Genetic Testing for Supravalvar Aortic Stenosis: What to Do When It Is Not Williams Syndrome.

BACKGROUND: We aimed to describe the frequency and yield of genetic testing in supravalvar aortic stenosis (SVAS) following negative evaluation for Williams-Beuren syndrome (WS). METHODS AND RESULTS: This retrospective cohort study included patients with SVAS at our institution who had a negative evaluation for WS from May 1991 to September 2021. SVAS was defined as (1) peak supravalvar velocity of ≥2 meters/second, (2) sinotubular junction or ascending aortic Z score <-2.0, or (3) sinotubular junction Z score <-1.5 with family history of SVAS. Patients with complex congenital heart disease, aortic valve disease as the primary condition, or only postoperative SVAS were excluded. Genetic testing and diagnoses were reported. Of 162 patients who were WS negative meeting inclusion criteria, 61 had genetic testing results available (38%). Chromosomal microarray had been performed in 44 of 61 and was nondiagnostic for non-WS causes of SVAS. Sequencing of 1 or more genes was performed in 47 of 61. Of these, 39 of 47 underwent ELN sequencing, 20 of 39 (51%) of whom had a diagnostic variant. Other diagnoses made by gene sequencing were Noonan syndrome (3 PTPN11, 1 RIT1), Alagille syndrome (3 JAG1), neurofibromatosis (1 NF1), and homozygous familial hypercholesterolemia (1 LDLR1). Overall, sequencing was diagnostic in 29 of 47 (62%). CONCLUSIONS: When WS is excluded, gene sequencing for SVAS is high yield, with the highest yield for the ELN gene. Therefore, we recommend gene sequencing using a multigene panel or exome analysis. Hypercholesterolemia can also be considered in individuals bearing the stigmata of this disease.

Long-term Outcomes After Surgical Intervention for Congenital Supravalvar Aortic Stenosis in Children.

BACKGROUND: Primary supravalvar aortic stenosis (SVAS) is a rare congenital cardiovascular condition that can coexist with Williams-Beuren syndrome, coronary artery involvement, aortic coarctation, and pulmonary artery stenosis. SVAS repair can be achieved with low perioperative mortality, but long-term survival remains less well understood. We used the Pediatric Cardiac Care Consortium, a multicenter United States-based registry for pediatric cardiac operations, to assess long-term outcomes after SVAS repair. METHODS: We used Kaplan-Meier plots and Cox proportional hazards regression to examine factors associated with postdischarge deaths. These included sex, age-group, weight z-score, coexisting conditions (Williams-Beuren syndrome, coronary artery involvement, coarctation, and pulmonary artery stenosis), surgical techniques, and era, defined as early (1982-1995) or late (1996-2003). Survival was assessed by matching with the National Death Index through 2021. RESULTS: Of 333 patients who met inclusion criteria, 313 (94.0%) survived to discharge and 188 (60.1%) had identifiers for National Death Index matching. Over a median follow-up of 25.2 years (interquartile range, 21.1-29.4 years), 17 deaths occurred. The 30-year survival after discharge from SVAS repair was 88.7% (95% CI, 82.9%-94.8%). Infantile surgery and non-Williams-Beuren syndrome were associated with decreased 30-year survival. From the various repairs, the 2-sinus technique had better outcomes compared with all other types, except the 3-sinus technique (nonsignificant difference). Adjusted analysis revealed infantile age and type of repair as associated with postdischarge probability of death. CONCLUSIONS: These data demonstrate favorable long-term outcomes after SVAS repair, except for the infantile group that was associated with more diffuse arteriopathy. As techniques continue to evolve, future studies are warranted to investigate their long-term outcomes.

Long-term Surgical Outcomes of Supravalvar Aortic Stenosis: Modified Simple Sliding Aortoplasty.

