Case report
A female infant was born at 23 weeks and 1 day of gestation via vaginal delivery after preterm premature rupture of membranes. At 22 weeks and 0 days of gestation, a routine prenatal check-up revealed no abnormalities. However, at 22 weeks and 3 days of gestation, the mother noticed symptoms suggestive of membrane rupture. When she visited the referring hospital at 22 weeks and 5 days of gestation, the amniotic fluid was found to be almost completely depleted, indicating severe oligohydramnios. The birth weight was 494 g. After endotracheal intubation and surfactant administration, the neonate was admitted to the neonatal ICU.
Echocardiography by the neonatologist showed patent ductus arteriosus, patent foramen ovale, and no other obvious cardiac malformations, while left ventricular systolic function was good. Despite ventilatory support, oxygenation gradually deteriorated, with peripheral oxygen saturation decreasing to 86% under an inspired oxygen fraction of 0.35 on the first day of life. Inhaled nitric oxide therapy was initiated prior to cardiology consultation; however, the response was limited. Persistent cyanosis prompted consultation with a paediatric cardiologist on the 2nd day of life. The echocardiography revealed a significant narrowing of the right ventricular cavity, thickening of the right ventricular free wall measuring 3.8 mm, minimal antegrade pulmonary flow, trivial tricuspid regurgitation, and right-to-left atrial shunting. The ductus arteriosus showed continuous left-to-right shunt flow but was stenotic (Figure 1(a)–(g)). Based on these findings, the differential diagnoses included pulmonary atresia with intact ventricular septum, isolated right ventricular hypoplasia, and transient right ventricular hypertrophy. In any case, it was determined that maintaining pulmonary circulation required ductus arteriosus patency, and prostaglandin E1 (standard alprostadil formulation, 167 ng/mL) was initiated at an extremely low dose of 1.1 ng/kg/min. After the initiation of prostaglandin E1, oxygenation improved rapidly, with peripheral oxygen saturation increasing to 99% under room air. Inhaled nitric oxide therapy was subsequently tapered and discontinued. Systemic blood pressure remained stable, and fluid management was carefully performed using a central venous catheter during the early postnatal course, without the need for vasopressors or systemic steroids. On the 3rd day of life, although pulmonary circulation was maintained, increased ductal flow raised concerns about the development of symptomatic ductus arteriosus. Prostaglandin E1 was gradually tapered and discontinued due to widening of the pulse pressure and a reduction in diastolic flow in the superior mesenteric artery on Doppler echocardiography. The ductus arteriosus had sufficiently dilated, and pulmonary circulation was maintained. On the 4th day of life, the foramen ovale showed left-to-right shunting, and antegrade flow from the right ventricle was confirmed (Figure 2(a)–(b)). Widened pulse pressure and decreased urine output suggested symptomatic patent ductus arteriosus. It was judged that pulmonary circulation could be maintained by antegrade pulmonary flow, and indomethacin treatment was initiated. On the 6th day of life, intestinal perforation occurred, requiring emergency laparotomy and colostomy creation. Since no significant ischaemic changes were observed, the perforation was not caused by ischaemia from symptomatic patent ductus arteriosus but by tissue immaturity associated with prematurity. Further indomethacin was contraindicated. Ductus arteriosus ligation was performed on the 19th day of life. The postoperative haemodynamics stabilised, and organ perfusion improved. Subsequently, chylothorax developed, which resolved spontaneously with conservative management. On the 118th day of life, which was the expected delivery date, echocardiography showed the adequate expansion of the right ventricular cavity, and no findings were suggestive of myocardial hypertrophy or pulmonary hypertension, leading to a diagnosis of transient right ventricular hypertrophy (Figure 2(c)–(f)). The colostomy closure surgery was performed on the 172nd day of life, and the patient was discharged on the 250th day of life with a body weight of 3330 g.
(a–g) Echocardiographic findings on the 2nd day of life. (a, b) The four-chamber and short-axis views showing a significantly small right ventricular cavity. (c) Colour Doppler image from the right ventricular outflow tract to the pulmonary artery, where antegrade flow was unclear. (d) Colour Doppler image at the atrial level demonstrating a right-to-left shunt through the foramen ovale. (e) Pulsed Doppler image at the foramen ovale. (f) Ductal flow. (g) The continuous-wave Doppler image of the ductus arteriosus demonstrating a continuous left-to-right flow pattern.
(a–c) The echocardiographic findings 2 days after initiation of PGE1 therapy. (a) The colour Doppler image of the right ventricle to the pulmonary artery demonstrating antegrade flow. (b) The colour Doppler image at the atrial level demonstrating a left-to-right shunt through the foramen ovale. (c) Pulsed Doppler image at the foramen ovale. (d– g) The echocardiographic findings on the 118th day of life (term-equivalent age). (a) The four-chamber view showing a well-expanded right ventricular cavity. (b) The colour Doppler image at the atrial level showing a left-to-right shunt through the foramen ovale. (c ) Long-axis view. (d) Short-axis view.
Discussion
In the present case, transient right ventricular myocardial hypertrophy was observed in the neonatal period, accompanied by a significant narrowing of the right ventricular cavity. However, the right ventricular cavity eventually expanded, and the myocardial hypertrophy was resolved. The right ventricular morphology at birth and uncertain antegrade pulmonary flow made differentiation from isolated right ventricular hypoplasia or pulmonary atresia with intact ventricular septum. Due to the presence of a right-to-left atrial shunt and uncertain antegrade pulmonary flow, ductus-dependent pulmonary circulation could not be ruled out, requiring the early administration of prostaglandin E1.
