Bicuspid Aortic Valve: Genetic and Clinical Insights

AbstractBicuspid aortic valve (BAV) is the most common valvular congenital heart disease, with a prevalence of 0.5 to 2% in the general population. Patients with BAV are at risk for developing cardiovascular complications, some of which are life-threatening. BAV has a wide spectrum of clinical presentations, ranging from silent malformation to severe and even fatal cardiac events. Despite the significant burden on both the patients and the health systems, data are limited regarding pathophysiology, risk factors, and genetics. Family studies indicate that BAV is highly heritable, with autosomal dominant inheritance, incomplete penetrance, variable expressivity, and male predominance. Owing to its complex genetic model, including high genetic heterogenicity, only a few genes were identified in association with BAV, while the majority of BAV genetics remains obscure. Here, we review the different forms of BAV and the current data regarding its genetics. Given the clear heritably of BAV with the potential high impact on clinical outcome, the clinical value and cost effectiveness of cascade screening are discussed.

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The bicuspid aortic valve and related disorders

Sao Paulo Medical Journal ◽

10.1590/s1516-31802010000500010 ◽

2010 ◽

Vol 128 (5) ◽

pp. 296-301 ◽

Cited By ~ 7

Author(s):

Shi-Min Yuan ◽

Hua Jing

Keyword(s):

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Thrombus Formation ◽

Beta Blockers ◽

Ductus Arteriosus ◽

Treatment Strategies ◽

Hereditary Diseases ◽

Laboratory Findings ◽

Male Predominance ◽

Congenital Cardiac Malformation

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, affecting 1-2% of the population, with strong male predominance. Individuals may have a normally functioning BAV, and may be unaware of its presence and the potential risk of complications. However, they may easily develop aortic valve disorders: either stenotic or regurgitant, or both. Today, BAV is recognized as a syndrome incorporating aortic valve disorders and aortic wall abnormalities, including aortic dilation, dissection or rupture. Congenital or hereditary diseases such as ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, Turner's syndrome, Marfan's syndrome etc., may frequently be associated with BAV. Infective endocarditis and occasionally thrombus formation may develop during the lives of BAV patients. Elevated cholesterol or C-reactive protein may be seen in laboratory findings of these patients. Beta-blockers and statins are the possibilities for medical treatment, and aortic valve repair/replacement and ascending aorta replacement are indicated for patients with a severely diseased aortic valve and aorta. Rigorous follow-up throughout life is mandatory after BAV has been diagnosed. The aim of the present article was to describe the implications of BAV and its associated disorders, and to discuss diagnostic and treatment strategies.

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Bicuspid Aortic Valve in 2 Model Species and Review of the Literature

Veterinary Pathology ◽

10.1177/0300985819900018 ◽

2020 ◽

Vol 57 (2) ◽

pp. 321-331 ◽

Cited By ~ 1

Author(s):

Borja Fernández ◽

María Teresa Soto-Navarrete ◽

Alejandro López-García ◽

Miguel Ángel López-Unzu ◽

Ana Carmen Durán ◽

...

Keyword(s):

Animal Models ◽

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Wide Spectrum ◽

Genetically Modified ◽

Type A ◽

Mouse Strains ◽

Genetic Modifiers ◽

Interspecific Differences ◽

Congenital Cardiac Malformation

Bicuspid aortic valve (BAV) is the most common human congenital cardiac malformation. Although the etiology is unknown for most patients, formation of the 2 main BAV anatomic types (A and B) has been shown to rely on distinct morphogenetic mechanisms. Animal models of BAV include 2 spontaneous hamster strains and 27 genetically modified mouse strains. To assess the value of these models for extrapolation to humans, we examined the aortic valve anatomy of 4340 hamsters and 1823 mice from 8 and 7 unmodified strains, respectively. In addition, we reviewed the literature describing BAV in nonhuman mammals. The incidences of BAV types A and B were 2.3% and 0.03% in control hamsters and 0% and 0.3% in control mice, respectively. Hamsters from the spontaneous model had BAV type A only, whereas mice from 2 of 27 genetically modified strains had BAV type A, 23 of 27 had BAV type B, and 2 of 27 had both BAV types. In both species, BAV incidence was dependent on genetic background. Unlike mice, hamsters had a wide spectrum of aortic valve morphologies. We showed interspecific differences in the occurrence of BAV between humans, hamsters, and mice that should be considered when studying aortic valve disease using animal models. Our results suggest that genetic modifiers play a significant role in both the morphology and incidence of BAV. We propose that mutations causing anomalies in specific cardiac morphogenetic processes or cell lineages may lead to BAV types A, B, or both, depending on additional genetic, environmental, and epigenetic factors.

