Cardiovascular disease in Williams syndrome.

PURPOSE OF REVIEW: Williams syndrome is a multisystem disorder seen with some regularity at most pediatric centers and usually fairly often at larger centers. Cardiovascular abnormalities, because of elastin deficiency, are the leading cause of morbidity and mortality in patients with Williams syndrome. The present article presents a review of the most recent developments regarding the cardiovascular issues in Williams syndrome. RECENT FINDINGS: Cardiovascular abnormalities occur in 80% of patients with Williams syndrome, the majority of which are arterial stenoses. The stenoses seen in Williams syndrome now appear to arise from deficient circumferential arterial growth. Pharmacological therapies aimed at improving the vascular stenoses have shown some promise in animal models. Surgical outcomes for supravalvar aortic stenosis are good at most centers. Transcatheter interventions are largely ineffective in Williams syndrome. Multilevel surgical pulmonary artery reconstruction has excellent results for peripheral pulmonary artery stenosis. Periprocedural risk stratification and management algorithms may decrease the risk of cardiovascular complications. SUMMARY: Cardiovascular abnormalities are a major determining factor in the clinical picture and trajectory of patients with Williams syndrome. Advances in surgical techniques, medical therapeutic options, and periprocedural management hold promise for significant improvements in the cardiovascular outcomes of these patients.

Single-stage surgical repair of a complex pathology in Williams syndrome.

Williams syndrome is caused by a gene deletion of chromosome 7. A majority of the cases are sporadic with typical facial appearance, cardiac anomalies, and mental retardation. We report a rare case of Williams syndrome associated with supravalvular aortic stenosis, subvalvular aortic membrane, mitral regurgitation, aortic coarctation, and patent ductus arteriosus. The patient had undergone a single-stage surgical repair with satisfactory results at 5 months of follow-up.

Loeffler's endocarditis presenting with acute abdominal aortic obstruction.

Loeffler's endocarditis is a complication of diseases associated with the idiopathic hypereosinophilic syndrome, which is characterised by persistently elevated blood eosinophil counts with symptoms and signs of organ involvement especially in the heart, vascular system, nervous system and bone marrow. We report the involvements of the endocardium and aorta, without endomyocardial fibrosis and the complete resolution of the endocardial eosinophilic infiltration with steroids and anticoagulation therapy.

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.

Better late than never: diagnosis and successful treatment in late adulthood of supravalvular aortic stenosis secondary to Williams-Beuren syndrome.

This is a case report of a patient diagnosed at age 50 with supravalvular aortic stenosis secondary to Williams-Beuren Syndrome and successfully treated with aortic valve replacement and excision of supravalvular tissue.

Discrete contributions of elastic fiber components to arterial development and mechanical compliance.

OBJECTIVE: Even though elastin and fibrillin-1 are the major structural components of elastic fibers, mutations in elastin and fibrillin-1 lead to narrowing of large arteries in supravalvular aortic stenosis and dilation of the ascending aorta in Marfan syndrome, respectively. A genetic approach was therefore used here to distinguish the differential contributions of elastin and fibrillin-1 to arterial development and compliance. METHODS AND RESULTS: Key parameters of cardiovascular function were compared among adult mice haploinsufficient for elastin (Eln(+/-)), fibrillin-1 (Fbn1(+/-)), or both proteins (dHet). Physiological and morphological comparisons correlate elastin haploinsufficiency with increased blood pressure and vessel length and tortuosity in dHet mice, and fibrillin-1 haploinsufficiency with increased aortic diameter in the same mutant animals. Mechanical tests confirm that elastin and fibrillin-1 impart elastic recoil and tensile strength to the aortic wall, respectively. Additional ex vivo analyses demonstrate additive and overlapping contributions of elastin and fibrillin-1 to the material properties of vascular tissues. Lastly, light and electron microscopy evidence implicates fibrillin-1 in the hypertension-promoted remodeling of the elastin-deficient aorta. CONCLUSIONS: These results demonstrate that elastin and fibrillin-1 have both differential and complementary roles in arterial wall formation and function, and advance our knowledge of the structural determinants of vascular physiology and disease.

Cardiovascular abnormalities in patient with Williams-Beuren syndrome.

We present a case of a 42-year-old male patient with severe supravalvular aortic stenosis associated with aortic and mitral valve stenosis as well as an anomalous origin of the right coronary ostium caused by deletion in the q11.23 region of the human chromosome 7 in a patient with Williams-Beuren syndrome.

Ascending Aortic Stenting for Acute Supraaortic Stenosis From Graft Collapse.

A 78-year-old man with remote type-A dissection presented with acute-onset dyspnea. Twenty-two years prior, treatment for his aortic disease required replacement of ascending and arch aneurysms with a polyester graft (Dacron) using the graft inclusion technique. He presented currently in cardiogenic shock. Echocardiography demonstrated new severe hypokinesis of all apical segments. Left-heart catheterization revealed a 120 mm Hg intragraft gradient. Computed tomography arteriography was unrevealing, but intraaortic ultrasound demonstrated critical intragraft stenosis. A balloon expandable stent (Palmaz stent, Cordis, Milpitas, CA) was deployed in the stenotic region with gradient resolution. The patient later underwent aortic root replacement and ascending aneurysm repair (Bio-Bentall technique) and is doing well at 24 months.

Familial hypercholesterolemia supravalvular aortic stenosis and extensive atherosclerosis.

