1
S100 The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014 Purpose: With improved device technology and longer waiting times for transplant, pts spend more time supported with left ventricular assist devices (LVADs). We sought to determine the rates of allosensitization with LVADs and its effect on the post-transplant outcomes. Methods: We retrospectively reviewed all bridge-to-transplant (BTT) pts implanted with the Heartmate II from 2004-2012. Allosensitization was assessed both by the complement-dependent cytotoxicity (CDC) and single bead Luminex assays. Pts were sensitized if the total B cell reactivity was above 10% by CDC and any HLA positivity by Luminex. Results: 105 BTT pts were transplanted with a mean age of 53.3±1.3 and 81.9% were males. During LVAD support, 61 (58%) were sensitized based on CDC, and 47 (77%) were newly sensitized during LVAD therapy. 55 pts had Luminex data, 27 pts (55%) were sensitized and 24/27 (89%) newly sensitized. Sensitized pts were younger 51.4±1.7 vs 56.1±1.8 (p=0.03) and more predominantly female, 22% vs 11% (p=0.2). All other demographics were similar. Sensitization based on either assay was associated with a sig- nificantly higher rate of AMR, 19.7 vs 4.6% in CDC (p=0.04) and 22% vs 0% in Luminex group, (p=0.01) (figure). These differences remained when we compared newly sensitized pts to non-sensitized with 20.0 vs 4.5% in CDC (p=0.05) and 37.5 vs 6.8% in Luminex group (p=0.04). No difference in CMR and CAV were observed. Conclusion: Allosensitization during CF-LVAD approaches 60%, with a majority of pts newly sensitized. These pts demonstrated a five-fold increase in risk of developing AMR following heart transplant. Larger cohorts and longer follow-up are required to determine the effect on graft function and survival. ( 259) Increasing Use of Mechanical Circulatory Support as a Bridge to Cardiac Retransplantation K.J. Clerkin , 1 S.S. Thomas, 1 J. Haythe, 1 P.C. Schulze, 1 M. Farr, 1 H. Takayama, 2 U.P. Jorde, 1 N. Uriel, 1 S.W. Restaino, 1 Y. Naka, 2 D.M. Mancini. 1 1 Cardiology, Columbia University Medical Center, New York, NY; 2 Cardiac Surgery, Columbia University Medical Center, New York, NY. Purpose: Cardiac retransplantation (ReTx) rates have gradually risen from 1.9% in 2000 to 2.6% in 2006 to 3.0% in 2012. As the donor shortage con- tinues and wait-list times lengthen, mechanical circulatory support (MCS) is increasingly used as a bridge to transplant and ReTx (8.3% of ReTx patients nationwide from 1988-2009). In July 2006, changes to the heart allocation algorithm were made to increase organ sharing. We sought to determine the impact of this policy change on MCS use in ReTx candidates. Methods: From 2000-2012 978 adult patients underwent orthotropic heart transplantation at Columbia University Medical Center (CUMC). A retro- spective review showed 80 patients were listed for ReTx, 47 patients (4.8%) underwent ReTx, and 15 bridged with MCS. Results: In Era 1 (2000-June 2006), 37 patients were listed for ReTx and 43 patients were listed in Era 2 (July 2006-2012). There was a trend towards greater MCS use following the policy change (Era 1, 10.8% vs. Era 2, 25.6%, p=0.09), and acute rejection became a more common indica- tion (Table, p<0.005). Between eras there was no significant difference in wait-list survival among ReTx candidates (Era 1, 84.6% vs. Era 2, 72.6%, p=0.64). Further, the wait-list time to ReTx for the MCS group in Era 2 was significantly shorter than for those without MCS support (130±94 days vs. 565±427, p=0.04), but this did not translate to a difference in wait-list survival. Conclusion: This study demonstrates that in the current era at CUMC, MCS use is used to support over a quarter of the patients awaiting ReTx following the heart allocation change. This trend in increasing use is likely to continue as the effectiveness of MCS in this scenario has been demonstrated, national wait-list times continue to increase, and donor hearts remain scarce. 