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Serial evaluation of the thoracic aorta in patients with a bicuspid aortic valve: A magnetic resonance angiography study

VASA ◽

10.1024/0301-1526/a000019 ◽

2010 ◽

Vol 39 (2) ◽

pp. 140-144 ◽

Cited By ~ 1

Author(s):

Tutarel ◽

Meyer ◽

Lotz ◽

Westhoff-Bleck

Keyword(s):

Aortic Valve ◽

Thoracic Aorta ◽

Bicuspid Aortic Valve ◽

Aortic Root ◽

Innominate Artery ◽

Ascending Aorta ◽

Current Data ◽

Descending Aorta ◽

Valve Function ◽

A Prospective Study

Background: Bicuspid aortic valve (BAV) is associated with an arteriopathy leading to a progressive dilatation of the aortic root. Recent studies have shown that the whole thoracic aorta is affected by this arteriopathy. Longitudinal data regarding the progression of this arteriopathy in the whole thoracic aorta has not been reported before. Patients and methods: In this retrospective study 40 patients (mean age 28.5 ± 9.1 years) had 2 MR-angiographies (mean interval 37.1 ± 15.2 months). In 23 patients the aortic valve was regurgitant, in 1 stenotic, in 4 combined aortic stenosis / regurgitation was found, while in 12 the valve function was normal. Aortic diameters were measured at 6 different, standardized anatomical points. The influence of demographic and clinical parameters was assessed. Results: A significant increase of the diameter was observed at the aortic root (35.4 ± 5.6 mm → 39.1 ± 6.5 mm, p < 0.001), the ascending aorta (37.3 ± 8.0 mm → 39.5 ± 8.5 mm, p = 0.001), proximal to the innominate artery (29.4 ± 6.1 mm → 31.6 ± 6.8 mm, p = 0.008), and the descending aorta (20.2 ± 2.4 mm → 21.6 ± 4.2 mm, p = 0.03). There was no significant increase proximal (24.0 ± 5.7 mm → 24.6 ± 5.3 mm, p = 0.44) and distal to the left subclavian artery (21.4 ± 4.6 mm → 21.9 ± 4.5 mm, p = 0.19). These observations were independent of the presence of arterial hypertension, a previous operation, gender, and functional status of the aortic valve. Conclusions: The progressive dilatation of the aortic root and ascending aorta that can be observed in patients with BAV was not found in the more distal parts of the thoracic aorta with the exception of the descending aorta in this study. If the dilatation of the descending aorta bears any clinical significance can't be answered with the current data. A prospective study should be performed to confirm these results.

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Predictors of ascending aortic dilatation with bicuspid aortic valve: a wide spectrum of disease expression☆

European Journal of Cardio-Thoracic Surgery ◽

10.1016/j.ejcts.2006.12.006 ◽

2007 ◽

Vol 31 (3) ◽

pp. 397-405 ◽

Cited By ~ 200

Author(s):

Alessandro Della Corte ◽

Ciro Bancone ◽

Cesare Quarto ◽

Giovanni Dialetto ◽

Franco E. Covino ◽

...

Keyword(s):

Aortic Valve ◽

Bicuspid Aortic Valve ◽

Wide Spectrum ◽

Aortic Dilatation ◽

Disease Expression

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Bicuspid aortic valve outcomes

Cardiology in the Young ◽

10.1017/s1047951116002560 ◽

2016 ◽

Vol 27 (3) ◽

pp. 518-529 ◽

Cited By ~ 10

Author(s):

Inês Rodrigues ◽

Ana F. Agapito ◽

Lídia de Sousa ◽

José A. Oliveira ◽

Luísa M. Branco ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Dissection ◽

Confidence Interval ◽

Thoracic Aorta ◽

Bicuspid Aortic Valve ◽

Hazard Ratio ◽

Cardiac Events ◽

Term Survival ◽

Valve Dysfunction ◽

End Point

AbstractBackgroundBicuspid aortic valve is the most common CHD. Its association with early valvular dysfunction, endocarditis, thoracic aorta dilatation, and aortic dissection is well established.ObjectiveThe aim of this study was to assess the incidence and predictors of cardiac events in adults with bicuspid aortic valve.MethodsWe carried out a retrospective analysis of cardiac outcomes in ambulatory adults with bicuspid aortic valve followed-up in a tertiary hospital centre. Outcomes were defined as follows: interventional – intervention on the aortic valve or thoracic aorta; medical – death, aortic dissection, aortic valve endocarditis, congestive heart failure, arrhythmias, or ischaemic heart disease requiring hospital admission; and a composite end point of both. Kaplan–Meier curves were generated to determine event rates, and predictors of cardiac events were determined by multivariate analysis.ResultsA total of 227 patients were followed-up over 13±9 years; 29% of patients developed severe aortic valve dysfunction and 12.3% reached ascending thoracic aorta dimensions above 45 mm. At least one cardiac outcome occurred in 38.8% of patients, with an incidence rate at 20 years of follow-up of 47±4%; 33% of patients were submitted to an aortic valve or thoracic aorta intervention. Survival 20 years after diagnosis was 94±2%. Independent predictors of the composite end point were baseline moderate–severe aortic valve dysfunction (hazard ratio, 3.19; 95% confidence interval, 1.35–7.54; p<0.01) and aortic valve leaflets calcification (hazard ratio, 4.72; 95% confidence interval, 1.91–11.64; p<0.005).ConclusionsIn this study of bicuspid aortic valve, the long-term survival was excellent but with occurrence of frequent cardiovascular events. Baseline aortic valve calcification and dysfunction were the only independent predictors of events.

