The limited usefulness of real-time 3-dimensional echocardiography in obtaining normal reference ranges for right ventricular volumes
The limited usefulness of real-time 3-dimensional echocardiography in obtaining normal reference ranges for right ventricular volumes
Erlend Aune 1
Morten Baekkevar 1
Olaf Rodevand 0
Jan Erik Otterstad 1
0 Department of Cardiology , Feiringklinikken, Feiring , Norway
1 Department of Cardiology, Vestfold Hospital Trust , Box 2168, NO-3103 Toensberg , Norway
Background: To obtain normal reference ranges and intraobserver variability for right ventricular (RV) volume indexes (VI) and ejection fraction (EF) from apical recordings with real-time 3dimensional echocardiography (RT3DE), and similarly for RV area indexes (AI) and area fraction (AF) with 2-dimensional echocardiography (2DE). Methods: 166 participants; 79 males and 87 females aged between 29-79 years and considered free from clinical and subclinical cardiovascular disease. Normal ranges are defined as 95% reference values and reproducibility as coefficients of variation (CV) for repeated measurements. Results: None of the apical recordings with RT3DE and 2DE included the RV outflow tract. Upper reference values were 62 ml/m2 for RV end-diastolic (ED) VI and 24 ml/m2 for RV end-systolic (ES) VI. Lower normal reference value for RVEF was 41%. The respective reference ranges were 17 cm2/m2 for RVEDAI, 11 cm2/m2 for RVESAI and 27% for RVAF. Males had higher upper normal values for RVEDVI, RVESVI and RVEDAI, and a lower limit than females for RVEF and RVAF. Weak but significant negative correlations between age and RV dimensions were found with RT3DE, but not with 2DE. CVs for repeated measurements ranged between 10% and 14% with RT3DE and from 5% to 14% with 2DE. Conclusion: Although the normal ranges for RVVIs and RVAIs presented in this study reflect RV inflow tract dimensions only, the data presented may still be regarded as a useful tool in clinical practice, especially for RVEF and RVAF.
Right ventricular (RV) function is an important prognostic
factor in both congenital and acquired heart disease .
In clinical practice the assessment of right ventricular
dysfunction is important to a variety of conditions . As
early as 1982 an attempt was made to determine RV
volume from the apical window by 2-dimensional
echocardiography (2DE) using the Simpson's biplane method .
In that study, however, only "body" volumes were
obtained, reflecting inflow tract dimensions which
represented 55% of the total RV volume as obtained by RV
angiography. In order to compensate for these problems,
Levine et al.  incorporated a combination of apical
four-chamber (for inflow) and subcostal views (for
outflow). This approach, however, has not gained widespread
acceptance within clinical practice. According to present
guidelines, assessment of RV size is best performed in the
apical 4-chamber view, with reference limits provided for
both RV diastolic and systolic areas and for RV area
fraction (AF) . The introduction of real-time 3-dimensional
echocardiography (RT3DE) has provided promising
results for RV volume measurements from one single
modified apical view using offline analysis with Tomtec
3D software by disc summation .
The recent introduction of RT3DE with fast online
analysis may allow bedside measurements of RV volumes and
ejection fraction (EF). The purpose of the present study
was to obtain normal reference values for RV volumes and
EF with RT3DE parallel to reference ranges for
2DEderived areas corrected for body surface area (BSA). In
addition, a blinded and unblinded reproducibility study
of the two methods was carried out.
Recruitment of participants
The aim was to include 15 to 20 males and females, all
employed (past and present) at our hospital, per age
decade from 30 to 80 years. An invitation was sent to 250
potential participants. All had to give informed written
consent in order to be given an appointment for a
screening visit. A total of 195 persons came to this visit, which
included a 2DE examination to exclude subclinical
cardiac abnormalities such as significant valvular disease
(stenosis or aortic-/mitral regurgitation >1/3) or apparent
abnormalities of cardiac chambers. 29 individuals were
excluded for various reasons, including; antihypertensive
use (n = 14), new diagnosis of hypertension (repeated
blood pressure > 160/90 mmHg, n = 3), malignant
disease (n = 2), a history of coronary heart disease (n = 1),
treatment for arrhythmia (n = 1), congenital heart disease
(n = 1), diabetes mellitus (n = 1), poor image quality (n =
1), left bundle branch block (n = 1), large atrial septal
aneurysm (n = 1), chronic pericardial effusion (n = 1).
