Improving the Prediction of Postoperative Atrial Fibrillation After Cardiac Surgery Using Multiple Pathophysiological Biomarkers: A Prospective Double-Centre Study

Background: Postoperative atrial fibrillation (POAF) is a common and serious complication after cardiac surgery. Existing clinical prediction models show limited discriminative ability. We hypothesize that incorporating biomarkers that reflect key pathophysiological pathways of POAF can enhance preoperative risk stratification. Methods Adult cardiac surgery patients without a history of atrial fibrillation from the BIGPROMISE cohort - a prospective, observational, two-centre perioperative biobank study - were included to investigate whether biomarkers of myocardial injury, systemic inflammation, haematological status, metabolic and neuroendocrine dysregulation improve prediction of new-onset POAF compared to an established clinical model, the POAF-Score. We evaluated the incremental value of a 13-biomarker panel added to the POAF-Score using multivariable logistic regression with shrinkage (lasso), assessing model discrimination, calibration, reclassification, and net clinical benefit. Results Among 959 cardiac surgery patients, POAF occurred in 35% (n=339). Inflammatory, metabolic, and neuro-endocrine biomarkers remained independently associated with POAF after applying lasso regression. Adding these biomarkers to the POAF-Score improved discrimination, with the C-statistic increasing from 0.60 (95% CI: 0.60–0.60) to 0.63 (95% CI: 0.63–0.64; P< 0.01). Calibration was good for both models. At a threshold of 40% for high risk of POAF, the addition of biomarkers correctly reclassified 16% of patients with POAF as high risk. However, only 2% of the patients without POAF were reclassified as low risk, while 13% were incorrectly reclassified as high risk, resulting in a net reclassification index of 0.05. Conclusions Adding pathophysiological biomarkers significantly improves the performance of an established risk model for POAF after cardiac surgery, although the incremental clinical benefit is small.