Sustained Elevation of Vascular Endothelial Growth Factor Levels Following Transcatheter Aortic Valve Replacement

Background: Alterations in the levels VEGF were described after various transcatheter vascular interventions. We evaluated serum vascular endothelial growth factor (VEGF) levels and its correlation to cardiac function following transcatheter aortic valve replacement (TAVR).

Methods: From an initial cohort of 70 consecutive TAVR patients, we excluded patients with conditions known to affect VEGF levels (i.e. comorbidities, TAVR complications), and serum VEGF, including standardization to platelets count, was assessed by ELISA. We then assessed the angiogenic propensity of serum collected from post-TAVR patients in vitro, using endothelial adhesion, cord-like structure formation, and survival assays. VEGF levels’ correlation to cardiac function was evaluated by echocardiography.

Results: Analysis was performed on 46 patients (81±6y, F=19). Serum VEGF was significantly elevated 2 and 30 days after TAVR (5.4 and 4 fold of baseline levels, respectively, p<0.005). VEGF rise did not correlate with neither C-reactive protein (CRP) nor creatine phosphokinase (CPK), implying for a substantial angiogenic shift, rather than transient reaction to tissue injury. Subsequently, post-TAVR serum markedly stimulated endothelial cells’ expression of VEGF-receptor 2 (VEGFR2) and adhesion molecules. Adhesion, cord-like formation capacity, and survival during apoptotic stimuli of endothelial cells treated with post-TAVR serum were significantly improved, compared to treatment with pre-TAVR serum. VEGFR2 inhibition by SU5416 markedly abolished these effects. The magnitude of serum VEGF rise was associated with a decrease in estimated pulmonary systolic arterial pressure (EPASP) and an increase in the fractional area change of the right ventricle by (r=0.54, p p<0.03, respectively). Among patients with elevated baseline EPASP, VEGF rise was significantly higher, compared to normal baseline EPASP (p<0.05).

Conclusions: A substantial, long lasting, elevation in serum VEGF occurs after TAVR, reflecting a systemic angiogenic shift. VEGF might serve as a potential marker of improvement in pulmonary hypertension in TAVR patients.