This study investigated long-term outcomes and factors associated with reoperations in patients who underwent surgical repair of congenital supravalvar aortic stenosis (SVAS). A total of 39 consecutive patients who underwent congenital SVAS repair from 1999 through 2018 were included. Aortic root geometry was evaluated by measuring the ratio of the sinotubular junction diameter to the aortic annulus diameter (STJ/AVA) on echocardiography and proportion of intercommissural distance (ICD) of each sinus on computed tomography. The median age and weight at the time of operation were 4.3 years and 16.9 kg, respectively. Williams syndrome was associated in 25 patients (64.1%). Modified simple sliding aortoplasty (MSSA) was mostly used (n = 35, 89.7%). The median follow-up duration was 9.5 years. There were no early deaths and 1 late death. Overall survival rate was 97.0% at 15 years. There were 7 reoperations during follow-up. Freedom from reoperation for left ventricular outflow tract obstruction and all-cause reoperation were 91.9% and 80.4%, respectively. Age younger than 2 years at initial repair were associated with all-cause reoperation in the univariable analysis. In 35 patients who underwent MSSA, the degree of aortic regurgitation was equal to or less than mild in all patients during follow-up. Their median STJ/AVA on postoperative echocardiography was 0.95 (0.84-1.02). SVAS repair with MSSA provided excellent long-term survival with well-preserved aortic valve competence. Age younger than 2 years at initial repair might be associated with reoperation.

The Sinotubular Junction-to-Aortic Annulus Ratio as a Determinant of Supravalvar Aortic Stenosis Severity.

Supravalvar aortic stenosis (SVAS) severity guides management, including decisions for surgery. Physiologic and technical factors limit the determination of SVAS severity by Doppler echocardiography and cardiac catheterization in Williams syndrome (WS). We hypothesized SVAS severity could be determined by the sinotubular junction-to-aortic annulus ratio (STJ:An). We reviewed all preintervention echocardiograms in patients with WS with SVAS cared for at our center. We measured STJ, An, peak and mean Doppler gradients, and calculated STJ:An. We created 2 mean gradient prediction models. Model 1 used the simplified Bernoulli's equation, and model 2 used computational fluid dynamics (CFD). We compared STJ:An to Doppler-derived and CFD gradients. We reviewed catheterization gradients and the waveforms and analyzed gradient variability. We analyzed 168 echocardiograms in 54 children (58% male, median age at scan 1.2 years, interquartile range [IQR] 0.5 to 3.6, median echocardiograms 2, IQR 1 to 4). Median SVAS peak Doppler gradient was 24 mm Hg (IQR 14 to 46.5). Median SVAS mean Doppler gradient was 11 mm Hg (IQR 6 to 21). Median STJ:An was 0.76 (IQR 0.63 to 0.84). Model 1 underpredicted clinical gradients. Model 2 correlated well with STJ:An through all severity ranges and demonstrated increased pressure recovery distance with decreased STJ:An. The median potential variability in catheterization-derived gradients in a given patient was 14.5 mm Hg (IQR 7.5 to 19.3). SVAS severity in WS can be accurately assessed using STJ:An. CFD predicts clinical data well through all SVAS severity levels. STJ:An is independent of physiologic state and has fewer technical limitations than Doppler echocardiography and catheterization. STJ:An could augment traditional methods in guiding surgical management decisions.

Long-term Surgical Prognosis of Primary Supravalvular Aortic Stenosis Repair.

