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INTRODUCTION: Reducing cardiopulmonary bypass (CPB) induced inflammatory injury is a potentially important strategy for children undergoing multiple operations for single ventricle palliation. We sought to characterize the soluble receptor for advanced glycation end products (sRAGE), a protein involved in acute lung injury and inflammation, in pediatric patients with congenital heart disease and hypothesized that patients undergoing single ventricle palliation would have higher levels of sRAGE following bypass than those with biventricular physiologies. METHODS: This was a prospective, observational study of children undergoing CPB. Plasma samples were obtained before and after bypass. sRAGE levels were measured and compared between those with biventricular and single ventricle heart disease using descriptive statistics and multivariate analysis for risk factors for lung injury. RESULTS: sRAGE levels were measured in 40 patients: 19 with biventricular and 21 with single ventricle heart disease. Children undergoing single ventricle palliation had a higher factor and percent increase in sRAGE levels when compared to patients with biventricular circulations (4.6 vs. 2.4, p = 0.002) and (364% vs. 181%, p = 0.014). The factor increase in sRAGE inversely correlated with the patients preoperative oxygen saturation (Pearson correlation (r) = -0.43, p = 0.005) and was positively associated with red blood cell transfusion (coefficient = 0.011; 95% CI: 0.004, 0.017; p = 0.001). CONCLUSIONS: Children with single ventricle physiology have greater increase in sRAGE following CPB as compared to children undergoing biventricular repair. Larger studies delineating the role of sRAGE in children undergoing single ventricle palliation may be beneficial in understanding how to prevent complications in this high-risk population.

Trithorax-related H3K4 methyltransferases, KMT2C and KMT2D, are critical epigenetic modifiers. Haploinsufficiency of KMT2C was only recently recognized as a cause of neurodevelopmental disorder (NDD), so the clinical and molecular spectrums of the KMT2C-related NDD (now designated as Kleefstra syndrome 2) are largely unknown. We ascertained 98 individuals with rare KMT2C variants, including 75 with protein-truncating variants (PTVs). Notably, ∼15% of KMT2C PTVs were inherited. Although the most highly expressed KMT2C transcript consists of only the last four exons, pathogenic PTVs were found in almost all the exons of this large gene. KMT2C variant interpretation can be challenging due to segmental duplications and clonal hematopoesis-induced artifacts. Using samples from 27 affected individuals, divided into discovery and validation cohorts, we generated a moderate strength disorder-specific KMT2C DNA methylation (DNAm) signature and demonstrate its utility in classifying non-truncating variants. Based on 81 individuals with pathogenic/likely pathogenic variants, we demonstrate that the KMT2C-related NDD is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, hypotonia, seizures, short stature, and other comorbidities. The facial module of PhenoScore, applied to photographs of 34 affected individuals, reveals that the KMT2C-related facial gestalt is significantly different from the general NDD population. Finally, using PhenoScore and DNAm signatures, we demonstrate that the KMT2C-related NDD is clinically and epigenetically distinct from Kleefstra and Kabuki syndromes. Overall, we define the clinical features, molecular spectrum, and DNAm signature of the KMT2C-related NDD and demonstrate they are distinct from Kleefstra and Kabuki syndromes highlighting the need to rename this condition.

BACKGROUND AND OBJECTIVE: Congenital heart defects are known to be associated with increased odds of severe COVID-19. Congenital anomalies affecting other body systems may also be associated with poor outcomes. This study is an exhaustive assessment of congenital anomalies and odds of severe COVID-19 in pediatric patients. METHODS: Data were retrieved from the COVID-19 dataset of Cerner® Real-World Data for encounters from March 2020 to February 2022. Prior to matching, the data consisted of 664,523 patients less than 18 years old and 927,805 corresponding encounters with COVID-19 from 117 health systems across the United States. One-to-one propensity score matching was performed, and a cumulative link mixed-effects model with random intercepts for health system and patients was built to assess corresponding associations. RESULTS: All congenital anomalies were associated with worse COVID-19 outcomes, with the strongest association observed for cardiovascular anomalies (odds ratio [OR], 3.84; 95% CI, 3.63-4.06) and the weakest association observed for anomalies affecting the eye/ear/face/neck (OR, 1.16; 95% CI, 1.03-1.31). CONCLUSIONS AND RELEVANCE: Congenital anomalies are associated with greater odds of experiencing severe symptoms of COVID-19. In addition to congenital heart defects, all other birth defects may increase the odds for more severe COVID-19. IMPACT: All congenital anomalies are associated with increased odds of severe COVID-19. This study is the largest and among the first to investigate birth defects across all body systems. The multicenter large data and analysis demonstrate the increased odds of severe COVID19 in pediatric patients with congenital anomalies affecting any body system. These data demonstrate that all children with birth defects are at increased odds of more severe COVID-19, not only those with heart defects. This should be taken into consideration when optimizing prevention and intervention resources within a hospital.

His-bundle pacing has demonstrated feasibility in numerous adult studies to reverse and prevent pacing-induced cardiomyopathy, however, is met with higher capture thresholds with deployment sheaths designed for adults with his-bundles in the typical location. To describe 24 pediatric and adult congenital patients post-physiologic pacing. Patients at the University of Minnesota Masonic Childrens Hospital with congenital complete heart block or congenital heart disease and atrioventricular block presented for pacemaker placement between November 2019 and January 2021. Twenty-four patients had attempted his-bundle placement using either Medtronics C315 or C308 sheaths and 3830 leads except for 3 patients who had Boston Scientifics His system with the Shape 3 sheath and 7842 leads. Twenty-four total patients underwent physiologic pacing (23 his-bundle, 13 female, 11 male) with median age of 14 years (range 8-39 years) with median weight of 51 kg (range 21.2-81 kg) with five right-sided implants performed. Twelve patients had congenital heart disease including atrioventricular canal defects, tetralogy of Fallot, and ventricular septal defect repairs (nine patients with ventricular septal defect repairs). Twelve patients had selective His-bundle pacing (six with congenital heart disease). Median threshold to capture was 0.5 V at 0.4 ms (range 0.4 to 1.1 V at 0.4 ms), impedance 570 ohms (range 456-1140 ohms), and sensing median of 9.7 mV (range 1.5-13.8 mV if present). The median follow-up time was 610 days (range 240-760 days). No complications occurred peri-procedurally or during follow-up. His-bundle pacing is feasible in pediatric and congenital heart disease patients.

