**7. Complications associated with BAV**

#### **7.1. Aortic stenosis**

**6.3. Cardiac magnetic resolution imaging**

test [62].

312 Calcific Aortic Valve Disease

or MRI [67].

severe calcified bicuspid aortic valve.

CMRI as a noninvasive diagnostic tool appears to have a high diagnostic sensitivity and specificity. CMRI showed a sensitivity of 100% and a specificity of 95% with steady state freeprecession (SSFP) cine [61]. It seems that CMRI is more reliable than the standard TTE in diagnosing BAV [Figure 5]. When TTE is found to be non-diagnostic for aortic valve mor‐ phology, particularly in patients with severe AS, CMRI can be conducted as a complementary

When the diagnostic results of AR with the use of echocardiography is indefinite or at borderline, CMRI can be used to quantify the AR more accurately [39]. In addition, the valve can be visualized with any correlated lesion of the ascending aorta. This could be used for proper evaluation of the entire aortic and to prepare complex surgical interventions for both the aorta valve and the surrounding cardiovascular structures including the ascending aorta and the aortic root. Of importance, all patients with evidence of BAV should have the aortic root and ascending aorta inspected for indication of aortic dilatation with echocardiography

**Figure 4.** (A) Transthoracic echocardiography short axis view illustrating a normal tricuspid aortic valve. (B) Trans‐ thoracic echocardiography short axis view illustrating a bicuspid aortic valve with fusion of the left and right coronary cusps. (C) Transthoracic echocardiography long axis view illustrating a dilated ascending aorta (Arrow). (D) Transthora‐ cic echocardiography short axis view illustrating a bicuspid aortic valve with fusion of the right and non coronary coro‐ nary cusps. (E) Transthoracic echocardiography short axis view illustrating a severe calcified bicuspid aortic valve with fusion of the right and non coronary coronary cusps. (F) Transthoracic echocardiography long axis view illustrating a

Up to 50% of the adults who present with AS show evidence of BAV disease [71]. BAV degeneration is due to both fibrosis and calcification and is age related [16, 72, 73]. Addition‐ ally, the incidence of BAV related AS that is observed in patients with the age of under 60 years, 60 to 75 years, and more than 75 years are 59%, 40% and 32%, respectively [74].

Patients with BAV generally require AVR 5 years earlier compared with the patients who have an AS of the tricuspid valve [75]. Three-quarters of the patient with BAV who underwent AVR showed to have an isolated AS [7]. Both fibrosis and cusp calcifications occur in an accelerated pattern in BAV compared with tricuspid aortic valve [Figure 4, E &F] [76]. Moreover, several valve related factors seem to accelerate the calcification in BAV including larger sized cusp, presence of raphé and the overall BAV anatomy. It seems that sclerosis of the aortic valve starts in the second decade whereas calcification tends to develop around the fourth decade onwards with a 18 mmHg per decade increase of the average aortic valve gradient [75, 12]. Both R-N BAVs and asymmetrical sized cusps seem to contribute to the acceleration of the stenosis due to the progressive calcification and fibrosis with 27 mm Hg per decade [9, 45, 12]. It has to be noted that smoking and a poor lipid panel are both modifiable independent risk factors that could have a great impact on BAV degeneration [77]. In children, BAV with stenosis can sometimes be treated with balloon valvuloplasty whereas in other cases surgical commissur‐ otomy is indicated [75, 78-80]. Severe fibrosis of the cusp tissue and calcified degeneration, which is found in the older population, make surgical repair difficult or impossible in most cases. AVR is therefore the primary surgical treatment of BAV with severe stenosis in adults.

of aortic dissection is increased 9 fold compared with tricuspid valve cases [16]. Additionally, the area of the aortic dilation also varies among BAV patients. Some patients have a dilatation of the proximal ascending aorta dilation, while others have a dilation of the sinuses of Valsalva and yet other patients present with a dilatation of the transverse arch or a combination of these

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Aortic dilatation of the sinuses of Valsalva is often seen in patients with L-R BAV, whereas patients with R-N BAV present with the dilatation of the ascending aorta [10]. Of note, aortic dilatation and thoracic aortic aneurysm formation could also occur in BAV patients or related family members with the absence of significant valve pathology in the form of AS or AR [51, 68].

