Journal of Pediatric Cardiology and Cardiac Surgery 8(2): 70‒76 (2024)

Case Report

An Integrated Treatment for Isolated Partial Anomalous Pulmonary
Venous Connection with Severe Pulmonary Hypertension
Hiroki Wakamatsu, MD, PhD1), Hirono Satokawa, MD, PhD1), Emi Nagata, MD1),
Hitoshi Yokoyama, MD, PhD1), Nobuo Momoi, MD, PhD2), Yoshimichi Aoyagi, MD, PhD2),
Mariko Hayashi, MD2), and Kazuhiko Nakazato, MD, PhD3)
1) Department of Cardiovascular Surgery, Fukushima Medical University, Fukushima, Japan
2) Department of Pediatrics, Fukushima Medical University, Fukushima, Japan

3) Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, JapanThe optimal treatment for unrepaired congenital heart disease in adults with pulmonary arterial hypertension(PAH) has not yet been clarified. We here report a case of a 42-year-old man who underwent successful surgicalrepair of isolated partial anomalous pulmonary venous connection (PAPVC) following target therapy for PAH.
He presented with progressive exertional dyspnea. Enhanced computed tomography showed the right upper andmiddle pulmonary veins draining into the superior vena cava (SVC). Right heart catheterization showed thatmean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) were 91 mmHg and 20.3
Wood unit, respectively. He was subsequently treated with three specific PAH drugs (macitentan, tadalafil andselexipag) for 9 months. Follow-up catheterization showed that his mean PAP and PVR decreased to 45 mmHg
and 2.7 Wood unit, respectively. Side effects of the PAH specific drugs, however, eventually caused poor medication adherence. As interruption of these drugs was likely to cause re-progression of PAH, the patient underwent
surgical repair. The anomalous pulmonary veins were redirected into the left atrium through a surgically createdatrial septal defect. The SVC was divided and reconstructed using a right atrial wall flap and an autologous pericardial patch. His exercise tolerance and PAH gradually improved thereafter. Catheter examination 15 months
after surgery showed mean PAP was 34 mmHg. Specific target therapy for PAH could improve severe PAH related
to isolated PAPVC in adults patients, and could make management of their circumstances easy and safe during
the perioperative period.

Keywords: adult congenital heart disease, isolated partial anomalous pulmonary venous connection,
pulmonary arterial hypertension with congenital heart disease, modified Warden method, cardiac surgery

Introduction
Isolated partial anomalous pulmonary venous connection (PAPVC) has no intra-cardiac malformation,such as atrial septal defect (ASD). It is rare, and if left
unrepaired, pulmonary arterial hypertension (PAH)
could develop during adulthood. Recent reports haveshown that congenital heart diseases (CHD) with PAH
are amenable to successful surgical repair after appro-

priate target therapy for PAH even in adults. Still, such atherapeutic strategy remains unclear for isolated PAPVC
presenting PAH. We herein report an adult patient
whose isolated PAPVC was successfully repaired following administration of specific drugs for PAH.

Case Presentation
A 42-year-old man was referred to our hospital
because of fatigue and exertional dyspnea; he often

Received: April 19, 2023; Accepted: September 13, 2023
J-STAGE Advance Published Online: July 9, 2024
Corresponding author: Hiroki Wakamatsu, MD, PhD, Department of Cardiovascular Surgery, Fukushima Medical University,
Fukushima 960‒1295, Japan
E-mail: h-waka@fmu.ac.jp
Hiroki Wakamatsu ( https://orcid.org/0009-0001-7689-0949)
doi: 10.24509/jpccs.23-007© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery
This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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Fig. 1 Preoperative chest X-ray (A) and electrocardiogram (B)CTR, cardio-thoracic ratio.