BackgroundOxygen saturation (Spo2) screening has not led to earlier detection of critical congenital heart disease (CCHD). Adding pulse oximetry features (ie, perfusion data and radiofemoral pulse delay) may improve CCHD detection, especially coarctation of the aorta (CoA). We developed and tested a machine learning (ML) pulse oximetry algorithm to enhance CCHD detection.Methods and resultsSix sites prospectively enrolled newborns with and without CCHD and recorded simultaneous pre- and postductal pulse oximetry. We focused on models at 1 versus 2 time points and with/without pulse delay for our ML algorithms. The sensitivity, specificity, and area under the receiver operating characteristic curve were compared between the Spo2-alone and ML algorithms. A total of 523 newborns were enrolled (no CHD, 317; CHD, 74; CCHD, 132, of whom 21 had isolated CoA). When applying the Spo2-alone algorithm to all patients, 26.2% of CCHD would be missed. We narrowed the sample to patients with both 2 time point measurements and pulse-delay data (no CHD, 65; CCHD, 14) to compare ML performance. Among these patients, sensitivity for CCHD detection increased with both the addition of pulse delay and a second time point. All ML models had 100% specificity. With a 2-time-points+pulse-delay model, CCHD sensitivity increased to 92.86% (P=0.25) compared with Spo2 alone (71.43%), and CoA increased to 66.67% (P=0.5) from 0. The area under the receiver operating characteristic curve for CCHD and CoA detection significantly improved (0.96 versus 0.83 for CCHD, 0.83 versus 0.48 for CoA; both P=0.03) using the 2-time-points+pulse-delay model compared with Spo2 alone.ConclusionsML pulse oximetry that combines oxygenation, perfusion data, and pulse delay at 2 time points may improve detection of CCHD and CoA within 48 hours after birth.RegistrationURL: https://www.clinicaltrials.gov/study/NCT04056104?term=NCT04056104&rank=1; Unique identifier: NCT04056104.

Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2, respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.

ObjectiveOur objective was to gauge adherence to nationally endorsed protocols in implementation of pulse oximetry (POx) screening for critical congenital heart disease (CCHD) in infants after mandate by all states and to assess associated characteristics.Study designBetween March and October 2019, an online questionnaire was administered to nurse supervisors who oversee personnel conducting POx screening. The questionnaire used eight questions regarding performance and interpretation of screening protocols to measure policy consistency, which is adherence to nationally endorsed protocols for POx screening developed by professional medical societies. Multilevel linear regression models evaluated associations between policy consistency and characteristics of hospitals and individuals, state of hospital location, early versus late mandate adopters, and state reporting requirements.ResultsResponses from 189 nurse supervisors spanning 38 states were analyzed. Only 17% received maximum points indicating full policy consistency, and 24% selected all four options for potential hypoxia that require a repeat screen. Notably, 33% did not recognize ≤90% SpO2 as an immediate failed screen and 31% responded that an infant with SpO2 of 89% in one extremity will be rescreened by nurses in an hour rather than receiving an immediate physician referral. Lower policy consistency was associated with lack of state reporting mandates (beta = -1.23 p = 0.01) and early adoption by states (beta = -1.01, p

Intraseptal-course, ectopic coronary anomalies are not well characterized as to anatomy, function, prognosis, and treatment. Recently, a revolutionary but unsupported new theory is claiming that most patients with a Left Anomalous Coronary Artery originating from the Opposite Sinus with anomalous Intra-Septal course (L-ACAOS-IS)—even small children—have significant stenoses and require open-heart surgery to prevent acute myocardial infarction and death. This surprising view has spurred ongoing discussions among adult and pediatric cardiologists and cardiac surgeons, compelling us (the conservative party in the discussion) to offer an in-depth and comprehensive review of this anomaly, based on objective but opposite data. We and other adult cardiologists have followed numerous L-ACAOS-IS patients for many years and have observed none of the claimed catastrophes. Rather, we have consistently found that L-ACAOS-IS generally has a benign clinical prognosis. We present the general principle of coronary artery dysfunction in anatomical congenital anomalies (that only significant luminal coronary stenosis can have clinical repercussions). We then review anatomical and functional details of L-ACAOS-IS related to prognosis and treatment indications, which could explain many of the clinical presentations recently mentioned. Finally, we encourage our more liberal colleagues to recognize that, compared with normal coronary arteries, those with anomalies of origin and course are associated with frequent coronary spasm. In particular, we underscore that some of the ischemic manifestations and other results might actually be caused by pressure wire–induced artifacts (rigid wires tend to cause coronary spasm when advanced into tortuous coronary arteries). [ABSTRACT FROM AUTHOR]

Background: Data on congenital heart diseases in neonates, especially critical congenital heart disease, varies worldwide. Developing countries have higher mortality than developed countries. To study the clinical profile of congenital heart diseases in neonates. Methods: Prospective observational study. Neonates admitted to a tertiary care hospital with congenital heart disease. Clinical details, investigations, and management of neonates admitted to a tertiary care hospital were studied prospectively. Results: Among the study neonates, 60% had acyanotic heart disease, the most common being ASD, while 40% had cyanotic heart disease, the most common being TGA—outborn cases comprised 60% of the total neonates. The most common presenting features were fast breathing and cyanosis; the most common clinical sign was murmur(59%). Among the study neonates, 15 cases had low calcium levels. Definitive surgery was done in 21 neonates, of which 7 succumbed. The staged repair was done in 9 neonates, of which 2 succumbed. Of 12 TGA cases,10 underwent definitive repair, and 7 did well at follow-up. Among the 10 TOF babies, 6 underwent staged repair. Out of the 7 cases of CoA, 6 underwent definitive surgery, and 1 expired. Among Critical CHD, mortality was 23.3%. Conclusion: The most common cyanotic heart disease was ASD, and the most common cyanotic heart disease was TGA. Surgery was done in 30 cases, out of which 9 succumbed, and mortality among surgical cases was 30%. At follow up TGA cases with definitive surgeries were doing well. Mortality was lower compared to other studies in India. Hypocalcemia was observed in 16.6% of the CHD cases, which needs to be studied in the future. [ABSTRACT FROM AUTHOR]

Background: The primary caregivers of children with congenital heart disease (CHD) after cardiac surgery at home are often their mothers. Therefore, the quality of life (QoL) and treatment adherence (TA) of mothers are crucial for the prognosis of these children. This study evaluated the impact of a mobile educational application on the QoL and TA in mothers of children with CHD undergoing cardiac surgery.Methods: This randomized clinical trial was conducted on 72 mothers of children with CHD referred for cardiac surgery to Children’s Medical Center Hospital, Tehran, Iran, from September 2023 to May 2024. Mothers were randomly assigned to intervention (n=36) and control (n=36) groups. The intervention group received the educational app upon discharge and used it for four weeks, while the control group received standard discharge education, which consisted of face-to-face education. Data were collected using a demographic form, the 36-Item Short Form Health Survey (SF-36), and the Modanloo Treatment Adherence Questionnaire at baseline and one month post-intervention. Data were analyzed using SPSS software version 26, with independent t-test, chi-square, and analysis of covariance. A significance level of P

Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow at well-resourced centers. Studies to evaluate the clinical value and cost-effectiveness of these techniques are needed. For techniques that enhance the value of care for congenital heart disease patients, resources will need to be allocated for education and training to promote widespread implementation.

