Various Endoluminal Approaches Available for Treating Pathologies of the Aortic Arch

Open surgical repair of the aortic arch for degenerative aortic disease in an unfit patient is associated with significant morbidity and mortality. Endoluminal techniques have advanced over the last decade. Contemporary endovascular options including a hybrid approach (supra-aortic debranching and aortic stent graft), inner branched endograft, chimney stents, and scallop or fenestrated endografts are being used frequently as an alternative to open surgical arch repair. Understanding of the available endoluminal technology along with careful planning and effective teamwork is required to minimise complications associated with the endoluminal techniques, particularly neurological ones. Custom made techniques are superior to chimney or parallel technology in terms of their complications and durability. Integration of the protective devices such as embolic protection filters into stent design may reduce the risk of poor neurological sequelae. Long-term data are needed to assess the durability of these devices.


Introduction
Over the last decade, significant progress has been made in the treatment modalities for the aortic arch diseases. Open surgery is still considered the gold standard in young and fit patients as well as in patients with genetic aortic syndrome. Open aortic arch repair requires cardiopulmonary bypass, deep hypothermal circulatory arrest and antegrade or retrograde cerebral perfusion. Cardiopulmonary comorbidities frequently exist in patients with degenerative aortic disease which increase the overall mortality and morbidity with the open repair. Comparable perioperative mortality and stroke rates have been reported between the endovascular arch repair and open arch repair, despite the older age and a higher comorbid profile of patients in the endovascular group [1]. Elective and emergency open repair of arch pathology carries mortality risk of 9% and 37%, respectively [2]. This review focuses on contemporary endovascular options for the treatment of aortic arch pathologies which include hybrid approach (supra-aortic debranching and stent graft), inner branched endograft, chimney stents, and scallop or fenestrated endografts. 8 Spinal cord ischemia is a potential serious complication, especially in cases where left subclavian artery is sacrificed. Prophylactic CSF pressure monitoring and drainage especially in cases of extensive aortic coverage with a target CSF pressure between 10 and 12 mmHg is considered a protective measure 9 Unfractionated heparin is needed during endovascular repair to prevent risk of thrombotic complications. Dose of the heparin can be variable depending on factors such as patient's weight, underlying thrombotic/ bleeding risks and duration of the procedure. Activated clotting time (ACT) should be performed in theatre. ACT [3,5].

Key Principles to Remember While Planning Endoluminal Intervention for Aortic Arch
The complexity of stent design, anatomical difficulties, the inherent high risk of neurological complications and complex hemodynamic forces in the ascending aorta and aortic arch are the main challenges facing endovascular intervention in this part of the body. Thorough anatomy assessment and careful planning of the procedure using high-quality cross-sectional computed tomography angiography with thin axial slices for multiplanar reconstruction are essential prerequisite for planning complex arch procedures. This should be accompanied by a wellcoordinated teamwork preparation. Adequate access vessels for the main device and for fenestration or branched or chimney stent placement are crucial. Femoral access is used for the deployment of the main arch device. Heavy calcifications in the iliac or femoral arteries may restrict the delivery of the stent graft. Construction of an iliac conduit may be required to allow the safe passage of a 20-25 French sheath. Percutaneous or open femoral access is at the discretion of the operator, but a scarred groin from previous surgery may make access challenging. Where brachiocephalic access is required, it can be achieved percutaneously via the right brachial or axillary route or open exposure of the right common carotid artery. Access to the left carotid artery is obtained by surgical exposure. Anatomically, increased arch angulation, minimum length for seal and irregular landing zone demand good stent design and material for adequate conformability with minimal change in aortic stiffness. Excessive mural thrombus and calcification together with proximity to the aortic valve increase the risk of embolisation. Careful and minimal wire and device manipulation is essential. Air emboli from the delivery system of the stent graft are a risk factor for stroke, and CO 2 flushing has been proposed to prevent that risk [6]. However, more evidence is needed to prove that combined CO 2 and saline flushing helps preventing air emboli before routine application of this technique is recommended. The risk of early mortality is higher in Ishimura zone 0 landing as compared to zone 1 or 2 [7]. Please see Fig. 1 for details about the Ishimura zones in the aortic arch [8]. It is important to perform the procedure using advanced imaging to avoid excessive radiation, reduce contrast volume and ensure accurate device placement and vessel cannulation. Transoesophageal

