Left-Ventricular Assist Device Is Associated with Elevated Serum Levels of Natural IgG Reactive to Apoptotic Cells and Oxidized Epitopes

Abstracts S91 in an increase in score of each domain of QOL: physical =  0.50; psychological =  0.49; social =  0.20; and environmental =  0.34. Conclusion: We report the first data of the significant relationships among self-efficacy, adherence, and QOL in patients with LVADs. The findings also inferred that higher levels of patient’s self-efficacy and adherence to LVAD treatment regimen results in greater improvement in QOL. Thus, self-efficacy and adherence should be accounted in future QOL studies for patients with long-term LVADs. 2( 25) A Multicenter Quality of Life (QoL) Survey Regarding LVAD Drivelines: A Look Beyond the Medical Aspects L.J. Bogar ,1 S. Phillips,2 F.D. Pagani,3 N.A. Haglund,4 J.A. Cowger,5 S. Maltais,6 A. Ravichandran,7 J.M. Stulak,6 M. Binetti,8 M. Lefebvre,9 S.E. Womak,4 P. Shah.2  1Cardiac Surgery, Inova Fairfax Heart and Vascular Institute, Falls Church, VA; 2Heart Failure and Transplantation, Inova Fairfax Heart and Vascular Institute, Falls Church, VA; 3Cardiac Surgery, University of Michigan Hospital, Ann Arbor, MI; 4Cardiolgy, Vanderbilt, Nashville, TN; 5Cardiology, St. Vincent Heart Center of Indiana, Indianapolis, IN; 6Cardiac Surgery, Mayo Clinic, Rochester, MN; 7Cardiac Surgery, St. Vincent Heart Center of Indiana, Indianapolis, IN; 8Advanced Heart Failure and Transplant, Inova Fairfax Heart and Vascular Institute, Falls Church, VA; 9Cardiolgy, University of Michigan Hospital, Ann Arbor, MI. Purpose: LVAD drivelines are often the cause of QoL dissatisfaction for patients. We sought to define the most common concerns regarding drivelines and QoL issues both initially and over time. We also hypothesized that patients’ dominant handedness compared to the side of driveline exit may impact satisfaction and incidence of infection. Methods: Anonymous paper surveys were completed by LVAD patients while in the office [n= 113; 71 Heartmate II (HM2), 35 HeartWare (HW) and 7 unspecified]. The survey was conducted by the Mechanical Circulatory Support Research Network (MCSRN) institutions. Patient self-reported health indicators, QoL and demographics were explored. Results: Overall driveline satisfaction mean was 7.7 (on a scale of 1-10 with 10 being most satisfied). Only 5 (4%) of all patients wished to change the side of their driveline exit. Mean satisfaction was similar for patients with opposite side exit (7.43) versus same side exit (7.85); p= .316. Satisfaction for HM2 (7.9) and HW (7.4) patients was also comparable; p= .223. Patients were provided a list of QoL improvements related to their drivelines. The top two QoL improvements requested are: ability to submerge in water and unrestricted showering (Figure 1). First year patients were more impacted by ‘weight of external components’ and ‘sleep comfort’ (p =  0.037 and 0.056, respectively). Patients >  1 year were more impacted by concern for driveline tugs (p =  0.049). Patients with drivelines on the same side as their dominant hand had selfreport of infection comparable to patients with opposite side drivelines (19% vs 25%); p= 0.46. Conclusion: Overall, patient satisfaction with their LVAD drivelines was good. Satisfaction between HM2 and HW was comparable. Handedness in relation to driveline exit side seemed to play no role on satisfaction or selfreported incidence of driveline infection. Totally implantable LVADs of the future will hopefully alleviate some of the patients’ top QoL concerns.

