- The first clinical trials of pig-to-human heart transplantation could be launched within the next five years
- For cardiac xenotransplantation to be ethically justified, its risks must be outweighed by the risks of current state-of-the-art treatment options such as ventricular assist devices (VAD)
- Proposed trial candidates include patients with a high immunologic risk associated with allotransplant, a contraindication to VAD implantation, complex adult congenital heart disease or severe biventricular failure without established end-organ failure
To address the current shortfall of donor hearts for transplantation, scientists are investigating the use of genetically modified pigs as a source of hearts. If cardiac xenotransplantation is successful, it may also benefit many patients who are currently not offered heart transplantation or whose condition deteriorates while they're on the waitlist.
Judging from recent progress in pig-to–nonhuman primate heart transplantation, Richard N. Pierson III, MD, cardiac surgeon, David A. D'Alessandro, MD, surgical director of Heart Transplantation at Massachusetts General Hospital, and colleagues expect clinical trials of cardiac xenotransplantation to be started within the next five years. In an opinion piece in the American Journal of Transplantation, they propose categories of patients whom they believe would meet ethical standards for participation in initial trials.
In line with guidance from the U.S. Food and Drug Administration, patients should be eligible for a clinical trial of cardiac xenotransplantation if they meet both of the following criteria:
- Medically eligible for, and likely to benefit from, access to effective heart replacement therapy
- Significantly disadvantaged and effectively excluded from being offered a human organ
Internationally accepted ethics guidelines discourage the inclusion of children in first-in-human trials, particularly for high-risk interventions.
Adults with the following characteristics who are awaiting heart transplantation would satisfy the principle of clinical equipoise (genuine uncertainty about which treatment is better) for participating in a pioneering trial of xenotransplantation:
- A high immunologic risk associated with allotransplant—a rapid progression of cardiac allograft vasculopathy or myocardial fibrosis; broadly reactive, high-titer antibody against human leukocyte antigens
- An absolute or relative contraindication to implantation of a ventricular assist device (VAD)
- Complex adult congenital heart disease—single-ventricle physiology with progressive arrythmias or heart failure; falling left-to-right shunt
- Severe biventricular failure without established end-organ failure—severe right ventricular failure in the context of left ventricular failure (candidate for BiVAD); candidate for total artificial heart
Proposed Exclusion Criteria
Initially, at least, trials of cardiac xenografting should exclude patients with:
- Acute cardiac decompensation
- One or more comorbidities likely to limit quality of life or duration of survival
- Recent malignancy or chronic infection
- Anatomy or surgical history that might make the procedure unfeasible
- Active or unstable psychiatric disease
- Poor compliance with other health care regimens
- Inadequate caregiver and social supports
Failure of xenotransplantation to benefit patients significantly would confound efforts to fairly evaluate its safety and efficacy, as well as undermine public confidence in the field.
Learn more about the Heart Failure and Cardiac Transplantation Program at Mass General
Refer a patient to the Corrigan Minehan Heart Center