4. Discussion
The FET technique has become a consolidated choice for TAR in patients
with diffuse aortic pathologies. This is due to its highly favorable
results which can be considered superior to conventional arch repair. To
elaborate, the FET procedure offers improved aortic remodeling, splendid clinical outcomes, shorter procedure-related times, and a more ideal proximal landing zone for further endovascular
completion if necessary [25, 57, 58]. Although providing all those abovementioned benefits, it still comes with a non-negligible risk of
negative remodeling, dSINE, and endoleak, which may require secondary
intervention, negating its one-step advantage. Yet, the choice of FET
device type can greatly influence results [59].
Aortic remodeling, which is well-established in the literature as a
valuable prognostic tool for patients undergoing surgical repair of
TAAD, is outlined as positive, stable, or negative based on the aortic
lumen (AL) and TL diameter changes as well as the extent of false lumen
thrombosis (FLT) [58, 60]. According to Dohle et al. [61], and
based on the Society of Vascular Surgery standards [62], remodeling
is considered positive when there is a ≥10% expansion in TL diameter
and/or a reduction in overall AL diameter. Meanwhile, an increase in the
size of the FL/AL is classed as negative remodeling. As expected,
without significant changes in aortic diameters the remodeling process
is regarded as stable [61, 62]. In TAAD, the constant FL antegrade
perfusion caused by the intimal entry tears gives rise to aneurysmal
deteriorations along the aorta; however, if these entry points remain
patent after surgical repair, this presents an important risk factor for
aortic dilatation and rupture as well as an increase in the need for
further distal reintervention [9, 63]. Additionally, FL expansion
has been shown to be associated with the entry's size and location [64]. For example, Turley et al. [65] demonstrated that
the presence of major vessels originating from the FL could play a
crucial role in the disruption of the FLT process. Occlusion of the FL
entries, on the other hand, hampers the antegrade blood flow through the
FL which promotes FLT, leading to TL re-expansion and favoring improved
distal perfusion [66, 67]. Thus, utilizing longer FET stent grafts aids aortic remodeling through extended coverage of the aorta distally,
obliterating any entry tears and stabilizing the diseased intima
[9].
Although the exact mechanisms behind the process of aortic remodeling
remain unclear, the FET procedure drives excellent aortic remodeling.
This is evident in a meta-analysis evaluating 1279 patients with TAAD
undergoing TAR with FET where the rate of FLT was found to be 96.8%
around the stent graft (or at the DTA level) [68]. Interestingly,
the varying extent of remodeling along the aorta (i.e., the stent-graft,
DTA, and AA levels) is well-documented in the literature. This was
demonstrated by Dohle et al. [69], where after 1 year of follow-up,
volumetric calculations found remodeling was 98% at the stent-graft
site, 68% from the end of the stent-graft to the coeliac trunk level,
and 39% from the coeliac trunk to the aortic bifurcation level. Also,
positive (or stable) aortic remodeling rates followed the same descending trend,
marking 94%, 64%, and 54% at each respective level. The authors also
found a significant increase in the volume of the thrombosed FL after the first year of follow-up, distal to the stent graft. Iafrancesco and his colleagues [58] suggested that the FLT rate influences the AL diameter changes. Here, 99.3% FLT was recorded at the level of
mid-DTA compared to 13.9% achieved at the distal AA, confirming
our earlier statement on the varying FLT rates along the length of the
aorta, with remodeling decreasing more distally [58]. Importantly,
our results clearly show an utterly congruent trend as the rate of FLT
around the stent graft was 91%, with 61% at the thoracic aorta and
36% at the level of the AA.