Infective endocarditis is a condition high risk on mortality and morbidity which effects 10% to 30% of the BAV patients with actual risk assessment of 0.3% to 2% per patient-years in adults. Although these estimations are based on selected cases, the true incidence of BAV related infective endocarditis is most likely lower. [16, 85, 86]. Moreover, one-fourth of the infective endocarditis cases are a complication due to BAV. Infective endocarditis is frequently seen in young adults and adolescents rather than in elderly patients, particularly the male gender [16]. Almost three-quarters of the endocarditis related BAV cases are caused by *Viridans streptococ‐ ci* and *Staphylococci* [87]. Poor dental hygiene, presence of a dialysis shunt and venous catheters are major independent risk factors for developing infective endocarditis due to the high risk of contamination [88]. Several complications due to infective endocarditis in BAV patient can occur including heart failure, the formation of myocardial or valvular abscess, and mortality within 6 month after hospital admission [89]. Antibiotic prophylaxis is nowadays no longer recommended for patients with BAV and with calcified aortic stenosis, except in BAV patients with a prior history of infective endocarditis, prosthetic heart valves, or prosthetic material

Surgical intervention is the key treatment option for patients with symptomatic BAV disease and the related aortic dilatation. Several factors are dependent on the surgical treatment management including the location and the severity of the aortic dilatation and the perform‐

Surgical intervention for patients with BAV disease occurs at a relative earlier age than for degenerative tricuspid aortic valve disease [71]. In a study of 212 asymptomatic community residents, an average age for surgical intervention was reported for BAV disease versus degenerative tricuspid valve disease of 40± 20 years and 67 ± 16 years, respectively [85]. In Scheme 1, indications for surgical intervention in patients with BAV disease including AR, AS and/or proximal ascending aorta dilation are described. In adults with BAV disease, surgical

**8.1. Surgical indications for aortic valve repair/replacement**

locations [103].

**7.4. Infective endocarditis**

used for heart valve repair [90].

**8. Interventions**

ance status of BAV.

#### **7.2. Aortic regurgitation**

AR most often involves patients with a young age and is less frequently seen than AS with prevalence ranging from 7% to 20% [15, 78, 81, 82]. AR can occur in the isolated form due to the prolapse of one of the cusps, but it could also occur due to and in combination with endocarditis, COA, and proximal aortic root dilatation [16, 25]. The presence of AR could have severe consequences for the patient's morbidity including the increased risk of heart failure, endocarditis and arrhythmia [80]. Aortic root dilatation is found in nearly half of the young adults with BAV disease, thus increasing the risk for AR [83]. In selected cases, patients with BAV disease and isolated AR can be a candidate for aortic valve repair [84].

#### **7.3. Aortic dilatation and dissection**

BAV disease is linked with dilatation of the proximal aortic root and ascending aorta and develops independently from stenotic or regurgitant aortic valvular lesions [91]. This process eventually leads to dissection or rupture of the aortic wall with potentially fatal consequences. Several molecular pathways have been discovered, possibly of genetic basis, which suggest that histopathologic modifications in the extracellular matrix of the dilated proximal aortic wall are a key pathogenesis of aortic dilatation in BAV patients. This includes the loss of smooth muscle cells, cystic medial necrosis and elastic fibre fragmentation [92, 93]. Furthermore, morphometric analysis of the aortic media showed deformities of the elastic lamellae and less elastic tissue in BAV patients in comparison with patients with tricuspid aortic valves [93, 94]. It appears that apoptosis is a key mechanism for the loss of the smooth muscle cells in the ascending aorta of BAV patients which can eventually lead to cardiovascular complications [95, 96, 97]. In addition, regarding the remodeling of the extracellular matrix, fibrillin-1 microfibrils were significantly reduced while the matrix metalloproteinase-2 and -9 activities were significantly increased in the aortic media of BAV patients. When fibrillin-1 deficiency is present, the release of enzymes, also known as matrix metalloproteinases, will increase and weaken the aortic wall by degrading elastic matrix components, thus resulting in aortic dilatation and degeneration [98, 99, 100].

Approximately 40% of the BAV cases develop proximal aortic root dilatation while an estimation of 6% lifetime risk is observed for aortic dissection [101].

Risk factors for developing an adverse aortic complications such as rupture or dissection in BAV patients include positive family history of aortic aneurism, dilatation of the sinotubular junction, the presence of AR, young age (<40 years), and aortic dilatation greater than 50 mm [101, 102]. Aortic dissection occurs most commonly in young adults with an asymptomatic medical history of BAV. A severe risk for aortic dissection is present when the aortic diameter surpasses 50 mm. [102]. When BAV is present in combination with aortic dilatation, the risk of aortic dissection is increased 9 fold compared with tricuspid valve cases [16]. Additionally, the area of the aortic dilation also varies among BAV patients. Some patients have a dilatation of the proximal ascending aorta dilation, while others have a dilation of the sinuses of Valsalva and yet other patients present with a dilatation of the transverse arch or a combination of these locations [103].

Aortic dilatation of the sinuses of Valsalva is often seen in patients with L-R BAV, whereas patients with R-N BAV present with the dilatation of the ascending aorta [10]. Of note, aortic dilatation and thoracic aortic aneurysm formation could also occur in BAV patients or related family members with the absence of significant valve pathology in the form of AS or AR [51, 68].

