Congenital Pulmonary Stenosis Research Articles

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.

A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations.

Structural variants (SVs) pose a challenge to detect and interpret, but their study provides novel biological insights and molecular diagnosis underlying rare diseases. The aim of this study was to resolve a 9p24 rearrangement segregating in a family through five generations with a congenital heart defect (congenital pulmonary and aortic valvular stenosis and pulmonary artery stenosis), by applying a combined genomic analysis. The analysis involved multiple techniques, including karyotype, chromosomal microarray analysis (CMA), FISH, genome sequencing (GS), RNA-seq, and optical genome mapping (OGM). A complex 9p24 SV was hinted at by CMA results, showing three interspersed duplicated segments. Combined GS and OGM analyses revealed that the 9p24 duplications constitute a complex SV, on which a set of breakpoints matches the boundaries of the CMA duplicated sequences. The proposed structure for this complex rearrangement implies three duplications associated with an inversion of ~ 2Mb region on chromosome 9 and a SINE element insertion at the more distal breakpoint. Interestingly, this genomic structure of rearrangement forms a chimeric transcript of the KANK1/DMRT1 loci, which was confirmed by both RNA-seq and Sanger sequencing on blood samples from 9p24 rearrangement carriers. Altogether with breakpoint amplification and FISH analysis, this combined approach allowed a deep characterization of this complex rearrangement. Although the genotype-phenotype correlation remains elusive from the molecular mechanism point of view, this study identified a large genomic rearrangement at 9p24 segregating with a familial congenital heart defect, revealing a genetic biomarker that was successfully applied for embryo selection, changing the reproductive perspective of affected individuals.

Enormous Enlargement of Right Atrium Occurred Late After Surgical Dilation of Pulmonary Valve Stenosis: Case Report.

Congenital pulmonary valve stenosis is a relatively common congenital defect, often related to abnormal development and fusion of pulmonary valves. Critical pulmonary valve stenosis should be treated, early in life, before dilation of right chambers, and occurrence of arrhythmias. We report one case of enormous enlargement of right atrium revealed by typical atrial flutter which occurred very late, in 48-year-old man, who underwent surgical dilation of pulmonary valve stenosis at eleven years old, but without repairing dilated tricuspid annulus. Despite successfully ablation of atrial flutter in our cathlab, the patient developed atrial fibrillation, because of an enormous enlargement of right atrium and massive tricuspid regurgitation.

Abstract 15800: Evaluating the Correlation Between Right Ventricular Outflow Tract Dimensions and Arrhythmia Risk Following Self-Expanding Transcatheter Pulmonary Valve Replacement

Introduction: The introduction of self-expanding valves has allowed for an expanded range of patients who can be treated with transcutaneous pulmonary valve replacement (TPVR). Though major complications are rare, ventricular tachycardia has been reported following self-expanding valve placement prompting investigation of potential risk factors. Hypothesis: Significant variation in valve dimensions within the right ventricular outflow tract (RVOT) throughout the cardiac cycle is postulated as a cause for increased arrhythmia risk. We hypothesized that greater dynamic variation of the valve in the RVOT correlates to higher ventricular arrythmia risk. Methods: A single center review was performed of patients who underwent TPVR with either Harmony TPV or Alterra Pre-stent with subsequent placement of 29mm Sapien valve between 2019 and 2023. Using post-procedural 3D rotational angiography, minimum (systole) and maximum (diastole) diameters (mm), perimeter (mm) and cross-sectional area (mm 2 ) of the valve frame were measured in two locations: closest to the branch pulmonary artery bifurcation and the RV cavity. Results: Twenty-eight patients were included (14 Harmony TPV, 14 Alterra). Higher frequency of ventricular arrythmia was seen in patients with congenital pulmonary stenosis ( p =0.004). Higher ventricular arrythmia rate was associated with larger diastolic diameter (34.1 vs 33.2mm, p =0.04), mean perimeter (118.3 vs 108.6mm, p =0.03) and area (1124.5 vs 926.2mm 2 , p =0.03) of the valve frame closest to the RV cavity. Conclusions: Increased movement of the valve frame close to the RV cavity may correlate with a higher ventricular arrythmia risk due to increased contact with the native RVOT throughout the cardiac cycle. Future studies should focus on more accurate, mathematical methodology to better understand whether the complex interaction between self-expanding valves and the native RVOT is a determinant for post-procedural ventricular arrythmia.

