Pulmonary Atresia With Intact Ventricular Septum Research Articles

Pulmonary Atresia with Intact Ventricular Septum, a National Comparison Between Interventional and Surgical Approach, in Combination with a Systemic Literature Review.

This study aimed to compare long-term morbidity in patients with pulmonary atresia with intact ventricular septum (PA-IVS) treated with catheter-based intervention (group A) versus those undergoing heart surgery (group B) as initial intervention. Additionally, we conducted a systematic literature review on PA-IVS treatment. All neonates born in Sweden with PA-IVS between 2007 and 2019 were screened for inclusion. The inclusion criterion was decompression of the right ventricle for initial intervention. Medical records were reviewed, as well as the initial preoperative angiogram, and the diagnostic echocardiogram. Comparisons between groups were performed with Mann-Whitney U-test and Fisher´s exact test. A systematic literature review of original studies regarding treatment of PA-IVS (2002 and onward) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, to assess the outcomes of patients with PA-IVS. 34 (11 females) patients were included, 18 in group A and 16 in group B. There was no mortality in either group. Follow-up time ranged from 2 to 15years (median 9). All attempted perforations in group A were successful, and 16 out of 18 patients reached biventricular circulation. In the surgical group 15 out of 16 patients reached biventricular circulation. The literature review presented heterogeneity in standards for treatment. This retrospective population-based multicenter study demonstrates that both catheter-based intervention and heart surgery are safe procedures. Our results are comparable to, or exceed, those in the systematic literature review. The systematic literature review displays a great heterogeneity in study design, with no definitive golden standard treatment.

Comparison of Ductal Stent Versus Surgical Shunt as Initial Intervention for Neonates with Pulmonary Atresia with Intact Ventricular Septum.

Data comparing surgical systemic-to-pulmonary artery shunt and patent ductus arteriosus (PDA) stent as the initial palliation procedure for patients with pulmonary atresia with intact ventricular septum (PA-IVS) are limited. We sought to compare characteristics and outcomes in a multicenter cohort of patients with PA-IVS undergoing surgical shunts versus PDA stents. We retrospectively reviewed neonates with PA-IVS from 2009 to 2019 in 19 United States centers. Bivariate comparisons and multivariable logistic regression analysis were performed to determine the relationship between initial palliation strategy and outcomes including major adverse cardiovascular events (MACE): stroke, mechanical circulatory support, cardiac arrest, or death. Included were 187 patients were included: 38 PDA stents and 149 surgical shunts. Baseline characteristics did not differ statistically between groups. Post-procedural MACE occurred in 4 patients (11%) with PDA stents versus 38 (26%) with surgical shunts, p = 0.079. Overall, the initial palliation strategy was not significantly associated with MACE (aOR:0.37; 95% CI,0.13-1.02). In patients with moderate-to-severe right ventricle hypoplasia, PDA stents were significantly associated with decreased odds of MACE (aOR:0.36; 95% CI,0.13-0.99). PDA stents were associated with lower vasoactive inotrope scores (median 0 versus 5, p < 0.001), greater likelihood to be extubated at the end of their procedure (37% versus 4%, p < 0.001), and shorter duration of mechanical ventilation (median 24 versus 96h, p < 0.001). PDA stents were associated with significantly more unplanned reinterventions for hypoxemia compared to surgical shunts (42% vs. 20%, p = 0.009). In this multicenter study, neonates with PA-IVS who underwent PDA stenting received less vasoactive and ventilatory support postoperatively compared to those who had surgical shunts. Furthermore, patients with the most severe morphology had decreased odds of MACE.

Surgical outcomes of the systemic-to-pulmonary artery shunt: risk factors of post-operative acute events and effectiveness of regulation of pulmonary blood flow with metal clips.

