Download Assessment of left ventricular diastolic function by early diastolic

J Appl Physiol 100: 679 – 684, 2006.
First published September 29, 2005; doi:10.1152/japplphysiol.00671.2005.
Assessment of left ventricular diastolic function by early diastolic mitral
annulus peak acceleration rate: experimental studies and clinical application
Qinyun Ruan,1 Liyun Rao,3 Katherine J. Middleton,2 Dirar S. Khoury,3 and Sherif F. Nagueh2
1
First Affiliated Hospital of Fujian Medical University, Fuzhou, China; and 2Methodist DeBakey Heart Center
and 3Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
Submitted 6 June 2005; accepted in final form 28 September 2005
Its clinical utility, however, was not examined. We therefore
sought to examine the hemodynamic determinants of the peak
acceleration rate of Ea in experimental studies and to assess its
clinical application in consecutive patients, including those
referred for right heart catheterization.
METHODS
Animal Studies
(LV) diastolic function plays an important
role in determining LV filling pressures and pulmonary congestion symptoms (14) in patients with and without depressed
LV ejection fraction. Novel noninvasive indexes utilizing tissue Doppler (TD) imaging (TDI) have been recently applied
for the evaluation of LV diastolic function and the prediction of
filling pressures (3, 6, 9 –10). Two of these indexes include
combined measurements of mitral inflow and TD signals of
annular early diastolic excursion (3, 6, 9 –10). The above
methods have the disadvantage of multiple measurements from
different cardiac cycles. A single measurement, if accurate,
could be more applicable clinically. In this regard, a single
measurement of the peak acceleration rate (peak acceleration)
of early diastolic annular velocity (Ea) was shown in an animal
model to provide a good assessment of left atrial pressure (4).
Animal preparation. After the Baylor College of Medicine Animal
Research Committee approved the study, 10 healthy adult mongrel
dogs (weight 19 –28 kg) were anesthetized with pentobarbital sodium
(30 mg/kg), intubated, and mechanically ventilated with an external
respirator. After a midline sternotomy, the heart was exposed, and
after calibration, a high-fidelity 5-Fr pressure catheter (Millar Instruments, Houston, TX) was introduced into the left atrium (LA) through
its appendage. Likewise, to measure LV pressures, a calibrated 5-Fr
12-electrode pressure catheter (Millar) was advanced into the LV by
crossing the aortic valve (positioned along the LV long axis). Surface
electrocardiogram (lead II), atrial, and ventricular pressure signals
were simultaneously acquired on a computer-based data-acquisition
system, and LA and LV pressures were digitized with recordings
acquired at end expiration. The inferior vena cava (IVC) was dissected
and a ring was placed around it to allow for gradual occlusion of the
vein.
Hemodynamic measurements. LV minimal pressure and LVEDP,
maximal instantaneous diastolic transmitral pressure gradient and LA
mean pressure were noted. Also ascertained were the first derivatives
of LV pressure in diastole (⫺dP/dt) and the time constant (␶) of LV
relaxation (13).
Echocardiography. The animals were imaged from the epicardium
by use of an ultrasound system equipped with TDI capability. In the
apical four-chamber view, pulse-wave (PW) Doppler was applied to
record mitral inflow at the valve tips (intraobserver variability for
measuring mitral peak E velocity: 3 ⫾ 1%). The TD program was
applied in PW Doppler to record mitral annular velocities at the septal
and lateral areas (6). The peak velocity of Ea (intraobserver variability
5 ⫾ 2%) at the above sites of the annulus was measured under the
different loading conditions. The time interval between the peak of R
wave and onset of mitral E velocity and between peak of R wave and
onset of Ea at the four areas of the mitral annulus were measured.
Subsequently the difference between these time intervals (TEa-E) was
calculated (10) for each of the four areas and an average value was
derived (intraobserver variability 4 ⫾ 2%, interobserver variability
6 ⫾ 2%).
