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3
5
Echocardiographic
Evaluation of Coronary
Artery Disease
Stephanie A. Coulter
Measurement of Regional Myocardial Function . . . . . .
Assessment of Coronary Ischemia/Acute Myocardial
Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Location of Acute Myocardial Infarction . . . . . . . . . . . .
Extent of Acute Myocardial Infarction . . . . . . . . . . . . . .
Acute Complications of Acute Myocardial
Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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813
814
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Chronic Complications After a Myocardial
Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 819
Prognosis in Acute Myocardial Infarction and
Chronic Coronary Artery Disease . . . . . . . . . . . . . . . 821
Stress Echocardiography: Assessment of Ischemic
and Viable Myocardium . . . . . . . . . . . . . . . . . . . . . . . 823
815
C
oronary artery disease (CAD) is the most prevalent of
cardiac diseases. Routine evaluation of patients with
suspected or known CAD nearly always includes
echocardiography. Echocardiography is a versatile, low-cost,
and portable technique that is available clinically in nearly
all medical centers and subsequently is the most widely utilized cardiac testing modality. The diagnosis of CAD by
echocardiography is based on the concept that acute myocardial ischemia or infarction produces a detectable impairment
in regional left ventricular (LV) mechanical function. Identification of patients with suspected CAD and acute coronary
syndrome is one of the primary indications for echocardiography. Assessment of global LV systolic function and detection of the presence and extent of regional myocardial
dysfunction are routine clinical indications for echocardiography. This method also has an important prognostic value
in patients with acute and chronic CAD. When combined
with exercise or pharmacologic stress testing, echocardiography can identify patients with myocardial ischemia and
viability. Because echocardiography can provide a comprehensive assessment of cardiac structure, function and possibly perfusion at the bedside, it is likely to be the technique
of choice for years to come.
Measurement of Regional Myocardial Function
Regional Wall-Motion Abnormalities
Regional systolic and diastolic function can be characterized
by measuring one or more of the following parameters: the
timing of regional events, regional myocardial thickening
and thinning, and the velocity and direction of regional myo-
cardial motion.1 With echocardiography, a regional wallmotion abnormality (RWMA) is characterized as a localized
decrease in the rate and amplitude of endomyocardial motion.
These abnormalities are accompanied by a reduction
in myocardial thickening during systolic contraction and
by thinning of the myocardial segment after a transmural
myocardial infarction (MI). The loss of systolic wall
thickening is more specific for myocardial ischemia than
is the detection of a resting RWMA 2–5 because cardiac
rotation, translational motion during contraction of bordering segments, and loading conditions affect the latter fi nding.
An RWMA is not specific for coronary ischemia and also
occurs with a previous MI, a previous sternotomy, myocarditis, cardiomyopathies, left bundle branch block, and
preexcitation.
The American Association of Echocardiography recommends a 16-segment standardized format for describing
RWMAs.5 To update and unify reporting of wall-motion
analysis among disparate cardiac-imaging modalities, in
2002 the American Heart Association (AHA) issued a statement on myocardial segmentation and nomenclature that
revised the format to include 17 segments (Figs. 35.1 and
35.2).6 In both the 16- and 17-segment formats, the ventricle
is divided into roughly equal thirds perpendicular to the
apical long axis of the heart (basal, midventricular, and apical
on short-axis imaging). The basal segments extend from the
mitral annulus to the tips of the papillary muscles at enddiastole. The midcavitary segments extend the length of the
papillary muscle. The apical view begins just beyond the
papillary muscles and extends to just before the end of
the cavity. The 17th segment encompasses the true apex, or
apical cap, which includes the portion of the apical myocardium not bordered by the ventricular cavity.
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2 Two chamber
3 Long axis
1 Four chamber
Apical cap
Apical cap
Apical cap
Apical
Apical
Apical
Apical
Apical
Apical
lateral
inferior
anterior
lateral
anterior
4
septum
Mid
Mid
Mid
Mid
Mid
Mid
5
inferolateral anteroseptum
anterolateral inferior
anterior
inferoseptum
Basal
6
Basal
Basal
Basal
Basal inferolateral anteroseptum
Basal
inferoseptum
inferior
anterior
anterolateral
3
2
1
Base
Anterior
AnteroAnterolateral
septum
Anterior
Anteroseptum
Inferoseptum
Interior
InferoInferoseptum
lateral
Interior
4
Inferolateral
5 Mid
6 Apex
Anterolateral
Anterior
Septal
Lateral
Interior
FIGURE 35.1. Analysis of wall motion. The left ventricle (LV) can be
divided into 17 segments and identified by a series of longitudinal
views: 1, apical four chamber; 2, apical two chamber; 3, apical long
axis, or a series of short-axis views; 4, base (short axis at the tips of the
mitral leaflets); 5, mid-cavity (short axis at the papillary muscles); and
6, apex (short axis beyond the papillary muscles but before cavity
ends). The longitudinal and short-axis views overlap and complement
each other. The apical cap, the 17th segment, can be appreciated only
by echocardiography with contrast opacification of the LV cavity. A
16-segment model can be used without the apical cap. long axis;
apical four chamber; apical three chamber; apical two chamber.
The wall-motion score index is an expression of regional
LV function that is directly proportional to the severity and
extent of an RWMA. Each myocardial segment is scored on
a scale of 1 to 5, according to a qualitative assessment of
regional function and systolic thickening (normal, 1; hypokinesis, 2; akinesis, negligible thinning, 3; dyskinesis,
paradoxical systolic motion, 4; and aneurysm, diastolic
deformation, 5) (Table 35.1). The composite score, divided by
the number of segments, provides a semiquantitative evaluation of regional wall motion.5,7 Previous authors have rec-
ommended a four-point wall-motion scoring system,8,9 but
the American Society of Echocardiography (ASE) recently
continued to advocate a five-point scoring system, which
included the discrimination of aneurysmal segments.7 The
16-segment format is recommended for evaluating regional
LV dysfunction with two-dimensional (2D) echocardiography, because the 17th apical segment does not exhibit inward
motion.7 Although the coronary artery blood supply to the
myocardial segments varies, the typical relationship between
the three coronary arteries and the myocardial segments is
illustrated in Figure 35.3.
Left ventricular segmentation
1
7
2
8
14 17
9
3
6
13
15
10
12
16
11
5
4
1. basal anterior
7. mid anterior
13. apical anterior
8. mid anteroseptal
2. basal anteroseptal
14. apical septal
9. mid inferoseptal
3. basal inferoseptal
15. apical anferior
4. basal inferior
10. mid inferior
16. apical lateral
17. apex
5. basal inferolateral
11. mid inferolateral
6. basal anterolateral 12. mid anterolateral
FIGURE 35.2. Display, on a circumferential polar plot, of the 17
myocardial segments and the recommended nomenclature for
tomographic imaging of the heart.
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Regional Myocardial Doppler Velocities
Differentiation of passive motion from active myocardial
shortening or thickening is limited by the temporal resolution (about 90 ms) required to detect differences in motion
with the unaided human eye.10 Measurement of the speed of
motion of low-frequency myocardial tissue can be obtained
with pulsed-wave tissue Doppler imaging (TDI), which excludes the high-frequency velocities of the rapidly moving
blood. Assessment of peak regional myocardial velocities
with TDI techniques can be achieved in simultaneous segments at high frame rates. The accuracy of tissue Doppler
imaging is limited by translational motion and tethering
effects.11–16 Clinical limitations of this technique are attributed to the complexity of myofiber orientation, which creates
motion in three dimensions: longitudinal shortening (base >
middle > apex), radial thickening (all segments), and circumferential rotation (apex). Ability to image in only one plane
and misalignment of the Doppler probe with the vector of
cardiac motion diminish the accuracy of Doppler velocity
imaging and may limit its clinical applicability at this time.17
Strain imaging is a method for calculating regional myocardial function from TDI velocity data, which theoretically is
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TABLE 35.1. 1. Wall motion score
Score
Wall motion
Defi nition
1
2
3
4
5
Normal/hyperkinesis
Hypokinesis
Akinesis
Dyskinesis
Aneurysmal
Normal systolic motion and thickening
Reduced systolic motion or thickening
Absent inward systolic motion or thickening
Paradoxic (“bulging”) or outward motion
Diastolic deformation
Each segment should be analyzed and individually scored according to its systolic motion and thickening. Confi rmation should be made with multiple views.
not confounded by translational movement or tethering.17
Strain rates reflect the speed of regional myocardial longitudinal deformation and are calculated from myocardial TDI
velocities measured at two locations separated by a given
distance.7 The longitudinal segmental strain rate is uniform
throughout all segments, whereas TDI is greatest at the base
and deteriorates as the motion becomes more circumferential toward the apex.12,15,18 With ultrasonic strain-rate imaging,
both the amount of deformation (strain) and the rate of local
deformation (strain rate) can be quantified.13
Myocardial Performance Index
The myocardial performance index (MPI) provides a noninvasive, semiquantitative assessment of global LV function,
incorporating systolic and diastolic function. The MPI is the
sum of the diastolic intervals, isovolumic relaxation time,
and isovolumic contraction time, divided by the systolic LV
ejection time. The MPI is reproducible and less dependent on
the heart rate and preload than are traditional Doppler measurements.19,20 In the normal heart isovolumic diastolic times
shorten with increasing contractility.21,22 With ischemia, the
MPI has been shown to deteriorate as the isovolumic relaxation time increases relative to ejection times.23 In patients
with known LV dysfunction after an acute MI who were
enrolled in the Survival and Ventricular Enlargement (SAVE)
trial,24 an MPI of >0.5 was associated with a larger infarct
FIGURE 35.3. Typical distributions of the right coronary
artery (RCA), the left anterior
descending (LAD), and the
circumflex (Cx) coronary
arteries. The arterial distribution varies between patients.
Some segments have variable
coronary perfusion.
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RCA
LAD
RCA or Cx
Cx
RCA or LAD
size and reduced baseline LV systolic function. The MPI was
also identified as an independent predictor for cardiovascular
events after an MI in patients with LV systolic dysfunction.
Because diastolic abnormalities precede the development of
systolic alterations in the ischemic cascade, the MPI may be
more sensitive for the detection of myocardial ischemia. It
has been utilized with dobutamine stress echocardiography
(DSE) for the detection of ischemia after an MI. The MPI
provided added prognostic value to DSE and accurately
reflected the LV contractile state during low-dose DSE.23 The
MPI may reflect the overall LV functional reserve.
Unfortunately, systolic wall motion and thickening is
often difficult to detect and quantify. Doppler techniques
lack clinical applicability, and determining the myocardial
performance index is time-consuming. Therefore, 2D grayscale echocardiographic assessment remains the standard
clinical modality for detecting RWMAs.
