Search Results (123)

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: Assessing right ventricular (RV) diastolic function by echocardiography in pediatric patients remains complex, particularly in congenital heart disease (CHD) characterized by RV pressure overload. The geometric peculiarities of the RV, respiratory influences, and age-dependent maturational changes complicate interpretation of Doppler-derived indices. This study aimed to characterize tricuspid valve (TV) pulsed-wave Doppler E/A inflow patterns in infants with CHD and RV pressure overload, evaluated shortly after surgical or percutaneous intervention. Methods: Echocardiographic analysis included TV E- and A-wave velocities obtained by pulsed-wave Doppler and measurement of E-wave deceleration time (EDT). Beat-to-beat variability was quantified over three consecutive cardiac cycles. Data were compared with a large cohort of age-matched healthy children. Results: Fifty-seven infants with CHD (35 pulmonary stenosis; 22 tetralogy of Fallot), examined 12–48 h post-intervention, were compared with 134 healthy controls. CHD patients showed markedly reduced beat-to-beat variability of both E- and A-wave velocities (p < 0.001 and p = 0.007, respectively). A three-beat E/A inversion pattern—common in neonates but variable in healthy infants—was consistently observed in CHD patients (p < 0.001). A-wave velocities were significantly higher (p < 0.001), whereas E/A ratios (p < 0.001) and EDT values (p = 0.010) were significantly lower compared with controls. Conclusions: Infants with CHD and RV pressure overload exhibit a characteristic Doppler pattern consisting of E/A ratio inversion, reduced beat-to-beat variability, increased A-wave velocity, and shortened E/A ratio and EDT. These findings may serve as practical and reproducible indicators of RV diastolic dysfunction in the early post-intervention period in neonates and infants. 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

Background: In cardiology, vasoregulation is one of the most important targets of pharmacotherapy. SOMNOtouch™-NIBP (SOMNOmedics AG, Randersacker, Germany) is a cuffless device designed for continuous, non-invasive blood pressure measurements, and it appears to be ready for use in infants and children with congenital heart disease. For infants, minor methodological modifications are required due to their small body size. Methods: Using this device, we demonstrate fluctuations in diastolic blood pressure in three patients: an infant with hypoplastic left heart syndrome after Norwood stage 1 and 2 operations; an infant with Tetralogy of Fallot with heart failure due to pulmonary overcirculation after an aorto-pulmonary shunt implantation; and a 13-year-old girl with chronic cyanosis due to a congenitally corrected transposition of the great arteries (ccTGA) with a ventricular septal defect and pulmonary stenosis. The measurement procedures are completely non-invasive and feasible in an outpatient setting. Results: The results demonstrate strong correlations between blood pressure and oxygen saturation levels as well as heart rate variability. We discuss our results in relation to current concepts of hypoxic pulmonary/systemic vasoconstriction and hypoxemia-related pathways. Conclusions: The cuffless device for continuous, non-invasive blood pressure measurement seems to be useful for infants with and without congenital heart defects who receive pharmacotherapies that modulate vasoregulation. These patients should also be non-invasively monitored for safety reasons and for a better understanding of their pathophysiology. 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: Advances in diagnosis and treatment have led to a growing population of adults with congenital heart disease (ACHD). Despite increasing life expectancy, their clinical needs—especially in older age—remain poorly defined. Cardiac and non-cardiac comorbidities are prevalent, and emerging evidence suggests accelerated biological aging compared to the general population. However, data on older patients and geriatric patients with CHD are limited. Objectives: This study aimed to characterize patients with CHD aged ≥50 years, focusing on functional status, comorbidities, sex-specific differences, and therapeutic patterns. Methods: The PATHFINDER-CHD Registry is a prospective, observational, multicenter registry enrolling patients with CHD with manifest heart failure (HF), HF history, or high HF risk. Data include anatomy, prior treatments, comorbidities, and medication use. Results: Among 1935 patients, 297 were ≥50 years old. Most had acyanotic CHD (62%); Tetralogy of Fallot (21%) was the most frequent diagnosis. A morphologic right systemic ventricle was present in 12%, and 5% had univentricular hearts. HF was manifest in 21%; 44% were classified as ACC/AHA stage B, 51% as stage C, yet 77% were in Perloff class I/II. Common cardiovascular comorbidities included aortopathy (55%), hypertension (37%), and arrhythmia (33%). Non-cardiac comorbidities included thyroid dysfunction (25%), renal impairment (18%), and neurological disease (13%). Sex-specific differences were observed. Despite HF burden, SGLT2 inhibitors and ARNIs were used in only 17% and 8.4%, respectively. Conclusions: Older patients with CHD represent a clinically complex cohort with high comorbidity burden. The findings support the concept of accelerated aging and emphasize the need for tailored interdisciplinary care strategies. Full article

Background and Clinical Significance: VACTERL association is a rare spectrum of congenital malformations that may involve the genitourinary system. We describe a challenging case of hypotonic, hyporeflexic, large-capacity bladder with bilateral obstructive megaureter in a boy with VACTERL syndrome, highlighting diagnostic and therapeutic challenges. Case Presentation: A 16-year-old boy with VACTERL syndrome, previously operated for esophageal atresia, Fallot’s tetralogy, Y-type urethral duplication, and bilateral vesicoureteral reflux, presented with breakthrough urinary tract infections, orchiepididymitis, and flank pain. Investigations revealed an enlarged bladder capacity (1000 mL), detrusor underactivity, high post-void residual volume, and bilateral hydronephrosis with megaureter. Obstruction of the bladder neck and neurological causes were excluded. After multidisciplinary discussion, bilateral ureteral reimplantation and limited reductive cystoplasty were performed. Histology revealed granulomatous foreign-body reaction due to previous bulking agent injection. Postoperative course was uneventful. At the three-year follow-up, the patient is asymptomatic with normal voiding and preserved renal function. Conclusions: This case illustrates the diagnostic and therapeutic challenges of managing late urological complications in a VACTERL patient with pre-existing urinary anomalies. The overlap of congenital and iatrogenic factors made the diagnostic pathway complex, requiring careful exclusion of neurogenic and mechanical causes. A tailored surgical strategy restored bladder function and preserved renal outcome. 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

Congenital genetic heart defects are major contributors to pediatric morbidity and mortality, underscoring the importance of early detection and individualized therapeutic strategies. This review aimed to summarize current knowledge on a spectrum of inherited cardiovascular disorders, with a focus on their genetic etiology, molecular pathogenesis, and phenotypic presentation in children. Conditions discussed include Marfan syndrome, Noonan syndrome, various cardiomyopathies, Duchenne muscular dystrophy, DiGeorge syndrome, and the tetralogy of Fallot. These six conditions were selected to represent the spectrum of pediatric cardiovascular genetic diseases, encompassing connective tissue disorders, multisystem syndromes, primary myocardial diseases, neuromuscular cardiac involvement, and structural congenital defects, thereby illustrating how distinct genotypes lead to diverse phenotypes. For each disorder, the underlying genetic mutations, associated molecular pathways, cardiovascular involvement, clinical features, and approaches to diagnosis and management are examined. Emphasis is placed on the role of timely diagnosis, genetic counseling, and personalized treatment in improving patient outcomes. The review concludes by highlighting emerging research directions and novel therapeutic interventions aimed at enhancing care for these complex pediatric conditions. 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

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