Journal of Pediatric Cardiology and Cardiac Surgery 3(1): 1‒7 (2019)

Original Article

A Clinical Survey on Current Status of Ductal Stenting
in Congenital Heart Disease in Japan
Masataka Kitano, MD, Hisashi Sugiyama, MD, PhD, Kenji Baba, MD, PhD,
Hirotaka Ohki, MD, Koichi Kataoka, MD, PhD, Kiyohiro Takigiku, MD, PhD,
Yasushi Misaki, MD, and Hideshi Tomita, MD, PhD
Department of Health Insurance Committee, Japanese Society of Pediatric Interventional Cardiology, Osaka, Japan

Background: Although ductal stenting (DS) has been performed in patients with severe congenital heart diseasein Japan, the frequency of DS performed in Japan remains unclear; moreover, no stent has been approved forarterial duct (AD) under Japanese health insurance (JHI).
Methods: The Health Insurance Committee of the Japanese Society of Pediatric Interventional Cardiology conducted a questionnaire-based survey to investigate the current status of DS performed and its necessity in Japanand evaluated the eﬃcacy and safety of the procedure to seek approval for its use under JHI.
Results: DS was performed in 64 cases at 12 institutions between April 2013 and March 2016. A total of 62 DS
were performed for restoring the systemic circulation in patients with hypoplastic left heart syndrome, subaortic
stenosis with interrupted aortic arch, and others. The three major indications for performing DS were high riskof alternative surgery such as the Norwood procedure, urgent procedures owing to the closure of AD, and basedon own institutional principle. Complete success was achieved in all the 62 procedures, and prostaglandin E1
was withdrawn in 60 cases (97%). Major complications included stent migration/embolization in 6 cases (9.7%),
4 of which were replaced using a balloon, and dissection in 3 cases (4.8%). Mortality related to the procedures orcomplications was absent. Majority of the patients reached the next stage surgery.
Conclusions: The present study strongly recommends that both balloon-expandable and self-expandable stents
must be approved for the safe and eﬀective ductal intervention under JHI as soon as possible.

Keywords: oﬀ-label use, congenital heart disease, ductal stenting, Norwood, hypoplastic left heart
syndrome

Introduction
Surgical outcomes of the Norwood procedure forhypoplastic left heart syndrome (HLHS) have significantly improved over the past two decades1‒4); however, a high mortality rate of approximately 45% has
been associated with high-risk neonates undergoing
this clinical procedure.3, 4) Moreover, interstage morbidity and mortality related to the shunt stenosis werereported after Norwood procedure, especially with theSano modification.5, 6) A hybrid approach comprisingbilateral pulmonary artery banding and ductal stenting(DS) has emerged as a less invasive palliative strategy7, 8)
and improved the outcome of high-risk neonates with
HLHS.9, 10)
At present, Sinus-SuperFlex-DS stent is available for
DS mainly in European countries, which is the only one
approved for arterial duct (AD) in the world.11) Therefore, in the countries where this stent is not available, DS
is performed using oﬀ-label stents for peripheral vessels,
renal artery, or biliary duct, as with a situation of a nonlicensed drug use in diﬀerent settings worldwide. Concerning the situation in Japan, DS has been frequently
performed in patients with HLHS and other congenital

Received: November 4, 2017; Accepted: May 8, 2018
Corresponding author: Masataka Kitano, MD, Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center,5‒7‒1, Fujishirodai, Suita, Osaka 565‒0873, Japan
E-mail: kitanom@hsp.ncvc.go.jp
doi: 10.24509/jpccs.190101© 2019 Japanese Society of Pediatric Cardiology and Cardiac Surgery

2heart diseases with duct-dependent systemic circulation;
however, no stent has been approved for AD under Japanese health insurance (JHI).12, 13) Therefore, in the present study, we conducted a questionnaire-based survey
to investigate the current status of DS and its necessity
in Japan in routine clinical practice and to seek approval
for its use under JHI.

