Incidence Of Bicuspid Aortic Valve Research Articles

Experimental evidence of the genetic hypothesis on the etiology of bicuspid aortic valve aortopathy in the hamster model

Bicuspid aortopathy occurs in approximately 50% of patients with bicuspid aortic valve (BAV), the most prevalent congenital cardiac malformation. Although different molecular players and etiological factors (genetic and hemodynamic) have been suggested to be involved in aortopathy predisposition and progression, clear etiophysiopathological mechanisms of disease are still missing. The isogenic (genetically uniform) hamster (T) strain shows 40% incidence of BAV, but aortic dilatations have not been detected in this model. We have performed comparative anatomical, histological and molecular analyses of the ascending aorta of animals with tricuspid aortic valve (TAV) and BAV from the T strain (TTAV and TBAV, respectively) and with TAV from a control strain (HTAV). Aortic diameter, smooth muscle apoptosis, elastic waviness, and Tgf-β and Fbn-2 expression were significantly increased in T strain animals, regardless of the valve morphology. Strain and aortic valve morphology did not affect Mmp-9 expression, whereas Mmp-2 transcripts were reduced in BAV animals. eNOS protein amount decreased in both TBAV and TTAV compared to HTAV animals. Thus, histomorphological and molecular alterations of the ascending aorta appear in a genetically uniform spontaneous hamster model irrespective of the aortic valve morphology. This is a direct experimental evidence supporting the genetic association between BAV and aortic dilatation. This model may represent a population of patients with predisposition to BAV aortopathy, in which increased expression of Tgf-β and Fbn-2 alters elastic lamellae structure and induces cell apoptosis mediated by eNOS. Patients either with TAV or BAV with the same genetic defect may show the same risk to develop bicuspid aortopathy.

Incidence of bicuspid valve related aortic dissection: a systematic review and meta-analysis.

BackgroundThe true incidence of bicuspid valve-related aortic dissection (AD) is extremely difficult to ascertain. This review aimed to provide the reported cumulative incidence of bicuspid aortic valve (BAV)-related AD in actively monitored study populations.MethodsFour electronic databases were used to perform literature searches. A meta-analysis of proportions or means were performed for categorical and continuous variables, as appropriate. Survival data was calculated from the aggregation of Kaplan-Meier (KM) curves from the included studies, where reported.ResultsA total of 4,330 patients were identified in eleven studies. A cumulative incidence of bicuspid valve-related AD of 0.6% across a median follow-up time of 9 years was identified. Actuarial survival across this monitored population at 1, 3, 5 and 10 years was 97.2%, 96.7%, 92.45%, and 81.1%, respectively.ConclusionsThis systematic review and meta-analysis identified a low incidence of AD across the examined follow-up period. Large, prospective studies involving early identification of bicuspid valve pathology, recruitment, and follow-up of BAV cohorts with comparison to the baseline population are required to most accurately determine the outcomes of these patients.

Clinical characteristics of severe aortic stenosis patients combined with diabetes mellitus after transcatheter aortic valve replacement and short-term outcome.

