Bicuspidisation of unicuspid stenotic pulmonary valve in a nine-year-old male.

We report the case of a 9-year-old male with severe congenital pulmonary valve stenosis referred to our centre for percutaneous valvotomy. On admission, trans-thoracic echocardiogram confirmed a unicuspid pulmonary valve with a peak/mean pulmonary valve gradient of 91/53 mmHg and a pulmonary annulus of 13.8 mm (-0.8 Z Score). It also showed an enlarged RV (RV/LV ratio 0,9). During cardiac catheterisation, an additional atrial septal defect (secundum) with significant left to right shunt (Qp/Qs > 2) was diagnosed, which was not amenable to percutaneous closure. The patient was referred for surgical repair.The atrial septal defect was closed by a direct running suture. The repair of the unicuspid valve consisted in bicuspidisation by a large commissurotomy to the left anterior wall of the pulmonary artery. The neo-commissure was created with two separate patches of autologous pericardium secured to the wall of the pulmonary root. The adjustment of the effective height of the pulmonary valve leaflets was done by trimming the patches and a triangular plication of the newly created posterior leaflet. Perioperative echocardiogram showed a peak gradient of 15 mm Hg and trivial pulmonary regurgitation. The total cross-clamp time was 92 min and the bypass time 123 min with a favourable evolution after the surgery.The particularity of the case is represented by the complexity of the bicuspidisation procedure. Using this technique, a tailored approach is needed for every patient.

Management of right ventricular outflow tract with percutaneous Melody valve implantation in pediatric patients: experience in a high complexity center in Colombia.

BACKGROUND: Congenital heart disease poses a therapeutic challenge, specifically pulmonary valve stenosis. This has been treated for many years with invasive procedures and bioprostheses, which over time, become dysfunctional due to the accumulation of fibrous tissue and calcification. OBJECTIVE: The aim of this study is to describe the use of endovascular management in the right ventricular outflow tract, as the beginning of an ongoing effot to improve pediatric outcomes in developing countries. METHODS: Seven pediatric patients with endovascular management of the right outflow tract are presented. Three of them underwent surgical valvuloplasty with persistent pulmonary stenosis. They decided to insert a percutaneous transcatheter pulmonary valve (PPVI) with a Melody valve using the valve-in-valve technique, with 100% stenosis and no complications associated with the procedure. RESULTS: Four patients with successful percutaneous valve implantation had different congenital heart diseases. In addition, the case of a patient in whom an intentional pulmonary valve fracture was performed, an innovative procedure in pediatric endovascular management in the country, is highlighted. CONCLUSIONS: The procedure was minimally invasive, safe, and effective. The IVPP technique could be a viable option in our country for managing failed primary valve implantations or even in native tracts.

ANTECEDENTES: Las cardiopatías congénitas plantean un desafío terapéutico, específicamente la estenosis de la válvula pulmonar. Esta ha sido tratada durante muchos años con procedimientos invasivos e inserción de bioprótesis, que con el tiempo se vuelven disfuncionales y pueden reestenosarse por acumulación de tejido fibroso y calcificación. Debido a las complicaciones generadas por la injuria quirúrgica, se han descrito medidas menos invasivas para el manejo de la estenosis residual e inicial por medios endovasculares en adultos y más recientemente en población pediátrica. OBJETIVO: El objetivo de este reporte es describir la misma en el manejo endovascular del tracto de salida del ventrículo derecho, como el inicio de un trabajo continuo para la mejoría de los resultados pediátricos en países en vía de desarrollo. MÉTODOS: Se presentan siete casos pediátricos de manejo endovascular del tracto de salida derecho; tres de ellos sometidos a valvuloplastia quirúrgica con persistencia de la estenosis pulmonar, por lo cual se decidió inserción percutánea de una válvula pulmonar (IVPP) transcatéter con válvula Melody utilizando la técnica valve-in-valve, con lo que se consiguió una resolución del 100% de la estenosis y no se presentó ningún tipo de complicación asociada al procedimiento. RESULTADOS: En cuatro pacientes se logró una implantación exitosa de la válvula por vía percutánea en diferentes cardiopatías congénitas, siendo uno de ellos en tracto nativo; además, destaca el caso de un paciente en quien se realizó fractura intencional de la válvula pulmonar, procedimiento innovador en el manejo endovascular pediátrico en Colombia. CONCLUSIONES: En estos pacientes el procedimiento resultó ser poco invasivo, seguro y efectivo. La técnica IVPP podría ser considerada una opción viable en Colombia (y en otros países en desarrollo) para el manejo de implantes valvulares primarios fallidos o incluso en tractos nativos.