Patients and Methods
The Health Insurance Committee of the JapaneseSociety of Pediatric Interventional Cardiology (JPIC)
conducted the survey and evaluated the eﬃcacy andsafety of the procedure. A well-structured, validated,
multiple response type questionnaire regarding DS
procedures performed during the three years between
April 1, 2013 and March 31, 2016 was sent to the JPIC
managers of all the 35 institutions in August, 2016; we
received the completed questionnaires from responding
institutions by October 31, 2016. The questionnaire contained 23 items including patient characteristics: age indays, gender, anthropomorphic data (weight and height)
at stenting, therapeutic indication, established medical
diagnosis, associated comorbidities, previous surgicalintervention, previous catheter intervention, use periodof prostaglandin E1 (PGE1) before stenting; stenting:size and configuration of AD, approach site, how todeliver and implant the stent, the kinds of stent, guidewire, and sheath, usage of other balloon to remount thestent, procedure achievement, complications, peripheral
oxygen saturation before and after stenting, flow velocity
measured by pulsed wave/continuous wave Doppler
before and after stenting; and outcome: withdrawal of
PGE1, and outcome (Table 1). Responses to the questionnaire were aggregated for analyses by December 31,
2016.
Statistical Analyses
All data are expressed as the mean values with standard deviation or median values with ranges. Student
t-test and chi-square test were performed for continuous
variables and categorical data, respectively. All the analyses were performed using SPSS software (SPSS, Chicago,
IL, USA). For two-tailed hypothesis, p<0.05 was considered to be statistically significant.

Results
We received the replies from 28 of the 35 institutions.
J Pediatr Cardiol Card Surg Vol. 3, No. 1 (2019)

Fig. 1 Ductal stenting for restoring systemic circulation performed at 12 institutions in Japanbetween April 1, 2013 and March 31, 2016

Of these, DS was performed in 64 cases at 12 institutionsin the three years. The purpose of DS was to maintainsystemic circulation in 62 cases and to do pulmonary
circulation in the remaining 2 cases. Therefore, we
describe DS performed for maintaining systemic circulation in these cases. The number of DS proceduresin each institution is shown in Fig. 1. The top three
institutions performed >10 procedures during the 3
years. Table 2 represents the characteristics of 62 patients
having undergone DS. Major indications for performing
DS were patients with a high risk for alternative surgery
such as Norwood or urgent stenting owing to the closureof AD despite of the use of PGE1; the percentage of DS
performed because of these indications was 82%. However, DS was also performed based on each institutional
principle (18%). In this setting, the patient does notalways have a high risk for the alternative procedure.
Patient diagnosis indicates that approximately 63% of
the patients exhibited univentricular physiology, andthe remaining had biventricular physiology. The medianage and weight of the patients at the time of DS were 21
days old and 2.8 kg. Bilateral pulmonary artery banding
was performed prior to DS in 38 cases (61%). Catheter
interventions were performed prior to DS in 15 cases(24%), which included balloon atrial septostomy in 10
cases with univentricular physiology, balloon aortic
valvuloplasty in 4 cases with critical aortic stenosis, andpulmonary artery band dilation in 1 case.
Table 3 shows characteristics of the ADs and the 62
implanted stents. The mean maximum diameter and3

Table 1 Survey of current state of ductal stenting in Japan
Survey items

AnswerExamples of items listed

Patient backgroundAt stenting
1 Year
2 Age
3 Gender4 Height
5 Weight
6 Therapeutic indication[year][day(s)]Select[cm][kg]
SelectSelect(Male, Female)(A) Restoring systemic circulation(B) Restoring pulmonary circulation(1) High risk of alternative
surgery(2) Institutinal principle(3) Ineﬀective PGE1/urgent
procedure(4) Others

Describe speciﬁcally in case (4)7 Diagnosis

Select(1) HLHS including its variant(2) PA·IVS(3) TOF/PA·VSD(4) Others

Describe speciﬁcally in case (4)8 Previous surgical intervention

9 Previous catheter intervention

10 Period of using prostglandin E1 before
stenting

MS AA PFO PDA; UVH CAVCDORV PA PDA
5 day-old, Bil.PA banding

Patinet age
and the procedure
Patinet age
and the procedure[days]

0 day-old, BAS

Stenting
11 Conﬁguration of arterial duct
Minimum lumen diameter×length
Reference vessel diamter (Ao end;
PA end)Pressure garadient before stenting
Pressure garadient after stenting
12 Approach site

[mm×mm][mm; mm][mmHg][mmHg]
SelectDescribe speciﬁcally in case (5) or (6)13 How to deliver and implant the stent
Select14 Implanted stentType

SelectName of the product
Size (dimater×length)[mm×mm](1) Hybrid (concommitant
procedure)(2) Femoral vein(3) Femoral artery(4) Juglar vein(5) Common carotid artery(inclusing cut down)(6) Other

