LEFT ATRIAL AND VENTRICULAR MECHANICS
Impact of Diastolic Dysfunction Grade on Left Atrial
Mechanics Assessed by Two-Dimensional Speckle
Tracking Echocardiography
Kyoko Otani, MD, Masaaki Takeuchi, MD, Kyoko Kaku, MD, Nobuhiko Haruki, MD, Hidetoshi Yoshitani, MD,
Masahito Tamura, MD, Haruhiko Abe, MD, Masahiro Okazaki, MD, Toshiyuki Ota, MD, Roberto M. Lang, MD,
and Yutaka Otsuji, MD, Kitakyushu, Japan; Chicago, Illinois
Background: Mitral inflow patterns reflect not only left ventricular diastolic function but also left atrial (LA)
remodeling. The aim of this study was to determine the effects of left ventricular diastolic dysfunction on LA
volumetric and functional parameters assessed using two-dimensional speckle-tracking echocardiography.
Methods: Two-dimensional speckle-tracking analysis of the LA wall in the apical four-chamber view was
performed in 268 subjects. Subjects were classified according to diastolic dysfunction grade. Indexed
maximum and minimum LA volumes and indexed LA volume before atrial contraction were measured from
LA volume waveforms. Expansion, passive emptying, and active emptying indices were calculated.
Results: LA volumes increased progressively with advanced stages of diastolic dysfunction. The expansion
index and passive emptying index showed progressive decreases according to the grade of diastolic dysfunc-
tion. The active emptying index increased until mild diastolic dysfunction and thereafter progressively
decreased until reaching severe diastolic dysfunction. Significant correlations were noted between the active
emptying index and A-wave velocity (r = 0.31, P < .01) and between the E/E0 ratio and the expansion index
(r = 0.56, P < .01).
Conclusions: LA volumes and functional parameters derived from two-dimensional speckle-tracking echocar-
diography vary according to the level of diastolic dysfunction. These results suggest that left ventricular
diastolic dysfunction also predicts the severity of LA remodeling. (J Am Soc Echocardiogr 2010;23:961-7.)
Keywords: Left atrium, Diastolic dysfunction, Speckle-tracking echocardiography
Left ventricular (LV) diastolic function is frequently assessed using Several studies have reported that LA volumes and function reflect
Doppler mitral inflow velocity patterns. In the earlier stages of LV the severity of diastolic dysfunction.7-12 Two-dimensional (2D)
diastolic dysfunction, the E-wave velocity is low because of delayed speckle-tracking echocardiography (2DSTE) is a new modality that
LV pressure decay. As LV filling pressure becomes elevated in the is capable of measuring phasic changes in LA volumes and strain.13,14
more advanced stages of LV diastolic dysfunction, left atrial (LA) We have previously reported the feasibility and accuracy of measuring
pressure rises to maintain adequate LV filling, and subsequently, the LA volumes using 2DSTE when assessing the effect of aging on LA
E-wave velocity becomes higher than the A-wave velocity. function in healthy subjects.15 However, the effects of LV diastolic
Sustained elevated LA pressure results in LA remodeling, which is dysfunction on LA volumetric and functional indices derived from
characterized by LA dilatation and impaired LA functional parame- LA volume curves using 2DSTE have not been systematically studied.
ters.1-6 Accordingly, the mitral inflow patterns reflect not only LV Accordingly, in this study, we sought to determine the effects of LV
diastolic function but also LA remodeling. diastolic dysfunction grade on LA volumes and function assessed
by 2DSTE.