The aim of this study was to analyze the risk factors for acute events after systemic-to-pulmonary shunt (SPS) and to investigate the effectiveness of pulmonary blood flow regulation with a metal clip. The case histories of 116 patients (78 biventricular [BV] and 38 single ventricle [SV] physiology) who underwent SPS between 2010 and 2021 were retrospectively reviewed. Our strategy was to delay SPS until 1month of age; pulmonary blood flow (PBF) regulation by partial clipping of the graft, if needed. Cases of aortic cross-clamping were excluded from this study. CPB was used in 49 (42%) patients: the median age at SPS was 1month (2days to 16years), and the sternotomy approach in 65. Discharge survival was 98.3% (114/116); hospital death occurred in 1.7% due to coronary ischemia. Inter-stage mortality occurred in 1.7% (shunt thrombosis, 1; pneumonia, 1). Pre-discharge acute events occurred in 7 patients (6.0%): thrombosis 3, pulmonary over-circulation 2, and coronary ischemia 2. Multiple logistic regression analysis revealed that pulmonary atresia with intact ventricular septum (PA/IVS) (p = 0.0253) was an independent risk factor for acute events. Partial clipping of the graft was performed in 24 patients (pulmonary atresia 15) and clip removal was performed by catheter intervention in 9 patients; no coronary ischemic events and graft injury occurred in these patients. Surgical outcomes after SPS were acceptable and metal clip regulation of pulmonary blood flow appears to be safe and effective. PA/IVS was still a significant risk factor for acute events.

Anesthesia in A Patient with Pulmonary Atresia with Intact Ventricular Septum (PA IVS) Underwent Bidirectional Cavo-Pulmonary Shunt (BCPS)

Background: Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare condition, encompassing approximately 1%–3% of congenital heart diseases. Patients with PA-IVS have functional single-ventricle physiology. The ultimate possible outcomes for patients with PA-IVS are biventricular circulation, 1.5-ventricle or single-ventricle palliation, or cardiac transplantation. The bidirectional cavopulmonary shunt (BCPS) procedure directs flow from the superior vena cava into both the right and left pulmonary arteries, permitting flow to both lungs. The shunt is considered to be the second stage of palliation and is generally preparative for the third-stage Fontan procedure. The BCPS improves systemic arterial oxygen saturation without increasing ventricular work or pulmonary vascular resistance.Case: A 10-month-old, 25-day-old boy, weight 9.93 kg, body length 72 cm, diagnosed with PA-IVS, restricted persistent foramen ovale (PFO), right ventricle hypoplastic, and turtuous patent ductus arteriosus (PDA), underwent BCPS, atrial septectomy, and PDA stent evacuation surgery. The patient underwent a PDA stenting and ballooning atrial septectomy (BAS) at 17 days of age at the cathlab. The patient was cyanotic with stable hemodynamics and a saturation of 72% preoperatively.Discussion: Preoperative fasting must be observed to maintain the patient's hydration state. Pulmonary blood flow and systemic blood flow must be balanced. An adequate analgetic can prevent pain stimuli that increase pulmonary vascular resistance. Drugs to reduce the afterload, such as milrinone, are needed. Mechanical ventilation was set to get PaCO2 between 40 and 45 mmHg. Maintain the normal heart beat, preload, and contractility to maintain cardiac output (CO) with saturation 80–85%. Wean from mechanical ventilation as soon as possible.Conclusion: Anesthetic management for BCPS in patients with single ventricles from the preoperative period, intraoperative period, and postoperative period. Understanding single ventricle phsiology is important in order to treat the patient.

Patients With Hypoplastic Left Heart Syndrome Have a Shorter Superior Vena Cava

BackgroundThe primary treatment for hypoplastic left heart syndrome (HLHS) is the Fontan pathway, which entails performing the Glenn procedure. We hypothesized that the superior vena cava in patients with HLHS was short. As the length of the superior vena cava influences the Glenn procedure, we compared its length between patients with HLHS and those with other congenital heart diseases. MethodsPatients with HLHS or its variant, patients with ventricular septal defects (VSD), and patients with pulmonary atresia with intact ventricular septum (PA/IVS)—including critical pulmonary stenosis—were enrolled in this study. The effective superior vena cava ratio (ESCVR), which is defined as the inferior border of the left brachiocephalic vein to the superior surface of the right pulmonary artery/height, was measured. ResultsThe median ESVCR of the HLHS, VSD, and PA/IVS patients was 12.54 mm/m, 17.96 mm/m, and 18.46 mm/m, respectively. ESVCR of the HLHS group was significantly smaller than that of the other groups (P = .0013 vs VSD group, P = .0002 vs PA/IVS group). ConclusionsPatients with HLHS have a relatively short superior vena cava, which may complicate the Glenn procedure.