Assessment of Coronary Ischemia/Acute
Myocardial Infarction
The echocardiographic evaluation of coronary ischemia and
of regional myocardial dysfunction during an MI varies
widely over a range of coronary blood flows.25 Regional wallmotion abnormalities occur with coronary artery stenosis of
>85% at rest and >50% during exercise or hyperemia.7 They
arise within seconds after a coronary occlusion is induced
1 Four chamber
2 Two chamber
3 Long axis
4 Base
5 Mid
6 Apex
LAD or Cx
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Workload (HRxBP)
Necrosis
MI
Stunning/Hibernation
Global LV dysfunction
Chest pain
ECG changes
Wall motion
abnormalities
Elevation of
Perfusion Metabolic
LVEDP (SOB)
deficits abnormalities
Resting flow reduction
Rest
Exercise time
FIGURE 35.4. Ischemic cascade. Schematic representation of the
clinical, electrocardiographic, and echocardiographic manifestations of myocardial ischemia as the workload (rate-pressure product)
and duration of stress is increased. SOB, shortness of breath.
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1.0
0.8
Event-free survival
by balloon inflation during angioplasty and may last for up
to several days with prolonged ischemia.26,27 These abnormalities precede the development of electrocardiographic
irregularities and the onset of cardiac symptoms. Figure 35.4
illustrates the cascade from myocardial ischemia to infarction. During an episode of acute ischemic chest pain, 2D
imaging should show RMWAs that normalize on resolution
of the ischemia unless the duration of ischemia is sufficiently long to induce myocardial stunning.28 The transient
nature of the RMWA differentiates a brief episode of acute
myocardial ischemia from an acute MI. The presence of an
RWMA does not establish the diagnosis of acute ischemia.
However, the presence of an aneurysm and myocardial thinning suggests a previous ischemic event. For diagnosing
acute coronary ischemia, echocardiography has a high sensitivity but a low specificity.29,30
In a large study,29 1017 patients with suspected cardiac
chest pain without ST-segment elevation were evaluated
with standard clinical and electrocardiographic variables in
the emergency room. The presence of RWMAs was assessed
with 2D echocardiography. The sensitivity of RWMAs for
detecting acute coronary syndrome was 88%, but the specificity was only 18%. Patients with RWMAs were 6.1 times
more likely to experience an early cardiac event than those
without RWMAs. The presence of a RWMA significantly
increased the ability of clinical and electrocardiographic
variables to predict early (within 48 hours) major adverse
cardiac events. In patients with symptoms of an acute coronary syndrome, nondiagnostic electrocardiography, and
normal biochemical markers, demonstration of normal
global systolic function by handheld echocardiography had a
91% negative predictive value for acute MI.31 The addition of
perfusion imaging to routine echocardiographic assessment
of RWMAs and clinical variables in patients with suspected
cardiac chest pain and nondiagnostic electrocardiograms
improved the prediction of cardiac events. The addition of
perfusion imaging in patients with suspected cardiac chest
pain and nondiagnostic electrocardiograms further enhanced
the clinical Thrombolysis in Myocardial Infarction (TIMI)
35
Normal RF,
Normal MP
0.6
Abnormal RF,
Normal MP
0.4
Abnormal RF,
Abnormal MP
0.2
0.0
0
2
4
6
8 10 12 14 16 18 20 22 24
Months of follow-up
FIGURE 35.5. Perfusion imaging enhances the clinical prediction
of future cardiac events in patients with suspected cardiac chest
pain. Event-free survival in patients with an intermediate-risk modified Thrombolysis in Myocardial Infarction (TIMI) score (3 or 4).
MP, myocardial perfusion; RF, regional left ventricular function.
risk score and the ability of RWMAs to predict cardiac events
(Fig. 35.5).32
Because early detection of RWMAs adds significant diagnostic and prognostic value to the routine evaluation of
patients who present to the emergency department with suspected cardiac chest pain, a joint task force of the American
College of Cardiology (ACC), AHA, and ASE in 2003 issued
a class I recommendation for the use of echocardiography in
diagnosing suspected ischemia or infarction when standard
means of diagnosis were inconclusive.33,34
Location of Acute Myocardial Infarction
Two-dimensional and Doppler echocardiography provides
assessment of the location and extent of myocardial damage,
associated and preexisting valvular dysfunction, and ventricular and pulmonary artery pressures. Cardiac enzymes
and the electrocardiogram are crude determinants of infarct
size and location.35 Validation studies with thallium-201
scintigraphy, technetium-99m pyrophosphate (99mTc-PYP)
scintigraphy, serum creatine kinase–MB levels, and coronary
arteriography demonstrate that 2D echocardiography accurately detects and identifies the anatomic location of MIs.36–39
Two-dimensional echocardiography is less precise (sensitivity, 60% to 75%) in detecting nontransmural MIs, presumably because transmural muscle loss is less than 20% and
preservation of the contractility of subepicardial myocardial
layers can mask subendocardial dysfunction.40 With an acute
MI, the uninvolved myocardium shows a compensatory
hyperdynamic contractile response, the absence of which
may indicate multivessel disease.41 The location of RWMAs
correlates with the distribution of the occluded coronary artery, especially if the obstruction involves the left
anterior descending (LAD) or posterior descending coronary
arteries.42
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Left anterior descending artery obstruction creates severe
wall-motion abnormalities (akinesis with complete obstruction) of the septum, anterior wall, and apex. These segments
are best visualized from the parasternal long-axis (anteroseptum), and apical four- (septum and apex) and two-chamber
(anterior wall and apex) views. The location of the obstruction along the vessel length (proximal, middle, or distal)
corresponds to the severity and extent of the resulting
RWMA. The LAD may supply a variable (and often large)
proportion of the LV apex. Occlusion of the LAD may lead
to distal inferior and distal inferolateral wall-motion
abnormalities.
Left circumflex artery (LCx) occlusion typically affects
perfusion of the anterolateral and inferolateral segments.
Imaging in the parasternal long-axis (inferolateral wall) and
the apical four- and apical long-axis views (inferolateral wall)
augment the short-axis exam for visualization of the typical
LCx infarction. In approximately 20% of patients, the LCx
supplies the posterior descending artery (left dominant
system), and interruption of the LCx blood flow can lead to
an extensive RWMA that may also include the inferior
septum and inferior free wall.
Occlusion of the right coronary artery (RCA) results in
an inferior RWMA. With proximal RCA occlusion, infarction of the right ventricle may result (see below). The posterior descending artery, a branch of the RCA (right dominant
system) in 80% of patients, supplies the bulk of coronary
flow to the inferior wall. Right coronary artery occlusion
usually spares the apex. Two-dimensional imaging in the
short-axis, basal, and midventricular views, confirmed by
the apical two-chamber view, best reveals inferior wallmotion abnormalities resulting from RCA occlusion. Careful
attention to right ventricle (RV) size and function are important with acute inferior wall infarction.
Bypass grafts and collateral blood flow will blur these
generalizations. A common post-bypass RWMA pattern includes paradoxic septal motion with marked hypokinesis to
akinesis of the septum and normal motion of the anterior
wall (in the absence of a previous anterior infarct).
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patients following revascularization for MI serial echocardiographic studies in 58% showed complete or partial recovery of function. Most of those who improved had more than
a 5% increase in LVEF.46 Echocardiographic assessment of
the infarct size is limited by this method’s inadequate sensitivity in differentiating old versus new infarctions.43
The 2003 ACC/AHA/ASE task force issued a class I
recommendation for the use of echocardiography to assess
infarct size and ventricular function when the results are
used to guide therapy. It gave a class IIa recommendation
(weight of evidence/opinion is in favor of usefulness/efficacy)
for echocardiographic assessment of ventricular function
after revascularization.33,34
Acute Complications of Acute
Myocardial Infarction
Left Ventricular Failure/Cardiogenic Shock
Cardiogenic shock, a state of inadequate tissue perfusion
related to cardiac dysfunction, complicates approximately
6% to 7% of acute MIs.47–50 Left ventricular pump failure
usually accounts for acute hemodynamic deterioration. In a
small number of patients, however, the cause may be a complication of an acute MI such as rupture of the ventricular
septum, free wall, or papillary muscle with acute severe
mitral regurgitation (MR). A high index of suspicion for one
of these major complications in a patient with hypotension,
tachycardia, a new systolic murmur, or congestive heart
failure is required for rapid diagnosis and appropriate medical
and surgical intervention.51 Two-dimensional echocardiography and pulsed-wave and color-flow Doppler imaging provide
a comprehensive assessment of the anatomic and hemodynamic status at the bedside and therefore are recommended
for patients with hemodynamic deterioration.
Cardiac Rupture
Free-Wall Rupture
Extent of Acute Myocardial Infarction
Cardiac enzymes and electrocardiography are crude indicators of infarct size and location.42 Validation studies with
thallium-201 scintigraphy, pyrophosphate (99mTc-PYP) scintigraphy, serum creatine kinase–MB levels, and coronary
arteriography have shown that 2D echocardiography accurately detects and identifies the anatomic location of
MIs.36,37,43,44 The location of RWMAs correlates with the distribution of the occluded coronary artery, especially if the
obstruction involves the LAD or posterior descending coronary arteries.42
In postinfarct patients, LV systolic function is routinely
measured by the LV ejection fraction (LVEF) on 2D echocardiography. The extent of the infarction can be quantified
with the wall-motion score index. Echocardiography overestimates the infarct size in the presence of a previous infarction and after reperfusion. Reperfusion after an infarct often
leads to early (usually <14 days) improvement in the LVEF as
stunned myocardial segments recover.45,46 In a review of 249
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Rupture of the free wall of the left or right ventricle is found
in less than 1% of living patients with an acute MI,52 but in
as many as 26% autopsied patients who died with an acute
MI.53,54 The most important risk factors for free-wall rupture
are large infarct size53 and delayed hospital admission with
symptoms lasting for >24 hours,55 which are consequences
of inadequate reperfusion. The risk of rupture is further
increased by first MIs associated with poor collateral blood
flow,55 undue in-hospital physical activity,55 age >70 years,
and female sex.56,57 In the National Registry of Myocardial
Infarction database, thrombolytic therapy accelerates the
time course of cardiac rupture (often to within 24 hours) and
increases the risk of rupture-related death (from 7.3% without
thrombolytic treatment to 12.1% with such treatment).52 The
risk of myocardial rupture was significantly decreased
by successful reperfusion with thrombolytic agents in acute
MI patients <75 years of age58–62 or by angioplasty in all age
groups studied.63,64 In a retrospective review of 2209 acute MI
patients treated with percutaneous coronary intervention,64
the risk of cardiac rupture was 0.7% when successful
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reperfusion was achieved within 12 hours, 0.9% when reperfusion occurred within 12 to 24 hours, and 3.8% after failed
reperfusion.