From the Second Department of Internal Medicine (K.O., M.T., K.K., N.H., H.Y.,
M.T., H.A., M.O., Y.O.) and the Department of Laboratory and Transfusion METHODS
Medicine (T.O.), University of Occupational and Environmental Health, School of
Medicine, Kitakyushu, Japan; and the Non-Invasive Cardiac Imaging Study Subjects
Laboratory, University of Chicago Medical Center, Chicago, Illinois (R.M.L.). The study group consisted of 268 subjects in normal sinus rhythm
Reprint requests: Masaaki Takeuchi, MD, Second Department of Internal Medi- (mean age, 64 6 12 years; 171 men), including 85 healthy subjects
cine, University of Occupational and Environmental Health, School of Medicine, who were recruited from hospital employees and their relatives. All
1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan (E-mail: takeuchi@ healthy subjects were aged > 40 years and did not have histories of
med.uoeh-u.ac.jp). hypertension, diabetes, and/or cardiovascular disease. None of the
0894-7317/$36.00 subjects were taking cardiac medications. In addition, 183 consecu-
Copyright 2010 by the American Society of Echocardiography. tive patients, who were referred for clinically indicated transthoracic
doi:10.1016/j.echo.2010.06.023 echocardiography (iE33; Philips Medical Systems, Andover, MA),
961
962 Otani et al Journal of the American Society of Echocardiography
September 2010
Abbreviations
were studied. Exclusion criteria speckle-tracking analysis in nine regions throughout the cardiac cycle.
included inadequate image Manual adjustments of the LA tracking points were performed when
LA = Left atrial quality of the LA wall, presence required. LA volumes were calculated using the single-plane area-
LAVImax = Maximal indexed of cardiac arrhythmias, mitral length formula. Computer-generated LA volume curves throughout
left atrial volume valvular disease, and rapid heart the cardiac cycle were obtained, from which maximal and minimal
rates (usually >90 beats/min) LA volumes and LA volume before atrial contraction were measured.
LAVImin = Minimal indexed resulting in fusion of the E and These values were indexed to body surface area (LAVImax, LAVImin,
left atrial volume
A waves. The institutional review and LAVIpre-a, respectively).
LAVIpre-a = Indexed left board of the hospital approved Thereafter, the following LA emptying volume indices were
atrial volume before atrial the study, and all subjects calculated9,10,18,19:
contraction provided written informed
consent before participation. 1. LA total emptying volume index = LAVImax LAVImin,
LV = Left ventricular 2. LA passive emptying volume index = LAVImax LAVIpre-a, and
2D = Two-dimensional 3. LA active emptying volume index = LAVIpre-a LAVImin.
Echocardiography
2DSTE = Two-dimensional Two-dimensional echocardio- LA reservoir function was assessed using two indices:
speckle-tracking
graphic examinations were 1. expansion index = [(LAVImax LAVImin)/LAVImin] 100, and
echocardiography
performed using a broadband 2. diastolic emptying index = [(LAVImax LAVImin)/LAVImax]
transducer connected to a commercially available ultrasound 100.
machine (S5-1 probe, iE33). From the apical four-chamber and
two-chamber views, LV end-diastolic and end-systolic volumes and LA conduit function was assessed using two indices:
ejection fraction were calculated using the biplane Simpson’s
method.16 Each subject underwent pulsed-wave Doppler examina- 1. passive emptying percentage of total emptying = [(LAVImax
tion of mitral inflow obtained in the apical four-chamber view before LAVIpre-a)/(LAVImax LAVImin)] 100, and
and during the Valsalva maneuver. Pulmonary venous flow was also 2. passive emptying index = (LAVImax LAVIpre-a)/LAVImax
obtained. Doppler tissue imaging, used to measure septal mitral 100.
annular velocity, was performed by placing the sample volume in Booster pump function was assessed using two indices:
the septal corner of the mitral annulus in the apical four-chamber
view. LV outflow tract velocities were obtained from the apical 1. active emptying percentage of total emptying = [(LAVIpre-a
long-axis view. Isovolumic relaxation time was calculated as the LAVImin)/(LAVImax LAVImin)] 100, and
time interval between aortic valve closure and mitral valve opening 2. active emptying index = (LAVIpre-a LAVImin)/LAVIpre-a
using mitral inflow and LV outflow tract velocities. 100.
Assessment of LV Diastolic Function Grade Statistical Analysis
From mitral inflow velocities, the E-wave and A-wave velocities, Continuous data are expressed as mean 6 SD. In each subject, data
E-wave deceleration time, and E/A velocity ratio were measured. points describing LA volume according to time were exported to
Peak diastolic annular velocity during early diastolic rapid filling (E0 ) spreadsheet software (Microsoft Excel; Microsoft Corporation,
was also measured to calculate the E/E0 ratio in all subjects. All Redmond, WA) to calculate LA volume waveforms. To adjust for in-
Doppler measurements were averaged from three consecutive beats. tersubject differences in heart rate, time sequences were normalized
LV diastolic function was categorized as normal, mild (defined as to the percentage of systolic duration (i.e., at end-systole, t was 100%)
impaired relaxation without evidence of increased filling pressures), as well as diastolic duration (i.e., at end-diastole, t was 100%). Data
moderate (defined as impaired relaxation associated with moderate were analyzed using analysis of variance with post hoc analysis of
elevation of filling pressures or pseudonormal filling), or severe Bonferroni’s correction between diastolic dysfunction grade groups.
