VEGFA and heart failure: Edema was seen in 4.8% of patients on a pioglitazone monotherapy vs. 1.2% on placebo.[3] Vascular endothelial growth factor (VEGF) also has been implicated as a causal factor in thiazolidinedione-induced edema.[4] The increase in plasma volume related to thiazolidinediones may result from a reduction in renal excretion of sodium and an increase in sodium and free water retention and this fluid retention in turn can aggravate cardiac failure.