Predictive Accuracy of a Polygenic Risk Score for Postoperative Atrial Fibrillation After Cardiac Surgery.

Background - Postoperative atrial fibrillation (PoAF) remains a significant risk factor for increased morbidity and mortality after cardiac surgery. The ability to accurately identify patients at risk through clinical risk factors is limited. There is growing evidence that polygenic risk contributes significantly to PoAF, and incorporating measures of genetic risk could enhance prediction. Methods - A retrospective cohort study of 1,047 patients of white European ancestry who underwent either coronary artery bypass grafting (CABG) or valve surgery at a tertiary academic center, and were free from a history or persistent preoperative AF. The primary outcome was defined as PoAF based on postoperative ECG reports, medical record documentation, and changes in medication. The exposure was a polygenic risk score (PRS) comprising 2,746 SNPs previously associated with AF risk. The prediction of PoAF risk was assessed using measures of model discrimination, calibration, and net reclassification improvement (NRI). Results - A total of 259 patients (24.7%) developed PoAF. The PRS was significantly associated with a higher risk for PoAF (OR = 1.63 per standard deviation increase in PRS; 95% CI, 1.41-1.90). Addition of PRS to patient- and procedure-related predictors of PoAF significantly increased the C statistic from 0.742 to 0.782 (change in C statistic, 0.040; 95% CI, 0.021-0.060) while maintaining good calibration. The addition of the PRS to patient- and procedure-related predictors of postoperative AF improved model fit (likelihood ratio test p = 2.8 x 10-15) and significantly improved measures of reclassification (NRI, 0.158; 95% CI, 0.066- 0.274). Conclusions - The PRS for PoAF was associated with improved discrimination, calibration, and risk reclassification compared to conventional clinical predictors suggesting that a PoAF PRS may enhance risk prediction of PoAF in patients undergoing CABG or valve surgery.