AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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• Clinical
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• Follow-up
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Background

Sir William Osler was one of the first to recognize the bicuspid aortic valve as a common congenital anomaly of the heart.¹ Leonardo da Vinci recognized the superior engineering advantages of the normal trileaflet valve.² However, bicuspid aortic valve is mentioned only briefly in many pediatric and cardiology textbooks.

Definition

The normal aortic valve has 3 equal-sized leaflets or cusps with 3 lines of coaptation. A congenitally bicuspid aortic valve has 2 functional leaflets. Most have one complete line of coaptation. Approximately half of cases have a low raphe. Stenotic or partially fused valves caused by inflammatory processes, such as rheumatic fever, are not included.

Embryology

The embryonic truncus arteriosus is divided by the spiral conotruncal septum during development. The normal right and left aortic leaflets form at the junction of the ventricular and arterial ends of the conotruncal channel. The nonseptal leaflet (posterior) cusp normally forms from additional conotruncal channel tissue. Abnormalities in this area lead to the development of a bicuspid valve, often through incomplete separation (or fusion) of valve tissue.³

Bicuspid aortic valve is often observed with other left-sided obstructive lesions such as coarctation of the aorta or interrupted aortic arch, suggesting a common developmental mechanism.⁴ Specific gene mutations have been isolated.⁵ 

Anatomy

The bicuspid valve is composed of 2 leaflets or cusps, usually of unequal size.^{6, 7}The larger leaflet is referred to as the conjoined leaflet. Two commissures (or hinge points) are present; usually, neither is partially fused. The presence of a partially fused commissure, which has also been called a high raphe, probably predisposes toward eventual stenosis. At least half of all congenitally bicuspid valves have a low raphe, which never attains the plane of the attachments of the two commissures and never extends to the free margin of the conjoined cusp. Redundancy of a conjoined leaflet may lead to prolapse and insufficiency.⁸

Valve leaflet orientation and morphology can vary. A recent surgical study showed conjoined leaflets in 76% of specimens.⁹ Of these, fusion of the raphe was noted between the right and left cusps in 86%, and fusion was noted between the left and noncoronary cusps in only 3%. Of the valves without raphes, more than 30% of the leaflets were unequal in size.

Coronary arteries may be abnormal.⁷ A left-dominant coronary system (ie, posterior-descending coronary artery arising from the left coronary artery) is more commonly observed with bicuspid aortic valve. Rarely, the left coronary artery may arise anomalously from the pulmonary artery. The left main coronary artery may be up to 50% shorter in patients with a bicuspid aortic valve. Occasionally, the coronary ostium may be congenitally stenotic in association with bicuspid aortic valve.

The aortic root may be dilated.¹⁰ This dilatation has some similarities to the dilatation of the aorta seen in Marfan syndrome.^{11, 12} The dilatation may involve the ascending aorta (most commonly) but may also involve the aortic root or transverse aortic arch.^{13, 14}

Pathophysiology

With degeneration of aging valves, sclerosis and calcification can occur. The changes are similar to those in atherosclerotic coronary arteries. The bicuspid valve may also be completely competent, producing no regurgitant flow. However, redundancy and prolapse of cusp tissue can lead to valve regurgitation. Complications arise in as many as one third of patients over their lifetimes;¹⁵ this disorder, therefore, deserves close attention and medical follow-up.

Valve morphology may be predictive of problems of stenosis, insufficiency, or both. Fusion along the right or left leaflets is less commonly associated with stenosis or insufficiency in children. This arrangement is much more common in patients with coarctation of the aorta, whose valves function adequately. Fusion along the right and noncoronary leaflets is more frequently associated with pathologic changes of stenosis or insufficiency in the pediatric population.¹⁶

Frequency

United States

Bicuspid aortic valves may be present in as many as 1-2% of the population. Because the bicuspid valve may be entirely silent during infancy, childhood, and adolescence, these incidence figures may be underestimated and are not generally included in the overall incidence of congenital heart disease.

International

Incidence does not appear to be affected by geography.

Race

A recent report suggests much lower than expected prevalence in African-Americans.¹⁷

Sex

The male-to-female ratio is 2:1 or greater. Sex is not a predictive variable in the natural history of bicuspid aortic valve. A recent prospective echocardiographic study in newborn infants showed a prevalence of bicuspid aortic valve in 7.1 per 1,000 male newborns versus 1.9 per 1,000 female newborns.¹⁸

Age

Bicuspid aortic valve may be identified in patients of any age, from birth through the 11th decade of life. It may be only an incidental finding at autopsy. Bicuspid aortic valve may remain silent and be discovered as an incidental finding on echocardiographic examination of the heart.

