Williams syndrome is a rare congenital disorder affecting connective tissue and the cardiovascular and central nervous systems. Pediatric patients diagnosed with Williams syndrome face significant risk for cardiac collapse and death when undergoing anesthesia. We sought to evaluate our institution's historical practices, evaluate individual risk stratification, and create detailed standardized perianesthesia guidelines for management of this population, particularly during noncardiac procedures. The study included a retrospective chart review of pediatric patients with Williams syndrome who received anesthesia over a 10-year period at a single institution. A total of 23 patients underwent 46 procedures. At time of procedure, median age was 5.8 years (range, 0.4-17.6 yr), and the majority (n = 19) had a "low" Williams syndrome risk category and required anesthesia for noncardiac procedures. Most (61%) had no cardiac involvement beyond mild supravalvar or branch pulmonary artery stenosis. No intraprocedure adverse cardiac events were identified. One patient experienced an adverse cardiac event approximately 60 minutes postanesthesia emergence which included ST segment depression and development of refractory ventricular fibrillation, necessitating deployment of venoarterial extracorporeal membrane oxygenation. This patient was eventually stabilized and was taken to the operating room 3 days later for definitive severe supravalvar aortic stenosis repair. Patients with Williams syndrome have a reported risk for sudden cardiac death that is 25 to 100 times greater than that of the age-matched general population. The incidence of adverse cardiac events in our cohort of patients with Williams syndrome undergoing anesthesia was lower compared with previous studies, which reported rates ranging from 4.2% to 11%. These findings support the idea that risk stratification and institutional practice guidelines can aid anesthesia providers in making informed decisions, and standardization of pre-, intra-, and postprocedural care according to existing guidelines may further reduce risks. Our review offers valuable insight into historical anesthesia management and contributes to a broader interdisciplinary understanding of care provision for this high-risk group.

Management of supravalvular aortic stenosis with the Doty technique, in a South American pediatric center

Immigration is a social determinant of health that can be divided into the time-based categories of premigration, during-migration and postmigration. Latino immigrants face numerous threats to their health during each phase of the migration journey, such as premigration violence, hazardous conditions during migration and postmigration discrimination. This is a report of a child who fled violence to seek asylum in the USA and was subsequently diagnosed with supravalvular aortic stenosis, which required cardiac surgery repair. The case analysis uncovers challenges and facilitators to health for immigrants with barriers to documentation at policy, organisational and interpersonal levels and makes suggestions to advance health equity in the USA. The exclusion of immigrants with barriers to documentation from healthcare, uneven distribution of charity care, inadequate language services and provider biases are among the key issues addressed.

Toward a rational therapeutic for elastin related disease: Key considerations for elastin based regenerative medicine strategies.

Supravalvular aortic stenosis caused by compression of a pseudoaneurysm late after aortic root replacement.

