3D Echo systematically underestimates right ventricular volumes compared to cardiovascular magnetic resonance in adult congenital heart disease patients with moderate or severe RV dilatation
Journal of Cardiovascular Magnetic Resonance
3D Echo systematically underestimates right ventricular volumes compared to cardiovascular magnetic resonance in adult congenital heart disease patients with moderate or severe RV dilatation
Andrew M Crean 0 1
Neil Maredia 2
George Ballard 2
Ravi Menezes 1
Gill Wharton 2
Jan Forster 2
John P Greenwood 3
John D Thomson 2
0 Division of Medicine (Cardiology), Peter Munk Cardiac Centre, Toronto General Hospital , Toronto, Ontario , Canada
1 Department of Medical Imaging, University of Toronto , Toronto, Ontario , Canada
2 Division of Adult and Pediatric Cardiology, Leeds General Infirmary , Leeds , UK
3 Academic Unit of Cardiovascular Medicine, Leeds General Infirmary , Leeds , UK
Background: Three dimensional echo is a relatively new technique which may offer a rapid alternative for the examination of the right heart. However its role in patients with non-standard ventricular size or anatomy is unclear. This study compared volumetric measurements of the right ventricle in 25 patients with adult congenital heart disease using both cardiovascular magnetic resonance (CMR) and three dimensional echocardiography. Methods: Patients were grouped by diagnosis into those expected to have normal or near-normal RV size (patients with repaired coarctation of the aorta) and patients expected to have moderate or worse RV enlargement (patients with repaired tetralogy of Fallot or transposition of the great arteries). Right ventricular end diastolic volume, end systolic volume and ejection fraction were compared using both methods with CMR regarded as the reference standard Results: Bland-Altman analysis of the 25 patients demonstrated that for both RV EDV and RV ESV, there was a significant and systematic under-estimation of volume by 3D echo compared to CMR. This bias led to a mean underestimation of RV EDV by -34% (95%CI: -91% to + 23%). The degree of underestimation was more marked for RV ESV with a bias of -42% (95%CI: -117% to + 32%). There was also a tendency to overestimate RV EF by 3D echo with a bias of approximately 13% (95% CI -52% to +27%). Conclusions: Statistically significant and clinically meaningful differences in volumetric measurements were observed between the two techniques. Three dimensional echocardiography does not appear ready for routine clinical use in RV assessment in congenital heart disease patients with more than mild RV dilatation at the current time.
Monitoring of serial change in right ventricular (RV) size
and function is of fundamental importance for physicians
caring for patients with paediatric and adult congenital
heart disease (ACHD) [1,2]. Two dimensional
echocardiography is used extensively for this purpose but is
inadequate for assessment of the complex geometry of
the right ventricle without mathematical modelling .
Cardiovascular magnetic resonance (CMR) has become
the reference standard for the measurement of right
ventricular size, geometry and function. CMR benefits from
excellent reproducibility of volumetric measurements of
both ventricles and does not depend on a suitable
acoustic window. However availability of CMR is limited and it
can not be performed in the outpatient clinic or at the
Recently, three dimensional echocardiographic (3D
echo) techniques have been introduced which are capable
of acquiring a real time volumetric data set using ordinary
commercially available echocardiography systems. Such
data can be rapidly collected at the bedside and can be
processed off-line in a similar manner to CMR data. If
accurate and reproducible, this modality could simplify
serial data collection in patients known to be at risk of the
deleterious effects of right heart dilation and dysfunction.
The purpose of this study was to report our initial
experience of 3D trans-thoracic echo as a possible alternative to
CMR in an ACHD population with a range of right
ventricular volumes and functional abnormalities.
Patients were recruited in a prospective, consecutive
manner from the Adult Congenital Heart Disease out-patient
program at our institution. Patients were eligible if they
had undergone a CMR examination in the preceding 12
months, or if the responsible physician indicated that
CMR exam would be performed in the subsequent 6
months. Recruitment was restricted to 3 groups; those
with previously repaired Tetralogy of Fallot (ToF) in
infancy or childhood (without subsequent pulmonary
valve replacement); those with a right ventricle in the
systemic position (e.g., Senning, Mustard or congenitally
corrected transposition patients) and those with repaired
coarctation (CoA) of the aorta. Patients within the first 2
groups were expected to have a range of RV dilatation and
dysfunction, and for the purpose of analysis were treated
as a single group. The coarctation group were included as
an internal control arm with the expectation that right
ventricular size and function would be normal or
nearnormal. The study was approved by the Institutional
Review Board and all subjects gave written informed
All patients underwent a full 2D trans-thoracic
echocardiogram with particular focus on the right ventricle
according to the recommendations of the American
Society of Echocardiography . All images were acquired
by 2 British Society of Echocardiography-accredited
sonographers with over 40 years of echocardiography
experience between them (JF, GW). The standard 2D clinical
examination was followed by additional full volume 3D
image data acquisition (Philips IE33, Phillips Medical
Systems, The Netherlands) by one of two experienced cardiac
sonographers. Three dimensional image acquisition was
performed from modified standard views (most often
apical 4 chamber) in order to maximize visualization of
the RV. The 3D echo datasets were analysed offline on a
dedicated workstation (TomTec v1.2, TomTec Imaging
Systems, Germany). Two dimensional multiplanar
reconstructions of the RV were semi-automatically generated
with manual correction to produce data sets in the short
axis, four chamber and RV inflow-outflow orientation.
