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but the end-systolic elastance normalized by end-diastolic volume remained
unchanged. However, it was unclear whether there was a true decline in contractil-
ity or whether the decline in end-systolic elastance was purely a function of the
increased preload. In another study by Starling et al. [15], only the volume axis
intercepts showed a linear relationship with left ventricular end-diastolic volume,
and end-systolic elastance was negatively correlated with left ventricular mass.
Assessment of ESPVR Using Echocardiographic Automated Border Detection
Echocardiographic automated border detection is a new ultrasound technique that
provides real-time online endocardial border detection and is commercially avail-
able as the Acoustic Quantification software package (AQ, Hewlett-Packard/
Agilent Technologies, Andover, Massachusetts). The technique works by differenti-
ating the acoustic backscatter characteristics of bloodfrom myocardial tissue within
an operator-determined region of interest. It then computes an automated border
between blood and myocardial tissue.
The area bound by the automated border is then computed and displayed in the
form of a real-time waveform and values. The area is then extrapolated to estimate
the 3-D volume of the chamber according to the modified Simpson’s method [28].
This technique of computing ventricular volumes and function has been exten-
sively validated against other standard techniques including conventional
echocardiography [29], radionuclide [30] and contrast ventriculography [31], com-
puted tomography [32], MRI [33], and electromagnetic flow meters [34].
Transesophageal echocardiography provides better endocardial border defini-
tion than transthoracic echocardiography because of the higher frequency transduc-
ers and the closer proximity of the transducers to the heart. Therefore, signals
obtained with automated border detection from the transesophageal window are
usually of a superior quality. Logically, automated border detection has been used
with transesophageal echocardiography to quantitate ventricular dimensions [29].
A major drawback with the transesophageal window in extrapolating ventricular
volumes is that the four-chamber view obtained is often foreshortened, resulting in
erroneous calculations.
Transesophageal echocardiographic imaging of the left ventricle at the
midventricular short-axis plane is oftenusedtomonitorventricularvolumeand
function in the intraoperative settings. However, there is no validated formula to
extrapolate the cross-sectional area into ventricular volumes. Gorcsan et al. [34]
have shown a close linear relationship between changes in the cross-sectional area
and changes in stroke volume measured with an aortic electromagnetic flow
probe. Therefore, the cross-sectional area change of the left ventricle as imaged
from the transgastric view can be used as a surrogate for changes in ventricular
volumes.
Volume or area data from automated border detection has been combined with
simultaneous left ventricular pressures to enable construction of real-time left ven-
tricular pressure and volume loops, thus enabling assessment of ESPVR. In a canine
model, Gorcsan et al. [34] combined area data obtained from echocardiographic
automated border detection from the transgastric left ventricular short-axis view
and pressure data from a high-fidelity left ventricular pressure catheter to construct
254 Echocardiography: A Tool for LVSD Identification
pressure-area loops with preload modified by inferior vena caval occlusion cathe-
ters. These pressure-area loops compared favorably with simultaneous pressure-
volume loops with volume data obtained with an electromagnetic flow probe
placed in the ascending aorta.
Changes in stroke area with automated border detection correlated highly with
changes in stroke volume over a wide range of loading conditions. The end-systolic
pressure-area relationships changed appropriately with dobutamine and
propranolol infusions. The authors used the term stroke force to represent the area
bound by the pressure-area curve to distinguish it from stroke work, which is
obtained from volume data. Similarly, the symbol E’ was used for elastance instead
of the usual symbol E.
In another canine model, Gorcsan et al. [35] compared pressure-volume rela-
tionships obtained from automated border detection with those from conductance
catheter techniques. They found that the relative changes in echocardiographic vol-
ume were linearly related to conductance volume at steady state with changes in
end-diastolic volume, end-systolic volume, and stroke work with caval occlusion
also significantly correlated. Although there was an overall bias for absolute
echocardiographic volume to be less and end-systolic and maximal elastance values
to be higher, the direction and relative magnitude of changes in elastance with
inotropic modulation were similar.
