/min every 3 to 5 minutes
201


202

Section VI—Coronary Artery Disease

Table 45.1  Blood Supply and Metabolic Activity as a Determinant of Myocardial Function
Diagnosis

Coronary Flow

Myocyte Metabolism

Prognosis

Stunned myocardium

Normal

Decreased

Spontaneous recovery of myocardial
function with time

Hibernating myocardium

Decreased

Decreased

Improvement in function with
revascularization

Wall motion
abnormality
Clamp

Wall motion abnormality
during occlusion

Coronary occlusion

Coronary reperfusion
Fig. 45.1 Pathophysiologic mechanism of myocardial stunning. In
myocardial stunning, wall motion
abnormalities persist even after
establishing coronary flow. (From

Return of
function

Kloner RA, Przyklenk K, Patel B: Altered
myocardial states. The stunned and
hibernating myocardium. Am J Med
l86(suppl 1A):14-22, 1989.)

Persistent wall
motion abnormality
(despite reperfusion
and viable myocytes)

Gradual return of function
(hours to days)

Wall motion
abnormality

Atherosclerotic narrowing

Wall motion abnormality due to
chronic ischemia without infarction
Fig. 45.2 Pathophysiologic mechanism of myocardial hibernation. In
myocardial hibernation, there is wall motion abnormality due to chronic
reduced blood supply, which represents a physiologic adaptation of the
myocytes to reduced perfusion. (From Kloner RA, Przyklenk K, Patel B: Altered
myocardial states. The stunned and hibernating myocardium. Am J Med l86(suppl
1A):14-22, 1989.)

up to a maximum of 40 µg/kg/min, or until a study end point
is achieved. The end points for termination of the dobutamine
infusion typically include development of new segmental wall
motion abnormalities, attainment of 85% of age-predicted
maximal heart rate, or the development of significant adverse
effects related to the dobutamine infusion. Echocardiographic
images are acquired at baseline, with each stage of stress and

during the recovery phase. Cardiac rhythm is monitored
throughout the stress echocardiography protocol, and 12-lead
electrocardiograms and blood pressure measurements are
obtained at baseline, at each stage of stress, and during the
recovery phase.
There are four characteristic responses of dysfunctional
myocardial segments with dobutamine infusion (Fig. 45.3):
1. Monophasic (sustained) response: Improvement at a
low dose that persists or further improves at high dose;
this response indicates viable myocardium with no stenosis of the coronary artery subtending the akinetic/
hypokinetic myocardium
2. Biphasic response: Augmentation of function at a low
dose followed by deterioration at a high dose; this
response indicates the presence of viable myocardium,
but the coronary artery that supplies the myocardium
has flow-limiting stenosis


Section VI—Coronary Artery Disease



203

Table 45.2  Imaging Techniques to Detect Myocardial Viability
Imaging Technique

Definition of Viability

Measure

Disadvantages

FDG-PET

Myocardial segments with
decreased perfusion but
with intact metabolic
activity

Identifying myocyte metabolic
activity; measures viability in the
endocardium, myocardium, and
epicardium

May overestimate viability;
requires radiotracer and
equipment; low-resolution
study; no information on wall
motion or ejection fraction;
long acquisition time; cost

201

Myocardial segments with
decreased perfusion with
delayed uptake

Identifying cell membrane
integrity; measures viability in

the endocardium, myocardium,
and epicardium

May overestimate viability;
involves radio tracer; low
resolution; cost

DSE

Wall motion abnormality
at rest that improves with
low-dose dobutamine
infusion

Identifying inotropic contractile
reserve; measures viability in the
endocardium and inner
myocardium

May underestimate viability;
subjective interpretation;
limited by poor acoustic
window

MRI

Delayed enhancement
(5-20 min) indicates
fibrosis or scar

Identifying stunned myocardium

Cost; not portable

Tl-SPECT

MRI, Magnetic resonance imaging.

RESPONSE TO DOBUTAMINE
Baseline

Low Dose

Peak

Recovery

Biphasic

Viable

Monophasic
Fig. 45.3 Response to dobutamine
during stress echocardiography.
Varying response of the myocardium to different doses of dobutamine in segments with and without
viability.

