**6.1 Pure aortic regurgitation**

Moderate to severe aortic regurgitation has a prevalence of 0.5%. The course of chronic aortic regurgitation leads to left ventricular dilation and heart failure. Primary aortic regurgitation may be caused by infective endocarditis, rheumatic disease, or degenerative/calcific valve disease. Bicuspid aortic valve, while more commonly associated with stenosis, may cause pure aortic regurgitation or a mixed disease. Aortic regurgitation may also be secondary to marked dilation of the ascending aorta [84].

The gold standard treatment is surgery, with both aortic valve replacement or aortic valve-sparing root replacement. Currently, the role of TAVI is limited to selected patients with aortic regurgitation deemed ineligible for SAVR [13, 85].

The commercially available TAVI devices have been designed for the treatment of degenerative calcific aortic stenosis. The presence of a rigid frame of calcium in the annulus provides an anchoring point for device deployment. The lack of calcium poses thus a significant challenge, as there is increased risk of device malposition, dislodgment, and embolization. The lack of calcification may also lead to higher rates of PVL. Another issue is the risk of implanting undersized devices, as regurgitant aortic valves are more elastic than calcific stenotic valves and can expand to a greater degree during valve deployment. Furthermore, the concomitant presence of a certain degree of aortic disease with dilation and friable tissues poses a further degree of risk for the procedure [85, 86].

Registry data show that TAVI in pure aortic regurgitation has worse outcome than TAVI in aortic stenosis. A 331 patients registry showed a 3% rate of procedure-related death, a 3.6% conversion to open surgery, a 1.2% rate of coronary obstruction, a 1.5% of aortic root injury, and a 16.6% need for second valve implantation. Newer generations valves scored better, as device success went from 61.3% to 81.1% (p < 0.001) and moderate to severe aortic regurgitation decreased from 18.8 to 4.2% (p < 0.001). [85] In another registry, also including patients with failing bioprosthesis, device success was achieved in 85% of patients with newgeneration devices [87].

New prosthesis specifically designed for aortic regurgitation are currently being investigated, such as the Trilogy Heart Valve (Trilogy; Jena Valve Technology), which features anchor rings to clasp the native aortic leaflets [88]. While TAVI may be an alternative for selected patients deemed at high risk for surgical aortic valve replacement, it is currently an off-label indication; randomized control trials and long-term data are still needed.

#### **6.2 Bicuspid aortic valve stenosis**

The bicuspid aortic valve is the most common congenital heart defect, with an incidence of around 1% [89]. Almost half of the patients undergoing isolated aortic valve replacement have a bicuspid aortic valve, with a higher incidence in younger patients [90]. In the contemporary practice, up to 10% of patients with bicuspid aortic valve stenosis are referred to TAVI [91].

Echocardiography often underestimates the prevalence of bicuspid valves in calcified aortic stenosis [91]. CT scan provides a more accurate diagnosis and visualization of the bicuspid morphology [92]. Bicuspid aortic valve encompasses a wide range of morphologies; the most common classification categorizes it according to the number of raphes [93].

Aortic annuli in patients with bicuspid valve tends to be larger than in patients with a tricuspid valve. The annulus size may be outside of the range for the currently available devices. Furthermore, the aortic valve complex may have a non-tubular geometry, such as tapered or funnel anatomy. This adds complexity to the selection of a compatible prosthesis [94].

Bicuspid valves have a higher calcific burden than tricuspid stenotic valves. The calcium involves the leaflets in an asymmetrical way and often extends to the LV outflow tract. The majority of the bicuspid valves have a fibrotic and calcified raphe. These anatomic elements hinder the optimal expansion of the valve during TAVI. The asymmetric expansion of the prosthesis increases the risk of PVL. The presence of a highly calcified raphe, if localized between right coronary cusp and non-coronary cusp, increases the risk of conduction disturbances. Calcified raphe and excess leaflet calcification have been found to predict all-cause mortality in TAVI, and when both were present patients had higher rates of aortic root injury and PVL [94, 95].

In addition, coronary anomalies are more frequent in patients with bicuspid aortic valve, and 20 to 30% of them have concomitant aortic disease [89, 94]. Many patients may need aortic root surgery in addition to the valve replacement.

Data about the outcome of TAVI in bicuspid valve anatomy are limited to observational studies, as it was an exclusion criterion in all the randomized trials confronting TAVI with SAVR. In patients at increased surgical risk included in the STS/ ACC transcatheter valve therapy registry (STS/ACC TVT Registry; NCT01737528), TAVI for bicuspid aortic valve stenosis showed acceptable safety outcomes with low complications rates [96]. When current-generation devices were used, device success was higher (96.3 vs. 93.5; P = 0.001) and the incidence of moderate to severe PVL was lower (2.7% vs. 14.0%; P < 0.001) in comparison with older-generation devices. With current-generation devices, device success was slightly lower in the bicuspid valve group (96.3% vs. 97.4%; P = 0.07) in comparison with tricuspid stenosis, with a slightly higher incidence of residual moderate or severe PVL. A comparable 1-year mortality was observed, with no increase in the risk of stroke [97]. Results of TAVI in low-risk patients with bicuspid valve anatomy seem similar to those patients with tricuspid aortic valve. In the PARTNER 3 bicuspid registry, with a population of 169 patients, a propensity score matching with TAVI patients showed no difference in the primary endpoint and in the individual components (death, strokes, cardiovascular rehospitalization). Of note, almost half of the patients submitted (47%) were not treated, being excluded because of anatomic or clinical criteria [98]. Another small prospective trial showed good short-term outcomes in low-risk patients with bicuspid aortic valve [99]. Despite the good outcomes in selected patients with favorable anatomies those results cannot be inferred for all the patients with bicuspid aortic valve.

Technical recommendations for TAVI include more frequent balloon valvuloplasty and post-dilation, a low degree of oversizing, and the use of repositioning prosthesis. In tapered anatomies, a supra-annular positioning of the prosthesis has been suggested [94].