Introduction: Elastin is the major component of elastic lamellae that alternate with smooth muscle cells (SMCs) to form lamellar units in arteries. In humans, heterozygous loss-of-function mutations in the elastin gene ELN cause supravalvular aortic stenosis (SVAS), which is characterized by aortic SMC accumulation and subsequent lumen obstruction. Defective elastic lamellae and excess SMC accumulation are also observed during physiological closure of the ductus arteriosus (DA). Failure of DA closure (i.e., patent DA [PDA]) leads to improper blood flow distribution and subsequent mortality. SMC accumulation is essential for DA closure. Thus, promoting SMC proliferation may be therapeutic for PDA, while SMC accumulation is detrimental for patients with SVAS and some congenital heart diseases in which PDA maintains pulmonary or systematic circulation. Although controlling SMC accumulation is desired in these elastin-defective arteries, mechanistic links between defective elastin and SMC hyperproliferation in SVAS and DA are not well elucidated. Methods: Because elastin is expressed in the mouse aorta from embryonic day (E) 14, immunostaining for smooth muscle actin and proliferation marker Ki67 was performed on wild-type (WT) and Eln(-/-) mouse aortas at E13.5, E15.5, and postnatal day (P) 0.5. Bulk RNA-seq was conducted on mouse aortic SMCs isolated from WT or Eln(-/-) embryos at E15.5. As sphingosine kinase 1 (SPHK1) was found as a highly promising candidate, its expression was evaluated in human SVAS patient aortas and in mouse Eln(-/-) aortas and WT DA. Sphingosine-1-phosphate receptor 1 (S1PR1) activity was assessed in aortic SMCs from S1pr1(knock-in/knock-in), H2B-GFP mice. Genetic deletion of Sphk1 in SMCs was performed on the elastin mutant background. Pharmacological SPHK1 inhibition was evaluated on both elastin mutants and WT embryos. Regulatory mechanisms of SPHK1 were assessed by mRNA stability assay and TRANSFAC database analysis. Results: Aortic hypermuscularization and stenosis are observed in Eln(-/-) mice at P0.5 but not at E13.5 and E15.5. SMC hyperproliferation is initially observed in Eln(-/-) aorta from E15.5. Bulk RNA-seq revealed that Sphk1 is the most upregulated transcript in Eln(-/-) aortic SMCs at E15.5. Reduced ELN increases SPHK1 levels in SMCs of human patient aortas and mouse aorta and DA. S1PR1 expression and activity are increased by elastin insufficiency. SMC Sphk1 deletion attenuates SMC proliferation and muscularization in the elastin-defective aorta, leading to extended viability of Eln(-/-) mice. Similarly, pharmacological SPHK1 inhibition ameliorates elastin aortopathy but leads to PDA in WT mice. mRNA stability assay indicated Sphk1 is upregulated by enhanced transcription. TRANSFAC and bulk RNA-seq data suggested that transcription factor early growth response 1 (Egr1) induces Sphk1 transcription. Indeed, EGR1 was upregulated in elastin mutant aortas and WT DA. Conclusions: Elastin deficiency upregulates SPHK1 transcription, resulting in SMC hyperproliferation and muscularization in pathological SVAS and physiological DA closure. Consistent data across different arteries in distinct contexts emphasizes the importance of SPHK1-mediated signaling, suggesting a broader relevance in vascular development, homeostasis, and disease. AHA (19EIA34660321, 23CSA1051139 to D.M.G.), AHA/CHF (23POSTCHF1022933 to J.S.), NIH (K99HL171838 to J.S., R35HL150766, R01HL142674, R21NS123469 to D.M.G.). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Supravalvular aortic stenosis (SVAS) is an autosomal dominantly inherited congenital cardiovascular disease caused by disruption of elastin gene (ELN), encoding elastin, an essential component of elastic arteries. It usually affects the middle layer of the wall of the aorta but also the pulmonary and coronary arteries may be affected. We report a family with six affected siblings who were closely followed up from infancy to early adulthood at a pediatric cardiology outpatient clinic. Whole-exome sequencing was performed using DNA of the index patient. Targeted variant testing was performed for other family members. The affected siblings presented with a wide spectrum of clinical features of SVAS, ranging from mild pulmonary artery stenosis with or without pulmonary artery branch stenoses to severe supravalvular aortic obstruction and coronary artery stenosis with fatal outcome. Genetic analysis identified a novel pathogenic 1-bp deletion c.1983delG, p. (Pro662Leufs*13) in the ELN gene. Males tended to have a more severe cardiac disease than females. However, if interventions were successful during infancy or early childhood, the outcome was fairly favorable. Moreover, supravalvular pulmonary stenosis, even when combined with a stenotic pulmonary valve and severe pulmonary artery branch stenoses, tended to resolve during follow-up. We describe a family with six siblings showing elastin arteriopathy with variable disease severity and outcome. A novel pathogenic ELN gene variant was detected in five of them, indicating that there are obviously yet unknown genetic and environmental modifying factors that affect the severity and outcome in individual patients.

