Animal Models of Repaired Tetralogy of Fallot: Current Applications and Future Perspectives

Tetralogy of Fallot is the most common cyanotic congenital heart disease. Despite ongoing improvements in the initial surgical repair, there are lingering concerns regarding the long-term outcomes that may be complicated by right ventricular dysfunction, right ventricular dyssynchrony, and sudden cardiac death. The mechanisms leading to these late complications remain incompletely understood. Experimental animal models have been developed as preclinical steps to gain better insight into the pathophysiology of diseases and to develop new therapeutic strategies. This article summarizes the various types of experimental animal models of repaired tetralogy of Fallot published to date in the literature, with the aim of achieving a greater understanding of the deleterious mechanisms that may lead to these known late and sometimes lethal complications. In addition to analysing the type of animals that can be used according to a given study's objectives, needs, and constraints, the present review also evaluates the type of dysfunction that can be reproduced in our model according to the research objectives, as well as the different types of studies in which these models can be used. In view of all that, we propose a decision algorithm to create an animal model of repaired tetralogy of Fallot. This synthesis should furthermore help in the development of future studies and in the design of new experimental models, thus allowing greater insight into this disease, while not forgetting the ultimate goal of broadening future therapeutic measures to reduce the morbidity and mortality of this prevalent congenital heart disease.