Two subjects who had given their written consent did not
attend the screening. BSA was calculated according to the
DuBois et DuBois formula .
The study was approved by both the Regional Ethics
Committee of the South-Eastern Norway Regional Health
Authority and the Norwegian Social Science Data Service.
All examinations were performed using a Philips IE 33
with 3D QLab advanced software (version 6) installed.
According to the manufacturer this software was modified
to include both left ventricular and atrial volumes as well
as RV volume calculations.
2DE measurements of RV areas (A) in end-diastole (ED)
and end-systole (ES) were established from the apical
4chamber view, with simple planimetry allowing the
calculation of RV area fraction (AF). Harmonic RT3DE imaging
was performed using a 3-matrix array transducer with the
participant in the left lateral decubitus position. A
wideangled "full-volume" acquisition mode, in which
wedgeshaped subvolumes are obtained over 45 consecutive
cardiac cycles, was used during held respiration in
endexpirium. Both an apical 4-chamber view of the RV and an
orthogonal view were extracted from the pyramidal
dataset in the same manner as applied for LV and atrial
recordings . Five anatomic landmarks were then manually
initialized, including two points to identify the tricuspid
valve annulus in each of the two apical views and one
point to identify the apex in either view. Following
manual identification of these points, the program
automatically identified the 3D endocardial surface using a
deformable shell model.
The orthogonal view, however, was not obtainable in all
participants. In addition, the automatic border detection
occasionally included various parts of the right atrium as
well. The criteria for a successful recording were both a
clear delineation of the RV cavity in both apical views and
the exclusion of the right atrium. If that could not be
obtained within three attempts then the participant was
excluded from the study. Adjustments of the automatic
surface detection, in order to include all trabeculae in the
RV cavity that could be visualized, were done without
exception in the two apical views. End-diastolic volume
(EDV) was automatically computed from voxel counts.
Thereafter, end-systole (ES) was selected by identifying
the frame with the smallest RV dimension. Surface
detection, including initialization and editing, was repeated on
this frame to obtain the ESV. RVEF was calculated from
Figure 1 presents RV in ED and figure 2 RV in ES, and
demonstrate the two apical views, the short axis view, the
resulting 3D model of the RV cavity obtained, and
thetime volume curve. The performance of these
measurements took approximately five to six minutes per
A: Blinded study
Two to four weeks after the initial study a repeated 2DE
and RT3DE examination was performed on 20
participants (7 males and 13 females) selected at random. One
examiner did all 2DE recordings (EA) and another all
RT3DE recordings (JEO). Since we wanted to accurately
reflect the scenario as in daily clinical practice, the
repeated study was done blindly and without access to
previous images or results. With both methods care was
RFVigutrraeci1ngs after editing in end-diastole
RV tracings after editing in end-diastole. Top: The two long axis orthogonal views. Middle the short axis view (left) and
3D model of LV (right). Bottom: time- volume curve, indicationg that these measurements are taken from the maximal
dimension (white vertical line to the left).
taken to include trabeculae in the RV cavity. This study
only allowed us to evaluate intraobserver variability for
the two investigators. In order to replicate clinical practice
the presented 2DE data are taken from only one heartbeat
during both examinations.
B. Unblinded study
This study was performed in order to optimize the
reproducibility with both methods. 22 participants were picked
at random (9 females and 13 males). All had given their
informed consent to undergo two new separate
echocardiographic examinations which were performed within a
mean interval of five days. None of these persons had
participated in the blinded study.
been properly trained to carry out this method,
interobserver variability data could not be obtained.
