Hemodynamic consequences of a restrictive ductus arteriosus and foramen ovale in fetal transposition of the great arteries

1 Case

A 38 year old female was referred to the Fetal Heart Program for evaluation of suspected congenital heart disease at 22 weeks gestation and the diagnosis of D-transposition of the great arteries (D-TGA) was made. Further assessment revealed an unrestrictive foramen ovale (FO), with a hypermobile atrial septum primum, in which the atrial septum billowed back and forth between the left and right atrium (Fig. 1a). The ductus arteriosus (DA) was small (size of the branch pulmonary arteries) with bidirectional flow (Fig. 2a), suggesting a low pulmonary vascular resistance with concomitant increase in pulmonary blood flow. The middle cerebral artery (MCA) blood flow was normal with no evidence of increased diastolic flow (Fig. 3a). Follow-up study at 28 weeks gestation revealed similar findings. Fetal brain MRI, done as part of a research study, showed no structural or developmental abnormalities and was reported to be normal for gestational age.

At 32 weeks gestation, several important changes were noted. The hypermobile atrial septum was tethered superiorly and bowed leftward (Fig. 1b), and the right atrium and right ventricle were mildly dilated suggesting mild restriction at the FO. The DA was smaller than the branch pulmonary arteries and was tortuous, with restrictive flow that was mostly left to right through the cardiac cycle. In addition, color Doppler suggested multiple aorto-pulmonary collateral vessels in both lungs. Reversed flow within the left pulmonary artery was identified (Fig. 4) suggesting significant reversed flow in the distal left pulmonary artery likely from the aorto-pulmonary collateral vessels. MCA blood flow was again normal.

Fetal brain MRI was performed at 37 weeks gestation which revealed normal structure; however spectroscopy showed the presence of lactate. Fetal echocardiogram one week later revealed that the FO was closed, the left atrium and left ventricle were dilated (Fig. 1c), and there was decreased systolic and diastolic (monophasic mitral inflow) left ventricular function. The DA was tiny with continuous left to right flow (Fig. 2b). The branch pulmonary arteries also appeared dilated likely from a combination of the left to right ductal flow and the aorto-pulmonary collateral flow. MCA Doppler revealed significant diastolic flow suggesting cerebral vasodilation and “brain sparing” (Fig. 3b).

Given the fetal echocardiographic findings of a closed FO and decreased left ventricular function, the fetus was delivered at 38 weeks via Cesarean section in the Children’s National cardiac operating room with the cardiac catheterization team and cardiac intensivist present. An urgent balloon atrial septostomy was performed within 30 minutes of delivery. A prostaglandin infusion was initiated; however the DA remained tiny with minimal flow. Nitric oxide and 100% oxygen were started to treat presumed pulmonary hypertension. Despite a successful atrial septostomy, and initiation of prostaglandin and pulmonary vasodilators, the baby remained hypoxic (pre-balloon ABG with pH = 7.2 and pO₂= 20, post-balloon ABG with pH = 7.19 and pO₂= 19). The infant was transferred to the cardiac intensive care unit and inotropic support, with dopamine and epinephrine, were initiated to maintain blood pressure and adequate distal perfusion. Echocardiogram confirmed the diagnosis of D-TGA. The FO was wide open after intervention with all left to right flow, the DA remained tiny with left to right flow, and multiple aorto-pulmonary collaterals were visualized. Due to persistent hypoxia and hypotension despite maximum medical support, the baby was taken urgently to the operating room for surgical repair on day of life two. The postoperative course was uncomplicated and the baby was discharged at 15 days of life. Echocardiogram revealed no evidence for pulmonary hypertension and good biventricular function. Though asymptomatic, routine brain MRI prior to discharge revealed multiple tiny foci of white matter necrosis within the cerebral hemispheres and multiple focal thrombi within transverse sinuses.

2 Discussion

While surgical outcomes for the correction of D-TGA are excellent in the modern era, there continues to be significant morbidity and mortality in newborns with this disease which occurs primarily in the first minutes to hours of life due to persistent hypoxia and poor perfusion from closure of the FO. Improvements in fetal echocardiography have enabled the diagnosis of most congenital heart defects in-utero; however detection rates remain low for defects in which there are normal four chambers [1]. Once the diagnosis of congenital heart disease is made, strategies for stabilization of neonates in the delivery room may improve outcomes [2, 3]. Given the impact of prenatal diagnosis on postnatal outcomes in fetuses with D-TGA, it has been recommended that once the diagnosis has been made, the fetal echocardiogram should focus on the anatomy and flow at the FO and DA given that these structures may help to predict instability in the delivery room [3–6].

In normal fetal physiology, the inferior vena cava directs oxygenated blood flow from the placenta across the FO to enter the left side of the heart. In D-TGA, this oxygenated blood is directed to the pulmonary arteries instead of the aorta. It is believed that the high oxygen content in the pulmonary arteries is what leads to pulmonary dilation with increased blood flow into the branch pulmonary arteries and decreased or reversed flow across the DA. The resultant increased pulmonary venous return causes left atrial hypertension which may result in either decreased right to left FO flow or in some instances FO closure. In addition, increased pulmonary blood flow may result in proliferation of the smooth muscle within the pulmonary vascular bed increasing the pulmonary vascular resistance which may persist postnatally.

Up to 5% of patients with D-TGA have a severe and sometimes irreversible and fatal form of pulmonary vascular disease [7]. Theories regarding the cause of the abnormal pulmonary vasculature have been proposed but to our knowledge, observation of the ultrasound findings throughout mid and late gestation describing the progression of the abnormal fetal physiology have not been previously described. Recently, investigators using fetal MRI to assess blood flow in fetuses with D-TGA documented decreased FO flow and increased pulmonary artery and aorto-pulmonary collateral flow in a small number of fetuses studied late in gestation [8]. The authors propose that the increase in the amount of deoxygenated blood that perfuses the pulmonary arteries in-utero from FO restriction (decreased “red” blood in the left ventricle from less right to left FO flow) and left to right DA flow (increased “blue” blood in the pulmonary arteries from the aorta) may be the underlying etiology of aorto-pulmonary collateral formation due to the “relative hypoxia” in the fetal branch pulmonary arteries that occurs. In addition, they theorize that the increased pulmonary blood flow with more hypoxic blood is what likely contributes to the development of pulmonary vascular abnormalities that may occur before birth in these patients [8].

Postnatally, bronchial collaterals have been identified in babies with D-TGA; however most often they go undiagnosed preoperatively, likely due to minimal flow through the vessels due to vasoconstriction. Postoperatively after arterial switch operation, it has been reported that these vessels may cause an increased cardiac preload with left ventricular dilation and heart failure leading to difficulties weaning from mechanical ventilation [9].

Our case highlights the serial cardiovascular changes that may occur in mid-late gestation in fetuses with D-TGA, including severe ductus arteriosus constriction and aorto-pulmonary collateral formation, which we believe ultimately resulted in FO closure, left ventricular dysfunction, and postnatal pulmonary hypertension. The observations reported support the theory of aorto-pulmonary collateral formation in the setting of decreased right to left FO flow and left to right DA flow. Careful observation and interval in-utero follow-up of our patient gave us insight into the dynamic disease process and enabled us to direct specialized postnatal medical, interventional, and surgical team planning. In summary, in the setting of D-TGA with a restrictive or closed FO and a DA with bidirectional or left to right flow, there should be high suspicion for the development of aorto-pulmonary collateral formation and evolving pulmonary vascular abnormalities that may lead to instability post-delivery in both the pre- and postoperative periods despite successful balloon septostomy and specialized medical care.

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