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LABORATORY INVESTIGATION
VENTRICULAR PERFORMANCE
The influence of preload and heart rate on Doppler
echocardiographic indexes of left ventricular
performance: comparison with invasive indexes in
an experimental preparation
KENNETH WALLMEYER, M.D., L. SAMUEL WANN, M.D., KIRAN B. SAGAR, M.D.,
JOHN KALBFLEISCH, PH.D., AND H. SIDNEY KLOPFENSTEIN, M.D., PH.D.
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ABSTRACT We evaluated the ability of Doppler echocardiography to assess left ventricular performance in six open-chest dogs studied under various conditions. Intravenous infusions of nitroglycerin were used to vary preload, atrial pacing was used to control heart rate, and changes in inotropic state
were induced by two different doses of dobutamine (5 and 10 ,g/kg/min iv) and by administration of
propranolol (1 mg/kg iv). Left ventricular anterior wall myocardial segment length was used as an
index of preload. Maximum aortic blood flow, peak acceleration of aortic blood flow, and dP/dt were
measured with an electromagnetic flow probe around the ascending aorta and a high-fidelity pressure
transducer in the left ventricle. A continuous-wave Doppler transducer applied to the aortic arch was
used to measure peak aortic blood velocity, mean acceleration, time to peak velocity, and the systolic
velocity integral. The differences between mean values obtained under different inotropic conditions
were significant at the p < .01 level for peak velocity and at the p < .05 level for mean acceleration.
Within a given animal, Doppler measurements of peak velocity correlated very closely with maximum
aortic flow (r = .96), maximum acceleration of aortic flow (r = .95), and with maximum dP/dt (r =
.92). Mean acceleration measured by Doppler echocardiography also correlated very closely with
conventional indexes, but was subject to greater interobserver variability. Doppler measurements of
time to peak and the systolic velocity integral correlated less well with conventional hemodynamic
indexes. In conclusion, Doppler measurements of peak aortic blood velocity and mean acceleration
offer an effective means to noninvasively assess short-term changes in left ventricular performance
under conditions of varying preload, heart rate, and inotropic state.
Circulation 74, No. 1, 181-186, 1986.
THE ASSESSMENT of left ventricular performance is
of key importance in determining the presence and
prognosis of many forms of heart disease, and in monitoring the effectiveness of therapeutic interventions.
Conventional invasive techniques are limited by high
cost, the risk to the patient of complications, and technical difficulties in assessing performance during dynamic states such as exercise. These limitations become particularly important in the context of the serial
determinations required to monitor the course of disease or response to therapy.
From the Cardiology Division, Department of Medicine, Medical
College of Wisconsin, and Zablocki Veterans Administration Medical
Center, Milwaukee.
Supported in part by grants from the National Heart, Lung, and Blood
Institute, National Institutes of Health, the Veterans Administration, the
American Heart Association, and the Heath Foundation.
Address for correspondence: H. Sidney Klopfenstein, M.D., Ph.D.,
Cardiology Division, Medical College of Wisconsin, 8700 W. Wisconsin Ave., Milwaukee, WI 53226.
Received Feb. 25, 1986; accepted April 4, 1986.
Vol. 74, No. 1, July 1986
The potential use of measurements of aortic blood
acceleration and peak velocity as indexes of ventricular performance in patients with heart disease was suggested by Rushmer' more than 20 years ago. Since
then, invasive studies have demonstrated the sensitivity of maximum acceleration of aortic blood flow
(dQ/dt) to depressed ventricular function caused by
coronary occlusion,2 acute myocardial infarction,3 and
the administration of propranolol.4 The development
of Doppler echocardiography now offers a reliable
method with which to measure aortic blood flow velocity and acceleration noninvasively.9- Clinical studies
have suggested its use in the management of critically
ill patients,9 and in the identification of left ventricular
dysfunction in patients during exercise.,101
Validation of Doppler echocardiography as a useful
tool in assessment of ventricular performance depends
on the demonstration of the sensitivity of Doppler measurements to changes in contractility, and on an appre181
WALLMEYER et al.
ciation of the degree to which these measurements are
influenced by preload, afterload, and heart rate. The
current study was undertaken to define the relationship
between Doppler echocardiographic measurements related to the ascending aortic blood velocity and the
more conventional indexes left ventricular dP/dt.
maximum aortic blood flow (Qmax) and maximum
dQ/dt under varying conditions of preload, heart rate,
and inotropic state.