Congenital Heart Disease (CHD) is one of the most common developmental anomalies seen in children and there is an increased risk of developing oral disease and its systemic effects in children with CHD. The present case report highlights the dental management of a 10-year-old boy with CHD and dextrocardia. The diagnosis for the patient included dextrocardia (where the position of the heart is developmentally changed from the left to the right-side), complete atrioventricular septal defect and double outlet right ventricle with pulmonary stenosis. After consultation, diagnosis and treatment planning and upon obtaining consent from the parents and modifying the child’s behaviour, the dental needs of the child were addressed on a visit-by-visit basis. A quadrant approach was adopted to complete the extractions of all retained carious primary teeth, followed by restorative treatment. Oral prophylaxis was performed, followed by topical fluoride application and the patient was then referred to the Department of Orthodontics for treatment of malalignment. This case report focuses on the guidelines followed for antibiotic prophylaxis against Infective Endocarditis (IE) and highlights the importance of maintaining good oral health for this group of patients. The dental management of children with CHD can be complex, as oral health is often neglected by both parents and patients. Cardiovascular problems can significantly impact both the child and the parent, affecting management and financial implications. The dental considerations require early diagnosis of dental problems and prompt treatment to prevent complications and difficulties in implementing treatment due to systemic repercussions. The present case report aimed to improve dental care for children with severe systemic alterations, as there is a lack of scientific literature regarding the dental management of paediatric patients with CHD.

The article discusses the anesthetic management of children with congenital heart disease (CHD) undergoing non-cardiac surgery, emphasizing the importance of understanding the physiological classification of CHD and long-term sequelae. Topics include the physiological approach to CHD classification, the long-term sequelae such as myocardial dysfunction and arrhythmias, and the risk stratification for non-cardiac surgery.

Congenital Heart Disease (CHD) is one of the most common developmental anomalies seen in children and there is an increased risk of developing oral disease and its systemic effects in children with CHD. The present case report highlights the dental management of a 10-year-old boy with CHD and dextrocardia. The diagnosis for the patient included dextrocardia (where the position of the heart is developmentally changed from the left to the right-side), complete atrioventricular septal defect and double outlet right ventricle with pulmonary stenosis. After consultation, diagnosis and treatment planning and upon obtaining consent from the parents and modifying the child's behaviour, the dental needs of the child were addressed on a visit-by-visit basis. A quadrant approach was adopted to complete the extractions of all retained carious primary teeth, followed by restorative treatment. Oral prophylaxis was performed, followed by topical fluoride application and the patient was then referred to the Department of Orthodontics for treatment of malalignment. This case report focuses on the guidelines followed for antibiotic prophylaxis against Infective Endocarditis (IE) and highlights the importance of maintaining good oral health for this group of patients. The dental management of children with CHD can be complex, as oral health is often neglected by both parents and patients. Cardiovascular problems can significantly impact both the child and the parent, affecting management and financial implications. The dental considerations require early diagnosis of dental problems and prompt treatment to prevent complications and difficulties in implementing treatment due to systemic repercussions. The present case report aimed to improve dental care for children with severe systemic alterations, as there is a lack of scientific literature regarding the dental management of paediatric patients with CHD. [ABSTRACT FROM AUTHOR]

Objectives. Necrotizing enterocolitis (NEC) is a main cause of neonatal morbimortality. Gut prematurity and ischemia-reperfusion injury contribute to NEC and characterize two different scenarios: prematurity and congenital cardiopathy (CC). Our aim is to investigate whether CC worsens NEC gastrointestinal and general prognosis. Materials and methods. NEC episodes from 2015-2023 were reviewed and classified into CC and non-CC. Patients with focal intestinal perforation were excluded. Data regarding NEC debut and management, surgical timing, intestinal segment involved and short-term outcomes were compared. Results. Out of 205 neonates, 15 were excluded for unavailable records or uncertain diagnosis. 190 cases were included, 59 with CC. Comparing CC and non-CC, no significant differences were found in weight or age at diagnosis, or NEC stage. Hemodynamic (HD) shock [38.98% vs 24.43% (p < 0.05)] and need for vasoactive support at debut were more frequent in CC patients [44.07% vs 23.66% (p < 0.05)]. No differences were found regarding need for surgery at debut, length of resected intestine or segment affected or days on parenteral nutrition. CC conditioned longer hospital stay [110.8 ± 68.4 days vs 68.4 ± 44.6 (p < 0.05)] and higher mortality [30.5 vs 11.5 (p < 0.05)]. Conclusions. NEC in CC patients presents more HD instability at debut and worse global prognosis, probably due to inherent cardiovascular compromise, but need for surgery, type of intestinal involvement and short-term outcomes are similar to non-CC NEC. [ABSTRACT FROM AUTHOR]

Background: Congenital cyanotic heart disease (CHD) in children is associated with several complications, amongst these complications is growth retardation which is believed to be multifactorial. Objectives: The objective of this study is to find out the role of leptin and Insulin-Like Growth Factor-1 (IGF-1) in the growth of paediatric patients with cyanotic CHD of different anatomical defects. Design/Methods: This is a cross-sectional study involving thirty-nine children known to suffer from congenital cyanotic heart disease followed by the cardiology outpatient department, and forty-seven matched controls. Serum leptin and IGF-1 were evaluated in all the enrolled subjects besides anthropometric measurement and assessment of average oxygen saturation. Results: The patients' group showed statistically significant lower height, weight, Body mass index (BMI), leptin levels, and IGF-1. In addition, the patient group had a significant positive correlation between serum leptin and BMI, as well as a positive correlation of IGF-1 with average oxygen saturation. Conclusion: Children suffering from congenital cyanotic heart disease have a higher probability of developing poor growth. Serum leptin and IGF-1 are lower in affected children with congenital cyanotic cardiac defects suggesting that they may play a role in their poor growth. [ABSTRACT FROM AUTHOR]

Background: Although several studies have examined patients who have undergone transcatheter fenestration closure, comprehensive evaluations of its long-term outcomes remain scarce. Therefore, this study aimed to evaluate the clinical status of these patients after a long-term follow-up period. Methods: This cross-sectional analytical study evaluated the records of all children with congenital heart diseases admitted for transcatheter fenestration closure at Rajaie Cardiovascular Medical and Research Center, a tertiary care hospital specializing in congenital heart diseases in Tehran, Iran. We included patients with a history of fenestration following Fontan surgery who required fenestration closure between January 2012 and August 2020. Cardiac function data, such as ejection fraction (EF), pulmonary artery pressure (PAP), and O2 saturation, were extracted from electronic medical records. Results: We assessed 26 patients (11 female and 15 male) with a mean age of 13.88±3.73 years. Comparing EF before and after fenestration closure revealed a significant difference (P=0.011), with only 2 patients (7.7%) experiencing a slight reduction (5.0%) in EF. No significant difference was observed in PAP before and after closure (P=0.068), although most patients (n=16, 61.5%) had a postprocedural reduction. Our results demonstrated a significant difference before and after the procedure (P<0.001), with all patients exhibiting increased O2 saturation after closure. Conclusion: Our study demonstrated improvements in cardiovascular function and desirable organ function among patients. These findings suggest that transcatheter fenestration closure could serve as a beneficial complementary approach for patients with patent fenestration. [ABSTRACT FROM AUTHOR]

