Journal of Pediatric Cardiology and Cardiac Surgery 3(1): 39‒43 (2019)

Case Report

Implantation of Drug-Eluting Stent in the Vertical Vein ofa Patient with Obstructed Total Anomalous Pulmonary
Venous Connection Associated with Right Atrial Isomerism
Shin Ono, MD1), Hideaki Ueda, MD1), Ki-sung Kim, PhD1), and Toshihide Asou, PhD2)
1) Department of Pediatric Cardiology, Kanagawa Childrenʼs Medical Center, Yokohama, Japan

2) Department of Cardiovascular Surgery, Kanagawa Childrenʼs Medical Center, Yokohama, Japan

The prognosis in cases of right atrial isomerism with obstructed total anomalous pulmonary venous connection
remains unsatisfactory. In particular, mortality following surgical repair of obstructed total anomalous pulmonary venous connection in the neonatal period is high. This case report describes a patient who underwent primary drug-eluting stent implantation for treatment of obstructed total anomalous pulmonary venous connection
associated with right atrial isomerism. The stent was placed on the day of birth, and a definitive Fontan procedure
was performed at 16 months of age. We also discuss the stent specimen, which had been implanted in the verticalvein for a total of 5 months. To our knowledge, this case report is the first to describe a drug-eluting stent specimen implanted in a draining vein associated with right atrial isomerism.

Keywords: right atrial isomerism, asplenia, pulmonary venous obstruction, Fontan procedure,drug-eluting stentIntroduction
The surgical outcomes of patients with functional
single ventricles have improved during the last several
decades. However, the prognosis in cases of right atrial
isomerism (RAI) remains unsatisfactory.1) Draining veinstenosis in the context of total anomalous pulmonary
venous connection (TAPVC) is a substantial risk factor
for a poor outcome; however, several other factors also
likely contribute to an unfavorable prognosis, such as
ventricular dysfunction, significant arrhythmias, significant common atrioventricular valvular regurgitation,
obstruction of pulmonary outflow, and sepsis associated with splenic dysfunction.1) A recent multicenter
study demonstrated that TAPVC repair in patients withheterotaxy and a functional single ventricle has a highmortality rate of 43%.2) Another study showed that themortality rate following surgical repair of obstructed
TAPVC in the neonatal period is high.3) Stent implan-tation for obstructed TAPVC can forestall the need forsurgery in the neonatal period. However, the frequency
of in-stent stenosis is high, especially when a bare metal
stents (BMS) is used.4) In the present case, we implanted
a drug-eluting stent (DES) to bridge a vertical vein(VV) stenosis in a patient with supracardiac TAPVC
associated with RAI on the day of birth. We performeda successful Fontan procedure when the patient was 16months old. We also discuss the stent specimen, which
had been implanted in the VV for a total of 5 months.

Case Report
A prenatally diagnosed male infant was delivered byscheduled cesarean section at 37 weeks of gestation. His
birth weight was 2.6 kg. His respiration rate ranged from60 to 70 breaths/min, and his oxygen saturation ranged
from 50% to 60%. He was immediately intubated. Echocardiography revealed the same findings obtained in thefetal diagnosis: RAI, single right ventricle, single atrium,Received: August 3, 2018; Accepted: December 17, 2018
Corresponding author: Shin Ono, MD, Department of Pediatric Cardiology, Kanagawa Childrenʼs Medical Center, 2‒138‒4 Mutsukawa, Minami-ku, Yokohama, Kanagawa 232-8555, Japan
E-mail: sono@kcmc.jp
doi: 10.24509/jpccs.190107© 2019 Japanese Society of Pediatric Cardiology and Cardiac Surgery