Background: Pediatric renovascular hypertension (PRVH), a rare disorder (1 in 1.9 million annually), is marked by renal artery narrowing and abdominal aortic coarctation, leading to renin-mediated hypertension. Its genetic basis is only partially explained by genetic syndromes, including Williams Syndrome (WS), which features supravalvular aortic stenosis (SVAS) and other vascular abnormalities. The ELN gene on chromosome 7q11.23 encodes elastin, an essential vascular connective tissue protein. ELN deletions are known to be linked to aortic stiffness and narrowing. Whether ELN gene variation is specifically associated with PRVH and whether copy number variation (CNV) or partial deletions of ELN underlie PRVH in individuals without a genetic syndrome is unknown. Methods: Genotype intensities were analyzed using Illumina BeadArray v1.1, comprising 607,780 SNP probes with a median inter-SNP spacing of approximately 3 kb. The study compared 111 University of Michigan PRVH cases to 1,853 controls from the Michigan Genomic Initiative (1:19 ratio), matched by age, sex, and ancestry by principal components. CNVs were inferred using log R ratio (LRR) and B allele frequency (BAF) with a hidden Markov model. CNVRs were defined as CNV regions with at least 25 consecutive SNPs, merged within 50 Kb gaps, and analyzed for case-control associations using Fisher’s exact test. Results: 627 unique CNVRs were identified, with the strongest PRVH-associated risk signal being a deletion (CN=1) at chr7q11.23 (72722981-74126034, GRCh37/hg19), in 5 PRVH cases and absent in all controls (P=5.29×10 -7 ). Genotype-phenotype analysis confirmed that all 5 individuals carried a clinical diagnosis of WS, and all individuals carrying a diagnosis of WS had 7q11.23 copy loss. ELN was deleted across all exons in all cases, with no evidence of smaller deletions. As genotype-phenotype correlations have been identified for non-cardiovascular manifestations of WS, we noted that in addition to ELN , the additional genes deleted in all five cases were B AZ1B, BCL7B, TBL2, MLXIPL, LIMK1, EIF4H, LAT2, RFC2, CLIP2 , and GTF2IRD1 . Vascular phenotypes showed abdominal aortic narrowing in 4 cases and isolated renal artery stenosis in one child, the latter a previously unappreciated WS vascular lesion. Conclusions: Despite PRVH’s rarity, this study reports a statistically significant association between aortorenal dysplasia causing PRVH and a strongly deleterious genetic lesion of WS involving ELN deletions.

In patients with complex congenital heart disease (CHD) pathogenic SMAD6 variants have been described previously. The aim of this study was to analyze if pathogenic SMAD6 variants also occur in patients with CHD associated with pulmonary arterial hypertension (CHD-APAH) or idiopathic PAH. A PAH gene panel with up to 64 genes including SMAD6 was used to sequence 311 patients with idiopathic PAH (IPAH) and 32 with CHD-APAH. In 4 of 32 (12.5%) CHD-APAH and in 2 out of 311 (0.64%) IPAH patients we identified likely pathogenic or rare SMAD6 missense variants. All CHD-APAH patients with a rare SMAD6 variant had complex CHD. One patient had bi-allelic SMAD6 variants, combined pulmonary valve defect and supravalvular aortic stenosis, craniosynostosis and radioulnar synostosis. This is the first description of potentially disease-causing SMAD6 variants in patients with IPAH and complex CHD-APAH. Further studies are needed to assess pathogenesis and prevalence of pathogenic SMAD6 variants in PAH.

Objective: More attention should be paid to glucose metabolism in children with Williams-Beuren syndrome (WBS). Methods: The clinical data of a child diagnosed with WBS due to diabetic ketoacidosis (DKA) were retrospectively analyzed, and the related literature was reviewed. Results: An 8-year-old boy presented with thickened upper lip, low palatal arch, strong heart sound, rumbling murmur in the apex area, a little pigmentation in the webbed margin of fingers and toes, and atypical elfin features. Blood gas analysis showed severe ketoacidosis with significantly elevated amylase, significantly increased amylase, elevated blood lipids, abnormal thyroid function, negative C-peptide, diabetic. Echocardiography showed supravalvular aortic stenosis and abnormal continental valve. The large copy number variation of the nuclear genome revealed a heterozygous variation in the 7q11.23 region, with a 1.4 Mb deletion in the 7q11.23 region, and the related gene in the region was elastin gene. Conclusion: DKA was reported for the first time as the first symptom of WBS diabetes. The mechanism of concurrent DKA in WBS is not well understood.

Early severe supravalvular aortic stenosis in 16-day-old neonate.

Several techniques for the surgical correction of congenital supravalvular aortic stenosis have been devised. We describe the step-by-step surgical approach of a slide aortoplasty to correct localized supravalvular aortic stenosis in a 3-year-old child with Williams syndrome.

