European Journal of Echocardiography (2009) 10, 287–294
doi:10.1093/ejechocard/jen237
Age and body surface area dependency of mitral valve
and papillary apparatus parameters: assessment
by real-time three-dimensional echocardiography
Carolin Sonne1, Lissa Sugeng1, Nozomi Watanabe2, Lynn Weinert1, Ken Saito2, Miwako Tsukiji2,
Kiyoshi Yoshida2, Masaaki Takeuchi3, Victor Mor-Avi1, and Roberto M. Lang1*
1
3
University of Chicago Medical Center, Chicago, IL 60637, USA; 2Kawasaki Medical School, Kurashiki, Japan; and
Tane General Hospital, Osaka, Japan
Received 9 April 2008; accepted after revision 25 August 2008; online publish-ahead-of-print 16 September 2008
KEYWORDS
Mitral valve;
Papillary muscles;
Echocardiography
Aims Real-time three-dimensional echocardiography (RT3DE) has been used to quantify mitral valve
(MV) annular size and leaflet tenting parameters in small numbers of patients with different pathologies. We sought to establish normal values for RT3DE mitral annular, tenting, and papillary muscle parameters over a wide age range and to study their age and body surface area (BSA) dependency.
Methods and results Transthoracic wide-angled RT3DE images of the MV were acquired in 120 subjects
(52 females, 68 males, age: 37 + 20 years) with normal left ventricular (LV) function, no risk factors,
and less than or equal to mild mitral regurgitation. Custom software (RealVieww) was used to trace
the MV annulus, leaflets, and the papillary apparatus in mid-systole in 18 sequential cut planes obtained
from the 3D data sets. Mitral valve annular area and height as well as tenting parameters (maximum and
mean tenting height and mid-systolic tenting volume) were obtained and correlated with age and BSA.
Wide inter-subject variability was noted in all parameters. Despite this variability, parameters directly
affected by LV size were found to be BSA-dependent: MV annular area showed highest correlation
with BSA (r ¼ 0.78), followed by inter-papillary distance (r ¼ 0.58) and postero-medial (PM) and
antero-lateral (AL) papillary muscle annular distance (r ¼ 0.57 and r ¼ 0.46, respectively). Age did
not correlate with either annular or tenting parameters, but showed moderate negative correlation
with inter-papillary muscle angle (r ¼ 20.52) and mild negative correlation with inter-papillary
distance (r ¼ 20.32), both normalized by BSA.
Conclusions Real-time three-dimensional echocardiography-derived MV annular, tenting, and papillary
muscle parameters vary widely in normal subjects. When used clinically, normal values of parameters
that are age- and/or BSA-dependent need to be adjusted accordingly.
Echocardiography has contributed significantly to the understanding of normal and abnormal mitral valve (MV) physiology.1–3 This is despite the fact that assessment of the MV
apparatus using two-dimensional (2D) echocardiography is
difficult and experience-dependent because it requires
mental integration of multiple imaging planes.4 To overcome
these limitations, three-dimensional (3D) echocardiography,
based on techniques, such as magnetic or acoustic tracking
and gated sequential acquisition, has been used to
improve the visualization of the mitral apparatus and quantify MV orifice size.5–9 However, 3D echocardiography has not
been routinely used in clinical practice because previous
* Corresponding author.
E-mail address: [email protected]
techniques required offline reconstruction and lengthy
data analysis.9
More recently, transthoracic real-time three-dimensional
echocardiography (RT3DE) was used to quantify MV annular
size and leaflet parameters in small numbers of patients
with MV prolapse, ischaemic and dilated cardiomyopathy,
mitral stenosis, and bioprosthetic valves.4,10–15 The main
advantage of this methodology is the rapid image acquisition
and fast quantification. Despite the relatively large number
of published studies, there are no established RT3DE-derived
normal reference values for the mitral apparatus geometry.
Moreover, the relationship between such normal values and
age and/or body habitus remains unknown. Accordingly, we
sought: (i) to establish RT3DE-derived normal values of the
mitral annulus, leaflet parameters, and papillary muscle
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2008.
For permissions please email: [email protected].
288
length and position over a wide range of ages and (ii) to
determine whether these parameters are age- and body
surface area (BSA)-dependent.
Methods
Patient population
A total of 123 subjects of both genders in a wide range of ages were
prospectively screened, including 62 patients recruited at University of Chicago Hospitals and 61 patients at Kawasaki Medical
School and Tane General Hospital. Inclusion criteria were: normal
global and regional left ventricular (LV) function [ejection fraction
55% and no evidence of regional wall motion abnormalities
(RWMA)], absence of risk factors for coronary artery disease, and
less than or equal to mild mitral regurgitation. Prior to recruitment,
all patients underwent a transthoracic 2D echocardiographic study
to rule-out RWMA and valvular heart disease. All participants gave
written informed consent, which was approved by the Committees
for the Protection of Human Subjects in Research at each
institution.