Abstract 13652: Machine Learning Prediction of RV End-Diastolic Volume in Patients With Pulmonary Regurgitation

Introduction: RV end-diastolic volume (RVEDV) by cardiac MRI (cMRI) guides intervention in congenital heart disease. Guideline directed linear and area measurements from two-dimensional echocardiography (2DE) have poor univariable linear correlation with RVEDV. We hypothesized that non-linear modeling of 2DE RV measurements may predict cMRI volume. Aims: We sought to develop a prediction algorithm for RVEDV from guideline-directed RV 2DE measurements. Methods: Patients from 2009 to 2022 with > mild pulmonary regurgitation and cMRI +/- 3 months were included. 2DE measurements were: RV end-diastolic (RVED) apical 4-chamber area, basal RVED diameter (d), mid RVED d, tricuspid annulus d, RVED length; PSLAX proximal RVOT d; PSSAX proximal RVOT d, distal RVOT d. A gradient-boosting decision trees algorithm (XGBoost) regressed cMRI RVEDV (mL) using 2DE inputs (including missing data) with leave-one-out crossvalidation. Predicted RVEDV was BSA-indexed to examine performance at clinical threshold 150 mL/m 2 . Intraclass correlation coefficient (ICC) in 30 samples was measured. Results: Of 243 subjects (median age 21 [IQR 16-31] y, 58% tetralogy of Fallot, 22% congenital pulmonary stenosis s/p intervention), 19% had cMRI RVEDV > 150 mL/m 2 . Missing ranged from 5% (basal RVED d) to 17% (PSSA proximal RVOT), and ICC ranged from 0.46 (basal RVED d) to 0.78 (tricuspid annulus). Mean absolute error was 40 mL (27 mL/m 2 ). At the predicted threshold 150 mL/m 2 had 39% sensitivity, 87% specificity, 40% positive predictive value, and 86% negative predictive value for true RV dilation. Conclusion: Prediction of RVEDV from guideline recommended 2DE RV measurements is possible. Detection of clinically significant RV dilation has low sensitivity but may be helpful in ruling out cases. Sources of error include interrater variability and missing data due to poor visualization of the RV on 2DE. Future work to develop a consistent and informative feature set for modeling is required.

Prenatal diagnosis of genetic aberrations in fetuses with pulmonary stenosis in southern China: a retrospective analysis

BackgroundThe genetic etiology of congenital pulmonary stenosis (PS) in fetuses remains inadequately studied. We used karyotype analysis and chromosomal microarray analysis (CMA) to investigate the genetic aberrations associated with PS in human fetuses.MethodsA retrospective analysis was performed on 84 fetuses with congenital PS in southern China. Fetal amniotic fluid and umbilical cord blood samples were obtained for chromosomal karyotype analysis and CMA.ResultsThe rate of pathogenic copy number variation (CNV) was 15.5% (13/84) after karyotyping and CMA. An abnormal karyotype was detected in five cases (6.0%, 5/84) via karyotyping, whereas pathogenic CNVs were detected in 13 cases (15.5%, 13/84) via CMA. In addition to the five abnormal karyotypes detected using karyotype analysis, eight additional chromosomal microduplications and microdeletions were detected using CMA, comprising three cases of 22q11.21 microdeletion; two cases of 16p11.2 microdeletion; one case of simultaneous 18q23 microdeletion and 22q13.33 microduplication; one case of 15q24.1q24.2 microdeletion; and one case of 1q21.1q21.2 microduplication. The rate of pathogenic CNV occurrence was 11.5% in fetuses with isolated PS and 17.2% in fetuses with PS combined with other ultrasound abnormalities. This difference between the two experimental groups was statistically significant. Among 84 fetuses with PS, 39 pregnancies were terminated, and five were lost to follow-up.ConclusionsCMA was not only conducive to detect PS-related pathogenic genomic abnormalities but also to accurately evaluate fetal prognosis in genetic counseling. The early detection of PS and genomic abnormalities will exerta positive impact on fetal intervention and the related prognosis of PS in perinatal infants.

