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Purpose: Right atrial volume (RAV) and function have proven prognostic value in the assessment of cardiac disease and may be more accurately assessed using three-dimensional echocardiography (3DE). Normal 3DE reference values for the right atrial (RA) volume and function in healthy children have not yet been published. Furthermore, current methods of indexing cardiac measurements to body surface area (BSA) alone may be insufficient. We aimed to develop reference values for 3DE-derived RAV and function in the pediatric population, to provide a comparison of regression methods using BSA, height, weight, and sex, and to compare 3DE values to two-dimensional echocardiography (2DE) derived volumes., Methods: We retrospectively analyzed 187 3DE datasets acquired for a multi-center study on healthy children at two international centers. 3DE volumes were measured with vendor-agnostic software (Tomtec), and 2DE endo-diastolic volume (EDV) using the area-length single-plane approach. Regression curve-fitting of height (Ht), weight (Wt), BSA, and sex were explored to optimize Pearson coefficient and homoscedasticity., Results: The relationship of 3DE RAVs to BSA alone was heteroscedastic, with a residual positive relationship on indexing (R 2 = 0.2506). Optimal regression of Ln (Volume) = b0 + x*Ln (Ht) + y*Ln (Wt) + z*Sex was homoscedastic. Total RA emptying fraction (EF) did not vary across age or sex, however active and passive emptying was best fit by a spline curve with a knot at approximately BSA = 1 m 2 . Strong agreement with 2DE-derived EDV was present (r 2 = 0.83)., Conclusion: We provide reference values for RA size and function in the pediatric population and provide a comparison of methods for indexing these values., (© 2024 The Author(s). Echocardiography published by Wiley Periodicals LLC.)

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., (Published by Elsevier Inc.)

Background: Three-dimensional echocardiography (3DE) is an emerging method for volumetric cardiac measurements; however, few vendor-neutral analysis packages exist. Ventripoint Medical System Plus (VMS3.0+) proprietary software utilizes a validated Magnetic resonance imaging (MRI) database of normal ventricular and atrial morphologies to calculate chamber volumes. This study aimed to compare left ventricular (LV) and atrial (LA) volumes obtained using VMS3.0+ to Tomtec echocardiography analysis software., Methods: Healthy controls (n = 98) aged 0-18 years were prospectively recruited and 3D DICOM datasets focused on the LV and LA acquired. LV and LA volumes and ejection fractions were measured using TomTec Image Arena 3D LV analysis package and using VMS3.0+. Pearson correlation coefficients, Bland-Altman's plots, and intraclass coefficients (ICC) were calculated, along with analysis time., Results: There was a very good correlation between Ventripoint Medical System (VMS) and Tomtec LV systolic (r 2  = .88, ICC .89 [95% CI .81, .94]), and diastolic (r 2  = .88, ICC .90 [95% CI .77, .95]) volumes, and between VMS and Tomtec LA diastolic (r 2  = .75, ICC .89 [95% CI .81, .93]) and systolic (r 2  = .88, ICC .91 [95% CI .78, .96]) volumes on linear regression models. Natural log transformations eliminated heteroscedasticity, and power transformations provided the best fit. The time (mins) to analyze volumes using VMS were less than using Tomtec (LV VMS 2.3 ± .5, Tomtec 3.3 ± .8, p < .001; LA: VMS 1.9 ± .4, Tomtec 3.4 ± 1.0, p < .001)., Conclusions: There was a very good correlation between knowledge-based (VMS3.0+) and 3D (Tomtec) algorithms when measuring 3D echocardiography-derived LA and LV volumes in pediatric patients. VMS was slightly faster than Tomtec in analyzing volumetric measurements., (© 2022 Wiley Periodicals LLC.)

Objectives: The aim of this study was to evaluate the mid-term outcomes after the repair of aortic arch using a standard patch augmentation technique., Methods: The study included all patients who underwent repair of a hypoplastic/interrupted aortic arch (IAA) in a single institute from June 2012 to December 2019 by a standardized patch augmentation (irrespective of concomitant intra-cardiac lesions). End points evaluated were reintervention for arch obstruction and persistent/new-onset hypertension., Results: The study included 149 patients [hypoplastic aortic arch, n = 92 (62%), IAA, n = 9 (6%), Norwood procedure, n = 48 (32%)]. The patch material used for augmentation of the aortic arch included pulmonary homograft (n = 120, 81%), homograft pericardium (n = 18, 12%), CardioCel® (n = 9, 6%) and glutaraldehyde-treated autologous pericardium (n = 2, 1%). The median age and weight at surgery were 7 days [interquartile range (IQR) 5-17 days] and 3.5 kg (IQR 3-3.9 kg), respectively. The median follow-up was 3.27 years (IQR 1.28, 5.08), range (0.02, 8.76). Freedom from reintervention at 1, 3 and 5 years was 95% [95% confidence interval (CI) = 89%, 98%], 93% (95% CI = 86%, 96%) and 93% (95% CI = 86%, 96%) respectively. One patient (0.6%) had persistent hypertension 8 years after correction for interrupted arch with truncus arteriosus., Conclusions: Repair of hypoplastic/IAA by transection and excision of all ductal tissue and standardized patch augmentation provide good mid-term durability. The freedom from reintervention at 5 years is >90%. The incidence of persistent systemic hypertension following arch reconstruction is low. The technique is reproducible and applicable irrespective of underlying arch anatomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Tricuspid regurgitation (TR) in hypoplastic left heart syndrome (HLHS) is associated with morbidity and mortality. TR mechanisms and the impact of tricuspid valve repair (TVR) are unclear. We examined HLHS TR mechanisms, TVR's impact on tricuspid valve (TV), and features of poor TVR durability., Methods: We retrospectively compared 35 HLHS TVR cases and 35 age/stage-matched HLHS controls who do not undergo TVR. Pre-operative 