As aforementioned, several FET devices are available commercially, the most commonly used being Thoraflex Hybrid, E-Vita, J Graft Frozenix, and Cronus, in this order. However, evidence in the literature
supports Thoraflex Hybrid’s superiority in clinical outcomes over its
competitors. This is no different when it comes to aortic remodeling, as
Thoraflex Hybrid has been proven to promote excellent FLT and is
associated with significant positive changes in aortic diameters [9,
10, 59]. This is evident in multiple studies, one of which is Mehanna et al. [37] which featured Spearman rank correlation tests
to assess the correlation of their results. This testing revealed that
aortic remodeling ratios, before and following the procedure, had a
moderately positive correlation. The study reported a significant
expansion of the TL ratio using Thoraflex Hybrid post-operatively, with
a median increase from 0.31 to 0.4 mm (P = 0.042), as well as a
significant FL ratio decrease from 0.66 to 0.54 mm (P = 0.02). The
authors also described the unique interrupted pattern of Thoraflex
Hybrid stent-graft, which is thought to protect the aortic wall from the
substantial forces of blood flow to help achieve excellent aortic
remodeling. Overall, it was concluded that the Thoraflex Hybrid is the
safest and most efficacious FET device, promoting superior aortic
remodeling [37]. Interestingly, a Thoraflex Hybrid study by Usai et
al. [70] used volume measurements to assess aortic diameters instead
of the computed tomography scanning used in most studies, allowing more
accurate measurements to be taken. Similar to Mehanna [37], Usai
[70] also found that the Thoraflex Hybrid induced substantial
expansion of the TL along with shrinkage and thrombosis of the FL. Prior
to the procedure, the mean TL volume was 77.03 cm3 (±
47.96 cm3); this increased to 133.84
cm3 at 24 months of follow-up. The long-term analysis of
TL volumetric expansion evidenced a statistically significant growth
even 2 years after the FET procedure (P = 0.047). Another aspect showing
Thoraflex Hybrid’s superiority over other FET HPs is its outstanding
ability to promote aortic remodeling distally, as Usai et al. [70]
also noted that the most significant growth in the surface TL
measurement was at the level of the diaphragm (P = 0.00193). In
addition, the results in Fiorentino et al. [51] confirmed that the
Thoraflex Hybrid yields TL expansion not only at the level of pulmonary
bifurcation (FLT rate = 73.1%) but also at the distal DTA as well as
the AA. Furthermore, upon searching the literature, the need for
endoprosthetic extensions due to incomplete FLT was found to be less by
6% with the Thoraflex Hybrid in comparison with the E-Vita HP, its main
market competitor [71]. To further prove Thoraflex Hybrid’s superior
efficacy, Shrestha et al. [72] reported a 100% FLT rate among 100
patients in their single-center study. On the other hand, Akbulut et al.
[73] observed a 93.9% and 54.5% FLT rate at the pulmonary trunk
and diaphragmatic levels, respectively, using the E-Vita graft.
Unfortunately, the use of Frozenix and Cronus FET grafts is
geographically confined to only a few countries, thus data on their
aortic remodeling performance is limited and would be unreliable for
comparisons [9].
Developing SINE is one of the main drawbacks of the FET technique, in which the false lumen patency negatively impacts aortic remodeling by increasing thoracic aorta diameter and thus, increases the need for reintervention [4, 9,
69]. Kreibich et al. reported a significant negative
correlation between the TL diameters at the level of the stent graft and the development of dSINE [74]. SINE can develop at any point during
follow-up post-FET, and its onset is usually asymptomatic but can
progress rapidly [74, 75]. SINE occurs when the stent-graft portion
of the FET device induces injury to the intima of the aorta due to the
pathological dissection membranes mismatching with the stiffer stent
[9]. In addition, evidence in the literature shows that the incidence
of dSINE in patients with chronic dissection undergoing FET is higher
than in acute patients, which can be attributed to the more advanced
fibrotic changes in the chronic dissection membrane [75]. In this regard, Janosi found that AD patients with a longer time interval between diagnosis and intervention were more prone to developing dSINE [75].
Upon searching the literature, the incidence of dSINE following FET was
found to be highly variable, ranging from 0-27.3% [50, 74, 76-78].
The abovementioned wide range of incidence described in the literature could be attributed to the differences among stent types, sizes, and the hybrid prosthesis loading process, as well as the patient anatomical/clinical characteristics, and study design. Evidence in the
literature suggests that severe graft oversizing as well as using shorter
graft lengths are the main contributing causes for dSINE, in addition to
adopting a more proximal landing/implantation zone to deploy the stent graft (e.g. zone 2) [9, 10, 59]. Our results showed a pooled
estimate of 2% for dSINE after FET with a high heterogeneity which
disappeared amongst cases registered by European centers. If left
untreated, dSINE can lead to a mortality rate of up to 25%, hence it
requires prompt distal reintervention to prevent further FL enlargement
or rupture [9, 74]. Importantly, secondary TEVAR intervention can
achieve excellent results in this clinical scenario [7, 36].
Moreover, several studies have supported the superiority of TEVAR over
open surgical re-intervention, particularly when it comes to mortality
and complications [32, 79]. Furthermore, Loschi et al. [41]
compared TEVAR reintervention to open surgical reintervention following
FET and demonstrated a significantly higher clinical success rate at five
years (95% vs 68%, P = 0.022) as well as significantly fewer
complications (5% vs 42.9%, P = 0.004) amongst the TEVAR
reintervention group. Despite the excellent clinical success for
secondary TEVAR after FET, it should only be utilized with caution in
patients with connective tissue disorders owing to disputable results
reported in the literature [32].
