Mitral regurgitation and pulmonary hypertension accompanied by
premature restriction of the foramen ovale are associated with the
ductus arteriosus
Naoki Ohashi1), Hidenori Yamamoto1),
Hajime Sakurai2), Kazuki
Matsumoto3), Kentaro Suzuki3), Ishin
Syu3), Jun Sato3), Kimihiro
Yoshii3), Shuichiro Yoshida3),
Hiroshi Nishikawa3)
Department of Pediatrics, Children’s Heart Center, Nagoya University
Hospital1)
Department of Cardiosurgery, Children’s Heart Center, Nagoya University
Hospital2)
Department of Pediatric Cardiology, Chukyo Children Heart Center, Japan
Community Healthcare Organization Chukyo Hospital, Nagoya,
Japan3)
Correspondence to: N. Ohashi, MD,PhD
Department of Pediatrics, Children’s Heart Center, Nagoya University
Hospital
65 Tsurumai-cho, Showa-Ku, Nagoya 466-8560, Japan.
Tel: +81-52-744-2294
Fax: +81-52-744-2974
E-mail: ohashi-n@med.nagoya-u.ac.jp
Abstract
Two cases of severe mitral regurgitation and pulmonary hypertension
immediately after birth are presented. Initial echocardiographic
findings showed a thick atrial septum rather than a normal flap septum.
The patients were tentatively diagnosed with premature restriction of
the foramen ovale and congenital mitral regurgitation. Subsequently, the
mitral regurgitation resolved over time with improvement of pulmonary
hypertension. The postnatal ductus arteriosus closure process was
considered to be the cause of the mitral regurgitation and pulmonary
hypertension.
Introduction
It has been noted that some neonates with premature restriction of the
foramen ovale (PRFO) have severe pulmonary hypertension (PH)(1), and PRFO may be associated with hypoplastic left
heart syndrome (2). On the other hand, the role of the
ductus arteriosus (DA) in the fetal and postnatal circulations with PRFO
patients is unknown. PRFO with normal heart structure can lead to right
ventricular volume loading, severe tricuspid regurgitation, and PH,
which may result in congestive heart failure, hydrops, or even fetal
death (3). In the present cases, hemodynamic changes
in mitral regurgitation (MR) and PH during the clinical course of the
postnatal period were associated with hemodynamic changes in the DA.
Case report
Case1
This male patient was born of a normal vaginal delivery at a gestational
age of 40 weeks 4 days at another hospital, and his birth weight was
3708g with Apgar scores of 9 at one minute and 10 at five minutes.
A cardiac murmur was noted 1 day after birth, and a patent DA was
diagnosed. The patient was discharged from the hospital 4 days after
birth. At the outpatient clinic, the echocardiogram showed severe MR,
severe tricuspid regurgitation (TR), and severe PH (Figure 1), and the
patient was transferred to our hospital 8 days after birth. The atrial
septum was very thick, and interatrial communication was very narrow
with bidirectional shunt (Figure 2). There was a very small patent DA,
and bidirectional shunt was confirmed (Figure 3). A tentative diagnosis
of PRFO was made based on the findings. Oxygen inhalation, continuous
intravenous administration of milrinone (0.5 µg/kg/min), and a diuretic
venous infusion were started and reductions to mild TR, and moderate MR,
along with improvement of PH, were observed as acute effects 9 days
after birth. However, MR and PH worsened again 10 days after birth, and
diuretic doses were increased. MR and PH improved gradually, DA closure
was confirmed 13 days after birth, and the patient was discharged 23
days after birth.
Case2
This male patient was born in a suction delivery at a gestational age of
38 weeks 1 day at another hospital. His birth weight was 2678g, and the
Apgar scores were 8 in one minute and 9 at five minutes. Respiratory
distress developed gradually, and oxygen inhalation was started.
Respiratory distress developed, and the patient was transferred to
another hospital 2 days after birth. The echocardiogram findings showed
severe MR and severe PH. Furthermore, mechanical ventilation was
initiated for progressive respiratory distress. The patient was then
transferred to our hospital for treatment. The echocardiogram showed
that the degree of MR shifted from mild to severe according to the
degree of PH, which changed from mild to severe (Figure 4). The atrial
septum was thick, and interatrial communication was through a very tiny
left-to-right shunt (Figure 5). On the other hand, the right-to-left
shunt due to DA increased with exacerbation of PH (Figure 6). Continuous
intravenous injection of milrinone (0.5 µg/kg/min) and an intravenous
diuretic were started. Decrease of MR to a mild level, improved PH, and
DA closure were confirmed as acute effect 4 days after birth. However, a
PH crisis due to infection occurred 7 days after birth. Eight days after
birth, recanalization of the DA and severe deterioration of MR were
confirmed, and a DA ligation procedure was performed. Subsequently,
surgery was performed for gastric perforation, which had occurred as a
complication. Although long time was needed for the MR and PH to
improve, the patient was discharged 83days after birth.
