Search Results (55)

Background and Objectives: To evaluate pregnancy outcomes and transthoracic echocardiographic (TTE) findings during the antenatal and postpartum periods in women with repaired Tetralogy of Fallot (ToF) who delivered at Çukurova University Faculty of Medicine, Balcalı Hospital, between 2011 and 2025 and to interpret these findings in the context of the 2025 European Society of Cardiology (ESC) recommendations. Materials and Methods: This single-center retrospective cohort study undertaken between 2011 and 2025 included 11 pregnant women with surgically repaired ToF. Maternal demographic characteristics, obstetric outcomes, mode of delivery, neonatal outcomes, and antenatal TTE parameters were recorded. Cardiac measurements obtained during pregnancy were compared with postpartum TTE findings performed 3–6 months after delivery to assess pregnancy-related cardiac adaptation and recovery. Results: A total of 11 pregnancies in women with repaired ToF were analyzed. Nine pregnancies resulted in live births, while one ended in missed abortion at 9 + 2 weeks and one in intrauterine fetal demise at 34 + 2 weeks. Among live births, the mean gestational age was 36 + 2 weeks and the mean birthweight was 2865 g, with a preterm delivery rate of 55.6%. Cesarean section was performed in 70% of cases, while 30% delivered vaginally. During pregnancy, the mean left ventricular ejection fraction was 62.6%, and residual tricuspid regurgitation was the most frequently observed echocardiographic finding. Postpartum TTE evaluations indicated that echocardiographic parameters were largely stable over the observation period, with no numerical change and no clear evidence of deterioration in ventricular function or progression of valvular regurgitation. Conclusions: Despite successful surgical repair, pregnancy may still pose potential risks for women with ToF, underscoring the importance of individualized, multidisciplinary management. In this cohort, pregnancy appeared to be generally well-tolerated when care was provided in accordance with contemporary ESC recommendations. The observation of preserved ejection fraction and overall stable right ventricular function in the early postpartum period suggests that favorable maternal cardiac adaptation may be achievable in carefully selected patients. Early postpartum echocardiographic assessment may be useful for identifying functional changes and informing structured long-term follow-up strategies. Full article

Background: An unroofed coronary sinus (UCS) is a rare congenital cardiac anomaly, accounting for less than 1% of atrial septal defects and frequently associated with a persistent left superior vena cava (PLSVC). Its coexistence with Tetralogy of Fallot (TOF) is exceptionally uncommon and has been reported almost exclusively in isolated case reports. Case Presentation: We report the case of a 20-year-old woman with a history of surgically corrected TOF in infancy, who presented with progressive exertional dyspnea. Multimodality imaging, including transthoracic echocardiography and cardiac magnetic resonance imaging, revealed a large atrial-level shunt caused by a type I unroofed coronary sinus associated with a persistent left superior vena cava, leading to significant right-sided chamber dilation and pulmonary hypertension. Notably, this anomaly had not been identified at the time of the initial TOF repair. The patient underwent a successful surgical correction with interatrial compartmentation and tricuspid annuloplasty, with an uneventful postoperative course. Conclusions: This case underscores the extreme rarity of the UCS–TOF association and highlights the potential for UCSs with PLSVC to remain clinically silent for years after complex congenital heart surgery. A comprehensive reassessment of the systemic venous and atrial anatomy using advanced multimodality imaging is essential in symptomatic adults with repaired TOF, as late-presenting venous anomalies may have significant hemodynamic and clinical implications. Full article

Background: Global longitudinal strain (GLS), derived from long-axis cine images (LAX), is a sensitive marker for myocardial dysfunction and a strong predictor for clinical events and future ventricular deterioration. In patients with complex congenital heart disease (CHD) transverse-oriented cine imaging is part of the standard cardiac magnetic resonance (CMR) protocol. We aimed to study the feasibility and reproducibility of strain measurements derived from transverse-oriented cine images (Transverse Strain (TrS)) and compare them with standard GLS. Methods: We retrospectively analyzed CMR cine images from 40 patients (n = 20 Fontan, n = 20 Tetralogy of Fallot (ToF)) and 10 healthy controls. Strain analysis was performed in every subject using both the conventional GLS and the TrS approach. Results: TrS showed high intra- and interobserver reproducibility in patients with CHD (intraclass correlation coefficient (ICC) > 0.75, p < 0.05). Intermethod agreement between TrS and GLS was strong in Fontan patients and in the right ventricle (RV) of ToF patients (ICC > 0.75) but showed a positive bias for TrS in the left ventricle (LV) of ToF patients (mean difference = 5.03) and in both ventricles of healthy controls (mean difference LV = 5.36, RV = 4.01). Conclusions: TrS is feasible and reproducible and may offer a new methodological approach for strain assessment, especially in CHD patients with univentricular physiology and ToF patients. Further studies are needed to validate this new approach and perform correlations to clinical outcomes. Full article

