Background
Compromise of right heart function is an important feature of many forms of congenital heart disease, and right atrial (RA) pressure is clinically relevant. Inferior vena cava (IVC) diameter and inspiratory collapse are indices of RA pressure, but pediatric data are lacking.
Methods
RA measurements, systemic venous diameters, and Doppler filling fractions were prospectively investigated in healthy volunteer children and adolescents. The IVC was measured in its long axis just above the junction with the hepatic veins in the subxiphoid view and the superior vena cava at its junction with the right atrium in the right parasternal view. The changes in IVC diameter (IVCD) during quiet respiration and with a sniff were recorded. Hepatic venous systolic filling fraction was calculated from Doppler velocities in the first hepatic vein. RA major-axis length, area, and volume were measured from the apical four-chamber view. Three measurements of each parameter were averaged over at least three respiratory cycles. The IVC collapsibility index (IVCCI) was calculated as [(IVCDmax − IVCDmin)/IVCDmax] × 100. Substituting IVCDsniff for IVCDmin in the formula, the IVCCIsniff was calculated.
Results
Of 132 subjects enrolled, data in 120 (mean age, 8.3 ± 4.5 years) were analyzed. The maximal (expiratory) and minimal (inspiratory) diameters during free breathing were 12.1 ± 3.8 and 8.9 ± 3.8 mm for the IVC and 11.9 ± 3.4 and 7.9 ± 2.6 mm for the superior vena cava. IVCCImin and IVCCIsniff were 30 ± 13 and 47 ± 18, respectively. The RA major-axis length, area, and indexed maximal volume were 3.7 ± 0.7 cm, 10.3 ± 3.6 cm 2 , and 22.3 ± 7.0 mL/m 2 , respectively. Correlations of maximal superior vena cava and IVC dimensions with body surface area were slightly better than with age and much stronger than with RA volume. No significant correlation was found between IVCCIs and age, gender, or indexed RA volume.
Conclusions
Measurement of systemic venous diameters, collapsibility indices, and RA volumes is feasible in healthy children and adolescents. Venous diameters increase predictably with growth and so must be interpreted in light of body surface area. IVCCIs and hepatic venous filling fraction compare closely with those reported in adults. Pediatric nomograms for these parameters are provided, and they should next be evaluated for relation to directly measured RA pressure in this age group.
Echocardiographic assessment of right heart function is of great importance in clinical cardiology. Right ventricular (RV) diastolic dysfunction causes impaired RV filling and elevation of diastolic pressures in the right ventricle and right atrium. The increased right atrial (RA) pressure is transmitted to the inferior vena cava (IVC), resulting in its dilatation. IVC diameter and inspiratory collapse are used in combination for estimation of RA pressure in adult patients. The percentage decrease in IVC diameter during inspiration (collapsibility index) has been shown to correlate with RA pressure. IVC diameter has also been shown to have prognostic significance in chronic heart failure: increasing diameter identifies patients with adverse outcomes. For the superior vena cava (SVC), normal Doppler flow patterns and respirophasic variations has been described in adults. In neonates, SVC flow is considered a surrogate measure of systemic blood flow and has been characterized in preterm and term neonates in the first 3 days of life.
Hepatic venous Doppler is also used for the prediction of RA pressure. Normally with inspiration, there is a significant increase in the systolic and diastolic forward flow in the hepatic veins, and the systolic forward flow decreases as RA pressure increases. A hepatic venous systolic filling fraction < 55% and hepatic vein atrial reversal wave velocity greater than the systolic forward velocity are indicative of elevated RA pressure in adults. In addition to these indices, the American Society of Echocardiography recommends RA dimensions (major-axis length and area) for the assessment of RA pressure. RA volume is a marker of RV pressure load and diastolic dysfunction that correlates with RA pressure, but there are limited data on standardized RA volumes derived by echocardiography in children and adults.
