Wan CH, Zhou BY, Guan YL. Cardiac xenotransplantation: From imagination to achievable practice. World J Cardiol 2026; 18(8): 125199 [DOI: 10.4330/wjc.125199]
Corresponding Author of This Article
Yu-Long Guan, MD, Professor, Department of Extracorporeal Circulation, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, China. guanyulong2014@163.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
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review-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Aug 26, 2026; 18(8): 125199 Published online Aug 26, 2026. doi: 10.4330/wjc.125199
Cardiac xenotransplantation: From imagination to achievable practice
Cai-Hong Wan, Bo-Yi Zhou, Yu-Long Guan
Cai-Hong Wan, Department of Extracorporeal Circulation and Mechanical Circulation Assistance, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
Bo-Yi Zhou, Yu-Long Guan, Department of Extracorporeal Circulation, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
Co-first authors: Cai-Hong Wan and Bo-Yi Zhou.
Author contributions: Wan CH and Zhou BY drafted the article and contributed equally to this work, have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper; Guan YL performed the final reviewing and editing; all authors read and approved the final manuscript.
AI contribution statement: During the preparation of this work the authors used DeepSeek-V3.1 in order to check spelling and grammar. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
Conflict-of-interest statement: The authors declare no conflict of interest.
Corresponding author: Yu-Long Guan, MD, Professor, Department of Extracorporeal Circulation, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, China. guanyulong2014@163.com
Received: July 2, 2026 Revised: July 30, 2026 Accepted: August 20, 2026 Published online: August 26, 2026 Processing time: 56 Days and 21.2 Hours
Abstract
Allogeneic heart transplantation and durable mechanical circulatory support remain the standard treatments for advanced refractory heart failure, but donor-heart scarcity and device-related complications leave many patients without viable options. Driven by advances in gene editing, immunosuppression, and donor-organ preservation, cardiac xenotransplantation (XTx) has progressed rapidly, culminating in the landmark first-in-human compassionate-use application in 2022. This minireview critically summarizes the development of clinical cardiac XTx. We performed a narrative literature search of PubMed/MEDLINE, Web of Science, and Google Scholar from inception to 2026 using terms including cardiac XTx, gene-edited pig, immunosuppression, and xenograft, prioritizing landmark preclinical studies, human cases, and regulatory or ethical publications, and stratifying the evidence as in vitro or mechanistic studies, non-human primate (NHP) survival studies, living compassionate-use recipients, and deceased-recipient models. The principal findings are: Multigene-edited pig hearts combined with costimulation-blockade immunosuppression have achieved graft survival beyond one year in NHP; two living compassionate-use recipients (2022 and 2023) demonstrated proof-of-concept xenograft function for 40-60 days but died of multifactorial graft failure involving antibody-mediated injury, porcine cytomegalovirus reactivation, and diastolic dysfunction; and deceased-recipient studies confirmed short-term feasibility without hyperacute rejection. Cardiac XTx remains experimental but represents a promising proof of concept whose translation to clinical trials requires resolution of immunologic injury, infectious risk and graft overgrowth.
Core Tip: Cardiac xenotransplantation has advanced from the failed animal-heart attempts of 1964-1984 to two landmark first-in-human compassionate-use transplants of 10-gene-edited pig hearts in 2022 and 2023. Although both recipients died within 40-60 days, these proof-of-concept cases defined the key remaining barriers-antibody-mediated injury, porcine viral reactivation, and diastolic dysfunction-that must be resolved before gene-edited pig hearts may be explored in the further clinical trials and act as one of reliable and effective means for the treatment of end-stage heart failure.
