**2. Diagnosis**

**Figure 2.** The classification and incidence of BAVs.

have different dimensions [28]

338 Calcific Aortic Valve Disease

ure of the valve or aortic dissection.

**1.3. Genetics**

The site of cusp fusion can have effects on the prognosis of BAV [27], with the suggestion that type 1 BAVs are more likely to stenose as adults while type 2 valves will have complica‐ tions at a younger age. The fused valve leaflet in BAV is actually smaller in area. Valvular incompetence is usually caused by the redundancy of one cusp, since the two cusps usually

The coronary anatomy can be abnormal. Most patients with BAV disease have a left dominant coronary circulation [29]. This left coronary can arise from the pulmonary artery. The left main can also be up to 50% shorter than in normal in up to 90% of cases. This is an important consid‐ eration for any aortic valve surgery. The commonest abnormality associated with BAV is dila‐ tation of the thoracic aorta, also known as aortopathy. This is thought not only to be due to the altered flow in the aorta, but also due to cellular structural abnormalities including decreased

The other abnormality found in conjunction with BAV disease is coarctation of the aorta. [22,31]. The presence of coarctation and a poor result from repair can lead to more rapid fail‐

BAV is an inheritable disorder, with a family recurrence rate of approximately 35% [33]. Re‐ cent clinical studies have reported a 9% prevalence of BAV in first-degree relatives of pa‐

BAV is likely due to mutations in different genes with dissimilar patterns of inheritance [33]. The first genetic cause of BAV is Anderson syndrome, which is reported to be a result of mutations in the potassium channel gene KCNJ2 (chromosome 17q24.3)], whereas it clinical‐ ly presents as ventricular arrhythmias, periodic paralysis, and scoliosis [36]. Another muta‐ tions in a gene called NOTCH1(gene map locus 9q34.3), a transmembrane receptor that has a role in determining cell outcome in organogenesis, were noted in two families with BAV [37]. Regions 18q, 5q, and 13q are reported to contain genes responsible for BAV and/or as‐ sociated cardiovascular malformations [38,39]. The region 10q contains the ACTA2 gene,

tients with BAV which was the estimated population prevalance of 1-2% [33-35].

fibrillin, causing smooth muscle cell detachment, and cell death [30].

Clinical findings are usually limited to auscultation with most patients having an ejection systolic murmur heard loudest at the apex [47]. The S1 usually is normal but sometimes may be associated with ejection click. The S2 is soft, and when aortic stenosis is present, S2 occurs simultaneously with P2. In aortic stenosis, an ejection systolic murmur is heard in the left second intercostal space but may also be transmitted to the carotid arteries. If aortic incom‐ petence is present, a diastolic murmur of aortic regurgitation may be heard.

The electrocardiogram is usually normal; and ECG changes are not specific in patients with BAV: left ventricular hypertrophy, atrial enlargement, and arrhythmias may be present.

The mainstay of diagnosis is echocardiography (transthoracic or transoesophageal) which can provide a definitive diagnosis in the majority of patients [ 92% sensitivity and 96% spe‐ cificity) [48,49]. Transesophageal echocardiography (TEE) is also very important for evaluat‐ ing the aortic valve and thoracic aorta, whereas the sensitivity and specifity of multiplane technique for assessing aortic valve morphology is high [13].

The parasternal short axis view allows for direct visualization of the valve cusps. In this view the normal triangular opening shape is lost, becoming more "fish mouth-"like in ap‐ pearance, more similar to the mitral valve. This is especially pronounced in systole, as in di‐ astole the raphe can appear similar to a commissure of the third cusp. Differentiating severe bicuspid aortic stenosis from severe other aortic stenosis can also be difficult. In order to es‐ tablish the diagnosis, the valve must be visualized in systole in the short-axis view. In the long-axis view, the valve often has an eccentric closure line and there is doming of the leaf‐ lets. If there is uncertainty in diagnosis, a TEE can improve visualization of the leaflets [50].

For BAV associated with stenosis, mean gradient and maximal flow velocity should be measured, but when regurgitation is present, the effective regurgitant area and Doppler jet size should be evaluated. For asymptomatic patients with aortic stenosis, echocardiography is recommended for evaluating disease progression. In asymptomatic patients, TTE recom‐ mended: every year for severe aortic stenosis, ever 1-2 years for moderate aortic stenosis and every 3-5 years for mild aortic stenosis [51].

