Background
Right ventricular (RV) mechanical dyssynchrony may be associated with RV dysfunction. The aim of this study was to investigate the feasibility of measuring RV synchrony in normal children using Doppler tissue imaging and two-dimensional speckle tracking.
Methods
The RV delay (difference in time to peak velocity or two-dimensional strain between the RV lateral wall and the interventricular septum) and standard deviation of time to peak velocity or strain were measured and corrected for heart rate. Intraobserver and interobserver reliabilities were analyzed.
Results
One hundred three children were studied. RV delay analysis was feasible in 95% by Doppler tissue imaging and in 63% by two-dimensional speckle tracking (99% and 84% when imaging was adequate). The mean ± 2 standard deviations RV delay by either method was <70 msec or <8% of the cardiac cycle in systole and <65 msec or <7% of the cardiac cycle in diastole. Intraobserver and interobserver variability showed small absolute differences but high variability because delays were either positive or negative.
Conclusion
This study establishes the feasibility of the measurement of RV mechanical synchrony in normal children aged 3 to 18 years.
Right ventricular (RV) dyssynchrony is important in a number of congenital and acquired cardiac conditions in children such as hypoplastic left heart syndrome, tetralogy of Fallot, pulmonary hypertension, and arrhythmogenic RV dysplasia or cardiomyopathy. RV dyssynchrony is associated with RV remodeling, RV dilatation, RV dysfunction, and decreased functional capacity. However, the feasibility and application of pediatric RV synchrony measurement have not been established. Investigation of RV dyssynchrony is important as a contributor to ventricular dysfunction and patient symptoms and prognosis and as a possible predictor of response to cardiac resynchronization therapy. Although a number of methods for quantifying RV dyssynchrony have been used, the most common has been RV intraventricular delay, defined as the difference in time to peak motion or deformation between the RV lateral wall and interventricular septum (IVS). Accordingly, the aim of this study was to establish the feasibility of RV systolic and diastolic delay, in children and adolescents, using Doppler tissue imaging (DTI) velocities and two-dimensional (2D) speckle-tracking strain. Because the standard deviation (SD) of time to peak velocity or strain among various segments has been commonly used for the left ventricle, we also tested this methodology for the right ventricle.
Methods
Study Population
A convenience sample of healthy children having undergone echocardiography within other research protocols was studied. The data in the current report have not been previously published. All subjects underwent histories, physical examinations, and full anatomic and functional echocardiography and were included in this study if the results of all these studies were normal, including qualitatively normal RV function and no more than trace tricuspid or pulmonary regurgitation. Written informed consent was obtained from the subjects or their guardians. The protocols were approved by the institutional research ethics board.
Echocardiography
Image Acquisition
Echocardiography was performed using a predetermined standardized echocardiographic protocol on a GE Vivid 7 or E-9 ultrasound system (GE Vingmed Ultrasound AS, Horten, Norway) with probe frequencies appropriate for patient size. Images were obtained during quiet respiration. Images were optimized for pulsed repetition frequency, depth, gain, compression, and frame rate. In each subject, an apical four-chamber view was obtained by 2D echocardiography (B mode) and immediately thereafter by color DTI. Raw digital data were transferred to a dedicated workstation for offline analysis (EchoPAC; GE Vingmed Ultrasound AS). Each subject was scanned by one of two sonographers (W.H., C.S.) using a single ultrasound system. Offline analysis was performed by one investigator (W.H.).
DTI
Systolic and diastolic velocity traces were derived offline from color Doppler tissue images at the basal, mid, and apical segments of the RV lateral wall and IVS using 3-mm to 6-mm sample volumes depending on subject size. The time interval between the onset of the QRS complex and peak systolic (S′) and early diastolic (E′) velocities were then measured in each segment ( Figure 1 ). From these intervals, three systolic and three diastolic overlapping RV dyssynchrony indices were calculated. The first index used the average of measurements from the basal, mid, and apical segments of the RV lateral wall and IVS. The second index measured the delay between the RV lateral wall and IVS only at the basal segment. The third index calculated the SD of time to peak systolic velocity from the six RV lateral wall and IVS segments. These were calculated as follows. For systole,
- 1.
RV systolic delay (velocities) = delay between the time to peak systolic velocity averaged from the basal, mid, and apical segments of the RV lateral wall and the time to peak systolic velocity averaged from the basal, mid, and apical IVS;
- 2.
RV basal systolic delay (velocities) = delay between the time to peak systolic velocity between the basal RV lateral wall and basal IVS; and
- 3.
