Transcatheter closure of patent ductus arteriosus with a self-expanding platinum-coated nitinol device.

Abstract

An occluding device for closure of patent ductus arteriosus (PDA) was developed from meshed nitinol wires coated with platinum for prevention of nickel release after implantation.
Our purpose was to assess the immediate and short-term results of transcatheter PDA closure with this device.
Sixty patients (13 males and 47 females) underwent catheter-based PDA closure. The age ranged from 9 months to 65 years, with a median age of 4 years. The weight ranged from 4.2-65 kg, with a median of 15.2 kg. The mean PDA diameter at the narrowest segment was 4.7 +/- 2.2 mm, with a range of 2.0-15.1 mm. Eighteen cases had serial blood samples for serum nickel analysis taken before and at 1, 3 and 30 days after device implantation.
The devices were successfully deployed in all 60 patients. There were no serious procedural complications. Color Doppler demonstrated complete occlusion rate of 78.3%, 90.0% and 100% at 1 day, 1 month and 1 year after implantation, respectively. There was no statistical difference in serum nickel concentrations between pre- and post-implantation.
Transcatheter PDA closure using a platinum-coated nitinol device can be performed safely and successfully. There was no evidence of nickel release or nickel reaction after device implantation. This device model may be an alternative for PDA closure, especially in patients with potential nickel allergy.

Full text

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286The Journal of Invasive Cardiology
Original Contribution
ABSTRACT: Background. An occluding device for closure of
patent ductus arteriosus (PDA) was developed from meshed nitinol
wires coated with platinum for prevention of nickel release after im-
plantation. Objectives. Our purpose was to assess the immediate and
short-term results of transcatheter PDA closure with this device.
Methods. Sixty patients (13 males and 47 females) underwent catheter-
based PDA closure. The age ranged from 9 months to 65 years, with a
median age of 4 years. The weight ranged from 4.2–65 kg, with a median
of 15.2 kg. The mean PDA diameter at the narrowest segment was 4.7
± 2.2 mm, with a range of 2.0–15.1 mm. Eighteen cases had serial blood
samples for serum nickel analysis taken before and at 1, 3 and 30 days
after device implantation. Results. The devices were successfully de-
ployed in all 60 patients. There were no serious procedural complica-
tions. Color Doppler demonstrated complete occlusion rate of 78.3%,
90.0% and 100% at 1 day, 1 month and 1 year after implantation, re-
spectively. There was no statistical difference in serum nickel concentra-
tions between pre- and post-implantation. Conclusion. Transcatheter
PDA closure using a platinum-coated nitinol device can be performed
safely and successfully. There was no evidence of nickel release or nickel
reaction after device implantation. This device model may be an alterna-
tive for PDA closure, especially in patients with potential nickel allergy.
J INVASIVE CARDIOL 2009;21:286–289
Key words: patent ductus arteriosus; transcatheter closure;
platinum-coated nitinol device; nickel release
Nitinol, an alloy composed of 55% nickel and 45% tita-
nium, has been widely applied in many medical implant prod-
ucts. During the past decade, a variety of nitinol-containing
devices were designed and studied for catheter-based closure of
atrial septal defect (ASD), patent foramen ovale (PFO) and
patent ductus arteriosus (PDA). At present, Amplatzer occlud-
ers (nitinol-containing devices) have been used worldwide for
transcatheter closure of ASD, PFO and PDA. A large amount
of literature exists indicating excellent outcomes, even in very
large defects.1-8For the nickel component in nitinol alloy, tran-
sient release of nickel into the circulation was demonstrated
after ASD and PFO closure with the Amplatzer occluder (AGA
Medical Corp., Plymouth, Minnesota).9,10There were a number of
reported cases about systemic allergic reaction after closure of
ASD, PFO11–13and PDA14with a nitinol-containing device.