Symptoms associated with aortic stenosis are angina pectoris, syncope, and congestive heart failure. The most common complication of aortic stenosis is congestive heart failure sympto‐ matically presented with dyspnea, which is a result of combined diastolic and systolic dys‐ function [56]. Angina pectoris occurs in patients with severe aortic stenosis and in those who

The Bicuspid Aortic Valve http://dx.doi.org/10.5772/52567 341

Syncope is another common symptom in patients with BAV. Syncope reflects the cerebral hypoperfusion caused by the inability to increase stroke volume during physical activity.

The clinical presentation in patients with BAV and presence of other cardiac congenital de‐ fects depends from structural complexity of the heart. In patients with interventricular sep‐ tal defects, the clinical presentation depends on the size of the defect area and the grade of aortic stenosis. If the interventricular defect is small, the patient may be asymptomatic, but when the interventricular defect is large, cardiac output will decrease and Eisenmenger syn‐

Two large recent series reported that clinical course of unoperated patients with BAV de‐ pends on age, stenosis, and aortic incompetence. The severe aortic stenosis, and severe aortic incompetence in older patients increases the risk of primary cardiac events including cardiac death. Both these studies suggest that intervention on the basis of early symptoms or incipi‐

The natural history of BAV has been evaluated several cohort studies. It is known to be vari‐ able and of course somewhat dependent on associated abnormalities. It can range from se‐ vere aortic stenosis in childhood to asymptomatic disease until old age. There have indeed been incidental findings of a minimally calcified BAV in patients in their 70s.More common‐ ly however [in around 75% of patients] there is progressive fibrocalcific stenosis of the valve eventually requiring surgery. This usually leads to presentation in middle age only around

The prevalence of fibrosis, cystic medial necrosis, elastic fragmentation, and inflammation has been shown to be significantly higher in patients with fusion of the left coronary and right coronary cusps. fusion of the left coronary and right coronary cusps was associated with a larger aortic root diameter and a smaller aortic arch,than was fusion of the right coro‐ nary and non-coronary cusps. Another study demonstraed that fusion of the right coronary and non-coronary cusps correlated with the more rapid growth of ascending aortic diameter

There have been a couple of studies looking at long-term followup of patients with unoper‐ ated BAV. A cohort of 212 asymptomatic patients with BAV were found to have the same 20-year survival rate as the normal population but an increased frequency of cardiac events including aortic valve surgery, ascending aorta surgery and any other cardiovascular sur‐ gery. Predictive factors for cardiovascular events were found to be age ≥50 years and valve degeneration at diagnosis while baseline ascending aorta ≥40 mm independently predicted surgery for aorta dilatation. Another study [64] 642 patients were followed up for a mean of 9 years, again with a 10-year survival rate similar to the normal population [96%]. One or more primary cardiac events occurred in 25% including cardiac death in 3, intervention on

ent cardiac dysfunction may decreases the mortality of patients with BAV [57,58].

2% of children have clinically significant BAV disease [59].

in the pediatric population [60-63].

do not have coronary artery disease; it may be a result of ventricular hypertrophy.

drome will develop.

In patients with poor acustic window, cardiac magnetic resonance (MRI) and multidetector computed tomography are useful for measuring the aortic valve area and is an alternative method to echocardiography in selected cases. MRI especially will enable views of the valve to be obtained without interference from calcification. It also allows for excellent assessment of the aorta. A recent study of 123 patients with confirmed BAV found that 10% of the pa‐ tients were misidentified as having a tricuspid valve using transthoracic echo and 28% had a nondiagnostic study, in comparison to 4% being misidentified as having a tricuspid valve by MRI and 2% having a non-diagnostic study [52].

The current guidelines suggest that cardiac magnetic resonance imaging or cardiac comput‐ ed tomography is reasonable in patients with BAVs when aortic root dilatation is detected by echocardiography to further quantify severity of dilatation and involvement of theas‐ cending aorta (Clas IIa; Level of Evidence: B)[53].