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 7.52mmHg, 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.

Abstract P1029: Abnormal Progenitor Cell Differentiation And Cardiomyocyte Proliferation In Hypoplastic Right Heart Syndrome

Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare (4-8 per 100,000 live births) type of hypoplastic right heart syndrome (HRHS) where the right-sided structures in the heart are malformed. In PA-IVS, the pulmonary valve that acts to regulate the unidirectional flow of blood from the right ventricle (RV) to the lungs does not open, resulting in no connection between the RV and the pulmonary arteries. After surgical or catheter-based intervention, PA-IVS patients have clinical outcomes that range from single-ventricle palliation to a biventricular repair. Mechanisms underlying the spectrum of RV hypoplasia in PA-IVS are difficult to fully ascribe to an atretic pulmonary valve. There are no reliable animal models available for studying disease mechanisms of PA-IVS. In this study, we leverage patient-specific induced pluripotent stem cells (iPSCs) and single-cell RNA sequencing to elucidate cellular etiologies of ventricular hypoplasia in PA-IVS. PA-IVS iPSC-derived cardiomyocytes are less proliferative compared to controls under both static and cyclic stretch, suggesting that genetic factors may contribute to a spectrum of ventricular hypoplasia in PA-IVS. Single-cell transcriptomic analysis reveals that cell lineage determination towards second heart progenitors is suppressed, with enhanced differentiation into first heart field and epicardial lineages during cardiac differentiation. Additionally, biological pathways associated with cell proliferation and cell cycle progression are downregulated whereas mitochondrial activities are elevated in early cardiomyocytes originated from PA-IVS patients. In conclusion, abnormal cell lineage differentiation and cardiomyocyte proliferation may underlie the cellular and developmental etiologies of ventricular hypoplasia in HRHS.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

A Single-Centre Retrospective Review ofModified Blalock-Taussig Shunts: A22-YearExperience.

This single-centre retrospective study explores demographics and outcomes of patients who underwent a modified Blalock-Taussig shunt (MBTS) over a 22-year period. The predominant surgical approach in this study is a lateral thoracotomy, in contrast to a midline sternotomy. Risks and outcomes of this approach are compared with national and international literature. Demographic, anatomical, clinical, surgical and outcome data of all patients who underwent a MBTS between 2000 and 2022 were collected and analysed, excluding Norwood procedures, which are not performed at this institution. Short- and long-term morbidity and mortality is described. Over the 22-year study period, 185 MBTS were performed in 162 patients, at a median age of 16 days (interquartile range [IQR] 5-59 days) and weight of 3.47 kg (IQR 3-4.25 kg, minimum weight 2 kg). Of these, 79% of patients had a biventricular circulation. Cardiac diagnoses included both univentricular and biventricular anatomy; tetralogy of Fallot (TOF) (36%), transposition of the great arteries/ventricular septal defect/pulmonary stenosis (TGA/VSD/PS) (11%), pulmonary atresia with intact ventricular septum (PA/IVS) (23%), pulmonary atresia with ventricular septal defect (PA/VSD) (14%), other (16%). The most common size of MBTS was 4 mm (71%); 93% were performed via a lateral thoracotomy. There were 47 cases of major operative morbidity, which did not differ significantly with cardiac diagnosis. Overall all-cause mortality was 13.5%. Early operative mortality was 4.3%. Mortality varied with cardiac diagnosis, 6% with TOF and 19% with PA/IVS. There was no era effect on mortality rates, however a lower frequency of major morbidity (23% vs 7%, p=0.03) was observed in the most recent third of the study period. Risk factors for shunt reintervention or mortality included weight <2.5 kg (HR=2.79 [1.37, 5.65], p=0.005), and pre- (HR=3.31 [1.86, 5.9], p<0.001) or postoperative lactic acidosis (HR=1.37 [1.25,1.5], p<0.001). These rates are comparable to those in the literature, with the predominant approach a midline sternotomy. Hobbes etal. from Royal Children's Hospital in Melbourne, Australia reported an overall and operative mortality rate of 12.8% and 5.2%, respectively, while Sasikumar etal. from The Hospital for Sick Children in Toronto, Canada reported an overall and operative mortality of 16% and 10%, respectively, for MBTS procedures over the same time period, however including smaller weight infants. Petrucci etal. described outcomes from the multi-institutional Society of Thoracic Surgeons Congenital Heart Surgery database reporting an overall mortality in MBTS of 7.2% in 1,273 patients with both single and double ventricle anatomy. Mortality rates and risk factors for adverse outcomes are comparable to those previously reported for both univentricular and biventricular groups. These results highlight that outcomes of MBTS performed via lateral thoracotomy are comparable to those by midline sternotomy as reported in the literature. Operating via the lateral approach may be advantageous as it avoids the complications of a midline sternotomy.