40Fig. 1 Chest radiograph revealing a small cardiac
silhouette (cardiothoracic ratio of 47%) andpulmonary congestioncommon atrioventricular valve, right aortic arch, patentductus arteriosus, bilateral superior vena cava (SVC),and supracardiac TAPVC draining into the right-sided
SVC via a severely obstructed VV. A chest radiographrevealed a small cardiac silhouette (cardiothoracic ratioof 47%) and pulmonary congestion (Fig. 1). We decided
to place a palliative DES in the stenotic VV as planned
from the fetal period.
Three hours after birth, the patient was placed undergeneral anesthesia. First, we introduced a 5-Fr shortsheath into the right femoral vein. Using a 0.018-inch
Radifocus guide wire and a 4-Fr Judkins coronary rightcatheter, we delivered a 2.3-Fr Progreat microcatheter
to the common pulmonary venous chamber (CC).
The mean CC pressure was 21 mmHg. An angiogram
revealed severe stenosis of the VV (Fig. 2a). Next, wereplaced the short sheath with a 5-Fr Cook long sheath
and advanced it to the orifice of the VV draining into
the right SVC. Using a 0.018-inch Radifocus guide wire,a 2.3-Fr Progreat microcatheter, and a 4-Fr Judkins
coronary right catheter, we placed the distal side of the5-Fr Cook long sheath across the stenosis. Using the5-Fr Cook long sheath and a 0.014-inch Asahi Grand
Slam wire, we implanted a DES (Resolute Integrity™
4.0×9.0 mm) (Fig. 2b). The patientʼs oxygen saturationconsequently improved from 75% to 85% at a 0.21 fraction of inspired oxygen.
The patientʼs pulmonary blood flow increased daily,likely because of spontaneous reduction of pulmonary
J Pediatr Cardiol Card Surg Vol. 3, No. 1 (2019)

Fig. 2 Angiogram displaying anteroposterior viewsof the obstructed vertical vein (a) prior to and(b) after stent implantation. (c) Patent verticalvein 4 months after stent implantation. Contrast medium injected into the right superior
vena cava ﬂowed into the CC via the verticalvein (arrow).
CC: common pulmonary venous chamber

41

vascular resistance. At 4 days of age, we performed pulmonary artery (PA) banding (circumference diameter,17 mm) and ductal artery ligation. We administeredaspirin, warfarin, and heparin to maintain stent patency.
The patient grew steadily without apparent symptoms ofpulmonary venous obstruction.
At 33 days of age, we performed a diagnostic catheter examination. The pressure gradient across the stent
was 0 mmHg. Patency of the stent was confirmed by anangiogram. The mean PA pressure was 26 mmHg, which
exceeded the level at which the patient would have beena candidate for the Glenn procedure.
At 2 months of age, we performed TAPVC repair
and tightening of PA banding (circumference diameter,15 mm) instead of the Glenn procedure. The stent wasleft in place because removal would have been complicated. We discontinued antiplatelet and anticoagulation
therapy.
At 4 months of age, we performed another diagnostic catheter examination. The mean PA pressure was15 mmHg. The pulmonary blood flow/systemic bloodflow ratio and pulmonary resistance index were 2.3 and2.3 units×m2, respectively. These values were suitableto proceed with planning for the Glenn procedure. An
angiogram revealed that the stent remained widely patent (Fig. 2c). The diameter of the stent was 3.4 mm on theangiogram. Blood flow was detected from the SVC to theCC. The SVC pressure was 5 mmHg and the right atrial
pressure was 3 mmHg, suggesting that the pressure gradient across the stent was 2 mmHg. At 5 months of age,
we performed a bilateral bidirectional Glenn procedureand removed the stent. We discharged the patient 9 days
following the procedure. Fig. 3 shows the specimen ofthe stent. The stented lumen was widely patent without
stenosis or thrombosis. The configuration of the stent
was fully circular. The neointimal thickness was approximately 500 µm. The minimum inner diameter of thestent was 3.8×1.9 mm. The stent strut was completely
covered with the neointima. Chronic inflammatory cells,
including lymphocytes, histiocytes, and neovessels, wereobserved around the struts.
At 15 months of age, we performed embolization of
the aortopulmonary collateral arteries. We embolized
five vessels using an Amplatzer vascular plug 4 and Orbit
Galaxy detachable coils.
Two weeks later, we performed another catheter
examination. The mean PA pressure was 11 mmHg. TheFig. 3 Patent vessel wall of vertical vein with mild
neointima formation after stent implantation(a) The stented lumen was widely patent without
stenosis or thrombosis. The conﬁguration of thestent was fully circular. The neointimal thickness wasapproximately 500 µm. The minimum inner diameter of the stent was 3.8×1.9 mm. The stent strut
was completely covered by neointima. (b) Chronic
inﬂammatory cells including (a) lymphocytes, (b)histiocytes, and (c) neovessels were observed aroundthe struts.

pulmonary blood flow/systemic blood flow ratio and thepulmonary resistance index were 1.2 and 0.94 units×m2,respectively. The right ventricular ejection fraction was56%. Cardiac ventriculography revealed mild atrioventricular valve regurgitation. These values suggested thatthe patient was now a good candidate for the Fontan
procedure.
We performed the procedure when the patient was 16
months old using a 16-mm Gore-Tex extracardiac graft.
We extubated him 7 hours after surgery and discharged© 2019 Japanese Society of Pediatric Cardiology and Cardiac Surgery

42

him to home on postoperative day 10. The patient developed no adverse eﬀects of zotarolimus, which was eluted
from the Resolute Integrity™, such as cytopenia or renal
dysfunction.