Infarcts of the lateral and anterior LV walls, subtended by
the LCx or LAD coronary artery, are the most common
infarcts associated with free-wall rupture.55 Myocardial
rupture rarely involves the RV or the atria.65,66 The rupture
site is typically located between infarcted and contractile
myocardium.
Myocardial rupture originates as an abrupt slit-like tear,
usually in the anterior myocardium. It occurs early and suddenly, within 3 days following an acute MI in 50% of patients.
In these cases, sudden chest discomfort, with rapidly progressive cardiogenic shock related to hemopericardium and tamponade, are followed by electromechanical dissociation67 and
death. Rapid 2D echocardiography identifies a pericardial
effusion and confirms the diagnosis.68
Contained Free-Wall Rupture:
Ventricular Pseudoaneurysm
Late rupture, more than 5 days after an acute MI, with
infarct expansion, occurs mainly in patients who have had
unsuccessful reperfusion. Late rupture with intramural dissection is more gradual or incomplete and produces the characteristic echocardiographic fi nding of a pseudoaneurysm, or
false aneurysm. An LV pseudoaneurysm results from a localized rupture of the ventricular free wall, which produces a
localized hemopericardium that is limited by parietal pericardium and by blood clot formation. There is an absence of
heart muscle in the wall of a false aneurysm. Although ventricular pseudoaneurysms are usually the consequence of an
acute MI (inferior infarctions being twice as common as
anterior ones), they may also result from cardiac surgery
(most commonly mitral valve replacement), trauma, or laceration.69 A pericardial effusion with organizing thrombus
may help the pericardium seal the ventricular perforation
temporarily, but progression to frank rupture and cardiac
tamponade may occur without warning.70
Echocardiographic recognition of a pseudoaneurysm
associated with a subacute or late LV rupture is difficult.
In a large series of pseudoaneurysms,69 abnormalities were
present on the 2D or Doppler echocardiograms of approximately 85% to 90% of patients, but a defi nitive diagnosis was
made in only about 25%. In suspected cases, coronary angiography provides a defi nitive diagnosis in 87% of patients.69
Transesophageal echocardiography may improve the diagnostic accuracy but has not been studied in this regard. Twodimensional echocardiography can detect discontinuity of
the ventricular free wall and confirm the presence or absence
of pericardial tamponade.71 In most cases, a narrow neck
abruptly connects the LV cavity to the large aneurysmal sac,
which is located outside the LV cavity, is usually pulsatile,
and may contain thrombus. Color-flow Doppler imaging
shows characteristic bidirectional flow in both systole and
diastole, resulting from a communication between the false
aneurysm and the ventricular cavity.
Ventricular Septal Defect
Rupture of the interventricular septum is reported to complicate 1% to 3% of acute ST-elevation MIs.72 Ventricular
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septal defects (VSDs) accounted for 10% of total cardiac
deaths73 before the reperfusion era but only 0.2% of those
observed in the Global Utilization of Streptokinase and
Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I).74 Usually occurring within the first
week, VSDs are more common after large infarctions of the
anterior wall,75 after poorly reperfused infarcts, in the elderly,
and in women.72 Although thrombolytic therapy prevents
septal rupture in many patients who undergo successful
coronary reperfusion, thrombolytic treatment likely accelerates rupture when reperfusion fails. The median time from
the onset of symptoms to the development of an interventricular septal rupture was 1 day in the GUSTO-I trial.74
Septal rupture leads to a sudden left-to-right shunt, whose
magnitude is proportional to the size of the septal defect and
to the ratio of the systemic and peripheral vascular resistance. In this clinical setting, Doppler echocardiography is
usually diagnostic, its sensitivity and specificity reportedly
being as high as 100%.76 Rarely, when the transthoracic
image quality is challenged by mechanical ventilation or
obesity, transesophageal echocardiography is required for
diagnosis. In up to 40% of patients, 2D echocardiography
alone may show a dropout of echoes in the interventricular
septum, in the region of abnormal wall motion (Fig. 35.6A).65
Color-flow Doppler imaging77 has been shown to enhance the
diagnostic accuracy up to 100% by defining the site of septal
rupture as an area of turbulent transseptal flow or by detecting a high-velocity jet on the right side of the ventricular
septum (Fig. 35.6B). Color Doppler examination may show a
single rupture site (typically seen with anteroapical defects)
or multiple rupture sites (characteristically seen with
inferior and inferobasal defects).78,79 Pulsed-wave Doppler
imaging, undertaken on the right side of the interventricular
septum (at the site of the defect), usually characterizes a
high-velocity jet directed from the left ventricle to the right
ventricle (Fig. 35.6C). Right ventricular systolic pressure can
be estimated by subtracting the peak gradient obtained across
the interventricular septum from the systolic (systemic)
blood pressure, provided that no aortic stenosis is present. A
semiquantitative estimate of the size of the left-to-right
shunt can be obtained by measuring the volumetric flow
across the pulmonary valve and the LV outflow tract, provided that no valvular regurgitation is present. Contrast 2D
echocardiography can also identify a VSD. Thus, 2D echocardiography and color-flow Doppler imaging can rapidly and
reliably provide an anatomic diagnosis and estimation of the
hemodynamic status at the bedside. Because the prognosis
depends on early surgical intervention, echocardiography
has become invaluable for the rapid evaluation of this
complication.
Right Ventricular Infarction
Right ventricular infarction, usually caused by proximal
occlusion of the RCA, may complicate up to 40% of inferior
MIs. The echocardiographic manifestations of RV infarction
include RV dilatation, hypokinesis of the RV free wall,80–83
and manifestations of right atrial hypertension48 (dilated
right atrium, plethoric systemic veins) (Fig. 35.7A,B). These
findings are not specific for RV infarction, and they commonly occur with acute and chronic pulmonary hyperten-
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A
817
B
C
FIGURE 35.6. Ventricular septal defect (VSD). (A) Apical VSD
(arrow) is identified by the dropout of interventricular septum visualized by two-dimensional echocardiography. Color Doppler demonstrates an area of turbulence at the site of the VSD rupture in the
apical septum. (B) Color Doppler demonstrates a high-velocity jet of
mosaic color directed into the apex of the right ventricle with migration of blue color toward the base of the right ventricle (RV) (opposite
direction of RV inflow). (C) Spectral Doppler identifies the direction
of the shunt and the magnitude of the pressure gradient from the
left to the right ventricle. The RV systolic pressure can and should
be estimated as the systolic blood pressure (SBP)-4 (peak VSD jet).2
RA, right atrium; LA, left atrium; PK, peak gradient; LV, left ventricle; RV, right ventricle.
sion (pulmonary embolism). An RV infarction almost always
accompanies an infarction of the inferior LV wall (Fig. 35.7C).
Thus, RV dysfunction with akinesis of the inferior LV wall
is characteristic of an RV infarction, having a sensitivity of
more than 80% to 85%.84 Prompt diagnosis of RV infarctions
will differentiate these lesions from other reversible causes
of cardiogenic shock such as cardiac tamponade.
thrombolytic therapy for an acute MI, the Gruppo Italiano
per lo Studio della Sopravvivenza nell’Infarto Miocardio III
(GISSI-3) study85 reported visualization of LV thrombus on
the predischarge echocardiogram of 5.1% of patients (9 ± 5
days after symptom onset). Patients with an anterior MI had
a fivefold higher prevalence of thrombus formation than did
patients with other infarct locations (11.5% vs. 2.3%, respectively). Worsening LV function and more extensive regional
dysfunction are also recognized risk factors for LV thrombus.85 Most thrombi occur within the first 2 weeks (median,
5 to 6 days) after an acute MI.86,87 However, with worsening
LV function, new LV thrombus is identified in some patients
after hospital discharge.87,88
Mural Thrombus
Mural thrombus is a common complication of an acute MI
and had an incidence of up to 40% in patients with anterior
and apical infarctions in the prethrombolytic era. After
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A
35
B
C
FIGURE 35.7. Right ventricular infarction. The manifestations of
right ventricular (RV) infarction can be identified by echocardiography and include RV dilatation (*), hypokinesis of the RV free wall
(arrows), and evidence of elevated right atrial pressure; dilated right
Thrombus, observed at the site of abnormal wall motion
or within an aneurysm, appears as a mobile or an immobile
opaque intracavity mass (Fig. 35.8), which may be laminar or pedunculated or may protrude into the ventricular
cavity.85,89–91 Thrombi are usually located at the apex and, less
frequently, along the septum and the inferior regions of the
heart.92 In detecting LV thrombus, 2D transthoracic echocardiography has a sensitivity of 75% to 95% and a specificity
of 87 to 90%,90,91,93 and therefore is the method of choice.
When the apex is poorly visualized with transthoracic echocardiography, administration of a contrast agent may help
identify suspected apical thrombus by demonstrating an
absence of contrast in an LV cavity filled with contrast. In
transesophageal echocardiography, the posterior position of
the ultrasound probe limits visualization of the apex and
thus detection of apical thrombus. The 2003 ACC/AHA/ASE
task force gave a class I recommendation to the use of
echocardiography for assessing mural thrombus after an
acute MI.33,34
CAR035.indd 818
atrium (RA*) (A), or plethoric inferior vena cava (IVC*, arrow) (B).
Left ventricular inferior wall motion abnormality (arrows) should
also be present (C).
FIGURE 35.8. Left ventricular mural thrombus. Two-dimensional
imaging in the apical four-chamber view demonstrates an echolucency in the LV apex of a patient with a large apical infarct (arrow).
RV, right ventricle; RA, right atrium; LV, left ventricle; LA, left
atrium.
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Embolization has been reported to occur in 26 of 119
patients with documented LV thrombi after an MI.91 Thrombi
that are protruding, pedunculated, or mobile within the ventricular cavity are most likely to embolize, usually within
3 months after an acute MI.91,93–95
Papillary Muscle Rupture Producing Acute
Mitral Regurgitation
Severe MR resulting from papillary muscle rupture is a rare
and often fatal complication of an acute MI.96 In the absence
of prompt surgical intervention, the mortality of this complication is as high as 50% at 24 hours,97,98 which is nearly
double the mortality seen in patients with a postinfarction
VSD.99 The median duration of survival is reportedly 3
days.100 The anterolateral papillary muscle is rarely affected,
because it has a dual blood supply from the LAD and circumflex arteries.101 Infarction of the posterior descending artery
is associated with necrosis of the posteromedial papillary
muscle, which produces sudden clinical and hemodynamic
deterioration and fulminant acute left-sided heart failure. It
is important to recognize that severe MR with complete
rupture of the papillary muscle may occur in the absence of
a cardiac murmur or in the presence of a very soft murmur;
therefore, this diagnosis must be considered with a high
index of suspicion in the appropriate clinical setting. It is
crucial that a defi nitive diagnosis be reached rapidly in these
patients. Two-dimensional echocardiography shows flail
mitral leaflet with attachment of the mobile severed papillary muscle head, which prolapses into the left atrium in
systole, and abnormal cutoff of one papillary muscle (Fig.
