**3. Aortic repair**

Many aortic repair techniques have evolved since their first introduction resulting in improved mortality and reintervention rates. However, its place in the management of patients with aortic valve disease is still controversial. Another big debate is whether aortic repair or replacement is superior, despite most agreeing that aortic valve replacement is inevitable in patients with congenital aortic valve disease.

The aortic repair can range from simple techniques such as commissurotomy to complex ones such as aortic valve neocuspidization. To perform a precise aortic valve repair, it is imperative to understand that the aortic valve operates as a unit consisting of the ventriculo-aortic (VAJ) and sino-tubular junction (STJ). These provide a framework for a functional annulus and cusps (**Figure 1**). Hence, both the annulus and cusps need to be considered at the time of surgery to ensure a proper repair [4, 23–26]. The ideal goal of any aortic valve repair is to restore the leaflets and functional aortic annulus to their normal geometry while ensuring normal mobility of the valve cusps [24].

A repair-oriented functional classification was developed to improve understanding of the pathophysiology and communication between physicians [27, 28]. With this classification, an algorithm can be established to guide physicians to the correct procedure. Type 1 refers to defects in the functional annulus, and it is divided into several subtypes. Type 1a refers to dilation in the STJ and ascending aorta, type 1b indicates dilation is in the STJ, sinuses of Valsalva, and the VAJ, and lastly type 1c refers to pure dilation of the VAJ. Depending on the subgroup, the regurgitant jet differs and physicians will be able to determine the type of annuloplasty that is appropriate [24, 26–30]. Type 2 refers to aortic insufficiency caused by cusp prolapse due to excessive motion of the aortic cusps [24, 26–28]. These are generally managed by resuspension, free margin plication, or triangular resection techniques [27–29]. Lastly, there is type 3 aortic insufficiency where cusp motion is restricted, possibly due to thickening and fibrosis. This is potentially the most challenging pathology for repair procedures as an additional patch augmentation is frequently needed which can result in structural degradation [24, 26–28, 31]. Other aortic valve pathologies that are not classified are cusp perforation and aortic stenosis. Cusp perforations are generally repaired directly with a patch [28]. Materials for leaflet

**Figure 1.** *Anatomy of the aortic valve.*

## *Advances in the Management of Congenital Malformations of the Aortic Valve DOI: http://dx.doi.org/10.5772/intechopen.105641*

and patch repair will be discussed in a later section. Aortic stenosis is commonly managed with commissurotomy [29] or reconstruction, depending on the complexity, if the repair route is chosen.

Since bicuspid aortic valves are the most prevalent aortic valve disease, these are also the most commonly repaired morphology [29]. They often present with defects that are combined from the subgroups listed above, with the most common being prolapse of the fused cusp with dilation in the annulus [24, 28, 32]. Cusp configuration of bicuspid aortic valves uses a different classification first proposed by Sievers and Schmidtkes (**Table 1**). The most common, type 1, refers to a bicuspid valve with a median raphe and asymmetrical aortic sinuses, and type 0 refers to a symmetrical bicuspid valve with no raphe present [24, 27]. Repairs for type 0 valves are usually straightforward and performed in a similar fashion to tricuspid valves, where the nonprolapsed cusp is used as the reference height for plication or resuspension. In type 1 repairs, patch augmentation may be required depending on the amount of native cusp tissue left after shaving or debridement [24]. For patients where annulus dilation is present, a valve-sparing reimplantation technique for annuloplasty might be preferred as it carries less risk for recurrent dilation. Although reimplantation is a more technically challenging procedure, compared to a subcommisural annuloplasty, both techniques are similar in terms of morbidity [24, 33]. Hence, surgeons who have the expertise should consider performing valve-sparing implantation for better long-term outcomes. The overall goal in the repair of bicuspid valves should meet the following two criteria to ensure an optimal aortic root geometry: 1) the basal ring diameter should be reduced to less than 25 mm, 2) effective cusp height should be restored to above 8 mm. This will lead to better long-term valve stability and minimize degradation rate of the tissues [28].