Type 2 diabetes (T2DM) is a common comorbidity in patients with degenerative aortic stenosis (AS).As a key item of the American Society of Thoracic Surgeons (STS) score, it has a vital impact on the clinical prognosis of traditional thoracic surgery. T2DM has an adverse effect on the morbidity and mortality of cardiovascular diseases. At the same time, studies have shown that T2DM are associated with myocardial hypertrophy and remodeling, decreased left ventricular function, and worsening heart failure symptoms in the AS patients. Transcatheter aortic valve replacement (TAVR) as an interventional method to replace the aortic valve has better safety for middle and high risk patients in surgery, but the impact of T2DM on the clinical outcome of TAVR in AS patients is not clear.By analyzing the clinical and image characteristics of patients with AS and T2DM who received TAVR treatment, so as to explore the effect of T2DM on the perioperative complications and prognosis of TAVR. A total of 100 consecutive patients with severe AS, who underwent TAVR treatment and were followed up for more than 1 month, were selectedin the Second Xiangya Hospital of Central South University from January 2016 to December 2020.Among them, 5 patients who were treated with TAVR due to simple severe aortic regurgitation were not included, therefore a total of 95 patients with severe aortic stenosis were enrolled in this study.The age of the patients was (72.7±4.8) years old, and there were 58 males (61.1%), and the patients with moderate or above aortic regurgitation had 30 cases (31.6%). The patients were divided into a diabetic group and a non-diabetic group according to whether they were combined with T2DM.There was no statistical difference in age, gender, body mass index (BMI), STS score, and New York Heart Association (NYHA) cardiac function classification between the 2 groups (all P>0.05). The primary end point was defined as a composite event consisting of all-cause death and stroke one month after surgery, and the secondary end point was defined as TAVR-related complications immediately after surgery and one month after surgery.The preoperative clinical data, cardiac ultrasound data, CT data, postoperative medication and the incidence of each endpoint event were compared between the 2 groups.The predictive model of adverse events was constructed by single factor and multivariate logistic regression. Compared with the non-diabetic group, the diabetic group had high blood pressure and chronic renal insufficiency.There was no significant difference in preoperative ultrasound echocardiography between the 2 groups. Preoperative CT evaluation found that the anatomical structure of the aortic root in the diabetic group was smaller than that in the non-diabetic group, and there was no significant difference in the incidence of bicuspid aortic valve between the 2 groups (all P<0.05). In terms of postoperative medication, the use of statins in the diabetes group was significantly higher than that in the non-diabetic group. In the diabetes group, 6 patients (37.5%) received insulin therapy, and 9 patients (56.3%) received oral medication alone.Univariate logistic regression analysis showed that the all-cause death and stroke compound events was increased in the diabetes group in 30 days after TAVR (OR=6.86; 95% CI: 2.14 to 21.79; P<0.01). Heart disease (OR=2.80; 95% CI: 0.99 to 7.88; P<0.05) and chronic renal insufficiency (OR=3.75; 95% CI: 1.24 to 11.34; P<0.05) were also risk factors for all-cause death and stroke compound events.In a multivariate analysis, after adjusting for age, gender, BMI, comorbidities, N-terminal pro-B type natriuretic peptide (NT-proBNP), total calcification score, ejection fraction, and degree of aortic regurgitation, T2DM was still a risk factor for all-cause death and stroke compound events in 30 days after TAVR (OR=12.68; 95% CI: 1.76 to 91.41; P<0.05). T2DM is a risk factor for short-term poor prognosis in patients with symptomatic severe AS after TAVR treatment. T2DM should play an important role in the future construction of the TAVR surgical risk assessment system, but the conclusions still need to be further verified by long-term follow-up of large-scale clinical studies.

Predictors and Effects of Persistent Hypertension after Successful Treatment of Coarctation of the Aorta

Background: Coarctation of the aorta is a congenital heart disease that sometimes remains clinically silent until adulthood, usually presenting with arterial hypertension. It is well known that after coarctation treatment, many patients remain hypertensive despite successful repair. In this study we approached the predictors and effects of residual hypertension after successful coarctation therapy. Methods: It was a cross sectional observational study involving 50 patients who underwent Coarctation repair/angioplasty in Ain Shams university hospitals. We divided the patients into two groups (hypertensive and normotensive) and we studied their demographic data (e.g., age, gender, age at first repair, follow up period, etc.) to conclude the possible predictors of persistent hypertension in such cases. We also performed full echocardiographic assessment including 3D speckle tracking echocardiography to detect subtle changes in left ventricular systolic functions. Results: Hypertensive patients had significantly higher BMI (29.1 kg/m2) as compared to normotensives (24 kg/m2), p < 0.0001. Age at first CoA intervention was significantly higher in hypertensive patients. Hypertensive patients had significantly lower 3D left ventricular strain measures (Global area strain, global circumferential strain and global longitudinal strain). The incidence of bicuspid aortic valve was significantly higher in the hypertensive group, yet it was not an independent predictor of persistent hypertension. Conclusions: The predictors for residual hypertension post successful CoA repair were late intervention and higher BMI. Bicuspid aortic valve was more common in the hypertensive group. Regarding the effects of such disease domain, treated CoA patients with persistent hypertension tended to have higher LV mass index and lower values of LV deformation.