Transthoracic 3D echocardiography
A SONOS 7500 scanner (Philips, Andover, MA, USA) equipped with a
fully sampled matrix array transducer (X4) was used for RT3DE
acquisition from the apical window with the patient in the lateral
decubitus position. Full-volume acquisition in the wide-angled
C. Sonne et al.
mode combining four ECG-triggered wedge-shaped sub-volumes
(938 218) was used to obtain RT3DE data sets during a single
breath-hold. Care was taken to include the entire MV apparatus
with the papillary muscles in the pyramidal data set. Frame rates
were 16–22 frames/s, depending on imaging depth (12–16 cm). At
each participating institution, image acquisition was performed by
a single experienced sonographer. The volumetric data sets were
digitally stored on magneto-optical disks and then transferred into
a personal computer for offline analysis.
Quantification of mitral valve and papillary
muscle parameters
Custom software (RealVieww, YD, Nara, Japan) was used to analyse
the volumetric data sets. Initially, mid-systole was identified and
the anterior-posterior (AP) as well as the medial-lateral (ML) plane
of the mitral annulus initialized on the respective cut planes selected
from 18 sequential planes spaced 10º apart (Figure 1A and B).
Subsequently, the surfaces were manually traced in each plane and
the papillary muscles were identified by first initializing the
mid-portion of the anterior mitral annulus at the aortic root level,
followed by the postero-medial (PM) and antero-lateral (AL) papillary
muscle tips (Figure 1C). Anatomical 3D images of the mitral annulus
and leaflets, as well as the papillary muscles, were then automatically reconstructed in the 3D space (Figure 1D).
From these 3D images, several parameters of MV shape were
calculated (Figure 1D), including: (i) MV annular area, (ii) MV
annular circumference, (iii) MV annular diameter (AP and ML), and
(iv) MV annular height (Figure 1D, left), with the latter used as a
Figure 1 Quantification of mitral valve and papillary muscle parameters. (A and B) The three-dimensional (3D) volumetric image was automatically cropped into 18 equally spaced radial planes. (C ) We manually marked the mitral annulus (cyan dots) and traced the leaflets (cyan
lines) in each cropped plane in mid-systole. In addition, papillary muscle tips were identified (cyan dot, C, right). From these data, 3D images
of the mitral annulus and leaflets, as well as the papillary apparatus, were then reconstructed automatically (D), and used to quantify parameters of both mitral valve shape and papillary muscle geometry (see text for details).
RT3DE quantification of the mitral apparatus
289
non-planarity index of the saddle-shaped mitral annulus. To quantify
MV leaflet tenting, the saddle-shaped mitral annulus was projected
onto a plane, while maintaining the distance between the leaflets
and the mitral annulus. This display was used to quantify mean
and maximum MV leaflet tenting height and leaflet tenting
volume, as previously described.10–12 Maximum tenting height was
calculated as the distance from the annular plane to the most
distant tethering site of the leaflet (Figure 1D, right). Mean
tenting height was calculated as the average distance between
the annular plane and the tethered leaflet. Tenting volume was
defined as a volume enclosed between the annular plane and the
mitral leaflets.
In addition, several parameters of the papillary muscle apparatus
were measured (Figure 1D, middle), including: (i) papillary muscletethering distance from both PM and AL papillary muscle tips to the
relatively fixed fibrous portion of the anterior mitral annulus (PM
and AL papillary muscle annular distance), (ii) inter-papillary
muscle distance measured between both PM tips, and (iii) papillary
muscle angle measured between the two lines connecting anterior
mitral annulus and papillary muscle tips.
Statistical analysis
Statistical analysis was performed using Microsoft Excel. Data were
expressed as mean + SD. For each measured parameter, the
relationship with age, BSA, and height was calculated using the
Pearson correlation coefficient. In addition, to assess the reproducibility of mitral apparatus quantification, analysis was repeated in 15
randomly selected patients 1 month later by the same observer who
was blinded to the results of any previous measurements. For each
parameter, intra-observer variability was calculated as the absolute
difference between the two readings, in per cent of their mean, and
averaged over the 15 patients. In addition, coefficient of variation
was calculated for each parameter as the SD of the differences
between repeated measurements in per cent of their mean.
