Cardiovascular findings in Williams-Beuren Syndrome: Experience of a single center with 127 cases.

Williams-Beuren syndrome (WBS) is a rare, microdeletion syndrome characterized by facial dysmorphisms, intellectual disability, a friendly personality, cardiovascular and other abnormalities. Cardiovascular defects (CVD) are among the most prevalent characteristics in WBS, being supravalvular aortic stenosis (SVAS) the most frequent, followed by peripheral pulmonary stenosis (PPS). A comprehensive retrospective review of medical records of 127 patients with molecular diagnosis of WBS, in a period of 20 years, was done to evaluate the incidence, the natural history of cardiovascular disease, and the need for surgical intervention, including heart transplantation (HT). A total of 94/127 patients presented with CVD. Of these 94 patients, 50% presented with SVAS and 22.3% needed heart surgery and/or cardiac catheterization including one that required HT due to severe SVAS-related heart failure at 19 years of age. The patient died in the postoperative period due to infectious complications. Cardiovascular problems are the major cause of sudden death in patients with WBS, who have a significantly higher mortality risk associated with surgical interventions. There is a higher risk for anesthesia-related adverse events and for major adverse cardiac events following surgery. End-stage heart failure due to myocardial ischemia has been described in WBS patients and it is important to consider that HT can become their only viable option. To our knowledge, the case mentioned here is the first HT reported in an adolescent with WBS. HT can be a viable therapeutic option in WBS patients with adequate evaluation, planning, and a multidisciplinary team to provide the required perioperative care and follow-up.

Supravalvular Aortic Stenosis and the Risk of Premature Death Among Patients With Homozygous Familial Hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p <0.001). This result was further confirmed in the multivariable Cox regression models. After adjusting for age, sex, low density lipoprotein cholesterol (LDL_C)-year-score, lipid-lowering drugs, cardiovascular disease, and carotid artery plaque, SVAS was an independent risk factor of premature death in HoFH on the multivariate analysis (hazard ratio 4.45; 95% confidence interval, 1.10 to 18.12; p = 0.037). In conclusion, a significantly increased risk of premature death was observed in HoFH patients with SVAS. Our study emphasized the importance of careful and aggressive management in these patients when appropriate.

[Supravalvular aortic stenosis with and without coronary lesions in pediatrics. A Lebanese study]. / STÉNOSE SUPRAVALVULAIRE AORTIQUE AVEC OU SANS LÉSIONS CORONAIRES EN PÉDIATRIE--ÉTUDE LIBANAISE.

OBJECTIVE: This study aims to analyze several parameters concerning the supravalvular aortic stenosis (SVAS) in children such as age of diagnosis, place of residence, the existence of a metabolic disorder or dysmorphic syndrome and possible damage to the coronary ostia, the means of diagnosis and outcome of these patients. MATERIALS AND METHODS: A large group of patients (2868) with congenital heart disease enrolled between 1 May 1999 and 30 April 2010 at the National Register of Pediatric and Congenital Heart Disease, Lebanese Society of Cardiology. RESULTS: SVAS were found in 14 patients (0.5%) aged 8.5 months to 15 years. The Williams Beuren syndrome was the most common etiology (6 cases) without ostial stenosis, asymptomatic and not treated, followed by forms without dysmorphic syndrome (5 cases) and without ostial stenosis, one patient was operated because of severe SVAS; finally, 3 cases of homozygous familial hypercholesterolemia treated differently: a patient had a successful liver transplantation at age of 4.5 years but has developed, despite the normalization of cholesterol level, a SVAS associated with severe ostial lesions 10 years after transplantation, another treated by coronary artery bypass graft surgery and the latter treated medically. CONCLUSION: SVAS is a very rare disease, but its discovery must lead to search for coronary lesions especially in presence of homozygous familial hypercholesterolemia. The ultrasound monitoring is mandatory and is designed to detect this anomaly and early coronary lesions. The slightest suspicion should carry out more extensive explorations to detect ostial stenosis.

Cardiovascular abnormalities, interventions, and long-term outcomes in infantile Williams syndrome.

