Search Results (112)

The development and function of the heart are governed by a highly coordinated network of regulatory mechanisms, among which miRNAs play a central role. These small, non-coding molecules modulate gene expression predominantly through mRNA degradation. This narrative review aims to summarize current knowledge about biogenesis, its impact on heart development and function, and its clinical implications in pediatric cardiology. We discuss how specific miRNAs contribute to shaping the normal heart and influencing the pathogenesis of congenital malformations. Furthermore, we review disease-specific miRNA signatures identified in the most common congenital heart defects and some acquired diseases, including hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), bicuspid aortic valve (BAV), septation defects, cardiomyopathies, arrhythmias, and myocarditis. Many studies indicate that circulating and tissue miRNAs can become non-invasive biomarkers for early diagnosis and disease monitoring. Experimental data suggest their potential use in treatment despite many delivery and safety challenges. However, further research is necessary to fully exploit the potential of miRNAs and effectively translate these findings into clinical practice in pediatric cardiology. Full article

Congenital heart disease (CHD) is associated with neurodevelopmental and cognitive impairments, but the underlying molecular mechanisms remain unclear. This study investigated cardiac neuronal genomics in CHD using single-nucleus RNA-sequencing data (GSE203274) from 157,273 cardiac nuclei of healthy donors and patients with hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), dilated (DCM), and hypertrophic (HCM) cardiomyopathies. The Uniform Manifold Approximation and Projection (UMAP) clustering identified major cardiac cell types, revealing neuron-specific transcriptional programmes. Neuronal populations showed enriched expression of neurodevelopmental disorder-linked genes (NRXN3, CADM2, ZNF536) and synaptic signalling pathways. CHD cardiac neurons exhibited upregulated markers of cognitive dysfunction (APP, SNCA, BDNF) and neurodevelopment regulators (DNMT1, HCFC1) across subtypes. Cardiomyocyte troponin elevation correlated with neuronal exosome receptor expression (TLR2, LRP1), suggesting intercellular communication. Gene ontology analysis highlighted overlaps between cardiovascular disease pathways and neurodevelopmental disorder signatures in CHD neurons. These findings provide the first neuro-genomic map of cardiac neurons in CHD, linking cardiac pathology to neural outcomes through transcriptional dysregulation. Further, the systemic analysis of clinical findings in CHD further supports the risk of neurodevelopmental impacts. In summary, this study identifies transcriptional dysregulation within cardiac neurons in CHD and, together with a systemic analysis of clinical data, provides molecular evidence linking cardiac pathology to neurodevelopmental and cognitive impairments. Full article

Background/Objectives: This study aimed to investigate the prevalence of liver damage and its associated non-invasive markers and echocardiographic risk factors in patients who underwent surgery for congenital heart disease. Methods: This retrospective observational study was conducted at a single tertiary-care university hospital in Niigata, Japan. Of 142 patients (ventricular septal defect [VSD] n = 47, tetralogy of Fallot [TOF] n = 67, Fontan n = 28), 52.8% were male [median age: 22.7 years; VSD (24.3 years), TOF (24.0 years), and Fontan (12.5 years)]. Pediatric patients with liver diseases unrelated to congestive liver disease, such as viral hepatitis and alcoholic liver disease, were excluded. We compared non-invasive liver fibrosis age-invariant biomarkers, such as the aspartate aminotransferase-to-platelet ratio index (APRI), and various serum markers and echocardiographic parameters to assess the prevalence and predictors of hepatic fibrosis. Results: The Fontan circulation group had the highest APRI, followed by the TOF group, while the VSD group had a low risk of APRI elevation. Postoperative TOF patients required monitoring for cirrhosis progression. Inferior vena cava mobility was associated with echocardiographic parameters and fibrosis severity, along with a loss of respiratory variability. The limitations of other cardiac assessments were highlighted by poor anatomical measurements. Gamma-glutamyl transpeptidase (γ-GTP) demonstrated strong discriminatory ability. The optimal cutoff value was 53.0 U/L, suggesting its use as a clinical marker. Conclusions: Assessing fibrosis is crucial in CHD patients, especially those with late post-TOF repair findings. Non-invasive markers (APRI, γ-GTP, and B-type natriuretic peptide), along with echocardiographic findings, may help detect fibrosis early, enabling timely intervention and improving long-term outcomes. Clinical trial registration: 2020-0199. Full article

