Tetralogy Of Fallot Research Articles

Primary repair versus pulmonary artery banding in complete atrioventricular canal defects in the modern surgical era.

Primary repair versus pulmonary artery banding in complete atrioventricular canal defects in the modern surgical era.

Comparison of single-source cardiac CT and CMR quantified ventricular volumes and function in congenital heart disease.

Comparison of single-source cardiac CT and CMR quantified ventricular volumes and function in congenital heart disease.

Stenting the Ductus Arteriosus of a Patient with Tetralogy of Fallot and Trisomy 18: Case Report and Updated Review

Ductal stent implantation is a palliative procedure that can be performed in cases of congenital heart defects dependent on the patency of the ductus arteriosus, such as Tetralogy of Fallot. It is a widely effective technique, with low complication rates and less invasive than the modified Blalock-Taussig palliative surgery, making it a viable and safe option for high-surgical-risk patients. Moreover, it is crucial for the anesthesiologist to be familiar with the pathophysiological characteristics of these ductus arteriosus-dependent heart conditions to ensure appropriate perioperative management. The objective of this work is to describe the challenging anesthetic management of a newborn with Tetralogy of Fallot and Edwards Syndrome who underwent ductal stent implantation via endovascular approach at a quaternary care center.

Prognostic analysis of children with tetralogy of Fallot through a small incision in the right axilla

ObjectiveCompare the clinical efficacy of a minimally invasive small incision in the right axilla vs. traditional median sternotomy in the surgical treatment of tetralogy of Fallot (TOF).MethodsA retrospective analysis was conducted on 330 infants and young children under the age of 3 who underwent radical surgery for tetralogy of Fallot between March 2022 and March 2024. Patients were categorized into two groups based on the surgical approach. To ensure the consistency of preoperative baseline data (weight, gender, age, O2 saturation, main pulmonary artery and pulmonary branches diameter, McGoon ratio) between the two groups, the propensity score matching method was applied for 1:1 matching, resulting in two cohorts of 228 cases. The minimally invasive group (n = 114) received surgery through a small incision in the right axilla, while the median sternotomy group (n = 114) underwent surgery via median sternotomy. Clinical parameters including demographic data (weight, gender, age, O2 saturation, main pulmonary artery and pulmonary branches diameter, McGoon ratio), cardiopulmonary bypass metrics (duration of bypass, aortic cross-clamp time), duration of mechanical ventilation, intensive care unit (ICU) stay, postoperative chest drainage volume within 24 h, pulmonary valve regurgitation, and complications (reintubation, peritoneal dialysis, reoperation, extracorporeal membrane oxygenation (ECMO) use, infection, and mortality) were collected for comparison between groups.ResultsNo statistically significant differences were observed between the two groups in 24 h chest drainage volume, mortality, reintubation, reoperation, ECMO use, and infection. However, the minimally invasive group showed significantly shorter ventilator duration and ICU stay and a reduced rate of peritoneal dialysis (all p < 0.05).ConclusionIn infants and children under 3 years old with TOF, surgical correction via a right axillary small incision achieves equivalent clinical outcomes to traditional median sternotomy, without increasing postoperative mortality or complication rates. In addition, the minimally invasive approach offers benefits of reduced surgical trauma and enhanced postoperative recovery.

Overweight and Obesity in Adults with Congenital Heart Disease and Heart Failure: Real-World Evidence from the PATHFINDER-CHD Registry

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.

Electrocardiogram indicators of right ventricular dilation in repaired tetralogy of Fallot patients

ABSTRACT Background Patients with surgically repaired tetralogy of Fallot (rTOF) often develop chronic pulmonary regurgitation (PR), necessitating pulmonary valve replacement (PVR). While cardiac MRI is crucial for PVR timing, its availability is limited. This study evaluates electrocardiographic (ECG) findings – specifically the R-wave amplitude in lead V1 (V1R) and the sum of the R-wave amplitude in lead V1 and the deepest S-wave amplitude in lead V5 or V6 (V1R + V5S or V6S) – as predictors of cardiac MRI findings. Patients and methods We retrospectively analyzed 35 rTOF patients (mean age 34 ± 9 years; 60% male) who underwent cardiac MRI from 2019 to 2022, assessing correlations between ECG parameters (V1R, V1R + V5S or V6S, and QRS duration) and MRI findings (RVESVI and RVEDVI). Results V1R showed significant correlation with RVESVI (r = 0.486, p = 0.003) and was notably higher in patients with RVESVI ≥ 80 mL/m2. A V1R cutoff of 20 mm identified RVESVI ≥ 80 mL/m2 with 67% sensitivity and 77% specificity. Conclusions V1R on ECG may help predict the need for cardiac MRI, aiding in the timely PVR planning for rTOF patients.