Prenatal Predictors for Pulmonary Balloon Valvuloplasty in the Newborn.

Pulmonary balloon valvuloplasty (PBV) is the treatment of choice for subjects with isolated pulmonary valve stenosis (IPS). The purpose of this study was to define fetal echocardiographic features associated with an inpatient PBV prior to newborn hospital discharge and characterize resource utilization of IPS fetuses among participating centers. Six center, retrospective case series of singleton fetuses identified between 2010 and 2020 with IPS. Third-trimester echocardiogram data was compared with postnatal data, included pulmonary valve Doppler velocities, pulmonary valve insufficiency and ductus arteriosus flow direction. Comparison between subjects who underwent inpatient PBV during their newborn hospital admission versus those infants referred for outpatient PBV after initial hospital discharge. We analyzed data by logistic regression, student t test and Chi-Square testing with a p value of ≤ 0.05 considered statistically significant. Forty-nine IPS fetuses were identified. Thirty-eight (78%) underwent inpatient PBV at 5 (range 1-58) days and 11 (22%) underwent outpatient PBV at 51.8 (11-174) days. Newborns requiring an inpatient PBV were more likely to have one or more characteristics on 3rd-trimester fetal echocardiogram: left to right or bidirectional ductus arteriosus flow (61% vs 0%), and/or a peak pulmonary valve velocity > 3.0 m/s (odds ratio 16.9, 95% confidence interval 3.02-94.17) with a sensitivity of 90.4% and specificity of 97.7%. Ductus arteriosus flow direction and pulmonary valve peak velocity in the 3rd trimester can successfully predict the need for newborn inpatient PBV. We speculate these findings may be useful in choosing delivery site for the pregnancy complicated by fetal IPS.

Anesthetic management of fetal pulmonary valvuloplasty: A case report.

Anesthesia management of fetal pulmonary valvuloplasty (FPV) is difficult, requiring careful consideration of both the mother and the fetus. Few reports have been published on specific anesthesia implementation and intraoperative management. We report the case of a pregnant woman who was treated with FPV under combined spinal epidural anesthesia (CSEA) with dexmedetomidine in the second trimester of pregnancy. Meanwhile, the application of fetal anesthesia through the umbilical vein was optimal. During the operation, the vital signs of the pregnant woman were stable with no complications and the fetal bradycardia was corrected by intracardiac injection of epinephrine. Four months postoperatively, a boy was born alive by full-term transvaginal delivery. CSEA may be a suitable anesthesia method for FPV surgery. Nevertheless, maternal hemodynamic stability maintenance, effective fetal anesthesia, and timely fetal resuscitation were necessary.

Fenestration: Integrating Wings Into the Atrial Septal Occluder for Navigating a Challenging Terrain.

