Ventricular dyssynchrony late after the Fontan operation is associated with decreased survival.

BACKGROUND: Ventricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation. METHODS: Single-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and an age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death, heart transplant or heart transplant listing (D/HTx). RESULTS: A total of 503 cases (15 y; IQR 10, 21) and 42 controls (16 y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx. CONCLUSIONS: Compared to control LVs, single right and mixed morphology ventricles in the Fontan circulation exhibit a higher degree of mechanical dyssynchrony as evaluated by CMR-FT. Dyssynchrony indices correlate with ventricular size and function and are associated with death or need for heart transplantation. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation.

Transcatheter Ductus Arteriosus Stenting for Acute Pediatric Pulmonary Arterial Hypertension is Associated with Improved Right Ventricular Echocardiography Strain.

BACKGROUND: Interventional therapies for severe pulmonary arterial hypertension (PAH) can provide right ventricular (RV) decompression and preserve cardiac output. Transcatheter stent placement in a residual ductus arteriosus (PDA) is one potentially effective option in critically ill infants and young children with PAH. We sought to assess recovery of RV function by echocardiographic strain in infants and young children following PDA stenting for acute PAH. METHODS: Retrospective review of patients < 2 years old who underwent PDA stenting for acute PAH. Clinical data were abstracted from the electronic medical record. RV strain (both total and free wall components) was assessed from echocardiographic images at baseline and 3, 6, and 12 months post-intervention, as well as at last echocardiogram. RESULTS: Nine patients underwent attempted ductal stenting for PAH. The median age at intervention was 38 days and median weight 3.7 kg. One-third (3of 9) of patients had PAH associated with a congenital diaphragmatic hernia. PDA stents were successfully deployed in eight patients. Mean RV total strain was - 14.9 ± 5.6% at baseline and improved to - 23.8 ± 2.2% at 6 months post-procedure (p < 0.001). Mean free wall RV strain was - 19.5 ± 5.4% at baseline and improved to - 27.7 ± 4.1% at 6 months (p = 0.002). Five patients survived to discharge, and four patients survived 1 year post-discharge. CONCLUSION: PDA stenting for severe, acute PAH can improve RV function as assessed by strain echocardiography. The quantitative improvement is more prominent in the first 6 months post-procedure and stabilizes thereafter.

A multicenter study of three-dimensional echocardiographic evaluation of normal pediatric left ventricular volumes and function.

BACKGROUND: Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function. METHODS: Six hundred and ninety-eight healthy children (ages 0-18 years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor-independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA)-based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC). RESULTS: Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV was 0.99, 0.99, and 0.99, respectively. The ICC for interobserver variability for EDV, ESV, and SV was 0.98, 0.94, and 0.98, respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42). CONCLUSIONS: We report pediatric z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.

Cardiac resynchronization therapy improves the ventricular function of patients with Fontan physiology.

Past studies have not detected consistent improvement in ventricular function (VFxn) following initiation of cardiac resynchronization therapy (CRT) in Fontan patients. However, these studies used qualitative assessments of VFxn and/or quantitative assessments of VFxn that rely upon anatomic and/or geometric assumptions that may not be valid in patients with single ventricles. To address this, we used quantitative indices of global VFxn (dP/dtic and the Tei index) that are not encumbered by the limitations associated with the indices used in previous studies of CRT in Fontan patients. METHODS: Patients with Fontan physiology who had received CRT therapy from 2004 to 2019 were included in the study. They were compared to a concurrent group of Fontan patients who had received standard dual-chamber pacemakers (DCPMs). RESULTS: VFxn was assessed at 3 time points: prior to, shortly after, and late after initiation of pacemaker therapy. Prior to initiation of pacemaker therapy, VFxn of the CRT patients tended to be worse than that of the DCPM patients. For both groups, VFxn appeared to be stable or slightly improved shortly after initiation of pacemaker therapy. In the CRT group, VFxn improved significantly between early and late follow-up. In contrast, VFxn in DCPM patients tended to decline during this period. Changes in VFxn correlated with concurrent changes in New York Heart Association classification. CONCLUSIONS: Quantitative assessments of VFxn using indices not confounded by complex cardiac anatomy, segmental wall motions abnormalities, or inappropriate geometric assumptions revealed that CRT in Fontan patients is associated with preservation or improvement VFxn compared to standard DCPM. Changes in VFxn correlate with concurrent changes in New York Heart Association classification.