Effect of ketamine versus sevoflurane on the right ventricular pressure during balloon dilatation of congenital pulmonary valve stenosis

Background & Objective: Congenital pulmonary stenosis (PS) is a prevalent cardiac anomaly that is commonly treated with balloon dilatation. The procedure can be successfully completed under appropriate anesthetic technique, depending upon the choice of the anesthetist and the patients’ physical status. We compared the effect of IV ketamine with sevoflurane inhalational anesthesia on right ventricular pressure in infants undergoing balloon dilatation for congenital pulmonary valve stenosis.
 Methodology: This double-blinded, randomized, clinical trial included 40 infants, aged from 1 to 12 months, with congenital PS undergoing balloon dilatation. They were randomly allocated to one of the two groups. In the ketamine group, 20 patients received 2 mg/kg of ketamine intravenously till being unconscious. In the sevoflurane group, 20 patients received 3% sevoflurane and were maintained using the open circuit technique till losing consciousness. The right ventricular pressure was the primary outcome. Secondary outcomes were the hemodynamics and oxygen saturation.
 Results: Compared to sevoflurane, ketamine showed a non-significant difference in the right ventricular pressure before and after induction of anesthesia and after balloon dilatation. The mean arterial blood pressure significantly dropped immediately after sevoflurane induction and after the initial 10 min (P = 0.031 and 0.041, respectively). The heart rate significantly decreased immediately after sevoflurane induction (P = 0.028). The oxygen saturation remained comparable in both groups at 10 and 20 min after induction, and at postoperative anesthesia care unit.
 Conclusion: Intravenous ketamine is considered a safe and effective alternative to sevoflurane for infants with congenital pulmonary stenosis undergoing balloon dilatation. It maintains the right ventricular pressure with stable hemodynamic effects, compared to sevoflurane inhalational anesthesia.
 Abbreviations: PS - Pulmonary Stenosis; TS – Tricuspid Stenosis; PACU – Post Anesthesia Care Unit; TTE - Transthoracic Echocardiography
 Key words: Balloon Dilatation; Infants; Ketamine; Pulmonary Stenosis; Sevoflurane.
 Citation: Sayed AG, Abd el Moez WA, Shoukry A, Elshafeey AE. Effect of ketamine versus sevoflurane on the right ventricular pressure during balloon dilatation of congenital pulmonary valve stenosis. Anaesth. pain intensive care 2023;27(5):451−457; DOI: 10.35975/apic.v27i5.2210
 Received: April 18, 2023; Reviewed: July 18, 2023; Accepted: August 21, 2023

D-7 | Outcomes of Patent Ductus Arteriosus Therapies in Patients

Presence of a hemodynamically significant PDA in premature infants, especially in <29 weeks is associated with complications like prolonged mechanical ventilation, NEC and IVH. Therapy with IV acetaminophen or NSAIDs for closure is effective in <50% and associated with many complications. Transcatheter PDA closure (TCPC) including Piccolo device approved for infants >700g has shown >95% success without significant complications. There is a lot of practice variability with no management consensus. We compared the outcomes between medical, surgical and device closure in patients of <2000g, including complications. Retrospective review of infants <29 week gestation, who underwent medical/interventional/surgical PDA closure at <2Kg at Nicklaus Children’s Hospital from 1/2010-11/2022. Patients with complex congenital heart defects, coarctation or pulmonary artery stenosis were excluded. TCPC device complications assessed included TV regurgitation, significant LPA or aortic obstruction, device embolization or erosion. Respiratory status calculated as respiratory severity score was also compared. Total of 86 infants born <29 weeks gestation and <2000g at procedure were included. 56% patients failed primary medical therapy and required either TCPC or surgical therapy (43% vs 57%). Medication use was associated with complications including NEC, pulmonary hemorrhage and AKI in 24% patients (n=15). The median gestational age of patients undergoing TCPC was 25+1 (22-28) wks, median weight 1260g (790-1930g), similar to surgical group for gestation and weight (1040g, 600-2000). 36 patients underwent TCPC with Piccolo, the remainder with MVP. Neonates with TCPC showed earlier improvement in respiratory status (RSS 3.6 vs 4.5, p 0.037 ) and earlier extubation (10 days vs. 26 days, p 0.01) compared to surgical ligation. TCPC use was safe and with no significant LPA or aortic stenosis seen with Piccolo device, one with MVP. Moderate TR was seen in one patient following Piccolo device. New NEC was seen in 1 patient after 10 days. TCPC is effective in patients <2000g with earlier improvement in respiratory status compared to surgical ligation, without any significant complications.

