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J ENDOVASC THER
2012;19:826–833
^ CLINICAL
INVESTIGATION ——————————————————————————
^
Initial Experience With the 53300-mm Proteus Embolic
Capture Angioplasty Balloon in the Treatment of
Peripheral Vascular Disease
Thomas Zeller, MD1; Andrej Schmidt, MD2; Aljoscha Rastan, MD1; Elias Noory, MD1;
Sebastian Sixt, MD1; and Dierk Scheinert, MD2
1
Department of Angiology, Universitäts-Herzzentrum Freiburg-Bad Krozingen, Germany.
2
Park-Krankenhaus Leipzig, Germany.
^
^
Purpose: To describe the use of the 53300-mm Proteus embolic capture angioplasty (ECA)
balloon catheter to reduce embolic burden in complex TASC II (TransAtlantic Inter-Society
Consensus) C and D femoropopliteal interventions.
Methods: A non-randomized safety and feasibility study was conducted at 2 centers enrolling
15 subjects (9 women; mean age 72.569.5 years, range 53–85) suffering from RutherfordBecker category 2 to 4 occlusive disease. Of the 20 lesions in 15 limbs, 16 were TASC II D and 4
were TASC II C. Average baseline stenosis was 95%612%; 16 lesions were totally occluded.
Half of the lesions were de novo, 5 were restenotic, and 5 were in-stent stenoses. Average
lesion length was 284650 mm. In addition to using the ECA device, 18 of the target lesions
were treated with stents and 4 with rotational thrombectomy devices. Distal angiography was
performed before and after use of the ECA device to locate any periprocedural embolic events.
Results: Procedural success was achieved in 100% lesions. The ECA balloon was used for
predilation in 11 lesions and for postdilation in 9. No distal embolization or flow-limiting
vessel dissections were observed despite the complex nature of the cases. Three nondevice-related complications were reported (pseudoaneurysm, myocardial infarction, acute
renal failure) and resolved without sequelae within 30 days. Analysis of the particles
recovered from 5 ECA balloons demonstrated a mean 2576185 particles, with a mean
major axial dimension of 0.5460.04 mm (range 0.11–7.54). There were a mean 7.6766.03
particles .2 mm in diameter, and all samples contained 1 to 3 particles .4 mm in diameter.
Conclusion: In this small series, the 53300-mm ECA embolic capture balloon catheter was
an effective tool for avoiding embolic events in long peripheral lesions, with a good safety
profile. The device might be considered as part of routine clinical practice for complex TASC
II C/D femoropopliteal lesions.
J Endovasc Ther. 2012;19:826–833
Key words: atherosclerosis, peripheral artery disease, superficial femoral artery, popliteal
artery, femoropopliteal segment, balloon angioplasty, complication, embolism, embolic
protection, embolic capture angioplasty balloon
^
^
Thomas Zeller is on the advisory board and has received study grants from Angioslide Ltd. Dierk Scheinert is a paid
consultant for Angioslide Ltd. and a member of their advisory board. The other authors have no commercial,
proprietary, or financial interest in any products or companies described in this article.
Corresponding author: Prof. Dr. Thomas Zeller, Universitäts-Herzzentrum Freiburg-Bad Krozingen, Suedring 15, 79189
Bad Krozingen, Germany. E-mail: [email protected]
Ó 2012 by the INTERNATIONAL SOCIETY
OF
ENDOVASCULAR SPECIALISTS
Available at www.jevt.org
J ENDOVASC THER
2012;19;826–833
The number of lower limb interventions is
growing every year worldwide, paced by the
development of novel devices and techniques
to improve procedure success.1–6 As the
techniques improve, more patients with complex lesions, multiple comorbidities, and
See commentary page 834
severe forms of peripheral artery disease
(PAD) are being considered for this kind of
minimally invasive intervention.
