Biopsy-diagnosed antibody-mediated rejection based on the proposed International Society for Heart and Lung Transplantation working formulation is associated with adverse cardiovascular outcomes after pediatric heart transplant

Everitt, Melanie D.; Hammond, M. Elizabeth H.; Snow, Greg; Stehlik, Josef; Revelo, Mônica P.; Miller, Dylan V.; Kaza, Aditya K.; Budge, D.; Alharethi, Rami; Molina, Kimberly; Kfoury, Abdallah G.

doi:10.1016/j.healun.2012.03.009

Cited by 45 publications

(32 citation statements)

References 29 publications

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“…This is further confounded by the evolution of HLA antibody detection technology and the increasing surveillance and detection of DSA as discussed above. Retrospectively assigning the ISHLT pathologic AMR (pAMR) grades in a single center review showed pAMR2 or higher in 18% of biopsies and 59% of patients; pAMR3 was associated with worse cardiovascular outcomes (46). Using a cohort of patients from 2010-2014 to look at AMR in a more recent era, an analysis from PHTS showed an incidence of treated AMR of 12% in the first 3 years postheart transplant with risk factors including a diagnosis of coronary heart disease (CHD), sensitization, a positive crossmatch, severe ACR, and the use of maintenance steroids (40).…”

Section: Antibody Mediated Rejectionmentioning

confidence: 99%

Current state of pediatric cardiac transplantation

Dipchand

2018

Ann. Cardiothorac. Surg.

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Pediatric heart transplantation is standard of care for children with end-stage heart failure. The diverse age range, diagnoses, and practice variations continue to challenge the development of evidence-based practices and new technologies. Outcomes in the most recent era are excellent, especially with the more widespread use of ventricular assist devices (VADs). Waitlist mortality remains high and knowledge of risk factors for death while waiting and following transplantation contributes to decision-making around transplant candidacy and timing of listing. The biggest gap impacting both waitlist and overall survival remains mechanical support options for infants and patients with single ventricle physiology. Though acute rejection has decreased progressively, both diagnosis and management of antibody-mediated rejection has become increasingly challenging and complex, as has the ability to understand the implication of anti-HLA antibodies detected both pre-and post-transplantation-including when and how to intervene. Trends in immunosuppression protocols include more use of induction therapy and steroid avoidance or withdrawal protocols. Common long-term morbidities include renal insufficiency, which can be mitigated with surveillance and renal-sparing strategies, and infections. Functional outcomes are excellent, but significant psychosocial challenges exist in relation to neurodevelopment, non-adherence, and transition from childcentered to adult-centered care. Cardiac allograft vasculopathy (CAV) remains a barrier to long-term survival, though it is more apparent that objective evidence of an impact on the allograft is important with regards to impact on outcomes. Retransplantation is rare in pediatric heart transplant recipients. Pediatric heart transplantation continues to evolve in order to address the challenges of the diverse group of patients that reach end-stage heart failure during childhood.

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Section: Antibody Mediated Rejectionmentioning

confidence: 99%

Current state of pediatric cardiac transplantation

Dipchand

2018

Ann. Cardiothorac. Surg.

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“…In the IHSLT registry, AMR of pathological Grade 2 or higher was present in 18% of protocol endomyocardial biopsies, representing 59% of patients (28). Patients with Grade 3 AMR had more cardiac allograft vasculopathy and increased cardiovascular mortality.…”

Section: Introductionmentioning

confidence: 99%

Long-term outcomes of children after solid organ transplantation

Kim

Marks

2014

Clinics

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Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation.

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“…The association of AMR with cardiovascular mortality, such as death resulting from acute rejection, myocardial infarction, congestive heart failure, graft failure, arrhythmia or CAD, was recently shown in paediatric HTx [7]. Such an observation supports protocol screening for AMR.…”

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confidence: 62%