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Cervical aortic arch (CAA) and retro-aortic innominate vein (RAIV) are rare entities which can be associated with one another in a structurally normal heart. Less well recognized is the fact, that a third entity may often be present as well, since aortic arch abnormalities are common in a CAA. Hence, these three entities (CAA, RAIV, and an arch anomaly - in this case a post-ductal coarctation) may present as a triad. We present the first prenatal diagnosis of this rare triad which can be explained by common embryological origins which are discussed along with instructive aspects in diagnosis and management.

Background In repaired tetralogy of Fallot (rTOF), abnormal left ventricular (LV) rotational mechanics are associated with adverse clinical outcomes. We performed a comprehensive analysis of LV rotational mechanics in rTOF patients using cardiac magnetic resonance (CMR) prior to and following surgical pulmonary valve replacement (PVR). Methods In this single center retrospective study, we identified rTOF patients who (1) had both a CMR ≤ 1 year before PVR and ≤ 5 years after PVR, (2) had no other intervening procedure between CMRs, (3) had a body surface area > 1.0 m2 at CMR, and (4) had images suitable for feature tracking analysis. These subjects were matched to healthy age- and sex-matched control subjects. CMR feature tracking analysis was performed on a ventricular short-axis stack of balanced steady-state free precession images. Measurements included LV basal and apical rotation, twist, torsion, peak systolic rates of rotation and torsion, and timing of events. Associations with LV torsion were assessed. Results A total of 60 rTOF patients (23.6 ± 7.9 years, 52% male) and 30 healthy control subjects (20.8 ± 3.1 years, 50% male) were included. Compared with healthy controls, rTOF patients had lower apical and basal rotation, twist, torsion, and systolic rotation rates, and these parameters peaked earlier in systole. The only parameters that were correlated with LV torsion were right ventricular (RV) end-systolic volume (r = − 0.28, p = 0.029) and RV ejection fraction (r = 0.26, p = 0.044). At a median of 1.0 year (IQR 0.5–1.7) following PVR, there was no significant change in LV rotational parameters versus pre-PVR despite reductions in RV volumes, RV mass, pulmonary regurgitation, and RV outflow tract obstruction. Conclusion In this comprehensive study of CMR-derived LV rotational mechanics in rTOF patients, rotation, twist, and torsion were diminished compared to controls and did not improve at a median of 1 year after PVR despite favorable RV remodeling.

Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe life-threatening manifestation of SARS-CoV-2 infection. Acute cardiac dysfunction and resultant cardiogenic shock are common in children with MIS-C. While most children recover rapidly from acute illness, the long-term impact on the myocardium and cardiac function is unknown. Methods In this prospective study, cardiac MRI (CMR) was performed on patients 10 years old. Native T1 and T2 mapping values were compared with 20 children with normal CMR examinations. Results We performed CMRs on 13 subjects at a median age of 13.6 years (interquartile range [IQR] 11.9-16.0) and a median time from hospitalization of 8.2 months (IQR 6.8-9.6). Twelve subjects displayed normal ventricular function with a median left ventricle ejection fraction (LVEF) of 57.2% (IQR 56.1-58.4) and median right ventricular (RV) EF of 53.1% (IQR 52.0-55.7). One subject had low normal EF (52%). There was normal T2 and native T1 as compared to normal controls. There was qualitatively no evidence of edema by T2 weighted imaging. One subject had late gadolinium enhancement (LGE) at the inferior insertion point and mid-ventricular inferolateral region, with normal EF, no evidence of edema or perfusion defects, and normal T1 and T2 times. When stratifying by a history of abnormal LVEF (LVEF

Strain values vary with age in children and are both vendor- and platform-specific. Philips QLab 10.8 and Tomtec AutoStrain are two widely-utilized strain analysis platforms, and both incorporate recent EACVI-ASE-Industry Strain Standardization Task Force guidelines. We sought to establish normal strain values and Z-scores for both platforms using a large dataset of healthy children and to compare values among these two platforms and a previous version-QLab 10.5-which predated the Task Force guidelines.Echocardiograms from 1,032 subjects21 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 were 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 by QLab 10.5. Strain values were compared among the three platforms.For both of the newer platforms, strain varied with age, with magnitude reaching a maximum at 4-5 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 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.We generated normal RV and LV strain values and Z-scores from a large cohort of children for two commonly-utilized platforms in pediatric echocardiography laboratories. Following 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 inter-platform measurements.