OBJECTIVE: To determine the prevalence of cardiovascular abnormalities (CVA) and outcomes in patients with Williams syndrome presenting before 1 year of age. STUDY DESIGN: A retrospective review was undertaken of consecutive patients with WS at our institution from January 1, 1980, through December 31, 2007. WS was diagnosed by an experienced medical geneticist and/or by fluorescence in situ hybridization. CVA were diagnosed with the use of echocardiography, cardiac catheterization, or computerized tomographic angiography. Freedom from intervention was determined using Kaplan-Meier analysis. RESULTS: The study group was 129 patients with CVA. Age at presentation was 127 +/- 116 days, with follow-up of 8.0 +/- 7.5 years (0 to 42 years). The most common lesions were peripheral pulmonary artery stenosis (62%) and supravalvar aortic stenosis (57%). Other CVA were common. CV interventions were performed in 29%, with 58% of those before 1 year. Freedom from intervention was 85%, 73%, and 66% at 1, 5, and 25 years, respectively. Four patients died. CONCLUSIONS: CVA are the most common manifestations of infantile Williams syndrome and occur with greater frequency than previously reported. In those with CVA, interventions are common and usually occur by 5 years of age. Most of these patients do not require intervention on long-term follow-up, and overall mortality is low.

Recurrent coarctation: is surgical repair of recurrent coarctation of the aorta safe and effective?

BACKGROUND: Persistence or recurrence of stenosis is a complication of coarctation repair and is associated with major long-term morbidity. The rate of recurrence varies significantly, depending on the age of the patient, technique at initial repair, and the arch anatomy. We reviewed our experience with surgical repair of recurrent coarctation of the aorta and compared it with our institutional experience with balloon aortoplasty. METHODS: We retrospectively reviewed our experience with 1,012 patients undergoing initial repair of coarctation between 1960 and 2008. During that time, 103 patients (10%) required reintervention. Median age at reintervention was 6.5 years (range, 2 weeks to 44 years) and median weight was 12 kg (range, 1.9 to 94 kg). Fifty-nine patients with recoarctation had surgical repair, and 44 patients were treated with balloon aortoplasty with or without stent placement. RESULTS: Ninety-five percent of patients have been followed up (median time, 14.2 years; range, 2 months to 42 years). There were 5 late deaths. Actuarial survival was 98% at 15 and 40 years in patients with surgical reintervention, and it was 91% (p = 0.001) at 15 years in patients with balloon aortoplasty reintervention. A second redo coarctation of the aorta reintervention was performed in 12 patients: 8 patients after percutaneous intervention (nonsurgical) and 4 patients after surgical recoarctation repair. The median interval between first and second reintervention was 3.5 years (range, 1 month to 14 years). One patient who had two dilations underwent a third and fourth reintervention: patch enlargement and pseudoaneurysm resection. Freedom from reintervention in the surgical group was 96% at 15 years and 94% at 40 years, which was compared with actuarial freedom from reintervention for patients with percutaneous intervention (balloon/stent) at 15 years (82%; p < 0.001). CONCLUSIONS: Our study demonstrates that surgical repair of recurrent coarctation of the aorta can be performed safely and with excellent results. The recurrence after surgical reintervention is low, and most patients to date have not required further intervention. Balloon aortoplasty as an alternative method of managing recoarctation is efficient and less invasive than surgery; however, well-described complications may occur. Recurrence rates with angioplasty are significantly higher than with surgery.

Polyvascular extracoronary atherosclerotic disease in patients with coronary artery disease.

