*1.4.7 Valve choice and implantation*

The type of transcatheter heart valve is extremely relevant, and the use of a recapturable self-expanding transcatheter heart valve can be beneficial. Clinical and angiographic assessment of coronary flow after deployment can be performed prior to complete release or retrieval of transcatheter heart valve performed in the setting of coronary occlusion to restore flow. Certain newer transcatheter heart valve devices possess clipping mechanisms enabling grasping of surgical leaflets, thus preventing coronary obstruction [83]. Intentional implantation of a smaller transcatheter heart valve or under expansion of a balloon-expandable transcatheter heart valve reduces the lateral movement of surgical valve posts and leaflets, thereby decreasing chances of coronary obstruction, as does, low-depth transcatheter heart valve implantation compared to high-depth implantation, although the risk of elevated post-procedural gradients may be increased with the latter.

### **1.5 Valve thrombosis**

Sub-clinical leaflet thrombosis is a worry that continues to surround TAVR and ViV-TAVR. The potential need for anti-coagulation is important to patient choice and lifestyle. It is defined as the presence of reduced leaflet motion associated with CT proven hypoattenuating lesions and is associated with a greater risk of transient ischemic attacks [84]. The effects on patient outcome and long-term valve performance remain unclear [85, 86]. A variety of causes are responsible for leaflet thickening and impaired leaflet motion, including leaflet thrombosis, infection and leaflet degeneration [16]. Both TAVR and SAVR are affected by a reduction in leaflet motion, and the incidence is reported as 4% and 13%, respectively [84]. Currently, no robust randomised evidence exists guiding antiplatelet versus anti-coagulation use after ViV-TAVR.

#### *Valve-in-Valve Transcatheter Aortic Valve Replacement: Challenges for Now and the Future DOI: http://dx.doi.org/10.5772/intechopen.112764*

The appropriate treatment of sub-clinical leaflet thrombosis is unclear with evidence showing that it may regress spontaneously. Up to 25% of patients on antiplatelet therapy display this phenomenon, with oral anticoagulants showing efficacy in both its prevention and regression with associated improvement in valve gradients [86–88].

Whether sub-clinical leaflet thrombosis translates into an increased number of thromboembolic neurological events is unclear, but it appears to be associated with elevated valve gradients [89]. ViV-TAVR patients are likely to be at a high risk of leaflet thrombosis due to lesser haemodynamic performance and suboptimal blood flow patterns associated with low implant depth and turbulent blood flow patterns between new transcatheter heart valve leaflets and degenerated valve leaflets [90, 91]. Valve design affects propensity towards leaflet thrombosis, with certain valve types more prone than others [88]. For this reason, a more stringent anti-coagulation regimen has been recommended following ViV-TAVR particularly in patients with elevated thrombotic risk [92]. The issue of possible anti-coagulation for ViV-TAVR is hugely important especially in patents with extended life expectancy and remains unresolved. It is likely that the need for anti-coagulation will be a patient specific, bespoke decision based on anatomical and patient-related risk-factors.

#### **1.6 Cerebral embolism**

Transient ischaemic attacks and cerebrovascular accidents are a dreaded complication of any aortic valve intervention, and cerebrovascular accident remains an independent risk factor for death after TAVR [93]. Embolisation is the primary aetiopathogenic mechanism, although the pathogenesis is well known to be multifactorial. The rate of silent embolic lesions following TAVR approaches 80%, and anything that can be done to mitigate this phenomenon is welcome. Despite this, fortunately the incidence of new, persistent clinical neurological injury is only 3–6% [94, 95]. Cerebrovascular accident rates continue to decline after TAVR, but attention is still focussed on strategies to reduce this further [86]. Luckily, the incidence of major stroke following ViV-TAVR has been reported at less than 2% [41], and recent meta-analysis shows no discernible difference in 30-day stroke rate and mortality among ViV-TAVR, TAVR and redo-SAVR [96].

The main proposed factors influencing cerebrovascular accident/transient ischaemic attack risk include atrial fibrillation, acute and sub-acute thromboembolism stemming from the transcatheter heart valve, aortic debris and device instrumentation [81]. Cerebral embolic protection devices are evolving and have been mainly studied during TAVR on native valves. They have shown efficacy in reducing cerebral emboli load, without any effect on short-term cerebrovascular accident or 30-day mortality rates or hospital length of stay [97]. Despite these findings, consideration of the use of cerebral embolic protection devices during ViV-TAVR planning is important, especially where significant instrumentation or technical difficulties are anticipated.

#### **1.7 ViV-TAVR in the young**

The patient with aortic stenosis and a long life expectancy that exceeds the durability of a bioprosthesis must be managed very carefully by the heart team, as "optimal" first intervention is paramount. Future negative and positive effects of any bioprosthesis must be anticipated and the anatomy of the aortic root appreciated fully at first intervention. The heart-team approach is an integral part of valvular discussions in patients with severe aortic stenosis and will likely gain increasing importance in the future. A distinct shift of focus towards lifetime management is now occurring after the approval of low-risk TAVR.