Introduction: Congenitally corrected transposition of the great arteries (ccTGA) is rare with varied associated cardiac defects and rhythm abnormalities. We aimed to describe the natural history, associated anomalies and prenatal outcome in a cohort of prenatally diagnosed patients in which biventricular repair is anticipated. Methods: A retrospective cohort study was conducted via the Fetal Heart Society Research Collaborative. All fetuses with ccTGA encountered at 15 North American cardiac centers between 1/2004-7/2020 were identified. Fetuses with a hypoplastic ventricle precluding biventricular repair were excluded. Data is presented as median (interquartile range). Results: Inclusion criteria were met in 139 fetuses who were diagnosed with ccTGA at 24 (21-29) weeks. There was a family history of congenital heart disease in 12%. Maternal diabetes was present in 10%. Prenatal genetic testing in 50 pregnancies was normal. Excluding 14 fetuses with heterotaxy, extracardiac anomalies were observed in 9/125 (7.1%). Associated cardiac/extracardiac defects are detailed in table 1. Fetal atrioventricular block (AVB) was present in 17 fetuses (12%), diagnosed at a median of 26 (23-28), range 20-36 weeks. Two fetuses had SVT; 1 self-resolved and 1 during labor. Change occurred during follow-up in 34 fetuses, most commonly in severity of tricuspid regurgitation (6 improved, 4 worsened) and worsening of pulmonary stenosis (n=5). There were 112 live births, 17 terminations, 2 fetal deaths (FD) and 8 lost to follow-up. Both fetuses with FD had AVB, making the intrauterine mortality associated with fetal AVB 11.8% (2/17). Conclusions: This study represents the largest cohort to date of fetuses with ccTGA. Fetal ccTGA is associated with a spectrum of cardiac defects that may evolve, with extracardiac pathology occurring in 7.1%. AVB is found in 12% of fetuses and is a risk factor for FD. This data informs fetal counseling and can aid in delivery planning and perinatal care.

Pulmonary hypertension (PH) is a well-recognized complication of sickle cell disease (SCD) and is one of the strongest predictors of increased morbidity and mortality in adult patients. There is evidence that PH can develop in children with SCD and the clinical implications of this finding are an area of active research. We review the current literature examining the association of SCD and PH in childhood. The recent literature has focused on elucidating the multifactorial mechanisms for the development of PH in SCD with the goal of developing targeted therapies. In addition, there has been a focus on understanding the significance of echocardiographic evidence of PH in children with SCD, a finding that has recently been associated with adverse clinical factors. While still based on limited evidence, the increased understanding of the important prognostic implications of echocardiographic evidence of PH has led to the development of guidelines that recommend screening echocardiograms beginning in childhood in children with SCD. PH can develop in children with SCD and, while the exact clinical implications of this finding are still being elucidated, current guidelines and research are aimed at early identification and treatment to improve outcomes.

Purpose To develop and validate a new cardiac self-gating algorithm using blind source separation for 2D cine steady-state free precession (SSFP) imaging. Methods A standard cine SSFP sequence was modified so that the center point of k-space was sampled with each excitation. The center points of k-space were processed by 4 blind source separation methods, and used to detect heartbeats and assign k-space data to appropriate time points in the cardiac cycle. The proposed self-gating technique was prospectively validated in 8 patients against the standard electrocardiogram (ECG)-gating method by comparing the cardiac cycle lengths, image quality metrics, and ventricular volume measurements. Results There was close agreement between the cardiac cycle length using the ECG- and self-gating methods (bias 0.0 bpm, 95% limits of agreement ±2.1 bpm). The image quality metrics were not significantly different between the ECG- and self-gated images. The ventricular volumes, stroke volumes, and mass measured from self-gated images were all comparable with those from ECG-gated images (all biases Conclusion The self-gating method yielded comparable cardiac cycle length, image quality, and ventricular measurements compared with standard ECG-gated cine imaging. It may simplify patient preparation, be more robust when there is arrhythmia, and allow cardiac gating at higher field strengths.