#### **7.4. Infective endocarditis**

sometimes be treated with balloon valvuloplasty whereas in other cases surgical commissur‐ otomy is indicated [75, 78-80]. Severe fibrosis of the cusp tissue and calcified degeneration, which is found in the older population, make surgical repair difficult or impossible in most cases. AVR is therefore the primary surgical treatment of BAV with severe stenosis in adults.

AR most often involves patients with a young age and is less frequently seen than AS with prevalence ranging from 7% to 20% [15, 78, 81, 82]. AR can occur in the isolated form due to the prolapse of one of the cusps, but it could also occur due to and in combination with endocarditis, COA, and proximal aortic root dilatation [16, 25]. The presence of AR could have severe consequences for the patient's morbidity including the increased risk of heart failure, endocarditis and arrhythmia [80]. Aortic root dilatation is found in nearly half of the young adults with BAV disease, thus increasing the risk for AR [83]. In selected cases, patients with

BAV disease is linked with dilatation of the proximal aortic root and ascending aorta and develops independently from stenotic or regurgitant aortic valvular lesions [91]. This process eventually leads to dissection or rupture of the aortic wall with potentially fatal consequences. Several molecular pathways have been discovered, possibly of genetic basis, which suggest that histopathologic modifications in the extracellular matrix of the dilated proximal aortic wall are a key pathogenesis of aortic dilatation in BAV patients. This includes the loss of smooth muscle cells, cystic medial necrosis and elastic fibre fragmentation [92, 93]. Furthermore, morphometric analysis of the aortic media showed deformities of the elastic lamellae and less elastic tissue in BAV patients in comparison with patients with tricuspid aortic valves [93, 94]. It appears that apoptosis is a key mechanism for the loss of the smooth muscle cells in the ascending aorta of BAV patients which can eventually lead to cardiovascular complications [95, 96, 97]. In addition, regarding the remodeling of the extracellular matrix, fibrillin-1 microfibrils were significantly reduced while the matrix metalloproteinase-2 and -9 activities were significantly increased in the aortic media of BAV patients. When fibrillin-1 deficiency is present, the release of enzymes, also known as matrix metalloproteinases, will increase and weaken the aortic wall by degrading elastic matrix components, thus resulting in aortic

Approximately 40% of the BAV cases develop proximal aortic root dilatation while an

Risk factors for developing an adverse aortic complications such as rupture or dissection in BAV patients include positive family history of aortic aneurism, dilatation of the sinotubular junction, the presence of AR, young age (<40 years), and aortic dilatation greater than 50 mm [101, 102]. Aortic dissection occurs most commonly in young adults with an asymptomatic medical history of BAV. A severe risk for aortic dissection is present when the aortic diameter surpasses 50 mm. [102]. When BAV is present in combination with aortic dilatation, the risk

estimation of 6% lifetime risk is observed for aortic dissection [101].

BAV disease and isolated AR can be a candidate for aortic valve repair [84].

**7.2. Aortic regurgitation**

314 Calcific Aortic Valve Disease

**7.3. Aortic dilatation and dissection**

dilatation and degeneration [98, 99, 100].

Infective endocarditis is a condition high risk on mortality and morbidity which effects 10% to 30% of the BAV patients with actual risk assessment of 0.3% to 2% per patient-years in adults. Although these estimations are based on selected cases, the true incidence of BAV related infective endocarditis is most likely lower. [16, 85, 86]. Moreover, one-fourth of the infective endocarditis cases are a complication due to BAV. Infective endocarditis is frequently seen in young adults and adolescents rather than in elderly patients, particularly the male gender [16]. Almost three-quarters of the endocarditis related BAV cases are caused by *Viridans streptococ‐ ci* and *Staphylococci* [87]. Poor dental hygiene, presence of a dialysis shunt and venous catheters are major independent risk factors for developing infective endocarditis due to the high risk of contamination [88]. Several complications due to infective endocarditis in BAV patient can occur including heart failure, the formation of myocardial or valvular abscess, and mortality within 6 month after hospital admission [89]. Antibiotic prophylaxis is nowadays no longer recommended for patients with BAV and with calcified aortic stenosis, except in BAV patients with a prior history of infective endocarditis, prosthetic heart valves, or prosthetic material used for heart valve repair [90].

## **8. Interventions**

Surgical intervention is the key treatment option for patients with symptomatic BAV disease and the related aortic dilatation. Several factors are dependent on the surgical treatment management including the location and the severity of the aortic dilatation and the perform‐ ance status of BAV.