• Critical aortic stenosis and infective endocarditis may be considered relatively early sources of morbidity for patients with bicuspid aortic valve. Critical aortic stenosis may occur in infancy and may be associated with a bicuspid valve.
• Occasionally, bicuspid aortic valve is diagnosed after a patient has developed infective endocarditis with systemic embolization.
• Stenosis of a bicuspid aortic valve is more likely to develop in persons older than 20 years and is caused by progressive sclerosis and calcification. High levels of serum cholesterol have been associated with more rapidly progressive sclerosis of the congenitally bicuspid aortic valve. ¹⁹
• Children who develop early progressive, pathologic changes in the bicuspid aortic valve are more likely to develop valve regurgitation than stenosis. Bicuspid aortic valve was identified in 167 (0.8%) of 20,946 young Italian military conscripts. Of these, 110 were found to have either mild or moderate aortic insufficiency.

CLINICAL

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History

Patients with bicuspid aortic valves may be completely asymptomatic. About 30% of individuals with a bicuspid aortic valve develop complications.^{16, 20, 21} If symptoms are present, they relate to the development of aortic stenosis, aortic insufficiency, or both. Occasionally, a congenitally bicuspid aortic valve may be the cause of critical aortic stenosis, with symptoms of severe congestive heart failure developing in early infancy. This critical form of stenosis is more frequently associated with a unicommissural valve. In patients in whom a bicuspid aortic valve is observed in association with other types of left heart obstruction (coarctation or interrupted aortic arch), the bicuspid valve generally functions well, and symptoms are usually caused by the associated disorder.

• Inheritance: Although most cases of bicuspid aortic valve are sporadic, familial clusters have been identified, with incidence as high as 10-17% in first-degree relatives of probands.²² Increasing evidence suggests an autosomal-dominant inheritance pattern with variable penetrance, encompassing the entire spectrum of left heart obstruction (hypoplastic left heart syndrome, aortic stenosis, coarctation of the aorta) ²³
• Associated syndromes
• • Coarctation or interrupted aortic arch (bicuspid aortic valve is present in >50% of patients with these lesions)⁴
  • Williams syndrome (bicuspid aortic valve associated with supravalvular aortic stenosis occurs in 11.6% of cases)²⁴
  • Patent ductus arteriosus, also associated with hand anomalies²⁵
  • Turner syndrome (bicuspid aortic valve occurs in 30% of patients)²⁶

Physical

Because the bicuspid aortic valve is frequently a clinically silent condition, general examination findings may be normal.

• Typical features of Turner syndrome (eg, short stature in females with webbed neck and broad chest) or Williams syndrome (eg, elfin facies, mild retardation) may suggest the possibility of bicuspid aortic valve.
• Cardiac examination findings include the following:
• • The precordium is usually normal to palpation, and no evidence of cardiomegaly is present.
  • The first heart sound is unaffected. The second heart sound splits normally with inspiration, with absent or minimal outflow gradient. With increasing aortic stenosis gradient, the splitting of the second sound is less apparent or may be absent. With severe stenosis, the second sound is split paradoxically (ie, with expiration). This splitting differs from normal splitting of the first heart sound (ie, with tricuspid and mitral valve closures) in that normal splitting is best appreciated at the lower left sternal border and is a softer lower-pitched sound than the click of a bicuspid aortic valve.
  • The most common abnormal sound heard with bicuspid aortic valve is a systolic ejection click. This sound is actually a less-distinct, medium-pitched, short sound heard well at the apex with the diaphragm of the stethoscope. It is heard in all phases of respiration just after the first heart sound, and its timing does not vary with maneuvers (eg, hand-grip, Valsalva, squatting). The ejection sound may also be heard in the aortic area (upper right sternal border), where it takes on a brighter and sharper quality.²⁷
  • In contrast, the click of pulmonary valvular stenosis is intermittent (heard best during expiration) and located closer to the left sternal border. It is a bit less distinct than the aortic valve click. The click of mitral valve prolapse may also be heard at the apex but is softer, occurs later, and is less distinct than the bicuspid aortic valve click. The mitral prolapse click often varies in timing with changes in position or isometric handgrip and may be followed by the murmur of mitral regurgitation. Multiple showers of clicks are common, and the sound has been likened to crinkling cellophane.
  • Minimal or mild stenosis may produce a soft and fairly harsh ejection murmur at the upper right sternal border with possible radiation into the carotids. Increasing severity of stenosis produces a longer, louder, and harsher murmur with definite radiation into the carotids and possibly into the posterior shoulder. With more severe stenosis, a thrill may be felt in the suprasternal notch.
  • In the presence of a typical ejection click, the high-pitched sound of subtle aortic valve insufficiency may be heard at the third left intercostal space with the diaphragm of the stethoscope. Various maneuvers may be helpful in auscultation, including having the patient perform an isometric handgrip, having patients lean forward in a seated position (to bring the aortic area closer to the chest wall), and having patients hold their breath in expiration (also decreases the distance between the stethoscope and the left ventricle).²⁷

