Complex Congenital Heart Defects Research Articles

Prenatal Diagnosis of Congenital Heart Disease: The Crucial Role of Perinatal and Delivery Planning

Although most congenital heart defects (CHDs) are asymptomatic at birth, certain CHD lesions are at significant risk of severe hemodynamic instability and death if emergent cardiac interventions are not performed in a timely fashion. Therefore, accurate identification of at-risk fetuses and appropriate delivery resource planning according to the degree of anticipated hemodynamic instability is crucial. Fetal echocardiography has increased prenatal CHD detection in recent years due to advancements in ultrasound techniques and improved obstetrical cardiac screening protocols, enabling the prediction of newborns’ hemodynamic status. This assessment can guide multidisciplinary resource planning for postnatal care, including selection of delivery site, delivery room management, and transport to a cardiac center based on CHD risk severity. This review will discuss fetal cardiovascular physiology and the circulatory changes that occur at the time of and immediately following birth, outline fetal echocardiographic findings used to risk-stratify newborns with CHDs, and outline principles for neonatal resuscitation and initial transitional care in neonates with these complex CHD lesions.

Exploring Complexity: A Case Report of a Cystic Hygroma With Complex Congenital Heart Defects and Annular Pancreas in a One-Year-Old Child

Exploring Complexity: A Case Report of a Cystic Hygroma With Complex Congenital Heart Defects and Annular Pancreas in a One-Year-Old Child

Original Article--Clinical and Procedural Characteristics of Successful Transcatheter Device Closure of Ostium Secundum Atrial Septal Defect in Symptomatic Children Weighing

This retrospective study sought to determine the feasibility of transcatheter atrial septal defect device closure in patients less than 15 kg, as well as to assess complication rates and the reasons for unsuccessful device closure. In general, the risks associated with transcatheter atrial septal defect device closure are believed and reported to be relatively low, but the evidence stems from trials involving adults and older children. Current guidelines do not recommend atrial defect closure in device closure in children <15 kg, due to limited data available for feasibility and safety of device closure in this group of patients. Retrospective review of all patients who underwent elective transcatheter closure of ostium secundum atrial septal defect between September 2013 to February 2022. We excluded all children above 15 kg, as well as those with complex congenital heart defects. Major and minor complications were predefined and indications for referral were evaluated. We identified 81 patients meeting criteria with a median procedural age of 3 years (1 year-8 years), and median weight of 12 kg (4-15 kg). Successful device closure was achieved in 95.1% (77/81) and in 4.9% (4/81), the procedure was aborted. There was 1 major (1.2%) and 1 minor (1.2%) complication, total complication rate (2.4%). 100% of the referrals had right heart enlargement and exertional dyspnoea, 18.5% had recurrent lower respiratory tract infection and 9.9% had failure to thrive. Rate of resolution of residual shunt was 95.1%. at post-procedure day 1 and 98.8% at post-procedure 3 and 6 months respectively. Percutaneous atrial septal defect closure can be done effectively and safely in symptomatic children weighing less than 15 kg in experienced centres. However, deferral for closure until the historically established timeline of around 4-5 years of age should be strongly considered in asymptomatic children.

Transcatheter Resolution of a Failed Neoconfluence in Pulmonary Atresia With Discontinuous Pulmonary Arteries

We present a case of a full-term newborn with complex congenital heart defects, including single-ventricle physiology and discontinuous pulmonary arteries. Prompt surgical intervention was performed, which involved pulmonary neoconfluence with autologous pericardium graft and systemic-to-pulmonary shunt placement. However, postoperative complications required stenting to address pulmonary artery stenosis.