Right heart dysfunction is commonly encountered in congenital and acquired heart disease in children and is closely related to patient outcomes. Reduced RV compliance and/or increased filling pressures in patients with congenital heart disease expose the right atrium to pressure load and dilatation. Evaluation of systemic veins and right atrium could be useful as indicators of right heart function in the pediatric age group, yet there is little reason to assume normal values in adults can be applied in children. Moreover, there are very few data on the use of the systemic veins and the right atrium as part of functional assessment of the right heart in children. Insights into RV diastolic function gained from these indices could be valuable, given the limitations of standard two-dimensional echocardiography in the functional assessment of the right ventricle. The purposes of this investigation were (1) to test the hypothesis that echocardiographic indices of right heart function vary with body surface area (BSA) in children and (2) to determine normal values for systemic venous diameters, Doppler filling fractions, IVC collapsibility indices (IVCCIs), and RA measurements in a sample of healthy children representing the broad range of age and size seen in pediatrics.
Methods
Patients
This was a single-center prospective investigation. Two-dimensional echocardiographic studies were performed exclusively for research purposes, and healthy volunteer children were enrolled between January 2012 and March 2013. These children were recruited in response to an advertisement inviting participation, which was approved by the institutional review board and was placed in the institutional employee newsletter. Inclusion criteria were (1) age 1 to 18 years; (2) no history of any heart disease, hypertension, or any other systemic disease; and (3) the provision of informed consent. The institutional review board for human subjects research approved the study protocol, and the parents of all recruited subjects signed informed consent. Demographic data were collected, including gender, date of birth, height, weight, heart rate, and systemic blood pressure. BSA was calculated using the Haycock formula.
Image Acquisition
All recruited subjects underwent complete two-dimensional echocardiography with spectral and color flow Doppler examinations in a nonsedated state using a commercially available ultrasound system (Vivid E9; GE Healthcare, Milwaukee, WI). All subjects had structurally and functionally normal hearts and were in sinus rhythm. None of the subjects had more than trivial tricuspid valve regurgitation. All acquisitions were in the supine position and had a minimum of three beats with simultaneously recorded electrocardiograms and respiratory tracings to time the events during subsequent analysis. The transducer frequency, two-dimensional sector width and depth, and imaging processor settings were selected according to subjects’ body sizes, with the aim of achieving the highest imaging frame rate while retaining image quality adequate for accurate measurement. A single research sonographer (L.L.) acquired all the images and performed the measurements below. All data were stored digitally for analysis using EchoPAC BT11 software (GE Healthcare).
Systemic Venous Diameters and Doppler
Systemic venous diameters were measured offline as shown in Figure 1 . The IVC diameter was measured in the long axis of the IVC at end-expiration and just proximal to the entry of the hepatic veins as recommended by the American Society of Echocardiography guidelines and standards documents. To assess IVCCI, the changes in IVC diameter with quiet respiration and with a sniff were recorded. IVCCI was calculated as 100 × (maximal diameter − minimal diameter)/maximal diameter, and IVCCIsniff was calculated as 100 × (maximal diameter − minimal diameter with sniff)/maximal diameter. To make these measurements, we chose an approach consistent with that of other investigators, using the two-dimensional technique for its spatial orientation advantages over M-mode imaging, despite the latter’s superior temporal resolution. The maximal diameter of the proximal SVC was measured at its entry into the right atrium from the right parasternal view. The Doppler velocities of systolic and diastolic waves in the first hepatic vein were measured from the subxiphoid image using color Doppler as a guide and placing the sample volume 0.5 to 1 cm within the vein near its entry into the IVC ( Figure 2 ). The hepatic venous systolic filling fraction was calculated as systolic velocity/(systolic velocity + diastolic velocity). Similarly, pulsed Doppler measurements in the IVC were recorded from the right parasternal view and in the SVC from the suprasternal view ( Figure 2 ) for the calculation of SVC and IVC filling fractions. The average of three measurements was taken for each parameter.