Prediction for the Future
In the years to come, endoluminal techniques will increasingly be used in treating aortic arch pathology. Further refinement of stent graft material and characteristics is necessary, including cerebral protection devices integrated into the endograft device, proved measures to reduce air emboli and lower profile of delivery system and bridging stents *Angulation is measured by the type of the arch and the radius of curvature (ROC) which is measured at the closest edge of wall of ascending aorta to adjacent closest edge of descending thoracic aorta (at the level of the pulmonary artery bifurcation) [37] echocardiogram can be an adjunctive tool during endovascular cases for guidewire placement in the dissected aorta or endoleak assessment [9]. Various monitoring tools have been used in open surgery for assessment of cerebral or spinal cord ischaemia including near infra-red spectroscopy, electroencephalography and motor or sensory evoked potentials. Evidence is lacking for their use in endovascular arch repair, but they can be used in selective endovascular cases (depending on the resources, the urgency of operation and the extent of the coverage of the aorta) [10]. Please see the fact sheet page for important anatomical parameters for endoluminal case planning.

Endovascular Treatment Modalities Hybrid Repair
Hybrid repair of aortic arch pathology involves replacing one, two or all three supra-aortic vessels (debranching of the supra-aortic vessels) to create a sealing zone of healthy aorta of at least 2 cm in length, followed by thoracic endovascular aortic repair (TEVAR) stent placement in the arch, either staged or simultaneously. Several options exist for performing debranching including carotid to carotid bypass, left carotid to left subclavian artery (SCA) bypass or total arch debranching with fashioning of neoinnominate artery (see Fig. 2). Total arch debranching requires median sternotomy, and the graft is taken from the proximal ascending aorta. A staged procedure is our preferred option with debranching done first, followed by the TEVAR stent a week or two later. Arch disease involving zone 2 or 3 is better suited for hybrid repair with extra-anatomically carotid to carotid or left carotid to left SCA bypass, respectively. For arch diseases involving zone 0 or 1, total debranching of the arch vessels followed by endovascular stent landing in zone 0 is recommended. The hybrid procedure has the advantage over open arch repair in high-risk patients as there is no aortic cross-clamping involved and no requirement for cardiopulmonary bypass in most cases. Endografts available for this purpose are those used in descending aortic diseases, including RelayÒ PLUS (Terumo Aortic US Bolton Medical Inc), Conformable . The stroke risk following hybrid repair is significant reported at 28.6% in one study [11]. A meta-analysis involving 1,186 patients who underwent aortic arch hybrid repair reported mortality, stroke and spinal cord ischaemia rates of 10.8%, 6.9% and 6.8%, respectively [12]. The risk of spinal cord ischaemia is higher in cases of extended thoracic coverage. Maintaining a good peri-operative blood pressure, performing hybrid procedures in stages and revascularisation of the left SCA are considered to reduce the risk of spinal cord ischaemia. Dissection of the supraaortic vessels carries risks of nerve injury (phrenic and vagus nerves) and lymph leaks. The presence of heavy calcified plaque, mural thrombus in the arch, and inadequate length of landing zone are some of the limitations for hybrid thoracic aortic stenting.

Total Endovascular Approach
Technologies have evolved over the last decade and, in selected cases, can now provide a complete endovascular solution for aortic arch diseases in patients who are at high risk for open surgery. The surgery duration and the length of stay in the intensive care unit are significantly less in endovascular group as compared to open surgical repair [13]. Total endoluminal strategies involves custom-made devices with fenestration, scallop, inner branched endografts and parallel (chimney) endografts.