Objective: Shone's complex comprises of a combination of congenital cardiac anomalies causing obstructions in the left ventricle's inflow and outflow tracts. This systematic review aims to evaluate the clinical features and surgical outcomes of Shone's complex. Methods: An electronic literature search of PubMed and Scopus was performed to identify relevant studies related to the presentation, management, and outcomes of Shone's complex. Two reviewers independently performed selection. Data on study characteristics, participant demographics, interventions, outcomes, and follow-up durations were extracted and analyzed. Results: A total of 691 papers were identified, with 18 studies included in the final analysis. The majority of the studies (n = 12) focused on the pediatric age group. The most common clinical presentations were coarctation of the aorta (n = 17) and mitral stenosis (n = 12). Surgical interventions often involved staged approaches, prioritizing outflow before inflow obstructions. Mitral valve repair was preferred over replacement due to better long-term outcomes (n = 8). Biventricular repair was recommended due to improved postoperative outcomes, but often needed reoperations. Reoperations were common, primarily due to recurrent coarctation (n = 10), subaortic stenosis (n = 8), and mitral valve dysfunction (n = 7). Pulmonary hypertension (n = 10) and arrhythmias (n = 11) were significant complications. Most patients were in modified Ross/NYHA functional class 1 on follow-up. Mortality rates ranged from 4 to 28%, with better outcomes associated with early and strategic surgical interventions. Conclusion: Early diagnosis and biventricular repair were associated with better outcomes while transplantation was often an eventuality. Standardized diagnostic criteria, long-term follow-up, and consensus guidelines are needed to improve the management of this congenital heart disease. [ABSTRACT FROM AUTHOR]

Maternal diabetes mellitus is among the most frequent environmental contributors to congenital birth defects, including heart defects and craniofacial anomalies, yet the cell types affected and mechanisms of disruption are largely unknown. Using multi-modal single cell analyses, here we show that maternal diabetes affects the epigenomic landscape of specific subsets of cardiac and craniofacial progenitors during embryogenesis. A previously unrecognized cardiac progenitor subpopulation expressing the homeodomain-containing protein ALX3 showed prominent chromatin accessibility changes and acquired a more posterior identity. Similarly, a subpopulation of neural crest-derived cells in the second pharyngeal arch, which contributes to craniofacial structures, displayed abnormalities in the epigenetic landscape and axial patterning defects. Chromatin accessibility changes in both populations were associated with increased retinoic acid signaling, known to establish anterior-posterior identity. This work highlights how an environmental insult can have highly selective epigenomic consequences on discrete cell types leading to developmental patterning defects.

A common feature of congenital heart disease is the presence of right ventricular outflow tract (RVOT) obstruction that can range from mild to severe and can lead to atresia of the pulmonary valve, in extreme conditions. RVOT abnormalities can frequently be corrected surgically or via interventional means. However, most of these patients will ultimately develop pulmonary valve insufficiency and eventual right ventricular dilation, which will require a pulmonary valve replacement at some point in their life to mitigate the detrimental effects of pulmonary valve regurgitation (PVR) on the right ventricle (RV). The evolution from the studies done by Philip Bonhoeffer to implant a pulmonary valve via transcatheter means, have provided a bedrock for transcatheter pulmonary valve replacement (TPVR). Yet, several areas of unmet need for a demographic of patients still exist. Here, we discuss the clinical unmet needs in children under 20 Kg and expand the use of hybrid and other TPVR approaches along with the current indications and contraindications for pulmonary valve replacement. The constraints and limitations from commercially available pulmonary valves will be discussed from a clinical standpoint. Finally, we explore the use of hybrid and periventricular delivery of transcatheter pulmonary valves in younger patients.

The risk of congenital heart defects (CHDs) may be influenced by maternal genes, fetal genes, and their interactions. Existing methods commonly test the effects of maternal and fetal variants one-at-a-time and may have reduced statistical power to detect genetic variants with low minor allele frequencies. In this article, we propose a gene-based association test of interactions for maternal-fetal genotypes (GATI-MFG) using a case-mother and control-mother design. GATI-MFG can integrate the effects of multiple variants within a gene or genomic region and evaluate the joint effect of maternal and fetal genotypes while allowing for their interactions. In simulation studies, GATI-MFG had improved statistical power over alternative methods, such as the single-variant test and functional data analysis (FDA) under various disease scenarios. We further applied GATI-MFG to a two-phase genome-wide association study of CHDs for the testing of both common variants and rare variants using 947 CHD case mother-infant pairs and 1306 control mother-infant pairs from the National Birth Defects Prevention Study (NBDPS). After Bonferroni adjustment for 23,035 genes, two genes on chromosome 17, TMEM107 (p = 1.64e-06) and CTC1 (p = 2.0e-06), were identified for significant association with CHD in common variants analysis. Gene TMEM107 regulates ciliogenesis and ciliary protein composition and was found to be associated with heterotaxy. Gene CTC1 plays an essential role in protecting telomeres from degradation, which was suggested to be associated with cardiogenesis. Overall, GATI-MFG outperformed the single-variant test and FDA in the simulations, and the results of application to NBDPS samples are consistent with existing literature supporting the association of TMEM107 and CTC1 with CHDs.

ABSTRACT Objective: 3p deletion syndrome is a rare monosomal disease that encompasses deletions throughout the short arm of chromosome 3. It is often in the distal region (3p25-pter), but variations in breakpoints and a complex clinical manifestation exist, with congenital heart defects being considered rare. We present the first case of hypoplastic left heart syndrome and minor dysmorphic features associated with 3p- syndrome. Furthermore, we aim to establish a gene-phenotype association. Case description: The diagnosis was made by karyotyping, followed by a literature investigation and in silico bioinformatic analysis about the possible candidate genes associated with congenital heart defects or hypoplastic left heart syndrome in 3p- syndrome. All genes analyzed that could affect heart formation are located in the 3p25.3 region, adjacent to the deleted region in the newborn from our case (3p26). Taking into account the technical limitations of the karyotype and the strength of evidence from each gene evaluated and locus proximity, it is likely that an unidentified partial break in the CAV3 gene occurred. Comments: We identified an indirect relation between gene CAV3 and hypoplastic left heart syndrome due to its strong association with cardiomyopathies and isolated cardiac defects. Furthermore, the cytogenetic band from our case is new information for the delimitation of a critical cardiac region on 3p syndrome, a discussion that has been ongoing since 1986. Thus, we reinforce the importance of cytogenetic investigation in patients with hypoplastic hearts and dysmorphia, assisting in diagnosis, definition of prognosis, and genetic counseling for the family.