Thoraflex Hybrid’s superiority extends to dSINE by demonstrating
outstandingly low incidence compared to the other devices. Upon
searching the literature, the incidence of dSINE reported in the studies
identified ranged from 0-14.5% with Thoraflex Hybrid, 1-18.2% with
E-Vita, and 0-27.3% with Frozenix [9,10, 59]. Charchyan et al.
[80] compared dSINE incidence with ring-shaped nitinol stent-graft
(Thoraflex Hybrid) against Z-shaped nitinol stent-grafts (E-Vita) and
distal dissection-specific stent-grafts (Valiant retrograde stent-graft,
Medtronic Vascular, Santa Rosa, CA, USA). The results prove that dSINE
occurrence is significantly lower with Thoraflex Hybrid than with E-Vita
(4.5% vs. 13%, P = 0.043). Another study directly comparing both these
grafts is Berger et al. [77], which concluded that Thoraflex Hybrid
yields more favorable results. Here, 14.5% of patients in the Thoraflex
Hybrid developed dSINE post-FET relative to 18.2% with E-Vita Open (P =
0.19). The Frozenix HP, however, was found to be associated with the
highest incidence of dSINE whilst, on the other hand, no dSINE data was
identified for Cronus due to its geographical confinement leading to a paucity of data [9, 81]. Lastly, Thoraflex Hybrid's unique circular
design and special material have been shown to reduce the stress on the aortic wall, contributing to the excellent dSINE results seen across the literature and in our study [9, 10, 82].
Endoleak after FET has been described across the literature as an
unsatisfactory seal at the stent-graft anastomosis site either at its
proximal or distal end which usually necessitates secondary
intervention. In a study evaluating 107 patients who underwent TAR with
FET endoleak was the second main indication for reintervention [5].
The incidence of this treatable FET complication has been reported to be
ranging from 11% to 35%. Importantly, untreated endoleak negatively
influences the aortic remodeling process by contributing to constant AL
expansion. Therefore, the FET stent-graft size and length must be
selected carefully after accurate measurement [9, 10, 46, 81].
Kandola et al. [46] noted that 77% of patients with endoleak or sac
expansion had < 10% of distal stent oversizing whilst the
remaining 23% had less than 30 mm distal seal in the healthy portion of
the aorta despite adequate oversizing. Stents of appropriate oversizing
and sealing were significantly more commonly deployed in patients with
no endoleak or sac expansion (P = 0.0031) [46]. In the present
review, the pooled estimate of endoleak was calculated as 3% with a
high heterogeneity which disappeared among patients receiving Thoraflex
Hybrid in European centers. The study by Berger et al.
[77] reported 0% endoleak incidence in the Thoraflex Hybrid group
of patients whilst 3% of patients receiving the E-Vita HP developed
endoleak. Another study reporting a 0% incidence of endoleak is the
aforementioned Chu et al. [52]. On the contrary, Tsagakis et al.
[83] found that 4.6% of patients experienced endoleak with the
E-Vita device. To further demonstrate Thoraflex Hybrid’s outstanding
efficacy, Tan et al. [10] analyzed data from 931 patients who
underwent FET using Thoraflex Hybrid and reported only 1 (0.1%) case of
endoleak over a follow-up period of 84 months. In addition, the authors
stated that the proximal sewn graft of Thoraflex Hybrid, combined with
its distal anastomosis cuff, eliminate the risk of endoleak. Overall,
the freedom from adverse events at 84 months after Thoraflex Hybrid
implantation was 94%. All the above evidence show beyond doubt that the
Thoraflex Hybrid is the best aortic arch prosthesis on the global
market.
There is a clear trend within the literature associating the incidence
of dSINE and endoleak with aortic remodeling. In addition, FET graft
size and length have been strongly linked to these outcomes. This topic
has been discussed in detail by Jubouri et al. [9] and Kayali et al.
[81]. Research evidence has demonstrated that severe graft
oversizing increases the likelihood of dSINE occurring which, in turn,
negatively affects aortic remodeling, while at the same time
independently causing negative remodeling [9, 10, 59]. On the other
hand, stent graft undersizing may cause endoleak, which also hinders the
remodeling process. Therefore, graft oversizing by 10-15% is
recommended [75, 84, 85]. However, the optimal graft length remains
debatable as longer grafts have been shown to promote improved
remodeling and lower dSINE occurrence while increase the risk of SCI
[9]. In this sense, Ma et al. [82] recommend using tapered stent grafts in order for them to be harmonious with the tapering nature
of the descending aorta, thus preventing size mismatch and,
consequently, dSINE, endoleak and negative remodeling. The Thoraflex
Hybrid is a highly versatile and unique device as it is the only FET HP
offering a wide range of proximal and distal stent-graft diameters as
well as multiple device lengths which clearly explains its superior
results achieved [9, 10, 59, 82].