Chronic pulmonary regurgitation (PR) after the repair of tetralogy of Fallot (TOF) and other right ventricular outflow tract (RVOT) interventions leads to progressive right ventricular (RV) dilatation, altered ventricular–ventricular interaction, and an increased risk of arrhythmia and heart failure. Pulmonary valve replacement (PVR), whether surgical or transcatheter, effectively eliminates or reduces PR and is associated with short- and mid-term improvement in RV size, symptoms, and electrocardiographic markers. However, the optimal timing of intervention remains unresolved: operating late can result in irreversible myocardial damage and arrhythmogenic substrates, whereas operating early can lead to repeated reinterventions, the impact of which on hard outcomes is uncertain. This review summarizes contemporary evidence on ventricular remodelling after PVR, focusing on cardiovascular magnetic resonance (CMR) and echocardiographic markers, and critically appraises proposed criteria for timing PVR. Classic CMR-derived thresholds (RV end-diastolic volume index [RVEDVi] 150–170 mL/m², RV end-systolic volume index [RVESVi] 80–90 mL/m²) and QRS duration cut-offs are discussed alongside emerging markers of risk, including the RV mass-to-volume ratio, diffuse myocardial fibrosis (extracellular volume fraction), strain imaging, and diastolic dysfunction. Meta-analyses show consistent reverse remodelling and symptomatic benefit after PVR, but no conclusive survival benefit has been demonstrated, and data on arrhythmic outcomes remain conflicting. Key gaps include (i) the lack of prospective randomized or carefully matched comparative studies of “early” versus “deferred” PVR; (ii) limited understanding of how myocardial fibrosis, RV hypertrophy, and diastolic dysfunction interact with volume load and timing to influence long-term outcomes; (iii) under-representation of adult and older adult TOF cohorts; and (iv) insufficient integration of multiparametric risk scores and machine-learning approaches into clinical decision-making. Future research should prioritize multicentre longitudinal cohorts with standardized imaging, electrophysiological and clinical endpoints, incorporate advanced imaging techniques (e.g., strain, 3D late gadolinium enhancement, and T1 mapping), and explore precision-medicine strategies to individualize PVR timing. Full article