BackgroundPediatric heart transplant candidates on the waitlist have the highest mortality rate among all solid organ transplants. A risk score incorporating a candidate's individual risk factors may better predict mortality on the waitlist and optimize organ allocation to the sickest of those awaiting transplant.MethodsUsing the United Network for Organ Sharing (UNOS) database, we evaluated a total of 5542 patients aged 0-18 years old on the waitlist for a single, first time, heart transplant from January 2010 to June 2019. We performed a univariate analysis on two-thirds (N = 3705) of these patients to derive the factors most associated with waitlist mortality or delisting secondary to deterioration within 1 year. Those with a p

OBJECTIVES: Patients with congenital heart disease (CHD) are increasingly pursuing pregnancy, highlighting the need for data on late cardiovascular events (more than 6 months after delivery). We aimed to determine the incidence of late cardiovascular events in postpartum patients with CHD and evaluate the accuracy of the existing risk scores in predicting these events. STUDY DESIGN: We identified patients with CHD who delivered between 2008 and 2020 at a tertiary centre and had follow-up data for greater than 6 months post partum. Late cardiovascular events were defined as heart failure, arrhythmia, thromboembolic events, endocarditis, urgent cardiovascular interventions or death. Survival analysis and Cox proportional model were used to estimate the incidence of late cardiovascular events and determine the hazard ratio of factors associated with these events. RESULTS: Of 117 patients, 19% had 36 late cardiovascular events over a median follow-up of 3.8 years. Annual incidence of any late cardiovascular event was 5.7%. Hazards of late cardiovascular events were significantly higher among those with higher Cardiac Disease in Pregnancy Study (CARPREG) II and Zwangerschap bij Aangeboren HARtAfwijking-Pregnancy in Women With Congenital Heart Disease (ZAHARA) risk scores and among patients with prepregnancy New York Heart Association class≥II. C-statistic to predict the late cardiovascular events was highest for ZAHARA (0.7823), followed by CARPREG II (0.6902) and prepregnancy New York Heart Association class≥ II (0.6677). CONCLUSIONS: Currently available risk tools designed for prognostication during the peripartum period can also be used to determine risks of late maternal cardiovascular events among those with CHD. These findings provide important new information for counselling and risk modification.

BackgroundCharacterization of brain injury and neurodevelopmental (ND) outcomes in critical congenital heart disease (cCHD) has primarily focused on hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). This study reports brain injury and ND outcomes among patients with heterogeneous cCHD diagnoses beyond HLHS and TGA.MethodsThis prospective cohort study included infants with HLHS, TGA, or heterogenous "Other cCHD" including left- or right-sided obstructive lesions, anomalous pulmonary venous return, and truncus arteriosus. Brain injury on perioperative brain MRI and ND outcomes on the Bayley-II at 30 months were compared.ResultsA total of 218 participants were included (HLHS = 60; TGA = 118; "Other cCHD" = 40, including 8 with genetic syndromes). Pre-operative (n = 209) and post-operative (n = 189) MRI showed similarly high brain injury rates across groups, regardless of cardiopulmonary bypass exposure. At 30 months, participants with "Other cCHD" had lower cognitive scores (p = 0.035) compared to those with HLHS and TGA, though worse ND outcome in this group was driven by those with genetic disorders.ConclusionsFrequency of brain injury and neurodevelopmental delay among patients with "Other cCHD" is similar to those with HLHS or TGA. Patients with all cCHD lesions are at risk for impaired outcomes; developmental and genetic screening is indicated.ImpactThis study adds to literature on risk of brain injury in patients with critical congenital heart disease (cCHD) diagnoses other than hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), a heterogenous cohort of patients that has often been excluded from imaging studies. Children with cCHD beyond HLHS and TGA have similarly high rates of acquired brain injury. The high rate of neurodevelopmental impairment in this heterogenous group of cCHD diagnoses beyond HLHS and TGA is primarily driven by patients with comorbid genetic syndromes such as 22q11.2 deletion syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We performed whole genome sequencing (WGS) on 183 HLHS patient-parent trios to identify candidate genes, which were functionally tested in the Drosophila heart model. Bioinformatic analysis of WGS data from an index family of a HLHS proband born to consanguineous parents prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of them, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. These defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complexs role in maintaining cristae morphology and ETC assembly. Five additional HLHS probands harbored rare, predicted damaging variants in CHCHD3 or CHCHD6. Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes from these patients for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 (goliath, E3 ubiquitin ligase), or SPTBN1 (β-Spectrin, scaffolding protein) caused synergistic heart defects, suggesting the likely involvement of diverse pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.

Cardiac malformations are sporadically diagnosed in domestic species; however, little literature is available for this group of developmental anomalies in goats. We performed a retrospective study to catalog congenital cardiac conditions in goats submitted to the University of California-Davis, Veterinary Medical Teaching Hospital, Anatomic Pathology Autopsy Service. From 2000 to 2021, of 1,886 goat autopsies, 29 cases of cardiac malformations were identified (1.5%). Thirteen were ≤ 2-wk-old, 8 were 1-6-mo-old, and 8 were adults 2-9-y-old. The most common malformations were ventricular septal defect (VSD; 21 of 29), atrial septal defect or persistent foramen ovale (10 of 29), and double-outlet right ventricle (3 of 29). Nine cases had > 1 malformation, typically including a VSD. Conditions that had not been reported in the goat included double-outlet right ventricle (3), tetralogy of Fallot (1), cor triatriatum sinister (1), and mitral valve dysplasia (1). Two adult cases were incidental and not suspected clinically. Cardiac malformations occur not uncommonly in goats and should be considered in a wide age range.

Introduction: Anticoagulant use in specific clinical scenarios such as venous thromboembolic disease or atrial fibrillation is common, with clearly established management guidelines. However, there is currently no unified clinical guidance for managing thrombosis in unusual scenarios, presenting a significant therapeutic challenge. Objective: To review the indications for anticoagulation and their regimens in unusual clinical situations based on available evidence. Methods: A literature review was conducted from 1997 to 2022, using relevant MeSH terms for anticoagulation, oral anticoagulants, embolism, and thrombosis. Information was extracted and synthesized in a structured manner. Results: In nephrotic syndrome, warfarin is recommended, although alter-natives such as low molecular weight heparins, aspirin, or direct oral anti-coagulants exist. For intracavitary thrombus, warfarin is the drug of choice, with demonstrated equivalent efficacy to direct oral anticoagulants. For peripheral arterial disease, rivaroxaban at vascular protection dose + aspirin has shown benefit in major adverse cardiovascular outcomes depending on individual profile. Conclusions: Management of these scenarios requires proper clinical assessment and selection of the type of anticoagulant, ensuring maximum reduction of both thrombosis and bleeding risks.

Abstract Background Congenital tracheal stenosis is a rare structural obstructive disorder affecting a segment of the trachea. It is often caused by complete or nearly complete cartilaginous rings narrowing the airway. Approximately 50% of cases are associated with abnormal left pulmonary artery rings. Case presentation We present the case of a 4-month-old female infant with complex congenital tracheal stenosis associated with a left pulmonary artery vascular ring and congenital heart disease. The patient underwent successful surgical intervention involving repair of the congenital heart defect and reimplantation of the pulmonary artery, followed by sliding tracheoplasty in one surgery procedure. Postoperative outcomes were favorable, with successful extubating and resolution of respiratory symptoms. Conclusions Sliding tracheoplasty proved an effective treatment option in this complex case, highlighting its reproducibility and favorable outcomes in managing congenital tracheal stenosis.