End diastole and end-systole were selected manually by
review of individual image phases and contouring was
performed by semi-automatic border detection after manual
placement of key seed points to define the RV apex and
tricuspid annular plane (Figure 1). Resulting contours
were checked for accuracy and corrected as necessary.
Precise details of this process with the TomTec software
package have been published recently .
CMR examinations were performed on a Philips 1.5 T
Intera magnet (Philips Medical Systems, The Netherlands).
Steady state free precession (SSFP) images were acquired
in the short axis plane from the atrioventricular groove to
the cardiac apex. Cine acquisitions were performed with
vectorcardiographic ECG gating over 6-10 heartbeats at
held end-inspiration. Technical parameters were: slice
thickness 8 mm no gap, 25 cardiac phases, TR 3.2 ms, TE
1.6 ms, FoV 320 320 cm, reconstruction matrix 256
256 cm. CMR studies were analysed offline using QMass
V6.1 software (Medis, The Netherlands). All RV contours
were performed on the short axis cine stack from the
pulmonary valve to the RV apex, with trabeculation
assigned to the blood pool . Selection of end systole/
diastole was performed manually by visual assessment of
smallest/largest RV cavity size in each cardiac phase. RV
volumes were calculated by the method of summated
discs according to Simpsons rule .
Data are presented as mean ( SD). Descriptive statistics
were used for normally distributed data. Non parametric
statistics were employed to compare differences in
volumes and function where appropriate. Fishers exact
test was used for the comparison of proportions.
Intraand inter- observer analysis were tested for both
techniques after an interval of 8 weeks by the original readers
and a further reader analyzing a random selection of 50%
of the cases from each imaging modality. Intra-class
correlation coefficients were calculated to rate both inter and
intra-observer variability in measurements of RV size and
function. The method of Bland and Altman was used for
assessment of systematic bias between methods of
measurement . P < 0.05 was taken to indicate statistical
Twenty nine patients were recruited to the study over a 12
month period. Three patients failed to complete the study
due to CMR-related claustrophobia and in 1 patient 3D
Figure 1 Off line processing of 3D echo data. Reconstructions are performed to generate images in 4 chamber, short axis and right
ventricular inflow-outflow views. Contours are applied in all 3 planes at end systole and diastole and propagated in a semi-automatic fashion
across all acquired time points. This allows generation of a time-resolved volume rendered image of the right ventricle (see Additional File 1:
supplementary video file) and also a time volume curve from which functional data are obtained.
echo was unsuccessful due to a combination of difficult
echo window and extreme cardiac rotation. The study
group was therefore comprised of 25 patients who
underwent both 3D echo and CMR within a mean of 12 weeks
of each other. Seven patients had a diagnosis of CoA, 14,
had ToF and 4 had a diagnosis of complete transposition
of the great arteries (TGA) palliated with either a Mustard
or Senning procedure. The mean age was not significantly
different between the 2 groups (CoA 26 yrs vs ToF/TGA
27 yrs p = ns). Detailed patient characteristics are given in
Table 1. There were no significant differences between the
2 groups for patient body surface area or time between
CMR and 3D echo examinations.
Using CMR as the reference standard, there was a clear
difference in RV size between the CoA group and the
mixed lesion group (ToF and TGA). As expected,
patients with a diagnosis of ToF or palliated TGA had
significantly larger right ventricular end diastolic and end
systolic volumes (EDV and ESV) than the patients with
repaired CoA; the RV ejection fraction was also
significantly lower in the former group (Figure 2).
Compared to CMR, 3D echo significantly
underestimated volumes in the 25 patients as a whole, although the
difference in measured RV ejection fraction (EF) was not
significant (Figure 3). Mean RV end diastolic volumes
were significantly greater when measured by CMR
compared to 3D echo (236 (107) ml vs. 169 (78) ml; p < 0.01).
