Background: The first clinical genetically-engineered pig heart transplant has stimulated consideration of which patients might be medically and ethically appropriate to enroll in the initial clinical trials. Beyond exceptional ‘compassionate use’ applications, as in the University of Maryland case, which patients might be selected for formal ‘qualifying’ trials of ‘destination’ or  ‘bridging’ heart xenotransplantation?

Approach and Results: Patients eligible for a heart allograft and in whom mechanical circulatory support is contraindicated or associated with a high risk of mortality or morbid complications, such as presence of a mechanical valve prosthesis, restrictive or hypertrophic cardiomyopathy, and refractory ventricular arrhythmias, are at high risk of dying before transplant, and might be eligible for either a ‘bridging’ or ‘destination’ trial.  Patients with high titers of panel-reactive anti-HLA antibodies, including prior allotransplant recipients with graft vasculopathy, are at high risk of sudden death, experience long waiting times and inferior post-allograft survival; those without antibodies that cross-react with pig cells might expect better survival after a successful heart xenograft than after desensitization to enable a heart allograft. Infants and children with complex CHD have limited access to allotransplantation due to the scarcity of size-matched donor organs. In these patients the results of mechanical support are poor, and both survival and quality of life after multiple staged surgical reconstructive procedures remain limited, particularly for those relying upon univentricular ‘Fontan’ physiology. A genetically-engineered pig heart could be used as a life-supporting ‘bridge’ for a clinically deteriorating infant or child until a heart from a size-appropriate deceased human donor can be obtained. Pediatric or adult patients presenting in extremis and unable to participate, with their caregivers, in a complete, robust informed consent process would be inappropriate to enroll on ethical grounds. Patients whose prognosis is poor based on risk factors not directly related to their heart pathology, such as frailty or malignancy, that would disqualify them as heart allograft candidates should also be avoided, as this approach is likely to yield poor outcomes and undermine public and peer support for xenotransplantation.

Conclusion: We propose that patients meeting these inclusion and exclusion criteria are appropriate to consider for enrollment in initial heart xenograft clinical trials.