3-dimensional echocardiography (3DE) assessed overall TV morphology (prolapse, normal, tethered), leaflet morphology, vena contracta area, and TR location. Two-dimensional echocardiography measured TV annulus diameter, RV fractional area change (RVFAC), sphericity, and TR grade at three time points (pre-op, early post-op, and latest follow-up)., Results: Pre-op, TVR group, and controls had no difference in age, RV function or shape, or TV dimension. TVR group most commonly had anterior leaflet prolapse followed by septal leaflet prolapse or tethering. TR jet arises centrally (63%) and anterior septally (26%). Posterior annuloplasty (69%), commissuroplasty (37%), and leaflet repair (37%) were surgical techniques commonly performed. At early post-op, TR grade and TV annulus decreased. At latest follow-up, TV annulus remained reduced; however, 50% had significant TR. 25% required TV reoperation. Larger vena contracta at TVR was associated with significant TR., Conclusion: HLHS patients undergoing TVR had more anterior leaflet prolapse and central TR. While TVR initially reduces annular size and TR grade, 50% redevelop significant TR despite maintained annular reduction. The association of greater TR severity prior to repair with post-op recurrence raises the consideration for earlier repair of TR in HLHS patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Branch pulmonary artery (PA) stenosis due to ductus arteriosus (DA) tissue (DA-PS) contributes to the morbidity associated with pulmonary atresia (PAtr). We sought to identify preoperative echocardiographic features predictive of DA-PS. Patients consecutively encountered with PAtr and a DA-dependent pulmonary circulation at birth who underwent intervention in our program over a 5-year period were identified and records reviewed. Preoperative echocardiograms were reviewed to identify features that predicted postoperative DA-PS. Seventy patients with PAtr met inclusion criteria and 36 (51%) had DA-PS. At preoperative echocardiography, the proximal diameter of the PA ipsilateral to the DA was smaller in those with versus without DA-PS (Z-score - 4.8 ± 1.7 vs - 1.1 ± 1.7, respectively p < 0.001). PA origins could not be imaged on the same axial plane in 21/36 (58%) with versus 2/34 (6%) without DA-PS. Patients with DA-PS had an obtuse posterior angle of the PA bifurcation compared to those without (128 ± 17° and 87 ± 21°, p < 0.001), and a posterior angle of > 100° best predicted DA-PS with a sensitivity of 97% and specificity of 76%. An abnormal PA relationship and/or an obtuse posterior bifurcation angle had a sensitivity, specificity, positive and negative predictive value for DA-PS of 78%, 94%, 90% and 86%, respectively. Finally, DA insertion was into the ipsilateral PA in 26/36 (72%) of cases with DA-PS. A smaller proximal ipsilateral PA diameter, inability to image the PAs in the same plane, a posterior PA bifurcation angle of > 100°, and insertion of the DA in the ipsilateral PA demonstrated by echo are useful in identifying patients at risk for DA-PS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tricuspid valve regurgitation (TR) is a risk factor for morbidity and mortality in children with hypoplastic left heart syndrome (HLHS). Surgical tricuspid valve (TV) repair is common, but durable repair remains challenging. The aim of this study was to examine mechanisms of TR requiring surgery, features associated with unsuccessful repair, and TV changes after surgical repair., Methods: Thirty-six patients with HLHS requiring TV repair (TVR) and 36 matched control subjects with HLHS were assessed using two-dimensional and three-dimensional echocardiography. Using three-dimensional echocardiography, TV coordinates from the annulus, leaflet, and ventricle were used to measure annular, leaflet, prolapse, and tethering values and anterior papillary muscle angle. TR grade and ventricular size, function, and shape were assessed using two-dimensional echocardiography., Results: Patients requiring TVR had greater total leaflet prolapse, larger TV annular and leaflet areas, and flatter annuli, with no difference in tethering, coaptation index, or anterior papillary muscle angle. In patients with HLHS, successful TVR at follow-up (58%) was associated with preoperative total leaflet prolapse (especially posterior). Unsuccessful repair was associated with preoperative tethering of the septal leaflet. TVR in patients with HLHS caused a reduction of total annular and leaflet size and reduced prolapse and tethering of the posterior leaflet but did not affect anterior leaflet prolapse or septal leaflet tethering., Conclusions: Features associated with TVR include a flattened and dilated TV annulus with leaflet prolapse. The additional presence of a tethered septal leaflet before TVR is associated with significant postoperative TR. Current surgical techniques, predominantly posterior annuloplasty and commissuroplasty, adequately address annular size and posterior leaflet pathology, but not septal leaflet tethering. Individualized and innovative surgical techniques are vital to improve surgical repair success., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Twenty-five percent of patients with hypoplastic left heart syndrome (HLHS) require tricuspid valve (TV) repair. The location of tricuspid regurgitation (TR) is important in determining the type of repair performed. Studies using three-dimensional echocardiography (3DE) have reported a high incidence of error on two-dimensional echocardiography (2DE) for the identification of TV leaflets. The aim of this study was to compare assessment of TR on 3DE and 2DE in patients with HLHS (jet location, TR grade, and reproducibility)., Methods: A retrospective, single-center review was performed. Fifty-six patients with HLHS with available two-dimensional and three-dimensional echocardiograms, and mild or greater TR, were included. TR location, grade, vena contracta area, and TV annular diameter were measured on 2DE and 3DE. Reproducibility was