Left ventricular diastolic function is strongly correlated with active emptying of the left atrium: a novel analysis using three-dimensional echocardiography
Scherr et al. Cardiovascular Ultrasound
Left ventricular diastolic function is strongly correlated with active emptying of the left atrium: a novel analysis using three- dimensional echocardiography
Johannes Scherr 0
Philip Jung 2
Tibor Schuster 1
Lars Pollmer 0
Gert Eisele 5
Franz Goss 5
Jens Schneider 4
Martin Halle 0 3
0 Department of Prevention and Sports Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen , Georg-Brauchle-Ring 56, D-80992 Munich , Germany
1 Department for Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universitaet Muenchen , Munich , Germany
2 Medizinische Klinik und Poliklinik I, Klinikum der Universität München , Munich , Germany
3 Munich Heart Alliance , Munich , Germany
4 Universitäts Herz-Zentrum Freiburg - Bad Krozingen, Klinik für Kardiologie und Angiologie II , Bad Krozingen , Germany
5 Heart Center “Alter Hof” , Munich , Germany
Background: Increased left atrial (LA) dimensions are known to be a risk factor in predicting cardiovascular events and mortality and to be one key diagnostic tool to assess diastolic dysfunction. Currently, LA measurements are usually conducted using 2D-echocardiography, although there are well-known limitations. Real-time 3D-echocardiography is able to overcome these limitations, furthermore being a valid measurement tool compared to reference standards (e.g. cardiac magnetic resonance imaging). We investigated LA function and volume and their association to left ventricular (LV) diastolic function, using newly designed and validated software for 3D-echocardiographic analysis. This software is the first to allow for a sophisticated analysis of both passive and active LA emptying. Methods: We analyzed 2D- and 3D-echocardiographic measurements of LA volume and function in 56 subjects and compared the results between patients with normal LV diastolic function (NDF) (n = 30, 52 ± 15 years, BMI 24.7 ± 2. 6 kg/m2) and patients in which diastolic dysfunction (DDF) was suspected (n = 26, 65 ± 9 years, BMI 26.7 ± 3.7 kg/m2). Conclusions: Diastolic LV dysfunction results in a reduction in active LA emptying, which is more strongly associated with LV filling pressure than other previously investigated LA parameters.
Three-dimensional echocardiography; Left atrium; Left ventricular diastolic function
Heart failure (HF) with preserved ejection fraction
(EF) (HFpEF) significantly contributes to morbidity,
mortality and health care costs in both the U.S. and
Europe . Currently the best non-invasive diagnostic
strategies and criteria to characterize HFpEF have yet
to be determined, largely because opinions addressing
diagnostic strategy differ substantially between cardiac
associations [2, 3].
The left atrium (LA) seems to play a pivotal role in the
development of HFpEF, as LA size is strongly associated
with left ventricular (LV) diastolic function and is an
independent predictor of heart failure hospitalization in
subjects with preserved ejection fraction and coronary
heart disease [4, 5]. Suggested mechanisms of ventricular
filling modulation are strongly related to the reservoir,
conduit, and pump functions of the LA [6, 7].
As a potential tool in the measurement of LV diastolic
function, LA volume is considered to reflect the
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cumulative effects of filling pressure over time in terms of
atrial remodeling. This would be superior to the currently
used technique of measuring left ventricular inflow, which
only reflect the filling pressure at the time of
measurement . Therefore, LA volume seems to be a good
surrogate parameter for cardiovascular risk, as well as a
powerful predictor of cardiovascular outcomes [4, 8].
Left atrial size is clinically assessed by linear
2dimensional (2D) echocardiographic (2DE) measurements
in 2- and 4-chamber views, which provides a fairly good
estimation of the true dimension . Although this
measurement has been accepted as having sufficient clinical
feasibility and reliability, in recent years 3-dimensional
(3D) echocardiography (3DE) assessment has become
The 3D-echocardiographic measurements for chamber
quantifications have shown high correlations with the
gold standard of cardiac magnetic resonance imaging
(cMRI) and computed tomography (CT) [10–12]. In
contrast to cMRI and CT, which is costly both in terms
of time and money, 3DE is a relatively fast and
economical bedside method to assess LA size and function .
