Abstract
Background: There is emerging evidence to support pre-emptive
thoracic endovascular aortic repair (TEVAR) intervention for
uncomplicated type B aortic dissection (unTBAD). Pre-emptive
intervention would be particularly beneficial in patients that have a
higher baseline risk of progressing to complicated TBAD (coTBAD). There
remains debate on the optimal clinical, laboratory, morphological and
radiological parameters which would identify the highest-risk patients
that would benefit most from pre-emptive TEVAR.
Aim: This review summarises evidence on the clinical,
laboratory, and morphological parameters that increase the risk profiles
of unTBAD patients.
Methods: A comprehensive literature search was carried out on
multiple electronic databases including PubMed, EMBASE, Ovid and Scopus
in order to collate all research evidence on the the clinical,
laboratory, and morphological parameters that increase the risk profiles
of unTBAD patients
Results: At present, there are no clear clinical guidelines
using risk-stratification to inform the selection of unTBAD patients for
TEVAR. However, there are noticeable literature trends that can assist
with the identification of the most at-risk unTBAD patients. Patients
are at particular risk when they have refractory pain and/or
hypertension, elevated C-reactive protein (CRP), larger aortic diameter
and larger entry tears. These risks should be considered alongside
factors that increase the procedural risk of TEVAR to create a
well-balanced approach. Advances in biomarkers and imaging are likely to
identify more pertinent parameters in future to optimise the development
of balanced, risk-stratified treatment protocols.
Conclusion: There are a variety of risk profiling parameters
that can be used to identify the high-risk unTBAD patient, with novel
biomarkers and imaging parameter emerging. Longer-term evidence
verifying these parameters would be ideal. Further randomized controlled
trials and multicentre registry analyses are also warranted to guide
risk-stratified selection protocols.
Keywords: Type B Aortic Dissection, Aortic Dissection, Aneurysm, Aortic
Surgery
Introduction
Uncomplicated type B aortic dissection (unTBAD) is estimated to
constitute 75% of type B aortic dissection (TBAD) cases, with up to
50% of those progressing to become complicated. Despite this, and even
though thoracic endovascular aortic repair (TEVAR) has proven its safety
and effectiveness in the treatment on unTBAD, it is still being managed
conservatively with optimal medical therapy (OMT). However, with the
surge of emerging evidence in the literature supporting the use of
pre-emptive TEVAR in unTBAD, the paradigm of clinical practice is
shifting (1). Yet, there seems to be a strong debate on the optimal
clinical, laboratory, morphological and radiological parameters defining
the intervention threshold in clinical guidelines.
This review will discuss current literature pertaining to the risk
factors in unTBAD patients undergoing TEVAR, with a focus on clinical,
laboratory and morphological/radiographic features that increase the
risk profiles of unTBAD patients. In the absence of clear clinical
guidelines, a stratification scheme to identify and managed more
vulnerable acute unTBAD patients with TEVAR is presented which could be
executed using the risk factors identified in this review.
Clinical parameters
One of the most important clinical parameters to control in unTBAD is
the heart rate, as when this exceeds 60 bpm in unTBAD patients it could
lead to poorer long-term outcomes. Kodama et. al (2) observed lower
rates of aortic events in OMT managed unTBAD patients with heart rate
controlled at < 60 bpm (OR 0.25, p = 0.0059) (2). Surgical
intervention was also lower at < 60 bpm versus >
60 bpm (0% versus 18.7%, P = 0.005) (2). The patient’s perception of
pain also warrants caution. It is imperative to be vigilant of rarer
absences of chest pain on admission, as this has been significantly
associated with increased in-hospital mortality (OR 3.49, p = 0.01) (3).
Even after OMT management, recurrent and/or refractory pain or
refractory hypertension must be carefully observed. These parameters
appear to elevate the risk of in-hospital mortality (17.4% versus 4%,
p = 0.0003), and multivariate analysis showed are significant predictors
of in-hospital mortality (OR 3.31, 95% CI 1.04 - 10.45, p = 0.041) (3).
Laboratory parameters
Certain blood tests are likely to have predictive and non-predictive
values for aortic enlargement, and these will only be confirmed in
studies that feature longer-term follow-ups. C-Reactive Protein (CRP)
elevation is common in patients with TBAD and usually peaks between days
3-6 after the index event. Peak CRP, which needs to be obtained more
than for reliable risk assessment (4), has been strongly linked to
long-term adverse events in patients with unTBAD and could therefore be
used as a prognostic marker. In a comparative study, a mean CRP levels
of 12.0 mg/dL (with a lower limit of 9.61 mg/dL) and 19.5 mg/dL (with a
lower limit of 14.90 mg/dL) were shown to be strong predictors of
adverse events (HR 3.25, p = 0.01) (HR 6.02, p = 0.0001). This has been
corroborated by others who demonstrate that CRP levels >
15.0 mg/dL may independently predict aortic events (OR 4.199, 95% CI
0.76 - 23.19, p = 0.1) (5). Peak CRP has been identified as a
significant predictor of lower PaO2/FiO2 ratio which usually
necessitates mechanical ventilation and is associated with further
complications (6). However, as CRP is a non-specific marker, its utility
in predicting the extent of aortic dissection may be limited by
confounding inflammatory processes.