Speckle tracking echocardiography (STE)-derived strain indices are believed to detect early cardiac dysfunction in survivors of childhood cancer and have potential to identify patients who may benefit from early heart failure treatment. However, effects of heart failure treatment on STE-derived strain measurements in this population are unknown. The aim of this study was to assess STE-derived strain measurements in survivors of childhood cancer treated with angiotensin converting enzyme inhibition or receptor blockade (ACEi/ARB). Two-dimensional speckle tracking analysis was retrospectively performed on echocardiograms from childhood cancer survivors before and during therapy with ACEi/ARB. Global left ventricular longitudinal and circumferential strain (GLS and GCS) and strain rates (LSR and CSR) were assessed and correlated with conventional echocardiographic measures of function. In 22 childhood cancer survivors (median age: 14.8, range 6.4–21.6 years), mean GLS (− 13.83 ± 0.74% to − 15.94 ± 0.74%, p = 0.002), GCS (− 18.79 ± 1.21% to − 20.74 ± 0.84%, p = 0.027), LSR (− 0.78 ± 0.04 to − 0.88 ± 0.04 s−1, p = 0.022), and CSR (− 1.08 ± 0.07 to − 1.21 ± 0.06 s−1, p = 0.027) improved on therapy. Improvement in GLS was maintained for greater than 1 year on ACEi/ARB (p = 0.02). Measures of strain and strain rate correlated with standard echocardiographic measures of function and were reproducible. These findings support the use of ACEi/ARB to treat post-chemotherapy-related cardiovascular changes in childhood cancer survivors, provide proof-of-concept that STE-derived strain and strain rate may be used to reliably monitor cardiac function during therapy, and support continued investigation into the clinical benefit of strain measurements in this population.

Transcatheter closure of mitral paravalvular leaks has become an accepted alternative to surgical repair, especially in patients at high risk for reoperation. Device placement using three-dimensional (3D) transesophageal echocardiography (TEE) guidance allows en-face views of the valve and provides detailed information for device sizing and placement. We present a case demonstrating hybrid transapical transcatheter 3D TEE-guided closure of two mitral paravalvular leaks. We demonstrate real time 3D TEE guidance for device sizing and placement, and early real time recognition of mechanical mitral valve leaflet impairment during device deployment.

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.

Cardiac abnormalities have been described in echocardiograms of children with sickle cell disease (SCD). However, longitudinal studies investigating progression of echocardiographic abnormalities across the pediatric age spectrum in SCD are lacking.A retrospective longitudinal analysis of 829 echocardiograms from pediatric patients with SCD at steady-state was performed. Left heart parameters included left ventricular end-systolic, end-diastolic diameters, fractional shortening, and mass. Right ventricular pressure was estimated by tricuspid regurgitation gradient. Tricuspid regurgitation gradient ≥25 mm Hg, a z-score ≥2 for LV parameters and ≤-2 for left ventricular fractional shortening were considered abnormal.Kaplan-Meier analysis revealed that echocardiographic abnormalities were detected by 5 years of age, and the cumulative incidence progressively increased throughout childhood. Age, male gender, HbSS and Sβ thalassemia genotype, white blood cell count, platelet count, total bilirubin, admissions for pain crises and acute chest syndrome were positively, whereas hemoglobin was negatively associated with cardiac abnormalities.Cardiac abnormalities began early in childhood and progressively increased with age. Our study highlights the high cumulative incidence of cardiac abnormalities in children with SCD, which could represent a marker of disease severity.

Heart rate variability (HRV) has become an important clinical marker of cardiovascular health and a research measure for the study of the cardiac conduction system and its autonomic controls. While the zebrafish ( Danio rerio) is an ideal vertebrate model for understanding heart development, HRV has only recently been investigated in this system. We have previously demonstrated that nkx2.5 and nkx2.7, two homologues of Nkx2–5 expressed in zebrafish cardiomyocytes, play vital roles in maintaining cardiac chamber-specific characteristics. Given observed defects in ventricular and atrial chamber identities in nkx2.5−/− embryos coupled with conduction system abnormalities in murine models of Nkx2.5 insufficiency, we postulated that reduced HRV would serve as a marker of poor cardiac health in nkx2.5 mutants and in other zebrafish models of human congenital heart disease. Using live video image acquisition, we derived beat-to-beat intervals to compare HRV in wild-type and nkx2.5−/− embryos. Our data illustrate that the nkx2.5 loss-of-function model exhibits increased heart rate and decreased HRV when compared with wild type during embryogenesis. These findings validate HRV analysis as a useful quantitative tool for assessment of cardiac health in zebrafish and underscore the importance of nkx2.5 in maintaining normal heart rate and HRV during early conduction system development.

