Incidence and risk factors for rejection after conversion from calcineurin inhibitor to sirolimus-based immunosuppression in orthotopic heart transplant recipients

Sara S Inglis; Mohsin Abbas; Rabea Asleh; Armin Garmany; Byron H Smith; Sudhir Kushwaha; Naveen Pereira; Alfredo L Clavell; Mauricio A Villavicencio; Philip J Spencer; Richard C Daly; Atta Behfar; Andrew N Rosenbaum

doi:10.1016/j.healun.2024.12.014

Incidence and risk factors for rejection after conversion from calcineurin inhibitor to sirolimus-based immunosuppression in orthotopic heart transplant recipients

J Heart Lung Transplant. 2024 Dec 30:S1053-2498(24)02027-8. doi: 10.1016/j.healun.2024.12.014. Online ahead of print.

Authors

Affiliations

¹ Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester MN, 55905; Deparment of Cardiovascular Medicine, Mayo Clinic, Rochester MN, 55905.
² Deparment of Cardiovascular Medicine, Mayo Clinic, Rochester MN, 55905.
³ Graduate School of Biomedical Sciences, Alix School of Medicine, Medical Scientist Training Program, Mayo Clinic, Rochester MN, 55905.
⁴ Department of Biostatistics, Mayo Clinic, Rochester, MN, 55905.
⁵ Department of Cardiovascular Surgery, Mayo Clinic, Rochester MN, 55905.
⁶ Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester MN, 55905; Deparment of Cardiovascular Medicine, Mayo Clinic, Rochester MN, 55905. Electronic address: Rosenbaum.Andrew@mayo.edu.

PMID: 39743050
DOI: 10.1016/j.healun.2024.12.014

Abstract

Background: Although recommended in International Society for Heart and Lung Transplantation (ISHLT) guidelines, transition to mammalian targets of rapamycin (mTOR) inhibitors in heart transplant recipients is not routinely performed, in part due to perceived risk of rejection. This study sought to evaluate the incidence and risk factors for biopsy-proven, clinically relevant rejection following conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) immunosuppression.

Methods: A single center retrospective study was conducted of all consecutive adult patients who underwent orthotopic heart transplantation (OHT) and CNI-free SRL conversion from January 1999 to January 2023. All post-OHT biopsy data were obtained and graded per ISHLT criteria (antibody-mediated rejection [pAMR] or acute cellular rejection [ACR]). The primary endpoint was early rejection, defined as grade 2R ACR, pAMR 1, or greater, within 6 months after conversion.

Results: 317 patients (72% male, mean age 51.5 ± 12.6 years) were included. Median time to SRL conversion following OHT was 0.76 years (IQR 0.49, 1.42). Median time from conversion to rejection was 0.51 years (IQR 0.31, 1.05). 38 patients (12%) experienced early rejection. Following multivariate analysis, both timing to SRL conversion following OHT (OR 0.94 per month, 95% CI: 0.89-0.99, p-value = 0.0054) and age at transplantation (OR 0.96, 95% CI: 0.93-0.99, p-value = 0.0071) were independently associated with early rejection. Rejection following SRL conversion was not associated with increased risk of cardiac allograft vasculopathy (CAV) grade 2-3.

Conclusions: In a CNI-free SRL conversion protocol, both earlier SRL conversion following OHT and younger age at transplant are independently associated with early rejection, but rejection is not associated with a net increased risk of prognostically important CAV. Individualization of transition is necessary to mitigate risk, and these findings may aid in improvement of future conversion protocols.

Keywords: cardiac transplantation; mTOR inhibitor; rejection; sirolimus.