Institutional report - Assisted circulation sensitisation and post-transplant course after the implantation of ventricular assist device
Vilnius University, Vilnius, Lithuania.Interactive Cardiovascular and Thoracic Surgery (Impact Factor: 1.16). 03/2009; 8(3):339-42; discussion 342-3. DOI: 10.1510/icvts.2008.192567
The purpose of this study was to evaluate sensitisation, occurring because of bridging with VAD, and development of rejection episodes after transplantation in selected groups of patients using triple drug immunosuppression, without induction or desensitisation therapy. Sensitisation using standard complement dependent cytotoxicity was tested in 16 patients awaiting cardiac transplantation before VAD placement, one month post-implantation and on a six-monthly basis later on. Long-term (955+/-998 days) post-transplant course of six transplanted post-VAD patients was compared with 19 non-bridged recipients (follow-up time 1425+/-1273 days) of the same age. One-third of VAD recipients had developed anti-HLA antibodies one month post-implantation; 4/16 patients were sensitised six months after implantation. No de novo sensitisation development was revealed in VAD group post-transplantation. All sensitised patients independent of VAD placement underwent graft rejection episodes. Only 1 of 6 VAD recipient was treated because of grade 2R rejection, compared to 6/19 in the non-bridged group, P=0.63. None of the patients had failed because of early graft rejection. In conclusion, VAD devices used in our centre cause low level risk for anti-HLA antibodies development. There were no differences in survival due to immunologic reasons between VAD bridged and non-bridged patients.
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ABSTRACT: Background: Left ventricular assist devices (LVAD) as a bridge (BTT) to heart transplantation (HTX) may be limited by the formation of anti-human leukocyte antigen antibodies. Whether sensitization occurs with continuous axial flow LVAD implant as assessed by single antigen bead (SAB) assay is unknown. Methods: Cytotoxic panel-reactive antibody (PRA) and SAB assays were analyzed in HTX recipients undergoing LVAD implant as a BTT. Sensitization was defined as peak anti-human leukocyte antigen antibody values of more than 2000 mean fluorescence intensity because these values have been found to correlate with flow cytometric crossmatch results. Results: LVADs were implanted as BTT in 30 patients. There were 7% (2 of 30) of patients before LVAD implant and no patients after LVAD implant with PRA more than 10%. However, 20% (6 of 30) of patients before LVAD and 53% (16 of 30) after LVAD were sensitized as measured by SAB (P=0.024). At HTX, 47% (14 of 30) of patients remained sensitized. A positive virtual crossmatch was observed in 28% (4 of 14) of the sensitized patients at HTX. There was no difference between the sensitized and nonsensitized groups (P>0.4 for all) in usage of blood products (6411 vs. 6339 units) and time to HTX (28,663 vs. 25,748 days), and 1 year after HTX, there were no differences in rejection (total rejection score 0.30 vs. 0.37) and survival (93% vs. 88%). Conclusion: Allosensitization after LVAD is common despite cytotoxic PRA being negative. One year after HTX, this sensitization does not translate into increased acute cellular or antibody-mediated rejection or reduced survival.
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ABSTRACT: Recent data suggest that Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device improves waiting list survival for pediatric heart transplant candidates. Little is known about their post-transplant outcomes. The aim of this analysis was to determine whether there was a difference in early survival for children bridged to transplant with EXCOR versus status 1A pediatric heart transplant patients not transplanted with ventricular assist device support. Pediatric heart transplant patients (n=106) bridged to transplantation with EXCOR were compared with a similarly aged cohort (n=1021) within the Organ Procurement and Transplant Network (OPTN) database (both cohorts from May 2007 to December 2010). In the EXCOR group, 12-month post-transplant survival (88.7%) was similar to OPTN patients listed status 1A who were not on ventricular assist device support at transplant (89.3%; P=0.85) and significantly better than 12-month survival in OPTN patients on extracorporeal membrane oxygenation at transplant (60.3%; P<0.001). Rejection (50%) was a significantly (P=0.005) higher cause of 12-month post-transplant mortality in the EXCOR compared with the OPTN group. Death after transplant was also higher in EXCOR patients with congenital heart disease compared with those with cardiomyopathy (26.1% versus 7.2%; P=0.02). Post-transplant survival was similar in EXCOR patients with ≥1 serious adverse event during ventricular assist device support as those without an event during support. The 12-month post-transplant survival with EXCOR is comparable with overall pediatric heart transplant survival and superior to survival after extracorporeal membrane oxygenation. Neither adverse events during support nor factors associated with mortality during support influence post-transplant survival. Rejection was a significantly greater cause of post-transplant mortality in EXCOR than in OPTN patients.
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ABSTRACT: Ventricular assist devices (VADs) are increasingly being used as a bridge to transplantation and have been implicated as a risk factor for allosensitization to human leukocyte antigens (HLA). We investigate the association between VAD and allosensitization to human leukocyte antigens (HLA) and major-histocompatibility-complex (MHC) class I-related Chain A (MICA) antigens. We considered all patients who received a VAD at our institution between 2000 and 2009; 89 of them had pre-VAD and post-VAD (≤6 months after implant) HLA antibody screening. A control group of non-VAD heart transplant candidates was constructed with at least 2 pre-transplant panel-reactive antibody (PRA) tests within 8 months. Two controls were randomly selected/VAD patient matched for year (n = 178). Patients and controls with available sera from these time-points were tested by Luminex/flow PRA single-antigen beads and by MICA antibody Luminex single-antigen beads. Medical records were reviewed for comparison of pre-transplant immunologic risk factors and post-transplant outcomes between the 2 groups. Compared with controls, VAD patients had greater Class I differences between peak and initial PRA (18% vs 0%, p < 0.0001) and higher peak PRA (24% vs 6%, p < 0.0001). The differences between the 2 groups in Class II were less pronounced than in Class I. Of patients who had single-antigen testing, VAD implantation was significantly associated with development of new HLA antibody specificities (Class I and/or Class II) post-VAD with an increase in calculated PRA (cPRA) post-VAD compared with controls (16% vs 0%, p < 0.0001). This risk was still present after adjusting for age, gender, pre-VAD PRA, transfusion and duration of follow-up in a multivariate analysis (p < 0.0001 and 0.02, respectively). There were no differences in development of MICA antibodies between the 2 groups (14% in both). There was no significant difference in the incidence of pre-transplant positive T-cell crossmatch, pre-transplant donor-specific HLA antibodies, rejection episodes or graft survival between the 2 groups. Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.
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