Alloimmunosensitization in Left Ventricular Assist Device Recipients and Impact on Posttransplantation Outcome

Abstract

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.

Clinical outcomes in sensitized heart transplant patients bridged with ventricular assist devices

“… found that patients with LVADs did not have increased rejection episodes, allograft vasculopathy, or decreased survival after transplantation, as compared to non‐bridged patients. This is supported by larger reviews by the ISHLT, which found that LVAD patients had higher rates of sensitization (16.6% vs. 7.6%) but no differences in mortality . A more recent study by Shankar et al.…”

“…Pre‐orthotopic heart transplant (OHT) LVAD implantation is known to increase pre‐transplant PRA levels . Although it is well documented that women tend to have a higher pre‐transplant PRA levels than men, LVAD‐induced rise in PRA levels appears to affect both genders equally .…”

“…Early reports indicated that these elevated levels of antibodies were linked to poorer outcomes, notably graft rejection . More recent studies have indicated that this difference may not be as significant as previously stated . Other studies have noted a positive correlation between increased sensitization and antibody‐mediated rejection (AMR) episodes .…”

Heart Transplantation in the Era of the Left Ventricular Assist Devices

“…In the era of first generation LVAD support, reports indicated that these elevated levels of antibodies were linked to poorer outcomes, notably graft rejection. This association is less clear in modern studies; while some have indicated that this difference may not be significant, other studies have noted an increased level of antibody-mediated rejection in the setting of increased sensitization [52]. This remains an issue of considerable controversy.…”

Sensitization and desensitization of burn patients as potential candidates for vascularized composite allotransplantation

“…rituximab) or intravenous immunoglobulins (IVIG) target anti-HLA antibodies indirectly [20]. The trend of immunologically incompatible organ replacement with good short-term results is meanwhile widespread for kidney transplantations based on a broad understanding of the principles of sensitization and desensitization [28][29][30][31][32].…”