Background:
Postoperative arrhythmias, particularly atrial fibrillation, are frequent and significant complications following major cardiac surgery, leading to increased morbidity and healthcare costs. While the "brain-heart axis" suggests that perioperative neurological injury can promote an arrhythmogenic substrate through neuroinflammatory pathways, the predictive value of blood-based biomarkers of neuronal cell injury remains uninvestigated. We aim to evaluate if elevated levels of neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), Neurofilament Light Chain (NfL), and Tau protein, as well as their perioperative increase, are associated with the development of postoperative arrhythmias.
Methods and results:
We evaluated patients enrolled in a prospective cohort study targeting individuals undergoing elective on-pump major cardiac surgery. Inclusion in this analysis required preoperative and postoperative (day 1) blood samples. Biomarker quantification (GFAP, NfL, and Tau) was performed using the ultra-sensitive Simoa platform. NSE concentrations were determined using the BRAHMS NSE KRYPTOR assay. Information on arrhythmic events after surgery within hospital stay were taken from the routine medical documentation. Statistical models were used to evaluate the association between biomarker levels and arrhythmic events.
Mean age of the evaluated 46 patients (12 women) was 72.8 years (SD 5.2 years), the arrhythmic endpoint was observed in 18 individuals (39.1%). 63% had arterial hypertension, 10.9% were diabetic, 82.6% had a known dyslipidemia, and 23.9% had been previously diagnosed with atrial fibrillation. All evaluated biomarkers of neuronal damage showed an increase from median baseline values to measurements on day 1 after surgery with GFAP from 121.84 (IQR 90.85-173.09) to 226.64 (IQR 168.23-351.93) pg/mL (p<0.001), with NfL from 11.82 (IQR 9.38-14.77) to 14.44 (IQR 12.18-19.41) pg/mL (p=0.005), with Tau from 3.53 (IQR 2.71-4.34) to 7.59 (IQR 6.40-11.54) pg/mL (p<0.001) and with NSE from 12.84 (IQR 11.45-14.77) to 24.24 (IQR 19.69-25.87) ng/mL (p<0.001). Regarding the occurrence of postoperative arrhythmia, only Tau levels showed a significant difference comparing patients with or without the complications. For example, Tau levels on day 1 in patients with postoperative arhythmias were 11.7 (IQR 7.7-13.7) vs. 6.9 (IQR 5.7-7.8) pg/mL (p=0.002). Using Tau concentrations on day 1, baseline or as delta Tau to predict postoperative arrhythmia yielded an area under the receiver operator characteristic curve (AUROC) of 0.774 (0.62-0.93), 0.744 (0.598-0.89) and 0.692 (0.529-0.86). The combination of these three Tau values was associated with an AUROC of 0.78 (0.641-0.92) to predict postoperative arrhythmia.
Conclusions:
Data from our pilot study shows that biomarkers of neuronal cell injury are significantly elevated on day 1 after major cardiac surgery. Increases in Tau protein levels are associated with the development of arrhythmias following major cardiac surgery. Further evaluations in larger cohorts are needed to describe the potential predictive value of Tau for identifying patients at risk for postoperative complications such as arrhythmias.