The use of high-resolution SNP arrays to detect congenital cardiac defects

Objective Copy number variations (CNVs) detected by high-resolution single nucleotide polymorphism microarrays (SNP arrays) have been associated with congenital heart defects (CHDs). The genetic mechanism underlying the development of CHDs remains unclear. Methods High-resolution SNP arrays were used to detect CNVs and traditional chromosomal analyses, respectively, were carried out on 60 and 249 fetuses from gestational 12–37 weeks old, having isolated or complex CHDs that were diagnosed using prenatal ultrasound. Results Twenty of the 60 fetuses (33.5%) had abnormalities, of which 23 CNVs (12 pathogenic, five probable pathogenic and six of undetermined significance) were detected by SNP arrays, and two distinct CNVs were present in three of these fetuses. In addition, in 39 patients with isolated congenital heart disease who had normal karyotypes, abnormal CNVs were present in 28.2% (11/39), and in patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. In patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. Conclusions In conclusion, genome-wide high-resolution SNP array can improve the diagnostic rate and uncover additional pathogenic CNVs. The submicroscopic deletions and duplications of Online Mendelian Inheritance in Man (OMIM) genes found in this study have haploinsufficient (deletion) or triplosensitive (duplication) traits, which further clarify the etiology and inheritance of CHDs.

To the 85th anniversary of Vladimir P. Podzolkov

Vladimir P. Podzolkov celebrated his anniversary on November 15. He is an outstanding Russian scientist, cardiac surgeon, one of the founders of pediatric cardiac surgery. His name is associated with the formation and development of surgical treatment of complex congenital heart defects, including abnormalities of the intrathoracic location, which were previously considered inoperable. His fundamental works have formed modern pediatric cardiac surgery, his monographs and textbooks are reference books for the younger generation of cardiac surgeons and recognized professionals.

Fetal cardiac magnetic resonance imaging of the descending aorta in suspected left-sided cardiac obstructions.

Severe left-sided cardiac obstructions are associated with high morbidity and mortality if not detected in time. The correct prenatal diagnosis of coarctation of the aorta (CoA) is difficult. Fetal cardiac magnetic resonance imaging (CMR) may improve the prenatal diagnosis of complex congenital heart defects. Flow measurements in the ascending aorta could aid in predicting postnatal CoA, but its accurate visualization is challenging. To compare the flow in the descending aorta (DAo) and umbilical vein (UV) in fetuses with suspected left-sided cardiac obstructions with and without the need for postnatal intervention and healthy controls by fetal phase-contrast CMR flow. A second objective was to determine if adding fetal CMR to echocardiography (echo) improves the fetal CoA diagnosis. Prospective fetal CMR phase-contrast flow in the DAo and UV and echo studies were conducted between 2017 and 2022. A total of 46 fetuses with suspected left-sided cardiac obstructions [11 hypoplastic left heart syndrome (HLHS), five critical aortic stenosis (cAS), and 30 CoA] and five controls were included. Neonatal interventions for left-sided cardiac obstructions (n = 23) or comfort care (n = 1 with HLHS) were pursued in all 16 fetuses with suspected HLHS or cAS and in eight (27%) fetuses with true CoA. DAo or UV flow was not different in fetuses with and without need of intervention. However, DAo and UV flows were lower in fetuses with either retrograde isthmic systolic flow [DAo flow 253 (72) vs. 261 (97) ml/kg/min, p = 0.035; UV flow 113 (75) vs. 161 (81) ml/kg/min, p = 0.04] or with suspected CoA and restrictive atrial septum [DAo flow 200 (71) vs. 268 (94) ml/kg/min, p = 0.04; UV flow 89 vs. 159 (76) ml/kg/min, p = 0.04] as well as in those without these changes. Adding fetal CMR to fetal echo predictors for postnatal CoA did not improve the diagnosis of CoA. Fetal CMR-derived DAo and UV flow measurements do not improve the prenatal diagnosis of left-sided cardiac obstructions, but they could be important in identifying fetuses with a more severe decrease in blood flow across the left side of the heart. The physiological explanation may be a markedly decreased left ventricular cardiac output with subsequent retrograde systolic isthmic flow and decreased total DAo flow.

