Non‐A non‐B aortic dissection: A literature review

Non‐A non‐B aortic dissections are an infrequent occurrence and represent a small proportion of aortic dissections. Treating this life‐threatening medical emergency often requires surgeons to undertake some one of the most challenging surgical or endovascular cases in medicine. This literature review aims to define and classify non‐A non‐B dissections, describe their epidemiology as well as their pathology. This review also aims to discuss the range of surgical techniques employed in their treatment and management and to investigate the patient outcomes associated with each technique.


| INTRODUCTION
Non-A non-B aortic dissections are a rare occurrence and treating this life-threatening medical emergency often requires surgeons to undertake some one of the most challenging surgical or endovascular cases in medicine. In general, acute aortic dissections are a serious condition characterized by a tear in the aorta's intima allowing blood to enter the medial layer of the aorta therefore splitting the aortic wall into two layers, hindering blood flow and causing end-organ malperfusion. 1,2 In 1994 von Segesser 3 proposed the term the non-A non-B dissection for dissections in which an intima tear is localized beyond the ascending aorta. In these forms, the dissection is limited to the aortic arch or can be described as a retrograde dissection arising from the descending aorta that extends into the arch and stops before the ascending aorta. 4 In untreated acute type A aortic dissection, the rate of mortality within in the first 48 h is greater than 50% and emergency open surgery is generally indicated. 5,6 However, the progression of acute type B dissection is often uncomplicated and the generally accepted first line treatment for this consists of medical therapy. 2,5,7 In complicated acute type B dissection, however, thoracic endovascular aortic repair (TEVAR) is the established treatment. 5,7 Non-A non-B dissections exist in between these two entities and represents only a fraction of the established literature on aortic dissections with evidence for their optimum treatment and management thin.

| CLASSIFICATION OF AORTIC DISSECTION
involving the descending aorta distal to the left subclavian artery ( Figure 1). 8,10 However, neither of these classifications address dissections involving the aortic arch alone or dissections comprising of the aortic arch and the descending aorta. When the dissection is limited to the aortic arch or can be described as a retrograde dissection arising from the descending aorta that extends into the arch and stops before the ascending aorta; these dissections are then termed as non-A non-B aortic dissections. 4,11 The Contemporary classifications such as the TEM (Type, Entry and Malperfusion) aortic dissection classification include non-A non-B dissections. 12

| EPIDEMIOLOGY
According to several studies, the incidence of non-A non-B aortic dissection is lower than type A aortic dissection but is higher than type B dissection. 8,13 The frequency of non-A non-B dissection among all acute aortic dissection patients has been shown to vary from 3% to 11% 4,10,12,13 (Table 1).
Studies by Sievers et al. 12 as well as Lempel et al. 13 showcased that non-A and non-B dissection patients tend to be younger and have a lower mortality compared to type A dissection patients. The median age for non-A non-B dissection patients was 59 years compared to 65 and 67 years for type A and type B dissection, respectively. 12 A study by Rylski et al. 10 divided non-A non-B dissection into descending-entry and arch-entry types with similar frequencies recorded in both types. 10 However, a prospective study by Urbanski et al. revealed a higher case load in descending-entry type patients.
This study also showed that surgery improved the outcomes of these patients compared to a more conservative approach. A multicentre study using the International Registry of Acute Aortic Dissection also reported that over 16% of type B aortic dissection cases had extension of the dissection into the aortic arch. 14

