Understanding the hemodynamic changes in fetuses with coarctation of the aorta using a lumped model of fetal circulation

Abstract

Coarctation of the aorta (CoA) is a common congenital heart defect characterized by aortic narrowing. Prenatally, it has mild hemodynamic effects as right ventricular disproportion and ductus arteriosus (DA) dilation occur as adaptive mechanisms, but their impact on CoA hemodynamics remains poorly understood. To investigate this, we built a closed 0D computational model of fetal circulation and simulated different CoA cardiovascular remodeling patterns, including aortic isthmus (AoI) narrowing, ventricular disproportion, and DA dilation. Our results showed mild AoI narrowing (80% of reference diameter) required up to 1.7 right/left ventricular end-diastolic volume ratio and 115% DA dilation to maintain physiological pressures, wall shear stresses, and organ perfusion. In contrast, severe narrowing (20% of reference AoI diameter) required up to 5 right/left ventricular end-diastolic volume ratio and 125% DA dilation, highlighting the necessity of co-occurrence of prenatal ventricular disproportion and DA dilation to compensate for AoI narrowing. These physiological regions were validated with ultrasonographic measurements from 7 controls and 9 CoA patients. We compared blood pressures, velocities, and volumetric flow rates across different fetoplacental anatomical sites. AoI velocity showed a delayed retrograde flow peak and increased antegrade diastolic velocity with greater AoI narrowing, which may aid in diagnosing CoA. Minimal differences were observed in other velocities and pressures. Volumetric flow rates across varying degrees of AoI narrowing decreased in the AoI and mitral and aortic valves, remained stable in the middle cerebral and umbilical arteries, and increased in the DA and tricuspid and pulmonary valves. Therefore, we corroborated that in fetal CoA a redistribution of blood flow occurs to ensure perfusion of the brain and placenta, without a significant alteration in fetal hemodynamics (blood pressure and velocities) except for increased diastolic velocities in the AoI.

Fig 1. Simplified anatomical configuration of the lumped computational model of fetoplacental circulation.

Fig 2. Comparison of the computational model’s healthy baseline simulated traces (black) with those obtained by ultrasound from control cases (grey), after manually tuning the model’s parameters to closely align with the confidence intervals (green).

Fig 3. Distribution of regions in which total blood flow, wall shear stress and pressures are below a 5% (dark green), 10% (medium green), and 15% (light green) change in the whole fetal body relative to the healthy values, or exceed that amount at any anatomical site (pink), for different combinations of aortic isthmus (AoI) narrowing, right-to-left ventricular end-diastolic volume (RV/LV EDV) ratio and ductus arteriosus (DA) dilation.

Real healthy and coarctation of the aorta (CoA) cases are marked with grey and white crosses, respectively. Points in which the percentage of change of the physiological region with respect to the healthy reference model is minimal are marked with grey, blue, purple, and red circles for 100%, 80%, 60%, and 40% of the reference aortic isthmus size, respectively.

Fig 4. Blood pressure, velocity, and volumetric flow rate (VFR) curves at left heart (LV: left ventricle, LA: left atrium, Av: aortic valve, Mv: mitral valve), right heart (RV: right ventricle, RA: right atrium, Pv: pulmonary valve, Tv: tricuspid valve), ductus arteriosus, aortic isthmus (AoI), middle cerebral artery, and umbilical artery obtained with the computational model at 100% (black), 80% (blue), 60% (purple) and 40% (red) of the reference aortic isthmus diameter size, for the combination of right-to-left ventricular end-diastolic volume ratio and ductus arteriosus dilation with minimum percentage of change compared to the healthy baseline.

Arrows in the aortic isthmus velocity indicate the onset of the reversed peak for the reference model and 40% of the reference aortic isthmus size.