Scar

Non Phasic

3. Ischemic response: Worsening of function, without
contractile reserve; this response indicates stressinduced ischemic myocardium due to flow-limiting
stenosis (ischemia)
4. Nonphasic response: No change; this lack of response
indicates scarred myocardium with no viability
A contractile response to dobutamine requires at least 50%
viable myocytes in a given segment and correlates inversely
with the extent of interstitial fibrosis on myocardial biopsy.12
Atropine may be given with dobutamine to enhance the diagnostic value of the technique.13 Other recent techniques to
improve diagnostic yield of DSE include combining it with
MCE14 and strain rate imaging with tissue Doppler.15 Admin-

istration of nitroglycerin as an adjunct to dobutamine
may enhance accuracy for detection of hibernating
myocardium.16

Prognostic Value
The identification of myocardial viability by low-dose DSE is
of prognostic significance in patients with ischemic cardiomyopathy. In a study by Chaudhry et al.,17 the prognostic implications of myocardial CR was evaluated in patients with CAD
and LV dysfunction (ejection fraction ≤40%). In patients
undergoing medical therapy alone, those with CR (identified
by low-dose DSE) had a better initial survival rate compared


204

Section VI—Coronary Artery Disease

with those without CR, but this advantage was not maintained

beyond 3 years. In patients undergoing revascularization,
those with CR had better survival rates than did those without
CR (Fig. 45.4). By multivariate analysis, the number of dysfunctional segments demonstrating CR was the strongest predictor of survival. Thus, myocardial viability as determined by
low-dose DSE is a significant predictor of survival in patients
with CAD and LV dysfunction undergoing either medical
therapy or revascularization, independent of symptoms, baseline LV function, or coronary anatomy (see Fig. 45.4).17
The usefulness of low-dose DSE in the prediction of
improvement in regional contractile function following
revascularization has been assessed. Cusick et al.18 evaluated
the utility of DSE in patients with severe LV dysfunction
and showed similar accuracy (Fig. 45.5). Pooled analysis of
studies show that low-dose DSE has a good sensitivity (81%)
and specificity (80%) for the prediction of improvement
of regional and global LV function following revasculari­
zation.19 It thus has a good positive predictive value (77%)
100

% Survival

80

CR ϩ Revasc

60
CR ϩ No Revasc
No CR ϩ No Revasc

40
20

No CR ϩ Revasc

0
0

12

24

36

and an excellent negative predictive value (85%) (Figs. 45.6
and 45.7).19
Prior studies evaluated the presence of viability in a binary
fashion. However, Afridi et al.20 evaluated the prognostic
value of varying responses to dobutamine infusion (monophasic, biphasic, ischemic, and nonphasic responses). A
biphasic response had the highest predictive value (72%), followed by ischemia (35%), whereas the lowest predictive value
was observed in segments with either nonphasic (13%) or
monophasic response (15%) during dobutamine. Combining
biphasic and ischemic responses resulted in a sensitivity
of 74% and specificity of 73% (Fig. 45.8). Dobutamineresponsive wall motion was most often detected at doses of
5 or 7.5 µg/kg/min, and worsening usually was seen at doses
>20 µg/kg/min, although it was seen in some patients as
early as a 7.5 µg/kg/min dose. These data underscore the
Sensitivity
100
90
80
70
60

50
40
30
20
10
0

Months
Fig. 45.4 Myocardial viability and response to treatment. In patients with
left ventricular dysfunction and coronary artery disease, those with contractile reserve who underwent revascularization had the best prognosis.
CR, Contractile reserve. (From Chaudhry FA, Tauke JT, Alessandrini RS, et  al:
Prognostic implications of myocardial contractile reserve in patients with coronary
artery disease and left ventricular dysfunction, J Am Coll Cardiol 34:730-738,
1999.)

EF Ͻ 30%
84%

NPV

69

86

81
66

59

71

77

81 80

71

85
77

58

57
50

Thallium Tc SPECT
Reinjection

DSE

FDG-PET

Fig. 45.6 Sensitivity, specificity, positive predictive value, and negative
predictive value of the different imaging techniques in predicting functional recovery after revascularization. Dobutamine stress echocardiography had the best specificity and positive predictive value. PPV, Positive
predictive value; NPV, negative predictive value; Tc, technetium. (Adapted
from Bax JJ, Poldermans D, Elhendy A, et  al: Sensitivity, specificity, and predictive
accuracies of various noninvasive techniques for detecting hibernating myocardium, Curr Probl Cardiol 26:147-186, 2001.)

100

78%

90

80%
Sensitivity

Functional recovery %

100%

EF Ն 30%

83

80

Thallium
SPECT

48

PPV

93

88

86

Specificity

60%
40%
20%

61

22%

23

80
LDDE
70

FDG PET

20%

39

36
50

0%
ϩCR ϪCR

ϩCR ϪCR

Fig. 45.5 Assessment of myocardial viability in patients with severe left
ventricular dysfunction. The predictive accuracy of dobutamine stress
echocardiography for functional recovery after revascularization was
maintained in patients with or without severe left ventricular dysfunction. CR, Contractile reserve; EF, ejection fraction. (Adapted from Cusick
DA, Castillo R, Quigg RJ, et  al: Predictive accuracy of dobutamine stress echocardiography for identification of viable myocardium in patients with severely reduced
left ventricular ejection fraction, J Heart Lung Transplant 15:186S, 1997.)