If coronary artery sequelae are the only suggestive signs of previous Kawasaki disease, the diagnosis may easily be missed. We describe a rare case of a child with severe occlusive coronary disease likely owing to missed Kawasaki disease. This diagnosis was not initially considered given the age and absence of suggestive history. Careful echocardiographic assessment and low-radiation coronary CT angiogram resulted in successful diagnosis and treatment.

Objective This study aims to elicit physician and nursing perceptions about initiation of minimal enteral feedings (MEF) in very low-birth-weight (VLBW) infants. Study Design A three-phase, mixed methods study including a quantitative chart review of 37 VLBW infants, followed by 26 qualitative observations of morning rounds, 26 interviews of neonatal intensive care unit (NICU) medical team members, tailored interventions based on the identified barriers to MEF, and finally a postintervention chart audit of 50 VLBW infants. Results The main barriers to initiation of MEF were failure to appreciate the differences between the goals of MEF versus nutritive feedings, inconsistent definition of “sick” infant, indomethacin for intraventricular hemorrhage prophylaxis, awaiting mother's own milk, complicated feeding protocols/algorithms for feeding intolerance, and lack of buy-in from nurses/nurse practitioners. The compliance with early initiation of MEF per the feeding guidelines rose from 25 to 92% after our interventions. Conclusion Understanding the complex interplay of provider, system and patient-based factors that interfere with initiation of MEF may enable NICUs to develop consensus guidelines and targeted interventions and to achieve timely initiation of nonnutritive feedings.

The mitral–aortic intervalvular fibrosa is an area of fibrous continuity between the mitral and aortic valves. We present the first case of a congenital pseudoaneurysm in this region, detected prenatally as an isolated cardiac defect, which was followed-up conservatively postnatally. The diagnosis was confirmed by echocardiogram demonstrating blood flow into the pouch during systole and into the left ventricular outflow tract during diastole. The infant has been followed-up with serial echocardiograms demonstrating stable size and appearance of the lesion, without signs of obstruction, making close continued observation a reasonable approach.

Evolution of right ventricular (RV) systolic function after pediatric heart transplantation (HT) has not been well described.We analyzed echocardiograms performed over the first year after HT among children and young adults who remained rejection-free. Ninety-six patients (median age 7.1 [0.1-24.4] years at HT) were included: 22 infants (≤1 year) and 74 noninfants (1 year). Two-dimensional tricuspid annular plane systolic excursion (TAPSE), tissue Doppler-derived tricuspid annular systolic velocity (S'), fractional area change (FAC), myocardial performance index (MPI), and two-dimensional speckle-tracking-derived RV global longitudinal (GLS) and free wall strain (FWS) were assessed.All measures of RV function were impaired immediately after HT and significantly improved over the first year: TAPSE z-score (-8.15 ± 1.88 to -3.94 ± 1.65, P .0001), S' z-score (-4.30 ± 1.36 to -2.28 ± 1.33, P .0001), FAC (24.37% ± 7.71% to 42.02% ± 7.09%, P .0001), MPI (0.96 ± 0.47 to 0.41 ± 0.22, P .0001), GLS (-10.37% ± 3.86% to -21.05% ± 3.41%, P .0001), and FWS (-11.2% ± 4.08% to -23.66% ± 4.13%, P .0001). By 1 year post-HT, TAPSE, S', GLS, and FWS, remained abnormal, whereas FAC and MPI nearly normalized. Patients transplanted during infancy demonstrated better recovery of RV systolic function.Although RV systolic function improved over the first year after HT in children and young adults without rejection, measures that assess longitudinal contractility remained abnormal at 1 year post-HT. These findings contribute to our understanding of RV myocardial contractility after HT in children and young adults and improve our ability to assess function quantitatively in this population.