Furthermore, other LA parameters such as the left atrial
function – generated by both the passive early filling of
the left ventricle (LV) caused by the movement of the
valvular plane and the active atrial contraction – were
rarely analyzed until the introduction of 3DE.
In a recent study, it was shown that a decreased
contribution of active left atrial emptying to ventricular
filling during diastole was strongly predictive of adverse
cardiac events and death .
Therefore, we performed the first evaluation of
passive and active left atrial function and size using
newly designed, already validated software for
3Dechocardiographic analysis and its correlation with left
ventricular diastolic function [11, 12].
Sixty consecutive, randomly assigned subjects (14 women,
46 men) who underwent echocardiography with a
commercially available ultrasound system (iE33, Philips
Healthcare, Hamburg, Germany) were recruited from 1)
the out-patient clinic for Prevention and Sports Medicine,
Klinikum rechts der Isar, Technische Universitaet
Muenchen or 2) the Division of Cardiology, Department
of Medicine, Medizinische Klinik und Poliklinik,
LudwigMaximilians-Universität, Campus Innenstadt.
The study protocol was approved by the university’s
ethical board (Klinikum rechts der Isar der Technischen
Universitat Munchen) and the investigation conforms to
the principles outlined in the Declaration of Helsinki.
All participants gave written informed consent.
Inclusion criteria were age ≥18 years and written
informed consent. Exclusion criteria were significant
cardiac valvular disease (at least moderate (2nd degree)
mitral or aortic regurgitation or mitral stenosis), cardiac
arrhythmias or conduction abnormalities (e.g.
(intermittent) atrial fibrillation or flutter, left or right bundle
branch block (QRS duration >120 ms), pacemaker
rhythm, frequent premature beats), previous cardiac
surgery, reduced left ventricular ejection fraction (EF
<55 %), previous transcoronary ablation of septal
hypertrophy (TASH), acute coronary syndrome (ACS) within
four weeks or myocardial infarction within 2 months,
or severe pulmonary hypertension with clinical relevant
right ventricular impairment.
The participants were divided into the following
groups: (1) a control group consisting of subjects with
an E/e’mean < 8; and (2) subjects with an E/e’mean ≥ 8
and also maximal LA volume (LAVmax) ≥ 34 mL*m−2
and therefore meeting criteria for diastolic LV
dysfunction according to current guidelines using 2DE
[2, 3]. Study design aimed to include 30 subjects in
each group. Four participants were excluded because
of very poor image quality (as recommended by the
current guidelines ). In the group with normal
diastolic function (control group), mainly leisure time
athletes (all performance category ranging from hobby
sportspeople to former elite athletes, all being free of
any cardiovascular diseases) were examined who
presented within the Department of Prevention and
Sports Medicine for primary prevention purposes. In
the group with evidence of diastolic LV dysfunction,
mainly patients with heart failure with preserved
ejection fraction (HFpEF) were included (recruited both
in the Department of Prevention and Sports Medicine
and Division of Cardiology).
Hypertension was defined as previously described .
Hyperlipidemia was defined as a total fasting cholesterol
level of more than 6.21 mmol/L or use of lipid-lowering
Transthoracic echocardiographic investigations (standard
2D parasternal short- and long-axis images and apical 2-,
3- and 4-chamber views, and 3-dimensional
echocardiography) were conducted during end-expiratory apnea in a
left lateral decubitus position by experienced
echocardiographers in accordance to current recommendations .
Echocardiographic images were collected at all sites and
analyses were performed at the core laboratory at the
Department of Prevention and Sports Medicine.