Bil.PA banding; None

(1) Bare delivery(2) Bare delivery on a wire loop
(3) Back loading(4) (Including half way) frontloading(Balloon-expandable, Self-expandable)
Parmaz Genesis 1860; Precise
PRO RX
6 mm×18 mm© 2019 Japanese Society of Pediatric Cardiology and Cardiac Surgery

4

Table 1 Continued
Survey items
15 Use of other balloon to remount the
stent
Name of the balloon catheter in caseyes
Size (diameter×length) of it
16 Guidewire used
Name
Outside diameter
17 Sheath used
Name
Internal diameter
Length18 Procedure achievement

Answer
SelectSterling[mm×mm]

8 mm×20 mm
GrandSlam
0.014″[inch]

BriteTip
6 Fr
45 cm

[Fr]
Select(1) Success after implantationof 1 stent(2) Success after implantationof 2 stents(3) Failure

Describe the reason in case (3)Describe speciﬁcally if additional stenting was performed later date19 Complications

A Genesis stent (1560) was
additionaly implanted from theright femoral vein because thepulmonary end of the arterial duct
became narrow.
Select(Yes, No)The contents in case yes

Stent migration to the main
pulmonary artery; Hypotension,
which was recovered after epinephrin IV, etc.
The migrated stent was recaputured with a 8 mm×2 cm Saberballoon catheter and it was placeed at the target site.

How to deal with it

20 SpO2 before stenting
SpO2 after stenting
21 Flow velocity measured by PW/CW
before stenting
Flow velocity measured by PW/CW
after stenting

Examples of items listed(Yes, No)

[%]
[%]
[m/s]
[m/s]

Outcome22 Withdrawal of prostagrandin E1
23 Outcome
Whether or not did the patient reachthe next stage surgery?
What was the next stage surgery?

Select(Yes, No)
Norwood & BDG at 6 month ofage; Waiting for Norwood procedure; During follow-up; Sudden
death after discharged, etc

CW, continuous wave Doppler; PW, pulsed wave Doppler; SpO2, oxygen saturation of peripheral artery

length of ADs were approximately 6.5 mm and 13 mm.
The mean diameter and length of the stents were 7.4 mm
and 17.2 mm relative to the size of ADs. Most of thestents were balloon expandable, and the majority ofthem were the products of Express Vascular and Palmaz
Genesis. Table 4 shows how to deliver and place thestents, the results of them, and outcomes following stentimplantation. Twenty four DS were implanted by hybrid
procedure (39%), whereas the remaining were implanted
by percutaneous procedures (61%). For percutaneous
procedures, the predominant access site was the femoral
J Pediatr Cardiol Card Surg Vol. 3, No. 1 (2019)vein, and methods for stent delivery included back loading way, bare delivery, and venous-artery wire loop. All
the 62 procedures achieved 100% success rate, and PGE1
was withdrawn in 60 cases (97%). In the remaining twocases, the uncovered parts of ADs became constricted
after the withdrawal of PGE1, which was due to stentmigration toward the main pulmonary artery in one
case, and PGE1 was restarted until Norwood procedure was performed in one case, and Norwood andbidirectional Glenn procedure was performed in theother case. Major complications occurred in 10 cases

5

Table 2 Characteristics of the 62 cases having undergone ductal stenting
Indication for performing the DS
1. High risk of alternative surgery
2. Institutinal principle
3. Ineﬀective PGE1/urgent DS
4. 1 and 3

Number32
11
13
6

Arterial duct
51%
18%
21%
10%

Diagnosis
Hypoplastic left heart syndrome
Univentricular heart with CoA/AS
Critical AS
IAA/CoA with AS/SAS
Truncus with IAA
IAA and ventricular septal defectCardiac tumor
Details unknown in association
with 13/18 trisomy

median (range)
median (range)
Male : Female

Previeous surgery
Bil.PA banding
Bil.PA banding & ASD creation

21
2.8
28 : 34
38

15

Balloon atrial septostomy
Balloon aortic valvuroplasty
PA band dilation

1041

4.6±1.6
13.0±3.5
6.4±1.5
6.5±1.6
8.5±9.0

Diameter
Length

7.4±1.2
17.2±2.6
Stent products

Balloon expandable(2∼300)(1.8∼8.0)
61%

35
3

Previous catheter intervention

Minimum diameter
LengthAortic end diameter
Pulmonary end diameter
Pressure gradient

mm
mm
mm
mm
mmHg

Stent size

28
5
4
17
2
2
1
3

At stent implantation
Age [days]
Weight [kg]GenderTable 3 Characteristics of the arterial ducts andimplanted stents

