ISHLT Provides Updates in Xenografting in Patients with Cardiac Diseases, With Anu Lala, MD

On February 20, 2026, the International Society for Heart and Lung Transplantation (ISHLT) released a consensus statement aiming to redefine the challenges and outline recommendations for moving forward in the field of xenotransplantation for end-stage cardiac diseases.1

This consensus statement builds on an existing document published in 2000, which highlighted the urgent need for donor organs for use in patients with cardiac and pulmonary diseases. To counter this, the authors indicated a potentially unlimited supply of hearts and lungs via pig organs. Of course, the document also acknowledged the natural barriers of antibody-mediated mechanisms in both the pig heart and the human recipient, which resulted in rejection after transplantation into non-human primates in earlier trials.2

The 2026 consensus statement builds upon recent research, including the successful performance of 2 clinical heart xenotransplant cases. However, many of the challenges highlighted in the 2000 statement still linger 26 years later. As a result, the ISHLT committee behind the current statement designed it as a “living blueprint,” leaving it open for further editing and sculpting as the procedure is duplicated and thornier issues, such as ethical concerns, are worked out over time.1

“This was a real tour de force,” Anuradha Lala, MD, professor of medicine, cardiology, and population health, director of the ACGME Fellowship in Advanced Heart Failure and Transplant, and Director of the Heart Failure Clinical Trials program at Mount Sinai Hospital, told HCPLive in an exclusive interview. “This document matters now because the field needed a living blueprint. We’ve had 2 human pig heart transplants, so we know that xenografts can function, but we also know that they can fail. We’re trying to learn why, and it’s an evolving process.”

The 2 successful xenografts lasted 60 and 40 days, respectively. The first, a 57-year-old man with advanced heart failure with non-ischemic cardiomyopathy, underwent a challenging, yet ultimately successful, operation. Weeks 2 through 5 exhibited a stable trajectory, after which point the patient became unstable, showing hypotension, abdominal distension, and low output syndrome with low mixed venous saturation.1

The second graft was more challenging; the patient, a 58-year-old man, suffered cardiac arrest prior to transplantation and developed renal dysfunction. By day 13, endomyocardial biopsy revealed antibody-mediated rejection (AMR), and by day 31, the patient required mechanical circulatory support following graft failure. Care was withdrawn on day 40.1

These operations, although ultimately resulting in graft failure, proved greatly informative for clinicians, providing further data regarding immunosuppression and monitoring following xenotransplantation. The consensus statement also makes note of emerging techniques and tools, including gene expression profiling and donor-derived cell-free DNA in blood, to survey immunological challenges. However, they also acknowledge that these are largely underexplored in xenotransplantation. These, among other advancing mechanisms, are recommended for further study.1

“People are dying on the wait list every day, and the reason, of course, is because we’re constrained by donor hearts in a way that no surgical innovation, including LVAD optimization, has been able to overcome,” Lala said. “Xenotransplantation, which at some previous point might have seemed like science fiction, is a real clinical necessity that we’re working towards in a very thoughtful, disciplined, and now structured way.”

Editors’ Note: Lala reports disclosures with Abiomed, AstraZeneca, Merck & Co., Novo Nordisk, Sequana, Bayer, and others.

References

1. 1: Mehra MR, Mohiuddin MM, Reichart B, et al. The 2026 International Society for Heart and Lung Transplantation Consensus Statement on clinical cardiac xenotransplantation. J Heart Lung Transplant. Published online January 30, 2026. doi:10.1016/j.healun.2025.12.012

2. 2: Cooper DKC, Keogh AM, Brink J, et al. Report of the Xenotransplantation Advisory Committee of the International Society for Heart and Lung Transplantation: The Journal of Heart and Lung Transplantation. 2000;19(12):1125-1165. doi:10.1016/s1053-2498(00)00224-2