Effect of left ventricular assist device implantation on complement activation of the cardiac allograft in the early post-heart transplant course

Background: The use of mechanical circulatory support (MCS) is increasing and approximately 40% of patients undergoing heart transplantation (HTx) are transplanted from MCS. Possible effects of MCS in terms of allosensitation are of growing importance in the routine diagnostic workup for antibody-mediated rejection in cardiac allografts.

Purpose: We investigated the hypothesis that pretransplant use of MCS is associated with intramyocardial capillary C4d depositions in the cardiac allograft.

Methods: We evaluated endomyocardial biopsies (EMBs) of 35 consecutive pts who underwent HTx between 02/2014–07/2017 (m=23, f= 12, age range 19–71 yrs, mean age 54 yrs). Same sex donor/recipient matched HTx was performed in 17 male pts and 13 female pts. (age range of donors 19–61 yrs, mean 41.5 yrs). There were 12 patients (f=2) with MCS treatment (HMII) prior to heart transplantation (MCS group) and 23 patients (f=11) without MCS treatment (non-MCS group).

EMBs harvested at time of HTx, and after 6 and 12 month were evaluated. The diagnostic workup included conventional histology and immunohistochemistry (C4d) on formalin-fixed paraffin-embedded tissue sections. The presence of peritransplant injury in the donor biopsy and differences in C4d depositions, which were reported in 10 percent ranges of positive capillaries between groups, were analyzed with ANCOVA.

Results: While there was a significant difference in C4d deposition at 6 month post HTx between the overall MCS group and the non-MCS group (p=0.019), (range of capillary C4d depositions between 0–30%), the MCS patients did not show an increase in C4d depositions (p=0.183) at 12 month post Htx (range of capillary C4d depositions between 0–60%). Recipient age did not influence the effect of MCS on early or late C4d deposition.

Conclusion: Our results suggest that MCS treatment may influence the outcome of cardiac allografts with regard to complement activation in the early post-transplant period, which may in MCS patients be related to allosensitation to the MCS device or different use of blood products in MCS and non-MCS patients.