24%

AS, aortic stenosis; ASD, atrial septal defect; Bil., bilateral;
CoA, coarctation of the aorta; DS, ductal stenting; IAA,
interrupted aortic arch; PA, pulmonary artery; PGE1, prostaglandin E1; SAS subaortic stenosis(16%). Stent migration or embolization occurred in 6
cases (9.7%). In 4 out of the 6 cases, stents migrated tothe main pulmonary artery, and in the other two, stents
migrated into the descending aorta. In 4 of these 6
cases, stents were correctly repositioned using a balloon
catheter, whereas in the remaining 2 cases, stents wereleft where the stent migrated. In one case of the 6 cases,
stent migration occurred following cardiac massage forrecurrent transient bradycardia. Except for this case,the mean diameter of the 5 stents which migrated was
only 0.04 mm larger than the mean maximum diameterof the ADs, whereas that of the 56 stents which did not
migrate was 0.93 mm larger than that. There was no statistically significant diﬀerence between the two groups.
Dissection was recognized in 3 cases (4.8%), including
AD, descending aorta, and main pulmonary artery. In 1of these 3 cases, dissection of the descending aorta wasrecovered by an additional stent. During the period fromDS to the next stage surgery, additional treatments were

mm
mm
(n)
58

Express Vascular LD
Express Vascular SD
Palmaz Genesis (large)
Palmaz Genesis (medium)
Omnilink Elite
Assurant Cobalt

25
5
8
15
4
1

Self expandable

4

Wall
Epic Vascular31also performed, which included additional stenting in 2
cases, stent redilation in other 2 cases, and continuationof PGE1 in the remaining 2 cases (described above).
There was no mortality associated with the proceduresor complications.
Outcomes of the 62 cases included Norwood andbidirectional Glenn procedure in 11 cases, Norwood
procedure in 20 cases, biventricular repair such as Yasui
procedure in 15 cases, waiting for the next stage surgery
in 11 cases, death from the underlying heart disease in
1 case, and death from other non-cardiac diseases in 4
cases. Except for the 11 cases waiting for the next stage
surgery, 46 of 51 cases reached the next stage surgery(90%).

Discussion
No study has directly compared outcomes between
primary Norwood and hybrid procedures in Norwood-high-risk neonates with HLHS in the same
institute. However, hospital mortality after primary
Norwood procedure for Norwood-high-risk neonateswith HLHS is approximately 45% in institutes where
the survival rates after primary Norwood procedure is>90%.3, 4) Whereas, in the institute in Giessen, where
primary hybrid procedure was performed most in theworld, hybrid procedure has been performed in all
neonates with HLHS since 1998, and the survival rate

© 2019 Japanese Society of Pediatric Cardiology and Cardiac Surgery

6

Table 4 How to implant the stents, the results andoutcome of the patients
Approach site
Main pulmonary artery by hybrid procedure
Femoral vein
Jugular vein
Femoral artery

(n)
24
35
2
1

38.7%

HybridBack loading
Bare dilevery
Venos-artery wire loop

24
19
10
9

38.7%

Procedure achievement

62

100%

Withdrawal of prostaglandin E1

60

96.7%

Complications at implantation

10

16.1%

How to deliver and implant

Death
Bradycardia
Stent migration/embolization
Repositioning with a balloon
Leaving it where the stent migrated
Dissection (arterial duct/descending aorta/
main pulmonary artery)
Stent addition
Observation
Additional treatments
Stent addition
Stent re-dilation
Restart of prostagrandin E1

0
1
6
4
2
3

9.7%

4.8%

1
2
6

9.7%

2
2
2

Outcome of the 62 cases
Norwood & bidirectional Glenn
Norwood
Biventricular repair
Waiting for the next stage surgery
Death from the undelying cardiac disease
Death from other non-cardiac diseases