10.2.3.2 Stroke Work
The area bound by the left ventricular pressure-volume loop represents the left ven-
tricular external work (Figure 10.3). It is a measure of the total chamber function
and can be considered a measure of contractility as shown in Figure 10.5. However,
it is only applicable as a measure of contractility when the left ventricle is relatively
homogeneous and is of limited use in coronary artery disease with regional wall
motion abnormalities. Left ventricular stroke work is increased in states of chronic
volume overload such as mitral or aortic regurgitation. Attempts have been made to
normalize stroke work to left ventricular volume: This relationship between left
ventricular stroke work and end-diastolic volume is termed preload recruitable
stroke work (PRSW).
10.2 Assessment of Left Ventricular Function—An Overview 255
0
0
100
100
200
200
Loss of
inotropy
Control
loop
Figure 10.5 Loss of inotropy.
10.2.3.3 Preload Recruitable Stroke Work
The PRSW to left ventricular end-diastolic volume relationship is highly linear and
is considered a reliable index of contractility [36]. The slope of such a relationship
(M
SW
) is dependent on ventricular contractility but independent of heart size and
shape. Furthermore, this relationship is sensitive to changes in contractility but not
to changes in loading conditions [36]. The preload recruitable stroke work
relationship can be represented by:
()
SW M E V
SW DV W
=−
(10.2)
where SW is left ventricular stroke work, E
DV
is end-diastolic volume, and V
W
, the
x-axis intercept, is the extrapolated end-diastolic volume at which the external
stroke work is zero.
Another advantage of PRSW is that it diminishes at a faster rate with reduction
in preload compared with end-systolic pressure and dp/dt, therefore giving rise to a
greater range of values [37]. As a result, the preload recruitable stroke work rela-
tionship or M
SW
is much more reproducible and robust than ESPVR and maximum
dp/dt to end-diastolic volume relationship. Furthermore, Takeuchi et al. [38] sug-
gested that PRSWR was a more linear and reliable indicator of left ventricular con-
tractility in man than ESPVR, because the latter tended to change with variations in
afterload, whereas PRSWR remained unchanged. A potential drawback of PRSWR
in assessing systolic function is that it does not separate systolic performance from
diastolic performance as the whole pressure-volume loop is taken into consideration
in deriving the PRSW.
The derivation of both ESVPR and PRSW involves manipulation of loading
conditions, either by means of transient occlusion of the inferior vena cava or by
pharmacological means. This may prove to be cumbersome; therefore, various
investigators have attempted to derive ESPVR [39] and PRSWR [40] with data
obtained from a single heartbeat. The basic principle of single-beat determination of
PRSW is that V
W
in (10.2) has been found to be essentially constant in an individual
regardless of any short-term changes in the loading or inotropic conditions [37]. It is
then apparent from the equation that M
SW
can be calculated once the value of V
W
is
known for that particular individual without the need for loading condition manip-
ulation. In a canine model, Karunanithi et al. [40] validated single-beat measure-
ment of PRSW against multiple-beat measurements and found excellent
correlations. Furthermore, the authors found that single-beat determination of
PRSW was less load dependent and more reliable and more reproducible than other
single-beat measurements such as single-beat elastance. However, more widespread
use of these methods, especially in the clinical settings, is still pending.
10.2.4 Left Ventricular Stress Strain Relationship
Another approach to assess myocardial contractility is to measure the amount of
myocardial shortening in relation to the force resisting such shortening (i.e., the
afterload). The left ventricular end-systolic wall stress is usually considered a reli-
able estimate of afterload, and various measures, such as EF and fractional shorten
-
ing, have been used as markers of myocardial shortening. If the myocardial fiber
256 Echocardiography: A Tool for LVSD Identification
shortening on the y-axis is plotted against end-systolic wall stress on the x-axis, a
more or less linear inverse relationship is seen [41]. An upward shift of this relation-
ship is seen with increased contractility, for example, with dobutamine infusion
[41]. A decrease in ejection fraction as a result of increased afterload, such as that
seen in aortic stenosis, is not considered a result of impaired contractility, because
there is no shift in the end-systolic wall stress to EF relationship. Instead, it is seen as
a result of afterload mismatch.
An obvious advantage of the left ventricular stress strain relationship over
ESPVR is that the former takes into account ventricular geometry and muscle mass.