Alternative Approach for Pulmonary Valvuloplasty in Critical Congenital Pulmonary Stenosis

Critical congenital pulmonary stenosis with intact interventricular septum is a cyanotic and potentially lethal neonatal cardiac anomaly. Percutaneous transcatheter balloon pulmonary valvuloplasty for critical pulmonary stenosis often presents technical difficulties due to supra-systemic pressure in right ventricle. Using transjugular approach instead of the femoral vein helps in dealing with this issue. We describe the successful use of right internal jugular vein approach in a case of critical pulmonary stenosis.

Role of left atrial hypertension in pulmonary hypertension associated with bronchopulmonary dysplasia.

Left atrial hypertension (LAH) may contribute to pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD). Primary causes of LAH in infants with BPD include left ventricular diastolic dysfunction or hemodynamically significant left to right shunt. The incidence of LAH, which is definitively diagnosed by cardiac catheterization, and its contribution to PH is unknown in patients with BPD-PH. We report the prevalence of LAH in an institutional cohort with BPD-PH with careful examination of hemodynamic contributors and impact on patient outcomes. This single-center, retrospective cohort study examined children <2 years of age with BPD-PH who underwent cardiac catheterization at Lucile Packard Children's Hospital Stanford. Patients with unrepaired simple shunt congenital heart disease (CHD) and pulmonary vein stenosis (only 1 or 2 vessel disease) were included. Patients with complex CHD were excluded. From April 2010 to December 2021, 34 patients with BPD-PH underwent cardiac catheterization. We define LAH as pulmonary capillary wedge pressure (PCWP) or left atrial pressure (LAP) of at least 10 mmHg. In this cohort, median PCWP was 8 mmHg, with LAH present in 32% (n = 11) of the total cohort. A majority (88%, n = 30) of the cohort had severe BPD. Most patients had some form of underlying CHD and/or pulmonary vein stenosis: 62% (n = 21) with an atrial septal defect or patent foramen ovale, 62% (n = 21) with patent ductus arteriosus, 12% (n = 4) with ventricular septal defect, and 12% (n = 4) with pulmonary vein stenosis. Using an unadjusted logistic regression model, baseline requirement for positive pressure ventilation at time of cardiac catheterization was associated with increased risk for LAH (odds ratio 8.44, 95% CI 1.46–48.85, p = 0.02). Small for gestational age birthweight, sildenafil use, and CHD were not associated with increased risk for LAH. LAH was associated with increased risk for the composite outcome of tracheostomy and/or death, with a hazard ratio of 6.32 (95% CI 1.72, 22.96; p = 0.005). While the etiology of BPD-PH is multifactorial, LAH is associated with PH in some cases and may play a role in clinical management and patient outcomes.

Long-term results of balloon pulmonary valvuloplasty in pediatric age group in surgical specialty teaching hospital/cardiac center/Hawler

Congenital valvular pulmonary stenosis accounts for 5-10% of all congenital heart disease. Balloon pulmonary valvuloplasty is a safe and effective method in reduction of moderate to severe valvular pulmonary stenosis. This retrospective study done in Hawler surgical specialty cardiac center on pediatric patients who had pulmonary valve stenosis (with echocardiographic peak gradient 2:50mmHg) and treated by balloon pulmonary valvuloplasty. A total of 178 cases were involved, 93(52.25%) patient was male and 85 (47.75%) patients was female. 160 patient (89.89%) were treated with single balloon method 18 patient (10.11%) were managed by double balloon method technique. Follow up period of these patients range from 1 year to 10 years (mean of 5.5 year). In 153 patients (85.96%) pressure across pulmonary valve were below 36 mm Hg, while in 21 (11.80%) pressure gradient across pulmonary valve were (36-50 mm Hg). Four (2.24%) patients had pressure gradient across pulmonary valve more than 50 mm Hg. Forty patients (22.47%) developed mild pulmonary valve regurgitation, while 20 patient (11.24%) developed significant pulmonary valve regurgitation. Balloon pulmonary valvuloplasty provides long-term relief of pulmonary valvular obstruction in the majority of pediatric patients. The long-term results are favorable.

