doi: 10.2169/internalmedicine.

7888-21
Intern Med 61: 851-855, 2022
http://internmed.jp

【 CASE REPORT 】

Clinical Outcome of Closure of a Small Atrial Septal Defect

in a Patient with Pulmonary Arterial Hypertension

Masahiko Umei 1, Akihito Saito 1, Katsura Soma 1, Toshiro Inaba 1, Masae Uehara 1,
Issei Komuro 1 and Atsushi Yao 2

Abstract:
The closure of small/coincidental atrial septal defects (ASDs) in patients with pulmonary arterial hyperten-
sion (PAH) has been described in recent major guidelines as useless or even contraindicated. We confirm the
effectiveness of “Treat and Repair” for ASD closure through one patient diagnosed with idiopathic PAH with
small ASD, under careful observation with right heart catheterization and cardiac magnetic resonance imag-
ing. The clinical decision concerning the closure of ASD with PAH should be made not only by referring to
the guidelines but also by evaluating the benefits and risks specific to that case.

Key words: atrial septal defect, pulmonary hypertension, percutaneous ASD closure

(Intern Med 61: 851-855, 2022)

(DOI: 10.2169/internalmedicine.7888-21)

of RV volume overload.
Introduction The guidelines for ACHD also state that, in the absence
of significant PH, ASDs that cause RV volume overload
Atrial septal defects (ASDs), accounting for approxi- should be closed at any age, even if they are relatively
mately 10% of all congenital heart disease, can result in pul- small, to prevent the development of RV failure or its pro-
monary hypertension (PH), right heart decompensation, gression. When deciding whether or not to close the ASD
atrial arrhythmias, and paradoxical embolism. Current guide- for patients with PAH with a small/coincidental ASD, physi-
lines recommended that patients with hemodynamically sig- cians should take into consideration the risk of RV failure as
nificant ASD undergo ASD closure to prevent these compli- well as how to control PH.
cations, regardless of symptom (1).
Many clinical studies have suggested that the clinical out- Case Report
come of patients who have pulmonary artery hypertension
(PAH) with associated ASD is also relatively good under A 40-year-old Korean man living in Japan visited the hos-
combination therapy of PAH-specific drug and ASD clo- pital with exertional dyspnea-based symptoms (WHO func-
sure (2, 3). However, the closure of small/coincidental ASDs tional class II). Based on a detailed clinical evaluation per-
in patients with PAH has been described as useless or even formed in his home country, the patient was diagnosed with
contraindicated in recent major guidelines for adult congeni- idiopathic pulmonary arterial hypertension (IPAH), along
tal heart disease (ACHD) (1, 4) and PH (5, 6). This is not with a small atrial septal defect (ASD); a genetic examina-
only because there is no evidence of any beneficial effects, tion of the mutations in genes such as bone morphogenetic
but also there is the potential risk of decompensated right protein receptor (BMPR) II and activin-like kinase (ALK)-1
ventricular (RV) failure due to the abolition of right-to-left was not performed. As generally recommended (1, 7, 8),
shunting, which acts as a pop-off valve unloading the RV. medical follow-up involving sildenafil was scheduled. In ad-
However, RV failure can progress when the left-to-right dition, the patient was advised to seek the medical opinion
shunt through the ASD is prominent, resulting in a degree of a Japanese hospital specializing in ACHD and PH, since

１
Department of Cardiovascular Medicine, The University of Tokyo Hospital, Japan and ２ Division for Health Service Promotion, The University
of Tokyo, Japan
Received: May 3, 2021; Accepted: July 5, 2021; Advance Publication by J-STAGE: August 31, 2021
Correspondence to Dr. Atsushi Yao, [email protected]

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Figure 1. Time course of medications and important parameters of hemodynamics and cardiac
magnetic resonance imaging. ASD: atrial septal defect, mPAP: mean pulmonary arterial pressure,
mPAWP: mean pulmonary arterial wedge pressure, mRAP: mean right atrial pressure, LVEF: left
ventricular ejection fraction, LVEDVI: left ventricular end-diastolic volume index, PVR: pulmonary
vascular resistance, Qp/Qs: pulmonary to systemic perfusion ratio, RVEDVI: right ventricular end-
diastolic volume index, RVEF: right ventricular ejection fraction, VO2: oxygen uptake

specialized hospitals in Japan have shown (9) or experi- observed was not due to ASD-based left-to-right shunt. The
enced (10) outstanding success in controlling IPAH. final diagnosis of PH was thus IPAH with a small ASD.
The first right heart catheterization (RHC) procedure re- We decided to evaluate the patient’s physiological and
vealed that a mean pulmonary arterial pressure (mPAP), pul- hemodynamic status using cardiac magnetic resonance imag-
monary vascular resistance (PVR), and pulmonary to sys- ing (cMRI) and RHC. The time course of medications and
temic perfusion ratio (Qp/Qs) of 55 mmHg, 5.5 wood units important parameters of cMRI and RHC are summarized in
(WU), and 1.6, respectively, which confirmed PH (Fig. 1). Fig. 1. cMRI and RHC in November 2014 showed an in-
Clinical evaluations conducted in other hospitals did not crease in the RV end-diastolic volume index (RVEDVI) with
yield any data indicative of a specific disease for PH Groups a reduced RV ejection fraction (RVEF), along with an im-
2 through 5; the PH exclusively belonged to Group 1 provement in mPAP (49 mmHg) and the PVR (5.1 WU)
(PAH). Although the Qp/Qs (=1.6) was relatively high, the with a prominent left-to-right shunt (Qp/Qs=1.4). The pa-
diameter of the ASD as measured by transesophageal echo- tient didn’t strictly take sildenafil, and fluid retention was
cardiography (TEE) was <20 mm, suggesting that the PAH suspected from the high mean pulmonary arterial wedge

