Discussion
The FET procedure is a promising and an evolving technique that is
associated with acceptable rates of mortality and morbidity compared to
the conventional elephant trunk procedure in the management of complex
thoracic aortic
pathologies.51 The
development of coagulopathy (i.e., reoperation for bleeding and blood
products transfusion) in aortic surgery is commonly observed in patients
undergoing repair of aneurysm or
dissection.52,53According to a position paper reported by the Vascular Domain of EACTS,
postoperative re-exploration because of bleeding ranged between
2.5-30%.54 The association between CPB or HCA
duration and perioperative coagulopathy risk is well-documented and
reported in literature. Mazzeffi et al. highlight that DHCA duration and
the need for RBC transfusion are closely associated, and that this is
even more pronounced with CPB durations between 120 and 180
minutes.55 Similarly,
decreased platelet count and function are well-documented sequelae of
pediatric cardiac and aortic reconstruction involving CPB and
DHCA.56, 57
No studies have explored the prevalence of coagulopathy specifically in
patients undergoing arch replacement using the FET technique. In their
meta-analysis, Tian et al. documented the safety and efficacy of the
frozen elephant trunk technique and reported a pooled mortality of
8.3%, stroke rate of 4.9%, and spinal cord injury rate of
5.1%.58 Though the
findings of Tian et al. are robust, our study demonstrated a strong
association between the FET procedure for total arch replacement and
perioperative coagulopathy, represented by reoperation for postoperative
bleeding and the need for blood product transfusion. 17% of the
patients included suffered postoperative bleeding, while the pooled
estimate of reoperation for postoperative bleeding was 7%.
The mean volumes of transfused packed blood cells and fresh frozen
plasma were 1677 ml and 1016 ml respectively.
The pathophysiology of surgery-induced coagulopathy in aortic operations
has not been properly described; however, it has been reported that
acute aortic dissection itself activates hemostatic systems before
surgery.23 Liu et
al59 evaluated
perioperative consumption coagulopathy among sixty-six patients with
acute type A aortic dissection against thirty-six patients with thoracic
aortic aneurysms. They demonstrated that clotting factors and fibrinogen
levels were perioperatively reduced, but platelet functions were less
changed. Nomura et al60assessed the coagulation states after type A aortic dissection surgery
and followed patients up for 82 months. In their study,
hypercoagulability was identified even in the chronic phase, as measured
by D-dimer and thrombin–antithrombin III complex. On the other hand, Li
et al61 studied
patients with aortic dissection undergoing surgical repair and found
that the relationship between the coagulation pathway and the
postoperative inflammatory reaction should be considered in future
studies. In this review, we were not able to explore any changes in
blood parameters and inflammatory markers perioperatively, but we found
a substantial need for blood product transfusion after surgery,
suggesting the paramount effects of consumption coagulopathy on patients
undergoing aortic surgeries. Further investigations about the
coagulopathy-related factors and inflammatory markers could elucidate
the proper application of such tests in the evaluation of patients
undergoing the FET procedure for aortopathies.
The volume-outcome relationship associated with FET procedures is also
worthy of discussion in the context of coagulopathy risk following FET.
Mori et al. reported that lower-volume centres (fewer than 5 cases per
year, reportedly making up 58.3% of centres) were at an increased risk
of mortality (OR 2.50, 95% CI 2.08 - 3.01, p < 0.0001)
compared to high-volume
centres.62 This is
unsurprising as greater patient volume usually translates to more
opportunities to practice intricate interventions. It has not been
conclusively demonstrated that increased operating volume in FET repair
translates to shorter CPB/HCA durations, but would it not be reasonable
to suggest that, faced with the same patient, the more experienced
surgeon would be able to accomplish the same standard of repair in a
shorter duration than a novice surgeon? This would allow rewarming to
occur earlier, and possibly therefore reducing the risk of coagulopathy
risk in FET. The effect of longitudinal surgical training in FET
implantation and device selection on postoperative outcomes could also
be investigated – indeed, much research is required to substantiate
this.
Despite the abundance of literature detailing the hemodynamic sequelae
associated with aortic repair procedures - ranging from continued
bleeding to impaired platelet function - any clinical correlation
between coagulopathies and individual FET device characteristics
hitherto remains to be
elucidated.63 In the
present review we attempted to identify factors contributing to the
development coagulopathy as well as sources of heterogeneity. Stent
length, type, and surgical acuity were associated with a reduction in
the heterogeneity of pooled estimate of reoperation for postoperative
bleeding. In addition, in meta-regression analysis we found that both
male and younger age were associated with a reduced risk of reoperation
for postoperative bleeding.
