Fetal Aortic Valvular Stenosis

• Compensatory Mechanisms: To maintain combined ventricular output (CVO), the right ventricle compensates by increasing its output. This leads to a greater proportion of inferior vena cava (IVC) blood being diverted into the right ventricle, and less flow through the foramen ovale into the left atrium. Consequently, the right ventricle contributes a larger percentage to CVO, while left ventricular output is reduced.

• The decrease 

• Ductus Arteriosus: The ductus arteriosus carries a greater blood flow than normal, as it becomes crucial in distributing blood to the descending aorta and ultimately, to the systemic circulation and placenta.

• Coronary Blood Flow: In severe cases, particularly with aortic atresia, coronary blood flow must be supplied by retrograde flow from the ductus arteriosus through the hypoplastic ascending aorta. This means that a portion of the coronary flow is provided in systole from the retrograde flow by the ductus. Impaired coronary blood flow and high end-diastolic pressure in the left ventricle can contribute to subendocardial ischemia and the development of endocardial fibroelastosis. This is further complicated by increased right atrial pressure, which may increase coronary sinus pressure (the drainage system of the coronary arteries). 

Progression to Hypoplastic Left Heart Syndrome (HLHS)

A significant concern with fetal aortic stenosis is its potential to progress to hypoplastic left heart syndrome (HLHS), a condition where the left ventricle and ascending aorta are poorly developed.

• Progressive Hypoplasia: Serial ultrasound studies in human fetuses have shown a relative decrease in left ventricular size with advancing gestation, suggesting that stenosis can worsen or that a moderately stenotic valve may not grow proportionally, becoming more obstructive.

• Predictive Factors: Factors strongly associated with progression to HLHS include:

  • Retrograde blood flow in the transverse aortic arch.

  • Left-to-right flow across the foramen ovale. Normally, flow is right-to-left.

  • Monophasic mitral valve inflow, suggesting abnormal diastolic filling of the left ventricle.

  • Moderate-to-severe left ventricular dysfunction.

  • Other markers may include significant duration of retrograde flow in the pulmonary veins (increased left atrial pressure), and increase RV systolic pressure by tricuspid regurgitant jet. Systemic arterial pressure in fetal lambs increases with gestational age, ranging from a mean of 25–30 mmHg at about 60 days' gestation (which is 0.4 gestation given a 150-day gestation period for lambs) to 55–60 mmHg closer to term. Left and right ventricular systolic pressures are similar to those in the ascending aorta and pulmonary trunk (reference: "Congenital Diseases of the Heart - 2009 - Abraham Rudolph"). As such, we can extrapolate that the RV systolic pressure mid-gestation to be around 30-40 mmHg in the human fetus. Increasing RV systolic pressure in the 60-70 at that gestational could be of concern. 

• Hydrops Fetalis: Severe aortic stenosis can lead to hydrops fetalis, which is generalized edema in the fetus, particularly if significant atrioventricular valve insufficiency develops, causing marked ventricular dilation. Hydrops indicates severe heart failure.

Fetal Diagnosis

Fetal echocardiography is the primary diagnostic tool.

• Early Detection: Advances in technology and diagnostic skills allow for earlier recognition of aortic valve obstruction.

• Echocardiographic Findings: Key clues include:

  • Thickened, immobile aortic valve.

  • Turbulent or decreased color Doppler flow across the aortic valve.

  • Dilated and dysfunctional left ventricle (LV).

  • Dilated left atrium (LA), potentially compressing the right atrium (RA) due to severe mitral regurgitation.

  • Endocardial fibroelastosis, appearing as bright hyperechogenic areas, especially in the LV apex and papillary muscles.

  • Evidence of restriction of the interatrial septum, such as left atrial dilation, bowing of the atrial septum from left to right, and altered pulmonary venous flow patterns (reduced forward flow in early diastole, increased retrograde flow during atrial systole).

• Limitations: Doppler-derived gradients across the aortic valve may not accurately represent stenosis severity due to associated LV dysfunction (and/or very limited flow through the valve, as well as presence of open ductus sending a right to left shunt to fill the aorta).

• Serial Monitoring: Sequential echocardiography is recommended to monitor for disease progression, as stenosis can increase in severity with advancing gestation.

Fetal Intervention

Fetal aortic valvuloplasty is a therapeutic procedure performed to relieve the obstruction in utero.

• Goal: The primary goal is to promote normal development of the left ventricle and increase the likelihood of achieving a biventricular circulation after birth, ideally preventing the progression to HLHS. This is still under investigation and the technique may be associated with complications for the fetus and the pregnant individual (rupture of membranes, bleed, infections, loss of the fetus, preterm labour, etc. This is true for any fetal procedure and should be done by expert centers). 