The relationship of NOS3 G894 T (rs1799983) gene polymorphism in the risk of congenital heart disease: a meta-analysis and bioinformatics study.

Nitric Oxide Synthase 3 (NOS3) G894 T (rs1799983) is an important regulator of cardiac development. Its role in congenital heart disease (CHD) has been extensively studied in recent years, but the results are contradictory. The aim of the present study was to better elucidate the relationship between the NOS3 G894 T gene polymorphism and susceptibility of CHD and its specific subtypes. A comprehensive literature search was conducted across several databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, and Wan Fang. Meta-analysis was carried out using RevMan 5.4 software, and the odds ratio (OR) with 95% confidence intervals (CI) was used as the effect measure. Additionally, bioinformatics analysis was employed to explore the impact of NOS3 gene mutations on tetralogy of Fallot (TOF), using publicly available microarray datasets to assess NOS3 gene expression. Nine studies were included, comprising 1931 CHD cases and 1910 controls. Meta-analysis showed that the NOS3 G894 T polymorphism was associated with an increased risk of CHD in three genetic models: allele model (T vs G, OR = 1.31, 95% CI [1.02, 1.68], P = 0.04), homozygous model (TT vs GG, OR = 1.60, 95% CI [1.13, 2.26], P = 0.007), and dominant model (GT + TT vs GG, OR = 1.44, 95% CI [1.02, 2.05], P = 0.04). Subgroup analyses revealed a strong association with atrial septal defect (ASD), conotruncal defects (CTD), and septal defects, with the most significant correlation found for ASD. The NOS3 G894 T polymorphism was associated with the risk of CHD in ethnic subgroup, increasing the risk of CHD in white race. Bioinformatics analysis did not find significant differences in NOS3 gene expression between individuals with TOF. The NOS3 G894 T (rs1799983) gene polymorphism is significantly associated with the risk of CHD, with notable variations in this association across different regions and ethnic groups. The T allele increases the risk of CHD by 31% compared to the G allele. Additionally, this polymorphism is linked to specific CHD subtypes, especially ASD.

Clockwise aortic root rotation in patients with tetralogy of fallot assessed with cardiovascular magnetic resonance imaging.

Rotation of the aortic root (AoR) has previously been observed in children with Tetralogy of Fallot (TOF) using 2-dimensional echocardiography. The present study uses cardiovascular magnetic resonance (CMR) imaging to assess whether a clockwise AoR rotation is a common feature in adults with TOF. AoR rotation was measured in the CMR images of consecutive adult patients with corrected TOF and controls. The AoR rotation was assessed in the parasternal short-axis view by measuring the angle of the non-coronary sinus (angle NCS) relative to the interatrial septum (IAS). The angle between IAS and posterior atrial wall was measured to asses IAS reliability as a key anatomical landmark. Inter-observer agreement was determined using intra-class correlation coefficients (ICC). A total of 25 adults with TOF (mean age:33.2 ± 13.1 years;52% male) and 30 controls (mean age:54.5 ± 19.0 years;50% male) were assessed. The angle NCS was greater in TOF patients than in controls (46.2 ± 17.1⁰vs.23.4 ± 15.0⁰, p < 0.001), reflecting a clockwise AoR rotation. As expected, between TOF patients and controls there was no significant difference in the angle IAS (81.1 ± 8.4⁰vs.78.4 ± 9.5⁰, p = 0.46). Inter-observer reliability of CMR measurements was good for the clinically important angle NCS (ICC 0.77, 95%-CI:0.63-0.86) and moderate for the angle IAS (ICC 0.68, 95%-CI:0.51-0.80). This is the first study to demonstrate with CMR that a clockwise rotation of the AoR is a common feature in patients with TOF. This clinical investigation shows the value of CMR for the assessment of the spatial AoR position in adult patients with congenital heart disease.

Reinterventions and medical costs after tetralogy of Fallot repair: a retrospective cohort study using health insurance claims in Japan.

