UNASSIGNED: To determine the effectiveness and safety of different patch materials in the treatment of pediatric patients with congenital supravalvular aortic stenosis (SVAS).
UNASSIGNED: 218 consecutive SVAS patients (age < 14 years) who underwent surgery from Beijing Fuwai and Yunnan Fuwai hospital between 2002 and 2020 were included. Patients were divided into the pericardium patch group (133 (61.0%)), modified patch group (43 (19.7%)) and artificial patch group (42 (19.3%)). The primary safety endpoint was patch-related adverse complications (post-operation patch hemorrhage or aortic sinus aneurysm at 2-year follow-up). The primary effectiveness outcome was the re-operation or restenosis at 2-year follow-up. Multivariable cox regression was used to obtain the hazard ratio (HR).
UNASSIGNED: The median age at operation was 43.5 months (IQR 24.0-73.0). Only three patients had patch-related adverse complications, and no difference existed among the three groups (p = 0.763). After a median follow-up of 24.0 months (IQR 6.0-48.0), patients with a pericardium patch had a lower re-operation or restenosis rate compared with the other two groups (pericardium patch vs modified patch, HR = 0.30, 95% CI 0.12-0.77; pericardium patch vs artificial patch, HR = 0.33, 95% CI 0.13-0.82), even in the main subgroup and sensitivity analysis.
UNASSIGNED: In pediatric patients, the safety of autologous pericardium patch is acceptable, along with lower rates of middle-term re-operation or restenosis.
UNASSIGNED: http://www.chictr.org.cn, number: ChiCTR2300067851.

Supravalvular aortic stenosis (SVAS) is a congenital malformation associated with Williams-Beuren syndrome. It is characterized by severe stenosis of the sinotubular junction. The smooth muscle layer is thickened due to an alteration of the Elastin gene. The treatment is surgical and there are several techniques to relieve obstruction which range from the single-patch technique to the replacement of all three aortic sinuses with three patches. However, the optimal technique is still unclear. The objective of this article is to carry out a bibliographic review of surgical techniques for SVAS and the description of the application of the Doty technique for a 4-year-old infant at the Roberto Gilbert Elizalde Hospital.
La estenosis aórtica supravalvular es una malformación congénita asociada al síndrome de Williams-Beuren. Se caracteriza por una severa estenosis en la unión sinotubular. La capa de músculo liso se engrosa debido a una alteración en el gen Elastina. El tratamiento es quirúrgico y existen varias técnicas para aliviar la obstrucción, que van desde la técnica de un solo parche hasta el reemplazo de los tres senos aórticos con tres parches. Sin embargo, la técnica óptima aún no está clara. El objetivo de este artículo es realizar una revisión bibliográfica de las técnicas quirúrgicas para estenosis valvular aórtica supravalvular y describir la aplicación de la técnica de Doty en una niña de 4 años en el Hospital Roberto Gilbert Elizalde.

We report a 17-year-old male with supravalvular stenosis, initial failure to thrive and delayed early development, short stature, acromelia, dysmorphic facial features, hypertelorism, macrocephaly, syringomyelia, hypertension, and anxiety disorder. Fluorescent in situ hybridization (FISH), chromosomal microarray analysis (CMA), and exome sequencing (ES) were nondiagnostic. Combined optical genome mapping (OGM) and genome sequencing (GS) showed a complex rearrangement including an X chromosome with a 22.5 kb deletion in band Xq28 replaced by a 61.4 kb insertion of duplicated chromosome 7p22.3 material. The deletion removes the distal 3\' untranslated region (UTR) of FUNDC2, the entire CMC4 and MTCP1, and the first five exons of BRCC3. Transcriptome analysis revealed absent expression of CMC4 and MTCP1 and BRCC3 with normal transcript level of FUNDC2. The inserted duplication includes only one known gene: UNCX. Similar overlapping Xq28 deletions have been reported to be associated with Moyamoya disease (MMD), short stature, hypergonadotropic hypogonadism (HH), and facial dysmorphism. Although he has short stature, our patient does not have signs of Moyamoya arteriopathy or hypogonadism. The structurally abnormal X chromosome was present in his mother, but not in his unaffected brother, maternal uncle, or maternal grandparents. We propose that the combination of his absent Xq28 and duplicated 7p22.3 genomic material is responsible for his phenotype. This case highlights the potential of combined OGM and GS for detecting complex structural variants compared with standard of care genetic testing such as CMA and ES.