RV systolic function is important early after HT; however, it has not been critically assessed in children using quantitative measures. The aim of this study was to describe the most validated and commonly used quantitative echocardiographic measures of RV systolic function early after pediatric HT and to assess associations with qualitative function evaluation and clinical factors. RV systolic function was quantified on the first post-HT echocardiogram >24 hours after cardiopulmonary bypass using two-dimensional TAPSE, Tricuspid annular S', FAC, and MPI. In 145 patients (median age 7.6 years), quantitative RV systolic function was markedly abnormal: mean TAPSE z-score -8.43 ± 1.89; S' z-score -4.36 ± 1.22; FAC 24.4 ± 8.34%; and MPI 0.86 ± 0.51. Few patients had normal quantitative function: TAPSE (0%), S' (1.2%), FAC (9.4%), and MPI (28.4%). In contrast, 48.3% were observed as normal by qualitative assessment. Most clinical factors, including diagnosis, pulmonary vascular resistance, posttransplant hemodynamics, inotropic support, and rejection, were not associated with RV function. In this large pediatric HT population, TAPSE, S', FAC, and MPI were strikingly abnormal early post-HT despite reassuring qualitative assessment and no significant association with clinical factors. This suggests that the accepted normal values of these quantitative measures may not apply in the early post-HT period to accurately grade RV systolic function, and there may be utility in adapting a concept of normal reference values after pediatric HT.

Protein metabolism, consisting of both synthesis and degradation, is highly complex, playing an indispensable regulatory role throughout physiological and pathological processes. Over recent decades, extensive efforts, using approaches such as autoradiography, mass spectrometry, and fluorescence microscopy, have been devoted to the study of protein metabolism. However, noninvasive and global visualization of protein metabolism has proven to be highly challenging, especially in live systems. Recently, stimulated Raman scattering (SRS) microscopy coupled with metabolic labeling of deuterated amino acids (D-AAs) was demonstrated for use in imaging newly synthesized proteins in cultured cell lines. Herein, we significantly generalize this notion to develop a comprehensive labeling and imaging platform for live visualization of complex protein metabolism, including synthesis, degradation, and pulse–chase analysis of two temporally defined populations. First, the deuterium labeling efficiency was optimized, allowing time-lapse imaging of protein synthesis dynamics within individual live cells with high spatial–temporal resolution. Second, by tracking the methyl group (CH3) distribution attributed to pre-existing proteins, this platform also enables us to map protein degradation inside live cells. Third, using two subsets of structurally and spectroscopically distinct D-AAs, we achieved two-color pulse–chase imaging, as demonstrated by observing aggregate formation of mutant hungtingtin proteins. Finally, going beyond simple cell lines, we demonstrated the imaging ability of protein synthesis in brain tissues, zebrafish, and mice in vivo. Hence, the presented labeling and imaging platform would be a valuable tool to study complex protein metabolism with high sensitivity, resolution, and biocompatibility for a broad spectrum of systems ranging from cells to model animals and possibly to humans.

We developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and developed analogous mouse models to study mechanisms of neovessel formation. We previously reported that seeded human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As a consequence, the resulting neovessel was entirely of host cell origin. Here, we investigate the source of neotissue cells in syngeneic BMMC-seeded grafts, implanted into immunocompetent mouse recipients. We again find that seeded BMMCs are lost, declining to 0.02% at 14 d, concomitant with host macrophage invasion. In addition, we demonstrate using sex-mismatched chimeric hosts that bone marrow is not a significant source of endothelial or smooth muscle cells that comprise the neovessel. Furthermore, using composite grafts formed from seeded scaffold anastomosed to sex-mismatched natural vessel segments, we demonstrate that the adjacent vessel wall is the principal source of these endothelial and smooth muscle cells, forming 93% of proximal neotissue. These findings have important implications regarding fundamental mechanisms underlying neotissue formation; in this setting, the tissue-engineered construct functions by mobilizing the body's innate healing capabilities to “regenerate” neotissue from preexisting committed tissue cells.—Hibino, N., Villalona, G., Pietris, N., Duncan, D. R., Schoffner, A., Roh, J. D., Yi, T., Dobrucki, L. W., Mejias, D., Sawh-Martinez, R., Harrington, J. K., Sinusas, A., Krause, D. S., Kyriakides, T., Saltzman, W. M., Pober, J. S., Shin'oka, T., Breuer, C. K. Tissue-engineered vascular grafts form neovessels that arise from regeneration of the adjacent blood vessel.