Alan S. Pearlman, MD, Division of Cardiology, Box 356422, Health Sciences Building, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195; e-mail: email@example.com
A 23-year-old man presented for cardiac evaluation following an abnormal chest radiograph. His employer had required purified protein derivative (PPD) testing, the results of which were positive. A chest radiograph was obtained and revealed normal lungs but an enlarged ascending aorta. For that reason, the patient was referred for further cardiovascular evaluation. He was a competitive cyclist without exercise limitation, was otherwise asymptomatic, and had no medical history. His cardiac examination findings had always been normal by his recollection. Physical examination revealed a fit man in no distress. His blood pressure was 105/60 mm Hg and heart rate was 45 beats per minute. The examination results were entirely normal. Electrocardiography demonstrated sinus bradycardia and minimal voltage criteria for left ventricular hypertrophy.
Despite the absence of symptoms and signs of heart disease, an echocardiogram was obtained (largely because of the enlarged aorta on radiography). The echocardiogram demonstrated a normally functioning bicuspid aortic valve (Figure 1). The ascending aorta was enlarged, with a maximal dimension of 4.0 cm, and a suggestion of aortic coarctation was noted by 2-dimensional echocardiographic imaging and Doppler evaluation of the aortic arch and proximal descending thoracic aorta. Subsequently, cardiac magnetic resonance imaging (MRI) confirmed the aortic dimensions, documented mild coarctation, and demonstrated a bicuspid valve (Figure 2).
Aortic valve disease is common and may affect patients of all ages. Patients with abnormal valves are at increased risk for developing hemodynamically significant stenosis or insufficiency during their lifetime. In patients with congenitally abnormal valves, the age and hemodynamic abnormality at presentation can provide clues to the underlying valve structure. In addition, the type of congenitally abnormal valve provides prognostic information about the expected course and the presence or absence of coexistent aortic abnormalities.
The normal aortic valve has 3 leaflets, but leaflet numbers may vary in congenitally abnormal valves. Congenitally abnormal aortic valves may be unicuspid, bicuspid, or tricuspid or the valves may have ≥4 leaflets. While valve function is clearly the most important prognostic indicator, the number of valve leaflets can provide helpful clinical information. Echocardiography can reliably identify the number of leaflets1 and any hemodynamic abnormalities. Identifying the number of aortic valve leaflets is an important part of the echocardiographic evaluation of patients referred for murmurs, abnormal heart sounds, or known aortic valve disease.
Aortic stenosis is the most common reason for valve replacement in the United States, and the number of aortic valve replacements is rising. The majority of valve replacements are performed in patients 50 years and older, but aortic valve disease can affect patients of all ages. The age at presentation with aortic valve disease is a clue to the number of leaflets. Infants presenting with aortic stenosis in the first year of life typically have unicuspid valves. Children, teenagers, and young adults with aortic valve disease are more likely to have bicuspid aortic valves. In patients aged 50 to 70 years, aortic stenosis severe enough to warrant valve replacement is as likely to be secondary to a bicuspid valve as it is to be due to a trileaflet valve.2 In patients older than 70 years, stenosis due to calcific disease of a trileaflet valve is more common than bicuspid valve disease.2
The number of aortic leaflets is also a clue to the type of valve dysfunction. Children with unicuspid valves typically have severe stenosis and require intervention in infancy. Rarely, a unicuspid valve will be sufficiently functional to escape intervention until childhood or young adult years. Young patients with bicuspid valves may have normal valve function,3 but aortic insufficiency can affect 20% to 40% of patients with bicuspid aortic valves. As patients with bicuspid valves age, aortic stenosis becomes more prevalent and more of a concern than aortic insufficiency. Hence, most patients with bicuspid valves requiring surgical intervention at younger than 25 years have underlying insufficiency, whereas those with bicuspid valves requiring aortic valve replacement after the age of 40 years typically have aortic stenosis. Almost all patients with bicuspid aortic valves will require surgery at some time,3 and one older study estimates that 75% of patients with bicuspid valves will require aortic valve replacement before age 70.4 It is not clear how this rate of aortic valve replacement will change as more asymptomatic patients with bicuspid valves are identified by improved echocardiographic techniques.
During embryologic development, the normal aortic valve develops 3 commissures. If commissure development is aborted, the resulting aortic valve will have <3 cusps. Development of an additional commissure can also occur and will result in a valve with 4 cusps. Valves with an abnormal number of leaflets may not open appropriately, causing stenosis, or the leaflets may not coapt normally, resulting in regurgitation. Patients with structurally abnormal aortic valves can generally be expected to develop hemodynamically significant disease at some point in their lifetime.
Unicuspid valves are extremely rare, affecting <0.02% of the population.5 They result from aborted commissural development. The valve has a central, eccentric orifice with limited mobility of the leaflet tissue and doming of the valve during systole. In some cases, the leaflet tissue may also be thickened. The typical presentation of a unicuspid valve is that of severe stenosis in infancy, but rarely, a unicuspid valve may function sufficiently in infancy and not present symptoms until later childhood or adolescence.