Reinterventions after congenital heart disease surgery include not only reoperations but also medical catheter interventions, and the details of these treatment realities are often unclear. This study aimed to elucidate the medical and surgical reinterventions and associated medical costs after the tetralogy of Fallot (TOF) repair using Japanese health insurance claims data. We analyzed reinterventions and medical costs from insurance claims data of patients who underwent TOF repair between 2005 and 2021. Of 174 patients who underwent TOF repair, 23 (13.2%) received a total of 34 reinterventions. These included 23 percutaneous catheter interventions and 11 reoperations. The 5-year reintervention-free rate was 87.5% overall, 94.9% for surgeries with right ventricular outflow tract reconstruction (N = 130), and 65.6% for surgeries with peripheral pulmonary artery plasty (N = 44). The median (interquartile range) medical cost for patients without reintervention was ¥5.33 million (4.62-7.14 million) and the cost for the patients with reintervention was ¥ 10.59 million (7.73-13.97 million). Using Japanese insurance claims data, we analyzed the reoperation and catheter intervention after the TOF repair. The reintervention-free rate after TOF repair differed significantly by surgical procedure with a tendency for poorer postoperative prognosis, particularly in cases involving the peripheral pulmonary artery plasty. These analysis results may contribute to predicting outcomes after TOF repair for healthcare professionals.

Mid-Term Longitudinal Assessment of Ventricular Function after Transcatheter Pulmonary Valve Replacement in Tetralogy of Fallot with or without Pulmonary Atresia.

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Patients who undergo surgical repair for TOF or TOF with pulmonary atresia (PA) may develop chronic severe pulmonary regurgitation (PR), which leads to right ventricle (RV) dilation and dysfunction. Pulmonary valve replacement is performed to restore pulmonary valve function and reverse the RV remodeling. Traditionally, pulmonary valve replacement has been performed surgically, but over the past two decades, transcatheter pulmonary valve replacement (TPVR) has emerged as an alternative approach. However, the optimal timing for TPVR remains a clinical challenge and a highly debated topic. Our study's primary aim is to evaluate the mid-term effect of TPVR on biventricular systolic function in patients with long-standing PR post-repair of TOF or TOF with PA. This retrospective single-center study included 30 patients with repaired TOF or TOF/PA who underwent first-time TPVR between 2012 and 2022. Echocardiographic assessments of right ventricular (RV) and left ventricular (LV) function were conducted at baseline and up to 3-5years post-TPVR. Key parameters included RV fractional area change (FAC), RV strain, RV dP/dt, LV ejection fraction (EF), and LV longitudinal strain (LVLS). Statistical comparisons were made between pre- and post-TPVR time points. At baseline, most patients showed reduced RV and LV systolic function. Following TPVR, RV function did not show significant improvement on follow-up. However, LV longitudinal strain gradually improved over time and reached statistical significance at long-term follow-up (p = 0.004). LV EF showed an upward trend but did not reach significance. biventricular systolic function is decreased in many patients with repaired TOF or TOF/PA and long-standing severe PR. Transcatheter pulmonary valve replacement in this cohort resulted in improved LV strain but no improvement in RV function on mid-term follow up. These findings suggest the need to reconsider the timing of TPVR. Future studies should investigate whether earlier valve replacement could lead to better outcome of ventricular function in this patient population.

De Novo Missense Variant in Bovine WDR33 Associated With a Complex Syndromic Form of Cleft Palate With Pentalogy of Fallot and Internal Hydrocephalus

ABSTRACTBackgroundCleft palate (CP) is a congenital defect characterized by an opening in the palate. Two crossbred paternal half‐sibs with a complex syndrome including CP were identified.Hypothesis/ObjectivesCharacterize disease phenotype and evaluate the genetic cause of the observed syndrome.AnimalsTwo affected calves, their parents, and 5576 control cattle genomes.MethodsThe affected animals were evaluated clinicopathologically. Paternal half‐sibling trio‐based whole genome sequencing (WGS) was performed using genomic DNA extracted from the blood of the two affected calves and both dams, and sperm of the common sire.ResultsThe cases were presented with a CP Veau II, permanent recumbency, strabismus, tachycardia, and tachypnea. Echocardiographic findings were consistent with tetralogy of Fallot associated with patent foramen ovale (pentalogy of Fallot). Necropsy examination identified hydrocephalus in addition to CP and confirmed the clinical diagnosis of pentalogy of Fallot. The calves were diagnosed with a complex syndromic form of CP with pentalogy of Fallot and hydrocephalus. Analysis of the breeding data showed that 19/45 recorded offspring of the sire were not viable. Genetic analysis identified a missense variant in WDR33 that was heterozygous in both analyzed cases and in an estimated 40% of the paternal gametes of the mosaic founder, but absent in both dams and controls.Conclusions and Clinical ImportanceThis study alerts veterinarians and breeders to the potential occurrence of dominant de novo mutations in cattle and emphasizes that, in herds using a natural service sire, the consequences of an asymptomatic germline mosaic can be important.