Mean RV end systolic volumes were also significantly
greater by CMR compared to 3D echo (146 (85 ml) vs. 98
(60) ml; p < 0.05). However, mean RV EF was not
statistically different between the 2 modalities (40% (10%) vs.
44% (11%) for CMR and 3D echo respectively; p = 0.09).
Bland-Altman analysis of the 25 patients demonstrated
that for both RV EDV and RV ESV, there was a
significant and systematic under-estimation of volume by 3D
echo compared to CMR (Figure 3). This bias led to a
Table 1 Patient demographics and cardiovascular pathology of the study group
Data presented as mean (SD) or absolute values. CoA, aortic coarctation; ToF, Tetralogy of Fallot. BSA, body surface area.
mean underestimation of RV EDV by -34% (95%CI:
-91% to + 23%). The degree of underestimation was
more marked for RV ESV with a bias of -42% (95%CI:
-117% to + 32%). There was also a tendency to
overestimate RV EF by 3D echo with a bias of approximately
13% (95% CI -52% to +27%).
When patient data were examined by disease grouping,
a different pattern was seen with respect to volumetric
measurements (Table 2). Large differences were observed
between volume measurements in the ToF and TGA
patients with a mean underestimation by 3D echo
compared to CMR in RV EDV of -80 ml (bias -36%; 95%CI:
-99 to +27%). However 3D echo in the CoA group
demonstrated a much smaller mean underestimation of
only -35 ml (bias -27%; 95%CI: -12 to +67%). End systolic
volume was also underestimated by 3D echo in the ToF
and TGA patients (mean difference -64 ml; bias -45%;
95%CI: -123 to +32%), but, again, to a lesser extent in the
CoA group (mean difference -21 ml; (bias -34%; 95%CI:
-104 to +35%). RV ejection fraction by 3D echo was
Figure 2 a-c - Comparative RV volumes & function by modality. Comparison of RV volumes and function between the mixed lesion (ToF
and TGA) group and the CoA group. Boxes represent median and inter-quartile ranges and whiskers are the 95%CI.
Figure 3 a-i - Systematic differences between modalities for all patients combined. Groups comparison, correlation and Bland Altman
analysis of difference in RV volumes and function as measured by both CMR and 3D echocardiography. Boxes represent median and
interquartile ranges and whiskers are the 95%CI. Bland Altman plots demonstrate mean bias (dot-dash line) and 95% CI (dotted lines).
marginally more accurate in the CoA group than in the
ToF/TGA group (mean bias +3.8% 95%CI: -17 to +25%
versus +6% 95%CI: -10 to +22% respectively).
Finally, both intra- and inter-observer variability were
significantly lower for CMR than for 3D echo (Table 3).
The right ventricle is a complex geometric structure which
unlike the left ventricle does not benefit from relative
symmetry around its long axis. There are numerous published
techniques for echocardiographic measurement of RV
function [9-13]. However, conventional 2 dimensional
echo techniques commonly underestimate the true size of
the adult right ventricle . This is a particular problem in
Adult Congenital Heart Disease (ACHD) populations,
since many surgical and interventional procedures may be
considered even in asymptomatic patients based on certain
volumetric thresholds. Furthermore, patients with
functionally impaired single or systemic right ventricles may
develop heart failure syndromes once the EF drops below
35%, emphasizing the relevance of accurate EF-derived
risk stratification . Accurate knowledge of poor EF is
Table 2 Absolute quantitative RV volumes and ejection fraction according to imaging technique and disease grouping
(n = 25)
3D Echo EDV (ml)
3D Echo ESV (ml)
Data presented as mean (SD).
Table 3 Intra class correlation coefficients for inter and intra-observer variability according to technique
crucial in this patient group since it results in closer
monitoring and follow up, more aggressive medication and
pacing strategies, and - where appropriate - earlier referral
for transplant assessment.
Three dimensional echocardiography offers the
promise of accurate measurement of the RV without the
need for geometric assumptions. Three dimensional
echo is not a new technique - both in vitro and animal
studies have shown efficacy in the measurement of left
ventricular structures [15,16]. Further studies have
demonstrated the utility of the technique for the
assessment of left ventricular structures in both children 
and adults . However the left ventricle is a
geometrically less complex structure than the right ventricle and
it is thus better served by the mathematical
underpinnings of 3D echocardiography.
Although there are right ventricular data from 3D echo
in the pediatric age range, there are only isolated studies
in the literature which have attempted to validate 3D echo
in adult populations with congenital heart disease [19,20].