47±56%. The mean time on support was 589±479 days for the sensitized patient as compared to 280±246 days for the entire BTT cohort. 4 patients had LVAD-related infections (3 had driveline infection and 1 had bacterial endocarditis). Post HT, mean follow-up time was 1030±788 days. 3/14 patients died 9, 428 and 476 days post-HT from hyper-acute rejection, severe graft failure, and sepsis, respectively. 5/14 patients developed Antibody-Mediated Rejection (AMR grade 1-i) based on the biopsy results at a mean of 169±339 days post-HT, although 4 developed early AMR within a mean time of 17±8 days post-HT. Only 1 patient was hemodynamically unstable. 3 patients had high-grade cellular rejection with a mean time of 384±385 days post-HT, and 1/3 had concomitant AMR. Graft dysfunction was diagnosed by echocardiogram in 5 patients in a mean time of 280 ±359 days post-HT. No patients developed transplant vasculopathy during the follow-up period. Conclusion: Desensitization therapy during LVAD support in BTT patients carries a risk of infection and patients remain at high risk of AMR and increased risk for early graft failure. ( 257) Do Continuous Flow Left Ventricular Assist Devices Really Cause Allosensitization? C.A. Willis , 1 J. Stehlik, 1 D. Eckels, 2 O. Wever Pinzon, 2 A. Kfoury, 2 S.G. Drakos, 2 R. Alharethi, 2 J. Nativi Nicolau, 2 D. Budge, 3 J.C. Fang, 2 E.M. GIlbert, 2 C.H. Selzman, 2 J. Stehlik. 2 1 Cardiology, University of Utah, Salt Lake City, UT; 2 Cardiology, U.T.A.H. Cardiac Transplant Program, Salt Lake City, UT; 3 Cardiology, U., Salt Lake City, UT. Purpose: The use of left ventricular assist devices (LVAD’s) as bridge to trans- plantation (BTT) has become routine, with 40% of all adult transplants now occurring in patients with an assist device. It has been suggested that, compared to pulsatile LVADs, sensitization in patients with newer continuous flow (CF) LVAD’s is less likely. This finding has not been consistent among studies, however. Methods: A retrospective review of all U.T.A.H. patients who received BTTCF- LVAD since 2006 was performed. Serum alloantibodies were identified with single-antigen beads using a Luminex platform. Sensitization was defined as a calculated panel reactive antibody (cPRA)>10%. Wilcoxon rank sum, and Chi- square tests were used as appropriate. Results: During the study period, 92 patients received CF-LVAD implant for BTT, including 78 Heart Mate II, 11 Jarvik 2000 and 12HeartWare LVAD’s. Before LVAD implant, 14.1% of patients met the sensitization criterion and this number increased to 30.4% after LVAD implant (p=0.02). The mean cPRA value in sensitized patients also increased, from 25.1% to 49.7%, p<0.001.In transplant candidates without LVAD(N=195), the sensitization indices at the time of their listing were similar to those seen in LVAD patients at the time of LVAD implant. Somewhat unexpectedly, by the time of transplant, the percentage of sensitized patients and the mean cPRA also increased in this group of transplant candidates who did not receive LVAD (Table 1). Conclusion: This study suggests that sensitization in transplant candidates with newer generation CF-LVADs is frequent. However, we also found that a significant proportion of transplant candidates who do not receive an LVAD become sensi- tized while awaiting transplantation. We conclude that sensitizing events in trans- plant candidates unrelated to mechanical assist are more frequent than previously thought and may have been incorrectly attributed to the effect of LVAD therapy. ( 258) Five -Fold Increase in Antibody-Mediated Rejection (AMR) Post- Heart Transplant in Patients Developing Allosensitization During Left Ventricular Assist Device Support (LVAD) K.P. Mody , 1 J. Duong, 1 M. Dionizovik-Dimanovski, 1 A.P. Levin, 1 A.R. Garan, 1 J. Fried, 1 H. Takayama, 2 M. Yuzefpolskaya, 1 P.C. Colombo, 1 S.W. Restaino, 1 Y. Naka, 2 D.M. Mancini, 1 U.P. Jorde, 1 N. Uriel. 1 1 Medicine, Columbia University, New York, NY; 2 Surgery, Columbia University, New York, NY.

