Download Reference Values for and Determinants of Right Atrial Area in

Reference Values for and Determinants of Right Atrial Area
in Healthy Adults by 2-Dimensional Echocardiography
Ekkehard Grünig, MD*; Philipp Henn*; Antonello D’Andrea, MD*; Martin Claussen, MD;
Nicola Ehlken, BSc; Felicitas Maier; Robert Naeije, MD, PhD; Christian Nagel, MD; Felix Prange;
Johannes Weidenhammer; Christine Fischer, PhD*; Eduardo Bossone, MD*
Background—Right atrial (RA) size is important in screening, diagnosis, and follow-up assessment in patients with pulmonary
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
hypertension. The objective of this study was to define normal reference values for RA area by echocardiography in a large
population of athletic versus sedentary healthy subjects.
Methods and Results—In the first part of the study, 880 healthy adult subjects (mean age, 28±6 years; 38% women; 395 top-level
endurance athletes, 255 strength athletes, and 230 nonathletes) were prospectively assessed. In the second part, we performed a
pooled analysis of all studies published between 1976 and 2011 describing RA area in healthy subjects (n=624). Statistical analysis
included the calculation of 95% quantiles for defining cutoff values. Mean RA area in the 880 subjects was significantly larger
in endurance athletes compared with the strength athletes and nonathletes. RA area correlated significantly with age, sex, body
surface, and endurance training. In a synopsis of both data sets, 95% quantiles for RA area in strength atheletes and nonathletes
were 15.2 cm2 (95% confidence interval, 14.7–15.7) in women and 16.2 cm2 (95% confidence interval, 15.8–16.6) in men.
Conclusions—To the best of our knowledge, this is the largest data set to describe RA size in adult healthy subjects (age <50
years). Cutoff values for RA area were significantly different in women (15 cm2) and men (16 cm2). Age, sex, body surface area,
and high-level endurance training were determinants of RA area. (Circ Cardiovasc Imaging. 2013;6:117-124.)
Key Words: echocardiography ◼ pulmonary hypertension ◼ reference values ◼ right atrium ◼ risk factors
R
ight atrial (RA) size is of clinical importance because it
reflects right ventricular (RV) function and is strongly
associated with clinical outcomes in many conditions such
as pulmonary hypertension.1–3 The normal RA is a thin, oval
structure influencing RV function as a passive conduit to the
RV in early diastole. When the tricuspid valve is open, it acts
as a reservoir for systemic venous return and fills the RV by
active contraction during late diastole.4 RA contraction is
responsible for up to 30% of normal RV output.5 In healthy
subjects, short elevations of RV pressure lead to stretching
and enlargement of the RA, resulting in more reservoir volume. This mechanism has been identified to compensate for
short-term RV overload.6 Chronic pulmonary hypertension
is followed by enlargement and remodeling of the RA with
hypertrophy and reduced contractility.7,8
assessments in several diseases affecting the right side of the
heart such as cardiomyopathy and pulmonary hypertension.9–11
For echocardiographic evaluation of the RA size, the RA area
is easy to obtain and seems to be more reliable assessing RA
diameters or volume.11,12 Volumetric quantification of the right
atrium is challenging because many assumptions are required11
and it is more difficult to perform in the daily clinical practice.
However, there are limited data on the normal size of the RV and
RA.3,11,13 Furthermore, echocardiographic views required for
optimal evaluation of the right heart are less well standardized,
leading to inconsistent measurements of RV and RA size. The
reference value given for mean RA area in the recommendations
of the American Society of Echocardiography of 18 cm2 is not
sex specific and is based on few studies including only 293
healthy subjects. Therefore, the authors of the current American
guidelines for echocardiography stated that their text has to
be viewed as an incentive to refine the normal values of the
right heart.11 Today, there are no reference values given for RA
area/size indexed for body surface area (BSA), age, physical
training status, or sex in any guidelines.11
Clinical Perspective on p 124
Echocardiography has become the most clinically relevant
noninvasive diagnostic technique evaluating the right heart.9
It can be used for screening, diagnosis, and follow-up
Received June 19, 2012; accepted November 15, 2012.
From the Centre for Pulmonary Hypertension at Thoraxclinic Heidelberg, Heidelberg, Germany (E.G., P.H., N.E., F.M., C.N., F.P., J.W.); Second
University of Naples, Monaldi Hospital, Naples, Italy (A.D.); Department of Pneumology, Clinic Grosshansdorf, Grosshansdorf, Germany (M.C.);
Erasme University Hospital Free University of Brussels, Brussels, Belgium (R.N.); Department of Human Genetics, University of Heidelberg, Heidelberg,
Germany (C.F.); and Cardiology Division, “Cava de’ Tirreni and Amalfi Coast” Hospital, Heart Department, University of Salerno–Italy, and Cardiac
Surgery Department, IRCCS Policlinico San Donato, Milan, Italy (E.B.).
*Drs Grunig, Henn, and D’Andrea contributed equally to this work.
Correspondence to Ekkehard Grünig, MD, Centre for Pulmonary Hypertension Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, 69126
Heidelberg, Germany. E-mail [email protected]
© 2012 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
117
DOI: 10.1161/CIRCIMAGING.112.978031
118 Circ Cardiovasc Imaging January 2013
The aim of this study was to analyze the dimensions of RA area
first in a large prospectively assessed population of healthy adults
and second in a pooled analysis of all previously reported studies,
including those that have not been taken into account in the current
guidelines. Thus, we aimed to confirm reference values for RA
area using prospectively obtained data and analyzing previously
reported data. Furthermore, we wanted to identify determinants of
RA size such as sex, age, BSA, and exercise training status.