99mMIBI
Tc99m
MIBI

95% Confidence
Intervals

60

TI201r-r
TI201s-r-r

0

10

20

30

40

50

60

70

80

90

Specificity
Fig. 45.7 Sensitivity and specificity of the different imaging techniques
in predicting functional recovery after revascularization. Dobutamine
stress echocardiography had the best specificity. LDDE, Low-dose dobutamine stress echocardiography. (From Bax JJ, Wijns W, Cornell JH, et al:
Accuracy of currently available techniques for prediction of functional recovery
after revascularization in patients with left ventricular dysfunction due to chronic
coronary artery disease. J Am Coll Cardiol 30(6):1451-1460, 1997.)


Section VI—Coronary Artery Disease


Recovery

87

85

90
80

None

No Recovery

72

20

50
30

28

35

15
15

20

10
13

10
0

35

25

60
40

Ͼ6 Viable Seg

30

65

70

2 to 5 Viable Seg

205

5
0

Biphasic

Ischemia

Monophasic

Non Phasic

EF Change

Event Rate

Fig. 45.8 Response to dobutamine predicts recovery of left ventricular
function after revascularization. Patients with biphasic response (which
represents both ischemia and viability) had the best recovery of function
after revascularization, emphasizing the need to continue dobutamine
infusion until the end point is reached for assessment of viability. (Adapted

Fig. 45.9 Importance of amount of viable myocardium to predict
improvement in ejection fraction and cardiovascular outcomes. The
degree of improvement in ejection fraction increased with increasing
number of viable segments and correlated with decrease in cardiac event
rate. EF, Ejection fraction. (Adapted from Meluzin J, Cerny J, Frelich M, et  al:

from Cornel JH, Bax JJ, Elhendy A, et al: Biphasic response to dobutamine predicts
improvement of global left ventricular function after surgical revascularization in
patients with stable coronary artery disease. J Am Coll Cardiol 31:1002-1010,
1998.)

Prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction,
J Am Coll Cardiol 32:912-920, 1998.)

complex nature of dobutamine responsiveness that must be
considered when interpreting clinical viability studies that use
dobutamine echocardiography. Dobutamine should be started
at a low dose with slow increments for optimal results.21
However, a test for viability should not be terminated after
use of low doses of dobutamine if it is safe to continue testing
at higher doses, because the demonstration of CR and inducible ischemia in the same segment (biphasic response) is
fairly definitive proof that the segment will improve with
revascularization.21
Other studies have evaluated the “amount” of viable myocardium as a prognostic marker. In a study by Meluzin et al.,22

persons with a large amount of viable myocardium (six or
more segments) had a greater percentage increase in ejection
fraction and a lower cardiac event rate during a mean followup of 20 months compared with patients with a modest
amount of viable myocardium (two to five segments) or no
viable myocardium (Fig. 45.9).22

Comparison With Other Modalities
Compared with other techniques for the prediction of functional recovery after revascularization, low-dose DSE has
comparable sensitivity with very good specificity (see Figs.
45.6 and 45.7).19 Bax et al.,19 in a pooled analysis of studies,
showed that the highest sensitivity was observed for FDGPET, followed by the other nuclear imaging techniques,
whereas the lowest sensitivity was observed for DSE. However,
the specificity was highest for DSE, followed by FDG-PET and
nuclear SPECT, whereas the lowest specificity was observed
for 201Tl reinjection. Thus the highest negative predictive value
(NPV) was observed for FDG-PET, followed by DSE, followed
by the other nuclear imaging techniques. Whereas the highest
positive predictive value (PPV) for recovery of segmental wall
motion abnormality was observed for DSE, followed by
FDG-PET and 201Tl rest-redistribution, the lowest PPV was
observed for 201Tl reinjection (see Figs. 45.6 and 45.7).19

Thallium Scintigraphy
Arnese et al.23 evaluated the predictive value of poststress reinjection thallium SPECT imaging and dobutamine echocardiography in 38 patients with severe LV dysfunction. Segments
that had akinesis or severe hypokinesis were examined for
improvement in function 3 months after coronary artery
bypass surgery, as assessed by regional wall thickening on
echocardiography. Thallium scintigraphy detected three times
the number of viable segments as did low-dose dobutamine
echocardiography (103 vs. 33 segments), with a higher sensitivity for an improvement of segmental function (89% for

thallium SPECT and 74% for echocardiography). Low-dose
dobutamine echocardiography, however, had a higher specificity and PPV (95% and 85%, respectively) than did thallium
reinjection imaging (48% vs. 33%, respectively).
Pooled analysis from various studies has shown that DSE
has a higher specificity, yielding a 14% higher PPV compared
with thallium SPECT.24 However, the sensitivity of thallium
SPECT is reported to be higher, yielding a 9% higher NPV
than that for DSE.24 This seems to suggest that that many
myocardial segments with baseline systolic dysfunction will
manifest thallium uptake but lack inotropic reserve during
dobutamine administration, resulting in “overestimation” of
viability by nuclear SPECT (Table 45.2).