11
20
15
11
1
4

at 5 year in Norwood-high-risk patients with HLHS is>80%.10) These results may indicate that hybrid procedure has better outcomes than Norwood procedure for
Norwood-high-risk neonates with HLHS in institutes
where these interventions are frequently performed.
The finding of this survey indicates that in the majority of institutes in Japan, DS for restoring systemic circulation is urgently needed and is usually performed using
oﬀ-label stents in approximately 20 patients per year,
who are presented with a serious congenital heart disease including HLHS, univentricular heart, and severe
subaortic stenosis with interrupted aortic arch. The indication for DS includes not only high risk of alternative
surgery such as Norwood operation particularly in neonates and/or crucial procedure due to the closure of the
AD in spite of using PGE1 but also based on own institutional principle. This indicates that in such institutes, a
J Pediatr Cardiol Card Surg Vol. 3, No. 1 (2019)hybrid approach comprising DS is performed as a basic
procedure in patients with standard risk for Norwood
procedure. The mean length and diameter of selected
stents in 62 cases were 17.2±2.6 mm and 7.4±1.2 mm
for the AD with a mean length and maximum diameterof 13.0±3.5 mm and 6.5±1.5 mm so that each stent
covered the whole arterial duct without migration. The
major complication associated with DS was stent migration or embolization. In this study, the mean diameterof the 5 stents which migrated was only 0.04 mm larger
than the mean maximum diameter of the ADs, whereasthat of the 56 stents which did not migrate was 0.93 mm
larger than that. To prevent stent migration, it was highly
recommended to select a stent with a diameter 1 to 2 mmlarger than the maximum AD diameter, although thisis in the case of self-expandable stents.11, 14) Although
self-expandable stents are primarily used in Europe
and North America, stent migration or embolization
was recognized with a frequency of 2.5%‒14%.9, 14) It isbelieved that this complication tends to occur during theearly period in the learning curve of the institutes.
Recently, Sinus-SuperFlex-DS stent with CE markfor ADs has been introduced for routine use in Europe.
Besides, this self-expandable stent is available in a variety of sizes and can be delivered with the 4 Fr. system.
This stent is specifically designed to accommodate thesoft curvature of the AD to facilitate physiological flow,
reduce complication rates, and allow easier surgicalremoval at the time of arch reconstruction.11) In contrast,
in Japan, balloon-expandable stents have been mainly
used for DS because there are hardly self-expandable
stents that fit into neonatal AD. Stents of Express Vascular and Palmaz Genesis are the most widely used becauseof their flexibility and variety of available sizes. Notably,in the case of accompanying coarctation of the aorta, DS
using side cell dilation is an eﬀective procedure. The Palmaz Genesis stent with a closed-cell design with interposed sigma hinges has an advantage to enable a side cellmore largely dilated over Express Vascular stent because
the former has a sigmoid structure of hinges of struts,
and the sigmoid parts are elongated into linear when theside cell was dilated with a balloon.12) The side cell dilation technique is particularly useful if a stent migrates
distally resulting in the stent covering the junction to theisthmus of the aortic arch.
To achieve long-term safety of DS, a balloon expandable stent and also a self-expandable stent with optimal

7

flexibility must be approved for use in AD because
the AD has various configurations including no waist,strongly constricted, large and long, and accompanying coarctation of the aorta; furthermore, circulation
becomes easily worsened, especially when hard materials are used in neonates with univentricular physiology.

Conclusion
In Japan, DS for restoring systemic circulation isneeded in patients with severe congenital heart disease
including HLHS, univentricular heart, and subaortic
stenosis with interrupted aortic arch. The present study
strongly recommends that both balloon-expandable
stent and self-expandable stent must be approved for thesafe and eﬃcient intervention of AD under JHI as soon
as possible.
Acknowledgment
We thank the JPIC managers who cooperated on thissurvey in the 28 institutions; Sakakibara Heart Institute,
National Center for Child Health and Development, The
University of Tokyo Hospital, Tokyo Metropolitan Childrenʼs Medical Center, Toho University Omori Medical
Center, Toho University Ohashi Medical Center, Showa
University Northern Yokohama Hospital CardiovascularCenter, Shizuoka Childrenʼs Hospital, Seirei Hamamatsu
General Hospital, Chukyo Hospital, Mie University Hospital, National Cerebral and Cardiovascular Center, Osaka
City General Hospital, Osaka Womenʼs and Childrenʼs
Hospital, Hyogo Prefectural Kobe Childrenʼs Hospital,
Okayama University Hospital, Kurashiki Central Hospital,
Hiroshima City Hiroshima Citizens Hospital, Shimane
University, Tokushima University, Fukuoka Childrenʼs Hospital, Kyushu Hospital, Okinawa Prefectural Nanbu Medical
Center.
Conﬂicts of Interest
The authors have no financial conflicts of interest to disclose concerning this study or the manuscript.

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