SOX7 is a transcription factor-encoding gene located in a region on chromosome 8p23.1 that is recurrently deleted in individuals with ventricular septal defects (VSDs). We have previously shown that Sox7-/- embryos die of heart failure around E11.5. Here, we demonstrate that these embryos have hypocellular endocardial cushions with severely reduced numbers of mesenchymal cells. Ablation of Sox7 in the endocardium also resulted in hypocellular endocardial cushions, and we observed VSDs in rare E15.5 Sox7flox/-;Tie2-Cre and Sox7flox/flox;Tie2-Cre embryos that survived to E15.5. In atrioventricular explant studies, we showed that SOX7 deficiency leads to a severe reduction in endocardial-to-mesenchymal transition (EndMT). RNA-seq studies performed on E9.5 Sox7-/- heart tubes revealed severely reduced Wnt4 transcript levels. Wnt4 is expressed in the endocardium and promotes EndMT by acting in a paracrine manner to increase the expression of Bmp2 in the myocardium. Both WNT4 and BMP2 have been previously implicated in the development of VSDs in individuals with 46,XX sex reversal with dysgenesis of kidney, adrenals and lungs (SERKAL) syndrome and in individuals with short stature, facial dysmorphism and skeletal anomalies with or without cardiac anomalies 1 (SSFSC1) syndrome, respectively. We now show that Sox7 and Wnt4 interact genetically in the development of VSDs through their additive effects on endocardial cushion development with Sox7+/-;Wnt4+/- double heterozygous embryos having hypocellular endocardial cushions and perimembranous and muscular VSDs not seen in their Sox7+/- and Wnt4+/- littermates. These results provide additional evidence that SOX7, WNT4 and BMP2 function in the same pathway during mammalian septal development and that their deficiency can contribute to the development of VSDs in humans.

BACKGROUND: Congenital heart disease (CHD) is highly heritable, but the power to identify inherited risk has been limited to analyses of common variants in small cohorts. METHODS: We performed reimputation of 4 CHD cohorts (n=55 342) to the TOPMed reference panel (freeze 5), permitting meta-analysis of 14 784 017 variants including 6 035 962 rare variants of high imputation quality as validated by whole genome sequencing. RESULTS: Meta-analysis identified 16 novel loci, including 12 rare variants, which displayed moderate or large effect sizes (median odds ratio, 3.02) for 4 separate CHD categories. Analyses of chromatin structure link 13 of the genome-wide significant loci to key genes in cardiac development; rs373447426 (minor allele frequency, 0.003 [odds ratio, 3.37 for Conotruncal heart disease]; P=1.49×10-8) is predicted to disrupt chromatin structure for 2 nearby genes BDH1 and DLG1 involved in Conotruncal development. A lead variant rs189203952 (minor allele frequency, 0.01 [odds ratio, 2.4 for left ventricular outflow tract obstruction]; P=1.46×10-8) is predicted to disrupt the binding sites of 4 transcription factors known to participate in cardiac development in the promoter of SPAG9. A tissue-specific model of chromatin conformation suggests that common variant rs78256848 (minor allele frequency, 0.11 [odds ratio, 1.4 for Conotruncal heart disease]; P=2.6×10-8) physically interacts with NCAM1 (PFDR=1.86×10-27), a neural adhesion molecule acting in cardiac development. Importantly, while each individual malformation displayed substantial heritability (observed h2 ranging from 0.26 for complex malformations to 0.37 for left ventricular outflow tract obstructive disease) the risk for different CHD malformations appeared to be separate, without genetic correlation measured by linkage disequilibrium score regression or regional colocalization. CONCLUSIONS: We describe a set of rare noncoding variants conferring significant risk for individual heart malformations which are linked to genes governing cardiac development. These results illustrate that the oligogenic basis of CHD and significant heritability may be linked to rare variants outside protein-coding regions conferring substantial risk for individual categories of cardiac malformation.

BACKGROUND: Known genetic causes of congenital heart disease (CHD) explain

BackgroundCOVID-19 infection is generally regarded as an acute self-limiting illness in children, but it can cause significant morbidity and mortality in both healthy and high-risk children. There are limited data on the outcomes of children with congenital heart disease (CHD) and COVID-19. This study aimed to examine the risks of mortality, in-hospital cardiovascular and non-cardiovascular complications in this patient population.MethodsWe analyzed data from hospitalized pediatric patients from 2020 using the nationally representative National Inpatient Sample (NIS). Children hospitalized for COVID-19 were included, and weighted data were used to compare in-hospital mortality and morbidities between children with and without CHD.ResultsOut of 36,690 children admitted with a diagnosis of COVID-19 infection(ICD-10 code:U07.1 and B97.29) during calendar year 2020, 1240 (3.4%) had CHD. The risk of mortality in children with CHD was not significantly higher than those without CHD(1.2% vs. 0.8%, p = 0.50), with adjusted OR (aOR) of 1.7 (95% CI: 0.6-5.3). Tachyarrhythmias and heart block were more likely in CHD children with an aOR of 4.2 (95% CI: 1.8-9.9) and aOR of 5.0 (95% CI: 2.4-10.8), respectively. Similarly, respiratory failure [aOR = 2.0 (1.5-2.8)], respiratory failure requiring non-invasive mechanical ventilation [aOR = 2.7 (1.4-5.2)] and invasive mechanical ventilation [aOR = 2.6 (1.6-4.0)], and acute kidney injury [aOR = 3.4 (2.2-5.4)] were all significantly higher among patients with CHD. Median length of hospital stay in children with CHD was longer than those without CHD [5 days (IQR: 2-11) vs. 3 days (IQR: 2-5), p =

BackgroundDespite guidelines recommending narrow-spectrum perioperative antibiotics (NSPA) as prophylaxis for most children undergoing congenital heart disease (CHD) surgery, broad-spectrum perioperative antibiotics (BSPA) are variably used, and their impact on postoperative outcomes is poorly understood.MethodsWe used administrative data from U.S. hospitals participating in the Vizient Clinical Data Base. Admissions from 2011 to 2018 containing a qualifying CHD surgery in children 0-17 years old were evaluated for exposure to BSPA versus NSPA. Propensity score-adjusted models were used to compare postoperative length of hospital stay (PLOS) by exposure group, while adjusting for confounders. Secondary outcomes included subsequent antimicrobial treatment and in-hospital mortality.ResultsAmong 18 088 eligible encounters from 24 U.S. hospitals, BSPA were given in 21.4% of CHD surgeries, with mean BSPA use varying from 1.7% to 96.1% between centers. PLOS was longer for BSPA-exposed cases (adjusted hazard ratio 0.79; 95% confidence interval [CI]: 0.71-0.89, P < .0001). BSPA was associated with higher adjusted odds of subsequent antimicrobial treatment (odds ratio [OR] 1.24; 95% CI: 1.06-1.48), and there was no significant difference in adjusted mortality between exposure groups (OR 2.06; 95% CI: 1.0-4.31; P = .05). Analyses of subgroups with the most BSPA exposure, including high-complexity procedures and delayed sternal closure, also did not find (but could not exclude) a measurable benefit from BSPA on PLOS.ConclusionsBSPA use was common in high-risk populations, and varied substantially between centers. Standardizing perioperative antibiotic practices between centers may reduce unnecessary broad-spectrum antibiotic exposure and improve clinical outcomes.