RV systolic dyssynchrony index (RV Ts-6) = SD of the time from QRS onset to peak systolic velocity in six RV lateral wall and IVS segments.
- 1.
RV diastolic delay (velocities) = delay between the time to peak diastolic velocity averaged from the basal, mid, and apical segments of the RV lateral wall and the time to peak diastolic velocity averaged from the basal, mid, and apical IVS;
- 2.
RV basal diastolic delay (velocities) = delay between the time to peak systolic velocity between the basal RV lateral wall and basal IVS; and
- 3.
RV diastolic dyssynchrony index (RV Td-6) = SD of the time from QRS onset to peak diastolic velocity in six RV lateral wall and IVS segments.
Two-Dimensional Speckle Tracking
Similar to the calculation of RV dyssynchrony by tissue velocities, RV systolic delay and a six-segment systolic SD were calculated by 2D speckle tracking as follows ( Figure 2 ):
- 1.
RV systolic delay (strain) = delay between the time to peak systolic strain averaged from the basal, mid, and apical segments of the RV lateral wall and the time to peak systolic strain averaged from the basal, mid, and apical IVS;
- 2.
RV basal systolic delay (strain) = delay between the time to peak systolic strain between the basal RV lateral wall and basal IVS; and
- 3.
RV systolic dyssynchrony index (strainRV Ts-6) = SD of the time from QRS onset to peak systolic strain in six RV lateral wall and IVS segments.
All indices are reported as the average of three measurements with and without correction for heart rate (RV delay/R-R interval × 100%).
Interobserver and Intraobserver Variability
Images from 20 randomly selected subjects were analyzed twice by the same observer at an interval of >4 weeks for intraobserver variability and by two independent observers for interobserver variability.
Statistical Analysis
RV synchrony parameters (RV systolic and diastolic delays and RV dyssynchrony indices) are expressed as mean ± SD. The independent-samples t test was used to test differences in RV synchrony parameters between male and female subjects. A paired-samples test was used to test the difference between DTI-derived RV systolic and diastolic synchrony parameters. Associations between age and RV synchrony parameters and between RV systolic and diastolic synchrony parameters (velocities) were tested using Pearson’s correlation coefficient. Linear regression was used to investigate the relation of time to peak strain between the RV lateral wall and IVS. To evaluate the RV synchrony parameters at different ages, children were divided into age ranges. Intraobserver and interobserver variability were assessed using Bland-Altman analysis. A P value < .05 was taken as indicating statistical significance. SPSS version 13 (SPSS, Inc., Chicago, IL) was used for statistical analysis.
Results
Population and Feasibility
One hundred three children were studied. Their characteristics are shown in Table 1 . DTI analysis was feasible in 98 children (95%; four were excluded for inadequate RV visualization and one for poor image quality). Two-dimensional speckle-tracking analysis was feasible in 65 children (63%; 26 were excluded for inadequate RV visualization and 12 for poor tracking). Overall, when adequate RV images were available, DTI was feasible in 99% of subjects and 2D speckle tracking in 84%. Frame rates were 166 ± 48 frames/sec for DTI and 73 ± 23 frames/sec for 2D speckle tracking.
| Variable | Value |
|---|---|
| Age (years) | 12 (3–18) |
| Gender | |
| Female | 51 (49.5%) |
| Male | 52 (50.5%) |
| Heart rate (beats/min) | 70 (43–124) |
| Height (cm) | 152 (94–183) |
| Weight (kg) | 42 (12–92) |
| Body mass index (kg/m 2 ) | 18.3 (13.9–30) |
| Body surface area (m 2 ) | 1.32 (0.57–2.16) |
RV Systolic and Diastolic Delays and RV Dyssynchrony Indices in Normal Children
RV delays and RV dyssynchrony indices for systole and diastole stratified by age group are shown in Table 2 . The mean ± 2 SDs for the RV delay by any method was <70 msec or <8% of the cardiac cycle for systole and <65 msec or <7% of the cardiac cycle for diastole, while the RV dyssynchrony index was <45 msec in systole and <40 msec in diastole. Time to peak systolic strain at the RV lateral wall (average of three segments) correlated closely with time to peak systolic strain at the IVS (average of three segments) ( Figure 3 ).