Our study was a direct comparison of trans-thoracic 3D
echo versus CMR as the reference standard for
measurement of right ventricular end-diastolic and end-systolic
volumes and derived ejection fraction. We deliberately
included adult patients with repaired tetralogy of Fallot
since the majority of these have had prior patch
enlargement of the RV infundibulum with disruption of the
pulmonary valve annulus resulting in severe pulmonary
incompetence and progressive RV dilatation over time.
The severity of RV dilatation in ToF patients in our study
was significant though not extreme, with a mean EDV of
270 ml (corrected by body surface area to a mean RV
EDV index of 153 ml/m2). One currently available
retrospective study suggests a threshold of 180 ml/m2 at which
pulmonary valve replacement (PVR) should be considered
. In reality, there is considerable variation in threshold
for surgical referral for PVR from center to center as well
as on a patient to patient basis . Nonetheless it is
important that the selected measurement methodology
should be accurate and reproducible within the range of
moderate to severe RV dilatation.
The inclusion of several patients with transposition of
the great arteries and Mustard/Senning repair was merited
as these patients have the right ventricle located in the
subaortic position. This inevitably leads to secondary
hypertrophy and wall thickening, as well as
atrio-ventricular valve regurgitation and secondary systemic ventricular
enlargement. Serial assessment of the systemic ventricle in
these patients is imperative as progressive decline is often
an indication for more aggressive therapies including heart
CMR has been shown to have excellent reproducibility
for measurement of both LV and RV size and function
, and this was again confirmed for the right ventricle
in our study, despite the relative severity of dilatation.
Our results with regard to the accuracy and
reproducibility of 3D echo, however, are less positive than
reported in the published literature.
Earlier work comparing RV volume measurement by
both transthoracic and transesophageal 3D techniques
have demonstrated excellent correlations between the 3D
echo measurements of RV volume and function compared
to both CMR and radionuclide ventriculography .
However, this patient population was more heterogeneous
than ours and included only a single patient with
pathology associated with RV dilatation (secundum ASD).
Review of their data reveals that the mean (SD) RV EDV
by CMR was only 109 (34) ml, uncorrected for BSA, with a
maximum EDV of just 191 ml. This compares with an
uncorrected mean (SD) and maximum in our series of 236
(107) ml, and 509 ml respectively. Despite the relatively
small RV cavity sizes included, Nesser et al observed: ...on
the Bland-Altman scattergram....a tendency for TEE-3D
and TTE-3D to underestimate large RV volumes
compared with MRI... - as such their data are entirely
concordant with our findings in much larger RVs.
Recently, Grewal et al examined 25 patients with
tetralogy of Fallot using both CMR and 3D echo . Although
they demonstrated better correlations between the two
modalities for RV volumes than in our own study, they
nonetheless describe a systematic underestimation of both
RV EDV and ESV by a maximum of up to 36%. As in our
study and that of Nesser et al, the greatest discrepancy
between the two techniques occurred in patients with
larger right ventricles, particularly above a threshold of
250 ml for EDV.
Further comparable work was published recently by
Arnould et al in an adult population suffering from
assorted cardiomyopathies . The mean RV EDV by
CMR in that study was 171 (69) ml but this was severely
underestimated by 3D echo at only 77 (42) ml. End
systolic volume was also significantly underestimated by a
mean of almost 60 ml (ESV CMR 105 (55) ml vs. ESV
3D echo 46 (32) ml).
Our results with 3D echo are similarly disappointing
with respect to patients with right ventricular enlargement
due to congenital heart disease. As we hypothesized,
measurements made by CMR and 3D echo were comparable
in the coarctation patient group who had normal RV size.
However the patient group in whom 3D echo potentially
has the most to offer, those with an enlarged RV (e.g. the
ToF and TGA groups), demonstrated relatively poor
comparison to CMR for volumetric indices. Furthermore 3D
echo would have been falsely reassuring with respect to
RV ejection fraction in a number of patients in this study.
The reasons for the limited accuracy and reproducibility
of 3D echo are likely to be multi-factorial: the spatial
resolution of 3D echo in full volume mode is substantially
lower than that of the native 2D application; limited lateral
spatial resolution results in poorly-defined fuzzy
endocardial borders in diastole, and creates genuine difficulty in
separating endocardium from trabeculation at end-systole.
This specific point was touched on in detail in a
thoughtful editorial by Mor Avi et al who point out that a similar
difference in recorded volume between the 2 techniques is
also seen for the left ventricle but that this difference may
be substantially reduced if CMR-contouring is performed
in such a manner as to exclude the trabeculation from the
blood pool (which is generally the opposite of current
practice) . In other words current conventions of
contour drawing tend to favour high resolution techniques
like CMR in comparisons against lower resolution
methods . As Mor Avi poignantly comments: the devil is in
the boundary .