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Is raphe only an innocent bystander finding or a predictor of complications in bicuspid aortic valve patients? Experience of Italian REBECCA registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0059 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Bellino ◽

R Citro ◽

S La Carrubba ◽

I Fabiani ◽

P Faggiano ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Stenosis ◽

Bicuspid Aortic Valve ◽

Aortic Root ◽

Wide Spectrum ◽

Smoking Habit ◽

Ascending Aorta ◽

Innocent Bystander ◽

Type B ◽

Type 3

Abstract Background Bicuspid aortic valve (BAV) is the most common congenital heart disease, affecting 0.5%–2% of the general population. It is associated with valvular dysfunction (aortic stenosis and/or regurgitation, endocarditis) but also with a wide spectrum of aortopathy with unpredictable clinical presentations. The role of the raphe is still controversial. Methods The REgistro della Valvola Aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging is a retrospective/prospective, multicenter, observational registry, with definitive diagnosis of BAV. Anamnestic, demographic, clinical, and instrumental data are collected into dedicated software at first evaluation and during follow-up. Aortopathy was defined as: annulus ≥14 mm/m2; root ≥20 mm/m2; sino-tubular junction (STJ) ≥16 mm/m2; ascending aorta (AA) ≥17 mm/m2; it was classified in: type A, dilation of the ascending aorta; type B, dilation of the aortic root and the ascending aorta; and type C, isolated dilation of the aortic root. Patients were divided in two groups; those with raphe and those without. Results At December 2019, 800 patients with BAV (Male, 73.3%; M:F ratio 2.9; Mean Age at diagnosis 44±23 years) have been included in the registry. Prevalence of hypertension was 29%, diabetes mellitus 3%, smoking-habit 8%. We reported a majority (42.7%, 342) of patients with type 1, followed by type 2 (10.2%, 82) and type 3 (3.7%, 30). No gender differences were observed according to BAV phenotypes, while male gender was associated to higher prevalence of aortic valve regurgitation (p=0.0003). Moreover, in patients with raphe, aortic stenosis (49.8% vs 38.4%; p=0.014) and aortopathy (57.4% vs 46.1%; p=0.034) were significantly prevalent (see Table 1). Of note no difference about aortic regurgitation (62.8% vs 48.7%; p=0.064) between two groups were detected. At univariable logistic regression analysis the presence of raphe was significantly associated with aortopathy [OR: 1.57; 95% CI: 1.02–1.42; p=0.037] especially with Type B Aortopathy [OR: 0.55: 95% CI: 0.33–0.93: p=0.02]. Conclusion Preliminary data from Italian Multicenter REBECCA registry highlight that, in patients with BAV, the raphe is not an innocent bystander but a risk factor for aortic stenosis and type B aortopathy. Funding Acknowledgement Type of funding source: None

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Subtle Aortic Dissection in a Patient with Severe Aortic Regurgitation and Undiagnosed Bicuspid Aortic Valve: Case Report with a Literature Review

10.22541/au.161825143.36757661/v1 ◽

2021 ◽

Author(s):

Davorin Sef ◽

Stewart Brown ◽

Omar Jarral ◽

Azhar Hussain ◽

Elizabeth Haslam ◽

...

Keyword(s):

Aortic Valve ◽

Literature Review ◽

Aortic Dissection ◽

Aortic Regurgitation ◽

Bicuspid Aortic Valve ◽

Current Data ◽

Preoperative Imaging ◽

Severe Aortic Regurgitation ◽

Bentall Procedure ◽

Dismal Prognosis

A subtle aortic dissection can be challenging to detect despite the availability of multiple diagnostic modalities. Whilst rare, the inability to detect this variant of aortic dissection can lead to a dismal prognosis. We present an extremely rare case of a subtle aortic dissection with supraannular aortic root intimal tear and acute severe aortic regurgitation in a patient with a bicuspid aortic valve. Initial concerns were either aortic dissection or infective endocarditis. Despite advanced multimodality preoperative imaging, diagnosis was made intraoperatively and a Bentall procedure with a mechanical aortic valve was performed. As current data is limited, a literature review concerning subtle aortic dissection is provided.

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