Background: Tetralogy of Fallot is a congenital heart defect that requires early surgical correction. However, in developing countries, many patients undergo delayed treatment due to limited healthcare resources. This study aims to identify risk factors for postoperative complications in humanitarian patients undergoing late Tetralogy of Fallot repair, defined as surgery performed after 12 months of age. Methods: A retrospective analysis was conducted on 115 humanitarian paediatric patients with a median age of 1444 days (approximately 4 years) who underwent complete Tetralogy of Fallot correction. In this humanitarian programme, patients from developing nations underwent surgical repair at our tertiary referral centre in a high-resource country. Postoperative complications were monitored within the first 30 days after surgery. Two multivariable logistic regression models were used to analyse pre/perioperative (Model 1) and postoperative (Model 2) risk factors for complications. Results: Complications occurred in 24.3% of patients. No deaths were recorded. In Model 1, smaller pulmonary valve annulus (OR = 0.066; p < 0.01) and the use of right ventricle to pulmonary artery conduit (OR = 13.252; p < 0.01) were significantly associated with a higher risk of complications. In Model 2, prolonged invasive ventilation time (OR = 1.068; p < 0.01) and extended hospitalisation time (OR = 1.093; p = 0.04) were significantly associated with complications. Conclusions: Late surgical correction of Tetralogy of Fallot in humanitarian paediatric patients can be performed with low mortality but carries a significant risk of postoperative complications. The predictive models provide useful tools for proactive clinical monitoring, personalised management, and optimisation of hospital resources. Full article

Our previous research identified 12 small Cajal body-specific RNAs (scaRNAs) with reduced expression in the right ventricle in infant patients with tetralogy of Fallot. Likewise, we showed that there were significant changes in mRNA processing in the RV in these patients. ScaRNAs play a crucial role in the biochemical maturation of spliceosomal RNAs (pseudouridylation and 2′-O-methylation). We showed that variations in scaRNA1 levels resulted in changes in alternative splicing in human cells. To investigate further the role that scaRNAs play in mRNA processing, we examine here the impact of knocking down scaRNA1 in quail myoblast cells (Coturnix japonica, a well-established animal model for studying embryonic development). Following the knockdown of scaRNA1, transcriptome analysis revealed that the genes Tjp1, Map3k7, and Sppl2a were alternatively spliced. Growing evidence indicates that alternative splicing of mRNA plays an important role in regulating cell differentiation and tissue development. Our data presented here provide additional support for research to clarify the specific roles that individual scaRNAs play in regulating spliceosome function and mRNA splicing. Full article

Background: The PATHFINDER-CHD Registry is a prospective, multicenter, non-interventional registry across tertiary care centers in Germany. The aim is to analyze real-world data on adults with congenital heart defects (ACHD) or hereditary connective tissue disorders who have manifest heart failure (HF), a history of HF, or are at significant risk of developing HF. This analysis investigates the prevalence and clinical impact of overweight and obesity in this unique population. Methods: As of 1st February, 2025, a total of 1490 ACHD had been enrolled. The mean age was 39.4 ± 12.4 years, and 47.9% were female. Patients were categorized according to Perloff’s functional class and the Munich Heart Failure Classification for Congenital Heart Disease (MUC-HF-Class). Results: The most common congenital heart disease (CHD) in this cohort was Tetralogy of Fallot, transposition of the great arteries, and congenital aortic valve disease. Marfan syndrome was the most common hereditary connective tissue disease. Of the patients, 46.1% were classified as overweight (32.8%) or obese (13.3%), while 4.8% were underweight. The highest prevalence of overweight (47.1%) was observed among patients who had undergone palliative surgery, whereas untreated patients showed the highest proportion of normal weight (57.2%). Cyanotic patients were predominantly of normal weight. Patients with univentricular circulation exhibited significantly lower rates of overweight and obesity (35%; p = 0.001). Overweight and obesity were statistically significantly associated with arterial hypertension, diabetes mellitus, and sleep apnea (all p < 0.001). High BMI was linked to increased use of HF-specific medications, including SGLT2 inhibitors (p = 0.040), diuretics (p = 0.014), and angiotensin receptor blockers (p = 0.005). Conclusions: The data highlight the clinical relevance of overweight and obesity in ACHD with HF, emphasizing the need for individualized prevention and treatment strategies. The registry serves as a critical foundation for the optimization of long-term care in this population. Full article