Association between Cardiac Malformations and Karyotype in Turner Syndrome - a Single Centre Study

Abstract Turner syndrome is characterized by growth failure, pubertal delay and different skeletal, cardiovascular and renal malformations. In this study we investigated the prevalence of cardiac abnormalities and the correlation with the karyotype in girls with Turner syndrome. Methods We conducted a retrospective cohort study of 85 girls with TS aged 0–17 years, divided in two groups: monosomy X and other X chromosome abnormalities (mosaicism and structural X chromosome abnormalities). Echocardiography was performed in all patients. Karyotype was determined from peripheral blood lymphocytes using the G-banding technique. Results Monosomy X was the most frequent karyotype (68.3%). 31% of patients presented different cardiac abnormalities. Bicuspid aortic valve and coarctation of the aorta were the most prevalent heart malformations (16.5% and 11.8% respectively). The girls with monosomy X had a higher prevalence of heart malformations than the girls with other chromosome abnormalities. Bicuspid aortic valve was more frequent in the monosomy X group. Conclusion Monosomy X is associated with a higher incidence of cardiac abnormalities. There were no differences in cardiovascular abnormalities between various karyotypes except the higher incidence of bicuspid aortic valve observed in patients with monosomy X comparing to those with mosaic karyotype and structural X chromosome aberrations.

Proteomic analysis of the ascending aorta in a hamster model of BAV disease

Bicuspid aortic valve (BAV) is the most prevalent human congenital cardiac malformation, which predisposes to ascending aortic dilatation (AD). Disease predisposition probably results from a congenital defect leading to anomalies in both, the morphology of the valve and the histology of the ascending aorta. Altered hemodynamics caused by the abnormal valve morphology would accelerate aortic media degeneration. AD in BAV patients results from medial smooth muscle cell (SMC) apoptosis probably caused by defective cell-matrix adhesion. Alterations of the TGFβ pathway seem to be central in disease initiation and progression, affecting extracellular matrix homeostasis. However, currently there are neither clear pathophysiological mechanisms nor effective biomarkers of disease predisposition or progression.The only spontaneous animal model of BAV disease consists of an inbred (T) strain of Syrian hamsters with a high (40%) incidence of BAV. Although AD has never been described in this model, animals of the T strain show significant SMC apoptosis and altered elastic lamina in the aortic media, irrespective of aortic valve morphology. We reasoned that analysing differentially expressed proteins in the aortic wall of animals with normal aortic valve (TAV) of the T strain compared to a control strain would inform about 1) the validity of the T strain as a model for BAV aortopathy predisposition; 2) the congenital origin of AD associated to BAV; 3) the proteins involved in AD etiology, independent of the effect of hemodynamics.To this aim, we compared the proteome of the ascending aorta of animals with TAV of the T strain (n=6) and a control outbred strain (n=6) by three independent experiments of quantitative proteomics (ESI-Quadrupole-Orbitrap LFQ). The analysis yielded expression data for over 1,954 proteins. Of these, 57 proteins (2.9%) showed concordant expression in at least two of the three experiments and were deregulated over 2.6-fold.Fourteen of these 57 proteins (24.6%) were previously proposed as AD biomarkers in patients. After database search, the 57 selected proteins were found to significantly interact (p<0.05 following FDR adjustment) within 16 molecular pathways and 27 biological processes on the STRING website. Most of these pathways and processes were relevant to AD pathophysiology, of note are the TGFβ non-canonical pathways (10/57; 17.5%; p=0.043), programmed cell death (14/57; 24.6%; p=3.5e-4), cell adhesion (15/57; 26.3%; p=2.4e-4), supramolecular fiber organization (9/57; 15.8%; p=3.8e-4) and stress fiber assembly (2/57; 3.5%; p=0.037).These results were obtained comparing the proteomes of aortas of individuals with TAV from an affected and a control strain. Thus, genetic rather than hemodynamic factors explain the structural abnormalities of the ascending aorta in this model. We propose that the T strain is an appropriate model for AD predisposition, as it replicates the ethiophysiological processes observed in patients. Deep study of our ascending aorta proteome analysis may uncover new molecular players and markers associated with aortopathy predisposition and progression.