Introduction: Congenital structural anomalies of the pulmonary artery in children, encompassing defects such as pulmonary atresia (PA), pulmonary stenosis (PS), pulmonary artery hypoplasia, and tetralogy of Fallot (ToF), pose significant challenges in pediatric cardiac surgery due to impaired blood flow in pulmonary circulation. Traditional options for conventional repair—including autologous materials such as the native pericardium and synthetic materials such as artificial patches—have limitations including a lack of growth potential and vulnerability to restenosis over time. ProxiCor^® patches, based on the extracellular matrix (ECM), have emerged as biologically compatible substitutes capable of fostering tissue regeneration. The primary outcomes of this study were the safety (absence of patch-related complications such as restenosis, dilation, aneurysm, infection, or thrombosis) and feasibility (intraoperative handling and surgical success) of ProxiCor^® for pulmonary artery and right ventricular outflow tract (RVOT) reconstruction in a single-center pediatric cohort. Secondary outcomes included mortality, postoperative complications (prolonged mechanical ventilation > 72 h, need for continuous renal replacement therapy (CRRT), and intensive care unit (ICU) and hospital stay), and qualitative echocardiographic assessment of vessel patency during follow-up. Patients and methods: A retrospective analysis was conducted in 25 consecutive pediatric patients who underwent pulmonary artery or RVOT reconstruction with ProxiCor^® at the Department of Pediatric Cardiac Surgery in Poznań (Poland) between the years 2023 and 2024. Surgical techniques, clinical outcomes, and follow-up data were assessed using transthoracic echocardiography (TTE). Results: The median age was 224 (Q1–Q3: 124–362) days, and median weight was 4.2 (Q1–Q3: 2.8–8.5) kg. Procedures targeted repairs of the main pulmonary artery (MPA), right pulmonary artery (RPA), left pulmonary artery (LPA), and RVOT. Diagnoses included tetralogy of Fallot (ToF), pulmonary artery stenosis (PS), pulmonary atresia (PA), pulmonary artery hypoplasia, and anomalous left coronary artery from the pulmonary artery (ALCAPA). The mortality rate stood at 8% (2/25), stemming from multiorgan failure and hemorrhagic stroke, unrelated to the patch. Over a median observation period of 483 (Q1–Q3: 363–584) days, no patch-related complications (e.g., restenosis or dilation) arose. The median hospitalization time was 22 (Q1–Q3: 8.5–38.5) days. Conclusions: ProxiCor^® ECM patches appear to be safe and feasible for use in pulmonary artery and RVOT reconstruction, with favorable early outcomes. However, the small cohort size, lack of a control group, and limited mid- to long-term echocardiographic data preclude definitive conclusions about long-term outcomes or comparative effectiveness. Full article

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, classically characterized by right ventricular outflow tract obstruction, ventricular septal defect, overriding aorta, and right ventricular hypertrophy. Recent advances in molecular and genomic research indicate that TOF is part of a phenotypic continuum encompassing Trilogy, Tetralogy, and Pentalogy of Fallot, in which the variability of anatomical presentation reflects shared genetic and epigenetic mechanisms with highly variable penetrance and expressivity. Variants in NOTCH1, FLT4, KDR, GATA6, and TBX1 highlight key pathways in conotruncal development and endothelial–mesenchymal transition, yet these well-known genes explain only a fraction of the genetic landscape. Emerging studies have identified additional candidate genes and networks involved in cardiac morphogenesis, including transcriptional regulators, signaling mediators, chromatin-remodeling factors, and splicing-associated genes such as PUF60 and DVL3. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA expression, further modulate phenotypic expressivity and contribute to variability along the Trilogy–Tetralogy–Pentalogy spectrum. This review integrates current genomic and clinical evidence to provide a comprehensive overview of the molecular architecture of Fallot-type conotruncal malformations, emphasizing the interplay between genetic and epigenetic mechanisms, genotype–phenotype correlations, and implications for diagnosis, risk stratification, counseling, and personalized management in the era of precision cardiology. Full article

Background/Objectives: Children with complex congenital heart disease (CHD) often exhibit lower levels of physical activity, but whether chronic cyanosis exposure is associated with activity participation is unclear. This cross-sectional study investigated whether the duration of cyanosis prior to surgical correction was associated with submaximal or maximal exercise tolerance or daily habitual physical activity. Methods: Thirty-six children (10–17 years) with transposition of the great arteries (TGA), tetralogy of Fallot (TOF), or Fontan physiology were tested with cardiopulmonary exercise testing (Bruce treadmill protocol) and 7 days of accelerometry. Cyanosis duration from birth to surgery was calculated. Results: Only 17% of participants were meeting daily physical activity recommendations. Age and exercise time were the strongest predictors of activity behavior. Children with <2 months of cyanosis had peak VO₂ comparable with normative data (105% predicted), while those with longer durations of exposure had reduced submaximal and peak capacity (p < 0.001). The direct effect of days exposed to cyanosis on daily physical activity was not statistically significant (p = 0.55) but the indirect effect via submaximal energy consumption was statistically significant (p = 0.05), suggesting that a longer duration of cyanosis exposure negatively impacted physical activity through its detrimental effect on submaximal exercise capacity. Conclusions: These findings suggest that children with prolonged cyanosis exposure are at higher risk for reduced submaximal exercise capacity, which has a negative impact on daily physical activity participation. Age and exercise test duration can accurately estimate daily physical activity behaviors. Interventions to support these patients require investigation due to their increased risk for morbidities associated with inactive lifestyles. Full article