Tetralogy of Fallot with Absent Pulmonary Valve Syndrome: A Case Series

Tetralogy of Fallot (TOF) with absent pulmonary valve syndrome (APVS) is an extremely rare variant of TOF, with a ratio of 3-6%. Significant pulmonary insufficiency due to this valvular absence promotes dilation of the pulmonary arteries, and this can lead to airway compression during intrauterine life and after birth. The degree of compression is relative to the degree of hypoplasia of the respiratory tract. The severity of the respiratory problems indicates high mortality rates. This study aimed to present the short and mid-term outcomes following surgical repair of three TOF-APVS patients. One patient also had associated Townes-Brock Syndrome, which is extremely rare by itself. On follow-up, one patient could not be separated from cardiopulmonary bypass (CPB), and she was placed on arterio-venous extracorporeal membrane oxygenator (A-V ECMO) support before she died on the 5th day post-operatively. The patient with Townes-Brock syndrome died post-operatively 3.5th months due to pulmonary complications.

Frequency and Patterns of Congenital Heart Defects in Neonates of Diabetic Mothers at a Tertiary Care Hospital

Objective: To assess the incidence and spectrum of Congenital Heart Defects (CHDs) in neonates born to mothers with Gestational Diabetes Mellitus (GDM), compared to those born to non-diabetic mothers. Methodology: This retrospective comparative study was conducted at the Department of Pediatric Cardiology, Bahawal Victoria Hospital, Bahawalpur, over one year from September 2023 to September 2024. A total of 260 neonates were included and divided into two groups: 130 born to mothers with GDM and 130 to non-diabetic mothers. Inclusion required complete maternal antenatal and neonatal records. Neonates with syndromic features or known chromosomal anomalies were excluded. Maternal glycemic status was verified from antenatal clinic files, and CHD diagnosis was based on echocardiography performed within the first week of life. The frequency and types of CHDs were recorded and compared. Data were analyzed using SPSS version 26.0, with p &lt; 0.05 considered statistically significant. Results: CHDs were significantly more common among neonates of diabetic mothers (15.4%) compared to non-diabetic mothers (4.6%) (p &lt; 0.01). Patent foramen ovale (PFO) and atrial septal defect (ASD) were significantly higher in the diabetic group—10% vs. 3.1% and 11.5% vs. 3.8%, respectively. Although not statistically significant, increased frequencies of ventricular septal defect (VSD), patent ductus arteriosus (PDA), dextro-transposition of the great arteries (dTGA), and tetralogy of Fallot (TOF) were also noted in neonates of diabetic mothers. Conclusion:Neonates born to mothers with GDM are at a significantly higher risk of developing congenital heart defects, emphasizing the need for early fetal cardiac evaluation and targeted postnatal screening in this high-risk group.

Evaluation of Pulmonary Regurgitation in Pediatric Patients with Operated Tetralogy of Fallot Using Automated Right Ventricle Software

Objective: In this study, we aimed to evaluate right ventricular (RV) functions using four-dimensional echocardiography and an automated RV software in patients with residual pulmonary regurgitation following surgical repair of Tetralogy of Fallot. Methods: We evaluated 18 patients with pulmonary regurgitation after Tetralogy of Fallot repair. The Tomtec V2.0 software program was used for automated right ventricle assessment. The results were compared with those of an 11-person control group. The measurements of both groups were analyzed. Results: The mean age of the patient group was 11.3 ± 3.4 years, while that of the control group was 11.3 ± 2.9 years (p &gt; 0.05). RV end-diastolic volume (EDV) was found to be higher in the patient group compared to the controls (116.6 ± 47.3 vs. 54.3 ± 23.4 ml, p &lt; 0.001). The rate of age-related increase in RV EDV was also higher in the patient group. A strong positive correlation was found between RV EDV and age (p &lt; 0.001). Conclusion: The use of Tomtec V2.0 automatic contour detection is a practical method for assessing RV function in patients who have undergone surgical correction of Tetralogy of Fallot. It can also be employed to determine whether patients meet the criteria for pulmonary valve replacement. The degree and consequences of RV dilation depend on the patient’s age and may be influenced by other factors.