Indexes of LA volumes for body surface area were
calculated as previously described with a variation of the
formula from DuBois :
2D echocardiography (2DE)
For 2D-echocardiography, a transthoracic broadband
S51 transducer (frequency transmitted 1.7 MHz, received
3.4 MHz, Philips Medical Imaging, Hamburg, Germany)
2D atrial size was assessed with the biplane method of
discs (modified Simpson’s rule) and the area-length
method from apical two- and four-chamber views as
recommended by the American Society of
Echocardiography . The maximal length of the LA was measured
at ventricular end-systole in an apical-four chamber
view. Maximal left atrial volume (LAVmax) was measured
at the ventricle end-systole just before opening of the
mitral valve. Minimal left atrial volume (LAVmin) was
measured at the end-diastole on ECG just before closure
of the mitral valve .
Peak velocities of trans-mitral inflow during early
filling (E), atrial contraction (A), and the deceleration time
of the E-wave velocity (DT) were measured in apical
four-chamber view using pulsed Doppler
echocardiography with positioning of the Doppler sample volume
perpendicular to the flow jet at the tips of the mitral
valve leaflets; E/A ratio was subsequently calculated. The
early diastolic mitral annular velocity (e’) was measured
at the septal side as well as the free LV wall of the mitral
annulus using tissue Doppler imaging on the
longitudinal axis in the apical 4-chamber view. E/e’med and E/
e’lat as well as E/e’mean (calculated as E/mean(e’med and
e’lat)) were subsequently calculated.
Diastolic function was graded as “normal” when E/
e’mean was <8 and “at least suggestive of diastolic
dysfunction” when E/e’mean was ≥8 and LAVmax was
≥34 mL*m−2 [2, 3, 19]. The latter one with evidence of
diastolic dysfunction was subdivided into the three
stages of diastolic dysfunction in accordance to the
classification of Khouri . Also in the current guidelines,
consistency between at least two indices is required to
make the diagnosis of a diastolic dysfunction . We
chose E/e’mean and LAVmax because these indices seem
to be feasible and reproducible . Furthermore,
LAVmax represents a marker of chronicity of elevated LA
pressure . Additionally, E/e’mean ratio seems to be
less age dependent than other indices and therefore also
suitable to compare groups with different mean ages
. An E/e’mean ratio <8 usually indicates normal LV
filling pressure .
Real-time 3D-echocardiography (RT3DE)
For each patient, RT3DE was performed directly after
2DE with a 3 to 1 MHz transthoracic matrix array
transducer (X3-1) in the harmonic mode from an apical
window to acquire full-volume 3D images in accordance
to the current recommendations . To encompass the
entire left heart into the real-time 3-dimensional
echocardiographic data set, a full volume up to 92° × 84° scan
was acquired from seven R-wave-triggered sub-volumes
during an end-expiratory breath-hold. The depth and
angle of the ultrasound scan sector were adjusted to the
minimal level still encompassing the entire left ventricle
and atrium. The temporal resolution of the data sets
ranged from 25 to 34 ms.
Analysis of systolic function of the left ventricle
(3D-EFLV) and left ventricular volumes (LV stroke volume
[LV-SV]) was performed as previously described .
3D LA volume (3D-LAV) was analyzed with RT3DE
software (4D LA Function, TomTec Imaging Systems,
Munich, Germany) as previously described (see Fig. 1)
[11, 12]. 3-dimensionally measured maximum left atrial
volume (LAVmax3D) was assessed at ventricular end
systole right before opening of the mitral valve by
semiautomatic tracing of the LA endocardial surface. Minimal
3-dimensionally measured volume (LAVmin3D) was
measured at ventricular end-diastole just after closure of the
mitral valve. Total stroke volume of the left atrium
(Total SV) was calculated as the difference between the
minimum and maximum left atrial volumes.