The peak acceleration rate of Ea velocity was derived by the
computer after the Ea velocity was traced. The computer algorithm
used divided the time from the onset of Ea to its peak into 20 equal
intervals and measured the change in velocity per unit of time in each
interval and reported the highest value (interobserver variability 8 ⫾
Address for reprint requests and other correspondence: S. F. Nagueh,
Methodist DeBakey Heart Center, 6550 Fannin St., Suite 677, Houston, TX
77030 (e-mail: [email protected]).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
heart failure; myocardium; Doppler echocardiography
LEFT VENTRICULAR
http://www. jap.org
8750-7587/06 $8.00 Copyright © 2006 the American Physiological Society
679
Downloaded from http://jap.physiology.org/ by 10.220.32.246 on May 9, 2017
Ruan, Qinyun, Liyun Rao, Katherine J. Middleton, Dirar S. Khoury,
and Sherif F. Nagueh. Assessment of left ventricular diastolic function by
early diastolic mitral annulus peak acceleration rate: experimental studies and
clinical application. J Appl Physiol 100: 679–684, 2006. First published
September 29, 2005; doi:10.1152/japplphysiol.00671.2005.—We sought to
examine the hemodynamic determinants and clinical application of
the peak acceleration rate of early (Ea) diastolic velocity of the mitral
annulus by tissue Doppler. Simultaneous left atrial and left ventricular
(LV) catheterization and Doppler echocardiography were performed
in 10 dogs. Preload was altered using volume infusion and caval
occlusion, whereas myocardial lusitropic state was altered with dobutamine and esmolol. The clinical application was examined in 190
consecutive patients (55 control, 41 impaired relaxation, 46 pseudonormal, and 48 restrictive LV filling). In addition, in 60 consecutive
patients, we examined the relation between it and mean wedge
pressure with simultaneous Doppler echocardiography and right heart
catheterization. In canine studies, a significant positive relation was
present between peak acceleration rate of Ea and transmitral pressure
gradient only in the stages with normal or enhanced LV relaxation, but
with no relation in the stages where the time constant of LV relaxation
(␶) was ⱖ50 ms. Its hemodynamic determinants were ␶, LV minimal
pressure, and transmitral pressure gradient. In clinical studies, peak
acceleration rate of Ea was significantly lower in patients with
impaired LV relaxation irrespective of filling pressures (P ⬍ 0.001)
and with similar accuracy to peak Ea velocity (area under the curve
for septal and lateral peak acceleration rates: both 0.78) in identifying
these patients. No significant relation was observed between peak
acceleration rate and mean wedge pressure. Peak acceleration rate of
Ea appears to be a useful index of LV relaxation but not of filling
pressures and can be applied to identify patients with impaired LV
relaxation irrespective of their filling pressures.
680
LV DIASTOLIC FUNCTION AND ANNULAR ACCELERATION RATE
4%). In an attempt to simplify the measurement of acceleration rate of
Ea, we also calculated the mean acceleration rate as the Ea velocity
divided by acceleration time. Interobserver variability was 6 ⫾ 3%.
Experimental protocols. Initially LA pressure was increased with
intravenous infusion of isotonic saline and decreased with IVC external compression. Both the infusions and compressions were performed in a sequential manner with data acquired at predetermined
increments and decrements of mean LA pressure. After achieving a
stable hemodynamic state at each LA pressure level, the LA and the
LV pressures and Doppler data were acquired. After a stable hemodynamic state was achieved, to evaluate the influence of LV relaxation
on Ea and its peak acceleration rate, dobutamine was administered at
a dose of 5 ␮g 䡠 kg⫺1 䡠 min⫺1 with Doppler and pressure data were
acquired. Dobutamine infusion was then terminated, and, after the
animals returned to their baseline state, esmolol with its negative
lusitropic properties was administered (0.5 mg/kg iv) with subsequent
reacquisition of data. To assess the possible interaction between atrial
pressure and ventricular relaxation on the peak acceleration rate of Ea,
fluid administration and IVC compression were repeated during dobutamine and esmolol infusion.
Study group. The institutional review board of Baylor College of
Medicine approved the protocol, and all patients provided written,
informed consent. The study sample comprised 190 consecutive
patients referred for echocardiographic evaluation at our laboratory.