F-18 Fluorodeoxyglucose Positron
Emission Tomography
Pierard et al.25 evaluated 17 patients after thrombolytic therapy
for acute myocardial infarction by low-dose dobutamine
echocardiography and PET imaging with FDG. Repeated
imaging 9 ± 7 months later was performed to assess the ability
of these studies to predict recovery of regional function. PET
and dobutamine echocardiography were concordant regarding the presence and absence of viability in 62 of the 78 myocardial segments (79%). However, among the segments with
discordant results by the two modalities, seven (16%) with
viability on DSE had no viability based on PET study, and


206

Section VI—Coronary Artery Disease

among the segments considered without viability on the

dobutamine study, nine (26%) had PET evidence of viability.
At the follow-up examination, the regions with viability by
both PET and dobutamine echocardiography improved in
function, and the regions with concordance regarding absence
of viability by the two techniques had persistent dysfunction.
However, all nine of the discordant regions thought to be
viable by PET but without contractile reserve did not improve
in function, and six had metabolic evidence of necrosis on the
follow-up study; among the seven regions predicted to be
viable by echocardiography but necrotic by PET, five had
improved function and normal metabolism on the follow-up
study. Thus, although PET and dobutamine echocardiography provided concordant findings in the majority of regions,
these data indicate that PET might overestimate the presence
and extent of viability and that dobutamine echocardiography
had at least similar negative predictive value and better positive predictive value than did PET for functional recovery after
thrombolytic therapy.

Reasons for Discordant Findings
Between Various Modalities to
Assess Viability
Studies such as those previously described indicate that a
greater number of dysfunctional myocardial segments have
been identified as viable by PET/nuclear than by echocardiography, indicating that some regions of viable myocardium are
metabolically active and/or have intact cell membrane but
lack inotropic reserve. The regions with discordant findings
between the two techniques tend to be those in which blood
flow is reduced at rest and those that presumably are
hibernating.
Discrepancies between dobutamine echocardiography and
SPECT or PET imaging may reflect the underlying alternations in cellular metabolism, membrane integrity, and myocyte

function. Blood flow and flow reserve may be reduced to such
an extent that contractile reserve is lost but transmembrane
pump activity is preserved. This situation could be imaged
directly with thallium or sestamibi or could be assessed by
investigating the metabolic processes necessary to generate the
high-energy processes to maintain membrane integrity. In
such cases “viability” may be detected by PET or SPECT and
not by DSE.
On the other hand, data of other investigators have shown
that the magnitude of regional perfusion-tracer activity
reflects the mass of viable tissue, which in turn correlates with
systolic function. The “overestimation” of viability with techniques such as rest-redistribution thallium scintigraphy or
PET imaging with FDG may be a result of the detection of
small regions of viability that are of inadequate size to permit
improvement in regional or global systolic function. The distribution of viable cells also MAY be important, especially
with regard to the recovery of ventricular function. A heterogeneous admixture of necrotic and viable cells may not demonstrate improved contraction, in spite of the presence of
adequate metabolic function in at least some of the cells.
However, even without the return of cardiac function, the
presence and maintenance of viability may be crucial for longterm prognosis, perhaps by the prevention of infarct expan-

sion, ventricular remodeling, and the development of heart
failure.

Future Advances
Nitroglycerin Dobutamine
Stress Echocardiography
Ling et al.16 compared nitroglycerin DSE with intracoronary
MCE and rest-redistribution 201Tl SPECT on recovery of
myocardial function following revascularization in patients
with chronic ischemic LV dysfunction. Nitroglycerin (0.4 mg)

was sprayed sublingually, followed by echocardiography
5 minutes later, followed by dobutamine infusion and standard DSE protocol. Nitroglycerin alone increased regional
thickening in 20% of viable akinetic segments. Among the
various techniques for detecting myocardial viability, nitroglycerin DSE had the best specificity, which leads to the
hypothesis that nitroglycerin may be a useful adjunct to dobutamine stimulation. Nitroglycerin has been shown to increase
contractility of viable asynergic segments by ventriculography,
enhance radionuclide uptake, and augment end-systolic wall
thickening by magnetic resonance imaging. Some of the
mechanisms that have been postulated include direct vasodilation, recruitment of collateral circulation, and optimization
of loading.

Enoximone Stress Echocardiography
Lu et al.26 evaluated the role of enoximone, a phosphodiesterase inhibitor with positive inotropic action but less hemodynamic effects compared with dobutamine, for the prediction
of functional recovery following revascularization in patients
with chronic ischemic LV dysfunction. Compared with dobutamine, enoximone echocardiography had higher sensitivity
(88% vs. 79%) and NPV (90% vs. 84%) with similar specificity (89% vs. 90%) and PPV (87% for both) for predicting
functional recovery. In patients with viable segments supplied
by critically stenotic coronary arteries, even low-dose dobutamine can induce ischemia, resulting from an increase in heart
rate and systolic blood pressure. It has been shown that enoximone does not cause much increase in heart rate and blood
pressure and hence can detect viability in critically stenotic
segments (where supply and demand are delicately balanced)
without inducing ischemia.