Speckle tracking echocardiographically-based analysis of ventricular strain in children: an intervendor comparison.

BACKGROUND: Strain and synchrony can be calculated from a variety of software packages, but there is a paucity of data with inter-vendor comparisons in children. To test the hypothesis that different packages may affect results, independent of acquisition, we compared values obtained using two commercially available analysis tool (QLAB and TomTec), with several different settings. METHODS: The study population included 108 children; patients were divided into three groups: (1) normal cardiac structure and conduction; (2) ventricular paced rhythm; and (3) flattened ventricular septum (reflecting right ventricular pressure or volume load lesions). We analyzed the same image acquired from the apical 4-chamber (AP4) and short-axis at the mid-papillary level (SAXM) views in both QLAB (versions 10.5 and 10.8) and TomTec (version 1.2). In QLAB version 10.8, low, medium, and high quantification smoothness settings were employed. In TomTec, images were analyzed with both low and high frame rates. Tracking quality for each package was graded. AP4 and SAXM strain and synchrony values were recorded. A mixed-effects linear regression model was used, with main effect considered significant if the p-value was < 0.05. RESULTS: Tracking scores were high for all packages except QLAB 10.5 in the SAXM view. AP4 and SAXM strain values varied significantly between QLAB 10.5 and the other packages. Synchrony values varied widely for all strain values (p < 0.001 for both) in all packages. Quantification smoothness changes in QLAB 10.8 did not impact strain significantly in any patient group; temporal resolution changes in TomTec resulted in strain differences in children with flat ventricular septums, but not those with normal or ventricular paced hearts. CONCLUSION: Synchrony values varied substantially among all packages in children. Strain values varied widely between QLAB 10.5 and all other software packages, recommending avoidance of QLAB 10.5 for future studies. Quantification smoothness settings in QLAB 10.8 resulted in minimal strain differences. In TomTec, low and high frame rate strain values differed only in a subset of patients (flattened septum). These data suggest that reliable comparisons between strain values derived from QLAB and TomTec is possible in certain cases, but that caution should be used especially in different hemodynamics conditions.

Impact of Pregnancy on Ventricular Strain in Women with Repaired Tetralogy of Fallot.

Increasing numbers of women with repaired tetralogy of Fallot (rTOF) are reaching reproductive age and seek counseling regarding their cardiovascular risks related to pregnancy. Therefore, the aim of this study was to characterize changes in left ventricular (LV) strain in women with rTOF during pregnancy and in the postpartum period. Seventeen pregnancies in women with rTOF were included (mean age at repair = 3.2 years ± 5.5 years; mean age at delivery = 32.7 ± 4 years). Echocardiograms from three time periods were analyzed; baseline (prior to conception or in the first trimester), third trimester, and 4-6 weeks postpartum. Sixty-five percent of the patients had at least mild pulmonary regurgitation. Eight patients (47%) had undergone at least one pulmonary valve replacement. There were no changes in LV ejection fraction (EF) or circumferential strain across the three time periods. Significant differences were present in longitudinal strain within the three time points (p = 0.01). Postpartum strain decreased in magnitude compared to the third trimester value (- 17.7 ± 4.1 vs. - 21 ± 5, p-value = 0.003) but was not different when compared to baseline strain (- 17.7 ± 4.1 vs. - 19.4 ± 3.4; p-value = 0.15). In conclusion, in women with rTOF, changes in longitudinal strain were observed during pregnancy with a return to baseline after delivery; EF did not change. These findings provide evidence that pregnancy does not adversely impact LV mechanics in the short term in this potentially vulnerable patient population.

