Characterization of an induced pluripotent stem cell line (NCHi013-A) from a 5-year-old male with pulmonary atresia with intact ventricular septum and a biventricular repair.

Pulmonary atresia with intact ventricular septum (PA/IVS) is a rare congenital heart defect that causes a significant decrease of blood outflow from the heart and is fatal if left untreated. iPSC line NCHi013-A was produced from peripheral blood mononuclear cells from a male child with PA/IVS using Sendai virus reprogramming. NCHi013-A displayed normal stem cell morphology, expressed markers for pluripotency, and presented ability to differentiate into cells of endoderm, ectoderm, and mesoderm lineages. The iPSC line also maintained normal karyotype, was validated for cell identity, and tested negative for transgenes and mycoplasma contamination.

Generation of an induced pluripotent stem cell line (NCHi016-A) from a 5-year-old female with pulmonary atresia with intact ventricular septum and one-and-half ventricle palliation.

Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare congenital heart defect characterized by underdeveloped pulmonary valve and right ventricular hypoplasia. Neonates undergoing surgery to open pulmonary valve have a range of post-surgical ventricular recovery: single-ventricle (1v) palliation, one-and-half ventricle (1.5v) palliation, and bi-ventricular (2v) repair. PA-IVS-1.5v typically requires surgical intervention to install cavopulmonary shunt and entails partial right ventricle recovery. NCHi016-A is an iPSC line derived from a 5-year-old female with PA-IVS-1.5v using Sendai Virus reprogramming. This iPSC line shows typical iPSC morphology, has normal karyotype, expresses pluripotency markers, and has potential to differentiate into three germ layers.

Clinical Presentation and Therapy of Truncus Arteriosus.

Truncus arteriosus (TA, also known as common arterial trunk) consists of only one great artery ("the truncus") with a semilunar valve (truncus valve) arising from the heart and an additional ventricular septal defect and (Fig. 50.1). This great artery is positioned above the ventricular septal defect and gives rise to the coronary arteries, the pulmonary arteries, and the aortic arch. Historically, TA has been classified by Collet and Edwards in three types, where in type I there was a common pulmonary artery truncus, in type II the left and right PA arise separately but close to each other, in type III both PA arise independently; in addition, there was a type IV that was later characterized as pulmonary atresia with VSD and major aortopulmonary collateral arteries arising from the descending aorta.

Current Understanding of Indications, Technical Aspects and Outcomes of Fetal Cardiac Interventions.

With the improvement in the detection of congenital heart disease in fetal life, fetal cardiac interventions are pushing the envelope in hopes of either altering the natural history of disease or improving survival in certain high-risk lesions. These interventions include fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome, fetal atrial septoplasty with or without atrial septal stenting for hypoplastic left heart syndrome and variants with intact or severely restrictive atrial septum, and fetal pulmonary valvuloplasty for severe pulmonary stenosis or pulmonary atresia with intact ventricular septum. This review discusses their indications, technical aspects, and outcomes based on available literature.

Association of right aortic arch and agenesis of ductus arteriosus in prenatal tetralogy of Fallot spectrum and its clinical implications.

OBJECTIVE: In our center, we observed an increased frequency of right aortic arch (RAA) with an agenesis of the ductus arteriosus (ADA) in prenatally diagnosed tetralogy of Fallot (ToF) and its variations. This study aimed to determine whether there is an association of RAA and ADA in fetuses with ToF. Distribution of genetic anomalies and impact on postnatal outcome were further evaluated. METHOD: Single-center retrospective observational study including pregnancies with prenatal diagnosis of ToF from 2010 to 2023. All cases were subdivided into ToF with pulmonary stenosis (PS) and pulmonary atresia (PA). Clinical and echocardiographic databases were reviewed for pregnancy outcome, genetic anomalies, and postnatal course. RESULTS: The cohort included 169 cases, 124 (73.4%) with ToF/PS and 45(26.6%) with ToF/PA. Agenesis of the ductus arteriosus was significantly associated with RAA in both subtypes of ToF (p = 0.001) compared to left aortic arch and found in 82.5% (33/40) versus 10.7% (9/84) of fetuses with ToF/PS and in 57.1% (8/14) versus 12.9% (4/31) of fetuses with ToF/PA. In both ToF/PS and ToF/PA, RAA/ADA versus RAA/patent DA revealed a significantly higher risk for the presence of genetic abnormalities, especially microdeletion 22q11.2, major aorto-pulmonary collateral arteries and a shorter time to complete surgical repair. CONCLUSION: We demonstrated a significantly increased frequency of RAA/ADA in patients with prenatally diagnosed ToF. Although this association revealed no significant impact on overall survival, the prenatal detection of RAA/ADA has implications for counseling, genetic evaluation and postnatal management.