Strain Rate Measurement
Hoffmann et al.15 evaluated the utility of strain rate measurement for evaluation of viability in patients with LV dysfunction undergoing DSE. The peak systolic tissue Doppler velocity
and peak systolic myocardial strain rate were determined at
baseline and during low-dose dobutamine stress from the
apical views. The standard used for comparison was viability
as determined by FDG-PET. Compared with low-dose dobutamine only, strain rate measurement increased both the sensitivity (increased from 75% to 83%) and specificity (increase
from 63% to 84%) for the detection of viability. Thus strain

rate imaging may provide an important adjunct as a quantitative measure of viability, especially in identifying subtle
improvements in inotropic contractile reserve.


Section VI—Coronary Artery Disease



Myocardial Contrast Echocardiography
MCE evaluates microvascular integrity. Senior and
Swinburn27 evaluated the incremental value of MCE over DSE
at predicting recovery of function following acute myocardial
infarction. Addition of MCE to the standard DSE protocol
improved sensitivity for the prediction of improvement in
contractile function (sensitivity increased from 59% to 79%)
in dobutamine nonresponsive segments. Thus MCE may be
an important adjunct to improve the sensitivity of DSE.

Conclusions
In patients with ischemic LV dysfunction, wall motion abnormalities may be reversible (viable); presence of viability identifies regions of the left ventricle that will improve with
revascularization. DSE is a valuable technique for the assessment of myocardial viability with good sensitivity and excellent specificity even in patients with severe LV dysfunction. It
thus has a good PPV and excellent NPV for the detection of
viability. Although low-dose dobutamine is the standard protocol for assessing myocardial viability, given the prognostic
value of a biphasic response, dobutamine infusion should be
carried out to the end point whenever possible. The likelihood
of improvement of contractile function with revascularization
depends on the type of response to dobutamine (biphasic
response has the best likelihood for recovery) and the amount
of viable myocardium present. Thus DSE should be routinely
considered in patients with ischemic cardiomyopathy for risk

stratification, prognosis, and treatment.

References
1. Massie BM, Shah NB: Evolving trends in the epidemiologic factors of heart
failure: rationale for preventive strategies and comprehensive disease
management. Am Heart J 133:703-712, 1997.
2. Wu KC, Lima JA: Noninvasive imaging of myocardial viability:
current techniques and future developments. Circ Res 93:1146-1158,
2003.
3. Vanoverschelde JL, Wijns W, Borgers M, et al: Chronic myocardial
hibernation in humans: from bedside to bench. Circulation 95:1961-1971,
1997.
4. Bonow RO: The hibernating myocardium: implications for management of
congestive heart failure. Am J Cardiol 75:17A-25A, 1995.
5. Baker DW, Jones R, Hodges J, et al: Management of heart failure, III: the
role of revascularization in the treatment of patients with moderate or severe
left ventricular systolic dysfunction. JAMA 272:1528-1534, 1994.
6.Allman KC, Shaw LJ, Hachamovitch R, et al: Myocardial viability testing and
impact of revascularization on prognosis in patients with coronary artery
disease and left ventricular dysfunction: a meta-analysis. J Am Coll Cardiol
39:1151-1158, 2002.
7. deFilippi CR, Willett DL, Irani WN, et al: Comparison of myocardial
contrast echocardiography and low-dose dobutamine stress
echocardiography in predicting recovery of left ventricular function after
coronary revascularization in chronic ischemic heart disease. Circulation
92:2863-2868, 1995.
8. Kim RJ, Wu E, Rafael A, et al: The use of contrast-enhanced magnetic
resonance imaging to identify reversible myocardial dysfunction. N Engl J
Med 343:1445-1453, 2000.