No studies have evaluated predictors of coagulopathy among patients
undergoing the FET procedure. Further investigations with a focus on
finding predictors of bleeding and of coagulation events would be of
great use to guide surgeons for risk stratification of patients
scheduled for the FET procedure. For example, FET graft size and length
is a well-known area of contention amongst aortic surgeons, and there
currently exists no consensus around on the optimal approach to hybrid
prosthesis sizing.63
Evidence on the effect of hybrid prosthesis sizing on clinical outcomes
is varied – under-sizing has been reported as falling short of
achieving an optimal seal, while over-sizing has been associated with
further intimal injury and distal stent-induced entry tears with
endoleak.64 Because
suboptimal graft sizing can potentially lead to endoleak, perhaps
necessitating reintervention to address postoperative bleeding, graft
sizing is a pertinent area for investigation as a potential predictor or
risk factor of FET-associate coagulopathy. Indeed, there exists robust
data on the relationship between neurological outcome and FET graft
sizing. For example, Preventza et al. report that stent lengths below 10
cm carried a lower risk of SCI, and Tan et al. suggest that
proximalisation of TAR to Zone 0 may be associated with improved
neurological outcomes.65,
66 Undoubtedly, a similarly nuanced appreciation of coagulopathy
predictors associated with different FET devices and sizes would be of
great benefit. This would facilitate a more holistic understanding of
the risks and benefits associated with each individual procedure and
allow a more nuanced evaluation of patient-specific needs and risks.
Apart from graft sizing, several FET devices are
available,67-71 and
their usage in clinical practice is evolving so that studies for
outcomes of such devices are being increased in
literature.51 The
globally used tetrafurcate Thoraflex Hybrid®stent-graft provides separate reimplantation of supra-aortic vessels, an
easier anastomosis to the distal aortic arch, and radio-opaque markers
in the stented part.
In the subgroup analysis, we also found that Thoraflex® and Frozenix®
had no heterogeneity compared to moderate heterogeneity depicted for the
E-vita® and the Cronus® devices. However, it’s imperative to elicit that
the wide generalization and distribution of Thoraflex Hybrid across
diverse population groups globally and in line with different ethnic
population applicability in concurrent to the streamed analysis in this
review potentially raises the standards that Thoraflex Hybrid is
considered as the gold standard. The global availability and wide
application coupled with the multiplicity of the Thoraflex Hybrid
marketing prowess and in alignment to clinical and surgical need with
single perfusion branch and multi branch configuration have been
utilized by many aortovascular surgeons who operate under diverse
healthcare systems and have been apprenticed and trained differently.
Henceforth, undoubtedly this could potentially explain the elicited
heterogeneity of this device and its coagulopathy correlative outcomes
as perceived comparatively to others FET including the Frozenix® and
Cronus®.
Our analysis also revealed that the rate of reoperation for
postoperative bleeding was the lowest the Thoraflex
Hybrid® and for the Frozenix® among
studies included in our proportional meta-analysis. Bearing these
findings in mind it is worth highlighting that in a systematic review
comparing the Thoraflex Hybrid® and
E-vita® devices, Harky et al. emphasized that
Thoraflex Hybrid® is more frequently implanted in
cases of emergent aortic repair than E-vita®.
Notwithstanding the effect of baseline patient demographics on clinical
outcomes, this supports our finding that Thoraflex Hybrid® was associated with lower rates of coagulopathy than
E-vita, with minimal
heterogeneity.72 On the
other hand, a recent report noted excessive oozing through the fabric of
stent in three patients implanted the branched Cryolife-Jotec E-vita
open NEO hybrid
prosthesis.73 The
E-vita open Neo HP has been described as having a propensity for
excessive oozing through its polyester wall, which lacks gelatin or
collagen (a key component of preventing graft porosity). This
significant limitation has been associated with poor postoperative
outlook, and Czerny et al. describe one such patient requiring 23 U of
RBC, 28 U of FFP, and 16 U of thrombocytes in the 24 hours following
surgery. The postoperative courses of the patients affected by this
porosity were complicated by factors including low cardiac output
necessitating inotropes, haemodialysis, mutli-organ failure, paraplegia,
and death.73
Though Jakob et al. argue that strategic employment of ROTEM may help
deal with the graft’s porosity, it is imperative to clinically point out
that such an approach to FET-associated coagulopathy has been tested
only on a small number of EVITA Neo, and no other FET
devices.74
The heterogeneity of coagulopathy rates associated with the
Cronus® and the E-vita® might be
attributed to the diverse patient demographics (e.g., ethnicity) among
studies reporting outcomes from E-vita® and because
many such studies failed to report the major factors causing
complications, rather than extracted variables in our meta-analysis.