(defined as advanced reduction in compliance or reversible or Also, linear or polynomial regression analysis was performed to
fixed restrictive filling), as previously described by Redfield et al.17 determine LA functional indices and traditional diastolic parameters.
(Table 1). Subjects were required to meet at least two Doppler criteria A P value < .05 was considered significant. Intraobserver and interob-
consistent with mild, moderate, or severe diastolic dysfunction to be server variability for the LA volume measurements using 2DSTE
so classified. Subjects with one criterion for diastolic dysfunction or (8%-13% and 9%-14%, respectively) were reported in our previous
those whose parameters were borderline and suggestive of but not study.15
definitive of diastolic dysfunction were classified as indeterminate.
Assessment of LA Volume Curve Versus Time Using 2DSTE RESULTS
Three consecutive beats were acquired in the apical four-chamber
view (frame rate, 61 6 14 frames/sec) using second harmonic mode. Clinical characteristics and standard echocardiographic findings are
Two-dimensional endocardial tracking of the LA wall was performed shown in Table 2. Diastolic function was classified as normal or abnor-
using speckle-tracking software (QLAB version 7.0, TMQ; Philips mal in 208 subjects (78%) and as indeterminate in 60 participants
Medical Systems).15 Initialization of the end-diastolic frame was (22%). Among the 60 with indeterminate diastolic dysfunction, 53
completed with three points (septal and lateral corner of the mitral had E/A ratios < 0.75 but E/E0 ratios > 10. Among the 183 patients,
annulus and the roof of the left atrium). The software provides six the clinical diagnoses included ischemic heart disease (n = 72), hyper-
tracking regions of interest on the LA wall and automatically performs tensive heart disease (n = 29), hypertrophic cardiomyopathy (n = 9),
Journal of the American Society of Echocardiography Otani et al 963
Volume 23 Number 9
Table 1 Doppler criteria for classification of diastolic function
Normal diastolic Mild diastolic Moderate diastolic Severe diastolic
function dysfunction dysfunction dysfunction
Mitral inflow 0.75 < E/A < 1.5, E/A # 0.75 0.75 < E/A < 1.5, E/A > 1.5,
DcT > 140 msec DcT > 140 msec DcT < 140 msec
Mitral inflow at peak DE/A < 0.5 DE/A < 0.5 DE/A $ 0.5
Valsalva maneuver
Doppler tissue imaging of E/E0 < 10 E/E0 < 10 E/E0 $ 10 E/E0 $ 10
mitral annular motion
Pulmonary venous flow S $ D, ARdur < Adur S > D, ARdur < Adur S < D or ARdur S < D or ARdur
> Adur + 30 msec > Adur + 30 msec
A, Velocity at atrial contraction, Adur, A duration; ARdur, pulmonary venous atrial reversal flow duration; D, diastolic forward flow, DcT, deceleration
time of the E-wave velocity; E, peak early filling velocity; E0 , peak diastolic annular velocity during early diastolic filling at the septal corner; S, sys-
tolic forward flow.