Huge congenital right ventricular diverticulum in tetralogy of Fallot with pulmonary atresia: A double trouble.

Congenital diverticulum is an uncommonly detected cardiac lesion, especially in infancy. However, its association with cyanotic congenital heart disease is extremely rare. In the current work, we report a case diagnosed in the neonatal period with tetralogy of Fallot and pulmonary valve atresia associated with a large congenital diverticulum originating from the right ventricle.

Brugada Syndrome and Pulmonary Atresia with Intact Interventricular Septum: Fortuitous Finding or New Genetic Connection?

Brugada syndrome is a rare arrhythmogenic syndrome associated mainly with pathogenic variants in the SCN5A gene. Right ventricle outflow tract fibrosis has been reported in some cases of patients diagnosed with Brugada syndrome. Pulmonary atresia with an intact ventricular septum is characterized by the lack of a functional pulmonary valve, due to the underdevelopment of the right ventricle outflow tract. We report, for the first time, a 4-year-old boy with pulmonary atresia with an intact ventricular septum who harbored a pathogenic de novo variant in SCN5A, and the ajmaline test unmasked a type-1 Brugada pattern. We suggest that deleterious variants in the SCN5A gene could be implicated in pulmonary atresia with an intact ventricular septum embryogenesis, leading to overlapping phenotypes.

Congenital cytomegalovirus infection in a preterm infant with 22q11.2 deletion syndrome and immunological abnormalities.

The 22q11.2 deletion syndrome has many complications; one of them is immunodeficiency. However, the time of onset and the degree of immunodeficiency can vary. We report a case of a preterm infant with congenital cytomegalovirus infection complicated with 22q11.2 deletion syndrome and immunological abnormalities. Ultrasonography revealed pulmonary atresia, ventricular septal defect, major aortopulmonary collateral artery, and thymic hypoplasia. His serum chemistry tests on admission revealed immunoglobulin G, A, and M levels of 1,547 mg/dL, 70 mg/dL, and 274 mg/dL, respectively. A surface antigen analysis of the peripheral lymphocytes using flow cytometry revealed the following: relatively low CD4-positive T-cell levels (18.1%; 1,767/µL), very high CD8-positive T-cell levels (58.9%; 5,751/µL), and CD4/CD8 ratio of 0.31. The level of T-cell receptor excision circles was relatively low at 17.5 copies/µL. After birth, the CD8-positive T-cell level began to gradually decrease, whereas the CD4/CD8 ratio began to increase. Thrombocytopenia, neutropenia, and skin petechiae were observed on admission. However, the condition improved. Treatment for congenital cytomegalovirus infection was not provided due to the absence of viremia. Unfortunately, the patient died suddenly on the 158th day of life, and the cause of death was unknown. To the best of our knowledge, no association between 22q11 deletion syndrome and cCMV has been described in the recent medical literature. According to the calculation, around one newborn infant who have both 22q11 deletion syndrome and cCMV infection will be born each year in Japan. Healthcare providers should pay more attention to this medical situation in the future.

A rare case of a neonate with fallot-type absent pulmonary valve and occlusion of the left main bronchus.

Fallot-type absent pulmonary valve is a rare and complex congenital heart disease. Repair surgery for this condition during the neonatal period has a mortality rate of over 50%. We reported a neonate with Fallot-type absent pulmonary valve and occlusion of the left main bronchus. The patient's pulmonary artery had unusual anatomy of a type that has not previously been reported. This case report outlines a successful treatment strategy for patients with complex congenital heart disease and airway occlusion during the neonatal period and the effect of these unusual anatomical conditions on postoperative outcomes.

Double-chambered right ventricle in a patient with pulmonary atresia and ventricular septal defect.

Double-chambered right ventricle is a rare form of right ventricular outflow tract obstruction caused by anomalous hypertrophy of muscle bundles in right ventricle. Cases most often occur in children and rarely in adults. Most cases (80-90%) are associated with ventricular septal defect. We describe a case of pulmonary atresia and ventricular septal defect with double-chambered right ventricle. The interesting clinical findings, ECG, echocardiography and angiocardiography features are described here.