Pulmonary hypertension was considered an important differential diagnosis during the acute phase; however, several findings argued against it as the primary cause of right ventricular wall thickening. Oxygenation improved dramatically after prostaglandin E1 initiation, allowing discontinuation of inhaled nitric oxide, while systemic blood pressure remained stable without vasopressors or steroids. On echocardiography, tricuspid regurgitation was trivial, preventing estimation of right ventricular pressure, and the ductus arteriosus consistently demonstrated continuous left-to-right shunting, which is atypical for significant pulmonary hypertension. These findings make secondary right ventricular hypertrophy due to pulmonary hypertension unlikely in the present case. Hypovolemia was also considered in the differential diagnosis; however, it was considered unlikely, as systemic blood pressure remained stable under carefully controlled fluid management, and echocardiography did not demonstrate findings suggestive of significant intravascular volume depletion.
Transient right ventricular hypertrophy in neonates is rare. Fetal stress, maternal diabetes, and steroid administration have been reported as potential contributing factors. The prognosis is generally favourable, as the hypertrophy tends to resolve spontaneously. Reference Tomar, Radhakrishnan and Shrivastava1–Reference Mirand-Mallea, Perez-Verdu and Gasco-Lacalle3 This case has shown that in transient right ventricular hypertrophy, where it is difficult to differentiate from CHDs such as isolated right ventricular hypoplasia Reference Hirono, Origasa and Tsuboi4 or pulmonary atresia with intact ventricular septum, assessing the presence of ductus-dependent circulation can be extremely challenging.
Giordano et al. proposed an echocardiographic scoring system to predict ductus-dependent circulation, incorporating parameters like tricuspid valve diameter, right ventricular cavity area, and interatrial communication in cases of pulmonary atresia with intact ventricular septum and critical pulmonary stenosis. Reference Giordano, Santoro and Gaio5 Since the minimum birth weight in that study was 1.7 kg, the scoring system could not be applied to the present case. Ultimately, due to the narrowed right ventricular cavity, unclear antegrade pulmonary flow, and a right-to-left atrial shunt, the possibility of ductus-dependent pulmonary circulation could not be excluded, and the administration of prostaglandin E1 was decided.
On the 4th day of life, antegrade pulmonary flow was confirmed, which ruled out pulmonary atresia. Differentiation between transient right ventricular hypertrophy and isolated right ventricular hypoplasia relies on serial echocardiography to assess progressive right ventricular dilation and haemodynamic improvement. In the present case, the right ventricular cavity had sufficient enlargement and improved function on the 118th day of life, leading to the diagnosis of transient right ventricular hypertrophy.
Moreover, most reports on transient right ventricular hypertrophy involve term infants, and studies in extremely low birth weight infants have not been established. The present case provides valuable findings suggesting the occurrence of transient right ventricular hypertrophy in this population. While maternal diabetes or antenatal steroid exposure was absent, oligohydramnios due to the preterm premature rupture of membranes might have contributed to intermittent fetal hypoxia, which could lead to transient pressure overload of the right ventricle. In the present case, preterm premature rupture of membranes occurred around 22 weeks of gestation and was followed by several days of severe oligohydramnios. Although definitive evidence of pulmonary hypoplasia or placental pathology suggestive of chronic abruption–oligohydramnios sequence was unavailable, prolonged oligohydramnios during a critical period of fetal development may have contributed to intermittent fetal hypoxia and increased right ventricular load, potentially leading to transient myocardial remodelling.
Management of ductus arteriosus in preterm infants is challenging. While ductus arteriosus is essential for maintaining pulmonary circulation, it also frequently contributes to complications such as pulmonary congestion and impaired organ perfusion. Pharmacologic closure with indomethacin was attempted but discontinued after intestinal perforation. Ultimately, the surgical ligation stabilised haemodynamics. Postoperative chylothorax, likely related to surgical intervention and immature lymphatics, resolved spontaneously.
Even with potential ductus-dependent pulmonary circulation, prostaglandin E1 was administered at an extremely low dose of 1.1 ng/kg/min due to concerns that excessive ductal dilation might result in symptomatic patent ductus arteriosus. Despite the low dose, the patient eventually developed symptomatic patent ductus arteriosus, highlighting the delicate balance required in extremely low birth weight infants. Serial echocardiography allowed careful titration of therapy and monitoring of right ventricular function.
In retrospect, the timing of prostaglandin E1 tapering and discontinuation was guided by haemodynamic and echocardiographic markers suggestive of emerging systemic steal. Widening of the pulse pressure and a reduction in diastolic flow in the superior mesenteric artery on Doppler echocardiography raised concern for the development of symptomatic patent ductus arteriosus, prompting discontinuation of prostaglandin E1. These findings underscore the importance of careful Doppler assessment of systemic organ perfusion when balancing ductal-dependent pulmonary circulation against the risk of symptomatic patent ductus arteriosus in premature infants.
As demonstrated in this case, even when right ventricular hypoplasia is suspected after birth, serial echocardiographic evaluation is crucial to distinguish true hypoplasia from transient hypertrophy. Although the myocardial hypertrophy was transient and fully resolved, an underlying genetic cardiomyopathy cannot be entirely excluded, and genetic testing may be considered if abnormal myocardial remodelling or dysfunction emerges during long-term follow-up. To facilitate the assessment of ductus-dependent circulation and the appropriate use of prostaglandin E1 in such situations, the development of diagnostic criteria tailored specifically for very low birth weight infants is needed.
Financial support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
The authors declare no conflict of interest.