Table 2 Clinical characteristics and echocardiographic findings in all subjects
Normal Mild Moderate Severe
Variable (n = 77) (n = 30) (n = 71) (n = 30) P (ANOVA)
Age (y) 57 6 10 67 6 10 69 6 11 64 6 13 <.001
Men/women 46/31 16/14 52/19 23/7
HR (beats/min) 63 6 8 68 6 10 63 6 11 72 6 12 <.001
SBP (mm Hg) 127 6 14 139 6 22 141 6 26 133 6 32 <.05
DBP (mm Hg) 78 6 11 81 6 12 77 6 14 78 6 21 NS
IVRT (msec) 75 6 24 107 6 34 108 6 32 79 6 31 <.001
E velocity (cm/sec) 71 6 13 49 6 12 87 6 25 103 6 18 <.001
A velocity (cm/sec) 63 6 14 77 6 15 89 6 29 43 6 12 <.001
E/A ratio 1.2 6 0.2 0.6 6 0.1 1.1 6 0.2 2.5 6 0.7 <.001
DcT (msec) 195 6 37 263 6 80 226 6 63 124 6 13 <.001
E0 (cm/sec) 8.1 6 1.6 6.0 6 1.7 4.7 6 1.2 4.7 6 1.3 <.001
A0 (cm/sec) 9.5 6 1.7 9.1 6 1.7 7.4 6 1.9 5.1 6 1.6 <.001
E/E0 ratio (cm/sec) 8.9 6 1.6 8.3 6 1.1 20.0 6 8.1 23.5 6 8.1 <.001
LVEDVI (mL/m2) 54 6 13 56 6 26 85 6 35 102 6 36 <.001
LVESVI (mL/m2) 22 6 8 28 6 26 49 6 32 74 6 37 <.001
LVEF (%) 60 6 7 55 6 15 46 6 15 31 6 16 <.001
ANOVA, Analysis of variance; DBP, diastolic blood pressure; DcT, deceleration time of the E-wave velocity; E0 , peak diastolic annular velocity dur-
ing early diastolic filling at the septal corner; HR, heart rate; IVRT, isovolumic relaxation time; LVEDVI, LV end-diastolic volume index; LVESVI, LV
end-systolic volume index; LVEF, LV ejection fraction; SBP, systolic blood pressure.
dilated cardiomyopathy (n = 18), aortic valve disease (n = 20), and Although LAVImax, LAVImin, and LAVIpre-a were increased signifi-
a variety of other cardiac abnormalities (n = 35). cantly in parallel with the severity of diastolic dysfunction, the
The isovolumic relaxation time was prolonged from normal in magnitude of increase in LAVImin was greater that the increase in
patients with mild diastolic dysfunction but did not show progressive LAVImax with worsening diastolic dysfunction. The passive emptying
prolongation as the severity of diastolic dysfunction increased to volume index was significantly lower in the mild diastolic dysfunction
moderate and severe. The E/E0 ratio increased with the severity of group compared with the normal diastolic function group. The active
diastolic dysfunction. LV volumes also increased with the severity emptying volume index increased until moderate diastolic dysfunc-
of diastolic dysfunction, whereas LV ejection fraction progressively tion and then declined with severe diastolic dysfunction.
decreased. The expansion and diastolic emptying indices were progressively
Adequate speckle tracking of the LA wall was obtained in all shorter as diastolic dysfunction increased from mild to severe. The
subjects. Figure 1 depicts LA volume curves acquired during one passive emptying index was also reduced in the most advanced stages
cardiac cycle in two representative patients with different grades of of diastolic dysfunction. The active emptying index was increased up
diastolic dysfunction. Figure 2 depicts average LA volume waveforms to mild diastolic dysfunction and then subsequently decreased until
for each grade of diastolic dysfunction severity. In addition to the LA severe diastolic dysfunction. A good linear correlation was noted
volumes, the contribution of passive filling and atrial contraction in between the active emptying index and A0 (r = 0.62, P < .01), and
each group can be appreciated. Table 3 depicts the LA volumes a weak but significant linear correlation was noted between the ac-
and the respective LA parameters obtained from LA volume curves tive emptying index and A-wave velocity (r = 0.31, P < .01). E0
among the four groups of normal or abnormal diastolic dysfunction. had a significant linear correlation with the passive emptying index
964 Otani et al Journal of the American Society of Echocardiography
September 2010
Figure 1 Two-dimensional speckle tracking on the LA wall and generated LA volume curves in two representative patients with
different diastolic dysfunction grades. (Left) A 60-year-old man with mild diastolic dysfunction and ischemic heart disease (LV ejection
fraction, 38%; E/E0 ratio, 9.8). (Right) A 60-year-old man with ischemic cardiomyopathy (LV ejection fraction, 21%; E/E0 ratio, 34) and
severe diastolic dysfunction.
