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  Disease summary:

  
  
  
  
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    Bicuspid aortic valve (BAV) disease is the commonest congenital heart lesion, affecting approximately 1% to 2% of the population and is approximately three times more common in men.

    
    
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    BAV is typically nonsyndromic, but is seen with increased frequency in the Turner and potentially Loeys-Dietz syndromes.

    
    
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    BAV is usually an isolated cardiac lesion but is often seen in conjunction with coarctation of the aorta and other obstructive left-sided lesions (Shone complex, hypoplastic left heart syndrome).

    
    
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    Aortic stenosis (AS) develops in most patients with BAV. The incidence of AS increases with age and BAV is the commonest indication for aortic valve replacement in patients under 70 years old.

    
    
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    Aortic regurgitation (AI) and infective endocarditis are also more prevalent in BAV.

    
    
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    BAV is associated with an elevated risk of developing thoracic aortic dilation and aneurysms (TADA) and subsequent aortic dissection and rupture. In children, the risk of aortic aneurysm increases with age, indicating the progressive nature of aortic dilation.

    
    
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    Longitudinal echocardiographic monitoring is recommended for patients with BAV, both for development or progression of valvular stenosis or regurgitation, and also for ascending aortic dilation. If the ascending aorta cannot be well visualized with transthoracic echocardiography (TTE), either computed tomography (CT) or magnetic resonance angiography (MRA) should be performed.

  
  

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  Family history:

  
  
  
  
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    Familial involvement has been reported in 37% of patients with BAV. When familial disease is present, inheritance is autosomal dominant with variable penetrance.

    
    
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    There is an increased risk of aortic dilation in individuals with apparently normal tricuspid aortic valve who are first-degree relatives of patients with BAV.

    
    
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    Screening of first-degree relatives of probands with BAV is recommended and this is most commonly accomplished by transthoracic echocardiography.

  
  

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  Genetic factors:

  
  
  
  
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    Mutations in NOTCH1 have been identified in limited kindreds with BAV and aortic calcification.

    
    
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    Mutations in ACTA2 have been identified in kindreds with TADA, livedo reticularis, and BAV.

    
    
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    In the vast majority of cases, the genetic etiology of BAV has not been identified.

  
  

Diagnosis

The cusps or leaflets of the normally tricuspid aortic valve are named after the adjacent coronary ostia, right coronary cusp, left coronary cusp, and noncoronary cusp. Fusion of two cusps causes BAV. The most common BAV morphology involves fusion of the right and left coronary cusps (R-L fusion), followed by right and noncoronary cusp fusion (R-N fusion), whereas fusion of the left and noncoronary cusps is exceedingly rare.

Physical examination provides clues to the diagnosis, but BAV is usually diagnosed by TTE. Notably, a prominent raphe, or ridge, at the site of leaflet fusion may provide the false impression of three distinct leaflets when the aortic valve is visualized during diastole. Accordingly diagnosis rests on visualizing two, instead of three aortic leaflets during systole. Supporting features are systolic doming or diastolic prolapse of the aortic valve and an abnormal leaflet coaptation plane. Not infrequently, limited image quality can limit visualization of the aortic leaflets and obscure the diagnosis. Diagnosis may also be confirmed with transesophageal echocardiography, cardiac CT, or cardiac MRI.

Clinical Characteristics

The Development of Aortic Valve Dysfunction

AS is the most common manifestation of valvular dysfunction with BAV, with the majority of patients developing clinically relevant AS at some point. AS may be congenital (small valve orifice at birth) or, more commonly, develop due to an active process leading to valvular calcification and decreased mobility. AR is less common than stenosis and may result from redundant valve tissue, aortic root dilation, or infective endocarditis. There is an increased risk for development of infective endocarditis, likely related to turbulent flow and the consequent presence of a denuded valve surface allowing bacterial seeding.

Associated Anomalies

TADA is an important manifestation of BAV. Even in the absence of aortic dilation, there is evidence of abnormal aortic wall histology associated with BAV including increased apoptosis of vascular smooth muscle cells. Aortic pathology in patients with BAV and aortic aneurysms demonstrate findings consistent with what has historically been termed as “cystic medial necrosis,” namely fragmented elastic lamellae with increased basophilic ground substance with a paucity of vascular smooth muscle cells without evidence of inflammation. Similar to that seen with Marfan disease, there is altered matrix metalloproteinase activity, in a pattern different than what is seen with aortic aneurysms associated with tricuspid aortic valve. The prevalence of aortic disease varies by age group, anatomic aortic position, and definition of aortic dilation and aneurysm. Aortic dilation occurs most frequently at the ascending aorta (between the sinotubular junction and the right brachiocephalic artery), but also can affect the sinuses of Valsalva. The aortic arch, descending thoracic aorta, and abdominal aorta are typically spared.

There is a 6% lifetime risk of thoracic aorta dissection or rupture in BAV; ninefold greater than age matched individuals without BAV. The main risk factors for dissection are aortic size and rate of growth. Given the relative rarity of dissection, there are limited data on other independent predictors. Dissection related to BAV is associated with the same signs and symptoms as other causes of dissection and dissection appears to occur at similar aortic size on average as other causes of dissection. There are few data comparing outcomes between BAV and other causes of dissection.

While still relatively uncommon, there is an increased prevalence of coarctation of the aorta and hypoplastic left heart syndrome in patients with BAV. Conversely, approximately 50% of patients with coarctation of the aorta have BAV. There is also an increased prevalence of left dominant coronary circulation in BAV.

Dilation of the proximal pulmonary trunk and abnormalities of the pulmonary arterial wall are seen in patients with BAV, even those with a structurally normal pulmonary valve. This is of clinical significance when surgical repair with a Ross procedure (using the native pulmonary root and valve as a neoaorta/aortic valve) is considered; as these patients may be at increased risk for neoaortic dilation.

Emerging evidence suggests a risk of intracranial arterial aneurysms in BAV. Leaflet morphology is a predictor of associated anomalies and outcomes.

As shown in Fig. 26-1, the frequency of associated cardiac anomalies and major clinical outcomes appears to be influenced by leaflet morphology. Right noncoronary fusion (~25% of cases) is associated with a greater burden of valvular dysfunction, while fusion of the right and left coronary cusps (~75% of cases) is more highly associated with dilation of the aorta at the sinuses of Valsalva and coarctation of the aorta.