BACKGROUND: Supravalvular aortic stenosis (SVAS) represents a heterogeneous group, including Williams syndrome, familial elastin arteriopathy, sporadic cases, and others. This study sought to evaluate long-term outcomes of SVAS repair. METHODS: A total of 87 patients underwent surgical repair of congenital SVAS at Boston Children's Hospital in Boston, Massachusetts, between 1997 and 2017. A total of 41 patients had Williams syndrome, and 46 did not. Of the 46 patients who did not have Williams syndrome, 23 had sporadic SVAS, and 13 had familial elastin arteriopathy. Demographic data and outcomes were reviewed and analyzed from medical records. RESULTS: The median age at operation was 2.9 years. Mean z score of the sinotubular junction was -3.29 ± 1.42 and of the aortic root was -0.09 ± 1.19. A total of 26% (n = 22) patients had coronary ostium stenosis, and 41% (n = 9) of them required patch plasty. Survival rates at 5, 10, and 20 years were all 94.3%. Freedom from left ventricular outflow tract reoperation at 5, 10, and 20 years was 78.5%, 70.3%, and 70.3%, respectively. Freedom from aortic arch reintervention at 5, 10, and 20 years was 98.6%, 94.3%, 89.3%, respectively. In risk factors analysis, age younger than 1 year, z scores of the aortic valve and aortic root, and concomitant right ventricular outflow tract surgical repair were predictive of the need for reoperation and reintervention for left or right ventricular outflow tract obstruction. CONCLUSIONS: Excellent long-term survival rates can be achieved with surgical repair of SVAS. Age younger than 1 year, small aortic valve and aortic root z scores, and concomitant right ventricular outflow tract surgical repair were predictors of reoperation and reintervention.

Early and mid-term outcomes after surgical repair of congenital supravalvular aortic stenosis with the Doty technique.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the Doty surgical approach in pediatric patients with congenital supravalvular aortic stenosis (SVAS) by examining early and mid-term outcomes. METHODS: Surgical repair using the Doty technique was performed in a total of 10 pediatric patients with SVAS between January 2005 and July 2015 at this clinic. These patients were evaluated retrospectively. Demographic characteristics, echocardiographic findings, and clinical outcomes were analyzed. RESULTS: The mean patient age was 4.8±3.9 years. Williams-Beuren syndrome was diagnosed in 4 of the patients. Early mortality was observed in 1 patient with diffuse SVAS. At the final follow-up (mean follow-up: 3.7±1.2 years; range: 6-61 months), echocardiograms revealed a mean pressure gradient of 14±4.2 mmHg. Two patients displayed minimal aortic insufficiency during the follow-up period. No reoperation or reintervention was required. CONCLUSION: The Doty technique is an anatomically and technically effective surgical approach to treating SVAS.

Surgical Correction of Supravalvar Aortic Stenosis: 52 Years' Experience.

OBJECTIVES: Supravalvar aortic stenosis (SVAS) is a rare congenital anomaly. The "single-patch technique," "'two sinus augmentation with an inverted Y-patch" (both nonsymmetrical corrections), "three-patch technique," and the "slide aortoplasty" (both symmetrical corrections) are the techniques implemented by the majority of surgeons for the correction of SVAS. In the few studies that compared these techniques, no technique was shown to be superior over another. The aim of the present study is to review the 52-year experience with the surgical correction of SVAS in two of four congenital cardiothoracic surgical centers in the Netherlands. METHODS: We retrospectively reviewed all patient files of those who underwent an operation to correct their SVAS, between 1962 and 2014 in our centers. Patients were divided according to their operating technique. These groups were compared using the end points freedom from reoperation and mortality. RESULTS: A total of 49 patients were included, 23 (46.9%) patients in the nonsymmetrical group and 26 (53.1%) patients in the symmetrical group. Survival after 20 years in the nonsymmetrical group was 80% (standard error [SE]: 0.091) and in the symmetrical group was 85% (SE: 0.085; P = .163). Freedom from reoperation after 20 years in the nonsymmetrical group was 88% (SE: 0.079) and in the symmetrical group was 71% (SE: 0.107; P = 0.313). CONCLUSION: In this patient group, there is no significant difference in survival and freedom from reoperation between the different surgical techniques for SVAS repair. Compared to the survival in the general population, the survival of SVAS patients is remarkably low. Apparently, SVAS is not a benign disease and probably patients should be followed more closely for the rest of their lives.

Diminutive Porcelain Ascending Aorta With Supravalvular Aortic Stenosis.