An in vitro characterization of a PCL-fibrin scaffold for myocardial repair

Each year in the United States approximately 10,000 babies are born with a complex congenital heart defect (CHD) requiring surgery in the first year of after birth. Several of these operations require the implantation of a full-thickness heart patch; however, the current patch materials available to pediatric heart surgeons are exclusively non-living and non-degradable, which do not grow with the patient and are prone to fail due to an inability to integrate with the heart. In this work, the goal was to develop a full-thickness, tissue engineered myocardial patch (TEMP) that is made from biodegradable components, strong enough to withstand the mechanical forces of the heart wall, and able to integrate with the heart and drive neotissue formation. Here, a thick and porous electrospun PCL scaffold filled with high-salt PEGylated fibrin was developed. The scaffold was found to be mechanically sufficient for heart wall repair. Vascular cells were able to infiltrate more than halfway through the scaffold in static culture within three weeks. The scaffold maintained pluripotent stem cells for at least four days, supports viable iPSC-derived cardiomyocytes, and fostered tissue thickening in vitro. The TEMP developed here and tested in vitro is promising for the repair of structural CHD and will next be assessed in situ.

Implantation of HeartMate III ventricular assist devices in children after surgical treatment of complex congenital heart defect: first experience

Background. There is quite a high number of patients with advanced heart failure (HF) who have undergone surgical treatment for complex congenital heart defects. Implantation of mechanical circulatory support systems is the only treatment option for patients with refractory end-stage heart failure. Only a few centers have experience in implantation of ventricular assist devices (VAD) in children, which is a major challenge for modern pediatric cardiac surgery. Objective: to present our first experience of implantation of HeartMate III VADs in patients after surgical correction of complex congenital heart defects. Materials and methods. From 2021 to 2022, at Bakulev Center for Cardiovascular Surgery, four HeartMate III systems were implanted in children with advanced HF, who had previously undergone surgery for a complex congenital heart defect. In one case, aortic valve implantation was carried out simultaneously with VAD implantation. Results. All patients were discharged from the center. One patient developed right-sided heart failure intraoperatively, which required the use of a right ventricular assist device (RVAD) for 8 days. There were no complications from the central nervous system, bleeding, pump thrombosis, or infection. Conclusion. HeartMate III can be implanted in patients with body weight ≥21 kg and BSA ≥0.88 m2 . Children’s tolerance to physical activity increases, they are fully adapted socially, and can attend school.

20-Year follow-up and comparison of valved conduits used for right ventricular outflow tract reconstruction: single-centre, propensity score match analysis.

Surgical repair of complex congenital heart defects with hypoplasia or atresia of the right ventricular outflow tract (RVOT) may require pulmonary valve implantation or replacement during the primary repair or reoperation. The purpose of this study is to evaluate the outcomes of cryopreserved homografts, bovine jugular vein conduits and decellularized Matrix P Plus N conduits in patients undergoing RVOT reconstruction at a single centre. Retrospective, single-centre review of 173 patients with 199 conduits undergoing right ventricle-to-pulmonary artery reconstruction with valved conduit from 2002 to 2022. A total of 199 conduits were implanted in 173 patients (62.8% male), with a mean age of 8.97 ± 8.5 years. The following 3 types of conduits were used: homografts 129 (64.8%), bovine jugular vein conduits 45 (22.7%) and Matrix P Plus N 25 (12.5%). During the mean follow-up duration of 8.6 ± 5.8 years, there were 20 deaths, 35 conduit reoperations and 44 catheter reinterventions. Overall survival, reoperation-free and catheter reintervention-free survival at 20 years were 83%, 67.8% and 65.6%, respectively. Multivariable Cox analysis identified younger patient age, smaller conduit size, low patient weight and primary diagnosis of common arterial trunk as risk factors for reoperation and catheter reintervention. Long-term outcomes of reconstruction of the RVOT using homografts, bovine jugular vein and Matrix P Plus N conduits were acceptable. The reoperation rate for conduit dysfunction did not differ significantly among groups. Over time, the need for conduit replacement was higher in smaller conduits and in patients with common arterial trunk diagnosis.

Functions of cilia in cardiac development and disease.