Efficacy of transcatheter pulmonary valve perforation in neonates with pulmonary atresia with intact ventricular septum

Objective: To explore the efficacy and safety of transcatheter pulmonary valve perforation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The clinical data on surgical treatment and follow-up in 16 patients with PA-IVS who underwent transcatheter pulmonary valve perforation in Women and Children's Hospital, Qingdao University from October 2018 to October 2021 were analyzed retrospectively. The right ventricular systolic pressure and percutaneous oxygen saturation (SpO2) were compared before and after operation. In addition, the SpO2 and echocardiographic data at preoperative and the last follow-up were compared. Comparisons between groups were performed using paired-samples t test. Results: Among the 16 patients (10 males and 6 females) with the age at operation of 19 (14, 26) days, 12 cases underwent transcatheter pulmonary valve perforation successfully, 2 cases were transferred to surgery department for open-heart pulmonary valvulotomy, and the remaining 2 cases were transmitted to surgery department for transthoracic pulmonary valve perforation. The age at operation of the 12 patients who underwent transcatheter pulmonary valve perforation was 18 (14, 27) days, and the weight was (3.6±0.4) kg. The immediate postoperative right ventricular systolic pressure decreased significantly ((57±16) vs. (95±19) mmHg (1 mmHg=0.133 kPa), t=7.49, P<0.001), and the postoperative SpO2 was improved effectively (0.90±0.48 vs.0.75±0.09, t=-5.61, P<0.001). The follow-up time was 22 (7, 33) months for 12 patients who underwent transcatheter pulmonary valve perforation successfully. At the last follow-up, the ratio of right to left ventricular transverse diameter was significantly higher than that before operative (0.55±0.05 vs. 0.45±0.05, t=-3.27,P=0.007). Furthermore, the Z-scores of pulmonary valvular diameter (-0.78±0.23 vs. -1.73±0.56, t=-8.52, P<0.001) and the tricuspid valvular diameter (-0.52±0.12 vs. -1.46±0.38, t=-10.40, P<0.001) were all significantly higher than preoperative data. At last, all the patients achieved biventricular circulation without death or major complications. Conclusion: Transcatheter pulmonary valve perforation is a safe and effective therapy for neonatal PA-IVS, and its curative effect has been confirmed by the medium follow-up data.

The Utility of CT Angiography in Neonates with Pulmonary Atresia with Intact Ventricular Septum and Concern for Right Ventricular Dependent Coronary Circulation: Case Series.