Impact of prospective measurement of outflow tracts in prediction of coarctation of the aorta

Prenatal diagnosis of coarctation of the aorta (CoA) is associated with reduced mortality and morbidity, however, accurate prenatal prediction remains challenging. To date, studies have used retrospective measurements of the outflow tracts to evaluate their potential to predict CoA. Our primary objective was to evaluate prospectively acquired measurements of the outflow tracts in fetuses with prenatally suspected CoA. A secondary aim was to report the postnatal prevalence of bicuspid aortic valve in this cohort. Pregnancies with suspicion of isolated CoA and with a minimum of 6 months' postnatal follow-up available were identified from the cardiac database of a tertiary fetal cardiology center in the UK, between January 2002 and December 2017. Measurement of the aortic valve, pulmonary valve, distal transverse aortic arch (DTAA) and arterial duct (AD) diameters were undertaken routinely in fetuses with suspected CoA during the study period. Z-scores were computed using published reference ranges based on > 7000 fetuses from our own unit. Of 149 pregnancies with prenatally suspected CoA included in the study, CoA was confirmed within 6 months after birth in 77/149 (51.7%) cases. DTAA diameter Z-score and the Z-score of second-trimester DTAA/AD diameter ratio were smaller in fetuses with postnatally confirmed CoA than those in false-positive cases (-2.8 vs -1.9; P = 0.039 and -3.13 vs -2.61; P = 0.005, respectively). Multiple regression analysis demonstrated that the Z-scores of DTAA and AD diameters were the only significant predictors of postnatal CoA (P = 0.001). Bicuspid aortic valve was identified in 30% of the false-positive cases. Measurement of DTAA and AD diameter Z-scores can be used to ascertain risk for postnatal CoA in a selected cohort. The high incidence of bicuspid aortic valve in false-positive cases merits further study with respect to both etiology and longer-term significance. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

РЕГІОНАЛЬНІ МІГРАЦІЙНІ ПРОЦЕСИ ТА ЗАХВОРЮВАНІСТЬ НА ДВОСТУЛКОВИЙ АОРТАЛЬНИЙ КЛАПАН У ДІТЕЙ ЗАПОРІЗЬКОЇ ОБЛАСТІ.

Резюме: Формування вроджених вад серця (ВВС) відбувається під впливом генетичних, середовищних та демографічних чинників. Під впливом міграційних процесів, завдяки змінам у внутрішньо популяційній гетерозиготності збільшується мутаційне навантаження, що, у свою чергу, призводить до змін у формуванні захворюваності на вроджені вади серця (ВВС), у тому числі двостулковий аортальний клапан (ДАК).Метою дослідження стало встановлення взаємозв’язків між основними показниками міграції населення та захворюваністю на двостулковий аортальний клапан (ДАК) у мешканців міст та сільських районів Запорізької області, а також внесків у неї міграційних процесів.Матеріали та методи: на підставі даних про захворюваність на найбільш пощирені ВВС серел дитячого населення Запорізької області включаючи двостулковий аортальний клапан (ДАК) та даних обласного управління статистики щодо показників міграції населення регіону, з використанням методів кореляційного та регресійного аналізу, був проаналізований вплив цих показників на захворюваність ДАК.Результати та обговорення: встановлене переважання внутрішньорегіональної та зовнішньої міграції у мешканців міст регіону при достовірному збільшенні в них захворюваності на ДАК. Найбільші внески у захворюваність, у тому числі порівняно з іншими ВВС має число прибулих та вибулих осіб при зовнішньорегіональній міграції. Встановлений вплив окремих міграційних процесів у захворюваність на ДАК може слугувати непрямим показником мутаційного навантаження у окремих субпопуляціях України.

Prevalence and Complications of Bicuspid Aortic Valve in Chinese According to Echocardiographic Database.

