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Bortezomib, a proteasome inhibitor, offers effective desensitization in heart transplant candidates.. We reviewed our center's experience using bortezomib as desensitization therapy for highly sensitized patients to assess pre- and post-transplant outcomes. We assessed 43 HTx candidates 2010-2021 who were highly sensitized with cPRA greater than 50%, underwent bortezomib desensitization, and were subsequently transplanted. Enrolled patients received a course of up to four doses of bortezomib (1.3 mg/m2) over 2 weeks in conjunction with plasmapheresis. The efficacy of bortezomib was assessed by comparing the pre- vs post-desensitization therapy in cPRA, panel reactive antibodies to HLA Class I or Class II antigens, and reduction in immunodominant DSA via MFI. 1-year survival, 1-year freedom from antibody-mediated rejection (AMR), 1-year freedom from hyperacute rejection, 1-year freedom from hemodynamic compromise rejection, and 1-year freedom from the development of de novo DSA were also assessed. The average cPRA prior to bortezomib treatment was 94.5%. Bortezomib did not lower cPRA, Class I or Class II antibodies or lower the immunodominant antibody. However, these highly sensitized patients who underwent HTx had 95% 1-year survival, 76% freedom from 1-year AMR and 65% freedom from 1-year de novo DSA development. Side effects of bortezomib included thrombocytopenia and/or pancytopenia (43%), treated infection (28%) and self-limited neuropathy (12%). The use of bortezomib in highly sensitized patients does not appear to be clinically effective in lowering circulating antibodies prior to heart transplantation. However, its use may have contributed to acceptable post-transplant outcomes. [ABSTRACT FROM AUTHOR]

It has been reported from the ISHLT registry that women have less optimal outcome after heart transplantation (HTx) compared to men. It is not known whether this difference is due to rejection, NF-MACE, or decreased survival. Between 2010 and 2020, we assessed 1071 HTx patients and divided them by male and female sex. 309 females and 762 males were included in the study. Post-transplant outcomes included 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), 1-year freedom from rejection (acute cellular rejection [ACR], antibody-mediated rejection [AMR]), and 1-year freedom from de novo DSA production. Women were divided into two groups, sensitized (PRA >10%) or non-sensitized. When comparing women to men, women had similar survival, freedom from CAV, and freedom from NF-MACE, but significantly lower freedom from ATR, AMR, and de novo DSA production. Women who were sensitized had similar survival but lower freedom from rejection and DSA production compared to non-sensitized women. 26% of our female patients were sensitized. Major post-transplant outcomes are similar for women and men. However, sensitization may be the reason for more AMR in women but it does not affect short-term major outcomes. Longer follow-up and impact of these outcomes need to be assessed. [ABSTRACT FROM AUTHOR]

In the past, light chain (AL) amyloid has been associated with poor outcomes after heart transplantation (HTx), mainly due to its complicated course. Many AL amyloid patients will require stem cell transplant following HTx. It is not known whether these patients have acceptable outcomes after HTx. Between 2008 and 2020, we assessed all AL amyloid patients undergoing HTx. Patients were divided into those that required stem cell therapy and those that did not. Both groups were compared to age-matched control that did not have amyloid. Endpoints included 1-year survival, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejection (any treated rejection [ATR], acute cellular rejection [ACR], antibody-mediated rejection [AMR], biopsy-negative rejection [BNR]). There was no difference between AL amyloid patients with and without stem cell therapy in 1-year survival, or freedom from CAV, NF-MACE, or ATR. Compared to matched controls, post-transplant outcomes were similar. (See table.) In the current era, therapies for AL amyloid post-heart transplant appear successful with acceptable outcome compared to non-amyloid patients. AL amyloid is not a contraindication for heart transplantation. [ABSTRACT FROM AUTHOR]