Thus, nickel release after nitinol device implantation is a con-
cern, especially in patients with a history of nickel allergy. With
nanotechnology, ultrathin layers of platinum coated on the sur-
face of nitinol can avoid exposure of the nickel-containing alloy
to the bloodstream and also prevent nickel release after device
implantation. This concept presents an innovative model of a
nitinol-based PDA occlusion device that is platinum-coated for
prevention of nickel reaction after implantation. This device may
be an alternative for PDA closure, especially in patients who have
clinical evidence of nickel allergy, or in those who would like to
avoid the possible adverse effects from nickel reaction.
The purpose of this study was to evaluate the immediate and
short-term outcomes of transcatheter PDA closure with a
platinum-coated nitinol device and to study the serial serum
nickel concentrations before and after device implantation.
Methods
Patient population. The study protocol and informed con-
sent form were approved by the ethics committee of the Faculty
of Medicine, Chulalongkorn University, Bangkok, Thailand. The
consent forms were signed by the patients or their parents for par-
ticipation in the study. Patients beyond the neonate age who were
diagnosed by clinical and echocardiographic findings with a PDA
requiring closure were invited to participate in the study. Between
August 2005 and April 2008, 60 patients (13 males and 47 fe-
males; 49 pediatric and 11 adult cases) were enrolled in the study.
The median age was 4 years (range: 9 months to 65 years). The
median weight was 15.2 kg (range: 4.2–65 kg).
Device design. The system consists of an occlusion device,
a delivery cable and a loader. The device is braided with nitinol
wires, nanocoated with platinum and filled with 5 polypropy-
lene sheaths to enhance thrombogenicity (Figure 1). A delivery
cable can be connected to the proximal end of the device with
a screw connection for controlled release. The device is tubular
in shape, with a diameter 2 mm larger at the distal end than at
the proximal end. A thin disc is located on the distal end, which
has a diameter 4 mm larger than that of the distal end. The size
of the device is indicated by the diameter of its smaller proximal
end. We demonstrated the safety and successful occlusion results
with this device in our previous animal experiment.15Although
this device appears similar to the Amplatzer Ductal Occluder,
Transcatheter Closure of Patent Ductus Arteriosus with a
Self-Expanding Platinum-Coated Nitinol Device
Pornthep Lertsapcharoen, MD, Apichai Khongphatthanayothin, MD, Vidhavas La-orkhun, MD,
Kanyalak Vithessonthi, MD,
*Suphot Srimahachota, MD
From the Division of Pediatric Cardiology, Department of Pediatrics, and the
*Division of Cardiology, Department of Medicine, Faculty of Medicine, Chula-
longkorn University, Bangkok, Thailand.
This study was funded by Vascular Innovations Co. Ltd. No funding was re-
ceived for the preparation of this manuscript.
Manuscript submitted December 2, 2008, provisional acceptance given Decem-
ber 31, 2008, final version accepted January 19, 2009.
Address for correspondence: Pornthep Lertsapcharoen, MD, Division of Pedi-
atric Cardiology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn
University, Bangkok 10330, Thailand. E-mail: lpornthep@yahoo.com

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Transcatheter Closure of Patent Ductus Arteriosus
Vol. 21, No. 6, June 2009 287
the size of the precoated nitinol wires, the platinum coating on
the surface of the meshed nitinol wires and the fabric used in-
side differentiate it from the Amplatzer device.
Closure protocol. Under intravenous midazolam and fen-
tanyl sedation, conventional right- and left-heart catheterization
was performed for hemodynamic assessment. Right anterior
oblique and lateral aortograms were obtained to evaluate PDA
size and morphology. The closure device size was selected by
using 2–3 mm larger than the narrowest PDA diameter meas-
ured in the lateral aortogram. The device was loaded into a long
vascular sheath that was previously introduced via a femoral
vein to the right heart, pulmonary artery and through the duc-
tus into the descending aorta. It was then deployed with the
distal thin disc at the aortic end, the body stenting at the nar-
rowest part of the ductus, and the proximal end minimally pro-
truding into the pulmonary artery. Aortography was performed
after device deployment to assess its position and alignment.
