Definition
• A congenital malformation resulting in the formation of an abnormal aortic valve with two functional but unequal-sized cusps instead of the normal three cusps
Pathogenesis
• Abnormality in valvulogenesis causes fusion of two adjacent cusps to form a single aberrant cusp. It may be associated with coarctation of the aorta, patent ductus arteriosus, and left main coronary stenosis
• Can be associated with a deficiency or abnormality in NOTCH1, a gene encoding a single-pass transmembrane receptor responsible for developmental cell fate decisions
• The valve is not functionally stenotic at birth or in early adult life but is susceptible to acquired fibrosis and calcification under increased amounts of hemodynamic stress, causing valvular disease in the sixth and seventh decades
• Is associated with accelerated degeneration of the aortic media, resulting in structural weakness of the aortic wall leading to aneurysm, similar to patients with Marfan syndrome
Clinical features
Epidemiology
• Most common congenital anomaly; affects 1% to 2% of the population in the United States; male to female ratio, 2:1
Presentation
• Is usually asymptomatic and causes no hemodynamic problems for the first few decades of life
• Patients with a BAV may present with a murmur in the right second intercostal space. Most common abnormal sound heard is a systolic ejection click in all phases of respiration. Can be confirmed with an echocardiogram and MRI
• About 30% of individuals may have complications; 50% are associated with aortic coarctation
• Presents when valve becomes calcified, leading to aortic stenosis in half, aortic regurgitation in one third, and mixed lesions in younger patients
Prognosis and treatment
• Asymptomatic diagnosed cases require careful follow-up for morphological changes in the valve
• Patients may require valve replacement in third or fourth decade of life. Ross procedure may be performed
• Prophylactic antibiotics are recommended for patients with increased risk of endocarditis
• BAV malformations show familial clustering; therefore, genetic testing should be performed for family counseling
Pathology
Gross
• Most cases are seen with one complete line of coaptation and a low raphe between two conjoined cusps, resulting in one larger and one smaller cusp. Complications may include aortic stenosis or regurgitation, infective endocarditis, and aortic dilation (aneurysm)
• Thickening of the cusps occurs with variable degrees of calcification, which can be deforming and bulky
• Commissures may be located anywhere around the circumference of the sinus aorta but most often are medial and lateral with one coronary artery arising from each sinus
• Left ventricular hypertrophy may be present
Histology
• Nonspecific histologic findings do not contribute to the diagnosis
• In a stenotic BAV, the deforming amorphous calcific masses are separated by a hyalin matrix
• The distal end of the raphe joining the two segments of aberrant cusp shows mild cellular proliferation, likely related to hemodynamic changes
Immunopathology/special stains
• Not contributory
Main differential diagnoses
• Acquired: rheumatic heart disease, bacterial endocarditis
• Senile aortic stenosis of normal valve with three cusps
• Aortic insufficiency, idiopathic
• Congenital: unicuspid and quadricuspid valves that also lead to similar complications but are exceedingly rare