Assessment and management of allosensitization following heart transplant in adults

Jaiswal, Abhishek; Bell, Jennifer J.; DeFilippis, Ersilia M.; Kransdorf, E.; Patel, J.; Kobashigawa, Jon A.; Kittleson, M.; Baran, David A.

doi:10.1016/j.healun.2022.12.011

Cited by 5 publications

(4 citation statements)

References 73 publications

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“…Development of DSA is frequently observed after HTx as approximately 25%–30% of patients develop de‐novo DSA within five years from HTx. The majority of these de‐novo DSAs are directed against HLA class II followed by a mixture against HLA class I and II 17–19 . In accordance with these data, we detected de‐novo DSA in 25% of our patients, mainly directed against HLA class II.…”

Section: Discussionsupporting

confidence: 90%

“…The majority of these de-novo DSAs are directed against HLA class II followed by a mixture against HLA class I and II. [17][18][19] In accordance with these data, we detected de-novo DSA in 25% of our patients, mainly directed against HLA class II. However, the DSA presence is not diagnostic for AMR and the true AMR incidence is unknown.…”

Section: Frequency Of Dsa and Amrsupporting

confidence: 91%

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Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Clemmensen,

Hjort Baatrup,

Bjerre

et al. 2024

Clinical Transplantation

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BackgroundWe aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality.MethodsThe study population comprises 193 consecutive long‐term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow‐up or right censuring on the 30th of June 2023.ResultsDSAs were detected in 50 patients using a cut‐off at MFI ≥1000 and 45 patients using a cut‐off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0–14.4]. DSA positive patients had poorer graft function and higher values of NT‐proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow‐up of five years [4.7–5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI .6–2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5–4.8)ConclusionsRoutine screening reveals DSA in approximately 25% of long‐term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.

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Section: Discussionsupporting

confidence: 90%

Section: Frequency Of Dsa and Amrsupporting

confidence: 91%

Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Clemmensen,

Hjort Baatrup,

Bjerre

et al. 2024

Clinical Transplantation

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“…In our study cohort, class 2 DSA positivity was a relatively common occurrence (21%), 8,11,19,20,[50][51][52] while HTx patients with both class 1 and 2 DSA positivity was much less frequent (6%). 53 Furthermore, we found that patients who were both class 1 and 2 DSA positive were at a significantly increased risk for being in the C4d+/DSA+ rather than C4d-/DSA+ group.…”

Section: Discussionmentioning

confidence: 66%

Donor-Specific Antibody Testing is an Effective Surveillance Strategy for High-Risk Antibody Mediated Rejection in Heart Transplant Patients in the Contemporary Era

Cusi,

Cardenas,

Tada

et al. 2023

Preprint

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BackgroundC4d immunostaining of surveillance endomyocardial biopsies (EMB) and testing for donor specific antibodies (DSA) are routinely performed in the first year of heart transplantation (HTx) in adult patients. C4d and DSA positivity have not been evaluated together with respect to clinical outcomes in the contemporary era (2010–current).MethodsThis was a single center, retrospective study of consecutive EMBs performed between November 2010 and April 2023. The primary objective was to determine whether history of C4d and/or DSA positivity could predict death, cardiac death, or retransplant. Secondary analyses included cardiac allograft dysfunction and cardiac allograft vasculopathy. Cox proportional hazards models were used for single predictor and multipredictor analyses.ResultsA total of 6,033 EMBs from 519 HTx patients were reviewed for the study. There was no significant difference (p = 0.110) in all-cause mortality or cardiac retransplant between four groups: C4d+/DSA+, C4d+/DSA-, C4d-/DSA+, and C4d-/DSA-. The risk for cardiac mortality or retransplant was significantly higher in C4d+/DSA+ versus C4d-/DSA-patients (HR = 4.73; pc= 0.042) but not significantly different in C4d+/DSA- versus C4d-/DSA- patients (pc= 1.000). Similarly, the risk for cardiac allograft dysfunction was significantly higher in C4d+/DSA+ versus C4d-/DSA- patients (HR 3.26; pc= 0.001) but not significantly different in C4d+/DSA- versus C4d-/DSA- patients (pc= 1.000). Accounting for nonadherence, C4d/DSA status continued to predict cardiac allograft dysfunction but no longer predicted cardiac death or retransplant.ConclusionsMedically adherent C4d+/DSA+ HTx patients show significantly greater risk for cardiac allograft dysfunction but not cardiac mortality or retransplant. In contrast, C4d+/DSA- patients represent a new immunopathologic group with a clinical course similar to that of HTx patients without antibody mediated rejection.

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“…However, implementing allosensitization into allocation strategies has some challenges, including heterogeneity among allosensitization data due to differences in thresholds and standards among HLA laboratories. 26) To improve waiting list mortality and post-transplantation outcomes in sensitized patients, further consensus is necessary regarding the use of allosensitization in allocation policies among transplantation societies, including HLA specialists.…”

Section: Discussionmentioning

confidence: 99%

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data

Kim,

Choi,

Cho

et al. 2024

Korean Circ J

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Author's summary The prevalence of sensitized patients waiting for heart transplantation (HTx) is increasing. We assessed the prevalence and clinical impact of panel-reactive antibody (PRA) in patients undergoing HTx using real-world, nationwide, multi-center data. Among patients who underwent HTx during 2014–2021, 19.8% (n=161) had calculated PRA (cPRA) ≥50%. A total of 61 patients underwent desensitization treatment before HTx. More patients with cPRA ≥50% had significantly higher positive flow cytometry crossmatch at HTx and preformed donor-specific antibody than those with cPRA <50%. During follow-up, patients with cPRA ≥50% had significantly lower freedom from antibody-mediated rejection, but the overall survival rate was comparable to those with cPRA <50%.

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Assessment and management of allosensitization following heart transplant in adults

Cited by 5 publications

References 73 publications

Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?

Donor-Specific Antibody Testing is an Effective Surveillance Strategy for High-Risk Antibody Mediated Rejection in Heart Transplant Patients in the Contemporary Era

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data

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