Effect of cardiac graft rejection on semilunar valve function: implications for heart valve transplantation

Abstract

Background: The treatment of neonates with unrepairable heart valve dysfunction remains an unsolved problem because there are no growing heart valve replacements. Heart valve transplantation is a potential approach to deliver growing heart valve replacements. Therefore, we retrospectively analysed the semilunar valve function of orthotopic heart transplants during rejection episodes. Methods: We included children who underwent orthotopic heart transplantation at our institution and experienced at least one episode of rejection between 1/1/2010 and 1/1/2020. Semilunar valve function was analysed using echocardiography at baseline, during rejection and approximately 3 months after rejection. Results: Included were a total of 31 episodes of rejection. All patients had either no (27) or trivial (4) aortic insufficiency prior to rejection. One patient developed mild aortic insufficiency during a rejection episode (P = 0.73), and all patients had either no (21) or trivial (7) aortic insufficiency at follow-up (P = 0.40). All patients had mild or less pulmonary insufficiency prior to rejection, which did not significantly change during (P = 0.40) or following rejection (P = 0.35). Similarly, compared to maximum pressure gradients across the valves at baseline, which were trivial, there was no appreciable change in the gradient across the aortic valve during (P = 0.50) or following rejection (P = 0.42), nor was there any meaningful change in the gradient across the pulmonary valve during (P = 0.55) or following rejection (P = 0.91). Conclusions: This study demonstrated that there was no echocardiographic evidence of change in semilunar valve function during episodes of rejection in patient with heart transplants. These findings indicate that heart valve transplants require lower levels of immune suppression than orthotopic heart transplants and provide partial foundational evidence to justify future research that will determine whether heart valve transplantation may deliver growing heart valve replacements for children.

Partial Heart Transplant in a Neonate With Irreparable Truncal Valve Dysfunction

“…Immunosuppression for partial heart transplants is based on immunosuppression for pediatric heart transplants, because the valves contained in pediatric heart transplants are known to grow . It can be less stringent because the valves in heart transplants are spared from rejection . The long-term risks from immunosuppression are predictable based on the experience with pediatric heart transplants.…”

Partial Heart Transplantation in Adult Cardiac Surgery

“…Evidence in favor of this conclusion includes the observation that the valves in rejected OHTs retain their functional and structural integrity even after failure of the graft as a whole. 8,[31][32][33] Other studies on the cellular level demonstrated decreased or no antigenicity of the aortic valve when compared with the cardiac endothelium. 34,35 In a study of transplanted porcine hearts, Chen et al showed that while the donor heart is rejected due to IgM antibodies against the galactose α-1,3-galactose antigen that is strongly expressed on the cardiac endothelium, this antigen was not present on porcine aortic or pulmonary valves.…”

Partial heart transplantation: Growing heart valve implants for children

“…Firstly, heart valves appear to enjoy a degree of immune privilege 84,85 . For example, the outflow valves of orthotopic heart transplants are histologically 12,36 and functionally 86 spared from rejection. Secondly, the risk from an immune response to a partial heart transplant is far less than the risk of an orthotopic heart transplant.…”