Patients were divided according to the mitral inflow pattern, clinical
data, and echocardiographic examination into four groups [control,
impaired relaxation (IR), pseudonormal (PN), and restrictive (Res)].
Patients in the control group (n ⫽ 55) had no history or evidence of
cardiovascular disease with normal LV dimensions, wall thickness,
mass, normal PA systolic pressure, and no evidence of significant
valvular pathology on echocardiography. The IR group consisted of
41 patients with hypertension, coronary artery disease, and/or LV
hypertrophy and a mitral inflow pattern with an early to late transmitral flow velocity (E/A) ratio ⬍1.0. The PN group consisted of 46
patients with symptoms of pulmonary congestion and an E/A ratio
ⱖ1.0. The Res LV filling group consisted of 48 patients with symptoms of pulmonary congestion and an E/A ratio ⱖ2.0.
An additional group of 60 consecutive patients who were undergoing right heart catheterization in the cardiac catheterization laboratory (n ⫽ 25) or the intensive care unit (n ⫽ 35) was included. All
were in sinus rhythm (60 –100 beats/min) and with satisfactory Doppler and pressure recordings and no evidence of mitral stenosis,
prosthetic mitral valve, or severe mitral regurgitation. Patients had
simultaneous echocardiographic and hemodynamic measurements.
Echocardiographic studies. Patients were imaged in a supine position with an ultrasound system equipped with harmonic imaging, a
multifrequency transducer, and TDI capability. After acquisition of
parasternal and apical views, pulse-Doppler was utilized to record
transmitral and pulmonary venous flow in the apical four-chamber
view as previously described (8). TDI was applied in the PW mode to
record the mitral annular velocities at the septal and lateral areas.
Studies were recorded for later playback and analysis.
Echocardiographic analysis. The analysis was performed offline
without knowledge of hemodynamic data. LV ejection fraction and
LA maximum volume were performed per the recommendations of
the American Society of Echocardiography (12). All Doppler values
represent the average of three beats. Pulmonary artery (PA) systolic
pressure was estimated by using the tricuspid regurgitation jet. Mitral
inflow was analyzed for peak E, peak A velocities, E/A ratio, and
deceleration time of E velocity. From the pulmonary vein flow
velocities, the systolic filling fraction (SFF) and difference in atrial
velocity duration between pulmonary vein and mitral inflow (Ar-A)
duration were computed (5, 11). Ea and late diastolic mitral annulus
J Appl Physiol • VOL
RESULTS
Animal Studies
Hemodynamics and Doppler measurements. Table 1 summarizes the hemodynamic and TD data (average of the two
annular sites shown in the table because similar observations
were noted at each separate site) at the different experimental
stages. Volume expansion resulted in an increase in LV filling
pressures, annular Ea, and its peak and mean acceleration rate.
IVC occlusion resulted in significantly opposite changes in the
above measurements.
Dobutamine infusion resulted in shorter ␶ along with an
increase in annular Ea and its peak and mean acceleration rate.
Esmolol infusion resulted in significantly opposite changes in
the above measurements. In all of the above interventions, only
esmolol infusion resulted in a significant change in TEa-E,
prolonging it.
Relation of TD signals to LV hemodynamics. In individual
dogs, the correlation coefficient of Ea velocity and peak and
mean acceleration rate of Ea with LA mean pressure ranged
from 0.4 to 0.75 (P value range 0.1– 0.03). As for LV relaxation, peak Ea velocity (r ⫽ ⫺0.76), and its mean (r ⫽ ⫺0.73)
and peak acceleration rates (r ⫽ ⫺0.75) exhibited strong
relations to ␶ (all P ⬍ 0.001) and ⫺dP/dt (r ranging from 0.65
to 0.79, all P ⬍ 0.001) (Fig. 1). Peak and mean acceleration
rates of Ea were also significantly related to LV minimal
pressure (r ⫽ ⫺0.68 and r ⫽ ⫺0.65, respectively, both P ⬍
0.01).