This report describes the case of a 49-year-old man with a medical history significant for congenital aortic stenosis. The patient presented with progressive shortness of breath and decreased stamina and was found to have a concentric, diminutive porcelain ascending aorta with diffuse supravalvular aortic stenosis. We describe treatment with an aortic root augmentation and Bentall procedure using hypothermic circulatory arrest.

Evaluation of the congenital supravalvular aortic stenosis by different imaging modalities.

A 36-year-old female was admitted to hospital exhibiting chest pain, dyspnea, and a heart murmur on the right upper sternal border, radiating to both carotid arteries. The blood pressure of the patient's right arm exceeded the pressure in the left by 25 mm Hg (Coanda effect). In spite of laboratory results that did not fall outside the expected range, the left ventricle was revealed to be hypertrophic following electrocardiography. Transthoracic echocardiography revealed a severe supravalvular aortic stenosis (SVAS) with a peak Doppler velocity of 6.04 cm/s and an estimated mean pressure gradient of 89 mm Hg, with moderate aortic and mitral regurgitation. Contrast-enhanced computed tomography (CCT) indicated a partial hourglass-shaped narrowing of the ascending aorta. Lesions associated with supravalvular stenosis of the pulmonary artery, patent ductus arteriosus, and aortic coarctation were ruled out by the CCT. Congenital SVAS is a rare heart condition, and three anatomically distinct forms have been described. The most common type is the "hourglass," which produces a marked thickening and disorganization of the aortic tissue, producing a constricting annular ridge at the superior margin of the sinuses of Valsalva.

[Reintervention with percutaneous balloon angioplasty in patients with congenital heart disease with left-sided obstructions]. / Reintervención con angioplastía percutánea con balón en enfermos con cardiopatías congénitas con obstrucciones izquierdas.

BACKGROUND: Left-sided cardiac obstructions represent 15% of congenital heart disease (CHD). The treatment in adults is surgical; however, balloon dilation by interventional catheterization can alleviate the symptoms in pediatric patients to allow them to reach the target height. The aim was to determine the survival and the factors associated with reintervention in patients with CHD with left-sided obstruction treated with balloon angioplasty. METHODS: A cohort study was conducted in patients aged 4 to 17 years with left-sided heart obstruction (valvular stenosis [VS], supravalvular aortic stenosis [SAS], coarctation of the aorta [CA]) successfully treated with balloon angioplasty. The follow-up was of 10 years and the outcome variable was the restenosis with reintervention criteria. Pediatric stage at the time of the procedure, nutritional status, residual gradient, and presence of genetic syndromes were considered prognostic variables. For statistical analysis, measures of central tendency and dispersion were used. Chi squared was employed in qualitative variables and Kruskal-Wallis in quantitative variables. RESULTS: We had a total of 110 patients: 40% had CA, 35% VS, and 25% SAS. 39% required reintervention: 80% in SAS, 35% in CA, and 14% in VS. CONCLUSION: The intervention balloon is a stopgap measure that allows patients with left-sided obstructions to reach the target height.

Introducción: las obstrucciones izquierdas representan 15% de las cardiopatías congénitas (CC). El tratamiento en la edad adulta es quirúrgico; no obstante, la dilatación con balón puede paliar los síntomas en edad pediátrica para permitir que alcancen la talla diana. El objetivo fue determinar la sobrevida y los factores asociados a la reintervención en enfermos con CC con obstrucción izquierda tratados con plastía con balón. Métodos: se realizó un estudio de cohorte en pacientes entre 4 y 17 años con cardiopatías de obstrucción izquierda (estenosis valvular, supravalvular y coartación aórtica) tratados con angioplastía con balón exitosa. El seguimiento fue de 10 años y la variable de desenlace fue la reestenosis con criterios para reintervención. Se consideraron variables pronósticas la etapa pediátrica al momento del procedimiento, el estado nutricional, el gradiente residual y la presencia de síndromes genéticos. Se usaron medidas de tendencia central y dispersión. Se usó chi cuadrada en variables cualitativas y Kruskal-Wallis en variables cuantitativas. Resultados: fueron 110 pacientes; 40% presentó coartación aórtica, 35% estenosis valvular y 25% estenosis supravalvular aórtica. El 39% requirió reintervención y la frecuencia fue la siguiente: 80% en estenosis supravalvular, 35% en coartación aórtica y 14% en estenosis valvular aórtica. Conclusión: la intervención con balón es una medida paliativa que permite a los enfermos con obstrucciones izquierdas alcanzar la talla diana.

