Heart-After-Liver Transplantation Attenuates Rejection of Cardiac Allografts in Sensitized Patients

Richard C Daly; Andrew N Rosenbaum; Joseph A Dearani; Alfredo L Clavell; Naveen L Pereira; Barry A Boilson; Robert P Frantz; Atta Behfar; Shannon M Dunlay; Richard J Rodeheffer; John A Schirger; Timucin Taner; Manish J Gandhi; Julie K Heimbach; Charles B Rosen; Brooks S Edwards; Sudhir S Kushwaha

doi:10.1016/j.jacc.2021.01.013

Heart-After-Liver Transplantation Attenuates Rejection of Cardiac Allografts in Sensitized Patients

J Am Coll Cardiol. 2021 Mar 16;77(10):1331-1340. doi: 10.1016/j.jacc.2021.01.013.

Authors

Richard C Daly¹, Andrew N Rosenbaum², Joseph A Dearani¹, Alfredo L Clavell², Naveen L Pereira², Barry A Boilson², Robert P Frantz², Atta Behfar³, Shannon M Dunlay⁴, Richard J Rodeheffer², John A Schirger², Timucin Taner⁵, Manish J Gandhi⁶, Julie K Heimbach⁷, Charles B Rosen⁷, Brooks S Edwards², Sudhir S Kushwaha⁸

Affiliations

¹ Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.
² Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.
³ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA; VanCleve Cardiac Regenerative Medicine Program, Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA; Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
⁷ Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
⁸ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: Kushwaha.sudhir@mayo.edu.

PMID: 33706876
DOI: 10.1016/j.jacc.2021.01.013

Abstract

Background: In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation.

Objectives: The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection.

Methods: Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained.

Results: A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction.

Conclusions: A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Keywords: combined organ transplantation; heart transplantation; rejection; sensitization.

Publication types

Observational Study

MeSH terms

Adult
Clinical Protocols
Cohort Studies
Female
Graft Rejection / prevention & control*
Heart Transplantation*
Humans
Liver Transplantation*
Male
Middle Aged
Transplantation Immunology*