RELEVANCE OF DEIODINASE ENZYMES IN HEART TRANSPLANT – PRELIMINARY STUDY

Abstract

<h3>Objective</h3> The hypothalamic-pituitary-thyroid (HPT) axis plays a critical role in the regulation of metabolism throughout the neuroendocrine system. The low triiodothyronine (T3) syndrome appears in several critical conditions that require intensive care, such as heart transplant (HTx) which is the gold standard therapeutic intervention for patients with end-stage chronic heart failure. Low T3 syndrome is hallmarked by reduced serum thyroid hormone (TH) levels; missing or reduced response of the HPT axis; and tissue-specific changes of the expression of deiodinase enzymes, catalyzing TH hormone metabolism. Current research aimed to study the interaction between cardiac deiodinase expression and adverse outcomes after HTx. <h3>Design and Method</h3> This prospective, single center study was approved by the IRB (65/2017). Patients who underwent heart transplant at the Heart and Vascular Centre of Semmelweis University between 2012 and 2020 were enrolled in current research. Demographic and perioperative laboratory parameters, thyroid disorders and adverse outcomes were recorded in our database. Expression of the TH activating Deiodinase 2 (DIO2) and TH inactivating Deiodinase 3 (DIO3) enzymes was measured with TaqMan qPCR in cardiac tissue samples and were normalized to hypoxanthine phosphoribosyl transferase (HPRT). cDNA content of samples was measured by Qubit, and 30 ng of cDNA was used in each qPCR reaction. Descriptive statistics, Spearman's correlation and Mann-Whitney U test were applied for the statistical analysis. <h3>Results</h3> The final analysis was performed on 294 patients, of whom 77 were female (26.2%) and 217 were male (73.8%). The median age of donors was 54 years (IQR 25-75: 45-59), while the median follow-up was 1223 days (IQR 25-75: 399-1990). Prior to surgery, 53 patients (18.0%) had subclinical serum TH levels, of whom 37 (12.6%) were on TH replacement. Patients required postoperative mechanical circulation support (n: 50; 17.0%), underwent rejection (n: 47; 16.0%), and reoperation (n: 34; 11.6%) had significantly lower DIO2 and DIO3 expression (respectively p: 0.016; 0.001; 0.044). However, cardiac DIO2 expression was significantly higher in patients with postoperative acute kidney injury (n: 75; 25.5%) (p: 0.033). <h3>Conclusions</h3> Our results emphasize the importance of cardiac TH metabolism during the perioperative period of heart transplant as DIO2 and DIO3 enzymes expressions may predict the occurrence of some complications after heart transplant. Unidirectional changes of the TH activating and inactivating deiodinases during the perioperative period of heart transplant do not suggest a coordinated cellular effort to shift TH signaling in the cardiac tissue except in patients with postoperative acute kidney injury.for observation.