Fenestrated/Scallop Endografts
Custom-made fenestrated or scallop stent grafts are manufactured using the standard stent graft platform. The fenestration or scallop is placed against the target vessels, extending the proximal landing zone without compromising the great vessels. They are suitable in cases where disease involves zone 2 and 3. Fenestrated arch devices have either single fenestration or a combination of fenestration and scallop, or a scallop alone (see Figs. 3 and 4). Figure 5 shows the schematic illustration of the scalloped and fenestrated endograft. The aorta must be nonaneurysmal at the level of fenestration or scallop and the ostia of the vessels at the outer curve of the arch should be along one line. The pre-curved nitinol cannula of the delivery system allows spontaneous orientation of the device. Commercially available devices are the Zenith fenestrated arch graft (COOK Medical, Bloomington, IN, USA) and Relay Ò(Terumo Aortic US Bolton Medical Inc.). The Cook Fenestrated endograft has been reported safe and technically feasible with mortality up to 9%, stroke risk of 9%, temporary spinal cord ischaemia rates of 7% and early reintervention rates of 7% [14]. Please see Table 1 for the detailed results of some of the studies on endoluminal techniques. The Bolton RelayÒ scallop and/or fenestrated endograft can be used in any zone and has shown high technical success and low 30-day mortality. In two small single-centre series, the incidence of stroke ranged from 0-14% and endoleak from 10-19%. There was no evidence of migration or branch occlusion [15,16]. The Dutch registry of 23 proximal scallop patients reported a 91% technical success rate. The incidence of clinical stroke and paraplegia was 4%. There was 2/23 and 1/23 type 1 and type 2 endoleaks, respectively, with no aneurysm-related death or growth over a mean follow-up time of 9 months [17]. of follow-up with an 8% late reintervention rate to treat two cases of type 1a and one case of type 2 endoleaks. The authors consider fenestrated and /or scallop grafts in cases with saccular aneurysm along the inner curve of the arch, or cases with borderline length landing zone where proximal extension and inclusion of one or sometimes two great vessels will obviate the need for hybrid repair. The deployment of fenestrated or scallop endografts is relatively simple due to the pre-curved inner cannula, allowing self-orientation of the device with little manoeuvring by the operator.

In Situ Fenestration of the Standard Stent Graft
This is an off-label technique used in emergency settings, in which a fenestration is made in the stent graft by mechanical means or laser technique. The fenestration is sequentially dilated with balloons and finally, a stent is placed across the fenestration into the target vessel, usually from peripheral access in a retrograde manner. Qin et al. reported laser-guided fenestrations in 24 cases of aortic arch stent grafts with 16/24 fenestrations for left SCA alone and only 2 for all three arch vessels. Technical success was reported at 95.8%, with no endoleak or stroke [18]. The main risks associated with this technique are technical failure which can damage the graft and cause type 3 endoleak and risk of end-organ ischaemia (particularly brain ischaemia) due to the time taken in performing the fenestration. No long-term data are available and the risk of damaging the stent graft has not been extensively studied [19].