These examinations and measurements were performed
by the same investigator of the RT3DE recordings (JEO).
Data were transferred to an EchoPAC analysis system (GE
Healthcare). Offline RV tracings were performed by both
investigators (JEO and EA) in order to obtain both
intraand interobserver variability. Loops and tracings from the
first examination were available during the second, and
all values presented are the mean of three heartbeats. To
obtain the single plane measurements with three manual
tracings per variable took approximately 510 minutes.
The same investigator (JEO) did all examinations and
measurements. RV endocardial tracings, after manual
editing from the first examination, were available during
the second examination. Since only one investigator had
Paired and unpaired t tests were used for comparison of
continuous data between groups of subjects. Two-tailed
pvalues below 0.05 were considered statistically significant.
Upper normal limit was calculated as mean +2 standard
SFiimguilarret2racings in end-systole, with the time volume curve indicating the minimum dimension (white vertical line in the middle)
Similar tracings in end-systole, with the time volume curve indicating the minimum dimension (white vertical
line in the middle).
deviations (SD) and lower normal limit as mean -2SD.
Pearson's correlation was used for analyses on
relationship between volumes and age.
The intra- and interobserver variability for repeated
RT3DE and 2DE measurements has been expressed as
coefficient of variability (CV). The CV was calculated as
the SD of the differences divided by the mean of the
parameter under consideration . All analyses were
implemented using SPSS 16.0 (SPSS Inc, Chicago, IL).
Baseline characteristics and reproducibility
The characteristics of the 166 participants (87 females and
79 males) are shown in table 1. Only seven participants
were aged 70 years or more. Therefore the two oldest
decades are pooled. Apart from the larger body size in males,
there were no statistically significant differences between
males and females. A small mitral regurgitation was found
in 29% of participants, whilst 6% had a small aortic
regurgitation and 3% had both. Predefined successful
measurements of RV volumes were obtained in 156 (95%)
RT3DE RV volumes and EF (table 2)
In the entire study group upper normal values were 62 ml/
m2 for RVEDVI and 28 ml/m2 for RVESVI, whereas lower
RVEF was 41%. Lower normal values were 18 ml/m2 for
RVEDVI and 4 ml/m2 for RVESVI, whilst upper normal RV
EF was 81%. Males had higher upper normal RVEDVI and
RVESVI when compared to females, whilst they had a
lower reference limit for RVEF.
Weak but statistically significant negative correlations
were found between age and RVEDV (r = -0.28, p = 0.001)
and age and RVESV (r = -0.21, p = 0.009). RVEF, however,
did not correlate significantly with age.
Categorical data are presented as n (%). Continuous data are presented as mean standard deviation or median (25th75th percentile).
2DE RV areas and AF (table 3)
Upper normal values were 17 cm2/m2 for RVEDAI and 11
cm2/m2 for RVESAI. The lower normal limit for RVAF was
27%. The respective lower normal values were 9 cm2/m2
for RVEDAI and 3 cm2/m2 for RVESAI. Upper RVAF was
63%. Males had a higher upper normal limit for RVEDAI
when compared to females, but a similar reference for
RVESAI and a lower reference limit for RVAF. There were
no significant correlations between age and RV areas or
A. Blinded study: The CVs for intraobserver variability
were 37% for RVEDV, 33% for RVESV and 26% for
B. Unblinded study: The respective CVs were 10% for
RVEDV, 14% for RVESV and 13% for RVEF.
A. Blinded study: The CVs for intraobserver variability
were 16% for RVEDA, 17% for RVESA and 22% for
B. Unblinded study: The CVs for intraobserver
variability (average of examiner 1 and 2) were 6% for
RVEDA, 13% % for RVESA and 12% for RVAF. The CVs
for interobserver variability (average of examinator 1
and 2) were 6% for RVEDA, 10% for RVESA and 11%
The present study has provided gender-specific normal
reference ranges for both RV volumes and EF measured
Table 2: Right ventricular volumes and ejection fraction obtained with real-time 3-dimensional echocardiography (RT3DE) according
to age group and gender.