O^
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182
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Methods
Six mongrel dogs weighing 23.6 to 33.0 kg were screened for
parasites, fasted overnight, and anesthetized with intravenous
administration of an ae-chloralose and urethane solution. The
dogs were then intubated and ventilated by a volume respirator
(Harvard Apparatus Co.) with the use of air enriched with oxygen (5 liters/min), and a thoracotomy was performed in the left
fifth intercostal space of each. Polyvinyl catheters (Tygon Microbore Tubing, 0.05 inch inside diameter; Norton Plastics)
were introduced into the right atrium via the internal thoracic
vein, into the left atrium through a purse-string suture, and into
a femoral artery, and were connected to fluid-filled Statham
P23Db pressure transducers (Statham Instrument Co.), with the
zero pressure reference point at mid right atrial level. A micromanometer-tipped catheter (Millar Instruments) was advanced
to the ascending aorta via the internal thoracic artery for ieasurement of aortic blood pressure. An electromagnetic flow
probe (Howell Instrument Co.) was placed around the ascending aorta and blood flow was measured with a Narcomatic
flowmeter (Model RT-500, Narco Biosystems). 12 A micromanometer (Konigsberg Instruments) was inserted into the left
ventricle through an apical stab wound and secured with a
purse-string suture. Two sonomicrometer crystals (Vernitron
Piezoelectric Division, PZT5A, flat and cyclinder) were inserted into the anterior left ventricular free wall at midmyocardial
level perpendicular to the long axis of the heart, and the distance
between them was measured (Hartley Multichannel Flow-Dimension System) as an index of preload. Pacing wires were
sutured to the left atrium, and a hydraulic occluder was placed
on the descending thoracic aorta to allow maintenance of aortic
blood pressure if needed. The electrocardiogram was monitored
throughout, and arterial blood gases were measured at intervals
of 1 hr and were maintained in the normal range.
All hemodynamic measurements were made under steadystate conditions with mechanical ventilation for 15 to 30 sec
suspended to eliminate respiratory variation. Hemodynamic
data were recorded on an analog FM tape recorder (A. R. Vetter
Co.) and on an eight-channel strip-chart recorder (Gould Model
2800). Ten second data files were subsequently transferred to a
digital computer (DEC LSI 11/23) and sequential interactive
programs were used to calculate QM1X maximum dQ/dt, and
maximum left ventricular dP/dt. Simultaneously with the collection of hemodynamic data, Doppler measurements of blood
velocity were obtained in the continuous mode with a dedicated
nonimaging Doppler transducer (Pedof) with a 2 MHz carrier
frequency (Irex IIIB, Johnson & Johnson), and recorded on a
strip-chart recorder at a paper speed of 50 mm/sec. The transducer was hand held and applied to the aortic arch. The ultrasonic beam was oriented parallel to ascending aortic blood flow,
guided by audio and graphic signals to obtain maximal Doppler
shift with velocity envelopes having distinct borders. Doppler
measurements of peak blood velocity (PV), time to peak velocity (TTP), and mean acceleration (A PV/TTP) were made for
6 consecutive beats (figure 1) and averaged. The systolic veloc-
V~O,VIII..
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9
r-10*111.
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k,'a
1
k&
.
..
1,
FIGURE 1. A representative recording of the electrocardiogram, analog Doppler signal, and Doppler velocity envelope, illustrating the
method of Doppler measurement. Velocity calibration I= m/sec. ET
= ejection time. Mean acceleration was calculated as PVfTTP.
ity integral (SVI) was calculated as the product of mean velocity
and ejection time, and was determined for a single representative beat. Doppler measurements were made by two observers
and the data were averaged.