DIFFERENTIALS

Section 4 of 11  

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WORKUP

Section 5 of 11  

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Lab Studies

In the case of a child with bicuspid aortic valve and family history of hypercholesterolemia or early coronary artery disease, baseline cholesterol levels may be helpful in recommending dietary modification.

• Total and high-density lipoprotein (HDL) cholesterol or fasting lipid panel should be measured in children older than 3 years.
• Elevated low-density lipoprotein (LDL) cholesterol may accelerate sclerosis of the bicuspid aortic valve.¹⁹

Imaging Studies

• Chest radiography may reveal mild prominence of the ascending aorta in the posteroanterior projection along the superior right heart border. Left ventricular enlargement implies progressive aortic valve insufficiency. Chest radiography is generally not helpful as a screening tool for bicuspid aortic valve.
• Two-dimensional echocardiography provides accurate confirmation of a bicuspid aortic valve.²⁸
• • Imaging can show the bicuspid aortic valve in multiple planes. Most important information is obtained from the parasternal long-axis and short-axis views.
  • The long-axis view reveals the typical systolic doming due to limited valve opening. An approximation of valve orifice diameter can be obtained at peak systole. This view is also important for sizing the sinus of Valsalva, sinotubular junction, and ascending aorta.
  • The short-axis view is used to examine commissures, leaflet morphology, mobility, and the presence or absence of a low raphe. The diameter or area of the valve opening is generally overestimated in this view because the true orifice usually lies above this plane. The bicuspid valve typically looks like a fish's mouth on opening.
  • Doppler measurements of peak and mean systolic velocities and gradients can be recorded from the apical 5-chamber, the suprasternal, or the high right parasternal views. Doppler signal should be lined up as closely as possible and parallel to the jet to provide accurate estimates of flow velocities. Estimates of flow velocity from the apical view can sometimes be improved by moving the transducer more medially toward the sternum.
  • Parasternal long-axis and short-axis views can also be used for color Doppler studies, which evaluate for aortic insufficiency. The severity of aortic valve insufficiency can be assessed by several methods. One of the simplest and most reliable is to measure the insufficiency jet diameter at the aortic valve annulus and compare this diameter to the annulus diameter.
  • False-positive diagnosis of bicuspid aortic valve may arise from incomplete demonstration of all 3-valve closure lines. The typical normal (trileaflet) aortic valve shows a rotated Mercedes sign on closure. The bicuspid valve may not be recognized if a high raphe is observed with valve closure.
• Angiography²⁹
• • The bicuspid aortic valve is viewed best in the anteroposterior 30º right anterior oblique (RAO) projection. Injection is into the left ventricle and also into the aortic root.
  • Angiography is not the primary diagnostic method to diagnose a bicuspid aortic valve.
  • Typical finding is systolic doming of the valve margins due to incomplete opening.
  • Aortic insufficiency can be looked for on the aortic root injection.
• MRI: MRI is generally not helpful for the diagnosis of bicuspid aortic valve alone but may be helpful for complete assessment of the thoracic aorta, particularly in cases of coarctation, Turner syndrome, or Williams syndrome.
• Transesophageal echocardiography may be necessary to define valve commissures and vegetations in adolescents or young adults in whom bicuspid aortic valve is suspected on clinical grounds (particularly those with symptoms or findings that suggest infective endocarditis).²⁸

Other Tests

• Electrocardiography
• • ECG findings are generally normal for an isolated bicuspid aortic valve without stenosis or insufficiency.
  • Progression of stenosis or insufficiency leads to left atrial enlargement and left ventricular hypertrophy.
• Testing in family members
• • Two-dimensional echocardiography is recommended as a screening tool for the offspring and first-degree relatives (especially males) of patients identified as having a bicuspid aortic valve because a high recurrence rate (as much as 12-17%) has been shown in several families.³⁰

TREATMENT

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Medical Care

No specific medical care is required for individuals with bicuspid aortic valve unless they have progressive deterioration or infection. Serial follow-up evaluations are important for early recognition of potential complications (valve insufficiency, valve stenosis, progressive aortic root dilation) and the prevention of possible bacterial endocarditis.