Tetralogy of Fallot (ToF) with pulmonary atresia (PA) and complete right ventricular outflow tract obstruction (RVOTO) represents one of the most critical forms of congenital heart disease in neonates. These cases require complex and timely interventions to ensure survival and optimize long-term outcomes. While surgical correction offers a favorable prognosis, the period from birth to surgery is often marked by significant hemodynamic, respiratory and nutritional challenges, particularly in neonatal intensive care units (NICUs). This study aims to outline a structured, physiology-guided approach to the preoperative management of neonates with ToF and complete RVOTO, emphasizing stabilization strategies, hemodynamic support, ventilatory management and nutritional optimization. We performed a focused literature review of practices in neonatal ToF management and illustrated our experience through two case reports highlighting divergent outcomes in infants with the same anatomical diagnosis. The management strategies covered include delivery room stabilization, the use of prostaglandins, mechanical ventilation techniques, nutritional interventions and the timing of surgical intervention. A phased, physiology-guided management strategy is the key to the successful preoperative treatment of ToF with pulmonary atresia. Optimizing hemodynamics, ensuring adequate pulmonary blood flow and supporting nutritional needs are the main drivers for growth and may reduce the time from diagnosis to surgical correction. Full article

Background: Among patients with congenital heart disease, particularly those with a history of undergoing the Fontan operation, pregnancy presents a significant maternal–fetal risk, especially when complicated by severe valvular dysfunction. Lung reperfusion syndrome (LRS) is a rare but life-threatening complication occurring following valve intervention. Multidisciplinary management, including by Cardio-Obstetrics teams, is essential for optimizing outcomes in such high-risk cases. Methods: We present the case of a 37-year-old pregnant patient with previously repaired tetralogy of Fallot (via the Fontan procedure) who presented at 24 weeks gestation with worsening severe pulmonary stenosis and right-ventricular dysfunction. The patient had been lost to cardiac follow-up for over a decade. She experienced recurrent arrhythmias, including supraventricular and non-sustained ventricular tachycardia, prompting hospital admission. A multidisciplinary team recommended transcatheter pulmonic valve replacement (TPVR), performed at 28 weeks’ gestation. Results: Post-TPVR, the patient developed acute hypoxia and hypotension, consistent with Lung Reperfusion Syndrome, necessitating intensive cardiopulmonary support. Despite initial stabilization, progressive maternal respiratory failure and fetal compromise led to an emergent cesarean delivery. The neonate’s neonatal intensive care unit (NICU) course was complicated by spontaneous intestinal perforation, while the mother required intensive care unit (ICU)-level care and a bronchoscopy due to new pulmonary findings. She was extubated and discharged in stable condition on postoperative day five. Conclusions: This case underscores the complexity of managing severe congenital heart disease and valve pathology during pregnancy. Lung reperfusion syndrome should be recognized as a potential complication following TPVR, particularly in pregnant patients with Fontan physiology. Early involvement of a multidisciplinary Cardio-Obstetrics team and structured peripartum planning are critical to improving both maternal and neonatal outcomes. Full article