The relation of peak acceleration rate of Ea to the transmitral
pressure gradient was evaluated in all the experimental stages
where ␶ was ⱖ50 ms and in those where ␶ was ⬍50 ms. There
was no significant relation between peak acceleration rate of Ea
100 • FEBRUARY 2006 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.32.246 on May 9, 2017
Human Studies
velocity by tissue Doppler (Aa) velocities at the two areas of the
mitral annulus were measured (septal and lateral). Peak and mean
acceleration rates of Ea at septal and lateral sides of mitral annulus
were also measured. In addition, the time interval between peak of R
wave and onset of mitral E velocity as well as the time interval
between peak of R wave and onset of Ea at the four areas of the mitral
annulus were measured (10).
Hemodynamic measurements. Hemodynamic data were collected
by an investigator unaware of the echocardiographic measurements, at
end expiration, and represent the average of five cycles. Mean wedge
pressure (PCWP; verified by fluoroscopy, phasic changes in pressure
waveforms, and oxygen saturation) was determined using balanced
transducers (0 level at midaxillary line).
Statistical analysis. Ea and its peak and mean acceleration rates
were correlated with hemodynamic parameters by regression analysis.
Stepwise regression was then used to determine the hemodynamic
parameters that correlated best with the individual Doppler variables.
The study was powered to detect a correlation coefficient of at least
0.4 between the transmitral pressure gradient and peak acceleration
rate of Ea (power ⫽ 80%, P ⫽ 0.05). Repeated-measures ANOVA
with Bonferroni correction was used to compare Doppler and hemodynamic parameters at the different lusitropic states (baseline, dobutamine, and esmolol) and loading conditions.
ANOVA with Bonferroni correction was used to compare the
control group with each of the other three groups (IR, PN, and Res).
Receiver operator characteristic curves were applied to examine the
accuracy of TDI signals in identifying patients with increased LV
filling pressures. Linear regression analysis was used to relate mean
wedge pressure to Doppler measurements. Significance was set at a P
value ⬍0.05.
681
LV DIASTOLIC FUNCTION AND ANNULAR ACCELERATION RATE
Table 1. Hemodynamics and TD velocities during volume loading, IVC occlusion, and dobutamine and esmolol infusions
Hemodynamic Parameter
Baseline
Volume Loading
IVC Occlusion
Dobutamine
Esmolol
LV stroke volume, ml
Heart rate, beats/min
LVEDP, mmHg
LA mean pressure, mmHg
␶, ms
LV ⫺dP/dt, mmHg/s
Ea, cm/s
Ea mean acceleration rate, cm/s2
Ea peak acceleration rate, cm/s2
TEa-E, ms
20⫾5a
115⫾6
5⫾3a
7⫾4a
42⫾10
1,840⫾365a
5.2⫾1a
74⫾15a
105⫾25a
1⫾5
28⫾4c
115⫾8
11⫾5b
11⫾6.4b
44⫾9
1,925⫾400b
5.9⫾1.2b
90⫾19b
129⫾21b
0⫾5
14⫾4
118⫾12
2.1⫾0.6f
3⫾2f
39⫾8
1,420⫾400d
4.5⫾1d
63⫾20d
91⫾19d
1⫾3
23⫾4.5f
136⫾3g
2.6⫾0.8f
3.5⫾2.2f
26⫾7g
3,720⫾420f
8.8⫾0.8f
100⫾21f
143⫾33f
0⫾3
16⫾5.4
103⫾8e
14.5⫾3
15⫾4
87⫾8e
725⫾367
3⫾0.7
53⫾20
69⫾18
23⫾4h
Values are means ⫾ SD. TD, tissue Doppler; IVC, inferior vena cava; LV, left ventricular; LVEDP, LV end-diastolic pressure; LA, left atrial; ␶, time constant
of LV relaxation; LV dP/dt, first derivative of LV pressure in diastole; Ea, early diastolic annular velocity; TEa-E, Ea-E time interval. a P ⬍ 0.05 vs. volume
loading, IVC occlusion, dobutamine, and esmolol stages; b P ⬍ 0.05 vs. IVC occlusion, dobutamine and esmolol stages; c P ⬍ 0.05 vs. IVC occlusion and esmolol
stages; d P ⬍ 0.05 vs. dobutamine and esmolol stages; e P ⬍ 0.05 vs. baseline, volume loading, and IVC occlusion stages; f P ⬍ 0.05 vs. esmolol stage; g P ⬍
0.05 vs. baseline, volume infusion, IVC occlusion, and esmolol; h P ⬍ 0.05 vs. baseline, volume loading, IVC occlusion, and dobutamine stages.