Methods
Study Population
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
From June 2008 to March 2009, 880 healthy athletic and nonathletic
subjects were prospectively and consecutively studied by 2-dimensional echocardiography at Monaldi Hospital, Naples, Italy, as previously
described.14 The athletes were employed by professional sports associations and had been trained intensively 15 to 20 h/wk for >4 years. The
subjects were referred for cardiovascular preparticipation screening.
Volunteer control subjects were all recruited in Naples (Italy), selected
from the Department of Cardiology, and investigated for work eligibility. None of the control subjects had cardiovascular structural or functional abnormalities or received any medication. All subjects underwent
a detailed history, physical examination, BSA, ECG, chest radiography, exercise test, and comprehensive transthoracic echocardiography,
including Doppler studies, as described previously.14 Subjects with
cardiopulmonary diseases such as coronary artery disease, systemic arterial hypertension, valvular or congenital heart disease, bicuspid aortic
valve, congestive heart failure, cardiomyopathies, and diabetes mellitus
were excluded. Additional exclusion criteria were sinus tachycardia and
inadequate echocardiographic image quality. Use of anabolic steroids
or other illicit drugs was ruled out by medical history and patient interview. According to these criteria, 10 subjects were excluded (3 for
bicuspid aortic valve, 1 for hypertrophic cardiomyopathy, 4 for use of
anabolic steroids, and 2 for inadequate echocardiographic image quality). The final study population consisted of 880 subjects. Although results for healthy nonathletes have not been analyzed yet, some data on
the function of the right side of the heart in athletes have been reported
previously.14 The study was approved by the local Ethics Committee.
All subjects enrolled in the study gave informed consent.
Echocardiographic Assessment
Doppler and 2-dimen­sional echocardiographic recordings were performed with 2.5-MHz Duplex probes and conventional equipment
(Vivid 7, GE Healthcare, Milwaukee, WI) by experienced cardiac sonographers. RA measurements were assessed in the apical 4-chamber
view. RA area was estimated by planimetry at the end of ventricular
systole (largest volume), tracing from the lateral aspect of the tricuspid annulus to the septal aspect, excluding the area between the
leaflets and annulus, after the RA endocardium (Figure 1). All studies were reviewed and analyzed offline by 2 independent observers
blinded to the clinical characteristics of the study population. As an
example, Figure 1 shows a normal and an enlarged RA area measured
by echocardiography and describes the technique. For exclusion of
pulmonary hypertension or any heart diseases possibly affecting the
size of the right side of the heart such as congenital heart defects,
a complete echocardiographic assessment, including assessment of
pulmonary artery pressures, was performed in all subjects.15 For all
calculations, the mean value from at least 3 to 5 measurements was
used. RA pressure was estimated from characteristics of the inferior
vena cava.16 Patients with suspected heart diseases or elevated pulmonary systolic artery pressures (>35 mm Hg) and elevated estimated
RA pressure (diameter of inferior vena cava >20 mm) were excluded.
Figure 1. Echocardiographic measurement of the right atrial
(RA) area in the apical 4-chamber view. The figure shows schematically and echocardiographically how RA area measurements
have been performed in the apical 4-chamber view. Left, The RA
area is of normal size. Right, An enlarged RA area in a patient
with pulmonary arterial hypertension.
reference values in humans. Our approach was to search by Medical
Subheadings or key words related to RA size, diameters, volume, and
area. In addition, reference lists of relevant studies, practice guidelines, and reviews were screened to identify further studies not detected by the electronic search. All studies in English, German, and
Italian were screened. We selected studies that described RA size/
area in healthy adults without cardiovascular diseases using standardized echocardiographic views. We excluded studies with unclear
echocardiographic techniques or status of subjects.
Statistical Methods
All analyses were performed by a statistician (C.F.).
Determination of RA Area and RA Area Indexed for BSA
In the prospective analysis, all reported values of RA area represent the mean of at least 3 measurements. To calculate RA
area indexed for BSA in the prospective study, we used the following formula: RA area indexed for BSA (cm2/m2)=RA area
absolute (cm2)/BSA (m2) for each individual measurement.
BSA was calculated using this formula: BSA=weight (kg)
0.425×height (cm)×71.84×10–4.17 If only RA area absolute or
RA area indexed was given in the literature, we calculated the
other value using the mean BSA if possible (see Table 1).
Literature Search
Prospective Analysis
RA areas are presented as means and standard deviations. As
upper cutoff values for normal RA areas for women and men,
we used 95% quantiles and their 95% confidence intervals
(CIs). The values were calculated with and without assuming a
normal distribution using SAS version 9.2 (SAS Institute Inc,
Cary, NC). The calculation assuming nonnormally distributed
values led to nearly identical quantiles and CIs; therefore, we
present the results assuming normality. The comparison of
95% quantiles between men and women and between groups
with different exercise training status was performed with the
SAS QUANTREG procedure.
