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

LAY SUMMARY: Acute heart failure (AHF) is a state accompanied by lymphatic system dysregulation. Current knowledge of lymphatic system involvement in the episode of AHF is limited. The lymphatic system is known to be highly responsible for edema formation. In our work, we focused on the analysis of the Vascular Endothelial Growth Factor C (VEGF-C), a known factor responsible for lymphatic system development with AHF symptoms and survival. Our studies presented that low VEGF-C serum levels on admission are associated with more severe signs of accompanying AHF fluid accumulation (defined as ascites and lower extremities edema) and higher mortality rates when compared to medium and high VEGF-C serum levels on admission. Our conclusion is that VEGF-C may be used as a parameter that reflects lymphatic system function in AHF.

BACKGROUND: Although VEGF-C is a known lymphangiogenesis modulator, its relationship with congestion formation and outcomes in AHF is unknown.

METHODS: Serum VEGF-C level was 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 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). Low VEGF-C group on admission presented 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 one-year mortality was the highest in 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 one-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.