assessed by blinded reviewers., Results: Three-dimensional echocardiography identified the primary jet location as central (57%) followed by anteroseptal (36%). There was poor agreement between findings on 3DE and 2DE for jet location (κ = 0.05; 95 CI, -0.08 to 0.19). Interobserver reproducibility for location on 3DE was excellent (κ = 0.8), whereas reproducibility for 2DE was poor (κ = 0.32). The most common jet location pre-Norwood and pre-Glenn was central (70%), whereas pre-Fontan and post-Fontan, jet location was central (45%) and anteroseptal (48%). Vena contracta area on 2DE correlated moderately with vena contracta area on 3DE (r = 0.60, P < .0001). TV annular diameters on 2DE and 3DE for lateral (r = 0.85, P < .0001) and anteroposterior (r = 0.74, P = .001) dimensions were strongly correlated., Conclusions: In children with HLHS, assessment of TR location on 2DE had poor agreement with assessment on 3DE and was poorly reproducible. In contrast, TR jet location on 3DE was highly reproducible. Pre-Glenn, a central TR jet was the most common, while post-Glenn, central and anteroseptal locations were equal, highlighting the importance of preoperative identification of TR jet location in patients with HLHS., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., (© 2021 Wiley Periodicals LLC.)

Right ventricular (RV) remodeling in hypoplastic left heart syndrome (HLHS) begins prenatally and continues through staged palliations. However, it is unclear if the most marked observed remodeling post-Norwood is secondary to cardiopulmonary bypass (CPB) exposure or if it is an adaptation intrinsic to the systemic RV. This study aims to determine the impact of CPB on RV remodeling in HLHS. Echocardiograms of HLHS survivors undergoing stage 1 Norwood (n = 26) or Hybrid (n = 20) were analyzed at pre- and post-stage 1, pre- and post-bidirectional cavo-pulmonary anastomosis (BCPA), and pre-Fontan. RV fractional area change (FAC), vector velocity imaging for longitudinal & derived circumferential deformation (global radial shortening (GRS) = peak radial displacement/end-diastolic diameter), and deformation ratio (longitudinal/ circumferential) were assessed. Both groups had similar age, clinical status and functional parameters pre-stage 1. No difference in RV size and sphericity at any stage between groups. RVFAC was normal (> 35%) throughout for both groups. Both Norwood and Hybrid patients had increased GRS (p = 0.0001) post-stage 1 and corresponding unchanged longitudinal strain, resulting in decreased deformation ratio (greater relative RV circumferential contraction), p = 0.0001. Deformation ratio remained decreased in both groups in subsequent stages. Irrespective of timing of the first CPB exposure, both Norwood and Hybrid patients underwent similar RV remodeling, with relative increase in circumferential to longitudinal contraction soon after stage 1 palliation. The observed RV remodeling in HLHS survivors were minimally impacted by CPB.

Background: Fetal Ebstein's anomaly and tricuspid valve dysplasia (EA/TVD) are associated with high perinatal mortality relative to pulmonary atresia with intact ventricular septum (PAIVS), despite both requiring redistribution of the cardiac output (CO) to the left ventricle (LV). LV dysfunction is suspected to contribute to adverse outcomes in EA/TVD., Objective: We sought to examine global and segmental LV function in fetal EA/TVD with comparison to normal controls and PAIVS. We hypothesized that LV dysfunction in EA/TVD is associated with abnormal LV remodeling and interventricular mechanics., Methods: We retrospectively identified 63 cases of fetal EA/TVD (40 with retrograde ductal flow) and 22 cases of PAIVS encountered from 2004 to 2015 and compared findings to 77 controls of comparable gestational age. We measured the combined CO and global LV function using two-dimensional, Doppler-derived, deformational (six-segmental vector velocity imaging) and dyssynchrony indices (DIs; SD of time to peak), and a novel global DI., Results: EA/TVD fetuses demonstrated abnormal LV global systolic function with reduced ejection fraction, fractional area change, and CO, while in PAIVS we observed a normal ejection fraction, fractional area change, and CO. PAIVS, but not EA/TVD, demonstrated increased LV sphericity, suggestive of remodeling, and associated enhanced radial function in the third trimester. In contrast, while EA/TVD fetuses had normal LV segmental longitudinal strain, there was abnormal radial segmental deformation and LV dyssynchrony with increased SD of time to peak and DI., Conclusions: Fetal EA/TVD is associated with a lack of spherical remodeling and presence of mechanical dyssynchrony, which likely contribute to reduced CO and ejection fraction. Clinical monitoring of LV function is warranted in fetal EA/TVD. Further studies incorporating quantification of LV function into prediction models for adverse outcomes are required., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Accurate fetal arrhythmia (FA) diagnosis is key for effective management. Currently, FA assessment relies on standard echocardiography-based techniques (M mode and spectral Doppler), which require adequate fetal position and cursor alignment to define temporal relationships of mechanical events. Few data exist on the application of color Doppler tissue imaging (c-DTI) in FA assessment. The aim of this study was to examine the feasibility and clinical applicability of c-DTI in FA assessment in comparison with standard techniques., Methods: Pregnancies with diagnosed FA were prospectively recruited to undergo c-DTI following fetal echocardiography. Multiple-cycle four-chamber clips in any orientation were recorded (mean frame rate, 180 ± 16 frames/sec). With offline analysis, sample volumes were placed on atrial (A) and ventricular (V) free walls for simultaneous recordings. Atrial and ventricular rates, intervals (for atrial-ventricular conduction and tachyarrhythmia mechanism), and relationships were assessed to