The clinical relevance of evaluating right ventricular (RV) myocardial deformation in congenital heart disease is increasingly recognized. The aim of this study was to explore, using three-dimensional (3D) speckle-tracking echocardiography, RV mechanics in terms of 3D global area strain and mechanical dyssynchrony in adults with repaired tetralogy of Fallot.
Twenty patients (12 men) aged 24.7 ± 8.6 years and 22 age-matched controls (11 men) were studied. Global RV peak area strain and area strain–derived systolic dyssynchrony index (SDI) were determined using 3D speckle-tracking echocardiography. RV end-diastolic volume and end-systolic volume, ejection fraction (EF), and pulmonary regurgitation fraction were measured in patients using cardiac magnetic resonance.
Coefficients of variation for intraobserver and interobserver measurements of RV global area strain were 6.1% and 7.9%, respectively, and those for SDI were 7.6% and 10.1%, respectively. Compared with controls, patients had significantly lower global area strain ( P = .005) and greater SDI ( P = .008). The prevalence of RV mechanical dyssynchrony (SDI > control mean + 2 SDs) in patients was 30%. In patients, global area strain correlated inversely with SDI ( r = −0.42, P = .04), RV end-diastolic volume ( r = −0.48, P = .032), and RV end-systolic volume ( r = −0.48, P = .031) and positively with EF ( r = −0.51, P = .02), while RV SDI correlated positively with RV end-systolic volume ( r = 0.55, P = .012), pulmonary regurgitation fraction ( r = 0.54, P = .031), and QRS duration ( r = 0.51, P = .022) and negatively with RV EF ( r = −0.62, P = .004). Multivariate analysis showed that RV EF (β = 0.22, P = .048) was a significant correlate of global area strain in patients.
In adults after tetralogy of Fallot repair, 3D RV deformation is impaired in association with RV dyssynchrony, volume overloading, and reduced EF.
In adults with repaired tetralogy of Fallot (TOF), regular assessment of right ventricular (RV) performance and timely intervention for its preservation are of paramount importance. Although measurement of RV volumes and ejection fraction by cardiac magnetic resonance (CMR) has been regarded as the gold standard for assessing RV function in these patients, the clinical relevance of evaluating RV myocardial deformation in congenital heart disease is increasingly recognized. In adults with systemic right ventricles after atrial switch for complete transposition of the great arteries, global longitudinal systolic strain was found to be reduced and to predict adverse clinical outcomes. In children with repaired TOF, reduced RV myocardial deformation has been shown to be associated with pulmonary regurgitation and impaired exercise tolerance.
Myocardial deformation imaging of the right ventricle in patients with TOF and other congenital heart conditions has been based primarily on Doppler tissue imaging and two-dimensional (2D) speckle-tracking echocardiography (STE). Assessment of RV mechanics by Doppler tissue imaging is nonetheless limited by angle dependence. Although 2D STE enables assessment of RV deformation principally along the right ventricle’s longitudinal axis, the through-plane motion of speckles and difficulty of assessing deformation in other dimensions remain important inherent issues.
Evaluation of myocardial strain in three dimensions has been made possible by three-dimensional (3D) STE. This new imaging modality enables tracking of out-of-plane speckle motion and simultaneous imaging of various ventricular segments on the basis of the full-volume data set. Three-dimensional STE–derived area strain, in particular, may be useful, as it is regarded as a composite parameter that integrates regional consequences of deformation in the longitudinal, circumferential, and radial dimensions. Additionally, differences in time-to-peak segmental deformation among segments can reflect synchronicity of ventricular contraction. In adults with heart failure, this technique has increasingly been used to assess left ventricular (LV) mechanics. The possibility of interrogating RV mechanics in congenital heart conditions using 3D STE has hitherto not been explored. In the present study, we aimed to explore 3D RV mechanics in terms of global area strain and mechanical dyssynchrony in adults after TOF repair.