Fig. 2 Preoperative transthoracic echocardiogram
The short axis view shows left ventricular deformity due to right ventricular dilatation (A). Doppler measurement of tricuspid
regurgitation indicates high right ventricular pressure (B). LV, left ventricle; RV, right ventricle.

complained dyspnea when going up stairs. The causeof fatigue and dyspnea had not been detected, although
he visited multiple clinics and his chest radiography at
medical checkup already showed dilatation of the bilateral pulmonary arteries (Fig. 1A). He was unable to go
to work due to his symptoms. On physical examination,
his blood pressure and pulse rate were 114/86 mmHg
and 78 bpm, respectively. He had a regular rhythm
and a respiratory rate of 12 bpm with a percutaneous
oxygen saturation of 98% in room air. His second heartsound was accentuated, and no heart murmur audible.
A 6-minute walk distance was 390 m. These findings
suggested that he was classified into New York Heart

Association (NYHA) functional class III. Electrocardiography showed regular sinus rhythm, axis deviation
and right ventricular hypertrophy with complete rightbundle branch block (Fig. 1B). Echocardiography
showed enlargement of the right ventricle and flatteningof the interventricular septum. Doppler measurementof tricuspid regurgitation revealed that estimated rightventricular pressure was 103.1 mmHg (Fig. 2A, B).
Contrast-enhanced computed tomography illustrated
that the right upper and middle pulmonary veins (PVs)drained into the SVC, and that the pulmonary arteries
as well as the right ventricle were dilated. Additionally,
these anomalous PVs had been shifted upward due© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery

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Fig. 3 Preoperative computed tomography
The right upper and middle pulmonary veins were connected to the superior vena cava on angiograms (A, B). Coronal andsagittal views (C, D, E) also showed right partial anomalous pulmonary venous return into the superior vena cava. White
arrows: anomalous pulmonary veins, *: the superior vena cava, **: the right atrium.

Table 1 Consecutive catheter data and use of agents treating pulmonary arterial hypertension
RA a/v (mmHg)
RV (mmHg)
PA (mmHg)
Pcwp (mmHg)
LV (mmHg)
Ao (mmHg)
PVR (WU)
Qp/Qs

on admission

6 months later

9 months later

after surgery

15/14
125/EDP 14
126/69 (91)
13/13 (12)146/EDP 11
145/109 (126)
20.3
1.4

8/6 (5)64/EDP 2
69/39 (49)
8/9 (7)
149/EDP 4
135/82 (107)8.6
2.0

12/9 (8)65/EDP 10
64/30 (45)21/19 (15)

13/10 (9)46/EDP 5
46/26 (34)
20/18 (15)

̶
̶

2.7
3.2

̶
̶
̶
̶

̶
̶
̶

40
10
0.4 → 0.8 → 3.2

40
10
3.2

40
10
3.2

PAH speciﬁc drugs
Tadalaﬁl (mg)
Macitentan (mg)Selexipag (mg)Ao, aorta; EDP, end diastolic pressure; LV, left ventricle; PA, pulmonary artery; Pcwp, pulmonary capillary wedge pressure; PVR,
pulmonary vascular resistance; Qp/Qs, pulmonary to systemic blood ﬂow ratio; RA, right atrium; RV, right ventricle; WU, Wood unit.

to the dilated right pulmonary artery (Fig. 3). During
this investigation, the patient suddenly collapsed withlow blood pressure, and immediate cardiopulmonary
resuscitation was needed. Probably, PAH deteriorated
subsequent to injection of contrast media, causing
acute volume overload and an increase in pulmonary
vascular resistance. Right heart catheterization (RHC)
eventually revealed the systemic to pulmonary bloodflow ratio (Qp/Qs) 1.4, mean pulmonary arterial pressure (PAP) 91 mmHg, pulmonary capillary wedge
pressure 12 mmHg, and pulmonary vascular resistance
J Pediatr Cardiol Card Surg Vol. 8, No. 2 (2024)(PVR) 20.3 WU, respectively (Table 1). Acute vasodilator test using the combination of inhaled oxygen andnitric oxide (iNO) showed PAP and PVR remaining
unchanged. PAH related with heredity, drugs and left
ventricular dysfunction, respiratory diseases were ruledout after PAH workup. Consequently, we started a combined therapy using PAH-specific drugs. Macitentan(20 mg/day) and tadalafil (10 mg/day) were immediately
administered after the RHC. In addition, selexipag was
gradually increased from 2 to 10 mg/day at our outpatient clinic. The second RHC took place 6 months after