decipher FA mechanism. FA diagnosis by c-DTI, conventional echocardiographic techniques, and postnatal electrocardiography and/or Holter monitoring were compared., Results: FA was assessed by c-DTI in 45 pregnancies at 15 to 39 weeks, including 16 with atrial and/or ventricular ectopic beats; 18 with supraventricular tachyarrhythmias, including ectopic atrial tachycardia in 11, atrioventricular reentrant tachycardia in four, atrial flutter in two, and intermittent atrial flutter and junctional ectopic rhythm in one; three with ventricular tachycardias; and eight with bradycardias or atrioventricular conduction pathology, including five with complete atrioventricular block (AVB), one with first-degree AVB evolving into complete AVB, one with second-degree AVB, and one with sinus bradycardia. After training, FA diagnosis by c-DTI could be made irrespective of fetal orientation within 10 to 15 min. FA diagnosis by c-DTI concurred with standard techniques in 41 cases (91%), with additional findings identified by c-DTI in 10. c-DTI led to new FA diagnoses in four cases (9%) not definable by standard techniques. FA diagnosis by c-DTI was confirmed in all 20 with persistent arrhythmias after birth, including three with new diagnoses defined by c-DTI. c-DTI was particularly helpful in deciphering SVT mechanism (long vs short ventricular-atrial interval) in all 18 cases, whereas standard techniques permitted definition in only half., Conclusions: c-DTI with offline analysis permits rapid and accurate definition of FA mechanism, providing new information in nearly one-third of affected pregnancies., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Right atrial (RA) function has been studied rarely in childhood pulmonary arterial hypertension (PAH). We sought to determine if RA and right ventricular (RV) area changes measured by echocardiography predicted outcomes., Methods: We reviewed data from children with PAH undergoing cardiac catheterization and echocardiography. RA and RV areas were obtained from the apical 4-chamber view. Clinical worsening indicated initiation of parenteral prostanoid therapy, heart and/or lung transplantation, Potts shunt surgery or death., Results: We studied 57 children (27 females), median age 3 years (range 0.30-17 years), body surface area 0.56 m2 (0.2-1.8), follow up 3 years (0.21-8.35), time to clinical worsening was 1.14 years (0.03-6.14) and mortality was 1.55 years (range 0.88-4.95). We determined from receiver operator curves that RA active emptying fraction (RA EaF) ≥60% predicted clinical worsening (sensitivity 78%, specificity 69%, AUC 0.7) and mortality (sensitivity 100%, specificity 65%, AUC 0.82). RV fractional area change (RVFAC) <25% predicted clinical worsening (sensitivity 72%, specificity 79%, AUC 0.85) and death (sensitivity 67%, specificity 69%, AUC 0.77). The combination of RA EaF ≥60% and RVFAC <33% were best predictors of clinical worsening (sensitivity 72%, specificity 82%, partial AUC 0.65) and mortality (sensitivity 100%, specificity 77%, partial AUC 0.75)., Conclusion: In childhood PAH, RA EaF ≥ 60% and RVFAC <25% were associated with poor outcomes. RA EaF ≥60% and RVFAC <33% were best predictors of clinical worsening and may be useful markers in children with PAH who require closer observation and more intensive therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Ventricular dysfunction is associated with increased morbidity and mortality in children with hypoplastic left heart syndrome. The aim of this study was to assess the diagnostic performance of conventional and speckle-tracking echocardiographic measures of right ventricular (RV) function before bidirectional cavopulmonary anastomosis palliation in predicting death or need for heart transplantation (HTx)., Methods: RV fractional area change (RVFAC) and longitudinal and circumferential strain and strain rate (SR) were measured in 64 prospectively recruited patients with hypoplastic left heart syndrome from echocardiograms obtained before bidirectional cavopulmonary anastomosis surgery. The composite end point of death or HTx was examined. Receiver operating characteristic analysis was performed, and cutoff values optimizing sensitivity and specificity were derived., Results: At a median follow-up of 5.0 years (interquartile range, 2.8-6.4 years), 13 patients meeting the composite end point had lower longitudinal strain and SR, circumferential SR, and RVFAC compared with survivors (n = 51). The conventional cutoff of RVFAC < 35% was specific for death or HTx (86%) but had poor sensitivity (46%), with an area under the curve of 0.73. Speckle-tracking echocardiographic variables showed similar areas under the curve (range, 0.69-0.79), with negative predictive values >90%. Addition of speckle-tracking echocardiographic variables to RVFAC < 35% showed no added benefit. However, in a subpopulation of patients with RVFAC ≥ 35% (n = 44), those meeting the composite end point (n = 7) had lower longitudinal SR (median, -1.0 1/sec [interquartile range, -0.8 to -1.1 1/sec] vs -1.21/sec [interquartile range, -1.0 to -1.3 1/sec], P = .03). Interobserver reproducibility was superior for longitudinal strain and SR (intraclass correlation coefficient > 0.92) compared with RVFAC (intraclass correlation coefficient = 0.75)., Conclusions: Children with hypoplastic left heart syndrome with normal RVFAC and ventricular deformation before bidirectional cavopulmonary anastomosis have a low likelihood of death or HTx in the medium term. In the presence of reduced RVFAC, speckle-tracking echocardiography does not provide additional prognostic value. However, in patients with "normal" RVFAC, it may have a role in improving outcome prediction and warrants further investigation., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Tricuspid regurgitation (TR) is an important risk factor for morbidity and mortality in hypoplastic left heart syndrome (HLHS), yet the evolution of tricuspid valve (TV) dysfunction in HLHS is poorly understood. This