Efforts to minimize the risk of potential
complications, especially during high-risk
procedures, remain the cornerstone of any
treatment protocol. One of the most serious
complications of peripheral interventions is
distal embolization, which is relatively uncommon and often under-reported or underappreciated.7 Distal embolization can potentially cause occlusion of distal vessels and
subsequent lower extremity ischemia, resulting in tissue loss and even amputation.7–9
Moreover, distal embolization can increase
the complexity and duration of any procedure
and add to healthcare costs. This problem is
rarely and contradictorily described in the
literature, with incidences varying between
1.6% and 19.0% for clinically significant
embolic events,10–15 depending on underlying
patient conditions, the complexity of the
procedure (including the number of devices
used), and lesion characteristics. Acute and
subacute lesions, for example, are more likely
to cause distal embolization than chronic
ones. Some reports have demonstrated detection of distal embolic signals by continuous
transcutaneous Doppler ultrasound in up to
100% of cases.5,15
To date, no dedicated embolic protection
device (EPD) has been designed for use
during lower limbs intervention. The filters
currently approved for embolic capture in the
carotid arteries are considered expensive,
difficult to handle, and time consuming in
the lower limb vessels, so they are almost
solely used in conjunction with atherectomy
procedures. The lack of dedicated devices for
debris capture in the peripheral circulation is
one of many reasons for the inconsistent data
on periprocedural distal embolization.
PROTEUS 53300-MM ECA BALLOON
Zeller et al.
827
Recently, a novel peripheral angioplasty
balloon with embolic capture capability was
introduced. At the end of the angioplasty
phase, this unique embolic capture angioplasty (ECA) balloon folds inward and upon
deflation safely captures embolic debris that
could otherwise potentially embolize distal
vasculature.16–19 The design of the ECA
balloon allows standard balloon dilation
along with a viable option to retrieve embolic
debris during procedures. To the best of our
knowledge, no one has reported experience
with the longer 300-mm ECA balloon, so we
have retrospectively analyzed our data from
procedures performed on complex TASC II C/
D femoropopliteal lesions using the 53300mm ECA catheter.
METHODS
Study Design
A non-randomized, single-arm study was
conducted at 2 centers in accord with the
Declaration of Helsinki and approved by the
institutional ethics committees of the participating sites. The main objective of the study
was to assess the safety and performance of
the 53300-mm Proteus ECA balloon (Angioslide, Inc., Wheat Ridge, CO, USA).
Patients older than 18 years were eligible if
they had lifestyle-limiting claudication or rest
pain (Rutherford-Becker categories 2–4) referable to de novo or restenotic lesions in the
femoropopliteal segment. Other inclusion
criteria were the presence of single, bilateral,
or multiple 50% stenosis by visual estimate
on angiography that could be successfully
crossed with a guidewire and dilated. Subjects were excluded from the study if they had
tissue loss (Rutherford-Becker categories 5 or
6), contrast hypersensitivity that could not be
adequately premedicated, or intolerance to
antiplatelet, anticoagulant, or thrombolytic
medications.
Study Device
The Proteus ECA balloon is approved by
both the Food and Drug Administration and
the Conformité Européenne for use in the
lower extremity. It captures embolic material
828
PROTEUS 53300-MM ECA BALLOON
Zeller et al.
after dilation when the balloon is folded
inward upon itself by up to 50% of the original
balloon length. This creates a suction effect
that pulls embolic material into the resulting
cavity. The balloon is then retrieved through
the sheath, removing the captured material
with it.
Patient Sample
Between May and August 2011, 15 subjects
(9 women; mean age 72.569.5 years, range
53–85) were enrolled in the study. At baseline,
4 subjects presented with ischemic rest pain,
1 had moderate claudication, and 10 had
severe claudication. There were 20 TASC II C
(n¼4) and D (n¼16) lesions (15 in the superficial femoral artery and 5 involving the femoral
and popliteal arteries) in 15 limbs. The
average ankle-brachial index (ABI) in the
target limb was 0.660.2. Ten of the lesions
were de novo, 5 were restenoses, and 5 were
in-stent restenoses. Average baseline stenosis
was 95%612% per lesion (96%610% per
patient), with 13 total occlusions. Average
lesion length was 211678mm per single
lesion and 284650mm per patient. Seven
lesions were thrombotic; 7 were not calcified,
while 8 had mild calcification, 4 had moderate
calcification, and 1 had severe calcification.