Development of Novel Sutureless Balloon Expandable Fetal Heart Valve Device Using Absorbable Polycaprolactone Leaflets.

Congenital heart disease (CHD) accounts for nearly one-third of all congenital defects, and patients often require repeated heart valve replacements throughout their lives, due to failed surgical repairs and lack of durability of bioprosthetic valve implants. This objective of this study is to develop and in vitro test a fetal transcatheter pulmonary valve replacement (FTPVR) using sutureless techniques to attach leaflets, as an option to correct congenital defects such as pulmonary atresia with intact ventricular septum (PA/IVS), in utero. A balloon expandable design was analyzed using computational simulations to identify areas of failure. Five manufactured valves were assembled using the unique sutureless approach and tested in the fetal right heart simulator (FRHS) to evaluate hemodynamic characteristics. Computational simulations showed that the commissural loads on the leaflet material were significantly reduced by changing the attachment techniques. Hemodynamic analysis showed an effective orifice area of 0.08 cm2, a mean transvalvular pressure gradient of 7.52 mmHg, and a regurgitation fraction of 8.42%, calculated over 100 consecutive cardiac cycles. In conclusion, the FTPVR exhibited good hemodynamic characteristics, and studies with biodegradable stent materials are underway.

Tricuspid Atresia with Absent Pulmonary Valve with Nearly Discontinuous Branch Pulmonary Arteries.

Absent pulmonary valve with tricuspid atresia or tricuspid stenosis (APV-TA/TS) is an extremely rare congenital heart defect associated with significant morbidity and mortality. Compared to Tetralogy of Fallot with Absent Pulmonary Valve Syndrome, branch pulmonary arteries are not typically significantly dilated. We present the case of a newborn male prenatally diagnosed APV-TA with intact ventricular septum (IVS) and nearly discontinuous branch pulmonary arteries, the surgical strategy employed, and the salient hemodynamic factors considered in the medical decision-making.

Percutaneous transient occlusion of the transtricuspid flow: a new method to evaluate the right ventricle-dependent coronary circulation in pulmonary atresia with intact ventricular septum.

Pulmonary atresia with an intact ventricular septum is characterised by heterogeneity in right ventricle morphology and coronary anatomy. In some cases, the presence of ventriculocoronary connections may promote coronary artery stenosis or interruption, and aortic diastolic pressure may not be sufficient to drive coronary blood flow. This requires a correct evaluation (currently done by angiography) which depends on whether the patient can be offered decompression of the right ventricle. To date, there is no objective method to do so, so we designed a percutaneous, transitory technique with the purpose of occluding the transtricuspid anterograde flow. The manoeuverer was performed in a 25-day-old female with pulmonary atresia with intact ventricular septum, right ventricle at suprasystemic level, and selective coronarography was not conclusive, the anterior descendant with stenosis in its middle third and from this point, thinner with to-fro flow. Occlusion was performed with a balloon catheter. We re-evaluated the coronary flow and the normalised anterior descendant flow. We hope that with this new method, we can give a more accurate diagnosis and determine the cases in which the coronary circulation is truly not right ventricle dependent to offer a greater number of patients biventricular or 1.5 ventricular repairs and thereby improve their quality of life and survival, the ones that turn out to be right ventricular dependant; offer them an early reference for cardiac transplant or in case it is not available to consider univentricular palliation knowing that this probably would not reduce the risk of ischaemia and/or death over time.

Three- and Four-Dimensional Imaging of Ductus Arteriosus in Fetuses With Pulmonary Atresia and Aortic Arch Abnormalities.

Advances in fetal echocardiography including newer techniques like 4D spatio-temporal image correlation technology has improved our understanding of fetal cardiac and extracardiac abnormalities. High resolution ultrasound combined with color Doppler and 3D rendering have contributed to an improved understanding of the fetal vascular system and its anomalies. This pictorial essay including ultrasound images and videos alongside their respective clay models, provides precise information of duct anatomy in fetuses with pulmonary atresia and aortic arch abnormalities.

A Noninvasive Circulating Signature of Combined Right Ventricular Pressure and Volume Overload in Tetralogy of Fallot/Pulmonary Atresia/Major Aortopulmonary Collateral Arteries.