study sought to examine changes in TV function in HLHS between the first two stages of surgical palliation and to determine the mechanism of TR at the time of stage two surgery-bidirectional cavopulmonary anastomosis (BCPA)., Methods: We prospectively investigated 44 infants at two time points-prior to Norwood-Sano (T1 - median age 5.4 days) and prior to BCPA (T2 - median age 4.7 months) using two-dimensional (2DE) and three-dimensional echocardiography (3DE). Right ventricular (RV) size, function and shape was assessed with 2DE. Extracted spatial coordinates from 3DE were used to calculate TV leaflet and annular area, tethering and prolapse volumes, bending angle, and coaptation index. TR was graded qualitatively, and 2D and 3D vena contracta (VC) were measured., Results: The cohort from T1 to T2 had increased indexed leaflet and annular area (P < .0001) and tethering volume (P < .0001), with no change in coaptation. Significant TR was present in 14 infants (32%) at T2 and was associated with greater leaflet (P = .02) and annular areas (P = .002) and greater prolapse volume (P = .008), but not tethering volume or reduced coaptation. At latest follow-up (median 23 months), 13 patients died or required transplantation. Only 3DE VC at T2 was associated with death or transplantation., Conclusions: The TV in HLHS adapts to interstage stressors (increased preload and afterload) by increasing leaflet size to maintain adequate leaflet coaptation. Significant TR at T2 was associated with greater leaflet size and prolapse. This may represent TV maladaptation from an excessive response in leaflet expansion to stressors., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: In severe right heart obstruction (RHO), redistribution of cardiac output to the left ventricle (LV) is well tolerated by the fetal circulation. Although the same should be true of severely regurgitant tricuspid valve disease (rTVD) with reduced or no output from the right ventricle, affected fetuses more frequently develop hydrops or suffer intrauterine demise. We hypothesized that right atrium (RA) function is altered in rTVD but not in RHO, which could contribute to differences in outcomes., Methods: Multi-institutional retrospective review of fetal echocardiograms performed over a 10-year period on fetuses with rTVD (Ebstein's anomaly, tricuspid valve dysplasia) or RHO (pulmonary atresia/intact ventricular septum, tricuspid atresia) and a healthy fetal control group. Offline velocity vector imaging and Doppler measurements of RA size and function and LV function were made., Results: Thirty-four fetuses with rTVD, 40 with RHO, and 79 controls were compared. The rTVD fetuses had the largest RA size and lowest RA expansion index, fractional area of change, and RA indexed filling and emptying rates compared with fetuses with RHO and controls. The rTVD fetuses had the shortest LV ejection time and increased Tei index with a normal LV ejection fraction. RA dilation (odds ratio, 1.27; 95% CI, 1.05-1.54) and reduced indexed emptying rate (odds ratio, 2.49; 95% CI, 1.07-5.81) were associated with fetal or neonatal demise., Conclusions: Fetal rTVD is characterized by more severe RA dilation and dysfunction compared with fetal RHO and control groups. RA dysfunction may be an important contributor to reduced ventricular filling and output, potentially playing a critical role in the worsened outcomes observed in fetal rTVD., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Single right ventricles (SRV) are postulated to be disadvantaged compared with single left ventricles (SLV). We compared the evolution of SRV versus SLV function during infancy using conventional measures and speckle-tracking echocardiography (STE). We hypothesized that the SRV is mechanically disadvantaged during early infancy., Methods: SRVs (n = 32) were compared with SLVs (n = 16) at the neonatal (presurgery) and pre-bidirectional cavopulmonary anastomosis (pre-BCPA) stages. Functional measures (fractional area change, indexed ventricular annular plane systolic excursion [iVAPSE], isovolumic acceleration [IVA], myocardial performance index, E and A velocities, tissue Doppler imaging annular velocities and STE-measured global longitudinal and circumferential strain, strain rate [SR], and early diastolic SR [EDSR]) were compared between SRV and SLV at each stage and between presurgery and pre-BCPA., Results: Compared with SLV, presurgery SRV had lower circumferential strain (-10.6% vs -16.5%; P = .0002) and EDSR (1.41%/sec vs 2.13%/sec; P = .001). Pre-BCPA SRV had decreased IVA (1.2 vs 2.1 m/sec 2 ; P = .006): longitudinal strain (-15.3% vs -19.1%; P = .001), SR (-0.97%/sec vs -1.53%/sec; P = .0001), EDSR (1.5%/sec vs 2.1%/sec; P = .001); circumferential strain (-10.6% vs -14.9%; P = .002), SR (-0.8%/sec vs -1.21%/sec; P = .0001), and EDSR (1.3%/sec vs 1.8%/sec; P = .009). SRV showed reduction of iVAPSE, IVA, s', e', a' velocities, longitudinal strain, SR, EDSR, and circumferential SR (P < .05) from presurgery to pre-BCPA, while circumferential strain was unchanged. SLV showed no significant change in these parameters during this interval., Conclusions: The progressive reduction in SRV longitudinal and circumferential function suggests that SRV may have a mechanical disadvantage from birth and progressive impairment with age., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

We sought to describe the prenatal features and postnatal outcomes of the "criss-cross heart" (CCH) with crossing atrioventricular connections as encountered in 5 cases and to review the literature regarding fetal diagnoses of this lesion. We reviewed the clinical history and fetal echocardiograms of 5 patients with a diagnosis of CCH encountered in our institution from 2010 to 2015. Affected pregnancies were identified through the University of Alberta fetal cardiology database. Fetal and postnatal echocardiograms, prenatal and postnatal clinical records, autopsy, and surgical reports were reviewed. Over the past 5 years, major fetal congenital heart disease was identified in 448 pregnancies in the province of Alberta. Of these, 5 had CCH. All 5 were referred for suspected congenital heart disease, and none had significant extracardiac pathology. Detailed methodical 2-dimensional and color Doppler fetal echocardiography defined the complex diagnoses that were subsequently confirmed postnatally (n = 4) and at fetal autopsy (n = 1). Prenatal diagnosis correctly predicted postnatal presentation and outcomes in 1 with double outlet right ventricle and coarctation, 2 presenting with complete (D) transposition of the great arteries physiology, and 1 presenting as corrected (L) transposition. Three required single ventricle palliation and 1 underwent an arterial switch procedure. In conclusion, detailed evaluation of fetal CCH can result in correct anatomical and pathophysiological diagnoses. It demands a full understanding of the anatomy and pathophysiology to predict accurately the presentation at birth for accurate counseling and planning perinatal management., (Copyright © 2016. Published by Elsevier Inc.)

Echocardiography has developed as an imaging technology over 60 years to become the mainstay for investigating heart disease, providing invaluable structural and functional information. In the last 20 years, 3-dimensional echocardiography (3DE) has emerged as an adjunct to 2-dimensional echocardiography in adult and congenital heart disease. Early work with 3-dimensional imaging of the mitral valve describing normal annular shape and function significantly changed the understanding of mitral valve dynamics. Further work led to our current understanding of the mitral valve working as a unit, with all components vital to its normal function. With improving technology and ease of use, similar 3DE techniques have been used in congenital heart disease to study the unique anatomy and function of atrioventricular (AV) valves, specifically the tricuspid valve in hypoplastic left heart syndrome, and the left AV valve in atrioventricular septal defects. This paper describes the role of 3DE in assessing AV valve function in normal valves, and in congenital heart disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Significant atrioventricular valve regurgitation (AVVR) increases mortality in patients with unbalanced atrioventricular septal defects (uAVSDs) and a single ventricle. We tested the hypothesis that abnormal leaflet tethering is associated with progressive AVVR in patients with a single ventricle with uAVSD., Methods: We retrospectively reviewed the initial presentation and prebidirectional cavopulmonary anastamosis echocardiograms of 46 consecutive patients with uAVSD with single ventricle palliation. AVVR was graded as moderate to severe if the sum of vena contracta width to dominant valve annulus ratio was ≥ 0.33. We measured tenting height, annular to leaflet angle and annular diameter, indexed to patient size where appropriate. Multivariate analysis of variables to predict progressive AVVR was performed., Results: At follow-up of 3.3 ± 2.4 years, 24 patients had mild AVVR (Group A) and 22 had moderate to severe AVVR. Overall mortality was 6%, whereas 10 had valve repair/replacement surgery. Of 22 patients with severe AVVR at follow-up, 9 had severe AVVR at initial presentation (Group B), whereas 13 had mild AVVR at presentation but developed severe AVVR at their prebidirectional cavopulmonary anastamosis echocardiogram (Group C). Group A patients had a smaller tenting height at initial presentation compared with patients in Group B and Group C, and also had early progressive reduction of indexed tenting height (P < .01). An absolute tenting height >6 mm (odds ratio, 6.6; 95% confidence interval, 1.1-39.0; P = .03) at the initial echocardiogram was identified as an independent predictor of subsequent severe AVVR., Conclusions: Early leaflet tethering is predictive of subsequent AVVR in patients with a single ventricle with uAVSD. Patients with competent AVV had progressive reduction in the degree of leaflet tethering, whereas patients with AVVR did not. This may represent an important adaptive process to maintain valve competency in uAVSD., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Our purpose was to test the following hypotheses: (1) patients with hypoplastic left heart syndrome who develop significant tricuspid regurgitation (TR) or require tricuspid valve (TV) surgery in the medium term have detectable TV abnormalities by 3-dimensional echocardiography (3DE) prestage 1 palliation and (2) TR is associated with reduced survival and increased TV intervention., Methods and Results: Infants were prospectively studied with 3DE and 2DE prestage 1 and followed up for the end points of TR, TV surgery, transplantation, or death. From prestage 1 3DE, spatial coordinates of TV annulus and leaflets were extracted; annulus size, leaflet area, prolapse volume, tethering volume, bending angle, and papillary muscle angle were measured. TR was assessed prestage 1 and at latest follow-up. Of 70 patients, 62 (88.6%) had mild or less TR and 8 (11.4%) had moderate or greater TR prestage 1. Prestage 1 tethering volume correlated to leaflet area (r=0.736; P<0.001), annulus area (r=0.651; P<0.001), right ventricular end-diastolic area (r=0.347; P=0.003), fractional area change (r=-0.387; P<0.001), and TR grade (r=0.447; P<0.001). At follow-up, 46 (65.7%) had mild or less TR (group A) and 24 (34.3%) had moderate or greater TR (group B). Prestage 1 3DE showed greater TV tethering volume and flatter annulus in group B. Survival was better in group A., Conclusions: Increased TV tethering volume and flatter bending angle prestage 1 palliation is associated with TV failure at medium-term follow-up. Increased prestage 1 tethering is related to having larger TV annulus, larger leaflet area, larger right ventricular size, and reduced systolic function. TR progression results in increased TV intervention and decreased survival., (© 2014 American Heart Association, Inc.)