• Technique: The procedure involves a transabdominal and transuterine approach, where a needle is inserted into the fetal left ventricular apex, followed by the passage of a guidewire and balloon dilation catheter across the aortic valve. The balloon is then inflated to dilate the valve.

• Timing: Ideally, fetal aortic valvuloplasty should be performed under 30 weeks' gestational age. Early diagnosis is crucial, as earlier intervention is more likely to achieve optimal ventricular development.

• Outcomes and Considerations:

  • Success in relieving cardiac failure and increasing right ventricular size has been reported in cases of critical pulmonary stenosis.

  • Despite successful intervention, significant residual aortic valve obstruction and LV hypoplasia may still be present postnatally.

  • For hydropic fetuses, maternal digoxin administration may be attempted to relieve edema prior to valvuloplasty.

  • The criteria for selecting fetuses with aortic stenosis for intervention remain an area of ongoing study, as it is not fully understood what factors determine whether a fetus will progress to HLHS. Delaying intervention until advanced changes (e.g., markedly impaired LV function, considerable EFE) occur may limit the left ventricle's ability to provide adequate systemic blood flow after birth.

Associated Conditions

Fetal aortic stenosis can be associated with other left-sided stenotic lesions, including congenital mitral stenosis, bicuspid aortic valve, aortic arch hypoplasia, or coarctation of the aorta. The bicuspid aortic valve is the most common morphology and is often the substrate for congenital or acquired stenosis, frequently seen with coarctation of the aorta.

Fetal Echocardiography Example

View of the ductus arteriosus which is right to left but restrictive in pattern (turbulence) and high velocity. This is confirmed by the Doppler pattern. 

Peak systolic velocity is 20 mmHg. The pattern is non-pulsatile but rather restrictive with an almost saw-tooth appearance. The mean gradient is 7 mmHg and end-diastolic graident of 1.8 mmHg. A "restrictive pattern" of the ductus arteriosus (DA) refers to its abnormal narrowing or constriction, which impedes the normal blood flow and can lead to significant hemodynamic consequences. Systolodiastolic acceleration of flow through the ductus arteriosus with increased flow velocities in systole, early diastole, and late diastole.

2D and Colour mode. We can appreciate that there is septal and LV free wall hypertrophy. The LV is apex forming. The Mitral and Tricuspid valve are opening and closing. On the colour, we can appreciate the filling of the ventricular cavities. There is turbulence at the outflow portion of the left ventricle, due to the aortic valvular stenosis. 

M-Mode confirms the increased thickness at the septal level and LV posterior wall leve. 

Tricuspid insufficiency. Here the CW-Doppler provides an estimate of RV-RA gradient of 79 mmHg. The RA pressure in fetal life has a mean of around 3 mmHg. However, with the decreased right to left shunt at the atrial level (due to the increased LA pressure), the right atrial pressure is likely increased and neighbouring 4-5 mmHg. As such, the RV systolic pressure is estimated at 80 to 85 mmHg, which is elevated for a fetus at 25 to 35 weeks. 

Apical view with sweep. We can observe that there is atrio-ventricular concordance, and ventriculo-arterial concodance. The coronary sinus drains to the right atrium. The aortic valve is thick, with its leaflets not opening fully and with a narrowed LVOT. In the colour box, there is tricuspid insufficiency with the jet reaching the roof of the right atrium. There is acceleration at the aortic valve level.

Long axis view of the left ventricular outflow tract showcasing the thickened aortic valve leaflet, that are limited in their oepning. The annulus is well developped but the valve, which is bicuspid, is stenotic. The mitral valve is well developped. The LV seems "underfilled", although it is common in fetal life that the LV is less prominent than the RV which is the systemic ventricle and receives a significant preload from the IVC, SVC and ductus venosus (although part of which gets diverted to the LA by the FO). However, in the context of the aortic valve obstruction, one would have expected increased LV distension, which is not the case here, indicating that there is some decreased LV filling likely. 

Views outlining important sweeps. There is hypertrophy of the LV but the LV is apex forming. 

Short axis outlining the bicuspid aortic valve that is not fully opening during systole. 

Final Cardiac Evaluation:

• Congenital aortic valvar stenosis

• Congenital ascending aortic dilation

• Mild to moderate tricuspid regurgitation with a right ventricular to right atrial peak gradient of 78 mmHg.

• Moderate left ventricular hypertrophy.

• Bicuspid Aortic valve with thickened leaflets.

• Moderate aortic stenosis with a left ventricular to aortic peak gradient of 66 mmHg.

• Restrictive patent ductus arteriosus with right-to-left shunting.