After the finding was satisfactory, the delivery cable was un-
screwed to detach from the device. Another aortogram was per-
formed to assess the occlusion (Figure 2).
Serum nickel analysis. Serial blood samples for serum
nickel concentrations were collected from 18 patients prepro-
cedure and 1 day, 3 days and 1 month after implantation. Sam-
ples from 100 normal subjects were also collected as a control.
The blood was centrifuged immediately and the serum collec-
tion was frozen at -20°C until analysis was performed. Serum
nickel analysis was conducted by electrothermal atomic absorp-
tion spectrophotometry (ETAAS), the same technique as pre-
viously reported.16
Statistical analysis. Data were expressed as mean ± stan-
dard deviation. The serum nickel levels after implantation were
compared to the preimplantation baseline by using the paired
t-test. The difference in nickel concentrations in the patients
and normal subjects was analyzed by the independent samples
t-test. A p-value < 0.05 was considered statistically significant.
Results
The devices were successfully deployed in all 60 patients.
The narrowest PDA diameter by lateral aortography ranged
from 2–15.1 mm, with a mean of 4.6 ± 2.2 mm. Device size
ranged from 4–18 mm, with a mean of 7.0 ± 2.3 mm. The as-
sociated lesions were mild aortic stenosis in 3 cases, mild pul-
monic stenosis in 1 case, a small atrial septal defect (ASD) in 1
case, and post pacemaker implantation for congenital heart
block in 1 case. One patient, who had a residual PDA of 3.4
mm after surgical ligation, was also included in the study. No
serious procedure-related complications occurred.
During the mean follow-up period of 13.2 ± 11.3 months
(range: 1–37 months), all the patients were doing well. One pa-
tient had minimal protrusion of the device into the aorta. No
other device-related complications were noted. Two-dimensional
and color Doppler echocardiographic studies revealed complete
occlusion rates of 78.3% (47 patients) at 1 day, 90.0% (54 pa-
tients) at 1 month, 93.3% (56 patients) at 6 months, and 100%
(60 patients) at 12 months post implantation. The patient who
had minimal protrusion of the device into the aorta was a 4.2
kg, 10-month-old girl who had a 3.6 mm PDA closed using a
6 mm device. At 1-year follow up, color Doppler demonstrated
flow velocity of 1.22 m/second (pressure gradient of 6.0
mmHg) across the descending aorta, but there was no differ-
ence in noninvasive blood pressure measurement obtained from
both upper and lower extremities. The largest PDA case (15.1
mm) was a 13-year-old girl who weighed 37 kg.
She had severe pulmonary hypertension, with a
mean pulmonary pressure of 85 mmHg prior to
PDA occlusion. An 18 mm device was success-
fully deployed, and her mean pulmonary pres-
sure declined to 52 mmHg immediately after
occlusion. Color Doppler echocardiography
Figure 1. The platinum-coated nitinol patent ductus arteriosus device
is attached with the delivery cable by screw connection.
Figure 2. Aortograms in the right anterior oblique
(upper panels) and lateral (lower panels) views of a 9-
month-old girl. The left panels were the pre-implantation
aortogram to evaluate patent ductus arteriosus (PDA)
morphology and measure PDA narrowest diameter (4.2
mm in lateral view). The middle panels show proper po-
sition and alignment of a 6-mm device that was still at-
tached to the delivery cable. The right panels reveal
complete occlusion after the device was released from
the delivery cable.

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LERTSAPCHAROEN, et al.
288
The Journal of Invasive Cardiology
demonstrated complete PDA closure 1 day after implantation.
Seven months after device occlusion, a second cardiac catheteri-
zation was performed to evaluate the patient’s pulmonary pres-
sure. The patient still had residual pulmonary hypertension, with
a mean pulmonary pressure of 44 mmHg. Repeat aortography
demonstrated proper position and alignment of the device and
complete PDA occlusion (Figure 3).
