Background
Despite the common practice of indexing left ventricular dimensions to body surface area, there remains a lack of indexed normal right ventricular (RV) two-dimensional caliper measurements. Variations in ranges for normal RV dimensions have been shown to exist, and indexing RV dimensions according to body surface area may help reduce this and provide a standardization useful for clinical practice. The aim of this study was to prospectively establish both absolute and indexed normal dimensions for the right ventricle using standardized positions in a multiethnic population. Furthermore, the effects of both gender and ethnicity on both the absolute and indexed results were also evaluated.
Methods
Two hundred five healthy volunteers from four ethnic backgrounds (Indian, Chinese, Malay, and European) were prospectively enrolled and underwent two-dimensional echocardiography according to a set protocol. Ten measurements were made in conjunction with previous research. Intraobserver and interobserver and test-retest variability was assessed using coefficients of variation and intraclass correlation coefficients.
Results
Male absolute results exceeded female absolute results in 90% of measurements ( P = .003). European absolute results (male and female) were significantly larger in up to eight of 10 measurements ( P = .01). When indexed, female results became significantly larger ( P < .001) than male results. Indexing was able to reduce the number of statistical differences between male ethnic groups. Measurements showed good levels of intraobserver and interobserver variability for apical and short-axis measurements.
Conclusions
Gender and body surface area play an important part in the determination of normal RV reference ranges, whereas ethnicity has little influence. Results using the suggested RV markers for these measurements showed good repeatability.
Clinical evaluation of the right ventricle is important in many cardiac diseases, requiring an in-depth understanding of physiology and anatomy. The complex geometry of the right ventricle often limits its echocardiographic assessment, and historically, the left ventricle has been studied in much greater detail. Indexing left ventricular (LV) dimensions to body surface area (BSA) is accepted practice, although data giving indices of normal morphology in the right ventricle are insufficient by comparison.
There is a need to update normal indices for the right ventricle to provide clinicians with the most accurate information on which to base patient treatment decisions.
Although cardiac magnetic resonance is regarded as the “gold standard,” echocardiography remains the most commonly used method of right ventricular (RV) assessment because it is noninvasive, widely available, relatively inexpensive, and free of side effects.
Echocardiographic Assessment
For both qualitative and quantitative evaluation of the right ventricle, multiple projections are required to clearly assess each of the chamber components. American Society of Echocardiography (ASE) and European Association of Echocardiography (EAE) guidelines discuss the assessment of the right ventricle using both previously described methods and expert consensus, but unlike the left ventricle, there was no inclusion of results indexing RV values to BSA.
More recent ASE and EAE guidelines, however, highlight the lack of indexed values for the right ventricle. They also acknowledge the need to diversify reference ranges among different populations and to derive gender-specific reference ranges, which have been shown to influence a number of echocardiographic parameters. They suggest that the data presented in the 2006 guidelines were too limited, indicating that mea-surements made at the upper reference values could be misclassified.
Alongside more established variables such as gender, age, and BSA, ethnicity has also been shown to be a factor in determining normal echocardiographic measurements.
Therefore, we acquired two-dimensional echocardiographic data prospectively on a multiethnic group of healthy individuals to establish both absolute (centimeters) and indexed (centimeters per square meter) measurements of the normal right ventricle while defining the location of these measurements using previous research as a comparison and to assess the potential impact that gender and ethnicity may have. Furthermore, we also used RV diameter at the tricuspid annular level (RVD-AN) as a further measurement to describe the right ventricle.
Methods
Study Population
Two hundred five healthy volunteers from four ethnic backgrounds (Chinese, European, Indian, and Malay) were prospectively enrolled and underwent standardized echocardiographic assessment. Full exclusion criteria are shown in Table 1 . Ages ranged from 19 to 71 years (mean, 42 years; 53% men). Screening of volunteers involved 12-lead electrocardiography, a health questionnaire, and a physical examination.
| Systemic hypertension |
| Diabetes |
| History of thromboembolic disease |
| Asthma/chronic obstructive pulmonary disease |
| Obstructive sleep apnea |
| Collagen vascular disease |
| LV systolic dysfunction |
| Aortic/mitral valve disease |
| Congenital heart disease |
| Human immunodeficiency virus infection |
| Portal hypertension/pulmonary arterial hypertension |
| History of anorexigen use |
Initial participant ethnicity was chosen on the basis of the largest national demographic populations from both Malaysia and the United Kingdom, as suggested by the respective national census data. Volunteer ethnicity was self-declared during consenting. The European sample was recruited through the Royal United Hospital (Bath, United Kingdom), with the Malay, Chinese, and Indian samples recruited via the Gleneagles Medical Centre (Penang, Malaysia). All scans were performed by a team of four accredited sonographers from the Royal United Hospital.