Results
Of the initial 123 patients studied, 98% (120 patients: 52
females, 68 males, age: 37 + 20 years, range 3–85 years,
BSA: 1.68 + 0.33 m2, range 0.58–2.35 m2) had 3D images of
the MV apparatus adequate for analysis. The papillary
muscle analysis could not be performed in 29 patients (24%)
due to inadequate visualization of the papillary muscle tips.
Table 1 summarizes the normal values of the mitral
annular and leaflet parameters as well as papillary muscle
measurements, including the correlations with age and
BSA. Wide inter-subject variability was noted in all parameters, including mitral annular non-planarity, which was
present in most normal subjects as reflected by annular
height of 4.3 + 2.1 mm and leaflet tenting height of 1.9 +
1.5 mm. Mitral valve diameter in the anterior-posterior
axis was 30.8 + 4.4 mm (range: 19.9–45.4 mm), whereas in
the medial-lateral dimension it was slightly larger: 35.1 +
4.9 mm (range: 23.5–49.4 mm).
Female patients in our study were slightly younger and
had lower BSA than their male counterparts (32 + 18 vs.
40 + 20 years and 1.57 + 0.32 vs. 1.77 + 0.31 m2, respectively). Despite these differences, when correcting for BSA,
there were no gender differences in MV leaflet and papillary
muscle parameters, with the exception of annulus diameter:
medial-lateral diameter/BSA: 22.23 + 3.86 mm/m2 for the
males vs. 20.69 + 3.00 mm/m2 for the females (P ¼ 0.02)
and annular height/BSA: 2.29 + 1.3 vs. 2.77 + 1.05 mm/m2,
respectively (P ¼ 0.03). When correcting for both age and
BSA, there were no significant differences between female
and male patients in the MV leaflet and papillary muscle
parameters.
Parameters directly affected by LV size were found to be
BSA-dependent. Mitral valve annular area and circumference showed the highest level of correlation with BSA (r ¼
0.78 and 0.81, respectively, Table 1 and Figure 2), followed
by inter-papillary distance (r ¼ 0.58), PM and AL papillary
muscle annular distance (r ¼ 0.57, 0.46, respectively,
Figure 3). For most parameters, correlations with height
were similar to those with BSA (Table 1). As demonstrated
in Figures 2 and 3, age did not correlate with annular or
tenting parameters, but showed a moderate negative correlation with inter-papillary muscle angle (r ¼ 20.52) and
with inter-papillary distance (r ¼ 20.32), when normalized
by BSA (Table 2).
Reproducibility data in terms of range of differences
between repeated measurements in individual patients,
intra-observer variability, and coefficients of variation are
summarized in Table 3.
Discussion
In this study, we used transthoracic RT3DE imaging to evaluate multiple parameters of the MV apparatus, in a large
number of subjects over a wide spectrum of ages. Several
observations were made in this study, including: (i) the nonplanarity of the saddle-shaped mitral annulus in mid-systole
is widely variable in normal subjects over a wide range of
ages, (ii) the position of the papillary muscles in 3D space
Table 1 Mitral valve and papillary muscle apparatus parameters: correlation with body surface area
MV annular area (cm2)
Mitral annular circumference (mm)
Mitral annular height (mm)
Max. tenting height (mm)
Mean tenting height (mm)
Mean mid-systolic tenting volume (cm3)
Inter-papillary muscle angle (º)
PM papillary muscle annular distance (mm)
AL papillary muscle annular distance (mm)
Inter-papillary distance (mm)
Mean + SD
Range
Correlation w/BSA (r)
Correlation
w/height (r)
Correlation with age after
normalization for BSA (r)
8.6 + 2.2
10.5 + 1.4
4.3 + 2.1
5.3 + 2.4
1.9 + 1.5
1.5 + 0.9
28.0 + 7.5
37.6 + 7.8
35.4 + 8.2
17.7 + 4.8
3.9–15.6
7.0–14.0
0.5–9.4
1.9–12.9
20.93–7.1
0.2–5.5
8.8–44.2
20.2–53.9
17.8–54.1
5.7–37
0.78
0.81
0.27
0.31
0.00
0.41
0.08
0.57
0.46
0.58
0.72
0.76
0.32
0.20
0.02
0.31
0.01
0.58
0.70
0.51
0.13
20.20
0.20
0.05
0.07
0.15
20.52
20.04
0.07
20.32
290
Figure 2
C. Sonne et al.
Correlations of mitral valve parameters with BSA and age (shown with linear regression line and 95% confidence intervals).
in relation to the MV apparatus in normal human hearts was
relatively uniform irrespective of age; (iii) MV annular and
papillary muscle parameters are BSA-dependent; and (iv)
there were no significant gender-related differences in
age- and BSA-corrected MV annulus, leaflet, and papillary
muscle parameters.