Eighteen patients who underwent serial blood sample col-
lection for serum nickel analysis had a mean PDA size of 5.3 ±
3.0 mm and a mean device size of 7.9 ± 3.0 mm. The mean
serum nickel levels at baseline (n = 18), day-1 (n = 14), day-3
(n = 13), and day-30 (n = 13) were 0.59 ± 0.19, 0.57 ± 0.18,
0.57 ± 0.15, and 0.68 ± 0.27 ng/ml, respectively. There was no
statistical difference in serum nickel concentrations between the
pre- and post-implantation measurements (Figure 4). P-values
comparing mean pre-implantation with mean post-implanta-
tion levels at day-1, day-3, and day-30 were 1.0, 0.51 and 0.55,
respectively. The mean serum nickel levels in the study patients
(pre- and post-implantation serum levels of 58 samples) were
not statistically different from those of the 100 control subjects
(0.57 ± 0.21 vs. 0.60 ± 0.30 ng/ml), with a p-value of 0.53.
Discussion
Amplatzer devices have been widely used for ASD, PFO and
PDA closure during the past decade with excellent outcomes.1-
8Reports by Ries et al9and Burian et al10described the signifi-
cant increase in serum nickel levels after transcatheter closure of
ASDs and PFOs with Amplatzer ASD and PFO occluders. The
nickel release occurred transiently for a period of 3–6 months
after device implantation. Calcium-phosphate layer formation
on the passive oxide film of the nitinol wires or neoendothe-
lialization on the surface of the implanted device may explain
the drop to normal levels.9,10There are also reported cases on
systemic allergic reaction after nitinol-containing device im-
plantation for ASD and PFO closure.11–13Recently, Kim et al14
reported a case of a 31-year-old female who developed general-
ized pruritic erythematous maculopapular skin eruption on the
day following PDA closure with an Amplatzer Ductal Occluder.
The patient was treated with prednisone 40 mg daily and the
skin lesion disappeared after several days. An allergic skin patch
test revealed a strong positive reaction to nickel. Overall, a small
number of cases have been reported in which patients devel-
oped a systemic allergic reaction after nitinol-based device im-
plantation compared to the very large number of implant cases,
but practitioners should be aware of the potential for this type
of allergic reaction, especially in patients with nickel allergy.
Rigatelli et al17reported on 8 out of 9 patients with proven
nickel allergy who developed a sort of “device syndrome” 1–2
days after ASD or PFO closure with full-nitinol devices such
as the Amplatzer ASD and PFO occluders or a low-dose-nitinol
device such as the Premere™PFO Closure System (St. Jude
Medical, Inc., St. Paul, Minnesota). The syndrome included con-
current chest discomfort, exertional dyspnea, asthenia and mild
leukocytosis in the absence of arrhythmia, instrumental peri-
cardial inflammation or effusion, device thrombosis or femoral
vascular complication. Interestingly, none of the other 37 pa-
tients without nickel allergy developed the post-closure symp-
toms similar to those of the nickel allergy patients. It would
appear that nickel was released from the surface of the nitinol
wires into the circulation after implantation. The phenomenon
ceased once the device was endothelialized or after a calcium-
phosphate layer had formed on the passive oxide film of the
nitinol wires.9,10This is where platinum activation of the nitinol
surface by nanotechnology becomes relevant. Nanotechnology
makes it possible to deposit layers of platinum atoms over the
surface of meshed nitinol wires by a process called plasma dep-
osition. The platinum-coating layer creates a biocompatible and
noncorrosive zone, which can prevent the adverse effects from
nickel release. In addition, it also preserves the superelastic and
shape-memory properties of nitinol. Even though the platinum-
coated nitinol PDA device in this study appears similar to that
of the Amplatzer Ductal Occluder, several changes are apparent
from an engineering standpoint. For example, the wires are of a
different thickness than those of the Amplatzer Ductal Occluder
and are platinum-coated after the device is formed. Further-
more, the fabric used inside the device is spunbound polypropy-
lene. The platinum-coated nitinol PDA device is an innovative
model designed to solve the nickel-reaction problem. We pre-
sented our previous study on transcatheter ASD closure using a
nanoplatinum-coated nitinol ASD device.16
The platinum-coated nitinol device avoids nickel exposure
including nickel adverse effects; it also yields results equal to
those of a bare-nitinol device. In this study, successful implan-
tations occurred in all attempted cases, with a complete closure
rate of 90% within 1 month, and 100% within 1 year after the
Figure 3. Aortograms in right anterior oblique (upper panels) and lateral
(lower panels) views of a 13-year-old girl with 15.1 mm patent ductus ar-
teriosus that was closed with an 18-mm device. The left panels were before
implantation. The right panels were at 7 months after implantation.