With the animals in the baseline contractile state, measurements were obtained before the administration of drugs, both at
resting heart rate and with rapid atrial pacing (resting heart rate
+ 40 beats/min). The infusion of nitroglycerin was begun at
100 gg/gin iv, and was increased to 200 gg/min if necessary to
produce a greater than 2.5% decrease in end-diastolic myocardial segment length. Measurements were then obtained in dogs in
sinus rhythm and during rapid atrial pacing. A simultaneous
infusion of dobutamine was begun, and data were collected at
infusion rates of 5 and at 10 gg/kg/min with the animals in sinus
rhythm. The infusion of nitroglycerin was then discontinued,
allowing segment length to increase. Measurements were then
made sequentially at 10 gg/kg/min and 5 gg/kg/min dobutamine and in the control state, with and without rapid atrial
pacing. Finally, propranolol was administered (1 mg/kg iv) and
data were collected in dogs in sinus rhythm and, if tolerated,
during rapid atrial pacing. Data were collected after a steady
state had been maintained for at least 5 min. Data files in which
pulsus altemans occurred were excluded from analysis.
For each animal studied, the values for each index of contractility obtained in each inotropic state were averaged. These
within-animal means were themselves averaged to give equal
weight to each animal, and the differences between states were
CIRCULATION
LABORATORY INVESTIGATION-VENTRICULAR PERFORMANCE
tested by analysis of variance. When the analysis of variance F
test was significant, the least significant difference test was also
applied. The comparison of adjacent experimental conditions
was performed with the paired t test of the mean values. Linear
regression and correlation analysis was performed to relate the
four Doppler-derived indexes with the three invasively measured indexes for each of the six data sets. The pooled withinanimal correlation coefficient was computed with Fisher's Z
transformation. 13 Each of these correlations was also adjusted
for heart rate and segment length by calculating the partial
correlation coefficients to control for the possible influence of
these factors on the correlations. The interobserver variability
for each Doppler measurement was calculated as a percentage
difference for each set of observations and is illustrated as a
histogram.
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Results
Data adequate for analysis were obtained from all
animals studied. Preload as measured by end-diastolic
segment length varied from - 6% to + 8% of the baseline value; this corresponded to decreases of up to
4 mm Hg and increases of up to 6 mm Hg from baseline in mean left atrial blood pressure. Mean and standard deviation of measured mean arterial blood pressure and mean left atrial blood pressure for all data files
were 120 ± 20 and 6.9 + 4.2 mm Hg, respectively.
The effect of changes in inotropic state on the Doppler
echocardiographic recordings in a representative animal are illustrated in figure 2. The most apparent difference between the recordings was the change in the
height of the envelopes, reflecting alterations in PV.
The expected changes in the ejection time and TTP
were also present, but were less obvious. Changes in
mean acceleration and the SVI were for the most part
reflective of changes in the PV.
The mean values of all index measurements in all
animals calculated for each inotropic state are presented in table 1, with comparisons by paired t tests of
values obtained in adjacent inotropic states. Differences in the values of PV obtained with alterations in
contractility were significant at the p < .01 level, and
those for acceleration were significant at the p < .05
level. Changes in TTP and SVI in dogs in different
inotropic states varied.
The relationships between each of the Doppler-derived indexes of ventricular function and the conventional invasively derived indexes are presented in table
2, and the specific correlation between PV and Qmax
is illustrated in figure 3. PV was found to correlate
.96), with dQ/dt
very closely with Qmax (r
(r = .95), and with dP/dt (r .92). Mean acceleration
correlated best with dQ/dt (r -.92), but also correlated closely with Qmax and with dP/dt (r = .90 and .91,
respectively). The correlations of the SVI with the
conventional indexes were less significant. The poorest correlations were between TTP and the invasive
indexes. When the regression analysis of Doppler vs
invasive indexes was repeated after adjustment for the
effect of heart rate and variations in preload, the resulting correlation coefficients were essentially unchanged
from those obtained before adjustment.
The analysis of interobserver variability is summarized in figure 4. The measurement of PV was associated with the least interobserver variability, with a
mean difference between observers of only 3.7%. Differences between observers were most problematic in
_±
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.. . ..
CONTROL
DOBUTAMINE PROPRANOLOL
mr/sece
FIGURE 2. Doppler recordings and simultaneous
electrocardiogram taken from a representative animal in the control state, during the infusion of dobutamine (10 gg/kg/min iv), and after administration of
propranolol (1 mg/kg iv).
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Vol. 74, No. 1, July 1986
183
WALLMEYER et al.