This will be advantageous in situations of chronic alterations in loading conditions
such as those seen in valvular heart disease. Another advantage of assessing end-
systolic wall stress is that it can be estimated noninvasively with echocardiography
[3]. End-systolic wall stress is related directly to systolic blood pressure and left ven-
tricular end-systolic dimension and is inversely related to wall thickness in end
systole.
10.3 Echocardiographic Examinations
Comprehensive echocardiographic examinations were performed on study
patients. Echocardiographic examinations were performed using commercially
available equipment (Hewlett Packard Sonos 2500, 5500, Chennai, India). Second
harmonic imaging was used in all later studies on the Sonos 5500. All
echocardiographic studies were recorded on VHS videotapes. These recordings
were converted into individual frames of bitmap images using the video capture
card Pinnacle Mp30. All echocardiographic examinations were performed from
standard views with the patients in a left lateral decubitus position. The standard
views included parasternal long- and short-axis views, the apical four- and
two-chamber views, and subcostal views. From the parasternal long-axis view,
M-mode measurements, including left ventricular end-systolic, end-diastolic dimen-
sions, and left ventricular posterior wall thickness in end systole, were measured
(Figure 10.6). For patients where properly aligned M-mode dimensions could not
be measured, 2-D guided measurements were used. Left ventricular outflow tract
diameters were also measured in this view, using the zoom function to magnify the
views when appropriate.
From the apical four-chamber view, left ventricular end-diastolic and end-sys-
tolic volumes were measured using the modified Simpson’s rule [42]. Continuous
and pulsed wave Doppler examination of the mitral inflow was performed at the
10.3 Echocardiographic Examinations 257
Figure 10.6 Parasternal long-axis view for measurements. EDD, end-diastolic dimension; ESD,
end-systolic dimension; LVPW, left ventricular posterior wall thickness in end systole.
apical four-chamber view with the sampling volume placed at the tips of the mitral
valve leaflets. The mitral leaflets were carefully imaged and examined in all views to
ascertain the mechanisms and the degree of mitral regurgitation. The severity of
mitral regurgitation was graded semiquantitatively according to the criteria of
Helmcke et al. [43].
10.3.1 Echocardiographic Measurements and Calculations
10.3.1.1 Echocardiographic Measurement of Left Ventricular Volume
Left ventricular diastolic and systolic volumes were measured from the apical
four-chamber view according to the modified Simpson’s rule (Figure 10.7). The
endocardial border was traced excluding the papillary muscles. The single-plane
method was used in all studies except for patients with functional mitral regurgita-
tion; for those patients, a biplane method was used. The use of the biplane method
in these patients with coronary artery disease resulted in more accurate estimation
of left ventricular volumes as the enlargement of the left ventricle may be
asymmetrical.
Only representative cycles were measured and the average of at least three mea-
surements was taken. The frame captured at the R wave of the electrocardiogram
was considered the end-diastolic frame, and the frame with the smallest left ventric-
ular cavity was considered the end-systolic frame. The end-diastolic and end-sys-
tolic volumes were normalized to the body surface area to give the respective index.
The EF was calculated from the left ventricular end-systolic and end-diastolic
volume.
According to Simpson’s rule, the volume of the large figure is the sum of the vol-
umes of a series of similar, smaller figures. The Simpson method is sometimes
referred to as the disc summation method because the left ventricle is assumed to be
made up of a series of discs stacked on top of each other. The Simpson method is
attractive because it does not require the ventricle to conform to any particular
shape or geometry. A simplified model Simpson’s rule, which used only images from
the apical four-chamber view, has been used [44]. In a study by Erbel et al. [44], esti-
mation of left ventricular volume by the single-plane disc method yielded accurate
results compared with direct volume measurements only in left ventricles without
asymmetry. For asymmetric hearts, such as those seen with coronary artery disease
and previous myocardial infarction, the biplane disc method was more accurate
than the single-plane method. The volumes measured for a normal subject and one
with systolic dysfunction subject are shown in Figure 10.8.
258 Echocardiography: A Tool for LVSD Identification
(a) (b)
Figure 10.7 Measurement of left ventricular volume: (a) single-plane method and (b) biplane
method.
Interobserver and Intraobserver Variability
To determine the interobserver variability in measuring left ventricular volumes, we
randomly selected 10 studies each from the resting phase, immediate postexercise
phase, and postoperative phase. Two experienced observers measured the left ven-
tricular end-systolic and end-diastolic volumes. The interobserver variability was
measured by the mean difference of the two measurements ± the standard deviation.
