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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

SEVERE PRIMARY GRAFT DYSFUNCTION OF THE HEART TRANSPLANT IS ASSOCIATED WITH INCREASED PLASMA AND INTRAGRAFT PROINFLAMMATORY CYTOKINE EXPRESSION

Published:January 18, 2023DOI:https://doi.org/10.1016/j.healun.2023.01.005

      ABSTRACT

      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 proinflammatory 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.

      KEYWORDS

      ABBREVIATIONS:

      CKMBm (creatine kinase MB isoenzyme mass), hsCRP (high-sensitivity C-reactive protein), HTx (heart transplantation), IL (interleukin), LV (left ventricular), MAP (mean arterial pressure), NT-proBNP (N-terminal pro b-type natriuretic peptide), PGD (primary graft dysfunction), RV (right ventricular), SGD (secondary graft dysfunction), TnT (troponin T)
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