Background: Mechanisms of mitral valve regurgitation after atrioventricular septal defect repair are unclear., Methods: To gain further insight into mitral valve regurgitation, real-time three-dimensional echocardiography was performed in 53 patients after atrioventricular septal defect repair (30 partial and 23 complete) and 40 controls. Mitral valve {x, y, z} coordinates from the annulus, leaflet surface, papillary muscle, and chordal attachments were recorded. Vena contracta area of the regurgitant jet(s) and volume of leaflet prolapse and tethering were measured., Results: Twenty-three patients had mild (group 1) and 30 moderate (group 2) mitral valve regurgitation. Patients in both groups 1 and 2 had more circular annuli than controls. Annular area was greater in group 2 than in group 1 and controls (P < .01). Group 2 had more frequent segmental prolapse in the superior-mural leaflet segment. The anterolateral papillary muscle was more laterally displaced in group 2 than in controls and group 1 at end-diastole (P = .01 and P = .05) and formed a more acute angle with the mitral valve annulus than in controls or group 1 (P = .01)., Conclusions: In patients with atrioventricular septal defects, significant mitral valve regurgitation is associated with leaflet prolapse, larger annular area, and lateral papillary muscle displacement., (Copyright © 2012 American Society of Echocardiography. All rights reserved.)

Molecular diagnostic testing of individuals with congenital sensorineural hearing loss typically begins with DNA sequencing of the GJB2 gene. If the cause of the hearing loss is not identified in GJB2, additional testing can be ordered. However, the step-wise analysis of several genes often results in a protracted diagnostic process. The more comprehensive Hereditary Hearing Loss Arrayed Primer Extension microarray enables analysis of 198 mutations across eight genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, MTRNR1 and MTTS1) in a single test. To evaluate the added diagnostic value of this microarray for our ethnically diverse patient population, we tested 144 individuals with congenital sensorineural hearing loss who were negative for biallelic GJB2 or GJB6 mutations. The array successfully detected all GJB2 changes previously identified in the study group, confirming excellent assay performance. Additional mutations were identified in the SLC26A4, SLC26A5 and MTRNR1 genes of 12/144 individuals (8.3%), four of whom (2.8%) had genotypes consistent with pathogenicity. These results suggest that the current format of this microarray falls short of adding diagnostic value beyond the customary testing of GJB2, perhaps reflecting the array's limitations on the number of mutations included for each gene, but more likely resulting from unknown genetic contributors to this phenotype. We conclude that mutations in other hearing loss associated genes should be incorporated in the array as knowledge of the etiology of hearing loss evolves. Such future modification of the flexible configuration of the Hereditary Hearing Loss Arrayed Primer Extension microarray would improve its impact as a diagnostic tool.

Using the Hereditary Hearing Loss arrayed primer extension (APEX) array, which contains 198 mutations across 8 hearing loss-associated genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, 12S-rRNA, and tRNA Ser), we compared the frequency of sequence variants in 94 individuals with early presbycusis to 50 unaffected controls and aimed to identify possible genetic contributors. This cross-sectional study was performed at Stanford University with presbycusis samples from the California Ear Institute. The patients were between ages 20 and 65 yr, with adult-onset sensorineural hearing loss of unknown etiology, and carried a clinical diagnosis of early presbycusis. Exclusion criteria comprised known causes of hearing loss such as significant noise exposure, trauma, ototoxic medication, neoplasm, and congenital infection or syndrome, as well as congenital or pediatric onset. Sequence changes were identified in 11.7% and 10% of presbycusis and control alleles, respectively. Among the presbycusis group, these solely occurred within the GJB2 and SLC26A4 genes. Homozygous and compound heterozygous pathogenic mutations were exclusively seen in affected individuals. We were unable to detect a statistically significant difference between our control and affected populations regarding the frequency of sequence variants detected with the APEX array. Individuals who carry two mild mutations in the GJB2 gene possibly have an increased risk of developing early presbycusis.