35.9A).102,103 In up to 35% of surgically confirmed cases, the
partially ruptured papillary muscle cannot be observed to
prolapse into the left atrium on transthoracic echocardiography imaging.104 Transesophageal echocardiography has
become an invaluable technique for diagnosing acute MR
that complicates an MI, especially in hemodynamically
compromised patients in the intensive care unit, in whom
transthoracic echocardiography imaging may be limited.
Transesophageal echocardiographic imaging in the gastric
A
FIGURE 35.9. Papillary muscle rupture. (A) Transesophageal
imaging in the mid-esophageal four-chamber view demonstrates the
prolapse of the severed head of the papillary muscle (arrow) into the
left atrium (LA) during ventricular systole. The mitral subvalvular
CAR035.indd 819
long-axis and mid-esophageal four-chamber views can detect
the origin of the regurgitant jet and clarify the anatomic
profile of the mitral and submitral valvular apparatus
(Fig. 35.9B).89
Chronic Complications After a
Myocardial Infarction
Ischemic Mitral Regurgitation
Mitral regurgitation caused by changes in ventricular structure and function as a consequence of coronary ischemia is
best described as ischemic MR.105 Usually a consequence of
a previous infarction and chronic LV remodeling, ischemic
MR may also be precipitated by active ischemia, creating
flash pulmonary edema or, rarely, rupture of the papillary
muscle (see above).
Incidence
Ischemic MR occurs in 20% to 25% of patients followed after
an MI106–109 and in 50% of those with congestive heart
failure.110 Moderate or severe MR is found in roughly 40% of
patients within 24 hours of an acute MI complicated by cardiogenic shock.111 However, angiographic detection of moderate-to-severe MR after an MI has been reported in only 3%
to 4% of patients.112,113 When evaluated by echocardiography
within 30 days after an MI, moderate or severe MR was
present in 12%.114 Mild MR has been reported in 50% to 64%
of post-MI patients undergoing echocardiography within 30
days of the MI.106–111,113–115
Mechanism
Mitral regurgitation after an acute MI is due primarily to
segmental and global LV dysfunction, which causes chronic
papillary muscle displacement, apical tethering of the mitral
leaflets, annular dilatation, and decreased systolic mitral
closing forces (Fig. 35.10).105 Elegant models of MR have
shown that ischemia of the papillary muscle in the absence
B
apparatus with rupture of the papillary muscle head (arrow) is
shown by two-dimensional imaging in the deep gastric long-axis
view (B). LV, left ventricle; MV, mitral valve.
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35
Ischemic mitral regurgitation:
incomplete mitral leaflet closure
Normal
Ischemic
LV
closing
force
Papillary
muscle
displacement
Mitral valve
tethering
Tethering
force
LA
Restricted
closure
AO
MR
FIGURE 35.10. Mechanism of ischemic mitral regurgitation. Left:
The balance of forces acting on the mitral leaflets in systole. LA,
left atrium, LV, left ventricle, AO, aorta. Right: Effect of papillary
muscle displacement and mitral leaflet tethering to restrict mitral
leaflet closure. MR, mitral regurgitation.
of infarction does not cause MR.105,116–118 Ischemic MR
depends on a balance of forces and LV geometry and varies
with loading conditions (Fig. 35.11).119 Characteristically
dynamic in nature, MR may be elusive on transesophageal
echocardiography in cardiac surgical patients under anesthesia.120–122 MR is also likely underestimated by resting echocardiography in patients with LV dysfunction and symptoms
of congestive heart failure in the absence of active ischemia.123–125 With semisupine bicycle exercise, Pierard and
Lancellotti125 demonstrated a twofold increase in MR volume
(from mild to moderate-to-severe) and a corresponding
increase in orifice area (by >20 mm2) in nearly 30% of patients.
Exercise-increased MR also correlated with increased
pulmonary artery pressure and conferred an adverse
prognosis.125
A
FIGURE 35.12. Left ventricular aneurysm (LVA). (A) Two-dimensional imaging in the four-chamber apical view demonstrates a thin
distal septum and apical LV segment with a hinge point (arrow)
demarcating the transition from contractile tissue to the aneurys-
CAR035.indd 820
FIGURE 35.11. Illustration of ischemic mitral regurgitation. Twodimensional imaging in the parasternal long axis view demonstrates
apical tethering of the chordae tendineae (left, arrow) and the resultant jet of mitral regurgitation (right) caused by the incomplete
mitral leaflet closure.
Ventricular Aneurysm
After an acute, usually anterior, MI,95,126 a true LV aneurysm
develops in up to 20% of patients, owing to gradual expansion and thinning of all three layers of the infarcted myocardium.127 The incidence of true LV aneurysm has decreased as
reperfusion therapies have improved and become widespread.128 The usual time of aneurysm formation is within 3
months after the onset of an MI. True LV aneurysms almost
always involve the LV apex and extend into the anterior or
anterolateral walls (Fig. 35.12A). Rarely, true aneurysms are
found in the basal inferior or high lateral wall (Fig. 35.12B).
Aneurysms are usually the consequence of left anterior
artery occlusion and are rarely present with multivessel
CAD and extensive collateralization.
B
mal segment. (B) Two-dimensional imaging of the two-chamber
view identifies an aneurysm of the inferior base (arrows) and an
apical thrombus (arrow), which is present in up to one third of
patients with acute myocardial infarction.
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Left Ventricular Remodeling
After an MI, the left ventricle accommodates to the loss of
regional myocardial function by increasing the contractile
state of the remaining viable segments. Left ventricular
remodeling is clinically characterized as a change in cardiac
size, shape, and function as a result of myocardial injury or
an increased load.137,138 The severity of the regional dysfunction (infarct size),139,140 function of the remaining segments,
neurohormonal activation, and presence of coexisting valvular heart disease, particularly MR, will determine the magnitude of LV remodeling.105 This process usually begins
within the first few hours after the infarct and progresses
over time.141–143 Disproportionate thinning and dilatation of
the infarcted segment after an MI is defi ned as infarct expansion and is accompanied by gross distortion of the LV shape
and volume144,145 and loss of functional myocardium that
initially contracted normally.146 With remodeling, the left
ventricle dilates, becomes more spherical, and declines in
function.147 Alterations in LV geometry lead to ischemic MR,
which further increases LV volumes and diastolic wall stress,
activates the neurohumoral cascade, and further decreases
LV contractility, thus leading to a cycle of LV remodeling and
MR.105 The important relationship between LV function and
MR is reflected in the poor survival of post-MI patients in
whom both significant MR and severe LV dysfunction coexist
(Fig. 35.13).111
Echocardiographic assessment of LV remodeling after an
acute MI includes 2D measurements of the LVEF, size, shape,
CAR035.indd 821
1.0
0.9
0.8
Proportion alive
Two-dimensional echocardiography has a sensitivity of
>93%129 and a specificity of 94% in the detection of LV aneurysm. The characteristic echocardiographic fi nding is a
thin LV wall that fails to thicken during systolic contraction, producing a “bulge” during systole and diastole.127,130 A
common finding is a hinge point (Fig. 35.12A), or junction,
between contractile LV tissue and the akinetic, often paradoxic, motion of the aneurysm. True LV aneurysms distort
LV geometry during both systole and diastole.129 Doppler
echocardiography can be used to detect a low-velocity flow
profile with a “swirling” motion characteristic of low cardiac
flow within the aneurysm. Thrombus within the aneurysmal segment is detected echocardiographically in at least a
third of patients with LV aneurysms (Fig. 35.12B),131,132 and
such thrombus may account for the increased risk of stroke
in the 5 years after an acute MI.133 Deposition of fibrous
tissue and calcium in the aneurysmal segment over time
prevents rupture of a chronic LVA, unlike a pseudoaneurysm.134,135 Left ventricular aneurysms contribute to chronic
cardiac decompensation with congestive heart failure, ventricular arrhythmias, and systemic emboli.
Compared to medical therapy alone, surgical repair of LV
aneurysms in selected patients improves survival, functional
class, and symptoms.136 Two-dimensional echocardiography
has been used to evaluate the efficacy of aneurysmectomy in
patients with ventricular aneurysms. Ryan and colleagues126
found that a fractional shortening of >17% in the uninvolved
myocardium (measured at the base of the heart) was associated with an improved surgical outcome, whereas a fractional shortening of ≥17% entailed no subsequent clinical or
surgical improvement.
8 21
0/1 MR, LVEF ≥28%
0.7
0.6
0.5
0.4
2/3/4 MR, LVEF ≥28%
0/1 MR, LVEF <28%
0.3
0.2
0.1
2/3/4 MR, LVEF <28%
0.0
8
10
12
4
6
Time from randomization (months)
FIGURE 35.13. Survival following myocardial infarction is dependent on both left ventricular ejection fraction (LVEF) and the severity of mitral regurgitation (MR). Kaplan-Meier estimates of survival
up to 1 year after randomization for four combinations of LVEF and
MR in the SHOCK trial. Total n = 90; MR 0/1 and LVEF >28%, n =
33; MR 0/1 and LVEF <28%, n = 20; MR 2/3/4 and LVEF >28%, n =
16; MR 2/3/4 and LVEF <28%, n = 21.
0
2
and volume at end-diastole and end-systole and should
also include Doppler estimation and quantification of MR
severity.
Prognosis in Acute Myocardial Infarction and
Chronic Coronary Artery Disease
In patients with CAD, the prognosis is related to the extent
of myocardial damage, the magnitude of the resultant LV
remodeling, the LV fi lling pressures, and the degree of residual coronary ischemia and viability. As a cardiac imaging
modality, echocardiography is uniquely suited for the routine
examination of each of these important predictors of
outcome. Two-dimensional echocardiography can be used to
identify patients with acute MIs who are at high risk for
short-term complications in the hospital and for long-term
complications after hospital discharge.148–151 Horowitz and
Morganroth149 found that echocardiography had a sensitivity
of 83% and a specificity of 85% in identifying patients at
high risk for in-hospital complications.