| PATHOPHYSIOLOGY OF NON-A NON-B DISSECTION
The wall of the aorta comprises three layers, the tunica intima, tunica media which largely is constituted of structural proteins including elastin and collagen and adventitia. 15,16 These layers form a thick aortic wall able to withstand high pulsatile pressure and shear stress.
Aortic Dissection is a condition characterized by the separation of these aortic layers. Classically it involves the breaching of the tunica intima, resulting in blood being diverted into a newly created channel within the medial layer of the aorta, known as the false lumen. A tear in the intimal layer tends to arise in locations where the rise in blood pressure is the greatest, commonly 2-2.5 cm above the aortic root. 16 The separation of these layers paves the way for the formation of a false lumen. Increase in size of the false lumen can lead to an aortic rupture which has a high mortality rate or a second intimal tear which allows blood to re-enter the intima to form a double-barreled aorta. 8 This tear can occur in any part of the aorta including the ascending, arch and descending aorta.  Other origins of an aortic dissection include an intramural hematoma and aortic ulceration. The former occurs due to the formation of a hematoma in the media, as a result of bleeding into the aortic wall from the vasa vasorum. 17,18 The latter, also referred to as a penetrating aortic ulcer and linked to atherosclerotic disease, is a penetration of the elastic lamina and can result in a hematoma forming in the tunica media. 19 Such hematomas can contribute to an aneurysm forming before aortic dissection.
The formation of an aortic aneurysm is thought to be more likely as a consequence of weakening of the tunica media, through the degeneration of collagen and elastin, which in turn increases higher wall stress. This is explained by Laplace's Law which states that 'wall stress is directly proportional to pressure (i.e., hypertension) and radius, and inversely proportional to vessel wall thickness. 20 Compromising the integrity of the aortic wall raises the risk of an aortic dissection. This is key to the risk factors associated with the condition.
Should an aortic dissection progress, through the passage of blood further down the false lumen of the tunica media, it has potential to stretch past the aorta and into the major blood vessels, Various surgical approaches exist, however, endovascular treatment has been shown in a recent systematic review and metaanalysis to be the most widely used technique. 11,25 In their study, TEVAR made up a significant percentage of surgical treatments for Non-A non-B dissections; TEVAR with extrathoracic surgical transposition of the supra aortic branches was adopted in 18% of surgeries and TEVAR with chimney stent graft in 36% of cases. 11 A growing proportion of studies also list TEVAR as the treatment of choice for acute complicated and many chronic type B and Non-A non-B aortic dissections. 25,26 Success of an endovascular approach for this subset of dissection patients is with some growing consensus attributed to the closure of the primary entry tear. 5 Application of different TEVAR zones is used to enable effective entry tear closure.
For descending entry patients that have an entry tear distal to the left subclavian artery, TEVAR Zone 3 (landing zone, i.e., distal to left subclavian artery) and TEVAR Zone 2 (landing zone, i.e., between the left subclavian and left common carotid) for more proximal entry tears just at the edge of the left subclavian artery. 10 Despite TEVARs more widespread use, an endovascular approach of this type might not always be feasible due to the lack of an adequate proximal landing zone as well as an increased risk of retrograde type A dissection which is particularly apparent in patients with additional aortic pathologies in Zones 1-3. 26 Application of TEVAR in patients with connective tissue diseases is also controversially reported in the literature. [26][27][28][29] Therefore, in a scenario in which an entry tear is located in the aortic arch, a more extensive arch repair such as a hybrid aortic repair involving rerouting of the supra-aortic arteries with TEVAR Zone 0 (landing zone at the ascending aorta) or even a complete arch replacement utilizing the frozen elephant technique (FET), could be necessary to close the primary entry tear. 28 5.1 | TEVAR

| TEVAR with chimney stent graft
This surgical approach has been shown to be reliable in cases where a suitable proximal landing zone can be established, where a simple left carotid to left subclavian bypass or one chimney stent graft for the left subclavian in sufficient. 11 When the aortic pathology involves or is in close proximity to the aortic branches, it is paramount that the endografts must cross their ostia to produce an adequate seal. 30 In this scenario, a standard angioplasty/stenting technique otherwise known as a chimney graft can make performing a TEVAR procedure possible using off the shelf devices. 31,32 This technique, first reported by Greenberg et al. 32  Covered stents were placed parallel to the aortic stent grafts to restore flow to the left common carotid artery while extending the proximal fixation zones; the left subclavian arteries were also intentionally covered after cerebrovascular assessment. All eight procedures were completed successfully with one main aortic stent graft deployed alongside one chimney graft implanted in the left common carotid artery. The authors report two retrograde type II endoleaks that were identified perioperatively but were left untreated but followed closely using computed tomography. 38 10 The cardiovascular risk profiles of these groups did not differ and the overwhelmingly majority of aortic segments were not dilated in patients from both groups. Across both groups the 30-day mortality rate was 9%, one patient suffered a stroke and two patients suffered a retrograde type A dissection. 10 Aortic repair due to new organ malperfusion, rapid aortic growth or persisting pain was performed in 43% of descending entry patients and 36% arch entry patients with a 0% in hospital mortality.
An earlier study by Lu et al. 41  complications and survival rates. 41 The authors reported surgery was successful in all patients except one with an operative complication and they report a 30-day mortality rate of 9%. 41 Thrombosis had formed in the aortic false lumen of the graft exclusion segment in all patients however the maximum diameter of this segment was shown to be decreased in 18 patients and stable in two. 41 Patency was observed at both mid-and long-term follow-up and no proximal endoleak, graft displacement or deaths were reported in this period.