After manual setting of five to seven tracing points in
each view, the endocardial border was automatically
delineated, and the LAV was obtained automatically
throughout the heart cycle, resulting in LA volume-time
curves. LA appendages and the confluence of the
pulmonary veins were excluded from the tracing. Manual
corrections were made to modify the automatic tracings
in some subjects where necessary (inaccuracy of
endocardial automated detection). To differentiate between
early diastolic filling (E = LA passive emptying) and atrial
contraction (A = LA active emptying) a marker (preA)
was set at the moment of the second opening
component of the biphasic opening movement of the mitral
valve. Corresponding volume was defined as pre-atrial
contraction volume (VpreA). For LA, atrial stroke volume
(ASV) was calculated as LAVpreA − LAVmin3D. Total-EF
was calculated as (LAVmax3D − LAVmin3D)/LAVmax3D ×
100 %. True-EF was calculated as ASV/LAVmax3D × 100 %.
Left atrial conduit volume (LA-CV) was calculated as
followed: LA-CV = LV-SV − Total SV. Additionally,
LACV was expressed as percentage of LV stroke volume
(LA-CVrel) to present the magnitude of LA-CV on LV
3D LA size and function were interpreted blinded to
the 2D measurements of diastolic function.
Data analysis was performed using PASW Statistics 22.0
(SPSS Inc., Chicago IL, USA). For quantitative data, the
Fig. 1 3D image analysis (4D LA Function, TomTec Imaging Systems) depicting the performed measurements
mean, standard deviation and range or if more
appropriate (non-normally distributed data) the median and
interquartile range (IQR: 25th/75th percentile) were
reported for descriptive purpose. Assumption of normal
distribution of data was verified by using descriptive
methods (skewness, outliers and distribution plots) and
inferential statistics (Shapiro–Wilk test).
Non-normally distributed main outcome parameters
were logarithmically transformed prior to parametric
data analysis. Thus, relative effects of potential
explanatory variables were modeled. Back-transformation was
performed using simple exponential functions. Thus
back-transformation of regression coefficients gives an
estimate for the median relative change of outcome
measure by a one-unit increment of the corresponding
For correlation analyses of left ventricular inflow
parameters and parameters of left atrial function, Spearman
correlation coefficients (ρ) were calculated. Agreements
between 2D- and 3D-methods were assessed by the
We performed a receiver operating characteristics
(ROC) analysis with participants meeting criteria for
diastolic LV dysfunction (E/e’mean ≥ 8 and also maximal LA
volume (LAVmax) ≥ 34 mL*m−2) as event of interest and
various quantities of the 3D assessment as potential
predictors. Areas under the ROC curve (AUCs) and
corresponding 95 % confidence intervals are presented. For
the most important measures (True-EF, Total-EF, and
ASV) the ROC curves are shown.
For analysis of the interobserver variability,
measurements were performed by two blinded observers. To
assess intraobserver variability, measurements were repeated
2 weeks later by an observer blinded to the previous
measurements. Inter- and intraobserver variabilities
were calculated as the difference between the two
measurements in terms of the percentage of their mean.
A p-value <0.05 was considered to indicate statistical
significance. Testing was performed two-sided.
Baseline characteristics and 2-dimensional
echocardiographic data are presented in Table 1.
In the group with evidence of diastolic dysfunction
(n = 26), 14 (54 %) had impaired relaxation (stage I
diastolic dysfunction), 7 (27 %) had pseudonormal
function (stage II diastolic dysfunction) and 5 (19 %) had a
reversible restriction (stage III diastolic dysfunction).
Normal diastolic function
(E/e’mean < 8) n = 30
With evidence of diastolic LV dysfunction
(E/e’mean ≥ 8 & LAVmax ≥ 34 mL/m2) n = 26
Table 1 Baseline characteristics of participants
Body mass index [kg/m2]
Fat Free Mass [kg]
Body surface area [m2]
Cardiovascular Risk Factors
Left ventricle internal diameter, diastole [mm]
Posterior wall thickness, diastole [mm]
Septum wall thickness, diastole [mm]
3-dimensional echocardiographic parameters
No significant between-group differences were observed
in left atrial dimensions (both minimal and maximal
volume and total stroke volume) when measured with 2DE
and 3DE. However, there were significant differences in
volumes caused by active left atrial emptying, like ASV
and true atrial ejection fraction (see Table 2 and Fig. 2).