Height (centimeters) and weight (kilograms) were documented for the calculation of BSA using the Mosteller formula. All volunteers gave informed consent before taking part in the study. The study was granted ethical approval from the local research and ethics committee.
Image Acquisition
Echocardiography was performed in the left lateral position. All scans were conducted using a standardized protocol devised for this study in conjunction with both ASE guidelines and previous work on two GE Vivid 7 devices (GE Vingmed Ultrasound AS, Horten, Norway). All images were digitally stored for offline analysis using specific analytical software (EchoPAC version 8.0; GE Vingmed Ultrasound AS).
Measurements
Measurements were made using those suggested by Foale et al. and ASE and EAE guidelines for both reference and comparison. Table 2 lists the location of each measurement. Volunteers underwent a full quantitative assessment of LV size and function to ensure that no LV systolic dysfunction, significant diastolic dysfunction, or valvular abnormalities existed.
| Measurement | Location of measurement |
|---|---|
| RVD-AN | The hinge point attachment of septal leaflet to septal wall and anterior leaflet to lateral wall [5,17] |
| RVD-1 | Taken within one third of the distance below the tricuspid valve annulus toward the RV apex [5] |
| RVD-2 | Mid-RV diameter measured at the level of the LV papillary muscles [7] |
| RVD-3 | Midpoint of RVD-AN in the major axis to the endocardial boarder of the RV apex [5] |
| RVOT-1 | Perpendicular to the central point of aortic valve closure line to the endocardial border; measurement made at peak of the R wave [5] |
| RVOT-2 | Measurement made just below the pulmonary valve annulus, inner border to inner border [5] |
| RVOT-3 | Proximal region of the RVOT in PLAX view; interventricular septum to anterior RV free wall [5] |
| RV WT | M-mode echocardiography of the RV free wall in the PLAX view [5] |
| RVESA | Endocardial border traced from apical four-chamber view at the time of the smallest RV cavity |
| RVEDA | Endocardial border traced from the apical four-chamber view at end-diastole |
Ten measurements were made for the assessment of RV size (centimeters; see Figure 1 ). These were conducted in the parasternal long-axis view to assess RV outflow tract (RVOT) width (RVOT diameter 3) and RV wall thickness (WT), the parasternal short-axis view (at the aortic valve level) to assess the RVOT (perpendicular to the aortic valve [RVOT-1] and measured at the pulmonary valve annulus [RVOT-2]), and the apical four-chamber view to measure the RV inflow and apex. Images were angled to maintain a consistent view of the RV lateral wall and septum, with optimization of the apex to give clear delineation.
Measurements were made at end-diastole, identified using the widest tricuspid valve leaflet excursion before the onset of the QRS complex. All cavity measurements were made from inside edge to inside edge.
Measurement of the RV minor axis diameter (RVD-1) was made within the basal third of the right ventricle below the tricuspid valve, standardized in location to one third of the RVD-3 length (RV major axis diameter). RVD-2 was measured in the RV minor axis at papillary muscle level. In addition, an annular measurement, RVD-AN (see Table 2 ), was also taken and used as a reference point for the calculation of RVD-3.
RV function was assessed using tricuspid annular systolic plane excursion (normal values ≥ 1.6 cm), RV fractional area change (normal values > 35%), and pulsed Doppler peak velocity at the annulus (normal values > 10 m/sec). Images were optimized using both sector width and focus position. Images were all taken at end-expiration to minimize translational movement and lung artifacts.