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Fig. 4 Operative ﬁndings(A) An inter-atrial communication was created at the oval fossa (*). Dotted arrows indicate incision lines to design an
atrial wall ﬂap. (B) A polytetraﬂuoroethylene patch was used for intra-atrial rerouting (**). (C) The superior vena cava wasreconstructed using an atrial wall ﬂap for the posterior side and a fresh autologous pericardium patch (***) for the anterior
side. (D) Reconstruction of the superior vena cava completed. PA, pulmonary artery; PAPVC, partial anomalous pulmonary
venous connection; RA, right atrium, SVC, superior vena cava.

introduction of the PAH drugs, measuring mean PAP
49 mmHg (69/39 mmHg) and PVR 8.6 WU. The Qp/Qs
ratio had increased to 2.0 (Table 1). The third RHC
was carried out 9 months after initiation of the PAH
drugs; mean PAP 45 mmHg (64/30 mmHg), which was
similar to the value at the second RHC. Furthermore,
PVR markedly improved (down to 2.7 WU), and the
Qp/Qs ratio increased (up to 3.2) (Table 1). The patientʼs
exercise tolerance became better thereafter as his PAH
improved. On the other hand, side effects of the PAH
drugs, such as diarrhea and headache, gradually resulted
in poor medication adherence. As interruption of PAH
drugs likely results in progressive PAH, we decided torecommend surgical repair.
Operative Findings
Surgery was carried out through a median sternotomy. At first, the superior vena cava (SVC) was extensively dissected, and then cardiopulmonary bypass wasestablished inserting cannulae into the ascending aorta
and the caval veins. The cannula into the SVC was placed
as high as possible distant from the right atrium (RA),and a venting tube was inserted into the main pulmonary trunk. The SVC was divided just above the rightanomalous PVs, and the proximal stump of the SVC was
directly closed. The RA appendage could not be mobilized to the distal end of the SVC for direct anastomosis,
because the RA appendage was less flexible due to severe

RA dilatation and thickening of its wall. There was a
distance of 4 cm between the distal stump of the SVC
and the RA appendage (Fig. 4A). After inducing cardiac
arrest, the RA was incised. The atrial septum was incisedat the fossa ovalis, and an ASD, approximately a diameter of 15 mm, was created surgically (Fig. 4A). The edgeof the created ASD was sewed carefully by means of theso-called intima-to-intima suturing in order to maintaincontinuation of the endocardial surface (Fig. 4A). The
right anomalous PVs were rerouted into the left atrium
through the ASD using an extended polytetrafluoroethylene prosthetic patch (Fig. 4B). After releasing the aortic clamp, heart rhythm recovered in sinus rhythm. The
posterior wall of a neo-SVC channel was reconstructedusing an atrial wall flap that was created from the anterior wall of the RA. The anterior wall of the neo-SVC wasaugmented using a fresh autologous pericardial patch(Fig. 4B, C, D). Weaning from cardiopulmonary bypass
was successful with iNO. Arterial blood pressure was
83/51 mmHg, and PAP was 38/23 mmHg. The durationsof the operation, cardiopulmonary bypass, and aortic
cross-clamp were 260, 149, and 68 minutes, respectively.
Postoperative Course
The PAH drugs were resumed, in the same doses as
preoperatively administered, via a gastric tube from thefirst postoperative day. After iNO ceased, the patient
was weaned off mechanical ventilation on the second© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery

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Fig. 5 Postoperative computed tomography
Angiograms (A, B) show the right upper and middle pulmonary veins redirected into the superior vena cava. The intra-atrial
patch (*) divides the region into the right atrial cavity (**) and the pulmonary venous channel. Coronal and sagittal views (C,D) also show the separate routes for the pulmonary veins and the superior vena cava draining into the right atrial cavity (**).
PV, pulmonary venous; SVC, superior vena cava.