Errors in embryonic cardiac development are a leading cause of congenital heart defects (CHDs), including morphological abnormalities of the heart that are often detected after birth. In the past few decades, an emerging role for cilia in the pathogenesis of CHD has been identified, but this topic still largely remains an unexplored area. Mouse forward genetic screens and whole exome sequencing analysis of CHD patients have identified enrichment for de novo mutations in ciliary genes or non-ciliary genes, which regulate cilia-related pathways, linking cilia function to aberrant cardiac development. Key events in cardiac morphogenesis, including left-right asymmetric development of the heart, are dependent upon cilia function. Cilia dysfunction during left-right axis formation contributes to CHD as evidenced by the substantial proportion of heterotaxy patients displaying complex CHD. Cilia-transduced signaling also regulates later events during heart development such as cardiac valve formation, outflow tract septation, ventricle development, and atrioventricular septa formation. In this review, we summarize the role of motile and non-motile (primary cilia) in cardiac asymmetry establishment and later events during heart development.

Long-term outcome after surgical correction of sinus venosus defect in a nationwide register-based cohort study

ObjectivesLong-term results after sinus venosus defect (SVD) closure are sparse and many studies lack a proper control cohort. This nationwide cohort evaluated the long-term outcome after SVD surgery. MethodsThe study enrolled every surgical SVD correction from the nationwide hospital discharge registry (FHDR) and surgical registries of two tertiary centers. Patients with more complex congenital heart defects were excluded. Surgeries were performed from 1969 to 2019. Five sex and birth-year-matched controls per SVD patient were gathered from the general population. ResultsIn total, 182 surgical SVD corrections were performed during the study period. The median age at the time of surgery was 8.3 years (range 0.06–75.7), and the majority (77.5%, n = 141) were under 18 years old. The median follow-up period was 18 years (range 0.1–53).There was no significant difference in mortality during the follow-up (logrank p = 0.62, MRR 0.78, 95% CI: 0.30–2.0). However, SVD patients had elevated risk for new-onset atrial fibrillation (RR 4.9, 95% CI: 2.2–10.9), heart failure (RR 4.0, 95% CI: 1.2–13.2), ischemic heart disease (4.3, 95% CI, 1.5–11.7), migraine (RR 3.6, 95% CI: 1.5–9.1) and sick sinus syndrome, II- or III-degree AV-block or pacemaker implantation (RR 11.3, 95% CI: 2.9–43.8). ConclusionYoung patients with SVD have an excellent survival prognosis after the surgery. Risk for sick sinus syndrome or conduction disorders, atrial fibrillation, and heart failure remains elevated in the long-term follow-up.

A Tale of Intricate Connections: An Interesting Case of Congenital Heart Disease with Supraventricular Tachycardia

Double inlet left ventricle (DILV) is a rare complex congenital heart defect characterized by the presence of two atrioventricular valve orifices leading into a single left ventricle. Patients rarely survive beyond teenage years without surgical correction. Supraventricular tachycardia (SVT) in DILV is a rare occurrence that adds an additional layer of complexity to diagnosis and management. Here, we report an exceptional case of DILV who survived well into her fourth decade of life without any surgical correction. The patient presented to us with SVT which lead to the discovery of her unique cardiac anomaly.

Health and disability in Argentine children with complex congenital heart disease undergoing surgery. Outcomes at 2 years of life.

Introduction. Complex congenital heart defects are the most frequent malformations and entail a significant burden of disease. The objective of this study was to determine the health status and disability of children who underwent surgery at a tertiary care hospital. Population and methods. A total of 84 patients aged 21 to 39 months who had a surgery with extracorporeal circulation during their first year of life were assessed in terms of growth, neurodevelopment, and disability. Results. In most children, growth was below the 50 th percentile in all 3 parameters, and greater involvement was observed in those with an associated genetic disorder. The frequency of disability was 55%. In the group with isolated congenital heart disease, the severity of disease and a pathological neurological examination at discharge were associated with disability (p = 0.047 and p = 0.03). Having only public health coverage was associated with less access to timely interventions (p = 0.02). Conclusions. Nearly half of the patients develop moderate-severe disability. Being aware of morbidities beyond the cardiovascular aspect and risk factors is part of the health care team's scope. Barriers in access to appropriate interventions caution health care providers of the relevance of seeking strategies to overcome them and achieve the maximum development potential of patients.