Measurement of RA Area and Volumes
The RA major-axis length was measured from the apical four-chamber view as the maximal distance from the center of the tricuspid annulus to the center of the superior RA wall, parallel to the interatrial septum. For measurement of RA area, the endocardium was traced at the end of ventricular systole from the lateral aspect of the tricuspid annulus to the septal aspect, excluding the SVC, IVC, and RA appendage ( Figure 1 ). For the calculation of RA volume, the single-plane area-length method was used, applying the formula 8/3π[area 2 /(major axis length)]. For each cardiac cycle, an average of three separate measurements of the maximum atrial volume was measured and indexed to BSA.
Statistical Analysis
Continuous variables are expressed as mean ± SD and discrete variables as percentages. Univariate linear regressions of each systemic venous parameter with age and BSA were performed. Correlations were explored for each measurement with BSA and age with Bonferroni correction applied for multiple comparisons. To assess intraobserver and interobserver agreement, systemic venous dimensions and RA volume measurements were repeated in 20 randomly chosen subjects by the primary observer (4 weeks after the first measurement) and a second blinded observer (Q.P.). Bland-Altman plots were derived to identify possible bias (mean divergence) and the limits of agreement (2 standard deviations of the divergence). Intraclass correlation coefficients were calculated for testing measurement variability. Mean percentage error was calculated as the absolute difference between two sets of observations divided by the mean of the observations: [|(X 1 − X 2 )|/mean(X 1 , X 2 )] × 100. Statistical analysis was performed using commercially available software (Minitab version 16.1; Minitab Inc, State College, PA).
Results
Subject Characteristics
Of 132 subjects enrolled, 12 with incomplete data were excluded, yielding a study cohort of 120. There were 52 male and 68 female patients. Table 1 shows demographics and systemic venous and RA parameters in the entire cohort. Ranges for most parameters were broad, and the value of interpretation without considering the size of the subject appeared limited.
Parameter | Mean ± SD | Range |
---|---|---|
Age (y) | 8.3 ± 4.5 | 1.0–18.0 |
BSA (m 2 ) | 1.2 ± 0.5 | 0.45–2.6 |
Proximal IVC maximal diameter (mm) | 12.1 ± 3.8 | 4.4–24.4 |
Proximal IVC minimal diameter (mm) | 8.9 ± 3.8 | 1.9–19.2 |
Proximal IVC minimal diameter with sniff (mm) | 6.6 ± 3.3 | 1.0–18.0 |
IVCCI | 30 ± 13.2 | 17.0–64.2 |
Proximal SVC maximal diameter (mm) | 11.9 ± 3.4 | 4.1–23.2 |
Proximal SVC minimal diameter (mm) | 7.9 ± 2.6 | 2.9–15.7 |
RA major-axis dimension (mm) | 37.0 ± 7.0 | 23.3–54.6 |
RA area (cm 2 ) | 10.3 ± 3.6 | 4.5–22.4 |
Indexed RA volume (mL/m 2 ) | 22.3 ± 7.0 | 9.6–45.3 |
First hepatic vein filling fraction (%) | 60.0 ± 6.8 | 39.5–75.2 |
IVC filling fraction (%) | 55 ± 6.7 | 38.2–71.0 |
SVC filling fraction (%) | 59 ± 5.0 | 44.9–73.2 |
Nomograms and Correlations
Regression models were derived for each measured parameter. The relation with BSA was linear for most measurements, but there were no significant correlations between hepatic venous filling fraction and IVCCIsniff and BSA. Correlations of maximal SVC and IVC diameters with BSA were slightly better than with age and much stronger than with RA volume. The distributions of maximal and minimal systemic venous measurements in the study cohort with BSA are shown in Figure 3 ( P < .0001). Figures 4 and 5 illustrate the mean and 2 standard deviations above and below the mean for systemic venous diameters, IVCCI, and RA measurements indexed to BSA. The hepatic venous filling fraction was 60 ± 7% and the IVCCIsniff was 47 ± 18. No significant correlation was found between IVCCIs with age or gender. RA major-axis length, area, and maximal volume all correlated well with BSA ( P < .001; Figure 5 ).