Continuous data presented as mean standard deviation. RV: right ventricular, EDV: end-diastolic volume, ESV: end-systolic volume, EF: ejection
fraction, I: index.
Table 3: Right ventricular areas and area fraction obtained with 2-dimensional echocardiography from a single plane four-chamber
view according to age group and gender.
Continuous data presented as mean standard deviation. RV: right ventricular area. A: area. D: diastolic. S: systolic. I: index. AF: area fraction.
with RT3DE and 2DE-derived RV areas and AF corrected
for BSA. In addition, we observed a negative correlation
between age and RV dimensions with RT3DE, but not
with 2DE. The intraobserver variability, however, was
poor with blinded measurements using both methods,
indicating that follow-up measurements of individual
patients should be performed after careful inspection of
previous loops and tracings of the RV endocardium. This
dataset has been obtained from a large population of
healthy volunteers, each of whom was carefully screened
for disease, including subclinical cardiac disorders.
During the progress of this study, the outflow tract,
including the pulmonary artery valves, was not visualised
in any of the examinations. This corresponds with the
problems reported in previous 2DE studies using the
apical approach [3,4].
The notion of an underestimation of RV volumes in our
study is verified from reference values in studies
incorporating offline analysis allowing inclusion of the RV
outflow tract. In Gopal et al's.  study of 71 healthy
individuals upper normal values for RVEDVI were 100
ml/m2 in males and 92 ml/m2 in females. Their respective
references for RVESVI were 53 ml/m2 and 51 ml/m2. Their
lower limits for RVEF; 30% in males and 38% in females;
are, however, comparable to our data. The
underestimation of RV volumes in our study may therefore have been
of a similar magnitude in end-diastole and end-systole,
resulting in meaningful RVEF measurements.
RT3DE using off-line analyses with dedicated software
(e.g. Tomtec) seem to underestimate RV volumes to a less
extent compared with cardiac magnetic resonance (CMR)
than the methodology used in our study [10,11].
In Kjaergaard et al's.  study of 54 healthy volunteers
upper normal RVEDVI was 88 ml/m2 in males and 80 ml/
m2 in females. The respective limits for RVESVI were 46
ml/m2 and 38 ml/m2. There was a tendency for smaller
volumes to be associated with increasing age. The lower
references for RV volumes may be related to differences in
methodology, since Kjaergaard et al. used disk
CMR is regarded as the best measure of cardiac
dimensions. In Gopal et al's. study , CMR derived max
RVEDVI was 97 ml/m2, max RVEDVI 53 ml/m2 and min
RVEF 35%. These values are quite similar to their RT3DE
derived references. Maceira et al.  studied 120 healthy
volunteers comprising of 10 females and 10 males with
CMR in each decade between 20 and 80 years. Their upper
normal values were 100 ml/m2 for RVEDVI and 41 ml/m2
for RVESVI, whilst the lower limit for RVEF was 54%. BSA
corrected RV volumes were larger in males and a
significant negative correlation between age and RV volumes
was found. RVEF did not differ between genders but was
positively correlated with age.
Hudsmith et al.  studied 108 healthy volunteers with
CMR aged between 21 and 68 years. Upper normal values
were 123 ml/m2 for RVEDVI and 56 ml/m2 for RVESVI,
whilst lower normal RVEF was 49%. BSA corrected RV
volumes were larger in males than females and tended to be
smaller in participants aged >35 years.
Within these studies there are considerable inter- and
intra- methodological discrepancies between upper
reference values for RV volumes, despite the fact that all
measurements claim to have included both RV inflow and
outflow tracts. Especially concerning is the large
discrepancy between the lower normal limit for RVEF when
derived from RT3DE as opposed to CMR. All studies,
including ours, emphasize the need for gender-specific
reference values corrected for BSA. The data supporting
age-related corrections are not convincing. The
correlations between age and RV volumes in our study were so
weak that such a correction is not deemed to be necessary.
