**7. Treatment strategies**

### **7.1. Medical treatment**

The systolic ejection murmur of the aortic stenosis, auscultated on the left side of the sternum, and the diastolic murmur of the aortic regurgitation, heard mainly on the apex, are highly valuable in the diagnosis. In the current area, transthoracic echocardiogram usually confirms the diagnosis of BAV disease. For the confirmation, the valve must be visualized in systole and diastole in the short axis view. The valve openings are fish-mouth shaped. Diastolic images can be misleading because the cusp fusion in the larger leaflet of a bicuspid valve may simulate a tri-leaflet valve in the closed position. It may be more difficult to make the diagnosis if there is an incomplete fusion between the cusps. The valve closure is usually

It may be difficult to make the diagnosis in the obese patients due to the nonqualified, blurred vision. In such cases, the diagnosis can be established by means of transoesaphagial echocar-

The clinical course of BAV patients is highly non-predictable. The factors determining the prognosis are older age, RN or RL BAV phenotype, flow dynamics (right-handed flow), male gender, elevated systolic blood pressure, smoking, presence of valvular and ventricular dysfunctions, aortic dilatation, endocarditis, high total cholesterol levels, valve degeneration score, and genetic predisposition [45, 69]. Aneurysm formation, aortic dissection, severe valvular dysfunction, and endocarditis are the most important causes of morbidity and mortality of BAV disease. AR is the most common complication in younger patients, more common in males, whereas AS is more common in elderly and females [45, 55]. In addition, RN BAV phenotype is strongly predictive of valve intervention when compared with RL BAV phenotype. RN BAV phenotype has a fourfold risk of time-related valve intervention compared with RL

Some BAV cases may present with severe stenosis or regurgitation especially in infants or children. Children who present with AS in infancy have more severe disease and poor outcomes. Fortunately, balloon valvuloplasty is the successful treatment of choice for severe AS

With respect to the BAV manifestations, it is estimated that only 1 in 50 children would have a clinically significant valve disease by adolescence. The majorities of BAV patients have relatively normal valve function and remain undiagnosed until 40 years of age, when stenosis develops because of leaflet calcification. In total, 53% of the BAV patients with isolated AS undergo valve replacement [65, 70, 71]. In the elderly population, AS is the most common presentation which causes 75% of patients to undergo surgery, while AR was the reason for intervention in only 13–16% of BAV patients [45, 72]. Asymptomatic adults without significant valve dysfunction enjoy excellent long-term survival with a 10- and 20-year survival rate of 97 and 90%, respectively, identical to the expected survival of the population matched for age and sex [73]. Mean follow-up of 15 years showed a 6.7% death ratio, 1.4% of which were related with the aortic valve endocarditis, 0.47% with AS, and 0.47% with AR. In total, 18.3% of these patients underwent aortic valve surgery, most of which were due to severe AS [73]. The 10-year survival rate of the asymptomatic young adults with BAV was found to be 96%.

diography (TEE) or cardiac MRI or computerized tomography (CT) imaging.

eccentric and the leaflets show doming in the long axis views.

**6. Clinical course**

110 Structural Insufficiency Anomalies in Cardiac Valves

BAV phenotype during childhood [39, 66].

in this age group because of very little calcification [70].

Beta-adrenergic blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers are the antihypertensive agents of choice. Beta-adrenergic blockers have the theoretical advantage of reducing aortic wall shear stress, whereas angiotensin receptor blockers have been shown to reduce the rate of aortic growth in patients with Marfan's syndrome [24]. The studies about the various treatment modalities are continuing vigorously.

#### **7.2. Intervention**

During childhood, insertion of a prosthetic valve is suboptimal because of the continuing growth of the child. Fortunately, at this stage, the aortic valve is usually not calcified and valvuloplasty can successfully disrupt the commissural fusion and relieve obstruction. Valvuloplasty is the interventional strategy of choice in children and in some young adults with BAV and AS [70].

#### **7.3. Surgical treatment**

Patients who have an aortic root or ascending aorta with a diameter of 45–50 mm may be considered for surgery only if they have high-risk features such as a family history of aortic dissection, rupture, or sudden death, and an aortic growth rate of more than 5 mm per year and if there is no need for valvular surgery [81]. Currently, aortic root surgery is not usually performed if the root measurement is <45 mm, or ratio of maximum ascending aorta area to body-height ratio is <10 cm<sup>2</sup> /m [82]. Guidelines recommend ascending aortic replacement in patients with BAV if the ascending aortic diameter is ≥50 mm. Concomitant aortic surgery is suggested if the diameter exceeds 45 mm [83]. Nonetheless, some authors have recommended ascending aorta surgery at 40 mm along with concomitant aortic valve regurgitataion (AVR), if the operation risk is low and expected survival is 1 decade or longer. Moreover, many surgeons consider reinforcing or replacing the ascending aorta at the time of valve surgery if there is an increased risk of further root dilation [84–86]. Aortic root dilatation may progress after AVR in the patients with pure AR. BAV patients with AR and root dilatation of 40–50 mm (root phenotype) are associated with significant risk (34%) of post-AVR aortic events. Therefore, simultaneous aortic root surgery is suggested in the patients with BAV-AR and aortic root diameter > 40 mm during their initial AVR procedure [86]. Some of the surgeons recommend aortic repair at the time of BAV surgery if either the aortic diameter exceeds approximately 45 mm or the aortic cross-sectional area/height is above 8–9 cm<sup>2</sup> /m or z score is above 7 [82].