Valve-preserving technique for tetralogy of fallot by transannular delamination.

BackgroundValve-sparing repair for tetralogy of Fallot is challenging in patients with hypoplastic pulmonary valves. Recently, we adopted transannular incision and delamination. This study evaluates its feasibility for right ventricular outflow relief, valve function, and growth.MethodsWe retrospectively reviewed records of patients with tetralogy of Fallot or Fallot-type double-outlet right ventricle who underwent intracardiac repair from October 2013 to December 2020.ResultsTwenty-six patients were enrolled. Two patients who underwent the Rastelli procedure were excluded, leaving 24 for evaluation. Eleven underwent valve-sparing repair, eight underwent valve-preserving repair with transannular delamination, and five underwent the transannular patch procedure. The median age and weight at surgery were 11.7 months (1.9-40.2 months) and 7.6 kg (3.7-12.7 kg). No patients died or required reintervention for pulmonary valve stenosis or regurgitation during a median follow-up of 42.5 months (4.6-72.1 months). In the delamination group, the mean preoperative pulmonary valve z-score was -2.1 ± 1.0, improving significantly to 0.2 ± 0.8. Pulmonary regurgitation was mild in six of eight patients, while two with the smallest preoperative annulus developed moderate regurgitation. Despite no significant difference in the preoperative pulmonary valve annulus between the delamination and transannular patch groups, the delamination group had significantly lower postoperative pulmonary valve regurgitation, while no significant difference in stenosis.ConclusionsValve-preserving repair using the transannular delamination technique is feasible in patients with tetralogy of Fallot, reducing pulmonary regurgitation and avoiding transannular patch use. Long-term data with more patients are required to show the utility of this approach.

Quantitative comparisons of pulmonary artery hemodynamics before and after Pulsta valve implantation in patients with Tetralogy of Fallot using computational fluid dynamics

Background and objectivesThe evaluation of percutaneous pulmonary valve implantation (PPVI) performance has been predominantly confined to assessing changes in the right ventricular volume using magnetic resonance imaging (MRI). This study aimed to evaluate the hemodynamic changes in the pulmonary arteries following PPVI using computational fluid dynamics (CFD) in patients with Tetralogy of Fallot.MethodsWe conducted CFD analysis based on MRI scans performed before and after PPVI using Pulsta valve in nine patients who underwent PPVI between 2016 and 2021. Statistical analysis, including Wilcoxon rank-sum tests and multivariable linear regression, was performed to examine the associations between CFD data and non-CFD factors, as well as changes in these parameters after PPVI.ResultsBefore PPVI, forward and backward flow velocities in the right pulmonary artery (RPA) were higher than those in the left pulmonary artery (LPA) and main pulmonary artery (MPA) (forward: MPA/RPA/LPA = 19.9/32.7/19.3 cm/s, backward: MPA/RPA/LPA = 10.1/17.0/9.1 cm/s). After PPVI, velocities decreased (forward: MPA/RPA/LPA = 13.3/14.2/8.3 cm/s, backward: MPA/RPA/LPA = 2.3/2.6/1.7 cm/s), reducing the differences among PAs. After PPVI, the vorticity (RPA; 3.9–1.6/s, p = 0.008, LPA; 4.4–1.8/s, p = 0.011, MPA; 5.4–1.5/s, p = 0.008), and energy dissipation (104.1–38.1 mW, p = 0.028) decreased significantly, whereas changes in the Womersley and Reynolds numbers were not statistically significant. There was no correlation between the right ventricular end-diastolic volume index and energy dissipation, and the changes in each of them were also unrelated to each other.ConclusionA deeper understanding of the hemodynamics of pulmonary arteries using CFD can aid in evaluating the effectiveness of PPVI and refining its indications in patients with Tetralogy of Fallot.

A novel heterozygous pathogenic variant in HEY2 led to a familial form of non-syndromic Tetralogy of Fallot.

Tetralogy of Fallot (TOF) aetiologies remain largely unknown. Although syndromes with genetic cause have been involved, non-syndromic TOF are not completely elucidated, with a genetic diagnosis in less than 20% of the cases. HEY2 is a basic helix-loop-helix (bHLH) repressive transcription factor implicated in cardiac development. In this study, we identify a novel heterozygous missense variant in HEY2 gene segregating within a family presenting with non-syndromic TOF with autosomal dominant transmission. The identified variation c.171 G > C p.(Glu57Asp) was tested through gene reporter assay, revealing a complete disruption of HEY2 repressive activity. These results suggest that HEY2 is a novel gene implicated in the pathogenesis of Tetralogy of Fallot, expanding the genetic spectrum of this congenital heart defect and reinforcing the role of monogenic contributions in non-syndromic TOF.