Objectives: This study aimed to describe the prevalence of malnutrition and its impact on postoperative outcomes in infants and children with congenital heart diseases (CHDs) undergoing cardiac surgeries. Methods: We conducted a single-center, retrospective review of medical records of children aged 1 month to 5 years with CHDs who underwent cardiac surgery at the American University of Beirut Medical Center (AUBMC) between January 2015 and January 2017. Anthropometric data were collected and z-scores for weight-for-age (WAZ), height-for-age (HAZ), weight-for-height (WHZ), and BMI-for-age were calculated. Malnutrition was classified based on the World Health Organization (WHO) definitions and the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. The postoperative outcomes were analyzed using bivariate and multivariable models. Results: The prevalence of malnutrition was 33.8%, with children younger than 24 months having significantly higher odds of malnutrition. The most common CHDs were ventricular septal defect (VSD) and tetralogy of Fallot (TOF), with malnutrition being significantly more prevalent in the children with VSD. Malnutrition was significantly associated with a prolonged pediatric intensive care unit (PICU) stay, with underweight being the strongest predictor. Malnourished children also had a significantly longer mechanical ventilation time (median 9.0 vs. 5.0 h, p = 0.017). Lower weight-for-age (WAZ) and BMI-for-age z-scores were associated with longer hospital stay, PICU stay, and mechanical ventilation durations. Conclusions: Malnutrition is prevalent among children with CHDs and is independently associated with longer hospital and PICU stays, as well as extended mechanical ventilation. Early nutritional assessment and intervention may improve postoperative outcomes in this vulnerable population. Full article

Background: Advances in medical care of patients with tetralogy of Fallot (ToF) have significantly altered the natural course of the disease by prolonging life. Thus, our focus has now shifted to exploring the health-related quality of life (HRQoL) of those patients. This study sought to explore the HRQoL of adult patients operated on for ToF using two validated instruments—the SF-36 and EQ-5D—that highlight both physical and mental aspects of the disease. Methods: A total of 115 individuals (53 ToF patients and 60 healthy controls) were recruited for the purposes of this study. HRQoL was assessed through the SF-36 and EQ-5D instruments. Comparisons were made between ToF patients and controls with subgroup analyses based on sex and age. Results: ToF patients reported significantly poorer HRQoL in the physical domains, namely Physical Functioning, Role Physical, General Health, and Physical Component Summary of the SF-36 when compared to controls (p < 0.05). Interestingly, there was a trend towards lower Bodily Pain and better Vitality scores in ToF subjects. Age influenced HRQoL, with older respondents rating their physical health lower than younger patients and controls (p < 0.05). EQ-5D VAS scores indicated that ToF patients perceived their overall health worse than controls (80.02 vs. 86.92, p < 0.001), with Anxiety/Depression being the most frequently reported problem (45.3%). Controls reported better HRQoL than ToF patients across all SF-36 domains in both health states (EQ-5D = 1 and EQ-5D > 1), except for Bodily Pain and Vitality in EQ-5D = 1. Significant differences were observed in Physical Functioning, Role Physical, General Health, Vitality, and Physical Component Score. Notably, ToF patients with EQ-5D = 1 showed unexpectedly higher Vitality scores than controls; however, this advantage diminished significantly in the EQ-5D > 1 group. Conclusions: Adult ToF survivors experience significant physical limitations as expected, while mental health seems to remain relatively unaffected compared to healthy peers. These findings underscore the importance of HRQoL assessment in patients with congenital heart disease and the need for disease-specific HRQoL instruments. Full article

Background: Severe pulmonary regurgitation (PR) often occurs after treatment of tetralogy of Fallot with a valve ring patch, leading to enlargement and diverse morphological characteristics of the native right ventricular outflow tract (nRVOT), which increases the difficulty of transcatheter pulmonary valve replacement (TPVR). The purpose of this study was to use the TPVR simulator to help doctors improve their surgical skills by simulating the surgical process in vitro. Methods: The TPVR simulator was developed using three-dimensional (3D) printing technology under computer-aided design. In this study, the TPVR simulator was used for preoperative simulation training and teaching. First, 10 specialists were equally divided into a 3D-printed group and a non-3D-printed group, each performing one TPVR; then, another six specialists and six young surgeons were selected to complete three TPVR simulations. Results: For the 3D-printed simulation group, the over-flap time (5.22 min (range: 4.85–5.87 min) vs. 6.72 min (range: 6.12–7.70 min), p = 0.016), fluoroscopy time (15.00 min (range: 13.50–16.50 min) vs. 19.00 min (range: 17.50–21.50 min), p = 0.012), and total operative time for the five surgeons (57.00 min (range: 54.00–62.50 min) vs. 67.00 min (range: 62.00–69.50 min), p = 0.036) were shorter. In addition, the results showed significant reductions in the median over-flap time and total time required in both the expert panel and young surgeon groups (all p < 0.05). Conclusions: The reliability and validity of the TPVR simulator was initially demonstrated and has the potential to be a teaching and training tool for surgeons. Full article