Twenty-six adults with repaired TOF and with no significant RV outflow obstruction, as defined by Doppler-derived pressure gradients < 40 mm Hg, and absence of significant residual left-to-right shunts were recruited consecutively from the adult congenital heart clinic. Of the 26 patients, 20 (76.9%) with quality RV 3D echocardiographic data were included in the final analysis. Their clinical data were collected from the case records: demographics, age at operation, types of previous procedures, and duration of follow-up since surgical repair of TOF. Twenty-two healthy subjects were recruited as controls. These included healthy siblings of patients and adult healthy staff volunteers. The target recruitment of about 20 subjects in each group was based on a power estimation of 90% and two-sided α error of .05 to detect a difference as small as 2% in global strain with an estimated standard deviation of 2% per Kleijn et al . The body weight and height of all subjects were measured, and the body surface area and body mass index were calculated accordingly. In patients, QRS duration was determined on 12-lead surface resting electrocardiography. The institutional review board approved the study, and all subjects gave informed written consent.
3D Speckle-Tracking Echocardiographic Assessment
Transthoracic echocardiography was performed using the Artida Ultrasound System (Toshiba Medical Systems, Tokyo, Japan). Three-dimensional echocardiographic imaging was performed at the cardiac apex using a matrix-array transducer, with subjects lying in the left lateral decubitus position. Full-volume acquisition, in which four adjacent subvolumes were captured over four consecutive cardiac cycles, was performed during a breath hold. A wide sector of 90° × 90° was used to ensure inclusion of the entire RV inflow and body cavity in the 3D full-volume data set. The RV outflow could not, however, be included completely in this 3D data set. The frame rate ranged from 20 to 25 volumes/sec. All echocardiographic recordings were stored on an external hard disk for offline analysis using 3D tracking software (Advanced Cardiology Package; Toshiba Medical Systems).
On the basis of the 3D volume data-set, a five-plane evaluation that included the apical four-chamber view, two-chamber orthogonal view, and three short-axis views near the apex, at the midlevel, and at the base of the right ventricle were displayed. On the basis of these five views, the RV endocardium was traced, and its movements during cardiac systole and diastole were tracked automatically for the calculation of global and regional area strain. Area strain is defined as the percentage change in endocardial surface area during the cardiac cycle relative to end-diastolic endocardial area. Although designed for assessment of LV mechanics, the software also allows division of the right ventricle into 16 segments for assessing differences in timing of regional deformation. On the basis of the global and regional time-strain curves, the RV global peak area strain and standard deviation of the 16 segmental times to peak area strain were determined. A systolic dyssynchrony index (SDI) was calculated as the standard deviation of the 16 segmental times to peak area strain as a percentage of the RR interval as described for the left ventricle. In contrast to previously reported dedicated RV analysis software, the RV outflow was not included in the current 3D data set. The volumes of the entire right ventricle, therefore, could not be determined and compared against those obtained using CMR.
To determine the reproducibility of 3D STE–derived RV area strain and SDI, 20 subjects (10 patients and 10 controls) were selected randomly and their data sets analyzed offline at different times by the same observer (H.Y.) and two different ones (H.Y., S.L.). For each of the preselected 3D volume data sets, the same or different observers were blinded to previous measurements, and each of the data sets was measured twice.
CMR was performed in patients using a 1.5-T superconducting whole-body imager (GE Signa Horizon Echospeed; GE Medical Systems, Milwaukee, WI) with a phase-array torso coil. The time intervals between echocardiographic and CMR studies were <3 months. For baseline images, electrocardiographically triggered fast spin-echo double inversion recovery axial (automatic repetition time; echo time, 42 msec) was performed. Analysis of RV function was obtained by fast card spoiled gradient recalled cine on axial and short-axis planes, respectively. Flow analysis of the pulmonary artery was obtained using fast 2D phase contrast (flip angle, 15°; velocity encoding, 150 cm/sec) and taking a plane perpendicular to the flow direction of the RV outflow tract just above the pulmonary valve but before bifurcation. Ventricular function and flow analyses were performed using the software in Advantage Window version 4.2 (GE Medical Systems).