207

9. Tuttle RR, Pollock GD, Todd G, et al: The effect of dobutamine on cardiac
oxygen balance, regional blood flow, and infarction severity after coronary
artery narrowing in dogs. Circ Res 41:357-364, 1977.
10. Schulz R, Rose J, Martin C, et al: Development of short-term myocardial
hibernation: its limitation by the severity of ischemia and inotropic
stimulation. Circulation 88:684-695, 1993.
11. Willerson JT, Hutton I, Watson JT, et al: Influence of dobutamine on
regional myocardial blood flow and ventricular performance during
acute and chronic myocardial ischemia in dogs. Circulation 53:828-833,
1976.
12.Nagueh SF, Mikati I, Weilbaecher D, et al: Relation of the contractile reserve
of hibernating myocardium to myocardial structure in humans. Circulation
100:490-496, 1999.
13.Poldermans D, Rambaldi R, Bax JJ, et al: Safety and utility of atropine
addition during dobutamine stress echocardiography for the assessment of
viable myocardium in patients with severe left ventricular dysfunction. Eur
Heart J 19:1712-1718, 1998.
14. Meza MF, Kates MA, Barbee RW, et al: Combination of dobutamine and
myocardial contrast echocardiography to differentiate postischemic from
infarcted myocardium. J Am Coll Cardiol 29:974-984, 1997.
15.Hoffmann R, Altiok E, Nowak B, et al: Strain rate measurement by Doppler
echocardiography allows improved assessment of myocardial viability
inpatients with depressed left ventricular function. J Am Coll Cardiol
39:443-449, 2002.
16. Ling LH, Christian TF, Mulvagh SL, et al: Determining myocardial viability
in chronic ischemic left ventricular dysfunction: a prospective comparison of
rest-redistribution thallium 201 single-photon emission computed
tomography, nitroglycerin-dobutamine echocardiography, and intracoronary

myocardial contrast echocardiography. Am Heart J 151:882-889, 2006.
17.Chaudhry FA, Tauke JT, Alessandrini RS, et al: Prognostic implications of
myocardial contractile reserve in patients with coronary artery disease and
left ventricular dysfunction. J Am Coll Cardiol 34:730-738, 1999.
18.Cusick DA, Castillo R, Quigg RJ, et al: Predictive accuracy of dobutamine
stress echocardiography for identification of viable myocardium in patients
with severely reduced left ventricular ejection fraction. J Heart Lung
Transplant 15:186S, 1997.
19. Bax JJ, Poldermans D, Elhendy A, et al: Sensitivity, specificity, and predictive
accuracies of various noninvasive techniques for detecting hibernating
myocardium. Curr Probl Cardiol 26:147-186, 2001.
20.Afridi I, Kleiman NS, Raizner AE, et al: Dobutamine echocardiography in
myocardial hibernation: optimal dose and accuracy in predicting recovery of
ventricular function after coronary angioplasty. Circulation 91:663-670,
1995.
21.Yao SS, Chaudhry FA: Assessment of myocardial viability with dobutamine
stress echocardiography in patients with ischemic left ventricular
dysfunction. Echocardiography 22:71-83, 2005.
22. Meluzin J, Cerny J, Frelich M, et al: Prognostic value of the amount of
dysfunctional but viable myocardium in revascularized patients with
coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol
32:912-920, 1998.
23.Arnese M, Cornel JH, Salustri A, et al: Prediction of improvement of
regional left ventricular function after surgical revascularization: a
comparison of low-dose dobutamine echocardiography with 201Tl
single-photon emission computed tomography. Circulation 91:2748-2752,
1995.
24. Bonow RO: Identification of viable myocardium. Circulation 94:2674-2680,
1996.
25.Pierard LA, De Landsheere CM, Berthe C, et al: Identification of viable

myocardium by echocardiography during dobutamine infusion in patients
with myocardial infarction after thrombolytic therapy: comparison with
positron emission tomography. J Am Coll Cardiol 15:1021-1031, 1990.
26. Lu C, Carlino M, Fragasso G, et al: Enoximine echocardiography for
predicting recovery of left ventricular dysfunction after revascularization.
A novel test for detecting myocardial viability. Circulation 101:1255-1260,
2000.
27. Senior R, Swinburn JM: Incremental value of myocardial contrast
echocardiography for the prediction of recovery of function in dobutamine
nonresponsive myocardium early after acute myocardial infarction. Am J
Cardiol 91:397-402, 2003.


VI

Chapter

46

Use of Tissue Doppler During
Dobutamine Stress
Echocardiography
Thomas H. Marwick, MBBS, PhD, and Manish Bansal, MD, DNB

Principles of Quantitation During
Stress Echocardiography
Among the pitfalls of stress echocardiography discussed in the
previous chapter, the most urgent issue in need of remediation remains subjective interpretation. Variations between
readers remain despite improvements in the technical aspects
of echocardiography and standard reading criteria.1 As previously discussed, a sensitive quantitative approach may not

only reduce subjectivity, but it also may enhance subtle abnormalities that are not readily apparent to the eye. Such a technique also might facilitate difficult interpretations, which may
occur if the extent of ischemia is small (e.g., mild single-vessel
disease with collaterals or multivessel disease where the main
stenosis causes limiting symptoms and may compromise recognition of other milder lesions) or if tissue does not become
sufficiently ischemic to provoke abnormal wall motion (e.g.,
insufficient stress). However, such an approach would need
to satisfy several criteria to be useful (Table 46.1).
Quantitative techniques for the measurement of regional
function have proved to be very challenging. A number of
strategies have been evaluated for the quantitation of both
radial and longitudinal function (Table 46.2 and Fig. 46.1).
Edge detection–based approaches have three major limitations: dependence on tracing the endocardial border, dependence on the timing of systole and diastole (when these are
not necessarily homogeneous), and influence by translational
movement of the heart. This chapter addresses only the tissue
Doppler–based techniques.