Arch Branched Grafts
Two main designs of branched endografts are available so far in the market: one device with two antegrade internal tunnels, and a second design with a retrograde single branch. The first type from Cook Medical (Cook Medical, Bloomington, IN, USA) and Bolton Relay Plus (Terumo Aortic, Sunrise, FL, USA) has tunnels with antegrade flow towards the brachiocephalic trunk and left carotid. Access for the left carotid branch is gained retrogradely from left carotid puncture, while access to the innominate branch is obtained retrogradely from either the right common carotid or axillary artery. Depending on the stent manufacturer and native vessel diameter, the profile of the bridging stent for the brachiocephalic inner branch ranges from 9 to 14 F and cutdown is usually needed. The profile of the bridging stent for the left carotid inner branch is usually 6-8F, and open access is usually obtained over the left common carotid artery. The main thoracic stent graft is deployed from the femoral artery access over a stiff wire, the tip of which is placed in the apex of the left ventricle. A pigtail angiographic catheter is placed near the sinotubular junction. Rapid pacing or an inferior vena cava balloon is required to reduce the cardiac output down during deployment. The profile of different branched stent grafts is provided in Table 2. The delivery systems of both the COOK and Bolton Relay devices are similar and come with a precurved nitinol inner cannula which helps orientate the branches along the outer curvature of the aortic arch. The Cook graft delivery system also has multiple trigger wires which helps in controlled deployment. The branched graft usually lands further proximally in the ascending aorta than the fenestrated graft (see Fig. 6). Please see Fig. 7 for a schematic illustration of arch branched endograft with two  antegrade tunnels. Arch branch endograft is suitable for aortic pathology where involving zones 0, 1 and sometimes 2. The limitations of these devices are a required landing zone length of at least 4.5 cm in the ascending aorta, a maximum native diameter vessel of 38 mm, and the inability to use them in the presence of metallic aortic valve. Please see Previous surgical repair for type A dissection can provides an excellent landing zone for branched endograft, as this eliminates risk of retrograde type A dissection completely provided that the interposition graft has an adequate length. A series of 30 consecutive patients with a range of arch pathologies treated with branched stent graft from Cook reported 90% technical success, 7% neurological events, 30-day mortality of 10% and reintervention of 20% [20]. These results showed improved outcomes when compared with a previous multicentre study of 38 patients that reported 13% mortality and a stroke rates of 16% (Please see Table 1) [21]. Recently, a single centre experience of custom-made inner branched arch endograft with two internal branches (Cook Medical, Bloomington, IN, USA) and left-sided carotid to SCA bypass of 54 consecutive patients has reported a technical success rate of 98% and a 30-day mortality and major stroke incidence of 5.5% and 5.5%, respectively [22]. However, neurological events, a mixed of disabling and non-disabling stokes, were observed in around 20% of patients [23]. In-hospital mortality was 7%, with 100% aorta-related survival over median follow-up of 263 days. The Inoue device (PTMC Institute, Kyoto, Japan) is a custom-made all-in one stent graft with aortic stent section and branched section sewn together. It comes with a mixed number of branches. The largest series of 89 patients treated with the Inoue device showed high technical success and a low 30-day mortality of 4.5% but high stroke rate of 16% [24].
A different branched design is available from Gore & Associated (Gore Medical Flagstaff, AZ, USA), whereby a retrograde single branch is assembled into the Conformable TAG device. The Gore graft is designed for zone 0 or 2. Patel et al. reported early results of a multicentre study of 24 patients with aneurysmal disease treated with a single branch stent graft to the left SCA. The technical success and survival rates were 100% with no reported stroke in this small and highly selected group [25]. Another single retrograde side branch endograft, Valiant Mona LSA (Medtronic Inc Santa Rosa CA USA), has also been investigated. These are usually suitable for zone 2 or more proximal zones where they are combined with extraanatomical bypass. Both the Gore and Valiant systems have a preloaded catheter inside the branch, which is threaded and requires snaring from the brachial, axillary or carotid access in the arch and deployment over the throughand-through wire. Please see Table 2 for the details of different arch branched devices.
Overall technical results are particularly good with both branched and fenestrated arch devices. These should be considered in patients who are not fit for open repair. The arch branch technique provides a durable repair as the landing zone is in the ascending aorta. However, the procedure itself is complex and not possible if the ascending aorta is aneurysmal. In our experience, we consider arch branch technology for pathology in zones 0-2, when the great vessels are not suitable for scallop or fenestration because of vessel alignment or inadequate landing zone, and unfit patients with reasonable life expectancy.

