Xenotransplantation: Successful Pig-to-Human Heart Transplantation Highlights the X-Factor in the Treatment of Advanced Heart Failure

In January, 1964, Dr. James Hardy and his team at the University of Mississippi transplanted a chimpanzee’s heart into a 68-year-old man. The first cardiac transplant into a human was a xenotransplant, and it failed within hours. Rather than being celebrated as the first step towards successful cardiac transplantation in humans, Dr. Hardy was rebuked by both the press and his professional colleagues. Dr. Norman Shumway, a pioneer of cardiac transplantation, noted “perhaps the cardiac surgeon should pause while society becomes accustomed to resurrection of the mythological chimera.”1 Since then, there have been a few false starts with cardiac xenotransplantation, none surviving more than a week.2-4

Over six million people in the United States are living with heart failure, and approximately 300,000 progress annually to advanced heart failure, for which cardiac transplantation is a definitive treatment.5 Largely due to donor organ scarcity, only 3,817 cardiac transplants were performed in 2021.6 While the donor pool has been increased by novel treatments for hepatitis-C, adoption of extended donor criteria, donation after circulatory death, and ex-vivo cardiac perfusion, their maximal effect on the total donor pool pales in comparison to the possibilities afforded by mastering xenotransplantation.7,8

‘A Medical Breakthrough’

In a medical breakthrough, the first genetically-engineered porcine heart was transplanted into a 57-year-old patient at the University of Maryland on January 7, 2021 by Dr. Bartley Griffith and his surgical team. The patient is currently awake, breathing on his own, and successfully weaned off of mechanical circulatory support.

According to Dr. Susan Joseph, Medical Director of the University of Maryland Advanced Heart Failure and Cardiac Transplant program, “the hurdles that had to be overcome to make this colossal achievement feasible were the results of decades of research,” much of which occurred at the University’s Cardiac Xenotransplantation program led by Drs. Griffith and Muhammad Mohiuddin. She explained these innovations included genetic modification of the donor pig to address organ rejection risk, as well as an accelerated form of cardiac hypertrophy seen in previous porcine donor-heart trials. Despite the advances in genetic engineering, immunosuppressive therapy is still needed, including, according to Dr. Joseph, a “unique combination of established and investigational medications used for induction.”

Dr. Shumway famously said “xenotransplantation is in the future of heart transplantation, and always will be.”2 This technically successful xenotransplant is only the beginning of a long road, both for the patient and the field, but for the cautiously optimistic, the future may quickly be arriving.

References

  1. McRae D. Every Second Counts: The Race to Transplant the First Human Heart. New York: G.P. Putnam’s Sons, 2006.
  2. Cooper DK. A brief history of cross-species organ transplantation. Proc (Bayl Univ Med Cent). 2012;25:49-57.
  3. Barnard CN, Wolpowitz A, Losman JG. Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. S Afr Med J. 1977;52:1035-8.
  4. Mudur G. Indian surgeon challenges ban on xenotransplantation. BMJ 1999;318:79.
  5. Morris AA, Khazanie P, Drazner MH et al. Guidance for Timely and Appropriate Referral of Patients With Advanced Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2021;144:e238-e250.
  6. Network OPaT. Heart Transplants by Donor Type. National Data.
  7. Kittleson MM, Kobashigawa JA. Cardiac Transplantation: Current Outcomes and Contemporary Controversies. JACC Heart Fail. 2017;5:857-868.
  8. Schlendorf KH, Zalawadiya S, Shah AS et al. Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C. JAMA Cardiol. 2020;5:167-174.