Treatment options in younger patients is attracting considerable debate. For those that elect to undergo SAVR, the options for structural valve deterioration are ViV-TAVR or redo-SAVR. For those that undergo TAVR, the options for structural valve deterioration include TAVR explant with SAVR or TAVR-in-TAVR. Of huge importance, many patients with longer life expectancy or early valve failure may need a third valve intervention. A multitude of anatomical scenarios are likely to now be encountered and have to be adjusted for. In patients who are candidates for TAVRfirst, transcatheter heart valve with a short frame and large open stent frame cells may be better within the context of large aortic roots and high coronary ostia, in patients with favourable anatomy for future TAVR-in-TAVR implantation [72, 98]. Whereas in patients with low coronary ostia and small aortic roots, TAVR-in-TAVR will be more problematic and therefore SAVR-first with bioprosthesis with as large an orifice as possible plus/minus aortic root enlargement may be better, followed by future ViV-TAVR [99].

#### *1.7.1 SAVR-first strategy*

As discussed in detail earlier, ViV-TAVR is associated with better short-term outcomes than redo-SAVR [100]. However, the long-term durability for ViV-TAVR is still unclear. Encouragingly, at mid-term follow-up, <10% of patients display clinically significant structural valve deterioration [101, 102]. Coronary obstruction, difficult re-access to coronaries, severe patient prosthesis mismatch and unclear need for anti-coagulation are residual ongoing concerns surrounding ViV-TAVR. The serious complication of coronary obstruction requires advanced techniques for coronary protection such as chimney stenting or BASILICA, both of which are not simple and increase procedural risk [103, 104]. Rates of paravalvular leak are low but significantly higher than redo-SAVR [19]. Intriguingly, after ViV-TAVR failure, the potential for repeat ViV therapy may be possible, if aortic root diameter allows [105].

#### *1.7.2 Summary of factors favouring SAVR-first policy in young, low-risk patients*

Young, low-risk patients often have high anatomical risks such as bicuspid aortic valves, severe annular calcification and low coronary heights. The long-term patient impact of increased permanent pacemaker use and paravalvular regurgitation, along with long-term transcatheter heart valve durability, remain unknown.

Leaflet thickening and coronary re-access remain significant concerns surrounding TAVR.

Valve choice in this group for SAVR also becomes important for the life-time management of aortic valve disease. The largest SAVR valve should be implanted, ideally not less than 23 mm with root enlargement if required. Implanting surgical valves which are prone to fracture for future optimisation of ViV-TAVR is also relevant for this sub-group of patients. The Edwards Inspiris Resilia valve has built-intechnology which enables easy expansion of the valve annulus, and other new generation "TAVR ready" surgical valves will no doubt follow from other manufactures.

*Valve-in-Valve Transcatheter Aortic Valve Replacement: Challenges for Now and the Future DOI: http://dx.doi.org/10.5772/intechopen.112764*

#### *1.7.3 Redo SAVR*

Being more invasive, it is not surprising that short-term outcomes following redo-SAVR appear inferior to ViV-TAVR [102], but longer-term, major cardiovascular outcomes appear the same [102]. As discussed earlier, no randomised prospective data directly comparing the two techniques are available and are greatly needed. Redo-SAVR is much more invasive than ViV-TAVR but is considered by many as the more complete intervention. In well-selected patients, excellent outcomes with excellent freedom from intervention at 10 years is achieved [106–108], with less incidence of severe patient prosthesis mismatch, leaflet thrombosis and paravalvular leak [19]. Another perceived advantage is that redo-SAVR "resets" the clock and again facilitates the possibility of ViV-TAVR as a potential third intervention if needed.

#### *1.7.4 TAVR-first strategy*

#### *1.7.4.1 TAVR explant and SAVR*

As summarised above, the TAVR-first strategy in young patients has raised concerns from a wide group of people as doubts remain relating to permanent pacemaker rate, paravalvular leak rate, long-term durability of the TAVR valves and possible need for anti-coagulation [109]. These doubts are more striking when the excellent longterm durability, outcomes and robustness of the anatomical SAVR are used for comparison. TAVR explantation rates are increasing. Most cases have been performed due to unsuitability for the ViV-TAVR procedure and often need extensive surgery and are associated with mortality as high as 15% [110–112]. Sometimes, longer-term TAVR explants require extensive aortic endarterectomy and/or aortic root or ascending aortic replacement. Surgical explantation of SE TAVR valves is more complex and high risk than balloon-expandable TAVR valves. The self-expanding stent can be incorporated into the aortic root and require more extensive surgical procedures. Therefore, TAVR explant mortality rates have been elevated [110]. Surgical expertise is limited in this unique type of surgery and with time is likely to increase and may lead to improved mortality rates during surgical re-intervention for primary TAVR [111].

As mentioned earlier, another perceived advantage of this strategy is SAVR as the second intervention in anatomically suitable patients allows the third potential intervention if needed to be ViV-TAVR in a surgical valve.

#### *1.7.5 TAVR-in-TAVR*

TAVR-in-TAVR appears safe, but longer-term data and larger series are needed [113]. Concerns remain about durability and higher rates of paravalvular leak and valve thrombosis and the need for anti-coagulation [84]. In addition, it is believed that many patients will not be suitable for TAVR-in-TAVR because of anatomical constraints centred around the risk of coronary obstruction and coronary re-access [98]. The options for coronary protection are more limited with TAVR-in-TAVR and are a major concern if this strategy is to be employed widely in a large number of younger patients. Recent development of "balloon-assisted BASILICA" shows promise, but it is complex and requires more investigation and refinement [114].

One positive finding is that because of its greater ability to overexpand the transcatheter heart valve, a greater internal orifice diameter is achieved following TAVR-in-TAVR than ViV-TAVR in a surgical valve, leading to less incidence of high gradients [113].