Images were initially considered of adequate quality if each of the associated valves could be visualized throughout the parasternal and apical views, and the major parts of the cavities could be seen. Each image was optimized to ensure that the relevant anatomy was available for measurement and at the best available orientation while maintaining the appropriate plane in which to measure the widest dimension.
Statistical Analysis
All measurements were assessed for normality using the Kolmogorov-Smirnov test. Data that conformed to a normal distribution are presented as mean ± SD or were log transformed for analysis if appropriate. Reference intervals were calculated as mean ± 1.96 SD, giving 95% upper and lower reference limits. Indexed data were derived by dividing the absolute value by the respective BSA to give each measurement in centimeters per square meter. Comparisons amongst ethnic groups were assessed using analysis of variance, with Tukey’s test used to identify where the differences lay. Differences between genders were compared using t tests. Forward stepwise multivariate analysis was used to determine the dependence of the measured parameters on ethnicity, gender, and BSA. The influence of age on each of the measured parameters was also investigated on the basis of the cohort data.
Data Reproducibility
Reproducibility for each measurement was assessed in a subset of 40 volunteers chosen at random. An accredited reader (reader 1, D.A.) experienced in echocardiographic analysis undertook all initial measurements in the cohort and then remeasured the same images >2 weeks after the first analysis, blinded to the initial results. This was used to establish the intraobserver variability for each measurement. The same subset was then evaluated by a second accredited reader (reader 2, J. Sparey), blinded to the results of previous analysis, to assess the interobserver variability.
The subset of 40 volunteers also contained 10 volunteers who underwent a second scan performed by the original sonographer. Analysis of these additional images was performed by reader 1, and the results were then used to calculate test-retest variability.
Interobserver, intraobserver, and test-retest variability was expressed using intraclass correlation coefficients (ICCs) and coefficients of variation (COVs). The COV was calculated using the standard deviation of the difference between the two measurements, multiplied by 100 and divided by the mean value, calculated as a percentage. A COV ≤ 10% was considered excellent. Using a method for the assessment of ICCs previously reported, the following guidelines suggested by Shrout and Fleiss were implemented: ICC > 0.75 = excellent, ICC 0.4 to 0.75 = good, and ICC < 0.40 = poor. All analysis was conducted using SPSS version 19.0 (SPSS, Inc., Chicago, IL).
Methods
Study Population
Two hundred five healthy volunteers from four ethnic backgrounds (Chinese, European, Indian, and Malay) were prospectively enrolled and underwent standardized echocardiographic assessment. Full exclusion criteria are shown in Table 1 . Ages ranged from 19 to 71 years (mean, 42 years; 53% men). Screening of volunteers involved 12-lead electrocardiography, a health questionnaire, and a physical examination.
| Systemic hypertension |
| Diabetes |
| History of thromboembolic disease |
| Asthma/chronic obstructive pulmonary disease |
| Obstructive sleep apnea |
| Collagen vascular disease |
| LV systolic dysfunction |
| Aortic/mitral valve disease |
| Congenital heart disease |
| Human immunodeficiency virus infection |
| Portal hypertension/pulmonary arterial hypertension |
| History of anorexigen use |
Initial participant ethnicity was chosen on the basis of the largest national demographic populations from both Malaysia and the United Kingdom, as suggested by the respective national census data. Volunteer ethnicity was self-declared during consenting. The European sample was recruited through the Royal United Hospital (Bath, United Kingdom), with the Malay, Chinese, and Indian samples recruited via the Gleneagles Medical Centre (Penang, Malaysia). All scans were performed by a team of four accredited sonographers from the Royal United Hospital.
Height (centimeters) and weight (kilograms) were documented for the calculation of BSA using the Mosteller formula. All volunteers gave informed consent before taking part in the study. The study was granted ethical approval from the local research and ethics committee.
Image Acquisition
Echocardiography was performed in the left lateral position. All scans were conducted using a standardized protocol devised for this study in conjunction with both ASE guidelines and previous work on two GE Vivid 7 devices (GE Vingmed Ultrasound AS, Horten, Norway). All images were digitally stored for offline analysis using specific analytical software (EchoPAC version 8.0; GE Vingmed Ultrasound AS).