We performed a systematic literature search using Medline and the
Cochrane Database for studies published between January 1966
and October 2011 reporting echocardiographic RA measurements
in healthy subjects. This encompassed studies reporting normal
Analysis of Determinants
We calculated correlation coefficients to describe determinants of RA area. Additionally, groups with different exercise
Grünig et al Reference Values of Right Atrial Area 119
Table 1. Characteristics of Pooled Analysis of Selected Studies on Right Atrial Area by 2-Dimensional Echocardiography
Author
Year
n
Retrospective
Study Design
Ref. 22
1979
25
X
44
Ref. 23
1983
11
X
27
X
Ref. 19
1984
30
?
50
X
Ref. 12
1984
67
?
?
Ref. 20
1984
54
Ref. 18
1986
43
Ref. 21
2007
160
Ref. 24
2009
15
Ref. 25
2010
219
Sum
Women,
%
46.3
?
BSA
Sex
Distinction
X
Index
Athletes
Nonathletes
Men
X
45
X
X
X
22–37
X
X
31±10
X
38
X
38.4
X
X
X
51.2
X
X
37.5
X
X
54.3
Abs.
Mean Age, y
X
53
X
Area
X
X
X
X
X
X
X
Women
28±8
37.6
X
40±14
36±14
X
24.9±4.4
22.2±4.5
X
X
36±12
X
X
29.7±25.2
624
Abs. indicates absolute; and BSA, body surface area.
Studies are listed in chronologic order of publication year.
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
training status (ie, endurance-exercise training, strength-exercise training, or nonathletes) and sex groups were compared
by ANOVA. Multivariate regression analysis was performed
to take age, BSA, and sex into account simultaneously. Values
of P<0.05 were considered statistically significant. For these
analyses, we used IBM SPSS 20 (SPSS Statistics version 20,
IBM Corp, Somers, NY).
Literature Analysis
Because only aggregated data, namely means, standard deviations, and sample sizes, are given in the literature, we estimated the 95% percentile assuming normally distributed data.
Additionally, 95% CIs for the 95% percentile were determined
by using the 97.5% CIs of the estimated mean and standard
deviation of each single study. We combined the results from
the literature with our data by pooling means and standard
deviations for each study weighted by sample size, assuming
a common underlying normal distribution. From the pooled
mean and the pooled standard deviation, the 95% percentiles
and their 95% CIs were estimated as described above.
To analyze the influence of single studies on the pooled estimate, a sensitivity analysis was performed by leaving out 1 study
at a time and calculating the pooled estimates with the remaining
studies. All these analyses were performed with tailored software.
Results
RA Area Prospectively Obtained in Healthy
Athletes/Nonathletes
We prospectively assessed 880 healthy adults: 230 nonathletes, 255
strength athletes, and 395 endurance athletes (Table 1 and Figures
2 and 3). Mean age was 28.2±10.5 years (range, 18–45 years) and
did not differ significantly between groups. The mean absolute and
indexed RA area values with standard deviations, the 95% quantiles, and the range of CIs are shown in Table 1. The 95% quantiles
that have been defined as cutoff values for normal RA area were
almost identical in nonathletes and strength athletes. In nonathletes,
the 95% quantiles were significantly different between men and
women (P=0.0042): 15.1 cm2 (CI, 14.3–16.0) in women, 15.7 cm2
(CI, 15.1–16.5) in men, and 15.5 cm2 (CI, 15.1–15.9) in the mixedsex group (Table 1). RA area indexed for BSA in nonathletes was
8.2 cm2/m2 in women, 8.4 cm2/m2 in men, and 8.3 cm2/m2 in the
mixed-sex group (Table 1).
Correlation Analysis of RA Area With Age, Sex,
BSA, and Exercise Training Status
RA area means were significantly different among nonathletes
(12.5±2.0 cm2), strength athletes (12.7±1.6 cm2), and endurance
athletes (15.4±2.1 cm2; P<0.0001, ANOVA; Figure 2A) and
Figure 2. Determinants of right atrial
(RA) area. A, Type of training. B, Sex.
A, Whisker plot illustrating the effect of
endurance and strength training on RA
area, prospectively evaluated. Endurance
athletes had significantly larger RA areas
compared with nonathletes and strength
athletes. B, Significantly different RA area
sizes in male and female nonathletes. The
boxes represent the values of all subjects
between the 25% and 75% quantiles
(median line; the range from 5% to 95%
quantiles is shown by the whiskers.
120 Circ Cardiovasc Imaging January 2013
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
between men and women of the nonathletic group (P=0.0042;
Figure 2B). If sex, age, BSA, and training status were taken
into account simultaneously, only the correlations of RA
area with endurance training and BSA, but not sex, remained
significant. There was a significant but weak correlation of RA
area with age (r=0.17, P<0.0001) and BSA (r=0.33, P<0.0001)
in nonathletes and strength athletes (n=485). In endurance
athletes (n=395), a weak correlation between RA area and age
(r=0.23, P<0.001) and between RA area and BSA (r=0.29,
P<0.001) occurred. Only 3% of the variability of RA area
could be explained by age; 11% could be explained by BSA.
The different RA areas in men and women were confirmed
in the pooled analysis of those previously published studies
that distinguished between sexes. In all of these studies,18,19,21
we found significantly different mean RA areas in men and
women, ranging from 2.6 to 3.0 cm2. In publications selected
for the pooled analysis, we could not perform further correlation analysis concerning age, training status, and BSA or any
other variables because only mean values for RA area were
given and no analysis for determinants had been reported.