Background With improving survival of patients with single ventricle physiology who underwent Fontan palliation, there is also an increase in the prevalence of overweight and obesity in these patients. This tertiary care single-center study aims to determine the association of body mass index (BMI) with the clinical characteristics and outcomes in adults with Fontan. Methods and Results Adult patients (aged ≥18 years) with Fontan who were managed at a single tertiary care center between January 1, 2000, and July 1, 2019, and had BMI data available were identified via retrospective review of medical records. Univariate and multivariable (after adjusting for age, sex, functional class, and type of Fontan) linear and logistic regression, as appropriate, were utilized to evaluate associations between BMI and diagnostic testing and clinical outcomes. A total of 163 adult patients with Fontan were included (mean age, 29.9±9.08 years), with a mean BMI of 24.2±5.21 kg/m2 (37.4% of patients had BMI ≥25 kg/m2). Echocardiography data were available for 95.7% of patients, exercise testing for 39.3% of patients, and catheterization for 53.7% of patients. Each SD increase in BMI was significantly associated with decreased peak oxygen consumption (P=0.010) on univariate analysis and with increased Fontan pressure (P=0.035) and pulmonary capillary wedge pressure (P=0.037) on multivariable analysis. In addition, BMI ≥25 kg/m2 was independently associated with heart failure hospitalization (adjusted odds ratio [AOR], 10.2; 95% CI, 2.79-37.1 [P

Objective: Coarctation of the aorta (CoA) is a congenital heart defect characterized by a narrowing of the aorta, often necessitating surgical repair to restore normal blood flow. Despite successful initial interventions, a significant subset of patients experiences recoarctation (re-CoA), the reoccurrence of aortic narrowing, presenting a considerable clinical challenge. This study aims to investigate the triggers or contributing factors associated with the development of re-CoA following the initial repair of CoA, to identify potential strategies for its prevention and management. Methods: A retrospective cohort study includes information about 120 patients, who underwent 4 different types of surgical repairs of CoA through left thoracotomy between 2012-2022. Recoarctation was evaluated using the pressure gradient on the coarctation site measured by echocardiography. A threshold of more than 20mmHg was employed to define recoarctation. All statistical analysis was performed using SPSS software. Results: The study revealed that 30 patients (25%) experienced early recoarctation, while 52 patients (43.7%) encountered late recoarctation. Patient-related variables such as age, height, weight, gender, and body mass index (BMI) were not correlated with early or late recoarctation. Among the 28 patients (23.3%) who had arch hypoplasia, 12 of them experienced early recoarctation, and 22 of them exhibited late recoarctation. Correlation tests demonstrated a strong negative correlation of the Z-score of the arch size with both early recoarctation (r=-0.229, p=0.013) and late recoarctation (r=-0.421, p<0.001). Resection and end-to-end anastomosis (EEA) displayed the highest proportions of early (59%) and late (77%) recoarctation. Prosthetic patch aortoplasty (PPA) showed a relatively higher rate of recoarctation, with 27% of patients experiencing early recoarctation and 44% exhibiting late recoarctation. Resection and extended end-to-end anastomosis displayed a comparatively lower rate, with 0% experiencing early recoarctation and 23% exhibiting late recoarctation. Conclusion: Aortic arch hypoplasia emerges as a significant factor for both early and late recoarctation. Additionally, while all coarctation repair methods carry some risk of recoarctation, resection and end-to-end anastomosis and prosthetic patch aortoplasty may pose a higher risk compared to extended end-to-end anastomosis. Recognizing these factors is crucial for optimizing surgical outcomes and reducing recoarctation incidence in patients with coarctation of the aorta. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the associated implications and outcomes of diaphragmatic paralysis following pediatric cardiac surgery at a center specializing in congenital heart diseases. Methods: The eligibility criteria for this cross-sectional study included patients who underwent surgery between January 2020 and June 2021. We collected sociodemographic, anthropometric, cardiac diagnostic, surgical, diaphragmatic paralysis diagnostic, ventilatory, and temporal variables and those related to the outcome of diaphragmatic paralysis and hospital outcomes. We conducted descriptive and inferential (logistic regression model) statistical analysis. Results: Among a total of 246 patients, a prevalence of 2.4% of diaphragmatic paralysis was estimated, predominantly in those with cyanotic congenital heart disease. Patients with extubation failure were 3.59 times more likely to have diaphragmatic paralysis (p<0.05). The need for non-invasive ventilation increased the patient's chance of being diagnosed with diaphragmatic paralysis by 14 times (OR=14.29, p>0.05). Unilateral diaphragm injury and the necessity for surgical treatment by plication were predominant. All patients with diaphragmatic paralysis were in the intensive care unit discharged. Conclusion: Extubation failure and non-invasive support were associated with diaphragmatic paralysis. Outcomes included diaphragmatic plication and subsequent discharge from the intensive care unit. [ABSTRACT FROM AUTHOR]

Currently, nearly 90% of patients with congenital heart disease (CHD) reach adulthood in relatively good health. Structured transition programs have emerged to support adolescents and young adults in transitioning to adult care structures, improve their autonomy, and limit healthcare ruptures. The TRANSITION-CHD randomized controlled trial aimed to assess the impact of a transition program on health-related quality of life (HRQoL) in adolescents and young adults with CHD. From January 2017 to February 2020, 200 subjects with a CHD, aged 13–25 years, were enrolled in a prospective, controlled, multicenter study and randomized in two balanced groups (transition program vs. standard of care). The primary outcome was the change in PedsQL self-reported HRQoL score between baseline and 12-month follow-up, using an intention-to-treat analysis. The secondary outcomes were the change in disease knowledge, physical health (cardiopulmonary fitness, physical activity), and mental health (anxiety, depression). The change in HRQoL differed significantly between the transition group and the control group (mean difference = 3.03, 95% confidence interval (CI) = [0.08; 5.98]; p =.044; effect size = 0.30), in favor of the intervention group. A significant increase was also observed in the self-reported psychosocial HRQoL (mean difference = 3.33, 95% CI = [0.01; 6.64]; p =.049; effect size = 0.29), in the proxy-reported physical HRQoL (mean difference = 9.18, 95% CI = [1.86; 16.51]; p =.015; effect size = 0.53), and in disease knowledge (mean difference = 3.13, 95% CI = [1.54; 4.72]; p <.001; effect size = 0.64). The TRANSITION-CHD program improved HRQoL and disease knowledge in adolescents and young adults with CHD, supporting the generalization and systematization of similar preventive interventions in pediatric and congenital cardiology. [ABSTRACT FROM AUTHOR]