Discussion
Premature closure or restriction of the foramen ovale is a rare but
known entity. Foramen ovale diameter <2 mm, Doppler velocity
>120 cm/s, diameter <3 mm with a Doppler velocity
measured gradient >5 mmHg have all been used by various
authors to describe this entity (4). PRFO could result
in pathological conditions associated with right heart volume overload
or left heart volume underload, including right ventricular failure,
fetal hydrops, supraventricular tachycardia, and left heart obstructive
defects. On the other hand, PRFO can also result from increased left
atrial pressure due to cardiac disease with left ventricular inflow
obstruction, as with aortic stenosis, mitral stenosis, or ventricular
diastolic dysfunction. PRFO in hearts with normal structure can lead to
right ventricular volume loading, severe tricuspid regurgitation, and
PH, which may result in congestive heart failure, hydrops or even fetal
death. It has been reported that whether and when fetal death occurs is
influenced by the timing of PRFO. However, it is unclear when PRFO
develops into hydrops or even fetal death, and other factors may be
involved.
The present patients were born at full term without hydrops. The
echocardiogram findings immediately after birth showed a very thick
atrial septum and very small interatrial shunt and unmeasurable foramen
ovale diameter. The reason for no hydrops may be the presence of a very
small foramen ovale, which provided decompression in the fetal period.
Initially, interatrial communication was a bidirectional shunt in case 1
and a left-to-right shunt in case 2. On the other hand, left ventricular
function was poor in both cases, probably because of decreased coronary
perfusion due to low cardiac output associated with left heart volume
underload caused by PRFO and MR due to mitral valve deformity subsequent
to left ventricular compression as a result of right ventricular
dilation caused by PRFO. Interatrial communication disappeared with
improvement of PH and cardiac function.
Regarding the DA, which plays an important role in the fetal
circulation, in the initial period after birth, there was a small DA
with a bidirectional shunt in case 1, and the right-to-left shunt of the
DA increased with exacerbation of PH in case 2. PRFO inevitably causes
an increase in pulmonary blood flow due to additional blood flow from
the placenta that should enter the left ventricle through the foramen
ovale if the foramen ovale is patent. Furthermore, oxygen content in the
pulmonary artery due to more oxygenated blood from the placenta may
synergistically contribute to an increase in pulmonary flow by lowering
pulmonary artery resistance (5). Therefore, we
consider that prenatal blood flow through the DA may be increased, so
that the postnatal closing process of the DA may have more impact on the
clinical course of PRFO. In case 1, the small DA with a bidirectional
shunt closed with improvements of MR, PH, and left heart function. In
case 2, the small DA had dilated when the DA provided decompression as a
right-to-left shunt compared to the left-to-right shunt of the DA.
Although the DA closed temporarily due to improvement of PH,
recanalization of the DA occurred with exacerbation of PH.
Hemodynamic changes in MR and PH may be related to hemodynamic changes
in the DA (Figure 7). The closing process of the DA increases preload of
blood flow to the left ventricle and results in volume overload of the
left ventricle, subsequently inducing MR. Furthermore, mitral valve
deformity caused by right ventricular dilation with PRFO adds to
enhancement of MR. As a result, a vicious cycle in which MR exacerbates
PH occurs.
In the present cases, acute effect was observed after initial medical
treatment, however, but it took some time for MR and PH to improve. The
mechanism is thought to involve insufficient left ventricular training
in reducing left ventricular preload by PRFO, PH with increasing of
pulmonary blood flow due to PRFO, and MR caused by mitral valve
deformity due to right ventricular dilation with PRFO. Mild improvement
of left ventricular function was observed as the acute effect, but it
appeared to take some time for left ventricular function to adapt.
In the hemodynamics of PRFO, the mechanism of MR/PH is thought to
involve the process of DA closure, which is necessary for postnatal
decompression of PH. In the present cases, the very narrow interatrial
communication of the PRFO and the large DA provided decompression of the
right ventricular volume loading and PH in fetal period, and the
postnatal process of DA closure may have been associated with MR and PH
pathology.
Conclusion
MR and PH accompanied by PRFO appear to be associated with the DA.
Declaration of interest
The authors declare that they have no known competing financial
interests or personal relationships that could have influenced, or
appear to influence, the work reported in this paper.
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