Partial heart transplantation for pediatric heart valve dysfunction: A clinical trial protocol

Abstract

Congenital heart defects are the most common type of birth defects in humans and frequently involve heart valve dysfunction. The current treatment for unrepairable heart valves involves valve replacement with an implant, Ross pulmonary autotransplantation, or conventional orthotopic heart transplantation. Although these treatments are appropriate for older children and adults, they do not result in the same efficacy and durability in infants and young children for several reasons. Heart valve implants do not grow with the. Ross pulmonary autotransplants have a high mortality rate in neonates and are not feasible if the pulmonary valve is dysfunctional or absent. Furthermore, orthotopic heart transplants invariably fail from ventricular dysfunction over time. Therefore, the treatment of irreparable heart valves in infants and young children remains an unsolved problem. The objective of this single-arm, prospective study is to offer an alternative solution based on a new type of transplant, which we call “partial heart transplantation.” Partial heart transplantation differs from conventional orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. Similar to Ross pulmonary autotransplants and conventional orthotopic heart transplants, partial heart transplants contain live cells that should allow it to grow with the recipient child. Therefore, partial heart transplants will require immunosuppression. The risks from immunosuppression can be managed, as seen in conventional orthotopic heart transplant recipients. Stopping immunosuppression will simply turn the growing partial heart transplant into a non-growing homovital homograft. Once this homograft deteriorates, it can be replaced with a durable adult-sized mechanical implant. The protocol for our single-arm trial is described. The ClinicalTrials.gov trial registration number is NCT05372757.

Animal models for partial heart transplantation

“…Viable cells allow the transplant to grow with the child. 12 Partial heart transplants also differ from heart transplants because the native ventricles are spared. Sparing the native ventricles avoids the most serious complications of heart transplants, namely chronic rejection causing ventricular dysfunction.…”

Growing Heart Valve Implants for Children

“…Researchers have published a clinical trial protocol for a prospective single-arm pilot trial to determine the feasibility and safety of PHT as well as analysis of valve annulus growth and evidence of valve regurgitation or stenosis. This trial will be performed on infants and children less than 2 years old in need of semilunar heart valve transplant [36].…”

Outcomes of truncal valve replacement in neonates and infants: a meta-analysis

“…Due to the scarcity of donor organs, transplantation will not always be feasible. 42 Recently, surgeons have corrected truncus arteriosus with severe truncal valve insufficiency by performing a partial heart transplantation, 43,44 wherein the pulmonary and aortic roots of a donor heart otherwise unsuitable for orthotopic heart transplantation were used to perform the primary repair. The patient remained alive after over 6 months, and echocardiographic measurements show that the transplanted valves have grown with the patient.…”