B-35 | Comparison of Premounted Drug Eluting Stents vs. Non-Eluting Stents for the Treatment of Pulmonary Artery Stenosis In Smaller Patients

Small patients with congenital or post-operative pulmonary artery stenosis (PAS) often require multiple catheterizations. Frequently, balloon angioplasty results in only temporary improvement and occasionally, stenting is necessary. Pre-mounted stents have a low profile and are easier to advance in this population, and recent evidence has shown some of these stents can be fractured longitudinally with high pressure balloons allowing for further growth potential. However, restenosis is common in bare metal stents.

Right ventricular outflow tract anomalies: Neonatal interventions and outcomes

Right ventricular outflow tract (RVOT) anomalies comprise a wide spectrum of congenital heart disease, typically characterized by obstruction to flow from the right ventricle to pulmonary arteries. This review highlights important considerations surrounding management strategy as well as clinical outcomes for the neonate with RVOT anomaly, including: pulmonary atresia with intact ventricular septum, congenital pulmonary valve stenosis, tetralogy of Fallot, and Ebstein anomaly with anatomic or physiologic RVOT obstruction.

COMBINED SEVERE AORTIC AND PULMONARY VALVULAR STENOSIS IN A CHILD AND ITS MANAGEMENT: A CASE REPORT

Combined congenital aortic and pulmonary valvular stenosis is a rare congenital heart defect. Prevalence of severe combined valvular stenosis of aortic and pulmonary valve accounts about 0.01% and also has association with many syndromes. This combination presents unusual diagnostic as well as management problems. Apart from a few case reports, there is little in the literature on the combined stenosis of both semilunar valves and its management. We present this rare combination in a 9 year old boy which was promptly managed with the balloon valvoplasty without any complications in the same setting under local anesthesia with sedation.

Short-term results of sutureless closure for primary total anomalous pulmonary venous connection: seventeen cases

Total anomalous pulmonary venous connection (TAPVC) is a rare condition. Mortality of TAPVC has improved dramatically in the present. Sutureless closure had initially used for congenital pulmonary venous stenosis (PVS) or post-repair PVS. Recently, it had been adopted for primary TAPVC to prevent postoperative pulmonary venous obstruction, a leading cause of death. This technique had gradually applied at our institute for primary TAPVC since 2018. Prospective case series was conducted from mid-2019. Including criteria consists of patients with primary TAPVC. These are all supracardiac, infracardiac, mixed type and intracardiac TAPVC with pulmonary venous stenosis. Excluding measures are TAPVC with single ventricle, isomerism or heterotaxy. End-point outcomes were mortality and short-term PVS. Seventeen TAPVC cases were enrolled in this study from 06/2019-12/2020 at Children’s Hospital 1. Male/female ratio was 12/5. Median age at admission was 44 (3-1010) days old. The median operative weight was 3.9 kg (2.4-11). Of those, fourteen (82.4%) cases were supracardiac TAPVC and 3 (17.6%) cases were infracardiac TAPVC. Nine (52.9%) cases were emergency operations. Median aortic clamp time was 66 (32-138) mins. Median bypass time was 112 (86-212) mins. There were 9 (52.9%) cases with arrhythmias, 2 (11.8%) cases with chylothorax. Mean ventilation time was 3.6±0.5 days; mean CICU time was 6.5 (1-20), median LOS was 14.5 (8-39). In-hospital mortality was 5.9% (1). Mean follow-up time was 12.3±6.4 months (range 4-24), there was no PVS with median pulmonary venous score of 0 (range 0-1). Sutureless technique could be a safe option for primary TAPVC repair.