Patients who underwent surgical repair of supravalvular aortic stenosis (SVAS) are at high risk for postoperative major adverse cardiovascular events (MACE). This study aimed to investigate the association between cardiopulmonary bypass (CPB) duration and MACE occurring during postoperative hospitalization or within 30 days post-surgery. Patients who underwent surgical repair of SVAS from 2002 to 2019 at Beijing Fuwai Hospital and Yunnan Fuwai Hospital were included in this study. Patients were stratified into "CPB duration >2 h" and "CPB duration ≤2 h" groups based on intraoperative CPB duration. Various statistical methodologies were employed to investigate the association between CPB duration and early postoperative MACE, including multivariate adjustment, propensity score adjustment, propensity score matching, and logistic regression based on propensity score weighting. 297 participants were included and 164 were finally matched. In the propensity score-matched cohort, CPB duration was positively associated with early postoperative MACE (odds ratio = 18.13; 95% confidence interval 2.33-140.86; P = 0.006). Consistent results were obtained in the Inverse probability of treatment-weighted, standardized mortality ratio-weighted, pairwise algorithmic-weighted, and overlap-weighted models. Patients with CPB duration >2 h were at a higher risk of early postoperative MACE compared to those with CPB duration ≤2 h. This emphasized the significance of minimizing CPB exposure for the prognosis of patients with SVAS.

BackgroundAn effective prognostic nomogram to predict the prognosis for supravalvular aortic stenosis (SVAS) patients is lacking.MethodsA multi-center retrospective study of consecutive SVAS patients with surgery between 2002 and 2020 was conducted. Patients underwent McGoon repairs, Doty repairs, and other repairs. The primary outcome was the re-operation or restenosis at follow-up. The nomogram based on Cox regression and Kaplan–Meier method was used to show the risk factors of the primary outcome. The predictive accuracy was determined by the concordance index (C-index) and calibration curve. The results were validated using the bootstrap resampling method.ResultsOf the 291 SVAS patients, 143 (49.1%) used McGoon repairs, 118 (40.5%) used Doty repairs and 30 (10.3%) used other repairs. The median age at operation was 4.9 years (IQR 2.3–9.9). After a median follow-up of 24 months (IQR 6.0–54.0), no difference in re-operation or restenosis was found between McGoon repairs and Doty repairs. Age, gender, SVAS type, pulmonary artery stenosis, aortic valve stenosis, sinotubular junction z-score and gradient were considered independent risk factors by Lasso regression and were included in the nomogram. The C-index of the nomogram was 0.71 (95% CI 0.61 to 0.81). The calibration curve for the probability of re-operation or restenosis showed good agreement between prediction by nomogram and actual observation.ConclusionsMcGoon repairs and Doty repairs had no difference in re-operation and restenosis risk. The proposed nomogram gave an accurate prediction of re-operation or restenosis for patients with SVAS after surgery.Trial registrationhttp://www.chictr.org.cn, ChiCTR2300067851, 2023.01.29 (retrospectively registered).

Introduction:Conventionally, the surgical approach for Taussig–Bing anomaly (TBA) and transposition of the great arteries with aortic arch obstruction (AAO) has often involved a two-stage strategy. However, in contemporary practice, most centers now favor a one-stage repair. Despite this trend, the choice between one-stage and two-stage strategies may still arise in specific anatomical cases, such as those with interrupted AA (IAA) or in low-weight infants.Patients and Methods:We conducted a review of our institutional experience with single-stage correction in 24 consecutive cases of TBA associated with AAO. Each patient underwent a single-stage correction that included an arterial switch operation (ASO) along with ventricular septal defect (VSD) closure through baffling of the left ventricle to the neo-aorta and AA repair. Early mortality or reoperation was defined as death or the need for reoperation occurring prior to hospital discharge or within 30 days following ASO. Reintervention was classified as either a reoperation or a transcatheter procedure.Results:The study comprised 24 cases. Among them, 6 (25%) patients had TBA with aortic coarctation, 15 (62.5%) patients had TBA with hypoplastic AA (HAA), 2 (8.3%) patients presented with TBA and IAA, and one patient had TBA with HAA alongside partial anomalous pulmonary venous connection. There were two early postoperative deaths (8.3%). Recoarctation occurred in 2 (8.3%) cases, both of which involved TBA with AA hypoplasia. Both patients successfully underwent balloon dilation of the coarctation after 285 and 312 days, respectively. One (4.2%) patient developed subaortic stenosis and underwent a modified Konno procedure after 233 days. The total number of reinterventions was 5 (20.8%), which included three cardiac catheterization procedures (two successful balloon dilations of the coarctation and one unsuccessful balloon dilation of the supravalvular stenosis), along with two surgical reinterventions.Conclusions:The single-stage repair involving VSD closure, AA reconstruction, and ASO is an applicable and safe option for patients with combined TBA and concomitant AAO. We recorded reinterventions for recurrent coarctation, supravalvular, and subvalvular aortic stenosis. Long-term follow-up is essential, and early percutaneous interventions may help lower the rates of repeat surgeries.