RA Area Obtained by Pooled Analysis of Previously
Published Studies
Eleven studies were detected by screening of Medline databases and Cochrane databases for RA size. Two of the 11 studies were excluded.2,26 The second oldest of the 11 studies from
Reeves et al26 identified a mean value of RA area of 16.1±3.4
cm2 in a mixed-sex cohort of 21 healthy control subjects.
However, they used a sector-scan echocardiography Picker
80-C cardiac imager that was technically limited; echocardiographic 4-chamber views were different.26 The data of Raymond et al2 were not included because the RA area index was
calculated from height instead of BSA. Therefore, because no
mean height was provided, we were unable to calculate the
absolute or indexed values for RA area.
Thus, 9 studies published between 1979 and 2011 with
624 healthy subjects were used for the pooled analysis
(Table 2). The assessed subjects had been classified as healthy
and free of heart disease in all studies. As far as specified,
most studies had performed ECGs and physical examinations
to exclude any heart disease. In 1 study, catheterization of
the right and left sides of the heart had been performed.26 In
addition, in this study, rubber casts fashioned from the rightside chambers during necropsy had been assessed in 8 deceased
subjects without clinical or anatomic evidence of heart–lung
diseases to validate the echocardiographic dimensions of the
heart chambers.22 Overall, the assessed subjects were between
18 and 70 years; the mean age ranged between 22.2±4.5
years21 and 45 years22 (Table 2). Most subjects were <50 years
of age. The sample size ranged from 11 to 219 subjects per
study. The percentage of women ranged from 27% to 54.3%,
although 1 study did not mention sex distribution (Table 2).
Three studies were retrospective in design; in 3 others, the
study design was not completely clear; 5 studies12,18–20 were
designed for reference value determination; and 4 studies21–25
used healthy subjects as the control group.
Table 3 summarizes the mean values for absolute and
indexed RA area, standard deviations, 95% quantiles, and
Table 2. Right Atrial Area Prospectively Obtained in 880 Healthy Subjects
Sex
Nonathletes
Strength
Athletes
Endurance Athletes
No. (%)
Men
Women
137 (15.6%)
155 (17.6%)
255 (29.0%)
93 (10.6%)
100 (11.4%)
140 (15.9%)
RA area, cm2
Men
Mean±SD
12.5±2.0
12.7±1.6
15.4±2.1
Q-95 (CI)
15.7 (15.1–16.5)
15.3 (14.8–15.9)
19.5 (19.0–20.0)
Mean±SD
11.9±1.9
12.8±1.5
15.3±2.1
Q-95 (CI)
15.1 (14.3–16.0)
15.3 (14.7–16.0)
19.5 (18.5–20.5)
15.5 (15.1–15.9)
15.5 (15.0–15.6)
19.5 (19.0–20.0)
Women
Mixed
Q-95 (CI)
RA area index, cm /m
2
2
Men
Mean±SD
6.7±1.0
6.9±0.9
8.3±1.1
Q-95 (CI)
8.4 (8.1–8.8)
8.3 (8.0–8.6)
10.4 (10.1–11.0)
Women
Mean±SD
6.5±1.0
7.0±0.8
8.2±1.1
Q-95 (CI)
8.2 (7.7–8.6)
8.3 (8.0–8.6)
10.4 (9.9–11.1)
8.3 (8.1–8.5)
8.2 (8.1–8.5)
10.4 (10.1–10.7)
Mixed
Q-95 (CI)
CI indicates confidence interval; Q-95, 95% quantile; and RA, right atrial.
Grünig et al Reference Values of Right Atrial Area 121
Table 3. Mean Absolute and for Body Surface Area-Indexed Right Atrial Area: Pooled Values of Our Analysis and for Pooled
Analysis of Selected Studies
RA Area, cm2
n
Mean±SD
Q-95
RA Area Index, cm2/m2
Q-95 (L-CI/U-CI)
n
Mean
Q-95
Q-95 (L-CI/U-CI)
Men
Nonathletes
378
13.0±1.9
16.2
15.8–16.6
378
7.0±0.9
8.6
8.4–8.8
Ref. 19
Nonathletes
15
13.6±4.7
21.3
16.9–28.2
15
7.1±1.1
8.9
7.9–10.5
Ref. 18
Nonathletes
21
14.0±2.3
17.7
15.9–20.3
21
7.4±1.2
9.4
8.4–10.8
Ref. 21
Nonathletes
50
14.9±1.7
17.7
16.8–18.9
50
8.1±1.0
9.7
9.2–10.4
This study
Nonathletes
137
12.5±2.0
15.7
15.1–16.5
137
6.7±1.0
8.4
8.1–8.8
This study
Strength
155
12.7±1.6
15.3
14.8–15.9
155
6.9±0.8
8.3
8.0–8.6
Men
Endurance
This study
Endurance
255
15.4±2.1
18.9
18.4–19.5
255
8.3±1.1
10.1
9.8–10.4
Ref. 21
Endurance
50
21.2±4.0
27.8
25.6–30.5
50
10.8±0.9
13.9
12.9–15.2
Women
Nonathletes
260
12.2±1.8
15.2
14.7–15.7
260
6.9±1.0
8.5
8.3–8.8
Ref. 19
Nonathletes
15
10.6±2.8
15.2
12.6–19.3
15
6.6±0.9
8.1
7.2–9.4
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
Ref. 18
Nonathletes
22
11.4±1.6
14.0
12.8–15.9
22
7.0±1.0
8.6
7.8–9.8
Ref. 21
Nonathletes
30
12.2±2.4
16.1
14.5–18.4
30
7.5±1.6
10.1
9.0–11.6
This study
Nonathletes
This study
Strength
Women
Endurance
93
11.9±1.9
15.1
14.3–16.0
93
6.5±1.0
8.2
7.7–8.6
100
12.8±1.5
15.3
14.7–16.0
100
7.0±0.8
8.3
