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.

Histopathology of resected tissue from repair of anomalous aortic origin of a coronary artery: Potential mechanism of coronary artery compression.

Objective: This study aimed to describe the histomorphologic characteristics of resected (unroofed) common wall tissue from repair of anomalous aortic origin of a coronary artery and to determine whether the histologic features correlate with clinical and imaging findings. Methods: The histology of resected tissue was analyzed and reviewed for the presence of fibrointimal hyperplasia, smooth muscle disarray, mucoid extracellular matrix accumulation, mural fibrosis, and elastic fiber disorganization and fragmentation using hematoxylin and eosin and special stains. Clinical, computed tomography imaging, and surgical data were correlated with the histopathologic findings. Results: Twenty specimens from 20 patients (age range, 7-18 years; 14 males) were analyzed. Anomalous aortic origin of a coronary artery involved the right coronary in 16 (80%), and a slit-like ostium was noted in 18 (90%). By computed tomography imaging, the median proximal coronary artery eccentricity index was 0.4 (range, 0.20-0.90). The median length of intramural course was 8.2 mm (range, 2.6-15.2 mm). The anomalous vessel was determined to be interarterial in 14 patients (93%, 15 had evaluable images). The median distance from a commissure was 2.5 mm above the sinotubular junction (STJ) (range: 2 mm below the STJ-14 mm above the STJ). Prominent histopathologic findings included elastic fiber alterations, mural fibrosis, and smooth muscle disarray. The shared wall of the aorta and intramural coronary artery is more similar to the aorta histologically. Mural fibrosis and elastic fiber abnormalities tended to be more severe in patients >10 years of age at the time of surgery, but this did not reach statistical significance. The extent of vascular changes did not appear to have a clear relationship with the imaging features. Conclusions: The findings confirm the aortic wall-like quality of the intramural segment of the coronary artery and the presence of pathologic alterations in the wall microstructure.

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 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.

Computed tomography angiography (CTA) of anomalous aortic origin of a coronary artery (AAOCA): Which measurements are accurate and reliable?

BACKGROUND: The variation and accuracy of computed tomography angiography (CTA) features of anomalous aortic origin of a coronary artery (AAOCA) have not been completely characterized. We evaluated anomalous right (AAORCA) and left (AAOLCA) coronary arteries by CTA, with an emphasis on reproducibility, comparison with surgical measurements, and effect of nitroglycerin. METHODS: CTAs were interpreted for location of coronary origin & exit from the aorta, course, and dominance; minor & major diameters of the proximal & distal coronaries; shape of orifice; and intramural length. Relationships between vessel measurements, body surface area (BSA), and nitroglycerin use were evaluated. Comparisons between CTA and surgical measurements included intramural length, surgical probe size pre-intervention vs. CTA proximal AAOCA diameter, and surgical probe size post-intervention vs. CTA distal AAOCA diameter. RESULTS: Of 104 patients [81 (78%) AAORCA], all but 1 were intramural. Compared to AAOLCA, AAORCA patients were more likely to have a high origin (91% vs. 31%, p â€‹< â€‹0.01), and slit-like orifice (58% vs. 26%, p â€‹< â€‹0.01). When CTAs with nitroglycerin were compared to those without, no difference in proximal AAOCA dimensions was identified; however distal AAOCA and normal-origin coronary dimensions were larger in scans with nitroglycerin. Aside from slit-like orifice, reliability of coronary CTA measurements, including proximal AAOCA minor diameter and intramural length, was moderate to good between readers. In a subgroup of 54 patients, proximal AAOCA minor diameter and intramural length had good agreement and correlation with surgery. CONCLUSION: Proximal AAOCA dimensions and intramural length are reproducible variables. The lack of difference in proximal AAOCA dimensions with nitroglycerin may reflect abnormal vessel mechanics. Multicenter studies are an important next step in understanding the generalizability of our findings.

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.

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.

Normal Left Ventricular Systolic and Diastolic Strain Rate Values in Children Derived from Two-Dimensional Speckle-Tracking Echocardiography.

