Abstract
Background: Acute type B aortic dissection (TBAD) is a rare condition
that can be divided into complicated (CoTBAD) and uncomplicated
(UnCoTBAD) based on certain presenting clinical and radiological
features, with UnCoTBAD constituting the majority of TBAD cases. The
classification of TBAD directly affects the treatment pathway taken,
however, there remains confusion as to exactly what differentiates
complicated from uncomplicated TBAD.
Aims: The scope of this review is to delineate the literature defining
the intervention parameters for UnCoTBAD.
Methods: A comprehensive literature search was conducted using multiple
electronic databases including PubMed, Scopus, and EMBASE to collate and
summarize all research evidence on intervention parameters and protocols
for UnCoTBAD.
Results: A TBAD without evidence of malperfusion or rupture might be
classified as uncomplicated but there remains a subgroup who might
exhibit high-risk features. Two clinical features representative of
“high risk” are refractory pain and persistent hypertension. First
line treatment for CoTBAD is TEVAR, and whilst this has also proven its
safety and effectiveness in UnCoTBAD, it is still being managed
conservatively. However, TBAD is a dynamic pathology and a significant
proportion of UnCoTBADs can progress to become complicated, thus
necessitating more complex intervention. While the “high risk”
UnCoTBAD do benefit the most from TEVAR, yet, the defining parameters
are still debatable as this benefit can be extended to a wider UnCoTBAD
population.
Conclusion: Uncomplicated TBAD remains a misnomer as it is frequently
representative of a complex ongoing disease process requiring very close
monitoring in a critical care setting. A clear diagnostic pathway may
improve decision making following a diagnosis of UnCoTBAD. Choice of
treatment still predominantly depends on when an equilibrium might be
reached where the risks of TEVAR outweigh the natural history of the
dissection in both the short- and long-term.
Keywords: Type B aortic dissection, TBAD, complicated, uncomplicated,
TEVAR
Introduction
Acute type B aortic dissection (TBAD) is a rare disease with minimal
data on the incidence in the United Kingdom. However, there is evidence
an annual incidence of 550 might be expected for a population of 55
million [1]. It has been subdivided into complicated (CoTBAD) and
uncomplicated (UnCoTBAD) depending upon certain presenting clinical
features. Interestingly, it is unknown how many TBAD patients initially
present as uncomplicated as the disease process may be evolving with
clinical and radiological characteristics changing rapidly at times.
However, data suggests, up to 75% of TBAD are initially classified as
uncomplicated [2]. This is an important issue because once
classification has been determined then the optimum treatment plan can
be instigated. In the case of CoTBAD, this means that, as well as
continuing optimal medical therapy (OMT), an endovascular option should
also be considered if the aortic arch anatomy is suitable. However,
there remains confusion as to exactly what differentiates complicated
from uncomplicated TBAD as very often subtle differences in
interpretation of clinical and radiological findings may lead to
significant differences in treatment plans. The scope of this review is
to delineate the literature defining the intervention parameters for
UnCoTBAD.
Uncomplicated type B aortic dissection: Is it a misnomer?
In an attempt to redefine nomenclature associated with TBAD, the Society
for Vascular Surgery/Society of Thoracic Surgeons (SVS/STS) produced an
up-to-date document in 2020. Complicated and uncomplicated TBAD were
defined, as well as high risk features for aortic dissection [3]. An
UnCoTBAD was defined as no evidence of rupture or end-organ malperfusion
with no associated high-risk features. However, strict definitions for a
diagnosis of malperfusion are not wholly established in the literature,
and concerns have been raised whether this should be a clinical
diagnosis or whether additional imaging is required for diagnosis
[4]. Furthermore, radiographic but not clinically apparent
malperfusion may be indicative of a poor clinical outcome. Importantly,
this “radiographic malperfusion” of the renal or mesenteric beds is a
vague finding that may be related to the CT angiography (CTA) phasing
and should be interpreted with some caution. It is important to realise
a rise in creatinine post TBAD is not necessarily indicative of renal
malperfusion.
A TBAD without evidence of malperfusion or rupture might be classified
as uncomplicated but there remains a subgroup who might exhibit
high-risk features. Two clinical features representative of “high
risk” are refractory pain and persistent hypertension. Both are common
in the acute presentation of a TBAD and data from the International
Registry of Acute Aortic Dissection (IRAD) indicates almost all TBAD
patients present with pain and >70% of that will be
located in the chest [5]. Ongoing pain despite adequate opiate
analgesia puts a patient in a high-risk category, whilst hypertension
despite three different antihypertensives is defined as refractory.