As transcatheter aortic valve replacement has become an alternative treatment for patients at high risk for surgical aortic valve replacement, bicuspid aortic valve (BAV) draws our attention again. The reported frequency of BAV was 0.5% to 2% in western population. However, there was no such epidemiologic study in Chinese population. Our study sought to investigate the prevalence and complications of BAV in China by echocardiographic database. A total of 668 cases who were confirmed with BAV, identified from 195,708 echocardiographic records of 157,039 patients in the echocardiographic database of West China Hospital (between June 2008 and June 2012), were analyzed retrospectively. The incidence of BAV was 0.43% in the cohort, and 579 (86.68%) patients were complicated by various degree of aortic valve stenosis or aortic valve regurgitation. The incidence of infective endocarditis and aortic dissection was 0.68% episodes per patient-years with mean age of 42.96 ± 11.25years and 0.18% episodes per patient-years with mean age of 43.00 ± 5.14years, respectively. In conclusion, our study demonstrated that the prevalence of BAV and complications in Chinese was similar to that in the western population.

Abstract 18574: Examination of a Highly Penetrant Mouse Model of Bicuspid Aortic Valve Demonstrates that Endothelial Notch1 is Required for Proper Morphogenesis of the Aortic Valve

Bicuspid aortic valve (BAV) is the most common type of cardiac malformation with an estimated prevalence of 1-2% in the population. BAV results in significant morbidity as it is one of the leading causes of valve stenosis and regurgitation in adults. We previously reported that mutations in the signaling and transcriptional regulator, NOTCH1 , were a cause of BAV in non-syndromic autosomal-dominant human pedigrees. The Notch signaling pathway is critical for multiple cell differentiation processes, and Notch1 is expressed in the developing and adult aortic valve. Recently, we have generated a new highly penetrant mouse model of aortic valve malformations using Notch1 haploinsufficient mice that are backcrossed in a Nos3-null background. Notch1 and Nos3 compound mutant adult mice ( Notch1 +/- ;Nos3 -/- ) display a nearly 100% incidence of BAV. The aortic valves of adult mutant mice are thickened and have associated stenosis and regurgitation. We have also found that by postnatal day 10, compound mutant mice suffer ~50% lethality compared to NOS3 -/- littermates. Here, we have examined Notch1 +/- ;Nos3 -/- embryos at serial timepoints to elucidate the mechanisms underlying BAV. Examination at embryonic day 18.5 (E18.5) demonstrated normal Mendelian ratios and histologic examination revealed thickened, malformed valve leaflets accompanied by other outflow tract abnormalities in NOS3 -/- ;Notch1 -/+ mice, likely contributing to the neonatal lethality. Further investigation at E13.5 and E15.5 indicated that the NOS3 -/- ;Notch1 -/+ aortic valve leaflets were significantly thicker than controls, suggesting that outflow tract cushion formation and early remodeling may be affected. In addition, we have generated mice are null for Nos3 and haploinsufficient for Notch1 in endothelial-derived cells using mice harboring a Notch1 -floxed allele and Tie2-Cre mice. Our preliminary results indicate that NOS3 -/- ; Notch1 fl/+ ;Tie2Cre + mice recapitulate the NOS3 -/- ;Notch1 -/+ cardiac phenotype and suggest that endothelial Notch1 is required for proper development of the aortic valve. Overall our data indicate that loss of endothelial Notch1 results in abnormal remodeling of the outflow tract cushions and contributes to BAV.

Is there an association between bicuspid aortic valve and neuroblastoma?

An association has been reported between neuroblastoma and congenital heart disease, frequently bicuspid aortic valve [Holzer and Franklin. Arch Dis Child 2002;87:61-64; George et al. J Pediatr 2004;144:444-448; Friedman et al. Pediatr Cardiol 1998;19:480-481; Monte et al. Am J Pediatr Hematol Oncol 1985;7:109-116]. To evaluate this in a large patient group with neuroblastoma, we examined echocardiograms of patients with neuroblastoma from 1987 to January 2007 to determine if there was a higher incidence of bicuspid aortic valves compared to the general population without neuroblastoma. We found that only 0.7% of neuroblastoma patients had the congenital heart defect of bicuspid aortic valves compared with 1-2% in the general population [Braverman et al. Curr Prob Cardiol 2005;30:470-522]. Our data show that neuroblastoma is not associated with bicuspid aortic valves.

