Natural Antibodies and Left Ventricular Assist Device Complications

Abstract

Left ventricular assist devices (LVAD) are widely used as a support strategy for advanced heart failure. Complications such as thrombosis and bleeding have been linked to LVAD. We observed that LVAD implantation was followed by a sharp increase in serum levels of IgG natural antibodies (Nabs) recognizing oxidation-specific epitopes (OSE) and apoptotic cells. Nabs have been implicated in inflammatory reactions related to atherosclerosis, ischemic stroke and primary graft dysfunction following heart transplantation. However, the consequence of IgG Nabs production following LVAD is not known. We hypothesized that Nabs generated following implant may be associated with LVAD complications, promoting thrombosis, stroke or bleeding. We studied a multicenter cohort (n=71) of adult patients who received a continuous flow LVAD at Columbia University Irving Medical Center (CUIMC), Virginia Commonwealth University (VCU) and Baylor University Medical Center (BUMC). Nabs were measured in pre- and longitudinal post-LVAD sera by assessing IgG reactivity to the OSE malondialdehyde (MDA) by ELISA and to apoptotic Jurkat cells by flow cytometry. Wilcoxon's signed rank test for matched pairs was used to compare measurements. Mean IgG Nabs levels were significantly increased in post-LVAD sera at 1 (0.41±0.05 Nabs units, p<0.0001), 6 (0.63±0.074, p<0.0001) and 12 months (0.49±0.69, p=0.0004) compared to pre-LVAD (0.19±0.021). Kinetics of Nabs development was found to differ between centers with 90.9% of CUIMC patients developing elevated Nabs at 6 months post-implantation compared to 30% and 29.7% for BUMC and VCU, respectively. Preliminary analysis revealed elevated Nabs in 2/3 VCU patients with pump thrombosis and 1/2 with stroke within the first year post-LVAD. Our studies revealed that serum IgG Nabs reactive to oxidized epitopes and apoptotic cells are elevated following LVAD implant. The appearance of Nabs differed between the centers. and we are investigating the possible contribution of differing perioperative procedures on Nabs development. Preliminary findings suggest that IgG Nabs may be associated with thromboembolism. Analysis of Nabs and adverse events in the other centers are forthcoming.