Natural Antibodies and Left Ventricular Assist Device Complications

Abstract

Purpose Left ventricular assist devices (LVAD) are widely used as a bridge to heart transplantation or destination therapy for advanced heart failure. However, hemocompatibility-related complications such as pump thrombosis, stroke and bleeding remain frequent. We previously reported that LVAD implantation is followed by a sharp increase in serum levels of IgG natural antibodies (Nabs) recognizing oxidation-specific epitopes (OSE). 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 contribute to LVAD complications by modulating the coagulation cascade. Methods We studied a cohort of adult patients who received a continuous flow LVAD at Columbia University/NewYork Presbyterian Hospital. Nabs and anti-phospholipid antibodies (aPL) were measured in pre- and post-LVAD sera at 1, 6 and 12 months by assessing IgG reactivity to the OSE malondialdehyde (MDA) or β2-glycoprotein complexes by ELISA. In a subset of patients, Nabs were measured at day 1 to 7 post-implant. The effect of IgG Nabs on hemostasis was tested by rotational thromboelastometry (ROTEM) by adding IgG purified from pre- and post-LVAD serum to ABO blood type-matched donor blood. Wilcoxon's signed rank test for matched pairs or Mann-Whitney U test was used to compare measurements. Results Mean IgG Nabs levels were significantly increased in post-LVAD sera at 1 (7040±1680 ELISA units, p Conclusion Our studies revealed that serum IgG Nabs reactive to oxidized epitopes are elevated following LVAD implant. Appearance of Nabs was not accompanied by aPL increase. IgG Nabs prolonged the clotting time of donor whole blood, suggesting that Nabs modulate the coagulation pathway. These findings suggest that IgG Nabs may contribute to hemocompatibility-related complications in LVAD recipients.