Long-term neurodevelopmental outcome and serial cerebral magnetic resonance imaging assessment in Fontan patients at school age.

Children with univentricular congenital heart disease undergoing staged surgical palliation are at risk for impaired neurodevelopmental (ND) outcome. Little is known about the long-term effects on brain growth until school age. In a prospective two-centre study, consecutive patients undergoing stage I (Hybrid or Norwood) to stage III (Fontan procedure) were evaluated by 2 serial cerebral magnetic resonance imaging examinations, somatic growth and ND testing before Fontan procedure at 2 years of age (Bayley-III) and after Fontan at 6-8 years of age (Wechsler Intelligence Scale for Children-third edition). Magnetic resonance imaging findings were compared with 8 healthy controls. Medical and sociodemographic characteristics were documented and related to cerebral and ND findings. We examined 33 children (16 female) at a mean age of 2.3 (0.35) and 6.8 (± 0.7) years. The mean Bayley-III cognitive scales were 99.1 (9.9), language scales 98.4 (11.9) and motor scales 98.5 (13.8) at the first examination. Follow-up at school age showed a mean total IQ of 86.7 (13.6). The rate of structural brain lesions increased from 39% at 2 years to 58% at school age. Bayley-III language scale (P = 0.021) and mean Wechsler Intelligence Scale for Children-third edition (P = 0.019) were lower in children with pathological MR findings. Total brain volume (P < 0.001), total grey matter volume (P = 0.002), deep grey matter volume (P = 0.001) and white matter volume (P < 0.001) were smaller in patients compared to age- and gender-matched healthy controls. Smaller brain volumes and structural brain lesions in complex congenital heart defect patients at school age are associated with impaired ND outcome. For the evaluation of predictive surgical or clinical factors, larger multicentre studies are needed.

Parents' Psychological and Decision-Making Outcomes following Prenatal Diagnosis with Complex Congenital Heart Defect: An Exploratory Study.

Background. Parents with a fetus diagnosed with a complex congenital heart defect (CHD) are at high risk of negative psychological outcomes. Purpose. To explore whether parents' psychological and decision-making outcomes differed based on their treatment decision and fetus/neonate survival status. Methods. We prospectively enrolled parents with a fetus diagnosed with a complex, life-threatening CHD from September 2018 to December 2020. We tested whether parents' psychological and decision-making outcomes 3 months posttreatment differed by treatment choice and survival status. Results. Our sample included 23 parents (average Age[years]: 27 ± 4, range = 21-37). Most were women (n = 18), non-Hispanic White (n = 20), and married (n = 21). Most parents chose surgery (n = 16), with 11 children surviving to the time of the survey; remaining parents (n = 7) chose comfort-directed care. Parents who chose comfort-directed care reported higher distress ( = 1.51, s = 0.75 v.  = 0.74, s = 0.55; Mdifference = 0.77, 95% confidence interval [CI], 0.05-1.48) and perinatal grief ( = 91.86, s = 22.96 v.  = 63.38, s = 20.15; Mdifference = 27.18, 95% CI, 6.20-48.16) than parents who chose surgery, regardless of survival status. Parents who chose comfort-directed care reported higher depression ( = 1.64, s = 0.95 v.  = 0.65, s = 0.49; Mdifference = 0.99, 95% CI, 0.10-1.88) than parents whose child survived following surgery. Parents choosing comfort-directed care reported higher regret ( = 26.43, s = 8.02 v.  = 5.00, s = 7.07; Mdifference = 21.43, 95% CI, 11.59-31.27) and decisional conflict ( = 20.98, s = 10.00 v.  = 3.44, s = 4.74; Mdifference = 17.54, 95% CI; 7.75-27.34) than parents whose child had not survived following surgery. Parents whose child survived following surgery reported lower grief (Mdifference = -19.71; 95% CI, -39.41 to -0.01) than parents whose child had not. Conclusions. The results highlight the potential for interventions and care tailored to parents' treatment decisions and outcomes to support parental coping and well-being. Question: Do the psychological and decision-making outcomes of parents differ based on their treatment decision and survival outcome following prenatal diagnosis with complex CHD?Findings: In this exploratory study, parents who decided to pursue comfort-directed care after a prenatal diagnosis reported higher levels of psychological distress and grief as well as higher decisional conflict and regret than parents who decided to pursue surgery.Meaning: The findings from this exploratory study highlight potential differences in parents' psychological and decision-making outcomes following a diagnosis of complex CHD for their fetus, which appear to relate to the treatment approach and the treatment outcome and may require tailoring of psychological and decision support.