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Figure 2. Changes in chest X-ray, electrocardiogram, and echocardiogram findings.

pressure (mPAWP) and mean right atrial pressure (mRAP). ments in cardiomegaly, inverted T waves, and RV enlarge-
The short-acting sildenafil was replaced with long-acting ment with compressed LV cavity (Fig. 2). The RHC showed
tadalafil, and two diuretics were administered. a further decrease in the mPAP (25 mmHg) without deterio-
In March 2015, there was a reduction in the mPAP with ration in the RV function. The patient’s peak VO2 in CPX
normalization of the mPAWP and mRAP, although the PVR testing at that time improved to 22.2 mL/kg/min (73% of
increased concomitantly with lower Qp/Qs. Ambrisentan the theoretical VO2 max).
was then added on to tadalafil. The patient’s peak oxygen One year after ASD closure, cMRI further showed that
uptake (peak VO2) in cardiopulmonary exercise (CPX) test- the RVEDVI was markedly reduced with no marked change
ing just after this was 16.5 mL/kg/min (58% of the theoreti- in the RVEF, implying that the RV had undergone reverse
cal VO2 max). In August 2016, the RVEDVI and Qp in- remodeling. However, three years after ASD closure, the pa-
creased with a reduction in the RVEF, while both the mPAP tient’s hemodynamic status worsened, supposedly due to his
and PVR improved further. The high Qp likely has a harm- poor adherence to the medical treatment. We noted a slight
ful effect on the RV function in addition to a successive increase in the mPAP (35 mmHg) and PVR (5.4 WU) on
downstream negative effect on the pulmonary arteries. As a RHC and an increased RVEDVI with a slightly reduced
result, the percutaneous closure of the ASD was therefore RVEF on cMRI. The patient’s peak VO2 in CPX testing de-
selected. creased to 15.6 mL/kg/min (57% of the theoretical VO2
With the informed consent of the patient, the ASD was max).
percutaneously closed. The TEE-based assessment yielded a We continued to educate the patient on medication adher-
secundum ASD of 10.4 mm×6.0 mm with good circumfer- ence to him, and he has since been additionally taking bera-
ential rims except for the aortic rim and superior rim (1.9 prost (360 μg). The RHC showed a decrease in mPAP (27
and 1.7 mm, respectively). The ASD size was considered mmHg) and PVR (4.2 WU). Four years after ASD closure,
too small to induce PAH from the left-to-right shunt, sug- the most recent cMRI scan showed an improvement in the
gesting again that IPAH was the main cause for his PAH. A RVEF (32%) and a decrease in the RVEDVI (100 mL/m2).
septal occluder (15-mm Figulla Flex II; Occlutech GmbH, Recently, his WHO functional class stabilized to I. He has
Jena, Germany) was chosen and placed. After confirming no particular complaints in his daily life.
that the closure of the ASD did not acutely influence the
hemodynamic status, the device was released for implanta- Discussion
tion. After the closure, we kept the Swan-Ganz catheter in-
serted until the next day and further observed that the mPAP Unrestricted ASD induces high Qp, leading to damage of
(32-36 mmHg) slightly increased in proportion to an in- the pulmonary endothelial cells and proliferation of vascular
crease in the mPAWP (18-20 mmHg) until the next day. smooth muscle cells, which finally results in PAH, or so-
On day 9 after repair, there was a slight reduction in Qp called shunt associated PAH (sPAH). The global guide-
to 6.4 L min-1, with slight decreases in the mPAP (30 lines (1, 4) have recommended patients with RV enlarge-
mmHg) and PVR (3.6 WU). The patient had stable vitals ment due to unrestricted ASD undergo ASD closure regard-
and was discharged on day 10 after repair. A follow-up ex- less of the symptoms in order to prevent further complica-
amination eight months later revealed apparent improve- tions, such as RV failure and sPAH. Recent reports on ASD-

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 Intern Med 61: 851-855, 2022 DOI: 10.2169/internalmedicine.7888-21

sPAH have demonstrated safe closure of unrestricted ASD

Conclusions
under controlled PAH using PAH-based therapeu-
tics (2, 11, 12). However, the closure of a small ASD in pa- The clinical decision to close a small or coincidental ASD
tients with IPAH has been described as unnecessary and in a patient with IPAH should not be based solely on exist-
even contraindicated as per major guidelines for PH (7, 8) ing guidelines but rather consider the benefit-risk ratio asso-
or ACHD (1). ciated with the specific case. Meticulous clinical monitoring,
The underlying reason for these guidelines is the lack of with attention to precise hemodynamic analyses using RHC
evidence concerning the beneficial effects of closing a small and cMRI, and prior experience in effective strategies for
ASD and its potential for inducing RV failure with the fur- controlling PAH are pertinent for making difficult clinical
ther collapse of the systemic circulation. However, there are decisions with regard to closure of a small ASD in a patient
chances of progression of RV failure when the left-to-right with IPAH.
shunt through the small ASD is prominent enough, espe-
cially under PH, to induce RV volume overload. Using The authors state that they have no Conflict of Interest (COI).
cMRI, we were able to clearly predict the timing of the RV
failure, which can occur due to volume overload through the
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14. Kjellstrom B, Sandqvist A, Hjalmarsson C, Nisell M, Nasman P,

Ivarsson B. Adherence to disease-specific drug treatment among The Internal Medicine is an Open Access journal distributed under the Creative
patients with pulmonary arterial hypertension or chronic throm- Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To
boembolic pulmonary hypertension. ERJ Open Res 6: 2020. view the details of this license, please visit (https://creativecommons.org/licenses/
by-nc-nd/4.0/).

Ⓒ 2022 The Japanese Society of Internal Medicine

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