In our study, RT3DE measurements of the MV apparatus
were in agreement with previously reported values.
As previously described, in normal subjects, the mitral
annulus has a non-planar saddle shape configuration, with
its lowest points located at the commissures, and its
highest points near the aortic root and near the posterior
LV wall. Although transthoracic 2D echocardiography can
provide reasonable estimates of mitral annulus diameter in
adults,16 it is difficult to quantify multiple parameters due
to the complexity of the MV and sub-valvular structures.
Several studies have emphasized the importance of the
precise visualization of the geometry of the MV–LV apparatus
using RT3DE, particularly when trying to elucidate the
aetiology of mitral regurgitation with its direct implications
for MV repair.10–14 Real-time three-dimensional echocardiography is ideally suited to accurately evaluate the structure
of the mitral apparatus, including the LV chamber and papillary muscle position. Using methodology similar to this
study, Watanabe et al.10 demonstrated that the MV
annulus is saddle-shaped in healthy subjects and reported
that mean saddle height and annular circumference were
similar to those reported in our study. The saddle-shaped
mitral annulus has been postulated to play an important
role in minimizing peak mitral leaflet stress.17–20 This physiological concept has led to surgical strategies to restore the
normal saddle shape of the mitral annulus.21–23
RT3DE quantification of the mitral apparatus
291
Figure 3 Correlations of papillary muscle parameters with BSA and age (shown with linear regression line and 95% confidence intervals).
292
C. Sonne et al.
Table 2 Mitral valve and papillary muscle apparatus parameters normalized by body surface area: correlation with age
MV annular area/BSA (mm2/m2)
MV annular circumference/BSA (mm/m2)
Mitral annular height/BSA (mm/m2)
Max. tenting height/BSA (mm/m2)
Mean tenting height/BSA (mm/m2)
Mean mid-systolic tenting volume/BSA (cm3/m2)
Inter-papillary muscle angle/BSA (degrees/m2)
PM Papillary muscle annular distance/BSA (mm/m2)
AL Papillary muscle annular distance/BSA (mm/m2)
Inter-papillary distance/BSA (mm/m2)
Mean + SD
Range
Correlation w/age (r)
5.1 + 0.8
6.4 + 1.1
2.6 + 1.2
3.2 + 1.3
1.2 + 0.9
0.9 + 0.5
17.6 + 9.1
22.3 + 5.6
21.0 + 5.8
10.5 + 3.3
3.4–7.0
2.1–12.4
0.3–6.5
1.0–3.2
20.5–3.7
0.3–3.1
7.12–52.6
13.9–38.3
11.1–32.5
4.6–23.4
0.13
20.20
0.20
0.05
0.07
0.15
20.52
20.04
0.07
20.32
Table 3 Reproducibility of the mitral valve and papillary muscle parameters obtained by analysis of repeated measurements in 15
randomly selected patients
MV annular area (cm2)
Mitral annular circumference (mm)
Mitral annular height (mm)
Max. tenting height (mm)
Mean tenting height (mm)
Mean mid-systolic tenting volume (cm3)
Inter-papillary muscle angle (degrees)
PM papillary muscle annular distance (mm)
AL papillary muscle annular distance (mm)
Inter-papillary distance (mm)
Range of differences between
measurements
Intra-observer
variability (%)
Coefficient of
variation (%)
0.01–1.47
0.00–0.85
0.03–0.91
0.10–1.67
0.02–2.33
0.02–0.94
0.32–9.04
0.05–2.69
0.01–3.78
0.04–4.03
5.7
2.6
11.6
7.5
20.2
16.5
6.4
4.5
4.0
6.1
5.3
2.5
11.2
7.7
26.1
17.1
7.1
2.5
3.1
5.3
In our study, in relatively large group of normal subjects
evenly distributed over a wide range of ages (Figures 2 and
3, right columns), the mitral leaflets appeared nearly flat
with minimal tenting. The mean tenting volume was higher
than that previously reported in a small group of 10 normal
subjects10 (1.5 + 0.9 vs. 0.45 + 0.29 cm3), possibly due to
the differences in the number of patients and their age distribution. Despite the wide inter-subject variability of MV and
papillary muscle parameters observed in this study, those
directly affected by LV size showed a significant BSA dependency. These parameters included MV annular size, MV circumference, inter-papillary muscle distance, and PM
papillary muscle annular distance. Although previous investigators have reported normal values for the geometry of the
mitral annulus using multiplane transoesophageal echocardiography images in a small group of patients,24 to our knowledge, our study is the first to report BSA-dependency of
RT3DE-derived MV and papillary muscle parameters. Current
reference values for MV size are based on 2D echocardiographic and Doppler measurements, assuming flat circular
geometry of the MV annulus, whereas the saddle shape of
the MV apparatus can be precisely measured from RT3DE
images. Several parameters of the LV have been stratified
by BSA and age by 2D echocardiography to establish reference
values. These include chamber size, wall thickness, and aortic
root size as well as atrioventricular valve orifice area.25–29