Role of Balloon Pulmonary Valvuloplasty in the Management of Pulmonary Stenosis

Although there is definitive evidence for pressure gradient relief both immediately after and at follow-up after balloon pulmonary valvuloplasty (BPV) for pulmonary stenosis (PS), the progression of pulmonary insufficiency (PI) at late follow up emerged as a concern. To address the concern for development of PI during late follow-up, balloon/annuls ratio used for BPV was reduced to 1.2 to 1.25. Recurrence of stenosis was seen in nearly 10% of patients. The causes of recurrence were identified to be balloon/annulus ratio less than 1.2 and immediate post-BPV gradients in excess of 30 mmHg. Recurrent obstructions can be effectively relieved by repeat BPV. The BPV procedure is safe and effective in fetal, neonatal and adult subjects as well. The BPV is also effective in palliating cyanotic congenital heart disease patients with valvar PS. Despite the limitations, BPV is currently considered as therapeutic procedure of choice in the management of congenital PS in both the pediatric and adult populations. BPV provides an excellent alternative to surgical intervention and has become the preferred intervention for initial treatment for PS in neonates, infants, children, adolescents, and adults. Careful follow-up to detect development of significant PI and investigate methods to prevent PI are recommended.

Congenital pulmonary vein stenosis and bronchopulmonary vascular malformation

ResumenEl objetivo es mostrar el diagnóstico y la evolución de una paciente con estenosis de venas pulmonares y secuestro pulmonar. Se trata de una niña de 1 año de edad, con bronconeumonías de repetición, acrocianosis, 2R intenso, cardiomegalia, hipertensión venocapilar pulmonar, con diagnóstico clínico de comunicación interauricular. El ecocardiograma mostró estenosis de venas pulmonares izquierdas. El cateterismo cardiaco detectó fístulas arteriovenosas en la región apical del pulmón derecho. La imagen de resonancia magnética y la angiografía mostraron un vaso arterial aberrante paralelo a la aorta abdominal y con flujo dirigido al lóbulo pulmonar derecho. La angiotomografía reportó confluencia de las venas pulmonares del lado derecho. Se realizó lobectomía derecha. La paciente falleció en el posoperatorio debido a una hemorragia masiva pulmonar. Esta paciente es la primera descrita en la literatura con estenosis de venas pulmonares congénita asociada a secuestro pulmonar. La ecocardiografía es el estudio diagnóstico ideal inicial en los pacientes con estenosis congénita de venas pulmonares.

Is there any relationship between biomarkers and echocardiographic markers in patients with pulmonary stenosis underwent balloon valvuloplasty?

Congenital pulmonary stenosis (PS) is a progressive disease. Balloon pulmonary valvuloplasty (BPV) is the treatment of choice in valvular PS. We aim to study the relationship between biomarkers and echocardiographic markers in valvular PS and to assess the impact of BPV on these markers. Patients with moderate and severe valvular PS amenable for BPV were recruited. Serum troponin I was measured. Echocardiographic assessment of PS and right ventricular (RV) function was done. All patients underwent BPV. Troponin level and echocardiographic data were re-assessed 2weeks and 6months after BPV. Fifty patients with valvular PS were recruited. There was significant correlation between peak SPG and troponin (P<.001). Troponin was significantly decreased 2weeks after BPV. Similarly, there was an initial improvement in RV function. After 6months of follow-up, we divided patients into two groups: Group A: 36 patients with no restenosis. Group B: 14 patients with restenosis. There were high significant differences between both groups regarding troponin level and RV functions with re-elevated troponin in Group B that correlated with peak PG (r=.9, P<.001). RV function parameters in Group B became significantly worse 6months after BPV than those after the initial 2weeks. Troponin correlates with the severity of PS and associates with RV dysfunction. Both troponin and RV functions improved with BPV. Recurrent elevation of troponin and impairment of RV function is associated with PV restenosis and could be set as an indication for repeated balloon dilatation of PV.