Figure 2 Averaged LA volume waveforms in each group of diastolic dysfunction. The x axis denotes time during one cardiac cycle. To
adjust differences in heart rate, time sequences were normalized to the percentage of systolic duration as well as diastolic duration.
(Left) The y axis denotes the percentage change of LA volumes against maximal LA volume minus minimal LA volume in each group.
(Right) The y axis represents absolute LA volume change during one cardiac cycle in each group. The relative contribution of passive
filling and atrial contraction in each group is easily appreciated. AVC, Aortic valve closure.
(r = 0.63, P < .01), and E/E0 had significant polynomial correlations function; (2) LAVImin increased to a greater degree than LAVImax
with the expansion index (r = 0.56, P < .01) and passive emptying with worsening diastolic function; and (3) secondary calculation of
index (r = 0.53, P < .01). LA function using volumetric measures suggested that total emptying
To exclude the effects of LV systolic dysfunction on LA volume and fraction as well as the expansion index (measures of reservoir
function, subgroup analysis for subjects who had normal LV ejection function) decreased with worsening diastolic function. Thus, LA
fractions (>50%) was performed (n = 134). Similar results were remodeling maintains filling volumes in patients with mild or moder-
obtained in these groups compared with all subjects (Table 4). ate diastolic dysfunction, but this compensatory mechanism no longer
operates adequately in patients with severe LV diastolic dysfunction,
resulting in a reduction of LV filling volumes.
DISCUSSION
The results of this study demonstrate that LA volumes and function Normal Aging and LA Mechanical Properties
indices assessed using 2DSTE vary significantly according to the Using LA volume waveforms analysis derived from 2DSTE, we
severity of LV diastolic dysfunction. Specifically, (1) LAVImax, previously demonstrated the presence of age-related changes in LA
LAVImin, and LAVIpre-a all increased with worsening diastolic mechanical properties characterized by a progressive decline in
Journal of the American Society of Echocardiography Otani et al 965
Volume 23 Number 9
Table 3 LA volumes and LA functional parameters among diastolic dysfunction grade
Normal Mild Moderate Severe
Variable (n = 77) (n = 30) (n = 71) (n = 30) P (ANOVA)
2
LAVImax (mL/m ) 27.0 6 7.6 27.3 6 7.7 52.4 6 17.4 66.3 6 22.8 <.001
LAVImin (mL/m2) 14.4 6 4.5 16.1 6 5.3 36.5 6 14.8 54.0 6 19.6 <.001
LAVIpre-a (mL/m2) 19.5 6 5.7 22.2 6 6.7 44.2 6 15.6 58.7 6 20.2 <.001
TEVI (mL/m2) 12.7 6 3.9 11.2 6 3.8 15.9 6 6.0 12.4 6 5.0 <.001
PEI (mL/m2) 7.5 6 2.9 5.2 6 2.6 8.2 6 4.2 7.6 6 4.9 <.005
AEI (mL/m2) 5.1 6 1.8 6.1 6 2.2 7.6 6 3.2 4.8 6 2.2 <.001
Expansion index (%) 91.0 6 25.7 74.5 6 25.2 49.4 6 23.8 24.5 6 11.2 <.001
Diastolic emptying index 46.8 6 6.7 41.6 6 8.1 31.5 6 10.1 19.1 6 6.7 <.001
PE (%) 58.6 6 9.8 45.3 6 13.4 51.2 6 13.4 58.2 6 20.8 <.001
PEI (%) 27.6 6 7.0 19.3 6 7.9 16.1 6 6.6 11.3 6 6.0 <.001
AE (%) 41.4 6 9.8 54.7 6 13.4 48.8 6 13.4 41.8 6 20.8 <.001
AEI (%) 19.1 6 4.5 22.3 6 5.3 15.4 6 6.0 7.8 6 4.4 <.001
AE, Active emptying percentage of total emptying; AEI (mL/m2), active emptying volume index; AEI (%), active emptying index; ANOVA, analysis of
variance; PE, passive emptying percentage of total emptying; PEI (mL/m2), passive emptying volume index; PEI (%), passive emptying index; TEVI,
total emptying volume index.