TABLE 1
Mean ± SD values for each index under each inotropic condition
Doppler indexes
Control
Peak
Invasive indexes
Max
Max
PV
(m/sec)
Acceleration
(m/sec2)
TTP
(msec)
SVI
flow
dQ/dt
(mm)
(1/m)
(1/min/sec)
dP/dt
(mm Hg/sec)
1.55 0.34
42.2 22.7
69.0 ± 18.9
132 ± 31
15.5 3.1
356 ± 119
2672 ±706
1.87+0.44
(p<.Ol)
57.4+27.4
(p<.O5)
61.6±12.2
144±41
21.2+4.3
515±151
1.87 ± 0.44
57.4 ± 27.4
(NS)
61.6 ± 12.2
(NS)
144 ±41
(p<.005)
21.2 ± 4.3
(p<.01)
515 ± 151
4041+686
(p<.02)
4041 ± 686
2.31 ± 0.47
77.4 ± 26.6
56.3 ± 11.8
169 ±44
26.5 ± 6.5
716 ± 218
5293 ±700
(p<.0l)
(p<.05)
(NS)
(p<.01)
(p<.02)
(p<.02)
(p<.01)
1.55 ± 0.34
42.2 ± 22.7
69.0 ± 18.9
132 ± 31
15.5 ± 3.1
356 ± 119
2672 ±706
1.03 ±0.15
(p<.01)
20.3 ± 5.4
(p<.02)
87.5 ± 17.2
(p<.02)
97 ± 20
10.1 ± 2.3
(p<.005)
209 ± 55
(p<.005)
1435 ± 271
(p<.05)
vs
Dobutamine, 5 ,ug/kg/min
Dobutamine, 5
1£g/kg/min
vs
10 ,mg/kg/min
Control
vs
Propranolol, 1 mg/kg
(p<.005)
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The level of significance for t tests between values in adjacent inotropic states are given in parentheses. Measurements obtained with and without
infusion of nitroglycerin are pooled for each inotropic state.
the determination of TTP, where the difference between observers averaged 14.8%. Since mean acceleration is calculated as PV/TTP, it reflects the interobserver variability for the determination of TTP, with a
mean difference between observers of 16.8%. The
mean interobserver difference for SVI was 10.7%.
Discussion
The results of the current study demonstrate that
Doppler echocardiographic measurements of ascending aortic blood velocity are very sensitive to changes
in left ventricular systolic performance. That PV and
mean acceleration are more sensitive than the TTP or
the SVI is demonstrated by their superior ability to
detect differences in inotropic states and by their better
correlations with conventional invasive indexes. The
finding that these correlations were not appreciably
affected by adjustment for heart rate or preload suggests that the Doppler indexes are no more influenced
by these variables than are the conventional invasive
indexes studied.
Some overlap of index measurement in different
states was noted for each Doppler and conventional
index studied, and may be partially attributed to variation between animals with respect to responses to the
agents used to alter contractility and to the fact that the
range of variation in preload differed between animals.
Doppler indexes share the basic limitation of all indexes of ventricular function, namely that they do not
measure contractility directly. Thus, while we have
found Doppler measurements of aortic PV and mean
acceleration to be as sensitive as conventional indexes
184
to changes in contractility, they are no better than
conventional indexes in defining inotropic state in an
absolute way and are not practical for comparison of
contractile states between individuals. This limitation
of Doppler indexes of function has been described by
others,8' 14 and suggests that the value of this technique
lies in its ability to detect changes in ventricular function in a given individual.
Early investigations of aortic blood velocity using
TABLE 2
Correlations between Doppler (horizontal rows) and invasively derived (vertical columns) indexes of left ventricular function for all
six animals studied
Q max
dQ/dt
Max
dP/dt
.96
.95
.94
.95
.94
.93
.92
.91
.89
.90
.88
.87
.92
.91
.91
.91
.88
.88
-.67
-.60
-.56
-.70
-.63
-.61
-.70
-.61
-.63
.79
.83
.78
.75
.80
.72
.69
.76
.64
Max
PV
r
r(HR)
r(SL)
Acceleration
r
r(HR)
r(SL)
TrP
r
r(HR)
r(SL)
svi
r
r(HR)
r(SL)
r = correlation coefficient for variables indicated by row and column
heading; r(HR) = partial correlation coefficient adjusted for heart rate;
r(SL) = partial correlation coeficient adjusted for segment length.
