Severe primary graft dysfunction of the heart transplant is associated with increased plasma and intragraft proinflammatory cytokine expression

INTRODUCTION: Heart transplant results have constantly improved but primary left ventricle graft dysfunction (LV-PGD) remains a devastating complication early after transplantation. Donor and recipient systemic inflammatory response may be involved in immune activation of the transplant, and LV-PGD development. Here, we investigated donor and recipient plasma and intragraft cytokine profiles preoperatively and during LV-PGD and searched for predictive markers for LV-PGD.METHODS: Donor and recipient plasma samples (n = 74) and myocardial biopsies of heart transplants (n = 64) were analyzed. Plasma and intragraft cytokine levels were determined by multiplexed and next-generation sequencing platforms, respectively. The development of LV-PGD during the first 24 hours, and graft function and mortality up to 1 year after transplantation, were examined.RESULTS: Severe LV-PGD, but not mild or moderate LV-PGD, was significantly associated with early mortality, plasma high-sensitivity troponin elevation, and an increase in intragraft and plasma proin-flammatory cytokines during reperfusion. Preoperative donor and recipient plasma cytokine levels failed to predict LV-PGD. Cytokine network analysis identified interleukins-6,-8,-10, and-18 as key players during reperfusion. Prolonged cold and total ischemia time, and increased need for red blood cell transfusions during operation were identified as clinical risk factors for severe LV-PGD.CONCLUSIONS: Severe LV-PGD was associated with a poor clinical outcome. Donor and recipient plasma cytokine profile failed to predict LV-PGD, but severe LV-PGD was associated with an increase in post-reperfusion intragraft and recipient plasma proinflammatory cytokines. Identified key cytokines may be potential therapeutic targets to improve early and long-term outcomes after heart transplantation. J Heart Lung Transplant 2023;42:807-818 (c) 2023 International Society for Heart and Lung Transplantation. All rights reserved.

Automated summary

Heart transplant is a successful treatment, but primary left ventricle graft dysfunction (LV-PGD) can still occur, leading to poor outcomes. This study investigated the cytokine profiles in donors and recipients before and during LV-PGD, and identified potential markers for LV-PGD.