Management of Sensitization During Mechanical Circulatory Support

Due to the limited availability of available organs, amongst other factors, approximately one half of people undergoing heart transplant have been bridged with some form of mechanical circulatory support (MCS). Circulating antibodies against specific human leukocyte antigens (HLA) in the recipient, known as sensitization, can limit availability of suitable donor organs, potentially leading to prolonged waiting time and negatively affecting post-transplant outcomes. Patients with durable mechanical circulatory support devices have also been found to have an increased incidence of sensitization, thought to be a result of the upregulation of cytokines and enhanced immunogenicity of the device, as well as from transfusion of blood products during implantation or while on device support. Prior United Network for Organ Sharing (UNOS) registry data has shown that elevated panel reactive antibody (PRA) levels (>25%) in those with left ventricular assist devices (LVADs) does not impact the incidence of treated rejection or survival in the first year after heart transplant, though there was a signal of higher rates of primary graft dysfunction (PGD). Sensitization remains an important barrier to heart transplantation and is heightened by durable mechanical circulatory support device therapy, which is increasingly being used as a bridge to transplant. Sensitization has been associated with an increased risk of rejection, coronary vasculopathy, and mortality after transplant. New therapeutic options in the management of sensitization are available both in the pre-transplant and peri-operative stages.