Unicuspid aortic valves were previously classified under the Sievers classification for BAV as Type 2 due to the presence of two raphes; however many now consider it as a separate entity due to its unique anatomy [32, 34]. There are two main types of unicuspid aortic valves – either unicommissural (most common) where an eccentric slit-like orifice is present with one commissural attachment, or a commissural where there is a pinhole orifice with no commissural attachment [34–37]. Management of unicuspid aortic valve remains a challenge since patients often have dysplastic and severely calcified cusps with no functional native tissue [28]. Therefore, the aortic replacement has been the main method of management for a unicuspid aortic valve for many decades; however, more are turning to repair first and delaying replacement to prevent complications from valve replacement [38].


#### **Table 1.**

*Sievers and Schmidtkes classification for bicuspid aortic valve.*

### **3.1 Bicuspidization**

Schäfers et al. proposed the first unicuspid aortic valve bicuspidization repair technique which consisted of a reconstructive approach for unicommissural unicuspid aortic valve with aortic regurgitation or dilatation [34, 36]. The technique utilized stay sutures on the commissure with normal height, as well as one placed at the same height above the rudimentary anterior commissure to indicate the location of the new commissure. The fused cusp tissue was then incised anteriorly. Glutaraldehydetreated autologous pericardium was then used to fill the gap between the rudimentary cusp and new commissure, and also for the defect of the fused cusp so that it is in the position of the rudimentary cusp [36]. This ultimately leads to a standard asymmetric BAV configuration with 2 normal commissures [34]. The key parameter in this repair was an effective cusp height of 8 mm in pediatric and 10 mm in adult repairs to ensure a near-normal geometry to guarantee consistency and reliable results. The technique was performed on 20 patients with a mean age of 26. Schafers et al. reported good initial functional results with satisfactory hemodynamics post repair. At 4 years following repair, freedom from moderate or more aortic regurgitation was 77%, freedom from reoperation was 67%, and freedom from aortic valve replacement was 100%. However, the durability of autologous pericardium for cusp extension was not explored in this study. Furthermore, due to the short follow-up period, cusp configuration as a patient grows is also unknown [36].

Aicher et al. investigated hemodynamic effects and overall stability differences between the asymmetric reconstruction technique proposed by Schafers et al. previously, and a similar symmetric bicuspidization cusp reconstruction. The study consisted of 118 patients at a mean age of 27 years with either aortic stenosis, aortic regurgitation, or both. Glutaraldehyde-treated autologous pericardium was used for both groups, and both the effective and geometric heights were kept consistent at 10 mm and > 20 mm, respectively. Overall, there was no significant difference in reoperation rates between the configurations; however, the symmetric configuration yielded better hemodynamics with lower mean and peak gradients, especially during exercise [39]. Furthermore, Aicher et al. and Franciulli et al. combined the repair technique to include root remodeling to address aneurysm of ascending aorta and aortic roots which occur commonly in the unicuspid aortic valve. Dilation of the VAJ had previously been identified as a risk factor for repair failure [40]. Both studies reported improvement in the durability comparted to isolated aortic valve repair. Additionally, Franciulli et al. reported postoperative hemodynamics similar to age-matched patient population with tricuspid aortic valve.

Kolesar et al. extended the symmetrical cusp repair technique to 17 patients with stenotic unicuspid aortic valve and a mean age of 23 years. They also agreed on the importance of ensuring a standardized cusp effective height to minimize the risk of reoperation. Kolesar and colleagues also performed open extra-aortic ring implantation using a Dacron tubular graft in patients with annulus ≥25 mm, given the high risk of aortic annulus dilatation in unicuspid aortic valve. They reported that performing a ring annuloplasty in valve-sparing aortic valve repair significantly increases freedom from valve-related reoperation and freedom from moderate or worse aortic regurgitation. Freedom from valve-related reoperation was 100%, although the follow-up period was too short (about 2 years). Similar to the previous studies, they also highlighted the importance of creating a symmetrical orientation with the new commissure. One difference between the repair techniques proposed by Kolesar and Schafer is that Kolesar used equine pericardium instead of autologous pericardium.