8.0–8.6
This study
Endurance
140
15.3±2.1
18.7
18.0–19.5
140
8.2±1.1
10.0
9.6–10.4
Ref. 21
Endurance
30
16.1±3.6
22.0
19.5–25.3
30
9.4±2.2
13.0
11.5–15.1
Mixed sex
Nonathletes
1012
12.6±3.0
17.5
17.1–17.9
987
7.1±1.8
10.1
9.9–10.4
14.5–15.8
Ref. 22
Nonathletes
25
13.9±0.7
15.1
Ref. 23
Nonathletes
11
7.1±0.6
8.0
7.4–9.1
11
4.0±0.3
4.5
4.2–5.1
Ref. 12
Nonathletes
67
13.5±2.0
16.8
15.8–17.9
67
7.7±1.1
9.6
9.0–10.3
Ref. 20
Nonathletes
48
13.0±3.0
17.9
16.3–20.0
48
7.1±1.6
9.8
8.9–10.9
Ref. 24
Nonathletes
15
15.0±7.0
26.5
19.9–36.7
15
8.3±3.9
14.7
11.0–20.4
Ref. 25
Nonathletes
219
11.5±5.0
19.7
18.4–21.2
219
7.4±3.2
12.6
11.8–13.6
BSA indicates body surface area; L-CI/U-CI, lower and upper 95% confidence interval; Q-95, 95% quantile; and RA, right atrial.
RA analysis for pooled values does not include endurance athletes.
their 95% CIs for all studies used in the pooled analysis
and for our study population. Furthermore, in each of the
identified studies, RA values obtained in the subgroups
based on sex and training status are shown. The mean absolute RA area ranged from 4 cm2 (which we considered
implausible, so we excluded the values from further calculation)23 to 6.6 cm19 in female nonathletes to 21.2 cm21 in
male endurance athletes. In each study, values for the 95%
quantiles and CIs were calculated and compared with the
values we obtained in our study population in 880 healthy
subjects.14
Pooled Values for RA Area Derived From 10
Studies: Pooled Analysis of Previous Data and
Prospectively Assessed Healthy Subjects
In the heading lines (grey indicated) of Table 3, mean values are
given for 378 men, 260 women, and 1012 unknown-sex nonathletes and strength athletes and 305 male and 170 female endurance athletes. We included nonathletes and strength athletes in
the normal group because their RA distributions are very similar. The means were derived from values of the 9 studies of the
pooled analysis and our own prospective data of 880 healthy
subjects. Figure 3 illustrates the 95% quantiles and CIs of RA
area assigned to the analyzed studies and subgroups. Overall,
in strength/nonstrength athletes, the pooled mean RA area was
12.2±1.8 cm2 in women, 13.0±1.9 cm2 in men, and 12.6±3.0
cm2 in the mixed-sex group (Table 3). Pooled 95% quantiles of
RA area were 15.2 cm2 in women, 16.2 cm2 in men, and 17.5
cm2 in mixed sex group (Table 3 and Figure 3). Pooled 95%
quantiles of RA areas indexed for BSA were 8.5 cm2/m2 (8.3–
8.8 cm2/m2) in women, 8.6 cm2/m2 (8.4–8.8 cm2/m2) in men,
and 10.1 cm2/m2 (9.9–10.4 cm2/m2) in the mixed-sex group.
Sensitivity Analysis
Without our prospectively obtained data, the reference values
for the mixed-sex group were slightly higher, and without the
values from Kelly et al,25 they were slightly lower (16.7 cm2).
For women, no study had a remarkable influence. The leaveone-out estimates for the reference values for men varied
between 15.9 and 18.3 cm2.
Discussion
To the best of our knowledge, this is the largest data set on
RA size in healthy adults (n=880 our study population, n=624
pooled analysis) between 18 and 70 years of age (most of them
122 Circ Cardiovasc Imaging January 2013
Figure 3. Mean values of echocardiographically
measured right atrial (RA) area in our data and a
pooled analysis of selected previous studies. The
figure presents the 95% quantile of the RA area and
the range of 95% confidence intervals of our prospective data and previous publications selected
for pooled analysis. The values are given for men
and women with different training status. Bottom,
The pooled values.
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
<50 years of age) up to now. The calculated reference values
for RA size obtained by 2-dimensional echocardiography in
the apical 4-chamber view are based on almost all prospective
and retrospective studies published so far. This is the first study
to provide normal reference values for RA area. The study
confirms that absolute cutoff values should be determined and
used sex-specifically. Absolute cutoff values for RA area in
nonathletes/strength athletes were significantly different in
women (15 cm2) and men (16 cm2), whereas values indexed
for BSA were similar in both sexes (women, 8.5 cm2/m2;
men, 8.6 cm2/m2). Age, sex, BSA, and high-level endurance
exercise training were identified as determinants of RA area.