Williams syndrome (WS), also known as Williams-Beuren syndrome, is an autosomal dominant disorder. Although the exact incidence is unknown, it is estimated to occur in approximately 1 in 20,000 live births. The syndrome has been identified in all ethnic groups worldwide and affects both sexes equally. Individuals diagnosed with WS have a de novo deletion of 1.5 to 1.8 Mb at 7q11.23, and although rare, an affected parent of a person with WS may also carry this deletion. This syndrome is a multisystem disorder that affects both mental and physical development. The deleted region of chromosome 7q11.23 observed in WS includes the ELN gene, which encodes the elastin protein, a critical component of elastic fibers found in the connective tissue of many organs. WS is characterized by distinctive facial features (elfin-like face), cardiovascular anomalies, primarily supravalvular aortic stenosis (SV AS), growth delay, early puberty, endocrine disorders such as hypothyroidism, intellectual disability with a typical neurobehavioral profile, and often infantile hypercalcemia. Additionally, facial features include a broad forehead, bitemporal narrowing, periorbital fullness, a stellate/lacy iris pattern, strabismus, a short nose with a broad nasal tip, malar flattening, a long philtrum, thick vermilion line of the upper and lower lips, and a wide mouth. The identified intraoral findings of the syndrome include generalized diastemas (70%), a high-arched palate, hypodontia (50%), microdontia, and enamel hypoplasia. Additionally, these patients may present with malocclusion conditions such as small roots, dens invaginatus, anterior crossbite, anterior deep bite, or open bite. Dental malocclusion is present in 85% of individuals with WS and responds to orthodontic treatment. Poor fine motor skills pose challenges in maintaining oral hygiene and increase the risk of dental caries. The aim of this case presentation is to describe the facial, oral, and dental features observed in a pediatric patient with Williams Syndrome and to detail the therapeutic approaches employed.

Phenotypic Findings Associated with Variation in Elastin

ABSTRACTBackgroundSupravalvular aortic stenosis (SVAS) is a rare condition with limited data on patients beyond childhood. This study aims to investigate the clinical course and outcomes of SVAS in adults.MethodsAll adult (≥18 years) patients with SVAS, prospectively registered in the Dutch Congenital Cor Vitia database between 2001 and 2019, were included. Survival and event-free survival were assessed. Evolution of peak velocity was analysed using linear mixed models. Differences in previous operated state, sex and Williams-Beuren syndrome were explored.Results65 patients were included (age: 23 (IQR: 20, 31) years, 31% female, 46% previous SVAS correction, 47% Williams-Beuren syndrome). The peak velocity was 2.3±1.0 m/s at inclusion. Median follow-up time was 13 (IQR: 10, 17) years. Four patients died (one patient after cardiac surgery, two of non-cardiac causes and in one patient the cause of death was unknown) resulting in a 10-year survival of 95% (95% CI 90% to 100%) and event-free survival of 83% (95% CI 74% to 93%). There were no differences in event-free survival between previous operated state (p=0.2), sex (p=0.48) or Williams-Beuren syndrome (p=0.85). 31 cardiovascular events occurred in 15 patients, with the majority being arrhythmias. All SVAS-related interventions (three surgeries in two patients) occurred in unoperated patients (7 (95% CI 2 to 21)/1000 patient years). Although no patient showed fast progression (≥0.3 m/s/year), the peak velocity evolution over time increased faster in females compared with males (first time spline: 0.8 m/s, p=0.017).ConclusionIn adulthood, SVAS patients showed a stable clinical course without rapid progression. While cardiovascular events occurred in this young cohort, they were mostly obsereved in those with additional congenital heart defects, suggesting a more optimistic view for SVAS itself. No significant differences in outcomes were observed in patients with/without Williams-Beuren syndrome. Overall, SVAS tends to follow a more benign course in adulthood compared with childhood, potentially allowing for less intensive follow-up- though follow-up should still be individualised based on associated congenital heart defects and cardiovascular risks.