Impact of surgical pulmonary valve replacement on ventricular strain and synchrony in patients with repaired tetralogy of Fallot: a cardiovascular magnetic resonance feature tracking study.

BACKGROUND: In patients with repaired tetralogy of Fallot (TOF), a better understanding of the impact of surgical pulmonary valve replacement (PVR) on ventricular mechanics may lead to improved indications and outcomes. Therefore, we used cardiovascular magnetic resonance (CMR) feature tracking analysis to quantify ventricular strain and synchrony in repaired TOF patients before and after PVR. METHODS: Thirty-six repaired TOF patients (median age 22.4 years) prospectively underwent CMR a mean of 4.5 ± 3.8 months before PVR surgery and 7.3 ± 2.1 months after PVR surgery. Feature tracking analysis on cine steady-state free precession images was used to measure right ventricular (RV) and left ventricular (LV) circumferential strain from short-axis views at basal, mid-ventricular, and apical levels; and longitudinal strain from 4-chamber views. Intraventricular synchrony was quantified using the maximum difference in time-to-peak strain, the standard deviation of the time-to-peak, and cross correlation delay (CCD) metrics; interventricular synchrony was assessed using the CCD metric. RESULTS: Following PVR, RV end-diastolic volume, end-systolic volume, and ejection fraction declined, and LV end-diastolic volume and end-systolic volume both increased with no significant change in the LV ejection fraction. LV global basal and apical circumferential strains, and basal synchrony improved. RV global circumferential and longitudinal strains were unchanged, and there was a varied impact on synchrony across the locations. Interventricular synchrony worsened at the midventricular level but was unchanged at the base and apex, and on 4-chamber views. CONCLUSIONS: Surgical PVR in repaired TOF patients led to improved LV global strain and no change in RV global strain. LV and RV synchrony parameters improved or were unchanged, and interventricular synchrony worsened at the midventricular level.

Impact of the cone operation on left ventricular size, function, and dyssynchrony in Ebstein anomaly: a cardiovascular magnetic resonance study.

BACKGROUND: In addition to tricuspid regurgitation (TR) and right ventricular (RV) enlargement, patients with Ebstein anomaly are at risk for left ventricular (LV) dysfunction and dyssynchrony. We studied the impact of the cone tricuspid valve reconstruction operation on LV size, function, and dyssynchrony. METHODS: All Ebstein anomaly patients who had both pre- and postoperative cardiovascular magnetic resonance (CMR) studies were retrospectively identified. From cine images, RV and LV volumes and ejection fractions (EF) were calculated, and LV circumferential and longitudinal strain were measured by feature tracking. To quantify LV dyssynchrony, temporal offsets (TOs) were computed among segmental circumferential strain versus time curves using cross-correlation analysis and patient-specific reference curves. An LV dyssynchrony index was calculated as the standard deviation of the TOs. RESULTS: Twenty patients (65% female) were included with a median age at cone operation of 16 years, and a median time between pre- and postoperative CMR of 2.8 years. Postoperatively, there was a decline in the TR fraction (56 ± 19% vs. 5 ± 4%, p < 0.001), RV end-diastolic volume (EDV) (242 ± 110 ml/m2 vs. 137 ± 82 ml/m2, p < 0.001), and RV stroke volume (SV) (101 ± 35 vs. 51 ± 7 ml/m2, p < 0.001). RV EF was unchanged. Conversely, there was an increase in both LV EDV (68 ± 13 vs. 85 ± 13 ml/m2, p < 0.001) and LV stroke volume (37 ± 8 vs. 48 ± 6 ml/m2, p < 0.001). There was no change in LV EF, or global circumferential and longitudinal strain but basal septal circumferential strain improved (16 ± 7% vs. 22 ± 5%, p = 0.04). LV contraction become more synchronous (dyssynchrony index: 32 ± 17 vs. 21 ± 9 msec, p = 0.02), and the extent correlated with the reduction in RV EDV and TR. CONCLUSIONS: In patients with the Ebstein anomaly, the cone operation led to reduced TR and RV stroke volume, increased LV stroke volume, improved LV basal septal strain, and improved LV synchrony. Our data demonstrates that the detrimental effect of the RV on LV function can be mitigated by the cone operation.