The size of the MV annulus in children using 2D echocardiography has been shown to have a logarithmic relationship
to BSA.29 In contrast, our results using RT3DE showed a
linear relationship with increasing body size in MV and papillary muscle parameters, which are also directly affected by
LV size. These differences may be due to the fact that King
et al. studied only children (age 1 day to 15 years), with a
lower BSA range from 0.2 to 1.4 m2 (median 0.45 m2). In
contrast, our study group consisted of normal subjects,
age 3–85 years, with a BSA range of 0.58–2.35 m2. It is
likely that in the higher BSA range, MV dimensions may
show a more linear relationship to BSA. Similarly to our
results, Poutanen et al.,30 using reconstructed 3D images
obtained in children and young adults, age 2–27 years with
BSA . 1.5 m2, also showed a linear relationship between MV
dimensions and increasing BSA. The mean + SD ratio
between the MVA/BSA in our patients was 5.1 + 0.8 cm2/m2.
This ratio was similar to that reported by Poutanen et al.30
who measured a mean MVA/BSA of 4.8–5.5 cm2/m2, depending on BSA range, in their patients. In contrast to prior 2D
echocardiographic studies,28 our RT3DE study did not show a
significant correlation between age and MV annular or
tenting parameters, together with a negative correlation
between age and inter-papillary muscle angle.
To our knowledge, this study is one of the first to assess
the papillary muscle position in 3D space with RT3DE in
humans. This entity is extremely important for the understanding of the 3D geometry of the entire mitral apparatus.
Only a few studies have evaluated the displacement of the
papillary muscles in the evaluation of mitral regurgitation
RT3DE quantification of the mitral apparatus
in animals with RT3DE.31–33 Our study has shown the feasibility of papillary muscle geometry analysis in 76% of
healthy children and adults.
Limitations
RT3DE images are often of lower quality than conventional
2D echocardiographic images. As the software used in the
present study requires identification of mitral annulus, leaflets, and papillary muscles, technically inadequate RT3DE
images could not be analysed. However, our data are
similar to prior studies that have shown that the submitral
apparatus is only visible in 70–80% of consecutive patients.15
Further improvements in imaging technology are necessary
to enhance the resolution of the RT3DE images for improved
visualization of the papillary muscles. In addition, the software used in this study measures the inter-papillary
muscle angle. In the evaluation of ischaemic MR, it is
important to evaluate the asymmetry of papillary muscle
displacement, which is not possible with this technique.
The timing of measurements may affect the estimates of
annular size. Studies have reported cyclic variations in
mitral annular shape and area.19,34 The dimension of the
mitral annulus is maximal and most eccentric at the time
of normal maximal atrial volume. Similar to other RT3DE
studies of the MV apparatus, we made mitral annular
measurements in mid-systole.10–12 Therefore, it is important
that inter-study comparisons of MV geometry take into
account the timing of measurement in the cardiac cycle.
Moreover, different to previous reports, our study was performed on a large group of patients with a wide range of
BSA and ages, which makes direct comparisons between
our findings and those of previous investigators difficult.
Despite these limitations, data presented in this paper on
the geometry of the MV and papillary muscle apparatus in
this large group of healthy children and adults support
further use of RT3DE in adults with various heart diseases.
Conclusions
As echocardiographic assessment of the MV in 3D space for preoperative planning becomes increasingly quantitative, it is
important to determine normal values of valve geometry
over a wide range of ages. To address this need, our study
was designed to provide RT3DE reference values for various
components of the MVapparatus in normal subjects of different
ages. Importantly, our data revealed wide inter-subject variability in normal RT3DE-derived MV annular geometry, leaflet
tenting, and papillary muscle position in 3D space. Despite
this variability, parameters directly affected by LV size were
found to be BSA-dependent. Interestingly, age did not correlate
with either annular or tenting parameters. Establishing reference values for MVand papillary muscle parameters that incorporate BSA-dependencies are especially important in the
clinical setting, where RT3DE may become part of the routine
echocardiographic examination and RT3DE measurements
will be available for clinical decision-making.
Conflict of interest: R.M.L. received an equipment grant from
Philips Medical Systems.
293
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