#### *Advances in the Management of Congenital Malformations of the Aortic Valve DOI: http://dx.doi.org/10.5772/intechopen.105641*

Despite this, Kolesar reported no statistically significant difference in freedom of reoperation between the two patch materials [37].

Matsushima et al. [41] proposed that management of unicuspid aortic valve, whether aortic stenosis or regurgitation, should be a three-stage approach - firstly, balloon aortic valvulotomy during infancy or neonatal period, then bicuspidization with cusp augmentation, and lastly aortic valve replacement mainly with a pulmonary autograft later in life if needed. They also used a symmetrical bicuspidization technique and involved 60 patients who are 18 years old or younger in the study. These authors reported an overall survival of 96% at 5 and 10 years. However, 33% of patients required aortic valve reoperation, mainly due to patch degeneration. The authors also agreed with Kolesar et al. that an external suture annuloplasty is necessary during the repair to improve cusp coaptation, reduce cusp stress and prevent suture dehiscence especially if the aortic root is dilated.

The authors also noted that bicuspidization using their technique can be done even after a balloon aortic valvuloplasty is performed during neonatal period. Their repair technique can tolerate cusp tear which occurs commonly during balloon valvuloplasty. Therefore, initial balloon valvulotomies are not a contraindication for their bicuspidization cusp repair technique. In balloon dilation for unicuspid aortic valve, tears commonly occur opposite to the normal commissure, which in this case is removed for this bicuspidization technique, hence avoiding the controversial debate on initial management plan [41]. They utilized three different patch materials for cusp augmentation – glutaraldehyde-treated autologous pericardium, decellularized xenogenic tissue, and expanded polytetrafluoroethylene (ePTFE) membrane. For each material, freedom from aortic valve reoperation using autologous pericardium was 72% and 52% at 5 and 10 years respectively. 50% of patients with ePTFE membrane required aortic valve reoperation later in life; however, this sample size was small (2 out of 4 patients). None of the patients with decellularized xenogeneic tissue required aortic valve reoperation. They concluded that each patch material had its own limitations. For example, patch augmentation with glutaraldehyde-fixed autologous pericardium was more prone to patch degeneration, and suture dehiscence was more commonly seen when using the ePTFE membrane. Overall, decellularized xenopericardial patch yielded the best durability, however, a longer follow-up period is required to compare appropriately with autologous pericardium [41].

Other studies have also investigated the utility of different materials in aortic valve repair of various valve morphology. Nezhard et al. compared the repair of various aortic valve malformations with either bovine or non-treated autologous pericardium. They concluded that non-treated autologous pericardium was preferred in easy and less technical repairs, such as perforation patching, and the bovine pericardium was preferred in complex repairs or when autologous pericardium was not available. Overall, the bovine pericardium is comparable with autologous pericardium, however, it still does not compare with native valve tissue and should be avoided if possible [42]. Nordmeyer et al. investigated the durability of decellularized bovine pericardial patch material for aortic valve reconstruction. Despite the reported advantages of the material and excellent short-term results, the authors disagreed with Matsushima and reported concerns regarding long-term durability of the material. Patients with decellularized bovine pericardial patches had thickened leaflets with reduced mobility at 3 years and required further reintervention. Therefore, the search for an optimal patch material is still ongoing [43].

Si et al. addressed the issue of patch degeneration by proposing a bicuspidization unicuspid aortic valve repair with primary leaflet reconstruction and geometric annuloplasty ring repair. They studied patients with aortic regurgitation and attempted to create cusps using primarily the patient's native leaflet tissue. Using this technique supported with an appropriately sized annuloplasty ring, they created cusps with equal free-edge length, geometric, and effective heights. The authors reported excellent results and concluded that most unicuspid aortic valve variations can be repaired using this standard technique. However, the study was limited due to its small sample size and short follow-up durations. More importantly, the repair technique was limited by the smallest available ring size, which is currently around 19 mm, making the technique inappropriate for repair in infants or children [44].