Our 2DE results also emphasise the need to use reference
values for RV areas corrected for age and BSA. The normal
ranges presented in the ASE/EAS guidelines are obtained
from a group of 72 adult patients aged from 15 to 76
(mean 38) years with a mean BSA of 1.75 (range 1.4 2.1)
m2 . For RV areas, however, only 41 participants were
included. BSA corrected reference values are not
presented. Max RVAEDI (mean +2SD) was 24 cm2 and max
RVAESI 17 cm2, whereas minimum RVAF (mean -2SD)
was 31%. In our study the respective values were 31 cm2,
18 cm2 and 27%. Since the measurement techniques were
quite similar, the discrepancies between the upper normal
diastolic areas and RV AF may be related to the differences
in the study populations. These differences might have
been smaller if BSA corrected values had been available as
in Weyman et al's. study .
The blinded reproducibility study indicates unacceptable
intraobserver variability with both methods. To optimize
reproducibility the unblinded approach should be
introduced into routine clinical practice. The intraobserver
variability of 2DE derived areas was slightly better than that
of RT3DE derived volumes in the unblinded study. In
addition, the interobserver variability for the 2DE method
was of clinical importance, emphasizing the need for
repeated unblinded measurements performed by the
same investigator during follow-up examinations of RV
dimensions. Due to anticipated learning curve problems,
we chose to use only one experienced investigator to
perform the RT3DE recordings and measurements.
With the shortcomings of the present RT3DE technique
and the limitations of this study in mind, it seems
apparent that single plane 2D-derived RV areas and AF is still
the preferred method for assessment of systolic RV
function. In adult cardiology, patients eligible for such
assessment are those with congenital disorders, acute and
chronic pulmonary disease, RV infarction, valvular
disease and heart failure. RVAF has been shown to be an
important prognostic factor in patients with left
ventricular dysfunction after acute myocardial infarction  and
in patients with severe left ventricular systolic dysfunction
after coronary artery bypass grafting . Whether RT3DE
measurements as performed in the present study will
provide additional information remains to be proven in
Given that the age distribution of participants was not as
wide as we had aimed for it cannot be ruled out that the
age-related correlations presented might have been
stronger with a wider age range. It must be stressed that
the normal reference data set presented with both
methods reflect the RV inflow tract, since inclusion of the RV
outflow tract was not possible with the apical approach
and methods applied. Due to the importance placed upon
examiner experience with this new method we have not
provided interobserver variability for RT3DE derived
volumes. Due to imitated capacity in our CMR-laboratory, it
was not possible to obtain RV volumes with that method
RT3DE with automatic border detection and fast online
analysis is hampered by the underestimation of RV
volumes when compared with MRI and RT3DE with offline
analysis. The RVEF data presented may be more realistic
for RV function since the error in volume determination
may be equally pronounced in ED and ES. The serial
reproducibility is only acceptable if previous recordings
and tracings are available. 2DE measurements of RV areas
and AF are simple to perform and are fairly accurate and
reproducible provided the unblinded approach is
practiced. Both methods are suitable as a bedside tool for
immediate clinical decisions. The present study has
expanded the knowledge of normal RV dimensions and
contractility obtained with apical RT3DE and 2DE
recordings from a large series of individuals, allowing the
presentation of BSA and gender corrected values.
The authors declare that they have no competing interests.
EA participated in the design of the study, performed
echocardiographic examinations, did all statistical
analyses and drafted the manuscript. MB performed
echocardiographic examinations and critically revised the
manuscript for important intellectual content. OR
participated in interpretation of the data and critically revised
the manuscript. JEO participated in the design of the
study, performed echocardiographic examinations and
drafted the manuscript. All authors read and approved the
The authors are grateful to the study secretaries; Hege Bjoerndahl and
Merete Bellsund; for their efforts throughout this study. This study was
supported by a research grant from the South-Eastern Norway Regional
1. Helbing WA : Right ventricular function: the comeback of echocardiography ? Eur J Echocardiogr 2004 , 5 : 99 - 101 .
2. Burgess MI , Bright-Thomas RJ , Ray SG : Echocardiographic evaluation of right ventricular function . Eur J Echocardiogr 2002 , 3 : 252 - 62 .
