There is a critical shortage of donated hearts for children. Every year, roughly 50 children in Canada are on the waitlist for a heart transplant, and roughly 20-25 will be left waiting. Currently, the only hearts accepted for paediatric donation are from donors who suffer brain death; it was previously thought that donors whose hearts stopped (cardiac death) could not offer viable organs for transplantation. However, thanks to investments from the James H. Cummings Foundation, SickKids is on the cusp of increasing the number of viable donated hearts via Dr. Osami Honjo’s Death After Cardiac Death (DCD) Transplant Research Project.
In the first phase of this project, Dr. Honjo and his team developed the world’s first paediatric ex-vivo perfusion machine to recover a heart from a DCD donor. By circulating warm oxygenated blood, the machine can reanimate and sustain a DCD heart for transplantation. Perfusion machines exist for other organs and are in limited use for adults. The goal is to advance this technology for infant hearts. The second project phase was to test the prototype on animal models. Positive results have paved the way for trials on human hearts. The team also conducted several studies of two drugs that prevented cell damage and edema (swelling) during perfusion. The next phase of the project involves three core goals over the next three years: 1) Conduct the world’s first human trial of a paediatric DCD transplant; 2) Design and develop a novel biventricular ex-vivo perfusion device; and 3) A study to determine maximal time of donor heart viability: what length of ischemic time is too long?
Thanks to another generous investment from the James H. Cummings Foundation in early 2024, Dr. Osami and his team have funding to design and develop a biventricular ex-vivo perfusion machine (goal #2) that can support both chambers of the heart, and thus, higher-risk hearts. This is a ground-breaking project to design and develop a new ex-vivo perfusion machine that can support both chambers of the heart, the right and left – a novel innovation in paediatrics. Current commercial devices support only the left chamber. But right-heart failure of the transplanted heart also greatly influences whether patients survive and can safely go home after surgery. The new perfusion machine would be able to better support and test high-risk hearts that have been without blood flow longer. This all works toward the overarching goal of expanding the pool of donor hearts and reducing the number of patients on the waitlist. The team is in the preliminary design phase of the biventricular ex-vivo perfusion system. It will initially be tested in juvenile pig models for troubleshooting and establish flow and pressure parameters. The design will be done in consultation with Marlee Parker and engineering experts from University Health Network. This machine will offer point-of-care cardiac allograft reperfusion and assessment of both right and left ventricles.
The ex-vivo perfusion machine is a shining example of translational medical research, a novel homegrown innovation whose impact on child heart transplantation would be tangible and immediate – pending human trial results – at SickKids and children’s transplant centres around the world. The project has both clinical and research utility, allowing researchers to understand the limits of DCD donor heart viability and to test therapies that can improve donor heart function.