Measurements
Measurements were made using those suggested by Foale et al. and ASE and EAE guidelines for both reference and comparison. Table 2 lists the location of each measurement. Volunteers underwent a full quantitative assessment of LV size and function to ensure that no LV systolic dysfunction, significant diastolic dysfunction, or valvular abnormalities existed.
| Measurement | Location of measurement |
|---|---|
| RVD-AN | The hinge point attachment of septal leaflet to septal wall and anterior leaflet to lateral wall [5,17] |
| RVD-1 | Taken within one third of the distance below the tricuspid valve annulus toward the RV apex [5] |
| RVD-2 | Mid-RV diameter measured at the level of the LV papillary muscles [7] |
| RVD-3 | Midpoint of RVD-AN in the major axis to the endocardial boarder of the RV apex [5] |
| RVOT-1 | Perpendicular to the central point of aortic valve closure line to the endocardial border; measurement made at peak of the R wave [5] |
| RVOT-2 | Measurement made just below the pulmonary valve annulus, inner border to inner border [5] |
| RVOT-3 | Proximal region of the RVOT in PLAX view; interventricular septum to anterior RV free wall [5] |
| RV WT | M-mode echocardiography of the RV free wall in the PLAX view [5] |
| RVESA | Endocardial border traced from apical four-chamber view at the time of the smallest RV cavity |
| RVEDA | Endocardial border traced from the apical four-chamber view at end-diastole |
Ten measurements were made for the assessment of RV size (centimeters; see Figure 1 ). These were conducted in the parasternal long-axis view to assess RV outflow tract (RVOT) width (RVOT diameter 3) and RV wall thickness (WT), the parasternal short-axis view (at the aortic valve level) to assess the RVOT (perpendicular to the aortic valve [RVOT-1] and measured at the pulmonary valve annulus [RVOT-2]), and the apical four-chamber view to measure the RV inflow and apex. Images were angled to maintain a consistent view of the RV lateral wall and septum, with optimization of the apex to give clear delineation.
Measurements were made at end-diastole, identified using the widest tricuspid valve leaflet excursion before the onset of the QRS complex. All cavity measurements were made from inside edge to inside edge.
Measurement of the RV minor axis diameter (RVD-1) was made within the basal third of the right ventricle below the tricuspid valve, standardized in location to one third of the RVD-3 length (RV major axis diameter). RVD-2 was measured in the RV minor axis at papillary muscle level. In addition, an annular measurement, RVD-AN (see Table 2 ), was also taken and used as a reference point for the calculation of RVD-3.
RV function was assessed using tricuspid annular systolic plane excursion (normal values ≥ 1.6 cm), RV fractional area change (normal values > 35%), and pulsed Doppler peak velocity at the annulus (normal values > 10 m/sec). Images were optimized using both sector width and focus position. Images were all taken at end-expiration to minimize translational movement and lung artifacts.
Images were initially considered of adequate quality if each of the associated valves could be visualized throughout the parasternal and apical views, and the major parts of the cavities could be seen. Each image was optimized to ensure that the relevant anatomy was available for measurement and at the best available orientation while maintaining the appropriate plane in which to measure the widest dimension.
Statistical Analysis
All measurements were assessed for normality using the Kolmogorov-Smirnov test. Data that conformed to a normal distribution are presented as mean ± SD or were log transformed for analysis if appropriate. Reference intervals were calculated as mean ± 1.96 SD, giving 95% upper and lower reference limits. Indexed data were derived by dividing the absolute value by the respective BSA to give each measurement in centimeters per square meter. Comparisons amongst ethnic groups were assessed using analysis of variance, with Tukey’s test used to identify where the differences lay. Differences between genders were compared using t tests. Forward stepwise multivariate analysis was used to determine the dependence of the measured parameters on ethnicity, gender, and BSA. The influence of age on each of the measured parameters was also investigated on the basis of the cohort data.
Data Reproducibility
Reproducibility for each measurement was assessed in a subset of 40 volunteers chosen at random. An accredited reader (reader 1, D.A.) experienced in echocardiographic analysis undertook all initial measurements in the cohort and then remeasured the same images >2 weeks after the first analysis, blinded to the initial results. This was used to establish the intraobserver variability for each measurement. The same subset was then evaluated by a second accredited reader (reader 2, J. Sparey), blinded to the results of previous analysis, to assess the interobserver variability.