Purpose: The GDx (Laser Diagnostic Technologies, San Diego, CA) is a scanning laser polarimeter designed to assess the peripapillary nerve fiber layer in vivo. On the GDx, a nerve fiber bundle can appear as a single or as a split bundle. The aim of our study was to determine the prevalence of split nerve fiber layer bundles and to demonstrate their clinical relevance., Design: Cross-sectional study., Participants: Two hundred fifty-four healthy volunteers participated., Methods: We imaged 454 eyes of 254 healthy white persons with the GDx. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program). According to our working definition, a bundle appeared 'split' when the color-coded pixels corresponding to areas of higher retardation were clearly divided into two more-or-less symmetrical parts not resembling a wedge defect. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification., Main Outcome Measures: The presence of a split nerve fiber layer bundle., Results: Interobserver agreement was very good (kappa = 0.83), and a consensus was reached in all cases. In 419 eyes (92.3%) there was no split bundle. A split superior bundle was seen in 29 eyes (6.4%). A split inferior bundle was observed in five eyes (1.1%), and in one eye (0.2%) a split bundle was seen superiorly and inferiorly. When considering subjects, a split superior bundle (either in the right eye, or in the left eye, or in both eyes) occurred in 12.0% of normal subjects. The 'superior maximum' parameter was significantly lower in eyes with a split superior bundle than in eyes with a single superior bundle (67.2 microm vs. 89.9 microm; P<0.001). The same was observed for the 'symmetry' parameter (0.88 microm vs. 0.98 microm; P<0.001)., Conclusions: Split nerve fiber layer bundles are a common finding in healthy eyes when imaged with the GDx. A split superior bundle is the most frequent variation, in which cases an abnormal superior maximum or symmetry parameter, otherwise potential indicators of glaucoma, should not readily be interpreted as abnormal.

Purpose: To determine the reproducibility of measurements with the Nerve Fiber Analyzer, a scanning laser polarimeter designed for quantifying glaucoma in healthy patients and patients with glaucoma. The authors also assessed the variance of measurements between instruments., Methods: Measurements were made with the third generation Nerve Fiber Analyzer, the GDx. The study consisted of three parts. In the first part, the authors measured the right eyes of 10 healthy volunteers on 5 consecutive days. In the second part, 45 patients with glaucoma underwent Nerve Fiber Analyzer measurements of one randomly selected eye on two separate days in a 5-week period. For all 14 available parameters, reproducibility of measurements was expressed in terms of 95% limits of agreement and as the intraclass correlation coefficient. The Nerve Fiber Analyzer software has an option of creating a mean image from a selection of single images; for both parts of the study, the reproducibility of measurements was calculated for a "single image," and a "mean-of-three" image. In the third part of the study, 17 volunteers underwent repeated Nerve Fiber Analyzer measurement sessions on each of three different instruments. Using multivariate analysis of variance, the authors determined the variance of measurements between instruments., Results: The reproducibility of measurements varied considerably across parameters. Limits of agreement in mean images for superior maximum and inferior maximum were 7.2 microm and 7.7 microm, respectively in the healthy volunteers, and 8.7 microm and 7.9 microm, respectively in the patients with glaucoma. For healthy patients, the intraclass correlation coefficient was greater than 90% in 10 of 14 parameters. In patients with glaucoma, the intraclass correlation coefficient was greater than 90% in 13 of 14 parameters. Some parameters reproduced better in a mean than in a single image; these differences, however, were small and generally not statistically significant. The between-instruments component also varied across parameters and was highest in ratio-based parameters., Conclusions: The reproducibility of measurements varied across parameters. In general, the reproducibility of measurements with the Nerve Fiber Analyzer was high. The reproducibility of measurements was similar between healthy patients and patients with glaucoma. Any measured change in nerve fiber layer thickness would be statistically significant if it exceeded approximately 7 or 8 microm in the superior maximum or inferior maximum parameter in healthy patients. Reproducibility of measurements hardly differed between single images and mean images. The reproducibility of measurements among the three instruments we used was highest for straight parameters.

Background and Purpose: Amblyopia is characterized by histopathological changes in the visual cortex and lateral geniculate nucleus. In the retina, however, no abnormalities have yet been reported. The purpose of this study was to compare the nerve fiber layer (NFL) thickness in the amblyopic eye with that in the sound eye of patients with strabismic amblyopia. As a practical implication, we investigated the validity of comparing Nerve Fiber Analyzer (NFA) measurements obtained in amblyopic eyes to the normative database built into the NFA., Methods: NFL thickness was measured with a third generation NFA, the GDx (Laser Diagnostic Technologies, San Diego, CA). This is a scanning laser polarimeter, designed for monitoring glaucoma. The following NFL thickness parameters (all in microns) were compared: average thickness, superior maximum, inferior maximum, superior average, inferior average, nasal median and temporal median. Twenty patients with strabismic amblyopia were imaged with the NFA. Patients had no nystagmus, neurological disease or glaucoma. Nine patients had amblyopia in the right eye, and 11 patients in the left eye., Results: In general, the sound eyes yielded higher thickness measures than the amblyopic eyes. These differences, however, were small, averaging only 1.5%, p = 0.6, and therefore not "statistically significant" at the p&le 0.05 level., Conclusions: Using the standard of "Statistical Significance = p< or =0.05", when amblyopic eyes are measured with the NFA, the built-in normative database may serve as the reference data