Introduction: Defective elastic lamellae and smooth muscle cell (SMC) accumulation are characteristics of diverse obstructive arterial diseases (e.g., atherosclerosis, pulmonary hypertension, and supravalvular aortic stenosis [SVAS]) as well as physiological closure of the ductus arteriosus (DA). Mechanistic links between defective elastin and SMC proliferation are not well elucidated. Methods: Immunostaining for proliferation marker Ki67 was performed on wild-type (WT) and Eln(-/-) mouse aortas at embryonic day (E) 13.5 and E15.5 because elastin (ELN) is expressed in the mouse aorta from E14. Bulk RNA-seq was conducted on mouse aortic SMCs isolated from WT or Eln(-/-) embryos at E15.5. As sphingosine kinase 1 (SPHK1) was found as a highly promising candidate, its expression was evaluated in human SVAS patient aortas and in mouse Eln(-/-) aortas and WT DA. S1P receptor 1 (S1PR1) activity was assessed in aortic SMCs from S1pr1(knock-in/knock-in), H2B-GFP mice. Genetic deletion of Sphk1 in SMCs was performed on the elastin mutant background. Pharmacological SPHK1 inhibition was evaluated on both elastin mutants and WT embryos. Regulatory mechanisms of SPHK1 were assessed by mRNA stability assay and TRANSFAC database analysis. Results: SMC hyperproliferation was first observed in Eln(-/-) aorta at E15.5, prior to morphological differences. Bulk RNA-seq revealed that Sphk1 is the most upregulated transcript in Eln(-/-) aortic SMCs at E15.5. Reduced ELN increases SPHK1 levels in SMCs of human patient aortas and mouse aorta and DA. S1PR1 expression and activity are increased by elastin insufficiency. SMC Sphk1 deletion attenuates SMC proliferation and muscularization in the elastin-defective aorta, leading to extended viability of Eln(-/-) mice. Similarly, pharmacological SPHK1 inhibition ameliorates elastin aortopathy but leads to patent DA in WT mice. mRNA stability assay indicated Sphk1 is upregulated by enhanced transcription. TRANSFAC and bulk RNA-seq data suggested that transcription factor early growth response 1 (Egr1) induces Sphk1 transcription. Indeed, EGR1 was upregulated in elastin mutant aortas and DA. Conclusions: Elastin deficiency upregulates SPHK1 transcription, leading to SMC proliferation and hypermuscularization in elastin aortopathy as well as during physiological DA closure. Inhibiting SPHK1 is a promising therapeutic strategy for elastin aortopathy and for select congenital heart diseases in which patent DA maintains circulation.

The appropriate age for surgical repair of asymptomatic congenital supravalvular aortic stenosis (SVAS) is still unknown. The purpose of this research was to assess the safety and effectiveness of various operation ages when managing SVAS. Consecutive asymptomatic SVAS pediatric patients in the Beijing Fuwai and Yunnan Fuwai hospitals over a period of 18 years were retrospectively analyzed. Patients were classified as follows: age <2.0 years (y) (n = 84), 2.0-5.0 y (n = 72), and >5.0 y (n = 92). The primary safety endpoint was in-hospital death or extracorporeal membrane oxygenation (ECMO) needed. The primary effectiveness outcome was re-operation or restenosis during follow-up. To calculate the hazard ratios (HR), Cox regression with inverse probability of treatment weighted was utilized. At the time of surgery, the median age of the 248 patients that were included was 4 y (interquartile range (IQR): 1.8-6.5). For the primary safety outcome, 7 (8.3%) patients in the age <2.0 y group had in-hospital death or ECMO needed, while no patients in the age 2.0-5.0 y and age>5.0 y groups (p = 0.001). The median follow-up was 25.5 months (IQR: 7.0-59.0). Compared with the age 2.0-5.0 y group, the age <2.0 y group and age >5.0 y group had a higher risk of re-operation or restenosis (age <2.0 y, HR = 3.27, 95% CI 1.25-8.60; age >5.0 y, HR = 2.87, 95% CI 1.19-6.91). Asymptomatic children with SVAS without other cardiovascular abnormalities should be considered for delayed surgical intervention until 2 years of age, and then surgery should be conducted as soon as possible. Children with severe symptoms should undergo surgery immediately, regardless of age. ChiCTR2300067851, https://www.chictr.org.cn/showproj.html?proj=177491.