**References**

[1] Basso C, Boschello M, Perrone C, Mecereno A, Cera A, Bicego D, Thiene D, D Dominics E. An echocardiographic survey of primary school children for bicuspid aortic valve.

Bicuspid Aortic Valve

113

http://dx.doi.org/10.5772/intechopen.76643

[2] Fedak PW, Verma S, David TE, Leask RL, Weisel RD, Butany J. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation. 2002;**106**(8):900-904

[3] Klásková E, Zapletalová J, Kaprálová S, Šnajderová M, Lebl J, Tüdös Z, Pavlíček J, Černá J, Mihál V, Stará V, Procházka M. Increased prevalence of bicuspid aortic valve in turner syndrome links with karyotype:The crucial importance of detailed cardiovascular screening. Journal of Pediatric Endocrinology and Metabolism. 2017;**30**(3):319-325

[4] Prakash SK, Bossé Y, Muehlschlegel JD, Michelena HI, Limongelli G, Della Corte A, Pluchinotta FR, Russo MG, Evangelista A, Benson DW, Body SC, Milewicz DM. A roadmap to investigate the genetic basis of bicuspid aortic valve and its complications: Insights from the international BAVCon (bicuspid aortic valve consortium). The Journal

[5] Huntington K, Hunter AG, Chan KL. A prospective study to assess the frequency of familial clustering of congenital bicuspid aortic valve. The Journal of the American

[6] Robledo-Carmona J, Rodríguez-Bailón I, Carrasco-Chinchilla F, Fernández B, Jiménez-Navarro M, Porras-Martin C, Montiel-Trujillo A, García-Pinilla JM, Such-Martínez M, De Teresa-Galván E. Hereditary patterns of bicuspid aortic valve in a hundred families.

[7] Cripe L, Andelfinger G, Martin LJ, Shooner K, Benson DW. Bicuspid aortic valve is heritable. The Journal of the American College of Cardiology. 2004;**44**(1):138-143

[8] Laforest B, Nemer M. GATA5 interacts with GATA4 and GATA6 in outflow tract devel-

[9] Martin LJ, Ramachandran V, Cripe LH, Hinton RB, Aldenfinger G, Tabangin M, Shooner K, Keddache M, Benson DW. Evidence in favor of linkage to human chromosomal regions 18q, 5q and 13q for bicuspid aortic valve and associated cardiovascular malformations.

[10] Goh D, Han L, Judge D. Linkage of familial bicuspid aortic valve with aortic aneurysm

[11] Choudhury N, Bouchot O, Rouleau L, Tremblay D, Cartier R, Butany J, Mongrain R, Leask RL. Local mechanical and structural properties of healthy and diseased human

[12] Yassine NM, Shahram JT, Body SC. Pathogenic mechanisms of bicuspid aortic valve aor-

to chromosome 15q. The American Journal of Human Genetics. 2002;**71**:211

topathy. Frontiers in Physiology. 2017;**8**:687. DOI: 10.3389/fphys.2017.0068

ascending aorta issue. Cardiovascular Pathology. 2009;**18**(2):83-91

The American Journal of Cardiology. 2004;**93**:661-663

of the American College of Cardiology. 2014;**64**(8):832-839

The International Journal of Cardiology. 2013;**168**(4):3443-3449

opment. Developmental Biology. 2011;**358**:368-378

Human Genetics. 2007;**121**:275-284

College of Cardiology. 1997;**30**(7):1809-1812

## **8. Conclusion**

BAV is a very common, congenital, phenotypically variable, and genetically heterogeneous heart disease. It has a complex developmental process and distinct morphological phenotypes. The clinical course is highly non-predictable. Children with BAV are mostly asymptomatic. However, the cases with severe AS may be encountered early in life and need intervention. Aortic dilatation and valvular dysfunction may begin in infancy and make progress with age. The factors determining the prognosis of BAV disease are older age, RN or RL BAV phenotype, flow dynamics (right-handed flow), male gender, elevated systolic blood pressure, smoking, presence of valvular and ventricular dysfunctions, aortic dilatation, endocarditis, high total cholesterol levels, valve degeneration score, and genetic predisposition. Surgery is recommended for the patients with severe valvular dysfunction (AS, AR), aortic dilatation, or aneurysm.

## **Author details**

Ayşe Inci Yıldırım\* and Aysu Türkmen Karaağaç

\*Address all correspondence to: ayildirimmd@yahoo.com

University of Healthy Sciences Kartal Koşuyolu Heart and Research Hospital, Istanbul, Turkey