Surgical Care

Surgery specifically for bicuspid aortic valve is not necessary unless progressive complications ensue (valve insufficiency, valve stenosis, progressive aortic root dilatation, possible bacterial endocarditis).

• The patient with known bicuspid aortic valve no longer requires antibiotic prophylaxis for invasive dental or noncardiac surgical procedures.³¹ If endocarditis has occurred on a bicuspid aortic valve, antibiotic prophylaxis is recommended.
• For noncardiac procedures, preoperative cardiac evaluation may be appropriate, particularly for patients with aortic stenosis or insufficiency. The patient with simple, uncomplicated bicuspid aortic valve should not require special anesthetic precautions, other than bacterial endocarditis prophylaxis, when appropriate.

Diet

Because hypercholesterolemia and other coronary artery disease risk factors may accelerate the sclerosis and deterioration of a congenitally bicuspid aortic valve, a heart-healthy diet is recommended for all patients, not only those with recognized risk factors. This diet should limit fat calories to no more than 30% of total calories. Calories from saturated fats should be limited to no more than 10% of total.

Activity

Patients with normally functioning bicuspid aortic valves (ie, no stenosis or insufficiency) do not require activity restrictions. They may participate in organized competitive sports activities after echocardiography or MRI to assess for dilated aorta.³²

• Patients who develop valve insufficiency or stenosis from a congenitally bicuspid aortic valve may require restrictions from strenuous competitive sports.³³
• Patients with aortic valve insufficiency should avoid strenuous isometric activity, such as weight lifting, rope climbing, and pull-ups.

MEDICATION

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Patients with bicuspid aortic valve are at increased risk for infective endocarditis. Prophylactic antibiotics are no longer required for dental or surgical procedures as recommended by the American Heart Association but are recommended to prevent recurrence if an episode of endocarditis has occurred.³¹ For more information, see Antibiotic Prophylactic Regimens for Endocarditis.

FOLLOW-UP

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Complications

Overall complication rates in patients with bicuspid aortic valves vary.¹⁵ In general, bicuspid aortic valve may be a common reason for acceleration of the normal aging process (eg, valve sclerosis, calcification). Four specific complications are related to the congenitally bicuspid aortic valve.

• Aortic stenosis
• • Sclerosis of the bicuspid aortic valve generally begins in the second decade of life, and calcification becomes more concerning during and after the fourth decade of life.²¹ The presence of coronary risk factors (eg, smoking, hypercholesterolemia) may accelerate these processes.
  • Approximately 50% of adults with severe aortic stenosis have a congenitally bicuspid valve.
  • Historically, rheumatic fever was the most common cause of aortic stenosis. With significantly decreasing incidence of rheumatic fever in developed nations, bicuspid aortic valve is the most common cause of aortic stenosis in adults and is probably the most common etiology of valve insufficiency as well. Acute rheumatic fever and its recurrences are still a major problem in developing countries, and, in these areas, long-term effects of rheumatic fever are still more significant than bicuspid valve in the etiology of aortic stenosis and insufficiency. Rheumatic aortic valve damage can be confirmed only at surgery or autopsy by the presence of Aschoff bodies.
• Aortic insufficiency
• • Most cases of severe aortic insufficiency are related, either directly or indirectly, to a congenitally bicuspid valve.
  • Numerous factors may contribute to development of aortic valve insufficiency. These include cusp prolapse, erosion of irregular commissure lines, aortic root dilatation (particularly at the sinotubular junction or supra-aortic ridge), infective endocarditis, and systemic hypertension (particularly with coarctation).
• Bacterial (eg, infective) endocarditis
• • The risk of developing infective endocarditis on a bicuspid aortic valve is 10-30% over a lifetime.
  • Bicuspid aortic valve is the second most common congenital etiology for infective endocarditis in infants and children;³⁴ overall, approximately 25% of endocarditis infections develop on a bicuspid valve.
• Aortic root dissection
• • Findings on histologic studies of the aortic root in individuals with bicuspid aortic valve are controversial.³⁵ Enlargement of the root is often attributed to poststenotic dilatation. However, the root may dilate without significant valve stenosis, and abnormal histology with broken elastic fibers and other findings suggestive of Marfan syndrome has been identified in numerous studies. ¹²
  • The risk of aortic root dissection is much higher for individuals with Marfan syndrome (approximately 40%) than for those with bicuspid aortic valve (approximately 5%). However, because bicuspid aortic valve is more prevalent in the general population, this disorder is more commonly associated with aortic root dissection.