BACKGROUND: Cardiovascular diseases are the number one killer in the developed countries, accounting for approximately half of all deaths, with the leading causes being myocardial infarction and ischaemic stroke. In line with the ageing population, the prevalence of coronary artery disease (CAD), lower extremity peripheral arterial disease (PAD), supra-aortic arterial disease (SAD) and renal stenosis (RAS) is increasing. Polyvascular atherosclerosis (PVA) coexisting in several territories has an adverse effect on cardiovascular morbidity and mortality. AIM: To determine prevalence, coexistence and predictors of significant PAD, SAD and RAS in patients with suspected CAD. METHODS: Based on angiography, the frequency of coexisting CAD, SAD, PAD and RAS (stenosis > or =50%) was determined in 687 (487 male) consecutive patients, aged 63.5 +/- 9.1 years, referred for coronary angiography. RESULTS: Significant CAD was found in 545 (79.3%) patients (1-vessel in 164; 2-vessel in 157; 3-vessel in 224). SAD, RAS and PAD were found in 136 (19.8%), 55 (8%), and 103 (15%) patients, respectively. Of the 545 patients with confirmed CAD, 346 (63.5%) had stenoses limited to coronary arteries. 2-, 3- and 4-level PVA was found in 130 (23.8%), 61 (11.2%) and 8 (1.5%) patients, respectively. Of the 142 patients without CAD, 127 (89.4%) had no significant stenoses elsewhere, 12 (8.5%) had 1 extracoronary territory and 3 (2.1%) had 2-territory involvement. Backward stepwise binary logistic regression analysis showed the following independent predictors of at least 2-level PVA: 2- and 3-vessel CAD (p < 0.001), hyperlipidaemia (p = 0.067), smoking (p < 0.001), creatinine level > or = 1.3 ml/dl (p < 0.001), lower extremities claudication (p < 0.001) and female gender (p = 0.003). The relative risk of having at least 2-territory PVA was 15.7-fold higher in patients with claudication, 2.1-fold in patients with multivessel CAD, 2.8-fold for serum creatinine level > 1.3 mg/dl; and 1.9-fold, 2.4-fold and 2-fold in patients with hyperlipidaemia, smokers and women, respectively. CONCLUSIONS: Significant atherosclerosis in extracoronary arterial territories is present in 36% of patients with documented CAD. With advancing PVA, accumulation of atherosclerosis risk factors, previous atherothrombotic events and more severe CAD is observed.

Supra-aortic extracranial artery atherosclerotic lesions in patients diagnosed for coronary artery disease: prevalence and predictors.

BACKGROUND: In patients with coronary artery disease (CAD), the presence of atherosclerotic lesions in other vascular beds is associated with a markedly worse prognosis. AIM: To determine the prevalence and predictors of extracranial supra-aortic artery atherosclerotic disease (SAD) in patients with suspected CAD. METHODS: Supra-aortic artery angiography was performed in 379 consecutive patients aged 64.2 +/- 8.8 years (231 male) referred for coronary angiography. Clinical and laboratory data (total cholesterol, LDL, HDL cholesterol, hs-CRP, creatinine level) and left ventricular ejection fraction were analysed. RESULTS: Significant stenosis (> or =50% by quantitative angiography) within at least one main branch of the coronary arteries was found in 314 (82.8%) patients, including 87 (27.7%), 96 (30.6%) and 131 (41.7%) with 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Among all 379 patients, stenosis > or =50% of the carotid artery was documented in 9.5%, vertebral in 13.7%, and subclavian in 7.4% of patients. We found 130 stenoses > or =50% within the supra-aortic arteries in 90 patients (23.7% of the whole study group, and 28.7% of CAD patients), including 42 internal carotid artery stenoses in 36 patients, 58 vertebral artery stenoses in 52, and 30 subclavian stenoses in 28 patients. In 24 (6.3%) patients more than one SAD was present. The SAD > or =50% was found in 8 (12.3%) patients without significant CAD, in 22 (25.3%), 17 (17.7%) and 43 (32.8%) with 1-, 2- and 3-vessel CAD, respectively (p = 0.001). Independent predictors of SAD > or =50% identified by multivariate analysis were: previous neurological ischaemic event (p = 0.001), CAD (p = 0.015), creatinine level (p = 0.031), male gender (p = 0.001), claudication (p < 0.001) and low HDL cholesterol (p = 0.033). The following independent predictors of vertebral and/or subclavian artery stenosis > 50% were identified: CAD severity (p = 0.002), creatinine level (p = 0.024), male gender (p = 0.013), claudication (p < 0.001) and low HDL cholesterol level (p = 0.059). CONCLUSIONS: In a large patient sample, we have found that significant supra-aortic atherosclerosis is present in a quater of patients with suspected CAD. Importantly, SAD prevalence increases with CAD severity. Previous neurological ischaemic event, CAD, creatinine level, male gender, claudication and hyperlipidaemia were identified as independent predictors of SAD > or =50%.

Cardiovascular spectrum in Williams-Beuren syndrome: the Mexican experience in 40 patients.