Ventricular Systolic Function
Left Ventricular Systolic Function
The extent of myocardial damage can be measured globally
as the ejection fraction or regionally as a wall-motion score
index. Both parameters have been shown to correlate with
the outcome in patients with an acute MI or chronic CAD
(Fig. 35.14).28,30,152,153 Nishimura and colleagues150 found that
post MI patients with a higher wall-motion score index at
discharge are more likely to have cardiovascular complications at follow-up examination. The LVEF and severity of MR
were the only independent echocardiographic predictors of
both early and late survival for patients presenting with cardiogenic shock. Survival at 1 year was 24% in those with an
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10
Left Ventricular Remodeling
<30%
Total = 3197
Mortality (%)
8
6
No study
within 14 days
4
30–39%
40–49%
2
≥60%
50–59%
N = 630
0
162
35
355
604
835
611
15
30
45
60
75
Resting ejection fraction (%)
FIGURE 35.14. Left ventricular systolic function predicts mortality
after myocardial infarction. Relation of rest ejection fraction to allcause mortality in 3197 patients enrolled in the TIMI II study.
Kaplan-Meier analysis of mortality rate related to time from study
entry, with patients categorized according to ejection fraction. Mortality rate is highest in patients with ejection fraction <30% (9.9%).
LVEF of <28% versus 56% for those with a higher LVEF.111 In
the setting of acute coronary syndrome, LV systolic dysfunction increases the long-term mortality and increases the
probability of having multivessel CAD by 50%.154
Left ventricular remodeling can be characterized and quantified by 2D echocardiographic measurements of LV size and
volume. The prognosis in patients with CAD is also related
to the extent of LV remodeling. After an acute MI, small
increases in LV volume (particularly LV end-systolic
volume)156,157 or decreases in the LVEF158 increase the risk of
death and congestive heart failure.156,159
In-hospital evaluation of the postinfarct LVEF and the
extent of RWMA, but not LV dilatation, predicted progressive
LV remodeling.143,146 In the Beta-Blocker Evaluation of Survival Trial (BEST), however, Grayburn and colleagues160
found that LV volume and MR were the best predictors of
outcome in patients with LV dysfunction.
Mitral Regurgitation
The presence and severity of ischemic MR has been shown
to worsen survival in patients with acute MI and chronic
CAD with or without LV dysfunction.107,109,111–114,161–163 Mitral
regurgitation that follows an acute MI is an important independent predictor of early and late death.109,113 In the SAVE
trial,24 any degree of MR detected within days after an MI
was associated with a poorer outcome, which was independent of treatment with angiotensin-converting-enzyme
inhibitors (Fig. 35.16A). Survival correlated with the severity
Right Ventricular Systolic Function
In 416 patients with LV dysfunction (LVEF <40%) after an MI,
persistent RV dysfunction has been shown to decrease overall
survival. The RV systolic function correlated weakly with
the LV systolic function. However, RV function, measured
as a fractional area change, was an independent predictor of
mortality, cardiovascular mortality, and congestive heart
failure. Each 5% decrease in RV fractional area change
increased the odds of cardiovascular mortality by 16%
(Fig. 35.15).155
100
No RV Dysfunction n = 337
HR = 3.2 (2.0–5.1) p <.0001
Survival (%)
75
RV Dysfunction n = 79
50
25
0
0
500
1000
1500
Days
FIGURE 35.15. Right ventricular dysfunction following myocardial infarction decreases survival. Cumulative percent survival of
patients with and those without right ventricular (RV) dysfunction
measured as fractional area change (FAC). RV dysfunction = FAC
<32.2%; normal RV function = FAC >32.3%; HR, hazard ratio.
CAR035.indd 822
FIGURE 35.16. (A) Mitral regurgitation (MR) worsens survival after
myocardial infarction. Kaplan-Meier curves of cardiovascular survival in patients with and without MR following acute myocardial
infarction in the Survival and Ventricular Enlargement (SAVE)
Study. MR, mitral regurgitation. (B) Decreased survival after MI
with increasing severity of MR. Degree of MR quantified by effective regurgitant orifice area (EROA); mild if EROA <20 mm2 and
moderate or greater when EROA ≥20 mm2. Numbers at bottom indicate patients at risk each interval.
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1.0
E/e’ ≤15
Survival
0.9
0.8
0.7
0.6
0.5
0
Number at risk 250
A
E/e’ > 15
6
12
18
24
195
113
49
16
Duration of follow-up (months)
1.0
0.9
Em >5 cm/s
0.8
0.7
3< Em ≤5 cm/s
0
Elevated Left Ventricular Filling Pressures
Elevated LV filling pressures in patients with acute MI and
chronic CAD are the consequence of LV dysfunction, MR,
and ventricular loading conditions. As such, they have been
shown to predict the short- and long-term outcome of patients
with CAD. Elevated filling pressures may be characterized
echocardiographically as a shortened deceleration time (DT)
of mitral early inflow velocity (DT <150 ms), an increased
ratio of early (E) to late (A) LV diastolic filling velocities
(mitral inflow E/A >2), and pulmonary venous diastolic flow
predominance. Additionally, the LA volume, when indexed
to body surface area (>28 mL/m2), reflects the severity and
duration of elevated LV filling pressures and is a powerful
Sm >5 cm/s
0.8
0.7
10
20
30
40
Follow time (months)
B
0.9
3< Sm ≤5 cm/s
Sm ≤3 cm/s
Em ≤3 cm/s
of MR quantified as effective regurgitant orifice area (EROA)
and regurgitant volume in the elegant studies by Grigioni
and coworkers115,164 (Fig. 35.16B).
In the echocardiographic substudy of the SHOCK trial
(SHould we emergently revascularize Occluded Coronaries
in cardiogenic shocK?),111 the only independent multivariate
predictors of either 30-day or 1-year mortality in patients
with cardiogenic shock after an acute MI were moderate or
greater MR severity and an LVEF of <28% (Fig. 35.13). For
patients with moderate or severe MR, the 1-year survival rate
was 31% compared to 58% for those with mild or no MR.
This outcome is comparable to the mortality of 52% at 1 year
and 24% at 30 days in 50 patients with moderately severe to
severe (3+ to 4+) MR on routine angiography during an acute
MI (total, 1485 patients).113 In these studies, MR severity was
associated with increasing LV volumes, which underlie and
contribute to the mechanism of MR after an acute MI.
CAR035.indd 823
Cum survival
FIGURE 35.17. Elevated left ventricular
fi lling pressures predict survival after
myocardial infarction. (A) Ratio of early
mitral diastolic velocity to diastolic
annular tissue velocity (E/e’) predicts
survival. Kaplan-Meier plot demonstrates improved survival for patients
with E/e’ ratio of <15. (B,C) Peak LV
annular velocities in both systole and
diastole predict survival after MI.
Cumulative cardiac death by tertiles of
the early mitral annulus diastolic velocity (B) and mitral annulus systolic
velocity (C).
Cum survival
1.0
0
10
20
30
Follow time (months)
40
C
predictor of survival after an acute MI.165 Measurements utilizing TDI have provided incremental prognostic information in patients with CAD or congestive heart failure.166–168
After an acute MI, the ratio of the early diastolic mitral
filling velocity to the early diastolic tissue velocity of the
mitral annulus (E/e’ > 15) (Fig. 35.17A)167 as well as the
maximal peak tissue systolic velocity (Sm) (Fig. 35.17C)166
and peak early diastolic tissue velocity (Em) (Fig. 35.17B)166
when added to other echocardiographic variables, further
predicts survival.
Stress Echocardiography: Assessment of
Ischemic and Viable Myocardium
Stress echocardiography is routinely used to document the
presence of CAD, to identify the location and extent of myocardial ischemia, to risk-stratify patients with known CAD,
and to assess myocardial viability in regions of myocardial
dysfunction.
Basic Principles and Definitions
Ischemia is characterized by hypoperfusion of myocardial
cells and can occur at rest or after stress. Viable myocardial
cells are living cells. Viable myocardium is easily identified
when it contracts normally. The discrimination of dysfunctional, but living, myocardium from necrotic tissue is the
more common and clinically relevant description of viability. Ischemia produces regional myocardial dysfunction
within seconds. Experimental studies have shown that the
duration and severity of an ischemic insult is the major
determinant of both functional and metabolic myocardial
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35
TABLE 35.2. Myocardial segment response to stress
Resting
segment function
Stress
Likelihood of
functional recovering
Exercise
Low dose
Peak dose
Interpretation
Normal
Normal
Abnormal*
↑
↓
↑
↑
↑
↑↑
↓
↓
Abnormal
Abnormal
Abnormal
↓
↑
No change
↓
↑
No change
↓
↑↑
No change
Normal
Ischemic
Ischemic and viable
“Biphasic”
Ischemic, viable
Nonischemic, viable
Nonviable, scar
n/a
n/a
High
Moderate
Low
Low
* Viability assessment requires graded stress with image acquisition at multiple stages. Treadmill echo is not recommended for the assessment of viability.
recovery.169 Severe regional LV dysfunction, leading to depression of LV systolic function in patients with CAD, can result
from myocardial necrosis, postischemic stunning, or myocardial hibernation. “Stunning” refers to contractile dysfunction in viable myocardium as a result of transient
ischemia followed by reperfusion.12 “Hibernating” myocardium refers to myocardial tissue that is persistently hypocontractile secondary to chronic or repetitive low coronary
perfusion.170 Hibernating myocardium has been described as
an adaptation to severe and chronic ischemia that increases
the risk of sudden death even in the absence of infarction.171
Recovery of hibernating myocardium is characteristically
late (two of three segments recovering in >3 months) after
reperfusion.
is dependent on visualization of all myocardial segments
and evaluation of myocardial thickening and regional wall
motion. Myocardial contrast agents, which opacify the LV
cavity and better define endocardial borders, enhance the
detection of RWMAs. Tissue harmonic imaging and digital
image acquisition, which allow comparison of side-by-side
optimized images of representative cardiac cycles with
reduced respiratory interference (particularly at peak stress),
have further improved the discrimination of subtle wallmotion abnormalities at various stress stages. Because accuracy of image interpretation remains subjective, physician
experience is a major determinant of the accuracy of stress
echocardiography.172
Treadmill Stress Echocardiography
Interpretation
A new RWMA provoked by stress indicates cardiac ischemia.
Improved contractility of myocardial segments with abnormal baseline function on inotropic stimulation is characteristic of viable but dysfunctional myocardium. A dysfunctional
segment may show one of four responses: (1) an improvement
in contractility (contractile reserve) that further improves
with maximum stimulation; (2) no improvement (nonviable);
(3) worsening function (ischemic); or (4) improvement with
low-dose inotropic stimulation that becomes dysfunctional
at higher doses of inotropic stimulation.8 This biphasic
response is characteristic of viable segments that become
ischemic at higher levels of stress. Table 35.2 summarizes
the myocardial segment responses to stress.