Ventricular strain in fetuses with aortic stenosis and evolving hypoplastic left heart syndrome before and after prenatal aortic valvuloplasty.

OBJECTIVE: The impact of prenatal intervention on fetal cardiac function has not been well defined. We assessed standard ventricular function parameters and strain in fetuses with evolving hypoplastic left heart syndrome (HLHS) treated with fetal aortic valvuloplasty (fAVP). METHODS: Fetuses with valvar aortic stenosis that underwent fAVP were studied. Echocardiographic images prior to intervention (Pre), within 1 week after fAVP (Post), and at the last prenatal follow-up examination (FU) were analyzed. Left ventricular (LV) circumferential (LVCS) and longitudinal strain (LVLS), right ventricular (RV) longitudinal strain (RVLS), and LV end-diastolic dimension Z-scores (LVIDD-Z) were documented and compared according to postnatal outcome. RESULTS: Among 57 fetuses studied, the postnatal outcome was biventricular in 23 and univentricular in 34. Prior to fAVP, strain was <4 in most cases, regardless of outcome. Biventricular fetuses had higher LVCS and LVLS segmental strain than univentricular fetuses. Among fetuses with a biventricular outcome, LVCS and LVLS increased as LVIDD-Z decreased in late gestation, whereas LVCS and LVLS remained <4 in univentricular fetuses, although the LVIDD-Z decreased to <0 in all cases. Septal RVLS increased after fAVP in the biventricular but not the univentricular outcome group. CONCLUSION: In utero aortic valve dilation appears to have a beneficial effect on both LV and RV function in some fetuses with evolving HLHS.

Evolving Role of Three-Dimensional Echocardiography for Right Ventricular Volume Analysis in Pediatric Heart Disease: Literature Review and Clinical Applications.

Accurate knowledge of right ventricular (RV) volumes and ejection fraction is fundamental to providing optimal care for pediatric patients with congenital and acquired heart disease, as well as pulmonary hypertension. Traditionally, these volumes have been measured using cardiac magnetic resonance because of its accuracy, reproducibility, and freedom from geometric assumptions. More recently, an increasing number of studies have described the measurement of RV volumes using three-dimensional (3D) echocardiography. In addition, volumes by 3D echocardiography have also been used for outcome research studies in congenital heart surgery. Importantly, 3D echocardiographic acquisitions can be obtained over a small number of cardiac cycles, do not require general anesthesia, and are less costly than CMR. The ease and safety of the 3D echocardiographic acquisitions allow serial studies in the same patient. Moreover, the studies can be performed in various locations, including the intensive care unit, catheterization laboratory, and general clinic. Because of these advantages, 3D echocardiography is ideal for serial evaluation of the same patient. Despite these potential advantages, 3D echocardiography has not become a standard practice in children with congenital and acquired heart conditions. In this report, the authors review the literature on the feasibility, reproducibility, and accuracy of 3D echocardiography in pediatric patients. In addition, the authors investigate the advantages and limitations of 3D echocardiography in RV quantification and offer a pathway for its potential to become a standard practice in the assessment, planning, and follow-up of congenital and acquired heart disease.

Euclidean and Shape-Based Analysis of the Dynamic Mitral Annulus in Children using a Novel Open-Source Framework.