Background Atrial septal defect (ASD) closure with significant left-to-right shunt and concurrent comorbidities poses challenges for intervention. A fenestrated atrial septal defect (FASD) device is a viable option for patients who cannot undergo complete occlusion due to hemodynamic and medical reasons. This study explores the use of FASD occluders in patients with secundum ASD and associated comorbidities where complete occlusion is difficult. Methodology This retrospective study collected the details of patients recommended for FASD closure diagnosed with significant secundum ASD and who had additional comorbidities between July 2015 and July 2023 in a tertiary cardiac center in eastern India. Among this cohort, patients who underwent FASD device placement were subjected to a comprehensive analysis. Results In total, 16 patients diagnosed with secundum ASD, characterized by significant left-to-right shunt and concurrent comorbidities, were considered for FASD closure during the study period. Ultimately, 13 patients (first group) underwent fenestrated atrial septal occluder implantation. The average age was 45.07 years, with the majority being females (n = 9). Comorbidities among this cohort included substantial left ventricular diastolic dysfunction (n = 7), left ventricular diastolic dysfunction coupled with moderate pulmonary hypertension (n = 1), severe pulmonary hypertension (n = 1), severe pulmonary valvular stenosis with right ventricular diastolic dysfunction (n = 2), and systemic lupus erythematosus (SLE) (n = 2). From this cohort, three patients did not undergo the intervention. The second group consisted of an elderly patient with severe left ventricular diastolic dysfunction, a young adult with a history of left atrial arrhythmia, and a child with Duchenne muscular dystrophy (DMD). The average ASD size among patients who underwent the intervention was 26.38 mm, with a thick-to-thick dimension measuring 31.15 mm. The procedure was successful in all 13 patients, with the most frequently used device being a 34 mm occluder (range = 28-40 mm). All devices, excluding the initial one, were custom-made atrial septal occluders (Lifetech Scientific). Among the patients, 12 exhibited left-to-right fenestration flow, while one patient experienced fenestration constriction, likely due to occluder overcrowding. The first patient had a handmade 5 mm fenestration in a 40 mm Amplatzer septal occluder, which got closed off at the one-year follow-up. The procedure was well-tolerated hemodynamically in all patients, with no major complications during the peri-procedural period. Short-term follow-up indicated favorable patient progress. Conclusions FASD closure emerges as a pivotal alternative for intricate scenarios involving secundum ASD coupled with concurrent comorbidities, offering individualized tailored solutions. Alongside the conventional associated comorbidities, such as left ventricular diastolic dysfunction and pulmonary hypertension, FASD devices hold the potential to extend their benefits to patients grappling with other complexities, including severe pulmonary valvular stenosis, SLE, predisposition to left atrial arrhythmia, and conditions like DMD. Ensuring meticulous evaluation of patient suitability and providing ongoing vigilant care becomes paramount for achieving optimal outcomes. The validation of these findings and the broadening of the comprehension of this approach necessitate further comprehensive investigations.

Exploring the Role of Modified Vascular Anatomical Molding (MVAM) in Prenatal Diagnosis Teaching and Prognosis Prediction of Fetal Complex Congenital Heart Disease (CCHD): A Preliminary Study.

Objective: The present study aimed to explore the role of modified vascular anatomical molding (MVAM) in prenatal diagnosis teaching and prognosis prediction of fetal complex congenital heart disease (CCHD). Methods: Step 1, MVAM method was used to cast the micro-blood vessels and trachea of 52 CCHD specimens. Subsequently, 52 MVAMs were analyzed and compared with the prenatal ultrasound to summarize their characteristics, misdiagnosis and MVAM's teaching role. Step 2, the surgical and follow-up data of 206 CCHD cases were retrospectively analyzed. Cases that evolved into critical illnesses or died within 1-3 years after surgery (poor prognosis) were classified into the study group (n = 77) and those with good prognosis into the control group (n = 129), which were split into the training set and the test set in the ratio 7:3 based on the time cut-off. In the training set, the prognosis of CCHD was predicted using the MVAM anatomical soft markers (distortion and narrowing of aorta/pulmonary artery, right ventricular infundibulum, etc.) and the decision curve analysis (DCA) performed. The model was validated using the test set, and a nomogram was finally established. Results: It was observed that all 52 CCHD cases were confirmed using MVAM. A total of 91 cardiac malformations were recorded, among which 41 malformations were misdiagnosed, and 29 malformations were missed by the prenatal echocardiography. The MVAM method has a good teaching/feedback effect on prenatal diagnosis. The combined model exhibited a higher predictive performance in the training- and test-set. Its high clinical net benefit was proved by DCA. Additionally, the nomogram established using the combined model received a favorable response in clinical practice. Conclusion: The research results indicated that MVAM improved the prenatal diagnosis teaching and training performance. The combined model established based on MVAM anatomical soft markers can offer a high clinical significance for prognosis prediction of CCHD.

Acute Changes in Right Ventricular Function in Pediatric Patients with Pulmonary Valve Stenosis Undergoing Percutaneous Valvuloplasty: A Speckle-Tracking Study.