postoperative day. On the following day, oral intake wasrestarted, and oral warfarin was prescribed for anticoagulation therapy. Inotropic support was gradually
decreased and stopped on the 5th postoperative day.
On the 6th postoperative day, nasal oxygen cannula
was removed, and he was discharged from the intensive
care unit to a general ward. Postoperative enhanced CT
revealed that the neo-SVC and the PV routes had no
obstruction (Fig. 5). Electrocardiogram showed sinus
rhythm. Transthoracic echocardiography suggested thatblood flows across the right PVs and the SVC had been
well established, and that PAH had improved (Fig. 6),
Thereby the patient was discharged home on the 16th
postoperative day. His clinical status improved to NYHA
functional class I. He returned to his work at 2 months
after surgery. The dosage of selexipag was graduallyweaned according to the echocardiographic findings.
We performed RHC at 15 months after surgery, whichshowed that mean PAP decreased to 34 mmHg. Macitentan and tadalafil were continued although selexipag
was changed to beraprost due to adverse effects such as
diarrhea and face flushing.

J Pediatr Cardiol Card Surg Vol. 8, No. 2 (2024)

Fig. 6 Postoperative transthoracic echocardiogram
The left ventricle is less deformed in the short axis
view. LV, left ventricle; RV, right ventricle.

Discussion
Pathophysiology of PAH in Adults With Isolated
PAPVC
The most common type of PAPVC is a right upper
PV draining to the SVC, followed by the right PVs
directly to the RA or the left PV to the left innominate
vein.1) It is not yet clear which types of PAPVC tend
to lead to PAH, since this malformation is relatively rareand data regarding the PAH is limited. Isolated PAPVC

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is a quite unusual form of CHD1, 2) that could cause
PAH in adults.3) Majadalary et al.4) reported patientswith two or more anomalous PVs were likely to haveright ventricular enlargement requiring intervention.
Some patients develop severe PAH even with a solitaryanomalous PV, since the amount of anomalous venous
flow in isolated PAPVC directly overload the amountof pulmonary arterial flow. Therefore, we need to follow
carefully the clinical course in patients with isolated
PAPVC regardless of the number of abnormal PVs.
Assessment and Treatment for CHD With PAH
A patient with CHD and PAH should undergo surgical treatment when pulmonary vascular resistance islow, particularly below 3 WU.5) In contrast, a therapeuticstrategy in adults with isolated PAPVC and significant
PAH remains unclear. In our patient, initial PVR was
extremely high (over 20 WU). With this finding, it
was judged that repair of an intra-cardiac shunt was
infeasible based on the guidelines for adult ASD closure by European Society of Cardiology and European
Respiratory Society (ESC/ERS).5) Closure of a shunt
across an ASD may be indicated when PVR 5 WU orgreater declines to less than 5 WU with PAH treatment
as far as ordinary ASD physiology is concerned. In
our present patient, testing for acute vaso-reactivity
with iNO showed negative response. We challenged
further to assess reversibility and operability afterusing multi-pathway medication (Endothelin, NO or
Prostacyclin) with a wish for improvement. We therefore readily proceeded to upfront combination therapy
with three classes of specific PAH medication. Overthe course of the PAH therapy, the patientʼs cardiac
output gradually increased with PVR decreasing, andhis exercise tolerance significantly improved. In recent
years, the so-called “treat-and-repair strategy” has been
attracting attention as a brand-new approach.6) Closureof intra-cardiac shunts is to be established after PAH
control using specific drugs for CHD with PAH. There
are only a few reports about “treat and repair technique”
for isolated PAPVC with severe PAH.6‒8) As for adult
ASD patients with PAH, some criteria have been proposed in Japan based on clinical results of PAH treatment using multiple medications. Kijima et al.7) reported
that the criteria for percutaneous ASD closure would be
PVR <8 WU and Qp/Qs ≥1.5 after PAH treatment.
Yao et al.8) suggested that the criteria for managing ASD

closure should be a PVR of <7.5 WU, a Qp/Qs of >1.5,
and right ventricular ejection fraction of >0.4 after PAH
treatment. These criteria were based on studies witha relatively small cohort, and details of postoperative
administration of PAH drugs remained unclear. In our
PAPVC patient, the RHC 9 months after initiation of
upfront combination therapy revealed a drastic decreaseof PVR (down to 2.7 WU). Without a radical repair, thepatientʼs PAH could return to a difficult circumstancebecause of poor medication adherence due to adverse
effects. We were concerned about it. This was the reason
we concluded that his intra-cardiac shunt should be
repaired on the basis of the above-mentioned criteria
for ASD closure. We discussed whether leaving a small
ASD fenestration would be necessary; the hole could
have acted as a safety-valve for postoperative PAH crisis.
We decided, nonetheless, not to provide such a residual
communication; we regarded it unnecessary considering
his low PVR.
Surgical Technique for Isolated PAPVC
A couple of crucial points at surgery for PAPVC repair
are how to protect sinus nodal function and how toprevent obstruction across the SVC and the PV routes.
The surgical procedures are affected by how high theanomalous PVs are connected to the SVC, how large thediameter of the SVC is, and how large the volume of the
RA is. Said et al.9) recommended the use of the Warden
procedure with superior caval division for PAPVC repair
when an anomalous PV drained into the SVC morethan 1 cm above the cavo-atrial junction. When direct
anastomosis turned out to be difficult between the distal
stump of the SVC and the RA appendage, a Gore-Tex
tube graft was interposed as a modified Warden procedure. We suggest that the caval division technique
should be accompanied with adequate mobilization of
the cephalad part of the SVC and the RA appendage.
The anomalous PV connection could have been shifted
upward due to dilatation of the right PA. In our patient,
the anomalous PVs drained into a quite distal segmentof the SVC (Fig. 4A). We therefore chose the caval division procedure. As described above, a flap made of theanterior wall of the RA was used for reconstructing theposterior wall of the new SVC channel.10) The anteriorwall of the channel was augmented using a fresh autologous pericardial patch. Thus, the new SVC pathway
is surrounded by autologous tissues. These maneuvers© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery

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were carried out after intra-atrial rerouting, evaluating
the distance between the distal stump of the divided
SVC and the RA, and creating a suitable size of the RA
wall flap after removal of the aortic cross-clamp. This is a
useful alternative surgical method to treat adult patients
whose anomalous PVs returns high of the SVC. In addition, this method was safer and technically easier thanother previous techniques. Both routes continued toprovide smooth flows at the 1-year follow up.
Diagnosis of CHD in Adulthood
Idiopathic PAH diagnosed in adulthood might include
operable CHD once PAH is controlled using specificdrugs. Thus, CHD should be sought in adult cases with
idiopathic PAH, and PAH treatment should be initiatedpromptly after the diagnosis. The contrast-enhanced
CT is useful for diagnosing PV anomalies,2) but use ofcontrast media in CHD patients with PAH might worsen
the degree of PAH. Especially, such an adverse effect ina CHD patient without intra-cardiac shunt is similar tothat in idiopathic PAH patients. The contrast-enhanced
CT should be performed after meticulous explanation
about the risk of reactive PAH inducing cardiogenic
shock in patients with severe PAH. In addition, PAH
treatment should be continuously administered forpotential PAH after surgery. In patients with PAH after
repair, PAH could be either still present immediately
after repair of an intra-cardiac shunt or could re-deteriorate several months or years after the procedure.11) Integrated treatments consisting of preoperative PAH treatment, intra-cardiac repair and postoperative remedy forresidual PAH might contribute to improving the qualityof life in the group of CHD with PAH. Unfortunately, it
was unable to identify surgical criteria or evidences forthis approach in prospective studies previously reported
for unrepaired adult patients with CHD, PAH andintra-cardiac shunts due to a limited patientsʼ population. In this regard, the accumulation of relevant data on
treatments for PAH in adult CHD patients would serve
to establish new guidelines. Further studies are required
to investigate the long-term results after PAPVC repair
in adulthood.

J Pediatr Cardiol Card Surg Vol. 8, No. 2 (2024)

Conﬂicts of Interest
None of authors have a conflict of interest.
Author Contribution
Hirono Satokawa, Emi Nagata and Hitoshi Yokoyama
contributed to the planning and treatment of the surgical procedure. Nobuo Momoi, Yoshimichi Aoyagi andMariko Hayashi were involved in perioperative hemodynamic assessment. Kazuhiko nakazato was involved in thepatientʼs PAH treatment plan. All authors reviewed themanuscript and approved final manuscript for publication.

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