BACKGROUND: The dynamic shape of the normal adult mitral annulus has been shown to be important to mitral valve function. However, annular dynamics of the healthy mitral valve in children have yet to be explored. The aim of this study was to model and quantify the shape and major modes of variation of pediatric mitral valve annuli in four phases of the cardiac cycle using transthoracic echocardiography. METHODS: The mitral valve annuli of 100 children and young adults with normal findings on three-dimensional echocardiography were modeled in four different cardiac phases using the SlicerHeart extension for 3D Slicer. Annular metrics were quantified using SlicerHeart, and optimal normalization to body surface area was explored. Mean annular shapes and the principal components of variation were computed using custom code implemented in a new SlicerHeart module (Annulus Shape Analyzer). Shape was regressed over metrics of age and body surface area, and mean shapes for five age-stratified groups were generated. RESULTS: The ratio of annular height to commissural width of the mitral valve ("saddle shape") changed significantly throughout age for systolic phases (P < .001) but within a narrow range (median range, 0.20-0.25). Annular metrics changed statistically significantly between the diastolic and systolic phases of the cardiac cycle. Visually, the annular shape was maintained with respect to age and body surface area. Principal-component analysis revealed that the pediatric mitral annulus varies primarily in size (mode 1), ratio of annular height to commissural width (mode 2), and sphericity (mode 3). CONCLUSIONS: The saddle-shaped mitral annulus is maintained throughout childhood but varies significantly throughout the cardiac cycle. The major modes of variation in the pediatric mitral annulus are due to size, ratio of annular height to commissural width, and sphericity. The generation of age- and size-specific mitral annular shapes may inform the development of appropriately scaled absorbable or expandable mitral annuloplasty rings for children.

Pediatric Normal Values and Z Score Equations for Left and Right Ventricular Strain by Two-Dimensional Speckle-Tracking Echocardiography Derived from a Large Cohort of Healthy Children.

BACKGROUND: Strain values vary with age in children and are both vendor and platform specific. Philips QLAB 10.8 and TomTec AutoSTRAIN are two widely used strain analysis platforms, and both incorporate recent European Association of Cardiovascular Imaging/American Society of Echocardiography/Industry Task Force to Standardize Deformation Imaging guidelines. The aims of this study were to establish normal strain values and Z scores for both platforms using a large data set of healthy children and to compare values among these two platforms and a previous version, QLAB 10.5, which predated the task force guidelines. METHODS: Echocardiograms from 1,032 subjects <21 years old with structurally and functionally normal hearts were included. Images were obtained on the Philips EPIQ platform. Left ventricular (LV) and right ventricular (RV) strain was analyzed using QLAB 10.8 and AutoSTRAIN, and measurement reliability was assessed. Z score equations were derived as a function of age for QLAB 10.8 (LV longitudinal and circumferential strain) and AutoSTRAIN (LV and RV longitudinal strain). A subset (n = 309) was analyzed using QLAB 10.5. Strain values were compared among the three platforms. RESULTS: For both of the newer platforms, strain varied with age, with magnitude reaching a maximum at 4 to 5 years. For LV longitudinal strain, the largest differences in value were observed in the youngest patients when using QLAB 10.5; the other two platforms were similar. LV circumferential strain measurements (QLAB 10.5 vs QLAB 10.8) were different for all ages, as were measurements of RV longitudinal strain (QLAB 10.8 vs AutoSTRAIN). Reliability was greater for AutoSTRAIN than for QLAB 10.8 and greater for LV than for RV strain. CONCLUSIONS: Normal RV and LV strain values and Z scores were generated from a large cohort of children for two commonly used platforms in pediatric echocardiography laboratories. Following the incorporation of task force guidelines, the greatest improvement in standardization was seen in infants. Small differences persist between modern platforms; however, these results support the cautious consideration of comparing interplatform measurements.

Right Heart Remodeling After Pulmonary Valve Replacement in Patients With Pulmonary Atresia or Critical Stenosis With Intact Ventricular Septum.