Discussion
Neonatal surgical outcomes are poor for repair ofobstructed TAPVC associated with RAI.3) Recent evidence suggests that stenting of obstructed drainage veins
may improve outcomes by forestalling surgery during
the neonatal period.3) Unfortunately, in-stent stenosis
occurs frequently, especially when a BMS is used.4)
Considering the problem of restenosis of the pulmonaryveins, less in-stent stenosis may occur in stents witha diameter of ≥7 mm.5) However, evidence regarding
in-stent stenosis in the draining vein is lacking. Kitano
et al.6) showed good outcomes in such cases by repeated
redilation for in-stent stenosis. Some reports havedescribed implantation of a DES for obstructed TAPVC
with RAI.7) However, those reports did not mention
whether the patients eventually underwent successful
Fontan procedures.
A DES is designed for adult ischemic heart disease.
Restenosis rates are lower than those associated witha BMS.8) The Resolute Integrity™ elutes zotarolimus, asynthetic analog of rapamycin that is known to suppress
lymphocyte-mediated inflammation and neointimal
growth. The BioLinx polymer incorporated in the DES
improves biocompatibility and extends drug elution
for as long as 180 days, eﬀectively reducing neointimal
proliferation9, 10). The stent also features a new flexible
platform constructed from a cobalt-chromium alloythat increases deliverability and conformability.11) Thesefeatures allowed us to more easily deliver the stent to adraining vein with a complex shape. Clinicians shouldclosely observe patients for the development of systemic
adverse eﬀects of eluted drugs. Although some past studies showed no adverse events and a rapid decrease in theserum drug level after implantation of a DES, these studies did not evaluate zotarolimus-eluting stents12, 13). Ourpatient developed no adverse eﬀects, such as cytopenia
or renal dysfunction; however, we did not monitor theserum drug level.
Fig. 3 shows a stained section of the stent that had
been implanted in the VV 5 months prior. The lumen
was widely patent without evidence of stenosis orthrombosis. The configuration was fully circular, withJ Pediatr Cardiol Card Surg Vol. 3, No. 1 (2019)a neointimal thickness of approximately 500 µm. We
observed inflammatory cells surrounding the struts, but
not occupying the entire circumference. According to a
study of porcine coronary arteries, this form of inflammation would be grade 2 (on a scale of 0‒3).14) Whether
this scoring system can be generalized to human veinsis unknown. Because there is no similar pathologicalreport of BMS implanted in a drainage vein, we cannot
compare the pathological features between a DES andBMS.
The main disadvantage of a DES is its small diameter. The diameter of the Resolute Integrity™ is 4 mm.
This size may become insuﬃcient to receive pulmonary venous flow as the patient grows. Nakano et al.15)
successfully overdilated a Resolute Integrity™ with a
7-mm balloon in vitro; however, residual local stenosis
remained after attempting redilation with a 6-mm balloon in vivo. Although choosing a DES does not provide
a long asymptomatic period until the following surgery,
we believe that this stent size is adequate for use during
the neonatal period.

Conclusions
Implantation of a DES for obstructed drainage veinsis a palliative procedure that can forestall the need forthe first open heart surgery from one to several months.
To reduce mortality, it is desirable to delay open heart
surgery during the neonatal period whenever possible.3)
For critically ill neonates with RAI and obstructed
TAPVC, stenting of the stenotic draining vein of TAPVC
with a DES is an attractive option.
Acknowledgment
We thank Dr. Gaku Nakazawa for preparing the stentspecimens and for providing helpful insights. We also thankRobert Lindeman, MD, PhD and Angela Morben, DVM,
ELS from Edanz Group (www.edanzediting.com/ac) for
editing a draft of this manuscript.
Conﬂicts of Interest
The authors have no competing interests to disclose.

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