High-pressure balloon dilation in a dog with supravalvular aortic stenosis.

A 6-month-old female intact Goldendoodle was presented for diagnostic work up of a grade IV/VI left basilar systolic heart murmur. An echocardiogram was performed and revealed a ridge of tissue distal to the aortic valve leaflets at the sinotubular junction causing an instantaneous pressure gradient of 62 mmHg across the supravalvular aortic stenosis and moderate concentric hypertrophy of the left ventricle. Intervention with a high-pressure balloon dilation catheter was pursued and significantly decreased the pressure gradient to 34 mmHg. No complications were encountered. The patient returned in 5 months for re-evaluation and static long-term reduction in the pressure gradient was noted.

Cerebral Hyperperfusion Syndrome After Surgical Repair of Congenital Supravalvular Aortic Stenosis.

Although cerebral hyperperfusion syndrome is rarely encountered, this condition can be serious after procedures that increase cerebral blood flow; most reports are related to carotid revascularization. Sharp cerebral hemodynamic changes, along with impaired cerebrovascular autoregulation, are the main mechanisms contributing to this syndrome. We report a patient who underwent surgical correction for congenital supravalvular aortic stenosis and presented with postoperative hypertension, headache, impairment of consciousness, and cerebral edema 2 days after operation. He recovered well when the blood pressure declined and the brain edema subsided. Cerebral hyperperfusion syndrome was considered, and this uncommon neurologic complication of cardiac operations is discussed.

Left coronary artery stenosis causing left ventricular dysfunction in two children with supravalvular aortic stenosis.

Congenital supravalvar aortic stenosis (SVAS) is an arteriopathy associated with Williams-Beuren syndrome (WBS) and other isolated elastin gene deletions. Cardiovascular manifestations associated with WBS are characterized by obstructive arterial lesions such as SVAS and pulmonary artery stenosis in addition to bicuspid aortic valve and mitral valve prolapse. However, coronary artery ostial stenosis may be associated with SVAS, and it increases the risk of sudden death and may complicate surgical management. In this report, we present our experience with two patients having SVAS and left coronary artery ostial stenosis with associated left ventricular dysfunction.

Outcome of surgical correction of congenital supravalvular aortic stenosis with two- and three-sinus reconstruction techniques.

BACKGROUND: Several surgical techniques for the treatment of congenital supravalvular aortic stenosis have been developed, yet there is no consensus about the optimal approach. We reviewed our institutional experience with 2- and 3-sinus reconstruction techniques. METHODS: Thirty-eight patients operated on for supravalvular aortic stenosis between 1987 and 2012 in our institution were analyzed retrospectively. Eight patients (21%) were infants and in 5 (13.2%) diffuse stenosis was present. Mean peak pressure gradient was 86.1±28.7 mm Hg preoperatively. Surgical procedures included single-patch enlargement (McGoon, n=3), inverted bifurcated-patch aortoplasty (Doty, n=22), 3-sinus patch augmentation (Brom, n=8), and autologous slide aortoplasty (n=5). Major concomitant procedures were performed in 10 patients (26.3%). RESULTS: Early mortality was 2.6%. Follow-up continued for a median of 7.5 years (range 3 weeks to 22 years). Overall survival estimates were 94% and 90% and overall freedom from reoperation was 83% at 5 and 20 years, respectively. No differences were found between surgical techniques in respect to survival, clinical course, hemodynamic outcome, or freedom from reoperation rates. A significantly worse outcome in regard to survival and reoperation rates was observed in infants. CONCLUSIONS: Our study demonstrates equally good results for the repair of supravalvular aortic stenosis with both 2- and 3-sinus reconstruction. No evidence of a superior outcome for 3-sinus reconstruction techniques was found. Operation in infancy is an important factor associated with unfavorable outcome.