ECA Procedure
The primary use of the 53300-mm Proteus
balloon catheter was at the operator’s discretion in cases where balloon angioplasty was
considered as a first-line treatment strategy,
including provisional stenting after insufficient plain balloon dilation. In all other cases,
the ECA was intended as an adjunctive
therapy to either post-dilate nitinol stents
following direct implantation or following
rotational thrombectomy. In most of the
cases, the decision was made based on the
significant risk of distal embolization in long
treated vessels. Additional devices, such as
stents, atherectomy devices, aspiration catheters, etc., were at operator discretion and
were not excluded.
All patients were administered aspirin (500
mg) prior to the procedure, as well as a single
600-mg bolus of clopidogrel. All interventions
J ENDOVASC THER
2012;19:826–833
were performed via a 7-F sheath over a 0.035inch guidewire irrespective of whether the
ECA balloon was being used primarily or
following stent implantation or rotational
thrombectomy (Rotarex system; Straub Medical, Wangs, Switzerland). Intravenous unfractionated heparin (2500–5000 units) was
administered for intraprocedural anticoagulation. Angiographic analysis was done visually,
while lesion diameter was assessed by the
primary operator prior to deployment of any
device. Runoff angiograms were obtained in
each case pre and post ECA application. After
angioplasty, all subjects were followed up to
discharge from the hospital, at which time
they were prescribed lifelong aspirin (100 mg/
d) and clopidogrel (75 mg/d) for 4 weeks.
Particle Analysis
In 5 cases, the captured embolic material
was transferred from the balloon to a filter
and stained with violet Davidson tissue marking dye (Bradley Products Inc., Bloomington,
MN, USA) for improved contrast and visualization over hematoxylin stain. The particles
were first analyzed using Photoshop CS3
(version 10.1; Adobe, San Jose, CA, USA) to
correct uneven illumination and convert the
display to a binary image, where discrete
black areas represented embolic particles.
Pixel size was converted to metric dimensions
(mm), and the Fiji Analyze Particles function of
the ImageJ software (available at http://rsb.
info.nih.gov/ij/) was deployed to determine
the overall count and major axial dimension
of each particle.
Definitions and Endpoints
Device success was defined as successful
delivery of the ECA balloon catheter to the
lesion site, successful folding inward of the
balloon, and intact retrieval. Serious adverse
events were defined as any complication
resulting in death, hospitalization, disability,
or intervention.
The primary study endpoint was the rate of
clinically significant vessel dissections and
device-related distal embolizations. The secondary endpoints were: (1) rate of acute serious
adverse events, (2) rate of adverse events
J ENDOVASC THER
2012;19;826–833
PROTEUS 53300-MM ECA BALLOON
Zeller et al.
829
Figure 1 ^ (A) Baseline angiogram of a long in-stent occlusion of the left SFA with mild calcification. (B)
Angiogram after Rotarex mechanical thrombectomy. (C) Dilation of the lesion using a single 53300-mm
Proteus device. (D) Final angiographic result.
related to device malfunctions, and (3) procedure success rate, defined as residual stenosis
,50% in the treated lesion for plain balloon
angioplasty and ,30% following stent implantation as determined by visual estimation.
RESULTS
Both procedure and device success were
100% (Figs. 1 and 2); no device malfunctions,
vessel dissections, or distal embolizations
were reported during the procedures. The
ECA balloon was used for predilation in 11
lesions and for postdilation in 9. In 4 lesions,
the balloon was used after rotational thrombectomy. In addition to the ECA balloon, 30
self-expending stents (mean 2.3160.5 patient)
were applied in 18 target lesions. The average
diameter and length of the stents were
6.4360.73 mm and 110.33642.30 mm, respectively. Twenty-one angioplasty balloon catheters (mean 4.9061.09 mm diameter and
830
PROTEUS 53300-MM ECA BALLOON
Zeller et al.