Background Patients with pulmonary atresia or critical pulmonary stenosis with intact ventricular septum (PA/IVS) and biventricular circulation may require pulmonary valve replacement (PVR). Right ventricular (RV) remodeling after PVR is well described in tetralogy of Fallot (TOF); we sought to investigate RV changes in PA/IVS using cardiac magnetic resonance imaging. Methods and Results A retrospective cohort of patients with PA/IVS who underwent PVR at Boston Children's Hospital from 1995 to 2021 with cardiac magnetic resonance imaging before and after PVR was matched 1:3 with patients with TOF by age at PVR. Median regression modeling was performed with post-PVR indexed RV end-diastolic volume as the primary outcome. A total of 20 patients with PA/IVS (cases) were matched with 60 patients with TOF (controls), with median age at PVR of 14 years. Pre-PVR indexed RV end-diastolic volume was similar between groups; cases had higher RV ejection fraction (51.4% versus 48.6%; P=0.03). Pre-PVR RV free wall and left ventricular (LV) longitudinal strain were similar, although LV midcavity circumferential strain was decreased in cases (-15.6 versus -17.1; P=0.001). At a median of 2 years after PVR, indexed RV end-diastolic volume was similarly reduced; cases continued to have higher RV ejection fraction (52.3% versus 46.9%; P=0.007) with less reduction in RV mass (Δ4.5 versus 9.6 g/m2; P=0.004). Post-PVR, RV and LV longitudinal strain remained unchanged, and LV circumferential strain was similar, although lower in cases. Conclusions Compared with patients with TOF, patients with PA/IVS demonstrate similar RV remodeling after PVR, with lower reduction in RV mass and comparatively higher RV ejection fraction. Although no differences were detected in peak systolic RV or LV strain values, further investigation of diastolic parameters is needed.

A comparison between the apical and subcostal view for three-dimensional echocardiographic assessment of right ventricular volumes in pediatric patients.

Background: Accurate measurement of ventricular volumes is an important clinical imaging goal. Three-dimensional echocardiography (3DEcho) is used increasingly as it is more available and less costly than cardiac magnetic resonance (CMR). For the right ventricle (RV), the current practice is to acquire 3DEcho volumes from the apical view. However, in some patients the RV may be better seen from the subcostal view. Therefore, this study compared RV volume measurements from the apical vs. the subcostal view, using CMR as a reference standard. Methods: Patients <18 years old undergoing a clinical CMR examination were prospectively enrolled. 3DEcho was performed on the day of the CMR. 3DEcho images were acquired with Philips Epic 7 ultrasound system from apical and subcostal views. Offline analysis was performed with TomTec 4DRV Function for 3DEcho images and cvi42 for CMR ones. RV end-diastolic volume and end-systolic volume were collected. Agreement between 3DEcho and CMR was assessed with Bland-Altman analysis and the intraclass correlation coefficient (ICC). Percentage (%) error was calculated using CMR as the reference standard. Results: Forty-seven patients were included in the analysis (age range 10 months to 16 years). The ICC was moderate to excellent for all volume comparisons to CMR (subcostal vs. CMR: end-diastolic volume 0.93, end-systolic volume 0.81; apical vs. CMR: end-diastolic volume 0.94, end-systolic volume 0.74).The 3DEcho mean % error vs. CMR for end-systolic volume was 25% for subcostal and 31% for apical; for end-diastolic volume it was 15% for subcostal and 16% for apical. The % error was not significantly different between apical vs. subcostal views for end-systolic and end-diastolic volume measurements. Conclusions: For apical and subcostal views, 3DEcho-derived ventricular volumes agree well with CMR. Neither echo view has a consistently smaller error when compared to CMR volumes. Accordingly, the subcostal view can be used as an alternative to the apical view when acquiring 3DEcho volumes in pediatric patients, particularly when the image quality from this window is superior.

Right ventricular contraction patterns in healthy children using three-dimensional echocardiography.