P49: Are We Timely Detecting Congenital Heart Defects in Bogotá and Cali (Colombia)?

Background: Congenital heart defects (CHD) are the main cause of infant mortality. Properly attending CHD demands strategies to improve prenatal diagnosis, planning birth on adequate hospitals, assure timely clinical care for complex cases, and guarantee follow-up and health care access for patients lifelong. Accordingly, Colombian normativity dictates that all pregnant women must have at least a first and second trimester screening with fetal heart examination, 7 to 10 prenatal control visits, and psychological support and information on voluntary termination. The aim of this study was to characterize demographics and prenatal care of expectant mothers of pediatric patients with a confirmed CHD diagnosis. Methods: This study was prospective and observational with an incidental sampling of 134 CHD patients treated at Fundación Cardioinfantil (Bogotá), Hospital Universitario San Ignacio (Bogotá), and Clinica Imbanaco (Cali) in Colombia. Women, after consent, were interviewed about demographics, prenatal care, pre and postnatal diagnosis, and children clinical evolution. We analyzed CHD according to their complexity (simple, moderate or complex) and clinical presentation (isolated, multiple anomalies or syndromes). Data were collected using the REDCap tool, descriptive statistics were calculated using Excel. Variables were expressed as mean (range). Results: 43% of all CDH were prenatally detected (66% of complex CHD were only detected postnatally). Mothers were young (mean age 28.1 years, DE 6.2), 82.1% had completed high school, 71.6% had low-income and 82.1% lived in urban areas with the father. Only 3% had twin pregnancies and 19% had chronic comorbidities (hypertensive disorders, diabetes, or hypothyroidism). On average, mothers had 6.8 prenatal control visits (DE 2.6) and 4.6 ultrasound scans (DE 2.5). As for the proper moment for ultrasound scans, only 61.1% of first-trimester scans and 58.9% of second-trimester scans were on time according to normative. 41% of women did not have psychological support, and 49% did not receive information on voluntary termination. About labor, 45% were spontaneous and 55% cesarian deliveries. Regarding babies (50.7% females), 24.0% were small for gestational age and 25.4% were born before 37 weeks. Most babies had an isolated CHD (15% simple, 76% complex), 5% had multiple anomalies, and 5% syndromes. Comparing prenatal diagnosis (ultrasound scans) and postnatal diagnosis, only in 22% of cases we found a complete agreement, and in 56% CDH was not reported on the ultrasound exams. Conclusion: Ultrasonography is a useful tool to detect CHD, but improving early detection requires better and timely access, especially for complex cases. Colombian normative for prenatal care is not working as expected. Delfos program is funded by Minciencias (Contract No.120484267276).

Nationwide Survey Reveals High Prevalence of Non-Swimmers among Children with Congenital Heart Defects.

