Does Xenotransplantation Offer a Large Benefit for Human Patients?

Current Status of Cardiac Xenotransplantation: Report of a Workshop of the German Heart Transplant Centers, Martinsried, March 3, 2023

We read with interest the report from Schmoeckel et al regarding the March 3, 2023 Workshop of the German Heart Transplant Centers.[1] Within the report, Schmoeckel et al mention the ethical requirement that xenotransplantation offer recipients a favorable risk–benefit outcome. To our surprise, they write “a heart [xenotransplantation] can be expected to have a rather large benefit with sufficient certainty for patients in terminal heart failure” and that xenozoonotic transmission “does not appear to represent an obstacle from an ethical perspective.” Our concern is that, in light of the two recent cardiac xenotransplantations, the risk–benefit analysis remains contested and not so clearly favorable.

First, the initial cardiac xenograft recipient in early 2022, Mr. Bennett, died 60 days post-transplant and had acquired a porcine cytomegalovirus from the graft, which may have contributed to the graft's failure.[2] The second cardiac xenograft recipient, Mr. Faucette, died just shy of 6 weeks post-transplant and the cause of his death has yet to be announced, though the heart showed signs of rejection. In short, the conclusiveness of heart xenotransplantation being “expected to have a rather large benefit with sufficient certainty for patients in terminal heart failure” seems far from a foregone conclusion. While we remain hopeful that one day cardiac xenotransplantation will indeed be a viable clinical alternative to allotransplantation, presenting “sufficient certainty” for patients in need, this still seems to be a way off. Even should formal clinical trials begin soon, clinical equipoise will not exist for some time.

Second, the authors state that, “With appropriate sensitive screening for xenogeneic infections, the potential harm for third parties, hospital staff and close relatives, does not appear to represent an obstacle from an ethical perspective.” Screening for xenogeneic infections requires the availability and reliability of sensitive microbiologic assays, some of which are available and others are not.[3] Yet, an ethical issue that has received scant attention in the literature is risk to third parties or so-called bystanders. Not only are appropriate screening measures needed but also education of persons who are plausibly at heightened risk of acquiring a novel xenozoonosis from the xenograft recipient due to proximity and frequency of contact is required. This could be family members, sexual partners, caregivers, and many others. Screening for infectious disease in the xenograft recipient may be straightforward if bio-surveillance is mandated (though this in itself is controversial), yet it is not so direct for bystanders. Thoughtful consideration must be given on how to educate bystanders and how screening for xenozoonosis might be accomplished should infection be suspected, followed by necessary quarantine should infection be confirmed. The ethical matters, then, are far more complex than the authors lead on.

While we remain optimistic about the future of xenotransplantation, a more matter-of-fact analysis of the current situation is needed in light of the fact that in the only two genetically modified porcine heart-to-human transplantations that have been conducted, the patients rapidly declined under uncertain circumstances.

Publication History

Received: 03 January 2024

Accepted: 09 January 2024

Accepted Manuscript online:
10 January 2024

Article published online:
13 February 2024

• References

• 1 Schmoeckel DM, Längin M, Reichart B. et al. Current status of cardiac xenotransplantation. Thorac Cardiovasc Surg 2023; (e-pub ahead of print). DOI: 10.1055/a-2235-8854.
• 2 Cooper DKC, Yamamoto T, Hara H, Pierson III RN. The first clinical pig heart transplant: was IVIg or pig cytomegalovirus detrimental to the outcome?. Xenotransplantation 2022; 29 (04) e12771
• 3 Fishman JA. Risks of infectious disease in xenotransplantation. N Engl J Med 2022; 387 (24) 2258-2267