Up to one third of patients with pulmonary atresia with intact ventricular septum (PA-IVS) will have inadequate anterograde coronary blood flow and rely on fistulous connections from the right ventricle (RV) for myocardial perfusion, known as RV-dependent coronary circulation (RVDCC). Historically, identification of the extent of ventriculocoronary connections and coronary stenosis has required invasive imaging with cardiac catheterization and angiography. Cardiac computed tomography (CCT) potentially provides a less invasive imaging option for therapeutic planning in this group of patients. We describe six neonates with PA-IVS who underwent both CCT and cardiac catheterization at our institution prior to any surgical or transcatheter intervention between 2009 and 2019. Imaging was concerning for RVDCC in all six patients. The average tricuspid Z-score was - 4.19 (2.1 to - 5.34). Two patients underwent cardiac transplantation and two patients underwent ductal stenting. The overall mortality rate was 50%. CCT findings closely mirrored the findings of invasive cardiac catheterization and identified important morphological variations. The average radiation exposure (DLP) per CCT was (10.5mGycm, range 6-20). Technological improvements in CCT have enabled adequate visualization of coronary anomalies in children with comparable accuracy to cardiac catheterization, but considerably less radiation exposure. However, diagnosis of RVDCC requires direct right ventricular angiography. Therefore, the potential benefit of obtaining a CCT prior to catheterization for infants with PA-IVS is the ability to risk stratify, assist with procedural planning, and improve family counseling.

Staged Percutaneous Management of Pulmonary Atresia and Intact Interventricular Septum: Stretching the Limits.

Pulmonary atresia with intact ventricular septum (PA/IVS) can be treated by catheter-based interventions and complemented by various surgical procedures. We aim to determine a long-term treatment strategy to enable patients to be surgery free, depending solely on percutaneous interventions. We selected five patients from among a cohort of patients with PA/IVS treated at birth with radiofrequency perforation and dilatation of the pulmonary valve. Patients had reached a pulmonary valve annulus of 20 mm or larger on their biannual echocardiographic follow-up, with right ventricular dilatation. The findings, together with the right ventricular outflow tract and pulmonary arterial tree, were confirmed by multislice computerised tomography. Based on the angiographic size of the pulmonary valve annulus, all patients were successfully implanted with either Melody® or Edwards® pulmonary valves percutaneously, regardless of their small weights and ages. No complications were encountered. We managed to stretch the age and weight limitations for performing percutaneous pulmonary valve implantation (PPVI): interventions were attempted whenever a pulmonary annulus size of >20 mm was reached, which was rationalised by the prevention of progressive right ventricular outflow tract dilatation and accommodating valves between 24 and 26 mm, which is enough to sustain a normal pulmonary flow in adulthood.

Abstract 14737: Right Heart Remodeling After Pulmonary Valve Replacement in Patients With Pulmonary Atresia With Intact Ventricular Septum and Critical Pulmonary Stenosis

Background: Patients with pulmonary atresia with intact ventricular septum (PA/IVS) and critical pulmonary stenosis (CPS) managed to a biventricular circulation may eventually require pulmonary valve replacement (PVR) for pulmonary regurgitation (PR). Right ventricular (RV) remodeling after PVR has been well described in tetralogy of Fallot (TOF); we sought to investigate RV volumetric and functional changes in PA/IVS using CMR. Methods: A retrospective cohort of PA/IVS and CPS patients who underwent PVR at Boston Children’s Hospital from 1995-2021 with CMR before and after PVR was matched 1:3 with TOF patients by age at PVR. Patients with initial intervention &gt;2 weeks of age or 1.5 ventricle circulation were excluded. Median regression modeling accounting for matching was performed with reduction in indexed right ventricular end diastolic volume (RVEDVi) post PVR as the primary outcome, adjusting for covariates including tricuspid regurgitation (TR) and PVR valve size. Results: Twenty PA/IVS or CPS patients (cases) were matched with 60 TOF (controls), with median age at PVR 14 years; at median follow-up 8 years post PVR, 95% were NYHA Class I. Pre-PVR RVEDVi was similar between groups (165 vs 167 ml/m 2 , p=0.7), although cases had higher RV EF (51.4 vs 48.6%, p=0.03), TR fraction (23 vs 9%, p=0.008), and a trend toward lower RV mass; PR fraction, LV volumes and EF were similar. Pre-PVR RV free wall and LV longitudinal strain were similar, although LV circumferential strain was worse in cases (-15.6 vs -17.1, p=0.01). At median 2 years after PVR, RVEDVi was similarly reduced from 166 to 118 ml/m 2 (p=0.73), although cases had higher RV EF (52.3% vs 46.9%, p=0.007) with less reduction in indexed RV mass (Δ4.5 vs 9.6 g/m 2 , p=0.02); LV volumes and EF were similar. Post PVR, RV and LV longitudinal strain remained unchanged both within and between groups; LV circumferential strain was similar post PVR and remained lower in cases vs controls. Conclusion: Patients with PA/IVS after PVR demonstrate similar RV remodeling to TOF patients, with lesser reduction in RV mass and comparatively better post RV EF. CMR strain imaging found no significant pre-post differences in RV or LV systolic parameters. Further investigation is needed to evaluate for changes in diastolic parameters.