The presence of bicuspid aortic valve does not predict ventricular septal defect type

Previous studies have identified an increased incidence of bicuspid aortic valve (BAV) in patients with ventricular septal defect (VSD). Because endocardial cushion remodeling contributes to both the formation of semilunar valves and ventricular septation, we hypothesized that examination of humans with BAV and VSD would identify a specific VSD type. We evaluated VSD type in pediatric patients diagnosed with BAV and VSD (n=82) and compared findings to patients diagnosed with VSD and normal aortic valve morphology (n=429). VSD type was described as conoventricular, muscular, inlet or conoseptal using a clinical taxonomy. Based on the contribution of the outflow tract endocardial cushions to the membranous ventricular septum, we expected patients with BAV to have conoventricular VSD. In both patient groups, conoventricular VSD was most common; however, the prevalence was not significantly different when BAV patients were compared to those with normal aortic valve morphology (67% vs. 57%, P=0.11). The primary finding of this study is that despite a developmental link between semilunar valve formation and ventricular septation during cardiogenesis, there is no clear association between BAV and VSD type. This may be due to phenotypic and genetic heterogeneity of BAV and VSD, other modifying factors as manifested by differences in associated CVM, as well as limitations of the clinical taxonomy of VSD.

Transverse arch hypoplasia may predispose patients to aneurysm formation after patch repair of aortic coarctation

Background Thoracic aortic aneurysm after patch repair of aortic coarctation is a potentially lethal complication. We hypothesized that transverse arch hypoplasia in association with patch repair of aortic coarctation predisposes aneurysm formation. Methods A retrospective analysis was performed on all patients undergoing isolated aortic coarctation repair at the University of Virginia Health Systems between 1970 and 1995. Of 244 repairs, 38 patients underwent patch repair. These 38 patients were divided into two groups. The aneurysm group (n = 15) had aortic aneurysms develop at the repair site, which required aneurysmectomy. The nonaneurysm group (n = 23) did not have any aneurysms develop. Univariate analysis and Fisher's exact text were used to identify factors that independently predict aneurysm formation. Results Univariate analysis demonstrated aortic arch hypoplasia associated with patch repair independently predicts future aneurysm formation ( p < 0.01). Patients who had an aneurysm develop also had a similar incidence of bicuspid aortic valves, mild restenosis, and late hypertension compared with patients in the nonaneurysm group. Conclusions Aneurysm formation after patch repair of aortic coarctation develops into a subgroup of patients. Aortic arch hypoplasia associated with coarctation independently predicts future aneurysm formation.

Fusion of valve cushions as a key factor in the formation of congenital bicuspid aortic valves in Syrian hamsters.

Bicuspid aortic valve is the most frequent congenital cardiac malformation in humans. However, the morphogenesis of the defect is still unknown. Previous work showed that, in the Syrian hamster, congenital bicuspid aortic valves with the aortic sinuses arranged in ventrodorsal orientation are expressions of a trait the variation of which takes the form of a continuous phenotypic spectrum, ranging from a tricuspid aortic valve with no fusion of the ventral commissure to a bicuspid aortic valve devoid of any raphe. The present study was designed to elucidate the mechanism involved in the formation of bicuspid aortic valves in Syrian hamsters as a possible starting point for further investigation of this process in humans. The sample examined consisted of 80 embryos, aged between 10 days, 16 hours and 13 days, 1 hour postcoitum. Most (n = 59) of the embryos belonged to a laboratory-inbred family of Syrian hamsters with a high incidence of bicuspid aortic valves. The study was carried out using scanning electron microscopy and histological techniques for light microscopy. Twenty-three embryos showed a still undivided conotruncus. In all of these cases there were six mesenchymal semilunar valve primordia protruding into the lumen of the conotruncus. In a further 29 embryos, the conotruncus had just divided into the aortic and pulmonary channels; the embryos were at the beginning of the valvulogenesis. In 13 of these 29 embryos there were three well-defined aortic valve cushions, right, left, and dorsal, whereas in the other 16, the right and left valve cushions were more or less fused toward the lumen of the aorta; when they were completely fused, only two aortic valve cushions, a ventral and a dorsal, could be identified. In the remaining 28 embryos, the aortic valve cushions showed a marked degree of excavation. In 23 of these cases, the valve exhibited a basically tricuspid architecture, whereas it was unequivocally bicuspid in the other five. All variants of the aortic valve morphologic spectrum occurring in the Syrian hamster develop from three mesenchymal valve cushions, right, left, and dorsal, after normal septation of the conotruncus. The bicuspid condition of the aortic valve is not the consequence of improper development of the conotruncal ridges, conotruncal malseptation, valve cushion agenesis, or lesions acquired after a normal valvulogenesis. Fusion of the right and left valve cushions at the beginning of the valvulogenesis appears to be a key factor in the formation of bicuspid aortic valves. Each aortic valve acquires its specific morphology prior to the end of the valvulogenetic process.

