Association of Angiopoetin-2 and TNF-α With Bleeding During Left Ventricular Assist Device Support: Analysis From the PREVENT Biorepository

Abstract

The purpose of this study was to describe the changes in plasma levels of angiogenic and inflammatory biomarkers, specifically Ang-2 and TNF-α, in patients receiving HeartMate II (HMII) left ventricular assist device (LVAD) and correlate them with nonsurgical bleeding. It has been shown that angiopoietin-2 (Ang-2) and tissue necrosis factor-α (TNF-α) may be linked to bleeding in LVAD patients. This study utilized biobanked samples prospectively collected from the PREVENT study, a prospective, multicenter, single-arm, nonrandomized study of patients implanted with HMII. Paired serum samples were obtained in 140 patients before implantation and at 90 days postimplantation. Baseline demographics were as follows: age 57 ± 13 years, 41% had ischemic etiology, 82% male, and 75% destination therapy indication. In the 17 patients with baseline elevation of both TNF-α and Ang-2, 10 (60%) experienced a significant bleeding event within 180 days postimplant compared with 37 of 98 (38%) patients with Ang-2 and TNF-α below the mean (p = 0.02). The hazard ratio for a bleeding event was 2.3 (95% CI: 1.2–4.6) in patients with elevated levels of both TNF-α and Ang-2. In the PREVENT multicenter study, patients with elevations in serum Angiopoietin-2 and TNF-α at baseline before LVAD implantation demonstrated increased bleeding events after LVAD implantation.