2025 HFSA Contemporary Issues in Heart Failure - OnDemand-Desensitization Strategies

Video Transcription

Video Summary

Dr. Mount Sinai Health System's Heart Failure and Transplantation System Lead discusses desensitization strategies to reduce circulating alloantibodies in heart transplant candidates. Allosensitization, caused by pregnancy, transfusions, or prior transplants, leads to circulating HLA antibodies and affects 10-20% of transplant candidates, increasing wait times and rejection risks. Sensitization is measured via assays detecting specific antibodies, particularly using solid-phase techniques quantifying mean fluorescent intensity (MFI). High sensitization (CPRA >50%) motivates desensitization, although approaches remain controversial due to risks like infection and cost.<br /><br />Detection includes complement-binding assays (C1q) and dilution studies to quantify antibody levels. Desensitization strategies target antibody removal via plasmapheresis or neutralization through IVIG, B-cell depletion (rituximab), proteasome inhibition to eliminate plasma cells (bortezomib/carfilzomib), and co-stimulation blockade (belatacept). Tocilizumab, an IL-6 inhibitor, modulates immune response towards tolerance. New investigational therapies like M. lipidase rapidly cleave IgG antibodies. Liver transplant prior to heart transplant (HALT) utilizes the liver's antibody clearing capacity. Eculizumab inhibits complement-mediated injury, lowering rejection incidence.<br /><br />No single desensitization method is superior; combination therapies tailored to patient profiles show promise. Overall, desensitization aims to expand donor pools, reduce wait time, and improve transplant outcomes despite ongoing challenges and risks.

Keywords

heart transplant desensitization

alloantibodies

HLA antibodies

plasmapheresis

IVIG therapy

rituximab

complement-binding assays