INTRODUCTION: Pulmonary valve stenosis determines multiple effects on the right ventricular dimension and function. Percutaneous balloon valvuloplasty is the treatment of choice in severe pulmonary valve stenosis in patients of all ages. However, little is known regarding right ventricular function immediate changes after percutaneous balloon dilation. Pediatric patients with isolated pulmonary valve stenosis represent a pure clinical model of chronic RV pressure overload not affected by other confounders or comorbidities. AIM OF THE STUDY: This study seeks to explore right ventricle (RV) mechanics in pediatric patients early after percutaneous balloon pulmonary valvuloplasty (BPV) for valvar pulmonary stenosis (PS). MATERIALS AND METHODS: Forty-three pediatric patients (19 males), mean age 3.2 ± 4.9 years old, with severe pulmonary valve stenosis and indication for percutaneous balloon valvuloplasty were recruited. All patients underwent standard transthoracic echocardiography (TTE), and speckle-tracking echocardiography (STE) with an analysis of right ventricle free-wall longitudinal strain (RVFWLS) one day before and one day after the procedure. For each patient, we collected invasive parameters during the interventional procedure before and after BPV. RESULTS: After the procedure, there was an immediate significant reduction in both peak-to-peak transpulmonary gradient (peak-to-peak PG) and ratio between the right ventricle and aortic systolic pressure (RV/AoP) with a drop of ∆29.3 ± 14.67 mmHg and ∆0.43 ± 0.03, respectively. Post-procedural echocardiography showed peak and mean transvalvar pressure gradient drop (∆50 ± 32.23 and ∆31 ± 17.97, respectively). The degree of pulmonary valve regurgitation was mild in 8% of patients before the procedure, affecting 29% of our patients post-BPV (p = 0.007). The analysis of right ventricular mechanics showed a significant improvement of fractional area change (FAC) immediately after BPV (40.11% vs. 44.42%, p = 0.01). On the other hand, right ventricular longitudinal systolic function parameters, TAPSE and global RVFWLS, did not improve significantly after intervention. The segmental analysis of the RVFWLS showed a significant regional increase in the myocardial deformation of the apical segments. CONCLUSIONS: Percutaneous BPV represents an efficient and safe procedure to relieve severe pulmonary valve stenosis. The analysis of the right ventricular function on echocardiography demonstrated an immediate global systolic function improvement, while longitudinal systolic function was persistently impaired 24 h after intervention, possibly due to the necessity of a longer recovery time.

Pulmonary Valve Stenosis: From Diagnosis to Current Management Techniques and Future Prospects.

Pulmonary stenosis (PS) is mainly a congenital defect that accounts for 7-12% of congenital heart diseases (CHD). It can be isolated or, more frequently, associated with other congenital defects (25-30%) involving anomalies of the pulmonary vascular tree. For the diagnosis of PS an integrated approach with echocardiography, cardiac computed tomography and cardiac magnetic resonance (CMR) is of paramount importance for the planning of the interventional treatment. In recent years, transcatheter approaches for the treatment of PS have increased however, meaning surgery is a possible option for complicated cases with anatomy not suitable for percutaneous treatment. The present review aims to summarize current knowledge regarding diagnosis and treatment of PS.

Pulmonary valve stenosis in a recipient twin in twin-to-twin transfusion syndrome with successful balloon valvuloplasty after birth: a case report.

BACKGROUND: Pulmonary stenosis (PS) is a congenital heart diseases (CHDs) with a spectrum of stenosis. Monochorionic (MC) twins are at increased risk of CHDs, especially acquired CHDs in twin-twin transfusion syndrome (TTTS). PS/Pulmonary atresia (PA) is a rare coincidence with TTTS. MC twin pregnancies have increased in last decades due to increasing in maternal age and extensive use of assisted reproductive technologies. Therefore, attention to this group is important for heart abnormalities, especially in twins with TTTS. Multiple cardiac abnormalities in MC twins with TTTS are to be expected due to cardiac hemodynamic changes and may be eliminated by Fetoscopic laser photocoagulation treatment. Prenatal diagnosis of PS is necessary given the importance of treatment after birth. CASE PRESENTATION: We here present a case of coexistence of TTTS with PS in a growth restricted recipient twin who successfully treated with balloon pulmonary valvuloplasty in neonatal period. Also, we detected infundibular PS after valvuloplasty that treated with medical therapy (propranolol). CONCLUSIONS: It is important to detect acquired cardiac abnormalities in MC twins with TTTS, and follow them up after birth to determine the need of intervention in neonatal period.