Physical activity is important for children with congenital heart defects (CHD), not only for somatic health, but also for neurologic, emotional, and psychosocial development. Swimming is a popular endurance sport which is in general suitable for most children with CHD. Since we have previously shown that children with CHD are less frequently physically active than their healthy peers, we hypothesized that the prevalence of non-swimmers is higher in CHD patients than in healthy children. To obtain representative data, we performed a nationwide survey in collaboration with the German National Register of Congenital Heart Defects (NRCHD) and the Institute for Sport Sciences of the Karlsruhe Institute for Technology (KIT). The questionnaire included questions capturing the prevalence of swimming skills and the timing of swim learning and was part of the "Motorik-Modul" (MoMo) from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). A representative age-matched subset of 4569 participants of the MoMo wave two study served as a healthy control group. From 894 CHD-patients (mean age of 12.5 ± 3.1 years), the proportion of non-swimmers in children with CHD was significantly higher (16% versus 4.3%; p < 0.001) compared to healthy children and was dependent on CHD severity: Children with complex CHD had an almost five-fold increased risk (20.4%) of being unable to swim, whereas in children with simple CHD, the ability to swim did not differ significantly from their healthy reference group (5.6% vs. 4.3% non-swimmers (p = not significant). According to our results, one in five patients with complex CHD are non-swimmers, a situation that is concerning in regard of motoric development, inclusion and integration, as well as prevention of drowning accidents. Implementation of swim learning interventions for children with CHD would be a reasonable approach.

Factors that Influence Placement of Gastrostomy Tube in Infants with Complex Congenital Heart Disease: A Single Center Study.

Factors that determine the need for Gastrostomy tube (G-tube) placement in infants with complex congenital heart defects (CHD) are variable. We aim to identify factors that improve counseling of expectant parents regarding postnatal outcomes and management. We performed a retrospective review of medical record of infants with prenatal diagnoses of complex CHD between 2015-2019 in a single tertiary care center and assessed risk factors for G-tube placement with linear regression. Of the 105 eligible infants with complex CHD, 44 infants required G-tube (42%). No significant association was observed between G-tube placement and chromosomal abnormalities, cardiopulmonary bypass time or type of CHD. Median days on noninvasive ventilation (4 [IQR 2-12] vs. 3 [IQR 1-8], p = 0.035), time at which gavage-tube feeds were started postoperatively (3 [IQR 2-8] vs. 2 [IQR 0-4], p = 0.0013), time to reach full-volume gavage-tube feeds (6 [IQR 3-14] vs. 5 [IQR 0-8], p = 0.038) and intensive care unit (ICU) length of stay (LOS) (41 [IQR: 21 - 90] vs. 18 [IQR: 7 - 23], p < 0.01) were associated with G-tube placement. Infants with ICU LOS duration longer than median had almost 7 times the odds of requiring a G-tube (OR: 7.23, 95% CI: 2.71-19.32; by regression). Delay in initiation and in reaching full-volume gavage-tube feeds after cardiac surgery, increased number of days spent on non-invasive ventilation and in the ICU were found to be significant predictors for G-tube placement. The type of CHD and the need for cardiac surgery were not significant predictors for G-tube placement.

Congenital heart defects caused by FOXJ1.

FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left-right organizer. Ablation or targeted mutation of Foxj1 in mice, zebrafish and frogs results in loss of ciliary motility and/or reduced length and number of motile cilia, affecting the establishment of the left-right axis. In humans, heterozygous pathogenic variants in FOXJ1 cause ciliopathy leading to situs inversus, obstructive hydrocephalus and chronic airway disease. Here, we report a novel truncating FOXJ1 variant (c.784_799dup; p.Glu267Glyfs*12) identified by clinical exome sequencing from a patient with isolated congenital heart defects (CHD) which included atrial and ventricular septal defects, double outlet right ventricle (DORV) and transposition of the great arteries. Functional experiments show that FOXJ1 c.784_799dup; p.Glu267Glyfs*12, unlike FOXJ1, fails to induce ectopic cilia in frog epidermis in vivo or to activate the ADGB promoter, a downstream target of FOXJ1 in cilia, in transactivation assays in vitro. Variant analysis of patients with heterotaxy or heterotaxy-related CHD indicates that pathogenic variants in FOXJ1 are an infrequent cause of heterotaxy. Finally, we characterize embryonic-stage CHD in Foxj1 loss-of-function mice, demonstrating randomized heart looping. Abnormal heart looping includes reversed looping (dextrocardia), ventral looping and no looping/single ventricle hearts. Complex CHDs revealed by histological analysis include atrioventricular septal defects, DORV, single ventricle defects as well as abnormal position of the great arteries. These results indicate that pathogenic variants in FOXJ1 can cause isolated CHD.