An unexpected cause of cardiac arrest during laparoscopy in an infant with supravalvar aortic stenosis.

Patients with congenital supravalvar aortic stenosis (SVAS) with associated biventricular outflow tract obstruction and coronary artery abnormalities have a tenuous myocardial oxygen supply/demand relationship. They are at increased risk of acute myocardial ischemia and sudden death, especially during anesthesia. Furthermore, resuscitation during cardiac arrest is frequently unsuccessful. We report a case of perioperative cardiac arrest due to an unexpected cause in a 2 month old with SVAS during a laparoscopic Nissen fundoplication.

Late outcomes for surgical repair of supravalvar aortic stenosis.

BACKGROUND: We reviewed our experience with the surgical management of supravalvar aortic stenosis (SVAS) to determine long-term outcomes and factors related to late reoperation. METHODS: Between August 1956 and May 2009, 78 patients (50 males) underwent surgical correction of SVAS. Median age was 10.4 years (range, 16 days to 55.2 years). Mean preoperative gradient was 57.2±21.9 mm Hg with a mean peak gradient of 99.5±34.8 mm Hg. Supravalvar aortic stenosis was discrete in 51 patients (64%) and diffuse in 27 patients (35%). Aortic valve stenosis was present in 22 patients (29%). Williams-Beuren syndrome was present in 32 patients (41%). RESULTS: Surgery was either a diamond-shaped patch in 67 patients (85.9%) or a pantaloons-shaped patch in 11 patients (14.1%). Aortic valve intervention was required in 20 patients (25.64%). Mean gradient immediately after repair was 25±25 mm Hg, with 13 patients (16.7%) having a residual gradient. A high residual gradient was more likely in the diffuse group (odds ratio, 3.73; 95% confidence interval, 1.07 to 12.98). There were 2 (2.6%) early deaths, both with diffuse SVAS. Median follow-up was 19.8 years; maximum was 48.5 years. The mean gradient across the left ventricular outflow tract at late follow-up was 8.8 mm Hg (95% confidence interval, 3.7 to 14.01). Overall survival was estimated at 90%±7%, 84%±9%, and 8%2±10% at 5, 10, and 20 years, respectively. Predictors of mortality were age younger than 2 years (p=0.021), diffuse SVAS (p=0.045), aortic valve stenosis (p=0.032), and high postoperative gradient (p=0.023). Presence of Williams-Beuren syndrome did not affect survival (p=0.305). Freedom from late reoperation was 97%±4%, 93%±7%, and 86%±10% at 5, 10, and 20 years, respectively. Significant aortic valve disease (p<0.001) and diffuse SVAS (p=0.009) were risk factors for late reoperation. CONCLUSIONS: Surgical repair for SVAS can be performed with a single-patch technique with good long-term outcome. Late mortality and need for reoperation are more likely with diffuse SVAS or the presence of aortic valve stenosis.

Patch annulo-aortoplasty in an adult patient with congenital supravalvular aortic stenosis and a small aortic annulus.

A 39-year-old woman with familial homozygous hypercholesterolemia had supravalvular and valvular aortic stenosis. Modified Nick's procedure and aortic valve replacement was performed to relieve both the supravalvular and annular stenoses. At surgery, the ascending aorta was found to be narrowing at the level of the sinotubular junction, which was compatible with congenital supravalvular aortic stenosis. Histological examination of the aortic cusps showed sclerotic change due to hypercholesterolemia. These findings indicated that familial homozygous hypercholesterolemia caused valvular aortic stenosis and exacerbated congenital supravalvular aortic stenosis.