Artificial intelligence (AI) is rapidly transforming cardiovascular medicine, with profound implications for congenital heart disease (CHD). Tetralogy of Fallot (ToF), the most common cyanotic disease, requires lifelong surveillance and complex management because of late complications such as pulmonary regurgitation, arrhythmias, and right ventricular dysfunction. This review synthesizes current evidence on AI applications across the continuum of ToF care—from prenatal diagnosis to adulthood follow-up. We examine advances in imaging, perioperative planning, intraoperative monitoring, intensive care, and long-term surveillance, including wearable and implantable technologies. Machine learning (ML), deep learning (DL), and natural language processing (NLP) are revolutionizing diagnostic accuracy, risk stratification, surgical decision-making, and personalized long-term care. The future lies in the integration of multimodal data, including imaging, electronic health records (EHRs), genomic information, and continuous monitoring, to support precision medicine. Challenges remain regarding dataset limitations, interpretability, regulatory standards, and ethical concerns. Nevertheless, ongoing innovation and collaboration between clinicians, engineers, and regulators promise a new era in congenital cardiology. By embedding AI throughout the patient journey, healthcare systems may improve outcomes and quality of life for individuals with ToF. Full article

Background and Clinical Significance: FLNC encodes filamin C, a muscle-scaffolding protein crucial for cardiac integrity. Pathogenic FLNC variants cause diverse cardiomyopathies (hypertrophic, dilated, restrictive, and arrhythmogenic) and myofibrillar myopathies, but their role in congenital cardiac malformations is unclear. Notably, FLNC has not been implicated in structural defects such as Tetralogy of Fallot (TOF) to date. Case Presentation: Two fetuses from the same family were prenatally diagnosed with TOF via ultrasound. The trio whole-exome sequencing of the second fetus and her parents identified a novel heterozygous truncating FLNC variant (NM_001458.5:c.1453C>T, p.Q485*). Sanger sequencing confirmed the same variant in the earlier TOF fetus. The mother carried the variant but was asymptomatic. In vitro mutagenesis in rat cardiomyocytes showed that the mutant FLNC construct produced markedly reduced FLNC proteins compared to the wild type and did not form abnormal cytoplasmic aggregates. Conclusions: We report on a novel FLNC truncating variant associated with fetal TOF, extending the spectrum of FLNC-related cardiac anomalies. The variable outcomes among variant carriers—from fetal TOF to adult cardiomyopathy or no clinical manifestations—underscore the complex genotype–phenotype correlations of filaminopathy. This case highlights the importance of comprehensive genetic evaluation in families with diverse cardiac phenotypes and suggests that additional genetic factors likely influence phenotypic expression. Full article

Background: Postoperative junctional ectopic tachycardia (JET) is a potentially life-threatening arrhythmia that may occur after congenital heart surgery, especially following tetralogy of Fallot (TOF) repair. It can cause hemodynamic instability due to atrioventricular dissociation. This study aimed to evaluate the incidence, risk factors, and outcomes of JET after TOF repair, with particular focus on management strategies and the impact of JET duration on recovery. Methods: This retrospective study included 114 pediatric patients who underwent TOF repair between 2015 and 2023. The study was approved by the institutional ethics committee (File No: 2023/09-31, Date: 10 October 2023). Postoperative JET was diagnosed based on standard electrocardiographic criteria. Perioperative variables, surgical techniques, and postoperative outcomes were analyzed. Results: JET occurred in 19 patients (16.7%). Compared with patients without JET, those with JET had higher complication rates (73.7% vs. 42.1%, p = 0.02), prolonged inotropic support, and increased mortality (15.8% vs. 2.1%, p = 0.024). Ionized calcium (p < 0.001) and pH levels (p < 0.037) were significantly lower in JET patients. Right ventricular outflow tract muscle resection was strongly associated with JET occurrence (p = 0.003). Although cardiopulmonary bypass and aortic cross-clamp times did not predict JET, both correlated with JET duration (p < 0.05). Conclusions: Postoperative JET remains a major concern following TOF repair, leading to adverse outcomes and longer recovery. Optimizing perioperative management may help reduce JET-related complications, though further multicenter prospective studies are needed to confirm these findings. Full article

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

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

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