SEAL - Safety & Feasibility Evaluation of the Aortoseal Endostapling System for seal and fixation of abdominal aortic aneurysms (AAA) endovascular grafts to the aortic wall

Abdominal aortic aneurysm (AAA) is a focal enlargement of the abdominal aorta
such that the diameter
is greater than 3 cm or more than 50% larger than normal (1). Approximately 80%
of aortic aneurysms
occur between the renal arteries and the aortic bifurcation. Aneurysms develop
as a result of
degeneration of the arterial media and elastic tissues. Risk factors for AAA
are similar to those of(2)
other cardiovascular diseases. The key risk factors are male gender, smoking,
age older than 65 years,
coronary artery disease, hypertension, previous myocardial infarction,
peripheral arterial disease, and a
family history of AAA. The prevalence of AAA increases with age. It is uncommon
in persons younger
than 50 years; however, 12.5% of men and 5.2% of women 74 to 84 years of age
have AAA (3).
The natural history of AAA is to enlarge slowly over years. AAA of 4.0-5.5 cm
grow at a rate of 0.3
cm/year with less than 25% enlarging 0.5 cm or more per year with larger
aneurysms expanding more
quickly than smaller ones. The main risk of an untreated AAA is progressive
expansion, leading to
aneurysm rupture or aortic dissection and eventually to death. Rupture occurs
most commonly into the
retroperitoneal space; aneurysms may also bleed into the pleural space,
gastrointestinal tract, inferior
vena cava, or left renal vein. Symptoms of rupture include abdominal or back
pain, hypotension, and a
tender abdominal mass. Embolism of thrombus may result in occlusion of lower
limbs. Additional
complications include infection, and embolization. Only about 50% of patients
with ruptured AAAs
reach the hospital alive, and for those who reach the hospital, 50% do not
survive repair treatment (4).
AAAs account for approximately 11,000 deaths each year in the United States,
with mortality rates
from ruptured AAAs reaching up to 90% (5).
Aneurysms producing symptoms, especially pain and tenderness on palpation, are
at increased risk for
rupture. AAAs can also present with complications due to thrombosis,
embolization or, rarely, as
clinically overt disseminated intravascular coagulation causing hemorrhagic and
thrombotic
complications.
The majority of AAAs are asymptomatic and are most often detected as an
incidental finding on
ultrasonography (USG), abdominal computed tomography (CT) or magnetic resonance
imaging
performed for other purposes. Most AAAs are silent until they rupture, although
some (30%) are
identified during evaluation for abdominal symptoms.
The U.S. Preventive Services Task Force (USPSTF) updated its 2005 guideline on
ultrasonography
screening for AAA. The USPSTF continues to recommend one-time screening with
ultrasonography
for men 65 to 75 years of age with a history of smoking and women 65 years or
older who have smoked
or have a family history of AAA(6). The natural history of AAA shows that as
aneurysms increase in
size, they expand at a greater rate and the risk of rupture increases.
Therefore, in persons found to have
aneurysms, regular surveillance is needed every six months to three years,
depending on aneurysm size.

3.2. Standard of Care (Patients with an Asymptomatic AAA)
For AAA, diameter is the most important factor predisposing to rupture. The
risk increases significantly
for aneurysm diameters greater than 5 cm for women and 5.5 cm for men (7). An
aortic diameter of 5.5
cm is currently considered the threshold for repair in an *average* healthy
patient (8). The primary
goal in the management of AAAs is to slow the expansion rate and reduce the
risk of dissection or
rupture. Management options for patients with an asymptomatic AAA include
observation with followup/medical therapy, open surgical repair and
endovascular repair. Each of these options is described in
more detail below:
Medical Therapy/Observation: There is general agreement that small aneurysms,
<4.0 cm in
maximum diameter, are at low risk of rupture and should be monitored. Several
approaches have been
proposed by the US society of vascular surgery to prevent further enlargement.
Smoking cessation is
the most important intervention for a patient with an aneurysm. Patients should
be encouraged to seek
appropriate medical management for hypertension, hyperlipidemia, diabetes, and
other atherosclerotic
risk factors. A statin and ACE inhibitor should be considered, given the broad
potential benefits to
cardiovascular disease and acceptable safety profile. Insufficient data
currently exist to recommend use
of doxycycline or roxithromycin. Patients should be counseled that moderate
physical activity does not
precipitate rupture or influence AAA growth rate. (9)
The US SVS guidelines recommend that aneurysms >4.9 cm in diameter in women and
>5.4 cm in
diameter in men should be repaired in an otherwise healthy patients. Elective
repair is also
recommended for patients who present with a saccular aneurysm, and although
size guidelines are
currently lacking because of their infrequent presentation, repair is generally
recommended at a smaller
diameter. (9)

