Right ventricular dysfunction following surgical repair of tetralogy of Fallot: Molecular pathways and therapeutic prospects

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). Although surgical correction of TOF is possible, patients often face challenges related to right ventricle dysfunction (RVD) post-surgery, which can significantly impact their long-term survival. The causes of RVD in TOF patients are complex, involving both the unique structural characteristics of the TOF heart and damage resulting from surgical interventions. Residual anatomical issues following TOF repair are often unavoidable, placing the RV under stress and leading to the activation of multiple molecular pathways. This review comprehensively outlines the causes of RVD in patients after TOF surgery, particularly focusing the molecular pathways that contribute to RVD, including established signaling pathways as well as emerging pathways identified through transcriptomic analysis of RV myocardium in TOF patients. We also highlight the features of these molecular pathways concerning RVD, as well as the influence of gender disparities on these molecular pathways. By interpreting the causes and molecular mechanisms underlying RVD after TOF surgery, this review provides new insights for managing RVD in repaired TOF, potentially paving the way for targeted therapies aimed at improving long-term outcomes for those affected by RVD.