Principles of Tissue Doppler
Relevant to Stress
Echocardiography
Tissue Doppler is an extension of the Doppler principle to the
quantification of tissue motion rather than blood flow and can
be used to measure tissue velocity and timing. To the novice
in this area, the iterations of how these data are gathered and
processed afterward may appear bewildering. Translational
movement of tissue and tethering to adjacent segments can
208

introduce error to the measurement of these Doppler-derived
parameters. Differential motion between adjacent segments of
tissue may be identified from velocity gradients or left ventricular strain. On the other hand, signal quality is critical,

especially at peak stress, and signal noise is less of a problem
with estimation of velocity than with more complex derived
measurements, such as strain. A feasible quantitative approach
should minimize disruption to the standard study. This goal
is possible using high frame-rate color tissue data (Fig. 46.2),
and these measurements may be performed offline. Irrespective of the details, the two unique aspects to this modality are
its high signal/noise ratio and its ability to interrogate the
longitudinal (base-apex) function of the left ventricle—recognized by Leonardo da Vinci, but previously little considered
by echocardiographers!2

Stress Echocardiography With
Tissue Doppler
Tissue Doppler is well validated as a measure of myocardial
displacement. Moreover, both experimental and clinical
studies have confirmed that tissue velocity decreases in the
presence of ischemia. During stress echocardiography, tissue
velocity correlates with regional wall motion scoring; normal
myocardium shows a doubling of velocity in response to
maximal stress, with blunting of this velocity increment in
ischemic tissue and reduction of baseline velocity in infarcted
tissue.3 Tissue velocity correlates with independent markers of
ischemia such as single photon emission tomography myocardial perfusion imaging.4
Two strategies exist for the application of tissue Doppler to
stress echocardiography. The first strategy is based on the
designation of normal ranges, which is difficult because tissue
velocity is related to loading and also varies throughout the
heart. In contrast to variations in resting velocity based on
large variations of resting hemodynamics, workload is relatively more homogeneous in most patients at peak dobutamine, and neither workload nor age seem to have a major
influence on peak velocity at peak stress.5 The application of
velocity cutoffs to independent patient groups has shown a

high sensitivity and specificity for the angiographic diagnosis


Section VI—Coronary Artery Disease



209

Fig. 46.1 The various tissue Doppler
modalities that have been combined with stress echocardiography
for detection of regional abnormalities indicative of myocardial ischemia. PSS, Peak systolic strain; Pk,
peak.

TISSUE DOPPLER DURING STRESS ECHO
Importance of high frame-rate for color TDI

Sampling rate 35 f/s

Sampling rate 112 f/s

Fig. 46.2 Quantitative assessment
of segmental function using tissue
Doppler imaging (TDI) with stress
echocardiography is optimized by
using a high frames per second (f/s)
rate, as shown on the right side of
the figure.

Table 46.1  Criteria for a Quantitative

Approach to Stress Echocardiography
High feasibility (i.e., not heavily dependent on image
quality)
■ Convenient; minimal disruption/incremental time to
imaging/interpretation
■ Limited variation: interobserver/intraobserver, test-retest
■ Definable normal range suitable for most candidates

Table 46.2  Techniques for the Quantitation
of Regional Left Ventricular Function

■

Radial

Longitudinal

Displacement

Acoustic quantification

Annular
M-mode
Tissue tracking

Thickening

Anatomic M-mode

Velocity

Velocity of displacement
Longitudinal velocity

Tissue Doppler
velocity

Velocity
gradient

Tissue Doppler gradient

Strain

Timing

Tissue Doppler

Tissue Doppler


210

Section VI—Coronary Artery Disease

Table 46.3  Positive and Negative
Aspects of Tissue Doppler with Stress
Echocardiography
Positive

Negative

Feasible

Works in most patients, but
not all

Simple

Concordance limited by
positioning sample volume

Good evidence base

Image quality problem

Supplement to wall motion
scoring rather than
replacement

Automated peak detection
not robust yet
Diagnosis of coronary artery
disease, not ischemia
Apex

of coronary disease, comparable with that attainable by an
expert observer.6 More importantly, an increment of accuracy
can be obtained by use of these techniques by less expert
readers7 and appears to add some prognostic information.8

The alternative strategy is to use a more sophisticated modeling approach developed by a multicenter European group
(MYDISE) (Table 46.3). This more complex approach takes
into account age and stress variables and offers a very high
accuracy,9 although it has not been compared with an expert
interpreter.
The use of peak myocardial velocity has a number of disadvantages (see Table 46.3), and it would be fair to say that
the technology has never caught on for stress echocardiography. Image quality remains an important determinant of
accuracy. The biggest problem is that tissue Doppler measures
velocity relative to the transducer, with ensuing influence by
translation and rotation of the heart, as well as tethering of
adjacent segments. This means that normal tissue may
augment the velocity of ischemic segments and abnormal
tissue may reduce the velocity of normal segments. The evaluation of myocardial deformation may offer a means of avoiding this situation.