BACKGROUND: Strain rate (SR) parameters derived from two-dimensional speckle-tracking echocardiography have prognostic value in children with heart disease. Routine use is hindered by a lack of normative data. The aim of this study was to determine reference values and Z scores for left ventricular systolic and diastolic SR in a large cohort of healthy children. METHODS: Echocardiograms from 577 subjects ≤18 years of age (mean age, 9.6 ± 5.6 years; range, 1 day to 18.0 years; 46% female) with structurally and functionally normal hearts were retrospectively included. Left ventricular longitudinal and circumferential systolic and early and late diastolic SR were measured using two-dimensional speckle-tracking echocardiography from the apical four-chamber and short-axis mid-papillary views. Associations with age and body surface area were assessed using Spearman correlation and generalized additive modeling. The relationship between systolic SR and wall stress (afterload) was examined. Analyses were conducted with and without correction for heart rate. Multivariable linear regression modeling was used to identify independent factors associated with the SR parameters. Z score equations were derived from a selected best-fit parametric model. RESULTS: All SR parameters differed significantly by age group. The magnitude of all SR values decreased with increasing age and body surface area. Systolic SR magnitude was inversely related to wall stress in children ≤7 years of age but not did not vary significantly in the older age groups. All relationships were maintained after heart rate correction. SR measurements had very good or excellent agreement. CONCLUSION: Longitudinal and circumferential systolic and diastolic SR parameters are presented from a large cohort of healthy children using two-dimensional speckle-tracking echocardiography from the Philips platform. SR values differ significantly by age and body surface area. These results suggest that the myocardium becomes less sensitive to afterload with maturity. Z score equations based on age are presented, which should promote further clinical and research use.

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.

Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury.

OBJECTIVES: To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI). METHODS: A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization. Patients undergoing revascularization and subsequent MT were compared with those undergoing revascularization alone (Control). RESULTS: Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic inflammatory response and organ function measured 1 day before and 7 days following revascularization did not differ between groups. Successful separation from ECMO-defined as freedom from ECMO reinstitution within 1 week after initial separation-was possible for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P = .02). Median circumferential strain immediately following IRI but before therapy was not significantly different between groups. Immediately following separation from ECMO, ventricular strain was significantly better in the MT group (-23.0%; range, -20.0% to -28.8%) compared with the Control group (-16.8%; range, -13.0% to -18.4%) (P = .03). Median time to functional recovery after revascularization was significantly shorter in the MT group (2 days vs 9 days; P = .02). Cardiovascular events were lower in the MT group (20% vs 79%; P < .01). Cox regression analysis showed higher composite estimated risk of cardiovascular events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9; P = .04) CONCLUSIONS: In this pilot study, MT was associated with successful separation from ECMO and enhanced ventricular strain in patients requiring postcardiotomy ECMO for severe refractory cardiogenic shock after IRI.

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.

Normal Values for Left Ventricular Strain and Synchrony in Children Based on Speckle Tracking Echocardiography.

Strain and synchrony are associated with clinical outcomes in children with heart diseases. Robust normative data for these values, measured by 2-dimensional speckle tracking echocardiography (2DSTE), are limited. Therefore, we aimed to derive normal ranges and z-scores of 2DSTE strain and synchrony parameters in children. Subjects were <21 years old with structurally and functionally normal hearts. High frame-rate 2-dimensional echocardiographic images were retrospectively analyzed to measure longitudinal (LS) and circumferential (CS) strain and synchrony; views used were apical 4, 2, and 3-chamber (AP 4, 2, 3) and mid-papillary short-axis (SAX-M). Synchrony measures included standard deviation of time to peak strain, maximal wall delay, and cross-correlation mean segmental delay; these were calculated without and with heart rate (HR) correction (divided by √RR). Z-score equations were created for AP4 and SAX-M strain components. n = 312 subjects (40% female) were included (age 3 days to 20.5 years). Mean strain values (%) were: AP4 -24.4 ± 3.2, AP2 -24.2 ± 3.3, AP3 -24.6 ± 3.4, SAX-M -25.8 ± 3.4. Significant differences between ages were present for all strain components (AP4 p < 0.001; AP2 p = 0.003; AP3 p = 0.014; SAX-M p = 0.01). LS components decreased with increasing age and body surface area (p < 0.001 for all); CS did not. Longitudinal, but not circumferential, synchrony parameters decreased with age; however, these were nonsignificant after HR correction. In conclusion, normal pediatric 2DSTE strain and synchrony parameters and z-scores are reported to provide a foundation for incorporation into clinical practice. LS decline with age whereas CS does not. Age-related decreases in LS synchrony were mostly nonsignificant when corrected for HR.