CIRCULATION
LABORATORY INVESTIGATION-VENTRICULAR PERFORMANCE
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=.96
~~~~~~~r
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45
25
30 35 401
15
20
011 1 1 1 1 1
PEAK FLOW (I/miN)
Relationship between Doppler-determined aortic PV and QmVA (electromagnetic flowmeter) is shown for each of six
5
0
0- F 1
10
1
FIGURE 3.
animals. The pooled co'rrelation coefficient without adjustment for heart rate or changes in preload was .96.
1 0A £=~~A
10
110-
|
A
--
~~PEAK VELOCITY
5-
TIME TO PEAK
10 2004A0078
>
~
~
00102104
~ ~ ECNTDFEEC
BETWENCTOEOBERVERTALUE
FIGURE 4. Histogram illustrating percent difference between two observers for individual measurements of each Doppler
index.
Vol. 74, No. 1, July 1986
185
WALLMEYER et al.
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catheter-tipped velocity probes found maximum acceleration to be the most sensitive index of function.`'
The Doppler technique that we used differs in that it
measures mean rather than maximum acceleration.
This difference may account for the fact that we found
acceleration to be somewhat less sensitive than PV in
detecting changes in inotropic state. Prior work evaluating Doppler echocardiographic assessment of left
ventricular function has focused on the agreement of
Doppler measurements with ejection fraction values'1' 15 and, when combined with determination of
aortic cross-sectional area, with results of traditional
methods of measuring cardiac output. Ejection fraction and cardiac output are strongly influenced by loading conditions, however. It is encouraging that Doppler measurements of PV and mean acceleration are
highly sensitive to changes in contractile state over the
range of preload likely to be encountered clinically.
The need to make our measurements under stable
hemodynamic conditions in different inotropic states
precluded variation of both preload and afterload in a
single study. Further studies are therefore required to
evaluate the effect of afterload on Doppler indexes of
left ventricular performance, and to help identify the
Doppler index that best reflects changes in contractility
in settings in which afterload is not constant. Further
studies are also needed to confirm work with cathetertipped velocity probes demonstrating the sensitivity of
aortic blood flow velocity and acceleration to changes
in regional as well as global ventricular function.
The most important technical problem encountered
in making Doppler measurements was the occasional
difficulty in correctly identifying the onset and termination of ventricular ejection, events that are sometimes obscured by baseline artifacts. As the histogram
demonstrated (figure 4), the relatively higher mean
differences between observers for time-dependent
Doppler indexes (acceleration, TTP, and SVI) resulted
from proportionately large differences on only a few
occasions. Predictably, these instances occurred when
the heart rate was very high and TTP and ejection time
were short. Further developments in instrumentation
may result in more reproducible recordings of acceleration or permit accurate measurement of maximum
acceleration, making this measurement more useful.
The finding here that Doppler indexes of left ventricular function are comparable to conventional indexes in their sensitivity to changes in contractility at
varying levels of preload and heart rate lends impetus
to the study of potential clinical uses of this technique.
Productive areas for investigation may include application of Doppler echocardiography to exercise stress
186
testing and to serial evaluation of left ventricular function after therapeutic interventions.
In conclusion, while each of the Doppler indexes
studied showed significant correlation with conventional invasive indexes, peak velocity appears to be the
best of the Doppler indexes, showing the closest correlation with the least interobserver variation. Although
the effect of changes in afterload remains to be defined, the Doppler indexes studied appear no more
dependent on preload or heart rate than are the conventional invasive indexes. Thus, the Doppler echocardiographic determination of ascending aortic blood velocity offers a promising noninvasive method for the
assessment of changes in left ventricular performance
in individuals in a wide variety of clinical situations.
We gratefully acknowledge the technical assistance of Andrea Pernell, B.S., Donna Peterson, B.S., and Dennis Janzer,
M.S.B.E.. and the secretarial assistance of Jessica Provine.
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CIRCULATION
The influence of preload and heart rate on Doppler echocardiographic indexes of left
ventricular performance: comparison with invasive indexes in an experimental
preparation.
K Wallmeyer, L S Wann, K B Sagar, J Kalbfleisch and H S Klopfenstein
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Circulation. 1986;74:181-186
doi: 10.1161/01.CIR.74.1.181
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1986 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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