Various surgical techniques have been introduced to treat supravalvular aortic stenosis (SVAS). However, there is no consensus on the optimal approach. This study aimed to analyze the outcomes of surgical treatment of SVAS and determine the optimal strategy. The Kaplan-Meier curve was used to demonstrate the survival estimates. The Cox proportional hazard model was used to identify risk factors for residual aortic stenosis and residual stenosis-related reintervention. From December 2008 to December 2023, 98 patients with SVAS undergoing surgical repair in our institution were included [McGoon group, n = 62; Doty group, n = 36]. There were 2 in-hospital deaths and 1 late death. The survival rates at 1, 5, and 15 years were 98.0%, 96.7%, and 96.7%, respectively in the whole cohort. Residual aortic stenosis occurred in 18 patients. Multivariable analysis showed that preoperative gradient ≥ 90 mmHg (P = 0.002) and Williams syndrome (P = 0.002) were incremental risk factors for residual aortic stenosis, but surgical technique (P = 0.579) was not a risk factor for residual aortic stenosis. In the McGoon group, patients with diffuse type had worse freedom from residual aortic stenosis than patients with discrete type (P = 0.007). However, in the Doty group, patients with diffuse type had comparable freedom from residual aortic stenosis to patients with discrete type (P = 0.911). Residual stenosis-related reintervention occurred in 15 patients. Fifteen patients all underwent residual aortic stenosis-related reintervention. Of 15 patients, 6 patients also underwent residual pulmonary stenosis-related reintervention. On multivariate analysis, Williams syndrome (P < 0.001), preoperative sinotubular junction (STJ) z-score < - 3.5 (P = 0.051), and Doty repair (P = 0.033) were found to be independent risk factors associated with residual stenosis-related reintervention. In the whole cohort, freedom from residual stenosis-related reintervention at 1, 5, and 15 years were 97.8%, 89.3% and 76.1%, respectively. Surgical repair of SVAS can be safely achieved using different techniques, with similar long-term mortality. Compared with McGoon repair, Doty repair was significantly associated with decreased residual aortic stenosis rates in patients with diffuse-type SVAS. Patients with preoperative gradient ≥ 90 mmHg or Williams syndrome are more prone to residual aortic stenosis. Surgical technique was not associated with residual aortic stenosis rates. Williams syndrome, preoperative STJ z-score < - 3.5, and Doty repair are associated with higher residual stenosis-related reintervention rates.

Cardiovascular system involvement is quite common and the leading cause of morbidity and mortality in patients with Williams syndrome (WS), most of whom need surgery. The present study aimed to provide a detailed evaluation of the features of surgical procedures and outcomes of patients with WS given as single-center experience, and additionally to make a detailed review from Türkiye.
Thirty-five children with WS diagnosed between the years 1992 and 2021 were evaluated retrospectively including cardiovascular data, surgical treatment features, and outcomes. A total of six articles from Türkiye were evaluated.
A total of 35 patients with Williams Syndrome (24 male) with a median age of cardiologic diagnosis of 6 months (range, 2 days-6 years) were evaluated. The cardiac defects of the patients with WS were found as supravalvular aortic stenosis (SVAS) (n=30, 85%) and peripheral pulmonary stenosis (PPS) (n=21, 65%). Additional cardiac anomalies were seen in 71% patients. The rate of SVAS and PPS surgery in all patients with WS was 77.1%. The median surgical age of the patients was 2.5 years (range, 7 months-15.5 years). No patients died due to surgery. But one patient died because of ventricular tachycardia due to anesthesia at the beginning of angiography. A total of 138 (63% male) patients with WS were evaluated from the articles published in Türkiye. Of 138 patients, 64.4% had SVAS, 52.1% had PPS, and 39.8% had additional cardiac anomaly. The median follow-up period ranged from 17 months to 18 years, and six (4.3%) patients died in the early postoperative period.
Cardiovascular system involvement is extremely common and is the leading cause of morbidity and mortality in patients with WS, often requiring surgical intervention. As seen in our study including 35 patients with WS and in publications from Türkiye, SVAS in patients with WS generally requires surgery, especially in the first year of life. PPS, on the other hand, requires surgery less frequently than SVAS, and pulmonary stenosis appears to decrease over time.

