Gastrointestinal bleeding and pro-angiogenic shift in the angiopoietin axis with continuous flow left ventricular assist device implantation

Background: Gastrointestinal bleeding (GIB) affects up to 40% of continuous-flow left ventricular assist device (CF-LVAD) recipients. A higher risk of GIB is seen in CF-LVAD recipients with lower device pulsatility without a known mechanism. One hypothesis is that the novel hemodynamics in CF-LVAD recipients affect angiogenesis signaling. We aimed to (1) measure serum levels of angiopoietin (Ang)-1, Ang-2, and VEGF-A in CF-LVAD recipients with and without GIB and in healthy controls and (2) evaluate correlations of those levels with hemodynamics. Methods: We recruited 12 patients with CF-LVADs (six who developed GIB after device implantation) along with 12 age-matched controls without heart failure or GIB and measured Ang-1, Ang-2, and VEGF-A levels in serum samples from each patient. Results: CF-LVAD recipients had significantly higher Ang-2 and lower Ang-1 levels compared to controls with no difference in VEGF-A levels. CF-LVAD recipients with GIB had lower Ang-1 levels than those without GIB. There were trends for pulse pressure to be positively correlated with Ang-1 levels and negatively correlated with Ang-2 levels in CF-LVAD recipients with no correlation observed in healthy controls. Conclusion: CF-LVAD recipients demonstrated a shift toward a pro-angiogenic phenotype in the angiopoietin axis that is significantly associated with GIB and may be linked to low pulse pressure.