Chimney Grafts/Parallel graft/Periscope
The concept of parallel chimney stents was initially described as a ''bailout'' technique after inadvertent renal artery coverage during endovascular abdominal aortic repair [26]. The direction of flow is antegrade in a chimney graft and retrograde in periscope technique. The main aortic stent is inserted via femoral access into the pre-defined place in the thoracic aortic arch. Via retrograde approach from the common carotid or arm access (axillary or brachial), the chimney grafts are positioned parallel to the aortic stent-graft and protruded around 1-2 cm proximal to the main aortic stent with the distal stent segment sitting in the branched vessel. The main TEVAR and the chimney stent are deployed sequentially and may be moulded with a balloon (see Fig. 8). For carotids chimney stent, access is achieved via surgical cutdown in the neck. Commonly used stents for the chimney are Fluency (C.R. Bard, Inc, Murray Hill, NJ, USA), ViabahnÒ (W.L. Gore, Inc., Flagstaff, AZ, USA), Atrium (Maquet Getinge Group, Inc., Germany) and Bentley. For a large diameter innominate artery, iliac endograft limbs (such as Zenith FlexÒ TFLE/ZSLE; Cook Medical, Inc., Bloomington, IN, USA) can be used as chimney stents. It has been technically feasible to use this technique into supra-aortic branches parallel to the main aortic stent graft for aortic arch diseases [27,28]. Balloon expandable stents are preferable to self-expanding due to their accurate deployment and higher radial force [29]. Chimneys are mostly performed for acute emergency reasons such as dissection, IMH and pseudoaneurysm, with the commonly used proximal landing zone site is in zone 2, and frequently done for a single vessel [30]. This technique is relatively cheaper to use, and it is perceived as less technically demanding [7]. Other examples of parallel graft are periscope and sandwich techniques. A periscope graft is inserted from femoral access into the supra -aortic vessel, usually the left SCA, or inserted retrogradely from the SCA vessel into the descending aorta. The periscope endograft sits parallel to the main aortic graft and extends distal to the thoracic aortic stent graft. The sandwich technique involves placing the target artery stent between two overlapping thoracic aortic stents.
O'Callaghan retrospectively compared custom made fenestrated endograft (n = 15) against non-custom-made chimney stent (n = 18). In hospital mortality was higher in non-custom group (7 vs 18%). There was a trend noted favouring better durability of fenestrated graft for sealing and re intervention rates but results were not statistically significant [31]. One of the most debated down sides of the chimney stent graft is the risk of type 1 endoleak and endotension due to the gutter effect between the aortic endograft and the chimney graft, raising doubts over its durability. It has been suggested that the risk is higher when the pathology involves the outer curvature of the aorta than the inner curvature of the aorta [32]. A European multicentre registry on the chimney or snorkel technique reported the outcomes of 95 patients. Technical success was achieved in 89.5% of cases, with 9.5% 30-day mortality and 10.5% type 1a endoleak. Freedom from intervention at 5 years was 88.6% [27] (please see Table 1). A meta-analysis of 11 publications involving 373 patients who underwent chimney endografts for their aortic arch disease (reported overall technical success rates of 91.3%, overall estimated proportion of early type 1a endoleak of 9.4% and retrograde type A dissection of 1.8%. The reported pooled 30-day mortality was 7.9%, with a reintervention rate of 10.6% and major strokes rate of 2.6% [30]. No long-term data exists regarding the durability of the chimney graft in the aortic arch. An overlap of at least 2 cm between the chimney and the thoracic stent-graft, adequate oversizing of the thoracic stent-graft (30%) except in acute dissection and kissing balloon angioplasty in the chimney and aortic stent-grafts simultaneously, with rapid inflation/deflation and moderate inflation pressure may decrease the risk of endoleak. In our experience, we reserve the use of chimney for emergency cases and as a bailout in inadvertent cover of a great vessel. We tend to oversize the TEVAR stent by at least 15-20%, attempt to extend the tunnel length more than 25 mm and limit the number of chimneys to one whenever possible. The double chimney technique carries much higher rates of complications including type 1 endoleaks and its use is controversial [33].
Please see the fact sheet for some of the important papers underlining the key evidence regarding the endoluminal techniques in aortic arch repair.

Complications Associated with Endoluminal Techniques
Generic complications associated with endoluminal technique for the aortic arch include the risk of arrhythmias and myocardial ischaemia due to the close proximity of the wire or sheath to the coronary ostia and left ventricles. Cardiac complications including acute coronary syndrome and arrhythmias have been reported in the range from 4.3 to 7.9% [21,34]. Cardiac perforation by the stiff wire is a recognised complication and must be avoided by careful wire manipulation. Access site complications are not uncommon and occasionally requires re intervention for pseudoaneurysm and arterial repair. Verscheure et al. reported 11.4% access site complications requiring intervention [34]. Temporary renal impairment is common, and care should be taken in the use of contrast. Moreover, any nephrogenic medications such as metformin should be withheld for 48 h after the procedure. Wound infection, nerve injury and lymph leak are rare but known complications associated with surgical cutdown. team-based approach must be taken in choosing individualised treatment for the patient based on patient's pathophysiology, anatomical features of the arch and the experience of the team. Custom-made branched, fenestrated or scalloped endoluminal techniques should be preferred over the chimney technique for elective repair of the aortic arch. The chimney technique should be reserved as a bailout approach for emergency cases. We may see developments in new technologies, including in situ fenestration techniques, over the coming years.
Acknowledgements This study was supported by Imperial College London Healthcare Biomedical Research Centre.
Funding The study was not supported by any funding.

Compliance with Ethical Standards
Conflict of interest MH received honorarium and educational grants from Gore & Associates and Terumo Aorta.

Ethical Approval No ethical approval required for this type of study
Informed Consent For this type of study informed consent is not required.

Consent of Publication
For this type of study consent of publication is not required.
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