Top-level endurance athletes exceeded the reference values of
RA area for nonathletes and strength athletes and showed no
significant differences between men and women.
RA size evaluated by 2-dimen­
sional echocardiography correlated well with rubber casts of heart chambers
obtained at autopsy,22 with hemodynamic measurements,
and with assessment by magnetic resonance imaging.27
The absolute RA area obtained by echocardiography in the
apical 4-chamber view is a reliable and, in most subjects,
accurately measurable parameter. It can be obtained even
by older echocardiography devices and is of major clinical relevance. This parameter reflects RV function5,8 and is
important for follow-up assessment and risk stratification
in patients with right-sided heart failure such as patients
with pulmonary hypertension.9,10 Furthermore, enlarged
RA area belongs to the echocardiographic parameters that
might raise or reinforce suspicion of pulmonary hypertension independently of tricuspid regurgitation velocity9,10
and may be an early indicator for primary diseases of
the right side of the heart. RA area distinguished healthy
subjects from patients with RV volume overload or rightsided heart diseases with only minimal overlap between the
groups,8,22,23,25 as long as correct cutoff values were used.
Furthermore, an enlarged atrium may be an early indicator of pulmonary hypertension and primary diseases of the
right side of the heart.
For clinical practice, it is more convenient to measure the
absolute area instead of performing the corrections for BSA.
Therefore, the finding that women and men have significantly
different absolute RA areas is of clinical importance and has
already been observed in small cohorts of healthy subjects.18–20
Nevertheless, sex differences in RA size have not been analyzed systematically so far and have not led to different sexspecific reference values.11 This study confirms for the first
time sex differences and the influence of age, BSA, and training status on echocardiographic RA area in a large number
of healthy adult subjects. Mixed-sex values for absolute RA
area11 should therefore not be used any longer to avoid the risk
of underestimation of RA enlargement, especially in women.
However, no significant sex differences were observed
when RA area was corrected for BSA and training status
(endurance athletes). Different reference values for men and
women have also been documented for echocardiographic RV
end-diastolic area.28
Absolute RA area was significantly, but weakly, correlated with age. Older subjects had slightly enlarged RA areas.
However, most subjects of this study were <50 years of age.
In this cohort, age accounted for only 3% of the variance of
values. According to the results of the prospective study and
the pooled analysis of all previous studies, there is no need to
adapt the reference values of 15 cm2 for women and 16 cm2 for
men to age. Nevertheless, further evaluation of children and
healthy subjects >50 years of age is necessary to determine
normal RA area in these groups.
Numerous studies have described “athlete’s heart
syndrome” with chamber enlargement of the left and right
sides of the heart.29 However, the effect on RA size is less well
evaluated. Acute, transient RA and RV dilatation, reduction of
Grünig et al Reference Values of Right Atrial Area 123
RV ejection fraction obtained by magnetic resonance imaging,
and release of B-type natriuretic peptides30 and cardiac
troponin I31 were seen immediately after severe endurance
exercise such as marathon running. Ector et al32 proposed that
the right ventricle may be more severely affected by endurance
training because of its thin-walled structure compared with the
left ventricle. Larger RA size compared with that of sedentary
control subjects by 2-dimensional echocardiography was
also described in professional tennis players participating at
the French Open.21 In our study, endurance-trained top-level
athletes had substantially larger RA areas with a 95% quantile
of 19.5 cm2 compared with that measured in nonathletes and
strength athletes. A possible explanation for this might be that
endurance training leads to higher volume loads of the RV,29,33
whereas strength athletes generate higher pressures with only
transiently increased volume loads.29,33
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
Limitations
The studies included in the pooled analysis had different definitions of “healthy participants.” Right-sided and left-sided heart
catheterization was performed in only 1 study.22 Some other
studies were retrospective in design, and not all studies aimed
to determine reference values, so we cannot exclude a referral
bias. These studies caused a larger standard deviation of mean
RA areas that is also reflected in the larger 95% percentile for
the mixed-sex group in the pooled analysis compared with the
values obtained in the prospective study. However, the strength
of this article is that the values for RA area selected for pooled
analysis have been compared with data that have been prospectively assessed. The prospective examinations used actual standards in the definition of healthy subjects and avoided referral
bias by the assessment of subjects who ask for a job certificate.
If we had referred to the prospective study only, reference values for absolute RA area would have been slightly smaller than
15 cm2 in women and 16 cm2 in men.
The majority of subjects analyzed in the prospective study
and in the pooled analysis were young (<45 years of age).
There is a lack of data describing RA area in children or
subjects >50 years of age. In older subjects, the definition of
“healthy” would need a detailed diagnostic workup, including
right-sided and left-sided heart catheterization. However, the
findings in the study of Bommer et al22 indicate that RA area
in subjects of older age do not significantly exceed the reference values confirmed in this study.
Only a few studies have been excluded from this pooled
analysis. Their values obtained for RA area would not have
changed the reference values obtained in the analysis. We chose
the 95% quantiles as normal reference values because the largest 5% of values may indicate pathological processes. Another
quantile such as 97.5% could have been considered but would
have changed the resulting reference values only slightly.
Conclusions
To the best of our knowledge, this is the largest data set to
describe RA size in adult healthy subjects (<50 years of age).
Cutoff values for RA area were significantly different in
women (15 cm2) and men (16 cm2); therefore, sex-specific values should be used in the future. Age, sex, BSA, and high-level
endurance training were determinants of RA area. Further
studies in children and subjects >50 years of age are needed.
