Getting personal: understanding how genetic variation affects clinical outcomes in patients with tetralogy of Fallot.

The work by Jeewa et al. is an important step toward “personalizing” or individualizing our approach to care of patients with tetralogy of Fallot. Although future studies will need to confirm the potential role of HIF1A-mediated signaling in right ventricular remodeling, it raises the possibility that modulation of the HIF1A signaling pathway or its downstream effectors such as TGF-β may allow better preservation of ventricular function in patients with TOF. Furthermore, directed genotyping for HIF1A and other genetic variants may help identify patients at risk for adverse outcomes. This study demonstrates the potential for genetics-of- outcomes studies to evaluate novel therapeutic targets and to identify at-risk populations that may require specific therapeutic considerations.