Bicuspid Aortic Valve

Etiology

The bicuspid aortic valve can be sporadic or familial. Evidence supports that mode of inheritance for a familial bicuspid aortic valve is variable but it could be autosomal dominant.[1] Almost 20% to 30% of other family members have a bicuspid aortic valve.  

The exact mechanism of the bicuspid aortic valve is still unknown. There are different theories regarding its pathogenesis. One theory suggests that abnormal blood flow across the valve during a development phase results in incomplete separation of the valve. [2] Kappetein AP and et al. also investigated another theory according to which abnormal neural crest migration resulting in the fusion of valve cushions.[3] Some suggest the absence of endothelial nitric oxide synthetase causes bicuspid aortic valve.[4] 

Epidemiology

Bicuspid aortic valve occurs in 1-2% of the general population. Its prevalence has been increased after the advent of echocardiography. 50% to 75% patients with coarctation of the aorta have a bicuspid aortic valve.[5] It's also prevalent in other syndromes like Turner syndrome (30% of cases).[6] Similarly, 30% of cases of William syndrome and ventricular septal defect are also associated with it. It is also prevalent in some rare syndromes like Shone syndrome.[7]

Pathophysiology

The normal aortic valve consists up of three leaflet cusps. 

1. Right coronary cusp
2. Left coronary cusp
3. Non-coronary cusp

It named like this as they overlie on the sinuses from where the coronary artery arises with the same name. [8]

The bicuspid aortic valve comprises two cusps and a majority of the time it is unequal, rarely they are symmetrical which is a pure bicuspid with no raphe. Mostly, it is due to the fusion of the right and left coronary cusp, and this anomaly associated with coarctation of the aorta. It could be due to the fusion of the non-coronary cusp and right coronary cusp which associated with valvular abnormalities like aortic stenosis and aortic regurgitation.[9] Valvular abnormality mainly depends on the presence or absence of redundant tissue. Bicuspid valves in which there is predominantly no redundant tissue develop stenosis; in contrast, in the presence of redundant tissue, the predominant gained pathology is valvular incompetence.[10]

History and Physical

The presentation of the bicuspid valve is variable and varies depending on the degree of stenosis and/or insufficiency of the valve. The most benign pediatric presentation is without symptoms or features of valve dysfunction.  In this case, the physical examination may show a low-pitched systolic ejection murmur and ejection click. The young population often has an early ejection sound followed by a systolic ejection murmur. The ejection sound depends on the mobility of the valve so as the valve cusps become more immobile the ejection sounds diminish. The examination also depends on the severity of the valvular insufficiency. In mild to moderate aortic regurgitation ejection sound is definitely there but in severe aortic regurgitation the ejection sound usually absent. 

Evaluation

The evaluation of a bicuspid valve routinely includes an electrocardiogram and echocardiogram. If there is severe stenosis, the electrocardiogram can show left ventricular hypertrophy with increased voltages in the lateral precordial lead and potentially T-wave inversion, consistent with a strain pattern. The echocardiogram is the most common way to understand the features and function of a bicuspid aortic valve. 2D echocardiography will demonstrate where the fusion of the valve leaflets occur, systolic doming (can not visualize when extensive calcification present), an eccentric valve closure in the parasternal long-axis views, the demonstration of a single commissural line in diastole with the characteristic two cusps and two commissures, leaflet redundancy, presence of a raphe, eccentric valve closure in the parasternal short-axis views and can fairly reliable measurements of the ascending aorta.[11],[12]  

Doppler echocardiography can provide information on the degree of stenosis with a peak and mean gradient with the mean gradient correlating with invasive catheter measurements. Furthermore, Doppler measurements can be made to demonstrate the degree of insufficiency of the valve.  Rarely invasive cardiac catheter measurements are made for diagnostic purposes only but are usually reserved when an intervention is planned. CT scan and MRI imaging can be obtained to help make a more accurate measurement of the ascending aorta.  

2D echocardiography has a sensitivity of 78%, a specificity of 96%, and a predictive accuracy of 93%.[13]

Treatment / Management

The well-functioning bicuspid aortic valve requires periodic outpatient follow-up.  Families should be advised that the bicuspid aortic valve predictably will degenerate during one's lifetime. So far there is no medical intervention that can slow the progression of the bicuspid aortic valve into aortic stenosis or aortic regurgitation. 

All first-degree relatives of bicuspid aortic valve patients with aortopathy should be screened. Otherwise, there are no such recommendations to screen all family members.[14] One-time transthoracic echocardiography required in a patient known bicuspid aortic valve to evaluate its morphology, severity of aortic stenosis or aortic regurgitation if they are present, and the size of aortic sinuses and ascending aorta.[15](B2)

Bicuspid aortic valve with ascending aorta diameter of 4 cm needs periodic surveillance through echocardiography (if not visualized by it then aortic magnetic resonance angiography or CT angiography). If the size is over 4.5 cm, then annually echocardiography recommended by American Heart Association. 

Surgical intervention indications in a pediatric population;

• Peak-to-peak gradients over 50 mm Hg with EKG changes (ST- or T-wave changes) at rest or with exercise or who are interested in taking part in athletics
• Asymptomatic children with peak-to-peak gradients greater than 60 mm Hg

Gold standard surgical intervention in the pediatric population is valvuloplasty. 

In the bicuspid aortic valve population age greater than 18 years the indications of aortic valve replacement are the same as a tricuspid aortic valve but the bicuspid aortic valve population receiving aortic valve replacement is much younger so the decision of mechanical or bioprosthetic is a little challenging. Thirty percent of bicuspid aortic valve patients need aortic sinuses or ascending aorta surgery along with aortic valve replacement.[16] Current AHA guidelines recommend that if for any reason surgeon performing aortic valve replacement and the size of the root of the aorta is greater than 4.5 cm then replace the aortic root as well in the same surgery.[17](B2)

Differential Diagnosis

• Coarctation of the aorta

• Interrupted aortic arch

• Pediatric aortic arch insufficiency

• Pediatric Ebstein anomaly

• Pediatric mitral valve prolapse

• Pediatric rheumatic heart disease

• Pediatric sub valvar aortic stenosis

• Turner syndrome

• Valvar pulmonary stenosis

• Williams syndrome

Complications

The bicuspid aortic valve can lead to significant valvular dysfunction which could be aortic stenosis or aortic regurgitation. The risk of infective endocarditis is high among populations with a bicuspid valve. 

The bicuspid aortic valve is also associated with:

• Coarctation of aorta
• Ascending aortic dilatation 40% to 60%
• Aortic aneurysm