Background: The right ventricle (RV) has complex geometry and function, with motion along three separate axes-longitudinal, radial, and anteroposterior. Quantitative assessment of RV function by two-dimension echocardiography (2DE) has been limited as a consequence of this complexity, whereas newer three dimensional (3D) analysis offers the potential for more comprehensive assessment of the contributors to RV function. The aims of this study were to quantify the longitudinal, radial and anteroposterior components of global RV function using 3D echocardiography in a cohort of healthy children and to examine maturational changes in these parameters. Methods: Three-dimensional contours of the RV were generated from a cohort of healthy pediatric patients with structurally normal hearts at two centers. Traditional 2D and 3D echo characteristics were recorded. Using offline analysis of 3D datasets, RV motion was decomposed into three components, and ejection fractions (EF) were calculated (longitudinal-LEF; radial-REF; and anteroposterior-AEF). The individual decomposed EF values were indexed against the global RVEF. Strain values were calculated as well. Results: Data from 166 subjects were included in the analysis; median age was 13.5 years (range 0 to 17.4 years). Overall, AEF was greater than REF and LEF (29.2 ± 6.2% vs. 25.1 ± 7.2% and 25.7 ± 6.0%, respectively; p < 0.001). This remained true when indexed to overall EF (49.8 ± 8.7% vs. 43.3 ± 11.6% and 44.4 ± 10%, respectively; p < 0.001). Age-related differences were present for global RVEF, REF, and all components of RV strain. Conclusions: In healthy children, anteroposterior shortening is the dominant component of RV contraction. Evaluation of 3D parameters of the RV in children is feasible and enhances the overall understanding of RV function, which may allow improvements in recognition of dysfunction and assessment of treatment effects in the future.

Visualization and Quantification of the Unrepaired Complete Atrioventricular Canal Valve Using Open-Source Software.

BACKGROUND: Repair of complete atrioventricular canal (CAVC) is often complicated by residual left atrioventricular valve regurgitation. The structure of the mitral and tricuspid valves in biventricular hearts has previously been shown to be associated with valve dysfunction. However, the three-dimensional (3D) structure of the entire unrepaired CAVC valve has not been quantified. Understanding the 3D structure of the CAVC may inform optimized repair. METHODS: Novel open-source work flows were created in SlicerHeart for the modeling and quantification of CAVC valves on the basis of 3D echocardiographic images. These methods were applied to model the annulus, leaflets, and papillary muscle (PM) structure of 35 patients (29 with trisomy 21) with CAVC using transthoracic 3D echocardiography. The mean leaflet and annular shapes were calculated and visualized using shape analysis. Metrics of the complete native CAVC valve structure were compared with those of normal mitral valves using the Mann-Whitney U test. Associations between CAVC structure and atrioventricular valve regurgitation were analyzed. RESULTS: CAVC leaflet metrics varied throughout systole. Compared with normal mitral valves, the left CAVC PMs were more acutely angled in relation to the annular plane (P < .001). In addition, the anterolateral PM was laterally and inferiorly rotated in CAVC, while the posteromedial PM was more superiorly and laterally rotated, relative to normal mitral valves (P < .001). Lower native CAVC atrioventricular valve annular height and annular height-to-valve width ratio before repair were both associated with moderate or greater left atrioventricular valve regurgitation after repair (P < .01). CONCLUSIONS: It is feasible to model and quantify 3D CAVC structure using 3D echocardiographic images. The results demonstrate significant variation in CAVC structure across the cohort and differences in annular, leaflet, and PM structure compared with the mitral valve. These tools may be used in future studies to catalyze future research intended to identify structural associations of valve dysfunction and to optimize repair in this vulnerable and complex population.

Three-Dimensional Echocardiography Right Ventricular Volumes and Ejection Fraction Reference Values in Children: A North American Multicentre Study.

