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Heart transplantation in perspective
1The University of Ottawa Heart Institute, Ontario, Canada.
Insights
Cardiac transplantation is a leading treatment for heart failure, but donor shortages and rejection necessitate alternatives like mechanical circulatory assist devices and xenotransplantation research.
Area of Science:
- Cardiology
- Transplantation immunology
- Biomedical engineering
Background:
- Heart disease is a major cause of death globally.
- Cardiac transplantation is a primary therapy for end-stage heart failure.
- Cyclosporine improved transplant success since 1981.
Observation:
- Limited donor hearts, ischemic time, and chronic rejection hinder transplantation.
- Over 2,000 circulatory assist devices (CADs) implanted, with 25% bridging to transplant.
- The University of Ottawa Heart Institute is developing an implantable electrohydraulic ventricular assist device (EVAD).
Findings:
- Xenotransplantation is being evaluated, but graft rejection remains a significant obstacle.
- Research focuses on donor heart preservation and novel immunosuppressants to increase organ availability.
- Mechanical circulatory assist devices offer alternatives for patients awaiting transplantation.
Implications:
- Continued research in xenotransplantation and mechanical support is crucial for future heart failure treatments.
- These alternative therapies aim to overcome donor organ limitations in cardiac replacement.
- Advancements promise expanded options for managing terminal cardiac failure.
Abstract:
Heart disease remains one of the leading causes of death in the western world. In the 35 years since the first human heart transplants, cardiac transplantation has become established as the therapeutic option of choice in the management of terminal cardiac failure. Since 1981, the introduction of cyclosporin for immunosuppression has dramatically increased cardiac transplantation. However, several obstacles limit further utilization, including limited availability of donor hearts, limited ischemic time tolerated by donor hearts, and chronic rejection. Research is underway into donor heart preservation and new immunosuppressant drugs in an effort to increase donor organ availability. Due to these constraints, alternative therapies are under development. More than 2,000 circulatory assist devices have been implanted with >25% used as a bridge to heart transplantation. The University of Ottawa Heart Institute began the first Canadian implantation of circulatory assist devices in 1986 and has implanted 23 total artificial hearts and 23 ventricular assist devices. The Heart Institute is also developing a totally implantable electrohydraulic ventricular assist device (EVAD) for long-term mechanical support outside the hospital. Another alternative being evaluated for clinical use is xenotransplantation. The major obstacle for widespread use of clinical xenotransplantation remains graft rejection, and fundamental research is ongoing to address hyperacute and delayed xenograft rejection. While cardiac transplantation is the most effective treatment of terminal heart failure, limited donor hearts compel us to rely on alternatives. In the future, the research underway on xenotransplantation and mechanical circulatory assist devices will provide new options for the clinical treatment of terminal cardiac failure.