### **3.2 Tricuspidization/reconstruction**

A recently emerging repair technique for unicuspid, as well as bicuspid aortic valves, is tricuspidization by reconstructing all three leaflets [45]. Reconstruction of aortic valves was first proposed by Duran et al.; these authors reported 51 patients with a mean age of 31.2 years who underwent reconstruction of all three leaflets using a single strip of rectangular glutaraldehyde-treated autologous pericardium [46]. Despite some success, the authors concluded that a standardized procedure is needed to ensure technique reproducibility and that further research is needed to determine the best material for reconstruction [46]. Most recent literature includes various valve morphologies in their studies, with the majority being bicuspid aortic valves.

Ozaki et al. proposed another technique that consisted of the reconstruction of each leaflet independently using glutaraldehyde-treated autologous pericardium [47]. This technique is also known as aortic neocuspidization (AVNeo). Since the technique involves complete resection of all three dysplastic leaflets, it can be applied to any congenital aortic valve malformation, even when root reimplantation is required in patients with annulo-aortic ectasia [47]. The authors performed this technique in over 404 patients with unicuspid, bicuspid, tricuspid, and quadricuspid aortic valves. They believe that an aortic valve should be considered as a collection of different-size cusps, and by measuring the distance between the commissure, one should be able to determine the area of each cusp and perform individual cusp reconstruction. With this technique, reconstruction can more effectively preserve the natural motion of the annulus and the coordination between the structures surrounding the aortic valve. At 4 years of follow-up, the survival rate was 87.7% and freedom from reoperation was 96.2% [48]. In another study, Ozaki and associates focused the technique on bicuspid and unicuspid valve morphology in patients under 60 years and noted commendable hemodynamics in all patients, especially those under 40 years. There were also no signs of calcification, as well as natural motion of all three cusps [49]. Ozaki and colleagues later updated their procedure, and the biggest change was seen in the repair of patients without trileaflet aortic valves. They decided that tricuspidization with three equal-size cusps was preferred for an even movement of the cusps [50].

Previously, AVNeo was performed largely in the adult population, where the predominant pathology was acquired calcific aortic stenosis associated with bicuspid valves. In the pediatric population, patients who require further intervention usually are diagnosed with congenital aortic valve stenosis and have previously undergone balloon aortic valvuloplasty resulting in regurgitation. Therefore, since AVNeo requires excision of all leaflets, it is applicable in most pediatric patients as well [45]. The AVNeo procedure was reproduced by Baird and colleagues on the pediatric population with a variety of congenital aortic valve morphologies. Due to the prevalence of bicuspid and unicuspid valve morphology in the pediatric population that

### *Advances in the Management of Congenital Malformations of the Aortic Valve DOI: http://dx.doi.org/10.5772/intechopen.105641*

required intervention, the authors noted technical differences in the pediatric population when creating the 3 equal leaflets. They also highlighted a need to augment the noncoronary sinus leaflet to accommodate 3 equal leaflets creating similar annular and STJ, given the small aortic valve dimensions [51]. Overall, they found satisfactory post-reconstruction hemodynamics and the possibility for annular growth. They also concluded that the Ozaki procedure is promising for pediatric patients, however, it can be technically challenging in patients with smaller aortic annuli and roots and should only be performed by experienced surgeons [45]. Wiggins and associates also utilized AVNeo, as well as a single leaflet reconstruction technique for tricuspidization in pediatric patients who were unable to undergo either a mechanical replacement or the Ross procedure. They were able to successfully perform the procedure in patients with annular sizes as small as 6.7 mm with resultant favorable post-surgical hemodynamics. The authors also commented on the benefit of increased free margin length in AVNeo, and the advantages of preserving annular hemodynamics to allow growth and further reconstruction surgeries if required [22].