BACKGROUND: Three-dimensional echocardiography (3DE) evaluation of right ventricular (RV) volumes and ejection fraction (EF) is increasingly used for clinical serial assessments and management in children. This study aims to generate sex-specific reference values and z-score equations for RV volumetric parameters, independent of age and body size indices, derived from multiple populations across North America. METHODS: We prospectively recruited 455 healthy children (ages 0 to 18 years) from 5 centres. 3DE of the RV were acquired using various vendors with analyses performed offline using vendor-independent software. 3DE datasets with all walls of the RV endocardium visible were included. We reported data on RV EF, and generated z scores for end-systolic volumes (ESV), end-diastolic volumes (EDV) and stroke volume (SV). Differences between the sexes were explored. RESULTS: Of 455 3DE datasets, 312 (68%) met imaging criteria for analysis. Median age was 10.1 years (interquartile ratio [IQR]: 5.6, 14.0) with 17% being younger than 3 years of age. The mean and standard deviation for RV EDV, ESV, and SV for male and female patients were reported. We provided a downloadable z-score calculator with height and weight as independent variables to facilitate clinical utility. Although statistically significant differences between male and female RVEF was present (female 52.9 ± 3.9% vs male 51.6 ± 3.5%, P = 0.006), after adjusting for age, height, and weight, the magnitude of difference was clinically insignificant. CONCLUSIONS: Sex-specific reference values for pediatric RV volumes and EF, and z-score equations were derived from children 3DE datasets across 5 centres in North America.

Characterization of Circulating and Urinary Biomarkers in the Fontan Circulation and Their Correlation With Cardiac Imaging.

Several circulating biomarkers have been found to play a role in the surveillance and risk stratification of heart failure without congenital heart disease, but these have not been widely studied in patients with single ventricles palliated with a Fontan operation. Imaging predictors of worse outcomes in this population include ventricular dilation and dysfunction. Patients who weighed >30 kg with a Fontan circulation referred for cardiac magnetic resonance imaging were invited to participate in the study. Blood and urine samples were obtained at the time of imaging and multiple conventional and novel biomarkers were measured. A total of 82 patients with a median age of 18 years were enrolled. Among the novel biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T had the strongest correlation with ventricular dilation and dysfunction. NT-ProBNP >100 pg/ml has a sensitivity of 91% for the detection of significant ventricular dilation (end-diastolic volume >120 ml/body surface area1.3) and 82% for detection of ejection fraction <50%. The urinary neutrophil gelatinase-associated lipocalin-2 to creatinine ratio correlated with ejection fraction and estimated glomerular filteration rate. In conclusion, abnormalities in biomarkers of heart failure are common in ambulatory, largely asymptomatic patients with Fontan circulation. NT-ProBNP may serve as a sensitive marker for the identification of patients with significant ventricular dilation or dysfunction. Further work is needed to understand how these easily measured circulating biomarkers may be integrated into clinical care.

Dynamic Annular Modeling of the Unrepaired Complete Atrioventricular Canal Annulus.

BACKGROUND: Repair of complete atrioventricular canal (CAVC) is often complicated by atrioventricular valve regurgitation, particularly of the left-sided valve. Understanding the 3-dimensional (3D) structure of the atrioventricular canal annulus before repair may help to inform optimized repair. However, the 3D shape and movement of the CAVC annulus has been neither quantified nor rigorously compared with a normal mitral valve annulus. METHODS: The complete annuli of 43 patients with CAVC were modeled in 4 cardiac phases using transthoracic 3D echocardiograms and custom code. The annular structure was compared with the annuli of 20 normal pediatric mitral valves using 3D metrics and statistical shape analysis (Procrustes analysis). RESULTS: The unrepaired CAVC annulus varied in shape significantly throughout the cardiac cycle. Procrustes analysis visually demonstrated that the average normalized CAVC annular shape is more planar than the normal mitral annulus. Quantitatively, the annular height-to-valve width ratio of the native left CAVC atrioventricular valve was significantly lower than that of a normal mitral valve in all systolic phases (P < .001). CONCLUSIONS: The left half of the CAVC annulus is more planar than that of a normal mitral valve with an annular height-to-valve width ratio similar to dysfunctional mitral valves. Given the known importance of annular shape to mitral valve function, further exploration of the association of 3D structure to valve function in CAVC is warranted.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

BACKGROUND: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied. METHODS: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value. RESULTS: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (P=0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E (P=0.009, 3.95 [1.50]), and A velocities (P=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (P=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s' and e' velocity). CONCLUSIONS: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.