Open Surgical Repair OSR:
The traditional treatment for AAA is elective open surgery that involves
a large abdominal incision and placement of a synthetic graft sutured from the
proximal end of the
aneurysm to the distal aorta or iliac segments. Flow is then restored to the
lower extremities and the
aneurysm sac is closed over the graft. The graft materials used in stent grafts
are typically polyester or
expanded polytetrafluoroethylene (ePTFE). It can be expected that surgical
repair will be very durable
and protect from AAA rupture for the lifetime of the patient.(10-14)
Endovascular Repair: The EVAR procedure is a minimally invasive repair
technique performed under
aortography, in which a stent graft (endovascular graft) is inserted through
the femoral and iliac arteries
to the location of the aneurysm using a delivery system. It was first performed
by Parodi et al. in 1991
using a Dacron graft sutured onto balloon expandable Palmaz-Schatz stent.
Endovascular stent grafts
rely on radial forces from self-expanding stents for fixation (passive
fixation) or self-expansion with
the addition of hooks or barbs (active fixation) to position and secure the
device to the aorta. These
devices are designed to prevent aortic pulsatile flow and sheer stresses from
being transmitted to the
aneurysmal sac.

To be a suitable candidate for EVAR, certain general anatomic criteria must be
fulfilled including an
aortic aneurysm proximal neck diameter that measures 18-32 mm in diameter and
is generally
greater than 10 mm in length, a neck angulation that is typically less than 45-
60 degrees (depending
on the endovascular graft used), a common iliac artery diameter between 8-22 mm
and an external iliac
diameter greater than 7 mm. Anatomy generally unfavorable for EVAR include
various anatomic
features such as excessive aortic tortuosity and angulation, a hostile proximal
neck with
circumferential calcification, excessive mural thrombus, an extremely conical
configuration, and
extremely small-caliber access vessels. There are also other considerations
such as the patient*s
inability or unwillingness to comply with post-procedural surveillance imaging.
Compared with open surgical repair, EVAR is associated with lower operative
mortality risk, lower
perioperative morbidity faster recovery time, and shorter hospital stays (15)
(16). Conversely, OSR is
known to be more durable and the repair is likely to last for the rest of the
patient*s lifetime

The objective of the SEAL Early Feasibility Study (STUDY) is to provide proof
of concept and initial
clinical safety data for the Aortoseal Endostapling System for the fixation and
seal of abdominal aortic
aneurysms (AAA) endovascular grafts to the aortic wall.
Data from this study will inform a future pivotal clinical study.

The clinical study is a prospective, non-randomized, single arm, multi-center,
open-label Early
Feasibility Study that is designed to provide initial clinical safety data
regarding the Aortoseal
Endostapling System.

Open Surgical Repair OSR:
The traditional treatment for AAA is elective open surgery that involves
a large abdominal incision and placement of a synthetic graft sutured from the
proximal end of the
aneurysm to the distal aorta or iliac segments. Flow is then restored to the
lower extremities and the
aneurysm sac is closed over the graft. The graft materials used in stent grafts
are typically polyester or
expanded polytetrafluoroethylene (ePTFE). It can be expected that surgical
repair will be very durable
and protect from AAA rupture for the lifetime of the patient.(10-14

The investigational device is used as an adjunct to endovascular exclusion of
an abdominal aortic
aneurysm. There are risks associated with the interaction of the
investigational device and the
endovascular graft, as well as the risks associated with a failure to provide
adequate fixation and seal
between the endovascular graft and the aortic neck.

The following device-specific potential risks may possibly be caused by, or
associated with, the use of
the investigational device:
• Endovascular graft migration
• Type Ia or III endoleak
• Aneurysm expansion
• Aneurysm rupture.
These observations may require secondary interventions. If left untreated,
aneurysm rupture is likely to
result in death.
The following risks may possibly be caused by, or associated with, the
investigational device implant
procedure:
• Endovascular graft migration
• Type Ia or III endoleak
• Vascular trauma
• Thromboembolic events