Cartilage in the Aortic Valve and Its Relationship with the Aortic Valve Morphology in Syrian Hamsters

We conducted a light-microscopic histologic study of the aortic valves of 224 Syrian hamsters aged between 1 and 771 days. Most of the hamsters examined belonged to a single laboratory-inbred family with a high incidence of bicuspid aortic valves (BAVs). In 146 specimens the aortic valve was tricuspid, and in 107 of them the ventral commissure was more or less fused. The remaining 78 specimens showed a BAV with the aortic sinuses oriented ventrodorsally. In 33 BAVs a raphe was located in the ventral aortic sinus. Cartilaginous foci were present in the aortic valves of 86 specimens, 40-771 days old. The foci were located at two different sites, namely in the ventral wall of the valve and/or in the dorsal aortic sinus. Statistical analyses substantiate that (1) chondrogenesis begins earlier in BAVs, and especially in those having a raphe, than in tricuspid aortic valves and (2) the location of the cartilaginous foci is significantly associated with the morphology of the aortic valve. The present findings support the hypothesis that, in the Syrian hamster, cartilage forms in the aortic valve as a response to locally intense mechanical stimulation.

Cardiac anomalies in Williams-Beuren syndrome.

We have described some of the cardiological findings in 66 patients with Williams-Beuren syndrome and analysed the two dimensional cross sectional echocardiograms in 61 of them in comparison with normal controls. Supravalvar aortic narrowing was shown in all patients examined echocardiographically and may be a useful diagnostic sign. We documented a 7.8% incidence of systemic hypertension, a 15% clinical and echocardiographic incidence of mitral valve prolapse, and a 11.6% incidence of bicuspid aortic valve.

Echocardiography reveals a high incidence of bicuspid aortic valve in Turner syndrome

The most common cardiac defect in Turner syndrome has been described previously as coarctation of the aorta. We have evaluated 35 consecutive patients with Turner syndrome by clinical examination and by M-mode and two-dimensional echocardiography. Twelve patients (34%) had isolated, nonstenotic bicuspid aortic valve. A high correlation (82%) existed between the presence of a systolic ejection click and echocardiographic evidence of a bicuspid aortic valve. These data indicate that bicuspid aortic valve may be the most common cardiac anomaly in Turner syndrome.

Dissecting aortic aneurysm associated with congenital bicuspid aortic valve.

Among 119 cases of fatal dissecting aneurysm of the aorta, exclusive of those iatrogenically caused or associated with arachnodactyly or aortic stenosis, there were observed 11 cases of congenital bicuspid aortic valve (9%). The ages ranged from 17 to 69 years, five of the patients being 29 years old or younger. Among the latter, three had coarctation of the aorta and one had Turner's syndrome without coarctation. In one of the older patients, aortic insufficiency was present. Hypertension was either established or inferred from cardiac weight in 73% of the cases. In each case, cystic medial necrosis of the aorta was present. Prolapse of valves other than the aortic was observed in 45% of the cases with bicuspid aortic valve. Compared to an estimated incidence of bicuspid aortic valve of about 1 to 2% in the population, the high incidence among subjects with dissecting aneurysm suggests a causative relationship between bicuspid aortic valve and aortic dissecting aneurysm.