| Hybrid aortic repair
When the entry tear occurs in the proximal aortic arch more invasive solutions can be necessary which include hybrid repair that involves rerouting of the arch branches and Zone 0 TEVAR or arch HOWARD ET AL.
| 1809 replacement. A recent systematic review and meta-analysis by Carino et al. 11 demonstrated that these hybrid techniques have been utilized for non-A non-B dissections in 21% of total surgical cases.
Zone 0 TEVAR use in hybrid procedures for acute dissection has been shown to be considered dangerous with a significantly higher risk of retrograde dissection in comparison to a more distal landing zone. [42][43][44] A 2020 study by Wang et al. 45  with Zone 2. The authors report a technical success rate of 100% and no incidences of paraplegia were reported. 47 Thirty-day mortality and incident of stroke were 0%. However, during the follow-up period (median follow-up of 12 months) a stroke and death occurred in one patient who was not associated with an endograft complication. During this follow-up period, overall mortality was 6.7% and the overall late endoleak rate was 7.7% however no retrograde dissection occurred across the cohort. 47 The authors also report no differences in outcome between acute and chronic dissection or proximal landing zones except for proximal endograft dimension. 47 An earlier paper published by Bünger et al. 48 48 Bünger et al. 48 concluded that hybrid repair in Zones 1 and 2 proved a viable alternative to conventional aortic arch surgery in these patients despite persistent issues with stroke and endoleak rate. Treatment of non-A non-B dissection patients with supra-aortic debranching and TEVAR in Zone 0, however, is associated with high mortality. 48

| Frozen elephant trunk
Another surgical treatment utilized in the surgical management of non-A non-B aortic dissection with proximal entry tear is the FET.
This procedure involves ascending aorta and arch replacement in combination with antegrade stent graft implantation in the descending thoracic aorta while using a single hybrid prosthesis. 26 A recent systematic review and meta-analysis by Carino et al. 11 found that 7% of patients were treated with this technique and that FET may also be an important option in cases of malperfusion syndrome as it can potentially open the compressed true lumen and cover any additional entry tears that could be positioned in the proximal descending aorta so that pressurization the false lumen is maintained. 11,26,49 FET is also recognized in the literature to promote favorable remodeling in the distal aorta. 50,51 Another advantage of FET is no type I endoleak as well as its ability to establish a highly stable proximal landing zone for the eventual stent graft implantation in the descending thoracic aorta. 50,52,53 However, the main limitation associated with FET is the increased surgical trauma secondary to the necessarily prolonged periods of extracorporeal circulation, circulatory arrest as well as myocardial ischemia. 11 In addition, the technical demand of this procedure requires experienced surgeons in high volume aortic centers. 26 A 2020 study by Kreibich et al. 54 54 The authors report one patient death during follow-up after 2 years (not aorta related) and 16 patients subsequently underwent an aortic reintervention after 7.7 months. 54 Kreibich et al. 54 concluded that FET is an effective treatment option for acute complicated and chronic type B as well as non-A non-B aortic dissection patients in whom primary endovascular was not deemed as feasible.
They also conclude that this study underlines the considerable need for aortic reinterventions and the importance of continuous followup of patient after undergoing FET procedures.
An earlier study by Zhao et al. 55  The in-hospital mortality rate was recorded at 4.1% with one patient dying of multiorgan failure after surgery. 55 No incidences of paraplegia were reported. 55 During follow-up one patient was reported to have died following gastrointestinal bleeding 2 months after surgery and type II endoleak occurred in one patient. The 5-year survival rate was 91.7%. 55 The authors concluded that the applica-  4 In the conservatively treated patient group, three patients had died by 28 months of follow-up, one from an aortic rupture and two due to the progression of the dissection and subsequent malperfusion. 4 The authors concluded that surgical treatment of acute aortic dissection involving the arch but sparing the ascending aorta seemed to offer improved clinical outcomes. 4

| Medical replacement
When considering a suspect aortic dissection, it is important to provide haemodynamic support. While this resuscitation protocol may vary locally, medications such as noradrenaline and dobutamine, often administered intravenously, have been indicated in the treatment of aortic dissections. 57 Carino et al. 11 includes studies focusing on medical treatment of non-A non-B dissections which show admission to intensive care units for monitoring of blood pressure, analgesia and antihypertensive therapy to be indicated as a method of medical treatment. 11 Their analysis showed that the proportion of medically treated patients ranged from 5% to 54% of patients. 11 The 30-day mortality rate for these patients was recorded as 14% in comparison to 3.6% in patients who had undergone intervention. 11 6 | CONCLUSIONS