2( 26) Left-Ventricular Assist Device Is Associated with Elevated Serum Levels of Natural IgG Reactive to Apoptotic Cells and Oxidized Epitopes S.B. See ,1 P.J. Kennel,2 M. Weber,2 K. Rogers,1 D. Chatterjee,1 Y. Gu,1 G. Vlad,3 K.J. Clerkin,2 V.K. Topkara,2 P.C. Colombo,2 D.M. Mancini,2 Y. Naka,4 M.A. Farr,2 E.R. Vasilescu,3 S.W. Restaino,2 P.C. Schulze,2 E. Zorn.1  1Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY; 2Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY; 3Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY; 4Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Medical Center, New York, NY. Purpose: Left-ventricular assist device (LVAD) implants are widely used as a bridge to heart transplantation. While LVAD implantation has been associated with increased production of HLA-reactive antibodies, little is known about the effect on non-HLA antibodies. We hypothesized that natural antibodies (Nab) reactive to apoptotic cells and oxidized epitopes are also enhanced after LVAD support. We sought to determine their presence and assess their impact on post-transplant complications. Methods: We studied 214 pediatric and adult patients who received a heart transplant at Columbia University/New York Presbyterian Hospital between 2011 and 2014. Nab were detected in pre-transplant serum samples by assessing the IgG reactivity to apoptotic Jurkat cells by flow cytometry and to the oxidation-specific epitope malondialdehyde (MDA) by ELISA. IgG Nab levels were compared between patients who had received LVAD (N= 105) and those who did not (N= 109). Correlation between Nab measurements and post-transplant complications including primary graft failure (PGF), infection, antibody-mediated rejection, cellular rejection and cardiac allograft vasculopathy (CAV) was evaluated using Mann-Whitney U test. Results: IgG Nab levels were significantly elevated in LVAD patients compared to non-LVAD patients when tested by reactivity to apoptotic cells (flow cytometry; 451 ± 28.66 vs 216.6 ± 15.43 MFI, p< 0.001) and MDA (1.56 ± 0.06 vs 0.50 ± 0.06 ELISA units, p< 0.001). In the LVAD group, increased levels of IgG Nab reactive to MDA were significantly associated with CAV diagnosed by angiography at any time during follow-up (p< 0.05). Elevated pre-transplant IgG Nab levels were also associated with PGF (p< 0.05) but not serious infection or rejection at 1 year. Conclusion: Our studies suggest that LVAD support increases serum levels of IgG Nab reactive to apoptotic cells and oxidized epitopes in a manner comparable to the increase observed for anti-HLA antibodies. Taken together, these findings support the idea of an overall non-specific B cell activation following LVAD implantation, resulting in sensitization. Moreover, their association with the development of CAV and PGF suggests that IgG Nab could have predictive significance for both complications. 2( 27) T-Cell Dependence of Antibody Response to Blood Group A-Antigen I. Adam ,1 B. Motyka,2 K. Tao,2 J. Pearcey,2 L. West.3  1Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada; 2Pediatrics, University of Alberta, Edmonton, AB, Canada; 3Depts. of Pediatrics, Surgery, and Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada. Purpose: ABO-incompatible heart transplantation (ABOi HTx) is safe during infancy and allows increased access to donors. B-cell tolerance develops to donor A/B antigen(s) (Ag) following ABOi HTx, but mechanisms of tolerance are not well-defined. Using recently developed A-transgenic (A-Tg) mice (B6 background) expressing human A-Ag on vascular endothelium and erythrocytes (RBC), we investigated the role of CD4+ T-cells in anti-A antibody (Ab) production. Methods: Wild-type C57BL/6 mice (WT) were injected i.p. x3, 1 week apart with human blood group A RBC (hu-A) with (n= 3) and without (n= 6) CD4-depleting mAb (GK1.5), or A-Tg RBC (n= 12) and adjuvant. Anti-A Ab in serum was measured by hemagglutination and ELISA (both IgG and IgM). Four weeks later, A-Tg RBC-injected mice were injected i.p. with hu-A-RBC; anti-A was measured again. To study the effect of human