Objectives: We assessed reporting misclassification for 12 critical congenital heart defects (CCHDs) identified through administrative diagnosis codes within a passive surveillance system. We measured the effect of misclassification on prevalence estimation. Lastly, we investigated a sample‐based review strategy to estimate surveillance misclassification resulting from administrative diagnosis codes for case detection. Methods: We received 419 reports of CCHDs between 2007 and 2018; 414 were clinically reviewed. We calculated confirmation probabilities to assess misclassification and adjust prevalence estimates. Random samples of reported cases were taken at proportions between 20% and 90% for each condition to assess sample bias. Sampling was repeated 1000 times to measure sample‐estimate variability. Results: Misclassification ranged from a low of 19% (n = 4/21) to a high of 84% (n = 21/25). Unconfirmed prevalence rates ranged between one and six cases per 10,000 live births, with some conditions significantly higher than national estimates. However, confirmed rates were either lower or comparable to national estimates. Conclusion: Passive birth defect surveillance programs that rely on administrative diagnosis codes for case identification of CCHDs are subject to misclassification that bias prevalence estimates. We showed that a sample‐based review could improve the prevalence estimates of 12 cardiovascular conditions relative to their unconfirmed prevalence rates. [ABSTRACT FROM AUTHOR]

BACKGROUND: Waitlist mortality (WM) remains elevated in pediatric heart transplantation. Allocation policy is a potential tool to help improve WM. This study aims to identify patients at highest risk for WM to potentially inform future allocation policy changes. METHODS: The Pediatric Heart Transplant Society database was queried for patients <18 years of age indicated for heart transplantation between January 1, 2010 to December 31, 2021. Waitlist mortality was defined as death while awaiting transplant or removal from the waitlist due to clinical deterioration. Because WM is low after the first year, analysis was limited to the first 12 months on the heart transplant list. Kaplan-Meier analysis and log-rank testing was conducted to compare unadjusted survival between groups. Cox proportional hazard models were created to determine risk factors for WM. Subgroup analysis was performed for status 1A patients based on body surface area (BSA) at time of listing, cardiac diagnosis, and presence of mechanical circulatory support. RESULTS: In total 5974 children met study criteria of which 3928 were status 1A, 1012 were status 1B, 963 were listed status 2, and 65 were listed status 7. Because of the significant burden of WM experienced by 1A patients, further analysis was performed in only patients indicated as 1A. Within that group of patients, those with smaller size and lower eGFR had higher WM, whereas those patients without congenital heart disease or support from a ventricular assist device (VAD) at time of listing had decreased WM. In the smallest size cohort, cardiac diagnoses other than dilated cardiomyopathy were risk factors for WM. Previous cardiac surgery was a risk factor in the 0.3 to 0.7 m2 and >0.7 m2 BSA groups. VAD support was associated with lower WM other than in the single ventricle cohort, where VAD was associated with higher WM. Extracorporeal membrane oxygenation and mechanical ventilation were associated with increased risk of WM in all cohorts. CONCLUSIONS: There is significant variability in WM among status-1A patients. Potential refinements to current allocation system should factor in the increased WM risk we identified in patients supported by extracorporeal membrane oxygenation or mechanical ventilation, single ventricle congenital heart disease on VAD support and small children with congenital heart disease, restrictive cardiomyopathy, or hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Congenital tracheal stenosis is a rare structural obstructive disorder affecting a segment of the trachea. It is often caused by complete or nearly complete cartilaginous rings narrowing the airway. Approximately 50% of cases are associated with abnormal left pulmonary artery rings. Case presentation: We present the case of a 4-month-old female infant with complex congenital tracheal stenosis associated with a left pulmonary artery vascular ring and congenital heart disease. The patient underwent successful surgical intervention involving repair of the congenital heart defect and reimplantation of the pulmonary artery, followed by sliding tracheoplasty in one surgery procedure. Postoperative outcomes were favorable, with successful extubating and resolution of respiratory symptoms. Conclusions: Sliding tracheoplasty proved an effective treatment option in this complex case, highlighting its reproducibility and favorable outcomes in managing congenital tracheal stenosis. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD), which accounts for about one-third of all congenital birth defects and affects about 1% of all live births worldwide, has had a stable incidence rate and decreased mortality rate since 1990. Despite advances in fetal cardiac ultrasound examinations and routine pulse oximetry screening of newborns, a considerable proportion of patients with CHD may still be missed until adulthood, leading to major morbidity and mortality due to physical limitations and reduced quality of life. We herein describe a 29-year-old woman who was mistaken as an inoperable case of CHD and referred to our center with palpitation and exertional dyspnea. During workups, she was diagnosed with severe pulmonary hypertension associated with patent ductus arteriosus (PDA), pre-ductal aortic coarctation, ventricular septal defect (VSD), and bicuspid aortic valve, all of which had been missed from infancy. After initial medical treatment for pulmonary hypertension, a simultaneous transcatheter approach was selected, whereby the PDA was closed with an occluder device, and the coarctation was repaired simultaneously with a self-expanding stent. Eight months later, her VSD was closed successfully via an interventional technique using a muscular VSD occluder device. This case highlights the significance of adult CHD fellowship training. A cardiologist specialized in this field was able to properly diagnose and treat an adult with complex CHD, which had been overlooked since infancy. As a result, the patient experienced complete relief from her symptoms and was saved from developing Eisenmenger syndrome. [ABSTRACT FROM AUTHOR]

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INTRODUCTION: Cardiovascular malformations are the most prevalent in newborns (NB). The prevalence of congenital heart disease (CHD) in Brazil has increased in recent years. The pulse oximetry test is currently used for the early diagnosis of CHD. OBJECTIVE: Analyze data on the pulse oximetry test carried out in the Rooming Room of a Tertiary Hospital as a screening for the diagnosis of critical congenital heart disease (CCHD), from January 2015 to July 2018. METHODOLOGY: Observational, quantitative and cross-sectional research through the analysis of data from the results of pulse oximetry test carried out at the service and research in electronic medical records of patients who had an altered test. RESULTS: 10,053 tests were carried out in the period with 42 changes. Of these, 15 (35.7%) had normal exams after repeating the heart test and/or performing the echocardiogram; 11 (26.2%) found heart disease on echocardiography; 13 (31%) did not repeat the heart test or did not perform an echocardiogram; 3 (7.1%) were not found. Echocardiograms were performed on 20 patients, with findings of heart disease found in 11 (false positive rate of 0.2% for pulse oximetry test). CCHD was observed in only 1 (Ebsteins Anomaly). The other findings were of acyanotic or pulmonary heart disease. CONCLUSION: It was evident that pulse oximetry test contributed to the diagnosis of CCC, to the realization of other diagnoses of CCC, as well as the need to correctly follow the protocol recommended by the SBP as a way to reduce hospitalization costs and echocardiograms.