Pearson’s correlation coefficients between the two measurements were also calcu-
lated. To determine the intraobserver variability, one single observer measured the
ventricular volumes on 10 randomly selected sets of images on two occasions. The
intraobserver variability was measured by the mean difference of the two measure-
ments ± the standard deviation. The correlation coefficients between the two mea-
surements were also calculated. The interobserver variability in the measurement of
resting left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV)
was 3 ± 8.5 mL (r = 0.98) and 0.7 ± 8.2 mL (r = 0.94), respectively, corresponding to
a variability in resting EF of 0 ± 5%. Immediately after exercise, the variability was
1.2 ± 14.5 mL for EDV (r = 0.94), −1.8 ± 4.7 mL for ESV (r = 0.96), and 1 ± 3% for
EF. After surgery, it was −1.5 ± 5.7 mL for EDV (r = 0.99), 2 ± 9.2 mL for ESV (r =
0.97), and 0 ± 5% for EF.
The intraobserver variability in the measurement of resting left ventricular EDV
and ESV was 4.9 ± 10.4 mL (r = 0.97) and −0.9 ± 3.5 mL (r = 0.99), respectively,
corresponding to a variability in ejection fraction of −2 ± 4%. Immediately after
exercise, variability was -0.8 ± 9.5 mL for EDV (r = 0.98), −0.9 ± 3.2 mL for ESV (r
= 0.99), and −1 ± 2% for EF. Postoperatively, it was −2.4 ± 6.3 mL for EDV (r =
0.99), −1.2 ± 4.1 mL for ESV (r = 0.99), and 1 ± 3% for EF.
The interobserver and intraobserver variability in the measurement of left ven-
tricular volumes should be evaluated. Measurement of ventricular volumes and
ejection
fraction has
been reported to show significant variability [45]. In a study by
Himelman et al. [45], the variability in the estimation EF was 7%, whereas the vari-
ability in the estimation of ventricular volumes was up to 10%. The variability in
these measurements could be acknowledged by taking the average of at least three
measurements for each of the parameters assessed.
10.3 Echocardiographic Examinations 259
30
Volume (ml)
40
50
60
70
80
90
100
110
Biplane method
Area-length method
Biplane method
Area-length method
01020
30
40 50
Frame no.
60 70 80 90
120
Volume (ml)
125
130
135
140
145
150
155
01020
30
40 50
Frame no.
60 70
Figure 10.8 Volume variation in (a) normal and (b) systolic dysfunction.
10.3.1.2 Left Ventricular dp/dt
The maximum rate of rise of left ventricular pressure during the isovolumetric con-
traction phase (left ventricular dp/dt) has been used as an indicator of left ventricular
contractility. It can be measured echocardiographically in the presence of mitral
regurgitation by continuous-wave Doppler examination of the mitral regurgitant jet
[10]. From the apical four-chamber view, continuous-wave Doppler examination of
the mitral regurgitant jet was performed. The time taken for the velocity of the
mitral regurgitant jet to increase from 1 to 3 m/s was measured from the spectral dis-
play (Figure 10.9). Assuming an unchanged left atrial pressure, the rise in
intraventricular pressure associated with an increase of mitral regurgitant jet veloc-
ity from 1 to 3 m/s would be 32 mmHg. The left ventricular dp/dt in mmHg/s was
given by dividing 32 mmHg by the measured time interval. Continuous-wave Dopp-
ler examination of the mitral regurgitant jet with a clear envelope on the spectral dis-
play was not possible in all patients because it required proper alignment of the
regurgitant jet and the Doppler beam. This is difficult and sometimes impossible in
the presence of a very eccentric regurgitant jet such as that seen in patients with
mitral valve prolapses or flail mitral leaflets.
Continuous-wave Doppler examination of the mitral regurgitant jet from the
apical four-chamber view. The time it takes for the mitral regurgitant jet velocity to
increase from 1 to 3 m/s can be measured from the spectral display. In this example,
the time interval is 20 ms; therefore, the left ventricular dp/dt is 32 mmHg/0.02 sec-
ond, that is, 1600 mmHg/s.