Human Studies
Clinical characteristics and Doppler echocardiographic variables for the 190 patients, divided into four groups, are listed
in Table 2. No significant differences were observed between
the four groups in age, heart rate, or blood pressure. The
control, PN, and Res groups displayed a higher E velocity, E/A
ratio, and a shorter deceleration time compared with the IR
group. Mitral inflow, however, did not differentiate between
normal and PN groups. However, as previously reported, LA
volume, PA systolic pressure, pulmonary venous SFF, and
Ar-A duration were useful in that regard (see Table 2).
As expected, septal and lateral Ea velocities were significantly lower in patients with PN and restrictive LV filling
compared with controls, whereas TEa-E was significantly longer
in the patient groups (Table 2).
Similar to peak Ea velocity, peak and mean acceleration rate
of Ea were significantly lower in patients with PN and Res LV
filling compared with controls (ANOVA, P ⬍ 0.001; Bonfer-
Fig. 1. Relation of time constant of LV relaxation (␶) vs. septal peak early
diastolic annular (Ea) velocity (left) and its peak acceleration rate (right).
J Appl Physiol • VOL
roni t-test P ⬍ 0.05 for control group vs. each of the other three
groups). Figure 3 illustrates examples of TDI signals in four
representative cases. Table 3 summarizes the accuracy of peak
Ea velocity and its acceleration rate in identifying patients with
impaired LV relaxation despite elevated filling pressures (ROC
curves shown in Fig. 4).
Relation to mean PCWP. The mean age of this group was
60 ⫾ 15 yr. The mean arterial pressure was 81 ⫾ 15 mmHg,
whereas the mean PA pressure was 33 ⫾ 10 mmHg. Mitral
inflow pattern was that of IR in 20 patients, PN filling in 25
patients, and restrictive filling in 15 patients. Mean PCWP was
20 ⫾ 10 (range 5– 45) mmHg. A nonsignificant trend for an
inverse relation was noted between mean PCWP and septal
(and lateral) peak acceleration rate (peak acceleration rate: r ⫽
⫺0.23, P ⫽ 0.08, Fig. 5). However, significant correlations
were noted with mitral E/A ratio (r ⫽ 0.5, P ⬍ 0.05), E/Ea
Fig. 2. Relation of peak acceleration rate of Ea vs. transmitral pressure
gradient. Solid line and F, stages where ␶ was ⬍50 ms; dashed line and E,
stages where ␶ was ⱖ50 ms. In the presence of normal or enhanced relaxation,
a direct significant relation was present (r ⫽ 0.71, P ⬍ 0.01), whereas with
impaired relaxation, no relation was observed between peak acceleration rate
of Ea and transmitral pressure gradient (P ⬎ 0.3).
100 • FEBRUARY 2006 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.32.246 on May 9, 2017
and the pressure gradient in the stages where ␶ ⱖ 50 ms,
whereas a significant positive relation emerged in the stages
where ␶ was ⬍50 ms (Fig. 2).
On multiple regression analysis (model R2 ⫽ 0.79, P ⬍ 0.01),
the predictors of peak acceleration rate of Ea velocity were ␶,
LV minimal pressure, and transmitral pressure gradient.