One out of every hundred live births present with congenital heart abnormalities caused by the aberrant development of the embryonic cardiovascular system. The conserved zinc finger transcription factor proteins, which include GATA binding protein 5 (GATA5) and GATA binding protein (GATA6) play important roles in embryonic development and their inactivation may result in congenital heart defects (CHDs). In this study, we performed genotypic–phenotypic analyses in two families affected by right-sided CHD diagnosed by echocardiography imaging. Proband A presented with pulmonary valve stenosis, and proband B presented with complex CHD involving the right heart structures. For variant detection, we employed whole-genome single-nucleotide polymorphism (SNP) microarray and family-based whole-exome sequencing (WES) studies. Proband A is a full-term infant who was admitted to the neonatal intensive care unit (NICU) at five days of life for pulmonary valve stenosis (PVS). Genomic studies revealed a normal SNP microarray; however, quad WES analysis identified a novel heterozygous [Chr20:g.61041597C>G (p.Arg237Pro)] variant in the GATA5 gene. Further analysis confirmed that the novel variant was inherited from the mother but was absent in the father and the maternal uncle with a history of heart murmur. Proband B was born prematurely at 35 weeks gestation with a prenatally diagnosed complex CHD. A postnatal evaluation revealed right-sided heart defects including pulmonary atresia with intact ventricular septum (PA/IVS), right ventricular hypoplasia, tricuspid valve hypoplasia, hypoplastic main and bilateral branch pulmonary arteries, and possible coronary sinusoids. Cardiac catheterization yielded anatomy and hemodynamics unfavorable to repair. Hence, heart transplantation was indicated. Upon genomic testing, a normal SNP microarray was observed, while trio WES analysis identified a novel heterozygous [Chr18:c.1757C>T (p.Pro586Leu)] variant in the GATA6 gene. This variant was inherited from the father, who carries a clinical diagnosis of tetralogy of Fallot. These findings provide new insights into novel GATA5/6 variants, elaborate on the genotypic and phenotypic association, and highlight the critical role of GATA5 and GATA6 transcription factors in a wide spectrum of right-sided CHDs. Full article

Background: Tetralogy of Fallot (TOF) is a complex congenital heart condition characterized by four major anatomical abnormalities. Accurate preoperative imaging is critical for optimal surgical outcomes, with transthoracic echocardiography (TTE), computed tomography angiography (CTA), and conventional catheter angiography (CCA) being the primary diagnostic tools. This study aimed to compare the diagnostic utility of TTE, CTA, and CCA in preoperative evaluations of TOF patients, focusing on anatomical parameters, imaging accuracy, and patient outcomes. Methods: A retrospective, single-center analysis included TOF patients under one year of age who underwent complete repair between January 2021 and December 2024. Preoperative imaging with TTE, CTA, and CCA was analyzed for parameters including pulmonary artery diameters, Nakata index, McGoon ratio, and Z-scores. Radiation exposure, procedure duration, contrast volume, and complications were documented. Statistical analyses were performed to assess the comparative accuracy and safety of these modalities. Results: All patients underwent TTE (n = 127), while CTA was performed in 86 patients and CCA in 41 patients. Among 127 patients, 62% were male, with a mean age of 5.81 ± 2.15 months. On TTE, CTA and CCA provided statistically similar measurements of the pulmonary annulus, main pulmonary artery, and branch diameters, with no significant differences in the Nakata index and McGoon ratio. CTA had a shorter procedure duration (3.1 ± 0.58 min) and lower radiation dose (1.19 ± 0.22 mSv) compared to CCA (20.73 ± 11.12 min; 5.48 ± 1.62 mSv). CTA successfully identified major aortopulmonary collateral arteries (MAPCAs) in 10% of patients and detected additional pulmonary pathologies, such as subsegmental atelectasis in 12%. Access site complications were observed in 10% of CCA cases but were absent in CTA evaluations. Conclusions: CTA emerges as a highly effective and non-invasive alternative to CCA for preoperative assessment of TOF, offering comparable anatomical accuracy with significantly reduced procedural risks, radiation exposure, and contrast volume. Combining TTE and CTA provides comprehensive diagnostic coverage, minimizing the need for invasive procedures and enhancing surgical planning. These findings underscore the evolving role of CTA in the management of congenital heart disease, contributing to improved patient safety and outcomes. Full article