10.3.1.3 Left Ventricular End-Systolic Wall Stress
Left ventricular end systolic wall stress (ESWS) at rest was calculated from
noninvasively obtained parameters from
ESWS
BPsys LVESD
PWsys
PWsys
LVESD
=
+
⎡
⎣
⎢
⎤
⎦
⎥
0334
1
.
which has been validated by [3]. BPsys is the resting systolic blood pressure measured
by a sphygmomanometer in mmHg, LVESD is the left ventricular end systolic dimen-
sion and PWsys is the posterior left ventricular wall thickness measured
echocardiographically at end systole from the parasternal long-axis view. The aver-
age of three measurements was taken.
260 Echocardiography: A Tool for LVSD Identification
Figure 10.9 Measurement of left ventricular dp/dt.
10.3.1.4 Left Ventricular Forward Stroke Volume and Cardiac Output
Pulsed wave examination of the left ventricular outflow tract was performed from
the apical four-chamber view with the sampling volume placed just below the aortic
valve. The time velocity integral (in centimeters) was obtained from the spectral dis-
play by tracing the modal velocity (Figure 10.10). The diameter of the left ventricu-
lar outflow tract was measured from the parasternal long-axis view. The cross
section of the left ventricular outflow tract was assumed to be circular, and the area
calculated from the radius accordingly. The left ventricular forward stroke volume
was obtained by determining the product of the cross-sectional area and the time
velocity integral. The cardiac output was given by the productof the forward stroke
volume and the heart rate. Resting cardiac output was calculated with these param-
eters measured at rest, and maximum exercise cardiac output was calculated with
the same parameters measured at peak exercise or immediately afterward.
10.3.1.5 Mitral Regurgitant Volume
Mitral regurgitant volume can be estimated echocardiographically. Mitral
regurgitant volume can be calculated as the difference between left ventricular for-
ward stroke volume in systole and the total mitral inflow volume in diastole. More
recently, the proximal convergence method in calculating mitral regurgitant volume
has been used with increasing popularity [10, 46]. It has been shown that the proxi-
mal flow convergence method is associated with a significant overestimation of
mitral regurgitant volume when the proximal flow acceleration field is constrained
and that a geometric correction is necessary for accurate estimation [47].
A proximal flow acceleration field constraint was commonly seen in patients
with mitral valve prolapse or flail mitral leaflets. Furthermore, proper visualization
of the proximal flow acceleration field immediately after exercise was almost
impossible. As a result, estimation of mitral regurgitant volume immediately after
exercise was not possible with the proximal flow convergence method. In the
method used by Blumlein et al. [48], mitral regurgitant volume was obtained by the
difference between the total stroke volume and the left ventricular forward stroke
volume. The total stroke volume was given by the difference between the left ven-
tricular end-diastolic and end-systolic volumes obtained from the apical four-cham-
ber view. Because the total stroke volumes and the left ventricular forward stroke
volumes were measured both at rest and immediately after exercise, the mitral
regurgitant volumes could be estimated in the resting and exercise states.
10.3 Echocardiographic Examinations 261
Figure 10.10 Measurement of left ventricular outflow tract time velocity integral.
10.3.1.6 Wall Motion Index
Wall motion scoring is based on a systematic visual judgment of the LV wall motion.
In each echocardiographic imaging plane, the LV wall is 16 divided into several seg-
ments. Segmental models involving between 5 and 20 segments have been described
[42, 49–52]. Each segment is assigned a numerical value that indicates the degree of
wall contraction. In previous recommendations the endocardial motion of a seg-
ment was the only property to be rated [44]. However, recent guidelines from the
American Society of Echocardiography (ASE) recommend that the systolic thicken-
ing of a segment, in addition to its endocardial motion, be evaluated [53]. The ASE
standard assigns a score of 1 for normal contraction, 2 for hypokinesia, 3 for
akinesia, 4 for dyskinesia, and 5 for aneurysmal bulging. Berning et al. proposed a
reverted scoring system in which a lower score indicated worse function and, in
addition, they included a score for hyperkinetic motion and excluded the
aneurysmal score (+3 = hyperkinesia, +2 = normokinesia, +1 = hypokinesia, 0 =
akinesia, −1 = dyskinesia) [54]. A global wall motion score, referred to as the wall
motion index (WMI), can be calculated by averaging the readings in all segments.
