Experimental Venous Congestion Causes Peripheral Release of Angiopoietin-2 and Tissue Necrosis Factor-α - A New Insight into the Pathophysiology of Gastrointestinal Bleeding in CF-LVAD Patients

Purpose Gastrointestinal bleeding (GIB) from angiodysplasia is the most frequent cause of readmission in LVAD patients. Angiogenesis, inflammation and coagulopathy as well as venous congestion (VC) are hypothesized to contribute to GIB pathophysiology. We used an established experimental model of peripheral VC to investigate whether increased venous pressure alters plasma levels of angiopoietin-2 (Ang-2) tumor necrosis factor-α (TNF-α) and vonWillebrand factor (vWF). Methods 42 ambulatory patients with NYHA functional class II or III, LVEF Results Patients were 54±12 years, 32% female, with mean LVEF=22±8% and 32% had an ischemic etiology. Pretest, baseline plasma levels of Ang-2, TNF-α and vWF were 6.73±0.70 ng/ml, 1.90±0.10 pg/ml, and 1.52±0.14 U/ml, respectively. Plasma Ang-2 and TNF-α increased in the congested (vs control arm) after 90 minutes of VC: 7.01±0.71 vs 6.69±0.67 ng/ml, p Conclusion We provide the first evidence that experimental peripheral VC is sufficient to increase circulating angiogenic and inflammatory biomarkers in HF patients. Future studies are warranted to investigate whether aggressive control of peripheral VC may prevent development and/or progression of angiodysplasia and thereby reduce the risk of GIB in CF-LVAD patients.