Disclosures
None.
References
1. Bustamante-Labarta M, Perrone S, De La Fuente RL, Stutzbach P, De La
Hoz RP, Torino A, Favaloro R. Right atrial size and tricuspid regurgitation
severity predict mortality or transplantation in primary pulmonary hypertension. J Am Soc Echocardiogr. 2002;15(pt 2):1160–1164.
2. Raymond RJ, Hinderliter AL, Willis PW, Ralph D, Caldwell EJ, Williams
W, Ettinger NA, Hill NS, Summer WR, de Boisblanc B, Schwartz T, Koch
G, Clayton LM, Jöbsis MM, Crow JW, Long W. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J Am
Coll Cardiol. 2002;39:1214–1219.
3. Grapsa J, Gibbs JS, Cabrita IZ, Watson GF, Pavlopoulos H, Dawson D,
Gin-Sing W, Howard LS, Nihoyannopoulos P. The association of clinical outcome with right atrial and ventricular remodelling in patients with
pulmonary arterial hypertension: study with real-time three-dimensional
echocardiography. Eur Heart J Cardiovasc Imaging. 2012;13:666–672.
4. Guerra VC, Coles J, Smallhorn JF. Aneurysm of right atrium diagnosed
by 3-dimensional real-time echocardiogram. J Am Soc Echocardiogr.
2005;18:1221.
5. Gaynor SL, Maniar HS, Prasad SM, Steendijk P, Moon MR. Reservoir and
conduit function of right atrium: impact on right ventricular filling and cardiac output. Am J Physiol Heart Circ Physiol. 2005;288:H2140–H2145.
6. Gaynor SL, Maniar HS, Bloch JB, Steendijk P, Moon MR. Right atrial
and ventricular adaptation to chronic right ventricular pressure overload.
Circulation. 2005;112(suppl):I212–I218.
7. Kushner FG, Lam W, Morganroth J. Apex sector echocardiography in
evaluation of the right atrium in patients with mitral stenosis and atrial
septal defect. Am J Cardiol. 1978;42:733–737.
8. Cioffi G, de Simone G, Mureddu G, Tarantini L, Stefenelli C. Right atrial
size and function in patients with pulmonary hypertension associated
with disorders of respiratory system or hypoxemia. Eur J Echocardiogr.
2007;8:322–331.
9. Grünig E, Barner A, Bell M, Claussen M, Dandel M, Dumitrescu D, Gorenflo M, Holt S, Kovacs G, Ley S, Meyer JF, Pabst S, Riemekasten G, Saur
J, Schwaiblmair M, Seck C, Sinn L, Sorichter S, Winkler J, Leuchte HH.
Non-invasive diagnosis of pulmonary hypertension: ESC/ERS guidelines
with updated commentary of the Cologne Consensus Conference 2011.
Int J Cardiol. 2011;154(suppl 1):S3–12.
10. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA,
Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau
G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau
G. Guidelines for the diagnosis and treatment of pulmonary hypertension.
Eur Respir J. 2009;34:1219–1263.
11.Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB. Guidelines for the
echocardiographic assessment of the right heart in adults: a report from the
American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society
of Cardiology, and the Canadian Society of Echocardiography. J Am Soc
Echocardiogr. 2010;23:685–713; quiz 786.
12. Triulzi MMD, Gillam LD, Gentile F, Newell JB, Weyman BS, Weyman
AE. Normal adult cross-sectional echocardiographic values: linear
dimensions and chamber areas. Echocardiogr Rev Cardiovasc Ultrasound.
1984;1:403–426.
13. 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; Chamber Quantification Writing Group;
American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. 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;18:1440–1463.
14. D’Andrea A, Riegler L, Golia E, Cocchia R, Scarafile R, Salerno G, Pezzullo E, Nunziata L, Citro R, Cuomo S, Caso P, Di Salvo G, Cittadini A,
Russo MG, Calabrò R, Bossone E. Range of right heart measurements in
124 Circ Cardiovasc Imaging January 2013
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
top-level athletes: the training impact [published online ahead of print July
5, 2011]. Int J Cardiol. doi:10.1016/j.ijcard.2011.06.058.
15. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic
pressure by Doppler ultrasound in patients with tricuspid regurgitation.
Circulation. 1984;70:657–662.
16. Ommen SR, Nishimura RA, Hurrell DG, Klarich KW. Assessment of right
atrial pressure with 2-dimensional and Doppler echocardiography: a simultaneous catheterization and echocardiographic study. Mayo Clin Proc.
2000;75:24–29.
17. Du Bois D, Du Bois EF. A formula to estimate the approximate surface
area if height and weight be known; 1916. Nutrition. 1989;5:303–311.
18. Lambertz H, Heiliger R, Flachskampf FA, Wohltmann D, Krebs W, Mittermayer C. A new echocardiographic procedure for calculation of the accurate volume of the right atrium. Z Kardiol. 1986;75:342–354.
19. Lambertz H, Krebs W, Soeding S, Wohltmann D, Sechtem U, Kemmer
HP. Determination of the size of the right atrium in patients with pulmonary hypertension using 2-dimensional echocardiography. Z Kardiol.
1984;73:646–653.
20. Wang Y, Gutman JM, Heilbron D, Wahr D, Schiller NB. Atrial volume in
a normal adult population by two-dimensional echocardiography. Chest.