Prognostic value of neutrophil-lymphocyte ratio, absolute lymphocyte count, and thrombocyte-lymphocyte ratio in predicting the outcomes of tetralogy of fallot primary repair.

Tetralogy of Fallot (ToF) is a chronic hypoxic condition that increases the risk of inflammatory responses during surgery. However, many inflammatory biomarkers used to predict surgical outcomes are costly and not widely accessible. This single-center, retrospective observational study aimed to compare the prognostic value of neutrophil-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and thrombocyte-lymphocyte ratio (TLR) in predicting outcomes of ToF primary repair. Between January 2020 and December 2022, 501 patients underwent ToF primary repair. Our findings revealed low postoperative reoperation (6.5%) and 30-day mortality (4.7%) rates, but prolonged LOS (92.2%) and a high complication rate (84%), with grade IVa (27.9%) and grade I (26.4%) complications being the most common. Elevated NLR (r = 0.132, p = 0.014), female gender (r = 0.117, p = 0.027), associated diagnoses (r = 0.104, p = 0.047), and prolonged surgical duration (r = 0.176, p = 0.001) were linked to higher complication burdens, though the correlations were weak. Among the three indexes, preoperative NLR demonstrated the strongest predictive value for complications, despite its low sensitivity and specificity. Given its accessibility and cost-effectiveness, NLR may serve as a useful tool for identifying high-risk patients and improving postoperative monitoring. Future multicenter prospective studies are necessary to validate the prognostic value of preoperative NLR under standardized conditions, across a broader patient population, and with more comprehensive confounding variables adjustments, ultimately improving ToF surgical outcomes (Clinical Trial NCT05976204).

Wnt11 Positively Regulates Neonatal Cardiomyocyte Maturation at the Interphase of Life via Frizzled 4 Receptor.

Congenital heart defects (CHDs) affect 1% of live births and remain the leading cause of infant morbidity and early mortality. While most studies focus on the genetic basis of CHDs, relatively little is known about the interplay between intrinsic signaling and external environmental factors in the progression of CHDs after birth during the perinatal circulatory transition window when environmental stress factors are prevalent. We recently explored such interplay through a newly identified gene-environment regulatory circuit involving Wnt11 signaling and systemic hypoxia. Specifically, we demonstrated that activation of the Wnt11/Rb1 axis is critical for normal chamber-specific development after birth. This regulatory switch is disrupted by systemic hypoxia more robustly in the right ventricle (RV) than the left ventricle (LV), leading to enhanced neonatal cardiomyocyte cell cycle activity in an RV-specific manner, resulting in delayed maturation and attenuation of ventricular patterning in response to systemic hypoxia stress in the neonatal heart. Furthermore, we found that the Wnt11/Rb1 axis is also inactivated in infantile hearts with cyanotic CHDs, such as tetralogy of Fallot (TOF), potentially contributing to hypoxia-associated RV abnormalities in this context. However, the molecular players of this signaling cascade in neonatal cardiomyocyte remain largely unknown. Herein, we report that Frizzled 4 (Fzd4) acts as a specific upstream receptor for Wnt11 in neonatal cardiomyocytes. Specifically, Fzd4 exhibited an expression pattern like Wnt11 in neonatal heart perinatal circulatory transition under normal and hypoxemic environments. Furthermore, Fzd4 loss in neonatal cardiomyocytes stimulated cardiomyocyte cell cycle activity and disrupted the Wnt11-Rb1 signaling axis mirroring the impact of the Wnt11-deficient cardiomyocyte phenotype. Finally, co-immunoprecipitation analysis confirmed the Wnt11-Fzd4 binding in isolated neonatal cardiomyocytes and intact hearts. These results demonstrate that Fzd4 is a specific and required upstream receptor for the Wnt11-Rb1 signaling activity in the neonatal heart and provides mechanistic insights into the essential role of Wnt11 as a key positive regulator of neonatal cardiomyocyte transition from proliferative to mature phenotype at the interphase of life.

Symptomatic Neonates With Tetralogy of Fallot: Shunt or Primary Repair?

Symptomatic Neonates With Tetralogy of Fallot: Shunt or Primary Repair?