Again, in the absence of rupture and malperfusion this situation is
classified as a “high risk” aortic dissection.
The “high risk” radiographic findings which have been associated with
the risk of developing late aortic complications include
>40mm maximal thoracic aortic diameter, a primary entry
tear of >10mm, location on the inner curve of the aortic
arch and a false lumen (FL) diameter >22mm [6,7].
Furthermore, there are other findings not included in the current
criteria for high-risk TBAD, such as the location of entry tear at the
concavity of the distal aortic arch in CoTBAD compared to an UnCoTBAD
[8,9].
At least 25% of those initially diagnosed as UnCoTBAD may ultimately
progress to CoTBAD [10,11]. In addition, there may be a delay of up
to 14 days before an initial diagnosis of UnCoTBAD becomes complicated
[11]. Despite this, there is evidence that up to 40% of those
diagnosed and remaining UnCoTBAD develop aneurysmal dilatation of the
thoracic aorta at a mean of 18 months later [12,13]. In this
situation, it may be beneficial to develop an early “high risk” change
in order that thoracic endovascular aortic repair (TEVAR) is more likely
to be performed so that the consequences of late aortic dilatation and
rupture might be reduced.
This may have significant consequences as the categorisation of a TBAD
to a specific group early on can radically change the treatment plan
followed. This might be to the long-term detriment of the patient. One
thing which is apparent is that a TBAD is an evolving process and a
seemingly straightforward UnCoTBAD can become complicated within a few
days. This illustrates the importance of regular observation for
clinical change and also a protocol in place for serial imaging to be
performed.
The dilemma of TEVAR or OMT in UnCoTBAD
The aim of TEVAR is to seal off the proximal entry tear in the upper
thoracic aorta, which is then extended distally, usually to the origin
of the coeliac axis. This is done to cover any re-entry tears and to
reduce FL pressurisation. However, the risk of spinal cord ischaemia can
be an unintended consequence, thus serious consideration must be made to
revascularise the left subclavian artery (if covered) and the placement
of a spinal drain. Once TBAD has progressed to the chronic stage, TEVAR
may no longer be a viable option and either open repair or a branched or
fenestrated endovascular option should be considered [14]. What is
apparent is that those diagnosed as CoTBAD cannot become an UnCoTBAD
because the time until treatment equipoise for TEVAR and OMT or OMT
alone for UnCoTBAD is uncertain [15]. The many different
radiological and clinical features that emerge early on in the disease
process may contribute to this uncertainty.
The optimum treatment for UnCoTBAD is still unknown, especially since
the addition of “high risk” features to be considered has led to a
more aggressive plan being implemented. It is important to realise the
reason for intervention in acute TBAD is to treat the long-term
consequences of a pressurised FL. There is evidence that remodelling is
most effective in the subacute phase (15-30 days), and if a TBAD is
considered for intervention, then it should be performed within the
initial 90 days since symptom onset [16,17]. Jubouri et al. [18]
recently highlighted the evidence in the literature on the mid- and
long-term clinical outcomes of TEVAR in UnCoTBAD, demonstrating its
superiority to OMT.
Two prospective randomised trials on UnCoTBAD and TEVAR have been
carried out. Both have been criticised for a variety of reasons,
including small sample size, lack of long-term follow-up, varying times
for stent insertion after the initiating event, and industry led
research. The INSTEAD (INvestigation of Stent Grafts in Aortic
Dissection) trial randomised 140 chronic UnCoTBAD patients into two
groups [19]. The first group was OMT and TEVAR whilst the second
group was OMT alone with the primary outcome measure being 2-year
mortality rates. Aorta-related deaths, disease progression, and aortic
remodelling were all secondary outcomes. Any TEVAR was performed within
2 to 52 weeks with the majority being performed within 10 to 12 weeks.
It is worth noting that there was no difference in mortality rates,
however, the TEVAR group showed significantly improved aortic
remodelling compared to the OMT group (91.3% and 19.4%,
p<0.001). The principal conclusion, however, was that, despite
the radiologically improved remodelling, TEVAR provided no considerable
advantage over OMT. It should also be noted that the UnCoTBAD patients
in this study always reached the subacute stage without any
complications developing.