Table 4 Parameters of LA function in normal LV ejection fraction group
Normal Mild Moderate Severe
Variable (n = 71) (n = 23) (n = 33) (n = 7) P (ANOVA)
LAVImax (mL/m2) 26.6 6 7.3 27.2 6 8.2 49.7 6 15.1 75.3 6 34.4 <.001
LAVImin (mL/m2) 14.2 6 4.3 15.6 6 5.2 31.8 6 12.2 61.2 6 28.5 <.001
LAVIpre-a (mL/m2) 19.3 6 5.6 21.6 6 6.8 40.2 6 12.9 66.2 6 28.9 <.001
TEVI (mL/m2) 12.5 6 3.8 11.6 6 3.9 17.9 6 6.1 14.0 6 7.5 <.001
PEI (mL/m2) 7.3 6 2.7 5.6 6 2.5 9.5 6 4.7 9.0 6 7.2 <.001
AEI (mL/m2) 5.1 6 1.8 6.1 6 2.2 8.4 6 2.6 5.0 6 1.4 <.001
Expansion index (%) 91.6 6 26.4 79.2 6 24.0 62.6 6 23.7 24.6 6 11.1 <.001
Diastolic emptying index 46.9 6 6.9 43.3 6 7.1 37.2 6 9.1 19.3 6 6.8 <.001
PE (%) 58.3 6 9.7 47.6 6 11.1 51.3 6 11.4 58.2 6 18.6 <.005
PEI (%) 27.5 6 7.0 20.9 6 6.8 19.2 6 6.6 11.4 6 5.5 <.001
AE (%) 41.7 6 9.7 52.4 6 11.1 48.7 6 11.4 41.8 6 18.6 <.005
AEI (%) 19.3 6 4.5 22.4 6 4.5 18.0 6 5.7 7.9 6 4.9 <.001
AE, Active emptying percentage of total emptying; AEI (mL/m2), active emptying volume index; AEI (%), active emptying index; ANOVA, analysis of
variance; PE, passive emptying percentage of total emptying; PEI (mL/m2), passive emptying volume index; PEI (%), passive emptying index; TEVI,
total emptying volume index.
conduit function and a compensatory increase in booster function investigators have reported that LAVImax linearly increases with the
with aging.15 Although controversy exists regarding the effect of aging severity of diastolic dysfunction grade using standard 2D9-11 and
on LA size,18,20-22 we found that LA volumes slightly, but three-dimensional7 echocardiography. We demonstrate that in addi-
significantly, increase with aging, which might correlate with the tion, there also is a relationship between LAVIminx and LAVIpre-
age-related changes that occur in LV diastolic properties (from normal a and the severity of diastolic dysfunction. Because the left atrium is
to reduced LV relaxation frequently observed in elderly healthy directly exposed to LV pressures during diastole, elevated LV
subjects). Interestingly, in this study, even mild degrees of diastolic pressures result in an increase in LA pressure to maintain adequate
dysfunction were associated with significant increases in LAVIpre-a LV filling.1-6,23,24 This compensatory LA pressure elevation leads to
and LAVImin, probably because of associated comorbidities in stretching of the LA wall, resulting in LA dilatation. Compared with
addition to the normal age-related changes. These results suggest the normal diastolic function group, the passive emptying volume
that pathologically associated LV relaxation abnormalities have index was significantly lower in patients with mild diastolic
more of an adverse impact on LA remodeling compared with dysfunction. The reduction of passive emptying volume is associated
age-related relaxation changes. with a compensatory augmentation of the active emptying volume
index. However, as the severity of diastolic dysfunction advances, this
mechanism no longer operates in an efficient manner, resulting in
Effect of Diastolic Dysfunction Grade on LA Volumes a reduction of LV filling volume at the expense of LA dilatation.
LA volumes progressively increased with the severity of diastolic These results clearly describe the close relationship that exists
dysfunction, which is in agreement with other studies.7-12 Several between diastolic dysfunction and LA volume changes.
966 Otani et al Journal of the American Society of Echocardiography
September 2010
Effect of Diastolic Dysfunction Grade on LA Function Two-dimensional speckle-tracking echocardiography is useful for the
From the LA volume waveforms generated by 2DSTE, several LA assessment of LA remodeling in patients with diastolic dysfunction.
functional indices can be easily obtained. Although LA volumes in-
creased linearly with the severity of diastolic dysfunction, LA reservoir
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