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Transcatheter Closure of Patent Ductus Arteriosus
Vol. 21, No. 6, June 2009289
procedure. In our smallest patient (a 4.2 kg girl with a 3.6 mm
PDA), there was even minimal protrusion of the device into the
descending aorta. She was doing well and weighed 8.3 kg at 1-
year follow up. Our largest PDA case (15.1 mm) had a preclosure
mean pulmonary pressure of 85 mmHg; despite a large PDA and
elevated pulmonary pressure, an 18 mm device was successfully
deployed. Although the device has a single disc placed on the
aortic end and no disc on the pulmonary end, it can tolerate
high pulmonary pressure in the event of pulmonary hyperten-
sion. This finding supports the feasibility of this device model
for safe implantation in large PDAs with pulmonary hyperten-
sion. The procedure was performed by upsizing the device so
that the body stented tightly within the PDA and the device’s
proximal end (which protruded into the pulmonary artery) was
large enough to tolerate the elevated pulmonary pressure.
We did not study the serum nickel levels in patients after
implantation of the Amplatzer Ductal Occluder as a relative
comparator. This is our early experience in catheter-based PDA
closure with an occlusion device. However, our study has demon-
strated no difference in nickel levels between pre- and post-im-
plantation, even in the case where an 18-mm device was
deployed. There was no report of nickel release after implantation
of the Amplatzer Ductal Occluder. In addition, the size, as well
as the amount of nitinol in the Amplatzer Ductal Occluder, are
much smaller than those of the Amplatzer ASD and PFO occlud-
ers. However, there was at least one reported case of allergic der-
matitis after Amplatzer Ductal Occluder implantation in a female
patient whose allergic skin patch test was strongly positive for
nickel.14Furthermore, it has been demonstrated that an allergic
reaction could occur after implantation of Amplatzer devices that
are entirely composed of nitinol as well as other devices that are
partially comprised of nitinol.17This should mean that the allergic
reaction does not depend on the amount of nitinol in the device.
During follow up, we had no clinical information that suggested
any other device-related complications, including potential
nickel-related reactions. These findings support the notion that
nickel release can be prevented by platinum coating on the niti-
nol surface. However, further studies are needed to test for pos-
sible device-related adverse effects.
Conclusion
Transcatheter PDA closure using a platinum-coated nitinol
PDA device can be performed safely and successfully with good
results. Serum nickel analysis suggested no evidence of nickel
release after implantation. Our patients developed no symp-
toms or signs suggesting a nickel reaction during follow up.
This device may be an alternative for catheter-based PDA clo-
sure, especially in patients with a potential allergy to nickel.
Acknowledgement. Serum nickel analysis was conducted
in the Department of Clinical Chemistry, Faculty of Medical
Technology, Mahidol University, Bangkok, Thailand. We wish
to thank Mr. Lerson Suwannathon for his cooperation and
valuable assistance with the methodology.
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Figure 4. Serum nickel levels pre- and post- implantation.
Mean (error bars: 1 standard deviation)
ng/ml
Pre- Day 1 Day 3 Day 30
1.2
1.0
0.8
0.6
0.4
0.2
0.0