Exercise protocols generally consist of either treadmill exercise or upright or supine bicycle exercise. Baseline images are
acquired before and after exercise in four standard views:
parasternal long-axis (or apical three-chamber), parasternal
short-axis at the level of the papillary muscles, apical fourchamber, and apical two-chamber. Exercise is performed
according to a standard exercise protocol, and the heart rate,
blood pressure, and electrocardiogram are monitored throughout the test at each stage of exercise (Table 35.4). Only postexercise imaging is available with treadmill exercise. Therefore,
rapid acquisition (within 60 to 90 seconds) of postexercise
TABLE 35.3. Selection of stress echocardiography protocols for
clinical decision making
Methodology
Analysis of stress echocardiograms is predominantly based
on qualitative comparison of regional wall motion at baseline and during stress. Semiquantitative assessment of
RWMAs by determining the wall-motion score index
(described above) is recommended. Newer techniques for
quantitation of regional LV systolic function include TDI and
its derivative, strain-rate imaging. Because regional myocardial dysfunction occurs within seconds of acute transient
ischemia, and because recovery usually occurs within 2 to
3 minutes, imaging can be done after stress if performed
rapidly. Stress echocardiography can be performed using
either exercise or pharmacologic stress, depending on patient
ability, laboratory preference, and the reason for clinical
study (Table 35.3). The accuracy of stress echocardiography
CAR035.indd 824
Stress echo protocol
Clinical indication
Chest pain
Post-MI
Viability
Dyspnea
MR
MS
AS
AI
Pulmonary artery pressure
Preop risk assessment
TME
Bike
Dobutamine
+
+
−
+
+
+
+
±
+
++
++
++
++
++
±
±
+
++
±
Valve disease
−
±
+
+
−
+
AI, aortic insufficiency; AS, aortic stenosis; MI, myocardial infarction; MR,
mitral regurgitation; MS, mitral stenosis; TME, treadmill stress
echocardiography.
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TABLE 35.4. Exercise echocardiography protocols
Baseline images
± Doppler
Exercise imaging
Immediate (<1 min)
postexercise
imaging
Treadmill
✓
✗
✓
Bike
✓
✓
✓
Protocols
images is imperative to prevent resolution of an inducible
RWMA and, thus, a false-negative result. The advantages of
treadmill stress testing include the widespread availability
of treadmill equipment and the independent prognostic information obtained from exercise treadmill testing.
Bicycle Stress Echocardiography
Stationary bicycle exercise, either upright or supine, can also
be used for exercise stress echocardiography. As in treadmill
testing, baseline images are acquired before exercise. Patients
then pedal against progressively increasing resistance; the
blood pressure, heart rate, and electrocardiogram are monitored throughout the test at each stage of exercise. One
advantage of supine bicycle testing is that images can be
acquired during exercise. The disadvantage is that many
patients find bicycling in the supine position awkward and
cumbersome, so they may be unable to achieve optimal
stress levels (Table 35.4). However, the onset of ischemia
appears to occur sooner in the supine position, perhaps
Dobutamine dose (μg/kg/min)
40**
*
30
20
10
5
0
3
6
9
12
Advantages
Limitations
High workload
Widely available
Exercise itself is prognostic:
Duration
ECG
Symptoms
Images during exercise
Imaging only postexercise
Lower workload
Difficult for patient
because of the increased venous return, preload, or blood
pressure associated with supine bicycling.173
Pharmacologic Stress Echocardiography
When a patient is unable to exercise, stress is induced with
pharmacologic agents such as dobutamine, adenosine, or
dipyridamole. Dobutamine, the most commonly used agent,
stimulates β1-, β2-, and α-adrenergic receptors, resulting in
both inotropic and chronotropic stimulation. Because of
dose-dependent differences in affinity for the different receptors, low doses produce a predominantly inotropic response,
and increasing doses augment the chronotropic response.
Images are acquired at baseline and after administration of
graded doses of dobutamine, beginning with 5 to 10 μg/kg/
min and increasing the dose every 3 to 5 minutes until reaching a maximum dose of 40 μg/kg/min, at which 85% of
the maximum age-adjusted (220 − age) heart rate is obtained.
Atropine (0.5 to 2.0 mg) is frequently (in up to 25% of
patients)174 used in conjunction with dobutamine to augment
the heart rate response, especially in beta-blocker recipients,
in whom the heart rate response may be blunted.
Figure 35.18 summarizes the DSE protocol. Neither the
electrocardiogram nor the hemodynamic response to pharmacologic stress testing is diagnostic or prognostic. Hypotension during DSE may be related to (1) decreased systemic
vascular resistance associated with a β2-agonist response; (2)
LV outflow tract (LVOT) obstruction produced by systolic
anterior motion of the mitral valve associated with increasing LVOT velocity and reduction in LV systolic cavity size;
(3) hypovolemia; or (4) severe (usually multivessel) ischemia.
Contraindications to DSE include severe arrhythmia, marked
systemic hypertension, severe aortic stenosis, resting LVOT
obstruction, aortic aneurysms, and unstable coronary syndromes (Table 35.5). Testing is terminated when the patient
has completed the protocol and achieved >85% of the
maximal predicted heart rate (MPHR) or if a new RWMA
Time in minutes
TABLE 35.5. Dobutamine stress echocardiography
2D imaging 2 minutes after dose adjustment
* Atropine 0.5–1 mg as needed to achieve
85% MPHR at peak dobutamine dose
** Hand grip exercise may also be utilized to
increase heart rate at peak dose
FIGURE 35.18. Dobutamine stress echocardiography (DSE) protocol.
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Indications
Contraindications
Patient unable to exercise
Graded stress imaging
Identification of viability
Unstable coronary syndrome
Severe arrhythmia
Severe hypertension
Severe aortic stenosis
Aortic aneurysm or dissection
Resting left ventricular outflow tract
(LVOT) obstruction
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TABLE 35.6. Dobutamine stress echocardiography end points
Completed protocol
Achieved target heart rate >85% of (220—age in years)
Cardiac
Angina
New RWMA ≥2 segments
Arrhythmia
Ventricular tachycardia
Atrial fibrillation with rapid response
Supraventricular tachycardia
LVOT obstruction (>4 m/s)
Abnormal blood pressure
≥230/120
SBP ≤80
Intolerable dobutamine reaction
Anxiety, nausea, headache
35
Stress Echocardiography for Detection of
Myocardial Ischemia
Accuracy of Exercise Stress Echocardiography
develops in two or more segments. Development of a significant arrhythmia, LVOT obstruction of >4 m/s, or significant
hypotension or hypertension should lead to cessation of
the dobutamine infusion and termination of the test
(Table 35.6).
In a review of 1118 patients,175 the primary reason for
terminating DSE was achievement of the target heart rate
(52%), completion of the protocol with the maximum dobutamine dose (23%), or development of angina (13%). In only
3% to 7% of patients was the test terminated for a noncardiac
side effect (nausea, anxiety, headache, tremor, urgency).
Overall, the frequency of such side effects was 26%. The
most frequent side effects were arrhythmias, hypotension,
nausea, and dyspnea, but these led to test termination in only
3% of cases.175 The incidence of supraventricular arrhythmia
during DSE has reportedly been as low as 0.5%176 and as high
as 7%.177 Sustained ventricular tachycardia occurs in up
to 6% of DSE studies177,178; acute MI is rare, occurring in
<0.1%.177,178 Provocation of LVOT or midcavity obstruction
with DSE occurs in up to 35% of patients.179,180 Those who
develop LVOT obstruction but not midcavitary obstruction
may be at risk for future chest pain and syncope.181 Women,
patients with diabetes, and those receiving beta-blockers,
calcium channel blockers, or both, were more likely to have
suboptimal stress.
The accuracy of stress echocardiography for the detection of
CAD has been well studied (Table 35.7). In 16 published
studies including 1972 patients, the sensitivity of exercise
stress echocardiography for the detection of coronary stenoses >50% ranged from 71% to 97%.172,182–191 In a literature
review, 44 articles met the criteria for determining the sensitivity and specificity of exercise echocardiography and
exercise myocardial perfusion imaging with single photon
emission computed tomography (SPECT) compared to coronary angiography for the diagnosis of CAD.192 In pooled data,
the two modalities had similar sensitivities for detecting
CAD (85% vs. 87%), but exercise echocardiography had significantly greater specificity (77% vs. 64%). Both tests performed better than standard exercise testing, for which a
sensitivity of 68% and a specificity of 77% have been
reported.193 The sensitivity of exercise echocardiography was
better for the detection of multivessel disease than singlevessel disease (average 92%, range 80% to 100%; vs. average
79%, range 59% to 94%) in nine studies involving 1355
patients.182–185,187,188,190,194 Patient characteristics also influence
the accuracy of exercise stress testing. Left ventricular
hypertrophy, cardiomyopathy, microvascular disease, and
an acute hypertensive response to exercise diminish the
accuracy of exercise echocardiography compared with the
angiographic standard.8 However, stress echocardiography
may be more accurate than exercise myocardial perfusion
imaging in this setting.194–196 Exercise myocardial perfusion
imaging is more accurate in the presence of preexisting
abnormal wall motion, left bundle-branch block, ventricular
pacing, a previous MI, and cardiomyopathy. The accuracy of
exercise echocardiography depends on the exercise level.
Failure to achieve 85% of the MPHR precludes the exclusion
of CAD. Submaximal exercise, single-vessel disease, and
moderate coronary stenosis (50% to 70%) lead to false-negative exercise echocardiographic results. The situations listed
in Table 35.3 are appropriate indications for stress echocardiography. This method is portable, low-cost, and free of
TABLE 35.7. Selected studies outlining the accuracy of exercise echocardiography
Reference
Armstrong et al.182
Crouse et al.183
Marwick et al.184
Quinones et al.185
Hecht et al.186
Beleslin et al.188
Roger et al.187
Marwick et al.189
Marwick et al.194
Luotolahti et al.190
Roger et al.191
Total No.
of patients
Sensitivity (%)
Sensitivity
for 1-VD (%)
Sensitivity
for MVD (%)
Specificity (%)
PPV (%)
NPV (%)
Overall
accuracy (%)
123
228
150
112
180
136
127
161
147
118
340
88
97
84
74
93
88
88
80
71
94
78
81
92
79
59
84
88
—
75
63
94
—
93
100
96
89
100
91
—
85
80
93
—
86
64
86
88
86
82
72
81
91
70
41
97
90
95
96
95
97
93
71
85
97
79
61
87
63
51
79
50
60
91
81
50
40
88
89
85
78
91
88
—
81
82
92
69
1-VD, single vessel disease; MVD, multivessel disease; NPV, negative predictive value; PPV, positive predictive value.