In these investigations, the group with suspected
diastolic dysfunction had decreased atrial stroke volume
(median [IQR]: 3.0 [0.1–4.5] ml vs. 5.5 [2.7–7.8] ml,
p = 0.005), also when corrected for BSA and BMI,
respectively. Furthermore, the true ejection fraction was
significantly lower in the group with diastolic
impairment (7.3 vs. 16.2 %, p = 0.002).
These significant associations between E/e’mean and LA
volumes were also supported in univariate and
multivariate linear regression models. In the correlation analysis
there were highly significant inverse associations between
E/e’mean and parameters of active left atrial emptying
(correlation coefficients: ASV: ρ = −0.472; True EF ρ = −0.488,
all p < 0.001). In contrast, total left atrial function
(represented by Total SV and Total-EF) was not different
between the groups (all p > 0.05). There were no significant
associations between 2-dimensionally measured (such as
A or a’ wave) and 3-dimensionally assessed (e.g. ASV)
parameters of active LA emptying (all p > 0.05).
In ROC analyses, True-EF showed the highest AUC
(0.753 (0.623–0.883)), followed by ASV (0.731 (0.598–
Table 2 3D-echocardiographic characteristics (volumetric and functional) of the left atrium
Normal diastolic function
(E/e’mean < 8) n = 30
With evidence of diastolic LV dysfunction
(E/e’mean ≥ 8 & LAVmax ≥ 34 mL/m2) n = 26
LAVmax3D/BMI (ml × m2 × kg−1)
LAVmin3D/BMI (ml × m2 × kg−1)
Total SV/BSA (ml/m2)
Total SV/BMI (ml × m2 × kg-1)
ASV/BMI (ml × m2 × kg-1)
0.865)) and Total-EF (0.605 (0.452–0.758)). These AUCs
were not significantly different between the examined
parameters (p-value ranging from 0.114 to 0.409). ROC
curves are presented in Fig. 3.
In regression analyses, total SV (β = −0.024, p = 0.862)
and LAVmax3D (β = 0.125, p = 0.357) showed weak
associations to E/e’mean, whereas LAVmin3D showed a modest
association (β = 0.196, p = 0.148). ASV showed the
strongest association (β = −0.421, p = 0.001). Also after
adjustment for age, blood pressure, heart rate and LV mass,
active atrial emptying (ASV) remained strongly
associated with E/e’mean in a linear regression model including
all LA volumes (see Table 3).
The correlation coefficients ranged from 0.90 (ASV) to
0.99 (LAVmin3D and LAVmax3D) between measurements
(performed by one observer, intra-observer variability)
and from 0.90 (ASV) to 0.99 (LAVmin3D) between
observers (inter-observer variability). Cronbach’s Alpha
ranged from 0.90 (ASV) to 0.99 (LAVmin3D).
Agreement of 2D- and 3D- determined left atrial volumes
Agreement of 2-dimensionally and 3-dimensionally
measured left atrial volumes are presented within
BlandAltman correlation (see Fig. 4). The left atrial volume
measured 2-dimensionally using the Simpson method
seems to overestimate the volume compared to the
3dimensionally measurement. In contrast, LA volume
analyzed with the area-length technique resulted in smaller
sizes when compared to 3D measurements.
Our study is the first to analyze both active and passive
LA emptying components with regard to diastolic
We were able to detect differences between a group
with normal diastolic function compared to a group with
participants representing with diastolic dysfunction with
regard to active LA emptying. In contrast, all other
parameters of LA volume showed no significant
differences. Therefore, it can be assumed that using 3DE with
special focus on active LA emptying might result in
Fig. 3 ROC curves for True-EF, ASV and Total-EF with respect to
participants meeting criteria for diastolic LV dysfunction (E/e’mean ≥ 8
and also maximal LA volume (LAVmax) ≥ 34 mL*m−2) as event of interest
we also found LAVmin3D to better correlate with LV
diastolic function than LAVmax3D. However, the newly
investigated parameters of LA function (True-EF and
ASV) showed even stronger associations and seem
therefore to be a more sensitive instrument to measure
small but meaningful alterations of diastolic function.