Procedural Outcomes of Pulmonary Atresia With Intact Ventricular Septum in Neonates: A Multicenter Study

BackgroundMulticenter contemporary data describing short-term outcomes after initial interventions of neonates with pulmonary atresia with intact ventricular septum (PA-IVS) are limited. This multicenter study describes characteristics and outcomes of PA-IVS neonates after their initial catheter or surgical intervention and identifies factors associated with major adverse cardiac events (MACE). MethodsNeonates with PA-IVS who underwent surgical or catheter intervention between 2009 and 2019 in 19 centers were reviewed. Risk factors for MACE, defined as cardiopulmonary resuscitation, mechanical circulatory support, stroke, or in-hospital mortality, were analyzed using multivariable logistic regression models. ResultsWe reviewed 279 neonates: 79 (28%) underwent right ventricular decompression, 151 (54%) underwent systemic-to-pulmonary shunt or ductal stent placement only, 36 (13%) underwent right ventricular decompression with shunt or ductal stent placement, and 11 (4%) underwent transplantation. MACE occurred in 57 patients (20%): 26 (9%) received mechanical circulatory support, 37 (13%) received cardiopulmonary resuscitation, stroke occurred in 16 (6%), and 23 (8%) died. The presence of 2 major coronary artery stenoses (adjusted odds ratio, 4.99; 95% CI, 1.16-21.39) and lower weight at first intervention (adjusted odds ratio, 1.52; 95% CI, 1.01-2.27) were significantly associated with MACE. Coronary ischemia was the most frequent presumed mechanism of death (n = 10). ConclusionsIn a multicenter cohort, 1 in 5 neonates with PA-IVS experienced MACE after their initial intervention. Patients with 2 major coronary artery stenoses or lower weight at the time of the initial procedure were most likely to experience MACE and warrant vigilance during preintervention planning and postintervention management.

Generation of an induced pluripotent stem cell line NCHi003-A from a 11-year-old male with pulmonary atresia with intact ventricular septum (PA-IVS)

Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare congenital heart defect defined by membranous or muscular atresia of the right ventricular outflow tract where patients display varying degrees of hypoplasia of the right ventricle. This condition results in cyanosis due to an inability of blood to flow from the right ventricle to the pulmonary arteries, thus requiring immediate surgical intervention after birth. An iPSC line was generated from peripheral blood mononuclear cells of a 11-year-old male patient diagnosed with PA-IVS through Sendai virus-mediated reprogramming. This disease-specific iPSC line was characterized by immunocytochemistry, STR analysis, karyotype analysis, and mycoplasma testing.