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Page 1: Do Continuous Flow Left Ventricular Assist Devices Really Cause Allosensitization?

S100 The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014

Purpose: With improved device technology and longer waiting times for transplant, pts spend more time supported with left ventricular assist devices (LVADs). We sought to determine the rates of allosensitization with LVADs and its effect on the post-transplant outcomes.Methods: We retrospectively reviewed all bridge-to-transplant (BTT) pts implanted with the Heartmate II from 2004-2012. Allosensitization was assessed both by the complement-dependent cytotoxicity (CDC) and single bead Luminex assays. Pts were sensitized if the total B cell reactivity was above 10% by CDC and any HLA positivity by Luminex.Results: 105 BTT pts were transplanted with a mean age of 53.3±1.3 and 81.9% were males. During LVAD support, 61 (58%) were sensitized based on CDC, and 47 (77%) were newly sensitized during LVAD therapy. 55 pts had Luminex data, 27 pts (55%) were sensitized and 24/27 (89%) newly sensitized. Sensitized pts were younger 51.4±1.7 vs 56.1±1.8 (p= 0.03) and more predominantly female, 22% vs 11% (p= 0.2). All other demographics were similar. Sensitization based on either assay was associated with a sig-nificantly higher rate of AMR, 19.7 vs 4.6% in CDC (p= 0.04) and 22% vs 0% in Luminex group, (p= 0.01) (figure). These differences remained when we compared newly sensitized pts to non-sensitized with 20.0 vs 4.5% in CDC (p= 0.05) and 37.5 vs 6.8% in Luminex group (p= 0.04). No difference in CMR and CAV were observed.Conclusion: Allosensitization during CF-LVAD approaches 60%, with a majority of pts newly sensitized. These pts demonstrated a five-fold increase in risk of developing AMR following heart transplant. Larger cohorts and longer follow-up are required to determine the effect on graft function and survival.

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Increasing Use of Mechanical Circulatory Support as a Bridge to Cardiac RetransplantationK.J. Clerkin ,1 S.S. Thomas,1 J. Haythe,1 P.C. Schulze,1 M. Farr,1 H. Takayama,2 U.P. Jorde,1 N. Uriel,1 S.W. Restaino,1 Y. Naka,2 D.M. Mancini.1 1Cardiology, Columbia University Medical Center, New York, NY; 2Cardiac Surgery, Columbia University Medical Center, New York, NY.

Purpose: Cardiac retransplantation (ReTx) rates have gradually risen from 1.9% in 2000 to 2.6% in 2006 to 3.0% in 2012. As the donor shortage con-tinues and wait-list times lengthen, mechanical circulatory support (MCS) is increasingly used as a bridge to transplant and ReTx (8.3% of ReTx patients nationwide from 1988-2009). In July 2006, changes to the heart allocation algorithm were made to increase organ sharing. We sought to determine the impact of this policy change on MCS use in ReTx candidates.Methods: From 2000-2012 978 adult patients underwent orthotropic heart transplantation at Columbia University Medical Center (CUMC). A retro-spective review showed 80 patients were listed for ReTx, 47 patients (4.8%) underwent ReTx, and 15 bridged with MCS.Results: In Era 1 (2000-June 2006), 37 patients were listed for ReTx and 43 patients were listed in Era 2 (July 2006-2012). There was a trend towards greater MCS use following the policy change (Era 1, 10.8% vs. Era 2, 25.6%, p= 0.09), and acute rejection became a more common indica-tion (Table, p< 0.005). Between eras there was no significant difference in wait-list survival among ReTx candidates (Era 1, 84.6% vs. Era 2, 72.6%, p= 0.64). Further, the wait-list time to ReTx for the MCS group in Era 2 was significantly shorter than for those without MCS support (130±94 days vs. 565±427, p= 0.04), but this did not translate to a difference in wait-list survival.Conclusion: This study demonstrates that in the current era at CUMC, MCS use is used to support over a quarter of the patients awaiting ReTx following the heart allocation change. This trend in increasing use is likely to continue as the effectiveness of MCS in this scenario has been demonstrated, national wait-list times continue to increase, and donor hearts remain scarce.