682
LV DIASTOLIC FUNCTION AND ANNULAR ACCELERATION RATE
Table 2. Clinical and Doppler findings in the 4 patient groups
Age, yr
Heart rate, min⫺1
Mean arterial pressure, mmHg
LV EF, %
Left atrial volume, ml
PA systolic pressure, mmHg
Mitral E/A ratio
Deceleration time, ms
Pulmonary veins, SFF
Ar-A duration, ms
Septal Ea, cm/s
Septal mean acceleration rate, cm/s2
Septal peak acceleration rate, cm/s2
Lateral Ea, cm/s
Lateral mean acceleration rate, cm/s2
Lateral peak acceleration rate, cm/s2
TEa-E, ms
Control
(n ⫽ 55)
IR
(n ⫽ 41)
PN
(n ⫽ 46)
Res
(n ⫽ 48)
61⫾15
73⫾12
90⫾14
65⫾3a
43⫾11a
30⫾3d
1.1⫾0.1
220⫾86e
0.6⫾0.1d
0⫾8a
9.3⫾3.2a
131⫾53a
259⫾99a
11.3⫾4.7a
161⫾68a
311⫾116a
3⫾5a
62⫾15
75⫾13
97⫾19
53⫾17
73⫾28c,e
35⫾13e
0.7⫾0.16c
252⫾84d
0.59⫾0.1d
18⫾10d
5.2⫾2.1
77⫾41
159⫾88
7.5⫾2.5
98⫾38
185⫾79
29⫾5
61⫾15
75⫾13
94⫾16
55⫾17
81⫾26
44⫾10.5
1.4⫾0.29
188⫾69
0.52⫾0.1e
45⫾11e
5.5⫾2.3
84⫾43
178⫾87
6.9⫾2.7
134⫾49
210⫾105
33⫾3
67⫾12
70⫾13
87⫾19
50⫾15
89⫾22
48⫾10
3⫾0.9b
169⫾43
0.42⫾0.1
58⫾10
4.7⫾1.5
74⫾32
149⫾75
7.4⫾3.2
100⫾48
193⫾112
40⫾3
ratio (r ⫽ 0.69, P ⬍ 0.01), isovolumic relaxation time (r ⫽
⫺0.55, P ⬍ 0.01), and SFF (r ⫽ ⫺0.53, P ⬍ 0.05).
DISCUSSION
The animal experiments show that the hemodynamic determinants of peak acceleration rate of Ea are transmitral pressure
gradient, LV minimal pressure, and LV relaxation. The relation
between peak acceleration rate of Ea and transmitral pressure
gradient is a direct linear relation only in the presence of
normal or enhanced LV relaxation, but no direct correlation
was noted in the presence of impaired LV relaxation. The
clinical studies confirm and extend these animal observations.
The peak acceleration rate of Ea, at either side of the mitral
annulus, in patients with impaired LV relaxation (IR, PN, and
Res groups) was significantly lower than in the age-matched
control group. Overall its accuracy in identifying patients with
impaired relaxation and elevated filling pressures was similar
to peak Ea velocity. Furthermore, in the subgroup with simul-
Fig. 3. Examples of mitral inflow and tissue Doppler imaging (TDI) at septal annulus from patients in each of the 4 groups. Note the reduced Ea velocity in
patients with pseudonormal (PN) and restrictive (Res.) left ventricular (LV) filling, despite increased LV filling pressures. Peak acceleration rate of Ea in the
normal subject (NL) was 330 cm/s2, whereas it was reduced to 140 cm/s2 in the patient with impaired relaxation (IR) pattern, to 138 cm/s2 in the patient with
PN pattern, and to 160 cm/s2 in the patient with Res filling.
J Appl Physiol • VOL
100 • FEBRUARY 2006 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.32.246 on May 9, 2017
Values are means ⫾ SD. a P ⬍ 0.05 vs. impaired relaxation (IR), pseudonormal (PN), and restrictive filling (Res) groups; b P ⬍ 0.05 vs. control, IR, and PN,
groups; c P ⬍ 0.05 vs. control and PN groups; d P ⬍ 0.05 vs. PN and Res groups; e P ⬍ 0.05 vs. Res group. Ar-A, difference in atrial velocity duration between
pulmonary vein and mitral inflow.