Abstract P1016: Modeling Ventricular Hypoplasia In Pulmonary Atresia With Intact Ventricular Septum Using Patient-Specific Induced Pluripotent Stem Cells

Pulmonary atresia with intact ventricular septum (PA-IVS) is a detrimental congenital heart disease where the pulmonary valve is not appropriately developed. Several hypotheses speculated to explain the pathogenesis of this disorder contains abnormal coronary arterial development, atypical blood flow through venous valve and atretic pulmonary valve formation. Conventional treatment strategy is pulmonary valve perforation, and PA-IVS patients after treatment present with varying degrees of ventricular hypoplasia: from single ventricle palliation (1v) to 1½-ventricle palliation (1.5v) and bi-ventricle repair (2v). Mechanistic studies are required to further explain the different levels of RV hypoplasia in PA-IVS patients. Here, we generated PA-IVS-specific induced pluripotent stem cells (iPSCs) from patients with a spectrum of RV hypoplasia. PA-IVS iPSC-derived cardiomyocytes (iPSC-CMs) contracted normally and displayed sarcomeric structures with intercalated cardiac troponin T and α-actinin. Early-stage PA-IVS iPSC-CMs exhibited a variety of compromised proliferation activities, which were not able to be rescued by Wnt signaling pathway activation. Transcriptomic profiling by bulk RNA seq suggested that pathways involved in the cell cycle and mitosis were downregulated in day13 PA-IVS-1v iPSC-CMs, but not in PA-IVS-2v iPSC-CMs. However, at later stage (day20), pathways involved in the regulation of cell division and mitosis was upregulated in PA-IVS-1v cardiomyocytes, indicating a possible developmental delay in the cardiomyocyte proliferation for PA-IVS-1v. Intriguingly, differentially expressed genes between PA-IVS-2v and control CMs were mostly enriched in the pathways relevant to glucose metabolism, mitochondrial biogenesis, and muscle contraction. The differentially involved pathways between PA-IVS-1v and PA-IVS-2v cardiomyocytes suggest that an intrinsic transcriptional program may lead to divergent degrees of cardiomyocyte proliferation and ventricular growth in PA-IVS. We conclude that patient iPSC-CMs can recapitulate cardiomyocyte proliferation defects which are involved in ventricular hypoplasia in PA-IVS.

Valvuloplasty of fetal pulmonary atresia with intact ventricular septum and hypoplastic right heart: Mid-term follow-up results

ObjectiveThis study aimed to analyze and evaluate the results of mid-term follow-up after fetal pulmonary valvuloplasty (FPV) in fetuses with pulmonary atresia with intact ventricular septum (PA/IVS). MethodsFrom August 31, 2018, to May 31, 2019, seven fetuses with PA/IVS and hypoplastic right heart were included in this study. All underwent echocardiography by the same specialist and were operated on by the same team. Intervention and echocardiography data were collected, and changes in the associated indices noted during follow-up were analyzed. ResultsAll seven fetuses successfully underwent FPV. The median gestational age at FPV was 27.54 weeks. The average FPV procedural time was 6 ​min. Persistent bradycardia requiring treatment occurred in 4/7 procedures. Finally, five pregnancies were successfully delivered, and the other two were aborted. Compared to data before fetal cardiac interventions (FCI), tricuspid valve annulus diameter/mitral valve annulus diameter (TV/MV) and right ventricle diameter/left ventricle diameter (RV/LV) of all fetuses had progressively improved. The maximum tricuspid regurgitation velocity decreased from 4.60 ​m/s to 3.64 ​m/s. The average follow-up time was 30.40 ​± ​2.05 months. During the follow-up period, the diameter of the tricuspid valve ring in five children continued to improve, and the development rate of the tricuspid valve was relatively obvious from 6 months to 1 year after birth. However, the development of the right ventricle after birth was relatively slow. It was discovered that there were individual variations in the development of the right ventricle during follow-up. ConclusionThe findings support the potential for the development of the right ventricle and tricuspid valve in fetuses with PA/IVS who underwent FCI. Development of the right ventricle and tricuspid valve does not occur synchronously during pregnancy. The right ventricle develops rapidly in utero, but the development of tricuspid valve is more apparent after birth than in utero.

Pulmonary Artery Development Over Time in Severe Ebstein Anomaly.