In this study, we have identified and evaluated the cardiovascular anomalies associated with Williams-Beuren syndrome in children.In a retrospective, lineal, and observational study, we reviewed the files of children who were seen from 1980 through 2005 (25 years) after a clinical diagnosis of Williams-Beuren syndrome.Forty children were diagnosed with this syndrome at the National Institute of Pediatrics in Mexico City. Of these, 32 (80%) were found to have congenital heart defects. The male-to-female ratio was 1.3:1 and ages ranged from 6 months to 15 years (mean, 4.4 years) at the time of diagnosis. All of the patients had morphologic and genetic characteristics typical of the syndrome.We emphasize the cardiovascular aspects from a clinical point of view. Supravalvular aortic stenosis was our most frequent finding, in 18 of 32 patients (56%); gradient differences in these patients ranged from 14 to 81 mmHg. Five patients showed combined lesions, the most frequent being supravalvular aortic stenosis in combination with pulmonary artery brachial stenosis, or with atrial and ventricular defects. Patients with incomplete atrioventricular defect and bicuspid aortic valve, as were seen at our hospital, have not to our knowledge been reported in other studies.One of the patients was scheduled for balloon dilation; another was scheduled for surgery; a 3rd patient was operated on twice for the placement of an aorto-aortic bridge; another underwent ventricular septal defect closure; and yet another underwent aortoplasty, this last dying shortly after surgery.

Diffuse supravalvular aortic stenosis with multiple stenoses of the branches of arcus aorta in a child.

We give details of a sporadic case with congenital supravalvular aortic stenosis associated with critical stenosis of the left carotid artery, and severe stenosis of the innominate artery at their origins as well as excessive dilatations of both the right and the left coronary arteries.

Williams-Beuren syndrome in the Hong Kong Chinese population: retrospective study.

OBJECTIVE: To estimate the incidence and document the clinical characteristics of Williams-Beuren syndrome in the Hong Kong Chinese population. DESIGN: Cytogenetic analysis and retrospective study. SETTING: Clinical Genetic Service, Department of Health, Hong Kong. PATIENTS: Forty-one Chinese patients with Williams-Beuren syndrome. MAIN OUTCOME MEASURES: From 1 January 1995 to 30 June 2002, fluorescence in situ hybridisation was used to confirm diagnoses in 41 cases of Williams-Beuren syndrome by detecting chromosome 7q microdeletion. Case records were reviewed, the incidence of the condition in the local population was estimated, and the main clinical characteristics were determined. RESULTS: The minimal incidence of Williams-Beuren syndrome in this locality was estimated to be approximately 1 per 23500 live births. Common dysmorphic facial features included periorbital fullness (83%), full lips (80%), a long philtrum (51%), a flat nasal bridge (41%), and abnormal teeth (37%). No patients had a stellate iris. The majority (82%) had at least one documented cardiac anomaly; among these patients, peripheral pulmonary stenosis was diagnosed in 61% and supravalvular aortic stenosis in 45%. Nearly all (93%) of the study group exhibited developmental delay. CONCLUSION: As in the West, patients with Williams-Beuren syndrome in the Hong Kong Chinese population display craniofacial dysmorphism, cardiovascular anomalies, and mental deficiency. Supravalvular aortic stenosis-the cardiac defect most commonly associated with Williams-Beuren syndrome in western countries-is less common than peripheral pulmonary stenosis in this region. Studies involving periodic cardiovascular evaluation are needed to confirm if this difference is significant.

Peculiaridades da estenose aórtica congênita / Peculiarities of congenital aortic stenosis

A estenose aórtica é uma cardiopatia congênita comum na cardiologia pediátrica. Ela pode ocorrer em vários níveis ù valvar, subvalvar e/ou supravalvar aórtica. A estenose supravalvar aórtica pode vir acompanhada de estenoses pulmonares, devendo-se lembrar aqui a associação com hipercalcemia e síndrome de Williams. No diagnóstico diferencial da estenose subaórtica, é importante a lembrança da cardiomiopatia hipertrófica obstrutiva. Embora as crianças com estenose valvar aórtica possam ser assintomáticas, muitos recém-nascidos têm a forma grave, necessitando de tratamento precoce com valvoplastia com balão percutânea e/ou cirurgia, além de suporte inotrópico e ventilatório. No adulto, a lesão mais comum é a valva aórtica bicúspide, que pode levar à estenose no decorrer do tempo e a outras anormalidades em aorta ascendente e à necessidade de intervenção cirúrgica.