This study was extended to include a 5-year follow up to become the
INSTEAD-XL study. Thoracic stent grafting reduced all-cause mortality
(11.1% v 19.3%; p=0.13), aorta related mortality (6.9% v 19.3%; p=
0.04) and progression of dissection (27% v 46.1%; p=0.04) relative to
OMT alone [20]. Also, complete FL thrombosis was observed in 90.6%
of TEVAR group compared to 22% in OMT group. Overall, TEVAR conferred a
long-term survival advantage which manifested itself between 2-5 years
following the TBAD. Hence, the conclusion was pre-emptive TEVAR in
stable patients with an UnCoTBAD should be considered to improve
long-term outcomes [20].
The Acute Dissection Stent Grafting or Best Medical Treatment (ADSORB)
trial compared OMT to OMT and TEVAR for uncomplicated TBAD [21].
This study specifically examined post intervention aortic morphology
with the primary endpoints being FL thrombosis, aortic dilatation and
rupture. No deaths occurred in either group within the first 30 days,
however, due to disease progression there were three cross overs from
the OMT group to TEVAR plus OMT one. After 12 months of surveillance, FL
thrombosis did not occur in 97% of OMT patients compared to 57% of the
group undergoing TEVAR with OMT. Further evidence showed a maximum FL
diameter decrease of 7mm in the TEVAR + OMT group compared to an
increase of 4.3mm in the OMT only group. The conclusion was that TEVAR
can be safely and effectively used to treat UnCoTBAD [22].
TBAD population risk analysis
The holy grail for the management of UnCoTBAD is to reliably identify
those subgroups of patients who are at high risk for aorta-related
complications without immediate risk of rupture or malperfusion. Three
principal factors have been proposed; an initial aortic diameter of
>40mm, an entry tear >10mm and a free-floating
TL (this occurs when the entire circumference of the aorta has
dissected) [23]. Song et al. [24] showed that the upper
descending thoracic aorta is the principal site where aneurysmal
dilatation occurs following a TBAD. He also identified a diameter of
22mm of the FL at presentation as a powerful predictor of late
aneurysmal change of the thoracic aorta. It was also considered a more
accurate predictor for long term complications than the initial overall
thoracic aortic diameter. A positive correlation was also identified
between the number of proximal entry tears and future thoracic aortic
dilatation. A single-entry tear was associated with a higher growth rate
of the thoracic aorta [25,26]. This was supported by Ray et al.
[27] who published data on UnCoTBAD presenting within 2 weeks of the
initial event where the most sensitive indicator for mortality was an
aortic diameter >44mm with a FL diameter of
>22mm.
Accurate assessment at the time of acute presentation allows TBAD
patients to be classified as complicated or uncomplicated. Regular
clinical assessments need to be done as well as routine blood tests
looking for biochemical markers of hepatic, gut or renal ischaemia.
Lower limb weakness may be due to spinal cord vascular compromise or
true lumen compression by the FL indicating arterial insufficiency. Due
to development of rupture or malperfusion, the UnCoTBAD group may remain
uncomplicated or be diagnosed as delayed complicated. Other “high
risk” symptoms and signs to evaluate include a primary entry tear
>10mm located on the arch concavity, total aortic diameter
>40mm and an associated FL diameter of >22mm.
Those who have intractable hypertension or ongoing pain following
presentation may also benefit from early TEVAR [17,28]. It raises
the question on whether these patients should be classified as CoTBAD
despite no evidence of rupture or malperfusion. According to the IRAD
registry, there is evidence that the presence of hypertension or
refractory pain in a UnCoTBAD is associated with an increased mortality
rate [29].
Conclusion
Uncomplicated TBAD remains a misnomer as it is frequently representative
of a complex ongoing disease process requiring very close monitoring in
a critical care setting. A clear diagnostic pathway may improve decision
making following a diagnosis of UnCoTBAD. In the absence of rupture or
malperfusion (both clinically and on imaging) a diagnosis of UnCoTBAD
can be made. This may then proceed in one of two ways depending on the
appearance of rupture or malperfusion and whether high risk features
appear on subsequent scans (usually a few days apart). If there is no
evidence of the aforementioned then the same initial diagnosis remains.
Choice of treatment is very much directed by when equipoise might be
reached where the risks of TEVAR outweigh the natural history of the
dissection in both the short- and long-term.