1984;86:595–601.
21. Mansencal N, Marcadet DM, Martin F, Montalvan B, Dubourg O. Echocardiographic characteristics of professional tennis players at the Roland
Garros French Open. Am Heart J. 2007;154:527–531.
22. Bommer W, Weinert L, Neumann A, Neef J, Mason DT, DeMaria A. Determination of right atrial and right ventricular size by two-dimensional
echocardiography. Circulation. 1979;60:91–100.
23. Cacho A, Prakash R, Sarma R, Kaushik VS. Usefulness of two-dimensional echocardiography in diagnosing right ventricular hypertrophy.
Chest. 1983;84:154–157.
24. Huez S, Faoro V, Guénard H, Martinot JB, Naeije R. Echocardiographic and tissue Doppler imaging of cardiac adaptation to high altitude
in native highlanders versus acclimatized lowlanders. Am J Cardiol.
2009;103:1605–1609.
25. Kelly NF, Walters DL, Hourigan LA, Burstow DJ, Scalia GM. The relative atrial index (RAI): a novel, simple, reliable, and robust transthoracic
echocardiographic indicator of atrial defects. J Am Soc Echocardiogr.
2010;23:275–281.
26. Reeves WC, Hallahan W, Schwiter EJ, Ciotola TJ, Buonocore E, Davidson
W. Two-dimensional echocardiographic assessment of electrocardiographic criteria for right atrial enlargement. Circulation. 1981;64:387–391.
27. Keller AM, Gopal AS, King DL. Left and right atrial volume by freehand
three-dimensional echocardiography: in vivo validation using magnetic
resonance imaging. Eur J Echocardiogr. 2000;1:55–65.
28. Ogunyankin KO, Liu K, Lloyd-Jones DM, Colangelo LA, Gardin JM.
Reference values of right ventricular end-diastolic area defined by ethnicity and gender in a young adult population: the CARDIA study. Echocardiography. 2011;28:142–149.
29. Baggish AL, Wood MJ. Athlete’s heart and cardiovascular care of the athlete: scientific and clinical update. Circulation. 2011;123:2723–2735.
30. La Gerche A, Burns AT, Mooney DJ, Inder WJ, Taylor AJ, Bogaert J,
Macisaac AI, Heidbüchel H, Prior DL. Exercise-induced right ventricular
dysfunction and structural remodelling in endurance athletes. Eur Heart J.
2012;33:998–1006.
31. Trivax JE, Franklin BA, Goldstein JA, Chinnaiyan KM, Gallagher MJ,
deJong AT, Colar JM, Haines DE, McCullough PA. Acute cardiac effects
of marathon running. J Appl Physiol. 2010;108:1148–1153.
32. Ector J, Ganame J, van der Merwe N, Adriaenssens B, Pison L, Willems R,
Gewillig M, Heidbüchel H. Reduced right ventricular ejection fraction in
endurance athletes presenting with ventricular arrhythmias: a quantitative
angiographic assessment. Eur Heart J. 2007;28:345–353.
33. Roy A, Doyon M, Dumesnil JG, Jobin J, Landry F. Endurance vs. strength
training: comparison of cardiac structures using normal predicted values.
J Appl Physiol. 1988;64:2552–2557.
Clinical Perspective
Right atrial size is important in several indications such as screening, diagnosis, and follow-up assessment of patients with
pulmonary hypertension. This is the first study to provide normal reference values for right atrial area in a large number of
healthy subjects. Sex differences and the influence of age, body surface area, and training status on echocardiographic right
atrial area are confirmed for the first time. Because an enlarged atrium may be an early indicator for pulmonary hypertension
or primary diseases of the right heart, the results are of high clinical impact. For clinical practice, it is more convenient to
measure the absolute area instead of performing corrections for body surface area. Therefore, the finding that women and
men have significantly different absolute right atrial areas is of clinical importance. Cutoff values for right atrial area were
significantly different in women (15 cm2) and men (16 cm2); therefore, sex-specific values should be used in the future.
Reference Values for and Determinants of Right Atrial Area in Healthy Adults by
2-Dimensional Echocardiography
Ekkehard Grünig, Philipp Henn, Antonello D'Andrea, Martin Claussen, Nicola Ehlken, Felicitas
Maier, Robert Naeije, Christian Nagel, Felix Prange, Johannes Weidenhammer, Christine
Fischer and Eduardo Bossone
Downloaded from http://circimaging.ahajournals.org/ by guest on May 14, 2017
Circ Cardiovasc Imaging. 2013;6:117-124; originally published online November 29, 2012;
doi: 10.1161/CIRCIMAGING.112.978031
Circulation: Cardiovascular Imaging is published by the American Heart Association, 7272 Greenville Avenue,
Dallas, TX 75231
Copyright © 2012 American Heart Association, Inc. All rights reserved.
Print ISSN: 1941-9651. Online ISSN: 1942-0080
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circimaging.ahajournals.org/content/6/1/117
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Circulation: Cardiovascular Imaging can be obtained via RightsLink, a service of the Copyright Clearance
Center, not the Editorial Office. Once the online version of the published article for which permission is being
requested is located, click Request Permissions in the middle column of the Web page under Services. Further
information about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation: Cardiovascular Imaging is online at:
http://circimaging.ahajournals.org//subscriptions/