All data are expressed as mean ± SD. Ventricular volumes were indexed to body surface area. Absolute values of global area strain were used to facilitate presentation and interpretation. Intraobserver and interobserver variability for the measurement of RV area strain and SDI were reported as the coefficients of variation, calculated by dividing the standard deviation of the differences between measurements by the mean and expressed as a percentage. Reproducibility was further determined by calculation of absolute difference between two measurements divided by the mean and expressed as percentages and intraclass correlation coefficient. An intraclass correlation coefficient ≥ 0.75 indicates good reproducibility, 0.40 to <0.75 moderate reproducibility, and <0.40 poor reproducibility. Differences in demographic and echocardiographic parameters between patients and controls were compared using unpaired Student’s t tests. Pearson’s correlation analysis was used to assess the relationships between global area strain parameters and CMR indices. The area under the receiver operating characteristic curve was calculated to determine capability of global area strain to detect RV ejection fraction < 50%. Multiple linear regression analysis was performed to assess significant correlates of RV area strain. Two-tailed P values < .05 were considered statistically significant. All statistical analyses were performed using SPSS version 16.0 (SPSS, Inc, Chicago, IL).
The 20 patients (12 men) were aged 24.7 ± 8.6 years at the time of study. They underwent surgical repair of TOF at 4.5 ± 3.7 years. Transannular patch repair was required in 16 of the 20 patients. All patients were free of cardiac symptoms at the time of study, and none had cardiac arrhythmias. Their mean QRS duration was 152 ± 25 msec, with 17 patients (85%) having QRS durations > 120 msec. Their indexed RV end-systolic volume was 89 ± 63 mL/m 2 , RV end-diastolic volume 149 ± 79 mL/m 2 , RV ejection fraction 52 ± 11%, and pulmonary regurgitant fraction 34 ± 23%. The RV ejection fraction was >50% in 70% of the patients ( n = 14). The 22 controls (11 men) were aged 20.6 ± 7.0 years ( P = .10). Compared with controls, patients had similar body weights (53.3 ± 14.7 vs 56.5 ± 12.6 kg, P = .45) and heights (162 ± 14 vs 166 ± 9 cm, P = .19).
The measurements of reproducibility for RV global area strain and SDI measurements are summarized in Table 1 .
|Coefficient of variation||6.1%||7.9%||7.6%||10.1%|
|(Absolute difference/mean) × 100%||7.1%||9.0%||10.0%||11.7%|
|Intraclass correlation coefficient||0.85||0.76||0.96||0.95|
Figures 1 and 2 show representative 3D speckle-tracking echocardiographic analysis of RV area strain curves in a control subject and a patient, respectively. Compared with controls, the peak RV global area strain was significantly lower in patients (28.1 ± 4.4% vs 31.9 ± 3.8%, P = .005; Figure 3 A).
The SDI was significantly larger in patients than in controls (9.1 ± 2.8% vs 6.9 ± 2.2%, P = .008; Figure 3 B). On the basis of control data, RV mechanical dyssynchrony could be defined as RV SDI > 11.3% (control mean + 2 SDs). Using this definition, the prevalence of RV mechanical dyssynchrony in patients was 30% ( n = 6; 95% confidence interval, 14%–52%).
Correlates of RV 3D Area Strain and SDI
For the whole cohort and in patients, RV area strain correlated negatively with SDI ( r = −0.56, P < .001, and r = −0.42, P = .04, respectively; Figure 4 A).
In patients, RV global peak area strain correlated positively with RV ejection fraction ( r = 0.51, P = .02). The area under the receiver operating characteristic curve for using 3D global area strain to detect RV ejection fraction < 50% was 0.78 (95% confidence interval, 0.58–0.99; Figure 4 B). The best cutoff point for area strain was 24.4%, which had sensitivity of 92.3% and specificity of 71.4%. On the other hand, RV global area strain correlated negatively with RV end-diastolic ( r = −0.48, P = .032) and end-systolic ( r = −0.48, P = .031) volumes and QRS duration ( r = −0.47, P = .039).
RV SDI in patients correlated positively with RV end-systolic volume ( r = 0.55, P = .012), RV ejection fraction ( r = −0.62, P = .004), pulmonary regurgitation fraction ( r = 0.54, P = .031), and QRS duration ( r = 0.51, P = .022) but not with RV end-diastolic volume ( P > .05).
Multiple linear regression analysis identified RV ejection fraction as the only significant correlate of global peak area strain (β = 0.22, P = .048) after adjustment for age at study, sex, RV end-diastolic and end-systolic volumes, RV ejection fraction, pulmonary regurgitant fraction, SDI, and QRS duration.