#### **8.1. Surgical indications for aortic valve repair/replacement**

Surgical intervention for patients with BAV disease occurs at a relative earlier age than for degenerative tricuspid aortic valve disease [71]. In a study of 212 asymptomatic community residents, an average age for surgical intervention was reported for BAV disease versus degenerative tricuspid valve disease of 40± 20 years and 67 ± 16 years, respectively [85]. In Scheme 1, indications for surgical intervention in patients with BAV disease including AR, AS and/or proximal ascending aorta dilation are described. In adults with BAV disease, surgical intervention in the form of AVR is recommended when severe AS, chronic AR and left ventricle dysfunction (LV) with a LV ejection fraction (EF) of < 50% is present. Furthermore, adolescents and young adults with severe AR who have developing symptoms, persistent LV dysfunction with LV EF < 50%, or progressive LV dilatation, are also suitable candidates for AVR [39]. Several factors has to be kept in mind when choosing a patient tailored intervention namely, the risk for reoperation with bioprosthetic valves due to valve degeneration, and the necessity of lifelong anticoagulation with mechanical valve replacement. In athletic patients, bleeding risks due to chronic use of anticoagulation should be discussed, as well as the potential risk of teratogenic dangers of warfarine for women who desire pregnancy in the future. The discus‐ sion of the risk and benefits for both procedures is therefore mandatory.

evaluation of the aortic root and ascending aorta is therefore mandatory in patients with BAV with echocardiography or MRI to determine the potential presence of an aortic dilatation [67].

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Systematic high blood pressure is an independent risk factor for developing complications including aorta dissection in patients with stenotic BAV with aortic root dilatation. Β-blocker therapy is therefore advisable for patients with BAV disease [39]. Moreover, osteogenic and proteolytic activities,which is a precursor to atherosclerotic and calcified degenerative AS, have been revealed in early aortic valve disease with the use of multimodality molecular imaging [115]. However, lipid lowering therapy didn't reduce calcific valve progression with respect to moderate to severe AS [116, 134]. Although, little evidence have acknowledged the beneficial use of statins in BAV disease, patients with BAV disease who have risk factors for atherosclerosis should receive statins with the purpose of reducing the degenerative risk in the aorta and potentially preventing atherosclerosis. Long-term vasodilator therapy is only recommended in BAV patients with AR if systematic hypertension is present [39]. Despite this, there is currently no concrete evidence suggesting that pharmacological treatments could alter

**Scheme 2.** Cardiac surgical options for aortic dilatation in patients with bicuspid aortic valve disease. AR = aortic re‐

The surgical options are illustrated in Scheme 2 for BAV disease with aortic dilatation. When patients require an intervention of the aortic valve with an aortic diameter < 45 mm, the main surgical option is a bioprosthetic AVR, mechanical AVR, the Ross procedure which is contra‐ indicated in older patients with BAV and onset of aortic dilatation, or aortic valve repair in selected cases of AR. In patients with > 45 mm ascending aorta root dilatation with significant

**8.3. Pharmacological treatment options**

gurgitation, AS = Aortic stenosis.

**8.4. Surgical options**

the natural history or halt the development BAV calcifiation.

**Scheme 1.** Indication for cardiac surgical intervention in patients with bicuspid aortic valve disease including aortic regurgitation (AR), aortic stenosis (AS), and/or aortic dilatation. LVEF = left ventricle ejection fraction; LV dilatation = Left ventricle dilatation (End-systolic diameter > 55mm or end-diastolic diameter > 75 mm); Clinical symptoms include dyspnoea, angina, or syncope; Severe AS = jet velocity > 4 m/s, mean gradient. 40 mm Hg, valve area < 1 cm²; severe AR = jet width < 65% of LOVT, vena contracta width > 0.6 cm, regurgitant volume > 60 mL, regurgitant fraction > 60%, regurgitant orifice area >0.3 cm². AVR = aortic valve replacement (Data derived from Bonow *et al.* [39]).

#### **8.2. Surgical indications for ascending aorta dilation**

As mentioned earlier, BAV disease is associated with aortic dilatation. BAV patients with the presence of AR or AS should receive surgical intervention of the ascending aorta when an aortic diameter of ≥ 45 mm is present. Conversely, BAV patients with absence of additional risk factors and co morbidities should receive surgical intervention at an aortic root or ascending aorta dilatation of ≥ 50 mm or a aortic dilatation expansion rate of ≥ 5 mm per year [39]. However, it seems that aortic size relative to body size could be a more superior novel technique to define high risk patients requiring surgical intervention [104]. Proper routine evaluation of the aortic root and ascending aorta is therefore mandatory in patients with BAV with echocardiography or MRI to determine the potential presence of an aortic dilatation [67].