One reason for this reduction during active LA
emptying might be the decreasing compliance of the left
ventricle with progressive filling at end-diastole in patients
with impaired diastolic LV function .
Regarding another three-dimensionally assessed
parameter (relative LA conduit volume) which was prior linked
to diastolic dysfunction , we were not able to
demonstrate an association between increased LA-CVrel and
impaired diastolic LV function. However, the populations
between our study and the cohort of Nappo et al. differ
significantly (e.g. LV-EF: 60.1 ± 9.3 % vs. 37.1 ± 11.3 %) and
LV stroke volume and EF play a decisive role in the
calculation of LA-CVrel and determination of impaired diastolic
LV function , the results of these two studies cannot
be compared. Therefore, further studies are needed with
Table 3 Linear regression of left atrial volumes with E/e’mean
−0.03 (0.05) −0.08
−0.07 (0.05) −0.19
LAVmin3D 0.05 (0.047) 0.17 0.20 −0.02 (0.05) −0.08
Values represent parameter estimates (B), standard errors (SE), and
standardized parameter estimates (β)
aAdjusted for age, heart rate, hypertension and left ventricular mass
Fig. 2 LA volumes and function in the investigated groups.
* indicating p = 0.005, †indicating p = 0.09, ‡ indicating p = 0.002
earlier and more sensitive diagnosis of diastolic
dysfunction compared to conventional approaches.
New parameters and left ventricular diastolic function
In a recent study, Russo et al. observed that minimum
LA volume was closer correlated to LV diastolic function
than maximum LA volume . This is in accordance
with our results. In the multivariate regression analysis,
larger numbers of participants to be able to calculate
reference values which can be generalized.
In another recent study on 2-dimensional evaluation
of LA volumes and function, Teo et al. observed that in
subjects in the initial stages of diastolic dysfunction, the
active emptying volume is increased compared to
subjects with normal diastolic function . However, as
the grade of LV diastolic dysfunction increases, this
compensatory mechanism reduces and is eventually lost
as mechanical atrial dysfunction sets in, resulting in a
lower total LA emptying volume. Similar results were
observed by Prioli et al., while investigating left atrial
volumes and function with 2D-echocardiography and
left ventricular catheterization . This is consistent
with the current study in which nearly half of the
participants had higher stages of diastolic dysfunction;
however, we were able to observe decreases in active LA
emptying even at the very early stages of diastolic
dysfunction. The reason behind this might be due to the
fact that the analyses of the LA volumes in both of the
aforementioned studies were conducted with
conventional 2D methods, which are known to be less precise
then CMR imaging or 3D echo . Furthermore, in the
study of Prioli et al., left atrial volume and function were
estimated based on 2D-measured ventricular filling
volumes and mitral flow patterns.
Similar results to those of Teo and Prioli were
demonstrated in a study of Murata et al., who were able to show
in cases of impaired relaxation, an initial increase in active
LA emptying followed by a decrease of active LA
emptying in the stages of pseudonormalisation and restriction
(and vice versa regarding passive LA emptying) .
However, in studies assessing left atrial volumes
3dimensionally, the software application tool (QLAB,
Philips Medical System, Andover, Massachusetts) used
was originally designed for analysis of LV volumes.
Therefore, the analysis of these studies might be less
precise compared to the software we used and which
was specifically designed for volumetric analysis of the
left atrium .
Clinical implications of new LA parameters
Studies investigating the impact of left atrium as a
prognostic marker concentrate mainly on maximum LA
volume [6, 27, 28]. This parameter can be assessed easily
with 2D-echocardiography, and therefore there is a large
amount of data available.
However, newer studies suggest that other measures of
left atrium dimensions and function (e.g. minimum LA
volume or ejection fraction) have higher prognostic
impact and a closer correlation to left ventricular diastolic
function than maximum LA volume [5, 14, 22, 29].
