Discussion
The evolution of IMHA is very dynamic from complete resolution to aortic
dissection [10][16][17][27]. However, for
patients with uncomplicated IMHA, which is significantly more common in
Asian countries, the “wait-and-watch strategy” is the first-line
treatment because of the lower mortality with early medical therapy than
with type A aortic dissection [18-20] . However, the
development of classic aortic dissection (19%) and retrograde type A
aortic dissection (27%) are very common fatal evolutions after medical
treatment, and the need for delayed further interventions rises up to
30% within the first 6 months [18][28] . In our study,
the hospital aorta-related mortality in both groups (Table 2 )
was similar to that reported by Song et al. [18] (7.9%)
and lower than that reported by Sandhu et al [28] (12%).
Newly diagnosed type 2 DM patients with IMHA probably benefit from
antidiabetic treatments and DM is possibly a protective factor for IMHA
during the chronic phase (>90 days) whereas tight glycemic
control may influence the evolution of IMHA at the acute phase
(<14 days) (Figure 4D ). The potentially protective
value of DM has been well described [ 4-7], and the
possible explanations included the increasing matrix of the aortic wall
(suppression of plasmin and decreased levels/activity of MMP-2 and
MMP-9), and decreased aortic mural macrophage infiltration and
neovascularization [12] . MMP-9 is involved in tissue
degradation and remodeling in aortic dissection and is significantly
increased in aortic dissection patients, and a higher level of MMP-9 can
weaken the aortic media by degrading multiple extracellular components;
DM patients have a 2-fold decreased level of MMP-9, which may restrict
the degradation of the aortic wall [12]. Tan et al[29] demonstrated that MMP-9 may be a useful biomarker for
aortic dissection. In our study, the MMP-9 level in the DM group was
lower than that in the no DM group (P< 0. 001,Figure 2 ) especially one year after the onset of IMHA. However,
all three deaths during the acute phase occurred in the DM group
(although there were no significant differences) even though the MMP-9
level was obviously lower (Figure 2 , Figure 4D ) than
that in the no DM group. The probable explanation is that insulin
treatment may diminish this protective effect of hyperglycemia that
prevent the aortic aneurysm development process (under laboratory
conditions) [14]; after receiving tight glycemic control
recommended by guidelines [1][11][22], theDM group had an MMP-9 level that was dramatically increased
(reached the highest value) during the acute phase, which probably
indicated the potentially decreased protective effect of hyperglycemia.
Rupture of retrograde type A aortic dissection and ascending aortic
pseudoaneurysm after receiving TEVAR were the main causes of death in
our study. The explanation for these complications is the choice of
TEVAR devices, stent graft landing zones and commitment arch
reconstruction surgery which can probably influence the outcomes after
TEVAR. Although we avoided balloon dilatation because of the potential
risk of retrograde type A aortic dissection [25] , we did
have one patient who probably died of retrograde type A aortic
dissection after balloon dilation (Patient 4, Supplement 2 ).
Additionally, we employed only stent grafts with a proximal bare spring
design. Although non-proximal bare-spring stent grafts yield a similar
incidence of retrograde type A aortic dissection [25],proximal bare-spring stent grafts have long been regarded as a risk
factor and may injure the fragile aortic wall, resulting in the
development of retrograde type A aortic dissection [26] .
Moreover, in our study, intramural hematomas that affected the aortic
arch without obvious entry tears characterized as aortic dissection
always required arch revascularization. However, the partial occlusion
clamp may injure the fragile aortic wall (during the debranching
procedure) and cause further damage that results in lethal complications[29] ( Patient 16, Supplement 2). In addition, a
dilated ascending aorta (> 4 cm) (Patients 6,8,9 and 12,Supplement 2 ) and TEVAR in the chronic phase are potential risk
factors for fatal complications after TEVAR [30][31].Additionally, five patients died of aorta-related complications
complaining of refractory pain after TEVAR (Patients 5, 6, 8, 9 and 10,Supplement 2 ). Juvonen, et al [32] reported that
chest or back pain is predictive of aortic rupture, and that patients
with uncharacteristic or atypical pain have a higher risk of rupture
over time, and that medical management is unwarranted for these patients[33] . In sum, for IMHA, it seems logical to recommend
prophylactic replacement of the aortic wall that presented the
intramural hemorrhage, because of the risk of fatal complications
especially for those with a dilated aorta, intramural hematomas that
affect the aortic arch, and refractory pain after TEVAR.
In the “wait-and-watch strategy” the interval of the imaging
evaluation is also important. Kitai, et al recommended careful serial
imaging because conventional 5-mm axial images may not completely
identify ulcer-like projections (ULPs) smaller than 5 mm[34] . Thus, with low-resolution computed tomography scan
results, simply equating the lack of a ULP with a favorable prognosis is
probably unjustified, and a more precise CTA scan and closer monitoring
for the development of a ULP are necessary. Moreover, intravascular
ultrasonography [16] is another meaningful examination
method that permits a dynamic real-time evaluation of the aorta and can
detect the origin of side branches, evaluate adequate expansion after
the deployment of the stent graft and exclude potential complications
(such as retrograde type A aortic dissection occurring
intraoperatively).
There are several limitations of this study. First, future longitudinal
prospective investigations with a multicenter cooperation focusing on
more patients are necessary. Second, techniques (such as TEVAR devices
and arch reconstruction methods) probably affect patient outcomes, and
further studies are required for a more standardized and uniform
management strategy. Third, the anti-inflammatory effect of oral
antidiabetic medication drugs could lower the risk of fatal progression[13], and the enrollment of more patients with different
medical treatment strategies (insulin with/without oral antidiabetic
medication drugs) may provide more meaningful insight into this
question.