# Association of Plasma BDNF Concentration and Val66Met Polymorphism with Postoperative Delirium After Cardiac Surgery Under General Anesthesia with Cardiopulmonary Bypass

## TL;DR

This study investigates whether brain-derived neurotrophic factor (BDNF) levels and a genetic variant (Val66Met) are linked to postoperative delirium in patients undergoing heart surgery with cardiopulmonary bypass.

## Contribution

The study evaluates the novel association between plasma BDNF concentrations and the Val66Met polymorphism with postoperative delirium in cardiac surgery patients.

## Key findings

- Postoperative delirium occurred in 19.6% of patients and was associated with prolonged hospitalization and reoperations.
- The BDNF Val66Met polymorphism was not linked to postoperative delirium, but carriers had higher plasma BDNF concentrations.
- Neurological complications remain a significant challenge in cardiac surgery, highlighting the need for better identification strategies.

## Abstract

Background/Objectives: Cardiac surgery, particularly procedures performed with cardiopulmonary bypass (CPB), carries a high risk of neurological complications, including postoperative delirium (POD), which affects 16–73% of patients and increases the likelihood of long-term cognitive impairment. Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in neuronal function, synaptic plasticity, and inflammatory regulation processes, including its Val66Met polymorphism, has been implicated as a potential predictor of POD. This study aimed to evaluate the relationship between perioperative plasma BDNF levels, the BDNF Val66Met polymorphism, and the incidence of POD in patients undergoing elective cardiac surgery with CPB. Methods: This prospective observational single-center study enrolled 287 adults scheduled for elective isolated coronary artery bypass grafting (CABG) with CPB, of whom 107 met all inclusion criteria for final analysis. Exclusion criteria included urgent surgery and pre-existing cognitive or psychiatric disorders. Preoperative evaluation included cognitive testing (MoCA), laboratory and biochemical analysis, and genotyping for BDNF Val66Met. Postoperatively, patients were assessed for POD using the CAM-ICU scale for the first three consecutive days. Cognitive function (using MoCA) and other neurological complications were evaluated during hospitalization, at 30-day and 12-month follow-up. Associations between biomarkers, genetic factors, and clinical outcomes were analyzed. Results: POD occurred in 19.6% of patients who were older, had higher EuroSCORE II, greater coronary disease burden, more frequent prior stroke and chronic kidney disease, and lower neutrophil counts. POD was significantly associated with prolonged hospital stay, need for continuous renal replacement therapy, and reoperation. The BDNF Val66Met polymorphism was present in 31.8% of patients but was not associated with POD, although carriers exhibited higher plasma BDNF concentrations across all time points. Conclusions: Perioperative plasma BDNF concentrations and the BDNF Val66Met polymorphism were not independently associated with the occurrence of POD in elective CABG patients. However, POD was significantly linked to prolonged hospitalization and reoperations. Neurological complications remain an important challenge in cardiac surgery, emphasizing the need for further research and early identification strategies to improve postoperative outcomes.