Secondly, the right ventricle may be difficult even in a
normal individual to fully encompass within a pyramidal
volume as is required during 3D image acquisition. In
many cases the available sector width is simply inadequate
for the size of the ventricle, leading to poor or incomplete
endocardial definition in the reconstructed views, with
adverse effects on the accuracy of contour definition.
Future technical developments will no doubt address the
difficulties imposed by sector angle limitations. Thirdly, a
proportion of patients may have difficult acoustic windows
regardless of RV size. Not infrequently this is related to
musculoskeletal abnormalities, such as pectus excavatum,
which are often seen in patients with congenital heart
Finally, a degree of selection bias undoubtedly plays a
role in published data. We deliberately included all but
one patient in our analysis; this patient was excluded as
the 3D echo image quality was so poor that no attempt at
contouring could be made. However one recent
publication comparing manual versus automated border detection
of 3D echo (versus CMR) in a similar population to ours
documented a 48% exclusion rate from data analysis in 54
consecutive patients scanned, because of inadequate image
quality . The authors explain that they found, as we
did, that difficulties in imaging the near field by 3D echo
results in poor definition of the anterior free wall of the
right ventricle with potential inaccuracies for extrapolation
of the endocardial contour. Although the findings of these
authors were undoubtedly improved by limiting their
analysis to good quality data sets, the need to exclude half the
recruited sample would preclude translation of this
technique into routine clinical practice.
We acknowledge several limitations to our study. Firstly
our sample size was relatively small (though not dissimilar
to the published literature in this area) and in particular
lacked power to clearly define the progressive limitations
of 3D echo in reference to graded increases in RV
end-diastolic volume. Secondly, although our patient recruitment
was prospective and consecutive the 3D echo was not
performed on the same day as the CMR study; however the
mean time difference was only 12 weeks between studies
in which time one would not expect any significant
systematic change in RV cavity size in a stable outpatient
population. Thirdly, since 3D echo currently acquires a
pyramid of data over multiple sequential heartbeats we
did not attempt to recruit any patient who was not in
sinus rhythm. This is also a relative limitation of CMR
which generally requires a stable R-R interval for routine
segmented cine imaging. Fourthly we acquired CMR
images in end-inspiration rather than end expiration as is
done more routinely. This is because 3D echo windows
were generally superior at end-inspiration and we wished
to match the two techniques as far as possible. Limited
volunteer data suggests this entails a risk of over-sampling
the RV since the end inspiratory position of the
diaphragm may vary by as much as 25% . However the
risk of scanning the same slice twice on sequential
breatholds as a result is mainly a problem for scanning in the
axial plane. We contoured the RV from the short axis
plane in order to obviate this concern. Finally, we
acknowledge a greater experience with both acquisition
and post-processing of CMR images than 3D echo, which
may have introduced a learning bias into our results. This
is, however, the case whenever a new modality is
compared to an existing reference standard and, as shown
above, our results are not discordant with those seen in
several studies of both adult congenital and acquired heart
This study provides further data describing a clinically
important underestimation of RV volume by 3D echo,
particularly in a patient subgroup with moderate or
severe enlargement. We observed a systematic
underestimation of both RV EDV and ESV when compared to
CMR to an extent which has clinical relevance. The
degree of underestimation may provide false reassurance
to both patient and physician, and could have an
adverse impact on appropriate clinical decision making.
3D echo is a new and rapidly evolving modality which
may in the near future be able to offer the twin benefits of
portability and comparable accuracy to CMR. Many factors
contributing to the relative inaccuracy of 3D echo are
technical issues that will be addressed by further research and
product development. However current data suggest
caution is warranted when using 3D echo as the principal
imaging modality in patients with any greater than mild RV
dilatation. Physicians caring for patients in whom
management decisions are based upon possession of accurate
volumetric data need to be aware of the current limitations in
3D echocardiography. Our data, and others, support the
contention that CMR - for the time being at least - remains
the standard of reference in this population.
Additional file 1: Movie 1. A typical example of the 4D model of the
right ventricle derived from a trans thoracic 3D echocardiography study.
The authors wish to acknowledge Dr Kate English for her support of the
study and also the Childrens Heart Surgery Fund, Leeds which enabled
purchase of the TomTec software used in this study.
AMC, JT and JDT were responsible for study design. AMC, JDT and GB
recruited patients for the study. GW and JF performed the 3D echo on all
the patients included in the study. AMC and NM performed the CMR
analysis. AMC and GB performed the 3D echo analysis. AMC and RM were
responsible for the statistical analysis. All authors read and approved the
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