Heart valves represent the pinnacle of design and durability. They open and close approximately 70 times per minute, 100,000 times per day, and about 3 billion times during a lifetime. Given their extensive usage, it is remarkable how rarely they fail. Valvular disease affects approximately 75 million people worldwide, leading to around 280,000 valve replacements annually. The exceptional performance of these cardiac components lies in their ability to repair daily wear and tear, a quality that surpasses any human-designed biological prosthesis. Moreover, their capacity for growth alongside the individual, prompts some centers to consider using living cardiac components as substitutes for prosthetic alternatives.
The lack of growth in prostheses and homografts poses a persistent challenge for most pediatric cardiac surgeons. Consequently, one often prioritizes valve repair and re-repair, even at the cost of prolonged ischemia times. A suboptimal repair is frequently deemed preferable to valve replacement in pediatric patients. When repair is not feasible, various solutions exist, yet none are entirely satisfactory. Mechanical or biological prostheses, each with distinct advantages and disadvantages, are available. Homografts—either homovital (procured directly from untreated cadavers) or cryopreserved (stored at –135°C for logistical distribution reasons)—serve as structural components in surgery without preserving cellular viability. However, homografts lack growth capacity, necessitating multiple reoperations in pediatric patients to replace them with larger grafts. Furthermore, the implantation of homografts is not without risks. Neonatal or infant aortic valve surgery using homografts carries a mortality rate of 40%, escalating to 49% in truncal valve surgeries and followed by a yearly mortality rate of 15%. Costs are another concern, with a homograft priced around $25,000 in the United States.
Developing bioprostheses capable of growth is the ultimate goal in pediatric cardiac surgery. Technological limitations currently hinder the creation of living biological prostheses, as cellular growth and differentiation must be programmed. Efforts to achieve this milestone have occasionally resulted in major biomedical research scandals, such as the Paolo Macchiarini’s case involving artificial trachea transplants. Conversely, the Ross procedure, which autotransplants the pulmonary root, has demonstrated that such grafts grow with the patient. While the valve leaflets exhibit good durability, the primary challenge is long-term neo-root dilation due to the exposure of pulmonary tissue to systemic pressure. The Ross procedure has two major drawbacks: it sacrifices the right side of the heart, requiring multiple interventions to address outflow tract obstruction using prostheses or homografts, and it is a highly complex surgery with neonatal mortality exceeding 25%.
An alternative solution involves transplanting a heart that grows with the patient, despite the need for immunosuppressive treatment. This approach is also limited by organ scarcity in this age group, resulting in long waiting lists, as well as the added morbidity associated with immunosuppressive therapy. Although the mortality rate for transplantation is lower than that of the Ross procedure at less than 5%, it rises to approximately 35–50% at 20 years due to coronary allograft vasculopathy, ultimately leading to ventricular dysfunction.
The advantages and challenges of the Ross procedure and cardiac transplantation have given rise to the concept of partial heart transplantation. This technique seeks to combine the benefits of both approaches while minimizing their disadvantages. Partial heart transplantation, also referred to as a living homograft, retains the growth and repair properties of these tissues. Similar to the Ross procedure, these tissues are devascularized and re-implanted without compromising biological viability. However, only the aortic homograft is transplanted, avoiding the drawbacks associated with pulmonary valve involvement and providing a true systemic-pressure aortic root. Unlike conventional transplantation, partial heart transplants would require less stringent immunosuppression and would not experience coronary vasculopathy since only valves, not vascularized myocardium, are transplanted. If immunosuppression were discontinued, the transplanted valves would revert to functioning as standard homografts. Consequently, partial heart transplantation could mitigate some long-term complications of orthotopic heart transplantation, such as the 12% incidence of Epstein-Barr virus-related lymphoproliferative disease and 6% incidence of severe renal dysfunction caused by calcineurin inhibitors within 10 years.
The availability of donors for partial heart transplantation exceeds initial expectations. Any orthotopic cardiac transplant donor could also serve as a partial transplant donor. Moreover, approximately one-third of pediatric patients undergoing heart transplantation have dilated cardiomyopathy, where ventricular failure rather than valvular dysfunction is the issue. The hearts explanted from these patients could be utilized for partial transplants. Each donor heart could potentially benefit multiple recipients, amplifying the domino effect of such transplants. Nevertheless, implementing this technique requires complex logistics. Conducting several domino transplants simultaneously, as demonstrated by hospitals such as Morgan Stanley and Duke Children’s, involves coordinating multiple teams across different hospitals, often necessitating air transport.
Significant questions remain regarding partial heart transplantation. Regulatory aspects must address whether these materials should be classified as biological products or organs. Coding systems for clinical and accounting purposes need to be established. Immunosuppressive regimens and acceptable ischemia times for these components must be defined. Ideal candidates for this type of surgery need to be identified. Additionally, the feasibility of using this technique for atrioventricular valve lesions and managing subvalvular apparatus in such cases remains to be explored.
COMMENTARY:
Dr. Rajab’s review article eloquently argues the need to incorporate partial heart transplantation into our therapeutic arsenal. By tracing the necessity for these tissues from experimental surgeries in the laboratory to initial clinical experiences, it highlights a field ripe for exploration. With growing heart transplant waitlists, innovative strategies to salvage organs or organ parts are imperative. Fortunately, Spain’s centralized National Transplant Organization (ONT) has vast experience coordinating simultaneous transplants. Integrating partial heart transplantation into ONT’s operations seems logistically feasible.
Who knows? In the future, xenotransplant-derived components might serve similar purposes. Until then, maximizing organ utilization, even through unconventional maneuvers like domino transplants—orthotopic transplantation in a dilated cardiomyopathy patient and using the dilated heart’s valves for another recipient—could be the way to go.
REFERENCE:
Rajab TK. Partial heart transplantation: Growing heart valve implants for children. Artif Organs. 2023 Oct 18. doi: 10.1111/aor.14664.