Background/Objectives: Critical congenital heart disease (CCHD) is among the major causes of global neonatal morbidity and mortality. While the incidence of CCHD appears to vary across populations, much of this variation may stem from differences in detection and reporting capabilities rather than true prevalence. In Jordan, recent data revealed a congenital cardiac disease incidence of 17.8/1000 live births, much higher than international averages. Diagnosis is largely dependent upon echocardiography, which is difficult to obtain in low-resource settings where prenatal screening modalities are limited. Screening for CCHD with pulse oximetry offers a potential method to identify patients earlier and contribute to improved outcomes. Methods: This prospective cohort study evaluated 20,482 neonates screened using pulse oximetry at Al-Bashir Hospital between January 2022 and May 2024. Demographic data, pulse oximetry measurements, and echocardiogram findings were collected during the screening process after obtaining ethical approval from the Jordanian Ministry of Health. Results: Pulse oximetry screening identified 752 neonates (3.7%) requiring further evaluation by echocardiography. An abnormality was detected in 240 neonates (31.9%), which included cardiac anomalies and pulmonary hypertension. Screening led to the identification of 138 infants with CCHD, including 80 with a previously unknown diagnosis, and an additional 247 infants with conditions requiring increased monitoring or treatment. Among those with CCHD, hypoplastic left heart syndrome and Tetralogy of Fallot were the most common conditions, 3.1%, and 2.4%, respectively. The overall false positive rate was 1.8% and was higher among those screened at less than 24 h of life compared to those screened at or after 24 h of life (2.3% [95%CI 2.1–2.6] vs. 0.8% [95%CI 0.6–1.0], p < 0.001). Conclusions: Pulse oximetry screening successfully led to the early detection of CCHD among Jordanian neonates. There was a high prevalence of CCHD compared to other reported cohorts. This highlights the importance of implementing national screening protocols to improve early diagnosis and intervention. Future studies will inform the feasibility and cost-effectiveness of national implementation in this setting. Full article

Background: Pregnant women with congenital heart disease carry a high risk of complications, especially when cardiac function is suboptimal. Increasing evidence suggests that impaired right ventricular (RV) function has a negative effect on placental function, possibly through venous congestion. We report a case series of hepatic and renal venous flow patterns in pregnant women with right ventricular dysfunction after repaired Tetralogy of Fallot (ToF), relative to those observed in normal pregnancy and preeclampsia. Methods: At 20–24 weeks pregnancy, RV function was measured by echocardiography and by cardiovascular magnetic resonance in women with repaired ToF. Combined Doppler-ECG of the hepatic and renal interlobular veins were performed in three women with asymptomatic right ventricular dysfunction. Venous impedance index and pulse transit time were measured and classified as abnormal at >75th and <25th reference percentile, respectively. Results: All three women showed dilated RV and mildly impaired RV function. Both hepatic and intrarenal Doppler flow waves were abnormal and very much resembled the patterns seen in preeclampsia. One of the three women had complications including ventricular tachycardia, intrauterine growth restriction, antenatal bleeding, emergency cesarean section and acute heart failure 2 days postpartum. Conclusions: Pregnant women with mild right ventricular dysfunction after repaired ToF show abnormal venous Doppler flow waves in the liver and kidneys, similar to those observed in preeclampsia. These findings are in line with reported observations on the association between impaired RV function, abnormal return of venous blood, venous congestion and organ dysfunction. The parallel with venous Doppler flow observations in preeclampsia suggest that the venous compartment might play an important role in the etiology of preeclampsia-induced organ dysfunction. Whether this phenomenon directly affects the uteroplacental circulation is to be assessed in future research. Full article