A Digital Model to Explain the Necessity of Prostaglandin E1 After Balloon Atrial Septostomy in D-Transposition of the Great Arteries

Objective: Patients with D-transposition of the great arteries (TGA) often require prostaglandin E1 (PGE) even after balloon atrial septostomy (BAS). This study builds a computer simulation that analyzes whether or not elevated pulmonary vascular resistance (PVR) could explain the profound hypoxemia seen in some patients after PGE discontinuation. Methods: We developed a systems-based mathematical model of TGA incorporating systemic and pulmonary circulations, an atrial septal defect (ASD), and a patent ductus arteriosus (PDA), with bidirectional atrial mixing. The PGE-on pre-BAS state represented restrictive atrial communication, with systemic arterial saturation in the clinically expected 60–70% range. BAS was modeled by reducing ASD resistance and increasing the atrial mixing parameter; PGE withdrawal was modeled by increasing PDA resistance. A reproducible Monte Carlo cohort of 500 virtual patients was generated using independent probability distributions for heart rate, PVR, SVR, ASD resistance, PDA resistance, and atrial mixing. Prespecified sensitivity analyses varied ASD resistance reduction, PDA resistance, and pulmonary and systemic vascular responses to PGE withdrawal. Results: The PGE-on pre-BAS cohort had a median systemic arterial saturation of 64.7% (interquartile range, 59.1–68.8%), which increased to 74.7% (70.6–77.9%) after BAS. Following PGE withdrawal, saturation decreased to 70.9% (66.0–74.4%), while systemic flow increased from 1.83 to 2.04 L/min/m2 and systemic oxygen delivery increased from 271.4 to 283.9 mL O2/min/m2. For the response from PGE-on post-BAS to PGE-off post-BAS, each 1-WU·m2 increase in PVR was associated with a 0.56-percentage-point greater decrease in saturation, a 6.56% smaller increase in systemic flow, a 3.96% greater decrease in effective pulmonary flow, and a 7.87% smaller increase in oxygen delivery (all p < 0.01). Conclusions: In a model representing clinically restrictive pre-BAS atrial communication, PVR strongly modified the response to PGE withdrawal after BAS. Higher PVR was associated with larger decreases in saturation and effective pulmonary flow and smaller improvements in systemic flow and oxygen delivery. Saturation and oxygen delivery may move in opposite directions; therefore, assessment after PGE withdrawal should integrate systemic perfusion rather than rely on saturation alone. These findings are mechanistic and require external clinical validation.