麻豆传媒

The newborn that received the world's first partial heart transplant in 2022 continued to do well a year later, according to a case report from the transplant team.

Born with type A2 persistent truncus arteriosus and irreparable truncal valve dysfunction, Owen Monroe received living tissue implants containing the aortic and pulmonary valves -- tissue that is expected to grow alongside the child.

The partial heart transplant valves did indeed continue to show "adaptive growth and excellent hemodynamic function" more than 1 year later, Joseph Turek, MD, PhD, MBA, of Duke University Medical Center in Durham, North Carolina, and colleagues .

The operation had been performed in the spring of 2022 and .

"The rationale for partial heart transplant is that pediatric heart transplants grow. Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime," the authors explained.

Currently, children with irreparable heart valve dysfunction can get surgery to get cadaver homografts every time they outgrow a heart valve implant. These frequent implant exchanges are required until an adult-sized valve can fit, as cadaver homografts lack the capacity for growth or self-repair.

"We are frequently encountered with children who have heart valves that are poorly formed with inadequate function. Left unrepaired these children would develop heart failure, have poor growth, and have impaired physical, social, and emotional development. While surgical approaches have improved tremendously over the last several decades, outcomes after valve repairs and replacements are too often not durable," commented Kevin Daly, MD, of Boston Children's Hospital.

Turek's group noted the poor clinical outcomes of this approach, citing the more than 50% mortality in infancy for those getting these truncal valve implants.

"In contrast, neonatal heart transplants have only 15% mortality in infancy because transplanted hearts grow," they said. "However, long-term outcomes of neonatal heart transplants are limited by inevitable ventricular dysfunction, with 50% mortality by 20 years."

It has been seen that when the entire heart is transplanted, it will grow at a normal rate as the child grows. "Thus, it seems to be logical to have that expectation in the case of partial transplantation," reasoned heart failure and transplant cardiologist Shriprasad Deshpande, MD, of Children's National Hospital in Washington, D.C., who was not part of Owen's transplant team.

He nevertheless emphasized that long term follow-up is needed to set expectations for these cases.

In their case report, Turek and colleagues said the donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect, then the coronary artery buttons were re-implanted and the right ventricular outflow tract was enlarged to transplant the pulmonary root. Altogether, ischemic time reached 395 minutes: cardiopulmonary bypass time 197 minutes, aortic cross-clamp time 135 minutes, and total operation time 389 minutes.

One hope for partial heart transplant is that it is an opportunity to use donor organs that would otherwise be wasted.

Owen's donated valves came from a 2-day-old girl whose delivery had been complicated with hypoxic-ischemic brain injury. Her heart had good valves but the muscle tissue was deemed too weak for full transplant. The heart was donated after cardiac death.

"There are around 50% of potential donor hearts that are currently discarded for various reasons. Using these hearts for such partial transplantation is an appropriate use of such precious resources. If this provides an important answer to neonatal valve pathologies, it will prove to be a major step forward," Deshpande told 麻豆传媒.

Even so, partial heart transplant has the drawback of relying on immunosuppression.

"In infant heart transplant recipients, the major long-term risks from immunosuppression are posttransplant lymphoproliferative disease caused by Epstein-Barr virus infection (12% by 10 years) and severe kidney dysfunction caused by calcineurin inhibitors (6% by 10 years). Importantly, stopping immunosuppression for a partial heart transplant would simply turn the implant into a nongrowing homograft," according to the case authors.

According to their case report, the newborn underwent a course of postoperative immunosuppressive therapies involving mycophenolate mofetil and solumedrol administered preoperatively, solumedrol repeated on release of the cross-clamp, then postoperative antithymocyte globulin given once for blood type incompatibility and repeated doses of solumedrol, mycophenolate mofetil, and tacrolimus.

More research guiding the need and use of immunosuppression in partial heart transplant is needed, Deshpande said. "One potential approach may be the use of low-grade immunosuppression and anti-inflammatory medications at the beginning, say for a year and slow discontinuation of the same," he suggested.

At least for now, "the authors have demonstrated that with the use of chronic immunosuppression, the valves remain functional and grow with their patient during the first year of life, a period of rapid growth and development for any child," according to Daly.

The baby's donor-derived cell-free DNA remained below 0.15% 12 weeks postoperatively, and anti-B titers remained low. The boy was extubated on postoperative day 6 and discharged on day 30, Turek's team reported.

Deshpande warned that transplant markers of tissue viability and rejection may need to be reassessed in partial heart transplants, as donor fraction cell-free DNA may not be sensitive enough for this vascular tissue and endothelial tissue.

"This donor-derived cell-free DNA test can identify the percentage of circulating non-self DNA fragments in the blood, however this test has been validated in heart and kidney transplantation but the threshold level for rejection concern in a partial heart transplant is unknown," Daly explained to 麻豆传媒.

He said that another important question is whether the vascular endothelium might become a chimera of donor cells and recipient cells over time, as suggested in solid organ transplantation.

"One fascinating question is, to what extent can this living, growing donor heart valve tissue be replaced by living, growing recipient tissue. If there is extensive replacement with recipient endothelium, this would be a wonderful outcome since the immune system would be less likely to reject the valves," Daly said.

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