The subset of 40 volunteers also contained 10 volunteers who underwent a second scan performed by the original sonographer. Analysis of these additional images was performed by reader 1, and the results were then used to calculate test-retest variability.
Interobserver, intraobserver, and test-retest variability was expressed using intraclass correlation coefficients (ICCs) and coefficients of variation (COVs). The COV was calculated using the standard deviation of the difference between the two measurements, multiplied by 100 and divided by the mean value, calculated as a percentage. A COV ≤ 10% was considered excellent. Using a method for the assessment of ICCs previously reported, the following guidelines suggested by Shrout and Fleiss were implemented: ICC > 0.75 = excellent, ICC 0.4 to 0.75 = good, and ICC < 0.40 = poor. All analysis was conducted using SPSS version 19.0 (SPSS, Inc., Chicago, IL).
Results
Of the 205 volunteers, three (1.4%) were excluded from the study because of cardiac anomalies. Image acquisition ranged from 71.2% to 92%.
Table 3 summarizes the volunteer demographics. All subsequent analysis of both normalized and absolute measurements was conducted on gender-specific data. The results, organized by ethnic group, are shown in Tables 4 and 5 for absolute measurements and Tables 6 and 7 for results normalized to BSA.
| Variable | Value |
|---|---|
| Age (y) | 42 ± 12 |
| Men | 53% |
| Ethnicity | |
| Chinese | 66 |
| European | 45 |
| Indian | 46 |
| Malay | 48 |
| Height (cm) | 165.00 ± 10 |
| Weight (kg) | 68.68 ± 14 |
| BSA (m 2 ) | 1.77 ± 0.21 |
| Body mass index (kg/m 2 ) | 25.3 ± 6 |
| Measurement | Chinese | European | Indian | Malay | ||||
|---|---|---|---|---|---|---|---|---|
| n | Mean ± SD | n | Mean ± SD | n | Mean ± SD | n | Mean ± SD | |
| RVD-AN | 26 | 2.33 ∗ ± 0.39 | 21 | 2.74 ± 0.35 | 22 | 2.30 ∗ ± 0.32 | 22 | 2.27 ∗ ± 0.39 |
| RVD-1 | 26 | 3.07 ± 0.27 | 19 | 3.2 ± 0.41 | 18 | 3.18 ± 0.34 | 17 | 3.05 ± 0.27 |
| RVD-2 | 27 | 3.02 ± 0.42 | 20 | 3.33 ± 0.39 | 20 | 3.07 ± 0.50 | 22 | 2.87 † ± 0.39 |
| RVD-3 | 26 | 7.34 ∗ ± 0.47 | 21 | 8.29 ± 0.6 | 21 | 7.30 ∗ ± 0.41 | 21 | 7.09 ∗ ± 0.47 |
| RVOT-1 | 29 | 2.91 ∗ ± 0.39 | 21 | 3.39 ± 0.41 | 23 | 2.71 ∗ ± 0.35 | 28 | 2.77 ∗ ± 0.29 |
| RVOT-2 § | 29 | 2.12 | 20 | 2.04 | 22 | 1.95 | 26 | 2.01 |
| RVOT-3 | 29 | 2.47 ∗ ± 0.34 | 22 | 2.96 ± 0.36 | 24 | 2.5 ∗ ± 0.28 | 26 | 2.47 ∗ ± 0.27 |
| RV WT | 30 | 0.42 ± 0.06 | 22 | 0.43 ± 0.06 | 24 | 0.37 ‡ ± 0.06 | 26 | 0.4 ± 0.08 |
| RVESA | 26 | 8.49 ∗ ± 2.11 | 18 | 10.87 ± 2.37 | 15 | 7.52 ∗ ± 1.79 | 19 | 7.67 ∗ ± 1.52 |
| RVEDA | 26 | 16.15 ∗ ± 2.6 | 18 | 20.75 ± 4.53 | 15 | 14.30 ∗ ± 2.84 | 19 | 14.26 ∗ ± 2.36 |
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