#### **8.3. Pharmacological treatment options**

intervention in the form of AVR is recommended when severe AS, chronic AR and left ventricle dysfunction (LV) with a LV ejection fraction (EF) of < 50% is present. Furthermore, adolescents and young adults with severe AR who have developing symptoms, persistent LV dysfunction with LV EF < 50%, or progressive LV dilatation, are also suitable candidates for AVR [39]. Several factors has to be kept in mind when choosing a patient tailored intervention namely, the risk for reoperation with bioprosthetic valves due to valve degeneration, and the necessity of lifelong anticoagulation with mechanical valve replacement. In athletic patients, bleeding risks due to chronic use of anticoagulation should be discussed, as well as the potential risk of teratogenic dangers of warfarine for women who desire pregnancy in the future. The discus‐

**Scheme 1.** Indication for cardiac surgical intervention in patients with bicuspid aortic valve disease including aortic regurgitation (AR), aortic stenosis (AS), and/or aortic dilatation. LVEF = left ventricle ejection fraction; LV dilatation = Left ventricle dilatation (End-systolic diameter > 55mm or end-diastolic diameter > 75 mm); Clinical symptoms include dyspnoea, angina, or syncope; Severe AS = jet velocity > 4 m/s, mean gradient. 40 mm Hg, valve area < 1 cm²; severe AR = jet width < 65% of LOVT, vena contracta width > 0.6 cm, regurgitant volume > 60 mL, regurgitant fraction > 60%, regurgitant orifice area >0.3 cm². AVR = aortic valve replacement (Data derived from Bonow *et al.* [39]).

As mentioned earlier, BAV disease is associated with aortic dilatation. BAV patients with the presence of AR or AS should receive surgical intervention of the ascending aorta when an aortic diameter of ≥ 45 mm is present. Conversely, BAV patients with absence of additional risk factors and co morbidities should receive surgical intervention at an aortic root or ascending aorta dilatation of ≥ 50 mm or a aortic dilatation expansion rate of ≥ 5 mm per year [39]. However, it seems that aortic size relative to body size could be a more superior novel technique to define high risk patients requiring surgical intervention [104]. Proper routine

**8.2. Surgical indications for ascending aorta dilation**

sion of the risk and benefits for both procedures is therefore mandatory.

316 Calcific Aortic Valve Disease

Systematic high blood pressure is an independent risk factor for developing complications including aorta dissection in patients with stenotic BAV with aortic root dilatation. Β-blocker therapy is therefore advisable for patients with BAV disease [39]. Moreover, osteogenic and proteolytic activities,which is a precursor to atherosclerotic and calcified degenerative AS, have been revealed in early aortic valve disease with the use of multimodality molecular imaging [115]. However, lipid lowering therapy didn't reduce calcific valve progression with respect to moderate to severe AS [116, 134]. Although, little evidence have acknowledged the beneficial use of statins in BAV disease, patients with BAV disease who have risk factors for atherosclerosis should receive statins with the purpose of reducing the degenerative risk in the aorta and potentially preventing atherosclerosis. Long-term vasodilator therapy is only recommended in BAV patients with AR if systematic hypertension is present [39]. Despite this, there is currently no concrete evidence suggesting that pharmacological treatments could alter the natural history or halt the development BAV calcifiation.

**Scheme 2.** Cardiac surgical options for aortic dilatation in patients with bicuspid aortic valve disease. AR = aortic re‐ gurgitation, AS = Aortic stenosis.

#### **8.4. Surgical options**

The surgical options are illustrated in Scheme 2 for BAV disease with aortic dilatation. When patients require an intervention of the aortic valve with an aortic diameter < 45 mm, the main surgical option is a bioprosthetic AVR, mechanical AVR, the Ross procedure which is contra‐ indicated in older patients with BAV and onset of aortic dilatation, or aortic valve repair in selected cases of AR. In patients with > 45 mm ascending aorta root dilatation with significant aortic valve pathology, aortic root replacement therapy, (Bentall procedure) is the main surgical option.

patients with severe BAV pathology with normal-sized sinuses and dilatation of the supra‐

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Valve sparing aortic root replacement procedure may be an alternative to Bentall procedures in selected BAV patients such as young adults who present with aortic root lesion with normally functioning aortic valve including the absence of calcified aortic valves, multileaflet prolapsed and annular dilatation [112]. Two variations for this procedure have been described namely the remodeling (Yacoub) procedure and the re-implantation (David) procedure [113, 114]. The coronary artery ostia are removed as buttons in both procedures followed by reimplantation of a Dacron aortic graft with additional leaflet repair, if required. However, in the David procedure, the aortic root is mobilized to below the plane of the ventriculo-aortic junction followed by a Dacron graft replacement which is telescoped down outside the aortic root to provide a functional aortic annuloplasty. It seems that there is no significant difference between these two procedures in BAV patients. Valve sparing procedures are more surgically changeling than the traditional Bentall procedure and are only conducted in specialized aortic centres. When tubular ascending aorta dilatation is present with no root or valve pathology, supracoronary ascending aortic replacement is required in BAV patients. When valve pathol‐ ogy is present with this anatomical lesion, a Wheat procedure should be preformed. This procedure includes separate AVR or repair leaving the sinus segment intact. However, due to the fact that in most cases sclerosis of the aortic valve starts in the second decade and calcifi‐ cation begins to develop around the fourth decade, serious consideration have to be made with respect to valve-sparing replacement of a dilated aorta in young adults with normally