| Variable | All subjects | 3–5 years | 6–10 years | 11–14 years | 15–18 years |
|---|---|---|---|---|---|
| DTI ( n ) | 98 | 23 | 19 | 29 | 27 |
| RV systolic delay (entire wall) (ms) | 8 ± 23 | 5 ± 17 | −7 ± 14 | 14 ± 25 | 14 ± 26 |
| Heart rate corrected (%) | 0.9 ± 2.7 | 0.6 ± 2.4 | −0.9 ± 1.9 | 1.6 ± 3 | 1.6 ± 2.6 |
| RV systolic delay (basal segments) (ms) | 12 ± 29 | 8 ± 23 | −8 ± 21 | 20 ± 33 | 20 ± 28 |
| Heart rate corrected (%) | 1.4 ± 3.4 | 1 ± 2.9 | −0.9 ± 2.9 | 2.3 ± 3.9 | 2.2 ± 3 |
| Systolic RV-SD(6) (ms) | 18 ± 10 | 15 ± 8 | 15 ± 8 | 19 ± 12 | 21 ± 11 |
| Heart rate corrected (%) | 2.1 ± 1.2 | 2.2 ± 1.1 | 1.8 ± 1 | 2.2 ± 1.4 | 2.2 ± 1.2 |
| RV diastolic delay (entire wall) (ms) | 21 ± 17 | 14 ± 16 | 22 ± 11 | 26 ± 14 | 22 ± 20 |
| Heart rate corrected (%) | 2.5 ± 2 | 1.9 ± 2.2 | 2.7 ± 1.5 | 2.9 ± 1.8 | 2.3 ± 2.2 |
| RV diastolic delay (basal segments) (ms) | 23 ± 22 | 15 ± 19 | 20 ± 23 | 30 ± 21 | 23 ± 24 |
| Heart rate corrected (%) | 2.7 ± 2.7 | 2.2 ± 3 | 2.5 ± 3.1 | 3.4 ± 2.6 | 2.4 ± 2.5 |
| Diastolic RV-SD(6) (ms) | 18 ± 8 | 14 ± 7 | 16 ± 5 | 18 ± 7 | 22 ± 9 |
| Heart rate corrected (%) | 2.1 ± 0.9 | 2.2 ± 1 | 1.9 ± 0.7 | 2.1 ± 0.9 | 2.3 ± 1 |
| 2D speckle tracking ( n ) | 65 | 15 | 13 | 19 | 18 |
| RV systolic delay (entire wall) (ms) | 16 ± 17 | 16 ± 11 | 10 ± 14 | 14 ± 16 | 23 ± 23 |
| Heart rate corrected (%) | 1.9 ± 2 | 2.3 ± 1.5 | 1.2 ± 1.7 | 1.6 ± 1.9 | 2.4 ± 2.4 |
| RV systolic delay (basal segments) (ms) | 28 ± 29 | 30 ± 21 | 12 ± 29 | 33 ± 32 | 33 ± 30 |
| Heart rate corrected (%) | 3.4 ± 3.5 | 4.5 ± 3.3 | 1.4 ± 3.8 | 3.7 ± 3.6 | 3.5 ± 3.2 |
| Systolic RV-SD(6) (ms) | 20 ± 9 | 14 ± 6 | 21 ± 8 | 20 ± 10 | 23 ± 11 |
| Heart rate corrected (%) | 2.3 ± 1.1 | 2.2 ± 1 | 1.9 ± 0.7 | 2.1 ± 0.9 | 2.3 ± 1 |
Influence of Gender and Age on RV Synchrony
RV delays and RV dyssynchrony indices were not different between male and female subjects. Age was weakly associated with RV systolic delay (velocities) ( r = 0.20, P = .049) and RV diastolic delay (velocities) ( r = 0.20, P = .021). These associations were lost when corrected for heart rate. Age also had weak correlations with the RV systolic dyssynchrony index measured by tissue velocities ( r = 0.24, P = .018) or strain ( r = 0.20, P = .06).
Comparison of DTI Systolic and Diastolic RV Synchrony
RV systolic delay (velocities) was shorter than RV diastolic delay (velocities), with 8 msec or 0.9% of the cardiac cycle for systole and 21 msec or 2.5% of the cardiac cycle for diastole ( P < .001). There were no significant associations between RV systolic and diastolic delays (velocities). There was no significant difference between RV systolic and diastolic dyssynchrony indices measured by tissue velocities.
Intraobserver and Interobserver Variability
Intraobserver and interobserver variability for RV delays and RV dyssynchrony indices by DTI velocities and 2D strain are shown in Table 3 and in Figures 4 and 5 . The mean absolute difference between observers was low (<10 msec for RV delay), but with high variability, likely related at least in part to the RV delay spanning from negative to positive across the zero line depending on whether the lateral wall contracted before or after the IVS.