47±56%. The mean time on support was 589±479 days for the sensitized patient as compared to 280±246 days for the entire BTT cohort. 4 patients had LVAD-related infections (3 had driveline infection and 1 had bacterial endocarditis). Post HT, mean follow-up time was 1030±788 days. 3/14 patients died 9, 428 and 476 days post-HT from hyper-acute rejection, severe graft failure, and sepsis, respectively. 5/14 patients developed Antibody-Mediated Rejection (AMR grade 1-i) based on the biopsy results at a mean of 169±339 days post-HT, although 4 developed early AMR within a mean time of 17±8 days post-HT. Only 1 patient was hemodynamically unstable. 3 patients had high-grade cellular rejection with a mean time of 384±385 days post-HT, and 1/3 had concomitant AMR. Graft dysfunction was diagnosed by echocardiogram in 5 patients in a mean time of 280 ±359 days post-HT. No patients developed transplant vasculopathy during the follow-up period.Conclusion: Desensitization therapy during LVAD support in BTT patients carries a risk of infection and patients remain at high risk of AMR and increased risk for early graft failure.

(257)

Do Continuous Flow Left Ventricular Assist Devices Really Cause Allosensitization?C.A. Willis ,1 J. Stehlik,1 D. Eckels,2 O. Wever Pinzon,2 A. Kfoury,2 S.G. Drakos,2 R. Alharethi,2 J. Nativi Nicolau,2 D. Budge,3 J.C. Fang,2 E.M. GIlbert,2 C.H. Selzman,2 J. Stehlik.2 1Cardiology, University of Utah, Salt Lake City, UT; 2Cardiology, U.T.A.H. Cardiac Transplant Program, Salt Lake City, UT; 3Cardiology, U., Salt Lake City, UT.

Purpose: The use of left ventricular assist devices (LVAD’s) as bridge to trans-plantation (BTT) has become routine, with 40% of all adult transplants now occurring in patients with an assist device. It has been suggested that, compared to pulsatile LVADs, sensitization in patients with newer continuous flow (CF) LVAD’s is less likely. This finding has not been consistent among studies, however.Methods: A retrospective review of all U.T.A.H. patients who received BTTCF-LVAD since 2006 was performed. Serum alloantibodies were identified with single-antigen beads using a Luminex platform. Sensitization was defined as a calculated panel reactive antibody (cPRA)> 10%. Wilcoxon rank sum, and Chi-square tests were used as appropriate.Results: During the study period, 92 patients received CF-LVAD implant for BTT, including 78 Heart Mate II, 11 Jarvik 2000 and 12HeartWare LVAD’s. Before LVAD implant, 14.1% of patients met the sensitization criterion and this number increased to 30.4% after LVAD implant (p= 0.02). The mean cPRA value in sensitized patients also increased, from 25.1% to 49.7%, p< 0.001.In transplant candidates without LVAD(N= 195), the sensitization indices at the time of their listing were similar to those seen in LVAD patients at the time of LVAD implant. Somewhat unexpectedly, by the time of transplant, the percentage of sensitized patients and the mean cPRA also increased in this group of transplant candidates who did not receive LVAD (Table 1).Conclusion: This study suggests that sensitization in transplant candidates with newer generation CF-LVADs is frequent. However, we also found that a significant proportion of transplant candidates who do not receive an LVAD become sensi-tized while awaiting transplantation. We conclude that sensitizing events in trans-plant candidates unrelated to mechanical assist are more frequent than previously thought and may have been incorrectly attributed to the effect of LVAD therapy.

(258)

Five -Fold Increase in Antibody-Mediated Rejection (AMR) Post-Heart Transplant in Patients Developing Allosensitization During Left Ventricular Assist Device Support (LVAD)K.P. Mody ,1 J. Duong,1 M. Dionizovik-Dimanovski,1 A.P. Levin,1 A.R. Garan,1 J. Fried,1 H. Takayama,2 M. Yuzefpolskaya,1 P.C. Colombo,1 S.W. Restaino,1 Y. Naka,2 D.M. Mancini,1 U.P. Jorde,1 N. Uriel.1 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY.