Our data showed no difference in the overall post-heart transplant survival and freedom from acute cellular and antibody-mediated rejection between anti-AT1R-negative and anti-AT1R-positive recipients. Further research is needed to assess the role of anti-AT1R antibodies in the risk stratification of LVAD-bridged recipients on the post-heart transplantation outcomes.
SummarySolid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panelreactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.
Left ventricular assist devices (LVADs) have become an established surgical therapy for patients with end-stage heart failure who require hemodynamic support as a bridge-to-transplant or destination therapy. However, the anatomic and physiologic consequences of long-term LVAD support have yet to be fully clarified. Despite the clinical success of these devices, it has been reported that many patients bridged to transplantation with mechanical support develop circulating antibodies with potential donor reactivity. Transplanting against existing or historic donor-specific antibodies is associated with increased risk of antibody-mediated rejection, graft dysfunction, and decreased survival. Safe transplantation of allosensitized patients is dependent on using prospective crossmatching and antibody titer reduction techniques (desensitization). Strict protocols requiring a negative prospective crossmatch before transplantation result in a decreased donor pool and a longer duration of support in sensitized LVAD recipients with increased inherent morbidity such as infections and thromboembolic complications. The aim of this review is to present the current state of knowledge of possible immunologic mechanisms involved in alloimmunization of LVAD recipients, outline new methods of antibody detection, compare various desensitization strategies, and present an overview of clinical data assessing the impact of sensitization on posttransplantation outcome.
Serial measurement of BNP in outpatients with LVAD correlates with the occurrence of adverse events. Assessment of absolute values of BNP peak seems to have a similar accuracy to analysis of intra-individual variation of BNP and it is more practical.
Evidence regarding the use of bortezomib-containing schemes in primary treatment of antibody-mediated rejection in heart transplant recipients is scarce. This case report presents the clinical experience with upstream use of bortezomib in primary treatment of early antibody-mediated rejection in an adult heart transplant recipient. Two cycles of bortezomib together with methylprednisolone, immunoadsorption, rituximab, and supplementary doses of intravenous immunoglobulin G reversed signs of heart failure, production of donor-specific antibodies, and findings of antibody-mediated rejection in biopsy. This treatment regimen was tolerated with only mild hematologic toxicity and proved to be successful during a 12-month follow-up. Primary treatment with a bortezomib-containing regimen appears to be a new therapeutic option for severe antibody-mediated rejection in heart transplant recipients. However, the efficacy and safety of this treatment need to be tested in prospective trials.
, Peter Ivak a , Ivan Netuka a Aims. One of the proposed limitations of left ventricular assist device (LVAD) therapy is high degree of sensitization. Apart from human leukocyte antigen (HLA), antibodies against Angiotensin II Type 1 Receptor (AT1R) have been associated with adverse outcomes. The purpose of this study was to compare complications and survival of anti -AT1R positive versus negative Heart Mate II (HMII) recipients. Methods. Altogether 96 patients received HMII at our institution between 2008 and 2012. These were stratified into three groups: antibody positive before implantation (AT1R+), antibody conversion during support (AT1R-/+) and patients who remained antibody negative (AT1R-). Survival, major on-device adverse events and post-transplant rejections were assessed with Kaplan-Meier and log-rank tests.Results. Two year on-device and overall survival was 78 ± 12% and 75 ± 10% in AT1R-, 60 ± 23% and 60 ± 15% in AT1R+ and 92 ± 6% and 87 ± 5% in AT1R-/+ group (P = 0.409, P = 0.185). Freedom from major adverse event at two years for AT1R-, AT1R+ and AT1R-/+ was 49 ± 14%, 53 ± 16% and 41 ± 11% (P = 0.875). Freedom from rejection was 63 ± 17% in patients who were both anti-AT1R and HLA negative and 65 ± 13% in those who were antibody positive (P = 0.788). Conclusion.Patients who were anti-AT1R antibody positive had similar on-device survival and rate of complications in comparison to those who were antibody negative. In transplanted patients, there were no differences in the overall survival and rejection between the groups.
(patients > 18 and < 18 years of age, respectively). Time to > 50% reduction in GFR was then compared in a uni-and multivariate Cox regression model between the patients with and without proteinuria. In the multivariate model, adjustments were made for previously identified risk factors for CKD after HT, including age, sex, hypertension and diabetes mellitus. P < 0.05 was considered statistically significant. Results: Data from urine test strips was available in 79 patients, out of which 13 were positive for proteinuria. 1 year after HT, median GFR was 53 (range 20-81) vs. 56 (range 28-111) mL/min/1.73m2 in patients with and without proteinuria, respectively, at this time point (p= 0.28). In the Cox-regression analysis, proteinuria the first year after HT was related to a higher rate of GFR-decline, with a hazard ratio (95% confidence interval, p-value) of 2.46 (1.04-5.82, p= 0.04) and 5.15 (1.23-21.55, p= 0.03) in the uni-and multivariate model, respectively. Conclusion: Our results indicate that proteinuria the first year after HT is a predictor of GFR-decline. Special attention should therefore be given to patients with proteinuria early after HT. Larger multicenter studies including more patients are encouraged to verify the results of the present study.
Background: Cytomegalovirus (CMV) is a major cause of infection in the early period after heart transplantation (HTx). There are limited data comparing universal prophylaxis with preemptive treatment of CMV infection in HTx recipients. Therefore, the goal of this study was to evaluate efficacy and safety of both strategies. Methods: A total of 17 HTx recipients were prospectively enrolled in the universal prophylaxis group. This study cohort was matched with 18 HTx recipients who had the same immunosuppressive regimen and received preemptive therapy for CMV infection. All patients were CMV-seropositive. The study group received oral valganciclovir in a dose of 900 mg daily for 100 days. The second group was treated in case of CMV viraemia higher than 500 copies/ml. The incidence of CMV infection, other opportunistic infections and acute graft rejection and adverse events were evaluated at 3 th , 6 th and 12 th months post-transplant. Results: Universal prophylaxis was well tolerated in 87.5% of the patients for a period of 100 days. Leukopenia was the most frequent side-effect that appeared in 25% of this group. This strategy decreased the rate of asymptomatic CMV infection during the first three months after HTx (11.7% vs 55.6%, p = 0.006) compared with preemptive therapy. This positive effect was associated with lower incidence of acute graft rejection at 12 months of follow up (6.3% vs 41.2%, p = 0.015). Conclusion:Universal prophylaxis with valganciclovir in CMV-seropositive HTx recipients was acceptably safe and compared with preemptive therapy of CMV infection reduced the incidence of asymptomatic CMV infection and of acute graft rejection. SOUHRNKontext: Cytomegalovirus (CMV) je jedním z hlavních původců infekce v časném pooperačním období po transplantaci srdce (OTS). V současnosti existují pouze omezená data srovnávající univerzální profylaxi s preemptivní terapií CMV infekce u pacientů po OTS. Cílem naší prospektivní studie bylo posoudit účinnost a bezpečnost obou metod. Metody: Do skupiny s univerzální profylaxí bylo zařazeno celkem 17 příjemců OTS. Kontrolní skupinu tvořilo 18 pacientů, kterým byla podána preemptivní terapie. Všichni pacienti měli zavedenou stejnou imunosupresivní léčbu a byli CMV sérologicky pozitivní. Za účelem univerzální profylaxe byl podán perorální valganciclovir v dávce 900 mg denně po dobu 100 dnů. Ve skupině s preemptivní terapií byla zahájena léčba
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