Fontan Circulation and lipidomics

Fontan circulation is associated with impaired cardiac output, reduced exercise capacity, and systemic metabolic stress. However, the underlying lipidomic alterations remain poorly defined. Using untargeted mass spectrometry, we analyzed 291 lipids in fasting plasma from 20 Fontan patients and 20 matched controls. Forty-eight lipids differed significantly (p < 0.05), with reductions in LPC and LPC(O), and increases in PS and ceramides. Key species such as LPC(O-22:1), LPC(O-20:0), and PS 40:5 showed strong correlations with stroke index, cardiac index, and VO₂max (|r| > 0.5, p < 0.001) and discriminated Fontan patients from controls (AUC > 0.78). Network and pathway analyses implicated mitochondrial–peroxisomal dysfunction and inflammatory remodelling, highlighting lipid alterations linked to reduced cardiovascular reserve in Fontan physiology.