Relationship of Vascular Endothelial Growth Factor C, a Lymphangiogenesis Modulator, With Edema Formation, Congestion and Outcomes in Acute Heart Failure

Background: Although vascular endothelial growth factor C (VEGF-C) is a known lymphangiogenesis modulator, its relationship with congestion formation and outcomes in acute heart failure (AHF) is unknown. Methods: Serum VEGF-C levels were measured in 237 patients hospitalized for AHF. The population was stratified by VEGF-C levels and linked with clinical signs of congestion and outcomes. Results: The study's population was divided in VEGF-C tertiles: low (median [Q25-Q75]: 33 [15-175]), medium (606 [468-741]) and high (1141 [968-1442] pg/mL). The group with low VEGF-C on admission presented with the highest prevalence of severe lower-extremity edema (low VEGF-C vs medium VEGF-C vs high VEGF-C): 30% vs 13% vs 20%; P = 0.02); the highest percentage of patients with ascites: 22% vs 9% vs 6%; P = 0.006; and the lowest proportion of patients with pulmonary congestion: 22% vs 30% vs 46%; P = 0.004. The 1-year mortality rate was the highest in the low VEGF-C tertile: 35% vs 28% vs 18%, respectively; P = 0.049. The same pattern was observed for the composite endpoint (death and AHF rehospitalization): 45% vs 43% vs 26%; P = 0.029. The risks of death at 1-year follow-up and composite endpoint were significantly lower in the high VEGF-C group. Conclusions: Low VEGF-C was associated with more severe signs of congestion (signs of fluid accumulation) and adverse clinical outcomes. (J Cardiac Fail 2023;29:1629-1638)