Approximately 1% of children are born with a heart defect. Many clinically important heart defects affect the semilunar valves. Semilunar valve defects that cannot be repaired require valve replacement. At birth, the aortic and pulmonary valves average only 7 and 9 mm respectively. This is much smaller than any available prosthetic heart valve. Therefore, these valves are typically replaced with homografts. Homografts are procured from human cadavers using a process that does not preserve cellular viability. Without viable cells, homografts are unable to grow or repair wear and tear.1 This commits children with homografts to serial implant exchanges. The aortic valve can also be replaced using the Ross procedure. The Ross procedure involves auto-transplantation of the patient’s own pulmonary valve into the aortic position, followed by implantation of a homograft into the pulmonary position. The rationale for the Ross procedure is that pulmonary autografts contain viable cells, which allow them to grow and repair wear and tear.1 This decreases the number of lifetime reoperations because homografts in the low-pressure pulmonary position have greater longevity than in the aortic position. However, pulmonary autografts in the high-pressure aortic position tend to dilate over time. This risks leaving affected children with pathological valves in both the aortic and pulmonary positions. Furthermore, the Ross procedure is not suitable for treating heart defects with dysfunctional pulmonary valves, such as truncus arteriosus, or tetralogy of Fallot. To solve these problems, there is a clinical need for growing heart valve substitutes.
Partial Heart Transplantation
Partial heart transplantation is a new procedure that delivers growing heart valve substitutes.2 The rationale for partial heart transplantation is that the valves contained in heart transplants grow.3 Partial heart transplants differ from heart transplants because only the part of the heart containing the necessary valve is transplanted. In theory, this could be achieved using a range of surgical techniques. In practice, surgical techniques for partial heart transplantation to date have been based on techniques for homograft semilunar valve replacement.4 Partial heart transplants differ from homografts because the grafts are ABO typed, ischemia times are controlled, and recipients are immunosuppressed to preserve graft cellular viability. Viable cells allow partial heart transplants to grow, and presumably repair wear and tear.4 Unlike the Ross procedure, partial heart transplants do not require harvesting the native pulmonary valve. This avoids the risk of valve pathology in both the aortic and pulmonary positions and allows for treating heart defects with dysfunctional pulmonary valves. However, experience with heart transplantation shows that recipient immunosuppression adds risk. Therefore, competing risks may favor valve repair or the Ross procedure over partial heart transplantation when feasible. Furthermore, partial heart transplantation depends on the availability of donor hearts. Donor hearts are a scarce resource with alternative use in heart transplantation. Unlike heart transplants, partial heart transplants can utilize donor hearts with ventricular dysfunction. Not only does this increase the pool of transplantable donor hearts, but it also allows for domino partial heart transplantation using cardiectomy hearts from heart transplant recipients.5 Moreover, donor hearts can be partitioned to provide multiple partial heart transplant grafts with different valves. These strategies amplify the utility of each donor heart to benefit a cascade of recipients.
Transition from Experimental Research to Innovative Practice
New procedures such as partial heart transplantation occur at the boundary between experimental research and innovative practice. According to the Belmont Report, new procedures constitute experimental research if they are undertaken to test a hypothesis that contributes generalizable knowledge. In contrast, new procedures that are undertaken solely to treat individual patients with a reasonable expectation of success constitute innovative practice. Partial heart transplantation transitioned from the realm of experimental research into the realm of innovative practice through application of the scientific method. First, the observations that heart valves contained in heart transplants grow despite allotransplantation and that Ross autografts grow despite valve excision and reimplantation were synthesized into the hypothesis that partial heart transplants would grow despite allotransplantation, valve excision and reimplantation.2 Next, this hypothesis was tested in animal models. Finally, success in the swine model turned partial heart transplantation from an experimental procedure designed to test a hypothesis into an innovative procedure suitable for clinical implementation.
State-of-the-Art for Partial Heart Transplantation
Clinical teams proficient in heart transplantation, the Ross procedure and homograft valve replacement are well-positioned to implement partial heart transplantation because partial heart transplants closely resemble these procedures from a medical and surgical perspective respectively. To date, several independent clinical teams have successfully performed partial heart transplantation to treat children with a wide range of heart defects including truncus arteriosus, congenital aortic stenosis, tetralogy of Fallot with pulmonary atresia, and transposition of the great arteries with ventricular outflow tract obstruction.4,5 Management of these children has been guided by clinical protocols for heart transplantation.4 Unlike heart transplants, partial heart transplants spare the ventricles. Sparing the ventricles eliminates important mechanisms of graft failure, such as primary graft dysfunction and allograft vasculopathy. This has led some clinical teams to deviate from standard protocols for heart transplantation by increasing the accepted graft ischemia time from hours to days and reducing immunosuppression from multi-drug regimen to tacrolimus monotherapy. Sparing the ventricles also eliminates the ability to biopsy the grafts. Therefore, partial heart transplant rejection is monitored using donor-derived cell-free DNA, and donor-specific antibodies. Partial heart transplant growth is monitored by echocardiography. Early and mid-term follow-up for up to 2 years has confirmed that partial heart transplants grow normally with recipient children.
Future Directions
Future development of partial heart transplantation should focus on three pivotal areas. First, clinical research should assess partial heart transplant outcomes for each of its possible indications. Notably, heart transplants virtually never fail from valve dysfunction. Consequently, long-term outcomes of partial heart transplants are expected to be excellent.3 Second, fundamental research should elucidate how the biology of partial heart transplantation differs from the biology of heart transplantation. Clinical translation of this knowledge will contribute evidence-based protocols optimized for partial heart transplantation. Optimal protocols for partial heart transplant graft preservation, recipient immunosuppression, and rejection monitoring are expected to differ substantially from protocols for heart transplantation because graft ventricular function is no concern. Third, surgeons should explore the design space for partial heart transplantation to broaden its clinical applications beyond semilunar valve replacement. For example, our preclinical data suggests that growing surgical patches made from transplanted cardiovascular tissue could improve the outcomes of pulmonary vein repair, atrioventricular valve repair, and branch pulmonary artery reconstruction.
Acknowledgements
Dr. Rajab acknowledges research support for partial heart transplantation from the NIH (R41 HL169059), the American Association for Thoracic Surgery, and Arkansas Children’s Research Institute.
Footnotes
Conflicts of Interest Disclosures
None
References
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