3. Watanabe T , Katsume H , Matsukubo H , Furukawa K , Ijichi H : Estimation of right ventricular volume with two dimensional echocardiography . Am J Cardiol 1982 , 49 : 1946 - 53 .
4. Levine RA , Gibson TC , Aretz T , Gillam LD , Guyer DE , King ME , Weyman AE : Echocardiographic measurement of right ventricular volume . Circulation 1984 , 69 : 497 - 505 .
5. Lang RM , Bierig M , Devereux RB , Flachskampf FA , Foster E , Pellikka PA , Picard MH , Roman MJ , Seward J , Shanewise JS , Solomon SD , Spencer KT , Sutton MS , Stewart WJ : Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology . J Am Soc Echocardiogr 2005 , 18 : 1440 - 63 .
6. Gopal AS , Chukwu EO , Iwuchukwu CJ , Katz AS , Toole RS , Schapiro W , Reichek N : Normal values of right ventricular size and function by real-time 3-dimensional echocardiography: comparison with cardiac magnetic resonance imaging . J Am Soc Echocardiogr 2007 , 20 : 445 - 55 .
7. Dubois D , Dubois EF : Clinical calorimetry. A formula to estimate the approximate surface area if height and weight are known . Arch Int Med 1916 , 17 : 863 - 71 .
8. Jacobs LD , Salgo IS , Goonewardena S , Weinert L , Coon P , Bardo D , Gerard O , Allain P , Zamorano JL , de Isla LP , Mor-Avi V , Lang RM : Rapid online quantification of left ventricular volume from real-time three-dimensional echocardiographic data . Eur Heart J 2006 , 27 : 460 - 8 .
9. Maceira AM , Prasad SK , Khan M , Pennell DJ : Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance . Eur Heart J 2006 , 27 : 2879 - 88 .
10. Jenkins C , Chan J , Bricknell K , Strudwick M , Marwick TH : Reproducibility of right ventricular volumes and ejection fraction using real-time three-dimensional echocardiography: comparison with cardiac MRI . Chest 2007 , 131 : 1844 - 51 .
11. Kjaergaard J , Petersen CL , Kjaer A , Schaadt BK , Oh JK , Hassager C : Evaluation of right ventricular volume and function by 2D and 3D echocardiography compared to MRI . Eur J Echocardiogr 2006 , 7 : 430 - 8 .
12. Kjaergaard J , Sogaard P , Hassager C : Quantitative echocardiographic analysis of the right ventricle in healthy individuals . J Am Soc Echocardiogr 2006 , 19 : 1365 - 72 .
13. Hudsmith LE , Petersen SE , Francis JM , Robson MD , Neubauer S : Normal human left and right ventricular and left atrial dimensions using steady state free precession magnetic resonance imaging . J Cardiovasc Magn Reson 2005 , 7 : 775 - 82 .
14. Weyman A : Practices and principles of echocardiography 2nd edition . Philadelphia: Lippincott, Williams and Wilkins; 1994 .
15. Zornoff LA , Skali H , Pfeffer MA , St John SM , Rouleau JL , Lamas GA , Plappert T , Rouleau JR , Moye LA , Lewis SJ , Braunwald E , Solomon SD : Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction . J Am Coll Cardiol 2002 , 39 : 1450 - 5 .
16. Maslow AD , Regan MM , Panzica P , Heindel S , Mashikian J , Comunale ME : Precardiopulmonary bypass right ventricular function is associated with poor outcome after coronary artery bypass grafting in patients with severe left ventricular systolic dysfunction . Anesth Analg 2002 , 95 : 1507 - 18 .