Due to the growth of adolescents during childhood, prosthetic valve insertion is unsatisfactory. Balloon valvuloplasty is therefore a successful treatment option because of the fact the aortic valve is not calcified at this age of the child and the fact that valvuloplasty disrupts the commissural fusion and reduces the obstruction when implemented. Balloon valvuloplasty is indicated in young adults and adolescents without significantly calcified BAV and no AR who experience symptoms with a peak-to-peak gradients of > 50 mm Hg. Also, asymptomatic adolescents who develop ST- or T wave changes with exercise or rest or demonstrate a peakto-peak gradient of > 60 mm Hg should be considered candidates for balloon valvuloplasty. Additional indications for balloon valvuloplasty are asymptomatic adolescent or young adult who are interested in sport activities or becoming pregnant with a peak-to-peak gradient > 50 mm Hg. When severe AR is evident after balloon valvulplasty, AVR should be considered. Conversely, valvuloplasty is seldom performed in old adults due to often severe calcification of the aortic valve [39, 86]. However, balloon valvuloplasty should be considered as a bridge to surgery in adults with AS who have a high risk for AVR, who are hemodynamically unstable, or when AVR is not possible to perform due to secondary co morbidities. Excellent mid-term results have been observed after balloon valvuloplasty at experienced centres [117-119].

coronary ascending aorta.

functioning BAV [12, 75].

**8.9. Balloon valvuloplasty**

**8.8. Yacoub and David procedure**

#### **8.5. Valve repair**

Surgical repair can be considered when BAV disease is presented without any significant signs of calcification or valve thickening [105]. Several surgical repair options are available including raphé resection with or without leaflet placation, shortening or reinforcement of the free margin, augmentation of the pericardial patch cusp, aortic root repair, and subcommissural annuloplasty [105, 106]. Patients with BAV disease show evidence of sclerosis after the second decade and calcification associated with increasing stenosis at the fourth decade [12, 75]. This raises the question with respect to valve sparing replacement of a dilated aorta, especially in young patients. Although, it appears that the need for reoperation is greater in the surgical repair group for AR, this surgical option still remains attractive in both young adults with AR and women with BAV disease who want to become pregnant.

#### **8.6. Ross procedure**

The Ross procedure, also known as the pulmonary autograft, is a cardiac surgical procedure in which the pathological aortic valve is replaced with a patient's own pulmonary valve after which a pulmonary allograft is performed with a valve from a donor which is then used to substitute the patient's own pulmonary valve. Several benefits have been reported with the Ross procedure including the absence of anticoagulation, reduced endocarditis risk, and encouraging valve hemodynamic gradients [107]. However, major concerns have been raised including the most important concern regarding the durability of the autograft and allograft. In addition, another key concern is that histopathologic alterations of the pulmonary trunk may occur, after which the pulmonary trunk can show resemblances of the proximal aorta, thus increasing the risk for aortic aneurysms with a reoperation being the most likely end result [108]. The Ross procedure has no beneficial benefits over conventional AVR in adult patients with respect to hemodynamics or postoperative outcomes. Nevertheless, the Ross procedure offers adolescents, young adults and women with BAV disease who want to become pregnant, an adequate solution in the first decade after the operation. However, limitation with respect to the durability is evident by the end of the first postoperative decade, especially in younger patients [109]. Ross procedure in the setting of BAV disease still remains controversial and should only be performed in selected cases in specialized centres.

#### **8.7. Bentall procedure**

Due to the risk of aortic dilatation in patients with BAV disease, the majority of the surgeons evaluate the option of reinforcing or replace the ascending aorta with at the time of the valve surgery. The Bentall procedure is a widely used surgical procedure for patients with BAV and aortic root dilatation. This procedure includes the replacement of the aortic valve, aortic root and ascending aorta with the reimplantation of the coronary arteries [110]. Excellent long-term results have been observed with the Bentall procedure with respect to survival in patients with aortic valve disease and aorta dilatation [111]. This procedure is a suitable intervention in older patients with severe BAV pathology with normal-sized sinuses and dilatation of the supra‐ coronary ascending aorta.

#### **8.8. Yacoub and David procedure**

aortic valve pathology, aortic root replacement therapy, (Bentall procedure) is the main

Surgical repair can be considered when BAV disease is presented without any significant signs of calcification or valve thickening [105]. Several surgical repair options are available including raphé resection with or without leaflet placation, shortening or reinforcement of the free margin, augmentation of the pericardial patch cusp, aortic root repair, and subcommissural annuloplasty [105, 106]. Patients with BAV disease show evidence of sclerosis after the second decade and calcification associated with increasing stenosis at the fourth decade [12, 75]. This raises the question with respect to valve sparing replacement of a dilated aorta, especially in young patients. Although, it appears that the need for reoperation is greater in the surgical repair group for AR, this surgical option still remains attractive in both young adults with AR