Fibrin degradation products (FDPs) may also be of prognostic value and
appear to share a relationship with the patency and thrombotic status of
the false lumen (FL) (7). The status of the FL is a known mortality
determinant (8). Tsai et. al (8) previously found ± 3-year mean (± SD)
mortality rates to be greatest in patients with partial FL thrombosis
(31.6 ± 12.4 %) than those with patent (13.7 ± 7.1 %) or completely
thrombosed FL (22.6 ± 22.6 %, p = 0.003). Nagaoka et. al (7) then found
that FDP levels were significantly higher in patients with partial FL
thrombosis (35.8 ± 43.2, median 18.8 μg/mL) versus those with patent or
completely thrombosed FL (14.0 ± 21.3, median 5.5 μg/mL, p = 0.01). FDP
may predict 1-year aortic events when admission levels are ≥ 20 μg/mL
(OR 7.8, 95% CI 1.4 - 43.3), and can further assist radiological
findings in the recognition of FL partial thrombosis (5, 7). Aortic
enlargement, however, was not associated with platelet count, D-dimer,
and thrombin-antithrombin III complex (5). The follow-up interval in
this study (5) was only 1 year and therefore long-term significance
remains elusive. FDP is also not easily measured in emergency settings
and may therefore be less accessible for some institutions.
Troponin could be also used as a laboratory parameter in unTBAD by
approximating the extent of ischaemic myocardial injury.
Demand-ischaemia can occur due to blood pressure fluctuations, aortic
regurgitation or an intimal flap covering the coronary ostia. Elevated
troponin levels have been shown to be significantly associated with a
higher risk for short-term mortality (OR 2.57, 95% CI 1.66 - 3.96) (9).
Morphological and radiologic parameters
Anatomic risk-stratification is currently the mainstay of TBAD
assessment. Many morphological features have been noted that may lead to
further aortic degeneration and secondary emergencies, including aortic
morphology and diameter (10-14), position and size of entry tear (15,
16), and FL diameter and patency (12-14, 17, 18).
Aortic diameter
Aortic diameter has been reported as the most sensitive independent risk
factor (HR 8.6, p < 0.01) for mortality in unTBAD (19).
Strikingly, intervention rates at 1-, 5-, and 10- years in patients with
an aortic diameter > 44mm were 18.8%, 29.5% and 50.3%
versus 4.8%, 13.3% and 13.3% in those < 44mm (p <
0.01). Overall survival is illustrated in Figure 1 (19). Others
have also described aortic diameter > 40 mm as predictor
for late aortic events (HR 3.18, 95% CI 2.12 to 5.05, p <
0.001) (12) and > 40 mm is generally regarded as the
cut-off for predicting late aortic intervention (15, 20).
The morphology of aortic diameter is also dictated by interplaying
pressure relationships between the TL and FL. Clearly demarcated
circular FL configurations are more highly pressurised due to their
blood volumes. The fragility of the vessel wall in these “fusiform”-
shaped aortas likely contributes to dilatation (12). Some have suggested
that a circular FL may cause an elliptic TL configuration that has been
associated with adverse aortic growth based on results from a
conservatively managed cohort (n = 62) (21). Similarly, Song et. al (22)
found increased FL: total aortic diameter ratios in the proximal and
descending thoracic aortas of patients showing aortic growth during
their follow-up. Radiology metrics have been proposed that could guide
quantification. Marui et. al (12) suggested that a fusiform index of
0.64 could be an independent predictor of adverse aortic events.
Briefly, the radiologic formula is defined as A / (B+C) where A is the
maximum diameter of the proximal descending aorta, B is the diameter of
the distal aortic arch, and C is the diameter of the descending aorta at
the anatomical level of the main pulmonary artery.
It is likely that advancing MRI techniques will improve understanding of
aortic diameter changes. Sailer et. al (23) devised the “FL
circumferential extent” (FL-CE) metric which, unlike the conventional
metrics of FL diameter and volumes, is unaffected by the position of the
aortic dissection membrane. The FL-CE itself is defined as the angular
distance between the two FL insertion points in the intimal flap - an
angle more than 249° was found to be an independent
predictor of adverse aortic events.