Leveraging Preclinical Modeling for Clinical Advancements in Single Ventricle Physiology: Spotlight on the Fontan Circulation

Preclinical modeling of human circulation has been instrumental in advancing cardiovascular medicine. Alongside clinical research, the armamentarium of computational (e.g., lumped parameter or computational fluid dynamics) and experimental (e.g., benchtop or animal) models have substantially enhanced our understanding of risk factors and root causes for circulatory diseases. Recent innovations are further disrupting the boundaries of these preclinical models toward patient-specific simulations, surgical planning, and postoperative outcome prediction. This fast-paced progress empowers preclinical modeling to increasingly delve into the intricacies of single ventricle physiology, a rare and heterogeneous congenital heart disease that remains inadequately understood. Here, we review the current landscape of preclinical modeling (computational and experimental) proposed to advance clinical management of a prominent yet complex subset of single ventricle physiology: patients who have undergone Fontan-type surgical corrections. Further, we explore recent innovations and emerging technologies that are poised to bridge the gap between preclinical Fontan modeling and clinical implementation.