The Ross procedure, also known as the pulmonary autograft, is a cardiac surgical procedure in which the pathological aortic valve is replaced with a patient's own pulmonary valve after which a pulmonary allograft is performed with a valve from a donor which is then used to substitute the patient's own pulmonary valve. Several benefits have been reported with the Ross procedure including the absence of anticoagulation, reduced endocarditis risk, and encouraging valve hemodynamic gradients [107]. However, major concerns have been raised including the most important concern regarding the durability of the autograft and allograft. In addition, another key concern is that histopathologic alterations of the pulmonary trunk may occur, after which the pulmonary trunk can show resemblances of the proximal aorta, thus increasing the risk for aortic aneurysms with a reoperation being the most likely end result [108]. The Ross procedure has no beneficial benefits over conventional AVR in adult patients with respect to hemodynamics or postoperative outcomes. Nevertheless, the Ross procedure offers adolescents, young adults and women with BAV disease who want to become pregnant, an adequate solution in the first decade after the operation. However, limitation with respect to the durability is evident by the end of the first postoperative decade, especially in younger patients [109]. Ross procedure in the setting of BAV disease still remains controversial and

Due to the risk of aortic dilatation in patients with BAV disease, the majority of the surgeons evaluate the option of reinforcing or replace the ascending aorta with at the time of the valve surgery. The Bentall procedure is a widely used surgical procedure for patients with BAV and aortic root dilatation. This procedure includes the replacement of the aortic valve, aortic root and ascending aorta with the reimplantation of the coronary arteries [110]. Excellent long-term results have been observed with the Bentall procedure with respect to survival in patients with aortic valve disease and aorta dilatation [111]. This procedure is a suitable intervention in older

and women with BAV disease who want to become pregnant.

should only be performed in selected cases in specialized centres.

surgical option.

318 Calcific Aortic Valve Disease

**8.5. Valve repair**

**8.6. Ross procedure**

**8.7. Bentall procedure**

Valve sparing aortic root replacement procedure may be an alternative to Bentall procedures in selected BAV patients such as young adults who present with aortic root lesion with normally functioning aortic valve including the absence of calcified aortic valves, multileaflet prolapsed and annular dilatation [112]. Two variations for this procedure have been described namely the remodeling (Yacoub) procedure and the re-implantation (David) procedure [113, 114]. The coronary artery ostia are removed as buttons in both procedures followed by reimplantation of a Dacron aortic graft with additional leaflet repair, if required. However, in the David procedure, the aortic root is mobilized to below the plane of the ventriculo-aortic junction followed by a Dacron graft replacement which is telescoped down outside the aortic root to provide a functional aortic annuloplasty. It seems that there is no significant difference between these two procedures in BAV patients. Valve sparing procedures are more surgically changeling than the traditional Bentall procedure and are only conducted in specialized aortic centres. When tubular ascending aorta dilatation is present with no root or valve pathology, supracoronary ascending aortic replacement is required in BAV patients. When valve pathol‐ ogy is present with this anatomical lesion, a Wheat procedure should be preformed. This procedure includes separate AVR or repair leaving the sinus segment intact. However, due to the fact that in most cases sclerosis of the aortic valve starts in the second decade and calcifi‐ cation begins to develop around the fourth decade, serious consideration have to be made with respect to valve-sparing replacement of a dilated aorta in young adults with normally functioning BAV [12, 75].

#### **8.9. Balloon valvuloplasty**

Due to the growth of adolescents during childhood, prosthetic valve insertion is unsatisfactory. Balloon valvuloplasty is therefore a successful treatment option because of the fact the aortic valve is not calcified at this age of the child and the fact that valvuloplasty disrupts the commissural fusion and reduces the obstruction when implemented. Balloon valvuloplasty is indicated in young adults and adolescents without significantly calcified BAV and no AR who experience symptoms with a peak-to-peak gradients of > 50 mm Hg. Also, asymptomatic adolescents who develop ST- or T wave changes with exercise or rest or demonstrate a peakto-peak gradient of > 60 mm Hg should be considered candidates for balloon valvuloplasty. Additional indications for balloon valvuloplasty are asymptomatic adolescent or young adult who are interested in sport activities or becoming pregnant with a peak-to-peak gradient > 50 mm Hg. When severe AR is evident after balloon valvulplasty, AVR should be considered. Conversely, valvuloplasty is seldom performed in old adults due to often severe calcification of the aortic valve [39, 86]. However, balloon valvuloplasty should be considered as a bridge to surgery in adults with AS who have a high risk for AVR, who are hemodynamically unstable, or when AVR is not possible to perform due to secondary co morbidities. Excellent mid-term results have been observed after balloon valvuloplasty at experienced centres [117-119].