J ENDOVASC THER
2012;19:826–833
Figure 2 ^ (A) Baseline angiogram of a 30-cm de novo TASC C total occlusion of the left SFA to popliteal
artery. (B) Direct deployment of 3 Zilver PTX drug-eluting stents (73120, 63120, and 63100 mm). (C)
Postdilation of all 3 stents using a single 53300-mm Proteus device. (D) Final angiographic result.
89.52633.24 mm length) were used adjacent
to the target lesion (mean 1.6260.87 balloons
per patient). In 2 of the 11 predilation cases,
additional dilation was done using a secondary balloon prior to stenting.
Three non-device-related adverse events
were reported in 2 patients. The first was a
77-year-old hypertensive, diabetic man with
Rutherford-Becker class 3 symptoms, diabetic
nephropathy, class III renal insufficiency,
hyperlipidemia, and a history of stroke developed a pseudoaneurysm, which was resolved
by manual compression with no sequela. The
second patient was an 83-year-old hypertensive, diabetic man with Rutherford-Becker
class 4 rest pain, hyperlipidemia, obesity,
coronary artery disease, chronic obstructive
pulmonary disease, diabetic nephropathy,
and class III renal insufficiency. He suffered
an acute myocardial infarction 2 days after the
peripheral procedure and underwent successful emergent percutaneous coronary intervention. Following this second exposure to
contrast medium, he developed contrastinduced nephropathy requiring 3 hemodialysis sessions that prolonged hospitalization. At
the time of discharge, his serum creatinine
level returned to baseline.
Analysis of the particles recovered from the
5 ECA balloons examined demonstrated a
mean 2576185 particles, with a mean major
axial dimension of 0.5460.04 mm (range
0.11–7.54) per patient. There were a mean
7.6766.03 particles .2 mm in diameter per
patient. All samples contained 1 to 3 particles
.4 mm in diameter. While histopathology
was not conducted in this study, particle
texture, color, and shape suggested chronic
thrombus (Fig. 3A,B) and neointima (Fig. 3C).
DISCUSSION
According to the literature, distal embolism
occurs frequently during peripheral interventions, where complex lesions, such as thrombotic and long TASC II C/D femoropopliteal
occlusions, are associated with higher rates of
embolic events and complications in general.7,8,20 Similar to reported experiences with
the shorter Proteus devices,16–18 our small
observational series indicates that the longer
300-mm ECA balloon can be successfully
used for the treatment of long and complex
J ENDOVASC THER
2012;19;826–833
PROTEUS 53300-MM ECA BALLOON
Zeller et al.
831
Figure 3 ^ Examples of embolic debris retrieved from Proteus balloons: (A) after mechanical thrombectomy
in a Rutherford category 3, TASC C thrombotic in-stent stenosis; (B) after mechanical thrombectomy in a
Rutherford category 4, TASC D chronic total occlusion with high thrombus burden; and (C) predilation in a
Rutherford category 4, TASC D in-stent occlusion.
femoropopliteal lesions with no distal embolism.
Kudo et al.15 registered distal embolic
events detected by Doppler during peripheral
interventions in all their iliac stenting cases.
Others have reported that acute or subacute
lower limb ischemia, endovascular treatment
of chronic total occlusions, and the use of
atherectomy techniques are independent predictors of distal embolism.8,20 The SilverHawk
plaque excision atherectomy device and laser
atherectomy have both been linked to higher
rates of distal embolization, with debris
collected in distal filter-based EPDs in 20% to
50% of cases.8,14 Similarly, angioplasty with
stent implantation during infrainguinal interventions (used in the majority of cases in our
study) may also be a source of significant
embolism.7,8 Shammas et al.14 reported clinically significant embolism in nearly 30% of
angioplasty and/or stent procedures and in
90% of atherectomy procedures in the Preventing Lower Extremity Distal Embolization
Using Embolic Filter Protection (PROTECT)
registry. In another report, the same authors
demonstrated that 2.4% of captured debris
required treatment.8
Debris resulting in slow or no flow, particularly in high-risk patients with already compromised distal runoff, usually requires
further therapy. Indeed, all symptomatic
events of distal embolization should be treated immediately, as this is a potentially limbthreatening situation. The size of particle that
can cause distal embolization is estimated to
be 2 mm, and this is without considering the
volume and/or composition of the particles or
the condition of the distal vascular bed.