LV DIASTOLIC FUNCTION AND ANNULAR ACCELERATION RATE
Table 3. Accuracy of peak Ea velocity and acceleration rate
of Ea in identifying patients with impaired LV relaxation
despite elevated filling pressures
Septal Ea (⬍5.6 cm/s)
Septal peak acceleration rate
(⬍195.5 cm/s2)
Lateral Ea (⬍8.6 cm/s)
Lateral peak acceleration rate
(⬍252 cm/s2)
Sensitivity,
%
Specificity,
%
Area under ROC curve
66
88
0.875 (0.81–0.94)*
76
79
75
75
0.78 (0.7–0.86)*
0.82 (0.75–0.9)*
74
72
0.78 (0.71–0.86)*
*P ⬍ 0.001; numbers between parenthesis refer to 5–95% confidence
intervals. ROC, receiver operator characteristics.
taneous invasive measurements, no relation was noted between
mean PCWP and peak acceleration rate of Ea.
Animal Studies
Fig. 4. Receiver operator characteristics (ROC) curves showing the accuracy
of septal peak (Pk) acceleration (Acc) rate of Ea (left) and lateral peak
acceleration rate of Ea (right) in identifying patients with impaired LV
relaxation despite increased LV filling pressures (PN and Res filling groups).
J Appl Physiol • VOL
The relation between the peak acceleration rate of Ea and
filling pressures is a complicated one and overall very similar
to that of the peak Ea velocity itself, as previously reported in
animal (3, 7) and human studies (1, 2). The relation between
LA pressure and peak acceleration rate of Ea in the presence of
cardiac dysfunction is very important for the clinical application of Ea acceleration rate in the clinical setting, because the
assessment of LV filling pressures is frequently needed in
patients with cardiac disease. The previous animal work was
limited in that regard owing to the occurrence of only small
changes in LA pressure with beta-blockers. However, the peak
acceleration rate of Ea can be used to predict LV filling
pressures in normal subjects, given the direct relation between
this Doppler measurement and preload in normal states.
On the other hand, our animal study provides the pathophysiological reasons for not applying the peak acceleration rate of
Ea to the estimation of LV filling pressures, in the presence of
impaired LV relaxation (Fig. 2). Similar to the acceleration rate
of Ea, TEa-E duration was altered by esmolol, but, unlike the
acceleration rate, IVC occlusion and volume infusion had no
significant effect on this time interval. Overall these results are
similar with the observations of Hasegawa et al. (3), who noted
that Ea was progressively delayed after LA to LV pressure
crossover and was significantly related to ␶ in an animal model
of pacing-induced heart failure.
Human Studies
In the human studies, the mean and peak acceleration rate of
Ea at either side of the mitral annulus were significantly lower
in patients with impaired LV relaxation, irrespective of LV
filling pressures. It is interesting that the relation between mean
wedge pressure and peak acceleration rate of Ea, shown in Fig.
5, in patients with cardiac disease was very similar to that
observed in the canine experiments between transmitral pressure gradient and peak acceleration rate of Ea when LV
relaxation was impaired as shown in Fig. 2 (dashed line and
open circles).
Our study also shows that the accuracy of peak acceleration
rate of Ea at either side of the mitral annulus for identifying
patients with impaired LV relaxation despite elevated filling
pressures (PN and Res groups) is similar to that of the peak Ea
Fig. 5. Plot of mean wedge pressure (PCWP) vs. septal Ea peak acceleration
rate.
100 • FEBRUARY 2006 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.32.246 on May 9, 2017
We used the PW signal at each side of the mitral annulus to
calculate the peak acceleration rate of Ea. PW, unlike color
Doppler, has the major advantage of superior temporal resolution, which suits well the need to calculate the peak acceleration rate given the very short time (frequently ⬍50 ms) when
acceleration of Ea is occurring. An additional advantage to our
method lies in the higher sampling rate afforded by using 20
intervals for deriving the peak acceleration rate, making it
much less likely to miss the highest acceleration rate when
limiting the analysis to longer time intervals.
In the previous study (4), the peak acceleration rate of the Ea
velocity, particularly at the septal side of the mitral annulus,
increased significantly with blood infusion but was not altered
by dobutamine or metoprolol administration. Unlike these
findings, we noted that changes in the myocardial lusitropic
state with either dobutamine or esmolol were effective in
producing significant changes in peak acceleration rate of Ea.