Especially LA function has attracted scientific attention
recently. Epidemiologically, left atrial function seems to
play an important role as a risk factor in all-cause
mortality. In particular, LA True-EF seems to be superior to
LAVI with respect to cardiovascular death but also
allcause mortality even after adjustment for traditional
cardiovascular risk factors and LV parameters .
Therefore, future studies investigating the impact of
left atrial volumes and function should focus on novel
and easily accessible LA markers such as total left atrial
function and active left atrial emptying. These markers
can be determined validly with the new method
including the software used in the current study and correlate
well with conventional markers of diastolic function.
Limitations and strengths
It can certainly be argued that our study included a
relatively small number of participants and data should be
validated by larger patient cohorts. However, the sample
was heterogeneous (both randomly selected healthy
subjects referred to the out-patient clinic and seriously ill
patients consulted in by cardiologists in a University
Hospital were included) and therefore representative.
Therefore, the findings of our study can be generalized.
Secondly, we did not perform direct measurements of
LV end-diastolic pressure because this requires invasive
procedures. However, we used Doppler-derived E/e’ ratio
as a surrogate parameter of LV end-diastolic pressure.
This method is routinely used in clinical settings and
studies and has been clinically validated [30, 31].
Additionally, we refrained from strain or speckle LA
analyses, which are parameters investigated in the context
of diastolic function most recently [32, 33]. However,
these investigations would go beyond the scope of the
current paper and might reduce the clarity. Therefore,
this might be a topic of future analyses.
Furthermore, recording of the total duration of the
diastole was not possible due to the modality of
acquisition which required a record of seven subsamples to
attain a sufficient resolution. Therefore, LAVmin could not
be measured with complete assuredness. However, there
are two studies demonstrating that the measurement of
minimum LA volume assessed by the new software
correlated excellently with the gold standard measurements
(cardiac magnetic resonance imaging and computed
tomography) [11, 12]. Especially in the study of Mor-Avi
et al. cMRI and 3D-echocardiography showed identical
results regarding LAVmin (bias: 0 ml, r = 0.88) . In
the study of Rohner et al., LAmin measured by RT3DE
was even lower than measured by CT . Therefore,
we are confident that the data for LAmin measured with
RT3DE are valid. Furthermore, this limitation would be
relevant for both the NDF and DDF groups, leaving the
results based on group differences unbiased in this aspect.
Nevertheless, future studies should examine whether a
significant difference between the left atrial volumes
analyzed in loops covering the whole diastole also exists.
However, there are several strengths of the current
study. First of all, state-of-the-art techniques (e.g.
3Dechocardiography and tissue Doppler imaging) were
used. The 3-dimensional examination procedure of left
cardiac dimensions and function has been demonstrated
to be superior to 2-dimensional investigations [12, 21].
Another strength of our study is the use of a novel, yet
validated software tool which was specifically designed
for detailed assessment of both left atrial volumes and
dimensions. This software allows sophisticated analyses
of both passive and active emptying of the left atrium,
which allowed for the new results of the present study.
Lastly, our study was conducted with a multi-centre
setting and therefore has greater general applicability
than single-centre studies.
Diastolic dysfunction causes a reduction in active left
atrial emptying which is more strongly associated to left
ventricular filling pressure than maximum or minimum
left atrial volume.
The investigational software package used in this study was provided free of
charge by TomTec Imaging Systems, Unterschleissheim, Germany.
The study was primarily designed by JSche. JSche, MH and PJ represent the
principal investigators. All other authors contributed to the design of the
study and supervised the trial. Data acquisition was conducted by JSche, PJ,
GE, FG and JSchn. The statistical analysis plan and statistical analysis of the
data were made by TS, JSche and LP. The first author (JSche) wrote the first
draft of the manuscript, which was next revised in detail by MH. Subsequent
drafts were prepared by all authors. JSche has the primary responsibility for
There are neither financial relationship with the organization that sponsored
the research nor any other financial interests. The authors had full control of
all primary data and they agree to allow the journal to review their data if
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