Recently, the outcome of severe Ebstein anomaly (EA) has improved with the prevalence of the Starnes procedure. However, time-dependent changes in the size of the central pulmonary artery (PA) have not been fully understood. A retrospective chart review of patients with EA who underwent the Starnes procedure during the neonatal period and those with pulmonary atresia with intact ventricular septum (PAIVS) was performed at Fukuoka Children's Hospital. There were 14 patients in the severe EA group and 36 in the PAIVS group, with mean observational periods of 3.8 and 4.2years, respectively. No significant difference in survival was observed between the groups. However, the mean size of the central PA was smaller in the severe EA group at each surgical stage (after systemic-to-pulmonary shunt, after the bidirectional Glenn procedure, and after the Fontan procedure). A significantly larger ventricular volume was observed in the severe EA group after the Fontan procedure. The growth of the central PA was poor in patients with severe EA. Patients with severe EA should be carefully monitored in this regard both before and after undergoing the Fontan procedure. Further studies regarding long-term prognosis are expected.

Type I and II pulmonary atresia with intact ventricular septum in infants: a 10-year experience in initial surgery at one center

BackgroundTo explore the effect of initial surgery for type I and II pulmonary atresia with intact ventricular septum (PA/IVS).Methods50 children with type I PA/IVS and 50 with type II PA/IVS who had undergone initial surgery were enrolled. Children with Type I were divided into groups A (n = 25) and B (n = 25). Group A had received BT shunt combined with PDA ligation and balloon dilatation of pulmonary valve, whereas group B had undergone BT shunt combined with PDA ligation and pulmonary valve incision. Children with type II were divided into groups C (n = 25) and D (n = 25). Group C had received BT shunt combined with PDA ligation, right ventricular outflow tract (RVOT) incision and transannular patch. Group D had undergone BT shunt combined with PDA ligation, RVOT incision, transannular patch and artificial pulmonary valve implantation. The differences in mechanical ventilation time, length of ICU stay, mortality rate, tricuspid Z value, tricuspid regurgitation, oxygen saturation, pulmonary regurgitation, McGoon ratio, pulmonary artery transvalvular pressure, survival rate were compared between groups A and B, between groups C and D respectively.ResultsThe ventilator assistance time and length of ICU stay were greater in group C than in group D (80.96 ± 8.42 h vs. 65.16 ± 4.85 h, P = 0.045; 222.00 ± 11.72 h vs. 162.48 ± 7.91 h, P = 0.048). The pulmonary artery transvalvular pressure was significantly higher in group A than in group B at 3, 6, 12, 24 and 36 months after surgery (64.86 ± 4.13 mmHg vs. 53.04 ± 5.64 mmHg, P = 0.045; 69.47 ± 1.93 mmHg vs. 55.95 ± 4.04 mmHg, P = 0.005; 80.16 ± 3.76 mmHg vs. 73.24 ± 2.34 mmHg, P = 0.035; 62.95 ± 5.64 mmHg vs. 48.47 ± 7.44 mmHg, P = 0.04; 53.69 ± 4.89 vs. 45.77 ± 3.26, P = 0.02). Furthermore, the tricuspid Z value was significantly greater in group B than in group A at 3 and 24 months after surgery (− (1.37 ± 0.04) vs. − (1.43 ± 0.06), P = 0.03; − (0.41 ± 0.06) vs. − (0.51 ± 0.11), P = 0.02).ConclusionsThe effect of BT shunt combined with PDA ligation and pulmonary valve incision is superior to BT shunt combined with PDA ligation and balloon dilatation of pulmonary valve, and the effect of BT shunt combined with PDA ligation, RVOT incision, transannular patch and artificial pulmonary valve implantation is superior to BT shunt combined with PDA ligation, RVOT incision and transannular patch.

Clinical Outcomes of Pulmonary Atresia With Intact Ventricular Septum (PA/IVS) Cases in Western Australia

Pulmonary atresia with intact ventricular septum (PA/IVS) remains a challenge given the heterogeneity of the lesion. The objective was to define the clinical and surgical profile of patients with PA/IVS in Western Australia.