Clinically significant embolic events requiring pharmacological or mechanical intervention during the procedure have been reported
in up to 20% of cases.11–16 In a registry subset
analysis reported by Shammas et al.,8 distal
embolization prolonged the procedure, required more contrast use, and increased
radiation exposure, factors important to both
operators and patients. Due to the varying
nature of the embolic debris, not all rescue
procedures are successful, sometimes even
resulting in amputation.11 Rickard et al.21
reported a 37% failure rate for attempted lysis
after embolic events, and 8.3% of procedures
reported by Chalmers et al.22 required thrombectomy.
In light of the above, avoiding embolic
complications during complex peripheral interventions should be considered routinely
since it can significantly improve patient
outcomes. To date, there have been no
dedicated devices designed for embolic capture during lower limb intervention. The use
of EPDs increases procedure costs and treatment time. Moreover, particularly in complex
procedures, it has been difficult in our experience to maintain a stable position of the
typically 0.014-inch wire-based protection devices, as there is limited wire support for the
devices during introduction and retrieval.
We believe that the Proteus ECA balloon
should be applied especially in cases where
832
PROTEUS 53300-MM ECA BALLOON
Zeller et al.
the potential risk of distal embolism is high
and the need to minimize complications is
prominent. Such cases include lower extremity chronic arterial occlusions, critical limb
ischemia, long and/or thrombotic lesions,
stenting, after atherectomy, and/or patients
with poor distal runoff. It is, however, important to add that the rationale for using embolic
capture angioplasty with the Proteus device
needs to be further investigated by large-scale
clinical trials. Data from the MC-LEADER
trial23 suggest a strong correlation between
lesion complexity and amount of debris
removed with the Proteus balloon; overall,
debris was retrieved in 100% of all peripheral
interventions performed (unpublished data).
The reports by Zankar et al.16 and Hadidi et
al.18 indicate a high success rate for this
device with respect to lesion dilation and
embolic debris capture.
As for the folding mechanism of the ECA
device, the negative pressure generated may
assist in releasing loose embolic material
from the vessel wall that otherwise could
embolize during or after the procedure, with
or without major complication. Preclinical and
clinical evaluation of the technology documented no additional vessel wall injury due to
the folding mechanism.
In our study, 3 complications were reported:
pseudoaneurysm, myocardial infarction, and
acute renal failure. The latter two are recognized major complications associated with
peripheral angioplasty, along with bronchopneumonia and stroke, reported in about
2.5% of cases.23 Pseudoaneurysm is likewise
a well documented sequela of percutaneous
interventions, especially complex peripheral
procedures.24
Limitations
This study was a retrospective analysis of a
small case series and lacked comparison to
other peripheral angioplasty balloons or embolic protection strategies. Considering the
relatively low likelihood of clinically significant distal embolization, we cannot conclude
that embolization can be prevented in all
cases by using embolic capture angioplasty,
even if we found debris in all balloons
J ENDOVASC THER
2012;19:826–833
examined and had no angiographically visible
distal embolization.
Conclusion
We believe that our experience demonstrates the safe and successful use of the
long 300-mm Proteus angioplasty balloon
with embolic capture capability during complex peripheral interventions in TASC II C and
D lesions, including plaque excision and
thrombectomy procedures. The embolic capture strategy might improve safety in interventions on lesions with a high thrombus
burden, such as acute and subacute occlusions following local lysis or mechanical clot
removal. Prospective randomized studies with
a combined endpoint including peri-interventional embolic events, procedure duration,
fluoroscopy time, and procedure costs are
mandatory to define the true benefit of the
embolic capture angioplasty concept.
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