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ionizing radiation. It provides additional information regarding valvular, structural, and hemodynamic factors that affect
patient management and outcome. In a review of 1223 stress
echocardiograms, a significant Doppler abnormality was
detected in 17% (moderate or greater MR, 5.5%; mild or
greater aortic insufficiency, 13%).197 For patients able to
exercise, the 2003 ACC/AHA task force on chronic stable
angina gave a class I recommendation for the use of exercise
echocardiography as an initial diagnostic test or riskstratification technique in patients with known or suspected CAD.34
The accuracy of stress echocardiography in identifying
stenosis has consistently been greater in the LAD territory
than in the RCA and LCx. The reported average sensitivity
of exercise echocardiography for detecting coronary stenosis
is 77% in the LAD, 75% in the RCA, and 49% in the circumflex artery.182,184,198,199 This may be related to the greater extent
of the LAD circulation and the ease with which it may be
imaged. Overlap of the RCA and LCx territories further
limits discrimination between the two.
Prognosis After Exercise
Stress Echocardiography
Electrocardiographic and echocardiographic variables contribute to the prognostic value of exercise echocardiography.
The exercise variables, exercise duration, and ischemic STsegment depression remain important independent
predictors of outcome when modeled with ventricular
function at peak exercise.189 The extent and severity of
exercise-induced LV dysfunction is the most important
prognostic echocardiographic variable associated with ischemia.200–202 Patients with negative stress echocardiograms
have low rates of cardiac events at 1 (1%) and 3 (3%) years of
follow-up. Conversely, patients with abnormal stress echocardiograms (LVEF <50%; wall-motion score index >1.4) had
significant adverse events.203 The negative predictive value
of a normal exercise echocardiogram in patients with normal
exercise tolerance is >99%.201,203–205 The ACC has reported
that stress echocardiography is a useful adjunct to standard
exercise testing and provides a more sensitive and specific
means of detecting myocardial ischemia; the diagnostic
accuracy is similar to that of nuclear technologies, but stress
echocardiography can be performed at a considerably lower
cost.
Accuracy of Dobutamine
Stress Echocardiography
The accuracy of DSE depends on the degree of coronary stenosis and the extent of myocardial ischemia.206,207 Harmonic
imaging and LV opacification with intravenous contrast
agents improve endocardial definition and the accuracy of
DSE.208,209 In a study of 283 patients with suspected CAD, the
positive predictive value of DSE increased significantly as the
extent and severity of induced wall-motion abnormality
increased (more myocardium at risk). Furthermore, the sensitivity increased as a faster maximal heart rate was achieved
(sensitivity: 67% with an MPHR of <75%, 71% with an MPHR
of 75% to 85%, and 86% with an MPHR of >85%; p <.05).207
The sensitivity and specificity for detecting CAD with DSE
mirror those of exercise echocardiography in multiple studies
with a range of sensitivity reported from 70% to 96% and
specificity range from 66% to 93% (Table 35.8).193,195,210–219
A review of 28 studies involving 2246 patients who
underwent both DSE and coronary angiography reported that
DSE had an overall sensitivity of 80%, a specificity of 84%,
and an accuracy of 81%. Like exercise echocardiography, DSE
was more accurate in detecting multiple-vessel than singlevessel CAD (Table 35.8).210 In a review of 120 studies involving 10,817 patients, DSE was more specific than SPECT
myocardial perfusion imaging for the detection of obstructive coronary disease (Table 35.9).212
Prognosis with Dobutamine
Stress Echocardiography
Dobutamine stress echocardiography predicts the prognosis
in patients with CAD. Development of a new or worsening
wall-motion abnormality (ischemic response) occurred in
321 patients, and a fi xed wall-motion abnormality was identified in 237 of 860 patients referred for DSE either for diagnosis of suspected CAD (55%) or for risk stratification in
patients with known CAD (45%).220 Adverse cardiac events
(cardiac death and MI) occurred equally in both groups (14%
and 13%, respectively) within 52 months of follow-up. The
percentage of abnormal segments at peak stress, which incorporates the extent of myocardial dysfunction and the amount
of jeopardized myocardium, predicted a higher risk of subsequent cardiac events (Fig. 35.19). Left ventricular dilatation
at peak stress and a low ischemic threshold also increase
TABLE 35.8. Selected studies outlining the accuracy of dobutamine echocardiography
Author (Ref.)
217
Segar et al.
Marcovitz et al.213
McNeill et al.214
Marwick et al.195
Previtali et al.216
Takeuchi et al.218
Dobutamine
dose range
(mg/kg/min)
Total No.
of patients
Sensitivity
(%)
Sensitivity
for 1-VD (%)
Sensitivity
for MVD (%)
Specificity
(%)
PPV (%)
NPV (%)
Accuracy (%)
5–30
5–30
10–40
5–30
5–30
5–30
88
141
80
217
80
120
95
96
70
72
79
85
—
95
—
66
63
73
—
98
—
77
91
97
82
66
88
83
83
93
94
91
89
89
92
95
86
84
67
61
61
88
92
89
78
76
80
88
1-VD, single vessel disease; MVD, multivessel disease; NPV, negative predictive value; PPV, positive predictive value.
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35
TABLE 35.9. Weighted mean sensitivities, specificities of pharmacologic studies
Pharmacologic test
Adenosine echocardiography
Adenosine SPECT
Dipyridamole echocardiography
Dipyridamole SPECT
Dobutamine echocardiography*
Dobutamine SPECT
Total
Studies
Subjects
Mean age (years)
CAD (%)
MI (%)
Men (%)
Sensitivity (%)
Specificity (%)
6
9
20
21
40
14
516
1,207
1,835
1,464
4,097
1,066
65
63
56
60
59
58
73
80
67
71
70
66
31
17
15
31
26
9
71
59
72
77
66
63
72 (62–79)
90 (89–92)
70 (66–74)
89 (84–93)
80 (77–83)
82 (77–87)
91 (88–93)
75 (70–79)
93 (90–95)
65 (54–74)
84 (80–86)
75 (70–79)
120†
10,817†
CAD, coronary artery disease; MI, myocardial infarction; SPECT, single photon emission computed tomography.
* One dobutamine echocardiographic study not included here because only multivessel disease was examined.
† Total number of tests and subjects exceeds the number of studies reviewed because some studies examined more than one pharmacologic test.
adverse cardiac events.220 Conversely, patients with normal
DSE results have low annual cardiovascular event rates. In a
report of 1737 patients with known or suspected coronary
heart disease (CHD),221 the annual event rate (cardiac death
or MI) at 5-year follow-up was 1.2% when the study was
normal. In a study of 301 patients unable to exercise, both
DSE and dobutamine SPECT myocardial perfusion imaging
were performed and outcomes were determined after 7 years
of follow-up. The predictive value of both methods was equivalent. The annual cardiac mortality was 0.6% and 0.7%, and
the annual cardiac event rates (death, MI, revascularization)
were 3.3% and 3.6%, respectively, when the test was normal.
With an abnormal test, the annual cardiac mortality was
2.8% and 2.6%, and the annual cardiac event rates were 6.9%
and 6.5%, respectively.222
Risk Stratification After a Myocardial Infarction
Dobutamine stress echocardiography has been successfully
used for risk stratification of patients after an acute MI.223–225
In this setting, identification of viable and ischemic segments with DSE improves risk stratification beyond traditional clinical variables.226 In 123 patients with a previous
MI, the diagnostic accuracy of exercise echocardiography for
detecting significant coronary stenoses in infarct-related
arteries was determined by comparison to quantitative coronary angiography performed within 2 weeks of stress echocardiography.227 Treadmill exercise echocardiography was
Event-free
probability, %
100
80
60
40
Normal
Ischemia
Infarction
20
0
% of segments
abnormal at peak stress
≤25
26–50
51–100
0
10
20
30
40
20
30
40
Time, months
Time, months
No. at risk 860 774 641 235 40 860 774 641 235 40
FIGURE 35.19. Abnormalities on dobutamine stress echocardiography predict future adverse cardiac events. Left: Ischemia and fi xed
wall motion abnormalities (infarction) by dobutamine stress echocardiography decrease cumulative cardiac event–free probability.
Right: The percentage of abnormal segments at peak stress increases
the risk of future cardiac events.
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highly sensitive (91%) regardless of infarct size but was less
specific (59%) for detection of infarct-related coronary
lesions.227
Assessment of Myocardial Viability
Viable myocardium has been reported in up to 60% of dysfunctional myocardial segments in ischemic cardiomyopathy.228,229 Myocardial segments that are viable and poorly
perfused should recover function after coronary revascularization. Careful selection of patients for revascularization is
imperative, as the operative mortality for coronary artery
bypass in patients with LV systolic dysfunction varies from
5% to 30% (increasing with age and worsening LV function).230 Furthermore, when performed in patients with
significant global LV dysfunction but little viable myocardium, coronary bypass does not improve global systolic
function.231,232
Dobutamine Stress Echocardiography in the
Identification of Myocardial Viability
Dobutamine stress echocardiography is the preferred echocardiographic method for the assessment of myocardial viability because inotropic stimulation is graded and imaging
can be performed frequently. The DSE protocol for viability
assessment differs from that used for the assessment of myocardial ischemia by including more images at lower dobutamine doses (Table 35.10). The goal is to identify any
improvement in contractile reserve in patients with myocardial dysfunction, which may be transient in those with concomitant ischemia. Viable segments should demonstrate
contractile reserve with inotropic stimulation, normal myocardial thickness, and evidence of some coronary perfusion
and metabolism.233 The biphasic response—initial improvement in contractility followed by deterioration at higher
doses—indicates viable and ischemic myocardium and is a
10
TABLE 35.10. Dobutamine stress protocol
Ischemia
Rest
Pre-peak
vs.
10 μg
Peak > 88%
MPHR
Viability
Rest
10 mcg
5 μg
Peak > 88%
MPHR
MPHR, maximal predicted heart rate.
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100
80
60
%
40
20
0
DE
TI-RR
TI-RI
MIBI
FDG
32
Studies (no.)