The magnitude of change in Ea peak acceleration rate was
comparable to the change in peak Ea velocity induced by these
drugs. Furthermore, the peak acceleration rate of Ea had a
significant inverse correlation with the invasive measurements
of LV relaxation that was almost identical to those of Ea peak
velocity.
683
684
LV DIASTOLIC FUNCTION AND ANNULAR ACCELERATION RATE
velocity. There was no incremental information gained over
peak Ea velocity by measuring its acceleration rate. Given the
above findings and the complexity of measurement of acceleration rate, peak Ea velocity rather than its acceleration rate is
more suitable for the daily application in the laboratory.
REFERENCES
J Appl Physiol • VOL
100 • FEBRUARY 2006 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.32.246 on May 9, 2017
1. Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L,
Morehead AJ, Zuckerman J, and Thomas JD. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy
volunteers. J Am Coll Cardiol 36: 1664 –1669, 2000.
2. Graham RJ, Gelman JS, Donelan L, Mottram PM, and Peverill RE.
Effect of preload reduction by haemodialysis on new indices of diastolic
function. Clin Sci (Lond) 105: 499 –506, 2003.
3. Hasegawa H, Little WC, Ohno M, Brucks S, Morimoto A, Cheng HJ,
and Cheng CP. Diastolic mitral annular velocity during the development
of heart failure. J Am Coll Cardiol 41: 1590 –1597, 2003.
4. Hashimoto I, Bhat AH, Li X, Jones M, Davies CH, Swanson JC,
Schindera ST, and Sahn DJ. Tissue Doppler-derived myocardial acceleration for evaluation of left ventricular diastolic function. J Am Coll
Cardiol 44: 1459 –1466, 2004.
5. Kuecherer HF, Muhiudeen IA, Kusumoto FM, Lee E, Moulinier LE,
Cahalan MK, and Schiller NB. Estimation of mean left atrial pressure
from transesophageal pulsed Doppler echocardiography of pulmonary
venous flow. Circulation 82: 1127–1139, 1990.
6. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, and Quinones
MA. Doppler tissue imaging: a noninvasive technique for evaluation of
left ventricular relaxation and estimation of filling pressures. J Am Coll
Cardiol 30: 1527–1533, 1997.
7. Nagueh SF, Sun H, Kopelen HA, Middleton KJ, and Khoury DS.
Hemodynamic determinants of the mitral annulus diastolic velocities by
tissue Doppler. J Am Coll Cardiol 37: 278 –285, 2001.
8. Nishimura RA and Tajik AJ. Evaluation of diastolic filling of left
ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta Stone. J Am Coll Cardiol 30: 8 –18, 1997.
9. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield
MM, and Tajik AJ. Clinical utility of Doppler echocardiography and
tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 102: 1788 –1794, 2000.
10. Rivas-Gotz C, Khoury DS, Manolios M, Rao L, Kopelen HA, and
Nagueh SF. Time interval between onset of mitral inflow and onset of
early diastolic velocity by tissue Doppler: a novel index of left ventricular
relaxation: experimental studies and clinical application. J Am Coll Cardiol 42: 1463–1470, 2003.
11. Rossvoll O and Hatle LK. Pulmonary venous flow velocities recorded by
transthoracic Doppler ultrasound: relation to left ventricular diastolic
pressures. J Am Coll Cardiol 21: 1687–1696, 1993.
12. Schiller NB, Shah PM, Crawford MH, DeMaria A, Devereux R,
Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, et al.
Recommendations for quantitation of the left ventricle by twodimensional echocardiography: American Society of Echocardiography Committee on Standards, Subcommittee on quantitation of twodimensional echocardiograms. J Am Soc Echocardiogr 2: 358 –367,
1989.
13. Weiss JL, Frederiksen JW, and Weisfeldt ML. Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin
Invest 58: 751–760, 1976.
14. Zile MR and Brutsaert DL. New concepts in diastolic dysfunction and
diastolic heart failure: Part I. Diagnosis, prognosis, and measurements of
diastolic function. Circulation 105: 1387–1393, 2002.