Treatment of Congenital Afibrinogenemia in a Neonate With Critical Pulmonary Stenosis.

Fibrinogen deficiencies in neonates can lead to bleeding complications. In this report, we describe a case of congenital afibrinogenemia in a newborn with critical pulmonary stenosis who presented with bilateral cephalohematomas after an uncomplicated delivery. The initial use of cryoprecipitate was followed by administration of fibrinogen concentrate. We estimated a half-life of 24 to 48 hours with the concentrate product. This patient received fibrinogen replacement and had a subsequent successful cardiac repair. The drug's shorter half-life in this neonate contrasts with prior reports of longer half-life in older patients and is important to note in treating future neonatal patients with this diagnosis.

A Systematic Review of Benefits and Risks of Fetal Surgery for Congenital Cardiac Defects Such as Pulmonary Valve Stenosis and Critical Aortic Stenosis.

INTRODUCTION: Congenital heart diseases (CHDs) constitute the most prevalent congenital pathology, and they are a consequence of structural and functional abnormalities during fetal development. The etiology of CHD involves the interaction of genetic and environmental factors. Fetal cardiac surgery aims at preventing natural pathways of CHD in utero, mitigating progression to more complex abnormalities. The goal of this review was to demonstrate the benefits and risks of fetal interventions in the two most prevalent CHDs, pulmonary stenosis and pulmonary atresia with an intact ventricular septum, but also critical aortic stenosis and hypoplastic left heart syndrome. METHODS: Original and relevant articles were selected by meta-aggregation to perform a qualitative analysis of fetal cardiac interventions for pulmonary stenosis and critical aortic stenosis. The Joanna Briggs Institute's Qualitative Assessment and Review Instrument (or JBI-QARI) was used for data quality appraisal. RESULTS: Of 61 potential articles, 13 were selected, and nine were finally included. Discussion: The present review demonstrated that fetal cardiac surgery increases right ventricular growth and hemodynamic flow in pulmonary stenosis, whereas in critical aortic stenosis it enables growth of the left ventricle and increases left ventricular pressure. However, it has a high complication rate, along with considerable morbidity and mortality. CONCLUSION: The benefits of fetal cardiac surgery for pulmonary stenosis and critical aortic stenosis are well-described in the literature; however, there is a significant risk of complications which can be reduced by the surgeon's technical expertise and well-structured hospital facilities.

Cardiac features of Noonan syndrome in Japanese patients.

BACKGROUND: Cardiovascular disease is one of the most important problems in long-term follow-up for Noonan syndrome. We examined cardiovascular issues and clinical manifestations, with a focus on the cardiovascular disease and prognosis of patients with Noonan syndrome. METHODS: This single-centre study evaluated patients who were clinically and genetically diagnosed with Noonan syndrome. RESULTS: Forty-three patients diagnosed with Noonan syndrome were analysed. The most prevalent responsible mutation was found in PTPN11 (25/43). The second and third most prevalent causative genes were SOS1 (6/43) and RIT1 (5/43), respectively, and 67.4% of genetically diagnosed patients with Noonan syndrome had structural cardiovascular abnormalities. Pulmonary valve stenosis was prevalent in patients with mutations in PTPN11 (8/25), SOS1 (4/6), and RIT1 (4/5). Hypertrophic cardiomyopathy was found in two of three patients with mutations in RAF1. There was no difference in the cardiovascular events or cardiovascular disease prevalence in patients with or without PTPN11 mutations. The proportion of RIT1 mutation-positive patients who underwent intervention due to cardiovascular disease was significantly higher than that of patients with PTPN11 mutations. Patients who underwent any intervention for pulmonary valve stenosis exhibited significantly higher pulmonary flow velocity than patients who did not undergo intervention, when they visited our hospital for the first time. All patients who underwent intervention for pulmonary valve stenosis had a pulmonary flow velocity of more than 3.0 m/s at first visit. CONCLUSIONS: These findings suggest that genetic information can provide a clinical prognosis for cardiovascular disease and may be part of genotype-based follow-up in Noonan syndrome.