Congenital arterial stenosis such as supravalvar aortic stenosis (SVAS) are highly prevalent in Williams syndrome (WS) and other arteriopathies pose a substantial health risk. Conventional tools for severity assessment, including clinical findings and pressure gradient estimations, often fall short due to their susceptibility to transient physiological changes and disease stage influences. Moreover, in the pediatric population, the severity of these and other congenital heart defects (CHDs) often restricts the applicability of invasive techniques for obtaining crucial physiological data. Conversely, evaluating CHDs and their progression requires a comprehensive understanding of intracardiac blood flow. Current imaging modalities, such as blood speckle imaging (BSI) and four-dimensional magnetic resonance imaging (4D MRI) face limitations in resolving flow data, especially in cases of elevated flow velocities. To address these challenges, we devised a computational framework employing zero-dimensional (0D) lumped parameter models coupled with patient-specific reconstructed geometries pre- and post-surgical intervention to execute computational fluid dynamic (CFD) simulations. This framework facilitates the analysis and visualization of intricate blood flow patterns, offering insights into geometry and flow dynamics alterations impacting cardiac function. In this study, we aim to assess the efficacy of surgical intervention in correcting an extreme aortic defect in a patient with WS, leading to reductions in wall shear stress (WSS), maximum velocity magnitude, pressure drop, and ultimately a decrease in cardiac workload.

OBJECTIVE: The aim of this study was to identify the prevalence and anatomic characteristics of coronary artery lesions and their associated postoperative risk in patients undergoing supravalvular aortic stenosis repair.
METHODS: The association between structural risk factors, postoperative ST-segment changes, and major adverse cardiac events was explored using logistic regression and the Fisher\'s exact test.
RESULTS: In 51 consecutive patients with supravalvular aortic stenosis treated between 2000 and 2017, a total of 48 coronary lesions were identified in 27 patients (53%). Prominent ostial ridge (type I) was the most common coronary lesion, followed by small ostium with (IIIb) or without (IIIa) diffuse long-segment coronary narrowing, and adhesion of the coronary cusp (type II). There were 54 concomitant coronary procedures, including 43 primary corrections and 11 revisions. Thirty-three patients underwent supravalvular aortic stenosis repair with a bifurcated patch, of which 13 (39.4%) had right coronary artery distortion/kinking requiring patch plication (n = 8) and reimplantation (n = 5). Postoperative major adverse cardiac events (MACE) occurred in 9 patients (17.6%), including 3 deaths, 4 needing mechanical circulatory support, and 6 experiencing ventricular arrhythmias. Twenty-two patients (43.1%) had postoperative ST-segment changes, including 13 early changes that resolved within 24 h and 9 persistent changes lasting >24 h. Patients with type III lesions were associated with postoperative persistent ST-segment change (P = 0.04) and these lesions independently predicted postoperative MACE (P = 0.02). Patients with pre-existing coronary lesions were at elevated risk of right coronary artery distortion/kinking (P = 0.045).
CONCLUSIONS: The prevalence of ST-segment changes and MACE is high in patients undergoing supravalvular aortic stenosis repair. The preoperative presence of complex coronary lesions is the most important predictor for postoperative major adverse cardiac events.

Supravalvular aortic stenosis (SVAS) has been well described in Williams-Beuren Syndrome and non-syndromic elastin (ELN) mutations. Non-syndromic ELN mutations are inherited in an autosomal dominant pattern with incomplete penetrance and variable expressivity. ELN haploinsufficiency leads to progressive arteriopathy, typically affecting the aortic sinotubular junction. Multi-level pulmonary stenosis has also been reported and biventricular obstruction may portend a worse prognosis. Fetal presentation of ELN mutation with SVAS has not been previously reported in the literature. We present a case of fetal diagnosis of SVAS and multi-level pulmonary stenosis in a family with a known pathogenic ELN mutation (Exon 6, c.278del [p.Pro93Leufs*29]). On the fetus\' initial fetal echo, there was only mild flow acceleration through the aortic outflow tract, however, she went on to develop progressive bilateral obstruction. In the early post-natal period, the child was clinically asymptomatic and showed similar mild SVAS and mild valvar and supravalvular pulmonary stenosis. Our case highlights the need for serial monitoring of fetuses with suspected or confirmed ELN arteriopathy.

The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate-intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed), and exercised AS (AS-Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal-Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS-Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS-Sed. Myocardial proteome analysis showed that AS-Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta-oxidation than C-Sed. AS-Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS-Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate-intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats.

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