Familial hypercholesterolemia is an autosomally dominant disorder caused by various mutations in low-density lipoprotein receptor genes. This can lead to premature coronary atherosclerosis and cardiac-related death. The symptoms are more severe in the homozygous type of the disease. Premature malignant atherogenesis leading to aortic root abnormalities causing supravalvular aortic stenosis is rare. Our case demonstrates the diagnostic imaging findings of the phenotype of patients who have severe elevated LDL with familial hypercolesterolemia.

Two Cases of Surgical Management of Supravalvular Aortic Stenosis in Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia is a rare autosomal dominant disorder caused by gene mutations of the low-density lipoprotein receptor, generally characterized by three major signs-hyper low-density lipoprotein cholesterolemia, tendon/skin xanthomas, and premature atherosclerosis disease-beginning in childhood and including supravalvular aortic stenosis. To the best of our knowledge, only a few successful surgical cases for supravalvular aortic stenosis in these patients have been reported. We report two cases of homozygous familial hypercholesterolemia with severe supravalvular aortic stenosis and coronary artery disease associated with very small aortic root, managed by aortic root replacement concomitant with coronary artery bypass graft surgery, which resulted in excellent postoperative outcomes.

Pathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolism.

Pathological cardiac hypertrophy leads to derangements in lipid metabolism that may contribute to the development of cardiac dysfunction. Since previous studies, using high saturated fat diets, have yielded inconclusive results, we investigated whether provision of a high-unsaturated fatty acid (HUFA) diet was sufficient to restore impaired lipid metabolism and normalize diastolic dysfunction in the pathologically hypertrophied heart. Male, Wistar rats were subjected to supra-valvar aortic stenosis (SVAS) or sham surgery. After 6 weeks, diastolic dysfunction and pathological hypertrophy was confirmed and both sham and SVAS rats were treated with either normolipidic or HUFA diet. At 18 weeks post-surgery, the HUFA diet failed to normalize decreased E/A ratios or attenuate measures of cardiac hypertrophy in SVAS animals. Enzymatic activity assays and gene expression analysis showed that both normolipidic and HUFA-fed hypertrophied hearts had similar increases in glycolytic enzyme activity and down-regulation of fatty acid oxidation genes. Mass spectrometry analysis revealed depletion of unsaturated fatty acids, primarily linoleate and oleate, within the endogenous lipid pools of normolipidic SVAS hearts. The HUFA diet did not restore linoleate or oleate in the cardiac lipid pools, but did maintain body weight and adipose mass in SVAS animals. Overall, these results suggest that, in addition to decreased fatty acid oxidation, aberrant unsaturated fatty acid metabolism may be a maladaptive signature of the pathologically hypertrophied heart. The HUFA diet is insufficient to reverse metabolic remodeling, diastolic dysfunction, or pathologically hypertrophy, possibly do to preferentially partitioning of unsaturated fatty acids to adipose tissue.

Cardiac arrest related to anaesthesia in Williams-Beuren syndrome. / Parada cardíaca relacionada con la anestesia en el síndrome Williams-Beuren.

Williams-Beuren syndrome is the clinical manifestation of a congenital genetic disorder in the elastin gene, among others. There is a history of cardiac arrest refractory to resuscitation manoeuvres in anaesthesia. The incidence of myocardial ischaemia is high during anaesthetic induction, but there are patients who do not have this condition yet also have had very serious cardiac events, and issues that are still to be resolved. Case descriptions will enable the common pathophysiological factors to be defined, and decrease morbidity and mortality. We report the case of a 3-year-old boy with cardiac arrest at induction, rescued with circulatory assistance with extracorporeal membrane oxygenation and hypothermia induced for cerebral protection.

Supravalvular aortic stenosis after arterial switch operation.

Supravalvular aortic stenosis as a late complication of transposition of the great arteries is very rare, and only a few cases have been reported. We describe the case of a 14-year-old girl who developed supravalvular aortic stenosis as a late complication of the arterial switch operation for transposition of the great arteries. The narrowed ascending aorta was replaced with a graft. The right pulmonary artery was transected to approach the ascending aorta which adhered severely to the main pulmonary trunk, and we obtained a good operative field.

Valvular and supravalvular aortic stenosis in heterozygous familial hypercholesterolemia, a case report.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by a high level of LDL-cholesterol and frequent coronary atherosclerosis. We studied a 64 year old woman with heterozygous (hetero) FH, who showed symptoms of chest pain and dyspnea with no other coronary risk factors than post-menopause and hypercholesterolemia. Although her coronary symptoms didn't reveal significant stenosis on coronary angiography, she had severe aortic valvular and supravalvular stenosis at the ascending aorta, which qualified her for aortic valve replacement. Moreover, a coronary flow study revealed functional ischemia with a reduction of the coronary flow reserve. We report a case of valvular and supravalvular aortic stenosis corrected by aortic valve replacement, a rare complication of hetero FH.

De novo obstruction after supravalvular aortic stenosis repair in Williams-Beuren syndrome.

Williams-Beuren syndrome is characterized by diffuse arteriopathy due to elastin gene deficiency. We present a patient with de novo supravalvular stenosis due to excessive intimal hyperplasia after a previous repair. This case report supports in vitro and animal studies that have linked elastin deficiency to increased cellular proliferation in the vessel wall with the subsequent development of obstructive lesions.