A Systematic Review of Benefits and Risks of Fetal Surgery for Congenital Cardiac Defects Such as Pulmonary Valve Stenosis and Critical Aortic Stenosis

ABSTRACT Introduction: Congenital heart diseases (CHDs) constitute the most prevalent congenital pathology, and they are a consequence of structural and functional abnormalities during fetal development. The etiology of CHD involves the interaction of genetic and environmental factors. Fetal cardiac surgery aims at preventing natural pathways of CHD in utero, mitigating progression to more complex abnormalities. The goal of this review was to demonstrate the benefits and risks of fetal interventions in the two most prevalent CHDs, pulmonary stenosis and pulmonary atresia with an intact ventricular septum, but also critical aortic stenosis and hypoplastic left heart syndrome. Methods: Original and relevant articles were selected by meta-aggregation to perform a qualitative analysis of fetal cardiac interventions for pulmonary stenosis and critical aortic stenosis. The Joanna Briggs Institute's Qualitative Assessment and Review Instrument (or JBI-QARI) was used for data quality appraisal. Results: Of 61 potential articles, 13 were selected, and nine were finally included. Discussion: The present review demonstrated that fetal cardiac surgery increases right ventricular growth and hemodynamic flow in pulmonary stenosis, whereas in critical aortic stenosis it enables growth of the left ventricle and increases left ventricular pressure. However, it has a high complication rate, along with considerable morbidity and mortality. Conclusion: The benefits of fetal cardiac surgery for pulmonary stenosis and critical aortic stenosis are well-described in the literature; however, there is a significant risk of complications which can be reduced by the surgeon's technical expertise and well-structured hospital facilities.

Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome.

Infants with Noonan Syndrome and hypertrophic cardiomyopathy have a poor prognosis and a high mortality especially when diagnosed before six months of age. As for the majority of the RASopathies, no medical treatment has been approved for Noonan Syndrome. Meanwhile, several approved agents targeting the same RAS/MAPK signaling pathway are used in cancer treatment. In this case report we describe a child with Noonan Syndrome caused by a pathogenic RIT1 variant, who developed severe early-onset hypertrophic cardiomyopathy and pulmonary valve stenosis. She received off-label treatment with the MEK-inhibitor trametinib which resulted in complete remission of the cardiac hypertrophy and a significant improvement of the pulmonary valve stenosis. Our case emphasizes the potential of existing cancer agents targeting the RAS/MAPK signaling pathway as successful treatment for RASopathy manifestations.

Prevalence of Genetic Diagnoses in a Cohort With Valvar Pulmonary Stenosis.

BACKGROUND: Valvar pulmonary stenosis (vPS) accounts for 8% to 12% of congenital heart disease cases. Multiple genetic syndromes are associated with vPS, most commonly Noonan syndrome, but the cause is unknown in most cases. We analyzed genomic data from a large cohort with vPS to determine the prevalence of genetic diagnosis. METHODS: The Pediatric Cardiac Genomics Consortium database was queried to identify probands with vPS without complex congenital heart disease or aneuploidy and with existing whole exome or genome sequencing. A custom analysis workflow was used to identify likely pathogenic or pathogenic variants in disease-associated genes. Demographic and phenotypic characteristics were compared between groups with and without molecular diagnoses. RESULTS: Data from 119 probands (105 trios) were included. A molecular diagnosis was identified in 22 (18%); 17 (14%) had Noonan syndrome or a related disorder. Extracardiac and neurodevelopmental comorbidities were seen in 67/119 (56%) of probands. Molecular diagnosis was more common in those with extracardiac and neurodevelopmental phenotypes than those without (18/67 versus 4/52, P=0.0086). CONCLUSIONS: Clinicians should have high suspicion for a genetic diagnosis in individuals with vPS, particularly if additional phenotypes are present. Our results suggest that clinicians should consider offering sequencing of at least the known congenital heart disease and RASopathy genes to all individuals with vPS, regardless of whether that individual has extracardiac or neurodevelopmental phenotypes present.