Background: Despite surgical advances, children with tetralogy of Fallot/pulmonary atresia/major aortopulmonary collaterals (TOF/PA/MAPCAs) are subject to chronic right ventricular (RV) pressure and volume overload. Current diagnostic tools do not identify adverse myocardial remodeling and cannot predict progression to RV failure. We sought to identify a noninvasive, circulating signature of the systemic response to right heart stress to follow disease progression. Methods: Longitudinal data were collected from patients with TOF/PA/MAPCAs (N = 5) at the time of (1) early RV pressure overload and (2) late RV pressure and volume overload. Plasma protein and microRNA expression were evaluated using high-throughput data-independent mass spectroscopy and Agilent miR Microarray, respectively. Results: At the time of early RV pressure overload, median patient age was 0.34 years (0.02-9.37), with systemic RV pressures, moderate-severe hypertrophy, and preserved systolic function. Late RV pressure and volume overload occurred at a median age of 4.08 years (1.51-10.83), with moderate RV hypertrophy and dilation, and low normal RV function; 277 proteins were significantly dysregulated (log2FC ≥0.6/≤-0.6, FDR≤0.05), predicting downregulation in lipid transport (apolipoproteins), fibrinolytic system, and extracellular matrix structural proteins (talin 1, profilin 1); and upregulation in the respiratory burst. Increasing RV size and decreasing RV function correlated with decreasing structural protein expression. Similarly, miR expression predicted downregulation of extracellular matrix-receptor interactions and upregulation in collagen synthesis. Conclusion: To our knowledge, we show for the first time a noninvasive protein and miR signature reflecting the systemic response to adverse RV myocardial remodeling in TOF/PA/MAPCAs which could be used to follow disease progression.

[Post-operative Management After Surgery for Diminutive Branch Pulmonary Arteries].

Congenital severe peripheral pulmonary artery stenosis is usually associated with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral artery. Complications mainly related to respiratory system frequently occur after peripheral pulmonary artery patch augmentation with or without uniforcalization. Pulmonary hemorrhage and airway bleeding can be fatal. Airway compression from surrounding structures such as reconstructed central pulmonary artery, pulmonary hypertension, ventilation/perfusion mismatch, and pulmonary ischemia reperfusion injury are also life-threating complications. Long mechanical ventilator support with positive airway pressure under the deep sedation is a key to success to prevent major complications. Extra corporeal membrane oxygen support should not be hesitated if respiratory and/or hemodynamic conditions are critical. Chylothorax is a risk factor for prolonged intensive care unit stay. Several treatment options are reported, then multidisciplinary treatment with nil per oral and total parenteral nutrition is recommended.

Right Heart Remodeling After Pulmonary Valve Replacement in Patients With Pulmonary Atresia or Critical Stenosis With Intact Ventricular Septum.

Background Patients with pulmonary atresia or critical pulmonary stenosis with intact ventricular septum (PA/IVS) and biventricular circulation may require pulmonary valve replacement (PVR). Right ventricular (RV) remodeling after PVR is well described in tetralogy of Fallot (TOF); we sought to investigate RV changes in PA/IVS using cardiac magnetic resonance imaging. Methods and Results A retrospective cohort of patients with PA/IVS who underwent PVR at Boston Children's Hospital from 1995 to 2021 with cardiac magnetic resonance imaging before and after PVR was matched 1:3 with patients with TOF by age at PVR. Median regression modeling was performed with post-PVR indexed RV end-diastolic volume as the primary outcome. A total of 20 patients with PA/IVS (cases) were matched with 60 patients with TOF (controls), with median age at PVR of 14 years. Pre-PVR indexed RV end-diastolic volume was similar between groups; cases had higher RV ejection fraction (51.4% versus 48.6%; P=0.03). Pre-PVR RV free wall and left ventricular (LV) longitudinal strain were similar, although LV midcavity circumferential strain was decreased in cases (-15.6 versus -17.1; P=0.001). At a median of 2 years after PVR, indexed RV end-diastolic volume was similarly reduced; cases continued to have higher RV ejection fraction (52.3% versus 46.9%; P=0.007) with less reduction in RV mass (Δ4.5 versus 9.6 g/m2; P=0.004). Post-PVR, RV and LV longitudinal strain remained unchanged, and LV circumferential strain was similar, although lower in cases. Conclusions Compared with patients with TOF, patients with PA/IVS demonstrate similar RV remodeling after PVR, with lower reduction in RV mass and comparatively higher RV ejection fraction. Although no differences were detected in peak systolic RV or LV strain values, further investigation of diastolic parameters is needed.