22
11
20
20
Patients (no.) 1090
557
301
488
598
Sensitivity
p
Specificity
p
FDG vs others
<.05
DE vs others
<.05
TI-RI vs DE, MIBI <.05
others vs TI-RI <.05
TI-RR vs DE
<.05
MIBI vs TI-RR <.05
FIGURE 35.20. Techniques for the noninvasive assessment of myocardial viability; comparison of weighted sensitivities and specificities. Regional recovery of function after revascularization was the
gold standard for viability. Open bars, sensitivity; solid bars, specificity. DE, dobutamine echo; FDG, fluorine-18 fluorodeoxyglucose;
MIBI, technetium-99m sestamibi; Tl-RI, thallium-201 reinjection;
Tl-RR, thallium-201 rest-redistribution.
ization compared with medical therapy when viability was
present, but there was no benefit when viability was absent
(7.7% vs. 6.2%) (Fig. 35.21).246 Viability testing also predicts
improvement in regional and global LV function after revascularization.246 However, the extent of viable myocardium
required in order to expect improvement in the LVEF after
revascularization may range from 25% to 30% of the left
ventricle.247 Survival is lowest for patients with severe LV
dysfunction and no evidence of viability (mortality, 20% at
18 months), which is independent of revascularization.234
New Echocardiographic Quantitative Parameters
Abnormalities of radial wall thickening are visualized
subjectively by traditional 2D echocardiography as new or
induced RWMAs. Abnormalities of longitudinal deformation can be identified and quantified by TDI and can be
assessed by tissue velocity and displacement, strain and
strain rate imaging, and postsystolic shortening. Tissue
Doppler imaging parameters have been shown to improve
the accuracy of stress echocardiography in detecting myocardial ischemia and viability.
Strain-Rate Imaging
reliable predictor of functional recovery (Table 35.2). The
value of DSE in the identification of myocardial viability
and, therefore, in the selection of patients who may benefit
from revascularization is well established. In a number of
studies in which postrevascularization echocardiography has
been used to assess LV functional recovery after catheterbased or surgical revascularization, the average sensitivity of
DSE to predict functional recovery ranges from 74% to 88%,
and the specificity is 73% to 87%.235–242 The positive predictive value is 81%, and negative predictive value is 87%. Comparative studies have shown a higher specificity and a lower
sensitivity with DSE than with radionuclide techniques
for the identification of functional recovery after the revascularization of dysfunctional myocardial segments (Fig.
35.20).242–244
The end-diastolic myocardial wall thickness obtained by
routine echocardiography is a simple and valuable marker of
viability.245 In a study of 45 patients with stable CAD and
ventricular dysfunction, a myocardial thickness of ≤6 mm
predicted poor recovery of function after revascularization.
Apical segments were the most difficult to measure and
accounted for nearly all of the immeasurable but dysfunctional segments (17%). A myocardial thickness of >6 mm had
a sensitivity of 94% and a specificity of 48% for recovery of
function. A combination of preserved wall thickness and
evidence of contractile reserve during DSE improved the
specificity of DSE to 77% and, thus, is a valuable adjunct to
DSE in the assessment of myocardial viability.
Prognosis: Viability and Potential Benefits
of Revascularization
Patients with viability and LV dysfunction have improved
survival with revascularization compared to medical therapy.
A meta-analysis of 24 nonrandomized studies involving 3088
patients (mean LVEF 32% ± 8%) revealed an 80% relative
reduction in death (3.2% vs. 16%; p <.0001) with revascular-
CAR035.indd 829
Strain-rate imaging provides objective quantification of segmental myocardial function by measuring myocardial deformation or the change in regional myocardial thickening and
is relatively unaffected by adjacent tissue tethering or overall
motion of the heart.248–250 Strain-rate imaging can enhance
echocardiographic detection of ischemia and can differentiate viable from infarcted myocardium.12,15,18,251,252
Ischemia produces a delayed onset and termination of
systolic shortening that is detectable with longitudinal strain
and strain-rate imaging but not by 2D imaging. Evaluation
of regional LV function by TDI velocities, using color Mmode analysis of segmental strain and strain rate, was performed in 44 patients undergoing traditional DSE.16 Ischemia
was defined by concurrent pharmacologic SPECT myocardial perfusion imaging and stenosis confirmed by coronary
–79.6%
χ2 = 147
p<.0001
20
16.0
Death rate (%/yr)
234
15
23.0%
χ2 = 1.43
p = .23
10
7.7
6.2
5
3.2
0
Viable
Nonviable
FIGURE 35.21. Survival following revascularization is increased in
patients with evidence of myocardial viability. Without myocardial
viability, there was no significant difference in survival between
patients treated medically and those revascularized. Open bars,
revascularization; solid bars, medical therapy.
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angiography. Qualitative assessment of strain and strain-rate
curves was possible in 85% of segments. In normally perfused segments, the peak systolic strain rate increased with
increasing dobutamine stimulation. Ischemic myocardial
segments had significantly lower strain-rate increases and
strain than did nonischemic segments. Compared with traditional DSE parameters, strain-rate imaging improved the
sensitivity of DSE from 81% to 86% and the specificity from
82% to 90% (Fig. 35.22).16
With ischemia, the myocardium continues to thicken
during the isovolumic relaxation period.251 This postsystolic
shortening is a sensitive but nonspecific marker of ischemia
that was found in 100% of ischemic segments but also in
47% of nonischemic segments in the study by Voight and
coworkers.16 Postsystolic shortening is not easily identified
by 2D imaging because of its relatively low amplitude and
short duration.10 Strain-rate imaging allows quantification of
postsystolic shortening, which is defined as the maximum
change in segment length occurring between aortic valve
closure and the regional onset of myocardial lengthening
caused by early diastolic LV filling. In one study, the ratio of
postsystolic shortening to maximal segment deformation
was the best quantitative parameter for identifying stressinduced ischemia with DSE.16
Peak myocardial deformation detected by strain-rate
imaging can differentiate active myocardial motion from
passive or translational cardiac motion in both animals and
humans with nontransmural (viable) and transmural infarcted
(scarred) myocardium. This method also allows noninvasive
determination of the extent of nonviable infarcted myocardium.252,253 Myocardial viability assessment with DSE was
improved by the addition of strain-rate imaging in 55 patients
with MIs followed by percutaneous or surgical revascularization.254 The inclusion of regional strain-rate imaging with
routine visual wall-motion scoring identified patients with
significant myocardial viability (an improvement in more
100
sensitivity
[%]
89
80
81
82
specificity
86
60
40
20
0
2D-gray
SRI
FIGURE 35.22. Strain-rate imaging (SRI-CMM) improves the sensitivity and specificity of conventional two-dimensional imaging
(2D-gray) during dobutamine stress echocardiography (DSE).
CAR035.indd 830
35
than four myocardial segments or an overall increase of >5%
in the LVEF after revascularization) and increased the sensitivity of DSE from 73% to 83% without changing the specificity. In a separate study,255 tissue Doppler echocardiography
with strain-rate imaging without DSE differentiated transmural from nontransmural MIs in 47 consecutive patients
with a first acute MI compared to 60 age-matched healthy
volunteers. The peak systolic strain rate (>−0.59 s−1) had a
high sensitivity (90.9%) and specificity (96.4%) in identifying
transmural infarctions. A peak strain rate between −0.98 s−1
and −1.26 s−1 had a sensitivity of 81.3% and a specificity of
83.3% in distinguishing subendocardial infarctions. The
peak strain rate was significantly lower in segments with
transmural infarctions identified with contrast magnetic
resonance imaging compared to normal myocardium or segments with a nontransmural infarction (both p <.0005).255
Perfusion Imaging
Myocardial contrast echocardiography (MCE) is an evolving
technique for the evaluation of myocardial perfusion. Intravenous injection of gas-filled microbubbles scatters ultrasound
and can be used to define LV endocardial borders and myocardial blood flow. Steady-state microbubbles within the myocardium can be destroyed with high-energy ultrasound pulses,
and the rate of microbubble reappearance approximates myocardial blood flow. Improvements in bubble size (<10 μm to
allow transcapillary migration), as well as echocardiographic imaging techniques to enhance detection (harmonic
imaging)256 and enhance the durability of the microbubbles
(triggered imaging)257 with a low mechanical index258 have
greatly improved the potential clinical applicability of this
technique.259,260 Compared to other modalities of coronary
perfusion, MCE has shown progressive improvements in accuracy. Specificities range from 78% to 95%, but sensitivities for
the detection of moderate to severe perfusion defects have
been low (14% to 65%).261,262 A higher number of falsely abnormal results in the circumflex territory have been reported.263
Myocardial contrast echocardiography has been shown to
be accurate in detecting flow-limiting CAD in patients with
suspected CAD and in those undergoing vasodilator stress
testing after an acute MI.264–266 This method may enhance
the predictive value of standard, exercise, and dobutamine
echocardiography. The addition of perfusion imaging has
been shown to improve the sensitivity of routine echocardiography for diagnosing myocardial ischemia in patients
with suspected cardiac chest discomfort and nondiagnostic
electrocardiographic abnormalities.256 The combination of
perfusion defects and wall-motion abnormalities with exercise improved the sensitivity, specificity, and accuracy to
86%, 88%, and 86%, respectively, for establishing the presence of CAD on angiography.267
Abnormal myocardial perfusion imaging during vasodilator stress (dobutamine) echocardiography in 788 patients
contributed significantly to the predictive value of clinical
risk factors, resting systolic LV function, and RWMAs. Eventfree survival at 3 years decreased from 95% with normal wall
motion and normal perfusion to 82% when perfusion was
abnormal and 68% when both wall motion and perfusion
were abnormal. Multivessel perfusion defects predicted the
worst outcomes.268
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FIGURE 35.23. Perfusion imaging with myocardial contrast echocardiography demonstrates myocardial blood flow in viable myocardial segments and may be useful to discriminate coronary arterial
obstruction as a cause of congestive heart failure. Apical four–
chamber view at rest (left) in a patient with acute congestive heart
failure and LV dysfunction (LVEF, 42%) demonstrating normal myocardial perfusion at rest (5 seconds after myocardial contrast
destruction). Right: After dipyridamole stress, four-chamber view
displayed 3 seconds after myocardial contrast destruction. Note
perfusion defect in the septum, apex, and lateral wall. LAD and LCx
flow limiting stenoses were confi rmed by coronary angiography.
Perfusion imaging may help differentiate CAD from
other etiologies in patients with congestive heart failure and
severe LV dysfunction. In 55 patients with acute congestive
heart failure, identification of CAD as the etiology was facilitated by MCE at rest and after dipyridamole stress. Compared to patients without CAD and to normal control
subjects, patients with CAD had a reduced myocardial blood
flow velocity reserve in vascular territories supplied by
vessels with >50% obstruction. In this population, MCE was
the only independent predictor of CAD among clinical, electrocardiographic, biochemical, and resting echocardiographic
variables (Fig. 35.23).269 Myocardial contrast echocardiography may provide an added benefit to dobutamine echocardiography in the evaluation of myocardial viability. The
demonstration of specific patterns of contrast within dysfunctional myocardial segments may discriminate viable
from nonviable myocardium.270
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