Rosaria Barracano, Gabriele De Palma, Claudia Montanaro, Vito Casale, Nunzia Borrelli, Antonella Bruna Cutrì, Micol Rebonato, Ippolita Altobelli, Gianfranco Butera, Giancarlo Scognamiglio, Berardo Sarubbi
The Fontan procedure has rewritten the natural history of many children with congenital heart disease and univentricular physiology. However, long-term survival is limited by the development of haemodynamic and multisystem failure, leading to high morbidity and mortality. Absence of a subpulmonary ventricular pump, chronically elevated central venous pressure, and reduced cardiac output, along with lymphatic dysfunction and progressive multiorgan involvement, define the clinical course of many patients with the Fontan procedure, resulting in the heterogeneous clinical entity of Fontan failure. This review provides a comprehensive overview of the pathophysiological mechanisms underlying Fontan failure and a critical analysis of the currently available advanced therapeutic options. Particular attention is paid to the current frontiers of mechanical circulatory support. Although the presence of a total cavopulmonary connection may represent an anatomical limitation, ventricular assist devices have gained attention both as a bridge to transplantation and, in selected cases, as a long-term strategy. Nonetheless, despite the high surgical complexity, heart transplantation currently represents the only definitive option for this patient population. Optimizing clinical outcomes in Fontan failure represents one of the most challenging frontiers in congenital heart disease. Achieving significant advances will require accurate risk stratification, timely transition to advanced therapies, and coordinated multidisciplinary collaboration.