Cardiovascular Abnormalities and Gene Mutations in Children With Noonan Syndrome.

Background: Common cardiac abnormalities in Noonan syndrome (NS) include congenital heart diseases (CHD), pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Molecular diagnoses are enabling earlier and more precise diagnosis of patients who have a subtle or atypical presentation. The aims of this study were to investigate genotype-phenotype associations with respect to Noonan syndrome (NS)-associated cardiac abnormalities and catheter or surgery-based interventions conditions. Methods: From January 2019 to December 2021, 22 children with a confirmed molecular diagnosis of NS combined with cardiovascular abnormalities were consecutively enrolled into the current study. A comprehensive review was carried out of echocardiography and electrocardiogram results, second-generation whole-exome sequencing results and catheter or surgery-based interventions conditions. Results: The main manifestations of electrocardiogram abnormalities were QTc prolongation, abnormal Q wave in the precordial lead and limb lead, right ventricular hypertrophy and left or right deviation of the electrical axis. The most commonly detected abnormality was pulmonary valve dysplasia with stenosis, seen in 15 (68.2%) patients, followed by atrial septal defect in 11 (50%) patients. Seven genes (RAF1, RIT1, SOS1, PTPN11, BRAF, SOS2, and LZTR1) were found to contain disease-associated variants. The most commonly observed genetic mutations were PTPN11 (27%) and RAF1 (27%). Each genotype was associated with specific phenotypic findings. RIT1, SOS1, PTPN11, and SOS2 had common echocardiography features characterized by pulmonary valve stenosis, while RAF1 was characterized by HCM. Interestingly, patients with BRAF mutations were not only characterized by HCM, but also by pulmonary valve stenosis. In the cohort there was only one patient carrying a LZTR1 mutation characterized by left ventricle globose dilation. Ten cases underwent catheter or surgery-based interventions. All the operations had immediate results and high success rates. However, some of the cases had adverse outcomes during extended follow-up. Based on the genotype-phenotype associations observed during follow-up, BRAF and RAF1 genotypes seem to be poor prognostic factors, and multiple interventions may be required for NS patients with severe pulmonary stenosis or myectomy for HCM. Conclusions: The identification of causal genes in NS patients has enabled the evaluation of genotype-cardiac phenotype relationships and prognosis of the disease. This may be beneficial for the development of therapeutic approaches.

Timing of pulmonary valve replacement: can we use the same volumetric thresholds in repaired tetralogy of Fallot and pulmonary stenosis?

The timing of pulmonary valve replacement in patients with pulmonary regurgitation following treatment of pulmonary stenosis is undefined. Although cardiac magnetic resonance-based right ventricular volumes in tetralogy of Fallot patients have been used as a guide in pulmonary stenosis patients, anatomic differences between tetralogy of Fallot and pulmonary stenosis patients complicate their application to pulmonary stenosis patients and could result in late referral for pulmonary valve replacement. We sought to determine if pulmonary stenosis patients referred for pulmonary valve replacement were at greater risk for morbidity or need for tricuspid valve intervention at the time of pulmonary valve replacement. A retrospective cohort study was performed on all adult patients with a diagnosis of pulmonary stenosis or tetralogy of Fallot followed at our centre. Clinical and imaging-based exposures were collected. Pre-specified endpoints included need for concomitant tricuspid valve repair or replacement and pre- and post-pulmonary valve replacement cardiac magnetic resonance-based volumetric measurements. Between 1/1999 and 1/2020, 235 patients underwent pulmonary valve replacement for pulmonary regurgitation (52 with pulmonary stenosis, 183 with tetralogy of Fallot). Pulmonary stenosis patients were more likely to have at least moderate tricuspid regurgitation (p = 0.010), undergo concomitant tricuspid valve intervention (p = 0.003), and require tricuspid valve repair or replacement secondary to annular dilation (p = 0.027) compared to tetralogy of Fallot patients. There was no difference in pre-pulmonary valve replacement right ventricular size between pulmonary stenosis and tetralogy of Fallot patients. These findings suggest that referral for pulmonary valve replacement may be occurring later in the disease course for pulmonary stenosis patients.