#### **8.10. Transcatheter aortic valve implantation**

Transcatheter aortic valve implantation (TAVI) is a novel minimally invasive technique indicated for patients who are contraindicated for cardiac surgery due to associated comor‐ bilities or who have a high risk of perioperative mortality. TAVI is an alternative treatment for patients with valve disease in which a valve replacement is introduced through the femoral artery via a small incision or in some cases, an incision into the chest after which the catheter is inserted into the left ventricular apex, also known as the transapical approach. Other methods include subclavian in which the catheter is inserted beneath the collar bone and direct aortic incision in which the catheter is inserted directly into the aorta via a minimally invasive incision in the chest [120]. Due to the asymmetric anatomy which is observed with BAV disease, the TAVI device could potentially be affected to a noncircular expansion, thus creating an elevated risk of paravalvular leak [121]. Due to this major concern, BAV is considered a contraindication with respect to TAVI. BAV have been overall excluded in all the major TAVI trials in which little clinical experience is now known with regard to TAVI in BAV cases. However, several centres showed acceptable results in selected BAV patients with AS [121-123]. A high risk of suboptimal device seating has been observed in BAV patients with asymmetric valvular anatomy, AR, and bulky leaflets. Whether novel valve designs could improve TAVI performance in the BAV group, still remains uncertain.

**10. Sport participation**

surgery [124].

**11. Pregnancy**

mortality rates still remains rare [126, 127].

to strategy and recommendations for sport activity.

The vast majority of young adults with BAV disease are asymptomatic. Little is known regarding the risks of aortic dissection and sudden cardiac death in young adults with BAV who participate in athletic activity. Also, the severity of the valve pathology and aortic root dilatation in this subgroup of BAV patients influence the clinical decision making with respect

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No restrictions are necessary with respect to BAV patients with an athletic lifestyle who present with a mild AS. However, asymptomatic BAV patients with moderate AS can only conduct low-intensity athletic competitive activities. Exercise stress testing is mandatory for BAV patients with moderate AS to detect any additional risk factors including unusual blood pressure during exercise, onset of symptoms during exercise or pathological arrhythmias, which could eventually alter the clinical strategy and recommendations. In addition, BAV patients with symptomatic moderate or severe AS should receive immediate surgical inter‐ vention and should therefore not participate in any form of competitive sport activities upon

BAV patients with mild enlargement of the left ventricular end-diastolic dimension and mild to moderate AR have no restriction in participating in all forms of athletic activity. Also in this case, an exercise stress testing should be performed to estimate the risk. Patients with BAV disease who have a definite LV enlargement of ≥ 60 mm, pulmonary hypertension, or any degree of LV systolic dysfunction at rest should avoid any form of competitive sport activities

Also, BAV patients with severe AR and left ventricular end-diastolic diameter > 65 mm should avoid any form of competitive sport activities. This also includes BAV patients with mild-to moderate AR associated with positive symptoms for valve disease [124]. Young adults with uncalcified AS with a peak-to-peak gradient > 50 mm Hg should who play competitive sports are candidates for aortic balloon valvuloplasty [39]. The recommendation for sport activity for BAV patients with respect to dilatation of the proximal aortic root depends on the level of severity the aortic dilatation. BAV patients with an aortic root diameter of 40 to 45 mm should only perform low to moderate intensity sport activity and preferably avoid any form of contact sport. Moreover, BAV patients with an aortic root diameter of > 45 mm are allowed to conduct low-intensity sport activity due to due to the potential risk of aortic root dissection [125].

Although, the vast majority of pregnancies with congenital AS go through labour uncompli‐ cated, some pregnancies with severe AS have a higher risk rate of morbidity, although the

[124]. BAV patients who underwent an AVR should avoid any form of contact sport.

### **9. Surveillance**

All patients with BAV disease whether AS, AR, operated or not, should receive lifelong serial follow-up depending on symptoms and degree of the functional disorder. Moreover, serial follow-up with imaging assessment with respect to the cardiac and aortic anatomy including valve function, LV function, diameter of both ascending aorta, sinotublular junction, sinuses of Valsvalva and the annulus should be performed in BAV patients regardless the severity of the pathology. TTE is a reliable diagnostic tool to monitor the aortic valve and ascending aorta. However, it should be noted that it is difficult to obtain adequate imaging with the TTE regarding the mid and distal ascending aorta and arch, especially in BAV patients with large body index, in which MRI or CT scan should be used.

The occurrence of imaging should depend on the size of the aortic root at the initial assessment. If the aortic root is < 40 mm with no clinical symptom alternations, the ascending aorta should be reimaged every 2 years. Whereas, if the aortic root is ≥ 40 mm, it is should be reimaged annually or even more often if progression of the aortic root dilatation is present or whenever a change in clinical symptoms and/or findings occur with echocardiography or MRI [39]. Also of importance, first degree family members of patients with BAV disease should receive echocardiographic screening due to the increased risk of cardiovascular abnormalities [39].