Diet-Responsive Hypercholesterolemia With Cardiofaciocutaneous Syndrome Type 3

Background: Molecular basis of diet responsive hypercholesterolemia remains unclear. We report diet-responsive severe hypercholesterolemia in a young female with cardiofaciocutaneous syndrome type 3 (CFC3) due to a heterozygous pathogenic MAP2K1 variant, suggesting a role of common MAPK variants in LDL-cholesterol (LDL-C) response to diet. Clinical case: A 3-year-old Caucasian female with CFC3 (macrocephaly, frontal bossing, wide nasal root with depressed bridge, anteverted nares, low set fleshy ears, congenital pulmonic valve stenosis, postnatal growth deficiency, hypotonia, and neurocognitive impairment) due to a de novo heterozygous c.389A>G, p.Tyr130Cys pathogenic variant in MAP2K1, presented with extremely elevated serum total cholesterol of 446 mg/dL, triglycerides of 239 mg/dL, HDL-cholesterol of 53 mg/dL, LDL-C of 335 mg/dL (normal range < 110 mg/dL) and serum apolipoprotein B level 219 mg/dL (normal range < 90 mg/dL). Her LDL-C was 252 mg/dL a year ago and 215 mg/dL one month prior to presentation. Reducing total dietary fat to 20–25% of total energy and saturated fat to <6% of total energy over the next 4 months lowered LDL-C to 104 mg/dL. However, her weight decreased by 0.5 kg and liberalization of fat intake again increased LDL-C to 222 mg/dL. Her father has mildly elevated LDL-C of 160 mg/dL and her mother had normal LDL-C of 80 mg/dL. Her plasma phytosterol levels were normal and she had ApoE3/E3 genotype. Targeted genetic testing of the patient and parents showed a benign heterozygous LDL receptor (LDLR) variant c.2242G>A; p.Asp748Asn, (Minor allele frequency 0.00008) in the patient and her father. Whole exome sequencing of the patient and both parents showed no known disease-causing variants in LDLR, APOB, PCSK9, LDLRAP1, APOE, STAP1, LIPA, ABCG5, ABCG8 and other known hyperlipidemia-related genes. There are no previous reports of hypercholesterolemia in patients with CFC3. MAP2K1 stimulates various MAP kinases upon wide variety of extra- and intracellular signal and is involved in cell proliferation, differentiation, transcription regulation and development. Previous studies of the relationship between p42/44MAPK activation and LDLR expression in human hepatoma HepG2-derived cell line showed that that activation of the Raf-1/MEK/p42/44MAPK cascade induces LDLR expression and modulation of the Raf-1 kinase signal strength can determine LDLR expression levels. Thus, extent of MAPK activation can alter signaling of LDLR, resulting in hypercholesterolemia. Conclusion: Our case report suggests that MAP2K1 may play a significant role in LDLR signaling, and some MAP2K1 variants may be associated with diet-responsive hypercholesterolemia. Larger studies are required to assess dietary response to LDL-C in subjects with MAP2K1 variants.

Interposition Technique for Pulmonary Valve Replacement.

Stented bioprosthesis implant at surgical pulmonary valve replacement (PVR) ideally should be 25 to 27 mm to facilitate future percutaneous PVR. This often requires accommodating 35 to 37 mm diameter sewing ring in the pulmonary position and requires anterior patch augmentation of the right ventricular outflow tract (RVOT). We present a novel "interposition" technique of PVR that allows upsizing the valve without RVOT patch augmentation. Using standard cardiopulmonary bypass, the main pulmonary artery (MPA) is dissected and transected at an appropriate level. The remnants of pulmonary valve leaflets are excised. The valve stent posts are telescoped into distal MPA, the MPA continuity is restored by end-to-end anastomosis of the proximal and distal MPA, with the interposed prosthetic valve sewing ring in the suture line between the two edges of the MPA with the bulk of the sewing ring extravascular. A total of seven patients (tetralogy of Fallot, three; congenital pulmonary stenosis, four; age range: 15-33 years) underwent the procedure. No patient required RVOT patch augmentation, all patients were extubated in the operating room and were fast-tracked to recovery. Our proposed technique of PVR has the following advantages: accommodate larger size valve, eliminates risk of a paravalvar leak, coronary compression, and anterior tilting of the prosthesis. The valve interposition technique avoids the need for RVOT patch, allows implantation of an adequate sized prosthetic valve, maintains native geometry of the pulmonary artery without the risk of tilting of the prosthesis, and eliminates the risk of paravalvular regurgitation and left coronary compression.