Gamma-glutamyl transferase as a mediator in the association between ventricular dysfunction and systolic function

Introduction and objectives Heart failure involves multiorgan dysfunction; the heart–liver axis underlies the concept of the cardiohepatic syndrome. This study evaluated gamma-glutamyl transferase (GGT) as a mediator between left ventricular dysfunction and systolic function. Methods A cross-sectional analysis was performed using secondary data from 567 patients hospitalized for heart failure. The relationships between left ventricular end-diastolic diameter (LVEDD), GGT, and left ventricular ejection fraction (LVEF) were assessed using Hayes’ PROCESS mediation model 4. Multiple linear regressions were adjusted for comorbidities and clinical variables. The indirect effect was estimated through bootstrap resampling with 5000 iterations. A directed acyclic graph was used to represent the causal hypothesis. Results A significant association was observed between LVEDD and GGT (B = 5.13; P =.044), suggesting a direct link between cardiac impairment and increased hepatic marker levels. GGT was inversely associated with LVEF (B = −0.021; P =.009), and LVEDD also showed a negative association with LVEF (B = −2.40; P <.001). Mediation analysis revealed a significant indirect effect of LVEDD on LVEF through GGT (−0.11; 95%CI: −0.23 to −0.005), supporting the mediating role of this enzyme in the cardiohepatic axis. Conclusions GGT may act as a mediator between ventricular dysfunction and reduced LVEF in patients hospitalized with heart failure, reflecting a clinically relevant cardiohepatic interaction.