Tissue Deformation Approaches
General Observations
In contrast to tissue velocity measurements, which measure
velocity relative to the stationery transducer, strain rate (SR)
approaches are based on the comparison of adjacent velocities
(Fig. 46.3). This means that cardiac movement and tethering
by adjacent segments are unlikely to influence these measurements. Using tissue Doppler approaches, SR is measured by
the change of velocity within a sample volume,10 and this
process of comparing potentially noisy velocity curves to
produce a spatial differential of velocity has intrinsic limitations in relation to signal noise. The strain curve appears
smoother because it is obtained by the temporal integral of
SR, but if this parameter is being measured, it is prudent to
observe the velocity and SR curves, which reflect the quality
of the underlying data.

The major attraction of SR imaging (SRI) is its high site

specificity. A number of clinical and experimental models
have shown that SRI is a sensitive marker of the development
of ischemia. A second major advantage is that strain is relatively homogenous throughout the heart, in contrast to the
spatial gradients of velocity. Like tissue velocity, strain has
been well validated, both experimentally and clinically.11

Optimal Strain Rate Parameter
A number of deformation parameters may be used for identifying ischemia. If the magnitude of deformation is selected,
SR appears to be the optimal parameter. The normal stress
response of SR is a continual increment in response to dose
increments of dobutamine, with a good correlation between
SR and dP/dt.12 Strain shows an early increment, followed by
a decrement as left ventricular volumes fall in response to
vasodilation from higher doses of dobutamine. In ischemic
tissue, the increment of SR is blunted, as is that of strain (Fig.
46.4), although the lesser increment of strain in normal segments compromises the ability to recognize this as impaired.
The high temporal resolution of SRI also has led some
investigators to recommend the use of the technique to identify delay in the onset or offset of contraction, which is an early
marker of ischemia. While there is experimental and some
clinical evidence to support the use of a technique to identify
time to regional relaxation as a marker of ischemia,13 most
investigators find that signal noise is a problem for timing
measurement and that there is a large variation between
observers.
The measurement of postsystolic thickening is a combination of timing and magnitude parameters and is expressed as
the difference between peak strain and end-systolic strain.
During both “supply side” (e.g., angioplasty14) and “demand”
ischemia (e.g., stress echocardiography15), postsystolic shortening demonstrates more dramatic differences than SR or
strain, although both of these were significantly abnormal in
ischemic tissue.

Clinical Application of SRI With
Stress Echocardiography
Deformation parameters have been used for the detection of
ischemia and viability at stress echocardiography, of which the
latter appears the most feasible. Hoffmann et al.16 compared
tissue velocity with SRI, using positron emission tomography
to define viability. Segments with viable myocardium showed
an increment of SR in response to low-dose dobutamine, and
the distinction of viable and nonviable tissue with SRI was
significantly more accurate than with tissue velocity,16 reflecting the limitations of tethering by adjacent statements. A subsequent follow-up study demonstrated that the low-dose
dobutamine response of SR and strain were predictive of
recovery after revascularization, with sensitivities and specificities of various parameters ranging from 74% to 80%.17
Interestingly, these results were comparable to wall motion
analysis by an expert reader, and an increment in accuracy
only arose from the combination of SR and strain with wall
motion analysis in that study.
The application of SRI to the detection of ischemia remains
technically challenging, and the evidence in support of using
SRI remains somewhat limited. A study of 44 patients, 19 of


Section VI—Coronary Artery Disease



211

TISSUE DOPPLER DURING STRESS ECHO
Tissue Doppler to strain rate imaging

TVI

STRAINRATE

[1/s]

[m/s]

BLUE (or
trace above
baseline) ϭ
expansion

V2
V1

GREEN ϭ no
deformation
RED (or trace
below baseline)
ϭ contraction

Ultrasound beams

Ultrasound beams

TVI measures velocities relative to
the transducer

Strain measures velocities relative to

adjacent velocities

Fig. 46.3 The advantages of SR approaches to imaging are illustrated. In contrast to tissue velocity imaging (TVI), which measures velocities relative
to the transducer, strain measures velocities relative to adjacent velocities. Thus with SR approaches, measurements are less likely to be influenced
by cardiac movement and tethering of adjacent segments.

Strain

AS – Inferior wall

SR

Rest

Stress

Fig. 46.4 In this patient with right coronary artery disease, strain and SR imaging of the inferior wall were normal at rest (left panels). However, with
stress echocardiography, deformation imaging confirmed the presence of ischemia involving the basal segment of the inferior wall. In this segment,
strain was <10% and SR was <1s−1.