#### *3.2.1 Reconstruction materials*

Another controversial topic in the reconstruction of aortic valves is the preferred material for the AVNeo procedure [45]. While autologous pericardium is the most widely used for the procedure due to its availability, convenience, and low cost [4, 52]. Recent studies have shown it to be less favorable due to its poor biomechanical properties, high rates of calcification, and lack of growth potential [4, 45, 51].

The autologous pericardium has been considered the "gold standard" material for aortic valve repair and reconstruction for many decades. Treatment with glutaraldehyde produces autologous pericardium that is more resistant to retraction and degeneration [52]. It can also increase the tensile strength to four times greater than noncalcified native aortic leaflets [50]. However, varying reoperation rates ranging from 15 to 33% have been reported in different studies. Many previous studies focused on the durability of glutaraldehydetreated autologous pericardium in AVNeo performed in the adult population, but its durability in younger patients has not been studied and needs to be further investigated since there is an increased risk of degeneration [22].

The first studies investigating materials for aortic valve reconstruction were by Duran et al., where they compared bovine and autologous pericardium. They determined that autologous pericardium was more favorable as it did not show fibrocalcific deterioration, unlike bovine pericardium. They also concluded that the durability of pericardium will depend on its implanted position and the pretreatment process [53].

Several types of treated bovine pericardium have since been introduced for valve leaflet reconstruction. An example is CardioCel®, where bovine pericardium is treated with glutaraldehyde, as well as by further anti calcification tissue-engineering techniques, prior to reconstruction [45, 51]. Mazzitelli and colleagues utilized CardioCel® for three pediatric AVNeo procedures and reported that there were no reoperations at early follow-up [54]. Despite promising results, long-term follow-up is not available and is needed due to concerns about developing calcification [22, 45, 51]. Another example is the Photofix®, a bovine pericardium that undergoes photo-oxidation fixation. Compared to the glutaraldehyde-treated bovine pericardium, it is more resistant to calcification and inflammation, making it a more durable option. However, Photofix® showed signs of annular separation that are of concern [45, 51]. Lastly, there is also the Matrix®, an untreated equine pericardium, which has shown satisfactory preliminary

results. Furthermore, its thin thickness may be advantageous for smaller pediatric patients [45]. Another interesting theory that is yet to be explored is the remodeling characteristics of extracellular matrix scaffolds. It has been proven in some tissues that degradation occurs due to host remodeling responses to naturally occurring biologic extracellular matrix scaffolds. Hence, durable valve leaflets can potentially be produced if extracellular matrix scaffolds are seeded with mesenchymal stem cells to be differentiated into valve leaflets. However, this theory has yet to be proven [4].

### **3.3 Unicuspid aortic valve: bicuspidization or tricuspidization?**

In unicuspid aortic valves, it is debatable whether a symmetrical bicuspidization technique is superior to a tricuspidization method. This may have been related to the variability in commissural height and interrelation of three coaptation lines in tricuspid aortic valves [39].

Kawase et al. performed trileaflet reconstruction on 9 unicommissural unicuspid aortic valve patients. They utilized glutaraldehyde-treated autologous pericardium to independently construct each leaflet so that coordination of the valve leaflets is maximized. These authors reported that tricuspidization is superior to bicuspidization as it produces a longer total length of the free margin of the aortic valve leaflets, resulting in a better full opening of the aortic valve. However, the study was only performed on adults with a mean age of 48.9, and the average follow-up time was 18 months. Hence, a larger and wider study population, and long-term results are needed [38]. Kohei and associates discussed tricuspidization of 2 patients with unicuspid aortic valves and performed aortic valvuloplasty and root construction using autologous pericardium and a prosthetic graft. They agree that bicuspidization is hemodynamically inferior to tricuspidization as it adds stress to the leaflets and restricts opening. However, longterm results are also unavailable to determine the durability of this approach [55]. Therefore, it appears that tricuspidization is an area of repair that yet to be explored for unicuspid aortic valve repair. Both studies discussing tricuspidization techniques were performed on adults with a small sample size, hence durability results in pediatric population and long-term results are lacking.