The WMI has shown good correlation with the LVEF as measured by radionuclide
angiography (RNA) or contrast ventriculography, and the agreement with the refer-
ence method was comparable to that for the Simpson-LVEF or visual estimations of
the LVEF [55].Several studies have reported a strong prognostic performance by the
WMI (obtained according to ASE or Berning) in terms of mortality or cardiac events
in patients with heart failure or acute myocardial infarction [56, 57].
10.3.1.7 Mitral Annulus Motion
The mitral annulus is part of the fibrous skeleton of the heart and consists of a ring
of collagenous tissue that surrounds and supports the left atrioventricular orifice
[58]. It forms the attachment of the mitral valve leaflets and myocardial fibers of the
LV and left atrium. The contraction of longitudinal/oblique LV myocardial fibers
pulls the mitral annulus in a caudal direction toward the apex. Moreover, the myo-
cardial tissue volume is regarded as noncompressible and the total volume of the
heart is fairly constant during the entire heart cycle [59].
The displacement of myocardial tissue toward the apex caused by long-axis
shortening will therefore inevitably cause a volume reduction of the inner LV diame-
ter, in addition to the volume reduction caused by the annular excursion. The
long-axis shortening of the LV can be evaluated by M-mode echocardiography as
the maximum amplitude of mitral annulus motion (MAM). Measuring MAM is
easy to learn and rapid to perform, even in patients with poor image quality, and it
has advantageous reproducibility [60]. The amplitude of MAM is load dependent,
which has to be considered when it is used for evaluations of LV systolic function.
Early studies of the maximum amplitude of MAM revealed a high correlation with
the LVEF, and MAM was therefore proposed as an LVEF surrogate [61].
10.3.2 Real-Time Left Ventricular Volume by Automated Boundary Detection
Real-time online measurement of left ventricular volume during the cardiac cycle
can be performed by using the automated boundary detection algorithm (Acoustic
262 Echocardiography: A Tool for LVSD Identification
Quantification, Agilent, Andover, Massachusetts). The study was performed from
the apical four-chamber view in the second-harmonic mode. The depth of the imag-
ing was minimized to ensure that as large an image of the left ventricle as possible
was obtained. An artifact-free electrocardiogram was obtained and the 2-D images
of the left ventricle were optimized by adjusting the overall gain and transmitting
function, time gain compensation, and the lateral gain controls so as to obtain a uni-
formly gray picture. The acoustic quantification function was then activated.
Further fine adjustments of the gain and transmitting function were performed
to ensure proper tracking of the endocardial borders throughout the cardiac cycle
and minimization of noise artifacts within the blood pool of the left ventricle. A
region of interest that included the entire left ventricle was drawn and the long axis
of the left ventricle was determined. Real-time display of ventricular volumes and
EF was then obtained by activating the waveform function. Finally, scaling of the
display was adjusted for optimal display of the waveforms (Figure 10.11).
10.4 Left Ventricle Systolic Dysfunction Identification
In 2003, an automated edge detection algorithm using fuzzy logic for the delinea-
tion of left ventricles was developed. From such delineated left ventricles, the sys-
tolic dysfunction was quantifiedand the region of dysfunctionwas identified [62].
10.4.1 Delineation of Left Ventricle
Each image was preprocessed before doing measurements. Histogram equalization
was performed on each frame to increase the contrast. The speckle noise was
removed by means of a median filter. The mask size used in filtering was 5 × 5. The
greater the mask size, the greater the blur in the image. A Mamdani-type fuzzy
logic–based edge detection algorithm was framed to detect the left ventricle con-
tours. It has eight inputs and one output, with three member functions each at the
input side and two member functions at the output side. Gaussian filters were
adopted for all membership functions (Figure 10.12).
The function adopted to implement the AND and OR operations were the mini-
mum and maximum functions, respectively. The Mamdani method was chosen as
10.4 Left Ventricle Systolic Dysfunction Identification 263
Figure 10.11 Real-time left ventricular volume by automated boundary detection. The region of
interest is drawn around the left ventricle in the apical four-chamber view. The real-time ventricu
-
lar volume and EF are displayed on the bottom right-hand corner of the display and the waveform
is displayed together with the electrocardiogram.