Bicuspid aortic valves have 2 functional leaflets. As with unicuspid valves, aborted commissural development underlies development of a bicuspid valve. In these valves, 2 commissures develop normally, but the third does not. A thick ridge, referred to as a raphe, is often seen where the commissure should have developed. The typical anatomy is a 2-leaflet valve with a raphe in one of the leaflets. The leaflet orientation may be anteroposterior or right-left. The leaflets may be symmetric or asymmetric. Data are evolving regarding the prognostic significance of the leaflet orientation or symmetry of the leaflets. Some studies have shown the valve phenotypes to have a relationship to the rate of aortic sclerosis or stenosis progression, while other studies demonstrated differences in elastic properties of the aorta related to the underlying valve structure.6–8 A relationship between valve structure, coarctation, and valve function has been suggested.9
Bicuspid aortic valves are associated with 2 important conditions, both exemplified in the described patient. Ascending aortic dilation is common and may lead to aneurysm formation. The ascending aortic dilation is not caused by aortic valve dysfunction, but rather it is the result of abnormalities of the aortic media. In addition to aortic dilation, approximately 6% of patients with bicuspid aortic valve also have coarctation of the aorta.10 Conversely, up to 50% of patients with coarctation of the aorta have a bicuspid aortic valve.11 As a reflection of the arteriopathy that these disorders likely represent, 10% of patients with bicuspid valve and coarctation have intracranial aneurysms.12
Isolated quadricuspid valves are rare, affecting <0.02% of the population.5 Valves with >3 cusps may be seen in truncus arteriosus. Normally, the truncus arteriosus is divided into the aorta and pulmonary artery by the development of conotruncal ridges. Failure of the ridges to develop may result in a single arterial outflow. The aorta is large, and the pulmonary artery is small or absent. The branch pulmonary arteries may arise from the aorta. The abnormal truncal development also involves the semilunar valves. The single semilunar valve is associated with the aorta and may be structurally normal or may have between 4 and 6 cusps. Truncus arteriosus is identified in infancy, and patients must undergo surgical repair early in life to optimize long-term outcomes. The truncal valve is often insufficient and may require replacement in childhood.
When transthoracic echocardiography is used, the anatomy of the aortic valve is best seen in parasternal short-axis views. Unicuspid and bicuspid valves often have raphes representing the aborted commissural development. As a consequence, when a bicuspid valve is closed, it may appear to have 3 commissures and therefore 3 leaflets. The orifice of these valves is abnormal, however; careful observation of the valve in systole is needed to identify the number of cusps.1 Whereas a normal trileaflet valve opens fully, resulting in a large triangular or almost circular orifice, bicuspid valves open with an oval or “fish mouth” orifice (Figure 1). Unicuspid valves have a more eccentric, ovoid orifice that is teardrop shaped (Figure 3). Once a valve is heavily calcified and poorly mobile, determining the number of leaflets is very difficult.
On the other hand, the abnormal number of leaflets in quadricuspid valves will be best seen with the valve closed. When closed, the quadricuspid valve commissures give the appearance of an X (Figure 4). The opening of the valve will likely be abnormal and confirm the number of leaflets.
Although parasternal short-axis views provide optimal visualization of the valve, parasternal long-axis views may provide clues to the presence of a congenitally abnormal aortic valve. Bicuspid and unicuspid valves typically “prolapse” into the left ventricular outflow tract when closed, and they often have limited leaflet opening, which gives the appearance of valve “doming” during systole. In some patients, particularly children, subcostal views may also provide good short-axis images of the aortic valve leaflets. This alternative acoustic window may be helpful in adult patients with difficult parasternal views as well.
Because of the association of ascending aortic dilation with bicuspid valves, the proximal aorta must be carefully visualized. Parasternal and suprasternal notch views allow measurement of the aortic root and ascending aorta. This evaluation may also provide clues as to the number of leaflets, because ascending aortic dilation in the face of a minimally stenotic or insufficient valve should raise suspicion that the valve is bicuspid. In patients with calcified valves, ascending aortic dilation is common in patients with bicuspid valves but uncommon in trileaflet valves.13
Because of the association discussed above, any patient with a bicuspid valve should undergo echocardiographic evaluation for coarctation. The high prevalence of associated bicuspid aortic valve in patients with coarctation mandates a careful evaluation of the aortic valve leaflets in any patient with coarctation of the aorta.
Valve function is a clue to the likely number of leaflets. Severe stenosis in a very young patient with pliable valve tissue is more likely to result from a unicuspid valve. Severe insufficiency in a teenager with pliable thin leaflets is likely indicative of a bicuspid valve. Stenosis in a patient aged 40 to 60 years is likely caused by a bicuspid valve, whereas stenosis in a patient older than 70 years is more likely calcific stenosis of a trileaflet valve.
Alternative Approaches to Imaging
Although echocardiography typically is the first and often the only imaging modality needed to assess aortic valve structure and function, poor echocardiographic windows sometimes preclude accurate assessment of valve leaflets. In these cases, cardiac MRI can provide additional information about valve structure and function (Figure 2). In a patient with bicuspid aortic valve, cardiac MRI or computed tomography (CT) can provide additional imaging of the aorta, which echocardiography often cannot assess completely. Current guidelines suggest examining the aorta with MRI or CT if the aorta is not well visualized on echocardiography or dilation is seen that requires better characterization.14
Patients with different numbers of aortic leaflets will have different associated disorders and expected outcomes. Accurate assessment of the number of leaflets, which can usually be done with carefully performed transthoracic echocardiography, facilitates better counseling of patients regarding the likely course of their valve disease and allows for more appropriately tailored follow-up. On the other hand, the number of leaflets is less important than an accurate assessment of valve function. In elderly patients with calcified valves, debating the number of leaflets may be of academic interest, but it is less likely to impact overall prognosis and management in that group of patients.