Deiodinase enzyme levels associated with acute allograft rejection after heart transplant

Introduction Thyroid function in the perioperative period of heart surgeries tend to get more substantial attention than ever before. The phenomenon that is hallmarked with low triiodothyronine (T3), low or normal thyroxine (T4), low or normal thyroid-stimulating hormone (TSH) and high reverse triiodothyronine (rT3) is called nonthyroidal illness syndrome (NTIS) or euthyroid sick syndrome. In spite of the well-known associations between NTIS and adverse outcomes during critical care, the pathogenesis is barely understood yet. Current study's aim to determine any possible connection between deiodinase enzyme levels any adverse outcomes in the perioperative period of heart transplant. Methods This prospective, single center study was performed on 283 heart transplanted patients at the Heart and Vascular Centre of Semmelweis University from 2012 to 2020. Demographic data, pre- and postoperative laboratory parameters, thyroid status, adverse events and applied mechanical circulatory support devices were recorded in our database. Type 2 deiodinase (DIO2) and type 3 deiodinase (DIO3) enzymes levels were measured with TaqMan qPCR and were normalized to hypoxanthine phosphoribosyl transferase (HPRT). For every qPCR reaction 30 ng of cDNA was used. Descriptive statistics, Spearman's correlation, Mann-Whitney U test, uni- and multivariate logistic regression were applied for the statistical analysis. Our study was approved by the IRB (65/2017). Results Out of 283 orthotopic heart transplanted patients 212 were male (74.9%) and 71 were female (25.1%). Donors’ median age was 42 years (IQR 25-75: 32-50), recipients’ median age was 54 years (IQR 25-75: 45-59) and median follow up time was 1521 days (IQR 25-75: 749-2270). 1-year mortality rate was 64 patients (22.6%). 34 patients (12.0%) suffered from acute allograft rejection in the first postoperative week, while in the first postoperative month it was 88 patients (31.1%). Acute allograft rejection was defined as per the International Society of Heart and Lung Transplantation (ISHLT) latest histopathologic findings criteria. DIO2 enzyme level were significantly lower in patient who suffered from acute rejection in the first postoperative week and month as well (p= 0.006 and p=0.019 respectively). In the multivariate logistic regression model DIO2 enzyme level measured in the first postoperative week was associated with significantly higher risk for acute rejection after heart transplant (OR: 0.775, 95% CI: 0.613-0.980, p=0.033). The multivariate logistic model calculated for the first postoperative month showed the same result regarding DIO2 enzyme level (OR: 0.832, 95% CI: 0.699-0.990, P= 0.038). Discussion Deiodinase enzyme levels after heart transplant are associated with acute allograft rejection in the first postoperative week and month. Thyroid function monitoring in the postoperative period after heart surgery might be essential based on our results.