Prognosis

• Overall prognosis for the individual with bicuspid aortic valve is good. Reviews and reports in the past have emphasized the fairly benign course for patients with bicuspid valves. However, more recent reports on the natural history of these valves suggest numerous more serious problems and an acceleration of normal valvular wear and tear. These problems may not develop until adulthood. Routine and regular follow-up for the child or adolescent with bicuspid aortic valve is recommended.

Patient Education

• Patient and family education should emphasize the fairly benign course for the child with bicuspid aortic valve.
• Older children and adolescents should begin to be made aware of the accelerated aging processes (ie, progressive stenosis), with particular attention to coronary risk factors.
• The importance of bicuspid aortic valve as a potential substrate for infective endocarditis should be emphasized. Good oral and dental hygiene is important.
• Most young individuals with bicuspid aortic valve should not require restrictions in physical activity or sports participation, unless they have stenosis or insufficiency. Routine examination is recommended prior to sports participation at least once.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• The bicuspid aortic valve may not be recognized as a source for emboli in cases of unexplained fever and focal CNS deficits.

Special Concerns

• Pregnancy in women with bicuspid aortic valve should pose no special concerns unless complications of progressive aortic stenosis or aortic root dilation occur.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Bicuspid aortic valve with unequal cusp size. Note eccentric commissure and raphe.
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Media type:  Image

Media file 2:  Parasternal long-axis echocardiogram showing doming of a bicuspid aortic valve.
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Media type:  Echo

Media file 3:  Parasternal short-axis echocardiographic view in diastole, showing bicuspid aortic valve with nearly equal cusp size and right-left orientation of the commissure. Note the 2 color signals showing minimal aortic insufficiency.
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Media type:  Echo

Media file 4:  Two-dimensional echocardiogram of typical bicuspid aortic valve in diastole and systole. Valve margins are thin and pliable and open widely, creating the fishmouth appearance.
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Media type:  Echo

Media file 5:  Long-axis and short-axis transthoracic echocardiograms showing a bicuspid aortic valve. In diastole, hammocking (prolapse) of the valve cusps occurs. The short-axis view shows the irregular sclerotic margins. This type of bicuspid valve is the most commonly replaced, typically because of insufficiency.
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Media type:  Echo

Media file 6:  Basilar oblique transesophageal image showing congenitally bicuspid aortic valve with vegetation (due to Streptococcus viridans endocarditis).
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Media type:  Echo

REFERENCES

Section 11 of 11

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26. Sachdev V, Matura LA, Sidenko S, et al. Aortic valve disease in Turner syndrome. J Am Coll Cardiol. May 13 2008;51(19):1904-9. [Medline].
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28. Brandenburg RO Jr, Tajik AJ, Edwards WD, et al. Accuracy of 2-dimensional echocardiographic diagnosis of congenitally bicuspid aortic valve: echocardiographic-anatomic correlation in 115 patients. Am J Cardiol. May 15 1983;51(9):1469-73. [Medline].
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31. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. Oct 9 2007;116(15):1736-54. [Medline].
32. Stefani L, Galanti G, Toncelli L, et al. Bicuspid aortic valve in competitive athletes. Br J Sports Med. Jan 2008;42(1):31-5; discussion 35. [Medline].
33. De Mozzi P, Longo UG, Galanti G, Maffulli N. Bicuspid aortic valve: a literature review and its impact on sport activity. Br Med Bull. 2008;85:63-85. [Medline].
34. Brook MM. Pediatric bacterial endocarditis. Treatment and prophylaxis. Pediatr Clin North Am. Apr 1999;46(2):275-87. [Medline].
35. Parai JL, Masters RG, Walley VM, et al. Aortic medial changes associated with bicuspid aortic valve: myth or reality?. Can J Cardiol. Nov 1999;15(11):1233-8. [Medline].

Article Last Updated: Nov 10, 2008